Biologic Drugs: Black Is The New Orange

Biologic Drugs
Black is the New Orange
SIMON BAKER BIOPHARMACEUTICALS 15 OCTOBER 2021

About the team
Simon Baker
Prior to joining Redburn, Simon co-headed pharmaceutical research
at Exane BNP Paribas, having previously followed the sector at
Occitan Capital, Credit Suisse and Lehman Brothers. Simon holds a
First Class degree in Chemistry and PhD in Organic Chemistry, both
from Imperial College London. He is a CFA Charterholder.
T +44 20 7000 2072

E simon.baker@redburn.com
Charles Pitman
Charles joined Redburn through its internship programme and
worked in the Aerospace & Defence sector before joining the
Pharmaceuticals Team. He holds a First Class Masters in Mathematics
from Durham University. Charles is a CFA Charterholder.
T +44 20 7000 2089

E charles.pitman@redburn.com
Biologic Drugs / 15 October 2021
Biologic Drugs
Black is the New Orange
One cannot value a pharma company without knowing when generic or

biosimilar competition for its drugs is likely. For large, biologic molecules,
that is far from trivial due to the absence of a central source of information
akin to that for their small molecule counterparts. In this report, we provide
that missing information, for biologic drugs approved in the US since 2000.
By analysing c800,000 patent dossiers, we have managed to fill most of the
gaps in existing Patent Office data, completing the rest by our own searches.
From this ‘key patent’ starting point, we then consider other potentially
relevant IP, since biologics are often protected by multiple patents. This
is presented by company for each drug, along with information on the
individual products’ characteristics and approved indications.
Taken together with our small molecule assumptions, we map out the expiry
profile for our European universe in this decade and beyond, indicating the
revenues at risk by year, region and drug. We see a generally benign outlook
to 2025, with a small number of large impact events thereafter until 2030.
Among our preferred names, the profile for AstraZeneca (Buy) looks
encouraging, as does the outlook for GlaxoSmithKline (Buy), particularly
before 2027. Sanofi (Neutral) has very little risk from generics or biosimilars
this decade, but nor does it have notable growth.
Simon Baker
+44 20 7000 2072
simon.baker@redburn.com
Important note: see regulatory disclosures on page 192 of this report. 3

Contents
Contents
The idea .......................................................................................................................... 5

01/ Patent and exclusivity data ................................................................................... 17
How we assembled the data ............................................................................................................................18
4 Important note: see regulatory disclosures on page 192 of this report.

The idea
The idea
In order to value a drug, and therefore a pharma company, the launch date and
generic competition entry point are crucial considerations. For small molecule drugs,
such as statins, the expected generic entry date in the key US market is readily
obtained from the Food and Drug Administration’s (FDA) Orange Book. For large
molecules, such as antibodies, the task is much harder because patent information is
not compiled for such drugs. This report seeks to fill that gap. In doing so, a number of
our assumptions have been updated to reflect the information we have obtained from
multiple sources.
The proportion of biologics drugs (proteins and antibodies) has risen in recent years
(Fig 1). That is good news because the erosion cycle of such drugs is considerably less
aggressive than for small molecule therapeutics. However, it does raise a problem:
when exactly will they erode? This is not mere intellectual curiosity, for that date is a
critical part of the valuation of the drug and hence its owner.
Fig 1: Biologics as a proportion of global pharma sales, 2010-26E

50%
45%
40%
Share of global pharma sales
35%
30%
25%
20%
15%
10%
5%
0%
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026
New modalities Vaccines Monoclonal antibodies Recombinant proteins Other
Source: Redburn, Evaluate Pharma
Erosion by generic competition begins, often immediately, following the expiry of the
drug’s patents. Determining this in the US is straightforward. Since the 1980s, the
FDA’s ‘Approved Drug Products with Therapeutic Equivalence Evaluations’ has
provided the answer. Better known by the colour of its cover, the Orange Book lists all
the relevant in-force patents for small molecules, along with their expiry dates. While
similarly comprehensive data do not exist for the rest of the world, a reasonable
estimate can be made based on the US situation and a mosaic of other sources.
For biologic drugs, no such guide exists in the US or elsewhere. The level of disclosure
varies by company. Some are very reticent to disclose any information on commercial

The idea
grounds; others give the years of lost patent protection for some products, but we are
unaware of any company that provides detailed information on entire portfolios.
In order to value individual drugs and thus whole companies, we have long needed
this information and have struggled in many cases to get good answers. Rules of
thumb abound, giving a set number of years in various markets from launch to
biosimilar entry, but that often misrepresents the true picture. We therefore set out to
fill this gap by analysing the patent protection of all biologic drugs approved in the US
since 2000.
What we found
Looking at the specific findings of this report, namely US biologics alone, we see
relatively modest sales that will be exposed to potential biosimilar competition before
2025 across our European universe (Fig 2). The only notable exception is UCB’s
Cimzia in 2024.
Fig 2: US sales of biologic drugs in the year of lost exclusivity

Company name
AstraZeneca $1,287m $1,800m $900m $2,700m $59m $7,000m
GlaxoSmithKline $1,139m $1,261m $308m $342m
Merck KGaA $949m $2,334m
Novartis $513m $4,080m $500m $1,500m
Novo Nordisk $2,817m $400m $22m
Roche $2,982m $1,247m $7,384m $407m $8,293m $909m
Sanofi $952m $165m $250m $8,107m $337m
UCB $1,632m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036
Expiry Year
Source: Redburn
For 2025, we start to see more meaningful impacts, such as Roche’s Perjeta and
AstraZeneca’s Soliris, but for the remainder of the decade, we would note only one
major expiry, that of Roche’s Ocrevus in 2028. We would also emphasise that the dates
above represent a conservative view of biosimilar timing. With broad patent estates in
many cases, the actual point of entry could be delayed. Perjeta, for example, has
potentially relevant IP until 2038 that could thwart biosimilar entry.
Also, as a general principle, we have based expected biosimilar competition on patent

expiry rather than on expiration of data exclusivity. The Biologics Price Competition
and Innovation Act of 2009 (BPCIA) grants 12 years of exclusivity from approval for
novel biologic drugs. In the majority of cases, this expires before the relevant patent,
but not all. Nevertheless, the somewhat tardy determination of eligibility by the FDA
for this exclusivity (essentially confining itself so far to litigated cases) means that we
have not used the exclusivity expiry date if farther out but list them in Chapter 1.
Using the US patent landscape as a basis for global protection, along with specific data
where available, we see a broadly similar cadence of potential biosimilar entry, with
limited major threats this decade (Fig 3).

The idea
Fig 3: Global sales of biologic drugs in the year of lost exclusivity, split by region
Company Region
AstraZeneca EM $160m $85m $200m $449m $250m $500m
Europe $879m $965m $1,737m $800m $1,000m
ROW $792m $250m $500m $855m $1,200m $300m
USA $1,287m $1,800m $900m $2,700m $59m $7,000m
GSK Europe $455m $121m $103m $205m
ROW $445m $129m $68m $205m
USA $1,139m $1,261m $308m $342m
Ipsen Worldwide $31m
Merck KGaA EM $225m $227m
Europe $1,474m
ROW $656m $160m
USA $949m $2,334m
Novartis ROW $643m $2,800m $500m $800m $1,100m
USA $513m $4,080m $500m $1,500m
Novo Nordisk EM $194m $22m
Europe $1,245m $460m $15m
USA $2,817m $400m $22m
Worldwide $727m $74m $11m
Roche Europe $1,019m $2,396m $1,218m $1,704m $2,272m $295m $284m
Japan $140m $708m $513m $375m $852m $170m $68m
ROW $715m $507m $720m $1,136m $2,133m $1,136m $74m $85m $227m
USA $2,982m $1,247m $7,384m $407m $8,293m $909m
Sanofi Europe $153m $987m $41m $1,474m $368m $890m
ROW $307m $1,597m $1,443m $123m
USA $952m $165m $250m $8,107m $337m
UCB Europe $530m
ROW $342m
USA $1,632m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036
Expiry Year
Source: Redburn
If we include data for small molecules and vaccines, we see no year with greater than
15% of sales at risk of exposure for any company except UCB (Fig 4). We emphasise
that this chart shows the sales at risk in a given year, not the revenue decline in that
year. Save for small molecule genericisation in the US, no modality or region sees
almost immediate and total erosion.
Fig 4: Proportion of sales exposed to generics or biologics in the year of impact

35%
Percentage of sales exposed in year of expiry
30%
25%
20%
15%
10%
5%
0%
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
2022
2023
2024
2025
2026
2027
2028
AstraZeneca GlaxoSmithKline Ipsen Merck KGaA Novartis Novo Nordisk Roche Sanofi UCB
Biologic Small molecule Vaccine
Source: Redburn

The idea
Stock conclusions
Sales erosion is but one factor in an investment thesis, but it is certainly an important
one. Below we summarise how each of the European stocks features on this measure,
along with some broader context on our investment theses.
AstraZeneca (Buy, fair value 12,700p)

We expect limited exposure in any given year this decade, with significant expiries in
2031 and 2035 such as Tagrisso, Calquence and Enhertu (Fig 5). Patent expiry is
inevitable – portfolio replenishment is not – but Astra is one of the best placed
companies to restock what will be lost. R&D productivity has been exceptional in
recent years, with an increase in overall success from 4% in 2005-10 to 22% in 2016-20,
as we recently discussed (‘Investing in Pharma: Not Like the Bad Old Days…’, 1
September 2021).
A good example of this is Lynparza, Astra’s class-leading DNA damage repair

inhibitor in multiple cancers. While Lynparza is set to lose exclusivity from 2027, Astra
has already moved its replacement, AZD5305, into clinical trials, which, in preclinical
studies, has demonstrated higher potency and efficacy than first-generation PARP
inhibitors such as Lynparza. A broad base of current and pipeline growth
opportunities is essential to maintaining revenue growth over the long term, and it is
testament to the Astra portfolio that we still expect sales growth of c7% in 2025-26
despite around 10% of sales being exposed to erosion. We reiterate our Buy
recommendation and Astra continues to be our top pick.

The idea
Fig 5: AstraZeneca marketed portfolio expiry profile

Drug n ame
Onglyza/Kombiglyze 232m 87m
Bydureon 49m 230m Type group
Soliris 3,118m Biologic
Daliresp/Daxas 1m 10m Small molecule
Zoladex 751m Vaccine
AZD1222 150m
Faslodex 198m
Brilinta 1,993m
Farxiga/Qtern 329m 2,787m 1,078m
Pulmicort 1,190m
Symbicort 812m
Lynparza 1,600m 2,847m 1,087m
Bevespi 275m
Breztri (PT010) 120m 750m
Fasenra 2,600m 700m
Andexxa 140m 314m
Evrenzo 815m
FluMist 140m
Imfinzi 5,600m
Kanuma 141m 59m
Koselugo (se lumetinib) 256m
Calquence 700m 4,700m
Lokelma 1,125m
Tagrisso 6,400m 4,000m
Anifrolumab 500m
Enhertu 6,000m
Ultomiris 2,250m 2,800m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
GlaxoSmithKline (Buy, fair value 2,140p)

Few, if any, companies have received more questions about patent expiries in recent
years than GSK, the issue being the expiry of the dolutegravir patent in April 2028, a
key component of a number of the company’s HIV cocktails, including Juluca and
Dovato (Fig 6).
Fig 6: GSK marketed portfolio expiry profile

Drug n ame
Relvar/Breo 374m 416m 500m
Avamys/Veramyst 317m
Triumeq 420m 590m 250m Type group
Tivicay 522m 157m Biologic
Bexsero 115m 352m 406m Small molecule
Fluarix Tetra 603m 109m Vaccine
Menveo 335m
Anoro 363m 250m 150m
Incruse 129m 90m 160m
Nucala 333m 325m 922m
Benlysta 832m 88m 95m
Dovato 550m 763m
Juluca 517m 138m
Mosquirix 3m 50m
Zejula 150m 400m 1,000m
Trelegy 1,553m 910m
Blenrep 300m
Cabotegravir/rilpivirine 2,450m
Duvroq
Jemperli 150m 250m
Rukobia 375m 86m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn

The idea
Needless to say, this challenge and its solutions featured centrally in GSK’s June 2021
investor day (Fig 7). We agree with the company’s assertion that it can grow through
the loss of dolutegravir in 2028 over the 2026-31 period, although 2028 itself will
certainly see a revenue decline; this is beyond our explicit forecast period, but we
estimate it will be -6%.
Fig 7: Glaxo’s long-term revenue aspirations
Source: company
At first glance, another issue looms in 2028 and 2029, the patent expiry of Shingrix,
GSK’s shingles vaccine. However, we are yet to experience the launch or indeed the
development of a biosimilar vaccine due to the very high investment needed, and we
do not expect any change in this behaviour.
Unlike Astra, GSK’s ability to replenish its pipeline is not yet a settled matter in
investors’ minds. However, we see an attractive, underappreciated growth story
without reliance on pipeline success, which is not reflected in the 27% 2020 P/E
multiple discount to the sector. We reiterate our Buy recommendation and raise our
fair value from 2,110p to 2,140p to reflect changes made to the patent expiry and peak
year assumptions for cabotegravir.
Novartis (Buy, fair value CHF126)

The near-term expiry profile for Novartis is unusually fluid, due to the situation
surrounding the multiple sclerosis drug Gilenya. While the patent, which was
unexpectedly upheld, expires in June 2027, Novartis has settled with challengers to
permit earlier entry at an undisclosed date. We have assumed 2023. Aside from that,
Novartis has a number of relatively modest generic entry points, mostly small
molecule, before the Entresto (heart failure) expiries in 2026-27. The largest exclusivity
loss event in our analysis period is for Cosentyx in February 2030. There is, however,
potential upside to that date, at least in psoriasis. We have identified two method-of-
use patents that extend to October 2031 and February 2032, and while such patents

The idea
represent less robust protection, Novartis has successfully defended such claims
before, in the case of Gilenya.
Fig 8: Novartis marketed portfolio expiry profile

Drug n ame
Tasigna 1,741m
Promacta 1,008m 936m
Votrient 176m 299m
Zortress / Certican 370m
Ilaris 513m 643m
Type group
Jakavi 1,210m
Biologic
Ultibro 621m
Small molecule
Entresto 2,842m 2,827m
Vaccine
Cosentyx 6,880m
Lutathera 627m 600m
Mayzent 3,150m
Royalties 1,000m
Xiidra 1,300m 300m
Kesimpta(ofatumumab) 519m 1,000m
Kisqali 1,000m 1,200m
Piqray (BYL719) 750m 1,500m
Rydapt 425m
Tafinlar / Mekinist 1,500m 1,200m
Adakveo 1,000m
Kymriah 1,450m
Beovu ( RTH258) 2,300m
Aimovig 1,100m
Zolgensma 3,000m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
Taken in aggregate, Novartis’ marketed portfolio offers growth and decline in broadly
equal and opposite measure, upon which there is growth potential in the near term
from its late-stage pipeline, with gene therapy offering a considerable boost in the
second part of the decade and beyond, as we have previously discussed (‘Gene Genie’,
21 November 2019). We argue that neither the near-term growth potential (most
notably from cholesterol-lowering agent Leqvio) nor the contribution from gene
therapy is currently reflected in the share price and reiterate our Buy recommendation.
Roche (Buy, fair value CHF 430)

Before biosimilars legislation, generic competition was ‘something that happened to
other people’ as far as Roche was concerned. The development of the regulatory
framework on biosimilars has changed that dramatically, with Roche facing
competition on three fronts simultaneously: Herceptin, Rituxan and Avastin. Being
the first major US biosimilar entries, forecasting the trajectory of the impact proved
challenging and created a period of prolonged negative estimate momentum, which
has recently begun to abate, but not before inflicting a meaningful derating.
Thankfully, the biosimilar threat in the coming years is smaller (Fig 9). The next
potential entry is in 2024 for ex-US Kadcyla, but it is possible that this date is
somewhat more distant because there is potentially protection beyond 2030 from
secondary patents; the US date of July 2026 is the expiry of the patent for which an
extension was sought and granted.

The idea
Fig 9: Roche marketed portfolio expiry profile

Drug n ame
Esbriet 1,133m
Actemra 629m
Erivedge 39m 75m 242m Type group
Kadcyla 1,466m 1,098m Biologic
Alecensa 375m 550m 450m 850m Small molecule
Gazyva 1,132m 330m Vaccine
Perjeta 3,822m 2,329m
Cotellic 139m 46m
Tecentriq 1,000m 1,500m 750m 4,000m
Ocrevus 8,500m 1,000m
Rozlytrek 600m
Hemlibra 1,037m 1,073m 3,300m
Activase 65m
Pulmozyme 871m
Venclexta 1,051m
Xofluza 1,850m
Polivy 485m 800m
Enspryng (satralizumab) 359m 260m
Risdiplam 3,650m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
2025 is the reasonable first entry for Perjeta biosimilars in the US, based on the
expiration of the extended patent, but again there is potential IP until 2038. The
biggest potential erosion is in October 2028, when Ocrevus’ principal patent expires.
Set against these undoubted challenges, Roche benefits from a full pipeline and a
multi-decade track record of delivery. As the current wave of biosimilar erosion
diminishes, we forecast an improvement in revenue growth, from c2% in 2022 to c5%
for 2023-27. That trajectory could receive a fillip in 1H22 if gantenerumab in
Alzheimer’s is successful. We remain extremely sceptical of the amyloid hypothesis
upon which this and other drugs are based, despite Biogen’s controversial approval of
related drug Aduhelm earlier this year. Were it to be approved, around 1% would be
added to the 2023+ growth rate and CHF10/share to our fair value. We reiterate our
Buy recommendation and CHF430 fair value.
UCB (Buy, fair value €136)

No company in our universe faces the degree of biosimilar and generic competition
that will befall UCB, but not only is this well understood, it has guided the company’s
strategy for many years, ensuring the pipeline has more than sufficient replacement
power. The two key expiries are for small molecule Vimpat (epilepsy) and antibody
fragment Cimzia (inflammation) in 2022 and 2024 respectively. Beyond that, there are
no comparable expiries until Evenity (osteoporosis) in 2031.

The idea
Fig 10: UCB marketed portfolio expiry profile

Drug n ame
Neupro 266m 70m
1,412m Type group
Vimpat Biologic
Cimzia 2,039m
Small molecule
Briviact 582m 100m
Vaccine
Nayzilam 160m
Evenity 2,000m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
At the other end of the product cycle, Bimzelx (psoriasis) has recently been approved
in Europe and US approval is expected on 15 October. As we have previously
discussed (‘12-Year Itch’, 6 January 2021), Bimzelx’s best-in-class efficacy, even when
tempered by UCB’s lower marketing heft than its larger peers (AbbVie, Novartis and
Johnson & Johnson), will make a very meaningful commercial impact relative to the
company’s size. We argue that ‘commercialisation discount’ applied by the market is
over-influenced by the experience of Cimzia, a late-following undifferentiated product
in a crowded market, in contrast to the efficacy profile in this case. We reiterate our
Buy recommendation and fair value of €136.
Merck KGaA (Buy, fair value €184)

Given the conglomerate structure of Merck KGaA, drug exclusivity constitutes a less
pressing issue, as the majority of the business (Life Sciences and Electronics) falls
outside its scope. Nevertheless, we include the analysis for completeness. The first
major biosimilar threat comes in 2025 for Erbitux, but development in this area has
been muted; Merck only has ex-US rights. After that comes Mavenclad, where there is
potential for extension beyond October 2026 in the US and August 2027 in Europe.
Fig 11: Merck KGaA marketed portfolio expiry profile

Drug n ame
Erbitux 568m
Type group
Mavenclad 149m 760m 646m
Biologic
Gonal-f 703m
Small molecule
Rebif 84m
Vaccine
Bavencio 1,515m 1,900m
Tepotinib 1,175m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
Novo Nordisk (Neutral, fair value DKK510)

The expiry profile of Novo looks benign for the remainder of this decade. Although
essentially a portfolio consisting entirely of biologic drugs, reasons of regulatory
history mean that is not quite the whole story. Insulins were originally approved via
the small molecule regulatory pathway, in the absence of any other route, but were
moved to biologic status a few years ago. GLP-1 analogues, such as Victoza and
Ozempic, remain in the small molecule camp so are deprived 12-year data exclusivity
and the challenges of interchangeability that are a contention for biosimilars.

The idea
Fig 12: Novo Nordisk marketed portfolio expiry profile

Drug n ame
Victoza 1,520m 3,699m 6,460m
3,185m 4,498m 250m Type group
Saxenda Biologic
Ryzodeg 4,000m
Small molecule
Tresiba 1,295m 7,700m 14,000m
Vaccine
Xultophy 16m 5,600m 5,000m
FiAsp 500m 5,800m
Ozempic 16,158m 8,000m 40,000m
NovoEight & analogues 70m
Rybelsus 3,337m 29,000m
Somapacitan 150m 150m 175m
Wegovy (sem aglutide) 33,999m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
The only meaningful near-term expiry relates to Victoza and Saxenda. Teva settled
Victoza legislation so it may enter the US market in 2023, but the outstanding success
of Ozempic has rendered this a fairly pyrrhic victory, given the residual market size.
Semaglutide, the active ingredient in Ozempic, Wegovy and Rybelsus, has
composition-of-matter patent protection until December 2031. With combined
forecast exposure of over DKK100bn, that represents an enormous challenge for Novo
in a decade, but also for any putative generic challenger, given the investment required
to produce the active ingredient. We remain Neutral on Novo, impressed by its quality
but less enamoured of its current valuation. Our fair value remains DKK510.
Ipsen (Neutral, fair value €99)

The principle point for debate over recent years on Ipsen’s expiry profile has been with
respect to Somatuline, both directly and from Novartis’ genericised Sandostatin LAR.
There are no unexpired US or European patents on the product, but the challenges of
manufacturing have so far resulted in limited European country launches (notably
Germany) and nothing is expected in the US in 2021.
Fig 13: Ipsen marketed portfolio expiry profile

Drug n ame
Somatuline 1,100m
560m Type group
Dysport Biologic
Increlex 25m
Small molecule
Cabometyx 680m
Vaccine
Onivyde 200m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
After Somatuline, we see the risk to Dysport, Ipsen’s botulinum toxin, as modest,
given the nature of the product, leaving the 2029 Cabometyx expiry as the next
significant event; Ipsen has rights outside North America and Japan. The investment
thesis for Ipsen is based on the company’s ability to traverse the Somatuline loss, and
we view progress under CEO David Loew as generally positive. The market, however,
viewed the delay in August 2021 to pipeline asset palovarotene (fibrodysplasia
ossificans progressiva) very negatively. Despite our NPV valuation of €2.2/share, the

The idea
stock fell around €12, with modest subsequent recovery. Absent newsflow and against
this backdrop, we maintain a Neutral recommendation.
Sanofi (Neutral, fair value €93)

The number of products within the Sanofi portfolio facing biosimilar or generic
competition in the next eight years is high by the standards of its peers, but the total
sales impact is very modest. Dupixent in 2029 and 2031 is the only major issue with
which the company has to contend. While we believe some vaccines will lose
protection towards the end of this decade, there is no market for biosimilar vaccines
today and we see no change in that position.
Fig 14: Sanofi marketed portfolio expiry profile

Drug n ame
Apidra 125m 21m 250m
Toujeo 203m 400m 525m
Type group
Eloctate 193m 174m Biologic
Jevtana 349m 38m Small molecule
Aldurazyme 109m Vaccine
Mozobil 40m 61m 130m
Aubagio 136m 21m 56m
Cerdelga 192m 220m
Kevzara 216m 500m
Praluent 155m 700m 475m
Adult Booster Vaccines 880m
Dupixent 2,500m 6,100m
Influenza Vaccines 2,400m
Meningitis/Pneumonia 920m
Polio / Pertussis / Hib 2,750m
Travel And Other Endemics 700m
Alprolix 364m 200m
Cablivi 300m 274m
Fabrazyme 275m
Libtayo 450m
Myozyme 779m 250m
Thymoglobulin 326m
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037
Expiry Year
Source: Redburn
Considering erosion and competition alone, Sanofi is very well placed. However, our
Neutral recommendation is as a result of the other part of the revenue equation:
growth. Sanofi’s ability to generate organic revenue expansion through R&D was
underwhelming for much of the past 15 years. Recent efforts under CEO Paul Hudson
and head of R&D John Reed have sought to address this, but so far we do not see
sufficient evidence of a concerted improvement. The ample balance sheet has been
deployed on a number of potentially interesting acquisitions, but the central question
about Sanofi’s intrinsic ability to discover and develop drugs itself is to be answered
adequately. Our fair value remains €93 and we maintain a Neutral recommendation.
Fig 15 provides summary valuation details for all of the companies.

The idea
Fig 15: European pharma summary multiples and valuations

Mcap ---- P/E ---- EV/EBITDA --- 2020-23 growth -- -- FCF yield - Div yld
Company Price FV ($m) 2022 2023 2022 2023 Sales EBIT EPS 2021 2022 2021
AstraZeneca (Buy) GBp 8,855 12,700 187,753 15.7x 13.2x 12.3x 10.5x +11% +19% +19% 0.0% 3.2% 2.3%
GlaxoSmithKline (Buy) GBp 1,401 2,140 96,486 12.0x 10.8x 9.0x 8.3x +6% +10% +11% 3.7% 5.1% 5.7%
Novartis (Buy) CHF 76.5 126 202,208 11.7x 11.4x 11.4x 11.1x +4% +6% +7% 5.8% 6.4% 3.7%
Novo Nordisk (Neutral) DKK 644 510 232,034 27.5x 25.0x 19.5x 18.0x +9% +10% +11% 2.7% 3.2% 1.6%
Roche (Buy) CHF 357 430 340,505 16.4x 15.4x 11.9x 11.2x +5% +7% +7% 4.7% 5.2% 2.7%
Sanofi (Neutral) EUR 83.5 93 122,486 12.3x 12.2x 8.5x 8.4x +3% +2% +2% 6.6% 7.0% 3.9%
Ipsen (Neutral) EUR 86.0 99 8,368 10.4x 10.0x 7.0x 6.7x +1% +2% +2% 6.8% 8.3% 1.2%
Merck KGaA (Buy) EUR 191.5 184 96,632 21.6x 19.6x 14.9x 13.7x +7% +8% +9% 3.1% 3.5% 1.1%
UCB (Buy) EUR 97.2 136 21,947 16.6x 14.9x 13.0x 12.0x +4% +7% +9% 6.0% 6.3% 1.4%
Sector 16.7x 15.4x 12.6x 11.7x +5% +8% +9% 3.8% 4.8% 2.8%
Source: Redburn

01/
01/ Patent and exclusivity data
Patent and exclusivity data

Here we list the expiry and exclusivity details for biologic drugs
approved in the US since 2000 and potentially related patents that
may extend protection beyond such time. We also include consensus
sales forecasts for 2021-30 and the description and approved
indications from the latest FDA label.

How we assembled the data

Having said there is no complete source of biologic drug patents, there is partial
information 1 for some drugs, maintained by the US Patent Office. Drug companies are
entitled to time credits for the period taken to develop and approve novel drugs, up to
five years with a cap of 14 years of market exclusivity. The problem with this is a lack
of agency urgency. Since the application for patent term extensions must be made
within 60 days of commercial launch, the Patent Office has many years to opine on the
validity of the application, and it regularly takes its time. In some cases, a decade may
elapse, which means most drug launched in the past five years do not have a granted
application. If they do, we use this as a starting point, on the basis that the patent
chosen for extension must, in most cases, be the critical patent for the drug.
Failing this, our second approach is to search the Patent Office records. Although a
decision on the application may not have been made, the application itself is publicly
available on the Public Patent Application Information Retrieval 2 website (PAIR). This
records every aspect of a patent’s life from application through to expiry, with all the
relevant documentation. However, this website suffers from a fatal limitation – to find
the extension application and thus the key patent, we need the patent number itself.
To get around this problem, we used the Patent Examination Data System 3 to
download the detailed records of all life science patents from 2000 (approximately
784,000). From this, we could extract the details of all patents for which an extension
application was made and, using PAIR, manually download those applications and
extract the contents to give the patent details and connected drug names.
Finally, for some drugs, there is no extension application. This is generally for two
reasons: either the drug is not truly novel and therefore ineligible for extension or it
was developed particularly quickly, such that the unextended patent already provides
14 years of protection. In these cases, we performed manual searches to identify the
key patent. In the main section, the source for each key patent is indicated (Fig 16).
1
https://www.uspto.gov/patents/laws/patent-term-extension/patent-terms-extended-under-35-usc-156
2
https://portal.uspto.gov/pair/PublicPair
3
https://ped.uspto.gov/peds/#!/

Fig 16: Key patent information for Astra’s Fasenra from Chapter 1
Source: Redburn
Unlike most small molecules, which have relatively small sets of protecting patents,
biologics can have dozens, so the key patent is only the starting point. A full list of
patents is probably only achievable by the owners, since we do not know all of the
intricacies of a biologic’s development and manufacture. However, by looking at all of
the owner’s other patents that cite this key patent, we can achieve a fairly
comprehensive list; for example, we discovered around 90% of the relevant patents (as
disclosed in litigation) for AbbVie’s Humira using this approach. We used the lens.org
website 4 to obtain these citations and Google Patents to find anticipated expiry dates.
We note that these citing patents are potentially relevant to the drug in question. We
have manually curated the lists to remove the obviously irrelevant, but a detailed
examination of the thousands listed here was not possible.
We have also included a description and most up-to-date approved indications for
each drug from the latest FDA label. This was done for all biologics (BLA) approvals
since 2000 using the Drugs@FDA database 5, which means that vaccines and some
blood products are excluded. However, with no market for generic or biosimilar
vaccines now or expected in the future, this has limited impact. We have also excluded
products for which there is already established biosimilar competition, such as Roche’s
Herceptin and Avastin.
Finally, where available, we include Visible Alpha global consensus drug estimates for
2021-30, their 95% confidence intervals and their interquartile range, using the
methodology we recently outlined (‘Feeling Confident?’, 23 July 2021). For drugs with
shared global marketing rights, such as Sanofi and Regeneron’s Dupixent, the sales
depicted are those for the US booked by the company responsible for that territory.
Where the key patent expiry or data exclusivity falls within this date range, we have
indicated them with yellow and grey lines respectively.
4
Jefferson, O. A., Koellhofer, D., Warren, B., and Jefferson, R. (2019). The Lens MetaRecord and LensID: An open identifier system for
aggregated metadata and versioning of knowledge artefacts. (https://doi.org/10.31229/osf.io/t56yh).
5
https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-data-files

AbbVie
Creon
2,000 30
1,800
25
1,600
1,400
20
1,200
1,000 15
800
10
600 11 11 11 11 11
400
7 7 7 5
200 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Creon Median
| Key patent expiry 07/02/2030 | BLA exclusivity 30/04/2021
Source: Redburn, Visible Alpha
Description
Creon is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase
contains multiple enzyme classes, including porcine-derived lipases, proteases, and amylases.
Indications
Creon is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy,
or other conditions.
Approval and Data Exclusivity

Application number: BLA20725
Approval date: 30/4/2009
12-year exclusivity estimated expiry: 30/4/2021
Key Patent
Number: 9,198,871
Source of patent: Redburn patent search
Original expiry: 07/02/2030
Extended expiry date: n/a
Patents citing, and expiring after, the key patent
There are no patents citing the key patent.

Humira
25,000 30
25
20,000
20
15,000
15
10,000
12 12 12 10
11 11
5,000 8
7 5
6
5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Humira Median
|Key patent expiry 31/12/2016 | BLA exclusivity 31/12/2014
Description
Adalimumab is a tumor necrosis factor blocker. Adalimumab is a recombinant human IgG1 monoclonal antibody created using phage
display technology resulting in an antibody with human derived heavy and light chain variable regions and human IgG1:k constant
regions. Adalimumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary (CHO)) expression
system and is purified by a process that includes specific viral inactivation and removal steps. It consists of 1330 amino acids and has a
molecular weight of approximately 148 kilodaltons. Note that patent litigation has been settled. Amgen may launch a biosimilar in
the US on 31/1/2023, Sandoz on 30/9/2023 and Pfizer on 20/11/2023
Indications
Humira is a tumor necrosis factor (TNF) blocker indicated for:
Rheumatoid Arthritis (RA): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural
damage, and improving physical function in adult patients with moderately to severely active RA.
Juvenile Idiopathic Arthritis (JIA) : reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years
of age and older.
Psoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical
function in adult patients with active PsA.
Ankylosing Spondylitis (AS) : reducing signs and symptoms in adult patients with active AS.
Crohn's Disease (CD) : treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and
older.
Ulcerative Colitis (UC) : treatment of moderately to severely active ulcerative colitis in adults and pediatric patients 5 years of age
and older. Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF
blockers.
Plaque Psoriasis (Ps): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic
therapy or phototherapy, and when other systemic therapies are medically less appropriate.
Hidradenitis Suppurativa (HS): treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
Uveitis (UV): treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and
older.

Key Patent
Number: 6,090,382
Source of patent: granted patent term extension request
Extended expiry date: 31/12/2016

Number, expiry and title
9,550,826 expires 14/11/2034 - Glycoengineered binding protein compositions
9,499,614 expires 13/3/2034 - Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using mono-

saccharides and oligosaccharides

9,085,618 expires 12/11/2033 - Low acidic species compositions and methods for producing and using the same
9,181,337 expires 12/11/2033 - Modulated lysine variant species compositions and methods for producing and using the same
9,499,616 expires 12/11/2033 - Modulated lysine variant species compositions and methods for producing and using the same
9,334,319 expires 12/10/2033 - Low acidic species compositions
9,957,318 expires 22/7/2033 - Protein purification methods to reduce acidic species
9,150,645 expires 13/5/2033 - Cell culture methods to reduce acidic species
9,181,572 expires 14/3/2033 - Methods to modulate lysine variant distribution
9,290,568 expires 14/3/2033 - Methods to control protein heterogeneity
9,346,879 expires 14/3/2033 - Protein purification methods to reduce acidic species
9,708,400 expires 14/3/2033 - Methods to modulate lysine variant distribution
9,062,106 expires 26/4/2032 - Methods for controlling the galactosylation profile of recombinantly-expressed proteins
9,624,295 expires 31/3/2031 - Uses and compositions for treatment of psoriatic arthritis
8,999,337 expires 6/2/2031 - Methods for treating juvenile idiopathic arthritis by inhibition of TNFα
8,420,081 expires 13/1/2030 - Antibody formulations and methods of making same
9,085,619 expires 28/11/2028 - Anti-TNF antibody formulations
9,669,093 expires 10/6/2028 - Methods for treating juvenile idiopathic arthritis
8,889,136 expires 9/10/2027 - Multiple-variable dose regimen for treating TNFα-related disorders
8,663,945 expires 13/9/2027 - Methods of producing anti-TNF-alpha antibodies in mammalian cell culture
8,911,964 expires 13/9/2027 - Fed-batch method of making human anti-TNF-alpha antibody
9,090,867 expires 13/9/2027 - Fed-batch method of making anti-TNF-alpha antibody
9,234,032 expires 13/9/2027 - Fed-batch methods for producing adalimumab
9,284,371 expires 13/9/2027 - Methods of producing adalimumab
8,715,664 expires 24/7/2027 - Use of human TNFα antibodies for treatment of erosive polyarthritis
8,926,975 expires 8/6/2027 - Method of treating ankylosing spondylitis
8,231,876 expires 4/4/2027 - Purified antibody composition
9,061,005 expires 22/11/2026 - Multiple-variable dose regimen for treating idiopathic inflammatory bowel disease
9,187,559 expires 11/4/2025 - Multiple-variable dose regimen for treating idiopathic inflammatory bowel disease
9,512,216 expires 11/4/2025 - Use of TNFα inhibitor
8,906,373 expires 18/7/2023 - Use of TNF-alpha inhibitor for treatment of psoriasis
9,067,992 expires 18/7/2023 - Use of TNFα inhibitor for treatment of psoriatic arthritis
8,911,737 expires 5/6/2022 - Methods of administering anti-TNFα antibodies


Skyrizi
14,000 30
12,000 25
10,000
20
8,000
15
6,000
12 12 12 12 10
4,000 11
8
2,000 7 7 5
6 6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Skyrizi Median
Description
Risankizumab-rzaa, an interleukin-23 antagonist, is a humanized immunoglobulin G1 (IgG1) monoclonal antibody. Risankizum-
ab-rzaa is produced by recombinant DNA technology in Chinese hamster ovary cells and has an approximate molecular weight of 149
kDa.
Indications
Skyrizi is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or
phototherapy.

Key Patent
Number: 8,778,346
Source of patent: pending patent term extension request

10,793,629 expires 11/1/2036 - Compound targeting IL-23A and TNF-alpha and uses thereof
10,507,241 expires 23/7/2035 - Biomarkers useful in the treatment of IL-23A related diseases

ADC Therapuetics
Zynlonta
1,200 30
1,000 25
800 20
600 15
400 10
200 5
5 5
4 4 4 4 3 3 4 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts ADCT-402 Median
Description
Loncastuximab tesirine-lpyl is a CD19-directed antibody and alkylating agent conjugate, consisting of a humanized IgG1κ monoclo-
nal antibody conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxic alkylating agent, through a protease-cleavable
valine-alanine linker. SG3199 attached to the linker is designated as SG3249, also known as tesirine. Loncastuximab tesirine-lpyl has
an approximate molecular weight of 151 kDa. An average of 2.3 molecules of SG3249 are attached to each antibody molecule. Loncas-
tuximab tesirine-lpyl is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced
by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.
Indications
Zynlonta is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of
systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lympho-
ma, and high-grade B-cell lymphoma. This indication is approved under accelerated approval based on overall response rate

Key Patent
Number: 10,780,181

Amgen
Aimovig
1,000 30
900
25
800
700
20
600
500 15
15 15 15
400 14 14
13
10
300 11
10 10
200
7 5
100
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Aimovig Median
Description
Erenumab-aooe is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to the calcitonin gene-re-
lated peptide receptor. Erenumab-aooe is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is
composed of 2 heavy chains, each containing 456 amino acids, and 2 light chains of the λ subclass, each containing 216 amino acids,
with an approximate molecular weight of 150 kDa.
Indications
Aimovig is indicated for the preventive treatment of migraine in adults.

Key Patent
Number: 9,102,731

Aranesp
1,600 30
1,400
25
1,200
20
1,000
800 15
16 16 16 16
15
600 13 13
10
11
400 10 10
5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Aranesp Median
Description
Darbepoetin alfa is an erythropoiesis-stimulating protein that is produced in Chinese hamster ovary (CHO) cells by recombinant
DNA technology. Darbepoetin alfa is a 165-amino acid protein that differs from recombinant human erythropoietin in containing 5
N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3 chains. The 2 additional N-glycosylation sites
result from amino acid substitutions in the erythropoietin peptide backbone. The approximate molecular weight of darbepoetin alfa is
37,000 daltons.
Indications
Aranesp is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia due to:
Chronic Kidney Disease (CKD) in patients on dialysis and patients not on dialysis.
The effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of
planned chemotherapy

Key Patent
Number: 5,955,422

10,765,801 expires 15/2/2037 - Drug delivery device with proximity sensor
9,320,797 expires 19/11/2029 - Pharmaceutical formulations

Blincyto
1,000 30
900
25
800
700
20
600
500 15
16 16 16 16
15
400
13 13
10
300 11
10 10
200
5
100
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Blinatumomab Median
Description
Blinatumomab is a bispecific CD19-directed CD3 T-cell engager. Blinatumomab is produced in Chinese hamster ovary cells. It con-
sists of 504 amino acids and has a molecular weight of approximately 54 kilodaltons.
Indications
Blincyto is a bispecific CD19-directed CD3 T-cell engager indicated for the treatment of adults and children with:
CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual
disease (MRD) greater than or equal to 0.1%. This indication is approved under accelerated approval based on MRD response rate and
hematological relapse-free survival.
Relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL).

Key Patent
Number: 7,112,324

Evenity
1,400 30
1,200 25
1,000
20
800
15
600
14 14 14 14
13
10
400 11 11
9 9 9
200 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Evenity Median
Description
Romosozumab-aqqg is a humanized monoclonal antibody (IgG2) produced in a mammalian cell line (Chinese Hamster Ovary) by
recombinant DNA technology that binds to and inhibits sclerostin. Romosozumab-aqqg has an approximate molecular weight of 149
kDa.
Indications
Evenity is a sclerostin inhibitor indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined
as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available
osteoporosis therapy.

Key Patent
Number: 7,592,429

10,233,237 expires 14/6/2036 - Heterodimeric immunoglobulins
9,925,260 expires 5/10/2033 - Treatment for bone diseases
9,657,090 expires 11/12/2032 - Method of treating alveolar bone loss through the use of anti-sclerostin antibodies
9,145,457 expires 14/8/2032 - Sclerostin antibody crystals and formulations thereof
10,538,584 expires 2/8/2032 - Methods for treating bone gap defects
9,920,114 expires 23/3/2032 - Antibody formulations
10,064,946 expires 11/5/2031 - High concentration antibody formulations

Neulasta
2,500 30
25
2,000
20
1,500
15
16 16 16 16
15
1,000
13
12 10
11
10 10
500
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Neulasta Median
Description
Pegfilgrastim is a covalent conjugate of recombinant methionyl human G-CSF (filgrastim) and monomethoxypolyethylene glycol.
Filgrastim is a water-soluble 175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kD). Filgrastim is
obtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmid containing the human
G-CSF gene. To produce pegfilgrastim, a 20 kD monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal
methionyl residue of filgrastim. The average molecular weight of pegfilgrastim is approximately 39 kD.
Indications
Neulasta is a leukocyte growth factor indicated to Decrease the incidence of infection, as manifested by febrile neutropenia, in patients
with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of
febrile neutropenia.
Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation
Syndrome).

Key Patent
Number: 5,824,784

10,166,189 expires 11/12/2027 - Lyophilized therapeutic peptibody formulations
10,160,958 expires 11/4/2026 - Variant forms of urate oxidase and use thereof
8,143,380 expires 17/12/2025 - Therapeutic peptides
7,700,722 expires 12/5/2025 - Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing
9,145,450 expires 25/7/2023 - Thrombopoietic compounds
7,927,589 expires 14/12/2020 - PEG-urate oxidase conjugates and use thereof
7,927,852 expires 27/9/2020 - Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates
6,586,398 expires 7/4/2020 - Chemically modified novel erythropoietin stimulating protein compositions and methods
7,262,166 expires 7/4/2020 - Chemically modified novel erythropoietin stimulating protein compositions and methods
8,921,064 expires 29/11/2019 - Method for purifying urate oxidase tetramers and octamers


7,090,835 expires 18/8/2016 - N-terminally chemically modified protein compositions and methods
Nplate
1,400 30
1,200 25
1,000
20
800
15
16 16 16 16
600 15
13 13
10
400 11
10 10
200 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Nplate Median
Description
Romiplostim is a thrombopoietin receptor agonist (TPO-RA). Romiplostim, a member of the TPO mimetic class, is an Fc-peptide
fusion protein (peptibody). The peptibody molecule contains two identical single-chain subunits, each consisting of human immuno-
globulin IgG1 Fc domain, covalently linked at the C-terminus to a peptide containing two thrombopoietin receptor-binding domains.
Romiplostim has no amino acid sequence homology to endogenous TPO. Romiplostim is produced by recombinant DNA technology
in Escherichia coli (E . coli) .
Indications
Nplate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in:
Adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or
splenectomy.
Pediatric patients 1 year of age and older with ITP for at least 6 months who have had an insufficient response to corticosteroids,
immunoglobulins, or splenectomy.
Nplate is indicated to increase survival in adults and in pediatric patients (including term neonates) acutely exposed to myelosuppres-
sive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [HS-ARS]).

Key Patent
Number: 6,835,809

10,106,612 expires 25/6/2033 - Method for selection and production of tailor-made highly selective and multi-specific targeting enti-
ties containing at least two different binding entities and uses thereof


Prolia
5,000 30
4,500
25
4,000
3,500
20
3,000
2,500 15
16 16
15 15
2,000 14
12 12 10
1,500
10 10 10
1,000
5
500
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Prolia Median
Description
Prolia (denosumab) is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of
nuclear factor κ-B ligand). Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered
mammalian (Chinese hamster ovary) cells.
Indications
Prolia is a RANK ligand (RANKL) inhibitor indicated for:
Treatment of postmenopausal women with osteoporosis at high risk for fracture
Treatment to increase bone mass in men with osteoporosis at high risk for fracture
Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate
cancer
Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Key Patent
Number: 6,740,522

8,058,418 expires 11/11/2023 - Polynucleotides encoding heavy and light chains of antibodies to OPGL
8,455,629 expires 24/4/2023 - Human anti-OPGL neutralizing antibodies as selective OPGL pathway inhibitors

Repatha
4,000 30
3,500
25
3,000
20
2,500
2,000 15
16 16 16
15 15
1,500 13 13
10
11
1,000 10 10
5
500
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Repatha Median
Description
Evolocumab is a human monoclonal immunoglobulin G2 (IgG2) directed against human proprotein convertase subtilisin kexin type 9
(PCSK9). Evolocumab has an approximate molecular weight (MW) of 144 kDa and is produced in genetically engineered mammalian
(Chinese hamster ovary) cells.
Indications
Repatha is indicated:
In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization
As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults
with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C
As an adjunct to other LDL-C-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH), to reduce
LDL-C

Key Patent
Number: 8,030,457

10,772,956 expires 19/4/2037 - Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia
by administering alirocumab
10,611,850 expires 31/1/2036 - Crystalline antibody formulations
10,850,037 expires 4/5/2035 - Injector and method of assembly
10,314,976 expires 9/4/2034 - Method of assembling and filling a drug delivery device
10,537,681 expires 30/1/2033 - Injector and method of assembly
9,561,155 expires 23/6/2032 - Method of reducing cholesterol levels using a human anti-PCSK9 antibody

Vectibix
35,000 30
30,000 25
25,000
20
20,000
15
15,000
10
10,000
5,000 7 5
6 6 6 6 6
5 5 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Vectibix Median
Description
Panitumumab is an epidermal growth factor receptor (EGFR) antagonist for intravenous use. Panitumumab is a human IgG2κ mon-
oclonal antibody with an approximate molecular weight of 147 kDa that is produced in genetically engineered mammalian (Chinese
hamster ovary) cells.
Indications
Vectibix is an epidermal growth factor receptor (EGFR) antagonist indicated for the treatment of wild-type RAS (defined as wild-type
in both KRAS and NRAS as determined by an FDA-approved test for this use ) metastatic colorectal cancer (mCRC):
In combination with FOLFOX for first-line treatment.
As monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing
chemotherapy.

Key Patent
Number: 6,235,883

10,845,364 expires 10/12/2035 - Assays for detecting T cell immune subsets and methods of use thereof
10,167,492 expires 1/12/2035 - Process for manipulating the level of glycan content of a glycoprotein
10,106,829 expires 11/12/2034 - Overexpression of N-glycosylation pathway regulators to modulate glycosylation of recombinant
proteins
proteins
proteins
10,907,186 expires 11/12/2034 - Overexpression of n-glycosylation pathway regulators to modulate glycosylation of recombinant
proteins
10,513,723 expires 9/12/2034 - Decreasing ornithine production to decrease high mannose glycoform content of recombinant proteins

10,184,143 expires 12/7/2034 - Methods for increasing mannose content of recombinant proteins
8,628,773 expires 6/4/2032 - Antigen binding proteins
10,280,227 expires 10/9/2030 - Highly concentrated pharmaceutical formulations
7,705,132 expires 1/11/2027 - Stable polypeptide formulations
8,198,508 expires 8/6/2025 - Reducing the risk of human anti-human antibodies through V gene manipulation
7,598,350 expires 21/3/2025 - Human anti-epidermal growth factor receptor antibody
7,628,986 expires 25/12/2024 - Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof
7,771,958 expires 13/2/2024 - Method for predicting response to epidermal growth factor receptor-directed therapy
Xgeva
3,000 30
2,500 25
2,000 20
1,500 15
16 16 16
15
14
13
1,000 12 10
10 10 10
500 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Xgeva Median
Description
Prolia (denosumab) is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of
nuclear factor κ-B ligand). Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered
mammalian (Chinese hamster ovary) cells.
Indications
Prolia is a RANK ligand (RANKL) inhibitor indicated for:
Treatment of postmenopausal women with osteoporosis at high risk for fracture
Treatment to increase bone mass in men with osteoporosis at high risk for fracture
Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate
cancer
Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Key Patent
Number: 6,740,522




Amryt
Myalept
Description
Myalept (metreleptin) for injection is a recombinant human leptin analog for injection that binds to and activates the leptin receptor.
Metreleptin (recombinant methionyl-human leptin) is produced in E. coli and differs from native human leptin by the addition of
a methionine residue at its amino terminus. Metreleptin is a 147-amino acid, nonglycosylated, polypeptide with one disulfide bond
between Cys-97 and Cys-147 and a molecular weight of approximately 16.15 kDa. .
Indications
Myalept is a leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in
patients with congenital or acquired generalized lipodystrophy.

Key Patent
Number: 7,183,254

10,775,386 expires 17/3/2038 - Methods of detecting anti-leptin neutralizing antibodies

Astellas
Padcev
8,000 30
7,000
25
6,000
20
5,000
4,000 15
16
15 15 15 15 15
3,000 13 13
12 12 10
2,000
5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Padcev Median
Description
Enfortumab vedotin-ejfv is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a fully human anti-Nectin-4 IgG1κ
monoclonal antibody (AGS-22C3) conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE)
via a protease-cleavable maleimidocaproyl valine-citrulline (vc) linker (SGD-1006). Conjugation takes place on cysteine residues that
comprise the interchain disulfide bonds of the antibody to yield a product with a drug-to-antibody ratio of approximately 3.8:1. The
molecular weight is approximately 152 kDa. Approximately 4 molecules of MMAE are attached to each antibody molecule. Enfortum-
ab vedotin-ejfv is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by
mammalian (Chinese hamster ovary) cells and the small molecule components are produced by chemical synthesis.
Indications
Padcev is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have
previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-contain-
ing chemotherapy, or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of
therapy.

Key Patent
Number: 8,637,642

AstraZeneca
Fasenra
4,000 30
3,500
25
3,000
20
2,500
2,000 15
1,500 13 13 13 13
12 10
11
1,000 10 10 10
8
5
500
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Fasenra Median
Description
Benralizumab is a humanized monoclonal antibody (IgG1/κ-class) selective for interleukin-5 receptor α subunit (IL-5Ra). Benrali-
zumab is produced in Chinese hamster ovary cells by recombinant DNA technology. Benralizumab has a molecular weight of approx-
imately 150 kDa.
Indications
Fasenra is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosin-
ophilic phenotype

Key Patent
Number: 7,179,464

9,441,037 expires 7/8/2034 - Methods for reducing exacerbation rates of asthma using benralizumab
9,441,046 expires 7/8/2034 - Methods for increasing forced expiratory volume in asthmatics using benralizumab
9,441,047 expires 7/8/2034 - Methods for improving asthma symptoms using benralizumab
9,815,895 expires 7/4/2029 - Methods of reducing basophil levels

Imfinzi
7,000 30
6,000 25
5,000
20
4,000
15
3,000
12 10
2,000
8 8 8 8 8 8
1,000 7 7 5
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Imfinzi Median
Description
Durvalumab is a programmed cell death ligand 1 (PD-L1) blocking antibody. Durvalumab is a human immunoglobulin G1κ (IgG1κ)
monoclonal antibody that is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture.
Indications
Imfinzi is a programmed death-ligand 1 (PD-L1) blocking antibody indicated:
for the treatment of adult patients with unresectable, Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed
following concurrent platinum-based chemotherapy and radiation therapy.
in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of adult patients with extensive-stage small
cell lung cancer (ES-SCLC).

Key Patent
Number: 9,493,565

10,421,811 expires 31/12/2037 - Compositions comprising coformulation of anti-PD-L1 and anti-CTLA-4 antibodies

Kanuma
600 30
500 25
400 20
300 15
200 10
9 9 9 9
8
100 7 5
6 6
5
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Kanuma Median
Description
Kanuma (sebelipase alfa) is a recombinant human lysosomal acid lipase (rhLAL). Lysosomal acid lipase (EC 3.1.1.13) is a lysosomal
glycoprotein enzyme that catalyzes the hydrolysis of cholesteryl esters to free cholesterol and fatty acids and the hydrolysis of triglyc-
erides to glycerol and free fatty acids. Kanuma is produced by recombinant DNA technology in the egg white of eggs laid by genet-
ically engineered chickens. Purified sebelipase alfa is a monomeric glycoprotein containing 6 N-linked glycosylation sites and has a
molecular mass of approximately 55,000 daltons. The amino acid sequence for sebelipase alfa is the same as the amino acid sequence
for human LAL.
Indications
Kanuma is indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency.

Key Patent
Number: 8,663,631

10,633,705 expires 11/10/2037 - N-acetyl-alpha-D-glucosaminidase deficiency compositions and methods
8,945,542 expires 15/2/2032 - Methods for treating lysosomal acid lipase deficiency

Soliris
5,000 30
4,500
25
4,000
3,500
20
3,000
2,500 15
2,000
10
1,500
10 10 10 10
9
1,000 8
5
6 6
500 5
2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Soliris Median
Description
Eculizumab, a complement inhibitor, is a recombinant humanized monoclonal IgG2/4κ antibody produced by murine myeloma cell
culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences
and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-
chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a
molecular weight of approximately 148 kDa. Patent litigation has been settled, permitting Amgen to launch a biosimilar in the US
on 1 March 2025.
Indications
Soliris is a complement inhibitor indicated for:
The treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis
The treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangi-
opathy
The treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive
The treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody
positive

Key Patent
Number: 6,355,245

10,544,209 expires 30/7/2037 - Methods of replicating a large scale eculizumab production cell culture
9,908,932 expires 20/2/2036 - Methods of shifting an isoelectric profile of a protein product and uses thereof
10,711,057 expires 25/12/2035 - Methods of shifting an isoelectric profile of a protein product and uses thereof
10,584,164 expires 6/3/2035 - Methods of treating atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria
with anti-C5 antibodies
9,494,601 expires 6/8/2034 - Atypical hemolytic uremic syndrome (AHUS) biomarker proteins
9,658,236 expires 6/8/2034 - Atypical hemolytic uremic syndrome (aHUS) biomarker proteins
9,447,176 expires 22/8/2032 - Methods and compositions for treating complement-associated disorders
9,388,235 expires 21/6/2032 - Methods and compositions for the treatment of antibody mediated neuropathies
9,415,102 expires 14/5/2032 - High concentration formulations of anti-C5 antibodies
9,409,980 expires 6/3/2032 - Methods for treating patients with complement-associated disorders with high concentration formula-

tions of anti-C5 antibodies

9,556,263 expires 6/3/2032 - Methods for treating atypical hemolytic uremic syndrome with high concentration formulations of
anti-C5 antibodies
9,925,262 expires 6/3/2032 - Kits comprising formulations of anti-C5 antibodies
9,011,852 expires 12/2/2032 - Anti-C5a antibodies
9,221,901 expires 29/4/2031 - Methods of treating complement-associated disorders with anti-C5a antibodies
9,309,310 expires 29/4/2031 - Nucleic acids encoding anti-C5a antibodies
9,469,690 expires 29/4/2031 - Methods of treating complement-associated disorders with anti-C5a antibodies
9,963,503 expires 29/4/2031 - Methods of producing anti-C5a antibodies
10,239,937 expires 5/11/2030 - Treatment of paroxysmal nocturnal hemoglobinuria, hemolytic anemias and disease states involving
intravascular and extravascular hemolysis
9,771,418 expires 10/11/2029 - Methods for treating complement-associated disorders
9,890,377 expires 2/11/2029 - Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly
10,472,623 expires 10/4/2029 - Antigen-binding molecule capable of binding two or more antigen molecules repeatedly
9,828,429 expires 26/9/2028 - Method of modifying isoelectric point of antibody via amino acid substitution in CDR
10,590,189 expires 8/9/2027 - Treatment of paroxysmal nocturnal hemoglobinuria patients by an inhibitor of complement
10,125,191 expires 11/5/2025 - Compositions comprising an anti-C5 antibody
7,361,339 expires 25/12/2023 - Methods for reducing morality associated with acute myocardial infarction
Strensiq
1,600 30
1,400
25
1,200
20
1,000
800 15
600
10
400 9 9 9 9 9
8
7 5
200 6
5
2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Strensiq Median
Description
Asfotase alfa is a tissue nonspecific alkaline phosphatase (TNSALP) produced by recombinant DNA technology in a Chinese hamster
ovary cell line. Asfotase alfa is a soluble glycoprotein composed of two identical polypeptide chains. Each chain contains 726 amino
acids with a theoretical mass of 161 kDa. Each chain consists of the catalytic domain of human TNSALP, the human immunoglobulin
G 1 Fc domain and a deca-aspartate peptide used as a bone targeting domain. The two polypeptide chains are covalently linked by two
disulfide bonds.

Indications
Strensiq is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).

Key Patent
Number: 7,763,712

10,898,549 expires 10/10/2037 - Methods for treating hypophosphatasia in adolescents and adults
10,449,236 expires 25/6/2036 - Treating seizure with recombinant alkaline phosphatase
10,603,361 expires 3/5/2036 - Methods of treating a subject with an alkaline phosphatase deficiency
9,988,620 expires 8/6/2034 - Methods, compositions, and kits for the treatment of matrix mineralization disorders
Ultomiris
7,000 30
6,000 25
5,000
20
4,000
15
3,000
10
2,000 10
1,000 5
5 5 5 5 5
4 2 2 2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Ultomiris Median
Description
Ravulizumab-cwvz, a complement inhibitor, is a humanized monoclonal antibody (mAb) produced in Chinese hamster ovary (CHO)
cells. Ravulizumab-cwvz consists of 2 identical 448 amino acid heavy chains and 2 identical 214 amino acid light chains and has a mo-
lecular weight of approximately 148 kDa. The constant regions of ravulizumab-cwvz include the human κ light chain constant region,
and the protein engineered "IgG2/4" heavy chain constant region. The heavy chain CH1 domain, hinge region, and the first 5 amino
acids of the CH2 domain match the human IgG2 amino acid sequence, residues 6 to 36 in the CH2 region (common to both human
IgG2 and IgG4 amino acid sequences), while the remainder of the CH2 domain and the CH3 domain match the human IgG4 amino
acid sequence. The heavy and light chain variable regions that form the human C5 binding site consist of human framework regions
grafted to murine complementarity-determining regions.
Indications
Ultomiris is indicated for:
the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).
the treatment of adults and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit
complement-mediated thrombotic microangiopathy (TMA).


Key Patent
Number: 9,663,574

Bausch and Lomb

Siliq
160 30
140
25
120
20
100
80 15
60
10
40 9 9
8 8 8
5
20
4 4 4 3 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Siliq Median
Description
Brodalumab is a human monoclonal IgG2κ antibody directed against human interleukin-17 receptor A (IL-17RA). It is expressed in
a Chinese Hamster Ovary (CHO) cell line. Brodalumab is comprised of 1312 amino acids and has an estimated molecular mass of
144,000 Daltons.
Indications
Siliq is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or
phototherapy and have failed to respond or have lost response to other systemic therapies.

Key Patent
Number: 7,939,070

10,808,033 expires 4/11/2032 - IL-17 receptor antibody formulation
Vitrase
Description
Vitrase (hyaluronidase injection) Ovine is a preparation of purified ovine testicular hyaluronidase, a protein enzyme. The exact chem-
ical structure of this enzyme is unknown.
Indications
Vitrase is an endoglycosidase indicated as an adjuvant:
in subcutaneous fluid administration for achieving hydration.
For increasing the dispersion and absorption of other injected drugs.

For improving resorption of radiopaque agents, in subcutaneous urography.

Key Patent
Number: 6,939,542

Biogen
Plegridy
500 30
450
25
400
350
20
300
250 17 17 17 17 15
16
200
13
12 12 10
150
10 10
100
5
50
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Plegridy Median
Description
Peginterferon beta-1a is a covalent conjugate of recombinant interferon beta-1a (approximate molecular weight [MW] 20,000 daltons)
with a single, linear methoxy poly(ethyleneglycol)-O-2-methylpropionaldehyde molecule (approximate MW 20,000 daltons). Interfer-
on beta-1a is produced as a glycosylated protein using genetically-engineered Chinese hamster ovary cells into which the human in-
terferon beta gene has been introduced. The amino acid sequence of recombinant interferon beta-1a is identical to that of the human
interferon beta counterpart. The molecular weight of peginterferon beta-1a is approximately 44,000 daltons, consistent with the mass
of the protein, the carbohydrate moieties (approximately 2,500 daltons), and the attached poly(ethylene glycol). Peginterferon beta-1a
125 mcg contains 125 mcg of interferon beta-1a plus 125 mcg of poly(ethylene glycol).
Indications
Plegridy is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relaps-
ing-remitting disease, and active secondary progressive disease, in adults.

Key Patent
Number: 7,446,173

Tysabri
3,000 30
2,500 25
2,000 20
19 19 19 19
18
1,500 15
15
14 14
1,000 12 12 10
500 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Tysabri Median
Description
Natalizumab is a recombinant humanized IgG4κ monoclonal antibody produced in murine myeloma cells. Natalizumab contains hu-
man framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. The molecular
weight of natalizumab is 149 kilodaltons.
Indications
Tysabri is indicated for treatment of:
Multiple Sclerosis (MS) as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syn-
drome, relapsing-remitting disease, and active secondary progressive disease, in adults.
Crohn's Disease (CD) Tysabri is indicated for inducing and maintaining clinical response and remission in adult patients with mod-
erately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to
tolerate, conventional CD therapies and inhibitors of TNF-a.

Key Patent
Number: 5,840,299

10,677,803 expires 27/5/2034 - Method of assessing risk of PML
9,796,780 expires 14/5/2033 - LINGO-2 antagonists for treatment of conditions involving motor neurons
9,717,453 expires 19/4/2033 - Cognitive composite parameters and uses thereof for evaluating multiple sclerosis
10,466,251 expires 20/3/2032 - Methods of treating inflammatory and autoimmune diseases with natalizumab
10,335,485 expires 15/4/2031 - Anti-VLA-4 antibodies
10,444,234 expires 11/1/2031 - Assay for JC virus antibodies
9,533,044 expires 23/2/2030 - Methods of treating inflammatory disorders using high concentration natalizumab compositions
9,745,375 expires 9/7/2029 - Compositions comprising antibodies to LINGO or fragments thereof
8,410,115 expires 15/8/2027 - Methods of treating inflammatory and autoimmune diseases with alpha-4 inhibitory compounds
8,124,350 expires 2/8/2027 - Methods and products for evaluating an immune response to a therapeutic protein

8,900,577 expires 11/5/2024 - Immunoglobulin formulation and method of preparation thereof
8,815,236 expires 9/2/2024 - Method for treating multiple sclerosis and crohn's disease
7,807,167 expires 25/2/2023 - Administration of agents for the treatment of inflammation
7,211,252 expires 18/10/2019 - Methods of treating multiple myeloma and myeloma-induced bone resorption using integrin antago-
nists
Zinbryta
Description
Daclizumab is a humanized monoclonal antibody that binds to the α subunit of the interleukin-2 receptor (IL-2Rα, CD25). Daclizum-
ab is composed of two humanized γ-1 heavy chains and two humanized κ light chains and has a molecular weight of approximately
144 kilodaltons (kDa)
Indications
Zinbryta is an interleukin-2 receptor blocking antibody indicated for the treatment of adult patients with relapsing forms of multiple
sclerosis (MS). Because of its safety profile, the use of Zinbryta should generally be reserved for patients who have had an inadequate
response to two or more drugs indicated for the treatment of MS

Key Patent
Number: 8,454,965

Biomarin
Aldurazyme
250 30
25
200
20
150
15
15 15
100 14 14 14
12 10
11 11 11 11
50
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Aldurazyme Median
Description
Aldurazyme (laronidase) is a polymorphic variant of the human enzyme a-L-iduronidase that is produced by recombinant DNA tech-
nology in a Chinese hamster ovary cell line. a-L-iduronidase (glycosaminoglycan a-L-iduronohydrolase, EC 3.2.1.76) is a lysosomal
hydrolase that catalyzes the hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparan sulfate. Laronidase is
a glycoprotein with a molecular weight of approximately 83 kD. The predicted amino acid sequence of the recombinant form, as well
as the nucleotide sequence that encodes it, are identical to a polymorphic form of human a-L-iduronidase. The recombinant protein
is comprised of 628 amino acids after cleavage of the N-terminus and contains 6 N-linked oligosaccharide modification sites. Two
oligosaccharide chains terminate in mannose-6-phosphate sugars.
Indications
Aldurazyme is indicated for adult and pediatric patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I)
and for patients with the Scheie form who have moderate to severe symptoms.

Key Patent
Number: 6,426,208

9,044,473 expires 18/2/2031 - Delivery of therapeutic compounds to the brain and other tissues

Brineura
600 30
500 25
400 20
300 15
16 16 16 16
15
13
200 12 12 12 12 10
100 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Brineura Median
Description
Cerliponase alfa is a purified human enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line. The ac-
tive substance is a recombinant human tripeptidyl peptidase-1 (rhTPP1), a lysosomal exopeptidase. The primary activity of the mature
enzyme is the cleavage of N-terminal tripeptides from a broad range of protein substrates. Cerliponase alfa contains 544 amino acids
with an average molecular mass of 59 kDa. The mature enzyme is 368 amino acids in length. There are 5 consensus N-glycosylation
sites on rhTPP1 that contain high mannose, phosphorylated high mannose and complex glycosylation structures.
Indications
Brineura is indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neu-
ronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.

Key Patent
Number: 8,029,781

Palynziq
1,400 30
1,200 25
1,000
20
800
15
16
600 15
14 14 14
12 10
400 11 11 11 11
200 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Palynziq Median
Description
Pegvaliase-pqpz is a phenylalanine-metabolizing enzyme that is composed of recombinant phenylalanine ammonia lyase (rAvPAL)
conjugated to N-hydroxysuccinimide (NHS)-methoxypolyethylene glycol (PEG). rAvPAL is manufactured in Escherichia coli bacteria
transformed with a plasmid containing the phenylalanine ammonia lyase (PAL) gene derived from Anabaena variabilis . During the
rAvPAL manufacturing process, fermentation is carried out in nutrient medium containing the antibiotic kanamycin. However, kan-
amycin is cleared in the manufacturing process and is not detectable in the final product. rAvPAL is a homotetrameric protein with
a molecular weight of 62 kD per monomer. To produce pegvaliase-pqpz, an average of nine (9) 20 kD PEG molecules are covalently
bound (or conjugated) to each monomer of rAvPAL. The total molecular weight of pegvaliase-pqpz (rAvPAL-PEG) is approximately
1000 kD.
Indications
Palynziq is indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncon-
trolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.

Key Patent
Number: 7,534,595

Vimizim
1,200 30
1,000 25
800 20
600 15
16
15 15
14 14
400 12 12 12 10
11 11
200 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Vimizim Median
Description
Vimizim is a formulation of elosulfase alfa, which is a purified human enzyme produced by recombinant DNA technology in a Chi-
nese hamster ovary cell line. Human N-acetylgalactosamine-6-sulfatase (EC 3.1.6.4) is a hydrolytic lysosomal glycosaminoglycan-spe-
cific enzyme that hydrolyzes sulfate from either galactose-6-sulfate or N-acetyl-galactosamine-6-sulfate on the non-reducing ends of
the glycosaminoglycans keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Elosulfase alfa is a soluble glycosylated dimeric protein
with two oligosaccharide chains per monomer. Each monomeric peptide chain contains 496 amino acids and has an approximate mo-
lecular mass of 55 kDa (59 kDa including the oligosaccharides). One of the oligosaccharide chains contains bis-mannose-6-phosphate
(bisM6P). bisM6P binds a receptor at the cell surface and the binding mediates cellular uptake of the protein to the lysosome.
Indications
Vimizim (elosulfase alfa) is indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).

Key Patent
Number: 8,128,925

Boehringer Ingelheim
Praxbind
Description
Idarucizumab is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct
thrombin inhibitor dabigatran. Using recombinant expression technology, idarucizumab is produced in a well characterized recombi-
nant (mammalian) CHO cell line and is purified using standard technology. Idarucizumab is composed of a light chain of 219 amino
acids and a heavy chain fragment of 225 amino acids, covalently linked together by one disulfide bond between cysteine 225 of the
heavy chain fragment and cysteine 219 of the light chain, and has an estimated molecular mass of approximately 47,766 Daltons.
Indications
Praxbind is indicated in patients treated with Pradaxa when reversal of the anticoagulant effects of dabigatran is needed:
For emergency surgery/urgent procedures In life-threatening or uncontrolled bleeding

Key Patent
Number: 8,486,398

9,499,633 expires 4/11/2034 - Dabigatran antidotes
8,821,871 expires 28/3/2032 - Anticoagulant antidotes comprising antibodies that bind dabigatran and/or related compounds and
methods of use thereof

Bristol-Myers
Empliciti
450 30
400
25
350
300 20
250
15
200
150 10
100
5
50
3 3 3 3 3 1 1 1 1 1
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Empliciti Median
Description
Elotuzumab is a humanized recombinant monoclonal antibody directed to SLAMF7, a cell surface glycoprotein. Elotuzumab consists
of the complementary determining regions (CDR) of the mouse antibody, MuLuc63, grafted onto human IgG1 heavy and κ light chain
frameworks. Elotuzumab is produced in NS0 cells by recombinant DNA technology. Elotuzumab has a theoretical mass of 148.1 kDa
for the intact antibody.
Indications
Empliciti is indicated in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple mye-
loma who have received one to three prior therapies. Empliciti is indicated in combination with pomalidomide and dexamethasone
for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a
proteasome inhibitor.

Key Patent
Number: 7,709,610

10,925,867 expires 26/7/2037 - Immunotherapeutic dosing regimens comprising pomalidomide and an anti-CS1 antibody for treating
cancer

Nulojix
350 30
300 25
250
20
200
15
150
10
100
50 5
1 1 1 1 1 1 1 1 1 1
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Nulojix Median
Description
Nulojix (belatacept), a selective T cell costimulation blocker, is a soluble fusion protein consisting of the modified extracellular do-
main of CTLA-4 fused to a portion (hinge-CH2-CH3 domains) of the Fc domain of a human immunoglobulin G1 antibody. Belata-
cept is produced by recombinant DNA technology in a mammalian cell expression system. Two amino acid substitutions (L104 to E;
A29 to Y) were made in the ligand binding region of CTLA-4. As a result of these modifications, belatacept binds CD80 and CD86
more avidly than abatacept, the parent CTLA4-Immunoglobulin (CTLA4-Ig) molecule from which it is derived. The molecular weight
of belatacept is approximately 90 kilodaltons.
Indications
Nulojix is a selective T cell costimulation blocker indicated for prophylaxis of organ rejection in adult patients receiving a kidney
transplant. Use in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids.

Key Patent
Number: 7,094,874

9,926,365 expires 9/9/2033 - Methods for reducing glycoprotein aggregation
10,059,754 expires 3/1/2031 - Mammalian cell culture processes for protein production
8,378,082 expires 6/1/2030 - Anti-CD86 antibody
8,435,952 expires 12/10/2029 - Method for retarding progression to definite rheumatoid arthritis in subjects with undifferentiated
arthritis
9,012,408 expires 17/8/2029 - Method of preventing the development of rheumatoid arthritis in subjects with undifferentiated arthritis
10,508,144 expires 17/6/2028 - Carbohydrate content of CTLA4 molecules
7,528,111 expires 8/5/2027 - Method of vaccinating subjects receiving immune modulating therapy
7,510,844 expires 22/1/2027 - CD86 and CD80 receptor competition assays


10,808,021 expires 19/12/2026 - Compositions and methods for producing a composition
Opdivo
20,000 30
18,000
25
16,000
14,000
20
12,000
10,000 15
8,000
10
6,000 11 11 11 11
10
9
4,000 8
7 5
6 6
2,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Opdivo Median
Description
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody. Nivolumab is an IgG4κ immunoglobulin that has a calculat-
ed molecular mass of 146 kDa. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line.
Indications
Opdivo is a programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of:
Melanoma
patients with unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab.
patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant
setting.
Non-Small Cell Lung Cancer (NSCLC):
adult patients with metastatic non-small cell lung cancer expressing PD-L1 (=1%) as determined by an FDA-approved test, with no
EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with ipilimumab.
adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations as first-line
treatment, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy.
patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy. Patients with EGFR or
ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving
Opdivo.
Malignant Pleural Mesothelioma:
adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with ipilimumab.
Renal Cell Carcinoma (RCC):
patients with intermediate or poor risk advanced renal cell carcinoma, as a first-line treatment in combination with ipilimumab.
patients with advanced renal cell carcinoma, as a first-line treatment in combination with cabozantinib.
patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
Classical Hodgkin Lymphoma (cHL):
adult patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplanta-
tion (HSCT) and brentuximab vedotin, or 3 or more lines of systemic therapy that includes autologous HSCT.
Squamous Cell Carcinoma of the Head and Neck (SCCHN):
patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a plati-
num-based therapy.
Urothelial Carcinoma:
patients with locally advanced or metastatic urothelial carcinoma who:
have disease progression during or following platinum-containing chemotherapy
have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Colorectal Cancer:
adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single

agent or in combination with ipilimumab.

Hepatocellular Carcinoma (HCC):
patients with hepatocellular carcinoma who have been previously treated with sorafenib, as a single agent or in combination with
ipilimumab.
Esophageal Cancer:
patients with completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease, who have received
neoadjuvant chemoradiotherapy (CRT).
patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimi-
dine- and platinum-based chemotherapy.
Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma:
patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma in combina-
tion with fluoropyrimidine- and platinum-containing chemotherapy.This indication is approved under accelerated approval based on
overall response rate and duration of response.

Key Patent
Number: 8,008,449

10,414,747 expires 2/10/2037 - Benzo[b]thiophene compounds as sting agonists
10,392,442 expires 12/4/2037 - Use of anti-PD-1 antibody in combination with anti-CD27 antibody in cancer treatment
10,512,689 expires 13/3/2037 - Compositions comprising a combination of nivolumab and ipilimumab
10,544,224 expires 25/12/2036 - Method of treating cancer using immune checkpoint inhibitor
10,174,113 expires 26/11/2036 - Treatment of PD-L1-negative melanoma using an anti-PD-1 antibody and an anti-CTLA-4 antibody
10,869,924 expires 5/11/2036 - PD-L1 antagonist combination treatments
10,800,846 expires 24/8/2036 - PD-1/PD-L1 inhibitors for the treatment of cancer
10,945,990 expires 27/6/2036 - Combination of a PD-1 antagonist and eribulin for treating cancer
10,406,251 expires 24/11/2035 - PD-L1 binding polypeptides for imaging
10,695,426 expires 25/10/2035 - Combination of a PD-1 antagonist and an ALK inhibitor for treating cancer
10,081,681 expires 30/4/2035 - Combination of anti-LAG-3 antibodies and anti-PD-1 antibodies to treat tumors
10,737,113 expires 10/4/2035 - Human antibodies to PD-1
10,570,202 expires 3/2/2035 - Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer
9,827,309 expires 15/8/2034 - Treating cancer with a combination of a PD-1 antagonist and dinaciclib
9,856,320 expires 7/5/2034 - Cancer immunotherapy by disrupting PD-1/PD-L1 signaling
9,688,721 expires 11/2/2034 - Tubulysin compounds, methods of making and use
9,212,224 expires 24/5/2033 - Antibodies that bind PD-L1 and uses thereof


9,156,850 expires 11/2/2033 - Enediyne compounds, conjugates thereof, and uses and methods therefor
10,167,337 expires 30/9/2030 - Combination immunotherapy for the treatment of cancer
9,834,605 expires 14/5/2029 - Antibodies to human programmed death receptor PD-1
8,779,105 expires 1/9/2027 - Monoclonal antibodies to programmed death 1 (PD-1)
9,492,539 expires 9/1/2027 - Monoclonal antibodies to Programmed Death 1 (PD-1)
9,492,540 expires 14/12/2026 - Methods for treating cancer using anti-PD-1 antibodies
9,358,289 expires 20/9/2026 - Methods for treating cancer using anti-PD-1 antibodies in combination with anti-CTLA-4 antibodies
9,084,776 expires 2/5/2026 - Methods for treating cancer using anti-PD-1 antibodies
Orencia
4,500 30
4,000
25
3,500
3,000 20
2,500
15
2,000
1,500 10
11
10 10 10 10
1,000 9
8
7 5
500 6 6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Orencia Median
Description
Abatacept is a selective T cell costimulation modulator. Abatacept is a soluble fusion protein that consists of the extracellular domain
of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc (hinge, CH2, and CH3 domains) portion
of human immunoglobulin G1 (IgG1). Abatacept is produced by recombinant DNA technology in a mammalian cell expression sys-
tem. The apparent molecular weight of abatacept is 92 kilodaltons.
Indications
Orencia is a selective T cell costimulation modulator indicated for the treatment of:
Adult patients with moderately to severely active rheumatoid arthritis (RA)
Patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA)
Adult patients with active psoriatic arthritis (PsA)

Key Patent
Number: 5,851,795


8,435,952 expires 12/10/2029 - Method for retarding progression to definite rheumatoid arthritis in subjects with undifferentiated
arthritis
7,528,111 expires 8/5/2027 - Method of vaccinating subjects receiving immune modulating therapy
7,510,844 expires 22/1/2027 - CD86 and CD80 receptor competition assays
10,808,021 expires 19/12/2026 - Compositions and methods for producing a composition
7,482,327 expires 6/4/2026 - Methods for treating immune disorders associated with graft transplantation with soluble CTLA4 mutant
molecules
7,671,022 expires 19/5/2025 - Methods for treating cardiovascular disease using a soluble CTLA4 molecule
7,928,074 expires 31/10/2024 - Combination therapy with co-stimulatory factors
7,307,064 expires 3/8/2024 - Methods for treating cardiovascular disease using a soluble CTLA4 molecule
7,332,303 expires 18/12/2023 - Product quality enhancement in mammalian cell culture processes for protein production
7,829,534 expires 2/6/2023 - Methods for protecting allogeneic islet transplant using soluble CTLA4 mutant molecules
7,304,033 expires 19/2/2023 - Methods for protecting allogeneic islet transplant using soluble CTLA4 mutant molecules
7,700,556 expires 20/5/2022 - Methods of treatment using CTLA4 mutant molecules
10,052,360 expires 14/2/2022 - Methods for treating dermatomyositis or polymyositis by administering a soluble CTLA4 molecule
7,094,874 expires 31/1/2022 - Soluble CTLA4 mutant molecules
9,296,808 expires 23/10/2021 - Methods for treating scleroderma by administering a soluble CTLA4 molecule
7,455,835 expires 2/7/2021 - Methods for treating immune system diseases using a soluble CTLA4 molecule
8,148,332 expires 2/7/2021 - Methods for treating a rheumatic disease using a soluble CTLA4 molecule
8,227,420 expires 2/7/2021 - Methods for treating an autoimmune disease using a soluble CTLA4 molecule and a DMARD or NSAID
8,497,247 expires 2/7/2021 - Methods for treating type I diabetes mellitus by administering a soluble CTLA4 molecule
8,703,718 expires 2/7/2021 - Methods for treating juvenile rheumatoid arthritis by administering a soluble CTLA4 molecule
8,722,632 expires 2/7/2021 - Methods for treating Sjogrens syndrome by administering a soluble CTLA4 molecule

Reblozyl
4,000 30
3,500
25
3,000
20
2,500
2,000 15
1,500
10
11 11 11 11
1,000 10
9
8
7 5
500 6 6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Reblozyl Median
Description
Luspatercept-aamt is an erythroid maturation agent. Luspatercept-aamt is a receptor fusion protein consisting of a modified extracel-
lular domain of the human activin receptor type IIB linked to a human IgG1 Fc domain with a calculated molecular mass of approxi-
mately 76 kD. Luspatercept is produced in Chinese hamster ovary cells by recombinant DNA technology.
Indications
Reblozyl is an erythroid maturation agent indicated for the treatment of:
Anemia in adult patients with β thalassemia who require regular red blood cell (RBC) transfusions
Anemia failing an erythropoiesis stimulating agent and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to
intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm
with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)

Key Patent
Number: 8,058,229

10,550,170 expires 23/11/2036 - Methods for treating vascular eye disorders with actrii antagonists
10,189,882 expires 3/12/2035 - Methods for treating myelodysplastic syndromes and sideroblastic anemias
10,829,531 expires 3/12/2035 - Methods for treating myelodysplastic syndromes and sideroblastic anemias
10,603,359 expires 29/10/2035 - Methods and compositions using GDF15 polypeptides for increasing red blood cells
10,487,144 expires 12/6/2035 - Methods for treating ulcers in a hemoglobinopathy anemia with a soluble actRIIB polypeptide
9,850,298 expires 12/6/2035 - Methods for treating ulcers in thalassemia syndrome with an ActRIIB polypeptide

Yervoy
3,000 30
2,500 25
2,000 20
1,500 15
1,000 10
10 10 10 10 10
9
8
500 7 5
6 6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Yervoy Median
Description
Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody. Ipilimumab is a recombinant IgG1κ immu-
noglobulin with an approximate molecular weight of 148 kDa. Ipilimumab is produced in mammalian (Chinese hamster ovary) cell
culture.
Indications
Yervoy is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for:
Treatment of unresectable or metastatic melanoma in adults and pediatric patients 12 years and older.
Treatment of adult patients with unresectable or metastatic melanoma, in combination with nivolumab.
Adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm
who have undergone complete resection, including total lymphadenectomy.
Treatment of patients with intermediate or poor risk advanced renal cell carcinoma, as first-line treatment in combination with
nivolumab.
Treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient
(dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, in
combination with nivolumab. This indication is approved under accelerated approval based on overall response rate and duration of
response.
Treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib, in combination with nivolum-
ab. This indication is approved under accelerated approval based on overall response rate and duration of response.
Treatment of adult patients with metastatic non-small cell lung cancer expressing PD-L1 (=1%) as determined by an FDA-approved
test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment in combination with nivolumab.
Treatment of adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations
as first-line treatment, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy.
Treatment of adult patients with unresectable malignant pleural mesothelioma, as first-line treatment in combination with nivolumab.

Key Patent
Number: 6,984,720

10,925,867 expires 26/7/2037 - Immunotherapeutic dosing regimens comprising pomalidomide and an anti-CS1 antibody for treating
cancer

9,688,721 expires 11/2/2034 - Tubulysin compounds, methods of making and use
9,156,850 expires 11/2/2033 - Enediyne compounds, conjugates thereof, and uses and methods therefor
9,320,811 expires 3/12/2029 - Combination of anti-CTLA4 antibody with diverse therapeutic regimens for the synergistic treatment of
proliferative diseases
8,475,790 expires 5/10/2029 - Combination of CD137 antibody and CTLA-4 antibody for the treatment of proliferative diseases
8,981,071 expires 7/8/2029 - Human anti-B7RP1 neutralizing antibodies
8,449,886 expires 1/8/2029 - Combination of anti-CTLA4 antibody with tubulin modulating agents for the treatment of proliferative
diseases
9,062,111 expires 3/12/2028 - CTLA-4 antibody dosage escalation regimens
7,868,140 expires 26/10/2027 - Human anti-B7RP1 neutralizing antibodies

Daiichi Sankyo
Enhertu
3,500 30
3,000 25
2,500
20
2,000
15
1,500
10
1,000
9 9 9 9 9 9
8
500 7 7 5
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Enhertu Median
Description
Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody and topoisomerase inhibitor conjugate. Fam-trastuzumab deruxte-
can-nxki is an antibody-drug conjugate (ADC) composed of three components: 1) a humanized anti-HER2 IgG1 monoclonal anti-
body (mAb), covalently linked to 2) a topoisomerase inhibitor, via 3) a tetrapeptide-based cleavable linker. Deruxtecan is composed
of a protease-cleavable maleimide tetrapeptide linker and the topoisomerase inhibitor, DXd, which is an exatecan derivative. The
antibody is produced in Chinese hamster ovary cells by recombinant DNA technology, and the topoisomerase inhibitor and linker are
produced by chemical synthesis. Approximately 8 molecules of deruxtecan are attached to each antibody molecule.
Indications
Enhertu is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of:
adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based
regimens in the metastatic setting.This indication is approved under accelerated approval based on tumor response rate and duration
of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a con-
firmatory trial.
adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have
received a prior trastuzumab-based regimen.

Key Patent
Number: 10,195,288

Dompe
Oxervate
Description
Oxervate ophthalmic solution contains cenegermin-bkbj, a recombinant form of human nerve growth factor produced in Escherichia
coli . Cenegermin-bkbj contains 118 amino acids. Cenegermin-bkbj has a relative molecular mass of 13,266 Daltons.
Indications
Oxervate (cenegermin-bkbj) ophthalmic solution 0.002% is indicated for the treatment of neurotrophic keratitis.

Key Patent
Number: 8,501,439

Eli Lilly
Cyramza
1,800 30
1,600
25
1,400
1,200 20
1,000
15
800
600 10
400
7 7 7 7 7 5
200 5 5 5
4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Cyramza Median
Description
Ramucirumab is a human VEGFR2 antagonist. It is a recombinant human IgG1 monoclonal antibody. Ramucirumab has an approxi-
mate molecular weight of 147 kDa. Ramucirumab is produced in genetically engineered mammalian NS0 cells. Cyramza (ramucirum-
ab) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution.
Indications
Cyramza is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist indicated:
as a single agent or in combination with paclitaxel, for treatment of advanced or metastatic gastric or gastro-esophageal junction ade-
nocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
in combination with erlotinib, for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor
(EGFR) exon 19 deletions or exon 21 (L858R) mutations.
in combination with docetaxel, for treatment of metastatic non-small cell lung cancer with disease progression on or after plati-
num-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving Cyramza.
in combination with FOLFIRI, for the treatment of metastatic colorectal cancer with disease progression on or after prior therapy with
bevacizumab, oxaliplatin, and a fluoropyrimidine.
as a single agent, for the treatment of hepatocellular carcinoma in patients who have an α fetoprotein of =400 ng/mL and have been
treated with sorafenib.

Key Patent
Number: 7,498,414


Emgality
3,000 30
2,500 25
2,000 20
1,500 15
1,000 10
8 8 8
500 7 7 5
6
5 5
4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Emgality Median
Description
Galcanezumab-gnlm is a humanized IgG4 monoclonal antibody specific for calcitonin-gene related peptide (CGRP) ligand. Galcane-
zumab-gnlm is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. Galcanezumab-gnlm is composed
of two identical immunoglobulin κ light chains and two identical immunoglobulin γ heavy chains and has an overall molecular weight
of approximately 147 kDa.
Indications
Emglaity is a calcitonin-gene related peptide antagonist indicated in adults for the:
preventive treatment of migraine.
treatment of episodic cluster headache.

Key Patent
Number: 9,505,838

10,392,434 expires 22/9/2037 - Treating refractory migraine
10,519,224 expires 20/3/2035 - Treating headache comprising administering an antibody to calcitonin gene-related peptide
10,556,945 expires 20/3/2035 - Antagonist antibodies directed against calcitonin gene-related peptide and methods using same

Erbitux
600 30
500 25
400 20
300 15
200 10
8
100 7 7 7 7 5
6 6
5 5
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Erbitrux Median
Description
Cetuximab is an epidermal growth factor receptor (EGFR) antagonist. It is a recombinant, human/mouse chimeric monoclonal
antibody that binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR). Cetuximab is
composed of the Fv regions of a murine anti-EGFR antibody with human IgG1 heavy and κ light chain constant regions and has an
approximate molecular weight of 152 kDa. Cetuximab is produced in mammalian (murine myeloma) cell culture.
Indications
Erbitux is an epidermal growth factor receptor (EGFR) antagonist indicated for treatment of:
Head and Neck Cancer Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation
therapy.
Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based ther-
apy with fluorouracil.
Recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.
Colorectal Cancer K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in com-
bination with FOLFIRI for first-line treatment, in combination with irinotecan in patients who are refractory to irinotecan-based
chemotherapy, as a single-agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to
irinotecan.
Erbitux is not indicated for treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.

Key Patent
Number: 6,217,866

7,598,350 expires 21/3/2025 - Human anti-epidermal growth factor receptor antibody

Humalog Kwikpen
3,000 30
2,500 25
2,000 20
1,500 15
1,000 10
8 8 8 8 8
500 5
6 6
5 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Humalog Median
Description
Insulin lispro injection is a rapid-acting human insulin analog. Insulin lispro is produced by recombinant DNA technology utilizing a
non-pathogenic laboratory strain of Escherichia coli. Insulin lispro differs from human insulin in that the amino acid proline at posi-
tion B28 is replaced by lysine and the lysine in position B29 is replaced by proline. Chemically, it is Lys(B28), Pro(B29) human insulin
analog and has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin
Indications
Humalog is a rapid acting human insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus.

Key Patent
Number: 5,514,646

10,561,806 expires 24/5/2038 - Mouthpiece cover for an inhaler
9,855,318 expires 28/4/2036 - Fusion proteins
10,159,713 expires 17/3/2036 - Treatment of type 2 diabetes mellitus patients
10,434,147 expires 11/3/2036 - Treatment type 2 diabetes mellitus patients
9,950,039 expires 10/12/2035 - Insulin glargine/lixisenatide fixed ratio formulation
10,159,644 expires 30/6/2035 - Inhalable vaccine compositions and methods
10,421,729 expires 1/4/2035 - Microcrystalline diketopiperazine compositions and methods
10,307,464 expires 27/3/2035 - Use of ultrarapid acting insulin
9,925,144 expires 18/7/2034 - Heat-stable dry powder pharmaceutical compositions and methods
9,802,012 expires 13/7/2034 - Dry powder drug delivery system and methods
10,258,664 expires 24/10/2032 - Methods and compositions for treating pain
9,987,332 expires 4/9/2032 - Pharmaceutical composition for use in the treatment of a neurodegenerative disease
9,408,893 expires 27/8/2032 - Pharmaceutical combination for use in glycemic control in diabetes type 2 patients
10,751,488 expires 24/6/2032 - Dry powder inhaler and system for drug delivery
10,130,709 expires 22/6/2032 - High capacity diketopiperazine microparticles and methods
9,993,529 expires 15/6/2032 - Stable formulations of a hyaluronan-degrading enzyme

9,821,032 expires 9/5/2032 - Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
10,625,034 expires 1/5/2032 - Blister package for pharmaceutical cartridges
9,983,108 expires 18/10/2031 - Apparatus, system and method for measuring resistance of an inhaler
9,706,944 expires 25/8/2031 - Apparatus and method for simulating inhalation efforts
9,630,930 expires 5/3/2031 - Diketopiperazine microparticles with defined specific surface areas
10,675,421 expires 26/12/2030 - Interactive apparatus and method for real-time profiling of inhalation efforts
10,028,910 expires 11/11/2030 - Pharmaceutical composition comprising a GLP-1-agonist and methionine
10,029,011 expires 11/11/2030 - Pharmaceutical composition comprising a GLP-1 agonist, an insulin and methionine
9,707,176 expires 11/11/2030 - Pharmaceutical composition comprising a GLP-1 agonist and methionine
9,981,013 expires 30/8/2030 - Use of AVE0010 for the treatment of diabetes mellitus type 2
10,172,850 expires 29/12/2029 - Substituted diketopiperazine analogs for use as drug delivery agents
10,117,909 expires 9/10/2029 - Combination of an insulin and a GLP-1 agonist
9,526,764 expires 9/10/2029 - Combination of an insulin and a GLP-1-agonist
10,342,938 expires 12/6/2029 - Dry powder drug delivery system
10,130,581 expires 22/2/2027 - Method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and
an active agent
10,143,655 expires 14/9/2026 - Method of drug formulation
9,717,689 expires 14/9/2026 - Method of drug formulation based on increasing the affinity of crystalline microparticle surfaces for
active agents
10,130,685 expires 23/8/2025 - Diketopiperazine salts for drug delivery and related methods
7,476,652 expires 23/7/2023 - Acidic insulin preparations having improved stability
9,700,690 expires 7/3/2023 - Inhalation apparatus
7,022,674 expires 28/4/2022 - Polypeptide compositions with improved stability
7,452,860 expires 22/3/2022 - Zinc-free and low-zinc insulin preparations having improved stability
7,696,162 expires 22/3/2022 - Zinc-free and low-zinc insulin preparations having improved stability
9,801,925 expires 25/1/2021 - Potentiation of glucose elimination
6,906,028 expires 4/8/2019 - Stable insulin formulations
6,531,448 expires 21/12/2018 - Insoluble compositions for controlling blood glucose
6,268,335 expires 22/10/2018 - Insoluble insulin compositions
6,551,992 expires 11/6/2018 - Stable insulin formulations
Lartruvo
Description
Olaratumab is a recombinant human IgG1 monoclonal blocking antibody that binds specifically to human platelet derived growth fac-
tor receptor α (PDGFR-a). Lartruvo has an approximate molecular weight of 154 kDa. Lartruvo is produced in genetically engineered
mammalian NS0 cells.
Indications
Lartruvo is a platelet-derived growth factor receptor α (PDGFR-a) blocking antibody indicated, in combination with doxorubicin, for
the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen
is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.


Key Patent
Number: 8,128,929
Portrazza
Description
Necitumumab is an anti-EGFR recombinant human monoclonal antibody of the IgG1κ isotype that specifically binds to the ligand
binding site of the human EGFR. Necitumumab has an approximate molecular weight of 144.8 kDa. Necitumumab is produced in
genetically engineered mammalian NS0 cells.
Indications
Portrazza is an epidermal growth factor receptor (EGFR) antagonist indicated, in combination with gemcitabine and cisplatin, for
first-line treatment of patients with metastatic squamous non-small cell lung cancer.

Key Patent
Number: 7,598,350

Taltz
4,500 30
4,000
25
3,500
3,000 20
2,500
15
2,000
1,500 10
1,000
7 7 7 7 7 5
500 6
5
4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Taltz Median
Description
Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) with neutralizing activity against
IL-17A. Ixekizumab is produced by recombinant DNA technology in a recombinant mammalian cell line and purified using standard
technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two
identical heavy chain polypeptides of 445 amino acids each, and has a molecular weight of 146,158 Daltons for the protein backbone
of the molecule.
Indications
Taltz is a humanized interleukin-17A antagonist indicated for the treatment of:
patients aged 6 years or older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
adults with active psoriatic arthritis.
adults with active ankylosing spondylitis.
adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.

Key Patent
Number: 8,110,191

Trulicity
10,000 30
9,000
25
8,000
7,000
20
6,000
5,000 15
4,000
10
3,000
2,000 8 8 8 8
7 5
6
1,000 5 5
4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Trulicity Median
Description
Dulaglutide is a human glucagon-like peptide-1 (GLP-1) receptor agonist. The molecule is a fusion protein that consists of 2 identi-
cal, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified
human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker and is produced using mammalian cell (Chinese hamster
ovary) culture. The GLP-1 analog portion of dulaglutide is 90% homologous to native human GLP-1 (7-37). Structural modifications
were introduced in the GLP-1 part of the molecule responsible for interaction with the enzyme dipeptidyl-peptidase-IV (DPP-4).
Additional modifications were made in an area with a potential T-cell epitope and in the areas of the IgG4 Fc part of the molecule
responsible for binding the high-affinity Fc receptors and half-antibody formation. The overall molecular weight of dulaglutide is
approximately 63 kilodaltons.
Indications
Trulicity is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. to reduce
the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults
with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.

Key Patent
Number: 7,452,966

9,764,004 expires 14/10/2036 - Glucagon receptor agonists
9,884,093 expires 14/10/2036 - Glucagon receptor agonists
9,855,318 expires 28/4/2036 - Fusion proteins
8,557,769 expires 30/7/2028 - Co-administration of FGF-21 and GLP-1 to treat diabetes and lower blood glucose

Elusys Therapeutics
Anthim
Description
Obiltoxaximab is a chimeric IgG1κ monoclonal antibody (mAb) that binds the PA component of B. anthracis toxin. It has an approxi-
mate molecular weight of 148 kDa.
Indications
Anthim is a monoclonal antibody directed against the protective antigen of Bacillus anthracis. It is indicated in adult and pediatric
patients for treatment of inhalational anthrax due to B. anthracis in combination with appropriate antibacterial drugs and, for prophy-
laxis of inhalational anthrax when alternative therapies are not available or are not appropriate.

Key Patent
Number: 8,617,548

Emergent Biosystems
Raxibacumab
Description
Raxibacumab is a human IgG1λ monoclonal antibody that binds the PA component of B. anthracis toxin. Raxibacumab has a molec-
ular weight of approximately 146 kilodaltons. Raxibacumab is produced by recombinant DNA technology in a murine cell expression
system.
Indications
Raxibacumab is indicated for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in com-
bination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available
or are not appropriate.

Key Patent
Number: 7,906,119

Endo International
Xiaflex
Description
Xiaflex contains purified collagenase clostridium histolyticum, consisting of two microbial collagenases in a defined mass ratio, Colla-
genase AUX-I and Collagenase AUX-II, which are isolated and purified from the fermentation of Clostridium histolyticum bacteria.
Collagenase AUX-I is a single polypeptide chain consisting of approximately 1000 amino acids of known sequence. It has an observed
molecular weight of 114 kiloDaltons (kDa). It belongs to the class I Clostridium histolyticum collagenases. Collagenase AUX-II is a
single polypeptide chain consisting of approximately 1000 amino acids of deduced sequence. It has an observed molecular weight of
113 kDa. It belongs to the class II Clostridium histolyticum collagenases.
Indications
Xiaflex is indicated for the treatment of adult patients with Dupuytren's contracture with a palpable cord and adult men with Peyro-
nie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.

Key Patent
Number:

9,512,216 expires 11/4/2025 - Use of TNFα inhibitor
8,906,373 expires 18/7/2023 - Use of TNF-alpha inhibitor for treatment of psoriasis
8,071,092 expires 10/3/2021 - Methods of inhibiting B lymphocytes using antibodies to Neutrokine-alpha

EUSA Pharma
Sylvant
Description
Siltuximab is a human-mouse chimeric monoclonal antibody that binds human interleukin-6 (IL-6) and is produced by Chinese
hamster ovary cells.
Indications
Sylvant is indicated for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency
virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Key Patent
Number: 7,291,721

10,717,781 expires 5/6/2029 - Neuroinvasion inhibitor
8,771,686 expires 22/11/2028 - Methods for treating a disease involving choroidal neovascularization by administering an IL-6 recep-
tor antibody
8,945,558 expires 2/11/2027 - Methods for treating myocardial infarction comprising administering an IL-6 inhibitor

Evolus
Jeuveau
800 30
700
25
600
20
500
400 15
300
10
200
5
100
5 5 5 5 5
4 4 3 3 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Jeuveau Median
Description
PrabotulinumtoxinA-xvfs is an acetylcholine release inhibitor and a neuromuscular blocking agent. PrabotulinumtoxinA-xvfs is sup-
plied as a sterile, vacuum-dried powder in a single-dose vial intended for intramuscular use after reconstitution. Prabotulinumtoxi-
nA-xvfs is a 900 kDa botulinum toxin type A, produced from fermentation of Clostridium botulinum .
Indications
Jeuveau is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator
and/or procerus muscle activity in adult patients.

Key Patent
Number: 9,512,418

Gilead
Trodelvy
Description
Sacituzumab govitecan-hziy is a Trop-2 directed antibody and topoisomerase inhibitor conjugate, composed of the following three
components: the humanized monoclonal antibody, hRS7 IgG1κ (also called sacituzumab), which binds to Trop-2 (the trophoblast
cell-surface antigen-2); the drug SN-38, a topoisomerase inhibitor; a hydrolysable linker (called CL2A), which links the humanized
monoclonal antibody to SN-38. The recombinant monoclonal antibody is produced by mammalian (murine myeloma) cells, while the
small molecule components SN-38 and CL2A are produced by chemical synthesis. Sacituzumab govitecan-hziy contains on average 7
to 8 molecules of SN-38 per antibody molecule. Sacituzumab govitecan-hziy has a molecular weight of approximately 160 kilodaltons.
Indications
Trodelvy is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic
therapies, at least one of them for metastatic disease.
Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and
either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

Key Patent
Number: 7,999,083

10,799,597 expires 9/10/2038 - Subcutaneous administration of antibody-drug conjugates for cancer therapy
10,918,734 expires 25/7/2038 - Treatment of high Trop-2 expressing triple negative breast cancer (TNBC) with sacituzumab govitecan
(IMMU-132) overcomes homologous recombination repair (HRR) rescue mediated by Rad51
10,266,605 expires 5/9/2037 - Efficacy of anti-trop-2-SN-38 antibody drug conjugates for therapy of tumors relapsed/refractory to
checkpoint inhibitors
10,954,305 expires 30/4/2037 - Combination of ABCG2 inhibitors with sacituzumab govitecan (IMMU-132) overcomes resistance to
SN-38 in Trop-2 expressing cancers
10,436,788 expires 6/9/2036 - Isolation, detection, diagnosis and/or characterization of circulating Trop-2-positive cancer cells
10,195,175 expires 23/6/2036 - Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative
breast cancer when used with microtubule inhibitors or PARP inhibitors
10,918,721 expires 30/12/2033 - Dosages of immunoconjugates of antibodies and SN-38 for improved efficacy and decreased toxicity
10,413,539 expires 13/11/2033 - Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan
(IMMU-132)
10,744,129 expires 2/10/2033 - Therapy of small-cell lung cancer (SCLC) with a topoisomerase-I inhibiting antibody-drug conjugate
(ADC) targeting Trop-2

GSK
Benlysta
1,600 30
1,400
25
1,200
20
1,000
800 15
15 15 15
600 14
12 12 12 10
400 10
8 8
5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Benlysta Median
Description
Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS, also referred
to as BAFF and TNFSF13B). Belimumab has a molecular weight of approximately 147 kDa. Belimumab is produced by recombinant
DNA technology in a murine cell (NS0) expression system.
Indications
Benlysta is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated for the treatment of: patients aged 5 years and older with
active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy; adult patients with active lupus
nephritis who are receiving standard therapy.

Key Patent
Number: 7,138,501

8,642,740 expires 11/10/2027 - Antibodies to lymphotoxin-alpha

Blenrep
3,500 30
3,000 25
2,500
20
2,000
15
1,500
12 12 12 12 12 12 10
1,000 10 10
8 8
500 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Blenrep Median
Description
Belantamab mafodotin-blmf is a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate. Be-
lantamab mafodotin-blmf is an antibody conjugate composed of 3 components: 1) afucosylated, humanized immunoglobulin G1
monoclonal antibody covalently linked to 2) the microtubule inhibitor MMAF via 3) a protease-resistant maleimidocaproyl linker.
The antibody is produced in a mammalian cell line (Chinese Hamster Ovary) using recombinant DNA technology and the microtu-
bule inhibitor and linker are produced by chemical synthesis. Approximately 4 molecules of mafodotin are attached to each antibody
molecule. The molecular weight of belantamab mafodotin-blmf is approximately 152 kDa.
Indications
Blenrep is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior
therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. This indication is
approved under accelerated approval based on response rate

Key Patent
Number: 9,273,141

Jemperli
1,000 30
900
25
800
700
20
600
500 15
400 14 14 14 14 14
13
10
300 11
9 9 9
200
5
100
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Jemperli Median
Description
Dostarlimab-gxly is a programmed death receptor-1 (PD-1)-blocking IgG 4 humanized monoclonal antibody. Dostarlimab-gxly is
produced in Chinese hamster ovary cells and has a calculated molecular weight of about 144 kDa.
Indications
Jemperli is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial
cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing
regimen. This indication is approved under accelerated approval based on tumor response rate and durability of response

Key Patent
Number: 9,815,897

Nucala
2,500 30
25
2,000
20
1,500
15
15
1,000
12 12 12 12 12 10
10
500 8 8 8
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Nucala Median
Description
Mepolizumab is a humanized IL-5 antagonist monoclonal antibody. Mepolizumab is produced by recombinant DNA technology in
Chinese hamster ovary cells. Mepolizumab has a molecular weight of approximately 149 kDa.
Indications
Nucala is an interleukin-5 (IL-5) antagonist monoclonal antibody (IgG1κ) indicated for:
Add-on maintenance treatment of patients with severe asthma aged 6 years and older, and with an eosinophilic phenotype.
The treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).
The treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) for =6 months without
an identifiable non hematologic secondary cause.

Key Patent
Number: 5,693,323

10,870,695 expires 22/8/2036 - Biopharmaceutical compositions comprising interleukin-5 antibody
9,834,600 expires 13/6/2032 - Methods of treatment of eosinophilic bronchitis with an anti-IL-5 antibody

Halozyme
Hylenex Recombinant
100 30
90
25
80
70
20
60
50 15
40
10
30
20
5
6 6 6 6 6
10 5 5 5 5
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Hylenex Median
Description
Hylenex recombinant is a purified preparation of the enzyme recombinant human hyaluronidase. Hylenex recombinant is produced
by genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human
hyaluronidase (PH20). The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of
61,000 Daltons.
Indications
Hylenex recombinant is an endoglycosidase indicated as :
an adjuvant in subcutaneous fluid administration for achieving hydration
to increase the dispersion and absorption of other injected drugs
in subcutaneous urography for improving resorption of radiopaque agents

Key Patent
Number: 7,767,429

10,865,400 expires 20/12/2034 - PH20 polypeptide variants, formulations and uses thereof
10,137,104 expires 15/3/2033 - Combination therapy with an anti-hyaluronan agent and therapeutic agent
9,750,752 expires 30/8/2032 - Subcutaneously administered anti-IL-6 receptor antibody
9,539,263 expires 23/5/2032 - Subcutaneously administered anti-IL-6 receptor antibody for treatment of systemic sclerosis
10,231,981 expires 18/11/2031 - Subcutaneously administered anti-IL-6 receptor antibody for treatment of juvenile idiopathic arthritis
10,265,410 expires 4/10/2031 - Adverse side-effects associated with administration of an anti-hyaluronan agent and methods for ame-
liorating or preventing the side-effects

9,284,543 expires 3/3/2031 - Neutral active soluble truncated PH20 polypeptides and uses thereof
8,927,249 expires 17/2/2031 - Extended soluble PH20 polypeptides and uses thereof
9,345,661 expires 27/7/2030 - Subcutaneous anti-HER2 antibody formulations and uses thereof
10,328,130 expires 14/4/2029 - Modified hyaluronidases and uses in treating hyaluronan-associated diseases and conditions
8,187,855 expires 6/3/2029 - Large-scale production of soluble hyaluronidase
9,775,889 expires 6/3/2029 - Methods of treatment of cellulite

Horizon Pharma
Krystexxa
2,000 30
1,800
25
1,600
1,400
20
1,200
1,000 15
800
10
600
9 9 9
400 8 8
5
6 6 6
200 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Krystexxa Median
Description
Krystexxa (pegloticase) is a uric acid specific enzyme which is a PEGylated product that consists of recombinant modified mammalian
urate oxidase (uricase) produced by a genetically modified strain of Escherichia coli. Uricase is covalently conjugated to monometh-
oxypoly (ethylene glycol) [mPEG] (10 kDa molecular weight). The cDNA coding for uricase is based on mammalian sequences. Each
uricase subunit has a molecular weight of approximately 34 kDa per subunit. The average molecular weight of pegloticase (tetrameric
enzyme conjugated to mPEG) is approximately 540 kDa.
Indications
Krystexxa (pegloticase) is a PEGylated uric acid specific enzyme indicated for the treatment of chronic gout in adult patients refracto-
ry to conventional therapy.

Key Patent
Number: 6,783,965

9,534,013 expires 10/9/2027 - Purification of proteins with cationic surfactant
8,148,123 expires 8/9/2027 - Methods for lowering elevated uric acid levels using intravenous injections of PEG-uricase
7,811,800 expires 11/4/2026 - Variant form of urate oxidase and use thereof

Tepezza
5,000 30
4,500
25
4,000
3,500
20
3,000
2,500 15
2,000
10
1,500
9 9 9
1,000 8 8
5
6 6 6
500 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Tepezza Median
Description
Teprotumumab-trbw, an insulin-like growth factor-1 receptor inhibitor (IGF-1R), is a fully human IgG1 monoclonal antibody pro-
duced in Chinese hamster ovary (CHO-DG44) cells. It has a molecular weight of approximately 148 kilodaltons.
Indications
Tepezza is indicated for the treatment of Thyroid Eye Disease.

Key Patent
Number: 7,572,897

Uplizna
1,400 30
1,200 25
1,000
20
800
15
600
10
400
9 9 9
8 8
200 5
6 6 6
5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Uplizna Median
Description
Inebilizumab-cdon is a CD19-directed humanized afucosylated IgG1 monoclonal antibody produced by recombinant DNA technolo-
gy in Chinese hamster ovary (CHO) cell suspension culture. The molecular weight is approximately 149 kDa.
Indications
Uplizna is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquapor-
in-4 (AQP4) antibody positive.

Key Patent
Number: 8,323,653

Innate Pharma
Lumoxiti
Description
Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin. Moxetumomab pasudotox-tdfk is composed of a recombinant, murine
immunoglobulin variable domain genetically fused to a truncated form of Pseudomonas exotoxin, PE38, that inhibits protein synthe-
sis. Moxetumomab pasudotox-tdfk has an approximate molecular weight of 63 kDa and is produced in E. coli cells by recombinant
DNA technology. During the moxetumomab pasudotox-tdfk manufacturing process, fermentation is carried out in nutrient medium
containing the antibiotic kanamycin.
Indications
Lumoxiti is indicated for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who received at least
two prior systemic therapies, including treatment with a purine nucleoside analog (PNA).

Key Patent
Number: 8,809,502

10,590,197 expires 15/7/2036 - Antibody molecules which bind CD22
10,370,447 expires 16/7/2035 - Molecules with specificity for CD79 and CD22

Ipsen
Increlex
35 30
30 25
25
20
20
15
15
10
10
9 9 9 9 9
5 7 5
6
4 4 2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Increlex Median
Description
Increlex (mecasermin) injection contains human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology.
IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 daltons.
The amino acid sequence of the product is identical to that of endogenous human IGF-1. The rhIGF-1 protein is synthesized in bacte-
ria ( E. coli ) that have been modified by the addition of the gene for human IGF-1.
Indications
Increlex (mecasermin) injection is indicated for the treatment of growth failure in pediatric patients 2 years of age and older with
severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Key Patent
Number: 5,681,814

8,108,149 expires 22/7/2029 - Method and device for diagnosing and treating insulin-like growth factor deficiency disorders
8,158,582 expires 11/7/2027 - Methods for treatment of insulin-like growth factor-1 deficiency
8,440,616 expires 1/6/2026 - Methods for treatment of insulin-like growth factor-1 deficiency
8,133,862 expires 31/3/2025 - Methods for treatment of insulin-like growth factor-1 (IGF-1) deficiency

Johnson and Johnson

Darzalex
30,000 30
25,000 25
24
20,000 22 20
20
15,000 15
16
10,000 12 10
5,000 5
6 6
4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Darzalex Median
Description
Daratumumab is an immunoglobulin G1κ (IgG1κ) human monoclonal antibody that binds to CD38 antigen. It is produced in Chi-
nese Hamster Ovary (CHO) cells using recombinant DNA technology. The molecular weight of daratumumab is approximately 148
kDa.
Indications
Darzalex is a CD38-directed cytolytic antibody indicated for the treatment of adult patients with multiple myeloma: in combination
with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in
patients with relapsed or refractory multiple myeloma who have received at least one prior therapy, in combination with bortezomib,
melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant, in combination with
bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant, in
combination with bortezomib and dexamethasone in patients who have received at least one prior therapy, in combination with
carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of
therapy, in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including
lenalidomide and a proteasome inhibitor, as monotherapy, in patients who have received at least three prior lines of therapy including
a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.

Key Patent
Number: 7,829,673

10,385,135 expires 1/11/2036 - Subcutaneous formulations of anti-CD38 antibodies and their uses
10,668,149 expires 22/6/2036 - Combination therapies for heme malignancies with anti-CD38 antibodies and survivin inhibitors
10,793,630 expires 2/12/2035 - Anti-CD38 antibodies for treatment of acute myeloid leukemia
10,106,620 expires 16/10/2035 - Blocking CD38 using anti-CD38 F(ab′)2 to protect NK cells
10,604,580 expires 8/9/2035 - Combination therapies with anti-CD38 antibodies
10,556,961 expires 24/2/2035 - Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia


9,249,226 expires 24/11/2031 - Antibodies against human CD38
9,040,050 expires 25/9/2029 - Combination treatment of CD38-expressing tumors
Darzalex Faspro
30,000 30
25,000 25
24
20,000 22 20
20
15,000 15
16
10,000 12 10
5,000 5
6 6
4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Darzalex Median
Description
Daratumumab is an immunoglobulin G1κ (IgG1κ) human monoclonal antibody that binds to the CD38 antigen. Daratumumab is
produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. The molecular weight of daratumumab is
approximately 148 kDa. Hyaluronidase (recombinant human) is an endoglycosidase used to increase the dispersion and absorption
of co-administered drugs when administered subcutaneously. It is a glycosylated single-chain protein produced by Chinese Hamster
Ovary cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (recombinant
human) has a molecular weight of approximately 61 kDa.
Indications
Darzalex FASPRO is a combination of daratumumab, a CD38-directed cytolytic antibody, and hyaluronidase, an endoglycosidase,
indicated for the treatment of adult patients with:
multiple myeloma in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for
autologous stem cell transplant
multiple myeloma in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autolo-
gous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
multiple myeloma in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for
autologous stem cell transplant
multiple myeloma in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
multiple myeloma in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of
therapy including lenalidomide and a proteasome inhibitor multiple myeloma as monotherapy, in patients who have received at least
three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a
PI and an immunomodulatory agent.
Light chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone in newly diagnosed patients.
This indication is approved under accelerated approval based on response rate.

Key Patent
Number: 7,829,673



10,106,620 expires 16/10/2035 - Blocking CD38 using anti-CD38 F(ab′)2 to protect NK cells
9,040,050 expires 25/9/2029 - Combination treatment of CD38-expressing tumors
9,187,565 expires 5/12/2027 - Antibodies against CD38 for treatment of multiple myeloma
Simponi
6,000 30
5,000 25
24
4,000 22 20
20
3,000 15
14
2,000 12 10
1,000 5
6 6
4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Simponi Median
Description
Golimumab is a human IgG1κ monoclonal antibody specific for human tumor necrosis factor α (TNFa) that exhibits multiple gly-
coforms with molecular masses of approximately 150 to 151 kilodaltons. Golimumab was created using genetically engineered mice
immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions. Golimumab is
produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to
inactivate and remove viruses.
Indications
Simponi is a tumor necrosis factor (TNF) blocker indicated for the treatment of adult patients with:
Moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate
Active psoriatic arthritis (PsA) alone, or in combination with methotrexate
Active ankylosing spondylitis (AS)
Moderate to severe Ulcerative colitis (UC) with an inadequate response or intolerant to prior treatment or requiring continuous ster-
oid therapy:
inducing and maintaining clinical response

improving endoscopic appearance of the mucosa during induction

inducing clinical remission
achieving and sustaining clinical remission in induction responders

Key Patent
Number: 7,691,378
Simponi Aria
6,000 30
5,000 25
24
4,000 22 20
20
3,000 15
14
2,000 12 10
1,000 5
6 6
4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Simponi Median
Description
Golimumab is a human IgG1κ monoclonal antibody specific for human tumor necrosis factor α (TNFa) that exhibits multiple gly-
coforms with molecular masses of approximately 150 to 151 kilodaltons. Golimumab was created using genetically engineered mice
immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions. Golimumab is
produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to
inactivate and remove viruses.
Indications
Simponi ARIA is a tumor necrosis factor (TNF) blocker indicated for the treatment of: Adult patients with moderately to severely
active Rheumatoid Arthritis (RA) in combination with methotrexate
Active Psoriatic Arthritis (PsA) in patients 2 years of age and older
Adult patients with active Ankylosing Spondylitis (AS)
Active polyarticular Juvenile Idiopathic Arthritis (pJIA) in patients 2 years of age and older

Key Patent
Number: 7,691,378


Stelara
14,000 30
12,000 25
10,000
20
8,000
15
6,000
13
12 10
4,000 11
8
2,000 5
6
3 3 2 2 2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Stelara Median
Description
Ustekinumab, a human IgG1κ monoclonal antibody, is a human interleukin-12 and -23 antagonist. Using DNA recombinant tech-
nology, ustekinumab is produced in a murine cell line (Sp2/0). The manufacturing process contains steps for the clearance of viruses.
Ustekinumab is comprised of 1326 amino acids and has an estimated molecular mass that ranges from 148,079 to 149,690 Daltons.
Indications
Stelara is a human interleukin-12 and -23 antagonist indicated for the treatment of:
Adult patients with: moderate to severe plaque psoriasis (Ps) who are candidates for phototherapy or systemic therapy.
active psoriatic arthritis (PsA) , alone or in combination with methotrexate.
moderately to severely active Crohn's disease (CD) .
moderately to severely active ulcerative colitis.
Pediatric patients 6 years and older with: moderate to severe plaque psoriasis , who are candidates for phototherapy or systemic thera-
py.

Key Patent
Number: 6,902,734

10,961,307 expires 24/9/2039 - Methods of treating moderately to severely active ulcerative colitis by administering an anti-IL12/IL23
antibody
9,725,522 expires 7/11/2023 - Pulmonary administration of immunoglobulin single variable domains and constructs thereof

Tremfya
9,000 30
8,000
25
7,000
6,000 20
5,000
15
4,000
3,000 12 10
11 11
2,000 8
7 5
1,000
3 3 2 2 2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Tremfya Median
Description
Guselkumab, an interleukin-23 blocker, is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody. Guselkumab is produced in
a mammalian cell line using recombinant DNA technology.
Indications
Tremfya is an interleukin-23 blocker indicated for the treatment of adult patients with:
moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy
active psoriatic arthritis.

Key Patent
Number: 7,935,344

10,507,241 expires 23/7/2035 - Biomarkers useful in the treatment of IL-23A related diseases
10,202,448 expires 2/11/2031 - Anti-IL-23 antibodies

Kyowa Kirin
Poteligeo
30,000 30
25,000 25
20,000 20
15,000 15
10,000 10
5,000 5
5 5 5 5 5
3 3 3 3 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Poteligeo Median
Description
Mogamulizumab-kpkc is a recombinant humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4)-expressing
cells. Mogamulizumab-kpkc is an IgG1κ immunoglobulin that has a calculated molecular mass of approximately 149 kDa. Mogamuli-
zumab-kpkc is produced by recombinant DNA technology in Chinese hamster ovary cells.
Indications
Poteligeo is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sezary syndrome (SS)
after at least one prior systemic therapy.

Key Patent
Number: 6,989,145

10,294,302 expires 8/7/2033 - Therapeutic method and medicament for HTLV-1 associated myelopathy

Lundbeck
Vyepti
8,000 30
7,000
25
6,000
20
5,000
4,000 15
3,000
10
2,000
8 8 8 8 8
7 5
1,000 6
5
4 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Vyepti Median
Description
Eptinezumab-jjmr is a humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for calcitonin gene-related peptide
(CGRP) ligand. Eptinezumab-jjmr has an approximate molecular weight of 143 kD. Eptinezumab-jjmr is produced in Pichia pastoris
yeast cells by recombinant DNA technology.
Indications
Vyepti is a calcitonin gene-related peptide antagonist indicated for the preventive treatment of migraine in adults

Key Patent
Number: 9,745,373

Macrogenics
Margenza
900 30
800
25
700
600 20
500
15
400
300 10
200 8
7 7 7 7 7 7 5
100 6
5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Margenza Median
Description
Margetuximab-cmkb, a HER2/neu receptor antagonist, is a chimeric Fc-engineered IgG1κ monoclonal antibody. Margetuximab-cmkb
is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Margetuximab-cmkb has an
approximate molecular weight of 149 kDa.
Indications
Margenza is indicated, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast
cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease

Key Patent
Number: 8,802,093

Mannkind
Afrezza
400 30
350
25
300
20
250
200 15
150
10
100
5
50
3 3 3 3 3 2 2 1 1 1
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Afrezza Median
Description
11.1 Afrezza Cartridges Afrezza consists of single-use plastic cartridges filled with a white powder containing insulin (human), which
is administered via oral inhalation using the Afrezza Inhaler only. Afrezza cartridges contain human insulin produced by recombinant
DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12).
Indications
Afrezza is a rapid acting inhaled insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Key Patent
Number: 8,551,528

10,561,806 expires 24/5/2038 - Mouthpiece cover for an inhaler
10,159,644 expires 30/6/2035 - Inhalable vaccine compositions and methods
10,421,729 expires 1/4/2035 - Microcrystalline diketopiperazine compositions and methods
9,925,144 expires 18/7/2034 - Heat-stable dry powder pharmaceutical compositions and methods
9,802,012 expires 13/7/2034 - Dry powder drug delivery system and methods
10,625,034 expires 1/5/2032 - Blister package for pharmaceutical cartridges
9,983,108 expires 18/10/2031 - Apparatus, system and method for measuring resistance of an inhaler
9,706,944 expires 25/8/2031 - Apparatus and method for simulating inhalation efforts
10,675,421 expires 26/12/2030 - Interactive apparatus and method for real-time profiling of inhalation efforts
Menarini
Elzonris
Description
Tagraxofusp-erzs, a CD123-directed cytotoxin, is a fusion protein comprised of a recombinant human interleukin-3 (IL-3) and trun-
cated diphtheria toxin (DT). Tagraxofusp-erzs has an approximate molecular weight of 57,695 Daltons. Tagraxofusp-erzs is construct-
ed by recombinant DNA technology and produced in Escherichia coli cells.
Indications
Elzonris is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in
pediatric patients 2 years and older.

Key Patent
Number: 9,181,317
Merck and Co
Follistim Aq
300 30
250 25
200 20
150 15
100 10
50 5
4 3 3 3 3 3 3 3 2 2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Follistim AQ Median
Description
Follistim AQ Cartridge contains human follicle-stimulating hormone (hFSH), a glycoprotein hormone which is manufactured by re-
combinant DNA (rDNA) technology. The active drug substance, follitropin beta, has a dimeric structure containing two glycoprotein
subunits (α and β). Both the 92 amino acid α-chain and the 111 amino acid β-chain have complex heterogeneous structures arising
from two N-linked oligosaccharide chains. Follitropin beta is synthesized in a Chinese hamster ovary (CHO) cell line that has been
transfected with a plasmid containing the two subunit DNA sequences encoding for hFSH.
Indications
Follistim AQ Cartridge is a gonadotropin indicated:
In Women for: Induction of Ovulation and Pregnancy in Anovulatory Infertile Women in Whom the Cause of Infertility is Function-
al and Not Due to Primary Ovarian Failure, Pregnancy in Normal Ovulatory Women Undergoing Controlled Ovarian Stimulation as
Part of an In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) Cycle.
In Men for: Induction of Spermatogenesis in Men with Primary and Secondary Hypogonadotropic Hypogonadism (HH) in Whom
the Cause of Infertility is Not Due to Primary Testicular Failure.

Key Patent
Number: 5,929,028
Keytruda
45,000 30
40,000
25
35,000
30,000 20
25,000
15
20,000
15,000 10
10 10 10 10
10,000 9
8
7 5
5,000 6 6
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Keytruda Median
Description
Pembrolizumab is a programmed death receptor-1 (PD 1)-blocking antibody. Pembrolizumab is a humanized monoclonal IgG4κ an-
tibody with an approximate molecular weight of 149 kDa. Pembrolizumab is produced in recombinant Chinese hamster ovary (CHO)
cells.
Indications
Keytruda is a programmed death receptor-1 (PD-1)-blocking antibody indicated:
for the treatment of patients with unresectable or metastatic melanoma.
for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
in combination with pemetrexed and platinum chemotherapy, as first-line treatment of patients with metastatic nonsquamous NS-
CLC, with no EGFR or ALK genomic tumor aberrations
in combination with carboplatin and either paclitaxel or paclitaxel protein-bound as first-line treatment of patients with metastatic
squamous NSCLC, as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score
(TPS) =1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is: stage III where pa-
tients are not candidates for surgical resection or definitive chemoradiation, or metastatic
as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS =1%) as determined by an
FDA-approved test, with disease progression on or after platinum-containing chemotherapy.
Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberra-
tions prior to receiving Keytruda.
Head and Neck Squamous Cell Cancer (HNSCC):
in combination with platinum and FU for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC.
as a single agent for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express
PD-L1 [Combined Positive Score (CPS) =1] as determined by an FDA-approved test.
as a single agent for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-con-
taining chemotherapy.
Classical Hodgkin Lymphoma (cHL):
for the treatment of adult patients with relapsed or refractory cHL.
for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma (PMBCL):
for the treatment of adult and pediatric patients with refractory PMBCL, or who have relapsed after 2 or more prior lines of therapy.
for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing
chemotherapy and whose tumors express PD-L1 [Combined Positive Score (CPS) =10] as determined by an FDA-approved test, or in
patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or
following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy.
for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer
(NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystec-
tomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer for the treatment of adult and pediatric patients with unresect-
able or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed
following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC) for the treatment of patients with unresectable
or metastatic MSI-H or dMMR colorectal cancer (CRC).
Gastric Cancer:
in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients
with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
as a single agent for the treatment of patients with recurrent locally advanced or metastatic gastric or GEJ adenocarcinoma whose
tumors express PD-L1 [Combined Positive Score (CPS) =1] as determined by an FDA-approved test, with disease progression on or
after 2 or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/
neu-targeted therapy.
Esophageal Cancer for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ)
(tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemo-
radiation either: in combination with platinum- and fluoropyrimidine-based chemotherapy, or as a single agent after one or more
prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS =10) as determined by an
FDA-approved test.
Cervical Cancer for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemo-
therapy whose tumors express PD-L1 [Combined Positive Score (CPS) =1] as determined by an FDA-approved test.
Hepatocellular Carcinoma (HCC) for the treatment of patients with HCC who have been previously treated with sorafenib.
Merkel Cell Carcinoma (MCC) for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel
cell carcinoma.
Renal Cell Carcinoma (RCC) in combination with axitinib, for the first-line treatment of patients with advanced RCC.
Endometrial Carcinoma in combination with lenvatinib, for the treatment of patients with advanced endometrial carcinoma that is
not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for cura-
tive surgery or radiation.
Tumor Mutational Burden-High (TMB-H) Cancer for the treatment of adult and pediatric patients with unresectable or metastatic
tumor mutational burden-high (TMB-H) [=10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test,
that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Cutaneous Squamous Cell Carcinoma (cSCC) for the treatment of patients with recurrent or metastatic cSCC or locally advanced
cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer (TNBC) in combination with chemotherapy, for the treatment of patients with locally recurrent unre-
sectable or metastatic TNBC whose tumors express PD-L1 [Combined Positive Score (CPS) =10] as determined by an FDA approved
test.

Key Patent
Number: 8,354,509

10,414,747 expires 2/10/2037 - Benzo[b]thiophene compounds as sting agonists
10,392,442 expires 12/4/2037 - Use of anti-PD-1 antibody in combination with anti-CD27 antibody in cancer treatment
10,945,990 expires 27/6/2036 - Combination of a PD-1 antagonist and eribulin for treating cancer
10,695,426 expires 25/10/2035 - Combination of a PD-1 antagonist and an ALK inhibitor for treating cancer
10,570,202 expires 3/2/2035 - Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer
9,827,309 expires 15/8/2034 - Treating cancer with a combination of a PD-1 antagonist and dinaciclib
Pegintron
Description
Sylatron, peginterferon alfa-2b, is a covalent conjugate of recombinant alfa-2b interferon with monomethoxy polyethylene glycol
(PEG). The average molecular weight of the PEG portion of the molecule is 12,000 daltons. The average molecular weight of the
Sylatron molecule is approximately 31,000 daltons. The specific activity of pegylated interferon alfa-2b is approximately 0.7 x 10^8
international units/mg protein. Interferon alfa-2b is a protein with a molecular weight of 19,271 daltons produced by recombinant
DNA techniques. It is obtained from the bacterial fermentation of a strain of Escherichia coli bearing a genetically engineered plasmid
containing an interferon gene from human leukocytes.
Indications
Sylatron is an α interferon indicated for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84
days of definitive surgical resection including complete lymphadenectomy.

Key Patent
Number: 6,180,096

8,679,472 expires 2/5/2028 - Crystal of human interferon alpha 2B in complex with zinc
7,632,491 expires 13/4/2028 - Stable pegylated interferon formulation
Zinplava
Description
Bezlotoxumab is a human monoclonal antibody that binds to C. difficile toxin B and neutralizes its effects. Bezlotoxumab is an IgG 1
immunoglobulin with an approximate molecular weight of 148.2 kDa.
Indications
Zinplava is indicated to reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiv-
ing antibacterial drug treatment of CDI and are at a high risk for CDI recurrence.

Key Patent
Number: 8,257,709

9,181,632 expires 8/9/2034 - C.difficile toxin B CROP domain peptides, antibodies and complexes thereof
Merck KGaA
Bavencio
2,500 30
25
2,000
20
1,500
15
1,000
10
9
500 8 8 8 8 8
7 5
5 5
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Bavencio Median
Description
Avelumab is a programmed death ligand1 (PD-L1) blocking antibody. Avelumab- is a human IgG1 λ monoclonal antibody produced
in Chinese hamster ovary cells and has a molecular weight of approximately 147 kDa.
Indications
Bavencio is a programmed death ligand-1 (PD-L1) blocking antibody indicated for:
Merkel Cell Carcinoma (MCC) Adults and pediatric patients 12 years and older with metastatic MCC. This indication is approved
under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in confirmatory trials.
Urothelial Carcinoma (UC):
Maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing
chemotherapy.
Patients with locally advanced or metastatic UC who:
Have disease progression during or following platinum-containing chemotherapy.
Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Renal Cell Carcinoma (RCC) First-line treatment, in combination with axitinib, of patients with advanced RCC.

Key Patent
Number: 9,624,298

10,759,856 expires 25/2/2034 - Anti-PD-L1 antibodies and uses thereof
Gonal-F
2,500 30
25
2,000
20
1,500
15
16 16 16 16 16
1,000 14 14
10
10 10
500 8
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Gonal-F Median
Description
GONAL-F RFF (follitropin alpha for injection) is a gonadotropin [human follicle stimulating hormone (FSH)], a glycoprotein hor-
mone manufactured by recombinant DNA technology. The active drug substance, follitropin alfa, has a dimeric structure consisting
of two non-covalently linked, non-identical glycoproteins designated as the α- and β-subunits. The α- and β-subunits have 92 and
111 amino acids, respectively, and their primary and tertiary structure are indistinguishable from those of human follicle stimulat-
ing hormone. Recombinant human FSH production occurs in genetically modified Chinese Hamster Ovary (CHO) cells cultured in
bioreactors.
Indications
Gonal-F RFF is indicated for:
Induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due
to primary ovarian failure.
Development of multiple follicles in ovulatory infertile women as part of Assisted Reproductive Technology (ART) cycles.

Key Patent
Number: 5,156,957

7,700,112 expires 7/6/2027 - FSH beta mutants that are glycosilated at residues N55 and T57
Gonal-F RFF
2,500 30
25
2,000
20
1,500
15
16 16 16 16 16
1,000 14 14
10
10 10
500 8
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Gonal-F Median
Description
GONAL-F RFF (follitropin alpha for injection) is a gonadotropin [human follicle stimulating hormone (FSH)], a glycoprotein hor-
mone manufactured by recombinant DNA technology. The active drug substance, follitropin alfa, has a dimeric structure consisting
of two non-covalently linked, non-identical glycoproteins designated as the α- and β-subunits. The α- and β-subunits have 92 and
111 amino acids, respectively, and their primary and tertiary structure are indistinguishable from those of human follicle stimulat-
ing hormone. Recombinant human FSH production occurs in genetically modified Chinese Hamster Ovary (CHO) cells cultured in
bioreactors.
Indications
Gonal-F RFF is indicated for:
Induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due
to primary ovarian failure.
Development of multiple follicles in ovulatory infertile women as part of Assisted Reproductive Technology (ART) cycles.

Key Patent
Number: 5,767,251

Ovidrel
Description
Ovidrel PreFilled Syringe (choriogonadotropin alfa injection) is a sterile liquid preparation of choriogonadotropin alfa (recombinant
human Chorionic Gonadotropin, r-hCG). Choriogonadotropin alfa is a water soluble glycoprotein consisting of two non-covalently
linked subunits - designated α and β - consisting of 92 and 145 amino acid residues, respectively, with carbohydrate moieties linked
to ASN-52 and ASN-78 (on α subunit) and ASN-13, ASN-30, SER-121, SER-127, SER-132 and SER-138 (on β subunit). The primary
structure of the a - chain of r-hCG is identical to that of the a - chain of hCG, FSH and LH. The glycoform pattern of the a - subunit
of r-hCG is closely comparable to urinary derived hCG (u-hCG), the differences mainly being due to the branching and sialylation
extent of the oligosaccharides. The β - chain has both O- and N-glycosylation sites and its structure and glycosylation pattern are also
very similar to that of u-hCG.
Indications
Ovidrel is indicated for the induction of final follicular maturation and early luteinization in infertile women who have undergone
pituitary desensitization and who have been appropriately pretreated with follicle stimulating hormones as part of an Assisted Repro-
ductive Technology (ART) program such as in vitro fertilization and embryo transfer. Ovidrel is also indicated for the induction of
ovulation (OI) and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary
ovarian failure.

Key Patent
Number: 5,767,251

Rebif
1,200 30
1,000 25
800 20
600 15
400 10
11 11
8 8 8
200 7 7 7 5
5
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Rebif Median
Description
Rebif (interferon beta-1a) is a purified 166 amino acid glycoprotein with a molecular weight of approximately 22,500 daltons. It is pro-
duced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon
beta gene has been introduced. The amino acid sequence of Rebif is identical to that of natural fibroblast derived human interferon
beta. Natural interferon beta and interferon beta-1a (Rebif) are glycosylated with each containing a single N-linked complex carbohy-
drate moiety.
Indications
Rebif is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-re-
mitting disease, and active secondary progressive disease, in adults.

Key Patent
Number: 6,852,314
Serostim
Description
Zorbtive (somatropin) for injection is a human growth hormone produced by recombinant DNA technology for subcutaneous use.
Zorbtive has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical
to the dominant form of human pituitary growth hormone. Zorbtive is produced by a mammalian cell line (mouse C127) that has
been modified by the addition of the human growth hormone gene. Zorbtive is secreted directly through the cell membrane into the
cell-culture medium for collection and purification.
Indications
Zorbtive is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.

Key Patent
Number: 5,288,703
Morphosys
Monjuvi
1,800 30
1,600
25
1,400
1,200 20
1,000
15
800
600 10
400
5
200
4 4 3 3 3 3 3 3 3 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Monjuvi Median
Description
Tafasitamab-cxix is a humanized CD19-directed cytolytic monoclonal antibody that contains an IgG1/2 hybrid Fc-domain with 2
amino acid substitutions to modify the Fc-mediated functions of the antibody. It is produced by recombinant DNA technology in
mammalian cells (Chinese hamster ovary). Tafasitamab-cxix has a molecular weight of approximately 150 kDa.
Indications
Monjuvi, in combination with lenalidomide, is indicated for the treatment of adult patients with relapsed or refractory diffuse large
B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for
autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate

Key Patent
Number: 8,524,867
Nestle Health
Zenpep
Description
Zenpep is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase
contains multiple enzyme classes, including porcine-derived lipases, proteases, and amylases.
Indications
Zenpep is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.

Key Patent
Number: 7,658,918

8,246,950 expires 16/2/2031 - Stable digestive enzyme compositions
8,221,747 expires 25/1/2031 - Stable pancreatic enzyme compositions
Novartis
Adakveo
1,600 30
1,400
25
1,200
20
1,000
800 15
600 14 14 14 14 14
12 10
11
400 9 9
7 5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Adakveo Median
Description
Crizanlizumab-tmca is a P-selectin blocker humanized IgG2κ monoclonal antibody that binds to P-selectin. Crizanlizumab-tmca is
produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is composed of 2 heavy chains, each contain-
ing 448 amino acids, and 2 light chains each containing 218 amino acids, with a theoretical molecular weight of approximately 146
kDa.
Indications
Adakveo is indicated to reduce the frequency of vasoocclusive crises (VOCs) in adults and pediatric patients aged 16 years and older
with sickle cell disease.

Key Patent
Number: 8,377,440
Beovu
1,400 30
1,200 25
1,000
20
800
15
600 15 15
14 14 14
13
10
400 11
10
9
8
200 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Beovu Median
Description
Brolucizumab-dbll is a recombinant human vascular endothelial growth factor inhibitor. Brolucizumab-dbll is a humanized mon-
oclonal single-chain Fv (scFv) antibody fragment. Brolucizumab-dbll has a molecular weight of ~26 kilodaltons and is produced in
Escherichia coli cells by recombinant DNA technology.
Indications
Beovu is indicated for the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD).

Key Patent
Number: 8,349,322

10,689,438 expires 29/6/2036 - Stable protein solution formulation containing high concentration of an anti-VEGF antibody
10,035,850 expires 6/11/2035 - Methods for treating neovascular age-related macular degeneration
Cosentyx
9,000 30
8,000
25
7,000
6,000 20
5,000
15
4,000
14 14 14 14 14
3,000 12 12 10
2,000 9 9
8
5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Cosentyx Median
Description
Secukinumab, a recombinant human monoclonal IgG1/κ antibody, is an interleukin-17A antagonist. It is expressed in a recombinant
Chinese Hamster Ovary (CHO) cell line. Secukinumab has a molecular mass of approximately 151 kDa; both heavy chains of secuki-
numab contain oligosaccharide chains.
Indications
Cosentyx is a human interleukin-17A antagonist indicated for the treatment of:
moderate to severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy
adults with active psoriatic arthritis (PsA)
adults with active ankylosing spondylitis (AS)
adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation

Key Patent
Number: 7,807,155

9,717,791 expires 8/4/2032 - Methods of treating psoriasis using IL-17 antibody
10,583,190 expires 28/10/2031 - Methods of treating psoriasis using IL-17 antibodies
Ilaris
2,000 30
1,800
25
1,600
1,400
20
1,200
1,000 15
800 14 14
13 13 13
10
600 11
10
9
400 8 8
5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Ilaris Median
Description
Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is ex-
pressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains,
with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains
linked to the protein backbone at asparagine 298 (Asn 298).
Indications
Ilaris is an interleukin-1β blocker indicated for the treatment of:
Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children 4 years of age and older, including: Familial Cold Auto-in-
flammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS).
Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients.
Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients.
Familial Mediterranean Fever (FMF) in adult and pediatric patients.
Active Still's disease, including Adult-Onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2
years and older.

Key Patent
Number: 7,446,175

8,623,367 expires 9/12/2029 - Antibody formulation
Kesimpta
6,000 30
5,000 25
4,000 20
3,000 15
13 13 13 13 13
2,000 10
11
10
9 9
1,000 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Kesimpta Median
Description
Ofatumumab is a recombinant human monoclonal immunoglobulin G1 (IgG1) antibody that binds to human CD20 expressed on
B-cells. Ofatumumab is produced in a murine NS0 cell line and consists of two IgG1 heavy chains and two κ light chains with a molec-
ular weight of approximately 146 kDa.
Indications
Kesimpta is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relaps-
ing-remitting disease, and active secondary progressive disease, in adults.

Key Patent
Number: 7,682,612

10,640,572 expires 29/7/2035 - Anti-CD3 antibodies and methods of use
8,883,980 expires 5/10/2029 - Antigen binding molecules with increased Fc receptor binding affinity and effector function
Novo Nordisk
Fiasp
7,000 30
6,000 25
5,000
20
4,000
15
3,000 15 15 15
14 14 14
12 10
2,000 10
1,000 7 5
5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts FIASP Median
Description
Fiasp (insulin aspart injection) is a rapid-acting insulin analog for subcutaneous or intravenous administration used to lower blood
glucose. Insulin aspart is homologous with regular human insulin with the exception of a single substitution of the amino acid proline
by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae . Insulin aspart
has the empirical formula C 256 H 381 N 65 0 79 S 6 and a molecular weight of 5825.8 daltons.
Indications
Fiasp is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

Key Patent
Number: 8,324,157
Levemir
8,000 30
7,000
25
6,000
20
5,000
4,000 17 15
16 16 16 16 16
3,000 14
12 10
2,000 9
7 5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Levemir Median
Description
Levemir (insulin detemir injection) is a solution for subcutaneous use. Insulin detemir is a long-acting recombinant human insulin
analog. Levemir is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by
chemical modification. Insulin detemir differs from human insulin in that the amino acid threonine in position B30 has been omitted,
and a C14 fatty acid chain has been attached to the amino acid B29.
Indications
Levemir is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. Limitations of Use Levemir is
not recommended for the treatment of diabetic ketoacidosis. Levemir is a long-acting human insulin analog indicated to improve gly-
cemic control in adult and pediatric patients with diabetes mellitus ( 1 ). Limitations of Use: Not recommended for treating diabetic
ketoacidosis.

Key Patent
Number: 5,750,497

10,335,464 expires 27/6/2038 - Device for titrating basal insulin
10,040,839 expires 26/2/2035 - Insulin derivatives and the medical uses hereof
10,137,172 expires 30/4/2034 - Administration regime
10,596,229 expires 27/10/2031 - Method of treating diabetes mellitus by administration, at specifically defined intervals, of a derivative
of a naturally occurring insulin or insulin analogue, the derivative having a prolonged profile of action
9,603,904 expires 27/9/2030 - Treating diabetes melitus using insulin injections with less than daily injection frequency
9,260,501 expires 20/3/2030 - Peptide extended insulins
8,933,021 expires 22/1/2030 - Insulin derivative
9,034,818 expires 12/6/2028 - Pharmaceutical formulations comprising an insulin derivative
8,722,620 expires 10/2/2028 - Insulin derivatives
8,097,584 expires 14/11/2026 - Stabilized formulations of insulin that comprise ethylenediamine
7,595,172 expires 12/9/2026 - Method for making acylated polypeptides
7,402,565 expires 11/11/2024 - Processes for making acylated insulin

8,828,923 expires 22/7/2024 - Insulin derivatives
8,835,132 expires 9/9/2022 - Method for making acylated polypeptides
7,446,091 expires 30/4/2021 - Methods and preparations for curing clinically ill patients
Norditropin
10,000 30
9,000
25
8,000
7,000
20
6,000
5,000 15
16 16
15 15 15 15
4,000
13
10
3,000 11
2,000 8
5
6
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Norditropin Median
Description
Norditropin (somatropin) for injection is a recombinant human growth hormone. It is a polypeptide of recombinant DNA origin and
is synthesized by a special strain of E. coli bacteria that has been modified by the addition of a plasmid which carries the gene for hu-
man growth hormone. Norditropin contains the identical sequence of 191 amino acids constituting the naturally occurring pituitary
human growth hormone with a molecular weight of about 22,000 Daltons.
Indications
Pediatric Patients Norditropin is indicated for the treatment of pediatric patients with: growth failure due to inadequate secretion of
endogenous growth hormone (GH), short stature associated with Noonan syndrome, short stature associated with Turner syn-
drome, short stature born small for gestational age (SGA) with no catch-up growth by age 2 years to 4 years of age, Idiopathic Short
Stature (ISS), height standard deviation score (SDS) less than -2.25, and associated with growth rates unlikely to permit attainment of
adult height in the normal range, growth failure due to Prader-Willi syndrome (PWS).
Adult Patients Norditropin is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD)

Key Patent
Number: 8,841,252
Novolog
50,000 30
45,000
27 25
40,000
35,000
20
21
30,000
25,000 15
20,000
10
15,000
10,000
5
5,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts NovoMix Median
Description
Insulin aspart is a rapid-acting human insulin analog homologous with regular human insulin with the exception of a single substi-
tution of the amino acid proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Sac-
charomyces cerevisiae (baker's yeast). Insulin aspart has the empirical formula C 256 H 381 N 65 0 79 S 6 and a molecular weight of
5825.8 Da. In vitro assay confirms the minimum potency of insulin aspart to be NLT 15 units/mg. Figure 1. Structural formula of
insulin aspart. Novolog (insulin aspart) injection is a sterile, clear, and colorless solution for subcutaneous or intravenous use. Each
mL contains 100 units of insulin aspart and the inactive ingredients: disodium hydrogen phosphate dihydrate (1.25 mg), glycerin (16.0
mg), metacresol (1.72 mg), phenol (1.50 mg), sodium chloride (0.58 mg), zinc (19.6 mcg), and Water for Injection, USP. Novolog has a
pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium hydroxide 10% may be added to adjust pH. Fig. 1 - Structural Formula of Insulin
Aspart
Indications
Novolog is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

Key Patent
Number: 5,618,913

10,919,949 expires 25/9/2038 - Acylated insulin analogues and uses thereof
Novolog Mix 70/30

50,000 30
45,000
27 25
40,000
35,000
20
21
30,000
25,000 15
20,000
10
15,000
10,000
5
5,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts NovoMix Median
Description
Insulin aspart protamine and insulin aspart is a human insulin analog containing 70% insulin aspart protamine crystals and 30% sol-
uble insulin aspart. Insulin aspart is homologous with regular human insulin with the exception of a single substitution of the amino
acid proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae
(baker's yeast).
Indications
Insulin Aspart Protamine and Insulin Aspart Injectable Suspension Mix 70/30 is indicated to improve glycemic control in patients
with diabetes mellitus.

Key Patent
Number: 5,618,913

10,919,949 expires 25/9/2038 - Acylated insulin analogues and uses thereof
Sogroya
9,000 30
8,000
25
7,000
6,000 20
5,000
15
4,000
3,000 10
2,000 8 8
7 7 7 5
1,000 6 6
5
4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Sogroya Median
Description
Somapacitan-beco is a human growth hormone (hGH) analog with a single substitution in the amino acid backbone (L101C) to which
an albumin-binding moiety has been attached. The albumin-binding moiety (side-chain) consists of an albumin binder and a hydro-
philic spacer attached to position 101 of the protein. The protein part consists of 191 amino acids. Somapacitan-beco is produced in
Escherichia coli by recombinant DNA technology.
Indications
Sogroya is indicated for the replacement of endogenous growth hormone (GH) in adults with growth hormone deficiency (GHD).

Key Patent
Number: 8,779,109
Tresiba
25,000 30
25
20,000
20
15,000
17 17 17 17 17 15
16
10,000 14
12 10
9
5,000
7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Tresiba Median
Description
Tresiba (insulin degludec injection) is a long-acting basal human insulin analog for subcutaneous injection. Insulin degludec is
produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification.
Insulin degludec differs from human insulin in that the amino acid threonine in position B30 has been omitted and a side-chain con-
sisting of glutamic acid and a C16 fatty acid has been attached (chemical name: LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human
insulin). Insulin degludec has a molecular formula of C 274 H 411 N 65 O 81 S 6 and a molecular weight of 6103.97.
Indications
Tresiba is indicated to improve glycemic control in patients 1 year of age and older with diabetes mellitus.

Key Patent
Number: 7,615,532

10,335,464 expires 27/6/2038 - Device for titrating basal insulin
10,137,172 expires 30/4/2034 - Administration regime
10,596,229 expires 27/10/2031 - Method of treating diabetes mellitus by administration, at specifically defined intervals, of a derivative
of a naturally occurring insulin or insulin analogue, the derivative having a prolonged profile of action
9,603,904 expires 27/9/2030 - Treating diabetes melitus using insulin injections with less than daily injection frequency
Xultophy 100/3.6
9,000 30
8,000
25
7,000
6,000 20
5,000
17 17 17 17 17 15
4,000 16
14
3,000 12 10
2,000 9
7 5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Xultophy Median
Description
Xultophy 100/3.6 (insulin degludec and liraglutide injection), for subcutaneous use, is a combination of a long-acting basal human
insulin analog, insulin degludec, and a GLP-1 receptor agonist, liraglutide. Insulin degludec Insulin degludec is a long-acting basal hu-
man insulin analog. Insulin degludec is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevi-
siae followed by chemical modification. Insulin degludec differs from human insulin in that the amino acid threonine in position B30
has been omitted and a side-chain consisting of glutamic acid and a C16 fatty acid has been attached (chemical name: LysB29(Nε-hex-
adecandioyl-γ-Glu) des(B30) human insulin).
Indications
Xultophy 100/3.6 is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.

Key Patent
Number: 8,937,042
Oxurion
Jetrea
Description
Ocriplasmin is a recombinant truncated form of human plasmin with a molecular weight of
27.2 kDa produced by recombinant DNA technology in a Pichia pastoris expression system.
Indications
Jetrea is a proteolytic enzyme indicated for the treatment of symptomatic
vitreomacular adhesion.

Key Patent
Number: 7,445,775
Pfizer
Besponsa
450 30
400
25
350
300 20
250
15
200
150 10
100
5
50
2 2 2 2 2 1 1 1 1 1
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Besponsa Median
Description
11. DESCRIPTION Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate (ADC) consisting of 3 components:
1) the recombinant humanized immunoglobulin class G subtype 4 (IgG4) κ antibody inotuzumab, specific for human CD22, 2)
N-acetyl-γ-calicheamicin that causes double-stranded DNA breaks, and 3) an acid-cleavable linker composed of the condensation
product of 4-(4'-acetylphenoxy)-butanoic acid (AcBut) and 3-methyl-3-mercaptobutane hydrazide (known as dimethylhydrazide) that
covalently attaches N-acetyl-γ-calicheamicin to inotuzumab. Inotuzumab ozogamicin has an approximate molecular weight of 160
kDa. The average number of calicheamicin derivative molecules conjugated to each inotuzumab molecule is approximately 6 with a
distribution from 2-8. Inotuzumab ozogamicin is produced by chemical conjugation of the antibody and small molecule components.
The antibody is produced by mammalian (Chinese hamster ovary) cells, and the semisynthetic calicheamicin derivative is produced
by microbial fermentation followed by synthetic modification.
Indications
Besponsa is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Key Patent
Number: 8,153,768

10,370,447 expires 16/7/2035 - Molecules with specificity for CD79 and CD22
Elelyso
Description
Taliglucerase alfa is a hydrolytic lysosomal glucocerebroside-specific enzyme produced by recombinant DNA technology using plant
cell culture (carrot). Taliglucerase alfa is a monomeric glycoprotein enzyme containing 4 N-linked glycosylation sites (kDa=60.8).
Taliglucerase alfa differs from native human glucocerebrosidase by two amino acids at the N terminal and up to 7 amino acids at the
C terminal. Taliglucerase alfa is a glycosylated protein with oligosaccharide chains at the glycosylation sites having terminal mannose
sugars. These mannose-terminated oligosaccharide chains of taliglucerase alfa are specifically recognized by endocytic carbohydrate
receptors on macrophages, the cells that accumulate lipid in Gaucher disease.
Indications
Elelyso is indicated for the treatment of patients 4 years and older with a confirmed diagnosis of Type 1 Gaucher disease.

Key Patent
Number: 7,951,557

10,364,413 expires 29/1/2032 - Large scale disposable bioreactor
Mylotarg
Description
11. DESCRIPTION Gemtuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of the CD33-directed monoclonal an-
tibody (hP67.6; recombinant humanized immunoglobulin [Ig] G4, κ antibody produced by mammalian cell culture in NS0 cells) that
is covalently linked to the cytotoxic agent N-acetyl γ calicheamicin. Gemtuzumab ozogamicin consists of conjugated and unconjugat-
ed gemtuzumab. The conjugated molecules differ in the number of activated calicheamicin derivative moieties attached to gemtu-
zumab. The number of conjugated calicheamicin derivatives per gemtuzumab molecule ranges from predominantly zero to 6, with an
average of 2 to 3 moles of calicheamicin derivative per mole of gemtuzumab.
Indications
Mylotarg is a CD33-directed antibody and cytotoxic drug conjugate indicated for:
treatment of newly-diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients 1 month and older
treatment of relapsed or refractory CD33-positive AML in adults and pediatric patients 2 years and older

Key Patent
Number: 5,773,001

8,969,526 expires 24/4/2032 - Antibody Fc variants
8,546,549 expires 17/8/2029 - Processes for the convergent synthesis of calicheamicin derivatives
7,727,968 expires 5/6/2024 - Combination therapy for the treatment of acute leukemia and myelodysplastic syndrome
Somavert
450 30
400
25
350
300 20
250
15
200
150 10
100
5
50 6 6 6 6 6
4 4 3 2 2
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Somavert Median
Description
Somavert contains pegvisomant, an analog of human growth hormone (GH) that has been structurally altered to act as a GH receptor
antagonist. Pegvisomant is a protein of recombinant DNA origin containing 191 amino acid residues to which several polyethylene
glycol (PEG) polymers are covalently bound (predominantly 4 to 6 PEG/protein molecule). The molecular weight of the protein of
pegvisomant is 21,998 Daltons. The molecular weight of the PEG portion of pegvisomant is approximately 5000 Daltons. The predom-
inant molecular weights of pegvisomant are thus approximately 42,000, 47,000, and 52,000 Daltons. The schematic shows the amino
acid sequence of the pegvisomant protein (PEG polymers are shown attached to the 5 most probable attachment sites). Pegvisomant is
synthesized by a specific strain of Escherichia coli bacteria that has been genetically modified by the addition of a plasmid that carries
a gene for GH receptor antagonist. Biological potency is determined using a cell proliferation bioassay. Binding of Somavert to the GH
receptor results in disruption of the proper binding of the second GH receptor with inhibition of functional receptor dimerization and
subsequent intracellular signaling.
Indications
Somavert is indicated for the treatment of acromegaly in patients who have had an inadequate response to surgery or radiation thera-
py, or for whom these therapies are not appropriate.

Key Patent
Number: 5,849,535

6,838,075 expires 7/8/2021 - Inhaleable spray dried 4-helix bundle protein powders having minimized aggregation
Regeneron
Arcalyst
Description
Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleu-
kin-1 receptor component (IL-1R1) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the Fc portion of human IgG1.
Rilonacept has a molecular weight of approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO)
cells.
Indications
Arcalyst (rilonacept) is an interleukin-1 blocker indicated for:
Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS), and
Muckle-Wells Syndrome (MWS) in adults and children 12 years and older
Maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg
or more
Treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and children 12 years and older

Key Patent
Number: 5,844,099

6,472,179 expires 19/5/2019 - Receptor based antagonists and methods of making and using
Dupixent
20,000 30
18,000
25
16,000
14,000
20
12,000
10,000 15
8,000
12 12 12 12 12 12 10
6,000
10
4,000 8 8
5
6
2,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Dupixent Median
Description
Dupilumab, an interleukin-4 receptor α antagonist, is a human monoclonal antibody of the IgG4 subclass that binds to the IL-4Ra
subunit and inhibits IL-4 and IL-13 signaling. Dupilumab has an approximate molecular weight of 147 kDa. Dupilumab is produced
by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture.
Indications
Dupixent is indicated for the following diseases:
for the treatment of patients aged 6 years and older with moderate-to-severe atopic dermatitis whose disease is not adequately con-
trolled with topical prescription therapies or when those therapies are not advisable. Dupixent can be used with or without topical
corticosteroids.
as an add-on maintenance treatment in patients with moderate-to-severe asthma aged 12 years and older with an eosinophilic pheno-
type or with oral corticosteroid dependent asthma.
as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis (CR-
SwNP).

Key Patent
Number: 7,608,693

10,815,305 expires 29/1/2038 - Methods of treating inflammatory conditions
10,485,844 expires 21/9/2037 - Methods for treating severe atopic dermatitis by administering an IL-4R inhibitor
10,314,904 expires 17/2/2037 - Methods for enhancing efficacy of a vaccine by administering an IL-4R antagonist
10,137,193 expires 5/2/2036 - Methods for treating or preventing asthma by administering an IL-4R antagonist
10,066,017 expires 21/1/2036 - Methods for treating chronic sinusitis with nasal polyps by administering an IL-4R antagonist
10,370,449 expires 26/2/2035 - Methods for treating skin infection by administering an IL-4R antagonist
10,392,439 expires 13/10/2034 - Methods for treating allergy and enhancing allergen-specific immunotherapy by administering an
IL-4R inhibitor
10,669,341 expires 1/8/2034 - Methods for treating allergy and enhancing allergen-specific immunotherapy by administering an anti-
body to IL-4 receptor
10,676,530 expires 29/7/2034 - Methods for treating allergy and enhancing allergen-specific immunotherapy by administering an
antibody to IL-4 receptor
10,730,948 expires 10/7/2034 - Methods for treating eosinophilic esophagitis by administering an IL-4R inhibitor
9,290,574 expires 10/7/2034 - Methods for treating eosinophilic esophagitis by administering an IL-4R inhibitor
10,059,771 expires 20/6/2034 - Methods for treating nasal polyposis by administering an IL-4R antagonist
8,945,559 expires 17/10/2032 - Stabilized formulations containing anti-interleukin-4 receptor (IL-4R) antibodies
Evkeeza
400 30
350
25
300
20
250
200 15
150
10
11 11 11 11
100 10
9
8
7 7 5
50 6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Evkeeza Median
Description
Evinacumab-dgnb is an angiopoietin-like protein 3 (ANGPTL3) inhibitor monoclonal antibody (IgG4 isotype) produced by recom-
binant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Evinacumab-dgnb has an approximate molecular
weight of 146 kDa.
Indications
Evkeeza is indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of adult
and pediatric patients, aged 12 years and older, with homozygous familial hypercholesterolemia (HoFH).

Key Patent
Number: 10,358,487
Eylea
12,000 30
10,000 25
8,000 20
6,000 15
15
14 14 14 14
4,000 12 10
11
9
8
2,000 7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Eylea Median
Description
Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to
the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glyco-
protein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the
total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary
(CHO) cells.
Indications
Eylea is indicated for the treatment of:
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
Macular Edema Following Retinal Vein Occlusion (RVO)
Diabetic Macular Edema (DME)
Diabetic Retinopathy (DR)

Key Patent
Number: 7,070,959

10,973,879 expires 17/5/2039 - Use of a VEGF antagonist to treat angiogenic eye disorders
10,406,226 expires 22/3/2026 - Method of manufacturing VEGF antagonist fusion proteins
10,857,231 expires 22/3/2026 - Formulations of VEG antagonist fusion proteins and method of manufacturing them
Libtayo
3,000 30
2,500 25
2,000 20
1,500 15
15
14 14 14 14
1,000 10
11
10
8
500 7 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Libtayo Median
Description
Cemiplimab-rwlc is a human programmed death receptor-1 (PD-1) blocking antibody. Cemiplimab-rwlc is a recombinant human
IgG4 monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2. Cemiplimab-rwlc is produced by
recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Cemiplimab-rwlc has an approximate molec-
ular weight of 146 kDa.
Indications
Libtayo is a programmed death receptor-1 (PD-1) blocking antibody indicated:
Cutaneous Squamous Cell Carcinoma (CSCC) for the treatment of patients with metastatic cutaneous squamous cell carcinoma
(mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.
Basal Cell Carcinoma (BCC):
for the treatment of patients with locally advanced BCC (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a
hedgehog pathway inhibitor is not appropriate.
for the treatment of patients with metastatic BCC (mBCC) previously treated with a hedgehog pathway inhibitor or for whom a
hedgehog pathway inhibitor is not appropriate.
Non-Small Cell Lung Cancer (NSCLC) for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression
[Tumor Proportion Score (TPS) = 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations, and is:
locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic.

Key Patent
Number: 9,987,500
Roche
Actemra
8,000 30
7,000 28 28 28 28 28
25
6,000 24
22 20
5,000
18 18
4,000 15
3,000 14
10
2,000
5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Actemra Median
Description
Tocilizumab is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin
IgG1κ (γ 1, κ) subclass with a typical H 2 L 2 polypeptide structure. Each light chain and heavy chain consists of 214 and 448 amino
acids, respectively. The four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds. Actemra has a molecular
weight of approximately 148 kDa. The antibody is produced in mammalian (Chinese hamster ovary) cells.
Indications
Actemra (tocilizumab) is indicated for treatment of:
Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Dis-
ease-Modifying Anti-Rheumatic Drugs (DMARDs).
Adult patients with giant cell arteritis.
Slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-
ILD)
Patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis.
Patients 2 years of age and older with active systemic juvenile idiopathic arthritis.
Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening
cytokine release syndrome.

Key Patent
Number: 5,795,965

10,774,148 expires 26/2/2036 - Composition for treating IL-6-related diseases
9,969,800 expires 4/2/2036 - IL-8 antibodies
10,738,111 expires 18/12/2035 - Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use
10,253,100 expires 17/7/2035 - Therapeutic antigen-binding molecule with a FcRn-binding domain that promotes antigen clearance
10,761,091 expires 1/7/2034 - Interference-suppressed immunoassay to detect anti-drug antibodies in serum samples

10,618,965 expires 9/2/2033 - Method for altering plasma retention and immunogenicity of antigen-binding molecule
9,657,090 expires 11/12/2032 - Method of treating alveolar bone loss through the use of anti-sclerostin antibodies
9,409,990 expires 9/11/2032 - Methods of inhibiting tumor growth by antagonizing IL-6 receptor
10,927,435 expires 10/10/2032 - Compositions for the treatment of rheumatoid arthritis and methods of using same
10,538,584 expires 2/8/2032 - Methods for treating bone gap defects
10,450,381 expires 17/11/2031 - Methods of treatment that include the administration of bispecific antibodies
10,022,319 expires 5/9/2031 - Stabilized antibody-containing liquid formulations
9,228,017 expires 26/12/2030 - Antibody constant region variant
10,501,769 expires 25/10/2030 - Method for the production of a glycosylated immunoglobulin
8,568,720 expires 5/11/2029 - High concentration antibody-containing liquid formulation
10,662,245 expires 25/9/2029 - Methods of reducing IL-6 activity for disease treatment
8,562,991 expires 25/9/2029 - Antibody molecules that bind to IL-6 receptor
10,011,858 expires 26/6/2029 - Methods for producing polypeptides by regulating polypeptide association
10,717,781 expires 5/6/2029 - Neuroinvasion inhibitor
10,472,623 expires 10/4/2029 - Antigen-binding molecule capable of binding two or more antigen molecules repeatedly
9,688,762 expires 21/3/2029 - Modified antibody constant region
8,771,686 expires 22/11/2028 - Methods for treating a disease involving choroidal neovascularization by administering an IL-6 recep-
tor antibody
9,089,553 expires 14/11/2028 - Method for inhibiting bone resorption
9,683,027 expires 14/10/2028 - Method for production of antibody
10,273,293 expires 18/9/2028 - Method for inhibiting bone resorption
10,934,344 expires 30/3/2028 - Methods of modifying antibodies for purification of bispecific antibodies
9,296,812 expires 25/1/2028 - Sclerostin binding antibodies
8,945,558 expires 2/11/2027 - Methods for treating myocardial infarction comprising administering an IL-6 inhibitor
10,562,964 expires 13/8/2027 - Methods for isolating antibodies that bind sclerostin
10,584,173 expires 1/6/2027 - Nucleic acids encoding high affinity antibodies to human IL-6 receptor
8,080,248 expires 1/6/2027 - Method of treating rheumatoid arthritis with an IL-6R antibody
8,192,741 expires 1/6/2027 - Method of treating rheumatoid arthritis with an anti-IL-6R antibody
8,568,721 expires 1/6/2027 - Method of treating rheumatoid arthritis with an anti-IL-6R antibody
9,884,916 expires 1/6/2027 - High affinity antibodies to human IL-6 receptor
9,670,269 expires 30/3/2027 - Methods of modifying antibodies for purification of bispecific antibodies
8,715,663 expires 1/1/2027 - Epitopes
8,398,980 expires 27/9/2026 - Subtypes of humanized antibody against interleukin-6 receptor
8,637,643 expires 25/4/2026 - Sclerostin binding antibody

9,353,174 expires 25/4/2026 - Epitopes
9,902,777 expires 28/5/2025 - Methods for producing subtypes of humanized antibody against interleukin-6 receptor
8,734,800 expires 24/3/2025 - Subtypes of humanized antibody against interleukin-6 receptor
8,709,409 expires 22/6/2024 - Method for treating rheumatoid arthritis by administering an anti-IL-6 antibody and methotrexate
9,657,095 expires 16/6/2024 - Antibodies specific for sclerostin and methods for increasing bone mineralization
10,744,201 expires 28/4/2024 - Method for treating rheumatoid arthritis with a human IL-6 receptor antibody and methotrexate
8,840,884 expires 14/2/2023 - Antibody-containing solution pharmaceuticals
9,051,384 expires 14/2/2023 - Antibody-containing solution formulations
9,255,145 expires 2/4/2022 - Therapeutic agent for chronic arthritides diseases of childhood-related diseases
9,017,677 expires 22/9/2021 - Methods of treating a disease mediated by sensitized T cells
8,173,126 expires 27/10/2020 - Blood VEGF level-lowering agent containing IL-6 antagonist as the active ingredient
8,986,685 expires 24/11/2019 - Compositions and methods for increasing bone mineralization
9,791,462 expires 24/11/2019 - Compositions and methods for increasing bone mineralization
Enspryng
1,400 30
1,200 25
1,000
20
800
15
600
13 13 13 13
12 10
400 11
10
8 8
200 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Enspryng Median
Description
Satralizumab-mwge is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody based on a hu-
man IgG2 framework. Each light chain and heavy chain consists of 214 and 443 amino acids, respectively. Satralizumab-mwge is a
glycoprotein with an approximate molecular weight of 143 kDa and is produced by recombinant DNA technology in Chinese hamster
ovary cells. The binding of satralizumab-mwge to the IL-6 receptor is pH-sensitive.
Indications
Enspryng is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquapor-
in-4 (AQP4) antibody positive.

Key Patent
Number: 8,562,991


10,774,148 expires 26/2/2036 - Composition for treating IL-6-related diseases
9,969,800 expires 4/2/2036 - IL-8 antibodies
10,738,111 expires 18/12/2035 - Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use
Gazyva
2,000 30
1,800
25
1,600
1,400
20
1,200
1,000 15
800 14 14 14 14 14
12 10
600 11
9 9
400
7 5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Gazyva Median
Description
Obinutuzumab is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass. It recognizes a specific epitope of the CD20
molecule found on B cells. The molecular mass of the antibody is approximately 150 kDa. Gazyva (obinutuzumab) injection is
produced by mammalian cell (CHO) suspension culture. Gazyva was engineered for reduced fucose content as compared to a typical
IgG1 produced in CHO cells.
Indications
Gazyva (obinutuzumab) is a CD20-directed cytolytic antibody indicated:
in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia.
in combination with bendamustine followed by Gazyva monotherapy, for the treatment of patients with follicular lymphoma who
relapsed after, or are refractory to, a rituximab-containing regimen.
in combination with chemotherapy followed by Gazyva monotherapy in patients achieving at least a partial remission, for the treat-
ment of adult patients with previously untreated stage II bulky, III or IV follicular lymphoma.

Key Patent
Number: 6,602,684

10,525,137 expires 28/12/2036 - Formulations with reduced degradation of polysorbate

9,597,411 expires 30/4/2033 - Anti-PMEL17 antibodies and immunoconjugates
10,556,949 expires 18/10/2032 - Antigen-binding molecule inducing immune response to target antigen
9,447,159 expires 26/4/2032 - Immunoconjugates
10,611,825 expires 19/3/2032 - Monovalent antigen binding proteins
10,793,621 expires 27/2/2032 - Nucleic acid encoding dual Fc antigen binding proteins
9,982,036 expires 27/2/2032 - Dual FC antigen binding proteins
9,683,047 expires 16/9/2029 - Methods for treating progressive multiple sclerosis
10,450,379 expires 14/11/2026 - Method for treating joint damage
8,067,232 expires 19/9/2022 - Antibody composition-producing cell with inactivated A-1,6-fucosyltransferase
7,741,442 expires 2/7/2022 - Antibody composition exhibiting increased cellular cytotoxicity due to glycosylation
8,039,595 expires 26/11/2021 - Glycoengineered, recombinant antibody to CCR-4 with reduced fucosylation
Hemlibra
9,000 30
8,000
25
7,000
6,000 20
5,000
15
4,000
14 14 14 14 14
3,000 12 10
11
2,000 9 9
7 5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Hemlibra Median
Description
Emicizumab-kxwh is a humanized monoclonal modified immunoglobulin G4 (IgG4) bispecific antibody binding factor IXa and fac-
tor X. Emicizumab-kxwh has an approximate molecular weight of 145.6 kDa and is produced in genetically engineered mammalian
(Chinese hamster ovary) cells. Emicizumab-kxwh has no structural relationship or sequence homology to FVIII and, as such, does not
induce or enhance the development of direct inhibitors to FVIII.
Indications
Hemlibra is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients
ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors.

Key Patent
Number: 9,334,331

10,759,870 expires 27/9/2038 - Multispecific antigen-binding molecules having blood coagulation factor VIII (FVIII) cofactor func-
tion-substituting activity and pharmaceutical formulations containing such a molecule as an active ingredient
Kadcyla
4,000 30
3,500
25
3,000
20
2,500
2,000 15
1,500 14 14 14 14 14
12 10
11
1,000 9 9
7 5
500
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Kadcyla Median
Description
Kadcyla (ado-trastuzumab emtansine) is a HER2-targeted antibody-drug conjugate (ADC) which contains the humanized anti-HER2
IgG1, trastuzumab, covalently linked to the microtubule inhibitory drug DM1 (a maytansine derivative) via the stable thioether linker
MCC (4-[N-maleimidomethyl] cyclohexane-1-carboxylate). Emtansine refers to the MCC-DM1 complex. The antibody trastuzumab,
is a well characterized recombinant monoclonal antibody product produced by mammalian (Chinese hamster ovary) cells, and the
small molecule components (DM1 and MCC) are produced by chemical synthesis. Ado-trastuzumab emtansine contains an average
of 3.5 DM1 molecules per antibody.
Indications
Kadcyla is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for:
the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately
or in combination. Patients should have either: received prior therapy for metastatic disease, or developed disease recurrence during
or within six months of completing adjuvant therapy.
the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane
and trastuzumab-based treatment. (

Key Patent
Number: 7,097,840


10,849,849 expires 4/8/2038 - Subcutaneous HER2 antibody formulations
10,898,570 expires 6/7/2036 - Combination therapy with an anti-HER2 antibody-drug conjugate and a Bcl-2 inhibitor
10,077,318 expires 12/2/2036 - Cysteine engineered antibodies and conjugates
8,652,474 expires 6/8/2031 - Composition comprising antibody that binds to domain II of HER2 and acidic variants thereof
8,937,161 expires 9/1/2031 - Cysteine engineered anti-TENB2 antibodies and antibody drug conjugates
8,663,643 expires 22/12/2030 - Combinations of an anti-HER2 antibody-drug conjugate and chemotherapeutic agents, and methods
of use
10,494,432 expires 26/8/2030 - Anti-CD79B antibodies and immunoconjugates and methods of use
8,163,287 expires 7/12/2029 - Combination therapy of her expressing tumors
10,689,457 expires 15/6/2029 - Treatment of metastatic breast cancer
Lucentis
1,800 30
1,600
25
1,400
1,200 20
1,000
15
800
14 14 14 14 14
600 12 10
11
400 9 9
7 5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Lucentis Median
Description
Lucentis (ranibizumab injection) is a recombinant humanized IgG1κ isotype monoclonal antibody fragment designed for intraocular
use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). Ranibizumab,
which lacks an Fc region, has a molecular weight of approximately 48 kilodaltons and is produced by an E. coli expression system in a
nutrient medium containing the antibiotic tetracycline.
Indications
Lucentis is indicated for the treatment of patients with:
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
Macular Edema Following Retinal Vein Occlusion (RVO)
Diabetic Macular Edema (DME)
Diabetic Retinopathy (DR)
Myopic Choroidal Neovascularization (mCNV)

Key Patent
Number: 6,407,213

10,898,570 expires 6/7/2036 - Combination therapy with an anti-HER2 antibody-drug conjugate and a Bcl-2 inhibitor
10,017,577 expires 14/6/2036 - Antibodies and immunoconjugates
10,335,485 expires 15/4/2031 - Anti-VLA-4 antibodies
9,533,044 expires 23/2/2030 - Methods of treating inflammatory disorders using high concentration natalizumab compositions
9,090,684 expires 17/11/2029 - Stable and soluble antibodies inhibiting VEGF
8,288,352 expires 17/3/2029 - Auristatins having an aminobenzoic acid unit at the N terminus
9,556,266 expires 30/11/2027 - Methods of treating sickle cell disease with anti-P-selectin antibodies
7,964,566 expires 26/11/2026 - Monomethylvaline compounds capable of conjugation to ligands
7,659,241 expires 15/7/2026 - Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease
9,522,194 expires 7/7/2026 - Methods of using monomethylvaline compositions having phenylalanine carboxy modifications at the
C-terminus
8,597,654 expires 6/4/2026 - Adjuvant therapy with an anti-ERBB2 antibody conjugated to a maytansiniod
8,691,232 expires 21/2/2026 - Extending time to disease progression or survival in cancer patients
8,404,234 expires 7/12/2025 - Fixed dosing of HER antibodies
9,017,671 expires 19/10/2025 - Method of treating cancer with a pharmaceutical formulation comprising a HER2 antibody
8,241,630 expires 19/8/2025 - HER2 antibody composition
7,892,549 expires 11/12/2023 - Treatment with anti-ErbB2 antibodies
8,076,066 expires 18/5/2021 - Gene detection assay for improving the likelihood of an effective response to a HER2 antibody cancer
therapy
8,440,402 expires 18/5/2021 - Gene detection assay for improving the likelihood of an effective response to a HER2 antibody cancer
therapy
Mircera
700 30
600 25
500
20
400
15
300
13 13 13 13 13
10
200 11
10
8 8
100 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Mircera Median
Description
Methoxy polyethylene glycol-epoetin beta, is an ESA which differs from erythropoietin through formation of a chemical bond
between either the N-terminal amino group or the ε-amino group of any lysine present in erythropoietin, predominantly Lys 52 and
Lys 45 , and methoxy polyethylene glycol (PEG) butanoic acid (approximately 30,000 daltons). This results in a total molecular weight
of approximately 60,000 daltons. Methoxy polyethylene glycol-epoetin beta is produced in Chinese hamster ovary (CHO) cells using
recombinant DNA technology.
Indications
Mircera is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia associated with chronic kidney disease
(CKD) in:
adult patients on dialysis and adult patients not on dialysis.
pediatric patients 5 to 17 years of age on hemodialysis who are converting from another ESA after their hemoglobin level was stabi-
lized with an ESA

Key Patent
Number: 6,583,272

10,273,277 expires 14/9/2031 - Method for purifying PEGylated erythropoietin
8,795,533 expires 24/2/2031 - Chromatographic methods
8,138,317 expires 17/10/2029 - Purification of pegylated polypeptides

8,889,837 expires 7/12/2028 - Purification of pegylated polypeptides
7,459,429 expires 16/12/2024 - Method of treating disturbances of iron distribution in inflammatory intestinal diseases
7,459,435 expires 21/7/2024 - Treatment of disturbances of iron distribution
7,459,436 expires 27/5/2024 - Treatment of disturbances of iron distribution
7,128,913 expires 6/4/2023 - Erythropoietin conjugates
Ocrevus
12,000 30
10,000 25
8,000 20
6,000 15
14 14 14 14 14
4,000 12 10
11
9 9
2,000 7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Ocrevus Median
Description
Ocrelizumab is a recombinant humanized monoclonal antibody directed against CD20-expressing B-cells. Ocrelizumab is a glyco-
sylated immunoglobulin G1 (IgG1) with a molecular mass of approximately 145 kDa.
Indications
Ocrevus is indicated for the treatment of:
Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary
progressive disease.
In adults Primary progressive MS

Key Patent
Number: 7,799,900

Perjeta
8,000 30
7,000
25
6,000
20
5,000
4,000 15
3,000 14 14 14 14 14
12 10
11
2,000 9 9
7 5
1,000
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Perjeta Median
Description
Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of
the human epidermal growth factor receptor 2 protein (HER2). Pertuzumab is produced by recombinant DNA technology in a mam-
malian cell (Chinese Hamster Ovary) culture. Pertuzumab has an approximate molecular weight of 148 kDa.
Indications
Perjeta is a HER2/neu receptor antagonist indicated for:
Use in combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC)
who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
Use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced,
inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment
regimen for early breast cancer.
adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence

Key Patent
Number: 7,862,817

Phesgo
1,800 30
1,600
25
1,400
1,200 20
1,000
15
800
600 10
400 8 8 8 8 8
5
200 6
5
4 4 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Phesgo Median
Description
Phesgo is a combination of pertuzumab, trastuzumab, and hyaluronidase. Pertuzumab is a recombinant humanized monoclonal
antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein
(HER2). Pertuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Pertu-
zumab has an approximate molecular weight of 148 kDa. Trastuzumab is a humanized IgG1κ monoclonal antibody that selectively
binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab
is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Trastuzumab has a molecular
weight of approximately 148 kDa. Hyaluronidase (recombinant human) is an endoglycosidase used to increase the dispersion and
absorption of co-administered drugs when administered subcutaneously. It is a glycosylated single-chain protein produced by mam-
malian (Chinese Hamster Ovary) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20).
Hyaluronidase (recombinant human) has a molecular weight of approximately 61 kDa.
Indications
Phesgo is a combination of pertuzumab and trastuzumab, HER2/neu receptor antagonists, and hyaluronidase, an endoglycosidase,
indicated for:
Use in combination with chemotherapy as:
neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater
than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.
adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence
Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not re-
ceived prior anti-HER2 therapy or chemotherapy for metastatic disease.

Key Patent
Number: 7,767,429


Polivy
3,000 30
2,500 25
2,000 20
1,500 15
14 14 14 14 14
1,000 12 10
11
9 9
500 7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Polivy Median
Description
Polatuzumab vedotin-piiq is a CD79b-directed antibody-drug conjugate (ADC) consisting of three components: 1) the humanized
immunoglobulin G1 (IgG1) monoclonal antibody specific for human CD79b; 2) the small molecule anti-mitotic agent MMAE; and
3) a protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB) that covalently attaches
MMAE to the polatuzumab antibody. Polatuzumab vedotin-piiq has an approximate molecular weight of 150 kDa. An average of 3.5
molecules of MMAE are attached to each antibody molecule. Polatuzumab vedotin-piiq is produced by chemical conjugation of the
antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small
molecule components are produced by chemical synthesis.
Indications
Polivy in combination with bendamustine and a rituximab product is indicated for the treatment of adult patients with relapsed or
refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies.

Key Patent
Number: 8,088,378
Rituxan Hycela
3,000 30
2,500 25
2,000 20
1,500 15
13 13 13 13 13
1,000 10
11
10
8 8
500 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Rituxan Median
Description
Rituxan HYCELA is a combination of rituximab and hyaluronidase human. Rituximab is a genetically engineered chimeric murine/
human monoclonal IgG1κ antibody directed against the CD20 antigen. Rituximab has an approximate molecular weight of 145 kD.
Rituximab has a binding affinity for the CD20 antigen of approximately 8.0 nM. Rituximab is produced by mammalian cell (Chinese
Hamster Ovary) suspension. Recombinant human hyaluronidase is an endoglycosidase used to increase the dispersion and absorption
of co-administered drugs when administered subcutaneously. It is produced by mammalian (Chinese Hamster Ovary) cells contain-
ing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). It is a glycosylated single-chain protein with an
approximate molecular weight of 61 kD.
Indications
Rituxan HYCELA is a combination of rituximab, a CD20-directed cytolytic antibody, and hyaluronidase human, an endoglycosidase,
indicated for the treatment of adult patients with:
Relapsed or refractory, follicular lymphoma as a single agent Previously untreated follicular lymphoma in combination with first line
chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as sin-
gle-agent maintenance therapy
Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and
prednisone (CVP) chemotherapy
Previously untreated diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, prednisone
(CHOP) or other anthracycline-based chemotherapy regimens
Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide (FC)

Key Patent
Number: 7,767,429

Tecentriq
14,000 30
12,000 25
10,000
20
8,000
15
6,000
14 14 14 14 14
12 10
4,000 11
9 9
2,000 7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Tecentriq Median
Description
Atezolizumab is a programmed cell death ligand 1 (PD-L1) blocking antibody. Atezolizumab is an Fc-engineered, humanized,
non-glycosylated IgG1κ immunoglobulin that has a calculated molecular mass of 145 kDa.
Indications
Tecentriq is a programmed death-ligand 1 (PD-L1) blocking antibody indicated:
for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who: are not eligible for cisplatin-contain-
ing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering = 5% of the tumor
area), as determined by an FDA-approved test, or are not eligible for any platinum-containing chemotherapy regardless of PD-L1
status. This indication is approved under accelerated approval based on tumor response rate and duration of response.
for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained = 50%
of tumor cells [TC = 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering = 10% of the tumor area [IC = 10%] ), as
determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult patients with metastatic non-squa-
mous NSCLC with no EGFR or ALK genomic tumor aberrations.
in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squa-
mous NSCLC with no EGFR or ALK genomic tumor aberrations.
for the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing
chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for
NSCLC harboring these aberrations prior to receiving Tecentriq.
Triple-Negative Breast Cancer (TNBC) in combination with paclitaxel protein-bound for the treatment of adult patients with unre-
sectable locally advanced or metastatic TNBC whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of
any intensity covering = 1% of the tumor area), as determined by an FDA approved test. This indication is approved under accelerated
approval based on progression free survival. Continued approval for this indication may be contingent upon verification and descrip-
tion of clinical benefit in a confirmatory trial(s).
Small Cell Lung Cancer (SCLC) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with
extensive-stage small cell lung cancer (ES-SCLC).
Hepatocellular Carcinoma (HCC) in combination with bevacizumab for the treatment of patients with unresectable or metastatic
HCC who have not received prior systemic therapy.
Melanoma in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unre-
sectable or metastatic melanoma.

Key Patent
Number: 8,217,149

10,875,922 expires 17/6/2035 - Anti-PDL1 antibody formulations

Tnkase
2,000 30
1,800
25
1,600
1,400
20
1,200
1,000 15
800
13 13 13 13 13
10
600 11
10
400 8 8
7 5
200
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Activase Median
Description
TNKase (Tenecteplase) is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established
mammalian cell line (Chinese Hamster Ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the
following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparag-
ine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino
acids 296-299 in the protease domain. TNKase is a sterile, white to off-white, lyophilized powder for single intravenous (IV) bolus
administration after reconstitution with Sterile Water for Injection (SWFI), USP. Each vial of TNKase nominally contains 52.5 mg
Tenecteplase, 0.55 g L-arginine, 0.17 g phosphoric acid, and 4.3 mg polysorbate 20, which includes a 5% overfill. Each vial will deliver
50 mg of Tenecteplase.
Indications
TNKase (Tenecteplase) is indicated for use in the reduction of mortality associated with acute myocardial infarction (AMI). Treat-
ment should be initiated as soon as possible after the onset of AMI symptoms (see CLINICAL STUDIES ).

Key Patent
Number: 5,385,732

8,916,148 expires 26/9/2030 - Tissue plasminogen activator variant uses
Xolair
Description
Omalizumab is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human immunoglobu-
lin E (IgE). The antibody has a molecular weight of approximately 149 kiloDaltons. Xolair is produced by a Chinese hamster ovary cell
suspension culture.
Indications
Xolair is an anti-IgE antibody indicated for:
Moderate to severe persistent asthma in adults and pediatric patients 6 years of age and older with a positive skin test or in vitro reac-
tivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids
Nasal polyps in adult patients 18 years of age and older with inadequate response to nasal corticosteroids, as add-on maintenance
treatment
Chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine
treatment

Key Patent
Number: 6,267,958

10,689,438 expires 29/6/2036 - Stable protein solution formulation containing high concentration of an anti-VEGF antibody
10,017,732 expires 25/12/2034 - Cell culture compositions with antioxidants and methods for polypeptide production
9,597,411 expires 30/4/2033 - Anti-PMEL17 antibodies and immunoconjugates
8,969,526 expires 24/4/2032 - Antibody Fc variants
10,611,825 expires 19/3/2032 - Monovalent antigen binding proteins
10,793,621 expires 27/2/2032 - Nucleic acid encoding dual Fc antigen binding proteins

7,705,132 expires 1/11/2027 - Stable polypeptide formulations
8,597,654 expires 6/4/2026 - Adjuvant therapy with an anti-ERBB2 antibody conjugated to a maytansiniod
8,691,232 expires 21/2/2026 - Extending time to disease progression or survival in cancer patients
10,034,940 expires 4/11/2025 - High concentration antibody and protein formulations
8,562,992 expires 19/9/2025 - Immunoglobulin variants and uses thereof
7,700,722 expires 12/5/2025 - Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing
8,961,964 expires 29/3/2024 - High concentration antibody and protein formulations
8,835,611 expires 2/5/2023 - Calicheamicin derivative-carrier conjugates
8,840,884 expires 14/2/2023 - Antibody-containing solution pharmaceuticals
9,051,384 expires 14/2/2023 - Antibody-containing solution formulations
6,875,432 expires 21/5/2022 - Reduced-viscosity concentrated protein formulations
7,666,413 expires 18/10/2021 - Method of reducing viscosity of high concentration protein formulations
7,531,645 expires 3/5/2019 - Protein purification
6,761,889 expires 23/8/2017 - Anti-IgE antibodies
Sanofi
Adlyxin
Description
Adlyxin contains lixisenatide, which acts as a GLP-1 receptor agonist. Lixisenatide is a peptide containing 44 amino acids, which is
amidated at the C-terminal amino acid (position 44). The order of the amino acids is given in the figure below.
Indications
Adlyxin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Key Patent
Number:
Apidra
500 30
450
25
400
350
20
300
250 15
200
10
150
100
7 7 7 7 7 7 5
6
50
4 4 3
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Apidra Median
Description
Apidra (insulin glulisine injection) is a rapid-acting human insulin analog used to lower blood glucose. Insulin glulisine is produced
by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Insulin glulisine differs from
human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glu-
tamic acid. Chemically, insulin glulisine is 3 B -lysine-29 B -glutamic acid-human insulin, has the empirical formula C 25 8 H 38 4 N
6 4 O 7 8 S 6 and a molecular weight of 5823 and has the following structural formula: Apidra (insulin glulisine injection) is a sterile,
aqueous, clear, and colorless solution for subcutaneous or intravenous use. Each milliliter of Apidra contains 100 units (3.49 mg) insu-
lin glulisine, 3.15 mg metacresol, 6 mg tromethamine, 5 mg sodium chloride, 0.01 mg polysorbate 20, and water for injection. Apidra
has a pH of approximately 7.3. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and/or sodium hydroxide.
Chemical Structure
Indications
Apidra is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

Key Patent
Number: 6,960,561

Cablivi
1,200 30
1,000 25
800 20
600 15
400 12 12 12 12 12 12 10
10
8 8
200 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Cablivi Median
Description
Caplacizumab-yhdp is a von Willebrand factor (vWF)-directed antibody fragment that consists of two identical humanized building
blocks, linked by a three-alanine linker. Caplacizumab-yhdp is produced in Escherichia coli by recombinant DNA technology and has
an approximate molecular weight of 28 kDa.
Indications
Cablivi is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination
with plasma exchange and immunosuppressive therapy.

Key Patent
Number: 7,807,162

10,858,445 expires 7/11/2036 - Methods of treating TTP with immunoglobulin single variable domains and uses thereof
10,919,980 expires 7/4/2036 - Methods of treating TTP with immunoglobulin single variable domains and uses thereof
Elitek
Description
Elitek (rasburicase) is a recombinant urate-oxidase produced by a genetically modified Saccharomyces cerevisiae strain. The cDNA
coding for rasburicase was cloned from a strain of Aspergillus flavus. Rasburicase is a tetrameric protein with identical subunits. Each
subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa.
Indications
Elitek is indicated for the initial management of plasma uric acid levels in pediatric and adult patients with leukemia, lymphoma, and
solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma
uric acid.

Key Patent
Number: 5,382,518

9,534,013 expires 10/9/2027 - Purification of proteins with cationic surfactant
8,148,123 expires 8/9/2027 - Methods for lowering elevated uric acid levels using intravenous injections of PEG-uricase
7,927,589 expires 14/12/2020 - PEG-urate oxidase conjugates and use thereof
7,927,852 expires 27/9/2020 - Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates
8,921,064 expires 29/11/2019 - Method for purifying urate oxidase tetramers and octamers
Fabrazyme
1,400 30
1,200 25
1,000
20
800
15
600
12 12 12 12 12 12 10
400 10
8 8
200 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Fabrazyme Median
Description
Agalsidase beta is a recombinant human a-galactosidase A enzyme with the same amino acid sequence as the native enzyme. Purified
agalsidase beta is a homodimeric glycoprotein with a molecular weight of approximately 100 kD. The mature protein is comprised of
two subunits of 398 amino acids (approximately 51 kD), each of which contains three N-linked glycosylation sites. The enzyme a-ga-
lactosidase A catalyzes the hydrolysis of GL-3 and other a-galactyl-terminated neutral glycosphingolipids, such as galabiosylceramide
and blood group B substances to ceramide dihexoside and galactose.
Indications
Fabrazyme is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.

Key Patent
Number: 5,356,804

6,905,856 expires 21/12/2021 - Soluble GlcNAc phosphotransferase
6,642,038 expires 5/7/2021 - GlcNAc phosphotransferase of the lysosomal targeting pathway
6,770,468 expires 26/6/2021 - Phosphodiester-a-GlcNAcase of the lysosomal targeting pathway
7,067,127 expires 28/1/2021 - GIcNAc phosphotransferase of the lysosomal targeting pathway
6,861,242 expires 11/11/2020 - Methods for producing highly phosphorylated lysosomal hydrolases
7,351,410 expires 29/10/2020 - Treatment of Pompe's disease

6,537,785 expires 10/8/2020 - Methods of treating lysosomal storage diseases
6,828,135 expires 10/8/2020 - Phosphodiester alpha-GlcNAcase of the lysosomal targeting pathway
7,371,366 expires 10/8/2020 - GlcNAc phosphotransferase of the lysosomal targeting pathway
Kevzara
1,400 30
1,200 25
1,000
20
800
15
600 15 15
14 14 14
12 12 10
400
9 9
200 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Kevzara Median
Description
Sarilumab is a human recombinant monoclonal antibody of the IgG1 subclass that binds to the IL-6 receptor and has an approximate
molecular weight of 150 kDa. Sarilumab is produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension
culture.
Indications
Kevzara is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an
inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

Key Patent
Number: 7,582,298

10,718,754 expires 1/2/2039 - System and method for characterizing protein dimerization
10,137,193 expires 5/2/2036 - Methods for treating or preventing asthma by administering an IL-4R antagonist
10,066,017 expires 21/1/2036 - Methods for treating chronic sinusitis with nasal polyps by administering an IL-4R antagonist
10,059,771 expires 20/6/2034 - Methods for treating nasal polyposis by administering an IL-4R antagonist
9,943,594 expires 28/7/2033 - Methods for the treatment of rheumatoid arthritis
9,409,990 expires 9/11/2032 - Methods of inhibiting tumor growth by antagonizing IL-6 receptor
10,433,528 expires 29/10/2032 - Humanized IL-6 and IL-6 receptor

10,927,435 expires 10/10/2032 - Compositions for the treatment of rheumatoid arthritis and methods of using same
Lemtrada
120 30
100 25
80 20
60 15
40 12 12 12 12 12 12 10
10
8 8
20 5
6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Lemtrada Median
Description
Alemtuzumab, a CD52-directed cytolytic antibody, is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H).
CAMPATH-1H is an IgG1κ antibody with human variable framework and constant regions, and complementarity-determining
regions from a murine (rat) monoclonal antibody (CAMPATH-1G). The CAMPATH-1H antibody has an approximate molecular
weight of 150 kD. CAMPATH is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing
neomycin.
Indications
Campath is a CD52-directed cytolytic antibody indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia
(B-CLL).

Key Patent
Number: 6,120,766

10,648,986 expires 17/3/2028 - Method of identifying risk for thyroid disorder
9,664,688 expires 15/2/2028 - Method of identifying risk for thyroid disorder
Lumizyme
3,000 30
2,500 25
24 24 24 24 24 24
2,000 20
20
1,500 15
16 16
1,000 12 10
500 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Myozyme Median
Description
Alglucosidase alfa is a hydrolytic lysosomal glycogen-specific enzyme encoded by the predominant of nine observed haplotypes of
the human acid a-glucosidase (GAA) gene. Alglucosidase alfa is produced by recombinant DNA technology in a Chinese hamster
ovary cell line. Alglucosidase alfa degrades glycogen by catalyzing the hydrolysis of a-1,4- and a-1,6- glycosidic linkages of lysosomal
glycogen. Alglucosidase alfa is a glycoprotein with a calculated mass of 99,377 Daltons for the polypeptide chain, and a total mass of
approximately 109,000 Daltons, including carbohydrates.
Indications
Lumizyme (alglucosidase alfa) [see Description (11) ] is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with
Pompe disease (acid a-glucosidase [GAA] deficiency).

Key Patent
Number: 7,056,712
Myozyme
3,000 30
2,500 25
24 24 24 24 24 24
2,000 20
20
1,500 15
16 16
1,000 12 10
500 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Myozyme Median
Description
Myozyme (alglucosidase alfa), a lysosomal glycogen-specific enzyme, consists of the human enzyme acid a-glucosidase (GAA),
encoded by the most predominant of nine observed haplotypes of this gene. Myozyme is produced by recombinant DNA technology
in a Chinese hamster ovary cell line. The Myozyme manufacturing process differs from that for Lumizyme, resulting in differences in
some product attributes. Alglucosidase alfa degrades glycogen by catalyzing the hydrolysis of a-1,4- and a-1,6- glycosidic linkages of
lysosomal glycogen.
Indications
Myozyme (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA defi-
ciency). Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared
to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately
studied to assure safety and efficacy

Key Patent
Number: 6,118,045

8,835,614 expires 23/7/2030 - Oligosaccharide-protein conjugates
8,759,501 expires 4/11/2029 - Oligosaccharides comprising an aminooxy group and conjugates thereof
8,399,657 expires 2/3/2023 - Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins and its
application thereof
10,363,291 expires 17/1/2022 - Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins and
applications thereof
10,973,887 expires 17/1/2022 - Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins and its
application thereof
7,786,277 expires 17/1/2022 - Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins
8,841,427 expires 17/1/2022 - Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins and
applications thereof
9,687,531 expires 17/1/2022 - Methods for introducing mannose 6 phosphate and other oligosaccharides onto glycoproteins and appli-
cations thereof
Praluent
700 30
600 25
500
20
400
15
300 15
14 14 14 14
10
200 11 11
8 8
100 7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Praluent Median
Description
Alirocumab is a human monoclonal antibody (IgG1 isotype) that targets proprotein convertase subtilisin kexin type 9 (PCSK9). Aliro-
cumab is a PCSK9 inhibitor produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Aliro-
cumab consists of two disulfide-linked human heavy chains, each covalently linked through a disulfide bond to a human κ light chain.
A single N-linked glycosylation site is located in each heavy chain within the CH2 domain of the Fc constant region of the molecule.
The variable domains of the heavy and light chains combine to form the PCSK9 binding site within the antibody. Alirocumab has an
approximate molecular weight of 146 kDa.
Indications
Praluent is indicated:
To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovas-
cular disease .
As an adjunct to diet, alone or in combination with other low density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults
with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C.
As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce
LDL-C.

Key Patent
Number: 8,062,640
Sarclisa
1,600 30
1,400
25
1,200
20
1,000
800 15
600
10
400 9 9 9 9 9 9
7 5
200 6 6
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Sarclisa Median
Description
Isatuximab-irfc, a CD38-directed cytolytic antibody, is a chimeric immunoglobulin G1 (IgG1) monoclonal antibody (mAb). Isatuxi-
mab-irfc is produced from a mammalian cell line (Chinese hamster ovary, CHO) using a fed-batch production process. Isatuximab-ir-
fc is composed of two identical immunoglobulin κ light chains and two identical immunoglobulin γ heavy chains and has an overall
molecular weight of approximately 148 kDa.
Indications
Sarclisa is indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myelo-
ma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. in combination with carfilzomib
and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior
lines of therapy.

Key Patent
Number: 8,153,765

Soliqua 100/33
450 30
400
25
350
300 20
250
15
200
150 10
11 11 11 11 11 11
100 9
7 7 5
50 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Soliqua Median
Description
Soliqua 100/33 (insulin glargine and lixisenatide injection), for subcutaneous use, is a combination of a long-acting basal insulin
analog, insulin glargine, and a GLP-1 receptor agonist, lixisenatide. Each Soliqua 100/33 prefilled single-patient-use disposable pen
contains 300 units of insulin glargine and 100 mcg of lixisenatide in 3 mL of a clear, colorless to almost colorless, sterile, and aqueous
solution. Each mL of solution contains 100 units insulin glargine and 33 mcg lixisenatide.
Indications
Soliqua 100/33 is a combination of insulin glargine and lixisenatide and is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.

Key Patent
Number: 6,528,486

10,610,595 expires 8/1/2035 - Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives
9,895,423 expires 8/1/2035 - Stabilized pharmaceutical formulations of insulin aspart
10,092,513 expires 1/4/2034 - Treatment of diabetes mellitus by long-acting formulations of insulins
9,345,750 expires 18/5/2031 - Long-acting formulations of insulin

9,526,764 expires 9/10/2029 - Combination of an insulin and a GLP-1-agonist
8,048,854 expires 5/7/2027 - Amidated insulin glargine
7,939,293 expires 26/5/2027 - Method for producing carboxy-terminal-amidified peptides
7,544,657 expires 5/11/2023 - Stabilized Exendin-4 compounds
Toujeo Solostar
1,800 30
1,600
25
1,400
1,200 20
1,000
15
800
600 12 12 12 12 12 12 10
10
400 8 8
5
200 6
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Toujeo Median
Description
Toujeo (insulin glargine injection) is a long-acting insulin supplied as a sterile solution for subcutaneous injection containing 300
units/mL of insulin glargine. Insulin glargine is a human insulin analog produced by recombinant DNA technology utilizing a non-
pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that
the amino acid asparagine at position A21 is replaced by glycine and two arginines remain at the C-terminus of the B-chain.
Indications
Toujeo is indicated to improve glycemic control in adults and pediatric patients 6 years of age and older with diabetes mellitus.

Key Patent
Number: 9,345,750
Zaltrap
100 30
90
25
80
70
20
60
50 15
40
10
30
20
5
10
1 1 1 1 1 1 1 1 1 1
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Zaltrap Median
Description
Ziv-aflibercept is a vascular endothelial growth factor inhibitor. It is a recombinant fusion protein consisting of Vascular Endothelial
Growth Factor (VEGF)-binding portions from the extracellular domains of human VEGF Receptors 1 and 2 fused to the Fc portion
of the human IgG1. Ziv-aflibercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) K-1 mammali-
an expression system. Ziv-aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains
glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa.
Indications
Zaltrap, in combination with fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for the treatment of patients with metastatic
colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.

Key Patent
Number: 7,070,959

Seagen
Adcetris (Oncology)
6,000 30
30 30
5,000 29
4,000 28
28 28 28
3,000 27
2,000 26
26 26
1,000 25
0 24
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Adcetris Median
Description
Adcetris (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) consisting of three components: 1) the chimeric
IgG1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent MMAE, and 3) a protease-cleavable linker that
covalently attaches MMAE to cAC10. Brentuximab vedotin has an approximate molecular weight of 153 kDa. Approximately 4 mol-
ecules of MMAE are attached to each antibody molecule. Brentuximab vedotin is produced by chemical conjugation of the antibody
and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule
components are produced by chemical synthesis.
Indications
Adcetris is a CD30-directed antibody-drug conjugate indicated for treatment of adult patients with:
Previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarba-
zine
Classical Hodgkin lymphoma (cHL) at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation
(auto-HSCT) consolidation.
Classical Hodgkin lymphoma (cHL) after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regi-
mens in patients who are not auto-HSCT candidates
Previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas
(PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide,
doxorubicin, and prednisone
Systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen
Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior
systemic therapy

Key Patent
Number: 7,090,843

9,211,319 expires 25/7/2032 - Weekly dosing regimens for anti-CD30 VC-PAB-MMAE antibody drug-conjugates
10,478,469 expires 24/11/2030 - Weekly dosing regimens for anti-CD30 vc-PAB-MMAE antibody drug-conjugates
8,263,083 expires 31/3/2029 - Combination therapy with antibody-drug conjugates
8,257,706 expires 18/6/2028 - CD30 binding agents and uses thereof
Adcetris (Transplantation)
6,000 30
30 30
5,000 29
4,000 28
28 28 28
3,000 27
2,000 26
26 26
1,000 25
0 24
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Adcetris Median
Description
Adcetris (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) consisting of three components: 1) the chimeric
IgG1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent MMAE, and 3) a protease-cleavable linker that
covalently attaches MMAE to cAC10. Brentuximab vedotin has an approximate molecular weight of 153 kDa. Approximately 4 mol-
ecules of MMAE are attached to each antibody molecule. Brentuximab vedotin is produced by chemical conjugation of the antibody
and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule
components are produced by chemical synthesis.
Indications
Adcetris is a CD30-directed antibody-drug conjugate indicated for:
The treatment of patients with Hodgkin lymphoma after failure of
autologous stem cell transplant (ASCT) or after failure of at least two
prior multi-agent chemotherapy regimens in patients who are not
ASCT candidates.
The treatment of patients with systemic anaplastic large cell lymphoma
after failure of at least one prior multi-agent chemotherapy regimen.

Key Patent
Number: 7,829,531

10,201,615 expires 20/10/2031 - Synergistic effects between auristatin-based antibody drug conjugates and inhibitors of the PI3K-AKT
mTOR pathway
9,272,052 expires 20/10/2031 - Synergistic effects between auristatin-based antibody drug conjugates and inhibitors of the PI3K-AKT
mTOR pathway
9,078,931 expires 29/9/2031 - Antibody drug conjugates (ADC) that bind to 191P4D12 proteins
9,314,538 expires 29/9/2031 - Nucleic acid molecules encoding antibody drug conjugates (ADC) that bind to 191P4D12 proteins
8,609,105 expires 18/3/2030 - Auristatin drug linker conjugates
9,463,252 expires 6/9/2029 - Auristatin drug linker conjugates
8,288,352 expires 17/3/2029 - Auristatins having an aminobenzoic acid unit at the N terminus
8,067,546 expires 23/3/2028 - Humanized anti-CD70 binding agents and uses thereof
9,522,194 expires 7/7/2026 - Methods of using monomethylvaline compositions having phenylalanine carboxy modifications at the
C-terminus
Servier
Asparlas
Description
Calaspargase pegol-mknl contains an asparagine specific enzyme derived from Escherichia coli , as a conjugate of L-asparaginase
(L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate (SC) linker. The SC
linker is a chemically stable carbamate bond between the mPEG moiety and the lysine groups of L-asparaginase. L-asparaginase is a
tetrameric enzyme that is produced endogenously by E. coli and consists of identical 34.5 kDa subunits. Approximately 31 to 39 mole-
cules of SC-PEG are linked to L-asparaginase; the molecular weight of each SC-PEG molecule is about 5 kDa.
Indications
Asparlas is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of
acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years.

Key Patent
Number: 7,807,436
SOBI
Gamifant
7,000 30
6,000 25
5,000
20
4,000
15
3,000
10
2,000
1,000 5
4 4 3 2 2 2 1 0 0 0
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Gamifant Median
Description
Emapalumab-lzsg is an interferon gamma (IFNγ) blocking antibody. Emapalumab-lzsg is produced in Chinese Hamster Ovary cells
by recombinant DNA technology. Emapalumab-lzsg is an IgG1 immunoglobulin with a molecular weight of approximately 148 kDa.
Indications
Gamifant is indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohis-
tiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. G

Key Patent
Number: 7,700,098
Kepivance
Description
Kepivance (palifermin) is a truncated human KGF produced by recombinant DNA technology in E coli . Kepivance is a water soluble,
140 amino acid protein with a molecular weight of 16.3 kilodaltons. It differs from endogenous human KGF in that the first 23 N
terminal amino acids have been deleted to improve protein stability.
Indications
Kepivance is a mucocutaneous epithelial human growth factor indicated to decrease the incidence and duration of severe oral mu-
cositis in patients with hematologic malignancies receiving myelotoxic therapy in the setting of autologous hematopoietic stem cell
support.

Key Patent
Number: 5,677,278

8,304,387 expires 16/3/2026 - Therapeutic formulations of keratinocyte growth factor
Kineret
3,000 30
2,500 25
2,000 20
1,500 15
1,000 10
500 5
4 4 3 2 2 2 1 0 0 0
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Kineret Median
Description
Kineret (anakinra) is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). Kineret differs
from native human IL-1Ra in that it has the addition of a single methionine residue at its amino terminus. Kineret consists of 153
amino acids and has a molecular weight of 17.3 kilodaltons. It is produced by recombinant DNA technology using an E coli bacterial
expression system.
Indications
Kineret is an interleukin-1 receptor antagonist indicated for: Rheumatoid Arthritis (RA) Reduction in signs and symptoms and slow-
ing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who
have failed 1 or more disease modifying antirheumatic drugs (DMARDs)
Cryopyrin-Associated Periodic Syndromes (CAPS) Treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID)
Deficiency of Interleukin-1 Receptor Antagonist (DIRA) Treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA)
Active Rheumatoid Arthritis Kineret is indicated for the reduction in signs and symptoms and slowing the progression of structural
damage in moderately to severely active rheumatoid arthritis (RA), in patients 18 years of age or older who have failed 1 or more
disease modifying antirheumatic drugs (DMARDs).
Kineret can be used alone or in combination with DMARDs other than Tumor Necrosis Factor (TNF) blocking agents

Key Patent
Number: 5,075,222


proteins
proteins
proteins
10,907,186 expires 11/12/2034 - Overexpression of n-glycosylation pathway regulators to modulate glycosylation of recombinant
proteins
10,513,723 expires 9/12/2034 - Decreasing ornithine production to decrease high mannose glycoform content of recombinant proteins
7,928,074 expires 31/10/2024 - Combination therapy with co-stimulatory factors
7,364,736 expires 28/11/2023 - Antibodies to OPGL
7,087,224 expires 27/6/2023 - Method of treating anemia by administering IL-1ra
7,867,481 expires 3/1/2023 - Method of treating anemia by administering IL-1ra
6,858,409 expires 22/2/2022 - Nucleic acids encoding interleukin-1 inhibitors and processes for preparing interleukin-1 inhibitors
7,186,810 expires 7/5/2021 - Modified peptides as therapeutic agents
7,723,490 expires 26/3/2021 - Process for correction of a disulfide misfold in Fc molecules
6,808,902 expires 9/11/2020 - Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules
6,552,170 expires 22/4/2020 - PEGylation reagents and compounds formed therewith
6,420,339 expires 14/10/2018 - Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility
6,770,746 expires 5/10/2017 - Chemical modification of proteins to improve biocompatibility and bioactivity
Spectrum
Zevalin
Description
Zevalin (ibritumomab tiuxetan) is the immunoconjugate resulting from a stable thiourea covalent bond between the monoclonal anti-
body ibritumomab and the linker-chelator tiuxetan [N-[2-bis(carboxymethyl)amino]-3-(p-isothiocyanatophenyl)-propyl]-[N-[2-bis(-
carboxymethyl)amino]-2-(methyl)-ethyl]glycine. This linker-chelator provides a high affinity, conformationally restricted chelation
site for Yttrium-90. The approximate molecular weight of ibritumomab tiuxetan is 148 kD. The antibody moiety of Zevalin is ibritu-
momab, a murine IgG 1κ monoclonal antibody directed against the CD20 antigen. Ibritumomab tiuxetan is a clear, colorless, sterile,
pyrogen-free, preservative-free solution that may contain translucent particles. Each single-use vial includes 3.2 mg of ibritumomab
tiuxetan in 2 mL of 0.9% Sodium Chloride. Physical/Radiochemical Characteristics of Y-90 Yttrium-90 decays by emission of β parti-
cles, with a physical half-life of 64.1 hours (2.67 days). The product of radioactive decay is non-radioactive Zirconium-90. The range of
β particles in soft tissue (χ 90 ) is 5 mm.
Indications
Zevalin is a CD20-directed radiotherapeutic antibody administered as part of the Zevalin therapeutic regimen indicated for the treat-
ment of adult patients with:
relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL)
previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy

Key Patent
Number: 5,776,456

10,799,597 expires 9/10/2038 - Subcutaneous administration of antibody-drug conjugates for cancer therapy
10,918,734 expires 25/7/2038 - Treatment of high Trop-2 expressing triple negative breast cancer (TNBC) with sacituzumab govitecan
(IMMU-132) overcomes homologous recombination repair (HRR) rescue mediated by Rad51
10,266,605 expires 5/9/2037 - Efficacy of anti-trop-2-SN-38 antibody drug conjugates for therapy of tumors relapsed/refractory to
checkpoint inhibitors
10,954,305 expires 30/4/2037 - Combination of ABCG2 inhibitors with sacituzumab govitecan (IMMU-132) overcomes resistance to
SN-38 in Trop-2 expressing cancers
10,195,175 expires 23/6/2036 - Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative
breast cancer when used with microtubule inhibitors or PARP inhibitors
10,413,539 expires 13/11/2033 - Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan
(IMMU-132)
10,744,129 expires 2/10/2033 - Therapy of small-cell lung cancer (SCLC) with a topoisomerase-I inhibiting antibody-drug conjugate
(ADC) targeting Trop-2
10,034,950 expires 23/7/2033 - Antibody-SN-38 immunoconjugates with a CL2A linker
10,130,718 expires 23/7/2033 - Antibody-drug conjugates and uses thereof
9,707,302 expires 23/7/2033 - Combining anti-HLA-DR or anti-Trop-2 antibodies with microtubule inhibitors, PARP inhibitors, bru-
ton kinase inhibitors or phosphoinositide 3-kinase inhibitors significantly improves therapeutic outcome in cancer
9,770,517 expires 3/3/2023 - Anti-Trop-2 antibody-drug conjugates and uses thereof
8,021,856 expires 29/11/2020 - Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
6,451,284 expires 26/7/2020 - Clinical parameters for determining hematologic toxicity prior to radioimmunotheraphy
7,195,750 expires 26/7/2020 - Clinical parameters for determining hematologic toxicity prior to radioimmunotherapy
9,139,654 expires 5/1/2020 - Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
7,381,560 expires 22/9/2016 - Expression and use of anti-CD20 antibodies
Sun Pharma
Ilumya
35,000 30
30,000 25
25,000
20
20,000
15
15,000
10
10,000
5,000 5
5 5 5 5
0 0 0 0 0 0
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Ilumya Median
Description
Tildrakizumab-asmn is a humanized IgG1/k antibody that specifically binds to the p19 subunit of interleukin-23 (IL-23). Tildraki-
zumab-asmn is produced in a recombinant Chinese hamster ovary (CHO) cell line and has an approximate molecular mass of 147
kilodaltons. Ilumya (tildrakizumab-asmn) injection, for subcutaneous use, is a sterile, clear to slightly opalescent, colorless to slightly
yellow solution.
Indications
Ilumya is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or
phototherapy.

Key Patent
Number: 8,293,883
Takeda
Elaprase
120,000 30
100,000 25
80,000 20
60,000 15
40,000 10
20,000 7 5
6 6 6 6 6
5 5 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Elaprase Median
Description
Elaprase is a formulation of idursulfase, a purified form of human iduronate-2-sulfatase, a lysosomal enzyme. Idursulfase is pro-
duced by recombinant DNA technology in a human cell line. Idursulfase is an enzyme that hydrolyzes the 2-sulfate esters of terminal
iduronate sulfate residues from the glycosaminoglycans dermatan sulfate and heparan sulfate in the lysosomes of various cell types.
Idursulfase is a 525-amino acid glycoprotein with a molecular weight of approximately 76 kilodaltons. The enzyme contains eight
asparagine-linked glycosylation sites occupied by complex oligosaccharide structures. The enzyme activity of idursulfase is dependent
on the post-translational modification of a specific cysteine to formylglycine.
Indications
Elaprase is indicated for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II).

Key Patent
Number: 5,932,211
Entyvio
900,000 30
800,000
25
700,000
600,000 20
500,000
15
400,000
300,000 10
200,000
7 5
100,000 6 6 6 6 6
5 5 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Entyvio Median
Description
Vedolizumab, an integrin receptor antagonist, is a humanized IgG 1 monoclonal antibody produced in Chinese hamster ovary cells
that binds to the human a4β7 integrin. Entyvio has an approximate molecular weight of 147 kilodaltons.
Indications
Entyvio is indicated in adults for the treatment of:
moderately to severely active ulcerative colitis.
Moderately to severely active Crohn's disease.

Key Patent
Number: 7,147,851

Kalbitor
7,000 30
6,000 25
5,000
20
4,000
15
3,000
10
2,000
1,000 5
6
5 5 5 5 5
4 4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Kalbitor Median
Description
Kalbitor (ecallantide) is a human plasma kallikrein inhibitor for injection for subcutaneous use. Ecallantide is a 60-amino-acid protein
produced in Pichia pastoris yeast cells by recombinant DNA technology.
Indications
Kalbitor (ecallantide) is indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older.

Key Patent
Number: 7,276,480
Natpara
50,000 30
45,000
25
40,000
35,000
20
30,000
25,000 15
20,000
10
15,000
10,000
7 5
6 6 6 6
5,000 5 5 5 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Natpara Median
Description
The active ingredient in Natpara, parathyroid hormone, is produced by recombinant DNA technology using a modified strain of
Escherichia coli . Parathyroid hormone has 84 amino acids and a molecular weight of 9425 daltons.
Indications
Natpara is a parathyroid hormone indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hy-
poparathyroidism.

Key Patent
Number: 5,496,801
Takhzyro
300,000 30
250,000 25
200,000 20
150,000 15
100,000 10
50,000 7 5
6 6 6 6 6
5 5 5 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Takhzyro Median
Description
Lanadelumab-flyo is non-plasma derived, recombinant, fully human, monoclonal antibody (IgG1/κ-light chain) produced in Chinese
Hamster Ovary (CHO) cells. Based on the amino acid sequence, the molecular weight of the non-glycosylated lanadelumab-flyo is 146
kDa. The calculated molecular mass of the fully reduced light chain is 23 kDa. The calculated molecular mass of the fully reduced and
non-glycosylated heavy chain is 49 kDa.
Indications
Takhzyro is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years and older. T

Key Patent
Number: 8,816,055

Vpriv
Description
Velaglucerase alfa is a hydrolytic lysosomal glucocerebroside-specific enzyme produced by gene activation technology in a human
fibroblast cell line. Velaglucerase alfa is a glycoprotein of 497 amino acids and a molecular weight of approximately 63 kDa. Velaglu-
cerase alfa has the same amino acid sequence as the naturally occurring human enzyme, glucocerebrosidase. Velaglucerase alfa con-
tains five potential N-linked glycosylation sites; four of these sites are occupied by glycan chains. Velaglucerase alfa contains predom-
inantly high mannose-type N-linked glycan chains. The high mannose type N-linked glycan chains are specifically recognized and
internalized via the mannose receptor present on the surface on macrophages, the cells that accumulate glucocerebroside in Gaucher
disease.
Indications
VPRIV is indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease.

Key Patent
Number: 7,138,262

9,623,090 expires 1/3/2033 - Compositions and methods for treating type III gaucher disease
9,453,847 expires 19/7/2031 - Mannose receptor C type 1 (MRC1) codon optimized cell line and uses thereof
9,694,057 expires 6/2/2027 - Stabilized compositions of proteins having a free thiol moiety
Teva
Ajovy
1,200 30
1,000 25
800 20
600 15
400 10
10 10 10
200 5
6 6
2 2 1 1 1
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Ajovy Median
Description
Fremanezumab-vfrm is a fully humanized IgG2δa/κ monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand.
Fremanezumab-vfrm is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. The antibody consists of
1324 amino acids and has a molecular weight of approximately 148 kDa.
Indications
Ajovy is indicated for the preventive treatment of migraine in adults.

Key Patent
Number: 8,007,794

10,899,826 expires 12/9/2039 - Pharmaceutical compositions for an anti-CGRP antagonist antibody
10,392,434 expires 22/9/2037 - Treating refractory migraine
10,519,224 expires 20/3/2035 - Treating headache comprising administering an antibody to calcitonin gene-related peptide
10,066,009 expires 21/5/2032 - Anti-CGRP compositions and use thereof
Cinqair
Description
Cinqair (reslizumab) is a humanized interleukin-5 antagonist monoclonal antibody (IgG4κ). Reslizumab is produced by recombinant
DNA technology in murine myeloma non-secreting 0 (NS0) cells. Reslizumab has a molecular weight of approximately 147 kDa.
Indications
Cinqair is indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophil-
ic phenotype

Key Patent
Number:

Theratechnologies
Egrifta
Description
Egrifta SV contains tesamorelin (as the acetate salt), a human growth hormone-releasing factor (GRF) analog. The peptide precursor
of tesamorelin acetate is produced synthetically and is comprised of the 44 amino acid sequence of human GRF. Tesamorelin acetate is
made by attaching a hexenoyl moiety, a C6 chain with a double bond at position 3, to the tyrosine residue at the N-terminal part of the
molecule.
Indications
Egrifta SV is indicated for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy.

Key Patent
Number: 5,861,379
Trogarzo
Description
Trogarzo is a CD4-directed post-attachment HIV-1 inhibitor. Ibalizumab-uiyk is a CD4 domain 2-directed humanized monoclonal
antibody of immunoglobulin G (IgG) isotype 4 with a molecular weight of approximately 150 kDa. Ibalizumab-uiyk is produced by
recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells.
Indications
Trogarzo, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1)
infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.

Key Patent
Number: 5,871,732
UCB
Cimzia
2,500 30
25
2,000
20
1,500
15
1,000
10
10
500 8 8 8 8 8
5
6
5 5
4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Cimzia Median
Description
Certolizumab pegol is a TNF blocker. Cimzia is a recombinant, humanized antibody Fab' fragment, with specificity for human tumor
necrosis factor α (TNFa), conjugated to an approximately 40kDa polyethylene glycol (PEG2MAL40K). The Fab' fragment is manufac-
tured in E. coli and is subsequently subjected to purification and conjugation to PEG2MAL40K, to generate certolizumab pegol. The
Fab' fragment is composed of a light chain with 214 amino acids and a heavy chain with 229 amino acids. The molecular weight of
certolizumab pegol is approximately 91 kiloDaltons.
Indications
Cimzia is indicated for:
Reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely
active disease who have had an inadequate response to conventional therapy
Treatment of adults with moderately to severely active rheumatoid arthritis
Treatment of adult patients with active psoriatic arthritis.
Treatment of adults with active ankylosing spondylitis
Treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation
Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy

Key Patent
Number: 7,012,135
Ultragenyx
Crysvita
1,200 30
1,000 25
800 20
600 15
400 10
11
10 10 10 10 10 10 10
8
200 7 5
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Crysvita Median
Description
Burosumab-twza is a human immunoglobulin G subclass 1 (IgG1), anti-human fibroblast growth factor 23 (FGF23) antibody
produced by recombinant DNA technology using Chinese hamster ovary cells. Burosumab-twza is composed of two heavy chain (γ1-
chain) molecules and two light chain (κ-chain) molecules. Each heavy chain has an N-linked carbohydrate moiety at asparagine 297
(Asn297). The molecular weight of burosumab-twza determined by mass spectrometry is approximately 147,000.
Indications
Crysvita is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for:
The treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.
The treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal
tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

Key Patent
Number: 7,883,705

10,639,360 expires 29/5/2035 - Methods for treating hypophosphatemic disorders
Mepsevii
90 30
80
25
70
60 20
50
15
40
30 10
11 11 11 11 11 11 11 11
10
20
7 5
10
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Mepsevii Median
Description
Vestronidase alfa-vjbk is a recombinant human lysosomal β glucuronidase which is a purified human enzyme produced by recombi-
nant DNA technology in a Chinese hamster ovary cell line. Purified vestronidase alfa-vjbk exists as a homotetramer, with each mon-
omer consisting of 629 amino acids. The calculated isotope average molecular mass of each non-glycosylated peptide chain is 72,562
Da. The amino acid sequence for vestronidase alfa-vjbk is the same as the amino acid sequence for human β-glucuronidase (GUS).
Indications
Mepsevii is indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).

Key Patent
Number: 9,457,067

9,937,243 expires 5/3/2035 - Sialylated glycoprotein compositions and uses thereof
Y-Mabs
Danyelza
600 30
500 25
400 20
300 15
200 10
100 5
5 5 5 5 5
4 4 4 4 4
0 0
2021 2022 2023 2024 2025 2026 2027 2028 2029 2030
Forecasts Naxitamab Median
Description
Naxitamab-gqgk is a glycolipid disialoganglioside (GD2)-binding recombinant humanized monoclonal IgG1 antibody, that contains
human framework regions and murine complementarity-determining regions. Naxitamab-gqgk is produced in a Chinese hamster
ovary cell line and has an approximate molecular weight of 144 kDa without glycosylation.
Indications
Danyelza is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediat-
ric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow
who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accel-
erated approval based on overall response rate and duration of response

Key Patent
Number: 9,315,585

10,167,341 expires 12/8/2034 - High affinity anti-GD2 antibodies
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Biologic Drugs: Black Is The New Orange

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Biologic Drugs

Black is the New Orange

SIMON BAKER BIOPHARMACEUTICALS 15 OCTOBER 2021

T +44 20 7000 2072

T +44 20 7000 2089

One cannot value a pharma company without knowing when generic or

Important note: see regulatory disclosures on page 192 of this report. 3

The idea .......................................................................................................................... 5

4 Important note: see regulatory disclosures on page 192 of this report.

Fig 1: Biologics as a proportion of global pharma sales, 2010-26E

New modalities Vaccines Monoclonal antibodies Recombinant proteins Other

Source: Redburn, Evaluate Pharma

Important note: see regulatory disclosures on page 192 of this report. 5

Fig 2: US sales of biologic drugs in the year of lost exclusivity

Also, as a general principle, we have based expected biosimilar competition on patent

6 Important note: see regulatory disclosures on page 192 of this report.

Fig 4: Proportion of sales exposed to generics or biologics in the year of impact

Biologic Small molecule Vaccine

Important note: see regulatory disclosures on page 192 of this report. 7

AstraZeneca (Buy, fair value 12,700p)

A good example of this is Lynparza, Astra’s class-leading DNA damage repair

8 Important note: see regulatory disclosures on page 192 of this report.

Fig 5: AstraZeneca marketed portfolio expiry profile

GlaxoSmithKline (Buy, fair value 2,140p)

Fig 6: GSK marketed portfolio expiry profile

Important note: see regulatory disclosures on page 192 of this report. 9

Fig 7: Glaxo’s long-term revenue aspirations

Novartis (Buy, fair value CHF126)

10 Important note: see regulatory disclosures on page 192 of this report.

Fig 8: Novartis marketed portfolio expiry profile

Roche (Buy, fair value CHF 430)

Important note: see regulatory disclosures on page 192 of this report. 11

Fig 9: Roche marketed portfolio expiry profile

UCB (Buy, fair value €136)

12 Important note: see regulatory disclosures on page 192 of this report.

Fig 10: UCB marketed portfolio expiry profile

Merck KGaA (Buy, fair value €184)

Fig 11: Merck KGaA marketed portfolio expiry profile

Novo Nordisk (Neutral, fair value DKK510)

Important note: see regulatory disclosures on page 192 of this report. 13

Fig 12: Novo Nordisk marketed portfolio expiry profile

Ipsen (Neutral, fair value €99)

Fig 13: Ipsen marketed portfolio expiry profile

14 Important note: see regulatory disclosures on page 192 of this report.

Sanofi (Neutral, fair value €93)

Fig 14: Sanofi marketed portfolio expiry profile

Important note: see regulatory disclosures on page 192 of this report. 15

Fig 15: European pharma summary multiples and valuations

16 Important note: see regulatory disclosures on page 192 of this report.

Patent and exclusivity data

Important note: see regulatory disclosures on page 193 of this report. 17

01/ Patent and exclusivity data

How we assembled the data

18 Important note: see regulatory disclosures on page 192 of this report.

01/ Patent and exclusivity data

Important note: see regulatory disclosures on page 192 of this report. 19

Approval and Data Exclusivity

Patents citing, and expiring after, the key patent

There are no patents citing the key patent.

Important note: see regulatory disclosures on page 192 of this report. 3