AR102417A1 - Anticuerpos biespecíficos anti-tnf- / anti-il-23 - Google Patents
Anticuerpos biespecíficos anti-tnf- / anti-il-23Info
- Publication number
- AR102417A1 AR102417A1 ARP150103442A ARP150103442A AR102417A1 AR 102417 A1 AR102417 A1 AR 102417A1 AR P150103442 A ARP150103442 A AR P150103442A AR P150103442 A ARP150103442 A AR P150103442A AR 102417 A1 AR102417 A1 AR 102417A1
- Authority
- AR
- Argentina
- Prior art keywords
- seq
- amino acid
- acid sequence
- scfv
- hcvr2
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Los anticuerpos biespecíficos son útiles para el tratamiento de varias enfermedades autoinmunitarias que incluyen la enfermedad inflamatoria intestinal, tal como la enfermedad de Crohn y la colitis ulcerosa, espondiloartritis axial, artritis reumatoide y artritis psoriásica. Reivindicación 1: Un anticuerpo biespecífico que comprende un anticuerpo de inmunoglobulina (IgG) que se une al factor de necrosis tumoral a (TNFa) conjugado con dos fragmentos variables de cadena simple (scFv) que se unen a la subunidad p19 de IL-23 (IL23p19) donde, a) dicha IgG comprende dos cadenas pesadas (HC) y dos cadenas ligeras (LC), cada HC comprende una región variable de cadena pesada (HCVR1) que comprende CDR de cadena pesada (HCDR) 1 - 3 y cada LC comprende una región variable de cadena ligera (LCVR1) que comprende CDR de cadena ligera (LCDR) 1 - 3, donde la secuencia de aminoácidos de HCDR1 es la SEQ ID Nº 9, la secuencia de aminoácidos de HCDR2 es la SEQ ID Nº 10, la secuencia de aminoácidos de HCDR3 es la SEQ ID Nº 11, la secuencia de aminoácidos de LCDR1 es la SEQ ID Nº 15, la secuencia de aminoácidos de LCDR2 es la SEQ ID Nº 16, y la secuencia de aminoácidos de LCDR3 es la SEQ ID Nº 17; y b) cada scFv comprende una región variable de cadena pesada (HCVR2) y una región variable de cadena ligera (LCVR2), la HCVR2 comprende las HCDR 4 - 6 y la LCVR2 comprende las LCDR 4 - 6, donde la secuencia de aminoácidos de HCDR4 es la SEQ ID Nº 12, la secuencia de aminoácidos de HCDR5 es la SEQ ID Nº 13, la secuencia de aminoácidos de HCDR6 es la SEQ ID Nº 14, la secuencia de aminoácidos de LCDR4 es la SEQ ID Nº 18, la secuencia de aminoácidos de LCDR5 es la SEQ ID Nº 19, y la secuencia de aminoácidos de LCDR6 es la SEQ ID Nº 20, donde cada scFv está independientemente conjugado con dicho anticuerpo de IgG a través de un enlazador polipeptídico (L1) unido de forma covalente al extremo C de cada HC de IgG y el extremo N de la HCVR2 de cada scFv, y la HCVR2 de cada scFv está unida de forma covalente a la LCVR2 del mismo scFv a través de un segundo enlazador polipeptídico (L2) unido de forma covalente al extremo C de la HCVR2 y el extremo N de la LCVR2 del mismo scFv. Reivindicación 4: Una molécula de ADN que comprende una secuencia de polinucleótidos que codifica una cadena de polipéptidos que comprende una HC, un scFv, un enlazador polipeptídico y un segundo enlazador polipeptídico del anticuerpo biespecífico de cualquiera de las reivindicaciones 1 - 3. Reivindicación 10: Una célula de mamífero que comprende la molécula de ADN de cualquiera de las reivindicaciones 4 - 9.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462075571P | 2014-11-05 | 2014-11-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR102417A1 true AR102417A1 (es) | 2017-03-01 |
Family
ID=54477413
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP150103442A AR102417A1 (es) | 2014-11-05 | 2015-10-23 | Anticuerpos biespecíficos anti-tnf- / anti-il-23 |
Country Status (9)
Country | Link |
---|---|
US (1) | US9718884B2 (es) |
EP (1) | EP3215529A1 (es) |
JP (1) | JP2017533705A (es) |
CN (1) | CN108064249A (es) |
AR (1) | AR102417A1 (es) |
CA (1) | CA2959551C (es) |
MA (1) | MA40901A (es) |
TW (1) | TWI585105B (es) |
WO (1) | WO2016073406A1 (es) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR112018007214A2 (pt) * | 2015-10-30 | 2018-10-16 | Lilly Co Eli | anticorpos biespecíficos anti-cgrp/anti-il-23 e usos destes |
TW201902926A (zh) * | 2017-05-03 | 2019-01-16 | 美商美國禮來大藥廠 | 抗cgrp/抗il-23雙特異性抗體及其用途 |
AR112341A1 (es) * | 2017-08-02 | 2019-10-16 | Lilly Co Eli | ANTICUERPOS BIESPECÍFICOS ANTI-TNF- / ANTI-IL-23 DE IgG |
CN108640997A (zh) * | 2018-05-22 | 2018-10-12 | 蔡毓旻 | 一种双特异性抗体 |
KR102088789B1 (ko) * | 2018-06-20 | 2020-03-13 | 인하대학교 산학협력단 | 항 TNF/IFN scFv-Fc 이중 표적 항체 및 이의 이용 |
TWI722535B (zh) | 2018-08-21 | 2021-03-21 | 美商美國禮來大藥廠 | 測定蛋白質或肽濃度的方法及其用途 |
AU2019386021B2 (en) | 2018-11-27 | 2024-02-15 | Innovent Biologics (Suzhou) Co., Ltd. | Anti-il-23p19 antibody and uses thereof |
CA3138241A1 (en) * | 2019-05-23 | 2020-11-26 | Janssen Biotech, Inc. | Method of treating inflammatory bowel disease with a combination therapy of antibodies to il-23 and tnf alpha |
CA3163877A1 (en) | 2019-12-06 | 2021-06-10 | Ablynx Nv | Polypeptides comprising immunoglobulin single variable domains targeting tnf.alpha. and il-23 |
CN115605231A (zh) * | 2020-05-13 | 2023-01-13 | 信达生物制药(苏州)有限公司(Cn) | 包含抗IL-23p19抗体的制剂、其制备方法和用途 |
US20210363234A1 (en) * | 2020-05-21 | 2021-11-25 | Janssen Biotech, Inc. | Method of Treating Inflammatory Bowel Disease with a Combination Therapy of Antibodies to IL-23 and TNF Alpha |
CN111718414B (zh) * | 2020-06-12 | 2021-03-02 | 江苏荃信生物医药有限公司 | 抗人白介素23单克隆抗体及其应用 |
AR123477A1 (es) * | 2020-09-10 | 2022-12-07 | Lilly Co Eli | Formulaciones de anticuerpos terapéuticos |
WO2022123293A1 (ko) * | 2020-12-09 | 2022-06-16 | 에이치케이이노엔 주식회사 | 항 OX40L 항체, 항 OX40L 및 항 TNFα 이중 특이성 항체 및 이들의 용도 |
WO2024061288A1 (en) * | 2022-09-21 | 2024-03-28 | Inmagene Biopharmaceuticals (Hangzhou) Co., Ltd. | Antibodies targeting tnf alpha and il-23 and uses thereof |
CN117534732B (zh) * | 2023-11-03 | 2024-10-22 | 湖南中晟全肽生物科技股份有限公司 | 一种抑制il-12与其受体结合的多肽及其应用 |
Family Cites Families (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
KR20140094647A (ko) | 1999-03-25 | 2014-07-30 | 아비에 도이치란트 게엠베하 운트 콤파니 카게 | 사람 il-12에 결합하는 사람 항체 및 이의 제조방법 |
WO2001077342A1 (en) | 2000-04-11 | 2001-10-18 | Genentech, Inc. | Multivalent antibodies and uses therefor |
US7422743B2 (en) | 2000-05-10 | 2008-09-09 | Schering Corporation | Mammalian receptor protein DCRS5;methods of treatment |
DK1576011T3 (da) | 2002-10-30 | 2009-11-30 | Genentech Inc | Inhibering af IL-17 produktion |
ATE515514T1 (de) | 2002-12-23 | 2011-07-15 | Schering Corp | Verwendungen von säuger-cytokin il-23 ; verwandte reagenzien |
JP4605798B2 (ja) | 2003-03-10 | 2011-01-05 | シェーリング コーポレイション | Il−23アゴニストおよびil−23アンタゴニスト;関連試薬の使用 |
TWI363091B (en) | 2004-12-20 | 2012-05-01 | Schering Corp | Uses of mammalian cytokine; related reagents |
SI1896073T1 (sl) | 2005-06-30 | 2013-06-28 | Janssen Biotech, Inc. | Protitelesa proti il-23, sestavki, prostopki in uporabe |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
WO2007024846A2 (en) | 2005-08-25 | 2007-03-01 | Eli Lilly And Company | Anit-il-23 antibiodies |
US7807160B2 (en) | 2005-08-31 | 2010-10-05 | Schering Corporation | Engineered anti-IL-23 antibodies |
DK1933869T3 (da) * | 2005-09-01 | 2010-03-01 | Schering Corp | Anvendelse af IL-23- og IL-17-antagonister til behandling af autoimmun øjenbetændelsessygdom |
US7935344B2 (en) | 2005-12-29 | 2011-05-03 | Centocor Ortho Biotech Inc. | Human anti-IL-23 antibodies, compositions, methods and uses |
CA2655372A1 (en) | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
US20100303777A1 (en) * | 2006-12-14 | 2010-12-02 | Actogenix N.V. | Delivery of binding molecules to induce immunomodulation |
JP2010518858A (ja) * | 2007-02-23 | 2010-06-03 | シェーリング コーポレイション | 操作された抗−il−23p19抗体 |
SI2059534T1 (sl) | 2007-02-23 | 2012-08-31 | Schering Corp | Umetno proizvedena anti-il-23p19 antitelesa |
WO2008106131A2 (en) | 2007-02-28 | 2008-09-04 | Schering Corporation | Combination therapy for treatment of immune disorders |
SI2274008T1 (sl) * | 2008-03-27 | 2014-08-29 | Zymogenetics, Inc. | Sestavki in metode za zaviranje PDGFRBETA in VEGF-A |
RU2010153580A (ru) | 2008-06-03 | 2012-07-20 | Эбботт Лэборетриз (Us) | Иммуноглобулины с двумя вариабельными доменами и их применение |
AU2009288419B2 (en) | 2008-08-27 | 2015-08-06 | Merck Sharp & Dohme Llc | Lyophilized formulatons of engineered anti-IL-23p19 antibodies |
EP2352762A1 (en) | 2008-11-03 | 2011-08-10 | Schering Corporation | Inflammatory bowel disease biomarkers and related methods of treatment |
JP5795759B2 (ja) * | 2009-04-16 | 2015-10-14 | アッヴィ・バイオセラピューティクス・インコーポレイテッド | 抗TNF−α抗体およびその用途 |
WO2011017294A1 (en) * | 2009-08-07 | 2011-02-10 | Schering Corporation | Human anti-rankl antibodies |
GB201013975D0 (en) * | 2010-08-20 | 2010-10-06 | Imp Innovations Ltd | Method of treating desease |
RU2012147249A (ru) * | 2010-04-07 | 2014-05-20 | Эббви Инк. | TNF-α- СВЯЗЫВАЮЩИЕ БЕЛКИ |
WO2012009760A1 (en) | 2010-07-20 | 2012-01-26 | Cephalon Australia Pty Ltd | Anti-il-23 heterodimer specific antibodies |
AR084210A1 (es) * | 2010-12-08 | 2013-05-02 | Abbott Lab | PROTEINAS DE UNION AL TNF-a |
TWI838039B (zh) | 2011-03-28 | 2024-04-01 | 法商賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
RU2014121043A (ru) | 2011-10-24 | 2015-12-10 | Эббви Инк. | Биспецифические иммуносвязывающие средства, направленные против tnf и il-17 |
US20140212425A1 (en) * | 2011-12-05 | 2014-07-31 | Immunomedics, Inc. | Therapeutic use of anti-cd22 antibodies for inducing trogocytosis |
WO2013123061A1 (en) * | 2012-02-13 | 2013-08-22 | Seattle Children's Hospital D/B/A Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
AR090626A1 (es) | 2012-04-20 | 2014-11-26 | Lilly Co Eli | Anticuerpos anti-baff-anti-il-17 biespecificos |
US20150158943A1 (en) * | 2012-06-01 | 2015-06-11 | Momenta Pharmaceuticals, Inc. | Methods related to adalimumab |
US20150322519A1 (en) | 2012-12-21 | 2015-11-12 | Joshua MICELWEE | Biomarkers for psoriasis treatment response |
TW201444867A (zh) | 2013-03-08 | 2014-12-01 | Lilly Co Eli | 抗tnf-抗il-17雙特異性抗體 |
JOP20140049B1 (ar) * | 2013-03-08 | 2021-08-17 | Lilly Co Eli | أجسام مضادة ترتبط بـ il-23 |
CN105307675A (zh) | 2013-03-15 | 2016-02-03 | 美国安进公司 | 使用抗il23抗体治疗克罗恩氏病的方法 |
CA2959629C (en) * | 2014-09-03 | 2023-10-31 | Boehringer Ingelheim International Gmbh | Compound targeting il-23a and tnf-alpha and uses thereof |
-
2015
- 2015-10-23 AR ARP150103442A patent/AR102417A1/es unknown
- 2015-10-26 TW TW104135138A patent/TWI585105B/zh not_active IP Right Cessation
- 2015-11-02 MA MA040901A patent/MA40901A/fr unknown
- 2015-11-03 WO PCT/US2015/058719 patent/WO2016073406A1/en active Application Filing
- 2015-11-03 US US14/930,678 patent/US9718884B2/en not_active Expired - Fee Related
- 2015-11-03 CN CN201580059953.8A patent/CN108064249A/zh active Pending
- 2015-11-03 CA CA2959551A patent/CA2959551C/en not_active Expired - Fee Related
- 2015-11-03 EP EP15791228.8A patent/EP3215529A1/en not_active Withdrawn
- 2015-11-03 JP JP2017523213A patent/JP2017533705A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
MA40901A (fr) | 2017-09-12 |
TW201627321A (zh) | 2016-08-01 |
EP3215529A1 (en) | 2017-09-13 |
CA2959551A1 (en) | 2016-05-12 |
CN108064249A (zh) | 2018-05-22 |
US20160122429A1 (en) | 2016-05-05 |
US9718884B2 (en) | 2017-08-01 |
JP2017533705A (ja) | 2017-11-16 |
CA2959551C (en) | 2018-09-11 |
TWI585105B (zh) | 2017-06-01 |
WO2016073406A1 (en) | 2016-05-12 |
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