SG11201900885VA - Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule - Google Patents
Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage moleculeInfo
- Publication number
- SG11201900885VA SG11201900885VA SG11201900885VA SG11201900885VA SG11201900885VA SG 11201900885V A SG11201900885V A SG 11201900885VA SG 11201900885V A SG11201900885V A SG 11201900885VA SG 11201900885V A SG11201900885V A SG 11201900885VA SG 11201900885V A SG11201900885V A SG 11201900885VA
- Authority
- SG
- Singapore
- Prior art keywords
- international
- antigen
- street
- pro
- inhibitor
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title abstract 4
- 239000003112 inhibitor Substances 0.000 title abstract 3
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 title abstract 2
- 210000004322 M2 macrophage Anatomy 0.000 title abstract 2
- 201000011510 cancer Diseases 0.000 title abstract 2
- 239000000427 antigen Substances 0.000 abstract 4
- 108091007433 antigens Proteins 0.000 abstract 4
- 102000036639 antigens Human genes 0.000 abstract 4
- 239000003795 chemical substances by application Substances 0.000 abstract 3
- 239000000203 mixture Substances 0.000 abstract 2
- 241000218657 Picea Species 0.000 abstract 1
- 210000001744 T-lymphocyte Anatomy 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 210000002540 macrophage Anatomy 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 238000001565 modulated differential scanning calorimetry Methods 0.000 abstract 1
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 abstract 1
- 230000008520 organization Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/11—Antigen recognition domain
- A61K2239/13—Antibody-based
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/48—Blood cells, e.g. leukemia or lymphoma
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001104—Epidermal growth factor receptors [EGFR]
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001111—Immunoglobulin superfamily
- A61K39/001112—CD19 or B4
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001129—Molecules with a "CD" designation not provided for elsewhere
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001166—Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
- A61K39/001168—Mesothelin [MSLN]
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464403—Receptors for growth factors
- A61K39/464404—Epidermal growth factor receptors [EGFR]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464411—Immunoglobulin superfamily
- A61K39/464412—CD19 or B4
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464416—Receptors for cytokines
- A61K39/464419—Receptors for interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
- C07K16/2803—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 immunoglobulin superfamily
-
- 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
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
-
- 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
-
- 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
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Genetics & Genomics (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Developmental Biology & Embryology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 08 February 2018 (08.02.2018) WIP0 I PCT ~~ll~~~~~~~~ 011101010VIIIOH olo oliolomu om (10) International Publication Number WO 2018/026819 A3 W O 20 18/0268 19 A3 (51) International Patent Classification: A61K 39/00 (2006.01) C07K 16/28 (2006.01) CO7K 16/24 (2006.01) (21) International Application Number: PCT/US2017/044909 (22) International Filing Date: 01 August 2017 (01.08.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/369,589 01 August 2016 (01.08.2016) US (71) Applicants: NOVARTIS AG [CH/CH]; Lichtstrasse 35, 4056 Basel (CH). THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA [US/US]; 3160 Chesnut Street, Suite 200, Philadelphia, PA 19104 (US). (72) Inventors: GILL, Saar; 30 North 6rd Street, Apt. 4A, Philadelphia, PA 19106 (US). RUELLA, Marco; 730 Cricket Ave, Ardmore, PA 19003 (US). KLICHINSKY, Michael; 1810 Spruce Street, Philadelphia, PA 19103 (US). (74) Agent: COLLAZO, Diana, M. et al.; Lando & Anastasi, LLP, Riverfront Office Park, One Main Street, Suite 1100, Cambridge, MA 02142 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: with international search report (Art. 21(3)) before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) with sequence listing part of description (Rule 5.2(a)) (88) Date of publication of the international search report: 08 March 2018 (08.03.2018) (54) Title: TREATMENT OF CANCER USING A CHIMERIC ANTIGEN RECEPTOR IN COMBINATION WITH AN INHIBITOR OF A PRO-M2 MACROPHAGE MOLECULE (57) : The invention provides compositions and methods for treating diseases associated with expression of an antigen, e.g., a solid tumor antigen or antigen expressed on a tumor associated with TAMs and/or MDSCs, by administering a recombinant T cell comprising a CAR binding to said antigen, as described herein, in combination with an inhibitor of a pro-M2 macrophage molecule, e.g., described herein. The invention also provides kits and compositions described herein.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662369589P | 2016-08-01 | 2016-08-01 | |
PCT/US2017/044909 WO2018026819A2 (en) | 2016-08-01 | 2017-08-01 | Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule |
Publications (1)
Publication Number | Publication Date |
---|---|
SG11201900885VA true SG11201900885VA (en) | 2019-02-27 |
Family
ID=59684040
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG11201900885VA SG11201900885VA (en) | 2016-08-01 | 2017-08-01 | Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule |
Country Status (13)
Country | Link |
---|---|
US (1) | US20190161542A1 (en) |
EP (1) | EP3490590A2 (en) |
JP (2) | JP2019527696A (en) |
KR (1) | KR20190036551A (en) |
CN (1) | CN110267677A (en) |
AU (1) | AU2017306267A1 (en) |
BR (1) | BR112019002035A2 (en) |
CA (1) | CA3032581A1 (en) |
IL (1) | IL264588A (en) |
MX (1) | MX2019001469A (en) |
RU (1) | RU2019105693A (en) |
SG (1) | SG11201900885VA (en) |
WO (1) | WO2018026819A2 (en) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2013222284A1 (en) * | 2012-02-22 | 2014-08-07 | The Trustees Of The University Of Pennsylvania | Use of the CD2 signaling domain in second-generation chimeric antigen receptors |
EP3626741A1 (en) | 2013-02-20 | 2020-03-25 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
WO2014130635A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
EP3623380A1 (en) | 2013-03-15 | 2020-03-18 | Michael C. Milone | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
UY35468A (en) | 2013-03-16 | 2014-10-31 | Novartis Ag | CANCER TREATMENT USING AN ANTI-CD19 CHEMERIC ANTIGEN RECEIVER |
US10287354B2 (en) | 2013-12-20 | 2019-05-14 | Novartis Ag | Regulatable chimeric antigen receptor |
US11028143B2 (en) | 2014-01-21 | 2021-06-08 | Novartis Ag | Enhanced antigen presenting ability of RNA CAR T cells by co-introduction of costimulatory molecules |
EP3172234B1 (en) | 2014-07-21 | 2020-04-08 | Novartis AG | Treatment of cancer using a cd33 chimeric antigen receptor |
MX2017001011A (en) | 2014-07-21 | 2018-05-28 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor. |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
SG11201700418VA (en) | 2014-07-21 | 2017-02-27 | Novartis Ag | Treatment of cancer using a cll-1 chimeric antigen receptor |
TW202140557A (en) | 2014-08-19 | 2021-11-01 | 瑞士商諾華公司 | Treatment of cancer using a cd123 chimeric antigen receptor |
KR20210149228A (en) | 2014-09-17 | 2021-12-08 | 노파르티스 아게 | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
AU2015330898B2 (en) | 2014-10-08 | 2022-03-10 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
WO2016115482A1 (en) | 2015-01-16 | 2016-07-21 | Novartis Pharma Ag | Phosphoglycerate kinase 1 (pgk) promoters and methods of use for expressing chimeric antigen receptor |
US11161907B2 (en) | 2015-02-02 | 2021-11-02 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
TWI746437B (en) | 2015-04-08 | 2021-11-21 | 瑞士商諾華公司 | Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car)- expressing cell |
CN108473957B (en) | 2015-04-17 | 2024-07-16 | 诺华股份有限公司 | Methods for improving the efficacy and expansion of chimeric antigen receptor expressing cells |
US12128069B2 (en) | 2015-04-23 | 2024-10-29 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
AU2016297014B2 (en) | 2015-07-21 | 2021-06-17 | Novartis Ag | Methods for improving the efficacy and expansion of immune cells |
US11667691B2 (en) | 2015-08-07 | 2023-06-06 | Novartis Ag | Treatment of cancer using chimeric CD3 receptor proteins |
WO2017040930A2 (en) | 2015-09-03 | 2017-03-09 | The Trustees Of The University Of Pennsylvania | Biomarkers predictive of cytokine release syndrome |
EA201891338A1 (en) | 2015-12-04 | 2018-12-28 | Новартис Аг | COMPOSITIONS AND METHODS FOR IMMUNICOLOGY |
JP7011600B2 (en) | 2016-01-12 | 2022-01-26 | ジェイムズ リチャード ベレンソン, | Improved method for monitoring the immune status of a subject |
US11325948B2 (en) | 2016-03-19 | 2022-05-10 | Exuma Biotech Corp. | Methods and compositions for genetically modifying lymphocytes to express polypeptides comprising the intracellular domain of MPL |
WO2021042072A1 (en) * | 2019-09-01 | 2021-03-04 | Exuma Biotech Corp. | Methods and compositions for the modification and delivery of lymphocytes |
EP3432924A1 (en) | 2016-03-23 | 2019-01-30 | Novartis AG | Cell secreted minibodies and uses thereof |
TW202340473A (en) | 2016-10-07 | 2023-10-16 | 瑞士商諾華公司 | Treatment of cancer using chimeric antigen receptors |
US11535662B2 (en) | 2017-01-26 | 2022-12-27 | Novartis Ag | CD28 compositions and methods for chimeric antigen receptor therapy |
MX2019011272A (en) | 2017-03-22 | 2019-10-24 | Novartis Ag | Compositions and methods for immunooncology. |
WO2018231944A1 (en) | 2017-06-13 | 2018-12-20 | Berenson James R | Diagnostic, prognostic, and monitoring methods for solid tumor cancers |
MX2020004013A (en) | 2017-10-18 | 2021-01-08 | Novartis Ag | Compositions and methods for selective protein degradation. |
US11608382B2 (en) | 2018-06-13 | 2023-03-21 | Novartis Ag | BCMA chimeric antigen receptors and uses thereof |
JP2021532125A (en) * | 2018-07-23 | 2021-11-25 | オスペダーレ・サン・ラッファエーレ・エッセエッレエッレ | A combination of glycosylation inhibitors to treat cancer and one CAR cell therapy |
WO2020092792A2 (en) * | 2018-10-31 | 2020-05-07 | Oncotracker, Inc. | Method of enhancing immune-based therapy |
CN118546959A (en) | 2019-03-05 | 2024-08-27 | 恩卡尔塔公司 | CD 19-directed chimeric antigen receptor and use thereof in immunotherapy |
BR112021026181A2 (en) * | 2019-06-27 | 2022-02-15 | Verseau Therapeutics Inc | Anti-cd53 compositions and methods to modulate inflammatory myeloid cell phenotypes and uses thereof |
IL292924A (en) | 2019-11-26 | 2022-07-01 | Novartis Ag | Cd19 and cd22 chimeric antigen receptors and uses thereof |
EP4087618A4 (en) * | 2020-01-08 | 2024-07-31 | Univ Texas | A method of engineering natural killer cells to target cd70-positive tumors |
WO2022046730A2 (en) * | 2020-08-25 | 2022-03-03 | Bluebird Bio, Inc. | Bcma chimeric antigen receptors |
IL303567A (en) * | 2020-12-08 | 2023-08-01 | Univ Cornell | Methods of inducing an immunomodulatory tumor response |
KR102631623B1 (en) * | 2021-04-16 | 2024-02-02 | 경북대학교 산학협력단 | Use of olfactory receptor for the inhibition of lactate-induced M2 plarization of tumor-associated macrophages and tumor growth |
WO2023122727A2 (en) * | 2021-12-23 | 2023-06-29 | The Trustees Of The University Of Pennsylvania | Delivery of multi-cytokine signals by overexpression of wild-type or mutant signal transduction molecules |
Family Cites Families (216)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR901228A (en) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Ring gap magnet system |
US4433059A (en) | 1981-09-08 | 1984-02-21 | Ortho Diagnostic Systems Inc. | Double antibody conjugate |
US4444878A (en) | 1981-12-21 | 1984-04-24 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4851332A (en) | 1985-04-01 | 1989-07-25 | Sloan-Kettering Institute For Cancer Research | Choriocarcinoma monoclonal antibodies and antibody panels |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US5869620A (en) | 1986-09-02 | 1999-02-09 | Enzon, Inc. | Multivalent antigen-binding proteins |
JPH021556A (en) | 1988-06-09 | 1990-01-05 | Snow Brand Milk Prod Co Ltd | Hybrid antibody and production thereof |
US5858358A (en) | 1992-04-07 | 1999-01-12 | The United States Of America As Represented By The Secretary Of The Navy | Methods for selectively stimulating proliferation of T cells |
US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
DE3920358A1 (en) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | BISPECIFIC AND OLIGO-SPECIFIC, MONO- AND OLIGOVALENT ANTI-BODY CONSTRUCTS, THEIR PRODUCTION AND USE |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
AU6290090A (en) | 1989-08-29 | 1991-04-08 | University Of Southampton | Bi-or trispecific (fab)3 or (fab)4 conjugates |
AU639726B2 (en) | 1989-09-08 | 1993-08-05 | Duke University | Structural alterations of the egf receptor gene in human gliomas |
US5981725A (en) | 1989-09-08 | 1999-11-09 | The Johns Hopkins Univiersity | Structural alterations of the EGF receptor gene in human tumors |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
US5273743A (en) | 1990-03-09 | 1993-12-28 | Hybritech Incorporated | Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent |
GB9012995D0 (en) | 1990-06-11 | 1990-08-01 | Celltech Ltd | Multivalent antigen-binding proteins |
US5582996A (en) | 1990-12-04 | 1996-12-10 | The Wistar Institute Of Anatomy & Biology | Bifunctional antibodies and method of preparing same |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
DE4118120A1 (en) | 1991-06-03 | 1992-12-10 | Behringwerke Ag | TETRAVALENT BISPECIFIC RECEPTORS, THEIR PRODUCTION AND USE |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
US6511663B1 (en) | 1991-06-11 | 2003-01-28 | Celltech R&D Limited | Tri- and tetra-valent monospecific antigen-binding proteins |
ATE255131T1 (en) | 1991-06-14 | 2003-12-15 | Genentech Inc | HUMANIZED HEREGULIN ANTIBODIES |
US5637481A (en) | 1993-02-01 | 1997-06-10 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5932448A (en) | 1991-11-29 | 1999-08-03 | Protein Design Labs., Inc. | Bispecific antibody heterodimers |
CA2507749C (en) | 1991-12-13 | 2010-08-24 | Xoma Corporation | Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof |
ES2102007T3 (en) | 1992-01-23 | 1997-07-16 | Merck Patent Gmbh | MONOMER AND DIMER ANTIBODY FRAGMENT FUSION PROTEINS. |
ATE503496T1 (en) | 1992-02-06 | 2011-04-15 | Novartis Vaccines & Diagnostic | BIOSYNTHETIC BINDING PROTEIN FOR TUMOR MARKERS |
GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
US5646253A (en) | 1994-03-08 | 1997-07-08 | Memorial Sloan-Kettering Cancer Center | Recombinant human anti-LK26 antibodies |
ATE165113T1 (en) | 1992-05-08 | 1998-05-15 | Creative Biomolecules Inc | MULTI-VALUE CHIMERIC PROTEINS ANALOGUE AND METHOD FOR THE APPLICATION THEREOF |
US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
PT1498427E (en) | 1992-08-21 | 2010-03-22 | Univ Bruxelles | Immunoglobulins devoid of light chains |
US5350674A (en) | 1992-09-04 | 1994-09-27 | Becton, Dickinson And Company | Intrinsic factor - horse peroxidase conjugates and a method for increasing the stability thereof |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
EP1550729B1 (en) | 1992-09-25 | 2009-05-27 | Avipep Pty Limited | Target binding polypeptide comprising an IG-like VL domain linked to an IG-like VH domain |
GB9221657D0 (en) | 1992-10-15 | 1992-11-25 | Scotgen Ltd | Recombinant bispecific antibodies |
DE69232604T2 (en) | 1992-11-04 | 2002-11-07 | City Of Hope Duarte | ANTIBODY CONSTRUCTS |
GB9323648D0 (en) | 1992-11-23 | 1994-01-05 | Zeneca Ltd | Proteins |
AU690528B2 (en) | 1992-12-04 | 1998-04-30 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
US6476198B1 (en) | 1993-07-13 | 2002-11-05 | The Scripps Research Institute | Multispecific and multivalent antigen-binding polypeptide molecules |
US5635602A (en) | 1993-08-13 | 1997-06-03 | The Regents Of The University Of California | Design and synthesis of bispecific DNA-antibody conjugates |
WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
US5786464C1 (en) | 1994-09-19 | 2012-04-24 | Gen Hospital Corp | Overexpression of mammalian and viral proteins |
EP0787185A2 (en) | 1994-10-20 | 1997-08-06 | MorphoSys AG | Targeted hetero-association of recombinant proteins to multi-functional complexes |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US6692964B1 (en) | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
CA2222055A1 (en) | 1995-05-23 | 1996-11-28 | Morphosys Gesellschaft Fur Proteinoptimierung Mbh | Multimeric proteins |
WO1997014719A1 (en) | 1995-10-16 | 1997-04-24 | Unilever N.V. | A bifunctional or bivalent antibody fragment analogue |
US6177078B1 (en) | 1995-12-29 | 2001-01-23 | Medvet Science Pty Limited | Monoclonal antibody antagonists to IL-3 |
JP2000505787A (en) | 1996-01-05 | 2000-05-16 | アメリカ合衆国 | Mesothelial antigen and method and kit for targeting it |
EP0894135B1 (en) | 1996-04-04 | 2004-08-11 | Unilever Plc | Multivalent and multispecific antigen-binding protein |
US6114148C1 (en) | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
ATE196314T1 (en) | 1996-10-25 | 2000-09-15 | Us Health | METHODS AND COMPOSITIONS FOR PREVENTING INFLAMMATION AND ANGIOGENESIS IN MAMMALS CONTAINING CD97 ALPHA SUBUNIT |
CA2288994C (en) | 1997-04-30 | 2011-07-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
US20030207346A1 (en) | 1997-05-02 | 2003-11-06 | William R. Arathoon | Method for making multispecific antibodies having heteromultimeric and common components |
ES2231991T3 (en) | 1997-06-11 | 2005-05-16 | Borean Pharma A/S | TRIMERIZATION MODULE. |
WO1998056915A2 (en) | 1997-06-12 | 1998-12-17 | Research Corporation Technologies, Inc. | Artificial antibody polypeptides |
DE69841562D1 (en) | 1997-10-27 | 2010-04-29 | Bac Ip Bv | MULTIVALENT ANTIGENBINDING PROTEINS |
EP1025230B1 (en) | 1997-12-01 | 2006-02-08 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | ANTIBODIES, INCLUDING Fv MOLECULES, AND IMMUNOCONJUGATES HAVING HIGH BINDING AFFINITY FOR MESOTHELIN AND METHODS FOR THEIR USE |
DE69922159T2 (en) | 1998-01-23 | 2005-12-01 | Vlaams Interuniversitair Instituut Voor Biotechnologie | MULTI-PURPOSE ANTIBODY DERIVATIVES |
HUP9900956A2 (en) | 1998-04-09 | 2002-04-29 | Aventis Pharma Deutschland Gmbh. | Single-chain multiple antigen-binding molecules, their preparation and use |
DE19819846B4 (en) | 1998-05-05 | 2016-11-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Multivalent antibody constructs |
GB9812545D0 (en) | 1998-06-10 | 1998-08-05 | Celltech Therapeutics Ltd | Biological products |
JP2002521053A (en) | 1998-07-28 | 2002-07-16 | マイクロメット アーゲー | Heteromini body |
US6333396B1 (en) | 1998-10-20 | 2001-12-25 | Enzon, Inc. | Method for targeted delivery of nucleic acids |
US7527787B2 (en) | 2005-10-19 | 2009-05-05 | Ibc Pharmaceuticals, Inc. | Multivalent immunoglobulin-based bioactive assemblies |
US7534866B2 (en) | 2005-10-19 | 2009-05-19 | Ibc Pharmaceuticals, Inc. | Methods and compositions for generating bioactive assemblies of increased complexity and uses |
EP1235842A4 (en) | 1999-10-15 | 2003-04-23 | Univ Massachusetts | Rna interference pathway genes as tools for targeted genetic interference |
US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
KR20030032922A (en) | 2000-02-24 | 2003-04-26 | 싸이트 테라피스 인코포레이티드 | Simultaneous stimulation and concentration of cells |
US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
ATE510855T1 (en) | 2000-03-06 | 2011-06-15 | Univ Kentucky Res Found | USE OF AN ANTIBODIES OR AN IMMUNOTOXIN THAT RESPECTIVELY THAT SELECTIVELY BINDS TO CD123 TO IMPAIR HEMATOLOGICAL CANCER PROGENIC CELLS |
NZ521540A (en) | 2000-04-11 | 2004-09-24 | Genentech Inc | Multivalent antibodies and uses therefor |
JP2004511430A (en) | 2000-05-24 | 2004-04-15 | イムクローン システムズ インコーポレイティド | Bispecific immunoglobulin-like antigen binding protein and production method |
AU2001275474A1 (en) | 2000-06-12 | 2001-12-24 | Akkadix Corporation | Materials and methods for the control of nematodes |
EP1294904A1 (en) | 2000-06-30 | 2003-03-26 | Vlaams Interuniversitair Instituut voor Biotechnologie vzw. | Heterodimeric fusion proteins |
JP2004523205A (en) | 2000-07-25 | 2004-08-05 | イムノメディクス, インコーポレイテッド | Multivalent target binding protein |
JP4261907B2 (en) | 2000-10-20 | 2009-05-13 | 中外製薬株式会社 | Low molecular weight agonist antibody |
US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
WO2002072635A2 (en) | 2001-03-13 | 2002-09-19 | University College London | Specific binding members |
CN1294148C (en) | 2001-04-11 | 2007-01-10 | 中国科学院遗传与发育生物学研究所 | Single-stranded cyctic trispecific antibody |
CA2447851C (en) | 2001-06-28 | 2012-08-28 | Domantis Limited | Dual-specific ligand and its use |
US6833441B2 (en) | 2001-08-01 | 2004-12-21 | Abmaxis, Inc. | Compositions and methods for generating chimeric heteromultimers |
ATE459651T1 (en) | 2001-08-10 | 2010-03-15 | Univ Aberdeen | ANTIGEN BINDING DOMAIN FROM FISH |
ES2276735T3 (en) | 2001-09-14 | 2007-07-01 | Affimed Therapeutics Ag | SINGLE CHAIN MULTIMERIC FV ANTIBODIES IN TANDEM. |
US20030211078A1 (en) | 2001-12-07 | 2003-11-13 | Heavner George A. | Pseudo-antibody constructs |
US7745140B2 (en) | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
CA2478011C (en) | 2002-03-01 | 2013-05-21 | Immunomedics, Inc. | Bispecific antibody point mutations for enhancing rate of clearance |
AU2003227504A1 (en) | 2002-04-15 | 2003-10-27 | Chugai Seiyaku Kabushiki Kaisha | METHOD OF CONSTRUCTING scDb LIBRARY |
US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
GB0230203D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
GB0305702D0 (en) | 2003-03-12 | 2003-04-16 | Univ Birmingham | Bispecific antibodies |
WO2004087758A2 (en) | 2003-03-26 | 2004-10-14 | Neopharm, Inc. | Il 13 receptor alpha 2 antibody and methods of use |
JP2006526408A (en) | 2003-04-22 | 2006-11-24 | アイビーシー、ファーマシューティカルズ | Multivalent protein complex |
US20050163782A1 (en) | 2003-06-27 | 2005-07-28 | Biogen Idec Ma Inc. | Modified binding molecules comprising connecting peptides |
AU2004255216B2 (en) | 2003-07-01 | 2010-08-19 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
US7696322B2 (en) | 2003-07-28 | 2010-04-13 | Catalent Pharma Solutions, Inc. | Fusion antibodies |
EP1651675A1 (en) | 2003-08-05 | 2006-05-03 | Morphotek, Inc. | A variant cell surface molecule associated with cancer |
AU2004286198C1 (en) | 2003-08-18 | 2011-02-24 | Medimmune, Llc | Humanization of antibodies |
EP1660534A2 (en) | 2003-08-22 | 2006-05-31 | MedImmune, Inc. | Humanization of antibodies |
JPWO2005035586A1 (en) | 2003-10-08 | 2007-11-22 | 協和醗酵工業株式会社 | Fusion protein composition |
US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
CA2550996A1 (en) | 2003-12-22 | 2005-07-14 | Centocor, Inc. | Methods for generating multimeric molecules |
GB0329825D0 (en) | 2003-12-23 | 2004-01-28 | Celltech R&D Ltd | Biological products |
US20050266425A1 (en) | 2003-12-31 | 2005-12-01 | Vaccinex, Inc. | Methods for producing and identifying multispecific antibodies |
US8383575B2 (en) | 2004-01-30 | 2013-02-26 | Paul Scherrer Institut | (DI)barnase-barstar complexes |
EP1765988B1 (en) | 2004-05-27 | 2017-09-20 | The Trustees of The University of Pennsylvania | Novel artificial antigen presenting cells and uses therefor |
JP2008512352A (en) | 2004-07-17 | 2008-04-24 | イムクローン システムズ インコーポレイティド | Novel tetravalent bispecific antibody |
JP2008511337A (en) | 2004-09-02 | 2008-04-17 | ジェネンテック・インコーポレーテッド | Heteromultimeric molecule |
JP4949373B2 (en) | 2005-03-10 | 2012-06-06 | モルフォテック、インク. | Anti-mesothelin antibody |
AU2006232287B2 (en) | 2005-03-31 | 2011-10-06 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing polypeptides by regulating polypeptide association |
AU2006232920B2 (en) | 2005-04-06 | 2011-09-29 | Ibc Pharmaceuticals, Inc. | Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses |
CA2605024C (en) | 2005-04-15 | 2018-05-22 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US20060263367A1 (en) | 2005-05-23 | 2006-11-23 | Fey Georg H | Bispecific antibody devoid of Fc region and method of treatment using same |
EP1726650A1 (en) | 2005-05-27 | 2006-11-29 | Universitätsklinikum Freiburg | Monoclonal antibodies and single chain antibody fragments against cell-surface prostate specific membrane antigen |
TWI323734B (en) | 2005-08-19 | 2010-04-21 | Abbott Lab | Dual variable domain immunoglobulin and uses thereof |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
DE602005018477D1 (en) | 2005-08-26 | 2010-02-04 | Pls Design Gmbh | Bivalent IgY antibody constructs for diagnostic and therapeutic applications |
WO2007044887A2 (en) | 2005-10-11 | 2007-04-19 | Transtarget, Inc. | Method for producing a population of homogenous tetravalent bispecific antibodies |
EP1962961B1 (en) | 2005-11-29 | 2013-01-09 | The University Of Sydney | Demibodies: dimerisation-activated therapeutic agents |
BRPI0707824A2 (en) | 2006-02-15 | 2011-05-10 | Imclone Systems Inc | antigen-binding protein, and methods of neutralizing tyrosine kinase receptor activation, inhibiting angiogenesis, reducing tumor growth and producing an antigen-binding protein |
GEP20135917B (en) | 2006-03-17 | 2013-09-10 | Biogen Idec Inc | Stabilized polypeptide compositions |
EP1996716B1 (en) | 2006-03-20 | 2011-05-11 | The Regents of the University of California | Engineered anti-prostate stem cell antigen (psca) antibodies for cancer targeting |
US8946391B2 (en) | 2006-03-24 | 2015-02-03 | The Regents Of The University Of California | Construction of a multivalent scFv through alkyne-azide 1,3-dipolar cycloaddition |
AR060070A1 (en) | 2006-03-24 | 2008-05-21 | Merck Patent Gmbh | HETERODYMERIC PROTEIN DOMAINS OBTAINED BY ENGINEERING |
WO2007114325A1 (en) | 2006-03-31 | 2007-10-11 | Chugai Seiyaku Kabushiki Kaisha | Antibody modification method for purifying bispecific antibody |
TWI395754B (en) | 2006-04-24 | 2013-05-11 | Amgen Inc | Humanized c-kit antibody |
WO2007137760A2 (en) | 2006-05-25 | 2007-12-06 | Bayer Schering Pharma Aktiengesellschaft | Dimeric molecular complexes |
US20070274985A1 (en) | 2006-05-26 | 2007-11-29 | Stefan Dubel | Antibody |
EP3805269A1 (en) | 2006-06-12 | 2021-04-14 | Aptevo Research and Development LLC | Single-chain multivalent binding proteins with effector function |
US8497246B2 (en) | 2006-08-18 | 2013-07-30 | Armagen Technologies, Inc. | Methods for diagnosing and treating CNS disorders by trans-blood-brain barrier delivery of protein compositions |
EP2059533B1 (en) | 2006-08-30 | 2012-11-14 | Genentech, Inc. | Multispecific antibodies |
EP2083868A2 (en) | 2006-10-04 | 2009-08-05 | Københavns Universitet | Generation of a cancer-specific immune response toward muc1 and cancer specific muc1 antibodies |
FR2906808B1 (en) | 2006-10-10 | 2012-10-05 | Univ Nantes | USE OF MONOCLONAL ANTIBODIES SPECIFIC TO THE O-ACETYLATED FORMS OF GANGLIOSIDE GD2 IN THE TREATMENT OF CERTAIN CANCERS |
KR20090105913A (en) | 2006-11-02 | 2009-10-07 | 다니엘 제이 카폰 | Hybrid immunoglobulins with moving parts |
US7635753B2 (en) | 2007-02-19 | 2009-12-22 | Wisconsin Alumni Research Foundation | Prostate cancer and melanoma antigens |
NZ614857A (en) | 2007-03-29 | 2015-04-24 | Genmab As | Bispecific antibodies and methods for production thereof |
WO2008127735A1 (en) | 2007-04-13 | 2008-10-23 | Stemline Therapeutics, Inc. | Il3ralpha antibody conjugates and uses thereof |
CA2682605A1 (en) | 2007-04-18 | 2008-10-30 | Zymogenetics, Inc. | Single chain fc, methods of making and methods of treatment |
JP2010190572A (en) | 2007-06-01 | 2010-09-02 | Sapporo Medical Univ | Antibody directed against il13ra2, and diagnostic/therapeutic agent comprising the antibody |
EP2626371A1 (en) | 2007-07-31 | 2013-08-14 | MedImmune, LLC | Multispecific epitope binding proteins and uses thereof |
JP5485152B2 (en) | 2007-08-15 | 2014-05-07 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Monospecific and multispecific antibodies and methods of use |
KR101554848B1 (en) | 2007-10-01 | 2015-09-21 | 브리스톨-마이어스 스큅 컴퍼니 | Human antibodies that bind mesothelin, and uses thereof |
NZ585551A (en) | 2007-11-26 | 2012-06-29 | Bayer Schering Pharma Ag | Anti-mesothelin antibodies and uses therefor |
WO2009068625A2 (en) | 2007-11-27 | 2009-06-04 | Ablynx N.V. | Amino acid sequences directed against her2 and polypeptides comprising the same for the treatment of cancers and/or tumors |
BRPI0819693A2 (en) | 2007-11-30 | 2020-08-18 | Glaxo Group Limited | CONSTRUCTION OF ANTIGEN BINDING, METHOD FOR TREATING A PATIENT SUFFERING FROM CANCER OR AN INFLAMMATORY DISEASE, POLYNUCLEOTIDE SEQUENCE, POLYNUCLEOTIDE, HOSTED CELL, TRANSFORMED, EFFECTIVENESS, HUMAN RESOURCE |
US8242247B2 (en) | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
US8227577B2 (en) | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
ES2563027T3 (en) | 2008-01-07 | 2016-03-10 | Amgen Inc. | Method for manufacturing antibody Fc heterodimer molecules using electrostatic conduction effects |
CN102459342B (en) | 2009-04-27 | 2015-01-07 | 协和发酵麒麟株式会社 | Anti-il-3ra antibody for use in treatment of blood tumor |
CN102459346B (en) | 2009-04-27 | 2016-10-26 | 昂考梅德药品有限公司 | The method manufacturing heteromultimers molecule |
AU2010315243B2 (en) | 2009-11-03 | 2016-08-25 | City Of Hope | Truncated epidermal growth factor receptor (EGFRt) for transduced T cell selection |
WO2011069019A2 (en) | 2009-12-02 | 2011-06-09 | David Ho | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use |
SG10201501342UA (en) | 2010-02-24 | 2015-04-29 | Immunogen Inc | Folate receptor 1 antibodies and immunoconjugates and uses thereof |
CN110066339A (en) | 2010-04-20 | 2019-07-30 | 根马布股份公司 | Albumen of the FC containing heterodimeric antibodies and preparation method thereof |
US9242014B2 (en) | 2010-06-15 | 2016-01-26 | The Regents Of The University Of California | Receptor tyrosine kinase-like orphan receptor 1 (ROR1) single chain Fv antibody fragment conjugates and methods of use thereof |
ES2961381T3 (en) | 2010-06-19 | 2024-03-11 | Memorial Sloan Kettering Cancer Center | Anti-GD2 antibodies |
EP2614143B1 (en) | 2010-09-08 | 2018-11-07 | Baylor College Of Medicine | Immunotherapy of non-small lung cancer using genetically engineered gd2-specific t cells |
MX347078B (en) | 2010-12-09 | 2017-04-10 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer. |
TR201815488T4 (en) | 2011-04-08 | 2018-11-21 | Health | Use of anti-epidermal growth factor receptor variant III for chimeric antigen receptors and cancer treatment. |
AR086044A1 (en) | 2011-05-12 | 2013-11-13 | Imclone Llc | ANTIBODIES THAT SPECIFICALLY JOIN A C-KIT EXTRACELLULAR DOMAIN AND USES OF THE SAME |
RS64791B1 (en) | 2011-05-27 | 2023-11-30 | Glaxo Group Ltd | Bcma (cd269/tnfrsf17) - binding proteins |
EP3326467B1 (en) | 2011-09-16 | 2020-03-11 | Baylor College of Medicine | Targeting the tumor microenvironment using manipulated nkt cells |
MX2014003176A (en) | 2011-09-16 | 2015-08-05 | Univ Pennsylvania | Rna engineered t cells for the treatment of cancer. |
ITMO20110270A1 (en) | 2011-10-25 | 2013-04-26 | Sara Caldrer | A MODELED EFFECTIVE CELL FOR THE TREATMENT OF NEOPLASIES EXPRESSING THE DISIALONGANGLIOSIDE GD2 |
CN110964115B (en) | 2011-10-27 | 2024-03-12 | 健玛保 | Production of heterodimeric proteins |
US9272002B2 (en) | 2011-10-28 | 2016-03-01 | The Trustees Of The University Of Pennsylvania | Fully human, anti-mesothelin specific chimeric immune receptor for redirected mesothelin-expressing cell targeting |
WO2013074916A1 (en) | 2011-11-18 | 2013-05-23 | Board Of Regents, The University Of Texas System | Car+ t cells genetically modified to eliminate expression of t- cell receptor and/or hla |
US9439768B2 (en) | 2011-12-08 | 2016-09-13 | Imds Llc | Glenoid vault fixation |
JP6850528B2 (en) | 2012-02-13 | 2021-03-31 | シアトル チルドレンズ ホスピタル ドゥーイング ビジネス アズ シアトル チルドレンズ リサーチ インスティテュート | Bispecific chimeric antigen receptor and its therapeutic use |
SG11201404285VA (en) | 2012-02-22 | 2014-10-30 | Univ Pennsylvania | Compositions and methods for generating a persisting population of t cells useful for the treatment of cancer |
CA3116051C (en) | 2012-03-23 | 2023-09-26 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-mesothelin chimeric antigen receptors |
WO2013151649A1 (en) | 2012-04-04 | 2013-10-10 | Sialix Inc | Glycan-interacting compounds |
HUE059815T2 (en) | 2012-05-18 | 2022-12-28 | Aptevo Res & Development Llc | Bispecific scfv immunofusion (bif) binding to cd123 and cd3 |
WO2013192294A1 (en) | 2012-06-20 | 2013-12-27 | Boston 3T Biotechnologies, Inc. | Cellular therapies for treating and preventing cancers and other immune system disorders |
ES2778701T3 (en) * | 2012-07-13 | 2020-08-11 | The Trustees Of The Univ Of Pennsylvania Center For Technology Transfer | Management of toxicity for antitumor activity of CAR |
SG10201701339RA (en) | 2012-08-20 | 2017-03-30 | Seattle Children S Hospital Dba Seattle Children S Res Inst | Method and compositions for cellular immunotherapy |
US9365641B2 (en) | 2012-10-01 | 2016-06-14 | The Trustees Of The University Of Pennsylvania | Compositions and methods for targeting stromal cells for the treatment of cancer |
US10117896B2 (en) | 2012-10-05 | 2018-11-06 | The Trustees Of The University Of Pennsylvania | Use of a trans-signaling approach in chimeric antigen receptors |
TW201425336A (en) | 2012-12-07 | 2014-07-01 | Amgen Inc | BCMA antigen binding proteins |
WO2014122143A1 (en) | 2013-02-05 | 2014-08-14 | Engmab Ag | Method for the selection of antibodies against bcma |
WO2014130635A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
EP3626741A1 (en) | 2013-02-20 | 2020-03-25 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
WO2014138819A1 (en) | 2013-03-14 | 2014-09-18 | Csl Limited | Agents that neutralize il-3 signaling and uses thereof |
US20160031996A1 (en) | 2013-03-14 | 2016-02-04 | Csl Limited | Anti il-3r alpha agents and uses thereof |
US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
EP3623380A1 (en) | 2013-03-15 | 2020-03-18 | Michael C. Milone | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
AR095374A1 (en) | 2013-03-15 | 2015-10-14 | Amgen Res (Munich) Gmbh | UNION MOLECULES FOR BCMA AND CD3 |
US9446105B2 (en) * | 2013-03-15 | 2016-09-20 | The Trustees Of The University Of Pennsylvania | Chimeric antigen receptor specific for folate receptor β |
UY35468A (en) | 2013-03-16 | 2014-10-31 | Novartis Ag | CANCER TREATMENT USING AN ANTI-CD19 CHEMERIC ANTIGEN RECEIVER |
JP6546160B2 (en) * | 2013-06-10 | 2019-07-17 | デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド | Methods and compositions for reducing immunosuppression by tumor cells |
RU2714902C2 (en) | 2013-12-19 | 2020-02-20 | Новартис Аг | Chimeric human mesotheliogen antigen receptors and use thereof |
US10287354B2 (en) | 2013-12-20 | 2019-05-14 | Novartis Ag | Regulatable chimeric antigen receptor |
EP3119423B1 (en) | 2014-03-15 | 2022-12-14 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
SG11201700418VA (en) | 2014-07-21 | 2017-02-27 | Novartis Ag | Treatment of cancer using a cll-1 chimeric antigen receptor |
MX2017001011A (en) | 2014-07-21 | 2018-05-28 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor. |
EP3172234B1 (en) | 2014-07-21 | 2020-04-08 | Novartis AG | Treatment of cancer using a cd33 chimeric antigen receptor |
EP3172231B1 (en) | 2014-07-24 | 2021-05-05 | Bluebird Bio, Inc. | Bcma chimeric antigen receptors |
TW202140557A (en) * | 2014-08-19 | 2021-11-01 | 瑞士商諾華公司 | Treatment of cancer using a cd123 chimeric antigen receptor |
-
2017
- 2017-08-01 RU RU2019105693A patent/RU2019105693A/en unknown
- 2017-08-01 CA CA3032581A patent/CA3032581A1/en active Pending
- 2017-08-01 WO PCT/US2017/044909 patent/WO2018026819A2/en unknown
- 2017-08-01 BR BR112019002035-7A patent/BR112019002035A2/en not_active Application Discontinuation
- 2017-08-01 EP EP17755330.2A patent/EP3490590A2/en active Pending
- 2017-08-01 US US16/322,285 patent/US20190161542A1/en not_active Abandoned
- 2017-08-01 KR KR1020197006125A patent/KR20190036551A/en not_active Application Discontinuation
- 2017-08-01 CN CN201780057831.4A patent/CN110267677A/en active Pending
- 2017-08-01 MX MX2019001469A patent/MX2019001469A/en unknown
- 2017-08-01 AU AU2017306267A patent/AU2017306267A1/en not_active Abandoned
- 2017-08-01 JP JP2019505190A patent/JP2019527696A/en not_active Withdrawn
- 2017-08-01 SG SG11201900885VA patent/SG11201900885VA/en unknown
-
2019
- 2019-01-31 IL IL264588A patent/IL264588A/en unknown
-
2022
- 2022-01-12 JP JP2022003134A patent/JP2022062040A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
AU2017306267A1 (en) | 2019-02-14 |
JP2019527696A (en) | 2019-10-03 |
EP3490590A2 (en) | 2019-06-05 |
BR112019002035A2 (en) | 2019-05-14 |
WO2018026819A2 (en) | 2018-02-08 |
RU2019105693A3 (en) | 2021-04-26 |
RU2019105693A (en) | 2020-09-01 |
KR20190036551A (en) | 2019-04-04 |
CA3032581A1 (en) | 2018-02-08 |
IL264588A (en) | 2019-02-28 |
WO2018026819A3 (en) | 2018-03-08 |
JP2022062040A (en) | 2022-04-19 |
US20190161542A1 (en) | 2019-05-30 |
MX2019001469A (en) | 2019-10-02 |
CN110267677A (en) | 2019-09-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SG11201900885VA (en) | Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule | |
SG11201908719QA (en) | Biomarkers and car t cell therapies with enhanced efficacy | |
SG11201900344YA (en) | Treatment and prevention of cytokine release syndrome using a chimeric antigen receptor in combination with a kinase inhibitor | |
SG11201807489PA (en) | Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore | |
SG11201811432WA (en) | Rna for cancer therapy | |
SG11201907753TA (en) | Bispecific binding molecules that are capable of binding cd137 and tumor antigens, and uses thereof | |
SG11201808990QA (en) | Compositions for topical application of compounds | |
SG11201909154SA (en) | Bispecific antibodies specifically binding to pd1 and lag3 | |
SG11201407580YA (en) | Composition comprising two antibodies engineered to have reduced and increased effector function | |
SG11201810420YA (en) | Antibodies to alpha-synuclein and uses thereof | |
SG11201910143TA (en) | Combination of a cell therapy and an immunomodulatory compound | |
SG11201900677SA (en) | Combination therapies of chimeric antigen receptors adn pd-1 inhibitors | |
SG11201809344QA (en) | Process for synthesizing 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)-pyridin-3-yl)methoxy)benzaldehyde | |
SG11201906192SA (en) | Methods of treating cancer with anti-pd-1 antibodies | |
SG11201909656YA (en) | Intracellular kinase associated with resistance against anti-tumour immune responses, and uses thereof | |
SG11201805044WA (en) | Compounds useful as kinase inhibitors | |
SG11201908784TA (en) | Improved antigen binding receptor formats | |
SG11201803956UA (en) | Anti-dr5 antibodies and methods of use thereof | |
SG11201808222RA (en) | Methods of treatment of cholestatic diseases | |
SG11201908325PA (en) | Process for the preparation of glucuronide drug-linkers and intermediates thereof | |
SG11201907364WA (en) | Anti-tryptase antibodies, compositions thereof, and uses thereof | |
SG11201805149XA (en) | Compositions comprising 15-hepe and methods of using the same | |
SG11201909064RA (en) | Combination of an anti-pd-l1 antibody and a dna-pk inhibitor for the treatment of cancer | |
SG11201810642XA (en) | Aldose reductase inhibitors and methods of use thereof | |
SG11202000333UA (en) | Bicyclic ketone compounds and methods of use thereof |