JP6916776B2 - Ａｎｇ−２に対する重鎖のみ抗体 - Google Patents
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- JP6916776B2 JP6916776B2 JP2018504124A JP2018504124A JP6916776B2 JP 6916776 B2 JP6916776 B2 JP 6916776B2 JP 2018504124 A JP2018504124 A JP 2018504124A JP 2018504124 A JP2018504124 A JP 2018504124A JP 6916776 B2 JP6916776 B2 JP 6916776B2
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Ophthalmology & Optometry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562198518P | 2015-07-29 | 2015-07-29 | |
| US62/198,518 | 2015-07-29 | ||
| US201562205185P | 2015-08-14 | 2015-08-14 | |
| US62/205,185 | 2015-08-14 | ||
| PCT/US2016/044838 WO2017020001A2 (en) | 2015-07-29 | 2016-07-29 | Heavy chain only antibodies to ang-2 |
Publications (3)
| Publication Number | Publication Date |
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| JP2018527327A JP2018527327A (ja) | 2018-09-20 |
| JP2018527327A5 JP2018527327A5 (cg-RX-API-DMAC7.html) | 2019-07-18 |
| JP6916776B2 true JP6916776B2 (ja) | 2021-08-11 |
Family
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| US12478503B2 (en) | 2009-05-18 | 2025-11-25 | Glaukos Corporation | Implants with controlled drug delivery features and methods of using same |
| HUE051165T2 (hu) * | 2015-07-29 | 2021-03-01 | Allergan Inc | ANG-2 elleni, csak nehézláncot tartalmazó antitestek |
| JP2018523673A (ja) * | 2015-08-14 | 2018-08-23 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Ｐｄｇｆに対する重鎖のみ抗体 |
| US20220185875A1 (en) * | 2019-03-18 | 2022-06-16 | Jiangsu Hengrui Medicine Co., Ltd. | Bispecific antibody specifically bound to vegf and ang2 |
| KR20230098637A (ko) * | 2020-11-04 | 2023-07-04 | 페이트 세러퓨틱스, 인코포레이티드 | 이종성 종양 제어를 위한 조작된 iPSC 및 면역 효과기 세포 |
| CN116003591B (zh) * | 2022-12-12 | 2023-09-19 | 三门峡市眼科医院 | Ang-2抗体及其应用 |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| DE68925971T2 (de) | 1988-09-23 | 1996-09-05 | Cetus Oncology Corp | Zellenzuchtmedium für erhöhtes zellenwachstum, zur erhöhung der langlebigkeit und expression der produkte |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| US6797492B2 (en) | 1991-05-17 | 2004-09-28 | Merck & Co., Inc. | Method for reducing the immunogenicity of antibody variable domains |
| US5534615A (en) | 1994-04-25 | 1996-07-09 | Genentech, Inc. | Cardiac hypertrophy factor and uses therefor |
| US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
| ATE293640T1 (de) | 1997-04-07 | 2005-05-15 | Genentech Inc | Anti-vegf antikörper |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| US7117096B2 (en) | 2001-04-17 | 2006-10-03 | Abmaxis, Inc. | Structure-based selection and affinity maturation of antibody library |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| CN1301692C (zh) | 2002-09-18 | 2007-02-28 | 阿勒根公司 | 眼植入物导入的器械 |
| GB0230203D0 (en) * | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
| US7758859B2 (en) | 2003-08-01 | 2010-07-20 | Genentech, Inc. | Anti-VEGF antibodies |
| US20050282233A1 (en) | 2004-03-05 | 2005-12-22 | Ludwig Institute For Cancer Research | Multivalent antibody materials and methods for VEGF/PDGF family of growth factors |
| ES2440990T5 (es) | 2004-07-22 | 2022-10-25 | Univ Erasmus Med Ct Rotterdam | Moléculas de unión |
| EP1819355A4 (en) * | 2004-09-28 | 2009-08-12 | Genexel Sein Inc | METHOD OF USE OF A CHIMERIC COILED COIL MOLECULE |
| CN101128483B (zh) * | 2004-12-21 | 2015-06-03 | 阿斯利康公司 | 血管生成素-2的抗体及其应用 |
| JP5184374B2 (ja) | 2006-01-25 | 2013-04-17 | エラスムス・ユニヴァーシティ・メディカル・センター・ロッテルダム | 対立遺伝子排除 |
| TWI468417B (zh) | 2007-11-30 | 2015-01-11 | Genentech Inc | 抗－ｖｅｇｆ抗體 |
| US8268314B2 (en) * | 2008-10-08 | 2012-09-18 | Hoffmann-La Roche Inc. | Bispecific anti-VEGF/anti-ANG-2 antibodies |
| CN102307902B (zh) * | 2008-12-10 | 2016-02-24 | 埃博灵克斯股份有限公司 | 用于治疗与血管发生相关的疾病和病症的针对血管生成素/Tie系统的氨基酸序列和包括其的多肽 |
| GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
| AR080794A1 (es) | 2010-03-26 | 2012-05-09 | Hoffmann La Roche | Anticuerpos bivalentes biespecificos anti- vegf/ anti-ang-2 |
| US9527925B2 (en) * | 2011-04-01 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Bispecific binding molecules binding to VEGF and ANG2 |
| HUE044263T2 (hu) * | 2012-03-30 | 2019-10-28 | Boehringer Ingelheim Int | ANG2-kötõ molekulák |
| RU2639287C2 (ru) * | 2012-06-27 | 2017-12-20 | Ф. Хоффманн-Ля Рош Аг | Способ отбора и получения высокоселективных и мультиспецифичных нацеливающих групп с заданными свойствами, включающих по меньшей мере две различные связывающие группировки, и их применения |
| RS57704B1 (sr) | 2012-07-13 | 2018-12-31 | Roche Glycart Ag | Bispecifična anti-vegf/anti-ang-2 antitela i njihova primena u lečenju vaskularnih bolesti oka |
| WO2014072876A1 (en) | 2012-11-09 | 2014-05-15 | Pfizer Inc. | Platelet-derived growth factor b specific antibodies and compositions and uses thereof |
| JO3405B1 (ar) | 2013-01-09 | 2019-10-20 | Regeneron Pharma | الأجسام المضادة لمضاد مستقبل عامل النمو المشتق من الصفائح الدموية - بيتا واستخداماتها |
| US10993420B2 (en) | 2013-03-15 | 2021-05-04 | Erasmus University Medical Center | Production of heavy chain only antibodies in transgenic mammals |
| EP2832746B1 (en) * | 2013-07-29 | 2018-07-18 | Samsung Electronics Co., Ltd | Anti-Ang2 antibody |
| KR102146845B1 (ko) * | 2013-07-30 | 2020-08-21 | 삼성전자주식회사 | 앤지오포이에틴-2에 특이적으로 결합하는 항체 및 그의 용도 |
| MX2017005975A (es) * | 2014-11-10 | 2017-06-29 | Hoffmann La Roche | Anticuerpos anti factor de crecimiento derivado de plaquetas b (pdgf-b) y metodos de uso. |
| HUE051165T2 (hu) * | 2015-07-29 | 2021-03-01 | Allergan Inc | ANG-2 elleni, csak nehézláncot tartalmazó antitestek |
| JP2018523673A (ja) * | 2015-08-14 | 2018-08-23 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Ｐｄｇｆに対する重鎖のみ抗体 |
-
2016
- 2016-07-29 HU HUE16748025A patent/HUE051165T2/hu unknown
- 2016-07-29 DK DK16748025.0T patent/DK3328886T3/da active
- 2016-07-29 BR BR112018001762A patent/BR112018001762A2/pt not_active IP Right Cessation
- 2016-07-29 PL PL16748025T patent/PL3328886T3/pl unknown
- 2016-07-29 JP JP2018504124A patent/JP6916776B2/ja not_active Expired - Fee Related
- 2016-07-29 CN CN201680044324.2A patent/CN107849126B/zh not_active Expired - Fee Related
- 2016-07-29 AU AU2016298398A patent/AU2016298398A1/en not_active Abandoned
- 2016-07-29 US US15/223,855 patent/US10266589B2/en active Active
- 2016-07-29 ES ES16748025T patent/ES2828694T3/es active Active
- 2016-07-29 EP EP16748025.0A patent/EP3328886B1/en active Active
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- 2016-07-29 WO PCT/US2016/044838 patent/WO2017020001A2/en not_active Ceased
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- 2016-07-29 CA CA2992660A patent/CA2992660A1/en active Pending
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2019
- 2019-04-16 US US16/385,384 patent/US11046756B2/en not_active Expired - Fee Related
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2021
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2022
- 2022-10-26 AU AU2022259761A patent/AU2022259761A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018527327A (ja) | 2018-09-20 |
| US20190248882A1 (en) | 2019-08-15 |
| EP3792279A2 (en) | 2021-03-17 |
| PL3328886T3 (pl) | 2021-02-08 |
| DK3328886T3 (da) | 2020-11-02 |
| EP3792279A3 (en) | 2021-07-07 |
| EP3328886B1 (en) | 2020-09-16 |
| AU2016298398A1 (en) | 2018-02-08 |
| WO2017020001A3 (en) | 2017-03-16 |
| ES2828694T3 (es) | 2021-05-27 |
| EP3328886A2 (en) | 2018-06-06 |
| CN107849126A (zh) | 2018-03-27 |
| HUE051165T2 (hu) | 2021-03-01 |
| AU2022259761A1 (en) | 2022-12-01 |
| CN107849126B (zh) | 2022-04-08 |
| US11046756B2 (en) | 2021-06-29 |
| CA2992660A1 (en) | 2017-02-02 |
| RU2018103960A3 (cg-RX-API-DMAC7.html) | 2020-01-16 |
| BR112018001762A2 (pt) | 2018-09-18 |
| US20170107279A1 (en) | 2017-04-20 |
| US20210324064A1 (en) | 2021-10-21 |
| RU2749674C2 (ru) | 2021-06-16 |
| HK1253947A1 (en) | 2019-07-05 |
| RU2018103960A (ru) | 2019-08-28 |
| US10266589B2 (en) | 2019-04-23 |
| WO2017020001A2 (en) | 2017-02-02 |
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