CA3010685A1 - Bispecific t cell engaging antibody constructs - Google Patents
Bispecific t cell engaging antibody constructs Download PDFInfo
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- CA3010685A1 CA3010685A1 CA3010685A CA3010685A CA3010685A1 CA 3010685 A1 CA3010685 A1 CA 3010685A1 CA 3010685 A CA3010685 A CA 3010685A CA 3010685 A CA3010685 A CA 3010685A CA 3010685 A1 CA3010685 A1 CA 3010685A1
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Classifications
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- C07K—PEPTIDES
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- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Families Citing this family (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008234020B2 (en) * | 2007-04-03 | 2013-02-07 | Amgen Research (Munich) Gmbh | Cross-species-specific CD3-epsilon binding domain |
| CA2738568C (en) | 2008-10-01 | 2024-02-20 | Micromet Ag | Cross-species-specific single domain bispecific single chain antibody |
| PL2686347T3 (pl) | 2011-03-16 | 2018-10-31 | Argenx Bvba | Przeciwciała przeciwko CD70 |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對ｂｃｍａ之e3以及ｃｄ３的結合分子 |
| JO3519B1 (ar) | 2013-01-25 | 2020-07-05 | Amgen Inc | تركيبات أجسام مضادة لأجل cdh19 و cd3 |
| MX377344B (es) | 2014-07-31 | 2025-03-07 | Amgen Res Munich Gmbh | Constructos de anticuerpos de cadena sencilla biespecífica específicos para especies cruzadas optimizadas. |
| US10391168B1 (en) | 2014-08-22 | 2019-08-27 | University Of Bern | Anti-CD70 combination therapy |
| TWI717375B (zh) | 2015-07-31 | 2021-02-01 | 德商安美基研究（慕尼黑）公司 | Ｃｄ７０及ｃｄ３抗體構築體 |
| EA039859B1 (ru) * | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究（慕尼黑）公司 | Egfrviii及cd3抗體構築體 |
| TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究（慕尼黑）公司 | Ｆｌｔ３及ｃｄ３抗體構築體 |
| TWI796283B (zh) * | 2015-07-31 | 2023-03-21 | 德商安美基研究（慕尼黑）公司 | Ｍｓｌｎ及ｃｄ３抗體構築體 |
| TW202346349A (zh) * | 2015-07-31 | 2023-12-01 | 德商安美基研究（慕尼黑）公司 | Dll3及cd3抗體構築體 |
| CN116063544A (zh) | 2016-02-03 | 2023-05-05 | 安进研发（慕尼黑）股份有限公司 | Bcma和cd3双特异性t细胞接合抗体构建体 |
| CN114716557A (zh) | 2016-02-03 | 2022-07-08 | 安进研发（慕尼黑）股份有限公司 | Psma和cd3双特异性t细胞接合抗体构建体 |
| JOP20190189A1 (ar) * | 2017-02-02 | 2019-08-01 | Amgen Res Munich Gmbh | تركيبة صيدلانية ذات درجة حموضة منخفضة تتضمن بنيات جسم مضاد يستهدف الخلية t |
| EP3619235A1 (en) | 2017-04-11 | 2020-03-11 | Inhibrx, Inc. | Multispecific polypeptide constructs having constrained cd3 binding and methods of using the same |
| CA3070446A1 (en) | 2017-07-25 | 2019-01-31 | Immutics, Inc. | Treating cancer by blocking the interaction of tim-3 and its ligand |
| ES2975221T3 (es) | 2017-08-03 | 2024-07-04 | Amgen Inc | Muteínas de interleucina-21 y métodos de tratamiento |
| CN116003405A (zh) | 2017-09-08 | 2023-04-25 | 美国安进公司 | Kras g12c的抑制剂及其使用方法 |
| BR112020007309A2 (pt) | 2017-10-14 | 2020-09-29 | Cytomx Therapeutics, Inc. | anticorpos, anticorpos ativáveis, anticorpos biespecíficos e anticorpos ativáveis biespecíficos e métodos de uso dos mesmos |
| JP2021500930A (ja) | 2017-11-01 | 2021-01-14 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｃｏｍｐボディ−多価標的結合物質 |
| WO2019118426A1 (en) | 2017-12-11 | 2019-06-20 | Amgen Inc. | Continuous manufacturing process for bispecific antibody products |
| CN111655729B (zh) | 2017-12-19 | 2023-10-20 | 瑟罗泽恩奥普瑞汀公司 | 抗卷曲蛋白抗体和使用方法 |
| WO2019126398A1 (en) | 2017-12-19 | 2019-06-27 | Surrozen, Inc. | Wnt surrogate molecules and uses thereof |
| AU2018393076B2 (en) | 2017-12-19 | 2025-11-20 | Surrozen Operating, Inc. | Anti-LRP5/6 antibodies and methods of use |
| TW201940518A (zh) * | 2017-12-29 | 2019-10-16 | 美商安進公司 | 針對ｍｕｃ１７和ｃｄ３之雙特異性抗體構建體 |
| WO2019139987A1 (en) | 2018-01-09 | 2019-07-18 | Elstar Therapeutics, Inc. | Calreticulin binding constructs and engineered t cells for the treatment of diseases |
| JOP20200172A1 (ar) | 2018-01-12 | 2020-07-12 | Amgen Inc | الأجسام المضادة لـ pd-1 وطرق العلاج |
| GB201800649D0 (en) | 2018-01-16 | 2018-02-28 | Argenx Bvba | CD70 Combination Therapy |
| PE20211299A1 (es) | 2018-02-01 | 2021-07-20 | Pfizer | Receptores de antigeno quimericos dirigidos a cd70 |
| CA3090032A1 (en) * | 2018-02-01 | 2019-08-08 | Pfizer Inc. | Antibodies specific for cd70 and their uses |
| SG11202009804RA (en) | 2018-04-11 | 2020-11-27 | Inhibrx Inc | Multispecific polypeptide constructs having constrained cd3 binding and related methods and uses |
| AU2019250882B2 (en) | 2018-04-12 | 2025-10-16 | Amgen Inc. | Methods for making stable protein compositions |
| CN112955465A (zh) | 2018-07-03 | 2021-06-11 | 马伦戈治疗公司 | 抗tcr抗体分子及其用途 |
| CN112566940B (zh) * | 2018-07-05 | 2025-06-13 | 瑟罗泽恩奥普瑞汀公司 | 多特异性wnt替代分子和其用途 |
| TW202035451A (zh) | 2018-07-24 | 2020-10-01 | 美商英伊布里克斯公司 | 含有受限cd3結合域及受體結合區之多重特異性多肽構築體及其使用方法 |
| AU2019313444A1 (en) * | 2018-07-30 | 2021-02-18 | Amgen Inc. | Prolonged administration of a bispecific antibody construct binding to CD33 and CD3 |
| CA3112655A1 (en) * | 2018-10-01 | 2020-04-09 | Amgen Inc. | Methods for reducing aggregation of bispecific antibodies |
| CA3115089A1 (en) * | 2018-10-11 | 2020-04-16 | Inhibrx, Inc. | Dll3 single domain antibodies and therapeutic compositions thereof |
| MX2021003976A (es) | 2018-10-11 | 2021-05-27 | Amgen Inc | Procesamiento posterior de constructos de anticuerpos biespecificos. |
| TWI844570B (zh) | 2018-10-23 | 2024-06-11 | 美商安進公司 | 用於即時預測的拉曼光譜模型之自動校準及自動維護 |
| WO2020094834A1 (en) * | 2018-11-09 | 2020-05-14 | Euchloe Bio Pte. Ltd. | Il2rbeta/common gamma chain antibodies |
| TWI848030B (zh) | 2018-12-18 | 2024-07-11 | 比利時商阿根思公司 | Ｃｄ７０組合治療 |
| TWI871300B (zh) * | 2019-01-28 | 2025-02-01 | 美商安進公司 | 藉由將藥物物質和藥物產品過程整體化的生物製劑製造之連續製造過程 |
| CN120058944A (zh) | 2019-01-30 | 2025-05-30 | 真和制药有限公司 | 抗gal3抗体及其用途 |
| CN119039441A (zh) | 2019-02-21 | 2024-11-29 | 马伦戈治疗公司 | 与nkp30结合的抗体分子及其用途 |
| CN114026122B (zh) | 2019-02-21 | 2024-12-31 | 马伦戈治疗公司 | 结合t细胞相关癌细胞的多功能分子及其用途 |
| CN114341176A (zh) * | 2019-04-08 | 2022-04-12 | 纪念斯隆凯特琳癌症中心 | Cd19抗体及其使用方法 |
| WO2020247852A1 (en) * | 2019-06-07 | 2020-12-10 | Amgen Inc. | Bispecific binding constructs |
| CA3137494A1 (en) | 2019-06-13 | 2020-12-17 | Amgen Inc. | Automated biomass-based perfusion control in the manufacturing of biologics |
| US20210102002A1 (en) | 2019-08-06 | 2021-04-08 | Xencor, Inc. | HETERODIMERIC IgG-LIKE BISPECIFIC ANTIBODIES |
| MX2022002981A (es) | 2019-09-10 | 2022-04-06 | Amgen Inc | Metodo de purificacion para polipeptidos de union a antigeno biespecificos con capacidad de union dinamica de captura de proteina l mejorada. |
| US12000915B2 (en) | 2019-10-03 | 2024-06-04 | Amgen Inc. | Method for conducting solid state NMR on macromolecule-containing solid state formulations |
| WO2021081326A1 (en) * | 2019-10-25 | 2021-04-29 | Amgen Inc. | Compositions and methods for minimizing protein loss at low protein concentrations |
| WO2021091906A1 (en) | 2019-11-04 | 2021-05-14 | Amgen Inc. | Methods for treating leukemia |
| AU2020377483A1 (en) * | 2019-11-06 | 2022-05-26 | Amgen Inc. | Multitargeting antigen-binding molecules for use in proliferative diseases |
| PT3819007T (pt) | 2019-11-11 | 2024-09-20 | Amgen Inc | Regime de dosagem para agentes anti-bcma |
| CA3156683A1 (en) * | 2019-11-13 | 2021-05-20 | Amgen Inc. | METHOD FOR REDUCING AGGREGATE FORMATION IN DOWNSTREAM PROCESSING OF BI-SPECIFIC ANTIGEN-BINDING MOLECULES |
| EP4069298A4 (en) * | 2019-12-05 | 2024-01-03 | Arbele Limited | COMPOSITION OF TRIAXIAL ANTIBODIES AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| GB201918230D0 (en) | 2019-12-11 | 2020-01-22 | Prec Therapeutics Ltd | Antibodies and their uses |
| CN116234829A (zh) | 2020-01-03 | 2023-06-06 | 马伦戈治疗公司 | 抗tcr抗体分子及其用途 |
| US20230093169A1 (en) * | 2020-01-22 | 2023-03-23 | Amgen Research (Munch) Gmbh | Combinations of antibody constructs and inhibitors of cytokine release syndrome and uses thereof |
| BR112022014667A2 (pt) | 2020-01-29 | 2022-09-20 | Inhibrx Inc | Anticorpos de domínio único de cd28 e construtos multivalentes e multiespecíficos dos mesmos |
| WO2021158469A1 (en) | 2020-02-03 | 2021-08-12 | Amgen Inc. | Multivariate bracketing approach for sterile filter validation |
| CN115916963A (zh) | 2020-03-27 | 2023-04-04 | 门德斯有限公司 | 白血病来源的经修饰细胞用于增强过继性细胞治疗的效力的离体用途 |
| EP4157338A4 (en) | 2020-05-26 | 2024-11-13 | TrueBinding, Inc. | METHOD FOR TREATING INFLAMMATORY DISEASES BY GALECTIN-3 BLOCKING |
| KR20230033647A (ko) | 2020-06-30 | 2023-03-08 | 멘두스 비.브이. | 난소암 백신에서 백혈병 유래 세포의 용도 |
| WO2022060878A1 (en) | 2020-09-16 | 2022-03-24 | Amgen Inc. | Methods for treating prostate cancer |
| WO2022060901A1 (en) | 2020-09-16 | 2022-03-24 | Amgen Inc. | Methods for administering therapeutic doses of bispecific t-cell engaging molecules for the treatment of cancer |
| CA3187272A1 (en) | 2020-10-08 | 2022-04-14 | Thorsten Ross | Trispecific binders |
| US20220168407A1 (en) | 2020-11-05 | 2022-06-02 | Dcprime B.V. | Use of tumor-independent antigens in immunotherapies |
| JP2023549116A (ja) | 2020-11-06 | 2023-11-22 | アムジエン・インコーポレーテツド | 選択性が増大した多標的二重特異性抗原結合分子 |
| TW202233682A (zh) | 2020-11-10 | 2022-09-01 | 美商安進公司 | 用於投與ＢＣＭＡｘＣＤ３結合分子之方法 |
| WO2022140797A1 (en) | 2020-12-23 | 2022-06-30 | Immunowake Inc. | Immunocytokines and uses thereof |
| CA3204628A1 (en) * | 2021-01-13 | 2022-07-21 | John T. POIRIER | Antibody-pyrrolobenzodiazepine derivative conjugate |
| TW202245844A (zh) * | 2021-01-13 | 2022-12-01 | 紀念斯隆凱特琳癌症中心 | 抗dll3抗體-藥物結合物 |
| EP4281102A1 (en) | 2021-01-22 | 2023-11-29 | Mendus B.V. | Methods of tumor vaccination |
| US20240075406A1 (en) | 2021-03-10 | 2024-03-07 | Amgen Inc. | Parallel chromatography systems and methods |
| JP2024509877A (ja) | 2021-03-10 | 2024-03-05 | アムジエン・インコーポレーテツド | 組換えタンパク質の精製方法 |
| AU2022232951B2 (en) | 2021-03-10 | 2025-06-26 | Immunowake Inc. | Immunomodulatory molecules and uses thereof |
| JP2024518369A (ja) | 2021-05-06 | 2024-05-01 | アムジェン リサーチ （ミュニック） ゲゼルシャフト ミット ベシュレンクテル ハフツング | 増殖性疾患で使用されるｃｄ２０及びｃｄ２２標的化抗原結合分子 |
| US20240317856A1 (en) * | 2021-05-10 | 2024-09-26 | Amgen Inc. | Dosing regimen for combination therapy targeting dll3 and pd-1 |
| IL308154A (en) | 2021-07-30 | 2023-12-01 | Affimed Gmbh | Double structure antibodies |
| CA3231172A1 (en) * | 2021-09-16 | 2023-03-23 | Martin Schroeder | Pd-l1 targeting fusion proteins and methods of use thereof |
| TW202332695A (zh) | 2021-10-15 | 2023-08-16 | 德商安美基研究（慕尼黑）公司 | 結合ｃｄ１９的ｔ細胞接合劑之皮下投與 |
| AR127458A1 (es) | 2021-10-27 | 2024-01-24 | Amgen Inc | Predicción basada en aprendizaje profundo usando espectroscopia |
| AU2022381918A1 (en) | 2021-11-03 | 2024-06-13 | Affimed Gmbh | Bispecific cd16a binders |
| JP2024543822A (ja) | 2021-11-03 | 2024-11-26 | アフィメド ゲーエムベーハー | 二重特異性ｃｄ１６ａバインダー |
| CN116554340A (zh) * | 2022-01-28 | 2023-08-08 | 江苏众红生物工程创药研究院有限公司 | 新型长效化和高活性且更安全的抗体构建体 |
| TW202346368A (zh) | 2022-05-12 | 2023-12-01 | 德商安美基研究（慕尼黑）公司 | 具有增加的選擇性的多鏈多靶向性雙特異性抗原結合分子 |
| EP4587474A2 (en) | 2022-09-14 | 2025-07-23 | Amgen Inc. | Bispecific molecule stabilizing composition |
| EP4598958A1 (en) | 2022-10-05 | 2025-08-13 | Amgen Inc. | Combination therapies comprising t-cell redirecting therapies and agonistic anti-il-2r antibodies or fragments thereof |
| WO2024173607A2 (en) * | 2023-02-14 | 2024-08-22 | Evolveimmune Therapeutics, Inc. | Combination of bispecific antibodies and chimeric antigen receptor t cells for treatment |
| CN121335928A (zh) | 2023-04-28 | 2026-01-13 | Xencor股份有限公司 | 正交多聚体蛋白 |
| TW202521428A (zh) | 2023-08-22 | 2025-06-01 | 美商安進公司 | 用於高效包裝藥物產品之方法及組件 |
| WO2025101672A1 (en) | 2023-11-06 | 2025-05-15 | City Of Hope | Methods comprising oncolytic viruses expressing cd19t and bispecific t cell engagers |
| TW202540166A (zh) | 2024-03-01 | 2025-10-16 | 德商安美基研究（慕尼黑）公司 | 用於治療自體免疫性疾病／自體免疫性病症的ｃｄ１９選擇性ｔ細胞接合分子 |
| WO2025226754A1 (en) | 2024-04-23 | 2025-10-30 | Amgen Inc. | Method for predicting osmolality of protein solutions |
Family Cites Families (228)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US3691016A (en) | 1970-04-17 | 1972-09-12 | Monsanto Co | Process for the preparation of insoluble enzymes |
| CA1023287A (en) | 1972-12-08 | 1977-12-27 | Boehringer Mannheim G.M.B.H. | Process for the preparation of carrier-bound proteins |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4195128A (en) | 1976-05-03 | 1980-03-25 | Bayer Aktiengesellschaft | Polymeric carrier bound ligands |
| US4330440A (en) | 1977-02-08 | 1982-05-18 | Development Finance Corporation Of New Zealand | Activated matrix and method of activation |
| CA1093991A (en) | 1977-02-17 | 1981-01-20 | Hideo Hirohara | Enzyme immobilization with pullulan gel |
| US4229537A (en) | 1978-02-09 | 1980-10-21 | New York University | Preparation of trichloro-s-triazine activated supports for coupling ligands |
| US4263428A (en) | 1978-03-24 | 1981-04-21 | The Regents Of The University Of California | Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
| US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
| 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 |
| EP0088046B1 (de) | 1982-02-17 | 1987-12-09 | Ciba-Geigy Ag | Lipide in wässriger Phase |
| US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
| US4447224A (en) | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
| US4487603A (en) | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
| US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
| HUT35524A (en) | 1983-08-02 | 1985-07-29 | Hoechst Ag | Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance |
| DE3474511D1 (en) | 1983-11-01 | 1988-11-17 | Terumo Corp | Pharmaceutical composition containing urokinase |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| US4694778A (en) | 1984-05-04 | 1987-09-22 | Anicon, Inc. | Chemical vapor deposition wafer boat |
| JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
| EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| US4879231A (en) | 1984-10-30 | 1989-11-07 | Phillips Petroleum Company | Transformation of yeasts of the genus pichia |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US4751180A (en) | 1985-03-28 | 1988-06-14 | Chiron Corporation | Expression using fused genes providing for protein product |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
| JPS63502716A (ja) | 1986-03-07 | 1988-10-13 | マサチューセッツ・インステチュート・オブ・テクノロジー | 糖タンパク安定性の強化方法 |
| 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 |
| GB8610600D0 (en) | 1986-04-30 | 1986-06-04 | Novo Industri As | Transformation of trichoderma |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| WO1988001649A1 (en) | 1986-09-02 | 1988-03-10 | Genex Corporation | Single polypeptide chain binding molecules |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2, Inc., Danville, Calif. | Geänderte antikörper. |
| AU612370B2 (en) | 1987-05-21 | 1991-07-11 | Micromet Ag | Targeted multifunctional proteins |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US5476996A (en) | 1988-06-14 | 1995-12-19 | Lidak Pharmaceuticals | Human immune system in non-human animal |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| EP0402226A1 (en) | 1989-06-06 | 1990-12-12 | Institut National De La Recherche Agronomique | Transformation vectors for yeast yarrowia |
| US5683888A (en) | 1989-07-22 | 1997-11-04 | University Of Wales College Of Medicine | Modified bioluminescent proteins and their use |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US5292658A (en) | 1989-12-29 | 1994-03-08 | University Of Georgia Research Foundation, Inc. Boyd Graduate Studies Research Center | Cloning and expressions of Renilla luciferase |
| CA2050918A1 (en) | 1990-01-12 | 1991-07-13 | Raju Kucherlapati | Generation of xenogeneic antibodies |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| WO1996033735A1 (en) | 1995-04-27 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| DE69133476T2 (de) | 1990-08-29 | 2006-01-05 | GenPharm International, Inc., Palo Alto | Transgene Mäuse fähig zur Produktion heterologer Antikörper |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| CA2090473A1 (en) | 1990-08-29 | 1992-03-01 | Robert M. Kay | Homologous recombinatin in mammalian cells |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| WO1994025585A1 (en) | 1993-04-26 | 1994-11-10 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| DK0575319T3 (da) | 1991-03-11 | 2000-07-10 | Univ Georgia Res Found | Kloning og ekspression af Renilla-luciferase |
| WO1992022670A1 (en) | 1991-06-12 | 1992-12-23 | Genpharm International, Inc. | Early detection of transgenic embryos |
| AU675916B2 (en) | 1991-06-14 | 1997-02-27 | Genentech Inc. | Method for making humanized antibodies |
| WO1992022645A1 (en) | 1991-06-14 | 1992-12-23 | Genpharm International, Inc. | Transgenic immunodeficient non-human animals |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| JPH07503132A (ja) | 1991-12-17 | 1995-04-06 | ジェンファーム インターナショナル，インコーポレイティド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
| WO1993015722A1 (en) | 1992-02-07 | 1993-08-19 | Syntex (Usa) Inc. | Controlled delivery of pharmaceuticals from preformed porous microparticles |
| EP0648265A4 (en) | 1992-06-18 | 1996-12-04 | Genpharm Int | PROCESS FOR THE PRODUCTION OF NON-HUMAN TRANSGENIC ANIMALS HAVING AN ARTIFICIAL YEAST CHROMOSOME. |
| SG48760A1 (en) | 1992-07-24 | 2003-03-18 | Abgenix Inc | Generation of xenogenetic antibodies |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| WO1994010308A1 (en) | 1992-10-23 | 1994-05-11 | Immunex Corporation | Methods of preparing soluble, oligomeric proteins |
| US5981175A (en) | 1993-01-07 | 1999-11-09 | Genpharm Internation, Inc. | Methods for producing recombinant mammalian cells harboring a yeast artificial chromosome |
| CZ307995A3 (en) | 1993-05-24 | 1996-10-16 | Immunex Corp | Ligands for flt3 receptors |
| US7045128B2 (en) | 1993-05-24 | 2006-05-16 | Immunex Corporation | Antibodies against flt3-ligand |
| JP3810791B2 (ja) | 1993-09-10 | 2006-08-16 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | 緑色蛍光タンパク質の使用 |
| US5625825A (en) | 1993-10-21 | 1997-04-29 | Lsi Logic Corporation | Random number generating apparatus for an interface unit of a carrier sense with multiple access and collision detect (CSMA/CD) ethernet data network |
| WO1995021191A1 (en) | 1994-02-04 | 1995-08-10 | William Ward | Bioluminescent indicator based upon the expression of a gene for a modified green-fluorescent protein |
| US5643763A (en) | 1994-11-04 | 1997-07-01 | Genpharm International, Inc. | Method for making recombinant yeast artificial chromosomes by minimizing diploid doubling during mating |
| US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
| US5777079A (en) | 1994-11-10 | 1998-07-07 | The Regents Of The University Of California | Modified green fluorescent proteins |
| CA2219486A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5811524A (en) | 1995-06-07 | 1998-09-22 | Idec Pharmaceuticals Corporation | Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof |
| DE69621940T2 (de) | 1995-08-18 | 2003-01-16 | Morphosys Ag | Protein-/(poly)peptidbibliotheken |
| ATE352613T1 (de) | 1995-08-29 | 2007-02-15 | Kirin Brewery | Chimäres tier und methode zu dessen herstellung |
| US5874304A (en) | 1996-01-18 | 1999-02-23 | University Of Florida Research Foundation, Inc. | Humanized green fluorescent protein genes and methods |
| US5804387A (en) | 1996-02-01 | 1998-09-08 | The Board Of Trustees Of The Leland Stanford Junior University | FACS-optimized mutants of the green fluorescent protein (GFP) |
| US5876995A (en) | 1996-02-06 | 1999-03-02 | Bryan; Bruce | Bioluminescent novelty items |
| US5925558A (en) | 1996-07-16 | 1999-07-20 | The Regents Of The University Of California | Assays for protein kinases using fluorescent protein substrates |
| US5976796A (en) | 1996-10-04 | 1999-11-02 | Loma Linda University | Construction and expression of renilla luciferase and green fluorescent protein fusion genes |
| DK1500329T3 (da) | 1996-12-03 | 2012-07-09 | Amgen Fremont Inc | Humane antistoffer, der specifikt binder TNF-alfa |
| JP3795533B2 (ja) | 1996-12-12 | 2006-07-12 | プロルーム・リミテツド | 感染性物質を検出及び同定するための方法及び装置 |
| DE69833755T2 (de) | 1997-05-21 | 2006-12-28 | Biovation Ltd. | Verfahren zur herstellung von nicht-immunogenen proteinen |
| JP2002507410A (ja) | 1998-03-27 | 2002-03-12 | プロルーム・リミテッド | ルシフェラーゼ、蛍光タンパク質、ルシフェラーゼおよび蛍光タンパク質をコードする核酸および、診断、高処理スクリーニングおよび新規アイテムにおけるその使用 |
| NZ507381A (en) | 1998-04-21 | 2003-12-19 | Micromet Ag | CD19xCD3 specific polypeptides and uses thereof |
| EP1100830B1 (en) | 1998-07-28 | 2003-10-01 | Micromet AG | Heterominibodies |
| EP1051432B1 (en) | 1998-12-08 | 2007-01-24 | Biovation Limited | Method for reducing immunogenicity of proteins |
| US6833268B1 (en) | 1999-06-10 | 2004-12-21 | Abgenix, Inc. | Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions |
| EP1461442B1 (en) | 2001-11-30 | 2017-09-06 | Amgen Fremont Inc. | Transgenic animals bearing human ig lambda light chain genes |
| WO2005010151A2 (en) | 2003-06-27 | 2005-02-03 | Abgenix, Inc | Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof |
| WO2005032491A2 (en) | 2003-10-03 | 2005-04-14 | Board Of Regents, University Of Texas System | Methods and compositions for mycoplasma pneumoniae exotoxins |
| HRP20110187T1 (hr) | 2003-10-16 | 2011-04-30 | Micromet Ag | Multispecifične deimunizirane tvari koje vežu cd3 |
| EP1697520A2 (en) | 2003-12-22 | 2006-09-06 | Xencor, Inc. | Fc polypeptides with novel fc ligand binding sites |
| EP3673919A1 (en) | 2005-06-14 | 2020-07-01 | Amgen Inc. | Self-buffering protein formulations |
| EP1940881B1 (en) | 2005-10-11 | 2016-11-30 | Amgen Research (Munich) GmbH | Compositions comprising cross-species-specific antibodies and uses thereof |
| AU2007212147A1 (en) * | 2006-02-03 | 2007-08-16 | Medimmune, Llc | Protein formulations |
| TW200745163A (en) | 2006-02-17 | 2007-12-16 | Syntonix Pharmaceuticals Inc | Peptides that block the binding of IgG to FcRn |
| GB0614780D0 (en) | 2006-07-25 | 2006-09-06 | Ucb Sa | Biological products |
| PL2142533T3 (pl) | 2007-03-30 | 2012-04-30 | Hoffmann La Roche | Pochodne imidazolidynonu |
| EP2155783B2 (en) * | 2007-04-03 | 2022-10-19 | Amgen Research (Munich) GmbH | Cross-species-specific cd3-epsilon binding domain |
| AU2008234020B2 (en) | 2007-04-03 | 2013-02-07 | Amgen Research (Munich) Gmbh | Cross-species-specific CD3-epsilon binding domain |
| CA2682605A1 (en) * | 2007-04-18 | 2008-10-30 | Zymogenetics, Inc. | Single chain fc, methods of making and methods of treatment |
| KR20100021601A (ko) * | 2007-05-14 | 2010-02-25 | 바이오겐 아이덱 엠에이 인코포레이티드 | 단일-쇄 Ｆｃ(ＳｃＦｃ) 부분, 이를 포함하는 결합 폴리펩타이드, 및 이에 관련된 방법 |
| WO2009127691A1 (en) | 2008-04-17 | 2009-10-22 | Ablynx N.V. | Peptides capable of binding to serum proteins and compounds, constructs and polypeptides comprising the same |
| JP5739326B2 (ja) | 2008-04-25 | 2015-06-24 | ザイモジェネティクス， インコーポレイテッド | Ｂ細胞上でのｂｃｍａタンパク発現レベル及び診断法における使用 |
| CA2738568C (en) * | 2008-10-01 | 2024-02-20 | Micromet Ag | Cross-species-specific single domain bispecific single chain antibody |
| HRP20160684T1 (hr) | 2008-10-01 | 2016-07-15 | Amgen Research (Munich) Gmbh | Bispecifično jednolančano protutijelo psmaxcd3 s međuvrsnom specifičnošću |
| WO2010045261A1 (en) * | 2008-10-13 | 2010-04-22 | Zymogenetics, Llc | Single chain fc type iii interferons and methods of using same |
| US8311684B2 (en) * | 2008-12-17 | 2012-11-13 | Pratt & Whitney Canada Corp. | Output flow control in load compressor |
| DK2406284T5 (en) | 2009-03-10 | 2017-06-12 | Biogen Ma Inc | ANTI-BCMA ANTIBODIES |
| AR076284A1 (es) | 2009-04-29 | 2011-06-01 | Bayer Schering Pharma Ag | Inmunoconjugados de antimesotelina y usos de los mismos |
| RU2607374C2 (ru) | 2009-10-30 | 2017-01-10 | Новозаймс Байофарма Дк А/С | Варианты альбумина |
| EP2516468B1 (en) | 2009-12-23 | 2016-03-02 | Synimmune GmbH | Anti-flt3 antibodies and methods of using the same |
| US20130129723A1 (en) | 2009-12-29 | 2013-05-23 | Emergent Product Development Seattle, Llc | Heterodimer Binding Proteins and Uses Thereof |
| TWI653333B (zh) | 2010-04-01 | 2019-03-11 | 安進研究（慕尼黑）有限責任公司 | 跨物種專一性之ＰＳＭＡｘＣＤ３雙專一性單鏈抗體 |
| CA2800173C (en) | 2010-05-21 | 2019-05-14 | Ulrik Nielsen | Bi-specific fusion proteins |
| EP2635598A1 (en) | 2010-11-01 | 2013-09-11 | Novozymes Biopharma DK A/S | Albumin variants |
| SG10201508789TA (en) * | 2010-11-10 | 2015-11-27 | Amgen Res Munich Gmbh | Prevention of adverse effects caused by cd3 specific binding domains |
| JP2014500879A (ja) | 2010-11-16 | 2014-01-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｂｃｍａ発現に相関性を有する疾患を治療する因子及び方法 |
| EP2647707B1 (en) * | 2010-11-30 | 2018-09-12 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
| PH12013501323A1 (en) | 2010-12-20 | 2013-08-28 | Genentech Inc | Anti-mesothelin antibodies and immunoconjugates |
| US9409950B2 (en) * | 2010-12-23 | 2016-08-09 | Biogen Ma Inc. | Linker peptides and polypeptides comprising same |
| MX353816B (es) | 2011-05-05 | 2018-01-30 | Albumedix As | Variantes de albumina. |
| WO2013026837A1 (en) * | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
| WO2013026833A1 (en) | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對ｂｃｍａ之e3以及ｃｄ３的結合分子 |
| CL2014001263A1 (es) | 2011-11-15 | 2014-10-10 | Boehringer Ingelheim Int | Molécula de unión biespecífica para bcma y cd3; secuencia de ácido nucleico que la codifica; vector ; célula; composición farmacéutica que comprende a la molécula de unión; uso para tratar enfermedades relacionadas a transtornos de células plasmáticas, trastornos de células b correlacionados con la expresión de bcma y enfermedades autoinmunes. |
| CN104168922A (zh) | 2011-11-16 | 2014-11-26 | 安姆根有限公司 | 治疗表皮生长因子缺失突变体viii相关疾病的方法 |
| EP2780364A2 (en) | 2011-11-18 | 2014-09-24 | Eleven Biotherapeutics, Inc. | Proteins with improved half-life and other properties |
| DK2794658T3 (en) * | 2011-12-19 | 2017-06-19 | Synimmune Gmbh | BISPECIFIC ANTIBODY MOLECULE |
| HUE037021T2 (hu) | 2012-02-24 | 2018-08-28 | Abbvie Stemcentrx Llc | DLL3- modulátorok és eljárások alkalmazásukra |
| MX353382B (es) | 2012-03-01 | 2018-01-10 | Amgen Res Munich Gmbh | Moleculas de union polipeptido de larga duracion. |
| PL2825556T3 (pl) | 2012-03-16 | 2018-10-31 | Albumedix A/S | Warianty albuminy |
| JP6154895B2 (ja) * | 2012-06-07 | 2017-06-28 | デューク ユニバーシティー | ヒト二重特異性ＥＧＦＲｖＩＩＩ抗体結合分子 |
| US20140004121A1 (en) | 2012-06-27 | 2014-01-02 | Amgen Inc. | Anti-mesothelin binding proteins |
| HK1207575A1 (en) | 2012-07-13 | 2016-02-05 | Zymeworks, Inc. | Bispecific asymmetric heterodimers comprising anti-cd3 constructs |
| AU2013306076B2 (en) * | 2012-08-21 | 2018-01-25 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Mesothelin domain-specific monoclonal antibodies and use thereof |
| JOP20200236A1 (ar) | 2012-09-21 | 2017-06-16 | Regeneron Pharma | الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها |
| AU2013343503B2 (en) | 2012-11-08 | 2017-12-14 | Albumedix Ltd. | Albumin variants |
| US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
| US9243058B2 (en) | 2012-12-07 | 2016-01-26 | Amgen, Inc. | BCMA antigen binding proteins |
| US20140377269A1 (en) | 2012-12-19 | 2014-12-25 | Adimab, Llc | Multivalent antibody analogs, and methods of their preparation and use |
| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| JO3519B1 (ar) | 2013-01-25 | 2020-07-05 | Amgen Inc | تركيبات أجسام مضادة لأجل cdh19 و cd3 |
| JP2016507523A (ja) | 2013-02-05 | 2016-03-10 | エンクマフ アーゲー | ＣＤ３εおよびＢＣＭＡに対する二重特異的抗体 |
| GB201302447D0 (en) * | 2013-02-12 | 2013-03-27 | Oxford Biotherapeutics Ltd | Therapeutic and diagnostic target |
| EA031214B1 (ru) | 2013-02-26 | 2018-12-28 | Роше Гликарт Аг | Биспецифические антигенсвязывающие молекулы, активирующие т-клетки |
| TW201444872A (zh) * | 2013-03-06 | 2014-12-01 | Merrimack Pharmaceuticals Inc | 抗Ｃ－ＭＥＴ串聯Ｆｃ雙特異性抗體 |
| US20140251168A1 (en) * | 2013-03-06 | 2014-09-11 | E I Du Pont De Nemours And Company | Printing form and a process for preparing a printing form using two-step cure |
| US9546203B2 (en) * | 2013-03-14 | 2017-01-17 | Amgen Inc. | Aglycosylated Fc-containing polypeptides with cysteine substitutions |
| AR095374A1 (es) | 2013-03-15 | 2015-10-14 | Amgen Res Munich Gmbh | Moléculas de unión para bcma y cd3 |
| US11634502B2 (en) | 2013-03-15 | 2023-04-25 | Amgen Inc. | Heterodimeric bispecific antibodies |
| US20140302037A1 (en) | 2013-03-15 | 2014-10-09 | Amgen Inc. | BISPECIFIC-Fc MOLECULES |
| US20140308285A1 (en) | 2013-03-15 | 2014-10-16 | Amgen Inc. | Heterodimeric bispecific antibodies |
| US9587235B2 (en) * | 2013-03-15 | 2017-03-07 | Atyr Pharma, Inc. | Histidyl-tRNA synthetase-Fc conjugates |
| AU2014228924B2 (en) * | 2013-03-15 | 2019-04-18 | Amgen Inc. | Human PAC1 antibodies |
| DK2970449T3 (da) | 2013-03-15 | 2019-11-25 | Amgen Res Munich Gmbh | Enkeltkædede bindingsmolekyler, der omfatter n-terminal abp |
| EP3019532B1 (en) * | 2013-07-09 | 2019-01-02 | Duke University | Human bispecific egfrviii antibody engaging molecules |
| DK3030581T3 (da) * | 2013-08-07 | 2021-04-12 | Affimed Gmbh | Antistofbindingssteder, der er specifikke for egfrviii |
| EP2840091A1 (en) | 2013-08-23 | 2015-02-25 | MacroGenics, Inc. | Bi-specific diabodies that are capable of binding gpA33 and CD3 and uses thereof |
| AR097648A1 (es) * | 2013-09-13 | 2016-04-06 | Amgen Inc | Combinación de factores epigenéticos y compuestos biespecíficos que tienen como diana cd33 y cd3 en el tratamiento de leucemia mieloide |
| US20160257748A1 (en) | 2013-09-25 | 2016-09-08 | Amgen Inc. | V-c-fc-v-c antibody |
| GB2519786A (en) | 2013-10-30 | 2015-05-06 | Sergej Michailovic Kiprijanov | Multivalent antigen-binding protein molecules |
| SG10201809385RA (en) | 2013-12-17 | 2018-11-29 | Genentech Inc | Anti-cd3 antibodies and methods of use |
| CN105916880B (zh) | 2014-01-15 | 2020-01-17 | 豪夫迈·罗氏有限公司 | 具有改善的蛋白A结合作用的Fc区变体 |
| JP6775422B2 (ja) | 2014-03-28 | 2020-10-28 | ゼンコー・インコーポレイテッドＸｅｎｃｏｒ、 Ｉｎｃ． | Ｃｄ３８及びｃｄ３に結合する二重特異性抗体 |
| AU2015265457B2 (en) | 2014-05-28 | 2021-02-18 | Zymeworks Bc Inc. | Modified antigen binding polypeptide constructs and uses thereof |
| EP3174903B1 (en) | 2014-07-31 | 2024-04-10 | Amgen Research (Munich) GmbH | Bispecific single chain antibody construct with enhanced tissue distribution |
| MX377344B (es) | 2014-07-31 | 2025-03-07 | Amgen Res Munich Gmbh | Constructos de anticuerpos de cadena sencilla biespecífica específicos para especies cruzadas optimizadas. |
| CN106661120B (zh) | 2014-08-04 | 2021-10-01 | 豪夫迈·罗氏有限公司 | 双特异性t细胞活化性抗原结合分子 |
| US20170247476A1 (en) | 2014-09-25 | 2017-08-31 | Amgen Inc. | Protease-activatable bispecific proteins |
| MA40894A (fr) | 2014-11-04 | 2017-09-12 | Glenmark Pharmaceuticals Sa | Immunoglobulines hétéro-dimères reciblant des lymphocytes t cd3/cd38 et leurs procédés de production |
| CN110894240B (zh) | 2014-11-26 | 2022-04-15 | 森科股份有限公司 | 结合cd3和肿瘤抗原的异二聚体抗体 |
| MX2017006918A (es) | 2014-11-26 | 2018-01-25 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38. |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| CN104829728B (zh) | 2015-01-21 | 2019-03-12 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体her2xcd3的构建及应用 |
| CN104829726B (zh) | 2015-01-21 | 2019-03-05 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体cd19xcd3的构建及应用 |
| CN104829727B (zh) * | 2015-01-21 | 2019-03-12 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体cd19×cd3的构建及应用 |
| EP4039710A3 (en) | 2015-01-23 | 2022-10-19 | Sanofi | Anti-cd3 antibodies, anti-cd123 antibodies and bispecific antibodies specifically binding to cd3 and/or cd123 |
| EP3253414A4 (en) | 2015-02-05 | 2018-07-11 | The University Of Queensland | Targeting constructs for delivery of payloads |
| DK3283524T3 (da) | 2015-04-17 | 2023-05-30 | Amgen Res Munich Gmbh | BISPECIFIKKE ANTISTOFKONSTRUKTIONER MOD CDH3 og CD3 |
| TWI796283B (zh) | 2015-07-31 | 2023-03-21 | 德商安美基研究（慕尼黑）公司 | Ｍｓｌｎ及ｃｄ３抗體構築體 |
| EA039859B1 (ru) * | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TW202346349A (zh) * | 2015-07-31 | 2023-12-01 | 德商安美基研究（慕尼黑）公司 | Dll3及cd3抗體構築體 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究（慕尼黑）公司 | Egfrviii及cd3抗體構築體 |
| TWI717375B (zh) | 2015-07-31 | 2021-02-01 | 德商安美基研究（慕尼黑）公司 | Ｃｄ７０及ｃｄ３抗體構築體 |
| TWI829617B (zh) * | 2015-07-31 | 2024-01-21 | 德商安美基研究（慕尼黑）公司 | Ｆｌｔ３及ｃｄ３抗體構築體 |
| JO3799B1 (ar) | 2015-08-17 | 2021-01-31 | Janssen Pharmaceutica Nv | الأجسام المضادة ل bcma، جزيئات ربط الانتيجين ثنائية التحديد التي تربط bcma و cd3، و استخداماتها |
| CN108431042A (zh) | 2015-11-02 | 2018-08-21 | 詹森药业有限公司 | 抗-il1rap抗体，结合il1rap和cd3的双特异性抗原结合分子及其用途 |
| US9552854B1 (en) | 2015-11-10 | 2017-01-24 | Intel Corporation | Register files including distributed capacitor circuit blocks |
| CN116063544A (zh) | 2016-02-03 | 2023-05-05 | 安进研发（慕尼黑）股份有限公司 | Bcma和cd3双特异性t细胞接合抗体构建体 |
| CN114716557A (zh) | 2016-02-03 | 2022-07-08 | 安进研发（慕尼黑）股份有限公司 | Psma和cd3双特异性t细胞接合抗体构建体 |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| TWI790206B (zh) | 2016-07-18 | 2023-01-21 | 法商賽諾菲公司 | 特異性結合至ｃｄ３和ｃｄ１２３的雙特異性抗體樣結合蛋白 |
| TWI781108B (zh) | 2016-07-20 | 2022-10-21 | 比利時商健生藥品公司 | 抗ｇｐｒｃ５ｄ抗體、結合ｇｐｒｃ５ｄ與ｃｄ３之雙特異性抗原結合分子及其用途 |
| CA3037732A1 (en) | 2016-09-23 | 2018-03-29 | Regeneron Pharmaceuticals, Inc. | Anti-steap2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind steap2 and cd3, and uses thereof |
| US10941208B2 (en) | 2016-09-23 | 2021-03-09 | Regeneron Pharmaceuticals, Inc. | Anti-MUC16 antibodies |
| EP4295918A3 (en) | 2016-11-02 | 2024-03-20 | Bristol-Myers Squibb Company | Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma |
| JOP20190189A1 (ar) * | 2017-02-02 | 2019-08-01 | Amgen Res Munich Gmbh | تركيبة صيدلانية ذات درجة حموضة منخفضة تتضمن بنيات جسم مضاد يستهدف الخلية t |
| TWI868050B (zh) | 2017-05-05 | 2025-01-01 | 美商安進公司 | 用於改良儲存及投與之包含雙特異性抗體構築體之醫藥組成物 |
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