JP6636925B2 - 細胞障害性ペプチドおよびその抱合体 - Google Patents
細胞障害性ペプチドおよびその抱合体 Download PDFInfo
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- JP6636925B2 JP6636925B2 JP2016540522A JP2016540522A JP6636925B2 JP 6636925 B2 JP6636925 B2 JP 6636925B2 JP 2016540522 A JP2016540522 A JP 2016540522A JP 2016540522 A JP2016540522 A JP 2016540522A JP 6636925 B2 JP6636925 B2 JP 6636925B2
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Classifications
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- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361917293P | 2013-12-17 | 2013-12-17 | |
| US61/917,293 | 2013-12-17 | ||
| PCT/US2014/070800 WO2015095301A2 (en) | 2013-12-17 | 2014-12-17 | Cytotoxic peptides and conjugates thereof |
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| JP2019176561A Division JP2020023514A (ja) | 2013-12-17 | 2019-09-27 | 細胞障害性ペプチドおよびその抱合体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2014214751B2 (en) * | 2013-02-08 | 2017-06-01 | Novartis Ag | Specific sites for modifying antibodies to make immunoconjugates |
| CN110143999B (zh) | 2013-03-15 | 2023-12-05 | 酵活英属哥伦比亚省公司 | 具细胞毒性和抗有丝分裂的化合物以及其使用方法 |
| WO2015095952A1 (en) | 2013-12-27 | 2015-07-02 | The Centre For Drug Research And Development | Var2csa-drug conjugates |
| EP3086815B1 (en) | 2013-12-27 | 2022-02-09 | Zymeworks Inc. | Sulfonamide-containing linkage systems for drug conjugates |
| WO2015138615A2 (en) * | 2014-03-12 | 2015-09-17 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
| EA201692530A1 (ru) | 2014-06-13 | 2017-07-31 | Новартис Аг | Цитотоксические пептиды и их конъюгаты |
| DK3194421T3 (da) | 2014-09-17 | 2022-02-14 | Zymeworks Inc | Cytotoksiske og antimitotiske forbindelser samt fremgangsmåder til anvendelse heraf |
| US11566082B2 (en) | 2014-11-17 | 2023-01-31 | Cytiva Bioprocess R&D Ab | Mutated immunoglobulin-binding polypeptides |
| WO2017194593A1 (en) | 2016-05-11 | 2017-11-16 | Ge Healthcare Bioprocess R&D Ab | Method of cleaning and/or sanitizing a separation matrix |
| US10703774B2 (en) | 2016-09-30 | 2020-07-07 | Ge Healthcare Bioprocess R&D Ab | Separation method |
| US10654887B2 (en) | 2016-05-11 | 2020-05-19 | Ge Healthcare Bio-Process R&D Ab | Separation matrix |
| US10889615B2 (en) | 2016-05-11 | 2021-01-12 | Cytiva Bioprocess R&D Ab | Mutated immunoglobulin-binding polypeptides |
| CN109071613A (zh) | 2016-05-11 | 2018-12-21 | 通用电气医疗集团生物工艺研发股份公司 | 分离基质 |
| JP7106187B2 (ja) | 2016-05-11 | 2022-07-26 | サイティバ・バイオプロセス・アールアンドディ・アクチボラグ | 分離マトリックスを保存する方法 |
| US10730908B2 (en) | 2016-05-11 | 2020-08-04 | Ge Healthcare Bioprocess R&D Ab | Separation method |
| JP7031934B2 (ja) | 2016-05-11 | 2022-03-08 | サイティバ・バイオプロセス・アールアンドディ・アクチボラグ | 分離マトリックス |
| US12448411B2 (en) | 2016-09-30 | 2025-10-21 | Cytiva Bioprocess R&D Ab | Separation method |
| US10517958B2 (en) | 2016-10-04 | 2019-12-31 | Zymeworks Inc. | Compositions and methods for the treatment of platinum-drug resistant cancer |
| JOP20190187A1 (ar) | 2017-02-03 | 2019-08-01 | Novartis Ag | مترافقات عقار جسم مضاد لـ ccr7 |
| TW202014209A (zh) * | 2018-06-20 | 2020-04-16 | 瑞士商諾華公司 | 用於消融造血幹細胞之抗體藥物軛合物 |
| CN113365969B (zh) * | 2018-11-23 | 2023-09-15 | 上海药明合联生物技术有限公司 | 含有邻苯二甲醛的连接体及其用于制备抗体-药物缀合物的用途 |
| US20230129674A1 (en) * | 2020-03-09 | 2023-04-27 | Sigma-Aldrich Co. Llc | Efficient preparation of dolastatin and auristatin analogs through a common intermediate |
| US20230181756A1 (en) | 2020-04-30 | 2023-06-15 | Novartis Ag | Ccr7 antibody drug conjugates for treating cancer |
| JP7670072B2 (ja) * | 2021-01-18 | 2025-04-30 | 味の素株式会社 | 化合物またはその塩、およびそれらにより得られる抗体 |
| WO2023061405A1 (zh) * | 2021-10-12 | 2023-04-20 | 成都科岭源医药技术有限公司 | 一种高稳定性的靶向接头-药物偶联物 |
| CN119894535A (zh) * | 2022-07-27 | 2025-04-25 | 祐方有限公司 | 奥瑞他汀衍生物及其偶联物 |
| WO2024152000A1 (en) * | 2023-01-13 | 2024-07-18 | The Trustees Of The University Of Pennsylvania | Disruptable linker compositions, switchable bispecific t cell nanoengager (switch-bite) compositions comprising the same, and methods of use thereof |
| AU2024256916A1 (en) | 2023-04-18 | 2025-12-04 | Astrazeneca Ab | Conjugates comprising cleavable linkers |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| ES2144421T3 (es) | 1991-08-09 | 2000-06-16 | Teikoku Hormone Mfg Co Ltd | Nuevo derivado tetrapeptidico. |
| WO1995009864A1 (en) | 1993-10-01 | 1995-04-13 | Teikoku Hormone Mfg. Co., Ltd. | Novel peptide derivative |
| US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| EP0831100B1 (en) | 1995-04-21 | 2000-10-11 | Teikoku Hormone Mfg. Co., Ltd. | Novel peptide derivatives |
| ATE386802T1 (de) | 1997-06-12 | 2008-03-15 | Novartis Int Pharm Ltd | Künstliche antikörperpolypeptide |
| US6153655A (en) | 1998-04-17 | 2000-11-28 | Enzon, Inc. | Terminally-branched polymeric linkers and polymeric conjugates containing the same |
| US7803915B2 (en) | 2001-06-20 | 2010-09-28 | Genentech, Inc. | Antibody compositions for the diagnosis and treatment of tumor |
| US20090068178A1 (en) | 2002-05-08 | 2009-03-12 | Genentech, Inc. | Compositions and Methods for the Treatment of Tumor of Hematopoietic Origin |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| KR101520209B1 (ko) | 2003-11-06 | 2015-05-13 | 시애틀 지네틱스, 인크. | 리간드에 접합될 수 있는 모노메틸발린 화합물 |
| EP1817336B1 (en) | 2004-11-12 | 2019-01-09 | Seattle Genetics, Inc. | Auristatins having an aminobenzoic acid unit at the n terminus |
| EP1817341A2 (en) | 2004-11-29 | 2007-08-15 | Seattle Genetics, Inc. | Engineered antibodies and immunoconjugates |
| CN101287498B (zh) | 2005-06-20 | 2013-03-27 | Psma开发有限公司 | Psma抗体-药物缀合物 |
| US7750116B1 (en) | 2006-02-18 | 2010-07-06 | Seattle Genetics, Inc. | Antibody drug conjugate metabolites |
| WO2007103288A2 (en) | 2006-03-02 | 2007-09-13 | Seattle Genetics, Inc. | Engineered antibody drug conjugates |
| AR059900A1 (es) | 2006-03-17 | 2008-05-07 | Genentech Inc | Anticuerpos anti-tat226 e inmunoconjugados |
| DK2211904T3 (en) | 2007-10-19 | 2016-10-24 | Seattle Genetics Inc | Cd19-binding agents and uses thereof |
| ES2523033T3 (es) | 2008-03-18 | 2014-11-20 | Seattle Genetics, Inc. | Conjugados enlazadores del fármaco auriestatina |
| EP2621508B1 (de) | 2010-09-29 | 2015-08-26 | Seattle Genetics, Inc. | N-carboxyalkyl-auristatine und ihre verwendung |
| TWI545134B (zh) | 2010-10-22 | 2016-08-11 | 西雅圖遺傳學公司 | 以奧裡斯他汀（ＡＵＲＩＳＴＡＴＩＮ）為主之抗體藥物結合物及ＰＩ３Ｋ－ＡＫＴ ｍＴＯＲ路徑抑制劑間的協同功效 |
| WO2012113847A1 (en) | 2011-02-25 | 2012-08-30 | Lonza Ltd | Branched linker for protein drug conjugates |
| CN103764667B (zh) | 2011-03-16 | 2017-06-20 | 西雅图基因公司 | N‑羧烷基耳他汀类及其应用 |
| CN103826661B (zh) | 2011-04-21 | 2019-03-05 | 西雅图基因公司 | 新的结合剂-药物缀合物(adc)及其用途 |
| DK2714684T3 (en) | 2011-05-27 | 2018-11-26 | Ambrx Inc | COMPOSITIONS CONTAINING, PROCEDURE INVOLVING, AND APPLICATIONS OF NON-NATURAL AMINO ACID-BONDED DOLASTATIN DERIVATIVES |
| EP2780039B9 (en) | 2011-11-17 | 2018-04-18 | Pfizer Inc | Cytotoxic peptides and antibody drug conjugates thereof |
| CA3111357A1 (en) * | 2011-12-23 | 2013-06-27 | Pfizer Inc. | Engineered antibody constant regions for site-specific conjugation and methods and uses therefor |
| BR112014030098A2 (pt) | 2012-06-04 | 2017-07-25 | Irm Llc | métodos de rotulagem específica de sítio e moléculas produzidas pelos mesmos |
| AU2014214751B2 (en) * | 2013-02-08 | 2017-06-01 | Novartis Ag | Specific sites for modifying antibodies to make immunoconjugates |
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2014
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| WO2015095301A3 (en) | 2015-09-03 |
| AU2014364812A1 (en) | 2016-07-07 |
| CN105899526A (zh) | 2016-08-24 |
| US20180244717A1 (en) | 2018-08-30 |
| US20190382441A1 (en) | 2019-12-19 |
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| US10787480B2 (en) | 2020-09-29 |
| CA2930614A1 (en) | 2015-06-25 |
| BR112016012538A2 (pt) | 2017-09-26 |
| JP2017503777A (ja) | 2017-02-02 |
| ES2758506T3 (es) | 2020-05-05 |
| US20160311853A1 (en) | 2016-10-27 |
| SG11201604877UA (en) | 2016-07-28 |
| PT3082877T (pt) | 2019-12-03 |
| EA201691251A1 (ru) | 2016-11-30 |
| PL3082877T3 (pl) | 2020-02-28 |
| KR20160098257A (ko) | 2016-08-18 |
| EP3082877A2 (en) | 2016-10-26 |
| EP3082877B1 (en) | 2019-08-28 |
| US10392421B2 (en) | 2019-08-27 |
| IL245558B (en) | 2020-01-30 |
| EP3753578A1 (en) | 2020-12-23 |
| WO2015095301A2 (en) | 2015-06-25 |
| JP2020023514A (ja) | 2020-02-13 |
| IL245558A0 (en) | 2016-06-30 |
| US9988420B2 (en) | 2018-06-05 |
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