EA027925B1 - Ендиины, их конъюгаты и способы их получения и применения - Google Patents
Ендиины, их конъюгаты и способы их получения и применения Download PDFInfo
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- EA027925B1 EA027925B1 EA201491447A EA201491447A EA027925B1 EA 027925 B1 EA027925 B1 EA 027925B1 EA 201491447 A EA201491447 A EA 201491447A EA 201491447 A EA201491447 A EA 201491447A EA 027925 B1 EA027925 B1 EA 027925B1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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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| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| SG11201601047SA (en) * | 2013-08-14 | 2016-03-30 | Univ Rice William M | Derivatives of uncialamycin, methods of synthesis and their use as antitumor agents |
| SG11201607818WA (en) | 2014-03-20 | 2016-10-28 | Bristol Myers Squibb Co | Stabilized fibronectin based scaffold molecules |
| SMT202000413T1 (it) | 2014-11-21 | 2020-09-10 | Bristol Myers Squibb Co | Anticorpi nei confronti di cd73 e loro usi |
| MX386942B (es) | 2014-11-21 | 2025-03-19 | Bristol Myers Squibb Co | Anticuerpos que comprenden regiones constantes pesadas modificadas. |
| AU2015353573B2 (en) | 2014-11-25 | 2020-09-03 | Bristol-Myers Squibb Company | Novel PD-L1 binding polypeptides for imaging |
| CN107531720A (zh) * | 2015-01-08 | 2018-01-02 | 斯克利普斯研究院 | 抗癌症候选药物 |
| EP3268048B1 (en) | 2015-03-10 | 2019-05-08 | Bristol-Myers Squibb Company | Antibodies conjugatable by transglutaminase and conjugates made therefrom |
| PT3303396T (pt) | 2015-05-29 | 2023-01-30 | Bristol Myers Squibb Co | Anticorpos contra ox40 e utilizações dos mesmos |
| JP6951340B2 (ja) | 2015-09-23 | 2021-10-20 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | グリピカン−３結合フィブロネクチンベース足場分子 |
| CN107029242A (zh) | 2015-11-03 | 2017-08-11 | 财团法人工业技术研究院 | 抗体药物复合物及其制造方法 |
| AU2016377371A1 (en) | 2015-12-21 | 2018-08-09 | Bristol-Myers Squibb Company | Variant antibodies for site-specific conjugation |
| KR20230038311A (ko) | 2016-03-04 | 2023-03-17 | 브리스톨-마이어스 스큅 컴퍼니 | 항-cd73 항체와의 조합 요법 |
| CN106267188B (zh) * | 2016-08-15 | 2025-06-17 | 深圳大学 | 小分子免疫激动剂偶联pd-1抗体的新型抗体及其在抗肿瘤中的应用 |
| US20190218294A1 (en) | 2016-09-09 | 2019-07-18 | Bristol-Myers Squibb Company | Use of an anti-pd-1 antibody in combination with an anti-mesothelin antibody in cancer treatment |
| US10738338B2 (en) | 2016-10-18 | 2020-08-11 | The Research Foundation for the State University | Method and composition for biocatalytic protein-oligonucleotide conjugation and protein-oligonucleotide conjugate |
| JP7762498B2 (ja) | 2017-05-25 | 2025-10-30 | ブリストル－マイヤーズ スクイブ カンパニー | 修飾重鎖定常領域を含む抗体 |
| CN111683686A (zh) * | 2017-12-06 | 2020-09-18 | 西纳福克斯股份有限公司 | 烯二炔缀合物 |
| CN110183659B (zh) * | 2018-02-21 | 2022-04-26 | 香港科技大学 | 含有杂环的聚合物、其制备方法及其应用 |
| WO2020112781A1 (en) | 2018-11-28 | 2020-06-04 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
| DK3886914T3 (da) | 2018-11-30 | 2023-07-03 | Bristol Myers Squibb Co | Antistof omfattende en glutaminholdig letkæde-c-terminal forlængelse, konjugater deraf og fremgangsmåder samt anvendelser |
| US12478686B2 (en) | 2018-12-12 | 2025-11-25 | Bristol-Myers Squibb Company | Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses |
| AU2020279478A1 (en) * | 2019-05-22 | 2021-12-09 | Board Of Regents, The University Of Texas System | Functionalized gold carbene naphthoquinone complexes for use in the treatment of cancer |
| US20240377413A1 (en) | 2019-09-16 | 2024-11-14 | Bristol-Myers Squibb Company | Dual capture method for analysis of antibody-drug conjugates |
| CA3223936A1 (en) | 2021-06-28 | 2023-01-05 | Ronald Christiaan Elgersma | Conjugates comprising phosphoantigens and their use in therapy |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0484856A2 (en) * | 1990-11-05 | 1992-05-13 | Bristol-Myers Squibb Company | Dynemicin C antitumor antibiotic |
| WO1993023046A1 (en) * | 1992-05-21 | 1993-11-25 | The Scripps Research Institute | Enantiomeric cynemicin analogs, preparation and use thereof |
| WO2007038868A2 (en) * | 2005-10-03 | 2007-04-12 | The University Of British Columbia | Novel enediyne compound and uses thereof |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1981001145A1 (en) | 1979-10-18 | 1981-04-30 | Univ Illinois | Hydrolytic enzyme-activatible pro-drugs |
| 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 |
| US4631190A (en) | 1981-06-26 | 1986-12-23 | Shen Wei C | Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers |
| US5144011A (en) | 1981-06-26 | 1992-09-01 | Boston University | Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers |
| US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| 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 |
| US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
| US4698420A (en) | 1985-02-25 | 1987-10-06 | Xoma Corporation | Antibody hybrid molecules and process for their preparation |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
| MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| US6955811B2 (en) | 1997-11-07 | 2005-10-18 | Trillium Therapeutics Inc. | Methods of inhibiting immune response suppression by administering antibodies to OX-2 |
| JP4093757B2 (ja) | 1999-08-24 | 2008-06-04 | メダレックス， インコーポレイテッド | ヒトｃｔｌａ−４抗体およびその使用 |
| IL154183A0 (en) | 2001-05-31 | 2003-07-31 | Medarex Inc | Cytotoxins, prodrugs, linkers and stabilizers useful therefor |
| US7091186B2 (en) | 2001-09-24 | 2006-08-15 | Seattle Genetics, Inc. | p-Amidobenzylethers in drug delivery agents |
| KR100668538B1 (ko) | 2002-01-09 | 2007-01-16 | 메다렉스, 인코포레이티드 | Ｃｄ３０에 대한 인간 모노클로날 항체 |
| EP2261244A3 (en) | 2003-04-15 | 2011-02-23 | Glaxosmithkline LLC | Human il-18 substitution mutants and their conjugates |
| TWI353992B (en) | 2003-07-22 | 2011-12-11 | Schering Ag | Rg1 antibodies and uses thereof |
| WO2005051976A2 (en) | 2003-11-20 | 2005-06-09 | Ansata Therapeutics, Inc. | Protein and peptide ligation processes and one-step purification processes |
| US8170637B2 (en) * | 2008-05-06 | 2012-05-01 | Neurosky, Inc. | Dry electrode device and method of assembly |
| EP1718667B1 (en) | 2004-02-23 | 2013-01-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
| JP4806680B2 (ja) | 2004-05-19 | 2011-11-02 | メダレックス インコーポレイテッド | 自己犠牲リンカー及び薬剤複合体 |
| RU2402548C2 (ru) | 2004-05-19 | 2010-10-27 | Медарекс, Инк. | Химические линкеры и их конъюгаты |
| BRPI0516284A (pt) | 2004-09-23 | 2008-09-02 | Genentech Inc | anticorpo construìdo com cisteìna, método de selecionar anticorpos, compostos conjugados de droga-anticorpo, composição farmacêutica, método para matar ou inibir a proliferação de células de tumor, métodos de inibir a proliferação celular e o crescimento de células de tumor, artigo manufaturado e método para produzir um composto |
| US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
| CA2970873C (en) | 2005-05-09 | 2022-05-17 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics |
| MX2007015944A (es) | 2005-06-20 | 2008-03-07 | Medarex Inc | Anticuerpos cd19 y sus usos. |
| EA016186B1 (ru) | 2005-09-26 | 2012-03-30 | Медарекс, Инк. | Человеческие моноклональные антитела к cd70 и их применение |
| NZ566982A (en) | 2005-09-26 | 2011-06-30 | Medarex Inc | Duocarmycin drug conjugates |
| CN101365679B (zh) | 2005-10-26 | 2012-11-14 | 梅达莱克斯公司 | 制备cc-1065类似物的方法和化合物 |
| WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
| CN101360761B (zh) | 2005-12-08 | 2012-09-12 | 米德列斯公司 | 抗蛋白质酪氨酸激酶7（ptk7）的人单克隆抗体及其用途 |
| SG170080A1 (en) | 2005-12-08 | 2011-04-29 | Medarex Inc | Human monoclonal antibodies to o8e |
| KR100869414B1 (ko) | 2005-12-13 | 2008-11-21 | 야마하 가부시키가이샤 | 건반식 음판 타악기용의 음판 및 그 제조방법, 음판타악기의 음원 유닛 및 건반식 타악기 |
| MX2009002524A (es) | 2006-09-08 | 2009-06-22 | Ambrx Inc | Incorporacion especifica de sitio de aminoacidos no naturales por celulas de vertebrados. |
| ES2678060T3 (es) | 2006-12-01 | 2018-08-08 | E. R. Squibb & Sons, L.L.C. | Anticuerpos, en particular, anticuerpos humanos, que se unen a CD22 y usos de los mismos |
| UY30776A1 (es) | 2006-12-21 | 2008-07-03 | Medarex Inc | Anticuerpos cd44 |
| TWI412367B (zh) | 2006-12-28 | 2013-10-21 | Medarex Llc | 化學鏈接劑與可裂解基質以及其之綴合物 |
| AR065404A1 (es) | 2007-02-21 | 2009-06-03 | Medarex Inc | Conjugados farmaco-ligando, los que se unen a citotoxinas potentes, composicion farmaceutica que los contienen y su uso para retardar o detener el crecimiento de un tumor en un mamifero |
| EP2185188B1 (en) | 2007-08-22 | 2014-08-06 | Medarex, L.L.C. | Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions |
| RS53760B1 (sr) | 2007-10-01 | 2015-06-30 | Bristol-Myers Squibb Company | Humana antitela koja se vezuju za mezotelin i njihove upotrebe |
| EP2391714B2 (en) | 2009-01-30 | 2019-07-24 | Whitehead Institute for Biomedical Research | Methods for ligation and uses thereof |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0484856A2 (en) * | 1990-11-05 | 1992-05-13 | Bristol-Myers Squibb Company | Dynemicin C antitumor antibiotic |
| WO1993023046A1 (en) * | 1992-05-21 | 1993-11-25 | The Scripps Research Institute | Enantiomeric cynemicin analogs, preparation and use thereof |
| WO2007038868A2 (en) * | 2005-10-03 | 2007-04-12 | The University Of British Columbia | Novel enediyne compound and uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| K. C. NICOLAOU, JASON S. CHEN, HONGJUN ZHANG, ANA MONTERO: "Asymmetric synthesis and biological properties of Uncialamycin and 26-epi-Uncialamycin", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, WILEY-VCH VERLAG GMBH, vol. 47, 17 December 2007 (2007-12-17), pages 185 - 189, XP002694366, ISSN: 1433-7851, DOI: 10.1002/anie.200704577 * |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): RU |