KR102493853B1 - 세코-시클로프로파피롤로인돌 화합물, 그의 항체-약물 접합체, 및 제조 및 사용 방법 - Google Patents

세코-시클로프로파피롤로인돌 화합물, 그의 항체-약물 접합체, 및 제조 및 사용 방법 Download PDF

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KR102493853B1
KR102493853B1 KR1020197007464A KR20197007464A KR102493853B1 KR 102493853 B1 KR102493853 B1 KR 102493853B1 KR 1020197007464 A KR1020197007464 A KR 1020197007464A KR 20197007464 A KR20197007464 A KR 20197007464A KR 102493853 B1 KR102493853 B1 KR 102493853B1
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KR20190039570A (ko
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푸캉 양
치안 장
로렌스 비. 스나이더
산지브 강과르
데일 엘. 보거
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브리스톨-마이어스 스큅 컴퍼니
더 스크립스 리서치 인스티튜트
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • 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
    • A61K39/44—Antibodies bound to carriers
    • 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
    • A—HUMAN NECESSITIES
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    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
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    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6857—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from lung cancer cell
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6863—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6869—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], 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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  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Oncology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pulmonology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
KR1020197007464A 2016-08-19 2017-08-18 세코-시클로프로파피롤로인돌 화합물, 그의 항체-약물 접합체, 및 제조 및 사용 방법 Active KR102493853B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662377052P 2016-08-19 2016-08-19
US62/377,052 2016-08-19
PCT/US2017/047465 WO2018035391A1 (en) 2016-08-19 2017-08-18 Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use

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KR20190039570A KR20190039570A (ko) 2019-04-12
KR102493853B1 true KR102493853B1 (ko) 2023-01-30

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US (1) US10287291B2 (https=)
EP (1) EP3500574B1 (https=)
JP (1) JP7023933B2 (https=)
KR (1) KR102493853B1 (https=)
CN (1) CN109641911B (https=)
ES (1) ES2902179T3 (https=)
WO (1) WO2018035391A1 (https=)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102861586B1 (ko) 2018-11-30 2025-09-17 브리스톨-마이어스 스큅 컴퍼니 글루타민-함유 경쇄 c-말단 연장부를 포함하는 항체, 그의 접합체, 및 방법 및 용도
US12478686B2 (en) 2018-12-12 2025-11-25 Bristol-Myers Squibb Company Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses
WO2021055306A1 (en) 2019-09-16 2021-03-25 Bristol-Myers Squibb Company Dual capture method for analysis of antibody-drug conjugates
CA3234692A1 (en) * 2021-09-30 2023-04-06 Ajinomoto Co., Inc. Conjugate of antibody and functional substance or salt thereof, and antibody derivative and compound used in production of the same or salts thereof
MX2024009740A (es) * 2022-02-11 2024-08-19 Shenzhen Enduring Biotech Ltd Conjugado de anticuerpo-farmaco pegilado que contiene grupos hidroxilo.

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007103288A2 (en) 2006-03-02 2007-09-13 Seattle Genetics, Inc. Engineered antibody drug conjugates
US20130030166A1 (en) 2011-07-26 2013-01-31 Elitech Holding B.V. Minor groove binder phosphoramidites and methods of use
CN104220442A (zh) 2012-04-05 2014-12-17 内尔维阿诺医学科学有限公司 新的烷化剂

Family Cites Families (78)

* Cited by examiner, † Cited by third party
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.
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
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
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
US5091541A (en) * 1990-02-01 1992-02-25 Hoechst-Roussel Pharmaceuticals Inc. Hexahydropyrrolo(2,3-B)indole carbamates, ureas, amides and related compounds
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
AU727608B2 (en) 1995-10-03 2000-12-14 Scripps Research Institute, The CBI analogs of CC-1065 and the duocarmycins
NZ500789A (en) 1997-05-22 2002-05-31 Scripps Research Inst Analogs of duocarmycin and CC-1065
US7425541B2 (en) 1998-12-11 2008-09-16 Medarex, Inc. Enzyme-cleavable prodrug compounds
EP1212422B1 (en) 1999-08-24 2007-02-21 Medarex, Inc. Human ctla-4 antibodies and their uses
AU2001286727A1 (en) 2000-08-24 2002-03-04 Coulter Pharmaceutical, Inc. Prodrugs activated by plasmin and their use in cancer chemotherapy
US6989452B2 (en) 2001-05-31 2006-01-24 Medarex, Inc. Disulfide prodrugs and linkers and stabilizers useful therefor
WO2002100353A2 (en) 2001-06-11 2002-12-19 Medarex, Inc. Cd10-activated prodrug compounds
US7091186B2 (en) 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
IL162835A0 (en) 2002-01-09 2005-11-20 Medarex Inc Human monoclonal antibodies against cd30
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
EP2261244A3 (en) 2003-04-15 2011-02-23 Glaxosmithkline LLC Human il-18 substitution mutants and their conjugates
MXPA06000798A (es) 2003-07-22 2006-04-07 Schering Ag Anticuerpos de rg1 y usos de los mismos.
WO2005051976A2 (en) 2003-11-20 2005-06-09 Ansata Therapeutics, Inc. Protein and peptide ligation processes and one-step purification processes
PL1691837T3 (pl) 2003-12-10 2012-11-30 Squibb & Sons Llc IP-10 przeciwciała i ich zastosowanie
CA2556752C (en) 2004-02-23 2016-02-02 Genentech, Inc. Heterocyclic self-immolative linkers and conjugates
US7691962B2 (en) 2004-05-19 2010-04-06 Medarex, Inc. Chemical linkers and conjugates thereof
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
DK1791565T3 (en) 2004-09-23 2016-08-01 Genentech Inc Cysteingensplejsede antibodies and conjugates
CN101160324B (zh) 2005-02-18 2013-04-24 米德列斯公司 缺乏岩藻糖残基的抗前列腺特异性膜抗原(psma)单克隆抗体
JP2008529556A (ja) 2005-02-18 2008-08-07 メダレックス， インク． 前立腺特異的膜抗原（ｐｓｍａ）に対するヒトモノクローナル抗体
US7714016B2 (en) 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
DK2439273T3 (da) 2005-05-09 2019-06-03 Ono Pharmaceutical Co Humane monoklonale antistoffer til programmeret død-1(pd-1) og fremgangsmåder til behandling af cancer ved anvendelse af anti-pd-1- antistoffer alene eller i kombination med andre immunterapeutika
PT1907424E (pt) 2005-07-01 2015-10-09 Squibb & Sons Llc Anticorpos monoclonais humanos para o ligando 1 de morte programada (pd-l1)
DK3248613T3 (da) 2005-07-18 2022-03-14 Seagen Inc Beta-glucuronid-lægemiddel-linkerkonjugater
NZ566395A (en) 2005-09-26 2012-03-30 Medarex Inc Human monoclonal antibodies to CD70
EP2354163A3 (en) 2005-09-26 2013-04-24 Medarex, Inc. Conjugates of duocarmycin and anti-CD70 or anti-PSMA antibodies
RS52100B (sr) 2005-10-26 2012-06-30 Medarex, Inc. Postupci i jedinjenja za pripremu analoga cc-1065
WO2007059404A2 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
EA017812B1 (ru) 2005-12-08 2013-03-29 Медарекс, Инк. Выделенное моноклональное антитело или его антигенсвязывающий участок, которые связываются с протеинтирозинкиназой 7 ( ptk7) человека, и их применение
US8383118B2 (en) 2005-12-08 2013-02-26 Medarex, Inc. Human monoclonal antibodies to fucosyl-GM1 and methods for using anti-fucosyl-GM1
WO2007067991A2 (en) 2005-12-08 2007-06-14 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
WO2008066583A2 (en) 2006-06-29 2008-06-05 The Board Of Trustees Of The Leland Stanford Junior University Cell-free synthesis of proteins containing unnatural amino acids
WO2008020075A1 (en) 2006-08-18 2008-02-21 Novo Nordisk Health Care Ag Transglutaminase variants with improved specificity
JP2010502221A (ja) 2006-09-08 2010-01-28 アンブルックス，インコーポレイテッド 脊椎動物細胞による非天然アミノ酸の部位特異的組み込み
MX2009003306A (es) 2006-10-02 2009-04-23 Medarex Inc Anticuerpos humanos que se unen a cxcr4 y sus usos.
EP2083816A2 (en) * 2006-10-27 2009-08-05 Brystol-Myers Squibb Company Heterocyclic amide compounds useful as kinase inhibitors
US8481683B2 (en) 2006-12-01 2013-07-09 Medarex, Inc. Human antibodies that bind CD22 and uses thereof
UY30776A1 (es) 2006-12-21 2008-07-03 Medarex Inc Anticuerpos cd44
TWI412367B (zh) 2006-12-28 2013-10-21 梅達雷克斯有限責任公司 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
US20100087371A1 (en) 2007-02-22 2010-04-08 Sean Hu Transglutaminase Variants with Improved Specificity
US7723343B2 (en) * 2007-03-30 2010-05-25 King Pharmaceuticals Research And Development, Inc. Adenosine A2A receptor antagonists
ME02345B (me) 2007-07-17 2016-08-31 Squibb & Sons Llc MONOKLONSKA ANTlTELA PROTIV GLIPIKANA-3
US8865875B2 (en) 2007-08-22 2014-10-21 Medarex, L.L.C. Site-specific attachment of drugs or other agents to engineered antibodies with C-terminal extensions
ES2526355T3 (es) 2007-10-01 2015-01-09 Bristol-Myers Squibb Company Anticuerpos humanos que se adhieren a mesotelina, y usos de los mismos
WO2010087994A2 (en) 2009-01-30 2010-08-05 Whitehead Institute For Biomedical Research Methods for ligation and uses thereof
US8394922B2 (en) 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
WO2011103557A1 (en) 2010-02-22 2011-08-25 Advanced Cancer Therapeutics, Llc Small molecule inhibitors of pfkfb3 and glycolytic flux and their methods of use as anti-cancer therapeutics
PT3056203T (pt) 2010-04-21 2018-02-15 Syntarga Bv Conjugados de análogos de cc-1065 e ligantes bifuncionais
CA2813411C (en) 2010-11-05 2016-08-02 Rinat Neuroscience Corporation Engineered polypeptide conjugates and methods for making thereof using transglutaminase
US8852599B2 (en) 2011-05-26 2014-10-07 Bristol-Myers Squibb Company Immunoconjugates, compositions for making them, and methods of making and use
CN102520153A (zh) * 2011-12-15 2012-06-27 安徽师范大学 一种快速检测食品中的邻苯二甲酸二丁酯的方法
LT2956173T (lt) 2013-02-14 2017-06-26 Bristol-Myers Squibb Company Tubulizino junginiai, gavimo ir panaudojimo būdai
JP6574754B2 (ja) 2013-03-19 2019-09-11 ベイジン シェノゲン ファーマ グループ リミテッド エストロゲン受容体関連疾患を処置するための抗体及び方法
US9765077B2 (en) * 2015-05-29 2017-09-19 University Of East Anglia Synthesis of duocarmycin analogues

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007103288A2 (en) 2006-03-02 2007-09-13 Seattle Genetics, Inc. Engineered antibody drug conjugates
US20130030166A1 (en) 2011-07-26 2013-01-31 Elitech Holding B.V. Minor groove binder phosphoramidites and methods of use
CN104220442A (zh) 2012-04-05 2014-12-17 内尔维阿诺医学科学有限公司 新的烷化剂

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