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KR900007408A - 향체-약물 결합체 - Google Patents

향체-약물 결합체 Download PDF

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Publication number
KR900007408A
KR900007408A KR1019890016191A KR890016191A KR900007408A KR 900007408 A KR900007408 A KR 900007408A KR 1019890016191 A KR1019890016191 A KR 1019890016191A KR 890016191 A KR890016191 A KR 890016191A KR 900007408 A KR900007408 A KR 900007408A
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South Korea
Prior art keywords
carboxylic acid
formula
drug
antibody
conjugate
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KR1019890016191A
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래번 바튼 러셀
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레로이 위타커
일라이 릴리 앤드 캄파니
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • A61K47/6883—Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and unsaturated
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

내용 없음

Description

항체-약물 결합체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (16)

  1. 일반식(Ⅰ)의 약물 결합체.
    상기식에서, Ab는 약물의 수송이 요구되는 세포에 결합된 항원을 인지하는 항체 또는 이의 항원-인지 단편이고, Q는 -NH-, -O-, 또는 -S-이며, R-Q-는 반응적으로-이용 가능한 아미노, 히이드록시 또는 티올작용을 갖는 약물의 잔기이고, R1은 카복실산 보호 그룹이며, Y는 -O-, -NH-, NCH3-, 또는 -NC2H5-이고, n은 1내지 약8의 정수이며, m은 1내지 약 10의 정수이다.
  2. 제1항에 있어서, 약물이 일반식(Ⅴ),(Ⅵ),(Ⅶ),(Ⅷ),(Ⅸ),(Ⅹ),(ⅩⅠ),(ⅩⅡ),(ⅩⅢ),(ⅩⅣ)중 어느 하나의 세포 특성 약물인 결합체.
    (ⅩⅡ),(ⅩⅢ),(ⅩⅣ)중 어느 하나의 세포 특성 약물인 결합체.
    상기식에서, R5는 수소 또는 하이드록시이고, R6는 아미노 또는 하이드록시이며, R7, R10및 R13은 수소 또는 메틸이고, R8는 수소, 플루오로, 클로로, 브로모, 또는 요오드이며, R9은 하이드록시 또는 카복실산의 염을 완성시키는 잔기이고,
    R11은 아미노 C1-C3알킬아미노, 디(C1-C3알킬)-아미노 또는 C4-C6폴리메틸렌 아미노이며, R12잔기중 하나는 결합이고 다른 잔기들은 수소이며, R14는 메틸 또는 티에닐이고, R15는 H, CH3또는 CHO이며, R17및R18이 각각 독립적으로는 R18은 수소이고, R16및 R17중 하나는 에틸이며, 다른 하나는 H 또는 OH이고 R17및 R18이 이들이 결한된 탄소와 함께는 R17및 R18은 R16이 에틸인 옥시란 환을 형성하며, R19는 수소, (C1-C3알킬)-CO, 또는 클로로 치환된 (C1-C3알킬)-CO이고, p는 0또는 1이며, R20은 결합이거나 (C2-C4알킬)-X(여기에서, X는 -O-, -S- 또는 -NH-이다)이고, │←R21은 하기 일반식(여기에서, R22는 수소, 메틸, 브로모, 플루오르, 클로로 또는 요오드이고, R23은 -OH12또는 -NHR12이며, R24는 수소, 브리모, 클로로, 또는 요오드이다)
    중 어느 하나의 염기이다 ;
  3. 제1항 또는 제2항에 있어서, 항체가 모노클로날 항체인 결합체,
  4. 제1항 내지 3항중 어느 한 항에 있어서, m이 약 3내지 약8인 결합체.
  5. 제1항 내지 4항중 어느 한 항에 있어서, n이 1내지 약 6인 결합체.
  6. 제5항에 있어서, n이 1내지 약 3인 결합체.
  7. 제1항 내지 6항중 어느 한 항에 있어서, 약물이 일반식(Ⅴ),(Ⅵ) 또는(ⅩⅢ)인 결합체.
  8. 비경구적으로 투여 가능한 매질 및 제1항 내지 7항중 어느 한항에 따른 결합체를 함유한 약제학적 조성물.
  9. 제1항 내지 7항중 어느 한 항에 있어서, 약제로 사용하기 위한 결합체.
  10. (A)일반식(Ⅲ)의 변형된 항체를 일반식(A)의 약물과 반응시키거나, (B) 일반식(Ⅳ)의 약물 유도체를 제1항에 정의된 Ab의 항체 또는 항체 단편과 반응시킴을 특징으로 하여, 제1항 내지 7항중 어느 한 항에 따른 일반식(Ⅰ)의 약물 결합체를 제조하는 방법.
    상기식에서 R1, Y, n, m, Ab, Q 및 R-Q-는 제1항에서 정의한 바와 같고, R4는 C1-C4알콕시이며, R3는 하이드록시, 카복실산 활성화 그룹, 또는 카복실 산의 염을 완성시키는 잔기이다.
  11. 일반식(Ⅱ)의 말로네이트
    n 및 Y는 제1항에서 정의한 바와 같고, R2는 하이드록시, 카복실산 보호 그룹 또는 카복실산의 염을 완성시키는 잔기이며, R3는 하이드록시, 카복실산 보호 그룹, 키복실산 활성화 그룹, 또는 카복실산의 염을 완성시키는 잔기이고, R4는 C1-C4알콕시이다.
  12. 제11항에 있어서, R2가 카복실산 보호 그룹이고, R3가 카복실산 보호 그룹 또는 카복실산 활성화 그룹이며, n이 1내지 약 6인 말로네이트.
  13. 일반식 (Ⅲ)의 변형된 항체 또는 항체 단면.
    상기식에서, R1, Y, n, m, Ab, 제1항에서 정의한 바와 같고, R4는 C1-C4알콕시이다.
  14. 일반식(Ⅳ)의 약물 유도체
    상기식에서, Q,R-Q-, R', Y 및 n은 제1항에서 정의한 바와 같고, R3는 하이드록시, 카복실산 보호그룹, 카복실산 활성화 그룹, 또는 카복실산의 염을 완성시키는 잔기이다.
  15. 일반식(Ⅱ)의 말로네이트를 제1항에 정의된 Ab의 항체 도는 항체 단편과 반응시킴을 특징으로 하여, 제13항에서 정의한 바와 같은 일반식(Ⅲ)의 변형된 항체 또는 항체 단편을 제조하는 방법.
    상기 식에서, Y 및 n은 제1항에서 정의한 바와 같고, R2는 카복실산 보호 그룹이며, R3는 하이드록시, 카복실산 활성화 그룹, 또는 카복실산의 염을 완성시키는 잔기이고, R4는 C1-C4알콕시이다.
  16. 일반식(Ⅱ)의 말로네이트를 일반식(A)의 약물과 반응시킴을 특징으로 하여, 제14항에 정의한 바와 같은 일반식(Ⅳ)의 약물 유도체를 제조하는 방법.
    상기 식에서, R2는 카복실산 보호 그룹이고, R4, Y, n 및 R3는 제12항에서 정의한 바와 같고, Q 및 R-Q는 제1항에서 정의한 바와 같다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019890016191A 1988-11-10 1989-11-09 향체-약물 결합체 Ceased KR900007408A (ko)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/269,815 US5010176A (en) 1988-11-10 1988-11-10 Antibody-drug conjugates
US07/269,815 1988-11-10

Publications (1)

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KR900007408A true KR900007408A (ko) 1990-06-01

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US (2) US5010176A (ko)
EP (1) EP0368668B1 (ko)
JP (1) JPH02191300A (ko)
KR (1) KR900007408A (ko)
CN (1) CN1042546A (ko)
AU (1) AU619614B2 (ko)
CA (1) CA2000483A1 (ko)
DE (1) DE68927610T2 (ko)
DK (1) DK556689A (ko)
ES (1) ES2095840T3 (ko)
FI (1) FI895283A7 (ko)
HU (1) HU210147B (ko)
IL (1) IL92230A0 (ko)
NZ (1) NZ231302A (ko)
PT (1) PT92213B (ko)
ZA (1) ZA898434B (ko)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA914625B (en) * 1990-06-22 1993-02-24 Lilly Co Eli In vivo targeting with bifunctional antibodies
ES2049656B1 (es) * 1992-10-08 1994-11-16 Lilly Co Eli Grupos de conjugados de farmacos con anticuerpos.
US5556623A (en) * 1993-03-30 1996-09-17 Eli Lilly And Company Antibody-drug conjugates
JPH072895A (ja) * 1993-04-28 1995-01-06 Eli Lilly & Co 抗体−薬物複合体
US20030119724A1 (en) * 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
US6521431B1 (en) 1999-06-22 2003-02-18 Access Pharmaceuticals, Inc. Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments
CN1110322C (zh) * 1999-07-21 2003-06-04 中国医学科学院医药生物技术研究所 单克隆抗体Fab'－平阳霉素偶联物及其抗肿瘤作用
AU2002217980A1 (en) 2000-12-01 2002-06-11 Cell Works Inc. Conjugates of glycosylated/galactosylated peptide
US6441163B1 (en) 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
FR2862134B1 (fr) * 2003-11-12 2007-07-27 Sebia Sa Analyse et typage de proteines monoclonales par electrophorese capillaire et immunodeplacement
DE102006037786A1 (de) 2006-08-11 2008-03-20 Resprotect Gmbh Nukleoside, diese enthaltendes Arzneimittel und deren Verwendung
US7825267B2 (en) * 2006-09-08 2010-11-02 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Synthesis of FR901464 and analogs with antitumor activity
CA3128656A1 (en) 2007-08-22 2009-02-26 The Regents Of The University Of California Activatable binding polypeptides and methods of identification and use thereof
EP2042496A1 (de) 2007-09-18 2009-04-01 Bayer CropScience AG Verfahren zur Herstellung von 4-Aminobut-2-enoliden
CN102482347B (zh) 2009-01-12 2017-04-26 希托马克斯医疗有限责任公司 修饰抗体组合物及其制备和使用方法
CN102481341B (zh) 2009-02-23 2017-05-17 希托马克斯医疗有限公司 蛋白原及其使用方法
WO2014100367A1 (en) 2012-12-21 2014-06-26 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Synthesis of fr901464 and analogs with antitumor activity
ES2877548T3 (es) 2016-06-02 2021-11-17 Abbvie Inc Agonista del receptor de glucocorticoides e inmunoconjugados del mismo
PH12020550779A1 (en) 2017-12-01 2021-04-19 Abbvie Inc Glucocorticoid receptor agonist and immunoconjugates thereof
CN114874214B (zh) * 2022-05-31 2023-03-21 南京航空航天大学 可偶联巯基的双功能大环螯合剂衍生物及其制备方法

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3905871A (en) * 1971-05-14 1975-09-16 Syva Co Lactam conjugates to enzymes
DE2635841C2 (de) * 1976-08-10 1983-02-24 Dynamit Nobel Ag, 5210 Troisdorf Verfahren zur Herstellung von Alkoxymethylenmalonsäurenitrilen
US4230805A (en) * 1977-04-15 1980-10-28 Syva Company Theophylline antigens and antibodies
US4631190A (en) * 1981-06-26 1986-12-23 Shen Wei C Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers
US4671958A (en) * 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
GB2137210B (en) * 1983-03-30 1986-11-19 Lilly Industries Ltd Immunoglobulin conjugates
GB2181126B (en) * 1983-03-30 1987-08-26 Lilly Industries Ltd Novel pharmaceutical compounds
US4695624A (en) * 1984-05-10 1987-09-22 Merck & Co., Inc. Covalently-modified polyanionic bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins with bigeneric spacers, and methods of preparing such polysaccharides and conjugates and of confirming covalency
US4764368A (en) * 1984-08-29 1988-08-16 Dana-Farber Cancer Institute, Inc. Acid-cleavable compound
US4762915A (en) * 1985-01-18 1988-08-09 Liposome Technology, Inc. Protein-liposome conjugates
GB8610551D0 (en) * 1986-04-30 1986-06-04 Hoffmann La Roche Polypeptide & protein derivatives
ZA873600B (en) * 1986-05-27 1988-12-28 Lilly Co Eli Immunoglobulin conjugates
US4997913A (en) * 1986-06-30 1991-03-05 Oncogen pH-sensitive immunoconjugates and methods for their use in tumor therapy
US4793986A (en) * 1987-02-25 1988-12-27 Johnson Matthey, Inc. Macromolecular platinum antitumor compounds
US5028697A (en) * 1988-08-08 1991-07-02 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized methotrexate analogs via simple organic linkers
GB8903021D0 (en) * 1989-02-10 1989-03-30 Celltech Ltd Chemical compounds

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AU619614B2 (en) 1992-01-30
EP0368668B1 (en) 1997-01-02
HUT53126A (en) 1990-09-28
FI895283A7 (fi) 1990-05-11
EP0368668A3 (en) 1992-10-07
DE68927610D1 (de) 1997-02-13
CA2000483A1 (en) 1990-05-10
NZ231302A (en) 1992-11-25
US5514794A (en) 1996-05-07
HU895847D0 (en) 1990-01-28
ZA898434B (en) 1991-07-31
DK556689A (da) 1990-05-14
FI895283A0 (fi) 1989-11-07
IL92230A0 (en) 1990-07-26
JPH02191300A (ja) 1990-07-27
ES2095840T3 (es) 1997-03-01
AU4451389A (en) 1990-06-28
EP0368668A2 (en) 1990-05-16
PT92213B (pt) 1995-07-06
CN1042546A (zh) 1990-05-30
HU210147B (en) 1995-02-28
DK556689D0 (da) 1989-11-08
PT92213A (pt) 1990-05-31
DE68927610T2 (de) 1997-05-15
US5010176A (en) 1991-04-23

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