KR900002804A - 세포독성 약물 결합체 및 이의 제조방법 - Google Patents
세포독성 약물 결합체 및 이의 제조방법 Download PDFInfo
- Publication number
- KR900002804A KR900002804A KR1019890011217A KR890011217A KR900002804A KR 900002804 A KR900002804 A KR 900002804A KR 1019890011217 A KR1019890011217 A KR 1019890011217A KR 890011217 A KR890011217 A KR 890011217A KR 900002804 A KR900002804 A KR 900002804A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- phenyl
- antibody
- carbonyl
- bond
- Prior art date
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Classifications
-
- 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
- A61K47/6835—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
- 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
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Mycology (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)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (10)
- 일반식(Ⅰ)의 세포독성 약물 결합체.상기식에서, Ab는 목적하지 않는 세포와 결합한 항원을 인지하는 생리학적으로 허용되는 항체 또는 이의 항원-인지 단편이고, m은 1 내지 약 10의 정수이며, Z는 수소 또는 C1-C3비측쇄 알킬이고, X는 결합, C1-C4알킬렌, C2-C4알케닐렌 또는 아미노-C1-C4알킬렌이며, Y는 결합, 카보닐, -O-, -S- 또는 설포닐이고, 단, X가 아미노알킬렌일 경우, Y는 카보닐 또는 설포닐이고, X가 결합인 경우, Y는 결합 또는 카보닐이며, Ar은 피롤릴, m-페닐 또는 p-페닐(여기에서, 페닐그룹은 브로모, 클로로, 플루오로, 메톡시, 니트로 또는 C1-C3알킬로 일- 또는 이치환될 수 있다)이고, Ⅴ는 일반식(Ⅱ)의 빈카 약물이다.(여기에서, R은 H, CH3또는 CHO이고 ; R2및 R3가 단독으로 존재할 경우, R3는 H이고, R1및 R2중의 하나는 에틸이고 다른 하나는 H 또는 OH이며 ; R2및 R3가 이들이 결합하고 있는 탄소와 함께 존재할 경우, 이들은 R1이 에틸인 옥시란 환을 형성하고 ; R4는 H, (C1-C3알킬)-CO 또는 클로로 치환된 (C1-C3알킬)-CO이다.)
- 제 1 항에 있어서, 항체 또는 이의 단편이 암세포를 인지하는 결합체.
- 제 1 항 또는 2항에 있어서, 항체가 모노클로날 또는 키메릭 항체이거나 이의 항원-인지 단편인 결합체.
- 제 1 항 내지 3항중 어느 한 항에 있어서, Ar이 페닐, 일치환된 페닐 또는 피롤릴인 결합체.
- 제 1 항에 있어서, L/IC2와 4-데스아세틸-23-데스메톡시-빈블라스틴, 카보닐-4-벤질리덴하이드라지드의 결합체.
- 활성화제로서 제 1 항 내지 5항 중 어느 한 항에서 청구한 결합체를, 하나 이상의 약제학적으로 허용되는 담체 또는 희석제와 결합된 형태로 함유하는 약제학적 제제.
- 하기 일반식(A)의 화합물.상기식에서, R는 하이드록시, 산-활성화 그룹, 염을 완성시키는 부분, 또는 산-보호 그룹이고, X, Y, Ar 및 V는 제1항에서 정의한 바와 같다.
- 제 7 항에 있어서, Ar이 피롤릴 또는 p-페닐인 화합물.
- (A) 제 1 항에서 정의한 바와 같은 일반식(Ab)의 생리학적으로 허용되는 항체 또는 이의 항원-인지 단편을 일반식(A)의 중간물질과 반응시키거나, (B)일반식 (B)의 변형된 항체를 일반식(C)의 동량의 하이드라지드와 반응시킴을 특징으로 하여, 제 1 항 내지 5항중 어느 한 항에서 청구한 결합체를 제조하는 방법.H2N-NH-V (C)상기식에서, R5는 하이드록시, 산-활성화 그룹, 염을 완성시키는 부분 또는 산-보호 그룹이고, Ab, X, Y, Ar, Z, m 및 V는 제 1 항에서 정의한 바와 같다.
- 제 9 항의 방법으로 제조된 일반식(Ⅰ)의 결합체.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/230,084 US5006652A (en) | 1988-08-08 | 1988-08-08 | Intermediates for antibody-vinca drug conjugates |
US230,084 | 1988-08-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
KR900002804A true KR900002804A (ko) | 1990-03-23 |
Family
ID=22863896
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019890011217A KR900002804A (ko) | 1988-08-08 | 1989-08-07 | 세포독성 약물 결합체 및 이의 제조방법 |
Country Status (15)
Country | Link |
---|---|
US (1) | US5006652A (ko) |
EP (1) | EP0354728A3 (ko) |
JP (1) | JPH02131499A (ko) |
KR (1) | KR900002804A (ko) |
CN (1) | CN1040205A (ko) |
AR (1) | AR245368A1 (ko) |
AU (1) | AU619329B2 (ko) |
DK (1) | DK382989A (ko) |
HU (1) | HU206377B (ko) |
IL (1) | IL91182A0 (ko) |
MX (1) | MX164971B (ko) |
NZ (1) | NZ230200A (ko) |
PH (1) | PH27351A (ko) |
PT (1) | PT91372A (ko) |
ZA (1) | ZA895908B (ko) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5776093A (en) | 1985-07-05 | 1998-07-07 | Immunomedics, Inc. | Method for imaging and treating organs and tissues |
AU633867B2 (en) * | 1989-02-02 | 1993-02-11 | Eli Lilly And Company | Delivery of cytotoxic agents |
US5272253A (en) * | 1991-07-01 | 1993-12-21 | Eli Lilly And Company | Cluster conjugates of drugs with antibodies |
ES2049656B1 (es) * | 1992-10-08 | 1994-11-16 | Lilly Co Eli | Grupos de conjugados de farmacos con anticuerpos. |
GR1001459B (el) * | 1992-10-08 | 1993-12-30 | Lilly Co Eli | Σύμπλεγμα συζυγών φαρμάκων με αντισώματα. |
US5773001A (en) * | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US20030119724A1 (en) * | 1995-11-22 | 2003-06-26 | Ts`O Paul O.P. | Ligands to enhance cellular uptake of biomolecules |
AU2002217980A1 (en) | 2000-12-01 | 2002-06-11 | Cell Works Inc. | Conjugates of glycosylated/galactosylated peptide |
DE60231868D1 (de) | 2001-04-24 | 2009-05-20 | Purdue Research Foundation | Folat-mimetika und deren folatrezeptorbindende konjugate |
WO2003097647A1 (en) * | 2002-05-15 | 2003-11-27 | Endocyte, Inc. | Vitamin-mitomycin conjugates |
DK1592457T3 (da) | 2003-01-27 | 2012-10-22 | Endocyte Inc | Folat-vinblastin-konjugat som lægemiddel |
JP5149620B2 (ja) | 2004-07-23 | 2013-02-20 | エンドサイト,インコーポレイテッド | 2価リンカーおよびその結合体 |
US8044200B2 (en) * | 2005-03-16 | 2011-10-25 | Endocyte, Inc. | Synthesis and purification of pteroic acid and conjugates thereof |
AU2006279304A1 (en) * | 2005-08-19 | 2007-02-22 | Endocyte, Inc. | Multi-drug ligand conjugates |
EP2382995A3 (en) * | 2005-08-19 | 2013-09-25 | Endocyte, Inc. | Ligand conjugates of Vinca alkaloids, analogs and derivatives |
WO2008101231A2 (en) * | 2007-02-16 | 2008-08-21 | Endocyte, Inc. | Methods and compositions for treating and diagnosing kidney disease |
WO2008112873A2 (en) * | 2007-03-14 | 2008-09-18 | Endocyte, Inc. | Binding ligand linked drug delivery conjugates of tubulysins |
CN104383553A (zh) * | 2007-06-25 | 2015-03-04 | 恩多塞特公司 | 含有亲水性间隔区接头的共轭物 |
US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
EP2209374B1 (en) | 2007-10-25 | 2014-12-03 | Endocyte, Inc. | Tubulysins and processes for preparing |
US10080805B2 (en) | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
BR112015008365A2 (pt) | 2012-10-16 | 2017-07-04 | Endocyte Inc | composto da fórmula b-l(d)x, ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto, composição de forma de dosagem unitária ou dose unitária, composição para tratar um câncer em um paciente, e método para tratar um câncer em um paciente |
PT2968440T (pt) | 2013-03-15 | 2019-07-31 | Zymeworks Inc | Compostos citotóxicos e antimitóticos e métodos de utilização dos mesmos |
EP3086815B1 (en) | 2013-12-27 | 2022-02-09 | Zymeworks Inc. | Sulfonamide-containing linkage systems for drug conjugates |
EP3194421B1 (en) | 2014-09-17 | 2021-11-03 | Zymeworks Inc. | Cytotoxic and anti-mitotic compounds, and methods of using the same |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4203898A (en) * | 1977-08-29 | 1980-05-20 | Eli Lilly And Company | Amide derivatives of VLB, leurosidine, leurocristine and related dimeric alkaloids |
FI820020L (fi) * | 1981-01-12 | 1982-07-13 | Lilly Industries Ltd | Immunoglobulinkonjugater |
US4631190A (en) * | 1981-06-26 | 1986-12-23 | Shen Wei C | Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers |
CA1203164A (en) * | 1982-03-09 | 1986-04-15 | Thomas J. Mckearn | Antibody conjugates |
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 |
EP0124502B1 (fr) * | 1983-04-29 | 1991-06-12 | OMNICHEM Société anonyme | Nouveaux conjugués de la vinblastine et de ses dérivés, procédé pour leur préparation et compositions pharmaceutiques contenant ces conjugués |
LU86157A1 (fr) * | 1985-11-12 | 1987-06-26 | Omnichem Sa | Nouveau procede de fabrication de conjugues de la vinblastine et de ses derives |
US4675400A (en) * | 1985-06-17 | 1987-06-23 | Eli Lilly And Company | Bifunctional derivatives of 4-desacetyl indole-dihydroindole alkaloids |
EP0232693A3 (fr) * | 1985-12-16 | 1988-04-06 | La Region Wallonne | Conjugués de la vinblastine et de ses dérivés, procédé pour leur préparation et compositions pharmaceutiques les contenant |
GB8610551D0 (en) * | 1986-04-30 | 1986-06-04 | Hoffmann La Roche | Polypeptide & protein derivatives |
IL82579A0 (en) * | 1986-05-27 | 1987-11-30 | 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 |
FR2610198B1 (fr) * | 1987-02-03 | 1990-06-15 | Ire Celltarg Sa | Conjugues d'hydrazide d'alcaloide de vinca lie a une immunoglobuline, procede de preparation et compositions pharmaceutiques en comprenant |
IL89043A0 (en) * | 1988-01-27 | 1989-08-15 | Lilly Co Eli | Antibody conjugates |
-
1988
- 1988-08-08 US US07/230,084 patent/US5006652A/en not_active Expired - Fee Related
-
1989
- 1989-08-02 ZA ZA895908A patent/ZA895908B/xx unknown
- 1989-08-02 IL IL91182A patent/IL91182A0/xx unknown
- 1989-08-03 NZ NZ230200A patent/NZ230200A/xx unknown
- 1989-08-03 EP EP19890307915 patent/EP0354728A3/en not_active Ceased
- 1989-08-03 PT PT91372A patent/PT91372A/pt unknown
- 1989-08-04 AU AU39339/89A patent/AU619329B2/en not_active Ceased
- 1989-08-04 DK DK382989A patent/DK382989A/da not_active Application Discontinuation
- 1989-08-04 MX MX17079A patent/MX164971B/es unknown
- 1989-08-04 PH PH39050A patent/PH27351A/en unknown
- 1989-08-04 AR AR89314592A patent/AR245368A1/es active
- 1989-08-07 HU HU893992A patent/HU206377B/hu not_active IP Right Cessation
- 1989-08-07 CN CN89105544A patent/CN1040205A/zh active Pending
- 1989-08-07 JP JP1205545A patent/JPH02131499A/ja active Pending
- 1989-08-07 KR KR1019890011217A patent/KR900002804A/ko not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
HUT50488A (en) | 1990-02-28 |
EP0354728A2 (en) | 1990-02-14 |
AR245368A1 (es) | 1994-01-31 |
DK382989A (da) | 1990-02-09 |
AU619329B2 (en) | 1992-01-23 |
IL91182A0 (en) | 1990-03-19 |
EP0354728A3 (en) | 1991-04-10 |
ZA895908B (en) | 1991-04-24 |
AU3933989A (en) | 1990-02-08 |
MX164971B (es) | 1992-10-09 |
PT91372A (pt) | 1990-03-08 |
JPH02131499A (ja) | 1990-05-21 |
US5006652A (en) | 1991-04-09 |
NZ230200A (en) | 1991-11-26 |
DK382989D0 (da) | 1989-08-04 |
CN1040205A (zh) | 1990-03-07 |
PH27351A (en) | 1993-06-21 |
HU206377B (en) | 1992-10-28 |
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WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |