SK15582003A3 - Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents
Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie Download PDFInfo
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- SK15582003A3 SK15582003A3 SK1558-2003A SK15582003A SK15582003A3 SK 15582003 A3 SK15582003 A3 SK 15582003A3 SK 15582003 A SK15582003 A SK 15582003A SK 15582003 A3 SK15582003 A3 SK 15582003A3
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- antibody
- cytotoxic
- antibody molecule
- adenocarcinoma
- maytansinoid
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Classifications
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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
- A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
-
- 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
-
- 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
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01112227A EP1258255A1 (en) | 2001-05-18 | 2001-05-18 | Conjugates of an antibody to CD44 and a maytansinoid |
PCT/EP2002/005413 WO2002094325A2 (en) | 2001-05-18 | 2002-05-16 | Cytotoxic cd44 antibody immunoconjugates |
Publications (1)
Publication Number | Publication Date |
---|---|
SK15582003A3 true SK15582003A3 (sk) | 2004-04-06 |
Family
ID=8177473
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1558-2003A SK15582003A3 (sk) | 2001-05-18 | 2002-05-16 | Cytotoxické CD44 protilátkové imunokonjugáty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie |
Country Status (24)
Country | Link |
---|---|
EP (2) | EP1258255A1 (es) |
JP (1) | JP2004529963A (es) |
KR (1) | KR20030097883A (es) |
CN (1) | CN1509187A (es) |
AR (1) | AR035977A1 (es) |
BG (1) | BG108366A (es) |
BR (1) | BR0209862A (es) |
CA (1) | CA2443438A1 (es) |
CO (1) | CO5550468A2 (es) |
CZ (1) | CZ20033477A3 (es) |
EA (1) | EA200301159A1 (es) |
EE (1) | EE200300568A (es) |
HR (1) | HRP20030932A2 (es) |
HU (1) | HUP0400046A3 (es) |
IL (1) | IL157965A0 (es) |
MX (1) | MXPA03010432A (es) |
NO (1) | NO20035108L (es) |
NZ (1) | NZ530167A (es) |
PE (1) | PE20021097A1 (es) |
PL (1) | PL365480A1 (es) |
SK (1) | SK15582003A3 (es) |
WO (1) | WO2002094325A2 (es) |
YU (1) | YU91503A (es) |
ZA (1) | ZA200307364B (es) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8071072B2 (en) * | 1999-10-08 | 2011-12-06 | Hoffmann-La Roche Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
US6441163B1 (en) * | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
EP1417974A1 (en) * | 2002-11-08 | 2004-05-12 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and radiotherapy |
DE10256083A1 (de) * | 2002-11-29 | 2004-08-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Expressionsvektor, Verfahren zur Herstellung von heterologen Genprodukten und Selektionsverfahren für hochproduzierende rekombinante Zellen |
US7384744B2 (en) | 2002-11-29 | 2008-06-10 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | Expression vector, methods for the production of heterologous gene products and for the selection of recombinant cells producing high levels of such products |
BRPI0410748B8 (pt) * | 2003-05-20 | 2021-05-25 | Immunogen Inc | compostos de maitansinóides, suas composições farmacêuticas, métodos de esterificação de maitansinóides, bem como métodos para a sua produção, e conjugado de maitansinóide-agente de ligação celular |
US7276497B2 (en) | 2003-05-20 | 2007-10-02 | Immunogen Inc. | Cytotoxic agents comprising new maytansinoids |
CN1922199B (zh) * | 2003-07-21 | 2013-10-30 | 伊缪诺金公司 | Ca6抗原特异性细胞毒性偶联物及其应用方法 |
EP2316857A1 (en) * | 2004-02-12 | 2011-05-04 | Morphotek, Inc. | Monoclonal antibodies that specifically bind to folate receptor alpha |
WO2006062779A2 (en) | 2004-12-09 | 2006-06-15 | Centocor, Inc. | Anti-integrin immunoconjugates, methods and uses |
AU2006213662B2 (en) * | 2005-02-11 | 2010-08-05 | Immunogen, Inc. | Process for preparing stable drug conjugates |
ES2386367T3 (es) | 2005-03-10 | 2012-08-17 | Morphotek, Inc. | Anticuerpos anti-mesotelina |
ZA200708694B (en) * | 2005-04-15 | 2009-01-28 | Immunogen Inc | Elimination of heterogeneous or mixed cell population in tumors |
CA2607444C (en) | 2005-04-22 | 2015-03-10 | Morphotek, Inc. | Antibodies with immune effector activity and that internalize in folate receptor alpha-positive cells |
PL1928503T3 (pl) | 2005-08-24 | 2012-12-31 | Immunogen Inc | Sposób wytwarzania koniugatów majtazynoid-przeciwciało |
EP1806365A1 (en) | 2006-01-05 | 2007-07-11 | Boehringer Ingelheim International GmbH | Antibody molecules specific for fibroblast activation protein and immunoconjugates containing them |
AR059900A1 (es) * | 2006-03-17 | 2008-05-07 | Genentech Inc | Anticuerpos anti-tat226 e inmunoconjugados |
CN104984360A (zh) | 2009-06-03 | 2015-10-21 | 伊缪诺金公司 | 轭合方法 |
AR078471A1 (es) * | 2009-10-02 | 2011-11-09 | Sanofi Aventis | COMPUESTOS MAITANSINOIDES Y EL USO DE ESTOS PARA PREPARAR CONJUGADOS CON UN ANTICUERPO LOS CUALES SE UTILIZAN COMO AGENTES ANTICANCERIGENOS Y EL PROCEDIMIENTO DE PREPARACIoN DE ESTOS CONJUGADOS |
PT2691155T (pt) | 2011-03-29 | 2019-02-19 | Immunogen Inc | Preparação de conjugados de anticorpo de maitansinoide por processo de uma etapa |
CN102337298B (zh) * | 2011-08-19 | 2013-11-06 | 黄开红 | 一种输送siRNA的免疫纳米载体及其制备方法和应用 |
AU2013326881B2 (en) | 2012-10-04 | 2018-08-02 | Immunogen, Inc. | Use of a PVDF membrane to purify cell-binding agent cytotoxic agent conjugates |
GB201220889D0 (en) | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived peptides for treating metastasizing cancers |
GB201220899D0 (en) * | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived pegylated peptides |
GB201220891D0 (en) * | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived peptides for treating breast cancers |
GB201220901D0 (en) * | 2012-11-21 | 2013-01-02 | Kit Karlsrusher Inst Fuer Technologie Und Inst Fuer Toxikologie Und Genetik And Amcure Gmbh | CD44v6-derived peptides for treating pancreatic cancer |
EA038192B1 (ru) | 2013-08-26 | 2021-07-21 | Регенерон Фармасьютикалз, Инк. | Фармацевтические композиции, содержащие диастереомеры макролида, способы их синтезирования и терапевтическое применение |
GB201421647D0 (en) | 2014-12-05 | 2015-01-21 | Amcure Gmbh And Ruprecht-Karls-Universitat And Karlsruher Institut F�R Technologie | CD44v6-derived cyclic peptides for treating cancers and angiogenesis related diseases |
WO2016150521A1 (en) * | 2015-03-26 | 2016-09-29 | Fundación Imdea Nanociencia | Functionalised magnetic nanoparticle |
KR20210004961A (ko) * | 2018-02-22 | 2021-01-13 | 아브마트 상하이 컴퍼니, 엘티디. | 치료 항체 및 그의 용도 |
CN114057874B (zh) * | 2020-07-31 | 2023-05-05 | 北京市神经外科研究所 | 抗cd44的单链抗体及其在制备治疗肿瘤的药物中的用途 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2026147C (en) * | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5208020A (en) * | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
UY24389A1 (es) * | 1995-12-06 | 2001-10-25 | Karlsruhe Forschzent | Composición farmacéutica para el tratamiento de carcinoma de epitelio plano |
DE19648209A1 (de) * | 1996-11-21 | 1998-05-28 | Boehringer Ingelheim Int | Verfahren zur Tumorzelldepletion CD34-positiver Zellen |
DE19708713C2 (de) * | 1997-03-04 | 2002-11-28 | Boehringer Ingelheim Int | Verwendung von anti-CD44 Antikörpern enthaltenden Präparationen zur Behandlung bestimmter Tumore und zur Unterdrückung von Immunreaktionen |
IL147241A0 (en) * | 1999-06-25 | 2002-08-14 | Genentech Inc | METHODS OF TREATMENT USING ANTI ErbB ANTIBODY-MAYTANSINOID CONJUGATES |
EP1229934B1 (en) * | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
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2001
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2002
- 2002-05-16 HU HU0400046A patent/HUP0400046A3/hu unknown
- 2002-05-16 EA EA200301159A patent/EA200301159A1/ru unknown
- 2002-05-16 WO PCT/EP2002/005413 patent/WO2002094325A2/en not_active Application Discontinuation
- 2002-05-16 JP JP2002591041A patent/JP2004529963A/ja active Pending
- 2002-05-16 BR BR0209862-8A patent/BR0209862A/pt not_active IP Right Cessation
- 2002-05-16 CA CA002443438A patent/CA2443438A1/en not_active Abandoned
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- 2002-05-16 PL PL02365480A patent/PL365480A1/xx not_active Application Discontinuation
- 2002-05-16 YU YU91503A patent/YU91503A/sh unknown
- 2002-05-16 CN CNA028101634A patent/CN1509187A/zh active Pending
- 2002-05-16 EP EP02753054A patent/EP1395290A2/en not_active Withdrawn
- 2002-05-16 EE EEP200300568A patent/EE200300568A/xx unknown
- 2002-05-16 CZ CZ20033477A patent/CZ20033477A3/cs unknown
- 2002-05-16 SK SK1558-2003A patent/SK15582003A3/sk not_active Application Discontinuation
- 2002-05-16 IL IL15796502A patent/IL157965A0/xx unknown
- 2002-05-16 KR KR10-2003-7015037A patent/KR20030097883A/ko not_active Application Discontinuation
- 2002-05-16 NZ NZ530167A patent/NZ530167A/en unknown
- 2002-05-17 AR ARP020101829A patent/AR035977A1/es not_active Application Discontinuation
- 2002-05-17 PE PE2002000420A patent/PE20021097A1/es not_active Application Discontinuation
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2003
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- 2003-11-17 BG BG108366A patent/BG108366A/bg unknown
- 2003-11-17 NO NO20035108A patent/NO20035108L/no not_active Application Discontinuation
- 2003-11-18 CO CO03101695A patent/CO5550468A2/es not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
EP1258255A1 (en) | 2002-11-20 |
PE20021097A1 (es) | 2003-02-13 |
BG108366A (bg) | 2004-09-30 |
WO2002094325A3 (en) | 2003-04-17 |
CZ20033477A3 (en) | 2004-05-12 |
HUP0400046A3 (en) | 2006-02-28 |
KR20030097883A (ko) | 2003-12-31 |
BR0209862A (pt) | 2004-06-08 |
NZ530167A (en) | 2005-10-28 |
EP1395290A2 (en) | 2004-03-10 |
CO5550468A2 (es) | 2005-08-31 |
YU91503A (sh) | 2006-05-25 |
AR035977A1 (es) | 2004-07-28 |
NO20035108D0 (no) | 2003-11-17 |
CA2443438A1 (en) | 2002-11-28 |
CN1509187A (zh) | 2004-06-30 |
EE200300568A (et) | 2004-04-15 |
EA200301159A1 (ru) | 2004-06-24 |
PL365480A1 (en) | 2005-01-10 |
NO20035108L (no) | 2003-11-17 |
HRP20030932A2 (en) | 2004-04-30 |
JP2004529963A (ja) | 2004-09-30 |
IL157965A0 (en) | 2004-03-28 |
ZA200307364B (en) | 2004-04-20 |
WO2002094325A2 (en) | 2002-11-28 |
MXPA03010432A (es) | 2004-04-02 |
HUP0400046A2 (hu) | 2004-04-28 |
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