WO2002049672A3 - Conjugates of antibodies and anticancer drugs - Google Patents

Conjugates of antibodies and anticancer drugs Download PDF

Info

Publication number
WO2002049672A3
WO2002049672A3 PCT/CA2001/001854 CA0101854W WO0249672A3 WO 2002049672 A3 WO2002049672 A3 WO 2002049672A3 CA 0101854 W CA0101854 W CA 0101854W WO 0249672 A3 WO0249672 A3 WO 0249672A3
Authority
WO
WIPO (PCT)
Prior art keywords
conjugates
antibodies
anticancer drugs
compound
target cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CA2001/001854
Other languages
French (fr)
Other versions
WO2002049672A2 (en
Inventor
H Uri Saragovi
Veronique Guillemard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
McGill University
Original Assignee
McGill University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by McGill University filed Critical McGill University
Priority to EP01271229A priority Critical patent/EP1343531A2/en
Priority to AU2002216864A priority patent/AU2002216864A1/en
Publication of WO2002049672A2 publication Critical patent/WO2002049672A2/en
Publication of WO2002049672A3 publication Critical patent/WO2002049672A3/en
Priority to US10/600,623 priority patent/US20040115209A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • 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
    • A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
    • 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
    • A61K47/6847—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 hormone or a hormone-releasing or -inhibiting factor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Endocrinology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention relates to a compound to selectively kill or protect a target cell in a patient with reduced systemic toxicity, which comprises a compound of the formula: W-Z-X wherein, X is a toxic agent or protective agent; W is a biologically active molecule which is adapted to selectively bind the target cell directly or indirectly; and Z is a breakable linker which covalently links W and X together, wherein the linked W remains bioavailable and bioactive, whereby the breakable linker releases the toxic agent or protective agent into the cell.
PCT/CA2001/001854 2000-12-21 2001-12-21 Conjugates of antibodies and anticancer drugs Ceased WO2002049672A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP01271229A EP1343531A2 (en) 2000-12-21 2001-12-21 Conjugates of antibodies and anticancer drugs
AU2002216864A AU2002216864A1 (en) 2000-12-21 2001-12-21 Conjugates of antibodies and anticancer drugs
US10/600,623 US20040115209A1 (en) 2000-12-21 2003-06-20 Compound targeted for specific cells with reduced systemic toxicity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US25698700P 2000-12-21 2000-12-21
US60/256,987 2000-12-21

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/600,623 Continuation US20040115209A1 (en) 2000-12-21 2003-06-20 Compound targeted for specific cells with reduced systemic toxicity

Publications (2)

Publication Number Publication Date
WO2002049672A2 WO2002049672A2 (en) 2002-06-27
WO2002049672A3 true WO2002049672A3 (en) 2003-01-03

Family

ID=22974423

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2001/001854 Ceased WO2002049672A2 (en) 2000-12-21 2001-12-21 Conjugates of antibodies and anticancer drugs

Country Status (4)

Country Link
US (1) US20040115209A1 (en)
EP (1) EP1343531A2 (en)
AU (1) AU2002216864A1 (en)
WO (1) WO2002049672A2 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110034381A1 (en) * 2002-01-22 2011-02-10 David Kleinberg Methods for Therapeutic Treatment of Benign Prostatic Hypertrophy (BPH)
EP1680073B1 (en) * 2003-10-21 2013-01-02 IGF Oncology, LLC Compounds and method for treating cancer
US9011880B2 (en) 2003-10-21 2015-04-21 Igf Oncology, Llc Compounds and methods for treating cancer
CA2616906A1 (en) * 2005-05-12 2006-11-23 Tapestry Pharmaceuticals, Inc. Molecular constructs suitable for targeted conjugates
EP2281004A4 (en) * 2008-04-14 2012-02-15 Proscan Rx Pharma Inc Prostate specific membrane antigen antibodies and antigen binding fragments
FR2959994B1 (en) 2010-05-12 2012-08-24 Lfb Biotechnologies NOVEL 12G4 MUTUS HUMANIZED ANTIBODIES AND THEIR FRAGMENTS DIRECTED AGAINST THE HUMAN TYPE II ANTI-MULLERIAN HORMONE RECEPTOR
CA2936675C (en) 2014-01-12 2023-06-27 Igf Oncology, Llc Fusion proteins containing insulin-like growth factor-1 and epidermal growth factor and variants thereof and uses thereof
CN117442747A (en) 2017-05-21 2024-01-26 Igf肿瘤公司 Insulin-like growth factors—chemotherapeutic conjugates for the treatment of myelodysplastic syndromes

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3808166A1 (en) * 1987-03-11 1988-09-22 Erba Carlo Spa IMMUNGLOBULIN CONJUGATES, METHOD FOR THE PRODUCTION AND USE THEREOF AND PHARMACEUTICAL AGENTS CONTAINING THEM
WO1988009823A1 (en) * 1987-06-05 1988-12-15 Cytogen Corporation Amine derivatives of anthracycline antibiotics and antibody conjugates thereof
EP0328147A2 (en) * 1988-02-11 1989-08-16 Bristol-Myers Squibb Company Anthracycline immunoconjugates having a novel linker and methods for their production
EP0398305A2 (en) * 1989-05-17 1990-11-22 Bristol-Myers Squibb Company Anthracycline conjugates having a novel linker and methods for their production
EP0476408A1 (en) * 1990-09-17 1992-03-25 Research Corporation Technologies, Inc. Chemical conjugation of morpholino anthracyclines to antibodies
WO1996006116A1 (en) * 1994-08-19 1996-02-29 Regents Of The University Of Minnesota Immunoconjugates comprising tyrosine kinase inhibitors
US5833983A (en) * 1987-06-29 1998-11-10 The United States Of America As Represented By The Secretary Of Dept. Of Health And Human Services Interleukin 2 receptor and applications thereof
US5869045A (en) * 1989-06-30 1999-02-09 Bristol-Myers Squibb Company Antibody conjugates reactive with human carcinomas
WO2001038318A1 (en) * 1999-11-24 2001-05-31 Immunogen, Inc. Cytotoxic agents comprising taxanes and their therapeutic use

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5084560A (en) * 1986-06-30 1992-01-28 Oncogen Immunoconjugates and methods for their use in tumor therapy
US4997913A (en) * 1986-06-30 1991-03-05 Oncogen pH-sensitive immunoconjugates and methods for their use in tumor therapy
US5208323A (en) * 1989-08-10 1993-05-04 Universite Laval Coupling of an anti-tumor to an antibody using glutaraldehyde preactivated anti-tumor agent
US5258453A (en) * 1992-01-21 1993-11-02 University Of Utah Drug delivery system for the simultaneous delivery of drugs activatable by enzymes and light
GB9323429D0 (en) * 1993-11-12 1994-01-05 Wellcome Found Therapy
DE4433890C2 (en) * 1994-09-22 1999-02-18 Deutsches Krebsforsch Conjugate of an active ingredient and a native protein that is not considered foreign to the body
GB9525180D0 (en) * 1995-12-08 1996-02-07 Univ Mcgill Design of hormone-like antibodies with agonistic and antagonistic fuctions
US6030997A (en) * 1998-01-21 2000-02-29 Eilat; Eran Acid labile prodrugs
US6652864B1 (en) * 1998-12-21 2003-11-25 Asilomar Pharmaceuticals, Inc. Compounds for intracellular delivery of therapeutic moieties to nerve cells

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3808166A1 (en) * 1987-03-11 1988-09-22 Erba Carlo Spa IMMUNGLOBULIN CONJUGATES, METHOD FOR THE PRODUCTION AND USE THEREOF AND PHARMACEUTICAL AGENTS CONTAINING THEM
WO1988009823A1 (en) * 1987-06-05 1988-12-15 Cytogen Corporation Amine derivatives of anthracycline antibiotics and antibody conjugates thereof
US5833983A (en) * 1987-06-29 1998-11-10 The United States Of America As Represented By The Secretary Of Dept. Of Health And Human Services Interleukin 2 receptor and applications thereof
EP0328147A2 (en) * 1988-02-11 1989-08-16 Bristol-Myers Squibb Company Anthracycline immunoconjugates having a novel linker and methods for their production
EP0398305A2 (en) * 1989-05-17 1990-11-22 Bristol-Myers Squibb Company Anthracycline conjugates having a novel linker and methods for their production
US5869045A (en) * 1989-06-30 1999-02-09 Bristol-Myers Squibb Company Antibody conjugates reactive with human carcinomas
US6020145A (en) * 1989-06-30 2000-02-01 Bristol-Myers Squibb Company Methods for determining the presence of carcinoma using the antigen binding region of monoclonal antibody BR96
EP0476408A1 (en) * 1990-09-17 1992-03-25 Research Corporation Technologies, Inc. Chemical conjugation of morpholino anthracyclines to antibodies
WO1996006116A1 (en) * 1994-08-19 1996-02-29 Regents Of The University Of Minnesota Immunoconjugates comprising tyrosine kinase inhibitors
WO2001038318A1 (en) * 1999-11-24 2001-05-31 Immunogen, Inc. Cytotoxic agents comprising taxanes and their therapeutic use

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DUBOWCHIK G M ET AL: "Cathepsin B-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (Taxol), mitomycin C and doxorubicin.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. ENGLAND 1 DEC 1998, vol. 8, no. 23, 1 December 1998 (1998-12-01), pages 3347 - 3352, XP004143756, ISSN: 0960-894X *
GUILLEMARD V ET AL: "Taxane-antibody conjugates afford potent cytotoxicity, enhanced solubility, and tumor target selectivity.", CANCER RESEARCH, vol. 61, no. 2, 15 January 2001 (2001-01-15), pages 694 - 699, XP002203756, ISSN: 0008-5472 *
TRAIL P A ET AL: "Enhanced antitumor activity of paclitaxel in combination with the anticarcinoma immunoconjugate BR96-doxorubicin.", CLINICAL CANCER RESEARCH: AN OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH. UNITED STATES NOV 1999, vol. 5, no. 11, November 1999 (1999-11-01), pages 3632 - 3638, XP002203755, ISSN: 1078-0432 *

Also Published As

Publication number Publication date
EP1343531A2 (en) 2003-09-17
WO2002049672A2 (en) 2002-06-27
AU2002216864A1 (en) 2002-07-01
US20040115209A1 (en) 2004-06-17

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