WO2004005470A2 - Antibodies to non-shed muc1 and muc16, and uses thereof - Google Patents

Antibodies to non-shed muc1 and muc16, and uses thereof Download PDF

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Publication number
WO2004005470A2
WO2004005470A2 PCT/US2003/020907 US0320907W WO2004005470A2 WO 2004005470 A2 WO2004005470 A2 WO 2004005470A2 US 0320907 W US0320907 W US 0320907W WO 2004005470 A2 WO2004005470 A2 WO 2004005470A2
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WO
WIPO (PCT)
Prior art keywords
antibody
muclό
mucl
shed
antigen
Prior art date
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Ceased
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PCT/US2003/020907
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English (en)
French (fr)
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WO2004005470A3 (en
Inventor
Gillian Payne
Thomas Chittenden
Viktor Goldmakher
Philip Chun
Kristin Sneider-Mulready
Carol A. Vater
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Immunogen Inc
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Immunogen Inc
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Filing date
Publication date
Application filed by Immunogen Inc filed Critical Immunogen Inc
Priority to CA002491017A priority Critical patent/CA2491017A1/en
Priority to EP03763146A priority patent/EP1536814A4/en
Priority to JP2004519814A priority patent/JP2006502110A/ja
Priority to AU2003247762A priority patent/AU2003247762B2/en
Publication of WO2004005470A2 publication Critical patent/WO2004005470A2/en
Publication of WO2004005470A3 publication Critical patent/WO2004005470A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/575Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57515Immunoassay; Biospecific binding assay; Materials therefor for cancer of the breast
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • A61K47/6869Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3076Immunoglobulins [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 against structure-related tumour-associated moieties
    • C07K16/3092Immunoglobulins [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 against structure-related tumour-associated moieties against tumour-associated mucins
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/575Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57545Immunoassay; Biospecific binding assay; Materials therefor for cancer of the ovaries
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77Internalization into the cell
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701Details
    • G01N2333/4725Mucins, e.g. human intestinal mucin

Definitions

  • TEPs tumor-activated prodrugs
  • the term "monoclonal antibody” as used herein refers to a substantially homogeneous population of antibodies, i.e., the individual antibodies comprising the population are identical in specificity and affinity except for possible naturally occurring mutations that may be present in minor amounts. Note that a monoclonal antibody composition may contain more than one monoclonal antibody. Thus, the modifier “monoclonal” indicates the character of the antibody as a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
  • a "non-shed extracellular portion" of an antigen, such as Mucl or Mucl ⁇ is herein defined as an extracellular portion of the antigen that is substantially not released into the extracellular medium or blood.
  • the juxtamembrane regions of shed antigens can be determined experimentally by routine methods.
  • the cleavage site of shed type I and type II membrane protein antigens can be identified using recombinant, epitope-tagged cDNAs of the antigen in question in a modification of the procedure used by Parry et al. to identify the Mucl endoplasmic reticulum processing cleavage sites (Parry, S., Silverman, H. S., McDermott, K., Willis, A., Hollingsworth, M. A., and Harris, A. (2001) Identification of MUC 1 proteolytic cleavage sites in vivo. Biochem Biophys Res Commun 283, 715-20).
  • mammals can be immunized with cells stably expressing recombinant shed antigen, or portions thereof, such as portions consisting only of the non-shed domain.
  • Suitable vectors for expression in mammalian cells include well-known derivatives of S V-40, adenovirus, retrovirus-derived DNA sequences and shuttle vectors derived from combinations of functional mammalian vectors, functional plasmids and phage DNA.
  • Taxanes are also preferred cytotoxic agents. Taxanes suitable for use in the present invention are disclosed in U.S. Patent Nos. 6,372,738 and 6,340,701.
  • Suitable carriers, diluents and/or excipients include: (1) Dulbecco's phosphate buffered saline, pH about 7.4, containing about 1 mg/ml to 25 mg/ml human serum albumin, (2) 0.9% saline (0.9% w/v NaCl), and (3) 5% (w/v) dextrose.
  • the method of the present invention can be practiced in vitro, in vivo, or ex vivo.
  • the method of the present invention may be used for screening and/or treatment a cancer in which Muc 1 or Muc 16 expression is elevated.
  • a Mucl ⁇ antibody, Ml 1 (gift from Dr. Timothy O'Brien; University of Arkansas) recognizing the shed domain was used as a control antibody for the flow cytometry screen.
  • the histograms of 24 representative clones from the Mucl ⁇ hybridoma screening are shown in Figure 5 A. The histograms generally fall into three categories: histograms in which a subpopulation of cells exhibit a shift in fluorescence, histograms in which the entire population of cells exhibits a fluorescence shift, and histograms in which two populations of cells show fluorescence shifts of different magnitudes.
  • FlagMuc 1 Xb aR ggaatctagacttgtcatcgtcgtccttgtagtcggtagagcttgcatgaccagaa
  • the epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin. J Biol Chem 276, 35239-42.
  • CA 125 gene an extracellular superstructure dominated by repeat sequences. Tumour Biol 22, 348-66.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Reproductive Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US2003/020907 2002-07-03 2003-07-03 Antibodies to non-shed muc1 and muc16, and uses thereof Ceased WO2004005470A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002491017A CA2491017A1 (en) 2002-07-03 2003-07-03 Antibodies to non-shed muc1 and muc16, and uses thereof
EP03763146A EP1536814A4 (en) 2002-07-03 2003-07-03 ANTIQUE RPER AGAINST NON-SHED-MUC1 AND MUC16, AND ITS USES
JP2004519814A JP2006502110A (ja) 2002-07-03 2003-07-03 非放出Muc1およびMuc16に対する抗体、およびその使用
AU2003247762A AU2003247762B2 (en) 2002-07-03 2003-07-03 Antibodies to non-shed MUC1 and MUC16, and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39309402P 2002-07-03 2002-07-03
US60/393,094 2002-07-03

Publications (2)

Publication Number Publication Date
WO2004005470A2 true WO2004005470A2 (en) 2004-01-15
WO2004005470A3 WO2004005470A3 (en) 2004-04-29

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PCT/US2003/020907 Ceased WO2004005470A2 (en) 2002-07-03 2003-07-03 Antibodies to non-shed muc1 and muc16, and uses thereof

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US (1) US7202346B2 (https=)
EP (1) EP1536814A4 (https=)
JP (1) JP2006502110A (https=)
AU (1) AU2003247762B2 (https=)
CA (1) CA2491017A1 (https=)
WO (1) WO2004005470A2 (https=)

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WO2005019269A3 (en) * 2002-11-27 2005-05-12 Minerva Biotechnologies Corp Techniques and compositions for the diagnosis and treatment of cancer (muc1)
EP1551876A4 (en) * 2002-10-16 2005-12-14 Euro Celtique Sa ANTIBODIES BINDING TO CELL ASSOCIATED CA 125 / 0722P, AND METHOD FOR THEIR USE
WO2005117986A3 (en) * 2004-06-01 2006-06-15 Genentech Inc Antibody drug conjugates and methods
WO2006081553A2 (en) 2005-01-28 2006-08-03 Ramot At Tel Aviv University, Ltd. ANTI-MUC1 α/ß ANTIBODIES
WO2007001851A3 (en) * 2005-06-20 2007-03-22 Genentech Inc Compositions and methods for the diagnosis and treatment of tumor
US7700715B2 (en) 2000-11-27 2010-04-20 Minerva Biotechnologies Corporation Diagnostic tumor markers, drug screening for tumorigenesis inhibition, and compositions and methods for treatment of cancer
EP1981527A4 (en) * 2006-01-27 2011-05-04 Univ Mississippi Medical Ct THERMAL TARGETED RELEASE OF MEDICAMENTS, U.A. DOXORUBICIN
US7989598B2 (en) 2003-10-10 2011-08-02 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates and methods of making said conjugates
WO2015116753A1 (en) * 2014-01-29 2015-08-06 Dana-Farber Cancer Institute, Inc. Antibodies against the muc1-c/extracellular domain (muc1-c/ecd)
US9169328B2 (en) 2010-03-26 2015-10-27 Memorial Sloan Kettering Cancer Center Antibodies to MUC16 and methods of use thereof
CN105950647A (zh) * 2016-05-16 2016-09-21 浙江理工大学 一种高效表达与制备外分泌型人源ca125的方法
USRE47194E1 (en) 2007-05-08 2019-01-08 Genentech, Inc. Cysteine engineered anti-MUC16 antibodies and antibody drug conjugates
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US10617773B2 (en) 2016-08-05 2020-04-14 Dana-Farber Cancer Institute, Inc. Antibodies against the MUC1-C/extracellular domain (MUC1-C/ECD)
US10640508B2 (en) 2017-10-13 2020-05-05 Massachusetts Institute Of Technology Diazene directed modular synthesis of compounds with quaternary carbon centers
US10918627B2 (en) 2016-05-11 2021-02-16 Massachusetts Institute Of Technology Convergent and enantioselective total synthesis of Communesin analogs
US10918735B2 (en) 2012-12-04 2021-02-16 Massachusetts Institute Of Technology Substituted pyrazino[1′,2′:1,5]pyrrolo[2,3-b]indole-1,4-diones for cancer treatment
US11066480B2 (en) 2015-03-17 2021-07-20 Memorial Sloan Kettering Cancer Center Anti-MUC16 antibodies and uses thereof
US11746159B2 (en) 2015-02-10 2023-09-05 Minerva Biotechnologies Corporation Humanized anti-MUC1* antibodies

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US7498298B2 (en) 2003-11-06 2009-03-03 Seattle Genetics, Inc. Monomethylvaline compounds capable of conjugation to ligands
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