WO2001062931A3 - ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF - Google Patents

ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF Download PDF

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Publication number
WO2001062931A3
WO2001062931A3 PCT/US2001/005923 US0105923W WO0162931A3 WO 2001062931 A3 WO2001062931 A3 WO 2001062931A3 US 0105923 W US0105923 W US 0105923W WO 0162931 A3 WO0162931 A3 WO 0162931A3
Authority
WO
WIPO (PCT)
Prior art keywords
egfrviii
antibodies
yield
antibody
methods
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/US2001/005923
Other languages
French (fr)
Other versions
WO2001062931A2 (en
Inventor
Ira Pastan
Richard Beers
Partha S Chowdhury
Darell Bigner
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.)
Duke University
US Department of Health and Human Services
Original Assignee
Duke University
US Department of Health and Human Services
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
Priority to BR0108646-4A priority Critical patent/BR0108646A/en
Priority to MXPA02008178A priority patent/MXPA02008178A/en
Priority to CA2400868A priority patent/CA2400868C/en
Priority to SK1223-2002A priority patent/SK12232002A3/en
Priority to DE60137202T priority patent/DE60137202D1/en
Priority to AU2001239857A priority patent/AU2001239857B9/en
Priority to EP01914471A priority patent/EP1266009B1/en
Priority to AU3985701A priority patent/AU3985701A/en
Priority to UA2002086976A priority patent/UA77157C2/en
Priority to NZ520622A priority patent/NZ520622A/en
Priority to US10/203,675 priority patent/US7129332B2/en
Priority to JP2001562705A priority patent/JP2003523771A/en
Application filed by Duke University, US Department of Health and Human Services filed Critical Duke University
Priority to HU0204142A priority patent/HUP0204142A3/en
Publication of WO2001062931A2 publication Critical patent/WO2001062931A2/en
Publication of WO2001062931A3 publication Critical patent/WO2001062931A3/en
Priority to BG106998A priority patent/BG106998A/en
Priority to NO20024034A priority patent/NO20024034L/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • A61K47/6849—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The invention provides antibodies for a mutant form of the epidermal growth factor receptor known as EGFRvIII. This mutant is found only or primarily on the surface of glioblastoma cells, and on cells of breast, ovarian and non-small cell lung carcinomas. The antibodies provided by the invention have higher affinity for EGFRvIII, and form immunotoxins with higher cytotoxicity and yield, than prior art antibodies, including the scFv designated MR1. In particular, the invention provides an antibody, designated MR1-1, which mutates MR1 in the CDR3 of the VH and VL chains to provide an antibody with especially good cytotoxicity. The invention provides additional antibodies in which MR1 is mutated in the CDR1 and 2 of VH or VL, or both, with better binding to EGFRvIII than that of the parental MR1 antibody.
PCT/US2001/005923 2000-02-25 2001-02-23 ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF Ceased WO2001062931A2 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
MXPA02008178A MXPA02008178A (en) 2000-02-25 2001-02-23 ANTI EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF.
CA2400868A CA2400868C (en) 2000-02-25 2001-02-23 Anti-egfrviii scfvs with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
SK1223-2002A SK12232002A3 (en) 2000-02-25 2001-02-23 Anti-EGFRvIII scFv with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
DE60137202T DE60137202D1 (en) 2000-02-25 2001-02-23 SCFV MOLECULES AGAINST EGFRVIII WITH IMPROVED CYTOTOXICITY AND YIELD, BASED IMMUNOXINE, AND METHOD OF USE THEREOF
AU2001239857A AU2001239857B9 (en) 2000-02-25 2001-02-23 Anti-EGFRvIII SCFVS with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
EP01914471A EP1266009B1 (en) 2000-02-25 2001-02-23 ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF
AU3985701A AU3985701A (en) 2000-02-25 2001-02-23 Anti-EGFRviii SCFVS with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
NZ520622A NZ520622A (en) 2000-02-25 2001-02-23 Anti-EGFRvIII scFvs with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
UA2002086976A UA77157C2 (en) 2000-02-25 2001-02-23 Polypeptide anti-egfrviii scfvs with improved cytotoxicity and output, molecule of nucleic acid, that codes the indicated polypeptide, and method of cell destructure with using of this polypeptide
BR0108646-4A BR0108646A (en) 2000-02-25 2001-02-23 Polypeptide, nucleic acid molecule, and, method for killing a cell carrying an antigen
JP2001562705A JP2003523771A (en) 2000-02-25 2001-02-23 Anti-EGFRvIII scFv with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
US10/203,675 US7129332B2 (en) 2000-02-25 2001-02-23 Anti-EGFRvIII scFvs with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
HU0204142A HUP0204142A3 (en) 2000-02-25 2001-02-23 Anti-egfrviii scfv-antibodies with improved cytotoxicity and yield, immunotoxins based thereon, and methods of use thereof
BG106998A BG106998A (en) 2000-02-25 2002-08-14 ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF
NO20024034A NO20024034L (en) 2000-02-25 2002-08-23 Anti-EGFRvIII SCFVS with improved cytotoxicity and yield, immunotoxins based thereon, and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US18503900P 2000-02-25 2000-02-25
US60/185,039 2000-02-25

Publications (2)

Publication Number Publication Date
WO2001062931A2 WO2001062931A2 (en) 2001-08-30
WO2001062931A3 true WO2001062931A3 (en) 2002-05-02

Family

ID=22679306

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/005923 Ceased WO2001062931A2 (en) 2000-02-25 2001-02-23 ANTI-EGFRvIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF

Country Status (22)

Country Link
US (1) US7129332B2 (en)
EP (1) EP1266009B1 (en)
JP (1) JP2003523771A (en)
KR (1) KR100812658B1 (en)
CN (1) CN1427891A (en)
AT (1) ATE419354T1 (en)
AU (2) AU2001239857B9 (en)
BG (1) BG106998A (en)
BR (1) BR0108646A (en)
CA (1) CA2400868C (en)
DE (1) DE60137202D1 (en)
HR (1) HRP20020769A2 (en)
HU (1) HUP0204142A3 (en)
MX (1) MXPA02008178A (en)
NO (1) NO20024034L (en)
NZ (1) NZ520622A (en)
PL (1) PL357448A1 (en)
RU (1) RU2317999C2 (en)
SK (1) SK12232002A3 (en)
UA (1) UA77157C2 (en)
WO (1) WO2001062931A2 (en)
YU (1) YU63302A (en)

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US8841417B2 (en) 2010-05-14 2014-09-23 Abbvie Inc. IL-1 binding proteins
US8852586B2 (en) 2004-11-12 2014-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
US8937158B2 (en) 2003-03-03 2015-01-20 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
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US10280227B2 (en) 2009-09-11 2019-05-07 Genentech, Inc. Highly concentrated pharmaceutical formulations

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