WO2004046330A3 - Methods of generating high-production of antibodies from hybridomas created by in vitro immunization - Google Patents

Methods of generating high-production of antibodies from hybridomas created by in vitro immunization Download PDF

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Publication number
WO2004046330A3
WO2004046330A3 PCT/US2003/036702 US0336702W WO2004046330A3 WO 2004046330 A3 WO2004046330 A3 WO 2004046330A3 US 0336702 W US0336702 W US 0336702W WO 2004046330 A3 WO2004046330 A3 WO 2004046330A3
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WO
WIPO (PCT)
Prior art keywords
cells
antibodies
mismatch repair
methods
affinity antibodies
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PCT/US2003/036702
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French (fr)
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WO2004046330A2 (en
Inventor
Luigi Grasso
Shaohong Liang
Nicholas E Nicolaides
Philip M Sass
Original Assignee
Morphotek Inc
Luigi Grasso
Shaohong Liang
Nicholas E Nicolaides
Philip M Sass
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 Morphotek Inc, Luigi Grasso, Shaohong Liang, Nicholas E Nicolaides, Philip M Sass filed Critical Morphotek Inc
Priority to AU2003295576A priority Critical patent/AU2003295576B2/en
Priority to JP2004570421A priority patent/JP4555089B2/en
Priority to DE60329526T priority patent/DE60329526D1/en
Priority to AT03786774T priority patent/ATE444359T1/en
Priority to CA2506127A priority patent/CA2506127C/en
Priority to EP20030786774 priority patent/EP1572971B1/en
Publication of WO2004046330A2 publication Critical patent/WO2004046330A2/en
Publication of WO2004046330A3 publication Critical patent/WO2004046330A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/01—Preparation of mutants without inserting foreign genetic material therein; Screening processes therefor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1282—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Clostridium (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/243—Colony Stimulating Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • C12N15/1024—In vivo mutagenesis using high mutation rate "mutator" host strains by inserting genetic material, e.g. encoding an error prone polymerase, disrupting a gene for mismatch repair
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The invention provides methods for generating high titers of high-affinity antibodies from hybridoma cells produced by fusing myeloma cells with in vitro immunized donor cells. The hybridoma cells or mammalian expression cells with cloned antibody genes from the hybridomas producing the high-affinity antibodies may be mismatch repair defective due to defects of endogenous mismatch repair subunits of through expression of a dominant negative allele of a mismatch repair gene which allows the hybridoma cell to be hypermutable, may be rendered hypermutable by chemical means, or may be naturally mismatch repair deficient. High-affinity antibodies and high titer producer cells producing antibodies may be prepared by the methods of the invention.
PCT/US2003/036702 2002-11-15 2003-11-14 Methods of generating high-production of antibodies from hybridomas created by in vitro immunization WO2004046330A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
AU2003295576A AU2003295576B2 (en) 2002-11-15 2003-11-14 Methods of generating high-production of antibodies from hybridomas created by in vitro immunization
JP2004570421A JP4555089B2 (en) 2002-11-15 2003-11-14 Method for producing high production amount of antibody from hybridoma created by in vitro immunization
DE60329526T DE60329526D1 (en) 2002-11-15 2003-11-14 METHOD OF GENERATING HIGH ANTIBODY PRODUCTION OF HYBRIDOMAS RESULTING FROM IN VITRO IMMUNIZATION
AT03786774T ATE444359T1 (en) 2002-11-15 2003-11-14 METHOD FOR GENERATING HIGH ANTIBODIES PRODUCTION FROM HYBRIDOMAS CREATED BY IN VITRO IMMUNIZATION
CA2506127A CA2506127C (en) 2002-11-15 2003-11-14 Methods of generating high-production of antibodies from hybridomas created by in vitro immunization
EP20030786774 EP1572971B1 (en) 2002-11-15 2003-11-14 Methods of generating high-production of antibodies from hybridomas created by in vitro immunization

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US42716502P 2002-11-15 2002-11-15
US60/427,165 2002-11-15
US50165003P 2003-09-10 2003-09-10
US60/501,650 2003-09-10

Publications (2)

Publication Number Publication Date
WO2004046330A2 WO2004046330A2 (en) 2004-06-03
WO2004046330A3 true WO2004046330A3 (en) 2006-09-28

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/036702 WO2004046330A2 (en) 2002-11-15 2003-11-14 Methods of generating high-production of antibodies from hybridomas created by in vitro immunization

Country Status (8)

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US (2) US7754450B2 (en)
EP (1) EP1572971B1 (en)
JP (1) JP4555089B2 (en)
AT (1) ATE444359T1 (en)
AU (1) AU2003295576B2 (en)
CA (1) CA2506127C (en)
DE (1) DE60329526D1 (en)
WO (1) WO2004046330A2 (en)

Families Citing this family (15)

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Publication number Priority date Publication date Assignee Title
US6982169B2 (en) * 2001-01-15 2006-01-03 Morphotek, Inc. Chemical inhibitors of mismatch repair
WO2004046330A2 (en) 2002-11-15 2004-06-03 Morphotek, Inc. Methods of generating high-production of antibodies from hybridomas created by in vitro immunization
ES2527428T3 (en) 2005-05-18 2015-01-23 Morphosys Ag Anti-GM-CSF antibodies and uses thereof
KR101486183B1 (en) 2006-02-08 2015-01-28 모르포테크, 인크. Antigenic gm-csf peptides and antibodies to gm-csf
AU2013201228B2 (en) * 2006-02-08 2016-01-21 Eisai, Inc. Antigenic gm-csf peptides and antibodies to gm-csf
WO2007121396A2 (en) * 2006-04-17 2007-10-25 Morphotek, Inc. Whole genome evolution technology applied to improve protein and antibody yields by cells
EP2126105A4 (en) 2007-02-20 2010-11-03 Anaptysbio Inc Somatic hypermutation systems
US20100248971A1 (en) * 2007-12-03 2010-09-30 Takashi Inagaki Process for antibody production
EP2289937A1 (en) * 2009-08-24 2011-03-02 Wilfried Stücker Production of monoclonal antibodies in vitro
WO2011159959A2 (en) * 2010-06-16 2011-12-22 Cdi Laboratories Methods and systems for generating, validating and using monoclonal antibodies
EP2890787B1 (en) * 2012-08-31 2019-05-01 Synthetic Genomics, Inc. Crowding agent-induced nucleic acid transfer into a recipient host cell
US10260089B2 (en) 2012-10-29 2019-04-16 The Research Foundation Of The State University Of New York Compositions and methods for recognition of RNA using triple helical peptide nucleic acids
AP2015008732A0 (en) * 2013-03-15 2015-09-30 Amgen Inc Human pac1 antibodies
WO2014144170A1 (en) * 2013-03-15 2014-09-18 The Cleveland Clinic Foundation In-vitro method for monoclonal antibody production using non-human act1 -deficient mice
CN110776564B (en) * 2019-10-30 2022-02-08 西北农林科技大学 Two-strain anti-newcastle disease virus nano antibody and expression preparation method and application thereof

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