WO2004024871A3 - Antibodies and methods for generating genetically altered antibodies with high affinity - Google Patents

Antibodies and methods for generating genetically altered antibodies with high affinity Download PDF

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Publication number
WO2004024871A3
WO2004024871A3 PCT/US2003/028722 US0328722W WO2004024871A3 WO 2004024871 A3 WO2004024871 A3 WO 2004024871A3 US 0328722 W US0328722 W US 0328722W WO 2004024871 A3 WO2004024871 A3 WO 2004024871A3
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WO
WIPO (PCT)
Prior art keywords
antibodies
methods
useful
genes
cells
Prior art date
Application number
PCT/US2003/028722
Other languages
French (fr)
Other versions
WO2004024871A2 (en
Inventor
Luigi Grasso
Original Assignee
Morphotek Inc
Luigi Grasso
Nicolaides Nicholas E
Sass Philip M
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, Nicolaides Nicholas E, Sass Philip M filed Critical Morphotek Inc
Priority to AU2003272352A priority Critical patent/AU2003272352A1/en
Priority to EP03754530A priority patent/EP1556508A4/en
Priority to JP2004536226A priority patent/JP2006503035A/en
Priority to CA002544124A priority patent/CA2544124A1/en
Publication of WO2004024871A2 publication Critical patent/WO2004024871A2/en
Publication of WO2004024871A3 publication Critical patent/WO2004024871A3/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
    • C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
    • C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
    • 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
    • C07K2317/50—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
    • 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
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulins genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the affinity of monoclonal antibodies and monoclonal antibodies with increased affinity.
PCT/US2003/028722 2002-09-13 2003-09-12 Antibodies and methods for generating genetically altered antibodies with high affinity WO2004024871A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU2003272352A AU2003272352A1 (en) 2002-09-13 2003-09-12 Antibodies and methods for generating genetically altered antibodies with high affinity
EP03754530A EP1556508A4 (en) 2002-09-13 2003-09-12 Antibodies and methods for generating genetically altered antibodies with high affinity
JP2004536226A JP2006503035A (en) 2002-09-13 2003-09-12 Methods for producing antibodies and genetically modified antibodies with high affinity
CA002544124A CA2544124A1 (en) 2002-09-13 2003-09-12 Antibodies and methods for generating genetically altered antibodies with high affinity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/243,130 US7235643B2 (en) 2000-11-07 2002-09-13 Antibodies and methods for generating genetically altered antibodies with high affinity
US10/243,130 2002-09-13

Publications (2)

Publication Number Publication Date
WO2004024871A2 WO2004024871A2 (en) 2004-03-25
WO2004024871A3 true WO2004024871A3 (en) 2005-05-19

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/028722 WO2004024871A2 (en) 2002-09-13 2003-09-12 Antibodies and methods for generating genetically altered antibodies with high affinity

Country Status (6)

Country Link
US (2) US7235643B2 (en)
EP (1) EP1556508A4 (en)
JP (1) JP2006503035A (en)
AU (1) AU2003272352A1 (en)
CA (1) CA2544124A1 (en)
WO (1) WO2004024871A2 (en)

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US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity

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US7235643B2 (en) 2000-11-07 2007-06-26 Morphotek, Inc. Antibodies and methods for generating genetically altered antibodies with high affinity
US20070148171A1 (en) * 2002-09-27 2007-06-28 Xencor, Inc. Optimized anti-CD30 antibodies
US8093357B2 (en) * 2002-03-01 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US20080254027A1 (en) * 2002-03-01 2008-10-16 Bernett Matthew J Optimized CD5 antibodies and methods of using the same
US20080260731A1 (en) * 2002-03-01 2008-10-23 Bernett Matthew J Optimized antibodies that target cd19
US7317091B2 (en) * 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US8188231B2 (en) 2002-09-27 2012-05-29 Xencor, Inc. Optimized FC variants
US20060235208A1 (en) * 2002-09-27 2006-10-19 Xencor, Inc. Fc variants with optimized properties
CA2506127C (en) 2002-11-15 2013-07-09 Morphotek, Inc. Methods of generating high-production of antibodies from hybridomas created by in vitro immunization
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
US20090010920A1 (en) 2003-03-03 2009-01-08 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRIIb
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US20070275460A1 (en) * 2003-03-03 2007-11-29 Xencor.Inc. Fc Variants With Optimized Fc Receptor Binding Properties
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
AU2004248165A1 (en) * 2003-06-11 2004-12-23 Biogen Idec Ma Inc. Method to increase protein production in culture
CA2534077A1 (en) * 2003-07-29 2005-02-10 Morphotek Inc. Antibodies and methods for generating genetically altered antibodies with enhanced effector function
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
US20050249723A1 (en) * 2003-12-22 2005-11-10 Xencor, Inc. Fc polypeptides with novel Fc ligand binding sites
US7276585B2 (en) * 2004-03-24 2007-10-02 Xencor, Inc. Immunoglobulin variants outside the Fc region
CA2573505C (en) 2004-07-14 2013-06-25 Igeneon Krebs-Immuntherapie Forschungs-Und Entwicklungs-Ag N-glycosylated antibody
US20150010550A1 (en) 2004-07-15 2015-01-08 Xencor, Inc. OPTIMIZED Fc VARIANTS
US20060074225A1 (en) * 2004-09-14 2006-04-06 Xencor, Inc. Monomeric immunoglobulin Fc domains
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
KR101027427B1 (en) * 2004-11-12 2011-04-11 젠코어 인코포레이티드 Fc VARIANTS WITH INCREASED BINDING TO FcRn
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
US20060275282A1 (en) * 2005-01-12 2006-12-07 Xencor, Inc. Antibodies and Fc fusion proteins with altered immunogenicity
JP2009504685A (en) * 2005-08-15 2009-02-05 アラーナ・テラピューティクス・リミテッド Engineered antibodies using the New World primate framework region
CA2619245A1 (en) * 2005-08-15 2007-02-22 Arana Therapeutics Limited Chimeric antibodies with new world primate regions
DK1931709T3 (en) * 2005-10-03 2017-03-13 Xencor Inc FC VARIETIES WITH OPTIMIZED FC RECEPTOR BINDING PROPERTIES
JP4860703B2 (en) 2005-10-06 2012-01-25 ゼンコー・インコーポレイテッド Optimized anti-CD30 antibody
US20090286962A1 (en) * 2005-12-20 2009-11-19 Woolven Benjamin P Chimeric antibodies with part new world primate binding regions
EA017417B1 (en) * 2006-02-01 2012-12-28 Сефалон Астралия Пти Лтд. DOMAIN ANTIBODY CONSTRUCT WHICH BINDS TO HUMAN TNF-α AND USE THEREOF
CA2649698A1 (en) * 2006-04-17 2007-10-25 Morphotek, Inc. Whole genome evolution technology applied to improve protein and antibody yields by cells
AU2007285976B2 (en) 2006-08-14 2011-08-18 Xencor, Inc Optimized antibodies that target CD19
WO2008036688A2 (en) * 2006-09-18 2008-03-27 Xencor, Inc. Optimized antibodies that target hm1.24
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WO2008089355A1 (en) * 2007-01-17 2008-07-24 Life Technologies Corporation Methods and compositions for improving the health of cells in culture
US8603950B2 (en) 2007-02-20 2013-12-10 Anaptysbio, Inc. Methods of generating libraries and uses thereof
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EP2808343B8 (en) 2007-12-26 2020-01-15 Xencor, Inc. Fc variants with altered binding to FcRn
US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
HUE043556T2 (en) 2009-12-10 2019-09-30 Regeneron Pharma Mice that make heavy chain antibodies

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Publication number Priority date Publication date Assignee Title
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity

Also Published As

Publication number Publication date
US7671179B2 (en) 2010-03-02
US20030143682A1 (en) 2003-07-31
WO2004024871A2 (en) 2004-03-25
EP1556508A2 (en) 2005-07-27
AU2003272352A1 (en) 2004-04-30
US7235643B2 (en) 2007-06-26
CA2544124A1 (en) 2004-03-25
JP2006503035A (en) 2006-01-26
EP1556508A4 (en) 2006-10-04
US20070244302A1 (en) 2007-10-18

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