WO2009009045A3 - Escape libraries of target polypeptides - Google Patents

Escape libraries of target polypeptides Download PDF

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Publication number
WO2009009045A3
WO2009009045A3 PCT/US2008/008367 US2008008367W WO2009009045A3 WO 2009009045 A3 WO2009009045 A3 WO 2009009045A3 US 2008008367 W US2008008367 W US 2008008367W WO 2009009045 A3 WO2009009045 A3 WO 2009009045A3
Authority
WO
WIPO (PCT)
Prior art keywords
library
escape
target polypeptide
identified
variant polypeptides
Prior art date
Application number
PCT/US2008/008367
Other languages
French (fr)
Other versions
WO2009009045A2 (en
Inventor
Richard A. Lerner
Sydney Brenner
Tobin J. Dickerson
Kim D. Janda
Original Assignee
The Scripps Research Institute
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 The Scripps Research Institute filed Critical The Scripps Research Institute
Publication of WO2009009045A2 publication Critical patent/WO2009009045A2/en
Publication of WO2009009045A3 publication Critical patent/WO2009009045A3/en

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
    • 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
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1037—Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)

Abstract

The present invention provides methods for identifying escape variants of a target polypeptide. The methods typically involve generating a library of variant polypeptides of the target polypeptide on a replicable display platform (e.g., phage display), identifying variant polypeptides which maintain the ability to bind to a known binding partner of the target polypeptide, and examining the identified variant polypeptides to identify escape variants whose binding to the binding partner is not antagonized by a library of known compounds which disrupt binding between the target polypeptide and the binding partner. The methods can further entail screening a library of candidate antagonist agents to identify a cognate antagonist agent which antagonizes binding between the escape variant and the binding partner. Additional escape variants can be identified by creating a library of further variant polypeptides of the identified escape variant, and subject the further variant polypeptides to the screening process. In each subsequent round of screening, the identified antagonist agent is combined with the library of known compounds employed in the previous round of screening. The invention also provides related methods for identifying novel antagonist agents of a target polypeptide. Further provided are vectors and kits for displaying a functional multimeric target protein on the surface of a phage.
PCT/US2008/008367 2007-07-10 2008-07-08 Escape libraries of target polypeptides WO2009009045A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US95892507P 2007-07-10 2007-07-10
US60/958,925 2007-07-10

Publications (2)

Publication Number Publication Date
WO2009009045A2 WO2009009045A2 (en) 2009-01-15
WO2009009045A3 true WO2009009045A3 (en) 2010-03-18

Family

ID=40229342

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/008367 WO2009009045A2 (en) 2007-07-10 2008-07-08 Escape libraries of target polypeptides

Country Status (1)

Country Link
WO (1) WO2009009045A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9347058B2 (en) 2011-05-17 2016-05-24 Bristol-Myers Squibb Company Methods for the selection of binding proteins
TW201418707A (en) * 2012-09-21 2014-05-16 Alexion Pharma Inc Screening assays for complement component C5 antagonists
AU2015336308B2 (en) * 2014-10-20 2020-05-14 The Scripps Research Institute Proximity based methods for selection of binding partners

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5571836A (en) * 1992-11-09 1996-11-05 Bovin; Nicolai V. Viral attachment inhibitors
US6277489B1 (en) * 1998-12-04 2001-08-21 The Regents Of The University Of California Support for high performance affinity chromatography and other uses
US20050136428A1 (en) * 2003-06-27 2005-06-23 Roberto Crea Look-through mutagenesis
US6943000B2 (en) * 1997-10-03 2005-09-13 University Of Massachusetts JNK3 modulators and methods of use
US20060084608A1 (en) * 2000-08-18 2006-04-20 Human Genome Sciences, Inc. Binding polypeptides and methods based thereon
US7135287B1 (en) * 1999-10-02 2006-11-14 Biosite, Inc. Human antibodies

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5571836A (en) * 1992-11-09 1996-11-05 Bovin; Nicolai V. Viral attachment inhibitors
US6943000B2 (en) * 1997-10-03 2005-09-13 University Of Massachusetts JNK3 modulators and methods of use
US6277489B1 (en) * 1998-12-04 2001-08-21 The Regents Of The University Of California Support for high performance affinity chromatography and other uses
US7135287B1 (en) * 1999-10-02 2006-11-14 Biosite, Inc. Human antibodies
US20060084608A1 (en) * 2000-08-18 2006-04-20 Human Genome Sciences, Inc. Binding polypeptides and methods based thereon
US20050136428A1 (en) * 2003-06-27 2005-06-23 Roberto Crea Look-through mutagenesis

Also Published As

Publication number Publication date
WO2009009045A2 (en) 2009-01-15

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