WO2003099999A3 - Generation and selection of protein library in silico - Google Patents

Generation and selection of protein library in silico Download PDF

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Publication number
WO2003099999A3
WO2003099999A3 PCT/US2003/016037 US0316037W WO03099999A3 WO 2003099999 A3 WO2003099999 A3 WO 2003099999A3 US 0316037 W US0316037 W US 0316037W WO 03099999 A3 WO03099999 A3 WO 03099999A3
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WO
WIPO (PCT)
Prior art keywords
library
lead
sequence
protein
proteins
Prior art date
Application number
PCT/US2003/016037
Other languages
French (fr)
Other versions
WO2003099999A2 (en
Inventor
Peizhi Luo
Mark Hsieh
Pingyu Zhong
Caili Wang
Yicheng Cao
Shengjiang Liu
Original Assignee
Abmaxis Inc
Peizhi Luo
Mark Hsieh
Pingyu Zhong
Caili Wang
Yicheng Cao
Shengjiang Liu
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 claimed from US10/153,176 external-priority patent/US20030022240A1/en
Priority claimed from US10/153,159 external-priority patent/US7117096B2/en
Application filed by Abmaxis Inc, Peizhi Luo, Mark Hsieh, Pingyu Zhong, Caili Wang, Yicheng Cao, Shengjiang Liu filed Critical Abmaxis Inc
Priority to EP03755415A priority Critical patent/EP1514216A4/en
Priority to CN038173603A priority patent/CN1672160B/en
Priority to JP2004508241A priority patent/JP2005526518A/en
Priority to CA002485732A priority patent/CA2485732A1/en
Priority to AU2003248548A priority patent/AU2003248548B2/en
Publication of WO2003099999A2 publication Critical patent/WO2003099999A2/en
Publication of WO2003099999A3 publication Critical patent/WO2003099999A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/30Detection of binding sites or motifs
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B30/00ICT specially adapted for sequence analysis involving nucleotides or amino acids
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B30/00ICT specially adapted for sequence analysis involving nucleotides or amino acids
    • G16B30/10Sequence alignment; Homology search
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B35/00ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B35/00ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
    • G16B35/20Screening of libraries
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16CCOMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/60In silico combinatorial chemistry
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/60Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622Single chain antibody (scFv)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/50Mutagenesis

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Theoretical Computer Science (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Biotechnology (AREA)
  • Evolutionary Biology (AREA)
  • Medical Informatics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Library & Information Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Computing Systems (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

The present invention provides a methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as improved binding affinity towards biologically and/or therapeutically important target molecules. The process is carried out computationally in a high throughput manner by mining the ever-expanding databases of protein sequences of all organisms, especially human. In one embodiment, a method for constructing a library of designed proteins, comprising the steps of: providing an amino acid sequence derived from a lead protein, the amino acid sequence being designated as a lead sequence; comparing the lead sequence with a plurality of tester protein sequences; and selecting from the plurality of tester protein sequences at least two peptide segments that have at least 15% sequence identity with the lead sequence, the selected peptide segments forming a hit library; and forming a library of designed proteins by substituting the lead sequence with the hit library. The library of designed proteins can be expressed in vitro or in vivo to produce a library of recombinant proteins that can be screened for novel or improved function(s) over the lead protein, such as an antibody against therapeutically important target.
PCT/US2003/016037 2002-05-20 2003-05-20 Generation and selection of protein library in silico WO2003099999A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP03755415A EP1514216A4 (en) 2002-05-20 2003-05-20 Generation and selection of protein library in silico
CN038173603A CN1672160B (en) 2002-05-20 2003-05-20 Method for constructing antibody library based on precursor antibody structure
JP2004508241A JP2005526518A (en) 2002-05-20 2003-05-20 Insilico creation and selection of protein libraries
CA002485732A CA2485732A1 (en) 2002-05-20 2003-05-20 Generation and selection of protein library in silico
AU2003248548A AU2003248548B2 (en) 2002-05-20 2003-05-20 Generation and selection of protein library in silico

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/153,176 US20030022240A1 (en) 2001-04-17 2002-05-20 Generation and affinity maturation of antibody library in silico
US10/153,159 2002-05-20
US10/153,159 US7117096B2 (en) 2001-04-17 2002-05-20 Structure-based selection and affinity maturation of antibody library
US10/153,176 2002-05-20

Publications (2)

Publication Number Publication Date
WO2003099999A2 WO2003099999A2 (en) 2003-12-04
WO2003099999A3 true WO2003099999A3 (en) 2004-09-16

Family

ID=29586304

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/016037 WO2003099999A2 (en) 2002-05-20 2003-05-20 Generation and selection of protein library in silico

Country Status (7)

Country Link
EP (1) EP1514216A4 (en)
JP (1) JP2005526518A (en)
CN (1) CN1672160B (en)
AU (1) AU2003248548B2 (en)
CA (1) CA2485732A1 (en)
SG (1) SG135053A1 (en)
WO (1) WO2003099999A2 (en)

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US7667004B2 (en) * 2001-04-17 2010-02-23 Abmaxis, Inc. Humanized antibodies against vascular endothelial growth factor
AU2004202566B2 (en) * 2004-06-11 2011-07-21 Li-Te Chin Method for Producing Human Antibodies with Properties of Agonist, Antagonist, or Inverse Agonist
RS20070027A (en) 2004-07-26 2008-11-28 Biogen Idec Ma Inc., Anti-cd154 antibodies
PT3540062T (en) 2004-11-16 2021-07-06 Humanigen Inc Immunoglobulin variable region cassette exchange
EP1869084A2 (en) 2005-03-04 2007-12-26 Biogen Idec MA Inc. Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues
NZ591252A (en) * 2006-03-17 2012-06-29 Biogen Idec Inc Methods of designing antibody or antigen binding fragments thereof with substituted non-covarying amino acids
JP5473603B2 (en) * 2006-10-02 2014-04-16 シー レーン バイオテクノロジーズ, エルエルシー Design and construction of diverse synthetic peptide and polypeptide libraries
CN101647022B (en) * 2007-01-31 2012-07-18 麦科罗医药科技(武汉)有限公司 Methods, systems and means for describing the protein conformations and for evaluating proteins conformations based on folding, overall shape and structural sequence
CA2742969A1 (en) * 2008-11-07 2010-05-14 Fabrus Llc Anti-dll4 antibodies and uses thereof
MX346002B (en) 2009-06-17 2017-03-01 Abbvie Biotherapeutics Inc Anti-vegf antibodies and their uses.
DK2488867T3 (en) * 2009-10-14 2020-11-09 Janssen Biotech Inc PROCEDURES FOR AFFINITY MATURE OF ANTIBODIES
WO2013171810A1 (en) 2012-05-14 2013-11-21 パナソニック株式会社 Method for obtaining heat-resistant antibody-presenting phage
US20140154255A1 (en) 2012-11-30 2014-06-05 Abbvie Biotherapeutics Inc. Anti-vegf antibodies and their uses
JP6377078B2 (en) * 2013-01-31 2018-08-22 コデクシス, インコーポレイテッド Method, system, and software for identifying biomolecules having interacting components
CN104805507B (en) * 2014-01-29 2019-01-22 杭州康万达医药科技有限公司 phage display library and its application and preparation method
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JP6558754B2 (en) 2015-08-07 2019-08-14 富士通株式会社 Information processing apparatus, index dimension extraction method, and index dimension extraction program
CN116987187A (en) 2015-09-23 2023-11-03 豪夫迈·罗氏有限公司 Optimized variants of anti-VEGF antibodies
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CN106905435B (en) * 2017-03-13 2020-04-10 武汉海沙百得生物技术有限公司 Method for preparing binding protein based on protein A mutant
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WO2019036055A2 (en) * 2017-08-18 2019-02-21 Ignite Biosciences, Inc. Methods of selecting binding reagents
KR102615744B1 (en) * 2017-11-20 2023-12-19 난트바이오 인코포레이티드 mRNA DISPLAY ANTIBODY LIBRARY AND METHODS
CN108304691B (en) * 2018-02-09 2021-05-18 北京矿冶科技集团有限公司 Fragment-based flotation agent molecule design method
CN108491692B (en) * 2018-03-09 2023-07-21 中国科学院生态环境研究中心 Method for constructing antibiotic resistance gene database
CN108763870B (en) * 2018-05-09 2021-08-03 浙江工业大学 Construction method of multi-domain protein Linker
CN109002690B (en) * 2018-06-08 2021-05-18 济南大学 Method for predicting side chain structure of mutant amino acid by constructing CHARMM ROTAMERS force field
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Also Published As

Publication number Publication date
EP1514216A2 (en) 2005-03-16
WO2003099999A2 (en) 2003-12-04
AU2003248548A1 (en) 2003-12-12
EP1514216A4 (en) 2010-01-06
AU2003248548B2 (en) 2010-03-11
CN1672160B (en) 2010-06-09
CA2485732A1 (en) 2003-12-04
CN1672160A (en) 2005-09-21
JP2005526518A (en) 2005-09-08
SG135053A1 (en) 2007-09-28

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