CA2035384A1 - Preparation and use of gene banks of synthetic human antibodies ("synthetic human-antibody libraries") - Google Patents
Preparation and use of gene banks of synthetic human antibodies ("synthetic human-antibody libraries")Info
- Publication number
- CA2035384A1 CA2035384A1 CA002035384A CA2035384A CA2035384A1 CA 2035384 A1 CA2035384 A1 CA 2035384A1 CA 002035384 A CA002035384 A CA 002035384A CA 2035384 A CA2035384 A CA 2035384A CA 2035384 A1 CA2035384 A1 CA 2035384A1
- Authority
- CA
- Canada
- Prior art keywords
- huab
- synthetic human
- synthetic
- preparation
- gene banks
- 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.)
- Granted
Links
Classifications
-
- 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
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
-
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
- C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/65—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression using markers
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/88—Lyases (4.)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/033—Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the internal surface of the plasma membrane, e.g. containing a myristoylation motif
Abstract
The invention relates to the preparation and use of gene banks of synthetic human antibodies (huAb) or parts of antibodies which contain the antigen-binding domain.
Starting from a huAb framework in a suitable vector, the hypervariable regions of the antibody cDNA are formed by almost "randomly" combined oligonucleotides. Relatively conserved amino acids in the hypervariable regions have here been taken account of in the choice of appropriate nucleotides during the oligonucleotide synthesis and the ratio of the nucleotides used is likewise chosen such that a nonsense codon is to be expected at most in every 89th position. Expression of this synthetic huAb cDNA in microbial expression systems, e.g. in E, coli in the vector pFMT which is described below, thus makes a synthetic huAb library with a comprehensive repertoire for screening using selected antigens available in vitro.
Starting from a huAb framework in a suitable vector, the hypervariable regions of the antibody cDNA are formed by almost "randomly" combined oligonucleotides. Relatively conserved amino acids in the hypervariable regions have here been taken account of in the choice of appropriate nucleotides during the oligonucleotide synthesis and the ratio of the nucleotides used is likewise chosen such that a nonsense codon is to be expected at most in every 89th position. Expression of this synthetic huAb cDNA in microbial expression systems, e.g. in E, coli in the vector pFMT which is described below, thus makes a synthetic huAb library with a comprehensive repertoire for screening using selected antigens available in vitro.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4002897A DE4002897A1 (en) | 1990-02-01 | 1990-02-01 | Synthetic human antibody library |
DEP4002897.6 | 1990-02-01 | ||
DE4003880A DE4003880A1 (en) | 1990-02-01 | 1990-02-09 | Synthetic human antibody library |
DEP4003880.7 | 1990-02-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2035384A1 true CA2035384A1 (en) | 1991-08-02 |
CA2035384C CA2035384C (en) | 2003-07-08 |
Family
ID=25889601
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002035384A Expired - Lifetime CA2035384C (en) | 1990-02-01 | 1991-01-31 | Preparation and use of gene banks of synthetic human antibodies ("synthetic human-antibody libraries") |
Country Status (13)
Country | Link |
---|---|
US (1) | US5840479A (en) |
EP (1) | EP0440146B1 (en) |
JP (1) | JPH04211395A (en) |
KR (1) | KR100221897B1 (en) |
AT (1) | ATE145427T1 (en) |
AU (1) | AU638535B2 (en) |
CA (1) | CA2035384C (en) |
DE (3) | DE4002897A1 (en) |
DK (1) | DK0440146T3 (en) |
ES (1) | ES2097157T3 (en) |
GR (1) | GR3022131T3 (en) |
IE (1) | IE75220B1 (en) |
PT (1) | PT96624B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5316922A (en) * | 1992-04-15 | 1994-05-31 | The United States Of America As Represented By Department Of Health And Human Services | Method for indentifying and expressing proteins that recognize and adhere to specific probes |
US5876961A (en) * | 1991-07-15 | 1999-03-02 | Glaxo Wellcome Inc. | Production of antibodies |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7063943B1 (en) | 1990-07-10 | 2006-06-20 | Cambridge Antibody Technology | Methods for producing members of specific binding pairs |
US6916605B1 (en) * | 1990-07-10 | 2005-07-12 | Medical Research Council | Methods for producing members of specific binding pairs |
GB9015198D0 (en) * | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
PT1696031E (en) * | 1991-12-02 | 2010-06-25 | Medical Res Council | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
US20010053523A1 (en) * | 1995-06-02 | 2001-12-20 | M&E Biotech A/S. | Method for identification of biologically active peptides and nucleic acids |
WO1996038553A1 (en) * | 1995-06-02 | 1996-12-05 | M&E Biotech A/S | A method for identification of biologically active peptides and nucleic acids |
US6828422B1 (en) | 1995-08-18 | 2004-12-07 | Morphosys Ag | Protein/(poly)peptide libraries |
DK1143006T3 (en) * | 1995-08-18 | 2008-07-14 | Morphosys Ip Gmbh | Vectors / DNA sequences from human combinatorial antibody libraries |
US6365344B1 (en) * | 1996-01-23 | 2002-04-02 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for screening for transdominant effector peptides and RNA molecules |
US6455247B1 (en) | 1996-01-23 | 2002-09-24 | Board Of Trustees Of The Leland Stanford Junior University | Methods for screening for transdominant effector peptides and RNA molecules |
US7087420B1 (en) | 1997-07-17 | 2006-08-08 | Cambia | Microbial β-glucuronidase genes, gene products and uses thereof |
US6391547B1 (en) * | 1997-09-09 | 2002-05-21 | Center For The Application Of Molecular Biology To International Agriculture | Microbial β-glucuronidase genes, gene products and uses thereof |
US6864235B1 (en) * | 1999-04-01 | 2005-03-08 | Eva A. Turley | Compositions and methods for treating cellular response to injury and other proliferating cell disorders regulated by hyaladherin and hyaluronans |
US6911429B2 (en) * | 1999-04-01 | 2005-06-28 | Transition Therapeutics Inc. | Compositions and methods for treating cellular response to injury and other proliferating cell disorders regulated by hyaladherin and hyaluronans |
IL130225A0 (en) | 1999-05-31 | 2000-06-01 | Yissum Res Dev Co | Novel uses of antibodies against ache and peptides thereof |
ES2531551T3 (en) * | 2000-04-17 | 2015-03-17 | Dyax Corp. | Methods for building genetic package presentation libraries for members of a diverse peptide family |
US8288322B2 (en) | 2000-04-17 | 2012-10-16 | Dyax Corp. | Methods of constructing libraries comprising displayed and/or expressed members of a diverse family of peptides, polypeptides or proteins and the novel libraries |
US20020110843A1 (en) * | 2000-05-12 | 2002-08-15 | Dumas David P. | Compositions and methods for epitope mapping |
WO2002061071A2 (en) | 2000-12-18 | 2002-08-08 | Dyax Corp. | Focused libraries of genetic packages |
US20040259783A1 (en) * | 2001-11-09 | 2004-12-23 | Tony Cruz | Pharmaceutical compositions of marine sponge microciona prolifera |
DE60232688D1 (en) * | 2001-11-20 | 2009-07-30 | Univ Duke | BOUNDARY-BIOMATERIALS |
KR100528772B1 (en) * | 2002-08-02 | 2005-11-15 | 주식회사유한양행 | A lambda light chain expression vector |
KR100604038B1 (en) * | 2002-08-02 | 2006-07-24 | 주식회사유한양행 | A heavy chain expression vector |
KR100604037B1 (en) * | 2002-08-02 | 2006-07-24 | 주식회사유한양행 | A kafa light chain expression vector |
WO2004013278A2 (en) * | 2002-08-02 | 2004-02-12 | Yuhan Corporation | Expression vectors |
US20040067532A1 (en) | 2002-08-12 | 2004-04-08 | Genetastix Corporation | High throughput generation and affinity maturation of humanized antibody |
CN100406554C (en) * | 2003-03-28 | 2008-07-30 | 广州医学院 | Colibacillus containing human source guide suppository dissolving antibody gene and its secretion producg |
ATE462451T1 (en) | 2004-06-16 | 2010-04-15 | Affinergy Inc | INTERFACE BIOMATERIALS TO PROMOTE ADHESION OF TARGET ANALYTES |
US20120208824A1 (en) | 2006-01-20 | 2012-08-16 | Cell Signaling Technology, Inc. | ROS Kinase in Lung Cancer |
EP1973946B1 (en) | 2006-01-20 | 2015-03-25 | Cell Signaling Technology, Inc. | Translocation and mutant ros kinase in human non-small cell lung carcinoma |
WO2007092777A2 (en) * | 2006-02-02 | 2007-08-16 | Wyeth | Cloning, characterization, and application of tnfrsf19 in neurological disorders |
HUE035732T2 (en) | 2006-04-14 | 2018-05-28 | Cell Signaling Technology Inc | Gene defects and mutant ALK kinase in human solid tumors |
US20090252745A1 (en) * | 2006-09-15 | 2009-10-08 | Duke University | Amino acids in the HCV core polypeptide domain 3 and correlation with steatosis |
US8877688B2 (en) | 2007-09-14 | 2014-11-04 | Adimab, Llc | Rationally designed, synthetic antibody libraries and uses therefor |
WO2009036379A2 (en) * | 2007-09-14 | 2009-03-19 | Adimab, Inc. | Rationally designed, synthetic antibody libraries and uses therefor |
EP2203558B1 (en) | 2007-10-18 | 2016-05-04 | Cell Signaling Technology, Inc. | Translocation and mutant ros kinase in human non-small cell lung carcinoma |
WO2009114815A1 (en) | 2008-03-13 | 2009-09-17 | Dyax Corp | Libraries of genetic packages comprising novel hc cdr3 designs |
EP2281078B1 (en) * | 2008-04-24 | 2014-10-22 | Dyax Corporation | Libraries of genetic packages comprising novel hc cdr1, cdr2, and cdr3 and novel lc cdr1, cdr2, and cdr3 designs |
CN101768213B (en) | 2008-12-30 | 2012-05-30 | 中国科学院遗传与发育生物学研究所 | Protein related to plant tillering number and coding gene and application thereof |
HUE035769T2 (en) | 2009-02-12 | 2018-05-28 | Cell Signaling Technology Inc | Mutant ROS expression in human liver cancer |
CN101817879A (en) | 2009-02-26 | 2010-09-01 | 中国科学院遗传与发育生物学研究所 | Metallothionein and encoding gene and application thereof |
DK2435568T3 (en) | 2009-05-29 | 2014-09-08 | Morphosys Ag | Collection of synthetic antibodies to treat disease |
CA2773564A1 (en) * | 2009-09-14 | 2011-03-17 | Dyax Corp. | Libraries of genetic packages comprising novel hc cdr3 designs |
CN102326199B (en) | 2009-12-22 | 2014-11-05 | 松下电器产业株式会社 | Optical disc device, optical disc control method, and integrated circuit |
DK3741883T3 (en) | 2010-07-16 | 2023-02-20 | Adimab Llc | ANTIBODIES LIBRARIES |
US20120101108A1 (en) | 2010-08-06 | 2012-04-26 | Cell Signaling Technology, Inc. | Anaplastic Lymphoma Kinase In Kidney Cancer |
ES2696548T3 (en) | 2010-11-19 | 2019-01-16 | Morphosys Ag | A collection of antibody sequences and their use |
HUE037856T2 (en) | 2012-04-18 | 2018-09-28 | Cell Signaling Technology Inc | Egfr and ros1 in cancer |
SG11202001551YA (en) | 2017-08-21 | 2020-03-30 | Adagene Inc | Dynamic human heavy chain antibody libraries |
KR20200054209A (en) | 2017-08-21 | 2020-05-19 | 아다진 인크. | Dynamic human antibody light chain library |
US20230303666A1 (en) * | 2020-09-24 | 2023-09-28 | The Broad Institute, Inc. | Cell-free antibody engineering platform and neutralizing antibodies for sars-cov-2 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE114723T1 (en) * | 1987-03-02 | 1994-12-15 | Enzon Lab Inc | ORGANISM AS CARRIER FOR ''SINGLE CHAIN ANTIBODY DOMAIN (SCAD)''. |
-
1990
- 1990-02-01 DE DE4002897A patent/DE4002897A1/en not_active Withdrawn
- 1990-02-09 DE DE4003880A patent/DE4003880A1/en not_active Withdrawn
-
1991
- 1991-01-28 DE DE59108350T patent/DE59108350D1/en not_active Expired - Lifetime
- 1991-01-28 EP EP91101094A patent/EP0440146B1/en not_active Expired - Lifetime
- 1991-01-28 ES ES91101094T patent/ES2097157T3/en not_active Expired - Lifetime
- 1991-01-28 AT AT91101094T patent/ATE145427T1/en not_active IP Right Cessation
- 1991-01-28 DK DK91101094.0T patent/DK0440146T3/en active
- 1991-01-31 AU AU70115/91A patent/AU638535B2/en not_active Expired
- 1991-01-31 IE IE33691A patent/IE75220B1/en not_active IP Right Cessation
- 1991-01-31 PT PT96624A patent/PT96624B/en not_active IP Right Cessation
- 1991-01-31 CA CA002035384A patent/CA2035384C/en not_active Expired - Lifetime
- 1991-02-01 JP JP3032216A patent/JPH04211395A/en active Pending
- 1991-02-01 KR KR1019910001732A patent/KR100221897B1/en not_active IP Right Cessation
-
1994
- 1994-12-02 US US08/353,372 patent/US5840479A/en not_active Expired - Lifetime
-
1996
- 1996-12-20 GR GR960403569T patent/GR3022131T3/en unknown
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5876961A (en) * | 1991-07-15 | 1999-03-02 | Glaxo Wellcome Inc. | Production of antibodies |
US5316922A (en) * | 1992-04-15 | 1994-05-31 | The United States Of America As Represented By Department Of Health And Human Services | Method for indentifying and expressing proteins that recognize and adhere to specific probes |
Also Published As
Publication number | Publication date |
---|---|
DK0440146T3 (en) | 1997-03-10 |
JPH04211395A (en) | 1992-08-03 |
CA2035384C (en) | 2003-07-08 |
AU638535B2 (en) | 1993-07-01 |
KR910021474A (en) | 1991-12-20 |
DE4002897A1 (en) | 1991-08-08 |
US5840479A (en) | 1998-11-24 |
ES2097157T3 (en) | 1997-04-01 |
EP0440146A2 (en) | 1991-08-07 |
EP0440146A3 (en) | 1992-07-15 |
DE4003880A1 (en) | 1991-08-14 |
AU7011591A (en) | 1991-08-08 |
IE75220B1 (en) | 1997-08-27 |
EP0440146B1 (en) | 1996-11-20 |
PT96624A (en) | 1991-11-29 |
KR100221897B1 (en) | 1999-10-01 |
GR3022131T3 (en) | 1997-03-31 |
ATE145427T1 (en) | 1996-12-15 |
DE59108350D1 (en) | 1997-01-02 |
IE910336A1 (en) | 1991-08-14 |
PT96624B (en) | 1998-07-31 |
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Legal Events
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EEER | Examination request | ||
MKEX | Expiry |