CN101155832B - 抗体的改良方法 - Google Patents
抗体的改良方法 Download PDFInfo
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- CN101155832B CN101155832B CN2006800113520A CN200680011352A CN101155832B CN 101155832 B CN101155832 B CN 101155832B CN 2006800113520 A CN2006800113520 A CN 2006800113520A CN 200680011352 A CN200680011352 A CN 200680011352A CN 101155832 B CN101155832 B CN 101155832B
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- C—CHEMISTRY; METALLURGY
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- C07K16/46—Hybrid immunoglobulins
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- 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
- C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
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- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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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
- C12N15/09—Recombinant DNA-technology
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- 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
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Abstract
Description
突变体 | 与野生型的比较(%) |
P12S | 140 |
P12H | 150 |
P12V | 270 |
P12G | 230 |
P12L | 250 |
P12R | 190 |
P12F | 170 |
P12M | 140 |
P12E | 210 |
突变体 | 与野生型的比较(%) |
P18F | 180 |
P18A | 160 |
P18W | 200 |
P18L | 150 |
P18R | 160 |
P18Q | 170 |
P18S | 140 |
Claims (21)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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JP2005032377 | 2005-02-08 | ||
JP032377/2005 | 2005-02-08 | ||
PCT/JP2006/302036 WO2006085518A1 (ja) | 2005-02-08 | 2006-02-07 | 抗体の改良方法 |
Publications (2)
Publication Number | Publication Date |
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CN101155832A CN101155832A (zh) | 2008-04-02 |
CN101155832B true CN101155832B (zh) | 2013-02-06 |
Family
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CN2006800113520A Expired - Fee Related CN101155832B (zh) | 2005-02-08 | 2006-02-07 | 抗体的改良方法 |
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US (2) | US9873730B2 (zh) |
EP (2) | EP2395026B1 (zh) |
JP (2) | JP5142707B2 (zh) |
KR (1) | KR101262058B1 (zh) |
CN (1) | CN101155832B (zh) |
AU (1) | AU2006213321B2 (zh) |
CA (1) | CA2596925C (zh) |
WO (1) | WO2006085518A1 (zh) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2653661A1 (en) * | 2006-05-31 | 2007-12-06 | Astellas Pharma Inc. | Humanized anti-human osteopontin antibody |
GB0621513D0 (en) * | 2006-10-30 | 2006-12-06 | Domantis Ltd | Novel polypeptides and uses thereof |
ES2619943T3 (es) * | 2007-01-03 | 2017-06-27 | Morphotek, Inc. | Anticuerpos de alta afinidad que neutralizan la enterotoxina B estafilocócica |
AU2012241059B2 (en) * | 2007-01-03 | 2014-11-13 | Eisai, Inc. | High affinity antibodies that neutralize Staphylococcus enterotoxin B |
SI2681244T1 (en) * | 2011-03-02 | 2018-03-30 | Roche Glycart Ag | PROTITELESA CEA |
EA201892619A1 (ru) | 2011-04-29 | 2019-04-30 | Роше Гликарт Аг | Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2 |
WO2013056851A2 (en) * | 2011-10-20 | 2013-04-25 | Esbatech - A Novartis Company Llc | Stable multiple antigen-binding antibody |
EP3539563A1 (en) * | 2012-07-19 | 2019-09-18 | Redwood Bioscience, Inc. | Antibody specific for cd22 and methods of use thereof |
SG10201800982QA (en) * | 2013-07-05 | 2018-03-28 | Genmab As | Humanized or chimeric cd3 antibodies |
EP3632930A1 (en) * | 2013-08-30 | 2020-04-08 | Aprilbio Co., Ltd | An anti serum albumin fab-effector moiety fusion construct |
BR112016017597A2 (pt) | 2014-01-31 | 2017-08-08 | Aimm Therapeutics Bv | Métodos para produzir uma célula b, para selecionar pelo menos uma célula b, para produzir anticorpos específicos para um antígeno de interesse e para identificar pelo menos uma mutação na sequência de aminoácido da cadeia pesada e/ou cadeia leve de um anticorpo |
RU2019142330A (ru) | 2017-06-30 | 2021-07-30 | Займворкс, Инк. | Стабилизированные химерные fab |
JP7117088B2 (ja) * | 2017-08-04 | 2022-08-12 | シスメックス株式会社 | 抗体及びその製造方法、並びに抗体の熱安定性を向上させる方法 |
KR102115300B1 (ko) * | 2018-06-01 | 2020-05-26 | 재단법인 목암생명과학연구소 | 항체 라이브러리 및 이를 이용한 항체 스크리닝 방법 |
WO2024034638A1 (ja) * | 2022-08-10 | 2024-02-15 | 協和キリン株式会社 | 抗fgf23抗体又は該抗体断片 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4425115A1 (de) * | 1994-07-15 | 1996-01-18 | Boehringer Mannheim Gmbh | Verfahren zur Modifizierung der Stabilität von Antikörpern |
DE69726003T2 (de) * | 1996-07-16 | 2004-08-26 | Andreas Plückthun | Immunglobulin-superfamilie domainen und fragmente mit erhöhter löslichkeit |
WO1998010070A1 (fr) | 1996-09-02 | 1998-03-12 | Sumitomo Electric Industries, Ltd. | IMMUNOGLOBULINE HUMANISEE REAGISSANT SPECIFIQUEMENT AVEC UN LIGAND Fas OU L'UN DE SES FRAGMENTS ACTIFS ET REGION D'INDUCTION D'APOPTOSE PRENANT NAISSANCE DANS UN LIGAND Fas |
MXPA02001911A (es) * | 1999-08-24 | 2003-07-21 | Medarex Inc | Anticuerpos ctla-4 humanos y sus usos. |
WO2003008451A2 (en) | 2001-07-19 | 2003-01-30 | Universität Zürich | Modification of human variable domains |
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2006
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- 2006-02-07 JP JP2007502602A patent/JP5142707B2/ja not_active Expired - Fee Related
- 2006-02-07 KR KR1020077019945A patent/KR101262058B1/ko active IP Right Grant
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- 2006-02-07 EP EP06713179.7A patent/EP1860120B1/en not_active Not-in-force
- 2006-02-07 WO PCT/JP2006/302036 patent/WO2006085518A1/ja active Application Filing
- 2006-02-07 CA CA2596925A patent/CA2596925C/en not_active Expired - Fee Related
- 2006-02-07 US US11/815,838 patent/US9873730B2/en not_active Expired - Fee Related
- 2006-02-07 AU AU2006213321A patent/AU2006213321B2/en not_active Ceased
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2011
- 2011-11-14 JP JP2011248541A patent/JP5947022B2/ja not_active Expired - Fee Related
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2017
- 2017-12-11 US US15/837,569 patent/US10487137B2/en not_active Expired - Fee Related
Non-Patent Citations (7)
Title |
---|
Boris Steipe.Sequence Statistics Reliably Predict Stabilizing Mutations in a Protein Domain.《Journal of Molecular Biology》.1994, * |
Cox JP,.A directory of human germ-line V kappa segments reveals a strong bias in their usage..《< * |
Cox JP,.A directory of human germ-line V kappa segments reveals a strong bias in their usage..《<Eur J Immunol.》.1994, |
Eur J Immunol.》.1994, * |
Jager M.The rate-limiting steps for the folding of an antibody scFv fragment..《FEBS Lett.》.1997, * |
Ohage EC.Beta-turn propensities as paradigms for the analysis of structural motifs to engineer protein stability..《Protein Sci.》.1997, * |
THOMAS HESTERKAMP.Escherichia coli trigger factor is a prolyl isomerase that associates with nascent polypeptide chains.《Proc. Natl. Acad. Sci》.1996, * |
Also Published As
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AU2006213321A2 (en) | 2006-08-17 |
CN101155832A (zh) | 2008-04-02 |
KR20070102587A (ko) | 2007-10-18 |
US20080138860A1 (en) | 2008-06-12 |
KR101262058B1 (ko) | 2013-05-08 |
JP2012031211A (ja) | 2012-02-16 |
JP5142707B2 (ja) | 2013-02-13 |
AU2006213321B2 (en) | 2011-08-18 |
US9873730B2 (en) | 2018-01-23 |
US20180118813A1 (en) | 2018-05-03 |
EP1860120A1 (en) | 2007-11-28 |
CA2596925A1 (en) | 2006-08-17 |
JP5947022B2 (ja) | 2016-07-06 |
EP1860120A4 (en) | 2009-07-01 |
JPWO2006085518A1 (ja) | 2008-08-07 |
WO2006085518A1 (ja) | 2006-08-17 |
EP2395026B1 (en) | 2018-01-24 |
AU2006213321A1 (en) | 2006-08-17 |
EP2395026A3 (en) | 2011-12-21 |
US10487137B2 (en) | 2019-11-26 |
EP1860120B1 (en) | 2018-01-24 |
CA2596925C (en) | 2017-07-04 |
EP2395026A2 (en) | 2011-12-14 |
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