ES2846732T3 - Método de monomerización de moléculas de anticuerpos recombinantes - Google Patents
Método de monomerización de moléculas de anticuerpos recombinantes Download PDFInfo
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- ES2846732T3 ES2846732T3 ES16719824T ES16719824T ES2846732T3 ES 2846732 T3 ES2846732 T3 ES 2846732T3 ES 16719824 T ES16719824 T ES 16719824T ES 16719824 T ES16719824 T ES 16719824T ES 2846732 T3 ES2846732 T3 ES 2846732T3
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Classifications
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1133—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by redox-reactions involving cystein/cystin side chains
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1136—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating or stabilising agents
-
- 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
- C07K16/2878—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 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/11—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/12—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
- C07K5/123—Tripeptides
Landscapes
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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|---|---|---|---|---|
| GB201223276D0 (en) * | 2012-12-21 | 2013-02-06 | Ucb Pharma Sa | Antibodies and methods of producing same |
| US10626143B2 (en) | 2014-12-22 | 2020-04-21 | Ucb Biopharma Sprl | Method of protein manufacture |
| GB201506869D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method |
| GB201506870D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method |
| GB201506868D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method for protein purification |
| MX2021003976A (es) * | 2018-10-11 | 2021-05-27 | Amgen Inc | Procesamiento posterior de constructos de anticuerpos biespecificos. |
| KR20210107731A (ko) * | 2018-12-21 | 2021-09-01 | 노파르티스 아게 | Pmel17에 대한 항체 및 이의 접합체 |
| IL303295A (en) * | 2020-12-07 | 2023-07-01 | UCB Biopharma SRL | Multi-specific antibodies and antibody combinations |
Family Cites Families (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| DK336987D0 (da) | 1987-07-01 | 1987-07-01 | Novo Industri As | Immobiliseringsmetode |
| US5453363A (en) | 1985-10-23 | 1995-09-26 | Boehringer Mannheim Gmbh | Process for the activation of t-PA or Ing after genetic expression in prokaryotes |
| GB8719042D0 (en) | 1987-08-12 | 1987-09-16 | Parker D | Conjugate compounds |
| GB8720833D0 (en) | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
| EP1997891A1 (en) | 1988-09-02 | 2008-12-03 | Dyax Corporation | Generation and selection of recombinant varied binding proteins |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| GB8907617D0 (en) | 1989-04-05 | 1989-05-17 | Celltech Ltd | Drug delivery system |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
| WO1991010737A1 (en) | 1990-01-11 | 1991-07-25 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| WO1992002551A1 (en) | 1990-08-02 | 1992-02-20 | B.R. Centre Limited | Methods for the production of proteins with a desired function |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| WO1992009690A2 (en) | 1990-12-03 | 1992-06-11 | Genentech, Inc. | Enrichment method for variant proteins with altered binding properties |
| DE69233750D1 (de) | 1991-04-10 | 2009-01-02 | Scripps Research Inst | Bibliotheken heterodimerer Rezeptoren mittels Phagemiden |
| GB9112536D0 (en) | 1991-06-11 | 1991-07-31 | Celltech Ltd | Chemical compounds |
| GB9120467D0 (en) | 1991-09-26 | 1991-11-06 | Celltech Ltd | Anti-hmfg antibodies and process for their production |
| ATE408012T1 (de) | 1991-12-02 | 2008-09-15 | Medical Res Council | Herstellung von autoantikörpern auf phagenoberflächen ausgehend von antikörpersegmentbibliotheken |
| ATE419355T1 (de) * | 1992-02-06 | 2009-01-15 | Novartis Vaccines & Diagnostic | Marker für krebs und biosynthetisches bindeprotein dafür |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| WO1995015982A2 (en) | 1993-12-08 | 1995-06-15 | Genzyme Corporation | Process for generating specific antibodies |
| DK1231268T3 (da) | 1994-01-31 | 2005-11-21 | Univ Boston | Polyklonale antistofbiblioteker |
| FR2716640B1 (fr) | 1994-02-28 | 1996-05-03 | Procedes Machines Speciales | Dispositif de centrage et de blocage d'une pièce en vue de son rodage à l'aide d'un rodoir à expansion. |
| US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
| JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
| US5980898A (en) | 1996-11-14 | 1999-11-09 | The United States Of America As Represented By The U.S. Army Medical Research & Material Command | Adjuvant for transcutaneous immunization |
| GB9625640D0 (en) | 1996-12-10 | 1997-01-29 | Celltech Therapeutics Ltd | Biological products |
| ES2366100T3 (es) * | 1999-02-22 | 2011-10-17 | Georgetown University | Inmunoliposomas dirigidos mediante un fragmento de anticuerpo para la administración sistémica de genes. |
| US6908963B2 (en) | 2001-10-09 | 2005-06-21 | Nektar Therapeutics Al, Corporation | Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith |
| TWI438010B (zh) | 2002-05-02 | 2014-05-21 | Wyeth Corp | 卡奇黴素(calicheamicin)衍生物-載體共軛物 |
| AU2003223936A1 (en) * | 2002-05-17 | 2003-12-02 | Kobenhavns Universitet | Method for purifying denatured proteins having a desired disulfide bond configuration |
| EP1570267B1 (en) | 2002-12-03 | 2011-10-12 | UCB Pharma, S.A. | Assay for identifying antibody producing cells |
| GB0312481D0 (en) | 2003-05-30 | 2003-07-09 | Celltech R&D Ltd | Antibodies |
| GB0315450D0 (en) * | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| GB0315457D0 (en) | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| CA2527020A1 (en) | 2003-07-01 | 2005-01-13 | Celltech R & D Limited | Modified antibody fab fragments |
| MXPA06014065A (es) | 2004-06-01 | 2007-01-31 | Genentech Inc | Conjugados de droga-anticuerpo y metodos. |
| GB0412181D0 (en) | 2004-06-01 | 2004-06-30 | Celltech R&D Ltd | Biological products |
| US20060051347A1 (en) | 2004-09-09 | 2006-03-09 | Winter Charles M | Process for concentration of antibodies and therapeutic products thereof |
| WO2006047340A2 (en) * | 2004-10-22 | 2006-05-04 | Amgen Inc. | Methods for refolding of recombinant antibodies |
| CA2614082A1 (en) | 2005-07-25 | 2007-02-01 | Trubion Pharmaceuticals, Inc. | Compositions and methods for protein deaggregation |
| US20070212703A1 (en) | 2005-09-27 | 2007-09-13 | Stemmer Willem P | Proteinaceous pharmaceuticals and uses thereof |
| GB0619291D0 (en) | 2006-09-29 | 2006-11-08 | Ucb Sa | Altered antibodies |
| ES2667729T3 (es) | 2007-09-26 | 2018-05-14 | Ucb Biopharma Sprl | Fusiones de anticuerpos con doble especificidad |
| JP5529869B2 (ja) | 2008-08-14 | 2014-06-25 | メルク・シャープ・アンド・ドーム・コーポレーション | プロテインaアフィニティークロマトグラフィーを用いる抗体の精製方法 |
| WO2010035012A1 (en) | 2008-09-26 | 2010-04-01 | Ucb Pharma S.A. | Biological products |
| JP2012503487A (ja) * | 2008-09-26 | 2012-02-09 | シェーリング コーポレイション | 高力価抗体の製造 |
| EP3660032B1 (en) | 2009-06-25 | 2025-10-22 | Amgen Inc. | Capture purification processes for proteins expressed in a non-mammalian system |
| EP2475682B1 (en) | 2009-09-10 | 2018-01-31 | UCB Biopharma SPRL | Multivalent antibodies |
| GB201005063D0 (en) | 2010-03-25 | 2010-05-12 | Ucb Pharma Sa | Biological products |
| GB0920127D0 (en) | 2009-11-17 | 2009-12-30 | Ucb Pharma Sa | Antibodies |
| GB201000467D0 (en) | 2010-01-12 | 2010-02-24 | Ucb Pharma Sa | Antibodies |
| CN102892780B (zh) * | 2010-03-17 | 2015-07-29 | 通益制药有限公司 | 获得生物活性的重组人g-csf的方法 |
| EP2550297B1 (en) | 2010-03-25 | 2019-01-23 | UCB Biopharma SPRL | Disulfide stabilized dvd-lg molecules |
| GB201005064D0 (en) | 2010-03-25 | 2010-05-12 | Ucb Pharma Sa | Biological products |
| CA2812058C (en) * | 2010-09-20 | 2019-04-16 | Bio-Rad Laboratories, Inc. | Dissociation of product-complexed contaminants in chromatography |
| US8759617B2 (en) * | 2010-09-21 | 2014-06-24 | National Institute Of Agrobiological Sciences | Method for extraction and purification of recombinant proteins from transgenic plants |
| AU2012305714A1 (en) * | 2011-09-09 | 2014-03-27 | Biomed Realty, L.P. | Methods and compositions for controlling assembly of viral proteins |
| SG11201401649VA (en) * | 2011-11-11 | 2014-07-30 | Ucb Pharma Sa | Albumin binding antibodies and binding fragments thereof |
| UA112203C2 (uk) | 2011-11-11 | 2016-08-10 | Юсб Фарма С.А. | Злитий білок біоспецифічного антитіла, який зв'язується з ox40 людини та сироватковим альбуміном людини |
| US20160060291A1 (en) * | 2012-03-30 | 2016-03-03 | Biogenomics Limited | Process for renaturation of polypeptides |
| GB201208370D0 (en) | 2012-05-14 | 2012-06-27 | Ucb Pharma Sa | Antibodies |
| PL2922872T3 (pl) | 2012-11-21 | 2019-03-29 | Janssen Biotech, Inc. | Bispecyficzne przeciwciała przeciwko egfr/c-met |
| CN106133137A (zh) | 2014-03-07 | 2016-11-16 | 生物纳米基因公司 | 多核苷酸的处理 |
| GB201411320D0 (en) | 2014-06-25 | 2014-08-06 | Ucb Biopharma Sprl | Antibody construct |
| GB201506869D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method |
| GB201506868D0 (en) | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method for protein purification |
| GB201506870D0 (en) * | 2015-04-22 | 2015-06-03 | Ucb Biopharma Sprl | Method |
| EP3485280A1 (en) | 2016-08-12 | 2019-05-22 | Lonza Ltd | Proteomic analysis of host cell proteins |
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2016
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| CN108064230A (zh) | 2018-05-22 |
| JP6898251B2 (ja) | 2021-07-07 |
| JP2018515449A (ja) | 2018-06-14 |
| CA2981644C (en) | 2023-07-04 |
| GB201506870D0 (en) | 2015-06-03 |
| SG11201708151TA (en) | 2017-11-29 |
| EP3286204A1 (en) | 2018-02-28 |
| WO2016170138A1 (en) | 2016-10-27 |
| US11786593B2 (en) | 2023-10-17 |
| MX2017013376A (es) | 2017-12-07 |
| EA201792329A1 (ru) | 2018-02-28 |
| CL2017002676A1 (es) | 2018-03-23 |
| US20180117153A1 (en) | 2018-05-03 |
| CO2017010385A2 (es) | 2018-03-20 |
| BR112017021812A2 (pt) | 2018-07-10 |
| US10828366B2 (en) | 2020-11-10 |
| AU2016251620A1 (en) | 2017-10-26 |
| CN108064230B (zh) | 2021-04-06 |
| EP3286204B1 (en) | 2020-11-18 |
| CA2981644A1 (en) | 2016-10-27 |
| KR20170138552A (ko) | 2017-12-15 |
| IL254765A0 (en) | 2017-12-31 |
| US20210069328A1 (en) | 2021-03-11 |
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