EA202091422A1 - Способ непрерывного производства продуктов на основе биспецифических антител - Google Patents

Способ непрерывного производства продуктов на основе биспецифических антител

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Publication number
EA202091422A1
EA202091422A1 EA202091422A EA202091422A EA202091422A1 EA 202091422 A1 EA202091422 A1 EA 202091422A1 EA 202091422 A EA202091422 A EA 202091422A EA 202091422 A EA202091422 A EA 202091422A EA 202091422 A1 EA202091422 A1 EA 202091422A1
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Eurasian Patent Office
Prior art keywords
bispecific antibody
continuous production
perfusion
bispecific antibodies
products based
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EA202091422A
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English (en)
Inventor
Четан Гоудар
Роухини Дешпенд
Наталия Гомес
Хедье Бархордарьян
Янь Ван
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Эмджен Инк.
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Publication of EA202091422A1 publication Critical patent/EA202091422A1/ru

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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
    • 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
    • C07K16/2809—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 the T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • 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
    • 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
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • C07K16/2875—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/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • 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
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
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    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/10—Perfusion
    • C—CHEMISTRY; METALLURGY
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018—Culture media for cell or tissue culture
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/44—Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/24—Stationary reactors without moving elements inside
    • B01J2219/2401—Reactors comprising multiple separate flow channels
    • B01J2219/2402—Monolithic-type reactors
    • B01J2219/2441—Other constructional details
    • B01J2219/2444—Size aspects
    • B01J2219/2446—Cell density
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/24—Stationary reactors without moving elements inside
    • B01J2219/2401—Reactors comprising multiple separate flow channels
    • B01J2219/245—Plate-type reactors
    • B01J2219/2461—Heat exchange aspects
    • B01J2219/2466—The same reactant stream undergoing different reactions, endothermic or exothermic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
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    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
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  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

В настоящем изобретении предусмотрен способ непрерывного производства на этапе накопления для получения продуктов на основе биспецифических антител, содержащих по меньшей мере два связывающих домена. Способ включает, по меньшей мере, стадии (i) обеспечения в перфузионном биореакторе по меньшей мере одной культуры клеток млекопитающих, которая способна экспрессировать продукт на основе биспецифического антитела, (ii) выращивания культуры клеток млекопитающих при первой скорости перфузии до момента достижения заданного значения плотности жизнеспособных клеток и (iii) поддержания перфузионной культуры при второй скорости перфузии, где концентрацию продукта на основе биспецифического антитела в биореакторе поддерживают ниже порогового значения. Затем продукт на основе биспецифического антитела подвергают последующей обработке на этапе выделения и очистки. Более того, в настоящем изобретении предусмотрен продукт на основе биспецифического антитела, полученный с помощью способа непрерывного производства на этапе накопления.
EA202091422A 2017-12-11 2018-12-11 Способ непрерывного производства продуктов на основе биспецифических антител EA202091422A1 (ru)

Applications Claiming Priority (2)

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US201762597250P 2017-12-11 2017-12-11
PCT/US2018/064901 WO2019118426A1 (en) 2017-12-11 2018-12-11 Continuous manufacturing process for bispecific antibody products

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EA202091422A1 true EA202091422A1 (ru) 2020-08-28

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US (1) US20210163592A1 (ru)
EP (1) EP3724229A1 (ru)
JP (1) JP7344206B2 (ru)
KR (1) KR20200096814A (ru)
CN (1) CN111315780A (ru)
AR (1) AR113491A1 (ru)
AU (1) AU2018383679A1 (ru)
BR (1) BR112020011627A2 (ru)
CA (1) CA3082507A1 (ru)
CL (1) CL2020001536A1 (ru)
EA (1) EA202091422A1 (ru)
IL (1) IL275054A (ru)
MX (1) MX2020006007A (ru)
SG (1) SG11202004273YA (ru)
TW (1) TWI827570B (ru)
WO (1) WO2019118426A1 (ru)
ZA (1) ZA202003424B (ru)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JO3519B1 (ar) * 2013-01-25 2020-07-05 Amgen Inc تركيبات أجسام مضادة لأجل cdh19 و cd3
EA202190955A1 (ru) * 2018-10-01 2021-08-17 Эмджен Инк. Способы снижения агрегации биспецифических антител
TW202043253A (zh) 2019-01-28 2020-12-01 美商安進公司 藉由將藥物物質和藥物產品過程整體化的生物製劑製造之連續製造過程
TWI793503B (zh) * 2020-01-20 2023-02-21 美商美國禮來大藥廠 抗IL-1β抗體
CN114438034A (zh) * 2020-11-06 2022-05-06 上海赛比曼生物科技有限公司 一种基因修饰的细胞制备方法
AU2022212007A1 (en) * 2021-01-29 2023-09-07 Merck Sharp & Dohme Llc Compositions of programmed death receptor 1 (pd-1) antibodies and methods of obtaining the compositions thereof
EP4330281A1 (en) * 2021-04-29 2024-03-06 Amgen Inc. Methods for reducing low molecular weight species of recombinantly-produced proteins

Family Cites Families (141)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3180193A (en) 1963-02-25 1965-04-27 Benedict David Machines for cutting lengths of strip material
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US3691016A (en) 1970-04-17 1972-09-12 Monsanto Co Process for the preparation of insoluble enzymes
CA1023287A (en) 1972-12-08 1977-12-27 Boehringer Mannheim G.M.B.H. Process for the preparation of carrier-bound proteins
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US4195128A (en) 1976-05-03 1980-03-25 Bayer Aktiengesellschaft Polymeric carrier bound ligands
US4330440A (en) 1977-02-08 1982-05-18 Development Finance Corporation Of New Zealand Activated matrix and method of activation
CA1093991A (en) 1977-02-17 1981-01-20 Hideo Hirohara Enzyme immobilization with pullulan gel
US4229537A (en) 1978-02-09 1980-10-21 New York University Preparation of trichloro-s-triazine activated supports for coupling ligands
US4263428A (en) 1978-03-24 1981-04-21 The Regents Of The University Of California Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same
JPS6023084B2 (ja) 1979-07-11 1985-06-05 味の素株式会社 代用血液
IE52535B1 (en) 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
US4640835A (en) 1981-10-30 1987-02-03 Nippon Chemiphar Company, Ltd. Plasminogen activator derivatives
DE3374837D1 (en) 1982-02-17 1988-01-21 Ciba Geigy Ag Lipids in the aqueous phase
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
HUT35524A (en) 1983-08-02 1985-07-29 Hoechst Ag Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance
EP0143949B1 (en) 1983-11-01 1988-10-12 TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION Pharmaceutical composition containing urokinase
US4496689A (en) 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4694778A (en) 1984-05-04 1987-09-22 Anicon, Inc. Chemical vapor deposition wafer boat
JPS6147500A (ja) 1984-08-15 1986-03-07 Res Dev Corp Of Japan キメラモノクロ−ナル抗体及びその製造法
EP0173494A3 (en) 1984-08-27 1987-11-25 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by dna splicing and expression
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
US4879231A (en) 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4751180A (en) 1985-03-28 1988-06-14 Chiron Corporation Expression using fused genes providing for protein product
DE3675588D1 (de) 1985-06-19 1990-12-20 Ajinomoto Kk Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist.
US4935233A (en) 1985-12-02 1990-06-19 G. D. Searle And Company Covalently linked polypeptide cell modulators
EP0272253A4 (en) 1986-03-07 1990-02-05 Massachusetts Inst Technology METHOD FOR IMPROVING GLYCOPROTE INSTABILITY.
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
GB8610600D0 (en) 1986-04-30 1986-06-04 Novo Industri As Transformation of trichoderma
US4791192A (en) 1986-06-26 1988-12-13 Takeda Chemical Industries, Ltd. Chemically modified protein with polyethyleneglycol
ATE87659T1 (de) 1986-09-02 1993-04-15 Enzon Lab Inc Bindungsmolekuele mit einzelpolypeptidkette.
US5260203A (en) 1986-09-02 1993-11-09 Enzon, Inc. Single polypeptide chain binding molecules
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
WO1988007089A1 (en) 1987-03-18 1988-09-22 Medical Research Council Altered antibodies
ATE243754T1 (de) 1987-05-21 2003-07-15 Micromet Ag Multifunktionelle proteine mit vorbestimmter zielsetzung
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US5476996A (en) 1988-06-14 1995-12-19 Lidak Pharmaceuticals Human immune system in non-human animal
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
US5175384A (en) 1988-12-05 1992-12-29 Genpharm International Transgenic mice depleted in mature t-cells and methods for making transgenic mice
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
EP0402226A1 (en) 1989-06-06 1990-12-12 Institut National De La Recherche Agronomique Transformation vectors for yeast yarrowia
US5683888A (en) 1989-07-22 1997-11-04 University Of Wales College Of Medicine Modified bioluminescent proteins and their use
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5859205A (en) 1989-12-21 1999-01-12 Celltech Limited Humanised antibodies
US5292658A (en) 1989-12-29 1994-03-08 University Of Georgia Research Foundation, Inc. Boyd Graduate Studies Research Center Cloning and expressions of Renilla luciferase
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
EP1690935A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for 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
DK0546073T3 (da) 1990-08-29 1998-02-02 Genpharm Int Frembringelse og anvendelse af transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
WO1993012227A1 (en) 1991-12-17 1993-06-24 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
CA2090473A1 (en) 1990-08-29 1992-03-01 Robert M. Kay Homologous recombinatin in mammalian cells
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
JP3126980B2 (ja) 1991-03-11 2001-01-22 ザ・ユニバーシテイ・オブ・ジヨージア・リサーチ・フアウンデーシヨン・インコーポレーテツド レニラ（ｒｅｎｉｌｌａ）ルシフェラーゼのクローニング及び発現
WO1992022670A1 (en) 1991-06-12 1992-12-23 Genpharm International, Inc. Early detection of transgenic embryos
DK0590058T3 (da) 1991-06-14 2004-03-29 Genentech Inc Humaniseret heregulin-antistof
WO1992022645A1 (en) 1991-06-14 1992-12-23 Genpharm International, Inc. Transgenic immunodeficient non-human animals
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
US5565332A (en) 1991-09-23 1996-10-15 Medical Research Council Production of chimeric antibodies - a combinatorial approach
NZ253943A (en) 1992-06-18 1997-01-29 Genpharm Int Transfering polynucleotides into eukaryotic cells using co-lipofection complexes of a cationic lipid and the polynucleotide
WO1994002602A1 (en) 1992-07-24 1994-02-03 Cell Genesys, Inc. Generation of xenogeneic antibodies
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
US5981175A (en) 1993-01-07 1999-11-09 Genpharm Internation, Inc. Methods for producing recombinant mammalian cells harboring a yeast artificial chromosome
AU6819494A (en) 1993-04-26 1994-11-21 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
KR960705209A (ko) 1993-09-10 1996-10-09 잭 엠. 그랜노위츠 녹색 형광 단백의 용도
US5625825A (en) 1993-10-21 1997-04-29 Lsi Logic Corporation Random number generating apparatus for an interface unit of a carrier sense with multiple access and collision detect (CSMA/CD) ethernet data network
WO1995021191A1 (en) 1994-02-04 1995-08-10 William Ward Bioluminescent indicator based upon the expression of a gene for a modified green-fluorescent protein
US5643763A (en) 1994-11-04 1997-07-01 Genpharm International, Inc. Method for making recombinant yeast artificial chromosomes by minimizing diploid doubling during mating
US6214388B1 (en) 1994-11-09 2001-04-10 The Regents Of The University Of California Immunoliposomes that optimize internalization into target cells
US5777079A (en) 1994-11-10 1998-07-07 The Regents Of The University Of California Modified green fluorescent proteins
DE69637481T2 (de) 1995-04-27 2009-04-09 Amgen Fremont Inc. Aus immunisierten Xenomäusen stammende menschliche Antikörper gegen IL-8
AU2466895A (en) 1995-04-28 1996-11-18 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5811524A (en) 1995-06-07 1998-09-22 Idec Pharmaceuticals Corporation Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof
AU725609C (en) 1995-08-18 2002-01-03 Morphosys Ag Protein/(poly)peptide libraries
CA2230759C (en) 1995-08-29 2012-02-21 Kirin Beer Kabushiki Kaisha Chimeric animal and method for producing the same
US5874304A (en) 1996-01-18 1999-02-23 University Of Florida Research Foundation, Inc. Humanized green fluorescent protein genes and methods
US5804387A (en) 1996-02-01 1998-09-08 The Board Of Trustees Of The Leland Stanford Junior University FACS-optimized mutants of the green fluorescent protein (GFP)
US5876995A (en) 1996-02-06 1999-03-02 Bryan; Bruce Bioluminescent novelty items
US5925558A (en) 1996-07-16 1999-07-20 The Regents Of The University Of California Assays for protein kinases using fluorescent protein substrates
US5976796A (en) 1996-10-04 1999-11-02 Loma Linda University Construction and expression of renilla luciferase and green fluorescent protein fusion genes
ATE387495T1 (de) 1996-12-03 2008-03-15 Amgen Fremont Inc Vollkommen humane antikörper die egfr binden
US6458547B1 (en) 1996-12-12 2002-10-01 Prolume, Ltd. Apparatus and method for detecting and identifying infectious agents
CA2290485C (en) 1997-05-21 2008-08-05 Biovation Limited Method for the production of non-immunogenic proteins
DE69938293T2 (de) 1998-03-27 2009-03-12 Bruce J. Beverly Hills Bryan Luciferase, gfp fluoreszenzproteine, kodierende nukleinsaüre und ihre verwendung in der diagnose
KR100508289B1 (ko) 1998-04-21 2005-08-17 마이크로메트 에이지 Ｃｄ１９×ｃｄ３ 특이 폴리펩티드 및 그의 용도
AU5728999A (en) 1998-07-28 2000-02-21 Micromet Ag Heterominibodies
ES2278463T3 (es) 1998-12-08 2007-08-01 Biovation Limited Metodo para reducir la inmunogenicidad de proteinas.
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US7435871B2 (en) 2001-11-30 2008-10-14 Amgen Fremont Inc. Transgenic animals bearing human Igλ light chain genes
ATE493441T1 (de) 2003-10-16 2011-01-15 Micromet Ag Multispezifische deimmunisierte cd3-bindende moleküle
CN1930281A (zh) * 2004-03-05 2007-03-14 帝斯曼知识产权资产管理有限公司 用于通过连续灌注和交互切向流来培养细胞的方法
EP1909831A4 (en) 2005-06-14 2013-02-20 Amgen Inc PREPARATIONS OF SPONTANEOUS TAMPING PROTEINS
EP3770174A1 (en) 2005-10-11 2021-01-27 Amgen Research (Munich) GmbH Compositions comprising cross-species-specific antibodies and uses thereof
US8119368B2 (en) * 2006-07-14 2012-02-21 Dsm Ip Assets B.V. Process for the culturing of cells
WO2008036600A2 (en) * 2006-09-18 2008-03-27 Genentech, Inc. Methods of protein production
US7466008B2 (en) 2007-03-13 2008-12-16 Taiwan Semiconductor Manufacturing Company, Ltd. BiCMOS performance enhancement by mechanical uniaxial strain and methods of manufacture
SI2155783T1 (sl) 2007-04-03 2013-10-30 Amgen Research (Munich) Gmbh Medvrstno specifiäśna cd3-epsilon vezavna domena
WO2010037838A2 (en) 2008-10-01 2010-04-08 Micromet Ag Cross-species-specific single domain bispecific single chain antibody
JP5770633B2 (ja) * 2008-11-03 2015-08-26 クルセル ホランド ベー ヴェー アデノウイルスベクターの産生方法
HUE028175T2 (en) * 2008-11-07 2016-12-28 Amgen Res (Munich) Gmbh Treatment of acute lymphoblastic leukemia
US20130078250A1 (en) 2011-08-23 2013-03-28 Oliver Ast Bispecific t cell activating antigen binding molecules
ES2857734T3 (es) 2011-08-23 2021-09-29 Roche Glycart Ag Moléculas de unión a antígeno activadoras de linfocitos T biespecíficas
US9041762B2 (en) 2011-09-26 2015-05-26 Prysm, Inc. 2-D straight-scan on imaging surface with a raster polygon
US20140308285A1 (en) 2013-03-15 2014-10-16 Amgen Inc. Heterodimeric bispecific antibodies
US20140302037A1 (en) 2013-03-15 2014-10-09 Amgen Inc. BISPECIFIC-Fc MOLECULES
EP2970484B2 (en) 2013-03-15 2022-09-21 Amgen Inc. Heterodimeric bispecific antibodies
WO2015048272A1 (en) 2013-09-25 2015-04-02 Amgen Inc. V-c-fc-v-c antibody
WO2015095809A1 (en) * 2013-12-20 2015-06-25 Biogen Idec Ma Inc. Use of perfusion seed cultures to improve biopharmaceutical fed-batch production capacity and product quality
US9300829B2 (en) 2014-04-04 2016-03-29 Canon Kabushiki Kaisha Image reading apparatus and correction method thereof
RU2577226C2 (ru) * 2014-04-10 2016-03-10 Общество с ограниченной ответственностью, "Международный биотехнологический центр "Генериум" ("МБЦ "Генериум") Способ получения биспецифических антител против cd3*cd19 формата флексибоди в клетках млекопитающих
JP6749312B2 (ja) * 2014-07-31 2020-09-02 アムゲン リサーチ （ミュンヘン） ゲーエムベーハーＡＭＧＥＮ Ｒｅｓｅａｒｃｈ（Ｍｕｎｉｃｈ）ＧｍｂＨ 最適化された種間特異的二重特異性単鎖抗体コンストラクト
US10105142B2 (en) 2014-09-18 2018-10-23 Ethicon Llc Surgical stapler with plurality of cutting elements
CA3001761A1 (en) * 2015-10-26 2017-05-04 Lonza Limited A manufacturing facility for the production of biopharmaceuticals
US20170204446A1 (en) * 2016-01-15 2017-07-20 Artemis BioSystems Inc. System for rapid continuous manufacturing of monoclonal antibodies
EA039859B1 (ru) 2016-02-03 2022-03-21 Эмджен Рисерч (Мюник) Гмбх Биспецифические конструкты антител, связывающие egfrviii и cd3
KR20200064131A (ko) * 2017-10-13 2020-06-05 베링거 인겔하임 인터내셔날 게엠베하 관류 배지

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