CL2020001536A1 - Procedimiento de fabricación continuo para productos de anticuerpos biespecíficos. - Google Patents

Procedimiento de fabricación continuo para productos de anticuerpos biespecíficos.

Info

Publication number
CL2020001536A1
CL2020001536A1 CL2020001536A CL2020001536A CL2020001536A1 CL 2020001536 A1 CL2020001536 A1 CL 2020001536A1 CL 2020001536 A CL2020001536 A CL 2020001536A CL 2020001536 A CL2020001536 A CL 2020001536A CL 2020001536 A1 CL2020001536 A1 CL 2020001536A1
Authority
CL
Chile
Prior art keywords
bispecific antibody
perfusion
antibody product
continuous manufacturing
manufacturing procedure
Prior art date
Application number
CL2020001536A
Other languages
English (en)
Inventor
Hedieh Barkhordarian
Chetan Goudar
Rohini Deshpande
Natalia Gomez
Yan Wang
Original Assignee
Amgen Inc
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
Application filed by Amgen Inc filed Critical Amgen Inc
Publication of CL2020001536A1 publication Critical patent/CL2020001536A1/es

Links

Classifications

    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [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
    • C07K16/2809Immunoglobulins [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
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [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
    • 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
    • C07K16/24Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241Tumor Necrosis Factors
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863Immunoglobulins [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
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875Immunoglobulins [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
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878Immunoglobulins [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
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3069Reproductive system, e.g. ovaria, uterus, testes, prostate
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/10Perfusion
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018Culture media for cell or tissue culture
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/44Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00725Peptides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/24Stationary reactors without moving elements inside
    • B01J2219/2401Reactors comprising multiple separate flow channels
    • B01J2219/2402Monolithic-type reactors
    • B01J2219/2441Other constructional details
    • B01J2219/2444Size aspects
    • B01J2219/2446Cell density
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/24Stationary reactors without moving elements inside
    • B01J2219/2401Reactors comprising multiple separate flow channels
    • B01J2219/245Plate-type reactors
    • B01J2219/2461Heat exchange aspects
    • B01J2219/2466The same reactant stream undergoing different reactions, endothermic or exothermic
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/10Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14Specific host cells or culture conditions, e.g. components, pH or temperature
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00Tissue, human, animal or plant cell, or virus culture apparatus
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2521/00Culture process characterised by the use of hydrostatic pressure, flow or shear forces

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Sustainable Development (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La presente invención proporciona un procedimiento de fabricación anterior continuo para la producción de productos de anticuerpos biespecíficos, que comprenden al menos dos dominios de unión. El procedimiento comprende al menos las etapas de (i) proporcionar en un biorreactor de perfusión al menos un cultivo celular de mamífero, que es capaz de expresar el producto de anticuerpos biespecíficos, (ii) hacer crecer el cultivo celular de mamífero a una primera tasa de perfusión hasta que se alcanza un punto de ajuste de densidad celular viable y (iii) mantener el cultivo de perfusión a una segunda tasa de perfusión, en el que la concentración de producto de anticuerpos biespecíficos en el biorreactor se mantiene por debajo de un valor umbral. El producto de anticuerpos biespecíficos se somete luego a un procesamiento aguas abajo posterior. Además, la invención proporciona un producto de anticuerpos biespecíficos producido mediante el procedimiento de fabricación anterior continuo.
CL2020001536A 2017-12-11 2020-06-09 Procedimiento de fabricación continuo para productos de anticuerpos biespecíficos. CL2020001536A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201762597250P 2017-12-11 2017-12-11

Publications (1)

Publication Number Publication Date
CL2020001536A1 true CL2020001536A1 (es) 2020-09-04

Family

ID=65201664

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2020001536A CL2020001536A1 (es) 2017-12-11 2020-06-09 Procedimiento de fabricación continuo para productos de anticuerpos biespecíficos.

Country Status (17)

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

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
CA3112655A1 (en) * 2018-10-01 2020-04-09 Amgen Inc. Methods for reducing aggregation of bispecific antibodies
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
JP2024505524A (ja) * 2021-01-29 2024-02-06 メルク・シャープ・アンド・ドーム・エルエルシー プログラム死受容体1(pd-1)抗体の組成物及びその組成物を得る方法
WO2022232376A1 (en) * 2021-04-29 2022-11-03 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
EP0088046B1 (de) 1982-02-17 1987-12-09 Ciba-Geigy Ag Lipide in wässriger 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
JPS63502716A (ja) 1986-03-07 1988-10-13 マサチューセッツ・インステチュート・オブ・テクノロジー 糖タンパク安定性の強化方法
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
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
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
WO1988001649A1 (en) 1986-09-02 1988-03-10 Genex Corporation Single polypeptide chain binding molecules
US5260203A (en) 1986-09-02 1993-11-09 Enzon, Inc. Single polypeptide chain binding molecules
DE3883899T3 (de) 1987-03-18 1999-04-22 Sb2, Inc., Danville, Calif. Geänderte antikörper.
DE3856559T2 (de) 1987-05-21 2004-04-29 Micromet Ag Multifunktionelle Proteine mit vorbestimmter Zielsetzung
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
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
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
DE69133566T2 (de) 1990-01-12 2007-12-06 Amgen Fremont Inc. Bildung von xenogenen Antikörpern
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
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
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5814318A (en) 1990-08-29 1998-09-29 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
EP0814159B1 (en) 1990-08-29 2005-07-27 GenPharm International, Inc. Transgenic mice capable of producing heterologous antibodies
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
EP0546091B1 (en) 1990-08-29 2007-01-24 Pharming Intellectual Property BV Homologous recombination in mammalian cells
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
WO1994025585A1 (en) 1993-04-26 1994-11-10 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
ES2142801T3 (es) 1991-03-11 2000-05-01 Univ Georgia Res Found Clonacion y expresion de luciferasa de renilla.
WO1992022670A1 (en) 1991-06-12 1992-12-23 Genpharm International, Inc. Early detection of transgenic embryos
WO1992022645A1 (en) 1991-06-14 1992-12-23 Genpharm International, Inc. Transgenic immunodeficient non-human animals
AU675916B2 (en) 1991-06-14 1997-02-27 Genentech Inc. Method for making humanized antibodies
AU2515992A (en) 1991-08-20 1993-03-16 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
ES2136092T3 (es) 1991-09-23 1999-11-16 Medical Res Council Procedimientos para la produccion de anticuerpos humanizados.
CA2124967C (en) 1991-12-17 2008-04-08 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
JPH07508410A (ja) 1992-06-18 1995-09-21 ジェンファーム インターナショナル インコーポレイテッド 酵母人工染色体を有するトランスジェニック非ヒト動物の製造方法
EP0652950B1 (en) 1992-07-24 2007-12-19 Amgen Fremont 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
EP0759170B1 (en) 1993-09-10 2008-07-09 The Trustees Of Columbia University In The City Of New York Uses of green fluorescent protein
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
ATE390933T1 (de) 1995-04-27 2008-04-15 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
CA2229043C (en) 1995-08-18 2016-06-07 Morphosys Gesellschaft Fur Proteinoptimierung Mbh Protein/(poly)peptide libraries
EP0843961B1 (en) 1995-08-29 2007-01-24 Kirin Beer Kabushiki Kaisha Chimeric animal and method for constructing 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
AU5702298A (en) 1996-12-03 1998-06-29 Abgenix, Inc. Transgenic mammals having human Ig loci including plural VH and VK regions nd antibodies produced therefrom
US6458547B1 (en) 1996-12-12 2002-10-01 Prolume, Ltd. Apparatus and method for detecting and identifying infectious agents
DE69833755T2 (de) 1997-05-21 2006-12-28 Biovation Ltd. Verfahren zur herstellung von nicht-immunogenen proteinen
AU765703B2 (en) 1998-03-27 2003-09-25 Bruce J. Bryan Luciferases, fluorescent proteins, nucleic acids encoding the luciferases and fluorescent proteins and the use thereof in diagnostics, high throughput screening and novelty items
DE69909459T2 (de) 1998-04-21 2004-05-27 Micromet Ag Cd19xcd3 spezifische polypeptide und deren verwendung
WO2000006605A2 (en) 1998-07-28 2000-02-10 Micromet Ag Heterominibodies
CN1202128C (zh) 1998-12-08 2005-05-18 拜奥威神有限公司 修饰蛋白的免疫原性
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
CA2847885C (en) 2001-11-30 2022-03-22 Amgen Fremont Inc. Transgenic animals bearing human ig.lambda. light chain genes
KR101229731B1 (ko) 2003-10-16 2013-03-07 암젠 리서치 (뮌헨) 게엠베하 다중특이적 탈면역화된 cd3-바인더
JP2007525984A (ja) * 2004-03-05 2007-09-13 ディーエスエム アイピー アセッツ ビー.ブイ. 連続的灌流および交互接線流による細胞培養の方法
KR20080031684A (ko) 2005-06-14 2008-04-10 암젠 인코포레이티드 자가 - 완충성 단백질 제형
EP1940881B1 (en) 2005-10-11 2016-11-30 Amgen Research (Munich) GmbH Compositions comprising cross-species-specific antibodies and uses thereof
SI2041259T1 (sl) * 2006-07-14 2016-04-29 Dpx Holdings B.V. Izboljšan postopek kultiviranja celic
US10982250B2 (en) * 2006-09-18 2021-04-20 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
ES2432792T5 (es) 2007-04-03 2023-01-16 Amgen Res Munich Gmbh Dominio de unión a CD3-épsilon específico de especies cruzadas
AU2009299794B2 (en) 2008-10-01 2015-08-13 Amgen Research (Munich) Gmbh Cross-species-specific single domain bispecific single chain antibody
PL2350268T3 (pl) * 2008-11-03 2015-05-29 Crucell Holland Bv Sposób wytwarzania wektorów adenowirusowych
WO2010052014A1 (en) * 2008-11-07 2010-05-14 Micromet Ag Treatment of acute lymphoblastic leukemia
WO2013026837A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
PE20141521A1 (es) 2011-08-23 2014-10-25 Roche Glycart Ag Moleculas biespecificas de union a antigeno activadoras de celulas t
US9041762B2 (en) 2011-09-26 2015-05-26 Prysm, Inc. 2-D straight-scan on imaging surface with a raster polygon
AU2014236769B2 (en) 2013-03-15 2018-09-27 Amgen Inc. Heterodimeric bispecific antibodies
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
US20160257748A1 (en) 2013-09-25 2016-09-08 Amgen Inc. V-c-fc-v-c antibody
EP3083933A1 (en) * 2013-12-20 2016-10-26 Biogen 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
US11008540B2 (en) * 2015-10-26 2021-05-18 Lonza Ltd. 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
EP3673045B1 (en) * 2017-10-13 2024-01-17 Boehringer Ingelheim International GmbH Perfusion medium

Also Published As

Publication number Publication date
AU2018383679A1 (en) 2020-05-07
IL275054A (en) 2020-07-30
US20210163592A1 (en) 2021-06-03
BR112020011627A2 (pt) 2020-11-17
TWI827570B (zh) 2024-01-01
TW201938586A (zh) 2019-10-01
KR20200096814A (ko) 2020-08-13
EA202091422A1 (ru) 2020-08-28
MX2020006007A (es) 2020-08-17
SG11202004273YA (en) 2020-06-29
CA3082507A1 (en) 2019-06-20
CN111315780A (zh) 2020-06-19
EP3724229A1 (en) 2020-10-21
ZA202003424B (en) 2024-04-24
JP2021505182A (ja) 2021-02-18
AR113491A1 (es) 2020-05-06
JP7344206B2 (ja) 2023-09-13
WO2019118426A1 (en) 2019-06-20

Similar Documents

Publication Publication Date Title
CL2020001536A1 (es) Procedimiento de fabricación continuo para productos de anticuerpos biespecíficos.
AR080434A1 (es) Metodo para purificar celulas derivadas de celulas madre pluripotenciales
PH12017501089A1 (en) Methods of producing long acting ctp-modified growth hormone polypeptides
MX2020003555A (es) Sistemas de espectroscopia raman in situ y metodos para controlar variables de proceso en cultivos celulares.
SG10201902355VA (en) Ultra-high density cell banking methods
BR112018075548A2 (pt) método para estabilizar proteínas
MX2018004580A (es) Metodo para producir proteina de fusion con dominio fc de igg.
PH12016502406A1 (en) Cell culture process for producing a protein
AU2016237923A8 (en) Method of maintaining ovaries of marine fish, method of adjusting culture solution, and method of producing eggs or fertilized eggs of marine fish
SG11201806843UA (en) Method for producing activated hepatocyte growth factor (hgf)
BR112016009619A2 (pt) métodos para sacarificar um material celulósico e para produzir um produto de fermentação a partir de material celulósico
AR104050A1 (es) Proceso de producción con iones de cobre controlados
PH12020550798A1 (en) Materials and methods including for sex selection
MX2022000002A (es) Método para cultivo de células adherentes en un biorreactor multiparalelo.
MX2017010421A (es) Metodo para obtener alto rendimiento de clones celulares de expresion estable y moleculas de anticuerpos obtenidas de este modo.
WO2019070435A8 (en) Methods for selectively expanding cells expressing a tcr with a murine constant region
MX2015014207A (es) Metodo de procesamiento de un producto de grano.
AR113449A1 (es) Sistemas y métodos de espectroscopía de raman in situ para controlar variables de procesos en cultivos celulares
MY184625A (en) Methods of producing long acting ctp-modified growth hormone polypeptides
PH12020551280A1 (en) Systems and methods for the preparation of plant derived products using osmosis techniques
MX2015001503A (es) Sistema y proceso de cultivo de celulas sincronizadas en biorreactores.
UA117574U (uk) Спосіб виготовлення лістеріозної сироватки іеквм для реакції зв'язування комплементу (рзк)
MX2021014118A (es) Metodo para expandir celulas madre adultas a partir de sangre total.
AR125455A1 (es) Modulación de la calidad de producto de anticuerpos multiespecíficos asimétricos a través del uso de la temperatura
MX2015017690A (es) Metodo de cultivo de pejelagarto (atractosteus tropicus).