KR20150140679A - 항원-특이적 b 세포를 확인하고 단리시키고, 원하는 항원에 대한 항체를 생성하기 위한 프로토콜 - Google Patents

항원-특이적 b 세포를 확인하고 단리시키고, 원하는 항원에 대한 항체를 생성하기 위한 프로토콜 Download PDF

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KR20150140679A
KR20150140679A KR1020157028403A KR20157028403A KR20150140679A KR 20150140679 A KR20150140679 A KR 20150140679A KR 1020157028403 A KR1020157028403 A KR 1020157028403A KR 20157028403 A KR20157028403 A KR 20157028403A KR 20150140679 A KR20150140679 A KR 20150140679A
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cells
antigen
specific
cell
antibody
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다니엘 에스. 앨리슨
벤자민 에이치. 둣자르
리온 에프. 가르시아-마르티네즈
케이티 앤더슨
에단 더블유. 오잘라
존 에이. 라탐
젠스 빌그렌
앤 엘리자베쓰 카르발호 젠센
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앨더 바이오파마슈티컬즈, 인코포레이티드
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G—PHYSICS
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56972—White blood cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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    • C07—ORGANIC CHEMISTRY
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    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/686—Polymerase chain reaction [PCR]
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    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
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    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/5052—Cells of the immune system involving B-cells
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/534—Production of labelled immunochemicals with radioactive label
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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    • C12Q2561/00—Nucleic acid detection characterised by assay method
    • C12Q2561/113—Real time assay
    • G01N2015/149—

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  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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KR1020157028403A 2013-03-15 2014-03-18 항원-특이적 b 세포를 확인하고 단리시키고, 원하는 항원에 대한 항체를 생성하기 위한 프로토콜 Abandoned KR20150140679A (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361791755P 2013-03-15 2013-03-15
US61/791,755 2013-03-15
PCT/US2014/030994 WO2014146074A2 (en) 2013-03-15 2014-03-18 Protocol for identifying and isolating antigen-specific b cells and producing antibodies to desired antigens

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KR20150140679A true KR20150140679A (ko) 2015-12-16

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KR1020157028403A Abandoned KR20150140679A (ko) 2013-03-15 2014-03-18 항원-특이적 b 세포를 확인하고 단리시키고, 원하는 항원에 대한 항체를 생성하기 위한 프로토콜

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US (2) US20140287952A1 (cg-RX-API-DMAC10.html)
EP (1) EP2972330A4 (cg-RX-API-DMAC10.html)
JP (1) JP6466397B2 (cg-RX-API-DMAC10.html)
KR (1) KR20150140679A (cg-RX-API-DMAC10.html)
AU (1) AU2014232225B2 (cg-RX-API-DMAC10.html)
CA (1) CA2907570A1 (cg-RX-API-DMAC10.html)
IL (1) IL241433B (cg-RX-API-DMAC10.html)
WO (1) WO2014146074A2 (cg-RX-API-DMAC10.html)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
GB201316644D0 (en) 2013-09-19 2013-11-06 Kymab Ltd Expression vector production & High-Throughput cell screening
MX378344B (es) 2014-03-21 2025-03-10 Teva Pharmaceuticals Int Gmbh Anticuerpos antagonistas dirigidos contra el peptido relacionado con el gen de calcitonina y metodos que usan los mismos.
US10556945B2 (en) 2014-03-21 2020-02-11 Teva Pharmaceuticals International Gmbh Antagonist antibodies directed against calcitonin gene-related peptide and methods using same
EP3233916A4 (en) 2014-12-19 2018-06-06 Alder Biopharmaceuticals, Inc. Humanized anti-acth antibodies and use thereof
EP3271393A4 (en) * 2015-03-18 2018-10-31 Epitomics, Inc. High throughput monoclonal antibody generation by b cell panning and proliferation
US20190056398A1 (en) * 2016-02-26 2019-02-21 Sri International Identification and isolation of antibodies from white blood cells
SG10202109691UA (en) 2016-04-15 2021-10-28 Alder Biopharmaceuticals Inc Anti-pacap antibodies and uses thereof
SMT202600087T1 (it) 2016-09-23 2026-03-09 Teva Pharmaceuticals Int Gmbh Trattamento dell’emicrania refrattaria
WO2018102612A1 (en) 2016-12-02 2018-06-07 Juno Therapeutics, Inc. Engineered b cells and related compositions and methods
CN108700576B (zh) * 2017-01-20 2021-07-02 深圳市新产业生物医学工程股份有限公司 制备抗体对的方法、试剂盒及试剂盒的应用和制备抗体对的系统
US11125757B2 (en) * 2017-05-26 2021-09-21 Emory University Methods of culturing and characterizing antibody secreting cells
CN107058235B (zh) * 2017-06-05 2020-08-11 深圳大学 一种b细胞筛选方法及其在单克隆抗体制备中的应用
US20220034902A1 (en) * 2018-12-11 2022-02-03 Merck Sharp & Dohme Corp. Method for identifying high affinity monoclonal antibody heavy and light chain pairs from high throughput screens of b-cell and hybridoma libraries
WO2020242856A1 (en) * 2019-05-31 2020-12-03 The Penn State Research Foundation Specific selection of immune cells using versatile display scaffolds
JP2023519782A (ja) * 2020-01-17 2023-05-15 ジャンプコード ゲノミクス，インク． 標的化された配列決定の方法
CN114441752B (zh) * 2020-11-03 2024-11-26 中国科学院苏州纳米技术与纳米仿生研究所 一种筛选方法
WO2022170074A1 (en) * 2021-02-05 2022-08-11 Amgen Inc. Enhanced hybridoma generation
CN115166241B (zh) * 2022-08-22 2023-03-24 广东忠信生物科技有限公司 一种同时筛选记忆b细胞和浆细胞的高效筛选技术及应用
WO2025240335A1 (en) 2024-05-13 2025-11-20 Regeneron Pharmaceuticals, Inc. Fgfr3 binding molecules and methods of use thereof
WO2026120069A1 (en) 2024-12-05 2026-06-11 H. Lundbeck A/S Humanized anti-pacap antibody and uses thereof

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990000625A1 (en) * 1988-07-14 1990-01-25 Monoclonetics International, Inc. Pre-screening for depletion and enrichment of specific b-cells
CA2090126C (en) 1990-08-02 2002-10-22 John W. Schrader Methods for the production of proteins with a desired function
DE69126281T2 (de) * 1990-11-26 1997-10-16 Akzo Nobel Nv Verfahren zur Herstellung von Antikörpern
US5256542A (en) * 1992-03-09 1993-10-26 Tanox Biosystems, Inc. Selecting low frequency antigen-specific single B lymphocytes with correction for background noise
US5213960A (en) * 1992-03-09 1993-05-25 Tanox Biosystems, Inc. Methods for selecting low frequency antigen-specific single B lymphocytes
US20050287607A1 (en) * 2004-01-07 2005-12-29 Diamond Betty A Methods and compositions for identification of antigen-specific B cell populations
US20060051348A1 (en) * 2004-09-09 2006-03-09 Jorn Gorlach Method of producing a plurality of isolated antibodies to a plurality of cognate antigens
JP2008517914A (ja) * 2004-10-22 2008-05-29 ジェネンコー・インターナショナル・インク ヒトの抗体の分離方法
WO2007046757A1 (en) * 2005-10-17 2007-04-26 Gambro Lundia Ab Extracorporeal blood cleaning
EP2021463B1 (en) * 2006-05-19 2016-11-23 Alder Biopharmaceuticals, Inc. Culture method for obtaining a clonal population of antigen-specific b cells
WO2008073166A2 (en) * 2006-08-23 2008-06-19 Xcellerex, Inc. Multi-variant cell indication technique
NZ578851A (en) * 2007-03-01 2011-09-30 Symphogen As Method for cloning cognate antibodies
EP2238167B1 (en) * 2007-12-27 2015-04-22 Abbott Laboratories Anti-t. cruzi antibodies and methods of use
SI2400298T1 (sl) 2010-05-28 2013-11-29 F. Hoffmann-La Roche Ag Postopek kultivacije posamezne B-celice in izdelava specifičnih protiteles
KR20140043720A (ko) * 2011-03-01 2014-04-10 노보 노르디스크 에이/에스 길항성 ｄｒ3 리간드
WO2013076139A1 (en) * 2011-11-23 2013-05-30 F. Hoffmann-La Roche Ag Cd40l expressing mammalian cells and their use
WO2013130462A1 (en) * 2012-02-29 2013-09-06 Medimmune, Llc Antibody production methods

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JP6466397B2 (ja) 2019-02-06
AU2014232225A1 (en) 2015-09-03
IL241433A0 (en) 2015-11-30
EP2972330A2 (en) 2016-01-20
US20140287952A1 (en) 2014-09-25
EP2972330A4 (en) 2016-10-26
WO2014146074A3 (en) 2014-11-06
IL241433B (en) 2019-12-31
AU2014232225B2 (en) 2020-03-19
JP2016512044A (ja) 2016-04-25
CA2907570A1 (en) 2014-09-18
US20160033504A1 (en) 2016-02-04
WO2014146074A2 (en) 2014-09-18

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