KR102813451B1 - Pac1 항체 및 이의 용도 - Google Patents

Pac1 항체 및 이의 용도 Download PDF

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KR102813451B1
KR102813451B1 KR1020207022600A KR20207022600A KR102813451B1 KR 102813451 B1 KR102813451 B1 KR 102813451B1 KR 1020207022600 A KR1020207022600 A KR 1020207022600A KR 20207022600 A KR20207022600 A KR 20207022600A KR 102813451 B1 KR102813451 B1 KR 102813451B1
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South Korea
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seq
sequence
antibody
antigen
pac1
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KR20200110362A (ko
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니라즈 자그디쉬 아그라왈
어윈 첸
수 총
브리나 푸치스로체르
케빈 그라함
아그네스 에바 함부르
마크 레오 마이클스
크리스토퍼 모어
데렉 이. 파이퍼
케네스 윌리엄 워커
줄룬 왕
센 수
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암젠 인크
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    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • A61P25/00—Drugs for disorders of the nervous system
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    • C07K16/2869—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
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KR1020207022600A 2018-01-12 2019-01-11 Pac1 항체 및 이의 용도 Active KR102813451B1 (ko)

Applications Claiming Priority (3)

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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019140216A1 (en) * 2018-01-12 2019-07-18 Amgen Inc. Pac1 antibodies and uses thereof
EP4087590A4 (en) * 2020-01-12 2024-05-15 Vanderbilt University HUMAN ANTIBODIES AGAINST CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS
CR20220524A (es) * 2020-03-19 2022-12-02 Genentech Inc Anticuerpos anti-tgf-beta con selectividad de isoforma y métodos de uso
IL310329A (en) 2021-07-29 2024-03-01 Cephalon Llc Preparations and methods for anti-PACAP antibodies
AU2023418913A1 (en) * 2022-12-29 2025-06-19 Biyopharma Co., Ltd Fusion protein
CN118039001B (zh) * 2024-02-18 2025-11-25 南开大学 无需精确复合物结构的绝对结合自由能计算方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014144632A2 (en) * 2013-03-15 2014-09-18 Amgen Inc. Human pac1 antibodies

Family Cites Families (104)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US30985A (en) 1860-12-18 Thomas l
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
US4965195A (en) 1987-10-26 1990-10-23 Immunex Corp. Interleukin-7
US4968607A (en) 1987-11-25 1990-11-06 Immunex Corporation Interleukin-1 receptors
DE68925971T2 (de) 1988-09-23 1996-09-05 Cetus Oncology Corp Zellenzuchtmedium für erhöhtes zellenwachstum, zur erhöhung der langlebigkeit und expression der produkte
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
WO1990005183A1 (en) 1988-10-31 1990-05-17 Immunex Corporation Interleukin-4 receptors
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
ES2284161T3 (es) 1990-01-12 2007-11-01 Amgen Fremont Inc. Generacion de anticuerpos xenogenicos.
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
JP3107225B2 (ja) 1990-03-17 2000-11-06 武田薬品工業株式会社 Pacapに対する抗体およびその用途
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
WO1991018982A1 (en) 1990-06-05 1991-12-12 Immunex Corporation Type ii interleukin-1 receptors
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5874299A (en) 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5814318A (en) 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5789650A (en) 1990-08-29 1998-08-04 Genpharm International, Inc. 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
US5877397A (en) 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International 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
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
AU8507191A (en) 1990-08-29 1992-03-30 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
WO1992022646A1 (en) 1991-06-14 1992-12-23 Dnx Corp. Production of human hemoglobin in transgenic pigs
AU3328493A (en) 1991-12-17 1993-07-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ES2301158T3 (es) 1992-07-24 2008-06-16 Amgen Fremont Inc. Produccion de anticuerpos xenogenicos.
EP0618291A3 (en) 1993-02-26 1997-12-03 Takeda Chemical Industries, Ltd. PACAP receptor protein, method for preparing said protein, and use thereof
US6399316B1 (en) 1994-02-25 2002-06-04 Takeda Chemical Industries, Ltd. PACAP receptor protein, method for preparing said protein, and use thereof
US6130364A (en) 1995-03-29 2000-10-10 Abgenix, Inc. Production of antibodies using Cre-mediated site-specific recombination
US6096871A (en) 1995-04-14 2000-08-01 Genentech, Inc. Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life
EP0822830B1 (en) 1995-04-27 2008-04-02 Amgen Fremont Inc. Human anti-IL-8 antibodies, derived from immunized xenomice
US6462016B1 (en) 1995-10-06 2002-10-08 Shiseido Company, Ltd. Method for screening agonist or antagonist of the maxadilan receptor participating in vasodilating action, and compound found by the method
ATE279947T1 (de) 1996-03-18 2004-11-15 Univ Texas Immunglobulinähnliche domäne mit erhöhten halbwertszeiten
US6017533A (en) 1996-04-25 2000-01-25 Shiseido Company, Ltd. Peptides having specific affinity to pituitary adenylate cyclase activating polypeptide type 1 receptors
ATE549918T1 (de) 1996-12-03 2012-04-15 Amgen Fremont Inc Menschliche antikörper, die ausdrücklich menschliches tnf alpha binden
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
PL345583A1 (en) 1998-07-20 2001-12-17 Sod Conseils Rech Applic Peptide analogues of pacap
US6242563B1 (en) 1998-07-20 2001-06-05 Societe De Conseils De Recherches Et D'applications Scientifiques, Sas Peptide analogues
US20020155533A1 (en) 1998-11-30 2002-10-24 Takeda Chemical PACAP receptor protein, method for preparing said protein, and use thereof
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US20020182729A1 (en) 2001-01-11 2002-12-05 Dicicco-Bloom Emanuel Pituitary adenylate cyclase-activating polypeptide (PACAP) is an anti-mitogenic signal for selected neuronal precursors in vivo
AU2002324556A1 (en) 2001-07-25 2003-02-17 Protein Design Labs, Inc. Stable lyophilized pharmaceutical formulation of igg antibodies
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US7220862B2 (en) 2002-06-05 2007-05-22 Bristol-Myers Squibb Company Calcitonin gene related peptide receptor antagonists
US7842808B2 (en) 2002-06-05 2010-11-30 Bristol-Myers Squibb Company Anti-migraine spirocycles
EP1583550A2 (en) 2003-01-16 2005-10-12 D. Collen Research Foundation vzw Inhibition of pacap signalling for the prevention and treatment of thrombocytopenia
US20050129687A1 (en) 2003-11-03 2005-06-16 University Of Vermont And State Agricultural College Use of inhibitors of PACAP receptor activity for treatment of overactive bladder and pelvic floor pain syndrome
EP1701979A2 (en) 2003-12-03 2006-09-20 Xencor, Inc. Optimized antibodies that target the epidermal growth factor receptor
US7569578B2 (en) 2003-12-05 2009-08-04 Bristol-Meyers Squibb Company Heterocyclic anti-migraine agents
WO2005073164A1 (en) 2004-01-30 2005-08-11 Peplin Biolipids Pty Ltd Therapeutic and carrier molecules
TW200533398A (en) 2004-03-29 2005-10-16 Bristol Myers Squibb Co Novel therapeutic agents for the treatment of migraine
DE102004063753A1 (de) 2004-12-29 2006-07-13 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung ausgewählter CGRP-Antagonisten in Kombination mit anderen Arzneistoffen gegen Migräne für die Behandlung von Migräne
AR053579A1 (es) 2005-04-15 2007-05-09 Genentech Inc Tratamiento de la enfermedad inflamatoria intestinal (eii)
US8008453B2 (en) 2005-08-12 2011-08-30 Amgen Inc. Modified Fc molecules
WO2007025286A2 (en) 2005-08-26 2007-03-01 The Board Of Trustees Of The Leland Stanford Junior University Therapy procedure for drug delivery for trigeminal pain
US8168592B2 (en) 2005-10-21 2012-05-01 Amgen Inc. CGRP peptide antagonists and conjugates
ES2433251T5 (es) 2005-11-14 2020-03-13 Teva Pharmaceuticals Int Gmbh Anticuerpos antagonistas dirigidos contra un péptido relacionado con el gen de la calcitonina y procedimientos que utilizan los mismos
EP1951042B1 (en) 2005-11-18 2012-10-10 Merck Sharp & Dohme Corp. Spirolactam tricyclic cgrp receptor antagonists
WO2007076336A1 (en) 2005-12-22 2007-07-05 Eli Lilly And Company Treatment of migraine with anti-cgrp antibodies
CN103073639A (zh) 2006-03-17 2013-05-01 比奥根艾迪克Ma公司 稳定的多肽组合物
BRPI0711352A2 (pt) 2006-05-09 2011-09-27 Merck & Co Inc composto, composição farmacêutica, e, métodos para o antagonismo de atividade receptora de cgrp em um mamìfero, e para, tratar, controlar, melhorar ou reduzir o risco de dor de cabeça, enxaqueca , ou cefaléia vascular
WO2008018472A1 (fr) * 2006-08-08 2008-02-14 Kyoto University Nouvel anticorps monoclonal et son utilisation
CN103275216B (zh) 2007-03-12 2015-05-06 艾斯巴技术-诺华有限责任公司 单链抗体的基于序列的工程改造和最优化
AU2008239754A1 (en) 2007-04-11 2008-10-23 Merck Sharp & Dohme Corp. CGRP receptor antagonists with tertiary amide, sulfonamide, carbamate and urea end groups
WO2008130524A1 (en) 2007-04-16 2008-10-30 Merck & Co., Inc. Aryl heterocyclic cgrp receptor antagonists
US8793074B2 (en) 2007-06-21 2014-07-29 Saint Louis University Sequence covariance networks, methods and uses therefor
DK2158315T3 (en) 2007-06-25 2016-06-06 Esbatech Alcon Biomed Res Unit Methods of modifying antibodies and modified antibodies with improved functional properties
WO2009033489A2 (en) 2007-09-11 2009-03-19 Glostrup Hospital Selective pacl inhibitors for use in the treatment of migraine and headaches
EP2299813B1 (en) 2008-06-12 2015-12-16 Merck Sharp & Dohme Corp. Branched 3- and 6-substituted quinolines as cgrp receptor antagonists
CA2730615A1 (en) 2008-07-18 2010-01-21 Galderma Research & Development Pacap signaling pathway modulators for treating inflammatory skin diseases with a neurogenic component, and more particularly rosacea and composition containing them
AU2009293471A1 (en) 2008-09-18 2010-03-25 Merck Sharp & Dohme Corp. Bicyclic dihydroimidazolone CGRP receptor antagonists
CA2738657A1 (en) 2008-10-03 2010-04-08 Merck Sharp & Dohme Corp. Cgrp receptor antagonists
CN101434649B (zh) 2008-12-12 2012-04-25 余榕捷 一种环七肽及其制备方法和应用
JO3382B1 (ar) 2008-12-23 2019-03-13 Amgen Inc أجسام مضادة ترتبط مع مستقبل cgrp بشري
KR20180052610A (ko) 2009-07-27 2018-05-18 노시셉터 엘엘씨 통증 치료 방법
JP2013514795A (ja) 2009-12-22 2013-05-02 ノバルティス アーゲー 治療における使用のための四価cd47抗体定常領域融合タンパク質
BR112012026021B1 (pt) * 2010-04-15 2022-05-03 Progenics Pharmaceuticals, Inc Anticorpos, seus fragmentos de ligação ao antígeno e seus usos, composições e uso das mesmas, linhagem de células de hibridoma, kit, ácido nucleico, e vetor de expressão
JO3330B1 (ar) 2010-06-10 2019-03-13 Lilly Co Eli الأجسام المضادة cgrp
JP5913307B2 (ja) 2010-07-12 2016-04-27 コヴェックス・テクノロジーズ・アイルランド・リミテッド 多機能性抗体複合体
MX348071B (es) 2011-03-16 2017-05-26 Amgen Inc Variantes de fc.
TWI838039B (zh) * 2011-03-28 2024-04-01 法商賽諾菲公司 具有交叉結合區定向之雙重可變區類抗體結合蛋白
SG10201604040PA (en) 2011-05-20 2016-07-28 Alderbio Holdings Llc Anti-cgrp compositions and use thereof
EP3539982B1 (en) 2011-12-23 2025-02-19 Pfizer Inc. Engineered antibody constant regions for site-specific conjugation and methods and uses therefor
MX374424B (es) 2012-05-21 2025-03-06 Genentech Inc Metodos para mejorar la seguridad del transporte de la barrera hematoencefalica.
US9546203B2 (en) * 2013-03-14 2017-01-17 Amgen Inc. Aglycosylated Fc-containing polypeptides with cysteine substitutions
MX2017003247A (es) 2014-09-15 2017-11-30 Amgen Inc Proteina de union a antigenos, bi-especificos del receptor anti-cgrp/receptor pac1 y usos de las mismas.
CN107708729A (zh) * 2015-04-15 2018-02-16 免疫医疗公司 用于治疗艰难梭菌(clostridium difficile)感染和相关疾病的方法
MX2017013113A (es) 2015-04-16 2018-07-06 Alder Biopharmaceuticals Inc Anticuerpos anti-pacap y sus usos.
TWI728953B (zh) 2015-04-24 2021-06-01 美商安美基公司 治療或預防偏頭痛之方法
US10822408B2 (en) 2015-12-15 2020-11-03 Amgen Inc. PACAP antibodies and uses thereof
WO2019140216A1 (en) * 2018-01-12 2019-07-18 Amgen Inc. Pac1 antibodies and uses thereof
US20220363770A1 (en) * 2019-06-28 2022-11-17 Amgen Inc. Anti-cgrp receptor/anti-pac1 receptor bispecific antigen binding proteins

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014144632A2 (en) * 2013-03-15 2014-09-18 Amgen Inc. Human pac1 antibodies

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