RU2509085C2 - Стабилизированные антитела против ангиопоэтина-2 и их применение - Google Patents

Стабилизированные антитела против ангиопоэтина-2 и их применение Download PDF

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RU2509085C2
RU2509085C2 RU2010135624/10A RU2010135624A RU2509085C2 RU 2509085 C2 RU2509085 C2 RU 2509085C2 RU 2010135624/10 A RU2010135624/10 A RU 2010135624/10A RU 2010135624 A RU2010135624 A RU 2010135624A RU 2509085 C2 RU2509085 C2 RU 2509085C2
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cancer
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antibody
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antibody according
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Ваэ БЕДИАН
Вилльям ДАЛЛЬ'АКВА
Херрен ВУ
Майкл БОУЭН
Джеффри БРАУН
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Медиммун Лимитед
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Abstract

Изобретение относится к области иммунологии. Представлено антитело против ангиопоэтина-2 (Ang-2), причем указанное антитело включает вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5) и вариабельную область легкой цепи, выбранную из SEQ ID No:3 (MEDI1); SEQ ID No:4 (MEDI2); SEQ ID No:5 (MEDI3); и SEQ ID No:6 (MEDI4). Раскрыта выделенная нуклеиновая кислота, кодирующая указанное антитело. Описана композиция для применения в ингибировании ангиогенеза раковой опухоли у животного, нуждающегося в этом, содержащая указанное выделенное антитело в терапевтически эффективном количестве и эксципиент. Предложенные вариантные антитела обладают повышенной стабильностью при хранении по сравнению с исходным антителом 3.19.3, из которого они получены, и способны конкурировать с Tie-2 за связывание с Ang-2. 3 н. и 9 з.п. ф-лы, 17 ил., 15 табл., 13 пр.

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Claims (12)

1. Выделенное антитело, которое связывается с ангиопоэтином-2 (Ang-2), причем антитело включает вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5) и вариабельную область легкой цепи:
a) SEQ ID No:3 (MEDI1);
b) SEQ ID No:4 (MEDI2);
c) SEQ ID No:5 (MEDI3) или
d) SEQ ID No:6 (MEDI4).
2. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1).
3. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:4 (MEDI2).
4. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:5 (MEDI3).
5. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:6 (MEDI4).
6. Антитело по п.1, причем антитело продуцируется с высокой эффективностью в клетках-хозяевах млекопитающих, которая равна или в 2 раза или более превышает эффективность продуцирования антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3).
7. Антитело по п.1, причем антитело проявляет скорость агрегации, которая по меньшей мере на 10% ниже скорости агрегации антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3), которую определяли в аналогичных экспериментальных условиях.
8. Антитело по п.1, причем антитело проявляет температуру плавления, которая является более высокой, чем температура плавления антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3).
9. Выделенная нуклеиновая кислота, кодирующая антитело по любому из пп.1-5, которое связывается с ангиопоэтином-2 (Ang-2).
10. Композиция для применения в ингибировании ангиогенеза раковой опухоли у животного, нуждающегося в этом, содержащая:
а) выделенное антитело по любому из пп.1-5 в терапевтически эффективном количестве и b) эксципиент.
11. Композиция по п.10, причем композиция дополнительно содержит один или несколько других противоопухолевых терапевтических агентов.
12. Композиция по п.10, где рак выбран из группы, состоящей из меланомы, рака ободочной кишки, колоректального рака, рака легких, мелкоклеточного рака легких, немелкоклеточного рака легких, рака молочной железы, рака прямой кишки, рака желудка, глиомы, рака предстательной железы, рака яичника, рака яичек, рака щитовидной железы, рака почек, рака печени, гепато-клеточного рака, рака поджелудочной железы, рака мозга, рака шеи, глиобластомы, эндометриального рака и рака центральной нервной системы.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2788088C1 (ru) * 2019-02-25 2023-01-16 Фармабцин Инк. Антитело против ang2 и его применение

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10254601A1 (de) 2002-11-22 2004-06-03 Ganymed Pharmaceuticals Ag Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung
EP2284194A1 (en) * 2004-12-21 2011-02-16 AstraZeneca AB Antibodies directed to angiopoietin-2 and uses thereof
US8557242B2 (en) 2008-01-03 2013-10-15 The Scripps Research Institute ERBB2 antibodies comprising modular recognition domains
US8454960B2 (en) 2008-01-03 2013-06-04 The Scripps Research Institute Multispecific antibody targeting and multivalency through modular recognition domains
SG10201605629VA (en) 2008-01-03 2016-08-30 Scripps Research Inst Antibody targeting through a modular recognition domain
US8574577B2 (en) 2008-01-03 2013-11-05 The Scripps Research Institute VEGF antibodies comprising modular recognition domains
US8557243B2 (en) 2008-01-03 2013-10-15 The Scripps Research Institute EFGR antibodies comprising modular recognition domains
MX2010008099A (es) * 2008-01-28 2010-08-04 Medimmune Ltd Anticuerpos y angiopoyetina-2 estabilizados y sus usos.
US20110190272A1 (en) * 2008-05-07 2011-08-04 Astrazeneca Ab Chemical compounds
JP5836120B2 (ja) 2008-05-20 2015-12-24 アヴァント・メディカル・コーポレーション オートインジェクタシステム
US8052645B2 (en) 2008-07-23 2011-11-08 Avant Medical Corp. System and method for an injection using a syringe needle
US8177749B2 (en) 2008-05-20 2012-05-15 Avant Medical Corp. Cassette for a hidden injection needle
US8133979B2 (en) * 2008-12-16 2012-03-13 Hoffmann-La Roche Inc. Antibodies against human angiopoietin 2
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
US8980268B2 (en) 2009-07-29 2015-03-17 Regeneron Pharamceuticals, Inc. Methods for treating cancer by administering an anti-Ang-2 antibody
US20120189635A1 (en) 2009-07-29 2012-07-26 Regeneron Pharmaceuticals, Inc. Methods for Treating or Preventing Malaria by Administering an Antibody that Specifically Binds Angiopoietin-2 (Ang-2)
WO2011044368A1 (en) * 2009-10-07 2011-04-14 Macrogenics, Inc. Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use
KR101688522B1 (ko) * 2009-12-15 2016-12-21 삼성전자주식회사 안지오포이에틴-2에 특이적으로 결합하는 항체 및 그의 용도
CA2791905A1 (en) 2010-03-01 2011-09-09 Caris Life Sciences Luxembourg Holdings, S.A.R.L. Biomarkers for theranostics
AU2011237669B2 (en) 2010-04-06 2016-09-08 Caris Life Sciences Switzerland Holdings Gmbh Circulating biomarkers for disease
WO2011134056A1 (en) * 2010-04-28 2011-11-03 Sunnybrook Health Sciences Centre Methods and uses of tie2 binding and/or activating agents
US20120100166A1 (en) 2010-07-15 2012-04-26 Zyngenia, Inc. Ang-2 Binding Complexes and Uses Thereof
US9512220B2 (en) 2011-04-05 2016-12-06 Neopharm Co., Ltd. Antibodies against angiopoietins 1 and 2, and their use
JP6038884B2 (ja) * 2011-04-20 2016-12-07 アムゲン・インコーポレーテッド 自動式注射装置
CN103857699B (zh) 2011-05-24 2016-08-31 泽恩格尼亚股份有限公司 多价和单价多特异性复合物及其用途
MX357393B (es) * 2012-01-23 2018-07-06 Regeneron Pharma Formulaciones estabilizadas que contienen anticuerpos anti - ang2.
US20150044227A1 (en) * 2012-03-08 2015-02-12 Medimmune, Llc Methods of treatment with angiopoietin-2 antibodies
USD898908S1 (en) 2012-04-20 2020-10-13 Amgen Inc. Pharmaceutical product cassette for an injection device
USD808010S1 (en) 2012-04-20 2018-01-16 Amgen Inc. Injection device
WO2013174403A1 (en) * 2012-05-23 2013-11-28 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of cancer
WO2013174404A1 (en) 2012-05-23 2013-11-28 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of cancer
AU2013285355A1 (en) * 2012-07-06 2015-01-29 Genmab B.V. Dimeric protein with triple mutations
JP6154900B2 (ja) 2012-07-13 2017-06-28 ロシュ グリクアート アクチェンゲゼルシャフト 二重特異性抗ｖｅｇｆ／抗ａｎｇ−２抗体及び眼血管疾患の処置におけるそれらの使用
MX369276B (es) 2012-11-13 2019-11-04 Biontech Ag Agentes para tratamiento de enfermedades cancerosas que expresan claudina.
JP2015536667A (ja) * 2012-12-03 2015-12-24 アルマック・ダイアグノスティクス・リミテッドＡｌｍａｃ Ｄｉａｇｎｏｓｔｉｃｓ Ｌｉｍｉｔｅｄ 癌のための分子診断検査
CA2895198A1 (en) * 2012-12-20 2014-06-26 Medimmune, Llc Liquid antibody formulation with improved aggregation properties
CA2907181C (en) 2013-03-15 2023-10-17 Viktor Roschke Multivalent and monovalent multispecific complexes and their uses
JP6768501B2 (ja) 2013-03-15 2020-10-14 アムゲン・インコーポレーテッド 薬物カセット、自動注入機、および自動注入機システム
JP6336564B2 (ja) 2013-03-15 2018-06-06 アムゲン・インコーポレーテッド 薬物カセット、自動注入器、および自動注入器システム
KR102060540B1 (ko) 2013-04-03 2019-12-31 삼성전자주식회사 항 c-Met 항체 및 항 Ang2 항체를 포함하는 병용 투여용 약학 조성물
EP2983695B1 (en) 2013-04-11 2019-05-29 Sunnybrook Research Institute Methods, uses and compositions of tie2 agonists
KR102131371B1 (ko) * 2013-07-02 2020-07-08 삼성전자주식회사 Ang-2 특이적 항체 및 그의 용도
EP2835380B2 (en) * 2013-07-29 2021-04-07 Samsung Electronics Co., Ltd Method of blocking vascular leakage using an anti-Ang2 antibody
KR102196450B1 (ko) * 2013-09-17 2020-12-30 삼성전자주식회사 Tie2와 결합을 유도하는 항 Ang2 항체를 포함하는 항암제
KR102206029B1 (ko) 2014-01-27 2021-01-20 삼성전자주식회사 Ang-2에 특이적으로 결합하는 항체 및 그의 용도
CA2946906A1 (en) * 2014-05-07 2015-11-12 Medimmune, Llc Methods of using anti-ang2 antibodies
AR100270A1 (es) 2014-05-19 2016-09-21 Lilly Co Eli Anticuerpos ang2
WO2016061551A1 (en) 2014-10-17 2016-04-21 Amgen Inc. Antibodies directed to angiopoietin-1 and angiopoietin-2 for ocular therapies
KR102543878B1 (ko) 2016-08-23 2023-06-14 메디뮨 리미티드 항-ｖｅｇｆ-ａ 및 항-ａｎｇ2 항체 및 이의 용도
EP3534940A1 (en) 2016-11-03 2019-09-11 Juno Therapeutics, Inc. Combination therapy of a cell based therapy and a microglia inhibitor
WO2018114728A1 (en) 2016-12-20 2018-06-28 F. Hoffmann-La Roche Ag Combination therapy with a bispecific anti-ang2/vegf antibody and a bispecific anti-her2 antibody
US11958913B2 (en) * 2017-01-09 2024-04-16 Biomunex Pharmaceuticals Polypeptide linker for preparing multispecific antibodies
CN111201438A (zh) 2017-06-02 2020-05-26 朱诺治疗学股份有限公司 与和细胞疗法相关的毒性有关的制品和方法
AU2018275894A1 (en) 2017-06-02 2019-12-12 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
CA3067602A1 (en) 2017-06-29 2019-01-03 Juno Therapeutics, Inc. Mouse model for assessing toxicities associated with immunotherapies
EP3676403A1 (en) 2017-09-01 2020-07-08 Juno Therapeutics, Inc. Gene expression and assessment of risk of developing toxicity following cell therapy
US11564946B2 (en) 2017-11-01 2023-01-31 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
JP2022513685A (ja) 2018-11-30 2022-02-09 ジュノー セラピューティクス インコーポレイテッド 養子細胞療法を用いた処置のための方法
WO2020113188A2 (en) 2018-11-30 2020-06-04 Juno Therapeutics, Inc. Methods for dosing and treatment of b cell malignancies in adoptive cell therapy
KR20220132527A (ko) 2019-12-06 2022-09-30 주노 쎄러퓨티크스 인코퍼레이티드 Ｂ 세포 악성 종양을 치료하기 위한 세포 요법과 연관된 독성 및 반응과 관련된 방법
CN113087696A (zh) * 2019-12-23 2021-07-09 江苏开元药业有限公司 喹啉类化合物及其应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1228086A1 (en) * 1999-11-12 2002-08-07 Amgen Inc. PROCESS FOR CORRECTION OF A DISULFIDE MISFOLD IN Fc MOLECULES
RU2242514C2 (ru) * 1996-07-02 2004-12-20 Ридженерон Фармасьютикалз, Инк. Изолированный tie-лиганд-4 и его изолированный фибриногеноподобный домен; изолированная молекула нуклеиновой кислоты, кодирующая указанный лиганд; вектор, содержащий указанную нуклеиновую кислоту; способ получения клетки-хозяина, трансформированной указанным вектором; способ получения tie-лиганда-4; конъюгат, содержащий указанный лиганд; лиганд-тело, содержащее указанный фибриногеноподобный домен
WO2006068953A2 (en) * 2004-12-21 2006-06-29 Astrazeneca Ab Antibodies directed to angiopoietin-2 and uses thereof
WO2007068895A1 (en) * 2005-12-15 2007-06-21 Astrazeneca Ab Combination of angiopoietin-2 antagonist and of vegf-a, kdr and/or flt1 antagonist for treating cancer

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5814464A (en) 1994-10-07 1998-09-29 Regeneron Pharma Nucleic acids encoding TIE-2 ligand-2
US5650490A (en) 1994-10-07 1997-07-22 Regeneron Pharmaceuticals, Inc. Tie-2 ligand 2
AU715621B2 (en) 1995-04-06 2000-02-03 Regeneron Pharmaceuticals, Inc. TIE-2 ligands, methods of making and uses thereof
ES2199804T3 (es) 1999-03-26 2004-03-01 Regeneron Pharmaceuticals, Inc. Modulacion de la permeabilidad vascular por medio de activadores del receptor tie2.
US6455035B1 (en) 1999-03-26 2002-09-24 Regeneron Pharmaceuticals, Inc. Angiopoietins and methods of use thereof
NZ516258A (en) 1999-06-07 2004-02-27 Immunex Corp Tek antagonists
US6521424B2 (en) 1999-06-07 2003-02-18 Immunex Corporation Recombinant expression of Tek antagonists
US7642278B2 (en) * 2001-07-03 2010-01-05 Novartis Vaccines And Diagnostics, Inc. Indazole benzimidazole compounds
US7205275B2 (en) 2001-10-11 2007-04-17 Amgen Inc. Methods of treatment using specific binding agents of human angiopoietin-2
US7658924B2 (en) * 2001-10-11 2010-02-09 Amgen Inc. Angiopoietin-2 specific binding agents
US7521053B2 (en) 2001-10-11 2009-04-21 Amgen Inc. Angiopoietin-2 specific binding agents
US7485297B2 (en) 2003-08-12 2009-02-03 Dyax Corp. Method of inhibition of vascular development using an antibody
PL2960253T3 (pl) * 2005-09-07 2018-11-30 Amgen Fremont Inc. Ludzkie przeciwciała monoklonalne przeciwko kinazie podobnej do receptora aktywiny-1
WO2007075323A2 (en) 2005-12-12 2007-07-05 Okalebo Lorna Ikel Systems and methods for maintaining and accessing medical information
WO2007109254A2 (en) * 2006-03-17 2007-09-27 Biogen Idec Ma Inc. Stabilized polypeptide compositions
AU2007249408A1 (en) * 2006-05-09 2007-11-22 Genentech, Inc. Binding polypeptides with optimized scaffolds
MX2010008099A (es) * 2008-01-28 2010-08-04 Medimmune Ltd Anticuerpos y angiopoyetina-2 estabilizados y sus usos.
EP2945343B1 (en) 2008-01-28 2019-06-19 BlackBerry Limited Providing session initiation protocol request contents method and system
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2242514C2 (ru) * 1996-07-02 2004-12-20 Ридженерон Фармасьютикалз, Инк. Изолированный tie-лиганд-4 и его изолированный фибриногеноподобный домен; изолированная молекула нуклеиновой кислоты, кодирующая указанный лиганд; вектор, содержащий указанную нуклеиновую кислоту; способ получения клетки-хозяина, трансформированной указанным вектором; способ получения tie-лиганда-4; конъюгат, содержащий указанный лиганд; лиганд-тело, содержащее указанный фибриногеноподобный домен
EP1228086A1 (en) * 1999-11-12 2002-08-07 Amgen Inc. PROCESS FOR CORRECTION OF A DISULFIDE MISFOLD IN Fc MOLECULES
WO2006068953A2 (en) * 2004-12-21 2006-06-29 Astrazeneca Ab Antibodies directed to angiopoietin-2 and uses thereof
WO2007068895A1 (en) * 2005-12-15 2007-06-21 Astrazeneca Ab Combination of angiopoietin-2 antagonist and of vegf-a, kdr and/or flt1 antagonist for treating cancer

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SERGEY М. KIPRIYANOV et al. Two amino acid mutations in an anti-human CD3 single chain Fv antibody fragment that affect the yield on bacterial secretion but not the affinity// Protein Engineering. - 1997, vol.10, no.4, pp.445-453. *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2788088C1 (ru) * 2019-02-25 2023-01-16 Фармабцин Инк. Антитело против ang2 и его применение

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