JP6060167B2 - 線維芽細胞増殖因子２１変異体 - Google Patents

線維芽細胞増殖因子２１変異体 Download PDF

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Publication number: JP6060167B2
Authority: JP; Japan
Prior art keywords: fgf21; variant; seq; amino acid; cells
Prior art date: 2011-10-04
Legal status (The legal status 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 status listed.): Active

Application number

JP2014534596A

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English (en)

Japanese (ja)

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JP2014530220A5 (2

JP2014530220A (ja

Inventor

クレイグ・デュアン・ディッキンソン

デイビッド・アルバート・ドライバー

ライアン・ジェイムズ・ダーリング

マルゴルザータ・ドナータ・ゴンシアルス

ラドミラ・ミカノビッチ

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イーライリリーアンドカンパニー

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2011-10-04

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2012-09-25

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2017-01-11

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2012-09-25 Application filed by イーライリリーアンドカンパニー, イーライリリーアンドカンパニー filed Critical イーライリリーアンドカンパニー

2014-11-17 Publication of JP2014530220A publication Critical patent/JP2014530220A/ja

2015-11-12 Publication of JP2014530220A5 publication Critical patent/JP2014530220A5/ja

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2017-01-11 Publication of JP6060167B2 publication Critical patent/JP6060167B2/ja

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QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Obesity (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hematology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Immunology (AREA)
Epidemiology (AREA)
Toxicology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)

JP2014534596A 2011-10-04 2012-09-25 線維芽細胞増殖因子２１変異体 Active JP6060167B2 (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US201161542906P	2011-10-04	2011-10-04
US61/542,906		2011-10-04
PCT/US2012/057053 WO2013052311A1 (en)	2011-10-04	2012-09-25	Fibroblast growth factor 21 variants

Publications (3)

Publication Number	Publication Date
JP2014530220A JP2014530220A (ja)	2014-11-17
JP2014530220A5 JP2014530220A5 (2)	2015-11-12
JP6060167B2 true JP6060167B2 (ja)	2017-01-11

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JP2014534596A Active JP6060167B2 (ja)	2011-10-04	2012-09-25	線維芽細胞増殖因子２１変異体

Country Status (28)

Country	Link
US (2)	US8541369B2 (2)
EP (1)	EP2763689B1 (2)
JP (1)	JP6060167B2 (2)
KR (1)	KR20140059271A (2)
CN (1)	CN103906530B (2)
AP (1)	AP2014007532A0 (2)
AR (1)	AR087973A1 (2)
AU (1)	AU2012318956A1 (2)
BR (1)	BR112014007532A2 (2)
CA (1)	CA2843520A1 (2)
CL (1)	CL2014000801A1 (2)
CO (1)	CO6910165A2 (2)
CR (1)	CR20140142A (2)
DO (1)	DOP2014000050A (2)
EA (1)	EA201490521A1 (2)
EC (1)	ECSP14013285A (2)
ES (1)	ES2548214T3 (2)
IL (1)	IL230754A0 (2)
IN (1)	IN2014CN00782A (2)
MA (1)	MA35458B1 (2)
MX (1)	MX2014004159A (2)
PE (1)	PE20142044A1 (2)
PH (1)	PH12014500740A1 (2)
SG (1)	SG11201401792UA (2)
TN (1)	TN2014000096A1 (2)
TW (1)	TWI461435B (2)
WO (1)	WO2013052311A1 (2)
ZA (1)	ZA201400882B (2)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2682147C (en)	2007-03-30	2017-08-08	Ambrx, Inc.	Modified fgf-21 polypeptides and their uses
WO2013006486A2 (en)	2011-07-01	2013-01-10	Ngm Biopharmaceuticals, Inc.	Compositions, uses and methods for treatment of metabolic disorders and diseases
KR20150002801A (ko) *	2012-05-15	2015-01-07	일라이 릴리 앤드 캄파니	섬유모세포 성장 인자 21 단백질의 치료 용도
CA2871656A1 (en)	2012-06-11	2013-12-19	Eli Lilly And Company	Fibroblast growth factor 21 variants
TWI513705B (zh)	2012-06-11	2015-12-21	Lilly Co Eli	纖維母細胞生長因子２１蛋白質
US9290557B2 (en)	2012-11-28	2016-03-22	Ngm Biopharmaceuticals, Inc.	Compositions comprising variants and fusions of FGF19 polypeptides
HK1214832A1 (zh)	2012-11-28	2016-08-05	恩格姆生物制药公司	用於代謝病症和疾病治療的組合物和方法
US9273107B2 (en)	2012-12-27	2016-03-01	Ngm Biopharmaceuticals, Inc.	Uses and methods for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
MX383664B (es)	2012-12-27	2025-03-14	Ngm Biopharmaceuticals Inc	Uso de un péptido para modular la homeostasis de los ácidos biliares o tratamiento de una enfermedad relacionada con los ácidos biliares.
WO2015065897A1 (en)	2013-10-28	2015-05-07	Ngm Biopharmaceuticals, Inc.	Cancer models and associated methods
PT3097122T (pt)	2014-01-24	2020-07-21	Ngm Biopharmaceuticals Inc	Anticorpos de ligação de domínio 2 de beta klotho e métodos de utilização dos mesmos
US20170065678A1 (en)	2014-03-11	2017-03-09	Novartis Ag	Methods of treating metabolic disorders associated with lipodystrophies and defects in insulin production or signaling
US10398758B2 (en)	2014-05-28	2019-09-03	Ngm Biopharmaceuticals, Inc.	Compositions comprising variants of FGF19 polypeptides and uses thereof for the treatment of hyperglycemic conditions
WO2015195509A2 (en)	2014-06-16	2015-12-23	Ngm Biopharmaceuticals, Inc.	Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
CN114129709A (zh)	2014-10-23	2022-03-04	恩格姆生物制药公司	包含肽变异体的药物组合物及其使用方法
SMT202100388T1 (it)	2014-10-24	2021-09-14	Bristol Myers Squibb Co	Polipeptidi fgf-21 modificati e loro usi
US10434144B2 (en)	2014-11-07	2019-10-08	Ngm Biopharmaceuticals, Inc.	Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders
WO2017019957A2 (en)	2015-07-29	2017-02-02	Ngm Biopharmaceuticals, Inc.	Binding proteins and methods of use thereof
JP6728352B2 (ja)	2015-11-09	2020-07-22	エヌジーエムバイオファーマシューティカルス，インコーポレーテッド	胆汁酸に関係した障害の治療方法
TW201731867A (zh) *	2015-12-02	2017-09-16	賽諾菲公司	Ｆｇｆ２１變異體
WO2017220706A1 (en) *	2016-06-22	2017-12-28	Novo Nordisk A/S	Pharmaceutical compositions of fgf21 derivatives and uses thereof
EP3503882A4 (en)	2016-08-26	2020-07-29	NGM Biopharmaceuticals, Inc.	METHOD FOR TREATING FIBROBLAST GROWTH FACTOR-19-MEDIATED CARCINOMAS AND TUMORS
CN106220724B (zh) *	2016-09-13	2019-10-11	河南师范大学	人成纤维细胞生长因子21重组蛋白及其制备方法和应用
CN106397607A (zh) *	2016-09-13	2017-02-15	河南师范大学	重组人成纤维细胞生长因子21融合蛋白及其在制备治疗代谢疾病药物中的应用
CN106432509B (zh) *	2016-09-13	2019-05-21	河南师范大学	一种治疗代谢疾病的重组人成纤维细胞生长因子21融合蛋白及其制备方法和应用
EP4470551A3 (en)	2017-03-14	2025-02-26	Sunshine Lake Pharma Co., Ltd.	Dual-target fusion proteins comprising the fc portion of an immunoglobulin
MX2020002206A (es)	2017-09-08	2020-07-20	Bristol Myers Squibb Co	Factor de crecimiento de fibroblastos 21 (fgf-21) modificado para usarse en metodos para tratar la esteatohepatitis no alcoholica (nash).
US20200376080A1 (en)	2017-12-22	2020-12-03	Novartis Ag	Methods of treating metabolic disorders with fgf21 variants
AU2019218147B2 (en) *	2018-02-08	2023-06-08	Sunshine Lake Pharma Co., Ltd.	FGF21 variant, fusion protein and application thereof
CA3104686A1 (en) *	2018-07-03	2020-01-09	Bristol-Myers Squibb Company	Fgf-21 formulations
CN109836486B (zh) *	2019-01-30	2020-09-08	北京双因生物科技有限公司	成纤维生长因子21变体、其融合蛋白及其用途
CN111662373B (zh) *	2019-03-05	2024-05-14	广东东阳光药业股份有限公司	一种多肽分子及其应用
CN114853908B (zh)	2019-05-16	2024-06-07	浙江道尔生物科技有限公司	一种治疗代谢疾病的融合蛋白
IL294534A (en)	2020-01-08	2022-09-01	Bristol Myers Squibb Co	Fgf-21 conjugate formulations
CN115322794B (zh)	2020-01-11	2025-09-19	北京质肽生物医药科技有限公司	Glp-1和fgf21的融合蛋白的缀合物
JP2023538533A (ja)	2020-08-07	2023-09-08	ブリストル－マイヤーズスクイブカンパニー	線維症の処置のための、ｃｃｒ２／５拮抗剤と組み合わせたｆｇｆ２１
KR102495299B1 (ko) *	2020-11-03	2023-02-06	토드제약 주식회사	Fgf21의 열탄력성을 이용한 fgf21 생산 방법
US20240123031A1 (en)	2020-11-25	2024-04-18	Bristol-Myers Squibb Company	Methods of treating liver diseases
CA3224743A1 (en)	2021-07-14	2023-01-19	Beijing Ql Biopharmaceutical Co., Ltd.	Fusion polypeptides for metabolic disorders

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8601597D0 (en)	1986-01-23	1986-02-26	Wilson R H	Nucleotide sequences
US7459540B1 (en)	1999-09-07	2008-12-02	Amgen Inc.	Fibroblast growth factor-like polypeptides
WO2003011213A2 (en)	2001-07-30	2003-02-13	Eli Lilly And Company	Method for treating diabetes and obesity
CN1890371A (zh) *	2003-12-10	2007-01-03	伊莱利利公司	成纤维细胞生长因子的21突变蛋白
WO2006028714A1 (en)	2004-09-02	2006-03-16	Eli Lilly And Company	Muteins of fibroblast growth factor 21
EA011390B1 (ru) *	2004-09-02	2009-02-27	Эли Лилли Энд Компани	Мутантные белки (мутеины) фактора роста фибробластов 21
CA2682147C (en)	2007-03-30	2017-08-08	Ambrx, Inc.	Modified fgf-21 polypeptides and their uses
EP2296690B1 (en) *	2008-06-04	2016-11-30	Amgen, Inc	Fgf21 mutants and uses thereof
WO2010065439A1 (en) *	2008-12-05	2010-06-10	Eli Lilly And Company	Variants of fibroblast growth factor 21
EP2427207B1 (en)	2009-05-05	2017-08-16	Amgen, Inc	Fgf21 mutants and uses thereof
HRP20240135T1 (hr)	2009-05-05	2024-04-12	Amgen Inc.	Fgf21 mutanti i njihove upotrebe

2012
- 2012-09-20 AR ARP120103466A patent/AR087973A1/es unknown
- 2012-09-21 TW TW101134800A patent/TWI461435B/zh not_active IP Right Cessation
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- 2012-09-25 AU AU2012318956A patent/AU2012318956A1/en not_active Abandoned
- 2012-09-25 CN CN201280048530.2A patent/CN103906530B/zh not_active Expired - Fee Related
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- 2012-09-25 BR BR112014007532A patent/BR112014007532A2/pt not_active IP Right Cessation
- 2012-09-25 CA CA2843520A patent/CA2843520A1/en not_active Abandoned
- 2012-09-25 PH PH1/2014/500740A patent/PH12014500740A1/en unknown
- 2012-09-25 WO PCT/US2012/057053 patent/WO2013052311A1/en not_active Ceased
- 2012-09-25 IN IN782CHN2014 patent/IN2014CN00782A/en unknown
- 2012-09-25 PE PE2014000472A patent/PE20142044A1/es not_active Application Discontinuation
- 2012-09-25 JP JP2014534596A patent/JP6060167B2/ja active Active
- 2012-09-25 US US13/626,308 patent/US8541369B2/en active Active
- 2012-09-25 KR KR1020147008644A patent/KR20140059271A/ko not_active Withdrawn
- 2012-09-25 MX MX2014004159A patent/MX2014004159A/es unknown
- 2012-09-25 SG SG11201401792UA patent/SG11201401792UA/en unknown
- 2012-09-25 EA EA201490521A patent/EA201490521A1/ru unknown
- 2012-09-25 AP AP2014007532A patent/AP2014007532A0/xx unknown
2013
- 2013-08-13 US US13/965,243 patent/US8883726B2/en active Active
2014
- 2014-01-30 IL IL230754A patent/IL230754A0/en unknown
- 2014-02-05 ZA ZA2014/00882A patent/ZA201400882B/en unknown
- 2014-03-06 DO DO2014000050A patent/DOP2014000050A/es unknown
- 2014-03-06 TN TNP2014000096A patent/TN2014000096A1/en unknown
- 2014-03-17 CO CO14057034A patent/CO6910165A2/es unknown
- 2014-03-27 MA MA36861A patent/MA35458B1/fr unknown
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EP2763689B1 (en)	2015-08-12
DOP2014000050A (es)	2014-04-15
AR087973A1 (es)	2014-04-30
ECSP14013285A (es)	2014-05-31
US8883726B2 (en)	2014-11-11
EP2763689A1 (en)	2014-08-13
SG11201401792UA (en)	2014-08-28
PH12014500740A1 (en)	2020-10-19
WO2013052311A1 (en)	2013-04-11
AP2014007532A0 (en)	2014-03-31
MA35458B1 (fr)	2014-09-01
US8541369B2 (en)	2013-09-24
BR112014007532A2 (pt)	2017-04-04
EA201490521A1 (ru)	2014-07-30
US20130324460A1 (en)	2013-12-05
IN2014CN00782A (2)	2015-04-03
ZA201400882B (en)	2016-02-24
AU2012318956A1 (en)	2014-02-06
KR20140059271A (ko)	2014-05-15
TWI461435B (zh)	2014-11-21
IL230754A0 (en)	2014-03-31
TN2014000096A1 (en)	2015-07-01
CL2014000801A1 (es)	2014-09-12
CR20140142A (es)	2014-05-02
JP2014530220A (ja)	2014-11-17
TW201326198A (zh)	2013-07-01
ES2548214T3 (es)	2015-10-14
CN103906530A (zh)	2014-07-02
MX2014004159A (es)	2015-02-12
CN103906530B (zh)	2016-01-20
CO6910165A2 (es)	2014-03-31
PE20142044A1 (es)	2014-12-06
US20130085098A1 (en)	2013-04-04

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