WO2016048999A3 - Fgf21 truncations and mutants and uses thereof - Google Patents

Fgf21 truncations and mutants and uses thereof Download PDF

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Publication number
WO2016048999A3
WO2016048999A3 PCT/US2015/051406 US2015051406W WO2016048999A3 WO 2016048999 A3 WO2016048999 A3 WO 2016048999A3 US 2015051406 W US2015051406 W US 2015051406W WO 2016048999 A3 WO2016048999 A3 WO 2016048999A3
Authority
WO
WIPO (PCT)
Prior art keywords
proteins
fgf21
mutant
treat
blood glucose
Prior art date
Application number
PCT/US2015/051406
Other languages
French (fr)
Other versions
WO2016048999A2 (en
Inventor
Ronald M. Evans
Michael Downes
Annette Atkins
Original Assignee
Salk Institute For Biological Studies
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 Salk Institute For Biological Studies filed Critical Salk Institute For Biological Studies
Publication of WO2016048999A2 publication Critical patent/WO2016048999A2/en
Publication of WO2016048999A3 publication Critical patent/WO2016048999A3/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1825Fibroblast growth factor [FGF]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475Growth factors; Growth regulators
    • C07K14/50Fibroblast growth factor [FGF]

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

The present disclosure provides FGF21 mutant proteins, such as those having an N- terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Thus, the disclosed mutant FGF21 proteins can be used to treat one or more metabolic diseases. In some examples, mutant FGF21 proteins have reduced receptor specificity and/or reduced receptor affinity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels, for example to treat a metabolic disorder are also provided.
PCT/US2015/051406 2014-09-23 2015-09-22 Fgf21 truncations and mutants and uses thereof WO2016048999A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462053987P 2014-09-23 2014-09-23
US62/053,987 2014-09-23

Publications (2)

Publication Number Publication Date
WO2016048999A2 WO2016048999A2 (en) 2016-03-31
WO2016048999A3 true WO2016048999A3 (en) 2016-10-27

Family

ID=55582240

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2015/051406 WO2016048999A2 (en) 2014-09-23 2015-09-22 Fgf21 truncations and mutants and uses thereof

Country Status (1)

Country Link
WO (1) WO2016048999A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
MX2021000016A (en) 2018-07-03 2021-03-09 Bristol Myers Squibb Co Fgf21 formulations.
JP2022522787A (en) * 2019-03-05 2022-04-20 サンシャイン・レイク・ファーマ・カンパニー・リミテッド Polypeptide molecules and their applications
US20240165202A1 (en) * 2021-03-19 2024-05-23 Sunshine Lake Pharma Co., Ltd. Uses of fgf21 polypeptides and fusion polypeptides thereof

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006028714A1 (en) * 2004-09-02 2006-03-16 Eli Lilly And Company Muteins of fibroblast growth factor 21
WO2010129600A2 (en) * 2009-05-05 2010-11-11 Amgen Inc. Fgf21 mutants and uses thereof
WO2012062078A1 (en) * 2010-11-11 2012-05-18 重庆富进生物医药有限公司 N-terminal deletion variant of human fibroblast growth factor 21 and conjugate thereof
WO2012066075A1 (en) * 2010-11-19 2012-05-24 Novartis Ag Methods of treating fgf21-associated disorders
WO2013033452A2 (en) * 2011-08-31 2013-03-07 Amgen Inc. Method of treating or ameliorating type 1 diabetes using fgf21
WO2013131091A1 (en) * 2012-03-02 2013-09-06 New York University Chimeric fgf21 proteins with enhanced binding affinity for beta-klotho for the treatment of type ii diabetes, obesity and related metabolic disorders

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006028714A1 (en) * 2004-09-02 2006-03-16 Eli Lilly And Company Muteins of fibroblast growth factor 21
WO2010129600A2 (en) * 2009-05-05 2010-11-11 Amgen Inc. Fgf21 mutants and uses thereof
WO2012062078A1 (en) * 2010-11-11 2012-05-18 重庆富进生物医药有限公司 N-terminal deletion variant of human fibroblast growth factor 21 and conjugate thereof
WO2012066075A1 (en) * 2010-11-19 2012-05-24 Novartis Ag Methods of treating fgf21-associated disorders
WO2013033452A2 (en) * 2011-08-31 2013-03-07 Amgen Inc. Method of treating or ameliorating type 1 diabetes using fgf21
WO2013131091A1 (en) * 2012-03-02 2013-09-06 New York University Chimeric fgf21 proteins with enhanced binding affinity for beta-klotho for the treatment of type ii diabetes, obesity and related metabolic disorders

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ADAMS, A.C. ET AL.: "LY2405319, an Engineered FGF21 Variant, Improves the Metabolic Status of Diabetic Monkeys", PLOS ONE, vol. 8, no. 6, 2013, pages e65763, XP055268886 *

Also Published As

Publication number Publication date
WO2016048999A2 (en) 2016-03-31

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