Methods of treating metabolic disorders associated with lipodystrophies and defects in insulin production or signaling
US-2017065678-A1 · Mar 9, 2017 · US
Methods of treating metabolic disorders with dual function fibroblast growth factor 21 proteins
US10669323B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10669323-B2 |
| Application number | US-201615248712-A |
| Country | US |
| Kind code | B2 |
| Filing date | Aug 26, 2016 |
| Priority date | Sep 26, 2011 |
| Publication date | Jun 2, 2020 |
| Grant date | Jun 2, 2020 |
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- Title
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Abstract
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The present invention relates to the identification of dual function fusion proteins comprising fibroblast growth factor 21 (FGF21) and Exenatide, Exendin-4, or GLP-1. Also disclosed are methods for treating metabolic, cardiovascular, and endocrine conditions related to glucose and/or lipid homeostasis.
First claim
Opening claim text (preview).
What is claimed is: 1. A method of treating a metabolic disorder by administering to a subject in need thereof a dual function fusion protein, wherein the dual function fusion protein comprises a GLP-1 receptor agonist, an FGF21 receptor agonist, and an Fc domain attached to each other via a GS linker, having an orientation of N-terminus-GLP-1 receptor agonist-linker-Fc domain-linker-FGF21 receptor agonist-C-terminus; and wherein the metabolic disorder is obesity, type 2 diabetes mellitus, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), insulin resistance, hyperinsulinemia, glucose intolerance, or hyperglycemia. 2. The method of claim 1 , wherein the dual function fusion protein comprises the amino acid sequence of SEQ ID NO:36. 3. The method of claim 1 , wherein the dual function fusion protein comprises the amino acid sequence of SEQ ID NO:134. 4. The method of claim 1 , wherein the dual function fusion protein comprises the amino acid sequence of SEQ ID NO:135. 5. The method of claim 1 , wherein the GLP-1 receptor agonist is selected from wild-type GLP-1, Exendin-4, GLP-1 variants, and Exendin-4 analogues. 6. The method of claim 1 , wherein the FGF21 receptor agonist is selected from FGF21 variants comprising the following amino acid sequences: (a) (SEQ ID NO: 185) DSSPLLQFGG QVRQRYLYTD DAQETEAHLE IREDGTVGGA AHQSPESLLE LKALKPGVIQ ILGVKTSRFL CQKPDGALYG SLHFDPEACS FRELLLEDGY NVYQSEAHGL PLHLPGNRSP HCDPAPQGPA RFLPLPGLPP ALPEPPGILA PQPPDVGSSD PLAMVGPSQG RSPSYAS; (b) (SEQ ID NO: 186) DSSPLLQFGG QVRQRYLYTD DAQETEAHLE IREDGTVGGA AHQSPESLLE LKALKPGVIQ ILGVKTSRFL CQKPDGALYG SLHFDPEACS FRELLLEDGY NVYQSEAHGL PLHLPGNRSP HCDPAPQGPA RFLPLPGLPP ALPEPPGILA PQPPDVGSSD PLAMVGGSQG RSPSYAS; (c) (SEQ ID NO: 187) D SSPLLQFGGQ VRQRYLYTDD ACQTEAHLEI REDGTVGGAA DQSPESLLQL KALKPGVIQI LGVKTSRFLC QRPDGTLYGS LHFDPEACSF RELLLEDGYN VYQSEAHGLP LHLPCNRSPH RDPASRGPAR FLPLPGLPPA LPEPPGILAP QPPDVGSSDP LAMVGGSQAR SPSYAS; and (d) (SEQ ID NO: 188) D SSPLLQFGGQ VRQRYLYTDD ACQTEAHLEI REDGTVGGAA DQSPESLLQL KALKPGVIQI LGVKTSRFLC QKPDGALYGS LHFDPEACSF RELLLEDGYN VYQSEAHGLP LHLPCNRSPH RDPASRGPAR FLPLPGLPPA LPEPPGILAP QPPDVGSSDP LAMVGGSQAR SPSYAS. 7. The method of claim 1 , wherein the metabolic disorder is obesity. 8. The method of claim 1 , wherein the metabolic disorder is type 2 diabetes mellitus. 9. The method of claim 1 , wherein the metabolic disorder is dyslipidemia. 10. The method of claim 1 , wherein the metabolic disorder is nonalcoholic fatty liver disease (NAFLD). 11. The method of claim 1 , wherein the metabolic disorder is nonalcoholic steatohepatitis (NASH). 12. The method of claim 1 , wherein the metabolic disorder is insulin resistance. 13. The method of claim 1 , wherein the metabolic disorder is hyperinsulinemia. 14. The method of claim 1 , wherein the metabolic disorder is glucose intolerance. 15. The method of claim 1 , wherein the metabolic disorder is hyperglycemia.
Assignees
Inventors
Classifications
Fusion polypeptide · CPC title
Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title
containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones · CPC title
- C07K14/605Primary
Glucagons · CPC title
- C07K14/50Primary
Fibroblast growth factor [FGF] · CPC title
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Frequently asked questions
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- What does patent US10669323B2 cover?
- The present invention relates to the identification of dual function fusion proteins comprising fibroblast growth factor 21 (FGF21) and Exenatide, Exendin-4, or GLP-1. Also disclosed are methods for treating metabolic, cardiovascular, and endocrine conditions related to glucose and/or lipid homeostasis.
- Who is the assignee on this patent?
- Boettcher Brian R, Caplan Shari Lynn, Cellitti Susan E, and 7 more
- What technology area does this patent fall under?
- Primary CPC classification C07K14/605. Mapped technology areas include Chemistry & Metallurgy.
- When was this patent published?
- Publication date Tue Jun 02 2020 00:00:00 GMT+0000 (Coordinated Universal Time) (B2). Legal status and post-grant events are not shown on this page.
- What related patents are in patentsdb?
- We list 7 related publications on this page (citations in our corpus or others sharing the same primary CPC).