GDF15 fusion proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-11208464-B2
Application number	US-201916412819-A
Country	US
Kind code	B2
Filing date	May 15, 2019
Priority date	May 10, 2016
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

Abstract

Fusion proteins containing a half-life extension protein, a linker, and a GDF15 protein are described. Also described are nucleic acids encoding the fusion proteins, recombinant cells thereof, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing metabolic diseases, disorders or conditions.

First claim

We claim:

1. A method of treating obesity, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a fusion protein comprising:
a. the amino acid sequence of SEQ ID NO:2;
b. a linker having a length of 35-48 amino acids and comprising the amino acid sequence of (GGGGS)n, wherein n is 7 or 8 (SEQ ID NO:42 or SEQ ID NO:43); and
c. a truncated GDF15 consisting of the amino acid sequence of SEQ ID NO:8; wherein the fusion protein is arranged from N-terminus to C-terminus in the order (a)-(b)-(c), and the C-terminus of the amino acid sequence of SEQ ID NO:2 is fused to the N-terminus of the truncated GDF15 through the linker.

2. The method of claim 1 , wherein the linker comprises the sequence (GGGGS)n, wherein n is 8 (SEQ ID NO:43).

3. The method of claim 2 , wherein the linker consists of the amino acid sequence of SEQ ID NO:12.

4. The method of claim 3 , wherein the pharmaceutical composition comprises the fusion protein comprising the amino acid sequence of SEQ ID NO:92.

5. A method of treating type 2 diabetes, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a fusion protein comprising:
a. the amino acid sequence of SEQ ID NO:2;
b. a linker having a length of 35-48 amino acids and comprising the amino acid sequence of (GGGGS)n, wherein n is 7 or 8 (SEQ ID NO:42 or SEQ ID NO:43); and
c. a truncated GDF15 consisting of the amino acid sequence of SEQ ID NO:8;

wherein the fusion protein is arranged from N-terminus to C-terminus in the order (a)-(b)-(c), and the C-terminus of the amino acid sequence of SEQ ID NO:2 is fused to the N-terminus of the truncated GDF15 through the linker.

6. The method of claim 5 , wherein the linker comprises the sequence (GGGGS)n, wherein n is 8 (SEQ ID NO:43).

7. The method of claim 6 , wherein the linker consists of the amino acid sequence of SEQ ID NO:12.

8. The method of claim 7 , wherein the pharmaceutical composition comprises the fusion protein comprising the amino acid sequence of SEQ ID NO:92.

9. A method of reducing food intake, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a fusion protein and a pharmaceutically acceptable, wherein the fusion protein comprises:
a. the amino acid sequence of SEQ ID NO:2;
b. a linker having a length of 35-48 amino acids and comprising the amino acid sequence of (GGGGS)n, wherein n is 7 or 8 (SEQ ID NO:42 or SEQ ID NO: 43); and
c. a truncated GDF15 consisting of the amino acid sequence of SEQ ID NO:8;

wherein the fusion protein is arranged from N-terminus to C-terminus in the order (a)-(b)-(c), and the C-terminus of the amino acid sequence of SEQ ID NO:2 is fused to the N-terminus of the truncated GDF15 through the linker.

10. The method of claim 9 , wherein the linker comprises the sequence (GGGGS)n, wherein n is 8 (SEQ ID NO:43).

11. The method of claim 10 , wherein the linker consists of the amino acid sequence of SEQ ID NO:12.

12. The method of claim 11 , wherein the pharmaceutical composition comprises the fusion protein comprising the amino acid sequence of SEQ ID NO:92.

13. A method of reducing body weight, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a fusion protein and a pharmaceutically acceptable, wherein the fusion protein comprises:
a. the amino acid sequence of SEQ ID NO:2;
b. a linker having a length of 35-48 amino acids and comprising the amino acid sequence of (GGGGS)n, wherein n is 7 or 8 (SEQ ID NO:42 or SEQ ID NO:43); and
c. a truncated GDF15 consisting of the amino acid sequence of SEQ ID NO:8;

wherein the fusion protein is arranged from N-terminus to C-terminus in the order (a)-(b)-(c), and the C-terminus of the amino acid sequence of SEQ ID NO:2 is fused to the N-terminus of the truncated GDF15 through the linker.

14. The method of claim 13 , wherein the linker comprises the sequence (GGGGS)n, wherein n is 8 (SEQ ID NO: 43).

15. The method of claim 14 , wherein the linker consists of the amino acid sequence of SEQ ID NO: 12.

16. The method of claim 15 , wherein the pharmaceutical composition comprises the fusion protein comprising the amino acid sequence of SEQ ID NO:92.

17. A method of reducing blood glucose level, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a fusion protein and a pharmaceutically acceptable, wherein the fusion protein comprises:
a. the amino acid sequence of SEQ ID NO:2;
b. a linker having a length of 35-48 amino acids and comprising the amino acid sequence of (GGGGS)n, wherein n is 7 or 8 (SEQ ID NO:42 or SEQ ID NO:43); and
c. a truncated GDF15 consisting of the amino acid sequence of SEQ ID NO:8;

wherein the fusion protein is arranged from N-terminus to C-terminus in the order (a)-(b)-(c), and the C-terminus of the amino acid sequence of SEQ ID NO:2 is fused to the N-terminus of the truncated GDF15 through the linker.

18. The method of claim 17 , wherein the linker comprises the sequence (GGGGS)n, wherein n is 8 (SEQ ID NO:43).

19. The method of claim 18 , wherein the linker consists of the amino acid sequence of SEQ ID NO:12.

20. The method of claim 19 , wherein the pharmaceutical composition comprises the fusion protein comprising the amino acid sequence of SEQ ID NO:92.

Assignees

• Janssen Biotech Inc
• Janssen Sciences Ireland Unlimited Co

Inventors

• Armstrong Anthony
• Connor Judith Ann
• Furman Jennifer
• Huang Chichi
• Hunter Michael J
• Lin-Schmidt Xiefan
• Nelson Serena
• Rangwala Shamina M
• Mullican Shannon
• Chavez Jose Antonio

Classifications

• C07K14/475 Primary

  Growth factors; Growth regulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/46

  from vertebrates · CPC title

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title