Endoglin polypeptides and uses thereof

Patent metadata

Field	Value
Publication number	US-9932386-B2
Application number	US-201214112620-A
Country	US
Kind code	B2
Filing date	Apr 19, 2012
Priority date	Apr 20, 2011
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a truncated, ligand-binding portion of the extracellular domain of endoglin (ENG) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders.

First claim

We claim:

1. An endoglin polypeptide consisting of an amino acid sequence beginning at an amino acid corresponding to any one of positions 26-42 of SEQ ID NO: 1and ending at an amino acid corresponding to any one of positions 346-378 of SEQ ID NO: 1.

2. The endoglin polypeptide of claim 1 , wherein the endoglin polypeptide consists of amino acids 26-346 of SEQ ID NO: 1.

3. The endoglin polypeptide of claim 1 , wherein the endoglin polypeptide consists of amino acids 26-359of SEQ ID NO: 1.

4. The endoglin polypeptide of claim 1 , wherein the endoglin polypeptide consists of amino acids 26-378of SEQ ID NO: 1.

5. An endoglin fusion protein comprising a first portion consisting of an endoglin polypeptide consisting of amino acids 26-346 of SEQ ID NO: 1 fused to a second portion that is heterologous to SEQ ID NO: 1.

6. The endoglin fusion protein of claim 5 , wherein the second portion comprises an Fc domain of an IgG.

7. The endoglin fusion protein of claim 6 , wherein the Fc domain is fused to the first portion by a linker.

8. The endoglin fusion protein of claim 7 wherein the linker consists of the amino acid sequence of SEQ ID NO: 31.

9. The endoglin fusion protein of claim 7 , wherein the linker consists of the amino acid sequence GGG.

10. The endoglin fusion protein of claim 5 wherein the second portion enhances one or more of in vivo stability, in vivo half-life, uptake/administration, tissue localization or distribution, formation of protein complexes, and/or purification.

11. The endoglin fusion protein of claim 5 , wherein the second portion is serum albumin.

12. An endoglin fusion protein comprising a first portion consisting of an endoglin polypeptide consisting of amino acids 26-359of SEQ ID NO: 1 fused to a second portion that is heterologous to SEQ ID NO: 1.

13. The endoglin fusion protein of claim 12 , wherein the second portion comprises an Fc domain of an IgG.

14. The endoglin fusion protein of claim 13 , wherein the Fc domain is fused to the first portion by a linker.

15. The endoglin fusion protein of claim 14 wherein the linker consists of the amino acid sequence of SEQ ID NO: 31.

16. The endoglin fusion protein of claim 14 , wherein the linker consists of the amino acid sequence GGG.

17. The endoglin fusion protein of claim 12 wherein the second portion enhances one or more of in vivo stability, in vivo half-life, uptake/administration, tissue localization or distribution, formation of protein complexes, and/or purification.

18. The endoglin fusion protein of claim 12 , wherein the second portion is serum albumin.

19. An endoglin fusion protein comprising a first portion consisting of an endoglin polypeptide consisting of amino acids 26-378 of SEQ ID NO: 1 fused to a second portion that is heterologous to SEQ ID NO: 1.

20. The endoglin fusion protein of claim 19 , wherein the second portion comprises an Fc domain of an IgG.

21. The endoglin fusion protein of claim 20 , wherein the Fc domain is fused to the first portion by a linker.

22. The endoglin fusion protein of claim 21 wherein the linker consists of the amino acid sequence of SEQ ID NO: 31.

23. The endoglin fusion protein of claim 21 , wherein the linker consists of the amino acid sequence GGG.

24. The endoglin fusion protein of claim 19 wherein the second portion enhances one or more of in vivo stability, in vivo half-life, uptake/administration, tissue localization or distribution, formation of protein complexes, and/or purification.

25. The endoglin fusion protein of claim 19 , wherein the second portion is serum albumin.

Assignees

• Grinberg Asya
• Castonguay Roselyne
• Werner Eric
• Kumar Ravindra
• Acceleron Pharma Inc

Inventors

• Grinberg Asya
• Castonguay Roselyne
• Werner Eric
• Kumar Ravindra

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• C07K2319/50

  containing protease site · CPC title