Monoclonal antibodies for enhancing or inhibiting insulin-like growth factor 1 (IGF-1)

Patent metadata

Field	Value
Publication number	US-9587024-B2
Application number	US-201514728379-A
Country	US
Kind code	B2
Filing date	Jun 2, 2015
Priority date	Aug 31, 2012
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

The present invention provides an antibody or antigen-binding fragment thereof that binds α v β 3 integrin, as well as methods of use in the treatment of diseases and disorders.

First claim

That which is claimed is:

1. An isolated polynucleotide comprising a nucleic acid sequence that encodes a polypeptide comprising a light chain variable region of an antibody or antigen binding fragment that binds the α v β 3 integrin cysteine loop (C-loop) domain of SEQ ID NO: 29, wherein the light chain variable region comprises:
(a) a light chain complementary determining region 1 (LCDR1) of SEQ ID NO: 1;
(b) a LCDR2 of SEQ ID NO: 2; and
(c) a LCDR3 of SEQ ID NO: 3.

2. The isolated polynucleotide of claim 1 , wherein the polypeptide comprises a sequence selected from the group consisting of: SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO: 47.

3. The isolated polynucleotide of claim 2 , wherein the polypeptide comprises SEQ ID NO: 14.

4. The isolated polynucleotide of claim 3 , wherein the polynucleotide further comprises a nucleic acid sequence that encodes a polypeptide comprising SEQ ID NO: 11, and wherein the polynucleotide encodes a Fv fragment or scFv.

5. The isolated polynucleotide of claim 3 , wherein the polynucleotide further comprises a nucleic acid sequence that encodes a polypeptide comprising SEQ ID NO: 12, and wherein the polynucleotide encodes a Fv fragment or scFv.

6. A vector comprising the polynucleotide of claim 3 and a polynucleotide comprising a nucleic acid sequence that encodes a polypeptide comprising SEQ ID NO: 11, wherein the vector encodes a Fv fragment or scFv.

7. An isolated host cell comprising the vector of claim 6 .

8. A vector comprising the polynucleotide of claim 3 and a polynucleotide comprising a nucleic acid sequence that encodes a polypeptide comprising SEQ ID NO: 12, wherein the vector encodes a Fv fragment or scFv.

9. An isolated host cell comprising the vector of claim 8 .

10. The isolated polynucleotide of claim 2 , wherein the polypeptide comprises SEQ ID NO: 16.

11. The isolated polynucleotide of claim 2 , wherein the polypeptide comprises SEQ ID NO: 47.

12. The isolated polynucleotide of claim 1 , wherein the polynucleotide comprises a sequence selected from the group consisting of: SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 46.

13. The isolated polynucleotide of claim 12 , wherein the polynucleotide comprises SEQ ID NO: 37.

14. The isolated polynucleotide of claim 13 , wherein the polynucleotide further comprises SEQ ID NO: 34, and wherein the polynucleotide encodes a Fv fragment or scFv.

15. The isolated polynucleotide of claim 13 , wherein the polynucleotide further comprises SEQ ID NO: 35, and wherein the polynucleotide encodes a Fv fragment or scFv.

16. A vector comprising the polynucleotide of claim 13 and a polynucleotide comprising a nucleic acid sequence comprising SEQ ID NO: 34, wherein the vector encodes a Fv fragment or scFv.

17. An isolated host cell comprising the vector of claim 16 .

18. A vector comprising the polynucleotide of claim 13 and a polynucleotide comprising a nucleic acid sequence comprising SEQ ID NO: 35, wherein the vector encodes a Fv fragment or scFv.

19. An isolated host cell comprising the vector of claim 18 .

20. The isolated polynucleotide of claim 12 , wherein the polynucleotide comprises SEQ ID NO: 46.

21. The isolated polynucleotide of claim 1 , wherein the polynucleotide further comprises a nucleic acid sequence that encodes a polypeptide comprising a heavy chain variable region, wherein the heavy chain variable region comprises:
(a) a heavy chain complementary determining region 1 (HCDR1) of SEQ ID NO: 4;
(b) a HCDR2 of SEQ ID NO: 5; and
(c) a HCDR3 of SEQ ID NO: 6, and
wherein the polynucleotide encodes a Fv fragment or single-chain Fv (scFv).

22. A vector comprising the polynucleotide of claim 1 .

23. An isolated host cell comprising the vector of claim 22 .

24. An isolated polynucleotide comprising a nucleic acid sequence that encodes a polypeptide comprising a heavy chain variable region of an antibody or antigen binding fragment that binds the α v β 3 integrin cysteine loop (C-loop) domain of SEQ ID NO: 29, wherein the polypeptide comprises a sequence selected from the group consisting of: SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 17, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 49.

25. The isolated polynucleotide of claim 24 , wherein the polypeptide comprises SEQ ID NO: 11.

26. The isolated polynucleotide of claim 24 , wherein the polypeptide comprises SEQ ID NO: 12.

27. The isolated polynucleotide of claim 24 , wherein the polypeptide comprises SEQ ID NO: 28.

28. The isolated polynucleotide of claim 24 , wherein the polypeptide comprises SEQ ID NO: 17.

29. The isolated polynucleotide of claim 24 , wherein the polypeptide comprises SEQ ID NO: 49.

30. The isolated polynucleotide of claim 24 , wherein the polynucleotide comprises a sequence selected from the group consisting of: SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO: 48.

31. The isolated polynucleotide of claim 30 , wherein the polynucleotide comprises SEQ ID NO: 34.

32. The isolated polynucleotide of claim 30 , wherein the polynucleotide comprises SEQ ID NO: 35.

33. The isolated polynucleotide of claim 30 , wherein the polynucleotide comprises SEQ ID NO: 48.

34. A vector comprising the polynucleotide of claim 24 .

35. An isolated host cell comprising the vector of claim 34 .

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Clemmons David
• Maile Laura
• Naso Michael
• Carr Francis J
• Jones Timothy D
• Keen Simon William

Classifications

• 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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

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