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