Neutralizing human anti-IGFR antibody
View Patent ↗The present invention includes fully human, neutralizing, monoclonal antibodies against human Insulin-like Growth Factor Receptor-I (IGFR1). The antibodies are useful for treating or preventing cancer in a subject. Also included are methods of using and producing the antibodies of the invention.
1. A method for producing a polypeptide comprising amino acids 20-137 of SEQ ID NO: 45;
comprising introducing a polynucleotide encoding said polypeptide into a host cell under conditions wherein said polypeptide is produced in said host cell.
2. The method of claim 1 wherein the host cell is a eukaryotic cell.
3. The method of claim 2 wherein said host cell is Chinese hamster ovary cell.
4. The method of claim 1 wherein the host cell is a fungal cell.
5. The method of claim 1 wherein said polypeptide is isolated from said cell.
6. The method of claim 1 wherein the polynucleotide encoding said polypeptide is operably associated with a CMV promoter.
7. The method of claim 1 wherein the polynucleotide is in a vector.
8. The method of claim 7 wherein the vector comprises a DHFR gene.
9. The method of claim 8 wherein the DHFR gene is operably linked to a mouse mammary tumor virus long terminal repeat promoter.
10. The method of claim 7 wherein the vector comprises a hygromycin B gene.
11. The method of claim 10 wherein the hygromycin B gene is operably linked to a TK promoter.
12. The method of claim 1 for producing a polypeptide comprising amino acids 20-137 of SEQ ID NO: 45; comprising introducing a vector comprising a polynucleotide encoding said polypeptide, operably linked to a CMV promoter, into a Chinese hamster ovary cell under conditions wherein said polypeptide is produced in said host cell and isolating said polypeptide.
13. The method of claim 12 wherein the vector comprises a DHFR gene.
14. The method of claim 12 wherein the DHFR gene is operably linked to a mouse mammary tumor virus long terminal repeat promoter.
15. The method of claim 12 wherein the vector comprises a hygromycin B gene.
16. The method of claim 15 wherein the hygromycin B gene is operably linked to a TK promoter.
17. The method of claim 1 further comprising producing a polypeptide comprising amino acids 20-128 of SEQ ID NO: 78; comprising introducing a polynucleotide encoding said polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 into a host cell under conditions wherein said polypeptide is produced in said host cell.
18. The method of claim 17 wherein the host cell is a eukaryotic cell.
19. The method of claim 18 wherein said host cell is Chinese hamster ovary cell.
20. The method of claim 17 wherein the host cell is a fungal cell.
21. The method of claim 17 wherein said polypeptide is isolated from said cell.
22. The method of claim 17 wherein the polynucleotide encoding said polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 is operably associated with a CMV promoter.
23. The method of claim 17 wherein the polynucleotide encoding said polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 is in a vector.
24. The method of claim 23 wherein the vector comprises a DHFR gene.
25. The method of claim 24 wherein the DHFR gene is operably linked to a mouse mammary tumor virus long terminal repeat promoter.
26. The method of claim 23 wherein the vector comprises a hygromycin B gene.
27. The method of claim 26 wherein the hygromycin B gene is operably linked to a TK promoter.
28. The method of claim 17 comprising introducing one or more vectors comprising one or more polynucleotides encoding said polypeptides, each operably linked to a CMV promoter, into a Chinese hamster ovary cell under conditions wherein said polypeptides are produced in said host cell and isolating said polypeptides.
29. The method of claim 28 wherein said one or more vectors comprises a DHFR gene.
30. The method of claim 29 wherein the DHFR gene is operably linked to a mouse mammary tumor virus long terminal repeat promoter.
31. The method of claim 28 wherein said one or more vectors comprises a hygromycin B gene.
32. The method of claim 31 wherein the hygromycin B gene is operably linked to a TK promoter.
33. The method of claim 28 wherein said one or more vectors comprises a DHFR gene operably linked to a mouse mammary tumor virus long terminal repeat promoter; and a hygromycin B gene operably linked to a TK promoter.
34. The method of claim 28 wherein the polypeptide comprising amino acids 20-137 of SEQ ID NO: 45 is linked to a gamma-1 heavy chain immunoglobulin constant region and the polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 is linked to a kappa light chain immunoglobulin constant region.
35. The method of claim 34 further comprising combining said polypeptide comprising amino acids 20-137 of SEQ ID NO: 45 linked to a gamma-1 heavy chain immunoglobulin constant region and said polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 linked to a kappa light chain immunoglobulin constant region with a pharmaceutically acceptable carrier.
36. The method of claim 35 wherein the pharmaceutically acceptable carrier includes water, buffer and a sugar.
37. The method of claim 1 wherein said polypeptide is linked to a gamma-1 heavy chain immunoglobulin constant chain.
38. The method of claim 1 wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 45.
39. The method of claim 38 wherein the polypeptide is linked to a gamma-1 heavy chain immunoglobulin constant chain.
40. The method of claim 12 wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 45.
41. The method of claim 40 wherein the polypeptide is linked to a gamma-1 heavy chain immunoglobulin constant chain.
42. The method of claim 17 wherein the polypeptide comprising amino acids 20-137 of SEQ ID NO: 45 comprises the amino acid sequence set forth in SEQ ID NO: 45; and wherein the polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 comprises the amino acid sequence set forth in SEQ ID NO: 78.
43. The method of claim 42 wherein the polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 45 is linked to a gamma-1 heavy chain immunoglobulin constant chain; and wherein the polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 78 is linked to a kappa light chain immunoglobulin constant chain.
44. The method of claim 28 wherein the polypeptide comprising amino acids 20-137 of SEQ ID NO: 45 comprises the amino acid sequence set forth in SEQ ID NO: 45; and wherein the polypeptide comprising amino acids 20-128 of SEQ ID NO: 78 comprises the amino acid sequence set forth in SEQ ID NO: 78.
45. The method of claim 44 wherein the polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 45 is linked to a gamma-1 heavy chain immunoglobulin constant chain; and wherein the polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 78 is linked to a kappa light chain immunoglobulin constant chain.