Humanized C-kit antibody
This invention relates to compositions and methods for treating c-Kit associated disorders such as fibrosis, and more particularly, to compositions containing humanized c-Kit antibodies.
1. An isolated aglycosylated IgG1 antibody or fragment thereof, wherein said antibody or fragment (i) specifically binds c-Kit, (ii) comprises six CDRs, and (iii) one of said CDRs comprises amino acids 43 to 58 of SEQ ID NO: 2, another of said CDRs comprises amino acids 74 to 80 of SEQ ID NO: 2, another of said CDRs comprises amino acids 113 to 121 of SEQ ID NO: 2, another of said CDRs comprises amino acids 50 to 54 of SEQ ID NO: 4, another of said CDRs comprises amino acids 69 to 85 of SEQ ID NO: 4, and another of said CDRs comprises amino acids 118 to 125 of SEQ ID NO: 4.
2. The antibody or fragment of claim 1 , comprising an amino acid sequence 95% or more identical to the variable region amino acid sequence set forth in SEQ ID NO: 2.
3. The antibody or fragment of claim 1 , comprising an amino acid sequence 98% or more identical to the variable region amino acid sequence set forth in SEQ ID NO: 2.
4. The antibody or fragment of claim 1 comprising amino acids 20 through 465 of the amino acid sequence of SEQ ID NO: 4.
5. The antibody or fragment of claim 1 that comprises an amino acid sequence 95% or more identical to the variable region amino acid sequence set forth in SEQ ID NO: 4.
6. The antibody or fragment of claim 1 that comprises an amino acid sequence 98% or more identical to the variable region amino acid sequence set forth in SEQ ID NO: 4.
7. The antibody or fragment of claim 1 comprising amino acids 21 through 238 of the amino acid sequence of SEQ ID NO: 2.
8. The antibody or fragment of claim 1 that exhibits an avidity kd for c-Kit of lower than 10 −4 , as determined by surface plasmon resonance analysis.
9. A pharmaceutical composition comprising a therapeutically effective amount of an antibody or fragment of claim 1 .
10. The antibody or fragment of claim 1 , wherein said antibody is a monoclonal antibody or fragment thereof.
11. The antibody or fragment of claim 10 , wherein an N-linked glycosylation consensus site at position 297 (Kabat numbering) has been removed.
12. The antibody or fragment of claim 11 , wherein said N-linked glycosylation consensus site was removed by mutating position 297 from asparagine to a different amino acid.
13. The antibody or fragment of claim 8 that exhibits an avidity kd for c-Kit of lower than 10 −6 , as determined by surface plasmon resonance analysis.
14. The antibody or fragment of claim 13 that exhibits an avidity kd for c-Kit of lower than 10 −8 , as determined by surface plasmon resonance analysis.
15. The antibody or fragment of claim 14 that exhibits an avidity kd for c-Kit of lower than 10 −9 , as determined by surface plasmon resonance analysis.