Anti-α2 integrin antibodies and their uses
View Patent ↗The invention relates to anti-α2 integrin antibodies and their uses. Humanized antibodies are disclosed that bind to the I domain of α2 integrin and inhibit the interaction of α2β1 integrin with collagen. Also disclosed are therapeutic uses of anti-α2 integrin antibodies in treating α2β1-mediated disorders, including anti-α2 integrin antibodies that bind to α2 integrin without activating platelets.
1. A humanized anti-α2 integrin antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:109.
2. A humanized anti-α2 integrin antibody comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 91.
3. A humanized anti-α2 integrin antibody comprising (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:109; and (b) a light chain variable region comprising the amino acid sequence of SEQ ID NO:91.
4. The humanized anti-α2 integrin antibody of any one of claim 1 , 2 or 3 , wherein the antibody comprises a constant region.
5. The humanized anti-α2 integrin antibody of claim 4 , wherein the constant region is γ1.
6. The humanized anti-α2 integrin antibody of claim 4 , wherein the constant region is γ4.
7. The humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 , wherein the antibody recognizes the I domain of human α2 integrin.
8. The humanized anti-α2 integrin antibody of any one of 1 , 2 or 3 , wherein the antibody binds α2β1 integrin.
9. The humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 , which is a full length antibody.
10. The humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 , which is an antigen-binding fragment.
11. The humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 , bound to a detectable label.
12. The humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 , immobilized on solid phase.
13. The humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 , wherein the antibody inhibits binding of α2 or α2β1 integrin to an α2β1 integrin ligand.
14. The humanized anti-α2 integrin antibody of claim 13 , wherein the α2β1 integrin ligand is selected from collagen, laminin, Echovirus-1, decorin, E-cadherin, matrix metalloproteinase I (MMP-I), endorepellin, collectin and C1q complement protein.
15. A kit comprising the humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 and instructions for its use to detect α2 or α2β1 integrin protein.
16. A composition comprising the humanized anti-α2 integrin antibody of any one of claims 1 , 2 or 3 and a pharmaceutically acceptable carrier.