Chimeric and humanized antibodies to α5β1 integrin that modulate angiogenesis
View Patent ↗The present invention provides chimeric and humanized antibodies that specifically recognize α5β1 integrin, and methods for using the antibodies for reducing or inhibiting angiogenesis in a tissue. Also provided are methods of determining therapeutically acceptable doses of the antibodies and pharmaceutical compositions including the same.
1. A method of treatment of an angiogenesis-associated ocular disease comprising applying one or more doses of an anti-α5β1 integrin antibody to an injured eye tissue, wherein the anti-α5β1 integrin antibody comprises:
a) a heavy chain variable region consisting of the amino acid sequence of SEQ ID NO:1, a light chain variable region consisting of the amino acid sequence of SEQ ID NO:7, and a constant region, wherein the source of the constant region is a human IgG;
b) a heavy chain consisting of the amino acid sequence of SEQ ID NO: 25 and a light chain consisting of the amino acid sequence of SEQ ID NO: 26;
c) a heavy chain consisting of the amino acid sequence of SEQ ID NO: 28 and a light chain consisting of the amino acid sequence of SEQ ID NO: 26; or
d) a heavy chain consisting of the amino acid sequence of SEQ ID NO: 31 and a light chain consisting of the amino acid sequence of SEQ ID NO: 32.
2. The method of claim 1 , wherein the anti-a5f31 integrin antibody exhibits inhibition of subretinal hemorrhage in rabbit eye due to a VEGF/bFGF hydrogel polymer implant pellet.
3. The method of claim 2 , wherein the angiogenesis-associated ocular disease is macular degeneration.
4. The method of claim 1 wherein the ocular disease is selected from the group consisting of macular degeneration, diabetic retinopathy, and choroidal neovascularization.
5. The method of claim 1 wherein applying comprises intravitreal injection.
6. The method of claim 1 wherein applying comprises intravenous injection.
7. The method of claim 1 , wherein the anti-α5β1 integrin antibody comprises a heavy chain variable region consisting of the amino acid sequence of SEQ ID NO: 1, a light chain variable region consisting of the amino acid sequence of SEQ ID NO:7, and a constant region, wherein the source of the constant region is a human IgG.
8. The method of claim 1 , wherein the anti-α5β1 integrin antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 25 and a light chain consisting of the amino acid sequence of SEQ ID NO: 26.
9. The method of claim 1 , wherein the anti-α5β1 integrin antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 28 and a light chain consisting of the amino acid sequence of SEQ ID NO: 26.
10. The method of claim 1 , wherein the anti-α5β1 integrin antibody comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 31 and a light chain consisting of the amino acid sequence of SEQ ID NO: 32.