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 a chimeric or humanized anti-α5β1 integrin antibody to an eye, wherein the anti-α5β1 integrin antibody comprises a heavy chain variable region selected from the group consisting of the amino acid sequences of SEQ ID NOs:25, 28, and 31, a light chain variable region consisting of the amino acid sequences of SEQ ID NOs:26 and 32, and a human IgG constant region.
2. The method of claim 1 , wherein the source of the constant region is human IgG4 or IgG2.
3. The method of claim 1 , wherein the ocular disease is selected from the group consisting of macular degeneration, diabetic retinopathy, or choroidal neovascularization.
4. The method of claim 1 , wherein the anti-α5β1 integrin antibody comprises:
a) a heavy chain variable region consisting of the amino acid sequence of SEQ ID NO:25 and a light chain variable region consisting of the amino acid sequence of SEQ ID NO:26;
b) a heavy chain variable region consisting of the amino acid sequence of SEQ ID NO:28 and a light chain variable region consisting of the amino acid sequence of SEQ ID NO:26; or,
c) a heavy chain variable region consisting of the amino acid sequence of SEQ ID NO:31 and a light chain variable region consisting of the amino acid sequence of SEQ ID NO:32.
5. The method of claim 1 , wherein applying comprises intravitreal injection.
6. The method of claim 1 , wherein applying comprises intravenous injection.