Compositions and methods for antibodies targeting epo

Abstract

The present invention relates to compositions and methods for the inhibition of EPO. The invention provides antibodies and antigen binding fragments thereof that bind to EPO and are able to inhibit EPO-dependent cell proliferation and/or EPO-dependent cell signaling.

1 - 38 . (canceled) 
     
     
         39 . A method of treating diabetic macular edema comprising administering to a subject in need thereof an effective amount of a composition comprising an antibody, or an antigen binding fragment thereof, that binds erythropoietin (EPO), wherein the antibody or antigen binding fragment thereof comprises:
 a) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 1, 2, and 3, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 4, 5, and 6, respectively;   b) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 21, 22, and 23, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 24, 25, and 26, respectively;   c) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 41, 42, and 43, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 44, 45, and 46, respectively; or   d) heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 61, 62, and 63, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 64, 65, and 66, respectively.   
     
     
         40 . The method of  claim 39 , wherein the antibody or antigen binding fragment thereof comprises heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 1, 2, and 3, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 4, 5, and 6, respectively, and wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising amino acid sequence with at least 90% identity to SEQ ID NOs: 13 and 14, respectively. 
     
     
         41 . The method of  claim 40 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain and a light chain with an amino acid sequence set forth in SEQ ID NOs: 15 and 16, respectively. 
     
     
         42 . The method of  claim 39 , wherein the antibody or antigen binding fragment thereof comprises heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 21, 22, and 23, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 24, 25, and 26, respectively, and wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising amino acid sequence with at least 90% identity to SEQ ID NOs: 33 and 34, respectively. 
     
     
         43 . The method of  claim 42 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain and a light chain with an amino acid sequence set forth in SEQ ID NOs: 35 and 36, respectively. 
     
     
         44 . The method of  claim 39 , wherein the antibody or antigen binding fragment thereof comprises heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 41, 42, and 43, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 44, 45, and 46, respectively, and wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising amino acid sequence with at least 90% identity to SEQ ID NOs: 53 and 54, respectively. 
     
     
         45 . The method of  claim 44 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain and a light chain with an amino acid sequence set forth in SEQ ID NOs: 55 and 56, respectively. 
     
     
         46 . The method of  claim 39 , wherein the antibody or antigen binding fragment thereof comprises heavy chain variable region HCDR1, HCDR2, and HCDR3 as set forth in SEQ ID NOs: 61, 62, and 63, respectively, and light chain variable region LCDR1, LCDR2, and LCDR3 as set forth in SEQ ID NOs: 64, 65, and 66, respectively, and wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region comprising amino acid sequence with at least 90% identity to SEQ ID NOs: 73 and 74, respectively. 
     
     
         47 . The method of  claim 46 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain and a light chain with an amino acid sequence set forth in SEQ ID NOs: 75 and 76, respectively. 
     
     
         48 . The method of  claim 39 , wherein the antibody or antigen binding fragment thereof is selected from the group consisting of a human antibody, a chimeric antibody, a monoclonal antibody, a single chain antibody, a Fab, a Fab′, a F(ab′)2, a Fv, and a scFv. 
     
     
         49 . The method of  claim 48 , wherein the antibody or antigen binding fragment is a Fab. 
     
     
         50 . The method of  claim 49 , wherein the composition is administered intravitreally. 
     
     
         51 . The method of  claim 50 , wherein the composition is administered intravitreally from 0.1 mg/eye to 10 mg/eye in the subject. 
     
     
         52 . The method of  claim 51 , wherein the composition is administered intravitreally to the subject in a range selected from the group consisting of 1 mg/eye to 9 mg/eye, 2 mg/eye to 8 mg/eye, 3 mg/eye to 7 mg/eye, 4 mg/eye to 6 mg/eye, and 4.5 mg/eye to 5.5 mg/eye. 
     
     
         53 . The method of  claim 51 , wherein the composition is administered intravitreally to the subject at a dose selected from the group consisting of 0.1 mg/eye, 0.2 mg/eye, 0.3 mg/eye, 0.4 mg/eye, 0.5 mg/eye, 0.6 mg/eye, 0.7 mg/eye, 0.8 mg/eye, 0.9 mg/eye, 1 mg/eye, 2 mg/eye, 3 mg/eye, 4 mg/eye, and 5 mg/eye. 
     
     
         54 . The method of  claim 51 , wherein the composition is administered intravitreally to the subject at 5 mg/eye. 
     
     
         55 . The method of  claim 39 , wherein the method further comprises administering to the subject an anti-vascular endothelial growth factor (VEGF) antibody or an anti-VEGF receptor antibody. 
     
     
         56 . The method of  claim 55 , wherein the anti-VEGF antibody is ranibizumab. 
     
     
         57 . The method of  claim 55 , wherein the anti-VEGF antibody is bevicizumab. 
     
     
         58 . The method of  claim 39 , wherein the method further comprises administering to the subject aflibercept.