ANG-2/VEGF ANTIBODIES AND USES THEREOF
Described herein are antibodies that bind VEGF_A or ANG-2, or bispecific antibodies that bind VEGF_A and ANG-2. Antibodies of this disclosure are useful for treating diseases of the eye including macular degeneration.
1 .- 117 . (canceled)
118 . A vascular endothelial growth factor A (VEGF-A) binding antibody or antigen binding fragment thereof comprising:
a. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 3 (GYTFSIYT);
b. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 4 (INPYNGNT); and
c. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 5 (AKAPAVFWWTGLDY);
wherein the antibody or antigen binding fragment thereof binds to VEGF-A.
119 . The antibody or antigen binding fragment thereof of claim 118 , comprising a heavy chain variable region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 1.
120 . The antibody or antigen binding fragment thereof of claim 118 , comprising a heavy chain constant region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 2.
121 . The antibody or antigen binding fragment thereof of claim 118 , further comprising a surrogate light chain, and wherein the surrogate light chain comprises:
a. a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 23 (NDHDIGVYS);
b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 24 (YFSQSDK); and
c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 25 (AMGARSSVTH).
122 . A nucleic acid or plurality of nucleic acids encoding the antibody or antigen binding fragment thereof of claim 118 .
123 . A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 118 and a pharmaceutically acceptable carrier, excipient, or diluent.
124 . A method of treating a disease of an eye in an individual comprising administering to the antibody or antigen binding fragment thereof of claim 118 , thereby treating the disease of the eye.
125 . An angiopoietin 2 (ANG-2) binding antibody or antigen binding fragment thereof comprising:
a. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 13 (GFTFSSYG);
b. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 14 (ISADSGDK); and
c. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 15 (AKEFISWIYTFDYLDY),
wherein the antibody or antigen binding fragment thereof binds to ANG-2.
126 . The antibody or antigen binding fragment thereof of claim 125 , comprising a heavy chain variable region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 11.
127 . The antibody or antigen binding fragment thereof of claim 125 , comprising a heavy chain constant region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 12.
128 . The antibody or antigen binding fragment thereof of claim 125 , further comprising a surrogate light chain, and wherein the surrogate light chain comprises:
a. a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 23 (NDHDIGVYS);
b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 24 (YFSQSDK); and
c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 25 (AMGARSSVTH).
129 . A nucleic acid or plurality of nucleic acids encoding the antibody or antigen binding fragment thereof of claim 125 .
130 . A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 125 and a pharmaceutically acceptable carrier, excipient, or diluent.
131 . A method of treating a disease of an eye in an individual comprising administering to the antibody or antigen binding fragment thereof of claim 125 , thereby treating the disease of the eye.
132 . A multispecific antibody comprising:
a vascular endothelial growth factor A (VEGF-A) binding moiety comprising:
a. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 3 (GYTFSIYT);
b. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 4 (INPYNGNT); and
c. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 5 (AKAPAVFWWTGLDY); and
an angiopoietin 2 (ANG-2) binding moiety, wherein the multispecific antibody binds to VEGF-A and ANG-2.
133 . The multispecific antibody of claim 132 , wherein the ANG-2 binding moiety comprises:
a. a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 13 (GFTFSSYG);
b. a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 14 (ISADSGDK); and
c. a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 15 (AKEFISWIYTFDYLDY).
134 . The multispecific antibody of claim 132 , wherein the VEGF-A binding moiety comprises a heavy chain variable region comprising an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 1.
135 . The multispecific antibody of claim 132 , wherein the VEGF-A binding moiety comprises a heavy chain constant region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 2.
136 . The multispecific antibody of claim 132 , wherein the ANG-2 binding moiety comprises a heavy chain variable region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 11.
137 . The multispecific antibody of claim 132 , wherein the ANG-2 binding moiety comprises a heavy chain constant region comprising an amino acid sequence comprising at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence set forth in SEQ ID NO: 12.
138 . The multispecific antibody of claim 132 , further comprising a surrogate light chain, and wherein the surrogate light chain comprises:
a. a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 23 (NDHDIGVYS);
b. a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 24 (YFSQSDK); and
c. a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 25 (AMGARSSVTH).
139 . A nucleic acid or plurality of nucleic acids encoding the multispecific antibody of claim 132 .
140 . A pharmaceutical composition comprising the multispecific antibody of claim 132 and a pharmaceutically acceptable carrier, excipient, or diluent.
141 . A method of treating a disease of an eye in an individual comprising administering to the individual the multispecific antibody of claim 132 , thereby treating the disease of the eye.