Anti-ox40 antibodies and methods of use thereof

Abstract

The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.

1 - 130 . (canceled) 
     
     
         131 . An antibody that specifically binds human OX40, the antibody comprising: a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 16; and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 15. 
     
     
         132 . The antibody of  claim 131 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 16. 
     
     
         133 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 21. 
     
     
         134 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 23. 
     
     
         135 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 51. 
     
     
         136 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 52. 
     
     
         137 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 60. 
     
     
         138 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 61. 
     
     
         139 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 62. 
     
     
         140 . The antibody of  claim 132 , comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 63. 
     
     
         141 . The antibody of  claim 131 , wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 15. 
     
     
         142 . The antibody of  claim 141 , comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 20. 
     
     
         143 . The antibody of  claim 141 , comprising a light chain comprising the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         144 . The antibody of  claim 131 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 16, and wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 15. 
     
     
         145 . The antibody of  claim 131 , further comprising one or more heavy chain constant regions, one or more light chain constant regions, or both one or more heavy chain constant regions and one or more light chain constant regions. 
     
     
         146 . The antibody of  claim 145 , wherein the heavy chain constant region is selected from the group consisting of human IgG 1 , IgG 2 , IgG 3 , IgG 4 , IgA 1 , and IgA 2 . 
     
     
         147 . The antibody of  claim 146 , wherein the antibody comprises an IgG 1  heavy chain constant region. 
     
     
         148 . The antibody of  claim 147 , wherein the IgG 1  is a non-fucosylated IgG 1 . 
     
     
         149 . The antibody of  claim 147 , wherein the amino acid sequence of the IgG 1  heavy chain constant region comprises a N297A mutation, a N297Q mutation, or a mutation selected from the group consisting of D265A, P329A, and a combination thereof, numbered according to the EU index as in Kabat. 
     
     
         150 . The antibody of  claim 146 , wherein the antibody comprises an IgG 4  heavy chain constant region. 
     
     
         151 . The antibody of  claim 150 , wherein the amino acid sequence of the IgG 4  heavy chain constant region comprises a S228P mutation, numbered according to the EU index as in Kabat. 
     
     
         152 . The antibody of  claim 146 , wherein the antibody comprises an IgG 2  heavy chain constant region. 
     
     
         153 . The antibody of  claim 152 , wherein the amino acid sequence of the IgG 2  heavy chain constant region comprises a C127S mutation, numbered according to the EU index as in Kabat. 
     
     
         154 . The antibody of  claim 146 , wherein the antibody further comprises a human kappa light chain constant region. 
     
     
         155 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 23, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 20. 
     
     
         156 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 51, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 20. 
     
     
         157 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 52, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 20. 
     
     
         158 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 21, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         159 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 23, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         160 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 51, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         161 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 52, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         162 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 60, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         163 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 61, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         164 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 62, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50. 
     
     
         165 . The antibody of  claim 131 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 63, and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO: 50.