Compositions and Methods for Targeting Connexin Hemichannels

A monoclonal antibody or an antigen-binding fragment thereof, comprising:

• a heavy chain variable domain comprising an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:
• 2;
• and
• a light chain variable domain comprising an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:
• 4;
• wherein the monoclonal antibody or the antigen-binding fragment thereof binds a Cx43 hemichannel and wherein the changes are not in the complementarity determining region.

A pharmaceutical composition comprising:

• a monoclonal antibody or an antigen-binding fragment thereof and a pharmaceutically acceptable carrier, wherein the monoclonal antibody or the antigen-binding fragment thereof comprises:
• a heavy chain variable domain comprising an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:
• 2;
• and
• a light chain variable domain comprising an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:
• 4;
• wherein the monoclonal antibody or the antigen-binding fragment thereof binds a Cx43 hemichannel and wherein the changes are not in the complementarity determining region.

A method of treating a central nervous system inflammatory in a subject, the method comprising administering to the subject an effective amount of an antibody or antigen-binding portion thereof, wherein the antibody or antigen-binding portion thereof, comprises:

• a first, second and third heavy complementarity determining region (CDR) sequence from the heavy chain sequence of SEQ ID NO:
• 2, wherein the first, second and third heavy chain CDR sequences are located at amino acid positions 27-33, 52-56 and 95-102, numbered according to the Kabat numbering system, of the heavy chain amino acid sequence of SEQ ID NO:
• 2, respectively, wherein the antibody or antigen-binding portion thereof, comprises:
• a heavy chain variable domain comprising an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:
• 2;
• and
• a first, second and third light chain CDR sequence from the light chain sequence of SEQ ID NO:
• 4, wherein the first, second and third light chain CDR sequences are located at amino acid positions 27-32, 50-56 and 91-97, numbered according to the Kabat numbering system, of the light chain amino acid sequence of SEQ ID NO:
• 4, respectively wherein the antibody or antigen-binding portion thereof, comprises:
• a light chain variable domain comprising an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:
• 4;
• wherein the antibody or antigen-binding portion thereof binds to a Cx43 hemichannel.