Anti-CD100 neutralizing neutralizing antibodies and methods of using the same
View Patent ↗Compositions and methods are provided for treating diseases associated with CD100, including certain autoimmune diseases, inflammatory diseases, and cancers. In particular, anti-CD100 monoclonal antibodies have been developed to neutralize CD100.
1. An isolated antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) polypeptide comprising VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences comprising SEQ ID NOs: 6, 7, and 8, respectively, and a light chain variable region (VL) polypeptide comprising VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences comprising SEQ ID NOs: 14, 15, and 16, respectively; wherein said antibody or antigen-binding fragment thereof specifically binds CD100.
2. The isolated antibody or antigen-binding fragment thereof of claim 1 wherein the heavy chain variable region (VH) of said antibody or antigen-binding fragment thereof comprises an amino acid sequence at least 90% identical to SEQ ID NO: 9 or SEQ ID NO: 10.
3. The isolated antibody or antigen-binding fragment thereof of claim 1 wherein the light chain variable region (VL) of said antibody or antigen-binding fragment thereof comprises an amino acid sequence at least 90% identical to SEQ ID NO: 17 or SEQ ID NO: 18.
4. The isolated antibody or antigen-binding fragment thereof of claim 1 wherein the VH and VL of said antibody or antigen-binding fragment thereof comprise amino acid sequences at least 90% identical to SEQ ID NO: 9 and SEQ ID NO: 17, respectively, or SEQ ID NO: 10 and SEQ ID NO: 18, respectively.
5. The isolated antibody or antigen-binding fragment thereof according to claim 4 , wherein the VH and VL of said antibody or antigen-binding fragment thereof comprise amino acid sequences identical to SEQ ID NO: 9 and SEQ ID NO: 17, respectively, or SEQ ID NO: 10 and SEQ ID NO: 18, respectively.
6. The antibody or antigen-binding fragment thereof according to claim 1 which is multispecific.
7. The antibody or antigen-binding fragment thereof according to claim 6 , which is bispecific.
8. The antibody or antigen-binding fragment thereof according to claim 1 which is multivalent and comprises at least two heavy chains and at least two light chains.
9. The antibody or antigen-binding fragment thereof according to claim 1 which binds to human and murine CD100.
10. The antibody or antigen-binding fragment thereof according to claim 1 which specifically binds to a human CD100 polypeptide or fragment thereof with an affinity characterized by a dissociation constant (K D ) of about 5×10 −9 M to about 6×10 −9 M.
11. The antibody or antigen-binding fragment thereof according to claim 1 which inhibits CD100 from binding to a CD100 receptor.
12. The antibody or antigen-binding fragment thereof according to claim 11 , wherein said CD100 receptor is Plexin-B1.
13. The antibody or antigen-binding fragment thereof according to claim 1 further comprising a heterologous polypeptide fused thereto.
14. The antibody or antigen-binding fragment thereof according to claim 1 wherein said antibody or antigen-binding fragment thereof is conjugated to an agent selected from the group consisting of a cytotoxic agent, a therapeutic agent, a cytostatic agent, a biological toxin, a prodrug, a peptide, a protein, an enzyme, a virus, a lipid, a biological response modifier, a pharmaceutical agent, a lymphokine, a heterologous antibody or fragment thereof, a detectable label, polyethylene glycol (PEG), and a combination of two or more of any said agents.
15. The antibody or antigen-binding fragment thereof according to claim 14 , wherein said cytotoxic agent is selected from the group consisting of a radionuclide, a biotoxin, an enzymatically active toxin, or a combination of two or more of any said cytotoxic agents.
16. The antibody or antigen-binding fragment thereof according to claim 14 , wherein said detectable label is selected from the group consisting of an enzyme, a fluorescent label, a chemiluminescent label, a bioluminescent label, a radioactive label, or a combination of two or more of any said detectable labels.
17. A composition comprising the antibody or antigen-binding fragment thereof according to claim 1 and a carrier.
18. A composition of claim 17 , wherein said carrier is selected from the group consisting of saline, buffered saline, dextrose, water, glycerol, and combinations thereof.
19. An antibody or antigen-binding fragment thereof which specifically binds CD100, produced by a method comprising culturing a host cell comprising an isolated VH encoding polynucleotide and an isolated VL encoding polynucleotide, wherein said VH encoding polynucleotide encodes a VH polypeptide comprising VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences consisting of SEQ ID NOs: 6, 7, and 8, respectively; wherein said VL encoding polynucleotide encodes a VL polypeptide comprising VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences consisting of SEQ ID NOs: 14, 15, and 16, respectively; and wherein an antibody or antigen-binding fragment thereof encoded by said VH and VL encoding polynucleotides specifically binds CD100, and recovering said antibody or antigen-binding fragment thereof.