Antibodies capable of blocking the interaction between CD48 and a CD48 receptor
The present invention provides antibodies that bind to CD48 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human CD48. In certain embodiments, the antibodies of the present invention block the binding of CD48 to one or more CD48 receptor. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more CD48 biological activities, including the treatment of allergic conditions and other inflammatory conditions.
1. An isolated antibody, or antigen-binding fragment thereof, that specifically binds human CD48 (SEQ ID NO:384) and blocks the interaction between human CD48 and a CD48 receptor with an IC 50 of less than about 400 pM in a CD48/CD48 receptor binding assay and comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO:368 and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:370, wherein the CD48 receptor is human CD2 (SEQ ID NO:392) or human 2B4 (SEQ ID NO:390), and wherein the antibody or antigen-binding fragment binds an epitope within Ig domain 1 of human CD48 (amino acids 29 to 127 of SEQ ID NO:384).
2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within amino acids 60 to 125 of SEQ ID NO:384.
3. The antibody or antigen-binding fragment of claim 2 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within amino acids 60 to 68 of SEQ ID NO:384 and/or amino acids 107 to 125 of SEQ ID NO:384.
4. The antibody or antigen-binding fragment of claim 3 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within amino acids 60 to 68 of SEQ ID NO:384 and with one or more amino acids located within amino acids 107 to 125 of SEQ ID NO:384.
5. The antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment comprises heavy and light chain CDRs having the amino acid sequences of SEQ ID NOs: 354, 356, 358, 362, 364 and 366.
6. The antibody or antigen-binding fragment of claim 5 , wherein the antibody or antigen-binding fragment comprises an HCVR having the amino acid sequence of SEQ ID NO:368, and an LCVR having the amino acid sequence of SEQ ID NO:370.
7. The isolated antibody, or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof inhibits activation of primary human peripheral blood mononuclear cells (PBMCs) in vitro.
8. The antibody or antigen-binding fragment of claim 7 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within amino acids 60 to 125 of SEQ ID NO:384.
9. The antibody or antigen-binding fragment of claim 8 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within amino acids 60 to 68 of SEQ ID NO:384 and/or amino acids 107 to 125 of SEQ ID NO:384.
10. The antibody or antigen-binding fragment of claim 9 , wherein the antibody or antigen-binding fragment interacts with one or more amino acids located within amino acids 60 to 68 of SEQ ID NO:384 and with one or more amino acids located within amino acids 107 to 125 of SEQ ID NO:384.
11. The antibody or antigen-binding fragment of claim 10 , wherein the antibody or antigen-binding fragment comprises the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO:368 and the CDRs of a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:370.
12. The antibody or antigen-binding fragment of claim 11 , wherein the antibody or antigen-binding fragment comprises heavy and light chain CDRs having the amino acid sequences of SEQ ID NOs: 354, 356, 358, 362, 364 and 366.
13. The antibody or antigen-binding fragment of claim 12 , wherein the antibody or antigen-binding fragment comprises an HCVR having the amino acid sequence of SEQ ID NO:368, and an LCVR having the amino acid sequence of SEQ ID NO:370.
14. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 300 pM in a CD48/2B4 binding assay.
15. The antibody or antigen-binding fragment of claim 14 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 200 pM in a CD48/2B4 binding assay.
16. The antibody or antigen-binding fragment of claim 15 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 100 pM in a CD48/2B4 binding assay.
17. The antibody or antigen-binding fragment of claim 16 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 60 pM in a CD48/2B4 binding assay.
18. The antibody or antigen-binding fragment of claim 7 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 300 pM in a CD48/2B4 binding assay.
19. The antibody or antigen-binding fragment of claim 18 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 200 pM in a CD48/2B4 binding assay.
20. The antibody or antigen-binding fragment of claim 19 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 100 pM in a CD48/2B4 binding assay.
21. The antibody or antigen-binding fragment of claim 20 , wherein the antibody or antigen-binding fragment thereof blocks the interaction between human CD48 and human 2B4 with an IC 50 of less than about 60 pM in a CD48/2B4 binding assay.