Anti-CD47 antibody molecules
The invention relates to antibody molecules and antigen-binding portions thereof which bind specifically to CD47 (Cluster of Differentiation 47, also known as integrin associated protein [IAP]). In aspects of the invention, the anti-CD47 antibody molecules and antigen-binding portions thereof specifically bind to human CD47 and cynomolgus monkey CD47. Medical uses of the anti-CD47 antibody molecules and antigen-binding portions of the invention are disclosed. The anti-CD47 antibody molecules and antigen-binding portions of the invention represent modified and optimised binding molecules compared with a VxP037 murine/humanized anti-CD47 antibody described in WO2014/093678A2.
1. An antibody molecule that specifically binds to human Integrin Associated Protein (CD47) and cynomolgus monkey CD47, or an antigen-binding portion thereof, wherein the antibody molecule or antigen-binding portion comprises:
(a) a heavy chain variable region comprising a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 49, a HCDR2 of SEQ ID NO: 50, and a HDCR3 of SEQ ID NO: 51; and a light chain variable region comprising a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 52, a LCDR2 of SEQ ID NO: 53, and a LDCR3 of SEQ ID NO: 54; or
(b) a heavy chain variable region comprising a HCDR1 of SEQ ID NO: 49, a HCDR2 of SEQ ID NO: 50, and a HDCR3 of SEQ ID NO: 51; and a light chain variable region comprising a LCDR1 of SEQ ID NO: 52, a LCDR2 of SEQ ID NO: 85, and a LDCR3 of SEQ ID NO: 54.
2. The antibody molecule or antigen-binding portion of claim 1 , wherein the antibody molecule or antigen-binding portion is humanized or chimeric.
3. The antibody molecule or antigen-binding portion of claim 1 , wherein the heavy chain variable region, the light chain variable region, or both the heavy chain variable region and the light chain variable region comprise a human variable domain framework scaffold into which the CDRs have been inserted.
4. The antibody molecule or antigen-binding portion of claim 1 , wherein the heavy chain variable region comprises an IGHV5-51 human germline scaffold into which the HCDR1, HCDR2 and HCDR3 sequences have been inserted.
5. The antibody molecule or antigen-binding portion of claim 1 , wherein the light chain variable region comprises an IGKV2-28 human germline scaffold into which the LCDR1, LCDR2 and LCDR3 sequences have been inserted.
6. The antibody molecule or antigen-binding portion of claim 1 , wherein the antibody molecule or antigen-binding portion comprises an immunologically inert constant region.
7. The antibody molecule or antigen-binding portion of claim 1 , wherein the antibody molecule or antigen-binding portion is a Fab fragment, a F(ab) 2 fragment, an Fv fragment, a tetrameric antibody, a tetravalent antibody, a multispecific antibody or an scFv.
8. The antibody molecule or antigen-binding portion of claim 7 , wherein the multispecific antibody is a bivalent antibody.
9. The antibody molecule or antigen-binding portion of claim 1 , wherein the antibody molecule or antigen-binding portion specifically binds to mouse CD47.
10. A pharmaceutical composition comprising the antibody molecule or antigen-binding portion of claim 1 and a pharmaceutically acceptable excipient, carrier, buffer or stabilizer.