Antibody therapeutics that bind CD38
View Patent ↗There is disclosed compositions and methods relating to or derived from anti-CD38 antibodies. More specifically, there is disclosed fully human antibodies that bind CD38, CD38-antibody binding fragments and derivatives of such antibodies, and CD38-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease.
1. A recombinant fully human anti-CD38 antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable domain amino acid sequence comprising all of the complementarity determining regions (CDRs) of SEQ ID NO. 3; and comprising a light chain variable domain amino acid sequence comprising all of the CDRs of SEQ ID NO. 4.
2. The recombinant anti-CD38 antibody, or antigen-binding fragment thereof, of claim 1 , which has a K D of at least 1×10 −6 M.
3. The recombinant anti-CD38 antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody is an IgG1 or an IgG4.
4. The recombinant anti-CD38 antibody, or antigen-binding fragment of claim 1 , wherein the antibody, or antigen-binding fragment is a Fab, a Fab′, a F(ab′)2, a Fv, a single-chain antibody (scFv), a chimeric antibody, a diabody, a triabody or a tetrabody.
5. The recombinant anti-CD38 antigen-binding fragment of claim 1 , which is a single chain antibody (scFv).
6. The recombinant fully human anti-CD38 antibody, or an antigen-binding fragment thereof, of claim 1 , wherein said antibody comprises
a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 3; and
a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO. 4.
7. The recombinant fully human anti-CD38 antibody of claim 6 , wherein the antibody has a dissociation constant (K D ) of at least 1×10 −6 M.
8. The recombinant fully human anti-CD38 antibody of claim 6 , wherein the antibody is an IgG1 or an IgG4.
9. The recombinant anti-CD38 antigen-binding fragment of claim 6 , wherein the fragment is a Fab fragment or a single chain antibody (scFv).
10. A pharmaceutical composition comprising the recombinant anti-CD38 antibody, or antigen-binding fragment of claim 1 , and a pharmaceutically acceptable carrier.
11. A method of treating a hematological cancer in a human subject in need thereof, said method comprising the step of administering an effective amount of the recombinant anti-CD38 antibody, or antigen-binding fragment thereof, of claim 1 to the subject, such that the cancer is treated.
12. The method of claim 11 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), multiple myeloma (MM), B chronic lymphocytic leukemia (B-CLL), B and T acute lymphocytic leukemia (ALL), T cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin's Lymphoma (HL), and chronic myeloid leukemia (CML).
13. A method for treating a hematological cancer in a human subject in need thereof, said method comprising the step of administering an effective amount of the recombinant fully human anti-CD38 antibody of claim 6 to the subject, such that the cancer is treated.
14. The method of claim 13 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), multiple myeloma (MM), B chronic lymphocytic leukemia (B-CLL), B and T acute lymphocytic leukemia (ALL), T cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin's Lymphoma (HL), and chronic myeloid leukemia (CML).
15. A recombinant fully human anti-CD38 antibody fragment that binds to CD38, wherein the fragment comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO. 3; and
a light chain variable domain sequence comprising the amino acid sequence of SEQ ID NO. 4.
16. The recombinant fully human anti-CD38 antibody fragment of claim 15 , wherein the antibody fragment is an IgG1 or an IgG4.
17. The recombinant fully human anti-CD38 antibody fragment of claim 15 , wherein the fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, an Fv, and a single-chain antibody.
18. A method for treating a hematological cancer in a human subject in need thereof, said method comprising the step of administering an effective amount of the recombinant fully human anti-CD38 antibody fragment of claim 15 to the subject, such that the cancer is treated.
19. The method of claim 18 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), multiple myeloma (MM), B chronic lymphocytic leukemia (B-CLL), B and T acute lymphocytic leukemia (ALL), T cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin's Lymphoma (HL), and chronic myeloid leukemia (CML).
20. A single chain anti-CD38 antibody comprising a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO. 3, and comprising a light chain variable domain comprising the amino acid sequence of SEQ ID NO. 4, wherein the heavy chain variable domain and the light chain variable domain are connected by a peptide linker.
21. A method of treating a hematological cancer in a human subject in need thereof, said method comprising the step of administering an effective amount of the single chain anti-CD38 antibody of claim 20 to the subject, such that the cancer is treated.
22. The method of claim 21 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), multiple myeloma (MM), B chronic lymphocytic leukemia (B-CLL), B and T acute lymphocytic leukemia (ALL), T cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin's Lymphoma (HL), and chronic myeloid leukemia (CML).