Anti-CD38 binding domains
Provided in this disclosure are anti-CD38 binding domains, a composition comprising the anti-CD38 binding domains, nucleic acids encoding the anti-CD38 binding domains, and a method of using the anti-CD38 binding domains or the composition for treating multiple myeloma.
1. A composition comprising an anti-CD38-antigen binding domain that comprises a variable heavy domain (VH) comprising the sequence of SEQ ID NO: 9 and a variable light domain (VL) comprising the sequence of SEQ ID NO:13.
2. A composition comprising an anti-CD38-antigen binding domain that comprises a VH comprising the sequence of SEQ ID NO:17 and a VL comprising the sequence of SEQ ID NO:21.
3. A composition comprising an anti-CD38-antigen binding domain that comprises a VH comprising the sequence of SEQ ID NO: 53 and a VL comprising the sequence of SEQ ID NO: 57.
4. The composition according to claim 1 , wherein said VH and said VL are in a single polypeptide.
5. The composition according to claim 4 wherein, said polypeptide comprises a scFv linker and said polypeptide has the orientation from N- to C-terminal of VL-scFv linker-VH.
6. A composition according to claim 1 , wherein said composition is an antibody comprising:
a) a heavy chain comprising said VH; and
b) a light chain comprising said VL.
7. The composition according to claim 6 , wherein said heavy chain comprises said variable heavy domain and a heavy constant domain selected from the group consisting of the heavy constant domains of human IgG1, IgG2 and IgG4, or variants thereof.
8. The composition according to claim 7 , wherein said heavy constant domain is the heavy constant domain of human IgG1.
9. The composition according to claim 8 , wherein said heavy constant domain is a variant of the heavy constant domain of human IgG1.
10. The composition according to claim 9 , wherein said variant heavy constant domain of human IgG1 has ablated FcγR binding.
11. A nucleic acid composition encoding said composition according to claim 7 , wherein said nucleic acid composition comprises:
a) a first nucleic acid encoding said first polypeptide; and
b) a second nucleic acid encoding said second polypeptide.
12. A nucleic acid composition comprising a nucleic acid encoding said composition according to claim 4 .
13. An expression vector composition comprising said nucleic acid of claim 12 .
14. An expression vector composition comprising said first and second nucleic acids of claim 11 .
15. An expression vector composition comprising:
a) a first expression vector comprising said first nucleic acid of claim 11 ; and
b) a second expression vector comprising said second nucleic acid of claim 11 .
16. A host cell comprising said expression vector composition according to claim 13 .
17. A method of making a composition comprising an anti-CD38 antigen binding domain, comprising culturing said host cell of claim 16 under conditions wherein said composition comprising the anti-CD38 binding domain is expressed, and recovering said composition.
18. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of said composition according to claim 1 .
19. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of said composition according to claim 2 .
20. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of said composition according to claim 3 .