Anti-CD38 binding domains

1. A composition comprising an anti-CD38 antigen binding domain comprising:

a) a variable heavy domain (VH) comprising:

i) a VHCDR1 comprising the sequence of SEQ ID NO:2;

ii) a VHCDR2 comprising the sequence of SEQ ID NO:3; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO:4; and

b) a variable light domain (VL) comprising:

i) a VLCDR1 comprising the sequence of SEQ ID NO:6;

ii) a VLCDR2 comprising the sequence of SEQ ID NO:7; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO:8,

wherein the anti-CD38 antigen binding domain is not fused to a Shiga toxin A subunit.

2. A composition according to claim 1 wherein said VH comprises the sequence of SEQ ID NO:1 and said VL comprises the sequence of SEQ ID NO:25.

3. A composition according to claim 1 wherein said VH comprises the sequence of SEQ ID NO:1 and said VL comprises the sequence of SEQ ID NO:5.

4. A composition according to claim 1 wherein said VH and said VL are in a single polypeptide.

5. A composition according to claim 4 wherein said polypeptide comprises a scFv linker and said polypeptide has the orientation from N- to C-terminal of VH-scFv linker-VL.

6. A 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.

7. A composition according to claim 1 wherein the composition comprises a first polypeptide comprising said VH and a second polypeptide comprising said VL.

8. 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.

9. A composition according to claim 8 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.

10. A composition according to claim 9 wherein said heavy constant domain is the heavy constant domain of human IgG1.

11. A composition according to claim 9 wherein said heavy constant domain is a variant of the heavy constant domain of human IgG1.

12. A composition according to claim 11 wherein said variant heavy constant domain of human IgG1 has ablated FcγR binding.

13. A composition according to claim 9 wherein said heavy constant domain is a variant of the heavy constant domain of human IgG4 comprising a S228P amino acid substitution compared to the wild-type heavy constant domain of human IgG4.

14. 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.

15. An expression vector composition comprising:

a) a first expression vector comprising said first nucleic acid of claim 14 ; and

b) a second expression vector comprising said second nucleic acid of claim 14 .

16. A host cell comprising said expression vector composition according to claim 15 .

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 composition comprising an anti-CD38 antigen binding domain comprising:

a) a variable heavy domain (VH) comprising:

i) a VHCDR1 comprising the sequence of SEQ ID NO:10;

ii) a VHCDR2 comprising the sequence of SEQ ID NO:11; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO:12; and

b) a variable light domain (VL) comprising:

i) a VLCDR1 comprising the sequence of SEQ ID NO:14;

ii) a VLCDR2 comprising the sequence of SEQ ID NO:15; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO:16.

20. A composition comprising an anti-CD38 antigen binding domain comprising:

a) a variable heavy domain (VH) comprising:

i) a VHCDR1 comprising the sequence of SEQ ID NO:18;

ii) a VHCDR2 comprising the sequence of SEQ ID NO:19; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO:20; and

b) a variable light domain (VL) comprising:

i) a VLCDRI comprising the sequence of SEQ ID NO:22;

ii) a VLCDR2 comprising the sequence of SEQ ID NO:23; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO:24.

21. A composition comprising an anti-CD38 antigen binding domain comprising:

a) a variable heavy domain (VH) comprising:

i) a VHCDRI comprising the sequence of SEQ ID NO:54;

ii) a VHCDR2 comprising the sequence of SEQ ID NO:55; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO:56; and

b) a variable light domain (VL) comprising:

i) a VLCDRI comprising the sequence of SEQ ID NO:58;

ii) a VLCDR2 comprising the sequence of SEQ ID NO:59; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO:60.