Anti-CD38 antibodies and methods of use
The disclosure provides binding proteins that bind CD38 polypeptides, e.g., human and cynomolgus monkey CD38 polypeptides. For example, the binding proteins can be monospecific, bispecific, or trispecific binding proteins with at least one antigen binding domain that binds a CD38 polypeptide. The disclosure also provides methods for making binding proteins that bind CD38 polypeptides and uses of such binding proteins.
1. A monospecific binding protein that binds a CD38 polypeptide, wherein the monospecific binding protein comprises:
(a) an antibody heavy chain that comprises an antibody heavy chain variable (VH) domain comprising a CDR-H1 sequence comprising the amino acid sequence of GYTFTSYA (SEQ ID NO:37), a CDR-H2 sequence comprising the amino acid sequence of IYPGQGGT (SEQ ID NO:38), and a CDR-H3 sequence comprising the amino acid sequence of ARTGGLRRAYFTY (SEQ ID NO:33);
and
(b) an antibody light chain that comprises an antibody light chain variable (VL) domain comprising a CDR-L1 sequence comprising the amino acid sequence of QSVSSYGQGF (SEQ ID NO:39), a CDR-L2 sequence comprising the amino acid sequence of GAS (SEQ ID NO:40), and a CDR-L3 sequence comprising the amino acid sequence of QQNKEDPWT (SEQ ID NO:36).
2. The monospecific binding protein of claim 1 , wherein the VH domain comprises the sequence, from N-terminus to C-terminus, FR1-CDR-H1-FR2-CDR-H2-FR3-CDR-H3-FR4; wherein FR1 comprises the sequence QVQLVQSGAEVVKPGASVKVSCKAS (SEQ ID NO:86), QVQLVQSGAEVVKSGASVKVSCKAS (SEQ ID NO:87), or QVQLVQSGAEVVKPGASVKMSCKAS (SEQ ID NO:88); wherein FR2 comprises the sequence MHWVKEAPGQRLEWIGY (SEQ ID NO:90) or MHWVKEAPGQGLEWIGY (SEQ ID NO:91); wherein FR3 comprises the sequence NYNQKFQGRATLTADTSASTAYMELSSLRSEDTAVYFC (SEQ ID NO:93) or NYNQKFQGRATLTADTSASTAYMEISSLRSEDTAVYFC (SEQ ID NO:94); and wherein FR4 comprises the sequence WGQGTLVTVSS (SEQ ID NO:96).
3. The monospecific binding protein of claim 1 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO:13, and the VL domain comprises the amino acid sequence of SEQ ID NO:14.
4. The monospecific binding protein of claim 3 , wherein the antibody heavy chain comprises the amino acid sequence of SEQ ID NO:15, and the antibody light chain comprises the amino acid sequence of SEQ ID NO:16.
5. The monospecific binding protein of claim 1 , wherein the monospecific binding protein cross-reacts with an extracellular domain of a human CD38 polypeptide and an extracellular domain of a cynomolgus monkey CD38 polypeptide.
6. The monospecific binding protein of claim 5 , wherein the monospecific binding protein binds a human CD38 polypeptide comprising the amino acid sequence of SEQ ID NO:1.
7. The monospecific binding protein of claim 6 , wherein the monospecific binding protein binds the human CD38 polypeptide comprising the amino acid sequence of SEQ ID NO:1 with an equilibrium dissociation constant (K D ) of 2.1 nM or less.
8. The monospecific binding protein of claim 5 , wherein the monospecific binding protein binds a human isoform E CD38 polypeptide comprising the amino acid sequence of SEQ ID NO:105.
9. The monospecific binding protein of claim 5 , wherein the monospecific binding protein binds a cynomolgus monkey CD38 polypeptide comprising the amino acid sequence of SEQ ID NO:30.
10. The monospecific binding protein of claim 9 , wherein the monospecific binding protein binds the cynomolgus monkey CD38 polypeptide comprising the amino acid sequence of SEQ ID NO:30 with an equilibrium dissociation constant (K D ) of 1.3 nM or less.
11. The monospecific binding protein of claim 1 , wherein the binding protein is a chimeric or humanized antibody.
12. The monospecific binding protein of claim 1 , wherein the binding protein is a monoclonal antibody.
13. The monospecific binding protein of claim 1 , wherein the binding protein comprises two full-length antibody heavy chains comprising an Fc region.
14. The monospecific binding protein of claim 13 , wherein the Fc region is a human Fc region, and wherein the binding protein induces antibody-dependent cellular cytotoxicity of a cell expressing CD38 on its cell surface.
15. The monospecific binding protein of claim 13 , wherein the Fc region is a human IgG1 Fc region.
16. A polynucleotide encoding the monospecific binding protein of claim 1 .
17. A vector comprising the polynucleotide of claim 16 .
18. A host cell comprising the polynucleotide of claim 16 .
19. A method of producing a monospecific binding protein, the method comprising culturing the host cell of claim 18 such that the monospecific binding protein is produced.
20. The method of claim 19 , further comprising recovering the monospecific binding protein from the host cell.
21. A pharmaceutical composition comprising the monospecific binding protein of claim 1 and a pharmaceutically acceptable carrier.
22. The monospecific binding protein of claim 15 , wherein the human IgG1 Fc region comprises one or more residues involved in Fc receptor binding or antibody-dependent cellular cytotoxicity (ADCC) that have been modified from a native human IgG1 Fc sequence.
23. A monospecific, monoclonal antibody that binds a CD38 polypeptide, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:15 and a light chain comprising the amino acid sequence of SEQ ID NO:16.
24. A polynucleotide encoding the antibody of claim 23 .
25. A vector comprising the polynucleotide of claim 24 .
26. A host cell comprising the polynucleotide of claim 24 .
27. A method of producing an antibody, the method comprising culturing the host cell of claim 26 such that the antibody is produced.
28. The method of claim 27 , further comprising recovering the antibody from the host cell.
29. A pharmaceutical composition comprising the antibody of claim 23 and a pharmaceutically acceptable carrier.