Nucleic acid molecules encoding bispecific anti-BCMA x anti-CD3 antibodies
B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides novel bispecific antibodies (bsAbs) that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing tumor cells. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing BCMA. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced BCMA-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma.
1. A group of nucleic acid molecules encoding a bispecific antigen-binding molecule that binds human B cell maturation antigen (BCMA) and human CD3, wherein the group of nucleic acid molecules comprises:
(a) a first nucleic acid molecule encoding a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 66, wherein the first nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 65;
(b) a second nucleic acid molecule encoding a HCVR comprising the amino acid sequence of SEQ ID NO: 90, wherein the second nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 89; and
(c) a third nucleic acid molecule encoding a common light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 82, wherein the third nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 81.
2. The group of nucleic acid molecules of claim 1 , wherein the bispecific antigen-binding molecule is a bispecific antibody, the first nucleic acid molecule encodes a first heavy, the second nucleic acid molecule encodes a second heavy chain, and the third nucleic acid molecule encodes a common light chain.
3. The group of nucleic acid molecules of claim 2 , wherein the first heavy chain, the second heavy chain, or both the first and second heavy chains comprise a human IgG heavy chain constant region.
4. The group of nucleic acid molecules of claim 3 , wherein the first heavy chain, the second heavy chain, or both the first and second heavy chains comprise a human IgG1 heavy chain constant region.
5. The group of nucleic acid molecules of claim 3 , wherein the first heavy chain, the second heavy chain, or both the first and second heavy chains comprise a human IgG4 heavy chain constant region.
6. A group of nucleic acid molecules encoding a bispecific antigen-binding molecule that binds human BCMA and human CD3, wherein the group of nucleic acid molecules comprises:
(a) a first nucleic acid molecule encoding a HCVR comprising the amino acid sequence of SEQ ID NO: 66, wherein the first nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 65;
(b) a second nucleic acid molecule encoding a HCVR comprising the amino acid sequence of SEQ ID NO: 98, wherein the second nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 97; and
(c) a third nucleic acid molecule encoding a common LCVR comprising the amino acid sequence of SEQ ID NO: 82, wherein the third nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 81.
7. The group of nucleic acid molecules of claim 3 , wherein the bispecific antigen-binding molecule is a bispecific antibody, the first nucleic acid molecule encodes a first heavy, the second nucleic acid molecule encodes a second heavy chain, and the third nucleic acid molecule encodes a common light chain.
8. The group of nucleic acid molecules of claim 7 , wherein the first heavy chain, the second heavy chain, or both the first and second heavy chains comprise a human IgG heavy chain constant region.
9. The group of nucleic acid molecules of claim 8 , wherein the first heavy chain, the second heavy chain, or both the first and second heavy chains comprise a human IgG1 heavy chain constant region.
10. The group of nucleic acid molecules of claim 8 , wherein the first heavy chain, the second heavy chain, or both the first and second heavy chains comprise a human IgG4 heavy chain constant region.
11. An expression vector comprising the group of nucleic acid molecules of claim 1 .
12. A host cell comprising the expression vector of claim 11 .
13. An isolated host cell comprising the group of nucleic acid molecules of claim 1 .
14. A group of expression vectors comprising, respectively, the group of nucleic acid molecules of claim 1 .
15. A host cell comprising the group of expression vectors of claim 14 .
16. An expression vector comprising the group of nucleic acid molecules of claim 6 .
17. A host cell comprising the expression vector of claim 16 .
18. An isolated host cell comprising the group of nucleic acid molecules of claim 6 .
19. A group of expression vectors comprising, respectively, the group of nucleic acid molecules of claim 6 .
20. A host cell comprising the group of expression vectors of claim 19 .