Anti-BCMA heavy chain-only antibodies
Anti-BCMA heavy chain-only antibodies (HCAb) and disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat B-cell disorders characterized by the expression of BCMA.
1. A heavy chain-only antibody binding to human B-Cell Maturation Antigen (BCMA) comprising a heavy chain variable region comprising:
(a) a CDR1 sequence comprising SEQ ID NO: 1, a CDR2 sequence comprising SEQ ID NO: 5, and a CDR3 sequence comprising SEQ ID NO: 19; or
(b) a CDR1 sequence comprising SEQ ID NO: 2, a CDR2 sequence comprising SEQ ID NO: 54, and a CDR3 sequence comprising SEQ ID NO: 19;
in a human VH framework.
2. The heavy chain-only antibody of claim 1 , further comprising a heavy chain constant region sequence in the absence of a CH1 sequence.
3. The heavy chain-only antibody of claim 1 , which is in a CAR-T format.
4. The heavy chain-only antibody of claim 1 , which is present in a CAR-transduced T-cell.
5. A pharmaceutical composition comprising the heavy chain-only antibody of claim 1 .
6. The heavy chain-only antibody of claim 1 , wherein the heavy chain variable region comprises a CDR1 sequence comprising SEQ ID NO: 1, a CDR2 sequence comprising SEQ ID NO: 5, and a CDR3 sequence comprising SEQ ID NO: 19, in a human VH framework.
7. The heavy chain-only antibody of claim 6 , wherein the heavy chain variable region has at least 95% sequence identity to SEQ ID NO: 20.
8. The heavy chain-only antibody of claim 7 , wherein the heavy chain variable region comprises SEQ ID NO: 20.
9. The heavy chain-only antibody of claim 6 , further comprising a heavy chain constant region sequence in the absence of a CH1 sequence.
10. The heavy chain-only antibody of claim 6 , which is in a CAR-T format.
11. The heavy chain-only antibody of claim 6 , which is present in a CAR-transduced T-cell.
12. The heavy chain-only antibody of claim 1 , wherein the heavy chain variable region comprises a CDR1 sequence comprising SEQ ID NO: 2, a CDR2 sequence comprising SEQ ID NO: 54, and a CDR3 sequence comprising SEQ ID NO: 19, in a human VH framework.
13. The heavy chain-only antibody of claim 12 , wherein the heavy chain variable region has at least 95% sequence identity to SEQ ID NO: 21.
14. The heavy chain-only antibody of claim 13 , wherein the heavy chain variable region comprises SEQ ID NO: 21.
15. The heavy chain-only antibody of claim 12 , further comprising a heavy chain constant region sequence in the absence of a CH1 sequence.
16. The heavy chain-only antibody of claim 12 , which is in a CAR-T format.
17. The heavy chain-only antibody of claim 12 , which is present in a CAR-transduced T-cell.