Modified anti-PD-L1 antibody and methods and uses for treating a neurodegenerative disease
The present specification discloses modified anti-PD-L1 antibodies that abolishes Fc-related effector function and enhances clearance rate while maintaining therapeutic efficacy for neurodegenerative disease modification. The present specification also discloses nucleic acid sequences and expression constructs encoding such modified anti-PD-L1 antibodies as well as methods of making such modified anti-PD-L1 antibodies. In addition, the present specification discloses methods of treatment and uses that employ an administration regime of the disclosed anti-PD-L1 antibodies that ensures the antibodies are present for only a specific period of time and then are sufficiently cleared from the body to ensure treatment efficacy is maintained.
1. A modified anti-Programmed Death Ligand 1 (PD-L1) antibody, comprising
a heavy chain comprising a heavy chain variable region including a CDR1 of SEQ ID NO: 3 or SEQ ID NO: 4, a CDR2 of SEQ ID NO: 5 or SEQ ID NO: 6, and a CDR3 of SEQ ID NO: 7 or SEQ ID NO: 8, and a heavy chain constant region of SEQ ID NO: 55; SEQ ID NO: 56 or SEQ ID NO: 57 and
a light chain comprising a light chain variable region including CDR1 of SEQ ID NO: 10 or SEQ ID NO: 11, a CDR2 of SEQ ID NO: 12 or SEQ ID NO: 13 and a CDR3 of SEQ ID NO: 14 or SEQ ID NO 15.
2. The modified anti-PD-L1 antibody according to claim 1 , wherein the heavy chain variable region is SEQ ID NO: 2.
3. The modified anti-PD-L1 antibody according to claim 2 , wherein the heavy chain is SEQ ID NO: 42, SEQ ID NO: 43 or SEQ ID NO: 44.
4. The modified anti-PD-L1 antibody according to claim 1 , wherein the light chain variable region is SEQ ID NO: 9.
5. The modified anti-PD-L1 antibody according to claim 1 , wherein the light chain further comprises a kappa light chain constant region.
6. The modified anti-PD-L1 antibody according to claim 5 , wherein the kappa light chain constant region is SEQ ID NO: 16.
7. The modified anti-PD-L1 antibody according to claim 1 , wherein the light chain is SEQ ID NO: 21.
8. A pharmaceutical kit comprising a modified anti-PD-L1 antibody as defined in claim 1 .
9. A pharmaceutical composition comprising a modified anti-PD-L1 antibody as defined in claim 1 .
10. A pharmaceutical kit comprising a pharmaceutical composition as defined in claim 9 .
11. A modified anti-Programmed Death Ligand 1 (PD-L1) antibody comprising a heavy chain comprising a heavy chain variable region of SEQ ID NO: 2 and a heavy chain constant region of SEQ ID NO: 55, SEQ ID NO: 56, or SEQ ID NO: 57; and a light chain comprising a light chain variable region of SEQ ID NO: 9 and a light chain constant region of SEQ ID NO: 16.
12. The modified anti-PD-L1 antibody according to claim 11 , wherein the heavy chain is SEQ ID NO: 42, SEQ ID NO: 43 or SEQ ID NO: 44.
13. A pharmaceutical kit comprising a modified anti-PD-L1 antibody as defined in claim 11 .
14. A pharmaceutical composition comprising a modified anti-PD-L1 antibody as defined in claim 11 .
15. A pharmaceutical kit comprising a pharmaceutical composition as defined in claim 14 .
16. A modified anti-Programmed Death Ligand 1 (PD-L1) antibody comprising a heavy chain of SEQ ID NO: 42, SEQ ID NO: 43, or SEQ ID NO: 44; and a light chain of SEQ ID NO: 21.
17. A pharmaceutical kit comprising a modified anti-PD-L1 antibody as defined in claim 16 .
18. A pharmaceutical composition comprising a modified anti-PD-L1 antibody as defined in claim 16 .
19. A pharmaceutical kit comprising a pharmaceutical composition as defined in claim 18 .