IP Library › Patent Application 19382784
Patent Application
App. No. 19/382,784

MODIFIED ANTI-PD-L1 ANTIBODY AND METHODS AND USES FOR TREATING A NEURODEGENERATIVE DISEASE

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Patent No.
US None
App. No.
19/382,784
Abstract

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.

Claims (25)

1 - 20 . (canceled)

21 . A polynucleotide comprising a nucleic acid sequence encoding a heavy chain polypeptide of a modified anti-Programmed Death Ligand 1 (PD-L1) antibody, the heavy chain polypeptide comprising a variable region including a complementarity determining region (CDR) 1 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.

22 . The polynucleotide of claim 21 , further comprising a polynucleotide comprising a nucleic acid sequence encoding a light chain polypeptide 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.

23 . The polynucleotide of claim 21 , wherein the nucleic acid sequence encoding the heavy chain comprises SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 79, SEQ ID NO: 80, or SEQ ID NO: 81.

24 . The polynucleotide of claim 22 , wherein the nucleic acid sequence encoding the light chain is SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 86, or SEQ ID NO: 87.

25 . An expression construct comprising a polynucleotide of claim 21 .

26 . The expression construct of claim 25 further comprising a polynucleotide comprising a nucleic acid sequence encoding a light chain comprising a 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.

27 . The expression construct of claim 25 , wherein the polynucleotide comprises a nucleic acid sequence encoding the heavy chain of SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 79, SEQ ID NO: 80, or SEQ ID NO: 81.

28 . The expression construct of claim 26 , wherein the polynucleotide comprises a nucleic acid sequence encoding the light chain of SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 86, or SEQ ID NO: 87.

29 . A host cell comprising a polynucleotide of claim 2 .

30 . A host cell comprising a polynucleotide of claim 22 .

31 . A host cell comprising an expression vector of claim 25 .

32 . A host cell comprising an expression vector of claim 26 .

33 . A method for producing a modified anti-PD-L1 antibody, the method comprising expressing a polynucleotide of claim 21 in a host cell.

34 . A method for producing a modified anti-PD-L1 antibody, the method comprising expressing a polynucleotide of claim 22 in a host cell.

35 . A method for producing a modified anti-PD-L1 antibody, the method comprising expressing an expression construct of claim 25 in a host cell.

36 . A method for producing a modified anti-PD-L1 antibody, the method comprising expressing an expression construct of claim 26 in a host cell.

37 . The method of claim 33 , wherein the expression construct is transiently introduced into the host cell.

38 . The method of claim 33 , wherein the polynucleotide is stably introduced and maintained in the host cell.

39 . The method of claim 33 , comprising producing the antibody in the host cell and isolating the antibody therefrom.

40 . The method of claim 34 , further comprising producing the antibody in the host cell and isolating the antibody therefrom.

41 . The method of claim 35 further comprising expressing in the host cell a second expression construct comprising a nucleic acid sequence encoding a light chain from a modified anti-PD-L1 antibody 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.

42 . The method of claim 35 , further comprising expressing the antibody in a cell and isolating the antibody therefrom.

43 . The method of claim 35 , wherein the expression construct is transiently introduced into the host cell.

44 . The method of claim 35 , wherein the expression construct is stably introduced and maintained in the host cell.