MULTISPECIFIC ANTIBODIES FOR IMMUNO-ONCOLOGY

1 - 32 . (canceled)

33 . A multispecific antibody comprising a first polypeptide, a second polypeptide, and a third polypeptide, wherein the first polypeptide, the second polypeptide, and the third polypeptide form a Fab-scFv-Fc multispecific antibody,

wherein the first polypeptide comprises, from N- to C-terminus, a light chain variable region A, a light chain constant region (CL),

wherein the second polypeptide comprises, from N- to C-terminus, a heavy chain variable region A, a CH1 heavy chain constant region, and heavy chain constant regions CH2 and CH3,

wherein the third polypeptide comprises, from N- to C-terminus, a single chain fragment variable region B, and heavy chain constant regions CH2 and CH3,

wherein the light chain variable region A and the heavy chain variable region A bind an immune activator, and

wherein the single chain fragment variable region B binds an immune check point inhibitor.

34 . A composition comprising the multispecific antibody according to claim 33 and a pharmaceutically acceptable excipient, diluent, or carrier.

35 . The composition according to claim 34 , further comprising a therapeutic agent selected from the group consisting of:

a) immune checkpoint inhibitors;

b) immune stimulators;

c) chemokine receptor antagonists;

d) targeted kinase inhibitors;

e) angiogenesis inhibitors;

f) cytokines;

g) bispecific T-cell engagers (BiTEs) having at least one specificity against CD3;

h) bi-specific molecules;

i) oncolytic viruses;

j) vaccination with tumour associated antigens;

k) cell-based therapies; and

1) adoptive transfer of tumour specific T-cells or LAK cells.

36 . The method of treating a solid tumor in a human, wherein the immune activator is an agonistic anti-ICOS antibody and the immune check point inhibitor is an anti-PD-1 antibody.

37 . The method of treating a solid tumor in a human, comprising administering to the human a therapeutically effective amount of a multispecific antibody according to claim 33 .

38 . The method according to claim 37 , further comprising administering to the human a further therapy, optionally a further therapeutic agent, optionally wherein the further therapeutic agent is selected from the group consisting of:

a) immune checkpoint inhibitors

b) immune stimulators;

c) chemokine receptor antagonists;

d) targeted kinase inhibitors;

e) angiogenesis inhibitors;

f) bispecific T-cell engagers (BiTEs) having at least one specificity against CD3;

g) other bi-specific molecules;

h) oncolytic viruses

i) vaccination with tumour associated antigens;

j) cell-based therapies; and

k) adoptive transfer of tumour specific T-cells or LAK cells,

or optionally wherein the further therapy is chemotherapy, radiotherapy, and/or surgical removal of tumour.

39 . The method of claim 37 , wherein the immune stimulator is an immune stimulating peptide, a chemokine, or a cytokine.

40 . A nucleic acid that encodes the first polypeptide, the second polypeptide, or the third polypeptide of the multispecific antibody according to claim 33 .

41 . A vector comprising the nucleic acid according to claim 40 ; optionally wherein the vector is a CHO or HEK293 vector.

42 . An isolated host cell comprising the vector according to claim 41 .

43 . A multispecific antibody comprising a first polypeptide, a second polypeptide, and a third polypeptide, wherein the first polypeptide, the second polypeptide, and the third polypeptide form a Fab-scFv-Fc multispecific antibody,

wherein the first polypeptide comprises, from N- to C-terminus, a light chain variable region A, a light chain constant region (CL),

wherein the second polypeptide comprises, from N- to C-terminus, a heavy chain variable region A, a CH1 heavy chain constant region, and heavy chain constant regions CH2 and CH3,

wherein the third polypeptide comprises, from N- to C-terminus, a single chain fragment variable region B, and heavy chain constant regions CH2 and CH3,

wherein the light chain variable region A and the heavy chain variable region A binds immune check point inhibitor, and

wherein the single chain fragment variable region B binds immune activator.

44 . A composition comprising the multispecific antibody according to claim 43 and a pharmaceutically acceptable excipient, diluent, or carrier.

45 . The composition according to claim 43 , further comprising a therapeutic agent selected from the group consisting of:

a) immune checkpoint inhibitors;

b) immune stimulators;

c) chemokine receptor antagonists;

d) targeted kinase inhibitors;

e) angiogenesis inhibitors;

f) cytokines;

g) bispecific T-cell engagers (BiTEs) having at least one specificity against CD3;

h) bi-specific molecules;

i) oncolytic viruses;

j) vaccination with tumour associated antigens;

k) cell-based therapies; and

1) adoptive transfer of tumour specific T-cells or LAK cells.

46 . The method of treating a solid tumor in a human, comprising administering to the human a therapeutically effective amount of a multispecific antibody according to claim 43 .

47 . The method according to claim 45 , further comprising administering to the human a further therapy, optionally a further therapeutic agent, optionally wherein the further therapeutic agent is selected from the group consisting of:

a) immune checkpoint inhibitors

b) immune stimulators;

c) chemokine receptor antagonists;

d) targeted kinase inhibitors;

e) angiogenesis inhibitors;

f) bispecific T-cell engagers (BiTEs) having at least one specificity against CD3;

g) other bi-specific molecules;

h) oncolytic viruses

i) vaccination with tumour associated antigens;

j) cell-based therapies; and

k) adoptive transfer of tumour specific T-cells or LAK cells,

or optionally wherein the further therapy is chemotherapy, radiotherapy, and/or surgical removal of tumour.

48 . The method of claim 47 , wherein the immune stimulator is an immune stimulating peptide, a chemokine, or a cytokine.

49 . The method of treating a solid tumor in a human, wherein the immune activator is an agonistic anti-ICOS antibody and the immune check point inhibitor is an anti-PD-1 antibody.

50 . A nucleic acid that encodes the first polypeptide, the second polypeptide, or the third polypeptide of the multispecific antibody according to claim 43 .

51 . A vector comprising the nucleic acid according to claim 50 ; optionally wherein the vector is a CHO or HEK293 vector.

52 . An isolated host cell comprising the vector according to claim 51 .