MULTISPECIFIC ANTIBODIES FOR IMMUNO-ONCOLOGY

1 . A multispecific antibody which binds ICOS and another target antigen.

2 . (canceled)

3 . The multispecific antibody according to claim 1 , which comprises a VH domain comprising a CDRH1, a CDRH2 and a CDRH3 which VH domain binds human (hICOS).

4 . The multispecific antibody according to claim 1 , which comprises a VL domain comprising a CDRL1, a CDRL2 and a CDRL3, which VL domain binds human (hICOS).

5 - 6 . (canceled)

7 . The multispecific antibody of claim 1 , which has agonistic activity against ICOS.

8 . (canceled)

9 . The multispecific antibody of claim 1 , which is a bispecific antibody.

10 . The multispecific antibody according to claim 9 , which is a dual binding antibody.

11 . The multispecific antibody according to claim 10 , which is a FIT-Ig.

12 . The multispecific antibody of claim 1 , wherein the another target antigen is selected from immune checkpoint inhibitors, immune modulators and immune activators.

13 - 14 . (canceled)

15 . The multispecific antibody according to claim 1 , wherein the another target antigen is PD-L1.

16 . (canceled)

17 . The multispecific antibody of claim 15 , which comprises a VH domain comprising a CDRH1, a CDRH2 and a CDRH3 which VH domain has specificity for human PD-L1.

18 . The multispecific antibody according to claim 15 , which comprises a VL domain comprising a CDRL1, a CDRL2 and a CDRL3, which VL domain has specificity for human PD-L1.

19 - 20 . (canceled)

21 . The multispecific antibody according to claim 15 , which binds mouse PD-L1 and/or cynomolgus PD-L1.

22 . A composition comprising the multispecific antibody of claim 1 and a pharmaceutically acceptable excipient, diluent or carrier and, optionally, further comprising a further therapeutic agent independently selected from the group consisting of:

a) other immune checkpoint inhibitors;

b) immune stimulators;

c) chemokine receptor antagonists;

d) targeted kinase inhibitors;

e) angiogenesis inhibitors;

f) immune stimulating peptides or chemokines;

g) cytokines;

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

i) other bi-specific molecules;

j) oncolytic viruses;

k) vaccination with tumour associated antigens;

l) cell-based therapies; and

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

23 - 24 . (canceled)

25 . A method of treating or preventing a disease or condition selected from neurological disease, neoplastic or non-neoplastic disease, chronic viral infections, and malignant tumours, such as melanoma, Merkel cell carcinoma, non-small cell lung cancer (squamous and non-squamous), renal cell cancer, bladder cancer, head and neck squamous cell carcinoma, mesothelioma, virally induced cancers, soft tissue sarcomas, haematological malignancies such as Hodgkin's and non-Hodgkin's disease and diffuse large B-cell lymphoma in a human, comprising administering to said human a therapeutically effective amount of the multispecific antibody of claim 1 , wherein the disease or condition is thereby treated or prevented.

26 . (canceled)

27 . The method according to claim 25 , wherein the cancer is selected from melanoma, Merkel cell carcinoma, non-small cell lung cancer (squamous and non-squamous), renal cell cancer, bladder cancer, head and neck squamous cell carcinoma and mesothelioma or is selected from virally induced cancers and soft tissue sarcomas.

28 . The method according to claim 25 , further comprising administering to the human a further therapy, for example a further therapeutic agent, optionally wherein the further therapeutic agent is independently selected from the group consisting of:

a) other immune checkpoint inhibitors;

b) immune stimulators;

c) chemokine receptor antagonists;

d) targeted kinase inhibitors;

e) angiogenesis inhibitors;

f) immune stimulating peptides or chemokines;

g) cytokines;

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

i) other bi-specific molecules;

j) oncolytic viruses;

k) vaccination with tumour associated antigens;

l) cell-based therapies (such as chimeric Antigen Receptor-T-cells (CAR-T) for example expressing anti-CD19, anti-EpCam or anti-mesothelin); and

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

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

29 . A nucleic acid that encodes a heavy chain and/or a light chain of the multispecific antibody of claim 1 .

30 . A vector comprising the nucleic acid as defined in claim 29 ;.

31 . A host cell comprising the vector as defined in claim 30 .

32 . A multispecific which binds ICOS; wherein the multispecific antibody comprises a binding arm that binds PD-L1, wherein the binding arm that binds PD-L1 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein

the anti-PD-L1 VH and VL domains are 1D05 VH and VL domains comprising a heavy chain amino acid sequence of Seq ID No:299 and a light chain amino acid sequence of Seq ID No:300 respectively, and wherein

the antibody is an immunocytokine comprising human wild type or variant IL-2.