Bispecific antibody for icos and pd-l1

Abstract

Multispecific antibody in mAb2 format, comprising an ICOS-binding Fab region and a PD-L1-binding Fcab region. Use of the multispecific antibody in immuno-oncology, including for treatment of solid tumours. Combination therapy including antibody to another immune checkpoint molecule such as PD-1 and CTLA-4, in addition to anti-ICOS and anti-PD-L1.

1 - 40 . (canceled) 
     
     
         41 . A composition comprising isolated nucleic acid sequences or a set of nucleic acid sequences encoding a multispecific antibody comprising a Fab and an Fc region,
 wherein the Fab comprises an ICOS binding site   and wherein the Fc region comprises a PD-L1 binding site, wherein the PD-L1 binding site is provided by a CH3 domain in which residues 14 to 18 are substituted by SGYW (SEQ ID NO: 617), residues 45.1 to 78 are substituted by EPQYWA (SEQ ID NO: 618), and residues 92 to 101 are substituted by SNWRWQLDD (SEQ ID NO: 619).   
     
     
         42 . A method of treating cancer in a human patient comprising administering a multispecific antibody comprising a Fab and an Fc region,
 wherein the Fab comprises an ICOS binding site   and wherein the Fc region comprises a PD-L1 binding site, wherein the PD-L1 binding site is provided by a CH3 domain in which residues 14 to 18 are substituted by SGYW (SEQ ID NO: 617), residues 45.1 to 78 are substituted by EPQYWA (SEQ ID NO: 618), and residues 92 to 101 are substituted by SNWRWQLDD (SEQ ID NO: 619).   
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . The method of  claim 42 , wherein the cancer is associated with Tregs and/or tests positive for expression of ICOS and FOXP3. 
     
     
         46 . The method of  claim 42 , wherein the cancer is head and neck cancer, non small cell lung cancer or cervical cancer. 
     
     
         47 . The method of  claim 42 , wherein the method further comprises administering a CTLA-4 antagonist or an anti-CTLA-4 antibody to the patient. 
     
     
         48 . The method of  claim 47 , wherein the anti-CTLA-4 antibody is ipilimumab or tremelimumab. 
     
     
         49 . The method of  claim 42 , wherein the method further comprises administering a PD-1 antagonist or an anti-PD-1 antibody to the patient. 
     
     
         50 . The method of  claim 49 , wherein the anti-PD-1 antibody is pembrolizumab, nivolumab or genolimzumab. 
     
     
         51 . The nucleic acid sequences or set of nucleic acid sequences of  claim 41 , wherein the Fab comprises a VH domain having a HCDR1, HCDR2 and HCDR3 sequences wherein HCDR1 is SEQ ID NO: 405, HCDR2 is SEQ ID NO: 406, and HCDR3 is SEQ ID NO: 407. 
     
     
         52 . The nucleic acid sequences or set of nucleic acid sequences of  claim 41 , wherein the Fab comprises a VL domain having LCDR1, LCDR2 and LCDR3 sequences wherein LCDR1 is SEQ ID NO: 412, LCDR2 is SEQ ID NO: 413, and LCDR3 is the SEQ ID NO 414. 
     
     
         53 . The nucleic acid sequences or set of nucleic acid sequences of  claim 41 , wherein the Fab comprises a VH domain amino acid sequence at least 90% identical to SEQ ID NO: 408 and a VL domain amino acid sequence at least 90% identical to SEQ ID NO: 415. 
     
     
         54 . A vector comprising the nucleic acid sequences or set of nucleic acid sequences of  claim 41 . 
     
     
         55 . An isolated recombinant host cell transformed with the nucleic acid sequences or set of nucleic acid sequences of  claim 54 . 
     
     
         56 . A method of making the multispecific antibody comprising culturing the host cell of  claim 55  under conditions to produce the antibody and recovering the antibody. 
     
     
         57 . A nucleic acid sequence or a set of nucleic acid sequences encoding a multispecific antibody comprising a Fab and an Fc region,
 wherein the Fab comprises an ICOS binding site   wherein the Fc region comprises a PD-L1 binding site, wherein the PD-L1 binding site is provided by a CH3 domain in which residues 14 to 18 are substituted by SGYW (SEQ ID NO: 617), residues 45.1 to 78 are substituted by EPQYWA (SEQ ID NO: 618), and residues 92 to 101 are substituted by SNWRWQLDD (SEQ ID NO: 619), and   wherein the multispecific antibody comprises a heavy chain comprising amino acid sequence SEQ ID NO: 621.   
     
     
         58 . The nucleic acid sequence or a set of nucleic acid sequences of  claim 57 , comprising a light chain comprising amino acid sequence SEQ ID NO: 623. 
     
     
         59 . The nucleic acid sequence or a set of nucleic acid sequences of  claim 57 , comprising two heavy-light chain pairs, in which the heavy chain comprises amino acid sequence SEQ ID NO: 621 and the light chain comprises amino acid sequence SEQ ID NO: 623. 
     
     
         60 . A vector comprising the nucleic acid sequence or a set of nucleic acid sequences of  claim 57 . 
     
     
         61 . An isolated recombinant host cell transformed with the nucleic acid sequence or a set of nucleic acid sequences of  claim 57 . 
     
     
         62 . A method of making the multispecific antibody comprising culturing the host cell of  claim 61  under conditions to produce the antibody and recovering the antibody.