Binding Members to PD-L1

Abstract

The present invention relates to anti-PD-L1 binding members and in particular to monovalent, high potency PD-L1-binding antibody fragments being highly stable and soluble. Such binding members may be used in the treatment of cancer and inflammatory diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.

1 . (canceled) 
     
     
         2 . A binding member having a binding specificity to PD-L1, comprising
 (i) the variable heavy chain CDR-H1, CDR-H2 and CDR-H3 sequences as set forth in SEQ ID NOs: 6, 7 and 8, or sequences that are at least 90% identical to SEQ ID NOs: 6, 7, and 8 taken as a whole; and   (ii) the variable light chain CDR-L1, CDR-L2 and CDR-L3 sequences as set forth in SEQ ID NOs: 3, 4 and 5, or sequences that are at least 90% identical to SEQ ID NOs: 3, 4, and 5 taken as a whole.   
     
     
         3 . The binding member of  claim 2 , being humanized. 
     
     
         4 . The binding member of  claim 2 , comprising
 (i) a variable light chain having at least 90% sequence identity to SEQ ID NO: 1; and   (ii) a variable heavy chain having at least 90% sequence identity to SEQ ID NO: 2.   
     
     
         5 . The binding member of  claim 2 , further comprising a linker sequence, wherein the linker sequence is the sequence set forth in SEQ ID NO: 10, or a sequence that is at least 90% identical to SEQ ID NO: 10. 
     
     
         6 . The binding member of  claim 4 , comprising SEQ ID NO: 9 or SEQ ID NO: 11 or sequences that are at least 90% identical to SEQ ID NO: 9 or SEQ ID NO: 11. 
     
     
         7 . The binding member of  claim 2 , being or comprising
 (i) an antibody fragment such as a Fab, a Fab′, a F(ab)′ 2 , a scFv, a Fv fragment, a scFab, a nanobody, a VHH or a minimal recognition unit;   (ii) a full-length antibody molecule; and/or   (iii) a non-antibody scaffold such as an affibody, an affilin molecule, an AdNectin, a lipocalin mutein, a DARPin, a Knottin, a Kunitz-type domain, an Avimer, a Tetranectin or a trans-body.   
     
     
         8 . The binding member of  claim 2 , being monovalent or multivalent, wherein the binding member is optionally multispecific, preferably bispecific, more preferably a diabody, a single-chain diabody, a DART, a BiTE, or a tandem scFv. 
     
     
         9 . The binding member of  claim 2 , comprising a Fc domain. 
     
     
         10 . The binding member of  claim 9 , wherein the binding member comprises a constant region selected from the group consisting of human IgG1, IgG2, IgG3 or IgG4 isotype. 
     
     
         11 . (canceled) 
     
     
         12 . The binding member of  claim 9 , wherein said Fc domain which is modified such that it does not induce cytotoxic immune responses. 
     
     
         13 . The binding member of  claim 2 , being chemically or biologically modified. 
     
     
         14 .- 15 . (canceled) 
     
     
         16 . An isolated nucleic acid molecule comprising a sequence encoding the binding member of  claim 2 . 
     
     
         17 .- 18 . (canceled) 
     
     
         19 . A host cell comprising the nucleic acid molecule of  claim 16 . 
     
     
         20 . A composition comprising the binding member of  claim 2 . 
     
     
         21 . The composition of  claim 20 , being a cosmetic, a diagnostic or a pharmaceutical composition. 
     
     
         22 .- 23 . (canceled) 
     
     
         24 . A method of treating a PD-L1-mediated disease, the method comprising administering to a subject in need thereof the pharmaceutical composition of  claim 21 . 
     
     
         25 . The method of  claim 24 , wherein the PD-L1-mediated disease is a cancer. 
     
     
         26 .- 31 . (canceled) 
     
     
         32 . A method of producing the binding member of  claim 2 , the method comprising:
 (i) cultivating a host cell comprising a nucleic acid molecule encoding the binding member of  claim 2 , thereby allowing the binding member to be expressed;   (ii) recovering the binding member; and   (iii) optionally purifying the binding member.   
     
     
         33 . A method of producing the binding member of  claim 2 , the method comprising:
 (a) contacting a cell-free expression system with a nucleic acid product template, the nucleic acid product template encoding the binding member according to  claim 2 ;   (b) allowing transcription and translation of the nucleic acid product template to occur, thereby allowing a reaction mixture to be formed;   (c) recovering the binding member from the reaction mixture; and   (d) optionally purifying the binding member.   
     
     
         34 . (canceled) 
     
     
         35 . A method of detecting the presence of PD-L1 in a biological sample, the method comprising:
 (a) contacting the biological sample with the binding member of  claim 2  under conditions permissive for specific binding of the binding member to PD-L1, and   (b) detecting whether a complex between the binding member and PD-L1 is formed.   
     
     
         36 .- 42 . (canceled)