Il-21 binding proteins and uses thereof

Abstract

The present disclosure provides proteins comprising antigen binding sites of antibodies that bind to interleukin-21 (IL-21) and uses thereof, e.g., in therapy.

1 . A pharmaceutical composition comprising an IL-21-binding protein, and a non-toxic pharmaceutically acceptable carrier wherein the IL-21-binding protein comprises an antigen binding domain that binds to IL-21 and which comprises:
 (i) a heavy chain variable region (V H ) comprising three complementarity determining regions (CDRs), wherein the three CDRs are the same as the three CDRs of the amino acid sequence set forth in SEQ ID NO:2; and   (ii) a light chain variable region (V L ) comprising three complementarity determining regions (CDRs), wherein the three CDRs are the same as the three CDRs of the amino acid sequence set forth in SEQ ID NO:3.   
     
     
         2 . A pharmaceutical composition according to  claim 1  wherein the IL-21 binding protein is chimeric, humanized, human, CDR-grafted, primatized or de-immunised. 
     
     
         3 . A pharmaceutical composition according to  claim 1  wherein the IL-21 binding protein comprises:
 (i) a V H  comprising a CDR1 comprising the sequence set forth in SEQ ID NO:5, a CDR2 comprising the sequence set forth in SEQ ID NO:6 and a CDR3 comprising the sequence set forth in SEQ ID NO:7; and 
 (ii) a V L  comprising a CDR1 comprising the sequence set forth in SEQ ID NO:8, a CDR2 comprising the sequence set forth in SEQ ID NO:9 and a CDR3 comprising the sequence set forth in SEQ ID NO:10. 
 
     
     
         4 . A pharmaceutical composition according to  claim 1  wherein the IL-21 binding protein comprises:
 (i) a V H  comprising a CDR1 comprising the sequence set forth in SEQ ID NO:11, a CDR2 comprising the sequence set forth in SEQ ID NO:12 and a CDR3 comprising the sequence set forth in SEQ ID NO:13; and 
 (ii) a V L  comprising a CDR1 comprising the sequence set forth in SEQ ID NO:14, a CDR2 comprising the sequence set forth in SEQ ID NO:15 and a CDR3 comprising the sequence set forth in SEQ ID NO:16. 
 
     
     
         5 . A pharmaceutical composition according to  claim 1 , wherein the antigen binding domain of the IL-21-binding protein comprises a V H  comprising a sequence at least 95% identical to the sequence set forth in SEQ ID NO:2. 
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the antigen binding domain of the IL-21-binding protein comprises a V L  comprising a sequence at least 95% identical to the sequence set forth in SEQ ID NO:3. 
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the antigen binding domain of the IL-21-binding protein comprises a V H  comprising the sequence set forth in SEQ ID NO:2. 
     
     
         8 . A pharmaceutical composition according to  claim 1 , wherein the antigen binding domain of the IL-21-binding protein comprises a V L  comprising the sequence set forth in SEQ ID NO:3. 
     
     
         9 . A pharmaceutical composition according to  claim 1 , wherein the antigen binding domain of the IL-21-binding protein comprises a V H  comprising the sequence set forth in SEQ ID NO:2 and a V L  comprising the sequence set forth in SEQ ID NO:3. 
     
     
         10 . A pharmaceutical composition according to  claim 1  wherein the antigen binding domain of the IL-21 binding protein binds to a peptide consisting of the amino acid sequence of SEQ ID NO:4. 
     
     
         11 . A pharmaceutical composition according to  claim 1  wherein the antigen binding domain of the IL-21 binding protein binds to a peptide consisting of the amino acid sequence of SEQ ID NO:22. 
     
     
         12 . A pharmaceutical composition according to  claim 1 , wherein the antigen binding domain of the IL-21-binding protein comprises at least a heavy chain variable region (V H  ) and a light chain variable region (V L ), wherein the V H  and V L  bind to form a Fv comprising an antigen binding domain, wherein the V H  and the V L  are in a single polypeptide chain or the V L  and V H  are in separate polypeptide chains. 
     
     
         13 . A pharmaceutical composition according to  claim 12 , wherein if the V H  and V L  are in a single polypeptide chain, the protein is:
 (i) a single chain Fv fragment (scFv);   (ii) a dimeric scFv (di-scFv);   (iii) one of (i) or (ii) linked to a constant region of an antibody, Fc or a heavy chain constant domain (CH)2 and/or CH3.   
     
     
         14 . A pharmaceutical composition according to  claim 12 , wherein if the V H  and V L  are in separate polypeptide chains the protein is:
 (i) a diabody;   (ii) a triabody;   (iii) a tetrabody;   (iv) a Fab;   (v) a F(ab′)2;   (vi) a Fv;   (vii) one of (i) to (vi) linked to a constant region of an antibody, Fc or a heavy chain constant domain (C H ) 2 and/or C H 3; or   (viii) an antibody.   
     
     
         15 . A pharmaceutical composition according to  claim 1 , wherein the IL-21-binding protein is not conjugated to another compound. 
     
     
         16 . A pharmaceutical composition according to  claim 1 , wherein the composition is formulated for parenteral administration, including intravenous administration, or administration into a body cavity or lumen of an organ or joint. 
     
     
         17 . A pharmaceutical composition according to  claim 1 , wherein the composition further comprises one or more immunotherapeutic compounds. 
     
     
         18 . A pharmaceutical composition according to  claim 17 , wherein the immunotherapeutic compound is selected from a checkpoint inhibitor, tyrosine kinase inhibitor, tumor necrosis factor receptor inhibitor, cytokine or interleukin;
 interferon; granulocyte macrophage colony stimulating factor; vaccine (cancer vaccine or infectious disease); antiviral drug or an oncolytic virus.   
     
     
         19 . A pharmaceutical composition according to  claim 18 , wherein the checkpoint inhibitor is an inhibitor of Programmed cell death protein 1 (PD-1), Programmed cell death 1 ligand 1 (PDL-1) or Programmed death 1 ligand 2 (PDL-2), Cluster of Differentiation 80 (CD80), Cluster of Differentiation 86 (CD86), B7-related protein 1 (B7RP1), Cluster of Differentiation 276 (CD276), Herpes virus entry mediator (HVEM), Cluster of Differentiation 137-Ligand (CD137L), Tumor Necrosis Factor Superfamily Member 4 Ligand (OX40L), Cluster of Differentiation 70 (CD70), Cluster of Differentiation 40 (CD40), Galectin 9 (GAL9), Cluster of Differentiation 28 (CD28), Cytotoxic T-lymphocyte activator-4 (CTLA4), Inducible T-cell costimulator (ICOS), B and T lymphocyte attenuator (BTLA), Killer cell immunoglobulin-like receptor (KIR), Lymphocyte-activation gene 3 (LAG3), Death receptor 5 (DR5), Cluster of Differentiation 137 (CD137), Tumor Necrosis Factor Superfamily Member 42 (OX40), Cluster of Differentiation 27 (CD27), Cluster of Differentiation 40 Ligand (CD4OL), adenosine receptor A2a (A2aR) or T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3).