Pd1 binding agents

Abstract

Provided herein are antibody molecules that bind specifically to Programmed cell death 1 (PD1) and related nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.

What is claimed is: 
     
         1 . A nucleic acid molecule encoding the heavy chain variable (VH) region amino acid sequence and the light chain variable (VL) region amino acid sequence of an anti-PD1 antibody or an antigen-binding portion thereof, wherein
 (a) the VH region amino acid sequence comprises HCDR1 of GFTFSSYGMS (SEQ ID NO:33), HCDR2 of VANIWQDGSTKYVDSVKG (SEQ ID NO:34), and HCDR3 of AYGNYWYIDR (SEQ ID NO:35); and the VL region amino acid sequence comprises LCDR1 of KSSQSVTNDVA (SEQ ID NO:36), LCDR2 of YAYHRFT (SEQ ID NO:37), and LCDR3 of HQAYSTPYT (SEQ ID NO:46); or   (b) the VH region amino acid sequence comprises HCDR1 of GFSLSSYGMS (SEQ ID NO:39), HCDR2 of VAVIWQDGSTNYVDSVKG (SEQ ID NO:40), and HCDR3 of AYGNYWYIDR (SEQ ID NO:35); and the VL region amino acid sequence comprises LCDR1 of KSSQSVTNDVA (SEQ ID NO:36), LCDR2 of YAYHRFT (SEQ ID NO:37), and LCDR3 of HQAYSTPYT (SEQ ID NO:46).   
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein
 (a) the VH region amino acid sequence comprises SEQ ID NO:1 and the VL region amino acid sequence comprises SEQ ID NO:2; or   (b) the VH region amino acid sequence comprises SEQ ID NO:3 and the VL region amino acid sequence comprises SEQ ID NO:4.   
     
     
         3 . The nucleic acid molecule of  claim 1 , wherein the antibody or antigen-binding portion is humanized or chimeric. 
     
     
         4 . The nucleic acid molecule of  claim 1 , wherein the VH region, the VL region, or both the VH and the VL region comprise one or more human framework region amino acid sequences. 
     
     
         5 . The nucleic acid molecule of  claim 1 , wherein the VH region, the VL region, or both the VH and the VL region comprise a human variable region framework scaffold amino acid sequence into which the CDRs have been inserted. 
     
     
         6 . The nucleic acid molecule of  claim 1 , wherein the VH region comprises an IGHV3-7 human germline scaffold amino acid sequence into which the HCDR1, HCDR2 and HCDR3 amino acid sequences have been inserted. 
     
     
         7 . The nucleic acid molecule of  claim 1 , wherein the VL region comprises an IGKV1-39 human germline scaffold amino acid sequence into which the LCDR1, LCDR2 and LCDR3 amino acid sequences have been inserted. 
     
     
         8 . The nucleic acid molecule of  claim 1 , wherein the nucleic acid molecule further encodes an immunoglobulin constant region. 
     
     
         9 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region is IgG, IgE, IgM, IgD, IgA or IgY. 
     
     
         10 . The nucleic acid molecule of  claim 9 , wherein the immunoglobulin constant region is IgG1, IgG2, IgG3, IgG4, IgA1 or IgA2. 
     
     
         11 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region is immunologically inert. 
     
     
         12 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region is a wild-type human IgG4 constant region, a human IgG4 constant region comprising the amino acid substitution S228P, a wild-type human IgG1 constant region, a human IgG1 constant region comprising the amino acid substitutions L234A, L235A and G237A or a wild-type human IgG2 constant region, wherein numbering is according to the EU index as in Kabat. 
     
     
         13 . The nucleic acid molecule of  claim 8 , wherein the immunoglobulin constant region comprises any one of SEQ ID NOS:9-15. 
     
     
         14 . The nucleic acid molecule of  claim 1 , wherein the antibody or antigen-binding portion is an Fab, an Fab′, an F(ab′) 2 , an Fv, an scFv, a maxibody, a minibody, an intrabody, a diabody, a triabody, a tetrabody, or a bis-scFv. 
     
     
         15 . An expression vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         16 . A recombinant host cell comprising the nucleic acid molecule of  claim 1 . 
     
     
         17 . A recombinant host cell comprising the expression vector of  claim 15 .