Antibodies directed to PDGFD and uses thereof

Abstract

The present invention is related to antibodies directed to the antigen PDGFD and uses of such antibodies. In particular, in accordance with the present invention, there are provided fully human monoclonal antibodies directed to the antigen PDGFD. Nucelotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.

1 . An isolated human monoclonal antibody or binding fragment thereof that binds to PDGFD.  
     
     
         2 . The antibody of  claim 1 , comprising a heavy chain amino acid sequence derived from a human germline sequence selected from the group consisting of SEQ ID NOS:1, 2, 3, 4, 5 and 6.  
     
     
         3 . The human monoclonal antibody of  claim 2 , further comprising a light chain amino sequence derived from a human germline sequence selected from the group consisting of SEQ ID NOS:7, 8, 9, 10 and 11.  
     
     
         4 . The human monoclonal antibody of  claim 1 , comprising a heavy chain CDR1 amino acid sequence comprising G (Y/F) X 1  (F/V) (T/R/S) (S/T) (Y/N) X 2  (I/M) X 3 .  
     
     
         5 . The human monoclonal antibody of  claim 1 , comprising a heavy chain CDR2 amino acid sequence comprising (M/I) X 1  X 2  X 3  X 4  (G/S/N) (N/D) X 5  X 6  Y (A/S) (Q/D/P) (K/S) (F/UV) (Q/K) G.  
     
     
         6 . The human monoclonal antibody of  claim 1 , comprising a heavy chain CDR3 amino acid sequence selected from the group consisting of: amino acid residues 99-115 of SEQ ID NOS:38, 42, 48; residues 99-116 of SEQ ID NOS:13, 17, 19, 21, 23, 25, 27, 35, 37, 40, 46; residues 99-117 of SEQ ID NOS: 31, 33, 44; residues 99-119 of SEQ ID NO:29; and residues 99-110 of SEQ ID NO:15.  
     
     
         7 . The human monoclonal antibody of  claim 1 , comprising a light chain CDR1 amino acid sequence comprising R (A/S)S Q (G/S) (I/L/V) (S/L/R) (S/H/Q/N) X 0-5  (W/Y/D) L (A/D/G).  
     
     
         8 . The human monoclonal antibody of  claim 1 , comprising a light chain CDR2 amino acid sequence comprising (A/L/G) (A/G/T) S (I/S/N/T) (L/R) (Q/A/P) (S/L/T/R).  
     
     
         9 . The human monoclonal antibody of  claim 1 , comprising a light chain CDR3 amino acid sequence comprising (Q/M/L) (Q/K) X 1  X 2  (S/Q/G) X 3  (P/I/L) X 4  (T/C/S) (−/S).  
     
     
         10 - 21 . (canceled)  
     
     
         22 . The antibody of  claim 4 , wherein X 1  is T, S, N or R.  
     
     
         23 . The antibody of  claim 4 , wherein X 2  is D, G, N, Y or W.  
     
     
         24 . The antibody of  claim 4 , wherein X 3  is N, S, H or G.  
     
     
         25 . The antibody of  claim 4 , wherein said CDR1 comprises an amino acid sequence selected from the group consisting of residues 26-35 of SEQ ID NOS:13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 38, 40, 42, 44, 46 and 48.  
     
     
         26 . The antibody of  claim 5 , wherein X 1  is N, S, W or Y.  
     
     
         27 . The antibody of  claim 5 , wherein X 2  is P, A, S or Y.  
     
     
         28 . The antibody of  claim 5 , wherein X 3  is N, Y, S, D or G.  
     
     
         29 . The antibody of  claim 5 , wherein X 4  is S, N, G or D.  
     
     
         30 . The antibody of  claim 5 , wherein X 5  is T, I, K or A  
     
     
         31 . The antibody of  claim 5 , wherein X 6  is G, D, N, Y, R or K.  
     
     
         32 . The antibody of  claim 5 , wherein said CDR2 comprises an amino acid sequence selected from the group consisting of residues 51-66 of SEQ ID NOS: 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 38, 40, 42, 44, 46 and 48.  
     
     
         33 . The antibody of  claim 7 , wherein X is zero.  
     
     
         34 . The antibody of  claim 7 , wherein X is 1 and is amino acid S.  
     
     
         35 . The antibody of  claim 7 , wherein X is 5 and is SNGYNY.  
     
     
         36 . The antibody of  claim 7 , wherein said CDR1 comprises an amino acid sequence selected from the group consisting of: residues 24-34 of SEQ ID NOS:22, 32, 39, 43; residues 24-35 of SEQ ID NO:49; residues 24-39 of SEQ ID NOS: 16, 30 and 45.  
     
     
         37 . The antibody of  claim 8 , wherein said CDR2 comprises an amino acid sequence selected from the group consisting of: residues 50-56 of SEQ ID NO:22, 24, 33, 39, 41, 43; residues 51-57 of SEQ ID NOS:47, 49; and residues 55-61 of SEQ ID NO:45.  
     
     
         38 . The antibody of  claim 9 , wherein X 1  is S, T, A, Y, C or H.  
     
     
         39 . The antibody of  claim 9 , wherein X 2  is N, L, G or S.  
     
     
         40 . The antibody of  claim 9 , wherein X 3  is F, T, S, A, D or Y.  
     
     
         41 . The antibody of  claim 9 , wherein X 4  is R, T, M, F, L, W, C or P.  
     
     
         42 . The antibody of  claim 9  wherein said CDR3 comprises an amino acid sequence selected from the group consisting of: residues 89-97 of SEQ ID NOS:18, 20, 22, 24, 32, 34, 39, 41, 43; residues 90-98 of SEQ ID NOS:47, 49; residues 93-100 of SEQ ID NOS:16, 45; and residues 94-103 of SEQ ID NO:30.  
     
     
         43 . The antibody of  claim 1  wherein said antibody binds to PDGFD with a Kd between 10-6 and 10-11M.  
     
     
         44 . A composition comprising the antibody of  claim 1  in association with a pharmaceutically acceptable carrier.