Antibodies to cd70

Abstract

The present invention relates to antibodies and antigen binding fragments thereof which bind to the human CD70 protein with high affinity and display potent inhibition of tumour cell growth.

1 - 49 . (canceled) 
     
     
         50 . A host cell comprising:
 (a) a first polynucleotide encoding a heavy chain variable domain (VH) comprising
 (i) an HCDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 50 (DAGYSNHVPIFDS); 
 (ii) an HCDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 27 (DINNEGGTTYYADSVKG); and 
 (iii) an HCDR1 region comprising the amino acid sequence set forth in SEQ ID NO: 11 (VYYMN), and 
   (b) a second polynucleotide encoding a light chain variable domain (VL) comprising 
 (i) an LCDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 160 (ALFISNPSVE), 
 (ii) an LCDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 119 (NTNTRHS), and 
 (iii) an LCDR1 region comprising the amino acid sequence set forth in SEQ ID NO: 250 (GLKSGSVTSDNFPT). 
   
     
     
         51 . The host cell of  claim 50 , wherein 
 (a) the first polynucleotide encodes a VH comprising an amino acid sequence which is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 223; and/or   (b) the second polynucleotide encodes a VL comprising an amino acid sequence which is at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 241.   
     
     
         52 . The host cell of  claim 50 , wherein:
 (a) the first polynucleotide encodes a VH comprising the amino acid sequence set forth in SEQ ID NO: 223; and/or   (b) the second polynucleotide encodes a VL comprising the amino acid sequence set forth in SEQ ID NO: 241.   
     
     
         53 . The host cell of  claim 50 , wherein:
 (a) the first polynucleotide encodes a human IgG 1  IgG 2 , IgG 3 , or IgG 4  heavy chain constant region; and/or   (b) the second polynucleotide encodes a human kappa light chain constant region or a human lambda light chain constant region.   
     
     
         54 . The host cell of  claim 50 , wherein:
 (a) the first polynucleotide encodes an antibody heavy chain comprising the VH amino acid sequence set forth in SEQ ID NO: 223 and a human IgG 1  heavy chain constant region; and   (b) the second polynucleotide encodes an antibody light chain comprising the VL amino acid sequence set forth in SEQ ID NO: 241 and a human lambda light chain constant region.   
     
     
         55 . The host cell of  claim 50 , wherein the first polynucleotide and the second polynucleotide are comprised within a single vector. 
     
     
         56 . The host cell of  claim 50 , wherein the first polynucleotide and the second polynucleotide are comprised within separate vectors. 
     
     
         57 . The host cell of  claim 50 , wherein the host cell is a Chinese hamster ovary cell. 
     
     
         58 . The host cell of  claim 54 , wherein the host cell is a Chinese hamster ovary cell. 
     
     
         59 . A method of producing an antibody that specifically binds to human CD70 comprising culturing the host cell of  claim 50  so that the polynucleotides are expressed and the antibody is produced. 
     
     
         60 . The method of  claim 59 , wherein the antibody is non-fucosylated. 
     
     
         61 . A method of producing an antibody that specifically binds to human CD70 comprising culturing the host cell of  claim 52  so that the polynucleotides are expressed and the antibody is produced. 
     
     
         62 . A method of producing an antibody that specifically binds to human CD70 comprising culturing the host cell of  claim 53  so that the polynucleotides are expressed and the antibody is produced. 
     
     
         63 . A method of producing an antibody that specifically binds to human CD70 comprising culturing the host cell of  claim 54  so that the polynucleotides are expressed and the antibody is produced. 
     
     
         64 . The method of  claim 63 , wherein the antibody is non-fucosylated. 
     
     
         65 . A method of producing an antibody that specifically binds to human CD70 comprising culturing the host cell of  claim 57  so that the polynucleotides are expressed and the antibody is produced. 
     
     
         66 . The method of  claim 65 , wherein the antibody is non-fucosylated. 
     
     
         67 . A method of producing an antibody that specifically binds to human CD70 comprising culturing the host cell of  claim 58  so that the polynucleotides are expressed and the antibody is produced. 
     
     
         68 . The method of  claim 67 , wherein the antibody is non-fucosylated. 
     
     
         69 . A vector comprising:
 (a) a first polynucleotide encoding a heavy chain variable domain (VH) comprising 
 (i) an HCDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 50 (DAGYSNHVPIFDS); 
 (ii) an HCDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 27 (DINNEGGTTYYADSVKG); and 
 (iii) an HCDR1 region comprising the amino acid sequence set forth in SEQ ID NO: 11 (VYYMN), and 
   (b) a second polynucleotide encoding a light chain variable domain (VL) comprising 
 (i) an LCDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 160 (ALFISNPSVE), 
 (ii) an LCDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 119 (NTNTRHS), and 
 (iii) an LCDR1 region comprising the amino acid sequence set forth in SEQ ID NO: 250 (GLKSGSVTSDNFPT).