Antibodies capable of binding to cd27, variants thereof and uses thereof

Abstract

The present invention relates to antibodies capable of binding to human CD27 and to variants thereof comprising a modified Fc region comprising one or more mutations that enhances the Fc-Fc interaction of the antibody. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.

1 - 65 . (canceled) 
     
     
         66 . An anti-CD27 antibody, or antigen binding fragment thereof, that specifically binds to human CD27, wherein the antibody or antigen binding fragment further comprises a human heavy chain constant region IgG, wherein the amino acid residue at the position corresponding to position E345 or E430 in the human IgG1 heavy chain according to Eu numbering is selected from the group comprising: A, C, D, F, G, H, I, K, L, M, N, Q, R, S, T, V, W and Y.. 
     
     
         67 . The antibody of  claim 66 , wherein the amino acid residue at the position corresponding to position E345 in the human IgG1 heavy chain according to Eu numbering is R. 
     
     
         68 . The antibody of  claim 66 , wherein the amino acid residue at the position corresponding to position E430 in the human IgG1 heavy chain according to Eu numbering is G. 
     
     
         69 . The antibody of  claim 66 , wherein the amino acid residue at the position corresponding to position P329 in the human IgG1 heavy chain according to Eu numbering is R. 
     
     
         70 . The antibody of  claim 66 , wherein the amino acid residue at the positions corresponding to position E345 and P329 in a human IgG1 heavy chain according to Eu numbering are both R. 
     
     
         71 . A pharmaceutical composition comprising the anti-CD27 antibody of  claim 66  and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         72 . An anti-CD27 antibody, or antigen binding fragment thereof, that specifically binds to human CD27, wherein the antibody or antigen binding fragment comprises a heavy chain variable (VH) region CDR1, CDR2, and CDR3 comprising the sequences as set forth in SEQ ID NOs: 5, 6, and 7, respectively, and a light chain variable (VL) region CDR1, CDR2, and CDR3 comprising the sequences as set forth in SEQ ID NO: 9, 10 and 11, respectively. 
     
     
         73 . The antibody of  claim 72 , wherein the antibody comprises the heavy chain constant region comprising a sequence selected from the group comprising: SEQ ID Nos 12, 13, 14, 15, 18, 19, 20, 21, 22, 23, 27, 28, 29, 30, 31, 32, 33, 34 and 36. 
     
     
         74 . The antibody of  claim 72 , wherein the antibody comprises the heavy chain constant region comprising the sequence as set forth in SEQ ID No 15. 
     
     
         75 . A pharmaceutical composition comprising the anti-CD27 antibody of  claim 72  and a pharmaceutically acceptable carrier. 
     
     
         76 . An anti-CD27antibody, or antigen binding fragment thereof, that specifically binds to human CD27, the antibody or antigen binding fragment comprising VH and VL regions comprising the sequences as set forth in SEQ ID NO: 4 and SEQ ID NO: 8, respectively. 
     
     
         77 . The antibody of  claim 75 , wherein the anti-CD27 antibody further comprises a human heavy chain constant region IgG 1. 
     
     
         78 . The antibody of  claim 75 , wherein the antibody comprises the heavy chain constant region comprising a sequence selected from the group comprising: SEQ ID Nos 12, 13, 14, 15, 18, 19, 20, 21, 22, 23, 27, 28, 29, 30, 31, 32, 33, 34 and 36. 
     
     
         79 . The antibody of  claim 75 , wherein the antibody further comprises:
 a. The heavy chain constant region comprising the amino acid sequence set forth in SEQ ID No: 15; and   b. The light chain constant region comprising the amino acid sequence set forth in SEQ ID No: 17.   
     
     
         80 . A pharmaceutical composition comprising the anti-CD27 antibody of  claim 75  and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         81 . An anti-CD27 antibody that specifically binds to human CD27, wherein the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 35 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 25. 
     
     
         82 . A pharmaceutical composition comprising the anti-CD27 antibody of  claim 81  and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         83 . A method of treating cancer, an inflammatory and/or autoimmune disease or disorder, the method comprising administering to the subject the pharmaceutical composition of  claim 71 . 
     
     
         84 . A method of treating cancer, an inflammatory and/or autoimmune disease or disorder, the method comprising administering to the subject the pharmaceutical composition of  claim 75 . 
     
     
         85 . A method of treating cancer, an inflammatory and/or autoimmune disease or disorder, the method comprising administering to the subject the pharmaceutical composition of  claim 80 . 
     
     
         86 . A method of treating cancer, an inflammatory and/or autoimmune disease or disorder, the method comprising administering to the subject the pharmaceutical composition of  claim 82 . 
     
     
         87 . A polynucleotide sequence, or set of polynucleotides, encoding the anti-CD27 antibody of  claim 66 , or a host cell comprising said polynucleotide sequence of set of polynucleotides. 
     
     
         88 . A polynucleotide sequence, or set of polynucleotides, encoding the anti-CD27 antibody of  claim 72 , or a host cell comprising said polynucleotide sequence of set of polynucleotides. 
     
     
         89 . A polynucleotide sequence, or set of polynucleotides, encoding the anti-CD27 antibody of  claim 76 , or a host cell comprising said polynucleotide sequence of set of polynucleotides. 
     
     
         90 . A polynucleotide sequence, or set of polynucleotides, encoding the anti-CD27 antibody of  claim 81 , or a host cell comprising said polynucleotide sequence of set of polynucleotides. 
     
     
         91 . A method of making an anti-CD27 antibody comprising culturing the host cell of  claim 87  under conditions to produce the antibody and recovering the antibody. 
     
     
         92 . A method of making an anti-CD27 antibody comprising culturing the host cell of  claim 88  under conditions to produce the antibody and recovering the antibody. 
     
     
         93 . A method of making an anti-CD27 antibody comprising culturing the host cell of  claim 89  under conditions to produce the antibody and recovering the antibody. 
     
     
         94 . A method of making an anti-CD27 antibody comprising culturing the host cell of  claim 89  under conditions to produce the antibody and recovering the antibody. 
     
     
         95 . An anti-idiotypic antibody, which binds to the antibody or antigen binding fragment of  claim 66 .