Anti-cd27 antibodies

Abstract

The present invention relates to anti-CD27 antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.

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         3 . An antibody or antigen binding fragment thereof that binds to human CD27, wherein the antibody or antigen binding fragment comprises:
 a) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 1, wherein X 1 =M; or an amino acid sequence differing from said sequence by 1, 2, or 3 conservative substitutions;   b) a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 2, wherein X 1 =N, X 2 =T, X 3 =N and X 4 =T, or an amino acid sequence differing from said sequence by 1, 2, or 3 conservative substitutions;   c) a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 3, wherein X 1 =M, or an amino acid sequence differing from said sequence by 1, 2, or 3 conservative substitutions;   d) a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 4, wherein X 1 =M, or an amino acid sequence differing from said sequence by 1, 2, or 3 conservative substitutions;   e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 5, wherein X 1 =D and X 2 =T, or an amino acid sequence differing from said sequence by 1, 2, or 3 conservative substitutions; and   f) a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 6, wherein X 1 =W, X 2 =N and X 3 =S, or an amino acid sequence differing from said sequence by 1, 2, or 3 conservative substitutions.   
     
     
         4 . An antibody or antigen binding fragment thereof that binds to human CD27 comprising a light chain immunoglobulin variable region, a heavy chain immunoglobulin variable region or both a light chain and a heavy chain immunoglobulin variable region selected from the group consisting of:
 a) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:7 or an amino acid sequence differing from SEQ ID NO: 7 by 1, 2, or 3 conservative substitutions and/or a variable light chain comprising the amino acid sequence of SEQ ID NO: 8 or an amino acid sequence differing from SEQ ID NO: 8 by 1, 2, or 3 conservative substitutions;   b) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence differing from SEQ ID NO: 9 by 1, 2, or 3 conservative substitutions and/or a variable light chain comprising the amino acid sequence of SEQ ID NO: 14 or an amino acid sequence differing from SEQ ID NO: 14 by 1, 2, or 3 conservative substitutions;   c) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 32 or an amino acid sequence differing from SEQ ID NO: 32 by 1, 2, or 3 conservative substitutions and/or a variable light chain comprising the amino acid sequence of SEQ ID NO: 33 or an amino acid sequence differing from SEQ ID NO: 33 by 1, 2, or 3 conservative substitutions;   d) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence differing from SEQ ID NO: 34 by 1, 2, or 3 conservative substitutions and/or a variable light chain comprising the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence differing from SEQ ID NO: 35 by 1, 2, or 3 conservative substitutions;   e) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 39 or an amino acid sequence differing from SEQ ID NO: 39 by 1, 2, or 3 conservative substitutions and/or a variable light chain comprising the amino acid sequence of SEQ ID NO: 40 or an amino acid sequence differing from SEQ ID NO: 40 by 1, 2, or 3 conservative substitutions;   f) an antibody or antigen binding fragment thereof comprising a variable heavy chain selected from the group consisting of SEQ ID Nos: 10-13 or an amino acid sequence differing from one of SEQ ID Nos: 10-13 by 1, 2, or 3 conservative substitutions and/or a variable light chain selected from the group consisting of any one of SEQ ID Nos: 15-18 or an amino acid sequence differing from one of SEQ ID Nos: 15-18 by 1, 2, or 3 conservative substitutions;   g) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence differing from SEQ ID NO: 10 by 1, 2, or 3 conservative substitutions and/or a variable light chain comprising the amino acid sequence of SEQ ID NO: 15 or an amino acid sequence differing from SEQ ID NO: 15 by 1, 2, or 3 conservative substitutions;   h) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90% identity to any one of SEQ ID Nos: 10-13 and/or a variable light chain comprising at least 90% identity to any one of SEQ ID Nos: 15-18;   i) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising at least 90% identity to any one of SEQ ID Nos: 10-13 and/or a variable light chain comprising at least 90% identity to any one of SEQ ID Nos: 15-18, wherein any sequence variations occur in the framework regions of the antibody or antigen binding fragment;   j) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions with respect to any one of SEQ ID Nos: 10-13 and/or a variable light chain comprising 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions with respect to any one of SEQ ID Nos: 15-18; and   k) an antibody or antigen binding fragment thereof comprising a variable heavy chain comprising 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions with respect to any one of SEQ ID Nos: 10-13 and/or a variable light chain comprising 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions with respect to any one of SEQ ID Nos: 15-18, wherein the amino acid substitutions occur in the framework regions of the antibody or antigen binding fragment.   
     
     
         5 . The antibody or antigen binding fragment thereof of  claim 4 , comprising a light chain and a heavy chain immunoglobulin variable region selected from the group consisting of:
 a) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 14;   b) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 32 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 33; and   c) a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 34 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 35.   
     
     
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         13 . An antibody or antigen binding fragment thereof that binds the same epitope of human CD27 as an antibody comprising the variable heavy chain of SEQ ID NO: 10 and the variable light chain of SEQ ID NO: 15; or binds the same epitope of human CD27 as an antibody comprising the variable heavy chain of SEQ ID NO:7 and the variable light chain of SEQ ID NO:8. 
     
     
         14 . An antibody or antigen binding fragment thereof, wherein, when bound to human CD27, binds at least one residue selected from the group consisting of Leu18, Asp34, Gln35, and Lys38 of SEQ ID NO: 19. 
     
     
         15 . The antibody or antigen binding fragment thereof of  claim 14 , wherein, when bound to human CD27, binds at least one residue selected from the group consisting of Gln35 and Lys38 of SEQ ID NO: 19. 
     
     
         16 . The antibody or antigen binding fragment of  claim 14 , wherein the antibody or antigen binding fragment thereof further binds one or more residues selected from the group consisting of Pro8, Glu9, His11, Lys17, His36, and Arg37 of SEQ ID NO: 19. 
     
     
         17 . The antibody or antigen binding fragment of  claim 14 , wherein the antibody or antigen binding fragment thereof further binds one or more residues selected from the group consisting of Glu9, Lys17, His36, and Arg37 of SEQ ID NO: 19. 
     
     
         18 . The antibody or antigen binding fragment thereof of  claim 14 , wherein the antibody or antigen binding fragment thereof binds residues Pro8, Glu9, His11, Lys17, Leu18, Asp34, Gln35, His36, Arg37 and Lys38 of SEQ ID NO: 19. 
     
     
         19 . The antibody or antigen binding fragment thereof of  claim 14 , wherein the antibody or antigen binding fragment thereof binds residues Glu9, Lys17, Leu18, Asp34, Gln35, His36, Arg37 and Lys38 of SEQ ID NO: 19. 
     
     
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         21 . The antibody or antigen binding fragment of  claim 3 , which is a humanized antibody comprising two heavy chains and two light chains, and is an IgG isotype. 
     
     
         22 . The antibody or antigen binding fragment of  claim 3 , which is an antibody of the IgG1 isotype. 
     
     
         23 . The antibody or antigen binding fragment of  claim 3 , which is an antibody of the IgG4 isotype. 
     
     
         24 . The antibody or antigen binding fragment of  claim 3 , wherein the antibody comprises the heavy chain constant domain of SEQ ID NO: 30. 
     
     
         25 . The antibody or antigen binding fragment of  claim 3 , wherein the antibody comprises the heavy chain constant domain of SEQ ID NO: 28. 
     
     
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         27 . The antibody or antigen binding fragment of  claim 3 , wherein the antibody or antigen binding fragment thereof comprises a glycosylation pattern characteristic of expression by a mammalian cell. 
     
     
         28 . The antibody or antigen binding fragment of  claim 3 , wherein the antibody or antigen binding fragment thereof comprises a glycosylation pattern characteristic of expression by a CHO cell. 
     
     
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