Antibodies to CD40

A chimeric or human monoclonal antibody or antigen-binding portion thereof that specifically binds to and activates human CD40, wherein said antibody or antigen-binding portion thereof comprises:

• a) a heavy chain comprising amino acid sequences of a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 from a heavy chain variable region;
• wherein said amino acid sequences of the heavy chain CDR1 and the heavy chain CDR2 are independently selected from a CDR1 and a CDR2 of a heavy chain variable region, respectively, wherein the sequence of said heavy chain variable region comprises no more than 18 amino acid changes from the amino acid sequence encoded by a germline VH 3-30+, 4-59, 1-02, 4.35 or 3-30.3 gene;
• wherein said amino acid sequence of the heavy chain CDR3 is from a CDR3 of a heavy chain variable region, wherein said heavy chain variable region is selected from the group consisting of
• i) a heavy chain variable region of an antibody selected from the group consisting of 3.1.1, 3.1.1 H-A78T, 3.1.1H-A78T-V88A-V97A, 7.1.2, 10.8.3, 15.1.1, 21.4.1, 21.2.1, 22.1.1, 22.1.1H-C109A, 23.5.1, 23.25.1, 23.28.1, 23.28.1H-D16E, 23.29.1 and 24.2.1;
• ii) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
• 2, 10, 18, 26, 34, 42, 50, 58, 66, 74 and 82, or a heavy chain variable region comprising an amino acid sequence from the heavy chain amino acid sequence selected from the group consisting of SEQ ID NOS:
• 90, 92, 96 and 98, or said amino acid sequence lacking a signal sequence;
• and
• iii) a heavy chain variable region encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
• 1, 9, 17, 25, 33, 41, 49, 57, 65, 73 and 81, or a heavy chain variable region comprising an amino acid sequence encoded by the heavy chain nucleic acid sequence selected from the group consisting of 89, 91, 95 and 97, or said encoded heavy chain variable region lacking a signal sequence;
• wherein the amino acid sequence of said heavy chain CDR3 may have up to two conservative amino acid substitutes and/or two non-conservative amino acid insertions, deletions or substitutions therefrom;
• or
• b) a light chain comprising amino acid sequences of a light chain CDR1, a light chain CDR2 and a light chain CDR3 from a light chain variable region,
• wherein said amino acid sequences of the light chain CDR1 and the light chain CDR3 are independently selected from CDR1 and a CDR3 of a light chain variable region, respectively, wherein the light chain variable region comprises no more than ten amino acid changes from the amino acid sequence encoded by a germline Vκ A3/A19, L5 or A27 gene;
• and
• wherein said amino acid sequence of the light chain CDR2 is from a light chain variable region, wherein said light chain variable region is selected from the group consisting of
• i) a light chain variable region of an antibody selected from the group consisting of 3.1.1, 3.1.L-L4M-L83V, 7.1.2, 10.8.3, 15.1.1, 21.4.1, 21.2.1, 22.1.1, 23.5.1, 23.25.1, 23.28.1, 23.28.1L-C92A, 23.29.1 and 24.2.1;
• ii) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
• 4, 12, 20, 28, 36, 44, 52, 60, 68, 76 and 84, or a light chain variable region comprising an amino acid sequence from the light chain amino acid sequence selected from the group consisting of SEQ ID NOS:
• 94 and 100, or said amino acid sequence lacking a signal sequence;
• and
• iii) a light chain variable region encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
• 3, 11, 19, 27, 35, 43, 51, 59, 67, 75 and 83, or a light chain variable region comprising an amino acid sequence encoded by the light chain nucleic sequence selected from the group consisting of SEQ ID NOS:
• 93 and 99, or said encoded light chain variable region lacking a signal sequence;
• wherein the amino acid sequence of said light chain CDR2 may have up to two conservative amino acid substitutes and/or two non-conservative amino acid insertions, deletions or substitutions therefrom.