Anti-cd40 antibodies
AssigneeBoehringer Ingelheim International GmbH
InventorsRachel Rebecca Barrett, Scott Ronald Brodeur, Keith Canada, Tobias Litzenburger, Sanjaya Singh
Life of this patent
Estimating the term…
Abstract
The present invention relates to new humanized antagonistic anti-CD40 antibodies and therapeutic and diagnostic methods and compositions for using the same.
Claims49
1-4. (canceled)
A humanized antibody, wherein said antibody comprises a heavy chain and a light chain, wherein the heavy chain sequence and light chain sequence are selected from the group consisting of:
- a) a heavy chain CDR1 sequence selected from the group consisting of SEQ ID NO:
- 9 through SEQ ID NO:11, a heavy chain CDR2 sequence selected from the group consisting of SEQ ID NO:12 through SEQ ID NO:15, and a heavy chain CDR3 sequence selected from the group consisting of SEQ ID NO:16 through SEQ ID NO:17;
- and
- b) the light chain CDR1 sequence has a sequence selected from the group consisting of SEQ ID NO:18 through SEQ ID NO:21, a light chain CDR2 sequence of SEQ ID NO:22 through SEQ ID NO:23, and a light chain CDR3 sequence selected from the group consisting of SEQ ID NO:24 through SEQ ID NO:25.
A humanized monoclonal antibody or antibody fragment having a heavy chain variable domain and a light chain variable region comprising the amino acid sequences of SEQ ID NO:27 and SEQ ID NO:26, respectively;
- SEQ ID NO:28 and SEQ ID NO:26, respectively;
- SEQ ID NO:29 and SEQ ID NO:26, respectively;
- SEQ ID NO:30 and SEQ ID NO:26, respectively;
- SEQ ID NO:32 and SEQ ID NO:31, respectively;
- SEQ ID NO:33 and SEQ ID NO:31, respectively;
- SEQ ID NO:34 and SEQ ID NO:31, respectively;
- SEQ ID NO:35 and SEQ ID NO:31, respectively;
- SEQ ID NO:37 and SEQ ID NO:36, respectively;
- SEQ ID NO:38 and SEQ ID NO:36, respectively;
- SEQ ID NO:39 and SEQ ID NO:36, respectively;
- SEQ ID NO:40 and SEQ ID NO:
- 36, respectively.
An isolated antibody or antigen-binding fragment that specifically binds to human CD40, comprising:
- a) a humanized heavy chain variable domain comprising a framework region having an amino acid sequence at least 90% identical to the amino acid sequence of the framework region of the human variable domain heavy chain amino acid sequence of SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34 or SEQ ID NO:35, and comprising a light chain amino acid sequence at least 90% identical to a corresponding light chain variable sequence of SEQ ID NO:31;
- or
- b) a humanized heavy chain variable domain comprising a framework region having an amino acid sequence at least 90% identical to the amino acid sequence of the framework region of the human variable domain heavy chain amino acid sequence of SEQ ID NO:
- 37, SEQ ID NO:38;
- SEQ ID NO:39 or SEQ ID NO:
- 40, and comprising a light chain amino acid sequence at least 90% identical to a corresponding light chain sequence of SEQ ID NO:36.
A humanized monoclonal antibody or antigen binding fragment of an antibody wherein said antibody or antigen binding fragment of the antibody specifically binds to human CD40 having an antagonistic activity IC50 of less than 1 nM and has no agonism up to 100 μg/ml in B cell proliferation and wherein said antibody or antigen binding fragment of the antibody is further characterized in that the antibody or antigen binding fragment of the antibody has an in vivo half-life in non-human primates that is at least 10 days;
- and wherein said antibody or antigen binding fragment of the antibody optionally has a half-life in cynomolgus monkeys of greater than 8 days at a dose of less than 30 mg/kg.
An isolated polynucleotide encoding a heavy chain variable region amino acid sequence or a light chain variable region, wherein the heavy chain variable region amino acid sequence comprises any of SEQ ID NO:
- 1 to 4, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:
- 29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:
- 40, SEQ ID NO:
- 42, SEQ ID NO:
- 44, SEQ ID NO:
- 46, SEQ ID NO:
- 48, SEQ ID. NO. 50, SEQ ID NO:
- 53, SEQ ID NO:
- 57, SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65, SEQ ID NO:
- 66, SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, or SEQ ID NO:
- 73;
- and light chain variable region amino acid sequence comprises any of SEQ ID NO:
- 5 to SEQ ID NO:8, SEQ ID NO:26, SEQ ID NO:31, SEQ ID NO:36, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:74, SEQ ID NO:75, or SEQ ID NO:76.
A humanized monoclonal antibody or antigen binding fragment comprising a heavy chain domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, or SEQ ID NO:40, and a light chain domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:26, SEQ ID NO:31 or SEQ ID NO:36.
A humanized monoclonal antibody or antigen binding fragment comprising a heavy chain domain that is at least 95% identical to the amino acid sequence of SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, or SEQ ID NO:40, and a light chain domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:26, SEQ ID NO:31 or SEQ ID NO:36.
A humanized monoclonal antibody or antigen binding fragment comprising a heavy chain variable domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 1 to 4, SEQ ID NO:
- 42, SEQ ID NO:
- 44, SEQ ID NO:
- 46, SEQ ID NO:
- 48, SEQ ID NO:
- 53, SEQ ID NO:
- 57, SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65, SEQ ID NO:
- 66, SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, or SEQ ID NO:
- 73, and a light chain variable domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 5 to SEQ ID NO:8, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:74, SEQ ID NO:75, or SEQ ID NO:76.
An isolated anti-CD40 antibody that binds the same epitope on CD40 as an antibody comprising a heavy chain domain that comprises the amino acid sequence of SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39 or SEQ ID NO:40, and a light chain domain that comprises the amino acid sequence of SEQ ID NO:26, SEQ ID NO:31 or SEQ ID NO:36.
An isolated polynucleotide encoding an antibody or antigen binding fragment comprising a heavy chain domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, or SEQ ID NO:40, and a light chain domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:26, SEQ ID NO:31 or SEQ ID NO:36.
An isolated polynucleotide encoding an antibody or antigen binding fragment comprising a heavy chain domain that is at least 95% identical to the amino acid sequence of SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, or SEQ ID NO:40, and a light chain domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:26, SEQ ID NO:31 or SEQ ID NO:36.
An isolated polynucleotide encoding an antibody or antigen binding fragment comprising a heavy chain variable domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 1 to 4, SEQ ID NO:
- 42, SEQ ID NO:
- 44, SEQ ID NO:
- 46, SEQ ID NO:
- 48, SEQ ID NO:
- 53, SEQ ID NO:
- 57, SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65, SEQ ID NO:
- 66, SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, or SEQ ID NO:
- 73, and a light chain variable domain that is at least 90% identical to the amino acid sequence of SEQ ID NO:
- 5 to SEQ ID NO:8, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:74, SEQ ID NO:75, or SEQ ID NO:76.
Dependencies are inferred from the claim text.