Anti-4-1BB antibodies and methods of making and using thereof
Inventors
Olsen, Ole • Xia, Dong • JELLYMAN, David • Kovacevich, Brian • Brady, Bill • RENSHAW, Blair • Gao, Zeren • Zhu, Yi
Assignees
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Publication Number
US-11987635-B2
Publication Date
2024-05-21
Expiration Date
Abstract
The application provides anti-4-1BB monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.
Core Innovation
The invention provides an isolated monoclonal antibody (mAb) or an antigen-binding fragment thereof that binds specifically to human or cynomolgus 4-1BB (CD137). The antibodies are defined by variable light chain and variable heavy chain sequence content, including SEQ ID NO:244 and SEQ ID NO:248, and include complementarity-determining regions (CDRs) as part of the defined antigen-binding components.
The disclosure further defines antigen-binding fragments by CDR composition, including specified light-chain and heavy-chain CDR1, CDR2, and CDR3 amino-acid segment ranges taken from the referenced sequences. The described sequences also include full-length sequences with human constant domains, including human gamma-1 constant domain and human kappa constant domain, and are presented in multiple engineered formats.
The antibodies and fragments are presented in therapeutic compositions comprising a pharmaceutically acceptable carrier and optionally including radioisotope, radionuclide, toxin, therapeutic agent, and/or chemotherapeutic agent payload components. The disclosure states use for cancer and other T-cell dysfunction disorders, including enhancing T-cell function and cell-mediated immune responses.
Claims Coverage
The document includes two independent claims. Collectively, they define 4-1BB-binding isolated monoclonal antibodies or antigen-binding fragments with two inventive features: specified variable light/heavy chain sequence assignments and specified CDR amino-acid segment inclusion for light and heavy chains.
Specific 4-1BB-binding antibody variable light and heavy chains
An isolated monoclonal antibody (mAb) or antigen-binding fragment thereof that binds specifically to human or cynomolgus 4-1BB, comprising a variable light chain comprising SEQ ID NO:244 and a variable heavy chain comprising SEQ ID NO:248.
CDR-defined 4-1BB-binding light and heavy chains
An isolated mAb or antigen-binding fragment thereof having a binding specificity to human or cynomolgus 4-1BB, comprising a light chain and a heavy chain, wherein the isolated mAb or antigen-binding fragment thereof comprises amino acids 24-34 of SEQ ID NO:244 as CDR1, amino acids 50-56 of SEQ ID NO:244 as CDR2, and amino acids 89-101 of SEQ ID NO:244 as CDR3 of the light chain, and amino acids 30-34 of SEQ ID NO:248 as CDR1, amino acids 49-64 of SEQ ID NO:248 as CDR2, and amino acids 97-104 of SEQ ID NO:248 as CDR3 of the heavy chain.
Selected mAb format including humanized, chimeric, or multispecific antibodies
The isolated monoclonal antibody is specified as an IgG, humanized antibody, chimeric antibody, recombinant antibody, bispecific antibody, tri-specific antibody, or multi-specific antibody.
Selected antigen-binding fragment type
The antigen-binding fragment is one of Fv, Fab, F(ab')2, scFV, or scFV2.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition includes the isolated monoclonal antibody (mAb) or an antigen-binding fragment thereof together with a pharmaceutically acceptable carrier.
Optional payload and therapeutic or chemotherapeutic agents in the composition
The pharmaceutical composition is further formulated with one or more of a radioisotope, a radionuclide, a toxin, a therapeutic agent, and/or a chemotherapeutic agent.
Across the independent claims, the claim coverage centers on 4-1BB-binding isolated mAbs or antigen-binding fragments defined either by specified variable light and heavy chains (SEQ ID NO:244 and SEQ ID NO:248) or by explicit residue-range CDR1/CDR2/CDR3 inclusion for both the light and heavy chains, with dependent claims extending to antibody formats, fragment categories, and pharmaceutical compositions.
Stated Advantages
Enhancing T-cell function and cell-mediated immune responses for treating cancer and other T-cell dysfunction disorders.
Documented Applications
Treating cancer and other T-cell dysfunction disorders by enhancing T-cell function and cell-mediated immune responses.
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