Anti-CD3 antibodies and methods of making and using thereof
Inventors
Olsen, Ole • Tan, Phil • Xia, Dong • JELLYMAN, David • Kovacevich, Brian • Brady, Bill • RENSHAW, Blair • Gao, Zeren • Zhu, Yi
Assignees
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Publication Number
US-11535667-B2
Publication Date
2022-12-27
Expiration Date
Abstract
The applications provides the anti-CD3 monoclonal antibodies, antigen-binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to active CD3+ T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.
Core Innovation
The invention relates to isolated monoclonal antibodies and antigen-binding fragments having binding specificity to human CD3. The disclosed antibodies include an amino acid sequence as defined by SEQ ID NO: 56, and the antigen-binding fragments are described as part of the CD3-binding antibody formats.
The invention further defines CD3-binding performance and functional consequences of the antibodies. Binding performance is constrained by dissociation constant thresholds, and the antibodies are associated with T-cell activation, stimulation of an antibody response, and reversal of suppressive function of immunosuppressive T regulatory cells (Tregs).
The disclosed subject matter includes sequence-defined components and related biological materials. It recites CD3-binding IgG1 heavy chains and kappa light chains by specific amino acid sequences, including SEQ ID NO: 55 and SEQ ID NO: 51, as well as variable light-chain and variable heavy-chain sequences, including SEQ ID NO: 52 and SEQ ID NO: 56. The patent content also describes pharmaceutical composition concepts and drug-conjugate and immunoconjugate designs using linkers and drug payload classes.
Claims Coverage
The independent claims cover sequence-defined CD3-binding antibody molecules and related components. Across the independent-claim set, the inventive features are primarily sequence-defined antibody components with binding specificity to human CD3, with additional functional and affinity constraints appearing in dependent claims associated with the first independent claim.
Sequence-defined CD3-binding isolated monoclonal antibody or antigen-binding fragment
An isolated monoclonal antibody or antigen-binding fragment thereof having binding specificity to human CD3, wherein the isolated mAb or antigen-binding fragment comprises an amino acid sequence of SEQ ID NO: 56.
Kd-constrained human CD3 binding affinity
The isolated mAb or antigen-binding fragment binds human CD3 with a dissociation constant of no more than 70 nM.
Functional modulation of T cell activation and immunosuppressive function
The isolated mAb or antigen-binding fragment binds to CD3 with high affinity and thereby enhances T cell activation, stimulates antibody response, or reverses suppressive function of an immunosuppressive cell.
T regulatory cell as the immunosuppressive cell context
The immunosuppressive cell comprises a T regulatory cell.
Specified antigen-binding fragment formats
The isolated mAb or antigen-binding fragment includes a specified fragment format such as an Fv, Fab, F(ab′)2, scFv, scFv2, or a combination thereof.
Nucleic acid encoding the sequence-defined antibody or fragment
An isolated nucleic acid that encodes the specified isolated monoclonal antibody or its antigen-binding fragment.
Sequence-defined IgG heavy chain for human CD3-binding mAb
An IgG heavy chain for an isolated mAb having binding specificity to human CD3, comprising an amino acid sequence of SEQ ID NO: 55.
Sequence-defined kappa light chain for human CD3-binding mAb
A kappa light chain for an isolated mAb having binding specificity to human CD3, comprising an amino acid sequence of SEQ ID NO: 51.
Sequence-defined variable light chain for human CD3-binding mAb
A variable light chain for an isolated mAb having binding specificity to human CD3, comprising an amino acid sequence of SEQ ID NO: 52.
Sequence-defined variable heavy chain for human CD3-binding mAb
A variable heavy chain for an isolated mAb having binding specificity to human CD3, comprising an amino acid sequence of SEQ ID NO: 56.
Overall, the claim coverage centers on CD3-binding antibody molecules whose sequence identity is anchored to specific SEQ ID numbers, notably SEQ ID NO: 56, with further narrowing by quantitative Kd binding affinity, functional outcomes for T cell activation and immunosuppressive reversal, and specified antigen-binding fragment formats. Additional coverage recites sequence-defined heavy- and light-chain components for human CD3-binding monoclonal antibodies.
Stated Advantages
Enhances T cell activation.
Stimulates antibody response.
Reverses suppressive function of an immunosuppressive cell.
Binds human CD3 with a dissociation constant of no more than 70 nM.
Documented Applications
Therapeutic composition concepts are described, including pharmaceutical compositions and drug-conjugate or immunoconjugate designs with linkers and drug payload classes.
Use of CD3-binding antibodies is described in relation to T-cell activation, stimulation of an antibody response, and reversal of Treg suppressive function.
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