Anti-PD-1 antibodies and methods of making and using thereof
Inventors
Kovacevich, Brian • Xia, Dong • JENSEN, Anne E. • FALLEN, Jonathan K. • RENSHAW, Blair • Adamo, Jeffrey B. • Tan, Phil • Gao, Zeren • Zhu, Yi
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11466084-B2
Publication Date
2022-10-11
Expiration Date
Abstract
The application provides anti-PD-1 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 disclosure relates to anti-human PD-1 monoclonal antibodies that specifically bind human PD-1. The antibodies are defined by amino acid sequences provided as SEQ ID NO:52 and SEQ ID NO:56, including antigen-binding fragments having specified sequence homology to multiple SEQ IDs. The disclosed antibodies are configured to inhibit the PD-1/PD-L1 interaction and to drive immune functional effects on PD-1 signaling.
The disclosed antibodies are further described with functional properties including blocking binding of human PD-L1 to human PD-1 and enhancing T-cell activation. Functional outcomes described include T-cell proliferation and cytokine-related activity such as IFN-γ and IL-2. The disclosure also includes reversing suppressive or immunosuppressive function associated with immunosuppressive or regulatory cells, including T regulatory cells.
The disclosure covers multiple antibody formats and embodiments, including humanized, chimeric, and recombinant antibodies, and engineered antibody types such as IgG, including IgG1, and various fragment types. Multi-specific antibody configurations, including bispecific, trispecific, and multi-specific antibodies, are also included. In addition to the antibody itself, the disclosure includes nucleic acids, expression vectors, host cells, immuno-conjugates with drug/toxin or imaging payloads linked by linkers, pharmaceutical compositions, and methods of treating cancer involving PD-1-expressing cells.
Claims Coverage
The independent claim is directed to an isolated monoclonal antibody defined by two specified amino acid sequences. The coverage extends through dependent claims to functional properties tied to PD-1/PD-L1 interaction and immune activity, and to pharmaceutical compositions, immuno-conjugates, nucleic-acid/host-cell embodiments, and cancer treatment use, for a total of six inventive features.
Isolated anti-human PD-1 monoclonal antibody defined by SEQ IDs
An isolated mAb having binding specificity to human PD-1, comprising an amino acid sequence of SEQ ID NO:52 and an amino acid sequence of SEQ ID NO:56.
Functional PD-1/PD-L1 blockade and immune activation effects
An isolated monoclonal antibody defined by functional properties including high-affinity binding to human PD-1, blocking human PD-L1 binding to PD-1, enhancing T cell activation, stimulating an antibody response, reversing the suppressive function of an immunosuppressive cell, or combinations thereof.
Pharmaceutical composition with a pharmaceutically acceptable carrier
A pharmaceutical composition made with the isolated monoclonal antibody or its antigen-binding fragment plus a pharmaceutically acceptable carrier.
Cancer treatment by administering an effective amount of the anti-PD-1 mAb
A method for treating a subject’s cancer by administering an effective amount of the isolated monoclonal antibody where the cancer includes cells expressing PD-1.
Immuno-conjugate linked to a drug unit
An immuno-conjugate that includes an isolated monoclonal antibody linked to a drug unit selected from a cytotoxic agent or an immune regulatory reagent, or a combination thereof.
Host cell containing nucleic acid for production
A host cell that contains the nucleic acid of the related claim, where the host cell can be either a prokaryotic or a eukaryotic cell.
Overall, the claim coverage centers on an isolated anti-human PD-1 mAb defined by specific amino acid sequences, with dependent coverage extending to PD-1/PD-L1 functional blockade and immune activation effects, plus pharmaceutical composition, cancer treatment, immuno-conjugate, and nucleic-acid/host-cell embodiments.
Stated Advantages
Blocking binding of human PD-L1 to human PD-1.
Enhancing T cell activation, including T-cell proliferation.
Stimulating immune-related functional activity including IFN-γ and IL-2.
Reversing the suppressive function of an immunosuppressive cell, including T regulatory cells.
Documented Applications
Treating a subject’s cancer by administering an effective amount of the isolated monoclonal antibody, where the cancer includes cells expressing PD-1.
Interested in licensing this patent?