Anti-PD-L1 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
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Publication Number
US-11560431-B2
Publication Date
2023-01-24
Expiration Date
Abstract
The application provides the anti-PD-L1 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 patent relates to isolated monoclonal antibodies and antigen-binding fragments having binding specificity to human PD-L1. The antibodies and fragments are defined by specified variable light chain sequences and specified variable heavy chain sequences, including multiple sets of SEQ ID NO combinations for the variable light chain and variable heavy chain.
In additional embodiments, the antibodies are defined by complementarity determining region (CDR)1, CDR2, and CDR3 sequence sets associated with SEQ ID NO pairs. The patent further describes antigen-binding fragments and related antibody formats, including IgG and fragment types, in connection with binding specificity to human PD-L1.
The document also addresses uses and formulations for these PD-L1-binding antibodies and fragments, including immuno-conjugates where a drug or imaging agent is linked via a linker, pharmaceutical compositions including a pharmaceutically acceptable carrier, and methods for treating cancer that includes cells expressing PD-L1.
Claims Coverage
The independent claims cover isolated mAbs or antigen-binding fragments that specifically bind human PD-L1, with claim scope defined by SEQ ID NO-defined variable chain sequences and, in a separate independent claim, by CDR1/CDR2/CDR3 SEQ ID NO-defined sets. The claim set also includes Kd and sequence-identity refinements, and further encompasses nucleic acids, pharmaceutical compositions, and administration for cancer treatment.
Variable chain SEQ ID NO-defined anti-PD-L1 monoclonal antibodies
An isolated monoclonal antibody or antigen-binding fragment thereof having binding specificity to human PD-L1, wherein the variable light chain and variable heavy chain comprise specified SEQ ID NO combinations.
CDR1/CDR2/CDR3 SEQ ID NO-defined anti-PD-L1 antibodies
An isolated monoclonal antibody or antigen-binding fragment thereof having binding specificity to human PD-L1, wherein the CDR1, CDR2, and CDR3 sets are defined by specified SEQ ID NO pairs.
Kd threshold anti-PD-L1 affinity
An isolated monoclonal antibody or antigen-binding fragment that binds PD-L1 with a dissociation constant of no more than 70 nM.
IgG heavy and kappa light chain sequence identity constraints
An isolated monoclonal antibody or antigen-binding fragment comprising specific IgG heavy chain and kappa light chain sequences that each share at least 98% sequence identity with one of several SEQ ID NO pairs.
Encoding nucleic acid for the PD-L1-binding antibody
An isolated nucleic acid that encodes the isolated monoclonal antibody or antigen-binding fragment.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition that includes the isolated monoclonal antibody or antigen-binding fragment along with a pharmaceutically acceptable carrier.
Treating cancer with PD-L1 expressing cells by administration
A method for treating a subject’s cancer by administering an effective amount of an isolated monoclonal antibody or an antigen-binding fragment thereof, where the cancer includes cells expressing PD-L1.
Overall, the claims define PD-L1-binding isolated antibodies and antigen-binding fragments primarily by SEQ ID NO-defined variable light and variable heavy chain sequences or by specific SEQ ID NO-defined CDR sets. The claim set also includes Kd affinity thresholds and high sequence identity constraints, and further encompasses nucleic acids, pharmaceutical compositions, and administration for treating cancer involving PD-L1-expressing cells.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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