PD-L1-specific antibodies and methods of using the same
Inventors
Belk, Jonathan • SHARKEY, Nathan J. • Gorelik, Leonid
Assignees
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Publication Number
US-11834505-B2
Publication Date
2023-12-05
Expiration Date
Abstract
The present disclosure relates generally to antibodies and functional binding fragments thereof that bind to programmed death-ligand 1 (PD-L1). In particular, the disclosed antibodies and fragments bind to human PD-L1 and comprise novel complementary determining regions (CDRs) also disclosed herein. Finally, the present disclosure relates to administering the disclosed antibodies and fragments to subjects with cancer, thereby treating or slowing the progression or proliferation of the cancer.
Core Innovation
The invention relates to PD-L1-binding human antibodies and fragments that are defined by specific heavy-chain and light-chain complementarity determining regions. The antibody comprises a heavy chain with CDRH1 comprising any one of SEQ ID NOs: 2, 3, 4, 5, 6, or 7, a CDRH2 comprising any one of SEQ ID NOs: 8, 9, 10, 11, 12, 13, or 14, and a CDRH3 comprising SEQ ID NO: 15. The antibody also comprises a light chain with CDRL1 comprising SEQ ID NO: 20, a CDRL2 comprising SEQ ID NO: 21, and a CDRL3 comprising any one of SEQ ID NOs: 22, 75, or 76.
In addition, the document describes variants in which the heavy chain comprises any one of SEQ ID NOs: 36, 37, 38, 39, 40, or 41 and the light chain comprises SEQ ID NO: 42. The claimed binding target is human programmed death-ligand 1 (PD-L1), and the compositions are used for treating cancer. The document further describes functional attributes associated with PD-L1 binding, including blocking PD-L1 interactions with PD-1 and/or B7.1 and prevention of PD-1-mediated T-cell inhibition.
The patent text also describes exemplars with example antibody sequences (including CDR tables) and functional measurement readouts, including high affinity to human PD-L1 and PD-L1/PD-1 binding inhibition. Functional activity is described through antibody dependent cellular cytotoxicity (ADCC) and antitumor activity, and the document describes immunoblockade and immune activation readouts such as IFN-γ induction and a PD-L1/B7.1 inhibition reporter assay.
The disclosed therapeutic scope includes pharmaceutical compositions and methods of cancer treatment. The document describes treating cancer types including lung cancer, melanoma, renal cell carcinoma (RCC), head and neck, bladder cancer, and broader cancer categories. It further describes that combination therapy may be used, including combination with additional therapeutics such as CAR-T, other tumor-targeting antibodies, and immune potentiators (including anti-GITR/OX40/CD137) and small-molecule inhibitors.
Claims Coverage
The document includes two independent claims that both cover methods of treating cancer by administering a human PD-L1-binding antibody or fragment with specified heavy- and light-chain sequence-defined CDRs (SEQ ID NO constraints). Across the independent claims, the inventive features are primarily the PD-L1 binding antibody definition by CDR SEQ ID selections and the association with listed cancer indications.
Cdr-defined human PD-L1-binding antibody for treating cancer
Administering to a subject with cancer an antibody or a fragment thereof that binds human programmed death-ligand 1 (PD-L1) and comprises a heavy chain comprising a CDR H1 comprising any one of SEQ ID NOs: 2, 3, 4, 5, 6, or 7, a CDRH2 comprising any one of SEQ ID NOs: 8, 9, 10, 11, 12, 13, or 14, and a CDRH3 comprising SEQ ID NO: 15; and a light chain comprising a CDRL1 comprising SEQ ID NO: 20, a CDRL2 comprising SEQ ID NO: 21; and CDRL3 comprising any one of SEQ ID NOs: 22, 75, or 76.
Specific heavy- and light-chain SEQ ID PD-L1-binding antibody for treating specified cancers
Administering to a subject with cancer an antibody or a fragment thereof that binds human programmed death-ligand 1 (PD-L1) and comprises a heavy chain comprising any one of SEQ ID NOs: 36, 37, 38, 39, 40, or 41 and a light chain comprising SEQ ID NO: 42, wherein the cancer is lung cancer, melanoma, renal cell carcinoma (RCC), head and neck cancer, or bladder cancer.
The claim coverage centers on PD-L1-binding antibodies or fragments defined by enumerated SEQ ID NOs for heavy-chain and light-chain CDR regions. One independent claim provides a broader CDR-set definition for the antibody, and the other independent claim ties a specific set of heavy-chain SEQ ID NOs with a fixed light-chain SEQ ID NO to treatment of the listed cancer types.
Stated Advantages
High affinity to human PD-L1.
ADCC and antitumor activity.
Blocking of PD-L1 interactions with PD-1 and/or B7.1.
Prevention of PD-1-mediated T-cell inhibition.
Induction of IFN-γ.
Documented Applications
Methods of treating cancer in a subject using an antibody or fragment that binds human PD-L1, including lung cancer (including NSCLC), melanoma, renal cell carcinoma (RCC), head and neck cancer, and bladder cancer.
Cancer treatment using pharmaceutical compositions comprising the PD-L1-binding antibodies or fragments.
Combination therapy for cancer, including combination with CAR-T, other tumor-targeting antibodies, immune potentiators such as anti-GITR/OX40/CD137, and small-molecule inhibitors.
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