Polynucleotides encoding anti-PD-L1 antibodies
Inventors
KOWANETZ, Marcin • Koeppen, Hartmut • BOYD, Zachary • LIAO, Zhiming • Zhu, YiFei • Vennapusa, Bharathi • Roche, Patrick C.
Assignees
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Abstract
The invention provides programmed death-ligand 1 (PD-L1) antibodies and methods of using the same.
Core Innovation
The patent describes isolated nucleic acids that encode antibody variable domains. The heavy chain variable domain (VH) is defined by specific hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) comprising the amino acid sequences SNGLT (SEQ ID NO: 2), TINKDASAYYASWAKG (SEQ ID NO: 3), and IAFKTGTSI (SEQ ID NO: 4).
The patent also defines isolated nucleic acids encoding the antibody light chain variable domain (VL) by specific hypervariable regions (HVR-L1, HVR-L2, and HVR-L3) comprising the amino acid sequences QASESVYSNNYLS (SEQ ID NO: 9), LASTLAS (SEQ ID NO: 10), and IGGKSSSTDGNA (SEQ ID NO: 11). The claims further specify framework regions (FR-H1 to FR-H4 and FR-L1 to FR-L4) with defined amino acid sequences and sequence identity relative to specified sequences.
In addition to VH-only and VL-only nucleic acid encodings, the patent provides isolated nucleic acids encoding both an antibody VH and an antibody VL. The combination defines the VH by the same specified HVR-H1, HVR-H2, and HVR-H3 and defines the VL by the same specified HVR-L1, HVR-L2, and HVR-L3. Claim scope is extended to constructs including a vector containing the isolated nucleic acid and a host cell including the vector.
Claims Coverage
The independent claims cover isolated nucleic acids encoding antibody variable domains with specified hypervariable-region amino acid sequences, plus dependent refinements that add framework-region sequence specifications, sequence-identity constraints, and constructs comprising vectors and host cells. The main inventive features are the defined HVR amino acid sequences for VH and/or VL, and the paired/identity-based refinement options for the VH and/or VL.
Specified VH hypervariable regions
An isolated nucleic acid encoding an antibody heavy chain variable domain (VH), wherein the VH comprises HVR-H1 comprising the amino acid sequence SNGLT (SEQ ID NO: 2), HVR-H2 comprising the amino acid sequence TINKDASAYYASWAKG (SEQ ID NO: 3), and HVR-H3 comprising the amino acid sequence IAFKTGTSI (SEQ ID NO: 4).
Specified VL hypervariable regions
An isolated nucleic acid encoding an antibody light chain variable domain (VL), wherein the VL comprises HVR-L1 comprising the amino acid sequence QASESVYSNNYLS (SEQ ID NO: 9), HVR-L2 comprising the amino acid sequence LASTLAS (SEQ ID NO: 10), and HVR-L3 comprising the amino acid sequence IGGKSSSTDGNA (SEQ ID NO: 11).
Paired VH and VL hypervariable regions
An isolated nucleic acid encoding an antibody heavy chain variable domain (VH) and an antibody light chain variable domain (VL), wherein the VH comprises HVR-H1 comprising the amino acid sequence SNGLT (SEQ ID NO: 2), HVR-H2 comprising the amino acid sequence TINKDASAYYASWAKG (SEQ ID NO: 3), and HVR-H3 comprising the amino acid sequence IAFKTGTSI (SEQ ID NO: 4); and wherein the VL comprises HVR-L1 comprising the amino acid sequence QASESVYSNNYLS (SEQ ID NO: 9), HVR-L2 comprising the amino acid sequence LASTLAS (SEQ ID NO: 10), and HVR-L3 comprising the amino acid sequence IGGKSSSTDGNA (SEQ ID NO: 11).
Across the independent claims, the coverage is anchored by antibody variable-domain definitions through specified HVR amino acid sequences for the VH and/or VL, with dependent refinements to include defined framework regions, sequence-identity constraints to named sequences, and extensions to vectors and host cells containing the isolated nucleic acids.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Diagnostic PD-L1 detection using immunohistochemistry (IHC), immunofluorescence (IF), flow cytometry, ELISA, and immunoblot/Western blot.
Patient selection and predicting the likelihood of response to anti-cancer therapies involving the PD-1 axis binding antagonist concept.
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