Anti-ROR1 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-11518815-B2
Publication Date
2022-12-06
Expiration Date
Abstract
The application provides anti-ROR1 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 invention relates to isolated monoclonal antibodies having a binding specificity to human ROR1. The disclosed antibody embodiments include a light chain comprising SEQ ID NO:76 and a heavy chain comprising SEQ ID NO:80, with associated complementarity determining regions and sequence listings.
The sequence listings annotate complementarity determining regions within the antibody variable regions, including CDR1, CDR2, and CDR3 assignments corresponding to SEQ ID NO:76 and SEQ ID NO:80. The content also supports embodiments defined by humanized light and heavy chain sequences, including full-length amino acid sequences and associated nucleotide sequences.
The document further describes functional immunomodulatory properties associated with the anti-ROR1 antibody, including enhanced T-cell activation such as increased T-cell proliferation, IFN-gamma, and IL-2, modulation of immunosuppressive cells including regulatory (Treg) cells, reversal of immunosuppressive cell effects, and binding performance characterizations using Kd and off-rate assessment. It additionally describes nucleic acids and expression system components used to produce the antibodies, immuno-conjugates comprising linkers and drug, imaging, or toxin payload options, pharmaceutical compositions comprising the antibody and pharmaceutically acceptable carriers, and cancer treatment contexts for ROR1-expressing malignancies.
Claims Coverage
The document includes two independent claims that define isolated monoclonal antibodies binding to human ROR1. The claim coverage centers on two inventive feature groupings: specific light and heavy chain sequence identities, and specific CDR compositions using SEQ ID references.
Human ROR1-binding mAb with SEQ ID-defined heavy and light chains
An isolated mAb having a binding specificity to human ROR1, comprising a light chain comprising SEQ ID NO:76 and a heavy chain comprising SEQ ID NO:80.
Human ROR1-binding mAb defined by CDR sets from SEQ ID NO:76 and SEQ ID NO:80
An isolated mAb having a binding specificity to human ROR1, wherein the isolated mAb comprises complementarity determining region (CDR)1, CDR2, and CDR3 of SEQ ID NO:76 and CDR1, CDR2, and CDR3 of SEQ ID NO:80.
Overall claim coverage defines isolated anti-ROR1 antibodies using explicit sequence-based requirements, including light and heavy chains with SEQ ID NO:76 and SEQ ID NO:80 and CDR1, CDR2, and CDR3 assignments from SEQ ID NO:76 and SEQ ID NO:80.
Stated Advantages
Enhanced T-cell activation, including increased T-cell proliferation, IFN-gamma, and IL-2.
Reversal of immunosuppressive cell effects, including modulation of regulatory (Treg) cells.
Inhibiting ROR1 activity and inducing apoptosis are stated functional biological properties.
Documented Applications
Cancer treatment context for ROR1-expressing malignancies.
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