ILT7 binding molecules and methods of using the same
Inventors
Vousden, Katherine Ann • DOUTHWAITE, Julie Ann • DAMSCHRODER, Melissa Marie • SANJUAN, Miguel Angel
Assignees
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Publication Number
US-11673950-B2
Publication Date
2023-06-13
Expiration Date
Abstract
The present invention is directed to ILT7 binding molecules, e.g., anti-ILT7 antibodies, and methods for treating or preventing conditions and diseases associated with ILT7-expressing cells such as autoimmune diseases.
Core Innovation
The disclosed content describes ILT7 (LIRA4/LILRA4/CD85g) biology and the rationale for ILT7 targeting in autoimmune disease. It focuses on administering an anti-ILT7 antibody to a subject in need thereof, where the antibody binds ILT7-expressing cells and is used to reduce inflammation-associated disease outcomes.
The anti-ILT7 antibody is defined by Complementarity-Determining Regions (CDRs) and specified amino acid sequences. In particular, the antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs:203, 204, 205, 208, 209, and 210, respectively, and may further include defined VH and VL sequence requirements including SEQ ID NO:202 and SEQ ID NO:207.
The content links ILT7 targeting to functional outcomes associated with interferon-alpha and plasmacytoid dendritic cells (pDCs). Treatment effectiveness is determined by detecting a reduced level of interferon-alpha or reduced pDCs after administering, and the content also discusses suppression of IFN-alpha release from PBMCs/pDCs and ADCC against ILT7-expressing cells.
The disclosed content further includes ILT7 polypeptide expression assays and characterization of anti-ILT7 antibody binding and function. It describes immunoassays and non-immunoassays, binding and affinity measurements, kinetic profiling, epitope mapping, and in vivo pDC depletion in cynomolgus monkeys with assessment of anti-drug antibodies (ADA) effects.
Claims Coverage
The consolidated content includes two independent claims. One claim covers treating a disease associated with ILT7-expressing cells that comprises inflammation using an anti-ILT7 antibody defined by specific CDR sequences and assessing effectiveness by reduced interferon-alpha or pDC levels after administration. The second independent claim covers reducing interferon-alpha and/or pDCs in a primate by administering an anti-ILT7 antibody with VH and VL defined by SEQ ID NO:202 and SEQ ID NO:207.
Cdr-defined anti-ilt7 antibody for treating inflammation-associated disease
A method of treating a disease associated with ILT7-expressing cells that comprises inflammation, comprising administering an effective amount of an anti-ILT7 antibody to a subject in need thereof, wherein the ILT7 antibody comprises CDRs HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs:203, 204, 205, 208, 209, and 210, respectively, and wherein treatment is effective as determined by detecting a reduced level of interferon-alpha or plasmacytoid dendritic cells (pDCs) in the subject after administering.
Seq id no:202/seq id no:207 vh/vl antibody for reducing interferon-alpha or pDCs in primates
A method of reducing the level of interferon-alpha or plasmacytoid dendritic cells (pDCs), the method comprising administering an effective amount of an anti-ILT7 antibody to a primate subject in need thereof, wherein the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein the VH and VL regions comprise an amino acid sequence comprising SEQ ID NO:202 and SEQ ID NO:207, respectively.
Across the independent claims, the core inventive coverage centers on administering an anti-ILT7 antibody that is defined by specified ILT7-binding sequence features (CDRs or VH/VL defined by SEQ ID NOs) and achieving measured reductions in interferon-alpha or plasmacytoid dendritic cells (pDCs) after administration, with the second independent claim specifying use in a primate subject.
Stated Advantages
Reduces the level of interferon-alpha or plasmacytoid dendritic cells (pDCs) after administering the anti-ILT7 antibody.
Suppresses IFN-alpha release from PBMCs/pDCs.
Enables ADCC against ILT7-expressing cells.
Treatment effectiveness is determined by detecting a reduced level of interferon-alpha or plasmacytoid dendritic cells (pDCs) after administering.
Reduction of the level of interferon-alpha and/or plasmacytoid dendritic cells (pDCs) in a primate subject.
Documented Applications
Therapeutic or prophylactic treatment of autoimmune diseases involving ILT7-expressing cells, including systemic lupus erythematosus and chronic rheumatism.
Discussion of ILT7 targeting in autoimmune disease contexts that include systemic lupus erythematosus and chronic rheumatism, and mentions psoriasis as an autoimmune disease context.
Treating a disease associated with ILT7-expressing cells that comprises inflammation, as determined by reduced interferon-alpha or pDC levels after administering the anti-ILT7 antibody.
Reducing the level of interferon-alpha or plasmacytoid dendritic cells (pDCs) in a primate subject by administering an anti-ILT7 antibody with defined VH and VL sequences.
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