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-11072652-B2
Publication Date
2021-07-27
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 invention relates to immunoglobulin-like transcript 7 (ILT7) and provides anti-ILT7 antibodies comprising defined Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The disclosed antibody CDRs are specified by amino acid sequences of SEQ ID NOs:203, 204, 205, 208, 209, and 210, respectively, and the disclosure further includes afucosylated anti-ILT7 antibody formats and human antibody constant domains.
The disclosed anti-ILT7 antibodies are also defined by structural antibody features such as a heavy chain variable region (VH) and a light chain variable region (VL) with specified amino acid sequences. In some embodiments, the antibodies comprise a human IgG1 constant domain and a human lambda constant domain, and the invention frames binding and functional concepts for ILT7, including inhibition of IFN-alpha release from plasmacytoid dendritic cells (pDCs).
The invention additionally encompasses binding-focused and functional outcomes associated with ILT7 targeting, including decreasing interferon (IFN)-alpha release from plasmacytoid dendritic cells (pDC) by contacting pDC with an anti-ILT7 antibody. The disclosure also supports embodiments involving afucosylated, human monoclonal anti-ILT7 antibodies, as well as polynucleotides encoding the antibodies and pharmaceutical composition embodiments.
Claims Coverage
The claim set presented includes three independent claims. The main coverage is directed to anti-ILT7 antibodies defined by precise CDR sequence identities, with further restriction to afucosylated, human monoclonal formats. Additional claim scope specifies human IgG1 and lambda constant domains and, in another embodiment, ties the antibody to specific VH and VL amino-acid sequences.
Sequence-defined anti-ilt7 antibody CDRs
An anti-ILT7 antibody comprising Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs:203, 204, 205, 208, 209, and 210, respectively.
Afucosylated human monoclonal anti-ilt7 with human igg1 and human lambda constant domains
An afucosylated, human, monoclonal anti-ILT7 antibody comprising Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and a human IgG1 constant domain and a human lambda constant domain, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs:203, 204, 205, 208, 209, and 210, respectively.
Afucosylated igg1 human monoclonal anti-ilt7 defined by vh and vl sequence identities
An afucosylated IgG1 human monoclonal anti-ILT7 antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises the amino acid of SEQ ID NO:202 and the light chain variable region comprises the amino acid of SEQ ID NO:207.
Overall, the claim coverage centers on anti-ILT7 antibodies characterized by specific CDR amino-acid sequences, with additional structural limitations including afucosylated format, human IgG1 and human lambda constant-domain elements in one independent claim, and specified VH and VL amino-acid sequences in another.
Stated Advantages
Decrease interferon (IFN)-alpha release from plasmacytoid dendritic cells (pDCs).
Decreasing interferon (IFN)-alpha release from plasmacytoid dendritic cells (pDC) by contacting the pDC with an anti-ILT7 antibody.
Documented Applications
Decreasing interferon (IFN)-alpha release from plasmacytoid dendritic cells (pDC) by contacting the pDC with an anti-ILT7 antibody.
ILT7 polypeptide expression assays and immunoassays, including immunodetection formats and antibody binding characterization approaches.
Use of polynucleotides encoding the anti-ILT7 antibodies (polynucleotide containing a nucleic acid encoding the anti-ILT7 antibody of claim 1).
Pharmaceutical compositions comprising the afucosylated IgG1 human monoclonal anti-ILT7 antibody.
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