ADDL receptor polypeptides, polynucleotides and host cells for recombinant production
Inventors
Jerecic, Jasna • Krafft, Grant A.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9217024-B2
Publication Date
2015-12-22
Expiration Date
Abstract
This invention provides a novel receptor expressed on neuronal cells in a developmentally-specific manner. Accordingly, this invention provides the amino acid sequences of selected portions of the receptor and polynucleotides encoding these portions as well as antibodies that bind to the polypeptide portions of the receptor. Compositions and methods for using the compositions are also provided.
Core Innovation
The invention provides antibodies that bind an amyloid β-derived diffusible ligand receptor polypeptide. The receptor polypeptide contains amino acid sequences selected from CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5), SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and HDSHIPLEDCR (SEQ ID NO: 7), and receptor polypeptide epitopes comprise non-contiguous binding-region epitopes.
The invention further provides antibodies that bind two binding regions of an amyloid β-derived diffusible ligand receptor polypeptide, where the two binding regions are non-contiguous and each binding region is selected from specified sequence sets. It also includes isolated antibody-peptide complexes in which the peptide specifically binds to the antibody, including cases where the polypeptide is the immunogen polypeptide used to raise the antibody.
The disclosure also addresses compositions and formulations that include the antibody with a carrier, including pharmaceutically acceptable carriers and solid supports. The disclosed antibody embodiments include diagnostic and therapeutic contexts for detecting or monitoring amyloid β-derived diffusible ligand receptor or receptor complex expression, with gene expression detection and protein detection described using immunoassays and related detection modalities.
Claims Coverage
The document includes six independent claims. Across these claims, the inventive features focus on antibody binding to enumerated amyloid β-derived diffusible ligand receptor polypeptide sequences or non-contiguous binding regions, isolated antibodies that inhibit binding of soluble amyloid β-derived diffusible ligand to a neural receptor, isolated antibody–peptide complexes, and compositions with carriers.
Antibody binding to enumerated ADDL receptor polypeptide sequences
An antibody that binds an amyloid β-derived diffusible ligand receptor polypeptide comprising amino acid sequences selected from CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5), SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and HDSHIPLEDCR (SEQ ID NO: 7).
Antibody binding to two non-contiguous ADDL receptor binding regions
An antibody that binds two binding regions of an amyloid β-derived diffusible ligand receptor polypeptide, the two binding regions being non-contiguous, wherein the first binding region is selected from CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5), SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and HDSHIPLEDCR (SEQ ID NO: 7), and wherein the second binding region is different from the first binding region and is selected from AVIMFANEDDIR (SEQ ID NO: 2), ASIDGFDQYFRSQTLANNR (SEQ ID NO: 3), ASIDGFDQYFR (SEQ ID NO: 4), CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5), SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and HDSHIPLEDCR (SEQ ID NO: 7).
Antibody binding to one or more enumerated ADDL receptor polypeptides with optional additional binding
An antibody that binds at least one amyloid β-derived diffusible ligand receptor polypeptide selected from CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5), SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and HDSHIPLEDCR (SEQ ID NO: 7), wherein the antibody optionally further binds to at least one polypeptide selected from AVIMFANEDDIR (SEQ ID NO: 2), ASIDGFDQYFRSQTLANNR (SEQ ID NO: 3), and ASIDGFDQYFR (SEQ ID NO: 4).
Isolated inhibiting antibody binding specified ADDL receptor polypeptides
An isolated antibody that inhibits binding of soluble amyloid β-derived diffusible ligand to a neural receptor and binds a polypeptide selected from a polypeptide comprising amino acid sequence CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5) and SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), a polypeptide comprising two non-contiguous binding regions comprising ASIDGFDQYFRSQTLANNR (SEQ ID NO: 3) and SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and a polypeptide comprising two non-contiguous binding regions comprising ASIDGFDQYFR (SEQ ID NO: 4) and HDSHIPLEDCR (SEQ ID NO: 7).
Isolated inhibitory antibodies binding one of three specified ADDL receptor polypeptides
An isolated antibody that inhibits binding of soluble amyloid β-derived diffusible ligand to a neural receptor and binds a polypeptide selected from CTENVPVTDFFVGPVCIIPK (SEQ ID NO: 5), SSVWDERHDSHIPLEDCR (SEQ ID NO: 6), and HDSHIPLEDCR (SEQ ID NO: 7).
Overall, the claims coverage centers on antibodies defined by binding to specific amyloid β-derived diffusible ligand receptor polypeptide amino acid sequences (SEQ ID NOs: 2-7) or by binding to two non-contiguous binding regions selected from specified sequence sets. Separate independent claims additionally define isolated antibodies that inhibit binding of soluble amyloid β-derived diffusible ligand to a neural receptor while binding the enumerated polypeptides.
Stated Advantages
Inhibits binding of soluble amyloid β-derived diffusible ligand to a neural receptor.
Documented Applications
Diagnostic and therapeutic uses for neurodegenerative disorders, including Alzheimer’s disease, Down’s syndrome, and MCI.
Assay/kits concepts and patient selection based on detection of the receptor and/or polynucleotides.
Interested in licensing this patent?