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AssigneeOssianix, Inc.
InventorsKrzysztof Bartlomiej Wicher, Jaroslaw Michal Szary, Julia Lynn Rutkowski, Fabrizio Comper, Pawel Stocki
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The present invention relates to CD98hc binding moieties with high specificity and with ability to cross the blood brain barrier (BBB). Such moieties may be used alone or as components in specific conjugates that target the amino acid transporter complexes formed with a light chain and CD98hc. The invention relates more specifically to VNAR single chain antibodies derived from nurse shark that bind to CD98hc, compounds and compositions comprising a CD98hc-specific binding moiety, diagnostic and therapeutic methods of use in vitro or in vivo, e.g., to diagnose, treat and/or prevent a pathological condition, disorder or disease in which it is beneficial to deliver a heterologous biomolecule across the blood brain barrier by association with a CD98hc-specific VNAR binding moiety. The invention also includes Type IV semi-synthetic VNAR libraries derived from shark VNARs for selection of binding moieties that specifically bind to a molecular or cellular target of interest.
An isolated CD98hc-specific binding moiety comprising a VNAR domain capable of specifically binding to human CD98hc and murine CD98hc, wherein said VNAR domain is represented by the formula, from N to C terminus,
A nucleic acid molecule encoding at least one binding moiety or a conjugate of any one of the preceding claims.
A method of targeting delivery of a payload to brain parenchymal tissue in a mammal which comprises administering a CD98hc binding moiety or conjugate of any one of the preceding claims.
Use of a CD98hc binding moiety or conjugate of any one of the preceding claims for targeting delivery of a payload to brain parenchymal tissue in a mammal.
A kit for detecting or quantifying CD98hc in a sample which comprises at least one CD98hc binding moiety or conjugate of any one of the preceding claims.
A compound for use as a diagnostic or therapeutic agent in a subject, said compound comprising a diagnostic or therapeutic agent operably linked to a CD98hc binding moiety of any one of claims of the preceding claims, wherein said binding moiety is endocytosed to thereby deliver said diagnostic or therapeutic agent across the cell membrane.
A method of delivering a therapeutic or diagnostic molecule across the blood brain barrier which comprises administering a CD98hc binding moiety of the preceding claims, wherein said therapeutic molecule is conjugated to said moiety, to a subject for a time and in an amount effective to treat or diagnose a CNS disease or condition.
A method of delivering a therapeutic or diagnostic molecule to one or more tissues, cells or organs selected from the group consisting of a tumor, a lymphocyte, a lymph node, a parathyroid gland, a kidney, a pancreatic s tissue, an esophageal tissue and a placenta which comprises administering a CD98hc binding moiety of any one of the preceding claims, wherein said therapeutic molecule is conjugated to said moiety, to a subject for a time and in an amount effective to treat or diagnose a disease or condition associated with said tissue, cell or organ.
A method of increasing the oral bioavailability of a drug which comprises associating the drug with a CD98hc-binding moiety of any one of the preceding claims.
A composition comprising a plurality of 50 or more semi-synthetic polypeptides comprising Type IV VNAR framework (FW), hypervariable (HV) and complementary determining region (CDR) regions having a domain structure, from N- to C-terminus of
Dependencies are inferred from the claim text.