Ossianix, Inc.

Pawel Stocki

Julia Lynn Rutkowski

Krzysztof Bartlomiej Wicher

Jaroslaw Michal Szary

Fabrizio Comper

Mykhaylo Demydchuk

Cyril V Privezentzev

Aziz Gauhar

Laura Thei

Shu-Fen Coker

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to improved TfR-binding moieties capable of crossing the blood brain barrier (BBB) and capable of carrying and releasing cargo specifically targeted to the parenchymal tissue of the brain. The present invention relates to a transcytosis selection method to obtain VNARs against mammalian blood brain barrier (BBB) receptors using phage display libraries as well as against receptors found in other directional cell barrier systems like the gastrointestinal tract and other organs. The VNARs may be used alone or as components in compositions or as conjugates that target the particular receptor transport systems for delivery of therapeutics or diagnostics to the brain (in the case of BBB receptors) or other tissues.

TFR-specific binding moieties and transcytosis method to select VNARs that cross cellular barriers

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to improved TfR-binding moieties based on shark VNARs capable of crossing the blood brain barrier (BBB) and capable of carrying and releasing cargo specifically targeted to the parenchymal tissue of the brain.

Transferrin receptor (TFR)-selective binding peptides capable of crossing the blood brain barrier, encoding nucleic acids thereof and methods of use thereof

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.

Anti-CD98hc VNARs for crossing the blood brain barrier and type IV VNAR libraries

The present invention relates to a high affinity, VNAR polypeptide cross reactive with primate transferrin receptors ('TfR'). This TfR-specific VNAR polypeptide was obtained by screening semisynthetic VNAR phage display libraries against recombinant human TfR-1. The VNAR polypeptides of the invention can be used alone or as a component in conjugates that target the transferrin/transferrin receptor transport system. The invention further includes use of this VNAR, its conjugates and other derivatives in diagnostic and therapeutic methods, 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 or other membrane systems. This TfR-specific VNAR polypeptide can also be used to target other biological barriers such the intestines, the placenta or aberrant cells overexpressing TfR-1, for therapeutic benefit in treatment of certain cancer cells and tumors of various tissue types. Deimmunized VNAR scaffolds are also provided.

Type-II VNAR polypeptides which bind human TfR-1, encoding nucleic acids thereof and method of use thereof

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to the methods used to identify membrane receptors or transporters capable of carrying cargo specifically targeted to the parenchymal tissue of the brain and to in vivo enrichment methods for selecting peptides that are transported across the blood-brain barrier ('BBB'), or analogously, across other membrane containing organs or structures, such as liver, spleen, kidney and tumors.

In vivo methods for selecting peptides that cross the blood brain barrier, related compositions and methods of use

Transferrin receptor (TfR)-selective binding peptides capable of crossing the blood brain barrier and methods of use thereof

The present disclosure provides coronavirus S1-fragment specific binding moieties comprising Type II VNAR domains, VNAR antibodies, methods of using those moieties and antibodies to treat COVID-19. In some embodiments, a VNAR antibody, originally selected from a phage display library as a VNAR clone using S1fragments from the SARS-CoV-2 Wuhan strain, are also effective at specifically binding to and/or neutralizing SARS-CoV-2 and certain SARS-CoV-2 mutants.

Growing community of inventors

Royston, United Kingdom

Pawel Stocki