Abstract: The present invention relates to a modified ?-Glucocerebrosidase (GCase) polypeptide and a polynucleotide comprising a modified glucocerebrosidase (GBA) nucleotide sequence. The invention further relates to a viral particle comprising a recombinant genome comprising the polynucleotide of the invention, and a composition comprising the modified GCase polypeptide, polynucleotide, or viral particle of the invention. The invention also relates to methods of using, and uses of, the modified GCase polypeptide, polynucleotide, viral particle and/or composition of the invention. The invention further relates to the modified GCase polypeptide, polynucleotide, viral particle, or composition of the invention for use in a method of treatment, or use in the manufacture of a medicament for use in a method of treatment.

Abstract: 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.

Abstract: 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.

Abstract: The present invention provides Factor VIII polypeptides which comprise one or more substitution mutations compared to a corresponding wild-type Factor VIII, wherein the one or more substitution mutations are located at an inter-domain interface between two domains of the Factor VIII polypeptide. Also provided are polynucleotides comprising a Factor VIII nucleotide sequence encoding a Factor VIII polypeptide of the invention, recombinant AAV constructs comprising such polynucleotides, AAV viral particles comprising such recombinant AAV constructs, compositions comprising the Factor VIII polypeptide, polynucleotide, recombinant AAV construct, or AAV viral particle of the invention, and the use of the Factor VIII polypeptides, polynucleotides, recombinant AAV constructs, AAV viral particles and compositions of the invention in therapy.

Abstract: The present invention relates to a Factor VIII (FVIII) polypeptide, a polynucleotide comprising a Factor VIII nucleotide sequence, and a recombinant AAV construct. The invention further relates to an AAV viral particle comprising the recombinant AAV construct of the invention, and a composition comprising the Factor VIII polypeptide, polynucleotide, recombinant AAV construct or AAV viral particle of the invention. The invention also relates to methods of using, and uses of, the Factor VIII polypeptide, polynucleotide, recombinant AAV construct, AAV viral particle and/or composition of the invention. The invention also relates to uses of the recombinant AAV construct of the invention for the production of AAV viral particles, and methods for producing AAV viral particles using the recombinant AAV constructs of the invention.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention describes novel hetero-dimeric immunoglobulinvariants or fragments thereof, which have reduced or eliminated binding to Protein A, Protein G or both Protein A and Protein G. Also encompassed in the present invention are methods for the selective purification of hetero-dimeric immunoglobulins or fragments thereof using Protein A and Protein G.

Abstract: 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.

Abstract: The present invention describes novel hetero-dimeric immunoglobulinvariants or fragments thereof, which have reduced or eliminated binding to Protein A, Protein G or both Protein A and Protein G. Also encompassed in the present invention are methods for the selective purification of hetero-dimeric immunoglobulins or fragments thereof using Protein A and Protein G.

Abstract: The invention discloses high levels of receptors for Clostridium perfringens enterotoxin (CPE) have been found in ovarian cancer and uterine cancer tissue samples. In addition, successful in vivo treatment of a mouse model of ovarian cancer with intraperitoneal injection of CPE is disclosed. High levels of Ep-CAM protein is also disclosed in ovarian cancer tissue samples. Thus, the invention provides a method of treating ovarian cancer and uterine cancer by administering CPE. The invention also provides a method of treating cancer in a mammal involving intraperitoneal administration of CPE, where at least some cancerous cells are located in or adjacent to the peritoneal cavity of the mammal. The invention also provides a method of treating ovarian cancer involving administering an anti-Ep-CAM antibody. The invention also provides a method of treating cancers expressing claudin-3 or claudin-4 by administering an antibody against claudin-3 and/or an antibody against claudin-4.

Abstract: The invention discloses high levels of receptors for Clostridium perfringens enterotoxin (CPE) have been found in ovarian cancer and uterine cancer tissue samples. In addition, successful in vivo treatment of a mouse model of ovarian cancer with intraperitoneal injection of CPE is disclosed. High levels of Ep-CAM protein is also disclosed in ovarian cancer tissue samples. Thus, the invention provides a method of treating ovarian cancer and uterine cancer by administering CPE. The invention also provides a method of treating cancer in a mammal involving intraperitoneal administration of CPE, where at least some cancerous cells are located in or adjacent to the peritoneal cavity of the mammal. The invention also provides a method of treating ovarian cancer involving administering an anti-Ep-CAM antibody. The invention also provides a method of treating cancers expressing claudin-3 or claudin-4 by administering an antibody against claudin-3 and/or an antibody against claudin-4.