Described herein are compositions of pyrvinium salts suitable for oral administration. These compositions are in the form of solutions and demonstrate bioavailability both in blood plasma and in pancreatic tissue. Also described herein are methods of treating, ameliorating, and/or preventing pancreatic cancer, including orally administering a composition comprising pyrvinium pamoate.

Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Disclosed herein are methods and compositions for the cryopreservation of stem cells, such as stem-cell derived retinal pigment epithelial cells, that have been seeded onto and cultured on a substrate, such as a polymeric substrate. Such cryopreserved stem cells are useful for cell therapies, such as treatment of ocular damage or disease.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Provided are novel compounds of Formula (I): ##STR00001##
pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I) and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

The disclosure relates to stem cells and their therapeutic use in the treatment and/or prevention of pancreatic diseases or disorders. Provided herein are compositions comprising c-kit positive pancreatic stem cells and methods of preparing and using c-kit positive pancreatic stem cells for the treatment and/or prevention of pancreatic diseases or disorders.

This invention discloses certain methods of treating acute pancreatitis and inflammatory pancreatic disease or condition. The disclosed peptides and analogs can significantly lower the elevated blood amylase and lipase levels caused by acute pancreatitis and pancreatic inflammation, reduce the degree of injury observed in pancreatic histopathology caused by pancreatitis, and significantly lower the mortality rate of acute pancreatitis.

This invention discloses certain methods of treating acute pancreatitis and inflammatory pancreatic disease or condition. The disclosed peptides and analogs can significantly lower the elevated blood amylase and lipase levels caused by acute pancreatitis and pancreatic inflammation, reduce the degree of injury observed in pancreatic histopathology caused by pancreatitis, and significantly lower the mortality rate of acute pancreatitis.

The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the complement lectin/mannose pathway (CMP), or combinations thereof, as well as methods and materials for targeting diagnostic, prophylactic and therapeutic agents to localized areas of tissue within the body where they may more directly exert their effects upon the intended target cells or tissue, with reduced, associated systemic effects compared with administration of the same or similar agents in an untargeted, systemic manner. The methods and materials of the present invention may therefore allow for increased efficacy, lower threshold effective dosages and/or lower effective maintenance doses, and/or reduced associated undesired or adverse effects in terms of frequency or severity of occurrence, or both. The present invention also relates to methods and materials for modulating a host humoral immune response, especially reducing, inhibiting, or preventing a host humoral immune response.

The present invention provides monovalent antibodies with a long half-life when administered in vivo, methods of making such monovalent antibodies, pharmaceutical compositions comprising such antibodies, and uses of the monovalent antibodies.