Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Abstract: The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind on or more epitopes within a Sortilin protein, e.g., human Sortilin or a mammalian Sortilin, and use of such compostions in preventing, reducing risk, or treating an individual in need thereof.

Abstract: Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Abstract: The inventors have produced two high specificity and high affinity monoclonal antibodies that bind to human neuromedin U (NMU). Methods and compositions are provided for treating an individual in need thereof (e.g., an individual who is obese and/or has diabetes) by administering an anti-NMU/NMUR agent (e.g., an anti-NMU antibody). For example, methods and compositions are provided for increasing circulating insulin in an individual. Methods and compositions are also provided for detecting neuromedin U (NMU) (e.g., in a biological sample such as serum). Methods and compositions are also provided for predicting whether an individual will develop diabetes and/or PDAC, and for identifying an individual who would benefit from administration of an anti-NMU/NMUR agent.

Abstract: Methods of treating metabolic diseases and disorders using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the antigen binding protein is administered in combination with a GLP-1 receptor agonist.

Abstract: Methods are disclosed for mitigating radiation injury to a subject by administration of ghrelin.

Abstract: The present invention is in the field of pharmaceutical compositions for the treatment of medical conditions relating to diabetes. More specifically the invention provides pharmaceutical compositions comprising a long-acting acylated derivative of a human insulin analog, and to the medical use of such compositions for basal insulin administration therapy.

Abstract: Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade within the wall to release the drug to produce a therapeutic effect. The preparation can be coupled to an actuator having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

Abstract: The present invention relates to an insulin analog that has reduced insulin receptor binding affinity for the purpose of increasing the blood half-life of insulin, and long-acting insulin, a conjugate, and a method of preparing long-acting insulin using the same.

Abstract: The present invention provides a fusion protein comprising a therapeutic polypeptide fused to one or more flexible unstructured polypeptides and a trimeric scaffold protein. The flexible unstructured polypeptide sequence within the fusion protein is exhibited as one or more pCloud sequences derived from human fibrinogen alpha chain, and may be flanked by a proteinous connecting moiety of human origin. Also provided are pharmaceutical compositions comprising the fusion protein, nucleic acid molecules encoding the fusion protein, vectors containing the nucleic acids, host cells transformed with the vectors, and methods of making the fusion proteins of the invention, and use thereof.

Abstract: Embodiments of the invention provide shaped masses comprising one or more drugs such as proteins or polypeptides and methods for forming such shaped masses. One embodiment provides a shaped mass comprising a drug such as a protein or polypeptide having a biological activity in the body of a mammal. The shaped mass is formed by compression of a precursor material comprising the drug wherein an amount of biologically active drug in the mass is a preserved above a minimum level. Drugs which may be incorporated into the shaped mass may include one or more glucose regulating proteins such as insulin, incretins; and immunoglobulins such as TNF-inhibiting antibodies or interleukin neutralizing antibodies. Embodiments of the shaped mass may be incorporated into a tissue penetrating member which is inserted into the intestinal wall allowing for the oral delivery of proteins and peptides which would otherwise be degraded in the intestinal tract.

Abstract: A pharmaceutical compound for the treatment of obesity related disorder that is a conjugate of myristic acid and a leptin-related peptide. Preferably, the leptin-related peptide is OB3 that has been D-substituted at Leu-4. The resulting conjugate significantly improved the pharmacokinetic profile of the leptin-related peptide by extending its half-life from less than one hour to as long as twenty-eight hours, depending on the route of delivery, increasing uptake, reducing the rate of plasma clearance, and enabling the minimal effective dose to be reduced several fold.

Abstract: The present disclosure is directed to the treatment of diseases or conditions involving the buildup of fatty tissues, such as obesity, metabolic syndrome, type II diabetes, etc. A composition containing a monoclonal antibody directed against gastric inhibitory polypeptide is administered. This results in a reduced rate of weight gain and a marked decrease in lipid synthesis and accumulation.

Abstract: A first aspect of the invention relates to a single chain insulin analog comprising: (A) the A-chain of human or animal insulin, or an analog or derivative thereof; (B) the B-chain of human or animal insulin, or an analog or derivative thereof; (C) one or more disulfide bonds between said A-chain and said B-chain; and (D) a further covalent link, L, between a functional group of an amino acid in the A-chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.

Abstract: The present invention provides a method of intranasal delivery of a pharmaceutical composition, comprising a polysaccharide derivative of insulin protein and a one or more pharmaceutically acceptable excipients, to a subject, wherein the insulin protein is delivered to the brain of the subject through the nasal mucosa.

Abstract: A composition for preventing or treating diabetes mellitus includes insulin and a GLP-1/glucagon dual agonist. The composition can inhibit the weight gain and reduce the danger of hypoglycemia due to the administration of insulin, lower the administration dose and greatly improve the compliance of drugs through a combined administration of a long-acting insulin conjugate and a long-acting GLP-1/glucagon dual agonist conjugate. In addition, the long-acting insulin conjugate and the long-acting GLP-1/glucagon dual agonist conjugate can improve the in vivo sustainability and stability because an insulin and a GLP-1/glucagon dual agonist are linked to the immunoglobulin Fc region via a non-peptidyl linker. A method for preventing or treat diabetes mellitus includes administration of the insulin and a GLP-1/glucagon dual agonist.

Abstract: This invention relates to a method for detecting the presence of or likelihood of a patient of developing occult pancreatic beta cell dysfunction, and a method for detecting the presence of or likelihood of a patient of developing clinically significant post-prandial hyperglycemia. The methods involve (a) measuring a level of alpha-hydroxybutyrate (AHB) in a single fasting baseline biological sample of the patient; (b) comparing the level of AHB in the single fasting baseline biological sample to a reference AHB level; and (c) determining the presence of or likelihood of developing the disorder in the patient based on the comparison in step (b). An increased AHB level at fasting baseline indicates that a normoglycemic, normo-insulinemic and/or non-dyslipidemic patient has developed or has an increased likelihood of developing occult pancreatic beta cell dysfunction.