The invention provides peptides and analogs of INGAP and HIP peptides. The peptides and analogs can be used in methods for treating various diseases and conditions. Such diseases and conditions can include impaired pancreatic function, treating a metabolic disease, for example, diabetes, both type 1 and type 2 diabetes, islets induction, expansion and proliferation for trans plantation, promoting neuroprotection or nerve regeneration, promoting liver regeneration or inhibiting inflammation.

The invention provides peptides and analogs of INGAP and HIP peptides. The peptides and analogs can be used in methods for treating various diseases and conditions. Such diseases and conditions can include impaired pancreatic function, treating a metabolic disease, for example, diabetes, both type 1 and type 2 diabetes, islets induction, expansion and proliferation for trans plantation, promoting neuroprotection or nerve regeneration, promoting liver regeneration or inhibiting inflammation.

Methods, compositions and kits useful in the detection, assessment, diagnosis, prognosis and/or treatment of brain injuries, especially mild traumatic brain injury (mTBI) or concussion, are based upon detection of changes in levels of certain protein biomarkers in a subject undergoing testing, or upon detection of changes in levels of certain protein biomarkers in conjunction with neuroimaging analyses to detect changes in vascular or blood brain barrier (BBB) permeability in the brain, or to detect damage to fiber tracts in the brain, in which changes in biomarker levels correlate with detection of changes in BBB permeability or in brain fiber tract or white matter damage in a subject with brain injury such as mTBI or concussion.

A fusion protein including a GDF15 variant having increased physiological activity and in vivo stability, and a pharmaceutical composition containing the same are disclosed. The GDF15 variant or long-acting GDF15 fusion protein is superior to conventional GDF15 variants in terms of in vitro efficacy, binding affinity for GDF15 receptors, and body weight loss effect. Therefore, a pharmaceutical composition containing, as an active ingredient, the GDF15 variant, the long-acting GDF15 fusion protein, or a dimer of the fusion protein, causes appetite suppression, and thus can be effectively used as a therapeutic agent for metabolic diseases or obesity. Furthermore, the pharmaceutical composition can be used in combination therapy or the like with chemical drugs and other therapeutic agents for metabolic diseases, and can be effectively used in combination therapy with conventional therapeutic agents for metabolic diseases or obesity.

A fusion protein including a GDF15 variant having increased physiological activity and in vivo stability, and a pharmaceutical composition containing the same are disclosed. The GDF15 variant or long-acting GDF15 fusion protein is superior to conventional GDF15 variants in terms of in vitro efficacy, binding affinity for GDF15 receptors, and body weight loss effect. Therefore, a pharmaceutical composition containing, as an active ingredient, the GDF15 variant, the long-acting GDF15 fusion protein, or a dimer of the fusion protein, causes appetite suppression, and thus can be effectively used as a therapeutic agent for metabolic diseases or obesity. Furthermore, the pharmaceutical composition can be used in combination therapy or the like with chemical drugs and other therapeutic agents for metabolic diseases, and can be effectively used in combination therapy with conventional therapeutic agents for metabolic diseases or obesity.

The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.

The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present disclosure provides binding agents, such as antibodies, that specifically bind Angiopoietin-like protein 8 (ANGPTL8), including human ANGPTL8, and methods of their use.