The present disclosure relates to methods for treating type 1 diabetes (T1D) using a glucagon receptor blocking agent. More specifically, the present disclosure relates to methods for treating T1D using substantially lower doses of insulin supplementation, or even in the absence of insulin supplementation, using antigen binding and antagonizing proteins, e.g., fully human antibodies that specifically bind to and antagonize the function of the human glucagon receptor.

The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.

The present invention relates to mixtures comprising: i) at least one lipid and/or at least one oil; and ii) an alkyl ammonium EDTA salt; wherein the mixture has a water content in the range of 0 to 1.0 wt %.

The invention further relates to mixtures which are pre-formulations, methods of treatment comprising administration of such pre-formulations, to pre-filled administration devices and kits containing the formulations, to the use of an alkylammonium EDTA salt to reduce the decomposition of the lipid components and/or any active agent contained within the pre-formulation, and to alkyl ammonium EDTA salts as described herein.

The invention provides 5-deuterium-enriched 2,4-thiazolidinediones (e.g., 5-[4-[2-(5-ethyl-2-pyridyl)-2-oxoethoxy]benzyl]-5-deutero-thiazolidine-2,4-dione), deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same.

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

The present invention relates to methods of enhancing the potency of incretin-based drugs in subjects in need thereof. Through different animal models, the inventors identified that a specific gut microbiota signature impairs GLP-1-activated gut-brain axis which could be transferred to germ free mice. The dysbiotic gut microbiota induces enteric neuropathy, reduces GLP-1 receptor and nNOS mRNA concentration, GLP-1-induced nitric oxide production for the control of insulin secretion and gastric emptying. The frequency of Lactobacilli in the ileum microbiota was tightly correlated with nMOS mRNA concentration, which is a mode of action of GLP-1, of the enteric nervous system opening a novel route for the improvement of GLP-1 based therapies in type 2 diabetic patients. In particular, the present invention relates to a method of enhancing the potency of an incretin-based drug administered to a diabetic subject as part of a treatment regimen.

The present invention relates to methods of enhancing the potency of incretin-based drugs in subjects in need thereof. Through different animal models, the inventors identified that a specific gut microbiota signature impairs GLP-1-activated gut-brain axis which could be transferred to germ free mice. The dysbiotic gut microbiota induces enteric neuropathy, reduces GLP-1 receptor and nNOS mRNA concentration, GLP-1-induced nitric oxide production for the control of insulin secretion and gastric emptying. The frequency of Lactobacilli in the ileum microbiota was tightly correlated with nMOS mRNA concentration, which is a mode of action of GLP-1, of the enteric nervous system opening a novel route for the improvement of GLP-1 based therapies in type 2 diabetic patients. In particular, the present invention relates to a method of enhancing the potency of an incretin-based drug administered to a diabetic subject as part of a treatment regimen.

The present invention relates to amylin analogues and to their use in the treatment or prevention of a variety of diseases, conditions or disorders, including obesity, excess food intake and associated metabolic diseases such as diabetes. The analogues have good physical and chemical stability, good solubility, and a long duration of action, and are well suited for use in the form of a liquid formulation.

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex prepared by the present invention may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.