Abstract: Stable injectable compositions comprising glucagon or a pharmaceutically acceptable salt, solvate, or hydrate thereof are disclosed, which comprise (a) a therapeutically effective amount of glucagon; (b) at least one pharmaceutically acceptable solvent; (c) at least one stabilizing agent; (d) at least one sugar; and (e) optionally, at least one pharmaceutically acceptable excipient; wherein said injectable solution is stable and ready-to-use, and wherein pH of the said solution ranges from 3.8 to 4.2. Preferably, the composition is provided in a sealed container, e.g., an ampoule, a vial, a pre-filled syringe or an auto-injector. Further, stable injectable solutions are disclosed, which comprise glucagon or a pharmaceutically acceptable salt, solvate, or hydrate thereof, and which are suitable for subcutaneous, intravenous or intramuscular administration. Methods for manufacturing stable injectable solutions of glucagon are also disclosed.

Abstract: The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, antibodies, antibody fragments, etc., that specifically bind a TREM2 protein, e.g., a mammalian TREM2 or human TREM2, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

Abstract: Provided herein are protein-based purification matrices and methods of use thereof to purify biologics and/or to remove contaminants from a composition. Methods of bringing two or more biologics in close proximity are also provided. The disclosed compositions and methods allow for faster, more efficient purification of a biologic compared to traditional affinity chromatography.

Abstract: The invention relates to a derivative of a GLP-1 peptide, which peptide comprises a first K residue and a second K residue, at positions corresponding to position 26, and 34, respectively, of GLP-1(7-37) (SEQ ID NO:1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is Chem. 2: HOOC—C6H4—O—(CH2)y—CO—*, in which y is an integer in the range of 6-13; and the linker comprises Chem. 3a: *—NH—(CH2)q—CH[(CH2)w—NR1R2]—CO—*, wherein q is an integer in the range of 0-5, R1 and R2 independently represent *—H or *—CH3, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptide and linker intermediates.

Abstract: The present invention relates to an isolated transgenic pig beta cell wherein the PKC and the PKA pathway are constitutively activated; to a transgenic pig islet comprising said transgenic pig beta cell; and to a transgenic pig comprising said transgenic pig beta cell or said transgenic pig islet. Another object of the invention is a device comprising a transgenic pig beta cell or a transgenic pig islet of the invention. The present invention also relates to the use of said transgenic pig beta cell, said transgenic pig islet, or said device for treating a disease, disorder or condition related to the impaired function of endocrine pancreas or of beta cell.

Abstract: The invention relates to compounds having agonist activity at the GLP-1 (glucagon-like-peptide 1) and GLP-2 (glucagon-like peptide 2) receptors. The compounds find use, inter alia, in the prophylaxis or treatment of intestinal damage and dysfunction, regulation of body weight, and prophylaxis or treatment of metabolic dysfunction.

Abstract: The invention relates to pharmaceutical compositions comprising a first type of granules and a second type of granules, wherein said first type of granules comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and no GLP-1 peptide, and wherein said second type of granules comprises a GLP-1 peptide and no salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, as well as the intermediate granules, processes for the preparation of the granules and compositions, and use thereof in medicine.

Abstract: This invention relates to ready-to-use and safe solution compositions of glucagon suitable for administration by manual injection or by an insulin pump or other injection device to treat hypoglycemia. Said compositions comprise glucagon, an acid, anti-gelling polyol, a stabilizing-salt, viscosity reducer and an antioxidant, have a final pH between about 2 and 5, and is gel-free, chemically-stable, and pump-able.

Abstract: Provided is an incretin, or analogue thereof, an incretin receptor agonist, an incretin enhancer, or any combination thereof, for use in a method of reducing elevated intracranial pressure (ICP) in a subject. Methods of reducing elevated ICP in a subject may comprise administering an incretin, or analogue thereof, an incretin receptor agonist, an incretin enhancer, or any combination thereof to the subject. The elevated ICP may be associated with idiopathic intracranial hypertension (IIH), secondary pseudotumour cerebri, hydrocephalus, normal pressure hydrocephalus, raised intracranial pressure secondary to a brain tumour, meningitis, brain trauma, brain injury, and venous sinus thrombosis.

Abstract: The invention relates to a derivative of a GLP-1 peptide, which peptide comprises a first Lys residue at a position corresponding to position 36 of GLP-1(7-37) (SEQ ID NO: 1), a second Lys residue at a position corresponding to position 37 of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of seven amino acid changes as compared to GLP-1(7-37) (SEQ ID NO: 1); which derivative comprises two protractors attached to said first and second Lys residue, respectively, each via a linker; wherein the protractor is selected from: HOOC—C6H4—O—(CH2)y—CO—*, and??Chem. 1: HOOC—(CH2)x—CO—*,??Chem. 2: wherein y is an integer in the range of 8-11, and x is 12; and the linker comprises at least one of: *—NH—CH(COOH)—(CH2)2—CO—*,??Chem. 3: *—NH—CH((CH2)2—COOH)—CO—*, and/or??Chem. 4: *—NH—(CH2)2—[O—(CH2)2]k—O—[CH2]n—CO—*,??Chem. 5: wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof.

Abstract: The present invention relates to a fusion polypeptide containing a glucagon-like peptide (GLP) and an immunoglobulin hybrid Fc, and more specifically, to a fusion polypeptide with an increased half-life and improved efficacy compared to the conventional fusion polypeptide based on the discovery of an immunoglobulin hybrid Fc suitable for GLP or analogs thereof, and a pharmaceutical composition for treating diabetes, inflammatory bowel disease, endoenteritis or diarrhea caused by anticancer chemotherapy, or short bowel syndrome, containing the fusion polypeptide. The fusion polypeptide of the present invention has an increased half-life and improved resistance to DPP-4 enzyme compared to those of GLP-1 and GLP-2, and it thus has improved drug efficacy in treating diabetes, inflammatory bowel disease, endoenteritis or diarrhea caused by anticancer chemotherapy, or short bowel syndrome, compared to those of the conventional drugs.

Abstract: This document provides methods and materials related to insulin secreting polypeptides. For example, polypeptides having the ability to induce insulin secretion and methods and materials for using use such polypeptides to induce insulin secretion and to treat diabetes are provided.

Abstract: The invention is directed to a method for producing a polypeptide composition comprising: combining a polypeptide with a volatile additive to form a liquid mixture and lyophilizing the liquid mixture to obtain a lyophilized polypeptide composition.

Abstract: The present invention relates to an albumin-free liquid formulation comprising a long-lasting oxyntomodulin conjugate in which an oxyntomodulin peptide comprising a derivative, variant, precursor or fragment of oxyntomodulin is linked to an immunoglobulin Fc region, which can increase the duration of physiological activity of the long-lasting oxyntomodulin conjugate and maintain the in vivo stability thereof for an extended period of time, as compared to native oxyntomodulin, as well as a method for preparing the liquid formulation. The liquid formulation comprises a buffer, a sugar alcohol and a nonionic surfactant and does not contain a human serum albumin and factors that are potentially harmful to the human body, and thus is not susceptible to viral infection.

Abstract: This invention relates to compositions of glucagon suitable for administration by manual injection or by an insulin pump or other injection device to treat hypoglycemia. Said compositions comprise glucagon and a sugar, have a final pH between about 1.5 and 3, and are gel-free, chemically-stable at body temperature and pump-able.

Abstract: The use of GLP-1 receptor agonists, such as glucagon-like peptide-1 (GLP-1) or exenatide, for the treatment of cancer is described. The GLP-1 receptor agonists are typically delivered using an implanted osmotic delivery device that provides for continuous delivery of the GLP-1 receptor agonist for at least one month. Additional beneficial agents, such as anticancer agents, can also be administered.

Abstract: Methods of treating obesity, metabolic syndrome, hepatic and non-hepatic steatosis, and diabetes using a pentapeptide, LVKGRamide, derived from the C-terminus of Glucagon-Like Peptide 1 (GLP-1).

Abstract: C-Terminal Fragments of Glucagon-Like Peptide-1 (GLP 1), and methods of use thereof, e.g., for the treatment of obesity and obesity-related disorders, e.g., diabetes and the metabolic syndrome.

Abstract: The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4—O—(CH2)y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NR1R2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R1 and R2 independently represent *—H or *—CH3, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof.

Abstract: This document provides methods and materials related to insulin secreting polypeptides. For example, polypeptides having the ability to induce insulin secretion and methods and materials for using use such polypeptides to induce insulin secretion and to treat diabetes are provided.

Abstract: There is disclosed a composition and a method for the efficient delivery of a therapeutic RNAi-inducing nucleic acid to cells both in vitro and in vivo through specific formulations of a non viral delivery system using chitosans. Particularly, the composition contains a nucleic acid and a specific chitosan that has the following physico-chemical properties: a number-average molecular weight between 5 kDa and 200 kDa, a degree of deacetylation between 80% and 95% and a chitosan amine to nucleic acid phosphate ratio below 20.

Abstract: There is provided glucagon formulations suitable for preparing coatings on microneedle patches for the transdermal delivery of glucagon. The coated patches may be used for the treatment of low blood sugar in diabetic patients. Also provided are glucagon loaded patches, methods for their preparation, and methods of their use.

Abstract: Disclosed are an albumin-free liquid formulation including a long-lasting oxyntomodulin conjugate in which an oxyntomodulin peptide comprising a derivative, variant, precursor or fragment of oxyntomodulin is linked to an immunoglobulin Fc region, which can increase the duration of physiological activity of the long-lasting oxyntomodulin conjugate and maintain the in vivo stability thereof for an extended period of time, as compared to native oxyntomodulin, and a method for preparing the liquid formulation. The liquid formulation contains a buffer, a sugar alcohol and a nonionic surfactant and does not contain a human serum albumin and factors that are potentially harmful to the human body, and thus is not susceptible to viral infection. The oxyntomodulin conjugate contains oxyntomodulin linked to an immunoglobulin Fc region, and thus has a large molecular weight, prolonged physiological activity, and excellent storage stability, compared to native oxyntomodulin.

Abstract: A peptide compound useful in the treatment of hypoglycemia is described.

Abstract: A peptide compound useful in the treatment of hypoglycemia is described.

Abstract: The invention relates to truncated GLP-1 analogs, in particular a GLP-1 analog which is a modified GLP-1(7-35) (SEQ ID No 1) having: i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a Glu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogs and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.

Abstract: A formulation composed of a sugar such as glucose and a surfactant such as myristoyl lysophosphocholine (LMPC) has been designed to stabilize both hydrophilic and hydrophobic portions of the glucagon molecule, under prolonged physiological conditions, in a formulation that is sufficiently similar to the pH and osmolarity of plasma so as not to induce or to minimize site irritation. The combination of a simple sugar and an surfactant stabilizes the glucagon molecule in an aqueous solution for seven days at 37° C.

Abstract: Peptide analogs of glucagon and peptide analogs of GLP1 are provided herein. Also provided herein are pharmaceutical compositions comprising the analogs, and methods of using the analogs for the treatment and/or prevention of conditions such as obesity and diabetes.

Abstract: The invention relates to derivatives of GLP-1 like peptides which are C-terminally extended analogs of native GLP-1. The derivatives comprise two side chains, one at a position corresponding to position 42, and one at a position corresponding to position 18, 23, 27, 31, 36, or 38, wherein both positions are when compared to GLP-1(7-37). The side chains comprise a C19, C20, or C22 diacid protracting moiety and optionally a linker. The invention also relates to intermediate products in the form of novel GLP-1 analogs incorporated in the derivatives of the invention, as well as pharmaceutical compositions and medical uses of the derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.

Abstract: There is provided glucagon formulations suitable for preparing coatings on microneedle patches for the transdermal delivery of glucagon. The coated patches may be used for the treatment of low blood sugar in diabetic patients. Also provided are glucagon loaded patches, methods for their preparation, and methods of their use.

Abstract: The invention provides a method of treating a subject having, or at risk of developing, a condition in which functioning of the small or large intestine is impaired, enhancing functioning or preventing damage to the small or large intestine in a subject, or ameliorating inflammation of the small or large intestine in a subject, comprising administering to the subject a GLP-1 receptor agonist. A GLP-1 receptor agonist may also be provided in a pharmaceutically acceptable form in an amount effective to treat or prevent conditions of the small or large intestine. Further, pharmaceutical compositions are provided for the treatment or prevention of conditions of the small or large intestine comprising a GLP-1 receptor agonist, together with a pharmaceutically acceptable carrier, excipient or vehicle.

Abstract: Disclosed is a novel long-acting glucagon conjugate in which glucagon or its derivative is covalently linked to a polymer carrier via a non-peptide linker, and a pharmaceutical composition comprising the same as an effective ingredient useful for the prevention and treatment of obesity. Since the long-acting glucagon conjugate of the present invention shows improved in vivo durability and stability, when used in combination with an anti-obesity drug, it is possible to induce synergistic effects on the loss of body weight and decrease in food intake without causing any side-effects such as fluctuation in blood glucose level. Accordingly, the long-acting peptide conjugate of the present invention is very effective for the prevention and treatment of obesity.

Abstract: Intestinal absorption is enhanced in short bowel syndrome patients presenting with colon-in-continuity by treatment with a GLP-2 receptor agonist, such as teduglutide.

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: A composition which includes oxyntomodulin and polyethylene glycol polymer (PEG polymer) linked via a reversible linker such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) is disclosed. Pharmaceutical compositions comprising the reverse pegylated oxyntomodulin and methods of using same are also disclosed.

Abstract: Methods for treating fatty liver disease, e.g., hepatic steatosis, using peptide fragments of the C-terminal end of glucagon-like peptide-1 (GLP-1), e.g., GLP-1(28-36).

Abstract: The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4—O—(CH2)y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NR1R2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R1 and R2 independently represent *—H or *—CH3, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof.

Abstract: C-Terminal Fragments of Glucagon-Like Peptide-1 (GLP 1), and methods of use thereof, e.g., for the treatment of obesity and obesity-related disorders, e.g., diabetes and the metabolic syndrome.

Abstract: GLP-2 analogues are disclosed which comprise one of more substitutions as compared to h[Gly2]GLP-2 and which may have the property of an altered GLP-1 activity, and their medical use. The analogues are particularly useful for the prophylaxis, treatment or ameliorating of the gastro-intestinal associated side effects of diabetes.

Abstract: There is provided according to the invention an aqueous composition having pH between 4 and 7 comprising (i) glucagon at a concentration of 0.05% w/v or more and (ii) a cationic surfactant selected from benzalkonium salts and benzethonium salts as solubilizing agent in an amount sufficient to dissolve the glucagon in the composition.

Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel acylated glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: The invention relates to a derivative of a GLP-1 analog, which analog comprises a first K residue at a position corresponding to position 18 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4-0-(CH2)y—CO—*, in which x is an integer in the range of 6-18, and y is an integer in the range of 3-17; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NH2]—CO—*, wherein q is an integer in the range of 0-5, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof.

Abstract: The present invention relates to a soluble hydrophobic-core carrier composition comprising (i) a linear polymeric backbone; (ii) a plurality of hydrophilic polymeric protective chains covalently linked and pendant to the polymeric backbone and (iii) at least one hydrophobic moiety covalently linked and pendant to the polymeric backbone. In certain embodiments, the weight ratio of hydrophilic protective chains to hydrophobic moieties in the carrier is at least 15:1. In other embodiments, at least 90% of the residues of the polymeric backbone are coupled to a hydrophilic polymeric protective chain or a hydrophobic moiety. In other embodiments, the composition further comprises (iv) a hydrophobic load molecule dissociably linked to the hydrophobic moiety of the carrier.

Abstract: The invention generally relates to compositions and methods for the reduction or neutralization of toxins associated with a bacterial, mycobacterial, fungal, viral, or protozoal agent. More particularly, the invention is directed to sterically stabilized phospholipid micellar and liposomal compositions, which interact with the toxins to decrease or neutralize their toxicity. Additionally, the invention includes the use of sterically stabilized phospholipid micellar compositions comprising one or more water-insoluble antibiotic, antifungal, antiviral, antiprotozoal, or anti-inflammatory agent(s), wherein the micellar or liposomal composition inhibits the formation of aggregates. The invention further includes the use of sterically stabilized micelle and liposomal compositions to deliver compounds to the site of action, and in some cases targets the compound to the site of action, for the treatment of inflammation and infection.

Abstract: Methods for reducing gastric motility and delaying gastric emptying for therapeutic and diagnostic purposes are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist. Methods for treating conditions associated with elevated, inappropriate, or undesired post-prandial blood glucose levels are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist alone or in conjunction with other anti-gastric emptying agents.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metabolic syndrome and associated disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: Provided herein are formulations containing exendins, exendin agonists and/or exendin analogs and methods of using the exendins, exendin agonists and/or exendin analogs and formulations thereof to treat glucagonoma and necrolytic migratory erythema, or to suppress glucagon secretion.

Abstract: The invention relates to pharmaceutical compositions comprising a first type of granules and a second type of granules, wherein said first type of granules comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and no GLP-1 peptide, and wherein said second type of granules comprises a GLP-1 peptide and no salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, as well as the intermediate granules, processes for the preparation of the granules and compositions, and use thereof in medicine.

Abstract: The invention relates to novel polypeptide analogs of GLP-1 and exendin-4. The polypeptide, in a preferred embodiment, is insulinotropic and long-acting. Preferably, the polypeptide's insulinotropic effect is comparable to or exceeds the effect of an equimolar amount of GLP-1 or exendin-4. The invention also relates to a method of treating a subject with diabetes, comprising administering to the subject the polypeptide of the invention in an amount that has an insulinotropic effect. The invention also relates to methods of using GLP-1, exendin-4, and polypeptide analogs thereof for neuroprotective and neurotrophic effects.