40 results about "GIP receptor" patented technology

The present invention provides fusion proteins comprising leptin and a second protein. The presence of the second protein provides increased biological activity and / or increased half-life in vivo. The present invention also provides human, canine and feline leptin molecules fused to peptides, antibodies or antibody fragments which enhances the abilities of the leptin molecules to transport through the blood-brain-barrier (BBB). The present invention also provides fusion proteins further comprising a peptide agonist that is capable of binding to and stimulate one, two or all three of the following receptors: GLP-1 receptor, Glucagon receptor, and GIP receptor. Also disclosed is a method of production such fusion proteins through recombinant technologies. The invention further discloses a pharmaceutical composition comprising one of the fusion proteins as an active intergradient as well as a method for using such a pharmaceutical composition to treat diseases in dogs, cats and humans.

Compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, methods of their therapeutic and / or prophylactic use, and methods of their use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor are provided. Certain compounds may have activity as modulators or potentiators with respect to glucagon receptor, GIP receptor, GLP-1 and GLP-2 receptors, and PTH receptor on their own or in the presence of receptor ligands such as GIP (1-42), PTH (1-34), Glucagon (1-29), GLP-2 (1-33), GLP-1 (7-36), GLP-1 (9-36), oxyntomodulin and exendin variants.

Glucagon peptides with increased GIP activity are provided, optionally with GLP-I and / or glucagon activity. In some embodiments, C-terminally extended glucagon peptides comprising an amino acid sequence substantially similar to native glucagon are provided herein.

The present invention relates to a long-acting conjugate of a triple agonist having activities to all of glucagon, GLP-1, and GIP receptors and uses thereof.

There is provided a novel series of analogues of glucose-dependent insulinotropic polypeptide compounds, pharmaceutical compositions containing said compounds, and the use of said compounds as GIP-receptor agonists or antagonists for treatment of GIP-receptor mediated conditions, such as non-insulin dependent diabetes mellitus and obesity.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and which play important roles in many cell types, including as described herein, the pancreatic β-cell. Glucagon like peptide-1 (GLP-1), a hormone released from intestinal L-cells following meal intake, exerts pleiotropic effects on β-cell function including raising intracellular cAMP levels and now represents an important therapy for type 2 diabetes. Expression of miR-132 and miR212 is upregulated by CREB protein in response increased cAMP levels in the cell; therefore, methods for detecting and evaluating β-cell engagement by GLP-1 receptor agonists by monitoring miR-132 and miR-212 expression in a subject is described. The methods herein are particularly useful in the context of longitudinal clinical trials, such as those designed for testing the durability of any single or combination therapy in type 2 diabetes populations. Because the expression of these miRNAs is not affected by glucose, fatty acid, insulin, or β-cell function, monitoring miR-132 and miR-212 expression can be used to monitor the efficacy of any agent that effects an increase cAMP in β-cells. Such agents include for example, GLP-1, glucagon, GPR-119, and GIP receptor agonists; dipeptidyl peptidase IV (DPP IV) inhibitors; and phosphodiesterase inhibitors.

Compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, methods of their therapeutic and / or prophylactic use, and methods of their use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor are provided. Certain compounds may have activity as modulators or potentiators with respect to glucagon receptor, GIP receptor, GLP-1 and GLP-2 receptors, and PTH receptor on their own or in the presence of receptor ligands such as GIP(1-42), PTH(1-34), Glucagon(1-29), GLP-2(1-33), GLP-1 (7-36), GLP-1 (9-36), oxyntomodulin and exendin variants.

Peptide analogues and uses are provided for treating and preventing obesity and for treating, preventing and reversing weight gain and related metabolic disease, and promoting weight loss and weight maintenance, by administering a medicament comprising an antagonist of GIP receptor, which is a peptide analogue of GIP.

A long-acting conjugate of a triple agonist which has activities to all of glucagon, GLP-1, and GIP receptors and uses thereof.

The present invention provides compounds which are analogs of glucose-dependent insulinotropic polypeptide (GIP) and pharmaceutically acceptable salts of such compounds. These compounds have activity as agonists of GIP receptor.

There is provided a novel series of analogues of glucose-dependent insulinotropic polypeptide compounds, pharmaceutical compositions containing said compounds, and the use of said compounds as GIP-receptor agonists or antagonists for treatment of GIP-receptor mediated conditions, such as non-insulin dependent diabetes mellitus and obesity.

The present invention relates to the field of biopharmaceuticals, and in particular to a protein, a protein conjugate, a pharmaceutical composition and its use for treating diabetes. The fusion protein of the present invention is obtained by linking two polypeptides, wherein one polypeptide is an interleukin-1 receptor antagonistic protein or an analogue thereof, and another polypeptide is GLP-1 receptor binding polypeptide or an analogue thereof, or an insulin receptor binding polypeptide or an analogue thereof, or a GIP receptor binding polypeptide or an analogue thereof. The fusion proteins of the present invention and conjugates thereof have a significant efficacy in treating diabetes, and can be used in a lower dose, resulting in marked reduction in side effects.

There is provided a novel series of analogues of glucose-dependent insulinotropic polypeptide compounds, pharmaceutical compositions containing said compounds, and the use of said compounds as GIP-receptor agonists or antagonists for treatment of GIP-receptor mediated conditions, such as non-insulin dependent diabetes mellitus and obesity.

The invention provides a GLP-1 / GCG receptor dual-agonist polypeptide compound. The GLP-1 / GCG receptor dual-agonist polypeptide compound provided by the invention can effectively reduce blood sugar, promote weight loss and prevent weight gain, reverse insulin resistance and regulate lipid metabolism. The polypeptide compound provided by the invention has higher agonistic activity on the GLP-1 receptor and the GCG receptor than natural ligands of each receptor, and has lower agonistic activity on a GIP receptor. The polypeptide compound provided by the invention is stable in chemical property, has low immunogenicity features, and is suitable for being used as an active ingredient of medicines for treating metabolic diseases such as diabetes, obesity, hyperlipidemia, NAFLD and NASH.

The present disclosure relates to heterodimeric fusion proteins comprising two polypeptides, the first polypeptide comprising a first peptide (P1), a linker (L1), and a Fc region (F1), the second polypeptide comprising a second peptide (P2), a linker (L2), and an Fc region (F2), wherein P1 and P2 are each independently selected from GLP-1, GLP-1 analogues, glucagon, glucacon analogues, GIP, GIP analogues, oxyntomodulin, oxyntomodulin analogues, exendin and exendin analogues; wherein F is selected from an IgG Fc, an IgA Fc, an IgE Fc, an IgGM Fc, and their analogues; wherein the C-terminals of the peptides are linked, though the Linker L, to the N-terminals of the Fc region F. In one embodiment, the fusion proteins disclosed herein have agonist activity against at least two of the GLP-1 receptor, the GIP receptor, and the glucagon receptor.

The present invention relates to a composition comprising insulin and a triple agonist having activity with respect to all of a glucagon receptor, GLP-1 receptor, and GIP receptor, and to a composite preparation comprising the composition.

The present invention relates to the field of biopharmaceuticals, and in particular to a protein, a protein conjugate, a pharmaceutical composition and its use for treating diabetes. The fusion protein of the present invention is obtained by linking two polypeptides, wherein one polypeptide is an interleukin-1 receptor antagonistic protein or an analogue thereof, and another polypeptide is GLP-1 receptor binding polypeptide or an analogue thereof, or an insulin receptor binding polypeptide or an analogue thereof, or a GIP receptor binding polypeptide or an analogue thereof. The fusion proteins of the present invention and conjugates thereof have a significant efficacy in treating diabetes, and can be used in a lower dose, resulting in marked reduction in side effects.

The present invention provides compounds which are analogs of glucose-dependent insulinotropic polypeptide (GIP) and pharmaceutically acceptable salts of such compounds. These compounds have activity as agonists of GIP receptor.

The present invention relates to a triple agonist having activities to all of glucagon, GLP-1, and GIP receptors and uses thereof.

There is provided a novel series of analogues of glucose-dependent insulinotropic polypeptide compounds, pharmaceutical compositions containing said compounds, and the use of said compounds as GIP-receptor agonists or antagonists for treatment of GIP-receptor mediated conditions, such as non-insulin dependent diabetes mellitus and obesity.

The invention relates to a method of imaging pancreatic β-cells, endocrine gastroenteropancreatic tumors and bronchial and thyroid neuroendocrine tumors and a method of treating endocrine gastroenteropancreatic tumors and bronchial and thyroid neuroendocrine tumors by targeting of glucose-independent insulinotropic polypeptide receptors (GIP receptors). Compounds considered are GIP or a GIP analog, each carrying a radionuclide, optionally complexed through a chelator. Non-radioactive GIP receptor antagonists as such are also considered in the long-term treatment of the mentioned tumors. The invention also relates to the use of a combination of GIP or a GIP analog, each carrying a radionuclide, with a GLP-1 agonist and / or somatostatin analogs, also carrying a radionuclide.

The present invention relates to trigonal GLP-1 / glucagon / GIP receptor agonists and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as for reduction of excess food intake.

The present invention provides fusion proteins comprising leptin and a second protein. The presence of the second protein provides increased biological activity and / or increased half-life in vivo. The present invention also provides human, canine and feline leptin molecules fused to peptides, antibodies or antibody fragments which enhances the abilities of the leptin molecules to transport through the blood-brain-barrier (BBB). The present invention also provides fusion proteins further comprising a peptide agonist that is capable of binding to and stimulate one, two or all three of the following receptors: GLP-1 receptor, Glucagon receptor, and GIP receptor. Also disclosed is a method of production such fusion proteins through recombinant technologies. The invention further discloses a pharmaceutical composition comprising one of the fusion proteins as an active intergradient as well as a method for using such a pharmaceutical composition to treat diseases in dogs, cats and humans.

The present invention provides a class of GLP-1 / GCG receptor dual agonist polypeptide compound. The GLP-1 / GCG receptor dual agonist polypeptide compound of the present invention can promote weight loss and prevent weight gain while more effectively lowering blood sugar , reverse insulin resistance, regulate lipid metabolism. The agonistic activity of the polypeptide compound of the present invention to GLP-1 receptor and GCG receptor is higher than the natural ligands of each receptor, and has lower agonistic activity to GIP receptor. The polypeptide compound provided by the invention has stable chemical properties and low immunogenicity, and is suitable as an active ingredient of medicines for treating metabolic diseases, such as diabetes, obesity, hyperlipidemia, NAFLD, and NASH.

Disclosed are peptide analogs derived from glucose dependent insulinotropic peptide (GIP), which are antagonists of the GIP receptor. These GIP peptide analogs are modified by comprising amino acid substitutions A13Aib and / or N24E and fatty acid conjugation is carried out with / without the use of linkers, thereby having improved solubility and / or physical stability.