36 results about "Agonist peptide" patented technology

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Such retro-Michael resistant composition is generally achieved by conformational modification of the albumin, resulting in stereoselective coupling of the linker to the albumin.

A pharmaceutical composition comprises a GPCR agonist fusion protein wherein the GPCR agonist peptide is covalently conjugated to an albumin via a linker in a manner that is resistant to a reverse Michael addition. Advantageously, the compositions presented herein avoid uncoupling of the agonist to the albumin while maintaining the agonist and the albumin in a spatial relationship that allows efficient binding and activation of the GPCR while also enabling gp60-mediated endocytosis transport and FcRn-mediated albumin recirculation. These characteristics enable ultra-low doses of GPCR agonist fusion proteins to produce therapeutic effects while significantly reducing or even completely avoiding side effects that would otherwise be typically associated with unbound agonists. Such reverse Michael resistant compositions are typically achieved by conformationally modifying an albumin, resulting in a stereoselective coupling of a linker to the albumin.

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Moreover, these properties also enable transport of the GPCR agonist fusion protein across the blood brain barrier and therefore allow treatment of neural disorders.

Provided are novel compounds for GIPR, GLP-1R and GCGR. Specifically, provided are GLP-1R / GIPR / GCGR triagonists peptides, and conjugates comprising an Fc fragment and GLP-1R / GIPR / GCGR triagonists peptides. Pharmaceutical compositions comprising these compounds,as well as uses thereof in treating metabolic conditions and disorders, such as diabetes mellitus, type 2 diabetes, obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and non-alcoholic steatohepatitis (NASH) are also provided.

To provide GLP-1R agonistic peptides with reduced GLP-1R agonistic activity, fusion molecules comprising the same and pharmaceutical compositions.SOLUTION: The invention provides a GLP-1R agonistic peptide whose GLP-1R agonistic activity is about 9- to about 531-fold reduced as compared to the GLP-1R agonistic activity of native GLP-1 of a specific sequence. The invention also provides a nucleic acid molecule encoding GLP-1R agonistic peptide with reduced GLP-1R agonistic activity, a pharmaceutical composition comprising a GLP-1R agonistic peptide with reduced GLP-1R agonistic activity and combinations thereof. The pharmaceutical composition is for treating obesity, overweight, metabolic syndrome, diabetes, diabetic retinopathy, hyperglycemia, dyslipidemia, non-alcoholic steatohepatitis (NASH) and / or atherosclerosis.SELECTED DRAWING: None

The present application provides protease resistant glucagon-like peptide 1 (eGLP-1) peptides, as well as protease resistant dual agonist peptides directed against GLP-1R and GIPR, methods of making these peptides, as well as compositions comprising the protease resistant peptides and methods of treatment utilizing these peptides.

The present disclosure relates to a pharmaceutical formulation suitable for sublingual administration for use in the treatment of obesity, type II diabetes, or related diseases. The pharmaceutical formula comprises 5 to 10 milligrams of glucagon-like peptide-1 receptor agonist peptide (GLP-1 RA-P) which is dissolved in 1.5 to 2.0 milliliters of a buffer solution, and the pH (Potential of Hydrogen) value of the pharmaceutical formula is 5.5 to 7.5. The disclosure also discloses a method for treating obesity, type II diabetes, or related diseases. The method comprises administering the pharmaceutical formulation of the present disclosure to a subject in a sublingual administration, and allowing the pharmaceutical formulation to be continuously located sublingually of the subject for 5-10 minutes, where the pharmaceutical formulation has a bioavailability for GLP-1 RA-P of 2-10% compared to the administration to the subject through subcutaneous injection.

Hydrochloride salt forms of synthetic C-terminal peptide analogs of C5a, which are response selective agonists of C5aR-bearing antigen presenting cells. Methods of inducing an immune response in a subject by administering such peptide analogs alone or in combination with other active agents are also disclosed.

The present invention relates to GIP / GLP1 agonist compositions. The present invention is a GIP / GLP1 co-agonist peptide pharmaceutical composition for subcutaneous injection. The composition comprises tirzepatide, NaCl, and disodium hydrogen phosphate. The composition provides commercially acceptable shelf-life stability, use-life stability, and an acceptable patient injection site experience. An alternative composition comprises tirzepatide, propylene glycol, and disodium hydrogen phosphate, which also provides acceptable shelf-life stability.

The present invention relates to immunoglobulins, such as immunoconjugates, comprising an ActRII receptor antibody and a GLP-1 agonist molecule, such as a GLP-1 agonist peptide. Such constructs are useful in the treatment of numerous diseases and disorders, including metabolic disorders such as obesity, diabetes, and others.

This invention belongs to the field of peptide medicine, specifically relating to a compound as a TGF-β receptor agonist peptide and its uses. The amino acid sequence of the peptide is shown in SEQ ID No. 1. The peptide of this invention has a significant agonistic effect on the TGF-β receptor and can be used in the preparation of drugs for the prevention and / or treatment of TGF-β-related diseases, particularly for the prevention of hair loss and / or the promotion of hair growth.

GLP-1 and glucagon dual agonists disclosed herein have improved biological stability, including proteolytic stability, and duration of action. The peptides can be administered about once a week.

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Moreover, these properties also enable transport of the GPCR agonist fusion protein across the blood brain barrier and therefore allow treatment of neural disorders.

To provide fusion proteins with optimized GLP-1R agonist / FGF21 compound activity ratio.SOLUTION: The invention relates to a fusion protein comprising a glucagon-like peptide 1 receptor 5 (GLP-1R) agonistic peptide and a variant of human fibroblast growth factor 21 (FGF21). The invention further relates, in particular to the use of a fusion protein comprising a GLP-1R agonistic peptide and a variant of FGF21 as a medicament for treating obesity, overweight, metabolic syndrome, diabetes, diabetic retinopathy, hyper glycemia, dyslipidemia, non-alcoholic steatohepatitis (NASH) and / or atherosclerosis in a subject. The invention further relates to pharmaceutical compositions comprising a fusion protein comprising a GLP-1R agonistic peptide and a variant of FGF21.SELECTED DRAWING: None

G protein-coupled receptor (GPCR) agonist peptides and their use are described. Also described are vectors for expressing the GPCR agonist peptides and method for treating a disease or disorder with the GPCR agonist peptides.

To provide a GIP receptor agonist peptide compound having an activating action on a GIP receptor.SOLUTION: To provide a new peptide compound containing an amino acid sequence represented by a specific sequence and having activation action on a GIP receptor, and to provide use of the peptide compound as a medicine.SELECTED DRAWING: None

A pharmaceutical composition comprises a GPCR agonist fusion protein wherein the GPCR agonist peptide is covalently conjugated to an albumin via a linker in a manner that is resistant to a reverse Michael addition. Advantageously, the compositions presented herein avoid uncoupling of the agonist to the albumin while maintaining the agonist and the albumin in a spatial relationship that allows efficient binding and activation of the GPCR while also enabling gp60-mediated endocytosis transport and FcRn-mediated albumin recirculation. These characteristics enable ultra-low doses of GPCR agonist fusion proteins to produce therapeutic effects while significantly reducing or even completely avoiding side effects that would otherwise be typically associated with unbound agonists. In addition, these properties also enable GPCR agonist fusion proteins to transport across the blood-brain barrier, and thus allow for the treatment of neurological disorders.

To provide glucagon (Gcg) and GLP-1 dual agonist peptides useful in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and / or nonalcoholic steatohepatitis (NASH).SOLUTION: Provided is a compound having the following formula.SELECTED DRAWING: None

The present invention provides for purification of Tirzepatide using selective ion- pairing agents in the reversed phase-high performance liquid chromatography, for purifying crude Tirzepatide from closely related impurities.

The application discloses a multifunctional immunoregulatory fusion protein, a preparation method thereof, NK cells expressing the protein and application of the protein. The fusion protein structure is anti-CD16a VHH-(GGGGS)3-anti-NKG2D VHH-(EAAAK)2-IL-15R beta super agonist peptide, and the amino acid sequence is SEQ ID NO:1. The anti-CD16a VHH and the anti-NKG2D VHH synergistically activate immune effector cells, the IL-15R beta super agonist peptide strongly activates effector cells and weakly activates Tregs, and the linker ensures that the functions of the domains are independent. The protein can be efficiently prepared, the yield is 155 mg / L, the purity is higher than 95%, the NK cells and CD8 + T cells can be significantly activated, the 24h lysis rate of the protein on various tumor cells reaches 87.0%-90.0% in vitro, the tumor growth is significantly inhibited in vivo, the inhibition rate is 81.3%, and the survival period of tumor-bearing mice is prolonged by more than 60 days. The stability of the NK cells expressing the protein is improved after being treated by MI-3, and the protein provides a high-efficiency and safe candidate drug for tumor immunotherapy.

The invention discloses a multifunctional immunomodulatory fusion protein, a preparation method thereof, an NK cell for expressing the protein and application. The structure of the fusion protein is anti-CD16a VHH-(GGGGS) 3-anti-NKG2D VHH-(EAAAK) 2-IL-15R beta super agonist peptide, and the amino acid sequence of the fusion protein is SEQ ID NO: 1. Wherein the anti-CD16a VHH and the anti-NKG2D VHH synergistically activate the immune effector cells, the IL-15R beta super agonist peptide strongly activates the effector cells and weakly activates the Treg, and the linker ensures that each structural domain is independent in function. The protein can be efficiently prepared, the yield is 155mg / L, the purity is more than 95%, NK cells and CD8 + T cells can be obviously activated, the in-vitro cracking rate of various tumor cells in 24 hours reaches 87.0-90.0%, the in-vivo tumor growth is obviously inhibited, the inhibition rate is 81.3%, and the lifetime of tumor-bearing mice is prolonged by more than 60 days. The stability of NK cells expressing the protein is improved after MI-3 treatment, and efficient and safe candidate drugs are provided for tumor immunotherapy.

This invention belongs to the field of peptide medicine, specifically relating to a TGF-β receptor agonist peptide and its uses. The amino acid sequence of the peptide is shown in SEQ ID No. 1. The peptide of this invention has a significant agonistic effect on the TGF-β receptor and can be used in the preparation of drugs for the prevention and / or treatment of TGF-β-related diseases, particularly for the prevention of hair loss and / or the promotion of hair growth.

The present invention relates to a pharmaceutical composition to be used in the prevention or treatment of diseases involving vascular fibrosis. Specifically, the pharmaceutical composition according to the present invention contains a peptide that reduces fibrosis of perivascular tissue or the extracellular matrix constituting the vascular wall, and is useful for preventing or treating diseases involving vascular fibrosis, particularly pulmonary arterial hypertension.

G protein-coupled receptor (GPCR) agonist peptides and their use are described. Also described are vectors for expressing the GPCR agonist peptides and method for treating a disease or disorder with the GPCR agonist peptides.

Provided herein are chimeric multi-agonist peptides having agonistic function at melanocortin receptor (MCR), glucagon like peptide (GLP-1), and glucose-dependent insulinotropic polypeptide receptor (GIP-R) receptors.

This disclosure provides corticotropin releasing factor receptor 2 (CRFR2) agonist peptides, pharmaceutical compositions comprising such peptides, and methods of using such peptides to treat and / or prevent, for example, cardiovascular diseases, obesity, diabetes, sarcopenia, cachexia, kidney disease, heart failure and pulmonary hypertension.

To provide a simple method of dosing at a therapeutic dose to control blood glucose levels and / or induce weight loss without the need for titration to reach a therapeutic level in the absence of gastrointestinal side effects.SOLUTION: A liquid pharmaceutical dosage formulation is provided comprising an agonist peptide product selected from any one of the specific sequence groups, wherein the peptide is modified with a non-ionic glycolipid surfactant, and at least 0.66 milligrams of polysorbate 20 per milligram of peptide in the liquid pharmaceutical dosage formulation.SELECTED DRAWING: Figure 1

This invention provides a triple agonist peptide compound that activates three receptors: GLP-1R, GIPR, and GCGR. This peptide compound exhibits strong target activation efficacy and excellent hypoglycemic, lipid-lowering, and weight-controlling effects. It also provides the application of this peptide compound in the treatment of metabolic-related diseases, especially type II diabetes and related diseases.

The present disclosure relates to methods for treating or preventing obesity and other metabolic disorders in diabetic and non-diabetic subjects using combination therapy comprising a therapeutically effective dose of an antagonistic antigen binding molecule that specifically binds to the human glucagon receptor (GCGR) co-administered with a therapeutically effective low dose of glucagon like peptide- 1 receptor (GLP-1 R) agonist peptide approved for treating T2DM or using a bifunctional fusion molecule comprising a glucagon like peptide- 1 receptor (GLP-1 R) agonist peptide fused directly to an antagonistic antigen binding molecule that specifically binds to the human glucagon receptor (GCGR).

Provided are dual-target agonist peptides, and more specifically a series of dual-target agonists capable of simultaneously activating the human glucagon-like peptide-1 (GLP-1) receptor and the human glucose-dependent insulinotropic polypeptide (GIP) receptor, as well as pharmaceutical salts and pharmaceutical compositions thereof. These peptides have dual agonist effects and can be used to treat diabetes, obesity, and other related diseases.