291results about "Fibroblast growth factor" patented technology

Provided are a GLP-1GIP analog, an FGF21 protein, a trifunctional protein, and use thereof. The trifunctional protein comprises the GLP-1 / GIP analog and the FGF21 protein. Further provided is use of the GLP-1 / GIP analog, the FGF21 protein, and the trifunctional protein in the preparation of a drug for preventing and / or treating diseases related to GLP-1, GIP, and / or FGF21. The provided GLP-1 / GIP analog, FGF21 protein, and trifunctional protein can synergistically regulate blood glucose and lipid levels in vivo, meet multiple needs in patients with type 2 diabetes, including lowering blood glucose, alleviating hepatic steatosis, promoting weight loss, ameliorating circulating lipid metabolism disorder, etc., and have better biological safety and tolerability and longer in vivo half-lives.

The invention discloses a GLP-1 GIP analogue, an FGF21 protein, a three-function protein and an application thereof. The trifunctional protein comprises a GLP-1 / GIP analogue and an FGF21 (Fibroblast Growth Factor 21) protein. The invention also discloses application of the GLP-1 / GIP analogue, the FGF21 protein and the three-function protein in preparation of medicines for preventing and / or treating diseases related to GLP-1, GIP and / or FGF21. The GLP-1 / GIP analogue, the FGF21 protein and the three-function protein provided by the invention can synergistically regulate blood sugar and lipid levels in vivo, meet multiple requirements of patients with type 2 diabetes for reducing blood sugar, relieving liver fatty degeneration, reducing weight, improving circulating lipid metabolism disorder and the like, and are better in biological safety and tolerance and longer in in-vivo half-life period.

A dual function protein is disclosed. The dual function protein may be prepared by linking a biologically active protein and an FGF mutant protein to an Fc region of an immunoglobulin. The dual function protein has improved pharmacological efficacy, in vivo duration and protein stability. The dual function protein exhibits improved pharmacological efficacy, in vivo duration and protein stability. A pharmaceutical composition containing the dual function protein as an active ingredient may be effectively used as a therapeutic agent for diabetes, obesity, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis or cardiovascular diseases.

The present disclosure relates to methods of treating, preventing or managing cardiovascular and / or metabolic disorders selected from the group consisting of hypercholesteremia, dyslipidemia, hypertriglyceridemia, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), type 2 diabetes and obesity in a human subject in need thereof by administering a human FGF21 protein variant.

According to various aspects of this disclosure, the present disclosure relates to methods for reducing kidney inflammation, reducing kidney fibrosis, reducing oxidative stress in the kidney, preventing or reducing the likelihood of chronic kidney disease (CKD), treating or preventing acute kidney injury (AKI) or treating a kidney disease in a subject in need thereof comprising administering, e.g., intramuscularly, to the subject a recombinant adeno-associated virus (rAAV) vector, wherein the rAAV vector comprises a vector genome comprising a nucleotide sequence encoding a Fibroblast growth factor 21 (FGF21) or a functional fragment thereof and an AAV capsid (e.g., AAV1 serotype), optionally, wherein the subject does not suffer from diabetes.

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

Provided are use of FGF21 polypeptide, FGF21 fusion protein or dual-fusion protein of FGF21 polypeptide and GLP-1 or a functional variant thereof in the manufacture of a medicament for treating fatty liver-related diseases.

The present invention relates to a chemically modified adeno-associated virus (AAV), a method for preparing the same, and its use in gene therapy. The chemically modified AAV is preferably prepared by incubating the AAV with a chemical reagent having an N-substituted luminol moiety under conditions conducive to reaction of the chemical reagent with tyrosine residues exposed on the surface of the AAV capsid, preferably by electrochemical methods.

To provide: a method for producing a complicated peptide molecule, such as a dimeric peptide, in a simpler manner at lower cost compared with the conventional chemical synthesis methods; a dimeric peptide which comprises a specific short linker and has a satisfactory activity; and others.SOLUTION: A peptide molecule comprises: (I) a first physiologically active peptide portion; (II) a linker portion composed of 49 or less amino acid residues; and (III) a second physiologically active peptide portion located on the opposite side of the linker portion from the first physiologically active peptide portion, wherein the first physiologically active peptide portion and the second physiologically active peptide portion may be the same as or different from each other, and at least 90% of an amino acid sequence of the linker portion is composed of amino acid residues selected from alanine (A), proline (P), and serine (S).SELECTED DRAWING: None

The present disclosure provides for a synthetic immunogenic protein for use as an immuno-modulatory agent to enhance mammalian immune reactions towards conjugated protein or peptide containing antigens that are otherwise poorly immunogenic, including but not limited to self-antigens. The chimeric immunogenic proteins of the present disclosure can be used in the treatment of many illnesses, including but not limited to cancers, infectious disease, autoimmune disease, allergies and any clinical indication involving or affected by the immune response of a mammalian host.

The present invention belongs to the field of biopharmaceuticals, and particularly relates to a multi-domain active protein for treating metabolic diseases. The multi-domain active protein has a structural formula as shown in Formula I: A-L a -F-L b -B. Compared with the prior art, the multi-domain active protein of the present invention has a long half-life and supports a once-weekly dosing frequency; the GLP-1R agonist activity of the multi-domain active protein is increased by more than 200 times at most; the multi-domain active protein has good stability in vivo and in vitro and low immunogenicity; since no unnatural amino acids need to be introduced and no chemical synthesis and cross-linking steps are involved, it can be prepared by a recombinant method, greatly simplifying the preparation process.

Provided herein are polynucleotides comprising a coding sequence for expression of a fibroblast growth factor 21 (FGF21) pathway activating agent. Also provided are vectors, recombinant viral genomes, and recombinant virus compositions comprising said polynucleotides, as well as associated methods.

A long-acting FGF21 derivative, specifically relating to an FGF21 derivative comprising an FGF21 mutant protein and a fatty acid chain. The FGF21 derivative, which is obtained by coupling the fatty acid chain to a cysteine residue at position 172 of an FGF21 protein by means of a linker, has relatively high FGF21 activity, and has a better weight loss effect in model mice. The FGF21 mutant protein not only retains the activity of mature FGF21, but also has significantly improved stability in serum.

The invention relates to a thermostable FGF10 polypeptide possessing FGF10 activity and having or comprising at least 85% sequence identity to SEQ ID NO:3 that has or comprises an amino acid sequence from Ser69 to Ser208 of SEQ ID NO:1, or to SEQ ID NO:5 that has or comprises an amino acid sequence from Leu40 to Ser208 of SEQ ID NO:1, or the fragments thereof, comprising at least an amino acid substitution L152F. Preferably, any of amino acid substitutions V123I, Q175E, and N181D can be further included. The invention further discloses the use of subjected thermostable FGF10 polypeptides in regenerative medicine or other related medical applications or cosmetics. Further, it discloses a culture medium comprising subjected thermostable FGF10 polypeptides suitable for proliferation and differentiation of the human embryonic stem cells or formation and differentiation of spheroids and organoids.

Compositions, methods and treatment regimens for mutant fibroblast growth factor-21 (FGF-21) peptide conjugates for the treatment of severe hypertriglyceridemia are provided.

The present invention relates to an isolated polypeptide, or a functional fragment thereof, having at least 85% sequence identity to SEQ ID NO: 12, comprising an amino acid substitution at position C113, preferably C113A.5

The invention relates to the technical field of biological medicines, in particular to a preparation method of a stem cell factor composition for promoting scalp hair follicle regeneration. The method comprises the following steps: performing high-low oxygen cycle pre-stimulation and stepped hypoxia induction on umbilical cord mesenchymal stem cells, monitoring secretion kinetics of vascular endothelial growth factors (VEGF), hepatocyte growth factors (HGF), keratinocyte growth factors (KGF) and fibroblast growth factors 2 (FGF2) in real time, and determining the optimal collection time; performing ultrafiltration on the supernate to obtain a primary concentrated solution, optimizing the molecular weight cutoff based on the bioactivity retention rate after freezing and thawing, and concentrating to obtain a stem cell factor concentrated solution; the stem cell factor composition is obtained by combining the stem cell factor with a compound nutrition preparation, verifying in-vitro hair follicle cell proliferation / migration activity, dynamically adjusting the nutrition proportion according to the relative efficiency ratio and optimizing. According to the invention, intelligent preparation of the stem cell factor composition with multi-factor synergistic secretion, controllable process, stable activity and adjustable functions is realized.

A production method for a cell aggregate containing a retinal tissue having a layer structure, the method comprising performing suspension culturing or adhesive culturing of a dispersed retinal cell population in a medium containing a Wnt signal transduction pathway acting substance, wherein the retinal cell population includes at least one type of cells selected from the group consisting of retinal precursor cells and photoreceptor precursor cells.

The invention provides a recombinant human basic fibroblast growth factor based on AI (artificial intelligence) design and a construction method of an expression vector of the recombinant human basic fibroblast growth factor, which are characterized in that on the basis of an AI artificial intelligence algorithm, a high-stability recombinant human basic fibroblast growth factor protein configuration is designed through AI aided design and mutation of protease easily-hydrolyzed sites of a human fibroblast growth factor 2, and the expression vector of the recombinant human basic fibroblast growth factor is constructed. And the high-stability human fibroblast growth factor 2 recombinant vector is constructed and prepared, so that the biological activity of the FGF2 is improved, and the durability of the drug effect is facilitated. According to the invention, the amino acid screening range can be reduced by 50-80%, the medicine research and development cycle can be shortened by 1 / 4-1 / 5, and the research and development cost can be reduced by 10-20%. And the protein drug screening efficiency is improved.

Provided is a technology whereby a heterologous protein can be expressed in a bacterium which does not have an endogenous Tat system secretion machine. The present specification discloses a bacterium that is selected from the group consisting of bifidobacteria, lactococci, and staphylococci and has been modified to express a heterologous Tat protein. The bacterium has the ability to produce and secrete a heterologous protein.

The invention belongs to the technical field of exosomes, and particularly relates to an engineered exosome for overexpressing EGF and FGF as well as a preparation method, a product and application of the engineered exosome. An LAMP2B fusion expression technology is adopted, EGF and FGF are directionally anchored to the surface of a 293T cell source exosome membrane, free factor degradation is avoided, and the problem that the carrying amount of natural exosome factors is insufficient is solved. Through the synergistic effect of two factors, the exosome can reverse proliferation inhibition of DHT on hair follicle hair papilla cells, improve the cell migration ability, promote AGA mouse hair follicles to recover from a resting period to a growing period and block hair follicle microminiaturization, and finally reconstruct an AGA hair follicle microenvironment to achieve functional hair growth. Cell experiments confirm that the compound can repair hair follicle cells damaged by DHT, animal experiments show that the AGA mouse hair coverage rate is increased, the safety is good, the primary clinical effect is achieved, an efficient, safe and flexible new scheme is provided for AGA treatment, and the compound has good clinical transformation potential.

The application discloses preparation of a canine fibroblast growth factor 21 fusion protein and application thereof in treating atopic dermatitis. The application provides a caninized fibroblast growth factor 21 (FGF21) fusion protein, which is composed of a caninized fibroblast growth factor 21 (FGF21) and a fusion tag, and the fusion tag is TAT or R11 or Fc. The three kinds of FGF-21 fusion proteins obtained by the application can effectively improve the symptoms of atopic dermatitis of mice and reduce the expression level of related inflammatory factors. The three kinds of FGF-21 recombinant fusion proteins provided by the application can be used as potential drugs for treating atopic dermatitis of dogs.

Therapeutic regimens and uses of mutant fibroblast growth factor-21 (FGF-21) peptide conjugates in the treatment of non-alcoholic steatohepatitis are provided.

A nonviral gene therapy delivers DNA that allows cells to produce proteins such as their own growth factors in culture media. Lipid nanoparticles provide an effective delivery mechanism into a target cell. By encapsulating plasmid DNA encoding the growth factors with inducible promoters into lipid nanoparticles (LNPs), target cells create their own growth factors reducing a need for expensive growth factors from external sources. DNA expression lasts for several days reducing the amount of reagent needed. The plasmid DNA is more stable than mRNA and proteins, therefore reducing logistical challenges.

This invention provides a thermostable hbFGF mutant and a method for its efficient expression in Escherichia coli. By mutating five amino acid sites of wild-type hbFGF (D15I / C78S / C96Y / S137P / K128N) to improve thermostability, optimizing molecular design, constructing an expression vector, and transforming the expression strain of Escherichia coli, efficient and soluble expression of hbFGF in Escherichia coli is achieved.

The present application relates to a CRISPR-mediated immortalized sheep fetal skin fibroblast cell line in the field of variation or genetic engineering and application thereof.The construction of the CRISPR-mediated immortalized sheep fetal skin fibroblast cell line of the present application comprises the following steps: step one, constructing a Cas9 site-directed knockout plasmid containing an FGF5 gene target sequence; step two, constructing a homologous repair plasmid Donor-2 kb HA-SV40LT containing an FGF5 gene homologous arm; step three, constructing a donor DNA containing an SV40LT protein expression frame; and step four, preparing a sheep fetal fibroblast cell line stably expressing SV40LT protein.The immortalized SFF-FGF5 / SV40LT monoclonal cell strain created by the present application can become an ideal tool cell line for genome editing researches such as sheep CRISPR library screening, multiple gene editing and mutation gene function exploration.

The present invention discloses a recombinant human FGF4 protein, which is an amino acid sequence as shown in SEQ ID NO: 1, 2, 3 or 4, or a protein derived from the above amino acid sequence by substitution, deletion or addition of one or several amino acids and having the activity of a recombinant human FGF4 protein; the activity of the protein provides a function capable of promoting keratinocyte migration. The present invention also discloses the use of the recombinant human FGF4 protein or a composition thereof in the preparation of a drug or kit capable of promoting keratinocyte migration and promoting skin wound recovery. The present invention discovered through in vivo and in vitro pharmacological experiments that the recombinant human FGF4 protein (rFGF4) can promote keratinocyte migration, significantly promote the healing of acute wounds and chronic diabetic wounds, and improve the quality of wound healing. Therefore, FGF4 can be prepared for use in skin wounds, especially chronic, refractory wounds.

Fusion polypeptides are provided that include a nanobody and FGF21 linked by a polypeptide linker. Fusion polypeptides are also provided that include GLP-1, a nanobody, and FGF21, each linked by two polypeptide linkers. Fusion polypeptides are also provided that include a functional moiety conjugated to the FGF2. Liquid pharmaceutical compositions containing the same and methods for treating diseases using the same are also provided.

The problem that this invention aims to solve is to improve hFGF23 antagonist compounds. [Solution] The present invention relates to a novel hFGF23 antagonist polypeptide, its long-acting derivatives, and its use in pharmaceuticals, and more particularly to inhibiting hFGF23-induced signaling in patients who require it, such as patients suffering from hypophosphatemic disorders like X-linked hypophosphatemic rickets (XLH), and pharmaceutical compositions containing such compounds.