58 results about "Recombinant GH" patented technology

The present invention proposes a growth hormone fusion protein and its application. The fusion protein includes an Fc mutant, which includes: a first peptide chain, wherein the first peptide chain 1) has a mutation at the following sites compared to the wild-type IgG4Fc fragment: at least one of the 234th, 235th, 298th, 299th, and 300th positions; or 231-239th positions; or 2) has a mutation at the following sites compared to the wild-type IgG1Fc fragment: at least one of the 228th-239th positions, and / or at least one of the 268th, 296th, 330th, and 331st positions. The fusion protein has a strong binding activity with human growth hormone receptors, can eliminate ADCC and CDC effects, promote Nb2-11 cell proliferation, and thus effectively treat or prevent diseases related to abnormal human growth hormone.

The invention provides a growth hormone fusion protein and application thereof. The fusion protein comprises an Fc mutant, the Fc mutant comprises an amino acid sequence as shown in SEQ ID NO: 49, or the Fc mutant comprises a first peptide chain and a second peptide chain, and the C end of the second peptide chain is connected with the N end of the first peptide chain; wherein a, compared with a wild type IgG4Fc fragment, the first peptide chain has the following mutations: F234V and L235E; or S298N, T299A, and Y300S, or a combination thereof; compared with a hinge region of wild type IgG4, the second peptide chain has S28P mutation; or b, compared with a wild type IgG4Fc fragment, the first peptide chain 1) has 231st-239th amino acid deletion; or (2) compared with a wild type IgG1Fc fragment, the IgG1Fc fragment has the following mutations: the 228th to 239th amino acid deletion, H268Q, Y296F, A330S and P331S. The fusion protein has high binding activity with a human growth hormone receptor, ADCC and CDC effects can be eliminated, Nb2-11 cell proliferation is promoted, and therefore human growth hormone abnormality related diseases are effectively treated or prevented.

A chemically modified human Growth Hormone (rhGH) prepared by attaching a transient linker which comprises a polyethylene glycol. The chemically modified protein may have a much longer lasting rhGH activity than that of the unmodified rhGH, enabling reduced dose and scheduling opportunities and the modified rhGH may not cause lipoatrophy. Also includes methods of use for the treatment and / or prevention of diseases or disorders in which use of growth hormone is beneficial.

The invention relates to the technical field of biological medicine, in particular to polypeptide for promoting release of growth hormone and application of the polypeptide, the polypeptide is shown as a formula (I), and in addition, the invention further provides application of the polypeptide shown as the formula (I) in preparation of medicine for diagnosing and / or treating diseases related to human growth hormone deficiency. Formula (I)

The present invention discloses a method for detecting human growth hormone based on a high-specificity double antibody sandwich method, including animal immunization, crude serum purification, serum fine purification, biomarkers, and human growth hormone content determination steps. The present invention establishes a method for detecting human growth hormone content, greatly improves the accuracy and technical requirements of the detected content, and provides a new detection method for medicine.

The present disclosure relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and their use in treating growth hormone deficiency or a condition associated with an abnormal reduction in growth hormone (GH) secretion in a subject that has adequate GH secretion potential.

The present disclosure relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and their use in treating growth hormone deficiency or a condition associated with an abnormal reduction in growth hormone (GH) secretion in a subject that has adequate GH secretion potential.

The invention belongs to the technical field of biological medicines, and relates to a method for promoting synthesis and secretion of growth hormones by bovine gland pituitary cells, in particular to a method for promoting synthesis and secretion of growth hormones by melatonin. In-vitro experiments show that the melatonin can improve the level of adenosine cyclophosphate in cells, promote phosphorylation of PKA protein, promote expression of FOXO1 protein, combine the FOXO1 protein with a promoter of a Gh1 gene and promote synthesis and secretion of growth hormone by combining melatonin receptors in bovine pituitary cells. The application value of the melatonin in the fields of animal growth promotion, growth hormone deficiency treatment and the like is shown.

The application discloses a method for preparing GHR humanized animal cells by using a CRISPR system, which comprises the following steps: designing and synthesizing sgRNA; mixing the sgRNA with a Cas9 protein to form a CRISPR-Cas9 complex; constructing donor DNA containing coding sequences of a human GHR extracellular region and a rat GHR intracellular region; injecting the CRISPR-Cas9 complex and the donor DNA into the cytoplasm or nucleus of a rat fertilized ovum to knockout the coding sequence of the extracellular region of the rat-derived GHR gene and simultaneously insert the coding sequence of the extracellular region of the human-derived GHR gene into the genome, so that the GHR humanized animal cells are obtained. The application further discloses a method for constructing a GHR humanized rat model by using the CRISPR system, and application of the GHR humanized animal cells and the GHR humanized rat model obtained by the above method in drug screening, drug development or efficacy evaluation. The application can more accurately simulate the interaction between the human GHR and growth hormone and other ligands, improves the accuracy and reliability of research, and has the advantages of simple gene editing operation, high editing efficiency, strong specificity, low off-target effect and wide application range.

The invention discloses a method for recombinant gene protein of sebastes schlegeli growth hormone, and belongs to the technical field of gene engineering. The sebastes schlegeli growth hormone gene is subjected to escherichia coli expression whole gene modification, and a label for 6Xhis purification is added; then, a recombinant escherichia coli (BL21 (DE3) / pET-28a) prokaryotic expression system is constructed, and sebastes schlegeli growth hormone fusion protein is expressed. The purified sebastes schlegeli growth hormone fusion protein is fed to fishes, and the average weight gain rate of the fishes is remarkably higher than that of a control group (Plt; 0.001), the average feed conversion ratio (FCR) is significantly reduced to 1.28 (Plt; the sebastes schlegeli growth hormone fusion protein prepared by the method provided by the invention has the advantages that the growth factor of the sebastes schlegeli growth hormone fusion protein is greatly improved, the feed utilization efficiency is obviously improved, the obtained sebastes schlegeli growth hormone fusion protein has a growth promoting effect, various risks caused by long breeding time are reduced, and the sebastes schlegeli growth hormone fusion protein shows a certain commercial application value.

The invention relates to two variable spliceosomes of a cynoglossus semilaevis adcyap1b gene and application of the two variable spliceosomes, and belongs to the technical field of functional gene screening and application in the aquatic biotechnology, the two variable spliceosomes are adcyap1b-tv1 and adcyap1b-tv2, coding region CDS sequences of the adcyap1b-tv1 and the adcyap1b-tv2 are SEQ ID NO: 1 and SEQ ID NO: 2, and protein sequences of the adcyap1b-tv2 are SEQ ID NO: 3 and SEQ ID NO: 4. The two variable spliceosomes of the adcyap1b gene are applied to regulation and control of hormone secretion of the pituitary of the cynoglossus semilaevis. By adding the recombinant protein of which the two variable spliceosomes are adcyap1b-tv1 and adcyap1b-tv2 into pituitary cells, the expression of a growth hormone gene gh, a prolactin gene prl, a growth lactin gene sl, a proogonin gene pomc and an adrenocorticotropic hormone release hormone gene crh of the cynoglossus semilaevis is regulated and controlled, so that the growth and development of the cynoglossus semilaevis are influenced.

Unidirectional SV40 late polyadenylation signals and combinations of such unidirectional SV40 late polyadenylation signals with other polyadenylation signals such as bovine growth hormone (BGH) polyadenylation signals are provided. The polyadenylation signals can be used in nucleic acid constructs and compositions that allow insertion of a coding sequence for a polypeptide interest into a target genomic locus and / or expression of the polypeptide interest. The nucleic acid constructs and compositions can be used in methods of integration of a coding sequence for a polypeptide interest into a target genomic locus and methods of expression of a polypeptide interest in a cell.

The present application relates to the technical field of biological medicine, in particular to a long-acting sustained-release human recombinant growth hormone fusion protein, a pharmaceutical composition and application thereof. The growth hormone fusion protein provided by the present application comprises a growth hormone and a temperature-sensitive elastin-like polypeptide. After subcutaneous injection of the fusion protein, phase transition occurs in situ at body temperature, and drug depots are formed. The drug is slowly released from the depots to the body circulation system, significantly prolonging the effective action time of a single injection of growth hormone, improving patient compliance, and improving pharmacokinetic parameters. The growth hormone fusion protein also has significantly improved biological stability and high biological activity, and has excellent application value and potential.

The invention belongs to the technical field of biological medicine and nano-drug delivery, and particularly relates to a long-acting growth hormone (hGH) wrapped bacterial outer membrane vesicle and application, and the outer membrane vesicle GH-OMVs wraps a human growth hormone mutant with an amino acid sequence shown as SEQ ID NO: 1. The GH-OMVs provided by the invention can be used for preparing medicines or preparations for preventing and / or treating diseases related to growth hormone deficiency or growth hormone-related metabolic disorder, including but not limited to growth hormone deficiency, dwarf / low height, osteoporosis and the like, and has a good clinical application prospect.

The invention belongs to the technical field of biological medicines, and particularly relates to an ovary-targeting drug carrier as well as a preparation method and application thereof. Specifically, the invention provides a targeted ovarian drug carrier ZIF-8-GH-ZP3, so as to realize targeted treatment of POI and targeted ovarian release of growth hormone to improve the treatment effect and reduce the adverse reaction of the growth hormone. According to the design of the drug carrier, a zeolite imidazole skeleton (ZIF-8) and a zona pellucida antibody (ZP3Ab) are adopted, growth hormones can be released in a targeted mode according to follicles developed at different levels in an ovary, targeted therapy of primary ovarian insufficiency is finally achieved based on the dual functions of targeting and promoting development of dominant follicles of the growth hormones, and the drug carrier has good practical application value.

The present disclosure relates, in general, to methods of treating short stature disorders in a subject who is non-responsive to growth hormone therapy using variants of C-type natriuretic peptide (CNP).

The present invention relates to a long-acting growth hormone or a pharmaceutical formulation comprising such long-acting growth hormone for use in a method of treating growth hormone deficiency with improved outcomes.

To provide compositions for use in treatment of diseases responsive to the use of human growth hormone receptor antagonists or other receptor antagonists.SOLUTION: The present invention provides a composition that is a human growth hormone receptor antagonist, comprising: a human growth hormone receptor antagonist G120K, wherein one or two amino acids of the human growth hormone receptor antagonist G120K have been mutated to cysteine; and a polyethylene glycol molecule conjugated to each substituted cysteine in the human growth hormone receptor antagonist G120K mutant.SELECTED DRAWING: None

Provided are a single-domain antibody specifically binding to a growth hormone (e.g., a human growth hormone) or an antigen-binding fragment thereof, a polypeptide construct and conjugate containing the single-domain antibody or the antigen-binding fragment thereof, a nucleic acid molecule encoding the single-domain antibody or the antigen-binding fragment thereof, a host cell containing same, and the related use. In addition, further provided is the use of the single-domain antibody or the antigen-binding fragment thereof, the polypeptide construct or the conjugate in the purification and / or detection of the growth hormone (e.g., the human growth hormone).

The invention relates to the field of biological medicine, and discloses application of an ENPP1 inhibitor in preparation of a medicine for treating pituitary growth hormone adenoma. The ENPP1 inhibitor is a compound with a structure as shown in a formula I, or an isomer, a derivative, a solvate or a pharmaceutically acceptable salt thereof. It is found for the first time that the ENPP1 inhibitor has a remarkable treatment effect on pituitary growth hormone adenoma, not only inhibits secretion of GH, but also inhibits growth of adenoma. Specifically, the inhibitor efficiently inhibits the activity of growth hormone adenoma cells ENPP1, inhibits adenoma cell proliferation and GH secretion in an in-vitro model, reduces the GH and IGF-1 levels of tumor-bearing mice in an in-vivo model, and is suitable for GH adenoma insensitive to somatostatin analogue drugs (such as octreotide). In addition, when the ENPP1 inhibitor is combined with octreotide for use, a synergistic effect is shown, and the anti-tumor effect is further enhanced.

The application belongs to the technical field of biological medicine, and particularly relates to a drug carrier targeting ovaries and a preparation method and application thereof. Specifically, the application provides a drug carrier ZIF-8-GH@ZP3 targeting ovaries, so that targeted treatment for POI is realized, growth hormone is released in a targeted manner to improve the treatment effect and reduce the adverse reactions of growth hormone. The drug carrier is designed by using a zeolite imidazole framework (ZIF-8) and a zona pellucida antibody (ZP3Ab), can release growth hormone in a targeted manner according to different levels of developing follicles in the ovaries, based on the dual functions of targeting and promoting the development of dominant follicles, finally realizes targeted treatment for primary ovarian insufficiency, and has good practical application value.

The present invention discloses a capsule composition including a series of components that are involved in cell regeneration, stimulate the growth hormone and help improve wrinkles and aging of the skin, repair cell DNA, and have antioxidant properties that prevent aging due to oxidative stress, detoxifying the body of toxins that accumulate over the years and nourishing cells. The composition of each capsule incorporates a combination of L-ornithine, L-arginine, N-acetylcysteine and other ingredients by means of precise dosing. After being absorbed by the human body, it can stimulate stable, natural secretion of HGH, thereby restoring the body's vitality and continuously producing collagen, hyaluronic acid to strengthen connective tissue, and make the skin firm and smooth.

The invention discloses a preparation method and application of an oral recombinant fusion fish growth hormone and a PEGylated fish growth hormone, and relates to the fields of gene recombination technology and pharmaceuticals. The amino acid sequence of the fusion fish growth hormone in the invention comprises a transduction protein domain sequence, a linker protein sequence and a universal fish growth hormone amino acid sequence. The invention adopts a Piscinenodavirus (PNV) transduction domain sequence, a Grass Carp Reovirus (GCRV) transduction domain sequence, and a Protein Kinase Activated Receptor 2 (Par2) TMhelix1 as a cell-penetrating peptide to guide the growth hormone into cells, thereby improving the protein transduction rate. Meanwhile, mPEG-NH2 is used to PEGylate the fusion protein, thereby improving the half-life of the fusion protein and making it suitable for use in juvenile fish.

The invention provides a marker for identifying aggressive behaviors of growth hormone type pituitary tumors and application of the marker, and belongs to the technical field of molecular biology. The marker provided by the invention comprises growth hormone or phosphorylated growth hormone. According to the invention, IGH-PitNETs tissue and plasma GHPs spectrums are drawn by using a 2DE-LC-MS technology, and it is found that specific GHPs exist in IGH-PitNETs. Experiments show that GH, GH-Ser77 phosphorylation and Ser176 phosphorylation are potential invasion biomarkers and treatment targets of GH-PitNETs, and an important theoretical basis is laid for clarification of a growth hormone type pituitary tumor invasion mechanism and development of a new clinical treatment approach.

The present invention provides a fusion polypeptide, the fusion polypeptide targeting both GLP-1 receptors (GLP-1R) and growth hormone receptors (GHR). The present invention provides polynucleotides encoding the fusion polypeptide, vectors expressing the fusion polypeptide and / or comprising the polynucleotides, as well as cells expressing the polynucleotides and / or comprising the vectors. The present invention also provides methods of preparing the fusion polypeptide and use of the fusion polypeptide in the manufacture of a medicament. Also provided are methods of treatment and fusion polypeptides for use in therapy.

Described herein is a new oral method for using MK-0677 for detecting growth hormone (GH) deficiency (GHD). Also described is a method of treating growth hormone (GH) deficiency (GHD) in children with a functional hypothalamic-pituitary GH axis.

This invention relates to the field of biomedical technology, and more particularly to a polypeptide that promotes the release of growth hormone and its applications, said polypeptide being as shown in formula (I). Furthermore, the application of the polypeptide shown in formula (I) in the preparation of medicaments for diagnosing and / or treating diseases related to human growth hormone deficiency is also provided. Formula (I).

A compound represented by formula I, a racemate, a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a polymorphic substance, a pharmaceutically acceptable salt or a prodrug thereof. The compound has a good GHSR1a agonist effect and can be used for diagnosing, treating or preventing diseases and diseases related to growth hormone deficiency or growth hormone dependence and preparing drugs for diagnosing, treating or preventing the diseases and diseases. # imgabs0 #

The present invention discloses a serum biomarker for screening or detecting growth hormone injection and its application; the serum biomarker includes 20 different metabolites, and by analyzing the expression of the metabolite group, it can be determined whether the sample has been injected with growth hormone. The present invention also provides a screening method for the biomarker group, which uses metabolomics technology to analyze human blood samples to obtain a metabolite combination related to growth hormone injection. The screening method of the present invention has wide universality, high accuracy, and good stability, and is expected to be used for screening growth hormone injection.

This invention discloses a recombinant human growth hormone-collagen fusion protein, its preparation method, and its applications, relating to the field of fusion protein technology. The fusion protein comprises a human growth hormone sequence and a human-like collagen sequence. The amino acid sequence of the fusion protein is shown in SEQ ID NO.7. The first homologous region of the human growth hormone is located at the N-terminus of the fusion protein, and the second homologous region of the human-like collagen is located at the C-terminus. In this invention, recombinant human growth hormone and human collagen with tissue repair function are fused through genetic engineering, achieving efficient expression in the periplasmic space in *E. coli*. High-purity products are obtained by GH affinity chromatography and weak cation exchange chromatography. The protein has a normal structure and good in vitro activity, and can be used to prepare long-acting growth hormone preparations or wound repair materials, showing significant clinical application prospects.