34 results about "Human growth hormone" 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 discloses a human growth hormone detection antibody and a preparation method thereof. The amino acid sequence of the detection antibody is one of SEQ ID NO. 1 and SEQ ID NO. 2; the preparation method comprises the following steps: extracting RNA (Ribonucleic Acid), performing reverse transcription, amplifying obtained cDN A, inserting into escherichia coli, and constructing a human growth hormone primary library; the M13KO7 auxiliary bacteriophage invades the human growth hormone primary library to construct a bacteriophage primary library; carrying out three rounds of solid phase panning on the phage primary library, and carrying out monoclonal screening, ELISA detection and sequencing to obtain a target gene sequence; and synthesizing the target gene sequence into a prokaryotic expression plasmid, introducing the prokaryotic expression plasmid into escherichia coli, and adding IPTG for expression to obtain the detection antibody. The detection antibody has the characteristics of low economy, strong stability and simple subsequent operation, and solves the problem that animal immunization is always needed to prepare the antibody in the subsequent process in human growth hormone detection.

This invention relates to treating Prader-Willi Syndrome (PWS) using a KATP channel opener. The channel opener may be coadministered with other therapies used to treat PWS, such as human growth hormone, a wakefulness promoting agent, or a psychiatric or mood stabilizing drug, thereby allowing the baseline dosages of these other therapies to be decreased or making these other therapies unnecessary. The invention also relates to treating PWS based on the PWS nutritional phase of a patient, to prevent the patient's PWS nutritional phase from progressing or shift the patient's PWS nutritional phase back to an earlier phase. The invention further relates to treating PWS, and conditions associated with low basal metabolic rate or hyperphagia, with the KATP channel opener based on a patient's blood ketone levels.

The invention relates to the field of biological immunity and pharmaceutical preparations, and particularly discloses a human growth hormone (GH) freeze-drying protective agent. The invention further discloses a freeze-drying preparation prepared from the freeze-drying protective agent. The freeze-drying preparation mainly comprises the following components in parts by weight: 10-100 mM of a buffer solution, 1-30 parts of a protective agent, a stabilizer and an excipient, 0.01-1.5 parts of a surfactant, 0.1-0.8 part of an antioxidant and 0.05-3 parts of a preservative. The invention provides a specific preparation method of the freeze-dried preparation, the preparation has the advantages of long preservation period, short redissolution time compared with a common reagent, good form and good structural stability after freeze-drying, provides favorable protection conditions for preparation of ELISA standard substances and internal control substances, is beneficial to maintenance of the stability of proteins, and has good application prospects. The specificity and the sensitivity of the ELISA kit are improved.

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.

The present invention belongs to the field of bioengineering technology, and specifically relates to a human growth hormone fusion protein and its application. The fusion protein hGH-linker-HSA and the hGH mutant fusion protein hGHmutF31Q / V90E-linker-HSA are constructed by connecting hGH and HSA through a connecting peptide. Mouse experiments show that hGHmutF31Q / V90E-linker-HSA can improve the metabolic stability of hGH, prolong the half-life of hGH, and enhance the administration effect of hGH, and has a broad application prospect in clinical practice.

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 embodiments of the present disclosure provide method for Detecting the Biological Activity of Recombinant Human Growth Hormone Medicine. The result of biological activity detection method for GH medicine provided in present disclosure is stable and reliable. The operation is simple. The experimental period is short. there is no need for cells or other components from human primary tissue sources. The specificity and accuracy are high. The method can be used for product development and release inspection. It avoids cell contamination and errors caused by long-term incubation and multi-step operations. The color result is stable and the quality is controllable. The biological activity of GH medicine detected by the method is correlated with clinical efficacy, providing important reference for the treatment of related diseases in clinical practice.

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 invention belongs to the technical field of biological medicines, and discloses a novel long-acting recombinant human growth hormone fusion protein. The fusion protein is obtained by fusion expression of human growth hormone (hGH) and an anti-human albumin nano antibody (VHH). And the long-acting principle is that the clearance rate is reduced by reversibly and widely combining with albumin with endogenous circulation. The fusion protein has the characteristics that 1, the fusion protein is obtained by fusion expression of two functional domains of hGH and VHH, hGH sequence mutation and complex chemical modification are not involved, the preparation method is simpler, and the sample uniformity is better; 2, in the fusion protein, the N end of the hGH protein has no additional structure, and the VHH functional domain is connected to the C end of the hGH, so that the influence on the activity of the hGH is reduced; and 3, animal efficacy results show that the fusion protein has a long-acting effect.

The present disclosure relates to the use of C-terminal fragments of human and non-human growth hormone, synthetic cyclic peptides and C-terminal fragments of human prolactin precursor for the treatment of inflammatory airway disease in a subject in need thereof.

The invention discloses a quantitative analysis method and device for stable isotope labeled recombinant human growth hormone, and belongs to the technical field of quantitative analysis of protein, the method comprises the following steps: S1, preliminarily measuring the purity of stable isotope labeled recombinant human growth hormone based on chromatography or electrophoresis; s2, on the basis of preliminarily determining the purity of the stable isotope labeled recombinant human growth hormone in the step S1, measuring the stable isotope labeled amino acid replacement efficiency through amino acid analysis-isotope dilution mass spectrometry; and S3, based on the stable isotope labeled amino acid replacement efficiency, measuring the content of the stable isotope labeled recombinant human growth hormone through peptide fragment quantitative analysis-isotope dilution mass spectrometry. According to the method, the isotope dilution mass spectrometry is adopted to eliminate system errors possibly introduced in the pretreatment step and the measurement process, and the accuracy and credibility of the measurement result can be remarkably improved. According to the method, traceable quantitative analysis of the content of the stable isotope labeled recombinant human growth hormone can be realized, and the measurement result can be traced to the international system of units.

This invention provides single-domain antibodies or antigen-binding fragments thereof that specifically bind to growth hormone (e.g., human growth hormone), polypeptide constructs and conjugates containing said single-domain antibodies or antigen-binding fragments thereof, nucleic acid molecules encoding said single-domain antibodies or antigen-binding fragments thereof, and host cells containing them, as well as related uses. Furthermore, it provides uses of said single-domain antibodies or antigen-binding fragments thereof, polypeptide constructs, or conjugates for the purification and / or detection of growth hormone (e.g., human growth hormone).

The present invention relates to the field of vectors, in particular to recombinant viral vectors suitable for in vivo delivery of therapeutic genes. Described is an adeno-associated virus (AAV) vector comprising (i) a human growth hormone intron 3 (hGHi3) sequence, (ii) a synaptic promoter sequence and / or (iii) a granulin precursor 3'untranslated region (UTR) sequence operatively linked to a polynucleotide sequence encoding a polypeptide of interest. Particular uses of such vectors are to enhance the expression of a polypeptide of interest, such as a granulin precursor (PGRN), to treat subjects having gene mutations or intrinsic polypeptide levels below physiologically normal levels.

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 present application relates to a kind of Fc mutant, fusion protein, nucleic acid molecule, expression vector, recombinant cell, pharmaceutical composition and its purposes.Fc mutant has the amino acid sequence as any one of SEQ ID NO:3~7;Fusion protein includes: second peptide segment, second peptide segment is the functional region of bioactive molecule, third peptide segment, third peptide segment includes the amino acid sequence shown in SEQ ID NO:2 or the Fc mutant of preceding, second peptide segment is connected with third peptide segment.The Fc mutant of the present application is monomer form, fusion protein has higher in vitro and in vivo activity and lower ADCC, CDC effect, can effectively treat growth hormone deficiency.

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 provides a novel nano antibody-based recombinant long-acting human growth hormone fusion protein, nucleic acid, a pharmaceutical composition, application and the like. Existing long-acting means of PEGylation, Fc fusion and the like often cause reduction of activity, the human growth hormone is innovatively fused with an anti-albumin nano antibody with a specific sequence, and protein with larger molecules is formed through combination of the nano antibody and albumin antigen, so that the half-life period of the human growth hormone is prolonged, the activity of the human growth hormone is prolonged, and the human growth hormone can be used for preparing the anti-albumin nano antibody. In addition, the activity of the fusion protein provided by the invention is higher than that of a human growth hormone standard substance. The fusion protein and the like have wide industrial application prospects in the field of biological medicines.

A method for treating growth hormone deficiency, including administering a human growth hormone fusion protein (GX-H9). A method includes administering a pharmaceutical composition containing an hGH fusion protein (GX-H9) and a pharmaceutically acceptable carrier, wherein the fusion protein (GX-H9) is administered once a week at a dose of 0.4 to 1.6 mg per body weight kg of a pediatric patient, or administered once every two weeks at a dose of 0.8 to 3.2 mg per body weight kg of a pediatric patient.

The invention discloses an affinity chromatography method for purifying human growth hormone and a DARPin dimer ligand. The DARPin dimer comprises a first DARPin monomer and a second DARPin monomer which are connected through a connecting peptide or a disulfide bond; each DARPin monomer is provided with a four-section type structure of an N-cap, a first internal repeated module IR1, a second internal repeated module IR2 and a C-cap; the amino acid sequence of the DARPin monomer is selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5 in a sequence list, and the amino acid sequence of the DARPin monomer has 90%-98% sequence identity with any amino acid sequence selected from the list. According to the present invention, through the design of the DARPin dimer ligand having the N-cap, the first internal repeating module IR1, the second internal repeating module IR2 and the C-cap four-segment structure, and the directed random mutation of the IR1 / IR2 region, the novel ligand having high affinity and high specificity on the human growth hormone is obtained, and the non-specific binding of the host protein and the structure-similar impurities is significantly reduced;

A combination of medications and medication doses is disclosed whereby age-related changes in systemic inflammation, cancer risk, heart disease risk, CD38 expression, hair color, thymotrophic hormones, immune cell populations, the CD4 / CD8 cell ratio, bone marrow density, thymus structure, kidney function, and epigenetic age can be reversed in humans. Surprisingly, agents that accelerate the growth of cells reduce cancer risk, agents that intensify immune responses attenuate age-related inflammation, agents with no prior connection to hair color reverse age-related hair whitening, and a combination of agents that induces IGF-1, a hormone previously thought to drive systemic aging, results in a reversal of systemic aging as documented by an epigenetic clock. Medication combinations useful in the present invention include human growth hormone (GH) or GH releasers, dehydroepiandrosterone (DHEA), and metformin.

The invention relates to the technical field of biological medicine, in particular to a recombinant human growth hormone injection preparation and application thereof. The recombinant human growth hormone injection preparation provided by the invention has the advantages that the pH value is close to the human physiological pH value, the stability is good, the activity is high, byproducts such as endogenous toxins are few, the transportation and the storage are convenient, and the clinical use is more convenient, easier and safer; in addition, the recombinant human growth hormone injection preparation is simple in preparation method and has important market popularization value.

Provided are a method for administering a recombinant human growth hormone GX-H9 for treating growth hormone deficiency and a pharmaceutical composition containing a recombinant human growth hormone GX-H9 and a pharmaceutically acceptable carrier. The method includes administering recombinant human growth hormone GX-H9 once a week with a dosage of 0.1 to 0.3 mg per weight kg of a patient or twice-monthly with a dosage of 0.1 to 0.4 mg per weight kg of the patient.

Described herein are growth hormone receptor antagonists and modified growth hormone receptor antagonists. The growth hormone receptor antagonists and the modified growth hormone receptor antagonists are useful in the treatment of diseases or conditions responsive to human growth hormone receptor antagonists, such as cancer and acra hypertrophy.

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).

The utility model discloses a recombinant human growth hormone liquid medicine distribution device, and relates to the technical field of recombinant human growth hormones. The device comprises a collecting box, wherein a quantifying mechanism and a stirring mechanism are arranged on the collecting box; the outer wall of the collecting box is fixedly connected with a plurality of supporting legs, the top of the collecting box is communicated with a feeding pipe, the right side of the collecting box is communicated with a discharging pipe, the top of the discharging pipe is communicated with a quantifying pipe, and the quantifying mechanism comprises a quantifying assembly I and a quantifying assembly II; the first quantifying assembly comprises two adaptive circular rings fixedly connected to the inner wall of the discharging pipe, and two cross-shaped supporting frames are fixedly connected to the inner wall of the discharging pipe. By arranging the quantifying mechanism, the problems that the dosage of liquid medicine given each time is greatly fluctuated due to inconvenience in quantification, and a doctor is difficult to accurately evaluate the treatment effect and cannot adjust the treatment scheme in time due to the uncertainty of the dosage are solved.

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.

The application discloses a kind of recombinant cyclic human growth hormone-Fc fusion protein and application thereof.The fusion protein is sequentially connected by Fc fragment, human growth hormone, Fc fragment from N-terminal to C-terminal using two connection peptides to form a molecule, and forms a pair or more pairs of disulfide bond or does not form disulfide bond after the folding of two Fc fragments, to constitute cyclic Fc-hGH-Fc.The refolding ratio of the cyclic Fc-hGH-Fc fusion protein is higher than the yield of monomer Fc / Fc-hGH expression refolding, and the form of Fc / Fc homodimer and double body hGH-Fc / hGH-Fc is less, which is convenient for later purification.The fermentation preparation process of the fusion protein of the application is simple, convenient for purification, high in yield and low in cost.The fusion protein of the application weakens the protein clearance effect caused by growth hormone receptor by using the steric hindrance effect of Fc, further prolongs the half-life of drug and increases the efficacy.

Disclosed herein is a method for manufacturing a recombinant human growth hormone (h GH) modified by a CTP extension in a mammalian cells culture system.