30results about "Parathyroid hormones" patented technology

The invention relates to the technical field of biology, in particular to a nucleic acid molecule, a carrier containing the nucleic acid molecule, a host cell, a pharmaceutical composition and application of the nucleic acid molecule and the carrier. The nucleic acid molecule provided by the invention is particularly suitable for application scenes of gene therapy and treatment of various diseases.

The present invention relates to variants of TEV protease that have—compared to the wildtype enzyme—increased stability and catalytic activity as well as altered substrate specificity. The invention further relates to compositions comprising these variants as well as uses thereof and methods in which these variants are employed.

A linker for linking a therapeutic agent to another moiety, such as the Fc region of an antibody. A linker having two or more maleimide functional groups capable of undergoing a nucleophilic conjugate addition reaction. A method for increasing the duration of action of a therapeutic agent by conjugating it to a novel linker and the Fc region of an antibody. An antibody-drug conjugate having an increased duration of action over the drug alone.

Fusion compounds and methods of using same are provided which bind and neutralize human receptor activator of nuclear factor kappa-B ligand and are agonistic to parathyroid hormone receptor 1 signaling, said compounds are useful as agents for bone healing or treating conditions associated with bone mass loss or degeneration including treating osteoporosis.

The invention relates to the field of biological medicine, relates to a bifunctional fusion protein and application thereof, and more specifically relates to a polypeptide construct containing an antigen binding domain capable of specifically binding to RANKL and PTH peptide, and related application of the polypeptide construct in disease treatment.

The present invention relates to the field of biomedicine. More specifically, the present invention relates to a polypeptide construct comprising an antigen binding domain capable of specifically binding to RANKL, and a PTH peptide, and a related use thereof for disease treatment.

Provided herein are methods of analyzing samples from batches of abaloparatide for abaloparatide and abaloparatide-related peptide impurities.

The application relates to the technical field of medicines, and discloses arginine glycosylation modified teriparatide and application thereof. First, a glycosylation donor is synthesized through a chemical synthesis method, then, according to a template PTH: SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF-NH2 amino acid sequence, arginines at positions 20 and 25 are replaced by ornithine with a Dde protecting group, the arginine glycosylation modified teriparatide is obtained by using the glycosylation donor to modify the same through a solid-phase synthesis method. The method is simple and easy to implement, has high purity and high yield. Further experiments prove that the arginine glycosylation modified teriparatide can significantly promote osteoblast differentiation, has high serum stability, and has potential application value in the treatment of diseases such as osteoporosis.

Disclosed are peptide-fatty acid conjugates, pharmaceutical compositions containing them, and methods of their medical use in the treatment of, e.g., a disease or condition associated with the PTHR1 signaling overactivity (e.g., hypercalcemia, hypophosphatemia, hyperparathyroidism, or Jansen's metaphyseal chondrodysplasia) or deficiency (e.g., hypoparathyroidism, hyperphosphatemia, osteoporosis, fracture repair, osteomalacia, arthritis, thrombocytopenia, or chronic kidney disease).

This invention relates to the field of biomedicine, disclosing a long-acting pTH polypeptide compound and its preparation and application. The polypeptide has an octadecanoic acid or eicosanoic acid and its derivatives modified by at least one amino acid residue at the 13th, 26th, and 27th amino acid residues of the pTH (1-34) parent peptide sequence, and is covalently bound to the polypeptide backbone via an AEEA-AEEA-γ-Glu linker. This invention significantly enhances the binding ability of the polypeptide to serum albumin and prolongs its half-life by utilizing fatty acid side chain modification. The long-acting pTH polypeptide compound of this invention exhibits significant osteogenic activity, promoting the proliferation of MC3T3-E1 cells and generating osteogenic markers and calcium nodules under osteogenic induction conditions, with a 2-6 fold increase in binding ability to serum albumin. This invention also provides a solid-phase synthesis method for this polypeptide compound and a pharmaceutical composition containing it, which can be used to treat osteoporosis and hypoparathyroidism, effectively solving the compliance problem of existing drugs requiring daily injections.

The invention belongs to the technical field of biology, and particularly relates to a human parathyroid hormone 1-34 peptide analogue and a preparation method and application of the human parathyroid hormone 1-34 peptide analogue, and the human parathyroid hormone 1-34 peptide analogue is formed by peptide fragments shown in SEQ ID No.1-SEQ ID No.8 or homologous peptide fragments of the peptide fragments. The human parathyroid hormone 1-34 peptide analogue has osteoporosis treatment activity, is used for relieving parathyroid hypofunction and related symptoms after parathyroid gland resection or extirpation, and also has an erection promoting function, and the preparation method is economical and environment-friendly, is suitable for industrial development and has a wide prospect.

This disclosure concerns production of product peptides with a target amino acid sequence by proteolysis of a recombinant polypeptide comprising specific protease recognition sites or chemical cleavage sequences. In some embodiments, the product peptide is released from repeating peptide units in the recombinant polypeptide by removal of intervening amino acid sequences by proteolysis by proteases that recognize sites within the intervening amino acid sequences and a carboxypeptidase, aminopeptidase, and / or further protease.

The application discloses a bone inductive active polypeptide capable of being assembled into nanofiber hydrogel and application thereof. The bone inductive active polypeptide comprises an assembly domain at a C terminal, a bone inductive active domain at an N terminal and a flexible connection separation domain between the two. The assembly domain is (RADA) 4‑9 The bone inductive active domain is parathyroid hormone (PTH) or parathyroid hormone related peptide (PTHrP). The bone inductive active polypeptide can be spontaneously assembled into a peptide nanofiber, and can be co-assembled into a peptide nanofiber hydrogel by mixing with RADA16 peptide. The hydrogel assembled from the bone inductive active polypeptide and the high-molecular composite nanobiomaterial constructed by the hydrogel can effectively avoid polypeptide burst release, avoid polypeptide degradation by local proteases, replace long-term systemic systemic administration of PTH and PTHrP, improve patient compliance and reduce patient pain. The application provides a new strategy for in-situ bone repair of PTH and PTHrP.

This invention discloses a method for targeted screening of teriparatide-producing bacteria using antibiotics. Through two rounds of screening with different concentrations of antibiotics, E. coli strains capable of high teriparatide expression are obtained, and the plasmid stability is effectively maintained during strain passage without the addition of antibiotics. This targeted screening method not only effectively improves the screening efficiency of high teriparatide-producing bacteria but also overcomes the technical difficulty of adding antibiotics during the production of biopharmaceuticals.

The present invention relates to the field of biomedicine, and more particularly, the present invention relates to a complex of PTH protein or an active fragment thereof and an antibody or a fragment thereof that specifically binds to PTH, and a related use thereof in disease treatment.

The invention relates to the technical field of polypeptide drugs, and provides a synthesis method of abparatide, which comprises the following steps: by taking Rink Amide AM resin, Rink MBHA resin or Rink Amide resin as a solid-phase carrier, sequentially coupling single amino acid and 19-21 tripeptide fragments or 19-22 tetrapeptide fragments from N terminal to C terminal through a solid-phase synthesis method according to a primary sequence of abparatide, so as to obtain abparatide peptide resin; the abparatide peptide resin is cracked to obtain abparatide, and a coupling agent / alkali adopted for coupling is selected from at least one of Oxyma / DIC, COMU / DIEA, COMU / TMP, PyOxim / DIEA and TPTU / DIEA. The abparatide crude peptide synthesized by the method disclosed by the invention is high in yield and high in purity, and the synthesis method disclosed by the invention shortens the production time, reduces the production cost and is beneficial to commercial production.

Disclosed herein are compounds and methods for treating osteogenesis imperfecta in individuals.In some embodiments, the compounds comprise bone anabolic agents, linkers and bone targeting ligands.In some embodiments, the methods comprise reducing the occurrence or likelihood of bone fracture, increasing bone density or bone strength, and providing compounds to the low density bone sites and weakened bone sites in individuals with osteogenesis imperfecta.

The invention belongs to the technical field of polypeptide liquid-phase synthesis carriers, and discloses a soluble liquid-phase carrier for polypeptide liquid-phase synthesis and application of the soluble liquid-phase carrier. The structural formula of the soluble liquid phase carrier for polypeptide liquid phase synthesis is shown in the specification, in the formula, 1-3 groups R are selected from H, methoxyl, halogen, alkyl, aldehyde group and nitryl; the number of the group Linker-Tag is 1 to 3; when the soluble liquid-phase carrier is applied to polypeptide liquid-phase synthesis, the soluble liquid-phase carrier not only shows excellent performance in the aspects of improving the operation efficiency, conveniently monitoring the reaction process and the like, but also has the advantages of economical efficiency and sustainable use, can remarkably improve the efficiency and controllability of the polypeptide liquid-phase synthesis process, and has extremely high practicability.

The invention discloses a long-acting parathyroid hormone receptor stimulant fusion protein and application thereof. The fusion protein can inhibit the activity of RANKL and promote PTHR-mediated bone anabolism, and comprises a first arm and a second arm, the first arm comprises a functional region targeting RANKL and an Fc region, and the second arm comprises a functional region capable of activating PTHR and an Fc region. The long-acting parathyroid hormone receptor stimulant fusion protein has the advantages of better drug effect, more lasting effect, better safety, higher structural stability, higher expression quantity and the like, and the comprehensive performance of the long-acting parathyroid hormone receptor stimulant fusion protein is superior to that of the existing or potential treatment means such as teriparatide, PEG-PTH, anti-RANKL monoclonal antibody, romomonoclonal antibody or a control sample synPTH-alpha RANKL-1.

Provided herein are methods of analyzing samples from batches of abaloparatide for abaloparatide and abaloparatide-related peptide impurities.

A recombinant PTH fusion protein, a construction method therefor, and an application thereof. The recombinant PTH fusion protein comprises: A1) at least one signaling domain molecule capable of activating a PTHR1 intracellular pathway; A2) a molecule having one or more ECDs capable of binding to the PTHR1; A3) a human serum albumin nanobody, wherein an amino acid sequence of the human serum albumin nanobody is as shown in SEQ ID NO: 7. The recombinant PTH fusion protein is capable of effectively improving the duration and magnitude of pharmacodynamic action, increasing blood calcium levels within 24-48 hours, and returning to normal levels within 48-72 hours. Said protein has excellent temperature stability and freeze-thaw stability, and can be used for treating and / or preventing hypoparathyroidism. In addition, the preparation method for the recombinant PTH fusion protein is simple and can be used for industrial production.

To provide a PTH prodrug or a pharmaceutically acceptable salt thereof, or a drug, for parathyroid hormone replacement therapy that enables alleviation of symptoms relating to hypocalcemia, hypercalciuria and hyperphosphatemia without causing hypercalcemia.SOLUTION: The present invention provides a PTH prodrug having the formula 31 in the figure or a pharmaceutically acceptable salt thereof. In the formula: PTH(1-34) is parathyroid hormone with a specific amino acid sequence; NαS1 is the α-amino group of the N-terminal serine in the specific amino acid sequence; and 2x10 kDa PEG includes a branched polyethylene glycol polymer with two arms each having a molecular weight ranging from 7.5 to 30 kDa.SELECTED DRAWING: None

The present invention provides a room temperature stable solution for injection comprising Abaloparatide and stabilizer selected from L – methionine, disodium EDTA, D-ɑ-tocopheryl polyethylene glycol succinate, hydroxypropyl betadex, mannitol, S- methyl-L- cysteine or a mixture thereof, wherein the solution is stable for at least 6 months when stored at 25 °C temperature and 60 % relative humidity Further, the present invention provides a process for the preparation of the said solution. The invention provides an injectable solution that is stable at room temperature which overcomes the limitations of the currently marketed formulation.

The present invention relates to the field of biomedicine, and more specifically, to a complex containing a PTH protein or active fragment thereof and an antibody or fragment thereof that specifically binds to PTH, and the related use thereof in the treatment of a disease.

The application discloses the technical field of polypeptide medicine preparation and relates to a synthesis method of abaloparatide, which comprises the following steps: step 1, according to the amino acid sequence of the main chain of abaloparatide from the C terminal to the N terminal, protected amino acids are sequentially coupled by a solid-phase synthesis method to obtain a peptide resin of C terminal 1#-33# amino acids; step 2, N terminal 1# Ala is coupled by the solid-phase synthesis method to obtain an abaloparatide peptide resin by using coupling conditions for avoiding carbamate acylation side reactions; and step 3, the abaloparatide peptide resin is cleaved to obtain a crude abaloparatide peptide. The coupling conditions for avoiding carbamate acylation side reactions used in step 2 are as follows: (1) using Ala with an alpha-amino group protected by double protection groups as a reaction raw material; and / or (2) using a combination of a phosphoric acid type condensation reagent and an organic base as a condensation system. The application is optimized from the idea of a carbamate acylation side reaction mechanism, effectively reduces the impurity of added Ala, and reduces the content of the impurity from 1.03% in the crude peptide before optimization to 0.05%.

The invention relates to the technical field of biology, in particular to a nucleic acid molecule, a carrier containing the nucleic acid molecule, a host cell, a pharmaceutical composition and application of the nucleic acid molecule and the carrier. The nucleic acid molecule is particularly suitable for gene therapy and can be applied to the scene of treatment of various diseases.

Aiming at the long-term challenges that recombinant parathyroid hormone (PTH1-34) is difficult to express, easy to degrade and high in cost in escherichia coli, a brand-new fusion protein framework is designed: efficient secretion is ensured through a signal peptide SP6, high solubility and stable expression are realized by utilizing an optimized special soluble protein tag, and then the parathyroid hormone (PTH1-34) is obtained through an exquisite linker sequence. And purifying and releasing the target active polypeptide PTH1-34. According to the technical scheme, the expression quantity of the fusion protein is greatly improved, protease degradation of host bacteria is effectively resisted, the yield of PTH1-34 is remarkably improved, and the production cost is greatly reduced. The optimized strain is subjected to induced expression for 16 hours, the expression quantity of the fusion protein reaches 39.2%, the thallus yield is 167g / L, and the fermentation yield of the fusion protein is 22g / L, which is increased by at least 400 times compared with 50mg / L in the prior art; the stable, efficient and large-scale production of the therapeutic polypeptide is realized.

The invention discloses a parathyroid hormone related peptide analogue as well as a preparation method and application thereof. The analogue comprises any one or more than two peptides in 40 sequences. The parathyroid hormone-related peptide analogue disclosed by the invention not only shows a remarkable anti-osteoporosis effect in a zebra fish osteoporosis model, but also shows good characteristics in pharmacokinetic property research in a rat body, and the effect of a part of compounds is superior to or equivalent to that of a positive control drug, namely, aspartatide. Part of candidate polypeptides are superior to aspartatide in the aspects of availability, half-life period and the like, and have the advantages of quicker effect taking, stronger targeting property and less dosage required for maintaining the curative effect. The results provide a solid experimental basis for the PTHrP analogue as a medicine for preventing and / or treating osteoporosis, and show potential clinical application value of the PTHrP analogue.

The invention relates to the technical field of biology, in particular to a nucleic acid molecule, a carrier containing the nucleic acid molecule, a host cell, a pharmaceutical composition and application of the nucleic acid molecule and the carrier. The nucleic acid molecule is particularly suitable for gene therapy and can be applied to the scene of treatment of various diseases.