88results about "Parathyroid hormones" patented technology

The invention relates to the field of biological medicine, and discloses a pTH long-acting polypeptide compound as well as preparation and application thereof. According to the polypeptide, at least one amino acid residue of the 13th, 26th and 27th amino acid residues of a pTH (1-34) parent peptide sequence is connected with octadecanedioic acid or eicosanoic acid and a derivative modification group of octadecanedioic acid or eicosanoic acid, and the polypeptide is covalently combined with a polypeptide skeleton through an AEA-AEA-gamma-Glu connecting unit. The binding capacity of the polypeptide and serum albumin is remarkably enhanced by utilizing a fatty acid side chain modification means, and meanwhile, the half-life period is prolonged. The pTH long-acting polypeptide compound disclosed by the invention has remarkable osteogenic activity promoting effect, can promote proliferation of MC3T3-E1 cells and generate osteogenic markers and calcium nodules under osteogenic induction conditions, and the binding capacity of the pTH long-acting polypeptide compound and serum albumin is improved by 2-6 times. The invention further provides a solid-phase synthesis method of the polypeptide compound and a pharmaceutical composition containing the polypeptide compound, the polypeptide compound can be used for treating osteoporosis and parathyroid hypofunction, and the compliance problem that an existing medicine needs to be injected every day is effectively solved.

The invention discloses a method for synthesizing dipeptide Fmoc-Leu-Aib-OH, and belongs to the field of polypeptide synthesis, the specific preparation method comprises the following steps: under the action of organic alkali and an activating reagent, Fmoc-Leu-OH and H-Aib-OH react to obtain the dipeptide Fmoc-Leu-Aib-OH; the activating reagent comprises at least one of N, N, N ', N'-tetramethyl chloroformamidine hexafluorophosphate, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethyl urea hexafluorophosphate and benzotriazole-1-yl-oxytripyrrolidinyl phosphorus hexafluorophosphate, and the organic base comprises at least one of N-methylimidazole, N, N-diisopropylethylamine and pyridine. The dipeptide Fmoc-Leu-Aib-OH prepared by the preparation method disclosed by the invention is high in yield, high in purity and high in raw material conversion rate.

To provide a method for management and / or treatment of hypoparathyroidism (HP) in a subject.SOLUTION: A method comprises the step for administering a dose of a circulating parathyroid hormone (PTH) compound having a specific amino acid sequence to a subject, where administration of the PTH compound maintains or improves bone integrity.SELECTED DRAWING: None

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.

The invention discloses a preparation method of dipeptide Fmoc-Leu-Aib-OH, and belongs to the field of polypeptide synthesis, the specific preparation method comprises the following steps: under the action of organic alkali and an activating reagent, Fmoc-Leu-OH and H-Aib-OH react to obtain the dipeptide Fmoc-Leu-Aib-OH; the activating reagent comprises at least one of N, N, N ', N'-tetramethyl chloroformamidine hexafluorophosphate, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethyl urea hexafluorophosphate and benzotriazole-1-yl-oxytripyrrolidinyl phosphorus hexafluorophosphate, and the organic base comprises at least one of N-methylimidazole, N, N-diisopropylethylamine and pyridine. The dipeptide Fmoc-Leu-Aib-OH prepared by the preparation method disclosed by the invention is high in yield, high in purity and high in raw material conversion rate.

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 present invention relates to parathyroid hormone (PTH) variants and pharmaceutical compositions comprising the same. The present invention further relates to PTH compositions having improved serum half-life and peak-to-trough ratio and methods for controlling serum calcium levels using the PTH variants and compositions of the present invention. The present invention further relates to methods for treating hypoparathyroidism and / or hypocalcemia caused by hypoparathyroidism using the PTH variants and compositions of the present invention.

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.

Provided is a PTH1 ligand-bound nucleic acid complex that is delivered to a desired organ and that is for regulating the expression or editing of a target gene, a transcript thereof or a translation product thereof.　This PTH1 ligand-bound nucleic acid complex, which has a structure wherein a PTH1 ligand is bound to a nucleic acid, said nucleic acid containing an antisense strand containing an oligonucleotide that has a nucleic acid base sequence complementary to a target transcript and that comprises 12-30 nucleotides, is delivered to an organ and regulates the expression or editing of a target gene, a transcript thereof or a translation product thereof, which makes the complex useful in treating a disease caused by the gene. Further, the ligand-bound nucleic acid complex can be delivered to organs, tissues and cells in which PTH1 receptors are expressed, for example tissues such as that of the kidney, bones, and subcutaneous fat, and cells such as vascular endothelial cells, which makes the complex useful in treating diseases in these organs.

The present invention relates to field of protein expression. It provides expression constructs and methods for increased expression of recombinant proteins. More particularly, it provides constructs and methods for enhanced expression of Lira-peptide in a recombinant host cell.

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.

The invention relates to parathyroid hormone (PTH) variants and pharmaceutical compositions comprising same. The invention further relates to PTH compositions with improved serum half-life and peak-trough ratios, and methods of controlling serum calcium levels with the PTH variants and compositions of the invention. The invention further relates to methods of treating hypoparathyroidism and / or hypocalcemia due to hypoparathyroidism with the PTH variants and compositions of the invention.

The present invention relates to peptide modifier compounds of Formula (1), or a salt thereof, wherein: a is an integer from 1 to 10, more preferably from 1 to 3; b is an integer from 0 to 7; Z is a terminal group and Y is a bivalent group. Further aspects of the invention relate to intermediates in the preparation of compounds of Formula (1), and the use of compounds of Formula (1) in the synthesis of peptide derivatives.

The present invention relates to the field of medicine and, in particular, to the production of large amounts of soluble recombinant polypeptides as part of a fusion protein, said fusion protein comprising an N-terminal fusion partner linked to a target polypeptide.

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

PTH prodrugs and pharmaceutical compositions containing such PTH prodrugs are provided. The present invention relates to a compound represented by formula (Ia) or (Ib) TIFF2022068210000086.tif3247 (wherein -D is a PTH moiety, and -L 1 - is a reversible prodrug linker moiety linked to the PTH moiety -D by a functional group of PTH, and -L 2 - is a single chemical bond or spacer moiety; -Z is a water soluble carrier moiety; x is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16; and y is an integer selected from the group consisting of 1, 2, 3, 4, and 5, or a pharmaceutically acceptable salt thereof.

To provide an oral formulation of parathyroid hormone analog.SOLUTION: The present invention relates to method of preventing or treating disease or disorder comprising administration of oral pharmaceutical composition comprising therapeutically effective amount of parathyroid hormone (PTH) analog and at least one degradation preventing agent, wherein said composition provides relative bioavailability of at least 0.5%, compare to subcutaneous administration. The present invention also relates to the oral pharmaceutical composition comprising therapeutically effective amount of PTH analog and least one degradation preventing agent in physically separated dosage form and wherein said PTH analogue is in enteric coated form. At least one degradation preventing agent includes combination of at least one metal containing compound and at least one reducing agent where in at least one metal containing compound is selected for group consisting of vanadium containing compound, chromium containing compound and manganese containing compound. Preferably PTH analogue are teriparatide or abaloparatide.SELECTED DRAWING: Figure 1

This invention relates to the use of probiotic yeast cells that produce recombinant parathormone for therapeutic purposes, where probiotic cells that produce rhPTH developed for use in hypoparathyroidism treatment are first microencapsulated, placed into gelatin capsules and then orally administrated.

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.

To provide novel collagen-binding therapeutic agents targeting collagen.SOLUTION: A collagen-binding therapeutic agent comprises: two collagen-binding domains linked by a domain linker, and a therapeutic agent linked to at least one of the collagen-binding domains by a therapeutic agent linker, where the collagen-binding agent lacks collagenase activity, and where one of the two collagen-binding domains is selected from a group consisting of polypeptides having specific sequences and the other of the collagen-binding domains is selected from a group consisting of polypeptides having specific sequences.SELECTED DRAWING: Figure 1A

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).

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 protein engineering technology, and discloses a recombinant PTH fusion protein and a construction method and application thereof. The recombinant PTH fusion protein comprises: A1) a signaling domain molecule having at least one domain that can activate the intracellular pathway of PTHR1; A2) a molecule having one or more ECDs that can bind to PTHR1; A3) a human serum albumin nanobody; wherein the amino acid sequence of the human serum albumin nanobody is shown in SEQ ID NO.7. The recombinant PTH fusion protein of the present invention can effectively improve the duration and intensity of drug efficacy, can increase blood calcium within 24 to 48 hours, and return to normal within 48 to 72 hours, and has excellent temperature stability and freeze-thaw stability, and can be used to treat and / or prevent hypoparathyroidism. In addition, the preparation method of the recombinant PTH fusion protein of the present invention is simple and can be used for industrial production.

The present technology generally relates to a method for management and / or treatment of hypoparathyroidism (HP) in a subject. The method comprises administering a dose of a PTH compound to the subject, wherein the PTH compound has an amino acid sequence as set forth in SEQ ID NO: 10; and wherein administration of the PTH compound maintains or improves bone integrity.

To provide a more convenient and safer treatment of hypoparathyroidism with reduced side-effects.SOLUTION: The present invention provides a pharmaceutical composition comprising at least one controlled-release PTH compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH. The pharmaceutical composition is administered once every 24 hours or less frequently at a dosage of the controlled-release PTH compound that corresponds to 70% or less of the molar equivalent dose of PTH 1-84 administered every 24 hours required to maintain serum calcium within normal levels over the 24-hour period in humans.SELECTED DRAWING: None

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.