269results about "Insulins" patented technology

The present application relates to the field of biomedicine, and specifically provides an acylated human insulin analogue, a pharmaceutical composition thereof and a preparation method therefor, and a method for using the acylated human insulin analogue or the pharmaceutical composition thereof to treat metabolic diseases.

Relaxin (RLN) analogs are disclosed that include modifications that increase half-life compared to native human RLN, maintain selectivity for the RXFP1 receptor, and provide stability in vitro and in vivo, improving druggability and reducing immunogenicity. Pharmaceutical compositions are also disclosed that include one or more of the RLN analogs described herein in a pharmaceutically acceptable carrier. Methods of making and using the RLN analogs are also disclosed, particularly for treating cardiovascular, pulmonary, and / or renal conditions, diseases, or disorders.

The invention discloses a synthesis method of an insulin analogue, which comprises the following steps of: firstly, obtaining A-chain peptide resin by using a solid-phase synthesis method, constructing a disulfide bond between A6 and A11 on a solid phase, and cracking the A-chain peptide resin by using a cracking solution containing a sulfydryl activator to obtain a peptide chain with an activated sulfydryl group and a protected sulfydryl group; then a solid-phase synthesis method is used for obtaining B-chain peptide resin, Lys side chain protecting groups are removed on a solid phase in a fixed-point mode, side chain fatty acid modification is completed, and a peptide chain with an exposed sulfydryl group and a protected sulfydryl group is obtained after cracking is conducted through a cracking solution; and mixing the products in a solution according to a certain proportion to form a first pair of intermolecular disulfide bonds, and constructing and purifying the last pair of disulfide bonds to obtain the insulin analogue. The method disclosed by the invention has the advantages of convenience in synthesis, low cost, simple process and the like, can be used for research on amino acid mutation of insulin compounds, and has important practical significance on development of insulin drugs.

Provided are a new acylated insulin, a pharmaceutical preparation thereof, a pharmaceutical composition thereof containing a long-acting GLP-1 compound, and the medical use of the acylated insulin, the pharmaceutical preparation and the pharmaceutical composition.

Provided are β-eliminative linkers suitable for the conjugation of small molecule, peptide, and protein and compounds comprising the linkers.

The invention provides a preparation method and application of a long-acting insulin analogue, and the preparation method comprises the following steps: taking eicosandioic acid A as a starting raw material, carrying out unilateral esterification with trimethylsilyl ethanol to obtain an intermediate B, reacting the intermediate B with Hosu to obtain an active intermediate C, reacting the intermediate C with L-glutamic acid-1-trimethylsilyl ethyl ester to obtain an intermediate D, and carrying out condensation reaction on the intermediate D to obtain the long-acting insulin analogue. The intermediate D reacts with Hosu to obtain an active intermediate E, the intermediate E reacts with AEEA-AEA to obtain an intermediate F, the intermediate F reacts with Hosu to obtain an active intermediate G, and trimethylsilylethyl is removed from the intermediate G through tetrabutylammonium fluoride trihydrate to obtain the Ecobainsulin side chain. The route of the method has the following advantages that related raw materials are simple and easy to obtain, the reaction condition is mild, the yield is high, and the method is suitable for industrial production. The preparation method is simple and easy to implement, large-scale production is easy, the prepared side chain of the Ekoinsulin and A14E, B16E, B25H and DesB30 insulin precursors are coupled with lysine at the B29 site under the alkaline condition to obtain a crude Ekoinsulin product, and the crude product is subjected to two-step purification to obtain the Ekoinsulin with the purity of 99.0% or above.

The present invention relates to novel insulin derivatives and their use in the treatment or prevention of medical conditions associated with diabetes. The insulin derivatives are glucose sensitive and show glucose sensitive albumin binding. The present invention also relates to novel intermediates. Finally, the present invention provides pharmaceutical compositions comprising the insulin derivatives of the present invention, and the use of such compositions in the treatment or prevention of medical conditions associated with diabetes.

Aspects of the disclosure include an implantable composition / medical device encapsulating insulin-producing cells for use in the treatment and management of diabetes, generally comprising a multilayer lattice structure fabricated from a continuously bioprinted cell-laden core / shell fiber, the lattice structure having a defined infill density and at least coating applied to the lattice post-printing, and preferably at least one conformal coating. In this way, multilayer lattice structures are provided with improved stability, retrievability, and functionality.

The present disclosure provides recombinantly manufactured ultra-long acting insulin-Fc fusion proteins for use in treating canine and feline diabetes. The insulin-Fc fusion proteins comprise an insulin polypeptide linked via a peptide linker to an Fc-fragment of canine or feline origin. Based on the results obtained, creating a treatment that is amenable to low cost manufacturing, exhibits sufficient in vivo bioactivity, displays extended duration of bioactivity, does not induce anti-drug antibodies, and substantially retains is potency over multiple administrations, requires a non-obvious combination of insulin polypeptide, peptide linkers, and species-specific Fc fragment, in addition to selective mutations on one or more of these components. Exemplary ultra-long acting insulin-Fc fusion proteins, polynucleotides encoding these insulin-Fc fusion proteins, and pharmaceutical formulations of exemplary insulin-Fc fusion proteins are provided, in addition to methods of use and preparation.

The present disclosure relates to a combination therapy comprising a first AAV vector genome comprising an insulin expression cassette; and a second AAV vector genome comprising a glucokinase expression cassette; wherein the first AAV vector genome and the second AAV vector genome are in a ratio selected from the group consisting of 1:0.25-0.75, 1:1.75-2.25, and 1:3.75-4.25, and methods for using the same for treating diabetes.

The present invention relates to a process of flocculation to purify recombinant proteins from crude fermentation broth of insulin and insulin analogs or derivatives at a manufacturing scale in the presence of urea and TritonX-100 at a specific pH. The flocculation process is followed by at least one centrifugation and pH adjustment step to further clarify the broth. It is further followed by a filtration step to finally remove any aggregates present, and a chromatography step to capture the pure protein. Using this process, a high product recovery rate of more than 95% has been achieved.

The present invention relates to novel insulin derivatives and their use in the treatment or prevention of medical conditions relating to diabetes. The insulin derivatives are glucose sensitive and display glucose-sensitive albumin binding. The insulin derivatives have a long half-life. The invention also relates to novel intermediates. Finally, the invention provides a pharmaceutical composition comprising the insulin derivatives of the invention and the use of such a composition in the treatment or prevention of medical conditions relating to diabetes.

Provided herein are engineered insulin polypeptide that exhibit disrupted cross-β fibrillation and pharmaceutical compositions comprising the polypeptides. The disclosure also provides are methods for making the insulin polypeptide. Also included are methods of using the pharmaceutical compositions to treat diabetes and hyperglycemia.

The present invention relates to a method for producing a recombinant protein by using a PDI derived from Trichoderma sp. strain. A variant yeast comprising a gene that encodes a PDI derived from Trichoderma sp. (the genus Trichoderma) strain, of the present invention, highly expresses a target protein, and thus is used to produce a target recombinant protein at a high yield.

The present disclosure relates to toxin-derived delivery constructs, in particular isolated non-naturally occurring delivery constructs, for oral delivery, comprising a bacterial toxin-derived delivery construct coupled to a biologically active therapeutic cargo; wherein the delivery construct is capable of delivering a bioactive cargo through epithelial cells via endocytotic transport; and wherein the delivery construct does not comprise a bacterial toxin-derived translocation domain or a bacterial toxin-derived catalytic (cytotoxic) domain.

Provided herein are methods for generating a protein product, comprising: providing a plant seed; contacting said plant seed with a protein expression vector that encodes for a protein; transiently expressing said protein in said plant seed using said protein expression vector, and isolating said protein from said plant seed to obtain a protein product.

To provide neoantigens and uses thereof.SOLUTION: Disclosure herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. The use of immunotherapeutic compositions is also disclosed. Novel immunotherapeutic agents and uses thereof are disclosed herein based on the finding of neoantigens generated from individual tumor-specific mutations. Thus, the disclosure provides peptides, polynucleotides encoding the peptides and peptide binding agents that may be used for stimulating immune response toward tumor associated antigen or neoepitopes, or for creating immunogenic compositions or cancer vaccines for use in disease treatment.SELECTED DRAWING: None

This application provides an insulin analogue and its use, the insulin analogue comprising an A chain and a B chain; the sequence of the A chain includes: GIVEQCCTSICSLX aa14 QLENYCN, the B-chain sequence contains: FVNQHLCGSHLVEALY aa16 LVCGEY aa22 GF Y aa25 YTPY aa29 Y aa30 ; where X aa14 Selected from E, Y, K, or D, Y aa16 Selected from Y or H, Y aa22 Selected from Q, S, T, Y, or N, Y aa25 Selected from F, H, or K, Y aa29 Let R and Y be... aa30 It does not exist; the condition is: X aa14 and Y aa25 There is only one K in the insulin analogue. The insulin derivative obtained by the above-mentioned insulin analogue has significantly better in vitro INSR phosphorylation activity and glucose uptake activity than the control drug Icodec. The efficacy (PD) was evaluated using a type 1 diabetic rat model. It has the potential to be administered once a week or less frequently and has a significant hypoglycemic effect.

Provided herein are compositions, systems, kits, devices, and methods comprising peptides of interest, mixture of individual amino acids, an aqueous solution, and uses thereof. The methods comprising peptides of interest may be characterized as methods of synthesizing a peptide. These peptides of interest may be characterized as hydrophobic or partially hydrophobic. These individual amino acids may be characterized as natural amino acids or unnatural amino acids. The aqueous solution may be characterized as pure or substantially pure water. Various compositions, systems, kits, devices, or methods of the present disclosure may involve synthesizing a peptide of interest from a template peptide.

The disclosure relates to the field of gene therapy for the treatment of an osteosarcoma using splice-switching oligonucleotides. Increased expression of INSR-A, an isoform frequently expressed in cancer, can effectively evade current therapeutic mechanisms and contribute to resistance in cancer patients. As a means to address the ability of cancer to evade therapies through this mechanism, Applicant provides a polynucleotide comprising a promoter, for example a U7 or a U1 promoter, and a first splice-switching oligonucleotide (SSO) that targets a regulatory element of an insulin receptor (JR).

The disclosure relates to novel compounds that include one or more aromatic boron-containing groups, including diboronates, and methods of making the disclosed compounds. The present disclosure further relates to pharmaceutical compositions comprising the disclosed compounds, and their use in prevention and treatment of diseases and disorders, such as hyperglycemia, type 2 diabetes, impaired glucose tolerance, type 1 diabetes, obesity, metabolic syndrome X, or dyslipidemia, diabetes during pregnancy, pre-diabetes, Alzheimer's disease, MODY 1, MODY 2 or MODY 3 diabetes, mood disorders, and psychiatric disorders.

Described are complexes comprising insulin. The complexes described herein comprise insulin or a macromolecule attached to a glucose-binding diboronate motif (B1), and a macromolecule or insulin attached to a diol (D1). Further disclosed are methods of correcting blood glucose levels in a subject in need thereof, the methods comprising administering a complex described herein or a pharmaceutical composition comprising a complex described herein to the subject in need thereof.

The invention relates to a composition, in particular solid, comprising a permeation enhancer, said permeation enhancer being an acylated aminoacid substituted on the amine function, also called AC-aa-NS, said composition comprising in particular a peptide or a protein, the AC-aa-NS compounds, their methods of preparation and their use in medicine.

The invention belongs to the field of drug delivery, and particularly relates to a glucose and ketone body dual-response long-acting insulin delivery system as well as a preparation method and application thereof. The glucose and ketone body dual-response long-acting insulin delivery system provided by the invention comprises a drug crystal, a polymer coating wrapping the drug crystal and a phenylboronic acid based cationic polymer modified in the polymer coating. The long-acting insulin can prolong the treatment time of the glucose-responsive insulin delivery carrier, meanwhile, the glucose-responsive insulin delivery carrier has a ketone body response behavior, ketoacidosis is inhibited, and the problems that an existing glucose-responsive insulin delivery carrier is short in treatment time, a ketone body-responsive insulin delivery carrier is difficult to construct and the like are solved.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a fusion protein with an Fc fragment, such as a toll-like receptor 3-Fc (TLR3-Fc). In some embodiments of the present disclosure, the target biomolecule is toll-like receptor 9-Fc (TLR9-Fc). In some embodiments of the present disclosure, the target biomolecule is deoxyribonuclease I-Fc (DNAse I-Fc). In some embodiments of the present disclosure, the target biomolecule is neural growth factor-Fc (NGF-Fc). In some embodiments of the present disclosure, the target biomolecule is insulin-Fc.

Provided are compositions and methods for treating diabetes in a canine or feline. A canine or feline insulin-serum albumin fusion protein is administered to a subject.

The present invention relates to a composition comprising: an insulin derivative comprising at least one arylboronic acid or arylboroxol; and methionine, and to the use of the composition in the treatment of diabetes mellitus, including type 1 diabetes mellitus and type 2 diabetes mellitus.

The present invention belongs to the technical field of insulin derivatives. Disclosed are a phenylboronic-acid-based insulin derivative, and a preparation method therefor and the use thereof. The provided phenylboronic-acid-based insulin derivative has a good glucose-responsive release function, wherein the phenylboronic acid group binds to a glycosyl protein to generate a phenylboronic acid ester bond, thereby generating an insulin and glycosyl protein complex in situ in blood. When the concentration of glucose in the blood is high, the glucose specifically cleaves the phenylboronic acid ester bond, thereby releasing the insulin. The provided phenylboronic-acid-based insulin derivative achieves stable and rapid glucose-responsive insulin release, which can steadily and persistently maintain the blood glucose of a diabetic subject within the normal range with almost no occurrence of hypoglycemia.

To provide dosing regimens of GLP-1 analogs for the treatment of fat, obese, overweight, nonalcoholic fatty liver disease (NAFLD), and / or nonalcoholic steatohepatitis (NASH).SOLUTION: Administering to the subject a first effective amount of one or more first active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs; A dosing regimen is provided, comprising: a first effective amount administered continuously, or intermittently at an interval between two consecutive administrations of six hours or less; and one or more second active ingredients selected from the group consisting of a second effective amount of GLP-I and a GLP-1 analog, administered to said subject once daily, twice daily, three times daily, or four times daily.SELECTED DRAWING: None

Disclosed in the present invention is an acylated insulin preparation, a pharmaceutical composition of an acylated insulin and a long-acting GLP-1 compound, and a medical use of the preparation and the pharmaceutical composition.