393results 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 β-eliminative linkers suitable for the conjugation of small molecule, peptide, and protein and compounds comprising the linkers.

Described herein are particles comprising a first compartment, a second compartment, and a compound of Formula (I), as well as compositions and methods of making and using the same. The particles may comprise a cell capable of expressing a therapeutic agent useful for the treatment of a disease, disorder, or condition described herein.

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 invention relates to the field of medicines, and particularly discloses a fusion protein with a GIP and GLP-1 dual receptor agonist function and application of the fusion protein. A specifically designed GLP-1 / GIP targeting polypeptide is fused with the N end of an IgG4 heavy chain constant region and the N end of a light chain constant region or the N end of Fc to obtain the GLP-1 / GIP targeting polypeptide. A research result shows that the fusion protein with the GIP and GLP-1 dual receptor agonist function has an obvious effect of reducing the weight of a mouse, the weight of the liver of the mouse is also reduced, the blood sugar of the mouse is also remarkably reduced, and the total cholesterol in serum is reduced to a certain extent. Therefore, the compound can be applied to medicines or products for slimming, reducing blood sugar and treating fatty liver.

The present invention provides an aggregate, a preparation method thereof, and an oral insulin formulation. Specifically, an aggregate formed by the assembly of a chalcogen heterocyclic compound and insulin is provided. The aggregate can be further prepared into an oral insulin formulation. The oral formulation can be used to lower the blood glucose level of mammals and is used as part of a diabetes treatment regimen. The chalcogen heterocyclic compound in the oral insulin formulation prepared by this method can effectively protect insulin from overcoming the three major physiological barriers of the oral intake route, is stable in the gastrointestinal environment, and undergoes a dynamic chemical exchange reaction with the sulfhydryl groups of intestinal mucin in intestinal fluid and the proteins on the inner and outer sides of the epithelial cell membrane through the surface poly-chalcogen molecular bond, entering the circulatory system from intestinal epithelial cells and playing a role in lowering blood glucose. When the oral insulin formulation is administered orally, it has high bioavailability and good blood glucose lowering effect in mammals and can be used for the treatment of diabetes.

Provided herein, inter alia, are methods and compositions for engineering T cells. The methods include culturing T cells with insulin during engineering of the T cells. The methods provided herein contemplate to increase cell viability, expansion and gene editing efficiency, allowing for an increase in the total number of engineered T cells.

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.

Disclosed herein are compositions that are useful for targeting a signaling pathway modulator to a muscle cell. In some instances, such compositions may be useful in treating a muscle disorder, such as muscular dystrophy.

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.

A two-chain insulin analogue contains a modified A-chain polypeptide and a modified B-chain polypeptide. The A-chain polypeptide comprises one or more of: a His or Glu substitution at position A8, a Glu substitution at position A14; and a Gln or Arg substitution at position A17. The B-chain polypeptide comprises one or more of: a deletion of the amino acids at position B1, B1-B2, B1-B3, B30 or a combination thereof; an Ala or Glu substitution at position B2; a Glu substitution at position B3. The analogue exhibits thermodynamic stability in a zinc-free solution, decreased self-association, maintains biological potency, and no increased mitogenicity. The analogue exhibits resistance to chemical degradation and physical degradation. A method of treating a patient with diabetes mellitus or obesity comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.

Disclosed is an acylated insulin, a pharmaceutical formulation thereof, a pharmaceutical composition thereof with a long-acting GLP-1 compound, and a medical use of the acylated insulin, the pharmaceutical formulation and the pharmaceutical composition. Compared with insulin degludec or other insulin derivatives, the acylated insulin has an unexpected, significantly increased drug effect, a longer duration of action, a longer in vivo half-life, an excellent bioavailability, as well as better physical and chemical stabilities.

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.

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.

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.

A synthetic organelle-assisted gene expression method, a DNA construct, an expression system, and use of a synthetic organelle. An efficient and feasible method eliminates the stress and / or toxicity of a gene expression product on a host, and provides a suitable and controllable maturation environment for the gene expression product, thus optimizing gene expression.

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).