35 results about "Insulin B Chain" patented technology

A fibrillation-resistant insulin analogue may be a single-chain insulin analogue or a physiologically acceptable salt thereof, containing an insulin A chain sequence or an analogue thereof and an insulin B chain sequence or an analogue thereof connected by a polypeptide of 4-10 amino acids. The fibrillation-resistant insulin analogue preferably displays less than 1 percent fibrillation with incubation at 37° C. for at least 21 days. A single-chain insulin analogue displays greater in vitro insulin receptor binding than normal insulin while displaying less than or equal binding to IGFR than normal insulin. The fibrillation-resistant insulin may be used to treat a patient using an implantable or external insulin pump, due to its greater fibrillation resistance.

The invention aims to provide a novel alkaline protease having peculiar properties such as high alkali activity, resistance to surfactants and calcium-dependent thermostability and exhibiting excellent performance in highly alkaline detergents, and a gene coding for the amino acid sequence thereof. There is provided an alkaline protease with such properties that an active pH range is from 5 to 13, an optimum pH is approximately 12.6, an optimum temperature is 70° C., no activity drop by heating is observed up to 65° C. at pH 10 and the optimum temperature and the thermostability are not affected by Ca2+ ions. Specifically, there is provided, for example, an alkaline protease having an amino acid sequence constituting a mature enzyme as represented by SEQ ID NO: 3 or an amino acid sequence resulting from deletion, substitution, situs inversus arrangement, addition or insertion of a part of amino acids thereof, or derived from Alkaliphillus transvaalensis. The protease cleaves 26 peptide bonds among 29 peptide bonds of acidic insulin B-chain.

A method treating a patient includes administering a physiologically effective amount of a fibrillation-resistant insulin analogue or a physiologically acceptable salt thereof to the patient. The fibrillation-resistant insulin analogue or a physiologically acceptable salt thereof, contains an insulin A-chain sequence modified at position A8 and an insulin B-chain sequence or an analogue thereof. The fibrillation-resistant insulin analogue may exhibit thermodynamic stability similar to or exceeding that of wild-type human insulin and displays a susceptibility to fibrillation similar to or exceeding that of wild-type human insulin. An insulin analogue may display greater in vitro insulin receptor binding than normal insulin while displaying binding to IGFR less than twice that of normal insulin and less than that of fast-acting insulin analogs. The fibrillation-resistant insulin may be used to treat a patient by subcutaneous injection or by using an implantable or external insulin pump, due to its fibrillation resistance.

The present invention provides new insulin strand B, monomeric insulin containing strand B, medicinal composition containing the monomeric insulin and their preparation process and use. The insulin analog B27K-DTrI sample of high purity is obtained via enzymatic semi-synthesis process and is proved to have the property of monomeric insulin and overall insulin activity 80 % of that of normal insulin. The monomeric insulin precursor is secreted and expressed in yeast expressing system and enzyme cut to obtain B27K-DTrI, and the enzymatic peptide converting step is omitted to raise the final yield and suit for industrial production.

Methods are described for determining the amount of insulin in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying insulin in a biological sample utilizing purification methods coupled with tandem mass spectrometric or high resolution / high accuracy mass spectrometric techniques.

The invention features methods for the prevention or treatment of autoimmune disorders in humans. The methods include administering an autoantigen in combination with an oil-based carrier. Included are methods for the prevention and treatment of diabetes mellitus which include treating a patient with a diabetes type 1 autoantigen, e.g., human insulin B-chain or GAD65, and an oil-based carrier approved for human use. Also included are vaccines and kits for the treatment of diabetes mellitus.

A pharmaceutical formulation comprises insulin having a variant insulin B-chain polypeptide containing an ortho-monofluoro-Phenylalanine substitution at position B24 in combination with a substitution of an amino acid containing an acidic side chain at position B10, allowing the insulin to be present at a concentration of between 0.6 mM and 3.0 mM. The formulation may optionally be devoid of zinc. Amino-acid substitutions at one or more of positions B3, B28, and B29 may additionally be present. The variant B-chain polypeptide may be a portion of a proinsulin analog or single-chain insulin analog. The insulin analog may be an analog of a mammalian insulin, such as human insulin. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analog or a physiologically acceptable salt thereof to the patient.

An insulin analogue comprises an insulin B-chain polypeptide modified with an O-linked monosaccaride pyranoside adduct at the side chain of residue B27 or an O-linked monosaccaride pyranoside adduct at the side chain of residue B30, or both, where the positions are recited relative to human insulin. The monosaccaride may be a manopyranoside, an N-acetyl-galactopyranoside, or a glucopyranoside. The insulin analogue may additionally comprise containing a foreshortened B-chain polypeptide lacking residues B1-B3, an extension of 1 or 2 Glu residues on the carboxy terminal end of the B-chain polypeptide, an extension of ornithine at the carboxy-terminal end of the B-chain, the substitutions Lys at position B28 and Pro at position B29, an ornithine substitution at position B29, or combinations thereof. The analogue may be an analogue of a mammalian insulin, such as human insulin. A method of treating a patient comprises administering a physiologically effective amount of the insulin analogue.

The present invention is directed toward peptide analogues of insulin B chain that are generally derived from peptides comprising residues 9 to 23 of the native B chain sequence. The analogues are altered from the native sequence at position 12, 13, 15 and / or 16, and may be additionally be altered at position 19 and / or other positions. Pharmaceutical compositions containing these peptide analogues are provided. The peptide analogues are useful for treating and inhibiting the development of diabetes.

The invention discloses a new insuline B chain, monomer quick-effective insuline and medicinal composite. This invention also relates to preparing method and usage.

The present invention provides new insulin strand B, monomeric insulin containing strand B, medicinal composition containing the monomeric insulin and their preparation process and use. The insulin analog B27K-DTrI sample of high purity is obtained via enzymatic semi-synthesis process and is proved to have the property of monomeric insulin and overall insulin activity 80 % of that of normal insulin. The monomeric insulin precursor is secreted and expressed in yeast expressing system and enzyme cut to obtain B27K-DTrI, and the enzymatic peptide converting step is omitted to raise the final yield and suit for industrial production.

The invention discloses an insulin B chain HLA-A*0201 restrictive CTL epitope altered peptide ligand (APL) and an acquisition method and application thereof. The amino acid sequence of the APL is HLCGPFLVEA, and is obtained by replacing the sixth position histidine of the natural epitope mInsB5-14 by phenylalanine. The acquisition method comprises the following steps of: establishing a TCR-HLA-A*0201-mInsB5-14 compound model, determining potential TCR acting loci in the mInsB5-14, performing monoamino acid mutation on the potential TCR acting loci, and screening candidate APL having higher affinity with the HLA-A*0201 molecules than the natural epitope and space conformation close to the natural epitope; and further identifying the APL capable of obviously reducing mInsB5-14 specificity CTL response level through cell function experiments. The APL of the invention can be used for preparing a type 1 diabetes treatment negative peptide vaccine.