B-chain Modified Insulin Patents (Class 514/6.3)
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Publication number: 20140057841Abstract: Disclosed is a recombinant human insulin or analog conjugate thereof. Said conjugate is formed by connecting the ?-amino group of lysine 29 of the B chain to activated polyethylene glycol by means of an amide bond. Further disclosed is a method of preparing said conjugate, a pharmaceutical compound, and a use for said conjugate in preparing medication for treating Type 1 and Type 2 diabetes.Type: ApplicationFiled: March 19, 2012Publication date: February 27, 2014Applicant: Chongqing Fagen Biomedical Inc.Inventors: Kai Fan, Yu Cao, Yong Chen, Hongliang Li, Hairong Chen, Ying Wan
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Publication number: 20140038888Abstract: The invention relates to a pharmaceutical composition comprising 1.a and/or 1.b according to claim 1 in combination with at least one second therapeutic agent 2 which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.Type: ApplicationFiled: October 8, 2013Publication date: February 6, 2014Applicant: Boehringer Ingelheim International GmbHInventors: Bradford S. HAMILTON, Thomas RAUCH, Manami TSUTSUMI
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Publication number: 20140031280Abstract: Methods for preventing and/or treating symptoms of Post-Traumatic Stress Disorder (PTSD) are provided. The preferred method comprises administration of an effective amount of insulin to the upper one-third of a mammal's, preferably a human, nasal cavity, thereby enabling the administered at least one effective amount of insulin to bypass the patient's blood-brain barrier and be directly delivered to the patient's CNS. Another embodiment comprises utilizing vasoconstrictors to enhance targeting of an effective amount of insulin to the CNS while reducing non-target exposure.Type: ApplicationFiled: September 30, 2013Publication date: January 30, 2014Applicant: HealthPartners Research & EducationInventor: William H. Frey, II
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Patent number: 8633156Abstract: The invention relates to novel insulin analogs having a basal time-action profile, which are characterized by the addition and/or substitution of negatively and positively charged amino acid residues and by an amidation of the C-terminal carboxy group of the B chain and histidine in position 8 of the insulin A chain. The invention also relates to the production and use thereof.Type: GrantFiled: June 22, 2010Date of Patent: January 21, 2014Assignee: Sanofi-Aventis Deutschland GmbHInventors: Paul Habermann, Gerhard Seipke, Roland Kurrle, Gunter Muller, Mark Sommerfeld, Norbert Tennagels, Georg Tschank, Ulrich Werner
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Publication number: 20130336952Abstract: The present disclosure relates to compositions and methods for accelerating the healing process of wounds, increasing the closure of skin wounds, and decreasing inflammation at the site of a skin wound. Specifically, the disclosure relates to compositions comprising a delta-PKC activator, an alpha-PKC inhibitor, and a pharmaceutically acceptable carrier that is free of Ca2+ and Mg2+ cations. The disclosure also relates to compositions comprising an insulin or insulin analog and a pharmaceutically acceptable carrier that is free of Ca2+ and Mg2+ cations.Type: ApplicationFiled: February 15, 2013Publication date: December 19, 2013Applicant: HEALOR LTD.Inventor: HealOr Ltd.
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Publication number: 20130331320Abstract: Insulin preparations comprising a long-acting insulin compound, a fast-acting insulin compound, a nicotinic compound and an amino acid.Type: ApplicationFiled: December 14, 2011Publication date: December 12, 2013Applicant: Novo Nordisk A/SInventors: Svend Havelund, Ulla Ribel-Madsen, Ib Jonassen, Helle Birk Olsen
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Patent number: 8603970Abstract: The invention relates to novel insulin analogs having a basal time-action profile, which are characterized by the addition and/or substitution of negatively and positively charged amino acid residues and by an amidation of the C-terminal carboxy group of the B chain and histidine in position 8 of the insulin A chain. The invention also relates to the production and use thereof.Type: GrantFiled: June 22, 2010Date of Patent: December 10, 2013Assignee: Sanofi-Aventis Deutschland GmbHInventors: Paul Habermann, Gerhard Seipke, Roland Kurrle, Gunter Muller, Mark Sommerfeld, Norbert Tennagels, Georg Tschank, Ulrich Werner
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Patent number: 8575096Abstract: The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.Type: GrantFiled: August 12, 2008Date of Patent: November 5, 2013Assignee: Novo Nordisk A/SInventors: Helle Birk Olsen, Thomas Børglum Kjeldsen, Per Balschmidt, Tine Glendorf, Svend Havelund
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Patent number: 8569231Abstract: In one aspect, the disclosure provides a conjugate comprising an insulin molecule having an A-chain and a B-chain; an affinity ligand covalently bound to the A-chain; and a monovalent glucose binding agent covalently bound to the B-chain, wherein the affinity ligand competes with glucose for non-covalent binding with the monovalent glucose binding agent. In the absence of glucose, the monovalent glucose binding agent binds the affinity ligand to produce a “closed” inactive form of the insulin molecule. When free glucose is added, it competes with the affinity ligand for binding with the monovalent glucose binding agent to produce an “open” active form of the insulin molecule. The monovalent glucose binding agent and affinity ligand are covalently bound to the insulin molecule. The disclosure also provides methods of using these conjugates and methods of making these conjugates. In another aspect, the disclosure provides exemplary conjugates.Type: GrantFiled: January 27, 2010Date of Patent: October 29, 2013Assignee: Smartcells, Inc.Inventors: Todd C. Zion, Thomas M. Lancaster
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Publication number: 20130281364Abstract: Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.Type: ApplicationFiled: November 7, 2012Publication date: October 24, 2013Applicant: NOVO NORDISK A/SInventor: Novo Nordisk A/S
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Publication number: 20130261051Abstract: The present invention relates to methods for treatment of a condition or disease where administration of insulin will be of benefit, comprising administering, to a patient in need thereof, effective dosages of an insulin, insulin analogue or derivative thereof, which exhibits a prolonged profile of action, wherein said dosages are administered at intervals of varying length.Type: ApplicationFiled: October 27, 2011Publication date: October 3, 2013Inventor: Thue Johansen
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Patent number: 8501440Abstract: 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.Type: GrantFiled: May 16, 2012Date of Patent: August 6, 2013Assignee: Case Western Reserve UniversityInventor: Michael Weiss
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Publication number: 20130196906Abstract: Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.Type: ApplicationFiled: January 29, 2013Publication date: August 1, 2013Applicant: CERULEAN PHARMA INC.Inventor: Cerulean Pharma Inc.
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Patent number: 8481485Abstract: Full potency analogs of insulin are provided wherein the analog comprises a modification of the tyrosine residue at position 19 of the A chain.Type: GrantFiled: December 18, 2009Date of Patent: July 9, 2013Assignee: Indiana University Research and Technology CorporationInventors: Richard D. DiMarchi, Jie Han
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Patent number: 8476228Abstract: The present invention relates to insulin derivatives having a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.Type: GrantFiled: October 14, 2011Date of Patent: July 2, 2013Assignee: Novo Nordisk A/SInventors: János Tibor Kodra, Patrick William Garibay, Thomas Hoeg-Jensen, Ib Jonassen, Peter Madsen, Tina Møller Tagmose
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Publication number: 20130143803Abstract: The invention concerns a process for preparing a pharmaceutical formulation comprising an insulin derivative, wherein the process comprises dissolving an insulin derivative in water, adjusting the pH of the solution to a pH above 7.2, adding a zinc solution while stirring continuously and adjusting the pH to the target pH of the formulation.Type: ApplicationFiled: May 9, 2011Publication date: June 6, 2013Applicant: NOVO NORDISK A/SInventors: Lene Andresen, Rosa Rebecca Erritzoee Hansen, Per Jeppesen
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Publication number: 20130085099Abstract: The present invention provides therapeutic agents and compositions comprising elastin-like peptides (ELPs) and therapeutic proteins. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist, insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistence in the body, solubility, and bioavailability.Type: ApplicationFiled: June 15, 2012Publication date: April 4, 2013Applicant: DUKE UNIVERSITYInventor: Ashutosh Chilkoti
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Patent number: 8410048Abstract: The invention relates to a method for producing a type of insulin by genetically engineering a precursor thereof and converting said precursor to the respective insulin in an enzyme-catalyzed ligation reaction with lysine amide or arginine amide, or by lysine or arginine which is modified by protective groups, and optionally subsequent hydrolysis.Type: GrantFiled: January 7, 2009Date of Patent: April 2, 2013Assignee: Sanofi-Aventis Deutschland GmbHInventors: Paul Habermann, Frank Zocher
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Publication number: 20130065826Abstract: A composition in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, includes at least a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and a dextran substituted by radicals carrying carboxylate charges and hydrophobic radicals. Single-dose formulations at a pH of between 7 and 7.8 includes a basal insulin whose isoelectric point is between 5.8 and 8.5 and a prandial insulin.Type: ApplicationFiled: August 9, 2012Publication date: March 14, 2013Applicant: ADOCIAInventors: Olivier SOULA, Gérard SOULA, Jeff TONNAR
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Patent number: 8343914Abstract: Protection of proteins against fibrillation may be afforded by introduction of certain histidine substitutions into the protein, such that a pair of histidines are present with sufficient spacing as to allow the histidines to coordinate with zinc. In the case of insulin, introduction of histidine residue substitutions at residues A4 and A8 together or a histidine residue substitution at residue B1, provides increased resistance to fibrillation while maintaining at least a majority of the activity of the insulin analogue. Introduction of a histidine residue substitution at residue A8 restores at least a portion of fibrillation resistance that may have been harmed by substitutions present on the B-chain such as those present in fast-acting insulins. Proteins protected by such histidine substitutions may be used to provide a pharmaceutical composition. A method of treating a patient includes administering a physiologically effective amount of the pharmaceutical composition to the patient.Type: GrantFiled: January 8, 2007Date of Patent: January 1, 2013Assignee: Case Western Reserve UniversityInventor: Michael Weiss
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Patent number: 8324157Abstract: Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.Type: GrantFiled: December 1, 2011Date of Patent: December 4, 2012Assignee: Novo Nordisk A/SInventors: Helle Birk Olsen, Svend Havelund, Ulla Ribel-Madsen, Jeppe Sturis, Helle Naver, Morten Schlein, Svend Ludvigsen
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Publication number: 20120277149Abstract: The invention relates to a pharmaceutical composition comprising 1.a and/or 1.b according to claim 1 in combination with at least one second therapeutic agent 2 which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.Type: ApplicationFiled: October 31, 2011Publication date: November 1, 2012Applicant: BOEHRINGER INGELHEIM INTERNATIONAL GMBHInventors: Bradford S. Hamilton, Thomas Rauch, Manami Tsutsumi
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Publication number: 20120252724Abstract: The invention relates to an aqueous pharmaceutical formulation having insulin, an insulin analog, or an insulin derivative, and methionine; and to the production thereof, to the use thereof for treating diabetes mellitus, and to a medication for treating diabetes mellitus.Type: ApplicationFiled: July 2, 2010Publication date: October 4, 2012Applicant: SANOFI-AVENTISInventors: Isabell Schoettle, Annika Hagendorf, Christiane Fuerst, Gerrit Hauck, Verena Siefke-Henzler, Walter Kamm, Julia Schnieders
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Publication number: 20120208749Abstract: The present invention is related to insulin derivatives having a side chain attached either to the ?-amino group of the N-terminal amino acid residue of B chain or to an ?-amino group of a Lys residue present in the B chain of the parent insulin molecule via an amide bond which side chain comprises one or more residues of ethyleneglycol, propyleneglycol and/or butyleneglycol containing independently at each termini a group selected from —NH2 and —COOH; a fatty diacid moiety with 4 to 22 carbon atoms, at least one free carboxylic acid group or a group which is negatively charged at neutral pH; and possible linkers which link the individual components in the side chain together via amide or ether bonds, said linkers optionally comprising a free carboxylic acid group.Type: ApplicationFiled: April 9, 2012Publication date: August 16, 2012Applicant: Novo Nordisk A/SInventors: Patrick William Garibay, Thomas Hoeg-Jensen, Ib Jonassen, Svend Havelund, Peter Madsen, Palle Jakobsen
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Publication number: 20120183616Abstract: The present invention relates to a pharmaceutical composition comprising an insulin compound in a concentration that is sufficient to maintain a therapeutically effective level of the insulin compound in blood plasma for at least 3 days characterized by having a pharmacokinetic profile in vivo with substantially no burst of the insulin compound. The present invention further relates to the use of an insulin compound for preparing said pharmaceutical composition as well as a kit of parts comprising said pharmaceutical composition.Type: ApplicationFiled: July 30, 2010Publication date: July 19, 2012Applicant: SANOFI-AVENTIS DEUTSCHLAND GMBHInventors: Kennett Sprogoe, Felix Cleemann, Ulrich Hersel, Silvia Kaden-Vagt, Torben Lessmann, Harald Rau, Thomas Wegge
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Publication number: 20120184487Abstract: The novel insulin derivates delivers, after administration to humans, insulin as a function of the glucose concentration in the tissue.Type: ApplicationFiled: June 29, 2010Publication date: July 19, 2012Applicant: Novo Nordisk A/SInventors: Thomas Hoeg-Jensen, Palle Jakobsen, Ulrich Sensfuss, Christian Fledelius, Ulla Ribel-Madsen
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Publication number: 20120165251Abstract: The present invention relates to methods for treating and/or preventing metabolic diseases comprising the combined administration of a DPP-4 inhibitor and a long-acting insulin. The invention further relates to a DPP-4 inhibitor for subcutaneous or transdermal use.Type: ApplicationFiled: June 23, 2011Publication date: June 28, 2012Applicant: BOEHRINGER INGELHEIM INTERNATIONAL GMBHInventors: Thomas KLEIN, Michael MARK, Leo THOMAS
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Patent number: 8192957Abstract: 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.Type: GrantFiled: April 6, 2009Date of Patent: June 5, 2012Assignee: Case Western Reserve UniversityInventor: Michael Weiss
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Publication number: 20120135920Abstract: Insulin preparations comprising an insulin compound or a mixture of two or more insulin compounds, a nicotinic compound and an amino acid.Type: ApplicationFiled: December 1, 2011Publication date: May 31, 2012Applicant: Novo Nordisk A/SInventors: Helle Birk Olsen, Svend Havelund, Ulla Ribel-Madsen, Jeppe Sturis, Helle Naver, Morten Schlein, Svend Ludvigsen
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Publication number: 20120122775Abstract: Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.Type: ApplicationFiled: January 25, 2012Publication date: May 17, 2012Applicant: MANNKIND CORPORATIONInventors: Anders Hasager Boss, Richard Petrucci, Campbell Howard, Alfred Mann
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Publication number: 20120094903Abstract: What is described is a pharmaceutical formulation for intranasal delivery of insulin to a patient, comprising an aqueous mixture of human insulin, a solubilizing agent, a surface active agent, and a thickening agent, wherein said formulation provides a ultra-rapid acting profile to regular human insulin.Type: ApplicationFiled: December 7, 2011Publication date: April 19, 2012Applicant: MARINA BIOTECH INC.Inventors: Henry R. Costantino, Annemarie Stoudt Cohen, Anthony P. Sileno
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Patent number: 8158583Abstract: Pharmaceutical composition for parenteral administration comprising a meal related insulin peptide and an insulinotropic peptide.Type: GrantFiled: May 12, 2009Date of Patent: April 17, 2012Assignee: Novo Nordisk A/SInventors: Liselotte Bjerre Knudsen, Kristian Tage Hansen, Dorthe Kot Engelund, Svend Ludvigsen, Lars Hansen, Claude Bonde, Ejvind Jensen, Tine Elisabeth Gottschalk Bøving, Morten Schlein
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Publication number: 20120071402Abstract: Novel PEGylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H. The PEGylation is at B29K.Type: ApplicationFiled: November 29, 2011Publication date: March 22, 2012Applicant: Novo Nordisk A/SInventors: Peter Madsen, Thomas Hoeg-Jensen, Thomas Børglum Kjeldsen, Tina Møller Tagmose
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Publication number: 20120035103Abstract: The present invention provides pharmaceutical compositions including alkylglycosides admixed with at least one of fast-acting and long-acting insulin analogs for treatment of disorders, such as diabetes.Type: ApplicationFiled: January 28, 2011Publication date: February 9, 2012Inventors: Dennis J. Pillion, Elias Meezan
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Publication number: 20120035104Abstract: The present invention relates to insulin derivatives having a side chain attached either to the ?-amino group of the N-terminal amino acid residue of the B chain or to the ?-amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.Type: ApplicationFiled: October 14, 2011Publication date: February 9, 2012Applicant: Novo Nordisk A/SInventors: Janos Tibor Kodra, Patrick William Garibay, Thomas Hoeg-Jensen, Ib Jonassen, Peter Madsen, Tina Moeller Tagmose
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Publication number: 20120021978Abstract: The invention relates to a drug comprising at least one insulin and at least one GLP-1 receptor agonist.Type: ApplicationFiled: October 9, 2009Publication date: January 26, 2012Applicant: SANOFI-AVENTIS DEUTSCHLAND GMBHInventors: Ulrich Werner, Barbel Rotthauser, Christopher James Smith
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Patent number: 8067362Abstract: The present invention relates to insulin derivatives having a side chain attached either to the -amino group of the N-terminal amino acid residue of the B chain or to the amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.Type: GrantFiled: February 1, 2006Date of Patent: November 29, 2011Assignee: Novo Nordisk ASInventors: János Tibor Kodra, Patrick William Garibay, Thomas Hoeg-Jensen, Tina Tagmose
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Publication number: 20110288013Abstract: This invention relates to methods of reducing risk of developing cardiovascular complications in diabetic patients. Specifically, the invention relates to the use of haptoglobin genotyping for determining the importance of maintaining tight glycemic control in diabetic subjects expressing Hp 2-2 allele.Type: ApplicationFiled: August 4, 2011Publication date: November 24, 2011Inventor: Andrew LEVY
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Patent number: 8058391Abstract: The invention claims a process for making an insulin-oligomer conjugate IN-105. IN-105 precursor having formula G-A-V-R-[B-Chain]-R-D-A-D-D-R-[A-Chain] is cloned and expressed in Pichia. The biosynthetic precursor is then conjugated with an activated oligomer. The IN-105 precursor-oligomer conjugate is then treated with protease and purified to afford active insulin-oligomer conjugate of formula insulin-OC—CH2—CH2—(OCH2CH2)3—OCH3.Type: GrantFiled: October 13, 2005Date of Patent: November 15, 2011Assignee: Biocon LimitedInventors: Nitesh Dave, Partha Hazra, Anuj Goel, Nita Roy, Anand Khedkar, Harish Iyer, Gautam Krishnan, H. S. Manjunath, Shrikumar Suryanarayan, Govindasamy Manikam, Goldy Sachdev, Mayank Garg
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Patent number: 8048854Abstract: The invention relates to insulin glargine which is modified by amidation, especially Gly(A21), Arg(B31), Arg amide (B32) human insulin (insulin glargine amide).Type: GrantFiled: January 7, 2009Date of Patent: November 1, 2011Assignee: Sanofi-Aventis Deutschland GmbHInventors: Paul Habermann, Frank Zocher
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Publication number: 20110230402Abstract: The present invention relates to an insulin derivative for the treatment of a condition or disease where administration of insulin will be of benefit, comprising administering, to a patient in need thereof, effective dosages of the insulin derivative, wherein said insulin derivative exhibits a prolonged profile of action and wherein said dosages are administered at intervals longer than 24 hours.Type: ApplicationFiled: October 29, 2009Publication date: September 22, 2011Applicant: Novo Nordisk A/SInventors: Thue Johansen, Birgitte Koch Michelsen, Berit Edsberg
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Publication number: 20110166064Abstract: An insulin analogue comprises a B-chain polypeptide incorporating a halogenated phenylalanine at position B24, B25 or B26. The halogenated phenylalanine may be ortho-monofluoro-phenylalanine, ortho-monobromo-phenylalanine, ortho-monochloro-phenylalanine, or para-monochloro-phenylalanine. The analogue may be of a mammalian insulin, such as human insulin. A nucleic acid encodes such an insulin analogue. The halogenated insulin analogues retain significant activity. A method of treating a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. Halogen substitution-based stabilization of insulin may enhance the treatment of diabetes mellitus in regions of the developing world lacking refrigeration.Type: ApplicationFiled: January 31, 2011Publication date: July 7, 2011Applicant: CASE WESTERN RESERVE UNIVERSITYInventor: Michael WEISS
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Publication number: 20110144010Abstract: The present invention relates to a solid or semi-solid pharmaceutical composition that includes a polypeptide drug, at least one polar organic solvent, at least one surfactant, at least one hydrophilic component and which composition is spontaneously dispersible.Type: ApplicationFiled: May 30, 2008Publication date: June 16, 2011Applicant: Novo Nordisk A/SInventors: Florian Anders Föger, Per-Olof Wahlund, Tomas Landh, Simon Bjerregaard Jensen, Svend Havelund
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Publication number: 20110124553Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y—PAG-Z—R2??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.Type: ApplicationFiled: January 18, 2011Publication date: May 26, 2011Inventors: Balasingam Radhakrishnan, Diti Aggarwal, Michelle Ferro, Kenneth D. James, Navdeep B. Malkar, Mark A. Miller, Monica Puskas, Nnochiri N. Ekwuribe
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Publication number: 20110105392Abstract: The present invention relates to the field of diabetes. More particularly, the invention relates to PEGylated insulin lispro compounds that are PEGylated with high molecular weight poly(ethylene glycol), are highly soluble at physiological pH, have an extended duration of action, and characterized by pharmacokinetic, pharmacodynamic, and/or activity peak-trough ratios of less than 2. The invention also relates to methods of providing such molecules, to pharmaceutical compositions containing them, and to their therapeutic uses.Type: ApplicationFiled: June 9, 2009Publication date: May 5, 2011Applicant: ELI LILLY AND COMPANYInventors: John Michael Beals, Gordon Butler Cutler, JR., Brandon Lee Doyle, Ryan John Hansen, Shun Li, Shahriar Shirani, Lianshan Zhang
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Publication number: 20110077196Abstract: An insulin analogue comprises a B-chain polypeptide containing at least one alteration selected from a methylated phenylalanine substitution at position B24 and an addition of two amino acids to the carboxyl end of the B-chain polypeptide. A first amino acid at position B31 is selected from glutamate and aspartate, and a second amino acid at position B32 is selected from glutamate, alanine and aspartate. The methylated phenylalanine may be ortho-monofluoro-phenylalanine, meta-monobromo-phenylalanine or para-monochloro-phenylalanine. The analogue may be an analogue of a mammalian insulin, such as human insulin. A nucleic acid encoding such an insulin analogue is also provided. A method of treating a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.Type: ApplicationFiled: September 17, 2010Publication date: March 31, 2011Applicant: CASE WESTERN RESERVE UNIVERSITYInventor: Michael A. Weiss
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Publication number: 20110021423Abstract: The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.Type: ApplicationFiled: August 12, 2008Publication date: January 27, 2011Applicant: NOVO NORIDSK A/SInventors: Helle Birk Olsen, Thomas Børglum Kjeldsen, Per Balschmidt, Tine Glendorf, Svend Havelund
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Publication number: 20100310542Abstract: The present disclosure relates to compositions and methods for accelerating the healing process of wounds, increasing the closure of skin wounds, and decreasing inflammation at the site of a skin wound. Specifically, the disclosure relates to compositions comprising a delta-PKC activator, an alpha-PKC inhibitor, and a pharmaceutically acceptable carrier that is free of Ca2+ and Mg2+ cations.Type: ApplicationFiled: July 30, 2008Publication date: December 9, 2010Applicant: HEALOR LTD.Inventors: Tamar Tennenbaum, Liora Braiman-Wiksman, Inessa Solomonik, Ofra Levy-Hacham, Ephraim Brener