Insulin; Related Peptides Patents (Class 530/303)
-
Patent number: 8946148Abstract: Modified insulin polypeptides and their uses thereof are provided.Type: GrantFiled: November 20, 2008Date of Patent: February 3, 2015Assignee: Ambrx, Inc.Inventors: Zhenwei Miao, Denise Krawitz, Vadim Kraynov, Feng Tian, Bee-Cheng Sim, Lillian Skidmore, Anna-Maria A. Hays Putnam, Nick Knudsen, Michael Deguzman
-
Publication number: 20150031609Abstract: Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.Type: ApplicationFiled: October 13, 2014Publication date: January 29, 2015Inventors: Solomon S. Steiner, Rodney J. Woods, Joseph W. Sulner
-
Patent number: 8940860Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.Type: GrantFiled: June 16, 2011Date of Patent: January 27, 2015Assignee: Indiana University Research and Technology CorporationInventors: Richard D. DiMarchi, Julia Azriel, Zach Kaur, Jonathan Meyers, Todd Parody, Yan Zhao
-
Publication number: 20150024455Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.Type: ApplicationFiled: July 17, 2014Publication date: January 22, 2015Inventors: Juergen Siekmann, Stefan Haider, Hanspeter Rottensteiner, Peter Turecek
-
Publication number: 20150017699Abstract: The present invention is generally directed to internally functionalized graphene substrates, methods of making such substrates and methods of using such substrates. In one aspect, the present invention is a graphene substrate. The substrate comprises edge and non-edge regions. Organic or inorganic molecules are bound to the non-edge regions of the substrate, and the organic or inorganic molecules are present on the substrate edges at a population greater than about one molecule per 10,000 nm2.Type: ApplicationFiled: July 9, 2014Publication date: January 15, 2015Applicant: NANOTECH BIOMACHINES, INC.Inventors: Jeffrey Alan McKinney, William Emerson Martinez
-
Patent number: 8933207Abstract: The present invention relates to methods for synthesizing compounds of formula I or pharmaceutically acceptable salts thereof: I wherein each of X, Alk1, Alk2, and W are as defined and described herein.Type: GrantFiled: July 22, 2011Date of Patent: January 13, 2015Assignee: SmartCells, Inc.Inventors: Zhiyu Chen, Thomas M. Lancaster, Todd C. Zion
-
Publication number: 20150010494Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidised polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.Type: ApplicationFiled: September 22, 2014Publication date: January 8, 2015Inventors: Gord Adamson, David Bell, Steven Brookes
-
Patent number: 8927489Abstract: The present invention provides a pharmaceutical composition for the sustained release of C-peptide. The composition is in the form of a gel containing C-peptide. The gel formation is achieved by the adjustment of pH of the composition and/or by addition of divalent metal ions. The composition does not include any other gel-forming agents. Methods for producing the composition, medical uses of the composition and products containing two or more gel compositions as a combined preparation are also encompassed.Type: GrantFiled: June 2, 2006Date of Patent: January 6, 2015Assignee: Cebix IncorporatedInventors: John Wahren, Anders Carlsson
-
Publication number: 20150005231Abstract: 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: September 3, 2014Publication date: January 1, 2015Inventor: Michael WEISS
-
Publication number: 20140371140Abstract: The present invention is related to insulin derivatives containing additional disulfide bonds and methods of making such.Type: ApplicationFiled: August 28, 2014Publication date: December 18, 2014Inventors: Peter Madsen, Frantisek Hubalek, Thomas Boerglum Kjeldsen, Svend Ludvigsen
-
Publication number: 20140357838Abstract: The invention is related to novel N-terminally modified insulin derivatives comprising extra disulphide bond(s), pharmaceutical compositions comprising such and methods of making such.Type: ApplicationFiled: December 21, 2012Publication date: December 4, 2014Applicant: NOVO NORDISK A/SInventors: Peter Madsen, Thomas B. Kjeldsen, Tina M. Tagmose
-
Patent number: 8901484Abstract: The present invention relates to a method for the quantitative determination of an impurity present in a peptide product, wherein the impurity cannot be separated from other impurities or the main product. The method particularly involves the use of high resolution mass spectrometry (MS) detection with or without high performance liquid chromatography (HPLC). The method can be used for the investigation of the quality of peptides and proteins, particularly of pharmaceutical peptides and proteins.Type: GrantFiled: April 25, 2013Date of Patent: December 2, 2014Assignee: Sanofi-Aventis Deutschland GmbHInventors: Martin Vogel, Werner Mueller
-
Publication number: 20140349925Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have 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, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.Type: ApplicationFiled: August 6, 2014Publication date: November 27, 2014Inventors: Ib Jonassen, Thomas Hoeg-Jensen, Svend Havelund, Ulla Ribel-Madsen, Tina Moeller Tagmose, Peter Madsen
-
Patent number: 8889099Abstract: Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and/or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.Type: GrantFiled: January 30, 2013Date of Patent: November 18, 2014Assignee: MannKind CorporationInventors: Solomon S. Steiner, Rodney J. Woods, Joseph W. Sulner
-
Patent number: 8883722Abstract: The present invention is related to human insulin containing additional disulfide bonds and methods of making such.Type: GrantFiled: June 21, 2011Date of Patent: November 11, 2014Assignee: Novo Nordisk A/SInventors: Frantisek Hubalek, Tine Nygaard Vinther, Thomas Boerglum Kjeldsen, Svend Ludvigsen
-
Patent number: 8883449Abstract: The present invention is related to single-chain insulin having insulin activity comprising a B- and an A-chain or a modified B- and A-chain connected by a connecting peptide of from 6-11 amino acids. The single-chain insulins will have biological insulin activity and an IGF-1 receptor affinity similar to or lower than that of human insulin and a high physical stability. The single-chain insulin may contain at least one basic amino acid residues in the connecting peptide. The single-chain insulins may also be acylated in one or more Lys residues.Type: GrantFiled: October 15, 2008Date of Patent: November 11, 2014Assignee: Novo Nordisk A/SInventors: Thomas Børglum Kjeldsen, Morten Schlein, Anders Robert Sørensen, Peter Madsen
-
Publication number: 20140328900Abstract: A process for preparing human relaxin-2 having the following amino acid sequence: A chain: (SEQ?ID?NO:?1) pGlu-Leu-Tyr-Ser-Ala-Leu-Ala-Asn-Lys-Cys-Cys-His- Val-Gly-Cys-Thr-Lys-Arg-Ser-Leu-Ala-Arg-Phe-Cys B chain: (SEQ?ID?NO:?2) Asp-Ser-Trp-Met-Glu-Glu-Val-Ile-Lys-Leu-Cys-Gly- Arg-Glu-Leu-Val-Arg-Ala-Gln-Ile-Ala-Ile-Cys-Gly- Met-Ser-Thr-Trp-Ser; comprising the following steps: providing the amino acids necessary for the synthesis of the A and B chains with usual protective groups, wherein the cysteines are employed as trityl-protected amino acids (L-Cys(Trt)-OH); effecting a chromatographic purification of the individual chains A and B after the solid state synthesis; followed by the simultaneous folding and combination of the individual chains A and B in ammonium hydrogencarbonate buffer at pH 7.9 to 8.4; and subsequent purification of the relaxin-2 formed.Type: ApplicationFiled: August 3, 2012Publication date: November 6, 2014Applicant: PHARIS BIOTEC GMBHInventors: Wolf-Georg Forssmann, Thomas Dschietzig, Ludger Ständker, Andreas Zgraja, Jochen Hirsch
-
Publication number: 20140323398Abstract: 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 analogue or single-chain insulin analogue. The insulin analogue may be an analogue 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 analogue or a physiologically acceptable salt thereof to the patient.Type: ApplicationFiled: October 29, 2012Publication date: October 30, 2014Inventor: Michael A. Weiss
-
Publication number: 20140315798Abstract: The subject matter of this invention is directed towards chemically and thermodynamically stable single-chain insulin (SCI) analogues that are resistant to deamidation and fibrillation. The invention further discloses improved methods for the recombinant expression, purification and refolding of SCI.Type: ApplicationFiled: April 16, 2014Publication date: October 23, 2014Applicant: AMIDEBIO LLCInventors: Michael H.B. Stowell, Yanyu Peng, Mikhail Plam
-
Publication number: 20140315797Abstract: The invention is related to novel N-terminally modified insulin derivatives, pharmaceutical compositions comprising such and methods of making such.Type: ApplicationFiled: October 14, 2011Publication date: October 23, 2014Inventors: Peter Madsen, Per Balschmidt, Svend Havelund, Thomas Hoeg-Jensen, Thomas Boerglum Kjeldsen, Charlotte Harkjaer Fynbo
-
Publication number: 20140303076Abstract: An insulin analogue comprises a B-chain polypeptide containing a cyclohexanylalanine substitution at position B24 and optionally containing additional amino-acid substitutions at positions A8, B28, and/or B29. A proinsulin analogue or single-chain insulin analogue containing a B domain containing a cyclohexanylalanine substitution at position B24 and optionally containing additional amino-acid substitutions at positions A8, B28, and/or B29. 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 lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. A method of semi-synthesis using an unprotected octapeptide by means of modification of an endogenous tryptic site by non-standard amino-acid substitutions.Type: ApplicationFiled: July 13, 2012Publication date: October 9, 2014Applicant: CASE WESTERN RESERVE UNIVERSITYInventor: Michael A. Weiss
-
Publication number: 20140296475Abstract: A method for preparing a conjugate of a physiologically active polypeptide and a non-peptide polymer by linking physiologically active polypeptide with non-peptide polymer through a covalent bond using an organic solvent is provided. A method for preparing a physiologically active polypeptide complex by linking the conjugate with a carrier is provided. The complex shows improved in vivo duration and stability of the physiologically active polypeptide. The method can prepare the conjugate at a lower production cost, and the resulting conjugate shows an extension of in vivo activity at a relatively high level and significantly increase in the blood half-life.Type: ApplicationFiled: November 2, 2012Publication date: October 2, 2014Applicant: HANMI SCIENCE CO., LTDInventors: Dae Jin Kim, Myung Hyun Jang, Seung Su Kim, Jong Soo Lee, Jae Hyuk Choi, Se Chang Kwon
-
Publication number: 20140275476Abstract: The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.Type: ApplicationFiled: May 19, 2014Publication date: September 18, 2014Applicant: SmartCells, Inc.Inventors: Thomas M. Lancaster, Todd C. Zion
-
Publication number: 20140274888Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.Type: ApplicationFiled: May 30, 2014Publication date: September 18, 2014Applicant: SmartCells, Inc.Inventors: Todd C. Zion, Thomas M. Lancaster
-
Publication number: 20140255991Abstract: Methods for producing modified polypeptides containing amino acid analogues are disclosed. The invention further provides purified dihydrofolate reductase polypeptides, produced by the methods of the invention, in which the methionine residues have been replaced with homoallylglycine, homoproparglycine, norvaline, norleucine, cis-crotylglycine, trans-crotylglycine, 2-aminoheptanoic acid, 2-butynylglycine and allylglycine.Type: ApplicationFiled: January 9, 2014Publication date: September 11, 2014Applicant: California Institute of TechnologyInventors: David A. Tirrell, Kristi Lynn Kiick
-
Patent number: 8828923Abstract: The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have 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, the side chain being of the general formula: —W—X—Y—Z wherein W, X, Y and Z are as defined in the disclosure.Type: GrantFiled: September 16, 2009Date of Patent: September 9, 2014Assignee: Novo Nordisk A/SInventors: Ib Jonassen, Thomas Hoeg-Jensen, Svend Havelund, Ulla Ribel-Madsen, Tina Møller Tagmose, Peter Madsen
-
Patent number: 8815798Abstract: The present invention is related to insulin analogs containing additional disulfide bonds and methods of making such.Type: GrantFiled: June 21, 2011Date of Patent: August 26, 2014Assignee: Novo Nordisk A/SInventors: Svend Ludvigsen, Frantisek Hubalek, Thomas B. Kjeldsen, Tine N. Vinther
-
Patent number: 8809501Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.Type: GrantFiled: June 4, 2012Date of Patent: August 19, 2014Assignees: Baxter International Inc., Baxter Healthcare SAInventors: Juergen Siekmann, Stefan Haider, Hanspeter Rottensteiner, Peter Turecek
-
Patent number: 8809269Abstract: Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.Type: GrantFiled: June 29, 2012Date of Patent: August 19, 2014Assignee: Rani Therapeutics, LLCInventor: Mir Imran
-
Publication number: 20140228285Abstract: The present invention regards an insulin derivative comprising at least 2 albumin binding moieties, wherein said albumin binding moieties comprise fatty diacid substitutions and a method for preparing such an insulin derivative by acylation and/or reductive alkylation. The present invention also concern a pharmaceutical comprising such an insulin derivative.Type: ApplicationFiled: June 14, 2012Publication date: August 14, 2014Applicant: NOVO NORDISK A/SInventors: Thomas Hoeg-Jensen, Peter Madsen, Jane Spetzler, Tina Moeller Tagmose
-
Patent number: 8802816Abstract: The invention relates to methods of separation and/or purification of impurities yielding a purified heterologous protein product devoid of related impurities or with substantially minimal quantities of such glycosylated impurities. More specifically, the invention relates to the identification of glycosylated forms of insulin analogues such as glargine impurities characterized post expression in yeast based systems such as Pichia pastoris. The invention also relates to methods used to clone gene encoding the protein insulin glargine; inserting the related gene in a suitable yeast host; producing culture of the recombinant strain, stimulating expression of the heterologous polypeptide, its secretion and purification post fermentation and related enzymatic conversions.Type: GrantFiled: April 3, 2008Date of Patent: August 12, 2014Assignee: Biocon LimitedInventors: Partha Hazra, Nitesh Dave, Vivekanandan Kannan, Sanjay Tiwari, Anuj Goel, Harish Iyer, Nita Roy, Krishnamurthy Venkatesan, Anoop Vasudevan, Anupama Jagadish, Goldy Sachdev, Mukesh Babuappa Patale
-
Publication number: 20140221606Abstract: Aspart modified proinsulin sequences that have a modified C-peptide amino acid and/or nucleic acid modification for producing aspart insulin analogs are provided. Highly efficient processes for preparing the aspart insulin analogs and improved preparations containing the aspart insulin analogs prepared according to the methods described herein are also provided.Type: ApplicationFiled: January 14, 2013Publication date: August 7, 2014Applicant: ELONA BIOTECHNOLOGIES INC.Inventor: Elona Biotechnologies Inc.
-
Publication number: 20140220633Abstract: The current invention reports a method for the purification of a not-glycosylated, heterologous polypeptide, which has been recombinantly produced in a prokaryotic cell, wherein the method comprises three chromatography steps of which the first chromatography step selected from i) hydrophobic charge induction chromatography, or ii) hydrophobic interaction chromatography, or iii) affinity chromatography, or iv) ion exchange chromatography, the second chromatography step is selected from i) anion exchange chromatography, or ii) cation exchange chromatography, or iii) hydroxylapatite chromatography, or iv) hydrophobic interaction chromatography, and the a third chromatography step is selected from i) hydrophobic charge induction chromatography, or ii) anion exchange chromatography, or iii) cation exchange chromatography, or iv) hydrophobic interaction chromatography, whereby the first chromatography step is an affinity chromatography in case of polypeptides capable of interacting with metal ligands, the second cType: ApplicationFiled: April 7, 2014Publication date: August 7, 2014Applicant: HOFFMANN-LA ROCHE INC.Inventors: Roberto Falkenstein, Birgit Weydanz, Nicole Fuehrler, Claudia Giessel, Sybille Gabel, Adelbert Grossmann, Friederike Hesse, Marc Pompiati, Andreas Schaubmar, Brigitte Kraemer
-
Patent number: 8796205Abstract: Novel human insulin derivatives are described which are soluble at physiological pH values and have a prolonged profile of action.Type: GrantFiled: May 8, 2007Date of Patent: August 5, 2014Assignee: Novo Nordisk A/SInventors: Ib Jonassen, Patrick William Garibay, Janos Tibor Kodra
-
Publication number: 20140213514Abstract: Novel pro-insulin having specific amino acid and/or nucleic acid modifications suitable for improved methods of insulin production are provided. Novel and highly efficient processes for preparing the pro-insulin preparations and preparations containing them are also disclosed. The novel pro-insulin preparations may be converted into human insulin useful in therapeutic preparations. Novel peptides of the C-peptide, and N terminus, including RREAEALQVGQVELGGGPGAGSLQPLALEGSLQAR, and MHHHHHHGGR respectively are provided, as well as the unique nucleic acid molecules encoding them.Type: ApplicationFiled: January 25, 2013Publication date: July 31, 2014Applicant: ELONA BIOTECHNOLOGIES, INC.Inventor: Elona Biotechnologies, Inc.
-
Publication number: 20140213756Abstract: Disclosed herein are novel and improved preparations and methods for manufacturing substantially liquid preparations of recombinant human insulin API. The purified recombinant human insulin Active Pharmaceutical Ingredient (API) preparations are substantially free of by-products associated with the lyophilization and/or crystallization. The methods for manufacturing the substantially liquid recombinant human insulin API preparations are provided with optional steps for subjecting the recombinant insulin preparation to lyophilization and/or crystallization. Enhanced yield of recombinant insulin of greater purity are thereby provided according to the present invention. Highly purified formulations of recombinant human insulin of the API insulin preparations disclosed herein are also provided. Stably transformed E.Type: ApplicationFiled: January 25, 2013Publication date: July 31, 2014Applicant: ELONA BIOTECHNOLOGIES, INC.Inventor: Elona Biotechnologies, Inc.
-
Patent number: 8790704Abstract: Nanoparticles having a core and a corona of ligands covalently linked to the core, wherein differing species of peptides are bound to the nanoparticles and incorporated into various dosage forms.Type: GrantFiled: June 8, 2012Date of Patent: July 29, 2014Assignees: Monosol RX, LLC, Midatech LimitedInventors: Phillip Williams, Thomas Rademacher, Alexander Mark Schobel, Eric Dadey
-
Patent number: 8748570Abstract: A dicarba analogue of insulin comprising an A-chain and a B-chain or fragments, salts, solvates, derivatives, isomers or tautomers of the A-chain, the B-chain or both, provided that the dicarba analogue is not [A7,B7-(2,7-diaminosuberoyl]-des-(B26-B30)-insulin B25-amide.Type: GrantFiled: May 25, 2011Date of Patent: June 10, 2014Assignee: Syngene LimitedInventors: Andrea Robinson, Bianca Van Lierop
-
Publication number: 20140155574Abstract: Disclosed is a method for preparing an insulin glargine (GlyA21-ArgB31-AryB32-human insulin) crystal, comprising crystallizing the insulin glargine at pH 7.0-9.0 and in a crystallization solution containing a recombinant insulin glargine, an organic solvent of a 10-30% concentration by volume, a zinc compound, a phenol derivative, a salt and an organic acid.Type: ApplicationFiled: April 19, 2012Publication date: June 5, 2014Applicant: GAN & LEE PHARMACEUTICALSInventors: Damei Wang, Wenjie Li, Jinlei Zhang
-
Patent number: 8735539Abstract: Modified relaxin polypeptides and their uses are provided. In one aspect, the disclosure provides a relaxin polypeptide comprising one or more non-naturally encoded amino acids. The polypeptide may be linked to a linker, polymer, or biologically active molecule. The serum half-life of the relaxin polypeptide may be enhanced relative to the unconjugated form. In another aspect, the disclosure provides methods of treating a patient having a disorder modulated by relaxin.Type: GrantFiled: August 17, 2011Date of Patent: May 27, 2014Assignee: Ambrx, Inc.Inventors: Vadim Kraynov, Nick Knudsen, Ahma Hewet, Kristine De Dios, Jason Pinkstaff, Lorraine Sullivan
-
Publication number: 20140128319Abstract: 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 or penta-fluoro-Phenylalanine at position B24 alone or in combination with an acidic substitution (Aspartic Acid or Glutamic Acid) at position B10. 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: October 4, 2013Publication date: May 8, 2014Applicant: Case Western Reserve UniversityInventor: Michael WEISS
-
Publication number: 20140121159Abstract: The present disclosure provides inter alia conjugates of formula (I): wherein n, R1, R2, Rx, Z, X, Y and Z are as defined herein. A conjugate of formula (I) can also be converted to a conjugate of formulae (II) or (III) as described herein. Without limitation, the conjugates can be used to make controlled release materials and chemical sensors.Type: ApplicationFiled: December 3, 2013Publication date: May 1, 2014Applicant: SmartCells, Inc.Inventors: Todd C. Zion, Thomas M. Lancaster
-
Publication number: 20140121352Abstract: Reversible pegylated drugs are provided by derivatization of free functional groups of the drug selected from amino, hydroxyl, mercapto, phosphate and/or carboxyl with groups sensitive to mild basic conditions such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), to which group a PEG moiety is attached. In these pegylated drugs, the PEG moiety and the drug residue are not linked directly to each other, but rather both residues are linked to different positions of the scaffold Fmoc or FMS structure that is highly sensitive to bases and is removable under physiological conditions. The drugs are preferably drugs containing an amino group, most preferably peptides and proteins of low or medium molecular weight. Similar molecules are provided wherein a protein carrier or another polymer carrier replaces the PEG moiety.Type: ApplicationFiled: January 2, 2014Publication date: May 1, 2014Applicant: YEDA RESEARCH AND DEVELOPMENT CO., LTD.Inventors: YORAM SHECHTER, MATITYAHU FRIDKIN, HAIM TSUBERY
-
Publication number: 20140121351Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.Type: ApplicationFiled: December 20, 2013Publication date: May 1, 2014Applicants: BAXTER HEALTHCARE SA, BAXTER INTERNATIONAL INC.Inventors: Stefan Haider, Andreas Ivens, Hanspeter Rottensteiner, Juregen Siekmann, Peter Turecek
-
Publication number: 20140121353Abstract: New biosynthetic analogues of recombined human insulin of prolonged therapeutical activity, which can find place in prophylactic and treatment of diabetes.Type: ApplicationFiled: November 26, 2013Publication date: May 1, 2014Applicant: INSTYTUT BIOTECHNOLOGII I ANTYBIOTYKOWInventors: Piotr BOROWICZ, Andrzej PLUCIENNICZAK, Jerzy MIKOLAJCZYK, Tadeusz GLABSKI, Dariusz KURZYNOGA, Diana MIKIEWICZ-SYGULA, Anna WOJTOWICZ-KRAWIEC, Marcin ZIELINSKI, Malgorzata KESIK-BRODACKA, Violetta ADAMCZEWSKA-CECUDA, Iwona SOKOLOWSKA, Grazyna PLUCIENNICZAK, Dorota STADNIK, Jaroslaw ANTOSIK, Jacek PSTRZOCH, Justyna BERNAT, Wojciech SLAWINSKI, Tomasz PAWLUKOWIEC, Jacek STEPNIEWSKI, Monika BOGIEL
-
Use of tris(hydroxymethyl) aminomethane for the stabilization of peptides, polypeptides and proteins
Patent number: 8710181Abstract: The present invention is directed to a method for reducing the onset or incidence of gelation/fibrillation/aggregation during the up- and down-stream processing and purification of peptides, polypeptides and proteins analogs and/or derivatives thereof, including Glucagon-Like Peptides (GLPs). More particularly, the present invention relates to methods of processing and purifying such peptides, polypeptides and proteins in the presence of tris(hydroxymethyl)aminomethane.Type: GrantFiled: August 26, 2005Date of Patent: April 29, 2014Assignee: Novo Nordisk A/SInventors: Ingun Christiansen, Arne Staby -
Patent number: 8697632Abstract: Prodrug formulations of insulin and insulin analogs are provided wherein the insulin peptide has been modified by an amide bond linkage of a dipeptide prodrug element. The prodrugs disclosed herein have extended half lives of at least 10 hours, and more typically greater than 2 hours, 20 hours and less than 70 hours, and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.Type: GrantFiled: December 18, 2009Date of Patent: April 15, 2014Assignee: Indiana University Research and Technology CorporationInventors: Richard D. DiMarchi, Binbin Kou, Shujiang Cheng
-
Patent number: 8697838Abstract: Prodrug formulations of bioactive polypeptides are provided wherein the bioactive polypeptide has been modified by the linkage of a dipeptide to the bioactive polypeptide through an ester linkage. The prodrugs disclosed herein in some embodiments have extended half lives of at least 1.5 hours (e.g., at least 10 hours), and more typically greater than 20 hours and less than 70 hours, and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.Type: GrantFiled: July 28, 2010Date of Patent: April 15, 2014Assignee: Indiana University Research and Technology CorporationInventors: Richard D. Dimarchi, Arnab De
-
Patent number: 8691189Abstract: The present disclosure describes techniques used for colorectal cancer detection. Position and distribution of colorectal cancer tumor are detected through nuclear imaging. Alternatively, stage of colorectal cancer is identified by shading value in tumor. Thus, the present disclosure provides a safe and noninvasive clinical method for diagnosing and tracing level and distribution of colorectal cancer before and after treatment.Type: GrantFiled: February 14, 2011Date of Patent: April 8, 2014Assignee: Institute of Nuclear Energy Research, Atomic Energy CouncilInventors: Siao-Syun Guan, Chun-Chia Cheng, Shui-Cheng Lee, Hsien-Ming Wu
-
Patent number: RE45313Abstract: The present invention relates to novel peptide conjugates which have increased stability and are useful in the treatment of excess levels of blood glucose.Type: GrantFiled: July 17, 2013Date of Patent: December 30, 2014Assignee: Zealand Pharma A/SInventors: Bjarne Due Larsen, Jens Damsgaard Mikkelsen, Søren Neve