Insulin; Related Peptides Patents (Class 530/303)
  • Patent number: 10946102
    Abstract: Disclosed herein is a glucose-responsive insulin delivery system based on the interaction between the glucose-modified insulin and glucose transporters (GLUTs) on erythrocytes (or red blood cells, RBCs). After being conjugated with glucose, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of blood glucose (BG) level in vivo. In some embodiments, the delivery vehicle can include: 1) intravenously injectable polymeric nanoparticles (˜100 nm in diameter) coated with RBC membrane and loaded with glucose-modified insulin and/or 2) painless microneedle (MN) patches loaded with the complex of GLUT and glucose-modified insulin.
    Type: Grant
    Filed: January 17, 2017
    Date of Patent: March 16, 2021
    Assignee: North Carolina State University
    Inventors: Zhen Gu, Chao Wang
  • Patent number: 10858390
    Abstract: An improved method of coupling amino acids into peptides or peptidomimetics is disclosed in which the activation and coupling are carried out in the same vessel, in the presence of a carbodiimide in an amount greater than 1 equivalent as compared to the amino acid, in the presence of an activator additive, and at a temperature greater than 30° C.
    Type: Grant
    Filed: August 25, 2017
    Date of Patent: December 8, 2020
    Assignee: CEM Corporation
    Inventors: Jonathan M. Collins, Sandeep K. Singh
  • Patent number: 10766940
    Abstract: Amylin receptor antagonists capable of binding to the amylin receptor and inhibiting activity of amylin or amyloid-beta protein are provided. The amylin receptor antagonists can be administered in the form of pharmaceutical compositions or the like. Methods for preparing and using the amylin receptor antagonists for treating, preventing, or ameliorating Alzheimer's disease are also provided.
    Type: Grant
    Filed: September 15, 2017
    Date of Patent: September 8, 2020
    Assignee: The Governors of the University of Alberta
    Inventors: Jack Jhamandas, Rania Soudy, Kamaljit Kaur, Wen Fu, David MacTavish, Aarti Patel
  • Patent number: 10660972
    Abstract: Described herein are methods of making targeting peptides conjugated to a recombinant lysosomal enzyme by modifying the amino (N)-terminus and one or more lysine residues on a recombinant human lysosomal enzyme using a first crosslinking agent to give rise to a first crosslinking agent modified recombinant human lysosomal enzyme, modifying a lysine or cysteine within a short extension linker at the carboxyl (C)-terminus on a variant IGF-2 peptide having a short extension linker using a second crosslinking agent to give rise to a second crosslinking agent modified variant IGF-2 peptide, and then conjugating the first crosslinking agent modified recombinant human lysosomal enzyme to the second crosslinking agent modified variant IGF-2 peptide containing a short extension linker. Also described herein are conjugates synthesized using the methods disclosed herein. Also described herein are treatment methods using the disclosed conjugates.
    Type: Grant
    Filed: November 9, 2016
    Date of Patent: May 26, 2020
    Assignee: Amicus Therapeutics, Inc.
    Inventor: Hung Do
  • Patent number: 10597435
    Abstract: The present disclosure relates generally to compositions of insulin-Fc (e.g., proinsulin-Fc) fusion proteins and their use to treat autoimmune disease, e.g., autoimmune diabetes, e.g., Type 1 diabetes.
    Type: Grant
    Filed: June 12, 2019
    Date of Patent: March 24, 2020
    Assignee: Akston Biosciences Corporation
    Inventors: Thomas M. Lancaster, Todd C. Zion, Thillainayagam Sathiyaseelan, Sylaja Murikipudi
  • Patent number: 10519215
    Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
    Type: Grant
    Filed: May 10, 2018
    Date of Patent: December 31, 2019
    Assignee: Immatics Biotechnologies GmbH
    Inventors: Andrea Mahr, Toni Weinschenk, Oliver Schoor, Jens Fritsche, Harpreet Singh, Lea Stevermann
  • Patent number: 10514382
    Abstract: A facile laboratory-based method and kit for use in accordance with the method is disclosed. The method allows for the localisation of biomolecules comprising a conjugatable sulfhydryl group to be localised to the surface of cells, such as red blood cells, as lipid conjugates. The method obviates the need to purify the lipid-conjugated biomolecule before contacting with the cells.
    Type: Grant
    Filed: January 29, 2018
    Date of Patent: December 24, 2019
    Inventors: Nikolai Vladimirovich Bovin, Stephen Micheal Henry, Ludmila Baidakova Rodionov
  • Patent number: 10441717
    Abstract: A physiological parameter associated with tissue of a host may be monitored in the tissue to confirm subcutaneous delivery of medication to the host. More particularly, such may involve delivering medication subcutaneously to the host with a medical device which includes a sensor used to measure the physiological parameter, particularly within a predetermined time period after delivery of the medication. Such may also or otherwise involve forming a depot in the tissue with the medication, and using the sensor to measure the physiological parameter while the sensor is at least partially within the depot.
    Type: Grant
    Filed: April 15, 2014
    Date of Patent: October 15, 2019
    Assignee: Insulet Corporation
    Inventors: Kevin Guido Schmid, Steven Dilanni, Robert W. Campbell, Ian T. McLaughlin, Jason B. O'Connor
  • Patent number: 10421795
    Abstract: A process is described for purifying insulin and insulin analogs that comprises high-pressure liquid chromatography with an acidic cation exchange medium performed under low to moderate pressure at an elevated temperature.
    Type: Grant
    Filed: December 12, 2013
    Date of Patent: September 24, 2019
    Assignee: Merck Sharp & Dohme Corp.
    Inventors: Michael P. Coleman, Allison D. Ortigosa, Mark C. Sleevi, Kartoa Chow
  • Patent number: 10413615
    Abstract: The present invention provides a novel process for preparing a cell-binding agent cytotoxic agent conjugate. The process comprises the steps of: (a) reacting a cytotoxic agent with a bifunctional crosslinking reagent represented by the structural formula (I) or a salt thereof, in a buffer solution comprising a buffering agent to provide a first mixture comprising a cytotoxic agent-linker compound, wherein the buffer solution has high buffer capacity; and (b) reacting the first mixture comprising the cytotoxic agent-linker compound from step (a) with a cell-binding agent in a solution having a pH of 4 to 9 to provide a second mixture comprising the cell-binding agent cytotoxic agent conjugate. The cell-binding agent cytotoxic agent conjugates prepared according to the processes described herein are also included in the present invention.
    Type: Grant
    Filed: November 18, 2015
    Date of Patent: September 17, 2019
    Assignee: IMMUNOGEN, INC.
    Inventor: Benjamin M. Hutchins
  • Patent number: 10352920
    Abstract: Methods for monitoring and adjusting a physiological state of a subject. The methods include (1) providing a subject having one or more physiological parameters defined by one or more biometrics, (2) monitoring a selected biometric analyte associated with a selected biometric to define a state of the selected biometric, (3) based on the results of the monitoring, adjusting the state of the selected biometric by administering to the subject a supplement selected to affect the state of the selected biometric.
    Type: Grant
    Filed: December 20, 2013
    Date of Patent: July 16, 2019
    Assignee: i-calQ, LLC
    Inventor: Joel R. L. Ehrenkranz
  • Patent number: 9932381
    Abstract: The present invention relates to glucagon receptor agonists and their medical use, for example in the treatment of severe hypoglycemia.
    Type: Grant
    Filed: June 12, 2015
    Date of Patent: April 3, 2018
    Assignee: Sanofi
    Inventors: Torsten Haack, Siegfried Stengelin, Andreas Evers, Michael Wagner, Bernd Henkel
  • Patent number: 9915653
    Abstract: Method of localizing a sulfhydryl (—SH) group containing biomolecule to the surface of a cell membrane by mixing in a volatile reaction buffer a molar excess of the sulfhydryl (—SH) group containing biomolecule with a lipid conjugated maleimide of the structure F-S-L as defined in the specification to provide a reaction mix, incubating the reaction mix for a time and at a temperature sufficient to allow all the lipid conjugated maleimide to have reacted with the sulfhydryl (—SH) group, and freeze-drying the reaction mix to remove the volatile reaction buffer and provide a reaction product. An aqueous solution of the reaction product is contacted with the cell membrane.
    Type: Grant
    Filed: August 31, 2012
    Date of Patent: March 13, 2018
    Inventors: Nikolai Vladimirovich Bovin, Stephen Michael Henry, Igor Leonidovich Rodionov
  • Patent number: 9789196
    Abstract: The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.
    Type: Grant
    Filed: April 21, 2015
    Date of Patent: October 17, 2017
    Assignee: ANTRIABIO, INC.
    Inventors: Kenneth Hinds, Danny Lewis, Paul Schmidt, Kathleen M. Campbell
  • Patent number: 9765118
    Abstract: As explained hereinbefore, the C12orf59 gene of the present invention suppresses cancer cell invasion and inhibits cancer cell survivability, and the over expression of C12orf59 protein or a fragment thereof inhibits cancer cell invasion, so that C12orf59 gene or a fragment thereof not only can be effectively used for the pharmaceutical composition for preventing and treating cancer but also can be used as a clinical marker for screening a cancer treatment agent candidate, for diagnosing various cancers or for predicting pathological stage. In addition, the C12orf59 gene or a fragment thereof of the present invention can be used for the method for preventing and treating cancer and for the preparation of a pharmaceutical composition for preventing and treating cancer.
    Type: Grant
    Filed: March 20, 2015
    Date of Patent: September 19, 2017
    Assignee: Korea Research Institute of Bioscience and Biotechnology
    Inventors: Semi Kim, Yunhee Lee
  • Patent number: 9603904
    Abstract: 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: Grant
    Filed: October 29, 2009
    Date of Patent: March 28, 2017
    Assignee: Novo Nordisk A/S
    Inventors: Thue Johansen, Birgitte Koch Michelsen, Berit Edsberg
  • Patent number: 9463249
    Abstract: 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: Grant
    Filed: May 19, 2014
    Date of Patent: October 11, 2016
    Assignee: SmartCells, Inc.
    Inventors: Thomas M. Lancaster, Todd C. Zion
  • Patent number: 9296806
    Abstract: The invention provides processes for obtaining a precursor for insulin, analogs or derivatives thereof having correctly bonded cystine bridges. The process involves solubilizing a precursor of insulin, insulin analog or derivatives in an aqueous solution or a buffer containing cysteine or cysteine hydrochloride and one or more of chaotropic auxiliary. The solubilized precursors are refolded by adding diluent to the solubilized mixture (reverse dilution). Further, the solubilized precursors, wherein the concentration of precursor in reaction mixture is more than 0.65 g/liter can also be refolded by diluting the reaction mixture with a diluent optionally comprising about 5-40% v/v of one or more of alcoholic or aprotic solvents.
    Type: Grant
    Filed: April 30, 2009
    Date of Patent: March 29, 2016
    Assignee: WOCKHARDT LIMITED
    Inventors: B Raju Edupuganti, Haseeb Jagirdar, Manish Kumar, Jayaraman Parthipan, Vivek Yadav, Maharaj K Sahib
  • Patent number: 9260501
    Abstract: Insulins to which there is connected an amino acid oligomer have satisfactory properties.
    Type: Grant
    Filed: October 29, 2007
    Date of Patent: February 16, 2016
    Assignee: Novo Nordisk A/S
    Inventors: Thomas Høeg-Jensen, Thomas Børglum Kjeldsen, Jan Markussen
  • Patent number: 9187520
    Abstract: 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: Grant
    Filed: April 19, 2012
    Date of Patent: November 17, 2015
    Assignee: Gan & Lee Pharmaceuticals
    Inventors: Damei Wang, Wenjie Li, Jinlei Zhang
  • Patent number: 9187547
    Abstract: The present invention relates to human insulin analogues containing a substituting cysteine, to human insulin derivatives containing a PEGylated substituting cysteine and methods of making such. The compounds of the invention may be useful for the treatment of diabetes.
    Type: Grant
    Filed: March 15, 2012
    Date of Patent: November 17, 2015
    Assignee: Novo Nordisk A/S
    Inventors: Tine Nygaard Vinther, Thomas Boerglum Kjeldsen, Frantisek Hubalek, Knud J. Jensen
  • Patent number: 9102758
    Abstract: An insulin conjugate is disclosed in which insulin is coupled to a modifying moiety of the formula X—R1—Y-PAG-Z—R2 wherein X, Y, and Z are linking groups, R2 is a capping group, and PAG is a carbon chain that incorporates one or more alkylene glycol moieties.
    Type: Grant
    Filed: January 18, 2011
    Date of Patent: August 11, 2015
    Assignee: BIOCON LIMITED
    Inventors: Balasingam Radhakrishnan, Diti Aggarwal, Michelle Ferro, Kenneth D. James, Navdeep B. Malkar, Mark A. Miller, Monica E. Puskas, Nnochiri N. Ekwuribe
  • Patent number: 9101596
    Abstract: 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: Grant
    Filed: January 24, 2011
    Date of Patent: August 11, 2015
    Assignee: BIOCON LIMITED
    Inventors: Balasingam Radhakrishnan, Diti Aggarwal, Michelle Ferro, Kenneth D. James, Navdeep B. Malkar, Mark A. Miller, Monica Puskas, Nnochiri N. Ekwuribe
  • Publication number: 20150148521
    Abstract: Acylated insulins wherein an acyl moiety is attached to the parent insulin and wherein said acyl moiety comprises repeating units of alkylene glycol containing amino acids and wherein there is only one lysine residue (K & Lys) in the parent insulin have satisfactory properties when administered pulmonary.
    Type: Application
    Filed: February 6, 2015
    Publication date: May 28, 2015
    Inventors: Peter Madsen, Thomas Boerglum Kjeldsen, Janos Tibor Kodra, Dorte Xenia Gram
  • Publication number: 20150147345
    Abstract: This document relates to conjugates of a biologically active molecule or a derivative thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.
    Type: Application
    Filed: June 12, 2013
    Publication date: May 28, 2015
    Inventor: Marek Kwiatkowski
  • Publication number: 20150148520
    Abstract: 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: Application
    Filed: December 8, 2014
    Publication date: May 28, 2015
    Inventors: Richard D. DiMARCHI, Yulia AZRIEL, Zachary KAUR, Jonathan MEYERS, Todd PARODY, Yan ZHAO
  • Patent number: 9035020
    Abstract: Acylated insulins wherein an acyl moiety is attached to the parent insulin and wherein the acyl moiety comprises repeating units of alkylene glycol containing amino acids and wherein there is only one lysine residue (K & Lys) in the parent insulin, having satisfactory properties when administered pulmonary.
    Type: Grant
    Filed: February 6, 2015
    Date of Patent: May 19, 2015
    Assignee: NOVO NORDISK A/S
    Inventors: Peter Madsen, Thomas Boerglum Kjeldsen, Janos Tibor Kodra, Dorte Xenia Gram
  • Patent number: 9034818
    Abstract: The invention concerns a soluble pharmaceutical formulation comprising an insulin derivative wherein the formulation further comprises more than 4 zinc atoms per 6 molecules of the insulin derivative, and a citric acid monohydrate and/or a histidine compound used in an amount sufficient to increase the tendency of the insulin derivative to self-associate into dodecamers. The invention further comprises a process for preparing the soluble pharmaceutical formulation.
    Type: Grant
    Filed: June 12, 2008
    Date of Patent: May 19, 2015
    Assignee: Novo Nordisk A/S
    Inventors: Christian Poulsen, Kasper Huus, Frantisek Hubalek, Dorte Bjerre Steensgaard, Svend Havelund
  • Publication number: 20150118185
    Abstract: Compositions containing conjugates of heparosan polymer with at least one drug are disclosed, along with methods of production and use thereof.
    Type: Application
    Filed: November 7, 2014
    Publication date: April 30, 2015
    Inventor: Paul L. DeAngelis
  • Publication number: 20150111820
    Abstract: This invention relates to insulin derivatives having long duration of action. The insulin derivatives have been found to be useful for the treatment of diabetes, and in particular for less frequent administration to the diabetic patients, in particular as seldom as about once weekly.
    Type: Application
    Filed: July 8, 2013
    Publication date: April 23, 2015
    Inventors: Lone Pridal, Helle Naver, Peter Madsen, Thomas Boerglum Kjeldsen
  • Publication number: 20150099698
    Abstract: 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: Application
    Filed: October 8, 2013
    Publication date: April 9, 2015
    Inventors: Phillip Williams, Thomas Rademacher, Alexander Mark Schobel, Eric Dadey
  • Publication number: 20150093370
    Abstract: The present invention provides albumin-binding probes capable of reversibly linking to short-lived amino-containing drugs and non-covalently associating with albumin in-vivo, thereby converting said drugs into inactive reactivable prodrugs having prolonged lifetime in-vivo. The invention further provides conjugates of said probes with amino-containing drugs, as well as pharmaceutical compositions and uses thereof.
    Type: Application
    Filed: December 9, 2014
    Publication date: April 2, 2015
    Inventors: Yoram SHECHTER, Matityahu FRIDKIN
  • Patent number: 8993516
    Abstract: 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.
    Type: Grant
    Filed: April 14, 2009
    Date of Patent: March 31, 2015
    Assignee: Case Western Reserve University
    Inventor: Michael Weiss
  • Patent number: 8987197
    Abstract: Novel PEGylated insulin analogs exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogs contain B25H and A14E or A14H. The PEGylation is at B29K.
    Type: Grant
    Filed: November 29, 2011
    Date of Patent: March 24, 2015
    Assignee: Novo Nordisk A/S
    Inventors: Peter Madsen, Thomas Hoeg-Jensen, Thomas Børglum Kjeldsen, Tina Møller Tagmose
  • Publication number: 20150079658
    Abstract: The present disclosure provides POZ derivatives having a range of active functional groups allowing conjugation of POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives. In one embodiment, the POZ derivative is a terminally activated monofunctional POZ derivative.
    Type: Application
    Filed: November 21, 2014
    Publication date: March 19, 2015
    Inventors: J Milton HARRIS, Michael David Bentley, Kunsang Yoon, Zhihao Fang, Francesco Maria Veronese, Tacey Viegas, Anna Mero
  • Publication number: 20150072396
    Abstract: Low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations for modifying biomolecules is provided. Compositions, methods, and kits relating to low-copper click chemistry, 1.3-dipolar cycloadditions, and Staudinger ligations are also provided.
    Type: Application
    Filed: March 1, 2012
    Publication date: March 12, 2015
    Applicant: LIFE TECHNOLOGIES CORPORATION
    Inventors: Kyle Gee, Upinder Singh, Scott Grecian, Scott Clarke
  • Publication number: 20150064720
    Abstract: The invention relates to biomolecules conjugated to graphene quantum dots, and in particular, to use of such biomolecule-graphene quantum dot conjugates as fluorophores for imaging applications.
    Type: Application
    Filed: August 28, 2014
    Publication date: March 5, 2015
    Inventors: Peng Chen, Xin Ting Zheng
  • Patent number: 8962553
    Abstract: The present invention relates to PEGylated C-peptide derivatives comprising at least one PEG group attached to the N-terminus, which exhibit improved pharmacokinetic and biological activity in vivo.
    Type: Grant
    Filed: November 19, 2012
    Date of Patent: February 24, 2015
    Assignee: Cebix AB
    Inventors: John Wahren, Sheri Barrack, James Callaway, Michelle Mazzoni, Howard Foyt, Mark Daniels
  • Patent number: 8962794
    Abstract: Acylated insulins wherein an acyl moiety is attached to the parent insulin and wherein said acyl moiety comprises repeating units of alkylene glycol containing amino acids and wherein there is only one lysine residue (K & Lys) in the parent insulin have satisfactory properties when administered pulmonary.
    Type: Grant
    Filed: August 15, 2008
    Date of Patent: February 24, 2015
    Assignee: Novo Nordisk A/S
    Inventors: Peter Madsen, Thomas Boerglum Kjeldsen, Janos Tibor Kodra
  • Publication number: 20150051371
    Abstract: Provided herein are water-soluble carbohydrate polymers which are monoderivatized at their reducing terminus, such that the carbohydrate polymers can be selectively conjugated at a single location. Also provided are methods of preparation and conjugation of the monoderivatized carbohydrate polymers.
    Type: Application
    Filed: January 29, 2014
    Publication date: February 19, 2015
    Applicant: NEKTAR THERAPEUTICS
    Inventors: Antoni Kozlowski, Samuel P. McManus, Xiaoming Shen
  • Patent number: 8951962
    Abstract: Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.
    Type: Grant
    Filed: May 17, 2013
    Date of Patent: February 10, 2015
    Assignees: Amylin Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals LP
    Inventors: Karthryn S. Prickett, Andrew A. Young
  • Publication number: 20150038411
    Abstract: A pharmaceutical composition for treatment for of r afflicted or in risk of becoming of impaired glucose tolerance (IGT) and/or type-2 it comprising an effective amount of relaxin for protecting beta-cells and beta-cell function against the effects of high blood glucose (glucotoxicity). Treatment of persons of disglycaemias, and protection of beta cells of the islets of Langerhans and beta-cell function in patients having type-2 diabetes, is diclosed.
    Type: Application
    Filed: February 22, 2013
    Publication date: February 5, 2015
    Applicant: Immundiagnostik AG
    Inventor: Thomas Dschietzig
  • Patent number: 8946148
    Abstract: Modified insulin polypeptides and their uses thereof are provided.
    Type: Grant
    Filed: November 20, 2008
    Date of Patent: February 3, 2015
    Assignee: 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
  • Patent number: 8946147
    Abstract: 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: Grant
    Filed: June 23, 2011
    Date of Patent: February 3, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. DiMarchi, Binbin Kou, Shujiang Cheng
  • Patent number: 8946380
    Abstract: With the aim of providing a liposome, having a hydrophilic polymer introduced into the outer surface of the liposome membrane, which is a liposome capable of allowing the liposome-entrapped substance to escape from the endosome and be released into the cytoplasm, a liposome membrane component bound to the peptide shown by (a) or (b) below and a liposome membrane component bound to one end of a hydrophilic polymer the other end of which is bound to the peptide shown by (a) or (b) below are included in the liposome: (a) a peptide comprising the amino acid sequence of SEQ ID NO:1; (b) a peptide comprising the amino acid sequence of SEQ ID NO:1 with 1 or more amino acids deleted, replaced or added therein, and capable of fusing lipid membranes with one another under acidic conditions.
    Type: Grant
    Filed: January 12, 2007
    Date of Patent: February 3, 2015
    Assignee: Japan Science and Technology Agency
    Inventors: Kentaro Kogure, Shiroh Futaki, Hideyoshi Harashima, Shigetada Chaki
  • Publication number: 20150031609
    Abstract: 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: Application
    Filed: October 13, 2014
    Publication date: January 29, 2015
    Inventors: Solomon S. Steiner, Rodney J. Woods, Joseph W. Sulner
  • Patent number: 8940860
    Abstract: 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: Grant
    Filed: June 16, 2011
    Date of Patent: January 27, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. DiMarchi, Julia Azriel, Zach Kaur, Jonathan Meyers, Todd Parody, Yan Zhao
  • Publication number: 20150024455
    Abstract: 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: Application
    Filed: July 17, 2014
    Publication date: January 22, 2015
    Inventors: Juergen Siekmann, Stefan Haider, Hanspeter Rottensteiner, Peter Turecek
  • Publication number: 20150017699
    Abstract: 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: Application
    Filed: July 9, 2014
    Publication date: January 15, 2015
    Applicant: NANOTECH BIOMACHINES, INC.
    Inventors: Jeffrey Alan McKinney, William Emerson Martinez
  • Patent number: 8933207
    Abstract: 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: Grant
    Filed: July 22, 2011
    Date of Patent: January 13, 2015
    Assignee: SmartCells, Inc.
    Inventors: Zhiyu Chen, Thomas M. Lancaster, Todd C. Zion