Glucagon; Related Peptides Patents (Class 530/308)
  • Patent number: 9758562
    Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.
    Type: Grant
    Filed: September 8, 2015
    Date of Patent: September 12, 2017
    Assignee: Indiana University and Technology Corporation
    Inventors: Richard D. DiMarchi, David L. Smiley
  • Patent number: 9156902
    Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.
    Type: Grant
    Filed: June 12, 2012
    Date of Patent: October 13, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. DiMarchi, David L. Smiley
  • Patent number: 9102756
    Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.
    Type: Grant
    Filed: August 9, 2011
    Date of Patent: August 11, 2015
    Assignee: Trustees of Tufts College
    Inventors: William W. Bachovchin, Hung-sen Lai, David George Sanford
  • Publication number: 20150148289
    Abstract: A composition which includes oxyntomodulin and polyethylene glycol polymer (PEG polymer) linked via a reversible linker such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) is disclosed. Pharmaceutical compositions comprising the reverse pegylated oxyntomodulin and methods of using same are also disclosed.
    Type: Application
    Filed: June 4, 2013
    Publication date: May 28, 2015
    Inventors: Udi Eyal Fima, Oren Hershkovitz
  • Publication number: 20150133374
    Abstract: The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, respectively, of GLP-1(7-37) (SEQ ID NO: 1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4—O—(CH2)y—CO—*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NR1R2]—CO—*, which is connected at its CO—* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R1 and R2 independently represent *—H or *—CH3, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof.
    Type: Application
    Filed: May 2, 2013
    Publication date: May 14, 2015
    Inventors: Jacob Kofoed, Patrick W. Garibay, Jesper Lau
  • Publication number: 20150126440
    Abstract: Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming lactam bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, substitution of carboxy terminal amino acids, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (KRNRNNIA) and SEQ ID NO: 28 (KRNR).
    Type: Application
    Filed: November 7, 2014
    Publication date: May 7, 2015
    Inventors: Jonathan DAY, James PATTERSON, Joseph CHABENNE, Maria DiMARCHI, David L. SMILEY, Richard D. DiMARCHI
  • Publication number: 20150125431
    Abstract: GLP-2 analogues are disclosed which comprise one of more substitutions as compared to h[Gly2]GLP-2 and which may have the property of an altered GLP-1 activity, and their medical use. The analogues are particularly useful for the prophylaxis, treatment or ameliorating of the gastro-intestinal associated side effects of diabetes.
    Type: Application
    Filed: May 3, 2013
    Publication date: May 7, 2015
    Inventors: Rasmus Just, Kirsten Lindegaard Bovbjerg, Ditte Riber, Wayne Shaun Russell
  • Patent number: 9023985
    Abstract: There is provided according to the invention an aqueous composition having pH between 4 and 7 comprising (i) glucagon at a concentration of 0.05% w/v or more and (ii) a cationic surfactant selected from benzalkonium salts and benzethonium salts as solubilizing agent in an amount sufficient to dissolve the glucagon in the composition.
    Type: Grant
    Filed: March 15, 2013
    Date of Patent: May 5, 2015
    Assignee: Arecor Ltd.
    Inventors: Jan Jezek, Barry Kingston Derham
  • Patent number: 9018162
    Abstract: Disclosed is a method for treating or preventing hypoglycemia in a patient comprising administering an effective amount of a composition comprising a glucagon peptide which has been dried in a non-volatile buffer, and wherein the glucagon peptide has a pH memory that is about equal to the pH of the glucagon peptide in the non-volatile buffer, and an aprotic polar solvent, wherein the moisture content of the formulation is less than 5%, and wherein the dried glucagon peptide maintains the pH memory that is about equal to the pH of the glucagon peptide in the non-volatile buffer when the dried glucagon peptide is reconstituted in the aprotic polar solvent, wherein the patient has been diagnosed as having a blood glucose level between 0 mg/dL and less than 50 mg/dL or has an indication of impending hypoglycemia based on a blood glucose monitoring device before administration of the composition, and wherein the patient has a blood glucose level greater than 50 mg/dL to 180 mg/dL within 1 to 20 minutes after admin
    Type: Grant
    Filed: March 14, 2013
    Date of Patent: April 28, 2015
    Assignee: Xeris Pharmaceuticals, Inc.
    Inventor: Steven J. Prestrelski
  • Patent number: 9018164
    Abstract: Modified glucagon peptides are disclosed having improved solubility and stability, wherein the native glucagon peptide has been modified by pegylation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, or both.
    Type: Grant
    Filed: January 24, 2012
    Date of Patent: April 28, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. DiMarchi, David L. Smiley
  • Publication number: 20150111817
    Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.
    Type: Application
    Filed: October 16, 2014
    Publication date: April 23, 2015
    Inventors: Ditte RIBER, Jakob Lind TOLBORG, Dieter Wolfgang HAMPRECHT
  • Publication number: 20150111826
    Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel acylated glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.
    Type: Application
    Filed: October 17, 2014
    Publication date: April 23, 2015
    Inventors: Ditte RIBER, Jakob Lind TOLBORG, Dieter Wolfgang HAMPRECHT, Wolfgang RIST
  • Patent number: 9006178
    Abstract: The invention relates to a derivative of a GLP-1 analog, which analog comprises a first K residue at a position corresponding to position 18 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4-0-(CH2)y—CO—*, in which x is an integer in the range of 6-18, and y is an integer in the range of 3-17; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NH2]—CO—*, wherein q is an integer in the range of 0-5, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof.
    Type: Grant
    Filed: November 9, 2011
    Date of Patent: April 14, 2015
    Assignee: Novo Nordisk A/S
    Inventors: Jacob Kofoed, Jesper Lau, Lars Linderoth, Patrick William Garibay, Thomas Kruse
  • 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
  • Patent number: 8999930
    Abstract: The present invention relates to a soluble hydrophobic-core carrier composition comprising (i) a linear polymeric backbone; (ii) a plurality of hydrophilic polymeric protective chains covalently linked and pendant to the polymeric backbone and (iii) at least one hydrophobic moiety covalently linked and pendant to the polymeric backbone. In certain embodiments, the weight ratio of hydrophilic protective chains to hydrophobic moieties in the carrier is at least 15:1. In other embodiments, at least 90% of the residues of the polymeric backbone are coupled to a hydrophilic polymeric protective chain or a hydrophobic moiety. In other embodiments, the composition further comprises (iv) a hydrophobic load molecule dissociably linked to the hydrophobic moiety of the carrier.
    Type: Grant
    Filed: February 24, 2010
    Date of Patent: April 7, 2015
    Assignee: PharmaIN Corporation
    Inventors: Gerardo M. Castillo, Elijah M. Bolotin
  • Patent number: 8992886
    Abstract: Compositions, methods of using and methods of making a cyclic peptide analog imaging agent that includes at least portions of a peptide or protein that binds specifically to the GLP-1 receptor (GLP-1R) and the cyclic analog has one or more conformational restrictions including, but not limited to, lactam bridges, disulfide bridges, hydrocarbon bridges, and their combinations, salts and derivatives thereof wherein the cyclic analog is more stable than a non-cyclic analog when incubated in the presence of enzymes that degrade GLP-1 and have an increased serum half-live, wherein the cyclic analog comprises at least a portion of a GLP-1 peptide or at least a portion of an Exendin peptide salts, derivatives or combinations thereof.
    Type: Grant
    Filed: April 6, 2010
    Date of Patent: March 31, 2015
    Assignee: Board of Regents, the University of Texas System
    Inventors: Jung-Mo Ahn, Xiankai Sun
  • Publication number: 20150080295
    Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metabolic syndrome and associated disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.
    Type: Application
    Filed: March 3, 2014
    Publication date: March 19, 2015
    Applicant: Zealand Pharma A/S
    Inventors: Eddi MEIER, Ditte Riber, Marie Skovgaard, Bjarne Due Larsen, Jens Rosengren Daugaard
  • Patent number: 8981047
    Abstract: Glucagon antagonists are provided which comprise amino acid substitutions and/or chemical modifications to glucagon sequence. In one embodiment, the glucagon antagonists comprise a native glucagon peptide that has been modified by the deletion of the first two to five amino acid residues from the N-terminus and (i) an amino acid substitution at position 9 (according to the numbering of native glucagon) or (ii) substitution of the Phe at position 6 (according to the numbering of native glucagon) with phenyl lactic acid (PLA). In another embodiment, the glucagon antagonists comprise the structure A-B-C as described herein, wherein A is PLA, an oxy derivative thereof, or a peptide of 2-6 amino acids in which two consecutive amino acids of the peptide are linked via an ester or ether bond.
    Type: Grant
    Filed: October 23, 2008
    Date of Patent: March 17, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. Dimarchi, Bin Yang
  • Patent number: 8980830
    Abstract: Glucagon analogs are disclosed that exhibit both glucagon antagonist and GLP-1 agonist activity. In one embodiment, the glucagon antagonist/GLP-1 agonist comprises a modified amino acid sequence of native glucagon, in which the first one to five N-terminal amino acids of native glucagon is deleted and in which the alpha helix is stabilized.
    Type: Grant
    Filed: October 27, 2008
    Date of Patent: March 17, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. Dimarchi, Bin Yang, Chenguang Ouyang
  • Patent number: 8975227
    Abstract: The present invention provides a composition (e.g., a pharmaceutical composition) comprising at least one delivery agent compound and glucagon. Preferably, the composition includes a therapeutically effective amount of glucagon and the delivery agent compound. The composition of the present invention facilitates the delivery of glucagon and increases its bioavailability compared to administration without the delivery agent compound.
    Type: Grant
    Filed: July 17, 2006
    Date of Patent: March 10, 2015
    Assignee: Emisphere Technologies, Inc.
    Inventors: Nai Fang Wang, Puchun Liu, Steven Dinh, Michael M. Goldberg, Ehud Arbit
  • Patent number: 8969294
    Abstract: Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming intramolecular bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, acylation, alkylation, substitution of carboxy terminal amino acids, C-terminal truncation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (KRNRNNIA) and SEQ ID NO: 28 (KRNR).
    Type: Grant
    Filed: August 6, 2012
    Date of Patent: March 3, 2015
    Assignees: Istituto di Recerche di Biologia Molecolare P. Angeletti S.R.L., Indiana University Research and Technology Corporation
    Inventors: Elisabetta Bianchi, Antonello Pessi, Jonathan Day, Richard Dimarchi, David Smiley
  • Patent number: 8969288
    Abstract: Prodrug formulations of glucagon superfamily peptides are provided wherein the glucagon superfamily peptide has been modified by the linkage of a dipeptide to the glucagon superfamily through an amide bond linkage. The prodrugs disclosed herein have extended half lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.
    Type: Grant
    Filed: December 18, 2009
    Date of Patent: March 3, 2015
    Assignee: Indiana University Research and Technology Corporation
    Inventors: Richard D. DiMarchi, Binbin Kou
  • Publication number: 20150057221
    Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein -D is an amine containing biologically active moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I): wherein the dashed line indicates the attachment to the amine of the biologically active moiety and wherein R1, R1a, R2, R2a, R3, R3a, X, X1, X2, X3 have the meaning as indicated in the description and the claims and wherein L1 is substituted with one to four groups L2-Z and optionally further substituted, provided that the hydrogen marked with the asterisk in formula (I) is not replaced by a substituent; wherein L2 is a single chemical bond or a spacer; and Z is a carrier group. The invention also relates to A-L, wherein A is a leaving group, pharmaceutical composition comprising said prodrugs and their use as medicaments.
    Type: Application
    Filed: October 30, 2014
    Publication date: February 26, 2015
    Inventors: Felix Cleemann, Ulrich Hersel, Silvia Kaden, Harald Rau, Thomas Wegge
  • Publication number: 20150051141
    Abstract: This invention relates to novel compositions comprising analogs of glucagon, wherein the analog comprises an ?-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways, including diabetes and other metabolic disorders. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.
    Type: Application
    Filed: April 5, 2012
    Publication date: February 19, 2015
    Applicant: Longevity Biotech, Inc.
    Inventors: Scott Shandler, Samuel H. Gellman
  • Publication number: 20150051372
    Abstract: The present invention relates to the field of biomedicine, and in particular, to a method for purifying solid-phase synthetic crude liraglutide. The method comprises: dissolving solid-phase synthetic crude liraglutide in an aqueous acetonitrile solution to obtain a crude peptide solution; and obtaining liraglutide with high purity and high yield through four-step HPLC purification.
    Type: Application
    Filed: January 29, 2013
    Publication date: February 19, 2015
    Applicant: HYBIO PHARMACEUTICAL CO., LTD.
    Inventors: Liangzheng Qin, Junfeng Pan, Yaping Ma, Jiancheng Yuan
  • Patent number: 8951959
    Abstract: Provided is a glucagon-like peptide-1 (GLP-1) analog shown as the following formula, wherein X is selected from glycine and glycinamide. The GLP-1 analog has a non-proteogenic amino acid residue in position 8 relative to the sequence GLP-1, and is acylated with a moiety comprising two acidic groups to the lysine residue in position 26. The GLP-1 analog is resistant to dipeptidyl peptidase IV so as to have an extended half-life in vivo. Also provided is a use of the GLP-1 analog in conquering blood sugar.
    Type: Grant
    Filed: April 29, 2011
    Date of Patent: February 10, 2015
    Assignee: Betta Pharmaceuticals Co., Ltd.
    Inventors: Yinxiang Wang, Fenlai Tan, Shaojing Hu, Xiangdong Zhao, Cunbo Ma, Yanping Wang, Xiaoyan Shen, Lieming Ding, Yunyan Hu, Hong Cao, Wei Long
  • Patent number: 8946149
    Abstract: The present invention relates generally to the novel use of cardioprotective incretin compounds (CICs) such as GLP-1 and exendin and agonists thereof, including analogs and derivatives to prevent, delay, attenuate, or ameliorate cardiac remodeling. The present invention relates to methods for using CICs for the treatment of conditions associated with cardiac remodeling. The present invention further relates to methods for using CICs for the reduction of the risk or severity of congestive heart failure.
    Type: Grant
    Filed: April 11, 2006
    Date of Patent: February 3, 2015
    Assignees: Amylin Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals LP
    Inventors: Christen Anderson, Que Liu
  • Publication number: 20150025003
    Abstract: The invention relates to protracted Glucagon-Like Peptide-1 (GLP-1) derivatives and therapeutic uses thereof. The GLP-1 derivative of the invention comprises a modified GLP-1(7-37) sequence having a total of 2-12 amino acid modifications, including Glu22 and Arg26, and being derivatised with an albumin binding residue or pegylated in position 18, 20, 23, 30, 31, 34, 36, 37, or 39. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, stable, have long half-lives, a high affinity of binding to albumin, and/or a high affinity of binding to the extracellular domain of the GLP-1 receptor (GLP-1R), all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.
    Type: Application
    Filed: October 3, 2014
    Publication date: January 22, 2015
    Inventors: Jane Spetzler, Lauge Schaeffer, Jesper Lau, Thomas Kruse, Patrick W. Garibay, Steffen Reedtz-Runge, Henning Thoegersen, Ingrid Pettersson
  • Patent number: 8933039
    Abstract: Analogs of glucagon-like peptide 2, a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described.
    Type: Grant
    Filed: June 15, 2010
    Date of Patent: January 13, 2015
    Assignees: NPS Pharmaceuticals, Inc., 1149336 Ontario Inc.
    Inventors: Daniel J Drucker, Anna E. Crivici, Martin Sumner-Smith
  • Publication number: 20150011462
    Abstract: The invention relates to derivatives of GLP-1 like peptides which are C-terminally extended analogues of native GLP-1. The derivatives comprise two side chains, one at a position corresponding to position 42, and one at a position corresponding to position 18, 23, 27, 31, 36, or 38, wherein both positions are when compared to GLP-1(7-37). The side chains comprise a C19, C20, or C22 diacid protracting moiety and optionally a linker. The invention also relates to intermediate products in the form of novel GLP-1 analogues incorporated in the derivatives of the invention, as well as pharmaceutical compositions and medical uses of the derivatives. The derivatives have very long half-lives while maintaining a satisfactory potency, which makes them potentially suitable for once-monthly administration.
    Type: Application
    Filed: July 2, 2014
    Publication date: January 8, 2015
    Inventors: Steffen Reedtz-Runge, Jacob Kofoed, Christian Wenzel Tornoee, Per Sauerberg
  • Publication number: 20140378375
    Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.
    Type: Application
    Filed: June 23, 2014
    Publication date: December 25, 2014
    Inventors: Samuel H. Gellman, Lisa M. Johnson, Alan Attie, Mark P. Keller, Alan Saghatelian
  • Publication number: 20140371148
    Abstract: Peptide-peptidase inhibitor conjugate molecules are disclosed. These conjugate molecules are useful as agents for the treatment and prevention of metabolic and cardiovascular diseases, disorders, and conditions. Such diseases, conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, and other diabetes-related disorders.
    Type: Application
    Filed: June 18, 2014
    Publication date: December 18, 2014
    Inventors: Soumitra S. GHOSH, Josue ALFARO-LOPEZ, Lawrence J. D'Souza, Odile Esther LEVY, Qing LIN, Christopher J. SOARES
  • Publication number: 20140357552
    Abstract: The present invention provides a novel peptide compound having an activating action on GLP-1 receptors and GIP receptors and use of the peptide compound as a medicament. Specifically, a peptide containing a partial sequence represented by the formula (I) or a salt thereof and a medicament comprising the same are provided. (I) P1-Tyr-Aib-Glu-Gly-Thr-?MePhe-Thr-Ser-Asp-Tyr- A11-A12-A13-Leu-Asp-A16-A17-Ala-Gln-A20-Glu- Phe-Val-Lys-Trp-Leu-Leu-Lys-A29 wherein each symbol is as defined herein.
    Type: Application
    Filed: May 27, 2014
    Publication date: December 4, 2014
    Applicant: Takeda Pharmaceutical Company Limited
    Inventors: Taiji ASAMI, Ayumu NIIDA
  • Patent number: 8901484
    Abstract: 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: Grant
    Filed: April 25, 2013
    Date of Patent: December 2, 2014
    Assignee: Sanofi-Aventis Deutschland GmbH
    Inventors: Martin Vogel, Werner Mueller
  • Publication number: 20140349922
    Abstract: Pegylated and reverse pegylated GLP-1/Glucaron receptor agonists including pharmaceutical compositions comprising the same and methods of using the same are disclosed.
    Type: Application
    Filed: June 4, 2012
    Publication date: November 27, 2014
    Inventors: Udi Eyal Fima, Oren Hershkóvitz
  • Publication number: 20140349928
    Abstract: Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.
    Type: Application
    Filed: May 17, 2012
    Publication date: November 27, 2014
    Applicant: Mederis Diabetes, LLC
    Inventor: John J. Nestor
  • Patent number: 8895694
    Abstract: The invention relates to protracted Glucagon-Like Peptide-1 (GLP-1) derivatives and therapeutic uses thereof. The GLP-1 derivative of the invention comprises a modified GLP-1(7-37) sequence having a total of 2-12 amino acid modifications, including Glu22 and Arg26, and being derivatised with an albumin binding residue or pegylated in position 18, 20, 23, 30, 31, 34, 36, 37, or 39. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, stable, have long half-lives, a high affinity of binding to albumin, and/or a high affinity of binding to the extracellular domain of the GLP-1 receptor (GLP-1R), all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.
    Type: Grant
    Filed: September 5, 2008
    Date of Patent: November 25, 2014
    Assignee: Novo Nordisk A/S
    Inventors: Jane Spetzler, Lauge Schäffer, Jesper Lau, Thomas Kruse, Patrick William Garibay, Steffen Reedtz-Runge, Henning Thøgersen, Ingrid Pettersson
  • Publication number: 20140336107
    Abstract: The present invention relates, inter alia, to certain peptide conjugates, and to the use of the conjugates in the treatment of a variety of diseases or disorders, including diabetes (type 1 and/or type 2) and diabetes-related diseases or disorders.
    Type: Application
    Filed: November 2, 2012
    Publication date: November 13, 2014
    Inventors: Jakob Lind Tolborg, Trine Neerup, Keid Fosgerau, Torben Østerlund, Dorthe Lennert Christensen Almholt, Lone Frost Larsen
  • Publication number: 20140336356
    Abstract: Novel peptide agonists of GLP-1 activity useful for lowering blood glucose levels. The novel peptides comprise variants of the GLP-1 or the exendin-4 polypeptide sequence and are pharmacologically active and stable. These peptides are useful in the treatment of diseases that benefit from regulation of excess levels of blood glucose and/or regulation of gastric emptying, such as diabetes and eating disorders.
    Type: Application
    Filed: December 3, 2013
    Publication date: November 13, 2014
    Applicant: Zealand Pharma A/S
    Inventors: Bjarne D. LARSEN, Jens D. Mikkelsen, Søren Neve
  • Publication number: 20140336118
    Abstract: A peptide of the formula R1-NH-HAEGTFTSDVSSYLEGQAAKEFIAWLVK-CONR2R3 wherein R=H or an organic compound comprising from 1 to 10 carbon atoms and R2 R3=independently H or an alkyl group of 1 to 4 carbon atoms; or certain analogues of said GLP-1 peptide can be used for the treatment and prophylaxis of heart ischemia-reperfusion injury
    Type: Application
    Filed: October 29, 2012
    Publication date: November 13, 2014
    Inventors: Marek Treiman, Henrik K. Salling, Klaus Döhler, Thomas Engstrøm
  • Patent number: 8883963
    Abstract: The present invention provides novel peptidomimetics, of formula (I), which primarily act as glucose dependent insulin secretagogues. Furthermore, it was found that these peptidomimetics showed glucagon receptor antagonistic activity, along with the GLP-I receptor agonistic activity.
    Type: Grant
    Filed: December 10, 2008
    Date of Patent: November 11, 2014
    Assignee: Cadila Healthcare Limited
    Inventors: Rajesh H. Bahekar, Mukul R. Jain, Pankaj Ramanbhai Patel
  • Publication number: 20140309168
    Abstract: Provided are compounds and methods of making compounds containing two or three groups derived from a peptide, such as enfuvirtide or exenatide, covalently bound to a linker. The compounds may contain polyethylene glycol groups to enhance solubility and pharmacokinetic properties. The compounds are useful for the treatment of diseases or conditions subject to treatment with the parent peptide, such as HIV and AIDS in the case of enfuvirtide, or diabetes in the case of exenatide.
    Type: Application
    Filed: March 19, 2014
    Publication date: October 16, 2014
    Applicant: AmideBio, LLC
    Inventor: Mary S. Rosendahl
  • Publication number: 20140303083
    Abstract: The invention relates to a derivative of a GLP-1 peptide, which peptide has two Lys residues, namely a first and a second Lys residue, and a maximum of eight amino acid changes as compared to GLP-1(7-37) (SEQ ID NO: 3), which derivative comprises two protracting moieties attached to the epsilon amino group of said first and second Lys residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 15: HOOC—(CH2)x-CO—*, and Chem. 16: HOOC—C6H4-O—(CH2)y-CO—*, in which x is an integer in the range of 10-16, and y is an integer in the range of 8-12; and the linker comprises a first linker element *—NH—CH(CH2OH)—CO—*. A preferred linker is g Glu-Ser-Ser-Gly-Ser-Ser-Gly (SEQ ID NO: 2). The derivative of the invention has a very good potency, and a very good binding to the GLP-1 receptor. The invention also relates to the pharmaceutical use of the derivative, for example in the treatment and/or prevention of all forms of diabetes and related diseases.
    Type: Application
    Filed: September 6, 2012
    Publication date: October 9, 2014
    Applicant: NOVO NORDISK A/S
    Inventors: Jesper Lau, Paw Bloch, Jacob Kofoed, Patrick William Garibay
  • Patent number: 8853159
    Abstract: The present invention provides fusion peptides having GLP-1 activity and enhanced stability in vivo, in particular resistancy to dipeptidyl peptidase IV. The fusion peptide comprises as component (I) N-terminally a GLP-1(7-35, 7-36 or 7-37) sequence and as component (II) C-terminally a peptide sequence of at least 9 amino acids or a functional fragment, variant or derivative thereof. Component (II) is preferably a full or partial version of IP2 (intervening peptide 2). A preferred embodiment comprises the sequence GLP-1(7-35, 36 or 37)/IP2/GLP-1(7-35, 36 or 37) or GLP-2. The fusion peptide may be produced in engineered cells or synthetically and may be used for preparing a medicament for treating various diseases or disorders, e.g. diabetes type 1 or 2, apoptosis related diseases or neurodegenerative disorders.
    Type: Grant
    Filed: May 29, 2012
    Date of Patent: October 7, 2014
    Assignee: Biocompatibles UK Ltd
    Inventors: Peter Geigle, Christine Wallrapp, Eric Thoenes
  • Publication number: 20140296476
    Abstract: The present invention provides methods and compositions that permit controlled and prolonged drug release in vivo. The compounds are either prodrugs with tunable rates of release, or conjugates of the drug with macromolecules which exhibit tunable controlled rates of release.
    Type: Application
    Filed: March 21, 2014
    Publication date: October 2, 2014
    Inventors: Daniel V. SANTI, Gary W. ASHLEY
  • Patent number: 8846625
    Abstract: Analogs of glucagon-like peptide 2, a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described.
    Type: Grant
    Filed: March 11, 2013
    Date of Patent: September 30, 2014
    Assignee: 1149336 Ontario Inc.
    Inventors: Daniel J Drucker, Anna E. Crivici, Martin Sumner-Smith
  • Patent number: 8815802
    Abstract: The invention relates to a GLP-1 analog which comprises a histidine (H) residue at a position corresponding to position 31 of GLP-1(7-37) (SEQ ID NO: 1), a glutamine (Q) residue at a position corresponding to position 34 of GLP-1 (7-37) (SEQ ID NO: 1), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37) (SEQ ID NO: 1); wherein the H residue is designated H31, and the Q residue is designated Q34; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to derivatives thereof, as well as the pharmaceutical use of these analogs and derivatives, for example in the treatment and/or prevention of all forms of diabetes and related diseases. The invention furthermore relates to corresponding novel side chain intermediates. The derivatives are suitable for oral administration.
    Type: Grant
    Filed: December 16, 2010
    Date of Patent: August 26, 2014
    Assignee: Novo Nordisk A/S
    Inventors: Christoph Kalthoff, Jesper Lau, Jane Spetzler, Patrick William Garibay, Jacob Kofoed, Lars Linderoth
  • Publication number: 20140235535
    Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration, and reduced immunogenicity. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, Short Bowel Syndrome, Parkinson's disease, and cardiovascular disease.
    Type: Application
    Filed: July 3, 2012
    Publication date: August 21, 2014
    Inventors: Mary Erickson, David C. Litzinger, Soumitra S. Ghosh, Zijian Guo, Manoj P. Samant, Abhinandini Sharma, Lala Mamedova, Esther Odile Levy, Caroline Ekblad
  • Publication number: 20140228288
    Abstract: The present invention provides pharmaceutical compositions comprising at least one polypeptide having GLP-1 activity wherein an effective dose of said pharmaceutical composition comprises 15 mg, 30 mg, 50 mg or 100 mg of said polypeptide having GLP-1 activity. Also provided are methods of administering the pharmaceutical compositions of the invention.
    Type: Application
    Filed: April 25, 2014
    Publication date: August 14, 2014
    Applicant: GlaxoSmithKline, LLC
    Inventors: Mark A. BUSH, Murray W. Stewart, Yonghong Yang
  • Publication number: 20140221281
    Abstract: The present invention relates to exendin-4 derivatives and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.
    Type: Application
    Filed: December 20, 2013
    Publication date: August 7, 2014
    Applicant: Sanofi
    Inventors: Torsten HAACK, Michael Wagner, Bernd Henkel, Siegfried Stengelin, Andreas Evers, Martin Lorenz, Katrin Lorenz