Glucagon; Related Peptides Patents (Class 530/308)
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Publication number: 20130030148Abstract: The present invention relates to a process for the large-scale synthesis of (Aib8,35)hGLP-1(7-36)-NH2 (SEQ ED NO:2), i.e., His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gb-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Aib-Arg-NH2 (SEQ ID NO:2), which comprises solid-phase Fmoc-chemistry.Type: ApplicationFiled: September 22, 2009Publication date: January 31, 2013Inventors: Zheng Xin Dong, Thomas Ciaran Loughman, Fionn Hurley, Steven R. Johnson
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Publication number: 20130012684Abstract: The present invention provides a method for purification of a protein that is conjugated to an albumin binding moiety from a mixture comprising (i) said protein in said conjugated form and (ii) said protein in a form that is not conjugated to said albumin-binding moiety, the method comprising: (a) providing a solid support comprising a substance capable of specifically binding to the albumin binding moiety; (b) contacting said solid support of (a) with said mixture comprising protein and conjugated protein under suitable conditions for binding of the albumin binding moiety to the substance as defined in (a); and (c) eluting components bound to the solid support.Type: ApplicationFiled: February 3, 2011Publication date: January 10, 2013Applicant: Novo Nordisk A/SInventor: Jens Buchardt
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Publication number: 20120329708Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.Type: ApplicationFiled: June 12, 2012Publication date: December 27, 2012Applicant: Indiana University Research and Technology CorporationInventors: Richard D. DiMARCHI, David L. SMILEY
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Publication number: 20120329711Abstract: The invention relates to GLP-1 receptor agonist compounds with a modified N-terminus. The compounds are of the formula Chem. 1: Y—Z—P, wherein P represents a fragment of a GLP-1 receptor agonist peptide lacking the two N-terminal amino acid residues; and Y—Z represents novel His-Ala mimetics. Examples of GLP-1 receptor agonist compounds are derived from human GLP-1 (7-37), exendin-4(1-39), or GLP-1 A (1-37). The invention also relates to derivatives of these compounds, in particular compounds with one or more albumin binding side chains capable of protracting the duration of action in vivo of these compounds. The peptides and derivatives of the invention have a good potency, a protracted pharmacokinetic profile, are stable against degradation by gastro intestinal enzymes, and/or have a high oral bioavailability. These properties are of importance in the development of GLP-1 receptor agonist compounds for subcutaneous, intravenous, and/or in particular oral administration.Type: ApplicationFiled: December 16, 2010Publication date: December 27, 2012Applicant: Nordisk A/SInventors: Janos Tibor Kodra, Johnny Madsen, Patrick William Garibay
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Publication number: 20120329707Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.Type: ApplicationFiled: June 12, 2012Publication date: December 27, 2012Applicant: Indiana University Research and Technology CorporationInventors: Richard D. DiMARCHI, David L. SMILEY, Bin YANG
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Patent number: 8338368Abstract: 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: GrantFiled: November 6, 2006Date of Patent: December 25, 2012Assignee: Indiana University Research and Technology CorporationInventors: Richard D. Dimarchi, David L. Smiley
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Publication number: 20120322976Abstract: A method for separating on a RP-HPLC system a polypeptide of interest from at least one unwanted component is described, wherein at least one of the elution steps is performed at or in close proximity to the pl value of the peptide of interest.Type: ApplicationFiled: March 1, 2011Publication date: December 20, 2012Applicant: NOVO NORDISK A/SInventors: Xiaoyan Wu, Are Bogsnes
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Publication number: 20120309936Abstract: Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.Type: ApplicationFiled: May 26, 2011Publication date: December 6, 2012Applicant: Merck Patent GmbHInventors: Stephen D. Gillies, Jeffrey Way, Anita A. Hamilton
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Publication number: 20120301535Abstract: 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: ApplicationFiled: June 8, 2012Publication date: November 29, 2012Inventors: Phillip Williams, Thomas Rademacher, Alexander Mark Schobel, Eric Dadey
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Patent number: 8318667Abstract: Glucagon receptor antagonist compounds are disclosed. The compounds are useful for treating type (2) diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.Type: GrantFiled: February 15, 2010Date of Patent: November 27, 2012Assignee: Merck Sharp & Dohme Corp.Inventors: Songnian Lin, Libo Xu, Edward Metzger, Emma R. Parmee, Sheryl D. Debenham
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Publication number: 20120295847Abstract: Protracted GLP-1 compounds and therapeutic uses thereof.Type: ApplicationFiled: March 5, 2012Publication date: November 22, 2012Applicant: Novo Nordisk A/SInventors: Jesper Lau, Florencio Zaragoza Dörwald, Henrik Stephensen, Paw Bloch, Thomas Kruse Hansen, Kjeld Madsen
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Publication number: 20120289466Abstract: GLP-2 analogues are disclosed which comprise one of more substitutions as compared to [hGly2]GLP-2 and which improved biological activity in vivo and/or improved chemical stability, e.g., as assessed in in vitro stability assays. More particularly, preferred GLP-2 analogues disclosed herein comprise substitutions at one or more of positions 8, 16, 24 and/or 28 of the wild-type GLP-2 sequence, optionally in combination with further substitutions at position 2 (as mentioned in the introduction) and one or more of positions 3, 5, 7, 10 and 11, and/or a deletion of one or more of amino acids 31 to 33 and/or the addition of a N-terminal or C-terminal stabilizing peptide sequence. The analogues are particularly useful for the prophylaxis or treatment of stomach and bowel-related disorders and for ameliorating side effects of chemotherapy. Also disclosed are methods and kits for selecting a patient from populations suited for treatment with GLP-2 analogues.Type: ApplicationFiled: June 28, 2012Publication date: November 15, 2012Applicant: Zealand Pharma A/SInventors: Bjarne Due Larsen, Yvette Miata Petersen
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Publication number: 20120289453Abstract: Novel GLP-1 compounds and their therapeutic use.Type: ApplicationFiled: May 16, 2012Publication date: November 15, 2012Applicant: Novo Nordisk A/SInventors: Nils Langeland Johansen, Jesper Lau, Kjeld Madsen, Thomas Kruse Hansen, Jeppe Sturis
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Publication number: 20120288511Abstract: Provided herein are glucagon analogs comprising a modified amino acid sequence of native human glucagon (SEQ ID NO: 2) that exhibit activity at the glucagon receptor, activity at the GLP-I receptor, or activity at each of the glucagon receptor and the GLP-I receptor. In some embodiments, the glucagon analog exhibits at least 100% or more of the activity of native glucagon at the glucagon receptor and/or at least 100% or more of the activity of native GLP-I at the GLP-I receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-I receptor which is within 50-fold or less than the EC50 at the glucagon receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-I receptor which is two- to ten-fold greater than the EC50 at the glucagon receptor. Related conjugates, dimers and multimers, and pharmaceutical compositions, and uses thereof, are further provided.Type: ApplicationFiled: December 9, 2010Publication date: November 15, 2012Applicant: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATIONInventor: Richard D. Dimarchi
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Publication number: 20120277154Abstract: Provided is a homodimer of insulinotropic peptide analogues and method for preparation thereof and use thereof, wherein the insulinotropic peptide analogue comprises GLP-1 and Exendin-4. The homodimer of insulinotropic peptide analogues of the invention is made by conjugating two identical insulinotropic peptide analogue molecules at the C-terminal Cys residues via disulfide bond or PEG molecule. The homodimer of insulinotropic peptide analogues of the invention has superior stability and biological activity in vivo, and prolonged half-life in the circulation, and can be used for the preparation of hypoglycemic drugs.Type: ApplicationFiled: March 15, 2010Publication date: November 1, 2012Applicant: CHONGQING FAGEN BIOMEDICAL INC.Inventors: Kai Fan, Zhiquan Zhao, Yong Chen, Chun Zhang, Lin Wang
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Patent number: 8293869Abstract: Conjugates of a GLP-I moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-I polymer conjugate may include a GLP-I moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached to a water-soluble polymer, wherein the GLP-I moiety possesses an N-methyl substituent. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached at a polymer attachment site to a water-soluble polymer, wherein the GLP-I moiety is glycosylated at a site separate from the polymer attachment site.Type: GrantFiled: December 18, 2006Date of Patent: October 23, 2012Assignee: Nektar TherapeuticsInventors: Mary J. Bossard, Zhihao Fang, Tacey X. Viegas, Stewart A. Thompson, Mei-chang Kuo
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Publication number: 20120264684Abstract: Disclosed is a glucagon-like peptide-1 (GLP-1) analogue which is obtained by ameliorating a highly antigenic GLP-1 analogue so that the GLP-1 analogue has reduced antigenicity without being lowered in the blood glucose suppressing activity. Specifically disclosed is a glycosylated form of an antigenic GLP-1 analogue, which has GLP-1 activity and is obtained by substituting at least one amino acid of an antigenic GLP-1 analogue with a glycosylated amino acid.Type: ApplicationFiled: October 25, 2010Publication date: October 18, 2012Inventors: Yasuhiro Kajihara, Takashi Tsuji, Yuri Nambu, Kazuyuki Ishii, Kenta Yoshida, Katsunari Tezuka
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Patent number: 8288338Abstract: Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.Type: GrantFiled: April 23, 2010Date of Patent: October 16, 2012Assignee: Amylin Pharmaceuticals, LLCInventors: Andrew A. Young, Sunil Bhavsar, Bronislava Gedulin
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Patent number: 8288339Abstract: GLP-1 compounds comprising GLP-1 analogs and methods of using the GLP-1 compounds for treating metabolic disorders, enhancing insulin expression, and promoting insulin secretion in a patient are provided.Type: GrantFiled: April 20, 2007Date of Patent: October 16, 2012Assignee: Amgen Inc.Inventors: Colin Victor Gegg, Jr., Leslie Phillip Miranda, Katherine Ann Winters, Murielle Veniant-Ellison
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Publication number: 20120252727Abstract: Described herein are compositions and methods useful for allowing for the absorption (passage) of agents of interest, such as therapeutic agents, across epithelial and mucosal barriers and/or into certain subcellular compartments of the cell, such as the recycling endosome (RE), Golgi, and the endoplasmic reticulum (ER).Type: ApplicationFiled: September 4, 2009Publication date: October 4, 2012Applicant: Children's Medical Center CorporationInventors: Wayne I. Lencer, Daniel JF Chinnapen, Randy Mrsny
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Patent number: 8278272Abstract: The invention relates to novel polypeptide analogues of GLP-1 and exendin-4. The polypeptide, in a preferred embodiment, is insulinotropic and long-acting. Preferably, the polypeptide's insulinotropic effect is comparable to or exceeds the effect of an equimolar amount of GLP-1 or exendin-4. The invention also relates to a method of treating a subject with diabetes, comprising administering to the subject the polypeptide of the invention in an amount that has an insulinotropic effect. The invention also relates to methods of using GLP-1, exendin-4, and polypeptide analogues thereof for neuroprotective and neurotrophic effects.Type: GrantFiled: December 18, 2008Date of Patent: October 2, 2012Assignee: The United States of America, as represented by the Secretary, Department of Health & Human ServicesInventors: Nigel Greig, Josephine Egan, Maire Doyle, Harold Holloway, Tracy Ann Perry
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Patent number: 8278273Abstract: The invention relates to glucagon-related peptides and their use for the prevention or treatment of disorders involving the large intestine. In particular, it has now been demonstrated that GLP-2 and peptidic agonists of GLP-2 can cause proliferation of the tissue of large intestine. Thus, the invention provides methods of proliferating the large intestine in a subject in need thereof. Further, the methods of the invention are useful to treat or prevent inflammatory conditions of the large intestine, including inflammatory bowel diseases.Type: GrantFiled: May 6, 2011Date of Patent: October 2, 2012Assignee: 1149336 Ontario, Inc.Inventor: Daniel J. Drucker
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Publication number: 20120244080Abstract: Glucagon-like peptide-1 (GLP-1) is a member of a large family of incretin hormones secreted in nutrient-dependent response. GLP-1 acts on GLP-1 receptor (GLP-1 R) that is highly expressed on pancreatic ?-cells. The peptide has great potential for development of diabetes treatment and diagnosis. However, the pharmaceutical effects of the peptide suffer from in vivo instability and short life due to degradation by Dipeptidylpeptidase-1 (DPP-4). The 30 amino acid peptide GLP-1 has been integrated into a stable host protein human calbindin D9k. The fusion protein binds to GLP-1 R as demonstrated by immunostaining analyses of GLP-1 R expressing cells. The fusion protein agents can be useful for both diabetes treatment and GLP-1 R receptor targeting MR imaging. The fusion protein has a size about 14 kDa, which enables efficient tissue penetration and retention, and an extended circulation time, is stable, remaining intact and retaining activity after 48 hours incubation with 75% human serum.Type: ApplicationFiled: October 20, 2010Publication date: September 27, 2012Inventors: Zhi-Ren Liu, Jie Yang, Bing Xu, Wangda Zhou, Shenghui Xue
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Patent number: 8273854Abstract: The invention provides specific GLP-1 analogs fused to specific IgG4-Fc derivatives. These fusion proteins have an increased half-life, decreased immunogenicity, and reduce effector activity. The fusion proteins are useful in treating diabetes, obesity, irritable bowel syndrome and other conditions that would be benefited by lowering plasma glucose, inhibiting gastric and/or intestinal motility and inhibiting gastric and/or intestinal emptying, or inhibiting food intake.Type: GrantFiled: October 31, 2008Date of Patent: September 25, 2012Assignee: Eli Lilly and CompanyInventors: Wolfgang Glaesner, Rohn Lee Millican, Jr., Andrew Mark Vick
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Publication number: 20120238493Abstract: Provided herein are glucagon analogs which exhibit potent activity at the GIP receptor, and, as such are contemplated for use in treating diabetes and obesity. In exemplary embodiments, the glucagon analog of the present disclosures exhibit an EC50 at the GIP receptor which is within the nanomolar or picomolar range.Type: ApplicationFiled: December 20, 2011Publication date: September 20, 2012Inventors: Richard D. DiMARCHI, Brian P. WARD
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Patent number: 8268780Abstract: Disclosed is a method of preparing a GLP-1 compound that is soluble in aqueous solution at pH 7.4 from a GLP-1 compound that is substantially insoluble in aqueous solution at pH 7.4. The insoluble GLP-1 compound is dissolved in aqueous base or in aqueous acid to form a GLP-1 solution. The GLP-1 solution is then neutralized to a pH at which substantially no amino acid racemization of the GLP-1 compounds occurs, after which the soluble GLP-1 compound is isolated from the neutralized solution.Type: GrantFiled: April 27, 2012Date of Patent: September 18, 2012Assignee: Eli Lilly and CompanyInventors: Walter Francis Prouty, Jr., Joseph Vincent Rinella, Jr.
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Patent number: 8268781Abstract: In the current invention peptides, which are derived from GLP-1 (glucagon-like peptide-1) and exendin-3 and/or exendin-4, are provided which bond to the GLP-receptor and can be used, labeled or unlabeled, for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role.Type: GrantFiled: March 2, 2007Date of Patent: September 18, 2012Assignee: Philipps-Universitat MarburgInventors: Martin Gotthardt, Martin Béhé, Thomas Behr, Burkhard J. Göke
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Publication number: 20120220011Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.Type: ApplicationFiled: February 14, 2012Publication date: August 30, 2012Applicant: Amunix Operating Inc.Inventors: Volker Schellenberger, Willem P. Stemmer, Chia-wei Wang, Michael D. Scholle, Mikhail Popkov, Nathaniel C. Gordon, Andreas Crameri
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Publication number: 20120208980Abstract: Disclosed is a method of preparing a GLP-1 compound that is soluble in aqueous solution at pH 7.4 from a GLP-1 compound that is substantially insoluble in aqueous solution at pH 7.4. The insoluble GLP-1 compound is dissolved in aqueous base or in aqueous acid to form a GLP-1 solution. The GLP-1 solution is then neutralized to a pH at which substantially no amino acid racemization of the GLP-1 compounds occurs, after which the soluble GLP-1 compound is isolated from the neutralized solution.Type: ApplicationFiled: April 27, 2012Publication date: August 16, 2012Applicant: ELI LILLY AND COMPANYInventors: Walter Francis Prouty, JR., Joseph Vincent Rinella, JR.
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Publication number: 20120196804Abstract: 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: ApplicationFiled: January 24, 2012Publication date: August 2, 2012Applicant: Indiana University Research and Technology CorporationInventors: Richard D. DiMARCHI, David L. SMILEY
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Publication number: 20120196798Abstract: This invention discloses GLP-1 analogues and their pharmaceutical salts, wherein the GLP-1 analogue comprises an amino acid sequence of general formula (I), wherein Lys represents a modified lysine with a lipophilic acid. The GLP-1 analogues provided by this invention have the function of human GLP-1, and a longer half-life in vivo compared with the human GLP-1. Uses of such compounds and compositions include treating non-insulin-dependent diabetes, insulin-dependent diabetes, and obesity.Type: ApplicationFiled: January 31, 2012Publication date: August 2, 2012Inventors: Yali Wang, Aifeng Lü, Changan Sun, Hengli Yuan
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Patent number: 8227571Abstract: The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments.Type: GrantFiled: December 11, 2008Date of Patent: July 24, 2012Assignee: Roche Palo Alto LLCInventors: Lin Chen, Yeun-Kwei Han, Christopher R. Roberts
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Patent number: 8222205Abstract: Disclosed is a method of preparing a GLP-1 compound that is soluble in aqueous solution at pH 7.4 from a GLP-1 compound that is substantially insoluble in aqueous solution at pH 7.4. The insoluble GLP-1 compound is dissolved in aqueous base or in aqueous acid to form a GLP-1 solution. The GLP-1 solution is then neutralized to a pH at which substantially no amino acid racemization of the GLP-1 compounds occurs, after which the soluble GLP-1 compound is isolated from the neutralized solution.Type: GrantFiled: September 1, 2009Date of Patent: July 17, 2012Assignee: Eli Lilly and CompanyInventors: Walter Francis Prouty, Jr., Joseph Vincent Rinella, Jr.
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Publication number: 20120178670Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes and 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: ApplicationFiled: June 24, 2010Publication date: July 12, 2012Applicant: Zealand Pharma A/SInventors: Ditte Riber, Eddi Meier, Jens Rosengren Daugaard, Marie Skovgaard, Jakob Lind Tolborg, Gita Kampen, Camilla Ærteberg Bæk
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Publication number: 20120171291Abstract: Nanoparticles having a core and a corona of ligands covalently linked to the core, wherein peptides are bound to or associated with the nanoparticles.Type: ApplicationFiled: June 10, 2011Publication date: July 5, 2012Inventors: Thomas Rademacher, Phillip Williams, Christof Bachmann, Africa Garcia Barrientos, Esther de Torres Dominguez, Javier del Campo Menoyo
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Publication number: 20120165503Abstract: Peptide analogs of oxyntomodulin (OXM, glucagon-37), which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to act as a dual GLP-1/glucagon receptor (GCGR) agonistm are described. The peptide analogs are useful for treatment of metabolic disorders such as diabetes and obesity.Type: ApplicationFiled: December 18, 2009Publication date: June 28, 2012Inventors: Paul E. Carrington, George Eiermann, Donald Marsh, Joseph Metzger, Alessandro Pocai, Ranabir Sinha Roy, Bianchi Bianchi, Paolo Ingallinella, Antonello Pessi, Alessia Santoprete, Elena Capito, Richard Dimarchi, Brian Ward
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Patent number: 8202837Abstract: The present invention relates to methods of administering hypoglycemic agents and/or GLP-1 agonists.Type: GrantFiled: November 3, 2006Date of Patent: June 19, 2012Assignee: GlaxoSmithKline LLCInventors: Mark A. Bush, Mary Colleen O'Neill
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Publication number: 20120149868Abstract: The invention relates to an effective process for purifying a peptide which has been prepared by solid phase peptide synthesis. Also encompassed by the invention is a kit comprising reagents for said process and the purified peptide obtained by said process.Type: ApplicationFiled: May 15, 2009Publication date: June 14, 2012Applicant: Novo Nordisk A/SInventors: Camilla Kornbeck, Thomas Budde Hansen
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Publication number: 20120141416Abstract: The present invention relates to multimeric (e.g., dimeric, trimeric) forms of peptide vectors that are capable of crossing the blood-brain barrier (BBB) or efficiently entering particular cell types. These multimeric peptide vectors, when conjugated to agents (e.g., therapeutic agents) are capable of transporting the agents across the BBB or into particular cell types. These compounds are therefore particularly useful in the treatment of neurological diseases.Type: ApplicationFiled: June 30, 2010Publication date: June 7, 2012Applicant: Angiochem Inc.Inventors: Michel Demeule, Christian Che, Carine Thiot
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Patent number: 8193149Abstract: The present invention is directed to the use of the peptide compound Tyr-Pro-Ile-Lys-Pro-Glu-Ala-Pro-Gly-Glu-Asp-Ala-Ser-Pro-Glu-Glu-Leu-Asn-Arg-Tyr-Tyr-Ala-Ser-Leu-Arg-His-Tyr-Leu-Asn-Leu-Val-Thr-Arg-Gln-Arg-Tyr-NH2 as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilisate or liquide buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Tyr-Pro-Ile-Lys-Pro-Glu-Ala-Pro-Gly-Glu-Asp-Ala-Ser-Pro-Glu-Glu-Leu-Asn-Arg-Tyr-Tyr-Ala-Ser-Leu-Arg-His-Tyr-Leu-Asn-Leu-Val-Thr-Arg-Gln-Arg-Tyr-NH2 optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.Type: GrantFiled: September 9, 2008Date of Patent: June 5, 2012Assignee: mondoBIOTECH Laboratories AGInventors: Dorian Bevec, Fabio Cavalli, Vera Cavalli, Gerald Bacher
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Publication number: 20120135919Abstract: A conjugate that includes a drug covalently linked to a polymer. Upon administration, the conjugate is digested by an enzyme that is present at the site of administration thereby releasing a therapeutic agent. The conjugate may demonstrate substantially the same pharmacokinetic and pharmacodynamic behavior as the drug itself. A material for controllably releasing a conjugate in response to the local concentration of a molecular indicator. The material includes a plurality of conjugates and a plurality of multivalent cross-linking agents. The polymers of the conjugates include an analog of the indicator within their covalent structure. The multivalent cross-linking agents include cross-link receptors that interact with the indicator analog and thereby cross-link the conjugates.Type: ApplicationFiled: February 6, 2012Publication date: May 31, 2012Applicant: SMARTCELLS, INC.Inventors: Thomas M. Lancaster, Matthew Nalewanski, Todd C. Zion
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Publication number: 20120129768Abstract: This invention discloses GLP-1 analogues and their pharmaceutical salts, wherein the GLP-1 analogue comprises an amino acid sequence of general formula (I), wherein Lys represents a modified lysine with a lipophilic acid. The GLP-1 analogues provided by this invention have the function of human GLP-1, and a longer half-life in vivo compared with the human GLP-1. Uses of such compounds and compositions include treating non-insulin-dependent diabetes, insulin-dependent diabetes, and obesity.Type: ApplicationFiled: July 29, 2010Publication date: May 24, 2012Inventors: Yali Wang, Aifeng Lü, Changan Sun, Hengli Yuan
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Patent number: 8183340Abstract: The invention provides GLP-1 compounds coupled to two polyethylene glycol molecule or derivative thereof, resulting in a biologically active peptide with an extended half-life and a slower clearance when compared to that of unPEGylated peptide. These PEGylated GLP-1 compounds and compositions are useful in treating conditions or disorders benefited by lowering blood glucose, decreasing food intake, decreasing gastric or intestinal emptying, increasing beta (?) cell population, or decreasing gastric or intestinal motility.Type: GrantFiled: May 11, 2006Date of Patent: May 22, 2012Assignee: Eli Lilly and CompanyInventors: Wolfgang Glaesner, John Philip Mayer, Rohn Lee Millican, Jr., Andrew Mark Vick, Lianshan Zhang
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Publication number: 20120122783Abstract: 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: ApplicationFiled: October 23, 2008Publication date: May 17, 2012Applicant: INDIANA UNIVERSITY RESEARCH AND TECHOLOGY CORPORATIONInventors: Richard D. Dimarchi, Bin Yang
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Publication number: 20120100070Abstract: 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: ApplicationFiled: April 6, 2010Publication date: April 26, 2012Applicant: Board of Regents, The University of Texas SystemInventors: Jung-Mo Ahn, Xiankai Sun
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Patent number: 8158579Abstract: The invention provides fusion proteins comprising an exendin-4 fused to a transferrin (Tf) via a polypeptide linker, as well as corresponding nucleic acid molecules, vectors, host cells, and pharmaceutical compositions. The invention also provides the use of the exendin-4/Tf fusion proteins for treatment of Type II diabetes, obesity, and to reduce body weight.Type: GrantFiled: November 30, 2010Date of Patent: April 17, 2012Assignee: BioRexis Pharmaceutical CorporationInventors: David James Ballance, Christopher P. Prior, Homayoun Sadeghi, Andrew J. Turner
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Publication number: 20120088716Abstract: Method for increasing half-life of compounds in plasma and novel derivatives of such compounds.Type: ApplicationFiled: December 15, 2011Publication date: April 12, 2012Applicant: Novo Nordisk A/SInventors: Florencio Zaragoza Dörwald, Christine Bruun Schiødt, Thomas Kruse Hansen, Kjeld Madsen
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Patent number: 8138305Abstract: The present invention is directed to peptide analogues of glucagon-like peptide-1, the pharmaceutically-acceptable salts thereof, to methods of using such analogues to treat mammals and to pharmaceutical compositions useful therefore comprising said analogues.Type: GrantFiled: July 20, 2007Date of Patent: March 20, 2012Assignee: Ipsen Pharma S.A.S.Inventor: Zheng Xin Dong
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Publication number: 20120059145Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an ?-helical moiety, or one or more proline residues.Type: ApplicationFiled: August 31, 2011Publication date: March 8, 2012Applicant: University of Georgia Research Foundation, Inc.Inventor: Elliot ALTMAN
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Publication number: 20120046222Abstract: The disclosure provides N-terminus conformationally constrained compounds, which may comprise peptide mimetics and/or amino acid substitutions, which may be used in peptides, such as GLP-1 receptor agonist compounds, to induce a ?-turn secondary structure at the N-terminus. The N-terminus conformationally constrained compounds may be used for research purposes; to produce GLP-1 receptor agonist compounds having improved GLP-1 receptor binding activity, enzymatic stability, or in vivo glucose lowering activity; and to develop GLP-1 receptor agonist compounds which have fewer amino acid residues. The disclosure also provides GLP-1 receptor agonist compounds, such as exendins, exendin analogs, GLP-1 (7-37), GLP-1 (7-37) analogs, comprising the N-terminus conformationally constrained compounds. The compounds are useful for treating various diseases, such as diabetes and obesity. The disclosure also provides methods for chemically synthesizing the N-terminus conformationally constrained compounds.Type: ApplicationFiled: March 26, 2010Publication date: February 23, 2012Applicant: Amylin Pharmaceuticals, Inc.Inventors: Josue Alfaro-Lopez, Abhinandini Sharma, Soumitra S. Ghosh