Solution Phase Synthesis Patents (Class 530/338)
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Publication number: 20090023641Abstract: The present invention relates to cyclic cationic peptides and their use in the treatment of microbial infections.Type: ApplicationFiled: December 21, 2006Publication date: January 22, 2009Inventor: Deborah O'Neil
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Publication number: 20080281075Abstract: The present invention provides a process comprising substitution of an acceptor molecule comprising a group —XC(O)— wherein X is O, S or NR8, where R8 is C1-6 alkyl, C6-12 aryl or hydrogen, with a nucleophile, wherein the acceptor molecule is cyclised such that said nucleophilic substitution at —XC(O)— occurs without racemisation. This process has particular application for the production of a peptide by extension from the activated carboxy-terminus of an acyl amino acid residue without epimerisation.Type: ApplicationFiled: March 20, 2008Publication date: November 13, 2008Inventors: Laurence M. Harwood, Ran Yan
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Patent number: 7449547Abstract: A process for the total synthesis of Distamycin, and synthetic poly-(4 aminopyrrole-2-carboxamide) congeners thereof, using 1-methyl-4-forinylamino-2-pyrrolecarbonyl chloride iteratively as an intermediate, is provided. The process finds application for both in solution and solid support synthetic technologies.Type: GrantFiled: May 28, 2004Date of Patent: November 11, 2008Assignee: Naxopharma S.r.l.Inventor: Paolo Lombardi
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Patent number: 7435791Abstract: The present invention relates to a process for rapid solution synthesis of a peptide, the process comprising repetitive cycles of steps (a)-(d): (a) a coupling step, using an excess of an activated carboxylic component to acylate an amino component, (b) a quenching step in which a scavenger is used to remove residual activated carboxylic functions, wherein the scavenger may also be used for deprotection of the growing peptide, (c) one or more aqueous extractions and optionally, (d) a separate deprotection step, followed by one or more aqueous extractions, characterised in that the process comprises at least one step (b), referred to as step (b?), in which an amine or a thiol comprising a free anion or a latent anion is used as a scavenger of residual activated carboxylic functions. During the process of this invention the growing peptide need not be isolated until the final peptide sequence has been obtained.Type: GrantFiled: October 23, 2003Date of Patent: October 14, 2008Assignee: N.V. OrganonInventors: Ivo Franci Eggen, Paulus Bernardus Wilhelmus Ten Kortenaar, Cornelis Albert Gruson Haasnoot
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Patent number: 7427678Abstract: This invention discloses a novel method for immobilizing molecules to a support. Specifically, this invention discloses a method of immobilizing derivatized biomolecules, such as oligonucleotides, using cycloaddition reactions, such as the Diels-Alder reaction. Included in this invention are the novel immobilized biomolecules that can be prepared according to the method of this invention.Type: GrantFiled: May 1, 2001Date of Patent: September 23, 2008Assignee: Sigma-Aldrich Co.Inventors: Wolfgang Pieken, Andreas Wolter, David P. Sebesta, Michael Leuck, Hallie A. Latham-Timmons, John Pilon, Gregory M. Husar
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Publication number: 20080207487Abstract: The present invention provides a manufacturing method for polypeptides that are produced in insect cells using a baculoviral expression system. In one example, the insect cell culture is supplemented with a lipid mixture immediately prior to infection (e.g., one hour prior to infection). The polypeptides are isolated from the insect cell culture using a method that employs anion exchange or mixed-mode chromatography early in the purification process. This process step is useful to remove insect-cell derived endoglycanases and proteases and thus reduces the loss of desired polypeptide due to enzymatic degradation. In another example, mixed-mode chromatography is combined with dye-ligand affinity chromatography in a continuous-flow manner to allow for rapid processing of the insect-cell culture liquid and capture of the polypeptide.Type: ApplicationFiled: November 2, 2007Publication date: August 28, 2008Applicant: Neose Technologies, Inc.Inventors: Shawn DeFrees, Kyle Kinealy, Sibylle Herzer
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Patent number: 7396903Abstract: A preferred way of converting insulin precursors into insulin compounds is to perform an enzymatic peptide cleavage in an aqueous medium and, thereafter, without removal of the intermediate product formed, to add an amino acid ester or a peptide ester and an organic solvent so that the desired coupling takes place.Type: GrantFiled: November 19, 2002Date of Patent: July 8, 2008Assignee: Novo Nordisk A/SInventors: Are Bogsnes, Ingun Christensen, Per Balschmidt
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Patent number: 7381408Abstract: The invention provides methods of chemically synthesizing chimeric proteins comprising at least a portion of an immunoglobulin constant region and a biologically active molecule.Type: GrantFiled: May 6, 2004Date of Patent: June 3, 2008Assignee: Syntonix Pharmaceuticals, Inc.Inventors: Adam R. Mezo, Robert T. Peters
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Patent number: 7329727Abstract: Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.Type: GrantFiled: November 14, 2003Date of Patent: February 12, 2008Assignee: The Regents of the University of CaliforniaInventor: Timothy J. Deming
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Patent number: 7268210Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.Type: GrantFiled: May 24, 2005Date of Patent: September 11, 2007Assignee: Applied Research Systems ARS Holding N.V.Inventors: Nabil El-Tayar, Xuan Zhao, Michael D. Bentley
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Patent number: 7214768Abstract: This invention relates to an improved process for the minimization of acid-catalyzed reactions of certain echinocandins of the kind disclosed in U.S. Pat. No. 5,378,804. The process involves the use of a boronic acid.Type: GrantFiled: April 8, 2002Date of Patent: May 8, 2007Assignee: Merck & Co., Inc.Inventors: Kevin M. Belyk, William R. Leonard
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Patent number: 7192713Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.Type: GrantFiled: May 18, 2000Date of Patent: March 20, 2007Assignee: President and Fellows of Harvard CollegeInventors: Gregory L. Verdine, Christian E. Schafmeister
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Patent number: 7084250Abstract: The present invention relates to a process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides of the formula I, in which the anions X are physiologically acceptable anions, and their analogs, which are effective inhibitors of the blood coagulation factor Xa and which can be used, for example, for preventing thromboses. The process according to the invention comprises the coupling of 2-[2-acetylamino-3-(4-amidinophenyl)propionylamino]-2-cyclohexylacetic acid, which is obtained from 2-[2-acetylamino-3-(4-cyanophenyl)acryloylamino]-2-cyclohexylacetic acid by asymmetric hydrogenation and conversion of the cyano group into the amidine, or a salt thereof, with a 3-(2-amino-2-carbamoylethyl)-1-methylpyridinium salt or a salt thereof. The invention furthermore provides starting materials and intermediates for this process, processes for their preparation and acetyl-(S)-4-amidiniophenylalanyl-(S)-cyclohexylglycyl-(S)-(1-methyl-3-pyridinio)alaninamide as ditosylate salt.Type: GrantFiled: June 17, 2004Date of Patent: August 1, 2006Assignee: Sanofi-Aventis Deutschland GmbHInventors: Gerhard Breipohl, Wolfgang Holla, Heiner Jendralla, Gerhard Beck
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Patent number: 7053055Abstract: Novel compounds of unstable inhibitors of the serine peptidase dipeptidyl peptidase IV, are used in the treatment of various disorders, especially of metabolic disorders. The compounds can be used in the treatment of impaired glucose tolerance, glucosuria, hyperlipidaemia, metabolic acidoses, diabetes mellitus, diabetic neuropathy and nephropathy.Type: GrantFiled: December 21, 2000Date of Patent: May 30, 2006Assignee: Prosidion Ltd.Inventors: Hans-Ulrich Demuth, Jorn Schmidt, Torsten Hoffmann, Konrad Glund
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Patent number: 6982315Abstract: The invention relates to a process for the preparation of carboxamides, in particular peptides, from an acid component in the form of a compound containing at least one carboxyl group and an amine component in the form of a compound containing at least one primary or secondary amino group, and its use.Type: GrantFiled: March 27, 2002Date of Patent: January 3, 2006Assignee: Bayer AktiengesellschaftInventors: Joachim Rudolph, Günther Jung, Bernd Thern
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Patent number: 6962902Abstract: This invention relates generally to dipeptides and tripeptides and to methods for pharmaceutical treatment of mammals using analogs of such dipeptides and tripeptides. More specifically, the invention relates to tripeptides and their analogs, to pharmaceutical compositions containing such dipeptides and tripeptides and to methods of treatment of mammals using such dipeptides and tripeptides. In addition, the invention relates to methods of treatment of mammals using such dipeptides and tripeptides for control of appetite, blood pressure, cardiovascular response, libido, and circadian rhythm.Type: GrantFiled: May 18, 2004Date of Patent: November 8, 2005Assignee: University of CincinnatiInventors: Ambikaipakan Balasubramanium, William T. Chance
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Patent number: 6939946Abstract: A method for modifying the cyclic peptide ring system of Echinocandin-type compounds to produce new analogs having antifungal activity is provided. The inventive process comprises opening the cyclic peptide ring, cleaving the terminal ornithine unit, inserting at least one new amino acid or other synthetic unit and closing the ring to produce a new cyclic peptide ring structure. The process allows one to incorporate features such as water-solubility into the cyclic peptide ring nucleus, sites for further modification, increase or decrease the number of amino acid or peptide units within the ring nucleus, and increase or decrease the total number of members within the ring. The invention further provides novel Echinocandin type compounds and their use as antifungal or anti-parasitic agents.Type: GrantFiled: September 30, 2003Date of Patent: September 6, 2005Assignee: Eli Lilly and CompanyInventors: Peter Stanley Borromeo, Jeffrey Daniel Cohen, George Stuart Gregory, Stacy Kay Henle, Stephen Andrew Hitchcock, Louis Nickolaus Jungheim, Daniel Ray Mayhugh, Timothy Alan Shepherd, William Wilson Turner, Jr.
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Patent number: 6914121Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog either directly or via a bifunctional linker molecule, such as an amino acid, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.Type: GrantFiled: June 28, 2002Date of Patent: July 5, 2005Assignee: Applied Research Systems Ars Holding N.V.Inventors: Nabil El-Tayar, Xuan Zhao, Michael D. Bentley
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Patent number: 6897289Abstract: A procedure for the solid phase peptide synthesis (SPPS), following a linear or convergent strategy, wherein the peptides contain the sequence of general formula (I), wherein n, Y, X and A1 to An have the meanings indicated in the specification. Said procedure comprises: the use of amino acids with the N? group protected, protecting the side chains of those amino acids that have their side chain alkylated or acylated in the final product with labile protecting groups, protecting the side chains of at least one of the amino acids that has its chain free in the final product with hyperlabile products and using a polymeric support which provides labile peptide-resin bonds. Said procedure is valid for the synthesis of gosereline and busereline Y—A1—A2—A3— . . . A(n-1)—An—X.Type: GrantFiled: May 5, 2000Date of Patent: May 24, 2005Assignee: Lipotec, S.A.Inventors: Berta Ponsati I Obiols, Marc Canas I Poblet, Gemma Jodas I Farres, Javier Clemente Rodriguez, Jordi Barcadit I Cabado
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Patent number: 6878557Abstract: A method for constructing an array of synthetic molecular constructs, by forming a plurality of molecular constructs having a scaffold backbone of a chemical molecule comprising a linear, branched or cyclic organic compound having at least atoms of carbon, nitrogen, sulfur, phosphorus, or combinations thereof, and at least one location on the molecule capable of undergoing reaction with other molecules for attachment of at least one structural diversity element; laying out an array possessing a logical ordering of sub-arrays of the molecular constructs; providing each sub-array with molecular constructs having the scaffold backbone and at least one structural diversity element which is different from the others; and relating each sub-array within the array to all other sub arrays by the difference in the structural diversity elements.Type: GrantFiled: January 20, 1998Date of Patent: April 12, 2005Assignee: ArQule, Inc.Inventors: Robert Zambias, David A. Bolten, Joseph C. Hogan, Paul Furth, David Casebier, Cheng Tu
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Patent number: 6864357Abstract: The present invention relates to a process for the preparation of peptides using an excess of an activated carboxylic component to acylate an amino component, wherein after the acylation an amine comprising a free anion or a latent anion is used as a scavenger of residual activated carboxylic functions. This process is useful for the preparation of oligo- and polypeptides and, more generally, in the preparation of compounds containing one or more amide bonds.Type: GrantFiled: July 19, 2002Date of Patent: March 8, 2005Assignee: Akzo Nobel N.V.Inventors: Ivo Franci Eggen, Paulus Bernardus Wilhelmus Ten Kortenaar
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Patent number: 6849710Abstract: A fragment condensation process for the synthesis of analogs of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP), in which amino acid residues (22-31) form a synthetic amphipathic ?-helix, is provided.Type: GrantFiled: July 30, 1997Date of Patent: February 1, 2005Assignee: F. Hoffmann-La Roche AGInventor: Humberto Arzeno
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Patent number: 6822074Abstract: Process for the preparation of the cyclic pentapeptide cyclo(Arg-Gly-Asp-DPhe-NMeVal) by cyclization of a linear pentapeptide selected from the group consisting of H-Arg(Pbf)-Gly-Asp(OBzl)-DPhe-NMeVal-OH, H-Gly-Asp(OBzl)-DPhe-NMeVal-Arg(Pbf)-OH, H-Asp(OBzl)-DPhe-NMeVal-Arg(Pbf)-Gly-OH, H-DPhe-NMeVal-Arg(Pbf)-Gly-Asp(OBzl)-OH or H-NMeVal-Arg(Pbf)-Gly-Asp (OBzl)-DPhe-OH, subsequent protective group removal and, if appropriate, further conversion into its physiologically acceptable salts.Type: GrantFiled: September 12, 2001Date of Patent: November 23, 2004Assignee: Merck Patent GmbHInventors: Alfred Jonczyk, Markus Arnold
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Patent number: 6762281Abstract: Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.Type: GrantFiled: September 7, 2001Date of Patent: July 13, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Andrei P. Guzaev
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Patent number: 6750312Abstract: A method for preparing a solid support material for carrying out a chemical reaction, said method comprising the following steps: (i) reacting an amino functionalised solid material with a carboxylic acid having at least two similarly protected amino groups to form amide bonds between them, (ii) removing protecting groups in a single step, (iii) optionally repeating steps (i) and (ii) one or more times using the product of the preceding step as the amino functionalised solid material, and (iv) connecting a linkage agent to at least some of the free NH2 groups of the product. The method increases the loading capacity of the solid support material. It is particularly useful in connection with peptide synthesis.Type: GrantFiled: March 26, 2002Date of Patent: June 15, 2004Assignee: Avecia LimitedInventors: Craig Stephen Harris, Donald Alfred Wellings, Francis Joseph Montgomery, Richard John Brown
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Patent number: 6686445Abstract: A composition of matter, denominated herein as 12a-r, having the structural formula set forth below: wherein R is selected from the group consisting of: a) R=NHPh; b) R=NHCH2Ph; c) R=NH(CH2)2Ph; d) R=NH(CH2)2‘-4-F-Ph; e) R=NH(CH2)2-4-Cl-Ph; f) R=NH(CH2)2-3-Cl-Ph; g) R=NH(CH2)2-2-Cl-Ph; h) R=NH(CH2)2-4-Br-Ph; i) R=NH(CH2)2-4-NO2-Ph; j) R=NH(CH2)2-3,4-(CH3O)2Ph; k) R=NH(CH2)2-2-pyridine; l) R=NH(CH2)3Ph; m) R=L-Phe-OCH3; n) R=L-Met-OCH3; o) R=L-Pro-OCH3; p) R=NH-2-thiazolyl; q) R=NH-2-benzothiazolyl; r) R=NH-3-quinolyl; and methods of making these compounds 12a-r.Type: GrantFiled: March 21, 2000Date of Patent: February 3, 2004Assignee: Arizona Board of Regents, acting for and on behalf of Arizona State UniversityInventors: George R. Pettit, Erik J. Flahive
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Patent number: 6686446Abstract: Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.Type: GrantFiled: June 8, 2001Date of Patent: February 3, 2004Assignee: The Regents of the University of CaliforniaInventors: Timothy J. Deming, Miaoer Yu, Scott A. Curtin, Jungyeon Hwang, Michael D. Wyrsta, Andrew Nowak, Scott W. Seidel
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Patent number: 6680365Abstract: Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for making block copolypeptides and related protocols for adding aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains by exposing the NCA to solutions containing polyaminoacid chains having an amido amidate metallacyle end groups and reacting the NCA with the amido containing metallacyle end group so that the NCA is added to the polyaminoacid chain. Addition methods include means of controlling the addition of aminoacid-N-carboxyanhydrides to polyaminoacid chains by reacting NCAs with initiator molecules and allowing initiator complexes to open the ring of the NCAs through oxidative addition across either the O—C5 or O—C2 anhydride bond resulting a controlled polypeptide polymerization. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.Type: GrantFiled: March 19, 1999Date of Patent: January 20, 2004Assignee: The Regents of the University of CaliforniaInventor: Timothy J. Deming
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Patent number: 6664372Abstract: Peptidomimetic azatides and combinatorial oligoazitide libraries are produced by means of a stepwise synthesis. Combinatorial library construction of this new biomimetic polymer provides a means to fabricate global peptidomimetic libraries.Type: GrantFiled: September 1, 1998Date of Patent: December 16, 2003Assignee: The Scripps Research InstituteInventors: Kim D. Janda, Hyunsoo Han
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Patent number: 6653281Abstract: A method for modifying the cyclic peptide ring system of Echinocandin-type compounds to produce new analogs having antifungal activity is provided. The inventive process comprises opening the cyclic peptide ring, cleaving the terminal omithine unit, inserting at least one new amino acid or other synthetic unit and closing the ring to produce a new cyclic peptide ring structure. The process allows one to incorporate features such as water-solubility into the cyclic peptide ring nucleus, sites for further modification, increase or decrease the number of amino acid or peptide units within the ring nucleus, and increase or decrease the total number of members within the ring. The invention further provides novel Echinocandin type compounds and their use as antifungal or anti-parasitic agents.Type: GrantFiled: May 24, 2001Date of Patent: November 25, 2003Assignee: Eli Lilly and CompanyInventors: Peter Stanley Borromeo, Jeffrey Daniel Cohen, George Stuart Gregory, Stacy Kay Henle, Stephen Andrew Hitchcock, Louis Nickolaus Jungheim, Daniel Ray Mayhugh, Timothy Alan Shepherd, William Wilson Turner, Jr.
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Patent number: 6632922Abstract: Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for making self assembling amphiphilic block copolypeptides and related protocols adding oligo(ethyleneglycol) functionalized aninoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex, thereby forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.Type: GrantFiled: May 10, 2000Date of Patent: October 14, 2003Assignee: The Regents of the University of CaliforniaInventors: Timothy J. Deming, Miaoer Yu, Scott A. Curtin, Jungyeon Hwang, Michael D. Wyrsta
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Patent number: 6610655Abstract: Cyclic pentapeptides are disclosed having the following formula (I)-Cyclo(-A1-A2-A3-A4-A5-)-wherein A1, A2, A3, A4 and A5 are amino acid residues. The pentapeptide has amino acid residues in positions 1-2-3 to form a &ggr;-turn, and amino acid residues in positions 3-4-5-1 to form a &bgr;-turn in combination with the &ggr;-turn. D-&agr;-amino acid residues are selected for A1, A3, and A5 and L-&agr;-amino acid residues are selected for A2 and A4. Compounds having &ggr;-turns and &bgr;-turns can be synthesized, regardless of the kinds of amino acid residues, and it is possible to synthesize compounds in which desired amino acid residues are introduced into sites of &bgr;-turn and &ggr;-turn based on their importance from the viewpoint of biological activity. The present invention is therefore available for design of compounds having biological activity.Type: GrantFiled: November 15, 2001Date of Patent: August 26, 2003Assignee: Takeda Chemical Industries, Inc.Inventors: Mitsuhiro Wakimasu, Hiroshi Inooka, Satoshi Endo, Takashi Kikuchi
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Patent number: 6608175Abstract: Certain substituted oxadiazole, thiadiazole and triazole peptoids which are useful as inhibitors of serine proteases, are prepared in various embodiments using Grignard reagents and alkyllithium reagents and various aldehydes to make oxadiazole, thiadiazole and triazole peptoid alcohols, which are then oxidized to the desired keto products.Type: GrantFiled: November 16, 2001Date of Patent: August 19, 2003Assignee: Cortech, Inc.Inventors: Albert Gyorkos, Lyle W. Spruce
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Patent number: 6596867Abstract: This application relates to processes for making compounds of formula I, and processes for making intermediates useful in the processes for making compounds of formula I.Type: GrantFiled: December 11, 2000Date of Patent: July 22, 2003Assignee: Pfizer Inc.Inventors: Philip Albert Carpino, Paul Andrew Dasilva-Jardine, Bruce Allen Lefker, Jerry Anthony Murry
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Patent number: 6566329Abstract: A readily-soluble freeze-dried solid preparation of hGH with a minimal content of degradation products in terms of deamidation, dimers, polymers, and sulphoxide forms, obtainable by a method comprising a single lyophilization of an aqueous slurry of an amorphous hGH isoprecipitate, the slurry having a pH of from about 4.7 to 5.0 and being essentially free of buffer components other than acetate.Type: GrantFiled: June 14, 2000Date of Patent: May 20, 2003Assignee: Novo Nordisk A/SInventors: Giorgio Meyn, Hans Holmegaard Sørensen, Thorkild Christensen
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Patent number: 6562944Abstract: Disclosed is an improved method for preparing an activated carboxylic acid in the form of a pentafluorophenyl ester, an improved method for making a carboxamide from a pentaflourophenyl ester, and a carboxamide and carboxamide library prepared using both of these methods.Type: GrantFiled: March 22, 2000Date of Patent: May 13, 2003Assignee: Lexicon PharmaceuticalsInventors: Hartmuth C. Kolb, Qun Sun
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Patent number: 6559279Abstract: Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.Type: GrantFiled: September 8, 2000Date of Patent: May 6, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Andrei P. Guzaev
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Patent number: 6552166Abstract: The present invention is directed to the improved synthesis of compounds of formula I: which may be useful in the treatment of prostate cancer. Such compounds are synthesized in the presence of a carboxyl activating agent, an additive and a base for the preparation of a PSA conjugate which comprises an anthracycline antibiotic and an oligopeptide.Type: GrantFiled: October 18, 2000Date of Patent: April 22, 2003Assignee: Merck & Co., Inc.Inventors: Joseph E. Lynch, Michael A. Robbins, Yao-Jun Shi, David R. Lieberman
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Patent number: 6534627Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: or the acid fluoride salts thereof wherein BLK is an N-amino protecting group; AA is an amino acid residue; and X is absent or a protecting group. The amino acid fluoride is useful as a coupling agent in peptide synthesis.Type: GrantFiled: February 23, 1999Date of Patent: March 18, 2003Assignee: Research Corporation Tecnologies, Inc.Inventors: Louis A. Carpino, Ayman Ahmed El-Faham
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Patent number: 6528485Abstract: Described are various human growth hormone releasing factor-PEG conjugates as well as their pharmaceutical use.Type: GrantFiled: June 5, 2000Date of Patent: March 4, 2003Assignee: Applied Research Systems ARS Holding N.V.Inventors: Francesco Maria Veronese, Paolo Caliceti, Oddone Schiavon
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Patent number: 6521744Abstract: Nucleic acid analogs provide a particularly useful tool for the preparation of complex polymeric structures of defined geometry because they are relatively stable to reaction conditions for the preparation of such structures and provide the opportunity to induce reactive groups which would not be possible with usual nucleic acids.Type: GrantFiled: September 7, 2000Date of Patent: February 18, 2003Assignee: PNA Diagnostics A/SInventors: Hans-Georg Batz, Troels Koch, Henrik Frydenlund Hansen
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Publication number: 20030018164Abstract: The present invention relates to a process for rapid solution synthesis of a peptide, the process comprising repetitive cycles of steps (a)-(d):Type: ApplicationFiled: July 19, 2002Publication date: January 23, 2003Inventors: Ivo Franci Eggen, Paulus Bernardus Wilhelmus Ten Kortenaar, Cornelis Albert Gruson Haasnoot
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Patent number: 6506577Abstract: The synthesis of moisture-resistant adhesive polypeptides, conditions for their use, and conditions for controlling characteristics of the crosslinked matrix are disclosed. By specifically manipulating the conditions under which these networks are formed, the characteristics of the networks may be precisely regulated. These manipulatable adhesive networks are water-based, show exceptional bonding capabilities toward wet materials (including biological tissues), and have a variety of biotechnological applications.Type: GrantFiled: March 19, 1999Date of Patent: January 14, 2003Assignee: The Regents of the University of CaliforniaInventors: Timothy J. Deming, Miaoer Yu
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Patent number: 6492491Abstract: The invention relates to novel peptides synthesized according a method utilizing the hypusine reagent: wherein: Q1 Q2 and Q3 may be the same or different and are amino protective groups, provided that Q3 is orthogonal to Q1 and Q2; and Z is a hydroxy protective group, as well as improved methods of peptide synthesis wherein the above-described hypusine reagent is employed to prepare novel hypusine-containing peptides.Type: GrantFiled: March 6, 2000Date of Patent: December 10, 2002Assignee: University of Florida Research FoundationInventor: Raymond J. Bergeron, Jr.
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Patent number: 6451972Abstract: Compounds of formula (I) where n is the number 0, 1 or 2, processes for the preparation together with methods for treating pathologies related to an altered &agr;v&bgr;3 integrin-mediated cell attachment, in particular where inhibition of angiogenesis is desired, for example in tumors, also associated with metastasis.Type: GrantFiled: February 6, 2001Date of Patent: September 17, 2002Assignee: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.Inventors: Carlo Scolastico, Giuseppe Giannini
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Patent number: 6433135Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog either directly or via a bifunctional linker molecule, such as an amino acid, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.Type: GrantFiled: October 30, 2000Date of Patent: August 13, 2002Assignee: Applied Research Systems ARS Holding N.V.Inventors: Nabil El-Tayar, Xuan Zhao, Michael D. Bentley
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Publication number: 20020058788Abstract: The present invention provides a method for deprotecting a Fmoc protected amino group, said method comprising treating in a suitable medium the protected amino group with a base in the presence of a thiol compound to yield a deprotected amino group.Type: ApplicationFiled: August 24, 2001Publication date: May 16, 2002Inventor: James E. Sheppeck
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Patent number: 6380358Abstract: Trisubstituted N-protected guanidines and methods for use as guanidinylating reagents to yield N-protected guanidine derivatives.Type: GrantFiled: December 1, 1999Date of Patent: April 30, 2002Assignee: The Regents of the University of CaliforniaInventors: Murray Goodman, Konrad Feichtinger, Todd T. Romoff
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Patent number: RE37686Abstract: This invention relates to a process for forming an amide or an ester from a reaction between an amine or an alcohol, respectively and an acylating derivative of a carboxylic acid, in the presence of an effective amount of a compound having the formula: and N-oxides thereof and salts thereof.Type: GrantFiled: December 3, 1998Date of Patent: April 30, 2002Assignee: Research Corporation Technologies, Inc.Inventor: Louis A. Carpino
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Patent number: RE38073Abstract: This invention relates to a process for forming an amide or an ester from a reaction between an amine or an alcohol, respectively and an acylating derivative of a carboxylic acid, in the presence of an effective amount of a compound having the formula: and N-oxides thereof and salts thereof.Type: GrantFiled: June 30, 1999Date of Patent: April 8, 2003Assignee: Research Corporations Technologies, Inc.Inventor: Louis A. Carpino