Phosphorus Containing Patents (Class 514/51)
  • Patent number: 7132410
    Abstract: The present invention are directed to P1, P4-di(uridine 5?-)tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?-)tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?-)tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.
    Type: Grant
    Filed: February 9, 2005
    Date of Patent: November 7, 2006
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, Edward G. Brown
  • Patent number: 7119110
    Abstract: A method for preventing and or reducing the symptoms of insulin resistance and a related syndrome in persons comprises identifying persons having or at risk for having such symptoms, and administering to them an effective amount of a composition comprising niacin-bound chromium that prevents or reduces the symptoms. Compositions incorporating niacin-bound chromium and additional compounds also are disclosed that are particularly effective in synergistically preventing or reducing these symptoms.
    Type: Grant
    Filed: October 4, 2002
    Date of Patent: October 10, 2006
    Assignee: Interhealth Nutraceuticals Incorporated
    Inventors: Debasis Bagchi, Harry G. Preuss, Shil C. Kothari
  • Patent number: 7115585
    Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides.
    Type: Grant
    Filed: February 27, 2002
    Date of Patent: October 3, 2006
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, James G. Douglass, III, Sammy Ray Shaver, Ward M. Peterson, Edward G. Brown, Christopher S. Crean
  • Patent number: 7115584
    Abstract: The present invention discloses a method for treating HIV that includes administering ?-D-D4FC or its pharmaceutically acceptable salt or prodrug to a human in need of therapy in combination or alternation with a drug that induces a mutation in HIV-1 at a location other than the 70(K to N), 90 or the 172 codons of the reverse transcriptase region. Also disclosed is a method for using ?-D-D4FC as “salvage therapy” to patients which exhibit drug resistance to other anti-HIV agents. ?-D-D4FC can be used generally as salvage therapy for any patient which exhibits resistance to a drug that induces a mutation at other than the 70(K to N), 90 or the 172 codons.
    Type: Grant
    Filed: January 23, 2003
    Date of Patent: October 3, 2006
    Assignee: Emory University
    Inventors: Raymond F. Schinazi, Jennifer L. Hammond, John W. Mellors, Dennis C. Liotta
  • Patent number: 7101860
    Abstract: This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutically effective amount of P2Y12 receptor antagonist compound, wherein said amount is effective to bind the P2Y12 receptors on platelets and inhibit ADP-induced platelet aggregation. The P2Y12 receptor antagonist compounds useful for this invention include mononucleoside polyphosphates and dinucleoside polyphosphates of general Formula I, or salts thereof The present invention also provides compositions comprising mononucleoside polyphosphates and dinucleoside polyphosphates according to Formula Ia and Ib.
    Type: Grant
    Filed: August 21, 2001
    Date of Patent: September 5, 2006
    Assignees: Inspire Pharmaceuticals, Inc., University of North Carolina
    Inventors: Jose L. Boyer, Gillian M. Olins, Benjamin R. Yerxa, James G. Douglass
  • Patent number: 7094770
    Abstract: The present invention relates to a composition for and a method of treating hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, hepatitis D virus (HDV) infection or a proliferative disorder in a patient using an effective amount of a compound selected from the group consisting of formulas [I]–[IV] below and mixtures of two or more thereof: wherein the substituents are as defined herein. Pharmaceutical compositions comprising these compounds in combination with other HBV, HCV, or HDV agents is also disclosed.
    Type: Grant
    Filed: April 13, 2001
    Date of Patent: August 22, 2006
    Assignee: Pharmasset, Ltd.
    Inventors: Kyoichi A. Watanabe, S. Balakrishna Pai
  • Patent number: 7091190
    Abstract: The present invention is related to antiviral compositions comprising long-chain aliphatic compounds in combination with a nucleoside analog or phosphonoformic acid, in a pharmaceutically acceptable carrier. Methods for treating viral infections using such compositions are also disclosed.
    Type: Grant
    Filed: July 16, 2002
    Date of Patent: August 15, 2006
    Assignee: Avanir Pharmaceuticals
    Inventors: John F. Marcelletti, Laura E. Pope, Mohammed H. Khalil, David H. Katz, Lee R. Katz
  • Patent number: 7084128
    Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.
    Type: Grant
    Filed: January 15, 2003
    Date of Patent: August 1, 2006
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, Robert Plourde, Jr., Edward G. Brown, Ward M. Peterson
  • Patent number: 7078391
    Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.
    Type: Grant
    Filed: October 8, 2003
    Date of Patent: July 18, 2006
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Ward M. Peterson, Benjamin R. Yerxa
  • Patent number: 7074773
    Abstract: The present invention relates to an agent for the prophylaxis or treatment of diabetic neuropathy, which contains cytidine 5?-diphosphocholine (CDP-choline) as an active ingredient. The agent for the prophylaxis or treatment of diabetic neuropathy of the present invention is effective for neuropathy mainly caused by metabolic disturbance of carbohydrate and is also superior in safety. Neuropathy includes peripheral neuropathy and dysautonomia. CDP-choline is effective even by oral administration.
    Type: Grant
    Filed: April 5, 2005
    Date of Patent: July 11, 2006
    Assignee: Yamasa Corporation
    Inventors: Kazuki Endo, Toichi Abiru, Junzo Kamei
  • Patent number: 7056894
    Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.
    Type: Grant
    Filed: January 4, 2002
    Date of Patent: June 6, 2006
    Assignee: Albert Einstein College of Medicine of Yeshiva University
    Inventors: Anthony A. Sauve, Vern L. Schramm
  • Patent number: 7053064
    Abstract: The invention provides methods for treating or suppressing tobacco or nicotine usage or dependence involving administration of a therapeutically-effective amount of a cytosine-containing or cytidine-containing compound, creatine-containing compound, adenosine-containing, or adenosine-elevating compound to a mammal.
    Type: Grant
    Filed: November 6, 2003
    Date of Patent: May 30, 2006
    Assignee: The McLean Hospital Corporation
    Inventor: Scott Lukas
  • Patent number: 7022680
    Abstract: The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.
    Type: Grant
    Filed: May 30, 2002
    Date of Patent: April 4, 2006
    Assignee: Albert Einstein College of Medicine of Yeshiva University
    Inventors: Anthony A. Sauvé, Vern L. Schramm
  • Patent number: 7018985
    Abstract: The present invention provides novel compounds of dinucleotide polyphosphates and the method of preventing or treating diseases or conditions associated with platelet aggregation. The method comprises administering systemically to a patient a pharmaceutical comprising a purinergic P2? receptor antagonist, in an amount effective to elevate its extracellular concentration to bind to P2? receptors and inhibit P2? receptor-mediated platelet aggregation. Methods of systemic administration include injection by intravenous, intramuscular, intrasternal and intravitreal routes, infusion, transdermal administration, oral administration, rectal administration and intra-operative instillation.
    Type: Grant
    Filed: August 21, 2000
    Date of Patent: March 28, 2006
    Assignees: Inspire Pharmaceuticals, Inc., University of North Carolina at Chapel Hill
    Inventors: José L. Boyer, Gillian M. Olins, Benjamin R. Yerxa, James G. Douglass, III
  • Patent number: 6995145
    Abstract: The invention provides methods and compositions for modulating the activity of therapeutic agents for the treatment of a cancer by administering one or more agents that (either alone or in combination) induces telomere damage and inhibits telomerase activity in the cancer cell. The method initially uses, e.g., a telomere damage-inducing agent such as paclitaxel, and a telomerase inhibitory agent such as AZT. The invention also provides methods for identifying other agents with telomere damage-inducing activity and/or telomerase inhibitory activity (as well as and compositions having such activity), for use in the treatment of cancer.
    Type: Grant
    Filed: June 5, 2000
    Date of Patent: February 7, 2006
    Inventors: Jessie L.-S. Au, M. Guillaume Wientjes
  • Patent number: 6989376
    Abstract: Methods of treating certain neurological diseases using exogenous uridine or a uridine source alone as a precursor of endogenous cytidine, particularly in the human brain, are disclosed. Methods are also disclosed wherein exogenous uridine or a uridine source is combined either with drugs increasing uridine availability or with compounds that serve as a source of choline in phospholipid synthesis.
    Type: Grant
    Filed: July 30, 1999
    Date of Patent: January 24, 2006
    Assignee: Massachusetts Institute of Technology
    Inventors: Carol Watkins, Richard J. Wurtman
  • Patent number: 6987095
    Abstract: The present invention provides for the improved uptake of feed additives, pigments for use in coloring the flesh and the like. This improved intestinal uptake of foodstuffs and additives is effected through enhancing the development of the intestinal tract. Specifically the present method comprises of feeding fish with a diet which has an augmented level of nucleotides present therein. The nucleotides may be selected from the group consisting of nucleotides of uridine, guanosine, cytidine, thymindine, adenosine and mixtures thereof. The resultant improvement in the development of the intestinal tract leads to an improvement of the intestinal surfaces to absorb nutrients and/or dietary additives, this increase being at least partly due to an increase in gut surface area, for example through an increase in villus height.
    Type: Grant
    Filed: October 11, 2000
    Date of Patent: January 17, 2006
    Assignee: Ewos Limited
    Inventors: Charles Burrells, Paul David Williams
  • Patent number: 6984629
    Abstract: Based on research for compounds that can display a corneal epithelial migration promoting effect in ophthalmology, the present invention provides P2Y receptor agonist corneal epithelial migration promoters, such as phosphoric acid compounds having an adenosyl group, uridyl group, xanthosyl group, guanosyl group, or thymidyl group, or their salts, with excellent corneal epithelial migration promoting effects.
    Type: Grant
    Filed: May 30, 2001
    Date of Patent: January 10, 2006
    Assignees: Santen Pharmaceutical Co., Ltd., Inspire Pharmaceuticals, Inc.
    Inventors: Katsuhiko Nakata, Masatsugu Nakamura, Tsutomu Fujihara, Hiromi Fujita
  • Patent number: 6977246
    Abstract: The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment as well as facilitating sputum induction and expectoration.
    Type: Grant
    Filed: November 6, 2001
    Date of Patent: December 20, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: William Pendergast, Benjamin R. Yerxa, Janet L. Rideout, Suhaib M. Siddiqi
  • Patent number: 6949521
    Abstract: Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2?-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.
    Type: Grant
    Filed: May 4, 2001
    Date of Patent: September 27, 2005
    Assignees: The University of Georgia Research Foundation, Inc., Emory University
    Inventors: Chung K. Chu, Lakshmi P. Kotra, Konstantine Manouilov, Jinfa Du, Raymond Schinazi
  • Patent number: 6946450
    Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2?-deoxy-?-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2?-deoxy-?-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.
    Type: Grant
    Filed: May 13, 2003
    Date of Patent: September 20, 2005
    Assignees: Idenix Pharmaceuticals, Inc., Centre National de la Recherche Scientifique, L'Universite Montpellier II
    Inventors: Gilles Gosselin, Jean-Louis Imbach, Martin L. Bryant
  • Patent number: 6924272
    Abstract: The present invention relates to an agent for the prophylaxis or treatment of diabetic neuropathy, which contains cytidine 5?-diphosphocholine (CDP-choline) as an active ingredient. The agent for the prophylaxis or treatment of diabetic neuropathy of the present invention is effective for neuropathy mainly caused by metabolic disturbance of carbohydrate and is also superior in safety. Neuropathy includes peripheral neuropathy and dysautonomia. CDP-choline is effective even by oral administration.
    Type: Grant
    Filed: September 3, 2002
    Date of Patent: August 2, 2005
    Assignee: Yamasa Corporation
    Inventors: Kazuki Endo, Toichi Abiru, Junzo Kamei
  • Patent number: 6921755
    Abstract: A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5?-triphosphate (UTP), dinucleotides, cytidine 5?-triphosphate (CTP), adenosine 5?-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.
    Type: Grant
    Filed: November 9, 2001
    Date of Patent: July 26, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, Karla M. Jacobus, William Pendergast, Janet L. Rideout
  • Patent number: 6919320
    Abstract: The invention relates to compositions comprising 2?-deoxyribonucleosides. The invention also relates to methods of accelerating the healing of wounds, abrasions, cuts, incisions, and superficial burns induced by heat, sunlight, chemical agents, or infections, and methods for ameliorating the effects of aging of the epidermal tissues comprising administering the compositions of the present invention to an animal.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: July 19, 2005
    Assignee: Wellstat Therapeutics Corporation
    Inventors: Reid Warren von Borstel, Michael Kevin Bamat
  • Patent number: 6916794
    Abstract: A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5?-triphosphate (UTP), dinucleotides, cytidine 5?-triphosphate (CTP), adenosine 5?-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.
    Type: Grant
    Filed: January 3, 2002
    Date of Patent: July 12, 2005
    Assignee: Inspire Pharmaceutical, Inc.
    Inventors: Benjamin R. Yerxa, Karla M. Jacobus, William Pendergast, Janet L. Rideout
  • Patent number: 6911460
    Abstract: The present invention relates to methods of treating viral or fungal infections using 3-aminopyridine-2-carboxyaldehyde thiosemicarbazone (3-AP) and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) and its prodrug forms and to pharmaceutical compositions comprising these compounds.
    Type: Grant
    Filed: April 18, 2002
    Date of Patent: June 28, 2005
    Assignees: Vion Pharmaceuticals, Inc., Yale University
    Inventors: Ivan C. King, Terrance W. Doyle, Mario Sznol, Alan C. Sartorelli, Yung-Chi Cheng
  • Patent number: 6897201
    Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a nucleoside 5?-pyrophosphate pyranoside or analogue, which is defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as found in glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with another therapeutic agent or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure. The present invention also provides a novel composition comprising a nucleoside 5?-pyrophosphate pyranoside or analogues.
    Type: Grant
    Filed: February 27, 2002
    Date of Patent: May 24, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Jose L. Boyer, Benjamin R. Yerxa, Robert Plourde, Jr., Edward G. Brown
  • Patent number: 6887858
    Abstract: A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5?-triphosphate [UTP], dinucleotides, cytidine 5?-triphosphate [CTP], adenosine 5?-triphosphate [ATP], or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.
    Type: Grant
    Filed: February 6, 1998
    Date of Patent: May 3, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, Karla M. Jacobus, William Pendergast, Janet L. Rideout
  • Patent number: 6881725
    Abstract: The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and pain associated with diseases. The P2X receptor antagonists particularly useful for this invention are mononucleoside polyphosphate derivatives or dinucleoside polyphosphate derivatives of general Formula I. The compounds of the present method can be used alone to treat pain. The compounds of the present method can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the overall pain-reducing effect in a subject in need of such treatment.
    Type: Grant
    Filed: January 31, 2003
    Date of Patent: April 19, 2005
    Assignee: Inspire Pharmaceuticals Inc.
    Inventors: Benjamin R. Yerxa, Ward M. Peterson, Christopher S. Crean
  • Patent number: 6872710
    Abstract: The present invention is directed to P1, P4-di(uridine 5?)-tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?)-tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?)-tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.
    Type: Grant
    Filed: April 14, 2003
    Date of Patent: March 29, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, Edward G. Brown
  • Patent number: 6867199
    Abstract: The present invention relates to certain novel dinucleoside polyphosphates of general Formulae I, II and III, and formulations thereof which are selective ligands of the P2Y purinergic receptors. Applicants have discovered that dinucleoside polyphosphates of general Formulae I, II and III are effective in clearing retained mucous secretions, balancing tissue hydration and fluid secretion, and/or inhibiting or preventing early stages of platelet activation, platelet degranulation, and platelet aggregation.
    Type: Grant
    Filed: April 28, 2003
    Date of Patent: March 15, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Janet L. Rideout, Benjamin R. Yerxa, Sammy Ray Shaver, James G. Douglass, III
  • Patent number: 6864243
    Abstract: The present invention provides a method of preventing or treating retinal degeneration arising from pathophysiological or physical conditions. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor ligand, in an amount effective to elevate its extracellular concentration to activate retinal glial and neuronal cell surface P2Y receptors and mount a neuroprotective response. Methods of administering including intravitreal bolus and sustained administrations, transscleral delivery, topical, and systemic administrations. The pharmaceutical composition useful in this invention comprises a P2Y purinergic receptor agonist, which include uridine 5?-di-and triphosphate (UDP, UTP) and their analogs, adenosine 5?-diphosphate (ADP) and its analogs, cytidine 5?-di-and triphosphate (CDP, CTP) and their analogs, and dinucleoside polyphosphate compounds.
    Type: Grant
    Filed: May 12, 2000
    Date of Patent: March 8, 2005
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventor: Ward M. Peterson
  • Patent number: 6858591
    Abstract: The invention provides compounds of the Formula 1 wherein the definitions of m, n, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are in the specification. These compounds are useful as antibacterial agents.
    Type: Grant
    Filed: April 25, 2002
    Date of Patent: February 22, 2005
    Assignee: Wyeth Holdings Corporation
    Inventors: Ayako Yamashita, Emily Boucher Norton
  • Patent number: 6852688
    Abstract: The subject invention provides novel methods and materials for treating diabetic retinopathy. One embodiment of the subject invention involves the co-administration of a somatostatin, or analogue thereof, and a thryoid-related substance such as thyroxine. Somatostatin or thyroid-related substance can be administered in combination, or separately through the same or different modes of administration.
    Type: Grant
    Filed: March 12, 2001
    Date of Patent: February 8, 2005
    Assignee: University of Florida
    Inventor: Maria Grant
  • Patent number: 6838447
    Abstract: Disclosed are compositions that include triboelectrically chargeable nucleotide particles of less than 50 ?m diameter and carrier particles. In one example, a substrate is selectively patterned with the compositions, e.g., by transfer from a selectively charged surface. The compositions can be used to synthesize nucleic acid arrays.
    Type: Grant
    Filed: March 26, 2002
    Date of Patent: January 4, 2005
    Assignee: Linden Technologies, Inc.
    Inventor: Tai-Nang Huang
  • Patent number: 6833362
    Abstract: A composition for accelerating the disposal of ethanol from bodily fluid. Certain additives can accelerate the metabolic oxidation of ethanol, and others in addition act as catalysts or “pseudo” enzymes for the oxidation. Additives include the oxidant Nicotinamide Adenine Dinucleotide and a variety of other additives such as transition metal ions and complexes thereof which favor the oxidation reaction. The compositions described can act as a sobriety inducer and/or as an effective palliative for the unpleasant effects of overuse of ethanol.
    Type: Grant
    Filed: June 7, 2001
    Date of Patent: December 21, 2004
    Inventors: Ward Beryl Bowen, Jr., Daniel Salman Daniel
  • Patent number: 6833361
    Abstract: Conformationally restricted 2′, 4′-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2′ and C4′ of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.
    Type: Grant
    Filed: April 30, 2002
    Date of Patent: December 21, 2004
    Assignee: Ribapharm, Inc.
    Inventors: Zhi Hong, Haoyun An
  • Patent number: 6825177
    Abstract: Methods for increasing the elimination half-life of key metabolites such as d4T by administering an aryl phosphate derivative of d4T having an electron withdrawing substituent on the aryl group and an amino acid substituent on the phosphate group are described. A preferred aryl phosphate derivative of d4T is HI-113 (d4T-5′-[p-bromophenyl methoxyalaninyl phosphate]). The administration of HI-113 results in more prolonged systemic exposure to the key metabolites, Ala-d4T-MP and d4T, than administration of an equimolar dose of either metabolite. Each metabolite has a significantly longer elimination half life when formed in vivo from the administration of HI-113 than when the metabolite is administered directly.
    Type: Grant
    Filed: October 19, 2001
    Date of Patent: November 30, 2004
    Assignee: Parker Hughes Institute
    Inventors: Fatih Uckun, Chun-Lin Chen, Taracad K. Venkatachalam, Zhoa-Hai Zhu
  • Patent number: 6818629
    Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.
    Type: Grant
    Filed: March 25, 2003
    Date of Patent: November 16, 2004
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Ward M. Peterson, Benjamin R. Yerxa
  • Patent number: 6800616
    Abstract: Disclosed is a method of treating an HIV-infected host including administering to the host a therapeutic agent that is cytotoxic or cytostatic with respect to CD4+ T cells, but has reduced cytotoxic or cytostatic activity with respect to T lymphocyte stem cells, in a CD4+ T cell cytotoxic or cytostatic effective amount. Also disclosed is a method of treating an HIV-infected host including administering highly active antiretroviral therapy; and coadministering to the host a therapeutic agent that is cytotoxic or cytostatic with respect to CD4+ T cells, but has reduced cytotoxic or cytostatic activity with respect to T lymphocyte stem cells, in a CD4+ T cell cytotoxic or cytostatic effective amount.
    Type: Grant
    Filed: February 26, 1998
    Date of Patent: October 5, 2004
    Assignee: SuperGen, Inc.
    Inventor: Simeon M. Wrenn, Jr.
  • Patent number: 6787525
    Abstract: The invention relates to glyceryl nucleotides of the formula Ia in which a) one of the radicals A1, A2 and A3 is a hydrogen atom or a radical selected from hydroxyl, mercapto, alkyl, alkenyl, polyoxyalkenyl, aryl, acyl, alkyloxy, alkenyloxy, polyoxyalkenyloxy, acyloxy, aryloxy, alkylthio, alkenylthio, acylthio and arylthio, where the alkyl, alkenyl and acyl radicals are optionally substituted by from 1 to 3 aryl radicals; and b1) two of the remaining radicals A1, A2 and A3 are two nucleoside groups which are different from each other; or b2) one of the remaining radicals A1, A2 and A3 is a nucleoside group and the other of the remaining radicals is a hydroxycarbonyl group, where at least one of the nucleoside groups is not a naturally occurring nucleoside group; to processes for preparing these compounds, to pharmaceutical remedies which comprise these compounds, and to the use of these compounds for treating cancer diseases and infectious diseases.
    Type: Grant
    Filed: September 12, 2001
    Date of Patent: September 7, 2004
    Inventors: Herbert Schott, Peter Stephan Ludwig
  • Patent number: 6784161
    Abstract: The present invention relates to a method for the treatment or prevention of Flavivirus infections using nucleoside analogues in a host comprising administering a therapeutically effective amount of a compound having the formula I or a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: February 20, 2001
    Date of Patent: August 31, 2004
    Assignee: BioChem Pharma, Inc.
    Inventors: Hicham Moulay Alaoui Ismaili, Yun-Xing Cheng, Jean-François Lavallée, Arshad Siddiqui, Richard Storer
  • Patent number: 6774121
    Abstract: The invention discloses prodrugs comprising anti-proliferative drugs covalently linked, via bridging group, to a phospholipid moiety such that the active species is preferentially released, preferably by enzymatic cleavage, at the required site of action. The invention further discloses pharmaceutical compositions said prodrugs and the uses thereof for the treatment of diseases and disorders related to inflammatory, to degenerative or atrophic conditions, and to uncontrolled cell growth. FIG. 1 depicts a graph of animal survival during the course of an experiment wherein mice were i.p. transplanted with 11210 mouse leukemia cells and then treated with vehicle only (squares), MTX (triangles) or molar equivalent dose of DP-MTX071 (circles) according to the regiment described example in Example 11.
    Type: Grant
    Filed: March 13, 2002
    Date of Patent: August 10, 2004
    Assignee: D-Pharm, Ltd.
    Inventors: Alexander Kozak, Israel Shapiro, Marina Vinnikova, Leonid Ershov, Alexander Senderikhin, Oran Ayalon
  • Publication number: 20040116359
    Abstract: The invention provides compositions comprising formula 1 steroids, e.g., 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.
    Type: Application
    Filed: December 21, 2002
    Publication date: June 17, 2004
    Inventors: Clarence Nathaniel Ahlem, James Martin Frincke, Luis Daniel dos Anjos de Carvalho, William Heggie, Patrick T. Prendergast, Christopher L. Reading, Krupakar Paul Thadikonda, Russell Neil Vernon
  • Publication number: 20040092476
    Abstract: Compounds of Formula I, their preparation and uses are described: 1
    Type: Application
    Filed: October 31, 2003
    Publication date: May 13, 2004
    Inventors: Serge Boyer, Mark D. Erion
  • Publication number: 20040077585
    Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.
    Type: Application
    Filed: October 8, 2003
    Publication date: April 22, 2004
    Inventors: Ward M. Peterson, Benjamin R. Yerra
  • Publication number: 20040063651
    Abstract: Excellent remedies for hepatitis C which contain as the active ingredients a 3′-deoxy-3′-fluorouridine derivatives and a 1-(3′-deoxy-fluoro-&bgr;-L-ribofuranosyl)uracil derivative and show little side effects.
    Type: Application
    Filed: July 31, 2003
    Publication date: April 1, 2004
    Inventors: Masahiko Morioka, Masaru Ubasawa, Masaaki Arai
  • Patent number: 6713458
    Abstract: The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5′-tetraphosphate), and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5′-tetraphosphate) (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture. Therapeutic uses of Formula I include treatment of sinusitis, otitis media, dry eye, retinal detachment, nasolacrimal duct obstruction, female infertility and irritation due to vaginal dryness, via increased mucus secretions and hydration of the epithelial surface. wherein: X is Na, NH4 or H, provided that all X groups are not H.
    Type: Grant
    Filed: November 24, 1999
    Date of Patent: March 30, 2004
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Benjamin R. Yerxa, William Pendergast
  • Patent number: 6706876
    Abstract: The present invention is directed to a pulp useful for making lyocell fibers. The pulp has a degree of polymerization from about 300 to about 1000; an alpha cellulose content of less than about 90% and in one instance can be made in a roll form. The degree of polymerization can be modified by acid hydrolysis, steam explosion; or alkaline enzymate degradation.
    Type: Grant
    Filed: September 18, 2001
    Date of Patent: March 16, 2004
    Assignee: Weyerhaeuser Company
    Inventors: Mengkui Luo, Vincent A. Roscelli, Amar N. Neogi
  • Patent number: 6703376
    Abstract: A method of promoting drainage of mucous secretions in the congested airways of a bedridden/immobilized patient or an intubated/mechanically-ventilated patient is disclosed. The method comprises administering to the airways of the patient a uridine phosphate such as uridine 5′-triphsophate(UTP) or P1,P4-di(uridine-5′) tetraphosphate, an analog of UTP, or any other analog, in an amount effective to promote drainage of fluid in the congested airways, including sinuses, to create the ciliary beat frequency of cilia on the surface lumina epithelia cells, to increase the secretions of mucous by goblet cells and to promote the clearance of retained secretions by hydrating mucous secretions, by stimulating ciliary beat frequency in the airways and by stimulating surfactant production. Pharmaceutical formulations and methods of making the same are also disclosed.
    Type: Grant
    Filed: December 22, 1998
    Date of Patent: March 9, 2004
    Assignee: Inspire Pharmaceuticals, Inc.
    Inventors: Karla M. Jacobus, H. Jeff Leighton