Abstract: Lipid-containing prodrugs are provided for treating viral infections due to herpes, influenza, hepatitis B, Epstein-Barr, and varicella zoster viruses, as well as cytomegalovirus and derivatives of antiviral agents. The compounds comprise phosphonoacids having antiviral activity which are linked, either through the phosphate group or carboxyl group of the phosphonoacid, to one of a selected group of lipids. Phosphonoacetic acid and phosphonoformic acid are thus linked to phospholipids, glycerolipids, sphingolipids, glycolipids, or fatty acids. The compounds persist, after intracellular hydrolysis, as the antiviral phosphonoacids. The lipid prodrugs are effective in improving the efficacy of antiviral phosphonoacids by prolonging their antiviral activity following administration.
Abstract: Methods are described for the identification and preparation of nucleic acid ligands to human neutrophil elastase. Included in the invention are specific RNA and DNA ligands to elastase identified by the SELEX method.
Abstract: Methods are described for the identification and preparation of high-affinity nucleic acid ligands to TGF.beta.. Included in the invention are specific RNA and ssDNA ligands to TGF.beta.1 identified by the SELEX method. Also included are RNA ligands that inhibit the interaction of TGF.beta.1 with its receptor.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
March 24, 1998
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Penelope J. Toothman, Steven Ringquist, Larry Gold
Abstract: Methods are described for the identification and preparation of high-affinity nucleic acid ligands to TGF.beta.. Included in the invention are specific RNA and ssDNA ligands to TGF.beta.1 identified by the SELEX method. Also included are RNA ligands that inhibit the interaction of TGF.beta.1 with its receptor.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
March 24, 1998
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Penelope J. Toothman, Steven Ringquist, Larry Gold
Abstract: Methods are described for the identification and preparation of high-affinity nucleic acid ligands to HIV-1 GAG, Included in the invention are specific RNA ligands to HIV-1 GAG identified by the SELEX method, Also included are RNA ligands that inhibit the function of HIV-1 GAG.
Abstract: Methods are described for the identification and preparation of high-affinity nucleic acid ligands to PDGF. Included in the invention are specific ssDNA and RNA ligands to PDGF identified by the SELEX method.
Abstract: This invention discloses a method for coevolving products from two or more reactants, along with the nucleic acid that can facilitate the reaction for making the products. The invention further discloses the products and facilitating nucleic acids produced by said method.
Abstract: This invention discloses a method for coevolving products from two or more reactants, along with the nucleic acid that can facilitate the reaction for making the products. The invention further discloses the products and facilitating nucleic acids produced by said method.
Abstract: A liposome formulation containing a Vinca Alkaloid and an ion in an aqueous phase of the liposome. The liposomes also comprise distearoylphosphatidyl choline, cholestrol and disteraroylphosphatidylglycerol. A method for enhancing the efficacy and tumor targeting properties of liposomal vinca alkaloid formulations containing unilamellar vesicles.
Abstract: This invention discloses high-affinity oligonucleotide ligands to complex tissue targets, specifically nucleic acid ligands having the ability to bind to complex tissue targets, and the methods for obtaining such ligands. Tissue targets comprise cells, subcellular components, aggregates or cells, collections of cells, and higher ordered structures. Specifically, nucleic acid ligands to red blood cells ghosts, glioblastomas, and lymphomas are described.
Type:
Grant
Filed:
May 3, 1995
Date of Patent:
January 27, 1998
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Kirk B. Jensen, Hang Chen, Kevin N. Morris, Andrew Stephens, Larry Gold
Abstract: A method of selecting nucleic acids on the basis of physical structure is disclosed. A modification of the Systematic Evolution of Ligands by Exponential enrichment (SELEX) is used in conjunction with methods for differentiating between nucleic acid molecules on the basis of physical structure, such as chromatography, gel electrophoresis, solubility, and solvent partitioning. The disclosed method may be used in selecting single stranded DNA or RNA, or double stranded DNA or RNA. An example of the method selected nucleic acids of bent DNA. This method represents a new and powerful approach to select nucleic acid molecules with the physical structure required for specific biological activity, for example, in the regulation of gene expression.
Abstract: This application provides methods for identifying nucleic acid ligands capable of covalently interacting with targets of interest. The nucleic acids can be associated with various functional units. The method also allows for the identification of nucleic acids that have facilitating activities as measured by their ability to facilitate formation of a covalent bond between the nucleic acid, including its associated functional unit, and its target.
Type:
Grant
Filed:
March 8, 1995
Date of Patent:
January 6, 1998
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Larry Gold, Bruce Eaton, Drew Smith, Matthew Wecker, Kirk Jensen
Abstract: A new class of nucleic acid compounds, referred to as nucleic acid ligands, have been shown to exist that have a specific binding affinity for three dimensional molecular targets. In a preferred embodiment the ligands are identified by the method of the invention referred to as the Systematic Evolution of Ligands by EXponential enrichment (SELEX), wherein a candidate mixture of nucleic acids are iteratively enriched in high affinity nucleic acids and amplified for further partitioning.
Abstract: This invention discloses high-affinity oligonucleotide ligands to the thermostable Taq polymerase and Tth polymerase. Specifically, this invention discloses DNA ligands having the ability to bind to the Taq and Tth polymerases and the methods for obtaining such ligands. The ligands are capable of inhibiting polymerases at ambient temperatures.
Abstract: An improved liposomal cyclosporin therapeutic formulation, comprising phosphatidylcholine, cholesterol, dimyristoylphosphatidylglycerol and a cyclosporin in a mole ratio of about 28:1:3:1 to 40:1:3:1 which are stable in mammalian blood.
Abstract: This invention discloses high-affinity oligonucleotide ligands to complex tissue targets, specifically nucleic acid ligands having the ability to bind to complex tissue targets, and the methods for obtaining such ligands. Tissue targets comprise cells, subcellular components, aggregates or cells, collections of cells, and higher ordered structures. Specifically, nucleic acid ligands to peripheral blood mononuclear cells (PBMC), fibrin clots, and carotid arteries are described.
Abstract: A process for preparing a liposomal cyclosporin therapeutic formulation, which comprises dissolving a combination of a neutral and negatively charged phospholipid and a cyclosporin in an organic solvent; drying the solution to form a solid phase, and hydrating the solid phase in an aqueous solution having a pH ranging from 7.5 to 9.5.
Abstract: This invention discloses high-affinity oligonucleotide ligands to human Immunoglobulin E (IgE), specifically RNA and ssDNA ligands having the ability to bind to IgE, and the methods for obtaining such ligands. The ligands are capable of inhibiting the interaction of IgE with its receptor.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
November 11, 1997
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Torsten Walter Wiegand, Diane Tasset, Larry Gold
Abstract: A method is described for generating blended nucleic acid ligands containing non-nucleic acid functional units. Specifically, a SELEX identified RNA ligand to the integrin gpIIbIIIa is conjugated to the peptide Gly-Arg-Gly-Asp-Thr-Pro (SEQ ID NO:1). This blended RNA ligand inhibits the biological activity of gpIIbIIIa with high specificity. Also described is a single-stranded DNA ligand to elastase coupled to N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl (SEQ ID NO:2) ketone. This elastase blended nucleic acid ligand inhibits the biological activity of elastase.
Type:
Grant
Filed:
April 28, 1994
Date of Patent:
November 4, 1997
Assignee:
NeXstar Pharmaceuticals, Inc.
Inventors:
Greg Biesecker, Sumedha D. Jayasena, Larry Gold, Drew Smith, Gary P. Kirschenheuter