3287results about How to "Reduce dose" patented technology

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

This invention relates to compounds, compositions, and methods useful for modulating BCL2 gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of BCL2 gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of BCL2 genes (e.g., BCL2, BCL-XL, BCL2-L1, MCL-1 CED-9, BAG-1, E1B-194 and / or BCL-A1). The small nucleic acid molecules are useful in the treatment of cancer, malignant blood disease, polycytemia vera, idiopathic myelofibrosis, essential thrombocythemia, myelodysplastic syndromes, autoimmune disease, viral infection, and proliferative diseases and conditions

This invention is directed to a novel method and composition for the treatment of diabetes mellitus (Type I, Impaired Glucose Tolerance ["IGT"]and Type II). More specifically, this invention pertains to a novel method of treating diabetes mellitus by incorporating a therapeutic amount of one or more insulin sensitizers along with one or more of an orally ingested insulin, an injected insulin, a sulfonylurea, a biguanide or an alpha-glucosidase inhibitor for the treatment of diabetes mellitus.

The present invention relates to biphenyl-pyrazole compounds and in particular biphenyl-pyrazolecarboxamides. The invention further provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by antagonism or inverse agonism of the CB1 receptor, such as obesity, smoking cessation, and normalization of blood lipid composition.

This invention relates to compounds, compositions, and methods useful for modulating wingless (WNT) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of WNT gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of WNT genes such as WNT3A and WNT7A.

This invention relates to compounds, compositions, and methods useful for modulating tumor necrosis factor and / or tumor necrosis factor receptor gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of tumor necrosis factor and / or tumor necrosis factor receptor gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of tumor necrosis factor and / or tumor necrosis factor receptor genes, (TNF and / or TNF receptor).

A test strip with a sample receiving chamber having a novel flared portion that terminates in a sample receiving opening. The flared portion provides a reservoir from which sample fluid can be drawn into the capillary or sample receiving chamber. The wider opening provided by the present invention is easier to “target” with a sample fluid. In preferred embodiments, the hydrophilic reagent layer extends to the dosing end or side of the test strip and further promotes wicking of the sample into the sample receiving chamber and thus reduces dose hesitation. In other preferred embodiments, a tapered dosing end is provided on the test strip in combination with the flared portion, and this combination create a test strip that will draw sample fluid into the sample receiving chamber regardless of where along the dosing edge of the test strip the fluid sample makes contact.

Oligonucleotides for genotyping the thymidylate synthase gene are provided. The number of tandem repeats in the promoter region of the thymidylate synthase gene can be identified based on the hybridization of an oligonucleotide of the invention to the genomic DNA of a subject. Therefore, the genotype of the thymidylate synthase gene can be identified based on the number of tandem repeats. The genotype relates to the responsiveness of a subject towards an antitumor agent.

Sustained release dosage forms for twice daily oral dosing to a human patient for providing relief from pain are provided. The sustained release dosage form comprises an immediate release component and a sustained release component, wherein the immediate release component and the sustained release component collectively contain a therapeutically effective amount of an opioid analgesic and a therapeutically effective amount of nonopioid analgesic. In a preferred embodiment, the nonopioid analgesic is acetaminophen and the opioid analgesic is hydrocodone and pharmaceutically acceptable salts thereof, and in preferred embodiments, the pharmaceutically acceptable salt is bitartrate. The dosage forms produce plasma profiles in a patient characterized by a Cmax for hydrocodone of between about 0.6 ng / mL / mg to about 1.4 ng / mL / mg and an AUC for hydrocodone of between about 9.1 ng*hr / mL / mg to about 19.9 ng*hr / mL / mg (per mg hydrocodone bitartrate administered) and a Cmax for acetaminophen of between about 2.8 ng / mL / mg and 7.9 ng / mL / mg and an AUC for acetaminophen of between about 28.6 ng*hr / mL / mg and about 59.1 ng*hr / mL / mg (per mg acetaminophen administered) after a single dose.

Provided is an improved treatment for Parkinson's Disease where the efficacy of L-Dopa treatment is increased by including gene therapy in the treatment regimen. The combination therapy results in long-term improvements in response to L-Dopa and diminished side effects caused by L-Dopa.

Pharmaceutical compositions comprising 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile and pharmaceutically acceptable salts thereof are provided as well as kits and articles of manufacture comprising the pharmaceutical compositions as well as methods of using the pharmaceutical compositions.

A test strip or biosensor comprising a base substrate on which an electrode system is formed. One or more laminate layers overlie the base substrate to form a sample-receiving chamber in which a reagent is deposited. An opening is provided from the sample-receiving chamber to the exterior of the biosensor. The layers and the base substrate are laser welded to secure the biosensor. One of the layer and base substrate is light transmissive to allow laser welding at the interface therebetween. The biosensor may be formed from a series of continuous webs that are subsequently sliced to form individual biosensors.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

Sustained release dosage forms for twice daily oral dosing to a human patient for providing relief from pain are provided. The sustained release dosage form comprises an immediate release component and a sustained release component, wherein the immediate release component and the sustained release component collectively contain a therapeutically effective amount of an opioid analgesic and a therapeutically effective amount of nonopioid analgesic. In a preferred embodiment, the nonopioid analgesic is acetaminophen and the opioid analgesic is hydrocodone and pharmaceutically acceptable salts thereof, and in preferred embodiments, the pharmaceutically acceptable salt is bitartrate. The dosage forms produce plasma profiles in a patient characterized by a Cmax for hydrocodone of between about 0.6 ng / mL / mg to about 1.4 ng / mL / mg and an AUC for hydrocodone of between about 9.1 ng*hr / mL / mg to about 19.9 ng*hr / mL / mg (per mg hydrocodone bitartrate administered) and a Cmax for acetaminophen of between about 2.8 ng / mL / mg and 7.9 ng / mL / mg and an AUC for acetaminophen of between about 28.6 ng*hr / mL / mg and about 59.1 ng*hr / mL / mg (per mg acetaminophen administered) after a single dose.

Oligonucleotide analogues comprising modified intersubunit linkages and / or modified 3′ and / or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

The invention involves administration of an imidazoquinoline agent in combination with another therapeutic agent. The combination of drugs may be administered in synergistic amounts or in various dosages or at various time schedules. The invention also relates to kits and compositions concerning the combination of drugs. The combinations can be used to enhance ADCC, stimulate immune responses and / or patient and treat certain disorders.

The present invention provides a controlled release oral pharmaceutical composition having a therapeutically effective amount of one or more pharmacologically active agent having low bioavailability; one or more solubilizers; one or more biocompatible swelling agents; and a swelling enhancer. The swelling agent, in combination with swelling enhancer, swells in the presence of water in gastric fluid such that the size of the dosage form is sufficiently increased to provide retention of the dosage form in the stomach of a patient, which gradually erodes within the gastrointestinal tract over a prolonged time period.

The present invention is an indirect AMFPI wherein a phosphor such as a structured cesium iodide (CsI) is used to convert x-ray energy to optical photons or a charge, which is then detected by a two-dimensional array of either thin-film transistors (TFTs) such as an amorphous a-Se TFTs or a photodiode array. A scanning control circuit generates pulses to turn on the TFTs one row at a time, and thus the charge in the individual arrays is transferred from the TFT to one or more external charge-sensitive amplifiers. The charge-sensitive amplifiers are shared by all the pixels in the same column. The two-dimensional array can be read in real time.

Oligonucleotide analogues conjugated to carrier peptides are provided. The disclosed compounds are useful for the treatment of various diseases, for example diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

The invention relates to a medicine of a bispecific monoclonal antibody, and especially to a medicine of a bispecific monoclonal antibody to human vascular endothelial growth factor (VEGF / VEGF-A) and platelet-derived growth factor receptor (PDGFR) for resistance to angiogenesis of tumor. The bispecific antibody to VEGF / PDGFR beta provided in the invention is characterized in that: a monoclonal antibody to VEGF is used as the base for the antibody and a single chain antibody to PDGFR beta is connected with the terminal of FC segment of the monoclonal antibody to VEGF to form the bispecific antibody to VEGF / PDGFR beta. The bispecific antibody related to in the invention is obtained by employing technical means like gene engineering and constructing antibody segments which identify VEGF and PDGFR beta in a same antibody molecule that can be specifically bound with the two antibody segments; the effect of the bispecific antibody on inhibiting angiogenesis of tumor issue is obviously superior to that of a single antibody to VEGF; and the bispecific antibody has good activity in resisting tumors.

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac / DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language