WO2007047692B1 - Devices, systems and methods for improving memory and/or cognitive function through brain delivery of sirna - Google Patents

Devices, systems and methods for improving memory and/or cognitive function through brain delivery of sirna

Info

Publication number
WO2007047692B1
WO2007047692B1 PCT/US2006/040591 US2006040591W WO2007047692B1 WO 2007047692 B1 WO2007047692 B1 WO 2007047692B1 US 2006040591 W US2006040591 W US 2006040591W WO 2007047692 B1 WO2007047692 B1 WO 2007047692B1
Authority
WO
WIPO (PCT)
Prior art keywords
interfering rna
small interfering
subject
brain
delivery
Prior art date
Application number
PCT/US2006/040591
Other languages
French (fr)
Other versions
WO2007047692A2 (en
WO2007047692A3 (en
Inventor
William F Kaemmerer
Original Assignee
Medtronic Inc
William F Kaemmerer
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medtronic Inc, William F Kaemmerer filed Critical Medtronic Inc
Priority to EP06836357A priority Critical patent/EP1948197A4/en
Publication of WO2007047692A2 publication Critical patent/WO2007047692A2/en
Publication of WO2007047692A3 publication Critical patent/WO2007047692A3/en
Publication of WO2007047692B1 publication Critical patent/WO2007047692B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/111—Antisense spanning the whole gene, or a large part of it
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Abstract

The present invention relates to devices, systems, and methods for improving memory and/or cognitive function by brain delivery of compositions of small interfering RNA or vectors containing the DNA encoding for small interfering RNA. Such compositions can be administered using devices, systems and methods for direct delivery of the compositions to the brain, or using devices, systems, methods of delivery, and compositions that deliver small interfering RNA or vectors containing the DNA encoding the small interfering RNA across the blood-brain barrier. The present invention also provides valuable small interfering RNA vectors, and methods for reduction of BACE1 levels in the hippocampus, cerebral cortex, or other regions of the brain that have beneficial effects on improving memory and/or cognitive function in a subject.

Claims

AMENDED CLAIMS received by the International Bureau on 30 July 2007 (30.05.2007)CLAIMS
1. A method for improving memory or cognitive function in a subject in need thereof, comprising administering to the subject a therapeutically effective dose of a composition that decreases the expression of a beta amyloid cleaving enzyme type 1, or BACEl, in a cell of the nervous system of the subject, wherein the composition comprises a small interfering RNA molecule specific for a BACEl gene and wherein the small interfering RNA molecule specifically suppresses BACEl gene expression in a cell of the nervous system of the subject, wherein said subject is not suffering from dementia of the Alzheimer's type.
2. The method of claim 1 wherein the composition is delivered to the subject by intracranial delivery.
3. The method of claim 1 wherein the composition is delivered to the subject across the blood brain barrier.
4. The method of claim 1 wherein the small interfering RNA is substantially encoded by any one of SEQ ID NOS: 24-40.
5. A method for improving memory or cognitive function in a subject in need thereof, comprising modulating the expression or production of a beta amyloid cleaving enzyme type 1, or BACEl, protein in neurons by intracranial delivery of a small interfering RNA specific for a BACEl gene that reduces said expression or production of said BACEl protein, in a pharmaceutically acceptable carrier, wherein said subject is not suffering from dementia of the Alzheimer's type.
6. A method of delivering a small interfering RNA to a location in the brain of a subject suffering from memory or cognitive impairment comprising the steps of: a. surgically implanting an intracranial access delivery device; and b. infusing a small interfering RNA and/or a vector encoding said small interfering RNA at a predetermined site in the brain, wherein at least one attribute of memory function is improved, wherein said subject is not suffering from dementia of the Alzheimer's type.
7. The method of claim 6, wherein the intracranial access delivery device is an intracranial access port coupled to the proximal end of an intracranial catheter.
8. The method of claim 6, further comprising the step of: implanting a pump outside the brain, the pump coupled to the proximal end of an intracranial catheter.
9. The method of claim 8 comprising operating the pump to deliver a predetermined dosage of the said small interfering RNA or vector encoding said small interfering RNA from the pump through the discharge portion of the said intracranial catheter.
10. The method of claim 8 further comprising the step of periodically refreshing the pump with at least one substance.
11. The method of claim 8 wherein the pump is an infusion pump.
12. The method of claim 8 wherein the infusion pump is an electromechanical pump.
13. The method of claim 8 wherein the infusion pump is an osmotic pump.
14. The method of claim 6 wherein the predetermined site in the brain is the nucleus basalis of Meynert or the cerebral cortex or the hippocampus.
15. The method of claims 6, wherein the small interfering RNA is delivered by a delivery vector.
16. The method of claim 15, wherein the delivery vector is selected from the group consisting of adeno-associated virus, adenovirus, herpes simplex virus, lentivirus and a DNA plasmid.
17. A method of delivering a small interfering RNA across a blood-brain barrier for expression in the brain of a subject suffering from memory or cognitive impairment comprising administering to a subject a composition comprising a receptor-specific nanocontainer, wherein the receptor-specific nanocontainer comprises: a nanocontainer having an exterior surface and an internal compartment; an artificial adeno-associated virus (AAV) vector located within the internal compartment of the nanocontainer, wherein the artificial AAV vector comprises DNA encoding a biologically active agent; one or more blood-brain barrier and brain cell membrane targeting agents; and
108 one or more conjugation agents wherein each targeting agent is connected to the exterior surface of the nanocontainer via at least one of the conjugation agents, wherein said subject is not suffering from dementia of the Alzheimer's type.
18. The method of claim 17, wherein the nanocontainer is a liposome.
19. The method of claim 17, wherein the nanocontainer is a nanoparticle comprised of one or more chemical polymers.
20. The method of claim 17, wherein the artificial AAV vector is for delivery of a single stranded DNA encoding a biologically active agent, the artificial AAV vector comprising the single stranded DNA having AAV-ITRs at the 5 -prime and 3 -prime ends.
21. The method of claim 17, wherein the artificial AAV vector is for delivery of a single stranded DNA encoding the biologically active agent, the artificial AAV vector comprising, in 5-prime to 3-prime order: a 5-prime AAV-ITR; the single stranded DNA; an internal AAV-ITR; a reverse complement of the single stranded DNA; and a 3-prime AAV-ITR.
22. The method of claim 17, wherein the artificial AAV vector is for delivery of a linear, double stranded DNA encoding a biologically active agent, the artificial AAV vector comprising the linear, double stranded DNA having AAV-ITRs at the 5-prime and 3- prime ends of each strand.
23. The method of claim 17 wherein the single stranded DNA encodes a small interfering RNA which is substantially encoded by any one of SEQ ID NOS: 24-40.
24. The method of claim 17, wherein the composition is administered intravenously or intra-arterially.
25. The method of claim 17, wherein the exterior surface of the nanocontainer defines a sphere having a diameter of at most 200 nanometers.
109
26. The method of claim 17, wherein at least 5 and at most 1000 blood-brain barrier or brain cell membrane targeting agents are conjugated to the exterior surface of the nanocontainer.
27. The method of claim 17, wherein at least 25 and at most 40 blood-brain barrier or brain cell membrane targeting agents are conjugated to the exterior surface of the nanocontainer.
28. The method of claim 17, wherein the conjugation agent is selected from the group consisting of polyethylene glycol, sphingomyelin, biotin, streptavidin, organic polymers, and combinations thereof.
29. The method of claim 17, wherein the molecular weight of the conjugation agent is at least 1000 Daltons and at most 50,000 Daltons.
30. The method of claim 17, wherein the artificial AAV vector has been thermally treated in at least one heating and cooling cycle.
31. A method for improving memory or cognitive function in a subject, comprising modulating the expression or production of a beta amyloid cleaving enzyme type 1 , or BACEl, protein in neurons by intracranial delivery of a small interfering RNA encoded by any one of SEQ ID NOS: 24-40, that reduces said expression or production of said BACEl protein, in a pharmaceutically acceptable carrier.
32. A method of delivering a small interfering RNA to a location in the brain of a subject suffering from memory or cognitive impairment comprising the steps of: a) surgically implanting an intracranial access delivery device; and b) infusing a small interfering RNA and/or a vector encoding said small interfering RNA containing one or more sequences coded from SEQ ID NOS: 24-40 at a predetermined site in the brain, wherein at least one attribute of said memory or cognitive impairment is improved.
33. A medical system for improving memory or cognitive function in a subject comprising: a) an intracranial access device; b) a mapping means for locating a predetermined location in the brain;
110 c) a deliverable amount of a small interfering RNA or vector encoding said small interfering RNA selected from one or more sequences coded from SEQ ID NOS: 24-40; and d) a delivery means for delivering said small interfering RNA or vector encoding said small interfering RNA to said location of the brain from said intracranial access device.
34. The medical system of claim 33, wherein said intracranial access device is selected from the group consisting of an intracranial catheter, an intracranial access port, an infusion pump an electromechanical pump, and an osmotic pump.
35. The medical system of claim 33, wherein the predetermined location is the nucleus basalis of Meynert or the cerebral cortex or the hippocampus.
36. The medical system of claim 33, wherein the delivery means is injection from an external syringe into an intracranial access port.
111
PCT/US2006/040591 2005-10-19 2006-10-13 Devices, systems and methods for improving memory and/or cognitive function through brain delivery of sirna WO2007047692A2 (en)

Priority Applications (1)

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EP06836357A EP1948197A4 (en) 2005-10-19 2006-10-13 Devices, systems and methods for improving memory and/or cognitive function through brain delivery of sirna

Applications Claiming Priority (2)

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US11/253,393 2005-10-19
US11/253,393 US7618948B2 (en) 2002-11-26 2005-10-19 Devices, systems and methods for improving and/or cognitive function through brain delivery of siRNA

Publications (3)

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WO2007047692A2 WO2007047692A2 (en) 2007-04-26
WO2007047692A3 WO2007047692A3 (en) 2007-08-02
WO2007047692B1 true WO2007047692B1 (en) 2007-10-18

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EP (1) EP1948197A4 (en)
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Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10224750A1 (en) 2002-06-04 2003-12-24 Fresenius Medical Care De Gmbh Device for the treatment of a medical fluid
US7618948B2 (en) 2002-11-26 2009-11-17 Medtronic, Inc. Devices, systems and methods for improving and/or cognitive function through brain delivery of siRNA
US7994149B2 (en) * 2003-02-03 2011-08-09 Medtronic, Inc. Method for treatment of Huntington's disease through intracranial delivery of sirna
ES2485848T3 (en) * 2003-09-12 2014-08-14 University Of Massachusetts RNA interference for the treatment of disorders related to function gain
US8680063B2 (en) 2003-09-12 2014-03-25 University Of Massachusetts RNA interference for the treatment of gain-of-function disorders
CA2568150A1 (en) * 2004-06-21 2006-01-05 Medtronic, Inc. Medical systems and methods for delivering compositions to cells
US7935074B2 (en) 2005-02-28 2011-05-03 Fresenius Medical Care Holdings, Inc. Cassette system for peritoneal dialysis machine
US8197231B2 (en) 2005-07-13 2012-06-12 Purity Solutions Llc Diaphragm pump and related methods
WO2007022470A2 (en) * 2005-08-18 2007-02-22 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating neurological disease
US9273356B2 (en) 2006-05-24 2016-03-01 Medtronic, Inc. Methods and kits for linking polymorphic sequences to expanded repeat mutations
US9375440B2 (en) 2006-11-03 2016-06-28 Medtronic, Inc. Compositions and methods for making therapies delivered by viral vectors reversible for safety and allele-specificity
US8324367B2 (en) 2006-11-03 2012-12-04 Medtronic, Inc. Compositions and methods for making therapies delivered by viral vectors reversible for safety and allele-specificity
WO2008143774A2 (en) * 2007-05-01 2008-11-27 University Of Massachusetts Methods and compositions for locating snp heterozygosity for allele specific diagnosis and therapy
KR20100017422A (en) * 2007-05-15 2010-02-16 헬리콘 테라퓨틱스 인코퍼레이티드 Methods of identifying genes involved in memory formation using small interfering rna(sirna)
US8183221B2 (en) * 2007-09-05 2012-05-22 Medtronic, Inc. Suppression of SCN9A gene expression and/or function for the treatment of pain
PT103865A (en) * 2007-10-25 2009-05-15 Univ De Coimbra NANO-LIPID BASIC CONVEYORS FOR DIRECT DELIVERY OF VIRAL VECTORS AND PROCESS FOR THEIR PRODUCTION
US8192401B2 (en) 2009-03-20 2012-06-05 Fresenius Medical Care Holdings, Inc. Medical fluid pump systems and related components and methods
EP2427766B1 (en) * 2009-05-08 2015-07-29 Eli Lilly and Company Human fg01 gene and its applications
US20100286252A1 (en) * 2009-05-08 2010-11-11 Functional Genetics, Inc. Human fg01 gene and its applications
CA2767668C (en) 2009-07-15 2017-03-07 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
US20110033463A1 (en) * 2009-08-06 2011-02-10 Medtronic, Inc. Apheresis, administration of agent, or combination thereof
US8720913B2 (en) 2009-08-11 2014-05-13 Fresenius Medical Care Holdings, Inc. Portable peritoneal dialysis carts and related systems
US20110052666A1 (en) * 2009-09-03 2011-03-03 Medtronic, Inc. Compositions, Methods, and Systems for SIRNA Delivery
WO2011087804A2 (en) 2009-12-21 2011-07-21 Medtronic, Inc. Peptide-polynucleotide compositions, and methods for transfecting a cell with dna and treatment of neurodegenerative disease
DE102010053973A1 (en) 2010-12-09 2012-06-14 Fresenius Medical Care Deutschland Gmbh Medical device with a heater
EP2654825B1 (en) 2010-12-20 2017-08-02 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
US9624915B2 (en) 2011-03-09 2017-04-18 Fresenius Medical Care Holdings, Inc. Medical fluid delivery sets and related systems and methods
EP3006059B1 (en) 2011-04-21 2017-09-27 Fresenius Medical Care Holdings, Inc. Medical fluid pumping systems and related devices and methods
US9186449B2 (en) 2011-11-01 2015-11-17 Fresenius Medical Care Holdings, Inc. Dialysis machine support assemblies and related systems and methods
US9610392B2 (en) 2012-06-08 2017-04-04 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
US9500188B2 (en) 2012-06-11 2016-11-22 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
US9265458B2 (en) 2012-12-04 2016-02-23 Sync-Think, Inc. Application of smooth pursuit cognitive testing paradigms to clinical drug development
CA2893427C (en) 2012-12-24 2023-01-10 Neurogastrx, Inc. Methods for treating gi tract disorders
US9380976B2 (en) 2013-03-11 2016-07-05 Sync-Think, Inc. Optical neuroinformatics
US9561323B2 (en) 2013-03-14 2017-02-07 Fresenius Medical Care Holdings, Inc. Medical fluid cassette leak detection methods and devices
US10117985B2 (en) 2013-08-21 2018-11-06 Fresenius Medical Care Holdings, Inc. Determining a volume of medical fluid pumped into or out of a medical fluid cassette
EP3119406B1 (en) * 2014-03-18 2021-01-20 Carmel-Haifa University Economic Corporation Ltd Methods for improving cognitive function via modulation of quinone reductase 2
CA2966624A1 (en) * 2014-11-06 2016-05-12 Ibis Biosciences, Inc. Malat-1, a non-coding rna, is a target for the regulation of learning and memory
CN114717264A (en) 2014-11-14 2022-07-08 沃雅戈治疗公司 Compositions and methods for treating Amyotrophic Lateral Sclerosis (ALS)
US11207461B2 (en) 2015-07-30 2021-12-28 Anoop U. R Drug delivery system and method for controlled and continuous delivery of drugs into the brain by bypassing the blood brain barrier
EP3429567B1 (en) 2016-03-16 2024-01-10 The J. David Gladstone Institutes Methods and compositions for treating obesity and/or diabetes and for identifying candidate treatment agents
WO2018204786A1 (en) 2017-05-05 2018-11-08 Voyager Therapeutics, Inc. Compositions and methods of treating amyotrophic lateral sclerosis (als)
WO2018204803A1 (en) * 2017-05-05 2018-11-08 Voyager Therapeutics, Inc. Compositions and methods of treating huntington's disease
WO2019023217A1 (en) * 2017-07-25 2019-01-31 Dignity Health Methods of treating neurodegenerative diseases

Family Cites Families (162)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3588114T2 (en) * 1984-04-19 1997-02-06 Hitachi Ltd Superconducting arrangement
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
GB2181691B (en) 1985-10-21 1990-05-23 Porvair Ltd Gloves
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US4863195A (en) * 1987-10-02 1989-09-05 Capozzola Carl A Identification tag
US5702716A (en) 1988-10-03 1997-12-30 Atrix Laboratories, Inc. Polymeric compositions useful as controlled release implants
US5800390A (en) 1991-05-24 1998-09-01 Sumitomo Pharmaceuticals Company, Limited Equipment for intracerebral administration of preparations
US5236908A (en) * 1991-06-07 1993-08-17 Gensia Pharmaceuticals, Inc. Methods of treating injury to the central nervous system
FR2685346B1 (en) 1991-12-18 1994-02-11 Cis Bio International PROCESS FOR THE PREPARATION OF DOUBLE-STRANDED RNA, AND ITS APPLICATIONS.
WO1993023569A1 (en) 1992-05-11 1993-11-25 Ribozyme Pharmaceuticals, Inc. Method and reagent for inhibiting viral replication
US5911969A (en) 1992-06-09 1999-06-15 Neorx Corporation Pretargeting protocols for enhanced localization of active agents to target sites
EP1251170A3 (en) 1992-07-17 2002-10-30 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of NF-kappaB dependent animal diseases
US5354326A (en) 1993-01-27 1994-10-11 Medtronic, Inc. Screening cable connector for interface to implanted lead
ES2178654T3 (en) * 1993-08-12 2003-01-01 Neurotech Sa IMMONO-ISOLATED BIOCOMPATIBLE CAPSULES CONTAINING GENETICALLY ALTERED CELLS FOR THE SUPPLY OF BIOLOGICALLY ACTIVE MOLECULES.
AU7676894A (en) 1993-08-27 1995-03-21 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Convection-enhanced drug delivery
US5624803A (en) 1993-10-14 1997-04-29 The Regents Of The University Of California In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom
WO1995016774A1 (en) 1993-12-17 1995-06-22 Spinal Cord Society Method for inducing dna synthesis in neurons
DE69535703T2 (en) * 1994-04-13 2009-02-19 The Rockefeller University AAV-mediated delivery of DNA to cells of the nervous system
US6294202B1 (en) 1994-10-06 2001-09-25 Genzyme Corporation Compositions containing polyanionic polysaccharides and hydrophobic bioabsorbable polymers
US6093160A (en) * 1994-11-21 2000-07-25 Augustine Medical, Inc. Flexible non-contact wound treatment device
WO1996018736A2 (en) 1994-12-13 1996-06-20 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of arthritic conditions, induction of graft tolerance and reversal of immune responses
US5534350A (en) 1994-12-28 1996-07-09 Liou; Derlin Powerfree glove and its making method
AU5545596A (en) 1995-04-28 1996-11-18 Medtronic, Inc. Intraparenchymal infusion catheter system
US7069634B1 (en) 1995-04-28 2006-07-04 Medtronic, Inc. Method for manufacturing a catheter
US5840059A (en) 1995-06-07 1998-11-24 Cardiogenesis Corporation Therapeutic and diagnostic agent delivery
US5942455A (en) 1995-11-14 1999-08-24 Drexel University Synthesis of 312 phases and composites thereof
JPH09268067A (en) 1996-03-29 1997-10-14 Asahi Glass Co Ltd Production of silicon carbide member
US6159948A (en) 1996-04-26 2000-12-12 University Of Ottawa Therapeutic and drug screening methods for the treatment and prevention of neuronal disease
US7189222B2 (en) 1996-04-30 2007-03-13 Medtronic, Inc. Therapeutic method of treatment of alzheimer's disease
US5976109A (en) 1996-04-30 1999-11-02 Medtronic, Inc. Apparatus for drug infusion implanted within a living body
US5735814A (en) 1996-04-30 1998-04-07 Medtronic, Inc. Techniques of treating neurodegenerative disorders by brain infusion
WO2000062828A1 (en) 1996-04-30 2000-10-26 Medtronic, Inc. Autologous fibrin sealant and method for making the same
US6281009B1 (en) 1996-09-11 2001-08-28 The General Hospital Corporation Use of a non-mammalian DNA virus to express an exogenous gene in a mammalian cell
US5882561A (en) 1996-11-22 1999-03-16 Drexel University Process for making a dense ceramic workpiece
GB9701684D0 (en) 1997-01-28 1997-03-19 Smithkline Beecham Plc Novel compounds
US5968059A (en) 1997-03-06 1999-10-19 Scimed Life Systems, Inc. Transmyocardial revascularization catheter and method
GB9706463D0 (en) 1997-03-27 1997-05-14 Medical Res Council A model of inflamation in the central nervous system for use in the study of disease
WO1998046273A2 (en) 1997-04-17 1998-10-22 Paola Leone Delivery system for gene therapy to the brain
AU7135498A (en) 1997-04-17 1998-11-11 Antivirals Inc. Method of treating restenosis by antisense targeting of cmv
US5931861A (en) 1997-04-25 1999-08-03 Medtronic, Inc. Medical lead adaptor having rotatable locking clip mechanism
US5782892A (en) 1997-04-25 1998-07-21 Medtronic, Inc. Medical lead adaptor for external medical device
US6042579A (en) 1997-04-30 2000-03-28 Medtronic, Inc. Techniques for treating neurodegenerative disorders by infusion of nerve growth factors into the brain
US6110459A (en) 1997-05-28 2000-08-29 Mickle; Donald A. G. Transplants for myocardial scars and methods and cellular preparations
US20050282198A1 (en) 1997-05-29 2005-12-22 Interleukin Genetics, Inc. Diagnostics and therapeutics for diseases associated with an IL-1 inflammatory haplotype
ES2218685T3 (en) * 1997-06-13 2004-11-16 Nanodel Technologies Gmbh SYSTEM FOR PHARMACO ADDRESS, PROCEDURE FOR PREPARATION AND USE.
US6231969B1 (en) 1997-08-11 2001-05-15 Drexel University Corrosion, oxidation and/or wear-resistant coatings
US6187906B1 (en) 1997-08-11 2001-02-13 Aukland Uniservices Limited Methods to improve neural outcome
AU9692198A (en) 1997-10-10 1999-05-03 Kevin J. Donahue Gene delivery compositions and methods
US6151525A (en) 1997-11-07 2000-11-21 Medtronic, Inc. Method and system for myocardial identifier repair
AU2970299A (en) 1998-02-10 1999-08-23 Ohio State University Research Foundation, The Compositions and methods for polynucleotide delivery
DE19938960A1 (en) 1998-03-10 2001-02-22 Bisping Hans Juergen Test cable connecting probe to test apparatus, e.g. for testing implanted pacemaker, electrotherapy or electro-diagnostics includes crocodile clip and flexible conductor with spring contact
WO1999050300A1 (en) 1998-03-30 1999-10-07 The Trustees Of The University Of Pennsylvania Method of identifying, diagnosing and treating synuclein positive neurodegenerative disorders
US6436392B1 (en) 1998-05-20 2002-08-20 University Of Iowa Research Foundation Adeno-associated virus vectors
CA2329259C (en) 1998-05-27 2003-08-05 Avigen, Inc. Convection-enhanced delivery of aav vectors
JP2002520748A (en) 1998-07-16 2002-07-09 ザ リサーチ ファウンデーション オブ ステイト ユニヴァーシティ オブ ニューヨーク Apparatus and method for real-time volume processing and universal 3D rendering
US6313268B1 (en) 1998-10-16 2001-11-06 Vivian Y. H. Hook Secretases related to Alzheimer's dementia
US6245884B1 (en) 1998-10-16 2001-06-12 Vivian Y. H. Hook Secretases related to alzheimer's dementia
US6585767B1 (en) 1998-11-23 2003-07-01 Agion Technologies, Inc. Antimicrobial suturing ring for heart valve
US6319905B1 (en) 1998-12-29 2001-11-20 Cell Genesys, Inc. Method of controlling L-Dopa production and of treating dopamine deficiency
DE19910340A1 (en) 1999-03-09 2000-09-21 Juergen C Froelich Improved autologous venous graft
US6835194B2 (en) 1999-03-18 2004-12-28 Durect Corporation Implantable devices and methods for treatment of pain by delivery of fentanyl and fentanyl congeners
US6331427B1 (en) 1999-03-26 2001-12-18 Millennium Pharmaceuticals, Inc. Protease homologs
US6582715B1 (en) 1999-04-27 2003-06-24 Agion Technologies, Inc. Antimicrobial orthopedic implants
JP2002542781A (en) 1999-04-28 2002-12-17 ザ、ボード、オブ、トラスティーズ、オブ、ザ、リーランド、スタンフォード、ジュニア、ユニバーシティ P factor-derived vectors and methods of use
US6310058B1 (en) 1999-05-27 2001-10-30 University Of Notre Dame Du Lac Antimycobacterial agents
JP2004512810A (en) 1999-08-31 2004-04-30 サーナ・セラピューティクス・インコーポレイテッド Modulators of gene expression based on nucleic acids
GB9928248D0 (en) 1999-12-01 2000-01-26 Gill Steven S An implantable guide tube for neurosurgery
US6310048B1 (en) 1999-12-09 2001-10-30 St. Louis University Antisense modulation of amyloid beta protein expression
US6461989B1 (en) 1999-12-22 2002-10-08 Drexel University Process for forming 312 phase materials and process for sintering the same
US20030092003A1 (en) 1999-12-29 2003-05-15 Ribozyme Pharmaceuticals, Inc. Method and reagent for the treatment of Alzheimer's disease
US20050229272A1 (en) 1999-12-30 2005-10-13 Monica Driscoll Compositions and methods for gene silencing
US20050032733A1 (en) 2001-05-18 2005-02-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA)
US20070026394A1 (en) * 2000-02-11 2007-02-01 Lawrence Blatt Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies
US7276643B2 (en) 2000-02-18 2007-10-02 The Regents Of The University Of California Transgenic animals, cell lines derived therefrom, and methods for screening for anti-amyloidogenic agents
MXPA02008361A (en) 2000-02-28 2004-05-17 Genesegues Inc Nanocapsule encapsulation system and method.
US6855314B1 (en) 2000-03-22 2005-02-15 The United States Of America As Represented By The Department Of Health And Human Services AAV5 vector for transducing brain cells and lung cells
US6468524B1 (en) 2000-03-22 2002-10-22 The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services AAV4 vector and uses thereof
US6945969B1 (en) 2000-03-31 2005-09-20 Medtronic, Inc. Catheter for target specific drug delivery
US6551290B1 (en) 2000-03-31 2003-04-22 Medtronic, Inc. Catheter for target specific drug delivery
GB0009887D0 (en) 2000-04-20 2000-06-07 Btg Int Ltd Cytotoxic agents
US6372250B1 (en) 2000-04-25 2002-04-16 The Regents Of The University Of California Non-invasive gene targeting to the brain
CA2410015A1 (en) 2000-05-26 2001-12-06 Thomas W. Dubensky, Jr. Methods of transducing neural cells using lentivirus vectors
US20020042388A1 (en) 2001-05-01 2002-04-11 Cooper Mark J. Lyophilizable and enhanced compacted nucleic acids
JP2004513676A (en) * 2000-06-22 2004-05-13 オースティン，サム，エル Bioadhesive composition and its production and use
US6814014B2 (en) * 2000-07-03 2004-11-09 Brother Kogyo Kabushiki Kaisha Sewing apparatus and sewing cartridge
WO2002005804A1 (en) 2000-07-19 2002-01-24 Smithkline Beecham Corporation Compounds and methods
AU2001277171A1 (en) 2000-07-26 2002-02-05 Medtronic, Inc. Catheter for target specific drug delivery
US6866859B2 (en) 2000-08-30 2005-03-15 Biocoat Incorporated Bi-laminar, hyaluronan coatings with silver-based anti-microbial properties
US20030190635A1 (en) 2002-02-20 2003-10-09 Mcswiggen James A. RNA interference mediated treatment of Alzheimer's disease using short interfering RNA
US20050209179A1 (en) 2000-08-30 2005-09-22 Sirna Therapeutics, Inc. RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA)
CA2422078C (en) 2000-09-11 2011-08-09 The Regents Of The University Of California High efficiency cardiac gene transfer
US6659995B1 (en) 2000-11-17 2003-12-09 Syde A. Taheri Autologous myocyte micro granual retrieval and implantation (AMMGRI)
CA2327208A1 (en) 2000-11-30 2002-05-30 The Government Of The United States Of America Methods of increasing distribution of therapeutic agents
DE60130583T3 (en) * 2000-12-01 2018-03-22 Europäisches Laboratorium für Molekularbiologie SMALL RNA MOLECULES TRANSFERRING RNA INTERFERENCE
WO2002063959A1 (en) 2001-02-09 2002-08-22 The Schepens Eye Research Institute Methods and compositions for stimulating axon regeneration and prventing neuronal cell degeneration
US7182944B2 (en) 2001-04-25 2007-02-27 The United States Of America As Represented By The Department Of Health And Human Services Methods of increasing distribution of nucleic acids
EP1389194A2 (en) * 2001-04-27 2004-02-18 Vertex Pharmaceuticals Incorporated Inhibitors of bace
EP1409737A4 (en) 2001-06-15 2005-10-12 Interleukin Genetics Inc Methods for detecting and treating the early onset of aging-related conditions
WO2003013437A2 (en) 2001-08-07 2003-02-20 University Of Delaware Compositions and methods for the prevention and treatment of huntington's disease
US6944497B2 (en) 2001-10-31 2005-09-13 Medtronic, Inc. System and method of treating stuttering by neuromodulation
AU2002249967A1 (en) 2001-11-12 2003-05-26 Epiclone, Inc. Gene silencing using sense dna and antisense rna hybrid constructs
US20030105047A1 (en) 2001-11-30 2003-06-05 Medtronic, Inc. Techniques for treating neurodegenerative disorders by brain infusion of mutational vectors
US20030120327A1 (en) 2001-12-20 2003-06-26 Mark Tobritzhofer Medical lead adaptor assembly with retainer
US20030120282A1 (en) * 2001-12-24 2003-06-26 Scouten Charles W. Stereotaxic manipulator with retrofitted linear scales and digital display device
US7294504B1 (en) 2001-12-27 2007-11-13 Allele Biotechnology & Pharmaceuticals, Inc. Methods and compositions for DNA mediated gene silencing
US7270653B2 (en) 2002-02-20 2007-09-18 Abbott Research Group Methods of treating abnormal biological conditions using metal oxides
US20050096284A1 (en) 2002-02-20 2005-05-05 Sirna Therapeutics, Inc. RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US20030224512A1 (en) 2002-05-31 2003-12-04 Isis Pharmaceuticals Inc. Antisense modulation of beta-site APP-cleaving enzyme expression
US20040023855A1 (en) 2002-04-08 2004-02-05 John Constance M. Biologic modulations with nanoparticles
AU2003228667A1 (en) 2002-04-22 2003-12-19 Sirna Therapeutics Inc. Nucleic acid mediated disruption of hiv fusogenic peptide interactions
US20040018520A1 (en) 2002-04-22 2004-01-29 James Thompson Trans-splicing enzymatic nucleic acid mediated biopharmaceutical and protein
WO2003099298A1 (en) 2002-05-24 2003-12-04 Max-Planck Gesellschaft zur Förderung der Wissenschaften e.V. Rna interference mediating small rna molecules
CA2489174C (en) 2002-07-10 2013-02-05 Thomas Tuschl Rna-interference by single-stranded rna molecules
US7008403B1 (en) 2002-07-19 2006-03-07 Cognitive Ventures Corporation Infusion pump and method for use
EP1552749B1 (en) 2002-07-25 2013-03-27 Nissei Kabushiki Kaisha Rolled cone manufacturing apparatus
US20040023390A1 (en) 2002-08-05 2004-02-05 Davidson Beverly L. SiRNA-mediated gene silencing with viral vectors
US20050255086A1 (en) 2002-08-05 2005-11-17 Davidson Beverly L Nucleic acid silencing of Huntington's Disease gene
US20050106731A1 (en) 2002-08-05 2005-05-19 Davidson Beverly L. siRNA-mediated gene silencing with viral vectors
US20050042646A1 (en) 2002-08-05 2005-02-24 Davidson Beverly L. RNA interference suppresion of neurodegenerative diseases and methods of use thereof
US20040032733A1 (en) * 2002-08-08 2004-02-19 Gabriel Frederick V. Candle carrier for use with candle accessories burning tea light candles
US6877447B2 (en) * 2002-08-23 2005-04-12 Tuftco Corporation Double end servo scroll and direct scroll driver pattern attachment for tufting machine
US7083620B2 (en) 2002-10-30 2006-08-01 Medtronic, Inc. Electrosurgical hemostat
WO2006006948A2 (en) * 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
EP2314691A3 (en) * 2002-11-14 2012-01-18 Dharmacon, Inc. Fuctional and hyperfunctional siRNA
US20040265849A1 (en) 2002-11-22 2004-12-30 Applera Corporation Genetic polymorphisms associated with Alzheimer's disease, methods of detection and uses thereof
US7605249B2 (en) 2002-11-26 2009-10-20 Medtronic, Inc. Treatment of neurodegenerative disease through intracranial delivery of siRNA
US20050048641A1 (en) 2002-11-26 2005-03-03 Medtronic, Inc. System and method for delivering polynucleotides to the central nervous system
US7618948B2 (en) 2002-11-26 2009-11-17 Medtronic, Inc. Devices, systems and methods for improving and/or cognitive function through brain delivery of siRNA
US7829694B2 (en) * 2002-11-26 2010-11-09 Medtronic, Inc. Treatment of neurodegenerative disease through intracranial delivery of siRNA
JP2004232811A (en) 2003-01-31 2004-08-19 Hitachi Unisia Automotive Ltd Electromagnetic clutch for driving auxiliary machine
US8946151B2 (en) 2003-02-24 2015-02-03 Northern Bristol N.H.S. Trust Frenchay Hospital Method of treating Parkinson's disease in humans by convection-enhanced infusion of glial cell-line derived neurotrophic factor to the putamen
US20040186528A1 (en) 2003-03-20 2004-09-23 Medtronic, Inc. Subcutaneous implantable medical devices with anti-microbial agents for chronic release
US8512290B2 (en) 2003-03-20 2013-08-20 Boston Scientific Scimed, Inc. Devices and methods for delivering therapeutic or diagnostic agents
US20040198640A1 (en) 2003-04-02 2004-10-07 Dharmacon, Inc. Stabilized polynucleotides for use in RNA interference
EP1620133B1 (en) 2003-05-01 2015-12-09 Genzyme Corporation Gene therapy for neurometabolic disorders
US20040258666A1 (en) 2003-05-01 2004-12-23 Passini Marco A. Gene therapy for neurometabolic disorders
US7917228B2 (en) 2003-05-13 2011-03-29 Medtronic, Inc. Medical lead adaptor assembly
AU2004239114B2 (en) 2003-05-14 2008-03-13 Japan Science And Technology Agency Inhibition of the expression of huntingtin gene
US20060014165A1 (en) 2003-07-14 2006-01-19 Decode Genetics Ehf. Methods of diagnosis and treatment for asthma and other respiratory diseases based on haplotype association
ES2485848T3 (en) 2003-09-12 2014-08-14 University Of Massachusetts RNA interference for the treatment of disorders related to function gain
EP1675948A2 (en) 2003-10-23 2006-07-05 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED TREATMENT OF PARKINSON DISEASE USING SHORT INTERERING NUCLEIC ACID (siNA)
US7678780B2 (en) 2003-12-29 2010-03-16 Allan Mishra Method of treating cancer using platelet releasate
WO2005070104A2 (en) 2004-01-09 2005-08-04 The University Of Tennessee Research Foundation REAL-TIME POLYMERASE CHAIN REACTION-BASED GENOTYPING ASSAY FOR β2-ADRENERGIC RECEPTOR SINGLE NUCLEODITE POLYMORPHISM
US20050202075A1 (en) * 2004-03-12 2005-09-15 Pardridge William M. Delivery of genes encoding short hairpin RNA using receptor-specific nanocontainers
WO2005116204A1 (en) 2004-05-11 2005-12-08 Rnai Co., Ltd. Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same
WO2006022639A1 (en) 2004-07-21 2006-03-02 Applera Corporation Genetic polymorphisms associated with alzheimer's disease, methods of detection and uses thereof
US8017385B2 (en) 2004-10-22 2011-09-13 Neurologix, Inc. Use of apotosis inhibiting compounds in degenerative neurological disorders
NL1028134C2 (en) 2005-01-27 2006-07-31 Sara Lee De Nv Method for preparing a drink suitable for consumption from at least two ingredients to be dissolved and / or extracted and an amount of liquid.
TW200635542A (en) 2005-04-01 2006-10-16 Dharma Drum Mountain Method of establishing and using commemorative material
US20060257912A1 (en) 2005-05-06 2006-11-16 Medtronic, Inc. Methods and sequences to suppress primate huntington gene expression
US20080280843A1 (en) 2006-05-24 2008-11-13 Van Bilsen Paul Methods and kits for linking polymorphic sequences to expanded repeat mutations
GB0520235D0 (en) 2005-10-05 2005-11-16 Astrazeneca Ab Method
CA2627025A1 (en) 2005-10-28 2007-05-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of huntingtin gene
WO2007087451A2 (en) 2006-01-25 2007-08-02 University Of Massachusetts Compositions and methods for enhancing discriminatory rna interference
WO2008054544A2 (en) 2006-05-22 2008-05-08 Immune Disease Institute, Inc. Method for delivery across the blood brain barrier
ITRM20060289A1 (en) 2006-05-31 2007-12-01 Ranieri Cancedda BIO MEMBRANE ENGINEERED OSTEO ANGIOGENICA AND ITS USES FOR THE REGENERATION OF BONE FABRIC
EP2046993A4 (en) 2006-07-07 2010-11-17 Univ Massachusetts Rna silencing compositions and methods for the treatment of huntington's disease
US20080039415A1 (en) 2006-08-11 2008-02-14 Gregory Robert Stewart Retrograde transport of sirna and therapeutic uses to treat neurologic disorders
CN200970210Y (en) 2006-10-12 2007-11-07 王会才 Cleaning and dewatering machine for mop
WO2008143774A2 (en) 2007-05-01 2008-11-27 University Of Massachusetts Methods and compositions for locating snp heterozygosity for allele specific diagnosis and therapy

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