WO2006006948A3 - METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY - Google Patents

METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY Download PDF

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Publication number
WO2006006948A3
WO2006006948A3 PCT/US2004/014885 US2004014885W WO2006006948A3 WO 2006006948 A3 WO2006006948 A3 WO 2006006948A3 US 2004014885 W US2004014885 W US 2004014885W WO 2006006948 A3 WO2006006948 A3 WO 2006006948A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
compositions
improved functionality
selecting sirna
sirnas
Prior art date
Application number
PCT/US2004/014885
Other languages
French (fr)
Other versions
WO2006006948A2 (en
Inventor
Devin Leake
Angela Reynolds
Anastasia Khvorova
William Marshall
Yuriy Fedorov
Steven Read
Original Assignee
Dharmacon Inc
Devin Leake
Angela Reynolds
Anastasia Khvorova
William Marshall
Yuriy Fedorov
Steven Read
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
Priority claimed from US10/714,333 external-priority patent/US8090542B2/en
Application filed by Dharmacon Inc, Devin Leake, Angela Reynolds, Anastasia Khvorova, William Marshall, Yuriy Fedorov, Steven Read filed Critical Dharmacon Inc
Priority to PCT/US2004/014885 priority Critical patent/WO2006006948A2/en
Priority to US10/940,892 priority patent/US20120052487A9/en
Publication of WO2006006948A2 publication Critical patent/WO2006006948A2/en
Priority to US11/593,100 priority patent/US7615541B2/en
Priority to US11/594,666 priority patent/US20070128641A1/en
Priority to US11/594,530 priority patent/US7608706B2/en
Priority to US11/595,698 priority patent/US7598369B2/en
Priority to US11/598,179 priority patent/US7541453B2/en
Priority to US11/595,112 priority patent/US7605250B2/en
Priority to US11/726,245 priority patent/US20070207491A1/en
Priority to US11/729,388 priority patent/US20070185317A1/en
Priority to US11/729,924 priority patent/US20080015114A1/en
Priority to US11/731,890 priority patent/US20080045703A1/en
Priority to US11/731,894 priority patent/US7521191B2/en
Priority to US11/731,843 priority patent/US7569684B2/en
Priority to US11/731,875 priority patent/US20070299253A1/en
Priority to US11/732,457 priority patent/US7638621B2/en
Priority to US11/732,413 priority patent/US20070238868A1/en
Priority to US11/732,809 priority patent/US20070255046A1/en
Priority to US11/732,810 priority patent/US20070219362A1/en
Priority to US11/784,536 priority patent/US20070179286A1/en
Priority to US11/784,559 priority patent/US20070213520A1/en
Priority to US11/784,755 priority patent/US7550572B2/en
Priority to US11/784,756 priority patent/US20070232797A1/en
Priority to US11/784,752 priority patent/US20070213521A1/en
Priority to US11/807,530 priority patent/US20070255047A1/en
Priority to US11/807,486 priority patent/US7745610B2/en
Priority to US11/807,577 priority patent/US20070260048A1/en
Priority to US11/807,836 priority patent/US7619081B2/en
Priority claimed from US11/807,836 external-priority patent/US7619081B2/en
Priority to US11/809,909 priority patent/US20070255048A1/en
Priority to US11/810,074 priority patent/US20070276135A1/en
Priority to US11/810,382 priority patent/US20070260047A1/en
Priority to US11/810,384 priority patent/US20070260049A1/en
Priority to US11/810,383 priority patent/US7595388B2/en
Priority to US11/810,381 priority patent/US20080221316A1/en
Priority to US11/810,672 priority patent/US20070255050A1/en
Priority to US11/810,670 priority patent/US20090043084A1/en
Priority to US11/810,673 priority patent/US20070293664A1/en
Priority to US11/811,005 priority patent/US20070265437A1/en
Priority to US11/811,012 priority patent/US20070260050A1/en
Priority to US11/811,003 priority patent/US20070287833A1/en
Priority to US11/811,423 priority patent/US7645870B2/en
Priority to US11/811,424 priority patent/US20070244312A1/en
Priority to US11/811,209 priority patent/US20080085997A1/en
Priority to US11/811,925 priority patent/US20070260051A1/en
Priority to US11/811,950 priority patent/US20070260052A1/en
Priority to US11/811,954 priority patent/US20070249819A1/en
Priority to US11/811,929 priority patent/US20070255051A1/en
Priority to US11/818,555 priority patent/US7592442B2/en
Priority to US11/818,547 priority patent/US20070255052A1/en
Priority to US11/818,936 priority patent/US7598370B2/en
Priority to US11/818,938 priority patent/US7678896B2/en
Priority to US11/880,622 priority patent/US20080161547A1/en
Priority to US11/880,623 priority patent/US20090023907A1/en
Priority to US11/880,628 priority patent/US7595389B2/en
Priority to US11/880,624 priority patent/US20080027215A1/en
Priority to US11/880,794 priority patent/US7635770B2/en
Priority to US11/880,755 priority patent/US20080293595A1/en
Priority to US11/880,855 priority patent/US20080300395A1/en
Priority to US11/880,777 priority patent/US20080188648A1/en
Priority to US11/880,775 priority patent/US7655788B2/en
Priority to US11/880,776 priority patent/US20080207884A1/en
Priority to US11/881,386 priority patent/US20080221317A1/en
Priority to US11/881,385 priority patent/US20080306015A1/en
Priority to US11/880,965 priority patent/US7579458B2/en
Priority to US11/881,777 priority patent/US20090005548A1/en
Priority to US11/881,768 priority patent/US20090030190A1/en
Priority to US11/881,772 priority patent/US20080027216A1/en
Priority to US11/881,771 priority patent/US20090005547A1/en
Priority to US11/881,773 priority patent/US20090023908A1/en
Priority to US11/881,767 priority patent/US20080039617A1/en
Priority to US11/975,902 priority patent/US20080097091A1/en
Priority to US11/977,128 priority patent/US20080097092A1/en
Priority to US11/977,406 priority patent/US20090182134A1/en
Priority to US11/977,347 priority patent/US20080076908A1/en
Priority to US11/977,675 priority patent/US20080071073A1/en
Priority to US11/977,558 priority patent/US20080097089A1/en
Priority to US11/978,097 priority patent/US7638622B2/en
Priority to US11/978,107 priority patent/US7605252B2/en
Priority to US11/978,120 priority patent/US20080081904A1/en
Priority to US11/978,125 priority patent/US20080086002A1/en
Priority to US11/978,106 priority patent/US7655789B2/en
Priority to US11/978,070 priority patent/US7582746B2/en
Priority to US11/978,398 priority patent/US7709629B2/en
Priority to US11/978,455 priority patent/US7795421B2/en
Priority to US11/978,518 priority patent/US7632938B2/en
Priority to US11/978,476 priority patent/US7635771B2/en
Priority to US11/978,487 priority patent/US20080113374A1/en
Priority to US11/978,475 priority patent/US20080113372A1/en
Priority to US11/978,457 priority patent/US20080113371A1/en
Priority to US11/980,263 priority patent/US7632939B2/en
Priority to US11/980,300 priority patent/US7592443B2/en
Priority to US11/980,210 priority patent/US8198427B1/en
Priority to US11/980,102 priority patent/US7662950B2/en
Priority to US11/978,900 priority patent/US7612196B2/en
Publication of WO2006006948A3 publication Critical patent/WO2006006948A3/en
Priority to US12/157,151 priority patent/US7582747B2/en
Priority to US12/157,152 priority patent/US20080268457A1/en
Priority to US12/157,137 priority patent/US7642349B2/en
Priority to US12/157,289 priority patent/US7691998B2/en
Priority to US12/209,698 priority patent/US7977471B2/en
Priority to US12/287,757 priority patent/US7576196B2/en
Priority to US12/321,749 priority patent/US7666853B2/en
Priority to US12/322,387 priority patent/US7589191B2/en
Priority to US12/384,768 priority patent/US8030474B2/en
Priority to US12/454,055 priority patent/US20090275640A1/en
Priority to US12/454,271 priority patent/US20090227780A1/en
Priority to US12/455,098 priority patent/US7741470B2/en
Priority to US12/456,424 priority patent/US7951935B2/en
Priority to US12/459,489 priority patent/US20090291497A1/en
Priority to US12/460,876 priority patent/US20100004141A1/en
Priority to US12/462,029 priority patent/US7745612B2/en
Priority to US12/462,420 priority patent/US7737267B2/en
Priority to US12/462,776 priority patent/US20100248990A1/en
Priority to US12/462,820 priority patent/US8022198B2/en
Priority to US12/584,352 priority patent/US8222395B2/en
Priority to US12/584,850 priority patent/US7897754B2/en
Priority to US12/584,899 priority patent/US8013145B2/en
Priority to US12/586,167 priority patent/US7855186B2/en
Priority to US12/586,271 priority patent/US7781575B2/en
Priority to US12/586,999 priority patent/US20100056395A1/en
Priority to US12/589,879 priority patent/US8039610B2/en
Priority to US12/590,097 priority patent/US7816512B2/en
Priority to US12/590,252 priority patent/US7829696B2/en
Priority to US12/590,707 priority patent/US7803933B2/en
Priority to US12/592,872 priority patent/US8304528B2/en
Priority to US12/653,120 priority patent/US8022199B2/en
Priority to US12/653,402 priority patent/US7807820B2/en
Priority to US12/653,530 priority patent/US20100113307A1/en
Priority to US12/655,107 priority patent/US7833989B2/en
Priority to US12/657,448 priority patent/US8067576B2/en
Priority to US12/657,721 priority patent/US20100145039A1/en
Priority to US12/660,582 priority patent/US8247169B2/en
Priority to US12/798,603 priority patent/US8030476B2/en
Priority to US12/798,802 priority patent/US7935813B2/en
Priority to US12/798,906 priority patent/US8236942B2/en
Priority to US12/799,758 priority patent/US8217162B2/en
Priority to US12/799,975 priority patent/US20100267587A1/en
Priority to US12/802,647 priority patent/US8000902B2/en
Priority to US12/804,014 priority patent/US8071754B2/en
Priority to US12/806,320 priority patent/US7985854B2/en
Priority to US12/806,570 priority patent/US7999097B2/en
Priority to US12/807,526 priority patent/US8222396B2/en
Priority to US12/924,078 priority patent/US8268985B2/en
Priority to US12/924,653 priority patent/US8138329B2/en
Priority to US12/927,144 priority patent/US8314229B2/en
Priority to US12/928,950 priority patent/US20110105363A1/en
Priority to US13/135,336 priority patent/US8293887B2/en
Priority to US13/135,443 priority patent/US8232385B2/en
Priority to US13/136,780 priority patent/US8633306B2/en
Priority to US13/136,812 priority patent/US8426579B2/en
Priority to US13/199,001 priority patent/US20110319474A1/en
Priority to US13/199,240 priority patent/US20110319297A1/en
Priority to US13/199,946 priority patent/US20120015850A1/en
Priority to US13/317,752 priority patent/US8232386B2/en
Priority to US13/385,320 priority patent/US8461326B2/en
Priority to US13/466,631 priority patent/US8399654B2/en
Priority to US13/489,725 priority patent/US20120252873A1/en
Priority to US13/494,360 priority patent/US20120258888A1/en
Priority to US13/524,015 priority patent/US8575329B2/en
Priority to US13/531,657 priority patent/US8445667B2/en
Priority to US13/536,005 priority patent/US8445668B2/en
Priority to US13/539,630 priority patent/US20120270751A1/en
Priority to US13/542,332 priority patent/US20120283311A1/en
Priority to US13/551,794 priority patent/US8658784B2/en
Priority to US13/613,910 priority patent/US20130023446A1/en
Priority to US13/632,519 priority patent/US20130059760A1/en
Priority to US13/647,869 priority patent/US8658785B1/en
Priority to US13/764,825 priority patent/US8937172B2/en
Priority to US13/847,544 priority patent/US8883998B2/en
Priority to US13/867,175 priority patent/US20130225447A1/en
Priority to US13/867,168 priority patent/US20130225667A1/en
Priority to US14/097,551 priority patent/US9228186B2/en
Priority to US14/099,339 priority patent/US8907077B2/en
Priority to US14/936,403 priority patent/US10011836B2/en
Priority to US14/936,395 priority patent/US9839649B2/en
Priority to US14/937,607 priority patent/US9879266B2/en
Priority to US14/965,816 priority patent/US9777270B2/en
Priority to US15/254,524 priority patent/US9771586B2/en
Priority to US15/255,829 priority patent/US9719092B2/en
Priority to US15/255,973 priority patent/US9719094B2/en
Priority to US15/679,097 priority patent/US20170349904A1/en
Priority to US15/705,650 priority patent/US10233449B2/en
Priority to US15/823,415 priority patent/US10765695B2/en
Priority to US15/862,479 priority patent/US10696968B2/en
Priority to US16/038,029 priority patent/US20180320182A1/en
Priority to US16/171,166 priority patent/US10920226B2/en
Priority to US16/256,933 priority patent/US20190316139A1/en
Priority to US16/378,629 priority patent/US10421970B2/en
Priority to US16/379,273 priority patent/US20190270995A1/en
Priority to US16/680,340 priority patent/US20200123550A1/en
Priority to US16/782,976 priority patent/US11198870B2/en
Priority to US17/520,530 priority patent/US20220315922A1/en

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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C12N15/1135—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 oncogenes or tumor suppressor genes
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • 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
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/10—Applications; Uses in screening processes
    • C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active nucleic acids

Abstract

Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed.
PCT/US2004/014885 2002-11-14 2004-05-12 METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY WO2006006948A2 (en)

Priority Applications (191)

Application Number Priority Date Filing Date Title
PCT/US2004/014885 WO2006006948A2 (en) 2002-11-14 2004-05-12 METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US10/940,892 US20120052487A9 (en) 2002-11-14 2004-09-14 Methods and compositions for selecting sirna of improved functionality
US11/593,100 US7615541B2 (en) 2002-11-14 2006-11-03 siRNA targeting TIE-2
US11/594,666 US20070128641A1 (en) 2002-11-14 2006-11-08 siRNA targeting hypoxia-inducible factor 1
US11/594,530 US7608706B2 (en) 2002-11-14 2006-11-08 siRNA targeting ras-related nuclear protein
US11/595,698 US7598369B2 (en) 2002-11-14 2006-11-09 siRNA targeting histamine receptor H1
US11/598,179 US7541453B2 (en) 2002-11-14 2006-11-09 siRNA targeting aquaporin 4
US11/595,112 US7605250B2 (en) 2004-05-12 2006-11-09 siRNA targeting cAMP-specific phosphodiesterase 4D
US11/726,245 US20070207491A1 (en) 2004-05-12 2007-03-21 siRNA targeting minichromosome maintenance deficient 4 (MCM4)
US11/729,388 US20070185317A1 (en) 2002-11-14 2007-03-28 siRNA targeting HtrA serine peptidase 1
US11/729,924 US20080015114A1 (en) 2002-11-14 2007-03-29 siRNA targeting connective tissue growth factor (CTGF)
US11/731,890 US20080045703A1 (en) 2002-11-14 2007-03-30 siRNA targeting platelet-derived growth factor receptor beta polypeptide (PDGFR)
US11/731,894 US7521191B2 (en) 2002-11-14 2007-03-30 siRNA targeting connexin 43
US11/731,843 US7569684B2 (en) 2002-11-14 2007-03-30 siRNA targeting gremlin
US11/731,875 US20070299253A1 (en) 2002-11-14 2007-03-30 siRNA targeting vacuolar ATPase
US11/732,457 US7638621B2 (en) 2002-11-14 2007-04-03 siRNA targeting insulin-like growth factor 1 receptor (IGF-1R)
US11/732,413 US20070238868A1 (en) 2002-11-14 2007-04-03 siRNA targeting chemokine (C-X-C motif) receptor 4 (CXCR4)
US11/732,809 US20070255046A1 (en) 2002-11-14 2007-04-04 siRNA targeting spectrin SH3 domain binding protein 1 (SSH3BP1)
US11/732,810 US20070219362A1 (en) 2002-11-14 2007-04-04 siRNA targeting azurocidin 1 (Cartionic Antimicrobial protein 37)
US11/784,536 US20070179286A1 (en) 2002-11-14 2007-04-06 siRNA targeting testis-specific serine kinase 4
US11/784,559 US20070213520A1 (en) 2002-11-14 2007-04-06 siRNA targeting calcium/calmodulin dependent protein kinase IV (CAMK4)
US11/784,755 US7550572B2 (en) 2002-11-14 2007-04-09 siRNA targeting cell division cycle 20 homolog (CDC20)
US11/784,756 US20070232797A1 (en) 2002-11-14 2007-04-09 siRNA targeting cell division cycle 2-like 5(CDC2L5)
US11/784,752 US20070213521A1 (en) 2002-11-14 2007-04-09 siRNA targeting cell division cycle 25 (CDC25C)
US11/807,530 US20070255047A1 (en) 2002-11-14 2007-05-29 siRNA targeting cell division cycle 6 homolog (CDC6)
US11/807,486 US7745610B2 (en) 2002-11-14 2007-05-29 siRNA targeting cyclin dependent kinase 11 (CDK11)
US11/807,577 US20070260048A1 (en) 2002-11-14 2007-05-29 siRNA targeting centromere protein E, 312kDa (CENPE)
US11/807,836 US7619081B2 (en) 2002-11-14 2007-05-30 siRNA targeting coatomer protein complex, subunit beta 2 (COPB2)
US11/809,909 US20070255048A1 (en) 2002-11-14 2007-06-01 siRNA targeting discoidin domain receptor family, member 1 (DDR1)
US11/810,074 US20070276135A1 (en) 2002-11-14 2007-06-04 siRNA targeting dual specificity phosphate 5 (DUSP5)
US11/810,382 US20070260047A1 (en) 2002-11-14 2007-06-05 siRNA targeting EPH receptor A4 (EPHA4)
US11/810,384 US20070260049A1 (en) 2002-11-14 2007-06-05 siRNA targeting MAD2 mitotic arrest deficient-like (MAD2L2)
US11/810,383 US7595388B2 (en) 2002-11-14 2007-06-05 siRNA targeting EPH receptor A3 (EPHA3)
US11/810,381 US20080221316A1 (en) 2002-11-14 2007-06-05 siRNA targeting ethanolamine Kinase I1 (EKI1)
US11/810,672 US20070255050A1 (en) 2002-11-14 2007-06-06 siRNA targeting minichromosome maintenance deficient 2, mitotin (MCM2)
US11/810,670 US20090043084A1 (en) 2002-11-14 2007-06-06 siRNA targeting minichromosome maintenance deficient 3 (MCM3)
US11/810,673 US20070293664A1 (en) 2002-11-14 2007-06-06 siRNA targeting minichromosome maintenance deficient 5 (MCM5)
US11/811,005 US20070265437A1 (en) 2002-11-14 2007-06-07 siRNA targeting testes development-related NYD-SP21 (NYD-SP21)
US11/811,012 US20070260050A1 (en) 2002-11-14 2007-06-07 siRNA targeting minichromosome maintenance deficient 7 (MCM7)
US11/811,003 US20070287833A1 (en) 2002-11-14 2007-06-07 siRNA targeting minichromosome maintenance deficient 6 (MCM6)
US11/811,423 US7645870B2 (en) 2002-11-14 2007-06-08 siRNA targeting proteasome 26S subunit, non-ATPase, 10 (Gankyrin or PSMD10)
US11/811,424 US20070244312A1 (en) 2002-11-14 2007-06-08 siRNA targeting phosphoinositide-3-kinase, class 2, alpha polypeptide (PIK3C2A)
US11/811,209 US20080085997A1 (en) 2002-11-14 2007-06-08 siRNA targeting phosphoinositide-3-kinase, class 2, beta polypeptide (PIK3C2B)
US11/811,925 US20070260051A1 (en) 2002-11-14 2007-06-12 siRNA targeting pituitary tumor-transforming 1 (PTTG1)
US11/811,950 US20070260052A1 (en) 2002-11-14 2007-06-12 siRNA targeting RAD1 homolog (RAD1)
US11/811,954 US20070249819A1 (en) 2002-11-14 2007-06-12 siRNA targeting WEE1 homolog (WEE1)
US11/811,929 US20070255051A1 (en) 2002-11-14 2007-06-12 siRNA targeting serine/threonine kinase 22B (STK22B)
US11/818,555 US7592442B2 (en) 2002-11-14 2007-06-13 siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
US11/818,547 US20070255052A1 (en) 2002-11-14 2007-06-14 siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC)
US11/818,936 US7598370B2 (en) 2002-11-14 2007-06-15 siRNA targeting polo-like kinase-1 (PLK-1)
US11/818,938 US7678896B2 (en) 2002-11-14 2007-06-15 siRNA targeting serine/threonine kinase 12 (STK12 or aurora B kinase)
US11/880,622 US20080161547A1 (en) 2002-11-14 2007-07-23 siRNA targeting serine/threonine protein kinase AKT
US11/880,623 US20090023907A1 (en) 2002-11-14 2007-07-23 siRNA targeting kinesin spindle protein (KSP)
US11/880,628 US7595389B2 (en) 2002-11-14 2007-07-23 siRNA targeting casitas B cell lymphoma-B (CBL-B)
US11/880,624 US20080027215A1 (en) 2002-11-14 2007-07-23 siRNA targeting vascular endothelial growth factor (VEGF)
US11/880,794 US7635770B2 (en) 2002-11-14 2007-07-24 siRNA targeting protein kinase N-3 (PKN-3)
US11/880,755 US20080293595A1 (en) 2002-11-14 2007-07-24 siRNA targeting protein tyrosine phosphatase-1B (PTP1B)
US11/880,855 US20080300395A1 (en) 2002-11-14 2007-07-24 siRNA targeting vascular endothelial growth factor receptor 1 (VEGFR1)
US11/880,777 US20080188648A1 (en) 2002-11-14 2007-07-24 siRNA targeting human hairless protein (HR)
US11/880,775 US7655788B2 (en) 2002-11-14 2007-07-24 siRNA targeting DNA-damage-inducible transcript 4 (DDIT4)
US11/880,776 US20080207884A1 (en) 2002-11-14 2007-07-24 siRNA targeting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC)
US11/881,386 US20080221317A1 (en) 2002-11-14 2007-07-25 siRNA targeting cystic fibrosis transmembrane conductance regulator (CFTR)
US11/881,385 US20080306015A1 (en) 2002-11-14 2007-07-25 siRNA targeting proprotein convertase subtilisin/kexin type 9 (PCSK9)
US11/880,965 US7579458B2 (en) 2002-11-14 2007-07-25 siRNA targeting synuclein, alpha (SNCA-1)
US11/881,777 US20090005548A1 (en) 2002-11-14 2007-07-27 siRNA targeting nuclear receptor interacting protein 1 (NRIP1)
US11/881,768 US20090030190A1 (en) 2002-11-14 2007-07-27 siRNA targeting 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2)
US11/881,772 US20080027216A1 (en) 2002-11-14 2007-07-27 siRNA targeting sodium channel, voltage-gated, type X, alpha (SCN10A)
US11/881,771 US20090005547A1 (en) 2002-11-14 2007-07-27 siRNa targeting neuropilin 1 (NRP1)
US11/881,773 US20090023908A1 (en) 2002-11-14 2007-07-27 siRNA targeting ribosomal protein S2 (RPS2)
US11/881,767 US20080039617A1 (en) 2002-11-14 2007-07-27 siRNA targeting neuropeptide Y (NPY)
US11/975,902 US20080097091A1 (en) 2002-11-14 2007-10-22 siRNA targeting TNFalpha
US11/977,128 US20080097092A1 (en) 2002-11-14 2007-10-23 siRNA targeting kinases
US11/977,406 US20090182134A1 (en) 2002-11-14 2007-10-24 siRNA targeting phosphatases
US11/977,347 US20080076908A1 (en) 2002-11-14 2007-10-24 siRNA targeting nuclear receptors
US11/977,675 US20080071073A1 (en) 2002-11-14 2007-10-25 siRNA targeting ubiquitin ligases
US11/977,558 US20080097089A1 (en) 2002-11-14 2007-10-25 siRNA targeting deubiqutination enzymes
US11/978,097 US7638622B2 (en) 2002-11-14 2007-10-26 SiRNA targeting intercellular adhesion molecule 1 (ICAM1)
US11/978,107 US7605252B2 (en) 2002-11-14 2007-10-26 siRNA targeting kinase insert domain receptor (KDR)
US11/978,120 US20080081904A1 (en) 2002-11-14 2007-10-26 siRNA targeting carbonic anhydrase 4(CA4)
US11/978,125 US20080086002A1 (en) 2002-11-14 2007-10-26 siRNA targeting secreted frizzled-related protein 1 (sFRP1)
US11/978,106 US7655789B2 (en) 2002-11-14 2007-10-26 siRNA targeting transient receptor potential cation channel, subfamily V, member 1 (TRPV1)
US11/978,070 US7582746B2 (en) 2002-11-14 2007-10-26 siRNA targeting complement component 3 (C3)
US11/978,398 US7709629B2 (en) 2002-11-14 2007-10-29 siRNA targeting diacylglycerol O-acyltransferase homolog 2 (DGAT2)
US11/978,455 US7795421B2 (en) 2002-11-14 2007-10-29 siRNA targeting apolipoprotein B (APOB)
US11/978,518 US7632938B2 (en) 2002-11-14 2007-10-29 siRNA targeting superoxide dismutase 1 (SOD1)
US11/978,476 US7635771B2 (en) 2002-11-14 2007-10-29 siRNA targeting amyloid beta (A4) precursor protein (APP)
US11/978,487 US20080113374A1 (en) 2002-11-14 2007-10-29 siRNA targeting fructose-1,6-bisphosphatase 1 (FBP1)
US11/978,475 US20080113372A1 (en) 2002-11-14 2007-10-29 siRNA targeting glucagon receptor (GCGR)
US11/978,457 US20080113371A1 (en) 2002-11-14 2007-10-29 siRNA targeting beta secretase (BACE)
US11/980,263 US7632939B2 (en) 2002-11-14 2007-10-30 siRNA targeting proto-oncogene MET
US11/980,300 US7592443B2 (en) 2002-11-14 2007-10-30 siRNA targeting interleukin-1 receptor-associated kinase 4 (IRAK4)
US11/980,210 US8198427B1 (en) 2002-11-14 2007-10-30 SiRNA targeting catenin, beta-1 (CTNNB1)
US11/980,102 US7662950B2 (en) 2002-11-14 2007-10-30 siRNA targeting myeloid differentiation primary response gene (88) (MYD88)
US11/978,900 US7612196B2 (en) 2002-11-14 2007-10-30 siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US12/157,151 US7582747B2 (en) 2002-11-14 2008-06-06 siRNA targeting inner centromere protein antigens (INCENP)
US12/157,152 US20080268457A1 (en) 2002-11-14 2008-06-06 siRNA targeting forkhead box P3 (FOXP3)
US12/157,137 US7642349B2 (en) 2002-11-14 2008-06-06 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/157,289 US7691998B2 (en) 2002-11-14 2008-06-09 siRNA targeting nucleoporin 62kDa (Nup62)
US12/209,698 US7977471B2 (en) 2002-11-14 2008-09-12 siRNA targeting TNFα
US12/287,757 US7576196B2 (en) 2002-11-14 2008-10-14 siRNA targeting transducin (beta)-like 3 (TBL3)
US12/321,749 US7666853B2 (en) 2002-11-14 2009-01-23 siRNA targeting connective tissue growth factor (CTGF)
US12/322,387 US7589191B2 (en) 2002-11-14 2009-02-02 siRNA targeting hypoxia-inducible factor 1
US12/384,768 US8030474B2 (en) 2002-11-14 2009-04-08 siRNA targeting cyclin-dependent kinase 4 (CDK4)
US12/454,055 US20090275640A1 (en) 2002-11-14 2009-05-12 siRNA targeting inner centromere protein antigens (INCENP)
US12/454,271 US20090227780A1 (en) 2002-11-14 2009-05-14 siRNA targeting connexin 43
US12/455,098 US7741470B2 (en) 2002-11-14 2009-05-28 siRNA targeting gremlin
US12/456,424 US7951935B2 (en) 2002-11-14 2009-06-16 siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC)
US12/459,489 US20090291497A1 (en) 2002-11-14 2009-07-01 siRNA targeting transducin (beta)-like 3 (TBL3)
US12/460,876 US20100004141A1 (en) 2002-11-14 2009-07-24 siRNA targeting polo-like Kinase-1 (PLK-1)
US12/462,029 US7745612B2 (en) 2002-11-14 2009-07-28 siRNA targeting interleukin-1 receptor-associated kinase 4 (IRAK4)
US12/462,420 US7737267B2 (en) 2002-11-14 2009-08-04 siRNA targeting hypoxia-inducible factor 1
US12/462,776 US20100248990A1 (en) 2002-11-14 2009-08-07 siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
US12/462,820 US8022198B2 (en) 2002-11-14 2009-08-10 siRNA targeting histamine receptor H1
US12/584,352 US8222395B2 (en) 2002-11-14 2009-09-03 siRNA targeting kinase insert domain receptor (KDR)
US12/584,850 US7897754B2 (en) 2002-11-14 2009-09-11 SiRNA targeting ras-related nuclear protein RAN
US12/584,899 US8013145B2 (en) 2002-11-14 2009-09-14 SiRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US12/586,167 US7855186B2 (en) 2002-11-14 2009-09-17 siRNA targeting TIE-2
US12/586,271 US7781575B2 (en) 2002-11-14 2009-09-18 siRNA targeting tumor protein 53 (p53)
US12/586,999 US20100056395A1 (en) 2002-11-14 2009-09-30 siRNA targeting coatomer protein complex, subunit beta 2 (CPOB2)
US12/589,879 US8039610B2 (en) 2002-11-14 2009-10-29 siRNA targeting superoxide dismutase 1 (SOD1)
US12/590,097 US7816512B2 (en) 2002-11-14 2009-11-02 siRNA targeting proto-oncogene MET
US12/590,252 US7829696B2 (en) 2002-11-14 2009-11-04 siRNA targeting amyloid beta (A4) precursor protein (APP)
US12/590,707 US7803933B2 (en) 2002-11-14 2009-11-12 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/592,872 US8304528B2 (en) 2002-11-14 2009-12-03 SiRNA targeting fructose-1, 6-bisphosphatase 1 (FBP1)
US12/653,120 US8022199B2 (en) 2002-11-14 2009-12-08 SiRNA targeting myeloid differentiation primary response gene (88) (MYD88)
US12/653,402 US7807820B2 (en) 2002-11-14 2009-12-11 siRNA targeting beta secretase (BACE)
US12/653,530 US20100113307A1 (en) 2002-11-14 2009-12-15 siRNA targeting vascular endothelial growth factor (VEGF)
US12/655,107 US7833989B2 (en) 2002-11-14 2009-12-23 siRNA targeting connective tissue growth factor (CTGF)
US12/657,448 US8067576B2 (en) 2002-11-14 2010-01-21 siRNA targeting serine/threonine kinase 12 (STK12 or aurora B kinase)
US12/657,721 US20100145039A1 (en) 2002-11-14 2010-01-26 siRNA targeting nucleoporin 62kDa (Nup62)
US12/660,582 US8247169B2 (en) 2002-11-14 2010-03-01 SiRNA targeting diacylglycerol O-acyltransferase homolog 2 (DGAT2)
US12/798,603 US8030476B2 (en) 2002-11-14 2010-04-07 siRNA targeting gremlin
US12/798,802 US7935813B2 (en) 2002-11-14 2010-04-12 siRNA target hypoxia-inducible factor 1
US12/798,906 US8236942B2 (en) 2002-11-14 2010-04-13 SiRNA targeting glucagon receptor (GCGR)
US12/799,758 US8217162B2 (en) 2002-11-14 2010-04-30 siRNA targeting interleukin-1 receptor-associated kinase 4(IRAK4)
US12/799,975 US20100267587A1 (en) 2002-11-14 2010-05-05 siRNA targeting cyclin dependent kinase 11 (CDK11)
US12/802,647 US8000902B2 (en) 2002-11-14 2010-06-11 Methods and compositions for selecting siRNA of improved functionality
US12/804,014 US8071754B2 (en) 2002-11-14 2010-07-12 siRNA targeting apolipoprotein B (APOB)
US12/806,320 US7985854B2 (en) 2002-11-14 2010-08-10 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/806,570 US7999097B2 (en) 2002-11-14 2010-08-17 siRNA targeting beta secretase (BACE)
US12/807,526 US8222396B2 (en) 2002-11-14 2010-09-08 SiRNA targeting proto-oncogene MET
US12/924,078 US8268985B2 (en) 2002-11-14 2010-09-20 siRNA targeting amyloid beta (A4) precursor protein (APP)
US12/924,653 US8138329B2 (en) 2002-11-14 2010-10-01 siRNA targeting connective tissue growth factor (CTGF)
US12/927,144 US8314229B2 (en) 2002-11-14 2010-11-08 siRNA targeting tie-2
US12/928,950 US20110105363A1 (en) 2002-11-14 2010-12-23 siRNA targeting TNFa
US13/135,336 US8293887B2 (en) 2002-11-14 2011-07-01 SiRNA targeting beta secretase (BACE)
US13/135,443 US8232385B2 (en) 2002-11-14 2011-07-05 siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US13/136,780 US8633306B2 (en) 2002-11-14 2011-08-10 SiRNA targeting histamine receptor H1
US13/136,812 US8426579B2 (en) 2002-11-14 2011-08-11 SiRNA targeting myeloid differentiation primary response gene (88) (MYD88)
US13/199,001 US20110319474A1 (en) 2002-11-14 2011-08-17 siRNA targeting cyclin-dependent kinase 4 (CDK4)
US13/199,240 US20110319297A1 (en) 2002-11-14 2011-08-23 siRNA targeting gremlin
US13/199,946 US20120015850A1 (en) 2002-11-14 2011-09-13 siRNA targeting Superoxide
US13/317,752 US8232386B2 (en) 2002-11-14 2011-10-27 SiRNA targeting apolipoprotein B (APOB)
US13/385,320 US8461326B2 (en) 2002-11-14 2012-02-14 SiRNA targeting connective tissue growth factor (CTGF)
US13/466,631 US8399654B2 (en) 2002-11-14 2012-05-08 siRNA targeting catenin, Beat-1 (CTNNB1)
US13/489,725 US20120252873A1 (en) 2002-11-14 2012-06-06 siRNA Targeting Interleukin-1 Receptor-associated Kinase 4 (IRAK4)
US13/494,360 US20120258888A1 (en) 2002-11-14 2012-06-12 siRNA Targeting Proto-oncogene MET
US13/524,015 US8575329B2 (en) 2002-11-14 2012-06-15 siRNA targeting kinase insert domain receptor (KDR)
US13/531,657 US8445667B2 (en) 2002-11-14 2012-06-25 SiRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US13/536,005 US8445668B2 (en) 2002-11-14 2012-06-28 SiRNA targeting apolipoprotein (APOB)
US13/539,630 US20120270751A1 (en) 2002-11-14 2012-07-02 siRNA Targeting Diacylglycerol O-Acyltransferase Homolog 2 (DGAT2)
US13/542,332 US20120283311A1 (en) 2002-11-14 2012-07-05 siRNA Targeting Glucagon Receptor (GCCR)
US13/551,794 US8658784B2 (en) 2002-11-14 2012-07-18 siRNA targeting amyloid beta (A4) precursor protein (APP)
US13/613,910 US20130023446A1 (en) 2002-11-14 2012-09-13 siRNA Targeting Beta Secretase (BACE)
US13/632,519 US20130059760A1 (en) 2002-11-14 2012-10-01 siRNA Targeting Fructose-1, 6-bisphosphatase 1 (FBP1)
US13/647,869 US8658785B1 (en) 2002-11-14 2012-10-09 siRNA targeting tie-2
US13/764,825 US8937172B2 (en) 2002-11-14 2013-02-12 siRNA targeting catenin, beta-1 (CTNNB1)
US13/847,544 US8883998B2 (en) 2002-11-14 2013-03-20 siRNA targeting myeloid differentiation primary response gene (88) (MYD88)
US13/867,175 US20130225447A1 (en) 2002-11-14 2013-04-22 siRNA Targeting Apolipoprotein B (APOB)
US13/867,168 US20130225667A1 (en) 2002-11-14 2013-04-22 siRNA Targeting Cyclin-dependent Kinase Inhibitor 1B (p27, Kip1) (CDKN1B)
US14/097,551 US9228186B2 (en) 2002-11-14 2013-12-05 Methods and compositions for selecting siRNA of improved functionality
US14/099,339 US8907077B2 (en) 2002-11-14 2013-12-06 siRNA targeting TIE-2
US14/936,403 US10011836B2 (en) 2002-11-14 2015-11-09 Methods and compositions for selecting siRNA of improved functionality
US14/936,395 US9839649B2 (en) 2002-11-14 2015-11-09 Methods and compositions for selecting siRNA of improved functionality
US14/937,607 US9879266B2 (en) 2002-11-14 2015-11-10 Methods and compositions for selecting siRNA of improved functionality
US14/965,816 US9777270B2 (en) 2002-11-14 2015-12-10 Methods and compositions for selecting siRNA of improved functionality
US15/254,524 US9771586B2 (en) 2002-11-14 2016-09-01 RNAi targeting ZNF205
US15/255,829 US9719092B2 (en) 2002-11-14 2016-09-02 RNAi targeting CNTD2
US15/255,973 US9719094B2 (en) 2002-11-14 2016-09-02 RNAi targeting SEC61G
US15/679,097 US20170349904A1 (en) 2002-11-14 2017-08-16 Methods and Compositions for Selecting siRNA of Improved Functionality
US15/705,650 US10233449B2 (en) 2002-11-14 2017-09-15 Methods and compositions for selecting siRNA of improved functionality
US15/823,415 US10765695B2 (en) 2002-11-14 2017-11-27 Methods and compositions for selecting siRNA of improved functionality
US15/862,479 US10696968B2 (en) 2002-11-14 2018-01-04 Methods and compositions for selecting siRNA of improved functionality
US16/038,029 US20180320182A1 (en) 2002-11-14 2018-07-17 Methods and Compositions for Selecting siRNA of Improved Functionality
US16/171,166 US10920226B2 (en) 2002-11-14 2018-10-25 siRNA targeting LDHA
US16/256,933 US20190316139A1 (en) 2002-11-14 2019-01-24 Methods and Compositions for Selecting siRNA of Improved Functionality
US16/378,629 US10421970B2 (en) 2004-05-12 2019-04-09 Methods and compositions for selecting siRNA of improved functionality
US16/379,273 US20190270995A1 (en) 2002-11-14 2019-04-09 Methods and Compositions for Selecting siRNA of Improved Functionality
US16/680,340 US20200123550A1 (en) 2002-11-14 2019-11-11 siRNA Targeting LDHA
US16/782,976 US11198870B2 (en) 2002-11-14 2020-02-05 Methods and compositions for selecting siRNA of improved functionality
US17/520,530 US20220315922A1 (en) 2002-11-14 2021-11-05 Methods and Compositions for Selecting siRNA of Improved Functionality

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US42613702P 2002-11-14 2002-11-14
US50205003P 2003-09-10 2003-09-10
US10/714,333 US8090542B2 (en) 2002-11-14 2003-11-14 Functional and hyperfunctional siRNA
PCT/US2004/014885 WO2006006948A2 (en) 2002-11-14 2004-05-12 METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US10/940,892 US20120052487A9 (en) 2002-11-14 2004-09-14 Methods and compositions for selecting sirna of improved functionality
US11/807,836 US7619081B2 (en) 2002-11-14 2007-05-30 siRNA targeting coatomer protein complex, subunit beta 2 (COPB2)

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US11/975,902 Division US20080097091A1 (en) 2002-11-14 2007-10-22 siRNA targeting TNFalpha

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US10/714,333 Continuation-In-Part US8090542B2 (en) 2002-11-14 2003-11-14 Functional and hyperfunctional siRNA
US10/910,892 Continuation US7080829B2 (en) 2002-11-14 2004-08-04 Device for holding one end of a helical spring
US10/940,892 Continuation US20120052487A9 (en) 2002-11-14 2004-09-14 Methods and compositions for selecting sirna of improved functionality
US10/940,892 Continuation-In-Part US20120052487A9 (en) 2002-11-14 2004-09-14 Methods and compositions for selecting sirna of improved functionality
US11/593,100 Continuation-In-Part US7615541B2 (en) 2002-11-14 2006-11-03 siRNA targeting TIE-2
US11/594,530 Continuation US7608706B2 (en) 2002-11-14 2006-11-08 siRNA targeting ras-related nuclear protein
US11/594,666 Continuation US20070128641A1 (en) 2002-11-14 2006-11-08 siRNA targeting hypoxia-inducible factor 1
US11/595,698 Continuation-In-Part US7598369B2 (en) 2002-11-14 2006-11-09 siRNA targeting histamine receptor H1
US11/598,179 Continuation-In-Part US7541453B2 (en) 2002-11-14 2006-11-09 siRNA targeting aquaporin 4
US11/595,112 Continuation US7605250B2 (en) 2004-05-12 2006-11-09 siRNA targeting cAMP-specific phosphodiesterase 4D

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