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- Nachgewiesen in: USPTO Patent Grants
- Sprachen: English
- Patent Number: 8,669,102
- Publication Date: March 11, 2014
- Appl. No: 13/059058
- Application Filed: August 14, 2009
- Assignees: Isis Pharmaceuticals, Inc. (Carlsbad, CA, US)
- Claim: 1. A modified antisense oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the modified antisense oligonucleotide is a gapmer and is fully complementary to an equal number of consecutive nucleobases selected from 469 to 2629 of the human PrP nucleic acid of SEQ ID NO:1.
- Claim: 2. The modified antisense oligonucleotide of claim 1 , wherein the modified oligonucleotide is a single-stranded oligonucleotide.
- Claim: 3. The modified antisense oligonucleotide of claim 2 , wherein at least one internucleoside linkage is a modified internucleoside linkage.
- Claim: 4. The modified antisense oligonucleotide of claim 3 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
- Claim: 5. The modified antisense oligonucleotide of claim 4 , wherein at least one nucleoside comprises a modified sugar.
- Claim: 6. The modified antisense oligonucleotide of claim 5 , wherein at least one modified sugar is a bicyclic sugar.
- Claim: 7. The modified antisense oligonucleotide of claim 5 , wherein at least one modified sugar is a 2 ′-O-methoxyethyl.
- Claim: 8. The modified antisense oligonucleotide of claim 2 , wherein at least one nucleoside comprises a modified nucleobase.
- Claim: 9. The modified antisense oligonucleotide of claim 8 , wherein the modified nueleobase is a 5-methylcytosine.
- Claim: 10. A method of inhibiting expression of PrP an animal, comprising administering to the animal the modified antisense oligonucleotide of claim 1 .
- Claim: 11. A modified antisense oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the modified antisense oligonucleotide is fully complementary to an equal number of consecutive nucleobases selected from 469 to 2629 of the human PrP nucleic acid of SEQ ID NO: 1.
- Claim: 12. The modified antisense oligonucleotide of claim 11 , wherein the modified oligonucleotide is a single-stranded oligonucleotide.
- Claim: 13. The modified antisense oligonucleotide of claim 12 , wherein at least one internucleoside linkage is a modified internucleoside linkage.
- Claim: 14. The modified antisense oligonucleotide of claim 13 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
- Claim: 15. The modified antisense oligonucleotide of claim 14 , wherein at least one nucleoside comprises a modified sugar.
- Claim: 16. The modified antisense oligonucleotide of claim 15 , wherein at least one modified sugar is a bicyclic sugar.
- Claim: 17. The modified antisense oligonucleotide of claim 15 , wherein at least one modified sugar is a 2 ′-O-methoxyethyl.
- Claim: 18. The modified antisense oligonucleotide of claim 12 , wherein at least one nucleoside comprises a modified nucleobase.
- Claim: 19. The modified antisense oligonucleotide of claim 18 , wherein the modified nucleohase is a 5-methylcytosine.
- Claim: 20. The modified antisense oligonucleotide of claim 6 , wherein the bicyclic sugar is a (6′S)-6′methyl BNA.
- Claim: 21. The modified antisense oligonucleotide of claim 16 , wherein the bicyclic sugar is a (6′S)-6′methyl BNA.
- Claim: 22. A method of inhibiting expression of PrP in an animal, comprising administering to the animal the modified antisense oligonucleotide of claim 11 .
- Claim: 23. The modified antisense oligonucleotide of claim 1 , wherein said modified antisense oligonucleotide consists of 15 to 30, 18 to 24, or 19 to 22 linked nucleosides.
- Claim: 24. The modified antisense oligonucleotide of claim 1 , wherein said modified antisense oligonucleotide consists of 20 linked nucleosides.
- Claim: 25. The modified antisense oligonucleotide of claim 11 , wherein said modified antisense oligonucleotide consists of 15 to 30, 18 to 24, or 19 to 22 linked nucleosides.
- Claim: 26. The modified antisense oligonucleotide of claim 11 , wherein said modified antisense oligonucleotide consists of 20 linked nucleosides.
- Claim: 27. The modified antisense oligonucleotide of claim 1 , wherein the gap segment of the oligonucleotide consists of 2-deoxynucleotides and wherein each wing segment of the oligonucleotide consists of 2-O-methoxyethyl-modified nucleotides.
- Claim: 28. The method of claim 10 , wherein the gap segment of the oligonucleotide consists of 2-deoxynucleotides and wherein each wing segment of the oligonucleotide consists of 2′-O-methoxyethyl-modified nucleotides.
- Claim: 29. The modified antisense oligonucleotide of claim 23 , wherein the gap segment of the oligonucleotide consists of 2′-deoxynucleotides and wherein each wing segment of the oligonucleotide consists of 2′-O-methoxyethyl-modified nucleotides.
- Claim: 30. The modified antisense oligonucleotide of claim 24 , wherein the gap segment of the oligonucleotide consists of 2′-deoxynucleotides and wherein each wing segment of the oligonucleotide consists of 2′-O-methoxyethyl-modified nucleotides.
- Current U.S. Class: 435/325
- Patent References Cited: 5801154 September 1998 Baracchini et al. ; 6582908 June 2003 Fodor et al. ; 7399845 July 2008 Seth et al. ; 2001/0053519 December 2001 Fodor et al. ; 2002/0081645 June 2002 Collinge ; 2003/0228597 December 2003 Cowsert et al. ; 2005/0053583 March 2005 Sakaguchi et al. ; 2006/0280745 December 2006 Collinge et al. ; 2007/0031844 February 2007 Khvorova et al. ; 2007/0123480 May 2007 Juteau et al. ; 2008/0085269 April 2008 Eisenbach-Schwartz
- Other References: Olie et al. (Biochemica et Biophysica Acta, 1576, 2002, 101-109). cited by examiner ; Branch et al., “A good antisense molecule is hard to find,” TIBS (1998) 23:45-50. cited by applicant ; Chin “On the Preparation and Utilization of Isolated and Purified Oligonucleotides” Document purportedly located on a CD-ROM and contributed to the public collection of the Katherine R. Everett Law Library of the University of North Carolina on Mar. 14, 2002. cited by applicant ; Crooke et al., “Basic Principles'of Antisense Therapeutics” Antisense Research and Application (1998) Chapter 1:1-50. cited by applicant ; Daude et al., “Specific inhibition of pathological prion protein accumulation by small interfering RNAs” Journal of Cell Science (2003) 116(13):2775-2779. cited by applicant ; Golding et al., “Suppression of prion protein in livestock by RNA interference” PNAS (2006) 103(14):5285-5290. cited by applicant ; Kapui et al., “Phosphorothioate Oligonucleotides Reduce PrPsc Levels and Prion Infectivity in Cultured Cells” Mol Med (2007) 13(3-4):190-198. cited by applicant ; Ohnishi et al., “Enhancement of Allele Discrimination by Introduction of Nucleotide Mismatches into siRNA in Allele-Specific Gene Silencing by RNAi” PLoS One (2008) 3(5):e2248. cited by applicant ; Pfeifer et al., “Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice” J. Clin. Invest. (2006) 116(12):3204-3210. cited by applicant ; Reynolds et al., “Rational siRNA design for RNA interference” Nature Biotechnology (2004) 22(3):326-330. cited by applicant ; Sanghvi et al., “Heterocyclic Base Modifications in Nucleic Acids and Their Applications in Antisense Oligonucleotides” Antisense Research and Applications (1993) pp. 273-288. cited by applicant ; Sutou et al., “Knockdown of the bovine prion gene PRNP by RNA interference (RNAi) technology” BMC Biotechnology (2007) 7:44. cited by applicant ; Tilly et al., “Efficient and specific down-regulation of prion protein expression by RNAi” Biochemical and Biophysical Research Communications (2003) 305:548-551. cited by applicant ; Weiss et al., “RNA Aptamers Specifically Interact with the Prion Protein PrP” Journal of Virology (1997) 71(11):8790-8797. cited by applicant ; White et al., “Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion diseases” PNAS (2008) 105(29):10238-10243. cited by applicant ; International Search Report for application PCT/US2009/004680 dated Oct. 13, 2009. cited by applicant
- Primary Examiner: Bowman, Amy
- Attorney, Agent or Firm: Jones Day
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