Claims for Patent: 6,958,215

Summary for Patent: 6,958,215

Title:	Methods and compositions for inhibition of RNA splicing
Abstract:	A method of inhibiting the self-splicing of a Group I intron is disclosed. The method uses an oligonucleotide having a sequence essentially identical to a guide sequence found in the 5\' flanking exon and terminates with a 3\' ribonucleoside. Usually the oligonucleotide has N3\'.fwdarw.P5\' phosphoramidate or N3\'.fwdarw.P5\' thiophiosphoramidate linkages rather than phosphodiester linkages. A method of inhibiting the growth of organisms having Group I intron, particularly certain pathogenic fungi including P. carinii, C. albicans, and A. nidulans using the oglionucleotide is also provided.
Inventor(s):	Testa; Stephen M. (Lexington, KY), Disney; Matthew D. (Rochester, NY), Gryaznov; Sergei M. (San Mateo, CA), Turner; Douglas H. (Pittsford, NY)
Assignee:	Geron Corporation (Menlo Park, CA) The University of Rochester (Rochester, NY)
Application Number:	09/936,146
Patent Claims:	1. An inhibitor of a Group I intron self-splicing reaction comprising an oligonucleotide having a polynucleotide sequence that binds to a 5' internal guide sequence of a precursor RNA containing a Group I intron, or to a portion thereof, wherein said oligonucleotide binds to the 5' internal guide sequence of the precursor RNA and trans-splices to the 3' exon of the precursor RNA, and wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No:1, SEQ ID No:2, SEQ ID No:3, and SEQ ID No:9. 2. The inhibitor of claim 1 wherein said oligonucleotide comprises the polynucleotide sequence of SEQ ID No:1 and wherein said precursor RNA is a precursor ribosomal RNA from Pneumocystis carinii. 3. The inhibitor of claim 1 wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No:2, SEQ ID No:3, and SEQ ID No:9 and wherein said precursor RNA is a precursor ribosomal RNA from Candida albicans. 4. A composition comprising a suicide inhibitor of claim 1, together with a pharmaceutically acceptable carrier. 5. A method of inhibiting self-splicing of a Group I intron comprising contacting a precursor RNA containing a Group I intron with an oligonucleotide, wherein said oligonucleotide trans-splices to a 3' exon sequence of said precursor RNA and inhibits self-splicing of the Group I intron. 6. The method of claim 5 wherein said oligonucleotide comprises deoxynucleotides, ribonucleotides, or a combination thereof, and said oligonucleotide comprises a 3' terminal ribonucleoside. 7. The method of claim 5 wherein said oligonucleotide contains at least one N3'.fwdarw.P5' phosphoramidate or N3'.fwdarw.P5' thiophosphoramidate linkage. 8. The method of claim 5 wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No:1, SEQ ID No:2, SEQ ID No:3 and SEQ ID No:9. 9. The method of claim 5 wherein said oligonucleotide comprises the polynucleotide of SEQ ID No:1 and wherein said precursor RNA is a precursor ribosomal RNA from Pneumocystis carinii. 10. The method of claim 5 wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No:2, SEQ ID No:3, and SEQ ID No:9 and wherein said precursor RNA is a precursor ribosomal RNA from Candida albicans. 11. A method for inhibiting the growth of an organism transcribing a precursor RNA containing a Group I intron comprising contacting said organism with an amount of an oligonucleotide effective for growth inhibition, wherein said oligonucleotide trans-splices to a 3' exon sequence of said precursor RNA and inhibits self-splicing of the Group I intron, wherein inhibition of self-splicing of the Group I intron inhibits the growth of the organism. 12. The method of claim 11 wherein said oligonucleotide comprises deoxynucleotides, ribonucleotides, or a combination thereof, and said oligonucleotide comprises a 3' terminal ribonucleoside. 13. The method of claim 11 wherein said oligonucleotide comprises at least one N3'.fwdarw.P5' phosphoramidate or thiophosphoramidate linkage. 14. The method of claim 11 wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No: 1, SEQ ID No:2, SEQ ID No:3 and SEQ ID No:9. 15. The method of claim 11 wherein said oligonucleotide comprises the polynucleotide of SEQ ID No:1 and wherein said precursor RNA is a precursor ribosomal RNA from Pneumocystis carinii. 16. The method of claim 11 wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No:2, SEQ ID No:3, and SEQ ID No:9 and wherein said precursor RNA is a precursor ribosomal RNA from Candida albicans. 17. A method of designing an inhibitor of Group I intron splicing comprising choosing a nucleotide sequence that binds to a 5' internal guide sequence present in precursor RNA containing a Group I intron, or to a portion thereof, and preparing an oligonucleotide having the chosen sequence, wherein said oligonucleotide binds to the 5' internal guide sequence of the precursor RNA and trans-splices to the 3' exon of the precursor RNA. 18. The method of claim 17 wherein said oligonucleotide comprises deoxynucleotides, ribonucleotides, or a combination thereof, and said oligonucleotide comprises a 3' terminal ribonucleoside. 19. The method of claim 17 wherein said oligonucleotide contains at least one N3'.fwdarw.P5' phosphoramidate or thiophosphoramidate linkage.

Details for Patent 6,958,215

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2019-03-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2019-03-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2019-03-15