Antisense antiviral compound and method for treating influenza viral infection
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-048/00
C07F-009/6561
C12N-015/113
A61K-031/165
A61K-031/43
A61K-031/5377
A61K-031/545
A61K-031/7056
A61K-038/08
A61K-038/10
C07K-007/06
C07K-007/08
출원번호
US-0251124
(2014-04-11)
등록번호
US-9394323
(2016-07-19)
발명자
/ 주소
Iversen, Patrick L.
출원인 / 주소
SAREPTA THERAPEUTICS, INC.
대리인 / 주소
Seed IP Law Group PLLC
인용정보
피인용 횟수 :
0인용 특허 :
138
초록▼
The present invention relates to antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a
The present invention relates to antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. Exemplary antisense antiviral compounds are substantially uncharged, or partially positively charged, morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5′ or 3′ terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 30 bases of the 5′ or 3′ terminus of the positive sense vcRNA; c) the 45 bases surrounding the AUG start codon of an influenza viral mRNA and; d) 50 bases surrounding the splice donor or acceptor sites of influenza mRNAs subject to alternative splicing.
대표청구항▼
1. An antiviral antisense oligonucleotide consisting of the following structure: 2. The antiviral antisense oligonucleotide of claim 1, wherein the antiviral antisense oligonucleotide is conjugated to an arginine-rich polypeptide that enhances the uptake of the compound into host cells. 3. The anti
1. An antiviral antisense oligonucleotide consisting of the following structure: 2. The antiviral antisense oligonucleotide of claim 1, wherein the antiviral antisense oligonucleotide is conjugated to an arginine-rich polypeptide that enhances the uptake of the compound into host cells. 3. The antiviral antisense oligonucleotide of claim 2, wherein the arginine-rich polypeptide is any one of SEQ ID NOS:115-128. 4. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier, and an antiviral antisense oligonucleotide consisting of the following structure: 5. The pharmaceutical composition of claim 4, wherein the antiviral antisense oligonucleotide is conjugated to an arginine-rich polypeptide that enhances the uptake of the compound into host cells. 6. The pharmaceutical composition of claim 5, wherein the arginine-rich polypeptide is any one of SEQ ID NOS:115-128. 7. The pharmaceutical composition of any one of claims 4-6, further comprising an antibiotic. 8. The pharmaceutical composition of claim 7, wherein the antibiotic is bacteriostatic or bactericidal. 9. The pharmaceutical composition of claim 7, wherein the antibiotic is a beta-lactam. 10. The pharmaceutical composition of claim 7, wherein the antibiotic is selected from penicillin, amoxicillin, cephalosporin, chloramphenicol, or clindamycin. 11. The pharmaceutical composition of any one of claims 4-6, further comprising a second oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor. 12. A method of reducing replication of an Influenza A virus, comprising contacting an Influenza A virus infected cell with an antiviral antisense oligonucleotide consisting of the following structure: 13. The method of claim 12, wherein the method comprises administering the antiviral antisense oligonucleotide to a subject having an Influenza A virus infected cell. 14. The method of claim 13, further comprising administering an antibiotic in combination with the antiviral antisense oligonucleotide when the subject has a secondary bacterial infection. 15. The method of claim 14, wherein the antibiotic is administered separately from the antiviral antisense oligonucleotide. 16. The method of claim 14, wherein the antibiotic is administered concurrently with the antiviral antisense oligonucleotide. 17. The method of claim 14, wherein the antibiotic is bacteriostatic or bactericidal. 18. The method of claim 14, wherein the antibiotic is a beta-lactam. 19. The method of claim 14, wherein the antibiotic is selected from penicillin, amoxicillin, cephalosporin, chloramphenicol, or clindamycin. 20. The method of claim 14, wherein the secondary bacterial infection is a Streptococcal infection. 21. The method of claim 20, wherein the Streptococcal infection is a Streptococcus pneuomoniae infection. 22. The method of claim 12, further comprising administering a second antisense oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor separately or concurrently in combination with the antiviral antisense oligonucleotide. 23. The method of claim 22, wherein the second antisense oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor is administered separately from the antiviral antisense oligonucleotide. 24. The method of claim 22, wherein the second antisense oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor is administered concurrently with the antiviral antisense oligonucleotide. 25. The method of claim 14, further comprising administering an antisense oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor, separately or concurrently in combination with the antiviral antisense oligonucleotide. 26. The method of claim 25, wherein the second antisense oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor is administered separately from the antiviral antisense oligonucleotide. 27. The method of claim 25, wherein the second antisense oligonucleotide targeted against an RNA molecule encoding CD200 or the CD200 receptor is administered concurrently with the antiviral antisense oligonucleotide. 28. The antiviral antisense oligonucleotide of claim 1, wherein the antiviral antisense oligonucleotide is linked to a polyethylene glycol moiety. 29. The pharmaceutical composition of claim 4, wherein the antiviral antisense oligonucleotide is linked to a polyethylene glycol moiety. 30. The method of claim 12, wherein the antiviral antisense oligonucleotide is linked to a polyethylene glycol moiety. 31. The pharmaceutical composition of claim 4, further comprising an additional influenza virus-targeted therapy. 32. The pharmaceutical composition of claim 31, wherein the additional influenza virus-targeted therapy is oseltamivir phosphate. 33. The method of claim 12, further comprising administering an additional influenza virus-targeted therapy separately or concurrently in combination with the antiviral antisense oligonucleotide. 34. The method of claim 33, wherein the additional influenza virus-targeted therapy is administered concurrently with the antiviral antisense oligonucleotide. 35. The method of claim 33, wherein the additional influenza virus-targeted therapy is administered separately from the antiviral antisense oligonucleotide. 36. The method of claim 33, wherein the additional influenza virus-targeted therapy is oseltamivir phosphate.
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Suhadolnik Robert J. (Roslyn PA) Pfleiderer Wolfgang (Constance DEX), 2′,5′-phosphorothioate oligoadenylates and their covalent conjugates with polylysine.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR) Stirchak Eugene P. (Corvallis OR), Alpha-morpholino ribonucleoside derivatives and polymers thereof.
McKay Robert ; Dean Nicholas ; Monia Brett P. ; Nero Pamela S. ; Gaarde William A., Antisense oligonucleotide compositions and methods for the modulation of JNK proteins.
Cook Phillip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA) Vasseur Jean J. (San Marcos CA) Debart Francoise (Montpellier FRX), Backbone modified oligonucleotide analogues.
Sanghvi Yogesh S. (San Marcos CA) Cook Phillip D. (Vista CA), Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling.
Rothbard, Jonathan B.; Wender, Paul A.; McGrane, P. Leo; Sista, Lalitha V. S.; Kirschberg, Thorsten A., Compositions and methods for enhancing drug delivery across and into epithelial tissues.
Kevin P. Anderson ; Ronnie C. Hanecak ; Kazuya Hoshiko JP; Chikateru Nozaki JP; Tsukasa Nishihara JP; Hiroshi Nakatake JP; Fukusaburo Hamada JP; Tatsuo Eto JP; Shinichi Furukawa JP; Shoji Fu, Compositions and methods for treatment of Hepatitis C virus-associated diseases.
Iversen,Patrick L.; Moulton,Hong M.; Nelson,Michelle H.; Kroeker,Andrew D.; Stein,David A., Compositions for enhancing transport of molecules into cells.
Ohtsuka Eiko (Sappro JPX) Inoue Hideo (Sappro JPX) Morisawa Hirokazu (Kawasaki JPX) Shibahara Susumu (Kawasaki JPX) Mukai Sachiko (Kawasaki JPX) Nishihara Tohru (Kurashiki JPX), Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and st.
Baxter Anthony D. (Northwich GB2) Baylis Eric K. (Stockport GB2) Collingwood Stephen P. (Westhoughton GB2) Taylor Roger J. (Stretford GB2) De Mesmaeker Alain (Kanerkinden CHX) Schmit Chantal (Basel C, Dinucleoside phosphinates and their pharmaceutical compositions.
Kolberg Janice A. (Hercules CA) Urdea Michael S. (Alamo CA), HAV probes for use in solution phase sandwich hybridization and assays for detecting the presence of HAV.
Robbins, Paul D.; Mi, Zhibao; Frizzell, Raymond; Glorioso, Joseph C.; Gambotto, Andrea, Identication of peptides that facilitate uptake and cytoplasmic and/or nuclear transport of proteins, DNA and virues.
Agrawal Sudhir (46G Brandywine Dr. Shrewsbury MA 01545) Leiter Josef M. E. (111 Hicks St. ; #25C Brooklyn NY 11201) Palese Peter (414 Highwood Ave. Leonia NJ 07605) Zamecnik Paul C. (29 LeBeaux Dr. S, Influenza virus replication inhibiting oligonucleotide analogues and their pharmaceutical compositions.
Agrawal Sudhir (Shrewsbury MA) Leiter Josef M. E. (Brooklyn NY) Palese Peter (Leonia NJ) Zamecnik Paul C. (Shrewsbury MA), Inhibition of influenza virus replication by oligonucleotide phosphorothioates.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke She L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke She L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke Shee L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Papahadjopoulos Demetrios P. (78 Heathwood Williamsville NY 14221) Szoka ; Jr. Francis C. (375 Leroy Ave. Buffalo NY 14214), Method of encapsulating biologically active materials in lipid vesicles.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Walder Joseph A. (Iowa City IA) Walder Roxanne Y. (Iowa City IA) Eder Paul S. (Iowa City IA) Dagle John M. (Iowa City IA), Methods for blocking the expression of specifically targeted genes.
Matteucci Mark (Burlingame CA) Jones Robert J. (Daly City CA) Munger John (San Francisco CA), Modified internucleoside linkages having one nitrogen and two carbon atoms.
Ts\o Paul O. P. (2117 Folkstone Rd. Lutherville MD 21093) Miller Paul S. (225 Hopkins Rd. Baltimore MD 21212), Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof.
Walder Joseph A. (Iowa City IA) Walder Roxanne Y. (Iowa City IA), Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled.
Meyer ; Jr. Rich B. (Woodinville WA) Adams A. David (Snohomish WA) Petrie Charles R. (Woodinville WA), Oligo (aa
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Letsinger Robert L. (Wilmette IL) Gryaznov Sergei M. (San Mateo CA), Oligodeoxyribonucleotides including 3′-aminonucleoside-phosphoramidate linkages and terminal 3′-amino groups.
Bischofberger Norbert (San Carlos CA) Kent Ken (Mountain View CA) Wagner Rick (Burlingame CA) Buhr Chris (Daly City CA) Lin Kuei-Ying (Fremont CA), Oligonucleotide analogs capable of passive cell membrane permeation.
Weis Alexander Ludvik (Berwyn PA) Hausheer Frederick Herman (San Antonio TX) Chaturvedula Prasad Venkata Chala (Exton PA) Delecki Daniel Joseph (Radnor PA) Cavanaugh ; Jr. Paul Francis (West Chester , Oligonucleotide analogues containing phosphate diester linkage substitutes, compositions thereof, and precursor dinucleo.
Cook Phillip D. (San Marcos CA) Hoke Glenn (Mt. Airy MD), Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity.
Imbach Jean-Louis (Montpellier FRX) Gosselin Gilles J. M. (Montpellier FRX), Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Shaw Barbara R. (Durham NC), Oligoribonucleoside and oligodeoxyribonucleoside boranophosphates.
Maddry Joseph A. (Birmingham AL) Reynolds Robert C. (Birmingham AL) Secrist John A. (Birmingham AL) Montgomery John A. (Birmingham AL) Crooks Peter A. (Lexington KY), Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages.
Caruthers Marvin H. (Boulder CO) Marshall William S. (Boulder CO) Brill Wolfgang (Freiburg DEX) Nielsen John (Horsholm DKX), Polynucleotide phosphorodithioate.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR), Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages.
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