Oligomeric compounds comprising tricyclic nucelosides and methods for their use
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A01N-043/04
A61K-031/70
C07H-019/10
A61K-031/712
A61K-031/7125
C07H-021/04
출원번호
US-0848623
(2013-03-21)
등록번호
US-8993528
(2015-03-31)
발명자
/ 주소
Swayze, Eric E.
Siwkowski, Andrew M.
Seth, Punit P.
Prakash, Thazha P.
출원인 / 주소
Isis Pharmaceuticals, Inc.
대리인 / 주소
Isis Pharmaceuticals, Inc. Patent Dept.
인용정보
피인용 횟수 :
1인용 특허 :
125
초록▼
The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds
The present disclosure provides tricyclic nucleosides, oligomeric compounds comprising at least one of the tricyclic nucleosides and methods of using the oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
대표청구항▼
1. An oligomeric compound comprising at least one tricyclic nucleoside having formula II: wherein independently for each of said tricyclic nucleosides having formula II: Bx is a heterocyclic base moiety;one of T1 and T2 is an internucleoside linking group attaching said tricyclic nucleoside of form
1. An oligomeric compound comprising at least one tricyclic nucleoside having formula II: wherein independently for each of said tricyclic nucleosides having formula II: Bx is a heterocyclic base moiety;one of T1 and T2 is an internucleoside linking group attaching said tricyclic nucleoside of formula II to said oligomeric compound and the other of T1 and T2 is hydroxyl, a protected hydroxyl, a phosphate moiety, a 5′ or 3′-terminal group or an internucleoside linking group attaching said tricyclic nucleoside of formula II to said oligomeric compound;q1, q2, q3 and q4 are each, independently, H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl;z1 and z2 are each, independently, halogen, C1-C6 alkyl, O—C1-C6 alkyl, O—C2-C6 alkenyl, O—C2-C6 alkynyl, substituted C1-C6 alkyl, substituted O—C1-C6 alkyl, substituted O—C2-C6 alkenyl or substituted O—C2-C6 alkynyl;wherein each substituted group is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, N3, CN, OE1, N(E1)(E2), O—N(E1)(E2), C(═O)N(E1)(E2), C(═O)—N(E3)-(CH2)r—N(E1)(E2) and CH2—N(H)—C(═NE3)[N(E1)(E2)] wherein each E1, E2 and E3 is, independently, H, C1-C6 alkyl or a protecting group and r is from 2 to about 6; andwherein said oligomeric compound comprises from about 8 to about 40 linked monomeric subunits and is complementary to at least a portion of a target RNA; andwherein at least one of q1, q2, q3, q4, z1 and z2 is other than H. 2. The oligomeric compound of claim 1 wherein q3 and q4 are H for each of said tricyclic nucleosides having formula II. 3. The oligomeric compound of claim 1 wherein at least one of q1, q2, q3 and q4 is other than H for each of said tricyclic nucleosides having formula II. 4. The oligomeric compound of claim 1 wherein at least one of q1, q2, q3 and q4 is fluoro for each of said tricyclic nucleosides having formula II. 5. The oligomeric compound of claim 1 wherein at least one of q1 and q2 is fluoro for each of said tricyclic nucleosides having formula II. 6. The oligomeric compound of claim 1 wherein at least one of q3 and q4 is fluoro for each of said tricyclic nucleosides having formula II. 7. The oligomeric compound of claim 1 wherein q1 and q2 are each fluoro for each of said tricyclic nucleosides having formula II. 8. The oligomeric compound of claim 2 wherein at least one of q1, q2, q3 and q4 is C1-C6 alkyl for each of said tricyclic nucleosides having formula II. 9. The oligomeric compound of claim 8 wherein at least one of q1, q2, q3 and q4 is methyl for each of said tricyclic nucleosides having formula II. 10. The oligomeric compound of claim 1 wherein each q1, q2, q3 and q4 is H. 11. The oligomeric compound of claim 10 wherein z1 is fluoro for each of said tricyclic nucleosides having formula II. 12. The oligomeric compound of claim 10 wherein z2 is fluoro for each of said tricyclic nucleosides having formula II. 13. The oligomeric compound of claim 1 wherein z1 and z2 are each fluoro for each of said tricyclic nucleosides having formula II. 14. The oligomeric compound of claim 1, wherein at least one of z1 and z2 is O—C1-C6 alkyl or substituted O—C1-C6 alkyl for each of said tricyclic nucleosides having formula II. 15. The oligomeric compound of claim 1 wherein each internucleoside linking group is, independently, a phosphodiester or a phosphorothioate. 16. The oligomeric compound of claim 1 wherein each internucleoside linking group is a phosphorothioate. 17. A tricyclic nucleoside having formula III: wherein: Bx is a heterocyclic base moiety;one of T3 and T4 is H or a hydroxyl protecting group and the other of T3 and T4 is H, a hydroxyl protecting group or a reactive phosphorus group;q1, q2, q3 and q4 are each, independently, H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl;z1 and z2 are each, independently, halogen, C1-C6 alkyl, O—C1-C6 alkyl, O—C2-C6 alkenyl, O—C2-C6 alkynyl, substituted C1-C6 alkyl, substituted O—C1-C6 alkyl, substituted O—C2-C6 alkenyl or substituted O—C2-C6 alkynyl;wherein each substituted group is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, N3, CN, OE1, N(E1)(E2), O—N(E1)(E2), C(═O)N(E1)(E2), C(═O)—N(E3)-(CH2)r—N(E1)(E2) and CH2—N(H)—C(═NE3)[N(E1)(E2)] wherein each E1, E2 and E3 is, independently, H, C1-C6 alkyl or a protecting group and r is from 2 to about 6; andwherein at least one of q1, q2, q3, q4, z1 and z2 is other than H. 18. The tricyclic nucleoside of claim 17 wherein at least one of q1, q2, q3 and q4 is other than H. 19. A method comprising contacting a cell with an oligomeric compound, wherein said oligomeric compound comprises at least one region of at least 2 contiguous β-D-2′-deoxyribonucleosides and at least one region of from 1 to about 5 contiguous tricyclic nucleosides wherein each tricyclic nucleoside has formula II: wherein independently for each of said tricyclic nucleosides having formula II: Bx is a heterocyclic base moiety;one of T1 and T2 is an internucleoside linking group attaching said tricyclic nucleoside of formula II to said oligomeric compound and the other of T1 and T2 is hydroxyl, a protected hydroxyl, a phosphate moiety, a 5′ or 3′-terminal group or an internucleoside linking group attaching said tricyclic nucleoside of formula II to said oligomeric compound;q1, q2, q3 and q4 are each, independently, H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl;z1 and z2 are each, independently, halogen, C1-C6 alkyl, O—C1-C6 alkyl, O—C2-C6 alkenyl, O—C2-C6 alkynyl, substituted C1-C6 alkyl, substituted O—C1-C6 alkyl, substituted O—C2-C6 alkenyl or substituted O—C2-C6 alkynyl;wherein each substituted group is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, N3, CN, OE1, N(E1)(E2), O—N(E1)(E2), C(═O)N(E1)(E2), C(═O)—N(E3)-(CH2)r—N(E1)(E2) and CH2—N(H)—C(═NE3)[N(E1)(E2)] wherein each E1, E2 and E3 is, independently, H, C1-C6 alkyl or a protecting group and r is from 2 to about 6; andwherein said oligomeric compound comprises from about 8 to about 40 linked monomeric subunits and is complementary to at least a portion of a target RNA. 20. The method of claim 19 wherein q3 and q4 are H for each of said tricyclic nucleosides having formula II.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (125)
Tkachuk Zenovy (Kiev SUX) Kvasyuk Eugeny (Kiev SUX) Matsuka Gennady (Kiev SUX) Mikhailopulo Igor (Kiev SUX), (2′-5′) oligoadenylate analogues useful as inhibitors of host-v5.-graft response.
Huynh Dinh Tam (Croissy/Seine FRX) Gouyette Catherine (Vanves FRX) Igolen Jean (Le Mesnil St. Denis FRX), 2,N6-disubstituted and 2,N6-trisubstituted adenosine-3′-phosphoramidites.
Suhadolnik Robert J. (Roslyn PA) Pfleiderer Wolfgang (Constance DEX), 2′,5′-phosphorothioate oligoadenylates and their covalent conjugates with polylysine.
Cook Philip D. (Carlsbad CA) Delecki Daniel J. (Radnor PA) Guinosso Charles (Vista CA), Acyclic nucleoside analogs and oligonucleotide sequences containing them.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR) Stirchak Eugene P. (Corvallis OR), Alpha-morpholino ribonucleoside derivatives and polymers thereof.
Sanghvi Yogesh S. (Carlsbad CA) Cook Phillip D. (Carlsbad CA), Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling.
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.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Ramsay Shaw Barbara (Durham NC), Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same.
Altmann Karl-Heinz (Basel CHX) Imwinkelried Rene (Brig-Glis CHX) Eschenmoser Albert (Kusnacht CHX), Carbocyclic nucleosides containing bicyclic rings, oligonucleotides therefrom, process for their preparation, their use.
Altmann Karl-Heinz (Basel CHX) Imwinkelried Rene (Brig-Glis CHX) Eschenmoser Albert (Kusnacht CHX), Carbocyclic nucleosides containing bicyclic rings, oligonucleotides therefrom, process for their preparation, their use.
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.
Froehler Brian (Belmont CA) Matteucci Mark (Burlingame CA), Enhanced triple-helix and double-helix formation with oligomers containing modified purines.
Froehler Brian (Belmont CA) Wagner Rick (Belmont CA) Matteucci Mark (Burlingame CA) Jones Robert J. (Millbrae CA) Gutierrez Arnold J. (Sandy Lane CA) Pudlo Jeff (Burlingame CA), Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines.
Rogers Thomas E. (Manchester MO) Gray Steven H. (Ellisville MO) Devadas Balekudru (Chesterfield MO) Adams Steven P. (St. Charles MO), Improved probes using nucleosides containing 3-dezauracil analogs.
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.
Benner Steven A. (Hadlaubstrasse 151 CH-8006 Zurich CHX), Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases.
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.
Froehler Brian ; Wagner Rick ; Matteucci Mark ; Jones Robert J. ; Gutierrez Arnold J. ; Pudlo Jeff, Methods of using oligomers containing modified pyrimidines.
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.
Cook Philip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA), Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression.
Swaminathan Sundaramoorthi ; Matteucci Mark ; Jones Robert J. ; Pudlo Jeff ; Munger John, Nuclease stable and binding competent oligomers and methods for their use.
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.
Buhr Chris (Daly City CA) Matteucci Mark (Burlingame CA) Bischofberger Norbert W. (San Carlos CA) Froehler Brian (Belmont CA), Nucleoside 5′-methylene phosphonates.
Froehler Brian C. (Belmont CA) Buhr Chris A. (Daly City CA), Nucleoside hydrogen phosphonodithioate diesters and activated phosphonodithioate analogues.
Baxter Anthony D. (Northwich GB2) Baylis Eric K. (Stockport GB2) Collingwood Stephen P. (Westhoughton GB2) Taylor Roger J. (Stretford GB2) Mesmaeker Alain (Kanerkinden CHX) Schmit Chantal (Basel CHX), Nucleoside phosphinate compounds and compositions.
Meyer ; Jr. Rich B. (Woodinville WA) Adams A. David (Snohomish WA) Petrie Charles R. (Woodinville WA), Oligo (aa
상세보기
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.
Smith Lloyd M. (South Pasadena CA) Fung Steven (Palo Alto CA) Kaiser ; Jr. Robert J. (Glendale CA), Oligonucleotides possessing a primary amino group in the terminal nucleotide.
Lebleu Bernard (Montpellier FRX) Bayard Bernard (Castelnau Le Lez FRX), Oligonucleotides with modified phosphate and modified carbohydrate moieties at the respective chain termini.
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.
Misiura Konrad (Lodz PLX) Gait Michael (Cambridge GB3), Phosphoramidite derivatives, their preparation and the use thereof in the incorporation of reporter groups on synthetic.
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.
Urdea Michael S. (Alamo CA) Horn Thomas (Berkeley CA), Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Ramsay Shaw Barbara (Durham NC), Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates.
Hawkins Mary E. (Potomac MD) Pfleiderer Wolfgang (Konstanz MD DEX) Davis Michael D. (Rockville MD) Balis Frank (Bethesda MD), Pteridine nucleotide analogs as fluorescent DNA probes.
Van Ness Jeffrey (Bothell WA) Petrie Charles R. (Woodinville WA) Tabone John C. (Bothell WA) Vermeulen Nicolaas M. J. (Woodinville WA), Solid supports for nucleic acid hybridization assays.
Cook Phillip Dan (Carlsbad CA) Manoharan Muthiah (Carlsbad CA) Ramasamy Kanda S. (Laguna Hills CA), Substituted purines and oligonucleotide cross-linking.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR), Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.