US5898031A — Oligoribonucleotides for cleaving RNA

Claim 1

Independent Claim 97 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit which is modified to improve the binding affinity of said compound to the preselected RNA target when compared to the binding affinity of an unmodified oligoribonucleotide to the RNA target; and a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 2

Dependent Claim 97 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit which is modified to improve the binding affinity of said compound to the preselected RNA target when compared to the binding affinity of an unmodified oligoribonucleotide to the RNA target; and a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 3

Dependent Claim 48 words

The oligomeric compound of claim 1 further comprising a third segment comprising at least one ribofuranosyl nucleoside subunit which is modified to improve the binding affinity of said compound to the preselected RNA target when compared to the binding affinity of an unmodified oligoribonucleotide to the RNA target.

Claim 4

Dependent Claim 28 words

The oligomeric compound of claim 1 which, when hybridized with said RNA target, is capable of activating a double-stranded RNAse enzyme to effect cleavage of said RNA target.

Claim 5

Dependent Claim 19 words

The oligomeric compound of claim 2 wherein said second segment is positioned between said first and said third segments.

Claim 6

Dependent Claim 19 words

The oligomeric compound of claim 2 wherein each of said first and third segments comprise at least three subunits.

Claim 7

Dependent Claim 17 words

The oligomeric compound of claim 2 wherein said second segment comprises from four to twelve nucleoside subunits.

Claim 8

Dependent Claim 17 words

The oligomeric compound of claim 6 wherein said second segment comprises from five to nine nucleoside subunits.

Claim 9

Dependent Claim 27 words

The oligomeric compound of claim 2 wherein said second segment has at least five subunits and said first and third segments each have at least three subunits.

Claim 10

Dependent Claim 16 words

The oligomeric compound of claim 8 wherein said second segment has at least seven nucleoside subunits.

Claim 11

Dependent Claim 109 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit that is modified to improve at least one of: pharmacokinetic binding, absorption, distribution or clearance properties of the compound; affinity or specificity of said compound to said target RNA; or modification of the charge of said compound as compared to unmodified compound; and a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 12

Dependent Claim 109 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit that is modified to improve at least one of: pharmacokinetic binding, absorption, distribution or clearance properties of the compound; affinity or specificity of said compound to said target RNA; or modification of the charge of said compound as compared to unmodified compound; and a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 13

Dependent Claim 60 words

The oligomeric compound of claim 10 further comprising a third segment comprising at least one ribofuranosyl nucleoside subunit that is modified to improve at least one of: pharmacokinetic binding, absorption, distribution or clearance properties of the compound; affinity or specificity of said compound to said target RNA; or modification of the charge of said compound as compared to unmodified compound.

Claim 14

Dependent Claim 28 words

The oligomeric compound of claim 10 which, when hybridized with said RNA target, is capable of activating a double-stranded RNAse enzyme to effect cleavage of said RNA target.

Claim 15

Dependent Claim 19 words

The oligomeric compound of claim 11 wherein said second segment is positioned between said first and said third segments.

Claim 16

Dependent Claim 19 words

The oligomeric compound of claim 11 wherein each of said first and third segments comprise at least three subunits.

Claim 17

Dependent Claim 17 words

The oligomeric compound of claim 11 wherein said second segment comprises from four to twelve nucleoside subunits.

Claim 18

Dependent Claim 17 words

The oligomeric compound of claim 15 wherein said second segment comprises from five to nine nucleoside subunits.

Claim 19

Dependent Claim 27 words

The oligomeric compound of claim 11 wherein said second segment has at least five subunits and said first and third segments each have at least three subunits.

Claim 20

Dependent Claim 16 words

The oligomeric compound of claim 17 wherein said second segment has at least seven nucleoside subunits.

Claim 21

Dependent Claim 87 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment having at least one 2'-O-C 1-20 alkyl, 2'-O-substituted C 1-20 alkyl or 2'-fluoro modified ribofuranosyl nucleoside subunit where the substitution on said alkyl is amino, hydroxy or C 1-10 alkyl ether modification; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages that are stable to degradation as compared to phosphodiester bonds.

Claim 22

Dependent Claim 87 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment having at least one 2'-O-C 1-20 alkyl, 2'-O-substituted C 1-20 alkyl or 2'-fluoro modified ribofuranosyl nucleoside subunit where the substitution on said alkyl is amino, hydroxy or C 1-10 alkyl ether modification; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages that are stable to degradation as compared to phosphodiester bonds.

Claim 23

Dependent Claim 42 words

The oligomeric compound of claim 19 further comprising a third segment comprising at least one 2'-O-C 1-20 alkyl, 2'-O-substituted C 1-20 alkyl or 2'-fluoro modified ribofuranosyl nucleoside subunit where the substitution on said alkyl is amino, hydroxy or C 1-10 alkyl ether.

Claim 24

Dependent Claim 19 words

The oligomeric compound of claim 20 wherein said second segment is positioned between said first and said third segments.

Claim 25

Dependent Claim 19 words

The oligomeric compound of claim 20 wherein each of said first and third segments comprise at least three subunits.

Claim 26

Dependent Claim 17 words

The oligomeric compound of claim 20 wherein said second segment comprises from four to twelve nucleoside subunits.

Claim 27

Dependent Claim 17 words

The oligomeric compound of claim 20 wherein said second segment comprises from five to nine nucleoside subunits.

Claim 28

Dependent Claim 27 words

The oligomeric compound of claim 20 wherein said second segment has at least five subunits and said first and third segments each have at least three subunits.

Claim 29

Dependent Claim 16 words

The oligomeric compound of claim 20 wherein said second segment has at least seven nucleoside subunits.

Claim 30

Dependent Claim 29 words

The oligomeric compound of claim 19 which, when hybridized with said RNA target, is capable of activating a double stranded RNAse enzyme to effect cleavage of said RNA target.

Claim 31

Dependent Claim 49 words

The oligomeric compound of claim 22 wherein each of said ribofuranosyl nucleoside subunits of said first and said third segments is modified to include a 2'-O-C 1-20 alkyl, 2'-O-substituted C 1-20 alkyl or 2'-fluoro and wherein the substitution on said alkyl is amino, hydroxy or C 1-10 alkyl ether.

Claim 32

Dependent Claim 46 words

The oligomeric compound of claim 19 wherein at least two of said nucleoside subunits are connected by a phosphorothioate, 3'-deoxy-3'-thio-phosphorothioate, 5'-deoxy-5'-thio-phosphorothioate, phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 5'-deoxy phosphinate, borano phosphate, 3'-deoxy-3'-amino phosphoramidate, 5'-deoxy-5'-amino phosphoramidate, hydrogen phosphonate, borano phosphate ester, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester linkage.

Claim 33

Dependent Claim 47 words

The oligomeric compound of claim 19 wherein each of the nucleoside subunits of said first segment are connected by phosphorothioate, 3'-deoxy-3'-thio-phosphorothioate, 5'-deoxy-5'-thio-phosphorothioate, phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 5'-deoxy phosphinate, borano phosphate, 3'-deoxy-3'-amino phosphoramidate, 5'-deoxy-5'-amino phosphoramidate, hydrogen phosphonate, borano phosphate ester, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester linkages.

Claim 34

Dependent Claim 21 words

The oligomeric compound of claim 19 wherein each of said nucleoside subunits of said first segment are connected by phosphorothioate linkages.

Claim 35

Dependent Claim 21 words

The oligomeric compound of claim 19 wherein each of said nucleoside subunits of said second segment are connected by phosphorothioate linkages.

Claim 36

Dependent Claim 47 words

The oligomeric compound of claim 20 wherein each of said nucleoside subunits of said third segment are connected by phosphorothioate, 3'-deoxy-3'-thio-phosphorothioate, 5'-deoxy-5'-thio-phosphorothioate, phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 5'-deoxy phosphinate, borano phosphate, 3'-deoxy-3'-amino phosphoramidate, 5'-deoxy-5'-amino phosphoramidate, hydrogen phosphonate, borano phosphate ester, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester linkages.

Claim 37

Dependent Claim 21 words

The oligomeric compound of claim 20 wherein each of said nucleoside subunits of said third segment are connected by phosphorothioate linkages.

Claim 38

Dependent Claim 26 words

The oligomeric compound of claim 20 wherein each of said nucleoside subunits of said first, said second and said third subunits are connected by phosphorothioate linkages.

Claim 39

Dependent Claim 36 words

The oligomeric compound of claim 19 wherein each of the nucleoside subunits of said first segment are connected by carbonate, carbamate, silyl, sulfur, sulfonate, sulfonamide, formacetal, thioformacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo, methylenedimethylhydrazo, methyleneoxymethylimino or methylenecarbonylamino linkages.

Claim 40

Dependent Claim 36 words

The oligomeric compound of claim 20 wherein each of the nucleoside subunits of said third segment are connected by carbonate, carbamate, silyl, sulfur, sulfonate, sulfonamide, formacetal, thioformacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo, methylenedimethylhydrazo, methyleneoxymethylimino or methylenecarbonylamino linkages.

Claim 41

Dependent Claim 117 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA comprising at least twelve ribofuranosyl nucleosides in a sequence; said nucleoside subunits being joined by internucleoside bonds which are more stable to degradation as compared to phosphodiester bonds; the compound having two wing portions interspaced by a gap portion; the wing portions each comprising at least one modified nucleoside subunit, which modified nucleoside subunit is modified to improve at least one of: pharmacokinetic binding, absorption, distribution or clearance properties of the compound; affinity or specificity of said compound to said target RNA; or modification of the charge of said compound as compared to unmodified compound; the gap portion having at least four consecutive ribonucleoside subunits.

Claim 42

Dependent Claim 117 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA comprising at least twelve ribofuranosyl nucleosides in a sequence; said nucleoside subunits being joined by internucleoside bonds which are more stable to degradation as compared to phosphodiester bonds; the compound having two wing portions interspaced by a gap portion; the wing portions each comprising at least one modified nucleoside subunit, which modified nucleoside subunit is modified to improve at least one of: pharmacokinetic binding, absorption, distribution or clearance properties of the compound; affinity or specificity of said compound to said target RNA; or modification of the charge of said compound as compared to unmodified compound; the gap portion having at least four consecutive ribonucleoside subunits.

Claim 43

Dependent Claim 17 words

The oligomeric compound of claim 38 wherein said gap portion has at least five consecutive ribonucleoside subunits.

Claim 44

Dependent Claim 52 words

A synthetic oligomeric compound comprising, in sequence; a first segment having a plurality of 2'-O-alkyl nucleoside subunits; a second segment having at least four consecutive 2'-hydroxyl ribonucleoside subunits; and a third segment having a plurality of 2'-O-alkyl nucleoside subunits; and the nucleoside subunits of the oligomer being joined by phosphorothioate internucleoside linkages.

Claim 45

Dependent Claim 52 words

A synthetic oligomeric compound comprising, in sequence; a first segment having a plurality of 2'-O-alkyl nucleoside subunits; a second segment having at least four consecutive 2'-hydroxyl ribonucleoside subunits; and a third segment having a plurality of 2'-O-alkyl nucleoside subunits; and the nucleoside subunits of the oligomer being joined by phosphorothioate internucleoside linkages.

Claim 46

Dependent Claim 18 words

The oligomeric compound of claim 40 wherein said second segment has at least five consecutive 2'-hydroxyl ribonucleotide subunits.

Claim 47

Dependent Claim 16 words

The oligomeric compound of claim 40 wherein said oligomer is specifically hybridizable with a preselected RNA.

Claim 48

Dependent Claim 31 words

A method for in vitro modification of a sequence-specific target RNA comprising contacting a test solution containing a dsRNase enzyme and said target RNA with an oligomeric compound of claim 1.

Claim 49

Dependent Claim 50 words

The method of claim 43 wherein said oligomeric compound further comprises a third segment comprising at least one ribofuranosyl nucleoside subunit which is modified to improve the binding affinity of said compound to the RNA target when compared to the binding affinity of an unmodified oligoribonucleotide to the RNA target.

Claim 50

Dependent Claim 18 words

The method of claim 44 wherein said second segment is positioned between said first and said third segments.

Claim 51

Dependent Claim 16 words

The method of claim 44 wherein said second segment comprises from four to twelve nucleoside subunits.

Claim 52

Dependent Claim 26 words

The method of claim 44 wherein said second segment has at least five subunits and said first and third segments each have at least three subunits.

Claim 53

Dependent Claim 67 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least one surrogate nucleoside subunit; a second segment comprising at least four ribofuranosyl nucleoside subunits located in a consecutive sequence and having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages that are stable to degradation as compared to phosphodiester bonds.

Claim 54

Dependent Claim 67 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least one surrogate nucleoside subunit; a second segment comprising at least four ribofuranosyl nucleoside subunits located in a consecutive sequence and having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages that are stable to degradation as compared to phosphodiester bonds.

Claim 55

Dependent Claim 17 words

The oligomeric compound of claim 48 wherein said surrogate nucleoside subunit is a peptide nucleic acid subunit.

Claim 56

Dependent Claim 16 words

The oligomeric compound of claim 48 wherein said surrogate nucleoside subunit is a morpholino nucleoside subunit.

Claim 57

Dependent Claim 15 words

The oligomeric compound of claim of 48 wherein said surrogate nucleoside is a cyclobutyl nucleoside.

Claim 58

Dependent Claim 14 words

The oligomeric compound of claim 48 wherein said surrogate nucleoside is a pyrrolidine nucleoside.

Claim 59

Dependent Claim 74 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least two nucleoside subunits; said nucleoside subunits of said first segment being connected by non-phosphorus internucleoside linkages; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said second segment being connected by internucleoside linkages that are stable to degradation as compared to phosphodiester bonds.

Claim 60

Dependent Claim 74 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least two nucleoside subunits; said nucleoside subunits of said first segment being connected by non-phosphorus internucleoside linkages; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said second segment being connected by internucleoside linkages that are stable to degradation as compared to phosphodiester bonds.

Claim 61

Dependent Claim 29 words

The oligomeric compound of claim 53 wherein said non-phosphorous linkages are carbonate, carbamate, silyl, sulfur, sulfonate, sulfonamide, formacetal, thioformacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo, methylenedimethylhydrazo or methyleneoxymethylimino, methylenecarbonylamino internucleoside linkages.

Claim 62

Dependent Claim 21 words

The oligomeric compound of claim 53 wherein said non-phosphorus internucleoside linkages are formacetal, thioformacetal, methylenemethylimino, methylenedimethylhydrazo, methyleneoxymethylimino or methylenecarbonylamino internucleoside linkages.

Claim 63

Dependent Claim 19 words

The oligomeric compound of claim 53 said nucleoside subunits of said second segment being connected by phosphorothioate internucleoside linkages.

Claim 64

Dependent Claim 77 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least three nucleoside subunits; said nucleoside subunits of said first segment being connected by alternating phosphorus, non-phosphorus internucleoside linkages; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said second segment being connected by internucleoside linkages that are more stable to degradation as compared to phosphodiester bonds.

Claim 65

Dependent Claim 77 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least three nucleoside subunits; said nucleoside subunits of said first segment being connected by alternating phosphorus, non-phosphorus internucleoside linkages; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said second segment being connected by internucleoside linkages that are more stable to degradation as compared to phosphodiester bonds.

Claim 66

Dependent Claim 29 words

The oligomeric compound of claim 57 wherein said non-phosphorous linkages are carbonate, carbamate, silyl, sulfur, sulfonate, sulfonamide, formacetal, thioformacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo, methylenedimethylhydrazo or methyleneoxymethylimino, methylenecarbonylamino internucleoside linkages.

Claim 67

Dependent Claim 21 words

The oligomeric compound of claim 57 wherein said non-phosphorus internucleoside linkages are formacetal, thioformacetal, methylenemethylimino, methylenedimethylhydrazo, methyleneoxymethylimino or methylenecarbonylamino internucleoside linkages.

Claim 68

Dependent Claim 20 words

The oligomeric compound of claim 57 wherein said nucleoside subunits of said second segment are connected by phosphorothioate internucleoside linkages.

Claim 69

Dependent Claim 101 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least two nucleoside subunits; said nucleoside subunits of said first segment being connected by 3'-deoxy-3'-thio-phosphorothioate, 5'-deoxy-5'-thio-phosphorothioate, phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 5'-deoxy phosphinate, borano phosphate, 3'-deoxy-3'-amino phosphoramidate, 5'-deoxy-5'-amino phosphoramidate, hydrogen phosphonate, borano phosphate ester, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester phosphate linkages; and a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said second segment being connected by internucleoside linkages that are more stable to degradation as compared to phosphodiester bonds.

Claim 70

Dependent Claim 101 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target comprising; a first segment including at least two nucleoside subunits; said nucleoside subunits of said first segment being connected by 3'-deoxy-3'-thio-phosphorothioate, 5'-deoxy-5'-thio-phosphorothioate, phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 5'-deoxy phosphinate, borano phosphate, 3'-deoxy-3'-amino phosphoramidate, 5'-deoxy-5'-amino phosphoramidate, hydrogen phosphonate, borano phosphate ester, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester phosphate linkages; and a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; and said nucleoside subunits of said second segment being connected by internucleoside linkages that are more stable to degradation as compared to phosphodiester bonds.

Claim 71

Dependent Claim 53 words

The oligomeric compound of claim 61 including a third segment of at least two nucleoside subunits, said nucleoside subunits of said third segment connected by 3'-deoxy-3'-thio-phosphorothioate, 5'-deoxy-5'-thio-phosphorothioate, phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 5'-deoxy phosphinate, borano phosphate, 3'-deoxy-3'-amino phosphoramidate, 5'-deoxy-5'-amino phosphoramidate, hydrogen phosphonate, borano phosphate ester, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester phosphate linkages.

Claim 72

Dependent Claim 34 words

The oligomeric compound of claim 61 wherein said nucleoside subunits of said first and third segments are connected by phosphorodithioate, phosphoroselenate, 3'-deoxy phosphinate, 3'-deoxy-3'-amino phosphoramidate, phosphoramidate, alkyl phosphonate, aryl phosphonate or phosphotriester phosphate linkages.

Claim 73

Dependent Claim 77 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit that is not a DNA or RNA major building block nucleoside; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 74

Dependent Claim 77 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit that is not a DNA or RNA major building block nucleoside; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 75

Dependent Claim 74 words

The compound of claim 64 wherein said first segment nucleoside subunit is selected from nucleosides having xanthine, hypoxanthine, 2-aminoadenine, 6-alkyl derivatives of adenine and guanine, 2-alkyl derivatives of adenine and guanine, 7-alkyl derivatives of adenine and guanine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 2 thio uracil and cytosine, 8-halo, amino, thiol, thioalkyl, hydroxyl adenine and guanine, and 5-trifluoromethyl uracil and cytosine, as their heterocyclic base.

Claim 76

Dependent Claim 81 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit excluding the nucleoside group consisting of adenosine, 2'-deoxyadenosine, guanosine, 2'-deoxyguanosine, cytidine, 2'-deoxycytidine, uridine and 2'-deoxythymidine; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Claim 77

Dependent Claim 81 words

A synthetic oligomeric compound which is specifically hybridizable with a preselected RNA target and comprises; a first segment having at least one ribofuranosyl nucleoside subunit excluding the nucleoside group consisting of adenosine, 2'-deoxyadenosine, guanosine, 2'-deoxyguanosine, cytidine, 2'-deoxycytidine, uridine and 2'-deoxythymidine; a second segment comprising at least four consecutive ribofuranosyl nucleoside subunits having 2'-hydroxyl moieties thereon; said nucleoside subunits of said oligomeric compound being connected by internucleoside linkages which are modified to stabilize said linkages from degradation as compared to phosphodiester linkages.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2002-04-26	2002-10-26	2003-04-27	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2006-04-26	2006-10-26	2007-04-27	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2010-04-26	2010-10-26	2011-04-27	$7700.00	Window Closed / Lapsed

Oligoribonucleotides for cleaving RNA

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