US6156501A — Arrays of modified nucleic acid probes and method…

Claim 1

Independent Claim 62 words

A composition for analyzing interactions between oligonucleotide targets and oligonucleotide probes comprising an array of a plurality of oligonucleotide analogue probes having different sequences, wherein said oligonucleotide analogue probes are coupled to a solid substrate at known locations and wherein said plurality of oligonucleotide analogue probes are selected to bind to complementary oligonucleotide targets with a similar hybridization stability across the array.

Claim 2

Dependent Claim 62 words

A composition for analyzing interactions between oligonucleotide targets and oligonucleotide probes comprising an array of a plurality of oligonucleotide analogue probes having different sequences, wherein said oligonucleotide analogue probes are coupled to a solid substrate at known locations and wherein said plurality of oligonucleotide analogue probes are selected to bind to complementary oligonucleotide targets with a similar hybridization stability across the array.

Claim 3

Dependent Claim 28 words

The composition of claim 1, wherein at least one of said oligonucleotide analogue probes is selected to maintain hybridization specificity or mismatch discrimination with said complementary oligonucleotide targets.

Claim 4

Dependent Claim 52 words

The composition of claim 1, wherein at least one of said oligonucleotide analogue probes has increased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 5

Dependent Claim 52 words

The composition of claim 1, wherein at least one of said oligonucleotide analogue probes has decreased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 6

Dependent Claim 52 words

The composition of claim 2, wherein at least one of said oligonucleotide analogue probes has increased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 7

Dependent Claim 52 words

The composition of claim 2, wherein at least one of said oligonucleotide analogue probes has decreased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 8

Dependent Claim 26 words

The composition of claims 1-5 or 6, wherein said solid substrate is selected from the group consisting of silica, polymeric materials, glass, beads, chips, and slides.

Claim 9

Dependent Claim 23 words

The composition of claims 1-5 or 6, wherein said composition comprises an array of oligonucleotide analogue probes 5 to 20 nucleotides in length.

Claim 10

Dependent Claim 118 words

The composition of claims 1-5 or 6, wherein said array of oligonucleotide analogue probes comprises a nucleoside analogue with the formula ##STR3## wherein: the nucleoside analogue is not a naturally occurring DNA or RNA nucleoside; R 1 is selected from the group consisting of hydrogen, methyl, hydroxyl, alkoxy, alkythio, halogen, cyano, and azido; R 2 is selected from the group consisting of hydrogen, methyl, hydroxyl, alkoxy, alkythio, halogen, cyano, and azido; Y is a heterocyclic moiety; and wherein said nucleoside analogue is incorporated into the oligonucleotide analogue by attachment to a 3' hydroxyl of the nucleoside analogue, to a 5' hydroxyl of the nucleoside analogue, or both the 3' nucleoside and the 5' hydroxyl of the nucleoside analogue.

Claim 11

Dependent Claim 139 words

The composition of claims 1-5 or 6, wherein said array of oligonucleotide analogue probes comprises a nucleoside analogue with the formula ##STR4## wherein: the nucleoside analogue is not a naturally occurring DNA or RNA nucleoside; R 1 is selected from the group consisting of hydrogen, hydroxyl, methyl, methoxy, ethoxy, propoxy, allyloxy, propargyloxy, Fluorine, Chlorine, and Bromine; R 2 is selected from the group consisting of hydrogen, hydroxyl, methyl, methoxy, ethoxy, propoxy, allyloxy, propargyloxy, Fluorine, Chlorine, and Bromine; and Y is a base selected from the group consisting of purines, purine analogues pyrimidines, pyrimidine analogues, 3-nitropyrrole and 5-nitroindole; and wherein said nucleoside analogue is incorporated into the oligonucleotide analogue by attachment to a 3' hydroxyl of the nucleoside analogue, to a 5' hydroxyl of the nucleoside analogue, or both the 3' nucleoside and the 5' hydroxyl of the nucleoside analogue.

Claim 12

Dependent Claim 37 words

The composition of claims 1-5 or 6, wherein each probe of said plurality of oligonucleotide analogue probes has at least one oligonucleotide analogue, and wherein at least one of said oligonucleotide analogues comprises a peptide nucleic acid.

Claim 13

Dependent Claim 29 words

The composition of claims 1-5 or 6, wherein at least one of said plurality of oligonucleotide analogue probes said array of oligonucleotide analogue probes is resistant to RNAase A.

Claim 14

Dependent Claim 20 words

The composition of claims 1-5 or 6, wherein said solid substrate is attached to over 1000 different oligonucleotide analogue probes.

Claim 15

Dependent Claim 35 words

The composition of claims 1-5 or 6, wherein each probe of said plurality of oligonucleotide analogue probes has at least one oligonucleotide analogue, and wherein at least one of said oligonucleotide analogues comprises 2'-O-methyl nucleotides.

Claim 16

Dependent Claim 82 words

The composition of claims 1-5 or 6, wherein said array of oligonucleotide analogue probes and said solid substrate comprises a plurality of different oligonucleotide analogue probes, each oligonucleotide analogue probes having the formula: Y--L.sup.1 --X.sup.1 --L.sup.2 --X.sup.2 wherein, Y is a solid substrate; X 1 and X 2 are complementary oligonucteotides containing at least one nucleotide analogue; L 1 is a spacer; L 2 is a linking group having sufficient length such that X 1 and X 2 form a double-stranded oligonucleotide.

Claim 17

Dependent Claim 17 words

The composition of claim 15, wherein said composition comprises a library of unimolecular double-stranded oligonucleotide analogue probes.

Claim 18

Dependent Claim 46 words

The composition of claims 1-5 or 6, wherein said array of oligonucleotide analogue probes comprises a conformationally restricted array of oligonucleotide analogue probes with the formula: --X.sup.11 --Z--X.sup.12 wherein X 11 and X 12 are complementary oligonucleotides or oligonucleotide analogues and Z is a presented moiety.

Claim 19

Dependent Claim 55 words

The composition of claims 1-5 or 6, wherein each probe of said plurality of oligonucleotide analogue probes has at least one oligonucleotide analogue, and wherein at least one of said oligonucleotide analogues comprises a nucleotide with a base selected from the group of bases consisting of 5-propynyluracil, 5-propynylcytosine, 2-aminoadenine, 7-deazaguanine, 2-aminopurine, 8-aza-7-deazaguanine, 1H-purine, and hypoxanthine.

Claim 20

Dependent Claim 24 words

The composition of claims 1-5 or 6, wherein said plurality of oligonucleotide analogue probes are coupled to said solid substrate by light-directed chemical coupling.

Claim 21

Dependent Claim 25 words

The composition of claim 19, wherein said solid substrate is derivitized with a silane reagent prior to synthesis of said plurality of oligonucleotide analogue probes.

Claim 22

Dependent Claim 32 words

The composition of claims 1-5 or 6, wherein said plurality of oligonucleotide analogue probes are coupled to said solid substrate by flowing oligonucleotide analogue reagents over known locations of the solid substrate.

Claim 23

Dependent Claim 25 words

The composition of claim 21, wherein said solid substrate is derivitized with a silane reagent prior to synthesis of said plurality of oligonucleotide analogue probes.

Claim 24

Dependent Claim 108 words

The composition of claims 1-5 or 6, wherein at least one of plurality of said oligonucleotide analogue probes forms a first duplex with a target oligonucleotide sequence, wherein said oligonucleotide analogue probe has a corresponding oligonucleotide sequence that forms a second duplex with said target oligonucleotide sequence, wherein said second duplex is rich in A-T or G-C nucleotide pairs, and wherein said oligonucleotide analogue probe has at least one nucleotide analogue in place of an A, T, G, or C nucleotide of said corresponding oligonucleotide sequence at a position within said oligonucleotide analogue probe such that said first duplex has an increased hybridization stability than said second duplex.

Claim 25

Dependent Claim 18 words

The composition of claim 23, wherein said oligonucleotide analogue probe contains fewer bases than said corresponding oligonucleotide sequence.

Claim 26

Dependent Claim 54 words

The composition of claims 1-5 or 6, wherein said oligonucleotide analogue probe forms a first duplex with a target oligonucleotide sequence, wherein said oligonucleotide analogue probe has a corresponding oligonucleotide sequence that forms a second duplex with said target polynucleotide sequence, and wherein said oligonucleotide analogue probe is shorter than said corresponding polynucleotide sequence.

Claim 27

Dependent Claim 50 words

A composition for analyzing the interaction between an oligonucleotide target and an oligonucleotide probe comprising an array of a plurality of oligonucleotide probes having different sequences hybridized to complementary oligonucleotide analogue targets, wherein said oligonucleotide analogue targets bind to complementary oligonucleotide probes with a similar hybridization stability across the array.

Claim 28

Dependent Claim 50 words

A composition for analyzing the interaction between an oligonucleotide target and an oligonucleotide probe comprising an array of a plurality of oligonucleotide probes having different sequences hybridized to complementary oligonucleotide analogue targets, wherein said oligonucleotide analogue targets bind to complementary oligonucleotide probes with a similar hybridization stability across the array.

Claim 29

Dependent Claim 28 words

The composition of claim 26, wherein at least one of said oligonucleotide analogue target is selected to maintain hybridization specificity or mismatch discrimination with said complementary oligonucleotide probes.

Claim 30

Dependent Claim 52 words

The composition of claim 26, wherein at least one of said oligonucleotide analogue targets has increased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 31

Dependent Claim 52 words

The composition of claim 26, wherein at least one of said oligonucleotide analogue targets has decreased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 32

Dependent Claim 52 words

The composition of claim 27, wherein at least one of said oligonucleotide analogue targets has increased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 33

Dependent Claim 52 words

The composition of claim 27, wherein at least one of said oligonucleotide analogue targets has decreased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 34

Dependent Claim 16 words

The composition of claims 26-30 or 31, wherein the oligonucleotide analogue target is a PCR amplicon.

Claim 35

Dependent Claim 23 words

The composition of claims 26-30 or 31, wherein at least one of said plurality of oligonucleotide probes comprise at least one oligonucleotide analogue.

Claim 36

Dependent Claim 20 words

The composition of claims 26-30 or 31, wherein at least one target oligonucleotide analogue acid is an RNA nucleic acid.

Claim 37

Independent Claim 113 words

A method analyzing interactions between an oligonucleotide target and an oligonucleotide probe, comprising the steps of: (a). synthesizing an oligonucleotide analogue array comprising a plurality of oligonucleotide analogue probes having different sequences, wherein said oligonucleotide analogue probes are coupled to a solid substrate at known locations, said solid substrate having a surface; (b). exposing said oligonucleotide analogue probe array to a plurality of oligonucleotide targets under hybridization conditions such that said plurality of oligonucleotide analogue probes bind to complementary oligonucleotide targets with a similar hybridization stability across the array; and (c). determining whether an oligonucleotide analogue probe of said oligonucleotide analogue probe array binds to at least one of said target nucleic acids.

Claim 38

Independent Claim 113 words

A method analyzing interactions between an oligonucleotide target and an oligonucleotide probe, comprising the steps of: (a). synthesizing an oligonucleotide analogue array comprising a plurality of oligonucleotide analogue probes having different sequences, wherein said oligonucleotide analogue probes are coupled to a solid substrate at known locations, said solid substrate having a surface; (b). exposing said oligonucleotide analogue probe array to a plurality of oligonucleotide targets under hybridization conditions such that said plurality of oligonucleotide analogue probes bind to complementary oligonucleotide targets with a similar hybridization stability across the array; and (c). determining whether an oligonucleotide analogue probe of said oligonucleotide analogue probe array binds to at least one of said target nucleic acids.

Claim 39

Dependent Claim 30 words

The method in accordance of claim 35, wherein at least one of said oligonucleotide analogue probes is selected to maintain hybridization specificity or mismatch discrimination with said complementary oligonucleotide targets.

Claim 40

Dependent Claim 54 words

The method in accordance of claim 35, wherein at least one of said oligonucleotide analogue probes has increased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 41

Dependent Claim 54 words

The method in accordance of claim 35, wherein at least one of said oligonucleotide analogue probes has decreased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 42

Dependent Claim 54 words

The method in accordance of claim 36, wherein at least one of said oligonucleotide analogue probes has increased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 43

Dependent Claim 54 words

The method in accordance of claim 36, wherein at least one of said oligonucleotide analogue probes has decreased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 44

Independent Claim 25 words

The method of claims 35-39 or 40, wherein said oligonucleotide target is selected from the group comprising genomic DNA, cDNA, unspliced RNA, mRNA, and rRNA.

Claim 45

Independent Claim 19 words

The method of claims 35-39 or 40, wherein said target nucleic acid is amplified prior to said hybridization step.

Claim 46

Independent Claim 23 words

The method of claims 35-39 or 40, wherein said plurality of oligonucleotide analogue probes is synthesized on said solid support by light-directed synthesis.

Claim 47

Independent Claim 36 words

The method of claims 35-39 or 40, wherein said plurality of said oligonucleotide analogue probes is synthesized on said solid support by causing oligonucleotide analogue synthetic reagents to flow over known locations of said solid support.

Claim 48

Independent Claim 67 words

The method of claims 35-39 or 40, wherein said step (a). comprises the steps of: i). forming a plurality of channels adjacent to the surface of said substrate; ii). placing selected reagents in said channels to synthesize oligonucleotide analogue probes at known locations; and iii). repeating steps i). and ii). thereby forming an array of oligonucleotide analogue probes having different sequences at known locations on said substrate.

Claim 49

Independent Claim 22 words

The method of claims 35-39 or 40, wherein said solid substrate is selected from the group consisting of beads, slides, and chips.

Claim 50

Independent Claim 25 words

The method of claims 35-39 or 40, wherein said solid substrate is comprised of materials selected from the group consisting of silica, polymers and glass.

Claim 51

Independent Claim 21 words

The method of claims 35-39 or 40, wherein the oligonucleotide analogue probes of said array are synthesized using photoremovable protecting groups.

Claim 52

Independent Claim 39 words

The method of claims 35-39 or 40, further comprising selectively incorporating MeNPoc onto the 3' or 5' hydroxyl of at least one nucleoside analogue and selectively incorporating said nucleoside analogue into at least one of said oligonucleotide analogue probes.

Claim 53

Independent Claim 22 words

The method of claims 35-39 or 40, wherein at least one of said oligonucleotide analogue probes is synthesized from phosphoramidite nucleoside reagents.

Claim 54

Independent Claim 88 words

A method of detecting an oligonucleotide target, comprising enzymatically copying an oligonucleotide target using at least one nucleotide analogue, thereby producing multiple oligonucleotide analogue targets, selecting said oligonucleotide analogue targets such that said oligonucleotide analogue targets bind to the complementary oligonucleotide probes coupled to a solid surface at known locations of an array with a similar hybridization stability across the array, hybridizing the oligonucleotide analogue targets to complementary oligonucleotide probes, and detecting whether at least one of said oligonuclotide analogue targets binds to said complementary oligonucleotide acid probe.

Claim 55

Independent Claim 88 words

A method of detecting an oligonucleotide target, comprising enzymatically copying an oligonucleotide target using at least one nucleotide analogue, thereby producing multiple oligonucleotide analogue targets, selecting said oligonucleotide analogue targets such that said oligonucleotide analogue targets bind to the complementary oligonucleotide probes coupled to a solid surface at known locations of an array with a similar hybridization stability across the array, hybridizing the oligonucleotide analogue targets to complementary oligonucleotide probes, and detecting whether at least one of said oligonuclotide analogue targets binds to said complementary oligonucleotide acid probe.

Claim 56

Dependent Claim 28 words

The method of claim 51, wherein at least one of said oligonucleotide analogue targets is selected to maintain hybridization specificity or mismatch discrimination with said complementary oligonucleotide probes.

Claim 57

Dependent Claim 52 words

The method of claim 51, wherein at least one of said oligonucleotide analogue targets has increased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 58

Dependent Claim 52 words

The method of claim 51, wherein at least one of said oligonucleotide analogue targets has decreased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 59

Dependent Claim 52 words

The method of claim 52, wherein at least one of said oligonucleotide analogue targets has increased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 60

Dependent Claim 52 words

The method of claim 52, wherein at least one of said oligonucleotide analogue targets has decreased the thermal stability between said oligonucleotide analogue target and said complementary oligonucleotide probe as compared to an oligonucleotide target that is the perfect complement to the complementary oligonucleotide probe with which said oligonucleotide analogue target anneals.

Claim 61

Independent Claim 31 words

The method of claims 51-55 or 56, wherein the oligonucleotide probe array comprises at least one oligonucleotide analogue probe which is complementary to at least one of said oligonucleotide analogue targets.

Claim 62

Independent Claim 70 words

A method of making an array of oligonucleotide probes, comprising providing a plurality of oligonucleotide analogue probes having at least one oligonucleotide analogue, said oligonucleotide analogue probes having different sequences at known locations on an array, selecting the oligonucleotide analogue probes to hybridize with complementary oligonucleotide target sequences under hybridization conditions such that said oligonucleotide analogue probes bind to complementary oligonucleotide targets with a similar hybridization stability, across the array.

Claim 63

Independent Claim 70 words

A method of making an array of oligonucleotide probes, comprising providing a plurality of oligonucleotide analogue probes having at least one oligonucleotide analogue, said oligonucleotide analogue probes having different sequences at known locations on an array, selecting the oligonucleotide analogue probes to hybridize with complementary oligonucleotide target sequences under hybridization conditions such that said oligonucleotide analogue probes bind to complementary oligonucleotide targets with a similar hybridization stability, across the array.

Claim 64

Dependent Claim 28 words

The method of claim 58, wherein at least one of said oligonucleotide analogue probes is selected to maintain hybridization specificity or mismatch discrimination with said complementary oligonucleotide targets.

Claim 65

Dependent Claim 52 words

The method of claim 58, wherein at least one of said oligonucleotide analogue probes has increased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 66

Dependent Claim 52 words

The method of claim 58, wherein at least one of said oligonucleotide analogue probes has decreased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 67

Dependent Claim 52 words

The method of claim 59, wherein at least one of said oligonucleotide analogue probes has increased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 68

Dependent Claim 52 words

The method of claim 59, wherein at least one of said oligonucleotide analogue probes has decreased the thermal stability between said oligonucleotide analogue probe and said complementary oligonucleotide target as compared to an oligonucleotide probe that is the perfect complement to the complementary oligonucleotide target with which said oligonucleotide analogue probe anneals.

Claim 69

Independent Claim 44 words

The method in accordance with claims 58-62, or 63, further comprising incorporating at least one oligonucleotide analogue into at least one of the oligonucleotide analogue probes of the array to reduce or prevent the formation of secondary structure in the oligonucleotide of the array.

Claim 70

Independent Claim 39 words

The method in accordance with claims 58-62, or 63, further comprising incorporating at least one oligonucleotide analogue into at least one of the oligonucleotide target to reduce or prevent the formation of secondary structure in the target polynucleotide sequence.

Claim 71

Independent Claim 39 words

The method in accordance with claims 58-62, or 63, further comprising incorporating at least one oligonucleotide analogue into at least one of the oligonucleotide analogue probes of the array to create secondary structure in the oligonucleotide of the array.

Claim 72

Independent Claim 37 words

The method in accordance with claims 58-62, or 63, further comprising incorporating a base selected from the group consisting of 5-propynyluracil, 5-propynylcytosine, 2-aminoadenine, 7-deazaguanine, 2-aminopurine, 8-aza-7-deazaguanine, 1H-purine, and hypoxanthine into the oligonucleotide analogue probes of the array.

Claim 73

Dependent Claim 23 words

The method of claim 67 further comprising selecting said at least one oligonucleotide analogue such that the oligonucleotide analogue probe is a homopolymer.

Claim 74

Independent Claim 50 words

The method in accordance with claims 58-62, or 63, further comprising selecting said at least one oligonucleotide analogue from the group consisting essentially of oligonucleotide analogues comprising 2'-O-methyl nucleotides and oligonucleotides comprising a base selected from the group of bases consisting of 5-propynyluracil, 5-propynylcytosine, 7-deazaguanine, 2-aminoadenine, 8-aza-7-deazaguanine, 1H-purine, and hypoxanthine.

Claim 75

Independent Claim 30 words

The method in accordance with claims 58-62 or 63, further comprising selecting said at least one oligonucleotide analogue such that oligonucleotide analogue probes comprises at least one peptide nucleic acid.

Claim 76

Independent Claim 48 words

The method in accordance with claims 58-62, or 63, further comprising selecting said at least one oligonucleotide analogue to increase image brightness when the oligonucleotide target and the oligonucleotide analogue probe hybridize in the presence of a fluorescent indicator, in comparison to a oligonucleotide probe without oligonucleotide analogs.

Claim 77

Independent Claim 29 words

The method in accordance with claims 58-62, or 63, further comprising providing said plurality of oligonucleotide analogue probes in an array with at least 1000 other oligonucleotide analogue probes.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2003-12-05	2004-06-05	2004-12-05	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2007-12-05	2008-06-05	2008-12-05	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2011-12-05	2012-06-05	2012-12-05	$7700.00	Window Closed / Lapsed

Arrays of modified nucleic acid probes and methods of use

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