Patent US6297014B1 successfully refreshed from Google Patents.
US6297014B1
Expired / Lapsed
US
⏱️ 0.0 years remaining
Genetic test to determine non-responsiveness to statin drug treatment
Assignee: Cedars-Sinai Medical Center
•
Filing: 1999-07-02
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Granted: 2001-10-02
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Expires: 2019-07-02
Abstract
Abstract In a method for detecting a genetic predisposition in a human for non-responsiveness to statin drug treatment for coronary artery disease, nucleic acids comprising nucleotide sequences of the human lipoprotein lipase (LPL) gene are amplified and analyzed. Homozygosity for a variant allele in a non-coding or untranslated region of the 3' end of LPL, for example, LPL HindIII 2/2 or (TTTA)n 4/4 genotypes, is linked to non-responsiveness to treatment with statin drugs, including lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, or cerivastatin. Oligonucleotide primer sequences, primer sets, and genetic testing kits allow the practitioner to practice the method and thus better individualize the treatment and improve the care of patients with coronary artery disease.
Inventors
- 👤 Kent D. Taylor
- 👤 Maren T. Scheuner
- 👤 Jerome I. Rotter
- 👤 Huiying Yang
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:41
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6876; C12Q1/6883; C12Q2600/00; C12Q2600/156
Claims Analysis
Total Claims: 61
Claim 1
Independent Claim
125 words
A method of detecting a genetic predisposition in a human subject for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin, comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids that include the normal locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene (LPL) from said tissue sample to obtain amplification products; and c) analyzing the amplification products for the absence of a HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin.
Claim 2
Independent Claim
125 words
A method of detecting a genetic predisposition in a human subject for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin, comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids that include the normal locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene (LPL) from said tissue sample to obtain amplification products; and c) analyzing the amplification products for the absence of a HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin.
Claim 3
Dependent Claim
14 words
The method of claim 1 , wherein the tissue sample is a blood sample.
Claim 4
Dependent Claim
21 words
The method of claim 1 , further comprising restricting the amplification products with a restriction enzyme before analyzing the amplification products.
Claim 5
Dependent Claim
12 words
The method of claim 1 , wherein the restriction enzyme is HindIII.
Claim 6
Dependent Claim
17 words
The method of claim 1 , wherein an oligonucleotide primer is used in amplifying said nucleic acids.
Claim 7
Dependent Claim
32 words
The method of claim 1 , wherein an oligonucleotide primer comprising the sequence GCA TCT GCC TTC AGC TAG ACA TTG (SEQ. ID. NO. 1) is used in amplifying said nucleic acids.
Claim 8
Dependent Claim
32 words
The method of claim 1 , wherein an oligonucleotide primer comprising the sequence TCT TCC AGA AGG GTG AGA TTC CAA (SEQ. ID. NO. 2) is used in amplifying said nucleic acids.
Claim 9
Dependent Claim
45 words
The method of claim 1 , wherein an oligonucleotide primer having the sequence GCA TCT GCC TTC AGC TAG ACA TTG (SEQ. ID. NO. 1) or TCT TCC AGA AGG GTG AGA TTC CAA (SEQ. ID. NO. 2) is used in amplifying said nucleic acids.
Claim 10
Dependent Claim
53 words
The method of claim 1 , wherein a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2) are used in amplifying said nucleic acids.
Claim 11
Dependent Claim
284 words
The method of claim 1 , wherein an oligonucleotide primer is used in amplifying said nucleic acids, said primer comprising a sequence selected from the group essentially consisting of (SEQ. ID. NO.:1), (SEQ. ID. NO.:2), (SEQ. ID. NO.:3), (SEQ. ID. NO.:4), (SEQ. ID. NO.:5), (SEQ. ID. NO.:6), (SEQ. ID. NO.:7), (SEQ. ID. NO.:8), (SEQ. ID. NO.:9), (SEQ. ID. NO.:10), (SEQ. ID. NO.:10), (SEQ. ID. NO.:11), (SEQ. ID. NO.:12), (SEQ. ID. NO.:13), (SEQ. ID. NO.:14), (SEQ. ID. NO.:15), (SEQ. ID. NO.:16), (SEQ. ID. NO.:17), (SEQ. ID. NO.:18), (SEQ. ID. NO.:19), (SEQ. ID. NO.:20), (SEQ. ID. NO.:21), (SEQ. ID. NO.:22), (SEQ. ID. NO.:23), (SEQ. ID. NO.:24), (SEQ. ID. NO.:25), (SEQ. ID. NO.:26), (SEQ. ID. NO.:27), (SEQ. ID. NO.:28), (SEQ. ID. NO.:29), (SEQ. ID. NO.:30), (SEQ. ID. NO.:31), (SEQ. ID. NO.:32), (SEQ. ID. NO.:35), (SEQ. ID. NO.:36), (SEQ. ID. NO.:37), (SEQ. ID. NO.:38), (SEQ. ID. NO.:39), (SEQ. ID. NO.:40), (SEQ. ID. NO.:41), (SEQ. ID. NO.:42), (SEQ. ID. NO.:43), (SEQ. ID. NO.:44), (SEQ. ID. NO.:45),(SEQ. ID. NO.:46), (SEQ. ID. NO.:47), (SEQ. ID. NO.:48), (SEQ. ID. NO.:49), (SEQ. ID. NO.:50), (SEQ. ID. NO.:51), (SEQ. ID. NO.:52), (SEQ. ID. NO.:53), (SEQ. ID. NO.:54), (SEQ. ID. NO.:55), (SEQ. ID. NO.:56), (SEQ. ID. NO.:57), (SEQ. ID. NO.:58), (SEQ. ID. NO.:59), (SEQ. ID. NO.:60), (SEQ. ID. NO.:61), (SEQ. ID. NO.:62), (SEQ. ID. NO.:63), (SEQ. ID. NO.:64), (SEQ. ID. NO.:65), (SEQ. ID. NO.:66), (SEQ. ID. NO.:67), (SEQ. ID. NO.:68), (SEQ. ID. NO.:69), (SEQ. ID. NO.:70), (SEQ. ID. NO.:71), (SEQ. ID. NO.:72), (SEQ. ID. NO.:73), (SEQ. ID. NO.:74), (SEQ. ID. NO.:75), (SEQ. ID. NO.:76), (SEQ. ID. NO.:77), (SEQ. ID. NO.:78), or (SEQ. ID. NO.:79), or comprising a sequence overlapping the sequence of any of these with respect to its position on the Nickerson reference sequence.
Claim 12
Dependent Claim
16 words
The method of claim 5 , wherein said oligonucleotide primer is labeled with a fluorescent dye.
Claim 13
Dependent Claim
24 words
The method of claim 11 , wherein said dye is SYBR Green I, YO-PRO-1, thiazole orange, Hex, pico green, edans, fluorescein, FAM, or TET.
Claim 14
Independent Claim
112 words
A method of detecting a genetic predisposition for non-responsiveness to lovastatin, pravastatin, or simvastatin treatment in a human subject with coronary artery disease, comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids comprising the HindIII restriction site in intron 8 of the human lipoprotein lipase gene (LPL) from said tissue sample to obtain amplification products; and c) analyzing the amplification products for the absence of a HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition in said human subject for non-responsiveness to lovastatin, pravastatin, or simvastatin treatment for coronary artery disease.
Claim 15
Independent Claim
112 words
A method of detecting a genetic predisposition for non-responsiveness to lovastatin, pravastatin, or simvastatin treatment in a human subject with coronary artery disease, comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids comprising the HindIII restriction site in intron 8 of the human lipoprotein lipase gene (LPL) from said tissue sample to obtain amplification products; and c) analyzing the amplification products for the absence of a HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition in said human subject for non-responsiveness to lovastatin, pravastatin, or simvastatin treatment for coronary artery disease.
Claim 16
Dependent Claim
14 words
The method of claim 13 , wherein the tissue sample is a blood sample.
Claim 17
Dependent Claim
21 words
The method of claim 13 , further comprising restricting the amplification products with a restriction enzyme before analyzing the amplification products.
Claim 18
Dependent Claim
12 words
The method of claim 13 , wherein the restriction enzyme is HindIII.
Claim 19
Dependent Claim
17 words
The method of claim 13 , wherein an oligonucleotide primer is used in amplifying said nucleic acids.
Claim 20
Dependent Claim
28 words
The method of claim 13 , comprising the sequence GCA TCT GCC TTC AGC TAG ACA TTG (SEQ. ID. NO. 1) is used in amplifying said nucleic acids.
Claim 21
Dependent Claim
32 words
The method of claim 13 , wherein an oligonucleotide primer comprising the sequence TCT TCC AGA AGG GTG AGA TTC CAA (SEQ. ID. NO. 2) is used in amplifying said nucleic acids.
Claim 22
Dependent Claim
45 words
The method of claim 13 , wherein an oligonucleotide primer having the sequence GCA TCT GCC TTC AGC TAG ACA TTG (SEQ. ID. NO. 1) or TCT TCC AGA AGG GTG AGA TTC CAA (SEQ. ID. NO. 2) is used in amplifying said nucleic acids.
Claim 23
Dependent Claim
53 words
The method of claim 13 , wherein a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2) are used in amplifying said nucleic acids.
Claim 24
Dependent Claim
276 words
The method of claim 13 , wherein an oligonucleotide primer is used in amplifying said nucleic acids, said primer comprising a nucleotide sequence of (SEQ. ID. NO.:1), (SEQ. ID. NO.:2), (SEQ. ID. NO.:3), (SEQ. ID. NO.:4), (SEQ. ID. NO.:5), (SEQ. ID. NO.:6), (SEQ. ID. NO.:7), (SEQ. ID. NO.:8), (SEQ. ID. NO.:9), (SEQ. ID. NO.:10), (SEQ. ID. NO.:11), (SEQ. ID. NO.:12), (SEQ. ID. NO.:13), (SEQ. ID. NO.:14), (SEQ. ID. NO.:15), (SEQ. ID. NO.:16), (SEQ. ID. NO.:17), (SEQ. ID. NO.:18), (SEQ. ID. NO.:19), (SEQ. ID. NO.:20), (SEQ. ID. NO.:21), (SEQ. ID. NO.22), (SEQ. ID. NO.:23), (SEQ. ID. NO.:24), (SEQ. ID. NO.:25), (SEQ. ID. NO.:26), (SEQ. ID. NO.27), (SEQ. ID. NO.:28), (SEQ. ID. NO.:29), (SEQ. ID. NO.:30), (SEQ. ID. NO.:31), (SEQ. ID. NO.:32), (SEQ. ID. NO.:35), (SEQ. ID. NO.:36), (SEQ. ID. NO.:37), (SEQ. ID. NO.:38), (SEQ. ID. NO.:39), (SEQ. ID. NO.:40), (SEQ. ID. NO.:41), (SEQ. ID. NO.:42), (SEQ. ID. NO.:43), (SEQ. ID. NO.:44), (SEQ. ID. NO.:45),(SEQ. ID. NO.:46), (SEQ. ID. NO.:47), (SEQ. ID. NO.:48), (SEQ. ID. NO.:49), (SEQ. ID. NO.:50), (SEQ. ID. NO.:51), (SEQ. ID. NO.:52), (SEQ. ID. NO.:53), (SEQ. ID. NO.:54), (SEQ. ID. NO.:55), (SEQ. ID. NO.:56), (SEQ. ID. NO.:57), (SEQ. ID. NO.:58), (SEQ. ID. NO.:59), (SEQ. ID. NO.:60), (SEQ. ID. NO.:61), (SEQ. ID. NO.:62), (SEQ. ID. NO.:63), (SEQ. ID. NO.:64), (SEQ. ID. NO.:65), (SEQ. ID. NO.:66), (SEQ. ID. NO.:67), (SEQ. ID. NO.:68), (SEQ. ID. NO.:69), (SEQ. ID. NO.:70), (SEQ. ID. NO.:71), (SEQ. ID. NO.:72), (SEQ. ID. NO.:73), (SEQ. ID. NO.:74), (SEQ. ID. NO.:75), (SEQ. ID. NO.:76), (SEQ. ID. NO.:77), (SEQ. ID. NO.:78), or (SEQ. ID. NO.:79), or comprising a sequence overlapping the sequence of any of these with respect to its position on the Nickerson reference sequence.
Claim 25
Dependent Claim
16 words
The method of claim 13 , wherein said oligonucleotide primer is labeled with a fluorescent dye.
Claim 26
Dependent Claim
24 words
The method of claim 23 , wherein said dye is SYBR Green I, YO-PRO-1, thiazole orange, Hex, pico green, edans, fluorescein, FAM, or TET.
Claim 27
Dependent Claim
17 words
The method of claim 13 , wherein said human subject is a coronary artery bypass graft patient.
Claim 28
Independent Claim
130 words
A method of detecting genetic predisposition in a CABG patient for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin, comprising: a) collecting a tissue sample from a CABG patient; b) amplifying nucleic acids comprising the locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase (LPL) gene from said blood sample to obtain amplification products; and c) analyzing the amplification products for the absence of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition in said CABG patient for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin.
Claim 29
Independent Claim
130 words
A method of detecting genetic predisposition in a CABG patient for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin, comprising: a) collecting a tissue sample from a CABG patient; b) amplifying nucleic acids comprising the locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase (LPL) gene from said blood sample to obtain amplification products; and c) analyzing the amplification products for the absence of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition in said CABG patient for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, and simvastatin.
Claim 30
Dependent Claim
14 words
The method of claim 26 , wherein said tissue sample is a blood sample.
Claim 31
Dependent Claim
21 words
The method of claim 26 , further comprising restricting the amplification products with a restriction enzyme before analyzing the amplification products.
Claim 32
Dependent Claim
12 words
The method of claim 28 , wherein the restriction enzyme is HindIII.
Claim 33
Dependent Claim
17 words
The method of claim 26 , wherein an oligonucleotide primer is used in amplifying said nucleic acids.
Claim 34
Dependent Claim
28 words
The method of claim 26 , comprising the sequence GCA TCT GCC TTC AGC TAG ACA TTG (SEQ. ID. NO. 1) is used in amplifying said nucleic acids.
Claim 35
Dependent Claim
32 words
The method of claim 26 , wherein an oligonucleotide primer comprising the sequence TCT TCC AGA AGG GTG AGA TTC CAA (SEQ. ID. NO. 2) is used in amplifying said nucleic acids.
Claim 36
Dependent Claim
45 words
The method of claim 26 , wherein an oligonucleotide primer having the sequence GCA TCT GCC TTC AGC TAG ACA TTG (SEQ. ID. NO. 1) or TCT TCC AGA AGG GTG AGA TTC CAA (SEQ. ID. NO. 2) is used in amplifying said nucleic acids.
Claim 37
Dependent Claim
53 words
The method of claim 26 , wherein a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2) are used in amplifying said nucleic acids.
Claim 38
Dependent Claim
275 words
The method of claim 26 , wherein an oligonucleotide primer is used in amplifying said nucleic acids, said primer comprising a sequence of (SEQ. ID. NO.:1), (SEQ. ID. NO.:2), (SEQ. ID. NO.:3), (SEQ. ID. NO.:4), (SEQ. ID. NO.:5), (SEQ. ID. NO.:6), (SEQ. ID. NO.:7), (SEQ. ID. NO.:8), (SEQ. ID. NO.:9), (SEQ. ID. NO.:10), (SEQ. ID. NO.:11), (SEQ. ID. NO.:12), (SEQ. ID. NO.:13), (SEQ. ID. NO.:14), (SEQ. ID. NO.:15), (SEQ. ID. NO.:16), (SEQ. ID. NO.:17), (SEQ. ID. NO.:18), (SEQ. ID. NO.:19), (SEQ. ID. NO.:20), (SEQ. ID. NO.:21), (SEQ. ID. NO.:22), (SEQ. ID. NO.:23), (SEQ. ID. NO.:24), (SEQ. ID. NO.:25), (SEQ. ID. NO.:26), (SEQ. ID. NO.:27), (SEQ. ID. NO.:28), (SEQ. ID. NO.:29), (SEQ. ID. NO.:30), (SEQ. ID. NO.:31), (SEQ. ID. NO.:32), (SEQ. ID. NO.:35), (SEQ. ID. NO.:36), (SEQ. ID. NO.:37), (SEQ. ID. NO.:38), (SEQ. ID. NO.:39), (SEQ. ID. NO.:40), (SEQ. ID. NO.:41), (SEQ. ID. NO.:42), (SEQ. ID. NO.:43), (SEQ. ID. NO.:44), (SEQ. ID. NO.:45),(SEQ. ID. NO.:46), (SEQ. ID. NO.:47), (SEQ. ID. NO.:48), (SEQ. ID. NO.:49), (SEQ. ID. NO.:50), (SEQ. ID. NO.:51), (SEQ. ID. NO.:52), (SEQ. ID. NO.:53), (SEQ. ID. NO.:54), (SEQ. ID. NO.:55), (SEQ. ID. NO.:56), (SEQ. ID. NO.:57), (SEQ. ID. NO.:58), (SEQ. ID. NO.:59), (SEQ. ID. NO.:60), (SEQ. ID. NO.:61), (SEQ. ID. NO.:62), (SEQ. ID. NO.:63), (SEQ. ID. NO.:64), (SEQ. ID. NO.:65), (SEQ. ID. NO.:66), (SEQ. ID. NO.:67), (SEQ. ID. NO.:68), (SEQ. ID. NO.:69), (SEQ. ID. NO.:70), (SEQ. ID. NO.:71), (SEQ. ID. NO.:72), (SEQ. ID. NO.:73), (SEQ. ID. NO.:74), (SEQ. ID. NO.:75), (SEQ. ID. NO.:76), (SEQ. ID. NO.:77), (SEQ. ID. NO.:78), or (SEQ. ID. NO.:79), or comprising a sequence overlapping the sequence of any of these with respect to its position on the Nickerson reference sequence.
Claim 39
Dependent Claim
16 words
The method of claim 30 , wherein said oligonucleotide primer is labeled with a fluorescent dye.
Claim 40
Dependent Claim
24 words
The method of claim 36 , wherein said dye is SYBR Green I, YO-PRO-1, thiazole orange, Hex, pico green, edans, fluorescein, FAM, or TET.
Claim 41
Independent Claim
153 words
A method of detecting genetic predisposition in a CABG for non-responsiveness to treatment with lovastatin, pravastatin, or simvastatin, comprising: a) collecting a tissue sample from a CABG patient, b) amplifying nucleic acids comprising the normal locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase (LPL) gene from said blood sample to obtain amplification products, by using a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2); and c) analyzing the amplification products for the absence of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition in said CABG patient for non-responsiveness to treatment for coronary artery disease with lovastatin, pravastatin, or simvastatin.
Claim 42
Independent Claim
153 words
A method of detecting genetic predisposition in a CABG for non-responsiveness to treatment with lovastatin, pravastatin, or simvastatin, comprising: a) collecting a tissue sample from a CABG patient, b) amplifying nucleic acids comprising the normal locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase (LPL) gene from said blood sample to obtain amplification products, by using a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2); and c) analyzing the amplification products for the absence of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene, homozygosity for an absence of said HindIII recognition site indicating a genetic predisposition in said CABG patient for non-responsiveness to treatment for coronary artery disease with lovastatin, pravastatin, or simvastatin.
Claim 43
Dependent Claim
14 words
The method of claim 38 , wherein said tissue sample is a blood sample.
Claim 44
Dependent Claim
16 words
The method of claim 38 , wherein said oligonucleotide primer is labeled with a fluorescent dye.
Claim 45
Dependent Claim
24 words
The method of claim 40 , wherein said dye is SYBR Green I, YO-PRO-1, thiazole orange, Hex, pico green, edans, fluorescein, FAM, or TET.
Claim 46
Independent Claim
183 words
A method of detecting in a human subject a genetic predisposition for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin, said method comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids comprising the normal locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase (LPL) gene from said blood sample to obtain amplification products, by using a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2); c) restricting said amplification products with HindIII; and d) analyzing the restriction fragments for the absence of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene, wherein homozygosity for an absence of said HindIII recognition site indicates a genetic predisposition for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin.
Claim 47
Independent Claim
183 words
A method of detecting in a human subject a genetic predisposition for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin, said method comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids comprising the normal locus of the HindIII recognition site in intron 8 of the human lipoprotein lipase (LPL) gene from said blood sample to obtain amplification products, by using a reverse oligonucleotide primer having the sequence 5′-GCA TCT GCC TTC AGC TAG ACA TTG-3′ (SEQ. ID. NO. 1) and a forward oligonucleotide primer having the sequence 5′-TCT TCC AGA AGG GTG AGA TTC CAA-3′ (SEQ. ID. NO. 2); c) restricting said amplification products with HindIII; and d) analyzing the restriction fragments for the absence of the HindIII recognition site in intron 8 of the human lipoprotein lipase gene, wherein homozygosity for an absence of said HindIII recognition site indicates a genetic predisposition for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin.
Claim 48
Dependent Claim
14 words
The method of claim 42 , wherein the tissue sample is a blood sample.
Claim 49
Dependent Claim
16 words
The method of claim 42 , wherein said oligonucleotide primer is labeled with a fluorescent dye.
Claim 50
Dependent Claim
24 words
The method of claim 42 , wherein said dye is SYBR Green I, YO-PRO-1, thiazole orange, Hex, pico green, edans, fluorescein, FAM, or TET.
Claim 51
Independent Claim
124 words
A method of detecting a genetic predisposition in a human subject for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin, said method comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids comprising the normal locus of the (TTTA) n tetranucleotide repeat sequence in intron 6 of the human lipoprotein lipase gene (LPL) from said tissue sample to obtain amplification products; and c) analyzing the amplification products for (TTTA) n tetranucleotide repeat alleles present in said nucleic acids, homozygosity for a (TTTA) n 4 allele indicating a genetic predisposition for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin.
Claim 52
Independent Claim
124 words
A method of detecting a genetic predisposition in a human subject for non-responsiveness to treatment with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin, said method comprising: a) collecting a tissue sample from a human subject; b) amplifying nucleic acids comprising the normal locus of the (TTTA) n tetranucleotide repeat sequence in intron 6 of the human lipoprotein lipase gene (LPL) from said tissue sample to obtain amplification products; and c) analyzing the amplification products for (TTTA) n tetranucleotide repeat alleles present in said nucleic acids, homozygosity for a (TTTA) n 4 allele indicating a genetic predisposition for non-responsiveness to treatment for coronary artery disease with a statin drug selected from the group consisting of lovastatin, pravastatin, or simvastatin.
Claim 53
Dependent Claim
14 words
The method of claim 46 , wherein the tissue sample is a blood sample.
Claim 54
Dependent Claim
17 words
The method of claim 46 , wherein an oligonucleotide primer is used in amplifying said nucleic acids.
Claim 55
Dependent Claim
28 words
The method of claim 46 , comprising the sequence 5′-CCT GGG TAA CTG AGC GAG ACT GTG TC-3′ (SEQ. ID. NO.:33) is used in amplifying said nucleic acids.
Claim 56
Dependent Claim
33 words
The method of claim 46 , wherein an oligonucleotide primer comprising the sequence 5′- ATC TGA CCA AGG ATA GTG GGA TAT A-3′ (SEQ. ID. NO.:34) is used in amplifying said nucleic acids.
Claim 57
Dependent Claim
45 words
The method of claim 46 , wherein an oligonucleotide primer having the sequence 5′-CCT GGG TAA CTG AGC GAG ACT GTG TC-3′ (SEQ. ID. NO.:33) or 5′-ATC TGA CCA AGG ATA GTG GGA TAT A-3′ (SEQ. ID. NO.:34) is used in amplifying said nucleic acids.
Claim 58
Dependent Claim
53 words
The method of claim 46 , wherein a reverse oligonucleotide primer having the sequence 5′-CCT GGG TAA CTG AGC GAG ACT GTG TC-3′ (SEQ. ID. NO.:33) and a forward oligonucleotide primer having the sequence 5′-ATC TGA CCA AGG ATA GTG GGA TAT A-3′ (SEQ. ID. NO.:34) are used in amplifying said nucleic acids.
Claim 59
Dependent Claim
83 words
The method of claim 46 , wherein amplifying said nucleic acids is done using an oligonucleotide primer comprising a nucleotide sequence of (SEQ. ID. NO.:33), (SEQ. ID. NO.:34), (SEQ. ID. NO.:82), (SEQ. ID. NO.:83), (SEQ. ID. NO.:84), (SEQ. ID. NO.:85), (SEQ. ID. NO.:86), (SEQ. ID. NO.:87), (SEQ. ID. NO.:88), (SEQ. ID. NO.:89), (SEQ. ID. NO.:90), (SEQ. ID. NO.:91), or (SEQ. ID. NO.:92), or comprising a sequence overlapping the sequence of any of these with respect to its position on the Nickerson reference sequence.
Claim 60
Dependent Claim
16 words
The method of claim 53 , wherein said oligonucleotide primer is labeled with a fluorescent dye.
Claim 61
Dependent Claim
24 words
The method of claim 54 , wherein said dye is SYBR Green I, YO-PRO-1, thiazole orange, Hex, pico green, edans, fluorescein, FAM, or TET.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2004-10-01 | 2005-04-02 | 2005-10-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-10-01 | 2009-04-02 | 2009-10-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-10-01 | 2013-04-02 | 2013-10-02 | $7700.00 | Window Closed / Lapsed |