US5801154A
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Antisense oligonucleotide modulation of multidrug resistance-associated protein
Assignee: Ionis Pharmaceuticals Inc
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Filing: 1997-04-08
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Granted: 1998-09-01
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Expires: 2017-04-08
Abstract
Abstract Compositions and methods are provided for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of the synthesis or metabolism of multidrug resistance-associated protein (MRP). In accordance with referred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding MRP. In a preferred embodiment, the oligonucleotide has at least one 2'-methoxyethoxy modification. Methods of preventing the development of multidrug resistance and of improving the efficacy of chemotherapy are also disclosed.
Inventors
- 👤 Edgardo Baracchini
- 👤 C. Frank Bennett
- 👤 Nicholas M. Dean
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 03:56
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/113; C12N15/1138; C07; C07H; C07H21/00; A; A61; A61K; A61K38/00; C12N2310/00; C12N2310/30; C12N2310/31; C12N2310/315; C12N2310/32; C12N2310/321; C12N2310/322; C12N2310/35; C12N2310/351; C12N2310/3517
Claims Analysis
Total Claims: 44
Claim 1
Independent Claim
27 words
An oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 2
Dependent Claim
27 words
An oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 3
Dependent Claim
15 words
The oligonucleotide of claim 1 which is specifically hybridizable with mRNA encoding multidrug resistance-associated protein.
Claim 4
Dependent Claim
20 words
The oligonucleotide of claim 1 which specifically hybridizes with DNA encoding multidrug resistance-associated protein to form a triple stranded structure.
Claim 5
Dependent Claim
34 words
The oligonucleotide of claim 2 specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequence, 3' untranslated sequence, coding sequence or an intron/exon junction of an mRNA encoding multidrug resistance-associated protein.
Claim 6
Dependent Claim
14 words
A pharmaceutical composition comprising an oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.
Claim 7
Dependent Claim
22 words
The oligonucleotide of claim 1 wherein at least one of the intersugar linkages between nucleotides of the oligonucleotide is a phosphorothioate linkage.
Claim 8
Dependent Claim
18 words
The oligonucleotide of claim 1 wherein at least one of the nucleotides is modified at the 2' position.
Claim 9
Dependent Claim
15 words
The oligonucleotide of claim 7 wherein the nucleotide modification is 2'-O-methyl, 2'-O-propyl, 2'-methoxyethoxy or 2'-fluoro.
Claim 10
Dependent Claim
10 words
The oligonucleotide of claim 8 which is a chimeric oligonucleotide.
Claim 11
Dependent Claim
10 words
The oligonucleotide of claim 9 which is a gapped oligonucleotide.
Claim 12
Dependent Claim
22 words
The oligonucleotide of claim 1 comprising SEQ ID NO: 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28.
Claim 13
Dependent Claim
36 words
An oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein, wherein said oligonucleotide comprises at least one 2'-methoxyethoxy modification.
Claim 14
Dependent Claim
36 words
An oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein, wherein said oligonucleotide comprises at least one 2'-methoxyethoxy modification.
Claim 15
Dependent Claim
10 words
The oligonucleotide of claim 12 which is a chimeric oligonucleotide.
Claim 16
Dependent Claim
10 words
The oligonucleotide of claim 13 which is a gapped oligonucleotide.
Claim 17
Dependent Claim
34 words
An oligonucleotide of claim 12 specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequence, 3' untranslated sequence, coding sequence or an intron/exon junction of an mRNA encoding multidrug resistance-associated protein.
Claim 18
Dependent Claim
14 words
A pharmaceutical composition comprising an oligonucleotide of claim 12 and a pharmaceutically acceptable carrier.
Claim 19
Dependent Claim
22 words
An oligonucleotide of claim 12 wherein at least one of the intersugar linkages between nucleotides of the oligonucleotide is a phosphorothioate linkage.
Claim 20
Dependent Claim
37 words
An oligonucleotide of claim 12 comprising SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28.
Claim 21
Dependent Claim
14 words
An oligonucleotide comprising SEQ ID NO: 8 and at least one 2' methoxyethoxy modification.
Claim 22
Dependent Claim
14 words
An oligonucleotide comprising SEQ ID NO: 8 and at least one 2' methoxyethoxy modification.
Claim 23
Dependent Claim
10 words
The oligonucleotide of claim 19 which is a chimeric oligonucleotide.
Claim 24
Dependent Claim
10 words
The oligonucleotide of claim 20 which is a gapped oligonucleotide.
Claim 25
Independent Claim
49 words
A method of inhibiting the synthesis of multidrug resistance-associated protein in a cell or tissue comprising contacting a cell or tissue with an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of modulating the expression of multidrug resistance-associated protein.
Claim 26
Independent Claim
49 words
A method of inhibiting the synthesis of multidrug resistance-associated protein in a cell or tissue comprising contacting a cell or tissue with an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of modulating the expression of multidrug resistance-associated protein.
Claim 27
Independent Claim
39 words
A method of inhibiting the synthesis of multidrug resistance-associated protein in a cell or tissue comprising contacting a cell or tissue with an oligonucleotide comprising an oligonucleotide comprising SEQ ID NO: 8 and at least one 2' methoxyethoxy modification.
Claim 28
Independent Claim
39 words
A method of inhibiting the synthesis of multidrug resistance-associated protein in a cell or tissue comprising contacting a cell or tissue with an oligonucleotide comprising an oligonucleotide comprising SEQ ID NO: 8 and at least one 2' methoxyethoxy modification.
Claim 29
Dependent Claim
12 words
The method of claim 23 wherein the oligonucleotide is a chimeric oligonucleotide.
Claim 30
Dependent Claim
12 words
The method of claim 23 wherein the oligonucleotide is a gapped oligonucleotide.
Claim 31
Independent Claim
57 words
A method of treating an animal suspected of having a condition which is characterized by overexpression of multidrug resistance-associated protein comprising administering to said animal a therapeutically effective amount of an oligonucleotide having 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 32
Independent Claim
57 words
A method of treating an animal suspected of having a condition which is characterized by overexpression of multidrug resistance-associated protein comprising administering to said animal a therapeutically effective amount of an oligonucleotide having 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 33
Dependent Claim
19 words
The method of claim 26 wherein the oligonucleotide is administered in conjunction with a chemotherapeutic drug treatment for cancer.
Claim 34
Dependent Claim
12 words
The method of claim 27 wherein the condition is a multidrug-resistant cancer.
Claim 35
Dependent Claim
13 words
The method of claim 27 wherein the multidrug-resistant cancer is small-cell lung cancer.
Claim 36
Independent Claim
52 words
A method for improving the efficacy of a chemotherapeutic drug treatment of a disease, said method comprising administering in conjunction with a chemotherapeutic drug treatment an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 37
Independent Claim
52 words
A method for improving the efficacy of a chemotherapeutic drug treatment of a disease, said method comprising administering in conjunction with a chemotherapeutic drug treatment an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 38
Dependent Claim
10 words
The method of claim 30 wherein the disease is cancer.
Claim 39
Independent Claim
55 words
A method for preventing the development of multidrug resistance during a chemotherapeutic drug treatment of a disease, said method comprising administering in conjunction with a chemotherapeutic drug treatment an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 40
Independent Claim
55 words
A method for preventing the development of multidrug resistance during a chemotherapeutic drug treatment of a disease, said method comprising administering in conjunction with a chemotherapeutic drug treatment an oligonucleotide comprising 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 41
Dependent Claim
10 words
The method of claim 32 wherein the disease is cancer.
Claim 42
Independent Claim
54 words
A method of treating an animal suspected of having a condition which is characterized by leukotriene production comprising administering to said animal a therapeutically effective amount of an oligonucleotide having 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 43
Independent Claim
54 words
A method of treating an animal suspected of having a condition which is characterized by leukotriene production comprising administering to said animal a therapeutically effective amount of an oligonucleotide having 8 to 30 nucleotides specifically hybridizable with a nucleic acid encoding multidrug resistance-associated protein and capable of inhibiting the expression of multidrug resistance-associated protein.
Claim 44
Dependent Claim
12 words
The method of claim 34 wherein the condition is an inflammatory condition.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-08-31 | 2002-03-02 | 2002-09-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-08-31 | 2006-03-02 | 2006-09-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-08-31 | 2010-03-02 | 2010-09-01 | $7700.00 | Window Closed / Lapsed |