CA2266584A1 - Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides - Google Patents

Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides

Info

Publication number
CA2266584A1
CA2266584A1 CA002266584A CA2266584A CA2266584A1 CA 2266584 A1 CA2266584 A1 CA 2266584A1 CA 002266584 A CA002266584 A CA 002266584A CA 2266584 A CA2266584 A CA 2266584A CA 2266584 A1 CA2266584 A1 CA 2266584A1
Authority
CA
Canada
Prior art keywords
polynucleotide
composition
lipid
bcl
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002266584A
Other languages
French (fr)
Other versions
CA2266584C (en
Inventor
Mar Tormo
Ana M. Tari
Gabriel Lopez-Berestein
Timothy J. Mcdonnell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
Original Assignee
Board Of Regents, The University Of Texas System
Mar Tormo
Ana M. Tari
Gabriel Lopez-Berestein
Timothy J. Mcdonnell
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Board Of Regents, The University Of Texas System, Mar Tormo, Ana M. Tari, Gabriel Lopez-Berestein, Timothy J. Mcdonnell filed Critical Board Of Regents, The University Of Texas System
Priority to CA2677176A priority Critical patent/CA2677176C/en
Publication of CA2266584A1 publication Critical patent/CA2266584A1/en
Application granted granted Critical
Publication of CA2266584C publication Critical patent/CA2266584C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/312—Phosphonates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification

Abstract

The present invention provides novel compositions and methods for use in the treatment of Bcl-2-associated diseases like cancer, specifically, in the treatment of follicular lymphoma (FL). The compositions contain antisense oligonucleotides that hybridize to Bcl-2 nucleic acids, the gene products of which are known to interact with the tumorigenic protein Bcl-2. Used alone, or in conjunction with other antisense oligonucleotides, these compositions inhibit the proliferation of FL cancer cells.

Claims (20)

1. A composition comprising a first polynucleotide that hybridizes to a second, Bc1-2-encoding polynucleotide under intracellular conditions and a neutral lipid associated with said first polynucleotide, and wherein said composition contains no cationic lipid.
2. The composition of claim 1, wherein said first polynucleotide is an oligonucleotide having a length of between about 8 and about 50 bases.
3. The composition of claim 1, wherein the first polynucleotide is complementary to the translation initiation site of Bc1-2 mRNA.
4. The composition of claim 3, wherein the polynucleotide is an oligonucleotide comprising the sequence CAGCGTGCGCCATCCTTC (SEQ ID NO:1).
5. The composition of claim 1, comprising a liposome formed from the lipid.
6. The composition of claim 5, wherein the first polynucleotide is encapsulated in the liposome.
7. The composition of claim 1, wherein the lipid is a phosphatidylcholine, a phosphatidylglycerol, or a phosphatidylethanolamine.
8. The composition of claim 7, wherein the lipid is dioleoylphosphatidylcholine.
9. A composition comprising an expression construct that encodes a first polynucleotide that hybridizes to a second, polynucleotide under intracellular conditions, wherein said first polynucleotide is under the control of a promoter that is active in eukaryotic cells, and wherein said construct is associated with a neutral lipid, and further wherein said composition contains no cationic lipid.
10. A method of inhibiting a Bcl-2-associated disease comprising obtaining a first polynucleotide that hybridizes to a second, Bcl-2-encoding polynucleotide under intracellular conditions, mixing the first polynucleotide with a neutral lipid to form a polynucleotide/lipid association, and administering said association to a cell, wherein said cell expresses both Bc1-2 and Bax.
11. The method of claim 10, wherein the cell is a cancer cell.
12. The method of claim 11, wherein said cancer cell is a follicular lymphoma cell.
13. The method of claim 10, wherein said first polynucleotide is an oligonucleotide having a length of between about 8 and about 50 bases.
14. The method of claim 10, comprising a liposome formed from the lipid.
IS. The method of claim 14, wherein the liposome encapsulates the first polynucleotide.
16. The method of claim 10, wherein said contacting takes place in an animal.
17. The method of claim 16, wherein said animal is a human.
18. The method of claim 17, wherein said composition is delivered to said human in a volume of 0.50-10.0 ml per dose.
19. The method of claim 17, wherein said composition is delivered to said human in an amount of from about 5 to about 30 mg polynucleotide per m 2.
20. The method of claim 19, wherein said composition is administered three times per week for eight weeks.
CA002266584A 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides Expired - Fee Related CA2266584C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2677176A CA2677176C (en) 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/726,211 US6977244B2 (en) 1996-10-04 1996-10-04 Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides
US08/726,211 1996-10-04
PCT/US1997/018348 WO1998014172A1 (en) 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2677176A Division CA2677176C (en) 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides

Publications (2)

Publication Number Publication Date
CA2266584A1 true CA2266584A1 (en) 1998-04-09
CA2266584C CA2266584C (en) 2009-12-08

Family

ID=24917657

Family Applications (2)

Application Number Title Priority Date Filing Date
CA002266584A Expired - Fee Related CA2266584C (en) 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides
CA2677176A Expired - Fee Related CA2677176C (en) 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA2677176A Expired - Fee Related CA2677176C (en) 1996-10-04 1997-10-03 Inhibition of bcl-2 protein expression by liposomal antisense oligodeoxynucleotides

Country Status (8)

Country Link
US (2) US6977244B2 (en)
EP (1) EP0939621B1 (en)
JP (2) JP4402746B2 (en)
AT (1) ATE334657T1 (en)
CA (2) CA2266584C (en)
DE (1) DE69736432T2 (en)
ES (1) ES2270454T3 (en)
WO (1) WO1998014172A1 (en)

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US6977244B2 (en) 2005-12-20
US20030012812A1 (en) 2003-01-16
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DE69736432D1 (en) 2006-09-14
WO1998014172A1 (en) 1998-04-09
JP2001502172A (en) 2001-02-20
JP4402746B2 (en) 2010-01-20
EP0939621B1 (en) 2006-08-02
EP0939621A1 (en) 1999-09-08
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CA2677176A1 (en) 1998-04-09
CA2266584C (en) 2009-12-08

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