CA2228944A1 - Liposomal phosphodiester, phosphorothioate, and p-ethoxy oligonucleotides - Google Patents

Liposomal phosphodiester, phosphorothioate, and p-ethoxy oligonucleotides

Info

Publication number
CA2228944A1
CA2228944A1 CA002228944A CA2228944A CA2228944A1 CA 2228944 A1 CA2228944 A1 CA 2228944A1 CA 002228944 A CA002228944 A CA 002228944A CA 2228944 A CA2228944 A CA 2228944A CA 2228944 A1 CA2228944 A1 CA 2228944A1
Authority
CA
Canada
Prior art keywords
oligonucleotide
composition
oligonucleotides
ethoxy
antisense
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
CA002228944A
Other languages
French (fr)
Other versions
CA2228944C (en
Inventor
Gabriel Lopez-Berestein
Ana Maria Tari
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
Individual
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 Individual filed Critical Individual
Publication of CA2228944A1 publication Critical patent/CA2228944A1/en
Application granted granted Critical
Publication of CA2228944C publication Critical patent/CA2228944C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
    • 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
    • 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
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates

Abstract

An improved delivery system for antisense oligonucleotides involves a liposomal composition, comprising a liposome which consists essentially of neutral phospholipids and an antisense oligonucleotide that is entrapped in the liposome and is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides.

Claims (12)

1. A liposomal composition of antisense oligonucleotides, including (a) a liposome which consists essentially of neutral phospholipids, and (b) an antisense oligonucleotide that is entrapped in the liposome and is selected from the groupconsisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides.
2. The composition of claim 1, where the phospholipids are phosphatidylcholines.
3. The composition of claim 1, where the phospholipids are dioleoylphosphatidyl choline.
4. The composition of claim 1, where the antisense oligonucleotide is a phosphodiester oligonucleotide, and the molar ratio of phospholipid to oligo is less than about 3,000:1.
5. The composition of claim 1, where the antisense oligonucleotide is a phosphorothioate oligonucleotide, and the molar ratio of phospholipid to oligo is between about 10:1 and about 50:1.
6. The composition of claim 1, where the antisense oligonucleotide is a p-ethoxy oligonucleotide, and the molar ratio of phospholipid to oligo is between about 5:1 and about 100:1.
7. The composition of claim 1, where the antisense oligonucleotide is a p-ethoxy oligonucleotide which consists essentially of a nucleic acid molecule having the sequence GAAGGGCTTCTGCGTC.
8. The composition of claim 1, where the antisense oligonucleotide is a p-ethoxy oligonucleotide which consists essentially of a nucleic acid molecule having the sequence CTGAAGGGCTTCTTCC.
9. The composition of claim 1, where the antisense oligonucleotide is a p-ethoxy oligonucleotide which consists essentially of a nucleic acid molecule having the sequence GGGCTTTTGAACTCTGCT.
10. A method of inhibiting the growth of tumor cells, including the step of administering to a mammalian subject having a tumor an amount effective to inhibit the growth of tumor cells of a composition that includes (a) a liposome which consists essentially of neutral phospholipids, and (b) an antisense oligonucleotide that is entrapped in the liposome and is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxyoligonucleotides.
11. A method of preparing a liposomal composition of antisense oligonucleotides, including the steps of:

(a) hydrating a lyophilized composition that consists essentially of neutral phospholipids and an antisense oligonucleotide that is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides, thereby forming an aqueous suspension which includes free oligonucleotide and liposomes entrapping oligonucleotide; and (b) separating the free oligonucleotide from the liposomes by dialysis.
12. The method of claim 11, where the aqueous suspension is sonicated before dialysis.
CA2228944A 1995-08-29 1996-08-26 Liposomal phosphodiester, phosphorothioate, and p-ethoxy oligonucleotides Expired - Fee Related CA2228944C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/520,385 1995-08-29
US08/520,385 US5855911A (en) 1995-08-29 1995-08-29 Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides
PCT/US1996/014146 WO1997007784A2 (en) 1995-08-29 1996-08-26 LIPOSOMAL PHOSPHODIESTER, PHOSPHOROTHIOATE, AND p-ETHOXY OLIGONUCLEOTIDES

Publications (2)

Publication Number Publication Date
CA2228944A1 true CA2228944A1 (en) 1997-03-06
CA2228944C CA2228944C (en) 2011-10-18

Family

ID=24072378

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2228944A Expired - Fee Related CA2228944C (en) 1995-08-29 1996-08-26 Liposomal phosphodiester, phosphorothioate, and p-ethoxy oligonucleotides

Country Status (11)

Country Link
US (4) US5855911A (en)
EP (1) EP0847272B1 (en)
JP (1) JP4291412B2 (en)
AT (1) ATE253897T1 (en)
AU (1) AU6912996A (en)
CA (1) CA2228944C (en)
DE (1) DE69630691T2 (en)
DK (1) DK0847272T3 (en)
ES (1) ES2210385T3 (en)
PT (1) PT847272E (en)
WO (1) WO1997007784A2 (en)

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US7754872B2 (en) 2010-07-13
US6042846A (en) 2000-03-28
ATE253897T1 (en) 2003-11-15
US20070202157A1 (en) 2007-08-30
AU6912996A (en) 1997-03-19
US20040005353A1 (en) 2004-01-08
JP4291412B2 (en) 2009-07-08
JPH11512099A (en) 1999-10-19
WO1997007784A2 (en) 1997-03-06
DE69630691D1 (en) 2003-12-18
ES2210385T3 (en) 2004-07-01
US7176302B2 (en) 2007-02-13
US5855911A (en) 1999-01-05
CA2228944C (en) 2011-10-18
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DE69630691T2 (en) 2004-11-25
EP0847272B1 (en) 2003-11-12

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