CA2259144A1 - Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1 - Google Patents

Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

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Publication number
CA2259144A1
CA2259144A1 CA002259144A CA2259144A CA2259144A1 CA 2259144 A1 CA2259144 A1 CA 2259144A1 CA 002259144 A CA002259144 A CA 002259144A CA 2259144 A CA2259144 A CA 2259144A CA 2259144 A1 CA2259144 A1 CA 2259144A1
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CA
Canada
Prior art keywords
polynucleotide
composition
hybridizes
grb2
crk1
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
CA002259144A
Other languages
French (fr)
Other versions
CA2259144C (en
Inventor
Gabriel Lopez-Berestein
Ana M. Tari
Ralph B. Arlinghaus
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University of Texas System
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Individual
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Filing date
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Application filed by Individual filed Critical Individual
Priority to CA2741501A priority Critical patent/CA2741501A1/en
Publication of CA2259144A1 publication Critical patent/CA2259144A1/en
Application granted granted Critical
Publication of CA2259144C publication Critical patent/CA2259144C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • 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
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/111—Antisense spanning the whole gene, or a large part of it
    • 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
    • C12N2310/311—Phosphotriesters
    • 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
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention provides novel compositions and methods for use in the treatment of cancer, specifically, in the treatment of chronic myelogenous leukemia (CML). The compositions contain antisense oligonucleotides that hybridize to Grb2 and Crk1 nucleic acids, the gene products of which are known to interact with the tumorigenic protein bcr-abl. Used alone, in conjunction with each other, and even in conjunction with antisense oligonucleotides directed to bcr-abl nucleic acids, these compositions inhibit the proliferation of CML cancer cells.

Claims (26)

1. A composition comprising a polynucleotide that hybridizes to the translation initiation site of a Grb2-encoding polynucleotide.
2. A composition comprising a polynucleotide that hybridizes to the translation initiation site of a Crkl-encoding polynucleotide.
3. The composition of claim 1, wherein said polynucleotide is an oligonucleotide having a length of 8-50 bases.
4. The composition of claim 2, wherein said polynucleotide is an oligonucleotide having a length of 8-50 bases.
5. The composition of claim 1, wherein the polynucleotide is an oligonucleotide having the sequence ATATTTGGCGATGGCTTC (SEQ ID NO: 5).
6. The composition of claim 2, wherein the polynucleotide is an oligonucleotide having the sequence GTCGAACCGGCGGAGGA (SEQ ID NO: 6).
7. The composition of claim 1, further comprising a liposome in which said polynucleotide is encapsulated.
8. The composition of claim 2, further comprising a liposome in which said polynucleotide is encapsulated.
9. The composition of claim 7, wherein said liposome comprises the lipid dioleoylphosphatidylcholine.
10. The composition of claim 8, wherein said liposome comprises the lipid dioleoylphosphatidylcholine.
11. A composition comprising (i) a polynucleotide that hybridizes to a Grb2-encoding polynucleotide or (ii) a polynucleotide that hybridizes to a Crk1-encoding polynucleotide.
12. The composition of claim 11, further comprising a polynucleotide that hybridizes to a bcr-abl-encoding polynucleotide.
13. A composition comprising an expression construct that encodes a first polynucleotide that hybridizes to the translation start site of a Grb2-encoding polynucleotide, wherein said first polynucleotide is under the control of a promoter that is active in eukaryotic cells.
14. A composition comprising an expression construct that encodes a first polynucleotide that hybridizes to the translation start site of a Crk1-encoding polynucleotide, wherein said first polynucleotide is under the control of a promoter that is active in eukaryotic cells.
15. A method for inhibiting proliferation of a cancer cell comprising contacting said cancer cell with a composition comprising at least (i) a polynucleotide that hybridizes to the translation start site of a Grb2 nucleic acid or (ii) a polynucleotide that hybridizes to the translation start site of a Crk1 nucleic acid.
16. The method of claim 15, wherein said polynucleotides are oligonucleotides having a length of 8-50 bases.
17. The method of claim 16, wherein said composition further comprises a polynucleotide that hybridizes to a bcr-abl nucleic acid.
18. The method of claim 17 wherein said composition comprises both (i) a polynucleotide that hybridizes to the translation start site of a Grb2 nucleic acid or (ii) a polynucleotide that hybridizes to the translation start site of a Crk1 nucleic acid.
19. The method of claim 16, wherein said cancer cell is a leukemia cell.
20. The method of claim 19, wherein said cancer cell is a chronic myelogenous leukemia cell.
21. The method of claim 16, wherein said composition further comprises a liposome in which said polynucleotide is encapsulated.
22. The method of claim 16, wherein said contacting takes place in a patient.
23. The method of claim 22, wherein said patient is a human.
24. The method of claim 22, wherein said composition is delivered to said human in a volume of 0.50-10.0 ml per dose.
25. The method of claim 22, wherein said composition is delivered to said human in an amount of 5-30 mg polynucleotide per m2.
26. The method of claim 25, wherein said composition is administered three times per week for eight weeks.
CA2259144A 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1 Expired - Fee Related CA2259144C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2741501A CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/679,437 1996-07-08
US08/679,437 US7309692B1 (en) 1996-07-08 1996-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to GRB2 or CRK1
PCT/US1997/010101 WO1998001547A1 (en) 1996-07-08 1997-07-08 INHIBITION OF CHRONIC MYELOGENOUS LEUKEMIC CELL GROWTH BY LIPOSOMAL-ANTISENSE OLIGODEOXY-NUCLEOTIDES TARGETING TO Grb2 OR Crk1

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CA2741501A Division CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Publications (2)

Publication Number Publication Date
CA2259144A1 true CA2259144A1 (en) 1998-01-15
CA2259144C CA2259144C (en) 2011-09-20

Family

ID=24726909

Family Applications (2)

Application Number Title Priority Date Filing Date
CA2741501A Abandoned CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1
CA2259144A Expired - Fee Related CA2259144C (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CA2741501A Abandoned CA2741501A1 (en) 1996-07-08 1997-07-08 Inhibition of chronic myelogenous leukemic cell growth by liposomal-antisense oligodeoxy-nucleotides targeting to grb2 or crk1

Country Status (9)

Country Link
US (3) US7309692B1 (en)
EP (2) EP0912729B1 (en)
JP (1) JP2000514438A (en)
AT (2) ATE383422T1 (en)
AU (1) AU740289B2 (en)
CA (2) CA2741501A1 (en)
DE (2) DE69736290T2 (en)
ES (2) ES2268731T3 (en)
WO (1) WO1998001547A1 (en)

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US8900627B2 (en) * 2008-06-06 2014-12-02 Mirna Therapeutics, Inc. Compositions for the in vivo delivery of RNAi agents
BRPI0915718A2 (en) * 2008-06-20 2017-06-20 Univ Texas crkl steering peptides
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BR112019005166A2 (en) * 2016-09-16 2019-07-02 Bio Path Holding Inc combination therapy with liposomal antisense oligonucleotides
JP7237009B2 (en) 2017-04-19 2023-03-10 バイオ－パス ホールディングス， インコーポレイテッド P-ethoxy nucleic acids for STAT3 inhibition

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Also Published As

Publication number Publication date
AU740289B2 (en) 2001-11-01
EP0912729A1 (en) 1999-05-06
JP2000514438A (en) 2000-10-31
EP0912729B1 (en) 2006-07-05
DE69736290D1 (en) 2006-08-17
EP1234876A1 (en) 2002-08-28
WO1998001547A1 (en) 1998-01-15
DE69738459D1 (en) 2008-02-21
ES2268731T3 (en) 2007-03-16
US7923548B2 (en) 2011-04-12
ATE383422T1 (en) 2008-01-15
AU3569497A (en) 1998-02-02
US20070238686A1 (en) 2007-10-11
ATE332369T1 (en) 2006-07-15
DE69736290T2 (en) 2007-07-05
DE69738459T2 (en) 2008-12-24
US7309692B1 (en) 2007-12-18
EP1234876B1 (en) 2008-01-09
US20030153526A1 (en) 2003-08-14
CA2259144C (en) 2011-09-20
US7220853B2 (en) 2007-05-22
CA2741501A1 (en) 1998-01-15
ES2299536T3 (en) 2008-06-01

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