FI119738B - Komposition som innehåller en lösning av en nukleinsyra och en lösning av en katjonisk polymer och användningar - Google Patents

Komposition som innehåller en lösning av en nukleinsyra och en lösning av en katjonisk polymer och användningar Download PDF

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FI119738B
FI119738B FI970115A FI970115A FI119738B FI 119738 B FI119738 B FI 119738B FI 970115 A FI970115 A FI 970115A FI 970115 A FI970115 A FI 970115A FI 119738 B FI119738 B FI 119738B
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composition according
nucleic acid
polymer
cells
solution
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FI970115A
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FI970115A0 (sv
FI970115A (sv
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Daniel Scherman
Jean-Paul Behr
Otmane Boussif
Barbara Demeneix
Franck Lezoualch
Mojgan Mergny
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Aventis Pharma Sa
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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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Polyamides (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)

Claims (30)

1. Komposition, som innehäller en lösning av en nukleinsyra och en lösning av en katjonisk polymer, vilka 5 har kombinerats ooh homogeniserats, varvid den katjoniska polymeren har den allmänna formeIn {1}: _ r j av P väri - R kan vara en väteatom eller en grupp med formeln: •j-<CH2)n-N- L- J
2. Komposition enligt paten tkrav 1, k annetee k -nad ay att i formel (I) är n 2 - 5.
3. Komposition enligt patentkrav 1 eller 2, kän- netecknad av att polymerens genomsnittliga molekylvikt är 103 - 5 x 106 Da.
4. Komposition enligt nägot av patentkraven 1-3, kännetecknad av att polymeren väljs frän polyetyleni- 25 min (PEI) och polypropylenimin (PPI).
5. Komposition enligt patentkrav 4, känneteck- j nad av att polymeren väljs frän polyetylenimin, vars ge- \ nomsnittliga molekylvikt är 5.0 000 (PEI50K) , och frän po- lyetylenimin, vans genomsnittliga molekylvikt är 800 000 (PEI800K).
6. Komposition enligt patentkrav 5, kanne tec 3c -n a d av att förhällandet R är 5-15 .
7. Komposition enligt nägot av de föregäende pa- tentkraven, kännetecknad av att den omfattar ocksä ett eller flera tillsatsämnen, som fönuär bindas till ett polymer/nukleinsyrakoinplex ocli förbättra dess transfekti-onsförmäga, nar näitinda tillsatsäitine har valts fr&ti lipi- 10 der, proteiner, 1 ipopolyaminer och syntetislca polymerer.
8. Komposition enligt patentkrav 7, kännetecknad av att tillsatsämnet är en katjonisk lipid.
9. Komposition enligt patentkrav 8, kännetecknad av att den katjoniska lipiden är en eller flera lipo- 15 polyaminer.
10. Komposition enligt patentkrav 9, kännetecknad av att 1 ipopolyaminen motsvarar den allmänna forme In H?N- (- (CH)m-3NIH~) j-h, väri m är ett heltal 2-6 och 1, :är ett heltal 1 - 5, m Jean variera enligt oi ikä 3colgrup- 20 per som placerar sig mellan tvä aminer,
10 H - n är ett heitai 2 - 10; - p och g är heitai, och det är klart att summan p + q är sädan att polymerens genomsnittliga molekylvikt Sr 100 - 107 Da, och 15. polymerens och nukleinsyrans relative andelar har valts sä att förhällandet R polymerens aminer/nukleinsy-rans fosfater är 5~30.
11. Komposition enligt patentkrav 10, kännetecknad av att 1ipopolyaminet väljs fran dioktadekyla-midoglycylspermin. (POGS) eller 5-karboxispermylamid (DPPES) av palmitoylfosfatidyletanolamin.
12. Komposition enligt patentkrav 7, känne tecknad av att tillsatsämnet Sr en eller flera neutrala lipider.
13. Komposition enligt patentkrav 12, kännetecknad av att den neutrala lipiden eller de neutrala 30 lipiderna har valts Erän syntetiska eller naturliga; under fysiologiska förhällanden switterjoniska lipider eller lipider utan jonladdning.
14. Komposition enligt patentkrav 13, kanne -tecknad av att den neutrala lipiden eller de neutrala j 35 lipiderna omfattar 2 fettsyrakedjor. j
15. Komposition enligt pa tent kr av 13, känne -tecknad av att den neutrala lipiden eller de neutrala lipiderna vaijs fr&n dioleoylfosfatidyletanolamin {DOPE), oleoy lpalmi t oyl f o s f at i dyl et anoi amin (POPE) , distearoyl-, di- 5 palmitoyl- eller -dimyristoylfosfatidylatanolamin samt 1-3 gänger N-metylerade derivat; fosfatidylglyceroler, diacylglycero1er, glykocyldiacylglyceroler, cerebrocider (säsom framför allt galaktocerebrocider), sfingolipider (säsom framför allt sfingomyeliner) och asialogangliocider 10 (säsom framför allt asialoGMl och GM2),
16. Komposition enligt patentkrav 1, känne- tecknad av att nukleinsyran är deoxiribonukleinsyra.
17. Komposition enligt patentkrav 1, k anne- t e c k n a d av att nukleinsyran är ribonukleinsyra.
18. Komposition enligt patentkrav 16 eller 17, känne tecknad av att nukleinsyran är kemiskt modifie-rad.
19. Komposition enligt patentkrav 16 - 18, kanne tecknad av att nukleinsyran är en antisensenuklein- 20 syra.
20. Komposition enligt nägot av patentkraven 16 - 19, känne tecknad av att nukleinsyran innehäller en tera-peutisk gen.
21. Komposition enligt nägot av patentkraven 16 - 19, 25 känne tecknad av att nukleinsyran kodan för ett anti gen t protein.
22. Komposition enligt patentkrav k anne tecknad av att nukleinsyran kodar för ett virusprotein.
23. Komposition enligt patentkrav 7, känne- i 30 tecknad av att den omfattar 0,1 - 20 molara ekvivalen- : ter av tillsatsämnet per 1 mol ai" ekvi valent fosfat av nuk-leinsyra och företrädesvis 1-5.
24. Komposition enligt nägot av de föregäende patentkraven, känne tecknad av att den ocksä omfattar f 35 ett identifieringsställe, som bestär av socker och/eller ί peptid, säsom en antikropp eller dess fragment, en ligand i av en cells receptor eller dess fragment eller en receptor eller ett fragment av en receptor.
25. Komposition enligt patentkrav 24, kanne-tecknad av att identifieringsstället är kovalent bnndet 5 till en polymer enligt formel (I).
26. Komposition enligt nagot av de föregäende pa-tentkraven, kännetecknad av att den ocksä omfattar en farmaeeutisk godtagbar bärare för en formulering soro skall injiceras.
27. Komposition enligt nägot av de föregäende pa- tentkraven, känne tecknat av att den omfattar en far-maceutiskt godtagbar bärare för utstrykning pä huden ooh/eller slemhinnorna.
28. Komposition enligt nägot av patentkraven 1-27 15 att användas som läkemedel.
29. Komposition enligt nägot av pa tentkraven 1-27 att användas som vaccin.
30. Användning av en katjonisk polymer, säsom den definieras i patentkrav 1, för överföring av nukleinsyror 20 in vitro till cellerna. 1
FI970115A 1994-07-13 1997-01-10 Komposition som innehåller en lösning av en nukleinsyra och en lösning av en katjonisk polymer och användningar FI119738B (sv)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR9408735 1994-07-13
FR9408735A FR2722506B1 (fr) 1994-07-13 1994-07-13 Composition contenant des acides nucleiques, preparation et utilisations
PCT/FR1995/000914 WO1996002655A1 (fr) 1994-07-13 1995-07-07 Composition contenant des acides nucleiques, preparation et utilisations
FR9500914 1995-07-07

Publications (3)

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FI970115A0 FI970115A0 (sv) 1997-01-10
FI970115A FI970115A (sv) 1997-01-10
FI119738B true FI119738B (sv) 2009-02-27

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US (1) US6013240A (sv)
EP (1) EP0770140B1 (sv)
JP (1) JP4275728B2 (sv)
KR (1) KR100424802B1 (sv)
AT (1) ATE367448T1 (sv)
AU (1) AU2930795A (sv)
CA (1) CA2194797C (sv)
DE (1) DE69535540T9 (sv)
DK (1) DK0770140T3 (sv)
ES (1) ES2290952T3 (sv)
FI (1) FI119738B (sv)
FR (1) FR2722506B1 (sv)
IL (1) IL114566A (sv)
MX (1) MX9700270A (sv)
NO (1) NO323110B1 (sv)
PT (1) PT770140E (sv)
WO (1) WO1996002655A1 (sv)
ZA (1) ZA955849B (sv)

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JP4275728B2 (ja) 2009-06-10
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FI970115A (sv) 1997-01-10
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DE69535540T2 (de) 2008-06-19
EP0770140B1 (fr) 2007-07-18
US6013240A (en) 2000-01-11
IL114566A (en) 2005-08-31
MX9700270A (es) 1997-05-31
ZA955849B (en) 1996-02-21
DK0770140T3 (da) 2007-11-19
CA2194797A1 (fr) 1996-02-01
AU2930795A (en) 1996-02-16
JPH10502918A (ja) 1998-03-17
KR100424802B1 (ko) 2004-06-23
NO970049L (no) 1997-01-07
FR2722506B1 (fr) 1996-08-14
ATE367448T1 (de) 2007-08-15
NO970049D0 (no) 1997-01-07
KR970704889A (ko) 1997-09-06
ES2290952T3 (es) 2008-02-16
DE69535540D1 (de) 2007-08-30
PT770140E (pt) 2007-10-19
DE69535540T9 (de) 2012-03-15
NO323110B1 (no) 2007-01-02
CA2194797C (fr) 2010-03-23
IL114566A0 (en) 1995-11-27
WO1996002655A1 (fr) 1996-02-01

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