ES2566632T3 - Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm - Google Patents
Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm Download PDFInfo
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- ES2566632T3 ES2566632T3 ES12182257.1T ES12182257T ES2566632T3 ES 2566632 T3 ES2566632 T3 ES 2566632T3 ES 12182257 T ES12182257 T ES 12182257T ES 2566632 T3 ES2566632 T3 ES 2566632T3
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- 239000003814 drug Substances 0.000 title claims 6
- 229940079593 drug Drugs 0.000 title 1
- 108020004999 messenger RNA Proteins 0.000 title 1
- 108020004707 nucleic acids Proteins 0.000 title 1
- 150000007523 nucleic acids Chemical class 0.000 title 1
- 102000039446 nucleic acids Human genes 0.000 title 1
- 239000002243 precursor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 108010069091 Dystrophin Proteins 0.000 claims abstract 5
- 201000006938 muscular dystrophy Diseases 0.000 claims 4
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 102000001039 Dystrophin Human genes 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 abstract 3
- 125000003835 nucleoside group Chemical group 0.000 abstract 3
- 235000000346 sugar Nutrition 0.000 abstract 3
- 108091034117 Oligonucleotide Proteins 0.000 abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 abstract 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 238000012986 modification Methods 0.000 abstract 1
- 239000002773 nucleotide Substances 0.000 abstract 1
- 125000003729 nucleotide group Chemical group 0.000 abstract 1
- 150000008163 sugars Chemical class 0.000 abstract 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- 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
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
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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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/33—Alteration of splicing
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Abstract
Un compuesto capaz de inducir el salto del exón 46 del gen de la distrofina, que es (a) un oligonucleótido que consiste en la secuencia de nucleótidos mostrada en una cualquiera de las SEC ID Nº 21, 22, 19, 20 y 18, donde al menos uno de los azúcares que constituyen el oligonucleótido está modificado, y donde dicho azúcar es Dribofuranosa y al menos una modificación de dicho azúcar es 2'-O,4'-C-alquilenación de la D-ribofuranosa, o (b) un compuesto representado por la fórmula general (V'), (VI') y (VII') o una sal farmacológicamente aceptable del mismo, donde dichas fórmulas generales se definen del siguiente modo: BT'5-BM'5-BB'5 (V') donde BT'5 es un grupo representado por uno cualquiera de los siguientes (5a') a (5g'): (5a')HO-, (5b')HO-Bt-, (5c')HO-Bt-Bt-, (5d')HO-Bt-Bt-Bt-, (5e')HO-Bt-Bt-Bt-Bt-, (5f')HO-Bc-Bt-Bt-Bt-Bt-, o (5g')HO-Bg-Bc-Bt-Bt-Bt-Bt- BM'5 es un grupo representado por la siguiente fórmula (5'): -Bc-Bt-Bt-Bt-Bt-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc- (5') BB'5 es un grupo representado por uno cualquiera de los siguientes (52a') a (52i'): (52a')-CH2CH2OH, (52b')-Bt-CH2CH2OH, (52c')-Bt-Bc-CH2CH2OH, (52d')-Bt-Bc-Bt-CH2CH2OH, (52e')-Bt-Bc-Bt-Bt-CH2CH2OH, (52f')-Bt-Bc-Bt-Bt-Bt-CH2CH2OH, (52g')-Bt-Bc-Bt-Bt-Bt-Bt-CH2CH2OH, (52h')-Bt-Bc-Bt-Bt-Bt-Bt-Bc-CH2CH2OH, o (52i')-Bt-Bc-Bt-Bt-Bt-Bt-Bc-Bc-CH2CH2OH donde Bg es un grupo representado por la siguiente fórmula (G1) o (G2); Ba es un grupo representado por la siguiente fórmula (A1) o (A2); Bc es un grupo representado por la siguiente fórmula (C1) o (C2); y Bt es un grupo representado por la siguiente fórmula (U1) o (T2):**Fórmula** donde X es individual e independientemente un grupo representado por la siguiente fórmula (XI) o (X2): Y es individual e independientemente un átomo de hidrógeno, un grupo hidroxilo o un grupo alcoxi con 1-6 átomos de carbono; y Z es individual e independientemente un enlace sencillo o un grupo alquileno con 1-5 átomos de carbono; con la condición de que al menos uno de los nucleósidos que constituyen el compuesto representado por la fórmula (V') tenga un grupo 2'-O,4'-C-alquileno. BT'6-BM'6-BB'6 (VI') donde BT'6 es un grupo representado por uno cualquiera de los siguientes (6a') a (6r'): (6a')HO-, (6b')HO-Bc-, (6c')HO-Bt-Bc-, (6d')HO-Bc-Bt-Bc-, (6e')HO-Bg-Bc-Bt-Bc-, (6f')HO-Bt-Bg-Bc-Bt-Bc-, (6g')HO-Bc-Bt-Bg-Bc-Bt-Bc-, (6h')HO-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6j')HO-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6k')HO-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6l')HO-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6m')HO-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6n')HO-Bt-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6o')HO-Bt-Bt-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6p')HO-Bt-Bt-Bt-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, (6q')HO-Bt-Bt-Bt-Bt-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc-, or (6r')HO-Bc-Bt-Bt-Bt-Bt-Ba-Bg-Bt-Bt-Bg-Bc-Bt-Bg-Bc-Bt-Bc- BM'6 es un grupo representado por la siguiente fórmula (6'): -Bt-Bt-Bt-Bt-Bc-Bc- (6') BB'6 es un grupo representado por uno cualquiera de los siguientes (62a') a (62m'): (62a')-CH2CH2OH, (62b')-Ba-CH2CH2OH, (62c')-Ba-Bg-CH2CH2OH, (62d')-Ba-Bg-Bg-CH2CH2OH, (62e')-Ba-Bg-Bg-Bt-CH2CH2OH, (62f')-Ba-Bg-Bg-Bt-Bt-CH2CH2OH, (62g')-Ba-Bg-Bg-Bt-Bt-Bc-CH2CH2OH, (62h')-Ba-Bg-Bg-Bt-Bt-Bc-Ba-CH2CH2OH, (62i')-Ba-Bg-Bg-Bt-Bt-Bc-Ba-Ba-CH2CH2OH, (62j')-Ba-Bg-Bg-Bt-Bt-Bc-Ba-Ba-Bg-CH2CH2OH, (62k')-Ba-Bg-Bg-Bt-Bt-Bc-Ba-Ba-Bg-Bt-CH2CH2OH, (621')-Ba-Bg-Bg-Bt-Bt-Bc-Ba-Ba-Bg-Bt-Bg-CH2CH2OH, o (62m')-Ba-Bg-Bg-Bt-Bt-Bc-Ba-Ba-Bg-Bt-Bg-Bg-CH2CH2OH donde Bg, Ba, Bt y Bc son como se han definido anteriormente; con la condición de que al menos uno de los nucleósidos que constituyen el compuesto representado por la fórmula (VI') tenga un grupo 2' -O,4' -C-alquileno; BT'7-BM'7-BB'7 (VII') donde BT'7 es un grupo representado por uno cualquiera de los siguiente (7a') a (7f'): (7a')HO-, (7b')HO-Bt-, (7c')HO-Ba-Bt-, (7d')HO-Bt-Ba-Bt-, (7e')HO-Bt-5 Bt-Ba-Bt-, o (7f')HO-Bg-Bt-Bt-Ba-Bt- BM'7 es un grupo representado por la siguiente fórmula (7'): -Bc-Bt-Bg-Bc-Bt-Bt-Bc-Bc-Bt- Bc-Bc-Ba-Ba-Bc-Bc- (7') donde Bg, Ba, Bt y Bc son como se han definido anteriormente; BB'7 es un grupo representado por el siguiente (72a'): (72a')-CH2CH2OH con la condición de que al menos uno de los nucleósidos que constituyen el compuesto representado por la fórmula (VII') tenga un grupo 2'-O,4'-C-alquileno.
Description
o una sal farmacológicamente aceptable de los mismos:
[6] El compuesto de acuerdo con [5] donde dicha fórmula se selecciona entre:
HO-Ge2p-Ce2p-Te2p-Te2p-Te2p-Ump-Cmp-Ump-Ump-Ump-Ump-Amp-Gmp-Ump-Ump-Ge2p-Ce2p-Te2p-Ge2p-Ce2p-CH2CH2OH; HO-Ge2p-Ce2p-Te2p-Te2p-Te2p-Ums-Cms-Ums-Ums-Ums-Ums-Ams-Gms-Ums-Ums-Ge2p-Ce2p-Te2p-Ge2p-Ce2p-CH2CH2OH; HO-Ge2s-Ce2s-Te2s-Te2s-Te2s-Ums-Cms-Ums-Ums-Ums-Ums-Ams-Gms-Ums-Ums-Ge2s-Ce2s-Te2s-Ge2s-Ce2s-CH2CH2OH; HO-Cmp
8
Claims (5)
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imagen1 imagen2 imagen3 imagen4 imagen5 imagen6 - 6. El compuesto de acuerdo con la reivindicación 5 donde dicha fórmula se selecciona entre:HO-Ge2p-Ce2p-Te2p-Te2p-Te2p-Ump-Cmp-Ump-Ump-Ump-Ump-Amp-Gmp-Ump-Ump-Ge2p-Ce2p-Te2p-Ge2p-Ce2p-CH2CH2OH; HO-Ge2p-Ce2p-Te2p-Te2p-Te2p-Ums-Cms-Ums-Ums-Ums-Ums-Ams-Gms-Ums-Ums-Ge2p-Ce2p-Te2p-Ge2p-Ce2p-CH2CH2OH; HO5 Ge2s-Ce2s-Te2s-Te2s-Te2s-Ums-Cms-Ums-Ums-Ums-Ums-Ams-Gms-Ums-Ums-Ge2s-Ce2s-Te2s-Ge2s-Ce2s-CH2CH2OH; HO-CmpUmp-Ump-Ump-Ump-Ae2p-Ge2p-Te2p-Te2p-Ge2p-Ce2p-Te2p-Ge2p-Ce2p-Te2p-Ce2p-Te2p-Ump-Ump-Ump-Cmp-Cmp-CH2CH2OH; HO-Cms-Ums-Ums-Ums-Ums-Ae2p-Ge2p-Te2p-Te2p-Ge2p-Ce2p-Te2p-Ge2p-Ce2p-Te2p-Ce2p-Te2p-Ums-Ums-Ums-Cms-Cms-CH2CH2OH; HO-Cms-Ums-Ums-Ums-Ums-Ae2s-Ge2s-Te2s-Te2s-Ge2s-Ce2s-Te2s-Ge2s-Ce2s-Te2s-Ce2s-Te2s-Ums-Ums-Ums-CmsCms-CH2CH2OH; HO-Te2p-Te2p-Te2p-Te2p-Ce2p-Cmp-Amp-Gmp-Gmp-Ump-Ump-Cmp-Amp-Ae2p-Ge2p-Te2p-Ge2p-Ge2p10 CH2CH2OH; HO-Te2p-Te2p-Te2p-Te2p-Ce2p-Cms-Ams-Gms-Gms-Ums-Ums-Cms-Ams-Ae2p-Ge2p-Te2p-Ge2p-Ge2p-CH2CH2OH; HO-Te2s-Te2s-Te2s-Te2s-Ce2s-Cms-Ams-Gms-Gms-Ums-Ums-Cms-Ams-Ae2s-Ge2s-Te2s-Ge2s-Ge2s-CH2CH2OH; HO-Ce2p-Te2p-Ge2p-Ce2p-Te2p-Ump-Cmp-Cmp-Ump-Cmp-Ce2p-Ae2p-Ae2p-Ce2p-Ce2p-CH2CH2OH; HO-Ge2p-Te2p-Te2p-Ae2p-Te2p-Cmp-UmpGmp-Cmp-Ump-Ump-Cmp-Cmp-Ump-Cmp-Ce2p-Ae2p-Ae2p-Ce2p-Ce2p-CH2CH2OH; HO-Ce2p-Ump-Gmp-Ce2p-Ump-Ump-Ce2p-Ce2p-Ump-Ce2p-Ce2p-Amp-Amp-Ce2p-Ce2p-CH2CH2OH; HO-Ce2p-Te2p-Gmp-Ce2p-Te2p-Ump-Cmp-Ce2p-Ump-Cmp-Ce2p-Amp15 Amp-Ce2p-Ce2p-CH2CH2OH; HO-Ce2p-Te2p-Ge2p-Ce2p-Te2p-Ums-Cms-Cms-Ums-Cms-Ce2p-Ae2p-Ae2p-Ce2p-Ce2p-CH2CH2OH; HO-Ge2p-Te2p-Te2p-Ae2p-Te2p-Cms-Ums-Gms-Cms-Ums-Ums-Cms-Cms-Ums-Cms-Ce2p-Ae2p-Ae2p-Ce2p-Ce2p-CH2CH2OH; HO-Ce2s-Ums-Gms-Ce2s-Ums-Ums-Ce2s-Ce2s-Ums-Ce2s-Ce2s-Ams-Ams-Ce2s-Ce2s-CH2CH2OH; HO-Ce2s-Te2s-Gms-Ce2s-Te2s-UmsCms-Ce2s-Ums-Cms-Ce2s-Ams-Ams-Ce2s-Ce2s-CH2CH2OH; HO-Ce2s-Te2s-Ge2s-Ce2s-Te2s-Ums-Cms-Cms-Ums-Cms-Ce2s-Ae2s-Ae2s-Ce2s-Ce2s-CH2CH2OH; y HO-Ge2s-Te2s-Te2s-Ae2s-Te2s-Cms-Ums-Gms-Cms-Ums-Ums-Cms-Cms-Ums-Cms-Ce2s-Ae2s-Ae2s-Ce2s-Ce2s-CH2CH2OH.20 7. Un agente terapéutico para la distrofia muscular, que comprende el compuesto de una cualquiera de las reivindicaciones 1-6 o una sal farmacológicamente aceptable del mismo.25 8. El agente terapéutico de acuerdo con la reivindicación 7, cuya diana de tratamiento es aquellos pacientes en que la cantidad total de los aminoácidos en la fase de lectura abierta del gen de la distrofina será un múltiplo de 3 cuando el exón 46 del gen de la distrofina se ha saltado.
- 9. Un compuesto de acuerdo con una cualquiera de las reivindicaciones 1 a 6 o un agente terapéutico de acuerdo 30 con la reivindicación 7 u 8 para su uso en el tratamiento de la distrofia muscular.
- 10. Uso de un compuesto de acuerdo con una cualquiera de las reivindicaciones 1 a 6 en la fabricación de un medicamento para tratar la distrofia muscular.35 11. Uso de acuerdo con la reivindicación 10, donde la diana de tratamiento es aquellos pacientes en que la cantidad total de los aminoácidos en la fase de lectura abierta del gen de la distrofina será un múltiplo de 3 cuando el exón 46 del gen de la distrofina se ha saltado.
- 12. Un agente terapéutico de acuerdo con la reivindicación 7 u 8, un compuesto o agente terapéutico de acuerdo40 con la reivindicación 9 o un uso de acuerdo con la reivindicación 10 u 11 donde dicha distrofia muscular es distrofia muscular de Duchenne.42
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002340857 | 2002-11-25 | ||
| JP2002340857 | 2002-11-25 | ||
| JP2003204381 | 2003-07-31 | ||
| JP2003204381 | 2003-07-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2566632T3 true ES2566632T3 (es) | 2016-04-14 |
Family
ID=32396255
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12182257.1T Expired - Lifetime ES2566632T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES12182249.8T Expired - Lifetime ES2566628T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES12182258.9T Expired - Lifetime ES2554660T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES09011130.3T Expired - Lifetime ES2509140T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES11155689.0T Expired - Lifetime ES2561851T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES12182252.2T Expired - Lifetime ES2566629T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12182249.8T Expired - Lifetime ES2566628T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES12182258.9T Expired - Lifetime ES2554660T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
| ES09011130.3T Expired - Lifetime ES2509140T3 (es) | 2002-11-25 | 2003-11-21 | Fármacos de ácido nucleico ENA que modifican el corte y empalme en precursores de ARNm |
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| ES (6) | ES2566632T3 (es) |
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| WO2007123391A1 (en) | 2006-04-20 | 2007-11-01 | Academisch Ziekenhuis Leiden | Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly expressed gene. |
| EP1857548A1 (en) | 2006-05-19 | 2007-11-21 | Academisch Ziekenhuis Leiden | Means and method for inducing exon-skipping |
| DK2049664T3 (da) | 2006-08-11 | 2012-01-02 | Prosensa Technologies Bv | Enkeltstrengede oligonukleotider, som er komplementære til repetitive elementer, til behandling af med DNA-repetitiv-ustabilitet associerede lidelser |
| EP2167135A2 (en) * | 2007-07-12 | 2010-03-31 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs, tissues or tumor cells |
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| PL2203173T3 (pl) | 2007-10-26 | 2016-06-30 | Academisch Ziekenhuis Leiden | Środki i sposoby przeciwdziałania zaburzeniom mięśni |
| USRE48468E1 (en) | 2007-10-26 | 2021-03-16 | Biomarin Technologies B.V. | Means and methods for counteracting muscle disorders |
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- 2003-11-21 ES ES09011130.3T patent/ES2509140T3/es not_active Expired - Lifetime
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