CA2577423A1 - Therapeutic uses of inhibitors of rtp801 - Google Patents

Therapeutic uses of inhibitors of rtp801 Download PDF

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Publication number
CA2577423A1
CA2577423A1 CA002577423A CA2577423A CA2577423A1 CA 2577423 A1 CA2577423 A1 CA 2577423A1 CA 002577423 A CA002577423 A CA 002577423A CA 2577423 A CA2577423 A CA 2577423A CA 2577423 A1 CA2577423 A1 CA 2577423A1
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Prior art keywords
use according
inhibitor
disorder
sequence
respiratory disorder
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Granted
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CA002577423A
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French (fr)
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CA2577423C (en
Inventor
Elena Feinstein
Klaus Giese
Joerg Kaufmann
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Silence Therapeutics GmbH
Quark Pharmaceuticals Inc
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Individual
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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
    • 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
    • C07H21/02—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 ribosyl as saccharide radical
    • 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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/054—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function
    • A01K2217/058—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function due to expression of inhibitory nucleic acid, e.g. siRNA, antisense
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0362—Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
    • 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
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • 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
    • C12N2310/321—2'-O-R Modification

Abstract

The present invention provides novel molecules, compositions, methods and uses for treating microvascular disorders, eye diseases and respiratory conditions based upon inhibition of the RTP801 gene and/or protein.

Claims (28)

1. ~A method of treating a patient suffering from a respiratory disorder, an eye disease, a microvascular disorder, or a spinal cord injury or disease which comprises administering to the patient a pharmaceutical composition comprising an RTP801 inhibitor in an amount effective to treat the patient.
2. ~A method according to claim 1, wherein the eye disease is macular degeneration.
3. ~A method according to claim 1, wherein the respiratory disorder is COPD.
4. ~A method according to claim 1, wherein the respiratory disorder is asthma.
5. ~A method according to claim 1, wherein the respiratory disorder is chronic bronchitis.
6. ~A method according to claim 1, wherein the respiratory disorder is emphysema.
7.~A method according to claim 1, wherein the microvascular disorder is diabetic retinopathy.
8. ~A method according to claim 1, wherein the microvascular disorder is acute renal failure.
9. ~The method according to any one of claims 1-8, wherein the inhibitor comprises a polynucleotide which comprises consecutive nucleotides having a sequence of sufficient length and homology to a sequence present within the sequence of the RTP801 gene set forth in SEQ ID NO:1 to permit hybridization of the inhibitor to the gene.
10. The method according to any one of claims 1-8, wherein the inhibitor comprises an antibody which specifically binds to an epitope present within a polypeptide which comprises consecutive amino acids, the sequence of which is set forth in Figure 2 (SEQ ID No:2).
11. A method for treating a patient suffering from a respiratory disorder, an eye disease, a microvascular disorder or a spinal cord injury or disease which comprises administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of a polynucleotide RTP801 inhibitor so as to thereby treat the patient.
12. A method according to claim 11, wherein the polynucleotide is siRNA.
13. The method according to claim 12, wherein the siRNA comprises consecutive nucleotides having a sequence identical to any one of the sequences set forth in any one of Tables A-C (SEQ ID NOs:3-344).
14. The method according to claim 11, wherein the inhibitor is selected from the group consisting of an siRNA molecule, a vector comprising an siRNA
molecule, a vector which can express an siRNA molecule and a molecule which is endogenously processed into an siRNA molecule.
15. Use of a therapeutically effective amount of an RTP801 inhibitor for the preparation of a medicament for promoting recovery in a patient suffering from a respiratory disorder, an eye disease, a microvascular disorder or spinal cord injury or disease..
16. The use according to claim 15, wherein the eye disease is macular degeneration.
17. The use according to claim 15, wherein the respiratory disorder is COPD.
18. The use according to claim 15, wherein the respiratory disorder is asthma.
19. The use according to claim 15, wherein the respiratory disorder is chronic bronchitis.
20. The use according to claim 15, wherein the respiratory disorder is emphysema.
21. The use according to claim 15, wherein the microvascular disorder is diabetic retinopathy.
22. The use according to claim 15, wherein the microvascular disorder is acute renal failure.
23. The use according to any one of claims 15-22, wherein the inhibitor comprises a polynucleotide which comprises consecutive nucleotides having a sequence of sufficient length and homology to a sequence present within the sequence of the RTP801 gene set forth in SEQ ID NO:1 to permit hybridization of the inhibitor to the gene.
24. The use according to any one of claims 15-22, wherein the RTP801 inhibitor is an antibody which specifically binds to an epitope present within a polypeptide which comprises consecutive amino acids, the sequence of which is set forth in Figure 2 (SEQ ID No:2).
25. The use according to any one of claims 15-22, wherein the polynucleotide down regulates the expression of gene RTP801.
26. The use according to any one of claims 15-22, wherein the polynucleotide is an siRNA.
27. The use according to claim 26, wherein the siRNA comprises consecutive nucleotides having a sequence identical to any one of the sequences set forth in any one of Tables A-C (SEQ ID NOs:3-344).
28. The use according to claim 25, wherein the inhibitor is selected from the group consisting of an siRNA molecule, a vector comprising an siRNA
molecule, a vector which can express an siRNA molecule and a molecule which is endogenously processed into an siRNA molecule.
CA2577423A 2004-08-16 2005-08-16 Therapeutic uses of inhibitors of rtp801 Expired - Fee Related CA2577423C (en)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
EP04019405 2004-08-16
EP04019405.2 2004-08-16
US60198304P 2004-08-17 2004-08-17
US60/601,983 2004-08-17
US60466804P 2004-08-25 2004-08-25
US60/604,668 2004-08-25
US60978604P 2004-09-14 2004-09-14
US60/609,786 2004-09-14
US63865904P 2004-12-22 2004-12-22
US60/638,659 2004-12-22
US66423605P 2005-03-22 2005-03-22
US60/664,236 2005-03-22
US68894305P 2005-06-08 2005-06-08
US60/688,943 2005-06-08
PCT/US2005/029236 WO2006023544A2 (en) 2004-08-16 2005-08-16 Therapeutic uses of inhibitors of rtp801

Publications (2)

Publication Number Publication Date
CA2577423A1 true CA2577423A1 (en) 2006-03-02
CA2577423C CA2577423C (en) 2012-11-06

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CA2577423A Expired - Fee Related CA2577423C (en) 2004-08-16 2005-08-16 Therapeutic uses of inhibitors of rtp801

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US (4) US7741299B2 (en)
EP (2) EP2319925B1 (en)
JP (1) JP4468989B2 (en)
KR (2) KR100939274B1 (en)
CN (1) CN101123994B (en)
AP (1) AP2007003921A0 (en)
AU (1) AU2005277508B2 (en)
BR (1) BRPI0514395A (en)
CA (1) CA2577423C (en)
DK (1) DK2319925T3 (en)
EA (1) EA012799B1 (en)
HK (1) HK1111088A1 (en)
IL (3) IL181238A (en)
MA (1) MA28802B1 (en)
MX (1) MX2007002043A (en)
NO (1) NO342934B1 (en)
NZ (1) NZ553162A (en)
PL (1) PL1791568T3 (en)
TN (1) TNSN07063A1 (en)
WO (1) WO2006023544A2 (en)

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