WO2002055692A2 - Verfahren zur hemmung der expression eines zielgens und medikament zur therapie einer tumorerkrankung - Google Patents
Verfahren zur hemmung der expression eines zielgens und medikament zur therapie einer tumorerkrankung Download PDFInfo
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- WO2002055692A2 WO2002055692A2 PCT/EP2002/000151 EP0200151W WO02055692A2 WO 2002055692 A2 WO2002055692 A2 WO 2002055692A2 EP 0200151 W EP0200151 W EP 0200151W WO 02055692 A2 WO02055692 A2 WO 02055692A2
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- 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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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- 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
- C12N15/1131—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 viruses
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
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- C12N2310/3511—Conjugate intercalating or cleaving agent
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
Definitions
- the invention relates to a method for inhibiting the expression of at least one target gene in a cell and a medicament for the therapy of a tumor disease.
- a method for inhibiting the expression of a target gene by means of a double-stranded oligoribonucleotide is known from WO 99/32619.
- the known method aims at inhibiting the expression of genes in cells of invertebrates. For this it is necessary that the double-stranded oligoribonucleotide has a sequence identical to the target gene with a length of at least 25 bases.
- a method for inhibiting the expression of a target gene in a cell and a medicament are known from WO 00/44895.
- an oligoribonucleotide with a double-stranded structure (dsRNA) is introduced into the cell.
- a strand of the dsRNA has a region which, at least in sections, is complementary to the target gene and consists of at most 49 successive nucleotide pairs.
- the medicament contains at least one dsRNA for inhibiting the expression of a given target gene, a strand of the dsRNA being at least partially complementary to the target gene.
- the single-stranded oligonucleotides used can be rapidly broken down in the serum.
- the high amount of oligonucleotides is necessary because an antisense oligonucleotide must ultimately be introduced into target cells in an amount which is at least as large as the amount of the RNA of the target gene present there.
- the method only achieved a reduction in growth, but not a regression of the tumors.
- the object of the present invention is to eliminate the disadvantages of the prior art.
- a method and a medicament are to be specified with which the proliferation of tumor cells can be inhibited effectively and inexpensively.
- a method for inhibiting the apoptosis of a tumor cell inhibiting or preventing expression of at least one target gene wherein at least one double-stranded ribonucleic acid (dsRNA) is introduced into the tumor cell, one strand of which is complementary to the target gene, at least in sections, from less has a region consisting of 25 consecutive nucleotides.
- the "target gene” is the DNA strand of the double-stranded DNA in the tumor cell, which is complementary to a DNA strand which serves as a template for transcription, including all transcribed regions. The target gene is therefore generally the sense strand.
- the strand S1 can thus be complementary to an RNA transcript formed during the expression of the target gene or its processing product, such as an mRNA.
- a dsRNA is present when the ribonucleic acid consisting of one or two ribonucleic acid strands has a double-stranded structure. Not all nucleotides of the dsRNA need to have Watson-Crick base pairings. In particular, individual non-complementary base pairs have little or no effect on the process. The maximum possible number of base pairs is the number of nucleotides in the shortest strand contained in the dsRNA. "To be introduced” is understood to mean the absorption into the cell. It can be picked up by the cell itself. However, it can also be imparted by means of auxiliary substances or aids.
- the control dsRNA is a dsRNA which has no strand complementary to a gene occurring in the cells. It has proven to be particularly advantageous if at least one end of the dsRNA has a single-stranded overhang formed from 1 to 4, in particular 2 or 3, nucleotides. Such a dsRNA has a better effectiveness in inhibiting the expression of the target gene at least at one end than a dsRNA without single-stranded overhangs. One end is a region of the dsRNA in which there is a 5 'and a 3' strand end. A dsRNA consisting only of strand S1 accordingly has a loop structure and only one end. A dsRNA formed from the strand S1 and a strand S2 has two ends. One end is formed in each case by one end of strand S1 and one end of strand S2.
- the single-stranded overhang is preferably located at the 3 'end of the strand S1. This localization of the single-stranded overhang leads to a further increase in the efficiency of the method.
- the dsRNA has a single-stranded overhang only at one end, in particular at the end located at the 3 'end of the strand S1. The other end is smooth on a double ended dsRNA, i.e. without overhangs, trained. Such a dsRNA has proven to be particularly stable both in various cell culture media and in blood serum.
- the complementary region of the dsRNA can have 19 to 24, preferably 21 to 23, in particular 22, nucleotides.
- a dsRNA with this structure is particularly efficient in holding the target gene.
- the strand S1 of the dsRNA can have less than 30, preferably less than 25, particularly preferably 21 to 24, nucleotides. The number of these nucleotides is also the maximum number of base pairs possible in the dsRNA.
- At least one end of the dsRNA can be modified to counteract degradation in the tumor cell or dissociation of the double-stranded structure.
- the cohesion of the double-stranded structure brought about by complementary nucleotide pairs can be increased by at least one, preferably two, further chemical linkage (s).
- the chemical linkage can be formed by a covalent or ionic bond, a hydrogen bond, hydrophobic interactions, preferably van der Waals or stacking interactions, or by metal ion coordination. It can also be formed by purine analogs used in the double-stranded structure instead of purines.
- the target gene is at least one gene from the Bcl-2 family, in particular Bcl-2, Bcl-w or Bcl-xL. It is also possible that several genes are target genes. Both Bcl-2 and Bcl-xL can be target genes.
- the inhibition of the genes of the Bcl-2 family is particularly beneficial because their increased expression is related to the development and proliferation of many tumor cells.
- the inhibition of multiple target genes is advantageous because there are tumor cells that express multiple anti-apoptotic genes.
- the dsRNA preferably consists of a strand S2 with the sequence SEQ ID NO: 1 and the strand S1 with the sequence SEQ ID NO: 2 or a strand S2 with the sequence SEQ ID NO: 3 and the strand S1 with the sequence SEQ ID NO : 4 according to the attached sequence listing.
- a dsRNA is particularly effective in inhibiting the expression of the target gene Bcl-2.
- the tumor cell can be a pancreatic carcinoma cell.
- a micellar structure surrounding the dsRNA preferably a liposo, or a capsid enclosing the dsRNA can be used.
- the capsid can in particular be a viral natural capsid or an artificial capsid produced by chemical or enzymatic means or a structure derived therefrom.
- the invention relates to a medicament for the therapy of a tumor disease, which contains at least one double-stranded ribonucleic acid (dsRNA) for the inhibition of expression of at least one target gene, wherein a strand S1 of the dsRNA consists of fewer than 25 consecutive nucleotides which are at least partially complementary to the target gene Area.
- the target gene is a gene whose expression inhibits or prevents apoptosis of tumor cells.
- the drug should be dosed so that the inhibition of expression of at least one target gene can be achieved.
- a dosage of 5 mg dsRNA per kilogram of body weight and day is sufficient to achieve an inhibition or complete suppression of the expression of the target gene in the tumor cells. With such a low dosage, side effects are largely excluded.
- At least one end of the dsRNA preferably has a single-stranded overhang formed from 1 to 4, in particular 2 or 3, nucleotides.
- the single-stranded overhang can be located at the 3 'end of the strand S1.
- the dsRNA particularly preferably has a single-stranded overhang only at one end, in particular at the end located at the 3 'end of the strand S1 on. It has been found that such a dsRNA is particularly stable in the body. It is broken down or excreted more slowly in blood than a dsRNA with single-stranded overhangs at both ends. This enables a low dosage.
- the complementary region can have 19 to 24, preferably 21 to 23, in particular 22, nucleotides.
- the strand S1 can have less than 30, preferably less than 25, particularly preferably 21 to 24, nucleotides.
- at least one end of the dsRNA is modified to counteract degradation in the tumor cells or dissociation.
- the cohesion of the double-stranded structure brought about by complementary nucleotide pairs can be increased by at least one, preferably two, further chemical linkages.
- the target gene is preferably at least one gene from the Bcl-2 family, in particular Bcl-2, Bcl-w or Bcl-xL.
- a drug is particularly efficient which has a dsRNA which is specific both for the target gene Bcl-2 and for the target gene Bcl-xL.
- the dsRNA can consist of a strand S2 with the sequence SEQ ID NO: 1 and the strand S1 with the sequence SEQ ID NO: 2 or a strand S2 with the sequence SEQ ID NO: 3 and the strand S1 with the sequence SEQ ID NO: 4 exist according to the attached sequence listing.
- the tumor disease to be treated with the drug can be pancreatic cancer. So far, there has not been a sufficiently successful therapy for pancreatic carcinoma. The 5-year survival rate is around 3% and is the lowest of all cancers.
- the dsRNA can be present in the drug in a solution or of a micellar structure, preferably enclosed in a liposome or capsid.
- a micellar structure or a capsid can facilitate the uptake of the dsRNA into the tumor cells.
- the medicament can have a preparation which is suitable for inhalation, oral intake or injection, in particular for intravenous or intraperitoneal injection or for injection directly into a tumor tissue.
- a preparation suitable for inhalation or injection can consist of a physiologically compatible buffer, in particular a phosphate-buffered saline solution, and the dsRNA. It has surprisingly been found that a dsRNA which is only dissolved in such a buffer is taken up by the tumor cells and inhibits the expression of the target gene without the dsRNA having to be packaged in a special vehicle.
- FIG. 3 shows the percentage apoptosis rate of YAP C cells 120 hours after transfection with a dsRNA 3 complementary to a sequence from the noemycin resistance gene.
- Cells of the human pancreatic carcinoma cell line YAP C which can be obtained under the number ACC 382 from the German Collection of Microorganisms and Cell Cultures, Braunschweig, were under constant conditions at 37 ° C, 5% C0 2 in RPMI 1640 medium (Biochrom , Berlin) with 10% fetal calf serum (FKS) and 1% penicillin / streptomycin.
- Human skin fibroblasts were cultured under the same conditions in Dulbecco's MEM with 10% FCS and 1% penicillin / streptomycin.
- the double-stranded oligoribonucleotides used for transfections have the following sequences, designated SEQ ID NO: 1 to SEQ ID NO: 6 in the sequence listing:
- dsRNA 1 which is complementary to a first sequence from the human Bcl-2 gene:
- S2 5'- cag gac cuc gcc gcu gca gac c-3 '(SEQ ID NO: 1)
- Sl 3'-cg guc cug gag egg ega cgu eug g-5' (SEQ ID NO: 2)
- dsRNA 2 which is complementary to a second sequence from the human Bcl-2 gene:
- dsRNA 3 which is complementary to a sequence from the neomycin resistance gene:
- 10 ⁇ l of the double-stranded oligoribonucleotide (0.1-10 ⁇ M) were diluted with 175 ⁇ l cell culture medium without additives.
- 3 ul oligofectamines were diluted with 12 ul cell culture medium without additives and incubated for 10 minutes at room temperature.
- the oligofectamine thus diluted was added to the already diluted double-stranded oligoribonucleotides, mixed and incubated for 20 minutes at room temperature.
- the cells to be transfected were washed once with cell culture medium without additives and 800 ⁇ l of fresh cell culture medium were added.
- the double-stranded oligoribonucleotides dsRNA 1 and dsRNA 2 reduce the Bcl-2-mediated inhibition of apoptosis in the human pancreatic carcinoma cells examined. No additional stimulation of apoptosis is required to trigger or initiate apoptosis. The apoptosis rate increased depending on the incubation period.
- FIG. 1 shows that with dsRNA 1 and FIG. 2 shows the result achieved with dsRNA 2.
- skin fibroblasts were also transfected as non-transformed cells with dsRNAs 1 and 2. These cells showed no significant increase in apoptosis rate after 120 hours.
Abstract
Description
Claims
Priority Applications (45)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10163098A DE10163098B4 (de) | 2001-10-12 | 2001-12-20 | Verfahren zur Hemmung der Replikation von Viren |
DE50214266T DE50214266D1 (de) | 2001-01-09 | 2002-01-09 | Verfahren zur hemmung der expression eines zielgens und medikament zur therapie einer tumorerkrankung |
CA002432341A CA2432341A1 (en) | 2001-01-09 | 2002-01-09 | Method for inhibiting the expression of a target gene and medicament for treating a tumor disease |
JP2002556739A JP4209678B2 (ja) | 2001-01-09 | 2002-01-09 | 標的遺伝子の発現を阻害する方法および腫瘍を治療するための医薬 |
EP02702247A EP1349927B1 (de) | 2001-01-09 | 2002-01-09 | Verfahren zur hemmung der expression eines zielgens und medikament zur therapie einer tumorerkrankung |
AT02702247T ATE460481T1 (de) | 2001-01-09 | 2002-01-09 | Verfahren zur hemmung der expression eines zielgens und medikament zur therapie einer tumorerkrankung |
DE10230996A DE10230996A1 (de) | 2001-10-26 | 2002-07-09 | Medikament zur Behandlung eines Pankreaskarzinoms |
DE10230997A DE10230997A1 (de) | 2001-10-26 | 2002-07-09 | Medikament zur Erhöhung der Wirksamkeit eines Rezeptor-vermittelt Apoptose in Tumorzellen auslösenden Arzneimittels |
PCT/EP2002/011432 WO2003033700A1 (de) | 2001-10-12 | 2002-10-11 | Verfahren zur hemmung der replikation von viren |
PCT/EP2002/011971 WO2003035082A1 (de) | 2001-10-26 | 2002-10-25 | Medikament zur hemmung der expression eines zielgens |
EP02785313A EP1438409A1 (de) | 2001-10-26 | 2002-10-25 | Verwendung einer doppelsträngigen ribonukleinsäure zur behandlung einer infektion mit einem (+)-strang-rna-virus |
EP10011813.2A EP2264173A3 (de) | 2001-01-09 | 2002-10-25 | Verwendung einer doppelsträngigen Ribonukleinsäure zur gezielten Hemmung der Expression eines vorgegebenen Zielgens |
PCT/EP2002/011970 WO2003035870A1 (de) | 2001-10-26 | 2002-10-25 | Medikament zur behandlung eines pankreaskarzinoms |
US10/493,768 US20040248835A1 (en) | 2001-10-26 | 2002-10-25 | Use of a double-stranded ribonucleic acid for treating an infection with a positivestrand rna-virus |
US10/493,686 US20050119202A1 (en) | 2001-10-26 | 2002-10-25 | Medicament to treat a fibrotic disease |
PCT/EP2002/011973 WO2003035876A1 (de) | 2001-10-26 | 2002-10-25 | Verwendung einer doppelsträngigen ribonukleinsäure zur behandlung einer infektion mit einem (+)-strang-rna-virus |
CNA028251636A CN1604783A (zh) | 2001-10-26 | 2002-10-25 | 通过rna干扰治疗纤维化疾病的药物 |
PCT/EP2002/011972 WO2003035083A1 (de) | 2001-10-26 | 2002-10-25 | Medikament zur behandlung einer fibrotischen erkrankung durch rna interferenz |
JP2003538370A JP2005506385A (ja) | 2001-10-26 | 2002-10-25 | 膵臓癌を処置するための医薬 |
PCT/EP2002/011969 WO2003035869A1 (de) | 2001-10-26 | 2002-10-25 | Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens |
CNA028261798A CN1608131A (zh) | 2001-10-26 | 2002-10-25 | 治疗胰腺癌的药物 |
EP02801917A EP1438056A1 (de) | 2001-10-26 | 2002-10-25 | Medikament zur behandlung einer fibrotischen erkrankung durch rna interferenz |
CNA02826181XA CN1608133A (zh) | 2001-10-26 | 2002-10-25 | 双链核糖核酸用于治疗正(+)链rna病毒感染的用途 |
PCT/EP2002/011968 WO2003035868A1 (de) | 2001-10-26 | 2002-10-25 | Medikament zur erhöhung der wirksamkeit eines rezeptor-vermittelt apoptose in tumorzellen auslösenden arzeimittels |
EP02785312A EP1438406A1 (de) | 2001-10-26 | 2002-10-25 | Medikament zur behandlung eines pankreaskarzinoms |
JP2003538376A JP2005506087A (ja) | 2001-10-26 | 2002-10-25 | プラス鎖rnaウイルスによる感染症を処置するための2本鎖リボ核酸の使用 |
JP2003537650A JP2005512976A (ja) | 2001-10-26 | 2002-10-25 | Rna干渉により線維化疾患を処置するための医薬 |
EP02779511A EP1438405A1 (de) | 2001-01-09 | 2002-10-25 | Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens |
US10/384,512 US7348314B2 (en) | 2001-10-12 | 2003-03-07 | Compositions and methods for inhibiting viral replication |
US10/384,260 US7473525B2 (en) | 2001-01-09 | 2003-03-07 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US10/384,463 US7763590B2 (en) | 2001-10-12 | 2003-03-07 | Compositions and methods for inhibiting expression of a mutant gene |
US10/384,434 US20040121348A1 (en) | 2001-10-26 | 2003-03-07 | Compositions and methods for treating pancreatic cancer |
US10/382,634 US20040038921A1 (en) | 2001-10-26 | 2003-08-11 | Composition and method for inhibiting expression of a target gene |
US10/666,458 US20040126791A1 (en) | 2001-10-26 | 2003-09-19 | Compositions and methods for treating trail-resistant cancer cells |
US10/941,663 US7767802B2 (en) | 2001-01-09 | 2004-09-15 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US11/229,183 US7423142B2 (en) | 2001-01-09 | 2005-09-15 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US11/747,549 US20080070856A1 (en) | 2001-10-26 | 2007-05-11 | Medicament to treat a fibrotic disease |
US11/959,936 US7745418B2 (en) | 2001-10-12 | 2007-12-19 | Compositions and methods for inhibiting viral replication |
US12/175,938 US7868160B2 (en) | 2001-01-09 | 2008-07-18 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US12/631,689 US8273868B2 (en) | 2001-10-12 | 2009-12-04 | Compositions and methods for inhibiting viral replication |
US12/817,009 US7994309B2 (en) | 2001-10-26 | 2010-06-16 | Compositions and methods for inhibiting expression of a mutant gene |
US12/961,337 US8143390B2 (en) | 2001-01-09 | 2010-12-06 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US13/177,316 US8273870B2 (en) | 2001-10-26 | 2011-07-06 | Compositions and methods for inhibiting expression of a mutant gene |
US13/594,140 US20120322858A1 (en) | 2001-10-26 | 2012-08-24 | Compositions and Methods for Inhibiting Expression of a Mutant Gene |
US13/594,150 US20130064879A1 (en) | 2001-10-12 | 2012-08-24 | Compositions and Methods for Inhibiting Viral Replication |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10100586A DE10100586C1 (de) | 2001-01-09 | 2001-01-09 | Verfahren zur Hemmung der Expression eines Ziegens |
DE10100586.5 | 2001-01-09 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2002/000012 Continuation WO2002053672A1 (de) | 2001-01-04 | 2002-01-03 | Holzwerkstoffe aus mit polyisocyanaten verleimten holzteilen |
Related Child Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2002/000152 Continuation WO2002055693A2 (de) | 1999-11-24 | 2002-01-09 | Verfahren zur hemmung der expression eines zielgens |
PCT/EP2002/011969 Continuation WO2003035869A1 (de) | 2001-01-09 | 2002-10-25 | Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens |
US10/384,260 Continuation-In-Part US7473525B2 (en) | 2001-01-09 | 2003-03-07 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US10/384,260 Continuation US7473525B2 (en) | 2001-01-09 | 2003-03-07 | Compositions and methods for inhibiting expression of anti-apoptotic genes |
Publications (2)
Publication Number | Publication Date |
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WO2002055692A2 true WO2002055692A2 (de) | 2002-07-18 |
WO2002055692A3 WO2002055692A3 (de) | 2003-06-12 |
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---|---|---|---|---|
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US7399586B2 (en) | 2002-05-23 | 2008-07-15 | Ceptyr, Inc. | Modulation of biological signal transduction by RNA interference |
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WO2008116094A2 (en) | 2007-03-21 | 2008-09-25 | Brookhaven Science Associates, Llc | Combined hairpin-antisense compositions and methods for modulating expression |
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US7655768B2 (en) | 2004-08-26 | 2010-02-02 | Nippon Shinyaku Co., Ltd. | Galactose derivative, drug carrier and medicinal composition |
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US7745418B2 (en) | 2001-10-12 | 2010-06-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting viral replication |
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US7829693B2 (en) | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
US7858769B2 (en) | 2004-02-10 | 2010-12-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional siNA) |
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US8101742B2 (en) | 1999-01-30 | 2012-01-24 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
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US9074213B2 (en) | 2001-01-09 | 2015-07-07 | Alnylam Pharmacuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
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Families Citing this family (114)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5898031A (en) * | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US20040147022A1 (en) * | 1996-06-06 | 2004-07-29 | Baker Brenda F. | 2'-methoxy substituted oligomeric compounds and compositions for use in gene modulations |
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US8202846B2 (en) * | 2000-03-16 | 2012-06-19 | Cold Spring Harbor Laboratory | Methods and compositions for RNA interference |
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US7423142B2 (en) | 2001-01-09 | 2008-09-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US20040019001A1 (en) * | 2002-02-20 | 2004-01-29 | Mcswiggen James A. | RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA |
US20050176025A1 (en) * | 2001-05-18 | 2005-08-11 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA) |
US20050196767A1 (en) * | 2001-05-18 | 2005-09-08 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acis (siNA) |
US20050182007A1 (en) * | 2001-05-18 | 2005-08-18 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA) |
US20050203040A1 (en) * | 2001-05-18 | 2005-09-15 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA) |
US20050196765A1 (en) * | 2001-05-18 | 2005-09-08 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of checkpoint Kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA) |
US20050143333A1 (en) * | 2001-05-18 | 2005-06-30 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA) |
US20050158735A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of proliferating cell nuclear antigen (PCNA) gene expression using short interfering nucleic acid (siNA) |
US20050288242A1 (en) * | 2001-05-18 | 2005-12-29 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of RAS gene expression using short interfering nucleic acid (siNA) |
US20050159381A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of chromosome translocation gene expression using short interfering nucleic acid (siNA) |
US20050159382A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA) |
US20050233997A1 (en) * | 2001-05-18 | 2005-10-20 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA) |
US20050124566A1 (en) * | 2001-05-18 | 2005-06-09 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA) |
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US20050245492A1 (en) | 2004-04-28 | 2005-11-03 | Lephart Edwin D | Use of equol for treating skin diseases |
EP1572956A2 (de) | 2002-08-01 | 2005-09-14 | City of Hope | Verfahren und kits zur synthese von sirna-expressionskassetten |
EP1578765A4 (de) * | 2002-11-05 | 2008-04-23 | Isis Pharmaceuticals Inc | Oligomere verbindungen,die zuckerersatzstoffe enthalten, und zusammensetzung zur verwendung in dergenmodulation |
US20040248299A1 (en) * | 2002-12-27 | 2004-12-09 | Sumedha Jayasena | RNA interference |
WO2005044976A2 (en) * | 2003-06-20 | 2005-05-19 | Isis Pharmaceuticals, Inc. | Oligomeric compounds for use in gene modulation |
ITRM20030335A1 (it) * | 2003-07-09 | 2005-01-10 | Univ Roma | Sistema di espressione di sirna. |
ES2808561T3 (es) | 2003-09-12 | 2021-03-01 | Univ Massachusetts | Interferencia por ARN para el tratamiento de trastornos de ganancia de función |
US8569474B2 (en) * | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
EP1735009A4 (de) | 2004-03-12 | 2011-03-30 | Alnylam Pharmaceuticals Inc | Irna mittel targeting vegf |
EP2471922A1 (de) * | 2004-05-28 | 2012-07-04 | Asuragen, Inc. | Verfahren und Zusammensetzungen mit microRNA |
AU2005252662B2 (en) * | 2004-06-03 | 2011-08-18 | Isis Pharmaceuticals, Inc. | Double strand compositions comprising differentially modified strands for use in gene modulation |
US8394947B2 (en) * | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
US20060040391A1 (en) * | 2004-08-20 | 2006-02-23 | Promega Corporation | RNA interference vectors |
US7884086B2 (en) * | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
WO2006035432A2 (en) * | 2004-09-27 | 2006-04-06 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | Gene silencing for use in dermatology |
EP2322616A1 (de) | 2004-11-12 | 2011-05-18 | Asuragen, Inc. | Verfahren und Zusammensetzungen, die miRNAs und miRNA-inhibitorischen Molekülen verbunden sind |
WO2008073922A2 (en) * | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Functions and targets of let-7 micro rnas |
AU2006305886C1 (en) | 2005-10-28 | 2011-03-17 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of huntingtin gene |
EP1942948A4 (de) | 2005-11-04 | 2010-03-03 | Alnylam Pharmaceuticals Inc | Zusammensetzungen und verfahren zur hemmung der expression des nav1.8-genes |
US20100069461A1 (en) | 2005-11-09 | 2010-03-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of factor v leiden mutant gene |
KR101547579B1 (ko) | 2006-03-31 | 2015-08-27 | 알닐람 파마슈티칼스 인코포레이티드 | Eg5 유전자의 발현을 억제하는 이본쇄 리보핵산 |
WO2007134161A2 (en) | 2006-05-11 | 2007-11-22 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the pcsk9 gene |
CN101489566B (zh) | 2006-05-19 | 2012-04-18 | 阿尔尼拉姆医药品有限公司 | Aha基因的RNAi调控及其治疗性应用 |
CA2653451C (en) | 2006-05-22 | 2015-12-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of ikk-b gene |
US8598333B2 (en) | 2006-05-26 | 2013-12-03 | Alnylam Pharmaceuticals, Inc. | SiRNA silencing of genes expressed in cancer |
EP2069380B1 (de) | 2006-09-18 | 2014-11-12 | Alnylam Pharmaceuticals Inc. | Rnai-modulation von scap und ihre therapeutische verwendung |
WO2008036776A2 (en) * | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir -31,mir -145, mir-147, mir-188, mir-215, mir-216 mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
JP2010504350A (ja) * | 2006-09-19 | 2010-02-12 | アシュラジェン インコーポレイテッド | 治療的介入の標的としての、miR−200によって調節される遺伝子および経路 |
CA2663581C (en) | 2006-09-21 | 2016-03-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the hamp gene |
CN101627121A (zh) * | 2006-12-08 | 2010-01-13 | 奥斯瑞根公司 | 作为治疗干预的靶标的miRNA调控基因和路径 |
WO2008073920A2 (en) * | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mir-21 regulated genes and pathways as targets for therapeutic intervention |
PE20090064A1 (es) | 2007-03-26 | 2009-03-02 | Novartis Ag | Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende |
JP5350360B2 (ja) | 2007-03-29 | 2013-11-27 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | エボラ由来の遺伝子の発現を阻害するための組成物および方法 |
US20090232893A1 (en) * | 2007-05-22 | 2009-09-17 | Bader Andreas G | miR-143 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
US20090131354A1 (en) * | 2007-05-22 | 2009-05-21 | Bader Andreas G | miR-126 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
JP2010529966A (ja) * | 2007-06-08 | 2010-09-02 | アシュラジェン インコーポレイテッド | 治療的介入の標的としてmiR−34によって調節される遺伝子および経路 |
BRPI0814189A2 (pt) | 2007-07-05 | 2015-03-03 | Novartis Ag | Ácido ribonucleico de filamento duplo, composição farmacêutica e seus usos, método para inibir a expressão de fosfatidilinositol 4-cinase, vetor e uso de um composto que seletivamente inibe a atividade da fosfatidilinositol 4-cinase. |
US8361714B2 (en) * | 2007-09-14 | 2013-01-29 | Asuragen, Inc. | Micrornas differentially expressed in cervical cancer and uses thereof |
EP2190995A2 (de) * | 2007-09-18 | 2010-06-02 | Intradigm Corporation | Zusammensetzungen mit k-ras-sirna und verwendungsverfahren |
US20100280097A1 (en) * | 2007-09-18 | 2010-11-04 | Intradigm Corporation | Compositions comprising hif-1 alpha sirna and methods of use thereof |
US8071562B2 (en) * | 2007-12-01 | 2011-12-06 | Mirna Therapeutics, Inc. | MiR-124 regulated genes and pathways as targets for therapeutic intervention |
JP5530933B2 (ja) | 2007-12-10 | 2014-06-25 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 第vii因子遺伝子発現阻害のための組成物及び方法 |
US20090192114A1 (en) * | 2007-12-21 | 2009-07-30 | Dmitriy Ovcharenko | miR-10 Regulated Genes and Pathways as Targets for Therapeutic Intervention |
US20090263803A1 (en) * | 2008-02-08 | 2009-10-22 | Sylvie Beaudenon | Mirnas differentially expressed in lymph nodes from cancer patients |
JP2011518117A (ja) | 2008-03-05 | 2011-06-23 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Eg5およびVEGF遺伝子の発現を阻害するための組成物および方法 |
US20090233297A1 (en) * | 2008-03-06 | 2009-09-17 | Elizabeth Mambo | Microrna markers for recurrence of colorectal cancer |
CA2717496A1 (en) * | 2008-03-12 | 2009-09-17 | Intradigm Corporation | Compositions comprising notch1 sirna and methods of use thereof |
EP2271757A2 (de) * | 2008-03-26 | 2011-01-12 | Asuragen, INC. | Zusammensetzungen und verfahren in zusammenhang mit mir-16 und prostatakrebstherapie |
WO2009126726A1 (en) * | 2008-04-08 | 2009-10-15 | Asuragen, Inc | Methods and compositions for diagnosing and modulating human papillomavirus (hpv) |
WO2009126727A1 (en) * | 2008-04-10 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Rna compositions for modulating immune response |
US8258111B2 (en) * | 2008-05-08 | 2012-09-04 | The Johns Hopkins University | Compositions and methods related to miRNA modulation of neovascularization or angiogenesis |
WO2009147684A2 (en) * | 2008-06-06 | 2009-12-10 | Quark Pharmaceuticals, Inc. | Compositions and methods for treatment of ear disorders |
US9433684B2 (en) | 2008-08-19 | 2016-09-06 | Nektar Therapeutics | Conjugates of small-interfering nucleic acids |
WO2010028054A1 (en) | 2008-09-02 | 2010-03-11 | Alnylam Europe Ag. | Compositions and methods for inhibiting expression of mutant egfr gene |
EP2334793B1 (de) | 2008-09-25 | 2016-04-06 | Alnylam Pharmaceuticals, Inc. | Zusammensetzungen und verfahren zur hemmung der expression des serumamyloid-a-gens |
EA029762B1 (ru) | 2008-10-20 | 2018-05-31 | Элнилэм Фармасьютикалз, Инк. | Композиции и способы для ингибирования экспрессии транстиретина |
US20100179213A1 (en) * | 2008-11-11 | 2010-07-15 | Mirna Therapeutics, Inc. | Methods and Compositions Involving miRNAs In Cancer Stem Cells |
WO2010068816A1 (en) | 2008-12-10 | 2010-06-17 | Alnylam Pharmaceuticals, Inc. | Gnaq targeted dsrna compositions and methods for inhibiting expression |
WO2010099341A1 (en) | 2009-02-26 | 2010-09-02 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of mig-12 gene |
JP6032724B2 (ja) | 2009-03-12 | 2016-11-30 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | 脂質製剤組成物およびEg5遺伝子とVEGF遺伝子の発現を阻害する方法 |
CN102575252B (zh) | 2009-06-01 | 2016-04-20 | 光环生物干扰疗法公司 | 用于多价rna干扰的多核苷酸、组合物及其使用方法 |
WO2010147992A1 (en) | 2009-06-15 | 2010-12-23 | Alnylam Pharmaceuticals, Inc. | Methods for increasing efficacy of lipid formulated sirna |
CN104651408A (zh) | 2009-06-15 | 2015-05-27 | 阿尔尼拉姆医药品有限公司 | 靶向pcsk9基因的脂质配制的dsrna |
AP2015008874A0 (en) | 2009-08-14 | 2015-11-30 | Alnylam Pharmaceuticals Inc | Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus |
WO2011035065A1 (en) | 2009-09-17 | 2011-03-24 | Nektar Therapeutics | Monoconjugated chitosans as delivery agents for small interfering nucleic acids |
AU2011235276B2 (en) | 2010-03-29 | 2015-09-03 | Alnylam Pharmaceuticals, Inc. | SiRNA therapy for transthyretin (TTR) related ocular amyloidosis |
EP2576579B1 (de) | 2010-06-02 | 2018-08-08 | Alnylam Pharmaceuticals, Inc. | Zusammensetzungen und verfahren zur behandlung von leberfibrose |
AR083445A1 (es) | 2010-10-14 | 2013-02-27 | Univ Mie | siARN CONTRA LA FIBROSIS |
CN110123830A (zh) | 2010-11-09 | 2019-08-16 | 阿尔尼拉姆医药品有限公司 | 用于抑制Eg5和VEGF基因的表达的脂质配制的组合物和方法 |
CA2839896A1 (en) | 2011-06-21 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Assays and methods for determining activity of a therapeutic agent in a subject |
US9228188B2 (en) | 2011-06-21 | 2016-01-05 | Alnylam Pharmaceuticals, Inc. | Compositions and method for inhibiting hepcidin antimicrobial peptide (HAMP) or HAMP-related gene expression |
RU2631805C2 (ru) | 2011-06-21 | 2017-09-26 | Элнилэм Фармасьютикалз, Инк. | Композиции и способы ингибирования экспрессии генов аполипопротеина с-iii (арос3) |
EP3366312A1 (de) | 2011-06-23 | 2018-08-29 | Alnylam Pharmaceuticals, Inc. | Serpina 1 sirnas: materialzusammensetzungen und verfahren zur behandlung |
US9644241B2 (en) | 2011-09-13 | 2017-05-09 | Interpace Diagnostics, Llc | Methods and compositions involving miR-135B for distinguishing pancreatic cancer from benign pancreatic disease |
AU2014243796B2 (en) | 2013-03-13 | 2018-07-19 | GeneWeave Biosciences, Inc. | Non-replicative transduction particles and transduction particle-based reporter systems |
BR112015026702A2 (pt) | 2013-04-21 | 2018-02-06 | Yeda Res And Developmente Co Ltd | métodos de extermínio de células senescentes |
US20180345047A1 (en) | 2015-02-26 | 2018-12-06 | Yeda Research And Development Co. Ltd. | Method of promoting hair growth |
AU2016312530A1 (en) | 2015-08-24 | 2018-03-01 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotide nanoparticles for the modulation of gene expression and uses thereof |
AU2016310494B2 (en) | 2015-08-25 | 2022-06-09 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a proprotein convertase subtilisin kexin (PCSK9) gene-associated disorder |
MA45469A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques de bêta-caténine et leurs utilisations |
MA45328A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Compositions acide nucléique-polypeptide et utilisations de celles-ci |
MA45470A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques kras et leurs utilisations |
MA45349A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques egfr et leurs utilisations |
EP3720448A4 (de) | 2017-12-06 | 2021-11-03 | Avidity Biosciences, Inc. | Zusammensetzungen und verfahren zur behandlung von muskelatrophie und myotonischer dystrophie |
CN115666589A (zh) | 2020-03-19 | 2023-01-31 | 艾维迪提生物科学公司 | 治疗面肩肱型肌营养不良的组合物和方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994001550A1 (en) * | 1992-07-02 | 1994-01-20 | Hybridon, Inc. | Self-stabilized oligonucleotides as therapeutic agents |
WO1998005770A2 (de) * | 1996-08-07 | 1998-02-12 | Deutches Krebsforschungszentrum Stiftung Des Öffentlichen Rechts | Anti-sinn-rna mit sekundärstruktur |
WO1999032619A1 (en) * | 1997-12-23 | 1999-07-01 | The Carnegie Institution Of Washington | Genetic inhibition by double-stranded rna |
WO2000044895A1 (de) * | 1999-01-30 | 2000-08-03 | Roland Kreutzer | Verfahren und medikament zur hemmung der expression eines vorgegebenen gens |
WO2000044914A1 (en) * | 1999-01-28 | 2000-08-03 | Medical College Of Georgia Research Institute, Inc. | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna |
Family Cites Families (81)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5208149A (en) * | 1983-10-20 | 1993-05-04 | The Research Foundation Of State University Of New York | Nucleic acid constructs containing stable stem and loop structures |
US5190931A (en) * | 1983-10-20 | 1993-03-02 | The Research Foundation Of State University Of New York | Regulation of gene expression by employing translational inhibition of MRNA utilizing interfering complementary MRNA |
US4980286A (en) * | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
AU6131086A (en) * | 1985-07-05 | 1987-01-30 | Whitehead Institute For Biomedical Research | Epithelial cells expressing foreign genetic material |
US5107065A (en) * | 1986-03-28 | 1992-04-21 | Calgene, Inc. | Anti-sense regulation of gene expression in plant cells |
US4987071A (en) * | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
US5712257A (en) * | 1987-08-12 | 1998-01-27 | Hem Research, Inc. | Topically active compositions of mismatched dsRNAs |
EP0633318A1 (de) | 1987-09-11 | 1995-01-11 | Whitehead Institute For Biomedical Research | Transduktionsveränderte Fibroblasten und ihre Anwendung |
ATE110108T1 (de) | 1987-12-11 | 1994-09-15 | Whitehead Biomedical Inst | Genetische modifizierung von endothelialen zellen. |
US5254678A (en) * | 1987-12-15 | 1993-10-19 | Gene Shears Pty. Limited | Ribozymes |
ATE152169T1 (de) | 1988-02-05 | 1997-05-15 | Whitehead Biomedical Inst | Modifizierte hepatozyten und deren anwendung |
US5328470A (en) * | 1989-03-31 | 1994-07-12 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
US5212295A (en) * | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
US5587361A (en) * | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
EP0568537B1 (de) | 1990-10-31 | 1998-02-04 | Somatix Therapy Corporation | Genetische veränderung von endothelzellen |
FR2675803B1 (fr) | 1991-04-25 | 1996-09-06 | Genset Sa | Oligonucleotides fermes, antisens et sens et leurs applications. |
EP0635023B1 (de) * | 1992-03-05 | 2002-02-06 | Isis Pharmaceuticals, Inc. | Kovalent vernetzte oligonukleotide |
US6423489B1 (en) * | 1992-09-10 | 2002-07-23 | Isis Pharmaceuticals, Inc. | Compositions and methods for treatment of Hepatitis C virus-associated diseases |
US6054299A (en) * | 1994-04-29 | 2000-04-25 | Conrad; Charles A. | Stem-loop cloning vector and method |
US6166197A (en) * | 1995-03-06 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions |
US5674683A (en) * | 1995-03-21 | 1997-10-07 | Research Corporation Technologies, Inc. | Stem-loop and circular oligonucleotides and method of using |
US5998203A (en) * | 1996-04-16 | 1999-12-07 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids containing 5'-and/or 3'-cap structures |
US6127533A (en) * | 1997-02-14 | 2000-10-03 | Isis Pharmaceuticals, Inc. | 2'-O-aminooxy-modified oligonucleotides |
GB9710475D0 (en) | 1997-05-21 | 1997-07-16 | Zeneca Ltd | Gene silencing |
GB9720148D0 (en) | 1997-09-22 | 1997-11-26 | Innes John Centre Innov Ltd | Gene silencing materials and methods |
EP1071762A4 (de) | 1998-03-20 | 2003-09-24 | Benitec Australia Ltd | Kontrolle der genexpression |
EP1068311B2 (de) | 1998-04-08 | 2020-12-09 | Commonwealth Scientific and Industrial Research Organisation | Verfahren und mittel zum erhalt von veränderten phänotypen |
AR020078A1 (es) | 1998-05-26 | 2002-04-10 | Syngenta Participations Ag | Metodo para alterar la expresion de un gen objetivo en una celula de planta |
GB9827152D0 (en) | 1998-07-03 | 1999-02-03 | Devgen Nv | Characterisation of gene function using double stranded rna inhibition |
US6271358B1 (en) * | 1998-07-27 | 2001-08-07 | Isis Pharmaceuticals, Inc. | RNA targeted 2′-modified oligonucleotides that are conformationally preorganized |
US6486299B1 (en) * | 1998-09-28 | 2002-11-26 | Curagen Corporation | Genes and proteins predictive and therapeutic for stroke, hypertension, diabetes and obesity |
AU6430599A (en) | 1998-10-09 | 2000-05-01 | Cytogenix, Inc. | Enzymatic synthesis of ssdna |
BR9914773A (pt) | 1998-10-09 | 2002-02-05 | Ingene Inc | Conjunto de elementos genéricos, método para a produção de dna de cordão único, transcrição de mrna, construção de ácido nucléico, transcrição de ssdna, vetor, sistema vetor, célula hospedeira, conjunto para a produção de uma sequência de ácido nucléico de cordão único, método para a produção in vivo ou in vitro de uma sequência de ácido nucléico de cordão único, transcrição de cdna de cordão único, ácido nucléico inibidor, molécula heteroduplex, e composição farmacêutica |
US6200924B1 (en) | 1999-01-29 | 2001-03-13 | E. I. Du Pont De Nemours And Company | Porous highly fluorinated acidic polymer catalyst |
JP2002542263A (ja) | 1999-04-21 | 2002-12-10 | ワイス | ポリヌクレオチド配列の機能を阻害するための方法および組成物 |
EP1801215B1 (de) | 1999-05-10 | 2013-02-27 | Syngenta Participations AG | Regulierung der viralen Genexpression |
US6569623B1 (en) | 1999-09-08 | 2003-05-27 | Ramot University Authority For Applied Research & Industrial Development Ltd. | Genetic screening methods |
US6861220B2 (en) * | 1999-09-08 | 2005-03-01 | Ramot University Authority For Applied Research & Industrial Development Ltd | Genetic screening methods |
EP1235842A4 (de) | 1999-10-15 | 2003-04-23 | Univ Massachusetts | Gene des rns-interferenzweges als hilfsmittel der gezielten gentischen interferenz |
GB9927444D0 (en) * | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
DE10100586C1 (de) | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
RU2164944C1 (ru) | 1999-12-09 | 2001-04-10 | Институт молекулярной биологии им. В.А. Энгельгардта РАН | Способ изменения генетических свойств организма |
GB9930691D0 (en) | 1999-12-24 | 2000-02-16 | Devgen Nv | Improvements relating to double-stranded RNA inhibition |
US20070026394A1 (en) * | 2000-02-11 | 2007-02-01 | Lawrence Blatt | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies |
IL151781A0 (en) | 2000-03-16 | 2003-04-10 | Genetica Inc | Methods and compositions for rna interference |
CA2403162A1 (en) | 2000-03-17 | 2001-09-27 | Benitec Australia Ltd. | Genetic silencing |
EP2345742B1 (de) * | 2000-03-30 | 2014-06-11 | The Whitehead Institute for Biomedical Research | Mediatoren von RNS-interferenz, die RNS-sequenzspezifisch sind |
WO2001092513A1 (en) | 2000-05-30 | 2001-12-06 | Johnson & Johnson Research Pty Limited | METHODS FOR MEDIATING GENE SUPPRESION BY USING FACTORS THAT ENHANCE RNAi |
EP1309706A2 (de) | 2000-08-19 | 2003-05-14 | Axordia Limited | Modulation der stammzell-differenzierung |
US20030190635A1 (en) * | 2002-02-20 | 2003-10-09 | Mcswiggen James A. | RNA interference mediated treatment of Alzheimer's disease using short interfering RNA |
AU2001296333A1 (en) | 2000-09-26 | 2002-04-08 | The Burnham Institute | Paad domain-containing polypeptides, encoding nucleic acids, and methods of use |
WO2002068637A2 (en) | 2000-10-20 | 2002-09-06 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid-based treatment of diseases or conditions related to west nile virus infection |
US20020173478A1 (en) * | 2000-11-14 | 2002-11-21 | The Trustees Of The University Of Pennsylvania | Post-transcriptional gene silencing by RNAi in mammalian cells |
CZ308053B6 (cs) | 2000-12-01 | 2019-11-27 | Max Planck Gesellschaft | Izolovaná molekula dvouřetězcové RNA, způsob její výroby a její použití |
WO2002061034A2 (en) | 2000-12-08 | 2002-08-08 | Invitrogen Corporation | Compositions and methods for rapidly generating recombinant nucleic acid molecules |
WO2003035869A1 (de) | 2001-10-26 | 2003-05-01 | Ribopharma Ag | Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens |
WO2002072601A2 (en) * | 2001-02-07 | 2002-09-19 | The Burnham Institute | Apoptosis modulator bcl-b and methods for making and using same |
GB0104948D0 (en) | 2001-02-28 | 2001-04-18 | Novartis Res Foundation | Novel methods |
US20020132346A1 (en) * | 2001-03-08 | 2002-09-19 | Jose Cibelli | Use of RNA interference for the creation of lineage specific ES and other undifferentiated cells and production of differentiated cells in vitro by co-culture |
WO2003070750A2 (en) | 2002-02-20 | 2003-08-28 | Sirna Therapeutics, Inc | Rna interference mediated inhibition of hepatitis c virus |
EP2345720A3 (de) | 2001-07-12 | 2012-01-25 | University of Massachusetts | In-vivo-Herstellung kleiner interferierender und Genverstummung vermittelnder RNAs |
GB0118223D0 (en) | 2001-07-26 | 2001-09-19 | Univ Sheffield | Stem loop RNA |
WO2003012052A2 (en) | 2001-07-30 | 2003-02-13 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Specific inhibition of gene expression by small double stranded rnas |
WO2003016572A1 (en) | 2001-08-17 | 2003-02-27 | Eli Lilly And Company | Oligonucleotide therapeutics for treating hepatitis c virus infections |
US7101995B2 (en) * | 2001-08-27 | 2006-09-05 | Mirus Bio Corporation | Compositions and processes using siRNA, amphipathic compounds and polycations |
US20030198627A1 (en) * | 2001-09-01 | 2003-10-23 | Gert-Jan Arts | siRNA knockout assay method and constructs |
DE10163098B4 (de) | 2001-10-12 | 2005-06-02 | Alnylam Europe Ag | Verfahren zur Hemmung der Replikation von Viren |
DE10230996A1 (de) | 2001-10-26 | 2003-07-17 | Ribopharma Ag | Medikament zur Behandlung eines Pankreaskarzinoms |
WO2003035870A1 (de) | 2001-10-26 | 2003-05-01 | Ribopharma Ag | Medikament zur behandlung eines pankreaskarzinoms |
CN1604783A (zh) | 2001-10-26 | 2005-04-06 | 里伯药品公司 | 通过rna干扰治疗纤维化疾病的药物 |
CN1608133A (zh) | 2001-10-26 | 2005-04-20 | 里伯药品公司 | 双链核糖核酸用于治疗正(+)链rna病毒感染的用途 |
AU2002368202B2 (en) * | 2001-11-02 | 2008-06-05 | Insert Therapeutics, Inc | Methods and compositions for therapeutic use of RNA interference |
FR2832154B1 (fr) * | 2001-11-09 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
AU2002356898A1 (en) * | 2001-11-15 | 2003-06-10 | Tularik Inc. | Gene amplification and overexpression in cancer |
AU2003219833A1 (en) | 2002-02-20 | 2003-09-09 | Sirna Therapeutics Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
AU2003207708A1 (en) | 2002-02-20 | 2003-09-09 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of map kinase genes |
JP2005517452A (ja) | 2002-02-20 | 2005-06-16 | サーナ・セラピューティクス・インコーポレイテッド | 短干渉核酸(siNA)を用いるBCL2遺伝子発現のRNA干渉媒介性阻害 |
AU2003206946A1 (en) | 2002-02-22 | 2003-09-09 | Klaus Strebhardt | Agent for inhibiting development or progress of proliferative diseases and especially cancer diseases and pharmaceutical composition containing said agent |
US20030180756A1 (en) * | 2002-03-21 | 2003-09-25 | Yang Shi | Compositions and methods for suppressing eukaryotic gene expression |
NZ556097A (en) * | 2005-01-07 | 2009-12-24 | Alnylam Pharmaceuticals Inc | Rnai modulation of RSV and therapeutic uses thereof |
-
2001
- 2001-01-09 DE DE10100586A patent/DE10100586C1/de not_active Expired - Lifetime
-
2002
- 2002-01-09 CN CNA028035550A patent/CN1650010A/zh active Pending
- 2002-01-09 ES ES02702247T patent/ES2204360T3/es not_active Expired - Lifetime
- 2002-01-09 AT AT02702247T patent/ATE460481T1/de active
- 2002-01-09 EP EP10002422.3A patent/EP2213736B1/de not_active Expired - Lifetime
- 2002-01-09 EP EP02702247A patent/EP1349927B1/de not_active Revoked
- 2002-01-09 JP JP2002556739A patent/JP4209678B2/ja not_active Expired - Lifetime
- 2002-01-09 EP EP10011812A patent/EP2365075A1/de not_active Withdrawn
- 2002-01-09 DE DE50214266T patent/DE50214266D1/de not_active Expired - Lifetime
- 2002-01-09 WO PCT/EP2002/000151 patent/WO2002055692A2/de active Application Filing
- 2002-01-09 CA CA002432341A patent/CA2432341A1/en not_active Abandoned
-
2003
- 2003-03-07 US US10/384,260 patent/US7473525B2/en not_active Expired - Lifetime
- 2003-05-28 ZA ZA200304127A patent/ZA200304127B/en unknown
- 2003-06-10 ZA ZA200304500A patent/ZA200304500B/xx unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994001550A1 (en) * | 1992-07-02 | 1994-01-20 | Hybridon, Inc. | Self-stabilized oligonucleotides as therapeutic agents |
WO1998005770A2 (de) * | 1996-08-07 | 1998-02-12 | Deutches Krebsforschungszentrum Stiftung Des Öffentlichen Rechts | Anti-sinn-rna mit sekundärstruktur |
WO1999032619A1 (en) * | 1997-12-23 | 1999-07-01 | The Carnegie Institution Of Washington | Genetic inhibition by double-stranded rna |
WO2000044914A1 (en) * | 1999-01-28 | 2000-08-03 | Medical College Of Georgia Research Institute, Inc. | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna |
WO2000044895A1 (de) * | 1999-01-30 | 2000-08-03 | Roland Kreutzer | Verfahren und medikament zur hemmung der expression eines vorgegebenen gens |
Non-Patent Citations (5)
Title |
---|
AMBROS VICTOR: "Dicing up RNAs" SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, US, Bd. 293, Nr. 5531, 3. August 2001 (2001-08-03), Seiten 811-813, XP002183122 ISSN: 0036-8075 * |
BASS BRENDA L: "Double-stranded RNA as a template for gene silencing" CELL, CELL PRESS, CAMBRIDGE, NA, US, Bd. 101, Nr. 3, 28. April 2000 (2000-04-28), Seiten 235-238, XP002194756 ISSN: 0092-8674 * |
GAUTSCHI O., TSCHOPP S., OLIE R.A. ET AL: "Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins." J. NATL. CANCER INST., Bd. 93, Nr. 6, 21. März 2001 (2001-03-21), Seiten 463-471, XP009003270 in der Anmeldung erwähnt * |
See also references of EP1349927A2 * |
ZAMORE PHILLIP D ET AL: "RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals" CELL, CELL PRESS, CAMBRIDGE, NA, US, Bd. 101, Nr. 1, 31. März 2000 (2000-03-31), Seiten 25-33, XP002208683 ISSN: 0092-8674 * |
Cited By (181)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8101742B2 (en) | 1999-01-30 | 2012-01-24 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8183362B2 (en) | 1999-01-30 | 2012-05-22 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US9902955B2 (en) | 1999-01-30 | 2018-02-27 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8729037B2 (en) | 1999-01-30 | 2014-05-20 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8114981B2 (en) | 1999-01-30 | 2012-02-14 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8114851B2 (en) | 1999-01-30 | 2012-02-14 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US9133454B2 (en) | 1999-01-30 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8202980B2 (en) | 1999-01-30 | 2012-06-19 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8119608B2 (en) | 1999-01-30 | 2012-02-21 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8168776B2 (en) | 1999-01-30 | 2012-05-01 | Alnylam Pharmaceuticals, Inc. | Method for making a 21 nucleotide double stranded RNA chemically linked at one end |
US8101584B2 (en) | 1999-01-30 | 2012-01-24 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a given gene |
US8367630B2 (en) | 1999-03-17 | 2013-02-05 | The University Of North Carolina At Chapel Hill | Method for inhibiting expression of a protein in a hepatocyte |
US7829693B2 (en) | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
US8394628B2 (en) | 2000-03-30 | 2013-03-12 | University Of Massachusetts | RNA sequence-specific mediators of RNA interference |
US9193753B2 (en) | 2000-03-30 | 2015-11-24 | University Of Massachusetts | RNA sequence-specific mediators of RNA interference |
US9012138B2 (en) | 2000-03-30 | 2015-04-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA sequence-specific mediators of RNA interference |
US9012621B2 (en) | 2000-03-30 | 2015-04-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA sequence-specific mediators of RNA interference |
US8632997B2 (en) | 2000-03-30 | 2014-01-21 | University Of Massachusetts | RNA sequence-specific mediators of RNA interference |
US8790922B2 (en) | 2000-03-30 | 2014-07-29 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA sequence-specific mediators of RNA interference |
US8742092B2 (en) | 2000-03-30 | 2014-06-03 | University Of Massachusetts | RNA sequence-specific mediators of RNA interference |
US8420391B2 (en) | 2000-03-30 | 2013-04-16 | University Of Massachusetts | RNA sequence-specific mediators of RNA interference |
US10472625B2 (en) | 2000-03-30 | 2019-11-12 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA sequence-specific mediators of RNA interference |
US8552171B2 (en) | 2000-03-30 | 2013-10-08 | University Of Massachusetts | RNA sequence-specific mediators of RNA interference |
US8993745B2 (en) | 2000-12-01 | 2015-03-31 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8895721B2 (en) | 2000-12-01 | 2014-11-25 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8445237B2 (en) | 2000-12-01 | 2013-05-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8895718B2 (en) | 2000-12-01 | 2014-11-25 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8778902B2 (en) | 2000-12-01 | 2014-07-15 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8372968B2 (en) | 2000-12-01 | 2013-02-12 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8796016B2 (en) | 2000-12-01 | 2014-08-05 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8853384B2 (en) | 2000-12-01 | 2014-10-07 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8765930B2 (en) | 2000-12-01 | 2014-07-01 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US8362231B2 (en) | 2000-12-01 | 2013-01-29 | Max-Planck-Gesellschaft zur Föderung der Wissenschaften E.V. | RNA interference mediating small RNA molecules |
US10633656B2 (en) | 2000-12-01 | 2020-04-28 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | RNA interference mediating small RNA molecules |
US8933044B2 (en) | 2000-12-01 | 2015-01-13 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US7056704B2 (en) | 2000-12-01 | 2006-06-06 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. | RNA interference mediating small RNA molecules |
US7078196B2 (en) | 2000-12-01 | 2006-07-18 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften, E.V. | RNA interference mediating small RNA molecules |
US8329463B2 (en) | 2000-12-01 | 2012-12-11 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA interference mediating small RNA molecules |
US9587240B2 (en) | 2001-01-09 | 2017-03-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
US7473525B2 (en) | 2001-01-09 | 2009-01-06 | Alnylam Europe Ag | Compositions and methods for inhibiting expression of anti-apoptotic genes |
EP2264173A3 (de) * | 2001-01-09 | 2015-01-14 | Alnylam Europe AG | Verwendung einer doppelsträngigen Ribonukleinsäure zur gezielten Hemmung der Expression eines vorgegebenen Zielgens |
US7767802B2 (en) | 2001-01-09 | 2010-08-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US9074213B2 (en) | 2001-01-09 | 2015-07-07 | Alnylam Pharmacuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
US8530438B2 (en) | 2001-07-12 | 2013-09-10 | University Of Massachusetts | Vivo production of small interfering RNAs that mediate gene silencing |
US8232260B2 (en) | 2001-07-12 | 2012-07-31 | University Of Massachusetts | In vivo production of small interfering RNAs that mediate gene silencing |
US9850487B2 (en) | 2001-07-12 | 2017-12-26 | University Of Massachusetts | In vivo production of small interfering RNAs that mediate gene silencing |
US8557785B2 (en) | 2001-07-12 | 2013-10-15 | University Of Massachusetts | In vivo production of small interfering RNAS that mediate gene silencing |
US7691995B2 (en) | 2001-07-12 | 2010-04-06 | University Of Massachusetts | In vivo production of small interfering RNAS that mediate gene silencing |
US7893036B2 (en) | 2001-07-12 | 2011-02-22 | University Of Massachusetts | In vivo production of small interfering RNAs that mediate gene silencing |
US9175287B2 (en) | 2001-07-12 | 2015-11-03 | University Of Massachusetts | In vivo production of small interfering RNAs that mediate gene silencing |
US10731155B2 (en) | 2001-07-12 | 2020-08-04 | University Of Massachusetts | In vivo production of small interfering RNAs that mediate gene silencing |
US7763590B2 (en) | 2001-10-12 | 2010-07-27 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a mutant gene |
US7745418B2 (en) | 2001-10-12 | 2010-06-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting viral replication |
US7348314B2 (en) | 2001-10-12 | 2008-03-25 | Alnylam Europe Ag | Compositions and methods for inhibiting viral replication |
WO2003035869A1 (de) * | 2001-10-26 | 2003-05-01 | Ribopharma Ag | Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens |
WO2003040366A3 (fr) * | 2001-11-09 | 2004-07-01 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
US7371735B2 (en) | 2001-11-09 | 2008-05-13 | Centre National De La Recherche Scientifique-Cnrs | Inhibitor oligonucleotides and their use for specific repression of a gene |
WO2003040366A2 (fr) * | 2001-11-09 | 2003-05-15 | Centre National De La Recherche Scientifique -Cnrs- | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
US8318689B2 (en) | 2001-11-09 | 2012-11-27 | Centre National De La Recherche Scientifique | SiRNA-based cancer treatment |
US7615341B2 (en) | 2002-01-11 | 2009-11-10 | Shunichi Shiozawa | Disease susceptibility gene for rheumatoid arthritis, protein thereof, evaluation method and evaluation kit for evaluating onset possibility of rheumatoid arthritis by using those, and remedy and curing medicine for rheumatoid arthritis |
WO2003060126A1 (fr) * | 2002-01-11 | 2003-07-24 | Shunichi Shiozawa | Gene sensible a la polyarthrite rhumatoide, sa proteine, procede et kit permettant d'evaluer l'apparition de la maladie a travers ce gene, ainsi que procede et medicaments pour le traitement de ladite maladie |
US7846907B2 (en) | 2002-01-22 | 2010-12-07 | Alnylam Pharmaceuticals, Inc. | Double-stranded RNA (dsRNA) and method of use for inhibiting expression of a fusion gene |
US7196184B2 (en) | 2002-01-22 | 2007-03-27 | Alnylam Europe Ag | Double-stranded RNA (DSRNA) and method of use for inhibiting expression of the AML-1/MTG8 fusion gene |
US10626398B2 (en) | 2002-02-01 | 2020-04-21 | Life Technologies Corporation | Oligonucleotide compositions with enhanced efficiency |
US9657294B2 (en) | 2002-02-20 | 2017-05-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US9732344B2 (en) | 2002-02-20 | 2017-08-15 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
WO2003070918A2 (en) | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | Rna interference by modified short interfering nucleic acid |
EP1442143A2 (de) * | 2002-02-20 | 2004-08-04 | Sirna Therapeutics, Inc. | DURCH RNA-INTERFERENZ VERMITTELTE HEMMUNG DER BCL2-GENEXPRESSION UNTER VERWENDUNG VON siNA (SHORT INTERFERING NUCLEIC ACID) |
EP3926046A2 (de) | 2002-02-20 | 2021-12-22 | Sirna Therapeutics, Inc. | Durch rna-interferenz vermittelte inhibition der genexpression unter verwendung von kurzer interferierender nukleinsäure (sina) |
EP2902406A1 (de) | 2002-02-20 | 2015-08-05 | Sirna Therapeutics, Inc. | RNA-Interferenz-vermittelte Inhibition von Genexpression unter Verwendung kurzer interferierender Nukleinsäure (siNA) |
EP2287305A1 (de) | 2002-02-20 | 2011-02-23 | Sirna Therapeutics, Inc. | RNA-Interferenz-vermittelte Inhibition von Genexpression unter Verwendung kurzer interferierender Nukleinsäure (siNA) |
EP2287306A1 (de) | 2002-02-20 | 2011-02-23 | Sirna Therapeutics, Inc. | RNA-Interferenz-vermittelte Inhibition von Genexpression unter Verwendung kurzer interferierender Nukleinsäure (siNA) |
EP1442143A4 (de) * | 2002-02-20 | 2005-02-16 | Sirna Therapeutics Inc | DURCH RNA-INTERFERENZ VERMITTELTE HEMMUNG DER BCL2-GENEXPRESSION UNTER VERWENDUNG VON siNA (SHORT INTERFERING NUCLEIC ACID) |
EP2278004A1 (de) | 2002-02-20 | 2011-01-26 | Sirna Therapeutics, Inc. | RNA-Interferenz-vermittelte Inhibition von Genexpression unter Verwendung kurzer interferierender Nukleinsäure (siNA) |
WO2005028649A1 (en) | 2002-02-20 | 2005-03-31 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US10351852B2 (en) | 2002-02-20 | 2019-07-16 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US9738899B2 (en) | 2002-02-20 | 2017-08-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US10889815B2 (en) | 2002-02-20 | 2021-01-12 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US9771588B2 (en) | 2002-02-20 | 2017-09-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US9957517B2 (en) | 2002-02-20 | 2018-05-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US10000754B2 (en) | 2002-02-20 | 2018-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
EP2042510A2 (de) | 2002-02-20 | 2009-04-01 | Sirna Therapeutics Inc. | RNA-Interferenz-vermittelte Inhibition von Genexpression unter Verwendung chemisch modifizierter kurzer interferierender Nukleinsäure (siNA) |
EP3354656A1 (de) | 2002-02-20 | 2018-08-01 | Sirna Therapeutics, Inc. | Rna-interferenz-vermittelte inhibition von genexpression unter verwendung kurzer interferierender nukleinsäure (sina) |
US10662428B2 (en) | 2002-02-20 | 2020-05-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
EP3459963A1 (de) | 2002-02-20 | 2019-03-27 | Sirna Therapeutics, Inc. | Rna-interferenz-vermittelte inhibition von genexpression unter verwendung kurzer interferierender nukleinsäure (sina) |
US7399586B2 (en) | 2002-05-23 | 2008-07-15 | Ceptyr, Inc. | Modulation of biological signal transduction by RNA interference |
US8541384B2 (en) | 2002-07-24 | 2013-09-24 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of angiogenesis |
US9150863B2 (en) | 2002-07-24 | 2015-10-06 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of angiogenesis |
US8946403B2 (en) | 2002-07-24 | 2015-02-03 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of angiogenesis |
US8546345B2 (en) | 2002-07-24 | 2013-10-01 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of angiogenesis |
US8779116B2 (en) | 2002-08-05 | 2014-07-15 | University Of Iowa Research Foundation | SiRNA-mediated gene silencing |
US9487779B2 (en) | 2002-08-05 | 2016-11-08 | University Of Iowa Research Foundation | siRNA-mediated gene silencing |
US8524879B2 (en) | 2002-08-05 | 2013-09-03 | University Of Iowa Research Foundation | RNA interference suppresion of neurodegenerative diseases and methods of use thereof |
US10072264B2 (en) | 2002-08-05 | 2018-09-11 | University Of Iowa Research Foundation | RNA interference suppression of neurodegenerative diseases and methods of use |
US8481710B2 (en) | 2002-08-05 | 2013-07-09 | University Of Iowa Research Foundation | RNA interference suppression of neurodegenerative diseases and methods of use thereof |
US9260716B2 (en) | 2002-08-05 | 2016-02-16 | University Of Iowa Research Foundation | RNA interference suppression of neurodegenerative diseases and methods of use thereof |
US8329890B2 (en) | 2002-08-05 | 2012-12-11 | University Of Iowa Research Foundation | SiRNA-mediated gene silencing |
US9611472B2 (en) | 2002-08-07 | 2017-04-04 | University Of Massachusetts | Compositions for RNA interference and methods of use thereof |
US8729036B2 (en) | 2002-08-07 | 2014-05-20 | University Of Massachusetts | Compositions for RNA interference and methods of use thereof |
US7892793B2 (en) | 2002-11-04 | 2011-02-22 | University Of Massachusetts | Allele-specific RNA interference |
JP2004173512A (ja) * | 2002-11-22 | 2004-06-24 | Takashi Morita | RNAiによる新規治療法および治療剤 |
WO2004083240A2 (en) * | 2003-03-18 | 2004-09-30 | Jo Milner | Regulation of gene expression |
WO2004083240A3 (en) * | 2003-03-18 | 2005-03-24 | Jo Milner | Regulation of gene expression |
JP2006522806A (ja) * | 2003-03-26 | 2006-10-05 | マルチセル・イミュノセラピューティクス,インコーポレイテッド | 細胞死及び/又はアポトーシスを誘導するための、選択されたrnaモチーフ |
EP2251039A3 (de) * | 2003-05-30 | 2010-12-08 | Nippon Shinyaku Co., Ltd. | Doppelsträngige Oligo-RNA zum Hemmen der Expression von BCL-2 und sie enthaltende pharmazeutische Zusammensetzung |
EP1640452A1 (de) * | 2003-05-30 | 2006-03-29 | Nippon Shinyaku Co., Ltd. | Die expression von bcl-2 hemmende doppelstrang-oligo-rna und diese enthaltende pharmazeutische zusammensetzung |
EP2251039A2 (de) | 2003-05-30 | 2010-11-17 | Nippon Shinyaku Co., Ltd. | Doppelsträngige Oligo-RNA zum Hemmen der Expression von BCL-2 und sie enthaltende pharmazeutische Zusammensetzung |
EP1637144A1 (de) * | 2003-05-30 | 2006-03-22 | Nippon Shinyaku Co., Ltd. | Oligonucleinsäure enthaltender komposit und diesen enthaltende pharmazeutische zusammensetzung |
EP1640452A4 (de) * | 2003-05-30 | 2009-12-23 | Nippon Shinyaku Co Ltd | Die expression von bcl-2 hemmende doppelstrang-oligo-rna und diese enthaltende pharmazeutische zusammensetzung |
EP1637144A4 (de) * | 2003-05-30 | 2010-01-13 | Nippon Shinyaku Co Ltd | Oligonucleinsäure enthaltender komposit und diesen enthaltende pharmazeutische zusammensetzung |
US10604754B2 (en) | 2003-06-02 | 2020-03-31 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
US8304530B2 (en) | 2003-06-02 | 2012-11-06 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
US10364429B2 (en) | 2003-06-02 | 2019-07-30 | University Of Massachusetts | Methods and compositions for controlling efficacy of RNA silencing |
US7750144B2 (en) | 2003-06-02 | 2010-07-06 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
US8329892B2 (en) | 2003-06-02 | 2012-12-11 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
US8309705B2 (en) | 2003-06-02 | 2012-11-13 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
US11459562B2 (en) | 2003-06-02 | 2022-10-04 | University Of Massachusetts | Methods and compositions for controlling efficacy of RNA silencing |
US9121018B2 (en) | 2003-06-02 | 2015-09-01 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
US8309704B2 (en) | 2003-06-02 | 2012-11-13 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNAi |
EP1633770A2 (de) * | 2003-06-13 | 2006-03-15 | Alnylam Europe AG | Doppelsträngige ribonukleinsäure mit verbesserter wirksamkeit in einem organismus |
EP2336317A1 (de) * | 2003-06-13 | 2011-06-22 | Alnylam Europe AG | Doppelsträngige Ribonukleinsäure mit gesteigerter Wirksamkeit in einem Organismus |
US7786290B2 (en) | 2003-06-13 | 2010-08-31 | Alnylam Pharmaceuticals, Inc. | Double-stranded ribonucleic acid with increased effectiveness in an organism |
EP1633770A4 (de) * | 2003-06-13 | 2008-04-16 | Alnylam Europe Ag | Doppelsträngige ribonukleinsäure mit verbesserter wirksamkeit in einem organismus |
EP1486564A1 (de) * | 2003-06-13 | 2004-12-15 | Ribopharma AG | SiRNA mit erhöhter Stabilität in Serum |
US9434943B2 (en) | 2003-09-12 | 2016-09-06 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
US11299734B2 (en) | 2003-09-12 | 2022-04-12 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
US10344277B2 (en) | 2003-09-12 | 2019-07-09 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
US10385339B2 (en) | 2003-12-22 | 2019-08-20 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA |
US9879253B2 (en) | 2003-12-22 | 2018-01-30 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA |
US7858769B2 (en) | 2004-02-10 | 2010-12-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional siNA) |
US8476245B2 (en) | 2004-02-11 | 2013-07-02 | University Of Tennessee Research Foundation | Inhibition of tumor growth and invasion by anti matrix metalloproteinase DNAzymes |
US8946402B2 (en) | 2004-04-23 | 2015-02-03 | The Trustees Of Columbia University In The City Of New York | Inhibition of hairless protein mRNA |
US8329667B2 (en) | 2004-04-23 | 2012-12-11 | The Trustees Of Columbia University In The City Of New York | Inhibition of hairless protein mRNA |
WO2005118787A2 (en) | 2004-05-10 | 2005-12-15 | The University Of North Carolina At Chapel Hill | Method of screening candidate compounds for susceptibility to biliary excretion |
US10508277B2 (en) | 2004-05-24 | 2019-12-17 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
EP2484780A1 (de) | 2004-07-23 | 2012-08-08 | The University of North Carolina At Chapel Hill | Verfahren und Materialien zur Bestimmung der Schmerzempfindlichkeit und Vorhersage und Behandlung zugehöriger Störungen |
US7655768B2 (en) | 2004-08-26 | 2010-02-02 | Nippon Shinyaku Co., Ltd. | Galactose derivative, drug carrier and medicinal composition |
EP1799270A2 (de) * | 2004-09-15 | 2007-06-27 | Alnylam Pharmaceuticals Inc. | Zusammensetzungen und verfahren zur expressionshemmung von antiapoptotischen genen |
EP1799270A4 (de) * | 2004-09-15 | 2008-06-25 | Alnylam Pharmaceuticals Inc | Zusammensetzungen und verfahren zur expressionshemmung von antiapoptotischen genen |
AU2005284729B2 (en) * | 2004-09-15 | 2011-12-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
US8703769B2 (en) | 2005-07-15 | 2014-04-22 | The University Of North Carolina At Chapel Hill | Use of EGFR inhibitors to prevent or treat obesity |
US9914924B2 (en) | 2005-08-18 | 2018-03-13 | University Of Massachusetts | Methods and compositions for treating neurological disease |
EP2980220A1 (de) | 2005-09-20 | 2016-02-03 | BASF Plant Science GmbH | Verbesserte verfahren zur steuerung der genexpression |
US8309533B2 (en) | 2005-09-30 | 2012-11-13 | University Of Massachusetts | Allele-specific RNA interference |
US8093369B2 (en) | 2005-10-11 | 2012-01-10 | Ben Gurion University Of The Negev Research And Development Authority Ltd. | Compositions for silencing the expression of VDAC1 and uses thereof |
WO2007099981A1 (ja) | 2006-03-01 | 2007-09-07 | Nippon Shinyaku Co., Ltd. | ガラクトース誘導体、薬物担体及び医薬組成物 |
EP2292739A1 (de) | 2006-03-24 | 2011-03-09 | Institut National De La Recherche Agronomique | Verfahrung zur Herstellung differenzierter Zellen vom Huhn, und Gene, die im Erhalt der Pluripotenz impliziert sind |
WO2008092153A2 (en) | 2007-01-26 | 2008-07-31 | University Of Louisville Research Foundation, Inc. | Modification of exosomal components for use as a vaccine |
WO2008116094A2 (en) | 2007-03-21 | 2008-09-25 | Brookhaven Science Associates, Llc | Combined hairpin-antisense compositions and methods for modulating expression |
US9193972B2 (en) | 2007-03-21 | 2015-11-24 | Brookhaven Science Associates, Llc | Combined hairpin-antisense compositions and methods for modulating expression |
US8796442B2 (en) | 2007-03-21 | 2014-08-05 | Brookhaven Science Associates, Llc. | Combined hairpin-antisense compositions and methods for modulating expression |
US8470792B2 (en) | 2008-12-04 | 2013-06-25 | Opko Pharmaceuticals, Llc. | Compositions and methods for selective inhibition of VEGF |
FR2944437A1 (fr) * | 2009-04-16 | 2010-10-22 | Oreal | Utilisation d'inhibiteurs de l'expression d'hif 1 alpha pour proteger la peau des dommages deleteres induits par le rayonnement uva |
EP2484385A1 (de) * | 2009-10-01 | 2012-08-08 | Tokyo Women's Medical University | Zusammensetzung zur behandlung von pankreaskrebs |
JP2011074040A (ja) * | 2009-10-01 | 2011-04-14 | Tokyo Women's Medical College | 膵臓がん治療用の組成物 |
EP2484385A4 (de) * | 2009-10-01 | 2013-10-30 | Univ Tokyo Womens Medical | Zusammensetzung zur behandlung von pankreaskrebs |
EP3766976A1 (de) | 2009-12-18 | 2021-01-20 | Arrowhead Pharmaceuticals, Inc. | Organische zusammensetzungen zur behandlung von hsf1-bedingten erkrankungen |
WO2011073326A2 (en) | 2009-12-18 | 2011-06-23 | Novartis Ag | Organic compositions to treat hsf1-related diseases |
EP3406720A1 (de) | 2009-12-18 | 2018-11-28 | Arrowhead Pharmaceuticals, Inc. | Organische zusammensetzungen zur behandlung von hsf1-bedingten erkrankungen |
EP3000885A2 (de) | 2009-12-18 | 2016-03-30 | Arrowhead Research Corporation | Organische zusammensetzungen zur behandlung von hsf1-bedingten erkrankungen |
WO2011098449A1 (en) | 2010-02-10 | 2011-08-18 | Novartis Ag | Methods and compounds for muscle growth |
US10584335B2 (en) | 2010-08-24 | 2020-03-10 | Sirna Therapeutics, Inc. | Single-stranded RNAi agents containing an internal, non-nucleic acid spacer |
US9243246B2 (en) | 2010-08-24 | 2016-01-26 | Sirna Therapeutics, Inc. | Single-stranded RNAi agents containing an internal, non-nucleic acid spacer |
US9845466B2 (en) | 2010-08-24 | 2017-12-19 | Sirna Therapeutics, Inc. | Single-stranded RNAi agents containing an internal, non-nucleic acid spacer |
EP2433644A1 (de) | 2010-09-22 | 2012-03-28 | IMBA-Institut für Molekulare Biotechnologie GmbH | Brustkrebstherapeutika |
WO2012038504A2 (en) | 2010-09-22 | 2012-03-29 | Imba - Institut Für Molekulare Biotechnologie Gmbh | Breast cancer therapeutics |
US9970005B2 (en) | 2010-10-29 | 2018-05-15 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA) |
US11932854B2 (en) | 2010-10-29 | 2024-03-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA) |
US11193126B2 (en) | 2010-10-29 | 2021-12-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA) |
WO2013105022A2 (en) | 2012-01-09 | 2013-07-18 | Novartis Ag | Organic compositions to treat beta-catenin-related diseases |
EP2700949A1 (de) | 2012-08-24 | 2014-02-26 | IMG Institut für medizinische Genomforschung Planungsgesellschaft M.B.H. | Verwendung von Biliverdinreduktaseproteinen als Krebsmarker |
EP3693384A1 (de) | 2014-03-11 | 2020-08-12 | Cellectis | Verfahren zur erzeugung von t-zellen mit kompatibilität für allogene transplantation |
US11111497B2 (en) | 2014-11-12 | 2021-09-07 | Nmc, Inc. | Transgenic plants with engineered redox sensitive modulation of photosynthetic antenna complex pigments and methods for making the same |
US10745708B2 (en) | 2014-11-12 | 2020-08-18 | Nmc, Inc. | Transgenic plants with engineered redox sensitive modulation of photosynthetic antenna complex pigments and methods for making the same |
WO2016077624A1 (en) | 2014-11-12 | 2016-05-19 | Nmc, Inc. | Transgenic plants with engineered redox sensitive modulation of photosynthetic antenna complex pigments and methods for making the same |
WO2016140921A1 (en) | 2015-03-02 | 2016-09-09 | 180 Therapeutics Lp | Method of treating a localized fibrotic disorder using an il-33 antagonist |
WO2017152073A1 (en) | 2016-03-04 | 2017-09-08 | University Of Louisville Research Foundation, Inc. | Methods and compositions for ex vivo expansion of very small embryonic-like stem cells (vsels) |
WO2018020012A1 (en) | 2016-07-29 | 2018-02-01 | Danmarks Tekniske Universitet | Methods for decoupling cell growth from production of biochemicals and recombinant polypeptides |
WO2018229251A1 (en) | 2017-06-16 | 2018-12-20 | Imba - Institut Für Molekulare Biotechnologie Gmbh | Blood vessel organoid, methods of producing and using said organoids |
Also Published As
Publication number | Publication date |
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WO2002055692A3 (de) | 2003-06-12 |
ATE460481T1 (de) | 2010-03-15 |
US20040001811A1 (en) | 2004-01-01 |
JP4209678B2 (ja) | 2009-01-14 |
EP1349927A2 (de) | 2003-10-08 |
EP2365075A1 (de) | 2011-09-14 |
EP2213736A3 (de) | 2010-09-01 |
CA2432341A1 (en) | 2002-07-18 |
JP2004519457A (ja) | 2004-07-02 |
ZA200304127B (en) | 2004-05-11 |
ES2204360T3 (es) | 2010-07-06 |
US7473525B2 (en) | 2009-01-06 |
ZA200304500B (en) | 2003-11-18 |
CN1650010A (zh) | 2005-08-03 |
EP2213736A2 (de) | 2010-08-04 |
DE10100586C1 (de) | 2002-04-11 |
EP1349927B1 (de) | 2010-03-10 |
ES2204360T1 (es) | 2004-05-01 |
DE50214266D1 (de) | 2010-04-22 |
EP2213736B1 (de) | 2018-03-07 |
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