BR9914773A - Set of generic elements, method for the production of single-stranded DNA, mrna transcription, nucleic acid construction, ssdna transcription, vector, vector system, host cell, set for the production of a single-stranded nucleic acid sequence, method for in vivo or in vitro production of a single-stranded nucleic acid sequence, transcription of single-stranded cdna, inhibitory nucleic acid, heteroduplex molecule, and pharmaceutical composition - Google Patents

Set of generic elements, method for the production of single-stranded DNA, mrna transcription, nucleic acid construction, ssdna transcription, vector, vector system, host cell, set for the production of a single-stranded nucleic acid sequence, method for in vivo or in vitro production of a single-stranded nucleic acid sequence, transcription of single-stranded cdna, inhibitory nucleic acid, heteroduplex molecule, and pharmaceutical composition

Info

Publication number
BR9914773A
BR9914773A BR9914773-4A BR9914773A BR9914773A BR 9914773 A BR9914773 A BR 9914773A BR 9914773 A BR9914773 A BR 9914773A BR 9914773 A BR9914773 A BR 9914773A
Authority
BR
Brazil
Prior art keywords
nucleic acid
stranded
cdna
transcription
production
Prior art date
Application number
BR9914773-4A
Other languages
Portuguese (pt)
Inventor
Charles A Conrad
Original Assignee
Ingene Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ingene Inc filed Critical Ingene Inc
Publication of BR9914773A publication Critical patent/BR9914773A/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • C12N2310/111Antisense spanning the whole gene, or a large part of it
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/12Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/50Physical structure
    • C12N2310/53Physical structure partially self-complementary or closed

Landscapes

  • Genetics & Genomics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

"CONJUNTO DE ELEMENTOS GENéTICOS, 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". Métodos e composições para a produção de cDNA de um único filamento (ss-cDNA) em células eucarióticas, especificamente um cassete de DNA que produz s-cDNA in vivo O cassete contém o gene de codificação de transcriptase/Rnase H reversa do vírus de leucemia de murinos de Moloney, um gene de endonuclease de restrição de bactérias, e uma seq³ência de interesse que produz um modelo de RNA a partir do qual a transcriptase reversa sintetiza o ss-cDNA de uma seq³ência específica. O ss-cDNA é então modificado para remover todas as seq³ências de vetores de flanqueamento ao tirar vantagem da estrutura de "haste-laço" do ss-cDNA, que se forma como resultado da inclusão de uma repetição em tandem invertida que permite que o ss-cDNA de dobre de volta sobre si mesmo, formando uma haste de DNA de filamento duplo, na seq³ência de interesse. A haste de filamento duplo contém um ou mais elementos genéticos funcionais, tais como um sítio de reconhecimento de endonuclease de restrição e o laço, que continua como ss-cDNA, compreende qualquer seq³ência de nucleotídeos desejada. Esse desenho permite que a haste de filamento duplo do intermediário de haste-laço a ser clivada pela(s) endonuclease(s) de restrição correspondente(s) desejada(s) específica(s) para o sítio na haste e na porção do laço, ou seq³ência de interesse, seja então liberada como um pedaço de DNA de um único filamento linearizado. Esse pedaço de ss-DNA liberado (ou clivado) contém informações mínimas, caso haja alguma, sobre a seq³ência tanto a montante da posição 51 quanto a jusante da posição 3' em relação à porção da haste de filamento duplo anterior que contém o sítio de corte de endonuclease de restrição. As transfecções in vivo utilizando o sistema de vetores de DNA aqui descrito demonstram o uso desse sistema para produzir ss-DNA em células hospedeiras."SET OF GENETIC ELEMENTS, METHOD FOR THE PRODUCTION OF SINGLE CORD DNA, MRNA TRANSCRIPTION, NUCLEIC ACID CONSTRUCTION, SDSNA TRANSCRIPTION, VECTOR, VECTOR SYSTEM, HOSPITAL CELL, NUCLEUM CUTTING UNIT , METHOD FOR THE IN VIVO OR IN VITRO PRODUCTION OF A SINGLE CORDANIC NUCLEIC ACID, TRANSCRIPTION OF SINGLE CORDANIC CDNA, INHIBITOR NUCLEIC ACID, HETERODUPLEX MOLECULE AND PHARMACEUTICAL COMPOSITION ". Methods and compositions for the production of single-strand cDNA (ss-cDNA) in eukaryotic cells, specifically a DNA cassette that produces s-cDNA in vivo The cassette contains the leukemia virus reverse transcriptase / R Hase encoding gene of Moloney murines, a bacterial restriction endonuclease gene, and a sequence of interest that produces an RNA model from which reverse transcriptase synthesizes the ss-cDNA of a specific sequence. The ss-cDNA is then modified to remove all flanking vector sequences by taking advantage of the ss-cDNA "rod-loop" structure, which is formed as a result of including an inverted tandem repeat that allows the ss -cDNA fold back on itself, forming a double-stranded DNA strand, in the sequence of interest. The double stranded rod contains one or more functional genetic elements, such as a restriction endonuclease recognition site and the loop, which continues as ss-cDNA, comprises any desired nucleotide sequence. This design allows the double-stranded rod of the rod-loop intermediate to be cleaved by the desired corresponding restriction endonuclease (s) specific to the site on the rod and portion of the loop , or sequence of interest, is then released as a piece of DNA from a single linearized strand. This piece of ss-DNA released (or cleaved) contains minimal information, if any, about the sequence both upstream of position 51 and downstream of position 3 'in relation to the portion of the anterior double-stranded rod containing the site of restriction endonuclease cut. In vivo transfections using the DNA vector system described here demonstrate the use of this system to produce ss-DNA in host cells.

BR9914773-4A 1998-10-09 1999-10-12 Set of generic elements, method for the production of single-stranded DNA, mrna transcription, nucleic acid construction, ssdna transcription, vector, vector system, host cell, set for the production of a single-stranded nucleic acid sequence, method for in vivo or in vitro production of a single-stranded nucleic acid sequence, transcription of single-stranded cdna, inhibitory nucleic acid, heteroduplex molecule, and pharmaceutical composition BR9914773A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US16979398A 1998-10-09 1998-10-09
US39778299A 1999-09-16 1999-09-16
PCT/US1999/023936 WO2000022114A1 (en) 1998-10-09 1999-10-12 PRODUCTION OF ssDNA $i(IN VIVO)

Publications (1)

Publication Number Publication Date
BR9914773A true BR9914773A (en) 2002-02-05

Family

ID=26865380

Family Applications (1)

Application Number Title Priority Date Filing Date
BR9914773-4A BR9914773A (en) 1998-10-09 1999-10-12 Set of generic elements, method for the production of single-stranded DNA, mrna transcription, nucleic acid construction, ssdna transcription, vector, vector system, host cell, set for the production of a single-stranded nucleic acid sequence, method for in vivo or in vitro production of a single-stranded nucleic acid sequence, transcription of single-stranded cdna, inhibitory nucleic acid, heteroduplex molecule, and pharmaceutical composition

Country Status (5)

Country Link
AU (1) AU6298899A (en)
BR (1) BR9914773A (en)
CA (1) CA2345936A1 (en)
MX (1) MXPA01003643A (en)
WO (1) WO2000022114A1 (en)

Families Citing this family (170)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19956568A1 (en) 1999-01-30 2000-08-17 Roland Kreutzer Method and medicament for inhibiting the expression of a given gene
US7419964B2 (en) 1999-09-16 2008-09-02 Cytogenix, Inc. Treatment of HSV-related pathologies using ssDNA
AU7855300A (en) * 1999-10-04 2001-05-10 Cytogenix, Inc. Altering gene expression with ssDNA produced in vivo
DE10100586C1 (en) 2001-01-09 2002-04-11 Ribopharma Ag Inhibiting gene expression in cells, useful for e.g. treating tumors, by introducing double-stranded complementary oligoRNA having unpaired terminal bases
AU2001277194A1 (en) * 2000-07-28 2002-02-13 Oligotrail, Llc. Transgenic identification markers
EP2322648A1 (en) 2000-09-26 2011-05-18 Duke University RNA aptamers and methods for identifying the same
US7423142B2 (en) 2001-01-09 2008-09-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
US7767802B2 (en) 2001-01-09 2010-08-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
SG157961A1 (en) 2001-05-25 2010-01-29 Univ Duke Modulators of pharmacological agents
US7745418B2 (en) 2001-10-12 2010-06-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting viral replication
AU2002363997A1 (en) * 2001-12-14 2003-06-30 Yale University Intracellular generation of single-stranded dna
WO2003093424A2 (en) * 2002-05-01 2003-11-13 Cytogenix, Inc. In vivo ssdna expression vectors for altering gene expression
US20050020526A1 (en) * 2003-06-03 2005-01-27 Cytogenix, Inc. Oligodeoxynucleotide intervention for prevention and treatment of sepsis
AU2005222902B2 (en) 2004-03-12 2010-06-10 Alnylam Pharmaceuticals, Inc. iRNA agents targeting VEGF
ES2494940T3 (en) 2004-04-22 2014-09-16 Regado Biosciences, Inc. Enhanced coagulation factor modulators
JP2008514204A (en) * 2004-09-28 2008-05-08 サイトジェニックス, インコーポレイテッド Single-stranded antibacterial oligonucleotide and use thereof
US20100069461A1 (en) 2005-11-09 2010-03-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor v leiden mutant gene
US8658608B2 (en) 2005-11-23 2014-02-25 Yale University Modified triple-helix forming oligonucleotides for targeted mutagenesis
CA2647728C (en) 2006-03-31 2014-12-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of eg5 gene
EP2013222B1 (en) 2006-04-28 2013-02-13 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of a gene from the jc virus
EP2835429B1 (en) 2006-05-11 2017-12-13 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
EP2023937B1 (en) 2006-05-19 2011-10-12 Alnylam Pharmaceuticals Inc. Rnai modulation of aha and therapeutic uses thereof
US7888498B2 (en) 2006-05-22 2011-02-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of IKK-B gene
WO2008036638A2 (en) 2006-09-18 2008-03-27 Alnylam Pharmaceuticals, Inc. Rnai modulation of scap and therapeutic uses thereof
CA2663581C (en) 2006-09-21 2016-03-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the hamp gene
PE20090064A1 (en) 2007-03-26 2009-03-02 Novartis Ag DOUBLE-CHAIN RIBONUCLEIC ACID TO INHIBIT THE EXPRESSION OF THE HUMAN E6AP GENE AND THE PHARMACEUTICAL COMPOSITION THAT INCLUDES IT
EA201000085A1 (en) 2007-07-05 2010-10-29 Новартис Аг dsPHK INTRODUCED FOR THE TREATMENT OF VIRAL INFECTION
US7871985B2 (en) 2007-12-10 2011-01-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor VII gene
EA201301171A1 (en) 2008-03-05 2014-10-30 Элнилэм Фармасьютикалз, Инк. COMPOSITIONS AND METHODS OF INHIBITING EXPRESSION OF EG5 AND VEGF GENES
EP2690175B1 (en) 2008-09-02 2016-12-28 Alnylam Pharmaceuticals, Inc. Compositions and methods for combined inhibition of mutant EGFR gene and IL-6 expression
EP3584320A1 (en) 2008-09-25 2019-12-25 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene
DK2344639T3 (en) 2008-10-20 2015-07-27 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF TRANSTHYRETINE
AU2009324534B2 (en) 2008-12-10 2015-07-30 Alnylam Pharmaceuticals, Inc. GNAQ targeted dsRNA compositions and methods for inhibiting expression
US20120041051A1 (en) 2009-02-26 2012-02-16 Kevin Fitzgerald Compositions And Methods For Inhibiting Expression Of MIG-12 Gene
CN104922699B (en) 2009-03-12 2020-07-24 阿尔尼拉姆医药品有限公司 Lipid formulated compositions and methods for inhibiting the expression of Eg5 and VEGF genes
MX2011013421A (en) 2009-06-15 2012-03-16 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene.
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
ES2893199T3 (en) 2010-03-29 2022-02-08 Alnylam Pharmaceuticals Inc dsRNA therapy for transthyretin (TTR)-related ocular amyloidosis
AU2011261434B2 (en) 2010-06-02 2015-11-26 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
US9193973B2 (en) 2010-12-10 2015-11-24 Alynylam Pharmaceuticals, Inc. Compositions and methods for increasing erythropoietin (EPO) production
EP2648763A4 (en) 2010-12-10 2014-05-14 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of klf-1 and bcl11a genes
BR112013025006B1 (en) 2011-03-29 2021-06-15 Alnylam Pharmaceuticals, Inc PHARMACEUTICAL COMPOSITION TO INHIBIT THE EXPRESSION OF A TMPRSS6 GENE, METHOD FOR INHIBITING TMPRSS6 EXPRESSION IN A CELL, AND USE OF DOUBLE TAPE RIBONU-CLEIC ACIDS
JP2014526882A (en) 2011-06-21 2014-10-09 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 Assays and methods for determining the activity of therapeutic agents in a subject
KR20230084331A (en) 2011-06-21 2023-06-12 알닐람 파마슈티칼스 인코포레이티드 Compositions and methods for inhibition of expression of apolipoprotein c-iii(apoc3) genes
EP2723351B1 (en) 2011-06-21 2018-02-14 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of protein c (proc) genes
EP2723861A4 (en) 2011-06-21 2014-12-10 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting hepcidin antimicrobial peptide (hamp) or hamp-related gene expression
BR122019026068B8 (en) 2011-06-21 2022-10-18 Alnylam Pharmaceuticals DOUBLE-STRAND RIBONUCLEIC ACID (DSRNA) FOR INHIBITING ANGPTL3 EXPRESSION AND ITS USE, PHARMACEUTICAL COMPOSITION AND IN VITRO METHOD FOR INHIBITING ANGPTL3 EXPRESSION IN A CELL
US20140235693A1 (en) 2011-06-23 2014-08-21 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
EP2739735A2 (en) 2011-08-01 2014-06-11 Alnylam Pharmaceuticals, Inc. Method for improving the success rate of hematopoietic stem cell transplants
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
US9127274B2 (en) 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
EP3336187A1 (en) 2012-12-05 2018-06-20 Alnylam Pharmaceuticals, Inc. Pcsk9 irna compositions and methods of use thereof
WO2014130922A1 (en) 2013-02-25 2014-08-28 Trustees Of Boston University Compositions and methods for treating fungal infections
WO2014160418A2 (en) 2013-03-13 2014-10-02 GeneWeave Biosciences, Inc. Non-replicative transduction particles and transduction particle-based reporter systems
SG11201507400SA (en) 2013-03-14 2015-10-29 Alnylam Pharmaceuticals Inc Complement component c5 irna compositions and methods of use thereof
EP2978446B1 (en) 2013-03-27 2020-03-04 The General Hospital Corporation Anti-cd33 antibody for use in treating alzheimer's disease
US10246708B2 (en) 2013-05-06 2019-04-02 Alnylam Pharmaceuticals, Inc. Dosages and methods for delivering lipid formulated nucleic acid molecules
LT2999785T (en) 2013-05-22 2018-07-25 Alnylam Pharmaceuticals, Inc. SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
TW202342750A (en) 2013-05-22 2023-11-01 美商阿尼拉製藥公司 Tmprss6 irna compositions and methods of use thereof
US10077444B2 (en) 2013-10-02 2018-09-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the LECT2 gene
IL282747B2 (en) 2013-10-04 2023-10-01 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of the alas1 gene
IL294470A (en) 2013-12-12 2022-09-01 Alnylam Pharmaceuticals Inc Complement component irna compositions and methods of use thereof
CA2938857A1 (en) 2014-02-11 2015-08-20 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
WO2015175510A1 (en) 2014-05-12 2015-11-19 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a serpinc1-associated disorder
CN112301031A (en) 2014-05-22 2021-02-02 阿尔尼拉姆医药品有限公司 Angiotensinogen (AGT) iRNA compositions and methods of use thereof
JOP20200115A1 (en) 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc Compositions And Methods For Inhibition Of HAO1 (Hydroxyacid Oxidase 1 (Glycolate Oxidase)) Gene Expression
JOP20200092A1 (en) 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc HEPATITIS B VIRUS (HBV) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP3221451A1 (en) 2014-11-17 2017-09-27 Alnylam Pharmaceuticals, Inc. Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof
CA2976445A1 (en) 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
JP6975641B2 (en) 2015-04-13 2021-12-01 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. Angiopoetin-like 3 (ANGPTL3) iRNA compositions and their use
EA201792444A1 (en) 2015-05-06 2018-06-29 Элнилэм Фармасьютикалз, Инк. COMPOSITIONS ON THE BASIS OF IRNA FOR FACTOR XII (HAGEMAN FACTOR) (F12), PLASMA KALLIKREIN B (FLETCH FACTOR) 1 (KLKB1) AND KININOGEN 1 (KNG1) AND FOSTER OF THE FLETCHER) (1)
WO2016201301A1 (en) 2015-06-12 2016-12-15 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions and methods of use thereof
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
WO2017011286A1 (en) 2015-07-10 2017-01-19 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof
PE20181131A1 (en) 2015-09-02 2018-07-17 Alnylam Pharmaceuticals Inc RNAi COMPOSITIONS FOR PROGRAMMED CELL DEATH 1 (PD-L1) LINK 1 (PD-L1) AND METHODS OF USE OF THEM
TW201718857A (en) 2015-09-14 2017-06-01 艾爾妮蘭製藥公司 Compositions and methods for inhibiting expression of the ALAS1 gene
SG11201804729RA (en) 2015-12-07 2018-07-30 Genzyme Corp Methods and compositions for treating a serpinc1-associated disorder
WO2017100542A1 (en) 2015-12-10 2017-06-15 Alnylam Pharmaceuticals, Inc. Sterol regulatory element binding protein (srebp) chaperone (scap) irna compositions and methods of use thereof
JP2019508037A (en) 2016-02-16 2019-03-28 イェール ユニバーシティーYale Universit Compositions for enhancing targeted gene editing and methods of use thereof
MA45295A (en) 2016-04-19 2019-02-27 Alnylam Pharmaceuticals Inc HIGH DENSITY LIPOPROTEIN BINDING PROTEIN (HDLBP / VIGILINE) RNA COMPOSITION AND METHODS FOR USING THEM
JP2019518028A (en) 2016-06-10 2019-06-27 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Alnylam Pharmaceuticals, Inc. Complement component C5i RNA composition and its use for treating paroxysmal nocturnal hemoglobinuria (PNH)
TWI788312B (en) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
SG10201913552UA (en) 2016-12-16 2020-03-30 Alnylam Pharmaceuticals Inc Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
BR112019021852A2 (en) 2017-04-18 2020-06-02 Alnylam Pharmaceuticals, Inc. RNAI AGENT AND A VACCINE AGAINST HBV, USE OR METHOD AND KIT FOR TREATMENT
AU2018301477A1 (en) 2017-07-13 2020-02-27 Alnylam Pharmaceuticals Inc. Lactate dehydrogenase a (LDHA) iRNA compositions and methods of use thereof
CA3078971A1 (en) 2017-11-01 2019-05-09 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
WO2019099610A1 (en) 2017-11-16 2019-05-23 Alnylam Pharmaceuticals, Inc. Kisspeptin 1 (kiss1) irna compositions and methods of use thereof
EP3714054A1 (en) 2017-11-20 2020-09-30 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
MX2020006012A (en) 2017-12-18 2020-09-14 Alnylam Pharmaceuticals Inc High mobility group box-1 (hmgb1) irna compositions and methods of use thereof.
US11008602B2 (en) 2017-12-20 2021-05-18 Roche Molecular Systems, Inc. Non-replicative transduction particles and transduction particle-based reporter systems
TW202016304A (en) 2018-05-14 2020-05-01 美商阿尼拉製藥公司 Angiotensinogen (agt) irna compositions and methods of use thereof
TW202020157A (en) 2018-08-16 2020-06-01 美商艾爾妮蘭製藥公司 Compositions and methods for inhibiting expression of the lect2 gene
JP2022500003A (en) 2018-09-18 2022-01-04 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. Ketohexokinase (KHK) iRNA composition and its usage
CN113166760A (en) 2018-11-23 2021-07-23 赛诺菲 Novel RNA compositions and methods for inhibiting ANGPTL8
WO2020136154A1 (en) 2018-12-27 2020-07-02 F. Hoffmann-La Roche Ag Non-replicative transduction particles and transduction particle-based reporter systems for detection of acinetobacter baumannii
US11572595B2 (en) 2018-12-31 2023-02-07 Roche Molecular Systems, Inc. Non-replicative transduction particles with one or more non-native tail fibers and transduction particle-based reporter systems
EP4007811A2 (en) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Carboxypeptidase b2 (cpb2) irna compositions and methods of use thereof
EP4007812A1 (en) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Serpin family f member 2 (serpinf2) irna compositions and methods of use thereof
EP4013870A1 (en) 2019-08-13 2022-06-22 Alnylam Pharmaceuticals, Inc. Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof
CN115176011A (en) 2019-08-27 2022-10-11 赛诺菲 Compositions and methods for inhibiting PCSK9
MX2022002689A (en) 2019-09-03 2022-04-07 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of the lect2 gene.
EP4048807A1 (en) 2019-09-23 2022-08-31 Omega Therapeutics, Inc. Compositions and methods for modulating apolipoprotein b (apob) gene expression
CA3147643A1 (en) 2019-09-23 2021-04-01 Omega Therapeutics, Inc. Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (hnf4.alpha.) gene expression
EP4038189A1 (en) 2019-10-04 2022-08-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing ugt1a1 gene expression
AU2020363372A1 (en) 2019-10-07 2022-05-19 University Of Virginia Patent Foundation Modulating lymphatic vessels in neurological disease
US20240141358A1 (en) 2019-10-18 2024-05-02 Alnylam Pharmaceuticals, Inc. Solute carrier family member irna compositions and methods of use thereof
KR20220084399A (en) 2019-10-22 2022-06-21 알닐람 파마슈티칼스 인코포레이티드 Complement component C3 iRNA compositions and methods of use thereof
MX2022004388A (en) 2019-11-01 2022-05-06 Alnylam Pharmaceuticals Inc HUNTINGTIN (HTT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF.
EP4051796A1 (en) 2019-11-01 2022-09-07 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing dnajb1-prkaca fusion gene expression
EP4058577A1 (en) 2019-11-13 2022-09-21 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating an angiotensinogen- (agt-) associated disorder
US20230056569A1 (en) 2019-11-22 2023-02-23 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
IL293824A (en) 2019-12-13 2022-08-01 Alnylam Pharmaceuticals Inc Human chromosome 9 open reading frame 72 (c9orf72) irna agent compositions and methods of use thereof
WO2021126734A1 (en) 2019-12-16 2021-06-24 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
US20220356537A1 (en) 2019-12-31 2022-11-10 Roche Molecular Systems, Inc. Quantitative pcr screening of inducible prophage from bacterial isolates
EP4093426A1 (en) 2020-01-24 2022-11-30 University of Virginia Patent Foundation Modulating lymphatic vessels in neurological disease
WO2021154941A1 (en) 2020-01-31 2021-08-05 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als)
JP2023514190A (en) 2020-02-10 2023-04-05 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 Compositions and methods for silencing VEGF-A expression
KR20220143106A (en) 2020-02-18 2022-10-24 알닐람 파마슈티칼스 인코포레이티드 Apolipoprotein C3 (APOC3) iRNA composition and method of use thereof
MX2022011009A (en) 2020-03-06 2022-10-07 Alnylam Pharmaceuticals Inc KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF.
CA3173528A1 (en) 2020-03-11 2021-09-16 Omega Therapeutics, Inc. Compositions and methods for modulating forkhead box p3 (foxp3) gene expression
WO2021188611A1 (en) 2020-03-18 2021-09-23 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
TW202204615A (en) 2020-03-26 2022-02-01 美商阿尼拉製藥公司 Coronavirus irna compositions and methods of use thereof
WO2021202443A2 (en) 2020-03-30 2021-10-07 Alnylam Pharmaceucticals, Inc. Compositions and methods for silencing dnajc15 gene expression
CA3179411A1 (en) 2020-04-06 2021-10-14 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing myoc expression
EP4133076A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof
EP4133077A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
CN116134135A (en) 2020-04-07 2023-05-16 阿尔尼拉姆医药品有限公司 Compositions and methods for silencing SCN9A expression
EP4143319A1 (en) 2020-04-27 2023-03-08 Alnylam Pharmaceuticals, Inc. Apolipoprotein e (apoe) irna agent compositions and methods of use thereof
IL297680A (en) 2020-04-30 2022-12-01 Alnylam Pharmaceuticals Inc Complement factor b (cfb) irna compositions and methods of use thereof
WO2021237097A1 (en) 2020-05-21 2021-11-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting marc1 gene expression
WO2021257782A1 (en) 2020-06-18 2021-12-23 Alnylam Pharmaceuticals, Inc. XANTHINE DEHYDROGENASE (XDH) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4217489A1 (en) 2020-09-24 2023-08-02 Alnylam Pharmaceuticals, Inc. Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof
EP4225917A1 (en) 2020-10-05 2023-08-16 Alnylam Pharmaceuticals, Inc. G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof
US20230383294A1 (en) 2020-10-16 2023-11-30 Sanofi Novel rna compositions and methods for inhibiting angptl3
EP4229201A1 (en) 2020-10-16 2023-08-23 Sanofi Rna compositions and methods for inhibiting lipoprotein(a)
AU2021365822A1 (en) 2020-10-21 2023-06-08 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating primary hyperoxaluria
EP4232582A1 (en) 2020-10-23 2023-08-30 Alnylam Pharmaceuticals, Inc. Mucin 5b (muc5b) irna compositions and methods of use thereof
CA3200595A1 (en) 2020-11-13 2022-05-19 Alnylam Pharmaceuticals, Inc. Coagulation factor v (f5) irna compositions and methods of use thereof
AU2021393417A1 (en) 2020-12-01 2023-06-29 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
EP4259795A1 (en) 2020-12-08 2023-10-18 Alnylam Pharmaceuticals, Inc. Coagulation factor x (f10) irna compositions and methods of use thereof
EP4274896A1 (en) 2021-01-05 2023-11-15 Alnylam Pharmaceuticals, Inc. Complement component 9 (c9) irna compositions and methods of use thereof
EP4291654A2 (en) 2021-02-12 2023-12-20 Alnylam Pharmaceuticals, Inc. Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
JP2024509783A (en) 2021-02-25 2024-03-05 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 Prion protein (PRNP) IRNA compositions and methods of use thereof
TW202302847A (en) 2021-02-26 2023-01-16 美商艾拉倫製藥股份有限公司 Ketohexokinase (khk) irna compositions and methods of use thereof
IL305442A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like3 (angptl3) irna compositions and method of use thereof
EP4305169A1 (en) 2021-03-12 2024-01-17 Alnylam Pharmaceuticals, Inc. Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof
CA3214499A1 (en) 2021-03-29 2022-10-06 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof
EP4314293A1 (en) 2021-04-01 2024-02-07 Alnylam Pharmaceuticals, Inc. Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof
BR112023022284A2 (en) 2021-04-26 2023-12-26 Alnylam Pharmaceuticals Inc COMPOSITIONS OF TRANSMEMBRANE PROTEASE IRNA, SERINE 6 (TMPRSS6) AND METHODS OF USE THEREOF
JP2024519293A (en) 2021-04-29 2024-05-10 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 Signal Transducer and Activator of Transcription 6 (STAT6) iRNA Compositions and Methods of Use Thereof
EP4341401A1 (en) 2021-05-18 2024-03-27 Alnylam Pharmaceuticals, Inc. Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof
TW202317762A (en) 2021-06-02 2023-05-01 美商艾拉倫製藥股份有限公司 Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
CN117561334A (en) 2021-06-04 2024-02-13 阿尔尼拉姆医药品有限公司 Human chromosome 9 open reading frame 72 (C9 ORF 72) iRNA pharmaceutical compositions and methods of use thereof
EP4351541A2 (en) 2021-06-08 2024-04-17 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
CA3225469A1 (en) 2021-06-30 2023-01-05 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating an angiotensinogen- (agt-) associated disorder
EP4367242A2 (en) 2021-07-07 2024-05-15 Omega Therapeutics, Inc. Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression
EP4373934A1 (en) 2021-07-19 2024-05-29 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder
EP4373937A1 (en) 2021-07-21 2024-05-29 Alnylam Pharmaceuticals, Inc. Metabolic disorder-associated target gene irna compositions and methods of use thereof
IL309905A (en) 2021-07-23 2024-03-01 Alnylam Pharmaceuticals Inc Beta-catenin (ctnnb1) irna compositions and methods of use thereof
WO2023009687A1 (en) 2021-07-29 2023-02-02 Alnylam Pharmaceuticals, Inc. 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof
WO2023014677A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
TW202337474A (en) 2021-08-04 2023-10-01 美商艾拉倫製藥股份有限公司 Irna compositions and methods for silencing angiotensinogen (agt)
AR126771A1 (en) 2021-08-13 2023-11-15 Alnylam Pharmaceuticals Inc RNAi COMPOSITIONS AGAINST FACTOR XII (F12) AND THEIR METHODS OF USE
WO2023044370A2 (en) 2021-09-17 2023-03-23 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing complement component 3 (c3)
WO2023044094A1 (en) 2021-09-20 2023-03-23 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
CA3234887A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
AR127477A1 (en) 2021-10-29 2024-01-31 Alnylam Pharmaceuticals Inc COMPOSITIONS OF RNAi AGAINST COMPLEMENT FACTOR B (CFB) AND METHODS OF USE THEREOF
WO2023076450A2 (en) 2021-10-29 2023-05-04 Alnylam Pharmaceuticals, Inc. HUNTINGTIN (HTT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
WO2024059165A1 (en) 2022-09-15 2024-03-21 Alnylam Pharmaceuticals, Inc. 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5436141A (en) * 1989-02-24 1995-07-25 University Of Medicine And Dentistry Of New Jersey Method for synthesizing stable single-stranded CDNA in eukaryotes by means of a bacterial retron and products
US5434070A (en) * 1989-02-24 1995-07-18 The University Of Medicine And Dentistry Of New Jersey Reverse transcriptases from Escherichia coli and Myxococcus xanthus
CA2073630C (en) * 1991-08-30 2007-12-11 Atsushi Ohshima Method for synthesizing single-stranded stem-loop dnas, the products and uses therefor
JP3089036B2 (en) * 1991-08-30 2000-09-18 ザ ユニバーシティー オブ メディシン アンド デンティストリー オブ ニュージャージー Overexpression of single-stranded molecules
JPH08501928A (en) * 1992-07-02 1996-03-05 ハイブライドン インコーポレイテッド Self-stabilizing oligonucleotides as therapeutic agents
CA2151484A1 (en) * 1992-12-09 1994-06-23 Jeffrey E. Miller Methods and compositions for cdna synthesis
FR2703053B1 (en) * 1993-03-26 1995-06-16 Genset Sa STAPLE AND SEMI-STAPLE OLIGONUCLEOTIDES, PREPARATION METHOD AND APPLICATIONS.
EP0781330A1 (en) * 1994-06-22 1997-07-02 Jeffrey E. Miller METHODS AND COMPOSITIONS FOR cDNA SYNTHESIS

Also Published As

Publication number Publication date
MXPA01003643A (en) 2003-07-21
WO2000022114A1 (en) 2000-04-20
AU6298899A (en) 2000-05-01
WO2000022114A9 (en) 2000-10-19
CA2345936A1 (en) 2000-04-20

Similar Documents

Publication Publication Date Title
BR9914773A (en) Set of generic elements, method for the production of single-stranded DNA, mrna transcription, nucleic acid construction, ssdna transcription, vector, vector system, host cell, set for the production of a single-stranded nucleic acid sequence, method for in vivo or in vitro production of a single-stranded nucleic acid sequence, transcription of single-stranded cdna, inhibitory nucleic acid, heteroduplex molecule, and pharmaceutical composition
Phylactou et al. Ribozyme-mediated trans-splicing of a trinucleotide repeat
Kumazawa et al. The complete nucleotide sequence of a snake (Dinodon semicarinatus) mitochondrial genome with two identical control regions
Wickstead et al. The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes
Garel et al. Selective digestion of transcriptionally active ovalbumin genes from oviduct nuclei.
Borovjagin et al. U3 small nucleolar RNA is essential for cleavage at sites 1, 2 and 3 in pre-rRNA and determines which rRNA processing pathway is taken in Xenopus oocytes
WO2003087301A3 (en) Methods and compositions for dna manipulation
BR0012325A (en) Methods and compositions for preventing the formation of abnormal RNA during the transcription of a plasmid sequence
EP3214177A3 (en) Methods and means for obtaining modified phenotypes
Donley et al. Asynchronous replication, mono-allelic expression, and long range cis-effects of ASAR6
Grams et al. Processing of polycistronic guide RNAs is associated with RNA editing complexes in Trypanosoma brucei
Genç et al. Methylation mosaicism of 5′-(CGG) n-3′ repeats in fragile X, premutation and normal individuals
Tinker et al. Induction of XIST expression from the human active X chromosome in mouse/human somatic cell hybrids by DNA demethylation
Denslow et al. Mechanism of mRNA binding to bovine mitochondrial ribosomes
Katayama et al. Editing of DNA methylation using CRISPR/Cas9 and a ssDNA template in human cells
Donehower et al. Identification of a conserved sequence in the non-coding regions of many human genes
Boss et al. Sequence of the yeast iso-1-cytochrome c mRNA.
CA3184882A1 (en) Compositions and methods for epigenome editing
Müller et al. Z-DNA-forming sites within the human beta-globin gene cluster.
Bach et al. Protein-RNA interactions in 20S U5 snRNPs
US20230332184A1 (en) Template guide rna molecules
Trembath et al. Analysis of two translocation breakpoints and identification of a negative regulatory element in patients with Rieger's syndrome
Matyášek et al. Unique epigenetic features of ribosomal RNA genes (rDNA) in early diverging plants (Bryophytes)
Juranek et al. De novo cytosine methylation in the differentiating macronucleus of the stichotrichous ciliate Stylonychia lemnae
Ma et al. Analysis of the Xist RNA isoforms suggests two distinctly different forms of regulation

Legal Events

Date Code Title Description
B06G Technical and formal requirements: other requirements [chapter 6.7 patent gazette]

Free format text: O DEPOSITANTE DEVERA APRESENTAR A PETICAO DEVIDA PARA O CUMPRIMENTO DESTAS EXIGENCIAS EM ATE 60 (SESSENTA) DIAS, CONTADOS A PARTIR DA DATA DE PUBLICACAO NA RPI.

B08F Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]

Free format text: REFERENTE AS 10A, 11A E 12A ANUIDADES.

B08K Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette]

Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2159 DE 22/05/2012.