WO1998011211A2 - METHOD FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES - Google Patents

METHOD FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES Download PDF

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Publication number
WO1998011211A2
WO1998011211A2 PCT/US1997/016017 US9716017W WO9811211A2 WO 1998011211 A2 WO1998011211 A2 WO 1998011211A2 US 9716017 W US9716017 W US 9716017W WO 9811211 A2 WO9811211 A2 WO 9811211A2
Authority
WO
WIPO (PCT)
Prior art keywords
cpg
oligonucleotides
oligonucleotide
phosphorothioate
gene expression
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1997/016017
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English (en)
French (fr)
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WO1998011211A3 (en
Inventor
Sudhir Agrawal
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aceragen Inc
Original Assignee
Hybridon 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
Priority to JP51382298A priority Critical patent/JP5265067B2/ja
Priority to AU43399/97A priority patent/AU4339997A/en
Priority to EP97941505A priority patent/EP0928335B1/en
Priority to DE69720481T priority patent/DE69720481T2/de
Priority to CA002265917A priority patent/CA2265917C/en
Priority to AT97941505T priority patent/ATE236248T1/de
Application filed by Hybridon Inc filed Critical Hybridon Inc
Priority to DK97941505T priority patent/DK0928335T3/da
Publication of WO1998011211A2 publication Critical patent/WO1998011211A2/en
Publication of WO1998011211A3 publication Critical patent/WO1998011211A3/en
Priority to US09/103,745 priority patent/US20030036516A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/311—Phosphotriesters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/312—Phosphonates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/314—Phosphoramidates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine

Definitions

  • USA 7j5: 280-284 and 285-288 (1978) disclose that a 13-mer synthetic oligonucleotide that is complementary to a part of the Rous sarcoma virus (RSV) genome can inhibit RSV replication in infected cell cultures and can inhibit RSV-mediated transformation of primary chick fibroblasts into malignant sarcoma cells. Since these early studies, the ability of antisense oligonucleotides to inhibit virus propagation has become firmly established.
  • US Patent No. 4,806,463 teaches that human immunodeficiency virus propagation can be inhibited by oligonucleotides that are complementary to any of various regions of the HIV genome. US Patent No.
  • all CpG dinucleosides present in the oligonucleotide are modified.
  • a CpG dinucleoside is "modified” if it is altered from the unmodified CpG dinucleoside such that it confers upon the oligonucleotide a reduced ability to cause splenomegaly and platelet depletion when administered to a mammal, relative to an otherwise identical oligonucleotide having an unmodified phosphorothioate CpG dinucleoside.
  • a 2 ' -O-substituted CpG is a CpG dinucleoside in which the 2 ' position of the pentose moiety is substituted, having an -O-lower alkyl group containing 1-6 saturated or unsaturated carbon atoms, or an -O-aryl or allyl group having 2-6 carbon atoms, wherein such alkyl, aryl or allyl group may be unsubstituted or may be substituted, e . g.
  • a 2 ' -5 ' CpG is a CpG dinucleoside in which the C nucleoside and the G nucleoside are covalently linked to each other through a 2 ' - ' internucleoside linkage.
  • the internucleoside linkage may be of any type, and is preferably a phosphorothioate or phosphodiester linkage.
  • compositions of the invention may be administered simultaneously, or sequentially a therapeutically effective amount of one or more of the therapeutic compositions of the invention to an individual as a single treatment episode.
  • the biological effects of splenomegaly, platelet depletion are reduced, relative to the same effects obtained upon administration of an otherwise identical composition containing the same quantity of an otherwise identical oligonucleotide, except that such oligonucleotide contains an unmodified CpG dinucleoside in place of the modified CpG dinucleoside.
  • This preferred biological effect can be monitored by measuring blood levels of platelets before and after oligonucleotide administration.
  • Oligonucleotide phosphorothioates were synthesized using an automated DNA synthesizer (Model 8700, Biosearch, Bedford, MA) using a beta-cyanoethyl phosphoramidite approach on a 10 micromole scale.
  • the intermediate phosphite linkage obtained after each coupling was oxidized using 3H, 1, 2-benzodithiole-3H-one-l, 1-dioxide (See Beaucage, In Protocols for Oligonucleotides and Analogs z Synthesis and Properties, Agrawal (editor) , Humana Press, Totowa, NJ, pp.
  • oligonucleotide was carried out according to standard procedures, (See Padmapriya et al . , Antisense Res. & Dev. 4.: 185-199 (1994)), except for oligonucleotides containing methylphosphonate-containing regions .
  • the CPG-bound oligonucleotide was treated with concentrated ammonium hydroxide for 1 hour at room temperature, and the supernatant was removed and evaporated to obtain a pale yellow residue, which was then treated with a mixture of ethylenedia ine/ethanol (1:1 v/v) for 6 hours at room temperature and dried again under reduced pressure .
  • CD-I mice and Fischer rats were injected intravenously daily for seven days with a dose ranging from 3-30 mg/kg body weight of CpG-containing phosphorothioate oligonucleotide, methylphosphonate CpG-containing phosphorothioate oligonucleotide, inverted CpG-containing phosphorothioate oligonucleotide, 5-methylC CpG-containing phosphorothioate oligonucleotide, 2 ' -O-substituted CpG, or saline as a control.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
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  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US1997/016017 1996-09-10 1997-09-10 METHOD FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES Ceased WO1998011211A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU43399/97A AU4339997A (en) 1996-09-10 1997-09-10 Method for using oligonucleotides having modified cpg dinucleosides
EP97941505A EP0928335B1 (en) 1996-09-10 1997-09-10 METHOD FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES
DE69720481T DE69720481T2 (de) 1996-09-10 1997-09-10 Verfahren zur verwendung von oligonukleotiden mit modifizierten cpg dinukleosiden
CA002265917A CA2265917C (en) 1996-09-10 1997-09-10 Method for using oligonucleotides having modified cpg dinucleosides
AT97941505T ATE236248T1 (de) 1996-09-10 1997-09-10 Verfahren zur verwendung von oligonukleotiden mit modifizierten cpg dinukleosiden
JP51382298A JP5265067B2 (ja) 1996-09-10 1997-09-10 修飾ＣｐＧジヌクレオシドを有するオリゴヌクレオチドの使用方法
DK97941505T DK0928335T3 (da) 1996-09-10 1997-09-10 Fremgangsmåde til anvendelse af oligonukleotider med modificerede CpG-dinukleosider
US09/103,745 US20030036516A1 (en) 1997-09-10 1998-06-24 Method for using oligonucleotides having modified cpg dinucleotides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/711,568 US5856462A (en) 1996-09-10 1996-09-10 Oligonucleotides having modified CpG dinucleosides
US08/711,568 1996-09-10

Publications (2)

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WO1998011211A2 true WO1998011211A2 (en) 1998-03-19
WO1998011211A3 WO1998011211A3 (en) 1998-04-16

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PCT/US1997/016017 Ceased WO1998011211A2 (en) 1996-09-10 1997-09-10 METHOD FOR USING OLIGONUCLEOTIDES HAVING MODIFIED CpG DINUCLEOSIDES

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US (1) US5856462A (enExample)
EP (1) EP0928335B1 (enExample)
JP (1) JP5265067B2 (enExample)
AT (1) ATE236248T1 (enExample)
AU (1) AU4339997A (enExample)
CA (1) CA2265917C (enExample)
DE (1) DE69720481T2 (enExample)
DK (1) DK0928335T3 (enExample)
ES (1) ES2190541T3 (enExample)
PT (1) PT928335E (enExample)
WO (1) WO1998011211A2 (enExample)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999058118A3 (en) * 1998-05-14 2000-01-13 Cpg Immunopharmaceuticals Gmbh METHODS FOR REGULATING HEMATOPOIESIS USING CpG-OLIGONUCLEOTIDES
WO2000014262A3 (en) * 1998-09-09 2000-06-29 Genzyme Corp Methylation of plasmid vectors
WO2001012804A3 (en) * 1999-08-13 2001-09-07 Hybridon Inc MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES
EP1168919A4 (en) * 1999-04-06 2002-03-06 Univ East Carolina ANTISENSE OLIGONUCLEOTIDES WITH LOW ADENOSINE CONTENT, COMPOSITIONS, KIT AND TREATMENT METHOD FOR AIR DISORDERS ASSOCIATED WITH BRONCHOCONSTRICTION, PITAL INFLAMMATION, ALLERGIES AND SURFACTANT DEPLOYMENT
EP1102786A4 (en) * 1998-08-03 2002-03-06 Univ East Carolina AGENT COMPRISING ANTISENSE OLIGONUCLEOTIDES WITH LOW ADENOSINE CONTENT, COMPOSITION, KIT AND TREATMENTS
WO2001040478A3 (en) * 1999-12-06 2002-05-10 Pasteur Institut Isolated polynucleotides having a reduced or an increased content of epigenetic control motifs and uses thereof
US6825174B2 (en) 1995-06-07 2004-11-30 East Carolina University Composition, formulations & method for prevention & treatment of diseases and conditions associated with bronchoconstriction, allergy(ies) & inflammation
EP1496121A3 (en) * 1999-08-13 2005-02-09 Hybridon, Inc. Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides
US7034007B1 (en) 1995-06-07 2006-04-25 East Carolina University Low adenosine anti-sense oligonucleotide, compositions, kit & method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) & surfactant depletion
US7282476B2 (en) 2001-08-24 2007-10-16 University Of Victoria Innovation And Development Corporation Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer
US7514414B2 (en) 2001-09-24 2009-04-07 The United States Of America As Represented By The Department Of Health And Human Services Suppressors of CpG oligonucleotides and methods of use
US7514415B2 (en) 2002-08-01 2009-04-07 The United States Of America As Represented By The Department Of Health And Human Services Method of treating inflammatory arthropathies with suppressors of CpG oligonucleotides
US7615539B2 (en) 2003-09-25 2009-11-10 Coley Pharmaceutical Group, Inc. Nucleic acid-lipophilic conjugates
US7723500B2 (en) 1994-07-15 2010-05-25 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US7919477B2 (en) 2000-01-14 2011-04-05 The United States Of America As Represented By The Department Of Health And Human Services Multiple CpG oligodeoxynucleotides and their use to induce an immune response
US8043622B2 (en) 2002-10-08 2011-10-25 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides
US8188254B2 (en) 2003-10-30 2012-05-29 Coley Pharmaceutical Gmbh C-class oligonucleotide analogs with enhanced immunostimulatory potency
US8222225B2 (en) 2008-05-21 2012-07-17 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating pneumoconiosis with oligodeoxynucleotides
US8283328B2 (en) 2002-08-19 2012-10-09 Coley Pharmaceutical Group, Inc. Immunostimulatory nucleic acids
US8580268B2 (en) 2006-09-27 2013-11-12 Coley Pharmaceutical Gmbh CpG oligonucleotide analogs containing hydrophobic T analogs with enhanced immunostimulatory activity
US8895521B2 (en) 2004-05-06 2014-11-25 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Methods and compositions for the treatment of uveitis
US8916161B2 (en) 2005-06-14 2014-12-23 Sophiris Bio Inc. Method of treating or preventing benign prostatic hyperplasia using modified pore-forming proteins
US9809824B2 (en) 2004-12-13 2017-11-07 The United States Of America, Represented By The Secretary, Department Of Health And Human Services CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2711670B1 (fr) 1993-10-22 1996-01-12 Pasteur Institut Vecteur nucléotidique, composition le contenant et vaccin pour l'immunisation à l'encontre d'une hépatite.
US6727230B1 (en) * 1994-03-25 2004-04-27 Coley Pharmaceutical Group, Inc. Immune stimulation by phosphorothioate oligonucleotide analogs
US6592877B1 (en) * 1995-09-01 2003-07-15 Corixa Corporation Compounds and methods for immunotherapy and diagnosis of tuberculosis
US6290969B1 (en) * 1995-09-01 2001-09-18 Corixa Corporation Compounds and methods for immunotherapy and diagnosis of tuberculosis
US6458366B1 (en) 1995-09-01 2002-10-01 Corixa Corporation Compounds and methods for diagnosis of tuberculosis
US20020147143A1 (en) 1998-03-18 2002-10-10 Corixa Corporation Compositions and methods for the therapy and diagnosis of lung cancer
US6238921B1 (en) * 1998-03-26 2001-05-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of human mdm2 expression
US20030235557A1 (en) 1998-09-30 2003-12-25 Corixa Corporation Compositions and methods for WT1 specific immunotherapy
US6214986B1 (en) * 1998-10-07 2001-04-10 Isis Pharmaceuticals, Inc. Antisense modulation of bcl-x expression
US6172216B1 (en) * 1998-10-07 2001-01-09 Isis Pharmaceuticals Inc. Antisense modulation of BCL-X expression
US5962673A (en) * 1998-11-20 1999-10-05 Isis Pharmaceuticals Inc. Antisense modulation of inhibitor-kappa B kinase-alpha expression
US5959097A (en) * 1998-11-20 1999-09-28 Isis Pharmaceuticals, Inc. Antisense modulation of MEK2 expression
US5977341A (en) * 1998-11-20 1999-11-02 Isis Pharmaceuticals Inc. Antisense modulation of inhibitor-kappa B kinase-beta expression
US5981732A (en) * 1998-12-04 1999-11-09 Isis Pharmaceuticals Inc. Antisense modulation of G-alpha-13 expression
US6140124A (en) * 1999-04-06 2000-10-31 Isis Pharmaceuticals Inc. Antisense modulation of P38 mitogen activated protein kinase expression
US20040171566A1 (en) * 1999-04-06 2004-09-02 Monia Brett P. Antisense modulation of p38 mitogen activated protein kinase expression
US8143386B2 (en) * 1999-04-07 2012-03-27 Corixa Corporation Fusion proteins of mycobacterium tuberculosis antigens and their uses
US6013788A (en) * 1999-04-09 2000-01-11 Isis Pharmaceuticals Inc. Antisense modulation of Smad3 expression
US6046321A (en) * 1999-04-09 2000-04-04 Isis Pharmaceuticals Inc. Antisense modulation of G-alpha-i1 expression
DE19935756A1 (de) * 1999-07-27 2001-02-08 Mologen Forschungs Entwicklung Kovalent geschlossenes Nukleinsäuremolekül zur Immunstimulation
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WO2001062893A2 (en) 2000-02-25 2001-08-30 Corixa Corporation Compounds and methods for diagnosis and immunotherapy of tuberculosis
US20040002068A1 (en) 2000-03-01 2004-01-01 Corixa Corporation Compositions and methods for the detection, diagnosis and therapy of hematological malignancies
US20040006036A1 (en) * 2000-04-12 2004-01-08 Gmr, A Delaware Corporation Silencing transcription by methylation
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WO2002069369A2 (en) * 2000-12-08 2002-09-06 Coley Pharmaceutical Gmbh Cpg-like nucleic acids and methods of use thereof
GB0105360D0 (en) * 2001-03-03 2001-04-18 Glaxo Group Ltd Chimaeric immunogens
US7105495B2 (en) * 2001-04-30 2006-09-12 Idera Pharmaceuticals, Inc. Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides
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US7276489B2 (en) * 2002-10-24 2007-10-02 Idera Pharmaceuticals, Inc. Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends
WO2003035836A2 (en) * 2001-10-24 2003-05-01 Hybridon Inc. Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends
SI1456380T1 (sl) * 2001-11-02 2012-11-30 Giuliani Int Ltd Smad inhibitorji za zdravljenje cns bolezni
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AU2002366710A1 (en) 2001-12-20 2003-07-09 The Government Of The United States Of America As Represented By The Secretary Of The Department Of USE OF CpG OLIGODEOXYNUCLEOTIDES TO INDUCE ANGIOGENESIS
AU2003203079B9 (en) * 2002-02-04 2009-01-15 Oncothyreon Inc. Immunostimulatory, covalently lipidated oligonucleotides
AU2003213118A1 (en) * 2002-02-15 2003-09-09 Corixa Corporation Fusion proteins of mycobacterium tuberculosis
SI1589934T1 (sl) 2003-01-06 2016-02-29 Corixa Corporation Corporation Service Company Določene aminoalkil glukozaminid fosfat spojine in njih uporaba
US7960522B2 (en) 2003-01-06 2011-06-14 Corixa Corporation Certain aminoalkyl glucosaminide phosphate compounds and their use
US7354907B2 (en) 2003-02-07 2008-04-08 Idera Pharmaceuticals, Inc. Short immunomodulatory oligonucleotides
ITRM20030149A1 (it) 2003-04-02 2004-10-03 Giuliani Spa Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico
EP1608403A2 (en) * 2003-04-02 2005-12-28 Coley Pharmaceutical Group, Ltd. Immunostimulatory nucleic acid oil-in-water formulations for topical application
AU2005285513B2 (en) 2004-05-25 2011-02-24 Oregon Health And Science University SIV and HIV vaccination using RhCMV- and HCMV-based vaccine vectors
GB0427131D0 (en) * 2004-12-10 2005-01-12 Glaxosmithkline Biolog Sa Novel combination
CN101184504A (zh) 2005-03-31 2008-05-21 葛兰素史密丝克莱恩生物有限公司 针对衣原体感染的疫苗
PT2426141E (pt) 2005-04-29 2014-11-25 Glaxosmithkline Biolog Sa Método para prevenção ou tratamento de uma infecção por m. tuberculosis
WO2008124647A2 (en) 2007-04-04 2008-10-16 Infectious Disease Research Institute Immunogenic compositions comprising mycobacterium tuberculosis polypeptides and fusions thereof
US9452209B2 (en) * 2007-04-20 2016-09-27 Glaxosmithkline Biologicals Sa Influenza vaccine
ES2725450T3 (es) 2007-07-02 2019-09-24 Etubics Corp Métodos y composiciones para la producción de un vector adenoviral para su uso en vacunaciones múltiples
US8236318B2 (en) 2007-11-07 2012-08-07 Celldex Therapeutics Inc. Antibodies that bind human dendritic and epithelial cell 205 (DEC-205)
US8563002B2 (en) 2007-12-24 2013-10-22 Glaxosmithkline Biologicals, S.A. Recombinant RSV antigens
MX2011005915A (es) 2008-12-03 2011-08-17 Proyecto Biomedicina Cima Sl Uso de modulinas solubles en fenol para el desarrollo de vacunas.
PL2445526T3 (pl) 2009-06-24 2017-08-31 Glaxosmithkline Biologicals S.A. Rekombinowane antygeny rsv
SG176807A1 (en) 2009-06-24 2012-01-30 Id Biomedical Corp Quebec Vaccine
EP4183412B1 (en) 2009-07-15 2024-08-14 GlaxoSmithKline Biologicals SA Rsv f protein compositions and methods for making same
GB0919117D0 (en) 2009-10-30 2009-12-16 Glaxosmithkline Biolog Sa Process
WO2011101332A1 (en) 2010-02-16 2011-08-25 Proyecto De Biomedicina Cima, S.L. Compositions based on the fibronectin extracellular domain a for the treatment of melanoma
JP6002659B2 (ja) 2010-04-13 2016-10-05 セルデックス・セラピューティクス・インコーポレイテッド ヒトｃｄ２７に結合する抗体およびその使用
US20130345079A1 (en) 2010-10-27 2013-12-26 Infectious Disease Research Institute Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity
EP2637687B1 (en) 2010-11-08 2021-01-06 Infectious Disease Research Institute Vaccines comprising non-specific nucleoside hydrolase and sterol 24-c-methyltransferase (smt) polypeptides for the treatment and diagnosis of leishmaniasis
EP2505640A1 (en) 2011-03-29 2012-10-03 Neo Virnatech, S.L. Vaccine compositions for birnavirus-borne diseases
GB201106357D0 (en) 2011-04-14 2011-06-01 Pessi Antonello Composition and uses thereof
RS56748B1 (sr) 2011-05-13 2018-03-30 Glaxosmithkline Biologicals Sa Pre-fuzioni rsv f antigeni
JP2014527398A (ja) 2011-06-21 2014-10-16 オンコファクター コーポレイション がんの療法および診断のための組成物および方法
EP2666785A1 (en) 2012-05-23 2013-11-27 Affiris AG Complement component C5a-based vaccine
EP4299138A3 (en) 2012-08-03 2024-08-14 Access to Advanced Health Institute Compositions and methods for treating an active mycobacterium tuberculosis infection
SG11201500573RA (en) 2012-08-06 2015-02-27 Glaxosmithkline Biolog Sa Method for eliciting in infants an immune response against rsv and b. pertussis
US20140037680A1 (en) 2012-08-06 2014-02-06 Glaxosmithkline Biologicals, S.A. Novel method
US9605276B2 (en) 2012-08-24 2017-03-28 Etubics Corporation Replication defective adenovirus vector in vaccination
EP2703483A1 (en) 2012-08-29 2014-03-05 Affiris AG PCSK9 peptide vaccine
EP4421177A3 (en) 2013-03-13 2024-12-18 The United States of America, as represented by the Secretary, Department of Health and Human Services Prefusion rsv f proteins and their use
US10058603B2 (en) 2013-03-15 2018-08-28 Glaxosmithkline Biologicals S.A. Vaccine
EP2978447B1 (en) 2013-03-28 2019-05-08 Infectious Disease Research Institute Vaccines comprising leishmania polypeptides for the treatment and diagnosis of leishmaniasis
SG11201600709TA (en) 2013-08-05 2016-02-26 Glaxosmithkline Biolog Sa Combination immunogenic compositions
EP2952893A1 (en) 2014-06-04 2015-12-09 Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) Method for detecting antibody-secreting B cells specific for HLA
EP3154576A1 (en) 2014-06-13 2017-04-19 GlaxoSmithKline Biologicals S.A. Immunogenic combinations
AR102548A1 (es) 2014-11-07 2017-03-08 Takeda Vaccines Inc Vacunas contra la enfermedad de manos, pies y boca y métodos de fabricación y uso
AR102547A1 (es) 2014-11-07 2017-03-08 Takeda Vaccines Inc Vacunas contra la enfermedad de manos, pies y boca y métodos de fabricación y su uso
EP3233912B1 (en) 2014-12-19 2021-05-19 Regenesance B.V. Antibodies that bind human c6 and uses thereof
AU2016205215B2 (en) 2015-01-09 2021-03-11 Etubics Corporation Methods and compositions for combination immunotherapy
WO2016140702A1 (en) 2015-03-03 2016-09-09 The United States Of America, As Represented By The Secretary, Department Of Health & Human Serivces Display platform from bacterial spore coat proteins
WO2016145085A2 (en) 2015-03-09 2016-09-15 Celldex Therapeutics, Inc. Cd27 agonists
US11149087B2 (en) 2015-04-20 2021-10-19 Etubics Corporation Methods and compositions for combination immunotherapy
US10682314B2 (en) 2015-05-26 2020-06-16 Ohio State Innovation Foundation Nanoparticle based vaccine strategy against swine influenza virus
LU92821B1 (en) 2015-09-09 2017-03-20 Mologen Ag Combination comprising immunostimulatory oligonucleotides
GB2542425A (en) 2015-09-21 2017-03-22 Mologen Ag Means for the treatment of HIV
BR112018071307A2 (pt) 2016-04-18 2019-02-26 Celldex Therapeutics, Inc. anticorpos agonistas que ligam cd40 humana e usos dos mesmos
EP3458088A2 (en) 2016-05-21 2019-03-27 Infectious Disease Research Institute Compositions and methods for treating secondary tuberculosis and nontuberculous mycobacterium infections
EP3735984A1 (en) 2016-05-27 2020-11-11 Etubics Corporation Neoepitope vaccine compositions and methods of use thereof
WO2018053294A1 (en) 2016-09-16 2018-03-22 Infectious Disease Research Institute Vaccines comprising mycobacterium leprae polypeptides for the prevention, treatment, and diagnosis of leprosy
WO2018109220A2 (en) 2016-12-16 2018-06-21 Institute For Research In Biomedicine Novel recombinant prefusion rsv f proteins and uses thereof
WO2018162450A1 (en) 2017-03-06 2018-09-13 Fundación Para La Investigación Médica Aplicada New inmunostimulatory compositions comprising an entity of cold inducible rna-binding protein with an antigen for the activation of dendritic cells
EP3612562A2 (en) 2017-04-19 2020-02-26 Institute for Research in Biomedicine Plasmodium sporozoite npdp peptides as vaccine and target novel malaria vaccines and antibodies binding to
AU2018285694B2 (en) 2017-06-15 2025-04-10 Access To Advanced Health Institute Nanostructured lipid carriers and stable emulsions and uses thereof
US11123415B2 (en) 2017-08-16 2021-09-21 Ohio State Innovation Foundation Nanoparticle compositions for Salmonella vaccines
MY202505A (en) 2017-11-03 2024-05-01 Takeda Vaccines Inc Zika vaccines and immunogenic compositions, and methods of using the same
EP3743102A1 (en) 2018-01-26 2020-12-02 Nantcell, Inc. Compositions and methods for combination cancer vaccine and immunologic adjuvant therapy
WO2019183570A1 (en) 2018-03-22 2019-09-26 Board Of Regents, The University Of Texas System Soluble interleukin-7 receptor (sil7r) molulating therapy to treat autoimmune diseases and cancer
KR20210011919A (ko) 2018-04-17 2021-02-02 셀덱스 쎄라퓨틱스, 인크. 항-cd27 항체 및 항-pd-l1 항체 및 이중특이적 작제물
US20230310323A1 (en) 2020-09-04 2023-10-05 Access To Advanced Health Institute Co-lyophilized rna and nanostructured lipid carrier
CN117545773A (zh) 2021-04-09 2024-02-09 塞德斯医疗公司 抗ilt4的抗体、双特异性抗ilt4/pd-l1抗体及其用途
WO2023077521A1 (en) 2021-11-08 2023-05-11 Celldex Therapeutics, Inc Anti-ilt4 and anti-pd-1 bispecific constructs
US20250082745A1 (en) 2021-12-13 2025-03-13 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Bacteriophage lambda-vaccine system
WO2024052882A1 (en) 2022-09-09 2024-03-14 Access To Advanced Health Institute Immunogenic vaccine composition incorporating a saponin
KR20250167153A (ko) 2023-03-03 2025-11-28 셀덱스 쎄라퓨틱스, 인크. 항-줄기 세포 인자(scf) 및 항-흉선 기질 림포포이에틴(tslp) 항체, 및 이중특이적 구축물

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4806463A (en) * 1986-05-23 1989-02-21 Worcester Foundation For Experimental Biology Inhibition of HTLV-III by exogenous oligonucleotides
US5194428A (en) * 1986-05-23 1993-03-16 Worcester Foundation For Experimental Biology Inhibition of influenza virus replication by oligonucleotide phosphorothioates
US5149797A (en) * 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
DE4200433A1 (de) * 1992-01-10 1993-07-15 Otto Hofstetter Verfahren zur herstellung von stabilen fluessigen parfuemrohstoffmischungen mit hohem feststoffgehalt
US5652355A (en) * 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
KR960702518A (ko) * 1993-05-17 1996-04-27 린다 에스, 스티븐슨 Hiv 감염 및 aids에 대한 리보자임 유전자 치료(ribozyme gene therapy for hiv infection and aids)
CN1136327A (zh) * 1993-09-28 1996-11-20 综合医院公司 用反义寡核苷酸调节神经生长并使β/A4淀粉样肽诱导的形态逆转
AU713040B2 (en) * 1994-07-15 1999-11-18 University Of Iowa Research Foundation, The Immunomodulatory oligonucleotides
AU4514696A (en) * 1994-12-22 1996-07-10 Hybridon, Inc. Synthesis of stereospecific oligonucleotide phosphorothioates

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7723500B2 (en) 1994-07-15 2010-05-25 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US8158592B2 (en) 1994-07-15 2012-04-17 Coley Pharmaceutical Group, Inc. Immunostimulatory nucleic acid molecules
US8058249B2 (en) 1994-07-15 2011-11-15 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US6825174B2 (en) 1995-06-07 2004-11-30 East Carolina University Composition, formulations & method for prevention & treatment of diseases and conditions associated with bronchoconstriction, allergy(ies) & inflammation
US7034007B1 (en) 1995-06-07 2006-04-25 East Carolina University Low adenosine anti-sense oligonucleotide, compositions, kit & method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) & surfactant depletion
WO1999058118A3 (en) * 1998-05-14 2000-01-13 Cpg Immunopharmaceuticals Gmbh METHODS FOR REGULATING HEMATOPOIESIS USING CpG-OLIGONUCLEOTIDES
EP1674574A1 (en) * 1998-05-14 2006-06-28 Coley Pharmaceutical GmbH Methods for Regulating Hematopoiesis using CpG-Oligonucleotides
EP1102786A4 (en) * 1998-08-03 2002-03-06 Univ East Carolina AGENT COMPRISING ANTISENSE OLIGONUCLEOTIDES WITH LOW ADENOSINE CONTENT, COMPOSITION, KIT AND TREATMENTS
WO2000014262A3 (en) * 1998-09-09 2000-06-29 Genzyme Corp Methylation of plasmid vectors
EP1832657A1 (en) * 1998-09-09 2007-09-12 Genzyme Corporation Methylation of plasmid vectors
EP1168919A4 (en) * 1999-04-06 2002-03-06 Univ East Carolina ANTISENSE OLIGONUCLEOTIDES WITH LOW ADENOSINE CONTENT, COMPOSITIONS, KIT AND TREATMENT METHOD FOR AIR DISORDERS ASSOCIATED WITH BRONCHOCONSTRICTION, PITAL INFLAMMATION, ALLERGIES AND SURFACTANT DEPLOYMENT
EP2314693A3 (en) * 1999-08-13 2012-11-28 Idera Pharmaceuticals, Inc. Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides
WO2001012804A3 (en) * 1999-08-13 2001-09-07 Hybridon Inc MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES
EP1496121A3 (en) * 1999-08-13 2005-02-09 Hybridon, Inc. Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides
WO2001040478A3 (en) * 1999-12-06 2002-05-10 Pasteur Institut Isolated polynucleotides having a reduced or an increased content of epigenetic control motifs and uses thereof
US7919477B2 (en) 2000-01-14 2011-04-05 The United States Of America As Represented By The Department Of Health And Human Services Multiple CpG oligodeoxynucleotides and their use to induce an immune response
US8232259B2 (en) 2000-01-14 2012-07-31 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Multiple CpG oligodeoxynucleotide and their use to induce an immune response
US7282476B2 (en) 2001-08-24 2007-10-16 University Of Victoria Innovation And Development Corporation Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer
US7745395B2 (en) 2001-08-24 2010-06-29 University of Victoria Innovatiion and Development Corporation Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer
US7838266B2 (en) 2001-08-24 2010-11-23 University Of Victoria Innovation And Development Corporation Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer
US8227438B2 (en) 2001-09-24 2012-07-24 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Suppressors of CpG oligonucleotides and methods of use
US9163244B2 (en) 2001-09-24 2015-10-20 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Suppressors of CpG oligonucleotides and methods of use
US8580944B2 (en) 2001-09-24 2013-11-12 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Suppressors of CpG oligonucleotides and methods of use
US7514414B2 (en) 2001-09-24 2009-04-07 The United States Of America As Represented By The Department Of Health And Human Services Suppressors of CpG oligonucleotides and methods of use
US7951786B2 (en) 2002-08-01 2011-05-31 The United States Of America As Represented By The Department Of Health And Human Services Method of treating inflammatory arthropathies with suppressors of CpG oligonucleotides
US8557789B2 (en) 2002-08-01 2013-10-15 The United States of America as represented by the Secretary of the Development of Health and Human Services Method of treating inflammatory arthropathies with supressors of CPG oligonucleotides
US7514415B2 (en) 2002-08-01 2009-04-07 The United States Of America As Represented By The Department Of Health And Human Services Method of treating inflammatory arthropathies with suppressors of CpG oligonucleotides
US8288359B2 (en) 2002-08-01 2012-10-16 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating inflammatory arthropathies with suppressors of CpG oligonucleotides
US8283328B2 (en) 2002-08-19 2012-10-09 Coley Pharmaceutical Group, Inc. Immunostimulatory nucleic acids
US8304396B2 (en) 2002-08-19 2012-11-06 Coley Pharmaceutical Group, Inc. Immunostimulatory nucleic acids
US9006203B2 (en) 2002-10-08 2015-04-14 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of reducing inflammatory infiltration in subjects with inflammatory lung disease
US8501188B2 (en) 2002-10-08 2013-08-06 The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides
US8043622B2 (en) 2002-10-08 2011-10-25 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides
US7615539B2 (en) 2003-09-25 2009-11-10 Coley Pharmaceutical Group, Inc. Nucleic acid-lipophilic conjugates
US8188254B2 (en) 2003-10-30 2012-05-29 Coley Pharmaceutical Gmbh C-class oligonucleotide analogs with enhanced immunostimulatory potency
US8895521B2 (en) 2004-05-06 2014-11-25 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Methods and compositions for the treatment of uveitis
US9809824B2 (en) 2004-12-13 2017-11-07 The United States Of America, Represented By The Secretary, Department Of Health And Human Services CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods
US8916161B2 (en) 2005-06-14 2014-12-23 Sophiris Bio Inc. Method of treating or preventing benign prostatic hyperplasia using modified pore-forming proteins
US9950029B2 (en) 2005-06-14 2018-04-24 Sophiris Bio Inc. Method of treating or preventing benign prostatic hyperplasia using modified pore-forming proteins
US8580268B2 (en) 2006-09-27 2013-11-12 Coley Pharmaceutical Gmbh CpG oligonucleotide analogs containing hydrophobic T analogs with enhanced immunostimulatory activity
US10260071B2 (en) 2006-09-27 2019-04-16 Coley Pharmaceutical Gmbh CpG oligonucleotide analogs containing hydrophobic T analogs with enhanced immunostimulatory activity
US8222225B2 (en) 2008-05-21 2012-07-17 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating pneumoconiosis with oligodeoxynucleotides

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