WO2011128374A1 - Conjugués insuline-arnsi - Google Patents

Conjugués insuline-arnsi Download PDF

Info

Publication number
WO2011128374A1
WO2011128374A1 PCT/EP2011/055823 EP2011055823W WO2011128374A1 WO 2011128374 A1 WO2011128374 A1 WO 2011128374A1 EP 2011055823 W EP2011055823 W EP 2011055823W WO 2011128374 A1 WO2011128374 A1 WO 2011128374A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
cycloalkyl
aryl
heterocyclyl
heteroaryl
Prior art date
Application number
PCT/EP2011/055823
Other languages
English (en)
Inventor
Werner Kramer
David William Will
Marcus Hermann Korn
Bodo Brunner
Original Assignee
Sanofi
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 Sanofi filed Critical Sanofi
Publication of WO2011128374A1 publication Critical patent/WO2011128374A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne généralement des composés thérapeutiques et des procédés utiles pour traiter une maladie chez des humains. Spécifiquement, la présente invention concerne des procédés et des réactifs utiles pour traiter des humains souffrant de maladies métaboliques. Spécifiquement, la présente invention concerne des conjugués covalents d'insuline et d'analogues avec des dérivés d'acide nucléique qui sont capables de moduler l'expression génique. De plus, cette invention concerne l'utilisation de telles insulines conjuguées pour le traitement de maladies métaboliques, comprenant le diabète sucré.
PCT/EP2011/055823 2010-04-14 2011-04-13 Conjugués insuline-arnsi WO2011128374A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP10305388.0 2010-04-14
EP10305388 2010-04-14
US38716210P 2010-09-28 2010-09-28
US61/387,162 2010-09-28

Publications (1)

Publication Number Publication Date
WO2011128374A1 true WO2011128374A1 (fr) 2011-10-20

Family

ID=42633135

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/055823 WO2011128374A1 (fr) 2010-04-14 2011-04-13 Conjugués insuline-arnsi

Country Status (4)

Country Link
AR (1) AR080884A1 (fr)
TW (1) TW201141513A (fr)
UY (1) UY33326A (fr)
WO (1) WO2011128374A1 (fr)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9345750B2 (en) 2010-05-19 2016-05-24 Sanofi Long-acting formulations of insulin
US9364519B2 (en) 2011-09-01 2016-06-14 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition for use in the treatment of a neurodegenerative disease
US9408893B2 (en) 2011-08-29 2016-08-09 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for use in glycemic control in diabetes type 2 patients
US9526764B2 (en) 2008-10-17 2016-12-27 Sanofi-Aventis Deutschland Gmbh Combination of an insulin and a GLP-1-agonist
US9707176B2 (en) 2009-11-13 2017-07-18 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1 agonist and methionine
US9821032B2 (en) 2011-05-13 2017-11-21 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
US9908908B2 (en) 2012-08-30 2018-03-06 Jiangsu Hansoh Pharmaceutical Co., Ltd. Tenofovir prodrug and pharmaceutical uses thereof
US9950039B2 (en) 2014-12-12 2018-04-24 Sanofi-Aventis Deutschland Gmbh Insulin glargine/lixisenatide fixed ratio formulation
US9981013B2 (en) 2010-08-30 2018-05-29 Sanofi-Aventis Deutschland Gmbh Use of AVE0010 for the treatment of diabetes mellitus type 2
US10029011B2 (en) 2009-11-13 2018-07-24 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1 agonist, an insulin and methionine
US10092513B2 (en) 2013-04-03 2018-10-09 Sanofi Treatment of diabetes mellitus by long-acting formulations of insulins
US10159713B2 (en) 2015-03-18 2018-12-25 Sanofi-Aventis Deutschland Gmbh Treatment of type 2 diabetes mellitus patients
US10434147B2 (en) 2015-03-13 2019-10-08 Sanofi-Aventis Deutschland Gmbh Treatment type 2 diabetes mellitus patients
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
US11981703B2 (en) 2017-08-17 2024-05-14 Sirius Therapeutics, Inc. Polynucleotide constructs

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0254516A2 (fr) 1986-07-21 1988-01-27 Novo Nordisk A/S Peptides
EP0280534A2 (fr) 1987-02-25 1988-08-31 Novo Nordisk A/S Nouveaux dérivés de l'insuline
US5618913A (en) 1985-08-30 1997-04-08 Novo Nordisk A/S Insulin analogues
US5750497A (en) 1993-09-17 1998-05-12 Novo Nordisk A/S Acylated insulin
US6011007A (en) 1993-09-17 2000-01-04 Novo Nordisk A/S Acylated insulin
WO2003099227A2 (fr) 2002-05-23 2003-12-04 Ceptyr, Inc. Modulation de la transduction de signaux ptp1b par l'interference d'arn
US20040147027A1 (en) 2003-01-28 2004-07-29 Troy Carol M. Complex for facilitating delivery of dsRNA into a cell and uses thereof
WO2005002515A2 (fr) * 2003-06-20 2005-01-13 Biomarin Pharmaceutical Inc. Administration de composes therapeutiques au cerveau et a d'autres tissus
US20060019913A1 (en) 2001-05-18 2006-01-26 Sirna Therapeutics, Inc. RNA interference mediated inhibtion of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
WO2006037126A2 (fr) 2004-09-27 2006-04-06 Nastech Pharmaceutical Company Inc. Methode de traitement de maladie inflammatoire par acide ribonucleique bicatenaire
WO2006079641A2 (fr) 2005-01-27 2006-08-03 Novo Nordisk A/S Derives d'insuline conjugues avec des polymeres ramifies structurellement bien definis
WO2007007345A1 (fr) 2005-07-08 2007-01-18 Biocon Limited Préparation de conjugués d'insuline
WO2007043059A1 (fr) 2005-10-13 2007-04-19 Biocon Limited Procédé de synthèse de conjugués d'insuline
WO2007056153A2 (fr) 2005-11-04 2007-05-18 Nastech Pharmaceutical Company Inc. Conjugues de peptide-arn substrat dicer utilises comme excipients d'administration pour arnsi
WO2008109068A2 (fr) 2007-03-05 2008-09-12 Syracuse University Conjugué d'insuline et de vitamine b12 pour administration orale

Patent Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5618913A (en) 1985-08-30 1997-04-08 Novo Nordisk A/S Insulin analogues
EP0254516A2 (fr) 1986-07-21 1988-01-27 Novo Nordisk A/S Peptides
EP0280534A2 (fr) 1987-02-25 1988-08-31 Novo Nordisk A/S Nouveaux dérivés de l'insuline
US5750497A (en) 1993-09-17 1998-05-12 Novo Nordisk A/S Acylated insulin
US6011007A (en) 1993-09-17 2000-01-04 Novo Nordisk A/S Acylated insulin
US20060025361A1 (en) 2001-05-18 2006-02-02 Sirna Therapeutics, Inc. RNA interference mediated inhibition of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US20060019913A1 (en) 2001-05-18 2006-01-26 Sirna Therapeutics, Inc. RNA interference mediated inhibtion of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
WO2004016735A2 (fr) 2002-05-23 2004-02-26 Ceptyr, Inc. Modulation de la transduction du signal biologique par interference arn
US20040077574A1 (en) 2002-05-23 2004-04-22 Ceptyr, Inc. Modulation of biological signal transduction by RNA interference
US20040009946A1 (en) 2002-05-23 2004-01-15 Ceptyr, Inc. Modulation of PTP1B expression and signal transduction by RNA interference
WO2003099227A2 (fr) 2002-05-23 2003-12-04 Ceptyr, Inc. Modulation de la transduction de signaux ptp1b par l'interference d'arn
US20040147027A1 (en) 2003-01-28 2004-07-29 Troy Carol M. Complex for facilitating delivery of dsRNA into a cell and uses thereof
WO2005002515A2 (fr) * 2003-06-20 2005-01-13 Biomarin Pharmaceutical Inc. Administration de composes therapeutiques au cerveau et a d'autres tissus
WO2006037126A2 (fr) 2004-09-27 2006-04-06 Nastech Pharmaceutical Company Inc. Methode de traitement de maladie inflammatoire par acide ribonucleique bicatenaire
WO2006079641A2 (fr) 2005-01-27 2006-08-03 Novo Nordisk A/S Derives d'insuline conjugues avec des polymeres ramifies structurellement bien definis
WO2007007345A1 (fr) 2005-07-08 2007-01-18 Biocon Limited Préparation de conjugués d'insuline
WO2007043059A1 (fr) 2005-10-13 2007-04-19 Biocon Limited Procédé de synthèse de conjugués d'insuline
WO2007056153A2 (fr) 2005-11-04 2007-05-18 Nastech Pharmaceutical Company Inc. Conjugues de peptide-arn substrat dicer utilises comme excipients d'administration pour arnsi
WO2008109068A2 (fr) 2007-03-05 2008-09-12 Syracuse University Conjugué d'insuline et de vitamine b12 pour administration orale

Non-Patent Citations (93)

* Cited by examiner, † Cited by third party
Title
"Hermanson, G.T. Bioconjugate Techniques", 2008, ACADEMIC PRESS, pages: 169 - 211
"The Diabetes Control and Complications Trial Research Group", N. ENGL. J. MED., vol. 329, 1993, pages 977 - 986
*VICENATI ET AL., INT J OBES, vol. 26, 2002, pages 905 - 911
AAGAARD, L, ROSSI, J.J., ADVANCED DRUG DELIVERY REVIEWS, vol. 59, 2007, pages 75 - 86
AIGNER, A, JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, vol. 71659, 2006, pages 1 - 15
AKHTAR, S., BENTER, I.F., J. CLIN. INVEST., vol. 117, 2007, pages 3623 - 3632
ALLERSON, C.R. ET AL., J. MED. CHEM., vol. 48, 2005, pages 901 - 904
AMARZGUIOUI, M., NUCLEIC ACIDS RESEARCH, vol. 31, no. 2, 2003, pages 589 - 595
AMARZGUIOUI, M., PRYDZ, H., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 316, 2004, pages 1050 - 1058
ANGEW. CHEM. INT. ED. ENGL., vol. 46, 2007, pages 6985 - 6994
BEAUCAGE, S., CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT, vol. 11, no. 2, 2008, pages 203 - 216
BIOL. CHEM. HOPPE SEYLER, 1986, pages 135 - 140
BRAASCH, D.A. ET AL., BIOCHEMISTRY, vol. 42, 2003, pages 7967 - 7975
BUMCROT, D. ET AL., NATURE CHEMICAL BIOLOGY, vol. 2, no. 12, 2006, pages 711 - 719
CANADIAN JOURNAL OF BIOCHEMISTRY, vol. 57, no. 6, 1979, pages 489 - 496
CARPENTIER, J.-L., DIABETOLOGIA, vol. 2, 1994, pages 117 - 124
CESARONE GREGORY ET AL: "Insulin receptor substrate 1 knockdown in human MCF7 ER+ breast cancer cells by nuclease-resistant IRS1 siRNA conjugated to a disulfide-bridged D-Peptide analogue of insulin-like growth factor 1", BIOCONJUGATE CHEMISTRY, vol. 18, 9 October 2007 (2007-10-09), pages 1831 - 1840, XP002598719 *
CESARONE, G. ET AL., BIOCONJUGATE CHEM., vol. 18, 2007, pages 1831 - 1840
CHEM. BER., vol. 108, 1975, pages 2758 - 2763
CHIU ET AL., MOLECULAR CELL, vol. 10, 2002, pages 549 - 561
COREY, D.A., J. CLIN. INVEST., vol. 117, 2007, pages 3615 - 3622
CZAUDERNA, F., NUCLEIC ACIDS RESEARCH, vol. 31, no. 11, 2003, pages 2705 - 2716
DE PAULA, D. ET AL., RNA, vol. 13, 2007, pages 431 - 456
DE ROSA, G., MOLECULES, vol. 14, 2009, pages 2801 - 2823
EBERLE, F. ET AL., THE JOURNAL OF IMMUNOLOGY, vol. 180, 2008, pages 3229 - 3237
ELBASHIR, S.M. ET AL., NATURE, vol. 411, 2001, pages 494 - 498
ELCHEBLY, M. ET AL., SCIENCE, vol. 283, no. 5407, 1999, pages 1544 - 1548
FIRE, A. ET AL., NATURE, vol. 391, 1998, pages 806 - 811
FIRE, A., ANGEW. CHEM. INT. ED. ENGL., vol. 46, 2007, pages 6966 - 6984
FOTI, M. ET AL., NOVARTIS FOUNDATION SYMPOSIUM, vol. 262, 2004, pages 125 - 147
GAIT, M.J., CELL. MOL. LIFE SCI., vol. 60, 2003, pages 844 - 853
GERSHONOV, E. ET AL., JOURNAL OF MEDICINAL CHEMISTRY, vol. 43, no. 13, 2000, pages 2530 - 2537
GHILDIYAL, M., ZAMORE, P.D., NATURE REVIEWS GENETICS, vol. 10, 2009, pages 94 - 108
GUPTA, B. ET AL., ADV. DRUG DELIV. REV., vol. 57, 2005, pages 637 - 651
HAMILTON ET AL., SCIENCE, vol. 286, 1999, pages 950 - 951
HERMANSON, G.T.: "Bioconjugate Techniques", 2008, ACADEMIC PRESS
HERMANSON, G.T.: "Bioconjugate Techniques", 2008, ACADEMIC PRESS, pages: 215 - 342
HERMANSON, G.T.: "Bioconjugate Techniques", 2008, ACADEMIC PRESS, pages: 277 - 334
HINDS K D ET AL: "Effects of PEG conjugation of insulin properties", ADVANCED DRUG DELIVERY REVIEWS, ELSEVIER BV, AMSTERDAM, NL LNKD- DOI:10.1016/S0169-409X(02)00025-X, vol. 54, 1 January 2002 (2002-01-01), pages 505 - 530, XP003004966, ISSN: 0169-409X *
HINDS, K.D., KIM, S.W., ADVANCED DRUG DELIVERY REVIEWS, vol. 54, 2002, pages 505 - 530
HOPPE SEYLERS Z. PHYSIOL. CHEM., vol. 352, 1971, pages 1595 - 1598
HOPPE SEYLERS Z. PHYSIOL. CHEM., vol. 356, 1975, pages 1635 - 1649
HOPPE SEYLERS Z. PHYSIOL. CHEM., vol. 357, 1976, pages 1267 - 1270
HOPPE SEYLERS Z., PHYSIOL. CHEM., vol. 352, 1971, pages 1487 - 1490
HORNUNG, V. ET AL., NATURE MEDICINE, vol. 11, no. 3, 2005, pages 263 - 270
HUANG, J. ET AL., CHINESE CHEMICAL LETTERS, vol. 18, no. 3, 2007, pages 247 - 250
HUCKETT, B. ET AL., BIOCHEMICAL PHARMACOLOGY, vol. 40, no. 2, 1990, pages 253 - 63
IRL B HIRSCH: "Insulin Analogues", THE NEW ENGLAND JOURNAL OF MEDICINE, vol. 352, no. 2, 13 January 2005 (2005-01-13), pages 174 - 183, XP055003660, ISSN: 0028-4793 *
J. PHARMACEUTICAL SCIENCES, vol. 86, no. 11, 1997, pages 1264 - 1268
JACKSON, A.L. ET AL., RNA, vol. 12, 2006, pages 1 - 9
JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 86, no. 11, 1997, pages 1264 - 1268
JUDGE, A.D., MOLECULAR THERAPY, vol. 13, no. 3, 2006, pages 494 - 505
JULIANO, R., NUCLEIC ACIDS RESEARCH, vol. 36, no. 12, 2008, pages 4158 - 4171
KASIBHATLA, B. ET AL., CURRENT OPINION IN INVESTIGATIONAL DRUGS, vol. 8, no. 10, 2007, pages 805 - 813
KAWAKAMI, S., HASHIDA, M., DRUG METAB. PHARMACOKINET., vol. 22, no. 3, 2007, pages 142 - 151
KIM, D. H. ET AL., NATURE BIOTECHNOL., vol. 23, 2005, pages 222 - 226
KIM, D.H., ROSSI, J.J., NATURE REVIEWS GENETICS, vol. 8, 2007, pages 173 - 184
KORE, A.R., FORD, L.P., CURRENT BIOACTIVE COMPOUNDS, vol. 4, 2008, pages 6 - 14
KUMAR, P. ET AL., NATURE, vol. 448, 2007, pages 39 - 43
KURTZHALS, P. ET AL., BIOCHEM. J., vol. 312, 1995, pages 725 - 731
LIU, J. ET AL., SCIENCE, vol. 305, 2004, pages 1437 - 1441
MANOHARAN, M., CURRENT OPINION IN CHEMICAL BIOLOGY, vol. 8, 2004, pages 570 - 579
MARQUES, J.T. ET AL., NATURE BIOTECHNOLOGY, vol. 24, no. 5, 2006, pages 559 - 565
MEADE, B.R, DOWDY, S.F., ADVANCED DRUG DELIVERY REVIEWS, vol. 59, 2007, pages 134 - 140
MEADE, B.R., DOWDY, S.F., ADVANCED DRUG DELIVERY REVIEWS, vol. 59, 2007, pages 134 - 140
MURATOVSKA, A. ET AL., FEBS LETTERS, vol. 558, 2004, pages 63 - 68
NISHINA, K. ET AL., MOLECULAR THERAPY, vol. 16, no. 4, 2008
OISHI, M., BIOMACROMOLECULES, vol. 4, 2003, pages 1426 - 1432
OISHI, M., J. AM. CHEM. SOC., vol. 127, 2005, pages 1624 - 1625
OLIVIERA, S. ET AL., JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, vol. 63675, 2006, pages 1 - 9
PEPTIDE SCIENCE, vol. 88, no. 5, 2007, pages 687 - 713
POZNANSKY, M. J. ET AL., SCIENCE, vol. 223, no. 4642, 1984, pages 1304 - 6
RANA,T.M., NAT. REV. MOL. CELL. BIOL., vol. 8, 2007, pages 23 - 36
SHEN, Y., DRUGS, vol. 11, no. 8, 2008, pages 572 - 578
SIOLAS, D. ET AL., NATURE BIOTECHNOL., vol. 23, 2005, pages 227 - 231
SNYDER, E.L., DOWDY, S.F., PHARM. RES., vol. 21, 2004, pages 389 - 393
SONG, J-J. ET AL., SCIENCE, vol. 305, 2004, pages 1434 - 1437
SOUTSCHEK, J. ET AL., NATURE, vol. 432, 2004, pages 173 - 178
TAM, S., SAIAH, E., DRUGS OF THE FUTURE, vol. 33, no. 2, 2008, pages 175 - 185
TAYLOR, S.K. ET AL., ANGEW. CHEM., vol. 121, 2009, pages 4458 - 4461
TOMARI, Y., ZAMORE P.D., GENES & DEV., vol. 19, 2005, pages 517 - 529
UCHIO, T. ET AL., ADVANCED DRUG DELIVERY REVIEWS, vol. 35, 1999, pages 289 - 306
UI-TEI, K. ET AL., JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2006, pages 1 - 8
UI-TEI, K. ET AL., NUCLEIC ACIDS RESEARCH, vol. 36, no. 7, 2008, pages 2136 - 2151
VOLKOV, A.A., OLIGONUCLEOTIDES, vol. 19, no. 2, 2009, pages 191 - 202
WOLFRUM, C. ET AL., NATURE BIOTECHNOLOGY, vol. 25, no. 10, 2007, pages 1149 - 1157
XIA, C. Q. ET AL., JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 295, no. 2, 2000, pages 594 - 600
XIA, C-F. ET AL., MOL. PHARMACEUTICS, 2009
YANG, M., MATTES, J., PHARMACOLOGY & THERAPEUTICS, vol. 117, 2008, pages 94 - 104
ZAMORE ET AL., CELL, vol. 101, 2000, pages 25 - 33
ZHANG, Y.-Q. ET AL., JOURNAL OF CONTROLLED RELEASE, vol. 115, no. 3, 2006, pages 307 - 315
ZHONG, Z-Y., LEE, S-Y., EXPERT OPINION IN INVESTIGATIONAL DRUGS, vol. 12, no. 2, 2003, pages 223 - 233
ZORKO, M., LANGEL, U., ADV. DRUG DELIV. REV., vol. 57, 2005, pages 529 - 545

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10117909B2 (en) 2008-10-17 2018-11-06 Sanofi-Aventis Deutschland Gmbh Combination of an insulin and a GLP-1 agonist
US9526764B2 (en) 2008-10-17 2016-12-27 Sanofi-Aventis Deutschland Gmbh Combination of an insulin and a GLP-1-agonist
US10029011B2 (en) 2009-11-13 2018-07-24 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1 agonist, an insulin and methionine
US9707176B2 (en) 2009-11-13 2017-07-18 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1 agonist and methionine
US10028910B2 (en) 2009-11-13 2018-07-24 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1-agonist and methionine
US9345750B2 (en) 2010-05-19 2016-05-24 Sanofi Long-acting formulations of insulin
US9981013B2 (en) 2010-08-30 2018-05-29 Sanofi-Aventis Deutschland Gmbh Use of AVE0010 for the treatment of diabetes mellitus type 2
US9821032B2 (en) 2011-05-13 2017-11-21 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
US9408893B2 (en) 2011-08-29 2016-08-09 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for use in glycemic control in diabetes type 2 patients
US9987332B2 (en) 2011-09-01 2018-06-05 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition for use in the treatment of a neurodegenerative disease
US9364519B2 (en) 2011-09-01 2016-06-14 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition for use in the treatment of a neurodegenerative disease
US9908908B2 (en) 2012-08-30 2018-03-06 Jiangsu Hansoh Pharmaceutical Co., Ltd. Tenofovir prodrug and pharmaceutical uses thereof
US10092513B2 (en) 2013-04-03 2018-10-09 Sanofi Treatment of diabetes mellitus by long-acting formulations of insulins
US11191722B2 (en) 2013-04-03 2021-12-07 Sanofi Treatment of diabetes mellitus by long-acting formulations of insulins
US9950039B2 (en) 2014-12-12 2018-04-24 Sanofi-Aventis Deutschland Gmbh Insulin glargine/lixisenatide fixed ratio formulation
US10434147B2 (en) 2015-03-13 2019-10-08 Sanofi-Aventis Deutschland Gmbh Treatment type 2 diabetes mellitus patients
US10159713B2 (en) 2015-03-18 2018-12-25 Sanofi-Aventis Deutschland Gmbh Treatment of type 2 diabetes mellitus patients
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
US11981703B2 (en) 2017-08-17 2024-05-14 Sirius Therapeutics, Inc. Polynucleotide constructs

Also Published As

Publication number Publication date
UY33326A (es) 2011-12-01
TW201141513A (en) 2011-12-01
AR080884A1 (es) 2012-05-16

Similar Documents

Publication Publication Date Title
WO2011128374A1 (fr) Conjugués insuline-arnsi
US20220389424A1 (en) Modified double-stranded rna agents
US9895448B2 (en) Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
US7919473B2 (en) IRNA agents targeting VEGF
Watts et al. Chemically modified siRNA: tools and applications
JP2024045156A (ja) 十分に安定化された非対称ｓｉｒｎａ
Gaglione et al. Recent progress in chemically modified siRNAs
JP5352462B2 (ja) 二本鎖オリゴヌクレオチド複合体、ｒｎａ干渉による遺伝子サイレンシング方法、および医薬品組成物
KR102534909B1 (ko) 변형된 ＲＮＡｉ 제제
CN106701758B (zh) Hsp47表达的调节
TWI527901B (zh) A single stranded nucleic acid molecule used to control gene expression
Ezzat et al. Solid formulation of cell-penetrating peptide nanocomplexes with siRNA and their stability in simulated gastric conditions
US20110269814A1 (en) 2'-f modified rna interference agents
WO2016205410A2 (fr) Oligonucléotides multi-conjugués définis
Roberts et al. Synthetic SiRNA delivery: progress and prospects
KR20140012943A (ko) Timp1 및 timp2 발현의 조절
JP6808710B2 (ja) 核酸分子を安定に含有する組成物
AU2006287481A1 (en) Pharmaceutical compositions for delivery of ribonucleic acid to a cell
US9970002B2 (en) Compositions and methods for functional nucleic acid delivery
WO2011135140A1 (fr) Procédé pour l'administration d'oligonucléotides
KR20220115579A (ko) 표적화된 핵산 전달을 위한 펩티드 도킹 비히클
US20070276134A1 (en) Compositions and methods for complexes of nucleic acids and organic cations
WO2010059829A2 (fr) Compositions et procédés pour la libération déclenchée de produits thérapeutiques à base d'arn
AU2019204150A1 (en) Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
Langel Methods for CPP Functionalization with Oligonucleotides

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11715681

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11715681

Country of ref document: EP

Kind code of ref document: A1