IP Library › Granted Patent US 12,410,430
Granted Patent B2
US 12,410,430 · App. 18/315,890 · Granted Sep 9, 2025

Modulating apolipoprotein (A) expression

Inventors: Nicholas J. Viney (Carlsbad, CA); Richard S. Geary (Carlsbad, CA); Yanfeng Wang (Carlsbad, CA); Zhengrong Yu (Carlsbad, CA)
C12N15/113A61J1/05A61K9/0019A61K9/08A61K31/7125C07K14/775C12N2310/11C12N2310/315C12N2310/341C12N2310/351C12N2310/3515C12N2320/32C12N2320/35
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,410,430
App. No.
18/315,890
Granted
Sep 9, 2025
Kind
B2
Abstract

Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a) [apo(a)]. In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Claims (6)

1. A method of treating a disease or condition in a human, the method comprising administering to the human 75 mg to 85 mg of a compound or pharmaceutically acceptable salt thereof wherein the compound comprises a modified oligonucleotide having the nucleobase sequence of SEQ ID NO.: 1 and the compound has the structure as shown in FIG. 7

and wherein the disease or condition is calcific aortic valve stenosis.

2. The method of claim 1 , wherein about 80 mg of the compound is administered.

3. The method of claim 1 , wherein 80 mg of the compound is administered.

4. The method of claim 1 , wherein the compound is administered as a sodium salt.

5. The method of claim 4 , wherein the sodium salt has the structure as shown in FIG. 8 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2023
From: VINEY, NICHOLAS J.; GEARY, RICHARD S.; WANG, YANFENG; YU, ZHENGRONG
To: IONIS PHARMACEUTICALS, INC.
Reel/Frame 063710/0188 →
Continuity (6)
Continuation 17934605 · Sep 23, 2022
Continuation 17674450 · Feb 17, 2022
Continuation 16729980 · Dec 30, 2019
Continuation 15772649
Provisional Application 62252392 · Nov 6, 2015
Related Publication 20240218361A1 · Jul 4, 2024
References Cited (400)
US 3687808A · Merigan, Jr. et al. · 1972 [cited by applicant]
US 4469863A · Ts et al. · 1984 [cited by applicant]
US 4751219A · Kempen · 1988 [cited by applicant]
US 4845205A · Huynh et al. · 1989 [cited by applicant]
US 4981957A · Lebleu et al. · 1991 [cited by applicant]
US 5023243A · Tullis · 1991 [cited by applicant]
US 5034506A · Summerton et al. · 1991 [cited by applicant]
US 5118800A · Smith et al. · 1992 [cited by applicant]
US 5130302A · Spielvogel et al. · 1992 [cited by applicant]
US 5134066A · Rogers et al. · 1992 [cited by applicant]
US 5166315A · Summerton et al. · 1992 [cited by applicant]
US 5175273A · Bischofberger et al. · 1992 [cited by applicant]
US 5177198A · Spielvogel et al. · 1993 [cited by applicant]
US 5185444A · Summerton et al. · 1993 [cited by applicant]
US 5223618A · Cook et al. · 1993 [cited by applicant]
US 5256775A · Froehler · 1993 [cited by applicant]
US 5264562A · Matteucci · 1993 [cited by applicant]
US 5264564A · Matteucci · 1993 [cited by applicant]
US 5319080A · Leumann · 1994 [cited by applicant]
US 5359044A · Cook et al. · 1994 [cited by applicant]
US 5366878A · Pederson et al. · 1994 [cited by applicant]
US 5367066A · Urdea et al. · 1994 [cited by applicant]
US 5378825A · Cook et al. · 1995 [cited by applicant]
US 5386023A · Sanghvi et al. · 1995 [cited by applicant]
US 5393878A · Leumann · 1995 [cited by applicant]
US 5432272A · Benner · 1995 [cited by applicant]
US 5434257A · Matteucci et al. · 1995 [cited by applicant]
US 5446137A · Maag et al. · 1995 [cited by applicant]
US 5457187A · Gmeiner et al. · 1995 [cited by applicant]
US 5459255A · Cook et al. · 1995 [cited by applicant]
US 5466786A · Buhr et al. · 1995 [cited by applicant]
US 5476925A · Letsinger et al. · 1995 [cited by applicant]
US 5484908A · Froehler et al. · 1996 [cited by applicant]
US 5489677A · Sanghvi et al. · 1996 [cited by applicant]
US 5502177A · Matteucci et al. · 1996 [cited by applicant]
US 5508270A · Baxter et al. · 1996 [cited by applicant]
US 5514785A · Van et al. · 1996 [cited by applicant]
US 5519134A · Acevedo et al. · 1996 [cited by applicant]
US 5525711A · Hawkins et al. · 1996 [cited by applicant]
US 5552540A · Haralambidis · 1996 [cited by applicant]
US 5567811A · Misiura et al. · 1996 [cited by applicant]
US 5576427A · Cook et al. · 1996 [cited by applicant]
US 5587469A · Cook et al. · 1996 [cited by applicant]
US 5591722A · Montgomery et al. · 1997 [cited by applicant]
US 5594121A · Froehler et al. · 1997 [cited by applicant]
US 5596091A · Switzer · 1997 [cited by applicant]
US 5597909A · Urdea et al. · 1997 [cited by applicant]
US 5602240A · Mesmaeker et al. · 1997 [cited by applicant]
US 5610289A · Cook et al. · 1997 [cited by applicant]
US 5610300A · Altmann et al. · 1997 [cited by applicant]
US 5614617A · Cook et al. · 1997 [cited by applicant]
US 5625050A · Beaton et al. · 1997 [cited by applicant]
US 5627053A · Usman et al. · 1997 [cited by applicant]
US 5639873A · Barascut et al. · 1997 [cited by applicant]
US 5645985A · Froehler et al. · 1997 [cited by applicant]
US 5646265A · Mcgee · 1997 [cited by applicant]
US 5670633A · Cook et al. · 1997 [cited by applicant]
US 5681941A · Cook et al. · 1997 [cited by applicant]
US 5698685A · Summerton et al. · 1997 [cited by applicant]
US 5700920A · Altmann et al. · 1997 [cited by applicant]
US 5750692A · Cook et al. · 1998 [cited by applicant]
US 5763588A · Matteucci et al. · 1998 [cited by applicant]
US 5792847A · Buhr et al. · 1998 [cited by applicant]
US 5801154A · Baracchini et al. · 1998 [cited by applicant]
US 5830653A · Froehler et al. · 1998 [cited by applicant]
US 5877022A · Stinchcomb et al. · 1999 [cited by applicant]
US 5994517A · Ts et al. · 1999 [cited by applicant]
US 5998203A · Matulic-Adamic et al. · 1999 [cited by applicant]
US 6005096A · Matteucci et al. · 1999 [cited by applicant]
US 6268490B1 · Imanishi et al. · 2001 [cited by applicant]
US 6300319B1 · Manoharan · 2001 [cited by applicant]
US 6383812B1 · Chen et al. · 2002 [cited by applicant]
US 6525031B2 · Manoharan · 2003 [cited by applicant]
US 6525191B1 · Ramasamy · 2003 [cited by applicant]
US 6582908B2 · Fodor et al. · 2003 [cited by applicant]
US 6600032B1 · Manoharan et al. · 2003 [cited by applicant]
US 6620916B1 · Takahara et al. · 2003 [cited by applicant]
US 6660720B2 · Manoharan · 2003 [cited by applicant]
US 6670461B1 · Wengel et al. · 2003 [cited by applicant]
US 6770748B2 · Imanishi et al. · 2004 [cited by applicant]
US 6794499B2 · Wengel et al. · 2004 [cited by applicant]
US 6906182B2 · Ts et al. · 2005 [cited by applicant]
US 6908903B1 · Theodore et al. · 2005 [cited by applicant]
US 7034133B2 · Wengel et al. · 2006 [cited by applicant]
US 7053207B2 · Wengel · 2006 [cited by applicant]
US 7259150B2 · Crooke et al. · 2007 [cited by applicant]
US 7262177B2 · Ts et al. · 2007 [cited by applicant]
US 7267819B2 · Ferrara et al. · 2007 [cited by applicant]
US 7399845B2 · Seth et al. · 2008 [cited by applicant]
US 7407943B2 · Crooke et al. · 2008 [cited by applicant]
US 7427672B2 · Imanishi et al. · 2008 [cited by applicant]
US 7439043B2 · Defrees et al. · 2008 [cited by applicant]
US 7491805B2 · Vargeese et al. · 2009 [cited by applicant]
US 7569686B1 · Bhat et al. · 2009 [cited by applicant]
US 7582744B2 · Manoharan et al. · 2009 [cited by applicant]
US 7598227B2 · Crooke et al. · 2009 [cited by applicant]
US 7723509B2 · Manoharan et al. · 2010 [cited by applicant]
US 7741457B2 · Seth et al. · 2010 [cited by applicant]
US 7851615B2 · Manoharan et al. · 2010 [cited by applicant]
US 7935796B2 · Lee et al. · 2011 [cited by applicant]
US 8106022B2 · Manoharan et al. · 2012 [cited by applicant]
US 8137695B2 · Rozema et al. · 2012 [cited by applicant]
US 8138328B2 · Crooke et al. · 2012 [cited by applicant]
US 8158601B2 · Chen et al. · 2012 [cited by applicant]
US 8313772B2 · Rozema et al. · 2012 [cited by applicant]
US 8344125B2 · Manoharan et al. · 2013 [cited by applicant]
US 8349308B2 · Yurkovetskiy et al. · 2013 [cited by applicant]
US 8404862B2 · Manoharan et al. · 2013 [cited by applicant]
US 8435491B2 · Wang et al. · 2013 [cited by applicant]
US 8450467B2 · Manoharan et al. · 2013 [cited by applicant]
US 8501805B2 · Seth et al. · 2013 [cited by applicant]
US 8501930B2 · Rozema et al. · 2013 [cited by applicant]
US 8530640B2 · Seth et al. · 2013 [cited by applicant]
US 8541376B2 · Ferrara et al. · 2013 [cited by applicant]
US 8541548B2 · Rozema · 2013 [cited by applicant]
US 8546556B2 · Seth et al. · 2013 [cited by applicant]
US 8552163B2 · Lee et al. · 2013 [cited by applicant]
US 8653047B2 · Crooke et al. · 2014 [cited by applicant]
US 8673632B2 · Crooke et al. · 2014 [cited by applicant]
US 8742075B2 · Lee et al. · 2014 [cited by applicant]
US 9127276B2 · Prakash et al. · 2015 [cited by applicant]
US 9145558B2 · Prakash et al. · 2015 [cited by applicant]
US 9163239B2 · Prakash et al. · 2015 [cited by applicant]
US 9181550B2 · Prakash et al. · 2015 [cited by applicant]
US 9585859B2 · Osterloh et al. · 2017 [cited by applicant]
US 9884045B2 · Takahashi · 2018 [cited by applicant]
US 9957505B2 · Hauser · 2018 [cited by applicant]
US 10280423B2 · Prakash et al. · 2019 [cited by applicant]
US 10294477B2 · Swayze · 2019 [cited by applicant]
US 20010053519A1 · Fodor et al. · 2001 [cited by applicant]
US 20030017488A1 · Koishi et al. · 2003 [cited by applicant]
US 20030077829A1 · Maclachlan · 2003 [cited by applicant]
US 20030119724A1 · Ts et al. · 2003 [cited by applicant]
US 20030170249A1 · Hakomori et al. · 2003 [cited by applicant]
US 20030228597A1 · Cowsert et al. · 2003 [cited by applicant]
US 20040171570A1 · Allerson et al. · 2004 [cited by applicant]
US 20040242516A1 · Crooke et al. · 2004 [cited by applicant]
US 20050009088A1 · Crooke et al. · 2005 [cited by applicant]
US 20050130923A1 · Bhat et al. · 2005 [cited by applicant]
US 20050164235A1 · Manoharan et al. · 2005 [cited by applicant]
US 20050255487A1 · Khvorova et al. · 2005 [cited by applicant]
US 20060148740A1 · Platenburg · 2006 [cited by applicant]
US 20060183886A1 · Tso et al. · 2006 [cited by applicant]
US 20070031844A1 · Khvorova et al. · 2007 [cited by applicant]
US 20070054856A1 · Gerber et al. · 2007 [cited by applicant]
US 20070287831A1 · Seth et al. · 2007 [cited by applicant]
US 20080039618A1 · Allerson et al. · 2008 [cited by applicant]
US 20080108801A1 · Manoharan et al. · 2008 [cited by applicant]
US 20080113351A1 · Naito et al. · 2008 [cited by applicant]
US 20080177045A1 · Lee et al. · 2008 [cited by applicant]
US 20080206869A1 · Smith et al. · 2008 [cited by applicant]
US 20080255030A1 · Yu et al. · 2008 [cited by applicant]
US 20080281041A1 · Rozema et al. · 2008 [cited by applicant]
US 20080281044A1 · Monahan et al. · 2008 [cited by applicant]
US 20090012281A1 · Swayze et al. · 2009 [cited by applicant]
US 20090203132A1 · Swayze et al. · 2009 [cited by applicant]
US 20090203135A1 · Forst et al. · 2009 [cited by applicant]
US 20090286973A1 · Manoharan et al. · 2009 [cited by applicant]
US 20090306180A1 · Bhanot et al. · 2009 [cited by applicant]
US 20090318536A1 · Freier et al. · 2009 [cited by applicant]
US 20090326040A1 · Geary et al. · 2009 [cited by applicant]
US 20100240730A1 · Beigelman et al. · 2010 [cited by applicant]
US 20100331390A1 · Crooke et al. · 2010 [cited by applicant]
US 20110039910A1 · Crooke et al. · 2011 [cited by applicant]
US 20110077386A1 · Lee et al. · 2011 [cited by applicant]
US 20110097264A1 · Wang et al. · 2011 [cited by applicant]
US 20110097265A1 · Wang et al. · 2011 [cited by applicant]
US 20110123520A1 · Manoharan et al. · 2011 [cited by applicant]
US 20110201798A1 · Manoharan · 2011 [cited by applicant]
US 20110207799A1 · Rozema et al. · 2011 [cited by applicant]
US 20110243948A1 · Lee et al. · 2011 [cited by applicant]
US 20110269814A1 · Manoharan et al. · 2011 [cited by applicant]
US 20120035115A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120095075A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120101148A1 · Aking et al. · 2012 [cited by applicant]
US 20120122958A1 · Dawson et al. · 2012 [cited by applicant]
US 20120128760A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120136042A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120157509A1 · Hadwiger et al. · 2012 [cited by applicant]
US 20120165393A1 · Rozema et al. · 2012 [cited by applicant]
US 20120183602A1 · Chen et al. · 2012 [cited by applicant]
US 20120230938A1 · Rozema et al. · 2012 [cited by applicant]
US 20130004427A1 · El-Sayed et al. · 2013 [cited by applicant]
US 20130017250A1 · Ginsberg et al. · 2013 [cited by applicant]
US 20130023579A1 · Crooke et al. · 2013 [cited by applicant]
US 20130109817A1 · Yurkovetskiy et al. · 2013 [cited by applicant]
US 20130121954A1 · Wakefield et al. · 2013 [cited by applicant]
US 20130178512A1 · Manoharan et al. · 2013 [cited by applicant]
US 20130236968A1 · Manoharan et al. · 2013 [cited by applicant]
US 20130281511A1 · Bettencourt et al. · 2013 [cited by applicant]
US 20130317085A1 · Crooke et al. · 2013 [cited by applicant]
US 20140206750A1 · Crooke et al. · 2014 [cited by applicant]
US 20140343123A1 · Prakash et al. · 2014 [cited by applicant]
US 20140350090A1 · Bhat et al. · 2014 [cited by applicant]
US 20150057329A1 · Bhanot et al. · 2015 [cited by applicant]
US 20150126719A1 · Prakash et al. · 2015 [cited by applicant]
US 20150126720A1 · Prakash et al. · 2015 [cited by applicant]
US 20150164850A1 · Osterloh et al. · 2015 [cited by applicant]
US 20150167005A1 · Freier et al. · 2015 [cited by applicant]
US 20150184156A1 · Crooke et al. · 2015 [cited by applicant]
US 20150291958A1 · Albaek et al. · 2015 [cited by applicant]
US 20180256629A1 · Crooke et al. · 2018 [cited by applicant]
US 20200362340A1 · Viney et al. · 2020 [cited by applicant]
CA 2450022A1 · 2002 [cited by applicant]
CA 2874480A1 · 2013 [cited by applicant]
NO 0105825A2 · 2001 [cited by applicant]
WO 9402499A1 · 1994 [cited by applicant]
WO 9417093A1 · 1994 [cited by applicant]
WO 9614329A1 · 1996 [cited by applicant]
WO 9720563A1 · 1997 [cited by applicant]
WO 9746098A1 · 1997 [cited by applicant]
WO 9813381A1 · 1998 [cited by applicant]
WO 9839352A1 · 1998 [cited by applicant]
WO 9914226A2 · 1999 [cited by applicant]
WO 0014048A1 · 2000 [cited by applicant]
WO 0063364A2 · 2000 [cited by applicant]
WO 0243771A2 · 2002 [cited by applicant]
WO 0149687A2 · 2002 [cited by applicant]
WO 03004602A2 · 2003 [cited by applicant]
WO 03014307A2 · 2003 [cited by applicant]
WO 03014397A1 · 2003 [cited by applicant]
WO 03044172A2 · 2003 [cited by applicant]
WO 2004024757A2 · 2004 [cited by applicant]
WO 2004035765A2 · 2004 [cited by applicant]
WO 2004044181A2 · 2004 [cited by applicant]
WO 2004063208A1 · 2004 [cited by applicant]
WO 2004093783A2 · 2004 [cited by applicant]
WO 2004101619A1 · 2004 [cited by applicant]
WO 2004106356A1 · 2004 [cited by applicant]
WO 2005000201A2 · 2005 [cited by applicant]
WO 2005021570A1 · 2005 [cited by applicant]
WO 2005097155A1 · 2005 [cited by applicant]
WO 2005121371A2 · 2005 [cited by applicant]
WO 2006031461A2 · 2006 [cited by applicant]
WO 2006047842A2 · 2006 [cited by applicant]
WO 2007035759A1 · 2007 [cited by applicant]
WO 2007090071A2 · 2007 [cited by applicant]
WO 2007134181A2 · 2007 [cited by applicant]
WO 2008073300A2 · 2008 [cited by applicant]
WO 2008098788A2 · 2008 [cited by applicant]
WO 2008101157A1 · 2008 [cited by applicant]
WO 2008150729A2 · 2008 [cited by applicant]
WO 2008154401A2 · 2008 [cited by applicant]
WO 2009003009A1 · 2008 [cited by applicant]
WO 2009006478A2 · 2009 [cited by applicant]
WO 2009073809A2 · 2009 [cited by applicant]
WO 2009082607A2 · 2009 [cited by applicant]
WO 2009126933A2 · 2009 [cited by applicant]
WO 2009134487A2 · 2009 [cited by applicant]
WO 2009143369A2 · 2009 [cited by applicant]
WO 2010036696A1 · 2010 [cited by applicant]
WO 2010036698A1 · 2010 [cited by applicant]
WO 2010048549A2 · 2010 [cited by applicant]
WO 2010048585A2 · 2010 [cited by applicant]
WO 2010054406A1 · 2010 [cited by applicant]
WO 2010077578A1 · 2010 [cited by applicant]
WO 2010083615A1 · 2010 [cited by applicant]
WO 2010088537A2 · 2010 [cited by applicant]
WO 2010101951A1 · 2010 [cited by applicant]
WO 2010103204A1 · 2010 [cited by applicant]
WO 2010129709A1 · 2010 [cited by applicant]
WO 2010141511A2 · 2010 [cited by applicant]
WO 2010144740A1 · 2010 [cited by applicant]
WO 2010148013A2 · 2010 [cited by applicant]
WO 2011005860A2 · 2011 [cited by applicant]
WO 2011005861A1 · 2011 [cited by applicant]
WO 2011038356A2 · 2011 [cited by applicant]
WO 2011085271A2 · 2011 [cited by applicant]
WO 2011100131A2 · 2011 [cited by applicant]
WO 2011115818A1 · 2011 [cited by applicant]
WO 2011120053A1 · 2011 [cited by applicant]
WO 2011133871A2 · 2011 [cited by applicant]
WO 2011139702A2 · 2011 [cited by applicant]
WO 2011163121A1 · 2011 [cited by applicant]
WO 2012037254A1 · 2012 [cited by applicant]
WO 2012068187A1 · 2012 [cited by applicant]
WO 2012083046A2 · 2012 [cited by applicant]
WO 2012083185A2 · 2012 [cited by applicant]
WO 2012089352A1 · 2012 [cited by applicant]
WO 2012089602A1 · 2012 [cited by applicant]
WO 2012135736A2 · 2012 [cited by applicant]
WO 2012145674A1 · 2012 [cited by applicant]
WO 2012145697A1 · 2012 [cited by applicant]
WO 2012149495A1 · 2012 [cited by applicant]
WO 2012177784A2 · 2012 [cited by applicant]
WO 2012177947A2 · 2012 [cited by applicant]
WO 2013033230A1 · 2013 [cited by applicant]
WO 2013075035A1 · 2013 [cited by applicant]
WO 2013119979A1 · 2013 [cited by applicant]
WO 2013142571A2 · 2013 [cited by applicant]
WO 2013165816A2 · 2013 [cited by applicant]
WO 2013166121A1 · 2013 [cited by applicant]
WO 2013173789A2 · 2013 [cited by applicant]
WO 2013177468A2 · 2013 [cited by applicant]
WO 2014076195A1 · 2014 [cited by applicant]
WO 2014076196A1 · 2014 [cited by applicant]
WO 2014118267A1 · 2014 [cited by applicant]
WO 2014118272A1 · 2014 [cited by applicant]
WO 2014179620A1 · 2014 [cited by applicant]
WO 2014179625A1 · 2014 [cited by applicant]
WO 2014179626A2 · 2014 [cited by applicant]
WO 2014179627A2 · 2014 [cited by applicant]
WO 2014179629A2 · 2014 [cited by applicant]
WO 2014184973A1 · 2014 [cited by applicant]
WO 2014205451A2 · 2014 [cited by applicant]
WO 2014207232A1 · 2014 [cited by applicant]
WO 2015168532A2 · 2015 [cited by applicant]
WO 2015168589A2 · 2015 [cited by applicant]
WO 2015168635A2 · 2015 [cited by applicant]
WO 2017079739A1 · 2017 [cited by applicant]
WO 2017079745A1 · 2017 [cited by applicant]
Pia R. Kamstrup et al., Journal of the American College of Cardiology vol. 63, (No. 5):440-477, 2014. [cited by examiner]
Akinc, et al., Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms, Molecular Therapy, Jul. 2010, 1357-1364, 18(7). [cited by applicant]
Albaek, et al., Analogus of a Locked Nucleic Acid with Three-Carbon 2′,4′-Linkages: Synthesis by Ring-Closing Metathesis and Influence on Nucleic Acid Duplex Stability and Structure, J. Org. Chem., 2006, 7731-7740, 71(2… [cited by applicant]
Allshire, RNAi and Heterochromatin—a Hushed-Up Affair, Science, Sep. 13, 2002, 1818-1819, 297. [cited by applicant]
Altmann, et al., Second Generation Antisense Oligonucleotides-Inhibition of PKC-a and c-raf Kinase Expression by Chimeric Oligonucleotides Incorporating 6″-Substituted Carbocyclic Nucleosides and 2″-O-Ethylene Glycol Su… [cited by applicant]
Altmann, et al., Second Generation of Antisense Oligonucleotides: From Nuclease Resistance to Biological Efficacy in Animals, Chimia, 1996, 168-176, 50(4). [cited by applicant]
Altmann, et al., Second-generation antisense oligonucleotides: structure-activity relationships and the design of improved signal-transduction inhibitors, Biochemical Society Transaction, 1996, 630-637, 24. [cited by applicant]
Ando, et al., A decreased expression of angiopoietin-like 3 is protective against atherosclerosis in apoE-deficient mice, Journal of Lipid Research, 2003, 1216-1223, 44. [cited by applicant]
Andre, et al., Determination of modulation of ligand properties of synthetic complex-type biantennary N-glycans by introduction of bisecting GlcNAc in silico, in vitro and in vivo, Eur. J. Biochem., 2004, 118-134, 271. [cited by applicant]
Angelakopoulou, et al., Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration, European Heart Journal, 2012, 39… [cited by applicant]
Asseline, Modification of the 5′ Terminus of Oligonucleotides for Attachment of Reporter and Conjugate Groups, Current Protocols in Nucleic Acid Chemistry, 2000, 4.2.1-4.2.33. [cited by applicant]
Atsma, et al., Partial characterization of low density lipoprotein preparations isolated from fresh and frozen plasma after radiolabeling by seven different methods, Journal of Lipid Research, 1991, 173-181, 32. [cited by applicant]
Baker, et al., 2′-O-(2-Methoxy)ethyl-modified Anti-intercellular Adhesion Molecule 1 (ICAM-1) Oligonucleotides Selectively Increase ICAM-1 mRNA Level and Inhibit Formation of the ICAM-1 Translation Initiation Complex in… [cited by applicant]
Beaucage et, al., The functionalization of oligonucleotides via phosphoramidite derivatives, Tetrahedron, Mar. 5, 1993, 1925-1963, 49(10). [cited by applicant]
Bennett, Pharmacological properties of 2′-O-methoxyethyl modified oligonucleotides, Antisense Drug Technology, 2008, 273-303, chapter 10. [cited by applicant]
Bergmark, et al., A novel function of lipoprotein (a) as a preferential carrier of oxidized phospholipids in human plasma, Journal of Lipid Research, 2008, 2230-2239, 49. [cited by applicant]
Biessen, et al., Novel hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine with improved pharmacokinetics and antiviral activity, FASEB Journal, 2000, 1784-1792, 14. [cited by applicant]
Biessen, et al., Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor, J. Med. Chem., Apr. 1995, 1538-1546, 38. [cited by applicant]
Biessen, et al., The Cholesterol Derivative of a Triantennary Galactoside with High Affinity for the Hepatic Asialoglycoprotein Receptor: a Potent Cholesterol Lowering Agent, J. Med. Chem., May 1995, 1846-1852, 38. [cited by applicant]
Bligh, et al., A rapid method of total lipid extraction and purification, Canadian Journal of Biochemistry and Physiology, Aug. 1959, 911-917, 37(8). [cited by applicant]
Braasch, et al., Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA, Chemistry & Biology, 2001, 1-7, 8(1). [cited by applicant]
Braasch, et al., Novel antisense and peptide nucleic acid strategies for controlling gene expression, Biochemistry, Apr. 9, 2002, 4503-4510, 41(14). [cited by applicant]
Branch, A good antisense molecule is hard to find, TIBS, Feb. 1998, 45-50, 23. [cited by applicant]
Branda, et al., Amplification of antibody production by phosphorothioate oligodeoxynucleotides, J Lab Clin Med, Sep. 1996, 329-338, 128(3). [cited by applicant]
Browning, et al., Molecular mediators of hepatic steatosis and liver injury, Journal of Clinical Investigation, Jul. 2004, 147-152, 114(2). [cited by applicant]
Camenisch, et al., ANGPTL3 Stimulates Endothelial Cell Adhesion and Migration via Integrin avb3 and Induces Blood Vessel Formation in Vivo, Journal of Biological Chemistry, May 10, 2002, 17281-17290, 277(19). [cited by applicant]
Chin, On the Preparation and Utilization of Isolated and Purified Oligonucleotides, Mar. 9, 2002. [cited by applicant]
Clarke, et al., Genetic variants associated with Lp(a) lipoprotein level and coronary disease, N Engl J Med, Dec. 24, 2009, 2518-2528, 361(26). [cited by applicant]
Coltart, et al., Principles of Mucin Architecture: Structural Studies on Synthetic Glycopeptides Bearing Clustered Mono-, Di-, Tri-, and Hexasaccharide Glycodomains, J. Am. Chem. Soc., 2002, 9833-9844, 124. [cited by applicant]
Conklin, et al., Identification of a Mammalian Angiopoietin-Related Protein Expressed Specifically in Liver, Genomics, 1999, 477-482, 62. [cited by applicant]
Connolly, et al., Binding and Endocytosis of Cluster Glycosides by Rabbit Hepatocytes, Journal of Biological Chemistry, Jan. 25, 1982, 939-945, 257(2). [cited by applicant]
Crooke, Basic Principles of Antisense Therapeutic, Antisense Research and Application, 1998, 1-50. [cited by applicant]
Crooke, et al., Pharmacokinetic Properties of Several Novel Oligonucleotide Analogs in Mice, The Journal of Pharmacology and Experimental Therapeutics, 1996, 923-937, 277(2). [cited by applicant]
Czech, et al., RNAi-based therapeutic strategies for metabolic disease, Nature Reviews Endocrinology, Aug. 2011, 473-484, 7. [cited by applicant]
Davidson, et al., Apolipoprotein B: mRNA Editing, Lipoprotein Assembly, and Presecretory Degradation, Annu. Rev. Nutr., 2000, 169-193, 20. [cited by applicant]
Dellinger, et al., Solid-Phase Chemical Synthesis of Phosphonoacetate and Thiophosphonoacetate Oligodeoxynucleotides, J. Am. Chem. Soc., 2003, 940-950, 125. [cited by applicant]
Duff, et al., Intrabody Tissue-Specific Delivery of Antisense Conjugates in Animals: Ligand-Linker-Antisense Oligomer Conjugates, Methods in Enzymology, 2000, 297-321, 313. [cited by applicant]
Dupouy, et al., Watson-Crick Base-Pairing Properties of Nucleic Acid Analogues with Stereocontrolled a and b Torsion Angles (a,b-D-CNAs), Angew. Chem. Int. Ed., 2006, 3623-3627, 45. [cited by applicant]
Elayadi, et al., Application of PNA and LNA oligomers to chemotherapy, Current Opinion In Investigational Drugs, 2001, 558-561, 2(4). [cited by applicant]
EMBL Accession No. BG400407.1, [cited by applicant]
Englisch, et al., Chemically Modified Oligonucleotides as Probes and Inhibitors, Angew Chem Int Ed Eng, Jun. 1991, 613-629, 30(6). [cited by applicant]
Erqou, et al., Lipoprotein (a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality, JAMA, 2009, 412-423, 302(4). [cited by applicant]
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Jama, May … [cited by applicant]
Fredrickson, et al., A system for phenotyping hyperlipoproteinemia, Circulation, Mar. 1965, 321-327, 31. [cited by applicant]
Fredrickson, et al., Fat transport in lipoproteins-an integrated approach to mechanisms and disorders, N Engl J Med, Jan. 5, 1967, 34-42, 276(1). [cited by applicant]
Freier, et al., The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA: RNA duplexes, Nucleic Acids Research, 1997, 4429-4443, 25(22). [cited by applicant]
Frieden, et al., Expanding the design horizon of antisense oligonucleotides with alpha-L-LNA, Nucleic Acids Research, 2003, 6365-6372, 31(21). [cited by applicant]
Fujimoto, et al., Angptl3-null mice show low plasma lipid concentrations by enhanced lipoprotein lipase activity, Exp. Anim., 2006, 27-34, 55(1). [cited by applicant]
Gao, et al., Angiopoietin-like protein 3 regulates the motility and permeability of podocytes by altering nephrin expression in vitro, Biochemical and Biophysical Research Communications, Jul. 13, 2010, 31-36, 399. [cited by applicant]
Gautschi, et al., Activity of a Novel bcl-2/bcl-xL-Bispecific Antisense Oligonucleotide Against Tumors of Diverse Histologic Origins, Journal of the National Cancer Institute, Mar. 21, 2001, 463-471, 93(6). [cited by applicant]
Geary, et al., A Nonradioisotope Biomedical Assay for Intact Oligonucleotide and Its Chain-Shortened Metabolites Used for Determination of Exposure and Elimination Half-Life of Antisense Drugs in Tissue, Analytical Bioc… [cited by applicant]
Geary, et al., Pharmacokinetic Properties of 29-O-(2-Methoxyethyl)-Modified Oligonucleotide Analogs in Rats, Journal of Pharmacology and Experimental Therapeutics, 2001, 890-897, 296. [cited by applicant]
GenBank accession No. NM014495.1, [cited by applicant]
Goodman, Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Arch Intern Med, Jan. 1988, 36-69, 148. [cited by applicant]
Graham, et al., Antisense inhibition of apolipoprotein(a) in cynomolgus monkeys significantly reduces plasma apolipoprotein(a) levels without affecting plasminogen or other major lipid classes, Circulation, 2012, Abstra… [cited by applicant]
Graham, et al., Antisense Oligonucleotide Inhibition of Apolipoprotein C-III Reduces Plasma Triglycerides in Rodents, Nonhuman Primates, and Humans, Circulation Research, May 24, 2013, 1479-1490, 112. [cited by applicant]
Gu, et al., Base Pairing Properties of D- and L-Cyclohexene Nucleic Acids (CeNA), Oligonucleotides, 2003, 479-489, 13. [cited by applicant]
Gu, et al., Enzymatic resolution and base pairing properties of D- and L-cyclohexenyl nucleic acids (CeNA), Nucleosides Nucleotides Nucleic Acids, 2005, 993-998, 24(5-7). [cited by applicant]
Gu, et al., Synthesis of enantiomeric-pure cyclohexenyl nucleoside building blocks for oligonucleotide synthesis, Tetrahedron, 2004, 2111-2123, 60. [cited by applicant]
Guzaev, et al., A Conformationally Preorganized Universal Solid Support for Efficient Oligonucleotide Synthesis, J. Am. Chem. Soc., 2003, 2380-2381, 125. [cited by applicant]
Hall, et al., Establishment and Maintenance of a Heterochromatin Domain, Science, Sep. 27, 2002, 2232-2237, 297. [cited by applicant]
Hanessian, et al., Synthesis of chemically and functionally diverse scaffolds from pentaerythritol, Can. J. Chem., 1996, 1731-1737, 74. [cited by applicant]
Hatsuda, et al., Association between Plasma Angiopoietin-Like Protein 3 and Arterial Wall Thickness in Healthy Subjects, J Vasc Res, 2007, 61-66, 44. [cited by applicant]
Henry, et al., Toxicologic properties od 2′O-Methoxyethyl chimeric antisense inhibitors in animals and man, Antisense Drug Technology, 2008, 327-363, chapter 12. [cited by applicant]
Hoffmann, et al., ‘Brain-type’ N-glycosylation of asialo-transferrin from human cerebrospinal fluid, FEBS Letters, 1995, 164-168, 359. [cited by applicant]
Hooper, et al., Recent developments in the genetics of LDL deficiency, Curr Opin Lipidol., Apr. 2013, 111-115, 24 (2). [cited by applicant]
Horn, et al., Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays, Nucleic Acids Research, 1997, 4842-4849, 25(23). [cited by applicant]
Horvath, et al., Stereoselective synthesis of (−)-ara-cyclohexenyl-adenine, Tetrahedron Letters, Mar. 12, 2007, 3621-3623, 48. [cited by applicant]
Ichimura, et al., Serum Angiopoietin-like Protein 3 Levels: Possible Correlation with Progressive Skin Sclerosis, Digital Ulcers and Pulmonary Vascular Involvement in Patients with Systemic Sclerosis, Acta Derm Venereol… [cited by applicant]
Inaba, et al., Angiopoietin-like Protein 3 Mediates Hypertriglyceridemia Induced by the Liver X Receptor, Journal of Biological Chemistry, Jun. 13, 2003, 21344-21351, 278(24). [cited by applicant]
Inukai, et al., ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states, Biochemical and Biophysical Research Communications, 2004, 1075-1079, 317. [cited by applicant]
Ishibashi, et al., Hypercholesterolemia in Low Density Lipoprotein Receptor Knockout Mice and its Reversal by Adenovirus-mediated Gene Delivery, Journal of Clinical Investigation, 1993, 883-893, 92(2). [cited by applicant]
Jayaprakash, et al., Non-Nucleoside Building Blocks for Copper-Assisted and Copper-Free Click Chemistry for the Efficient Synthesis of RNA Conjugates, Organic Letters, 2010, 5410-5413, 12(23). [cited by applicant]
Jenuwein, An RNA-Guided Pathway for the Epigenome, Science, Sep. 27, 2002, 2215-2218, 297. [cited by applicant]
Jiang, et al., The Design and Synthesis of Highly Branched and Spherically Symmetric Fluorinated Oils and Amphiles, Tetrahedron, May 7, 2007, 3982-3988, 63(19). [cited by applicant]
Jin, et al., Use of alpha-N, N-bis[carboxymethyl]lysine-modified peroxidase in immunoassays, Analytical Biochemistry, 1995, 54-60, 229. [cited by applicant]
Jones, et al., RNA Quantitation by Fluorescence-Based Solution Assay: RiboGreen Reagent Characterization, Analytical Biochemistry, 1998, 368-374, 265. [cited by applicant]
Kamstrup, et al., Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study, Circulation, Jan. 15, 2008, 176-184, 117. [cited by applicant]
Kanasty, et al., Delivery materials for siRNA therapeutics, Nature Materials, Nov. 2013, 967-977, 12. [cited by applicant]
Kaplan, et al., Regulation of the angiopoietin-like protein 3 gene by LXR, Journal of Lipid Research, 2003, 136-143, 44. [cited by applicant]
Kassim, et al., Gene therapy for dyslipidemia: a review of gene replacement and gene inhibition strategies, Clin Lipidol., Jun. 2010, 793-809, 5(6). [cited by applicant]
Kato, et al., N-acetylgalactosamine incorporation into a peptide containing consecutive threonine residues by UDP-N-acetyl-D-galactosaminide:polypeptide N-acetylgalactosaminyltransferases, Glycobiology, 2001, 821-829, 1… [cited by applicant]
Khorev, et al., Trivalent, GaI/GaINAc-containing ligands designed for the asialoglycoprotein receptor, Bioorganic & Medicinal Chemistry, 2008, 5216-5231, 16. [cited by applicant]
Kim, et al., Oligomeric Glycopeptidomimetics Bearing the Cancer Related TN-Antigen, Tetrahedron Letters, 1997, 3487-3490, 38(20). [cited by applicant]
Kim, et al., Synthesis of Novel Phosphoramidite Building Blocks from Pentaerythritol, Synlett, 2003, 1838-1840, 12. [cited by applicant]
Koishi, et al., Angptl3 regulates lipid metabolism in mice, Nature Genetics, Feb. 2002, 151-157, 30. [cited by applicant]
Koller, et al., Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes, Nucleic Acids Research, Feb. 23, 2011, 4795-4807, 39(11). [cited by applicant]
Komilova, et al., Development of a fluorescence polarization binding assay for asialoglycoprotein receptor, Analytical Biochemistry, 2012, 43-46, 425. [cited by applicant]
Korstanje, et al., Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans, Atherosclerosis, Sep. 27, 2004, 443-450, 177. [cited by applicant]