IP Library › Granted Patent US 12,618,069
Granted Patent B2
US 12,618,069 · App. 18/485,724 · Granted May 5, 2026

Compounds and methods for reducing ATXN3 expression

Inventor: Susan M. Freier (San Diego, CA)
Assignee: Ionis Pharmaceuticals, Inc.
C12N15/113C12N2310/315C12N2310/322C12N2310/3341C12N2310/346C12N2320/30
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 12,618,069
App. No.
18/485,724
Granted
May 5, 2026
Kind
B2
Abstract

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3 (SCA3).

Claims (42)

1 . An oligomeric compound comprising a modified oligonucleotide consisting of 12 to 50 linked nucleosides and having a nucleobase sequence comprising a portion of at least 8 contiguous nucleobases, wherein the portion is complementary to an equal length portion of nucleobases 34440-34486 of SEQ ID NO: 2.

2 . The oligomeric compound of claim 1 , consisting of a single-stranded modified oligonucleotide.

3 . The oligomeric compound of claim 1 , wherein at least one internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage.

4 . The oligomeric compound of claim 3 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.

5 . The oligomeric compound of claim 1 , wherein each internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage.

6 . The oligomeric compound of claim 5 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.

7 . The oligomeric compound of claim 1 , wherein at least one internucleoside linkage of the modified oligonucleotide is a phosphodiester internucleoside linkage.

8 . The oligomeric compound of claim 1 , wherein each internucleoside linkage of the modified oligonucleotide is either a phosphodiester internucleoside linkage or a phosphorothioate internucleoside linkage.

9 . The oligomeric compound of claim 1 , wherein at least one nucleobase of the modified oligonucleotide comprises a modified nucleobase.

10 . The oligomeric compound of claim 9 , wherein the modified nucleobase is a 5-methylcytosine.

11 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide comprises at least one modified nucleoside comprising a modified sugar moiety.

12 . The oligomeric compound of claim 11 , wherein the modified sugar moiety comprises a bicyclic sugar moiety.

13 . The oligomeric compound of claim 12 , wherein the bicyclic sugar moiety has a 2′-4′ bridge, wherein the 2′-4′ bridge is selected from —O—CH 2 —; and —O—CH(CH 3 )—.

14 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide comprises at least one modified nucleoside comprising a non-bicyclic sugar moiety.

15 . The oligomeric compound of claim 14 , wherein the non-bicyclic sugar moiety comprises a 2′-MOE or 2′-OMe.

16 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide comprises at least one modified nucleoside comprising a sugar surrogate.

17 . The oligomeric compound of claim 16 , wherein the sugar surrogate is selected from morpholino and PNA.

18 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide has a sugar motif comprising:

a 5′-region consisting of 1-6 linked 5′-nucleosides;

a central region consisting of 6-10 linked central region nucleosides; and

a 3′-region consisting of 1-6 linked 5′-nucleosides; wherein each of the 5′-region nucleosides and each of the 3′-region nucleosides comprises a modified sugar moiety and each of the central region nucleosides comprises a 2′-deoxyribosyl sugar moiety.

19 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide consists of 18-20 linked nucleosides.

20 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide consists of 20 linked nucleosides.

21 . The oligomeric compound of claim 1 comprising a conjugate group comprising a conjugate moiety and a conjugate linker.

22 . An oligomeric duplex comprising the oligomeric compound of claim 1 .

23 . A modified oligonucleotide consisting of 12 to 50 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 2233-2237, wherein the modified oligonucleotide comprises at least one modification selected from a modified sugar moiety and a modified internucleoside linkage.

24 . A pharmaceutical composition comprising the oligomeric compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

25 . The pharmaceutical composition of claim 24 , wherein the pharmaceutically acceptable diluent is artificial cerebrospinal fluid or phosphate-buffered saline (PBS).

26 . The pharmaceutical composition of claim 25 , wherein the pharmaceutical composition consists essentially of the oligomeric compound and artificial cerebrospinal fluid.

27 . The pharmaceutical composition of claim 25 , wherein the pharmaceutical composition consists essentially of the oligomeric compound and PBS.

28 . The modified oligonucleotide of claim 23 , wherein the modified sugar moiety comprises a bicyclic sugar moiety or a non-bicyclic sugar moiety.

29 . The modified oligonucleotide of claim 23 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.

30 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 10 contiguous nucleobases, wherein the portion is complementary to an equal length portion of nucleobases 34440-34486 of SEQ ID NO: 2.

31 . The modified oligonucleotide of claim 23 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 10 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 2233-2237.

32 . The modified oligonucleotide of claim 23 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 12 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 2233-2237.

33 . The modified oligonucleotide of claim 23 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 16 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 2233-2237.

34 . The modified oligonucleotide of claim 23 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 18 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 2233-2237.

35 . The modified oligonucleotide of claim 23 , wherein the modified oligonucleotide has a nucleobase sequence comprising at least 20 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 2233-2237.

36 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 12 contiguous nucleobases, wherein the portion is fully complementary to an equal length portion of nucleobases 34440-34486 of SEQ ID NO: 2.

37 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 16 contiguous nucleobases, wherein the portion is fully complementary to an equal length portion of nucleobases 34440-34486 of SEQ ID NO: 2.

38 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 18 contiguous nucleobases, wherein the portion is fully complementary to an equal length portion of nucleobases 34440-34486 of SEQ ID NO: 2.

39 . The oligomeric compound of claim 1 , wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 20 contiguous nucleobases, wherein the portion is fully complementary to an equal length portion of nucleobases 34440-34486 of SEQ ID NO: 2.

Continuity (4)
Continuation 17852939 · Jun 29, 2022
Continuation 17053997
Provisional Application 62669238 · May 9, 2018
Related Publication 20240301412A1 · Sep 12, 2024
References Cited (305)
US 3687808A · Merigan et al. · 1972 [cited by applicant]
US 4415732A · Caruthers et al. · 1983 [cited by applicant]
US 4469863A · Ts'o et al. · 1984 [cited by applicant]
US 4476301A · Imbach et al. · 1984 [cited by applicant]
US 4500707A · Caruthers et al. · 1985 [cited by applicant]
US 4725677A · Koster et al. · 1988 [cited by applicant]
US 4845205A · Huynh Dinh et al. · 1989 [cited by applicant]
US 4973679A · Caruthers et al. · 1990 [cited by applicant]
US 4981957A · Lebleu et al. · 1991 [cited by applicant]
US 5013830A · Ohutsuka 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 5132418A · Caruthers et al. · 1992 [cited by applicant]
US 5134066A · Rogers et al. · 1992 [cited by applicant]
US RE34036E · McGeehan · 1992 [cited by applicant]
US 5149797A · Pederson 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 5177196A · Meyer, Jr. et al. · 1993 [cited by applicant]
US 5177198A · Spielvogel et al. · 1993 [cited by applicant]
US 5185444A · Summerton et al. · 1993 [cited by applicant]
US 5188897A · Suhadolnik et al. · 1993 [cited by applicant]
US 5194599A · Froehler et al. · 1993 [cited by applicant]
US 5214134A · Weis et al. · 1993 [cited by applicant]
US 5216141A · Benner · 1993 [cited by applicant]
US 5220007A · Pederson et al. · 1993 [cited by applicant]
US 5223618A · Cook et al. · 1993 [cited by applicant]
US 5235033A · Summerton et al. · 1993 [cited by applicant]
US 5256775A · Froehler · 1993 [cited by applicant]
US 5264423A · Cohen et al. · 1993 [cited by applicant]
US 5264562A · Matteucci · 1993 [cited by applicant]
US 5264564A · Matteucci · 1993 [cited by applicant]
US 5276019A · Cohen et al. · 1994 [cited by applicant]
US 5286717A · Cohen et al. · 1994 [cited by applicant]
US 5319080A · Leumann · 1994 [cited by applicant]
US 5321131A · Agrawal et al. · 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 5399676A · Froehler · 1995 [cited by applicant]
US 5403711A · Walder et al. · 1995 [cited by applicant]
US 5405938A · Sumerton et al. · 1995 [cited by applicant]
US 5405939A · Suhadolnik et al. · 1995 [cited by applicant]
US 5432272A · Benner · 1995 [cited by applicant]
US 5434257A · Matteucci · 1995 [cited by applicant]
US 5446137A · Maag et al. · 1995 [cited by applicant]
US 5453496A · Caruthers et al. · 1995 [cited by applicant]
US 5455233A · Spielvogel et al. · 1995 [cited by applicant]
US 5457187A · Gmelner et al. · 1995 [cited by applicant]
US 5457191A · Cook et al. · 1995 [cited by applicant]
US 5459255A · Cook et al. · 1995 [cited by applicant]
US 5466677A · Baxter et al. · 1995 [cited by applicant]
US 5466786A · Burh et al. · 1995 [cited by applicant]
US 5470967A · Huie 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 5491133A · Walder 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 Ness et al. · 1996 [cited by applicant]
US 5519126A · Hecht · 1996 [cited by applicant]
US 5519134A · Acevedo et al. · 1996 [cited by applicant]
US 5525711A · Hawkins et al. · 1996 [cited by applicant]
US 5527899A · Froehler · 1996 [cited by applicant]
US 5536821A · Agrawal et al. · 1996 [cited by applicant]
US 5541306A · Agrawal et al. · 1996 [cited by applicant]
US 5541307A · Cook et al. · 1996 [cited by applicant]
US 5550111A · Suhadolnik et al. · 1996 [cited by applicant]
US 5552540A · Haralambidis · 1996 [cited by applicant]
US 5561225A · Maddry et al. · 1996 [cited by applicant]
US 5563253A · Agrawal et al. · 1996 [cited by applicant]
US 5565350A · Kmiec · 1996 [cited by applicant]
US 5565555A · Froehler et al. · 1996 [cited by applicant]
US 5567811A · Mistura et al. · 1996 [cited by applicant]
US 5571799A · Tkachuk et al. · 1996 [cited by applicant]
US 5576427A · Cook et al. · 1996 [cited by applicant]
US 5587361A · Cook et al. · 1996 [cited by applicant]
US 5587469A · Cook et al. · 1996 [cited by applicant]
US 5587470A · 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 5596086A · Matteucci · 1997 [cited by applicant]
US 5596091A · Switzer · 1997 [cited by applicant]
US 5597909A · Urdea et al. · 1997 [cited by applicant]
US 5602240A · De Mesmaeker et al. · 1997 [cited by applicant]
US 5608046A · Cook 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 5618704A · Sanghvi et al. · 1997 [cited by applicant]
US 5623065A · Cook et al. · 1997 [cited by applicant]
US 5623070A · 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 5633360A · Bishofberger 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 5646269A · Matteucci · 1997 [cited by applicant]
US 5652355A · Metelev et al. · 1997 [cited by applicant]
US 5652356A · Agrawal · 1997 [cited by applicant]
US 5663312A · Chaturvedula · 1997 [cited by applicant]
US 5670633A · Cook et al. · 1997 [cited by applicant]
US 5672697A · Buhr et al. · 1997 [cited by applicant]
US 5677437A · Teng et al. · 1997 [cited by applicant]
US 5677439A · Weis 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 5700922A · Cook · 1997 [cited by applicant]
US 5721218A · Froehler · 1998 [cited by applicant]
US 5750692A · Cook et al. · 1998 [cited by applicant]
US 5763588A · Matteucci et al. · 1998 [cited by applicant]
US 5792608A · Swaminathan et al. · 1998 [cited by applicant]
US 5792847A · Burh et al. · 1998 [cited by applicant]
US 5801154A · Baracchini et al. · 1998 [cited by applicant]
US 5808027A · Cook et al. · 1998 [cited by applicant]
US 5830653A · Froehler et al. · 1998 [cited by applicant]
US 5840491A · Kakizuka · 1998 [cited by applicant]
US 5859221A · Cook et al. · 1999 [cited by applicant]
US 5945290A · Cowsert et al. · 1999 [cited by applicant]
US 5948903A · Cook et al. · 1999 [cited by applicant]
US 5994517A · Ts'O · 1999 [cited by applicant]
US 6005087A · Cook et al. · 1999 [cited by applicant]
US 6005096A · Matteucci et al. · 1999 [cited by applicant]
US 6166199A · Cook et al. · 2000 [cited by applicant]
US 6255051B1 · Hammond et al. · 2001 [cited by applicant]
US 6300319B1 · Manoharan · 2001 [cited by applicant]
US 6426220B1 · Bennett et al. · 2002 [cited by applicant]
US 6525191B1 · Ramasamy · 2003 [cited by applicant]
US 6531584B1 · Cook et al. · 2003 [cited by applicant]
US 6582908B2 · Fodor et al. · 2003 [cited by applicant]
US 6600032B1 · Manoharan et al. · 2003 [cited by applicant]
US 6660720B2 · Manoharan · 2003 [cited by applicant]
US 6770748B2 · Imanishi et al. · 2004 [cited by applicant]
US 7015315B1 · Cook et al. · 2006 [cited by applicant]
US 7053207B2 · Wengel et al. · 2006 [cited by applicant]
US 7101993B1 · Cook et al. · 2006 [cited by applicant]
US 7250289B2 · Zhou · 2007 [cited by applicant]
US 7262177B2 · Ts'o et al. · 2007 [cited by applicant]
US 7399845B2 · Seth et al. · 2008 [cited by applicant]
US 7427672B2 · Imanishi et al. · 2008 [cited by applicant]
US 7491805B2 · Vargeese et al. · 2009 [cited by applicant]
US 7547684B2 · Seth et al. · 2009 [cited by applicant]
US 7569686B1 · Bhat et al. · 2009 [cited by applicant]
US 7666854B2 · Seth et al. · 2010 [cited by applicant]
US 7696345B2 · Allerson et al. · 2010 [cited by applicant]
US 7723509B2 · Manoharan et al. · 2010 [cited by applicant]
US 7741457B2 · Swayze et al. · 2010 [cited by applicant]
US 7750131B2 · Seth et al. · 2010 [cited by applicant]
US 7834170B2 · Khvorova et al. · 2010 [cited by applicant]
US 7875733B2 · Bhat et al. · 2011 [cited by applicant]
US 7939677B2 · Bhat et al. · 2011 [cited by applicant]
US 8022193B2 · Swayze et al. · 2011 [cited by applicant]
US 8030467B2 · Seth et al. · 2011 [cited by applicant]
US 8080644B2 · Wengel et al. · 2011 [cited by applicant]
US 8088746B2 · Seth et al. · 2012 [cited by applicant]
US 8088904B2 · Swayze et al. · 2012 [cited by applicant]
US 8106022B2 · Manoharan et al. · 2012 [cited by applicant]
US 8124745B2 · Allerson et al. · 2012 [cited by applicant]
US 8153365B2 · Wengel et al. · 2012 [cited by applicant]
US 8178503B2 · Rigoutsos et al. · 2012 [cited by applicant]
US 8263760B2 · De Kimpe et al. · 2012 [cited by applicant]
US 8268980B2 · Seth et al. · 2012 [cited by applicant]
US 8278283B2 · Seth et al. · 2012 [cited by applicant]
US 8278425B2 · Prakash et al. · 2012 [cited by applicant]
US 8278426B2 · Seth et al. · 2012 [cited by applicant]
US 8329890B2 · Davidson et al. · 2012 [cited by applicant]
US 8440803B2 · Swayze et al. · 2013 [cited by applicant]
US 8501805B2 · Seth et al. · 2013 [cited by applicant]
US 8530640B2 · Seth et al. · 2013 [cited by applicant]
US 8546556B2 · Seth et al. · 2013 [cited by applicant]
US RE44779E · Imanishi et al. · 2014 [cited by applicant]
US 8779116B2 · Davidson et al. · 2014 [cited by applicant]
US 8828956B2 · Manoharan et al. · 2014 [cited by applicant]
US 8901095B2 · Corey et al. · 2014 [cited by applicant]
US 9005906B2 · Swayze et al. · 2015 [cited by applicant]
US 9012421B2 · Migawa et al. · 2015 [cited by applicant]
US 9127276B2 · Prakash et al. · 2015 [cited by applicant]
US 9290760B2 · Rajeev et al. · 2016 [cited by applicant]
US 9340785B2 · Corey et al. · 2016 [cited by applicant]
US 9487779B2 · Davidson et al. · 2016 [cited by applicant]
US 9574191B2 · Corey et al. · 2017 [cited by applicant]
US 9976138B2 · Prakash et al. · 2018 [cited by applicant]
US 10041074B2 · Ozsolak · 2018 [cited by applicant]
US 10364432B2 · Van Roon-Mom et al. · 2019 [cited by applicant]
US 10533175B2 · Rigo et al. · 2020 [cited by applicant]
US 11434488B2 · Freier · 2022 [cited by applicant]
US 11583548B2 · Freier · 2023 [cited by applicant]
US 12350285B2 · Freier et al. · 2025 [cited by applicant]
US 20010053519A1 · Fodor et al. · 2001 [cited by applicant]
US 20030158403A1 · Manoharan et al. · 2003 [cited by applicant]
US 20030175906A1 · Manoharan 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 20040241651A1 · Olek et al. · 2004 [cited by applicant]
US 20050130923A1 · Bhat et al. · 2005 [cited by applicant]
US 20050244851A1 · Blume et al. · 2005 [cited by applicant]
US 20050272080A1 · Palma et al. · 2005 [cited by applicant]
US 20060148740A1 · Platenburg · 2006 [cited by applicant]
US 20070031844A1 · Khvorova et al. · 2007 [cited by applicant]
US 20080039618A1 · Allerson et al. · 2008 [cited by applicant]
US 20100190837A1 · Migawa et al. · 2010 [cited by applicant]
US 20100197762A1 · Swayze et al. · 2010 [cited by applicant]
US 20110178283A1 · Rigoutsos et al. · 2011 [cited by applicant]
US 20110190222A1 · Corey et al. · 2011 [cited by applicant]
US 20130130378A1 · Manoharan et al. · 2013 [cited by applicant]
US 20130198877A1 · Van Roon-Mom et al. · 2013 [cited by applicant]
US 20130225659A1 · Bennett · 2013 [cited by applicant]
US 20140039037A1 · Roon-Mom et al. · 2014 [cited by applicant]
US 20140107330A1 · Freier et al. · 2014 [cited by applicant]
US 20150018540A1 · Prakash et al. · 2015 [cited by applicant]
US 20150184153A1 · Freier et al. · 2015 [cited by applicant]
US 20150191727A1 · Migawa et al. · 2015 [cited by applicant]
US 20150211006A1 · Butler et al. · 2015 [cited by applicant]
US 20150267195A1 · Seth et al. · 2015 [cited by applicant]
US 20150267197A1 · Bennett et al. · 2015 [cited by applicant]
US 20150275212A1 · Albaek et al. · 2015 [cited by applicant]
US 20150315595A1 · Uzcategui et al. · 2015 [cited by applicant]
US 20160159846A1 · Prakash et al. · 2016 [cited by applicant]
US 20160237429A1 · Cubillos-Ruiz et al. · 2016 [cited by applicant]
US 20180258425A1 · Rigo et al. · 2018 [cited by applicant]
US 20190247420A1 · Freier et al. · 2019 [cited by applicant]
US 20220064637A1 · Freier · 2022 [cited by applicant]
US 20230235323A1 · Freier · 2023 [cited by applicant]
US 20240082291A1 · Freier et al. · 2024 [cited by applicant]
JP 2011125219 · 2011 [cited by applicant]
WO WO2002058626 · 2002 [cited by applicant]
WO WO2004013280 · 2004 [cited by applicant]
WO WO2004045543 · 2004 [cited by applicant]
WO WO2004058940 · 2004 [cited by applicant]
WO WO2006006948 · 2006 [cited by applicant]
WO WO2008021149 · 2008 [cited by applicant]
WO WO2010014592 · 2010 [cited by applicant]
WO WO2011097388 · 2011 [cited by applicant]
WO WO2011097614 · 2011 [cited by applicant]
WO WO2011097643 · 2011 [cited by applicant]
WO WO2012012467 · 2012 [cited by applicant]
WO WO2012018257 · 2012 [cited by applicant]
WO WO2013033223 · 2013 [cited by applicant]
WO WO2013138353 · 2013 [cited by applicant]
WO WO2013173635 · 2013 [cited by applicant]
WO WO2013173637 · 2013 [cited by applicant]
WO WO2015017675 · 2015 [cited by applicant]
WO WO2015053624 · 2015 [cited by applicant]
WO WO2015089351 · 2015 [cited by applicant]
WO WO2015143246 · 2015 [cited by applicant]
WO WO2017053781 · 2017 [cited by applicant]
WO WO2018002886 · 2018 [cited by applicant]
WO WO2018089805 · 2018 [cited by applicant]
WO WO2019217708 · 2019 [cited by applicant]
WO WO2020172559 · 2020 [cited by applicant]
WO WO2020245233 · 2020 [cited by applicant]
Alves et al., “Allele-Specific RNA Silencing of Mutant Ataxin-3 Mediates Neuroprotection in a Rat Model of Machado-Joseph Disease” PLoS ONE (2008) 3(10):e3341. [cited by applicant]
Alves et al., “Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3?” Hum. Mol. Gen. (2010) 19(12): 2380-2394. [cited by applicant]
Branch et al., “A good antisense molecule is hard to find,” TIBS (1998) 23:45-50. [cited by applicant]
Chin “On the Preparation and Utilization of Isolated and Purified Oligonucleotides” Document purportedly located on a CD-ROM and contributed to the public collection of the Katherine R. Everett Law Library of the Univer… [cited by applicant]
Costa et al., “Toward RNAi therapy for the polyglutamine disease Machado-Joseph disease” Mol Ther (2013) 21: 1898-1908. [cited by applicant]
Crooke et al., “Basic Principles of Antisense Therapeutics” Antisense Research and Application (1998) Chapter 1:1-50. [cited by applicant]
Crooke, St., et al., “Antisense Drug Technology” Second Edition, CRC Press (2008) Chapters 1-28. [cited by applicant]
Egli, et al., “Synthesis, improved antisense activity and structural rationale for the divergent RNA affinities of 3′-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides.” J Am Chem (2011) 133(41):… [cited by applicant]
Evers et al., “Ataxin-3 Protein and RNA Toxicity in Spinocerebellar Ataxia Type 3: Current Insights and Emerging Therapeutic Strategies.” Mol Neurobiol (2014) 49:1513-1531. [cited by applicant]
Evers et al., “Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: Removal of the CAG containing exon” Neurobiloby of Disease (2013) 58: 49-56. [cited by applicant]
Extended EP Search report for 17869883.3 dated Jul. 16, 2020. [cited by applicant]
Extended EP Search report for 19799466.8 dated Jan. 14, 2022. [cited by applicant]
Fiszer et al., “Oligonucleotide-based strategies to combat polyglutamine diseases” Nucleic Acids Res (2014) 42: 6787-6810. [cited by applicant]
Gautschi et al., “Activity of a novel bel-2/bcl-xLbispecific antisense oligonucleotide against tumors of diverse histologic origins” J. Natl. Cancer Inst. (2001) 93:463-471. [cited by applicant]
GenBank Accession No. NM_004993.5 (downloaded Sep. 18, 2019). [cited by applicant]
Hu et al., “Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs.” Nat. Biotech. (2009) 27(5): 478-484. [cited by applicant]
Hu et al., Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs. Biol. Chem. (2011) 392(4): 315-325. [cited by applicant]
Hu et al., “Allele-selective inhibition of huntingtin expression by switching to an miRNA-like RNAi mechanism” Chem Biol (2010) 17(11): 1183-1188. [cited by applicant]
International Search Report for PCT/US17/61121 dated Apr. 26, 2018. [cited by applicant]
International Search Report for PCT/US19/031562 dated Sep. 17, 2019. [cited by applicant]
International Search Report for PCT/US20/019272 dated Jul. 1, 2020. [cited by applicant]
Kawaguchi et al., “CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1.” Nat. Genet. (1994) 8(3): 221-228. [cited by applicant]
Kenski et al., “siRNA-optimized Modifications for Enhanced In Vivo Activity” Mol Ther Nucleic Acids (2012) 1-8. [cited by applicant]
Liu et al., “ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy.” Nucleic Acids Res. (2013) 41(20): 9570-9583. [cited by applicant]
Maher et al., “Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylpbosphonates in a cell-free system” Nucl. Acid. Res. (1988) 16(8):3341-3358. [cited by applicant]
Mcloughlin et al., “Oligonucleotide therapy mitigates disease in Spinocerebellar Ataxia Type 3 mice.” Annals of Neurology (2018) Accepted Article online Jun. 16, 2018, pp. 1-25. [cited by applicant]
Miller et al., “Allele-specific silencing of dominant disease genes.” PNAS (2003) 100(12): 7195-7200. [cited by applicant]
Moore et al, “Evaluation of Antisense Oligonucleotides Targeting ATXN3 in SCA3 Mouse Models” Molecual Therapy:Nucliec Acids (2017) 7:200-210. [cited by applicant]
Moore et al, “Widespread In vivo suppression of mutant ATXN3 by antisense oligonucleotides in transgenic mouse models of SCA3” Society for Neuroscience 2016 Neuroscience meeting, San Diego, CA, Retreievd from the intern… [cited by applicant]
Moore et al, “Widespread In vivo suppression of mutant ATXN3 by antisense oligonucleotides in transgenic mouse models of SCA3” Society for Neuroscience 2016 Neuroscience meeting, San Diego, CA, Poster Presentation Nov. … [cited by applicant]
New England Biolabs 1998/99 Catalog (cover page and pp. 121 and 284). [cited by applicant]
Partial Search Report for 16849742.8 dated Mar. 14, 2019. [cited by applicant]
Partial Search Report for 17869883.3 dated Apr. 24, 2020. [cited by applicant]
Reynolds et al., “Rational siRNA design for RNA interference” Nature Biotechnology (2004) 22(3):326-330. [cited by applicant]
Riess, et al., “SCA:3 Neurological features, patholgenesis and animal models.” The Cerebellum (2008) 7:125-137. [cited by applicant]
Rodriguez-Lebron et al., “Silencing mutant ATXN3 expression resolves molecular phenotypes in SCA3 transgenic mice.” Mol. Ther. (2013) 21(10): 1909-1918. [cited by applicant]
Sanghvi et al., “Heterocyclic Base Modifications in Nucleic Acids and Their Applications in Antisense Oligonucleotides” Antisense Research and Applications (1993) pp. 273-288. [cited by applicant]
Seidel et al., “Axonal inclusions in spinocerebellar ataxia type 3.” Acta Neuropathol (2010) 120:449-460. [cited by applicant]
Seth et al., “Short Antisense Oligonucleotides with Novel 2′-4′ Conformationaly Restricted Nucleoside Analogues Show Improved Potency Without Increased Toxicity in Animals.” J Med Chem (2009) 52:10-13. [cited by applicant]
Toonen et al., “Antisense Oligonucleotide-Mediated Removal of the Polyglutamine Repeat in Spinocerebellar Ataxia Type 3 Mice” Mol Ther Nucleic Acids (2017) 8:232-242. [cited by applicant]
Toonen et al., “Ataxin-3 exon skipping as a treatment strategy for Spinocerebellar Ataxia type 3” Oligonucleotide Therapeutics Society 2015 Annual Meeting, Leiden, The Netherlands, Poster Presentaiton, Oct. 11, 2015. [cited by applicant]
Ward et al., “Ataxin-3, DAN damage repair, and SCA3 cerebellar degeneration: on the path to parsimony?” PLoS Genet (2015) 11(1):e1004937(1-4). [cited by applicant]
Woolf et al., “Specificity of antisense oligonucleotides in vivo” PNAS (1992) 89: 7305-7309. [cited by applicant]
Yu et al., “Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression” Cell (2012) 150(5): 895-908. [cited by applicant]
Partial Search Report for 20758529.0 dated Dec. 22, 2022. [cited by applicant]
Extended EP Search Report for 20758529.0 dated Mar. 23, 2023. [cited by applicant]