IP Library › Granted Patent US 12,201,677
Granted Patent B2
US 12,201,677 · App. 17/094,327 · Granted Jan 21, 2025

Messenger RNA therapy for the treatment of ornithine transcarbamylase deficiency

Inventors: Frank DeRosa (Lexington, MA); Michael Heartlein (Lexington, MA); Lianne Smith (Lexington, MA); Shrirang Karve (Lexington, MA)
Assignee: TRANSLATE BIO, INC.
A61K38/45A61K9/0019A61K9/1272A61K48/0058C12N9/1018C12Y201/03003A61K48/00
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Quick Facts
Patent No.
US 12,201,677
App. No.
17/094,327
Granted
Jan 21, 2025
Kind
B2
Abstract

The present invention provides, among other things, methods of treating ornithine transcarbamylase (OTC) deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase (OTC) protein at an effective dose and an administration interval such that at least one symptom or feature of the OTC deficiency is reduced in intensity, severity, or frequency or has delayed onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Claims (24)

1. A pharmaceutical composition for treating ornithine transcarbamylase (OTC) deficiency, comprising an mRNA encoding an ornithine transcarbyamylase (OTC) protein and wherein the mRNA encoding the OTC protein comprises a polynucleotide sequence at least 80% identical to SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10, wherein the mRNA encoding the OTC protein is codon optimized, and wherein the OTC protein encoded by the mRNA that is at least 80% identical to SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 10 comprises an amino acid sequence at least 98% identical to SEQ ID NO: 5.

2. A pharmaceutical composition for treating ornithine transcarbamylase (OTC) deficiency, comprising an mRNA encoding an ornithine transcarbyamylase (OTC) protein, wherein the mRNA comprises a polynucleotide sequence at least 85% identical to SEQ ID NO: 7, wherein the mRNA encoding the OTC protein is codon optimized, and wherein the OTC protein encoded by the mRNA that is at least 85% identical to SEQ ID NO: 7 comprises an amino acid sequence at least 98% identical to SEQ ID NO: 5.

3. The composition of claim 1 , wherein the mRNA further comprises a 5′ untranslated region (UTR) sequence of SEQ ID NO: 11.

4. The composition of claim 1 , wherein the mRNA further comprises a 3′ untranslated region (UTR) sequence of SEQ ID NO: 12 or SEQ ID NO: 13.

5. The composition of claim 1 , wherein the mRNA is encapsulated within a liposome.

6. The composition of claim 5 , wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

7. The composition of claim 6 , wherein the one or more cationic lipids comprise a cationic lipid selected from the group consisting of C12-200, MC3, DLinDMA, DLinkC2DMA, cKK-E12, ICE (Imidazole-based), HGT5000, HGT5001, OF-02, DODAC, DDAB, DMRIE, DOSPA, DOGS, DODAP, DODMA and DMDMA, DODAC, DLenDMA, DMRIE, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, DLinDAP, DLincarbDAP, DLinCDAP, KLin-K-DMA, DLin-K-XTC2-DMA, HGT4003, and combinations thereof.

8. The composition of claim 6 , wherein the one or more non-cationic lipids are selected from the group consisting of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), DOPE (1,2-dioleyl-sn-glycero-3-phosphoethanolamine), DOPC (1,2-dioleyl-sn-glycero-3-phosphotidylcholine) DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine), DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine), DOPG (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)) and combinations thereof.

9. The composition of claim 6 , wherein the one or more cholesterol-based lipids are cholesterol and/or PEGylated cholesterol.

10. The composition of claim 5 , wherein the liposome has a size less than about 100 nm.

11. The composition of claim 1 , wherein the mRNA comprises one or more modified nucleotides.

12. The composition of claim 1 , wherein the mRNA is unmodified.

13. The composition of claim 2 , wherein the mRNA further comprises a 5′ untranslated region (UTR) sequence of SEQ ID NO: 11.

14. The composition of claim 2 , wherein the mRNA further comprises a 3′ untranslated region (UTR) sequence of SEQ ID NO: 12 or SEQ ID NO: 13.

15. The composition of claim 14 , wherein the mRNA is encapsulated within a liposome.

16. The composition of claim 15 , wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

17. The composition of claim 16 , wherein the one or more cationic lipids comprise a cationic lipid selected from the group consisting of C12-200, MC3, DLinDMA, DLinkC2DMA, cKK-E12, ICE (Imidazole-based), HGT5000, HGT5001, OF-02, DODAC, DDAB, DMRIE, DOSPA, DOGS, DODAP, DODMA and DMDMA, DODAC, DLenDMA, DMRIE, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, DLinDAP, DLincarbDAP, DLinCDAP, KLin-K-DMA, DLin-K-XTC2-DMA, HGT4003, and combinations thereof.

18. The composition of claim 16 , wherein the one or more non-cationic lipids are selected from the group consisting of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), DOPE (1,2-dioleyl-sn-glycero-3-phosphoethanolamine), DOPC (1,2-dioleyl-sn-glycero-3-phosphotidylcholine) DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine), DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine), DOPG (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)) and combinations thereof.

19. The composition of claim 16 , wherein the one or more cholesterol-based lipids are cholesterol and/or PEGylated cholesterol.

20. The composition of claim 15 , wherein the liposome has a size less than about 100 nm.

21. The composition of claim 2 , wherein the mRNA comprises one or more modified nucleotides.

22. The composition of claim 2 , wherein the mRNA is unmodified.

23. The composition of claim 2 , wherein the mRNA comprises a polynucleotide sequence at least 90% identical to SEQ ID NO:7.

24. The composition of claim 2 , wherein the mRNA comprises a polynucleotide sequence at least 95% identical to SEQ ID NO:7.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 11, 2021
From: DEROSA, FRANK; HEARTLEIN, MICHAEL; SMITH, LIANNE; KARVE, SHRIRANG
To: TRANSLATE BIO MA, INC.
Reel/Frame 055228/0649 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 11, 2021
From: TRANSLATE BIO MA, INC.
To: TRANSLATE BIO, INC.
Reel/Frame 055228/0675 →
Continuity (4)
Division 15621616 · Jun 13, 2017
Provisional Application 62509568 · May 22, 2017
Provisional Application 62349331 · Jun 13, 2016
Related Publication 20210205421A1 · Jul 8, 2021
References Cited (301)
US 5705385A · Bally et al. · 1998 [cited by applicant]
US 5976567A · Wheeler · 1999 [cited by applicant]
US 5981501A · Wheeler et al. · 1999 [cited by applicant]
US 6534484B1 · Wheeler et al. · 2003 [cited by applicant]
US 6815432B2 · Wheeler et al. · 2004 [cited by applicant]
US 7422902B1 · Wheeler et al. · 2008 [cited by applicant]
US 7745651B2 · Heyes et al. · 2010 [cited by applicant]
US 7799565B2 · MacLachlan et al. · 2010 [cited by applicant]
US 7803397B2 · Heyes et al. · 2010 [cited by applicant]
US 7901708B2 · MacLachlan et al. · 2011 [cited by applicant]
US 8101741B2 · MacLachlan et al. · 2012 [cited by applicant]
US 8188263B2 · MacLachlan et al. · 2012 [cited by applicant]
US 8236943B2 · Lee et al. · 2012 [cited by applicant]
US 8329070B2 · MacLachlan et al. · 2012 [cited by applicant]
US 8513403B2 · MacLachlan et al. · 2013 [cited by applicant]
US 8569256B2 · Heyes et al. · 2013 [cited by applicant]
US 8710200B2 · Schrum et al. · 2014 [cited by applicant]
US 8822663B2 · Schrum et al. · 2014 [cited by applicant]
US 8883202B2 · Manoharan et al. · 2014 [cited by applicant]
US 8980864B2 · Hoge et al. · 2015 [cited by applicant]
US 9051567B2 · Fitzgerald et al. · 2015 [cited by applicant]
US 9061059B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9089604B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9095552B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9107886B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9114113B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9181319B2 · Schrum et al. · 2015 [cited by applicant]
US 9186325B2 · Manoharan et al. · 2015 [cited by applicant]
US 9186372B2 · de Fougerolles et al. · 2015 [cited by applicant]
US 9187748B2 · Geisbert et al. · 2015 [cited by applicant]
US 9192651B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9220755B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9220792B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9233141B2 · Chakraborty et al. · 2016 [cited by applicant]
US 9254311B2 · Bancel et al. · 2016 [cited by applicant]
US 9295689B2 · de Fougerolles et al. · 2016 [cited by applicant]
US 9301993B2 · Chakraborty et al. · 2016 [cited by applicant]
US 9303079B2 · Chakraborty et al. · 2016 [cited by applicant]
US 9334328B2 · Schrum et al. · 2016 [cited by applicant]
US 9345780B2 · Manoharan et al. · 2016 [cited by applicant]
US 9352042B2 · Heyes et al. · 2016 [cited by applicant]
US 9352048B2 · Manoharan et al. · 2016 [cited by applicant]
US 9364435B2 · Yaworski et al. · 2016 [cited by applicant]
US 9394234B2 · Chen et al. · 2016 [cited by applicant]
US 9404127B2 · Yaworski et al. · 2016 [cited by applicant]
US 9428535B2 · de Fougerolles et al. · 2016 [cited by applicant]
US 9428751B2 · MacDonald et al. · 2016 [cited by applicant]
US 9447164B2 · Schrum et al. · 2016 [cited by applicant]
US 9464124B2 · Bancel et al. · 2016 [cited by applicant]
US 9492386B2 · MacLachlan et al. · 2016 [cited by applicant]
US 9504651B2 · MacLachlan et al. · 2016 [cited by applicant]
US 9504734B2 · Bancel et al. · 2016 [cited by applicant]
US 9518272B2 · Yaworksi et al. · 2016 [cited by applicant]
US 9572874B2 · Fotin-Mleczek et al. · 2017 [cited by applicant]
US 9572896B2 · Bancel et al. · 2017 [cited by applicant]
US 9572897B2 · Bancel et al. · 2017 [cited by applicant]
US 9587003B2 · Bancel et al. · 2017 [cited by applicant]
US 9616084B2 · Mutzke · 2017 [cited by applicant]
US 9623095B2 · Kallen et al. · 2017 [cited by applicant]
US D787703S · Mayer · 2017 [cited by applicant]
US 9636301B2 · Weber · 2017 [cited by applicant]
US 9655955B2 · Hoerr et al. · 2017 [cited by applicant]
US 9657295B2 · Schrum et al. · 2017 [cited by applicant]
US 9669089B2 · Thess et al. · 2017 [cited by applicant]
US 9670152B2 · Payne et al. · 2017 [cited by applicant]
US 9675668B2 · Bancel et al. · 2017 [cited by applicant]
US 9682139B2 · Monoharan et al. · 2017 [cited by applicant]
US 9683233B2 · Thess · 2017 [cited by applicant]
US 9687550B2 · Manoharan et al. · 2017 [cited by applicant]
US 9688729B2 · Kramps et al. · 2017 [cited by applicant]
US 20020192651A1 · Wheeler et al. · 2002 [cited by applicant]
US 20030181410A1 · Wheeler et al. · 2003 [cited by applicant]
US 20040142025A1 · MacLachlan et al. · 2004 [cited by applicant]
US 20060008910A1 · MacLachlan et al. · 2006 [cited by applicant]
US 20060083780A1 · Heyes et al. · 2006 [cited by applicant]
US 20070135372A1 · MacLachlan et al. · 2007 [cited by applicant]
US 20090270481A1 · MacLachlan et al. · 2009 [cited by applicant]
US 20100041152A1 · Wheeler et al. · 2010 [cited by applicant]
US 20110244026A1 · Guild et al. · 2011 [cited by applicant]
US 20110311583A1 · Manoharan et al. · 2011 [cited by applicant]
US 20120065252A1 · Schrum et al. · 2012 [cited by applicant]
US 20120128760A1 · Manoharan et al. · 2012 [cited by applicant]
US 20120142756A1 · Guild et al. · 2012 [cited by applicant]
US 20120202871A1 · Heyes et al. · 2012 [cited by applicant]
US 20120237975A1 · Schrum et al. · 2012 [cited by applicant]
US 20120251618A1 · Schrum et al. · 2012 [cited by applicant]
US 20120328668A1 · MacLachlan et al. · 2012 [cited by applicant]
US 20130195967A1 · Guild et al. · 2013 [cited by applicant]
US 20130237594A1 · de Fougerolles et al. · 2013 [cited by applicant]
US 20130259923A1 · Bancel et al. · 2013 [cited by applicant]
US 20130259924A1 · Bancel et al. · 2013 [cited by applicant]
US 20130266640A1 · de Fougerolles et al. · 2013 [cited by applicant]
US 20140010861A1 · Bancel et al. · 2014 [cited by applicant]
US 20140044772A1 · MacLachlan et al. · 2014 [cited by applicant]
US 20140105964A1 · Bancel et al. · 2014 [cited by applicant]
US 20140105965A1 · Bancel et al. · 2014 [cited by applicant]
US 20140147432A1 · Bancel et al. · 2014 [cited by applicant]
US 20140147454A1 · Chakraborty et al. · 2014 [cited by applicant]
US 20140148502A1 · Bancel et al. · 2014 [cited by applicant]
US 20140155472A1 · Bancel et al. · 2014 [cited by applicant]
US 20140155473A1 · Bancel et al. · 2014 [cited by applicant]
US 20140155474A1 · Bancel et al. · 2014 [cited by applicant]
US 20140155475A1 · Bancel et al. · 2014 [cited by applicant]
US 20140171485A1 · Bancel et al. · 2014 [cited by applicant]
US 20140179756A1 · MacLachlan et al. · 2014 [cited by applicant]
US 20140179771A1 · Bancel et al. · 2014 [cited by applicant]
US 20140186432A1 · Bancel et al. · 2014 [cited by applicant]
US 20140193482A1 · Bancel et al. · 2014 [cited by applicant]
US 20140194494A1 · Bancel et al. · 2014 [cited by applicant]
US 20140199371A1 · Bancel et al. · 2014 [cited by applicant]
US 20140200261A1 · Hoge et al. · 2014 [cited by applicant]
US 20140200262A1 · Bancel et al. · 2014 [cited by applicant]
US 20140200263A1 · Bancel et al. · 2014 [cited by applicant]
US 20140200264A1 · Bancel et al. · 2014 [cited by applicant]
US 20140206752A1 · Afeyan et al. · 2014 [cited by applicant]
US 20140206753A1 · Guild et al. · 2014 [cited by applicant]
US 20140206755A1 · Bancel et al. · 2014 [cited by applicant]
US 20140206852A1 · Hoge et al. · 2014 [cited by applicant]
US 20140221465A1 · Bancel et al. · 2014 [cited by applicant]
US 20140243399A1 · Schrum et al. · 2014 [cited by applicant]
US 20140249208A1 · Bancel et al. · 2014 [cited by applicant]
US 20140255467A1 · Bancel et al. · 2014 [cited by applicant]
US 20140255468A1 · Bancel et al. · 2014 [cited by applicant]
US 20140275227A1 · Hoge et al. · 2014 [cited by applicant]
US 20140275229A1 · Bancel et al. · 2014 [cited by applicant]
US 20140294937A1 · MacLachlan et al. · 2014 [cited by applicant]
US 20140343129A1 · de Fougerolles et al. · 2014 [cited by applicant]
US 20150005372A1 · Hoge et al. · 2015 [cited by applicant]
US 20150017211A1 · de Fougerolles et al. · 2015 [cited by applicant]
US 20150044277A1 · Bancel et al. · 2015 [cited by applicant]
US 20150050354A1 · Bouchon et al. · 2015 [cited by applicant]
US 20150051268A1 · Bancel et al. · 2015 [cited by applicant]
US 20150056253A1 · Bancel et al. · 2015 [cited by applicant]
US 20150064235A1 · Bancel et al. · 2015 [cited by applicant]
US 20150064236A1 · Bancel et al. · 2015 [cited by applicant]
US 20150064242A1 · Heyes et al. · 2015 [cited by applicant]
US 20150064725A1 · Schrum et al. · 2015 [cited by applicant]
US 20150086614A1 · Bancel et al. · 2015 [cited by applicant]
US 20150111248A1 · Bancel et al. · 2015 [cited by applicant]
US 20150111945A1 · Geisbert et al. · 2015 [cited by applicant]
US 20150166465A1 · Chen et al. · 2015 [cited by applicant]
US 20150190515A1 · Manoharan et al. · 2015 [cited by applicant]
US 20150315541A1 · Bancel et al. · 2015 [cited by applicant]
US 20150315584A1 · MacDonald et al. · 2015 [cited by applicant]
US 20150366997A1 · Guild et al. · 2015 [cited by applicant]
US 20160082092A1 · Hoerr et al. · 2016 [cited by applicant]
US 20160089424A1 · Hoerr et al. · 2016 [cited by applicant]
US 20160095924A1 · Hope et al. · 2016 [cited by applicant]
US 20160114011A1 · Bancel et al. · 2016 [cited by applicant]
US 20160115477A1 · MacLachlan et al. · 2016 [cited by applicant]
US 20160115483A1 · MacLachlan et al. · 2016 [cited by applicant]
US 20160136236A1 · Hoge et al. · 2016 [cited by applicant]
US 20160151284A1 · Heyes et al. · 2016 [cited by applicant]
US 20160158385A1 · Bancel et al. · 2016 [cited by applicant]
US 20160193299A1 · de Fougerolles et al. · 2016 [cited by applicant]
US 20160194368A1 · Hoge et al. · 2016 [cited by applicant]
US 20160194625A1 · Hoge et al. · 2016 [cited by applicant]
US 20160199485A1 · Manoharan et al. · 2016 [cited by applicant]
US 20160213785A1 · Manoharan et al. · 2016 [cited by applicant]
US 20160237108A1 · Fraley et al. · 2016 [cited by applicant]
US 20160237134A1 · Hoge et al. · 2016 [cited by applicant]
US 20160250354A1 · Manoharan et al. · 2016 [cited by applicant]
US 20160251681A1 · Yaworski et al. · 2016 [cited by applicant]
US 20160256567A1 · Heyes et al. · 2016 [cited by applicant]
US 20160256568A1 · Heyes et al. · 2016 [cited by applicant]
US 20160256573A1 · de Fougerolles et al. · 2016 [cited by applicant]
US 20160264971A1 · Geisbert et al. · 2016 [cited by applicant]
US 20160264975A1 · Schrum et al. · 2016 [cited by applicant]
US 20160274089A1 · Ciufolini et al. · 2016 [cited by applicant]
US 20160304552A1 · Roy et al. · 2016 [cited by applicant]
US 20160317647A1 · Ciaramella et al. · 2016 [cited by applicant]
US 20160317676A1 · Hope et al. · 2016 [cited by applicant]
US 20160331828A1 · Ciaramella et al. · 2016 [cited by applicant]
US 20160348099A1 · Roy et al. · 2016 [cited by applicant]
US 20160354490A1 · Roy et al. · 2016 [cited by applicant]
US 20160354491A1 · Roy et al. · 2016 [cited by applicant]
US 20160354492A1 · Roy et al. · 2016 [cited by applicant]
US 20160354493A1 · Roy et al. · 2016 [cited by applicant]
US 20160367687A1 · Manoharan et al. · 2016 [cited by applicant]
US 20160367702A1 · Hoge et al. · 2016 [cited by applicant]
US 20160375134A1 · Bancel et al. · 2016 [cited by applicant]
US 20160375137A9 · Manoharan et al. · 2016 [cited by applicant]
US 20170000858A1 · Fotin-Mleczek et al. · 2017 [cited by applicant]
US 20170000870A1 · Hoerr et al. · 2017 [cited by applicant]
US 20170000871A1 · Probst et al. · 2017 [cited by applicant]
US 20170002060A1 · Bolen et al. · 2017 [cited by applicant]
US 20170007702A1 · Heyes et al. · 2017 [cited by applicant]
US 20170014496A1 · Fotin-Mleczek et al. · 2017 [cited by applicant]
US 20170028059A1 · Baumhof et al. · 2017 [cited by applicant]
US 20170029847A1 · Thess · 2017 [cited by applicant]
US 20170042814A1 · Yaworski et al. · 2017 [cited by applicant]
US 20170056528A1 · De Fougerolles et al. · 2017 [cited by applicant]
US 20170056529A1 · Thess et al. · 2017 [cited by applicant]
US 20170065675A1 · Bancel et al. · 2017 [cited by applicant]
US 20170065727A1 · Fotin-Mleczek et al. · 2017 [cited by applicant]
US 20170114378A1 · Wochner et al. · 2017 [cited by applicant]
US 20170128549A1 · Fotin-Mleczek et al. · 2017 [cited by applicant]
US 20170136131A1 · Roy et al. · 2017 [cited by applicant]
US 20170136132A1 · Roy et al. · 2017 [cited by applicant]
US 20170143631A1 · Chen et al. · 2017 [cited by applicant]
US 20170143796A1 · Schrum et al. · 2017 [cited by applicant]
US 20170151333A1 · Heyes et al. · 2017 [cited by applicant]
US 20170157268A1 · Ansell et al. · 2017 [cited by applicant]
US 20170166905A1 · Eberle et al. · 2017 [cited by applicant]
US 20170173128A1 · Hoge et al. · 2017 [cited by applicant]
US 20170175129A1 · Roy et al. · 2017 [cited by applicant]
US 20170182081A1 · Mutzke · 2017 [cited by applicant]
US 20170182150A1 · Kallen et al. · 2017 [cited by applicant]
CA 2807552 · 2012 [cited by applicant]
CN 105658242A · 2016 [cited by applicant]
CN 106164248A · 2016 [cited by applicant]
EP 1519714 · 2010 [cited by applicant]
EP 2449106 · 2012 [cited by applicant]
EP 2338478 · 2013 [cited by applicant]
EP 2823809 · 2015 [cited by applicant]
WO WO2005026372 · 2005 [cited by applicant]
WO WO2005121348A1 · 2005 [cited by applicant]
WO WO2009127060 · 2009 [cited by applicant]
WO WO2010042877A1 · 2010 [cited by applicant]
WO WO2011068810A1 · 2011 [cited by applicant]
WO WO2011141705 · 2011 [cited by applicant]
WO WO2012019168 · 2012 [cited by applicant]
WO WO2012135805 · 2012 [cited by applicant]
WO WO2013039857 · 2013 [cited by applicant]
WO WO2013039861 · 2013 [cited by applicant]
WO WO2013090186A1 · 2013 [cited by applicant]
WO WO2013101690 · 2013 [cited by applicant]
WO WO2013126803 · 2013 [cited by applicant]
WO WO2013130161 · 2013 [cited by applicant]
WO WO2013151663 · 2013 [cited by applicant]
WO WO2013151664 · 2013 [cited by applicant]
WO WO2013151666 · 2013 [cited by applicant]
WO WO2013151667 · 2013 [cited by applicant]
WO WO2013151668 · 2013 [cited by applicant]
WO WO2013151670 · 2013 [cited by applicant]
WO WO2013151671 · 2013 [cited by applicant]
WO WO2013151672 · 2013 [cited by applicant]
WO WO2013151736 · 2013 [cited by applicant]
WO WO2013185069 · 2013 [cited by applicant]
WO WO2014113089 · 2014 [cited by applicant]
WO WO2014144039 · 2014 [cited by applicant]
WO WO2014144711 · 2014 [cited by applicant]
WO WO2014144767 · 2014 [cited by applicant]
WO WO2014152027 · 2014 [cited by applicant]
WO WO2014152030 · 2014 [cited by applicant]
WO WO2014152031 · 2014 [cited by applicant]
WO WO2014152211 · 2014 [cited by applicant]
WO WO2014152540 · 2014 [cited by applicant]
WO WO2014158795 · 2014 [cited by applicant]
WO WO2014159813 · 2014 [cited by applicant]
WO WO2015006747A2 · 2015 [cited by applicant]
WO WO2015051169 · 2015 [cited by applicant]
WO WO2015051173 · 2015 [cited by applicant]
WO WO2015058069 · 2015 [cited by applicant]
WO WO2015048744 · 2015 [cited by applicant]
WO WO2015085318 · 2015 [cited by applicant]
WO WO2015089511 · 2015 [cited by applicant]
WO WO2015164773A1 · 2015 [cited by applicant]
WO WO2015011633 · 2016 [cited by applicant]
WO WO2016054421 · 2016 [cited by applicant]
WO WO2016070166A2 · 2016 [cited by applicant]
WO WO2016071857 · 2016 [cited by applicant]
WO WO2016077123 · 2016 [cited by applicant]
WO WO2016077125 · 2016 [cited by applicant]
WO WO20160706166A2 · 2016 [cited by applicant]
WO WO2016118724 · 2016 [cited by applicant]
WO WO2016118725 · 2016 [cited by applicant]
WO WO2016154127 · 2016 [cited by applicant]
WO WO2016164762 · 2016 [cited by applicant]
WO WO2016183366A2 · 2016 [cited by applicant]
WO WO2016197132A1 · 2016 [cited by applicant]
WO WO2016197133A1 · 2016 [cited by applicant]
WO WO2016201377A1 · 2016 [cited by applicant]
WO WO2017019891A2 · 2017 [cited by applicant]
WO WO2017049074A1 · 2017 [cited by applicant]
WO WO2017049275A2 · 2017 [cited by applicant]
WO WO2017049286A1 · 2017 [cited by applicant]
WO WO2017102010A1 · 2017 [cited by applicant]
WO WO2017103088A1 · 2017 [cited by applicant]
WO WO2017108087A1 · 2017 [cited by applicant]
WO WO2017109134A1 · 2017 [cited by applicant]
WO WO2017109161A1 · 2017 [cited by applicant]
WO WO2019207060A1 · 2019 [cited by applicant]
Cheng et al. “Codon Optimization of Gene Editing CRISPR-SaCas9 Augments Protein Expression in Human Liver Cells to Boost in vivo Therapeutic Application.” The FASEB Journal 33.S1 (2019): 495-3. (Year: 2019). [cited by examiner]
Wang et al. “Preclinical evaluation of a clinical candidate AAV8 vector for ornithine transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting vector genome.”Mol Genet Metab. Feb. 2012;105(2):203… [cited by examiner]
Mauro et al. “A critical analysis of codon optimization in human therapeutics.” Trends Mol Med. Nov. 2014;20(11):604-13. (Year: 2014). [cited by examiner]
Ward et al. “Codon optimization of human factor VIII cDNAs leads to high-level expression.” Blood . Jan. 20, 2011;117(3):798-807. (Year: 2011). [cited by examiner]
Krauss et al. “A cDNA clone for the precursor of rat mitochondrial ornithine transcarbamylase: comparison of rat and human leader sequences and conservation of catalytic sites.” Nucleic Acids Res Feb. 11, 1985;13(3):943… [cited by examiner]
Ye et al. “Differences in the human and mouse amino-terminal leader peptides of ornithine transcarbamylase affect mitochondrial import and efficacy of adenoviral vectors.” Hum Gene Ther . Jun. 10, 2001; 12(9):1035-46. (… [cited by examiner]
U.S. Appl. No. 15/621,616 2018/0008680 U.S. Pat. No. 10,835,583, filed Jun. 13, 2017 Jan. 11, 2018 Nov. 17, 2020, Frank DeRosa, Messenger RNA Therapy for the Treatment of Ornithine Transcarbamylase Deficiency. [cited by applicant]
U.S. Appl. No. 17/094,327 2021/0205421, filed Nov. 10, 2020 Jul. 8, 2021, Frank DeRosa, Messenger RNA Therapy for the Treatment of Ornithine Transcarbamylase Deficiency. [cited by applicant]
Schmitz et al., “Purification of nucleic acids by selective precipitation with polyethelyne glycol 6000”, Analytical Biochemistry, 2006, 354(2): 311-313. [cited by applicant]
Alton et al., “A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis,” Effica… [cited by applicant]
Database EMBL, Database Accession No. BAW43135 (Dec. 5, 2013). [cited by applicant]
International Search Report and Written Opinion for PCT/US17/37237 mailed Aug. 21, 2017, 17 pages. [cited by applicant]
Kowalski et al. “Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery.” Mol Ther. Apr. 10, 2019;27(4): 710-728. (Year: 2019). [cited by applicant]
Matsui et al. “Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases.” Sci Rep. Oct. 28, 2015;5:15810. (Year: 2015). [cited by applicant]
Moscioni et al., “Long-term correction of ammonia metabolism and prolonged survival in ornithine transcarbamylase-deficient mice following liver-directed treatment with adeno-associated viral vectors”, Mol Ther., Jul. 2… [cited by applicant]
Trepotec et al. “Delivery of MRNA Therapeutics for the Treatment of Hepatic Diseases.” Mol Ther. Apr. 10, 2019;27(4): 794-802. (Year: 2019). [cited by applicant]
Wang et al., “Preclinical evaluation of a clinical candidate AAV8 vector for ornithine transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting vector genome”, Mol Genet Metab., Feb. 2012, vol. 1… [cited by applicant]
Wang et al., “Sustained correction of OTC deficiency in spf( ash) mice using optimized self-complementary AAV2/8 vectors”, Gene Ther., Apr. 2012, vol. 19, No. 4, pp. 404-410. [cited by applicant]