Granted Patent
B2
US 12,509,666 · App. 17/830,102 · Granted Dec 30, 2025
MRNA therapy for phenylketonuria
Inventors:
Frank DeRosa (Lexington, MA); Anusha Dias (Lexington, MA); Michael Heartlein (Lexington, MA)
Assignee:
TRANSLATE BIO, INC.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present invention provides, among other things, methods of treating phenylketonuria (PKU), including administering to a subject in need of treatment a composition comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in 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 (21)
1 . A method of treating phenylketonuria (PKU), comprising administering to a subject in need of treatment a composition comprising a codon optimized mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in onset, wherein the mRNA is encapsulated with 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.
2 . The method of claim 1 , wherein the liposome has a size less than about 100 nm.
3 . The method of claim 1 , wherein the mRNA is administered at the effective dose ranging from about 0.1-3.0 mg/kg body weight.
4 . The method of claim 1 , wherein the composition is administered intravenously.
5 . The method of claim 1 , wherein the composition is administered once a week, once every two weeks, twice a month, or once a month.
6 . The method of claim 1 , wherein the administering of the composition results in the expression of the PAH protein detectable in liver, kidney, spleen, muscle, and serum.
7 . The method of claim 1 , wherein the administering of the composition results in reduced phenylalanine level in the serum as compared to the baseline phenylalanine level before the treatment.
8 . The method of claim 7 , wherein the administering of the composition results in reduction of phenylalanine levels to about 1000 μmol/L or less in the serum.
9 . The method of claim 7 , wherein the administering of the composition results in reduction of phenylalanine levels to about 500 μmol/L or less in the serum.
10 . The method of claim 7 , wherein the administering of the composition results in reduction of phenylalanine levels to about 120 μmol/L or less in the serum.
11 . The method of claim 1 , wherein the codon-optimized mRNA comprises a coding sequence at least 90% identical to SEQ ID NO:3, SEQ ID NO:7 or SEQ ID NO: 8.
12 . The method of claim 11 , wherein the codon-optimized mRNA comprises a coding sequence at least 90% identical to SEQ ID NO:3.
13 . The method of claim 11 , wherein the codon-optimized mRNA comprises a coding sequence at least 90% identical to SEQ ID NO:7.
14 . The method of claim 11 , wherein the codon-optimized mRNA comprises a coding sequence at least 90% identical to SEQ ID NO:8.
15 . The method of claim 11 , wherein the codon-optimized mRNA comprises a 5′ UTR sequence of SEQ ID NO:4 and a 3′ UTR sequence of SEQ ID NO:5 or SEQ ID NO:6.
16 . A composition for treating phenylketonuria (PKU), comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose amount encapsulated within 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, wherein the mRNA comprises a coding sequence at least 90% identical to SEQ ID NO:3, SEQ ID NO:7 or SEQ ID NO: 8, a 5′ UTR sequence of SEQ ID NO:4, and a 3′ UTR sequence of SEQ ID NO:5 or SEQ ID NO: 6.
17 . The composition of claim 16 , wherein the liposome comprises cKK-E12, DOPE, cholesterol, and DMG-PEG2K.
18 . The composition of claim 16 , wherein the liposome has a size less than about 100 nm.
19 . The composition of claim 16 , wherein the composition is formulated for intravenous administration.
20 . The composition of claim 16 , wherein the mRNA comprises a coding sequence at least 90% identical to SEQ ID NO:3.
21 . A composition for treating phenylketonuria (PKU), comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose amount encapsulated within a liposome, wherein the mRNA comprises SEQ ID NO:7 or SEQ ID NO:8, and further wherein the liposome comprises one or both of a cationic lipid and a non-cationic lipid, one or more cholesterol-based lipids and one or more PEG-modified lipids.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 3, 2022
From: DEROSA, FRANK; HEARTLEIN, MICHAEL; DIAS, ANUSHA
To: SHIRE HUMAN GENETIC THERAPIES, INC.
Reel/Frame 060098/0578 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 3, 2022
From: SHIRE HUMAN GENETIC THERAPIES, INC.
To: RANA THERAPEUTICS, INC.
Reel/Frame 060268/0773 →
CHANGE OF NAME
Recorded Jun 3, 2022
From: RANA THERAPEUTICS, INC.
To: TRANSLATE BIO, INC.
Reel/Frame 060271/0148 →
Continuity (5)
Provisional Application
61894303
· Oct 22, 2013
References Cited (400)
US 2647121A
· Jacoby
· 1953
[cited by applicant]
US 2717909A
· Kosmin
· 1955
[cited by applicant]
US 2819718A
· Goldman
· 1958
[cited by applicant]
US 2844629A
· William et al.
· 1958
[cited by applicant]
US 5705385A
· Bally et al.
· 1998
[cited by applicant]
US 5885613A
· Holland et al.
· 1999
[cited by applicant]
US 5910168A
· Myers et al.
· 1999
[cited by applicant]
US 5916208A
· Luther et al.
· 1999
[cited by applicant]
US 5965434A
· Wolff et al.
· 1999
[cited by applicant]
US 5976567A
· Wheeler et al.
· 1999
[cited by applicant]
US 5976569A
· Milstein
· 1999
[cited by applicant]
US 5981501A
· Wheeler et al.
· 1999
[cited by applicant]
US 6055454A
· Heemels
· 2000
[cited by applicant]
US 6067471A
· Warren
· 2000
[cited by applicant]
US 6090384A
· Ra et al.
· 2000
[cited by applicant]
US 6096070A
· Ragheb et al.
· 2000
[cited by applicant]
US 6096075A
· Bokros et al.
· 2000
[cited by applicant]
US 6120799A
· McDonald et al.
· 2000
[cited by applicant]
US 6147055A
· Hobart et al.
· 2000
[cited by applicant]
US 6152955A
· KenKniqht et al.
· 2000
[cited by applicant]
US 6165763A
· Brown et al.
· 2000
[cited by applicant]
US 6169923B1
· Kroll
· 2001
[cited by applicant]
US 6176877B1
· Buchanan et al.
· 2001
[cited by applicant]
US 6204297B1
· Tracy et al.
· 2001
[cited by applicant]
US 6210892B1
· Bennett et al.
· 2001
[cited by applicant]
US 6214804B1
· Felaner et al.
· 2001
[cited by applicant]
US 6271208B1
· Bischoff
· 2001
[cited by applicant]
US 6271209B1
· Smith et al.
· 2001
[cited by applicant]
US 6287591B1
· Semple et al.
· 2001
[cited by applicant]
US 6299604B1
· Raaheb et al.
· 2001
[cited by applicant]
US 6335199B1
· Bischoff et al.
· 2002
[cited by applicant]
US 6358278B1
· Brendzel et al.
· 2002
[cited by applicant]
US 6370434B1
· Zhana et al.
· 2002
[cited by applicant]
US 6371983B1
· Lane
· 2002
[cited by applicant]
US 6417326B1
· Cullis et al.
· 2002
[cited by applicant]
US 6485726B1
· Blumberg et al.
· 2002
[cited by applicant]
US 6534484B1
· Wheeler et al.
· 2003
[cited by applicant]
US 6585410B1
· Ryan
· 2003
[cited by applicant]
US 6586410B1
· Wheeler et al.
· 2003
[cited by applicant]
US 6670178B1
· Selden et al.
· 2003
[cited by applicant]
US 6696424B1
· Wheeler
· 2004
[cited by applicant]
US 6733777B2
· Erbacher et al.
· 2004
[cited by applicant]
US 6743823B1
· Summar et al.
· 2004
[cited by applicant]
US 6756055B2
· McDonald et al.
· 2004
[cited by applicant]
US 6790838B2
· Alison et al.
· 2004
[cited by applicant]
US 6815432B2
· Wheeler et al.
· 2004
[cited by applicant]
US 6821530B2
· Koob et al.
· 2004
[cited by applicant]
US 6835395B1
· Semple et al.
· 2004
[cited by applicant]
US 6858224B2
· Wheeler et al.
· 2005
[cited by applicant]
US 6858225B2
· Semple et al.
· 2005
[cited by applicant]
US 6887665B2
· Trulson et al.
· 2005
[cited by applicant]
US 6998115B2
· Anaer et al.
· 2006
[cited by applicant]
US 7022214B2
· Olech
· 2006
[cited by applicant]
US 7067697B2
· Gao
· 2006
[cited by applicant]
US 7084303B2
· Watanabe et al.
· 2006
[cited by applicant]
US 7341738B2
· Semple et al.
· 2008
[cited by applicant]
US 7422902B1
· Wheeler et al.
· 2008
[cited by applicant]
US 7427394B2
· Anderson et al.
· 2008
[cited by applicant]
US 7507859B2
· Grinstaff et al.
· 2009
[cited by applicant]
US 7556684B2
· Bury et al.
· 2009
[cited by applicant]
US 7745651B2
· Maclachlan 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 7972435B2
· Bury et al.
· 2011
[cited by applicant]
US 8021686B2
· Semple et al.
· 2011
[cited by applicant]
US 8071082B2
· Zuaates et al.
· 2011
[cited by applicant]
US 8101741B2
· Maclachlan et al.
· 2012
[cited by applicant]
US 8106022B2
· Manoharan et al.
· 2012
[cited by applicant]
US 8158601B2
· Chen 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 8278036B2
· Kariko et al.
· 2012
[cited by applicant]
US 8287849B2
· Lanaer et al.
· 2012
[cited by applicant]
US 8329070B2
· Maclachlan et al.
· 2012
[cited by applicant]
US 8450298B2
· Mahon et al.
· 2013
[cited by applicant]
US 8450467B2
· Manoharan et al.
· 2013
[cited by applicant]
US 8513403B2
· Maclachlan et al.
· 2013
[cited by applicant]
US 8557231B2
· Lanaer et al.
· 2013
[cited by applicant]
US 8562966B2
· Zuqates et al.
· 2013
[cited by applicant]
US 8569256B2
· Heyes et al.
· 2013
[cited by applicant]
US 8652512B2
· Schmehl et al.
· 2014
[cited by applicant]
US 8691966B2
· Kariko et al.
· 2014
[cited by applicant]
US 8701200B2
· Schrum et al.
· 2014
[cited by applicant]
US 8748089B2
· Kariko et al.
· 2014
[cited by applicant]
US 8802644B2
· Chen et al.
· 2014
[cited by applicant]
US 8808681B2
· Anderson et al.
· 2014
[cited by applicant]
US 8808982B2
· Dahl et al.
· 2014
[cited by applicant]
US 8822663B2
· Schrum et al.
· 2014
[cited by applicant]
US 8828956B2
· Manoharan et al.
· 2014
[cited by applicant]
US 8835108B2
· Kariko et al.
· 2014
[cited by applicant]
US 8846348B2
· Jendrisak et al.
· 2014
[cited by applicant]
US 8853377B2
· Guild et al.
· 2014
[cited by applicant]
US 8859229B2
· Rabinovich et al.
· 2014
[cited by applicant]
US 8883202B2
· Manoharan et al.
· 2014
[cited by applicant]
US 8936942B2
· Heyes et al.
· 2015
[cited by applicant]
US 8969353B2
· Mahon et al.
· 2015
[cited by applicant]
US 8980864B2
· Hoge et al.
· 2015
[cited by applicant]
US 8999351B2
· Manoharan et al.
· 2015
[cited by applicant]
US 8999950B2
· Maclachlan et al.
· 2015
[cited by applicant]
US 9005930B2
· Jendrisak et al.
· 2015
[cited by applicant]
US 9012219B2
· Kariko et al.
· 2015
[cited by applicant]
US 9012498B2
· Manoharan et al.
· 2015
[cited by applicant]
US 9018187B2
· Heyes et al.
· 2015
[cited by applicant]
US 9040256B2
· Grunenwald 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 9074208B2
· Maclachlan et al.
· 2015
[cited by applicant]
US 9080211B2
· Grunenwald et al.
· 2015
[cited by applicant]
US 9085801B2
· Grunenwald 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 9428751B2
· MacDonald 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 9522176B2
· DeRosa et al.
· 2016
[cited by applicant]
US 20020022721A1
· Trulson et al.
· 2002
[cited by applicant]
US 20020094528A1
· Salafsky
· 2002
[cited by applicant]
US 20020192651A1
· Wheeler et al.
· 2002
[cited by applicant]
US 20020192721A1
· Rizzuto et al.
· 2002
[cited by applicant]
US 20020193622A1
· Watanabe et al.
· 2002
[cited by applicant]
US 20030082154A1
· Leamon
· 2003
[cited by applicant]
US 20030083272A1
· Wiederholt et al.
· 2003
[cited by applicant]
US 20030104044A1
· Semple et al.
· 2003
[cited by applicant]
US 20030181410A1
· Wheeler et al.
· 2003
[cited by applicant]
US 20030215395A1
· Yu et al.
· 2003
[cited by applicant]
US 20040110709A1
· Li et al.
· 2004
[cited by applicant]
US 20040132683A1
· Feigner et al.
· 2004
[cited by applicant]
US 20040142025A1
· MacLachlan et al.
· 2004
[cited by applicant]
US 20040224912A1
· Dobie et al.
· 2004
[cited by applicant]
US 20040235982A1
· Rabasca et al.
· 2004
[cited by applicant]
US 20050004058A1
· Benoit et al.
· 2005
[cited by applicant]
US 20050008689A1
· Semple et al.
· 2005
[cited by applicant]
US 20050032730A1
· Von Der Mulbe et al.
· 2005
[cited by applicant]
US 20050054026A1
· Atsushi et al.
· 2005
[cited by applicant]
US 20050059005A1
· Tuschl et al.
· 2005
[cited by applicant]
US 20050059624A1
· Hoerr et al.
· 2005
[cited by applicant]
US 20050065107A1
· Hobart et al.
· 2005
[cited by applicant]
US 20050069590A1
· Buehler et al.
· 2005
[cited by applicant]
US 20050079212A1
· Wheeler et al.
· 2005
[cited by applicant]
US 20050143332A1
· Monahan et al.
· 2005
[cited by applicant]
US 20050148786A1
· Ikeda et al.
· 2005
[cited by applicant]
US 20050158302A1
· Faustman et al.
· 2005
[cited by applicant]
US 20050244961A1
· Short et al.
· 2005
[cited by applicant]
US 20050250723A1
· Hoerr et al.
· 2005
[cited by applicant]
US 20060008910A1
· Maclachlan et al.
· 2006
[cited by applicant]
US 20060069225A1
· Wintermantel et al.
· 2006
[cited by applicant]
US 20060083780A1
· Heyes et al.
· 2006
[cited by applicant]
US 20060172003A1
· Meers et al.
· 2006
[cited by applicant]
US 20060204566A1
· Smvth-Temoleton et al.
· 2006
[cited by applicant]
US 20060216343A1
· Panzner et al.
· 2006
[cited by applicant]
US 20060223939A1
· Lange et al.
· 2006
[cited by applicant]
US 20060228404A1
· Anderson et al.
· 2006
[cited by applicant]
US 20060241071A1
· Grinstaff et al.
· 2006
[cited by applicant]
US 20070135372A1
· MacLachlan et al.
· 2007
[cited by applicant]
US 20070142628A1
· Ghoshal et al.
· 2007
[cited by applicant]
US 20070172950A1
· Wheeler et al.
· 2007
[cited by applicant]
US 20070252295A1
· Panzner et al.
· 2007
[cited by applicant]
US 20070275923A1
· Chen et al.
· 2007
[cited by applicant]
US 20070281336A1
· Jendrisak et al.
· 2007
[cited by applicant]
US 20080145338A1
· Anderson et al.
· 2008
[cited by applicant]
US 20080160048A1
· Fuller
· 2008
[cited by applicant]
US 20080242626A1
· Zugates et al.
· 2008
[cited by applicant]
US 20080260706A1
· Rabinovich et al.
· 2008
[cited by applicant]
US 20090023673A1
· Manoharan et al.
· 2009
[cited by applicant]
US 20090093433A1
· Woolf et al.
· 2009
[cited by applicant]
US 20090163705A1
· Manoharan et al.
· 2009
[cited by applicant]
US 20090186805A1
· Tabor et al.
· 2009
[cited by applicant]
US 20090221684A1
· Grinstaff et al.
· 2009
[cited by applicant]
US 20090263407A1
· Dande et al.
· 2009
[cited by applicant]
US 20090270481A1
· Maclachlan et al.
· 2009
[cited by applicant]
US 20090286852A1
· Kariko et al.
· 2009
[cited by applicant]
US 20090326051A1
· Corey et al.
· 2009
[cited by applicant]
US 20100028943A1
· Thomas et al.
· 2010
[cited by applicant]
US 20100035249A1
· Hayashizaki et al.
· 2010
[cited by applicant]
US 20100036084A1
· Langer et al.
· 2010
[cited by applicant]
US 20100041152A1
· Wheeler et al.
· 2010
[cited by applicant]
US 20100047261A1
· Hoerr et al.
· 2010
[cited by applicant]
US 20100178699A1
· Gao et al.
· 2010
[cited by applicant]
US 20100189729A1
· Hoerr et al.
· 2010
[cited by applicant]
US 20100267806A1
· Bumcrot et al.
· 2010
[cited by applicant]
US 20100331234A1
· Mahon et al.
· 2010
[cited by applicant]
US 20110009641A1
· Anderson et al.
· 2011
[cited by applicant]
US 20110038941A1
· Lee et al.
· 2011
[cited by applicant]
US 20110092739A1
· Chen et al.
· 2011
[cited by applicant]
US 20110143397A1
· Kariko et al.
· 2011
[cited by applicant]
US 20110200582A1
· Baryza et al.
· 2011
[cited by applicant]
US 20110244026A1
· Guild et al.
· 2011
[cited by applicant]
US 20110256175A1
· Hope et al.
· 2011
[cited by applicant]
US 20110287435A1
· Grunenwald et al.
· 2011
[cited by applicant]
US 20110293703A1
· Mahon et al.
· 2011
[cited by applicant]
US 20110311583A1
· Manoharan et al.
· 2011
[cited by applicant]
US 20120007803A1
· Takatsuka
· 2012
[cited by applicant]
US 20120009222A1
· Nguyen et al.
· 2012
[cited by applicant]
US 20120065252A1
· Schrum et al.
· 2012
[cited by applicant]
US 20120065358A1
· Langer et al.
· 2012
[cited by applicant]
US 20120114831A1
· Semple et al.
· 2012
[cited by applicant]
US 20120128760A1
· Manoharan et al.
· 2012
[cited by applicant]
US 20120129910A1
· Thompson et al.
· 2012
[cited by applicant]
US 20120142756A1
· Guild et al.
· 2012
[cited by applicant]
US 20120195936A1
· Rudolph 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 20120251560A1
· Dahlman 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 20130017223A1
· Hope et al.
· 2013
[cited by applicant]
US 20130158021A1
· Dong et al.
· 2013
[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 20130302401A1
· Ma 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 20140094399A1
· Ianaer 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 20140161830A1
· Anderson et al.
· 2014
[cited by applicant]
US 20140162897A1
· Grunenwald 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 20140200163A1
· Mikkelsen et al.
· 2014
[cited by applicant]
US 20140200261A1
· Hoae 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
· Afevan 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 20140221248A1
· Jendrisak et al.
· 2014
[cited by applicant]
US 20140221465A1
· Bancel et al.
· 2014
[cited by applicant]
US 20140227300A1
· Chin 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
· Hoae et al.
· 2014
[cited by applicant]
US 20140275229A1
· Bancel et al.
· 2014
[cited by applicant]
US 20140288160A1
· Guild et al.
· 2014
[cited by applicant]
US 20140294937A1
· Maclachlan et al.
· 2014
[cited by applicant]
US 20140294938A1
· Guild et al.
· 2014
[cited by applicant]
US 20140294939A1
· Guild et al.
· 2014
[cited by applicant]
US 20140294940A1
· Guild et al.
· 2014
[cited by applicant]
US 20140329884A1
· Dong et al.
· 2014
[cited by applicant]
US 20140343129A1
· de Fougerolles et al.
· 2014
[cited by applicant]
US 20140363876A1
· Jendrisak et al.
· 2014
[cited by applicant]
US 20150004217A1
· Guild et al.
· 2015
[cited by applicant]
US 20150005372A1
· Hoge et al.
· 2015
[cited by applicant]
US 20150011615A1
· Manoharan et al.
· 2015
[cited by applicant]
US 20150011633A1
· Shorr et al.
· 2015
[cited by applicant]
US 20150017211A1
· de Fougerolles et al.
· 2015
[cited by applicant]
US 20150038556A1
· Heartlein et al.
· 2015
[cited by applicant]
US 20150038558A1
· Kariko 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 20150110857A1
· DeRosa et al.
· 2015
[cited by applicant]
US 20150110859A1
· Heartlein 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 20150119444A1
· Manoharan et al.
· 2015
[cited by applicant]
US 20150119445A1
· Manoharan et al.
· 2015
[cited by applicant]
US 20150157565A1
· Heartlein 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 20150191760A1
· Jendrisak et al.
· 2015
[cited by applicant]
US 20150265708A1
· 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 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 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 20170002060A1
· Bolen et al.
· 2017
[cited by applicant]
US 20170007702A1
· Heyes et al.
· 2017
[cited by applicant]
US 20190211314A1
· DeRosa et al.
· 2019
[cited by applicant]
CA 2518132A1
· 2006
[cited by applicant]
CA 2807552A1
· 2012
[cited by applicant]
CN 100569877C
· 2009
[cited by applicant]
CN 101863544A
· 2010
[cited by applicant]
DE 2520814A1
· 1976
[cited by applicant]
DE 3728917A1
· 1989
[cited by applicant]
EP 0673637A1
· 1995
[cited by applicant]
EP 0783297A1
· 1997
[cited by applicant]
EP 0853123A1
· 1998
[cited by applicant]
EP 0959092A1
· 1999
[cited by applicant]
EP 2449106A1
· 1999
[cited by applicant]
EP 1519714B1
· 2005
[cited by applicant]
EP 2045251A1
· 2009
[cited by applicant]
EP 2338478B1
· 2011
[cited by applicant]
EP 2532649A1
· 2012
[cited by applicant]
EP 2578685A2
· 2013
[cited by applicant]
EP 2823809A1
· 2015
[cited by applicant]
EP 3060258A1
· 2016
[cited by applicant]
EP 3574923A1
· 2019
[cited by applicant]
FR 2235112A1
· 1975
[cited by applicant]
GB 1072118A
· 1967
[cited by applicant]
GB 1602085A
· 1981
[cited by applicant]
JP S48022365
· 1973
[cited by applicant]
JP S49127908A
· 1974
[cited by applicant]
JP S51023537
· 1976
[cited by applicant]
JP 51125144
· 1976
[cited by applicant]
JP S63125144A
· 1988
[cited by applicant]
JP H10197978A
· 1998
[cited by applicant]
JP 11005786A
· 1999
[cited by applicant]
JP 11080142
· 1999
[cited by applicant]
JP 2001523215A
· 2001
[cited by applicant]
JP 2002167368A
· 2002
[cited by applicant]
JP 2003519199A
· 2003
[cited by applicant]
JP 4108173B2
· 2008
[cited by applicant]
JP 2008247749A
· 2008
[cited by applicant]
JP 5024216B2
· 2012
[cited by applicant]
WO WO199011092A1
· 1990
[cited by applicant]
WO WO199318229A1
· 1993
[cited by applicant]
WO WO199318754A1
· 1993
[cited by applicant]
WO WO199511004A1
· 1995
[cited by applicant]
WO WO199514651A1
· 1995
[cited by applicant]
WO WO199527478A1
· 1995
[cited by applicant]
WO WO199618372A2
· 1996
[cited by applicant]
WO WO199626179A1
· 1996
[cited by applicant]
WO WO199637211A1
· 1996
[cited by applicant]
WO WO199640964A2
· 1996
[cited by applicant]