Granted Patent
B2
US 12,552,858 · App. 17/126,833 · Granted Feb 17, 2026
Methods and compositions for delivering mRNA coded antibodies
Inventors:
Michael Heartlein (Lexington, MA); Frank DeRosa (Lexington, MA); Anusha Dias (Lexington, MA); Braydon Charles Guild (Lexington, MA)
Assignee:
TRANSLATE BIO, INC.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present invention provides, among other things, methods and compositions for delivering an antibody in vivo by administering to a subject in need thereof one or more mRNAs encoding a heavy chain and a light chain of an antibody, and wherein the antibody is expressed systemically in the subject. In some embodiments, the one or more mRNAs comprise a first mRNA encoding the heavy chain and a second mRNA encoding the light chain of the antibody.
Claims (27)
1 . A method of delivering an antibody in vivo, the method comprising:
administering to a patient in need thereof
a first mRNA encoding a heavy chain of the antibody and
a second mRNA encoding a light chain of the antibody,
wherein the first mRNA polynucleotide encoding the antibody heavy chain and the second mRNA polynucleotide encoding the antibody light chain are at a molar ratio ranging from greater than 1:1 to 10:1,
wherein the first mRNA and the second mRNA (i) each comprise a 5′ cap structure, a 3′ poly-A tail, a 5′ untranslated region and a 3′ untranslated region and (ii) are encapsulated within a liposome comprising a cationic lipid, a neutral lipid, a cholesterol-based lipid, and a PEG modified lipid,
wherein the first mRNA encoding the heavy chain and the second mRNA encoding the light chain are encapsulated within the same liposome,
wherein the composition is administered intravenously to the patient and the antibody is distributed systemically in the patient.
2 . The method of claim 1 , wherein the antibody is selected from the group consisting of anti-CCL2, anti-lysyl oxidase-like-2 (LOXL2), anti-Fit-1, anti-TNF-a, anti-Interleukin-2Ra receptor (CD25), anti-TGF, anti-B-cell activating factor, anti-alpha-4 integrin, anti-BAGE, anti-P-catenin/m, anti-Bcr-abl, anti-C5, anti-CA125, anti-CAMEL, anti-CAP-1, anti-CASP-8, anti-CD4, anti-CD19, anti-CD20, anti-CD22, anti-CD25, anti-CDC27/m, anti-CD 30, anti-CD33, anti-CD52, anti-CD56, anti-CD80, anti-CDK4/m, anti-CEA, anti-CT, anti-CTL4, anti-Cyp-B, anti-DAM, anti-EGFR, anti-ErbB3, anti-ELF2M, anti-EMMPRIN, anti-EpCam, anti-ETV6-AML 1, anti-HER2, anti-G250, anti-GAGE, anti-GnT-V, anti-Gp100, anti-HAGE, anti-HER-2/neu, anti-HLA-A*0201-R170I, anti-IGF-1R, anti-IL-2R, anti-IL-5, anti-MC1R, anti-myosin/m, anti-MUC1, anti-MUM-1, -2, -3, anti-proteinase-3, anti-p190 minor bcr-abl, anti-Pm1/RARα, anti-PRAMS, anti-PSA, anti-PSM, anti-PSMA, anti-RAGE, anti-RANKL, anti-RU1 or RU2, anti-SAGE, anti-SART-1 or anti-SART-3, anti-survivin, anti-TEL/AML1, anti-TPI/m, anti-TRP-1, anti-TRP-2, anti-TRP-2/INT2, anti-VEGF, and anti-VEGF receptor.
3 . The method of claim 1 , wherein the liposome has a size no greater than about 100 nm or 75 nm.
4 . The method of claim 1 , wherein the liposome has a size ranging from 10 nm-100 nm.
5 . The method of claim 1 , wherein the mRNAs are (i) modified to enhance stability, wherein the mRNAs are modified to include nucleoside analogs, chemically or biologically modified bases, intercalated bases, modified phosphate groups and/or modified sugars, or (ii) chemically unmodified.
6 . The method of claim 1 , wherein the mRNAs are synthesized from (i) naturally occurring nucleotides adenine (A), guanine (G), thymine (T), cytosine (C), and uracil (D), or modified nucleotide analogues selected from the group consisting of 1-methyladenine, 2-methyl-adenine, 2-methylthio-N-6-isopentenyl-adenine, N-6-isopentenyl-adenine, 2-thio-cytosine, 3-methyl-cytosine, 4-acetyl-cytosine, 5-methyl-cytosine, 2,6-diaminopurine, 1-methyl-guanine, 2-methyl-guanine, 2,2-dimethyl-guanine, 7-methylguanine, inosine, 1-methyl-inosine, pseudouracil (5-uracil), dihydro-uracil, 2-thio-uracil, 4-thiouracil, 5-carboxymethylaminomethyl-2-thio-uracil, 5-(carboxyhydroxymethyl)-uracil, 5-fluorouracil, 5-bromo-uracil, 5-carboxymethylaminomethyl-uracil, 5-methyl-2-thio-uracil, 5-methyluracil, N-uracil-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uracil, 5-methoxyaminomethyl-2-thio-uracil, 5-methoxycarbonylmethyl-uracil, 5-methoxy-uracil, uracil-5-oxyacetic acid methyl ester, uracil-5-oxyacetic acid (v), 1-methyl-pseudouracil, queosine, β-D-mannosyl-queosine, wybutoxosine, and phosphoramidates, phosphorothioates, peptide nucleotides, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine.
7 . The method of claim 1 , wherein the antibody is an IgG.
8 . The method of claim 1 , wherein the light chain is approximately 25 kD and the heavy chain is approximately 50-70 kD.
9 . A pharmaceutical composition for systemic distribution of an antibody in vivo comprising a first mRNA encoding a heavy chain of the antibody and a second mRNA encoding a light chain of the antibody,
wherein the first mRNA polynucleotide encoding the antibody heavy chain and the second mRNA polynucleotide encoding the antibody light chain are at a molar ratio ranging from greater than 1:1 to 10:1,
wherein the first mRNA and the second mRNA (i) each comprise a 5′ cap structure, a 3′ poly-A tail, a 5′ untranslated region and a 3′ untranslated region and (ii) are encapsulated within a liposome comprising a cationic lipid, a neutral lipid, a cholesterol-based lipid, and a PEG-modified lipid,
wherein the first mRNA encoding the heavy chain and the second mRNA encoding the light chain are encapsulated within the same liposome, and
wherein the composition is formulated for intravenous (IV) delivery.
10 . The composition of claim 9 , wherein the liposome has a size no greater than about 100 nm or 75 nm.
11 . The composition of claim 9 , wherein the liposome has a size ranging from 10 nm-100 nm.
12 . The composition of claim 9 , wherein the mRNAs are (i) modified to enhance stability, wherein the mRNAs are modified to include nucleoside analogs, chemically or biologically modified bases, intercalated bases, modified phosphate groups and/or modified sugars, or (ii) chemically unmodified.
13 . The composition of claim 9 , wherein the mRNAs are synthesized from (i) naturally occurring nucleotides adenine (A), guanine (G), thymine (T), cytosine (C), and uracil (D), or modified nucleotide analogues selected from the group consisting of 1-methyladenine, 2-methyl-adenine, 2-methylthio-N-6-isopentenyl-adenine, N-6-methyl-adenine, N-6-isopentenyl-adenine, 2-thio-cytosine, 3-methyl-cytosine, 4-acetyl-cytosine, 5-methyl-cytosine, 2,6-diaminopurine, 1-methyl-guanine, 2-methyl-guanine, 2,2-dimethyl-guanine, 7-methylguanine, inosine, 1-methyl-inosine, pseudouracil (5-uracil), dihydro-uracil, 2-thio-uracil, 4-thiouracil, 5-carboxymethylaminomethyl-2-thio-uracil, 5-(carboxyhydroxymethyl)-uracil, 5-fluorouracil, 5-bromo-uracil, 5-carboxymethylaminomethyl-uracil, 5-methyl-2-thio-uracil, 5-methyluracil, N-uracil-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uracil, 5-methoxyaminomethyl-2-thio-uracil, 5-methoxycarbonylmethyl-uracil, 5-methoxy-uracil, uracil-5-oxyacetic acid methyl ester, uracil-5-oxyacetic acid (v), 1-methyl-pseudouracil, queosine, β-D-mannosyl-queosine, wybutoxosine, and phosphoramidates, phosphorothioates, peptide nucleotides, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine.
14 . The composition of claim 9 , wherein the antibody is an IgG.
15 . The composition of claim 9 , wherein the antibody is selected from the group consisting of anti-CCL2, anti-lysyl oxidase-like-2 (LOXL2), anti-Flt-1, anti-TNF-α, anti-Interleukin-2Rα receptor (CD25), anti-TGFp, anti-B-cell activating factor, anti-alpha-4 integrin, anti-BAGE, anti-β-catenin/m, anti-Bcr-abl, anti-C5, anti-CA125, anti-CAMEL, anti-CAP-1, anti-CASP-8, anti-CD4, anti-CD19, anti-CD20, anti-CD22, anti-CD25, anti-CDC27/m, anti-CD 30, anti-CD33, anti-CD52, anti-CD56, anti-CD80, anti-CDK4/m, anti-CEA, anti-CT, anti-CTL4, anti-Cyp-B, anti-DAM, anti-EGFR, anti-ErbB3, anti-ELF2M, anti-EMMPRIN, anti-EpCam, anti-ETV6-AML1, anti-HER2, anti-G250, anti-GAGE, anti-GnT-V, anti-Gp100, anti-HAGE, anti-HER-2/neu, anti-HLA-A*0201-R170I, anti-IGF-1R, anti-IL-2R, anti-IL-5, anti-MC1R, anti-myosin/m, anti-MUC1, anti-MUM-1, -2, -3, anti-proteinase-3, anti-p190 minor bcr-abl, anti-Pm1/RARα, anti-PRAMS, anti-PSA, anti-PSM, anti-PSMA, anti-RAGE, anti-RANKL, anti-RU1 or RU2, anti-SAGE, anti-SART-1 or anti-SART-3, anti-survivin, anti-TEL/AML1, anti-TPI/m, anti-TRP-1, anti-TRP-2, anti-TRP-2/INT2, anti-VEGF, and anti-VEGF receptor.
16 . The composition of claim 9 , wherein the light chain is approximately 25 kD and the heavy chain is approximately 50-70 kD.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 30, 2020
From: HEARTLEIN, MICHAEL; DEROSA, FRANK; GUILD, BRAYDON CHARLES; DIAS, ANUSHA
To: SHIRE HUMAN GENETIC THERAPIES, INC.
Reel/Frame 054774/0464 →
CHANGE OF NAME
Recorded Dec 30, 2020
From: RANA THEREAPEUTICS, INC.
To: TRANSLATE BIO, INC.
Reel/Frame 054870/0596 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 30, 2020
From: SHIRE HUMAN GENETIC THERAPIES, INC.
To: RANA THERAPEUTICS, INC.
Reel/Frame 054870/0600 →
Continuity (6)
Continuation
14775835
Provisional Application
61920165
· Dec 23, 2013
Provisional Application
61784903
· Mar 14, 2013
References Cited (400)
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
· Hoae 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 Fouaerolles 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
· Fouaerolles 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 Fouaerolles 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 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 20070265220A1
· Rossi et al.
· 2007
[cited by applicant]
US 20080145413A1
· Panzner et al.
· 2008
[cited by applicant]
US 20090270481A1
· Maclachlan et al.
· 2009
[cited by applicant]
US 20100041152A1
· Wheeler et al.
· 2010
[cited by applicant]
US 20100189729A1
· Hoerr et al.
· 2010
[cited by applicant]
US 20110244026A1
· Guild et al.
· 2011
[cited by applicant]
US 20110256175A1
· Hooe 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 Fouaerolles 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 Fouaerolles 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
· Hoqe 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 Fouaerolles et al.
· 2014
[cited by applicant]
US 20150005372A1
· Hoqe et al.
· 2015
[cited by applicant]
US 20150017211A1
· de Fouaerolles 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
· Hoae et al.
· 2016
[cited by applicant]
US 20160151284A1
· Heves et al.
· 2016
[cited by applicant]
US 20160158385A1
· Bancel et al.
· 2016
[cited by applicant]
US 20160193299A1
· de Fouaerolles et al.
· 2016
[cited by applicant]
US 20160194368A1
· Hooe et al.
· 2016
[cited by applicant]
US 20160194625A1
· Hoae 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 Fouaerolles 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
· Hoae 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-Mileczek 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 20180161451A1
· Fotin-Mileczek et al.
· 2018
[cited by applicant]
CA 2807552
· 2012
[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 WO0246430A2
· 2002
[cited by applicant]
WO WO2003048306A2
· 2003
[cited by applicant]
WO WO2005026372
· 2005
[cited by applicant]
WO WO2005121348
· 2005
[cited by applicant]
WO WO2006017325A2
· 2006
[cited by applicant]
WO WO2008083949
· 2008
[cited by applicant]
WO WO2009086558A1
· 2009
[cited by applicant]
WO WO2009127060
· 2009
[cited by applicant]
WO WO2010042877
· 2010
[cited by applicant]
WO WO2010054406A1
· 2010
[cited by applicant]
WO WO2011068810
· 2011
[cited by applicant]
WO WO2011141705
· 2011
[cited by applicant]
WO WO2012006377A2
· 2012
[cited by applicant]
WO WO2012006378A1
· 2012
[cited by applicant]
WO WO2012019168
· 2012
[cited by applicant]
WO WO2012045082A2
· 2012
[cited by applicant]
WO WO2012135805
· 2012
[cited by applicant]
WO WO2012170889A1
· 2012
[cited by applicant]
WO WO2012170930
· 2012
[cited by applicant]
WO WO2013039857
· 2013
[cited by applicant]
WO WO2013039861
· 2013
[cited by applicant]
WO WO2013090186
· 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 WO2013185069A1
· 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 WO2014152774A1
· 2014
[cited by applicant]
WO WO2014158795
· 2014
[cited by applicant]
WO WO2014159813
· 2014
[cited by applicant]
WO WO2015048744
· 2015
[cited by applicant]
WO WO2015051169
· 2015
[cited by applicant]
WO WO2015051173
· 2015
[cited by applicant]
WO WO2015058069
· 2015
[cited by applicant]
WO WO2015061461A1
· 2015
[cited by applicant]
WO WO2015085318
· 2015
[cited by applicant]
WO WO2015089511
· 2015
[cited by applicant]
WO WO2015011633
· 2016
[cited by applicant]
WO WO2016054421
· 2016
[cited by applicant]
WO WO2016071857
· 2016
[cited by applicant]
WO WO2016077123
· 2016
[cited by applicant]
WO WO2016077125
· 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 WO2012170930A1
· 2021
[cited by applicant]
Whitehead, K. et al., Nature Comm., 2014, vol. 5: 22 pages.
[cited by examiner]
Cheng, X. et al., Adv. Drug Delivery Rev., 2016, vol. 99: pp. 129-137.
[cited by examiner]
Tenchov, R. et al., ACS Nano, 2021, vol. 15: pp. 16982-17015.
[cited by examiner]
Thran, M. et al., EMBO Mol. Med., 2017, vol. 9: pp. 1434-1447.
[cited by examiner]
Kariko et al., “Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability”, Molecular Therapy, vol. 16, No. 11, Nov. 2008, pp. 1833-184…
[cited by applicant]
Xingfang et al., “In Vitro and in Vivo mRNA Delivery Using Lipid-Enveloped pH-Responsive Polymer Nanoparticles”, Molecular Pharmaceutics, vol. 8, No. 3, Jun. 6, 2011, pp. 774-787, DOI: 10.1021/mp100390w.
[cited by applicant]
Felgner et al., “Lipofection: A highly efficient, lipd-mediated DNA-trasnfection procedure”, PNAS, vol. 84:
[cited by applicant]
Geall et al., “Nonviral delivery of self-amplifying RNA vaccines”, Proc Natl Acad Sci USA, 109(36):14604-9 (2012).
[cited by applicant]
Gilkeson et al.,“ Induction of Cross-Reactive Anti-dsDNA Antibodies in Preautoimmune NZB/NZW Mice by Immunization with Bacterial Dna” J. Clin. Invest., vol. 95, No. 3, pp. 1398-1402 (1995).
[cited by applicant]
Hara et al., “Some properties of IgG against diphtheria toxin synthesized in Xenopus oocytes containing mRNA from hybridoma”, Biochimica et Biophysica Acta, vol. 85, p. 188-198 (1985).
[cited by applicant]
Ho et al., “IRES-mediated Tricistronic vectors for enhancing generation of high monoclonal antibody expressina CHO cellines”, J. Biotech., vol. 157: pp. 130-139. (2011).
[cited by applicant]
Kober et al., “Optimized signal peptides for the development of high expressing CHO cell lines”, Biotechnol Bioena., vol. 110, rm.1164-1173 (2013).
[cited by applicant]
Love et al., “Lipid-like materials for low-dose, in vivo gene silencing”, PNAS, 107(5): 1864-1869 (2010).
[cited by applicant]
Maclachlan et al., “Liposomal Formulations for Nucleic Acid Delivery”, CH 9 in Antisense Drug Technology; Principles, Strategies, and Applications 2
[cited by applicant]
Martinon et al., Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA, Eur J Immunol. 23(7):1719-22 (1993).
[cited by applicant]
Monteith et al., “Immune stimulation—a class effect of phosphorothioate oligodeoxynucleotides in rodents” Anticancer Drug Design, vol. 12, No. 5, pp. 421-432 (1997).
[cited by applicant]
Nakanishi et al., “New Transfection Agents Based on Liposomes Containing Biosurfactant MEL-A”, Pharmaceuticals, 5(3): 411- 420 (2013).
[cited by applicant]
Philippot et al., “A very mild method allowing the encapsulation of very high amounts of macromolecules into very large (1000 nm) unilamellar liposomes”, Biochimica et Biophysica Acta, 734(2): 137-143 (1983).
[cited by applicant]
Pisani et al., “Neutral Liposomes and DNA Transfection”, CH 14 in Non-Viral Gene Therapy edited by Xubu Yuan, Paaes 319-344 (2011).
[cited by applicant]
Ramezani et al., “Improving Pertuzumab production by gene optimization and proper signal peptide selection”, Protein Exp. Purif., vol. 135: DD. 24-32 (2017).
[cited by applicant]
Robinson et al., “Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis”, Molecular Therapy 26(8): 1-13 (2018).
[cited by applicant]
Schlatter et al., “On the Optimal Ratio of Heavy to Light Chain Genes for Efficient Recombinant Antibody Production by CHO Cells”, Biotechnol. Prag. vol. 21: pp. 122-133 (2005).
[cited by applicant]
Su, X., et al., “In Vitro and in Vivo mRNA Delivery Using Lipid-Enveloped pH-Responsive Polymer Nanoparticles”, Molecular Pharmaceutics, vol. 8, No. 3, 774-787 (2011).
[cited by applicant]
Tavernier, G., et al., “mRNA as gene therapeutic: How to control protein expression”, Journal of Controlled Release, vol. 150, No. 3, Daaes 238-247 (2011).
[cited by applicant]
Thran et al., “mRNA mediates passive vaccination against infectious agents, toxins, and tumors”, EMBO Molecular Medicine, vol. 9(10): DD 1434-1447 (Aug. 9, 2017).
[cited by applicant]
Vazquez-Lombardi et al., “Transient expression of human antibodies in mammalian cells”, Nature Protocols, vol. 13, No. 1, DD 99-117 (2018).
[cited by applicant]
Summons to Attend Oral Proceedings for European Patent Application No. 14717945.1, dated Jul. 4, 2024.
[cited by applicant]
Notice of Opposition by Opponent 1 Glaxosmithkline Biologicals SA, regarding European Patent No. 2970456 (Patent Application No. 14717945.1), dated Feb. 18, 2022. (Opposition 1).
[cited by applicant]
Notice of Opposition by Opponent 2 Withers & Rogers LLP, regarding European Patent No. 2970456 (Patent Application No. 14717945.1), dated Feb. 18, 2022. (Opposition 2).
[cited by applicant]
Notice of Opposition by Opponent 3 Strawman Limited, regarding European Patent No. 2970456 (Patent Application No. 14717945.1), dated Feb. 18, 2022. (Opposition 3).
[cited by applicant]
Notice of Opposition by Opponent 4 EIP Limited, regarding European Patent No. 2970456 (Patent Application No. 14717945.1), dated Feb. 18, 2022. (Opposition 4).
[cited by applicant]
D9—Tjelle et al., Monoclonal antibodies produced by muscle after plasmid injection and electroporation, Mol. Ther., Mar. 2004, 9(3): 328-336.
[cited by applicant]
D10—Strohl et al., Therapeutic Antibody Engineering: Current and Future Advances Driving the Strongest Growth Area in the Pharmaceutical Industry, Oct. 16, 2012, pp. 197-199.
[cited by applicant]
D11—Jefferis et al., Isotype and glycoform selection for antibody therapeutics, Arch. Biochem. Biophys., Oct. 15, 2012, 526(2): 159-166.
[cited by applicant]
D12—Xu et al., Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid-based therapeutics, J. Pharm. Sci., Jan. 2011, 100(1): 38-52.
[cited by applicant]
D14—Lobo et al. Antibody pharmacokinetics and pharmacodynamics, J. Pharm. Sci., Nov. 2004, 93(11): 2645-2668.
[cited by applicant]
D15—Geall et al., Nonviral delivery of self-amplifying RNA vaccines, PNAS, Aug. 20, 2012, 109(36): 14604-14609.
[cited by applicant]
D16—Textbook, Machlachlan, 2007, Antisense Drug Technologies (edited by Stanley Crooke; Chapter 9, pp. 237-270.
[cited by applicant]
D17—Textbook Pisani et al., Nov. 2011, Non-viral Gene Therapy, Chapter 14, pp. 319-344.
[cited by applicant]
D18—Pascolo, Messenger RNA-based vaccines, Expert Opin. Biol. Ther., Aug. 2004, 4(8):1285-1294.
[cited by applicant]
D19—Pascolo, Vaccination with messenger RNA, Methods Mol. Med., 2006; 127: 23-40.
[cited by applicant]
D20—Pascolo, Vaccination with messenger RNA (mRNA), Handbook of Exp. Pharmacology 183, 2008, 183: 221-235.
[cited by applicant]
D23—Janeway, Immunobiology: The immune system in health and disease, 5th edition, Garland Science, 2001.
[cited by applicant]
D24—Wang et al., Systemic delivery of modified mRNA encoding herpes simplex virus 1 thymidine kinase for targeted cancer gene therapy, Mol. Ther., Feb. 2013 21(2): 358-367, Epub Dec. 11, 2012.
[cited by applicant]
D27—Tzaban et al., The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity, J. Cell Biol., May 18, 2009, 185(4): 6 73-684.
[cited by applicant]
D29—Invitrogen fact sheet on RNAiMax (2013).
[cited by applicant]
D30—Invitrogen fact sheet on RNAiMax (2013)—Annex 1 / Calculations.
[cited by applicant]
D31—Pascolo, Plasmid DNA and Messenger RNA for Therapy, pp. 971-1012, Epub Mar. 15, 2010.
[cited by applicant]
D32—Van Hoecke et al., How mRNA therapeutics are entering the monoclonal antibody field, J. Transl. Med., Feb. 22, 2019, 17(1): 54.
[cited by applicant]
D33—Lin et al., Preclinical Pharmacokinetics, Interspecies Scaling, and Tissue Distribution of a Humanized Monoclonal Antibody against Vascular Endothelial Growth Factor, J. Pharma. Experi. Ther., Jan. 1, 1999, 288(1): …
[cited by applicant]
D34—Mori et al., Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model, Blood Cancer J., Apr. 20, 2012, 2: e67.
[cited by applicant]
D35—Han et al., Population pharmacokinetics of bevacizumab in cancer patients with external validation, Cancer Chemother. Pharmacol., Jun. 21, 2016, 78: 341-351.
[cited by applicant]
D36—Hillmen et al., The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria, N. Engl. J. Med., Sep. 21, 2006, 355(12): 1233-1243.
[cited by applicant]
D37—Bakker et al., Therapeutic Antibody Gene Transfer: An Active Approach to Passive Immunity, Mol. Ther., Sep. 2004, 10(3): 411-416.
[cited by applicant]
D38—Fang et al., Stable antibody expression at therapeutic levels using the 2A peptide, Nat. Biotechnol., May 2005, 23(5): 584-590.
[cited by applicant]
D39—Pardi et al., Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge, Nature Communications, Mar. 2, 2017, 8: 14630.
[cited by applicant]
D40—Schlake et al., mRNA: A Novel Avenue to Antibody Therapy?, Mol. Ther., Apr. 10, 2019, 27(4): 773-784.
[cited by applicant]
D41—Probst et al., Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent, Gene Ther., Aug. 2007, 14(15): 1175-1180.
[cited by applicant]
D44—Yang et al., Mutated polyadenylation signals for controlling expression levels of multiple genes in mammalian cells, Biotechnol. Bioeng., Mar. 1, 2009, 102(4): 1152-1160.
[cited by applicant]
D45—Lee et al., A clone screening method using mRNA levels to determine specific productivity and product quality for monoclonal antibodies, Biotechnol. Bioeng., Mar. 1, 2009, 102(4): 1107-1118.
[cited by applicant]
D46—Dorai et al., Correlation of heavy and light chain mRNA copy numbers to antibody productivity in mouse myeloma production cell lines, Hybridoma (Larchmt), Feb. 2006, 25(1): 1-9.
[cited by applicant]
D48—Sandhu et al., A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors, Cancer Chemother. Pharmacol., Apr. 2013…
[cited by applicant]
D49—Duvvuri et al., Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma, Clin. Cancer Res., Oct. 1, 2019, 25(19): 5752-5758.
[cited by applicant]
D50 - JAYARAMAN et al., Jul. 10, 2012, Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo, Chemie International Edition, 109(36): 8529-8533.
[cited by applicant]
D51—Akinc et al., The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs, Nature Nanotechnology, Dec. 2019, 14(12): 1084-1087.
[cited by applicant]
D52—Kulkarni et al., Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility, Nucleic Acid Therapeutics, Jun. 1, 2018, 28(3): 146-157.
[cited by applicant]
D53—Schlich et al., Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles, Bioeng. & Transl. Med., Mar. 20, 2021, 6(2): e10213.
[cited by applicant]
D55—Jiang et al., Gene therapy using adenovirus-mediated full-length anti-HER-2 antibody for HER-2 overexpression cancers, Clin. Cancer Res., Oct. 15, 2006, 12(20 Pt. 1): 6179-6185.
[cited by applicant]
D57—Semple et al., Feb. 9, 2001, Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures, Biochimica et Biophysica A…
[cited by applicant]
D58—Carrasco et al., Aug. 11, 2021, Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration, Communications Biology, 4(1): 956.
[cited by applicant]
D60—Schlatter et al., Jan.-Feb. 2005, On the optimal ratio of heavy to light chain genes for efficient recombinant antibody production by CHO cells, Biotechnol Prog, 21(1): 122-133.
[cited by applicant]
D61—Schlake et al., Oct. 12, 2012, Developing mRNA-vaccine technologies, RNA Biology, 9(11): 1319-1330.
[cited by applicant]
D62—Schlake et al., Oct. 17, 2018, mRNA as novel technology for passive immunotherapy, Cellular and Molecular Life Sciences, 76(2): 301-328.
[cited by applicant]
D63—Lee et al., Jul. 1, 1999, BiP and Immunoglobulin Light Chain Cooperate to Control the Folding of Heavy Chain and Ensure the Fidelity of Immunoglobulin Assembly, Molecular Biology of the Cell, 10(7): 2209-2219.
[cited by applicant]
D64—Golay et al., Aug. 8, 2013, Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics, MAbs, 5(6): 826-837.
[cited by applicant]
D65—Lutterbueseet al., Apr. 15, 2007, Selective targeting and potent control of tumor growth using an EphA2/CD3-bispecific single-chain antibody construct, Cancer Immunol Immunotherapy, 56(4): 3927-3935.
[cited by applicant]
D66—Rybakova et al., Aug. 7, 2019, mRNA Delivery for Therapeutic Anti-HER2 Antibody Expression In Vivo, Molecular Therapy, 27(8): 1415-1423.
[cited by applicant]
D67—Thran et al., Aug. 9, 2017, mRNA mediates passive vaccination against infectious agents, toxins, and tumors, EMBO Molecular Medicine, 9: 1434-1447.
[cited by applicant]
D68—Razpotnik et al., Sep. 25, 2017, Targeting Malignant Brain Tumors with Antibodies, Frontiers in Immunology. 8: 1181.
[cited by applicant]
D69—Pardi et al., 2015, Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes, Journal of Controlled Release, Nov. 10, 2015, 217: 345-351.
[cited by applicant]
D70—Sonneveld et al., Aug. 2020, Heterogeneity in mRNA Translation, Trends in Cell Biology, 30(8): 606-618.
[cited by applicant]
D71—Tiwari et al., Oct. 1, 2018, Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection, Nature Communications, 9: 3999.
[cited by applicant]
D72—Stadler et al., Jul. 2017, Elimination of large tumors in mice by mRNA-encoded bispecific antibodies, Nature Medicine, 23(7): 815-817.
[cited by applicant]
D73—Kowalski et al., Apr. 10, 2019, Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery, Molecular Therapy, 27(4): 710-728.
[cited by applicant]
D74—Thess et al., Sep. 2015, Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals, Mol. Ther., 23(9): 1459-1464.
[cited by applicant]
D75—Sabnis et al., Jun. 6, 2018, A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non- human Primates, The American Society of Gene and Cell Therapy, Molec…
[cited by applicant]
D76—Thermofisher Scientific website extract: https://www.thermofisher.com/uk/en/home/references/gibco-cell-culture-basics/transfection-basics/gene-delivery-technologies/cationic-lipid-mediated-delivery/how-cationic-lipi…
[cited by applicant]
D79—Carter May 2006, Potent antibody therapeutics by design, Nature Reviews Immunology, 6(5): 343-357.
[cited by applicant]
D80—Chen et al., Oct. 15, 1997, Humanization of an Anti-Vascular Endothelial Growth Factor Monoclonal Antibody for the Therapy of Solid Tumors and Other Disorders, Cancer Research, 57(20): 4593-4599.
[cited by applicant]
D81—In-Vivo Science Inc. website extract NOG mouse: https://www.invivoscience.com/en/nog_mouse.html.
[cited by applicant]
D82—Ruschitzka et al., Oct. 10, 2000, Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin, PNAS, 97(21): 11609-11613.
[cited by applicant]
D83—Hitomi et al., Sep. 27, 2017, Science Translational Medicine, Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice, 9(409): eaaj2300.
[cited by applicant]
D83a—Supplementary materials for HITOMI et al., Sep. 27, 2017, Science Translational Medicine, Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice, 9(409): eaaj2300.
[cited by applicant]
D84—Tavernier et al., Mar. 30, 2011, mRNA as gene therapeutic: How to control protein expression, Journal of Controlled Release, 150(3): 238-247.
[cited by applicant]
D85—Kose et al., May 14, 2019, A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection, Sci Immunol., 4(35): 1-11.
[cited by applicant]
D86—Mucker et al., May 10, 2022, Lipid nanoparticle delivery of unmodified mRNAs encoding multiple monoclonal antibodies targeting poxviruses in rabbits, Mol. Ther. Nucleic Acids, 28: 847-858.
[cited by applicant]
U.S. Appl. No. 14/775,835 2016/0031981 U.S. Pat. No. 10,087,247, filed Mar. 14, 2014 Feb. 4, 2016 Oct. 2, 2018, Michael Heartlein, Methods and Compositions for Delivering mRNA Coded Antibodies.
[cited by applicant]
U.S. Appl. No. 16/129,412 2019/0071495 U.S. Pat. No. 10,584,165, filed Sep. 12, 2018 Mar. 7, 2019 Mar. 10 2020, Michael Heartlein, Methods and Compositions for Delivering mRNA Coded Antibodies.
[cited by applicant]
16/752,3273 2020/0157205 U.S. Pat. No. 10,899,830, Jan. 24, 2020 May 21, 2020 Jan. 26, 2021, Michael Heartlein, Methods and Compositions for Delivering mRNA Coded Antibodies.
[cited by applicant]
U.S. Appl. No. 17/126,833 2021/0206846, filed Dec. 18, 2020 Jul. 8, 2021, Michael Heartlein, Methods and Compositions for Delivering mRNA Coded Antibodies.
[cited by applicant]
Reply of the Patent Proprietor to the Notice(s) of Opposition—Response to the Opposition Division's preliminary opinion of Jul. 4, 2024, Submission in Opposition Proceedings for EP 2970456 (Patent Application No. 147179…
[cited by applicant]
D89—Hu et al., Functions and Clinical Relevance of Liver-Derived Immunoglobulins, Adv Exp Med Biol, 2024, 1445: 91-99.
[cited by applicant]
D90—Wu et al., Antibody-secreting cell responses in the mouse liver, Immunology, Nov. 1992, 77(3): 443-448.
[cited by applicant]
D91—Ballow et al., Primary immunodeficiency disorders: Antibody deficiency, Journal of Allergy and Clinical Immunology, Apr. 2002, 109(4): 581-591.
[cited by applicant]
D92—Healy et al., Biology of the Endoplasmic Reticulum, Endoplasmic Reticulum Stress in Health and Disease, Jan. 1, 2012, pp. 3-22.
[cited by applicant]
D93—Moore et al., The Unfolded Protein Response in Secretory Cell Function, Annual Review of Genetics, Dec. 2012, 46: 165-183, First published Aug. 28, 2012.
[cited by applicant]
D94—Gass et al., The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells, Molecular Immunology, Feb. 2008, 45(4): 1035-1043, Epublished Sep. 5, 2007.
[cited by applicant]
D95—Ji et al., ER stress: Can the liver cope?, Journal of Hepatology, Aug. 2006, 45(2): 321-333.
[cited by applicant]
D96—Nishimiya Proteins improving recombinant antibody production in mammalian cells, Applied Microbiology and Biotechnology, 2014, 98: 1031-1042.
[cited by applicant]
D97—Kirk et al., Biogenesis of secretory organelles during B cell differentiation, Journal of Leukocyte Biology, Feb. 2010, 87(2): 245-255, Epublished Nov. 4, 2009.
[cited by applicant]
D98—Ollila et al., Cells in focus - B cells, The International Journal of Biochemistry & Cell Biology, Mar. 2005, 37(3): 518-523.
[cited by applicant]
Opposition to EP 2970456 (Patent Application No. 14717945.1), 04 Written Submissions Under Rule 116 EPC filed on Jul. 23, 2025, filed by Opponent 4 EIP. (
[cited by applicant]
D99—Vermiere et al., Value of drug level testing and antibody assays in optimising biological therapy, Frontline Gastroenterol., Jan. 2013, 4(1) :41-43, Epub Sep. 5, 2012, doi: 10.1136/flgastro-2012-100241.
[cited by applicant]
D100—Yang et al., A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer, N Engl J Med., Jul. 31, 2003, 349(5): 427-434, doi: 10.1056/NEJMoa021491.
[cited by applicant]
D101—Gordon et al., Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer, J Clin Oncol., Feb. 1, 2001, 19(3): 843-850, doi: 10.1200/JCO.2…
[cited by applicant]
D102—Papachristos et al., Correlation Between Bevacizumab Exposure and Survival in Patients with Metastatic Colorectal Cancer, Oncologist, Oct. 2020, 25(10): 853-858, Epub Apr. 28, 2020, doi: 10.1634/theoncologist.2019-…
[cited by applicant]
D103—Akagi et al., Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer, Lung Cancer, Apr. 2023, 178: 247-253, Epub Mar. …
[cited by applicant]
D104—Koguchi et al., Trough levels of ipilimumab in serum as a potential biomarker of clinical outcomes for patients with advanced melanoma after treatment with ipilimumab, J Immunother Cancer, Oct. 2021, 9(10): e002663…
[cited by applicant]
D105—Woyach et al., A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL, Blood, Dec. 4, 2014, 124(24): 3553-3560, Epub Oct. 9, 2014, doi: 1…
[cited by applicant]
D106—Hillmen et al., Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria, N Engl J Med., Feb. 5, 2004, 350(6): 552-559, doi: 10.1056/NEJMoa031688.
[cited by applicant]
D107—Ishida et al., Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes, J Control Release, May 1, 2006, 112(1): 15-25, E…
[cited by applicant]
D108—Yang et al., Recent Advances in Lipid Nanoparticles for Delivery of mRNA, Pharmaceutics, Dec. 1, 2022, 14(12): 2682, doi: 10.3390/pharmaceutics14122682.
[cited by applicant]