Granted Patent
B2
US 12,331,077 · App. 17/293,364 · Granted Jun 17, 2025
Stabilized pre-fusion RSV F proteins
Assignee:
Janssen Vaccines & Prevention B.V.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Provided are stable pre-fusion respiratory syncytial virus (RSV) F proteins. Also provided are immunogenic compositions comprising RSV F proteins and uses thereof for the prevention and/or treatment of RSV infection. Also provided are nucleic acids encoding the stable pre-fusion RSV F proteins.
Claims (19)
1. A recombinant pre-fusion respiratory syncytial virus (RSV) Fusion (F) protein comprising stabilizing amino acid mutations on positions 101, 152, and 486, wherein the amino acid on position 101 is Q, the amino acid on position 152 is M, and the amino acid on position 486 is N, and wherein the stabilizing amino acid mutations on the indicated positions increase the stability of the protein in the pre-fusion conformation, and wherein the amino acid positions of the F protein are to be numbered with reference to the numbering of the F protein of SEQ ID NO: 13 (for subgroup A) or SEQ ID NO: 14 (for subgroup B).
2. The recombinant pre-fusion RSV F protein of claim 1 , wherein the recombinant pre-fusion RSV F protein comprises at least one additional stabilizing amino acid mutation present on position 79, 226, and/or 354, and wherein the stabilizing amino acid mutation on position 79 is a mutation of the amino acid isoleucine (I) into methionine (M), the stabilizing amino acid mutation on position 354 is a mutation of the amino acid glutamine (Q) into leucine (L), and the stabilizing amino acid mutation on position 226 is a mutation of the amino acid lysine (K) into methionine (M).
3. The recombinant pre-fusion RSV F protein of claim 2 , wherein the recombinant pre-fusion F protein comprises four, five, six, or more of the stabilizing amino acid mutations.
4. The recombinant pre-fusion RSV F protein of claim 1 , wherein the protein is recognized by a pre-fusion specific monoclonal antibody, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 16 and a light chain comprising the amino acid sequence of SEQ ID NO: 17 and/or a pre-fusion specific monoclonal antibody, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 18 and a light chain comprising the amino acid sequence of SEQ ID NO: 19.
5. The recombinant pre-fusion RSV F protein of claim 1 , wherein the protein is trimeric.
6. The recombinant pre-fusion RSV F protein of claim 1 , comprising a truncated F1 domain and a heterologous trimerization domain linked to said truncated F1 domain.
7. The recombinant pre-fusion RSV F protein according to claim 6 , wherein the heterologous trimerization domain comprises the amino acid sequence
(SEQ ID NO: 15)
GYIPEAPRDGQAYVRKDGEWVLLSTFL.
8. The recombinant pre-fusion RSV F protein according to claim 6 , wherein the trimerization domain is linked to amino acid residue 513 of the RSV F protein.
9. A nucleic acid molecule encoding the recombinant pre-fusion RSV F protein according to claim 1 .
10. The nucleic acid molecule according to claim 9 , wherein the nucleic acid molecule has been codon-optimized for expression in mammalian cells.
11. A vector comprising the nucleic acid molecule according to claim 9 .
12. A composition comprising the recombinant pre-fusion RSV F protein according to claim 1 and a pharmaceutically acceptable carrier.
13. A method of inducing an immune response against RSV F protein in a subject, comprising administering to the subject the composition according to claim 12 .
14. A method of vaccinating a subject against RSV comprising administering to the subject the composition according to claim 12 .
15. A method of preventing and/or treating an RSV infection in a subject in need thereof, comprising administering to the subject the composition according to claim 12 .
16. A method of inducing an immune response against respiratory syncytial virus (RSV) Fusion (F) protein in a subject, comprising administering to the subject a recombinant pre-fusion RSV F protein comprising stabilizing amino acid mutations in positions 101, 152, and 486, wherein the amino acid on position 101 is Q, the amino acid on position 152 is M, and the amino acid on position 486 is N, and wherein the stabilizing amino acid mutations on the indicated positions increase the stability of the protein in the pre-fusion conformation, and wherein the amino acid positions of the F protein are to be numbered with reference to the numbering of the F protein of SEQ ID NO: 13 (for subgroup A) or SEQ ID NO: 14 (for subgroup B).
17. A method of preventing and/or treating a respiratory syncytial virus (RSV) infection in a subject in need thereof, comprising administering to the subject a recombinant pre-fusion RSV F protein comprising stabilizing amino acid mutations in positions 101, 152, and 486, wherein the amino acid on position 101 is Q, the amino acid on position 152 is M, and the amino acid on position 486 is N, and wherein the stabilizing amino acid mutations on the indicated positions increase the stability of the protein in the pre-fusion conformation, and wherein the amino acid positions of the F protein are to be numbered with reference to the numbering of the F protein of SEQ ID NO: 13 (for subgroup A) or SEQ ID NO: 14 (for subgroup B).
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 15, 2021
From: LANGEDIJK, JOHANNES PETRUS MARIA
To: JANSSEN VACCINES & PREVENTION B.V.
Reel/Frame 057806/0916 →
Priority Claims (1)
EP 18205863
· Nov 13, 2018
· regional
Continuity (1)
References Cited (280)
US 4235877A
· Fullerton
· 1980
[cited by applicant]
US 4372945A
· Likhite
· 1983
[cited by applicant]
US 4474757A
· Arnon et al.
· 1984
[cited by applicant]
US 5057540A
· Kensil et al.
· 1991
[cited by applicant]
US 5122458A
· Post et al.
· 1992
[cited by applicant]
US 5385839A
· Stinski
· 1995
[cited by applicant]
US 5559099A
· Wickham
· 1996
[cited by applicant]
US 5837511A
· Falck-Pedersen
· 1998
[cited by applicant]
US 5837520A
· Shabram
· 1998
[cited by applicant]
US 5846782A
· Wickham
· 1998
[cited by applicant]
US 5851806A
· Kovesdi
· 1998
[cited by applicant]
US 5851808A
· Elledge
· 1998
[cited by applicant]
US 5891690A
· Massie
· 1999
[cited by applicant]
US 5965541A
· Wickham
· 1999
[cited by applicant]
US 5981225A
· Kochanek
· 1999
[cited by applicant]
US 5994106A
· Kovesdi
· 1999
[cited by applicant]
US 5994108A
· Gaynor
· 1999
[cited by applicant]
US 5994128A
· Fallaux
· 1999
[cited by applicant]
US 6020191A
· Scaria
· 2000
[cited by applicant]
US 6040174A
· Imler
· 2000
[cited by applicant]
US 6083716A
· Wilson
· 2000
[cited by applicant]
US 6113913A
· Brough
· 2000
[cited by applicant]
US 6225289B1
· Kovesdi
· 2001
[cited by applicant]
US 6261823B1
· Tang
· 2001
[cited by applicant]
US 6281823B1
· Gross, Jr.
· 2001
[cited by applicant]
US 6485958B2
· Blanche
· 2002
[cited by applicant]
US 7270811B2
· Bout
· 2007
[cited by applicant]
US 7326555B2
· Konz, Jr.
· 2008
[cited by applicant]
US 8225289B2
· Burton
· 2012
[cited by applicant]
US 8485958B2
· Nash
· 2013
[cited by applicant]
US 8568719B2
· Williamson
· 2013
[cited by examiner]
US 8772256B2
· Graham
· 2014
[cited by applicant]
US 8772258B2
· Kirkpatrick
· 2014
[cited by applicant]
US 8932607B2
· Custers
· 2015
[cited by applicant]
US 9139642B2
· Williamson
· 2015
[cited by examiner]
US 20100261155A1
· Peeples et al.
· 2010
[cited by applicant]
US 20110305727A1
· Swanson
· 2011
[cited by applicant]
US 20120164176A1
· Swanson
· 2012
[cited by applicant]
US 20120315270A1
· McLellan
· 2012
[cited by applicant]
US 20140248314A1
· Swanson
· 2014
[cited by applicant]
US 20140271899A1
· Leiter
· 2014
[cited by applicant]
US 20210101940A1
· Langedijk
· 2021
[cited by applicant]
US 20210284698A1
· Langedijk
· 2021
[cited by applicant]
US 20220125910A1
· Godeaux
· 2022
[cited by applicant]
US 20220133878A1
· Widjojoatmodjo
· 2022
[cited by applicant]
US 20220193219A1
· Callendret
· 2022
[cited by applicant]
US 20220273787A1
· Callendret
· 2022
[cited by applicant]
CN 109069612
· 2018
[cited by applicant]
EP 0853660A1
· 1998
[cited by applicant]
EP 1230354B1
· 2002
[cited by applicant]
JP 2015512380
· 2015
[cited by applicant]
JP 2015171378
· 2015
[cited by applicant]
KR 20140138765
· 2014
[cited by applicant]
NO 2016040556
· 2016
[cited by applicant]
WO 9003184
· 1990
[cited by applicant]
WO 9014837
· 1990
[cited by applicant]
WO 9609378
· 1996
[cited by applicant]
WO 9611711
· 1996
[cited by applicant]
WO 9822588A2
· 1998
[cited by applicant]
WO 9839411A1
· 1998
[cited by applicant]
WO 9912568A1
· 1999
[cited by applicant]
WO 9941416A2
· 1999
[cited by applicant]
WO 200029024A1
· 2000
[cited by applicant]
WO 200032754A1
· 2000
[cited by applicant]
WO 200070071A1
· 2000
[cited by applicant]
WO 200166137A1
· 2001
[cited by applicant]
WO 2001085984A1
· 2001
[cited by applicant]
WO 200240665A2
· 2002
[cited by applicant]
WO 03040178A1
· 2003
[cited by applicant]
WO 2003049763A1
· 2003
[cited by applicant]
WO 2003061708A1
· 2003
[cited by applicant]
WO 2003078592A2
· 2003
[cited by applicant]
WO 2003104467A1
· 2003
[cited by applicant]
WO 2004001032A2
· 2003
[cited by applicant]
WO 2004004762
· 2004
[cited by applicant]
WO 2004020971A2
· 2004
[cited by applicant]
WO 2005002620
· 2005
[cited by applicant]
WO 2005071093A2
· 2005
[cited by applicant]
WO 2005080556A2
· 2005
[cited by applicant]
WO 2005091804A2
· 2005
[cited by applicant]
WO 2006108707A1
· 2006
[cited by applicant]
WO 2007104792A2
· 2007
[cited by applicant]
WO 2007110409A1
· 2007
[cited by applicant]
WO 2008154456
· 2008
[cited by applicant]
WO WO2008154456A2
· 2008
[cited by examiner]
WO 200911713A1
· 2009
[cited by applicant]
WO 2009079796
· 2009
[cited by applicant]
WO 2009106580A1
· 2009
[cited by applicant]
WO 2010060719A1
· 2010
[cited by applicant]
WO 2010080719A1
· 2010
[cited by applicant]
WO 2010086189A2
· 2010
[cited by applicant]
WO 20101149745
· 2010
[cited by applicant]
WO 2011020079A1
· 2011
[cited by applicant]
WO 20101149743
· 2011
[cited by applicant]
WO 2011045378A1
· 2011
[cited by applicant]
WO 2011045381A1
· 2011
[cited by applicant]
WO 2011050168A2
· 2011
[cited by applicant]
WO 2011098592A1
· 2011
[cited by applicant]
WO 2012006596
· 2012
[cited by applicant]
WO 2012158613
· 2012
[cited by applicant]
WO 2013135615A1
· 2013
[cited by applicant]
WO 2013139911A1
· 2013
[cited by applicant]
WO 2013139916A1
· 2013
[cited by applicant]
WO 2014005643A1
· 2014
[cited by applicant]
WO 2014077096
· 2014
[cited by applicant]
WO WO2014152534A1
· 2014
[cited by examiner]
WO 2014160463
· 2014
[cited by applicant]
WO 2014174018
· 2014
[cited by applicant]
WO WO2014160463A1
· 2014
[cited by examiner]
WO 2014202570
· 2014
[cited by applicant]
WO 2015013551A1
· 2015
[cited by applicant]
WO 2015040002A1
· 2015
[cited by applicant]
WO 2015189425
· 2015
[cited by applicant]
WO 2017005844
· 2017
[cited by applicant]
WO 2017005848
· 2017
[cited by applicant]
WO 2017075125
· 2017
[cited by applicant]
WO WO2017075125A1
· 2017
[cited by examiner]
WO 2017172890
· 2017
[cited by applicant]
WO 2017174568
· 2017
[cited by applicant]
WO 2017174564A1
· 2017
[cited by applicant]
WO WO2017172890A1
· 2017
[cited by examiner]
WO 2017207480
· 2017
[cited by applicant]
WO WO2017207477A1
· 2017
[cited by examiner]
WO 2019053109
· 2019
[cited by applicant]
WO 2021198413
· 2021
[cited by applicant]
WO 2022002894
· 2022
[cited by applicant]
Krarup et al., “A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism,” Nature Comm. 6:8143, (2015).
[cited by applicant]
Kumaria et al., “Whole genome characterization of non-tissue culture adapted HRSV strains in severely infected children,” Virology Journal, 8:372, (2011).
[cited by applicant]
Letarov et al., “The Carboxy-Terminal Domain Initiates Trimerization of Bacteriophage T4 Fibritin,” Biochemistry Moscow, 64:817-823, (1993).
[cited by applicant]
McLellan, et al., “Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus,” Science 342, 592-598, (2013).
[cited by applicant]
McLellan, et al., “Structural basis of respiratory syncytial virus neutralization by motavizumab,” Nat Struct Mol Biol 17(2):248-250, (2010).
[cited by applicant]
McLellan, et al., Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody, Science 340, 1113-1117, (2013).
[cited by applicant]
Guthe et al., “Very Fast Folding and Association of a Trimerization Domain from Bacteriophage T4 Fibritin,” J. Mol. Biol. 337: 905-915, (2004).
[cited by applicant]
Swanson, et al. “Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers,” PNAS, 108(23): 9619-9624, (2011).
[cited by applicant]
Tissue Culture, Academic Press, Kruse and Paterson, editors (1973), and R.I. Freshney, Culture of animal cells: A manual of basic technique, fourth edition (Wiley-Liss Inc., 2000, ISBN 0-471-34889-9).
[cited by applicant]
Remington's Pharmaceutical Sciences, 18th edition, A. R. Gennaro, Ed., Mack Publishing Company [1990].
[cited by applicant]
Pharmaceutical Formulation Development of Peptides and Proteins, S. Frokjaer and L. Hovgaard, Eds., Taylor & Francis [2000].
[cited by applicant]
Handbook of Pharmaceutical Excipients, 3rd edition, A. Kibbe, Ed., Pharmaceutical Press [2000]).
[cited by applicant]
Vered Kunik et al: “Structural Consensus among Antibodies Defines the Antigen Binding Site”, PLOS Computational Biology, vol. 8, No. 2, Feb. 23, 2012 (Feb. 23, 2012), p. e1002388.
[cited by applicant]
Brough et al, “A Gene Transfer Vector-Cell Line System for Complete Functional Complementation of Adenovirus Early Regions E1 and E4,” Journal of Virology, vol. 70, No. 9, pp. 6497-6501 (Sep. 1996).
[cited by applicant]
Altaras et al, “Production and Formulation of Adenovirus Vectors,” Advances in Biochemical Engineering / Biotechnology, vol. 99, pp. 193-260 (2005).
[cited by applicant]
Abrahamsen et al, “Construction of an Adenovirus Type 7a E1A-Vector,” Journal of Virology, vol. 71, No. 11, pp. 8946-8951 (Nov. 1997).
[cited by applicant]
Abbink, Peter et al. “Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D,” Journal of Virology, issue 81, issue 9 (May 2007) pp. 4654-4663.
[cited by applicant]
“Database UniProt Accession W8CJC7,” http://ibis.internal.epo.org/exam/dbfetch.jsp?id=UNIPROT:W8CJC7, Download date: Aug. 12, 2015, 1 page.
[cited by applicant]
Comparison to Sequence 16, U.S. Appl. No. 12/517,194; U.S. Pat. No. 8,772,256 (Year: 2014) 4 pages.
[cited by applicant]
International Search Report and Written Opinion issued in PCT/EP2017/062875, dated Aug. 14, 2017, 10 pages.
[cited by applicant]
Hotard et al., “Identification of Residues in the Human Respiratory Syncytial Virus Fusion Protein That Modulate Fusion Activity and Pathogenesis”, Journal of Virology, Jan. 2015, vol. 89, No. 1, pp. 512-522.
[cited by applicant]
U.S. Appl. No. 17/594,394, filed Oct. 14, 2021. Inventor, Benoit Christophe Stephan Callendret.
[cited by applicant]
U.S. Appl. No. 17/595,255, filed Nov. 12, 2021. Inventor, Benoit Christophe Stephan Callendret.
[cited by applicant]
U.S. Appl. No. 17/664,290, filed May 20, 2022, Inventors: Langedijk, Johannes; Verhagen, Janneke M.
[cited by applicant]
Anonymous, “History of Changes for Study: NCT03334695,” Dec. 5, 2018, Retrieved from the Internet: URL: https://clincaltrials.gov/ct2/history/NCT03334695?V_8-View#StudyPageTop retrived Jul. 7, 2020.
[cited by applicant]
International Search Report issued Jul. 27, 2020 in PCT/EP2020/063408.
[cited by applicant]
Williams Kristi et al, “Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine with an Adenovirus 26 Vector Encoding Pre-Fusion F (Ad26.RSV.preF) in adults 60 years and older.”, The Journal of …
[cited by applicant]
Written Opinion issued Jul. 27, 2020 in PCT/EP2020/063408.
[cited by applicant]
D. Roymans et al: “Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein”, Proceedings of the National Academy of Sciences, v…
[cited by applicant]
Rutten, Lucy et al. “Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers,” Cell Reports, vol. 30, issue 13 (Mar. 2020) pp. 4540-4550.
[cited by applicant]
Ernst J T et al: “Design of a protein surface antagonist based on alpha-helix mimicry: inhibition of gp41 assembly and viral fusion”, Angewandte Chemie, Wiley-VCH, DE, vol. 41, No. 2, Jan. 1, 2002 (Jan. 1, 2002), pp. 27…
[cited by applicant]
Asim K Debnath: “Progress in identifying peptides and small-molecule inhibitors targeted to gp41 of HIV-1”, Expert Opinion On Investigational Drugs, vol. 15, No. 5, Apr. 24, 2006 (Apr. 24, 2006), pp. 465-478, XP05573673…
[cited by applicant]
Rameshwar U. Kadam et al: “Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol”, Proceedings of the National Academy of Sciences, vol. 114, No. 2, Dec. 21, 2016 (Dec. 21, 2016), pp. 206-2…
[cited by applicant]
Takao Hashiguchi et al: “Structures of the prefusion form of measles virus fusion protein in complex with inhibitors”, Proceedings of the National Academy of Sciences, vol. 115, No. 10, Feb. 20, 2018 (Feb. 20, 2018), pp…
[cited by applicant]
Hall et al., J Infect Dis. 1991:163;693-698.
[cited by applicant]
Nair et al., Lancet. 2010:375;1545-1555.
[cited by applicant]
Falsey et al., N Engl J Med. 2005:352;1749-1759.
[cited by applicant]
Falsey et al., Clin Microbiol Rev. 2000:13;371-384.
[cited by applicant]
Thompson et al, “Mortality Associated with Influenza and Respiratory Syncytial Virus in the United States,” JAMA, vol. 289, No. 2, pp. 179-186 (Jan. 2003).
[cited by applicant]
American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increa…
[cited by applicant]
Chin et al., Am J Epidemiol. 1969:89;449-463.
[cited by applicant]
Fulginiti et al., Am J Epidemiol. 1969:89;435-448.
[cited by applicant]
Kapikian et al., Am J Epidemiol. 1969:89;405-421.
[cited by applicant]
Kim et al., Am J Epidemiol. 1969:89;422-434.
[cited by applicant]
Beeler et al., Microb Pathog. 2013:55;9-15.
[cited by applicant]
Connors et al., J Virol. 1992:66;7444-7451.
[cited by applicant]
De Swart et al., J Virol. 2002:76;11561-11569.
[cited by applicant]
Graham et al., J Immunol. 1993:151;2032-2040.
[cited by applicant]
Kim et al., Pediatr Res. 1976:10;75-78.
[cited by applicant]
Murphy et al., J Clin Microbiol. 1986:24;197-202.
[cited by applicant]
Murphy et al., J Clin Microbiol. 1988:26;1595-1597.
[cited by applicant]
Polack et al., J Exp Med. 2002:196;859-865.
[cited by applicant]
Moghaddam et al., Nat Med. 2006:12;905-907.
[cited by applicant]
Belshe et al., J Infect Dis. 2004:190;2096-2103.
[cited by applicant]
Karron et al., J Infect Dis. 2005:191;1093-1104.
[cited by applicant]
Luongo et al., Vaccine. 2009:27;5667-5676.
[cited by applicant]
Shay et al., JAMA. 1999:282;1440-1446.
[cited by applicant]
Graham, Immunol Rev. 2011:239;149-166.
[cited by applicant]
Feltes et al., Pediatr Res. 2011:70;186-191.
[cited by applicant]
Groothuis et al., J Infect Dis. 1998:177;467-469.
[cited by applicant]
Groothuis et al., N Engl J Med. 1993:329;1524-1530.
[cited by applicant]
De Bree et al., J Infect Dis. 2005:191;1710-1718.
[cited by applicant]
Lee et al., Mech Ageing Dev. 2005:126;1223-1229.
[cited by applicant]
Gilman et al., “Rapid profiling of RSV antibody repertories from the memory B cells of naturally infected adult donors”, Science Immunology, 11 pages, Dec. 2016.
[cited by applicant]
Openshaw et al., “Protective and Harmful Immunity to RSV Infection”, Annu Rev. Immunol, vol. 35, pp. 501-532, 2017.
[cited by applicant]
Janssen Vaccines & Prevention B.V.: A Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Vaccinations of Ad26.RSV. preF One Year Apart in Adults Aged 60 Years and Older in Stable Health, Oct. 2016, ret…
[cited by applicant]
Int'l Search Report and Written Opinion issued Dec. 17, 2018 in Int'l Application No. PCT/EP2018/074710, 14 pages.
[cited by applicant]
Bangari, Dinesh et al. “Development of nonhuman adenoviruses as vaccine vectors,” Vaccine, vol. 24 (Feb. 2006) pp. 849-862.
[cited by applicant]
Cohen, Christopher J. et al., “Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor,” Journal of General Virology, vol. 83 (2002) pp. 151-155.
[cited by applicant]
Farina, Steven F. et al. “Replication-Defective Vector Based on a Chimpanzee Adenovirus,” 2001, Journal of Virology, vol. 75, issue 23 (Dec. 2001) pp. 11603-11613.
[cited by applicant]
Kobinger, Gary P. et al. “Chimpanzee adenovirus vaccine protects against Zaire Ebola virus,” Virology, vol. 346, issue 2 (Mar. 2006) pp. 346: 394-401.
[cited by applicant]
Lasaro, Marcio et al. “New insights on adenovirus as vaccine vectors,” Molecular Therapy, vol. 17, issue 8 (Aug. 2009) pp. 1333-1339.
[cited by applicant]
Tatsis, Nia et al., “A CD46-binding chimpanzee adenovirus vector as a vaccine carrier,” Molecular Therapy, vol. 15, issue 3 (Mar. 2007) pp. 608-617.
[cited by applicant]
Widjojoatmodjo Myra N et al, “Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rat…
[cited by applicant]
C A Green et al, “Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an …
[cited by applicant]
T. Grunwald et al, “Novel Vaccine Regimen Elicits Strong Airway Immune Responses and Control of Respiratory Syncytial Virus in Nonhuman Primates”, Journal of Virology., US, (Apr. 15, 2014), vol. 88, No. 8, doi:10.1128/J…
[cited by applicant]
Int'l Search Report and Written Opinion issued Sep. 8, 2018 in Int'l Application No. PCT/EP2018/062604, 6 pages.
[cited by applicant]
Yu et al, “Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection,” Journal of Virology, vol. 82, No. 5, pp. 2350-2357 (Mar. 20…
[cited by applicant]
Yin et al., “Structure of the Parainfluenza Virus 5 F Protein in its Metastable, Prefusion Conformation,” Nature, vol. 439, pp. 38-44 (Jan. 5, 2006).
[cited by applicant]
Written Opinion dated Oct. 12, 2016 in Int'l Application No. PCT/EP2016/066098, 6 pages.
[cited by applicant]
Written Opinion dated Oct. 10, 2016 in Int'l Application No. PCT/EP2016/066104, 8 pages.
[cited by applicant]
Ivy Widjaja et al, “Recombinant Soluble Respiratory Syncytial Virus F Protein That Lacks Heptad Repeat B, Contains a GCN4 Trimerization Motif and Is Not Cleaved Displays Prefusion-Like Characteristics”, PLOS One, Public…
[cited by applicant]
Vogels et al, “Replication-Deficient Human Adenovirus Type 35 Vectors for Gene Transfer and Vaccination: Efficient Human Cell Infection and Bypass of Preexisting Adenovirus Immunity,” Journal of Virology, vol. 77, No. 1…
[cited by applicant]
Suzuki et al., “An Isoleucine Zipper Peptide Forms a Native-like Triple Stranded Coiled Coil in Solution,” Protein Engineering, vol. 11, No. 11, pp. 1051-1055 (1998).
[cited by applicant]
Ogun, S., et al., “The Oligomerization Domain of C4-Binding Protein (C4bp) Acts as an Adjuvant, and the Fusion Protein Comprised of the 19-Kilodalton Merozoite Surface Protein 1 Fused with the Murine C4bp Domain Protect…
[cited by applicant]
Pemberton et al, “Cytoxic T Cell Specificity for Respiratory Syncytial Virus Proteins: Fusion Protein is an Important Target Antigen, Journal of General Virology,” vol. 68, pp. 2177-2182 (1987).
[cited by applicant]
O'Shea et al., “Evidence That the Leucine Zipper is a Coiled Coil,” Science, vol. 243, pp. 538-542 (Jan. 27, 1989).
[cited by applicant]
Ngwuta et al, “Prefusion F-Specific Antibodies Determine the Magnitude of RSV Neutralizing Activity in Human Sera,” Science Translational Medicine, vol. 7, No. 309, pp. 1-9 (2015).
[cited by applicant]
Neuzil, “Progress toward a Respiratory Syncytial Virus Vaccine”, Clinical and Vaccine Immunology, vol. 23, pp. 186-188, 2016.
[cited by applicant]
Nan et al, “Development of an Ad7 cosmid system and generation of an Ad7LE1LE3HIVMN env/rev recombinant virus,” Gene Therapy, vol. 10, pp. 326-336 (2003).
[cited by applicant]
McLellan et al, “Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes,” Journal of Virology, vol. 85, No. 15, pp. 7788-7796 (Aug. 2011…
[cited by applicant]
Magro et al., “Neutralizing Antibodies Against the Preactive Form of Respiratory Syncytial Virus Protein Offer Unique Possibilities for Clinical Intervention,” PNAS, vol. 109, No. 8, pp. 3089-3094 (Feb. 21, 2012).
[cited by applicant]
Krause et al, “A Broadly Neutralizing Human Monclonal Antibody That Recognizes a Conserved, Novel Epitope on the Globular Head of the Influenza H1N1 Virus Hemagglutinin,” Journal of Virology, vol. 85, No. 20, pp. 10905-…
[cited by applicant]
Konz et al, “Serotype Specificity of Adenovirus Purification Using Anion-Exchange Chromatography,” Human Gene Therapy, vol. 16, pp. 1346-1353 (Nov. 2005).
[cited by applicant]
Konz et al, “Scaleable Purification of Adenovirus Vectors,” Methods in Molecular Biology, vol. 434, No. 2, pp. 13-23 (2008).
[cited by applicant]
Kohlmann et al, “Protective Efficacy and Immunology of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus,” Journal of Virology, vol. 83, No. 23, pp. 12601-12610 (Dec. 200…
[cited by applicant]
Kim et al, “Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal immunity against respiratory syncytial virus infection,” Vaccine, vol. 28, pp. 38…
[cited by applicant]
Int'l Search Report dated Oct. 12, 2016 in Int'l Application No. PCT/EP2016/066098, 6 pages.
[cited by applicant]
Int'l Search Report dated Oct. 10, 2016 in Int'l Application No. PCT/EP2016/066104.
[cited by applicant]
Int'l Search Report and Written Opinion dated Oct. 9, 2014 in Int'l Application No. PCT/EP2014/062655, 13 pages.
[cited by applicant]
Int'l Search Report and Written Opinion dated Aug. 12, 2014 in Int'l Application No. PCT/EP2014/058353, 13 pages.
[cited by applicant]
Int'l Search Report and Written Opinion dated Jun. 12, 2017 in Int'l Application No. PCT/EP2017/057962, 17 pages.
[cited by applicant]
Int'l Search Report and Written Opinion dated Jun. 12, 2017 in Int'l Application No. PCT/EP2017/057957, 12 pages.
[cited by applicant]
Hoganson et al, “Development of a Stable Adenoviral Vector Formulation,” BioProcessirig Journal, vol. 1, No. 1, pp. 43-48 (Mar. 2002).
[cited by applicant]
Havenga, M. et al., “Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in Per. C6 cell,” Journal of General Virology, vol. 87 (2006) pp. 2135-2143.
[cited by applicant]
Harbury et al., “A Switch Between Two-, Three-, and Four-Stranded Coiled Coils in GCN4 Leucine Zipper Mutants,” Science, vol. 262, pp. 1401-1407, (1993).
[cited by applicant]
Goerke et al, “Development of a Novel Adenovirus Purification Process Utilizing Selective Precipitation of Cellular DNA,” Biotechnology and Bioengineering, vol. 91, pp. 12-21 (2005).
[cited by applicant]
Gao et al., A Cell Line for High-Yield Production of E1-Deleted Adenovirus Vectors without the Emergence of Replication-Competent Virus, Human Gene Therapy, Jan. 1, 2000, pp. 213-219, vol. 11.
[cited by applicant]
Frits J Fallaux et al., New Helper Cells and Matched Early Region 1-Deleted Adenovirus Vectors Prevent Generation of Replication-Competent Adenoviruses, Human Gene Therapy 9, Sep. 1, 1998, pp. 1909-1917, Mary Ann Lieber…
[cited by applicant]
Database Geneseq (online) “RSV fusion protein N671 S215P, RSV CL57-v224, fibritin, SEQ: 74”, XP002761983, retrieved from EBI accession No. GSP:BBP75438, Database accession No. BBP75438 sequence, Dec. 18, 2014, 1 page.
[cited by applicant]
“Human respiratory syncytial virus, strain RSB89-1734, fusion protein (F) mRNA, complete cds”, EMBL, (Aug. 28, 1995), Database accession No. U31560, URL: EBI, XP002729919, 1 page.
[cited by applicant]
Dames et al., “NMR Structure of a Parallel Homotrimeric Coiled Coil,” Nature Structural Biology, vol. 5, No. 8, pp. 687-691 (Aug. 1998).
[cited by applicant]
Calder et al., “Electron Microscopy of the Human Respiratory Syncytial Virus Fusion Protein and Complexes That it Forms With Monoclonal Antibodies,” Virology, vol. 271, pp. 122-131 (2000).
[cited by applicant]
Looney et al., J Infect Dis. 2002:185;682-685.
[cited by applicant]
Walsh and Falsey, J Infect Dis. 2004:190;373-378.
[cited by applicant]
Hause, Anne M., et al. “Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B.” PLoS One 12.4 (2017): e0175792.
[cited by applicant]
Chen, Xiangpeng, et al. “Genetic variations in the fusion protein of respiratory syncytial virus isolated from children hospitalized with community-acquired pneumonia in China.” Scientific reports 8.1 (2018): 4491.
[cited by applicant]
International Search Report and Written Opinion issued in App. No. PCT/EP2022/054128, dated May 19, 2022, 13 pages.
[cited by applicant]
International Search Report and Written Opinion issued in App. No. PCT/EP2021/058601, dated Sep. 20, 2021, 18 pages.
[cited by applicant]
Int't Search Report and Written Opinion issued Sep. 16, 2021 in Int'l Application PCT/EP2021/067776, 15 pages.
[cited by applicant]