IP Library › Granted Patent US 12,607,406
Granted Patent B2
US 12,607,406 · App. 18/804,734 · Granted Apr 21, 2026

Recombinant virus, composition comprising the same, and uses thereof

Inventors: Chi-Huey Wong (Rancho Santa Fe, CA); Chung-Yi Wu (Taichung, TW)
Assignee: ACADEMIA SINICA
F27D1/12A61K39/12A61K49/00F27B3/14F27B3/24F27D11/08F27D2009/0021
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,607,406
App. No.
18/804,734
Granted
Apr 21, 2026
Kind
B2
Abstract

Immunogenic compositions comprising hemagglutinin (HA) variants and/or neuraminidase (NA) variants, which may be contained in an influenza A virus, and uses thereof for eliciting immune responses against influenza A virus.

Claims (4)

1 . A method of preparing a recombinant Influenza A virus (IAV) comprising a mutant neuraminidase (NA), the method comprising introducing individual plasmids coding for 8 genomic segments of an influenza A virus into a cultured cell, wherein the genomic segment of the NA protein is mutated by introducing a stop codon by site-directed mutagenesis which result in the mutant NA consists of the amino acid sequence of SEQ ID NO: 2.

2 . The method of claim 1 , wherein the recombinant Influenza A virus exhibits reduced virulence relative to a wild-type Influenza A virus.

3 . The method of claim 1 , wherein the recombinant Influenza A virus elicits a CD8 + T-cell immune response upon administration to a subject.

4 . The method of claim 1 , wherein the mutant NA lacks neuraminidase catalytic activity relative to the wild-type neuraminidase of SEQ ID NO: 4.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2024
From: WONG, CHI-HUEY; WU, CHUNG-YI
To: ACADEMIA SINICA
Reel/Frame 068285/0575 →
Continuity (4)
Continuation 17933832 · Sep 20, 2022
Continuation 16348421
Provisional Application 62418800 · Nov 8, 2016
Related Publication 20250137725A1 · May 1, 2025
References Cited (251)
US 5733762A · Midoux et al. · 1998 [cited by applicant]
US 7871626B2 · Hoffmann et al. · 2011 [cited by applicant]
US 8187838B2 · Tsukamoto et al. · 2012 [cited by applicant]
US 10301377B2 · Graham et al. · 2019 [cited by applicant]
US 10906944B2 · He et al. · 2021 [cited by applicant]
US 10953089B1 · Smith et al. · 2021 [cited by applicant]
US 10954289B1 · Babb et al. · 2021 [cited by applicant]
US 11480391B2 · Wong et al. · 2022 [cited by applicant]
US 11866485B2 · Lin et al. · 2024 [cited by applicant]
US 11918641B2 · Wong et al. · 2024 [cited by applicant]
US 11992525B2 · Wong et al. · 2024 [cited by applicant]
US 12085340B2 · Wong et al. · 2024 [cited by applicant]
US 12157763B2 · Lin et al. · 2024 [cited by applicant]
US 12257298B2 · Ma et al. · 2025 [cited by applicant]
US 12318485B2 · Wong et al. · 2025 [cited by applicant]
US 20060073542A1 · Bayer et al. · 2006 [cited by applicant]
US 20100041740A1 · Wong et al. · 2010 [cited by applicant]
US 20100247571A1 · Wong et al. · 2010 [cited by applicant]
US 20130309176A1 · Port et al. · 2013 [cited by applicant]
US 20140107049A1 · Bennani et al. · 2014 [cited by applicant]
US 20150132330A1 · Garcia-Sastre et al. · 2015 [cited by applicant]
US 20160199481A1 · Bloom · 2016 [cited by applicant]
US 20160376321A1 · Hotez et al. · 2016 [cited by applicant]
US 20180043007A1 · LeFebvre et al. · 2018 [cited by applicant]
US 20190388460A1 · Hedrick et al. · 2019 [cited by applicant]
US 20200046826A1 · Wong et al. · 2020 [cited by applicant]
US 20200078452A1 · Wong et al. · 2020 [cited by applicant]
US 20200079808A1 · Pfister et al. · 2020 [cited by applicant]
US 20200231633A1 · Berman et al. · 2020 [cited by applicant]
US 20200283743A1 · Zhang et al. · 2020 [cited by applicant]
US 20210017563A1 · Bhatnagar et al. · 2021 [cited by applicant]
US 20210207106A1 · Anthony et al. · 2021 [cited by applicant]
US 20210316002A1 · Ellis · 2021 [cited by applicant]
US 20210386852A1 · Duprex · 2021 [cited by applicant]
US 20220233713A1 · Callan et al. · 2022 [cited by applicant]
US 20230074185A1 · Wong et al. · 2023 [cited by applicant]
US 20230105209A1 · Lin et al. · 2023 [cited by applicant]
US 20230279080A1 · Lin et al. · 2023 [cited by applicant]
US 20230302114A1 · Wong · 2023 [cited by applicant]
US 20240016917A1 · Ma et al. · 2024 [cited by applicant]
US 20240066113A1 · Wong et al. · 2024 [cited by applicant]
US 20240100147A1 · Wong et al. · 2024 [cited by applicant]
US 20240228591A1 · Lin et al. · 2024 [cited by applicant]
US 20240366516A1 · Wong et al. · 2024 [cited by applicant]
US 20240366517A1 · Wong et al. · 2024 [cited by applicant]
US 20240384320A1 · Wong et al. · 2024 [cited by applicant]
US 20250041222A1 · Wong et al. · 2025 [cited by applicant]
US 20250114446A1 · Wu et al. · 2025 [cited by applicant]
CN 105934441A · 2016 [cited by applicant]
CN 111892648A · 2020 [cited by applicant]
CN 112626124A · 2021 [cited by applicant]
CN 113388011A · 2021 [cited by applicant]
CN 116478948A · 2023 [cited by applicant]
EP 1987068A1 · 2008 [cited by applicant]
EP 2949665A1 · 2015 [cited by applicant]
JP 2012530499A · 2012 [cited by applicant]
JP 2017518989A · 2017 [cited by applicant]
JP 2023541094A · 2023 [cited by applicant]
RU 2720614C1 · 2020 [cited by applicant]
RU 2730897C1 · 2020 [cited by applicant]
WO 2004099240A2 · 2004 [cited by applicant]
WO 2004099240A3 · 2004 [cited by applicant]
WO 2007008918A2 · 2007 [cited by applicant]
WO 2007095506A1 · 2007 [cited by applicant]
WO 2009002516A1 · 2008 [cited by applicant]
WO 2009007427A2 · 2009 [cited by applicant]
WO 2010022737A1 · 2010 [cited by applicant]
WO 2010111687A2 · 2010 [cited by applicant]
WO 2010148511A1 · 2010 [cited by applicant]
WO 2011115862A1 · 2011 [cited by applicant]
WO 2012054907A2 · 2012 [cited by applicant]
WO 2012088428A1 · 2012 [cited by applicant]
WO 2013043729A1 · 2013 [cited by applicant]
WO 2013067652A1 · 2013 [cited by applicant]
WO 2014115797A1 · 2014 [cited by applicant]
WO 2015057942A1 · 2015 [cited by applicant]
WO 2015073727A1 · 2015 [cited by applicant]
WO 2015176662A1 · 2015 [cited by applicant]
WO 2015184004A1 · 2015 [cited by applicant]
WO 2017062496A2 · 2017 [cited by applicant]
WO 2017081082A2 · 2017 [cited by applicant]
WO 2018089407A1 · 2018 [cited by applicant]
WO 2019028190A1 · 2019 [cited by applicant]
WO 2015028478A1 · 2019 [cited by applicant]
WO 2019246363A1 · 2019 [cited by applicant]
WO 2020011275A1 · 2020 [cited by applicant]
WO 2020058239A1 · 2020 [cited by applicant]
WO 2019246363 · 2020 [cited by applicant]
WO 2020172072A1 · 2020 [cited by applicant]
WO 2020198865A1 · 2020 [cited by applicant]
WO 2020205034A1 · 2020 [cited by applicant]
WO 2021019102A2 · 2021 [cited by applicant]
WO 2021035325A1 · 2021 [cited by applicant]
WO 2021045632A1 · 2021 [cited by applicant]
WO 2021045836A1 · 2021 [cited by applicant]
WO 2021174128A1 · 2021 [cited by applicant]
WO 2021180602A1 · 2021 [cited by applicant]
WO 2021183195A1 · 2021 [cited by applicant]
WO 2021186028A1 · 2021 [cited by applicant]
WO 2021214204A1 · 2021 [cited by applicant]
WO 2021219897A1 · 2021 [cited by applicant]
WO 2021226533A1 · 2021 [cited by applicant]
WO 2021233989A1 · 2021 [cited by applicant]
WO 2021257586A1 · 2021 [cited by applicant]
WO 2022047401A1 · 2022 [cited by applicant]
WO 2022221835A2 · 2022 [cited by applicant]
WO 2022221837A2 · 2022 [cited by applicant]
WO 2022227927A1 · 2022 [cited by applicant]
WO 2022229854A1 · 2022 [cited by applicant]
WO 2022231980A1 · 2022 [cited by applicant]
WO PCTUS2282428 · 2022 [cited by applicant]
WO 2023021111A1 · 2023 [cited by applicant]
WO 2023056482A1 · 2023 [cited by applicant]
WO 2023069551A1 · 2023 [cited by applicant]
WO 2023129928A2 · 2023 [cited by applicant]
WO PCTUS2434588 · 2024 [cited by applicant]
WO 2024215612A2 · 2024 [cited by applicant]
WO 2024215614A2 · 2024 [cited by applicant]
WO 2024215616A2 · 2024 [cited by applicant]
WO PCTUS2460715 · 2024 [cited by applicant]
Huang et al., “Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models,” Sci Transl Med., Apr. 6, 2022, vol. 14(639):eabm0899. [cited by applicant]
Huang, Han-Yi et al., “Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models,” Sci. Transl. Med., vol. 14, eabm0899, (2022), 13 pages. [cited by applicant]
Hughes et al., “Adaptation of Influenza A Viruses to Cells Expressing Low Levels of Sialic Acid Leads to Loss of Neuraminidase Activity”, Journal of Virology, 2001, vol. 75, No. 8, pp. 3766-3770. [cited by applicant]
International Search Report and Written Opinion issued on Jun. 22, 2023 in International Patent Application No. PCT/US22/82428. [cited by applicant]
Janeway Jr., Charles A et al., “Immunobiology: The Immune System in Health and Disease,” 3rd edition, Garland Publishing Inc., 1997, pp. 3:1-3:11. [cited by applicant]
Kanyavuz, Alexia et al., “Breaking the law: unconventional strategies for antibody diversification,” Nat Rev Immunol., Jun. 2019, 19(6):355-368. doi: 10.1038/S41577-019-0126-7. PMID: 30718829. [cited by applicant]
Krammer, Florian et al., “Chimeric Hemagglutinin Influenza Virus Vaccine Constructs Elicit Broadly Protective Stalk-Specific Antibodies,” Journal of Virology, Jun. 2013, vol. 87, No. 12, pp. 6542-6550. [cited by applicant]
Kurzawa, Timon, “1,1,2,2,3,3,4,4,4-Nonafluorobutane-1-sulfonyl fluoride (NfF),” Synlett, 2015, vol. 26, pp. 1422-1423. [cited by applicant]
Lescar et al., “Crystal Structure of a Cross-reaction Complex between Fab F9.13.7 and Guinea Fowl Lysozyme,” J Biol Chem., Jul. 1995, 270(30):18067-76. doi: 10.1074/jbc.270.30.18067. PMID: 7629116. [cited by applicant]
Levit, Mariia et al., “Bio-Inspired Amphiphilic Block-Copolymers Based on Synthetic Glycopolymer and Poly(Amino Acid) as Potential Drug Delivery Systems,” Polymers, 2020, vol. 12, pp. 183 (27 pages). doi:10.3390/polym12… [cited by applicant]
Li, et al., Glycosylation of Neuraminidase Determines the Neurovirulence of Influenza A/WSN/33 Virus, 1993, Journal of Virology, vol. 67, No. 11, pp. 6667-6673. [cited by applicant]
Liu, Wen-Chun et al., “Unmasking Stem-Specific Neutralizing Epitopes by Abolishing N-Linked Glycosylation Sites of Influenza Virus Hemagglutinin Proteins for Vaccine Design”, Journal of Virology, vol. 90 No. 19, Oct. 20… [cited by applicant]
Lloyd, C. et al., “Modelling the human immune response: performance of a 10(11) human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Engineering Design & Selection, 2009, vol. 2… [cited by applicant]
Lo, H.-J. et al., “Synthesis of Sialidase-Resistant Oligosaccharide and Antibody Glycoform Containing α2,6-Linked 3Fax-Neu5Ac”, J. Am. Chem. Soc., Apr. 10, 2019, vol. 141, No. 16, pp. 6484-6488. (Whole Document.). [cited by applicant]
Lostale-Seijo, Irene and Montenegro, Javier, “Synthetic materials at the forefront of gene delivery,” Nature Reviews Chemistry, vol. 2, Sep. 21, 2018, pp. 258-277. [cited by applicant]
Ma et al., “The Role of Glucose Transporters in the Distribution of p-aminophenyl mannppyranose modified liposomes within mice brains,” Journal of Controlled Release, 182, pp. 99-110. (Year: 2014). [cited by applicant]
Magazine, Nicholas et al., “Mutations and Evolution of the SARS-CoV-2 Spike Protein,” Viruses, 2022, vol. 14, 640, 11 pgs. [cited by applicant]
Medina, Rafael A. et al., “Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses”, Sci Transl Med., May 29, 2013. [cited by applicant]
Nobusawa et al., “Comparison of Complete Amino Acid Sequences and Receptor-Binding Properties among 13 Serotypes of Hemagglutinins of Influenza A Viruses”, Virology, 182, 475-485 (1991). [cited by applicant]
Non-Final Office Action issued in U.S. Appl. No. 17/937,744 dated Jul. 5, 2023. [cited by applicant]
Office Action and Search Report issued in Taiwan Patent Application No. 111113933 on Mar. 26, 2024. English translation of search report. [cited by applicant]
Office Action issued in Taiwan Patent Application No. 111113932 on Oct. 16, 2023. [cited by applicant]
Office Action issued on Nov. 14, 2022, in Israel Patent Application No. 293502. [cited by applicant]
Official Action, dated Aug. 31, 2023, received in Russia Patent Application No. 2023100504. English translation provided. [cited by applicant]
Okamoto, K. et al., “An effective synthesis of α-glycosides of N-acetylneuraminic acid by use of 2β-halo-3β-hydroxy-4,7,8,9-tetra-O-acetyl-N-acetylneuraminic acid methyl ester”, Tetrahedron Letters, 1986, vol. 27, No. 4… [cited by applicant]
Pappalardo, Juan Sebastian et al., “Characterization of a Nanovaccine Platform Based on an [alpha]1,2-Mannobiose Derivative Shows Species-non-specific Targeting to Human, Bovine, Mouse, and Teleost Fish Dendritic Cells,… [cited by applicant]
Rahman, M Shaminur et al., “Epitope-based chimeric peptide vaccine design against S, M, and E proteins of SARS-CoV-2, the etiologic agent of COVID-19 pandemic, an in silico approach”, PeerJ, Jul. 27, 2020 (publication d… [cited by applicant]
Rees-Spear, Chloe et al., “The effect of spike mutations on SARS-CoV-2 neutralization,” Cell Rep., Mar. 2023, 34(12): 108890. Published online Mar. 6, 2021. doi: 10.1016/j.celrep.2021.108890: 10.1016/j.celrep.2021.10889… [cited by applicant]
Roberts, Paul C. et al., “Role of Conserved Glycosylation Sites in Maturation and Transport of Influenza A Virus Hemagglutinin”, Journal of Virology, Jun. 1993, p. 3048-3060. [cited by applicant]
Rudikoff et al., “Single amino acid substitution altering antigen-binding specificity,” Proc. Natl Acad Sci U S A, Mar. 1982, vol. 79(6), pp. 1979-1983. doi: 10.1073/pnas.79.6.1979. PC/D: 6804947. [cited by applicant]
Sanda, Miloslav et al., “N- and O-Glycosylation of the SARS-CoV-2 Spike Protein,” Anal. Chem., vol. 93, No. 4, Jan. 7, 2021, pp. 2003-2009. [cited by applicant]
Search Report, dated Aug. 31, 2023, received in Russia Patent Application No. 2023100504. [cited by applicant]
Shin et al., “CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome,” Nature Communications, 2017, vol. 8, Art. 15464. [cited by applicant]
Shivatare, Vidya et al., “Study on antibody Pc-glycosylation for optimal effector functions,” Chem Commun (Camb), 2024, vol. 59, iss. 37, pp. 5555-5558. doi:10.1039/d3cc00672g. [cited by applicant]
Sun et al., “N-Linked Glycosylation of the Hemagglutinin Protein Influences Virulence and Antigenicity of the 1918 Pandemic and Seasonal H1N1 Influenza A Viruses”, 2013, Journal of Virology, vol. 87, No. 15, pp. 8756-87… [cited by applicant]
Tai, Wanbo et al., “Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine,” Cell Mol Immunol. Jun. 2020; … [cited by applicant]
Tian, Jing-Hui et al., “SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice,” Nature Communications, 2021, 14 pages. Downloaded Sep. 27, 2023: https://doi.org/10.… [cited by applicant]
Torres-Vanegas, Julian D., “Delivery Systems for Nucleic Acids and Proteins: Barriers, Cell Capture Pathways and Nanocarriers,” Pharmaceutics, vol. 13, No. 3, Mar. 22, 2021, pp. 428. [cited by applicant]
Vogel, Annette B. et al. “BNT162b vaccines protect rhesus macaques from SARS-CoV-2,” Nature, vol. 592, Feb. 1, 2021, pp. 283-289. [cited by applicant]
Wang, Ce et al., “Lymphatic-targeted cationic liposomes: A robust vaccine adjuvant for promoting long-term immunological memory,” Vaccine, 2014, vol. 32, 5475-5483. [cited by applicant]
Wang, Ce et al., Supplementary Data, 2014, Vaccine, 32, 5475-5483. [cited by applicant]
Wang, Qiong et al., “Antibody glycoengineering strategies in mammalian cells,” Biotechnology and Bioengineering, 2018, vol. 115:1378-1393. [cited by applicant]
Wang, Shih-Chi et al., “Development of a universal influenza vaccine using hemagglutinin stem protein produced from Pichia pastoris,” Virology, 2019, vol. 526, pp. 125-137. [cited by applicant]
Watanabe, Yasunori et al., “Exploitation of glycosylation in enveloped virus pathobiology,” BBA—General Subjects 1863, 2019), pp. 1480-1497. [cited by applicant]
Watanabe, Yasunori et al., “Site-specific glycan analysis of the SARS-CoV-2 spike,” Science, Jul. 2020, vol. 369, pp. 330-333. [cited by applicant]
Weissman, Drew et al., “D614G Spike Mutation Increases Sars CoV-2 Susceptibility to Neutralization,” Cell Host & Microbe, Jan. 13, 2021, vol. 29, pp. 23-31 (e1-e4). [cited by applicant]
Wu, Chung-Yi et al., “Glycosite-deleted mRNA of SARS-CoV-2 spike protein as a broad-spectrum vaccine,” PNAS, 2022, vol. 119, No. 9. https://doi.irg/10.1073/pnas.2119995119. [cited by applicant]
Wu, Chung-Yi et al., “Influenza A surface glycosylation and vaccine design”, PNAS, Jan. 2017, (Epub Dec. 27, 2016), vol. 114, No. 2, pp. 280-285. [cited by applicant]
Yang et al., “Glucoproteomic Characterization of FUT8 Knock-Out Cells Reveals Roles of FUT8 in the Glycosylation,” Frontiers in Chemistry, Oct. 28, 2021, vol. 9, No. 755238, pp. 1-9, entire document. [cited by applicant]
Yang, Zhiwei et al., “Mutation effects of neuraminidases and their docking with ligands: a molecular dynamics and free energy calculation study”, J Comput Aided Mol Des, 27: 935-950, 2013. [cited by applicant]
Zaraket, Hassan et al., “Full Genome Characterization of Human Influenza A/H3N2 Isolates from Asian Countries Reveals a Rare Amantadine Resistance-Conferring Mutation and Novel PB1-F2 Polymorphisms”, Frontiers in Microb… [cited by applicant]
Zhang, Penghui et al., “Engineering the Surface of Smart Nanocarriers Using a pH-/Thermal-/GSH-Responsive Polymer Zipper for Precise Tumor Targeting Therapy in Vivo,” Advanced Materials, 2017, vol. 29, 1702311 (10 pages… [cited by applicant]
Zhang, Ruhe et al., “Poly(disulfide)s: From Synthesis to Drug Delivery,” Bio Macromolecules, 2022, vol. 23, pp. 1-19. [cited by applicant]
Zhang, Xiaojian et al., “Role of stem glycans attached haemagglutinin in the biological characteristics of H5N1 avian influenza virus”, Journal of General Virology, 96, 1248-1257, 2015. [cited by applicant]
Zhang, Yan et al., “Glycosylation on Hemagglutinin Affects the Virulence and Pathogenicity of Pandemic H1N1/2009 Influenza A Virus in Mice”, Plos One, vol. 8, Issue 4, Apr. 2013. [cited by applicant]
Zhang, Yong et al., “Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins,” Mol Cell Proteomics, 2021, vol. 20, 100058. https://doi.org/10.1074/mcp.RA120.002295. [cited by applicant]
Zhao, “Glycans of SARS-CoV-2 Spike Protein in Virus Infection and Antibody Production”, Frontiers in Molecular Biosciences, Apr. 13, 2021; Entire Document; DOI: 10.3389/fmolb.2021.629873. [cited by applicant]
Zheng, J. et al., “Identification of N-linked glycosylation sites in the spike protein and their functional impact on the replication and infectivity of coronavirus infectious bronchitis virus in cell culture”, Virology… [cited by applicant]
Okamoto, K. et al., “An effective synthesis of a-glycosides of N-acetylneuraminic acid by use of 2β-halo-3β-hydroxy-4,7,8,9-tetra-O-acetyl-N-acetylneuraminic acid methyl ester”, Tetrahedron Letters, 1986, vol. 27, No. 4… [cited by applicant]
U.S. Appl. No. 17/937,744, filed Oct. 3, 2022, Kuo-I Lin. [cited by applicant]
U.S. Appl. No. 17/998,208, filed Nov. 8, 2022, Chi-Huey Wong. [cited by applicant]
U.S. Appl. No. 18/005,573, filed Jan. 13, 2023, Che Ma. [cited by applicant]
U.S. Appl. No. 18/029,758, filed Mar. 31, 2023, Chi-Huey Wong. [cited by applicant]
U.S. Appl. No. 18/146,873, filed Dec. 27, 2022, Kuo-I Lin. [cited by applicant]
U.S. Appl. No. 63/266,008, filed Dec. 27, 2021, Kuo-I Lin. [cited by applicant]
U.S. Appl. No. 63/549,343, filed Feb. 2, 2024, Chi-Huey Wong. [cited by applicant]
U.S. Appl. No. 63/588,932, filed Oct. 9, 2023, Chi-Huey Wong. [cited by applicant]
Alam, MM et al., “Glycan-Modified Virus-Like Particles Evoke T Helper Type 1-Like Immune Responses,” ACS Nano, vol. 15, No. 1, Jan. 26, 2021, published online Aug. 17, 2020, doi: 10.1021/acsnano.0c03023, pp. 309-321; (p… [cited by applicant]
Avinash, MB et al., “Nanoarchitectonics of biomolecular assemblies for functional applications,” Nanoscale, vol. 6, No. 22, Nov. 21, 2014, doi: 10.1039/c4nr04340e, pp. 13348-13369. (p. 18, figure 13c). [cited by applicant]
Bang, Eun-Kyoung et al., JACS, 2013, vol. 135, pp. 2088-2091. dx.doi.org/10.1021/ja311961k. [cited by applicant]
Bej, Raju et al., “Disulfide chemistry in responsive aggregation of amphiphilic systems,” Royal Society of Chemistry, 2020, vol. 16, pp. 11-26. DOI: 10.1039/C9SM01960J. [cited by applicant]
Bellato, Frederica, “Targeting dendritic cells with mannosylated cationic glycopolymers for nucleic acid-mediated cancer immunotherapy,” UNITesi, Magazzini Digitali, 2019, 25 pages. (https://tesidottorato.depositolegale… [cited by applicant]
Bennua-Skalmowski, B. et al., “A Facile Conversion of Primary or Secondary Alcohols with n-Perfluorobutane-sulfonyl Fluoride/1,8-Diazabicyclo[5.4.0]undec-7-ene into their Corresponding Fleorides,” Tetrahedron Letters, v… [cited by applicant]
Bernstein, David et al., “Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomized, placebo-controlled, phase 1 clinical trial”, The Lancet Infectiou… [cited by applicant]
Bosch, Berend Jan et al.,“Coronavirus Escape from Heptad Repeat 2 (HR2)-Derived Peptide Entry Inhibition as a Result of Mutations in the HR1 Domain of the Spike Fusion Protein,” J of Virol., Mar. 2008, vol. 82, No. 5, p… [cited by applicant]
Byrne et al., “CRISPR/Cas9 gene editing for the creation of an MGAT1-deficient CHO cell line to control HIV-1 vaccine glycosylation,” PLOS Biology, 2018, vol. 16, No. 8: e2005817. [cited by applicant]
Cao, Yiwei et al., “Dynamic Interactions of Fully Glycosylated SARS-CoV-2 Spike Protein with Various Antibodies,” JCTC, Sep. 16, 2021, vol. 17, pp. 6559-6569. [cited by applicant]
Castrucci, M.R. et al., “Biologic importance of neuramindase stalk length in influenza A virus”, Journal of Virology, 1993, vol. 67, No. 2, pp. 759-764. [cited by applicant]
Chokhawala, H.A. et al., “Enzymatic Synthesis of Fluorinated Mechanistic Proves for Sialidases and Sialyltransferases”, J.Am. Chem. Soc., 2007, p. 10630; scheme 1. [cited by applicant]
Chokhawala, Harshai A. et al., “Enzymatic Synthesis of Fluorinated Mechanistic Probes for Sialidases and Sialytransferases,” JACS Communications, 2007, vol. 129, pp. 10630-10631. [cited by applicant]
Chuard, Nicolas et al., “Cell-penetrating poly(disulfide)s: the dependence of activity, depolymerization kinetics and intracellular localization on their length,” Organic & Biomolecular Chemistry, 2015, vol. 13, pp. 64-… [cited by applicant]
Dang, Juanjuan et al., “Multivalency-assisted membrane-penetrating siRNA delivery sensitizes photothermal ablation via inhibition of tumor glycolysis metabolism,” Biomaterials, vol. 223, Dec. 2019, 119463. [cited by applicant]
Davies, Nicholas G. et al., “Estimated transmissibility and impact of SARS-CoV-2 lineage B. 1.1.7 in England,” Science, Apr. 2021, vol. 372, pp. 149 (10 pages). [cited by applicant]
Definition of hemagglutinin [Influenza A virus (A/chicken/Jembrana/BPPV6/2004(H5N1))]. GenBank: ABE97562.1. https://www.ncbi.nlm.nih.gov/protein/ABE97562.1?report=genbank&log$=prottop&blast_rank=1&RID=CGUKON57013. [cited by applicant]
Definition of hemagglutinin [Influenza A virus (A/Singapore/GP4444/2010(H1N1))]. GenBank: AEH59357.1. https://www.ncbi.nlm.nih.gov/protein/AEH59357.1?report=genbank&log$=prottop&blast_rank=1&RID=CGTA0JCD016. [cited by applicant]
Ding, Li et al., “A [cited by applicant]
Doboszewski, Bogdan et al., “The rapid synthesis of deoxyfluoro sugars using tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF)1,” 1987, Canadian Journal of Chemistry, 65(2): 412-419. [cited by applicant]
Dowling, W. et al., “Influences of Glycosylation on Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines”, J. of Virology, 2007, vol. 81, No. 4, pp. 1821-1837, p. 1822, second column, fou… [cited by applicant]
Du, Dan et al., “The role of glucose transporters in the distribution of p-aminophenyl-[alpha]-D-mannopyranoside modified liposomes within mice brain,” Journal of Controlled Released, 2014, vol. 182. pp. 99-110. [cited by applicant]
Edwards, et al., “The Remarkable Flexibility of the Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLyS,” J. Mol. Biol., Nov. 2003, 14:334(1):103-18; doi: 10.1016/jmb… [cited by applicant]
Engdahl, Cecilia et al., “Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: a potential explanation for the increased risk of rheumatoid arthritis in postm… [cited by applicant]
Fan, CY et al., “Synthesis of Dendritic Cell-Targeted Polymeric Nanoparticles for Selective Delivery of mRNA Vaccines to Elicit Enhanced Immune Responses,” bioRxiv, Epub: Nov. 14, 2023; pp. 1-12; entire document; DOI: 1… [cited by applicant]
Feng et al., “A Glycolipid Adjuvant, 7DW8-5, Enhances the Protective Immune Response to the Current Slpit Influenza Vaccine in Mice”, Frontiers in Microbiology, Sep. 18, 2019, vol. 10, No. 2157M, pp. 1-9; abstract. [cited by applicant]
Focosi, Daniele, “Neutralising antibody escape of SARS-CoV-2 spike protein: Risk assessment for antibody-based Covid-19 therapeutics and vaccines,” Rev. Med Virol., 2021, vol. 31, 21 pages. e2231. [cited by applicant]
Galili, “Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present alpha-gal epitopes”, Vaccine, Aug. 19, 2020; abstract; Fig. 1; DOI: 10.1016/j.vaccine.2020… [cited by applicant]
Galili, Uri, “Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present [alpha]-gal epitopes, ” Vaccine, 2020, vol. 38, pp. 6487-6499. [cited by applicant]
Galili, Uri, “COVID-19 variants as moving targets and how to sop them by glycoengineered whole-virus vaccines,” Virulence, 12:1, 1717-1720, DOI: 10.1080/21505594.2021.1939924. (https://doi.org/10.1080/21505594.2021.1939… [cited by applicant]
Geisler, Christoph et al., “Engineering [beta]1,4-galactosyltransferase I to reduce secretion and enhance N-glycan elongation in insect cells,” Journal of Biotechnology, 2015, vol. 193, 52-65 (14 pages). [cited by applicant]
GenBank Accession BCN86353.1 accessed on Jan. 22, 2021. https://www.ncbi.nlm.nih.gov/protein/BCN86353.1?report=genbank&log$=protalign&blast_rank=2&RID=EYKWWEAA016. [cited by applicant]
GenBank Accession CCH23214, haemagglutinin [Influenza A virus (A/WSN/1933(H1N1))], 2013. [cited by applicant]
GenBank accession MN908947.3, Mar. 18, 2020, 11 pages. (https://www.ncbi.nlm.nih.gov/nuccore/MN908947). [cited by applicant]
GenBank Accession NCBI No. QHD43416.1 (surface glycoprotein [Severe acute respiratory syndrome coronavirus 2]; published Mar. 18, 2020. [cited by applicant]
GenBank Accession No. nC_048600.1 (Cricetulus griseus strain 17A/GY chromosome 7, alternate assembly CriGri-PICRH-1.0, whole genome shotgun sequence. Jul. 12, 2020. [cited by applicant]
GenBank Accession, ACF54601, neuraminidase [Influenza A virus (A/WSN/1933(H1N1))], 2008. [cited by applicant]
GenBank Accession: QHD43416.1, (Mar. 18, 2020) [Described in the Office Action as Appendix A] (Year: 2020). [cited by applicant]
GenBank: QLB39105.1 accessed on Jan. 1, 2020. https://www.ncbi.nlm.nih.gov/protein/QLB39105.1?report=genbank&log$=protalign&blast_rank=1&RID=EYKWWEAA016. [cited by applicant]
GenBank: QTA38985.1 accessed Mar. 21, 2021. https://www.ncbi.nlm.nih.gov/protein/QTA38985.1?report=genbank&log$=protalign&blast_rank=3&RID=EYKWWEAA016. [cited by applicant]
Gillian, M. Air, “Influenza neuraminidase”, Influenza and Other Respiratory Viruses, 2011. [cited by applicant]
Goel, Manisha et al., “Plasticity within the Antigen-Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response,” J. Immunol., Dec. 15, 2004, 173(12):7358-67 PMID: 15585860 DOI: 10.4049/jimmunol.173… [cited by applicant]
Gong, Yanqiu et al., “The glycosylation in SARS-CoV-2 and its receptor ACE2,” Signal Transduction and Targeted Therapy, 2021, vol. 6, 396 (24 pages). [cited by applicant]
Goswami, Roshan et al., “Conjugation of Mannans to Enhance the Potency of Liposome Nanoparticles for the Delivery of RNA Vaccines,” Pharmaceutics, 2021, vol. 13, 240, 13 pages. [cited by applicant]
Grant, Oliver C. et al., “Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition,” Scientific Reports, 2020, vol. 10, 14991. https://doi.org/10.1038/s41598-020-71748-7. [cited by applicant]
Gutierrez Reyes, Cristian D., et al. “N-Glycome Profile of the Spike Protein S1: Systemic and Comparative Analysis from Eleven Variants of SARS-CoV-2,” Biomolecules, 2023, vol. 13, pp. 1421 (17 pages). [cited by applicant]
Hayashi, T. et al., “Stereospecific α-Sialylation by SIte-Selective Fluorination”, Agnew. Chem. Int. Ed., Jan. 25, 2019, vol. 58, pp. 3814-3818. (Whole Document). [cited by applicant]
He, P. et al., “Advances in aluminum hydroxide-based adjuvant research and its mechanism,” Human Vaccine and Immunotherapeutics, 2015, vol. 11, iss. 2, pp. 477-488. [cited by applicant]
Hombu, Ryoma et al., “Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems,” Molecules, 2021, vol. 26, 5950 (27 [ages). [cited by applicant]
Huang et al., “Impact of glycosylation on SARS-CoV-2 infection and broadly protective vaccine design,” BioRxiv, May 25, 2021, DOI: https://doi.org/10.1101/2021.05.25.445523, internal pp. 1-48. [cited by applicant]
Casalino, Lorenzo et al., “Beyond Shielding: The ROles of Glycans in the SARS-CoV-2 Spike Protein,” ACS Central Science, 2020, vol. 6, No. 10, pp. 1722-1734. http://pubs.acs.org/journal/acscii. [cited by applicant]
Almaraz, Ruben T. et al., “Metabolic Oligosaccharide Engineering: Implications for Selectin-Mediated Adhesion and Leukocyte Extravasation,” Ann Biomed Eng., Apr. 2012, vol. 40, Art. 4, pp. 806-815. doi: 10.1007/s10439-0… [cited by applicant]
GenBank Accession No. MW560959.1 dated Mar. 21, 2021. www.ncbi.nlm.nih.gov/nucleotide/MW560959.1 (Year: 2021). [cited by applicant]
GenBank Accession No. UPO69279.1 dated Nov. 30, 2021. https://www.ncbi.nlm.nih.gov/protein/UFO69279.1 (Year: 2021). [cited by applicant]
GenBank Accession No. YP_009724390.1 dated Jul. 18, 2020. https://www.ncbi.nlm.nih.gov/protein/YP_009724390.1 (Year: 2020). [cited by applicant]
Huang, Yuan et al., “Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19,” Acta Pharmacologica Sinica, (2020), 41:1141-1149; https://doi.org/10.1038/s41401… [cited by applicant]
UniProt, ID: B4GT-1_HUMAN, P15291, available Oct. 17, 2006 (Year: 2006). [cited by applicant]
Wang, Mingqun et al., “Engineering a bacterial sialyltransferase for di-sialylation of a therapeutic antibody,” Organic & Biomolecular Chemistry, 2020, vol. 18, 2886, 7 pages. DOI: 10.1039/d0ob00276c. [cited by applicant]
Zhou, Daming et al., “Structural basis for the neutralization of SARS-CoV-2 by antibody from convalescent patient,” Nature Structural & Molecular Biology, Oct. 2020, vol. 27, pp. 950 (25 pages). [cited by applicant]
Cao, Yunlong et al., “Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies,” Nature, Dec. 23, 2021, vol. 602, No. 7898, pp. 657-663. XP037700795, DOI: 10.1038/S41586-021-04385-3. [cited by applicant]
Cheng, Cheng-Wei et al., “Low-sugar universal mRNA vaccine against coronavirus variants with deletion of glycosites in the S2 or stem of SARS-CoV-2 spike messenger RNA (mRNA),” PNAS, 2023, vol. 120, No. 49, 8 pages. doi… [cited by applicant]
Sun, Da and Lu, Zheng-Rong, “Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery,” Pharmaceutical Research, (2023), 40:27-46. https://doi.org/10.1007/s11095-022-03460-2. [cited by applicant]
Chen, Zigui et al., “Genomic and evolutionary comparison between SARS-CoV-2 and other human coronaviruses,” J of Virol. Methods, (2021), vol. 289, 114032, 11 pages. [cited by applicant]
Huang, Han-Wen et al., “Cell-based production of Fc-GIcNAc and Fc-alpha-2,6 sialyl glycan enriched antibody with improved effector functions through glycosylation pathway engineering,” bioRxiv, (Dec. 19, 2023), 11 pages… [cited by applicant]