IP Library › Granted Patent US 12,491,245
Granted Patent B2
US 12,491,245 · App. 17/560,830 · Granted Dec 9, 2025

Antibodies useful in passive influenza immunization, and compositions, combinations and methods for use thereof

Inventors: Angeles Estelles (Belmont, CA); Lawrence M. Kauvar (San Francisco, CA); Adam Vigil (Yonkers, NY); Michael Wittekind (Yonkers, NY)
Assignees: CONTRAFECT CORPORATION; TRELLIS BIOSCIENCE, INC
A61K39/42C07K16/1018A61K2039/505A61K2039/507A61K2039/543C07K2317/33C07K2317/34C07K2317/55C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,491,245
App. No.
17/560,830
Granted
Dec 9, 2025
Kind
B2
Abstract

Antibodies, compositions and methods are provided for treatment and prophylaxis of influenza virus. Antibodies and antigen-binding fragments are provided that bind near the HA 0 maturation cleavage site consensus sequence of influenza hemagglutinin A. Antibody compositions, combinations and methods for effective passive immunization across influenza A and B strains are also provided.

Claims (33)

1 . A pharmaceutical composition formulated for intranasal or inhalation administration and effective for treatment or prophylaxis of influenza viral infection in a subject comprising:

(a) a first antibody or antigen-binding fragment thereof that binds to and/or inhibits influenza virus comprising:

a heavy chain amino acid sequence comprising a heavy chain variable region (HCVR) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 11, a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 12 and a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:13 and

a light chain amino acid sequence comprising a light chain variable region (LCVR) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 14, a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO: 15, and a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO: 16;

(b) a second antibody or antigen-binding fragment thereof that binds to and/or inhibits influenza virus comprising: a heavy chain amino acid sequence comprising HCVR comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO: 21, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 22, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 23 and a light chain amino acid sequence comprising a LCVR comprising a LCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 25, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) a third antibody or antigen-binding fragment thereof that binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades comprising: a heavy chain amino acid sequence comprising a HCVR comprising: a heavy chain amino acid sequence comprising a HCVR comprising: a HCDR1 comprising the amino acid sequence of SEQ ID NO:241, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 242, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 243 and a light chain amino acid sequence comprising a LCVR comprising: a LCDR1 comprising the amino acid sequence of SEQ ID NO: 244, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 245, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 246.

2 . The pharmaceutical composition of claim 1 , wherein each antibody or antigen-binding fragment thereof is formulated in a dosage for administration of 1 mg/kg or less.

3 . The pharmaceutical composition of claim 1 , wherein each antibody or antigen-binding fragment thereof is formulated in a dosage for administration of 0.5 mg/kg or less.

4 . The pharmaceutical composition of claim 1 , wherein each antibody or antigen-binding fragment thereof is formulated in a dosage for administration of 0.1 mg/kg or less.

5 . The pharmaceutical composition of claim 1 , wherein said first antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR)/light chain variable region (HCVR/LCVR) sequence pair of SEQ ID NOs: 19 and 20, said second antibody or antigen-binding fragment thereof comprises an HCVR/LCVR sequence pair of SEQ ID NOs: 29 and 30 and said third antibody or antigen-binding fragment thereof comprises a HCVR/LCVR pair of SEQ ID NOs.: 249-250.

6 . The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is formulated for delivery with a nebulizer.

7 . The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is formulated for delivery with a device selected from a metered dose inhaler, a metered spray pump, a hand-bulb atomizer, a small or large volume nebulizer, an ultrasonic nebulizer and/or a dry powder inhaler.

8 . The pharmaceutical composition of claim 1 , wherein said first antibody is TRL053/Mab53 comprising heavy chain (HC)/light chain (LC) amino acid sequences of SEQ ID NOs: 17 and 18, said second antibody is antibody TRL579/Mab579 comprising a HC/LC amino acid sequences of SEQ ID NOs: 27 and 28, and said third antibody is TRL849 comprising HC/LC amino acid sequences of SEQ ID NOs: 247 and 248.

9 . The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition further comprises a pharmaceutically acceptable carrier, said pharmaceutically acceptable carrier comprising a diluent and/or excipient for nasal or pulmonary delivery and/or

wherein the pharmaceutical composition further comprises an immunological mediator and/or stimulator of the immune response.

10 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises one or more of an antiviral therapeutic, viral replication inhibitor, protease inhibitor, polymerase inhibitor, hemagglutinin inhibitor, bronchodilator, immune modulator, or inhaled corticosteroid.

11 . The pharmaceutical composition of claim 1 , wherein one or more of said antibodies or antigen binding fragments thereof is an antibody fragment selected from Fab, Fab′, and F(ab′)2, scFv, and/or dAb.

12 . A method for the treatment or prophylaxis of influenza infection in a subject which method comprises administering intranasally (IN) or via inhalation to a subject a pharmaceutical composition comprising:

(a) a first antibody or antigen-binding fragment thereof that binds to and/or inhibits influenza virus comprising: a heavy chain amino acid sequence comprising a heavy chain variable region (HCVR) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 11, a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 12 and a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:13 and a light chain amino acid sequence comprising a light chain variable region (LCVR) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 14, a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO: 15, and a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO: 16;

(b) a second antibody or antigen-binding fragment thereof that binds to and/or inhibits influenza virus comprising: a heavy chain amino acid sequence comprising HCVR comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO: 21, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 22, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 23 and a light chain amino acid sequence comprising a LCVR comprising a LCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 25, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 26; and

(c) a third antibody or antigen-binding fragment thereof that binds to one or more strains of each of influenza B Yamagata and influenza B Victoria clades comprising: a heavy chain amino acid sequence comprising a HCVR comprising: a heavy chain amino acid sequence comprising a HCVR comprising: a HCDR1 comprising the amino acid sequence of SEQ ID NO:241, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 242, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 243 and a light chain amino acid sequence comprising a LCVR comprising: a LCDR1 comprising the amino acid sequence of SEQ ID NO: 244, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 245, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 246.

13 . The method of claim 12 , wherein each antibody or antigen-binding fragment thereof of the pharmaceutical composition is formulated in a dosage for administration of 1 mg/kg or less.

14 . The method of claim 12 , wherein each antibody or antigen-binding fragment thereof of the pharmaceutical composition is formulated in a dosage for administration of 0.5 mg/kg or less.

15 . The method of claim 12 , wherein each antibody or antigen-binding fragment thereof of the pharmaceutical composition is formulated in a dosage for administration of 0.1 mg/kg or less.

16 . The method of claim 12 , wherein the pharmaceutical composition is administered in a time period selected from the group consisting of (i) up to 24 hours post infection; (ii) up to 48 hours post infection and (iii) up to 72 hours post infection.

17 . The method of claim 12 , wherein the pharmaceutical composition is administered in one or more doses before infection or exposure to virus.

18 . The method of claim 12 , wherein the pharmaceutical composition is administered intranasally or via inhalation in multiple doses of less than 1 mg/kg per dose, wherein the multiple doses are administered at least 2 hours apart and first administered up to 72 hours after presumed infection or exposure to virus.

19 . The method of claim 12 , wherein the method further comprises administering intraperitoneally (IP) or intravenously (IV) at least one virus specific monoclonal antibody,

wherein the additionally administered virus specific monoclonal antibody is a neutralizing or non-neutralizing antibody and is the same as or is different from at least one of the antibodies or antigen-binding fragments of the intranasally or via inhalation administered pharmaceutical composition.

20 . The method of claim 19 , wherein the additionally administered virus specific monoclonal antibody is a non-neutralizing virus specific monoclonal antibody.

21 . The method of claim 19 , wherein the additionally administered virus specific monoclonal antibody is at a dosage of at least 5 mg/kg and each of the antibodies or antigen-binding fragments of the intranasally or via inhalation administered pharmaceutical composition are administered at a dosage of 1 mg/kg or less.

22 . The method of claim 19 , wherein the pharmaceutical composition is administered via a nebulizer.

23 . The method of claim 19 , wherein the pharmaceutical composition is administered via a device selected from a metered dose inhaler, a metered spray pump, a hand-bulb atomizer, a small or large volume nebulizer, an ultrasonic nebulizer and/or a dry powder inhaler.

Assignments (3)
CHANGE OF NAME Recorded Aug 13, 2025
From: TRELLIS BIOSCIENCE, LLC
To: TRELLIS BIOSCIENCE, INC.
Reel/Frame 072444/0890 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2021
From: VIGIL, ADAM; WITTEKIND, MICHAEL
To: CONTRAFECT CORPORATION
Reel/Frame 058471/0217 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2021
From: ESTELLES, ANGELES; KAUVAR, LAWRENCE M.
To: TRELLIS BIOSCIENCE, LLC
Reel/Frame 058471/0288 →
Continuity (5)
Continuation 16674149 · Nov 5, 2019
Division 15116106
Provisional Application 62051630 · Sep 17, 2014
Provisional Application 61935746 · Feb 4, 2014
Related Publication 20220111049A1 · Apr 14, 2022
References Cited (132)
US 4625015A · Green et al. · 1986 [cited by applicant]
US 6235708B1 · Holloway et al. · 2001 [cited by applicant]
US 7262270B2 · Weissenhorn et al. · 2007 [cited by applicant]
US 7696330B2 · Meulen et al. · 2010 [cited by applicant]
US 8192927B2 · Van Den Brink et al. · 2012 [cited by applicant]
US 8288090B2 · Fomsgaard · 2012 [cited by applicant]
US 20030100096A1 · Holloway · 2003 [cited by applicant]
US 20090092620A1 · Moste et al. · 2009 [cited by applicant]
US 20090203538A1 · Sugioka et al. · 2009 [cited by applicant]
US 20090311183A1 · Devy et al. · 2009 [cited by applicant]
US 20090311265A1 · Van Den Brink et al. · 2009 [cited by applicant]
US 20100086555A1 · Lanzavecchia · 2010 [cited by applicant]
US 20110027270A1 · Garcia-Sastre et al. · 2011 [cited by applicant]
US 20110319600A1 · Kuta et al. · 2011 [cited by applicant]
US 20120020971A1 · Kauvar et al. · 2012 [cited by applicant]
US 20120039899A1 · Olsen et al. · 2012 [cited by applicant]
US 20120128671A1 · Horowitz et al. · 2012 [cited by applicant]
US 20160083456A1 · Wittekind et al. · 2016 [cited by applicant]
JP 62175426A · 1987 [cited by applicant]
JP 2005519586A · 2005 [cited by applicant]
JP 2013531993A · 2013 [cited by applicant]
JP 2013539357A · 2013 [cited by applicant]
SU 745523A1 · 1980 [cited by applicant]
WO 2004080403A2 · 2004 [cited by applicant]
WO 2007134327A2 · 2007 [cited by applicant]
WO 2008028946A2 · 2008 [cited by applicant]
WO 2008110937A2 · 2008 [cited by applicant]
WO 2009053604A2 · 2009 [cited by applicant]
WO 2009079259A2 · 2009 [cited by applicant]
WO 2009121004A2 · 2009 [cited by applicant]
WO 2010010466A2 · 2010 [cited by applicant]
WO 2010010467A2 · 2010 [cited by applicant]
WO 2010022120A1 · 2010 [cited by applicant]
WO 2010027818A2 · 2010 [cited by applicant]
WO 2010074656A1 · 2010 [cited by applicant]
WO 2010130636A1 · 2010 [cited by applicant]
WO 2011117848A1 · 2011 [cited by applicant]
WO 2011126370A1 · 2011 [cited by applicant]
WO 2011160083 · 2011 [cited by applicant]
WO 2012045001A2 · 2012 [cited by applicant]
WO 2013007770A1 · 2013 [cited by applicant]
WO 2013086052 · 2013 [cited by applicant]
WO 2013114885A1 · 2013 [cited by applicant]
WO 2013132007A1 · 2013 [cited by applicant]
WO 2014152841A1 · 2014 [cited by applicant]
Ison MG. Antivirals and resistance: influenza virus. Curr Opin Virol. 2011;1(6):563-573 (Year: 2011). [cited by examiner]
Office Action issued in corresponding Mexican Patent Application No. MX/a/2016/010059 dated Nov. 1, 2021 and partial English language translation (11 pages). [cited by applicant]
Damschroder, M. et al. “Framework shuffling of antibodies to reduce immunogenicity and manipulate functional and biophysical properties”, Molecular Immunology, 2007, vol. 44, pp. 3049-3060. [cited by applicant]
Mcconnell, A. et al. “An integrated approach to extreme thermostabilization and affinity maturation of an antibody”, Protein Engineering, Design & Selection, 2013, vol. 26, No. 2, pp. 151-163. [cited by applicant]
Canadian Office Action issued in corresponding Canadian Patent Application No. 2,938,726 dated Nov. 29, 2021 (4 pages). [cited by applicant]
Min Dai et al, “Long-lasting Complete Regression of Established Mouse Tumors by Counteracting Th2 Inflammation”, Journal of Immunotherapy, (May 1, 2013), vol. 36, No. 4, pp. 248-257. [cited by applicant]
Altshuler, E.P. et al, Generation of Recombinant Antibodies and Means for Increasing Their Affinity, Biochemistry, 2010, vol. 50, pp. 203-258. [cited by applicant]
Ehrenmann, F. et al, IMGT/3Dstructure-DB and IMGT/DomainGapAlign: a database and a tool for Immunoglobulins or antibodies, T cell receptors, MHC, IgSF and MhcSF, Nucleic Acids Research, 2010, vol. 38, pp. D301-D307. [cited by applicant]
Feng, J. et al, Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy chain isotype, Journal of Virology, 20… [cited by applicant]
Friesen et al, New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets, PLoS One, 2010, vol. 5, No. 2, p. EL906. [cited by applicant]
Huber V.C. et al, Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections, Journal of Immunology, 2001, vol. 166, pp. 7381-7738. [cited by applicant]
Jegerlehner, A. et al, Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity, Journal of Immunology, 2004, vol. 172, pp. 5598-5605. [cited by applicant]
Mozdzanowska, K. et al, Enhancement of neutralizing activity of influenza virus-specific antibodies by serum components, Virology, 2006, vol. 352, pp. 418-426. [cited by applicant]
Newsome, B.W. et al, The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have magic bullets arrived?, The Journal of Clinical Pharmacology, 2008, vol. 66, No. 1, pp. 6-19. [cited by applicant]
Tan, G.S. et al, A Pan-H1 Anti-Hemagglutinin Monoclonal Antibody with Potent Broad Spectrum Efficacy In Vivo, Journal of Virology, 2012, vol. 86, No. 11, pp. 6179-6188. [cited by applicant]
Communication from the European Patent Office issued in European Patent Application No. 15 704 447 on Jun. 21, 2018, pp. 1-10. [cited by applicant]
Communication from the European Patent Office issued in European Patent Application No. 15 704 447 on Feb. 21, 2018, pp. 1-6. [cited by applicant]
English-language translation of Japanese Office Action issued in Japanese Patent Application No.2016-550714 on Jan. 15, 2019, pp. 1-7. [cited by applicant]
English-language translation of Japanese Office Action issued in Japanese Patent Application No.2016-550714 on Oct. 8, 2019, pp. 1-9. [cited by applicant]
English-language translation of Russian Office Action issued in Russian Patent Application No. 2016132419/10(050278) on Oct. 31, 2018, pp. 1-3. [cited by applicant]
Australian Office Action issued in Australian Patent Application No. 2015214146 on Sep. 3, 2019, pp. 1-6. [cited by applicant]
Murphy, M., Office Action issued in corresponding Canadian Patent Application No. 2,938,726 dated Jan. 19, 2021 (4 pages). [cited by applicant]
Saku, T., Office Action issued in corresponding Japanese Patent Application No. 2020-019359 dated Apr. 6, 2021 (11 pages). [cited by applicant]
Office Action issued in corresponding Israel Patent Application No. 268431 dated Aug. 31, 2021 and partial English language translation (5 pages). [cited by applicant]
Office Action issued in corresponding Japanese Patent Application No. 2020-019359 dated Sep. 22, 2021 and English language translation (4 pages). [cited by applicant]
Russian Patent Office Action issued in corresponding Russian patent application No. 2016132419 on Jul. 8, 2019, pp. 1-3, with English translation. [cited by applicant]
Yarilin, A. A., “Fundamentals of Immunology,” Meditsyna (1999) Moscow, pp. 172-174, with English translation. [cited by applicant]
Israeli Office Action issued in corresponding Israeli patent application No. 247075, dated Apr. 7, 2019, pp. 1-6. [cited by applicant]
Clementi, N., et al., “Broad-range neutralizing anti-influenza A human monoclonal antibodies: new perspectives in therapy and prophylaxis,” New Microbiologica, 2012, vol. 35, pp. 399-406. [cited by applicant]
Kalenik, B., et al. “Influenza prevention and treatment by passive immunization,” Acta Biochimica Polonica, 2014, vol. 61, No. 3, pp. 573-587. [cited by applicant]
Rudikoff, S. et al., “Single amino acid substitution altering antigen-binding specificity,” Proc. Natl. Acad. Sci. USA, 1982, vol. 79, pp. 1979-1983. [cited by applicant]
Baker et al., Protein Structure Predication and Structural Genomics, Science, 2001, vol. 294, No. 5540, pp. 93-96. [cited by applicant]
Attwood, T., The Babel of Bioinformatics, Science, 2000, vol. 290, No. 5491, pp. 471-473. [cited by applicant]
Abrahamson, M. et al., “Identification of the Probable Inhibitory Reactive Sites of the Cysteine Proteinase Inhibitors Human Cystatin C and Chicken Cystatin,” The Journal of Biological Chemistry, 1987, vol. 262, No. 20,… [cited by applicant]
Bianchi et al., “Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor.” J Virol (2005) 79(12): 7380-7388. [cited by applicant]
Bright et al., “Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle.” PLoS One (Jan. 30, 2008), 3(1):e1501. [cited by applicant]
Carragher et al. “A Novel Role for Non-Neutralizing Antibodies against Nucleoprotein in Facilitating Resistance to Influenza Virus.” J Immunol 2008; 181 :4168-4176. [cited by applicant]
Corti et al., “A neutralizing antibody selected from plasma cells that binds to group 1 and D group 2 influenza A hemaaalutinins.” Science (2011) 333(6044): 850-856. [cited by applicant]
Donis et al. “Distinct Lineages of Influenza Virus H4 Hemagglutinin Genes in Different Regions of the World.” Virology (1989) 169:408-417. [cited by applicant]
Doyle et al. “A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug-resistant strains,” Biochemical and Biophysical Res. Communications, vol. 441, No. 1… [cited by applicant]
Dreyfus, et al., “Highly conserved protective epitopes on influenza B viruses,” 22, Science, vol. 337, No. 6100, Sep. 14, 2012, pp. 1343-1348. XP002693350, American Association for the Advancement of Science, US ISSN: 1… [cited by applicant]
Ekiertet al. “A highly conserved neutralizing epitope on group 2 influenza A viruses.” Science (2011) 333 (6044): 843-850. [cited by applicant]
Ekiert et al. “Antibody Recognition of a Highly Conserved Influenza Virus Epitope.” Science (2009) 324: 246-251. [cited by applicant]
Grandea et al., “Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses,” Proc. Natl. Acad. Sci. USA (2010), vol. 107, No. 28, pp. 12658-12663. [cited by applicant]
International Preliminary Report on Patentability and Written Opinion for International Patent Application No. PCT/US2012/068037, issued Jun. 10, 2014, 14 pages. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2015/014521 mailed Aug. 11, 2015, 17 pages. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2012/068037, mailed Jun. 12, 2013, 14 pages. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2011/040982, mailed Nov. 25, 2011, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2014/027939, mailed Aug. 28, 2014, 14 pages. [cited by applicant]
Kostolansky et al., “Antibody Response to Hidden Epitope of Influenza A Haemagglutinin Elicited by Anti-Idiotypic Antibodies,” Acta vifologica (1994) 38:215-222. [cited by applicant]
Krause et al., “A Broadly Neutralizing Human Monoclonal Antibody That Recognizes a Conserved, Novel Epitope on the Globular Head of the Influenza H1N1 Virus Hemagglutinin,” Journal of Virology, vol. 85, No. 20, Oct. 15,… [cited by applicant]
Kuboto-Koketsu et al., “Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors.” Biochem Biophys Res Commun (Sep. 11, 2009), 387(1): 180-5. [cited by applicant]
Mccutcheon et al. “Multiplexed screening of natural humeral immunity identifies antibodies at fine specificity for oomplex and dynamic viral targets”, MABS (Jan. 8, 2014), 6(2):460-473. [cited by applicant]
Mottet et al. “Characterization of Sendai virus M protein mutants that can partially interfere with virus particle productionm” Journal of Virology, 1999, vol. 80, pp. 2977-2986. [cited by applicant]
Prabhu et al., “Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N 1 Infection,” Journal of Virology (2009) 83(6):2553-2562. [cited by applicant]
Schoofs et al., “Epitopes of an influenza viral peptide recognized by antibody at single amino acid resolution,” Journal of Immunology, 1988, vol. 140 pp. 611-616. [cited by applicant]
Song, G. et al.,“Progesterone and Interferon Regulate Cystatin C in the Endometrium,” Endocrinology, 2006, vol. 147, pp. 3478-3483. [cited by applicant]
Steel et al. “Influenza virus vaccine based on the conserved hemagglutinin stalk domain,” Mbio (Apr. 2010), 1(1): 1-9. [cited by applicant]
Sui et al., “Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses,” Nat Struct Mol Biol (2009) 16(3):265-273. [cited by applicant]
Sui et al. “Wide Prevalence of Heterosubtypic Broadly Neutralizing Human Anti-Influenza A Antibodies,” Clinical Infectious Diseases (Apr. 15, 2011), 52(8):1003-1009. [cited by applicant]
Supplementary European Search Report for European Patent Application No. 12854682.7, issued Aug. 7, 2015, 8 pages. [cited by applicant]
Supplementary European Search Report for European Patent Application No. EP 11796555.8, issued Oct. 22, 2013, 17 pages. [cited by applicant]
Throsby et al., “Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1 N1 recovered from human IgM+ memory B cells,” PLoS One (2008) 3(12):e3942. [cited by applicant]
Usinger et al., “Human monoclonal antibody 53 shows unique cross-clade neutralization of influenza,” American Society of Virology (Jul. 16-20, 2011), Abstract only. [cited by applicant]
Wagner et al, “Bispecific antibody generated with sortase and click chemistry has broad antiinfluenza virus activity,” Proceedings of the National Academy of Sciences (Nov. 10, 2014), 111 (47):16820-16825. [cited by applicant]
Wang et al., “Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization With Different Hemagglutinins.” PLoS (Feb. 2010), 6(2):e1000796. [cited by applicant]
Weltzin et al., “Intranasal Antibody Prophylaxis for Protection Against Viral Disease.” Clinical Microbiology Reviews, Washington, D.C., US, vol. 12, No. 3, Jul. 1, 1999 (Jul. 1, 1999), pp. 383-393. [cited by applicant]
Yasugi et al. “Human monoclonal antibodies broadly neutralizing against influenza B virus.” PLoS Pathogens (Feb. 2013), 9(2):1-12. [cited by applicant]
Ye et al., “Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice,” Clinical and Vaccine Immunology, Sep. 2010, pp. 1363-1370. [cited by applicant]
Yoshida et al., “Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutinin of influenza A viruses,” PLoS Pathog (2009) 5(3):e1000350. [cited by applicant]
Zanin et al., “An Anti-H5N1 Influenza Virus FcDart Antibody is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection,” Journal of Virology (Feb. 11, 2015), 89(8):4549-4561. [cited by applicant]
Ziegler et al., “Type- and Subtype-Specific Detection of Influenza Viruses in Clinical Specimens by Rapid Culture Assay,” Journal of Clinical Microbiology (1995) 33(2):318-321. [cited by applicant]
Indian Office Action issued in corresponding Indian Application No. 201627030111 on Dec. 11, 2019, pp. 1-8. [cited by applicant]
European Office Action issued in corresponding European Application No. 15 704 447.0 on Dec. 19, 2019, pp. 1-6. [cited by applicant]
Chinese Office Action issued in corresponding Chinese Application No. 201580018794.7 on Dec. 25, 2019, pp. 1-11, with English translation. [cited by applicant]
Hie et al., Effective intranasal therapeutics and prophylactics with monoclonal anitbody against lethal infection of H7N7 influenza virus, Antiviral Research, vol. 100, 2013, pp. 207-214. [cited by applicant]
Hernandez et al., Compared Protective Effect of Nasal Immunoprophylaxis Using a New Human Monoclonal IgM Antibody, Human Polyclonal Antibodies, F(ab′)2, Amantadine, and Zanamivir for Prophylaxis of Influenza A Virus Pne… [cited by applicant]
Gronvik et al., Prophylactic treatment with IgY antibodies against influenza viruses does not interfere with the normal development of adaptive immunological memory against influenza, Immunology, vol. 137 (suppl. 1), 20… [cited by applicant]
Office Action issued in corresponding Mexican Patent Application No. MX/a/2016/010059 on Apr. 13, 2021, 14 pages (with English language translation). [cited by applicant]
Office Action issued in corresponding Israel Patent Application No. 268431 dated May 21, 2020 and partial English language translation (5 pages). [cited by applicant]
Office Action issued in corresponding Mexican Patent Application No. MX/a/2016/010059 dated Jul. 16, 2020 and partial English language translation (9 pages). [cited by applicant]
Office Action issued in corresponding Chinese Patent Application No. 201580018794.7 dated Jul. 23, 2020 and English language translation (18 pages). [cited by applicant]
Office Action issued in corresponding Brazilian Patent Application No. 112016018082-8 dated Oct. 20, 2020 and English language translation (6 pages). [cited by applicant]
Yasugi et al., “Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus” PLOS Pathogens, 2013, vol. 9, No. 2: e1003150. https://doi.org/10.1371/journal.ppat.1003150, pp. 1-11. [cited by applicant]
Min Dai et al., “Long-lasting Complete Regression of Established Mouse Tumors by Counteracting Th2 Inflammation”, Journal of Immunotherapy, 2013, vol. 36, No. 4, doi:10.1097/CJI.0b013e3182943549, pp. 248-257. [cited by applicant]
Wei et al., “Combinatorial PD-1 Blockade and CD137 Activation Has Therapeutic Efficacy in Murine Cancer Models and Synergizes with Cisplatin”, PLOS ONE, 2013, vol. 8, No. 12, doi:10.1371/journal. pone.0084927, p. e84927… [cited by applicant]
J. Duraiswamy et al., “Therapeutic PD-1 Pathway Blockade Augments with Other Modalities of Immunotherapy T-Cell Function to Prevent Immune Decline in Ovarian Cancer”, Cancer Research, 2013, vol. 73, No. 23, 6900-6912, d… [cited by applicant]