IP Library › Granted Patent US 12,492,243
Granted Patent B2
US 12,492,243 · App. 16/098,908 · Granted Dec 9, 2025

DNA antibody constructs for use against

Inventors: David Weiner (Merion, PA); Ami Patel (Philadelphia, PA); Jian Yan (Wallingford, PA)
Assignees: The Trustees of the University of Pennsylvania; The Wistar Institute of Anatomy and Biology; Inovio Pharmaceuticals, Inc.
C07K16/1214A61K31/407A61K39/40A61P31/04C07K16/00C07K16/12C07K16/468A61K2039/505A61K2039/53C07K2317/31
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Quick Facts
Patent No.
US 12,492,243
App. No.
16/098,908
Granted
Dec 9, 2025
Kind
B2
Abstract

Disclosed herein are mono and bispecific DNA antibodies (DMAbs) targeting Pseudomonas aeruginosa . Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the DMAbs to the subject. The disclosure also provides a method of preventing and/or treating Pseudomonas aeruginosa infection in a subject using said composition and method of generation.

Claims (15)

1 . A nucleic acid molecule encoding one or more DNA monoclonal antibody (DMAb), wherein the nucleic acid molecule comprises a nucleotide sequence encoding one or more of a variable heavy chain region and a variable light chain region of an anti-PcrV DMAb (DMAb-αPcrV) selected from the group consisting of: a nucleotide sequence encoding an amino acid sequence of SEQ ID NO:6 and a nucleotide sequence of SEQ ID NO:5.

2 . The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a cleavage domain.

3 . The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a signal peptide.

4 . The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding an internal ribosome entry site (IRES) element.

5 . The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a signal peptide selected from the group consisting of SEQ ID NO:24 and SEQ ID NO:25.

6 . The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is a ribonucleic acid molecule.

7 . An expression vector comprising the nucleic acid molecule of claim 1 .

8 . A composition comprising the nucleic acid molecule of claim 1 .

9 . The composition of claim 8 , further comprising a pharmaceutically acceptable excipient.

10 . A method of treating a Pseudomonas aeruginosa infection in a subject, the method comprising administering to the subject the nucleic acid molecule of claim 1 .

11 . The method of claim 10 , further comprising administering an antibiotic agent to the subject.

12 . The method of claim 11 , wherein an antibiotic is administered less than 10 days after administration of the nucleic acid molecule or composition.

13 . A method of treating a Pseudomonas aeruginosa biofilm formation in a subject, the method comprising administering to the subject the nucleic acid molecule of claim 1 .

14 . The method of claim 13 , further comprising administering an antibiotic agent to the subject.

15 . The method of claim 14 , wherein an antibiotic is administered less than 10 days after administration of the nucleic acid molecule or composition.

Continuity (2)
Provisional Application 62332363 · May 5, 2016
Related Publication 20190153076A1 · May 23, 2019
References Cited (59)
US 9403901B2 · Digiandomenico · 2016 [cited by applicant]
US 20150274845A1 · Bruenker · 2015 [cited by applicant]
US 20150284448A1 · Weiner · 2015 [cited by applicant]
AU 2012304313A1 · 2014 [cited by applicant]
CN 101910197B · 2014 [cited by applicant]
EP 2747781B1 · 2017 [cited by applicant]
JP 2014526472 · 2014 [cited by applicant]
JP 2014533249 · 2014 [cited by applicant]
JP 2015504421 · 2015 [cited by applicant]
TW I719938B · 2021 [cited by applicant]
WO WO2013070615A1 · 2013 [cited by examiner]
WO 2014093894A2 · 2014 [cited by applicant]
WO 2015089492A2 · 2015 [cited by applicant]
WO WO2015171504A1 · 2015 [cited by examiner]
WO 2015196011A1 · 2015 [cited by applicant]
Edelman et al. 2001 (Degeneracy and complexity in biological systems; PNAS 98(24): 13763-13768). (Year: 2001). [cited by examiner]
Allison, T. L. “Immunosuppressive Therapy in Transplantation”. Nurs Clin North Am 51, 107-120, (2016). [cited by applicant]
Andre, S. et al. “Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage”. J Virol 72, 1497-1503 (1998). [cited by applicant]
Breidenstein, E. B., de la Fuente-Nunez, C. & Hancock, R. E. “Pseudomonas aeruginosa: all roads lead to resistance”. Trends Microbiol 19, 419-426, (2011). [cited by applicant]
Byrd, M. S. et al. “Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production”. Mol Microbiol 73, 622-63… [cited by applicant]
CDC. “Antibiotic Resistance Threats in the United States”, 2013. (2013). [cited by applicant]
Cemazar, M. et al. “Hyaluronidase and collagenase increase the transfection efficiency of gene electrotransfer in various murine tumors”. Human gene therapy 23, 128-137, (2012). [cited by applicant]
Chan, A. C. & Carter, P. J. “Therapeutic antibodies for autoimmunity and inflammation”. Nat Rev Immunol 10, 301-316, (2010). [cited by applicant]
Collignon, P. C. et al. “World Health Organization Ranking of Antimicrobials According to Their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies to Control Antimicrobial Resistance… [cited by applicant]
Deml, L. et al. “Multiple effects of codon usage optimization on expression and immunogenicity of DNA candidate vaccines encoding the human immunodeficiency virus type 1 Gag protein”. J Virol 75, 10991-11001, (2001). [cited by applicant]
Digiandomenico Antonio et al: “A multifunctional bispecific antibody protects against Pseudomonas aeruginosa”, Science Translational Medicine, vol. 6, No. 262, Nov. 12, 2014 (2014-11-12), pp. 262ra155-1. [cited by applicant]
Digiandomenico, A. et al. “Identification of broadly protective human antibodies to Pseudomonas aeruginosa exopolysaccharide Psl by phenotypic screening”. J Exp Med 209, 1273-1287, (2012). [cited by applicant]
Falagas, M. E. et al. “Toxicity after prolonged (more than four weeks) administration of intravenous colistin”. BMC Infect Dis 5, 1, (2005). [cited by applicant]
Fath, S. et al. “Multiparameter RNA and codon optimization: a standardized tool to assess and enhance autologous mammalian gene expression”. PLoS One 6, e17596, (2011). [cited by applicant]
Ferraro, B. et al. “Clinical applications of DNA vaccines: current progress”. Clin Infect Dis 53, 296-302, (2011). [cited by applicant]
Flingai, S. et al. “Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy”. Sci Rep 5, 12616, (2015). [cited by applicant]
Graf, M., Deml, L. & Wagner, R. “Codon-optimized genes that enable increased heterologous expression in mammalian cells and elicit efficient immune responses in mice after vaccination of naked DNA”. Methods Mol Med 94, … [cited by applicant]
Hauser, A. R. “The type III secretion system of Pseudomonas aeruginosa: infection by injection”. Nat Rev Microbiol 7, 654-665, (2009). [cited by applicant]
Hirao, L. A. et al. “Comparative analysis of immune responses induced by vaccination with SIV antigens by recombinant Ad5 vector or plasmid DNA in rhesus macaques”. Molecular therapy : the journal of the American Societ… [cited by applicant]
Hirsch, E. B. & Tam, V. H. “Impact of multidrug-resistant Pseudomonas aeruginosa infection on patient outcomes”. Expert Rev Pharmacoecon Outcomes Res 10, 441-451, (2010). [cited by applicant]
Jackson, K. D., Starkey, M., Kremer, S., Parsek, M. R. & Wozniak, D. J. “Identification of psl, a locus encoding a potential exopolysaccharide that is essential for Pseudomonas aeruginosa PAO1 biofilm formation”. J Bact… [cited by applicant]
Kim, H. et al. “Gene therapy using plasmid DNA-encoded anti-HER2 antibody for cancers that overexpress HER2” Cancer Gene Ther 23, 341-347, (2016). [cited by applicant]
Lim, L. M. et al. “Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing”. Pharmacotherapy 30, 1279-1291, (2010). [cited by applicant]
Lister, P. D., Wolter, D. J. & Hanson, N. D. “Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms”. Clin Microbiol Rev 22, 582-610, (2009… [cited by applicant]
Matera, M. G., Page, C., Rogliani, P., Calzetta, L. & Cazzola, M. “Therapeutic Monoclonal Antibodies for the Treatment of Chronic Obstructive Pulmonary Disease. Drugs”, (2016). [cited by applicant]
Mishra, M. et al. “Pseudomonas aeruginosa Psl polysaccharide reduces neutrophil phagocytosis and the oxidative response by limiting complement-mediated opsonization”. Cell Microbiol 14, 95-106, (2012). [cited by applicant]
Muthumani, K. et al. “Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus”. J Infect Dis 214, 369-378, (2016). [cited by applicant]
Nelson, A. L., Dhimolea, E. & Reichert, J. M. “Development trends for human monoclonal antibody therapeutics”. Nat Rev Drug Discov 9, 767-774, (2010). [cited by applicant]
O'Neill, J. “Tackling Drug-Resistant Infections Globally: Final Report and Recommendations” (2016). [cited by applicant]
Patel Ami et al: “An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model”, Sep. 21, 2017 (Sep. 21, 2017), Nature Communications, vol. 8, Page(s) Article … [cited by applicant]
Perez, N. et al. “Regulatable systemic production of monoclonal antibodies by in vivo muscle electroporation”. Genet Vaccines Ther 2, 2, (2004). [cited by applicant]
Rice, L. B. “Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no Eskape”. J Infect Dis 197, 1079-1081, (2008). [cited by applicant]
Sardesai, N. Y. & Weiner, D. B. “Electroporation delivery of DNA vaccines: prospects for success”. Curr Opin Immunol 23, 421-429, (2011). [cited by applicant]
Schmaljohn, C. S., Spik, K. W. & Hooper, J. W. “DNA vaccines for HFRS: laboratory and clinical studies”. Virus research 187, 91-96, (2014). [cited by applicant]
Schneider, R., Campbell, M., Nasioulas, G., Felber, B. K. & Pavlakis, G. N. “Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and part… [cited by applicant]
Scott, A. M., Wolchok, J. D. & Old, L. J. “Antibody therapy of cancer”. Nat Rev Cancer 12, 278-287, (2012). [cited by applicant]
Ter Meulen, J. “Monoclonal antibodies in infectious diseases: clinical pipeline in 2011”. Infect Dis Clin North Am 25, 789-802, (2011). [cited by applicant]
Thaden, J. T. et al. “Pseudomonas aeruginosa Bacteremic Patients Exhibit Nonprotective Antibody Titers Against Therapeutic Antibody Targets PcrV and Psl Exopolysaccharide”. J Infect Dis 213, 640-648, (2016). [cited by applicant]
Tjelle, T. E. et al. “Monoclonal antibodies produced by muscle after plasmid injection and electroporation”. Molecular therapy : the journal of the American Society of Gene Therapy 9, 328-336, (2004). [cited by applicant]
Warrener Paul et al: “A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models.”, Aug. 2014 (Aug. 2014), Antimicrobial Agents and Chemotherapy Aug. 2014… [cited by applicant]
Weiner, L. M., Surana, R. & Wang, S. “Monoclonal antibodies: versatile platforms for cancer immunotherapy”. Nat Rev Immunol 10, 317-327, (2010). [cited by applicant]
Williams, J. A. “Vector Design for Improved DNA Vaccine Efficacy, Safety and Production”. Vaccines 1, 225-249, (2013). [cited by applicant]
Zegans, M. E. et al. “Association of Biofilm Formation, Psl Exopolysaccharide Expression, and Clinical Outcomes in Pseudomonas aeruginosa Keratitis: Analysis of Isolates in the Steroids for Corneal Ulcers Trial”. JAMA O… [cited by applicant]
Zumla, A. et al. “Host-directed therapies for infectious diseases: current status, recent progress, and future prospects”. Lancet Infect Dis 16, e47-63, (16)00078-5 (2016). [cited by applicant]