IP Library › Granted Patent US 12,551,512
Granted Patent B2
US 12,551,512 · App. 17/764,127 · Granted Feb 17, 2026

Therapeutic efficacy by pulmonary delivery of live attenuated mycobacteria

Inventors: Juan Ignacio Aguiló (Saragossa, ES); Carlos Martín Montañes (Saragossa, ES); Raquel Tarancón Íñiguez (Saragossa, ES); Elena Mata Lozano (Saragossa, ES); Santiago Uranga Maíz (Saragossa, ES); Dessislava Vaneva Marinova (Saragossa, ES)
Assignee: UNIVERSIDAD DE ZARAGOZA
A61K35/74A61P11/06A61P31/06A61P37/08A61K2039/522A61K2039/544A61K2039/577A61K2039/58
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Quick Facts
Patent No.
US 12,551,512
App. No.
17/764,127
Granted
Feb 17, 2026
Kind
B2
Abstract

The present invention is directed to a live-attenuated Mycobacterium tuberculosis composition comprising an isolated microorganism belonging to a M. tuberculosis MTBVAC strain having a i) PhoP-phenotype by the inactivation by a genetic deletion of the Rv0757 gene, wherein the open-reading frame (ORF) sequence of phoP consists of SEQ ID NO 4, and ii) the deletion of a second gene, Rv2930 (fadD26), that prevents PDIM production (PDIM-phenotype), wherein the open-reading frame (ORF) sequence of fadD26 consists of SEQ ID NO 2, for use in therapy in a human subject in need thereof, wherein the composition is administered to said subject via pulmonary delivery.

Claims (17)

1 . A method for therapy in a human subject in need thereof, comprising administering a composition to the subject through a pulmonary route by oral inhalation using an aerosol technique, wherein the composition comprises a live-attenuated M. tuberculosis comprising an isolated microorganism belonging to a M. tuberculosis MTBVAC strain having: i) a PhoP− phenotype by inactivation by genetic deletion of the Rv0757 gene, wherein the open-reading frame (ORF) sequence of phoP consists of SEQ ID NO:4, and ii) a deletion of a second gene, Rv2930 (fadD26), that prevents PDIM production, wherein the open-reading frame (ORF) sequence of fadD26 consists of SEQ ID NO:2;

wherein the composition is administered at a dose of at least 10 6 CFUs; and

wherein the method is a prophylactic method, and the subject is at risk of suffering from allergic asthma, or at risk of developing allergic asthma.

2 . The method according to claim 1 , wherein the composition is a lyophilized composition which optionally further comprises stabilizers, bulking agents, or buffers.

3 . The method according to claim 1 , wherein the subject is at risk of infection with M. tuberculosis or at risk of developing tuberculosis disease, or wherein the method is a secondary method and the subject is an infected patient.

4 . The method according to claim 1 , wherein the method further comprises targeting M2 macrophages and alleviating allergic responsiveness in the subject.

5 . The method according to claim 1 , wherein the method is for treatment of allergic asthma in the subject.

6 . The method according to claim 1 , wherein the subject is a neonate at risk of infection with M. tuberculosis or at risk of developing TB disease.

7 . The method according to claim 1 , wherein the method is for treatment of subjects infected with latent and/or active TB, and the subject is selected from neonates and non-neonate humans.

8 . The method of claim 1 , wherein the method is for treating eosinophilic esophagitis (EoE).

9 . The method of claim 6 , wherein the method is for prophylaxis against infections caused by M. tuberculosis.

10 . The method of claim 7 , wherein the non-neonate human is selected from children, adolescents and adults.

11 . A prophylactic method for targeting M2 macrophages to alleviate an allergic response in a human subject in need thereof, comprising administering a composition to the subject through a pulmonary route by oral inhalation using an aerosol technique, wherein the composition comprises a live-attenuated M. tuberculosis comprising an isolated microorganism belonging to a M. tuberculosis MTBVAC strain having: i) a PhoP− phenotype by inactivation by genetic deletion of the Rv0757 gene, wherein the open-reading frame (ORF) sequence of phoP consists of SEQ ID NO:4, and ii) a deletion of a second gene, Rv2930 (fadD26), that prevents PDIM production, wherein the open-reading frame (ORF) sequence of fadD26 consists of SEQ ID NO:2;

wherein the composition is administered at a dose of at least 10 6 CFUs; and

wherein the subject is at risk of suffering from allergic asthma, or at risk of developing allergic asthma.

12 . The method according to claim 11 , wherein the method is for treatment of allergic asthma in the subject.

13 . The method of claim 11 , wherein the method is for treating eosinophilic esophagitis (EoE).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 26, 2022
From: AGUILÓ, JUAN IGNACIO; MARTÍN MONTAÑES, CARLOS; TARANCÓN ÍÑIGUEZ, RAQUEL; MATA LOZANO, ELENA; URANGA MAÍZ, SANTIAGO; VANEVA MARINOVA, DESSISLAVA
To: UNIVERSIDAD DE ZARAGOZA
Reel/Frame 061217/0711 →
Priority Claims (1)
EP 19382827 · Sep 26, 2019 · regional
Continuity (1)
Related Publication 20230263837A1 · Aug 24, 2023
References Cited (49)
US 10673347B2 · Sarnago Andía et al. · 2020 [cited by applicant]
US 11142734B2 · Fernández Ledesma et al. · 2021 [cited by applicant]
US 11224744B2 · Sarnago Andía et al. · 2022 [cited by applicant]
US 20190366365A1 · Santamaría Ramiro et al. · 2019 [cited by applicant]
US 20210340196A1 · Anel Bernal et al. · 2021 [cited by applicant]
WO WO2015126930A2 · 2015 [cited by examiner]
WO 2018006939A1 · 2018 [cited by applicant]
Zhang Y et al. Immunization with an adenovirus-vectored TB vaccine containing Ag85A-Mtb32 effectively alleviates allergic asthma. J Mol Med (Berl). Apr. 2018;96(3-4):249-263. doi: 10.1007/s (Year: 2018) (Year: 2018). [cited by examiner]
Capucilli P, Hill DA. Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications. Clin Rev Allergy Immunol. Aug. 2019;57(1):111-127. doi: 10.1007/s12016-019-08733-0. PMID: 30903437… [cited by examiner]
U.S. Appl. No. 16/971,248, filed Aug. 19, 2020. [cited by applicant]
Arbués Arribas, “Construction and characterization of a new generation of phoP—based vaccines against tuberculosis,” doctoral dissertation, Universidad de Zaragoza, Zaragoza, Spain, 2010. (157 pages). [cited by applicant]
Arbués et al., “Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated [cited by applicant]
Arnoldussen et al., “BCG vaccination and allergy: A systematic review and meta-analysis,” [cited by applicant]
Behr, “BCG—different strains, different vaccines?” [cited by applicant]
Braunstein et al., “Why Wait? The Case for Treating Tuberculosis with Inhaled Drugs,” [cited by applicant]
Camacho et al., “Analysis of the Phthiocerol Dimycocerosate Locus of [cited by applicant]
Camacho et al., “Identification of a virulence gene cluster of [cited by applicant]
Choi et al., “Therapeutic effects of BCG vaccination in adult asthmatic patients: a randomized, controlled trial,” [cited by applicant]
Cole et al., “Deciphering the biology of [cited by applicant]
Cox et al., “Complex lipid determines tissue-specific replication of [cited by applicant]
Díaz et al., “Comparative Metabolomics between [cited by applicant]
Erb et al., “Infection of Mice with [cited by applicant]
Girodet et al., “Alternative Macrophage Activation is Increased in Asthma,” [cited by applicant]
Gonzalo-Asensio et al., “MTBVAC: Attenuating the Human Pathogen of Tuberculosis (TB) Toward a Promising Vaccine against the TB Epidemic,” [cited by applicant]
Guerra-Maupome et al., “Aerosol vaccination with Bacille Calmette-Guerin induces a trained innate immune phenotype in calves,” [cited by applicant]
Holgate, “Innate and adaptive immune responses in asthma,” [cited by applicant]
Holgate et al., “Asthma,” [cited by applicant]
Kwok et al., “Direct ex vivo analysis of allergen-specific CD4 [cited by applicant]
Lagranderie et al., “ [cited by applicant]
Malaga et al., “Production of unmarked mutations in mycobacteria using site-specific recombination,” [cited by applicant]
Marinova et al., “MTBVAC from discovery to clinical trials in tuberculosis-endemic countries,” [cited by applicant]
Mills et al., “M-1/M-2 Macrophages and the Th1/Th2 Paradigm,” [cited by applicant]
Moreira et al., “Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease,” [cited by applicant]
Murray et al., “Protective and pathogenic functions of macrophage subsets,” [cited by applicant]
Obihara et al., “ [cited by applicant]
O'Hehir et al., “T Cell Epitope Peptide Therapy for Allergic Diseases,” [cited by applicant]
Pavord et al., “Mepolizumab for severe eosinophilic asthma (DREAM): a multicenter, double-blind, placebo-controlled trial,” [cited by applicant]
Saradna et al., “Macrophage Polarization and Allergic Asthma,” [cited by applicant]
Sarinho et al., “BCG scar diameter and asthma: A case-control study,” [cited by applicant]
Schrager et al., “Developing aerosol vaccines for [cited by applicant]
Spertini et al., “Safety of human immunization with a live-attenuated [cited by applicant]
Stein et al., “Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children,” [cited by applicant]
Strachan, “Hay fever, hygiene, and household size,” [cited by applicant]
Tameris et al., “Live-attenuated [cited by applicant]
Tarancón et al., “ [cited by applicant]
Trivedi et al., “Dissecting the Mechanism and Assembly of a Complex Virulence Mycobacterial Lipid,” [cited by applicant]
Tsujimura et al., “Effects of Mycobacteria Major Secretion Protein, Ag85B, on Allergic Inflammation in the Lung,” [cited by applicant]
Von Bubnoff et al., “Antigen-presenting cells in allergy,” [cited by applicant]
Von Mutius et al., “International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema,” [cited by applicant]