# US 10,370,419 B2 · Tuberculosis vaccine compositions and related methods > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,370,419 B2 - Document ID: US10370419B2 - Status: Granted - Kind: B2 - Application number: 15/533,434 - Filed: 2015-12-09 - Published: 2018-02-08 - Granted: 2019-08-06 - Earliest claimed: 2014-12-09 - Assignees: The Board of Regents of the University of Textas System - Applicants: Board of Regents, the University of Texas System - Inventors: Jianjun Sun - Web page: https://patentgrep.com/patent/US10370419B2 ## CPC - C07K 14/35: from Mycobacteriaceae (F) - A61K 39/04: Mycobacterium, e.g. Mycobacterium tuberculosis - G01N 33/5695: {Mycobacteria} - A61K 2039/522: {avirulent or attenuated} - G01N 2333/35: from Mycobacteriaceae (F) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Compositions and methods directed to ESAT-6 variants which serve as vaccines for the prevention and prophylactic treatment of TB. ## Claims ### Claim 1 A Mycobacterium tuberculosis variants with mutations in the 6-kDal early secreted antigenic target (ESAT-6) protein, wherein the M. tuberculosis exhibits attenuated virulence in a mammal when compared to the M. tuberculosis with wild type ESAT-6, wherein the ESAT-6 protein variant comprises a glutamine to lysine or arginine substitution at the amino acid position corresponding to position 5 (Q5K) or (Q5R) of SEQ 1D NO: 1. ### Claim 2 (depends on 1) The M. tuberculosis of claim 1, wherein the M. tuberculosis is capable of protecting the mammal from challenge by a virulent M. tuberculosis. ### Claim 3 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises 1 or 2 amino acid substitution at an amino acid position selected from amino acid 25 or 26 of SEQ 1D NO: 1. ### Claim 4 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises an isoleucine to threonine substitution at the amino acid corresponding to position 25 (I25T) of SEQ 1D NO: 1. ### Claim 5 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises a histidine to alanine substitution at the amino acid corresponding to position 26 (H26A) of SEQ 1D NO: 1. ### Claim 6 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises a alanine to glutamic acid substitution at the amino acid corresponding to position 17 (A17E) of SEQ 1D NO: 1. ### Claim 7 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises a lysine to threonine substitution at the amino acid corresponding to position 38 (K38T) of SEQ 1D NO: 1. ### Claim 8 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises an asparagine to leucine substitution at the amino acid corresponding to position 67 (N67L) of SEQ 1D NO: 1. ### Claim 9 (depends on 1) The M. tuberculosis of claim 1, wherein the ESAT-6 protein variant further comprises an arginine to glutamine substitution at the amino acid corresponding to position 74 (R74Q) of SEQ 1D NO: 1. ### Claim 10 A mycobacterium in the Mycobacterium tuberculosis complex, genetically engineered to express ESAT-6 protein comprising glutamine to lysine or arginine substitution at an amino acid position corresponding to position 5, (Q5K) or (Q5R) of SEQ 1D NO: 1. ### Claim 11 A mycobacterium ESAT-6 protein comprising glutamine to lysine or arginine substitution at an amino acid position corresponding to position 5 (Q5K) or (Q5R) of SEQ 1D NO: 1. ### Claim 12 (depends on 11) A The mycobacterium ESAT-6 protein of claim 11, further comprising an isoleucine to threonine substitution at the amino acid position corresponding to position 25 (I25T) of SEQ 1D NO: 1. ### Claim 13 (depends on 11) The mycobacterium ESAT-6 protein of claim 11, further comprising a histidine to alanine substitution at the amino acid corresponding to position 26 (H26A) of SEQ 1D NO: 1. ### Claim 14 (depends on 1) A tuberculosis vaccine comprising the M. tuberculosis of claim 1 in a pharmaceutically acceptable excipient. ### Claim 15 (depends on 10) A tuberculosis vaccine comprising the mycobacterium of claim 10 in a pharmaceutically acceptable excipient. ### Claim 16 (depends on 11) A tuberculosis vaccine comprising the mycobacterium ESAT-6 protein of claim 11 in a pharmaceutically acceptable excipient.