Claims for Patent: 8,163,294

Summary for Patent: 8,163,294

Title:	Growth regulatable recombinant BCG compositions
Abstract:	Immunogenic compositions comprising growth regulatable recombinant attenuated intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens are provided. Exemplary immunogenic compositions include, growth regulatable and growth limited recombinant attenuated intracellular pathogen immunogenic compositions.
Inventor(s):	Horwitz; Marcus A. (Los Angeles, CA), Tullius; Michael V. (Encino, CA)
Assignee:	The Regents of the University of California (Oakland, CA)
Application Number:	12/296,660
Patent Claims:	1. An immunogenic composition comprising: a growth regulatable recombinant Bacille Calmette Guerin (rBCG) expressing at least one Mycobacteria major extracellular protein selected from the group consisting of 12 kDa protein, 14 kDa protein, 16 kDa protein, 23.5 kDa protein, 24 kDa protein, 30 kDa protein, 32A kDa protein, 32B kDa protein, 45 kDa protein, 58 kDa protein, 71 kDa protein, 80 kDa protein, and 110 KD protein, and combinations thereof, wherein at least one of said at least one Mycobacteria major extracellular proteins are expressed on one or more extrachromosomal nucleic acid sequences, wherein said growth regulatable rBCG is selected from the group consisting of an auxotroph wherein pantothenic acid is used to regulate the growth of said auxotroph, and a siderophore mutant wherein the siderophore is mycobactin or exochelin, and wherein said Mycobacteria major extracellular proteins are over-expressed and secreted. 2. The immunogenic composition according to claim 1 wherein each of said at least one Mycobacteria major extracellular proteins are expressed from different extrachromosomal nucleic acid sequences. 3. An immunogenic composition comprising: a growth regulatable recombinant rBCG expressing at least one Mycobacteria major extracellular protein selected from the group consisting of 12 kDa protein, 14 kDa protein, 16 kDa protein, 23.5 kDa protein, 24 kDa protein, 30 kDa protein, 32A kDa protein, 32B kDa protein, 45 kDa protein, 58 kDa protein, 71 kDa protein, 80 kDa protein, and 110 KD protein, and combinations thereof, and wherein at least one of said at least one Mycobacteria major extracellular proteins are integrated into the rBCG genome under the control of a strong promoter and over-expressed, and wherein said growth regulatable rBCG is selected from the group consisting of an auxotroph wherein pantothenic acid is used to regulate the growth of said auxotroph, and a siderophore mutant wherein the siderophore is mycobactin or exochelin. 4. The immunogenic composition according to claim 3 wherein more than one of said at least one Mycobacteria major extracellular proteins are integrated into the rBCG genome under the control of a strong promoter and over-expressed. 5. The immunogenic composition according to claim 1 wherein said major extracellular proteins are non-fusion proteins. 6. The immunogenic composition according to claim 1 wherein said Mycobacteria major extracellular protein is from a Mycobacteria species selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium leprae, and Mycobacterium avium intracellulare. 7. The immunogenic composition according to claim 1 wherein said Mycobacteria major extracellular protein is the 30 kDa protein. 8. The immunogenic composition according to claim 1 further comprising a gene capable of expressing at least one cytokine selected from the group consisting of interferon gamma, interleukin-2, interleukin-12, interleukin-4 receptor, granulocyte macrophage colony stimulating factor, and combinations thereof. 9. An immunogenic composition comprising a growth regulatable recombinant attenuated intracellular pathogen wherein said growth regulatable recombinant attenuated intracellular pathogen expresses at least one major extracellular protein of an intracellular pathogen under the control of a strong promoter such that the major extracellular protein is over-expressed, and wherein said growth regulatable recombinant attenuated intracellular pathogen is an rBCG selected from the group consisting of an auxotroph wherein pantothenic acid is used to regulate the growth of said auxotroph, and a siderophore mutant wherein the siderophore is mycobactin or exochelin. 10. The immunogenic composition of claim 9 wherein said growth regulatable recombinant attenuated intracellular pathogen is of the same species as the intracellular pathogen against which the immunogenic composition is directed. 11. The immunogenic composition of claim 9 wherein said growth regulatable recombinant attenuated intracellular pathogen is of a different species than the intracellular pathogen against which the immunogenic composition is directed. 12. The immunogenic composition of claim 9 wherein said at least one major extracellular protein is from an intracellular pathogen selected from the group consisting of Mycobacterium bovis, M. tuberculosis, M. leprae, M. kansasii, M. avium, Mycobacterium sp., Legionella pneumophila, L. longbeachae, L. bozemanii, Legionella sp., Rickettsia rickettsii, Rickettsia typhi, Rickettsia sp., Ehrlichia chaffeensis, Ehrlichia phagocytophila geno group, Ehrlichia sp., Coxiella burnetii, Leishmania sp., Toxpolasma Trypanosoma cruzi, Chlamydia pneumoniae, Chlamydia s.p, Listeria monocytogenes, Listeria sp., Histoplasma sp., Francisella tularensis, Brucella species, Yersinia pestis, Bacillus anthracis, and Salmonella typhi. 13. An immunogenic composition comprising a growth regulatable siderophore-dependent rBCG wherein said growth regulatable rBCG expresses the kDa Mycobacteria major extracellular protein and interferon gamma, wherein a nucleic acid sequence encoding for said 30 kDa Mycobacteria major extracellular protein is incorporated into the intracellular pathogen's chromosome(s) under a strong promoter such that said 30 kDa Mycobacteria major extracellular protein is over-expressed and wherein mycobactin is used to allow growth of the rBCG in vitro. 14. The immunogenic composition according to claim 3 wherein said major extracellular proteins are non-fusion proteins. 15. The immunogenic composition according to claim 3 wherein said Mycobacteria major extracellular protein is from a Mycobacteria species selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium leprae, and Mycobacterium avium intracellulare. 16. The immunogenic composition according to claim 3 wherein said Mycobacteria major extracellular protein is the 30 kDa protein. 17. The immunogenic composition according to claim 3 further comprising a gene capable of expressing at least one cytokine selected from the group consisting of interferon gamma, interleukin-2, interleukin-12, interleukin-4 receptor, granulocyte macrophage colony stimulating factor, and combinations thereof.

Details for Patent 8,163,294

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Emergent Biodefense Operations Lansing Llc	BIOTHRAX	anthrax vaccine adsorbed	Injection	103821	11/12/1998		2023-10-16