CA2045842A1 - Dna capable of site-specific integration into mycobacteria - Google Patents
Dna capable of site-specific integration into mycobacteriaInfo
- Publication number
- CA2045842A1 CA2045842A1 CA002045842A CA2045842A CA2045842A1 CA 2045842 A1 CA2045842 A1 CA 2045842A1 CA 002045842 A CA002045842 A CA 002045842A CA 2045842 A CA2045842 A CA 2045842A CA 2045842 A1 CA2045842 A1 CA 2045842A1
- Authority
- CA
- Canada
- Prior art keywords
- dna
- bcg
- mycobacteria
- tho
- tran
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000010354 integration Effects 0.000 title claims abstract description 16
- 108020004414 DNA Proteins 0.000 claims abstract description 50
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 37
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 21
- 241000186359 Mycobacterium Species 0.000 claims abstract description 15
- 229960005486 vaccine Drugs 0.000 claims abstract description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 11
- 210000000349 chromosome Anatomy 0.000 claims abstract description 10
- 229920001184 polypeptide Polymers 0.000 claims abstract description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 6
- 241001515965 unidentified phage Species 0.000 claims abstract 2
- 239000013612 plasmid Substances 0.000 claims description 12
- 230000010076 replication Effects 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 5
- 108010061833 Integrases Proteins 0.000 claims description 3
- 102100034343 Integrase Human genes 0.000 claims description 2
- 241000588724 Escherichia coli Species 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229940124597 therapeutic agent Drugs 0.000 abstract description 5
- 239000012634 fragment Substances 0.000 description 25
- 150000002500 ions Chemical class 0.000 description 20
- 239000000427 antigen Substances 0.000 description 16
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- 108010058432 Chaperonin 60 Proteins 0.000 description 15
- 102000036639 antigens Human genes 0.000 description 14
- 108091007433 antigens Proteins 0.000 description 14
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- 230000015572 biosynthetic process Effects 0.000 description 11
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- 238000010276 construction Methods 0.000 description 6
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- 239000013598 vector Substances 0.000 description 6
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 5
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 5
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 5
- 208000037062 Polyps Diseases 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 229930027917 kanamycin Natural products 0.000 description 5
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 5
- 229960000318 kanamycin Drugs 0.000 description 5
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- 101150034533 ATIC gene Proteins 0.000 description 3
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- 238000000746 purification Methods 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 101100117177 Coxiella burnetii (strain RSA 493 / Nine Mile phase I) dnaK gene Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000312117 Phago Species 0.000 description 2
- 101710159752 Poly(3-hydroxyalkanoate) polymerase subunit PhaE Proteins 0.000 description 2
- 101710130262 Probable Vpr-like protein Proteins 0.000 description 2
- 101100313003 Rattus norvegicus Tanc1 gene Proteins 0.000 description 2
- 206010043376 Tetanus Diseases 0.000 description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 206010013023 diphtheria Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 101150062334 int gene Proteins 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 235000012976 tarts Nutrition 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 210000001048 venom Anatomy 0.000 description 2
- 231100000611 venom Toxicity 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 108020005075 5S Ribosomal RNA Proteins 0.000 description 1
- ODPOAESBSUKMHD-UHFFFAOYSA-L 6,7-dihydrodipyrido[1,2-b:1',2'-e]pyrazine-5,8-diium;dibromide Chemical compound [Br-].[Br-].C1=CC=[N+]2CC[N+]3=CC=CC=C3C2=C1 ODPOAESBSUKMHD-UHFFFAOYSA-L 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241001233887 Ania Species 0.000 description 1
- 241001244729 Apalis Species 0.000 description 1
- 101001010152 Aplysia californica Probable glutathione transferase Proteins 0.000 description 1
- 101710125089 Bindin Proteins 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 101150105088 Dele1 gene Proteins 0.000 description 1
- 239000005630 Diquat Substances 0.000 description 1
- 101100042648 Drosophila melanogaster sing gene Proteins 0.000 description 1
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 1
- 239000004243 E-number Substances 0.000 description 1
- 235000019227 E-number Nutrition 0.000 description 1
- 102100038075 Eukaryotic translation initiation factor 2D Human genes 0.000 description 1
- 241000950314 Figura Species 0.000 description 1
- 102100022662 Guanylyl cyclase C Human genes 0.000 description 1
- 101710198293 Guanylyl cyclase C Proteins 0.000 description 1
- 101150023414 HSP60 gene Proteins 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 101150002998 LCAT gene Proteins 0.000 description 1
- 229920006063 Lamide® Polymers 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 241000186367 Mycobacterium avium Species 0.000 description 1
- 241001429274 Mycobacterium virus L5 Species 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241000429017 Pectis Species 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
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- 108091081024 Start codon Proteins 0.000 description 1
- 101150076211 TH gene Proteins 0.000 description 1
- 241000023716 Thopha Species 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- 238000013459 approach Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940096118 ella Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000000091 immunopotentiator Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 108010057342 ligatin Proteins 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000003936 merozoite Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001843 polymethylhydrosiloxane Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 210000003046 sporozoite Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BGRJTUBHPOOWDU-UHFFFAOYSA-N sulpiride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-UHFFFAOYSA-N 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- OOLLAFOLCSJHRE-ZHAKMVSLSA-N ulipristal acetate Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(OC(C)=O)C(C)=O)[C@]2(C)C1 OOLLAFOLCSJHRE-ZHAKMVSLSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16211—Human Immunodeficiency Virus, HIV concerning HIV gagpol
- C12N2740/16222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55390790A | 1990-07-16 | 1990-07-16 | |
| US553,907 | 1990-07-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2045842A1 true CA2045842A1 (en) | 1992-01-17 |
Family
ID=24211262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002045842A Abandoned CA2045842A1 (en) | 1990-07-16 | 1991-06-27 | Dna capable of site-specific integration into mycobacteria |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0556182A4 (ja) |
| JP (1) | JPH06501607A (ja) |
| AU (1) | AU8307791A (ja) |
| CA (1) | CA2045842A1 (ja) |
| WO (1) | WO1992001783A1 (ja) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6566121B1 (en) | 1991-06-13 | 2003-05-20 | Albert Einstein College Of Medicine Of Yeshiva University | Insertional mutations in mycobacteria |
| AU2189392A (en) * | 1991-06-13 | 1993-01-12 | Albert Einstein College Of Medicine Of Yeshiva University | Insertional mutations in mycobacteria |
| FR2710845B1 (fr) * | 1993-10-08 | 1996-03-29 | Lafon Labor | Composition destinée à l'immunothérapie d'un cancer sécrétant l'hCG ou des fragments d'hCG. |
| CN1103781C (zh) | 1993-11-23 | 2003-03-26 | 加利福尼亚大学 | 丰富的细胞外产物和其生产与使用方法 |
| US6752993B1 (en) | 1993-11-23 | 2004-06-22 | The Regents Of The University Of California | Abundant extracellular product vaccines and methods for their production and use |
| US7300660B2 (en) | 1993-11-23 | 2007-11-27 | The Regents Of The University Of California | Abundant extracellular products and methods for their production and use |
| US5679515A (en) * | 1994-10-03 | 1997-10-21 | Pathogenesis Corporation | Mycobacterial reporter strains and uses thereof |
| US6013660A (en) * | 1996-10-02 | 2000-01-11 | The Regents Of The University Of California | Externally targeted prophylactic and chemotherapeutic method and agents |
| JP2001518781A (ja) * | 1997-03-28 | 2001-10-16 | サイタクラナル、ファーマスーティクス、インク | マイコバクテリウム組換えワクチン |
| WO2004016280A1 (ja) * | 2002-08-16 | 2004-02-26 | Japan Science And Technology Agency | 組換えｂｃｇワクチン |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE132195T1 (de) * | 1987-03-02 | 1996-01-15 | Whitehead Biomedical Inst | Rekombinant-mykobakterielle impfstoffe |
| US5504005A (en) * | 1987-03-02 | 1996-04-02 | Albert Einstein College Of Medicine Of Yeshiva University | Recombinant mycobacterial vaccine |
-
1991
- 1991-06-27 CA CA002045842A patent/CA2045842A1/en not_active Abandoned
- 1991-07-09 AU AU83077/91A patent/AU8307791A/en not_active Abandoned
- 1991-07-09 JP JP3513065A patent/JPH06501607A/ja active Pending
- 1991-07-09 WO PCT/US1991/004833 patent/WO1992001783A1/en not_active Application Discontinuation
- 1991-07-09 EP EP91914084A patent/EP0556182A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0556182A4 (en) | 1995-03-01 |
| EP0556182A1 (en) | 1993-08-25 |
| AU8307791A (en) | 1992-02-18 |
| WO1992001783A1 (en) | 1992-02-06 |
| JPH06501607A (ja) | 1994-02-24 |
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