ES2556770T3 - Expresión híbrida y en tándem de proteínas procedentes de Neisseria - Google Patents

Expresión híbrida y en tándem de proteínas procedentes de Neisseria Download PDF

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ES2556770T3
ES2556770T3 ES10179788.4T ES10179788T ES2556770T3 ES 2556770 T3 ES2556770 T3 ES 2556770T3 ES 10179788 T ES10179788 T ES 10179788T ES 2556770 T3 ES2556770 T3 ES 2556770T3
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patent application
international patent
protein
seq
proteins
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Mariagrazia Pizza
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GlaxoSmithKline Biologicals SA
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    • 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
    • A61K39/02—Bacterial antigens
    • A61K39/095—Neisseria
    • 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
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • 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
    • 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
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/22—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Neisseriaceae (F)
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505—Inorganic adjuvants
    • 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
    • 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

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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Abstract

Una composición que comprende las siguientes proteínas: (1) NH2-A-[X-L-]n-B-COOH, en la que n>= 2, X1>= 287, X2>= 953 (2) 961 (3) NH2-A-[X-L-]n-B-COOH, en la que n>= 2, X1>= 936, X2>= 741, en la que 287 es la SEC ID Nº: 3104 del documento WO99/57280 o una proteína que tiene una identidad de secuencia de un 80 % o más con ella, 953 es la SEC ID Nº: 2918 del documento WO99/57280 o una proteína que tiene una identidad de secuencia de un 80 % o más con ella, 961 es la SEC ID Nº: 940 del documento WO99/57280 o una proteína que tiene una identidad de secuencia de un 80 % o más con ella, 936 es la SEC ID Nº: 2884 del documento WO99/57280 o una proteína que tiene una identidad de secuencia de un 80 % o más con ella, 741 es la SEC ID Nº: 2536 del documento WO99/57280 o una proteína que tiene una identidad de secuencia de un 80 % o más con ella, y en la que cada L es una secuencia de aminoácidos engarzadora opcional, A es una secuencia de aminoácidos N-terminal opcional y B es una secuencia de aminoácidos Cterminal opcional.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
5
10
15
20
25
30
35
contra diversas cepas:
2996(B)
MC58(B) NGH38 394/98(B) H44/76(B) F6124(A) BZ133(C) C11(C)
(1)
32000 16000 130000 16000 32000 8000 16000 8000
(2)
256 131000 128 16000 32000 8000 16000 <4
(3)
32000 8000 - - - 8000 - 32000
mezcla
32000 32000 65000 16000 260000 65000 >65000 8000
(X)
4000 4000 1000 1000 >4000 1000 4000 n.d.
’-’ indica que esta cepa no contiene el gen NadA (X) era una combinación de la proteína 287 con vesículas de membrana externa, para comparar
Considerando los ratones individualmente, la mezcla indujo títulos bactericidas elevados y uniformes:
Nº
1 2 3 4 5 6 7 8 9 10
2996
32768 16384 65536 32768 32768 65536 65536 32768 65536 8192
MC58
65536 32768 65536 65536 65536 18192 65536 32768 132768 65536
394/98
65536 4096 16384 4096 8192 4096 32768 16384 8192 16384
Deleción de dominios -961
961 no está presente en la secuencia del genoma del serogrupo A de N. meningitidis [80], aun cuando las regiones circundantes estén conservadas (> 90 %) entre los serogrupos A y B. Las referencias 10 y 11 desvelan formas polimórficas de 961. Se encontró que el gen estaba presente en el 91 % de las cepas del serogrupo B pertenecientes a los linajes hipervirulentos ET-5, ET-37 y el grupo A4, pero estaba ausente en todas las cepas ensayadas del linaje 3. La mayoría de las cepas del serogrupo C ensayadas fueron positivas aunque no perteneciesen a linajes hipervirulentos. Lo mismo ocurrió con las cepas del serogrupo B con serotipos 2a y 2b. Para el serogrupo A, una cepa perteneciente al subgrupo III fue positiva, mientras que las otras dos cepas pertenecientes al subgrupo IV-1 fueron negativas. 961 estaba ausente en N. gonorrhoeae y en las especies comensales N. lactamica y N. cinerea.
Las figuras 1 y 2 muestran dominios en la proteína 961.
Cuando la región anclada (dominio 9) de la proteína 961 se suprime ("961cL") y se expresa en E. coli, la proteína se exporta al periplasma y se segrega en el sobrenadante del cultivo.
Para investigar esto más, se construyeron mutantes de deleción en la región C-terminal de 961 (961cL-Δaro, 961cLΔcc, 961aL, 961aL-Δ1, 961aL-Δ2, 961aL-Δ3) sobre la base de aspectos estructurales (deleciones de residuos aromáticos en los casos del mutante 961cΔaro, y de las regiones de superenrollamiento para los otros). Se analizaron con respecto a expresión y secreción al periplasma y al sobrenadante del cultivo. En todos estos mutantes de deleción, la proteína se produce en gran cantidad, está presente en la fracción periplásmica y se libera al sobrenadante del cultivo.
Referencias
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10
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11

Claims (1)

  1. imagen1
ES10179788.4T 2001-09-06 2002-09-06 Expresión híbrida y en tándem de proteínas procedentes de Neisseria Expired - Lifetime ES2556770T3 (es)

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GBGB0121591.2A GB0121591D0 (en) 2001-09-06 2001-09-06 Hybrid and tandem expression of neisserial proteins
GB0121591 2001-09-06

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ES2556770T3 true ES2556770T3 (es) 2016-01-20

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ES10179755.3T Expired - Lifetime ES2523365T3 (es) 2001-09-06 2002-09-06 Expresión híbrida y en tandem de proteínas de Neisseria
ES10179788.4T Expired - Lifetime ES2556770T3 (es) 2001-09-06 2002-09-06 Expresión híbrida y en tándem de proteínas procedentes de Neisseria
ES02777592T Expired - Lifetime ES2357503T3 (es) 2001-09-06 2002-09-06 Expresión híbrida y en tandem de proteínas de neisseria.

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US (6) US8980277B2 (es)
EP (4) EP2829549A3 (es)
JP (4) JP4511832B2 (es)
CN (2) CN100390196C (es)
AT (1) ATE496063T1 (es)
AU (2) AU2002339217B2 (es)
BR (1) BR0212363A (es)
CA (1) CA2459816C (es)
CY (2) CY1113218T1 (es)
DE (1) DE60238993D1 (es)
DK (3) DK1423419T3 (es)
ES (3) ES2523365T3 (es)
GB (1) GB0121591D0 (es)
MX (2) MXPA04002216A (es)
NZ (3) NZ537976A (es)
PT (3) PT2360176E (es)
RU (2) RU2475495C2 (es)
WO (1) WO2003020756A2 (es)

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