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61. 发明专利

DE69734110T2 未知
公开(公告)号：DE69734110T2
公开(公告)日：2006-06-29
申请号：DE69734110
申请日：1997-10-30
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA , GIULIANI MONICA , RAPPUOLI RINO
IPC分类号： A01K67/027 , C12N15/31 , A61K38/00 , A61K39/00 , A61K39/108 , A61K39/39 , A61K49/00 , A61P1/12 , A61P31/04 , A61P37/04 , C07K14/245 , C12N1/21 , C12N15/09 , C12Q1/48 , C12R1/19 , G01N33/50
摘要： An immunogenic detoxified protein is provided which comprises the amino acid sequence of subunit A of an E.coli heat labile toxin (LT-A) or a fragment thereof in which at least amino acid Ala-72 of the A subunit is mutated, preferably by substitution with Arg. The toxoid is useful as vaccine against an enterotoxigenic strain of E.coli and is produced by recombinant DNA means by site-directed mutagenesis. It is also an effective adjuvant.

62. 发明专利

CA2584778A1 IMMUNOGENIC BACTERIAL VESICLES WITH OUTER MEMBRANE PROTEINS 未知
公开(公告)号：CA2584778A1
公开(公告)日：2006-05-04
申请号：CA2584778
申请日：2005-10-28
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA , ADU-BOBIE JEANNETTE , GRANDI GUIDO , NORAIS NATHALIE , FERRARI GERMANO
IPC分类号： A61K39/095 , A61K39/108 , C12N9/10 , C12N15/03
摘要： Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and th at can elicit cross-protective antibody responses with higher bactericidal titr es than OMVs prepared by normal production processes. Thus the invention provid es a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includ es peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity of MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium.

63. 发明专利

BR0315228A 未知
公开(公告)号：BR0315228A
公开(公告)日：2006-04-11
申请号：BR0315228
申请日：2003-10-02
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA
IPC分类号： A61K39/095 , A61P31/04 , C07K14/22
摘要： A small number of defined antigens can provide broad protection against meningococcal infection, and the invention provides a composition which, after administration to a subject, is able to induce an antibody response in that subject, wherein the antibody response is bactericidal against two or three of hypervirulent lineages A4, ET 5 and lineage 3 of N.meningitidis serogroup B. Rather than consisting of a single antigen, the composition comprises a mixture of 10 or fewer purified antigens, and should not include complex or undefined mixtures of antigens such as outer membrane vesicles. Five protein antigens are used in particular: (1) a 'NadA' protein; (2) a '741' protein; (3) a '936' protein; (4) a '953' protein; and (5) a '287' protein. Oligomeric 'NadA' is particularly useful.

64. 发明专利

CA2578014A1 DOMAINS AND EPITOPES OF MENINGOCOCCAL PROTEIN NMB1870 未知
公开(公告)号：CA2578014A1
公开(公告)日：2006-03-09
申请号：CA2578014
申请日：2005-09-01
申请人： CHIRON SRL
发明人： GIULIANI MARZIA , PIZZA MARIAGRAZIA , SCARSELLI MARIA , RAPPUOLI RINO , MASIGNANI VEGA , DI MARCELLO FEDERICA , VEGGI DANIELE , CIUCCHI LAURA
IPC分类号： C07K14/22 , A61K39/00 , A61K39/095

65. 发明专利

DE60015084T2 未知
公开(公告)号：DE60015084T2
公开(公告)日：2006-02-16
申请号：DE60015084
申请日：2000-02-09
申请人： CHIRON SRL
发明人： GRANDI GUIDO , RAPPUOLI RINO , GIULIANI MARZIA M , PIZZA MARIAGRAZIA
IPC分类号： A61K39/095 , A61K39/39 , A61P31/04 , C07K14/22 , C12N15/31
摘要： Immunogenic compositions (e.g. vaccines) comprising: (a) an immunostimulating amount of a Neisseria antigen (preferably N. meningitidis serogroup B); and (b) an immunostimulating amount of an adjuvant composition comprising an oligonucleotide comprising at least one CG motif. Component (b) may further comprise a second adjuvant. Component (a) may be selected from a variety of antigens. Adjuvant compositions comprising an oligonucleotide having at least one CG motif, and complete Freund's adjuvant (CFA) are also provided.

66. 发明专利

ES2227762T3 MUTANTES DESTOXIFICADOS INMUNOGENOS DE TOXINA DEL COLERA Y DE LA TOXINA LT,SU PREPARACION Y USO PARA LA PREPARACION DE VACUNAS. 未知
公开(公告)号：ES2227762T3
公开(公告)日：2005-04-01
申请号：ES98200534
申请日：1992-12-30
申请人： CHIRON SRL
发明人： DOMENIGHINI MARIO , RAPPUOLI RINO , PIZZA MARIAGRAZIA , HOL WIM
IPC分类号： A61K38/00 , A61K39/00 , A61K39/106 , A61K39/108 , A61P31/04 , C07K14/195 , C12N15/09 , C07K14/245 , C07K14/28 , C07K14/41 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/31 , C12P21/02
摘要： UNA PROTEINA DESTOXIFICADA E INMUNOGENICA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE LA SUBUNIDAD A DE LA TOXINA DEL COLERA (CT - A) O LA SUBUNIDAD A DE UNA TOXINA LABIL AL CALOR DE ESCHERICHIA COLI (LT - A) O UN FRAGMENTO DE ESTAS EN QUE UNO O MAS AMINOACIDOS EN, O EN LAS POSICIONES CORRESPONDIENTES A VAL 53, SER - 63, VAL - 97, TYR - 104 O PRO - 106 ESTAN SUSTITUIDOS POR OTROS AMINOACIDOS O DELECCIONADOS. EJEMPLOS DE SUSTITUCIONES ESPECIFICAS INCLUYEN VAL - 53 - ASP, VAL - 53 - GLU, VAL - 53 TYR, SER - 63 - LYS, VAL - 97 - LYS, VAL - 97 - TYR, TYR - 104 LYS, TYR - 104 - ASP, TYR - 104 - SER, PRO - 106 - SER. LA PROTEINA DESTOXIFICADAS INMUNOGENICA ES UTIL COMO VACUNA CONTRA VIBRIO CHOLERAE O UNA CEPA ENTEROTOXICOGENICA DE ESCHERICHIA COLI Y ES PRODUCIDA POR SISTEMAS DE DNA RECOMBINANTE MEDIANTE MUTAGENESIS DIRIGIDA.

67. 发明专利

AU2002256859A1 Adp-ribosylating bacterial toxins 未知
公开(公告)号：AU2002256859A1
公开(公告)日：2002-10-15
申请号：AU2002256859
申请日：2002-03-28
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA , RAPPUOLI RINO , MASIGNANI VEGA
IPC分类号： A61K38/00 , A61K39/00 , C07K14/22 , C07K14/255 , C07K14/315 , C07K14/36 , C12N15/31 , A61K39/095 , A61K39/112 , A61K39/02 , C07K14/30
摘要： ADP-ribosylating toxins from Neisseria meningitidis, Streptomyces coelicolor, Mycoplasma pneumoniae, Salmonella typhimurium, Salmonella paratyphi, and Streptococcus pyogenes are disclosed, together with mutant toxins and uses therefor. There is only a low level of sequence identity between these toxins and toxins such as cholera toxin and E. coli heat labile toxin.

68. 发明专利

CA2497279C MUTANT FORMS OF MENINGOCOCCAL ADP-RIBOSYLATING TOXIN 未知
公开(公告)号：CA2497279C
公开(公告)日：2013-02-19
申请号：CA2497279
申请日：2003-09-01
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA , MASIGNANI VEGA
IPC分类号： C12N15/31 , A61K39/00 , A61K39/095 , A61K39/395 , C07K14/22 , C07K16/12
摘要： NMB1343 is an ADP-ribosylating toxin from Neisseria meningitidis. The invention provides a mutant toxin having a substitution at one or more of amino Glu-109, Glu-111 or Glu-120. The mutations(s) is/are preferably Glu to Asp. The protein of the invention preferably has reduced or eliminated ADP-ribosyltransferase and/or NAD-glycohydrolase activity relative to the wild-type protein.

69. 发明专利

BRPI0517514A 未知
公开(公告)号：BRPI0517514A
公开(公告)日：2008-10-14
申请号：BRPI0517514
申请日：2005-10-28
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA , ADU-BOBIE JEANNETTE , NORAIS NATHALIE , FERRARI GERMANO , GRANDI GUIDO
IPC分类号： A61K39/095 , A61K39/108 , C12N9/10 , C12N15/03
摘要： Knockout of the mltA gene gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titres than OMVs prepared by normal production processes. Thus the invention provides a bacterium, such as an E.coli, having a knockout mutation of its mltA gene. The invention also provides a Escherichia bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity of MItA protein. Tol-Pal knockouts of pathogenic E.coli are also disclosed. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium.

70. 发明专利

NZ537976A Hybrid and tandem expression of neisserial proteins 未知
公开(公告)号：NZ537976A
公开(公告)日：2008-03-28
申请号：NZ53797602
申请日：2002-09-06
申请人： CHIRON SRL
发明人： PIZZA MARIAGRAZIA
IPC分类号： C12N15/09 , A61K39/00 , A61K39/08 , A61K39/085 , A61K39/09 , A61K39/095 , A61K39/102 , A61K39/106 , A61K39/118 , A61K39/13 , A61K39/145 , A61K39/165 , A61K39/205 , A61K39/29 , C07H21/00 , C07K14/195 , C07K14/22 , C07K19/00 , C12N15/10 , A61K38/16 , C12N15/62
摘要： Disclosed is a hybrid protein having formula: NH2-A-[-X-L-]n-B-COOH wherein L is an optional linker amino acid sequence, A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, and n is an integer greater than 1, and X is either: (a) an amino acid sequence provided as any one of SEQ ID NOs: 28 and 29; (b) an amino acid sequence having at least 70% sequence identity to any amino acid sequence from (a); or (c) an amino acid sequence comprising a functional fragment of at least 7 amino acids of any amino acid sequence from (a). Also disclosed is a hybrid protein having formula: NH2-A-[-X-L-]n-B-COOH wherein X is an amino acid sequence, L is an optional linker amino acid sequence, A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, and n is an integer greater than 1, and wherein a first X moiety (-Xa-) has one of the following amino acid sequences: (a) an amino acid sequence provided as any one of SEQ ID NOs: 28 and 29; (b) an amino acid sequence having at least 70% sequence identity to any amino acid sequence from (a); or (c) an amino acid sequence comprising a functional fragment of at least 7 amino acids of any amino acid sequence from (a), and a second -X- moiety (-Xb-), wherein -Xb- has one of the following amino acid sequences: (d) SEQ IDs 32-477; (e) SEQ IDs 47 8-522; (f) SEQ IDs 523-2197; (g) SEQ IDs 2198-4357; (h) SEQ IDs 4358-4373; (i) SEQ ID 4374; (j) an amino acid sequence having at least 70% sequence identity to any amino acid sequence from (d) to (g); or (k) an amino acid sequence comprising a functional fragment of at least 7 amino acids of any amino acid sequence from (d) to (g). The proteins can be used in the manufacture of medicaments to treat Neisseria s.p. infections.

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