IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0876758
(2004-06-28)
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등록번호 |
US-7291343
(2007-11-06)
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발명자
/ 주소 |
- Fattom,Ali Ibrahim
- Sood,Ramesh K.
- Shepherd,Sara E.
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 |
피인용 횟수 :
1 인용 특허 :
30 |
초록
▼
A majority of E. faecalis and E. faecium clinical isolates fall into two groups and three groups, respectively. Distinct antigens are associate with each of the five groups. The Enterococcus antigens are readily obtained from strains of E. faecalis and E. faecium, and can elicit production of prote
A majority of E. faecalis and E. faecium clinical isolates fall into two groups and three groups, respectively. Distinct antigens are associate with each of the five groups. The Enterococcus antigens are readily obtained from strains of E. faecalis and E. faecium, and can elicit production of protective antibodies. Accordingly, the antigens are useful for vaccines which protect against infection by clinically significant (pathogenic) Enterococcus isolates. The antigens and antibodies generated to the antigens are also useful in diagnostic assays.
대표청구항
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What we claim is: 1. A composition comprising (i) an isolated polysaccharide E. faecalis antigen and (ii) an isolated polysaccharide E. faecium antigen, and (iii) a sterile, pharmaceutically-acceptable carrier therefore, wherein: said isolated polysaccharide E. faecalis antigen is different from sa
What we claim is: 1. A composition comprising (i) an isolated polysaccharide E. faecalis antigen and (ii) an isolated polysaccharide E. faecium antigen, and (iii) a sterile, pharmaceutically-acceptable carrier therefore, wherein: said isolated polysaccharide E. faecalis antigen is different from said isolated polysaccharide E. faecium antigen, and said antigens are selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaceharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 2. A composition as claimed in claim 1, wherein each of said antigens further comprises an immunocarrier conjugated to said antigen. 3. A composition as claimed in claim 2, wherein each of said antigens is conjugated to the same immunocarrier. 4. A composition as claimed in claim 3, wherein said immunocarrier is a recombinantly-produced, non-toxic mutant of Pseudomonas aeruginosa exotoxin A. 5. A multivalent vaccine comprising (i) a conjugate of an immunocarrier with an antigen that specifically reacts with antibodies to ATCC 202013, (ii) a conjugate of an immunocarrier with an antigen that specifically reacts with antibodies to ATCC 202014, (iii) a conjugate of an immunocarrier with an antigen that specifically reacts with antibodies to ATCC 202015, (iv) a conjugate of an immunocarrier with an antigen that specifically reacts with antibodies to ATCC 202016, and (v) a conjugate of an immunocarrier with an antigen that specifically reacts with antibodies to ATCC 202017, and (vi) a sterile, pharmaceutically-acceptable carrier therefor. 6. An immunotherapy method comprising administering to a subject an iminunostimulatory amount of a composition comprising (i) an Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215, wherein said antigen is covalently bonded to an immunocarrier, and (ii) a sterile, pharmaceutically-acceptable carrier therefor. 7. An immunotherapy method comprising administering to a subject an immunostimulatory amount of a composition comprising (i) an isolated polysaccharide E. foecalis antigen and (ii) an isolated polysaccharide E. faecium antigen, and (iii) a sterile, pharmaceutically-acceptable carrier therefore, wherein: said isolated polysaccharide E. faecalis antigen is different from said isolated polysaccharide E. faecium antigen; each of said antigens further comprises an immunocarrier conjugated to said antigen; and said antigens are selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 8. A method of preparing an immunotherapeutic agent against Enterococcus infection, comprising the steps of: (A) immunizing subjects with a composition comprising (i) a polysaccharide Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetainido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215, wherein said antigen is covalently bonded to an immunocarrier, and (ii) a sterile, pharmaceutically-acceptable carrier therefor; (B) collecting plasma from said immunized subjects, and (C) harvesting an immune globulin that contains antibodies directed against Enterococcus from said collected plasma. 9. A method of preparing an immunotherapeutic agent against Enterococcus infection, comprising: (A) immunizing subjects with a composition comprising (i) an isolated polysaceharide E. faecalis antigen and (ii) an isolated polysaccharide E. faecium antigen, and (iii) a sterile, pharmaceutically-acceptable carrier therefore, wherein: said isolated polysaccharide E. faecalis antigen is different from said isolated polysaccharide E. faecium antigen; each of said antigens further comprises an immunocarrier conjugated to said antigen, and said antigens are selected from the group consisting of: a polysaceharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215; (B) collecting plasma from said immunized subjects, and (C) harvesting an immune globulin that contains antibodies directed against Enterococcus from said collected plasma. 10. An isolated immune globulin containing antibodies directed against an Enterococcus antigen selected from the group consisting of: a polysaceharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 11. An immune globulin as claimed in claim 10, containing a monoclonal antibody directed against a polysaccharide E. faecalis antigen and a monoclonal antibody directed against a polysaccharide E. faecium antigen. 12. An isolated immune globulin containing antibodies directed against both a polysaceharide E. faecalis antigen and a polysaccharide E. faecium antigen, wherein said polysaccharide E. faecalis antigen is different from said polysaccharide E. faecium antigen, and wherein said antigens are selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 13. An immunotherapy method comprising administering to a subject an immune globulin containing antibodies directed against an Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 14. An immunotherapy method comprising administering to a subject an immune globulin containing antibodies directed against an Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215, wherein said immune globulin contains a monoclonal antibody directed against an E. faecalis polysaccharide antigen and a monoclonal antibody directed against an E. faecium polysaccharide antigen. 15. An isolated antibody to an Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 16. A monoclonal antibody to an isolated Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215. 17. A diagnostic assay for detecting the presence of anti-Enterococcus antibody in a sample, comprising the steps of: mixing (i) an Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaceharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215, with (ii) a sample suspected of containing Enterococcus-specific antibody; and detecting any binding between said antigen and any Enterococcus-specific antibody in said sample. 18. A diagnostic assay as claimed in claim 17, wherein said antigen is immobilized on a solid matrix. 19. A diagnostic assay for detecting the presence of Enterococcus antigen in a sample, comprising the steps of: mixing (i) an isolated antibody to an Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215, with (ii) a sample suspected of containing Enterococcus antigen; and detecting any binding between said antibody and any Enterococcus antigen in said sample. 20. A diagnostic assay as claimed in claim 19, wherein said antibody is immobilized on a solid matrix. 21. A kit for detecting the presence of Enterococcus antigen in a sample, comprising: a monoclonal Enterococcus antibody that specifically binds to one of ATCC 202013, ATCC 202014, ATCC 202015, ATCC 202016, and ATCC 202017, the monoclonal antibody being labeled with a radioisotope label or an enzyme label; and instructions for carrying out a diagnostic assay comprising the steps of mixing said monoclonal Enterococcus antibody with a sample suspected of containing Enterococcus antigen and detecting any binding between said antigen and said antibody in said sample. 22. A kit as claimed in claim 21, wherein the kit further comprises a solid matirix and wherein said antibody is immobilized on a said solid matrix. 23. A diagnostic assay for detecting the presence of anti-Enterococcus antigen in a sample, comprising the steps of: mixing (i) a monoclonal Enterococcus antibody to an isolated Enterococcus antigen selected from the group consisting of: a polysaccharide E. faecalis antigen comprising 2-acetamido-2-deoxy-glucose, rhamnose, glucose, and 2-acetamido-2-deoxy-galactose in a 1:2:2:2 molar ratio as its major sugar groups and that specifically reacts with antibody to ATCC 20213; a polysaccharide E. faecalis antigen comprising a trisaccharide repeat that comprises a 6-deoxy sugar and that does not comprise sugars with N-acetyl or O-acetyl substituents, wherein the antigen further comprises acidic groups and specifically reacts with antibody to ATCC 20214; and a polysaccharide E. faecium antigen comprising 2-acetamido-2-deoxy-galactose and galactose as its major sugar components and that specifically reacts with antibody to ATCC 20215 with (ii) a sample suspected of containing Enterococcus antigen; and detecting any binding between said antibody and any Enterococcus antigen in said sample. 24. A diagnostic assay as claimed in claim 23, wherein said antibody is immobilized on a solid matrix.
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