Title:
IMPROVEMENTS IN OR RELATING TO DIAGNOSIS AND TREATMENT OF BACTERIAL INFECTIONS
Document Type and Number:
WIPO Patent Application WO/1999/061913
Kind Code:
A2
Abstract:
Disclosed is an isolated compound having the structure shown in Figure 2, wherein n is an integer between 3 and 10 (inclusive) and X may be H, OH, alkyl, aryl, amyl, or an amino acid residue (optionally substituted) or a sugar residue (optionally substituted), and wherein R and R?1¿ are hydrophobic hydrocarbon or fatty acid chains (R may be the same as R?1¿ or different), a method of preparing compositions comprising the compound, and a diagnostic method comprising use of the composition.
Inventors:
LAMBERT PETER ANTHONY (GB)
ELLIOTT THOMAS STUART JACKSON (GB)
ELLIOTT THOMAS STUART JACKSON (GB)
Application Number:
PCT/GB1999/001650
Publication Date:
December 02, 1999
Filing Date:
May 26, 1999
Export Citation:
Assignee:
OXOID LTD (GB)
LAMBERT PETER ANTHONY (GB)
ELLIOTT THOMAS STUART JACKSON (GB)
LAMBERT PETER ANTHONY (GB)
ELLIOTT THOMAS STUART JACKSON (GB)
International Classes:
A61K31/70; A61K39/085; C07H3/04; C07K1/00; C07K16/12; C12N1/20; (IPC1-7): G01N33/569
Domestic Patent References:
| WO1997042343A2 | 1997-11-13 |
Other References:
J.J.OLTVOORT ET AL.: "Synthesis of a Lipoteichoic Acid-Carrier Fragment of Staphylococcus aureus." CARBOHYDRATE RESEARCH., vol. 130, 1984, pages 147-163, XP002120748 ELSEVIER SCIENTIFIC PUBLISHING COMPANY. AMSTERDAM., NL ISSN: 0008-6215
W.FISCHER: "Molecular Analysis of Lipid Macroamphiphiles by Hydrophobic Interaction Chromatography Exemplified with Lipotechoic Acids." ANALYTICAL CHEMISTRY, vol. 208, 1993, pages 49-56, XP002120749 cited in the application
H.I.WERGELAND ET AL.: "Antibodies to Staphylococcal Peptidoglycan and its Peptide Epitopes, Techoic Acid, and Lipotechoic Acid in Sera from Blood Donors and Patients with Staphylococcal Infections." JOURNAL OF CLINICAL MICROBIOLOGY, vol. 27, no. 6, June 1989 (1989-06), pages 1286-1291, XP002120750 cited in the application
J.J.OLTVOORT ET AL.: "A Simple Approach to the Synthesis of a Membrane Techoic Acid Fragment of Staphylococcus aureus." RECUEIL, JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY, vol. 101, no. 3, March 1982 (1982-03), pages 87-91, XP002120751
DATABASE WPI Section Ch, Week 198703 Derwent Publications Ltd., London, GB; Class B04, AN 1987-017786 XP002120752 & JP 61 275217 A (YAKULT HONSHA KK), 5 December 1986 (1986-12-05)
W.FISCHER: "Molecular Analysis of Lipid Macroamphiphiles by Hydrophobic Interaction Chromatography Exemplified with Lipotechoic Acids." ANALYTICAL CHEMISTRY, vol. 208, 1993, pages 49-56, XP002120749 cited in the application
H.I.WERGELAND ET AL.: "Antibodies to Staphylococcal Peptidoglycan and its Peptide Epitopes, Techoic Acid, and Lipotechoic Acid in Sera from Blood Donors and Patients with Staphylococcal Infections." JOURNAL OF CLINICAL MICROBIOLOGY, vol. 27, no. 6, June 1989 (1989-06), pages 1286-1291, XP002120750 cited in the application
J.J.OLTVOORT ET AL.: "A Simple Approach to the Synthesis of a Membrane Techoic Acid Fragment of Staphylococcus aureus." RECUEIL, JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY, vol. 101, no. 3, March 1982 (1982-03), pages 87-91, XP002120751
DATABASE WPI Section Ch, Week 198703 Derwent Publications Ltd., London, GB; Class B04, AN 1987-017786 XP002120752 & JP 61 275217 A (YAKULT HONSHA KK), 5 December 1986 (1986-12-05)
Attorney, Agent or Firm:
KEITH W NASH & CO. (90-92 Regent Street Cambridge CB2 1DP, GB)
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Claims:
CLAIMS
| 1. | An isolated compound having the structure shown in Figure 2, wherein n is an integer between 3 and 10 (inclusive) and X may be H, OH, alkyl, aryl, amyl, or an amino acid residue (optionally substituted) or a sugar residue (optionally substituted), and wherein R and R'are hydrophobic hydrocarbon or fatty acid chains (R may be the same as R'or different). |
| 2. | A compound according to claim 1, wherein n = 6. |
| 3. | A compound according to claim 1 or 2, wherein X = H, OH, Dalanyl or Nacetyl glucosamine. |
| 4. | A composition, comprising a compound in substantially pure form having the structure shown in Figure 2, wherein n is an integer between 3 and 10 (inclusive) and X may be H, OH, alkyl, aryl, amyl, or an amino acid residue (optionally substituted) or a sugar residue (optionally substituted), and R and R'are hydrophobic hydrocarbon or fatty acid chains (R may be the same as R', or different). |
| 5. | A composition according to claim 4, comprising an isolated compound in accordance with any one of claims 1 to 3. |
| 6. | A composition according to claim 4 or 5, in the form of a freezedried solid, an aqueous solution, or immobilised on a solid support. |
| 7. | A method of testing for a Gram +ve bacterial infection in a mammalian (typically, human) subject, the method comprising the steps of : obtaining a sample of body fluid from the subject; contacting the sample with a composition comprising a compound having the structure shown in Figure 2, wherein n is an integer between 3 and 10 (inclusive) and X may be H, OH, alkyl, aryl, amyl, or an amino acid residue (optionally substituted) or a sugar residue (optionally substituted), and R and R'are hydrophobic hydrocarbon or fatty acid chains (R may be the same as R', or different); and detecting binding of antibodies (if any) in the sample to the composition. |
| 8. | A method according to claim 7, wherein the sample of body fluid obtained from the subject comprises whole blood, serum, urine or saliva. |
| 9. | A method according to claim 7 or 8, comprising the detection of binding to the composition of IgG antibodies in the sample. |
| 10. | A method according to any one of claims 7,8 or 9, wherein the test method comprises the performance of an enzymelinked immunosorbent assay (ELISA), radioimmunoassay (RIA), or a Western blot. |
| 11. | A method according to any one of claims 7 to 10, for testing for infection caused by Gram +ve cocci. |
| 12. | A method acoording to any one of claims 7 to 11, for testing for infection by a Streptococcus, a Staphylococcus or an Enterococcus. |
| 13. | A method according to any one of claims 7 to 12, for diagnosing the presence of a Gram +ve infection associated with a central venous catheter, a cerebrospinal fluid shunt or a prosthetic device. |
| 14. | A method according to any one of claims 7 to 13, wherein the composition is in accordance with any one of claims 46. |
| 15. | A diagnostic test kit for diagnosing the presence of a Gram +ve infection in a mammalian subject, the kit comprising: a solid support for performing a diagnostic test; and a composition in accordance with any one of claims 46. |
| 16. | A kit according to claim 15, further comprising one or more of the following: labelled antibody; enzyme substrate; control sample; buffer; and instructions for use. |
| 17. | A sterile vaccine composition for use against a Gram +ve infection in a mammalian subject, the vaccine comprising an isolated compound in accordance with any one of claims 1 to 3, or a composition in accordance with any one of claims 4 to 6. |
| 18. | An immunoglobulin molecule or variant thereof having specific binding for a compound in accordance with any one of claims 1 to 3. |
| 19. | A eukaryotic cell producing an immunoglobulin molecule or variant thereof in accordance with claim 18. |
| 20. | A method of making a composition in accordance with any one of claims 4 to 6, the method comprising the steps of : culturing a Gram +ve bacterium in a growth medium so as to cause the bacterium to secrete into the growth medium the compound having the structure shown in Figure 2; separating the growth medium from the bacterial cells; fractionating the growth medium; and isolating that fraction which comprises, in substantially pure form, the compound having the structure shown in Figure 2. |
| 21. | Staphylococcus epidermidis strain CAN 6KIII, deposited under accession number NCIMB 40896. |
| 22. | Staphylococcus epidermidis strain HAR 6KIV, deposited under accession number NCIMB 40945. |
| 23. | Staphylococcus epidermidis strain COS 6KV, deposited under accession number NCIMB 40946. |
| 24. | Staphylococcus epidermidis strain MIL 6LI, deposited under accession number NCIMB 40947. |
| 25. | Staphylococcus epidermidis strain HED 6LI, deposited under accession number NCIMB 40948. |
| 26. | Staphylococcus haemolyticus strain ONE 6KVI, deposited under accession number NCIMB 40949. |
| 27. | Micrococcus kristinae strain MAT 6LII, deposited under accession number NCIMB 40950. |
| 28. | A method according to claim 20, comprising the step of culturing one or more organisms selected from the group consisting of : Staphylococcus epidermidis strain CAN 6KIII; Staphylococcus epidermidis strain HAR 6KIV; Staphylococcus epidennidis strain COS 6KV; Staphylococcus epidermidis strain MIL 6LI; Staphylococcus epidermidis strain HED 6LI; Staphylococcus haemolyticus strain ONE 6KVI; Micrococcus kristinae strain MAT 6LII. |
| 29. | A method of making an immunoglobulin having specific binding for a molecule in accordance with claim 1, the method comprising the steps of : preparing a composition comprising a compound in accordance with any one of claims 13; administering the composition to a mammalian subject; and obtaining from the subject a sample comprising antibodies or antibodyproducing cells. |
| 30. | A method according to claim 29, wherein antibodyproducing cells are isolated from the subject and used to prepare a hybridoma. |
| 31. | A method of obtaining an immunoglobulin or antigenbinding variant thereof having specific binding for a compound in accordance with any one of claims 13, the method comprising the steps of : screening a library of viruses or other particles displacing an immunoglobulin or antigenbinding variant thereof on their surface; and selecting those members of the library which display an immunoglobulin or antigenbinding variant thereof which bind to the compound. |
| 32. | A method of inducing antibodies in a human subject, the method comprising the steps of preparing a physiologically acceptable composition in accordance with claim 4; and administering the composition to the subject. |
| 33. | A vaccine for inducing antibodies in a mammalian subject the vaccine comprising a composition in accordance with claim 4 and a physiologically acceptable excipient, carrier or diluent. |
Description:
t al Applicatlon No INTERNATIONAL SEARCH REPORT PCT/GB99/01650 C.(Contlnuatlon) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A W. FISCHER:"Molecular Analysis of Lipid 1,4 Macroamphiphiles by Hydrophobic Interaction Chromatography Exemplified with Lipotechoic Acids." ANALYTICAL CHEMISTRY, vol. 208,1993, pages 49-56, XP002120749 cited in the application abstract A H. I. WERGELAND ET AL. :"Antibodies to 1,4 Staphylococcal Peptidoglycan and its Peptide Epitopes, Techoic Acid, and Lipotechoic Acid in Sera from Blood Donors and Patients with Staphylococcal Infections." JOURNAL OF CLINICAL MICROBIOLOGY, vol. 27, no. 6, June 1989 (1989-06), pages 1286-1291, XP002120750 cited in the application abstract A J. J. OLTVOORT ET AL.:"A Simple Approach 1,4 to the Synthesis of a Membrane Techoic Acid Fragment of Staphylococcus aureus." RECUEIL, JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY, vol. 101, no. 3, March 1982 (1982-03), pages 87-91, XP002120751 the whole document A DATABASE WPI 1,4 Section Ch, Week 198703 Derwent Publications Ltd., London, GB ; Class B04, AN 1987-017786 XP002120752 &JP 61 275217 A (YAKULT HONSHA KK), 5 December 1986 (1986-12-05) abstract INTERNATIONALSEARCH REPORT Int lal Appilcatlon No 'formation on patent famlly members PCT/GB 99/01650 Patent document Publication Patent family Publication cited In search report date member (s) date WO 9742343 A 13-11-1997 AU 2746997 A 26-11-1997 EP 0901529 A 17-03-1999 WO 9742311 A 13-11-1997 JP 61275217 A 05-12-1986 NONE