Claims for Patent: 7,648,698

Summary for Patent: 7,648,698

Title:	Vaccine for veterinary and human medicine prophylaxis and therapy
Abstract:	The present invention relates to a novel vaccine, its use for immunoprophylaxis and/or the treatment of candidamycoses in human and veterinary medicine as well as methods for its preparation, wherein said vaccine consists of the combination of the Candida strains a1) Candida albicans CCM 8355 a2) Candida glabrata CCM 8356 a3) Candida krusei CCM 8357 and a4) an immunomudulating Propionibacterium acnes strain, and optionally pharmaceutically acceptable excipients, such as carriers, wherein the ratio of the components a1-a4 in the end product is a1:a2:a3:a4 is 10-20:10-20:10-20:40-70.
Inventor(s):	Braun; Dagmar (Greifswald-Insel Riems, DE), Vrzal; Vladimir (Ivanovice na Hane, CZ), Bittner; Libor (Vyskov, CZ), Koukalova; Dagmar (Olomouc, CZ)
Assignee:	Bioveta AG (CZ)
Application Number:	11/574,808
Patent Claims:	1. A vaccine comprising a combination of vaccine strains, wherein the combination consists of formaldehyde-inactivated Candida albicans strain CCM 8355, formaldehyde-inactivated Candida glabrata strain CCM 8356, and formaldehyde-inactivated Candida krusei strain CCM 8357 and heat-inactivated Propionibacterium acnes strain CCM 7083 in the ratio of 10-20:10-20:10-20:40-70. 2. The vaccine of claim 1, wherein the ratio is 15-20:15-20:15-20:40-55. 3. The vaccine of claim 1, wherein the ratio is 10-15:10-15:10-15:55-70. 4. The vaccine of claim l, wherein the total dry weight of all the vaccine strains is 2 to 10 mg per dose. 5. The vaccine of claim l, wherein the vaccine comprises less than 0.02% formaldehyde by weight. 6. The vaccine of claim l, wherein the vaccine is for oral, local, or parenteral administration. 7. The vaccine of claim 6, wherein the vaccine is for topical, vaginal, or rectal administration. 8. The vaccine of claim 6, wherein the vaccine is for oral administration and the ratio is 10:10:10:70. 9. The vaccine of claim 6, wherein the vaccine is for vaginal administration and the ratio is 15:15:15:55. 10. The vaccine of claim 6, wherein the vaccine is for rectal administration and the ratio is 20:20:20:40. 11. The vaccine of claim 1, wherein the vaccine is formulated in the form of a capsule, tablet, lozenge, pastille, syrup, oral suspension, oral emulsion, globulus, pill, suppository, vaginal ovule, ampoule, prefilled syringe, aerosol, insufflation, or mouthwash. 12. The vaccine of claim 1, wherein the vaccine is for use against local candidiasis, cutaneous candidiasis, or mucocutaneous candidiasis. 13. The vaccine of claim 1, wherein the local candidiasis affects the outer mucosa of the genital tract, the urogenital tract, the oral cavity, the gastrointestinal tract, or the skin. 14. The vaccine of claim 12, wherein the vaccine is for use against stomatitis (thrush) or vaginitis. 15. The vaccine of claim 1, wherein the vaccine further comprises one or more carriers or excipients suitable for veterinary administration. 16. The vaccine of claim 1, wherein the vaccine further comprises one or more carriers or excipients suitable for human administration. 17. The vaccine of claim 1, wherein the vaccine protects an animal against challenge with a Candida albicans strain, wherein the protection is measured by lack of isolation of the Candida albicans strain from kidneys of the animal. 18. A method of preparing the vaccine of claim 1 comprising the steps of: (a) separately cultivating the Candida albicans strain CCM 8355, the Candida glabrata strain CCM 8356, and the Candida krusei strain CCM 8357; (b) inactivating the Candida albicans strains with formaldehyde; (c) heat-inactivating the Propionibacterium acnes strain CCM 7083; (d) lyophilizing each of the inactivated strains; and (e) mixing the lyophilized inactivated strains of the Candida albicans strain CCM 8355, the Candida glabrata strain CCM 8356, the Candida krusei strain CCM 8357, and the Propionibacterium acnes strain CCM 7083 in the ratio 10-20:10-20:10-20:40-70 to obtain the vaccine. 19. The method of claim 18, wherein the total dry weight of all the vaccine strains is 2 to 10 mg per dose. 20. The method of claim 18, wherein the formaldehyde content of the vaccine is less than 0.02% by weight. 21. The method according to claim 18, wherein the vaccine strains are cultivated on a large scale in fermenters. 22. The method of claim 18, further comprising the step of mixing the lyophilized vaccine strains with one or more excipients. 23. The method according to claim 18, wherein the Candida albicans strains are cultivated on glucose peptone agar or Sabouraud's agar at 23.degree. to 27.degree. C. for 48 to 72 hours, or at 35.degree. C. to 39.degree. C. for 22 to 27 hours under aerobic conditions at a pressure of 0.1 to 0.2 bar and 90% to 98% atmospheric humidity and wherein the cells of the cultivated strains are subsequently washed with sterile water and disintegrated in three freeze and thaw cycles. 24. The method according to claim 18, wherein the Candida albicans strains are cultivated in Sabouraud's culture medium at 37.degree. C. for 24 to 48 hours under aerobic conditions and the cells of the cultivated strains are subsequently isolated using an ultrafiltration cartridge with a cut-off of 300 kDa followed by purification through repeated washing with sterile physiological saline, centrifugation at 4,500 g, washing with sterile water, and disintegration in three freeze and thaw cycles. 25. The method according to claim 18, wherein the Propionibacterium acnes strain is cultivated on a blood agar, reinforced clostridial agar, or Viande-Levure (VL) agar containing blood at 35.degree. C. to 39.degree. C. for 46 to 50 hours under strictly anaerobic conditions at 90% to 98% atmospheric humidity, followed by lysis of cells of the Propionibacterium acnes with sterile distilled water, extraction at 2.degree. C. to 8.degree. C. for 22 to 26 hours, and inactivation by heating up to three times to 56.degree. C. to 62.degree. C. for at least one hour at an interval of at least 24 hours. 26. The method of claim 18, wherein the Propionibacterium acnes strain is cultivated in a reinforced clostridial medium at 35.degree. C. to 39.degree. C. for 46 to 50 hours under strictly anaerobic and static conditions and the cells of the Propionibacterium acnes strain are isolated using an ultrafiltration cartridge with a cut-off of 300 kDa followed by purification through repeated washing with sterile physiological saline and centrifugation at 4,500 g, lysis of the cells with sterile distilled water, extraction at 2.degree. C. to 8.degree. C. for 22 to 26 hours, and inactivation by heating up to 56.degree. C. to 62.degree. C. for at least one hour at an interval of at least 24 hours. 27. The method according to claim 21, wherein the Candida albicans strains are cultivated in Sabouraud's culture medium having a pH of 5.6 to 7.2 at a temperature of 23.degree. C. to 27.degree. C. for 16 to 24 hours under aerobic conditions with 15% to 20% dissolved oxygen at a pressure of 0.1 to 0.2 bar against atmospheric pressure under addition of filtered atmospheric air at 40 to 50 rpm and the strains are isolated by means of industrial ultracentrifugation at 3,600 to 5,300 g, ultracentrifugation by means of an ultracentrifugation cartridge with a cut-off of 300 kDa, or a combination thereof. 28. The method according to claim 21 or 27, wherein the Propionibacterium acnes strain is cultivated in reinforced clostridial medium having a pH of 6.4 to 7.2 and a temperature of 35 to 39.degree. C. for 15 to 17 hours under strict anaerobic conditions with a maximum of 1% dissolved oxygen at a pressure of 0.1 to 0.2 bar against atmospheric pressure under addition of 10 L of a filtered mixture of N:CO.sub.2 (1:2) per minute at 40 to 50 rpm and the strain is isolated by means of industrial ultracentrifugation at 3,600 to 5,300 g, ultrafiltration by means of an ultrafiltration cartridge with a cut-off of 300 kDa, or a combination thereof.

Details for Patent 7,648,698

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2024-09-24