WO2005041890A2 - Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same - Google Patents
Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same Download PDFInfo
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- WO2005041890A2 WO2005041890A2 PCT/US2004/036336 US2004036336W WO2005041890A2 WO 2005041890 A2 WO2005041890 A2 WO 2005041890A2 US 2004036336 W US2004036336 W US 2004036336W WO 2005041890 A2 WO2005041890 A2 WO 2005041890A2
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- Prior art keywords
- antigen
- haemophilus parasuis
- amount
- rhusiopathiae
- vaccine
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- 238000000034 method Methods 0.000 title claims description 37
- 241000186811 Erysipelothrix Species 0.000 title description 3
- 241000186810 Erysipelothrix rhusiopathiae Species 0.000 claims abstract description 91
- 241000606807 Glaesserella parasuis Species 0.000 claims abstract description 89
- 239000000427 antigen Substances 0.000 claims abstract description 41
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Classifications
-
- 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
- A61K39/085—Staphylococcus
-
- 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
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
-
- 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
- A61K39/0241—Mollicutes, e.g. Mycoplasma, Erysipelothrix
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- 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
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
Definitions
- the present invention is concerned with a vaccine for Erysipelothrix Rhusiopathiae (E. rhusiopathiae) and a vaccine for Haemophilus Parasuis (H. parasuis). More particularly, the present invention is concerned with a vaccine for conferring effective immunity against E. rhusiopathiae and H. parasuis and methods of making the same. Still more particularly, the present invention is concerned with a vaccine which can be administered in a single dose and provide a duration of immunity (DOI) of a desired length. Even more particularly, the present invention is concerned with a single dose vaccine which provides a DOI equivalent to the average life span of an animal receiving the vaccine.
- DOI duration of immunity
- E. rhusiopathiae is a gram-positive bacteria that is pathogenic to over 50 species of vertebrate and invertebrate animals including swine, sheep, lambs, cattle, ducks, turkeys, and humans.
- H parasuis is a gram-negative bacteria that is pathogenic to many animals, most notably swine.
- Vaccines against E. rhusiopathiae and H. parasuis are typically separate and consist of multiple doses given over the life span of an animal in order to confer effective immunity against E. rhusiopathiae and H. parasuis. There currently exists a vaccine against H. parasuis which can be administered in a single dose but a separate vaccination against E.
- problems with vaccines that require more than one dose include the time and expense needed to track which animals have received first and/or second or subsequent doses, to track when the first dose was given, to do the actual vaccination, the increased size of the animals between first and subsequent doses, the increased risk of injury to the animal and to the person giving the subsequent doses of vaccine, and the expense associated with providing multiple doses.
- a 1-dose regimen which confers effective immunity to an animal receiving the vaccination wherein the vaccine provides an extended DOI longer than is presently available through vaccines. What is further needed is a vaccine against E.
- rhusiopathiae that is administered in a single dose and provides a DOI of about six months. What is still further needed is a vaccine against E. rhusiopathiae and H. parasuis that provides a DOI of about six months after just a single dose of the vaccine.
- the present invention overcomes the deficiencies of the prior art and provides a distinct advance in the state of the art.
- the present invention provides a vaccine which can be administered in a single dose and which provides one or more of the following: 1) confers effective immunity against E. rhusiopathiae; 2) decreases the risk of developing clinical signs of E. rhusiopathiae infection; 3) induces an immune response against E. rhusiopathiae; and 4) has a DOI of at least four months, more preferably at least about five months, and most preferably at least about six months.
- the present invention also provides a combination vaccine that provides one or more of the following: 1) confers effective immunity against E.
- rhusiopathiae and/or H. parasuis decreases the risk of developing clinical signs of E. rhusiopathiae and/or H. parasuis through a single dose of vaccine; 3) induces an immune response against E. rhusiopathiae and/or H. parasuis; and 4) provides a DOI against E. rhusiopathiae and/or H. parasuis of at least about four months, more preferably at least about 132 days, more preferably at least about 5 months, and most preferably at least about six months or at least about 162 days.
- the combination vaccine can also be given as a single dose.
- rhusiopathiae vaccine includes a bacterial component of inactivated E. rhusiopathiae bacteria and a suitable adjuvant.
- the adjuvant can be selected based on the method of administration and may include mineral oil-based adjuvants such as Freund's complete and incomplete adjuvant, Montanide incomplete Seppic adjuvant such as ISA, oil in water emulsion adjuvants such as the Ribi adjuvant system, syntax adjuvant formulation containing muramyl dipeptide, or aluminum salt adjuvants.
- the adjuvant is a mineral oil-based adjuvant, most preferably ISA206 (S ⁇ PPIC, Paris, France).
- the composition may also include any one or combination of pharmaceutically acceptable carriers or excipients including, but not limited to, buffers, stabilizers, diluents, preservatives, and solubilizers.
- the vaccine is administered to animals susceptible to infection by E. Rhusiopathiae, preferably mammals, and still more preferably pigs, in any conventional manner, including oral, intranasal, intramuscular, intra-lymph node, intradermal, intraperitoneal, subcutaneous, and combinations thereof, but most preferably through intramuscular (IM) injection.
- the amount of the dose for intramuscular administration is preferably up to about 5 ml, still more preferably between 1 ml and 3 ml, and most preferably about 2 ml.
- rhusiopathiae-H. parasuis vaccine includes inactivated bacterial components of both E. rhusiopathiae and H. parasuis, together with a suitable adjuvant.
- the adjuvant is mineral-oil based, most preferably ISA206.
- the vaccine is administered to animals susceptible to infection by E. rhusiopathiae and/or H. parasuis, preferably mammals, and still more preferably pigs, in any conventional manner, including oral, intranasal, intramuscular, intra-lymph node, intradermal, intraperitoneal, subcutaneous, and combinations thereof, most preferably through intramuscular (IM) injection.
- IM intramuscular
- the amount of the dose when IM injection is the selected administration route is preferably up to about 5 ml, still more preferably between 1 ml and 3 ml, and most preferably about 2 ml.
- the amount of E. rhusiopathiae antigen in each dose should be enough to confer effective irnmunity against and decrease the risk of developing clinical signs resulting from E. rhusiopathiae infection to an animal receiving a vaccination therewith.
- rhusiopathiae antigen should be up to about 5 ml, more preferably between about 0.2 to 3 ml, still more preferably between about 0.3 to 1.5 ml, more preferably between about 0.4 to 0.8 ml, and still more preferably about 0.6 ml.
- the amount of H. parasuis antigen in each dose should be up to about 5 ml, more preferably between about 0.1 to 3 ml, still more preferably between about 0.15 to 1.5 ml, more preferably between about 0.2 to 0.6 ml, and still more preferably about 0.4 ml. In a different form of measurement, the amount of H.
- parasuis antigen in each dose should contain at least 1.5 x 10 7 cfu/dose, more preferably between about 1.5 x 10 8 to 1.5 x 10 10 cfu/dose and still more preferably about 1.5 x 10 9 cfu/dose.
- approximately 0.6 ml is E. rhusiopathiae antigen
- approximately 1.0 ml is the adjuvant
- approximately 0.4 ml is the H. parasuis antigen.
- the bacteria are inactivated by conventional inactivation techniques and especially conventional formalin inactivation techniques.
- Vaccines and compositions of the present invention are generally useful for inducing immune responses in animals as immune response-stimulating therapeutics or prophylactic vaccines.
- administration of the compositions or vaccines of the present invention results in an immune response that protects the vaccinated animal in various ways including a lessening in the severity or delay in the onset of clinical signs of E. rhusiopathiae and/or H. parasuis infection. Still more preferably, administration of the compositions or vaccines results in a reduced risk of developing clinical signs of E. rhusiopathiae and/or H. parasuis infection, even after exposure or challenge by virulent forms of E. rhusiopathiae and/or H. parasuis. In particularly preferred forms, administration of the composition or vaccine results in a complete prevention of these clinical signs.
- Various conventional methods can be used to determine if an immune response was induced in an animal.
- the animal receiving the composition or vaccine can be challenged with a virulent form of E. rhusiopathiae and/or H. parasuis and observed for the development of clinical signs of infection for a period of time after challenge.
- An alternative method of determining if an immune response was induced by administration of the composition or vaccine would be to assay a biological sample from the animal for antibodies to one or more antigens of E. rhusiopathiae and or H. parasuis. Such methods are common in the field and appropriate antibody assays could be determined by those of skill in the art.
- This example provides data as to the efficacy and duration of immunity against virulent E. rhusiopathiae following a preferred single dose H. parasuis-E. rhusiopathiae vaccine.
- Group 1 was composed of 23 pigs that received one 2mL intramuscular dose of H. parasuis-E. rhusiopathiae Bacterin with adjuvant ISA 206 (" ⁇ PE") (Boehringer Ingelheim Vetmedica, Inc., St. Joseph, MO) in the left neck on day 1.
- the E. rhusiopathiae antigen was included in each dose at the rate of 0.6mL volume of harvest antigen.
- Group 2 was composed of 14 pigs that received no treatment at all. On days 21, 54 and 161 of the study, all of the animals were bled to monitor seroconversion to vaccination.
- Vaccinates challenged with virulent E. rhusiopathiae 162 days after vaccination were well protected when compared to controls. 100% of the non-vaccinated controls developed the disease and 46% died following the challenge. By contrast, a single does of the HP ⁇ protected 95% of the challenged pigs and none of the pigs that received the vaccine died following challenge.
- the results of this study confirm the duration of immunity of at least 162 days for the HP ⁇ in a single dose regimen for prevention and control of erysipelas in nursery pigs aged 3 weeks of age or older.
- EXAMPLE 2 This example demonstrates the duration of immunity of a preferred single dose vaccine against virulent H. parasuis challenge after vaccination.
- the study for this example began with 36 pigs aged 3 to 4 weeks, none of which had been previously vaccinated using H. parasuis bacterin or vaccine. Throughout the example, the animals were provided food sufficient for their size, age and other physical characteristics. Water was supplied ad libitum. On day 1 of the example, the pigs were divided into two groups. Group 1 was composed of 23 pigs that received one 2mL intramuscular dose of H. parasuis Bacterin with adjuvant ISA 206 (" ⁇ PB") (Boehringer Ingelheim Netmidica, Inc., St. Joseph, MO) on day 1. The H parasuis antigen was included in each dose at the rate of 1.5 x 10 9 cfu/dose.
- ⁇ PB adjuvant ISA 206
- Group 2 the control group, was composed of 13 pigs who received no treatment at all.
- 11 pigs from Group 2 and 17 of the pigs from Group 1 were healthy and suitable for challenge with a virulent strain of H. parasuis.
- the 8 pigs (6 from Group 1 and 2 from Group 2) that did not receive challenge were unhealthy or had died for reasons unrelated to vaccination. All of the pigs were then observed for seven days for general health and the clinical signs of H. parasuis. A necropsy was performed on all of the animals that died during the trial and tissues were taken for bacterial confirmation of the cause of death when deemed necessary.
- Vaccinates challenged with virulent H. parasuis 132 days after vaccination were well protected when compared to controls. 73% of the non-vaccinated controls developed the disease and 55% died following the challenge. By comparison, a single dose of the HPB protected 94% of the challenged pigs. The vaccinates also experienced statistically significant lower mortality than controls due to H. parasuis.
- the results of this example confirm the duration of immunity of at least 132 days for the ⁇ PB in a single dose regimen in nursery pigs aged 3 weeks of age or older.
- EXAMPLE 3 This example describes a preferred method of preparing vaccine in accordance with the present invention.
- the composition of the E. rhusiopathiae-H. parasuis Bacterin includes strains SE-9 and Z- 1517 of E. rhusiopathiae and H. parasuis, respectively. These strains have been deposited with the ATCC and have been assigned deposit numbers PTA-6261 and PTS-6262, respectively.
- the seed materials of each are identified by characteristic growth patterns, Gram's stain reactions and biochemical tests. The virulence of the seed materials is determined by the ability to ldll mice and/or produce clinical signs in susceptible swine.
- the composition of the growth media for E. rhusiopathiae is found in Table 7.
- the composition of the growth media for H. parasuis is found in Table 8.
- Working Seeds of both strains should be stored frozen at ⁇ -60°C.
- the Master seed is returned to the liquid phase and 1 to 2 mL is inoculated into Worldng Seed Culture Media.
- the culture is then grown statically at 34 - 38°C for 6 to 24 hours.
- the cultures are then checked for purity by colony appearance on 5% sheep blood agar, cell morphology, and Gram's stain.
- An equal volume of stabilizer is added and dispensed into cryotubes for storage.
- the culture is then stirred at 34 - 38°C for 12 to 18 hours.
- the cultures are then checked for purity by colony appearance on 5% sheep blood agar, cell morphology, and Gram's stain.
- An equal volume of stabilizer is added and dispensed into cryotubes for storage.
- To inoculate E. rhusiopathiae 1-12 mL of Working Seed are inoculated into a glass vessel containing 500 to 18,000 mL media to prepare Production Seed. Up to 5% (v/v) Production Seed is inoculated into 15 to 750 L of media in 20 to 1000 L vessels to prepare Production Culture.
- Production Cultures are checked for purity by strealdng on 5% sheep blood agar, incubating at 34 - 38°C for 24 - 48 hours and observing colony morphology.
- 1-10 mL of Working Seed are inoculated into a glass vessel containing 500 to 18,000 mL media to prepare Production Seed.
- Up to 7% (v/v) Production Seed is inoculated into 14 to 750 L of media in 20 to 1000 L vessels to prepare Production Culture.
- Production Cultures are checked for purity by streaking on 5% sheep blood agar, supplemented with NAD streak, incubating at 34 - 38°C for 18 - 24 hours, and observing colony morphology. For the incubation of E.
- rhusiopathiae Seed Cultures are incubated at 34 - 38°C for 6 to 24 hours aerobically. Production Cultures are incubated at 34 - 38°C for 6 to 12 hours aerobically with optional agitation. For the incubation of H parasuis, Seek and Production Cultures are incubated at 34 - 38°C for 6 to 18 hours while stirring and with optional sparging with compressed air.
- p ⁇ is controlled by 2M Tris and the cultures are observed macroscopically during the incubation period for evidence of abnormal growth or signs of contamination. The media is turbid prior to inoculation. As growth increases, settling will be observed. Samples are taken to determine % transmittance.
- Purity is determined by colony mo ⁇ hology on 5% sheep blood agar and/or Gram's stain. A macroscopic observation of sufficient turbidity indicates that the culture is ready for harvest. This will occur between 6 - 12 hours following inoculation of Production Culture. For H. parasuis, cultures are observed macroscopically during the incubation period for evidence of abnormal growth or signs of contamination. Samples are taken to determine direct counts. Purity is determined by colony mo ⁇ hology on 5% sheep blood agar supplemented with an NAD streak and/or Gram's stain. A macroscopic observation of sufficient turbidity and a drop in p ⁇ ( ⁇ 7.0) indicates that a culture is ready for harvest.
- each Production Culture is sampled for purity testing and percent transmittance and each Production Culture vessel is prepared for inactivation.
- E. rhusiopathiae Production Cultures must exhibit typical growth as described, have a percent transmittance of ⁇ 40% at 620nm, and be free of any evidence of contamination.
- H. parasuis Production Cultures will have a microscopic count of ⁇ 5 x 10 7 organisms/mL and will be free of any evidence of contamination.
- Both strains are inactivated by the addition of formalin to the Production Cultures up to 0.5% (v/v). Inactivation is performed at 20 - 38° for 12 - 72 hours with optional agitation.
- the inactivated product is then stored at 2 to 7°C. Inactivation is confirmed by standard techniques.
- Adjuvant ISA 206 is added at 30-65% (w/v).
- the inactivated cultures are emulsified by homgenization with ISA 206.
- Sodium bisulfite solution 35% may be added to fractions or product to neutralize free formaldehyde.
- Formaldehyde solution may be added to fractions or at assembly of product not to exceed 0.2% concentration in completed product.
- the resulting products can then be concentrated in a sterile closed loop system utilizing a hollow fiber filtration with a 100,000 molecular weight cut off or by aseptically decanting settled culture to provide a concentration up to 2 x 10 10 organisms/mL.
- E. rhusiopathiae is standardized by percent transmittance and concentration.
- H. parasuis is standardized by direct count of organisms.
- EXAMPLE 4 This example demonstrates the assembly of the different vaccine components into a preferred vaccine in accordance with the present invention.
- Vaccine in accordance with the present invention can be made by combining 90,000 mL E. rhusiopathiae culture (which represents 90,000 mL of E. rhusiopathiae culture at 40% transmittance), 56,250 mL H. parasuis culture (which represents 56,250 mL of 4 x 10 9 organisms/mL ⁇ . parasuis culture), 2,250 mL sterile RO water, 150,000 mL ISA 206, and 1 ,500 L sterile 35% sodium bisulfate solution. Sterile 35% sodium bisulfate solution is also used as needed to neutralize formaldehyde levels to 0.2% formaldehyde solution.
- the pH of the resulting mixture is adjusted to 6.2 - 7.2 by the addition of ION sodium hydroxide or 5N hydrochloric acid as needed.
- ION sodium hydroxide or 5N hydrochloric acid as needed.
- Such a mixture should provide E. rhusiopathiae in a concentration equivalent to 0.3 - 0.9 mL of Harvest Culture at 40% transmittance and at least 1.5 x 10 9 H. parasuis organisms in each 2 mL dose.
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Abstract
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Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002544298A CA2544298A1 (en) | 2003-10-30 | 2004-10-29 | Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same |
EP04817502A EP1682174A4 (en) | 2003-10-30 | 2004-10-29 | Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same |
MXPA06004831A MXPA06004831A (en) | 2003-10-30 | 2004-10-29 | Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same. |
BRPI0415626-9A BRPI0415626A (en) | 2003-10-30 | 2004-10-29 | erysipelothrix rhusiopathiae - haemophilus parasuis vaccine and methods of employing it |
JP2006538414A JP2007509986A (en) | 2003-10-30 | 2004-10-29 | Ericeperross sulciopatia-Haeophilus paraswitzer vaccine and method of use |
AU2004285573A AU2004285573A1 (en) | 2003-10-30 | 2004-10-29 | Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US51586003P | 2003-10-30 | 2003-10-30 | |
US60/515,860 | 2003-10-30 | ||
US10/975,702 | 2004-10-28 | ||
US10/975,702 US8637047B2 (en) | 2003-10-30 | 2004-10-28 | Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2005041890A2 true WO2005041890A2 (en) | 2005-05-12 |
WO2005041890A3 WO2005041890A3 (en) | 2005-11-10 |
Family
ID=34556051
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2004/036336 WO2005041890A2 (en) | 2003-10-30 | 2004-10-29 | Erysipelothrix rhusiopathiae-haemophilus parasuis vaccine and methods of using the same |
Country Status (10)
Country | Link |
---|---|
US (1) | US8637047B2 (en) |
EP (1) | EP1682174A4 (en) |
JP (1) | JP2007509986A (en) |
KR (1) | KR20060105763A (en) |
AU (1) | AU2004285573A1 (en) |
BR (1) | BRPI0415626A (en) |
CA (1) | CA2544298A1 (en) |
MX (1) | MXPA06004831A (en) |
RU (1) | RU2006118694A (en) |
WO (1) | WO2005041890A2 (en) |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2980586A (en) * | 1958-06-09 | 1961-04-18 | Norden Lab Inc | Method of producing swine erysipelas vaccine |
CA2170839A1 (en) * | 1995-03-01 | 1996-09-02 | Janet Macinnes | Bacterial preparations, method for producing same, and their use as vaccines |
ZA982870B (en) * | 1997-04-10 | 1998-10-09 | Akzo Nobel Nv | Live attenuated bacteria of the species actinobacillus pleuropneumoniae |
US6025468A (en) * | 1998-06-20 | 2000-02-15 | United Biomedical, Inc. | Artificial T helper cell epitopes as immune stimulators for synthetic peptide immunogens including immunogenic LHRH peptides |
US6342231B1 (en) * | 1998-07-01 | 2002-01-29 | Akzo Nobel N.V. | Haemophilus parasuis vaccine and diagnostic |
US7172762B1 (en) * | 1999-01-29 | 2007-02-06 | Pfizer Inc. | Erysipelothrix rhusiopathiae antigens and vaccine compositions |
CA2290078C (en) * | 1999-01-29 | 2013-01-22 | Pfizer Products Inc. | Erysipelothrix rhusiopathiae antigens and vaccine compositions |
AU769539B2 (en) * | 1999-01-29 | 2004-01-29 | Zoetis Services Llc | Adjuvants for use in vaccines |
MY128159A (en) * | 2000-06-30 | 2007-01-31 | Wyeth Corp | Methods and composition for oral vaccination |
-
2004
- 2004-10-28 US US10/975,702 patent/US8637047B2/en active Active
- 2004-10-29 KR KR1020067010570A patent/KR20060105763A/en not_active Application Discontinuation
- 2004-10-29 MX MXPA06004831A patent/MXPA06004831A/en not_active Application Discontinuation
- 2004-10-29 EP EP04817502A patent/EP1682174A4/en not_active Withdrawn
- 2004-10-29 RU RU2006118694/13A patent/RU2006118694A/en not_active Application Discontinuation
- 2004-10-29 WO PCT/US2004/036336 patent/WO2005041890A2/en not_active Application Discontinuation
- 2004-10-29 CA CA002544298A patent/CA2544298A1/en not_active Abandoned
- 2004-10-29 AU AU2004285573A patent/AU2004285573A1/en not_active Abandoned
- 2004-10-29 JP JP2006538414A patent/JP2007509986A/en active Pending
- 2004-10-29 BR BRPI0415626-9A patent/BRPI0415626A/en not_active IP Right Cessation
Non-Patent Citations (1)
Title |
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See references of EP1682174A4 * |
Also Published As
Publication number | Publication date |
---|---|
EP1682174A2 (en) | 2006-07-26 |
JP2007509986A (en) | 2007-04-19 |
MXPA06004831A (en) | 2006-07-06 |
US20060093622A1 (en) | 2006-05-04 |
BRPI0415626A (en) | 2006-12-12 |
RU2006118694A (en) | 2007-12-10 |
WO2005041890A3 (en) | 2005-11-10 |
EP1682174A4 (en) | 2008-09-17 |
AU2004285573A1 (en) | 2005-05-12 |
CA2544298A1 (en) | 2005-05-12 |
US8637047B2 (en) | 2014-01-28 |
KR20060105763A (en) | 2006-10-11 |
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