EP1158991A1 - Treatment of asthma - Google Patents
Treatment of asthmaInfo
- Publication number
- EP1158991A1 EP1158991A1 EP00911507A EP00911507A EP1158991A1 EP 1158991 A1 EP1158991 A1 EP 1158991A1 EP 00911507 A EP00911507 A EP 00911507A EP 00911507 A EP00911507 A EP 00911507A EP 1158991 A1 EP1158991 A1 EP 1158991A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- lam
- immunogenic
- vaccine
- asthma
- patient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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
- A61K39/35—Allergens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/739—Lipopolysaccharides
-
- 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
- A61K39/04—Mycobacterium, e.g. Mycobacterium tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- 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
- A61K2039/541—Mucosal route
- A61K2039/544—Mucosal route to the airways
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- This invention relates to the treatment of asthma. More particularly, it relates to both therapeutic treatment of asthma sufferers and to preventative (prophylactic) treatment of non-asthmatics against asthma.
- Asthma is a chronic inflammatory disorder of the airways in which many cells play a role, including mast cells and eosinophils. In susceptible individuals this inflammation causes symptoms which are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment, and causes an associated increase in airway responsiveness to a variety of stimuli.
- Asthma can be inherited, is not contagious and may be chronic and persistent or occurring in the form of attacks which are periodic and usually at least partly reversible. Attacks vary in severity and frequency from person to person. Many factors may contribute to the development of asthma including exposure to inhaled allergens such as pollens, mold spores, house dust mites and animal dander. In an individual who has developed asthma, many stimuli can trigger asthma attacks including allergens, viral respiratory infections (colds or the flu), irritants in the air (smoke, air pollution, perfume), damp, cold weather, and exercise.
- the muscles around the bronchial tubes tighten and the linings of the bronchial tubes swell (become inflamed) and produce thick mucus, thereby decreasing the internal diameter of the tubes. These changes increase resistance to the flow of air making it hard to breathe.
- the bronchial tubes are of normal size.
- Asthma is a common disease among both children and adults. An estimated 7% of people in the United States have been diagnosed as asthmatic. The corresponding figure for New Zealand is about 10% (Burney, P. et al. (1996) Variations in the Prevalence of Respiratory Symptoms, Self-Reported Asthma Attacks, and Use of Asthma Medication in the European Community Respiratory Health Survey. Eur. Respir. J. 9:687-695). The occurrence of asthma in both Western and developing countries has increased markedly over the last 30 years. This relatively short time frame suggests that environmental rather than genetic factors are at work.
- asthma is an atopic disorder in which the underlying process is due to an allergic response to common environmental allergens.
- This allergic response is a function of the immune system characterised by activation and recruitment of eosinophils to the lung causing the characteristic chronic swelling and inflammation of the airways that affects the breathing of sufferers.
- the pharmaceutical treatment of asthma includes several different classes of drugs, including beta agonists, topical or oral steroids and theophyllines. If used appropriately, such treatments may keep asthma systems from developing or relieve them when they are present. Beta agonists and theophyllines primarily act by relaxing the muscles surrounding the airways while steroids act to reduce (and even prevent) inflammation and mucus production. Other medications exist and more are being developed due to the growing interest in and concern over the prevalence, morbidity and mortality of asthma world-wide.
- Th2 lymphocytes Th2 lymphocytes
- IL-4 interleukin-4
- IgE immunoglobulin E
- B cells B cells
- IgE immunoglobulin E
- Activation of mast cells by allergens releases histamine and other mediating chemicals that trigger an acute inflammatory response, including mucus production.
- Eosinophils release mediators including cytotoxins which lead to inflammation and necrosis of the bronchial epithelium.
- the localised recruitment and activation of eosinophils together with the resultant tissue damage is termed "eosinophiiia".
- One immunological approach to meet this need involves Mycobacte ⁇ um bovis - Bacillus Calmette-Guerin (BCG).
- BCG Mycobacte ⁇ um bovis - Bacillus Calmette-Guerin
- BCG as an organism and as BCG-Polysaccharide Nucleic Acid has also been reported as being used in the treatment of asthma in China (see, for example, China J. Paedia (1991); 39(3): 165- 167, Guangzhou Medical Journal 1984; 15(2): 16- 18) and Ada of Hu-Nan Medical University 1992; 17:365-367. Intact BCG is reported as being administered both alive and dead. The reported routes of administration vary between intramuscular injection and scratch vaccination.
- the present invention is directed to an alternative immunological approach involving, as active agent, a type of Upopolysaccharide in immunogenic form.
- the lipopolysaccharide is lipoaribinomannan (LAM).
- Lipopolysaccharides have been included in immunological compositions previously.
- US Patent specification 5,853,737 discusses various methods of inducing a CDl restricted immune response and teaches of a vaccine containing CD l -presented non-polypeptide hydrophobic antigens and in particular a lipoarabinomannan (LAM) antigen.
- LAM lipoarabinomannan
- LAM has not been employed as an immunoactive agent in a vaccine for treating asthma, either prophylactically or therapeutically, where the vaccine is administered to the airways of a patient.
- the invention provides a vaccine for inducing an immune response in a patient effective in the prophylactic treatment against, or therapeutic treatment of, asthma which comprises, as active agent, immunogenic lipoarabinomannan (LAM) formulated for respiratory administration to said patient.
- LAM immunogenic lipoarabinomannan
- immunological LAM means LAM other than as part of an intact mycobacterial organism, which LAM is capable of inducing an immune response in a patient.
- said immunogenic LAM is substantially free of bacterial nucleic acid.
- prophylactic treatment against asthma means treatment of a non- asthmatic patient to prevent or at least reduce the likelihood of the patient becoming asthmatic.
- terapéutica treatment of asthma encompasses preventing, or reducing the severity of the symptoms of an asthmatic episode in an asthmatic patient, inclusive of bronchial inflammation and eosinophiiia.
- respiratory administration means administration to the airways of a patient, including administration intranasally and by inhalation through the mouth to reach the respiratory tract.
- the immune response induced is a non-CD 1 restricted immune response.
- the invention further provides a vaccine for reducing the severity of asthma comprising an immunologically effective amount of immunogenic LAM formulated for respiratory administration.
- the invention provides a vaccine for reducing the risk of developing asthma comprising an immunologically effective amount of immunogenic LAM formulated for respiratory administration.
- said immunogenic LAM is isolated from a mycobacterium, more conveniently isolated from an M. bovis organism and most conveniently is isolated from M. bovis strain AN5.
- said LAM contains, as its saccharide component, from 27% to 52% mannose and from 73% to 48% arabinose, more preferably, from 40% to 50% mannose and from 60% to 50% arabinose, and most preferably approximately 45% mannose and approximately 55% arabinose.
- said immunogenic LAM prefferably be a fluid, and preferably in the form of a solution or suspension.
- the vaccine will further comprise a respiratorially acceptable adjuvant, which may include a detergent or surfactant component.
- a secondary immunogen selected from one or more Thl type immune response inducing substances may also be present.
- Mycobacterium bovis (Bacillus Calmette-Guerin) is included as said Thl type immune response inducing substance.
- the invention provides a method of prophylactically treating a non-asthmatic patient against asthma which comprises the step of inducing an immune response in said patient by respiratorially administering an effective amount of immunogenic LAM.
- the invention provides a method of therapeutically treating asthma in a patient which comprises the step of inducing an immune response in said patient by respiratorially administering an effective amount of immunogenic LAM.
- the immune response induced is not a CD l restricted immune response.
- said immunogenic LAM is administered in the form of a vaccine as described above.
- the immunogenic LAM will be administered by inhalation through the mouth or intranasally to said patient.
- the invention provides the use of immunogenic LAM in the preparation of a medicament for the therapeutic treatment of asthma.
- the invention provides the use of immunogenic LAM in the preparation of a medicament for prophylactic treatment of a non-asthmatic against developing asthma.
- the immunogenic LAM is isolated from a mycobacterium, more preferably an M. bovis organism, and most preferably M. bovis strain AN5.
- the immunogenic LAM contains, as its saccharide component, from 27% to 52% mannose and from 73% to 48% arabinose, more preferably from 40% to 50% mannose and from 60% to 50% arabinose and most preferably approximately 45% mannose and approximately 55% arabinose.
- said immunogenic LAM be combined with a respiratorially acceptable adjuvant such that the medicament is formulated for respiratory administration.
- the invention provides a device for prophylactically or therapeutically treating asthma which includes a container from which a vaccine as described above can be dispensed to the airways of a patient in need of such treatment.
- the device will conveniently be one from which said vaccine is dispensable for inhalation through the mouth of a patient, or intranasally dispensable.
- Figure 1 is a graph showing number of cells recovered per ml of bronchoalveolar lavage (BAL) exudate.
- Figure 2 is a graph showing total number of cells recovered by BAL.
- Figure 3 is a graph showing the percentage of eosinophils recovered by BAL.
- Figure 4 is a graph showing the percentage of macrophages recovered by BAL.
- Figure 5 is a graph showing number of eosinophils recovered per ml of BAL exudate.
- Figure 6 is a graph showing total number of eosinophils recovered by BAL.
- Figure 7 is a graph showing the dose response curve for LAM as determined by numbers of eosinophils recovered per ml of BAL exudate.
- Figure 8 is a graph showing the effect of LAM in CD 1 Knock Out mice as determined by the number of eosinophils recovered per ml of BAL exudate.
- the present invention offers an approach to reducing the severity of airway eosinophiiia and thus asthma in an asthmatic and/ or for reducing the risk of developing airway eosinophiiia and thus asthma in a non-asthmatic by introducing to the airways biologically active amounts of lipoarabinomannan (LAM) in an immunogenic form.
- LAM lipoarabinomannan
- LAM is present in actinomycetes, which are a distinctive lineage of Gram-positive bacteria.
- Members of this lineage include Rhodococcus equi, Corynebacterium diphtheriae, Corynebacterium matruchotii, Gordona rubropertincta, Gordona terrae, Rhodococcus rhodnii and Tsukamurella paurometabolum.
- LAM mycobacteria
- LAM lipoglycan of the mycobacterial cell wall
- LAM can therefore be obtained by isolation from any suitable actinomycetes organism. It is however preferred that the immunogenic LAM for use in the invention be obtained from mycobacteria, particularly pathogenic mycobacteria, or from attenuated strains of pathogenic mycobacteria. However, LAM from non-pathogenic avirulent mycobacteria is by no means excluded.
- TNF- ⁇ Tumour Necrosis Factor-alpha
- mycobacteria from which LAM can be obtained are therefore M. bovis, M. tuberculosis, M. vaccae and M. paratuberculosis, with M. bovis organisms such as M. bovis strain AN5 being presently preferred.
- the LAM can be isolated from such bacteria, and in particular from mycobacteria, using techniques which are standard in the art. By way of example, the procedure of Severn et al, J. Microb. Methods, 28, 123-30 (1997) can be employed.
- Isolated LAM will conveniently be purified for use in the present invention.
- the effect of this will be to exclude other bacterial components (including bacterial nucleic acid) from the LAM.
- art standard techniques can be employed such as those described by Severn et al.
- the saccharide composition of the immunogenic LAM can vary. Generally, any lipoglycan with a saccharide component containing both arabinose and mannose (and therefore qualifying as a LAM) can be used. However, it is preferred for there to be at least 27% of mannose present, with a preferred saccharide composition varying from 27% to 52% mannose and 73% to 48% arabinose.
- the saccharide component will include 40% to 50% mannose and 60% to 50% arabinose, with one particularly preferred LAM having a saccharide component which is approximately 45% mannose and 55% arabinose.
- the LAM is obtained and preferably purified, it is formulated for respiratory administration.
- Respiratory administration requires delivery of the LAM to the airways of the patient to be treated. Generally, this will involve delivery through the mouth or intranasally. Often, inhalation by the patient will provide the motive force to the LAM.
- respiratory administration can also involve delivery by propellant, including in the form of an aerosol generated using a jet or ultrasonic nebuliser. This is presently preferred.
- the LAM will conventionally be in a fluid form. This can be as a powder or as a solution or suspension (particularly for aerosol application) .
- the LAM will generally also be formulated for respiratory administration together with a respiratorially acceptable adjuvant.
- the selection of the adjuvant will be dependent upon the formulation and mode of dispensing involved, but will in any case be a matter of routine choice for the skilled worker in this field.
- the LAM is to be administered via a nebuliser-generated aerosol
- the LAM will be in the form of a solution or suspension which will contain such adjuvant components.
- One such optional but preferred component is a non- toxic detergent or surfactant. Examples include a Polysorbate 80, beractant (Survanta Susp (Abbott)) and colfosceril palmitate (Exosurf Neonatal (Glaxo Wellcome)).
- an additional immunogen in the solution or suspension for administration as an aerosol.
- an immunogen will generally be a Thl type immune response inducing substance.
- One such substance which can be included is BCG, alive or dead, but with dead being preferred.
- BCG is included as a secondary immunogen
- a non-clumping agent such as Bovine Serum Albumin
- the LAM vaccine can be formulated for administration as a powder, for example using lactose capsules as a delivery vehicle in a dry powder inhaler.
- M. bovis strain AN5 obtained from Central Veterinary Laboratories, Weybridge, UK was grown as pellicles on modified Reid's synthetic medium. The cells were killed by heating at 100°C for 3 hours, washed with buffered saline and recovered by centrifugation. The cells were slurried in TBS, cooled and extruded by passing though a French pass. The disrupted cells were digested with RNAse (Boehringer Mannheim) and DNAse (Boehringer Mannheim) at 37°C and then 60°C.
- RNAse Boehringer Mannheim
- DNAse Boehringer Mannheim
- Triton X-114 solution was added to the lysed cells, cooled on ice and stirred for 16 hours at 4°C. The cellular debris was removed by centrifugation and the supernatant was incubated at 37°C to induce phase separation.
- the lipoglycans were recovered from the lower Triton X- 114 phase following precipitation by the addition of ethanol and centrifugation. The extract was further purified by treatment with Proteinase K and isolated by ultra- centrifugation. The lipoglycans were resolved into their separate species by size exclusion chromatography on Sephacryl s-200. Fractions containing LAM were identified using SDS-PAGE analysis.
- LAM The purity of the combined LAM fractions was investigated. LAM was deemed pure based on the following criteria: 0% protein as indicated by the BCA protein assay performed as described by Severn et al (1997), absence of nitrogen as indicated by elemental analysis of the purified extracts, and the absence of ribose or deoxyribose in the glycose analysis (Severn et al (1997)).
- the purified LAM was hydrolysed and acetylated (as described by Severn et al (1997)) and the resulting mixture of saccharides analysed by GLC as described by Severn et al (1997)).
- the mixture was comprised of 45% mannose and 55% arabinose confirming that the saccharide component of the lipoglycan is arabomannin.
- OVA ovalbumin
- antigen specific Th2 cells were primed to OVA in test mice by two successive intraperitoneal immunisations 14 days apart with OVA and by administration of an intranasal challenge of OVA 14 days after the second intraperitoneal immunisation.
- PBS was administered intranasally to 5 primed mice as a control.
- Figures 1 to 6 show the results of these experiments.
- Figures 1 and 2 show the number of cells recovered per ml and in total.
- Figures 3, 5 and 6 show that immunisation with high dose LAM gives rise to a reduction in eosinophil numbers equal to or greater than the reduction seen with whole live or dead BCG. This implies that LAM may be the active component in BCG that suppresses airway eosinophiiia.
- Figure 4 shows that the number of macrophages in mice immunised with whole BCG (live or dead) is equivalent to the number found in mice immunised with high doses of LAM. This is supportive of a finding that T ⁇ F- ⁇ (which activates macrophages) is stimulated by LAM.
- the OVA induced airway eosinophiiia mouse model of atopic airway inflammation described in section C l was used, together with a CD l Knock-Out (KO) mouse model.
- the CD l KO mice used were bred in turn from CD l KO mice, prepared as described by Chen et al, Immunity, 6:459-467 (1997), and confirmed as having CDl KO status by standard techniques. Briefly, these involved FACS staining of the mice as follows: Mice were tail bled and the cells spun down into a pellet. The cells were treated with ACK lysis buffer and then spun down into a pellet. The pellet was resuspended in FACS buffer (PBS + 2% foetal calf serum + 0.1% sodium azide). The cells were then stained with PE-anti-CDld and analysed by flow cytometry to identify CD l KO mice.
- FACS buffer PBS + 2% foetal calf serum + 0.1% sodium azide
- Figure 7 shows the effective dose of LAM with respect to a reduction in eosinophil numbers compared to a PBS control.
- Figure 8 shows that immunisation with LAM gives rise to a reduction in eosinophil numbers in CDl knockout mice. This shows that the LAM-induced reduction in eosinophil numbers is not dependent on the CD l pathway, and the immune response is not CD 1 restricted.
- the primary application of the invention is in anti-asthma treatment. That treatment may be prophylactic, to prevent or reduce the risk of non-asthmatics developing asthma, or therapeutic, to suppress established disease in an asthmatic.
- the LAM-containing vaccines of the invention are formulated for respiratory administration, which will preferably involve the inhaled route for convenience.
- the presently preferred mode of administration will involve the use of a dispensing device, of which a container of LAM vaccine forms a part.
- That device can be a nebuliser, particularly a jet nebuliser such as that known as the Omron CX (Omron Healthcare, Singapore), the Medic Aid Ventstream or the Wright nebuliser (Aerosol Medicals, Colchester, UK) (where the vaccine is to be administered as an aerosol) or a dry powder inhalation device (such as the devices known as the Accuhaler and Diskhaler (Glaxo Wellcome)).
- a jet nebuliser such as that known as the Omron CX (Omron Healthcare, Singapore), the Medic Aid Ventstream or the Wright nebuliser (Aerosol Medicals, Colchester, UK) (where the vaccine is to be administered as an aerosol) or a dry powder inhalation device (such as the devices known as the Accuhaler and Diskhaler (Glaxo Wellcome)).
- Respiratorially administered LAM has shown significant efficacy in reducing eosinophil numbers and in turn in reducing bronchial inflammation. The implications of this in both resisting the onset, and reducing the severity, of an asthma episode, and in treating non-asthmatics against developing asthma will be apparent to those skilled in this art.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ33466499 | 1999-03-15 | ||
NZ33466499 | 1999-03-15 | ||
PCT/NZ2000/000027 WO2000054783A1 (en) | 1999-03-15 | 2000-03-15 | Treatment of asthma |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1158991A1 true EP1158991A1 (en) | 2001-12-05 |
EP1158991A4 EP1158991A4 (en) | 2003-05-14 |
Family
ID=19927171
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00911507A Withdrawn EP1158991A4 (en) | 1999-03-15 | 2000-03-15 | Treatment of asthma |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1158991A4 (en) |
AU (1) | AU3337300A (en) |
CA (1) | CA2367447A1 (en) |
WO (1) | WO2000054783A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1649869A1 (en) * | 2004-10-21 | 2006-04-26 | Vakzine Projekt Management GmbH | Combination of a recombinant mycobacterium and a biologically active agent as a vaccine |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997034149A1 (en) * | 1996-03-12 | 1997-09-18 | Stefan Svenson | Method of diagnosing a mycobacterial disease and immunoassay kit |
US5853737A (en) * | 1992-12-10 | 1998-12-29 | Brigham And Women's Hospital | Method for inducing a CD1-restricted immune response |
-
2000
- 2000-03-15 AU AU33373/00A patent/AU3337300A/en not_active Abandoned
- 2000-03-15 WO PCT/NZ2000/000027 patent/WO2000054783A1/en not_active Application Discontinuation
- 2000-03-15 EP EP00911507A patent/EP1158991A4/en not_active Withdrawn
- 2000-03-15 CA CA002367447A patent/CA2367447A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5853737A (en) * | 1992-12-10 | 1998-12-29 | Brigham And Women's Hospital | Method for inducing a CD1-restricted immune response |
WO1997034149A1 (en) * | 1996-03-12 | 1997-09-18 | Stefan Svenson | Method of diagnosing a mycobacterial disease and immunoassay kit |
Non-Patent Citations (1)
Title |
---|
See also references of WO0054783A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO2000054783A1 (en) | 2000-09-21 |
CA2367447A1 (en) | 2000-09-21 |
AU3337300A (en) | 2000-10-04 |
EP1158991A4 (en) | 2003-05-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8404250B2 (en) | Gram positive bacteria preparations for the treatment of diseases comprising an immune dysregulation | |
Horvat et al. | Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease | |
US20040022793A1 (en) | Vaccine comprising active agent immunogenic acyl glyceryl phosphatidylinositol manno-oligosaccharide | |
Christ et al. | Enhancement of Th1 lung immunity induced by recombinant Mycobacterium bovis Bacillus Calmette-Guerin attenuates airway allergic disease | |
KR101854904B1 (en) | Non-typeable haemophilus influenzae vaccines and their uses | |
Nelson | The return of the mixed respiratory bacterial vaccine. | |
WO2000054783A1 (en) | Treatment of asthma | |
US20080044440A1 (en) | Vaccine Formulated For Administration To Mucosa Of The Lungs | |
CA2861074C (en) | Mtb-c vaccine against asthma | |
AU779163B2 (en) | Methods and compounds for the treatment of immunologically-mediated diseases using mycobacterium vaccae | |
US6569436B1 (en) | Method of using a vaccine | |
US20040247622A1 (en) | Methods and compounds for the treatment of immunologically-mediated diseases using Mycobacterium vaccae | |
EP2139501B1 (en) | Use of francisella tularensis for prevention and treatment of allergic airway disorders |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20011003 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
AX | Request for extension of the european patent |
Free format text: AL;LT;LV;MK;RO;SI |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: THE UNIVERSITY OF OTAGO Owner name: AGRESEARCH LIMITED Owner name: THE MALAGHAN INSTITUTE OF MEDICAL RESEARCH |
|
A4 | Supplementary search report drawn up and despatched |
Effective date: 20030328 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: 7A 61K 31/739 A Ipc: 7A 61P 11/06 B Ipc: 7A 61K 35/74 B Ipc: 7A 61P 37/08 B |
|
17Q | First examination report despatched |
Effective date: 20040204 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20040615 |