Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Patent
1993-04-19
1997-04-15
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
536 41, 536 5, 536 63, 424489, C07G 300, A61K 3900, C07H 1524, C07H 1700
Patent
active
056206909
DESCRIPTION:
BRIEF SUMMARY
The invention relates to immunogenic complexes such as two-dimensional lamellae having a honeycomb structure and in particular three-dimensional iscoms, which complexes are composed of at least one sterol, one saponin and, in the case of an iscom, also a phospholipid, as well as, optionally, at least one antigen generating an immune reaction.
EP-A-87,200,035.1 discloses a method for the preparation of immunogenic complexes, in which method an antigenic protein or peptide in dissolved or solubilised form is brought into contact with a solution which contains a detergent, a glycoside having a hydrophobic and a hydrophilic fragment, in at least the critical micelle-forming concentration (CMC), and also a sterol, the detergent is then removed and the immunogenic complex formed is purified. If the immunogenic complex formed is to have an "iscom" form, that is to say a cage-like structure which is built up from sub-units and has a diameter of about 35 nm or greater, a phospholipid must also be present in the abovementioned solution of the detergent, glycoside and sterol.
In the method according to this EP-A, saponins, such as saponins from Quillaja saponaria Molina, Aesculus hippocastanum or Gypsophilia struthium, are advantageously used as glycoside. Preferably, the product "Quil A" is used, this being a water-soluble extract from the bark of Quillaja saponaria Molina (K. Dalsgaard: Saponin Adjuvants III, Archiv fur die gesamte Virusforschung 44, 243-254 (1974)). More particularly, Quil A is a mixture of saponins of the triterpene class. Although Quil A lipid complexes and the like are regarded as effective antigen adjuvants essentially for amphipathic antigens, the mode of administration of complexes of this type is severely limited by the toxicity of Quil A. In this context, it is pointed out that, specifically, the toxicity of Quil A-containing immunogenic complexes is considered undesirably high for administration via, inter alia, the intraperitoneal (i.p.) route. This toxicity associated with Quil A is in all probability due to the haemolytic activity of this product.
WO 90/03184 discloses iscom matrices having an immunomodulatory activity. More particularly, this WO application relates to matrices which are composed of at least one lipid and at least one saponin. Advantageously, the lipid used is cholesterol. Examples of saponins are, in particular, triterpene saponins, preferably Quil A or one or more components of Quil A, which are indicated by the designations B4B, B2 and B3. With regard to the three abovementioned Quil A components, it is stated in WO 90/03184 that B4B, which has a molecular weight of 1862, is indeed able to form iscom structures with cholesterol but, however, has no adjuvant activity, whereas the B2 and B3 components (molecular weights of 1988 and 2150 respectively), which do have an adjuvant activity, form a bond with cholesterol but do not form an iscom-like structure therewith; adjuvant activity is understood to signify that the agent promotes the antibody response and/or cell-mediated immune response. Therefore, according to this WO 90/03184, either whole Quil A or both B4B and B2 or B3 must be used to prepare an iscom structure with cholesterol which has an adjuvant activity.
Since, as already stated above, Quil A has a certain toxic activity and the Quil A components disclosed in WO 90/03184 are not able both to form an iscom structure with cholesterol and have an adjuvant activity, the Applicant has sought other saponins which have a substantially reduced toxicity compared with Quil A and are also able to form an iscom structure having adjuvant activity.
Surprisingly, the Applicant has found that despite the discouraging data in WO 90/03184, there are some Quil A components which meet the requirements described above.
The invention therefore relates to immunogenic complexes, such as two-dimensional lamellae and in particular three-dimensional iscoms, which have an adjuvant activity and are composed of at least one sterol, at least one Quil A component as defined below and, in
REFERENCES:
patent: 4578269 (1986-03-01), Morein
patent: 4744983 (1988-05-01), Morein
patent: 4900549 (1990-02-01), DeVries et al.
patent: 4981684 (1991-01-01), MacKenzie et al.
patent: 5057540 (1991-10-01), Kensil et al.
patent: 5254339 (1993-10-01), Morein
patent: 5273965 (1993-12-01), Kensil et al.
Buroru, Morein, "Adjuvant-Lipid Complexes for Use as Modified Adjuvants in Preparing Vaccines", Chemical Abstracts, vol. 113, No. 21, Abstract No. 189646f, Nov. 1990, p. 573.
Kersten et al. (1988) Infection and Immunity 56(2) 432-438.
Morein et al. (1987) Immunolog Today 8(11):333-338.
Beuvery Eduard C.
Kersten Gideon F. A.
Spiekstra Arjan
Van Der Werken Gerrit
De Stat Der Nederlanden Vertegenwoordigd Door De Minister Van We
Housel James C.
Minnifield N. M.
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