Drug – bio-affecting and body treating compositions – Nonspecific immunoeffector – per se ; or nonspecific...
Reexamination Certificate
2001-07-31
2003-04-22
Lambkin, Deborah C. (Department: 1626)
Drug, bio-affecting and body treating compositions
Nonspecific immunoeffector, per se ; or nonspecific...
C558S166000, C558S172000
Reexamination Certificate
active
06551600
ABSTRACT:
BACKGROUND OF THE INVENTION
Vaccines have proven to be successful, highly acceptable methods for the prevention of infectious disease. They are cost effective, and do not induce antibiotic resistance to the target pathogen or affect normal flora present in the host. In many cases, such as when inducing anti-viral immunity, vaccines can prevent a disease for which there are no viable curative or ameliorative treatments available.
Vaccines function by triggering the immune system to mount a response to an agent, or antigen, typically an infectious organism or a portion thereof that is introduced into the body in a non-infectious or non-pathogenic form. Once the immune system has been “primed” or sensitized to the organism, later exposure of the immune system to this organism as an infectious pathogen results in a rapid and robust immune response that destroys the pathogen before it can multiply and infect enough cells in the host organism to cause disease symptoms.
The agent, or antigen, used to prime the immune system can be the entire organism in a less infectious state, known as an attenuated organism, or in some cases, components of the organism such as carbohydrates, proteins or peptides representing various structural components of the organism.
In many cases, it is necessary to enhance the immune response to the antigens present in a vaccine in order to stimulate the immune system to a sufficient extent to make a vaccine effective, i.e., to confer immunity. Many protein and most peptide and carbohydrate antigens, administered alone, do not elicit a sufficient antibody response to confer immunity. Such antigens need to be presented to the immune system in such a way that they will be recognized as foreign and will elicit an immune response. To this end, additives (adjuvants) have been devised which immobilize antigens and stimulate the immune response.
The best known adjuvant, Freund's complete adjuvant, consists of a mixture of mycobacteria in an oil/water emulsion. Freund's adjuvant works in two ways: first, by enhancing cell and humoral-mediated immunity, and second, by blocking rapid dispersal of the antigen challenge (the “depot effect”). However, due to frequent toxic physiological and immunological reactions to this material, Freund's adjuvant cannot be used in humans.
Another molecule that has been shown to have immunostimulatory or adjuvant activity is endotoxin, also known as lipopolysaccharide (LPS). LPS stimulates the immune system by triggering an “innate” immune response—a response that has evolved to enable an organism to recognize endotoxin (and the invading bacteria of which it is a component) without the need for the organism to have been previously exposed. While LPS is too toxic to be a viable adjuvant, molecules that are structurally related to endotoxin, such as monophosphoryl lipid A (“MPL”) are being tested as adjuvants in clinical trials. Currently, however, the only FDA-approved adjuvant for use in humans is aluminum salts (Alum) which are used to “depot” antigens by precipitation of the antigens. Alum also stimulates the immune response to antigens.
Thus, there is a recognized need in the art for compounds which can be co-administered with antigens in order to stimulate the immune system to generate a more robust antibody response to the antigen than would be seen if the antigen were injected alone or with Alum.
SUMMARY OF THE INVENTION
In one aspect, the present invention is directed to novel compounds that function as immunological adjuvants when co-administered with antigens such as vaccines for bacterial and viral diseases.
In a second aspect, the present invention is directed to novel adjuvant formulations which comprise at least one of the adjuvant compounds of the invention.
In a third aspect, the invention is directed to novel immunostimulatory compositions which comprise an antigen and at least one of the adjuvant compounds of the invention.
In another aspect, the present invention is directed to methods for the immunization of an animal by co-administration of a compound of the invention with an antigen against which the animal is to be immunized.
REFERENCES:
patent: 5904925 (1999-05-01), Exner
patent: 5961970 (1999-10-01), Lowell
patent: 5985284 (1999-11-01), Exner
patent: 6136797 (2000-10-01), Zilch et al.
patent: 6146632 (2000-11-01), Momin et al.
patent: 6165502 (2000-12-01), Oleske et al.
patent: 6172049 (2001-01-01), Dwyer et al.
patent: 6180111 (2001-01-01), Stein et al.
patent: 6355257 (2002-03-01), Johnson et al.
patent: 6437165 (2002-08-01), Mandala et al.
Inoue K., 1968, Chemical and Pharmceutical Bulletin, vol. 16, No. 1, “Immunological Studies of Phospholipids. II. Syntheses of Cardiolipin and its Analogues”, pp. 76-81.
Duralsky A.A. et al, Mar. 19, 1998, Tetrahedron Letters, NL, Elsevier Science Publishers, Amsterdam, vol. 39, No. 12, “Synthesis of Isotopically Labelled Cardiolipins”, pp. 1607-1610.
Jain M.K. et al, 1986, Biochim. Biophys. Acta (BBACAQ, 00063002); vol. 860 (3); “Effect of the Structure of Phospholipid on the Kinetics of Intravesicle Scooting of Phospholipase A2”, pp. 462-474.
Inoue K et al, 1969, Chem. Phys. Lipids (CPL1A4); vol. 3, “Immunochemical Studies Phospholipids, IV. Reactivities of Antiserum Against Natrual Cadiolipin and Synthetic Cardiolipin Analogs-Containing Antigens”. pp. 70-7.
Inoue K. et al. 1967, Chem. Phys. Lipids (CPLIA4), vol. 1 (4); “Immunochemical Studies of Phopholipids. I. Reactivity of Various Synthetic Cardiolipin Derivatives with Wassermann Antibody”, the whole document.
Gregoriadies G et al, Aug. 1, 1996, Journal of Controlled Release, NL, Elsevier Science Publishers B.V. Amsterdam, vol. 41, No. 1/02, “Liposomes As Immunological Adjuvants and Vaccine Carriers”, pp. 49-56.
Vogel F.R., Jan. 1, 1995, Annals of the New York Academy of Sciences, “Immunologic Adjuvants for Modern Vaccine Formulations”, pp. 153-160.
Weissig V. et al, 1990, Wiss. Z. Martin Luther Univ. Halle-Wittenberg, Math. Naturwiss. Reihe (WMHMAP), 01381504), vol. 39(6), “Funtionlized Liposomes with Immunological Adjuvant Effects” pp. 101-9.
P. Hoffmann, K.-H. Wiesmuller, J. Metzger, G. Jung, and W.G. Bessler. “Induction of Tumor Cytoxcity in Murine Bone Morrow-Derived Macrophages by Two Synthetic Lipopeptide Analogues.” Biol. Chem. Hoppe-Seyler, 1989, 370, 575-582.
K.-H. Wiesmuller, G. Jung and G. Hess. “Novel low-molecular-weight synthetic vaccine against foot-and-mouth disease containing a potent B-cell and macrophage activator.” Vaccine, 1989, 7, 29-33.
K.-H. Wiesmuller, W.G. Bessler, and G. Jung. “Solid phase peptide synthesis of lipopeptide vaccines eliciting epitope-specific B-, T-helper and T-killer cell response.” Int. J. Peptide Protein Res. 1992, 40, 255-60.
J.-P. Defoort, B. Nardelli, W. Huang, D.D. Ho, and J.P. Tam. “Macromolecular assemblage in the design of a synthetic AIDS vaccine.” Proc. Natl. Acad. Sci. USA, 1992, 89, 3879-3883.
T. Toyokumi, B. Dean, S. Cai, D. Biovin S. Hakomori, and A.K. Singhal. “Synthetic Vaccines: Synthesis of a Dimeric Tn Antigen-Lipopeptide Conjugate That Elicits Immune Rsponses Against tn-Expressing Glycoproteins,” J.Am. Chem. Soc. 1994, 116, 395-396.
F. Reichel, P.R. Ashton, and G.-J. Boons. “Synthetic carbohydrate-based vaccines: synthesis of an L-glycero-D-manno-heptose antigen-T-epitope-lipopeptide conjugate,” Chem. Commun. 1997, 2087-2088.
H. Kamitakahara, T. Suzuki, N. Nishigori, Y. Suzuki, O. Kanie, and C.-H. Wong. “A Lysogangliside/poly-L-glutamic Acid Conjugate as a Picomolar Inhibitor of Influenza Hemagglutinin.” Angew. Chem. Int. Ed. 1998, 37, 1524-1528.
W. Dullenkopf, G. Ritter, S.R. Fortunato, L.J. Old, and R.R. Schmidt. “Synthesis of a Structurally Defined Antigen-Immunostimulant Combination for use in Cancer Vaccines,” Chem. Eur. J. 1999, 5, 2432-2438.
Hawkins Lynn D.
Ishizaka Sally T.
Lewis Michael
McGuiness Pamela
Rose Jeffrey
Eisai Co. Ltd.
Hale and Dorr LLP
Lambkin Deborah C.
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