Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-09-29
2002-11-26
Henley, III, Raymond (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06486168
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to pharmaceutical formulations and methods for application of immunomodifying imidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amine, thiazolo- and oxazolo-quinolinamines and pyridinamines, imidazonaphthyridine and tetrahydroimidazonaphthyridine amines to a mucosal surface. In one embodiment, the invention provides formulations and methods which are particularly advantageous for topical application to the cervix for treatment of cervical conditions such as cervical dysplasias including dysplasia associated with human papillomavirus (HPV).
BACKGROUND
Many imidazoquinoline amine, imidazopyridine amine, 6,7-fused cycloalkylimidazopyridine amine, 1,2-bridged imidazoquinoline amine, thiazolo- and oxazolo-quinolinamines and pyridinamines, imidazonaphthyridine and tetrahydroimidazonaphthyridine amine compounds have demonstrated potent immunostimulating, antiviral and antitumor (including anticancer) activity, and have also been shown to be useful as vaccine adjuvants to enhance protective immune system response to vaccines. These compounds are hereinafter sometimes collectively referred to as the “IRM” (immune response modifier) compounds of the invention. Such compounds are disclosed in, for example, U.S. Pat. Nos. 4,689,338; 5,389,640, 5,268,376, 4,929,624, 5,266,575, 5,352,784, 5,494,916, 5,482,936, 5,346,905, 5,395,937, 5,238,944, 5,525,612, WO99/29693 and U.S. Ser. No. 09/361,544 wherein their immunostimulating, antiviral and antitumor activities are discussed in detail, and certain specific diseases are identified as being susceptible to treatment therewith, including basal cell carcinoma, eczema, essential thrombocythaemia, hepatitis B, multiple sclerosis, neoplastic diseases, psoriasis, rheumatoid arthritis, type I herpes simplex, type II herpes simplex, and warts. One of these IRM compounds, known as imiquimod, has been commercialized in a topical formulation, Aldara™, for the treatment of anogenital warts associated with human papillomavirus.
The mechanism for the antiviral and antitumor activity of these IRM compounds is thought to be due in substantial part to enhancement of the immune response due to induction of various important cytokines (e.g., interferons, interleukins, tumor necrosis factor, etc.). Such compounds have been shown to stimulate a rapid release of certain monocyte/macrophage-derived cytokines and are also capable of stimulating B cells to secrete antibodies which play an important role in these IRM compounds' antiviral and antitumor activities. One of the predominant immunostimulating responses to these compounds is the induction of interferon (IFN)-&agr; production, which is believed to be very important in the acute antiviral and antitumor activities seen. Moreover, up regulation of other cytokines such as, for example, tumor necrosis factor (TNF), IL-1 and IL-6 also have potentially beneficial activities and are believed to contribute to the antiviral and antitumor properties of these compounds.
Although some of the beneficial effects of IRM's are known, the ability to provide therapeutic benefit via topical application of an IRM for treatment of a particular condition at a particular location may be hindered due to tissue irritation, formulation wash away, poor permeation or undesired systemic delivery of the topically applied compound. Accordingly, there is a need for new methods and formulations to provide the greatest therapeutic benefit from this class of compounds.
SUMMARY OF THE INVENTION
It will be appreciated that at several locations throughout the specification, guidance is provided through lists of examples. In each instance, the recited list serves only as a representative group; it is not meant that the list is exclusive.
The present disclosure provides pharmaceutical formulations containing immune response modifier (“IRM”) compounds and methods for treatment of conditions associated with a mucosal surface. The methods and formulations of the invention may be particularly advantageous for treatment of cervical conditions such as cervical dysplasias including cervical intraepithelial neoplasia.
Particularly preferred IRM compounds suitable for the pharmaceutical formulations of the invention include 4-amino-2-ethoxymethyl-&agr;,&agr;-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol and 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (known as imiquimod).
The IRMs can be formulated for application to a mucosal membrane, particularly the cervical mucosa.
REFERENCES:
patent: 3314941 (1967-04-01), Littell et al.
patent: 3917624 (1975-11-01), El-Haj et al.
patent: 4689338 (1987-08-01), Gerster
patent: 4698348 (1987-10-01), Gerster
patent: 4929624 (1990-05-01), Gerster et al.
patent: 4988815 (1991-01-01), Andre et al.
patent: 5037986 (1991-08-01), Gerster
patent: 5175296 (1992-12-01), Gerster
patent: 5238944 (1993-08-01), Wick et al.
patent: 5266575 (1993-11-01), Gerster et al.
patent: 5268376 (1993-12-01), Gerster
patent: 5346905 (1994-09-01), Gerster
patent: 5352784 (1994-10-01), Nikolaides et al.
patent: 5367076 (1994-11-01), Gerster
patent: 5389640 (1995-02-01), Gerster et al.
patent: 5395937 (1995-03-01), Nikolaides et al.
patent: 5444065 (1995-08-01), Nikolaides et al.
patent: 5446153 (1995-08-01), Lindstrom et al.
patent: 5482936 (1996-01-01), Lindstrom
patent: 5494916 (1996-02-01), Lindstrom et al.
patent: 5525612 (1996-06-01), Gerster
patent: 5585612 (1996-12-01), Harp, Jr.
patent: 5605899 (1997-02-01), Gerster et al.
patent: 5627281 (1997-05-01), Nikolaides et al.
patent: 5644063 (1997-07-01), Lindstrom et al.
patent: 5648516 (1997-07-01), Nikolaides et al.
patent: 5714608 (1998-02-01), Gerster
patent: 5741908 (1998-04-01), Gerster et al.
patent: 5741909 (1998-04-01), Gerster et al.
patent: 5886006 (1999-03-01), Nikolaides et al.
patent: 5977366 (1999-11-01), Gerster et al.
patent: 6069149 (2000-05-01), Nanba et al.
patent: 6245776 (2001-06-01), Skwierczynski et al.
patent: 0 894 797 (1998-02-01), None
patent: 9-208584 (1997-08-01), None
patent: 93/09119 (1993-05-01), None
patent: 97/418884 (1997-11-01), None
patent: 97/48704 (1997-12-01), None
patent: 98/24436 (1998-06-01), None
patent: 99/29693 (1999-06-01), None
patent: 00/06577 (2000-02-01), None
patent: 00/09506 (2000-02-01), None
patent: 00/40228 (2000-07-01), None
Wozniak, et al, “The Amination of 3-nitro-1, 5-naphthyridines by Liquid Ammonia/Potassium Permanganate1,2. A New and Convenient Amination Method.”, Journal of the Royal Netherlands Chemical Society, 102, pp. 511-513, Dec. 12, 1983.
Brennan, et al, “Automated Bioassay of Interferons in Micro-test Plates”,Biotechniques,Jun./Jul., 78, 1983.
Testerman, et al, “Cytokine Induction by the Immunomodulators Imiquimod and S-27609”, Journal of Leukocyte Biology, vol. 58, pp. 365-372, Sep. 1995.
Bachman, et al, “Synthesis of Substituted Quinolylamines. Derivatives of 4-Amino-7-Chloroquinoline”, J. Org. Chem, 15, pp. 1278-1284 (1950).
Jain, et al, “Chemical and Pharmacological Investigations of Some &ohgr;-Substituted Alkylamino-3-aminopyridines”, J. Med. Chem., 11, pp. 87-92 (1968).
Baranov, et al., Chem. Abs. 85, 94371, (1976).
Berényi, et al, “Ring Transformation of Condensed Dihydro-as-triazines”,J. Heterocyclic Chem.,18, pp. 1537-1540 (1981).
R. Snoeck, G. Andrei and E. De Clercq, “Specific Therapies for Human Papilloma Virus Infections”, Current Opionion in Infectious Diseases, 1998, vol. 11, pp. 733-737.
“3M Pharmaceuticals unveils research and development and expansion plans” retrieved from STN International, No. 2138, p. 10-. . . (1996).
Harrison, C.J. et al, “Effects of Cytokines and R-837 a Cytokine Inducer on UV-Irradiation Augmented Recurrent Genital Herpes in Guinea-Pigs”,Antiviral Research,1991, vol. 15, No. 4, pp. 315-322.
Harrison, C.J. et al, “Modification of Immunological Responses and Clinical Disease During Topical R-837 treatment of Genital HSV-2 Infection”,Antiviral Research,1988, vol. 10, No. 4-5, pp. 209-224.
Miller, R.L. et al., Review Article. I
Busch Terri F.
Jozwiakowski Michael J.
Li Zheng Jane
Miller Richard L.
Phares Kenneth R.
3M Innovative Properties Company
Henley III Raymond
Howard MarySusan
Ringsred Ted K.
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