Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-05-31
2004-03-02
Solola, Taofiq (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S365000, C514S374000, C514S414000, C514S415000, C548S202000, C548S235000, C548S466000, C546S277400
Reexamination Certificate
active
06699886
ABSTRACT:
BACKGROUND OF THE INVENTION
Inflammation represents a cascade of physiological and immunological reactions that nature has designed as the first cellular response to noxious stimuli in an effort to localize toxic materials or prevent tissue injury. Clinically, inflammation is a primary disease under acute conditions or is a manifestation of underlying pathophysiological abnormalities in chronic disease, characterized by classic signs of redness, pain, swelling and loss of function.
The inflammatory mediators IFN-gamma, IL-2, IL-4, IL-5, IL-8, and TNF-alpha have been implicated in the initiation and propagation of several inflammatory disorders. For example, IFN-gamma, which acts as a regulator of other pro-inflammatory cytokines, is the nexus of inflammation in autoimmune disorders such as multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), and rheumatoid arthritis (RA). Other IFN-gamma diseases include, vascular dementia, Alzheimer's disease, cellular and tissue damage seen in graft-versus-host disease, lupus, and the like. Furthermore, it has long been suspected that TNF-alpha serves as the primary cytokine orchestrating the inflammatory cascade of various debilitating diseases such as rheumatoid arthritis (RA), psoriasis, vasculitis, ischemic-reperfusion injury, and inflammatory bowel disease (IBD). In fact, anti-TNF antibodies and receptor decoys, i.e., Remicade and Enbrel have demonstrated efficacy in treating RA and IBD. Other TNF-alpha related diseases include, photo-aging, leprosy, Leishmania, cachexia, endotoxemia, etc. Other disorders mediated by IFN-gamma and/or TNF-alpha include inflammatory bowel diseases (ulcerative colitis and Crohn's disease), atopic dermatitis, irritant contact dermatitis, osteoarthritis, asthma, chronic pelvic pain, inflammatory muscle disease, allergic rhinitis, vaginitis, interstitial cystitis, conjunctivitis, gastritis, chronic fatigue syndrome, scleroderma, osteoporosis, and numerous other hyperproliferative, inflammatory and degenerative disorders.
Hyperproliferative and inflammatory mucocutaneous disorders affect millions of individuals in the United States every year. Such disorders range from mild to life threatening, and include, for example, skin cancer, atopic dermatitis, psoriasis, and asthma and inflammatory bowel disease due to inflammation of the intestine wall. In addition, extrinsic skin aging can be caused by chronic inflammation and insufficient repair due to repetitive exposures to environmental insults, e.g., ultraviolet radiation. Aging of skin and in particular extrinsic aging can lead to any of a number of skin conditions requiring treatment.
Eczema, also called eczematous dermatitis, is one example of a common inflammatory mucocutaneous disorder. Eczema is a red, itchy, non-contagious inflammation of the skin that may be acute or chronic, with red skin patches, pimples, crusts, or scabs occurring either alone or in combination. The skin may be dry, or it may discharge a watery fluid, resulting in an itching or burning sensation. The affected skin may become infected. The various causes of eczematous dermatitis are classified as either external (irritations, allergic reactions, exposure to certain microorganisms, or chemicals), congenital (inherited predisposition), and environmental (stress, heat, and the like). Eczema may clear for years, only to reappear later at a different site.
Eczema can come in any of several forms, including, most commonly, atopic dermatitis. Atopic dermatitis is very common in all parts of the world. This chronically relapsing inflammatory skin disorder affects about ten percent of infants and three percent of the U.S. population overall. The disease can occur at any age, but is most common in infants to young adults (see, Hanifin J M et al.,
Arch. Dermatol
., 135(12):1551, 2000). The face is often affected first, then the hands and feet. Sometimes dry red patches appear all over the body. In older children the skin folds are most often affected, especially the elbow creases and behind the knees. In adults the face and hands are more likely to be involved. The condition usually improves in childhood or sometime before the age of 25. Most people with atopic dermatitis have family members with similar problems. Severity of the disease can be evaluated by EASI (Eczema Area Severity Index) score (see, Hanifin J M,
Exp. Dermatol
., 10(1)11-18, 2001).
Another atopic disease, but which affects the lungs rather than the skin, is allergic asthma. Asthma is a chronic lung disease characterized by inflammation of the air passages (see, Busse W W, et al., “Asthma,”
New Engl. J. Med
., 344(5):350-362, 2001). This condition is estimated to affect about 15 million Americans and can be severe and result in death if not treated. A number of factors can exacerbate asthma including, e.g., rapid changes in temperature or humidity, allergies, upper respiratory infections, exercise, stress or smoking (cigarette). Typical treatments include bronchodilators which are given orally or delivered as an aerosol (inhaled), and, for the most difficult cases, corticosteroids. New, effective treatments without steroid-related side effects will be greatly welcome in this disease of increasing prevalence (see, Thomas P S, “Tumor Necrosis Factor-Alpha: The role of this multifunctional cytokine in asthma,”
Immunol. Cell Biol
. 79(2):132-140, 2001).
Another example of a mucocutaneous inflammatory disorder is allergic rhinitis (hay fever). Allergic rhinitis is caused by a nasal inflammation in response to an irritant or an allergen. This condition can be seasonal or occur throughout the year (perennial). Typically, allergic rhinitis is treated by the administration of antihistamines either orally or locally (e.g., using nasal sprays). Other examples of mucocutaneous inflammatory disorders include those that involve cornification. Examples of such disorders include lamellar ichthyosis, acne, and rosacea.
Papulosquamous disorders are those characterized, as the name suggests, by scaly papules and plaques. Some of the more common papulosquamous disorders include psoriasis and lichen planus, both of which are manifested by a local inflammation of either the skin or a mucosal tissue (e.g., in the case of oral lichen planus).
Psoriasis is a persistent skin disease that got its name from the Greek word for “itch”. The skin becomes inflamed, producing red, thickened areas with silvery scales, most often on the scalp, elbows, knees, and lower back. Severe psoriasis may cover large areas of the body. Psoriasis is not contagious, and has some genetic basis, as it is more likely to occur in people whose family members have it. In the United States about 2% of adults have psoriasis (four to five million people). Approximately 150,000 new cases occur each year. The cause of psoriasis is unknown. However, recent discoveries point to an abnormality in the functioning of key white cells in the blood stream triggering inflammation in the skin. Psoriasis is thus thought to be due, at least in part, to an abnormal immune reaction against some component of the skin. This leads to the local expression of cell adhesion molecules, up-regulation of inflammatory cytokines and growth factors, and to infiltration of inflammatory leukocytes into the tissue. As a result, the two hallmark features of psoriasis are local inflammation and epidermal hyperproliferation. The combination of hyperproliferation with incomplete terminal differentiation leads to the formation of a thickened stratum corneum or plaques.
In addition to psoriasis, other hyperproliferative skin disorders include, but are not limited to, basal cell carcinoma, squamous cell carcinoma (Bowen's disease), keratosis, such as actinic or seborrheic keratosis, and disorders of keratinization, such as ichthyosis and keratoderma. These hyperproliferative skin disorders result from the loss of the regulatory mechanisms that control the proliferation and differentiation of keratinocytes. Basal and squamous cell carcinomas are the most common forms of skin cancer. About
Baker Don R.
Parks Thomas P.
Cellegy Pharmaceuticals Inc.
Solola Taofiq
Townsend and Townsend / and Crew LLP
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