Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-03-27
2003-04-15
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S011400, C514S012200, C514S885000
Reexamination Certificate
active
06548527
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to methods for treating immune-mediated ear disorders.
Immune mediated ear disorders, such as immune-mediated cochlear or vestibular disorders (IMCVD), continue to present a management challenge to the otolaryngologist. These disorders represent a syndrome of sensorineural hearing loss, often associated with vertigo, tinnitus, and aural fullness believed to be due to an autoimmune mechanism. The sequelae of IMCVDs include devastating disabilities, such as profound deafness and serious vestibular dysfunction. Immunosuppressive drugs like cyclophosphomide and anti-rheumatic agents like methotrexate are employed for IMCVD, but are associated with variable efficacy, slow onset of effects, and sometimes serious toxicity.
SUMMARY OF THE INVENTION
In general, the invention features a method of treating a mammal (for example, a human) with an immune-mediated ear disorder, the method involving administering to the mammal a therapeutically-effective amount of a TNF antagonist.
In preferred embodiments, the immune-mediated ear disorder is an immune-mediated cochlear or vestibular disorder (IMCVD); the immune-mediated ear disorder involves a hearing impairment; the immune-mediated ear disorder is autoimmune-mediated; or the immune-mediated ear disorder affects the inner ear. Preferably, the TNF antagonist is a TNF-&agr; antagonist or a TNF fusion protein. Particularly preferred TNF antagonists include etanercept and infliximab.
If desired, administration of the TNF antagonist may be accompanied by administration of a pyrimidine synthesis inhibitor (for example, leflunomide), a steroid, an anti-inflammatory compound, a cytotoxic compound, an anti-neoplastic metabolite, or a secondary anti-rheumatic agent (for example, methotrexate).
In a second aspect, the invention features a method of treating a mammal (for example, a human) with an immune-mediated ear disorder, the method involving administering to the mammal a therapeutically-effective amount of a pyrimidine synthesis inhibitor.
In preferred embodiments of this aspect, the immune-mediated ear disorder is an immune-mediated cochlear or vestibular disorder (IMCVD); the immune-mediated ear disorder involves a hearing impairment; the immune-mediated ear disorder is autoimmune-mediated; or the immune-mediated ear disorder affects the inner ear. A preferred pyrimidine synthesis inhibitor is leflunomide.
By “treating” is meant the medical management of a patient with the intent that a cure, amelioration, prevention, or stabilization of a disorder, associated disorder, associated pathological condition, or symptom will result. This term includes active treatment, that is, treatment directed specifically toward improvement of the disorder, associated disorder, or associated pathological condition, as well as causal treatment, that is, treatment directed toward removal of the cause of the disorder, associated disorder, or pathological condition. In addition, this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disorder, associated disorder, or associated pathological condition, or symptoms; preventative treatment, that is, treatment directed to prevention of the disorder or associated disease, pathological condition, or symptoms; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the disorder, associated disorder, pathological condition, or symptoms. The term “treating” also includes symptomatic treatment, that is, treatment directed toward constitutional symptoms of the disorder, associated disease, or pathological condition.
By “therapeutically-effective amount” is meant an amount sufficient to produce a healing, curative, ameliorative, or stabilizing effect either in the treatment of an immune-mediated ear disease or disorder, or in one or more of its symptoms.
By “immune-mediated ear disorder” or “immune-mediated ear disease” is meant any impairment of ear function that is brought about by an immune-based mechanism, such as an autoimmune or inflammatory response. Any portion of the ear may be affected, but the inner ear is most often compromised. Immune-mediated ear disorders include, without limitation, immune-mediated cochlear or vestibular disorders (IMCVD), immune-mediated Meniere's disease, autoimmune ear disease (AIED), Cogan's Syndrome, and Wegener's granulomatosis and rheumatoid conditions of the middle and outer ear (for example, arthritis of the ossicles and relapsing polychondritis). Symptoms related to immune-mediated ear disorders include, without limitation, hearing impairment (including full or partial hearing loss in one or both ears), vertigo, tinnitus, fullness in the ear, otalgia, otorrhea/chronicotitis media, and TM perforation.
By a “TNF antagonist” is meant any compound (for example, any protein) which reduces or inhibits the action of TNF. TNF antagonists may act by inhibiting TNF (for example, TNF-&agr;) or a TNF receptor (for example, the TNF-&agr; receptor). Any decrease in TNF action is considered useful in the invention; however, decreases of at least 10%, 25%, or even 40% or 50% relative to the level of TNF action measured for an untreated control are preferred.
By a “pyrimidine synthesis inhibitor” is meant any compound which reduces the level of pyrimidine synthesis. Any decrease in pyrimidine synthesis is considered useful in the invention; however, decreases of at least 10%, 25%, or even 40% or 50% relative to the level of pyrimidine synthesis measured for an untreated control are preferred.
The present invention provides a number of advantages. Importantly, it provides new therapeutics for the treatment of immune-mediated ear disorders, and particularly immune-mediated inner ear disorders, such as IMCVDs, and their associated symptoms, such as hearing impairments, vertigo, and tinnitus. In addition, the preferred compounds described herein, the TNF antagonists, etanercept or infliximab, and the pyrimidine synthesis inhibitor, leflunomide, are known to be well tolerated by humans. Moreover, etanercept is fast acting, an important advantage for disorders such as immune-mediated Meniere's disease where rapid therapeutic intervention is required.
Other features and advantages will be apparent from the following detailed description of the invention, and from the claims.
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Choi Hyon K.
Poe Dennis S.
Rahman Mahboob U.
Clark & Elbing LLP
Criares Theodore J.
Kim Jennifer
The General Hospital Corporation
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