Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-07-27
2003-09-30
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S455000, C514S456000, C514S459000, C514S601000
Reexamination Certificate
active
06627653
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is directed to anticonvulsant derivatives useful in the treatment of depression, specifically unipolar depression, treatment-refractory depression, resistant depression, anxious depression and dysthymia. The present invention is further directed to the treatment of depression comprising administration of one or more anticonvulsant derivatives in combination with one or more compounds selected from mono-amine oxidase inhibitors, tricyclics, serotonin reuptake inhibitors, serotonin noradrenergic reuptake inhibitors, noradrenergic and specific serotonergic agents, noradrenaline reuptake inhibitors, natural products, dietary supplements, neuropeptides, compounds targeting neuropeptide receptors or hormones.
Compounds of Formula I:
are structurally novel antiepileptic compounds that are highly effective anticonvulsants in animal tests (MARYANOFF, B. E, NORTEY, S. O., GARDOCKI, J. F., SHANK, R. P. AND DODGSON, S. P.
J. Med. Chem.
1987, 30, 880-887; MARYANOFF, B. E., COSTANZO, M. J., SHANK, R. P., SCHUPSKY, J. J., ORTEGON, M. E., AND VAUGHT J. L.
Bioorg. Med. Chem. Lett.
1993, 3, 2653-2656; SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., MARYANOFF, B. E. Epilepsia 1994, 35, 450-460; MARYANOFF B E, COSTANZO M J, NORTEY S O, GRECO M N, SHANK R P, SCHUPSKY J J, ORTEGON M P, VAUGHT J L.
J. Med. Chem.
1998, 41, 1315-1343). These compounds are covered by three U.S. Pat. Nos.: 4,513,006, 5,242,942, and 5,384,327. One of these compounds 2,3:4,5-bis-O-(1-methylethylidene)-&bgr;-D-fructopyranose sulfamate, known as topiramate, has been demonstrated in clinical trials of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating simple and complex partial seizures and secondarily generalized seizures (E. FAUGHT, B. J. WILDER, R. E. RAMSEY, R. A. REIFE, L D. KRAMER, G. W. PLEDGER, R. M. KARIM et. al.,
Epilepsia
1995, 36 (S4), 33; S. K. SACHDEO, R. C. SACHDEO, R. A. REIFE, P. LIM and G. PLEDGER,
Epilepsia
1995, 36 (S4), 33; T. A. GLAUSER,
Epilepsia
1999, 40 (S5), S71-80; R. C. SACHDEO, Clin. Pharmacokinet. 1998, 34, 335-346), and is currently marketed for the treatment of seizures in patients with simple and complex partial epilepsy and seizures in patients with primary or secondary generalized seizures in the United States, Europe and most other markets throughout the world.
Compounds of Formula I were initially found to possess anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice (SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., and MARYANOFF, B. E.,
Epilepsia
1994, 35, 450-460). Subsequent studies revealed that Compounds of Formula I were also highly effective in the MES test in rats. Topiramate was also found to effectively block seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMURA, T. KANDA, A. ISHII, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M. SASA,
Eur. J. Pharmacol.
1994, 254, 83-89), and in an animal model of kindled epilepsy (A. WAUQUIER and S. ZHOU,
Epilepsy Res.
1996, 24, 73-77).
Compounds of formula I have further been found to be effective in the treatment of manic depressive bipolar disorder (Shank, U.S. Pat. No. 5,753,693).
Tollefson et al in WIPO Publication WO99/62522 disclose a method for the treatment of bipolar disease, bipolar depression or unipolar depression comprising administration of an atypical antipsychotic in combination with a compound selected from the group consisting of serotonin reuptake inhibitors, anticonvulsants and lithium.
Unipolar depression is defined as depressed mood on a daily basis for a minimum duration of two weeks. An episode may be characterized by sadness, indifference or apathy, or irritability and is usually associated with a change in a number of neurovegetative functions, including sleep patterns, appetite and body weight, motor agitation or retardation, fatigue, impairment in concentration and decision making, feelings of shame or guilt, and thoughts of death or dying (
Harrison's Principles of Internal Medicine,
2000). The criteria for a major depressive episode includes five or more symptoms present during the same 2-week period, where this represents a change from previous functioning; and where at least one of the symptoms is either depressed mood or loss of interest or pleasure. Symptoms of a depressive episode include depressed mood; markedly diminished interest or pleasure in all, or almost all, activities most of the day; weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day; insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt nearly every day; diminished ability to think or concentrate, or indecisiveness, nearly every day; recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. Further, the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. (
Diagnostic and Statistical Manual of Mental Disorders,
4
th
Edition, American Psychiatric Association, 1994).
Current treatment options for unipolar depression include monotherapy or combination therapy with various classes of drugs including mono-amine oxidase inhibitors, tricyclics, serotonin reuptake inhibitors, serotonin noradrenergic reuptake inhibitors, noradrenergic and specific serotonergic agents, noradrenaline reuptake inhibitor, “natural products” (such as Kava-Kava, St. John's Wort), dietary supplement (such as s-adenosylmethionine) and others. More specifically, drugs used in the treatment of depression include, but are not limited to imipramine, amitriptyline, desipramine, nortriptyline, doxepin, protriptyline, trimipramine, maprotiline, amoxapine, trazodone, bupropion, chlomipramine, fluoxetine, citalopram, sertraline, paroxetine, fluvoxamine, nefazadone, venlafaxine, reboxetine, mirtazapine, phenelzine, tranylcypromine, and/or moclobemide (eg, J. M. KENT,
Lancet
2000, 355, 911-918; J. W. WILLIAMS JR, C. D. MULROW, E. CHIQUETTE, P. H. NOEL, C. AGUILAR, and J. CORNELL,
Ann. Intern. Med.
2000, 132, 743-756; P. J. AMBROSINI,
Psychiatr. Serv.
2000, 51, 627-633). Several of these agents including, but not limited to, serotonin reuptake inhibitors are also used when depression and anxiety co-exist, such as in anxious depression (R. B. LYDIARD and O. BRAWMAN-MINTZER,
J. Clin. Psychiatry
1998, 59, Suppl. 18, 10-17; F. ROUILLON,
Eur. Neuropsychopharmacol.
1999, 9 Suppl. 3, S87-S92).
In the clinic, 40-50% of depressed patients who are initially prescribed antidepressant therapy do not experience a timely remission of depression symptoms. This group typifies treatment-refractory depression, that is, a failure to demonstrate an “adequate” response to an “adequate” treatment trial (that is, sufficient intensity of treatment for sufficient duration) (R. M. BERMAN, M. NARASIMHAN, and D. S. CHARNEY,
Depress. Anxiety
1997, 5, 154-164). Moreover, about 20-30% of depressed patients remain partially or totally resistant to pharmacological treatment including combination treatments (J. ANANTH,
Psychother. Psychosom.
1998, 67, 61-70; R. J. CADIEUX,
Am. Fam. Physician
1998, 58, 2059-2062). Increasingly, treatment of resistant depression includes augmentation strategies including treatment with pharmacological agents such as, lithium, carbamazepine, and triiodothyronine, and the like (M. HATZINGER and E. HOLSBOER-TRACHSLER,
Wien. Med. Wochenschr.
1999, 149, 511-514; C. B. NEMEROFF,
Depress. Anxiety
1996-1997, 4, 169-181; T. A. KETTER, R. M. POST, P. I. PAREKH and K. WORTHINGTON,
J. Clin. Psychiatry
1995, 56, 471-475; R. T. JOFFE, W. SINGER, A. J. LEVITT, C. MACDONALD,
Arch. Gen. Psychiatry
1993, 50, 397-393).
Dysthymia is
Bacaltchuk Josue
Plata-Salaman Carlos R.
Prado-Lima Pedro A. S.
Fay Zohreh
Kwon Brian-Yong S.
Ortho-McNeil Pharmaceutical , Inc.
Palo Ralph R.
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