Comprehensive pharmacologic therapy for treatment of obesity including cysteine

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FOREIGN PATENT DOCUMENTS

EP GB JP WO

0347066 2137493 410067663 A 01/26642

12/1989 10/1984 3/1998 4/2001

OTHER PUBLICATIONS

Heath, "Pulmonary Vascular Disease" Medical Clinics of North

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for the antidepressant citalopram in brain microvessal endothelium;

written by B. Rochat, P. Baumann, KL Andus.

(Continued) Primary Examiner—Vickie Kim

(7'4) Attorney, Agent, or Firm—Patterson, Thuente, Skaar & Christensen, PA.

The comprehensive pharmacologic therapy for treatment of obesity including Cysteine is a procedure which involves the administration of a desired therapeutic range of Diethylpropion and/or Phentermine in combination with a SSRI medication and nutritional supplementation for brief and long durations which may be 12 months or more. The preferred procedure involves the administration of drugs in combination which are identified as: Citalopram (Celexa) and Phentermine; Citalopram (Celexa) and Diethylpropion; Citalopram (Celexa), Phentermine, and Diethylpropion. In addition nutritional supplementation such as a multivitamin, 5-Hydroxytryptophan, Cysteine, vitamin B6, vitamin C, Tyrosine, Calcium, and Lysine may be used to enhance the performance of the weight loss treatment program.

18 Claims, 1 Drawing Sheet

OTHER PUBLICATIONS

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Archives of Internal Medicine, Jan. 12, 1998, vol. 158, p. 102; Asymptomatic Mitral and Aortic Valve Disease Is Seen in Half of the Patients Taking 'Phen-Fen'; written by Griffen et al. The Medical Letter® On Drugs and Therapeutics, vol. 36 (Issue 936), Nov. 25, 1994, pp. 107-108; Fluoxetine (Prozac) and Other Drugs for Treatment of Obesity.

Archives of Internal Medicine, May 11, 1998, vol. 158, pp. 12781279; The "Phen-Pro" Diet Drug Combination is Not Associated With Valvular Heart Disease; written by Griffen et al. Deposition Transcripts of Dr. Martin C. Hinz (vol. I of Nov. 17, 2004; and vol. II of Feb. 24. 2005).

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* cited by examiner

1

COMPREHENSIVE PHARMACOLOGIC
THERAPY FOR TREATMENT OF OBESITY
INCLUDING CYSTEINE

This application is a Divisional Application from application Ser. No. 09/947,941, filed Sep. 6, 2001 which will issue on Jul. 6, 2004, as U.S. Pat. No. 6,759,437, which application is a Continuation-In-Part Patent Application of application Ser. No. 09/412,701 filed Oct. 4, 1999, which issued as U.S. Pat. No. 6,403,657 on Jun. 11, 2002, the entire contents of which are hereby incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

Research has identified that long term use of medications for treatment of obesity in patients has resulted in many problems. The two most significant problems encountered by patients using medications to assist in weight loss, assuming the absence of irreversible side effects from the medications, are that:

The medications stop working during therapy where at least 40% to 50% of patients quit losing weight (plateau) on an average of 3.3 months into therapy; and 5% to 8% of patients who receive drug therapy for weight problems experience the complication where the medications fail to assist in appetite suppression where the patient therefore does not lose significant weight.

In the past long term treatment, defined as treatment longer than 3 months to many years, with medications, has raised safety issues including, medication intolerability by the patient, medication side effects and most important ineffectiveness of the drugs or the cessation of benefit of the drugs which in turn causes the patient to fall out of appetite suppression and terminate weight loss.

A weight loss procedure using SSRI medication is disclosed in U.S. Pat. No. 5,795,895. The potential for patients to obtain goal weight loss under the process of U.S. Pat. No. 5,795,895 is low, and the failure of the drugs to provide a desired level of performance is at the heart of the problem.

In the past obesity or weight management procedures, as noted in U.S. Pat. No. 5,795,895, implement a single dosing

2

medications have unique chemical properties making the outcome of treatment of patients uncertain. In addition not all medications function to assist in weight loss. In the past SSRI (selective Serotonin Reuptake Inhibitor) medications

5 which have been used in weight loss include Fluoxetine Hydrochloride (Prozac), Sertraline (Zoloft), Fluvoxamine Maleate (Luvox), and Trazodone Hydrochloride (Desyrel).

The treatment programs for obesity as known also teach away from the use of alternative dosing procedures to

10 effectuate weight loss. Specifically U.S. Pat. No. 5,795,895 teaches that an SSRI medication never needs to be raised to improve the anorexiant effect of weight loss and that the SSRI medication level administered to a patient may be raised to assist in the treatment of coexisting conditions such

15 as depression.

It is therefore desirable to have a weight loss treatment program for a patient which provides for an effective therapeutic range of available medication to enhance desired weight loss. It is also desirable to provide a weight loss program which minimizes the percent of individuals who do not initially respond to the medication treatment regime or who cease to continue to receive the beneficial effects of the weight loss program following the initiation of the medication treatment due to nutritional deficiencies. These and

25

other problems are solved by the disclosed Comprehensive Pharmacologic Therapy For Treatment Of Obesity.

A problem has been known in the past where drugs which work on norepinephrine stop working after a period of time

30 when used in treating patients for weight loss. As stated in Wurtman et. al in U.S. Pat. No. 4,885,312.

Indirect-acting sympathomimetic amines (such as Phentermine) function by releasing stored norepinephrine from sympathetic nerve endings. The major problem with their

35 use is that after a few doses, they often stop functioning, i.e., tachyphylaxis sets in. Tachyphylaxis is known to be associated with partial depletion of the norepinephrine in the nerve endings, leading to the supposition that there are releasable and non-releasable pools of norepinephrine and

40 that when the drugs cease functioning, it is because the releasable pools have been severely depleted. The chemical pathway involved is:

Dopa, doparnuie, norepinephrine, and epinephrine are known as "catecholamines". Chemically the enzyme "Tyrosine Hydroxylase" limits the rate of formation of catecholamines. Another problem as known is to identify a way to increase the amounts of Tyrosine Hydroxylase or it's activity in a patient receiving treatment for obesity. No procedure is known which uses a dietary precursor approach to increase amounts of Tyrosine Hydroxylase and it's activity in a patient receiving treatment for obesity. No procedure is known to increase catecholamine levels in a patient by providing the precursor needed for the formation of Tyrosine Hydroxylase.

Catecholamine formation is regulated by a feed back loop involving norepinephrine and Tyrosine Hydroxylase. In this loop norepinephrine binds to each of the four legs of the