Therapeutic Agents For Treating Restless Leg Syndrome

Patent No. US11660279 (titled "Therapeutic Agents For Treating Restless Leg Syndrome") was filed by Intrabio Ltd on Feb 14, 2019.

’279 is related to the field of treatments for neurological disorders, specifically addressing Restless Legs Syndrome (RLS), also known as Willis-Ekbom disease. RLS is characterized by an irresistible urge to move the limbs, often accompanied by uncomfortable sensations, leading to sleep disturbances and reduced quality of life. Current treatments often involve dopamine agonists, which can have undesirable side effects like augmentation and impulse control disorders, creating a need for alternative therapeutic approaches.

The underlying idea behind ’279 is that administering leucine, acetyl-leucine, or a pharmaceutically acceptable salt thereof can effectively treat RLS and its associated symptoms. This insight stems from the observation that these compounds, particularly acetyl-leucine, have shown promise in treating vertigo and cerebellar ataxia, suggesting a potential neuroprotective or neuromodulatory effect that could alleviate RLS symptoms.

The claims of ’279 focus on methods of treating RLS or its symptoms by administering leucine, acetyl-leucine, or a pharmaceutically acceptable salt to a subject in need. The claims encompass both the use of these compounds to treat the overall syndrome and to specifically diminish, inhibit, or eliminate individual symptoms associated with RLS, such as lower leg sensations, periodic limb movements, and sleep disturbances.

In practice, the invention involves formulating leucine or acetyl-leucine into a pharmaceutical composition suitable for oral or other routes of administration. The dosage can be adjusted based on the severity of the RLS, the patient's characteristics, and the specific form of the compound used. The treatment aims to reduce the severity of RLS symptoms, as measured by scales like the International Restless Legs Syndrome Study Group Rating Scale (IRLS), improving the patient's overall well-being and quality of life.

The differentiation from prior approaches lies in the use of leucine and acetyl-leucine, which offer a potentially safer alternative to traditional dopamine-based treatments. While dopamine agonists can lead to augmentation and other side effects, leucine and acetyl-leucine may act through different mechanisms, possibly involving the vestibulo-cerebellum or other neural pathways, to alleviate RLS symptoms without the same risks. The case studies presented in the patent demonstrate a reduction in IRLS scores in patients treated with acetyl-DL-leucine, suggesting a tangible clinical benefit.

How does this patent fit in bigger picture?

Technical landscape at the time

In the late 2010s when ’279 was filed, at a time when pharmaceutical compositions were commonly administered orally or via injection, and when researchers commonly relied on rating scales to assess the severity of conditions.

Novelty and Inventive Step

The examiner approved the claims because they are novel and non-obvious over the combined teachings of Strupp et al. and Pedroso et al. While Strupp et al. teaches that acetyl-DL-leucine can improve symptoms of cerebellar ataxia, and Pedroso et al. teaches the occurrence of restless leg syndrome (RLS) in patients with cerebellar ataxias, the examiner stated that the combined teachings do not make obvious the claimed method of treating RLS by administering leucine, acetyl-leucine, or a pharmaceutically acceptable salt thereof. The examiner also noted that there is no evidence that a person having cerebellar ataxia treated with acetyl-DL-leucine necessarily had RLS. Additionally, the applicant's filing of terminal disclaimers over the co-pending applications overcomes the nonstatutory double patenting rejections.

Claims

This patent contains 18 claims, with claims 1 and 12 being independent. The independent claims are directed to methods of treating or diminishing symptoms of restless legs syndrome by administering leucine, acetyl-leucine, or a pharmaceutically acceptable salt thereof. The dependent claims generally specify aspects and embodiments of the methods, such as the type of RLS, effective amounts, and specific compounds.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)	Support for Specification	Interpretation
One or more symptoms (Claim 1, Claim 12)	“A “symptom” associated with RLS includes any clinical or laboratory manifestation associated with RLS. Symptoms of RLS are often, but need not be, manifestations associated with the disease that the subject can feel or observe. Symptoms associated with RLS include, but are not limited to, lower leg sensations, periodic limb movements of sleep (PLMS), unpleasant leg sensation, urge to move, restlessness, sleep disturbances, excessive daytime sleepiness and the like.”	Any clinical or laboratory manifestation associated with RLS, including manifestations that the subject can feel or observe.
Pharmaceutically acceptable salt (Claim 1, Claim 12)	“A “pharmaceutically acceptable salt” as referred to herein, is any salt preparation that is appropriate for use in a pharmaceutical application. Pharmaceutically acceptable salts include, but are not limited to, amine salts, such as N,N′-dibenzylethylenediamine, chloroprocaine, choline, ammonia, diethanolamine and other hydroxyalkylamines, ethylenediamine, N-methylglucamine, procaine, N-benzylphenethylamine, 1-para-chloro-benzyl-2-pyrrolidin-1′-ylmethylbenzimidazole, diethylamine and other alkylamines, piperazine, tris(hydroxymethyl)aminomethane and the like; alkali metal salts, such as lithium, potassium, sodium and the like; alkali earth metal salts, such as barium, calcium, magnesium and the like; transition metal salts, such as zinc, aluminum and the like; other metal salts, such as sodium hydrogen phosphate, disodium phosphate and the like; mineral acids, such as hydrochlorides, sulfates and the like; and salts of organic acids, such as acetates, lactates, malates, tartrates, citrates, ascorbates, succinates, butyrates, valerates, fumarates and the like.”	Any salt preparation of leucine or acetyl-leucine that is appropriate for use in a pharmaceutical application.
Restless legs syndrome (Claim 1, Claim 12)	“Restless legs syndrome (RLS), also known as Willis-Ekborn disease, is a neurological disorder reported to affect about 10% of adults with higher prevalence in women and older people. RLS is characterized by an overwhelming urge to move one's body, typically accompanied by uncomfortable or odd sensations. It most commonly affects the legs, particularly between the knee and ankle, but can affect other areas, such as the arms, torso, or even phantom limbs.”	A neurological disorder characterized by an overwhelming urge to move one's body, typically accompanied by uncomfortable or odd sensations, most commonly affecting the legs.
Subject in need thereof (Claim 1, Claim 12)	“A “subject in need thereof” as used herein may be any subject who has RLS or one or more symptoms associated with RLS, and may also include any subject or patient who is at risk or believed to be at risk of developing RLS or one or more symptoms associated with RLS. The subject may or may not have been diagnosed with RLS. For example, the subject may not yet have a diagnosis (clinical or otherwise) of RLS but may have one or more symptoms of RLS.”	Any subject who has RLS or one or more symptoms associated with RLS, and may also include any subject or patient who is at risk or believed to be at risk of developing RLS or one or more symptoms associated with RLS.
Therapeutically effective amount (Claim 12)	“A “therapeutically effective amount” of an agent is any amount which, when administered to a subject, is the amount of agent that is needed to produce the desired effect, which, for the present disclosure, can be therapeutic and/or prophylatic. The dose may be determined according to various parameters, such as the specific form of leucine or acetyl-leucine used; the age, weight and condition of the patient to be treated; the route of administration; and the required regimen.”	The amount of leucine, acetyl-leucine, or a pharmaceutically acceptable salt thereof needed to produce the desired therapeutic and/or prophylactic effect in a subject.

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US11660279

INTRABIO LTD

Application Number: US16968919
Filing Date: Feb 14, 2019
Status: Granted
Expiry Date: Sep 2, 2039
External Links: Slate, USPTO, Google Patents

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