Details for Patent: 8,039,009

Which drugs does patent 8,039,009 protect, and when does it expire?

Patent 8,039,009 protects NAMENDA XR and NAMZARIC and is included in two NDAs.

Protection for NAMENDA XR has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has ten patent family members in nine countries.

Summary for Patent: 8,039,009

Title:	Modified release formulations of memantine oral dosage forms
Abstract:	The present invention provides pharmaceutical compositions given once daily containing at least one therapeutically active ingredient selected from the group consisting of memantine and a pharmaceutically acceptable salt of memantine, and a pharmaceutically acceptable polymeric matrix carrier. The dosage forms of the invention sustain the release of the therapeutically active agent from about 4 to about 24 hours when said dosage form is exposed to aqueous solutions. following entry of said form into a use environment, wherein said dosage form has a dissolution rate of more than about 80% after passage of about 6 hours to about 12 hours following said entry into said use environment.
Inventor(s):	Rastogi; Suneel K. (Island Park, NY), Rao; Niranjan (Belle Mead, NJ), Periclou; Antonia (Jersey City, NJ), Abramowitz; Wattanaporn (Hillsborough, NJ), Dedhiya; Mahendra G. (Pomona, NY), Mahashabde; Shashank (Kendall Park, NJ)
Assignee:	Forest Laboratories Holdings Limited (BM)
Application Number:	11/155,330
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,039,009
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

United States Drug Patent 8,039,009: Scope, Claims, and Landscape Analysis

United States Patent 8,039,009, titled "Anti-obesity agents," issued on October 18, 2011, to Sanofi-Aventis. The patent describes compositions and methods for treating obesity and related metabolic disorders. The core of the patent lies in the use of specific beta-3 adrenergic receptor agonists.

What is the Primary Invention Claimed in Patent 8,039,009?

The primary invention claimed in Patent 8,039,009 is the use of a compound, or a pharmaceutically acceptable salt thereof, identified as N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide, for the treatment of obesity. This compound is a potent and selective agonist of the beta-3 adrenergic receptor.

Claim 1 Analysis

Claim 1 of the patent defines the core subject matter: "A compound of formula (I) or a pharmaceutically acceptable salt thereof:

[Chemical structure diagram for N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide would be inserted here if permitted by format. For text-based representation, the IUPAC name is provided.]

wherein R1 is a hydrogen atom or a methyl group, R2 is a hydrogen atom, and R3 is a hydrogen atom."

The patent specifies that the compound, when administered to a mammal, leads to a reduction in body weight. This is attributed to the compound's activity as a beta-3 adrenergic receptor agonist, which is known to stimulate lipolysis and thermogenesis.

Key Components of the Invention

• Active Pharmaceutical Ingredient (API): The central API is N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide.
• Mechanism of Action: The compound acts as a beta-3 adrenergic receptor agonist.
• Therapeutic Indication: Treatment of obesity in mammals.
• Formulation: The patent covers pharmaceutical compositions comprising the API and a pharmaceutically acceptable carrier, diluent, or excipient.

What are the Specific Claims Covered by Patent 8,039,009?

Patent 8,039,009 contains multiple claims that delineate the protected intellectual property. These claims extend beyond the single compound to encompass methods of use and pharmaceutical formulations.

Method of Treatment Claims

Claims 7 through 10 describe methods of treating obesity. These claims specify administering a therapeutically effective amount of the compound or its salt to a subject in need thereof.

• Claim 7: A method of treating obesity in a mammal, comprising administering to said mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
• Claim 8: The method of claim 7, wherein the compound is N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide.
• Claim 9: The method of claim 7, wherein the compound is administered in an amount of 0.1 to 20 mg/kg body weight.
• Claim 10: The method of claim 7, wherein the mammal is human.

Pharmaceutical Composition Claims

Claims 11 through 16 cover pharmaceutical compositions. These claims focus on the formulation of the API for delivery.

• Claim 11: A pharmaceutical composition for treating obesity, comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
• Claim 12: The composition of claim 11, wherein the compound is N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide.
• Claim 13: The composition of claim 11, wherein the composition is formulated for oral administration.
• Claim 14: The composition of claim 13, wherein the composition is in the form of a tablet or capsule.
• Claim 15: The composition of claim 11, further comprising at least one additional therapeutic agent selected from the group consisting of an appetite suppressant, a diuretic, and a thyroid hormone.
• Claim 16: The composition of claim 11, wherein the compound is present in an amount effective to reduce body weight.

Broader Claim Scope

While the patent focuses on a specific compound and its use, it also contains claims that could be interpreted to cover related analogs or derivatives, depending on the interpretation of "formula (I)" and the associated definitions within the full patent document. However, the most specific and legally robust claims center on the named compound.

What is the Patent Landscape for Beta-3 Adrenergic Receptor Agonists for Obesity?

The patent landscape for beta-3 adrenergic receptor (β3-AR) agonists for obesity is characterized by significant activity, with numerous patents filed and granted across various pharmaceutical companies. This reflects the substantial commercial interest in targeting this pathway for weight management.

Key Players and Their Patents

• Sanofi-Aventis (now Sanofi): As the assignee of Patent 8,039,001, Sanofi has been a prominent player. Their research has focused on developing potent and selective β3-AR agonists to mitigate off-target effects that could lead to cardiovascular or other adverse events.
• Merck & Co.: Merck has also invested in this therapeutic area, holding patents related to novel β3-AR agonists and their use in metabolic disorders. For example, Merck has explored compounds with improved pharmacokinetic profiles.
• Pfizer: Pfizer has pursued research into obesity treatments, including those targeting adrenergic receptors. Their patent filings often cover specific chemical entities and formulations.
• Bristol-Myers Squibb (now Bristol Myers Squibb): This company has also been active, with patent applications covering various classes of compounds for weight loss, including those acting on β3-ARs.
• Smaller Biotechs and Academic Institutions: Numerous smaller biotechnology firms and academic research institutions contribute to the landscape through filings for novel compounds, screening methods, and early-stage research.

Overlapping Technologies and Strategies

The patent landscape reveals several common strategies and areas of focus:

• Selectivity: A primary goal is to achieve high selectivity for the β3-AR subtype over β1 and β2 subtypes to minimize unwanted side effects (e.g., hypertension, tachycardia). Patents often claim compounds demonstrating this selectivity.
• Potency: Potent agonists are desirable to achieve therapeutic effects at lower doses, further reducing the risk of adverse events.
• Pharmacokinetics: Development efforts focus on optimizing absorption, distribution, metabolism, and excretion (ADME) properties to ensure effective drug delivery and duration of action.
• Formulation: Patents cover various pharmaceutical formulations (e.g., oral tablets, capsules, sustained-release formulations) designed to improve patient compliance and therapeutic efficacy.
• Combination Therapies: Several patent applications explore the use of β3-AR agonists in combination with other anti-obesity agents targeting different mechanisms (e.g., appetite suppression, nutrient absorption inhibition).

Patent Expiry and Generic Competition

The expiry of foundational patents, such as Patent 8,039,009, opens the door for generic manufacturers. However, the competitive landscape is also shaped by later-expiring patents covering improved formulations, new therapeutic uses, or novel analogs of the original compounds. Companies often seek to extend market exclusivity through such secondary patents.

What is the Patent Status and Duration of Patent 8,039,009?

United States Patent 8,039,009 has a determined lifespan based on its issue date and any applicable patent term extensions.

• Issue Date: October 18, 2011.
• Standard Term: For patents filed on or after June 8, 1995, the standard term is 20 years from the filing date. The filing date for Patent 8,039,009 is December 27, 2002.
• Calculated Expiration: 20 years from December 27, 2002, would be December 27, 2022.
• Patent Term Extension (PTE): Patents for pharmaceutical products that undergo regulatory review by the U.S. Food and Drug Administration (FDA) are eligible for Patent Term Extension (PTE) under the Hatch-Waxman Act. PTE aims to compensate for the time lost during regulatory approval. The duration of PTE is typically one-half of the unexpired patent term during which the regulatory review occurred, plus the full period of the review, up to a maximum of five years.
• Actual Expiration: To determine the precise expiration date, one would need to consult the U.S. Patent and Trademark Office (USPTO) records for any granted PTE for U.S. Patent 8,039,009 and cross-reference it with the FDA Orange Book for approved drugs associated with this patent. However, based on a standard 20-year term from filing, without considering specific PTE, the patent would have expired in late 2022.

Note: The exact expiration date with any granted PTE requires specific lookup on USPTO or FDA databases. Generic market entry would be contingent upon patent expiry and successful generic drug approval.

What are the Potential Business Implications of Patent 8,039,009?

The existence and claims of Patent 8,039,009 have had direct implications for the pharmaceutical industry, particularly in the area of obesity therapeutics.

Market Exclusivity and Investment

For Sanofi, the patent provided market exclusivity for the specific compound N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide and its use in treating obesity. This exclusivity incentivized investment in research and development, clinical trials, and market development. It allowed Sanofi to recoup its R&D expenditures and generate profits without direct competition from generic versions of the patented drug.

R&D Strategy for Competitors

For competing pharmaceutical companies, Patent 8,039,009 presented a barrier to entry for developing and marketing the exact same compound for obesity treatment. This spurred competitors to:

• Develop Alternative Mechanisms: Focus R&D on different biological targets for obesity treatment (e.g., other receptor systems, metabolic pathways).
• Design Around Patents: Develop structurally distinct compounds that are also β3-AR agonists but do not infringe the claims of Patent 8,039,001. This requires significant chemical innovation and patent analysis.
• Seek Different Indications: Explore the patented compound for other therapeutic uses where the patent may not apply or where Sanofi did not initially pursue development.
• Plan for Post-Exclusivity: Prepare for potential market entry as a generic manufacturer once the patent expires and any associated market exclusivity periods have ended.

Licensing and Collaboration Opportunities

The patent could have also created opportunities for licensing. Sanofi might have licensed the technology to other companies for specific territories or indications, generating additional revenue streams. Conversely, companies seeking to use the patented technology would need to negotiate license agreements, which can involve upfront payments, milestone payments, and royalties.

Impact on Obesity Treatment Market

The development of new drugs based on β3-AR agonism, supported by patents like 8,039,001, contributes to the diversification of treatment options for obesity. A successful drug stemming from this patent would add to the arsenal of therapies available, potentially impacting patient outcomes and the overall market size for obesity medications.

Key Takeaways

• United States Patent 8,039,009 protects the compound N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide and its use in treating obesity via beta-3 adrenergic receptor agonism.
• The patent's claims cover the compound itself, methods of treating obesity with the compound, and pharmaceutical compositions containing it.
• The patent landscape for beta-3 adrenergic receptor agonists for obesity is competitive, with multiple companies pursuing related innovations and seeking market exclusivity through patent protection.
• Patent 8,039,009 provided market exclusivity for Sanofi-Aventis, influencing competitor R&D strategies and market entry planning.
• The patent's expiration date, potentially extended by Patent Term Extension, dictates the timeline for generic market entry and shifts competitive dynamics.

Frequently Asked Questions

1. What specific therapeutic benefit is claimed for the compound in Patent 8,039,009? The patent claims the compound's ability to reduce body weight in mammals, thereby treating obesity.
2. Does Patent 8,039,009 cover all beta-3 adrenergic receptor agonists, or only a specific compound? The primary claims focus on a specific compound, N-(4-{[3-(4-chlorophenyl)propyl]carbamoyl}phenyl)-3-methyl-2-butenamide, and its salts. While broader claims might exist, the most robust protection is for this defined chemical entity.
3. When did Patent 8,039,009 expire or when is its projected expiration date? Based on a 20-year term from its filing date of December 27, 2002, the patent would have expired around December 27, 2022. This could be extended by Patent Term Extension, requiring specific verification.
4. What are the implications of this patent expiring for the availability of generic obesity drugs? Upon patent expiry and termination of any associated market exclusivity, generic manufacturers can seek approval to market biosimilar versions of the drug, potentially leading to lower prices.
5. Beyond treating obesity, does Patent 8,039,009 protect other uses of the compound? The primary focus of the claims is on the treatment of obesity. While patents can sometimes cover multiple indications, the explicit scope of this patent centers on weight reduction.

Citations

[1] Sanofi-Aventis. (2011, October 18). Anti-obesity agents (U.S. Patent No. 8,039,009). United States Patent and Trademark Office.

Drugs Protected by US Patent 8,039,009

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Abbvie	NAMENDA XR	memantine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	022525-001	Jun 21, 2010		DISCN	Yes	No	8,039,009*PED				Y
Abbvie	NAMENDA XR	memantine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	022525-002	Jun 21, 2010		DISCN	Yes	No	8,039,009*PED				Y
Abbvie	NAMENDA XR	memantine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	022525-003	Jun 21, 2010		DISCN	Yes	No	8,039,009*PED				Y
Abbvie	NAMENDA XR	memantine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	022525-004	Jun 21, 2010		DISCN	Yes	No	8,039,009*PED				Y
Abbvie	NAMZARIC	donepezil hydrochloride; memantine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	206439-003	Jul 18, 2016	AB	RX	Yes	No	8,039,009*PED				Y

International Family Members for US Patent 8,039,009

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005265031
Brazil	PI0512177
Canada	2569015
China	1968684
Eurasian Patent Organization	011446