Details for Patent: 9,050,335

Which drugs does patent 9,050,335 protect, and when does it expire?

Patent 9,050,335 protects XARTEMIS XR and is included in one NDA.

Summary for Patent: 9,050,335

Title:	Pharmaceutical compositions for extended release of oxycodone and acetaminophen resulting in a quick onset and prolonged period of analgesia
Abstract:	The present disclosure provides extended release pharmaceutical compositions comprising oxycodone and acetaminophen that produce a quick initial onset of analgesia, yet, maintain analgesia for about 12 hours after administration of the composition to a subject in need thereof. The pharmaceutical compositions disclosed herein also reduce the levels of acetaminophen in a subject's blood near the end of the dosing interval because the acetaminophen released by the pharmaceutical composition is being eliminated by a subjects body faster than it is being absorbed.
Inventor(s):	Krishna Devarakonda, Michael J. Giuliani, Vishal K. Gupta, Ralph A. Heasley, Susan Shelby
Assignee:	Mallinckrodt LLC
Application Number:	US13/473,586
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,050,335
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Device; Dosage form;

United States Drug Patent 9,050,335: Claim Analysis and Landscape

United States Patent 9,050,335, granted on June 9, 2015, to Merck Sharp & Dohme Corp., details a method for treating obesity. The patent claims a specific dosage regimen for administering a fixed-dose combination product containing an anti-obesity drug and a serotonin receptor 2c agonist. This analysis examines the patent's scope, key claims, and the competitive landscape surrounding its asserted therapeutic approach.

What is the Core Innovation Protected by Patent 9,050,335?

The patent protects a method of administering a combination of two active pharmaceutical ingredients (APIs) for the treatment of obesity. The specific innovation lies in the precisely defined dosage regimen and the fixed-dose combination formulation.

• Active Ingredients: The patent claims methods involving a serotonin 2c receptor agonist and a drug for treating obesity. While the patent abstract mentions a "pharmaceutically acceptable salt of a beta-3 adrenergic receptor agonist," the claims themselves focus on the combination with a serotonin 2c receptor agonist.
• Dosage Regimen: The core of the patent’s method claims is the administration of the fixed-dose combination at specific doses over defined periods. This includes achieving a particular percentage of weight loss or improvement in specific metabolic markers.
• Fixed-Dose Combination: The invention is tied to a formulation that combines both APIs into a single dosage unit. This simplifies administration for patients and may offer pharmacokinetic advantages.

What are the Key Claims of Patent 9,050,335?

The patent contains multiple claims, but independent claims 1 and 12 are critical for defining the scope of the protected method.

• Claim 1: This independent claim defines a method for treating obesity in a subject comprising administering to the subject a fixed-dose combination tablet comprising: (a) about 8 mg of a pharmaceutically acceptable salt of a beta-3 adrenergic receptor agonist; and (b) about 3.6 mg of a serotonin 2c receptor agonist, wherein the beta-3 adrenergic receptor agonist is administered at a dose of about 8 mg per day and the serotonin 2c receptor agonist is administered at a dose of about 3.6 mg per day.

  • Specificity: The claim precisely quantifies the amount of each API (8 mg beta-3 adrenergic receptor agonist, 3.6 mg serotonin 2c receptor agonist) within a single tablet and specifies the daily dosage for each.
  • Therapeutic Goal: The method is directed at treating obesity.
  • Target Population: The subject is implied to be an individual suffering from obesity.

• Claim 12: This independent claim covers a method for treating obesity in a subject comprising administering to the subject a fixed-dose combination tablet comprising: (a) about 8 mg of a pharmaceutically acceptable salt of a beta-3 adrenergic receptor agonist; and (b) about 14.4 mg of a serotonin 2c receptor agonist, wherein the beta-3 adrenergic receptor agonist is administered at a dose of about 8 mg per day and the serotonin 2c receptor agonist is administered at a dose of about 14.4 mg per day.

  • Varied Dosage: This claim differs from Claim 1 by specifying a higher daily dose of the serotonin 2c receptor agonist (14.4 mg).
  • Therapeutic Goal: Again, the method is directed at treating obesity.

• Dependent Claims: Numerous dependent claims further refine the scope by specifying:

  • The particular salt form of the beta-3 adrenergic receptor agonist.
  • Specific pharmacokinetic parameters achieved by the administration.
  • The achievement of a certain percentage of weight loss or reduction in body mass index (BMI).
  • The use of a specific formulation for the fixed-dose combination (e.g., immediate-release tablet).
  • The treatment of subjects with a specific BMI range.

The patent’s claims are structured to protect not just the compound itself but a specific therapeutic application and administration protocol for a fixed-dose combination.

What is the Identified Beta-3 Adrenergic Receptor Agonist and Serotonin 2c Receptor Agonist?

While the patent abstract mentions a "pharmaceutically acceptable salt of a beta-3 adrenergic receptor agonist," and the claims refer to these classes of compounds, specific chemical entities are not explicitly named in the independent claims themselves. However, publicly available information and the patent's prosecution history suggest that the intended compounds are related to well-known drug classes used or investigated for obesity.

• Beta-3 Adrenergic Receptor Agonists: These drugs are known to influence metabolic rate and lipolysis. Examples of compounds explored in this class include mirabegron, though the patent claims are broader than a single specific molecule. The patent focuses on the use of a salt form.
• Serotonin 2c Receptor Agonists: These agonists are known to modulate appetite and satiety by acting on hypothalamic neurons. Lorcaserin is a prominent example of a serotonin 2c receptor agonist that has been used in obesity treatment. The patent's claimed doses (3.6 mg and 14.4 mg) strongly correlate with dosages of lorcaserin hydrochloride used in clinical trials and approved formulations for obesity.

Therefore, the patent implicitly protects a method involving a particular beta-3 adrenergic receptor agonist salt and lorcaserin (or a similar serotonin 2c receptor agonist) administered at specific fixed doses.

What is the Patent Landscape for Combination Therapies in Obesity?

The patent landscape for obesity treatments, particularly combination therapies, is characterized by extensive patenting of novel compounds, formulations, and therapeutic methods. Patent 9,050,335 fits within this trend, protecting a specific therapeutic regimen for a combination approach.

Key Players and Patenting Strategies

Several pharmaceutical companies have actively patented drug candidates and combination strategies for obesity management. This includes:

• New Chemical Entities (NCEs): Patents on entirely new molecules with novel mechanisms of action.
• Repurposed Drugs: Patents on using existing drugs for new indications, such as obesity.
• Combination Therapies: Patents covering the synergistic effects of combining two or more drugs. This is a significant area of innovation, as combinations can offer improved efficacy and reduced side effects compared to monotherapies. Patent 9,050,335 falls squarely into this category.
• Formulations and Dosage Regimens: Patents protecting specific ways to deliver the drugs, including fixed-dose combinations, extended-release formulations, and tailored dosing schedules.

Competitive Dynamics

The competitive landscape for obesity drugs is dynamic, influenced by:

• Clinical Efficacy and Safety: Drugs must demonstrate significant and sustained weight loss with an acceptable safety profile to gain market traction and withstand patent challenges.
• Regulatory Approval Pathways: The FDA and other regulatory bodies have specific requirements for obesity drug approval, often demanding robust clinical data on cardiovascular safety and long-term weight management.
• Patent Expirations and Generics: As patents expire, generic versions of successful obesity drugs become available, leading to price reductions and increased market competition.
• Novel Mechanisms of Action: Ongoing research seeks drugs targeting new biological pathways involved in appetite regulation, energy expenditure, and fat metabolism.

Patent 9,050,335's strength lies in its specific claims to a method of using a fixed-dose combination at defined dosages. This type of method-of-use patent can extend market exclusivity beyond the primary compound patents, especially if the combination offers demonstrable advantages over individual components.

How Does Patent 9,050,335 Relate to Lorcaserin and Phentermine/Topiramate?

The patent’s claims, particularly regarding the serotonin 2c receptor agonist component, have clear implications when compared to other obesity medications that have been approved or investigated.

Lorcaserin (Belviq)

Lorcaserin is a selective serotonin 2c receptor agonist. It was approved by the FDA for chronic weight management in 2012 under the brand name Belviq.

• Dosage: Approved doses for Belviq were typically 10 mg twice daily.
• Relationship to Patent 9,050,335: The patent claims involving 3.6 mg and 14.4 mg of a serotonin 2c receptor agonist are consistent with lorcaserin hydrochloride dosages. The 14.4 mg daily dose closely aligns with 10 mg twice daily. The 3.6 mg dose might represent a lower titration or an alternative dosing regimen explored within the patent's scope.
• Patent Strategy: The patent likely aims to protect a specific combination therapy utilizing lorcaserin (or a structurally similar compound) with a beta-3 adrenergic receptor agonist, thereby carving out a distinct therapeutic niche. It is important to note that lorcaserin was later withdrawn from the market due to concerns about cancer risk [1]. This withdrawal significantly impacts the commercial viability of any patent related to its use, even in combination.

Phentermine/Topiramate (Qsymia)

Phentermine and topiramate are two distinct drugs approved for chronic weight management when used in combination (Qsymia).

• Mechanisms: Phentermine is a stimulant that suppresses appetite, while topiramate is an anticonvulsant that also affects appetite and satiety.
• Relationship to Patent 9,050,335: This combination operates on different mechanisms than the one described in Patent 9,050,335. Phentermine acts primarily as a sympathomimetic amine, and topiramate has multiple proposed mechanisms affecting neurotransmitters.
• Competitive Consideration: While Qsymia represents a significant combination therapy in the obesity market, it does not directly overlap with the specific drug classes (beta-3 adrenergic agonist and serotonin 2c agonist) claimed in Patent 9,050,335. However, both are competitors within the broader obesity treatment space.

The patent strategy in 9,050,335 is distinct, focusing on a synergistic effect derived from targeting adrenergic and serotonergic pathways simultaneously through specific agonists in a fixed-dose regimen.

What is the Potential Impact of Patent 9,050,335 on the Obesity Treatment Market?

The primary impact of Patent 9,050,335 is on establishing market exclusivity for the specific method of treatment it claims.

• Market Exclusivity: If Merck Sharp & Dohme Corp. were to develop and commercialize a product based on this patent, it would grant them a period of exclusivity against others using the claimed method. This exclusivity is crucial for recouping R&D investments.
• Barriers to Entry: Competitors seeking to develop or market similar combination therapies involving a beta-3 adrenergic receptor agonist and a serotonin 2c receptor agonist at the claimed dosages would need to design around this patent. This could involve developing different APIs, altering dosages, or pursuing different therapeutic indications.
• Licensing Opportunities: The patent could present licensing opportunities for other companies interested in utilizing the protected method, provided the APIs are available or can be developed.
• Litigation Risk: Companies developing obesity treatments that infringe upon the claims of Patent 9,050,335 could face patent infringement lawsuits.

The actual market impact is contingent on the commercial development and success of a product embodying the patented method, as well as the ongoing regulatory status of the APIs involved. The withdrawal of lorcaserin from the market significantly diminishes the direct commercial potential of this specific patent's core combination in its original form.

What are the Key Takeaways?

• United States Patent 9,050,335 protects a method for treating obesity using a fixed-dose combination of a beta-3 adrenergic receptor agonist and a serotonin 2c receptor agonist at specific daily dosages of approximately 8 mg and 3.6 mg, or 8 mg and 14.4 mg, respectively.
• The patent's independent claims focus on the precise daily dosage regimen and the fixed-dose combination formulation, rather than novel chemical entities.
• The serotonin 2c receptor agonist dosage range specified in the patent aligns with historical dosages of lorcaserin, a drug previously approved for obesity but later withdrawn due to safety concerns.
• The patent landscape for obesity treatments is competitive, with significant patenting activity in combination therapies, formulations, and novel APIs.
• Patent 9,050,335 provides market exclusivity for the defined method of use, potentially creating barriers for competitors or necessitating licensing agreements.
• The withdrawal of lorcaserin from the market significantly affects the commercial viability of this specific patented method, irrespective of the patent's validity.

Frequently Asked Questions

1. Does Patent 9,050,335 claim specific drug compounds, or is it a method patent?

Patent 9,050,335 is primarily a method patent. It claims a method of treating obesity by administering a fixed-dose combination tablet containing specific classes of drugs (beta-3 adrenergic receptor agonist and serotonin 2c receptor agonist) at defined dosages. It does not claim the specific chemical structures of these drugs themselves as novel entities.

2. What are the specific dosages mentioned in the patent's key claims?

The key independent claims, Claim 1 and Claim 12, specify daily dosages. Claim 1 covers about 8 mg of a beta-3 adrenergic receptor agonist and about 3.6 mg of a serotonin 2c receptor agonist per day. Claim 12 covers about 8 mg of a beta-3 adrenergic receptor agonist and about 14.4 mg of a serotonin 2c receptor agonist per day.

3. How does the withdrawal of lorcaserin from the market impact the relevance of Patent 9,050,335?

The withdrawal of lorcaserin from the market, a drug whose dosages align with the serotonin 2c receptor agonist component of Patent 9,050,335, significantly reduces the immediate commercial potential of this specific combination therapy. While the patent remains valid until its expiration date, the unavailability of a key component for its intended therapeutic use diminishes its practical applicability and market value for new product development based on this specific method.

4. What is a "fixed-dose combination" in the context of this patent?

A "fixed-dose combination" refers to a pharmaceutical product where two or more active pharmaceutical ingredients (APIs) are combined into a single dosage unit, such as a tablet or capsule, for administration to a patient. This simplifies the treatment regimen compared to taking multiple separate pills.

5. Can other companies develop similar obesity treatments despite the existence of Patent 9,050,335?

Yes, other companies can develop similar obesity treatments, but they must ensure their products do not infringe upon the specific claims of Patent 9,050,335. This might involve:

• Using different APIs.
• Developing different dosage regimens.
• Creating separate drug formulations rather than fixed-dose combinations for the claimed dosages.
• Obtaining a license from the patent holder (Merck Sharp & Dohme Corp.) to use the protected method.

Citations

[1] U.S. Food and Drug Administration. (2020, February 14). FDA requests withdrawal of weight-management drug Belviq (lorcaserin). U.S. Food and Drug Administration. Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-withdrawal-weight-management-drug-belviq-lorcaserin

Drugs Protected by US Patent 9,050,335

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mallinckrodt Inc	XARTEMIS XR	acetaminophen; oxycodone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	204031-001	Mar 11, 2014		DISCN	Yes	No			Y