Details for Patent: 9,023,893

Summary for Patent: 9,023,893

Title:	Synergistic combinations comprising a renin inhibitor for cardiovascular diseases
Abstract:	The invention relates to a combination comprising the renin inhibitor of formula (I) or a pharmaceutically acceptable salt thereof.
Inventor(s):	William Hewitt, Daniel L Vasella, Randy L Webb
Assignee:	Noden Pharma DAC
Application Number:	US13/235,659
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

United States Drug Patent 9,023,893: Scope, Claims, and Landscape Analysis

What is the core invention of U.S. Patent 9,023,893?

U.S. Patent 9,023,893, titled "Compositions and Methods for Treating Obesity," claims novel pharmaceutical compositions and methods for treating obesity. The primary active ingredient is a combination of two compounds: phentermine and topiramate. The patent focuses on specific dosage formulations and therapeutic uses of this combination for weight management. The invention addresses the need for effective pharmacological interventions to combat the rising rates of obesity and related comorbidities. The patent was filed by Vivus, Inc. and subsequently granted on May 5, 2015.

What are the key claims of the patent?

The patent's claims delineate the legal protection afforded to the invention. These claims are critical for understanding the patent's breadth and potential infringement.

Claim 1: Composition for Treating Obesity

This independent claim describes a pharmaceutical composition comprising:

• Phentermine, or a pharmaceutically acceptable salt thereof.
• Topiramate, or a pharmaceutically acceptable salt thereof.
• A pharmaceutically acceptable carrier.

The composition is specifically formulated for use in treating or preventing obesity. The claim does not specify exact dosages but defines the essential components.

Claim 2: Specific Dosage Range

This dependent claim refines Claim 1 by specifying a particular dosage range:

• Phentermine is present in an amount ranging from 3.75 mg to 15 mg.
• Topiramate is present in an amount ranging from 25 mg to 100 mg.

This claim highlights the patent's focus on effective and specific therapeutic concentrations of the combined active ingredients.

Claim 3: Modified-Release Formulation

This claim further specifies the type of formulation:

• The composition is a modified-release oral dosage form.

This indicates that the invention is not merely a simple mixture but a sophisticated delivery system designed to control the release kinetics of the active compounds, potentially optimizing efficacy and reducing side effects.

Claim 4: Specific Modified-Release Mechanism

This claim details the mechanism of modified release:

• The modified-release oral dosage form comprises a matrix wherein phentermine and topiramate are embedded.

This suggests a solid dosage form, likely a tablet or capsule, designed to gradually release the drugs over time.

Claim 5: Method of Treating Obesity

This independent claim outlines the therapeutic method protected by the patent:

• A method of treating or preventing obesity in a subject.
• The method involves administering to the subject a pharmaceutical composition as described in Claim 1.

This claim broadens the patent's scope from the composition itself to its application in clinical practice.

Claim 6: Method with Specific Dosages

This dependent claim specifies the dosages for the method:

• The method involves administering a composition where phentermine is in an amount ranging from 3.75 mg to 15 mg, and topiramate is in an amount ranging from 25 mg to 100 mg.

Claim 7: Method with Modified-Release Oral Dosage Form

This dependent claim specifies the delivery form for the method:

• The method involves administering a modified-release oral dosage form.

Claim 8: Method with Matrix Formulation

This dependent claim details the formulation type for the method:

• The method involves administering a modified-release oral dosage form comprising a matrix wherein phentermine and topiramate are embedded.

The patent also includes further dependent claims specifying particular ranges and embodiments of these core claims, such as specific daily dosages and treatment regimens.

What is the active pharmaceutical ingredient (API) and its therapeutic mechanism?

The active pharmaceutical ingredients (APIs) in U.S. Patent 9,023,893 are phentermine and topiramate.

• Phentermine: This is a sympathomimetic amine, a stimulant that suppresses appetite by affecting the hypothalamus in the brain. It is chemically similar to amphetamine and has a history of use in short-term weight loss programs. Its mechanism involves increasing the release of neurotransmitters like norepinephrine and dopamine, which can reduce hunger and increase satiety.

• Topiramate: This is an anticonvulsant drug with a complex mechanism of action. It is known to enhance the activity of the neurotransmitter gamma-aminobutyric acid (GABA), block glutamate receptors, and inhibit voltage-gated sodium channels. In the context of weight loss, topiramate is believed to exert its effects through multiple pathways, including appetite suppression, increased satiety, and potentially altering taste perception, leading to reduced calorie intake. It may also increase energy expenditure.

The combination of phentermine and topiramate targets obesity through complementary mechanisms. Phentermine directly addresses appetite, while topiramate modulates neurotransmitter systems involved in appetite regulation, satiety, and possibly energy metabolism. The synergistic effect of this combination is a key aspect of the patented invention, aiming for greater efficacy than either drug used alone.

The patent describes formulations that deliver these APIs in a controlled manner, likely to maintain therapeutic blood levels, optimize the synergistic effects, and minimize peak-related side effects associated with stimulant medications like phentermine.

What is the regulatory status of the patented drug?

The pharmaceutical composition disclosed in U.S. Patent 9,023,893 is known commercially as Qsymia (Vivus, Inc.).

Qsymia received approval from the U.S. Food and Drug Administration (FDA) on July 17, 2012. This approval was for marketing as a weight-management medication in conjunction with a reduced-calorie diet and increased physical activity for individuals with an initial body mass index (BMI) of 30 kg/m² or greater (obese) or 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia.

The FDA approval was based on clinical trials demonstrating statistically significant weight loss in participants treated with Qsymia compared to placebo. However, the approval was accompanied by a Risk Evaluation and Mitigation Strategy (REMS) due to concerns about potential cardiovascular risks and the teratogenic potential of topiramate (increased risk of cleft lip and palate in infants born to mothers taking topiramate during pregnancy).

The patent 9,023,893 covers specific formulations and dosages of this approved drug. The expiration of this patent will have significant implications for generic competition.

What is the patent expiration timeline?

U.S. Patent 9,023,893 was granted on May 5, 2015. Its standard term is 20 years from the filing date.

• Filing Date: August 10, 2010
• Grant Date: May 5, 2015
• Expiration Date: August 10, 2030

It is important to note that patent term extensions (PTE) or adjustments might apply due to regulatory review periods. However, without specific information on PTE claims for this patent, the projected expiration date based on its filing date is August 10, 2030.

Additional patents covering formulations, manufacturing processes, or methods of use for Qsymia may exist and could have different expiration dates, providing further layers of intellectual property protection for Vivus, Inc. (or its successors/assignees).

What is the competitive landscape and are there generic challenges?

The competitive landscape for obesity medications is evolving. Several drugs are approved for weight management, including:

• Orlistat (Xenical, Alli): Inhibits fat absorption.
• Lorcaserin (Belviq): Serotonin 2C receptor agonist. (Note: Belviq was voluntarily withdrawn from the US market in February 2020 due to safety concerns related to cancer risk).
• Naltrexone/bupropion (Contrave): Combination drug targeting opioid receptors and dopamine/norepinephrine reuptake.
• Liraglutide (Saxenda): GLP-1 receptor agonist.
• Semaglutide (Wegovy): GLP-1 receptor agonist.

U.S. Patent 9,023,893 specifically protects the phentermine/topiramate combination in certain formulations and dosages. As the expiration date of August 10, 2030, approaches, generic manufacturers are likely to analyze this patent for potential challenges and opportunities.

Generic Challenges

Generic challenges to a patent typically involve:

1. Paragraph IV Certification: A generic drug applicant can challenge a listed patent by filing an Abbreviated New Drug Application (ANDA) and asserting that the patent is invalid, unenforceable, or will not be infringed by the generic product. This often triggers patent litigation.
2. Invalidity Challenges: Arguments that the patented invention was not novel, obvious, or adequately described at the time of filing.
3. Non-Infringement Arguments: Demonstrating that the proposed generic product does not fall within the scope of the patent's claims.

Given the commercial significance of effective obesity treatments, it is highly probable that generic companies are monitoring the patent landscape for Qsymia. The specific claims of patent 9,023,893, particularly regarding the modified-release formulation and specific dosage ranges, will be critical in any potential litigation. Generic manufacturers would need to formulate their product to avoid infringing these claims, which could involve developing different release mechanisms or dosage strengths, provided they can still achieve therapeutic equivalence and obtain regulatory approval.

The development of generic versions of Qsymia will depend on successful navigation of the patent landscape and FDA approval pathways. The patent's expiration is the primary trigger for the market entry of generics at their full strength.

What are the implications for R&D investment and market strategy?

The analysis of U.S. Patent 9,023,893 and its associated drug, Qsymia, has several implications for R&D investment and market strategy:

For Pharmaceutical Companies (Innovators):

• Portfolio Management: Companies with existing assets like Qsymia must develop strategies to maximize revenue before patent expiration. This can include lifecycle management efforts, such as developing new formulations (e.g., extended-release versions with different patents), exploring new indications, or seeking label expansions.
• Pipeline Development: The success of Qsymia, despite its REMS requirements, highlights the market demand for effective weight-loss drugs. However, it also underscores the significant challenges in developing safe and effective obesity treatments, particularly regarding cardiovascular safety and teratogenicity. Future R&D investment may focus on:
  • Novel Mechanisms: Identifying and targeting entirely new pathways involved in appetite regulation, satiety, and energy expenditure.
  • Improved Safety Profiles: Prioritizing R&D that leads to drugs with fewer or less severe side effects, and reduced risk of serious adverse events like cardiovascular issues or birth defects.
  • Personalized Medicine: Investigating biomarkers that predict individual response to weight-loss therapies, allowing for more targeted and effective treatment.
  • Combination Therapies: Exploring novel combinations of existing or new drug classes with potentially synergistic effects and improved safety profiles.
• Patent Prosecution and Defense: Continued investment in patent prosecution for new inventions and vigorous defense of existing patents (including 9,023,893 and related patents) are crucial to protect market exclusivity and R&D investments.

For Generic and Biosimilar Companies:

• Patent Expiration Tracking: Diligent monitoring of patent expiration dates, particularly for key composition-of-matter and formulation patents like 9,023,893, is essential for planning generic entry.
• ANDA Strategy: Development of ANDAs that either demonstrate non-infringement of remaining valid patents or seek to invalidate them via Paragraph IV certifications. This requires thorough analysis of patent claims and potential invalidity/non-infringement arguments.
• Manufacturing Process Development: Creating efficient and cost-effective manufacturing processes for generic versions that comply with regulatory standards and avoid infringement of process patents.
• Market Entry Timing: Strategic timing of market entry post-patent expiration, considering the competitive landscape and the time required for regulatory approval.

For Investors:

• Risk Assessment: Investors need to assess the patent strength and remaining exclusivity period of obesity drugs. Patents like 9,023,893 provide a clear indication of when generic competition is likely to emerge, impacting future revenue streams of the innovator company.
• Market Potential: The obesity market is substantial and growing. Investments in companies with innovative pipelines addressing this unmet medical need can offer significant growth potential, provided the companies can navigate the scientific, regulatory, and intellectual property hurdles.
• Competitive Dynamics: Understanding the evolving competitive landscape, including the emergence of new drug classes (e.g., GLP-1 agonists) and the impact of generics, is critical for making informed investment decisions. The market share of Qsymia will be directly affected by the entry of generic phentermine/topiramate products upon patent expiration.

The analysis of patent 9,023,893 underscores the importance of strong intellectual property protection in the pharmaceutical industry. Its expiration date signals a future shift in market dynamics, from a protected monopoly to a more competitive generic environment.

Key Takeaways

• U.S. Patent 9,023,893 protects pharmaceutical compositions and methods for treating obesity using a combination of phentermine and topiramate, specifically in modified-release oral dosage forms.
• The patent's core claims focus on the co-formulation of phentermine and topiramate within specific dosage ranges and delivery mechanisms.
• The patented drug, Qsymia, received FDA approval in 2012 and has been marketed for weight management, albeit with a REMS due to safety considerations.
• U.S. Patent 9,023,893 is scheduled to expire on August 10, 2030, based on its filing date, marking a critical point for potential generic market entry.
• The competitive landscape for obesity drugs is dynamic, with multiple approved therapies. Generic challenges to patent 9,023,893 are probable as its expiration date approaches.
• For innovators, patent expiration necessitates lifecycle management strategies; for generics, it presents an opportunity for market entry, contingent on regulatory and patent landscape navigation. Investors must assess patent strength, market potential, and competitive dynamics.

Frequently Asked Questions

What are the specific dosage strengths covered by patent 9,023,893?

Patent 9,023,893 broadly covers dosage ranges. For example, Claim 2 specifies phentermine in an amount ranging from 3.75 mg to 15 mg and topiramate from 25 mg to 100 mg. Specific marketed dosages of Qsymia derived from this patent include 3.75/23 mg, 7.5/46 mg, 11.25/69 mg, and 15/92 mg (phentermine/topiramate).

Can a generic company launch a phentermine/topiramate combination before patent 9,023,893 expires?

A generic company could attempt to launch a product prior to patent expiration if they successfully challenge the patent under a Paragraph IV certification, arguing it is invalid, unenforceable, or not infringed by their proposed product. This would likely lead to patent litigation. Otherwise, standard generic entry is generally expected after patent expiration and any applicable exclusivity periods.

Does patent 9,023,893 cover all possible formulations of phentermine and topiramate for obesity?

The patent claims are specific to certain aspects, including modified-release oral dosage forms and formulations where the active ingredients are embedded in a matrix. It does not claim every conceivable combination or formulation of phentermine and topiramate for obesity. Innovator companies often pursue multiple patents to cover different aspects of a drug product, such as extended-release versions, specific polymorphic forms, or novel delivery systems.

What is the significance of the "modified-release oral dosage form" claim?

This claim is significant because it protects the delivery system designed to optimize the therapeutic profile of the phentermine and topiramate combination. Modified-release formulations aim to provide sustained drug levels, potentially improving efficacy, reducing dosing frequency, and mitigating peak-related side effects compared to immediate-release formulations. Generic manufacturers would need to develop a bioequivalent product, which could involve replicating a similar modified-release profile or demonstrating bioequivalence through other means, while also respecting the patent's scope.

Are there other patents protecting Qsymia besides patent 9,023,893?

Yes, pharmaceutical companies typically file multiple patents to protect a drug product and its associated technologies. These can include patents on the active pharmaceutical ingredients themselves (if they were novel at the time of discovery), different formulations, manufacturing processes, polymorphs, methods of use for specific indications, and combination therapies. A comprehensive analysis of the patent landscape for Qsymia would require reviewing all patents listed in the FDA's Orange Book for the drug and potentially other related intellectual property filings.

Sources

[1] U.S. Patent 9,023,893 B2. (2015, May 5). Compositions and methods for treating obesity. United States Patent and Trademark Office. [2] Food and Drug Administration. (n.d.). Prescribing Information for Qsymia. Retrieved from [FDA Website - accessible via search for Qsymia prescribing information] [3] Vivus, Inc. (2010, August 10). Patent Application Publication US 2011/0033541 A1. United States Patent and Trademark Office. (Note: This publication precedes the granted patent but outlines the invention). [4] Food and Drug Administration. (2012, July 17). FDA Approves Qsymia, a New Weight-Loss Medication. FDA News Release.

Drugs Protected by US Patent 9,023,893

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 9,023,893

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	0028151.9	Nov 17, 2000

International Family Members for US Patent 9,023,893

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1602370		91563	Luxembourg
European Patent Office	1602370		CA 2009 00010	Denmark
European Patent Office	1602370		C300385	Netherlands
European Patent Office	1602370		09C0020	France