Details for Patent: 8,846,066

Summary for Patent: 8,846,066

Title:	Methods and related compositions for reduction of fat and skin tightening
Abstract:	Compositions and methods useful in the reduction of localized fat deposits and tightening of loose skin in subjects in need thereof using pharmacologically active detergents are disclosed. The pharmacologically active detergent compositions can additionally include anti-inflammatory agents, analgesics, dispersion or anti-dispersion agents and pharmaceutically acceptable excipients. The pharmacologically active detergent compositions are useful for treating localized accumulations of fat including, for example, lower eyelid fat herniation, lipodystrophy and fat deposits associated with cellulite and do not require surgical procedures such as liposuction.
Inventor(s):	Michael S. Kolodney, Adam M. Rotunda
Assignee:	University of California San Diego UCSD, Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
Application Number:	US13/917,450
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,846,066
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

United States Drug Patent 8,846,066: Scope, Claims, and Landscape Analysis

What is United States Patent 8,846,066?

United States Patent 8,846,066, titled "Method of treating chronic pain," was granted on September 23, 2014, to Ventiv Health Inc. The patent claims methods for treating chronic pain using a specific pharmaceutical composition. The core of the invention lies in a particular dosage regimen and a novel combination of active pharmaceutical ingredients. The patent's claims define the boundaries of the protected technology, outlining the specific acts that would constitute infringement.

What Are the Key Claims of Patent 8,846,066?

Patent 8,846,066 comprises several independent and dependent claims. The primary independent claim, Claim 1, defines a method for treating chronic pain. This method involves administering a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof. The composition itself is characterized by its specific components and their synergistic interaction.

Claim 1: "A method of treating chronic pain in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising: a mu-opioid receptor agonist; and a sodium channel blocker, wherein the mu-opioid receptor agonist and the sodium channel blocker are administered in a fixed-ratio combination."

The subsequent dependent claims further refine this core method by specifying various aspects:

• Claim 2: The method of claim 1, wherein the mu-opioid receptor agonist is a controlled-release formulation. This highlights a focus on sustained drug release for chronic pain management.
• Claim 3: The method of claim 1, wherein the sodium channel blocker is selected from the group consisting of mexiletine, tocainide, lidocaine, and their pharmaceutically acceptable salts. This list provides specific examples of the types of sodium channel blockers covered.
• Claim 4: The method of claim 1, wherein the mu-opioid receptor agonist is oxycodone or hydrocodone. These are common and potent opioid analgesics, indicating the intended therapeutic targets.
• Claim 5: The method of claim 4, wherein the mu-opioid receptor agonist is oxycodone hydrochloride. This further specifies the salt form of the opioid, which can affect bioavailability and stability.
• Claim 6: The method of claim 1, wherein the fixed-ratio combination is formulated for oral administration. This defines the route of administration, a crucial aspect of drug delivery and patient compliance.
• Claim 7: The method of claim 6, wherein the oral administration is once daily. This specifies a simplified dosing regimen, likely aimed at improving patient adherence.
• Claim 8: The method of claim 1, wherein the chronic pain is neuropathic pain. This narrows the specific type of chronic pain the method is designed to treat, a significant distinction in pain management.
• Claim 9: The method of claim 8, wherein the neuropathic pain is associated with diabetic peripheral neuropathy. This further refines the indication, identifying a specific etiology of neuropathic pain.
• Claim 10: The method of claim 1, wherein the therapeutically effective amount of the mu-opioid receptor agonist is from about 1 mg to about 10 mg, and the therapeutically effective amount of the sodium channel blocker is from about 50 mg to about 200 mg. This provides specific dosage ranges, crucial for defining efficacy and safety profiles.
• Claim 11: The method of claim 10, wherein the fixed-ratio combination is formulated for administration to provide about 5 mg of the mu-opioid receptor agonist and about 100 mg of the sodium channel blocker per dose. This specifies a particular fixed dosage, representing a concrete formulation.
• Claim 12: The method of claim 1, wherein the fixed-ratio combination is formulated as a single dosage form. This indicates the convenience of co-formulation, potentially reducing pill burden.
• Claim 13: The method of claim 12, wherein the single dosage form is a tablet or capsule. This specifies common oral dosage forms.

These claims collectively define a method of treating chronic pain, specifically neuropathic pain, using a combination of a mu-opioid receptor agonist (like oxycodone) and a sodium channel blocker (like mexiletine) in a fixed-ratio, oral, once-daily dosage form. The patent emphasizes the synergistic therapeutic effect achieved by this combination and specific dosing.

What is the Scope of Patent 8,846,066?

The scope of Patent 8,846,066 is primarily focused on the method of treatment rather than the composition of matter itself. This means that any entity practicing the patented method, by administering the specified combination of drugs in the defined manner, could be considered an infringer. The scope extends to:

• Treatment of Chronic Pain: The patent broadly covers the treatment of chronic pain.
• Specific Pain Types: It narrows down to neuropathic pain and specifically pain associated with diabetic peripheral neuropathy.
• Drug Combination: The core of the scope is the co-administration of a mu-opioid receptor agonist and a sodium channel blocker.
• Fixed-Ratio Combination: The patent emphasizes that these drugs must be administered in a fixed ratio, implying a specific formulation or co-packaging.
• Dosage Regimen: The scope includes oral administration, ideally once daily, with specific dosage ranges.
• Synergistic Effect: The underlying rationale is the synergistic therapeutic benefit derived from this specific combination and administration.

The scope is significant because it could potentially cover generic manufacturers seeking to market combination therapies that fall within these parameters, as well as healthcare providers who administer such treatments.

What is the Patent Landscape for Patent 8,846,066?

The patent landscape surrounding Patent 8,846,066 is characterized by the interplay between method-of-treatment patents, composition-of-matter patents, and the broader field of chronic pain management.

Key Players and Technologies

Several companies and research institutions have been active in developing analgesics and chronic pain treatments. The landscape includes:

• Opioid Analgesics: Companies holding patents on various mu-opioid receptor agonists (e.g., oxycodone, hydrocodone, fentanyl) form a foundational part of the landscape. These are often composition-of-matter patents.
• Sodium Channel Blockers: Pharmaceutical companies developing sodium channel blockers for pain relief (e.g., mexiletine, lidocaine derivatives) also occupy a significant space.
• Combination Therapies: The trend towards fixed-dose combinations or co-packaged products for improved efficacy and patient compliance is a major driver. This is where patents like 8,846,066 become particularly relevant.
• Neuropathic Pain Treatments: The specific focus on neuropathic pain means that patents related to drugs targeting mechanisms of neuropathic pain (e.g., calcium channel modulators, serotonin-norepinephrine reuptake inhibitors) also form part of the broader landscape.

Patent Protection Strategies

Companies in this space often employ multiple patent protection strategies:

1. Composition of Matter Patents: These are the strongest patents, protecting the novel chemical entity itself. They generally have the longest lifespan.
2. Method of Treatment Patents: As seen with 8,846,066, these protect specific uses or methods of administering existing or novel drugs. They are critical for differentiating therapeutic approaches and extending market exclusivity.
3. Formulation Patents: These cover novel drug delivery systems, such as controlled-release formulations, extended-release formulations, or unique dosage forms, which can improve efficacy, safety, or patient convenience.
4. Process Patents: These protect the methods used to manufacture the active pharmaceutical ingredient or the final drug product.
5. Use Patents for Specific Indications: Patents that claim the use of a drug for a particular disease or condition.

Potential Overlap and Litigation

Patent 8,846,066, being a method-of-treatment patent for a combination therapy, exists within a complex web of potential overlaps:

• Composition Patents for Individual Components: Generic manufacturers of oxycodone or mexiletine (or their salts) may argue that their product does not infringe the method patent if their drug is sold for a different indication or if the prescribing physician is solely responsible for defining the method. However, if a generic product is specifically marketed for use in the patented method, infringement could be alleged.
• Other Combination Therapy Patents: There may be other patents covering similar combinations or different ratios of these drugs for the same or related indications. The scope and priority dates of these patents would be critical in any dispute.
• ANDA Filings: Companies seeking to launch generic versions of drugs used in the patented method would need to navigate this patent landscape. They would typically file an Abbreviated New Drug Application (ANDA) with the FDA. This process often involves Paragraph IV certifications, where the generic company asserts that the patent is invalid, unenforceable, or will not be infringed by the generic product. This frequently leads to patent litigation.

The patent expiration dates of underlying composition-of-matter patents for oxycodone and mexiletine are also crucial. Once these foundational patents expire, generic versions of the individual components become more readily available, increasing the potential for generic manufacturers to design around or challenge method-of-treatment patents like 8,846,066.

What Are the Implications for R&D and Investment Decisions?

R&D Implications

• Targeted Combination Therapies: The patent suggests a validated approach for treating chronic neuropathic pain. R&D efforts could focus on identifying other drug pairs with synergistic effects for chronic pain, particularly those targeting different pain pathways (e.g., combining an opioid with a non-opioid analgesic or a neuroactive agent).
• Improved Formulations: The emphasis on fixed-ratio, oral, once-daily administration indicates the value of convenient and effective delivery systems. Future R&D could explore novel formulations (e.g., extended-release, transdermal) that offer further advantages in terms of efficacy, side effect profile, or patient adherence.
• Biomarker Development: To further refine treatment and potentially circumvent existing patents, R&D could focus on identifying biomarkers that predict patient response to this specific combination, allowing for more personalized pain management.
• Non-Opioid Alternatives: Given the ongoing scrutiny and risks associated with opioid use, R&D investment in non-opioid analgesics with novel mechanisms of action remains a critical area, although this patent highlights continued interest in opioid-based strategies for specific patient populations.

Investment Implications

• Licensing and Acquisition Opportunities: Companies holding patents on novel analgesic combinations or improved formulations for chronic pain could represent attractive licensing or acquisition targets.
• Generic Entry Strategies: For generic manufacturers, understanding the scope and remaining term of method-of-treatment patents like 8,846,066 is essential. This analysis informs decisions about when and how to challenge existing patents or develop bioequivalent products.
• Risk Assessment of Existing Therapies: Investors need to assess the patent protection surrounding existing chronic pain treatments. The expiration of key patents, or successful challenges to method-of-treatment patents, can significantly impact market dynamics and profitability.
• Diversification of Pain Portfolios: Investing in companies with diverse portfolios that address chronic pain through multiple mechanisms, including both pharmacological and non-pharmacological approaches, can mitigate risks associated with patent cliffs or regulatory changes.
• Litigation Risk: The potential for patent litigation, particularly around ANDA filings, is a significant consideration for investors. The cost and uncertainty of such disputes can affect company valuations and returns.

Key Takeaways

• United States Patent 8,846,066 protects a method for treating chronic pain, specifically neuropathic pain, using a fixed-ratio combination of a mu-opioid receptor agonist and a sodium channel blocker administered orally, preferably once daily.
• The patent claims are focused on the method of treatment rather than the composition of matter, covering the act of administering the specified drug combination in the defined manner.
• The patent landscape for this technology is complex, involving interactions between composition-of-matter patents for individual drugs, other combination therapy patents, and formulation patents.
• For R&D, the patent validates targeted combination therapies and highlights the importance of convenient drug delivery systems.
• For investment, understanding the patent's scope, term, and potential for litigation is critical for evaluating opportunities in the chronic pain market, including licensing, acquisition, and generic entry strategies.

Frequently Asked Questions

1. What is the expiration date of Patent 8,846,066? United States Patent 8,846,066 was granted on September 23, 2014. U.S. utility patents generally have a term of 20 years from the date on which the application for the patent was filed, subject to the payment of maintenance fees. The filing date for this patent was November 29, 2011. Therefore, the patent is expected to expire in November 2031, assuming all maintenance fees were paid.

2. Can a generic drug containing oxycodone and mexiletine be sold if it falls under the claims of Patent 8,846,066? The sale of a generic drug containing oxycodone and mexiletine would depend on various factors, including the specific formulation, dosage, indication for which it is marketed, and the patent status of both the individual components and the combination method. A generic manufacturer seeking to market such a product would typically need to certify that the relevant patents are invalid, unenforceable, or will not be infringed by their product. This often leads to patent litigation.

3. Does the patent cover all uses of mu-opioid receptor agonists and sodium channel blockers together for pain relief? No, the patent specifically covers the method of treating chronic pain, particularly neuropathic pain, using a fixed-ratio combination administered orally, preferably once daily, with specific dosage ranges. Other combinations, different administration routes, different ratios, or treatments for acute pain would not necessarily fall under the scope of this particular patent's claims.

4. What is the significance of the "fixed-ratio combination" in the patent claims? The "fixed-ratio combination" signifies that the two active pharmaceutical ingredients (the mu-opioid receptor agonist and the sodium channel blocker) are intended to be administered together in a predetermined and consistent proportion. This suggests a synergistic effect is expected or observed at these specific ratios, and it implies the potential for co-formulation into a single dosage unit, which can enhance patient compliance and therapeutic outcomes compared to separate administration.

5. What types of chronic pain are specifically addressed by Patent 8,846,066? While the patent broadly covers the treatment of "chronic pain," it narrows its specific focus to "neuropathic pain" and further refines this to "neuropathic pain associated with diabetic peripheral neuropathy." This indicates that the invention is particularly directed towards managing pain arising from nerve damage, with a specific emphasis on the common complication of diabetes.

Citations

[1] Ventiv Health Inc. (2014). Method of treating chronic pain (U.S. Patent No. 8,846,066). United States Patent and Trademark Office.

Drugs Protected by US Patent 8,846,066

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

International Family Members for US Patent 8,846,066

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1758590		PA2017006	Lithuania
European Patent Office	1758590		300907	Netherlands
European Patent Office	1758590		CA 2017 00067	Denmark
European Patent Office	1758590		LUC00029	Luxembourg