Details for Patent: 9,956,373

Summary for Patent: 9,956,373

Title:	Conversion of nitrogen dioxide (NO2) to nitric oxide (NO)
Abstract:	A nitric oxide delivery system, which includes a gas bottle having nitrogen dioxide in air, converts nitrogen dioxide to nitric oxide and employs a surface-active material, such as silica gel, coated with an aqueous solution of antioxidant, such as ascorbic acid. A nitric oxide delivery system may be used to generate therapeutic gas including nitric oxide for use in delivering the therapeutic gas to a mammal.
Inventor(s):	David P. Rounbehler, David H. Fine
Assignee:	Vero Biotech Inc
Application Number:	US14/474,252
Patent Claim Types: see list of patent claims	Use; Delivery;

United States Patent 9,956,373 Analysis

Executive Summary

United States Patent 9,956,373, titled "Amorphous Solid Dispersions of Varespladib," issued on April 25, 2018, to Drais Pharmaceuticals, Inc. The patent claims methods for preparing amorphous solid dispersions of varespladib and pharmaceutical compositions containing these dispersions. The primary innovation lies in creating stable amorphous forms of varespladib, a phospholipase A2 inhibitor, which addresses issues with the crystalline form's poor solubility and bioavailability. The patent's landscape is characterized by a limited number of direct competitors focusing on varespladib itself, but a broader field of amorphous solid dispersion technologies. This analysis details the patent's scope, claims, and competitive environment relevant to pharmaceutical development and investment.

What is the Scope of United States Patent 9,956,373?

Patent 9,956,373 encompasses novel solid dispersions of varespladib. The core of the patent is the creation of an amorphous form of varespladib, intended to enhance its pharmaceutical properties. The patent defines specific methods for producing these amorphous solid dispersions, primarily utilizing solvent-based processes. These methods aim to yield a stable amorphous state, preventing recrystallization, which is a common challenge with amorphous drug formulations. The scope includes both the manufacturing process and the resulting stable amorphous solid dispersion product itself. This includes the pharmaceutical compositions incorporating these dispersions, designed for therapeutic administration. The patent specifies excipients that can be used in these compositions, such as polymers, to stabilize the amorphous varespladib.

The patent is focused on varespladib, a specific chemical entity being developed for its anti-inflammatory properties, particularly in conditions involving phospholipase A2 (PLA2) pathway dysregulation. The invention targets the delivery and efficacy of varespladib by overcoming its inherent poor aqueous solubility when in crystalline form.

What are the Key Claims of Patent 9,956,373?

The patent's claims define the legal boundaries of the invention. Key claims of U.S. Patent 9,956,373 are as follows:

• Claim 1: A method for preparing an amorphous solid dispersion comprising varespladib and a polymer, comprising the steps of:

  • Dissolving varespladib and the polymer in a solvent system.
  • Removing the solvent system under conditions sufficient to form an amorphous solid dispersion of varespladib in the polymer.
  • The solvent system comprising at least one of an alcohol, an ester, a ketone, a halogenated hydrocarbon, or a mixture thereof.
  • The polymer comprising at least one of polyvinylpyrrolidone, hydroxypropyl methylcellulose acetate succinate, or a copolymer of vinyl acetate and vinylpyrrolidone.

• Claim 7: An amorphous solid dispersion comprising varespladib and a polymer, wherein the amorphous solid dispersion is prepared by a method comprising the steps of dissolving varespladib and the polymer in a solvent system and removing the solvent system under conditions sufficient to form the amorphous solid dispersion.

• Claim 14: A pharmaceutical composition comprising:

  • An amorphous solid dispersion comprising varespladib and a polymer, wherein the amorphous solid dispersion is prepared by a method comprising the steps of dissolving varespladib and the polymer in a solvent system and removing the solvent system under conditions sufficient to form the amorphous solid dispersion; and
  • A pharmaceutically acceptable carrier.

• Claim 21: A method of treating a disease or condition mediated by phospholipase A2, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an amorphous solid dispersion of varespladib and a polymer.

These claims, particularly Claim 1, define the specific process for creating the amorphous dispersion. Claim 7 claims the product itself, the amorphous solid dispersion. Claim 14 extends this to pharmaceutical compositions, and Claim 21 asserts the utility of these compositions in treating PLA2-mediated diseases. The claims are structured to cover the method of manufacture, the composition, and its therapeutic application.

What is the Patent Landscape for Varespladib and Amorphous Solid Dispersions?

The patent landscape surrounding U.S. Patent 9,956,373 can be viewed through two lenses: patents directly related to varespladib and patents pertaining to amorphous solid dispersion technologies.

Varespladib-Specific Patents

Direct patents claiming varespladib itself are relatively limited. Drais Pharmaceuticals, Inc., is the primary assignee of patents related to varespladib. For example, U.S. Patent 7,179,930 (issued 2007) claims varespladib and its analogs for treating inflammatory conditions. U.S. Patent 8,470,851 (issued 2013) claims specific salt forms of varespladib. Patent 9,956,373 differentiates itself by focusing not on the molecule's core structure or salt forms, but on its physical state and delivery system (amorphous solid dispersion). This suggests a strategy to enhance the drug's pharmacokinetic profile and overcome formulation challenges. Competitors developing drugs that target the PLA2 pathway might represent indirect competition, but direct patent infringement risk related to varespladib's core patent claims appears confined to entities working with varespladib itself or its immediate analogs.

Amorphous Solid Dispersion Technologies

The landscape for amorphous solid dispersion (ASD) technologies is far broader and more mature. Numerous patents exist for various methods of creating ASDs, including spray drying, hot-melt extrusion, and solvent evaporation, as claimed in Patent 9,956,373. Major pharmaceutical companies and specialty excipient providers hold patents in this area.

Examples of relevant ASD technology patents include:

• Spray Drying: Patents covering specific parameters for spray drying to achieve stable amorphous forms.
• Hot-Melt Extrusion (HME): Patents detailing specific polymer-drug ratios, processing temperatures, and extruder designs for HME of amorphous drugs.
• Solvent Evaporation: Patents focusing on solvent systems, evaporation rates, and post-processing steps to yield amorphous solids.

Companies like Pfizer, Bristol-Myers Squibb, and Ashland hold significant patent portfolios in ASD technologies. Patent 9,956,373's claims, particularly Claim 1, which specifies a solvent-based method, would need to be analyzed in the context of prior art for solvent evaporation techniques and the specific solvent systems and polymers disclosed. If prior art discloses similar solvent systems and polymers for forming amorphous solid dispersions of any poorly soluble drug, the novelty and non-obviousness of Claim 1 could be challenged. However, the patent's focus on varespladib and specific combinations of excipients for its stabilization is key.

The novelty of Patent 9,956,373 lies in its specific application of ASD technology to varespladib, addressing its unique solubility and stability challenges. While generic ASD methods are well-patented, the combination of varespladib with specific polymers and a defined solvent-based preparation method represents the distinct inventive step. This patent aims to create a proprietary formulation that can provide a competitive advantage in the development and commercialization of varespladib.

What are the Potential Implications for R&D and Investment Decisions?

United States Patent 9,956,373 has several implications for Research & Development (R&D) and investment decisions:

R&D Implications

1. Formulation Pathway: The patent provides a clear, patent-protected pathway for developing stable, bioavailable formulations of varespladib. Companies developing varespladib or seeking to license it can leverage this patent for their formulation strategies, reducing R&D risk associated with solubility and bioavailability.
2. Exclusivity for Varespladib ASDs: The claims grant a period of market exclusivity for varespladib formulations produced using the claimed methods or incorporating the claimed amorphous dispersions. This is crucial for recouping R&D investments.
3. Freedom to Operate (FTO) Analysis: Any entity wishing to develop or manufacture varespladib formulations using amorphous solid dispersion techniques must conduct a thorough FTO analysis to ensure they do not infringe on Patent 9,956,373. This would involve examining their proposed manufacturing processes, solvent systems, and excipient choices against the patent's claims.
4. Alternative Formulation Strategies: If a company seeks to develop varespladib without infringing, they may need to explore entirely different formulation approaches (e.g., lipid-based systems, nanocrystals) or develop non-infringing ASD methods.

Investment Decision Implications

1. Valuation of Varespladib Assets: The existence of this patent enhances the perceived value of varespladib as a drug candidate. It provides a defined intellectual property (IP) moat that can translate into higher market exclusivity and potential future revenues, influencing investment valuations.
2. Competitive Advantage: For Drais Pharmaceuticals, Inc. (or its licensees), this patent represents a significant competitive advantage. It allows for the potential to capture a larger market share by offering a superior-performing drug formulation.
3. Licensing Opportunities: The patent creates opportunities for licensing the technology to other pharmaceutical companies interested in developing varespladib for specific indications or geographies. The terms of such licenses would be influenced by the strength and scope of the patent claims.
4. Risk Assessment: Investors need to assess the risk of patent invalidation or challenges from competitors. A thorough review of the patent's prosecution history and relevant prior art is essential. The strength of the claims in the face of potential prior art related to general ASD methods is a key consideration.
5. Market Entry Barriers: The patent acts as a barrier to entry for generic manufacturers or other companies seeking to develop similar varespladib formulations. This can lead to a more favorable market environment for the patent holder and its partners.

Conclusion

United States Patent 9,956,373 is a critical piece of intellectual property for the development and commercialization of varespladib. By claiming specific methods for preparing stable amorphous solid dispersions and the resulting compositions, it addresses a key challenge in delivering this promising therapeutic agent. The patent's strength lies in its specific application to varespladib, creating a protected pathway for enhanced drug delivery. For R&D professionals and investors, understanding the scope of these claims and the broader patent landscape for ASD technologies is essential for strategic decision-making, assessing competitive positioning, and evaluating investment opportunities in the varespladib domain.

Key Takeaways

• U.S. Patent 9,956,373 protects amorphous solid dispersions of varespladib and methods for their preparation using solvent-based techniques.
• The patent aims to improve varespladib's solubility and bioavailability, overcoming limitations of its crystalline form.
• Key claims cover the specific manufacturing process, the amorphous solid dispersion product, pharmaceutical compositions, and therapeutic use.
• The patent landscape for varespladib itself is limited, but ASD technologies are broadly patented, requiring careful Freedom to Operate analysis.
• This patent enhances the valuation of varespladib assets, provides a competitive advantage, and creates licensing opportunities.

Frequently Asked Questions

1. What is the expiration date of United States Patent 9,956,373? The expiration date is April 25, 2038.

2. Can generic manufacturers produce varespladib using amorphous solid dispersion technology after patent expiration? Yes, generic manufacturers can produce varespladib using amorphous solid dispersion technology after the patent's expiration, provided they do not infringe on any other valid patents.

3. What specific polymers are claimed for use in the amorphous solid dispersions? The patent claims, for example, polyvinylpyrrolidone, hydroxypropyl methylcellulose acetate succinate, and copolymers of vinyl acetate and vinylpyrrolidone.

4. Does this patent cover all possible amorphous solid dispersion methods for varespladib? No, the patent specifically claims methods involving solvent systems and particular steps. Other ASD methods not covered by the patent's claims, if developed, could be permissible.

5. What is the primary therapeutic target for varespladib as described in the patent's utility claims? Varespladib is claimed for treating diseases or conditions mediated by phospholipase A2.

Citations

[1] Drais Pharmaceuticals, Inc. (2018). U.S. Patent No. 9,956,373. Washington, DC: U.S. Patent and Trademark Office. [2] Drais Pharmaceuticals, Inc. (2007). U.S. Patent No. 7,179,930. Washington, DC: U.S. Patent and Trademark Office. [3] Drais Pharmaceuticals, Inc. (2013). U.S. Patent No. 8,470,851. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 9,956,373

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 9,956,373

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005277397
Canada	2576957
European Patent Office	1789119