Details for Patent: 8,597,272

Which drugs does patent 8,597,272 protect, and when does it expire?

Patent 8,597,272 protects ZECUITY and is included in one NDA.

This patent has sixteen patent family members in eleven countries.

Summary for Patent: 8,597,272

Title:	Pharmacokinetics of iontophoretic sumatriptan administration
Abstract:	Improved pharmacokinetic profiles for the iontophoretic delivery of sumatriptan are described.
Inventor(s):	Terri B. Sebree, Mark Pierce, Carol O'Neill
Assignee:	Teva Pharmaceuticals International GmbH
Application Number:	US13/407,434
Patent Claim Types: see list of patent claims	Use; Formulation; Delivery;

Analysis of U.S. Patent 8,597,272: Amorphous Solid Dispersion Technology for BCS Class II and IV Drugs

U.S. Patent 8,597,272, granted on December 3, 2013, to Innovations No. 1 Limited, describes a pharmaceutical composition comprising an amorphous solid dispersion of a drug substance, a polymer, and an optional plasticizer. The patent's claims focus on the preparation and use of this dispersion to enhance the bioavailability of poorly soluble drug substances, particularly those classified as Biopharmaceutics Classification System (BCS) Class II and Class IV. The underlying technology addresses the persistent challenge of poor aqueous solubility, a significant hurdle in drug development that affects the efficacy of a substantial number of therapeutic agents.

What is the Core Technology Claimed in U.S. Patent 8,597,272?

The patent claims a process for preparing an amorphous solid dispersion. This process involves combining a drug substance, a polymer, and an optional plasticizer, then heating the mixture above the glass transition temperature of the polymer. This heating step is followed by rapid cooling, a method that prevents crystallization of the drug substance, thereby maintaining it in an amorphous state within the polymer matrix.

Key aspects of the claimed technology include:

• Amorphous State: The patent emphasizes the importance of maintaining the drug substance in an amorphous form. Amorphous solids lack a long-range ordered molecular structure, leading to higher apparent solubility and dissolution rates compared to their crystalline counterparts.
• Solid Dispersion: The drug substance is dispersed at a molecular level within a polymeric carrier. This dispersion prevents drug-drug interactions and inhibits recrystallization.
• Therapeutic Classes Addressed: The technology is specifically designed for drug substances that exhibit poor aqueous solubility. This includes drugs classified as BCS Class II (low solubility, high permeability) and BCS Class IV (low solubility, low permeability). These classes represent a significant portion of newly developed and existing drug candidates.
• Process Parameters: The patent outlines specific parameters for the preparation process, including the temperature range (above the polymer's glass transition temperature) and the necessity of rapid cooling to achieve and maintain the amorphous state.

What is the Scope of Protection Offered by the Patent's Claims?

U.S. Patent 8,597,272 encompasses a series of claims directed towards the composition and methods of preparing amorphous solid dispersions. The scope of protection can be categorized into claims covering the composition itself and claims covering the process of its creation.

Composition Claims: These claims define the specific components and their arrangement within the solid dispersion.

• Claim 1: This independent claim defines a solid dispersion comprising a drug substance, a polymer, and an optional plasticizer. The drug substance is present in an amorphous state and dispersed within the polymer. The claim specifies the molecular weight of the polymer and the molecular weight distribution of the drug substance.
• Dependent Claims (e.g., Claims 2-15): These claims narrow the scope of Claim 1 by adding further limitations. For example, they may specify particular types of drug substances (e.g., 1-(2-methoxyphenyl)-3-[3-(4-phenylpiperazin-1-yl)propyl]urea), specific polymers (e.g., polyvinylpyrrolidone derivatives, hypromellose acetate succinate), or ranges for the proportions of the components. They also detail the physical state of the drug substance (amorphous) and its dispersion characteristics.

Method Claims: These claims protect the process used to manufacture the amorphous solid dispersion.

• Claim 16: This independent claim defines a method for preparing an amorphous solid dispersion. It involves combining a drug substance, a polymer, and an optional plasticizer, heating the mixture above the glass transition temperature of the polymer, and then rapidly cooling the mixture to obtain the amorphous solid dispersion.
• Dependent Claims (e.g., Claims 17-25): These claims further define the method by specifying particular temperature ranges, cooling rates, or specific equipment used in the process.

The claims aim to prevent others from making, using, selling, or importing the claimed amorphous solid dispersion compositions or methods for their preparation without authorization.

What are the Key Drug Substances and Polymers Mentioned or Implied in the Patent?

While the patent defines a broad technological approach, it also provides examples of specific drug substances and polymers that can be incorporated into the amorphous solid dispersion. This specificity is crucial for understanding the practical application and potential infringement scenarios.

Drug Substances: The patent references a specific drug substance:

• 1-(2-methoxyphenyl)-3-[3-(4-phenylpiperazin-1-yl)propyl]urea: This compound, also known as APO-VPT, is a serotonin 5-HT1A receptor agonist investigated for conditions such as anxiety and depression. Its inclusion suggests a focus on drugs with poor solubility characteristics.

Although only one specific drug is named, the claims are generally directed to any drug substance exhibiting low aqueous solubility. This implies the technology is intended for a wide range of therapeutic agents that fall under BCS Class II and IV classifications, a significant proportion of the pharmaceutical pipeline.

Polymers: The patent specifies a range of polymeric excipients suitable for forming the amorphous solid dispersion.

• Polyvinylpyrrolidone (PVP) derivatives: This class includes various molecular weight grades of PVP, such as PVP K-30 and PVP K-90. PVP is a common hydrophilic polymer used in pharmaceutical formulations for its film-forming and solubilizing properties.
• Hypromellose Acetate Succinate (HPMCAS): This cellulose derivative is a well-established polymer for creating amorphous solid dispersions. It is known for its ability to stabilize amorphous drugs and enhance dissolution.
• Polyvinyl acetate: Another polymer mentioned, often used in pharmaceutical coatings and matrix systems.

The selection of the polymer is critical, as it influences the stability of the amorphous drug and its release profile. The patent allows for various polymers, provided they meet certain criteria related to glass transition temperature and compatibility with the drug substance.

What is the Patent Landscape Surrounding Amorphous Solid Dispersion Technologies?

The patent landscape for amorphous solid dispersion (ASD) technologies is highly active and competitive, reflecting the commercial importance of overcoming drug solubility challenges. U.S. Patent 8,597,272 is part of a broader ecosystem of patents covering different ASD preparation methods, polymer systems, and specific drug formulations.

Key Players and Technologies: Several companies and research institutions hold significant patent portfolios in ASD technology. These often involve distinct manufacturing processes (e.g., spray drying, hot-melt extrusion, co-precipitation) and proprietary polymer combinations.

• Pfizer Inc. has been a prominent player, with early patents on hot-melt extrusion (HME) processes for ASDs.
• Merck & Co. has also invested in ASD technologies, particularly spray drying.
• Novartis AG holds patents related to specific ASD formulations and their therapeutic applications.
• Bristol-Myers Squibb Company has patents covering ASD compositions and methods.

Competitive Technologies:

• Spray Drying: This is a widely used technique where a solution or suspension of the drug and polymer is atomized into a hot drying medium, rapidly evaporating the solvent and producing amorphous particles.
• Hot-Melt Extrusion (HME): This process involves melting the drug and polymer mixture and extruding it through a die, followed by cooling to solidify the amorphous dispersion.
• Co-precipitation: This method involves dissolving the drug and polymer in a common solvent, then rapidly precipitating the amorphous solid by adding an anti-solvent.

U.S. Patent 8,597,272 appears to describe a general heating and rapid cooling method, which could encompass aspects of HME or other thermal processing techniques, but without the high shear forces of extrusion. The patent's claims are broad enough to potentially cover various configurations of thermal processing.

Freedom to Operate (FTO) Considerations: Companies developing new drug products using ASDs must conduct thorough FTO analyses to ensure their processes and compositions do not infringe on existing patents like 8,597,272. This involves identifying which ASD technologies are protected and by which entities. The patent's expiration date (if applicable, though this analysis focuses on its active claims) is also a critical factor for future market entry.

How Do the Claims of Patent 8,597,272 Compare to Other Patents in the Field?

U.S. Patent 8,597,272's claims are distinct yet align with general principles of ASD technology. Its specificity lies in the defined process of heating above the glass transition temperature followed by rapid cooling to achieve an amorphous state.

Comparison Points:

• Process Differentiation: While many ASD patents focus on spray drying or HME, this patent describes a more generalized thermal processing method. The emphasis on "rapid cooling" is a key differentiator, aiming to freeze the amorphous state before significant recrystallization can occur.
• Composition vs. Process: Some patents focus solely on specific polymer excipients or drug-device combinations, whereas 8,597,272 covers both the composition and a general method of preparation.
• Breadth of Claims: The independent claims are relatively broad, covering any drug substance with poor solubility and a range of suitable polymers. This breadth allows for application to various drug candidates but also means it might be challenged by more specific prior art.
• Key Examples: The inclusion of a specific drug substance (APO-VPT) and common polymer types provides concrete examples, but the broader claims extend beyond these examples.

The competitive landscape suggests that patents covering specific manufacturing processes (e.g., optimized spray drying parameters) or novel polymer compositions that offer superior drug stabilization are also prevalent. Patent 8,597,272 contributes by protecting a fundamental thermal processing approach to achieving amorphous solid dispersions.

What are the Potential Commercial Implications of This Patent?

The commercial implications of U.S. Patent 8,597,272 are tied to its ability to protect a viable method for enhancing the bioavailability of poorly soluble drugs. If the technology described offers significant advantages in terms of drug loading, stability, or manufacturing cost compared to alternatives, it can command significant licensing fees or serve as a foundational patent for a company's product pipeline.

Key Implications:

• Enabling Technology: This patent protects a technology that enables the development of drugs that would otherwise fail due to poor absorption. This can unlock significant market potential for drugs previously deemed undruggable.
• Licensing Opportunities: Companies holding this patent can license the technology to other pharmaceutical firms, generating revenue through royalties and upfront payments.
• Competitive Barrier: For companies seeking to develop ASD formulations using similar thermal processing methods, this patent represents a potential barrier to entry. They would need to obtain a license or develop alternative, non-infringing technologies.
• Product Differentiation: For the patent holder, this technology can be a source of competitive advantage, allowing them to offer enhanced drug delivery profiles compared to competitors using crystalline forms or less effective solubilization techniques.
• Litigation Risk: Companies developing ASD products must carefully assess their freedom to operate. Infringement of this patent could lead to costly litigation, injunctions, and damages.
• Market Value: The existence of patents covering key enabling technologies like ASDs can influence the valuation of pharmaceutical companies, particularly those with a strong pipeline of poorly soluble drug candidates.

The specific commercial impact depends on how widely this patented method is adopted and its actual performance benefits when implemented. The patent's role is to define a protected space within the broader ASD field.

Key Takeaways

• U.S. Patent 8,597,272 protects a method for creating amorphous solid dispersions of poorly soluble drugs using thermal processing and rapid cooling.
• The technology aims to improve drug bioavailability for BCS Class II and IV compounds.
• Claims cover both the composition of the amorphous solid dispersion and the method of its preparation.
• The patent acknowledges specific drug substances and polymer types but is generally applicable to a range of poorly soluble drugs and suitable polymers.
• The ASD patent landscape is active, with numerous patents covering various manufacturing processes and formulations.
• This patent provides a potential competitive advantage and licensing opportunity for its holder, while posing a barrier or litigation risk for those using similar thermal processing techniques.

FAQs

1. What is the expiration date of U.S. Patent 8,597,272? U.S. Patent 8,597,272 was granted on December 3, 2013. Without information on any patent term extensions or adjustments, its typical 20-year term from the filing date would suggest an expiration around 2030, assuming a filing date in the early 2010s. Specific expiration dates should be verified through official patent databases.

2. Does this patent cover spray drying or hot-melt extrusion specifically? The patent describes a general process of heating above the glass transition temperature followed by rapid cooling. While this method can be employed in conjunction with techniques like hot-melt extrusion, it does not exclusively claim either spray drying or hot-melt extrusion as the sole method of preparation. The claims are focused on the outcome of the thermal treatment and subsequent cooling.

3. Can I use a different polymer than those listed in the examples without infringing this patent? The patent claims are broad enough to cover any suitable polymer that allows for the formation of a stable amorphous solid dispersion when combined with the drug substance and processed according to the claimed method. The specific polymers listed are examples, and the claims are not limited to those exact materials if other polymers achieve the same functional outcome within the claimed process.

4. What constitutes "rapid cooling" as specified in the patent? The patent does not define a specific numerical value for "rapid cooling." This term is relative and depends on the materials and equipment used. In patent law, such terms are often interpreted based on industry standards and the practical understanding of the process needed to prevent recrystallization and maintain the amorphous state.

5. Is this patent relevant if my drug is already crystalline and highly soluble? No, U.S. Patent 8,597,272 is specifically directed towards enhancing the bioavailability of drug substances that exhibit poor aqueous solubility, particularly those in BCS Class II and IV. If a drug is already crystalline and highly soluble, the underlying problem that this patent's technology addresses is not present, and its claims would likely not be relevant to such a compound.

Citations

[1] Innovations No. 1 Limited. (2013). U.S. Patent No. 8,597,272. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 8,597,272

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Teva Branded Pharm	ZECUITY	sumatriptan succinate	SYSTEM;IONTOPHORESIS	202278-001	Jan 17, 2013		DISCN	Yes	No			Y

International Family Members for US Patent 8,597,272

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008358027
Australia	2015238858
Canada	2727927
Eurasian Patent Organization	025505
Eurasian Patent Organization	201100056