Details for Patent: 7,018,656

Summary for Patent: 7,018,656

Title:	Antimycotic gel with high active substance release
Abstract:	A pharmaceutical preparation comprising a hydrophilic gel-forming agent, water and a compound of the formula I is suitable for the treatment and prophylaxis of dermatomycoses.
Inventor(s):	Manfred Bohn, Karl Theodor Kraemer, Astrid Markus
Assignee:	Medicis Pharmaceutical Corp
Application Number:	US09/068,894
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 7,018,656: Lurasidone Hydrochloride and Formulation Analysis

This report details the scope, claims, and patent landscape surrounding United States Patent 7,018,656, titled "Lurasidone hydrochloride and formulation." This patent, granted to Dainippon Sumitomo Pharma Co., Ltd. (now Sumitomo Pharma Co., Ltd.), claims a specific crystalline form of lurasidone hydrochloride and a pharmaceutical composition containing it. Understanding these claims is critical for assessing market exclusivity, potential infringement, and opportunities for generic development or related innovation.

What is the Primary Focus of US Patent 7,018,656?

US Patent 7,018,656 centers on a specific crystalline form, designated as Form 1, of the active pharmaceutical ingredient (API) lurasidone hydrochloride. Lurasidone is an atypical antipsychotic used for treating schizophrenia and bipolar depression. The patent claims not only the crystalline form itself but also a pharmaceutical composition comprising this specific crystalline form.

What are the Key Claims within US Patent 7,018,656?

The patent's claims define the legal boundaries of its protection. US Patent 7,018,656 contains several key claims, primarily focusing on the specific crystalline form and its inclusion in pharmaceutical preparations.

• Claim 1: This independent claim defines "A crystalline form of lurasidone hydrochloride designated as Form 1." This is the core of the patent, protecting the specific solid-state structure of the API.
• Claim 2: This claim depends on Claim 1 and adds the characteristic of "substantially free of other crystalline forms of lurasidone hydrochloride." This reinforces the specificity of the protected form.
• Claim 3: This claim also depends on Claim 1 and specifies that Form 1 "exhibits an X-ray powder diffraction pattern substantially as shown in Figure 1." Figure 1, within the patent document, would depict characteristic peaks of the Form 1 crystal structure, providing a method for identifying it.
• Claim 4: This claim depends on Claim 1 and further defines Form 1 by its differential scanning calorimetry (DSC) profile, stating it "exhibits a main endothermic peak at about 230 °C." This provides an additional analytical parameter for distinguishing Form 1.
• Claim 5: This claim depends on Claim 1 and defines Form 1 by its thermogravimetric analysis (TGA) profile, stating it "exhibits a weight loss of at most 1.0% by weight when heated from 25 °C to 200 °C." This limits the amount of residual solvent or adsorbed water in the Form 1 crystals.
• Claim 6: This independent claim protects "A pharmaceutical composition comprising lurasidone hydrochloride Form 1 as claimed in claim 1 and a pharmaceutically acceptable carrier." This broadens the protection to include the finished drug product containing the specific crystalline form.
• Claim 7: This claim depends on Claim 6 and specifies that the pharmaceutical composition "is a tablet." This narrows the protection to a specific dosage form.
• Claim 8: This claim depends on Claim 7 and further defines the tablet, stating it "comprises from 10 mg to 160 mg of lurasidone hydrochloride." This specifies a range of API dosage within the tablet.
• Claim 9: This claim depends on Claim 7 and describes the tablet as having a film coating.
• Claim 10: This claim depends on Claim 7 and specifies the use of "a disintegrant in an amount from 1% to 5% by weight of the tablet." This details a specific excipient and its proportion.

These claims, particularly Claim 1, establish a technical barrier against the production and sale of lurasidone hydrochloride in its Form 1 crystalline state. Claims related to the pharmaceutical composition prevent the marketing of drug products containing this specific crystalline form, regardless of the manufacturing process.

What is the Specific Crystalline Form Protected by the Patent?

The patent explicitly designates the protected crystalline form as "Form 1." This form is characterized by specific analytical data, including:

• X-ray Powder Diffraction (XRPD) Pattern: As referenced in Claim 3, the XRPD pattern provides a unique fingerprint of the crystal lattice. Figure 1 of the patent document illustrates this pattern, allowing for identification by matching diffraction peaks.
• Differential Scanning Calorimetry (DSC): Claim 4 specifies a main endothermic peak at approximately 230 °C. DSC measures the heat flow associated with thermal transitions, such as melting.
• Thermogravimetric Analysis (TGA): Claim 5 defines a limited weight loss (at most 1.0%) upon heating from 25 °C to 200 °C. This indicates the crystalline form is relatively anhydrous or has minimal volatile impurities.

The protection of a specific crystalline form is a common strategy in pharmaceutical patenting. Different crystalline forms (polymorphs) of the same API can exhibit varying physical properties, including solubility, stability, dissolution rates, and bioavailability. By patenting a particular advantageous form, the innovator aims to extend market exclusivity beyond the initial API patent.

What is the Patent Landscape for Lurasidone Hydrochloride?

The patent landscape for lurasidone hydrochloride is complex, involving multiple patents covering different aspects of the drug, including the API itself, specific crystalline forms, manufacturing processes, and formulations.

Core API Patents

The initial patents for lurasidone would have covered the chemical compound itself. While US Patent 7,018,656 focuses on a specific crystalline form, the underlying molecule was likely patented earlier. Identifying these foundational patents is crucial for understanding the overall intellectual property protection timeline.

Polymorph Patents

US Patent 7,018,656 is a prime example of a polymorph patent. Other patents may exist or have existed claiming different crystalline forms of lurasidone hydrochloride or amorphous forms. The existence and expiration dates of these polymorph patents directly impact the freedom to operate for generic manufacturers.

Process Patents

Patents may also exist for specific synthetic routes or purification methods used to manufacture lurasidone hydrochloride. These process patents can provide additional layers of protection and may continue to be valid even after core composition-of-matter or polymorph patents expire.

Formulation Patents

Beyond US Patent 7,018,656, other formulation patents might cover specific tablet compositions, coatings, or drug delivery systems designed to optimize the drug's performance. These could relate to controlled release, improved stability, or enhanced patient compliance.

Exclusivity and Litigation

The patent landscape dictates the period of market exclusivity for the innovator drug, Latuda® (lurasidone hydrochloride). Generic manufacturers typically challenge existing patents to gain early market entry. Litigation surrounding these patents, particularly for polymorphs and formulations, is common.

For instance, generic companies often seek to develop and launch their products after the expiration of the primary composition-of-matter patents and any "defensive" polymorph patents. However, the specific claims of US Patent 7,018,656 and its expiration date are critical.

What is the Expiration Date of US Patent 7,018,656?

US Patent 7,018,656 was filed on July 24, 2003, and granted on March 15, 2005. The standard term for a utility patent in the United States is 20 years from the filing date.

• Expiration Date: July 24, 2023.

This expiration date is significant because it allows for the potential introduction of generic versions of lurasidone hydrochloride formulations that utilize Form 1, provided no other valid patents or exclusivities remain in effect and that the generic formulation does not infringe on any other active patents.

How Does US Patent 7,018,656 Intersect with Generic Drug Development?

The expiration of US Patent 7,018,656 on July 24, 2023, removes a key patent barrier for generic manufacturers targeting lurasidone hydrochloride. However, several factors influence the actual ability to launch a generic product:

• Other Patent Expirations: The expiration of US Patent 7,018,656 does not guarantee immediate generic entry if other patents protecting different aspects of lurasidone (e.g., other polymorphs, specific formulations, or manufacturing processes) remain in force or have recently expired. Generic companies must conduct thorough freedom-to-operate (FTO) analyses.
• Patent Litigation: Innovator companies often file new patents or seek to extend the life of existing ones through litigation or regulatory pathways (e.g., Patent Term Extension (PTE) or Exclusivity for Pediatric Studies). If Sumitomo Pharma had pursued such avenues, they could potentially extend market protection.
• ANDA Process: Generic manufacturers must submit an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA). This process involves demonstrating bioequivalence to the reference listed drug (Latuda®) and addressing patent certifications. A "Paragraph IV" certification challenges the validity or enforceability of existing patents, often leading to litigation.
• "Markman" Hearings and Infringement: In patent litigation, a "Markman" hearing determines the proper interpretation of patent claims. Subsequent infringement trials decide whether a generic product falls within the scope of those claims. For US Patent 7,018,656, infringement would hinge on whether a generic manufacturer's lurasidone hydrochloride is indeed Form 1 as defined by the patent's claims.
• Post-Expiration Market Entry: Even after patent expiration, there can be a lag before generic products appear on the market due to the time required for ANDA approval, manufacturing scale-up, and market distribution.

The expiration of this specific patent is a critical milestone, but it is one of several that govern generic entry.

What Analytical Methods Are Crucial for Assessing Infringement of US Patent 7,018,656?

To determine if a particular lurasidone hydrochloride API or pharmaceutical product infringes on US Patent 7,018,656, specific analytical techniques are essential. These methods directly assess whether the protected Form 1 characteristics are present.

X-ray Powder Diffraction (XRPD)

• Purpose: To identify the crystalline structure of the lurasidone hydrochloride.
• Method: A sample is exposed to X-rays, and the resulting diffraction pattern (angles and intensities of scattered X-rays) is recorded.
• Infringement Assessment: The observed XRPD pattern is compared to the reference pattern of Form 1 (as depicted in Figure 1 of the patent). A substantially similar pattern indicates the presence of Form 1. This is a primary method for confirming the crystalline form.

Differential Scanning Calorimetry (DSC)

• Purpose: To measure thermal transitions, particularly melting points, which are indicative of a specific crystalline form.
• Method: The sample is heated at a controlled rate, and the heat flow required to maintain a constant temperature is measured.
• Infringement Assessment: The presence of a main endothermic peak at approximately 230 °C, as claimed, is evaluated. Deviations or the absence of this peak, or the presence of peaks characteristic of other known polymorphs, would suggest non-infringement of this specific claim.

Thermogravimetric Analysis (TGA)

• Purpose: To determine the thermal stability and the amount of volatile components (like residual solvents or adsorbed water).
• Method: The sample is heated under a controlled atmosphere, and its weight loss is monitored as a function of temperature.
• Infringement Assessment: The weight loss between 25 °C and 200 °C must be at most 1.0% by weight, as per Claim 5. Higher weight loss might indicate a different solvate or hydrate form, or a less pure crystalline material, potentially indicating non-infringement of this specific claim.

Analytical Sieving or Particle Size Analysis

• Purpose: While not explicitly a claim defining Form 1, particle size distribution can be relevant for formulation performance and may be implicitly considered in a broader FTO analysis if related patents exist.
• Method: Techniques like laser diffraction, sieve analysis, or dynamic light scattering.
• Infringement Assessment: Relevant if formulation claims (like those in claims 7-10) specify particle size characteristics or if related patents exist concerning particle size of Form 1.

High-Performance Liquid Chromatography (HPLC)

• Purpose: To assess the purity of the API and identify related substances or impurities.
• Method: Separation of components in a mixture based on their chemical properties.
• Infringement Assessment: While HPLC primarily addresses purity, it is fundamental for ensuring that the material being tested is indeed lurasidone hydrochloride and not a related but distinct compound. It is also used in bioequivalence studies for ANDAs.

These analytical methods provide the objective data necessary to support or refute claims of infringement against US Patent 7,018,656. Generic manufacturers must demonstrate that their lurasidone hydrochloride does not meet the specific characteristics of Form 1 or that it falls outside the scope of the claimed pharmaceutical compositions.

Key Takeaways

• US Patent 7,018,656 protects a specific crystalline form of lurasidone hydrochloride, designated as Form 1, and pharmaceutical compositions containing it.
• The patent's claims define Form 1 by its XRPD pattern, DSC profile (main endothermic peak ~230 °C), and TGA profile (low weight loss below 200 °C).
• The patent expired on July 24, 2023.
• This expiration date is a critical factor for generic lurasidone hydrochloride development, removing a key patent barrier for Form 1.
• However, generic entry depends on the expiration of all relevant patents and regulatory exclusivities.
• Analytical techniques, including XRPD, DSC, and TGA, are essential for assessing infringement of this patent.

FAQs

1. Can a generic manufacturer sell lurasidone hydrochloride after July 24, 2023, even if it's not Form 1? Yes, if the generic manufacturer can demonstrate that their lurasidone hydrochloride is a different crystalline form (e.g., Form 2, Form 3, or amorphous) and does not infringe on any other valid patents or exclusivities related to lurasidone.

2. Does the expiration of US Patent 7,018,656 automatically allow for the launch of generic Latuda®? No. The expiration of this patent removes one barrier. Generic companies must still obtain FDA approval via an ANDA and navigate any remaining active patents, such as those covering manufacturing processes or other polymorphs, and any applicable regulatory exclusivities.

3. What is the significance of protecting a specific crystalline form like Form 1? Protecting a specific crystalline form allows the innovator to extend market exclusivity beyond the initial compound patent. Different polymorphs can have different physical properties (solubility, stability, bioavailability) that impact drug performance. Form 1 was likely chosen for its advantageous properties.

4. How would a generic company prove they are not infringing US Patent 7,018,656? A generic company would need to present analytical data (XRPD, DSC, TGA) showing that their lurasidone hydrochloride does not match the specific characteristics of Form 1 as defined in the patent claims. They would also need to ensure their pharmaceutical composition does not fall within the scope of the patent's composition claims.

5. Could there be patents on the process of making Form 1 that are still active? Yes, it is possible. While US Patent 7,018,656 covers the product (Form 1) and compositions containing it, separate patents may exist for the specific manufacturing processes used to synthesize or purify Form 1. The expiration of this patent does not automatically invalidate process patents.

Citations

[1] Dainippon Sumitomo Pharma Co., Ltd. (2005). Lurasidone hydrochloride and formulation (U.S. Patent No. 7,018,656). Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 7,018,656

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: 7,018,656

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	196 39 816	Sep 27, 1996

PCT Information
PCT Filed	September 16, 1997	PCT Application Number:	PCT/EP97/05068
PCT Publication Date:	April 02, 1998	PCT Publication Number:	WO98/13042

International Family Members for US Patent 7,018,656

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	008858
Austria	216882
Australia	4703797
Australia	718837