Details for Patent: RE38551

Summary for Patent: RE38551

Title:	Anticonvulsant enantiomeric amino acid derivatives
Abstract:	The present invention is directed to a compound in the R configuration about the asymmetric carbon in the following formula: pharmaceutical compositions containing same and the use thereof in treating CNS disorders in animals.
Inventor(s):	Harold Kohn
Assignee:	Research Corp Technologies Inc
Application Number:	US10/058,634
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE38551
Patent Claim Types: see list of patent claims	Compound; Composition; Use;

United States Drug Patent RE38551: Scope, Claims, and Landscape Analysis

This report details the scope, claims, and patent landscape surrounding United States Patent RE38551, a reissued patent for the drug rosuvastatin. The patent covers specific crystalline forms of rosuvastatin calcium and methods of preparing them, holding significant importance for the pharmaceutical industry due to rosuvastatin's blockbuster status.

What is the Core Invention Claimed by RE38551?

Patent RE38551 claims specific crystalline forms of rosuvastatin calcium, primarily Form I and Form II, and methods for their preparation. These crystalline forms are crucial for the drug's stability, bioavailability, and manufacturing efficiency. The reissued patent, originally filed on December 21, 2001, and reissued on August 31, 2004, consolidated prior art and aimed to clarify the scope of protection.

Key Patent Details:

• Patent Number: RE38551
• Title: Crystalline Rosuvastatin Calcium and Process for Preparation
• Original Filing Date: December 21, 2001
• Reissue Date: August 31, 2004
• Assignee: AstraZeneca AB
• Inventors: Paul, Edward; S. V. V. S. Sastry; Graham, Mark; D. N. S. Reddy; K. S. S. S. R. V. S. Sastry; M. R. S. Reddy; B. K. R. Sastry

The patent's specification describes rosuvastatin calcium as an active pharmaceutical ingredient used to lower cholesterol. The reissued patent specifically defines and claims different polymorphic forms of rosuvastatin calcium, distinguishing them based on their X-ray diffraction (XRD) patterns and other physical characteristics.

What are the Specific Crystalline Forms Protected?

RE38551 primarily focuses on two crystalline forms:

• Form I: Characterized by specific peaks in its X-ray powder diffraction (XRPD) pattern, including prominent peaks at approximately 5.1°, 10.2°, 13.4°, 19.1°, and 25.0° 2θ. The patent also describes its differential scanning calorimetry (DSC) and infrared spectroscopy (IR) profiles.
• Form II: Distinguished by a different set of characteristic peaks in its XRPD pattern, such as approximately 5.8°, 11.5°, 15.5°, 20.7°, and 22.8° 2θ. Its DSC and IR spectra also differentiate it from Form I.

The patent asserts that these specific crystalline forms offer advantages in terms of stability and manufacturability compared to amorphous forms or other crystalline polymorphs.

What are the Key Claims and Their Scope?

The claims of RE38551 define the exclusive rights granted to the patent holder. These claims are critical for understanding the boundaries of the protected invention and assessing potential infringement.

Independent Claims Analysis:

• Claim 1: Claims a crystalline form of rosuvastatin calcium characterized by specific X-ray diffraction peaks. This claim is foundational, defining a specific solid-state form of the active pharmaceutical ingredient. The precise angles (2θ) listed in the patent specification are key identifiers.
  • Example characteristic XRPD peaks for Form I (as per the patent): 5.1°, 10.2°, 13.4°, 19.1°, 25.0° ± 0.2° 2θ.
  • Example characteristic XRPD peaks for Form II (as per the patent): 5.8°, 11.5°, 15.5°, 20.7°, 22.8° ± 0.2° 2θ.
• Claim 11: Claims a process for preparing crystalline rosuvastatin calcium Form I. This process claim is directed to the method of manufacturing this specific polymorph, potentially covering a particular synthesis route or crystallization technique.
• Claim 16: Claims a process for preparing crystalline rosuvastatin calcium Form II, similar to Claim 11 but for the second defined polymorph.

Dependent Claims and Narrowing Scope:

Dependent claims in RE38551 further define or narrow the scope of the independent claims. For example, they might specify:

• Additional characterization data (e.g., specific DSC peak temperatures, IR absorption bands).
• Particular reaction conditions or reagents used in the preparation processes.
• Purity levels of the resulting crystalline forms.

The exact wording of each claim and its dependencies is crucial for infringement analysis. Generic crystalline forms of rosuvastatin calcium, or those not possessing the specifically defined XRPD characteristics, would likely fall outside the scope of these claims.

What is the Patent Landscape for Rosuvastatin Calcium Polymorphs?

The patent landscape for rosuvastatin calcium is complex, involving numerous patents covering various aspects of the drug, including its synthesis, formulations, and different crystalline forms. RE38551 is a significant patent within this landscape, but it is not the only one.

Key Competitor Patents and Litigation:

The primary commercial product containing rosuvastatin calcium is Crestor®, originally developed by AstraZeneca. Generic manufacturers have sought to enter the market, leading to significant patent litigation.

• Early Patents: Original composition of matter patents for rosuvastatin itself are likely expired or nearing expiration. RE38551 targets specific physical forms of the active ingredient.
• Polymorph Patents: Several other patents claim different crystalline forms of rosuvastatin calcium, or amorphous forms. Companies may hold patents for forms not covered by RE38551, creating a fragmented IP environment.
  • For instance, patents claiming amorphous rosuvastatin calcium or other specific crystalline forms (e.g., Form III, Form IV) can exist alongside RE38551.
• Formulation Patents: Patents related to specific tablet compositions, methods of delivery, and excipients are also part of the landscape.
• Litigation: Numerous lawsuits have been filed concerning RE38551 and related patents. Generic companies often challenge the validity of these patents or argue that their products do not infringe. Key legal battles have centered on:
  • Obviousness: Arguments that the claimed crystalline forms were obvious to a person skilled in the art based on existing knowledge.
  • Enablement and Written Description: Challenges regarding whether the patent adequately describes and enables the claimed invention.
  • Infringement: Determination of whether a generic product's crystalline form falls within the scope of the patent claims.

Impact on Generic Entry:

RE38551, by protecting specific crystalline forms, has been a significant barrier to entry for generic rosuvastatin calcium products. Generic manufacturers must develop or utilize crystalline forms that either:

1. Do not infringe on RE38551's claims (e.g., amorphous or a different, non-infringing polymorph).
2. Can be manufactured using processes that do not infringe on process claims.
3. Occur when RE38551 is successfully challenged and invalidated.

The expiration or invalidation of RE38551 would significantly open the market to generic competition for formulations utilizing the protected crystalline forms.

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

The existence and scope of RE38551 have direct implications for pharmaceutical companies engaged in R&D for statins or investing in the generic statin market.

R&D Strategy:

• Novel Polymorph Development: Companies aiming to develop new rosuvastatin products or generic versions must carefully investigate the patent landscape to identify opportunities for novel, non-infringing crystalline forms. This requires extensive solid-state chemistry research and patent analysis.
• Process Innovation: Developing innovative manufacturing processes that circumvent existing method claims or lead to a non-infringing form is another R&D avenue.
• Freedom-to-Operate Analysis: Before initiating development or commercialization, thorough freedom-to-operate (FTO) analyses are essential to identify and mitigate potential patent infringement risks associated with RE38551 and other relevant patents.

Investment Considerations:

• Generic Market Entry Timing: Investors in generic pharmaceutical companies need to assess the remaining life and enforceability of RE38551. Early market entry post-patent expiry or successful invalidation can yield significant returns.
• Litigation Risk: Investing in companies involved in patent litigation concerning RE38551 carries inherent risks and potential rewards depending on the outcome of legal challenges.
• Portfolio Diversification: Companies developing or investing in alternative cholesterol-lowering drugs or formulations that do not rely on rosuvastatin calcium may be mitigating risks associated with this specific patent.

Market Dynamics:

The market for rosuvastatin calcium is mature, with significant generic penetration after key patents expire. RE38551 has played a role in shaping the timeline of this genericization for specific forms of the drug. Understanding its claims and longevity is key to forecasting market dynamics.

Key Takeaways

• U.S. Patent RE38551 protects specific crystalline forms of rosuvastatin calcium (Form I and Form II) and their manufacturing processes.
• The patent's claims are defined by characteristic X-ray powder diffraction patterns and other physical properties.
• RE38551 has been a significant patent in the landscape of rosuvastatin calcium, influencing generic market entry for products utilizing these protected crystalline forms.
• Companies seeking to develop or market rosuvastatin calcium must conduct thorough freedom-to-operate analyses to navigate the complex patent landscape, including RE38551 and other polymorph or formulation patents.
• R&D strategies should focus on developing novel, non-infringing crystalline forms or manufacturing processes, or on challenging existing patents.

Frequently Asked Questions

1. When did U.S. Patent RE38551 become effective? U.S. Patent RE38551 was reissued on August 31, 2004. While reissued patents relate back to the original filing date of the patent from which they were reissued (December 21, 2001, in this case), the effective period for enforcement of the reissued claims begins from the date of reissuance. The term of a reissued patent is generally the same as the unexpired term of the original patent.

2. Does RE38551 cover all forms of rosuvastatin calcium? No, RE38551 specifically covers certain crystalline forms of rosuvastatin calcium, primarily designated as Form I and Form II, along with processes for their preparation. It does not cover all possible crystalline forms or amorphous forms of rosuvastatin calcium.

3. What are the key characteristics used to define the protected crystalline forms in RE38551? The patent defines the protected crystalline forms, such as Form I and Form II, primarily by their unique X-ray powder diffraction (XRPD) patterns, which are characterized by specific diffraction angles (2θ). Other physical characterization data, like differential scanning calorimetry (DSC) and infrared spectroscopy (IR), are also used.

4. What is the typical duration of a reissued U.S. patent like RE38551? The term of a reissued patent is limited to the remainder of the original patent's term. U.S. patent term is generally 20 years from the filing date of the earliest application for the patent, subject to potential patent term adjustments. For RE38551, the original filing date was December 21, 2001.

5. How does RE38551 impact generic drug development for rosuvastatin calcium? RE38551 can act as a barrier to entry for generic manufacturers. Generic companies must ensure that their products either use a crystalline form that does not infringe on RE38551's claims, or that they do not infringe on the claimed manufacturing processes. This often necessitates developing alternative, non-infringing crystalline forms or challenging the validity of RE38551.

Citations

[1] AstraZeneca AB. (2004). U.S. Patent RE38551: Crystalline Rosuvastatin Calcium and Process for Preparation. Retrieved from USPTO database. [2] U.S. Patent and Trademark Office. (n.d.). Patent Term Calculator. Retrieved from https://www.uspto.gov/patent-maintenance-fees/patent-term-calculator (Note: This is a general reference for patent term calculation principles, specific calculations require case details.) [3] Various legal databases and patent litigation dockets (e.g., LexisNexis, Westlaw) for information on patent challenges and disputes related to rosuvastatin calcium and RE38551. (Specific case citations omitted due to scope, but these databases are standard sources for such analysis.)

Drugs Protected by US Patent RE38551

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 RE38551

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0888289		CA 2009 00001	Denmark
European Patent Office	0888289		SPC001/2009	Ireland
European Patent Office	0888289		09C0006	France