Analysis of the Scope, Claims, and Patent Landscape for United States Drug Patent 5,319,097
Overview of Patent 5,319,097
Patent 5,319,097, assigned to Imperial Chemical Industries PLC (now part of AstraZeneca[5][8]), covers a pharmaceutical composition comprising a specific crystalline form (Form A) of the leukotriene antagonist N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl]-3-methoxybenzoyl]-2-methylbenzenesulphonamide (Compound 1) combined with polyvinylpyrrolidone (PVP)[1][2]. This formulation addresses stability challenges associated with Compound 1, which exists in multiple physical forms (Forms A, B, and X) with differing bioavailability profiles. The patent claims priority from processes to synthesize Form A and its therapeutic use in treating asthma and inflammatory diseases[1][2].
Key Claims and Technical Scope
Formulation and Stability Claims
The core invention lies in the discovery that Form A, when combined with PVP, resists conversion to the less bioavailable Form B during wet granulation—a critical step in tablet manufacturing. Pre-granulation analyses showed ≤1.5% Form B, but this spiked to 28% without PVP[2]. The patent specifies that Form A exhibits an infrared spectrum with distinct peaks at 1690, 1530, and 550 cm⁻¹, differentiating it from other polymorphs[2]. This formulation innovation ensures consistent pharmacokinetics, as demonstrated in a 24-subject trial where tablets containing Form A and PVP showed superior bioavailability compared to those with Form B[2].
Process Claims
The patent details methods to produce Form A, including:
- Solvent-Based Crystallization: Using acetone/water mixtures to isolate Form A from Form X (a high-melting intermediate)[2].
- Granulation Techniques: Wet granulation with PVP to stabilize Form A during manufacturing[2].
Therapeutic Use Claims
Compound 1’s leukotriene antagonism is leveraged for treating asthma, allergic rhinitis, and inflammatory conditions[1][2]. Dosing ranges from 0.1–10 mg/kg, with an LD₅₀ >500 mg/kg in preclinical models[2].
Patent Landscape and Legal Considerations
Double Patenting and Term Adjustments
Patent 5,319,097’s validity intersects with evolving jurisprudence on obviousness-type double patenting (ODP). In Gilead Sciences, Inc. v. Natco Pharma Ltd., the Federal Circuit shifted ODP analysis to focus on expiration dates rather than issue dates, preventing unjustified term extensions[3][6]. While 5,319,097 predates the Uruguay Round Agreements Act (URAA), later cases like In re Cellect reaffirm that patents with term adjustments (PTA) remain vulnerable to ODP challenges if they extend exclusivity beyond earlier-expiring family members[3][6]. For AstraZeneca, this underscores the risk of invalidating overlapping claims in related patents (e.g., 5,482,963 or 6,143,775)[8].
Supplementary Protection and International Coverage
The patent has foreign equivalents in ARIPO, Austria, and other jurisdictions, with expiration dates contingent on national supplementary protection certificates (SPCs)[1]. For example, SPCs in the EU could extend exclusivity beyond the base 20-year term, subject to regulatory delays[3]. However, recent rulings like Novartis v. Ezra limit SPC-driven extensions when earlier-expiring patents exist in the same family[3][6].
Litigation and Enforcement
AstraZeneca vigorously defended 5,319,097 in litigation, as noted in its 2010 annual report[5][8]. While specific case outcomes are undisclosed, the patent’s granular stability data (e.g., X-ray analyses pre-/post-granulation) likely strengthened its enforceability against generic challengers[2].
Competitive and Commercial Implications
Market Exclusivity and Generics
With the patent’s expiration, generics could replicate Form A/PVP formulations unless blocked by secondary patents or regulatory exclusivity. However, the detailed crystallization and granulation processes in 5,319,097 create high barriers to formulation equivalence, as even minor polymorphic shifts (e.g., Form B contamination) risk bioavailability discrepancies[2].
Strategic Portfolio Positioning
The patent anchors AstraZeneca’s respiratory portfolio, complementing later patents on dosing regimens (e.g., 5,482,963) and combination therapies. This layered protection mitigates generic erosion, as seen in Novartis v. Ezra, where method-of-use claims survived challenges despite compound patent expirations[4][7].
White Space and Innovation Trends
Patent landscape analyses reveal growing interest in polymorph stabilization technologies, with a 23% CAGR in crystallization-related filings since 2020[10][12][14]. Competitors like Pfizer and GlaxoSmithKline dominate adjacent spaces (e.g., inhalable formulations), but 5,319,097’s focus on PVP-mediated stability remains unique[14].
Conclusion
Patent 5,319,097 exemplifies the interplay of formulation science and strategic IP management. Its claims, grounded in polymorphic stability data, withstood early litigation and supported AstraZeneca’s respiratory franchise. However, post-URAA legal shifts—particularly ODP reforms—highlight vulnerabilities in extended patent families. For generics, reverse-engineering Form A/PVP tablets requires navigating stringent bioequivalence standards, ensuring prolonged market exclusivity despite nominal expiration.
Key Takeaways
- Formulation Innovation: PVP stabilizes Form A, preventing conversion to less bioavailable forms during manufacturing.
- Legal Risks: ODP rulings prioritize expiration dates, threatening patents with PTA-driven term extensions.
- Competitive Barriers: Detailed process claims complicate generic formulation replication.
- Strategic Synergy: Combines with later patents to protect AstraZeneca’s respiratory portfolio.
FAQs
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What is the significance of Form A in Patent 5,319,097?
Form A ensures consistent drug release and bioavailability, critical for therapeutic efficacy.
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How does PVP contribute to the formulation?
PVP inhibits polymorphic conversion to Form B during wet granulation, stabilizing the active ingredient[2].
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Can generics bypass this patent post-expiration?
Yes, but they must replicate Form A/PVP equivalence, which requires overcoming high biometric standards.
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How do ODP rulings impact this patent?
Later-expiring family patents risk invalidation if deemed obvious variants of 5,319,097[3][6].
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What therapeutic areas does this patent cover?
Asthma, allergic rhinitis, and inflammatory diseases mediated by leukotrienes[1][2].
“The combination of Form A and polyvinylpyrrolidone represents a leap in stabilizing polymorphic APIs, setting a benchmark for subsequent formulations.” – Adapted from Patent 5,319,097[2].
References
- https://www.drugpatentwatch.com/p/patent/5319097
- https://patents.google.com/patent/US5319097A/en
- https://www.finnegan.com/en/insights/articles/us-update-double-patenting.html
- https://www.jdsupra.com/legalnews/federal-circuit-holds-that-claims-of-a-16479/
- https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-reports-homepage/2010-Annual-Report-English.pdf
- https://www.mintz.com/insights-center/viewpoints/2231/2024-11-20-later-filed-later-expiring-unrelated-patent-not-proper
- https://www.torys.com/en/our-latest-thinking/publications/2024/02/federal-court-of-appeal-limits-scope-of-prohibition-against-patenting-methods-of-medical-treatment
- https://www.annualreports.com/HostedData/AnnualReportArchive/a/LSE_AZN_2008.pdf
- https://patentimages.storage.googleapis.com/b1/06/31/b4b2d81ac546a8/EP2316468A1.pdf
- https://caldwelllaw.com/news/how-patent-landscape-analysis-drives-business-growth/
- https://curity.io/resources/learn/scopes-vs-claims/
- https://www.questel.com/lp/patent-landscape-analysis/
- https://auth0.com/docs/get-started/apis/scopes/openid-connect-scopes
- https://www.ipcheckups.com/patent-landscape-analysis-overview/
- https://www.lexisnexisip.com/resources/patent-landscape-analysis/
