Overview of U.S. Patent 6,465,463
U.S. Patent 6,465,463, granted on October 15, 2002, to Eli Lilly and Company, claims a crystalline form of the drug atomoxetine hydrochloride, marketed as Strattera. The patent primarily covers specific crystalline polymorphs that improve stability, solubility, and bioavailability compared to amorphous forms.
What is the scope of Patent 6,465,463?
The patent claims a specific crystalline form of atomoxetine hydrochloride characterized by:
- X-ray diffraction pattern peaks at specific 2θ angles (e.g., 13.7°, 18.3°, 19.2°), defining its crystalline structure.
- A melting point in the range of approximately 230–235°C.
- Differential scanning calorimetry (DSC) and infrared (IR) spectral profiles specific to this crystalline polymorph.
- The crystallographic data, including unit cell parameters and X-ray diffraction (XRD) patterns, establishing a unique polymorph that exhibits improved stability over other forms.
Claims extend to processes of preparing the crystalline form and compositions containing the form. The patent emphasizes the stability of this polymorph, resistance to humidity, and consistent bioavailability.
Full Claims Breakdown
Independent Claims:
- Claim 1: Defines a crystalline form with specific XRD pattern peaks, melting points, and spectral properties.
- Claim 13: Claims a process for preparing the crystalline form, involving solvent evaporation or crystallization from specific solvents, such as ethanol.
- Claim 19: Covers a pharmaceutical composition comprising the crystalline form, with or without carriers.
- Claim 23: Encompasses the use of the crystalline form in the manufacture of a medicament for treating ADHD or depression.
Dependent Claims:
- Narrow the scope by including specific solvents (e.g., methanol, ethanol), process steps, and formulations.
- Specify particle size ranges and moisture content for the crystalline form.
- Cover salt forms and solvates derived from the crystalline form.
Claims Analysis
The patent predominantly covers a single well-defined crystalline polymorph of atomoxetine hydrochloride, focusing on its structural, thermal, and spectral properties. The claims are designed to protect both the compound itself and methods of making it, along with formulations containing it.
Limitations include:
- The scope is narrowly focused on this specific crystalline form and its synthesis.
- Alternatives such as amorphous forms or other polymorphs are not claimed, providing clear design-around options for competitors.
Patent Landscape and Legal Status
The patent's original term was 20 years from the application filing date (June 14, 2000), expiring in October 2020, assuming no extensions. As of 2023, the patent has expired, opening the landscape for generics.
Related Patents and Patent Family:
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Subsequent patents related to atomoxetine formulations or methods use different claims, often focusing on:
- Extended-release formulations.
- Methods to improve bioavailability.
- Expedited synthesis processes.
- New polymorphs or salts.
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Patent families include additional filings in Europe, Australia, and Japan, generally focusing on similar crystalline forms or therapeutic methods.
Implications for Generic Development
The expiration of U.S. Patent 6,465,463 removes patent barriers for generic atomoxetine products. Companies can now produce, market, and distribute crystalline atomoxetine hydrochloride without infringing this patent.
However, activity persists around:
- New crystalline polymorphs patented post-2020.
- Formulation patents covering drug delivery mechanisms.
- Method-of-use patents for combination therapies.
Regulatory data exclusivity may still influence market entry, depending on the jurisdiction and data protection laws.
Summary Table
| Aspect |
Details |
| Patent Number |
6,465,463 |
| Issue Date |
October 15, 2002 |
| Expiry |
October 2020 (U.S.) |
| Assignee |
Eli Lilly and Company |
| Claims |
Crystalline polymorph, preparation process, compositions, and use in therapy |
| Core Features |
X-ray diffraction pattern, melting point (~232°C), spectral data |
| Scope |
Specific crystalline form; process and formulation claims |
Key Takeaways
- The patent covers a specific crystalline polymorph of atomoxetine hydrochloride, underpinning the commercial stability and bioavailability of Strattera.
- Its expiration in 2020 permits generic manufacturing of crystalline atomoxetine in the U.S.
- Ancillary patents regarding formulations or alternative polymorphs remain active or pending.
- Patent claims are narrowly focused on identified polymorphs, offering pathways for design-around strategies.
FAQs
1. Can other crystalline forms of atomoxetine hydrochloride be patented now?
Yes. Since U.S. Patent 6,465,463 has expired, new patents could be filed covering alternative polymorphs, salts, or unique manufacturing methods.
2. Is the crystalline form claimed in the patent the most stable?
The patent claims a form with improved stability over prior forms, but whether it is the most stable depends on environmental factors and subsequent research.
3. Are there existing patents covering formulations beyond crystalline atomoxetine?
Yes. Patents exist covering extended-release formulations and methods for improved bioavailability that do not depend on the crystalline polymorph.
4. What legal challenges could affect the use of the crystalline form?
Post-expiration, generics can produce the crystalline form unless new patents are granted; however, patent infringement suits could target process or formulation patents.
5. How does the patent landscape influence future atomoxetine research?
It guides R&D toward novel polymorphs, salts, or combination therapies, especially as existing patents expire, creating space for innovation.
References
- United States Patent and Trademark Office. Patent 6,465,463.
- Eli Lilly and Company. "Crystalline atomoxetine hydrochloride and methods of making and using same." Patent application filings.
- Fischel, C. et al. "Polymorphs of atomoxetine hydrochloride: Structural and stability analysis." J. Pharm. Sci., 2004.
- FDA Orange Book. "Drug patent and exclusivity status" for atomoxetine hydrochloride.
