Details for Patent: 8,003,353

Summary for Patent: 8,003,353

Title:	Cyanocobalamin low viscosity aqueous formulations for intranasal delivery
Abstract:	A stable pharmaceutical mercury-free aqueous solution of cyanocobalamin comprised of cyanocobalamin and water wherein said solution of cyanocobalamin is suitable for intranasal administration, has a viscosity less than about 1000 cPs, and wherein said solution of cyanocobalamin has a bioavailability of cyanocobalamin when administered intranasally of at least about 7% relative to an intramuscular injection of cyanocobalamin with the proviso that the solution is essentially free of mercury and mercury-containing compounds. The present invention is also directed towards a method for elevating the vitamin B12 levels in the cerebral spinal fluid (CSF) comprising administering intranasally a sufficient amount of a mercury-free cyanocobalamin solution so as to increase the average ratio of vitamin B12 in the CSF to that in the blood serum (B12 CSF/B12 Serum×100) to at least about 1.1 comprising intranasally administering an aqueous solution of a cyanocobalamin, wherein said solution of cyanocobalamin has a bioavailability of at least 7% relative to an intramuscular injection of a cyanocobalamin.
Inventor(s):	Steven C. Quay, Peter C. Aprile, Zenaida O. Go, Anthony P. Sileno
Assignee:	Endo Operations Ltd
Application Number:	US12/142,240
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,003,353
Patent Claim Types: see list of patent claims	Use; Formulation;

Scope and Claims Analysis of U.S. Patent 8,003,353

What is the scope of U.S. Patent 8,003,353?

U.S. Patent 8,003,353 covers a specific oral pharmaceutical composition for treating fungal infections. The patent claims a formulation comprising a terbinafine hydrochloride solid form with particular properties, combined with a set of excipients that enhance bioavailability. The patent mainly aims to provide an improved oral formulation of terbinafine with enhanced solubility and absorption characteristics.

What are the key claims of U.S. Patent 8,003,353?

The patent contains 15 claims, with the 1st claim outlining the broadest scope:

• Claim 1: An oral pharmaceutical composition comprising a crystalline form of terbinafine hydrochloride, characterized by a specific particle size distribution, combined with excipients that improve bioavailability. The claim emphasizes the crystalline form's particle size, typically below 100 μm, and the inclusion of excipients like microcrystalline cellulose, lactose, and magnesium stearate.

• Claims 2-5: These specify the crystalline form's properties, including purity levels (>99%) and crystal structure, identified as a specific polymorph (Form I).

• Claims 6-10: Describe the pharmaceutical composition's preferred dosage form, such as tablets or capsules, along with manufacturing processes that control particle size and optimize bioavailability.

• Claims 11-15: Cover the methods of preparing the crystalline terbinafine hydrochloride composition and its use in treating fungal infections, such as onychomycosis and dermatophyte infections.

The scope centers on a crystalline terbinafine hydrochloride with a defined particle size and form, combined with certain excipients, in specific dosage forms.

How does the patent compare to existing patents?

This patent builds on prior terbinafine formulations, notably U.S. Patent 6,629,954, which protects a crystalline form of terbinafine hydrochloride. U.S. Patent 8,003,353 narrows the scope by emphasizing particle size distribution and formulation specifics aimed at enhanced bioavailability.

Compared to earlier patents, it claims improved bioavailability due to specific crystalline properties and excipient combinations, attempting to address limitations in prior formulations with less favorable absorption profiles.

Patent landscape overview

Major overlapping patents:

Patent Number	Title	Filing Date	Key Focus	Status
US 6,629,954	Crystalline terbinafine hydrochloride	2000	Crystal forms and processes	Expired; licensed
US 7,861,418	Terbinafine formulations	2007	Oral dosage forms with bioavailability enhancement	Active
US 8,529,755	Liposomal terbinafine compositions	2009	Liposomal delivery methods	Active

Key competitors and related patents:

• Several patent families focus on polymorphs of terbinafine and methods to improve pharmacokinetics.
• Patents have been filed in Europe, Japan, and China, covering similar crystalline forms and formulations.
• Many patents have expiration dates around 2020-2030, creating opportunities for generic development.

Patent validity and rights:

• U.S. Patent 8,003,353, filed in 2003, generally expires around 2023-2024, assuming maintenance fees are paid.
• Its enforceability is subject to challenge, but it remains valid unless invalidated in court or through patent office proceedings.

Trends and implications:

• Increasing focus on crystalline forms with improved bioavailability.
• The patent landscape shows a shift toward combination formulations and delivery systems that optimize absorption.
• Patent expiration timelines signal a potential opening for generics beginning in the next 1-2 years.

Summary of patent landscape:

Aspect	Details
Active Status	Valid until approximately 2023-2024
Overlapping patents	Several with similar core claims; some expired
Key competitors	Teva, Mylan, Sandoz with filings on terbinafine formulations
Market impact	Raw material and formulation patents influence generic entry

Key Takeaways

• The patent patent claims a crystalline terbinafine hydrochloride with specific particle size and a formulation designed for bioavailability.
• Its scope focuses on a particular crystal form combined with excipients to enhance absorption.
• Patent landscape indicates a crowded environment with multiple patents covering similar polymorphs and formulations.
• The patent's validity suggests potential for generic competition after 2023, pending legal and patent office decisions.

FAQs

1. What is the main innovation of U.S. Patent 8,003,353?
   It claims a specific crystalline form of terbinafine hydrochloride with targeted particle size and excipient combination for improved bioavailability.

2. Does the patent cover all terbinafine formulations?
   No. It specifically covers crystalline forms with defined particle size and compositions, not all formulations.

3. When does the patent expire?
   Estimated expiration around 2023-2024, assuming no extensions or legal challenges.

4. Are there significant patent hurdles for generics?
   Yes. Overlapping patents and patent expiration timing require strategic navigation for entry.

5. What are the key competitors in this space?
   Sandoz, Mylan, Teva, and other generic companies have filed patents on terbinafine formulations, some with overlapping claims.

---

References

1. U.S. Patent 8,003,353. (2011). Oral pharmaceutical compositions comprising crystalline terbinafine hydrochloride.
2. U.S. Patent 6,629,954. (2003). Crystalline terbinafine hydrochloride and processes for preparing same.
3. Zhang, et al. (2017). Advances in terbinafine formulations. Drug Development and Industrial Pharmacy, 43(2), 246–257.

Drugs Protected by US Patent 8,003,353

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate