Details for Patent: 6,216,033

Summary for Patent: 6,216,033

Title:	Device for transdermal electrotransport delivery of fentanyl and sufentanil
Abstract:	The invention provides an improved electrotransport drug delivery system for analgesic drugs, namely fentanyl and sufentanil. The fentanyl/sufentanil is provided as a water soluble salt (e.g., fentanyl hydrochloride), preferably in a hydrogel formulation, for use in an electrotransport device (10). In accordance with the present invention, a transdermal electrotransport delivered dose of fentanyl/sufentanil is provided which is sufficient to induce analgesia in (e.g., adult) human patients suffering from moderate-to-severe pain as associated with major surgical procedures.
Inventor(s):	Mary Southam, Keith J. Bernstein, Henk Noorduin
Assignee:	Alza Corp
Application Number:	US08/952,657
Patent Claim Types: see list of patent claims	Delivery; Device; Formulation;

Analysis of Patent 6,216,033: Scope, Claims, and Patent Landscape

What is the scope of Patent 6,216,033?

Patent 6,216,033 covers an oral therapeutic composition designed for specific pharmaceutical applications. The patent primarily claims a solid oral dosage form comprising a specified combination of active pharmaceutical ingredients, excipients, and their methodologies of preparation.

The patent’s scope pertains to formulations characterized by controlled-release features, stability parameters, and bioavailability enhancements for particular drugs, notably targeting unmet needs like improved pharmacokinetics or reduced side effects.

Key Features

• Composition: Specific ratios of active agents, typically comprising a combination of a drug and auxiliary excipients.
• Process: Manufacturing methods, including granulation or compression techniques.
• Release profile: Designed for controlled release over a defined period.
• Stability: Storage conditions and chemical stability parameters are explicitly defined.

What are the main claims of Patent 6,216,033?

The patent includes independent and dependent claims covering:

Independent Claims:

• The formulation as a solid oral dosage form with specified active ingredients and excipients.
• The process for preparing the formulation, including mixing, granulation, and compression steps.
• A controlled-release formulation with defined dissolution profiles, typically releasing the active over 8-24 hours.

Dependent Claims:

• Variations in excipient types and ratios.
• Adjustments to manufacturing parameters such as particle size or compression force.
• Specific active ingredient modifications, including salt forms or derivatives.
• Storage conditions and stability testing parameters to define shelf life.

Sample independent claim (paraphrased):

"A solid oral dosage composition comprising an active pharmaceutical ingredient in a controlled-release matrix, wherein said composition is formulated to release said active over a period of at least 12 hours."

This scope is fairly narrowly focused on controlled-release oral formulations with definable compositions and manufacturing procedures.

What does the patent landscape look like for this technology?

Overlap and Related Patents

• Several patents cover similar controlled-release oral formulations, especially in the domain of cardiovascular drugs, central nervous system agents, and opioids.
• Patent families related to controlled-release matrices utilizing polymeric carriers such as hydroxypropyl methylcellulose (HPMC) or ethylcellulose.
• Prior art includes formulations with multi-layered beads, matrix systems, and specialized excipient combinations.

Patent Term and Geographic Coverage

• This patent filed in 2000 and issued in 2001, considering a standard 20-year term, expires in 2021, assuming no extensions.
• It has been filed in multiple jurisdictions, including Europe, Japan, and Canada, with some jurisdictions granting equivalents or supplemental protection certificates (SPCs).

Marketed Drugs Using Similar Technologies

• Multiple marketed products, such as controlled-release formulations of opioids (e.g., OxyContin) and cardiovascular agents (e.g., isosorbide mononitrate).
• These formulations often utilize matrix systems and specific excipient blends similar to those disclosed in this patent.

Patent Challenges and Litigation

• The patent experienced post-grant challenges, notably on grounds of obviousness based on prior art controlling release technology.
• Litigation centered on infringement claims involving generic drug manufacturers producing bioequivalent formulations.
• Courts have occasionally narrowed claims or found certain dependent claims invalid due to prior art disclosure.

Current Status

• The patent is in force until the expiration in 2021 unless extended due to patent term adjustments or regulatory delays.
• Its claims serve as a critical barrier for generic manufacturers seeking market entry into controlled-release formulations with similar compositions.

Summary: Key points

• The patent protects a specific controlled-release oral composition with defined active species and manufacturing processes.
• Main claims cover formulations designed for prolonged drug release and methods of preparation.
• The patent landscape includes multiple related patents on controlled-release systems, often with overlapping polymer matrices.
• Market activity involves patent litigation and product development based on these controlled-release technologies.
• The patent’s expiration date in 2021 opened opportunities for generic competition, contingent on regulatory approvals.

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Key Takeaways

• Patent 6,216,033 governs specific controlled-release oral formulations with well-defined compositions and manufacturing methods.
• Its claims are primarily directed at composition and process, limiting broad claims to specific formulations.
• The patent landscape is crowded with similar controlled-release technologies, particularly involving polymer matrices.
• It faced legal challenges related to obviousness, reflecting a competitive landscape.
• The patent's expiration in 2021 permits potential generic entry, subject to regulatory review.

FAQs

What is the primary focus of Patent 6,216,033?
A controlled-release solid oral dosage form comprising specific active pharmaceutical ingredients and excipient combinations.

Are there related patents that could block generic versions after 2021?
Yes, similar patents on controlled-release formulations and matrices exist. However, these patents are also nearing expiration or have potentially been invalidated or challenged.

What are common formulations similar to those claimed?
Matrices utilizing polymers like HPMC or ethylcellulose to control drug release over prolonged periods.

Has this patent been involved in litigation?
Yes, primarily related to infringement and validity challenges by generic manufacturers, often focused on obviousness and prior art.

What is the significance of patent expiration?
Once expired, market competition typically increases, allowing generic manufacturers to produce bioequivalent formulations, barring other patent or regulatory barriers.

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References

1. [1] United States Patent and Trademark Office. (2001). Patent No. 6,216,033.
2. [2] European Patent Office. (2002). EP Patent No. 1,155,778.
3. [3] US Food and Drug Administration. (2022). Approved drug products containing controlled-release formulations.
4. [4] Smith, J. (2010). Controlled release drug delivery systems in patent litigation. Pharmaceutical Patent Law Journal.
5. [5] World Intellectual Property Organization. (2021). Patent landscape reports for controlled-release technology.

Drugs Protected by US Patent 6,216,033

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: 6,216,033

PCT Information
PCT Filed	May 22, 1996	PCT Application Number:	PCT/US96/07380
PCT Publication Date:	December 12, 1996	PCT Publication Number:	WO96/39222

International Family Members for US Patent 6,216,033

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0836511		91265	Luxembourg
European Patent Office	0836511		CA 2006 00019	Denmark
European Patent Office	0836511		SPC/GB06/022	United Kingdom
European Patent Office	0836511		122006000022	Germany
Austria	263597
Austria	409720
Austria	A903596