Details for Patent: 7,727,548

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Summary for Patent: 7,727,548

Title:	Rapidly disintegrable tablet containing polyvinyl alcohol
Abstract:	The present invention provides a quickly disintegrating tablet which has quick disintegrability and solubility in an oral cavity, and does not have uncomfortable tastes such as bitterness, has a small variation of a tablet physical property even in storage under a humidifying condition, and has substantially no change in a medicine content in the tablet and tablet appearance and which is superior in stability; and a manufacturing method of the tablet. That is, it provides: a quickly disintegrating tablet which is prepared by blending a medicine with a saccharide and polyvinyl alcohol, which has small variations of tablet weight, tablet hardness, tablet diameter and tablet thickness, and which is superior in medicine stability in the tablet; and a manufacturing method of the tablet.
Inventor(s):	Yutaka Morita, Masanobu Yasui, Takayuki Ohwaki, Yuki Tsushima
Assignee:	Eisai R&D Management Co Ltd
Application Number:	US10/203,687
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,727,548
Patent Claim Types: see list of patent claims	Use; Dosage form;

US Patent 7,727,548: Claim Scope, Expiration, Orange Book Relevance, and Donepezil Patent Landscape

US Patent 7,727,548 protects a narrow compressed, orally disintegrating tablet formulation that combines mannitol and polyvinyl alcohol, or PVA, at specified weight ratios. Its strongest commercial relevance is to donepezil hydrochloride orally disintegrating tablets, although claim 1 also covers formulations containing famotidine, midodrine hydrochloride, or brotizolam.

The patent does not broadly protect donepezil, donepezil hydrochloride, or every orally disintegrating donepezil tablet. Infringement requires the accused product to satisfy the drug-identity, compressed-tablet, rapid-oral-disintegration, mannitol, and PVA limitations. The patent's practical value therefore depends on the exact excipient composition and on whether the patent term and any relevant Orange Book listing remain active.

What does US Patent 7,727,548 protect?

The patent protects a quickly disintegrating compressed tablet containing:

• One of four specified medicines:
  • Famotidine
  • Midodrine hydrochloride
  • Brotizolam
  • Donepezil hydrochloride
• Mannitol at not less than 0.8 part by weight per one part by weight of the tablet
• PVA at 0.0001 to 0.1 part by weight per one part by weight of the tablet
• A compressed tablet structure
• Disintegration in the oral cavity

Claim 2 narrows claim 1 to donepezil hydrochloride. Claim 3 covers oral administration of a tablet meeting claim 1.

Claim	Subject matter	Scope
1	Quickly disintegrating compressed tablet with one of four medicines, mannitol, and PVA in specified amounts	Broadest composition claim
2	Claim 1 where the medicine is donepezil hydrochloride	Narrow donepezil formulation claim
3	Method of orally administering a tablet of claim 1	Method-of-use claim

The use of “comprising” makes claim 1 open-ended. An accused formulation can contain additional active ingredients or excipients and still fall within the claim if it includes every required limitation.

How should the mannitol and PVA limitations be calculated?

The claim expresses both excipients as parts by weight relative to the total tablet weight.

A mannitol ratio of 0.8 part by weight or more means at least approximately 80% of the tablet by weight, assuming the claim's denominator is the total tablet weight. PVA must be present at between approximately 0.01% and 10% by weight.

Component	Claimed ratio	Approximate percentage of tablet weight
Mannitol	0.8 or more	At least 80%
PVA	0.0001 to 0.1	0.01% to 10%

The ratios create a significant technical constraint. A product with 79% mannitol would generally fall outside the literal scope of the mannitol limitation, subject to claim construction and the doctrine of equivalents. A product with no PVA also falls outside the literal claim.

The wording creates a potential interpretation issue because “a compounding ratio ... to one part by weight of the tablet” is unusual drafting. The most commercially relevant reading treats the tablet as the denominator. A court would examine the specification, prosecution history, examples, and technical usage to confirm the calculation method.

What formulations are protected by US 7,727,548?

Donepezil orally disintegrating tablets

Claim 2 is the commercially important formulation claim. It covers a donepezil hydrochloride tablet that also satisfies the mannitol, PVA, compression, and oral-disintegration requirements.

The claim does not require a particular donepezil strength, such as 5 mg or 10 mg, unless a limitation appears elsewhere in the patent claims or specification. It also does not expressly require a flavoring agent, lubricant, sweetener, granulation process, tablet hardness, or a specific disintegration time.

The absence of those limitations gives claim 2 broader coverage than a claim tied to a particular dosage strength or manufacturing sequence. The mannitol and PVA thresholds remain essential.

Famotidine, midodrine hydrochloride, and brotizolam

Claim 1 also covers quickly disintegrating tablets containing the three non-donepezil medicines. These alternatives expand the formal claim scope but may have lower current commercial value than the donepezil embodiment.

Claim 2 cannot be infringed by a famotidine, midodrine, or brotizolam product because it requires donepezil hydrochloride.

Other active ingredients

A tablet containing an active ingredient not named in claim 1 does not literally satisfy the “medicine is” limitation. The open-ended “comprising” language permits additional ingredients, but it does not ordinarily eliminate the requirement that the named medicine be present.

How strong is the patent estate for donepezil?

US 7,727,548 is a formulation patent, not the basic compound patent for donepezil. Its value must be separated from the earlier patent estate covering donepezil itself.

Patent category	Protection target	Competitive relevance
Compound patents	Donepezil and related piperidine compounds	Controlled the original active ingredient
Salt or polymorph patents	Donepezil hydrochloride forms or solid-state properties	May affect API manufacture
Formulation patents	Orally disintegrating tablets, excipients, release characteristics	Relevant to Aricept ODT and similar products
Method-of-use patents	Treatment of cognitive disorders or related conditions	Scope depends on the claimed indication
Manufacturing patents	Synthesis, purification, granulation, compression, or coating	Can create process barriers without blocking the finished product

US 7,727,548 has a narrower blocking position than a compound patent because a competitor can potentially design around the formulation limitations. The main design-around routes include:

1. Replacing PVA with another binder or film-forming polymer.
2. Reducing mannitol below the claimed threshold.
3. Using a noncompressed dosage form.
4. Developing a tablet that disintegrates rapidly but uses a different excipient system.
5. Using a different active ingredient, where clinically and commercially appropriate.
6. Demonstrating that the product does not disintegrate in the oral cavity as required by the claim.

A formulation that uses mannitol at 80% or more and PVA within the claimed range presents the highest literal infringement risk.

Does the patent cover every orally disintegrating donepezil product?

No. The patent's scope is narrower than the product category “donepezil orally disintegrating tablet.”

A competing product may avoid literal infringement if it:

• Uses another disintegrant or binder instead of PVA;
• Uses a PVA amount outside the claimed range;
• Uses less than 0.8 part mannitol per part of tablet;
• Is not compressed;
• Does not satisfy the oral-cavity disintegration limitation; or
• Contains a different active ingredient.

The word “quickly” is potentially functional, but the claim also states that the tablet “quickly disintegrates in an oral cavity.” The specification and prosecution history would likely be important in defining the required disintegration performance. Testing should use the patent's examples and any prosecution-defined parameters where available.

What is the scope of method claim 3?

Claim 3 covers orally administering a medicine in the form of the tablet of claim 1 to a patient in need thereof.

The method claim incorporates all limitations of claim 1. It therefore requires:

• One of the four specified medicines;
• Mannitol at the claimed level;
• PVA within the claimed range;
• A compressed tablet;
• Oral-cavity disintegration; and
• Administration to a patient in need.

The claim is not a broad method of treating Alzheimer's disease with donepezil. It is a method of administering the specifically claimed tablet. A finished dosage product can potentially raise both composition and method-claim issues when used according to the claimed administration.

For generic-drug litigation, the method claim's practical importance depends on the proposed labeling. A generic applicant may challenge the claim through a Paragraph IV certification or may attempt a section viii statement that omits a protected indication or method. A section viii carve-out is less useful where the claim is directed to the composition and ordinary use of the dosage form rather than a separable indication.

When does US Patent 7,727,548 lose exclusivity?

The patent issued on May 25, 2010. The ordinary US patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory effects (35 U.S.C. § 154).

The relevant commercial conclusion is that the patent's ordinary term would have ended approximately two decades after its earliest effective US or international filing date, likely in the early 2020s. The exact enforceable expiration date must be taken from the USPTO patent record after accounting for patent-term adjustment and any terminal disclaimer.

Event	Date or status
Patent number	US 7,727,548
Grant date	May 25, 2010
Patent type	Formulation and administration claims
Ordinary term framework	20 years from the applicable earliest filing date
Patent-term extension	No extension is established from the supplied claim information
Current relevance	Depends on the official USPTO expiration and maintenance records

Patent expiration and FDA exclusivity are separate concepts. Expiration of the patent does not itself establish whether a product has regulatory exclusivity, and FDA exclusivity does not extend the patent term.

What is the Orange Book status of US 7,727,548?

The Orange Book lists patents submitted by an NDA holder for an approved drug product when the patents meet FDA listing requirements. A formulation patent may be listed if it claims the approved drug product, an approved formulation, or an approved method of use. The patent number alone does not establish Orange Book listing.

For donepezil, the relevant product category includes:

• Aricept tablets;
• Aricept orally disintegrating tablets; and
• Generic donepezil hydrochloride products approved through abbreviated new drug applications.

The key regulatory questions are whether US 7,727,548 was listed against an NDA covering donepezil orally disintegrating tablets, whether the listing was removed or expired, and whether an ANDA applicant had to address it with a Paragraph IV certification.

The FDA Orange Book should be read together with the patent's USPTO record. An Orange Book entry can affect ANDA certification and litigation timing, but it does not expand the patent's claim scope. Conversely, an unlisted patent can still be enforceable against an infringing product, although it may not create the same ANDA litigation mechanism as a listed patent (FDA, 2024; 21 C.F.R. § 314.53).

Which companies are most exposed to this patent?

The highest exposure would have existed for companies marketing or developing a donepezil orally disintegrating tablet with a composition matching the claimed excipient profile.

Company or product category	Potential exposure
Eisai and affiliated Aricept products	Originator-side ownership or licensing relevance
Generic ANDA applicants for donepezil ODT	Highest Paragraph IV and formulation-design risk
Contract manufacturers	Manufacturing exposure if they produce an infringing formulation
API suppliers	Generally lower exposure unless they participate in formulation or induced infringement
Developers of non-ODT donepezil tablets	Low exposure because the oral-disintegration limitation is central
Developers of liquid or orally dissolving films	Potentially lower exposure because the claim requires a compressed tablet

The patent does not create biosimilar risk. Donepezil hydrochloride is a small-molecule active ingredient, and competing products proceed through the generic-drug framework rather than the biosimilar pathway under the Public Health Service Act.

What Paragraph IV challenges and litigation affect the patent?

A Paragraph IV challenge would be relevant if the patent was listed in the Orange Book for the reference product and an ANDA applicant certified that the patent was invalid, unenforceable, or not infringed.

The likely technical issues in such litigation would include:

• Whether the proposed product contains at least 0.8 part mannitol per part of tablet;
• Whether PVA falls within the 0.0001-to-0.1 range;
• Whether the product is compressed;
• Whether it quickly disintegrates in the oral cavity;
• Whether the active ingredient is donepezil hydrochloride or another named medicine;
• Whether the claims are anticipated or obvious over earlier orally disintegrating tablet technology;
• Whether the patent adequately describes and enables the full claimed range; and
• Whether prosecution history limits the interpretation of “quickly disintegrates.”

No specific litigation, settlement agreement, or license can be attributed to US 7,727,548 solely from the claims supplied. A litigation search must distinguish cases naming the patent from cases involving other donepezil patents.

How does US 7,727,548 compare with compound and method-of-use patents?

Issue	US 7,727,548	Donepezil compound patent	Broad method-of-use patent
Protected subject	Tablet formulation	Active pharmaceutical ingredient	Treatment method
Product dependence	High	Moderate	Variable
Design-around potential	Relatively high	Low before expiry	Depends on indication
Relevance to ODT products	Direct	Indirect after compound expiry	Usually indirect
Key infringement proof	Composition and disintegration testing	Chemical identity and product content	Labeling and administration
Biosimilar relevance	None	None	None

The patent's strongest claim is likely claim 2 because it targets donepezil ODT products specifically. Its weakness is the number of objective formulation variables available to a competitor.

What generic launch scenarios exist?

Scenario 1: Formulation outside the PVA range

A generic company could use no PVA or a different amount. This is the cleanest design-around if tablet performance remains acceptable.

Scenario 2: Mannitol below the threshold

Reducing mannitol below the claimed level may avoid literal infringement. The developer would need to preserve acceptable taste, hardness, manufacturability, and disintegration.

Scenario 3: Noncompressed dosage form

An oral film, granule, suspension, or other dosage form could avoid the compressed-tablet limitation. Regulatory comparability and product stability would determine commercial feasibility.

Scenario 4: Paragraph IV challenge

An ANDA applicant could assert that the claims are invalid or not infringed. The most credible validity arguments would likely focus on obviousness and the predictability of combining high mannitol content with a small amount of PVA in an orally disintegrating tablet.

Scenario 5: Post-expiration entry

Once the patent term ends, the formulation claims no longer block commercial manufacture, subject to any separate unexpired patents, regulatory exclusivities, trademarks, and supply constraints.

Key Takeaways

• US 7,727,548 is a formulation patent covering a compressed, orally disintegrating tablet.
• Claim 1 requires famotidine, midodrine hydrochloride, brotizolam, or donepezil hydrochloride.
• Claim 2 is the principal donepezil claim.
• Mannitol must be at least approximately 80% of tablet weight under the ordinary reading of the claim.
• PVA must be present at approximately 0.01% to 10% by weight.
• The patent does not cover every donepezil ODT, every donepezil product, or the donepezil molecule itself.
• A PVA-free formulation, a formulation with less than 80% mannitol, or a noncompressed dosage form may provide a design-around.
• Claim 3 is a narrow administration claim that incorporates the full composition limitations of claim 1.
• The patent has no biosimilar relevance.
• The enforceable expiration date and Orange Book status must be determined from the USPTO and FDA records, respectively.
• Any Paragraph IV risk depends on the proposed product's exact excipient composition and the patent's listing status.

FAQs

Does US 7,727,548 cover donepezil tablets with crospovidone instead of PVA?

Not literally, unless the formulation also contains PVA within the claimed range. Crospovidone does not satisfy the express PVA limitation.

Can a donepezil orally disintegrating tablet avoid the patent by using 79% mannitol?

Potentially. A formulation with less than 0.8 part mannitol per part of tablet would not literally meet the mannitol limitation, although an equivalence theory could still be asserted.

Does the patent cover donepezil oral films?

Claim 1 requires a compressed tablet. A film ordinarily would not satisfy that limitation, although the precise dosage-form structure would control.

Is US 7,727,548 a patent on Aricept itself?

No. It is directed to a particular quickly disintegrating tablet formulation. Aricept and donepezil have separate compound, product, formulation, trademark, and regulatory rights.

Can a generic company launch a conventional donepezil tablet after this patent expires?

The patent claims supplied here focus on quickly disintegrating compressed tablets. A conventional immediate-release tablet may fall outside the claims, but launch also requires review of any other unexpired patents, FDA exclusivity, ANDA status, and applicable regulatory requirements.

References

1. United States Patent and Trademark Office. (2010). US Patent No. 7,727,548, Quickly disintegrating tablet.

2. United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

4. Electronic Code of Federal Regulations. (2024). 21 C.F.R. § 314.53, Submission of patent information.

Drugs Protected by US Patent 7,727,548

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: 7,727,548

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2000-56176	Mar 01, 2000

PCT Information
PCT Filed	March 01, 2001	PCT Application Number:	PCT/JP01/01575
PCT Publication Date:	September 07, 2001	PCT Publication Number:	WO01/64190

International Family Members for US Patent 7,727,548

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	437632
Germany	60139379
Denmark	1260215
European Patent Office	1260215
Spain	2327898
Japan	4107842
Portugal	1260215