United States Drug Patent 5,370,879: Claim Scope, Expiration, and 4-Aminopyridine Patent Landscape

US Patent 5,370,879 is a foundational controlled-release formulation patent covering sustained-release monoaminopyridine products, principally 4-aminopyridine, now known as fampridine or dalfampridine. Its claims cover multiparticulate pellets, polymeric membranes, dissolution profiles, immediate-release overlays, capsules, tablets, and 4-aminopyridine formulations. The patent has expired and does not currently block generic dalfampridine development in the United States.

The patent remains commercially relevant because later patents for Ampyra and dalfampridine adopted overlapping controlled-release concepts and generated substantial Paragraph IV litigation. US 5,370,879 itself is best treated as prior-art and historical foundation rather than an enforceable US patent right.

What does US Patent 5,370,879 cover?

US 5,370,879 covers pharmaceutical formulations that release a monoaminopyridine over approximately 12 to 24 hours and maintain therapeutically effective blood concentrations for treatment of neurological diseases involving impaired nerve impulse transmission.

The claim set has five principal technical components:

The active ingredient: a monoaminopyridine, with claim 27 specifically identifying 4-aminopyridine.
The dosage form: sustained-release pellets, capsules, tablets, or combinations of controlled-release and immediate-release pellets.
The release mechanism: polymer-coated cores or layered pellet structures.
The release profile: defined in vitro dissolution limits under USP XXII Type II testing at 50 rpm.
The therapeutic result: controlled absorption and maintenance of effective blood levels over 12 or 24 hours.

The claims are formulation claims, not claims to the basic pharmacological use of 4-aminopyridine. They require a particular sustained-release product configuration or release behavior.

What is the patent’s basic independent claim?

Claim 1 is the broadest formulation claim. It requires:

A sustained-release pharmaceutical formulation.
A therapeutically effective amount of a monoaminopyridine.
A carrier that permits controlled release.
Absorption over an average period of at least 12 hours.
Therapeutically effective blood levels for 12 to 24 hours.
Use in a neurological disease characterized by slowed nerve impulse transmission.

Claim 1 does not expressly require pellets, a particular polymer, a capsule, a tablet, or a specified dissolution curve. It is therefore broader in physical formulation terms than claims 2 through 27.

Its principal limitation is functional. The formulation must provide the stated controlled-absorption and therapeutic blood-level performance. A product that uses a different technology could potentially fall within the claim if it satisfies the claim's functional requirements, subject to claim construction and validity analysis.

How do claims 2 through 15 define the pellet technology?

Claims 2 through 15 narrow the invention to multiparticulate pellets with defined polymeric structures.

Claims	Principal limitation	Scope effect
2	Pellet core, multilayer membrane, water-insoluble polymer, optional water-soluble polymer, and 12-hour release profile	Establishes the central pellet architecture
3	24-hour dissolution profile	Narrows claim 2 to an extended 24-hour release pattern
4	12-hour dissolution profile	Narrows claim 2 to a 12-hour release pattern
5	Layered core made from powder and polymeric material	Requires a specific layered manufacturing structure
6	Enumerated water-soluble polymers	Limits the hydrophilic polymer selection
7	Freely permeable acrylic or methacrylic copolymer	Alternative to the water-soluble polymer
8	Enumerated water-insoluble synthetic polymers	Limits the hydrophobic polymer selection
9	Shellac, chitosan, or gum juniper	Limits the natural-polymer selection
10	Slightly permeable acrylic or methacrylic copolymer	Alternative to the water-insoluble polymer
11	Build-up on an inert core	Requires a nonactive central substrate
12	Sugar/starch non-pareil seed, 0.2 to 1.4 mm	Specifies seed composition and size
13	Central active core	Requires the active ingredient in the core
14	Homogeneous active-polymer blend formed into a core and layered	Specifies a central-core manufacturing method
15	Completed core diameter of 0.4 to 1.6 mm	Adds a particle-size limitation

Claim 2 is the most commercially significant pellet claim. It requires a core containing monoaminopyridine and excipients, surrounded by a multilayer membrane containing a major proportion of water-insoluble film-forming polymer. The claim also requires a dissolution profile under USP XXII Type II conditions:

No more than 50% released after one hour.
No more than 75% released after four hours.
Complete release no earlier than eight hours.

Claims 3 and 4 create separate 24-hour and 12-hour dissolution-profile alternatives. Their ranges are relatively broad, which historically increased the potential coverage of different coating thicknesses, polymer ratios, and pellet populations.

Why are the polymer lists important?

Claims 6 through 10 provide material-specific fallback positions. They identify hydrophilic polymers such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, methyl cellulose, polyethylene glycol, agar, carrageenan, and xanthan.

The hydrophobic list includes ethylcellulose, cellulose derivatives, acrylic and methacrylic polymers, polyolefins, polyvinyl acetate, polyvinyl chloride, and polyurethane. Claims 9 and 10 extend the alternatives to natural polymers and slightly permeable acrylic or methacrylic copolymers.

These claims would have been useful against a formulation that avoided one named polymer but used another polymer falling within the enumerated alternatives. They also create prosecution-history and claim-differentiation issues because the patent expressly distinguishes water-soluble, water-insoluble, freely permeable, and slightly permeable polymeric materials.

What release profiles are protected?

Claims 3, 4, and 17 through 19 use dissolution testing as a central boundary for infringement.

Twelve-hour pellet profiles

Claim 4 requires:

Time point	Release range
1 hour	0% to 40%
4 hours	20% to 60%
8 hours	30% to 80%
12 hours	At least 75%

Twenty-four-hour pellet profile

Claim 3 requires:

Time point	Release range
1 hour	0% to 40%
4 hours	20% to 60%
8 hours	30% to 80%
12 hours	50% to 90%
24 hours	At least 75%

Immediate-release plus sustained-release profiles

Claims 16 through 23 cover formulations combining controlled-release pellets with a rapid-release quantity of monoaminopyridine. Claim 20 permits up to 60% by weight of rapid-release monoaminopyridine. Claims 21 through 23 address rapid-release pellets and impose additional dissolution requirements.

This combination is designed to produce an initial therapeutic exposure followed by prolonged blood levels. In patent terms, the claims cover both the sustained-release component and the pharmacokinetic rationale for adding an immediate-release fraction.

How broad is claim 27 for 4-aminopyridine?

Claim 27 depends on claim 2 and limits the monoaminopyridine to 4-aminopyridine. It therefore does not cover every 4-aminopyridine product. An accused product would also need to satisfy claim 2's pellet, membrane, polymer, and dissolution limitations.

The dependency is significant:

Claim 1 potentially reaches a broader class of monoaminopyridines and carriers.
Claim 2 requires the specific multilayer pellet structure.
Claim 27 narrows claim 2 to 4-aminopyridine.

Claim 27 does not independently claim an immediate-release 4-aminopyridine product, a method of treating multiple sclerosis, or a particular tablet strength.

When did US Patent 5,370,879 expire?

US 5,370,879 issued on December 6, 1994. Because it is a pre-June 8, 1995 US application, its term was generally governed by the earlier of 17 years from grant or 20 years from the effective US nonprovisional filing date, subject to applicable adjustments and extensions. The patent's ordinary 17-year term from issuance ended in December 2011.[1]

Event	Date
US patent issued	December 6, 1994
Ordinary 17-year expiration	December 6, 2011
Current enforceability	Expired
Current US blocking right	None

The patent is therefore not an active exclusionary right against a generic or follow-on dalfampridine product. Any current US freedom-to-operate analysis must focus on later patents, regulatory exclusivity, trade secrets, manufacturing know-how, and product-specific Orange Book listings.

What is the Orange Book status of US 5,370,879?

US 5,370,879 is expired and is not a current Orange Book barrier for Ampyra or dalfampridine. The FDA Orange Book analysis for a generic applicant turns on patents listed against the relevant reference-listed drug, not on every historical patent that may have covered an earlier formulation concept.[2]

Ampyra, marketed by Acorda Therapeutics, was approved as dalfampridine extended-release tablets in a 10 mg strength. Its later patent estate, rather than US 5,370,879, drove the Paragraph IV disputes involving generic applicants.[3]

An expired formulation patent can still matter as:

Prior art against later patent applications.
Evidence of the state of the art.
A source of disclosure for formulation design.
A reference in validity or obviousness litigation.
A possible basis for assessing whether later claims are patentably distinct.

It cannot support a new US infringement action after expiration.

What later patents covered Ampyra and dalfampridine?

The later US patent estate included formulation and method-of-use patents associated with extended-release 4-aminopyridine products.

Patent	General subject matter	Landscape significance
US 5,540,938	Sustained-release 4-aminopyridine formulation	Core later formulation patent associated with Ampyra
US 5,800,428	Sustained-release 4-aminopyridine technology	Related formulation protection
US 6,176,880	Controlled-release 4-aminopyridine formulation technology	Later formulation-layer protection
US 8,007,826	Treatment of multiple sclerosis with 4-aminopyridine	Method-of-use protection
US 8,663,685	Dalfampridine extended-release tablet technology	Later product and formulation protection

The exact enforceability of each patent depended on claim scope, expiration adjustments, terminal disclaimers, patent-term extension, prosecution history, and litigation outcomes. The central commercial dispute concerned whether later patents validly distinguished Ampyra from earlier controlled-release 4-aminopyridine disclosures, including the technology represented by US 5,370,879.

Which companies challenged Ampyra patents?

Generic applicants including Roxane Laboratories, Mylan Pharmaceuticals, Teva Pharmaceuticals, and Sandoz filed abbreviated new drug applications and Paragraph IV certifications against Ampyra-related patents. The principal litigation involved Acorda Therapeutics and its patent holders against generic manufacturers.

In Acorda Therapeutics Inc. v. Roxane Laboratories, Inc., the Federal Circuit addressed the validity of patents covering sustained-release 4-aminopyridine and treatment of multiple sclerosis. The court affirmed findings that the asserted claims were obvious, removing major patent barriers to generic entry.[4]

The litigation had several practical consequences:

Generic applicants could challenge the later Ampyra estate without infringing US 5,370,879, which had already expired.
The validity of later formulation claims became the key issue.
The court considered whether a skilled artisan would have been motivated to combine known 4-aminopyridine therapy with sustained-release technology.
The commercial value of the estate shifted from broad historical formulation concepts to narrower product, dosing, and use claims.

Were there Paragraph IV settlements?

Paragraph IV challenges to Ampyra-related patents led to patent litigation and settlement activity. Publicly reported settlement terms in pharmaceutical cases do not always disclose the complete commercial arrangement, launch date, authorized-generic provisions, or manufacturing restrictions.

The key legal point is that a settlement concerning later Ampyra patents would not revive, extend, or otherwise enforce US 5,370,879. A settlement can delay generic entry under later patents, but it cannot create a new term for an expired patent.

For diligence purposes, settlements should be separated into:

Patent litigation agreements.
Authorized-generic arrangements.
Supply or licensing agreements.
Product-development collaborations.
Commercial launch commitments.

They have different effects on entry timing and revenue exposure.

What was the FDA regulatory status of dalfampridine?

FDA approved Ampyra, a 10 mg extended-release dalfampridine tablet, on January 22, 2010, for improving walking in adults with multiple sclerosis, as demonstrated by an increase in walking speed.[3]

Dalfampridine is the United States adopted name for 4-aminopyridine. Outside the United States, fampridine extended-release products have been marketed under names including Fampyra.

Regulatory item	Status
Active ingredient	Dalfampridine, also called fampridine or 4-aminopyridine
Reference product	Ampyra extended-release tablets
Strength	10 mg
FDA approval	January 22, 2010
Dosage form	Extended-release oral tablet
Main approved use	Improvement of walking in adults with multiple sclerosis
Primary generic pathway	ANDA with Paragraph IV or other applicable certifications

The product's regulatory profile is important because generic dalfampridine applicants must demonstrate pharmaceutical equivalence, bioequivalence, and compliance with extended-release product requirements. A formulation that avoids an expired patent may still face development challenges involving dose dumping, alcohol effects, food effects, content uniformity, dissolution, and manufacturing reproducibility.

What formulation patents remain relevant after US 5,370,879 expired?

The expired patent's technical disclosures remain relevant to several modern design-around questions.

Polymer coating design

A developer can evaluate:

Single-layer versus multilayer coatings.
Hydrophilic and hydrophobic polymer ratios.
Membrane porosity.
Film thickness.
Coating weight gain.
Acrylic versus cellulose-based polymers.
Osmotic, matrix, or ion-exchange technologies.

A product using a non-pellet matrix tablet may avoid claims requiring the multilayer pellet structure, but it must be assessed against later patents and any broader functional claims.

Release-profile design

The patent uses multiple dissolution windows. A product that falls outside those windows may avoid a literal limitation, but dissolution testing must use comparable apparatus, media, agitation, sampling, and analytical methods. Small changes in coating thickness or polymer ratio can alter whether a product falls inside a claimed range.

Immediate-release fraction

Claims 16 through 23 create potential coverage for products that combine rapid-release and sustained-release fractions. A developer using a uniform extended-release matrix without an immediate-release fraction would not necessarily meet these limitations, although other patents may apply.

Pellet size and seed selection

Claims 11 through 15 focus on inert seeds, active cores, layered structures, and specified diameters. A formulation using a substantially different particle architecture may avoid these dependent claims, but the commercial relevance of those claims is limited by expiration.

How strong was the patent estate?

US 5,370,879 had historically meaningful scope but limited present-day strength because it is expired. Its historical strengths were:

Broad coverage of sustained-release monoaminopyridine formulations.
Functional coverage of 12- and 24-hour controlled absorption.
Multiple polymer alternatives.
Detailed dissolution-profile claims.
Coverage of both capsules and tablets.
Immediate-release and sustained-release combinations.
Specific 4-aminopyridine coverage through claim 27.

Its weaknesses included:

Dependence on broad functional performance language.
Extensive use of known pharmaceutical polymers.
Potential obviousness issues based on conventional sustained-release technology.
Narrower dependent claims that required specific materials, sizes, and dissolution behavior.
A patent term that ended before Ampyra became commercially significant.

Later patents carried greater commercial value because they were closer to the approved product and its therapeutic indication. Those patents also faced obviousness challenges based on the earlier 4-aminopyridine and sustained-release literature.

What generic launch risks exist today?

US 5,370,879 creates no current generic launch risk because it expired in 2011. The relevant risk profile for a dalfampridine extended-release product is now concentrated in four areas:

Later unexpired patents, if any remain listed for the reference product.
FDA requirements for bioequivalence and dissolution matching.
Manufacturing reproducibility for a narrow therapeutic-index product.
Commercial competition from existing generic dalfampridine suppliers.

The most important development risk is regulatory rather than infringement risk. Dalfampridine has a narrow dosing margin, and the FDA label warns against exceeding the recommended dose because seizure risk increases with higher exposure.[3]

How does US 5,370,879 compare with later Ampyra patents?

Issue	US 5,370,879	Later Ampyra patents
Primary focus	Broad sustained-release monoaminopyridine formulation	Product-specific formulation and MS treatment
Active ingredient	Monoaminopyridine; claim 27 specifies 4-aminopyridine	Primarily dalfampridine or 4-aminopyridine
Dosage forms	Pellets, capsules, tablets	Extended-release tablets and treatment regimens
Release period	12 to 24 hours	Product-specific release and dosing requirements
Use claim	Neurological disease broadly	Multiple sclerosis walking impairment
Current status	Expired	Dependent on individual patent terms and litigation
Commercial role	Foundational prior art	Direct Ampyra market protection

Key Takeaways

US 5,370,879 covers sustained-release monoaminopyridine formulations, especially pellet-based 4-aminopyridine products.
Claim 1 is broadly functional; claim 2 establishes the central multilayer pellet architecture.
Claims 3 and 4 define 24-hour and 12-hour dissolution profiles.
Claims 16 through 23 cover combinations of sustained-release and rapid-release monoaminopyridine.
Claim 27 specifically limits claim 2 to 4-aminopyridine.
The patent expired on December 6, 2011, based on its ordinary 17-year term from issuance.
It is not a current Orange Book barrier to generic dalfampridine.
Later Ampyra-related patents, including US 5,540,938 and US 8,007,826, were more important to commercial exclusivity.
Acorda's litigation against generic companies resulted in major validity rulings against later asserted patents.
Current generic risk is primarily tied to later patent status, FDA bioequivalence, dissolution performance, manufacturing controls, and commercial scale.

FAQs

Does US 5,370,879 claim Ampyra by name?

No. The patent predates the Ampyra product name. Claim 27 identifies 4-aminopyridine, the active ingredient later marketed in the United States as dalfampridine.

Does the patent cover a standard immediate-release 4-aminopyridine tablet?

No. The claims require sustained-release or controlled-absorption characteristics. Claims 16 through 23 require an immediate-release component in combination with sustained-release pellets.

Can a generic manufacturer rely on US 5,370,879 as a freedom-to-operate defense?

The patent's expiration eliminates infringement liability under this patent. Its disclosure may still be relevant to validity and prior-art analyses for later patents.

Does a matrix tablet automatically avoid the pellet claims?

A matrix tablet may avoid claims requiring pellets, pellet cores, or multilayer pellet membranes. It must still be reviewed against claim 1 and later formulation patents, which may use different structural limitations.

Is fampridine the same active ingredient as dalfampridine?

Yes. Fampridine and dalfampridine refer to 4-aminopyridine. Dalfampridine is the United States established name used for the extended-release multiple-sclerosis product.

References

United States Patent and Trademark Office. (1994). US Patent No. 5,370,879, sustained release formulations of monoaminopyridines. Google Patents. https://patents.google.com/patent/US5370879A/en
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (2023). Ampyra (dalfampridine) extended-release tablets prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc., 903 F.3d 1310 (Fed. Cir. 2018).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Ireland	3952/90	Feb 11, 1990

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0484186	⤷ Start Trial	C300503	Netherlands	⤷ Start Trial
European Patent Office	0484186	⤷ Start Trial	91894	Luxembourg	⤷ Start Trial
European Patent Office	0484186	⤷ Start Trial	CA 2011 00031	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,370,879

Summary for Patent: 5,370,879