United States Patent 4,371,516: Claim Scope, Expiration, and Fast-Dissolving Dosage-Form Patent Landscape

United States Patent 4,371,516 is a foundational patent for freeze-dried, fast-disintegrating oral dosage forms associated with the Zydis technology platform. Its claims require an open matrix dosage form, a water-soluble or water-dispersible carrier, and disintegration in water within 10 seconds. The process claims require sublimation of solvent from a molded, solidified composition.

The patent issued on February 1, 1983, and its ordinary 17-year United States patent term expired on February 1, 2000, subject to any applicable term adjustment or term extension. No current United States exclusivity remains under this patent. The patent is relevant historically and technically, but it should not by itself block a generic or orally disintegrating dosage-form product today.

What does United States Patent 4,371,516 cover?

The patent covers three related subject matter categories:

A fast-disintegrating solid oral dosage form.
A manufacturing process using solvent sublimation from a molded composition.
Oral administration of the resulting dosage form.

The core technical concept is a porous, open matrix that carries a pharmaceutical substance. The matrix is produced by freezing or otherwise placing a solvent-containing composition into a solid state and then removing solvent by sublimation. The resulting structure permits rapid penetration of water and rapid disintegration.

Patent identification and status

Item	Data
Patent	U.S. Patent No. 4,371,516
Title	Pharmaceutical compositions
Issued	February 1, 1983
Technology	Freeze-dried, rapidly disintegrating oral dosage forms
Principal commercial association	R.P. Scherer Corporation and the Zydis platform
Ordinary pre-1995 U.S. patent term	17 years from grant
Ordinary expiration date	February 1, 2000
Current status	Expired
Orange Book status	Not an Orange Book drug patent as such
Biosimilar relevance	None; the patent covers a dosage-form technology, not a biologic

The patent should be analyzed separately from later patents covering particular active ingredients, formulations, packaging systems, manufacturing controls, or commercial products.

What are the limitations of claim 1?

Claim 1 is the principal product claim. It requires each of the following elements:

Claim element	Scope
Dosage form	Pharmaceutical dosage form for oral administration
Physical state	Solid
Performance	Disintegrates in water within 10 seconds
Structural form	Open matrix network
Contents	Carries a unit dosage of a pharmaceutical substance
Matrix material	Pharmacologically acceptable, water-soluble or water-dispersible carrier
Specified carriers	Partially hydrolysed gelatin, hydrolysed dextran, or alginate
Carrier combinations	One of those materials mixed with polyvinyl alcohol, polyvinylpyrrolidone, or acacia
Composition language	"Consists essentially of" the specified matrix system

Open matrix requirement

"Open matrix network" is a structural limitation, not merely a statement that the dosage form dissolves quickly. The claim requires a porous or interconnected matrix capable of allowing water to penetrate the dosage form. A conventional compressed tablet that disintegrates in less than 10 seconds would not necessarily satisfy this limitation.

The open matrix limitation distinguishes the claimed dosage form from conventional tablets made by compression, wet granulation, or direct compression. A later product could have rapid oral disintegration but avoid the claim if it lacks the claimed matrix structure or uses a materially different architecture.

Ten-second disintegration requirement

The claim requires disintegration by water within ten seconds. The patent does not merely claim a dosage form that dissolves rapidly in the mouth. Product testing would need to address:

The test medium.
Water temperature.
Agitation conditions.
Sample size.
Whether the test measures complete disintegration or dissolution.
The number of tested units.
The analytical endpoint.

Disintegration and dissolution are different concepts. A dosage form can disintegrate rapidly while the active ingredient dissolves more slowly. Conversely, a rapidly dissolving formulation may not have the claimed open matrix.

Carrier limitation

The carrier must fall within the recited group:

Partially hydrolysed gelatin.
Hydrolysed dextran.
Alginate.
A mixture of one of those carriers with polyvinyl alcohol.
A mixture with polyvinylpyrrolidone.
A mixture with acacia.

The claim is narrower than a generic claim to any lyophilized oral dosage form. A formulation using mannitol, maltodextrin, pullulan, starch, or another excipient would require separate analysis. It may avoid literal infringement if the claimed carrier is absent, although the "consists essentially of" language may raise an equivalent-composition issue in some circumstances.

"Consists essentially of" limitation

"Consists essentially of" permits additional components that do not materially affect the basic and novel characteristics of the claimed invention. The relevant basic characteristics are likely the open matrix structure, rapid water disintegration, and specified carrier system.

The language is narrower than "comprising" but broader than "consisting of." Additional ingredients such as active pharmaceutical ingredients, flavoring agents, colors, preservatives, buffers, sweeteners, and certain processing aids may be compatible with the claim. The question is whether an added component materially changes the matrix or its rapid-disintegration performance.

What do claims 2 through 4 protect?

Claims 2 through 4 cover the manufacturing process.

Claim 2: sublimation process

Claim 2 requires:

A pharmaceutical substance.
A solution of the specified carrier material in a solvent.
A composition placed in a mold corresponding in size and shape to the dosage form.
The composition in a solid state in the mold.
Removal of solvent by sublimation.
Formation of an open matrix carrying the pharmaceutical substance.
Disintegration of the matrix by water within ten seconds.

The process is directed to a molded, solidified composition followed by solvent sublimation. In practical terms, this describes a freeze-drying or lyophilization process in which frozen solvent is removed directly as vapor.

A process that dries a liquid by evaporation, spray-dries a composition, or compresses dry powders may avoid literal infringement of claim 2 even if it produces a rapidly disintegrating product. The analysis turns on whether the accused process includes sublimation from the solid state in the mold.

Claim 3: coloring, flavoring, or preservative

Claim 3 adds a coloring agent, flavoring agent, or preservative to the claim 2 process. It has limited independent commercial significance because these additives are common in oral dosage forms. Its value was primarily dependent on the validity and scope of claim 2.

Claim 4: water as solvent

Claim 4 narrows claim 2 by specifying water as the solvent. This is commercially important because aqueous carrier solutions are common in pharmaceutical lyophilization. It is also technically narrow because it excludes processes using only nonaqueous solvents.

What does claim 5 cover?

Claim 5 is a method-of-use claim for orally administering the dosage form to a mammal. It requires insertion into the mammal's mouth of a solid dosage form that:

Disintegrates in water within ten seconds.
Has an open matrix network.
Uses the specified water-soluble or water-dispersible carrier materials.

As supplied, claim 5 does not expressly repeat the "unit dosage of a pharmaceutical substance" limitation found in claim 1. That drafting difference may affect claim construction. The claim still requires a pharmaceutical dosage form in context, but the absence of an express active-ingredient limitation could create questions concerning written description, enablement, and claim scope.

A method-of-use claim generally presents a different infringement theory from a product claim. It may be asserted against a party that instructs or causes administration of the claimed dosage form, while product claims focus on the composition itself. Because the patent expired in 2000, claim 5 no longer creates current United States enforcement risk.

How strong was the patent estate for fast-dissolving dosage forms?

The patent was technically important but legally narrow in several respects.

Strengths

It claimed the combination of a solid oral dosage form and an open matrix.
It imposed a measurable rapid-disintegration threshold.
It covered both products and manufacturing processes.
It identified specific carrier materials associated with freeze-dried matrices.
It included a method-of-administration claim.
The claims were directed to a commercially relevant dosage-form platform rather than one active ingredient.

Limitations

The carrier list is closed by the "selected from the group consisting of" language.
The ten-second requirement creates a testing-dependent limitation.
Claim 2 requires sublimation from a solid composition in a mold.
The patent did not necessarily cover every orally disintegrating tablet.
It did not automatically cover later products using different polymers, compression technologies, granulation systems, or particle-engineering methods.
It did not protect a specific active pharmaceutical ingredient unless the active ingredient was included in a separately relevant claim or formulation patent.

The patent's historical importance should not be confused with present enforceability. Its claims cannot presently support a United States infringement action because the patent has expired.

When did U.S. Patent 4,371,516 lose exclusivity?

The ordinary patent term expired on February 1, 2000.

Event	Date
Issue	February 1, 1983
Ordinary statutory term	17 years from issue
Ordinary expiration	February 1, 2000
Post-expiration status	Public domain in the United States

The patent predates the modern 20-year term measured from the earliest effective nonprovisional filing date. Under the pre-1995 regime, the general rule was 17 years from grant. Patent-term adjustment under the current system generally does not change the analysis for a patent of this vintage.

There is no indication from the claim set that the patent was tied to a particular FDA-approved drug, so Hatch-Waxman patent-term extension under 35 U.S.C. § 156 would not ordinarily apply to the technology patent itself.

What is the Orange Book status of U.S. Patent 4,371,516?

U.S. Patent 4,371,516 is not an Orange Book listing by virtue of covering a dosage-form platform.

The Orange Book identifies patents submitted by sponsors for approved drug products under the Food and Drug Administration's patent-listing rules. A platform patent may be listed only if it meets the statutory and regulatory requirements for the relevant approved drug product, including requirements relating to drug substance, drug product, or approved method of use. A historical technology patent covering freeze-dried dosage forms does not automatically appear against every drug manufactured using that technology.

Paragraph IV relevance

A Paragraph IV certification is made in an ANDA against a listed patent for the reference product. Because U.S. Patent 4,371,516 expired in 2000, it cannot presently create a Paragraph IV stay or a valid patent-based barrier to an ANDA.

A generic applicant could still encounter later patents covering:

The active ingredient.
A specific dosage strength.
A particular freeze-dried composition.
A taste-masking system.
A stabilizer or excipient combination.
A blister package or moisture-barrier system.
A method of treating a disease.
A manufacturing process.
A specific orally disintegrating product.

Those later patents require separate Orange Book and litigation review.

Which later technologies compete with the claimed platform?

The fast-dissolving dosage-form field developed into several technically distinct platforms.

Platform type	Typical manufacturing approach	Relationship to Patent 4,371,516
Freeze-dried wafer	Molded aqueous composition followed by lyophilization	Closest technical relationship
Compressed orally disintegrating tablet	Compression of porous or rapidly disintegrating granules	Often outside the sublimation process claims
Effervescent tablet	Gas generation promotes breakup and dispersion	Different mechanism
Spray-dried dosage form	Spray drying of solution or suspension	Generally different process
Thin-film dosage form	Casting or coating polymeric films	Different dosage-form architecture
Molding technology	Molding and drying without claimed sublimation	Potentially outside claim 2
Particle-engineered tablet	Co-processed particles or porous excipients	Usually requires separate patent analysis

Commercial platforms associated with companies such as R.P. Scherer, Catalent, CIMA Labs, Eurand, Fuisz Technologies, and later owners of orally disintegrating tablet technologies developed around different combinations of porosity, compression, molding, taste masking, and drying.

The existence of a later platform patent does not establish infringement of Patent 4,371,516. The relevant questions are whether the later product uses the specified carrier, has the claimed open matrix, meets the ten-second water-disintegration limitation, and is made by sublimation from a solid molded composition.

What formulation patents may remain relevant after expiration?

Expiration of the foundational patent does not place every related technology in the public domain. Current freedom-to-operate analysis should separate the expired platform patent from later, potentially live patents.

Active-ingredient formulation patents

These may cover a specific drug in an orally disintegrating formulation, including:

Particle size.
Polymorphic form.
Salt or hydrate.
Stabilizer.
Taste-masking coating.
Dose uniformity.
Bioavailability.
Pharmacokinetic profile.

Method-of-use patents

A sponsor may hold a patent covering treatment of a disease with the active ingredient in a particular dosage form or patient population. Such patents may remain relevant to an ANDA even when the formulation technology patent has expired.

Manufacturing patents

Later patents may protect:

Freeze-drying cycle parameters.
Controlled nucleation.
Mold geometry.
Filling and freezing systems.
Residual-moisture limits.
Packaging under controlled humidity.
Automated removal and sealing.
Scale-up methods.

Packaging patents

Freeze-dried dosage forms are sensitive to mechanical damage and moisture. Later patent estates may cover:

Unit-dose blister systems.
Peelable foil structures.
Child-resistant packaging.
Moisture-barrier laminates.
Product extraction mechanisms.
Handling systems for fragile wafers.

What manufacturing and intellectual-property barriers remain?

The expired patent removes the central legal barrier, but commercial manufacture of a comparable dosage form still involves technical constraints.

Manufacturing barriers

Key process risks include:

Fragility during demolding and packaging.
Uneven active distribution.
Collapse of the porous matrix.
Residual moisture.
Long-term stability.
Dose variability at low active loadings.
Taste and mouthfeel.
Freeze-dryer capacity.
Cycle reproducibility.
Container-closure integrity.

A product can avoid the literal process claims while still requiring specialized lyophilization equipment, controlled freezing, low-humidity packaging, and validated handling systems.

Regulatory barriers

An orally disintegrating product may require demonstration of:

Assay and content uniformity.
Stability.
Dissolution.
Disintegration.
Mechanical integrity.
Microbial quality.
Impurity control.
Bioequivalence, where applicable.
Labeling consistency with the approved reference product.

FDA regulatory approval is independent of the expiration of Patent 4,371,516. A generic sponsor still must satisfy the applicable ANDA, 505(b)(2), or other pathway requirements.

Are biosimilar risks relevant to this patent?

No. Biosimilar litigation concerns biological products under the Biologics Price Competition and Innovation Act. Patent 4,371,516 covers a solid oral dosage-form technology and does not claim a biologic active ingredient, cell line, protein sequence, or biologic manufacturing process.

The relevant competitive pathway is generic or follow-on small-molecule development, not biosimilar development.

What licensing deals affected the technology?

The technology is historically associated with R.P. Scherer Corporation's freeze-dried oral dosage-form business, later associated with Catalent's Zydis platform. Commercial licensing and product-supply arrangements for particular drugs may have existed, but Patent 4,371,516 itself does not establish the terms of any license.

A license review should distinguish among:

A license to the expired patent.
A license to later improvement patents.
A technology-transfer agreement.
A contract-manufacturing agreement.
A trademark or brand license.
A license to proprietary equipment or process know-how.

Patent expiration does not terminate confidentiality obligations, trade-secret protection, quality agreements, or manufacturing know-how rights.

What patent litigation affects U.S. Patent 4,371,516?

The patent is no longer capable of supporting a current infringement action. Historical litigation may have involved the broader fast-dissolving dosage-form field, later platform patents, or product-specific patents, but the existence of litigation involving related technology would not extend the term of Patent 4,371,516.

There is no current Paragraph IV litigation risk from this patent. A litigation search should focus on later patents asserted against specific active ingredients or products, not on the expired patent as a standalone asset.

How should a generic launch be analyzed?

A generic or follow-on manufacturer can generally use the expired concepts disclosed and claimed by Patent 4,371,516, including:

Open porous matrices.
Freeze-dried oral dosage forms.
Rapid water disintegration.
Use of the listed carrier materials.
Sublimation-based preparation.
Molded unit-dose manufacture.

The launch analysis must then screen for later rights. A practical clearance sequence is:

Identify the target reference product and active ingredient.
Review current Orange Book listings.
Search later U.S. patents citing or improving the freeze-dried platform.
Map the proposed formulation against product claims.
Map the manufacturing process against process claims.
Review method-of-use patents and carve-out possibilities.
Screen packaging and device claims.
Assess expiration, terminal disclaimers, PTA, and any statutory exclusivity.
Review historical settlements and licenses involving the target product.
Confirm regulatory equivalence and product-specific labeling obligations.

The expired patent is therefore a low legal-risk item but a high technical-relevance document.

How does this patent compare with conventional orally disintegrating tablet patents?

Issue	U.S. Patent 4,371,516	Conventional compressed ODT patent
Structure	Open matrix network	Compressed porous or rapidly disintegrating tablet
Key carrier	Gelatin, hydrolysed dextran, alginate, or specified mixtures	Often broader excipient combinations
Manufacturing	Solidification and solvent sublimation	Compression, granulation, or molding
Disintegration threshold	Within 10 seconds in water	May use different time or test conditions
Mechanical strength	Often fragile	Usually higher tablet strength
Packaging	Frequently moisture- and impact-sensitive	Standard blister or bottle options may be available
Current enforceability	Expired	Depends on each later patent
Main commercial advantage	Rapid wetting and disintegration	Greater manufacturing flexibility and robustness

Key Takeaways

U.S. Patent 4,371,516 claims a freeze-dried, open-matrix oral dosage form that disintegrates in water within 10 seconds.
Claim 1 is limited by the open matrix, rapid-disintegration threshold, pharmaceutical dosage, and specified carrier materials.
Claim 2 requires sublimation of solvent from a solid composition held in a dosage-form mold.
Claims 3 and 4 narrow the process by adding optional excipients and specifying water as solvent.
Claim 5 covers oral administration and has a distinct method-of-use structure.
The patent's ordinary U.S. term expired on February 1, 2000.
The patent is not itself a current Orange Book barrier and cannot support a current Paragraph IV stay.
Biosimilar analysis is irrelevant because the patent concerns a small-molecule oral dosage-form platform.
Later patents may still cover active ingredients, specific formulations, manufacturing cycles, packaging, taste masking, or methods of use.
The patent is historically important for the Zydis-style freeze-dried dosage-form platform but has no current blocking force in the United States.

FAQs About U.S. Patent 4,371,516

Can a company still practice the technology disclosed in U.S. Patent 4,371,516?

Yes. The patent expired in 2000, so the claimed technology is generally available for practice in the United States, subject to later patents and other enforceable rights.

Does a fast-dissolving tablet infringe this patent automatically?

No. The product must satisfy the specific claim limitations, including the open matrix, ten-second water-disintegration threshold, and specified carrier system. A conventional compressed orally disintegrating tablet may not meet those limitations.

Does the patent cover Zydis products sold today?

It may describe technology historically associated with Zydis, but the patent itself no longer provides enforceable exclusivity. Current Zydis products may be covered by later patents, trademarks, know-how, or product-specific rights.

Does expiration eliminate FDA approval requirements?

No. Patent expiration affects exclusivity, not regulatory approval. A manufacturer must still comply with the applicable FDA pathway and demonstrate product quality, stability, performance, and bioequivalence where required.

Can the patent be challenged through a Paragraph IV certification?

No current Paragraph IV challenge is needed against this expired patent. Paragraph IV certifications address listed patents that remain relevant to an ANDA. Later unexpired patents may still require certification or other regulatory treatment.

References

United States Patent and Trademark Office. (1983). Pharmaceutical compositions (U.S. Patent No. 4,371,516).
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Refuse-to-receive standards. U.S. Department of Health and Human Services.
United States Code. (2024). 35 U.S.C. §§ 154, 156, and 271. Cornell Law School, Legal Information Institute.
Code of Federal Regulations. (2024). 21 C.F.R. § 314.53: Submission of patent information. U.S. Government Publishing Office.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	41483/77	Oct 06, 1976

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2882577	⤷ Start Trial
Australia	513845	⤷ Start Trial
Belgium	859291	⤷ Start Trial
Canada	1083042	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 4,371,516