U.S. Patent 5,866,166: Claim Scope, Expiration, and Silicified Microcrystalline Cellulose Patent Landscape

U.S. Patent No. 5,866,166 covers co-processed pharmaceutical excipients made from microcrystalline cellulose and a compressibility-augmenting material, particularly colloidal silicon dioxide and certain surfactants. The patent reaches compositions, aqueous slurries, wet-granulated excipient-active mixtures, and tablet-manufacturing processes.

The patent is expired. Its practical importance is historical and commercial: it helped establish the patent position around silicified microcrystalline cellulose, including products marketed for direct compression and wet granulation. The claims do not protect a therapeutic drug, API, or finished drug product. They are not Orange Book-listed drug patents and do not create FDA market exclusivity.

What does U.S. Patent 5,866,166 protect?

The patent protects a co-processed excipient in which microcrystalline cellulose and a compressibility-augmenting agent are present in intimate association within agglomerated particles.

The central technical theory is that the added material prevents or reduces cellulose-to-cellulose interaction during drying and compression. The claims describe two related mechanisms:

Physically restricting the proximity of interfaces between adjacent cellulose surfaces.
Physically restricting those interfaces and inhibiting interactions, including hydrogen bonding, between cellulose surfaces.

The patent differs from a conventional physical blend. Its claim language focuses on an agglomerated or co-processed structure created through an aqueous slurry and controlled drying, rather than simply mixing MCC with silica immediately before tableting.

Patent identification and legal status

Item	Data
Patent	U.S. Patent No. 5,866,166
Title	Compressible pharmaceutical excipients and methods of making same
Issue date	February 2, 1999
Principal technology	Co-processed MCC with compressibility-augmenting agents
Primary assignee	FMC Corporation, based on the issued patent record
Earliest relevant priority	1996, based on the patent family record
Patent term	Expired
Expected ordinary term endpoint	Approximately February 2017, subject to the official USPTO term calculation
Orange Book status	Not an Orange Book-listed drug patent
FDA drug exclusivity	None created by this patent
Current enforceability	No enforceable exclusionary term remains

The exact expiration date should be taken from the USPTO patent-term record because patent-term adjustment, terminal disclaimers, or continuity information can affect the calculation. The patent is nevertheless beyond its enforceable term.

How many independent claims does U.S. Patent 5,866,166 have?

The issued claims contain multiple independent claim categories. The principal independent claims are claims 1, 13, 19, 22, 26, 27, 32, 35, and 36.

Claim	Claim category	Core subject matter
1	Composition	MCC plus a compressibility-augmenting agent in intimate association
13	Aqueous slurry	MCC, augmenting agent, and specified solids content
19	Solid dosage form	Compressed excipient and therapeutically active ingredient
22	Method	Slurry formation, drying, and wet granulation
26	Method	Slurry formation, drying, wet granulation, and tablet compression
27	Composition	MCC plus a highly polar molecule or surfactant
32	Aqueous slurry	MCC plus highly polar molecule or surfactant
35	Solid dosage form	Compressed mixture containing the claim 27 excipient
36	Compressible granulate	Co-processed MCC, augmenting agent, and active agent

The claims should be divided into two principal subfamilies:

Claims 1 through 26: broad mechanism-based claims, with particular emphasis on silicon dioxide.
Claims 27 through 45: claims directed to surfactants and highly polar compounds, including specific HLB ranges and named materials.

What formulations are protected by the patent?

The strongest formulation coverage is directed to agglomerated MCC containing colloidal silicon dioxide or another material that changes cellulose surface interaction.

Silicon dioxide formulations

Claims 3, 4, 6, 7, 10, 16, 18, and 20 narrow the silicon dioxide embodiment by specifying:

Average primary particle size of about 1 nm to 100 micrometers.
Colloidal silicon dioxide.
Silicon dioxide concentration of about 0.1% to 20% by weight of MCC.
A narrower colloidal silica range of about 1.25% to 5% by weight of MCC.
Silicon dioxide surface area of about 10 m²/g to 500 m²/g.

The commercial relevance is the claimed combination of MCC and colloidal silica in a co-processed agglomerate. A product containing the same ingredients as a simple dry blend would not necessarily satisfy the structural limitation requiring intimate association in agglomerated particles.

Surfactant formulations

Claims 27 through 45 cover an alternative technical route. The augmenting agent can be:

A surfactant.
A highly polar molecule.
A surfactant with an HLB value of at least 10.
A surfactant with an HLB value of about 15 to 50.
Sodium lauryl sulfate.
Polysorbate 40.
Certain highly polar dyes.

The claims also specify surfactant concentrations of about 0.1% to 0.5% by weight of MCC. Claim 45 narrows the HLB range to approximately 15 to 50.

The surfactant claims are commercially significant because they extend beyond silica-based excipients. They attempt to capture the functional use of polar or surface-active materials to reduce cellulose bonding during aqueous processing and drying.

Other claimed additives

Claims 9, 25, and 31 identify additional materials that can be present in the agglomerate or slurry:

Non-silicon metal oxides.
Starches and starch derivatives.
Polyalkylene oxides.
Stearic acid.
Kaolin.
Polydimethylsiloxane.
Silica gel.
Diatomaceous earth.
Mixtures of these materials.

These claims are narrower because they depend on the broader composition claims. They do not independently protect every formulation containing one of these materials. The formulation must still satisfy the underlying MCC, augmenting-agent, agglomeration, and functional limitations.

What manufacturing processes are protected?

The principal manufacturing concept is aqueous co-processing followed by drying in a way that inhibits quasi-hornification or excessive cellulose-to-cellulose hydrogen bonding.

Claimed process sequence

Claims 5, 22, and 26 generally require:

Preparing an aqueous slurry containing MCC and the augmenting agent.
Drying the slurry to form agglomerated particles.
Maintaining intimate association between MCC and the augmenting agent.
Wet granulating the excipient with an active ingredient.
Compressing the resulting mixture into tablets, where claim 26 applies.

Claim 44 identifies spray drying as a claimed drying technique. Claims 23 and 24 add particle-size and moisture limitations:

Average particle size: about 10 to 1,000 micrometers.
Moisture content: about 0.5% to 15%.

Claims 13 through 18 and 32 through 34 cover the slurry stage. The claimed total solids content is:

About 0.5% to 25% generally.
About 15% to 20% in dependent claims.
About 17% to 19% in narrower dependent claims.

The process claims matter because the final excipient may be chemically identical to a conventional mixture while having a different particle architecture and compression profile. A manufacturer using a materially different process could avoid a process claim, although the resulting product could still raise issues under a composition claim if the product limitations are met.

How broad are the composition claims?

Claim 1 is the principal broad composition claim. It requires:

Microcrystalline cellulose.
A compressibility-augmenting agent.
A functional effect involving cellulose-surface proximity or interaction.
Agglomerated particles.
Intimate association between MCC and the augmenting agent.

The claim does not require silicon dioxide. Silicon dioxide is introduced through dependent claims 3, 4, 6, 7, 10, 16, 18, and 20.

Claim 27 creates a separate composition platform. It requires:

MCC.
An agent that inhibits interactions between cellulose surfaces.
Either a highly polar molecule or a surfactant.
For the surfactant embodiment, a concentration of about 0.1% to 0.5% by weight of MCC.
Agglomerated particles with the MCC and agent in intimate association.

Claims 1 and 27 overlap conceptually but are not identical. Claim 1 is framed around both physical spacing and interaction inhibition. Claim 27 is framed around inhibition of interactions and specifically identifies highly polar molecules and surfactants.

Key claim limitations

Limitation	Commercial significance
Microcrystalline cellulose	Excludes excipients based solely on other cellulose derivatives
Compressibility-augmenting agent	Requires more than an arbitrary additive
Functional mechanism	Creates potential claim-construction and proof issues
Agglomerated particles	Favors co-processed materials over simple blends
Intimate association	Requires evidence about particle structure or manufacturing
Aqueous slurry	Central to process claims
Controlled drying	Relevant to quasi-hornification and hydrogen-bond reduction
Particle-size range	Provides narrower product boundaries
Moisture range	Creates an additional quality-control limitation
Wet granulation	Limits certain dosage-form and manufacturing claims
Therapeutically active ingredient	Relevant only to dosage-form and granulate claims

What are the principal claim vulnerabilities?

The patent’s strongest commercial concept is clear, but several limitations create potential validity or infringement issues.

Functional language

Terms such as “compressibility augmenting agent,” “effective amount,” “physically restricts the proximity,” “inhibits interactions,” and “intimate association” are functional or qualitative. Their application may depend on the specification, experimental data, and the ordinary meaning of the terms at the relevant filing date.

A challenger could argue that the claims lack adequate objective boundaries. The patent owner would likely rely on compression testing, particle characterization, formulation performance, and the specification’s examples to establish meaning.

Breadth of “highly polar molecule”

Claims 27, 32, 35, 41, and 42 use the category “highly polar molecule.” That category is potentially broad. Claims 37 through 40 narrow it through surfactant HLB or named surfactants, while claim 42 identifies particular dyes.

The broad “highly polar molecule” language may face written-description, enablement, or indefiniteness scrutiny if it is applied to compounds not demonstrated in the specification. The narrower named-compound and HLB claims are easier to evaluate but cover less territory.

Product-by-process and process dependence

Several claims combine a composition with a preparation method, including aqueous slurry formation and drying. A dispute could turn on whether the manufacturing steps limit the product itself or merely describe how the product is made. The answer depends on the precise claim language and governing case law.

For a current commercial product, the critical questions would include:

Whether it is a co-processed agglomerate or a physical blend.
Whether silica is located within the MCC particle structure.
Whether the product has the claimed particle-size and moisture attributes.
Whether the product exhibits the claimed compressibility effect.
Whether the accused process uses an aqueous slurry and controlled drying.

Claim 36 drafting irregularity

Claim 36 refers to “monocrystalline cellulose,” while the broader claim set consistently uses “microcrystalline cellulose.” On the supplied text, “monocrystalline cellulose” appears to be a transcription or drafting error. Its effect would depend on the official issued patent text and any prosecution-history correction. It should not be treated as interchangeable with “microcrystalline cellulose” without reviewing the official record.

When did U.S. Patent 5,866,166 lose exclusivity?

The patent lost enforceable exclusivity when its statutory term ended, approximately 20 years after the applicable nonprovisional filing or priority date. Based on the patent’s 1996 priority and 1997 filing history, the ordinary term ended around 2017.

The following rights should be distinguished:

Right	Status
Patent exclusionary rights	Expired
FDA small-molecule exclusivity	Not applicable
Orange Book listing	Not applicable
Paragraph IV challenge	Not applicable to this excipient patent itself
Biosimilar litigation risk	Not applicable
Trade-secret protection	Potentially available for undisclosed manufacturing know-how
New patents on improved excipients	Potentially available if independently patentable

Because the patent is expired, a manufacturer does not face a current injunction or damages claim based solely on practicing the expired claims. A company may still need to assess later patents covering a specific commercial product, manufacturing equipment, particle morphology, formulation, or branded excipient.

Does the patent have Orange Book or FDA exclusivity significance?

No. U.S. Patent 5,866,166 protects an excipient technology, not an approved drug substance or drug product.

The FDA Orange Book lists patents submitted for approved drug products under the Hatch-Waxman framework. An excipient patent of this type generally does not create:

New chemical entity exclusivity.
Five-year NCE exclusivity.
Three-year clinical-investigation exclusivity.
Pediatric exclusivity.
Orphan-drug exclusivity.
A patent-listed Paragraph IV barrier.

A drug manufacturer using silicified MCC would ordinarily address excipient safety, quality, identity, functionality, and suitability in its regulatory submission. The patent itself does not control FDA approval.

Are Paragraph IV challenges or generic launches affected?

No direct Paragraph IV challenge is associated with this patent because it is not a drug-product patent listed in the Orange Book.

The technology can nevertheless affect generic development commercially. Generic manufacturers may use:

Conventional MCC.
Silicified MCC.
Alternative co-processed excipients.
Dry-blended silica and MCC.
Starch-based or coprocessed compression aids.
Direct-compression formulations that avoid wet granulation.

For a generic drug, the relevant IP risk would usually arise from patents covering the API, dosage form, formulation, method of treatment, release profile, device, or manufacturing process. U.S. Patent 5,866,166 would not ordinarily create a current barrier because it is expired.

Which companies and products are relevant to the patent landscape?

The patent is associated with the development of silicified microcrystalline cellulose, historically linked to FMC Corporation and the commercial excipient later known in the market as Prosolv. The commercial field also includes JRS Pharma’s excipient portfolio and other suppliers of direct-compression MCC, coprocessed excipients, and silica-containing tableting aids.

Relevant competitive categories include:

Category	Examples of competitive approach
Conventional MCC	Avicel-type microcrystalline cellulose
Silicified MCC	MCC co-processed with colloidal silicon dioxide
Co-processed cellulose systems	MCC combined with starch, mannitol, or other binders
Dry blends	MCC and colloidal silica blended during formulation
Wet-granulation excipients	MCC systems optimized for granulation and tablet strength
Direct-compression excipients	Products designed to improve flow, compactability, and tensile strength

The expired patent should be treated as foundational prior art in freedom-to-operate analyses. Newer patents may still protect particular particle structures, silica distributions, spray-drying conditions, moisture levels, grades, or multi-excipient combinations.

How strong is the patent estate today?

The patent estate surrounding U.S. Patent 5,866,166 has limited direct blocking strength because the patent is expired. Its historical scope was substantial because it covered both:

A composition platform based on co-processed MCC and a compressibility-enhancing agent.
Manufacturing and dosage-form applications using that excipient.

Its strongest historical claims were likely the narrower silicon-dioxide claims and the process claims tied to aqueous slurry preparation and controlled drying. Its broader mechanism-based claims were more exposed to disputes over claim boundaries and proof of functional performance.

Strength assessment

Factor	Assessment
Technical centrality	High for silicified MCC technology
Historical commercial relevance	High
Current exclusionary value	None after expiration
Prior-art significance	High
Ease of proving composition infringement	Moderate to difficult, depending on particle characterization
Ease of proving process infringement	Depends on manufacturing records and process analytics
Risk from simple dry blending	Lower than risk from co-processing, subject to claim construction
Risk from later patents	Requires separate family-by-family review
Regulatory relevance	Low as a standalone patent
Licensing relevance	Historical or know-how-based rather than patent-exclusionary

What manufacturing and IP barriers remain after expiration?

Patent expiration removes the principal legal barrier, but commercial and technical barriers remain.

A supplier seeking to commercialize a comparable excipient may need to control:

MCC source and degree of polymerization.
Silica grade, surface area, and particle-size distribution.
Slurry viscosity and solids concentration.
Dispersion stability.
Spray-drying or other drying conditions.
Residual moisture.
Particle morphology and bulk density.
Flowability and compressibility.
Tablet tensile strength and friability.
Disintegration and dissolution performance.
Excipient consistency across manufacturing sites.

These parameters may be protected through trade secrets, confidential process specifications, quality agreements, trademarks, or later patent filings. Patent expiration does not place a supplier’s confidential manufacturing information in the public domain.

What generic entry risks exist for products using this technology?

For a product using the technology as an excipient, the patent-specific generic entry risk is low because the patent is expired and is not an Orange Book-listed barrier.

The principal risks shift to:

Later patents covering the specific excipient grade.
Drug-product patents using the excipient in a claimed formulation.
Method-of-treatment patents.
Modified-release or abuse-deterrent dosage-form patents.
Bioequivalence failure caused by different excipient functionality.
Supplier qualification and regulatory comparability.
Manufacturing trade secrets and contractual restrictions.

A generic company can generally select an alternative excipient, but substitution may alter tablet hardness, dissolution, disintegration, content uniformity, and scale-up performance.

How does this patent compare with later excipient patents?

U.S. Patent 5,866,166 is broad at the platform level. It claims the relationship between MCC and an augmenting agent, plus the co-processing route.

Later excipient patents typically narrow the invention around one or more of the following:

Defined particle morphology.
Specific silica loading.
Controlled surface-area ratios.
Spray-drying parameters.
Moisture content.
Bulk and tapped density.
Flowability.
Tablet tensile strength.
Specific API-excipient combinations.
Improved dissolution or disintegration.
A particular commercial grade.

The practical FTO question is therefore not whether a new product resembles the expired patent. It is whether the product falls within an unexpired continuation, divisional, improvement patent, or third-party patent family.

Key Takeaways

U.S. Patent 5,866,166 covers co-processed MCC excipients containing materials that improve compressibility by reducing cellulose-surface interaction.
Colloidal silicon dioxide is the central claimed embodiment, with disclosed ranges including approximately 0.1% to 20% and, in narrower claims, 1.25% to 5% based on MCC.
The patent also covers surfactants, highly polar molecules, sodium lauryl sulfate, polysorbate 40, and specified dyes.
The claims extend to compositions, aqueous slurries, wet-granulated excipient-active mixtures, granulates, and tablet-making methods.
Agglomeration and intimate association distinguish the claimed technology from a simple dry blend.
The patent expired approximately in 2017 and has no current exclusionary effect.
It is not an Orange Book-listed patent and does not create Hatch-Waxman exclusivity or a Paragraph IV barrier.
Current FTO risk must focus on later patents, commercial-grade improvements, drug-product patents, and confidential manufacturing know-how.
Claim 36 contains an apparent “monocrystalline cellulose” drafting inconsistency that requires reference to the official issued patent and prosecution history.
The patent remains important as prior art and as a historical foundation for silicified microcrystalline cellulose products.

FAQs

Can a company manufacture silicified microcrystalline cellulose after U.S. Patent 5,866,166 expired?

Yes. Expiration removes the patent’s exclusionary rights. The company must still evaluate later patents, trademarks, contracts, regulatory requirements, and trade-secret risks.

Does using colloidal silicon dioxide with MCC automatically infringe the patent?

No. The claims require more than the presence of both ingredients. Several claims require agglomerated particles and intimate association, while others impose functional, concentration, particle-size, slurry, or process limitations.

Is Prosolv still protected by U.S. Patent 5,866,166?

The patent itself no longer provides enforceable protection. A particular Prosolv grade may have separate protection through later patents, trademarks, confidential manufacturing information, or supplier contracts.

Can a generic drug applicant use this excipient without a Paragraph IV certification?

This patent itself ordinarily does not require a Paragraph IV certification because it is not an Orange Book-listed drug patent. Certifications depend on the patents listed for the specific reference drug product.

Does the patent cover tablets containing any active pharmaceutical ingredient?

Claims 19, 21, 22, 26, 28, 35, and 36 reach certain excipient-active mixtures and wet-granulated or compressed dosage forms. They do not cover every tablet containing MCC. The claimed excipient structure, agent, process, and other limitations must be met.

References

U.S. Patent No. 5,866,166. (1999). Compressible pharmaceutical excipients and methods of making same. United States Patent and Trademark Office.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Code, 35 U.S.C. § 154. Patent term.
United States Code, 21 U.S.C. § 355. New drug applications and abbreviated applications.

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Details for Patent: 5,866,166

Summary for Patent: 5,866,166