United States Drug Patent 4,465,660: Claim Scope, Expiration, Orange Book Status, and Theophylline Patent Landscape

U.S. Patent No. 4,465,660 protects a highly specific sustained-release theophylline tablet. Its core limitations are a very high theophylline loading, a low level of tableting lubricant, controlled dissolution without disintegration, a tablet thickness of approximately 0.08 to 0.12 inches, and opposing-face scoring that permits both dose-bisection and dose-trisection. The patent issued on August 14, 1984, and expired on August 14, 2001, under the pre-Uruguay Round patent term applicable to the patent. It does not create a current U.S. barrier to generic theophylline extended-release tablets.

The patent is commercially important as a formulation and dosage-flexibility patent, not as a current exclusivity right. Its claims are narrower than a general sustained-release theophylline formulation claim because they require a combination of composition, physical geometry, release behavior, pharmacokinetics, and scoring features.

What does U.S. Patent 4,465,660 cover?

The patent covers sustained-release tablets containing theophylline as the dominant tablet component. The broadest claims require:

Limitation	Claims containing the limitation
At least 95% theophylline by weight	1, 11
99.4% to 99.8% theophylline	9, 22
99.6% theophylline and 0.4% magnesium stearate	6, 18
100 mg to 500 mg theophylline	2, 12
300 mg theophylline	7, 19
Tablet thickness of 0.08 to 0.12 inches	1, 9, 11
Narrower thickness of 0.09 to 0.11 inches	3, 14
Approximately 0.1-inch thickness	23
Magnesium stearate as lubricant	4-6, 10, 16-18, 22
Tablet remains intact during dissolution	1, 9
Dissolves without first disintegrating	11
83% to 100% dissolution over about four hours	11
Blood concentration of approximately 10 to 20 mcg/mL	1, 9, 11
8- to 12-hour or 12-hour dosing interval	1, 11, 13
Bisect scoring on one face	1, 9, 11, 20
Trisect scoring on the opposing face	1, 9, 11, 20
Rectangular edge walls	8, 21, 23

The patent therefore does not broadly cover every theophylline extended-release product. A potentially infringing product would need to satisfy the relevant claim limitations as a combination.

How are the independent claims different?

Claim 1: High-theophylline tablet with pharmacokinetic and scoring limitations

Claim 1 requires a sustained-release tablet containing 95% to 99.8% theophylline by weight, with the balance consisting of conventional tablet ingredients. The formulation must produce a tablet that remains intact during dissolution.

The claim also requires:

A pair of substantially planar opposing faces;
Edge walls connecting the faces;
Thickness from 0.08 to 0.12 inches;
A 12-hour dosing interval;
Continuous serum theophylline concentration from 10 to 20 mcg/mL; and
A bisect score on one face and two trisect scores on the opposite face.

The claim is unusually multidimensional. It is not limited to composition. It incorporates tablet architecture, release behavior, dosing performance, and score placement.

Claim 9: Narrow composition claim

Claim 9 narrows the composition to:

99.4% to 99.8% theophylline; and
0.1% to 0.6% tableting lubricant.

It retains the tablet geometry, thickness, serum-concentration, dissolution-intactness, and scoring requirements of the broader claim structure. Claim 10 expressly identifies magnesium stearate as the lubricant.

This is a composition-focused claim, but it remains dependent on physical and functional limitations. A tablet containing 99.6% theophylline and 0.4% magnesium stearate would not necessarily infringe claim 9 unless it also satisfies the required thickness, scoring, dissolution, and serum-concentration limitations.

Claim 11: Dissolution-focused claim

Claim 11 uses a different technical definition of the dosage form. It requires a tablet containing at least 95% theophylline that:

Dissolves without first disintegrating when contacted with water;
Dissolves to 83% to 100% by weight over about four hours;
Maintains a therapeutically effective serum concentration for up to 12 hours;
Has a thickness of 0.08 to 0.12 inches; and
Has score lines arranged for both bisecting and trisecting the tablet.

Claim 11 is potentially broader than claim 1 in some compositional respects because it does not require the specific 10 to 20 mcg/mL concentration range in the same wording. It is narrower in requiring the specified dissolution performance.

What formulations are protected by U.S. Patent 4,465,660?

The strongest formulation position is the subject matter of claims 6 and 18:

99.6% theophylline;
0.4% magnesium stearate;
300 mg theophylline in claims 7 and 19; and
The required tablet geometry and scoring inherited from claims 1 or 11.

The patent's formulation concept minimizes excipients. The active pharmaceutical ingredient performs much of the structural and release-function work, while magnesium stearate acts as the principal lubricant. The claims do not require a polymeric matrix, enteric coating, membrane coating, pellet system, or multiparticulate delivery system.

That feature distinguishes the patent from many extended-release formulations that rely on:

Hydrophilic polymers;
Wax matrices;
Coated beads or pellets;
Insoluble matrix formers;
Osmotic systems; or
Layered tablets.

A product with a substantial polymer matrix could avoid the high-theophylline and lubricant-ratio limitations, even if it provides a similar 8- or 12-hour pharmacokinetic profile.

How strong is the patent estate for the claimed tablet?

The patent estate is narrow but technically coherent. Its strongest features are the combination of precise physical limitations and a distinctive scoring configuration.

Strength factor	Assessment
Composition specificity	Strong against tablets with very high theophylline loading and low magnesium stearate content
Tablet geometry	Strong if the accused product falls within the stated thickness range
Scoring configuration	Strong because opposite-face bisect and trisect scoring is unusual
Dissolution limitation	Fact-intensive and potentially vulnerable to testing methodology
Pharmacokinetic limitation	Difficult to assess from the product alone and dependent on clinical or bioequivalence data
Claim breadth	Limited by multiple cumulative limitations
Current enforceability	None; the patent expired in 2001
Design-around potential	High for products using different excipient systems, thicknesses, scoring, or release mechanisms

The patent would have been more difficult to design around if it had focused only on the high active loading and sustained-release profile. Its scoring and thickness limitations create clear noninfringement pathways.

When did U.S. Patent 4,465,660 lose exclusivity?

U.S. Patent 4,465,660 issued on August 14, 1984. Because it falls under the pre-June 8, 1995 patent-term regime, its statutory term was generally 17 years from issuance rather than 20 years from the earliest effective nonprovisional filing date. The patent expired on August 14, 2001, subject to the standard statutory term calculation applicable to the patent. [1]

The expiration means:

The claimed tablet can be made and sold in the United States without a patent license;
Patent-based generic launch restrictions tied to this patent ended in 2001;
A Paragraph IV challenge to this patent is no longer commercially relevant;
A 30-month stay based solely on this patent cannot presently block an ANDA; and
Any current commercial dispute would need to rely on other unexpired patents, regulatory exclusivity, trade secrets, contract rights, or nonpatent claims.

What is the Orange Book status of U.S. Patent 4,465,660?

The Orange Book lists patents submitted by an NDA holder as covering an approved drug substance, drug product, or method of use. FDA patent listing does not determine validity, enforceability, or infringement. [2]

For a patent issued in 1984 and expired in 2001, the operative Orange Book position is that it cannot create a current patent-based barrier to generic approval or launch. Any historical listing would now have no blocking effect because the patent term has ended.

The relevant regulatory distinction is:

Issue	Effect of Patent 4,465,660 today
Historical Orange Book listing	May have existed depending on NDA-holder submissions
Current patent term	Expired
ANDA Paragraph IV challenge	No practical need against an expired patent
30-month stay	Not available as a current blocking mechanism based on this patent
FDA approval standard	Independent of the expired patent
Generic approval	Controlled by applicable ANDA requirements and any other active patents or exclusivities

FDA approval of an extended-release theophylline product does not establish infringement or noninfringement of this patent. The patent's expiration removes the principal legal consequence.

What patent litigation affects U.S. Patent 4,465,660?

No current litigation can be based on the enforceable patent rights in U.S. Patent 4,465,660 because the patent expired more than two decades ago. Historical infringement litigation, if any, would have been subject to the patent's then-current term and to the technical proof required for each claim.

The most important litigation issues would have been:

Whether the accused tablet fell within the 0.08- to 0.12-inch thickness range.
Whether the tablet remained intact rather than disintegrating during dissolution.
Whether the composition contained at least 95% theophylline.
Whether the lubricant concentration fell within the claimed range.
Whether the opposite faces carried the required bisect and trisect scores.
Whether the product achieved the specified serum concentration or dissolution result.
Whether claim terms such as "conventional pharmaceutical tablet ingredients" and "selected to provide" were definite and adequately supported.

Because the claims combine structural and functional requirements, infringement would likely have required product testing, manufacturing records, dissolution data, labeling, and pharmacokinetic evidence. A formulation that meets the composition limitations but uses a different scoring design or thickness could present a substantial noninfringement position.

What generic entry risks exist for the claimed product?

The direct patent risk from U.S. Patent 4,465,660 is zero because the patent expired in 2001. Generic entry risk instead depends on product-level factors:

Whether the reference listed drug has an approved extended-release dosage form;
Whether the generic must demonstrate bioequivalence under an ANDA;
Whether FDA has identified other active patents for the relevant NDA;
Whether the generic uses the same strength and release characteristics;
Whether the sponsor relies on Paragraph III certification for unexpired patents; and
Whether formulation differences create therapeutic-equivalence or substitutability issues.

Theophylline is a small-molecule drug. It has no biosimilar pathway exposure. Generic manufacturers use the ANDA pathway, not the abbreviated biosimilar pathway under the Public Health Service Act. [3]

The principal commercial challenge for an extended-release theophylline generic is bioequivalence, not the expired patent. Extended-release dosage forms can require comparative pharmacokinetic testing across fed and fasted conditions, depending on FDA product-specific guidance and the reference product's labeling.

How does this patent compare with competing theophylline patent strategies?

Patent strategy	Typical technical focus	Relationship to Patent 4,465,660
High-active-loading tablet	Theophylline concentration, lubricant level, tablet structure	Directly aligned with Patent 4,465,660
Polymer matrix tablet	Hydrophilic or hydrophobic release-control excipients	Potential design-around
Coated multiparticulates	Beads, pellets, membrane coatings	Generally outside the claimed tablet structure
Osmotic delivery	Semipermeable membrane and osmotic core	Technically distinct
Enteric or delayed release	pH-dependent release	Different release objective
Method-of-use patent	Dosing, asthma treatment, serum-level control	Separate legal category
Manufacturing patent	Compression force, granulation, tooling, or coating process	May create separate process risk
Device or score design	Dose splitting and tablet handling	Relevant to the patent's scoring limitations

The patent is therefore best understood as a specialized immediate-compression or high-load matrix-tablet patent. It is not a platform patent covering all sustained-release theophylline technology.

Are there formulation, method-of-use, or manufacturing barriers remaining?

Formulation patents

The expired patent does not prevent use of its claimed composition. A current formulation patent would need a later filing date and an unexpired term. Potentially relevant later rights would concern a specific dosage form, release mechanism, excipient combination, or bioavailability profile rather than the expired claim set itself.

Method-of-use patents

Claim 13 refers to administering the tablet at intervals of approximately 8 to 12 hours to maintain bronchodilative concentrations. It remains a dependent product claim, not a standalone method-of-treatment claim in the wording provided. It does not create an active method-of-use right today because the underlying patent has expired.

Manufacturing and process patents

The claims provided do not expressly claim:

A granulation process;
A compression-force profile;
A tooling process;
A coating operation;
A dissolution-testing apparatus; or
A manufacturing facility or batch process.

A later process patent could create separate risk, but Patent 4,465,660 itself does not retain enforceable manufacturing exclusivity.

Which companies challenged or competed around the patent?

The commercial market included branded and generic extended-release theophylline products marketed under names such as Theo-Dur, Theo-24, Uniphyl, and related generic products. Brand ownership and manufacturing arrangements changed over time, and product-specific patent positions depended on the relevant NDA, formulation, and Orange Book submissions.

The patent record itself does not establish a current licensing arrangement or a current challenge by a particular generic company. Patent assignment does not prove that a license was granted, and an FDA-approved generic does not prove that it practiced the patented claims during the patent term.

The competitive landscape after 2001 was shaped by:

Low barriers to active-ingredient sourcing;
Expiration of formulation patents;
Multiple approved extended-release presentations;
Declining clinical use of theophylline relative to inhaled bronchodilators and corticosteroids; and
Generic price competition.

What was the likely revenue exposure?

The patent's commercial value was tied to extended-release theophylline tablets, particularly 300 mg and potentially other strengths within the 100 mg to 500 mg range. The patent did not cover all theophylline sales, immediate-release tablets, liquid formulations, injectable products, inhaled products, or unrelated bronchodilator products.

Revenue exposure would therefore have depended on:

The market share of the specific high-load sustained-release tablet;
Whether the branded product used the claimed scoring configuration;
The number of approved generic competitors;
The timing of generic approval; and
Whether later patents or exclusivity rights covered the marketed product.

By 2001, the patent expiration removed the principal patent premium. The economic effect would have been greatest for a branded extended-release product that had relied on the tablet's differentiated dosing and scoring features.

Key Takeaways

U.S. Patent 4,465,660 covers a specific high-theophylline sustained-release tablet, not the full class of extended-release theophylline products.
The core limitations are 95% or more theophylline, narrow tablet thickness, intact or non-disintegrating dissolution, 8- to 12-hour therapeutic performance, and opposing-face bisect/trisect scoring.
Claims 6, 7, 18, and 19 focus on the narrow 99.6% theophylline and 0.4% magnesium stearate formulation, including a 300 mg strength.
The patent issued August 14, 1984, and expired August 14, 2001.
It has no current blocking force against generic theophylline products.
The patent has no biosimilar relevance because theophylline is a small-molecule active ingredient.
Historical infringement analysis would have required detailed testing of composition, thickness, scoring, dissolution, and pharmacokinetic performance.
A polymer matrix, coated multiparticulate, osmotic, or differently scored tablet could have provided design-around opportunities during the patent term.
Current commercial risk depends on later patents, FDA requirements, bioequivalence, and product-specific regulatory status rather than Patent 4,465,660.

FAQs About U.S. Patent 4,465,660

Is U.S. Patent 4,465,660 still enforceable?

No. The patent expired on August 14, 2001.

Does the patent cover all 12-hour theophylline tablets?

No. A product must meet the applicable claim's composition, geometry, scoring, dissolution, and functional limitations.

Does a 300 mg extended-release theophylline tablet infringe automatically?

No. The 300 mg limitation is only one element of dependent claims 7 and 19. Other inherited limitations must also be satisfied.

Is magnesium stearate required in every claim?

No. Magnesium stearate is expressly required in certain dependent claims and in the narrow composition claims, but the broader independent claims allow conventional pharmaceutical ingredients meeting the other requirements.

Can a generic manufacturer rely on patent expiration instead of filing Paragraph IV?

For this expired patent, a Paragraph IV challenge is unnecessary. The manufacturer must still address any other unexpired patents and meet FDA approval requirements for the applicable extended-release product.

References

United States Patent and Trademark Office. (1984). U.S. Patent No. 4,465,660, sustained release theophylline tablet.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2023). Abbreviated new drug application process.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	380789	⤷ Start Trial
Austria	A202081	⤷ Start Trial
Australia	549299	⤷ Start Trial
Australia	7020581	⤷ Start Trial
Belgium	888697	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,465,660

Summary for Patent: 4,465,660