US Patent 4,517,179: Claim Scope, Expiration, and Pharmaceutical Patent Landscape

US Patent 4,517,179 protects a rapidly dissolving solid oral dosage composition for low-solubility drugs. Its core combination is a finely sized drug, microcrystalline cellulose, unmilled or coarse-milled dibasic calcium phosphate, starch, and a fatty lubricant. The patent specifically covers metolazone and triamterene embodiments, particle-size limitations, formulation ranges, tablet strengths, and a manufacturing process.

The patent issued on May 14, 1985. Assuming no unusual term adjustment or extension, its 17-year term for a pre-Uruguay Round patent expired on May 14, 2002. The claims are therefore no longer enforceable in the United States. The commercial significance of US 4,517,179 is historical and technical rather than an active barrier to generic entry.

What does US Patent 4,517,179 protect?

The patent protects a formulation platform designed to improve dissolution of poorly water-soluble drugs in tablets or capsules. The principal claim requires all of the following:

Required element	Claim 1 requirement
Drug type	Low-solubility drug
Drug concentration	About 0.05% to 12.5% by weight
Drug particle size	Major portion below about 155 micrometers
Microcrystalline cellulose	About 10% to 90%
Dibasic calcium phosphate	About 10% to 90%
Dibasic calcium phosphate form	Unmilled or coarse milled
Lubricant	About 0.1% to 3.0%
Starch	About 1% to 20%
Dosage form	Rapid-dissolving pharmaceutical composition

The invention is not limited to a particular active ingredient in claim 1. It is a formulation claim directed to the interaction among drug particle size, excipient selection, and tablet manufacture.

The principal technical distinction is the use of relatively fine drug particles with microcrystalline cellulose and coarse or unmilled dibasic calcium phosphate. The claims do not require wet granulation, a particular dissolution apparatus, a specified dissolution time, or a named commercial product.

How broad is claim 1 of US 4,517,179?

Claim 1 is broad in drug identity but narrow in formulation architecture. A competing product would generally need to satisfy each limitation to fall within its literal scope.

The claim has four principal boundaries:

The active ingredient must be a low-solubility drug.
The active ingredient must fall within the stated particle-size distribution.
The formulation must contain both microcrystalline cellulose and unmilled or coarse-milled dibasic calcium phosphate in the claimed ranges.
The formulation must contain starch and lubricant within the stated ranges.

The claim uses approximate language, including “about,” “major portion,” “low solubility,” and “coarse milled.” Those terms could create claim-construction disputes in an active case. The patent’s expiration eliminates the present infringement consequence, but the terms remain relevant to historical freedom-to-operate reviews, validity analysis, and patent-family interpretation.

Particle-size limitation

The particle-size limitation is central to the patent. Claim 1 requires that the major portion by weight of the drug particles be below approximately 155 micrometers. Claim 13 narrows that threshold to approximately 100 micrometers.

Claim 4 adds a more specific distribution requiring 84% by weight of the drug particles to be below approximately 100 micrometers. This is materially narrower than the general “major portion” limitation.

The patent therefore creates a hierarchy:

Claim	Particle-size limitation
Claim 1	Major portion below approximately 155 µm
Claim 4	84% below approximately 100 µm
Claim 13	Major portion below approximately 100 µm

Particle-size testing methodology would have been important in any infringement dispute. Results could vary depending on sieve analysis, laser diffraction, sampling, agglomeration control, and whether the measurement was performed on the active ingredient before blending or recovered from the finished dosage form.

Excipient limitations

Microcrystalline cellulose and dibasic calcium phosphate are both mandatory components in the independent composition claim. A formulation that substituted lactose, mannitol, dibasic calcium phosphate dihydrate with materially different particle properties, or another direct-compression filler could avoid literal infringement if the substitution removed a required limitation.

Claim 5 narrows the excipient proportions:

Microcrystalline cellulose: approximately 40% to 50%
Dibasic calcium phosphate: approximately 35% to 50%

Claim 8 narrows the dibasic calcium phosphate particle distribution by requiring that 50% by weight of the calcium phosphate particles have a diameter below approximately 100 micrometers.

The formulation claims are therefore sensitive to both chemical identity and physical grade. A supplier’s designation of “coarse,” “milled,” or “unmilled” would not alone determine infringement. Particle-size data and manufacturing records would be relevant.

What do the dependent claims cover?

Claim	Subject matter	Scope effect
2	Metolazone composition	Narrows claim 1 to metolazone
3	Fatty acid or fatty acid salt lubricant	Narrows the lubricant limitation
4	84% of drug particles below approximately 100 µm	Adds a specific distribution
5	40%-50% cellulose and 35%-50% calcium phosphate	Narrows excipient proportions
6	0.25-50 mg drug per tablet	Adds tablet drug-load limitation
7	0.25-2.5 mg metolazone per tablet	Narrow metolazone dosage range
8	50% of calcium phosphate particles below approximately 100 µm	Adds excipient particle-size limitation
10	Fine milling before mixing	Narrows the process
11	Compressed tablet	Narrows claim 1 to tablets
12	Triamterene composition	Narrows claim 1 to triamterene
13	Major portion of drug particles below approximately 100 µm	Narrows active particle size
14	Water solubility of approximately 1 part or less in 100 parts water at 25°C	Defines low-solubility drug class

Claims 2 and 12 are commercially important because they identify metolazone and triamterene, but neither claim protects the active ingredient itself. The claims cover only a particular dosage-form implementation.

What process does US 4,517,179 protect?

Claim 9 protects a process with four required stages:

Mix the low-solubility drug with microcrystalline cellulose, starch, unmilled or coarse-milled dibasic calcium phosphate, and lubricant.
Produce a uniform, free-flowing dry mixture.
Maintain the claimed concentration ranges and particle-size limitation.
Compress the mixture into tablets or fill it into capsules.

Claim 10 adds fine milling of the drug before mixing.

The process claims are narrower than a general claim to manufacturing a metolazone tablet. They require the specified dry blend, excipient system, particle-size characteristics, and dosage-form operation. A wet-granulation process, spray-drying process, hot-melt process, liquid-filled capsule, or formulation using a different filler system would not necessarily satisfy the process limitations.

Claim 9 also raises proof issues. “Uniform” and “free flowing” are functional or qualitative descriptions. A historical infringement analysis would likely require batch records, blend-uniformity data, flow testing, particle-size records, and manufacturing instructions.

When did US Patent 4,517,179 lose exclusivity?

US 4,517,179 issued on May 14, 1985. Under the pre-Uruguay Round patent-term regime, the ordinary term was 17 years from issue. The resulting nominal expiration date was May 14, 2002.[1]

Event	Date
Patent issued	May 14, 1985
Ordinary pre-URAA term	17 years from issue
Nominal expiration	May 14, 2002
Current enforceability	Expired

The patent is not an active exclusivity barrier in 2025. Any analysis of a current generic product should focus on later patents, regulatory exclusivity, manufacturing patents, formulation improvements, or patents covering a specific commercial product.

No patent-term extension under 35 U.S.C. § 156 should be inferred from the patent number or the claims alone. The patent is also too old to function as a current Orange Book patent listing for ordinary regulatory-exclusivity purposes.

What is the Orange Book status of US 4,517,179?

US 4,517,179 should not be treated as a current Orange Book barrier. The Orange Book lists patents submitted by an approved NDA holder that claim the drug substance, drug product, or an approved method of use.[2] This patent is a formulation patent for an older solid oral dosage platform and expired in 2002.

An Orange Book review for metolazone or triamterene should be conducted separately from the patent-number review. The relevant question is whether a current NDA holder has listed later patents against a particular approved product. US 4,517,179 itself does not create a current Paragraph IV filing obstacle.

Were Paragraph IV challenges or generic litigation associated with this patent?

A Paragraph IV certification is relevant only while a listed patent remains in force or otherwise creates a regulatory filing issue. Because US 4,517,179 expired in 2002, it cannot presently support a new Paragraph IV challenge as an unexpired Orange Book patent.

The supplied information does not establish a specific infringement action, ANDA litigation, or settlement agreement involving this patent. The claim set alone cannot prove that a particular generic manufacturer practiced the claimed formulation or that a particular litigation outcome occurred.

For current metolazone or triamterene products, litigation risk should instead be assessed against later patents covering:

Modified-release products
Combination products
New dosing regimens
Crystalline or polymorphic forms
Manufacturing processes
Stability-enhancing formulations
Drug-device systems
Specific indications or patient populations

What drugs and products are most closely connected to the patent?

Metolazone

Metolazone is a thiazide-like diuretic with low aqueous solubility. Claim 2 covers metolazone compositions meeting the claim 1 formulation requirements. Claim 7 narrows the formulation to 0.25 mg to 2.5 mg of metolazone per tablet.

The claimed dosage range overlaps conventional low-dose metolazone products. That overlap does not mean that every metolazone tablet infringed the patent. The product would also need to meet the excipient, lubricant, starch, and particle-size limitations.

Triamterene

Claim 12 identifies triamterene as another covered drug. Triamterene is a potassium-sparing diuretic with poor aqueous solubility. The claim is directed to a triamterene formulation using the specified excipient architecture, not to triamterene products generally.

Other low-solubility drugs

Claim 1 and claim 14 extend beyond metolazone and triamterene. Claim 14 provides a solubility-based limitation of approximately one part by weight or less in 100 parts by weight of water at 25°C.

The broad drug class could include multiple low-solubility compounds, but the formulation must still satisfy the quantitative excipient and particle-size requirements. A drug with low solubility but a different dosage-form system would not necessarily fall within the claims.

How strong was the patent estate?

The estate was technically meaningful but structurally concentrated. Its principal strength came from the combination of:

Low-solubility drug selection
Active particle-size reduction
Direct-compression excipients
Coarse or unmilled dibasic calcium phosphate
Starch
Lubricant
Rapid dissolution objective

Its principal limitations were equally clear:

No protection for the active pharmaceutical ingredient
No protection for every metolazone or triamterene dosage form
Dependence on measurable excipient and particle-size ranges
Potential design-around through alternative fillers, granulation methods, lubricants, or particle-size distributions
Expiration in 2002

The patent would have been more difficult to design around for a low-dose, direct-compression product using the same excipient system. It would have been easier to avoid through a materially different formulation platform.

What geographic coverage did the patent provide?

US 4,517,179 provided United States rights only. It did not create protection in Europe, Japan, Canada, or other jurisdictions unless corresponding foreign applications matured into separate patents.

A multinational product review therefore requires a family-level search. Patent expiration, prosecution history, claim scope, and litigation status could differ by country. The US expiration date cannot be transferred automatically to foreign counterparts.

What generic launch risks exist today?

For the specific patent, current generic launch risk is effectively zero because the patent expired more than two decades ago. A modern generic manufacturer could use the disclosed formulation concepts without infringing US 4,517,179.

The remaining commercial risks would arise from later rights, including:

Risk category	Relevance
Active-ingredient patents	Generally unlikely for old metolazone or triamterene products
Formulation patents	Possible for modified release, stability, or combination products
Method-of-use patents	Possible for new indications or dosing regimens
Manufacturing patents	Possible for later processes
Regulatory exclusivity	Must be checked against the current NDA
Trade secrets	Manufacturing know-how may remain protected
Product liability and quality	Independent of patent expiration

The patent does not create a biosimilar issue. Metolazone and triamterene are small-molecule drugs, so the relevant competitive pathway is an ANDA or, in some circumstances, a 505(b)(2) application rather than a biosimilar application under the Public Health Service Act.

Key Takeaways

US 4,517,179 covers rapidly dissolving compositions for low-solubility drugs.
The core formulation requires finely sized drug particles, microcrystalline cellulose, dibasic calcium phosphate, starch, and lubricant.
Metolazone and triamterene are expressly claimed embodiments.
The patent includes both composition and dry-blending process claims.
Particle size and excipient grade are major claim limitations.
The patent issued May 14, 1985, and its ordinary term expired May 14, 2002.
It is not a current US exclusivity barrier, Orange Book obstacle, or Paragraph IV litigation target.
Current product risk depends on later patents, regulatory exclusivity, and manufacturing rights.
The patent has no biosimilar relevance because the covered drugs are small molecules.

FAQs About US Patent 4,517,179

Does US 4,517,179 cover all metolazone tablets?

No. It covers metolazone tablets only when the formulation satisfies the specified drug particle-size, excipient, lubricant, starch, and concentration limitations.

Can a generic manufacturer use the formulation disclosed in US 4,517,179?

Yes, in the United States, because the patent’s ordinary term expired in 2002. Later patents covering a specific product or improvement would require separate review.

Does the patent protect metolazone as an active ingredient?

No. The patent protects a dosage-form composition containing metolazone, not metolazone itself.

Is US 4,517,179 relevant to a 505(b)(2) application?

Only as historical prior art and technical disclosure. It does not provide current exclusivity. A 505(b)(2) applicant would need to assess later patents and applicable FDA regulatory exclusivities.

What is the main design-around strategy for the claimed formulation?

The most direct approaches would involve changing the excipient system, using a different manufacturing process, altering the active particle-size distribution, or replacing dibasic calcium phosphate with another filler. Because the patent is expired, these strategies are no longer necessary to avoid infringement of this patent.

References

United States Patent and Trademark Office. (1985). U.S. Patent No. 4,517,179.
U.S. Food and Drug Administration. (2024). Approved Drug Products with Therapeutic Equivalence Evaluations: The Orange Book.
35 U.S.C. §§ 154, 156, 271, 282.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	53294	⤷ Start Trial
Australia	2643484	⤷ Start Trial
Australia	565640	⤷ Start Trial
Canada	1216236	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,517,179

Summary for Patent: 4,517,179