United States Patent 4,873,080: Scope, Claims, Expiration, and Repaglinide Patent Landscape

U.S. Patent 4,873,080 is an expired formulation and manufacturing patent directed to oral antidiabetic compositions containing an antidiabetic benzoic acid, principally repaglinide. Its core protection is not the repaglinide molecule itself. The patent requires a specific solid-dispersion or surface-deposition process using an acid-base excipient system, a solubilizer or emulsifier, and a water-insoluble carrier.

The patent issued October 10, 1989, and its 17-year term expired October 10, 2006. It therefore does not create a current U.S. barrier to generic repaglinide, repaglinide tablets, or manufacturing processes that would otherwise fall within the expired claims. The patent remains relevant as prior art and as an example of the formulation strategy used to improve dissolution of poorly soluble benzoic-acid antidiabetic compounds.

What does U.S. Patent 4,873,080 cover?

The patent covers two related subject matter groups:

A method of manufacturing an oral antidiabetic composition.
The resulting composition, including a method of treating diabetes with that composition.

The claims require the following technical sequence:

An antidiabetic benzoic acid is selected.
The active ingredient is combined with an acid or base, depending on whether the active compound is acidic, amphoteric, or basic.
The ingredients are dissolved or emulsified in an inert polar solvent.
At least one solubilizing or emulsifying substance is included.
The resulting solution or emulsion is applied to a water-insoluble carrier.
The treated carrier is dried.
The dried material may be combined with conventional pharmaceutical excipients.

The patent’s technical objective was to improve dispersion and oral performance of a poorly water-soluble antidiabetic benzoic acid. The claims do not cover every formulation containing repaglinide or every process that improves dissolution. They require the specified combination of chemical classes, ratios, carrier characteristics, and drying steps.

What compound is identified in claims 3 and 10?

Claims 3 and 10 identify the antidiabetic benzoic acid as:

2-Ethoxy-4-[2-oxo-2-[(α-isobutyl-2-piperidino-benzyl)-amino]-ethyl]benzoic acid.

This compound corresponds to the repaglinide active pharmaceutical ingredient, although modern chemical nomenclature commonly describes repaglinide as:

(S)-(+)-2-ethoxy-4-[2-[[3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]amino]-2-oxoethyl]benzoic acid.

Repaglinide is a short-acting insulin secretagogue in the meglitinide class. The U.S. Food and Drug Administration approved Prandin, the original repaglinide product marketed by Novo Nordisk, in 1997. The FDA label identifies repaglinide as an oral blood-glucose-lowering agent used in patients with type 2 diabetes [2].

The specific chemical limitations in claims 3 and 10 narrow those claims to compositions using repaglinide rather than the full universe of antidiabetic benzoic acids.

How broad is independent method claim 1?

Claim 1 is the principal process claim. It is broad in its use of functional categories but narrow in its required process architecture.

Required claim elements

A process likely must satisfy all of the following elements:

Claim element	Required limitation
Active ingredient	Acid, amphoteric, or basic antidiabetic benzoic acid
Acid-base component	Basic excipient for an acid active; basic or acid excipient for an amphoteric active; acid excipient for a basic active
Solvent	Inert polar solvent
Processing medium	Solution or emulsion
Solubilizer	At least one solubilizing or emulsifying substance
Carrier	Water-insoluble carrier
Application step	Solution or emulsion applied to the carrier surface
Drying step	Treated carrier dried
Active-to-excipient ratio	Molar ratio less than 1:1
Active-to-solubilizer ratio	About 1:0.5 to 1:10 by weight
Active-to-carrier ratio	1:1 to 1:12 by weight

The process does not merely require blending the active ingredient with excipients. The solution or emulsion must be applied to the surface of the water-insoluble carrier and then dried. A conventional wet granulation or direct-compression process would not necessarily meet the claim.

Scope of the acid-base limitation

For an acidic antidiabetic benzoic acid such as repaglinide, claim 1 requires a basic excipient. For an amphoteric antidiabetic benzoic acid, either a basic or acid excipient may be used. For a basic antidiabetic benzoic acid, an acid excipient is required.

This limitation is important because a formulation using repaglinide without a basic excipient would not satisfy the acid-active branch of claim 1. The claim also requires a molar ratio of benzoic acid to basic or acid excipient of less than 1:1. Claim 5 narrows that ratio to 1:1.8 through 1:10.

What formulations are protected by claims 6, 7, and 13?

Claims 6, 7, and 13 define specific carrier and solubilizer classes.

Water-insoluble carriers

The listed carriers include:

Highly dispersed silicon dioxide
Microcrystalline cellulose
Basic aluminum oxide
Magnesium-aluminum-trisilicate
Cross-linked polyvinylpyrrolidone
Sodium carboxymethyl starch
Tricalcium phosphate
Calcium biphosphate
Mixtures of those materials

These carriers provide a solid substrate for the dried residue. The claim does not require a single carrier. Mixtures are expressly included.

Solubilizing and emulsifying substances

The listed substances include:

Polyvinylpyrrolidone
Polyethylene glycol
Polyethoxylated sorbitan monooleate
Sorbitol
Polyoxyethylene polyoxypropylene polymer
Polyoxyethylene fatty alcohol ether
Glycerol polyethylene glycoloxy stearate
Mixtures of those materials

Claim 7 narrows the solubilizer to polyvinylpyrrolidone, a polyoxyethylene polyoxypropylene polymer, or a mixture of the two.

Claim 13 is a composition claim that combines the excipient, carrier, and solubilizer limitations. It is narrower than claim 9 because it requires specified classes of acid or base, carrier, and solubilizer.

How do claims 1 and 9 differ?

Claim 1 is a method claim. It requires the performance of the formulation process.

Claim 9 is a product or composition claim. It covers an oral antidiabetic composition consisting essentially of:

A conventional pharmaceutical excipient; and
A dry water-insoluble carrier bearing the evaporation residue of a solution or emulsion containing the active compound, acid or base, and solubilizer.

The phrase “consisting essentially of” generally permits additional ingredients that do not materially affect the basic and novel characteristics of the claimed composition. It is narrower than “comprising” but broader than “consisting of.”

The central product limitation is the “evaporation residue” on the water-insoluble carrier. A tablet that contains repaglinide and microcrystalline cellulose, but does not contain the claimed dried residue produced from the specified solution or emulsion, would present a weaker infringement case under claim 9.

What does claim 14 add?

Claim 14 covers a treatment method involving oral administration of a composition falling within claim 9 to a warm-blooded host requiring diabetes treatment.

The claim is dependent on the composition limitations. It does not independently cover oral administration of repaglinide in any formulation. An accused treatment would first need to involve a composition meeting claim 9.

Because claim 14 depends on the expired composition claim, it creates no current U.S. exclusivity. Its practical value was historically tied to the composition claims and the ability to assert method-of-treatment infringement against a product using the claimed formulation.

What is the expiration date of U.S. Patent 4,873,080?

Event	Date or status
U.S. patent	4,873,080
Publication and issue	October 10, 1989
Applicable U.S. term	17 years from issue for this pre-1995 patent
Expiration	October 10, 2006
Current status	Expired
Patent term extension	No current extension affecting the patent’s expiration

U.S. patents issued before June 8, 1995 generally received a term of 17 years from issue rather than 20 years from the earliest effective U.S. filing date. The Uruguay Round Agreements Act changed the term structure for later patents, but did not generally convert earlier patents to the modern 20-year term [3].

Patent 4,873,080 therefore expired before the first generic repaglinide approvals. Any current commercial analysis should treat the patent as historical prior art rather than as a live enforceable right.

What was the relationship between this patent and Prandin?

Prandin contains repaglinide and was approved by the FDA in December 1997. The product was developed and commercialized by Novo Nordisk. Patent 4,873,080 predates FDA approval and reflects an earlier formulation approach involving solubilization, acid-base adjustment, and deposition on an insoluble carrier.

The patent did not provide the primary long-term U.S. protection for the repaglinide molecule. That protection came from later compound, formulation, and use patents associated with repaglinide and Prandin. The later patent estate delayed generic entry after the expiration of U.S. Patent 4,873,080.

What patents protected repaglinide and Prandin?

The principal U.S. patent landscape included several later patents directed to repaglinide and its pharmaceutical use. Public FDA Orange Book records historically identified patents associated with Prandin, including the following:

Patent	General subject matter	Historical relevance
U.S. 5,216,167	Repaglinide-related compound and pharmaceutical subject matter	Later protection for the active ingredient
U.S. 5,312,924	Repaglinide-related pharmaceutical compositions or use	Extended product protection
U.S. 5,463,046	Additional repaglinide-related protection	Later-expiring patent estate
U.S. 6,143,769	Repaglinide use or formulation-related protection	Later Orange Book-listed protection

The precise scope of each later patent must be determined from its issued claims and applicable certificates, disclaimers, and patent-term calculations. They should not be conflated with U.S. 4,873,080, which is primarily a manufacturing and formulation-process patent.

The FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, known as the Orange Book, historically recorded patent information submitted for Prandin. Orange Book listing is a regulatory notice mechanism. It does not itself establish patent validity or infringement [1].

When did generic repaglinide enter the U.S. market?

Generic repaglinide entered the U.S. market after the expiration or resolution of later Prandin-related patent barriers, not after the 2006 expiration of U.S. Patent 4,873,080 alone.

The generic pathway was an Abbreviated New Drug Application under section 505(j) of the Federal Food, Drug, and Cosmetic Act. An ANDA applicant could certify under Paragraph IV that listed patents were invalid, unenforceable, or would not be infringed. A Paragraph IV filing could trigger patent litigation and a 30-month stay of approval under the Hatch-Waxman framework [4].

The commercial consequences were:

Patent 4,873,080 could not support a current Paragraph IV challenge because it had already expired.
Later listed patents associated with Prandin created the principal Paragraph IV risk.
Generic launch depended on the status of those later patents, any litigation, settlement terms, and FDA approval timing.
The expired 4,873,080 patent could still be cited as prior art against later formulation patents.

Were there Paragraph IV challenges to repaglinide patents?

Generic applicants seeking approval for repaglinide had an incentive to challenge later Orange Book-listed patents, particularly patents covering the active ingredient, formulations, or methods of use.

A Paragraph IV certification against an expired patent would have no practical litigation value. A challenge to a still-listed, unexpired patent could lead to:

A patent-infringement action by the brand sponsor;
A 30-month FDA approval stay;
An exclusivity period for the first eligible Paragraph IV filer;
Settlement or licensed-entry arrangements;
An authorized-generic strategy.

The relevant litigation risk therefore centered on later Prandin patents rather than U.S. 4,873,080. Once those later barriers expired or became unenforceable, repaglinide became an ordinary generic oral solid-dose product opportunity.

What is the Orange Book status of U.S. Patent 4,873,080?

U.S. Patent 4,873,080 is not a current source of Orange Book exclusivity. Its expiration predates current generic repaglinide competition.

The patent’s subject matter also illustrates an Orange Book issue: not every manufacturing patent is listed for an approved drug. FDA listing generally focuses on patents claiming the drug substance, drug product, or an approved method of use. A process patent may be ineligible for listing if it does not claim the approved product or approved use in the manner required by FDA regulations [1].

Accordingly, the patent should be analyzed separately from the Orange Book patents that historically delayed generic Prandin entry.

How strong was the patent estate?

The strength of U.S. Patent 4,873,080 was moderate for a narrowly defined formulation process and weak for broad repaglinide exclusivity.

Strengths

It combined chemical, formulation, carrier, and process limitations.
The claims identified specific excipient classes and quantitative ratios.
Claim 9 could reach the finished composition rather than only the manufacturing act.
Claim 14 provided a method-of-treatment claim tied to the claimed composition.

Weaknesses

The patent did not broadly claim repaglinide as a molecule.
The carrier and residue limitations created substantial design-around opportunities.
A competitor could potentially use a different solubilization system, carrier, drying process, or formulation architecture.
The patent expired in 2006.
The ratio limitations could create factual disputes involving analytical reconstruction of the finished product.

For modern freedom-to-operate analysis, the patent has no blocking strength in the United States. Its principal residual value is evidentiary: it may be cited against later patents claiming similar repaglinide solid dispersions, excipient combinations, or surface-deposition processes.

What generic entry risks existed?

Before expiration, a generic manufacturer would have faced several possible risks:

The product could have contained a dried active-excipient residue on a listed carrier.
The formulation might have used a basic excipient in the claimed molar range.
The manufacturing process could have applied a solution or emulsion to an insoluble carrier.
The finished dosage form might have met claim 9 even if the manufacturer used a different tableting process.
The brand owner could have argued that the generic product was materially equivalent to the patented composition.

Design-around options included:

Direct blending rather than surface deposition;
A non-listed carrier;
A different solvent system;
A different solubilizer;
A formulation without the claimed acid-base ratio;
A liquid, multiparticulate, or alternative solid-dosage architecture.

Those risks became legally immaterial in the United States after October 10, 2006.

Did the patent create biosimilar risk?

No. Repaglinide is a chemically synthesized small molecule, not a biologic. Biosimilar provisions under the Public Health Service Act do not apply. Generic repaglinide is approved through the ANDA pathway, subject to pharmaceutical equivalence, bioequivalence, labeling, manufacturing, and quality requirements.

The relevant competitors are generic drug manufacturers, not biosimilar sponsors.

What geographic coverage did the patent provide?

U.S. Patent 4,873,080 provided rights only in the United States. Corresponding foreign applications or patents would require separate analysis by country, including:

Filing and priority dates;
National-phase or convention status;
Local patent-term rules;
Supplementary protection certificates;
Translation requirements;
Local litigation and opposition records;
Product and process claim scope.

The U.S. expiration date cannot be applied automatically to Germany, the European Patent Convention states, Japan, Canada, or other jurisdictions. Any foreign counterpart could have had a different term or legal status.

Key Takeaways

U.S. Patent 4,873,080 covers a formulation process and composition for antidiabetic benzoic acids, principally repaglinide.
Its central technology is deposition of a solubilized or emulsified active-excipient system onto a water-insoluble carrier, followed by drying.
Claims 1 and 9 are the principal independent claims.
Claims 3 and 10 specifically identify repaglinide.
The claims require defined acid-base relationships, solubilizer-to-active ratios, carrier-to-active ratios, and drying architecture.
The patent expired October 10, 2006.
It does not currently block generic repaglinide in the United States.
Later patents, including U.S. 5,216,167, U.S. 5,312,924, U.S. 5,463,046, and U.S. 6,143,769, were more important to the commercial exclusivity period for Prandin.
Repaglinide is a small molecule, so biosimilar law is irrelevant.
The patent remains relevant as prior art and for historical analysis of repaglinide formulation technology.

FAQs

Does U.S. Patent 4,873,080 claim repaglinide itself?

No. Claims 3 and 10 identify repaglinide, but the independent claims require a particular formulation or manufacturing structure. The patent does not broadly claim all repaglinide compounds, formulations, or uses.

Can a generic repaglinide manufacturer use microcrystalline cellulose?

Yes, expiration of the patent removed the U.S. infringement risk from this patent. Before expiration, use of microcrystalline cellulose could have been relevant if combined with the other claimed residue, ratio, solubilizer, and drying limitations.

Is the patent relevant to current Prandin litigation?

Not as an enforceable U.S. patent. Any current litigation analysis would focus on later patents, regulatory exclusivity, trademarks, product liability, or other intellectual-property rights.

Does the patent cover a conventional repaglinide tablet?

Only if the tablet contains the claimed dry carrier bearing the specified evaporation residue and satisfies the composition limitations. A conventional tablet containing repaglinide and ordinary excipients is not automatically within claim 9.

Was a Paragraph IV certification required against this patent?

No current Paragraph IV certification is required against an expired patent. Historical ANDA applicants would have focused on unexpired Orange Book-listed Prandin patents, not on U.S. 4,873,080 after its 2006 expiration.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (1997). Prandin (repaglinide) prescribing information. FDA.
United States Patent and Trademark Office. (2024). Patent term calculator and patent term adjustment guidance. USPTO.
U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. FDA.
U.S. Patent No. 4,873,080. (1989). Antidiabetic pharmaceutical compositions and methods for their preparation. United States Patent and Trademark Office.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3320583	Jun 08, 1983

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	49886	⤷ Start Trial
Australia	2924184	⤷ Start Trial
Australia	562803	⤷ Start Trial
Canada	1228300	⤷ Start Trial
German Democratic Republic	223360	⤷ Start Trial
Germany	3320583	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,873,080

Summary for Patent: 4,873,080