United States Drug Patent 6,677,358: Scope, Claims, Expiration, and Patent Landscape for Repaglinide/Metformin

U.S. Patent No. 6,677,358 covers pharmaceutical combinations of repaglinide and metformin, including combined compositions, tablets, capsules, therapeutic administration, and kits containing separately formulated products. The patent was assigned to Novo Nordisk A/S and supported the combination product PrandiMet. Its core U.S. patent term expired on January 28, 2021, eliminating current U.S. patent-based blocking rights under the patent.[1][2]

What does U.S. Patent 6,677,358 protect?

The patent protects the use of repaglinide and metformin in combination for treating non-insulin-dependent diabetes mellitus, now generally called type 2 diabetes. Its five claims divide into three categories:

Claim	Subject matter	Scope
1	Pharmaceutical composition	Repaglinide and metformin with a suitable carrier
2	Tablet	Tablet form of the composition in claim 1
3	Capsule	Capsule form of the composition in claim 1
4	Method of treatment	Administering repaglinide with metformin to a patient with NIDDM
5	Kit	Repaglinide and metformin formulated for administration to the patient

Claim 1 is the principal composition claim. Claims 2 and 3 narrow claim 1 by specifying the dosage form. Claim 4 protects combination treatment even where repaglinide and metformin are not incorporated into the same tablet or capsule. Claim 5 covers a kit containing separately formulated quantities of the two active ingredients.

The claims do not expressly require:

A particular repaglinide dose.
A particular metformin dose.
A specific repaglinide-to-metformin ratio.
Immediate-release or extended-release delivery.
A particular salt of metformin beyond the claim language and specification context.
A particular dosing schedule.
A particular patient age, disease stage, or glycemic threshold.
A fixed-dose combination in every claim.
A particular carrier, excipient, coating, or manufacturing process.

The broadest commercial significance lies in the combination concept rather than in a narrow formulation feature.

How should claim 1 be construed?

Claim 1 recites a pharmaceutical composition "comprising repaglinide and metformin together with a suitable carrier."

The term "comprising" is open-ended. A composition containing repaglinide, metformin, and additional active or inactive ingredients can fall within the claim if the required elements are present. The claim therefore is not limited to a two-ingredient formulation.

"Together with a suitable carrier" requires a pharmaceutical composition rather than a mere mixture of raw chemicals. The carrier may include conventional excipients used to manufacture oral dosage forms. The claim does not identify a particular excipient or require a specific physical arrangement of the two drugs.

The main infringement question under claim 1 would have been whether a product contained both active ingredients in the same pharmaceutical composition. A package containing two separate products would raise a different issue because claim 5 expressly addresses a kit with separately formulated repaglinide and metformin.

Does claim 1 require a fixed-dose combination tablet?

No. Claim 1 requires a composition containing repaglinide and metformin, but it does not expressly require a tablet or a single unit-dose product. Claim 2 specifically recites a tablet, while claim 3 recites a capsule. This claim structure indicates that claim 1 is broader than either dosage-form claim.

A product with the two ingredients in a single tablet would implicate claim 1 and potentially claim 2. A capsule could implicate claims 1 and 3. A kit containing separately formulated products would be evaluated primarily under claim 5 and, depending on how the products are supplied and used, claim 4.

What do claims 2 and 3 protect?

Tablet protection under claim 2

Claim 2 depends on claim 1 and covers the repaglinide/metformin composition in tablet form. The claim does not require a particular tablet architecture, such as:

Bilayer construction.
Immediate-release and extended-release layers.
Film coating.
Specific hardness or dissolution profile.
A specific excipient system.
A defined dose of either ingredient.

A tablet containing both active ingredients would have been the clearest commercial target of claim 2. The claim is narrower than claim 1 because it requires a tablet, but it remains broad in the absence of formulation limitations.

Capsule protection under claim 3

Claim 3 covers the composition in capsule form. It does not appear limited to hard-shell capsules, soft-gel capsules, a particular fill material, or a specific release profile.

The capsule claim would have covered a conventional capsule containing both repaglinide and metformin, assuming the composition satisfied claim 1.

What does method claim 4 protect?

Claim 4 covers:

A method for treating NIDDM comprising administering to a patient in need of such treatment repaglinide in combination with metformin.

This is a broad method-of-use claim. It requires:

A patient with NIDDM.
Administration of repaglinide.
Administration of metformin.
Combination treatment.

The claim does not require the two drugs to be administered in one dosage form. Separate prescriptions, separate tablets, or different administration times could potentially satisfy the combination requirement if the drugs were administered as part of the same treatment regimen.

The claim also does not state a specific treatment sequence. It does not require repaglinide to be administered before metformin, or vice versa. It does not recite meal timing, titration, frequency, or treatment duration.

The claim's breadth is limited by its disease and combination-treatment elements. It does not cover repaglinide monotherapy, metformin monotherapy, or treatment of diseases other than NIDDM under its express language.

What does kit claim 5 protect?

Claim 5 covers a kit containing:

An amount of repaglinide formulated for administration.
An amount of metformin formulated for administration.

Unlike claim 1, claim 5 does not require both drugs to be in the same composition. It is directed to a packaged combination in which the products may be separately formulated.

The kit claim is commercially relevant to:

Co-packaged repaglinide and metformin products.
Patient starter packs.
Combination treatment packs.
Separate dosage forms sold together with treatment instructions.
Packaging that directs use of the two drugs in combination.

A kit containing unrelated quantities without combination-use instructions would present a weaker infringement case than a package expressly designed for concurrent treatment. The claim language, however, focuses on the contents and formulation rather than a detailed packaging design.

How many patents cover the repaglinide/metformin combination?

The principal U.S. patent specifically directed to the repaglinide/metformin combination was U.S. Patent 6,677,358. The broader repaglinide and metformin patent estates were separate from the combination patent.

Patent or regulatory right	Relevance	Status
U.S. Patent 6,677,358	Repaglinide/metformin compositions, treatment, and kits	Expired January 28, 2021
Earlier repaglinide compound patents	Repaglinide active ingredient and related uses	Expired before or around the launch period of combination products
Metformin patents	Metformin chemistry, formulations, and uses	Generally expired
FDA approval exclusivity	Regulatory protection for the approved product	Expired
Product-specific formulation patents	Potentially relevant only if separately listed or independently valid	Requires product and Orange Book review

The expired status of 6,677,358 does not mean every possible formulation or manufacturing process is free of patent risk. A later patent could theoretically cover a particular release profile, excipient combination, manufacturing process, or delivery system. The identified patent itself, however, no longer provides an enforceable U.S. exclusion right.

What was the Orange Book status of PrandiMet?

PrandiMet is the fixed-dose combination of repaglinide and metformin hydrochloride marketed by Novo Nordisk. The FDA approved PrandiMet under NDA 022195 in 2008.[3]

Historical Orange Book records identified U.S. Patent 6,677,358 in connection with the product. The patent supported the combination product rather than repaglinide or metformin as separate products.[2]

Regulatory item	Data
Product	PrandiMet
Active ingredients	Repaglinide and metformin hydrochloride
Sponsor	Novo Nordisk
NDA	022195
FDA approval	2008
Dosage forms	Oral tablets
Historical patent	U.S. 6,677,358
Patent expiration	January 28, 2021
Current patent blocking position	None under U.S. Patent 6,677,358

FDA Orange Book listing does not itself establish patent validity or infringement. It identifies patent information submitted by the NDA holder and can support regulatory notice obligations for an ANDA applicant.

When did repaglinide/metformin lose U.S. exclusivity?

The relevant patent exclusivity under U.S. Patent 6,677,358 ended on January 28, 2021. FDA regulatory exclusivity for the approved product also expired before the current period.

The commercial loss of exclusivity should be assessed separately from patent expiration:

Patent exclusivity: ended with expiration of U.S. Patent 6,677,358.
New chemical entity exclusivity: not available for PrandiMet because repaglinide and metformin were previously approved active ingredients.
Combination-product regulatory exclusivity: limited and expired.
Pediatric exclusivity: no extension is identified for the patent.
Formulation exclusivity: no continuing Orange Book barrier is identified from the patent itself.

After expiration, an ANDA applicant could rely on the approved product's safety and efficacy findings, subject to FDA requirements for pharmaceutical equivalence, bioequivalence, labeling, and manufacturing quality.

Were there Paragraph IV challenges or patent litigation?

The key Paragraph IV issue would have been an ANDA applicant's certification that U.S. Patent 6,677,358 was invalid, unenforceable, or not infringed. A Paragraph IV certification could trigger patent litigation under the Hatch-Waxman framework if the patent remained listed and the NDA holder sued within the statutory period.

The public significance of the patent was strongest before January 2021, when an ANDA applicant seeking approval for a repaglinide/metformin equivalent could have faced a patent-based delay or litigation risk. After expiration, the patent could no longer support a conventional infringement action against post-expiration commercial activity.

No continuing U.S. patent litigation risk arises from U.S. Patent 6,677,358 after its expiration date. Any historical Paragraph IV dispute would need to be analyzed based on the filing date, notice date, asserted claims, and settlement terms. The patent's expiration removes prospective injunctive relief under this patent.

What formulation patents protect repaglinide/metformin products?

U.S. Patent 6,677,358 does not depend on a sophisticated formulation platform. Its claims do not recite:

Controlled release.
Enteric release.
Bilayer tablets.
A defined dissolution window.
Particle-size limitations.
A particular excipient matrix.
A specific stability package.
A manufacturing sequence.

That makes the patent broader than a conventional formulation patent but also exposes it to validity attacks based on earlier disclosures of repaglinide/metformin coadministration or combination therapy.

A later entrant would still need to review patents covering:

Extended-release metformin.
Modified-release repaglinide.
Combination tablets with defined dissolution profiles.
Salt, polymorph, or particle-size claims.
Manufacturing processes.
Packaging and dosing regimens.
New methods for selected patient populations.

Those rights are distinct from the claims of 6,677,358 and cannot be inferred from the patent alone.

How strong was the patent estate for repaglinide/metformin?

The estate was commercially useful but structurally concentrated. Its strengths were:

Direct coverage of the two active ingredients in one composition.
Separate protection for tablets and capsules.
A method claim that did not require coformulation.
A kit claim covering separately formulated products.
Alignment with the commercial fixed-dose combination product.

Its limitations were:

No dose limitations.
No pharmacokinetic or clinical endpoint limitation.
No specific formulation technology.
No manufacturing-process protection.
No express protection for a unique release profile.
Dependence on a combination concept involving two already-known drugs.
Expiration in 2021.

From a validity perspective, the broad claims could have faced obviousness arguments if prior art taught repaglinide and metformin as complementary treatments for type 2 diabetes. The patent's practical value therefore came from its issuance, Orange Book listing, and market timing rather than from a dense, layered patent portfolio.

Which companies challenged or competed with PrandiMet?

Novo Nordisk was the principal branded sponsor associated with PrandiMet. Competition came from separate products rather than from a large branded repaglinide/metformin market:

Product category	Examples	Relationship to 6,677,358
Repaglinide monotherapy	Prandin and generic repaglinide	Does not contain metformin
Metformin monotherapy	Glucophage and generic metformin	Does not contain repaglinide
Other metformin combinations	Sulfonylurea, DPP-4, SGLT2, or thiazolidinedione combinations	Therapeutic substitutes, not direct claim targets
Repaglinide/metformin equivalents	Potential ANDA products after patent expiry	Direct post-expiration competition

The combination faced substantial therapeutic competition from newer type 2 diabetes products, including DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, and insulin products. Those products do not necessarily create patent infringement risk under 6,677,358 because they do not contain repaglinide and metformin together.

What generic launch risks existed?

Before January 28, 2021, the main generic launch risks were:

A Paragraph IV challenge could have triggered patent litigation.
A 30-month stay could have delayed approval if litigation was timely initiated.
A product using separate repaglinide and metformin dosage forms could still have raised method or kit claim issues.
A fixed-dose tablet could have implicated composition and tablet claims simultaneously.
A formulation with a different excipient system would not necessarily avoid claim 1 because the claim contains no excipient limitation.

After expiration, the patent-specific launch risks became limited to historical litigation, regulatory requirements, and any separate unexpired patents. The principal operational barriers shifted to bioequivalence, product development, manufacturing validation, supply economics, and market demand.

Did the patent create manufacturing or licensing barriers?

The patent did not claim a difficult manufacturing process. It covered the product concept and therapeutic combination rather than a specialized production method. A technically competent manufacturer could develop a tablet or capsule using conventional pharmaceutical processes, subject to formulation performance and regulatory requirements.

No public licensing arrangement is required to practice an expired U.S. patent. Historical commercialization was associated with Novo Nordisk, but expiration eliminates the need for a license under the patent in the United States. Separate rights in other jurisdictions must be assessed country by country.

What is the geographic coverage of U.S. Patent 6,677,358?

The patent provides rights only in the United States. Foreign counterparts, if granted, had separate terms, claim scopes, maintenance requirements, and expiration dates.

A global freedom-to-operate review should examine:

European Patent Office and national European validations.
Canada.
Japan.
Australia.
Brazil.
China.
India.
Countries where PrandiMet or equivalent products were marketed.

U.S. expiration does not establish worldwide freedom to operate. Conversely, a foreign patent expiration does not affect U.S. rights.

Key Takeaways

U.S. Patent 6,677,358 covers repaglinide/metformin compositions, tablets, capsules, combination treatment, and kits.
Claim 1 is the central composition claim and uses broad "comprising" language.
Claim 4 can cover separate administration of repaglinide and metformin, not only a fixed-dose tablet.
Claim 5 addresses co-packaged but separately formulated products.
The patent did not claim a specific dose, release profile, excipient system, or manufacturing process.
The patent supported Novo Nordisk's PrandiMet product and was historically relevant to Orange Book and ANDA strategy.
The patent expired on January 28, 2021.
No current U.S. exclusionary right remains under this patent.
Post-expiration competition depends on FDA approval, bioequivalence, manufacturing economics, and any separate later-issued patents.
Foreign patent rights require independent country-by-country review.

FAQs About U.S. Patent 6,677,358

Can a generic manufacturer sell repaglinide and metformin in separate bottles?

Yes, U.S. Patent 6,677,358 expired on January 28, 2021. Before expiration, separate-bottle sales could still have implicated the method or kit claims depending on product packaging, labeling, and intended combination use.

Does the patent cover repaglinide alone?

No. The asserted claims require repaglinide in combination with metformin. Repaglinide monotherapy is outside the express scope of these claims.

Does the patent cover all metformin combinations?

No. The claims require repaglinide and metformin. Combinations of metformin with other antidiabetic agents do not fall within these claims solely because they contain metformin.

Could an extended-release repaglinide/metformin product avoid the patent?

Before expiration, an extended-release product could still have fallen within claim 1 if it contained both active ingredients and a suitable carrier. The absence of an express release-profile limitation would not itself avoid the composition claim.

Is PrandiMet still protected by U.S. patent 6,677,358?

No. The patent expired on January 28, 2021. Any present patent analysis must focus on separate unexpired patents, regulatory requirements, trademarks, and non-U.S. rights.

References

United States Patent and Trademark Office. (2004). U.S. Patent No. 6,677,358, Pharmaceutical compositions comprising repaglinide and metformin. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
U.S. Food and Drug Administration. (2008). PrandiMet (repaglinide and metformin hydrochloride) prescribing information and approval records. FDA.
U.S. Food and Drug Administration. (n.d.). Electronic Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
United States Code, 35 U.S.C. § 154. Patent term.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Denmark	0694/97	Jun 13, 1997

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	201139	⤷ Start Trial
Australia	7906898	⤷ Start Trial
Germany	69800806	⤷ Start Trial
Denmark	1011673	⤷ Start Trial
European Patent Office	1011673	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,677,358

Summary for Patent: 6,677,358