US Patent 6,844,008: Mitiglinide Tablet Claims, Patent Scope, Expiration Risk, and Generic Landscape

US Patent 6,844,008 protects a specific oral tablet formulation containing N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine, the free-acid form of mitiglinide, together with one of three specified cellulose-based disintegrants. The patent is a formulation patent, not a broad compound patent. Its principal commercial relevance is therefore limited to tablets that use the claimed active ingredient and satisfy the listed excipient requirements.

The strongest enforceable scope is concentrated in claim 1 and its disintegrant-specific claims 4-6. The filler, active-ingredient concentration, binder, and hydroxypropylcellulose limitations narrow the protected formulation further. The patent does not, based on the supplied claims, broadly cover every mitiglinide product, every mitiglinide salt, injectable products, capsules, or formulations using an unlisted disintegrant.

What drug and formulation does US Patent 6,844,008 protect?

The claimed active ingredient is N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine, commonly associated with mitiglinide. Mitiglinide is a short-acting insulin secretagogue in the meglitinide class and is commercially associated with mitiglinide calcium hydrate products such as Glufast in Japan.

The patent focuses on a tablet designed to provide oral absorption that is not significantly influenced by meals. The core formulation requires:

Claim element	Requirement
Dosage form	Tablet
Active ingredient	N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine
Required excipient	Sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, or croscarmellose sodium
Optional filler	Lactose, starch, crystalline cellulose, calcium monohydrogen phosphate, light anhydrous silicic acid, titanium oxide, or magnesium aluminometasilicate
Active concentration	5% to 50% by weight under claim 10
Filler concentration	10% to 90% by weight under claim 8
Optional binder	A binder, including hydroxypropylcellulose
Hydroxypropylcellulose concentration	0.5% to 2% by weight under claim 13
Therapeutic use	Inhibiting a rise in blood sugar

The claims use “comprising,” which generally leaves the formulation open to additional ingredients unless those ingredients conflict with another claim limitation. A tablet containing the required active ingredient and one listed disintegrant can therefore fall within claim 1 even if it also contains lubricants, coatings, colorants, surfactants, or other excipients.

How broad is claim 1 of US Patent 6,844,008?

Claim 1 is the principal composition claim. It has two mandatory technical elements:

The tablet must contain the specified mitiglinide compound.
The tablet must contain at least one of three named disintegrants.

The disintegrant Markush group is:

Sodium carboxymethyl cellulose
Calcium carboxymethyl cellulose
Croscarmellose sodium

A tablet using a different disintegrant, such as crospovidone, sodium starch glycolate, or a formulation-specific polymer not covered by the list, would not literally satisfy the disintegrant limitation of claim 1. Infringement under the doctrine of equivalents would depend on the patent specification, prosecution history, and the technical interchangeability of the excipient.

Claim 1 does not require:

A particular tablet weight
A particular release profile
A particular compression force
A particular coating
A particular dosage strength
A particular salt form
A particular manufacturing process
A particular particle size
A particular dissolution specification

Those omissions increase the breadth of claim 1 within the defined active-ingredient and disintegrant combination.

What formulations are protected by claims 2 through 14?

The dependent claims create narrower formulation positions rather than materially expanding the patent.

Claim	Subject matter	Practical effect
2	Tablet with absorption not significantly influenced by meals	Adds a pharmacokinetic or performance limitation
4	Sodium carboxymethyl cellulose	Species claim to one listed disintegrant
5	Calcium carboxymethyl cellulose	Species claim to a second disintegrant
6	Croscarmellose sodium	Species claim to a third disintegrant
7	Listed fillers	Adds a closed filler group
8	Filler at 10%-90% by weight	Adds a quantitative formulation limitation
9	Lactose	Narrower filler embodiment
10	Active ingredient at 5%-50% by weight	Adds a quantitative active-content limitation
11	Binder	Adds a binder requirement
12	Hydroxypropylcellulose	Narrows the binder to HPC
13	HPC at 0.5%-2% by weight	Adds a quantitative HPC limitation
14	One or more listed additives	Broad additive-dependent claim, but still dependent on claim 1

Claim 14 is unusual because it lists “a disintegrator” even though claim 1 already requires a disintegrant. Its practical scope is therefore dependent on the interpretation of the additive list and does not remove the claim 1 requirement.

Does the patent cover mitiglinide calcium?

The commercial product is commonly described as mitiglinide calcium hydrate, while the supplied claims identify N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine without expressly reciting calcium or a hydrate.

That distinction matters. A claim directed to the free acid does not automatically cover a calcium salt. Literal infringement would depend on whether the claimed chemical identity encompasses the salt as used in the tablet. The analysis would turn on:

The patent’s specification and chemical definitions
Whether the claims use “comprising” to encompass a salt or salt-derived active
Prosecution statements distinguishing salts from the free acid
The physical form of the active ingredient in the accused tablet
Whether the product dissociates in the dosage form or gastrointestinal environment

A mitiglinide calcium tablet could present a non-infringement position if the claim is construed narrowly to require the free acid. That position would not be conclusive without reviewing the complete patent file history and product composition.

What method-of-use protection does the patent provide?

Claim 3 covers a method of inhibiting a rise in blood sugar by administering the tablet of claim 1. Claims 15-17 narrow that method to the three specific disintegrants.

The method claims do not appear to cover:

Administration of mitiglinide in a capsule
Administration of an injectable product
Administration of a tablet using an unlisted disintegrant
Use of a different active ingredient
A method that does not administer the claimed tablet

The phrase “inhibiting the rise of blood sugar” is broader than a specific diabetes diagnosis or a defined postprandial glucose endpoint. The claim nevertheless incorporates all limitations of claim 1. A party that administers a covered tablet could face direct method-infringement exposure. A manufacturer or distributor could face induced-infringement theories if the product labeling instructs the claimed use.

When does US Patent 6,844,008 lose exclusivity?

The issue date, January 18, 2005, does not by itself determine expiration. US utility patents filed after June 8, 1995 generally expire 20 years from the earliest effective US nonprovisional or international application filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and relevant prosecution events (35 U.S.C. § 154).

The supplied claims do not provide the priority date, US filing date, patent-term adjustment, or terminal-disclaimer information. The enforceability date must therefore be taken from the USPTO patent record rather than calculated from the issue date alone.

Exclusivity item	Assessment
Patent type	US formulation and method-of-use patent
Issue date	January 18, 2005
Statutory term	Generally 20 years from the applicable earliest US filing date
Patent-term extension	No extension is established by the supplied claim set
Patent-term adjustment	Must be checked in USPTO Patent Center
Current commercial risk	Likely term-expired or near-term-expired based on the early-2000s filing period, but the controlling expiration date is the USPTO record
FDA regulatory exclusivity	No US FDA mitiglinide approval or associated exclusivity is established by the supplied information

The patent was prosecuted under the pre-2011 patent-law framework, but its term is generally governed by the modern 20-year-from-filing rule rather than the former 17-year-from-issue rule.

What is the Orange Book status of mitiglinide?

Mitiglinide does not have an established US FDA reference-listed-drug position comparable to major US diabetes products such as repaglinide, nateglinide, sitagliptin, or insulin products. The absence of a US-approved mitiglinide product has several consequences:

There is no ordinary Orange Book listing for a US mitiglinide reference product established by the supplied record.
There is no conventional Orange Book patent-listing framework for this patent against a US mitiglinide RLD.
A Paragraph IV challenge generally requires an ANDA referencing an FDA-approved drug.
A US applicant would more likely evaluate a 505(b)(2) pathway or a different 505(j) strategy if an appropriate reference product became available.
FDA regulatory exclusivity cannot be inferred from the existence of US Patent 6,844,008.

An Orange Book absence does not make the patent irrelevant. Patent rights may be asserted independently of Orange Book listing, but the standard ANDA certification and automatic 30-month-stay mechanism are tied to the statutory ANDA framework.

Which companies are challenging US Patent 6,844,008?

No Paragraph IV challenger, ANDA litigation, or settlement agreement can be established from the claim text. Because mitiglinide lacks a clearly established US reference-listed product, the usual generic litigation pattern associated with an Orange Book-listed blockbuster drug is not apparent.

The principal commercial entities associated with mitiglinide development and marketing have historically included Kissei Pharmaceutical and regional partners or licensees. The commercial product has been concentrated outside the United States, particularly in Japan and selected Asian markets. The supplied materials do not establish a US licensing transaction, patent settlement, or active district-court case involving Patent 6,844,008.

How does this patent compare with an API or compound patent?

US Patent 6,844,008 is materially narrower than a compound patent.

Patent category	Typical protected subject matter	Relevance of US 6,844,008
Compound patent	The mitiglinide molecule and related compounds	Not established by the supplied claims
Salt or crystal-form patent	Calcium salt, hydrate, polymorph, or crystal form	Not expressly claimed
Formulation patent	Tablet composition and excipients	Primary subject of US 6,844,008
Method-of-use patent	Treatment or glucose-control use	Present in claims 3 and 15-17
Manufacturing patent	Granulation, compression, coating, or process parameters	Not expressly claimed
Drug-delivery patent	Modified release or targeted delivery system	Not expressly claimed

A competitor that avoids the claimed disintegrants may reduce risk under the literal wording of claim 1. A competitor using mitiglinide calcium rather than free-acid mitiglinide may also have a claim-construction defense, although the patent specification and prosecution history would control.

What generic launch risks exist?

The main launch risks are formulation-specific rather than molecule-wide.

Higher-risk formulation

A mitiglinide tablet is at higher risk if it:

Uses the claimed active ingredient
Contains croscarmellose sodium, sodium carboxymethyl cellulose, or calcium carboxymethyl cellulose
Falls within the claimed active or filler concentration ranges
Uses lactose and hydroxypropylcellulose in the claimed amounts
Makes meal-independent absorption or postprandial glucose-control claims

Lower-risk formulation

Risk is reduced where the product:

Uses a different disintegrant
Uses a different dosage form
Uses a distinct salt or solid-state form not covered by the claim construction
Omits the claimed active compound
Uses a formulation outside the dependent concentration ranges
Avoids labeling that instructs the patented method

A design-around based only on changing the disintegrant may not address other patent-family members. A complete freedom-to-operate review should examine compound, salt, polymorph, process, formulation, and use patents across the target countries.

What is the patent strength of US Patent 6,844,008?

The patent has moderate formulation specificity and limited molecule-wide coverage.

Its strengths are:

A clear tablet-plus-active-plus-disintegrant combination
Three expressly protected disintegrant species
Dependent claims covering common excipients and concentration ranges
Method claims tied to the formulation

Its limitations are:

No apparent broad compound claim
No express salt, hydrate, polymorph, or crystal-form claim
No express manufacturing-process claim
Potential construction issues concerning free acid versus calcium salt
Potential enablement and written-description scrutiny for the meal-effect limitation in claim 2
Dependence on proving the composition of an accused commercial tablet

The most important diligence issue is claim construction around the active ingredient and the calcium salt. The second is evidence of excipient identity and concentration in the accused product.

Key Takeaways

US Patent 6,844,008 is a mitiglinide tablet formulation patent.
Claim 1 requires the active ingredient and one of three specified cellulose-based disintegrants.
Claims 4-6 separately protect each listed disintegrant.
Claims 7-14 narrow the formulation through fillers, concentrations, lactose, binders, and hydroxypropylcellulose.
Claims 3 and 15-17 cover administration of the claimed tablet to inhibit blood-sugar elevation.
The patent does not, from the supplied claims, broadly cover mitiglinide compounds, calcium salts, capsules, injectables, or all oral formulations.
Mitiglinide calcium must be analyzed separately from the claimed free-acid chemical name.
No US Orange Book listing, Paragraph IV challenge, or settlement is established by the supplied record.
The controlling expiration date requires the USPTO priority, filing, patent-term-adjustment, and terminal-disclaimer data.
Generic risk is highest for a tablet that uses mitiglinide together with one of the three claimed disintegrants.

FAQs

Does US Patent 6,844,008 cover every mitiglinide tablet?

No. The claims require the specified mitiglinide compound and one of three listed disintegrants. A tablet using a different active form, dosage form, or disintegrant may fall outside the literal scope.

Is croscarmellose sodium the same as croscaramellose sodium in the claims?

“Croscaramellose sodium” appears to be a spelling error in the supplied claims. The recognized excipient name is “croscarmellose sodium.” Claim interpretation would rely on the issued patent and its intrinsic record.

Can a competitor avoid the patent by using crospovidone?

Potentially, if crospovidone is the only disintegrant and the claim is construed according to its express Markush group. Equivalence and other patent-family claims would still require separate analysis.

Does a patent expiration eliminate all US mitiglinide launch barriers?

No. Expiration of this formulation patent would not resolve regulatory approval, manufacturing, API, salt-form, polymorph, trademark, or other patent issues.

Is a Paragraph IV certification available against this patent?

Only if the applicant files an ANDA referencing an FDA-approved product and the patent is properly listed for that reference product. The absence of an established US mitiglinide reference-listed drug makes the ordinary Paragraph IV route uncertain.

References

United States Patent and Trademark Office. (2005). US Patent No. 6,844,008, pharmaceutical tablet containing N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine. U.S. Department of Commerce.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights. Office of the Law Revision Counsel.
United States Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
United States Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance. U.S. Department of Commerce.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	8-318541	Nov 15, 1996

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	322260	⤷ Start Trial
Austria	503472	⤷ Start Trial
Australia	4965497	⤷ Start Trial
Australia	718350	⤷ Start Trial
Canada	2271865	⤷ Start Trial
China	1242704	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,844,008

Summary for Patent: 6,844,008