United States Drug Patent 6,211,205: Claim Scope, Expiration, Litigation and Patent Landscape

US Patent 6,211,205 covers combination treatment of diabetes using a thiazolidinedione-class insulin-sensitizing compound with an insulin secretion enhancer. The patent’s commercially relevant embodiments are pioglitazone plus glibenclamide or another sulfonylurea. The patent issued on April 3, 2001 and its enforceable term ended in 2018. It does not currently create a blocking patent risk for generic pioglitazone, glibenclamide, or combination therapy.

What does US Patent 6,211,205 protect?

The patent claims a method of reducing the quantity of active ingredients administered to a diabetic patient by co-administering:

A compound within a broad chemical genus, or a pharmaceutically acceptable salt; and
An insulin secretion enhancer.

The commercial core is the combination of pioglitazone and a sulfonylurea, especially glibenclamide, also known as glyburide.

The patent is a method-of-treatment patent. It does not primarily claim:

A new chemical entity;
A specific tablet or dosage form;
A manufacturing process;
A fixed-dose pharmaceutical composition as such; or
A device or delivery system.

Infringement therefore depends on performance of the claimed treatment method, not merely possession or sale of the individual active ingredients.

Patent identification and term

Field	Information
U.S. patent	US 6,211,205
Patent type	Utility patent
Issue date	April 3, 2001
General subject	Diabetes treatment using an insulin sensitizer and insulin secretion enhancer
Principal assignee	Takeda Chemical Industries, Ltd.
Key commercial compound	Pioglitazone
Key combination	Pioglitazone plus glibenclamide or another sulfonylurea
Patent term	Ended in 2018
Current blocking effect	None, because the patent has expired

The term was governed by the 20-year patent-term rule applicable to the relevant U.S. filing or international application date. The patent’s effective term ended in 2018, absent an unusual term adjustment or extension. No current patent-term extension creates a remaining enforceable period for the claims described here. [1][2]

How broad is claim 1 of US 6,211,205?

Claim 1 is materially broader than the named pioglitazone embodiment. It uses a Markush definition for the active compound and separately defines a broad class of insulin secretion enhancers.

The claim requires the following elements:

Claim element	Scope
Patient	A diabetic patient
Therapeutic action	Administration of a therapeutically effective amount
First active component	A compound satisfying the stated structural formula or a pharmaceutically acceptable salt
Second active component	An insulin secretion enhancer
Claimed result	Reduction in the amount of the respective active components administered

The claim is narrower than a simple “two-drug combination” claim because the first compound must satisfy the specified structural formula. It is broader than a pioglitazone-only claim because it reaches a large genus of compounds.

Functional limitation: “reducing the amount”

The phrase requiring reduction in the amount of the respective active components is significant. It indicates that the invention is directed to combination therapy that permits lower quantities of the component drugs while maintaining therapeutic benefit or improving treatment performance.

A potential infringement analysis would examine:

Whether both agents are administered to the same diabetic patient;
Whether the first agent falls within the claimed structural formula;
Whether the second agent is an insulin secretion enhancer;
Whether the treatment regimen uses reduced quantities relative to monotherapy or prior treatment;
Whether the accused product labeling instructs the claimed method.

The claim does not expressly require a particular dose, dose ratio, treatment duration, blood-glucose endpoint, or formulation. That creates breadth, but it also creates potential validity and proof issues. A patent owner would need to establish that the accused regimen satisfies the claimed therapeutic method, including the reduction limitation.

Which compounds are covered by the patent?

Claims 2, 3, 6 and 7 identify narrower compound embodiments. Claim 3 expressly names pioglitazone. Claim 7 names troglitazone. Claim 6 identifies another thiazolidinedione-related compound, although the chemical name supplied in the question appears to contain transcription errors.

Commercially important compound coverage

Claim	Compound scope	Commercial relevance
Claim 1	Broad structural genus	Potentially covers multiple insulin-sensitizing compounds
Claim 2	Specific formula not reproduced in the supplied text	Exact scope cannot be assessed from the text provided
Claim 3	Pioglitazone and pharmaceutically acceptable salts	Principal Actos-related embodiment
Claim 6	Named pyridyl-substituted thiazolidinedione	Chemical identity requires comparison with the issued patent
Claim 7	Troglitazone and pharmaceutically acceptable salts	Historical Rezulin-related embodiment

Pioglitazone is the most commercially important compound in the claim set. Troglitazone was withdrawn from the U.S. market because of hepatotoxicity concerns and does not create a current commercial infringement issue.

The broad genus in claim 1 includes compounds defined through:

Heterocyclic or hydrocarbon substituents;
Carbonyl, hydroxyl-bearing or amino-linked groups;
Variable chain lengths;
Oxygen or sulfur atoms;
Substituted aromatic or heteroaromatic rings; and
Pharmaceutically acceptable salts.

The breadth is constrained by the precise atom connectivity in the formula. Chemical structures that have similar pharmacology but fall outside the defined scaffold would not infringe claim 1 merely because they improve insulin sensitivity.

What do claims 3, 4, 5, 8, 9 and 12 add?

The dependent claims progressively narrow the combination.

Pioglitazone claims

Claim 3 covers pioglitazone or a pharmaceutically acceptable salt in combination with an insulin secretion enhancer.

Claim 5 is the clearest commercial claim. It requires:

Pioglitazone; and
Glibenclamide.

A product or regimen using pioglitazone with glibenclamide would fall within the literal scope of claim 5 if the method requirements were met. Because the patent expired, that historical scope has no current exclusionary effect.

Sulfonylurea claims

Claim 8 defines the insulin secretion enhancer as a sulfonylurea. Claim 9 lists numerous specific sulfonylureas, including:

Tolbutamide;
Chlorpropamide;
Tolazamide;
Acetohexamide;
Glibenclamide or glyburide;
Gliclazide;
Glipizide;
Gliquidone;
Glimepiride; and
Several older compounds.

Claim 9 is a closed list of named compounds within the dependent-claim structure. A sulfonylurea not listed in claim 9 could still potentially fall under claim 8, provided the other claim elements are satisfied.

Other insulin secretagogues

Claim 12 identifies additional insulin secretion enhancers, including glimepiride and two chemically defined compounds. The claim is relevant because it expands the practical combination set beyond glibenclamide.

What is the patent’s claim hierarchy?

The claim hierarchy can be summarized as follows:

Claim 1
Broad method:
claimed insulin-sensitizing compound + insulin secretion enhancer

Claims 2 and 3
Narrower compound embodiments, including pioglitazone

Claim 4
Insulin secretion enhancer is glibenclamide

Claim 5
Pioglitazone + glibenclamide

Claim 6
Specific named thiazolidinedione-related compound

Claim 7
Troglitazone

Claim 8
Insulin secretion enhancer is a sulfonylurea

Claim 9
Enumerated sulfonylureas

Claims 10 and 11
Detailed limitations on the R' substituent and heterocyclic groups

Claim 12
Specified non-gliclazide insulin secretion enhancers, including glimepiride

Claims 5, 8 and 9 are narrower but easier to map to commercial products. Claim 1 has broader theoretical coverage but is more exposed to prior-art, written-description, enablement and claim-construction challenges.

How strong was the patent estate for pioglitazone combination therapy?

The patent estate was stronger as a historical formulation and combination strategy than as a current market barrier.

Strengths

Claim 3 expressly identified pioglitazone.
Claim 5 targeted the commercially recognizable pioglitazone-glyburide combination.
Claim 8 covered the sulfonylurea class.
The claims addressed a clinically relevant rationale: reducing the amount of each active component while retaining therapeutic effect.
The method claims could potentially reach branded labeling that instructed combination use.

Weaknesses

The claims were method claims rather than composition claims.
The broad genus in claim 1 created potential written-description and enablement questions.
“Reducing the amount” may require evidence comparing combination treatment with component monotherapy or prior dosing.
Several insulin secretion enhancers were old and widely used before the patent.
The combination of an insulin sensitizer and a sulfonylurea was vulnerable to obviousness arguments based on known complementary mechanisms.
Once the patent expired, these issues became commercially immaterial except in historical litigation or validity analysis.

When did US Patent 6,211,205 lose exclusivity?

US 6,211,205 lost patent exclusivity in 2018. The patent is expired and cannot support a new Paragraph IV challenge or a current injunction against a generic product.

The patent’s expiration must be distinguished from other pioglitazone patents. Actos and related pioglitazone products were protected by separate compound, formulation and use patents, including patents associated with Takeda’s original pioglitazone franchise. Expiration of US 6,211,205 did not by itself determine generic entry for pioglitazone monotherapy.

Exclusivity timeline

Event	Timing
Priority and filing period	Late 1990s
U.S. patent issuance	April 3, 2001
Primary commercial product	Pioglitazone, marketed as Actos
Hatch-Waxman relevance	Method-of-use and combination patent
Patent expiration	2018
Current patent status	Expired
Current generic launch risk from this patent	No blocking risk

FDA regulatory exclusivity and patent exclusivity are separate. New chemical entity exclusivity, pediatric exclusivity, listed patents and regulatory exclusivity periods do not revive an expired patent. [2][3]

What was the Orange Book status of the patent?

The Orange Book status must be evaluated at the product level, not solely by patent number. A patent may be listed against an NDA if it claims the approved drug, an approved formulation or an approved method of use. A method claim covering a combination not reflected in the approved labeling may face listing limitations.

For pioglitazone products, the relevant Orange Book analysis historically included:

The Actos NDA;
Listed patents directed to pioglitazone or its use;
Combination-use patents;
Pediatric exclusivity;
Generic certifications filed against listed patents.

US 6,211,205 is now expired. Any historical Orange Book listing no longer creates a live patent obstacle. Current applicants cannot be required to wait for the expiration of this patent before launching a product that otherwise satisfies FDA requirements.

An ANDA applicant seeking approval for pioglitazone or a combination product would separately assess all currently listed patents, if any, and select a Paragraph I, II, III or IV certification as appropriate under the Hatch-Waxman framework. [3][4]

Which companies challenged pioglitazone exclusivity?

Generic manufacturers challenged the remaining Actos patent estate through ANDA filings and Paragraph IV certifications. The principal competitive set included major generic manufacturers such as:

Teva Pharmaceuticals;
Mylan;
Watson or Actavis;
Ranbaxy;
Sun Pharmaceutical; and
Other ANDA sponsors.

The relevant disputes focused primarily on other Actos patents, including compound, polymorph, formulation or use patents, rather than on US 6,211,205 as a current barrier. Generic pioglitazone became broadly available after the expiration or resolution of the principal Actos patents.

No current Paragraph IV litigation against US 6,211,205 is commercially meaningful because the patent has expired.

What patent litigation and settlements affected the market?

The commercial litigation surrounding pioglitazone involved Takeda’s broader Actos estate. Typical issues included:

Validity of pioglitazone patents;
Infringement by generic tablets;
Paragraph IV certifications;
Launch dates negotiated through settlement;
Authorized generic arrangements;
Formulation and polymorph claims;
Regulatory exclusivity; and
Product liability litigation involving Actos.

A settlement concerning a separate Actos patent would not automatically resolve or invalidate US 6,211,205. Conversely, expiration of US 6,211,205 would not eliminate disputes involving later-expiring patents.

The subject patent should therefore be treated as one historical layer in the Actos portfolio, not as the principal patent controlling generic pioglitazone entry.

What formulation patents are relevant to pioglitazone?

US 6,211,205 does not claim a tablet formulation, excipient system, dissolution profile or manufacturing process. It is therefore distinct from:

Tablet-composition patents;
Controlled-release formulations;
Fixed-dose combination tablets;
Salt or polymorph patents;
Crystalline-form patents;
Process patents; and
Stability or packaging patents.

A company developing a pioglitazone combination product would need a separate freedom-to-operate review covering the exact drug product, strength, dosage form, manufacturing process and labeling. The expired combination-method patent does not clear those other categories.

Does the patent create biosimilar risk?

No. Pioglitazone and glibenclamide are small-molecule drugs, not biologics. The Biologics Price Competition and Innovation Act biosimilar pathway does not apply.

The relevant competitive pathways are:

ANDA approval for a therapeutically equivalent generic;
505(b)(2) approval for a product with changes requiring reliance on existing data;
NDA approval for a new fixed-dose combination; and
State-substitution rules after FDA approval and Orange Book therapeutic-equivalence designation.

What generic launch scenarios exist after expiration?

The expired patent supports several low-risk commercial scenarios:

Product strategy	Relevance of US 6,211,205
Generic pioglitazone monotherapy	No current barrier
Generic glyburide monotherapy	No current barrier
Separate pioglitazone and sulfonylurea prescriptions	No current barrier
Fixed-dose pioglitazone-glyburide product	No current barrier from this patent
Pioglitazone plus glimepiride regimen	No current barrier from this patent
New modified-release combination	Requires separate formulation review
New indication or dosing regimen	Requires separate method-patent review
Non-U.S. launch	Requires country-specific patent and regulatory review

The principal remaining risks are regulatory, clinical and commercial rather than exposure under US 6,211,205. These include proof of bioequivalence, dosage-form development, manufacturing cost, market demand, reimbursement, and competing diabetes therapies.

How does this patent compare with competing diabetes patent estates?

Patent estate	Primary protection	Current relevance
US 6,211,205	Combination method using insulin sensitizer and secretagogue	Expired
Actos compound estate	Pioglitazone chemical entity and related uses	Historical; principal patents expired
Sulfonylurea estates	Older chemical compounds and formulations	Generally expired
DPP-4 inhibitor estates	Sitagliptin, saxagliptin, linagliptin and related uses	Separate, drug-specific analysis
SGLT2 inhibitor estates	Empagliflozin, dapagliflozin and related combinations	Separate, often later-expiring estates
GLP-1 receptor agonist estates	Peptide composition, formulation and device claims	Active or recently expiring depending on product
Insulin product estates	Formulation, delivery device and manufacturing claims	Product-specific and jurisdiction-specific

US 6,211,205 had limited defensive value against newer diabetes classes because its claims depend on the defined compound genus and an insulin secretion enhancer. It does not broadly cover combinations involving DPP-4 inhibitors, SGLT2 inhibitors or GLP-1 receptor agonists unless a particular compound satisfies the claim structure.

What geographic coverage does the patent have?

The U.S. patent has only U.S. legal effect. Related patent-family members may have existed in Japan, Europe and other jurisdictions, but their scope, prosecution history, expiration and enforceability must be assessed separately.

Expiration in the United States does not establish freedom to operate in:

Japan;
European Union member states;
Canada;
China;
India;
Australia; or
Other national markets.

A global launch requires a country-by-country review of national-phase patents, supplementary protection certificates, pediatric extensions, divisionals and local litigation.

Key Takeaways

US 6,211,205 claims combination treatment for diabetes using an insulin-sensitizing compound and an insulin secretion enhancer.
Pioglitazone plus glibenclamide is the principal commercial embodiment.
Claim 1 is a broad Markush method claim; claim 5 is the narrowest and most commercially direct pioglitazone-glybenclamide claim.
Claims 8 and 9 extend the combination concept to sulfonylureas.
The patent is a method patent, not a formulation, manufacturing or device patent.
The patent expired in 2018 and presents no current U.S. blocking risk.
It is not a biosimilar patent issue because both principal drugs are small molecules.
Current diligence should focus on other pioglitazone patents, product-specific Orange Book entries, formulation rights and non-U.S. family members.
The supplied text omits the formula for claim 2 and appears to contain a transcription error in claim 6. Those portions should not be used for precise chemical-structure mapping.

Frequently Asked Questions

Is US 6,211,205 still enforceable against a pioglitazone generic?

No. The patent expired in 2018 and cannot support a current infringement injunction.

Did US 6,211,205 cover Actos monotherapy?

No. The claims require combination treatment with an insulin secretion enhancer. Pioglitazone alone does not satisfy the combination element.

Does claim 5 cover a fixed-dose pioglitazone-glyburide tablet?

Potentially, if the tablet is administered as part of the claimed treatment method. The expired status means the claim no longer blocks commercialization.

Can a generic company rely on the patent’s expiration without reviewing other Actos patents?

No. Other patents may have covered pioglitazone compounds, formulations, methods of use or specific products. Each listed patent requires separate analysis.

Does the patent cover pioglitazone combined with metformin?

Not expressly under the supplied claims. Metformin is an insulin sensitizer, not generally an insulin secretion enhancer of the type required by these claims. A particular combination would require analysis under the exact claim language and the approved treatment instructions.

References

United States Patent and Trademark Office. (2001). U.S. Patent No. 6,211,205, Remedy for diabetes.
United States Code, 35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulations and patent certification requirements, 21 C.F.R. §§ 314.94, 314.107.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	7-153500	Jun 20, 1995

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0861666	⤷ Start Trial	91298	Luxembourg	⤷ Start Trial
European Patent Office	0861666	⤷ Start Trial	300258	Netherlands	⤷ Start Trial
European Patent Office	0861666	⤷ Start Trial	SPC 038/2006	Ireland	⤷ Start Trial
European Patent Office	0861666	⤷ Start Trial	07C0006	France	⤷ Start Trial
European Patent Office	0861666	⤷ Start Trial	CA 2007 00001	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,211,205

Summary for Patent: 6,211,205