# United States Patent 6,150,383: Claim Scope, Expiration, Orange Book Status and Generic Entry Risk

US Patent 6,150,383 protects combination treatment using a thiazolidinedione-type insulin-sensitizing compound and an insulin secretion enhancer, particularly pioglitazone or troglitazone combined with a sulfonylurea such as glibenclamide. The patent’s two independent claims cover treatment of lipid metabolism disorders and glycometabolism disorders. Its principal commercial relevance was the use of pioglitazone with sulfonylureas in type 2 diabetes.

The patent expired in 2016 based on its U.S. filing date, absent an applicable patent-term adjustment or extension. It no longer creates a current U.S. barrier to generic pioglitazone, glyburide, or related combination therapy. No biosimilar pathway applies because the covered products are small-molecule drugs.

What does US Patent 6,150,383 cover?

US 6,150,383 covers a treatment method that requires two therapeutic components:

A thiazolidinedione-related compound within a broad chemical formula; and
An insulin secretion enhancer administered in combination with that compound.

The patent assigns the first component a broad Markush structure. The structure permits variation in:

The hydrocarbon or heterocyclic group designated R';
The carbonyl, hydroxyl-bearing, or amino-containing Y group;
The number of ring or linker units;
The presence of carbon or nitrogen at position X;
The divalent aliphatic linker A;
Oxygen or sulfur at Q;
Alkyl substitution at R1;
Additional substitution on ring E; and
Ring closure involving substituents L, M and R1.

The claims include a proviso excluding one specifically defined benzopyran-related structure. That exclusion narrows the Markush formula but does not materially change the patent’s principal commercial focus: combination therapy involving thiazolidinediones and insulin secretagogues.

What are the independent claims?

Claims 1 and 10 are the independent claims.

Claim	Disorder treated	Required combination
1	Lipid metabolism disorders	Markush compound plus insulin secretion enhancer
10	Glycometabolism disorders	Markush compound plus insulin secretion enhancer

Claim 1 is directed to lipid metabolism disorders. Claim 10 is directed to glycometabolism disorders, a category that includes disorders of glucose metabolism and type 2 diabetes.

Neither independent claim is limited to pioglitazone. Both begin with the broad chemical formula and then require combination administration with an insulin secretion enhancer.

How do the dependent claims narrow Patent 6,150,383?

Claims 2 through 9 narrow claim 1. Claims 11 through 18 mirror those limitations for claim 10.

Dependent claims	Limitation
2, 11	A specified compound represented by the unidentified structural formula in the patent drawing
3, 12	Pioglitazone
4, 13	Glibenclamide, known in the U.S. as glyburide
5, 14	Pioglitazone plus glibenclamide
6, 15	A separately identified thiazolidinedione compound
7, 16	Troglitazone
8, 17	A sulfonylurea
9, 18	A closed or enumerated list of sulfonylureas

Claims 5 and 14 are the most commercially specific claims because they expressly identify pioglitazone and glibenclamide as the combination. Claims 3 and 12 are broader in one respect: they require pioglitazone but leave the insulin secretion enhancer open to the scope of the independent claim.

Claims 8 and 17 cover a sulfonylurea generally. Claims 9 and 18 list particular sulfonylureas, including tolbutamide, chlorpropamide, tolazamide, acetohexamide, glibenclamide, gliclazide, glipizide, gliquidone and related compounds.

The claim text supplied for claim 6 contains apparent transcription or OCR errors, including missing brackets and an inconsistent chemical name. The controlling scope is the issued patent text and its structural drawing, not a reformatted transcription.

What is the technical scope of the patent?

The patent is a pharmacological combination patent, not a composition-of-matter patent for pioglitazone.

The claimed therapy combines:

An insulin sensitizer, principally a thiazolidinedione; and
An insulin secretagogue, principally a sulfonylurea.

The intended pharmacology is complementary. Thiazolidinediones improve insulin sensitivity through PPAR-gamma-related mechanisms. Sulfonylureas stimulate pancreatic insulin secretion. The claims therefore target combined control of glucose metabolism rather than the chemical identity of a new active ingredient.

Does the patent cover pioglitazone monotherapy?

No. Pioglitazone alone does not satisfy claims 3, 5, 12 or 14 because the claims require an insulin secretion enhancer in combination.

A pioglitazone product could implicate a broader claim only if the treatment use includes the required combination and the compound falls within the relevant Markush scope. A label or clinical use limited to pioglitazone monotherapy would not meet the express combination limitation.

Does the patent cover fixed-dose combination products?

The claims are method claims. They do not expressly require a single tablet, capsule or other fixed-dose product. “In combination with” can cover coadministration of separate products, subject to ordinary claim-construction and infringement requirements.

A fixed-dose pioglitazone-sulfonylurea product would be a particularly direct commercial implementation of claims 5 and 14. Separate prescriptions administered as part of the same treatment regimen could also raise the same method-of-use issue.

When did US Patent 6,150,383 expire?

Event	Date or status
U.S. patent number	6,150,383
Issue date	November 21, 2000
U.S. filing framework	Filed in the mid-1990s under the pre-1995 priority structure relevant to the patent record
Expected statutory term	Approximately 20 years from the relevant U.S. filing date
Expected U.S. expiration	May 2016
Current status	Expired
Patent-term extension relevance	No known current extension preserving enforceability

The patent’s practical exclusivity period has ended. Any historical Orange Book listing did not extend the patent beyond its statutory expiration. Patent expiration removes the enforceable patent right, although it does not erase historical litigation, settlement, or regulatory significance.

The patent should be distinguished from product patents covering pioglitazone itself. Product patents and combination-use patents can have different expiration dates. A generic entrant therefore needed to analyze the entire listed patent set, not only US 6,150,383.

What was the Orange Book status of US 6,150,383?

US 6,150,383 was relevant to the Actos regulatory and patent landscape because it claimed pioglitazone-based combination treatment. The Orange Book lists patents submitted by NDA holders when the patents satisfy FDA listing requirements, including patents relating to the drug substance, drug product or approved method of use.[1]

The key regulatory distinction is:

A drug-substance patent can obstruct approval of a generic product containing the active ingredient.
A method-of-use patent can be addressed through a Paragraph IV certification or a labeling carve-out, depending on the listed use and applicable FDA rules.
A combination-treatment patent does not automatically block approval of a generic labeled only for unclaimed or noninfringing uses.

The exact Orange Book listing history should be read by edition because listings, delistings and expiration coding can change over time. The patent’s expiration means that it is no longer a live U.S. Orange Book exclusivity barrier.

Which Paragraph IV challenges affected pioglitazone?

The major generic challenges to Actos focused on the core pioglitazone product patent and related listed patents. Generic applicants including Mylan and other manufacturers pursued abbreviated new drug application strategies against Takeda’s Actos patent estate. Litigation in the Actos matter included Takeda Pharmaceuticals North America, Inc. v. Mylan Laboratories, Inc. and related cases.[2]

US 6,150,383 presented a narrower issue than the core product patent:

A generic pioglitazone applicant did not necessarily need to challenge the combination patent if its proposed labeling excluded the patented combination use.
A Paragraph IV certification could be relevant if the applicant’s label included a use covered by the listed patent.
A section viii statement or labeling carve-out could reduce exposure where the FDA-approved labeling permitted omission of the patented method.
Continued prescribing by physicians outside the carved-out label could create separate induced-infringement questions, but the patent’s expiration eliminated that forward-looking risk.

The litigation history surrounding Actos should not be treated as proof that every patent in the Actos Orange Book set was asserted or adjudicated in the same proceeding.

What formulation patents are associated with this patent?

US 6,150,383 is not primarily a formulation patent. It does not claim:

Tablet excipient systems;
Controlled-release matrices;
Enteric coatings;
Particle-size distributions;
Specific dissolution profiles;
Manufacturing processes for a tablet; or
A fixed-dose tablet composition as such.

Its protection is based on the therapeutic method and the selected active ingredients. A separate formulation patent could have protected a particular dosage form, but that would require independent analysis of the relevant patent family and Orange Book entries.

For generic development, the distinction matters. A formulation design-around does not avoid a method claim if the same active ingredients are administered for the claimed combination use. Conversely, a generic may avoid a formulation patent while still needing to address method-of-use or drug-substance patents.

How strong was the patent estate for pioglitazone combination therapy?

The estate had moderate historical strength as a combination-use position but limited breadth against generic pioglitazone monotherapy.

Strength factor	Assessment
Chemical breadth	Broad Markush language in claims 1 and 10
Commercial specificity	Strongest in claims 5 and 14, covering pioglitazone plus glibenclamide
Treatment limitation	Material narrowing factor because combination administration is required
Product coverage	None for pioglitazone alone
Formulation coverage	Not the central claim type
Generic exposure	Highest where labeling included pioglitazone plus a sulfonylurea
Design-around potential	Available through omission of patented combination uses, subject to FDA labeling rules
Current enforceability	None after expiration

Claims 5 and 14 are easier to map to a commercial regimen but less broad than claims 1 and 10. Claims 1 and 10 provide broader compound coverage but create greater claim-construction and chemical-scope questions.

The requirement for an “insulin secretion enhancer” also creates a potential factual issue. The alleged infringer’s product, label, prescribing information and actual use would need to establish the required combination. A product that contains pioglitazone but omits sulfonylurea combination instructions presents a materially different infringement profile.

How does US 6,150,383 compare with other diabetes patent categories?

Patent category	Typical subject matter	Relevance to US 6,150,383
Product patent	Pioglitazone molecule or salt	Separate and generally broader against all products containing the compound
Combination-use patent	Pioglitazone plus sulfonylurea	Directly aligned with US 6,150,383
Formulation patent	Tablet composition or release profile	Not the principal subject of US 6,150,383
Manufacturing patent	Synthetic route or process control	Not claimed in US 6,150,383
Labeling patent	Specific indication, patient group or dosing schedule	Potentially adjacent, but not identical
Regulatory exclusivity	New chemical entity, clinical investigation or pediatric exclusivity	Separate from patent rights
Biosimilar patent	Biologic product, process or use	Not applicable to pioglitazone

Troglitazone is expressly identified in claims 7 and 16, but its commercial importance declined after Rezulin was withdrawn from the U.S. market in 2000 because of serious liver toxicity concerns.[3] Pioglitazone remained the commercially relevant thiazolidinedione connected to the patent.

What generic launch risks existed under US 6,150,383?

Before expiration, the principal launch scenarios were:

Scenario 1: Generic pioglitazone with combination labeling

A generic label that reproduced pioglitazone plus sulfonylurea treatment instructions could face a listed method-of-use patent issue. The applicant might use Paragraph IV certification, a section viii statement, or a negotiated approach depending on the FDA-listed indication and claim scope.

Scenario 2: Generic pioglitazone with a carve-out

A label omitting the claimed combination use could reduce exposure to claims 3, 5, 12 and 14. The effectiveness of that strategy would depend on the remaining label language, prescribing information, promotional conduct and the precise scope of the listed method.

Scenario 3: Pioglitazone plus a nonlisted insulin enhancer

Claims 1 and 10 are not limited to glibenclamide. They refer to an insulin secretion enhancer broadly. Claims 8 and 17 separately cover sulfonylureas. A combination using another qualifying enhancer could therefore remain within broader claim language, even if it did not use the preferred glibenclamide combination.

Scenario 4: Fixed-dose combination development

A fixed-dose combination would be commercially attractive from a convenience perspective but would have presented a direct claim-mapping risk before expiration. Separate-component coadministration would not necessarily avoid the method claims.

All four scenarios became largely academic after the patent expired in 2016.

What manufacturing and IP barriers remain after expiration?

US 6,150,383 no longer creates a manufacturing barrier. A company can manufacture and market pioglitazone-sulfonylurea combinations without infringing this expired patent.

Remaining barriers may include:

Active pharmaceutical ingredient manufacturing controls;
Nitrosamine or impurity specifications;
Stability and dissolution requirements;
ANDA bioequivalence;
Current labeling requirements;
Other unexpired patents not covered by this analysis;
Trade secrets relating to scale-up or quality control; and
Regulatory obligations concerning pioglitazone safety monitoring.

These issues are commercial and regulatory barriers, not surviving rights under US 6,150,383.

What is the current competitive landscape?

The relevant U.S. market has shifted from originator exclusivity to generic competition.

Product or class	Commercial position
Actos, pioglitazone	Originator product; patent exclusivity ended
Generic pioglitazone	Established generic competition
Pioglitazone plus sulfonylurea	Available through coadministration and, depending on market authorization, combination products
Troglitazone	Withdrawn from the U.S. market
Sulfonylureas	Mature generic class
DPP-4, GLP-1 and SGLT2 products	Competing modern diabetes therapies with separate patent estates

The commercial value of US 6,150,383 was highest when pioglitazone remained protected by core product patents and when combination prescribing represented an important part of Actos sales. After product-patent expiry and generic entry, the combination patent had declining incremental value and then expired.

What are the key takeaways from US Patent 6,150,383?

US 6,150,383 is a method-of-treatment patent, not a pioglitazone composition-of-matter patent.
Its independent claims cover treatment of lipid metabolism and glycometabolism disorders.
The required therapy combines a thiazolidinedione-type compound with an insulin secretion enhancer.
Pioglitazone is expressly covered in claims 3, 5, 12 and 14.
Glibenclamide is expressly covered in claims 4, 5, 13 and 14.
Sulfonylureas are covered broadly in claims 8 and 17 and through an enumerated list in claims 9 and 18.
The most commercially direct claims are claims 5 and 14, covering pioglitazone plus glibenclamide.
The patent did not block pioglitazone monotherapy.
It was not principally a formulation, manufacturing or fixed-dose composition patent.
The U.S. patent expired in 2016.
No biosimilar analysis is applicable because the products are small molecules.
Current generic entry risk must be assessed against other live patents and FDA requirements, not US 6,150,383.

FAQs about US Patent 6,150,383

Did US 6,150,383 cover Actos by itself?

No. The patent required administration of pioglitazone or another covered compound with an insulin secretion enhancer. Actos monotherapy did not satisfy the combination limitation.

Did US 6,150,383 cover metformin combinations?

The supplied claims do not expressly identify metformin. The independent claims use broader language concerning an insulin secretion enhancer, but whether metformin falls within that term requires analysis of the issued specification, prosecution history and claim construction.

Could a generic omit the pioglitazone-sulfonylurea use from its label?

Before expiration, a generic applicant could evaluate a section viii statement or labeling carve-out if FDA rules permitted omission of the patented use. That strategy depended on the exact Orange Book listing and proposed label.

Was troglitazone a major commercial target of this patent?

No. Although claims 7 and 16 expressly identify troglitazone, Rezulin was withdrawn from the U.S. market in 2000. Pioglitazone was the more important commercial embodiment.

Does expiration of US 6,150,383 eliminate all barriers to a pioglitazone combination product?

No. Expiration eliminates this patent as a barrier. A launch still requires compliance with FDA approval, bioequivalence, labeling, quality and manufacturing requirements and must account for any separate unexpired patent rights.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book). https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Court of Appeals for the Federal Circuit. (2005). Takeda Chemical Industries, Ltd. v. Mylan Laboratories, Inc., 417 F.3d 1355.
U.S. Food and Drug Administration. (2000). FDA announces withdrawal of Rezulin. https://www.fda.gov/
United States Patent and Trademark Office. (2000). U.S. Patent No. 6,150,383: Pharmaceutical composition for treating metabolic disorders. https://patents.google.com/patent/US6150383
U.S. Food and Drug Administration. (2011). Actos prescribing information. https://www.accessdata.fda.gov/ fda.gov/scripts/cder/daf/encore/index.cfm

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
European Patent Office	0861666	⤷ Start Trial	SPC/GB07/009	United Kingdom	⤷ Start Trial
European Patent Office	0861666	⤷ Start Trial	C00861666/01	Switzerland	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,150,383

Summary for Patent: 6,150,383