Details for Patent: 6,329,404

Summary for Patent: 6,329,404

Title:	Pharmaceutical composition
Abstract:	Pharmaceutical composition which comprises an insulin sensitivity enhancer in combination with other antidiabetics differing from the enhancer in the mechanism of action, which shows a potent depressive effect on diabetic hyperglycemia and is useful for prophylaxis and treatment of diabetes.
Inventor(s):	Hitoshi Ikeda, Takashi Sohda, Hiroyuki Odaka
Assignee:	Takeda Pharmaceutical Co Ltd
Application Number:	US09/453,521
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,329,404
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 6,329,404 (US 6,329,404) Scope, Claims, and US Patent Landscape for Insulin Sensitivity + Insulin Secretion Enhancer Combinations

US 6,329,404 claims a diabetes-treatment combination: an insulin sensitivity enhancer defined by a narrow set of 2,4-thiazolidinedione (TZD) derivatives (including specific ethyl-substituted pyridyl-ethoxy benzyl TZDs) in combination with an insulin secretion enhancer defined as sulfonylureas (with a defined supplier set that includes glibenclamide). Independent coverage runs through (i) composition claims and (ii) method-of-treatment claims for diabetes, including specified weight-ratio ranges and a synergy assertion. Practical freedom-to-operate (FTO) depends on whether a candidate product’s insulin sensitivity component is one of the listed TZD structures (or their pharmacologically acceptable salts) and whether the insulin secretion component is one of the enumerated sulfonylureas (or its listed salt form). If both elements match, the patent reaches both mixed admixtures and independently dosed regimens.

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What exactly does US 6,329,404 claim: combination product or just a method for diabetes?

US 6,329,404 has two claim families that map to two common regulatory/commercial embodiments: combination products and treatment methods.

Independent claim structure

• Composition (Claim 1): “A pharmaceutical composition comprising” the two-component combination.
• Method (Claim 13): “A method for treating diabetes in a mammal” via administering a therapeutically effective amount of the same two-component combination.

The breadth is constrained by:

1. The insulin sensitivity enhancer definition (tight structural genus of four specific TZD derivatives, plus pharmacologically acceptable salts).
2. The insulin secretion enhancer definition (a sulfonylurea, with an enumerated list in dependent claims, including glibenclamide).
3. Purpose limitation: diabetes treatment in humans/mammals.
4. Optional quantitative and effect limitations: specific weight ratios (dependent) and “synergistic effect” (dependent).

Key takeaway on claim reach

If a product uses pioglitazone (as a specific dependent route) plus glibenclamide or another enumerated sulfonylurea, it is directly within multiple claim layers (composition + method + ratio + synergy, where applicable). If it uses other insulin sensitivity enhancers outside the listed TZD structures, or insulin secretion enhancers outside sulfonylureas (or outside the enumerated list if the formulation is intended to hit dependent claims), coverage can fall away.

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How broad is the “insulin sensitivity enhancer” definition in US 6,329,404?

The insulin sensitivity enhancer is defined in the independent claims by a small set of structural variants of a TZD scaffold.

Insulin sensitivity enhancer elements (Claim 1 / Claim 13 list)

One of the following:

1. 5-(4-(2-(3-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione or pharmacologically acceptable salt
2. 5-(4-(2-(4-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione or pharmacologically acceptable salt
3. 5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione or pharmacologically acceptable salt
4. 5-(4-(2-(6-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione or pharmacologically acceptable salt

Dependent expansion: pioglitazone route

• Claim 2 (composition) and Claim 14 (method): insulin sensitivity enhancer is pioglitazone or its hydrochloride.

Scope implication

• The independent claims’ structural genus is narrow (four specific ethyl-substituted pyridyl-ethoxy benzyl TZD derivatives).
• The patent also explicitly covers pioglitazone as a dependent embodiment. That matters because pioglitazone is a mainstream TZD; the patent is positioned to capture combination regimens around pioglitazone plus sulfonylureas.

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How broad is the “insulin secretion enhancer” definition in US 6,329,404?

The independent claims require an insulin secretion enhancer that is a sulfonylurea.

Core definition (Claim 3 / Claim 15)

• Insulin secretion enhancer is “a sulfonylurea.”

Dependent enumeration (Claim 4 / Claim 16)

Sulfonylureas listed include:

• tolbutamide, chlorpropamide, tolazamide, acetohexamide
• 4-chloro-N-[(1-pyrolidinylamino)carbonyl]-benzenesulfonamide or its ammonium salt
• glibenclamide
• gliclazide, 1-butyl-3-metanilylurea, carbutamide, glibonuride, glipizide, gliquidone
• glisoxepid, glybuthiazole, glibuzole, glyhexamide, glymidine, glypinamide, phenbutamide, tolcyclamide

Targeted dependent highlight

• Claim 5 (composition) and Claim 17 (method): insulin secretion enhancer is glibenclamide.
• Claim 6 / Claim 18: insulin sensitivity enhancer is pioglitazone (or hydrochloride) and insulin secretion enhancer is glibenclamide.

Scope implication

• “Sulfonylurea” captures a broad class in the independent claim layer, but dependent claims constrain enumerated members.
• Glibenclamide is a named “center-of-gravity” embodiment. Many existing combination products used glibenclamide historically, so this claim architecture aligns with that market.

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Does US 6,329,404 cover admixtures and non-admixture dosing regimens?

Yes. The method claims explicitly cover both common combination modalities.

Admixture route

• Claim 24: insulin sensitivity enhancer and insulin secretion enhancer “are mixed together to form an admixture and the admixture is administered.”

Separate administration route

• Claim 25: insulin sensitivity enhancer and insulin secretion enhancer “are not mixed together … but are administered independently.”

Scope implication

A generic strategy cannot avoid coverage just by separating tablets into distinct dosage forms, if both actives and the structural/class limitations are met. Infringement arguments can be framed around the combination dosing regimen rather than the physical mixing of actives in one dosage form.

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What are the quantitative claim limits: insulin secretion enhancer weight ratios?

Two dependent claim layers specify relative dosing ratios.

Weight parts relative to insulin sensitivity enhancer

• Claim 8 (composition) / Claim 19 (method): insulin secretion enhancer about 0.002 to 5 weight parts per 1 weight part insulin sensitivity enhancer.
• Claim 9 (composition) / Claim 20 (method): insulin secretion enhancer about 0.025 to 0.5 weight parts per 1 weight part insulin sensitivity enhancer.

Scope implication

If a candidate product’s dosing ratio falls outside the stated bands, those dependent claims may not be directly infringed, but independent claim coverage can still exist (since Claim 1 and Claim 13 do not impose those ratios).

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How does the “synergistic effect” limitation work in US 6,329,404?

Two dependent tiers add an effect statement:

• Claim 10-12 (composition): Claim 1 plus synergy; Claim 8 and 9 plus synergy.
• Claim 21-23 (method): Claim 13 plus synergy; Claim 19 and 20 plus synergy.

Scope implication for enforceability

“Synergistic effect” functions as an added limitation. In practice, it can increase evidentiary burden for proving infringement for those dependent claims, but it does not narrow the scope of Claim 1/13 as written (those do not include “synergy”). The strongest litigation position typically comes from the cleanest independent claim match, with synergy potentially used as additional support where the formulation/dosing aligns.

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What patents does US 6,329,404 most likely sit within: combination IP around TZDs + sulfonylureas?

From the claim content alone, the patent is structurally targeted to:

• TZD-based insulin sensitivity enhancers (specific 5-(4-(2-(ethyl-2-pyridyl)ethoxy)benzyl)-2,4-TZD derivatives)
• including a dependent explicit bridge to pioglitazone
• in combination with sulfonylureas, including glibenclamide
• for diabetes treatment via both admixture and independent dosing

Landscape logic (claim-driven)

US 6,329,404 is best treated as a “combination-scope” patent rather than a single-compound composition-of-matter:

• It is not just protecting a single active ingredient.
• It protects a specific paired pharmacology (sensitivity enhancer + secretion enhancer), with chemistry-specific definitions.

This tends to cluster in the broader TZD combination ecosystem where multiple filings exist around:

• TZD derivatives and salts (sensitizer chemistry)
• specific sulfonylureas or their salt forms (secretagogue chemistry)
• fixed-dose or co-pack regimens (formulation and method claims)
• dosing ratio ranges and claims around synergy or additive effects (effect claims)

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What freedom-to-operate risks exist if a company launches a pioglitazone + glibenclamide product?

The combination you flagged is directly mapped into dependent claim coverage.

Most direct infringement touchpoints

• Pioglitazone or pioglitazone hydrochloride as insulin sensitivity enhancer is covered by Claim 2/14.
• Glibenclamide as insulin secretion enhancer is covered by Claim 5/17.
• The pair together is covered by Claim 6 (composition) and Claim 18 (method).

Also relevant

• Both admixture and separate administration are covered in the method claim set (Claim 24 and Claim 25).
• If dosing ratios fall in the specified ranges, dependent layers (Claim 8-9 and Claim 19-20) can add infringement hooks.
• If the regimens meet the “synergistic effect” requirement, additional dependent layers (Claim 10-12, Claim 21-23) become available.

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When does US 6,329,404 lose exclusivity in the US, and what does that mean for generic entry risk?

No expiration/timeline can be produced from the claim text alone. A defensible exclusivity/expiration schedule requires at least the filing date, issue date, and whether there are PTA or related FDA Orange Book-linked regulatory exclusivity. With only the claim set provided, a complete and accurate exclusivity timeline cannot be generated.

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What Orange Book status would likely matter for enforcing US 6,329,404?

A patent’s enforceability against generics typically hinges on whether it is listed in the FDA Orange Book for a specific NDC and drug product, and whether the listed claims match the generic proposed product’s actives and conditions of use.

US 6,329,404 is a combination-scope patent built around:

• actives that include pioglitazone and glibenclamide
• a method-of-use diabetes treatment scope
• and physical/administration modalities (admixture and independent dosing)

However, determining the exact Orange Book listing status cannot be done from the claim excerpt alone.

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How do potential biosimilar or biologic pathways relate to US 6,329,404?

US 6,329,404 is framed as pharmaceutical compositions and methods using small-molecule oral diabetes drugs (TZDs and sulfonylureas). It is not a biologics/Biosimilar claim set and does not map to a biosimilar approval pathway on its face.

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How strong is the patent estate coverage for combination regimens: composition versus method

Based on claim construction:

• The patent has two independent claim anchors (composition + method). This strengthens enforcement flexibility because it can be asserted against product formulation and against dosing regimens.
• The insulin sensitivity and secretion components are defined in ways that reduce ambiguity: specific structural TZD variants and a sulfonylurea class, with explicit dependent enumeration.

Where enforceability can tighten

• Dependent claims with pioglitazone and glibenclamide reduce argument risk by naming the market-relevant actives.
• Dependent claims with synergy and ratio ranges can introduce evidentiary and infringement-detail questions. Independent claims are cleaner for scope matching.

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Which claim elements are most critical for infringement analysis? (Practical mapping)

For a candidate product/regimen, infringement analysis should focus on five “gates”:

1. Is the insulin sensitivity enhancer one of the listed TZD derivatives (or salt), or is it pioglitazone/pioglitazone hydrochloride?
2. Is the insulin secretion enhancer a sulfonylurea?
3. Is the insulin secretion enhancer specifically within the enumerated members if the case relies on dependent claim paths?
4. Is the intended therapeutic use diabetes treatment in a mammal/human?
5. Is the regimen delivered as an admixture or separately administered components? (Both are covered by Claims 24-25, so route of administration is not a clean design-around.)

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Key Takeaways

• US 6,329,404 is a combination patent covering a TZD-based insulin sensitivity enhancer (four specific TZD derivatives plus a dependent pathway to pioglitazone/pioglitazone hydrochloride) combined with a sulfonylurea insulin secretion enhancer.
• The claim set includes composition and method-of-use coverage and expressly covers both admixture and independent dosing regimens.
• Glibenclamide and the pioglitazone + glibenclamide pairing are directly called out in dependent claims (Claim 6 and Claim 18).
• Dependent claims add weight ratio ranges (0.002 to 5; 0.025 to 0.5 secretion enhancer parts per 1 sensitivity enhancer part) and synergy language, which can matter for claim-by-claim infringement proofs.
• An accurate exclusivity/Orange Book/generic launch risk assessment cannot be produced from the provided claim text alone.

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FAQs

Does US 6,329,404 require the actives to be in one tablet

No. Method claims cover both mixed admixtures (Claim 24) and independently administered components (Claim 25).

Is pioglitazone + glibenclamide specifically protected

Yes. Pioglitazone/pioglitazone hydrochloride with glibenclamide is specifically recited in dependent claims for both composition (Claim 6) and method (Claim 18).

What if the insulin sensitivity component is a different TZD

Independent claims are limited to the listed TZD derivatives (four named structures) and the salt forms, and pioglitazone is covered in a dependent claim route. A different TZD not falling within those definitions is not covered by the provided claim set.

Are weight ratios required for all infringement

No. The weight ratio ranges are in dependent claims (Claim 8-9 and Claim 19-20). Independent claims (Claim 1 and Claim 13) do not impose those ratios.

Is “synergy” required to infringe the independent claims

No. “Synergistic effect” is in dependent claims only (Claim 10-12 and Claim 21-23). Independent claims do not include the synergy limitation as written.

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References

1. US Patent 6,329,404.

Drugs Protected by US Patent 6,329,404

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,329,404

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0861666		91298	Luxembourg
European Patent Office	0861666		300258	Netherlands
European Patent Office	0861666		SPC 038/2006	Ireland
European Patent Office	0861666		07C0006	France
European Patent Office	0861666		CA 2007 00001	Denmark
European Patent Office	0861666		SPC/GB07/009	United Kingdom