US Patent 6,197,341: Balsalazide Tablet Claims, Patent Scope, and Generic Entry Risk

US Patent 6,197,341 protects high-density tablets containing balsalazide or broadly defined related compounds, along with methods for treating gastrointestinal disease and manufacturing the tablets. The commercially important subject matter is sodium balsalazide dihydrate compressed into tablets with a density of at least 0.9 mg/mm³. The patent’s strongest practical coverage is directed to the formulation and manufacturing process, not to balsalazide as an active pharmaceutical ingredient.

The patent issued on March 6, 2001. Its claims are materially narrower than a compound patent because they require a tablet dosage form and a specified density. The patent would not, based on the supplied claims alone, block every balsalazide formulation, capsule, suspension, low-density tablet, or alternative dosage form.

What does US Patent 6,197,341 protect?

The patent contains four principal claim categories:

Claim category	Claims	Protected subject matter
Tablet formulation	1-3, 13	A dense tablet containing a covered compound, especially sodium balsalazide dihydrate
Treatment method	4-8, 18-20	Administration of the dense tablet for gastrointestinal disease, including active ulcerative colitis and colon cancer
General manufacturing method	9-12	Granulation, compression, and optional coating of the covered compound
Balsalazide-specific manufacturing method	14-17	Granulation and compression of sodium balsalazide dihydrate into the required-density tablet

The central technical limitation is tablet density. The independent formulation claim requires a tablet having a density of at least 0.9 mg/mm³. Claims 3 and 13 narrow that range to 1.1-1.7 mg/mm³.

Because 1 mg/mm³ equals 1 g/cm³, the density limits correspond approximately to:

Claimed value	Equivalent density
0.9 mg/mm³	0.9 g/cm³
1.1 mg/mm³	1.1 g/cm³
1.7 mg/mm³	1.7 g/cm³

The specification and prosecution history would determine how tablet density must be measured, including whether coating, pores, and tablet geometry are included in the calculation. That measurement issue is material to infringement and validity.

What active ingredients fall within the patent?

The broad chemical definition covers compounds of formula I in which:

X is SO₂ or CO;
R1 is phenyl, carboxymethylphenyl, or R2Y;
R2 is an alkylene or substituted benzyl-alkylene group;
Y is a carboxylic acid, sulphonic acid, hydroxyl, amino, substituted amino, or dialkylamino group;
the compound may be an ester, active metabolite, or pharmaceutically acceptable salt.

Claim 2 narrows the formulation to sodium balsalazide dihydrate. Claims 5 and 14-17 do the same for treatment and manufacturing.

For commercial purposes, sodium balsalazide dihydrate is the relevant species. Balsalazide is a colon-targeted prodrug that is converted in the colon to mesalamine and an inert carrier component. The branded product associated with this technology was Colazal, later marketed as Giazo in a lower-dose regimen. FDA labeling identifies balsalazide disodium as the active ingredient and describes oral capsules and tablets administered for ulcerative colitis indications.[2]

The broad Markush language creates theoretical coverage beyond balsalazide. Its practical enforceability depends on written description, enablement, anticipation, obviousness, and whether the accused compound actually falls within the structural definition.

How strong is the formulation patent estate?

The estate is strongest where a competing product uses all of the following:

Sodium balsalazide dihydrate.
A tablet rather than a capsule or other dosage form.
Granulation before compression.
A tablet density of at least 0.9 g/cm³.
Optional use of a binding agent, compression excipient, or coating.

The estate is weaker against products that avoid one or more of those limitations. A competitor could potentially design around the claims by using:

A capsule filled with granules or powder.
A lower-density tablet.
A different polymorph, hydrate, solvate, or salt, subject to regulatory and equivalence constraints.
Direct compression without the claimed granulation step.
A dosage form that does not satisfy the specified density.
A formulation that uses a different active ingredient outside the structural formula.

The density limitation gives the claims a clear technical boundary, but it also creates potential validity and enforcement issues. Dense tablets were known pharmaceutical dosage forms before the patent’s filing. The patent’s patentability therefore depends on whether the claimed density, combined with sodium balsalazide and the disclosed processing steps, produced an unexpected technical result or solved a recognized manufacturing problem.

What do claims 1-3 and 13 cover?

Claim 1 is the principal product claim. It requires:

A compound within the formula;
An ester, active metabolite, or pharmaceutically acceptable salt;
Excipients or binding agents;
A tablet;
Density of at least 0.9 mg/mm³.

Claim 2 limits claim 1 to sodium balsalazide dihydrate. Claim 3 further limits the density to 1.1-1.7 mg/mm³. Claim 13 repeats the sodium balsalazide and 1.1-1.7 mg/mm³ limitations.

A sodium balsalazide tablet with a density of 1.2 g/cm³ would fall within claims 2, 3, and 13 if the tablet otherwise satisfies the claim language. A capsule containing the same amount of sodium balsalazide would not literally satisfy the tablet limitation.

The claims do not specify a particular tablet weight, release profile, coating composition, dissolution rate, or excipient identity. Those omissions broaden the formulation claims within the density boundary.

What do claims 4-8 cover?

Claims 4-8 are method-of-treatment claims. Claim 4 requires administration of the covered formulation to a patient suffering from gastrointestinal disease. Claims 5 and 6 narrow the active ingredient and density. Claims 7 and 8 specify:

Active ulcerative colitis.
Colon cancer.

The ulcerative-colitis limitation is commercially relevant because FDA approval for balsalazide was directed to active ulcerative colitis. The colon-cancer claim is broader from a therapeutic-use perspective but may face greater scrutiny concerning written description, enablement, clinical support, and whether the specification adequately supports treatment of that disease.

Treatment claims generally create less direct exposure for an ANDA applicant than product and manufacturing claims. Under the Hatch-Waxman framework, an ANDA applicant may use a section viii statement to carve out a patented method of use if the proposed labeling omits the protected indication. That strategy does not avoid product or process claims covering the formulation itself.[3]

What do claims 9-17 cover?

Claims 9-12 cover a manufacturing sequence:

Granulating the covered compound with excipients or binding agents.
Compressing the granulate into a tablet.
Producing a tablet with density of at least 0.9 mg/mm³.
Optionally coating the tablet after compression.

Claims 14-17 provide a more focused manufacturing set for sodium balsalazide dihydrate. Claim 14 requires granulation of sodium balsalazide dihydrate and compression into a tablet meeting the density requirement. Claims 15-17 add binding agents, compression excipients, and coating.

A process claim may be infringed even if the finished product is not independently shown to infringe, provided the accused manufacturing process satisfies every process limitation. Conversely, a generic manufacturer may avoid claims 9-17 by using direct compression, a different granulation approach, or a process that produces a tablet below the density threshold.

The coating limitation is sequential. Claim 12 requires compression before coating. A coating applied before compression, or an integrated process that cannot be characterized as coating after compression, would create a noninfringement position subject to factual analysis.

What do claims 18-20 protect?

Claims 18-20 specify three dosing regimens:

Claim	Tablet count	Tablet weight	Frequency	Total tablet mass per day
18	3	About 750 mg	Three times daily	About 6,750 mg
19	2	About 1,125 mg	Three times daily	About 6,750 mg
20	1	About 2,250 mg	Three times daily	About 6,750 mg

These claims protect alternative ways of delivering approximately the same total daily tablet mass. The claims do not, in the language supplied, expressly state the amount of active sodium balsalazide per tablet. “About” introduces a claim-construction issue concerning permissible weight variation.

The claims are vulnerable to design-around arguments if a competing product uses a different tablet weight or administration frequency. They may also be difficult to enforce against a manufacturer where the label does not require the claimed regimen.

When does US Patent 6,197,341 lose exclusivity?

The patent issued in 2001 and is subject to the modern patent-term framework, generally measured from the earliest effective nonprovisional filing date rather than from issue date. The ordinary term therefore falls in the mid-2010s, subject to patent-term adjustment, terminal disclaimers, patent-term extension, or other term-specific events.[1]

The supplied claim set does not establish the exact expiration date, any patent-term adjustment, or whether the patent received a term extension. Those dates must be determined from the USPTO patent record and the relevant Orange Book historical listing. The patent’s age indicates that it is not a present-day long-term exclusivity barrier in the same manner as a recently issued formulation patent.

What was the Orange Book status of balsalazide products?

Balsalazide products were approved through an NDA pathway, with Colazal associated with FDA approval for active ulcerative colitis. FDA’s Orange Book identifies approved products, patent information submitted by NDA holders, and periods of regulatory exclusivity.[4]

For a generic applicant, the relevant questions are:

Whether US 6,197,341 was listed against the applicable NDA.
Whether the listed patent was active when the ANDA was filed.
Whether the applicant submitted a Paragraph IV certification.
Whether the NDA holder filed an infringement action within 45 days.
Whether any 30-month stay applied.
Whether the proposed generic labeling included or carved out the claimed indications.

FDA Orange Book listing does not establish validity or enforceability. It is an administrative patent-listing mechanism. A patent can be listed while remaining vulnerable to invalidity or noninfringement defenses.

Which companies challenged balsalazide exclusivity?

The commercially relevant competitive field included the branded sponsor and generic manufacturers seeking approval for balsalazide products after the applicable exclusivity and patent barriers declined. FDA approved generic balsalazide products after the branded product’s core exclusivity period, including products associated with manufacturers such as Mylan.[5]

The principal generic-entry question was not whether a manufacturer could make balsalazide. It was whether the proposed product and manufacturing process would meet the tablet-density and granulation limitations. A capsule-based or differently manufactured product would present a different claim analysis from a dense compressed tablet.

The supplied information does not establish a complete list of Paragraph IV filers, litigation defendants, settlements, or launch dates. Those events are separate from the patent claims and cannot be derived from the claim text.

What patent litigation and settlements affect the patent?

Claim text alone does not establish litigation history. A complete litigation analysis would require review of:

PACER district-court complaints and docket entries;
Federal Circuit and district-court opinions;
FDA Paragraph IV notices;
Orange Book patent-listing records;
ANDA approval letters;
Any settlement or license agreements.

The key litigation issues would likely include claim construction for “density,” the meaning of “granulating,” whether the accused product contains sodium balsalazide dihydrate, and whether the manufacturing process includes the claimed sequence.

The most important validity challenges would be:

Issue	Likely focus
Anticipation	Earlier balsalazide tablets or dense tablets containing the claimed compound
Obviousness	Combining known balsalazide formulations with conventional granulation and compression
Indefiniteness	Measurement method for density and scope of “about” in claims 18-20
Written description	Breadth of the Markush formula and colon-cancer treatment claim
Enablement	Ability to make the full claimed genus and all covered tablet formulations
Double patenting	Overlap with related balsalazide or formulation patents

How does this patent compare with compound and method-of-use patents?

US 6,197,341 is a formulation and manufacturing patent. It differs from:

A compound patent, which can block the active ingredient across dosage forms.
A polymorph or salt patent, which can block a particular solid form.
A method-of-use patent, which covers treatment of a specified disease or patient population.
A process patent, which covers a manufacturing route regardless of some finished-product characteristics.

Its commercial blocking power is narrower than a compound patent because the claims require a dense tablet. Its practical value can still be significant if the approved product depends on that tablet architecture and if alternative dosage forms are commercially unattractive.

What generic launch risks exist?

The main generic risks are:

Literal infringement by using sodium balsalazide dihydrate in a compressed tablet.
Infringement based on tablet density of at least 0.9 g/cm³.
Process infringement through wet or dry granulation followed by compression.
Label exposure from the active-ulcerative-colitis indication.
Difficulty demonstrating pharmaceutical equivalence for a redesigned low-density or capsule formulation.
Regulatory delay if the product cannot match the reference product’s dosage form or release characteristics.

The strongest design-around is a product that avoids the tablet and granulation limitations without creating new bioequivalence or manufacturing problems. A low-density tablet may avoid the numeric limitation but could alter disintegration, dissolution, dose uniformity, tablet size, or patient acceptability.

Key Takeaways

US 6,197,341 is principally a dense-tablet formulation and manufacturing patent for sodium balsalazide dihydrate.
The core threshold is 0.9 mg/mm³, equivalent to 0.9 g/cm³.
Claims 3 and 13 narrow the density to 1.1-1.7 mg/mm³.
Claims 14-17 create specific process coverage for granulating and compressing sodium balsalazide dihydrate.
Claims 18-20 cover three high-mass tablet dosing regimens administered three times daily.
The patent does not cover every balsalazide dosage form.
Capsules, low-density tablets, direct-compression products, and alternative manufacturing routes present potential design-around positions.
Treatment claims are less important to generic entry than the product and process claims.
The patent issued in 2001 and its ordinary term falls in the mid-2010s, subject to term adjustments and related legal events.
Exact Orange Book status, Paragraph IV challenges, litigation, settlements, and expiration require the USPTO, FDA, and court records rather than the claim text alone.

FAQs

Does US 6,197,341 cover balsalazide capsules?

No. The supplied independent formulation claims require a tablet. A capsule would not literally satisfy that dosage-form limitation, although other patents or regulatory requirements could still affect the product.

Can a generic manufacturer avoid the patent by using a lower-density tablet?

Potentially. A tablet below 0.9 mg/mm³ would not satisfy the express density limitation, but the manufacturer would need to address bioequivalence, dissolution, tablet size, and any separate patent claims.

Does the patent cover sodium balsalazide monohydrate?

The claims specifically identify sodium balsalazide dihydrate in their narrowed embodiments. Whether another hydrate or solid form falls within the broader chemical language depends on claim construction and the precise identity of the material used.

Are claims 18-20 composition claims?

No. Claims 18-20 are method-of-treatment claims. They define administration regimens involving specified tablet counts and approximate tablet weights.

Is the patent still a likely barrier to a new balsalazide generic?

Based on its 2001 issue date and the ordinary patent-term framework, it is unlikely to provide a current long-duration exclusivity barrier. Its historical relevance remains important for assessing earlier generic filings, litigation, and the development of the approved dosage form.

References

United States Patent and Trademark Office. (2001). U.S. Patent No. 6,197,341, Pharmaceutical formulation.
U.S. Food and Drug Administration. (2012). Colazal (balsalazide disodium) prescribing information.
Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2017). FDA approves first generic balsalazide disodium capsules for ulcerative colitis.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	9700934-4	Mar 14, 1997

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	6430198	⤷ Start Trial
Belgium	1011837	⤷ Start Trial
Brazil	9808140	⤷ Start Trial
Canada	2283297	⤷ Start Trial
European Patent Office	1003524	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,197,341

Summary for Patent: 6,197,341