US Patent 5,252,341: Mesna Granulate Claims, Expiration, and Patent Landscape

US Patent 5,252,341 protects mesna granules made with specified quantities of binding agents and, in dependent claims, lubricants, fillers, flavoring agents, sweeteners, aromatizing substances, and pharmaceutical coatings. Its process claims cover wet granulation using C1-C4 alcohols, acetone, water-containing solvent mixtures, drying, coating, and addition of palatability agents.

The patent issued on October 12, 1993, and its pre-URAA 17-year term expired on October 12, 2010, absent a term adjustment or other extension. The patent therefore does not create a current US exclusion right. Its principal commercial significance is historical: it addressed the manufacture and oral acceptability of mesna granules rather than mesna's chemical composition or therapeutic use.

What does US Patent 5,252,341 cover?

The patent covers two related subject-matter groups:

Mesna granule compositions.
Processes for making those granules.

Mesna is sodium 2-mercaptoethanesulfonate, a thiol-containing uroprotective agent used to reduce urothelial toxicity associated with ifosfamide and, in some settings, cyclophosphamide.

The claims do not broadly cover mesna as an active pharmaceutical ingredient. They focus on mesna in granulated form and on specific excipient ratios and solvent-assisted processing steps.

Claim group	Claims	Subject matter
Composition	1	Mesna granulate with 0.1-1 parts binder per part mesna
Composition	2	Claim 1 plus specified lubricant and filler ranges
Composition	3	Claim 1 or 2 plus flavoring, sweetening, or aromatizing material
Composition	4	Claim 1 or 2 with a pharmaceutically acceptable film coating
Process	5	Granulation using binder and C1-C4 alcohol, acetone, water, or mixtures
Process	6	Claim 5 with filler and/or lubricant
Process	7	Claim 5 or 6 with drying
Process	8	Claim 7 with coating
Process	9	Drying followed by addition and homogenization of palatability agents
Process	10	Claim 9 with pharmaceutical coating

The claim structure is cumulative. A dependent claim requires every limitation of the claim from which it depends, plus the added limitation.

What are the key limitations of independent claim 1?

Claim 1 requires a granulate containing:

Mesna as the active ingredient; and
0.1-1 parts by weight of a binding agent for each part by weight of mesna.

The claim does not specify a particular binder. It therefore potentially covers multiple pharmaceutically acceptable binders, provided the accused product satisfies the ratio and granulate requirements.

The ratio is central. For every 1 part by weight of mesna, the composition must contain between 0.1 and 1 part by weight of binder. The endpoints are included under ordinary patent-claim construction unless the patent or prosecution history indicates otherwise.

Examples:

Mesna quantity	Claimed binder range under claim 1
100 mg	10-100 mg
500 mg	50-500 mg
1 g	0.1-1 g
10 kg	1-10 kg

A product with 0.05 parts binder per part mesna would fall outside the literal range of claim 1. A product with exactly 0.1 or 1 part binder would ordinarily fall within the range.

Claim 1 does not expressly require:

A solvent;
Wet granulation;
Drying;
A lubricant;
A filler;
A coating;
A flavoring agent; or
A particular dosage form.

That breadth distinguishes the composition claim from the process claims.

What additional excipients are protected by claims 2 through 4?

Claim 2: lubricant and filler

Claim 2 adds a lubricant and a filling agent to claim 1. It specifies:

0.01-0.2 parts lubricant per part mesna; and
0.1-1 parts filler per part mesna.

The claim language uses “a member of the group consisting of” for the lubricant and filler categories. The claim therefore requires the presence of at least one lubricant and at least one filling agent within the specified quantitative framework.

For 1 part mesna, claim 2 requires:

Component	Claimed amount
Binding agent	0.1-1 parts
Lubricant	0.01-0.2 parts
Filling agent	0.1-1 parts

The patent claims do not identify the specific chemical members in the claim text supplied. The specification and prosecution history would control the interpretation of “binding agent,” “lubricant,” and “filling agent,” including whether conventional pharmaceutical excipients are incorporated by technical meaning or express disclosure.

Claim 3: palatability agents

Claim 3 covers a granulate under claim 1 or claim 2 that contains at least one of:

A flavoring substance;
A sweetening substance; or
An aromatizing substance.

The claim does not establish a quantitative range for those agents. A small amount may be sufficient if it is technically present and performs the claimed function or falls within the relevant claim construction.

Claim 4: film-coated granulate

Claim 4 covers a granulate under claim 1 or claim 2 coated with a conventional pharmaceutically acceptable film.

The claim does not require the film to be enteric, sustained-release, moisture-barrier, or taste-masking. A conventional pharmaceutical film coating could include a polymeric coating system used for appearance, handling, protection, or palatability, depending on the specification's disclosure.

What processes are protected by claims 5 through 10?

Claim 5 is the principal process claim. It requires:

Mesna;
A binding agent in an amount of 0.01-1 parts per part mesna;
Granulation of mesna and at least part of the binder; and
A granulating liquid consisting of:
- One or more C1-C4 alcohols;
- Acetone;
- A mixture of one of those organic agents with water; or
- Potentially a mixture of the listed organic agents with water.

The process claim is broader in binder quantity at its lower end than composition claim 1. Claim 5 begins at 0.01 parts binder, while claim 1 begins at 0.1 parts.

Process claim comparison

Feature	Composition claim 1	Process claim 5
Mesna	Required	Required
Granulate	Required	Result of claimed process
Binder range	0.1-1 parts	0.01-1 parts
Specified solvent	Not required	Required
Granulation step	Not expressly required	Required
Drying	Not required	Not required in claim 5
Coating	Not required	Not required in claim 5

A process using only water may fall outside claim 5 if the claim is construed to require at least one listed organic agent, because the text specifies C1-C4 alcohols or acetone, or a mixture involving water. A process using ethanol-water, isopropanol-water, acetone-water, methanol, ethanol, propanol, butanol, or acetone is more likely to satisfy the solvent limitation, subject to the full specification and prosecution history.

A dry-compaction process with no listed granulating liquid would not ordinarily satisfy the literal solvent limitation of claim 5.

How do claims 6 through 10 narrow the manufacturing process?

Claim 6 adds a filler, a lubricant, or both. The claim text supplied states:

0.1-1 parts filler per part mesna; and/or
0.1-0.2 parts lubricant per part mesna.

This differs from claim 2, which states a lubricant range of 0.01-0.2 parts. The discrepancy matters. Claim 6's stated lower limit of 0.1 parts is narrower than claim 2's 0.01-part lower limit.

Claim 7 adds drying. The drying step is not required by claim 5 or claim 6 unless incorporated through claim dependency.

Claim 8 adds application of a pharmaceutically acceptable coating to the dried granulate.

Claim 9 requires:

Drying;
Addition of flavoring, sweetening, or aromatizing agents; and
Homogenization of the entire mixture.

Claim 10 adds a pharmaceutically acceptable coating to the homogenized product.

The process claims therefore create several potential design-around paths, including:

Dry granulation without the claimed solvent;
A binder quantity below 0.01 parts or above 1 part per part mesna;
A solvent outside the listed C1-C4 alcohol or acetone categories;
Omission of the claimed drying or coating steps where required;
Addition of palatability agents without the claimed homogenization step; or
Use of a different manufacturing sequence.

Because the patent expired, these design-around points have no current US infringement-avoidance value for this patent. They remain relevant for understanding the patent's historical scope and for evaluating related patent families.

When did US Patent 5,252,341 lose exclusivity?

US Patent 5,252,341 issued on October 12, 1993. For a pre-URAA patent, the ordinary term was 17 years from grant under the former version of 35 U.S.C. § 154. On that basis, the patent expired on October 12, 2010.

Event	Date
US patent grant	October 12, 1993
Ordinary 17-year term	October 12, 2010
Current status	Expired
Current enforceable patent term	None

The patent cannot support a new US infringement action based on commercial activity occurring after expiration. The expiration also removes the patent from the set of live US exclusivity rights that could block a generic or reformulated mesna product.

The patent's expiration does not, by itself, establish that every related foreign patent expired on the same date. Foreign family members are governed by local term rules, filing dates, supplementary protection certificates, and national prosecution histories.

What is the Orange Book status of the mesna granulate patent?

US Patent 5,252,341 is not a current US Orange Book barrier based on its expiration. Orange Book listing rules apply to patents submitted for approved drug products, including qualifying patents covering the drug substance, drug product, or approved method of use. Manufacturing-process patents generally do not receive the same Orange Book role as drug-product or method-of-use patents. FDA, 2024.

The patent claims a granulated dosage-form composition and manufacturing processes. They do not claim:

Mesna's chemical structure as a drug substance;
A broad therapeutic method for preventing urotoxicity;
A specific approved indication;
A specific labeled dosage regimen; or
A broad mesna product independent of granulation.

Any historical listing question must be assessed against the specific approved NDA, patent submission date, and FDA listing records. The patent's 2010 expiration means that any historical Orange Book listing would no longer provide current patent-based market exclusivity.

Does mesna have biosimilar risk?

No conventional biosimilar pathway applies to mesna. Mesna is a chemically synthesized small molecule, not a biologic subject to the Public Health Service Act's biosimilar framework.

Competitive entry would generally involve:

An abbreviated new drug application under section 505(j);
A suitability petition only if applicable to product-specific circumstances;
A 505(b)(2) application for certain differences requiring reliance on existing safety or efficacy information; or
A full 505(b)(1) application.

The principal regulatory issues would be dosage form, route of administration, strength, inactive ingredients, bioequivalence, labeling, and product-specific manufacturing controls. The patent does not create a current regulatory barrier to any of those pathways.

Which companies are challenging the patent?

No current Paragraph IV challenge to US Patent 5,252,341 is commercially material because the patent expired in 2010. A Paragraph IV certification is directed to a listed patent that remains relevant to approval and launch. An expired patent generally cannot delay approval through the Hatch-Waxman 30-month stay mechanism.

A historical challenge may have existed during the patent's term, but the supplied record does not establish a specific ANDA filer, litigation docket, settlement agreement, or court decision. The patent's present commercial status is therefore unaffected by any historical Paragraph IV activity.

What patent litigation affects US Patent 5,252,341?

The patent's expiration eliminates present infringement exposure under the patent. Any historical litigation would require a verified district-court docket or Federal Circuit record.

The principal litigation questions would have been:

Whether the accused product was a “granulate.”
Whether mesna and binder quantities fell within the claimed ranges.
Whether the selected excipient qualified as a binding, filling, or lubricating agent.
Whether a process used one of the specified organic solvents.
Whether the accused process included granulation of mesna and at least part of the binder.
Whether the claims were anticipated or obvious in view of prior mesna formulations and conventional pharmaceutical granulation.

The broad terminology in the claims could have created claim-construction disputes. The quantitative ranges provide measurable limitations, but the absence of named binders, fillers, lubricants, and film-forming materials leaves room for disputes over technical meaning and specification support.

How strong was the patent estate?

The patent estate was narrow in subject matter but potentially useful commercially during its term.

Strength factor	Assessment
Active ingredient claim	Limited to mesna in granulate form
Broad composition coverage	Moderate, because claim 1 does not require solvent, drying, coating, or flavoring
Excipient coverage	Broad terminology, but dependent on technical definitions
Process coverage	Moderate, constrained by specified solvents and steps
Dosage-form coverage	Focused on granules, including coated and palatability-enhanced forms
Chemical-composition protection	None apparent from the supplied claims
Method-of-use protection	None apparent from the supplied claims
Current enforceability	None after 2010 expiration
Biosimilar relevance	None
Generic-entry relevance today	No blocking effect

The strongest historical claim was likely claim 1 because it covered a mesna granulate based on a binder ratio without requiring the additional excipients or processing steps found in the dependent claims. The main vulnerability would have been prior art showing mesna granulation with conventional binders within the claimed range.

The process claims provided a separate enforcement theory against a manufacturer whose final product could be difficult to distinguish from a noninfringing granulate. Their weakness was the requirement for specific organic solvents or solvent-water mixtures and the claimed process sequence.

What manufacturing and intellectual-property barriers remain?

US Patent 5,252,341 does not create a current manufacturing barrier. Commercial barriers may instead arise from:

FDA approval requirements;
Product-specific bioequivalence;
Control of mesna raw material quality;
Stability of thiol-containing formulations;
Moisture and oxidation control;
Taste and patient acceptability;
Granulation scale-up;
Cleaning validation;
Process reproducibility;
Supplier qualification; and
Other unexpired patents not identified in the supplied claims.

The patent does not establish freedom to operate for every mesna product. A company commercializing mesna tablets, oral granules, solutions, injections, or combination products would need to assess separate patents covering formulations, dosage regimens, manufacturing methods, packaging, device systems, and approved methods of use.

Key Takeaways

US Patent 5,252,341 claims mesna granulates and processes for producing them.
Claim 1 requires 0.1-1 parts binding agent per part mesna.
Claims 2-4 add lubricants, fillers, palatability agents, or pharmaceutical film coatings.
Claim 5 requires solvent-assisted granulation using a C1-C4 alcohol, acetone, or an applicable water-containing mixture.
Claims 6-10 add excipients, drying, flavoring or sweetening, homogenization, and coating steps.
The patent issued on October 12, 1993, and its ordinary term expired on October 12, 2010.
The patent has no current US exclusionary force.
It is not a biosimilar patent and does not create a present Paragraph IV or Orange Book launch barrier.
No method-of-use, mesna chemical-composition, or broad therapeutic-use claim appears in the supplied claims.
Current mesna freedom-to-operate analysis must focus on other unexpired patents, FDA requirements, and product-specific manufacturing controls.

FAQs

Can a company market a mesna granulate using the same binder ratios today?

Yes, the expired US patent does not prevent commercial use of the claimed composition or process in the United States.

Does the patent cover mesna tablets or injections?

Not broadly. The supplied claims focus on granulates. A tablet may fall within a claim only if it contains a granulated mesna composition satisfying all applicable limitations. An injectable solution would ordinarily fall outside these granulate claims.

Does the patent claim mesna's uroprotective use?

No. The supplied claims do not recite preventing urotoxicity, use with ifosfamide, use with cyclophosphamide, or another therapeutic indication.

Is the 0.01-1 binder range in claim 5 broader than claim 1?

Yes. Claim 5 begins at 0.01 parts binder per part mesna, while claim 1 begins at 0.1 parts. Claim 5 is a process claim and includes additional solvent and granulation requirements.

Can the expired patent support a Hatch-Waxman 30-month stay?

No. An expired patent does not provide a current patent basis for a 30-month stay associated with a Paragraph IV certification.

References

United States Patent and Trademark Office. (1993). US Patent No. 5,252,341: Mesna granulate. Washington, DC: U.S. Department of Commerce.
United States Code. (2010). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Silver Spring, MD: U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Listing of patent information in approved drug product labeling. 21 C.F.R. Part 314.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process. Silver Spring, MD: U.S. Department of Health and Human Services.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	4022525	Jul 16, 1990

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	104548	⤷ Start Trial
Australia	638586	⤷ Start Trial
Australia	8044591	⤷ Start Trial
Bulgaria	60851	⤷ Start Trial
Bulgaria	60901	⤷ Start Trial
Canada	2047027	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,252,341

Summary for Patent: 5,252,341