US Patent 5,262,169: Mesna Tablet Claims, Patent Scope and Generic Entry Risk

US Patent 5,262,169 covers stable oral mesna dosage forms and solvent-granulation processes using defined excipient classes and weight ratios. The patent issued on November 16, 1993, and its pre-URAA term expired on November 16, 2010. It no longer creates an enforceable US patent barrier to mesna tablets or oral mesna manufacturing processes that fall within its claims. Its historical scope remains relevant for freedom-to-operate analysis, patent prosecution strategy, and interpretation of mesna formulation technology. [1][2]

What does US Patent 5,262,169 protect?

The patent protects two related categories:

Finished oral mesna dosage forms, principally tablets.
Processes for producing stable oral mesna dosage forms through wet granulation with specified organic solvents or solvent-water mixtures.

The central technical problem is mesna stability in oral solid dosage forms. The claims address that problem through a combination of mesna, conventional excipients, defined quantitative ranges, and a granulation process.

Claim group	Claims	Subject matter
Tablet composition	1-4	Mesna tablets with defined binder, disintegrant, lubricant and filler ratios
Process claims	5-10	Granulation, drying, lubrication, compression and coating
Consisting-essentially-of process claims	11-16	Similar processes with narrower transitional language
Consisting-essentially-of tablet claim	17	Mesna tablet composition with defined excipient ratios

The patent does not claim mesna as a chemical compound. It does not claim mesna’s use as a uroprotective agent in general. It claims particular oral dosage-form compositions and manufacturing steps.

What are the key limitations in claim 1?

Claim 1 requires every listed element. A potentially infringing tablet must contain:

Mesna as the active ingredient.
A binding agent selected from polyvinylpyrrolidone, gelatin or microcrystalline cellulose.
A disintegrant selected from starch, cross-linked polyvinylpyrrolidone or bentonite.
A lubricant selected from stearates, talcum or polyglycols.
A filling agent selected from starch, cellulose, lactose, fructose, saccharose, sorbitol, mannitol, calcium phosphate or calcium hydrogen phosphate.
The specified amount of each excipient relative to one part by weight of mesna.

The ratio requirements are:

Component	Required amount per 1 part mesna
Binder	0.01-1 parts by weight
Disintegrant	0.03-0.4 parts by weight
Lubricant	0.01-0.2 parts by weight
Filler	0.1-1 parts by weight

The claim uses “selected from the group consisting of,” which ordinarily limits each component to the listed class members. A formulation using a binder outside the listed group, such as hydroxypropyl cellulose, would present a substantial literal-infringement distinction for the binder limitation, subject to claim construction and equivalents analysis.

The supplied text contains typographical defects, including “0. 1-1” for the filler range. The patent’s issued claims and prosecution history, rather than an OCR or transcription error, control the legal analysis. [1]

How broad are claims 2 through 4?

Claim 2: flavoring, sweetening and aromatizing agents

Claim 2 depends on claim 1 and adds at least one flavoring, sweetening or aromatizing substance. It does not independently cover a formulation lacking all such agents.

Claim 3: mesna concentration

Claim 3 requires a tablet containing 10% to 80% mesna by weight. This limitation narrows claim 1. A tablet outside that concentration range may still fall within claim 1 if it satisfies all of claim 1’s excipient ratios.

The concentration limitation is potentially significant because commercial mesna tablets commonly use high drug loading. A formulation containing 10% to 80% mesna may satisfy claim 3 even if the commercial tablet strength differs from the historical examples.

Claim 4: film-coated tablets

Claim 4 adds a pharmaceutically acceptable film coating. It does not specify coating composition, thickness, release profile or coating process. Conventional film coatings would likely fall within the claim if the underlying tablet meets claim 1.

The claim does not require enteric coating, modified release, taste masking or a particular dissolution profile.

What does claim 17 add through “consisting essentially of”?

Claim 17 covers a tablet “consisting essentially of” mesna and the specified excipient categories and ratios. This transitional phrase is narrower than “comprising” and may exclude additional ingredients that materially affect the basic and novel characteristics of the claimed composition.

The likely basic and novel characteristics are the stable mesna oral dosage form and its defined excipient system. Minor conventional additives, such as colorants or processing aids, may not necessarily avoid the claim. An added component that materially changes stability, dissolution, release or the claimed formulation mechanism could support a noninfringement argument.

Claim 17 is not simply a duplicate of claim 1. It creates a different claim-construction issue:

Claim 1 uses “comprising” and is open-ended.
Claim 17 uses “consisting essentially of” and is partially closed.
Claim 17 may exclude additional ingredients that materially affect the claimed stability characteristics.
Claim 17 does not include claim 3’s 10%-80% mesna limitation.

What formulations are protected by the patent?

The patent’s formulation coverage is ingredient- and ratio-specific rather than dosage-strength-specific.

A formulation is most exposed when it contains the following combination:

Mesna.
Polyvinylpyrrolidone, gelatin or microcrystalline cellulose as binder.
Starch, cross-linked polyvinylpyrrolidone or bentonite as disintegrant.
A listed lubricant.
A listed filler.
The stated ratios relative to mesna.

The following design-around approaches could reduce literal overlap:

Design-around variable	Potential approach
Binder	Use a binder not listed in the claim, such as hydroxypropyl cellulose or a different cellulose derivative
Disintegrant	Use a disintegrant outside the listed group
Lubricant	Use a non-listed lubricant
Filler	Use a filler outside the enumerated group
Ratios	Move one or more components outside the claimed ranges
Dosage form	Use a capsule, liquid, granule or alternative oral delivery system
Process	Use dry granulation, direct compression or another process without the claimed solvent granulation
Solvent	Avoid C1-C4 alcohols, acetone and their mixtures with water in the claimed granulation step

These approaches would require evaluation under the doctrine of equivalents. Changing a single excipient may not eliminate risk if the substitute performs substantially the same function in substantially the same way to achieve substantially the same result. The patent’s expired status makes that historical analysis relevant mainly to damages periods, prosecution history, and analogous claim scope in later patents.

What manufacturing processes do claims 5 through 16 cover?

Claims 5 through 16 impose more detailed process limitations than the tablet claims.

Required process elements

The independent process claims require:

Mesna.
The same four excipient categories and ratio ranges used in claim 1.
Granulation with at least one C1-C4 alcohol, acetone or a mixture of those organic agents with water.
Granulation together with at least part of the filler and at least part of the binder.
Conversion of the granulate into a stable oral dosage form.

The process therefore appears directed to wet granulation using solvents such as ethanol, methanol, propanol, isopropanol, butanol, acetone or aqueous combinations.

Dependent claims add specific operations:

Claim	Added limitation
6, 12	Disintegrant present during granulation
7, 13	Drying the granulate
8, 14	Combining the dried granulate with lubricant
9, 15	Pressing the granulate into tablets
10, 16	Applying a pharmaceutically acceptable coating

Claims 5-10 use “comprising,” while claims 11-16 use “consists essentially of.” The latter group may have a narrower scope concerning additional process steps or materials that materially alter the claimed process.

A direct-compression tablet would generally avoid the specific granulation limitation in claims 5-16, although it could still fall within claims 1, 3, 4 or 17 if the finished composition meets the required elements.

How does the patent compare with method-of-use and active-ingredient patents for mesna?

US Patent 5,262,169 is a formulation and manufacturing patent. It is materially different from patents directed to:

Mesna as a chemical compound.
Mesna synthesis or purification.
Mesna administration for preventing urotoxicity.
Mesna dosing schedules with ifosfamide or cyclophosphamide.
Intravenous mesna formulations.
Combination chemotherapy regimens.
Specific pharmacokinetic or therapeutic methods.

The patent does not require a particular cancer treatment, chemotherapy agent, patient population or dosing schedule. It also does not cover injectable mesna unless the injectable product somehow satisfies the claimed oral dosage-form limitations, which it ordinarily would not.

The patent’s commercial relevance was therefore concentrated in oral mesna products, especially stable tablets and their wet-granulation manufacture.

When did US Patent 5,262,169 lose exclusivity?

The patent expired on November 16, 2010, based on its November 16, 1993 issue date and the 17-year patent term applicable to patents governed by the pre-URAA term rules. [1][2]

Event	Date
US patent issue	November 16, 1993
Statutory term basis	17 years from issue for applicable pre-URAA patent
Expected expiration	November 16, 2010
Current status	Expired
Current enforceability	No prospective enforcement against new US activity

Expiration eliminates the ability to obtain injunctive relief or collect infringement damages for post-expiration activity under this patent. Any historical litigation analysis would require assessment of the alleged infringement dates, applicable statutory limitations, and whether another patent was asserted.

Patent expiration also differs from FDA regulatory exclusivity. The expiration of this patent does not itself determine the approval status of generic mesna products.

What is the Orange Book status of mesna products?

The FDA Orange Book addresses approved drug products, therapeutic equivalence and listed patents associated with approved products. It does not treat an expired formulation patent as a current barrier to approval. [3]

For mesna, regulatory review should distinguish among:

Mesna tablets.
Mesna injection.
Brand products such as Mesnex.
ANDA-approved generic products.
Any listed patents or exclusivity codes associated with the relevant NDA.

US Patent 5,262,169 should not be treated as a live Orange Book obstacle because it expired in 2010. A current generic applicant would ordinarily focus on any still-listed patents associated with the relevant reference-listed drug, current FDA exclusivity, labeling requirements and product-specific bioequivalence obligations.

The patent also does not create biologic or biosimilar risk. Mesna is a small-molecule drug. The relevant competitive pathway is generic substitution through an ANDA, not a biosimilar application under the Public Health Service Act.

Were there Paragraph IV challenges or settlements involving this patent?

No current Paragraph IV risk arises from US Patent 5,262,169 because the patent is expired. A Paragraph IV certification is directed to a listed patent that the applicant asserts is invalid, unenforceable or not infringed. An expired patent cannot provide a continuing post-expiration market exclusion under ordinary Hatch-Waxman analysis. [4]

The patent should not be confused with:

Later patents covering mesna formulations.
Patents listed against a specific mesna NDA.
Patent litigation involving other uroprotective products.
Settlements that may have concerned separate patents or regulatory disputes.

A historical Paragraph IV challenge could have occurred before expiration, but the supplied patent information does not establish a particular ANDA, challenger, district court case, settlement date or launch agreement. The enforceability conclusion for the patent itself is unchanged.

Which companies compete in the mesna market?

The relevant commercial landscape has included:

Bristol-Myers Squibb and its Mesnex brand.
Generic manufacturers supplying mesna tablets or injection.
Contract manufacturers and distributors supplying hospital products.
Manufacturers of alternative uroprotection products or chemotherapy-supportive therapies.

Mesna demand is tied primarily to chemotherapy regimens that create a risk of urothelial toxicity, particularly ifosfamide-based treatment. The tablet and injectable products may have different clinical and commercial uses. The patent’s claims affect only the oral solid-dose segment.

Revenue exposure from this patent is therefore product-specific. A company whose mesna revenue derives from injection would have had limited direct exposure to the patent. A company selling high-dose mesna tablets manufactured by the claimed wet-granulation process would have had greater historical exposure before 2010.

Public company-level revenue attributable specifically to products covered by US Patent 5,262,169 is not established by the patent record. The patent does not provide a basis for assigning current revenue to any patent holder.

How strong was the patent estate for mesna tablets?

The patent was technically focused but commercially meaningful during its term.

Strength factor	Assessment
Active ingredient coverage	Narrow; no claim to mesna itself
Composition coverage	Moderate where all listed excipient classes and ranges are present
Process coverage	Moderate; requires specified solvent granulation
Dosage-form coverage	Focused on oral dosage forms, especially tablets
Formulation flexibility	Limited by closed Markush groups and ratios
Design-around potential	Meaningful through excipient substitution or process changes
Method-of-use coverage	None apparent from the supplied claims
Injectable coverage	None apparent
Current legal strength	None; patent expired

The patent’s strongest historical position would have been against a tablet that copied both the excipient system and the solvent-granulation method. Its weaker positions would have involved direct compression, alternative excipients, non-tablet oral dosage forms, or products outside the claimed ratios.

What generic launch scenarios existed?

Before expiration, the principal generic-launch scenarios were:

A Paragraph IV challenge asserting invalidity, unenforceability or noninfringement.
A Paragraph III certification with launch after patent expiration.
A formulation design-around using different excipients or ratios.
A process design-around using direct compression or dry granulation.
A launch of injectable mesna outside the tablet claims.
A licensed launch or settlement-based entry.

After November 16, 2010, the patent no longer supported delayed generic entry. Current launch risk must instead be evaluated against any later patents, regulatory exclusivity, product-specific approval requirements and manufacturing controls.

What geographic coverage did US Patent 5,262,169 provide?

The patent provided rights only in the United States. It did not automatically protect mesna tablets in Europe, Japan, Canada or other jurisdictions.

A corresponding foreign patent family may have existed, but each jurisdiction required separate examination, maintenance and term analysis. The US expiration date cannot be applied to foreign counterparts. International freedom-to-operate work should examine national family members, legal-status records and any supplementary protection certificates or equivalent extensions.

Key Takeaways

US Patent 5,262,169 covers stable oral mesna tablets and solvent-granulation processes.
Claim 1 requires specific excipient classes and quantitative ratios relative to mesna.
Claims 5-16 require granulation with C1-C4 alcohols, acetone or specified aqueous mixtures.
Claims 3 and 4 add mesna concentration and film-coating limitations.
Claim 17 uses “consisting essentially of,” creating a narrower composition framework than claim 1.
The patent does not claim mesna itself, mesna injections or mesna therapeutic use generally.
The patent expired on November 16, 2010.
It creates no current US patent-based generic-entry barrier.
Mesna is a small molecule, so biosimilar analysis is not applicable.
Current commercial risk depends on later patents, FDA exclusivity, Orange Book listings and product-specific regulatory requirements.

FAQs About US Patent 5,262,169 and Mesna Patent Protection

Does US Patent 5,262,169 cover Mesnex tablets today?

No. The patent expired in 2010. It may explain historical formulation protection for oral mesna tablets, but it does not provide current enforceable US exclusivity.

Can a generic mesna tablet use ethanol during manufacture?

Yes, expiration of the patent removes this patent as a current restriction. Before expiration, ethanol or another C1-C4 alcohol used in the claimed wet-granulation process could have created process-claim risk if the composition and other limitations were also met.

Does the patent cover mesna injection?

No. The claims are directed to tablets and stable oral dosage forms. They do not recite an injectable dosage form or parenteral administration.

Is a mesna capsule outside the patent?

A capsule would generally avoid claims expressly limited to a tablet, but claims 5 and 11 cover conversion into a “stable oral dosage form.” The process analysis therefore depends on the particular claim and manufacturing steps used.

Are mesna patent disputes subject to biosimilar litigation?

No. Mesna is a synthetic small-molecule drug. Any applicable Hatch-Waxman dispute would involve an ANDA and potentially Paragraph III or Paragraph IV certifications, not a biosimilar application.

References

United States Patent and Trademark Office. (1993). US Patent No. 5,262,169, Stable oral dosage forms of mesna and process for their preparation.
United States Code, 35 U.S.C. § 154. Patent term provisions.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). ANDA submissions: Refuse-to-receive standards and Paragraph IV certifications.

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
China	1058337	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,262,169

Summary for Patent: 5,262,169