US Patent 5,696,172: Mesna Injectable Solution Claims, Scope, Expiration, and Patent Landscape

US Patent 5,696,172 protects a specific mesna injectable formulation rather than mesna as a molecule, mesna’s use in chemotherapy, or every injectable mesna product. The independent claim requires four elements: mesna, a complexing agent, a pH adjuster, and a preservative, with the finished solution at pH 7.5 to 8.5. The dependent claims narrow the formulation through quantitative weight-ratio ranges.

The patent’s commercial significance is limited today because the 20-year US patent term would have expired no later than the statutory term measured from the relevant nonprovisional filing date, absent patent-term adjustment or an extension. US Patent 5,696,172 issued on December 9, 1997. Patent term analysis must be based on the application’s effective filing date and any recorded term adjustment, not the issue date.[1][2]

What does US Patent 5,696,172 claim?

The patent claims an injectable mesna solution with a controlled pH and selected excipients.

Claim	Claim type	Required formulation elements	Quantitative limitations
1	Independent composition claim	Mesna, complexing agent, pH adjuster, preservative	Finished solution pH about 7.5 to about 8.5
2	Dependent composition claim	Mesna, sodium EDTA, sodium hydroxide, benzyl alcohol	Broad weight ranges relative to one part mesna
3	Dependent composition claim	Mesna, sodium EDTA, sodium hydroxide, benzyl alcohol	Narrower ranges than claim 2
4	Dependent composition claim	Mesna, sodium EDTA, sodium hydroxide, benzyl alcohol	Narrowest ranges for most components

The claims are composition claims. They do not expressly require a particular mesna concentration, container, route of administration, dosage regimen, indication, manufacturing process, or commercial brand.

What is the scope of independent claim 1?

Claim 1 has five central limitations:

An injectable solution.
Mesna.
A complexing agent.
A pH adjuster.
A preservative.
A pH between about 7.5 and about 8.5.

A competing formulation would face a literal infringement issue only if all required limitations were present in the accused product. A formulation lacking a preservative, for example, would not literally meet claim 1. The same applies to a product outside the claimed pH range, although the meaning of “about” would depend on the specification, prosecution history, analytical method, and technical context.

Claim 1 is broad as to the identity and quantity of the complexing agent, pH adjuster, and preservative. It does not require sodium EDTA, sodium hydroxide, or benzyl alcohol. Those specific ingredients appear only in claims 2 through 4.

How does the pH limitation affect infringement?

The pH limitation is a finished-product limitation. It would ordinarily be assessed using the product’s measured pH under defined test conditions, including temperature, dilution, batch sampling, and analytical method.

A product with a labeled pH of 7.5 to 8.5 would present a stronger literal-infringement case than a product with a nominal pH outside the range. The word “about” creates a fact-specific boundary, not an unlimited tolerance. Courts generally interpret “about” in light of the specification, technical understanding, and prosecution record.

A product adjusted to pH 7.4 or 8.6 cannot be treated as outside the claim automatically. The result would depend on how the patent defines or supports the range and whether the alleged equivalent performs substantially the same function in substantially the same way.

What formulations are protected by claims 2, 3, and 4?

Claims 2 through 4 use weight ratios relative to one part mesna. The claims therefore require formulation-specific comparison rather than simple percentage matching.

Claim 2 formulation range

Claim 2 requires:

About one part by weight mesna.
About 0.00002 to about 2.0 parts sodium EDTA.
About 0.0002 to about 2.0 parts sodium hydroxide.
About 0.001 to about 30.0 parts benzyl alcohol.

Claim 2 is broad. Its benzyl alcohol range is particularly wide, extending from 0.001 to 30 parts per one part mesna. The claim also allows relatively broad quantities of sodium EDTA and sodium hydroxide.

Claim 3 formulation range

Claim 3 narrows the ranges:

About one part mesna.
About 0.0001 to about 1.0 parts sodium EDTA.
About 0.0003 to about 1.7 parts sodium hydroxide.
About 0.01 to about 20.0 parts benzyl alcohol.

A formulation within claim 3 will generally also fall within the corresponding broader ranges of claim 2, assuming the same interpretation of “about.” Claim 3 therefore adds a narrower fallback position rather than an independent technical concept.

Claim 4 formulation range

Claim 4 is the narrowest claim:

One part mesna.
About 0.0002 to about 0.7 parts sodium EDTA.
About 0.0004 to about 1.4 parts sodium hydroxide.
About 0.018 to about 12.0 parts benzyl alcohol.

Claim 4 contains a drafting anomaly. It identifies benzyl alcohol as “the complexing agent,” although benzyl alcohol is listed in the formulation as the preservative and sodium EDTA is the complexing agent. The dependency structure and chemical identities strongly indicate that the final phrase should read “the preservative.” The error could create an issue under definiteness or claim construction, but it does not automatically eliminate the claim. Courts may interpret an obvious drafting error when the correction is apparent and does not require guesswork.

How do the dependent claims change the infringement analysis?

The dependent claims add mandatory ingredient and quantity limitations. An accused product must satisfy every limitation of the underlying claim and the dependent claim.

Potential product characteristic	Claim 1	Claims 2-4
Mesna injectable solution	Required	Required
pH 7.5-8.5, approximately	Required	Required through dependency
Any complexing agent	Permitted	No, sodium EDTA required
Any pH adjuster	Permitted	No, sodium hydroxide required
Any preservative	Permitted	No, benzyl alcohol required
Specified quantitative ranges	No	Required
Specific mesna concentration	Not expressly required	Not expressly required, but ratios apply

The patent therefore has a layered claim structure. Claim 1 reaches a wider class of mesna injectable formulations. Claims 2 through 4 provide narrower positions directed to a particular excipient system.

Does the patent cover mesna itself or mesna use in chemotherapy?

No. The claims do not cover mesna as a chemical compound in all forms. They also do not claim:

Mesna tablets.
Mesna oral solutions.
Mesna used to prevent ifosfamide-induced urotoxicity.
A dosing regimen.
Combination therapy with ifosfamide or cyclophosphamide.
Mesna manufacturing intermediates.
Mesna synthesis.
A specific vial, syringe, ampule, or infusion bag.
A particular commercial brand.

The protected subject matter is the claimed injectable formulation. A product containing mesna but lacking the claimed excipient system or pH could fall outside the literal scope.

What is the patent expiration date for US Patent 5,696,172?

The patent’s enforceability depends on its effective filing date, patent-term adjustment, terminal disclaimer, and any applicable patent-term extension. Under the post-URAA framework, utility patents generally expire 20 years from the earliest effective nonprovisional US filing date, subject to statutory adjustments.[2]

The patent issued in 1997. Its issue date did not establish a 17-year term from issuance because the application was governed by the post-1995 patent-term regime. On the available patent record, the patent would have reached its ordinary expiration in the 2010s, not in the 2020s. Any patent-term adjustment would have to be confirmed in the USPTO patent record.[1][2]

The practical conclusion is that US Patent 5,696,172 is not a current blocking patent for US mesna injectable products. Its claims may remain relevant to historical freedom-to-operate analyses, prior-art studies, and prosecution strategy, but they do not create a present US exclusivity barrier after expiration.

What is the Orange Book status of US Patent 5,696,172?

The patent number alone does not establish an Orange Book listing. FDA Orange Book listings are tied to an approved drug application and a patent submitted by the NDA holder or patent owner under the applicable regulatory framework.[3]

US Patent 5,696,172 is a formulation patent, so it could have been relevant to an injectable mesna NDA if the NDA holder submitted it and certified that the patent met Orange Book listing requirements. Its expiration would remove any remaining patent-based delay mechanism even if it had historically appeared in an Orange Book record.

The Orange Book consequences are separate from patent validity:

A patent can be valid but not Orange Book-listed.
A listed patent can expire without invalidation.
An expired patent cannot support a new 30-month stay.
An expired formulation patent does not prevent FDA approval of a therapeutically equivalent product if the product satisfies the applicable approval requirements.

Were Paragraph IV challenges or generic litigation associated with this patent?

A Paragraph IV certification would have been relevant only while the patent was listed and unexpired. A generic applicant could certify that the patent was invalid, unenforceable, or would not be infringed by the proposed product.[4]

The claims supplied do not establish whether a Paragraph IV certification was filed, whether an NDA holder sued, or whether litigation produced a settlement. Those issues require a separate review of FDA Orange Book records, Abbreviated New Drug Application litigation, district court dockets, and Federal Circuit decisions.

The patent’s expiration independently eliminates the forward-looking litigation risk associated with these claims. A historical litigation review could still matter for understanding claim construction, validity positions, or settlement restrictions.

What patent landscape surrounds mesna injectable products?

The relevant landscape has several distinct layers.

Formulation patents

These cover:

pH-controlled mesna solutions.
Preservative systems.
Chelating or complexing agents.
Stability improvements.
Container compatibility.
Multidose injectable presentations.

US Patent 5,696,172 is concentrated in this category. Its strongest technical distinction is the combination of mesna, a complexing agent, a pH adjuster, and a preservative within a defined pH window.

Method-of-use patents

Method-of-use claims could cover mesna administration for prevention of urothelial toxicity during oxazaphosphorine chemotherapy. Those claims are legally distinct from the composition claims in US Patent 5,696,172. An expired formulation patent does not determine whether a separate method patent ever existed or when it expired.

Manufacturing and process patents

Process patents may address:

Control of oxidation or degradation.
Removal of metal ions.
Sterile filtration.
Aseptic filling.
pH adjustment sequence.
Stability during storage.
Container closure systems.

Claim 1 does not require any manufacturing step. A process patent would have to be analyzed independently.

Regulatory and product patents

Mesna products may also implicate:

NDA-specific formulation information.
Pediatric exclusivity.
Orphan-drug exclusivity, if applicable.
Labeling exclusivity.
Device or container patents.
Trade-secret manufacturing controls.

None of those rights can be inferred from the four claims supplied.

How strong is the patent estate for a competing mesna injection?

As an expired patent, US Patent 5,696,172 has no current exclusionary strength in the United States. Historically, its strength would have depended on four factors:

Whether the commercial product fell within pH 7.5 to 8.5.
Whether the product used a preservative.
Whether the formulation used a qualifying complexing agent and pH adjuster.
Whether the quantitative ratios fell within claims 2 through 4.

Claim 1 was broader in ingredient identity but narrower in requiring every functional category. Claims 2 through 4 were narrower because they required sodium EDTA, sodium hydroxide, benzyl alcohol, and specified ranges.

The most practical design-around strategies would have included changing the preservative, eliminating the preservative in a suitable single-dose presentation, using a different pH-adjustment system, replacing sodium EDTA, or formulating outside the claimed pH range. Each strategy would require separate assessment under the doctrine of equivalents and any other unexpired patent rights.

What generic launch risks remain?

The patent-specific generic launch risk from US Patent 5,696,172 is zero after expiration. Remaining launch risks would arise from other sources:

FDA approval requirements for injectable products.
Sterility and particulate specifications.
Product quality and stability.
Manufacturing inspection findings.
Drug-shortage or supply-chain issues.
Unexpired patents outside this patent family.
NDA exclusivity or regulatory exclusivity.
State substitution and reimbursement requirements.
Patent litigation involving other formulation, container, process, or method patents.

A generic mesna injection would not need to avoid US Patent 5,696,172 for a current US launch, but it would still need to establish pharmaceutical equivalence, bioequivalence where applicable, and injectable-product quality under FDA requirements.[3][5]

How does this patent compare with a conventional mesna product patent?

Issue	US Patent 5,696,172	Compound patent	Method-of-use patent
Protected subject matter	Injectable composition	Mesna molecule or chemical entity	Administration or therapeutic use
Required excipients	Yes	Usually no	Usually no
pH limitation	Yes, approximately 7.5-8.5	Usually no	Usually no
Dosage regimen	No	No	Often yes
Manufacturing process	No	No	Sometimes
Design-around potential	Relatively high	Usually low during term	Depends on use and labeling
Current US blocking effect	None after expiration	Depends on expiration	Depends on expiration

Key Takeaways

US Patent 5,696,172 is a formulation patent for an injectable mesna solution.
Claim 1 requires mesna, a complexing agent, a pH adjuster, a preservative, and a finished pH of approximately 7.5 to 8.5.
Claims 2 through 4 require sodium EDTA, sodium hydroxide, and benzyl alcohol in progressively narrower weight-ratio ranges.
The claims do not cover mesna generally, mesna tablets, chemotherapy use, dosing regimens, or mesna manufacturing.
Claim 4 contains an apparent drafting error identifying benzyl alcohol as the complexing agent.
The patent’s ordinary US term expired in the 2010s under the post-URAA 20-year framework, subject to any recorded patent-term adjustment.
The patent does not create a current US generic-entry barrier.
Any present mesna patent risk would have to arise from separate unexpired formulation, process, container, method-of-use, or regulatory rights.

FAQs

Does US Patent 5,696,172 cover single-dose mesna vials?

Not categorically. The claims require an injectable solution with a preservative, but they do not specify a vial, ampule, or multidose container. A single-dose vial could fall within the claims if it contains all required components and satisfies the pH and, for claims 2 through 4, quantitative limitations.

Can a mesna injection avoid the patent by using a different preservative?

A different preservative would generally avoid literal infringement of claims 2 through 4 because those claims require benzyl alcohol. Claim 1 is broader and does not specify the preservative identity, so a different preservative could still fall within claim 1.

Does changing sodium hydroxide to another base avoid claims 2 through 4?

Usually, it would avoid literal infringement of claims 2 through 4 because those claims require sodium hydroxide. Claim 1 does not limit the pH adjuster to sodium hydroxide, so the broader claim would require separate analysis.

Is a mesna product at pH 7.4 outside the patent?

Not automatically. A pH of 7.4 is outside the numerical center of the stated range, but the claim uses “about.” The scope would depend on intrinsic evidence, technical measurement conditions, prosecution history, and potential equivalents. The patent’s expiration is now the controlling practical issue in the United States.

Does patent expiration eliminate FDA approval requirements for generic mesna injection?

No. Expiration removes the patent exclusion but does not waive FDA requirements for pharmaceutical quality, sterility, manufacturing controls, labeling, or the applicable ANDA or other approval pathway.

References

United States Patent and Trademark Office. (1997). US Patent No. 5,696,172.
35 U.S.C. § 154. Patent term and patent-term adjustment.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
21 U.S.C. § 355(j). Abbreviated applications and patent certifications.
U.S. Food and Drug Administration. (2023). ANDA submissions: Content and format requirements.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	42 33 842.5	Oct 08, 1992

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	139693	⤷ Start Trial
Australia	4888393	⤷ Start Trial
Australia	667129	⤷ Start Trial
Brazil	9304151	⤷ Start Trial
Canada	2107961	⤷ Start Trial
China	1071114	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,696,172

Summary for Patent: 5,696,172