U.S. Patent 5,925,760: Claim Scope, Exclusivity, and Patent Landscape

U.S. Patent No. 5,925,760 is a process and intermediate patent covering the preparation of a protected arginine-piperidine carboxylic acid compound containing a quinolinesulfonyl group. Its broadest product claim covers an N2-quinolinesulfonyl-NG-nitro-L-arginine intermediate. The remaining claims primarily protect specific chemical steps, reagents, stereochemical inputs, and the conversion of the protected intermediate into the tetrahydroquinoline final acid.

The patent is from the pre-Uruguay Round patent-term era and was granted in 1999. Its ordinary 20-year patent term would have expired no later than the late 2010s, subject to the patent’s actual earliest effective nonprovisional filing date and any patent-term adjustment. It is not a currently enforceable U.S. patent under the ordinary term rules in 35 U.S.C. §154(a)(2).

What does U.S. Patent 5,925,760 cover?

The patent covers three related subject-matter groups:

Preparation of N2-(3-substituted-8-quinolinesulfonyl)-NG-nitro-L-arginine.
The protected arginine intermediate itself.
A two-stage process leading to a 3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl arginine-piperidine carboxylic acid.

The claims do not generally claim a pharmaceutical composition, a dosage form, a therapeutic indication, or a broad class of final drug products. The principal legal value is in process control and intermediate protection.

Claim architecture

Claim	Type	Main subject matter	Practical scope
1	Independent process	Condensation of NG-nitro-L-arginine with substituted 8-quinolinesulfonyl chloride	Broad process for making the protected arginine intermediate
2	Independent product	N2-(3-substituted-8-quinolinesulfonyl)-NG-nitro-L-arginine	Broadest composition claim
3	Independent process	Coupling the protected arginine intermediate with a lower alkyl 4-methylpiperidine-2-carboxylate	Protects peptide coupling route
4	Dependent process	Claim 3 using phosphorus oxychloride	Narrows the coupling reagent
5	Dependent process	Claim 3 using ethyl (2R,4R)-4-methylpiperidine-2-carboxylate	Narrows ester and stereochemistry
6	Dependent process	Claims 4 and 5 combined	Specific POCl3-based stereospecific coupling
7	Independent process	Sequential preparation of the protected arginine intermediate and coupling product	Two-step route claim
8	Independent process	Hydrolysis followed by catalytic hydrogenation to the tetrahydroquinoline final acid	Protects final conversion sequence
9	Dependent process	Claim 7 using 3-methyl-8-quinolinesulfonyl chloride and the (2R,4R) ethyl piperidine ester	Specific route to the protected ester
10	Dependent process	Claim 8 using the same defined starting materials	Narrowest final-product process claim

What is the broadest claim in U.S. Patent 5,925,760?

Claim 2 is the broadest claim by subject-matter category because it claims the protected arginine intermediate itself rather than a particular preparation method.

The key structural formula is:

N2-(3-(hydrogen or lower alkyl)-8-quinolinesulfonyl)-NG-nitro-L-arginine.

The claim therefore reaches:

The 3-unsubstituted 8-quinolinesulfonyl species.
The 3-lower-alkyl-substituted species.
The NG-nitro-protected arginine structure.
The N2 sulfonamide linkage between arginine and the quinolinesulfonyl group.

Claim 2 does not, on its face, cover every quinolinesulfonyl arginine derivative. It requires the particular N2 sulfonylation pattern and the NG-nitro protecting group. It also does not expressly claim the later tetrahydroquinoline-piperidine carboxylic acid product.

Scope of the “lower alkyl” language

“Lower alkyl” is a claim-construction issue. In the absence of a limiting definition in the specification, the term ordinarily covers relatively short saturated acyclic alkyl groups, commonly methyl, ethyl, propyl and butyl, although the precise construction depends on the patent’s specification and prosecution history.

The claims expressly identify 3-methyl-8-quinolinesulfonyl chloride in claims 9 and 10. Those claims provide the clearest commercial embodiment.

Which chemical transformations are protected?

Sulfonylation of NG-nitro-L-arginine

Claim 1 protects condensation between:

NG-nitro-L-arginine; and
3-(hydrogen or lower alkyl)-8-quinolinesulfonyl chloride.

This is a reagent-defined process claim. Literal infringement would generally require use of the specified starting materials and the claimed condensation operation. A route using a preformed sulfonamide intermediate could avoid claim 1, although it might remain relevant to claim 2 if the resulting intermediate is made or used in the United States.

Coupling with substituted piperidine carboxylate

Claim 3 protects condensation of the sulfonylated, nitro-protected arginine intermediate with a lower alkyl ester of 4-methylpiperidine-2-carboxylic acid.

The claim covers the esterified coupling product, not merely a generic peptide-coupling concept. Claim 5 narrows the piperidine component to the ethyl ester with (2R,4R) stereochemistry.

The stereochemical limitation is commercially important. A process using a different piperidine stereoisomer would not literally satisfy claim 5 or claim 6, although it could still raise issues under broader claims or the doctrine of equivalents.

Phosphorus oxychloride process

Claim 4 requires the presence of phosphorus oxychloride. Claim 6 adds the specific (2R,4R) ethyl piperidine ester.

These claims are narrower than claim 3 but may have been drafted to capture the preferred manufacturing route. They are vulnerable to process design-around using alternative coupling reagents, activation systems, solvents, or reaction sequences.

Hydrolysis and catalytic hydrogenation

Claim 8 protects a sequence involving:

Hydrolysis of the lower alkyl ester; and
Catalytic hydrogenation of the resulting hydrolysate.

The stated endpoint is the (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine-carboxylic acid.

This claim is directed to a route that both removes the ester and reduces the quinoline ring to the 1,2,3,4-tetrahydro form. A process that performs hydrogenation before hydrolysis, or uses a different reduction sequence, would require separate analysis against the claim language and equivalents.

Does the patent claim the final active pharmaceutical ingredient?

The claims do not present a broad standalone composition claim to the final tetrahydroquinoline-piperidine carboxylic acid. Claim 8 claims a method for making that compound. Claims 9 and 10 further narrow the starting materials and route.

This distinction matters:

A product claim can generally be infringed by making, using, selling, offering to sell, or importing the claimed product.
A process claim is ordinarily infringed by practicing the claimed process, or by importing a product made by the patented process under the applicable statutory rules.
A process patent does not automatically block manufacture through every alternative route.

Claim 2 is the principal product claim, but it concerns the protected arginine intermediate rather than the final tetrahydroquinoline compound.

How strong is the patent estate?

Claim-strength assessment

Claim group	Relative strength	Main reason
Claim 2 intermediate	High among the issued claims	Product claim does not depend on a manufacturing route
Claim 1 sulfonylation process	Moderate	Requires defined starting materials and condensation
Claim 3 coupling process	Moderate	Covers a broader coupling sequence but remains process-specific
Claims 4 and 6	Low to moderate	Narrow POCl3 limitation creates design-around options
Claim 7 sequential process	Moderate	Captures the overall order of intermediate preparation and coupling
Claim 8 final conversion	Moderate	Covers hydrolysis followed by catalytic hydrogenation
Claims 9 and 10	Narrow	Specific reagents, stereochemistry and starting materials

The patent’s historical strength was likely concentrated in process control and access to the protected intermediate. Its present commercial blocking power is limited by expiration and by the availability of alternative synthetic routes.

Main validity pressure points

The claims would have faced several conventional validity and enforcement issues:

Earlier disclosure of N2-protected arginine sulfonamides.
Earlier peptide coupling methods involving substituted piperidine carboxylates.
Obviousness based on known sulfonylation and coupling reactions.
Enablement across the full “hydrogen or lower alkyl” genus.
Written-description support for all claimed substituents and stereochemical combinations.
Claim clarity concerning the relationship between the aromatic 3-methyl-8-quinolinesulfonyl group and the hydrogenated tetrahydroquinoline product.

The broad genus in claims 1 and 2 is materially wider than the specifically identified 3-methyl embodiment. The narrower claims would have provided fallback positions if the genus claims were challenged.

When did U.S. Patent 5,925,760 lose exclusivity?

The patent was granted on July 20, 1999. Under the modern patent-term statute, the relevant expiration date is generally 20 years from the earliest effective U.S. nonprovisional filing date, not 20 years from grant. The patent therefore expired during the late 2010s under the ordinary term framework, absent an unusual patent-term adjustment or other record-specific issue. [1][2]

The patent’s expiration eliminates ordinary infringement liability for conduct occurring after expiration. It does not eliminate:

Liability for pre-expiration conduct.
Contractual obligations under a private license or settlement.
Regulatory exclusivity that may have existed independently.
Trade-secret protection for manufacturing information not disclosed in the patent.

What is the Orange Book status of this patent?

The claims are process and intermediate claims. They do not clearly claim:

A drug substance composition.
A finished dosage form.
A drug formulation.
A method of treating a disease.

For that reason, the patent would not ordinarily be the type of patent listed in the FDA Orange Book as a drug-substance, drug-product, or method-of-use patent. FDA Orange Book listing depends on the approved NDA product and the statutory listing categories, not on patent ownership alone. [3]

A Paragraph IV certification would be relevant only if the patent were listed against an approved drug and an ANDA applicant were challenging that listing. The claim text supplied does not establish such a listing, an approved product, or a Paragraph IV dispute.

Are biosimilar or generic risks relevant?

Biosimilar risk is not relevant. The claimed chemistry concerns a small-molecule peptide-like compound, not a biologic subject to the Public Health Service Act biosimilar pathway.

Generic risk would have been relevant only if the final compound had an approved small-molecule product and the patent had remained enforceable during the generic filing period. The process claims could have created a manufacturing-route risk, but they would not necessarily prevent an ANDA applicant from using a noninfringing alternative process.

Because the patent has expired under the ordinary term framework, it does not currently create a live U.S. patent barrier to generic manufacture.

What patent landscape surrounds the claimed technology?

The relevant landscape should be divided into four layers.

Core compound patents

These would claim the final tetrahydroquinoline arginine-piperidine carboxylic acid, its salts, solvates, stereoisomers, or pharmaceutical compositions. Such patents would present greater product-level risk than U.S. Patent 5,925,760.

Intermediate patents

U.S. Patent 5,925,760 falls principally into this category through claim 2. Intermediate patents can constrain supply chains when a specific protected intermediate is commercially necessary, but they are weaker where manufacturers can purchase or synthesize an alternative intermediate.

Process patents

Claims 1 and 3 through 10 are process claims. Competing manufacturers can reduce exposure by:

Purchasing the intermediate from a lawful source.
Changing the order of sulfonylation and coupling.
Using a different arginine protecting group.
Replacing phosphorus oxychloride.
Using a different ester-removal sequence.
Hydrogenating before hydrolysis.
Employing a different catalyst or reduction system.
Avoiding the claimed 3-methyl quinoline starting material until a later stage.

Formulation and method-of-use patents

No formulation or therapeutic-use claim appears in the supplied claim set. Any commercial exclusivity for the final product would therefore have to come from separate patents, regulatory exclusivity, or trade-secret manufacturing information.

Which companies challenged this patent?

The supplied claim text does not establish any Paragraph IV challenger, ANDA litigation, district-court case, Federal Circuit appeal, or settlement agreement involving U.S. Patent 5,925,760. A defensible litigation conclusion cannot be drawn from the claims alone.

The patent’s age and process-focused claim set make historical prosecution and validity records more relevant than current Hatch-Waxman litigation. Any current generic-launch analysis should treat this patent as expired and focus on later patents covering the final compound, salts, formulations, methods of use, and manufacturing improvements.

Key Takeaways

Claim 2 is the broadest issued product claim and covers a protected quinolinesulfonyl-NG-nitro-L-arginine intermediate.
Claims 1 and 3 through 10 protect specific synthetic operations rather than a broad final drug product.
Claims 5, 6, 9 and 10 narrow the scope through (2R,4R) stereochemistry, the ethyl ester and 3-methyl-8-quinolinesulfonyl chloride.
Claim 8 covers hydrolysis followed by catalytic hydrogenation to the tetrahydroquinoline final acid.
No supplied claim covers a formulation, dosage form, therapeutic indication or broad composition of the final active compound.
Biosimilar analysis is inapplicable because the technology concerns a small molecule.
The patent’s ordinary U.S. term expired in the late 2010s.
The patent is unlikely, based on claim type alone, to be an Orange Book-listed drug-substance, drug-product or method-of-use patent.
Current commercial risk depends on later patents covering the final compound, salts, formulations, uses or alternative manufacturing routes.

FAQs

Does U.S. Patent 5,925,760 cover all methods of making the final compound?

No. The patent claims defined starting materials and reaction sequences. A substantially different noninfringing route may avoid the process claims.

Is the final tetrahydroquinoline compound claimed as a composition?

The supplied claims do not include a broad standalone composition claim to that final compound. Claim 8 is a method claim directed to its preparation.

Can a manufacturer use a different coupling reagent than phosphorus oxychloride?

Claims 4 and 6 specifically require phosphorus oxychloride. A different reagent may avoid those dependent claims, but claim 3 or claim 7 would require separate analysis.

Does the patent protect the (2R,4R) piperidine stereoisomer?

Claims 5, 6, 9 and 10 expressly identify the (2R,4R) ethyl piperidine carboxylate. The broadest claims are less specifically limited by that stereochemical input.

Does patent expiration eliminate regulatory exclusivity?

No. Patent expiration and FDA regulatory exclusivity are separate legal mechanisms. The supplied claims do not identify any applicable FDA exclusivity period.

References

United States Patent and Trademark Office. (1999). U.S. Patent No. 5,925,760.
United States Code. 35 U.S.C. §154(a)(2), patent term.
U.S. Food and Drug Administration. (2024). Approved Drug Products with Therapeutic Equivalence Evaluations, Orange Book.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	8-208087	Aug 07, 1996

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	207482	⤷ Start Trial
Germany	69707603	⤷ Start Trial
European Patent Office	0823430	⤷ Start Trial
Spain	2166937	⤷ Start Trial
Japan	H10101649	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,925,760

Summary for Patent: 5,925,760