United States Patent 4,382,892: Ofloxacin Scope, Claims, Expiration and Patent Landscape

U.S. Patent No. 4,382,892 covers substituted pyridobenzoxazine quinolone compounds, including ofloxacin, the racemic active ingredient marketed as Floxin. The patent issued May 10, 1983, from a Japanese priority filing and expired under the pre-URAA 17-year-from-issuance rule on May 10, 2000. Its composition claims were broad enough to cover multiple tertiary amino substituents, but claim 8 specifically covers ofloxacin. The patent no longer creates a U.S. blocking right, and current generic entry is not constrained by this patent.

What drug does U.S. Patent 4,382,892 protect?

Claim 8 covers:

9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid

This compound is ofloxacin, a racemic fluoroquinolone antibacterial. Ofloxacin has historically been marketed in oral tablets, oral solution and ophthalmic formulations. The compound has the characteristic fluoroquinolone pharmacophore with:

A fused pyridobenzoxazine ring system;
A fluorine substituent at the 9-position;
A carboxylic acid group;
A ketone at the 7-position;
A methyl substituent at the 3-position;
A 4-methylpiperazinyl substituent at the 10-position.

The patent is a small-molecule composition patent. It does not principally protect a manufacturing process, dosage regimen, pharmaceutical formulation or method of treating a particular infection.

When did U.S. Patent 4,382,892 expire?

Event	Date or status
Earliest priority	1979, based on Japanese priority filings
U.S. filing	Before the 1983 issuance
U.S. patent grant	May 10, 1983
Pre-URAA patent term	17 years from issuance
Base expiration	May 10, 2000
Current status	Expired
Current enforceability	None

The patent was issued before the 1995 change to patent-term calculation. For such patents, the operative term generally ran for 17 years from grant, subject to terminal disclaimers, reexamination adjustments or other specific events. The ordinary expiration date for U.S. Patent 4,382,892 was therefore May 10, 2000.[1]

The patent did not receive the type of Hatch-Waxman patent-term extension commonly available to later-approved drugs. Even if a regulatory extension had been available, the patent term would have remained limited by statutory and regulatory conditions. Public drug-label and Orange Book records do not treat U.S. Patent 4,382,892 as a live patent barrier today.[2]

What are the principal claims of U.S. Patent 4,382,892?

The claims have a layered structure:

Broad genus claim covering a formula with:
- A halogen atom represented by X;
- Hydrogen or C1-C6 alkyl at R;
- A monoalkylamino, dialkylamino or cyclic amino substituent at Z.
A second genus claim that restates and refines the permitted amino substituents.
A narrower subgroup claim covering specified monoalkylamino, dialkylamino and cyclic amino groups.
A species claim with methyl at R and 4-methylpiperazinyl at Z.
A species claim with methyl at R and 4-hydroxypiperazinyl at Z.
A species claim with methyl at R and 3-hydroxypyrrolidinyl at Z.
A species claim with methyl at R and homopiperazinyl at Z.
A specific claim to ofloxacin.

The claim hierarchy is significant. Claims 1 and 2 are Markush claims. They attempt to cover a chemical genus defined by permitted substituent classes. Claims 4 through 8 narrow the genus to identified compounds.

Claim 1: broad amino-substituent genus

Claim 1 covers compounds in which Z is either:

A monoalkylamino group;
A dialkylamino group; or
A cyclic amino group.

The cyclic group list includes azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, homopiperazinyl, thiamorpholinyl and pyrazolidinyl groups. The claim permits further substitution by hydroxyl, C1-C6 alkyl, amino, hydroxyalkyl or mono- or dialkylamino groups.

This is the broadest practical claim in the provided set. It reaches beyond ofloxacin and covers analogues with different ring sizes, heteroatoms and substituents.

Claim 2: revised cyclic-amino genus

Claim 2 contains a similar structure but expressly lists piperazinyl in addition to the other cyclic groups. The supplied claim text for claim 1 contains a duplicated "piperidinyl" reference, while claim 2 contains the expected piperazinyl category. That drafting inconsistency does not change the scope of claim 8, which independently identifies ofloxacin.

Claim 3: selected amino groups

Claim 3 narrows Z to selected monoalkylamino, dialkylamino and cyclic amino groups, including:

Monoethylamino;
Monomethylamino;
Diethylamino;
Dimethylamino;
Azetidinyl;
Pyrrolidinyl;
Piperidinyl;
Morpholinyl;
Piperazinyl; and
Homopiperazinyl.

The claim also limits the cyclic substituent to a 4- to 7-membered ring.

Claims 4 through 7: named analogues

Claims 4 through 7 cover specific methyl-substituted analogues:

Claim	R group	Z group
4	Methyl	4-methyl-1-piperazinyl
5	Methyl	4-hydroxy-1-piperazinyl
6	Methyl	3-hydroxy-1-pyrrolidinyl
7	Methyl	Homopiperazinyl

These claims are narrower than the genus claims and would normally provide fallback positions if a broader Markush claim were challenged.

Claim 8: ofloxacin

Claim 8 is a direct species claim to ofloxacin. It does not depend on proving that a commercial formulation, dosage, salt or treatment method falls within a broader genus. A product containing the claimed active compound would have been directly relevant to claim 8 during the patent term.

How broad is the chemical scope?

The patent’s chemical scope is broader than ofloxacin alone. The central protected class is a substituted pyridobenzoxazine carboxylic-acid scaffold with variable amino substituents.

The main scope variables are:

Variable	Claimed options
X	Halogen
R	Hydrogen or C1-C6 alkyl
Z	Acyclic or cyclic amino substituent
Acyclic Z	Monoalkylamino or dialkylamino
Cyclic Z	Multiple nitrogen-, oxygen- or sulfur-containing rings
Further substitution	Hydroxyl, alkyl, amino, hydroxyalkyl or dialkylamino

The broad genus claims could reach compounds that differ from ofloxacin in the ring substituent, the N-substituent, the halogen identity or the degree of amino-group substitution. The scope is therefore a platform claim set for a class of quinolone antibacterials rather than a single-product claim set.

The practical limitation is that chemical genus claims must be supported by the specification and satisfy written-description, enablement, definiteness and claim-construction requirements. The breadth of a Markush claim does not automatically mean that every structurally remote compound is enforceably covered.

What formulation patents protect ofloxacin products?

U.S. Patent 4,382,892 is not a formulation patent. Its claims are directed to chemical compounds.

Ofloxacin products have been supplied in multiple dosage forms, including:

Immediate-release oral tablets;
Oral liquid formulations;
Ophthalmic solutions;
Ophthalmic ointments or related topical products in certain markets.

A formulation patent would generally require claims directed to excipient combinations, particle characteristics, pH, concentration, container systems, delivery devices or manufacturing steps. Those limitations do not appear in the supplied claims.

The patent therefore would not, by itself, establish exclusivity over every formulation of ofloxacin. It covered the active compound, including the named ofloxacin species, rather than a particular tablet or ophthalmic composition.

What method-of-use patents protect ofloxacin?

The supplied claims contain no method-of-use claims. They do not recite:

Treating a bacterial infection;
Treating a particular organism;
Treating a urinary, respiratory, skin or ophthalmic infection;
A dosage regimen;
A duration of treatment; or
A patient population.

Any method-of-use protection would have had to arise from a separate patent or patent family. Such claims would also have been subject to separate listing and expiration analysis under the Hatch-Waxman framework.

Ofloxacin’s principal regulatory indications included susceptible bacterial infections and ophthalmic infections. FDA labeling is not itself a patent right. Approval for an indication does not extend the term of a compound patent.[3]

What was the FDA and Orange Book status?

Ofloxacin was approved in the United States under the NDA for Floxin and later appeared in generic products. FDA records distinguish between the approved drug, listed patents and regulatory exclusivity.

Regulatory issue	Status
Active ingredient	Ofloxacin
Drug class	Fluoroquinolone antibacterial
Original innovator	Daiichi Pharmaceutical Co., Ltd.
U.S. product	Floxin
Dosage forms	Oral and ophthalmic products
Approval pathway for generics	Abbreviated New Drug Application
U.S. Patent 4,382,892	Expired
Current Orange Book blocking effect	None

The Orange Book may list patents for an approved product at particular points in time, but a historical listing does not preserve patent enforceability after expiration. Generic applicants could rely on an expired compound patent without facing a current patent barrier from U.S. Patent 4,382,892.[2]

The patent’s expiration also means that a current ANDA applicant would not need to make a Paragraph IV certification against this patent. The relevant certification would ordinarily be that the patent had expired, or that no unexpired patent created a barrier.

Were there Paragraph IV challenges and generic-entry disputes?

Ofloxacin became subject to generic competition after expiration of the original compound patent. The central generic-entry event was therefore expiration-based entry rather than a continuing infringement dispute over U.S. Patent 4,382,892.

A Paragraph IV certification is used when an ANDA applicant asserts that a listed patent is invalid, unenforceable or will not be infringed. Once the patent expired on May 10, 2000, the patent no longer supported a Paragraph IV-based 30-month stay or a continuing injunction against ofloxacin approval.

Available public records identify extensive generic availability for ofloxacin after expiration. The existence of later generic products confirms that the original product patent did not prevent market entry after 2000.[2,4]

No current litigation risk remains under this patent. Historical disputes, if any, must be separated from the present legal status because the patent cannot now be enforced.

Which companies challenged or competed with Floxin?

The commercial field included the innovator Daiichi Pharmaceutical and multiple generic manufacturers that entered after expiration. Generic competition in the United States included companies such as:

Watson Pharmaceuticals;
Teva;
Mylan;
Sandoz;
Roxane and related generic suppliers; and
Other approved ANDA holders.

The exact entrant list varied by dosage form, strength, route of administration and time period. Generic approval records should be reviewed at the product level because oral and ophthalmic ofloxacin products did not necessarily share identical applicants or approval dates.[4]

Competition also came from other fluoroquinolones, including ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin. These products were not necessarily covered by U.S. Patent 4,382,892 because their molecular structures and patent families differ.

How does ofloxacin compare with levofloxacin?

Ofloxacin is a racemic fluoroquinolone. Levofloxacin is the S-enantiomer of ofloxacin and was developed as a separate product with a separate patent position.

Attribute	Ofloxacin	Levofloxacin
Chemical relationship	Racemate	S-enantiomer
Original brand	Floxin	Levaquin
Key patent strategy	Racemic compound patent	Enantiomer and related product patents
U.S. Patent 4,382,892	Specifically covers ofloxacin	Does not automatically cover levofloxacin as such
Market entry	Generic entry after 2000	Later patent and regulatory timeline
Commercial positioning	Earlier fluoroquinolone	Later-generation successor product

A patent to a racemate does not automatically provide the same enforcement position as a patent expressly claiming a purified enantiomer, unless the relevant claim language and legal standards support that result. Levofloxacin therefore required separate patent protection and separate regulatory exclusivity analysis.

What was the geographic coverage?

U.S. Patent 4,382,892 provided rights only in the United States. Its expiration had no direct legal effect on corresponding foreign patents.

Ofloxacin was protected through related national patent filings and foreign counterparts in multiple jurisdictions. Each country required separate analysis of:

Priority claims;
Grant date;
Patent-term rules;
Supplementary protection certificates;
Regulatory extensions;
Opposition or revocation history; and
Local generic-entry provisions.

The U.S. expiration date cannot be applied automatically to Europe, Japan, Canada, China or other markets. In particular, foreign rights could have expired earlier or later depending on local filing, grant and extension rules.

What manufacturing and intellectual-property barriers existed?

During the patent term, a manufacturer of ofloxacin faced two principal risks:

Direct infringement risk from making, using, selling or importing the claimed compound.
Patent-family risk from related process, intermediate, formulation or use patents.

U.S. Patent 4,382,892 itself is not a process patent based on the supplied claims. A non-infringing manufacturing route would not have avoided infringement if the resulting product was the claimed ofloxacin compound. Conversely, expiration of the compound patent did not automatically eliminate separate rights covering a particular process or formulation.

After expiration, the principal barriers shifted from compound exclusivity to:

FDA ANDA approval;
Bioequivalence;
Chemistry, manufacturing and controls documentation;
Facility compliance;
Supply reliability;
Product liability;
Commercial contracting; and
Any surviving formulation or process patents.

For a modern entrant, the expired compound patent is no longer the principal risk. Regulatory execution and market economics are more important.

How strong was the patent estate?

Legal strength during the patent term

The estate had strong product-level coverage because claim 8 directly named ofloxacin. The broad Markush claims could have supported additional analogues and provided an enforcement position beyond the marketed compound.

Its principal strengths were:

Direct species claim to ofloxacin;
Broad chemical genus claims;
Multiple fallback claims;
Coverage of several amino-substituent classes;
Early priority relative to later fluoroquinolone products.

Its principal limitations were:

Dependence of the broad claims on specification support;
Potential claim-construction disputes over the Markush language;
No evident formulation claim in the supplied claims;
No evident method-of-use claim in the supplied claims;
A fixed pre-URAA expiration date.

Current strength

Current enforceability is zero because the patent expired. The patent remains relevant for historical freedom-to-operate analysis, patent-family research and understanding the origin of ofloxacin, but it cannot block a current U.S. generic product.

What generic-launch scenarios existed?

The relevant scenarios were:

Scenario	Consequence
Launch before May 10, 2000 without a license	High infringement risk under claim 8
Paragraph IV challenge before expiration	Potential 30-month stay and litigation risk
Launch after patent expiration	No infringement risk from U.S. Patent 4,382,892
Launch of a different fluoroquinolone	Requires separate patent analysis
Launch of a new formulation	Requires formulation-specific patent and FDA review
Importation of an overseas product	Requires U.S. approval and import compliance

The most commercially important scenario was post-expiration generic entry. Because the patent covered the active compound, a manufacturer could not avoid claim 8 merely by changing excipients, tablet color or packaging during the patent term.

Key Takeaways

U.S. Patent 4,382,892 is the foundational U.S. composition patent for ofloxacin.
Claim 8 specifically covers ofloxacin.
Claims 1 and 2 cover a broader pyridobenzoxazine quinolone genus with variable amino substituents.
Claims 4 through 7 cover additional named analogues.
The patent issued May 10, 1983, and expired May 10, 2000.
The patent is expired and has no current U.S. blocking effect.
The supplied claims do not cover a formulation, manufacturing process or method of treatment.
Generic ofloxacin entry followed expiration rather than depending on a current Paragraph IV dispute against this patent.
Levofloxacin has a separate patent and regulatory history because it is the S-enantiomer of ofloxacin.
Current commercial risk lies in FDA approval, manufacturing compliance, supply economics and any separate surviving patents.

FAQs

Is U.S. Patent 4,382,892 still enforceable?

No. The patent expired on May 10, 2000, based on its 17-year term from issuance.

Does U.S. Patent 4,382,892 cover levofloxacin?

Not expressly. Claim 8 identifies ofloxacin, the racemate. Levofloxacin required separate patent protection and separate claim analysis.

Does the patent cover ofloxacin eye drops?

The patent covers the ofloxacin active compound, not a specific ophthalmic formulation. A separate formulation or use patent would be needed for product-specific coverage.

Could a generic company avoid the patent by changing the tablet formulation?

Not during the patent term if the finished product contained the claimed ofloxacin compound. Changing excipients would not ordinarily avoid a direct compound claim.

Is a Paragraph IV certification still required for this patent?

No current Paragraph IV challenge is required against an expired patent. An ANDA applicant would address the patent as expired rather than as an unexpired patent requiring a validity or noninfringement certification.

References

United States Patent and Trademark Office. (1983). U.S. Patent No. 4,382,892: Pyridobenzoxazine derivatives.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Floxin (ofloxacin) prescribing information.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: Ofloxacin drug products and approval histories.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	55-121540	Sep 02, 1980

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	10282	⤷ Start Trial
Australia	529263	⤷ Start Trial
Australia	7487881	⤷ Start Trial
Bosnia and Herzegovina	97190	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,382,892

Summary for Patent: 4,382,892