US Patent 4,990,517: Claim Scope, Expiration, Orange Book Status, and Quinolone Patent Landscape

US Patent 4,990,517 is an expired Bayer quinolone patent covering broad 7-substituted fluoroquinolone and naphthyridone carboxylic-acid compounds, their salts and hydrates, antibacterial compositions, therapeutic use, and animal-growth applications. The patent issued on February 5, 1991, and its 17-year US patent term expired on February 5, 2008, absent a later-recorded terminal adjustment. Its claims do not create a current US exclusionary barrier.

The patent is technically important because it claims a broad chemical genus around bicyclic diamine-substituted quinolones, including four specifically identified compounds. Its commercial relevance depends on whether a later-developed product falls within the genus, whether a later patent separately protects the marketed active ingredient or formulation, and whether the relevant product was approved before or after the patent expired.

What does US Patent 4,990,517 cover?

The patent covers four principal subject-matter categories:

A broad genus of 7-(pyrrolidinyl)-substituted quinolone and naphthyridone carboxylic acids.
Specific bicyclic diamine derivatives.
Pharmaceutical compositions containing the compounds.
Methods for treating bacterial infections and promoting animal growth.

The independent chemical claim is claim 1. Claims 2 and 3 narrow the substituent definitions. Claims 4 through 7 identify specific compounds. Claims 8 through 10 cover compositions, and claims 11 through 14 cover therapeutic and animal-use methods.

The core scaffold is a 4-quinolone or naphthyridone-3-carboxylic acid with a substituted amino group at the 7-position. The claim language permits substantial variation at the quinolone ring, the N-1 position, the carboxylic-acid substituent, and the bicyclic amine.

What chemical structures fall within claim 1?

Claim 1 covers compounds having the following principal elements:

Claim element	Scope
Core	3-quinolone or naphthyridone carboxylic-acid derivative
7-position	Pyrrolidinyl-derived substituent, including bridged diamine systems
X1	Halogen
X2	Hydrogen, amino, alkylamino, dialkylamino, hydroxyl, alkoxy, mercapto, alkylthio, arylthio, or halogen
R1	C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, hydroxyethyl, fluoroethyl, alkoxy, amino, alkylamino, dimethylamino, or optionally fluorinated phenyl
R2	Hydrogen, C1-C4 alkyl, or a substituted dioxolylmethyl group
R3	A substituted diazabicyclic or related nitrogen-containing ring
A	Nitrogen or substituted carbon
Salt and hydrate coverage	Addition products with water, acid, or alkali

The genus is substantially broader than any one commercial compound. It covers positional and substituent variants that differ in ring nitrogen placement, bridge structure, halogenation, N-1 substitution, and salt form.

How do claims 2 and 3 narrow the genus?

Claim 2 reduces the available substituent ranges. It limits X1 principally to fluorine or chlorine, narrows X2, reduces alkyl ranges, and restricts the R3 substituent set.

Claim 3 is narrower still. It limits X1 to fluorine and X2 to hydrogen, amino, methylamino, or fluorine. It also limits R1 to selected small groups, including ethyl, vinyl, cyclopropyl, 2-hydroxyethyl, 2-fluoroethyl, methoxy, methylamino, 4-fluorophenyl, and 2,4-difluorophenyl.

Claim 3 also introduces a Z variable representing oxygen or sulfur. This claim therefore appears directed to a more defined subset of bicyclic amine quinolone structures rather than the full claim 1 genus.

Which specific compounds are claimed?

Claims 4 through 7 identify four compounds. The names in the supplied text are reproduced below with normalization of obvious typographical errors.

Claim	Specific compound
4	1-Cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
5	8-Chloro-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
6	5-Amino-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
7	1-Cyclopropyl-7-(2,7-diazabicyclo[3.3.0]oct-7-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

Each compound is also claimed as an addition product with water, an acid, or an alkali. That language is intended to encompass hydrates, acid-addition salts, and alkaline or basic salts. It does not automatically cover every formulation, polymorph, co-crystal, or prodrug unless the product falls within the chemical definition of the claimed addition product.

What is the scope of the pharmaceutical composition claims?

Claim 8 covers an antibacterial composition containing:

an antibacterially effective amount of a claim 1 compound or addition product; and
a diluent.

Claims 9 and 10 narrow the composition to particular diluents or dosage contexts:

tablets, capsules, or ampules;
animal feed stock.

The composition claims are structurally dependent on the chemical claims. A product must contain a compound within claim 1 or a relevant dependent claim. A composition containing a later-developed quinolone outside the claimed genus would not infringe merely because it is antibacterial or is sold in a tablet.

The formulation coverage is broad but conventional. It does not expressly claim a specific controlled-release matrix, injectable vehicle, particle-size distribution, polymorph, coating, excipient system, or dosage regimen. Those technologies would generally require separate claim elements in a later formulation patent.

What do the method-of-use claims protect?

Claims 11 through 14 cover antibacterial treatment and animal-growth promotion.

Human or patient treatment

Claim 11 covers administering an antibacterially effective amount of a claim 1 compound to a patient in need. The claim is broad as to bacterial disease and does not limit the method to a named pathogen, route of administration, dose, treatment duration, or anatomical site.

Animal-growth promotion

Claim 12 covers administering a growth-promoting amount to an animal. Claims 13 and 14 identify selected compounds for the therapeutic and animal-use claims.

The supplied claim text states that claim 13 depends on claim 15, although no claim 15 appears in the provided set. That is almost certainly a transcription, OCR, or source-text defect. The enforceable scope must be determined from the issued patent and its official prosecution record, not from the malformed transcription alone. The defect does not expand the patent beyond the claims actually issued.

When did US Patent 4,990,517 expire?

US Patent 4,990,517 issued on February 5, 1991. For a US utility patent of this vintage, the ordinary term was 17 years from grant. On that basis, the patent expired on February 5, 2008, subject to any patent-term adjustment or terminal disclaimer recorded in the official file.[1]

Event	Date
Patent issued	February 5, 1991
Ordinary 17-year term from grant	February 5, 2008
Current status	Expired
Current enforceability	No ordinary patent exclusionary right

Because the patent issued before the 1995 change to the US patent-term system, the grant-date rule generally controls rather than the 20-year-from-earliest-effective-filing-date rule.[2]

What is the Orange Book status of US Patent 4,990,517?

US Patent 4,990,517 is not a current Orange Book barrier for an approved drug product. The Orange Book lists patents submitted by a new-drug application holder for an approved product and identifies patent expiration information, including patents covering active ingredients, formulations, and methods of use.[3]

The patent does not appear to function as a current listed patent for a major marketed quinolone product. Its claims are directed to a broad research-era compound genus and include animal-growth uses that would not independently create an Orange Book listing for a human drug.

The absence of a current Orange Book listing matters commercially:

An ANDA applicant would not face a current Paragraph IV challenge directed to this patent.
The patent cannot support a 30-month stay under Hatch-Waxman.
The patent cannot block an ANDA or 505(b)(2) application after expiration.
Any present-day barrier would have to arise from a later unexpired patent, regulatory exclusivity, orphan-drug exclusivity, or a separate formulation, method, manufacturing, or crystal-form patent.

Did this patent create Paragraph IV risk?

During its life, a generic or follow-on applicant could have challenged the patent under Paragraph IV if the patent had been listed against an approved product. Paragraph IV certifications typically assert that the listed patent is invalid, unenforceable, or not infringed.[4]

That risk is now historical. Since US Patent 4,990,517 expired in 2008:

no current Paragraph IV certification can create a 30-month stay based on this patent;
a later applicant need not certify against an expired patent as an operative obstacle;
litigation based solely on this patent would generally lack prospective injunctive value.

The more relevant question for a current product is whether later patents claim the marketed active ingredient in a narrower form. A broad expired genus patent may be important prior art or historical evidence, but it does not substitute for a live product patent.

How strong was the patent estate?

Strengths

The patent had several features that would have supported meaningful protection during its term:

Claim 1 covered a large chemical genus.
The claims included both quinolone and naphthyridone cores.
The permitted N-1 and ring substituents were varied.
The claims expressly included salts and hydrates.
The patent included composition and treatment claims.
Four specific bicyclic amine compounds were separately claimed.

The combination of a broad genus claim and specific compound claims can create multiple infringement routes. A competitor could avoid a specific example yet remain within the genus.

Limitations

The patent also had important limitations:

the term ended in 2008;
the claims did not expressly protect modern formulation technologies;
no specific marketed drug is identified in the supplied claims;
the animal-growth claims have limited modern US commercial relevance;
a broad genus claim can face validity pressure if the specification does not adequately support or enable the full chemical scope;
the claim transcription contains dependency and nomenclature defects.

The practical strength of claim 1 would have depended on written-description and enablement support across the full set of permitted substituents. Under modern US law, genus claims are vulnerable when the specification does not demonstrate possession of, or teach how to make and use, the full claimed genus.[5]

What later patents would matter for a commercial product?

A commercial product potentially falling within US Patent 4,990,517 would need a separate analysis of later patent families. The relevant categories are:

Later patent category	Commercial relevance
Active-ingredient composition of matter	Usually the strongest product protection
Stereochemical or enantiomeric form	Can protect a specific active isomer not expressly isolated in the earlier patent
Salt, hydrate, polymorph, or crystal form	May delay generic substitution if valid and listed
Pharmaceutical formulation	Can protect tablets, suspensions, injectables, or release systems
Method of treatment	Can create skinny-label or induced-infringement issues
Manufacturing process	Can restrict API supply or create process-litigation exposure
Prodrug	Can support a separate product patent and regulatory strategy
Combination therapy	Can protect a defined antibacterial regimen
Veterinary formulation	Relevant to animal-health products rather than human ANDA exposure

The existence of a broad expired genus patent does not establish that a later compound is unpatented. Conversely, a later patent claiming a narrower embodiment does not revive the expired patent or extend its term.

How does the patent compare with later fluoroquinolone estates?

US Patent 4,990,517 is best viewed as an early platform patent rather than a complete commercial-product estate.

Estate type	Typical protection	Relative position versus US 4,990,517
Early quinolone genus patent	Broad chemical genus, salts, uses	Broad but expired
Later active-ingredient patent	Specific molecule, stereochemistry, or substituent pattern	Usually stronger for the marketed product
Formulation patent	Dosage form, excipient system, release profile	Narrower but commercially targeted
Method patent	Infection, dosing regimen, or patient population	Depends on label and prescribing conduct
Process patent	API synthesis or purification	Relevant to suppliers and manufacturing
Regulatory exclusivity	FDA approval-based market protection	Independent of patent validity

The patent’s strongest historical value was its breadth. Its weakest current feature is that all patent rights have expired.

Which companies are challenging this patent?

No current commercial challenge is material because the patent expired in 2008. A live generic challenge would ordinarily be directed to an unexpired Orange Book-listed patent, not to this expired patent.

Historical litigation, prosecution, assignment, and family information should be checked in the USPTO Patent Center record and the relevant district-court or Federal Circuit databases. The supplied material does not establish a current infringement action, settlement agreement, or licensing transaction tied specifically to US Patent 4,990,517. No such transaction should be inferred from the claim text alone.

What is the geographic coverage?

The patent provides US coverage only. Any foreign protection would arise from corresponding national or regional applications, not automatically from the US patent.

A global freedom-to-operate review would normally examine:

the priority application;
European Patent Office family members;
German and other national filings;
Japanese and Canadian counterparts;
patent-term adjustments or extensions;
national lapse, renewal, and opposition records;
later patent families claiming commercial compounds.

Expiration of the US patent does not establish expiration of every foreign counterpart, although most counterpart rights from the same early filing period would also be expired by now.

What generic launch risks remain?

The patent itself creates no current generic launch risk. A present-day launch assessment should focus on five questions:

Whether the active ingredient is approved in the United States.
Whether an unexpired composition-of-matter patent exists.
Whether an Orange Book-listed formulation or method patent remains unexpired.
Whether regulatory exclusivity remains available.
Whether the proposed product uses a patented process, polymorph, salt, or dosage form.

For an old quinolone candidate that was never approved, the main commercial issue may be development economics rather than patent infringement. For an approved product, later product-specific patents would control the launch date.

Key Takeaways

US Patent 4,990,517 covers a broad genus of 7-substituted quinolone and naphthyridone carboxylic acids.
It includes specific bicyclic diamine compounds, salts, hydrates, antibacterial compositions, patient-treatment methods, and animal-growth methods.
The patent issued on February 5, 1991, and its ordinary US term expired on February 5, 2008.
It is not a current Orange Book or Paragraph IV barrier.
The patent’s broad chemical claims were historically significant but do not protect a product today.
Current risk would come from later patents covering a specific active ingredient, stereoisomer, formulation, polymorph, manufacturing process, or method of use.
The supplied claim text contains a defective dependency reference to claim 15; the issued patent and prosecution record control the legally operative text.
No current litigation, settlement, or licensing restriction can be established from the claims alone.

FAQs

Does US Patent 4,990,517 cover ciprofloxacin?

The claim text does not identify ciprofloxacin by name. Whether ciprofloxacin falls within any claim would require structural mapping against each limitation, including the 7-substituent, ring substitution, and R-group definitions. Ciprofloxacin would also be governed by its own patent history and later regulatory records.

Can an expired genus patent block a new quinolone launch?

No. An expired patent cannot support an injunction or prevent commercial launch. It may remain relevant as prior art against later patent applications, but it does not create a current exclusionary right.

Do the claims cover all salts and hydrates of the claimed compounds?

They cover addition products with water, an acid, or an alkali, but the scope depends on whether the particular product is legally an addition product of a claimed compound. The wording does not automatically cover every solid form, co-crystal, formulation, or prodrug.

Could claim 8 cover a modern injectable formulation?

Only if the injectable contains a compound within the underlying chemical claims and satisfies the composition language. Claim 8 does not independently protect every antibacterial injectable formulation.

Is animal-growth-promotion coverage still commercially important?

The animal-use claims are part of the patent’s historical scope, but they do not create current patent rights after expiration. Regulatory restrictions on antibiotic use in food-producing animals also limit the practical value of that claim category.

References

United States Patent and Trademark Office. (1991). US Patent No. 4,990,517, 7-(pyrrolidinyl)-3-quinolone- and -naphthyridone-carboxylic acid derivatives.
United States Code, 35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
United States Code, 21 U.S.C. § 355(j). (2024). Abbreviated applications for new drugs.
United States Code, 35 U.S.C. §§ 112, 271. (2024). Patent specification and infringement.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3824072	Jul 15, 1988
Germany	3906365	Mar 01, 1989

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0350733	⤷ Start Trial	300111	Netherlands	⤷ Start Trial
European Patent Office	0350733	⤷ Start Trial	SPC/GB03/034	United Kingdom	⤷ Start Trial
European Patent Office	0350733	⤷ Start Trial	2001C/030	Belgium	⤷ Start Trial
European Patent Office	0350733	⤷ Start Trial	11/2000	Austria	⤷ Start Trial
European Patent Office	0350733	⤷ Start Trial	C300111	Netherlands	⤷ Start Trial
Austria	135354	⤷ Start Trial
Austria	292127	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,990,517

Summary for Patent: 4,990,517