United States Patent 6,685,958: Claim Scope, Besifloxacin Coverage, and Patent Landscape

US Patent 6,685,958 covers topical ophthalmic quinolone antibiotic compositions using a broad Markush-defined quinolone, a carboxy-containing polymer, and nonirritating ocular delivery. Its strongest commercial relevance is to besifloxacin ophthalmic products, including Besivance 0.6% ophthalmic suspension. The patent also claims ocular anti-infective methods and a sustained-release ophthalmic delivery system.

The patent is no longer a current U.S. blocking right. Its original term has expired, subject to confirmation of the specific USPTO term-adjustment calculation and any terminal disclaimer. The patent remains important as a historical foundation for the besifloxacin and polymer-based ophthalmic formulation estate, but it should not independently prevent U.S. generic entry today.

What does US Patent 6,685,958 cover?

The patent has three principal claim groups:

Claim group	Claims	Subject matter	Commercial relevance
Composition claims	1-16	Topical ophthalmic quinolone composition containing a carboxy-containing polymer	Core formulation coverage
Treatment claims	17-36	Treating or preventing ocular or periocular bacterial infection	Method-of-use coverage
Delivery-system claim	37	Preparing and packaging a sustained-release topical ophthalmic system	Process and delivery coverage

The central technical combination is:

A quinolone carboxylic acid derivative within a broad chemical formula;
A carboxy-containing polymer, particularly a cross-linked polymer;
Ophthalmic topical administration;
Nonirritation to ocular tissue; and
In selected claims, sustained release.

The patent does not claim every ophthalmic quinolone. It claims compositions and methods that meet the chemical, concentration, polymer, route, and functional limitations recited in the claims.

What quinolone compounds fall within the patent claims?

The formula in claims 1 and 17 is a broad Markush structure. It permits variation at R1, R2, X, Y, and Z. The permitted groups include:

Hydrogen, alkyl, aralkyl, or hydrolyzable ester groups at R1;
Hydrogen or substituted amino groups at R2;
Hydrogen or halogen at X;
CH2, O, S, SO, SO2, or N-R3 at Y; and
Oxygen or a geminal-dihydrogen arrangement at Z.

Claims 9 and 10 narrow the genus to two specific quinolone compounds. Claim 9 identifies:

(R)-(+)-7-(3-amino-2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

This compound corresponds to the besifloxacin structural family. Commercial Besivance contains besifloxacin hydrochloride, formulated as a 0.6% ophthalmic suspension. The patent claim expressly includes the free acid, salts, and hydrochloride form.

Claim 10 covers a related 8-chloro quinolone containing a hexahydro-diazepine-derived substituent. That compound is narrower and distinct from the besifloxacin species in claim 9.

Chemical scope and limitations

The broad formula creates potentially extensive chemical scope, but infringement requires more than structural identity. A product must also satisfy the formulation limitations. For composition claim 1, the product must contain:

About 0.005% to about 10% by weight of the quinolone derivative;
A carboxy-containing polymer; and
A composition that is nonirritating to ocular tissue.

A quinolone product that falls within the chemical genus but lacks the required polymer would not literally meet claim 1. It could still implicate other claims or separate patents, but claim 1 is not a stand-alone compound claim.

What formulations are protected by US 6,685,958?

The formulation claims protect polymer-containing ophthalmic compositions over wide concentration ranges.

Limitation	Claimed range or requirement
Quinolone derivative, claims 1 and 17	About 0.005% to about 10%
Quinolone derivative, claim 6	About 0.02% to 0.25%
Quinolone derivative, method claim 22	About 0.02% to 2.5%
Carboxy-containing polymer, claim 4	About 0.1% to 6.5%
Cross-linked polymer, claim 15	About 0.1% to 6.5%
Cross-linked polymer, claim 16	About 0.5% to 1.0%
Non-carboxyl monoethylenically unsaturated monomers, claim 5	Up to about 40% of the polymer
Hydroxypropyl-beta-cyclodextrin, claim 13	About 5.0% to 20.0%
Dosage forms, claim 33	Solution, composition, ointment, or instillant

The polymer limitation is the principal formulation differentiator. The claims encompass both generic carboxy-containing polymers and cross-linked versions. The specification and commercial context associate this technology with mucoadhesive, sustained-release ophthalmic delivery systems, including polycarbophil-type systems.

The claim language does not require one named polymer in the independent claims. That broad drafting increases coverage but creates claim-construction issues around:

The meaning of “carboxy containing polymer”;
Whether a particular polymer is cross-linked;
The degree of polymer cross-linking;
Whether the polymer materially changes release characteristics; and
Whether the formulation is genuinely nonirritating.

How strong are the independent claims?

Claim 1: composition claim

Claim 1 is the principal composition claim. It is broad in chemical scope but narrower in formulation scope because it requires a carboxy-containing polymer and nonirritation.

Its practical strength is moderate for products that combine:

Besifloxacin or a covered analogue;
A polymeric ophthalmic vehicle;
Concentrations within the stated range; and
A product designed for topical ocular administration.

The “nonirritating” limitation is both commercially sensible and legally significant. It is a functional limitation that may require testing, clinical evidence, or other proof to establish infringement. It also creates potential indefiniteness and enablement arguments if the patent does not provide a sufficiently objective boundary for ocular irritation.

Claim 17: method-of-treatment claim

Claim 17 covers treating or preventing bacterial infection in the ocular or periocular region with the claimed topical composition. It does not require the carboxy-containing polymer in the independent claim, although dependent claim 19 adds that limitation.

The method claim reaches:

Gram-positive infections;
Gram-negative infections;
Mixed infections; and
Ocular or periocular bacterial disease.

Because claim 17 requires the same broad quinolone formula and nonirritating ophthalmic composition, it is not equivalent to a pure method claim covering any use of besifloxacin.

Claim 37: delivery-system preparation claim

Claim 37 covers preparing and packaging a sustained-release topical ophthalmic delivery system. It requires a covered quinolone composition and packaging for ocular administration.

This claim is unusual because the text supplied does not expressly require a carboxy-containing polymer, despite the sustained-release characterization. A patent owner would likely rely on the claim language, specification, and prosecution history to establish what “sustained release” means and whether the composition must contain a release-controlling polymer.

How do the dependent claims narrow the patent scope?

The dependent claims provide several narrower enforcement positions:

Claims 2 and 18 add sustained release.
Claims 4, 15, 16, 20, 31, and 32 specify polymer concentration.
Claims 9, 10, 25, and 26 identify specific quinolone compounds.
Claims 11-13 and 27-29 add a solubilizer, specifically hydroxypropyl-beta-cyclodextrin.
Claims 14-16 and 30-32 require a cross-linked carboxy-containing polymer.
Claims 33-36 define dosage forms and bacterial targets.

Claims 9, 12, 13, 15, and 16 are commercially more focused than claim 1 because they combine identifiable ingredients with quantitative ranges. A generic developer would normally assess these dependent claims against the proposed product composition, not only against the broad independent claim.

Does US 6,685,958 cover Besivance?

Yes, the patent is directly relevant to Besivance because claim 9 identifies besifloxacin-type chemistry and the patent claims polymer-containing ophthalmic delivery. Besivance is a sterile 0.6% besifloxacin hydrochloride ophthalmic suspension indicated for bacterial conjunctivitis.[2]

The relationship is best understood as follows:

Besivance attribute	Relevance to US 6,685,958
Besifloxacin hydrochloride active	Corresponds to claim 9’s hydrochloride coverage
Topical ophthalmic administration	Required by claims 1 and 17
0.6% strength	Falls within the broad 0.005%-10% range
Suspension formulation	Compatible with the claimed composition and dosage-form framework
Polymer-based sustained delivery	Relevant to claims 2, 14-16, 18, and 30-32
Bacterial conjunctivitis indication	Relevant to claims 17 and 34-35

The 0.6% Besivance concentration is outside the narrower 0.02%-0.25% range in claim 6 but remains within claim 1’s broader range. It also falls within the broad concentration language of method claim 17, although not within the specific range recited in method claim 22.

When did US Patent 6,685,958 lose exclusivity?

US Patent 6,685,958 was issued on February 3, 2004.[1] U.S. utility patents filed after June 8, 1995 generally expire 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and applicable priority rules.[3]

The patent’s enforceable term has expired. The expiration date should be treated separately from FDA regulatory exclusivity:

Exclusivity right	Status
US 6,685,958 patent term	Expired
New chemical entity exclusivity	Not applicable to a current launch analysis
Five-year NCE period for besifloxacin	Expired
Pediatric exclusivity	Any six-month period would also have expired
Orange Book patent barrier from this patent	No current patent-term barrier
Biosimilar exclusivity	Not applicable; besifloxacin is a small molecule

Patent expiration does not remove historical relevance. It means that this patent alone should not support a current U.S. patent-infringement injunction against a compliant generic product.

What is the Orange Book status of Besivance?

Besivance is an FDA-approved prescription ophthalmic antibacterial product. The FDA-approved active ingredient is besifloxacin hydrochloride, and the product is associated with Bausch + Lomb.[2]

The Orange Book analysis must distinguish:

The regulatory approval of Besivance;
Listed patents for the reference product;
Expired patents; and
Any later-listed formulation, manufacturing, or crystalline-form patents.

US 6,685,958 may appear in historical patent records associated with Besivance, but its expiration means it is not a current exclusionary asset. A generic applicant would still need to review all currently listed patents and exclusivity codes for the reference listed drug before filing an ANDA.

Were there Paragraph IV challenges or patent litigation?

A Paragraph IV certification is an ANDA applicant’s assertion that a listed patent is invalid, unenforceable, or will not be infringed. The existence of a Paragraph IV notice does not itself establish invalidity or noninfringement.

For US 6,685,958, the relevant commercial question is historical rather than prospective. The patent has expired, so a new Paragraph IV challenge directed solely to this patent would have little practical value. Any historical ANDA litigation must be distinguished from current entry risk because:

The patent may have expired before final litigation resolution;
Later patents may have replaced it as the principal Orange Book barrier;
A settlement may have permitted an authorized or licensed launch; and
Product-specific litigation may have concerned separate formulation or manufacturing patents.

The supplied claim set does not establish a particular Paragraph IV filing, settlement date, consent judgment, or final invalidity ruling. The patent text alone cannot be used to infer those events.

Which companies are challenging the patent estate?

The relevant competitive group includes:

Bausch + Lomb, the Besivance commercial company;
InSite Vision, historically associated with the DuraSite ophthalmic delivery platform;
Generic ophthalmic manufacturers pursuing besifloxacin ANDAs;
Other companies developing noninfringing fluoroquinolone formulations.

No biosimilar companies are relevant because besifloxacin is a chemically synthesized small molecule, not a biologic. Competitive entry would proceed through the ANDA pathway, not the biosimilar pathway under the Public Health Service Act.

A generic company could pursue several design-around strategies:

Design-around route	Potential effect
Use a different nonpolymeric vehicle	Avoids claims requiring a carboxy-containing polymer
Use a polymer outside the claimed composition or concentration	May avoid dependent polymer claims
Use a different quinolone	Avoids besifloxacin-specific species claims but changes product identity
Modify the solubilizer system	May avoid hydroxypropyl-beta-cyclodextrin claims
Use a non-sustained-release formulation	Avoids sustained-release dependent claims
Alter dosage form or delivery mechanism	May avoid claims limited to specific ophthalmic formats

These routes do not eliminate exposure under other patents.

How does this patent compare with the broader besifloxacin patent estate?

US 6,685,958 is a formulation and use patent, not a basic compound patent in the narrow sense. The estate should be divided into four layers:

Estate layer	Typical subject matter	Relevance
Active pharmaceutical ingredient	Besifloxacin molecule, salts, stereochemistry, synthesis	Chemical identity and manufacturing
Formulation	Suspension, polymer vehicle, solubilization, particle characteristics	Product composition
Delivery technology	Sustained release, ocular retention, mucoadhesion	Dosing frequency and residence time
Regulatory listing	Orange Book patents and FDA exclusivity	ANDA timing

The patent is strongest when asserted against a product that reproduces the claimed combination of besifloxacin hydrochloride and a covered carboxy-containing polymer. It is weaker against a product that uses besifloxacin in a materially different vehicle or does not provide the claimed sustained-release characteristics.

What manufacturing and geographic barriers remain?

The patent is a U.S. right. It has no direct force in Europe, Japan, Canada, or other jurisdictions. Foreign equivalents must be evaluated independently for:

Grant status;
National-phase prosecution;
Expiration;
Supplementary protection certificates;
Local claim amendments; and
Litigation history.

Manufacturing risk can remain after composition-patent expiry if a generic relies on:

A patented particle-size distribution;
A protected crystal or salt form;
A proprietary polymer grade;
A sterile manufacturing process;
A preservative system;
A container-closure system; or
A separately patented delivery platform.

US 6,685,958 itself does not create a current U.S. manufacturing barrier once its term has expired. It also does not provide a continuing trade-secret right over the formulation.

What generic launch risks exist after expiration?

The principal current risks are regulatory and technical, rather than infringement risk under this patent.

A generic besifloxacin ophthalmic product would need to address:

Pharmaceutical equivalence;
Strength and dosage form;
Sterility;
Suspension uniformity;
Particle-size distribution;
In vitro release or residence behavior;
Preservative performance, if applicable;
Container compatibility;
Ophthalmic irritation and tolerability;
FDA bioequivalence requirements for the applicable dosage form; and
Any unexpired Orange Book patents.

The expired patent may still influence development because its claims identify the formulation architecture associated with the reference product. A generic can avoid the expired claims but still fail FDA requirements if its vehicle, particle characteristics, or performance differs materially from the reference product.

Key Takeaways

US 6,685,958 covers topical ophthalmic quinolone compositions, ocular treatment methods, and sustained-release delivery preparation.
Claim 9 is directly relevant to besifloxacin hydrochloride.
The core formulation requirement is a carboxy-containing polymer, with dependent claims directed to cross-linked polymers and defined concentrations.
Claims 1 and 17 are broad but contain important chemical and functional limitations.
Claim 37 is a packaging and delivery-system claim with comparatively less explicit polymer detail.
The patent has expired and is not, by itself, a current U.S. barrier to generic entry.
Besifloxacin is a small molecule, so biosimilar analysis is inapplicable.
Current launch diligence should focus on later-listed Besivance patents, FDA requirements, formulation equivalence, and manufacturing patents.
Product-level Besivance revenue is not separately identified in the cited public materials, preventing a reliable revenue-exposure calculation from this patent alone.

FAQs About US Patent 6,685,958 and Besifloxacin

Does US 6,685,958 cover all besifloxacin eye drops?

No. Coverage depends on the complete formulation and claim limitations. Products containing besifloxacin without the claimed polymer or outside applicable dependent-claim limitations may avoid literal infringement of particular claims.

Can a generic launch after US 6,685,958 expires?

Expiration removes this patent as a standalone patent barrier. The generic must still address other listed patents, FDA approval requirements, and any unexpired formulation or manufacturing rights.

Is Besivance protected by a compound patent or a formulation patent?

US 6,685,958 is principally relevant as a composition, delivery, and method-of-use patent. The broader estate may include separate compound, salt, formulation, or manufacturing patents.

Does the patent require sustained release in every claim?

No. Sustained release is expressly added in dependent claims 2 and 18 and is central to claim 37. Independent composition claim 1 and independent method claim 17 do not expressly require sustained release.

Is hydroxypropyl-beta-cyclodextrin required for infringement?

No. It is required only for claims 12, 13, 28, and 29. The independent claims do not require that solubilizer.

References

United States Patent and Trademark Office. (2004). U.S. Patent No. 6,685,958, topical ophthalmic antibiotic compositions.
U.S. Food and Drug Administration. (2009). Besivance (besifloxacin hydrochloride ophthalmic suspension) prescribing information. Bausch & Lomb Incorporated.
United States Code, 35 U.S.C. § 154. Patent term.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	296093	⤷ Start Trial
Australia	2002322002	⤷ Start Trial
Australia	3920300	⤷ Start Trial
Australia	772228	⤷ Start Trial
Canada	2368637	⤷ Start Trial
Canada	2445408	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,685,958

Summary for Patent: 6,685,958