US Patent 10,632,197: Claim Scope, Validity Risk, and Fluorescein-Benoxinate Patent Landscape

US Patent 10,632,197 protects ophthalmic compositions containing fluorescein and benoxinate within narrow concentration ranges and with a defined low-impurity profile. The patent also covers use of those compositions for foreign-body or suture removal and ocular examinations, including intraocular-pressure measurement. Its commercial value depends primarily on whether the marketed product and any abbreviated new drug application product fall within the impurity limitations, not merely whether they contain fluorescein and benoxinate.

What does US Patent 10,632,197 claim?

The independent claims create three principal coverage categories:

Claim category	Claims	Core limitation
Composition	1	0.20%-0.30% fluorescein, 0.32%-0.48% benoxinate, total impurity of about 1.5% or less
Treatment or diagnostic use	18-20	Administration for foreign-body or suture removal, ocular examination, and intraocular-pressure measurement
Quality and impurity subprofiles	2-15	Total impurity or specified impurities at selected storage-time concentrations and relative retention times

Claim 1 is the commercial center of gravity. It requires:

A fluorescein component at about 0.20%-0.30% by weight.
A benoxinate component at about 0.32%-0.48% by weight.
Total impurities of about 1.5% or less by weight.
One or more impurities having relative retention times from about 0.10 to about 1.90 under HPLC Method A.

The claim does not expressly require a particular container, dose volume, pH, tonicity, route, or ophthalmic dosage form. Those limitations appear only in dependent claim 16 and claim 17, which add inactive agents and preservatives.

How broad is the composition claim?

Claim 1 is narrower than a basic fluorescein-benoxinate combination claim but potentially broad across formulations that use the same active-ingredient concentrations and meet the analytical specification.

Active-ingredient ranges

The claimed ranges cover the common commercial strength of approximately 0.25% fluorescein and 0.4% benoxinate. Those concentrations fall near the center of both claimed ranges:

Ingredient	Claimed range	Representative commercial strength	Position within range
Fluorescein component	0.20%-0.30%	0.25%	Central
Benoxinate component	0.32%-0.48%	0.40%	Central

The use of "about" expands the practical boundary, although the extent of that expansion depends on intrinsic evidence, specification examples, prosecution history, analytical precision, and prior-art practice. A product at 0.30% fluorescein or 0.48% benoxinate may remain within the claim if the court treats "about" as allowing ordinary manufacturing variation.

The claims use "component," rather than expressly limiting the active ingredients to a particular salt or chemical form. A product containing fluorescein sodium and benoxinate hydrochloride would likely present a stronger literal-coverage case than a product using chemically distinct derivatives. The exact interpretation depends on the patent specification and prosecution history.

Impurity limitation

The impurity limitation is the principal narrowing feature. The composition must have total impurity of about 1.5% or less by weight, with the relevant impurities identified by HPLC relative retention time.

This limitation creates two separate questions:

Whether the product meets the quantitative impurity ceiling.
Whether its impurity peaks fall within the relative-retention-time window under HPLC Method A.

A competitor cannot avoid the claim simply by using a different impurity nomenclature if its product produces the claimed HPLC profile. Conversely, a competitor may have a noninfringement position if its analytical method, reference standard, chromatographic conditions, or impurity profile does not satisfy the method-specific limitation.

What do claims 2 through 15 add?

Claims 2 through 15 provide narrower dependent positions around stability and individual impurity peaks. The specified relative retention times are approximately 0.43, 0.68, 0.74, and 0.79.

Claims	Added subject matter	Commercial relevance
2-3	Total impurity levels after 0, 12, or 18 months	Stability profile
4-6	Impurity at relative retention time about 0.43	Specific degradant or process impurity
7-9	Impurity at relative retention time about 0.68	Specific chromatographic impurity
10-12	Impurity at relative retention time about 0.74	Specific chromatographic impurity
13-15	Impurity at relative retention time about 0.79	Specific chromatographic impurity

These claims use long lists of alternative numerical thresholds. They create a descending series from 1.5% to 0.001%, both as exact "about" values and as "less than" values.

The practical effect is limited. A dependent claim is infringed only if the product satisfies the parent claim and the added impurity limitation. The claims do not appear to identify the chemical structures of the impurities. Relative retention time alone may make infringement testing more difficult because retention time is method-dependent and can vary with column chemistry, mobile phase, temperature, flow rate, instrument configuration, and reference compound.

Does the patent cover the marketed fluorescein-benoxinate product?

The patent is directed to the formulation profile associated with fluorescein-benoxinate ophthalmic products, including products commonly supplied at approximately 0.25% fluorescein and 0.4% benoxinate. A product with those active concentrations is a candidate for literal coverage, but concentration matching alone is insufficient.

A potentially infringing product would need to satisfy the following matrix:

Element	Required showing
Fluorescein	About 0.20%-0.30% by weight
Benoxinate	About 0.32%-0.48% by weight
Total impurities	About 1.5% or less by weight
HPLC profile	At least one impurity within the claimed relative-retention-time range under Method A
For method claims	Administration for a claimed ocular purpose
For dependent composition claims	Claimed excipients or preservative, if relied on

The patent does not require boric acid, povidone, purified water, hydrochloric acid, or chlorobutanol in claim 1. Those ingredients appear in claims 16 and 17. A formulation lacking those excipients could still infringe claim 1 if the active and impurity limitations are met.

What is the scope of the method-of-use claims?

Claims 18 and 19 cover administration of the claimed composition for specified ocular purposes.

Claim 18 covers removal of foreign bodies and sutures. Claim 19 covers conducting an ocular examination. Claim 20 narrows claim 19 to an examination that includes measurement of intraocular pressure.

These claims are narrower than a general treatment claim because they require:

The specified fluorescein and benoxinate composition.
A therapeutically effective amount.
Administration to a subject in need.
The claimed clinical purpose.

The method claims may be relevant to physicians, clinics, product labels, and induced-infringement theories. They are less useful against a manufacturer if the product is sold with a label that omits the patented use and the manufacturer does not encourage the claimed activity. The composition claims generally provide the stronger product-side enforcement position.

How strong is the patent estate?

Strengths

The patent has several commercially useful characteristics:

Claim 1 maps to the standard active-ingredient strengths used in fluorescein-benoxinate ophthalmic products.
The impurity ceiling can distinguish the claimed product from older or less stable formulations.
HPLC-defined quality limitations can be difficult to assess from public product labeling.
The claims cover both the formulation and selected clinical uses.
Claims 2-15 provide fallback positions if broader impurity language is challenged.

Weaknesses

The principal vulnerabilities are analytical and claim-construction issues:

HPLC Method A dependency. The scope depends on a named method that must be sufficiently clear and reproducible.
Relative retention time rather than impurity identity. Retention time is not an intrinsic chemical identity and may shift across laboratories.
Unidentified impurities. The claims do not expressly identify the chemical structures corresponding to the peaks at 0.43, 0.68, 0.74, or 0.79.
"About" language. The boundaries of the active ranges and impurity thresholds may be contested.
Storage-time limitations. Claims 2-15 refer to 0, 12, or 18 months, creating questions about the required testing date and whether the claim covers release specifications, shelf-life specifications, or both.
Potential overlap among dependent claims. The extensive numerical alternatives may create redundancy without materially expanding enforceable scope.
Prior-art product risk. If an earlier fluorescein-benoxinate product had the claimed concentrations and impurity profile, the patent could face anticipation or obviousness attacks.

The strongest claims are likely claim 1 and the narrower impurity-specific claims that can be supported by reproducible testing. Claims 18-20 have narrower commercial reach but may support enforcement against use-specific labeling.

When does US Patent 10,632,197 lose exclusivity?

The patent grant date was April 28, 2020. Patent expiration cannot be reliably calculated from the claim text alone because the term depends on the earliest effective nonprovisional filing date, any terminal disclaimer, patent-term adjustment, patent-term extension, and relevant priority chain. Under 35 U.S.C. § 154, a U.S. utility patent generally has a 20-year term measured from the effective filing date, subject to adjustments and disclaimers.

The patent’s grant date does not establish its expiration date. A commercial exclusivity analysis must distinguish:

Exclusivity type	Relevance
Patent term	Controlled by filing history and USPTO term calculation
FDA drug exclusivity	Controlled by the NDA approval and statutory exclusivity period
Orange Book listing	Determines whether an ANDA applicant must address the patent
Patent-term extension	May extend eligible FDA-regulated product patents
Terminal disclaimer	May shorten the term to an earlier patent’s expiration

What is the FDA and Orange Book significance?

A composition patent may be listed in the Orange Book if it claims the approved drug substance, drug product, or method of use and satisfies FDA listing requirements. FDA Orange Book listings are product-specific and tied to an NDA, dosage form, route, and approved labeling. The existence of US Patent 10,632,197 does not by itself establish that the patent is listed for every fluorescein-benoxinate product.

For an ANDA applicant, the relevant questions are:

Whether the reference listed drug has an Orange Book listing for this patent.
Whether the patent is listed for the specific ophthalmic solution.
Whether the applicant makes a Paragraph III certification or Paragraph IV certification.
Whether the NDA holder files suit within 45 days after receiving a Paragraph IV notice.
Whether a 30-month stay applies under 21 U.S.C. § 355(j)(5)(B)(iii).

Because the claims are product-quality and method-of-use claims, the patent may create a Paragraph IV issue if it is listed against the reference product. If it is not listed, the applicant may still face ordinary patent litigation, but the statutory ANDA stay mechanism may not apply.

What Paragraph IV challenges and generic-entry risks exist?

A generic applicant targeting a fluorescein-benoxinate ophthalmic solution could use several strategies:

Certification strategy

If the patent is Orange Book-listed, an applicant could:

File Paragraph III and wait for patent expiration.
File Paragraph IV and challenge validity, enforceability, or infringement.
Submit a section viii statement for a method-of-use claim if the patented use can be carved out.
Seek a label that omits the claimed suture-removal, foreign-body-removal, or intraocular-pressure-measurement use.

Noninfringement strategy

The principal technical arguments would target:

Fluorescein or benoxinate concentration outside the "about" ranges.
Total impurities above 1.5%.
No impurity within the specified HPLC retention-time range.
Use of a validated method that does not correspond to HPLC Method A.
A different impurity profile caused by manufacturing, raw materials, or storage.
A label that does not encourage the claimed methods.

The most difficult design-around would be maintaining the same active concentrations while reliably avoiding the total-impurity and relative-retention-time limitations. A small formulation change may not be enough if the resulting product continues to meet the claimed analytical profile.

Are biosimilars relevant to this patent?

No. Fluorescein and benoxinate are small-molecule active ingredients, not biologics. The relevant competitive pathway is an ANDA under section 505(j), not a biosimilar application under section 351(k). Biosimilar interchangeability, reference-product exclusivity, and biologic patent dance procedures do not apply.

Which companies are likely to be affected?

The principal affected parties are the NDA holder, manufacturers of fluorescein-benoxinate ophthalmic solutions, contract manufacturers, and ANDA applicants seeking approval for the same strength and dosage form. The product commonly associated with this combination is Fluress, an ophthalmic solution containing fluorescein sodium and benoxinate hydrochloride. FDA product records and current Orange Book entries control the legal relevance of the patent to that product. [FDA, n.d.-a; FDA, n.d.-b]

No conclusion about a particular company’s infringement, Paragraph IV filing, settlement, or litigation status follows from the claim text alone. Those conclusions require the current USPTO assignment and maintenance records, FDA listing data, court dockets, and any ANDA notice letters.

What manufacturing and IP barriers does the patent create?

The patent’s practical barrier is process control rather than molecule ownership. A competing manufacturer must control:

Raw-material impurity content.
Fluorescein and benoxinate assay levels.
Degradation during sterilization and filling.
Container-closure compatibility.
Preservative stability.
HPLC method reproducibility.
Shelf-life impurity growth at 12 and 18 months.

A manufacturer may produce a chemically equivalent product but still face a patent issue if its impurity profile falls within the claimed ranges. Conversely, avoiding the claims may require a process or formulation that changes stability, preservative performance, pH, or regulatory comparability.

Key Takeaways

US Patent 10,632,197 is primarily a formulation-quality patent, not a basic fluorescein or benoxinate composition-of-matter patent.
Claim 1 targets approximately 0.25% fluorescein and 0.4% benoxinate with total impurities of about 1.5% or less.
Claims 2-15 narrow the estate around storage-time impurity thresholds and peaks at relative retention times of approximately 0.43, 0.68, 0.74, and 0.79.
Claims 18-20 cover foreign-body and suture removal, ocular examination, and intraocular-pressure measurement.
The central validity and infringement issues are HPLC Method A, retention-time reproducibility, the meaning of "about," and whether the claimed impurity profile was present in prior commercial products.
Generic risk depends on Orange Book listing, ANDA certification strategy, product testing, and the scope of the approved label.
Biosimilar analysis is irrelevant because the active ingredients are small molecules.
The patent’s exact expiration date cannot be established from the claims; the effective filing date, PTA, PTE, and any terminal disclaimer control.

FAQs

Does US Patent 10,632,197 claim fluorescein sodium by itself?

No. The independent composition claim requires both a fluorescein component and a benoxinate component within specified concentration ranges, together with the impurity limitation.

Can a generic avoid the patent by changing chlorobutanol?

Potentially, but only if the generic does not satisfy the independent claim. Chlorobutanol appears in dependent claim 17 and is not required by claim 1. Changing the preservative alone may therefore leave the generic within claim 1.

Does a product with 0.25% fluorescein and 0.4% benoxinate automatically infringe?

No. It must also satisfy the total-impurity and HPLC relative-retention-time limitations. The active concentrations are necessary but not sufficient.

Can an ANDA applicant omit the patented ocular uses?

A section viii carve-out may reduce risk for method-of-use claims if FDA permits the labeling omission and the remaining label does not encourage the patented uses. A carve-out does not eliminate exposure under an independently enforceable composition claim.

Is the patent likely to block all fluorescein-benoxinate products worldwide?

No. US Patent 10,632,197 has territorial effect in the United States. Foreign protection depends on corresponding national applications, granted claims, maintenance, and expiration in each jurisdiction.

References

United States Patent and Trademark Office. (2020). U.S. Patent No. 10,632,197.
U.S. Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (n.d.-b). Drugs@FDA: FDA-approved drugs.
35 U.S.C. § 154. Patent term.
21 U.S.C. § 355(j). Abbreviated applications for new drugs.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bausch Lomb Ireland	FLUORESCEIN SODIUM AND BENOXINATE HYDROCHLORIDE	benoxinate hydrochloride; fluorescein sodium	SOLUTION/DROPS;OPHTHALMIC	211039-001	Mar 9, 2020		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y			OCULAR EXAMINATION, INTRAOCULAR PRESSURE MEASUREMENT, OR REMOVAL OF FOREIGN BODIES OR SUTURES, IN ADULT AND PEDIATRIC PATIENTS REQUIRING A DISCLOSING AGENT IN COMBINATION WITH A TOPICAL OPHTHALMIC ANESTHETIC	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3082603	⤷ Start Trial
China	111565761	⤷ Start Trial
European Patent Office	3710069	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2019099739	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,632,197

Which drugs does patent 10,632,197 protect, and when does it expire?

Summary for Patent: 10,632,197