US Patent 9,662,398: Nepafenac Ophthalmic Suspension Claims, Expiration, Litigation and Patent Landscape

US Patent 9,662,398 protects a specific ophthalmic suspension architecture built around nepafenac, carbomer, guar-derived galactomannan and borate. The broadest independent claim requires all four components within defined concentration ranges. Claim 32 narrows protection to an Ilevro-type formulation containing 0.3% nepafenac, 0.4% carbomer, 0.2% native guar, 0.5% boric acid, sodium carboxymethylcellulose, sodium chloride, propylene glycol, benzalkonium chloride and edetate disodium.

The patent is assigned to Alcon Research, Ltd. and is directed to formulation technology rather than nepafenac’s ophthalmic use generally. Its principal commercial relevance is the 0.3% nepafenac product Ilevro. The nominal patent term extends to December 17, 2030, subject to any patent-term adjustment, terminal disclaimer or later USPTO correction.[1]

What patent is US 9,662,398 and who owns it?

US Patent 9,662,398 is a formulation patent covering topically administrable aqueous ophthalmic suspensions containing nepafenac and a defined viscosity, suspension-stability and particle-dispersion system.

Item	Data
Patent	US 9,662,398 B2
Title	Ophthalmic pharmaceutical compositions containing nepafenac
Patent type	Utility patent
Technology	Aqueous ophthalmic suspension
Active ingredient	Nepafenac
Patent holder	Alcon Research, Ltd.
Grant date	May 30, 2017
Earliest priority date	December 17, 2010
Nominal expiration	December 17, 2030
Commercial product most closely associated	Ilevro, nepafenac ophthalmic suspension 0.3%
FDA product type	Small-molecule ophthalmic drug
Biosimilar pathway	Not applicable

The patent does not claim every nepafenac eye drop. It requires a combination of excipient classes and concentration limitations. A formulation using nepafenac without the claimed carbomer-galactomannan-borate system would generally fall outside the literal scope of claim 1.

What does claim 1 of US 9,662,398 cover?

Claim 1 is the broadest composition claim. It requires each of the following elements:

Required element	Claimed limitation
Dosage form	Topically administrable aqueous ophthalmic suspension
Carboxyvinyl polymer	0.1% to 0.5% w/v
Polymer identity	Carbomer
Galactomannan	0.1% to 0.4% w/v
Galactomannan identity	Guar, native guar or hydroxypropyl guar
Borate	0.4% to 2.0% w/v
Active compound	Sparingly soluble particulate compound
Active identity	Nepafenac
Nepafenac concentration	0.1% to 1.0% w/v
Solubility definition	0.001% to 0.1% w/v in water at 25°C

The claim is structurally cumulative. A competing product must contain the claimed aqueous suspension, carbomer, qualifying galactomannan, borate and nepafenac concentration to satisfy all claim 1 limitations literally.

The claim also incorporates a functional solubility characterization for the particulate compound. Because nepafenac is expressly identified in the claim, the principal dispute would likely concern formulation composition, concentration, particle characteristics and claim interpretation rather than whether nepafenac qualifies as the claimed compound.

How do claims 2 through 31 narrow the patent scope?

Claims 2 through 31 create dependent fallback positions. They are commercially important because they track common ophthalmic formulation components and the concentrations associated with the marketed product.

Claims	Limitation	Legal and commercial significance
2, 16	pH of 5.0 to 7.2; claim 16 specifies pH 7.0	Captures neutral-to-mildly acidic ophthalmic formulations
3	Osmolality of 250 to 350 mOsm/kg	Targets physiologically tolerable ophthalmic products
4, 19, 20	Carbomer, including Carbopol 974P, at 0.4%	Narrows the polymer identity and concentration
5-7, 17	Milling agent, including sodium carboxymethylcellulose at 0.06%	Protects particle-size reduction and suspension processing
8, 9	Metal chloride salt, including sodium chloride at 0.4%	Covers tonicity adjustment
10, 18	Non-ionic hydroxyl compound, including propylene glycol at 0.5%	Adds a specific tonicity or formulation aid
11, 12	Preservative and chelating agent	Covers benzalkonium chloride and edetate disodium combinations
13-15	Carbomer, native guar, boric acid and nepafenac; claim 14 specifies concentrations; claim 15 specifies 400 nm particles	Provides a concentrated commercial-formulation claim set
21, 22	Guar or native guar at 0.2%	Narrows galactomannan selection
23-25	Boric acid at 0.4% to 0.6%, including 0.5%	Targets the borate species used in the commercial formulation
26, 27	Nepafenac at 0.25% to 0.35%, including 0.3%	Directly captures Ilevro’s active concentration
28-31	Chelating agent, including edetate disodium at 0.01%	Adds a formulation-stability limitation

Claims 4, 13, 14, 19, 20, 22, 25 and 27 are especially significant because they converge on the commercial 0.3% nepafenac formulation. Claims 5 through 7 and 17 add a particle-processing limitation that may be relevant to manufacturing records, not only finished-product testing.

What formulation is protected by claim 32?

Claim 32 is an independent “consisting essentially of” claim. It protects a defined formulation containing:

Component	Concentration
Nepafenac	0.3% w/v
Carbomer	0.4% w/v
Native guar	0.2% w/v
Boric acid	0.5% w/v
Sodium carboxymethylcellulose	0.06% w/v
Sodium chloride	0.4% w/v
Propylene glycol	0.5% w/v
Benzalkonium chloride	0.005% w/v
Edetate disodium	0.01% w/v
Purified water	Balance

“Consisting essentially of” generally permits unlisted ingredients that do not materially change the basic and novel characteristics of the composition. The claim therefore differs from an absolute closed-composition claim. A generic manufacturer could face infringement risk even if it adds an excipient, depending on whether that excipient materially changes the claimed suspension system.

Claim 32 is narrower than claim 1 but commercially stronger against an accused product that reproduces the Ilevro formulation. The claim also creates a potential ingredient-by-ingredient comparison framework for ANDA litigation.

When does US Patent 9,662,398 lose exclusivity?

The nominal expiration date is December 17, 2030, based on the earliest claimed priority date and the 20-year patent-term rule under 35 U.S.C. § 154.[1][4]

The effective date can differ if the USPTO granted patent-term adjustment. Regulatory patent listings may also show a different date from the unadjusted term. Patent expiration does not automatically establish the date on which a generic can launch because:

A separate patent may remain in force.
An ANDA applicant may obtain an earlier launch through litigation or settlement.
An authorized generic or licensed product may enter under contractual terms.
A patent may be invalidated or held unenforceable before expiration.
Regulatory exclusivity and patent protection operate under separate legal mechanisms.

For commercial diligence, December 2030 is the principal unadjusted term date associated with this patent, but the complete Ilevro entry must be evaluated with the other Orange Book-listed patents.

What is the Orange Book status of US 9,662,398?

Ilevro is FDA-approved under NDA 203793 as nepafenac ophthalmic suspension 0.3% for topical ophthalmic use in patients undergoing cataract surgery.[2][3] US 9,662,398 has been associated with the Ilevro formulation patent estate and should be evaluated with the FDA Orange Book patent listing for NDA 203793.

The Orange Book analysis has four separate components:

Issue	Assessment
Listed drug	Ilevro, nepafenac ophthalmic suspension 0.3%
NDA holder	Novartis/Alcon commercial organization
Patent category	Drug product and formulation protection
Use-code protection	Not the central feature of US 9,662,398
Small-molecule exclusivity	Applicable
Biosimilar exclusivity	Not applicable

The patent is primarily a drug-product formulation patent. It is not a biologic patent and does not create a Purple Book biosimilar barrier.

What Paragraph IV challenges affect nepafenac ophthalmic suspension?

An ANDA applicant seeking approval before the listed patents expire may file a Paragraph IV certification asserting that a listed patent is invalid, unenforceable or not infringed.[4] For US 9,662,398, the most likely technical disputes would involve:

Whether the proposed product contains a carbomer within the claimed range.
Whether its guar derivative qualifies as native guar, guar or hydroxypropyl guar.
Whether the formulation contains borate in the claimed concentration.
Whether nepafenac is present at 0.1% to 1.0% w/v.
Whether the product is an aqueous suspension rather than a solution or another dosage form.
Whether particle-size and milling-agent limitations are met.
Whether added excipients materially alter the basic and novel characteristics of claim 32.
Whether the asserted claims are anticipated or obvious over prior ophthalmic suspensions.

A Paragraph IV notice would normally trigger a patent-infringement action within 45 days and could impose a 30-month FDA approval stay under the Hatch-Waxman framework, subject to statutory exceptions.[4] The existence of a Paragraph IV certification does not itself establish that the patent is invalid or that an early generic launch is legally available.

What patent litigation affects Ilevro and nepafenac suspension products?

Alcon’s Ilevro patent estate has been relevant to ANDA activity directed at 0.3% nepafenac ophthalmic suspension. Publicly available FDA and patent records identify US 9,662,398 as a key formulation patent associated with the product.

The litigation risk is concentrated in the formulation claims rather than the active ingredient alone. Nepafenac itself is an established NSAID, and a generic manufacturer may avoid some claims by using a materially different suspension system. That strategy becomes harder if the proposed formulation uses the same combination of carbomer, guar, boric acid, particle-processing aid and 0.3% nepafenac.

A complete litigation assessment must distinguish:

Litigation issue	Relevance to US 9,662,398
Infringement	Whether every limitation of an asserted claim is present
Validity	Prior-art disclosure and obviousness of the excipient combination
Enablement	Whether the full claimed ranges are enabled
Written description	Whether the specification supports the genus and species
Prosecution history	Whether claim amendments limit construction
Settlement	Whether a generic receives a licensed or contingent entry date
Launch risk	Whether the applicant launches at risk before final resolution

No biosimilar litigation is relevant because nepafenac is a chemically synthesized small molecule.

How strong is the patent estate for Ilevro?

US 9,662,398 has meaningful formulation strength because the claims combine multiple excipient classes, concentrations and processing features. The patent is stronger against a close copy than against a deliberately redesigned product.

Strengths

Claim 1 covers a broad combination of carbomer, guar-family galactomannan, borate and nepafenac.
The nepafenac range of 0.1% to 1.0% includes both 0.1% and 0.3% products.
Dependent claims capture Carbopol 974P, native guar, boric acid and 0.3% nepafenac.
Claim 32 tracks a complete commercial formulation.
Claims 15 and 17 provide narrower positions around particle size and milling-agent concentration.

Potential vulnerabilities

Multi-excipient suspension systems may face obviousness attacks based on known ophthalmic viscosity, tonicity and suspension agents.
Broad concentration ranges can be vulnerable if prior art discloses overlapping ranges or routine optimization.
“Consisting essentially of” language may generate disputes over added excipients and materiality.
The claim’s solubility limitation may invite factual disputes concerning testing conditions and measurement methodology.
The commercial product may be easier to design around than to copy because the claim requires a particular excipient architecture.

The estate is best characterized as moderate-to-strong against literal copies and less certain against non-infringing formulation alternatives.

What generic launch scenarios exist for Ilevro?

Scenario	Commercial outcome
No successful Paragraph IV challenge	Generic entry generally deferred until patent barriers expire or are licensed
Invalidity ruling	Early entry becomes possible, subject to appeal and other patents
Non-infringement ruling	Entry may proceed if no other listed patent blocks approval
Settlement with Alcon	Entry date depends on the agreement
Formulation design-around	Generic may enter after FDA approval if it avoids all enforceable claims
Authorized generic	Earlier competition may occur through a license or Alcon-controlled supply arrangement
Patent expiration	Full open generic competition becomes more likely, although manufacturing and market access remain barriers

A 0.1% nepafenac product does not automatically avoid US 9,662,398 because claim 1 expressly covers 0.1% to 1.0% nepafenac. The excipient system remains decisive.

How does US 9,662,398 compare with other ophthalmic NSAID patents?

Product	Active ingredient	Typical dosage	Formulation profile	Biosimilar risk
Ilevro	Nepafenac	0.3%	Suspension with carbomer, guar, borate and related excipients	None
Nevanac	Nepafenac	0.1%	Earlier nepafenac ophthalmic suspension	None
Prolensa	Bromfenac	0.07%	Bromfenac ophthalmic solution/suspension technology	None
Acular/Acuvail	Ketorolac	Varies	Ketorolac ophthalmic solution technology	None
Generic nepafenac	Nepafenac	Usually 0.1% or 0.3%	Product-specific ANDA formulation	None

US 9,662,398 is distinguished from use patents because it protects the physical composition. It is also distinct from manufacturing-process patents that focus on milling, particle-size control or suspension preparation without claiming the finished combination.

What manufacturing and intellectual-property barriers exist?

The formulation requires control of several interdependent parameters:

Nepafenac particle size and distribution.
Carbomer hydration and neutralization.
Guar dispersion and viscosity.
Borate interaction with polymeric excipients.
Milling-agent concentration.
Sterility and preservative performance.
Uniform dose delivery from a multidose container.
Physical stability during storage.
Ophthalmic pH and osmolality.

A design-around may replace carbomer, substitute a non-claimed galactomannan or use a different suspension mechanism. That approach creates development risk because changes in polymer chemistry can affect viscosity, redispersibility, ocular comfort, particle settling, preservative efficacy and bioavailability.

What is the revenue exposure from US 9,662,398?

The patent’s commercial exposure is concentrated in Ilevro and potentially in 0.3% nepafenac ophthalmic suspension products using the claimed excipient system. It does not protect all ophthalmic NSAID sales or all nepafenac products.

Brand-value exposure depends on:

Ilevro sales by jurisdiction.
The number and timing of approved ANDAs.
Any settlement or license terms.
The presence of other Ilevro patents.
Generic substitution rates.
Pricing erosion after entry.
Alcon’s ability to shift demand to other postoperative ophthalmic products.

Public company reporting generally aggregates ophthalmic pharmaceutical revenue, limiting a precise product-level valuation from this patent alone.[5]

Key Takeaways

US 9,662,398 is a formulation patent, not a broad nepafenac-use patent.
Claim 1 requires carbomer, guar-family galactomannan, borate and nepafenac in specified ranges.
Claim 32 closely tracks the Ilevro 0.3% formulation.
The nominal unadjusted expiration date is December 17, 2030.
A 0.1% nepafenac product can still fall within claim 1 because the claim begins at 0.1%.
Biosimilar risk is irrelevant; any challenge proceeds through the small-molecule ANDA pathway.
The strongest infringement case concerns a product reproducing the carbomer-native-guar-boric-acid system.
The principal generic strategy is formulation design-around, Paragraph IV litigation or settlement-based entry.
Other Orange Book-listed Ilevro patents must be reviewed before calculating a definitive launch date.

FAQs

Does US 9,662,398 cover nepafenac solution products?

No. The claims require an aqueous ophthalmic suspension containing particulate nepafenac. A true solution would generally lack the required suspension and particulate features, although the formulation and claim construction would control the final infringement analysis.

Can a generic use Carbopol 974P without infringing the patent?

Potentially, but not automatically. Carbopol 974P is expressly identified in dependent claims 19 and 20. A product using that polymer together with the other claim 1 elements would face substantial infringement risk.

Does changing native guar to hydroxypropyl guar avoid infringement?

Not necessarily. Claim 1 expressly includes hydroxypropyl guar. A different galactomannan may avoid literal infringement, but the substitute must also be evaluated under the doctrine of equivalents.

Does US 9,662,398 cover the Ilevro indication?

The patent’s claims are directed primarily to the composition. The Ilevro indication is protected, if at all, by separate method-of-use or regulatory listings rather than by the composition language of this patent.

Can a manufacturer launch a generic before December 2030?

Yes, potentially through a successful Paragraph IV challenge, a non-infringement position, a settlement or license, or a formulation that avoids all enforceable listed patents. The patent expiration date alone does not determine the earliest lawful launch.

References

United States Patent and Trademark Office. (2017). U.S. Patent No. 9,662,398, Ophthalmic pharmaceutical compositions containing nepafenac.
U.S. Food and Drug Administration. (2013). Ilevro prescribing information. Alcon Laboratories, Inc.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: Ilevro, NDA 203793.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, 45th ed.
Alcon Inc. (2023). Annual report.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Harrow Eye	ILEVRO	nepafenac	SUSPENSION/DROPS;OPHTHALMIC	203491-001	Oct 16, 2012		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ 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
Argentina	080572	⤷ Start Trial
Argentina	122463	⤷ Start Trial
Australia	2010326099	⤷ Start Trial
Brazil	112012013503	⤷ Start Trial
Canada	2781254	⤷ Start Trial
Chile	2012001402	⤷ Start Trial
China	102724965	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,662,398

Which drugs does patent 9,662,398 protect, and when does it expire?

Summary for Patent: 9,662,398