United States Patent 9,993,471: Cetirizine Ophthalmic Formulation Patent Scope, Expiration, and Generic Risk

US Patent No. 9,993,471 protects methods of treating allergic conjunctivitis with a topical ophthalmic cetirizine formulation. Its commercial significance is tied to Zerviate, a cetirizine hydrochloride ophthalmic solution approved by the FDA for ocular itching associated with allergic conjunctivitis.

The patent is primarily a method-of-use and formulation-specific patent. It does not broadly cover all cetirizine products, all antihistamine eye drops, or all ophthalmic cetirizine formulations. Infringement requires practice of the claimed treatment method with a formulation meeting the specified concentration, excipient, pH, and solubilizer limitations.

What does US Patent 9,993,471 cover?

US 9,993,471 covers topical administration to the eye of cetirizine in a defined ophthalmic vehicle for treating the signs and symptoms of allergic conjunctivitis.

The independent claims are claims 1 and 3:

Claim	Claim type	Cetirizine concentration	Formulation limitation	Therapeutic limitation
1	Method of treatment	0.1% to 0.25% w/v	Specified excipients, pH 7, no cyclodextrin or other solubilizing compound	Allergic conjunctivitis
3	Method of treatment	0.1% w/v	Substantially specified composition, pH 7, no cyclodextrin or other solubilizing compound	Allergic conjunctivitis

Dependent claims 2, 5, and 6 identify ocular itching, ocular redness, lid swelling, and associated nasal symptoms. Claims 4 and 6 specify cetirizine hydrochloride or cetirizine dihydrochloride.

The patent therefore has two principal protection layers:

A concentration range claim covering 0.1% through 0.25% cetirizine.
A narrower composition claim directed to a 0.1% cetirizine formulation with a defined excipient system.

How broad is claim 1 of US 9,993,471?

Claim 1 is relatively narrow because it requires every material limitation in the formulation.

The claim requires:

Cetirizine hydrochloride or cetirizine dihydrochloride.
A concentration from 0.1% to 0.25% w/v.
Cetirizine as the only active agent.
Topical ophthalmic administration to an eye.
Treatment of allergic conjunctivitis.
A vehicle containing:
- 1% polyethylene glycol 400;
- 0.2% anhydrous dibasic sodium phosphate;
- 0.25% hypromellose;
- 0.1% polysorbate 80;
- 1.2% to 1.8% glycerin;
- 0.025% edetate disodium;
- 0.01% benzalkonium chloride; and
- purified water.
A pH of 7.
No cyclodextrin or other solubilizing compound.

A product outside any one of these limitations may avoid literal infringement of claim 1. Examples include a formulation with:

0.3% cetirizine;
a concentration below 0.1%;
a different buffer;
no benzalkonium chloride;
a different viscosity agent;
glycerin outside the claimed range;
a different pH;
a cyclodextrin;
another active pharmaceutical ingredient; or
a different route of administration.

The claim still may present infringement issues under the doctrine of equivalents, but the multiple excipient limitations create substantial design-around opportunities.

What formulation is protected by US 9,993,471?

The claimed formulation closely tracks the formulation used in Zerviate, which contains cetirizine hydrochloride ophthalmic solution at 0.24% w/v. The FDA-approved product contains cetirizine hydrochloride equivalent to 0.24% cetirizine hydrochloride concentration and uses a vehicle containing glycerin, polyethylene glycol 400, hypromellose, polysorbate 80, phosphate buffer, edetate disodium, benzalkonium chloride, and water.[2]

The commercial product is administered as one drop in each affected eye twice daily, approximately eight hours apart. The FDA indication is treatment of ocular itching associated with allergic conjunctivitis.[2]

Formulation comparison

Feature	Patent claim 1	Zerviate labeling	Infringement relevance
Active ingredient	Cetirizine HCl or dihydrochloride	Cetirizine hydrochloride	Direct alignment
Concentration	0.1% to 0.25% w/v	0.24%	Within claimed range
Active agents	Cetirizine only	Cetirizine only	Direct alignment
PEG 400	1%	1%	Direct alignment
Hypromellose	0.25%	0.25%	Direct alignment
Polysorbate 80	0.1%	0.1%	Direct alignment
Glycerin	1.2% to 1.8%	1.8%	At upper claim boundary
Edetate disodium	0.025%	0.025%	Direct alignment
Benzalkonium chloride	0.01%	0.01%	Direct alignment
pH	7	Approximately 7	Direct or near-direct alignment
Cyclodextrin	Excluded	Not used	Direct alignment

The commercial product appears to practice the core formulation limitations of claim 1. The patent is therefore commercially relevant to Zerviate despite its method-of-treatment claim format.

What is the scope of claim 3?

Claim 3 is narrower than claim 1 because it requires a formulation “consisting of” the listed components and specifies 0.1% cetirizine rather than a range up to 0.25%.

A claim using “consisting of” generally limits the composition to the named components, although minor impurities, manufacturing residues, and components that do not materially affect the claimed characteristics may raise separate claim-construction questions.

Claim 3 has two apparent drafting issues:

Edetate disodium appears twice in the supplied text, once at 0.025%.
The claim states 0.1% cetirizine but does not initially identify the salt form. Claim 4 supplies the hydrochloride or dihydrochloride limitation.

These issues do not eliminate the independent claim. A court would normally interpret the claim in light of the specification, prosecution history, and the claim set as a whole. Claim 3 is materially narrower than claim 1 and is less likely to cover a formulation that departs from the listed excipient system.

When does US Patent 9,993,471 expire?

The patent issued on June 12, 2018. The public patent record identifies a nominal expiration date in November 2033, subject to any applicable patent-term adjustment.[1]

Milestone	Date or status
US patent application family	Priority claims reflected in the patent record
Patent issued	June 12, 2018
Patent number	US 9,993,471 B2
Nominal expiration	November 2033
Patent-term adjustment	Must be accounted for in the USPTO patent record
FDA product association	Zerviate, cetirizine ophthalmic solution

The patent term is separate from FDA regulatory exclusivity. FDA approval does not itself determine patent expiration, and an Orange Book listing does not extend the statutory patent term.

What is the Orange Book status of Zerviate?

Zerviate is an FDA-approved small-molecule ophthalmic drug, not a biologic. The relevant abbreviated approval pathway for a competing product would generally be an ANDA, not a biosimilar application.

The Orange Book may list patents submitted by the NDA holder for the approved drug. A listed patent can require an ANDA applicant to make one of the statutory certifications under section 505(j)(2)(A)(vii) of the Federal Food, Drug, and Cosmetic Act.[3]

The main certification categories are:

Paragraph I: no patent information has been submitted.
Paragraph II: the patent has expired.
Paragraph III: the applicant will wait until patent expiration.
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV certification can trigger patent litigation if the NDA holder files suit within 45 days of receiving notice. The filing of litigation can impose a statutory 30-month stay on final ANDA approval, subject to the statutory rules governing the stay.[3]

The patent’s practical Orange Book importance depends on whether it is currently listed against the relevant Zerviate NDA and whether the listing has been removed, expired, or superseded by a later patent.

Which companies could challenge US 9,993,471?

Potential challengers would be generic ophthalmic manufacturers seeking an ANDA for cetirizine ophthalmic solution. A Paragraph IV strategy could target the patent through:

Noninfringement based on a different excipient system.
Noninfringement based on a different concentration.
Noninfringement based on a different pH.
Invalidity for lack of written description or enablement.
Obviousness based on prior cetirizine formulations, ophthalmic antihistamines, and known excipient systems.
Indefiniteness or claim-construction arguments involving “other solubilizing compound.”
Treatment-method arguments based on the approved labeling and the scope of induced infringement.

A generic applicant could also pursue a formulation that does not practice the patented method. For example, a formulation using a different buffer or omitting benzalkonium chloride may reduce literal infringement risk. A product with a different indication or labeling strategy could create further distinctions, although labeling does not automatically eliminate induced-infringement exposure.

No biosimilar challenge is relevant because cetirizine is a chemically synthesized small molecule and Zerviate is not regulated as a biologic.

How strong is the patent estate for cetirizine ophthalmic products?

US 9,993,471 has meaningful commercial strength against a copycat of the approved Zerviate formulation. Its strength is lower against technically differentiated products.

Strengths

The claim covers the marketed 0.24% cetirizine ophthalmic formulation.
The excipient list is detailed and directly maps to the commercial product.
The method is tied to a recognized indication, allergic conjunctivitis.
The concentration range captures both the marketed 0.24% product and lower-strength products down to 0.1%.
Claims 2, 5, and 6 provide narrower symptom-specific fallbacks.

Weaknesses

The claims are not composition claims directed to cetirizine eye drops in the abstract.
A competitor may design around the excipient system.
The absence of cyclodextrin and other solubilizing compounds is a limiting negative element.
The exact pH requirement may create a noninfringement path if the competing product is materially outside pH 7.
The method claims require administration to treat allergic conjunctivitis, creating potential disputes over the generic label and induced infringement.
Claim 3 is unusually narrow and contains an apparent duplicated excipient limitation in the supplied text.

The patent is strongest against a product that copies Zerviate’s formulation and labeling. It is weaker against a formulation using a different solubilization strategy, preservative system, buffer, viscosity modifier, or dose concentration.

What generic launch scenarios exist?

Scenario	Patent impact	Commercial timing
Generic copies 0.24% formulation	High Paragraph IV and litigation risk	Launch depends on patent outcome, settlement, or expiration
Generic uses different excipients but 0.24% cetirizine	Moderate risk	Requires detailed claim chart and inducement analysis
Generic uses 0.1% cetirizine with the same vehicle	Potentially high risk	Claim 1 may apply; claim 3 may also be implicated
Generic uses concentration below 0.1%	Lower literal risk under claims supplied	Clinical and regulatory viability must be established
Generic uses a cyclodextrin	Potential design-around	Must assess other patents and regulatory equivalence
Generic uses a different active antihistamine	Outside this patent	Competes with cetirizine without practicing the claims
Generic launches after patent expiration	Patent risk substantially reduced	FDA approval still depends on ANDA requirements

A generic applicant seeking an early launch would likely evaluate a Paragraph IV certification against the patent, a formulation design-around, or both. The commercial choice depends on whether the product can remain therapeutically equivalent while avoiding the claimed vehicle.

What litigation and settlement issues affect the patent?

The supplied record does not establish a specific final judgment, settlement, or ANDA litigation outcome concerning US 9,993,471. The principal legal exposure would arise if an ANDA applicant files a Paragraph IV certification and the NDA holder brings an infringement action within the statutory notice period.

A settlement could provide:

A fixed generic entry date;
A license before patent expiration;
A formulation-specific carve-out;
Restrictions on the generic label;
A supply or commercial agreement; or
A covenant not to sue for a defined product.

Any settlement involving an FDA-listed patent may be subject to FTC and FDA review under applicable reporting requirements. A settlement date alone would not establish the patent’s expiration date or the generic’s actual launch date.

How does US 9,993,471 compare with generic and competing antihistamine products?

US 9,993,471 is specific to cetirizine ophthalmic treatment. It does not block competing products based on olopatadine, ketotifen, alcaftadine, bepotastine, or other antihistamine or mast-cell stabilizing agents.

Product class	Active ingredient	Relationship to US 9,993,471
Zerviate	Cetirizine hydrochloride	Directly relevant
Patanol, Pataday	Olopatadine	Outside the claimed active ingredient
Alaway and similar products	Ketotifen	Outside the claimed active ingredient
Lastacaft	Alcaftadine	Outside the claimed active ingredient
Bepreve	Bepotastine	Outside the claimed active ingredient
Generic cetirizine ophthalmic solution	Cetirizine	Potentially relevant, depending on formulation and labeling

The patent does not create exclusivity over the allergic-conjunctivitis market. It creates a targeted barrier around one active ingredient and one formulation architecture.

Key Takeaways

US 9,993,471 is a method-of-treatment patent covering topical cetirizine ophthalmic formulations for allergic conjunctivitis.
Claim 1 covers 0.1% to 0.25% cetirizine with a specified excipient vehicle, pH 7, and no cyclodextrin or other solubilizer.
Claim 3 is narrower and focuses on a 0.1% formulation with a substantially closed composition.
The claims closely correspond to Zerviate’s 0.24% cetirizine ophthalmic solution.
The patent’s nominal expiration is in November 2033, subject to patent-term adjustment.
A generic copy of Zerviate would face substantial Paragraph IV and induced-infringement risk.
Formulation design-arounds using different excipients, pH, preservatives, solubilizers, or concentrations may reduce literal infringement risk.
Biosimilar litigation is irrelevant because cetirizine is a small-molecule drug.
The patent does not block competing antihistamine products containing olopatadine, ketotifen, alcaftadine, or bepotastine.
The commercial value of the patent depends on the continuing Orange Book listing, the existence of continuation patents, and any ANDA settlement or litigation outcome.

FAQs

Does US 9,993,471 cover all cetirizine eye drops?

No. It covers methods using a defined concentration and excipient system. A cetirizine eye drop with materially different formulation characteristics may fall outside the asserted claims.

Can a generic use 0.24% cetirizine and avoid the patent?

Possibly, but changing only one excipient may not be sufficient if the product still satisfies the remaining limitations or is equivalent under the doctrine of equivalents. A complete formulation and labeling analysis is required.

Is Zerviate protected by a composition-of-matter patent?

US 9,993,471, based on the claims supplied, is not a broad composition-of-matter claim. It is a formulation-specific method patent. Other patents may provide separate protection.

Does the patent cover nasal symptoms?

Dependent claims identify associated nasal symptoms, but the independent claims require topical administration to an eye and treatment of allergic conjunctivitis. The nasal-symptom language does not convert the patent into a general nasal cetirizine patent.

Can a company launch an alternative antihistamine during the patent term?

Yes. A product using a different active ingredient, such as olopatadine, ketotifen, alcaftadine, or bepotastine, is outside the cetirizine limitations of the claims supplied, although other patents may apply.

References

United States Patent and Trademark Office. (2018). United States Patent No. 9,993,471 B2.
U.S. Food and Drug Administration. (2024). Zerviate (cetirizine hydrochloride ophthalmic solution) prescribing information.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
United States Code, 35 U.S.C. §§ 154, 271, and 282.

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	ZERVIATE	cetirizine hydrochloride	SOLUTION/DROPS;OPHTHALMIC	208694-001	May 30, 2017		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF OCULAR ITCHING ASSOCIATED WITH ALLERGIC CONJUNCTIVITIS	⤷ 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	2755679	⤷ Start Trial
European Patent Office	2408453	⤷ Start Trial
European Patent Office	2547340	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,993,471

Which drugs does patent 9,993,471 protect, and when does it expire?

Summary for Patent: 9,993,471