US Patent 9,192,571: Ketorolac-Carboxymethylcellulose Ophthalmic Patent Scope and Landscape

US Patent No. 9,192,571 protects a narrow, commercially relevant formulation of preservative-free ketorolac ophthalmic solution. The central combination is 0.45% w/v ketorolac, approximately 0.5% w/v carboxymethylcellulose, and a near-neutral pH, with dependent claims covering excipient selection, viscosity, postoperative use, dosing, visual-acuity outcomes, and absorption.

The patent was issued to Allergan, Inc. on Nov. 24, 2015, from an application claiming priority to a 2012 provisional filing. Its nominal expiration date is Dec. 10, 2033, subject to any applicable patent-term adjustment. The patent is directed to formulation and use limitations, not to ketorolac generally. A competing product that changes the ketorolac concentration, omits carboxymethylcellulose, uses a materially different viscosity grade, or falls outside the claimed pH range may avoid literal infringement, although the full patent family and doctrine of equivalents must be assessed.

What does US Patent 9,192,571 protect?

The patent protects topical aqueous ophthalmic solutions combining ketorolac with carboxymethylcellulose, particularly a preservative-free formulation containing:

Limitation	Principal claim requirement
Active ingredient	0.45% w/v ketorolac
Salt form	Ketorolac tromethamine in dependent and formulation claims
Polymer	About 0.5% w/v carboxymethylcellulose
CMC grade	Combination of medium- and high-viscosity sodium CMC in dependent claims
pH	Approximately 6.8 to 7.4 in claim 1; about 6.8 in claims 5 and 17-26
Preservative	Absent from claim 1 formulation
Additional excipients	Sodium chloride and sodium citrate dihydrate in claims 17-26
pH adjustment	Sodium hydroxide and hydrochloric acid in claim 20
Viscosity	10-30 centipoise in claim 12
Administration	Once or twice daily, including perioperative administration
Indications	Ocular pain or inflammation, including postoperative pain after photorefractive keratectomy
Functional outcomes	Increased ocular absorption, visual-acuity improvement, and healing-related outcomes

The broadest practical formulation concept is claim 1. Claims 17 and 26 narrow the composition by specifying ketorolac tromethamine, sodium chloride, sodium citrate dihydrate, carboxymethylcellulose, water, and a pH of about 6.8.

How are the independent and dependent claims structured?

Claim 1: the principal formulation claim

Claim 1 requires all of the following:

A topical aqueous ophthalmic solution.
Use for treating pain or inflammation.
0.45% w/v ketorolac.
About 0.5% w/v carboxymethylcellulose.
No preservative.
pH of approximately 6.8-7.4.

A product lacking any one of these limitations may avoid literal infringement of claim 1. The most important commercial limitations are the ketorolac concentration, CMC concentration, preservative-free status, and pH.

The phrase “for use in treating pain or inflammation” is less restrictive than the numerical formulation limitations. A product label directed to postoperative ocular pain would create a stronger infringement case than a product labeled solely for a different ophthalmic indication.

Claims 2-16: formulation, performance, and use limitations

These claims add specific technical or clinical conditions:

Claim 2 requires ketorolac tromethamine.
Claims 3 and 25 require medium- and high-viscosity CMC.
Claim 4 requires 0.5% w/v CMC.
Claim 5 specifies pH 6.8.
Claim 6 excludes surfactants and chelators.
Claim 7 covers postoperative photorefractive keratectomy pain.
Claims 8 and 16 recite at least one-line and three-line visual-acuity improvement.
Claim 9 identifies a specific excipient system.
Claim 10 recites increased ocular absorption compared with ketorolac alone.
Claim 11 requires the racemic R-(+) and S-(-) ketorolac tromethamine mixture.
Claim 12 requires 10-30 cps viscosity.
Claim 13 covers administration before or after surgery.
Claim 14 recites increased healing time compared with preservative-containing ketorolac solutions.
Claim 15 specifies twice-daily administration.

Claims directed to clinical results can create proof issues. A generic or follow-on manufacturer may have difficulty determining infringement from composition testing alone if a claim requires a visual-acuity or absorption result. Claims 2-6, 9, 11, and 12 are more suitable for analytical comparison because they focus on measurable formulation characteristics.

Claims 17-26: specified formulation platform

Claims 17-26 identify a more detailed composition:

0.45% w/v ketorolac tromethamine;
0.5% w/v carboxymethylcellulose;
approximately 0.7% w/v sodium chloride;
approximately 0.2% sodium citrate dihydrate;
pH about 6.8;
water;
optional or required pH adjustment using sodium hydroxide and hydrochloric acid;
once-daily or twice-daily administration;
perioperative use.

Claims 17 and 26 are particularly important for product comparison because they recite a recognizable excipient profile. A product containing the same active ingredient, polymer, electrolyte system, citrate buffer, and pH would present a high literal-infringement risk.

What formulation is most exposed to US Patent 9,192,571?

The highest-risk formulation is a preservative-free ophthalmic solution with the following profile:

Parameter	High-risk profile
Ketorolac	0.45% w/v ketorolac tromethamine
CMC	Approximately 0.5% w/v sodium CMC
CMC type	Medium- and high-viscosity grades
Sodium chloride	Approximately 0.7% w/v
Sodium citrate dihydrate	Approximately 0.2% w/v
pH	Approximately 6.8
Viscosity	10-30 cps
Preservative	None
Use	Postoperative ocular pain or inflammation
Dosing	Once or twice daily

A generic that matches this profile could face substantial exposure even if it uses a different trade name, container, packaging configuration, or manufacturing process.

Which formulation changes may create a design-around?

Potential design-around positions include:

Design-around variable	Potential effect
Ketorolac concentration	Moving materially away from 0.45% may avoid claims requiring that concentration
Polymer	Replacing CMC with another viscosity-enhancing agent may avoid CMC limitations
CMC concentration	Concentrations materially different from about 0.5% may reduce literal infringement risk
pH	Moving outside approximately 6.8-7.4 may avoid claim 1, but claims with “about 6.8” require technical analysis
Preservative	Adding a preservative may avoid the “no preservative” limitation of claim 1, but could affect product tolerability and other claims
Buffer system	Omitting sodium citrate or using a different buffer may avoid claims 17-26
CMC grade	Using only low-viscosity or a different CMC grade may avoid claims requiring medium/high viscosity combinations
Viscosity	A viscosity below 10 cps or above 30 cps may avoid claim 12
Dose frequency	A dosing change may avoid some method claims but generally will not avoid composition claims
Salt form	Using a different ketorolac form may avoid claims specifically requiring ketorolac tromethamine, but not necessarily claim 1

Design-around analysis must account for the “about” language. Courts generally evaluate the term in view of the intrinsic evidence, specification, prosecution history, and technical meaning. A formulation at 0.49% CMC cannot be assumed to fall outside “about 0.5%.”

What is the Orange Book status of US Patent 9,192,571?

US Patent 9,192,571 is associated with the Acuvail ketorolac tromethamine ophthalmic solution product, NDA 022212, approved by the FDA in 2009. Acuvail contains 0.45% ketorolac tromethamine and is marketed as a preservative-free ophthalmic solution for postoperative ocular inflammation and pain. The FDA-approved labeling identifies ketorolac tromethamine as the active ingredient and describes the product’s ophthalmic administration and postoperative use.[2]

The relevant regulatory framework is:

Regulatory item	Status
Drug	Acuvail
Active ingredient	Ketorolac tromethamine
Strength	0.45% ophthalmic solution
NDA	022212
FDA approval	2009
Patent type	Formulation and method-of-use protection
Patent number	US 9,192,571
Nominal expiration	Dec. 10, 2033
Generic pathway	ANDA with Paragraph IV or other applicable certification

The Orange Book listing is important because an ANDA applicant must address listed patents. A Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed can trigger Hatch-Waxman litigation if the NDA holder files suit within the statutory period.[3]

When does US Patent 9,192,571 lose exclusivity?

The nominal patent expiration date is Dec. 10, 2033. That date derives from the 20-year term measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any terminal disclaimer.

The patent’s commercial exclusivity is not identical to FDA regulatory exclusivity. Acuvail’s original new-drug exclusivity period expired years before the patent term. The remaining barrier is therefore primarily patent-based rather than new-drug-exclusivity-based.

A generic applicant may file an ANDA before patent expiration under the Hatch-Waxman framework. Commercial launch before expiration can occur through:

successful Paragraph IV litigation;
a final judgment of invalidity or noninfringement;
a settlement permitting an agreed launch date;
a licensed launch;
an authorized generic arrangement; or
expiration of the relevant patent claims.

The patent’s expiration date does not by itself establish the earliest possible generic launch date because litigation, settlement, regulatory approval, pediatric exclusivity, and other listed patents may control market entry.

How strong is the patent estate for Acuvail?

The patent estate is strongest against products that copy the commercial formulation closely. The claims create several layers:

A broad formulation layer based on ketorolac, CMC, pH, and preservative-free status.
A narrower excipient layer based on sodium chloride and citrate.
A polymer-grade layer based on medium- and high-viscosity CMC.
A physical-property layer based on viscosity.
A clinical-use layer based on postoperative treatment and dosing.
A performance layer based on absorption, healing, and visual acuity.

The formulation claims are commercially stronger than the outcome claims because they can be tested through composition analysis. The “about” limitations provide some tolerance around the stated concentrations and pH, while also creating claim-construction uncertainty.

Principal validity considerations

Potential validity issues would likely focus on:

anticipation by earlier ketorolac ophthalmic formulations;
obviousness of combining ketorolac with CMC;
obviousness of the claimed excipient and pH ranges;
written-description support for the claimed concentration and performance results;
enablement across the full scope of “about” ranges;
indefiniteness of functional results such as increased healing time or visual-acuity improvement;
claim-construction issues created by overlapping or internally repetitive claims.

The patent’s practical value depends on whether the specification demonstrates an unexpected benefit from combining ketorolac with CMC, such as increased ocular absorption, reduced dosing frequency, improved postoperative tolerability, or visual-acuity outcomes. Evidence of unexpected results can materially strengthen the nonobviousness position.

What patent litigation and Paragraph IV risks affect generic entry?

A generic applicant seeking approval for 0.45% ketorolac tromethamine ophthalmic solution would typically compare its proposed formulation against the listed patent claims. The highest litigation risk would arise where the proposed product has:

0.45% ketorolac tromethamine;
approximately 0.5% CMC;
no preservative;
pH near 6.8;
sodium chloride and sodium citrate;
medium- and high-viscosity CMC;
postoperative ocular-pain labeling.

The applicant may pursue a Paragraph IV certification, a section viii statement carving out patented use language, or a formulation design-around. A section viii strategy is more difficult where the patent claims the composition itself rather than only the postoperative indication.

Generic strategy	Main advantage	Main risk
Paragraph IV challenge	Can seek approval before expiration if successful	Patent litigation and possible 30-month stay
Section viii carve-out	Avoids some method-of-use claims	Does not avoid formulation claims
Formulation design-around	Reduces literal infringement risk	May require new stability, tolerability, or bioequivalence work
Delayed launch	Avoids litigation cost	Defers revenue and may permit first-filer competition
Licensed entry	Provides certainty	Requires economic concessions to patent holder

What are the manufacturing and intellectual-property barriers?

The patent does not claim a complex synthesis of ketorolac. Its manufacturing relevance is formulation-centered. Key technical barriers include:

achieving uniform dispersion of CMC;
controlling viscosity within the claimed range;
maintaining pH near 6.8;
preserving ketorolac stability without preservatives;
controlling microbial risk in a preservative-free multidose or unit-dose system;
reproducing the medium/high-viscosity CMC combination;
demonstrating container-closure compatibility;
establishing ophthalmic sterility and particulate control.

A manufacturer can potentially avoid the patent through a different polymer or buffer system, but that may introduce separate regulatory and commercial risks. A technically noninfringing formulation may not match the reference product’s residence time, comfort, absorption, dosing frequency, or postoperative performance.

How does the patent compare with older ketorolac ophthalmic patents?

US 9,192,571 is narrower than foundational patents covering ketorolac ophthalmic use or ketorolac formulations generally. Earlier ketorolac patents may have expired or may protect different compositions, concentrations, delivery systems, or therapeutic uses.

Patent category	Typical scope	Relevance to US 9,192,571
Active-ingredient patents	Ketorolac compound or salt	Generally expired or unrelated to this formulation
Early ophthalmic-use patents	Treatment of ocular inflammation or pain	May overlap in indication but not the specific CMC formulation
Conventional ketorolac solutions	Ketorolac concentration, buffers, preservatives	Prior-art relevance and possible separate listings
CMC-enhanced formulations	Ketorolac plus viscosity-enhancing polymer	Direct technical overlap
Packaging patents	Unit-dose containers or dispensing systems	Separate infringement analysis
Manufacturing patents	Sterilization, mixing, filling, or stability processes	May create additional barriers independent of US 9,192,571

The key commercial question is not whether ketorolac is patent-protected generally. It is whether a competing product reproduces the claimed ketorolac-CMC formulation and whether other patents remain listed for the reference product.

What is the competitive landscape for ketorolac ophthalmic products?

The market includes several ketorolac products differentiated by strength, preservative status, dosing regimen, and indication. Products based on conventional ketorolac solutions may avoid the specific CMC combination in US 9,192,571. Acuvail’s commercial differentiation is its 0.45% preservative-free formulation and postoperative dosing profile.

Relevant competitive categories include:

0.5% ketorolac tromethamine ophthalmic solutions;
0.45% preservative-free ketorolac solutions;
other topical ophthalmic NSAIDs, including nepafenac, bromfenac, and diclofenac;
products using alternative viscosity enhancers;
unit-dose versus multidose delivery systems.

The patent is most relevant to a competitor seeking to duplicate Acuvail’s formulation rather than to all topical ophthalmic NSAID products.

What revenue exposure does the patent create?

Revenue exposure is concentrated in the 0.45% preservative-free ketorolac segment. A successful generic that matches the claimed formulation could compete directly with Acuvail and potentially obtain approval through an ANDA. The commercial impact depends on:

the number of approved generic applicants;
the earliest non-infringing launch date;
reimbursement and formulary substitution;
ophthalmic surgeon prescribing patterns;
unit-dose manufacturing capacity;
price erosion after generic entry;
the presence of alternative ketorolac strengths and NSAIDs.

The patent does not block the entire ophthalmic NSAID market. Its exposure is product-specific and formulation-specific.

Key Takeaways

US 9,192,571 is a formulation patent centered on 0.45% ketorolac and approximately 0.5% carboxymethylcellulose.
The highest-risk formulation includes ketorolac tromethamine, medium/high-viscosity sodium CMC, sodium chloride, sodium citrate, pH about 6.8, and no preservative.
Claims 1 and 17-26 provide the principal commercial protection.
Claims covering measurable composition characteristics are stronger for enforcement than claims based solely on visual acuity, healing, or absorption outcomes.
The nominal patent expiration date is Dec. 10, 2033, subject to patent-term adjustment and related patent rights.
A generic applicant could pursue Paragraph IV, a section viii carve-out, a design-around, or a negotiated launch.
Changing the polymer, CMC concentration, pH, preservative status, buffer system, or ketorolac strength may reduce literal infringement risk.
Formulation design-around work must be balanced against ophthalmic stability, sterility, tolerability, and bioequivalence requirements.
The patent does not cover ketorolac ophthalmic products generally or the entire topical ophthalmic NSAID market.

FAQs About US Patent 9,192,571

Does US Patent 9,192,571 cover all ketorolac eye drops?

No. It focuses on specific aqueous formulations containing ketorolac and carboxymethylcellulose, with additional concentration, pH, excipient, and preservative limitations.

Can a generic use 0.45% ketorolac without infringing?

Potentially, but concentration alone is not determinative. A product containing 0.45% ketorolac may still infringe if it also includes the claimed CMC, pH, preservative, viscosity, or excipient combination.

Does adding a preservative avoid the patent?

It may avoid the “no preservative” limitation in claim 1, but claims must be reviewed individually. Adding a preservative may not avoid every claim if another claim lacks that limitation or if separate patent rights apply.

Is carboxymethylcellulose required in every claim?

CMC is central to the claims supplied. Claims 1, 4, 17, and 26 expressly require it, while other claims depend on formulations containing CMC. A product using a different viscosity-enhancing polymer may have a stronger design-around position.

Does FDA approval end the patent?

No. FDA approval and patent expiration are separate events. An ANDA may be approved before patent expiration depending on the certification, litigation outcome, settlement terms, and other listed patents, but commercial launch may remain restricted.

References

United States Patent and Trademark Office. (2015). US Patent No. 9,192,571, Ophthalmic compositions comprising ketorolac and carboxymethylcellulose.
U.S. Food and Drug Administration. (2009). Acuvail prescribing information: Ketorolac tromethamine ophthalmic solution, 0.45%.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
U.S. Code, 35 U.S.C. §§ 154, 156, and 271.
U.S. Code, 21 U.S.C. § 355(j).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Abbvie	ACUVAIL	ketorolac tromethamine	SOLUTION/DROPS;OPHTHALMIC	022427-001	Jul 22, 2009		RX	Yes	Yes	9,192,571	⤷ 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

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	2009202969	Jul 23, 2009

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	E538775	⤷ Start Trial
Australia	2009202969	⤷ Start Trial
Australia	2009222016	⤷ Start Trial
Australia	2010289618	⤷ Start Trial
Australia	2011237646	⤷ Start Trial
Brazil	PI0909100	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,192,571

Which drugs does patent 9,192,571 protect, and when does it expire?

Summary for Patent: 9,192,571