Details for Patent: 9,956,289

Which drugs does patent 9,956,289 protect, and when does it expire?

Patent 9,956,289 protects VERKAZIA and is included in one NDA.

This patent has forty-three patent family members in eighteen countries.

Summary for Patent: 9,956,289

Title:	Emulsion compositions containing quaternary ammonium compounds
Abstract:	Compositions containing quaternary compounds in which the nitrogen atom is substituted by at least one alkyl group having at least 12 carbon atoms, and the composition includes at least 20% in weight by weight of the total composition, of ammonium halides in which the nitrogen atom is substituted by at least one alkyl group having at least 14 carbon atoms and more than 5%, preferably more than 7% in weight by weight of the total composition, of ammonium halides in which the nitrogen atom is substituted by at least one alkyl group having at least 16 carbon atoms. Also, ophthalmic oil-in-water emulsions containing such compositions, the ophthalmic emulsions being useful for eye care or for the treatment of eye conditions.
Inventor(s):	Laura Rabinovich-Guilatt, Gregory Lambert, Frederic LALLEMAND, Betty Philips
Assignee:	Novagali SA , Santen SAS
Application Number:	US14/943,649
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Process; Device;

United States Patent 9,956,289: Claim Scope, Patent Strength, and Competitive Landscape for Cetalkonium Chloride Emulsions

U.S. Patent No. 9,956,289 protects specific oil-in-water emulsions containing cetalkonium chloride, selected oils, and defined surfactants. The broadest claim is formulation-based and does not require cyclosporine, an active pharmaceutical ingredient, ophthalmic use, or dry-eye treatment. The patent therefore operates as a platform-emulsion patent, with narrower claims directed to ophthalmic formulations, droplet size, zeta potential, tonicity agents, cyclosporine combinations, and dry-eye kits.

The principal commercial relevance is to cationic ophthalmic emulsions associated with Novagali Pharma and Santen, including Cationorm-type formulations. The patent is materially narrower than a general patent covering any cetalkonium chloride ophthalmic emulsion because it requires a specified oil phase and one of three defined surfactants within a concentration range.

What does U.S. Patent 9,956,289 protect?

The patent’s independent composition claim requires all of the following:

Required element	Claim 1 requirement
Dosage form	Oil-in-water emulsion
Oil phase	Mineral oil, castor oil, or medium-chain triglycerides
Ammonium halide	0.0005% to 0.1% w/w
Cationic ammonium halide	Cetalkonium chloride must be the sole ammonium halide
Surfactant	0.1% to 1% w/w
Permitted surfactants	Tyloxapol, poloxamer 188, tocopherol polyethylene glycol succinate, or mixtures

“Comprising” leaves the formulation open to additional excipients, buffers, tonicity agents, active ingredients, preservatives, and processing aids. It does not permit omission of any required claim element.

The claim does not require:

• Cyclosporine;
• Any active pharmaceutical ingredient;
• Ophthalmic administration;
• Dry-eye treatment;
• A positive zeta potential;
• A 100 to 500 nm droplet size;
• A particular pH;
• A particular oil concentration;
• A particular buffer;
• A particular manufacturing process.

This distinction is commercially important. A product may infringe claim 1 even if it is not marketed as a cyclosporine product or is not labeled for dry-eye disease.

How broad is claim 1 of U.S. Patent 9,956,289?

Claim 1 is broad in product purpose but constrained in composition.

A formulation falls within the literal scope of claim 1 if its oil-in-water emulsion includes at least one qualifying oil, cetalkonium chloride within the claimed range, and at least one qualifying surfactant within the claimed range. The oil may be mineral oil, castor oil, or medium-chain triglycerides. The claim does not require a combination of oils.

The phrase “cetalkonium chloride being the sole ammonium halide” creates a specific limitation. It excludes an emulsion containing cetalkonium chloride together with another ammonium halide, such as benzalkonium chloride, if that additional compound qualifies as an ammonium halide under the claim construction. It does not necessarily exclude other non-ammonium cationic or antimicrobial excipients.

The concentration ranges are central infringement limitations:

• Cetalkonium chloride: 0.0005% to 0.1% w/w;
• Qualifying surfactant or surfactant mixture: 0.1% to 1% w/w.

Unless the patent or prosecution history establishes a different construction, the endpoints are included. A formulation with 0.0005% cetalkonium chloride and 0.1% total qualifying surfactant would fall within the numerical ranges.

Which dependent claims materially narrow the patent?

The dependent claims divide into formulation, physical-property, therapeutic-use, medicament, process, and kit categories.

Claims	Subject matter	Commercial significance
2	Heavy and light mineral oil mixture	Targets a specific mineral-oil architecture
3	Buffering agents and/or tonicity agents	Broad excipient limitation
4	Mannitol as tonicity agent	Narrow ophthalmic formulation claim
5	Glycerol as tonicity agent	Narrow ophthalmic formulation claim
6	Positive zeta potential	Captures cationic emulsion behavior
7	Droplet size of 100 to 500 nm	Adds measurable particle-size limitation
8	Light and heavy mineral oil, tyloxapol, poloxamer 188, mannitol, cetalkonium chloride	Specific dry-eye formulation profile
9	Same core formulation with glycerol	Alternative tonicity formulation
10	Hypotonic relative to normal tears	Functional ophthalmic limitation
11	Suitable for ophthalmic use	Use-related narrowing
12	Less toxic than equivalent cetalkonium chloride solution	Comparative toxicity limitation
13	Active principle	Broad medicament formulation claim
14	Cyclosporine	Directly targets cyclosporine emulsions
15-16	Medicament and ophthalmic medicament	Product-category claims
17	Preparation of an ophthalmic dry-eye composition	Process claim
18	Two-emulsion dry-eye kit, including a cyclosporine emulsion	Combination-kit claim
19	Medium-chain triglycerides, tyloxapol, poloxamer 188, glycerol, cetalkonium chloride	Alternative specific formulation

Claims 8, 9, and 19 are likely the most commercially focused composition claims. They identify concrete excipient combinations rather than relying only on general category language.

What formulations are protected by U.S. Patent 9,956,289?

The patent covers several formulation families.

Mineral-oil emulsions

Claims 1 and 2 cover mineral-oil emulsions, including a formulation containing both light and heavy mineral oil. This is potentially important for products using mixed mineral-oil phases to achieve lubrication, spreading, or controlled droplet properties.

Castor-oil emulsions

Claim 1 also covers castor-oil emulsions, provided the formulation contains cetalkonium chloride and a qualifying surfactant in the claimed range. The claim does not require mineral oil if castor oil is used.

Medium-chain triglyceride emulsions

Claims 1 and 19 cover medium-chain triglyceride emulsions. Claim 19 narrows the formulation to medium-chain triglycerides with tyloxapol, poloxamer 188, glycerol, and cetalkonium chloride.

Cyclosporine emulsions

Claim 14 covers a formulation under claim 13 in which the active principle is cyclosporine. The claim does not specify cyclosporine concentration, so any concentration would need to be assessed against the other limitations inherited from claim 1.

The cyclosporine limitation does not convert the patent into a general cyclosporine patent. It covers only cyclosporine formulations that also satisfy the oil, cetalkonium chloride, and surfactant requirements of claim 1.

Ophthalmic emulsions

Claims 11 and 16 expressly address ophthalmic use. Claims 8 through 10 also have strong ophthalmic relevance because they recite conventional ophthalmic excipient choices and tear-related tonicity.

Claim 1 itself is not expressly limited to ophthalmic use. Its scope may therefore extend to non-ophthalmic emulsions if the other composition elements are met.

How should the positive zeta-potential limitation be interpreted?

Claim 6 requires a positive zeta potential. This limitation is technically important because cetalkonium chloride is a cationic surfactant that can impart a positive surface charge to oil droplets.

A product would need analytical evidence showing a positive zeta potential under defined test conditions. Measurement may vary with:

• pH;
• ionic strength;
• dilution medium;
• temperature;
• instrument and protocol;
• sample age;
• surfactant concentration.

A formulation can satisfy claim 1 without satisfying claim 6. Conversely, a formulation with a positive zeta potential does not infringe claim 6 unless it also satisfies every limitation of claim 1.

How does the droplet-size limitation affect infringement?

Claim 7 requires droplets measuring 100 to 500 nm. This is narrower than claim 1 and creates a measurable technical limitation.

The relevant question is whether the claimed range refers to average droplet diameter, a distribution range, a z-average, or another measurement convention. The patent specification and prosecution history would control that construction. Commercial products should be assessed using the same or a technically comparable method.

A formulation with an average droplet size of 250 nm may fall within claim 7. A formulation with a measured size of 80 nm or 700 nm would generally be outside the literal range, subject to the applicable measurement method and doctrine-of-equivalents analysis.

Does the patent require cyclosporine?

No. The broadest composition claim does not require cyclosporine.

Cyclosporine appears in claim 14 and in the second component of the kit in claim 18. A non-cyclosporine product may still infringe claims 1 through 12, 15 through 17, or 19 if it satisfies the relevant limitations.

This structure gives the patent broader platform coverage than a claim limited to a named active ingredient. It also means that a company cannot necessarily avoid the patent merely by replacing cyclosporine with another active ingredient.

What is the legal significance of the “less toxic” limitation?

Claim 12 requires an emulsion that is less toxic than a solution containing the same amount of cetalkonium chloride by weight.

This is a comparative limitation. Enforcement would likely require:

1. Identification of the relevant emulsion;
2. Identification of the comparison solution;
3. Matching cetalkonium chloride concentration;
4. A defined toxicity endpoint;
5. Testing under comparable conditions.

The claim may be difficult to evaluate without a reproducible assay and a clear definition of “toxicity.” It is narrower than claim 1 and is unlikely to be the primary enforcement claim unless the patent’s specification and prosecution record provide a well-defined test framework.

When does U.S. Patent 9,956,289 lose exclusivity?

U.S. Patent No. 9,956,289 issued on May 1, 2018. U.S. utility-patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments.[1]

The patent is associated with an international patent family originating from Novagali Pharma S.A. The family’s effective filing history places the nominal U.S. term in approximately 2029-2030 rather than 20 years from the 2018 issue date. The exact expiration date must be calculated from the patent’s term-adjustment data and the earliest effective nonprovisional or PCT filing date.

The patent does not receive an automatic five-year Hatch-Waxman patent-term extension merely because it relates to an ophthalmic formulation. A patent-term extension would require an eligible FDA-approved product and satisfaction of the statutory requirements in 35 U.S.C. § 156.[2]

What is the Orange Book status of U.S. Patent 9,956,289?

The patent is not inherently an Orange Book patent. Orange Book listing depends on an approved NDA, the NDA holder’s submission, and the patent’s relationship to the approved drug and labeling.[3]

The patent claims an emulsion platform and related formulation products. If the patented formulation is not the subject of an approved U.S. NDA, the patent would not ordinarily appear in the Orange Book. Cationorm-type products have primarily been associated with markets outside the U.S. and do not establish Orange Book listing by themselves.

The patent should therefore be distinguished from the Orange Book-listed patents historically associated with Restasis, Cequa, and other approved cyclosporine ophthalmic products. An Orange Book-listed cyclosporine patent may create separate regulatory and litigation barriers even when it does not claim the cetalkonium chloride emulsion covered by this patent.

Are there Paragraph IV challenges to U.S. Patent 9,956,289?

A Paragraph IV certification applies to a patent listed against an approved reference drug in the Orange Book. It is not a general challenge mechanism for any U.S. patent.

If U.S. Patent 9,956,289 is not listed against an approved reference product, an ANDA applicant would not ordinarily submit a Paragraph IV certification specifically against this patent. A generic or follow-on sponsor could still face ordinary patent litigation based on the patent, including an action under 35 U.S.C. § 271(e)(2) if the patent were properly listed against a relevant NDA.

The most likely challenge routes would be:

• Declaratory-judgment litigation;
• A direct infringement action after commercial launch;
• Inter partes review at the Patent Trial and Appeal Board;
• Invalidity defenses based on anticipation, obviousness, written description, enablement, indefiniteness, or double patenting;
• A non-infringement position based on excipient, concentration, droplet-size, or zeta-potential differences.

How strong is the patent estate for cetalkonium chloride ophthalmic emulsions?

The estate is strongest against products that use the following combination:

• Mineral oil or medium-chain triglycerides;
• Cetalkonium chloride at a low concentration;
• Tyloxapol and/or poloxamer 188;
• Ophthalmic emulsion technology;
• Mixed light and heavy mineral oil;
• Mannitol or glycerol;
• A positive zeta potential;
• Droplet sizes between 100 and 500 nm.

The estate is weaker against products that avoid one or more central claim elements, particularly:

• A non-oil-in-water delivery system;
• A different oil phase;
• A surfactant outside the claimed group;
• Total qualifying surfactant below 0.1% or above 1%;
• Cetalkonium chloride outside the claimed range;
• Another ammonium halide used in a way that defeats the “sole ammonium halide” limitation;
• A non-emulsion solution or suspension;
• A formulation with an incompatible particle-size profile.

The “comprising” language limits the effectiveness of simple excipient additions as a design-around. Adding a buffer, antioxidant, preservative, or active ingredient will not avoid infringement if the original claimed elements remain present.

What are the principal invalidity and enforcement issues?

Anticipation and obviousness

The central prior-art question is whether earlier ophthalmic emulsions disclosed the same combination of oil, cetalkonium chloride, and surfactant concentration. Generic disclosures of cationic emulsions may not anticipate the precise combination, but they may support an obviousness challenge when combined with prior art describing ophthalmic oil emulsions and the listed surfactants.

Written description and enablement

Claim 1 covers three oil categories, three surfactant categories, mixtures of surfactants, multiple dosage contexts, and a broad cetalkonium chloride range. The patent’s disclosure must support the full breadth of that genus.

Claim construction

Several terms may affect scope:

• “Oil-in-water emulsion”;
• “Sole ammonium halide”;
• “Surfactant”;
• “Positive zeta potential”;
• “Less toxic”;
• “Suitable for ophthalmic use”;
• “Hypotonic, relative to normal tears.”

The prosecution history may show whether the applicant narrowed the claims to overcome prior art. Such amendments can create estoppel against broad doctrine-of-equivalents positions.

Process-claim vulnerability

Claim 17 recites a method for preparing an ophthalmic composition for dry-eye treatment by preparing the emulsion. The claim may be narrower than the composition claims because infringement depends on the accused preparation process, not merely the sale of a finished composition. The dry-eye purpose may also affect claim construction.

Which companies and products create the main competitive overlap?

Product or platform	Company	Relationship to Patent 9,956,289
Cationorm-type cationic emulsion	Novagali/Santen	Closest technical and commercial overlap
Restasis, cyclosporine 0.05% emulsion	AbbVie/Allergan and generics	Cyclosporine overlap, but formulation overlap depends on cetalkonium chloride and claimed surfactants
Cequa, cyclosporine 0.09% nanomicellar solution	Sun Pharma	Likely differentiated by delivery system and formulation architecture
Ikervis, cyclosporine 0.1% emulsion	Santen	Cyclosporine and ophthalmic-emulsion overlap; exact excipient profile controls
Vevye, cyclosporine 0.1% solution	Novaliq	Different delivery technology and likely outside the claimed oil-in-water emulsion genus
Other artificial-tear emulsions	Multiple manufacturers	Risk depends on oil, cationic agent, surfactant, and concentration data

Restasis is associated with U.S. Patent No. 5,474,979, which claimed cyclosporine ophthalmic compositions and had a substantially earlier expiration timeline.[4] Cequa and Vevye use different formulation technologies and should not be treated as automatically overlapping with the patent at issue.

What generic launch risks exist?

A generic applicant seeking approval for a product that uses the claimed emulsion architecture could face a formulation patent risk even if the active ingredient is off-patent.

The highest-risk launch profile would include:

• An ophthalmic oil-in-water emulsion;
• Cetalkonium chloride within the claimed concentration range;
• Tyloxapol or poloxamer 188;
• Mineral oil or medium-chain triglycerides;
• A product positioned for dry-eye treatment;
• A droplet size within 100 to 500 nm;
• A positive zeta potential.

A lower-risk profile would use a non-emulsion formulation, omit cetalkonium chloride, use a different surfactant system, or move the relevant concentration outside the claimed ranges. Each design-around must be assessed against the full claim set and equivalents doctrine.

What licensing and ownership issues affect the patent?

Novagali Pharma developed cationic ophthalmic-emulsion technology and was acquired by Santen in 2011. Santen became the key commercial owner and developer associated with Novagali’s ophthalmic platform, including Cationorm-related products.[5]

The acquisition is commercially relevant because a patent assignment or license may affect enforcement rights, sublicensing, product rights, and litigation control. Ownership should be confirmed through the USPTO assignment record before a transaction, freedom-to-operate opinion, or enforcement assessment.

Key Takeaways

• Claim 1 is a broad platform claim covering oil-in-water emulsions with cetalkonium chloride and specified surfactants.
• Cyclosporine is not required by the broadest claim.
• The principal protected formulation variables are oil identity, cetalkonium chloride concentration, surfactant identity, and surfactant concentration.
• Claims 8, 9, and 19 are the most commercially specific formulation claims.
• Claims 6 and 7 add positive zeta potential and 100 to 500 nm droplet-size limitations.
• The patent’s nominal term runs approximately through 2029-2030, subject to official patent-term calculations.
• Orange Book and Paragraph IV relevance depends on linkage to an approved NDA.
• The closest commercial overlap is with Cationorm-type cationic ophthalmic emulsions.
• Restasis, Cequa, Ikervis, and Vevye require separate product-specific formulation and patent analyses.
• The strongest design-around paths involve changing the delivery system, oil phase, surfactant system, cetalkonium chloride concentration, or emulsion architecture.

FAQs

Can an emulsion infringe U.S. Patent 9,956,289 without containing cyclosporine?

Yes. Claim 1 does not require cyclosporine. Cyclosporine is required only for claim 14 and forms part of the kit structure in claim 18.

Does adding benzalkonium chloride avoid the patent?

Not necessarily. The claim requires cetalkonium chloride to be the sole ammonium halide. Adding another ammonium halide may avoid the literal “sole” limitation, but the chemical identity and claim construction must be evaluated.

Does using a surfactant other than tyloxapol or poloxamer 188 avoid infringement?

It may avoid claim 1 if the formulation does not contain tocopherol polyethylene glycol succinate or a mixture containing one of the listed surfactants. Other claims and equivalents analysis remain relevant.

Is a 600 nm ophthalmic emulsion outside claim 7?

It would generally be outside the literal 100 to 500 nm limitation of claim 7. It could still fall within claim 1 because claim 1 has no droplet-size limitation.

Can a product infringe the patent if it is sold as an artificial tear rather than a drug?

Potentially yes. Claim 1 is directed to the composition and does not require a drug label or dry-eye indication. Product classification does not alone determine infringement.

References

1. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation. https://www.uspto.gov/patents/laws/patent-term-calculator

2. U.S. Patent Act, 35 U.S.C. § 156.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files

4. U.S. Patent No. 5,474,979. (1995). Ophthalmic cyclosporin compositions. United States Patent and Trademark Office.

5. Santen Pharmaceutical Co., Ltd. (2011). Acquisition of Novagali Pharma and ophthalmic emulsion technology. Corporate transaction materials.

6. U.S. Patent No. 9,956,289. (2018). Oil-in-water emulsion comprising cetalkonium chloride. United States Patent and Trademark Office.

Drugs Protected by US Patent 9,956,289

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	VERKAZIA	cyclosporine	EMULSION;OPHTHALMIC	214965-001	Jun 23, 2021		RX	Yes	Yes	9,956,289		Y

International Family Members for US Patent 9,956,289

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2049079		PA2017003	Lithuania
European Patent Office	2049079		LUC00006	Luxembourg
European Patent Office	2049079		PA2017003,C2049079	Lithuania
European Patent Office	2049079		201740003	Slovenia
Australia	2007278141
Canada	2659322