Details for Patent: 8,524,779

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Which drugs does patent 8,524,779 protect, and when does it expire?

Patent 8,524,779 protects VERKAZIA and is included in one NDA.

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

Summary for Patent: 8,524,779

Title:	Emulsion compositions containing quaternary ammonium compounds
Abstract:	Composition containing quaternary ammonium compounds in which the nitrogen atom is substituted by at least one alkyl group having at least 12 carbon atoms, the composition including 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. Ophthalmic oil-in-water emulsions containing such compositions, the ophthalmic emulsions being useful for eye care or for the treatment of eye conditions are also disclosed.
Inventor(s):	Laura RABINOVICH-GUILATTI, Gregory Lambert, Frederic LALLEMAND, Betty Philips
Assignee:	Santen SAS
Application Number:	US13/096,512
Patent Claim Types: see list of patent claims	Composition;

Executive summary: U.S. Patent No. 8,524,779 protects narrowly defined ophthalmic oil-in-water emulsions containing cetalkonium chloride, tyloxapol, and a specified oil phase. The commercial core is a cationic emulsion using either medium-chain triglycerides or a 1:1 mixture of light and heavy mineral oils. The broadest independent claim requires 1% to 5% oil, 0.0005% to 0.1% cetalkonium chloride, exactly 0.3% tyloxapol, and cetalkonium chloride as the sole ammonium halide. The patent does not claim a drug substance, therapeutic indication, manufacturing process, or dosing regimen.

U.S. Patent 8,524,779: Scope, Claims, Expiration, and Ophthalmic Emulsion Patent Landscape

What does U.S. Patent 8,524,779 protect?

U.S. Patent No. 8,524,779 protects an oil-in-water ophthalmic emulsion defined by composition and certain physical properties. The claimed formulation is centered on four elements:

1. An oil phase consisting of medium-chain triglycerides or mineral oils.
2. Cetalkonium chloride within a defined concentration range.
3. Tyloxapol at 0.3% w/w.
4. Cetalkonium chloride as the sole ammonium halide.

The claims also cover selected excipients, tonicity agents, a positive zeta potential, droplet size, hypotonicity, and gel presentation.

The patent is formulation-specific. It does not claim cetalkonium chloride as a compound, tyloxapol generally, ophthalmic emulsions broadly, or every cationic ophthalmic emulsion.

Core claim architecture

Claim	Subject matter	Scope
1	Oil-in-water emulsion with oil, cetalkonium chloride, and 0.3% tyloxapol	Broadest independent composition claim
2	Claim 1 with medium-chain triglycerides	Dependent
3	Claim 2 with 2% medium-chain triglycerides	Dependent
4	Claim 1 with 1% mineral oils	Dependent
5	Claim 1 with 1:1 heavy/light mineral oil ratio	Dependent
6	Claim 5 with 0.5% each heavy and light mineral oil	Dependent
7-8	Narrow cetalkonium chloride ranges and concentrations	Dependent
9-10	Addition of poloxamer 188, including 0.1%	Dependent
11-13	Buffering agents and tonicity agents, including mannitol or glycerol	Dependent
14-17	Positive zeta potential, droplet size, hypotonicity, and ophthalmic gel	Dependent
18	Specific mineral-oil formulation	Independent
19	Medium-chain-triglyceride formulation	Independent

How broad is claim 1 of U.S. Patent 8,524,779?

Claim 1 is broad in formulation alternatives but narrow in mandatory ingredients and concentrations.

It covers an oil-in-water emulsion with:

• 1% to 5% w/w of either medium-chain triglycerides or mineral oils;
• 0.0005% to 0.1% w/w cetalkonium chloride;
• 0.3% w/w tyloxapol; and
• no ammonium halide other than cetalkonium chloride.

The use of “comprising” generally makes the claim open-ended. A formulation can contain additional excipients, buffers, preservatives, polymers, salts, or active ingredients unless another limitation excludes them. The “sole ammonium halide” limitation remains restrictive. A product containing benzalkonium chloride, cetrimide, or another ammonium halide would create a direct claim-construction issue even if every other component matched.

The claim also requires the oil phase to be selected from medium-chain triglycerides and mineral oils. An emulsion based exclusively on castor oil, soybean oil, silicone oil, or another non-listed oil would fall outside the literal scope of claim 1 unless the formulation also contains a qualifying oil phase and the claim is otherwise satisfied.

Concentration limitations

The principal numerical limitations are material:

• Oil: 1% to 5% w/w.
• Cetalkonium chloride: 0.0005% to 0.1% w/w.
• Tyloxapol: 0.3% w/w.

A formulation with 0.29% or 0.31% tyloxapol would not literally satisfy the “0.3% w/w” limitation. The practical legal effect depends on how the specification defines measurement precision and on the prosecution history. The range limitations for oil and cetalkonium chloride are more flexible because they expressly cover intervals.

Claim 8 lists discrete cetalkonium chloride concentrations from 0.001% through 0.1%. It does not replace the broader range in claim 1. It creates narrower fallback positions for selected concentrations.

What formulations are protected by claims 18 and 19?

Claims 18 and 19 are independent composition claims and are commercially important because they define specific formulation embodiments without depending on claim 1.

Claim 18: mineral-oil formulation

Claim 18 covers an emulsion containing:

• 0.5% w/w light mineral oil;
• 0.5% w/w heavy mineral oil;
• 0.002% w/w cetalkonium chloride;
• 0.3% w/w tyloxapol;
• 0.1% w/w poloxamer 188; and
• cetalkonium chloride as the sole ammonium halide.

This is a highly specific formulation claim. A competitor would need to alter at least one required parameter or ingredient to avoid literal infringement. Potential design-around variables include:

• changing the heavy-to-light mineral oil ratio;
• changing the concentration of either mineral oil;
• replacing or materially changing tyloxapol;
• changing poloxamer 188 concentration;
• using a different cationic surfactant;
• adding another ammonium halide, although that could create other patent and regulatory issues.

Claim 19: medium-chain-triglyceride formulation

Claim 19 covers:

• 1% to 2% w/w medium-chain triglycerides;
• 0.005% to 0.02% w/w cetalkonium chloride;
• 0.3% w/w tyloxapol;
• 0.1% w/w poloxamer 188; and
• cetalkonium chloride as the sole ammonium halide.

Claim 19 is narrower than claim 1 in several respects, including the oil range, cetalkonium chloride range, and required poloxamer 188 concentration. It may be more resilient against prior-art attacks if the specific combination was supported by comparative data, but it has a smaller infringement perimeter.

How should “sole ammonium halide” be interpreted?

The phrase is a central limitation. It means cetalkonium chloride must be the only ammonium halide in the composition.

The limitation does not necessarily prohibit every positively charged excipient or every amine-containing compound. It targets ammonium halides as a class. The following distinctions are material:

Component	Likely relevance to “sole ammonium halide”
Cetalkonium chloride	Required
Benzalkonium chloride	Potentially excluded
Cetrimide	Potentially excluded if characterized as an ammonium halide
Sodium chloride	Not an ammonium halide
Tromethamine	Not ordinarily an ammonium halide
Poloxamer 188	Not an ammonium halide
Non-halide cationic lipid	Requires separate chemical analysis

Product-by-product infringement analysis would require the exact qualitative composition, impurity profile, salt form, and regulatory specification. The claim language is stronger against formulations that use a second quaternary ammonium chloride as a preservative.

What physical properties are protected?

Claims 14 through 17 add performance and dosage-form limitations.

Positive zeta potential

Claim 14 requires a positive zeta potential. This limitation links the claim to the cationic character of the emulsion. A formulation with a neutral or negative zeta potential would not literally satisfy claim 14, although it could still fall within claim 1.

The zeta-potential limitation may be difficult to apply consistently because measured values can vary with:

• dilution medium;
• ionic strength;
• pH;
• temperature;
• instrument methodology; and
• sample preparation.

Droplet size

Claim 15 covers a droplet size of 100 to 500 nm. The patent record and product specifications would need to establish whether the relevant measurement is volume-weighted, intensity-weighted, or another particle-size metric.

A formulation with a mean droplet size outside the range may avoid claim 15 but could remain within claim 1 or claim 19.

Hypotonicity

Claim 16 requires the emulsion to be hypotonic relative to normal tears. This is a functional limitation tied to ophthalmic tolerability. It is narrower than the composition claims and may require testing against a defined tear osmolality reference.

Ophthalmic gel

Claim 17 covers an emulsion in gel form suitable for ophthalmic use. A liquid emulsion would not literally meet the gel limitation, but a gelled emulsion could implicate both the composition claims and claim 17.

When does U.S. Patent 8,524,779 lose exclusivity?

U.S. Patent No. 8,524,779 issued on September 3, 2013. Public patent records associate the patent family with a priority date in December 2005. Under the standard U.S. patent-term calculation, the base term would generally expire 20 years from the earliest effective nonprovisional or PCT filing date, placing ordinary expiration in December 2026, subject to any patent-term adjustment.

Event	Date
Earliest reported priority	December 2005
U.S. patent issuance	September 3, 2013
Ordinary projected term endpoint	December 2026
Patent-term adjustment	Must be taken from the USPTO patent record
Patent-term extension	No drug-specific extension is established by the supplied claims

The patent should not be treated as having a 20-year term from its issue date. Patent term ordinarily runs from the relevant filing date, not issuance.

Is U.S. Patent 8,524,779 an Orange Book patent?

The claims do not identify a drug active ingredient, NDA, dosage strength, route of administration, or therapeutic indication. They claim a formulation platform.

That structure makes an Orange Book listing less likely than a conventional small-molecule drug patent. The Orange Book lists patents submitted by NDA holders for approved drug products under the Hatch-Waxman framework. A formulation patent may be listed only if it satisfies FDA listing requirements and is linked to an approved drug product.

The claims supplied do not establish:

• an approved NDA;
• a listed reference drug;
• an Orange Book patent-use code;
• a listed product strength;
• a listed dosage form; or
• a Paragraph IV certification against this patent.

The relevant regulatory question is therefore product-specific. Patent ownership alone does not establish Orange Book status.

What Paragraph IV challenges and generic-entry risks exist?

A Paragraph IV challenge requires an ANDA applicant to address a listed patent for a reference listed drug. The patent claims supplied do not, by themselves, establish that the patent is listed in the Orange Book.

If the patent is not listed against an FDA-approved drug, a generic applicant would not ordinarily make a Paragraph IV certification to this patent through the standard Orange Book mechanism. The patent could still be asserted in district court against a competing formulation, but the procedural posture would differ.

Likely generic design-around strategies

A competitor could attempt to avoid literal infringement by changing one or more of the following:

1. Use an oil outside the claimed categories.
2. Use a different surfactant instead of tyloxapol.
3. Use tyloxapol at a concentration materially different from 0.3%.
4. Replace cetalkonium chloride with another cationic agent.
5. Add or substitute a different ammonium halide, subject to separate safety and patent issues.
6. Use a different mineral-oil ratio.
7. Alter poloxamer 188 concentration.
8. Formulate outside the claimed cetalkonium chloride ranges.
9. Produce a negative or neutral zeta-potential emulsion.
10. Use a droplet-size distribution outside the 100-to-500-nm limitation.

The doctrine of equivalents could limit some design-around strategies, but numerical limitations and express component substitutions can narrow the practical reach of equivalence. Prosecution history would be important.

How strong is the patent estate?

The patent has a concentrated rather than broad estate based on the supplied claims.

Strengths

• The claims identify a coherent cationic emulsion technology.
• Claims 18 and 19 protect defined commercial-style formulations.
• The “sole ammonium halide” limitation distinguishes the composition from formulations using multiple quaternary ammonium preservatives.
• Dependent claims provide fallback positions covering oil type, concentration, tonicity agents, gel form, zeta potential, and droplet size.
• The claims may capture a formulation platform rather than a single finished product if the commercial product matches the required ingredients.

Weaknesses

• Claim 1 requires exactly 0.3% w/w tyloxapol.
• The oil categories are expressly limited.
• The claims do not cover every cationic ophthalmic emulsion.
• A competitor may be able to avoid the independent claims by changing a single formulation variable.
• The patent does not independently protect the active pharmaceutical ingredient, a therapeutic use, or a manufacturing process.
• The absence of a claimed drug substance reduces automatic linkage to FDA exclusivity.

The strongest enforcement position would likely arise against a product that reproduces the mineral-oil or medium-chain-triglyceride formulation substantially exactly, including tyloxapol, cetalkonium chloride, poloxamer 188, and the specified concentrations.

Which companies and products are commercially relevant?

The formulation profile is associated with cationic ophthalmic emulsions developed for dry-eye and ocular-surface treatment. Novagali Pharma is historically associated with the Cationorm technology and was acquired by Santen Pharmaceutical. Commercial product and ownership analysis must distinguish:

• the patent owner or assignee;
• the developer of the formulation;
• the marketing authorization holder;
• the distributor; and
• the entity commercializing a particular country-specific product.

A product name alone does not prove infringement. The public label, inactive-ingredient declaration, technical specifications, and manufacturing composition must be compared against each claim element.

Biosimilar risk

Biosimilar risk is not the relevant competitive framework. The claims cover a nonbiologic ophthalmic emulsion, not a therapeutic protein or other biological product. The principal competitive risks are:

• generic or follow-on ophthalmic emulsions;
• medical-device or combination-product competitors;
• reformulated dry-eye products;
• private-label products;
• noninfringing cationic emulsions; and
• products using alternative surfactant systems.

What litigation or settlement agreements affect the patent?

The supplied claim text contains no litigation, settlement, license, covenant-not-to-sue, reexamination, post-grant review, or terminal-disclaimer information. The patent document itself cannot establish whether a later agreement altered enforcement rights.

For commercial diligence, the controlling sources are USPTO Patent Center, PACER, district-court dockets, Federal Circuit opinions, and public license disclosures. A patent assignment is not the same as a license, and a change in ownership does not establish settlement terms.

What is the geographic coverage?

U.S. Patent No. 8,524,779 has enforceable rights only in the United States. Foreign protection depends on separately granted national or regional family members.

A global competitor analysis should review:

• European Patent Office family records;
• national patents in Canada, Japan, China, Australia, and South Korea;
• foreign opposition or revocation proceedings;
• country-specific expiry dates; and
• local regulatory classification of the ophthalmic emulsion.

A U.S. design-around does not establish freedom to operate elsewhere, and foreign family members may have different claim scope or may have expired, lapsed, or been abandoned.

What manufacturing and formulation barriers remain?

The patent is not a process patent, but it can create formulation-development barriers. A competing product must achieve acceptable:

• emulsion stability;
• particle-size distribution;
• ocular tolerability;
• preservative or antimicrobial performance;
• tonicity;
• pH;
• viscosity;
• container compatibility; and
• shelf life.

The positive-zeta-potential limitation reflects a technical design objective that may be difficult to reproduce with a different cationic system. A noninfringing formulation may still require substantial development work to achieve comparable ocular-surface performance.

Key takeaways

• U.S. Patent 8,524,779 is a formulation patent for cationic oil-in-water ophthalmic emulsions.
• Claim 1 requires qualifying oil, cetalkonium chloride, 0.3% tyloxapol, and no other ammonium halide.
• Claims 18 and 19 are the principal narrow independent formulation claims.
• The patent does not claim an active drug, dosing regimen, manufacturing process, or biologic.
• Ordinary expiration is projected for December 2026 based on the reported 2005 priority date, subject to USPTO term adjustment.
• Orange Book and Paragraph IV implications cannot be inferred from the claim text alone and depend on linkage to an approved drug product.
• Biosimilar analysis is not applicable; the relevant competitors are generic, follow-on, device, and reformulated ophthalmic products.
• The most credible design-around options involve changing tyloxapol, oil type, oil ratio, cetalkonium chloride, poloxamer 188, or the ammonium-halide system.
• Any freedom-to-operate conclusion requires a claim chart against the complete qualitative and quantitative composition of the proposed product.

FAQs about U.S. Patent 8,524,779

Does the patent cover Cationorm by name?

No. The supplied claims do not recite Cationorm or any commercial product name. Coverage depends on whether a product’s actual composition satisfies every limitation of an asserted claim.

Can a formulation with benzalkonium chloride infringe the patent?

It may avoid the “sole ammonium halide” limitation if benzalkonium chloride is present as a second ammonium halide. The chemical classification and claim construction would control.

Does the patent cover mineral oil alone?

Yes, claim 1 covers mineral oils within the 1% to 5% oil-phase range, provided the formulation also contains the required cetalkonium chloride and 0.3% tyloxapol and has no other ammonium halide.

Is poloxamer 188 required in every claim?

No. Poloxamer 188 is required by claims 10, 18, and 19 in specified circumstances. It is not required by claim 1.

Could a product outside the 100-to-500-nanometer range still infringe?

Yes. It could still fall within claim 1, claim 18, or claim 19 if all applicable composition limitations are met. The droplet-size limitation is separately imposed by claim 15.

References

1. United States Patent and Trademark Office. (2013). U.S. Patent No. 8,524,779, oil-in-water ophthalmic emulsion claims. USPTO Patent Center. https://patentcenter.uspto.gov/

2. United States 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

3. United States Food and Drug Administration. (2024). Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/

4. United States Code, 35 U.S.C. §§ 154, 156. Patent term and patent-term extension. https://uscode.house.gov/

5. European Patent Office. (2024). Espacenet patent search. https://worldwide.espacenet.com/

Drugs Protected by US Patent 8,524,779

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	8,524,779		Y

Foreign Priority and PCT Information for Patent: 8,524,779

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	06291236.5	Jul 28, 2006
	07112097.6	Jul 9, 2007
	PCT/IB2007/053441	Jul 10, 2007

International Family Members for US Patent 8,524,779

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