Details for Patent: 9,132,071

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Which drugs does patent 9,132,071 protect, and when does it expire?

Patent 9,132,071 protects VERKAZIA and is included in one NDA.

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

Summary for Patent: 9,132,071

Title:	Compositions containing quaternary ammonium compounds
Abstract:	Compositions containing quaternary ammonium compounds in which the nitrogen atom is substituted by at least one alkyl group having at least 12 carbon atoms, where 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. Ophthalmic oil-in-water emulsions containing such compositions, and the ophthalmic emulsions being are useful for eye care or for the treatment of eye conditions.
Inventor(s):	Laura Rabinovich-Guilatt, Gregory Lambert, Frederic LALLEMAND, Betty Philips
Assignee:	Santen SAS
Application Number:	US12/010,778
Patent Claim Types: see list of patent claims	Compound;

United States Patent 9,132,071: Claim Scope, Expiration, and Emulsion Patent Landscape

U.S. Patent No. 9,132,071 protects cationic oil-in-water emulsions that contain a defined concentration of C12-C16 alkyl dimethyl- or trimethyl-benzyl ammonium halide, with a minimum C16 content, a positive droplet zeta potential of at least +14.3 mV, and stability for at least three months. Cetalkonium chloride is the principal disclosed embodiment.

The broadest commercial relevance is in ophthalmic emulsions containing cetalkonium chloride, an oil phase, water, and one or more surfactants. The patent does not claim a particular marketed drug product by name. It claims a formulation architecture and measurable physicochemical properties.

What patent is U.S. Patent 9,132,071?

U.S. Patent 9,132,071 is directed to emulsions containing cationic quaternary ammonium compounds, particularly cetalkonium chloride, also known as C16-alkyl dimethylbenzyl ammonium chloride.

Field	Analysis
Patent	U.S. Patent No. 9,132,071
Core technology	Cationic oil-in-water emulsions
Principal cationic agent	Cetalkonium chloride
Claimed concentration	0.0005% to 0.1% by weight of total emulsion
C16 content	At least 20% by weight of the ammonium halide; dependent claims increase this to 80%, about 90%, or about 95%
Required droplet charge	Zeta potential of at least +14.3 mV
Required physical property	Stability for at least three months after emulsification
Key dosage form	Ophthalmic oil-in-water emulsion
Expressly listed active substances	Riluzole, fusidic acid, latanoprost, loratadine, tacrolimus, naphazoline, and ketanserine
Principal commercial implication	Protection of cationic ophthalmic emulsion platforms rather than a single active ingredient

The patent is formulation-focused. It does not claim cetalkonium chloride as a chemical compound, nor does it broadly claim every ophthalmic use of cetalkonium chloride.

What does claim 1 of U.S. Patent 9,132,071 cover?

Claim 1 is the broadest independent composition claim. An accused formulation must satisfy all material limitations:

1. It must be an emulsion.
2. It must contain an aqueous phase comprising water.
3. It must contain 0.0005% to 0.1% by weight of a C12-C16 alkyl dimethyl- or trimethyl-benzyl ammonium halide.
4. At least 20% by weight of that ammonium halide must be the C16 species.
5. The emulsion droplets must have a zeta potential of at least +14.3 mV.
6. The emulsion must remain stable for at least three months after emulsification.

The claim is therefore narrower than a conventional composition claim covering any emulsion with cetalkonium chloride. The cationic agent concentration, C16 fraction, zeta potential, and stability requirement are cumulative limitations.

How broad is the chemical genus?

The claimed genus covers C12, C13, C14, C15, and C16 alkyl groups when attached to the specified dimethyl- or trimethyl-benzyl ammonium structure. The claim also allows a mixture of homologues, provided that at least 20% by weight of the ammonium halide is the C16 species.

Cetalkonium chloride is the most commercially recognizable example. It is primarily the C16 homologue, making it capable of satisfying the C16-content limitation without relying on a mixed C12-C16 distribution.

A formulation containing a quaternary ammonium compound outside the claimed structural class would not literally satisfy claim 1. Examples potentially outside the literal genus include benzalkonium formulations dominated by homologues outside the C12-C16 range, non-benzyl quaternary ammonium compounds, and cationic surfactants lacking the claimed alkyl dimethyl- or trimethyl-benzyl structure.

Which dependent claims add the most commercial value?

Claims 2 through 14 narrow the broad composition claim. Claims 15 through 19 create a separate ophthalmic-emulsion claim set.

Claims	Added limitation	Commercial significance
2	Oil-in-water emulsion	Targets the dominant ophthalmic emulsion architecture
3	At least 80% C16 ammonium halide	Narrows the composition toward cetalkonium-rich products
4	About 90% C16	Further narrows homologue composition
5	About 95% C16	Closest dependent formulation to high-purity C16 material
6	Cetalkonium chloride	Directly identifies the principal commercial compound
7	0.002% to about 0.01% concentration	Covers typical low-level preservative or cationic-surfactant concentrations
8-9	Defined oils, including medium-chain triglycerides	Covers common emulsion vehicles
10	Defined surfactants	Captures formulation systems used to stabilize droplets
11	Osmotic agent	Relevant to ophthalmic tolerability and tonicity
12	Additional cationic agent	Allows multi-cationic formulations
13	Claimed ammonium halide is the only cationic agent	Narrows toward simpler cationic systems
14	Listed active substances	Links the platform to specific therapeutic payloads
15	Ophthalmic oil-in-water emulsion with oil phase and surfactant	Independent ophthalmic formulation claim
16	At least 80% C16 content	Narrows claim 15 toward cetalkonium-rich emulsions
17	Cetalkonium chloride	Direct cetalkonium ophthalmic claim
18	Defined oil classes	Narrows the ophthalmic vehicle
19	Aqueous phase comprising at least 99.9% water	Covers highly aqueous ophthalmic systems

Claims 6 and 17 are particularly important for freedom-to-operate analysis because they identify cetalkonium chloride directly. Claims 9, 10, 14, 18, and 19 are narrower and may be easier to design around, depending on the product formulation.

What formulations are protected by the patent?

The strongest apparent coverage is for an ophthalmic oil-in-water emulsion with the following profile:

• Water-rich aqueous phase.
• Oil phase containing medium-chain triglycerides or another listed oil.
• Cetalkonium chloride at approximately 0.002% to 0.01%.
• One or more listed surfactants.
• Positive droplet zeta potential of at least +14.3 mV.
• Stability for at least three months.
• Optional active ingredient such as latanoprost, tacrolimus, fusidic acid, or naphazoline.

The patent does not require every dependent feature simultaneously. A formulation containing cetalkonium chloride, for example, may fall within claim 1 or claim 15 even if it does not contain medium-chain triglycerides, an osmotic agent, or one of the listed active ingredients, provided the independent-claim limitations are met.

Are formulations with only cetalkonium chloride covered?

Potentially, yes. Claim 13 expressly covers an emulsion in which the C12-C16 ammonium halide is the only cationic agent. This does not mean cetalkonium chloride must be the only surfactant or the only excipient. The limitation concerns cationic agents, not all formulation components.

A product can therefore contain nonionic or anionic surfactants and still potentially satisfy claim 13, unless those ingredients are interpreted or demonstrated to have cationic activity.

How important is the zeta-potential limitation?

The zeta-potential limitation is central to both infringement and validity analysis. The threshold is at least +14.3 mV, which requires a positive droplet surface charge above a defined numerical level.

A formulation with cetalkonium chloride at the claimed concentration would not automatically infringe. The product must also produce droplets with the required measured charge.

Key technical issues

The following variables can affect zeta-potential measurements:

• Measurement medium and ionic strength.
• pH.
• Dilution procedure.
• Temperature.
• Electrophoretic-light-scattering instrument.
• Droplet-size distribution.
• Sampling location and timing.
• Presence of other charged excipients.
• Whether the measurement is made before or after dilution for administration.

The patent claim does not state the entire measurement protocol in the claim text supplied. That creates potential disputes over reproducibility, claim construction, and whether a product meets the threshold under a legally appropriate test method.

For invalidity analysis, the threshold may also be relevant to enablement, written description, indefiniteness, and anticipation. A prior-art emulsion with cetalkonium chloride would not necessarily anticipate the patent unless the prior art disclosed, expressly or inherently, the claimed zeta potential and three-month stability.

What does the three-month stability limitation require?

The stability limitation requires that the emulsion remain stable for at least three months after emulsification. Stability is not defined in the supplied claim language by a specific endpoint such as droplet-size growth, phase separation, creaming, coalescence, active-content loss, or zeta-potential retention.

That omission makes the stability limitation commercially significant and legally contestable. An infringement analysis would need to determine:

• The storage temperature.
• Whether stability is assessed in the original container.
• The acceptable level of phase separation.
• Whether chemical and physical stability are both required.
• Whether the formulation must remain stable during ordinary storage or under accelerated conditions.
• Whether stability is measured from manufacture, laboratory emulsification, or another defined event.

A competitor may seek to avoid literal infringement by showing that its formulation does not remain stable for the claimed period under the applicable test. That approach carries regulatory and commercial consequences because inadequate emulsion stability could also impair product quality.

What is the scope of the ophthalmic claims?

Claims 15 through 19 create a separate ophthalmic claim family. Claim 15 requires:

• An aqueous phase comprising water.
• 0.0005% to 0.1% ammonium halide.
• At least 20% C16 content.
• An oily phase.
• A surfactant.
• Droplet zeta potential of at least +14.3 mV.
• Stability for at least three months.

The ophthalmic claims are narrower than claim 1 because they require an oily phase and a surfactant. They may nevertheless be commercially stronger because most relevant products would be ophthalmic oil-in-water emulsions rather than generic emulsions for unrelated routes of administration.

Claim 19 is especially narrow. It requires an aqueous phase comprising at least 99.9% water. A formulation with a material amount of water-miscible solvent, polyol, buffer, or other dissolved excipient could raise a question under this limitation, depending on whether the 99.9% figure is measured by weight and how the aqueous phase is defined.

When does U.S. Patent 9,132,071 lose exclusivity?

The patent appears to derive from a priority filing in December 2005 and a U.S. nonprovisional filing in December 2006. Under the standard U.S. patent-term framework, the base term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and other statutory modifications.[1]

On that basis, the ordinary expiration is expected to fall in December 2026, subject to the official patent-term calculation. A precise expiration date requires the USPTO Patent Center term data, including any patent-term adjustment and terminal disclaimer information.

Event	Approximate timing
Earliest priority	December 2005
U.S. filing	December 2006
U.S. patent grant	2015
Expected base term endpoint	December 2026
Potential adjustment	Must be confirmed from USPTO records

No Hatch-Waxman patent-term extension should be assumed merely from the patent number. Patent-term extension under 35 U.S.C. §156 depends on a qualifying regulatory approval and a specific extension application. A formulation patent also may not be listed in the FDA Orange Book if it is not tied to an approved drug application.

What is the Orange Book status of U.S. Patent 9,132,071?

A patent number alone does not establish Orange Book listing. The FDA Orange Book generally lists patents submitted by an approved new drug application holder for an approved drug product, including qualifying drug substance, drug product, and method-of-use patents.[2]

U.S. Patent 9,132,071 is a formulation patent covering a broad emulsion platform. Its Orange Book relevance depends on whether the patent was submitted for a specific approved drug application and accepted by FDA for listing.

The patent should not be treated as Orange Book-listed without a product-specific FDA record. If it is not listed, an abbreviated new drug applicant would not face a Paragraph IV certification directed to this patent through the Orange Book process, although the patent could still support a conventional infringement action.

Are Paragraph IV challenges likely?

A Paragraph IV challenge is relevant only if the patent is listed in the Orange Book against an approved reference product. If listed, an ANDA applicant could certify that the patent is invalid, unenforceable, or would not be infringed by the proposed product.[3]

The claims create several potential Paragraph IV strategies:

1. No literal match to zeta potential. The proposed product could argue that its droplets have a zeta potential below +14.3 mV.
2. Different cationic agent. A formulation could use a compound outside the C12-C16 dimethyl- or trimethyl-benzyl ammonium genus.
3. Lower C16 content. A mixed homolog composition could contain less than 20% C16 material.
4. Concentration design-around. The cationic agent could fall below 0.0005% or above 0.1%, subject to product-performance and safety constraints.
5. Stability distinction. The proposed product could challenge the three-month stability limitation.
6. Non-oily or non-surfactant system. This is more relevant to claims 15 through 19 than to claim 1.

The strongest invalidity theories would likely focus on prior art disclosing cationic ophthalmic emulsions and whether the claimed zeta-potential and stability limitations were expressly disclosed or inherently present.

What prior-art and patent-family issues matter most?

The relevant prior-art field includes:

• Cationic ophthalmic emulsions.
• Benzalkonium chloride and cetalkonium chloride formulations.
• Emulsion stabilizers and droplet-charge control.
• Oil-in-water ophthalmic delivery systems.
• Medium-chain triglyceride vehicles.
• Cationic surfactants used to improve corneal or ocular-surface residence.
• Formulations of latanoprost, tacrolimus, fusidic acid, and other listed actives.

The patent’s likely inventive distinction is not the general use of an emulsion or the mere presence of a quaternary ammonium compound. The narrower distinction is the relationship among:

• C16 homologue content.
• Low cationic-agent concentration.
• Positive zeta potential.
• Three-month stability.
• Ophthalmic oil-in-water structure.

A patentability challenge would therefore need to address the combination, not simply identify earlier emulsions containing one of the ingredients.

Which companies and products are relevant to the competitive landscape?

The closest competitive landscape is the cationic ophthalmic-emulsion sector. Relevant companies and products include Santen’s cationic cyclosporine emulsion technology, Novagali-derived ophthalmic emulsion platforms, and manufacturers of ophthalmic products using benzalkonium chloride or related quaternary ammonium preservatives.

The presence of a cationic emulsion in a competing product does not establish infringement. The product must meet the concentration, C16-content, zeta-potential, oil-phase, surfactant, and stability limitations applicable to the asserted claim.

Product or platform category	Relevance to U.S. 9,132,071
Cationic cyclosporine emulsions	Potentially relevant formulation technology; active ingredient differs from the listed actives
Cetalkonium-containing ophthalmic emulsions	Highest technical relevance
Benzalkonium-preserved eye drops	Relevant only if the chemical composition and emulsion properties fall within the claims
Conventional anionic or nonionic emulsions	Generally lower risk absent the claimed cationic agent and positive zeta potential
Lipid-based ophthalmic products	Relevant if they are oil-in-water emulsions with the claimed cationic profile

Does the patent create biosimilar risk?

No conventional biosimilar risk arises from this patent. Biosimilars are biologic products regulated under the Public Health Service Act. U.S. Patent 9,132,071 claims a non-biologic emulsion formulation.

The relevant exposure is generic or 505(b)(2) competition, not biosimilar entry. A drug product containing one of the listed active substances could face a formulation patent issue through an ANDA, a 505(b)(2) application, or a conventional patent-infringement dispute, depending on the reference product and regulatory pathway.

What generic launch scenarios exist?

Scenario 1: Product avoids cetalkonium chloride

A generic manufacturer could use a different emulsion stabilizer or cationic agent. This is the cleanest design-around if the alternative does not fall within the claimed chemical genus.

Scenario 2: Product uses cetalkonium chloride but controls zeta potential

The manufacturer could attempt to formulate below +14.3 mV. This approach must be supported by reproducible analytical testing and cannot compromise emulsion performance.

Scenario 3: Product uses a different homologue distribution

A formulation containing less than 20% C16 material may avoid claim 1, but it would also need to avoid the broader structural and functional limitations under the doctrine of equivalents.

Scenario 4: Product changes the dosage-form architecture

A non-emulsion, water-in-oil emulsion, suspension, solution, or non-oily ophthalmic system could avoid claims directed to the claimed emulsion structure. Claims 1 and 15 should be analyzed separately because claim 1 is not expressly limited to oil-in-water or ophthalmic use.

Scenario 5: Product launches after patent expiry

If the patent expires in December 2026 without a qualifying extension, post-expiry products would not face infringement liability from this patent. Other family members, continuation patents, formulation patents, and regulatory exclusivities could still affect launch timing.

How strong is the patent estate?

The patent has meaningful claim breadth but several measurable limitations.

Strengths

• Covers a formulation platform rather than one narrow commercial recipe.
• Identifies cetalkonium chloride directly.
• Captures low concentrations likely to be technically and commercially useful.
• Uses zeta potential as a product-defining parameter.
• Includes both general emulsion and ophthalmic-emulsion claims.
• Covers multiple oils, surfactants, and active substances.

Weaknesses

• Zeta potential can be measurement-sensitive.
• The three-month stability limitation may require detailed claim construction.
• The C12-C16 chemical genus may be avoided through alternative cationic agents.
• The claims do not cover every cetalkonium formulation.
• The patent term is approaching its expected endpoint.
• Orange Book leverage depends on product-specific listing, not the patent grant alone.

Overall, the patent is strongest against a cetalkonium-containing ophthalmic oil-in-water emulsion that has a strongly positive droplet charge and documented three-month stability. It is weaker against non-emulsion products, formulations using different cationic chemistries, and products engineered below the zeta-potential threshold.

What patent litigation or settlement agreements affect this patent?

The supplied information does not establish a specific infringement action, Paragraph IV case, settlement agreement, or license involving U.S. Patent 9,132,071. No litigation or settlement should be attributed to the patent without a docket, FDA listing, or public agreement identifying the patent number.

Licensing is commercially relevant because ophthalmic emulsion technologies are often transferred with broader platform rights, manufacturing know-how, formulation data, and related patent families. A license covering a product or technology platform may extend beyond the claims of U.S. 9,132,071 and may include foreign counterparts or unexpired continuation patents.

What geographic coverage does the patent provide?

U.S. Patent 9,132,071 provides rights in the United States only. Parallel protection, if any, must be assessed through the corresponding PCT and national-stage applications.

The commercial assessment should separate:

• U.S. composition claims.
• European or other national counterparts.
• Patent-term differences by jurisdiction.
• National validation and maintenance status.
• Continuation or divisional applications.
• Foreign claims directed to methods of treatment, manufacturing, or specific ophthalmic products.

A U.S. design-around does not establish freedom to operate in Europe, Canada, Japan, China, or other markets.

Key Takeaways

• U.S. Patent 9,132,071 protects cationic emulsions with a defined C12-C16 benzyl ammonium halide profile.
• Cetalkonium chloride is the principal claimed commercial embodiment.
• The core technical barriers are a concentration of 0.0005% to 0.1%, at least 20% C16 content, zeta potential of at least +14.3 mV, and three-month stability.
• Claims 15 through 19 target ophthalmic oil-in-water emulsions with an oil phase and surfactant.
• Claims 6 and 17 are the most direct cetalkonium chloride claims.
• The patent is not a biosimilar patent. Generic and 505(b)(2) pathways are the relevant competitive routes.
• Orange Book significance depends on listing against a specific approved drug application.
• The expected base patent term appears to end in December 2026, subject to USPTO term data and any adjustment or extension.
• The most practical design-arounds involve changing the cationic agent, reducing C16 content, keeping zeta potential below the threshold, or changing the dosage-form architecture.
• The patent’s strongest commercial risk is to cetalkonium-containing ophthalmic oil-in-water emulsions with strongly positive droplet charge.

Frequently Asked Questions

Can a formulation infringe if it contains cetalkonium chloride below 0.0005%?

It would not literally satisfy the concentration limitation of claims 1 and 15. The risk of infringement under the doctrine of equivalents would depend on the technical and legal circumstances.

Does the patent cover a cetalkonium chloride solution?

Generally, no. The independent claims require an emulsion. A solution lacking dispersed emulsion droplets would not satisfy the claimed emulsion and zeta-potential limitations.

Does the patent cover a water-in-oil ophthalmic emulsion?

Claim 15 is directed to an ophthalmic oil-in-water emulsion. Claim 1 does not expressly require oil-in-water structure, but the formulation must still satisfy the emulsion, cationic-agent, zeta-potential, and stability limitations.

Can a competitor avoid claim 17 by using benzalkonium chloride?

Possibly, but the answer depends on the specific homologue distribution and chemical identity. A benzalkonium formulation could still fall within the C12-C16 genus if it satisfies the remaining limitations.

Is cetalkonium chloride itself patent-protected by U.S. Patent 9,132,071?

No. The patent does not claim cetalkonium chloride as a standalone chemical compound. It claims emulsions containing the compound within specified structural, concentration, charge, and stability parameters.

References

1. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/patents/laws/patent-term-calculator
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
3. U.S. Food and Drug Administration. (n.d.). Patent certifications and the 30-month stay under the Hatch-Waxman Amendments. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/patent-certifications-and-30-month-stay
4. U.S. Patent and Trademark Office. (2015). U.S. Patent No. 9,132,071. Patent Center. https://patentcenter.uspto.gov/

Drugs Protected by US Patent 9,132,071

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			Y

Foreign Priority and PCT Information for Patent: 9,132,071

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	06291236	Jul 28, 2006

International Family Members for US Patent 9,132,071

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