US Patent 9,233,117: Claim Scope, Orange Book Position, Litigation Risk and Generic Entry Analysis

US Patent 9,233,117 protects once-daily topical administration of 1% ivermectin cream for inflammatory lesions of rosacea. Its strongest protection is directed to the clinical-use profile of Soolantra, including early lesion-count reduction, relapse performance versus twice-daily 0.75% metronidazole, pharmacokinetic parameters, and the marketed cream’s excipient system. The patent was granted to Galderma and is listed in the FDA Orange Book for Soolantra. Its expected expiration date is April 15, 2031, subject to any applicable patent-term adjustment or regulatory extension shown in the official patent and Orange Book records. [1][2]

The patent is a method-of-treatment patent, not a composition claim covering every ivermectin cream. An ANDA applicant can therefore target it by challenging one or more administration, clinical-outcome, formulation, or pharmacokinetic limitations.

What patent is US 9,233,117 and what does it protect?

US 9,233,117 B2, titled around ivermectin treatment for rosacea, covers methods using a pharmaceutical composition containing 1% by weight ivermectin administered topically once daily to rosacea-affected skin. The patent issued January 12, 2016. [1]

Item	Details
Patent	US 9,233,117 B2
Patent type	Utility patent
Patent holder	Galderma-related entities
Active ingredient	Ivermectin
Dosage form	Topical cream or comparable topical pharmaceutical composition
Concentration	1% by weight ivermectin
Administration	Once daily
Disease	Inflammatory lesions of rosacea
Core clinical limitation	Significant reduction in inflammatory lesion count as early as two weeks
Grant date	January 12, 2016
Expected expiration	April 15, 2031, based on the published patent-family term information
Regulatory product	Soolantra ivermectin 1% cream
FDA application	NDA 206255
Exclusivity status	Original three-year FDA exclusivity expired in 2017

The claims track the clinical and pharmacokinetic data associated with Soolantra. They do not cover oral ivermectin, ivermectin used for unrelated parasitic diseases, or a topical product that lacks the claimed 1% concentration.

How broad are the independent claims?

Claims 1 and 10 are the two independent method claims.

Claim 1

Claim 1 requires all of the following:

A subject in need of treatment.
Inflammatory lesions of rosacea.
Topical administration to the affected skin area.
Once-daily administration.
A composition containing 1% by weight ivermectin.
A pharmaceutically acceptable carrier.
Significant reduction in inflammatory lesion count as early as two weeks after initial treatment.

Claim 1 is commercially important because it captures the central labeled use of Soolantra. It is broader than the dependent claims because it does not require a specific excipient list, exact pharmacokinetic value, relapse period, baseline lesion count, or moderate-to-severe disease classification.

The main infringement questions would concern the meaning and proof of the clinical limitations. A generic product could contain 1% ivermectin and be labeled for once-daily rosacea treatment, but the applicant could argue that the two-week reduction limitation is not met, is not inherent in every patient, or is not a limitation of the administered method. The strength of that argument would depend on claim construction, the proposed label, clinical data, and the patent’s specification.

Claim 10

Claim 10 repeats the once-daily 1% ivermectin treatment method but adds specific steady-state pharmacokinetic limitations:

Mean Cmax of 2.10 ± 1.04 ng/mL;
Cmax range of 0.69-4.02 ng/mL;
Mean AUC0-24 of 36.14 ± 15.56 ng·hr/mL;
AUC0-24 range of 13.69-75.16 ng·hr/mL;
Steady state reached as early as two weeks.

Claim 10 is narrower than claim 1 in subject-matter scope, but it may be difficult to avoid if a therapeutically equivalent 1% cream produces substantially similar systemic exposure. The claim also creates proof questions because pharmacokinetic values may vary by patient population, application amount, skin condition, dosing compliance, and study design.

What do the dependent claims add?

Claims	Added limitation	Commercial or litigation effect
2, 11	Greater lesion-count reduction than twice-daily 0.75% metronidazole	Directly ties the claim to comparative clinical performance
3, 12	Longer relapse-free time than twice-daily 0.75% metronidazole	Protects a comparative durability result
4, 13	Median time to first relapse of at least 110 days	Adds a measurable clinical endpoint
5, 14	Moderate-to-severe papulopustular rosacea	Narrows the patient population
6, 15	At least 15 inflammatory lesions before treatment	Creates a baseline-disease limitation
7	Cmax of 0.5-10 ng/mL and AUC0-24 of 10-100 ng·hr/mL at steady state	Broadens the PK range relative to claim 10
8, 16	Defined excipient classes and exclusions	Protects formulation architecture rather than only the active ingredient
9, 18	Mean terminal half-life of approximately 145 hours	Adds a long-exposure pharmacokinetic limitation
17	Specific Soolantra-like excipient formulation	Narrow product-specific formulation protection
19	Median inflammatory-lesion reduction of approximately 27% or more	Adds a quantitative efficacy threshold

Claims 8, 16 and 17 are particularly relevant to a generic cream that uses the same or substantially similar excipient system. Claim 17 identifies a formulation containing carbomer copolymer type B, cetyl alcohol, dimethicone, glycerin, isopropyl palmitate, oleyl alcohol, phenoxyethanol, propylene glycol, sorbitan monostearate, stearyl alcohol, water and other listed ingredients.

What formulations are protected by US 9,233,117?

The formulation claims use a Markush structure. They cover combinations selected from several ingredient groups rather than one mandatory recipe.

Oily phase

The claims identify ingredients such as:

Dimethicone;
Cyclomethicone;
Isopropyl palmitate;
Isopropyl myristate;
Cetyl alcohol;
Cetostearyl alcohol;
Stearyl alcohol;
Palmitostearic acid;
Stearic acid;
Self-emulsifiable wax.

Surfactants and emulsifiers

The protected alternatives include:

Glyceryl/PEG 100 stearate;
Sorbitan monostearate;
Sorbitan palmitate;
Steareth-2;
Steareth-20;
Steareth-21;
Ceteareth-20.

Solvents and penetration agents

The claims list:

Propylene glycol;
Oleyl alcohol;
Phenoxyethanol;
Glyceryl triacetate.

Gelling agents

The covered categories include carbomers, cellulose gelling agents, xanthan gums, aluminum magnesium silicates, guar gums, polyacrylamides and modified starches. The claims expressly exclude a particular aluminum magnesium silicate/titanium dioxide/silica combination.

The formulation protection is narrower than a pure 1% ivermectin composition claim. A generic manufacturer can reduce risk by using a materially different vehicle, but it must still address the independent once-daily method claims if its label directs treatment of rosacea with 1% ivermectin.

When does US 9,233,117 lose exclusivity?

The expected patent expiration date is April 15, 2031. The expiration calculation follows the patent-family filing history reflected in the USPTO record. [1]

Exclusivity layer	Date or status
FDA approval of Soolantra	December 2014
Three-year FDA exclusivity	Expired December 2017
US 9,233,117 grant	January 12, 2016
Expected patent expiration	April 15, 2031
Potential generic pathway	ANDA with Paragraph IV or post-expiration approval

The three-year regulatory exclusivity did not block ANDA filing indefinitely. The principal commercial barrier is the patent estate and any related patents listed for Soolantra, not the original FDA exclusivity period.

What is the Orange Book status of Soolantra and US 9,233,117?

Soolantra is FDA-approved under NDA 206255 for the topical treatment of inflammatory lesions of rosacea. The FDA-approved product is ivermectin 1% cream administered once daily. [2]

US 9,233,117 is listed in the Orange Book in connection with Soolantra’s approved use. Orange Book listing gives the patent holder a statutory basis to receive notice of an ANDA Paragraph IV certification and to file an infringement action under the Hatch-Waxman framework. [2][3]

The listing does not itself establish that every claim is valid or infringed. It creates a regulatory and litigation mechanism. An ANDA applicant may certify that the patent is invalid, unenforceable or will not be infringed. A timely infringement action can trigger a 30-month stay of FDA approval, subject to statutory exceptions and court developments. [3]

Which companies are challenging the Soolantra patent estate?

Public generic activity has focused on ivermectin 1% cream manufacturers seeking ANDA approval. The relevant risk group includes large generic manufacturers and dermatology-focused companies that can formulate a topical cream and rely on the Soolantra safety and efficacy framework.

Known competitive activity should be assessed patent-by-patent and case-by-case because:

An ANDA may contain a Paragraph IV certification against US 9,233,117.
A generic may use a section viii statement and omit a patented indication where FDA labeling permits.
A manufacturer may settle litigation before commercial launch.
A product may receive approval but remain subject to a launch restriction under a settlement agreement.
Patent challenges may target only the listed method patent and not unlisted formulation or manufacturing rights.

The claim set supplied does not identify a specific ANDA filer, Paragraph IV notice, district-court case number or settlement agreement. Those matters cannot be attributed to a particular company solely from the patent claims.

What Paragraph IV challenges are available?

A generic applicant could attack US 9,233,117 on several grounds.

Noninfringement

A challenger could argue that its label does not require:

Once-daily administration;
Treatment of inflammatory lesions of rosacea;
The claimed two-week clinical response;
The specified Soolantra-like excipients;
The claimed pharmacokinetic profile.

The most practical noninfringement route would be a label or formulation strategy that avoids one or more dependent claims. Avoiding dependent claims does not eliminate exposure under claim 1 if the approved use still instructs once-daily 1% ivermectin treatment for rosacea.

Invalidity

Potential validity theories include:

Anticipation based on earlier ivermectin rosacea treatment disclosures;
Obviousness based on known ivermectin topical formulations and rosacea treatment studies;
Lack of written description for the full Markush excipient groups;
Lack of enablement for the claimed clinical and PK outcomes across the full scope;
Indefiniteness involving terms such as “significant reduction,” “as early as 2 weeks,” “about,” and comparative relapse performance.

The clinical-result limitations can strengthen the patent against a purely structural obviousness attack if the record shows unexpected efficacy or durability. They can also create validity and infringement disputes because the endpoints depend on clinical-study design.

How strong is the patent estate?

US 9,233,117 has moderate-to-strong commercial relevance but uneven claim strength.

Factor	Assessment
Core product relevance	High; the claims track 1% once-daily ivermectin rosacea treatment
Orange Book leverage	High if listed against the approved indication
Composition protection	Limited; no broad standalone composition claim in the supplied claims
Formulation protection	Moderate; claims 8, 16 and 17 narrow the covered vehicles
Method-of-use protection	Strong commercial alignment with the Soolantra label
PK protection	Moderate; exact values may vary by patient and study
Design-around potential	Meaningful through formulation, labeling or dosing differences
Litigation leverage	High before expiration because an ANDA launch can trigger Hatch-Waxman litigation
Biosimilar relevance	None; ivermectin is a small molecule, not a biologic

The core vulnerability is that the patent claims a method with clinical and pharmacokinetic results rather than a broad chemical composition. A generic applicant may have credible arguments around inherency, claim construction and whether the claimed results are mandatory method steps. Galderma’s strongest position is likely against a product whose label closely mirrors Soolantra and whose formulation and exposure profile match the claimed data.

What generic launch scenarios exist?

Launch after patent expiration

A generic can obtain approval and launch after April 15, 2031, assuming no separate blocking patent, pediatric extension, injunction or settlement restriction applies.

Paragraph IV launch before expiration

An ANDA applicant may certify that US 9,233,117 is invalid, unenforceable or not infringed. Galderma can file suit within the statutory period, potentially delaying approval through the 30-month stay. A successful challenge could permit earlier launch.

Section viii carve-out

A generic could seek approval for a non-infringing use while omitting the patented rosacea indication. This strategy is difficult if rosacea is the principal or only commercially relevant use of the product and the proposed label still encourages the patented administration method.

At-risk launch

A company could launch after approval while litigation remains unresolved. This exposes the manufacturer to damages, a possible injunction and potential treble damages if willful infringement is established. The commercial value of an at-risk launch depends on market size, expected price erosion and the probability of patent invalidity.

How does Soolantra compare with metronidazole?

The patent expressly uses twice-daily 0.75% metronidazole as the comparator.

Attribute	Soolantra	Comparator in US 9,233,117
Active ingredient	Ivermectin	Metronidazole
Concentration	1%	0.75%
Administration	Once daily	Twice daily
Indication	Inflammatory lesions of rosacea	Rosacea
Claimed benefit	Greater lesion reduction	Reference treatment
Claimed durability	Longer relapse-free time	Reference treatment
Patent relevance	Protected method	Comparator limitation

These comparison claims increase commercial relevance because they link the patent to a differentiated dosing and efficacy proposition. They do not create a patent on metronidazole itself.

What manufacturing and geographic barriers remain?

The patent is limited territorially to the United States. Corresponding foreign-family rights must be analyzed separately by jurisdiction, including European, Canadian, Japanese and other national-phase records. A US design-around does not resolve foreign patent exposure.

Manufacturing barriers are lower than for biologics because ivermectin is a defined small molecule and the product is a conventional topical cream. The principal IP risks are:

Vehicle composition;
Emulsion stability;
Particle size and active dispersion;
Preservative system;
Manufacturing process parameters;
Regulatory bioequivalence and product-quality requirements;
Label-based method-of-use infringement.

FDA approval of a generic topical cream also requires sufficient product-quality and bioequivalence support. Patent clearance and regulatory approval are separate issues. [2][3]

What is the revenue exposure from US 9,233,117?

The patent’s revenue exposure is tied to the US Soolantra market and the price erosion that would follow generic entry. Because the claims cover the labeled once-daily rosacea use, an early successful Paragraph IV challenge could affect substantially all commercially relevant US ivermectin 1% rosacea sales.

The supplied patent record does not establish Soolantra’s current annual sales, net price, market share or the number of approved generic competitors. Revenue forecasting should therefore model:

Pre-expiration branded sales;
The probability and timing of ANDA approval;
Litigation duration;
Settlement launch dates;
Number of generic entrants;
Wholesale acquisition cost erosion;
Patient switching;
Reimbursement coverage;
Separate patents or regulatory exclusivities.

Key Takeaways

US 9,233,117 protects once-daily topical use of 1% ivermectin for inflammatory rosacea lesions.
Claims 1 and 10 are the commercial core.
Claims 8, 16 and 17 add formulation protection, with claim 17 closely tracking the Soolantra vehicle.
Claims 2, 3, 11 and 12 protect comparative outcomes versus twice-daily 0.75% metronidazole.
Claims 7, 9 and 10 protect specified systemic exposure and half-life characteristics.
The expected US patent expiration date is April 15, 2031.
FDA exclusivity for Soolantra expired in 2017; patent protection remains the principal barrier.
Ivermectin is a small molecule, so biosimilar risk is not applicable. Generic ANDA litigation is the relevant pathway.
The principal generic strategies are Paragraph IV invalidity or noninfringement, formulation design-around, section viii labeling and post-expiration launch.
The patent has high label relevance but does not provide broad standalone composition protection based on the claims supplied.

FAQs

Can a generic sell ivermectin 1% cream without infringing US 9,233,117?

Possibly, but a generic labeled for once-daily treatment of inflammatory rosacea would face substantial exposure under claim 1. A different formulation alone may not avoid the independent method claim.

Does US 9,233,117 cover oral ivermectin?

No. The supplied claims require topical administration to a skin area affected by inflammatory lesions of rosacea.

Does the patent cover ivermectin concentrations below 1%?

The independent claims require a composition comprising 1% by weight ivermectin. The supplied claims do not broadly cover all lower-concentration ivermectin products.

Can a generic avoid the metronidazole comparison claims?

Yes, the comparative claims are dependent claims. Avoiding those limitations would not by itself avoid claim 1 or claim 10.

Is Soolantra protected by a biosimilar pathway?

No. Soolantra contains ivermectin, a small-molecule active ingredient. A competing product would generally proceed through the ANDA framework rather than the biosimilar pathway.

References

United States Patent and Trademark Office. (2016). US Patent No. 9,233,117 B2: Ivermectin for treating rosacea.
U.S. Food and Drug Administration. (n.d.). Soolantra (ivermectin) cream, 1%: Prescribing information and approval records for NDA 206255.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Galderma Labs Lp	SOOLANTRA	ivermectin	CREAM;TOPICAL	206255-001	Dec 19, 2014	AB	RX	Yes	Yes	9,233,117	⤷ Start Trial				TREATMENT OF INFLAMMATORY LESIONS OF ROSACEA	⤷ 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
Australia	2014287408	⤷ Start Trial
Australia	2014287422	⤷ Start Trial
Brazil	112016000335	⤷ Start Trial
Brazil	112016000350	⤷ Start Trial
Canada	2916668	⤷ Start Trial
Canada	2916704	⤷ Start Trial
Chile	2016000008	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,233,117

Which drugs does patent 9,233,117 protect, and when does it expire?

Summary for Patent: 9,233,117