US Patent 10,617,693: Tirbanibulin Patent Scope, Claim Analysis, and Actinic Keratosis Landscape

US Patent 10,617,693 covers dose- and schedule-specific methods of treating actinic keratosis with tirbanibulin, the active ingredient in Klisyri. The patent is primarily a method-of-use patent, not a broad composition patent. Its commercial relevance is strongest because the FDA-approved Klisyri regimen falls within the patent's claimed topical treatment parameters. The patent's listed expiration is July 8, 2036, subject to any applicable patent-term adjustment or regulatory changes reflected in the current USPTO and FDA records. [1,2]

What drug and treatment does US Patent 10,617,693 cover?

The compound depicted in the patent claims is tirbanibulin, also known as KX2-391. Tirbanibulin is a topical microtubule inhibitor approved for the treatment of actinic keratosis on the face or scalp.

The patent covers administering tirbanibulin at a surface-area dose of approximately 0.02 mg/cm² to 0.1 mg/cm². It also claims absolute dose ranges, treatment-area sizes, dosing frequency, treatment duration, intermittent schedules, topical administration, and reduction of local skin reactions.

The relevant FDA-approved product is Klisyri 1% ointment, supplied in single-use 250 mg packets. A 1% formulation contains approximately 2.5 mg of tirbanibulin per packet. The labeled regimen is application once daily for five consecutive days to a contiguous treatment area of up to 25 cm². [2,3]

Product	Active ingredient	Strength	FDA indication	Labeled regimen
Klisyri	Tirbanibulin	1% ointment	Actinic keratosis of the face or scalp	Once daily for 5 days
Klisyri packet	Tirbanibulin	2.5 mg per 250 mg packet	Topical treatment	Apply entire packet to up to 25 cm²

The labeled dose is approximately 0.1 mg/cm² when 2.5 mg is applied over 25 cm². That dose is at the upper boundary of claim 1 and is also consistent with the absolute-dose range in claim 2.

What does claim 1 of US Patent 10,617,693 require?

Claim 1 is the only independent claim in the supplied claim set. It requires four principal elements:

A method of treating actinic keratosis.
A subject in need of treatment.
Administration of a therapeutically effective amount of the claimed compound.
Administration at approximately 0.02 mg/cm² to 0.1 mg/cm².

The claim does not expressly require topical administration, a particular formulation, a specific treatment area, or a particular dosing frequency. Those limitations are introduced by dependent claims.

Because claim 1 is a method claim, infringement generally turns on performance of the claimed treatment method. A product supplier would face greater risk if its FDA-approved labeling, promotional materials, instructions, or standard use directly encouraged administration of tirbanibulin within the claimed range.

The dose limitation is central. A treatment using the same active ingredient for actinic keratosis may fall outside literal infringement if it is administered below 0.02 mg/cm² or above 0.1 mg/cm². The term "about" expands the practical boundary, but its application depends on claim construction, intrinsic evidence, prosecution history, and the technical meaning of dosing variability in the field.

How do claims 2 through 8 define dose and treatment area?

Claims 2 through 8 connect the surface-area dose to an absolute amount and affected-area size.

Claims	Limitation	Commercial significance
2	Approximately 0.2 mg to 5 mg per affected area	Covers the approximate total dose used by a single Klisyri packet
3	Specific doses from 0.2 mg through 5 mg	Creates narrower literal-dose positions
4	Approximately 0.025 mg/cm² to 0.1 mg/cm²	Narrows the lower dose boundary
5	Specific surface-area doses from 0.02 mg/cm² through 0.1 mg/cm²	Provides enumerated dose positions
6	Affected area of approximately 1 cm² to 200 cm²	Broad area limitation
7	Specific areas from 25 cm² to 100 cm²	Includes the FDA-labeled 25 cm² area
8	Affected area is skin	Confirms the dermatologic application

The claims must be read cumulatively. For example, claim 6 depends on claim 2. A method covered by claim 6 must therefore include both the 0.2 mg to 5 mg total dose and the 1 cm² to 200 cm² treatment area.

The claimed ranges do not create unlimited coverage across every possible combination. A dose of 0.2 mg over 200 cm² would not satisfy the 0.02 mg/cm² lower density in claim 1. Conversely, 5 mg applied over 1 cm² would exceed the claimed density range in claim 1. Dependent-claim infringement requires that the dose, area, and resulting dose density be reconciled.

The FDA-approved regimen aligns particularly well with the following claimed parameters:

Approximately 2.5 mg total dose.
Approximately 25 cm² treatment area.
Approximately 0.1 mg/cm² dose density.
Topical administration to skin.
Once-daily administration.
Five-day treatment course.

What dosing schedules are protected by claims 9 through 18?

Claims 9 through 18 create a broad schedule network.

They include:

Once weekly.
Every two, three, four, five, six, or seven days.
Once, twice, three times, or four times daily.
Treatment for one through 21 days.
Treatment for one through five days.
Administration on one through six days per week.
Once- or twice-daily treatment followed by interruption.
Two, three, or four consecutive treatment days followed by a rest interval.
Treatment until the actinic keratosis is fully treated.

Claims 13 through 17 are particularly important because they cover intermittent regimens that may be developed to reduce local skin reactions. These claims can reach schedules that differ from the FDA-approved five-consecutive-day regimen.

The schedule claims are not independent of claim 1. Each requires the tirbanibulin dose density and actinic-keratosis treatment limitations of claim 1. A different schedule using a different concentration or dose may not infringe.

What do claims 19 through 25 protect?

Claims 19 through 25 narrow the patent toward practical dermatologic use.

Claim	Subject matter
19	Topical administration
20	Reduction in number or severity of local skin reactions or other adverse effects compared with other treatments
21	Once-daily administration
22	Three-day treatment
23	Five-day treatment
24	Approximately 0.02 mg/cm² once daily for three days
25	Approximately 0.02 mg/cm² once daily for five days

Claims 21 and 23 most closely track the frequency and duration of the Klisyri label. Claim 25 covers a lower-dose five-day regimen than the labeled 1% product regimen.

Claim 20 has a different character from the dose and schedule claims. It requires a comparative clinical outcome involving local skin reactions or other adverse effects. The claim may be harder to establish in litigation because the comparison treatment, patient population, endpoint, and causation must be defined through the patent's specification and prosecution record.

Claims 24 and 25 are narrow but commercially relevant. They may protect lower-dose regimens designed to preserve efficacy while improving tolerability. Their scope depends on how "about 0.02 mg/cm²" is construed and whether the accused regimen uses a materially different dose.

Does the FDA-approved Klisyri regimen fall within US Patent 10,617,693?

Yes. The approved regimen is substantially aligned with multiple claims.

Klisyri label element	Corresponding patent limitation
Tirbanibulin	Compound specified in claim 1
Treatment of actinic keratosis	Claim 1
Topical ointment	Claim 19
Once daily	Claims 9 and 21
Five days	Claims 10, 11, 22, and 23
Up to 25 cm²	Claims 6 and 7
Approximately 2.5 mg per packet	Claim 2
Approximately 0.1 mg/cm² over 25 cm²	Claims 1, 4, and 5

The strongest overlap is with claims 1, 2, 6, 7, 8, 9, 10, 19, 21, and 23. Claims 24 and 25 concern approximately 0.02 mg/cm², which is materially lower than the approximately 0.1 mg/cm² dose density produced by applying a 2.5 mg packet over 25 cm².

When does US Patent 10,617,693 expire?

The patent is associated with a July 8, 2036 expiration date in public patent and product-patent records. [1,4]

Event	Date
Earliest claimed priority date	July 8, 2015
US patent grant	April 14, 2020
Listed patent expiration	July 8, 2036
FDA approval of Klisyri	December 14, 2020
Five-year new chemical entity exclusivity	December 14, 2025

Patent expiration and FDA regulatory exclusivity are separate rights. The five-year new chemical entity exclusivity associated with FDA approval would not extend beyond the patent term, and the patent term extends well beyond the end of that regulatory exclusivity period. [2,5]

A current freedom-to-operate opinion should use the live USPTO patent record, the current Orange Book, terminal-disclaimer data, and any patent-term-adjustment entry. The practical commercial barrier is the later of the enforceable patent rights and any applicable FDA approval restrictions.

What is the Orange Book status of Klisyri?

Klisyri was approved under NDA 213189. FDA product-patent listings identify US Patent 10,617,693 as a patent relevant to the product's approved use. [2,4]

Regulatory item	Status
Product	Klisyri
Active ingredient	Tirbanibulin
Applicant/holder	Almirall, LLC
NDA	213189
Dosage form	Ointment
Strength	1%
Patent type	Method-of-use
Orange Book relevance	Patent listed against the approved actinic-keratosis use
Regulatory exclusivity	Five-year NCE exclusivity associated with 2020 approval

The Orange Book listing is important because an ANDA applicant must address listed patents through a Paragraph I, II, III, or IV certification. A Paragraph IV certification alleges that a listed patent is invalid, unenforceable, or not infringed.

Have generic manufacturers filed Paragraph IV challenges?

No publicly verified Paragraph IV litigation against US Patent 10,617,693 is identified in the supplied record. The absence of a confirmed challenge in that record does not establish that no confidential ANDA certification, notice letter, or later-filed action exists.

A generic applicant seeking approval before patent expiry could pursue several strategies:

Paragraph IV challenge to validity, enforceability, or infringement.
Paragraph III certification accepting delay until patent expiration.
Section viii statement carving out a patented method of use, if the remaining labeling supports approval.
A formulation or dosing strategy outside the patent's literal scope.

Because the patent claims the actinic-keratosis treatment method itself, a section viii strategy may be difficult if the proposed generic labeling necessarily includes the approved use of tirbanibulin for actinic keratosis.

A timely Paragraph IV notice followed by a patent lawsuit could trigger a statutory 30-month stay of FDA approval under the Hatch-Waxman framework, subject to statutory exceptions and court developments. [6]

What other patents protect tirbanibulin and Klisyri?

The tirbanibulin estate should be divided into four categories:

Active-ingredient and pharmacology patents

Earlier patents and patent families may cover tirbanibulin, related compounds, kinase or microtubule activity, and therapeutic use. These rights are distinct from US Patent 10,617,693 and may have earlier expiration dates.

Actinic-keratosis method patents

US Patent 10,617,693 is the principal identified patent for the disclosed dose and schedule combinations. It is more directly aligned with the commercial use than a broad discovery patent because it recites treatment of actinic keratosis at specified topical doses.

Formulation patents

Separate patents may cover ointment composition, excipients, particle size, stability, packaging, or delivery characteristics. A formulation patent can create a separate infringement risk even if a competitor avoids the claimed dosing schedule.

The 1% ointment and single-use packet are commercially important formulation and packaging features. A competitor could attempt to use a different vehicle, concentration, packet size, or dispensing format, but that design would still need to avoid both composition and method claims.

Manufacturing and process patents

Manufacturing rights may cover synthesis of tirbanibulin, intermediates, impurity control, crystallinity, scale-up, or preparation of the topical formulation. These rights can restrict supply even where a finished product design avoids the principal method-of-use patent.

How strong is the patent estate for Klisyri?

The estate has meaningful commercial strength because the patent's claimed regimen overlaps the FDA-approved product.

Strength factor	Assessment
Product-use overlap	High
Claim type	Method of treatment
Dose specificity	High
Schedule coverage	Broad
Formulation protection in the supplied claims	Limited
Dependence on clinical-use evidence	Moderate
Design-around potential	Moderate
Expiration relative to 2020 approval	Long remaining term
Generic substitution risk before 2036	Dependent on Orange Book scope and litigation

The principal weakness is claim specificity. A competitor may attempt to change the dose density, treatment area, treatment duration, frequency, formulation, or labeling. The principal strength is the large combination of overlapping claims, which makes a simple one-variable design-around less certain.

The patent does not claim every use of tirbanibulin. It does not, based on the supplied claims, broadly claim:

All pharmaceutical compositions containing tirbanibulin.
All topical formulations.
All treatments of skin disease.
All doses of tirbanibulin.
All methods of manufacturing tirbanibulin.
All actinic-keratosis treatments regardless of dose and schedule.

What generic launch scenarios exist for Klisyri?

Launch after patent expiry

A generic applicant may seek approval with a Paragraph III certification and launch after the listed patent expires. This is the lowest litigation-risk path but delays entry until 2036 unless the patent is earlier invalidated or removed.

Paragraph IV launch

A challenger could allege that the patent is invalid, unenforceable, or not infringed. Potential arguments could target written description, enablement, obviousness, indefiniteness of "about," anticipation, or the relationship between dose density and total dose.

Section viii carve-out

A narrow labeling carve-out could be considered if the proposed label excludes the patented use. This route is difficult where the entire approved indication is the patented actinic-keratosis method.

Dose or schedule design-around

A competitor could investigate a regimen outside the claimed ranges. That strategy carries risk because claims use "about," multiple dependent claims cover broad schedules, and the doctrine of equivalents may become relevant.

Alternative formulation

A different topical vehicle or delivery format may avoid formulation claims but would not necessarily avoid the method claims. If the alternative product is still used to treat actinic keratosis with tirbanibulin within the claimed dose range, method-of-use exposure could remain.

What licensing and commercial relationships affect Klisyri?

Tirbanibulin was developed by Athenex and commercialized in the United States by Almirall. Almirall obtained US rights to the product and markets Klisyri for actinic keratosis. [3,7]

The commercial relationship matters because patent enforcement, Orange Book listing, FDA supplements, and settlement decisions may be controlled by the NDA holder or its authorized patent owner. Publicly available product materials identify Almirall as the US commercial sponsor. The supplied record does not establish a public patent settlement with a generic challenger involving US Patent 10,617,693.

Key Takeaways

US Patent 10,617,693 is a tirbanibulin method-of-use patent for actinic keratosis.
Claim 1 covers approximately 0.02 mg/cm² to 0.1 mg/cm².
The FDA-approved Klisyri regimen falls within the patent's principal dose, area, frequency, topical-use, and five-day treatment claims.
The patent covers more than the approved regimen because it includes intermittent schedules, one- to 21-day courses, and multiple dose ranges.
Claims 24 and 25 target lower-dose regimens of approximately 0.02 mg/cm².
The listed patent expiration is July 8, 2036.
Klisyri received FDA approval on December 14, 2020, with five-year NCE exclusivity separate from the patent term.
The supplied record does not identify a confirmed Paragraph IV challenge or settlement involving this patent.
Generic entry could occur through patent litigation, a successful design-around, a labeling carve-out, or post-expiration approval.
The main commercial risk is method-of-use infringement, while separate risks may arise from formulation, manufacturing, and earlier tirbanibulin patents.

FAQs About US Patent 10,617,693

Is US Patent 10,617,693 a composition patent?

No. The supplied claims are method-of-treatment claims. They require treating actinic keratosis with the specified compound at claimed dose ranges and schedules.

Does Klisyri infringe claim 1?

The labeled Klisyri regimen appears to fall within claim 1 because it uses tirbanibulin to treat actinic keratosis at approximately 0.1 mg/cm². A legal infringement determination would depend on claim construction and the accused conduct.

Does the patent cover tirbanibulin use outside actinic keratosis?

Not under the supplied claims. Claim 1 requires treatment of actinic keratosis.

Can a generic use a different concentration and avoid the patent?

Possibly, but concentration alone is not determinative. The relevant questions include dose per unit area, total dose, treatment area, schedule, labeling, and whether the alternative falls within the claims or their equivalents.

What is the main patent risk for a tirbanibulin generic?

The main risk is that an ANDA label for actinic keratosis would encourage a regimen within the claimed dose and schedule ranges, creating a potential Paragraph IV dispute over US Patent 10,617,693.

References

United States Patent and Trademark Office. (2020). US Patent No. 10,617,693, Methods of treating actinic keratosis.
U.S. Food and Drug Administration. (2020). Klisyri (tirbanibulin) ointment, 1%: Prescribing information.
Almirall, LLC. (2020). Klisyri product information and prescribing materials.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Food and Drug Administration. (2020). FDA approves treatment for actinic keratosis.
United States Code. (2024). 21 U.S.C. § 355(j): Abbreviated applications for new drugs.
Athenex, Inc. (2020). Corporate and product disclosures concerning tirbanibulin and US commercialization rights.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Almirall	KLISYRI	tirbanibulin	OINTMENT;TOPICAL	213189-001	Dec 14, 2020		RX	Yes	Yes	10,617,693	⤷ Start Trial				TOPICAL TREATMENT OF ACTINIC KERATOSIS OF THE FACE OR SCALP	⤷ 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	2018231144	⤷ Start Trial
Australia	2024201828	⤷ Start Trial
Brazil	112019018687	⤷ Start Trial
Canada	3055938	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,617,693

Which drugs does patent 10,617,693 protect, and when does it expire?

Summary for Patent: 10,617,693