Details for Patent: 9,789,078

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Which drugs does patent 9,789,078 protect, and when does it expire?

Patent 9,789,078 protects PICATO and is included in one NDA.

This patent has two patent family members in two countries.

Summary for Patent: 9,789,078

Title:	Method of topically treating actinic keratosis with ingenol mebutate cycle therapy
Abstract:	The present invention relates to cyclic or repeated use of the ingenol mebutate for topical treatment of actinic keratosis lesions. Generally speaking, the present invention comprises a first ingenol mebutate treatment cycle and a second ingenol mebutate treatment cycle, wherein the first treatment cycle topically treats a treatment area with a topical gel formulated with ingenol mebutate at a selected dosage strength for a specified treatment regimen, and the second ingenol mebutate treatment cycle comprises topically re-treating the treatment area with the same topical ingenol mebutate gel for the same specified treatment regimen, if following the first treatment cycle, the treatment area failed to clear or failed to remain clear of AK lesions. The present invention further relates to spot or individual lesion therapy in the treatment area following the topical bi-cyclic therapy with ingenol mebutate.
Inventor(s):	Kirsten Norrelund
Assignee:	Leo Laboratories Ltd
Application Number:	US14/401,492
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

United States Patent 9,789,078: Ingenol Mebutate Repeat-Treatment Patent Analysis

U.S. Patent No. 9,789,078 covers repeat topical treatment of actinic keratosis with ingenol mebutate, particularly repeated treatment cycles separated by a treatment-free interval. Its broadest independent claim is a regimen claim. The narrower claims add the approved 0.015% concentration, face or scalp treatment, treatment areas of up to about 25 cm², an interval of at least eight weeks, three consecutive daily applications per cycle, complete lesion clearance, and clearance assessed 12 months after the first cycle.

The patent is materially different from a basic composition patent. Its commercial value depends on whether a competing product uses the claimed repeated-treatment protocol. The claims do not cover every topical ingenol mebutate product or every single treatment of actinic keratosis.

What does U.S. Patent 9,789,078 protect?

The patent protects a method of treating diagnosed actinic keratosis lesions by administering topical ingenol mebutate in more than one treatment cycle, with a period without treatment between cycles.

Claim element	Scope
Disease	Actinic keratosis
Patient	A subject diagnosed with actinic keratosis lesions
Route	Topical administration
Active ingredient	Ingenol mebutate
Treatment structure	More than one treatment cycle
Required separation	Each cycle must be separated by an interval without treatment
Preferred interval	At least eight weeks in dependent claims
Dosage form	Topical formulation
Concentration	0.015% by weight in claims 3 and 8-22
Anatomical site	Face or scalp in claims 3, 8, 19 and related claims
Treatment area	Up to about 25 cm² in claims 4, 9, 10, 13, 16, 20 and related claims
Treatment duration	Three consecutive daily applications per cycle in claims 27 and 28
Outcome	Complete clearance of lesions in several dependent claims
Follow-up endpoint	Complete clearance evaluated 12 months after initiation of the first cycle in claims 7 and 18-22

Claim 1 is the principal scope claim. It requires only:

1. A diagnosed actinic keratosis condition;
2. Topical ingenol mebutate;
3. More than one treatment cycle; and
4. An interval without treatment between cycles.

Claim 1 does not expressly require the 0.015% concentration, an eight-week interval, a face or scalp treatment area, or a three-day application schedule.

How should the independent claims be read?

Claim 1: broad repeat-cycle method claim

Claim 1 covers repeated administration, but it does not specify the length of each cycle or the duration of the treatment-free interval. A cycle could be defined by the treatment regimen used in the patent specification, but the claim text itself does not expressly impose the three-day schedule later recited in claim 27.

The phrase “more than one treatment cycle” requires at least two cycles. Claim 2 confirms that interpretation by specifying at least two treatment cycles.

The phrase “each treatment cycle separated by an interval without treatment” excludes continuous daily administration without a treatment-free period. It also creates a potential claim-construction issue: the claim requires an interval, but claim 1 does not prescribe a minimum length. A brief interruption may satisfy the literal wording of claim 1, while claims 5 and 11-13 impose the narrower eight-week interval.

Claim 23: narrower regimen claim

Claim 23 adds multiple cumulative limitations:

• Treatment of lesions on the face or scalp;
• Ingenol mebutate at 0.15% by weight as supplied in the claim text;
• A treatment area of up to about 25 cm²;
• More than one treatment cycle;
• A treatment-free interval between cycles; and
• Complete clearance of the lesions in the treatment area.

This claim is substantially narrower than claim 1. It is also internally inconsistent with the 0.015% concentration recited in claims 3 and 8-22 and with the FDA-approved Picato face/scalp strength, which was 0.015% ingenol mebutate [2].

The “0.15%” limitation in claim 23 should be treated as legally significant unless the issued patent, certificate of correction, prosecution history, or claim-construction record establishes that the text is an obvious drafting or transcription error. A tenfold concentration difference is not ordinarily immaterial. The supplied claim text may therefore contain an error, but the issued patent record controls.

Which dependent claims create the strongest commercial limitations?

The most commercially relevant dependent claims are claims 3, 5, 11, 23-26, 27 and 28.

Claims	Added limitation	Commercial effect
3, 8	0.015% formulation applied to face or scalp	Tracks the marketed face/scalp strength and site
4, 9, 10	Treatment area up to about 25 cm²	Limits the protected field size
5, 11-13	At least eight weeks between cycles	Creates a defined repeat-treatment interval
6, 14-17	Complete clearance	Adds an outcome limitation
7, 18-22	Complete clearance at 12 months	Adds a long-term clinical endpoint
23	Face/scalp, 0.15% as written, up to 25 cm², repeat cycles and complete clearance	Narrow but highly cumulative claim
24-26	Two cycles, eight-week separation and 12-month clearance	Defines a specific repeat-treatment protocol
27-28	Daily topical treatment for three consecutive days per cycle	Aligns the cycle with the standard Picato face/scalp regimen

Claims 24-26 are especially important because they describe a repeat regimen with two cycles separated by eight weeks and a 12-month clearance endpoint. Claims 27 and 28 add the three-consecutive-day treatment cycle.

What is the scope of the 0.015% ingenol mebutate claims?

The 0.015% claims are directed to the face or scalp and are tied to repeated treatment cycles. They do not claim the concentration alone. A product containing 0.015% ingenol mebutate would not necessarily infringe merely because it has the same strength. The method of use must also satisfy the relevant cycle, interval, anatomical-site and, where applicable, clearance limitations.

The FDA-approved Picato label described ingenol mebutate gel 0.015% for face and scalp treatment applied once daily for three consecutive days. The label described 0.05% for trunk or extremities applied once daily for two consecutive days [2]. The patent’s repeat-cycle claims target use beyond that single standard cycle.

What is the significance of the eight-week treatment-free interval?

The eight-week interval is a narrowing limitation, not a requirement of claim 1. It appears in claim 5 and is incorporated into claims 11-13 and 17-21.

A regimen with two cycles separated by eight weeks would fall within the narrower eight-week claims if the other limitations are met. A regimen separated by six weeks could still potentially implicate claim 1 because claim 1 requires an interval but does not specify eight weeks. It would not satisfy claims expressly requiring at least eight weeks.

The interval also creates a practical infringement-screening point. A generic or follow-on product could attempt to avoid the narrow claims by labeling a single cycle only, discouraging repeat treatment, or specifying a different treatment interval. That strategy would not necessarily avoid claim 1 if physicians or patients use the product in repeated cycles and the patent claim is enforced against the relevant method actor.

What does “complete clearance” add to the patent scope?

“Complete clearance” is an outcome limitation in claims 6, 14-17 and 22-26. These claims require that the treatment achieve complete clearance of the actinic keratosis lesions in the treatment area.

The limitation narrows the claims compared with claim 1, which does not require a stated clinical result. It also creates proof issues. A claimant would need evidence that the accused method was practiced and that the required result occurred. The 12-month claims add a more specific temporal requirement: complete clearance must be evaluated 12 months after initiation of the first cycle.

Outcome limitations can be commercially important but may be less predictable in litigation than dosage and regimen limitations. Clearance depends on patient population, lesion burden, assessment methodology and follow-up compliance. The patent specification and prosecution history would be relevant to whether “complete clearance” means clearance of every lesion in the defined treatment area or a clinical trial endpoint with a particular assessment method.

What are the main infringement scenarios?

Literal infringement risk

A competing topical ingenol mebutate product would present the clearest risk if its label or clinical-use instructions recommend:

• More than one treatment cycle;
• A treatment-free interval between cycles;
• Treatment of actinic keratosis;
• A face or scalp treatment area;
• A 0.015% formulation;
• An area of up to approximately 25 cm²; and
• Three daily applications per cycle.

A label that expressly recommends two cycles separated by eight weeks would map closely to claims 11, 12, 24 and 25.

Physician or patient-directed use

A single-cycle product label may reduce induced-infringement risk, but it does not eliminate all exposure. Repeated off-label use could still create method-of-use issues depending on who directs the use, the evidence of intent, and the governing infringement theory under 35 U.S.C. § 271(b) and (c) [5].

Design-around options

Potential design-around variables include:

• Using a different active ingredient;
• Avoiding ingenol mebutate;
• Limiting the label to one treatment cycle;
• Using a different concentration;
• Treating a different anatomical site;
• Using a treatment area outside the claimed size;
• Avoiding an eight-week interval; or
• Avoiding a label promise of complete clearance.

These options do not automatically avoid claim 1, which is broader as to concentration, site, area and interval. They are more relevant to the narrower dependent claims and claim 23.

When does U.S. Patent 9,789,078 lose exclusivity?

The patent issued on October 17, 2017. Its nominal term is generally 20 years from the applicable earliest nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and any patent-term extension [1, 5].

Public patent records associate the patent family with a 2012 priority period. On that basis, the nominal expiration is expected to fall in 2032, subject to the official USPTO term calculation. The exact enforceable expiration should be taken from the USPTO patent-term data rather than calculated solely from the issue date or a provisional priority date.

The patent does not receive biologic exclusivity. Ingenol mebutate is a small molecule, so biosimilar exclusivity concepts do not apply.

What was the FDA status of Picato and ingenol mebutate?

The FDA approved Picato gel for topical treatment of actinic keratosis in 2012. The product used ingenol mebutate at 0.015% for the face and scalp and 0.05% for the trunk and extremities [2].

In 2020, LEO Pharma announced worldwide discontinuation of Picato. The FDA issued a safety communication concerning an increased incidence of skin tumors in treated areas and advised patients to stop using Picato [3]. The European Medicines Agency recommended suspension of Picato marketing authorization in 2020 [4].

The commercial discontinuation materially reduces present product revenue exposure. It does not, by itself, cancel an issued patent. Patent enforceability, listing status and potential future use remain separate questions.

What is the Orange Book status of U.S. Patent 9,789,078?

The Orange Book is the relevant FDA database for patents submitted for approved small-molecule drug products [6]. A patent’s inclusion depends on the NDA holder’s submission and FDA’s listing determination. A patent can exist and remain enforceable without being listed in the Orange Book.

For this patent, the key issue is that the claims are method-of-use claims directed to repeat treatment of actinic keratosis. If listed against the Picato NDA, a generic applicant could potentially address it through a Paragraph IV certification, a section viii statement where the use is carved out, or a certification that the patent is not applicable, depending on the listing and proposed label.

The patent’s practical Orange Book significance has declined because Picato was discontinued. A Paragraph IV challenge would still be relevant if an applicant sought approval for an ingenol mebutate product or if the NDA remained commercially useful, but the absence of current marketing reduces the near-term incentive for such a filing.

Which companies are challenging the patent?

No specific Paragraph IV challenger or federal patent litigation can be established from the supplied claim text alone. A complete litigation conclusion requires the current USPTO, FDA Orange Book, PACER and docket records.

The relevant commercial parties are LEO Pharma A/S as the Picato sponsor and patent owner or associated rights holder, generic dermatology manufacturers, and any future applicant seeking approval for ingenol mebutate gel. Because Picato was withdrawn from commercial distribution, the competitive landscape is primarily a discontinued-product and freedom-to-operate question rather than an active branded-versus-generic launch contest.

How strong is the patent estate for repeat ingenol mebutate treatment?

The patent has moderate technical breadth but limited practical breadth.

Strength factor	Assessment
Claim type	Method-of-treatment claims
Broadest claim	More than one topical treatment cycle with an interval without treatment
Composition protection	None apparent from the supplied claims
Single-cycle use	Not covered by claim 1
Concentration flexibility	Broad in claim 1; narrowed to 0.015% in several dependents
Clinical outcome	Required only in selected dependent claims
Geographic scope	United States only
Biosimilar relevance	None
Generic substitution risk	Depends on label and actual repeat-treatment use
Commercial relevance	Reduced by Picato discontinuation
Design-around potential	Meaningful, particularly through labeling and regimen selection

The broadest risk is claim 1 because it does not require the eight-week interval, a particular concentration or complete clearance. The narrower claims may be easier to avoid but are closer to the historical Picato face/scalp regimen.

What patent landscape surrounds ingenol mebutate?

The patent landscape has at least four layers:

1. Composition and formulation patents covering ingenol mebutate gels or pharmaceutical compositions;
2. Manufacturing and purification patents covering production of ingenol mebutate;
3. Broad actinic keratosis treatment patents covering topical use;
4. Repeat-treatment and long-term clearance patents represented by U.S. Patent 9,789,078.

U.S. Patent 9,789,078 should therefore be analyzed as a regimen patent, not as the entire ingenol mebutate estate. Freedom-to-operate work must compare the proposed product, formulation, manufacturing process and label against the full family and any terminally disclaimed or continuation patents.

Key Takeaways

• U.S. Patent 9,789,078 principally protects repeated topical ingenol mebutate treatment cycles for actinic keratosis.
• Claim 1 is the broadest claim and requires more than one cycle separated by a treatment-free interval.
• The eight-week interval, 0.015% strength, face/scalp site, 25 cm² treatment area, three-day cycle and complete clearance are narrower limitations.
• Claim 23 states 0.15% as supplied, while several other claims state 0.015%. That tenfold difference must be resolved from the issued patent record.
• The patent does not claim ingenol mebutate composition alone and does not cover every single-cycle treatment.
• Ingenol mebutate is a small molecule, so biosimilar risk is not applicable.
• Picato was approved by FDA but discontinued after safety concerns concerning skin tumors.
• The expected patent term reaches into approximately 2032, subject to official patent-term adjustment and terminal-disclaimer data.
• Current commercial risk is limited by Picato’s discontinuation, but any future repeat-cycle ingenol mebutate product would require a claim-by-claim freedom-to-operate review.

FAQs

Does U.S. Patent 9,789,078 cover one three-day Picato treatment?

No. The supplied claims generally require more than one treatment cycle. A single three-day cycle alone would not satisfy the repeat-cycle limitation in claim 1.

Does changing the interval from eight weeks avoid the patent?

It may avoid claims expressly requiring at least eight weeks, but claim 1 does not state a minimum interval. A different interval must therefore be evaluated against the full wording of claim 1 and the patent’s prosecution history.

Does the patent cover ingenol mebutate 0.05% for the trunk or extremities?

The supplied claims do not expressly require the 0.05% strength or trunk/extremity treatment. Claim 1 is not limited to 0.015%, but the other claims focus mainly on 0.015% treatment of the face or scalp.

Can a generic applicant use a Paragraph IV certification against this patent?

Potentially, if the patent is listed in the Orange Book for the relevant NDA and the applicant seeks approval for a use covered by the listing. The appropriate certification depends on the listing and the proposed label.

Is U.S. Patent 9,789,078 still commercially important after Picato’s withdrawal?

Its immediate commercial value is reduced, but it remains relevant to any future U.S. development, licensing transaction or reintroduction involving repeated topical ingenol mebutate treatment.

References

1. Google Patents. (2017). US9789078B2: Treatment of actinic keratosis. U.S. Patent and Trademark Office patent records.
2. U.S. Food and Drug Administration. (2019). Picato (ingenol mebutate) gel prescribing information.
3. U.S. Food and Drug Administration. (2020). FDA warns of increased risk of death from skin cancer with Picato (ingenol mebutate) gel.
4. European Medicines Agency. (2020). EMA recommends suspension of Picato as a precaution.
5. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension resources.
6. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

Drugs Protected by US Patent 9,789,078

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Leo Labs	PICATO	ingenol mebutate	GEL;TOPICAL	202833-001	Jan 23, 2012		DISCN	Yes	No	9,789,078					TOPICAL TREATMENT OF ACTINIC KERATOSIS OF THE FACE OR SCALP USING MORE THAN ONE TREATMENT COURSE OF INGENOL MEBUTATE

Foreign Priority and PCT Information for Patent: 9,789,078

PCT Information
PCT Filed	May 15, 2013	PCT Application Number:	PCT/EP2013/060024
PCT Publication Date:	November 21, 2013	PCT Publication Number:	WO2013/171258

International Family Members for US Patent 9,789,078

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2849742
World Intellectual Property Organization (WIPO)	2013171258