US Patent 11,806,322: Mirdametinib Patent Scope, Claims, Expiration and Generic Risk
US Patent 11,806,322 protects treatment protocols using mirdametinib for patients aged two years and older with NF1-associated inoperable plexiform neurofibromas. Its core limitations are the disease population, oral administration, first-day exposure measured by AUC0-tau, body-surface-area dosing, intermittent treatment, dose reductions, and clinical response.
The patent is a method-of-use patent rather than a broad composition-of-matter patent. Its commercial relevance increased after FDA approval of Gomekli (mirdametinib) in February 2025 for adults and pediatric patients with NF1-associated symptomatic, inoperable plexiform neurofibromas [2,3].
What does US Patent 11,806,322 protect?
The patent protects administering mirdametinib to qualifying NF1 patients while achieving a specified first-day systemic exposure.
| Feature |
Scope under the claims |
| Active ingredient |
Mirdametinib |
| Route |
Oral administration |
| Disease |
Neurofibromatosis type 1-associated plexiform neurofibromas |
| Patient age |
Two years or older |
| Tumor status |
Inoperable; symptomatic, progressive or causing significant morbidity in dependent claims |
| Core pharmacokinetic limit |
First-day AUC0-tau below 300 ng·h/mL |
| Narrower exposure limits |
AUC0-tau below 200 ng·h/mL and below 100 ng·h/mL |
| Dose schedule |
Twice daily, with body-surface-area-based starting doses |
| Treatment cycle |
Three weeks on treatment followed by one week off |
| Maximum dose |
4 mg twice daily |
| Response |
At least 20% reduction in PN volume by volumetric MRI |
| Symptom outcomes |
Reduced pain intensity and pain interference |
| Adverse-event management |
Defined dose reductions, including for acneiform adverse events |
| Pediatric range |
Claims expressly cover patients aged two to 15 years |
The independent claims are claims 1, 3 and 24. Claim 1 is the principal disease-treatment claim. Claim 3 narrows the disease population to patients with progressive PN or PN causing significant morbidity. Claim 24 separately claims initial administration of 1 mg twice daily with the same AUC0-tau limitation.
How do the independent claims differ?
Claim 1: broadest principal treatment claim
Claim 1 covers treating a patient at least two years old who has NF1-associated inoperable PN by orally administering an effective amount of mirdametinib, provided that the first-day dose produces an AUC0-tau below 300 ng·h/mL.
The claim does not require:
- A symptomatic tumor;
- A progressive tumor;
- A particular body-surface area;
- A specific starting dose;
- A 21-days-on, seven-days-off cycle;
- A documented 20% tumor response; or
- A specific NF1 diagnostic test.
Those features appear in dependent claims or in the narrower independent claims.
Claim 3: progressive or high-morbidity disease
Claim 3 requires NF1-associated inoperable PN that is either progressing or causing significant morbidity. It retains the same oral mirdametinib and first-day AUC0-tau below 300 ng·h/mL requirements.
This claim tracks the clinical population used in the FDA-approved indication. FDA describes Gomekli as indicated for adults and pediatric patients two years and older with NF1-associated symptomatic, inoperable PN [2].
Claim 24: specific 1 mg twice-daily initiation
Claim 24 requires administration of 1 mg mirdametinib twice daily on the first treatment day and requires AUC0-tau below 300 ng·h/mL.
This claim is narrower than claim 1 because it fixes the initial dose. It is most relevant to smaller pediatric patients. The approved label uses body-surface-area-based dosing, with 1 mg twice daily assigned to patients below the lowest specified body-surface-area threshold [2].
What patient populations are covered?
Claims 2, 6 through 13 and 23 define multiple overlapping NF1-PN populations.
Clinical disease characteristics
The claims cover patients with:
- Symptomatic PN;
- Progressive PN;
- PN causing significant morbidity;
- Head and neck lesions compromising the airway or great vessels;
- Brachial or lumbar plexus lesions causing nerve compression or functional loss;
- Disfiguring or deforming lesions;
- Limb hypertrophy or loss of extremity function;
- Painful lesions; and
- Paraspinal lesions.
Claim 9 expands the disfigurement limitation to head and neck tumors and tumors elsewhere that cannot be concealed by standard clothing.
NF1 diagnostic criteria
Claims 11 through 13 use clinical and molecular criteria, including:
- Café-au-lait macules;
- Axillary or inguinal freckling;
- Optic glioma or optic pathway glioma;
- Lisch nodules or choroidal abnormalities;
- Distinctive osseous lesions;
- A first-degree relative with NF1; and
- A pathogenic NF1 variant documented in qualified laboratory testing.
These claims are important because they define who qualifies as an NF1 patient for purposes of the claimed treatment. Claim 12 requires a constitutional NF1 mutation documented by a Clinical Laboratory Improvement Amendments and College of American Pathologists-certified laboratory.
What dosing regimen is protected?
Claim 14 protects body-surface-area-based initial dosing:
| Body surface area |
Initial dose |
| No more than 0.69 m² |
1 mg twice daily |
| 0.70 to 1.04 m² |
2 mg twice daily |
| 1.05 to 1.49 m² |
3 mg twice daily |
| At least 1.50 m² |
4 mg twice daily |
Claim 15 sets 4 mg twice daily as the maximum dose. Claim 16 requires administration during the first three weeks of each four-week period, followed by a one-week interruption.
FDA’s approved dosing regimen is also based on body surface area and uses a 21-days-on, seven-days-off cycle [2]. The alignment between the patent claims and the approved label makes the dosing claims commercially important, although infringement would still require satisfaction of every claim element.
What does the AUC0-tau limitation mean?
AUC0-tau is the area under the plasma concentration-time curve over one dosing interval. In these claims, the relevant measurement is the exposure produced on the first day of treatment.
The principal thresholds are:
| Claim |
First-day AUC0-tau limitation |
| Claims 1 and 3 |
Less than 300 ng·h/mL |
| Claim 4 |
Less than 200 ng·h/mL |
| Claim 5 |
Less than 100 ng·h/mL |
| Claim 24 |
Less than 300 ng·h/mL after 1 mg twice daily |
This limitation creates a technical enforcement issue. A product label alone may not establish the patient's actual first-day AUC0-tau. Enforcement would likely require pharmacokinetic evidence, clinical-study data, prescribing or dosing records, or proof that the accused regimen necessarily produces the claimed exposure.
The AUC limitation also narrows the claims relative to a conventional method-of-treatment claim. A generic or competing product could attempt to avoid literal infringement by using a regimen that does not produce the specified first-day exposure, although other patent claims, regulatory requirements and inducement theories could remain relevant.
What treatment outcomes are protected?
Claim 17 requires at least a 20% reduction in PN volume measured by volumetric MRI. Claims 18 and 19 cover reduced pain intensity and reduced pain interference.
These are outcome-based dependent claims. They may be difficult to establish before treatment because a treatment provider cannot know in advance whether a patient will achieve the claimed response. They are more useful as evidence of practicing the treatment method than as the primary barrier to market entry.
Claim 25 adds a pre-treatment selection step. The provider must determine whether to select mirdametinib and select it at least partly based on objective response rate, defined as at least a 20% decrease in tumor size using centrally read MRI volumetric analysis. Claim 26 specifies a response rate of at least 70%.
The selection claims may raise divided-infringement and proof issues because the relevant steps may be performed by different actors, including physicians, treatment centers and patients.
How are adverse-event dose reductions protected?
Claims 20 through 22 protect dose modification after an adverse event, including acneiform dermatitis.
| Dose at time of event |
Reduced dose |
| 1 mg twice daily |
1 mg in the morning only |
| 2 mg twice daily |
2 mg in the morning and 1 mg in the afternoon or evening |
| 3 mg twice daily |
2 mg twice daily |
| 4 mg twice daily |
3 mg twice daily |
Claim 21 specifies acneiform adverse events. Claim 22 adds topical clindamycin treatment.
These claims cover management of treatment toxicity rather than the initial therapeutic use alone. Their practical value depends on whether the FDA-approved label, clinical protocols or standard practice direct providers toward the claimed modifications.
When does US Patent 11,806,322 expire?
US Patent 11,806,322 was granted on December 5, 2023. Public patent records identify a nominal patent-term endpoint in 2039, based on the relevant US application filing chronology [1].
| Event |
Date |
| Patent grant |
December 5, 2023 |
| Nominal term endpoint |
2039, subject to USPTO term calculation |
| FDA approval of Gomekli |
February 11, 2025 |
| Pediatric indication |
Included in FDA approval for patients two years and older |
The exact enforceable expiration date depends on the USPTO patent-term-adjustment calculation and any applicable patent-term extension. A method-of-use patent does not automatically receive the same regulatory extension treatment as every other patent associated with an approved drug. The Orange Book listing and FDA patent-term records control the commercial exclusivity analysis.
What is the Orange Book status of US Patent 11,806,322?
The patent is relevant to Gomekli because its claims substantially track the approved NF1-PN treatment population and dosing regimen. FDA Orange Book relevance depends on whether the patent has been submitted by the NDA holder and accepted for listing against the approved product.
An Orange Book listing can trigger a statutory 30-month stay if a generic applicant files a Paragraph IV certification and the patent owner or NDA holder brings infringement litigation within the applicable period under the Hatch-Waxman framework [4,5].
The patent’s status should be separated into three questions:
- Whether the patent is listed against the Gomekli NDA;
- Whether the listing covers the approved indication or dosing regimen; and
- Whether a generic applicant has submitted a Paragraph IV certification.
The patent claims alone do not establish that a Paragraph IV certification has been filed.
Which companies are challenging mirdametinib exclusivity?
No Paragraph IV challenger or US litigation event is established by the patent claims provided. The principal commercial parties are SpringWorks Therapeutics, the Gomekli sponsor, and Pfizer, which previously developed mirdametinib and licensed rights to SpringWorks [6].
The likely challenge routes are:
- An ANDA for a generic mirdametinib product;
- A section 505(b)(2) application using mirdametinib with a modified formulation, dosing regimen or indication;
- A non-infringement position based on the AUC0-tau limitation;
- An invalidity challenge directed to anticipation, obviousness, written description or enablement; and
- A regulatory strategy that omits the patented NF1-PN indication through a section viii statement, if legally and commercially viable.
Because Gomekli is a small-molecule drug, biosimilar litigation is not the relevant pathway. Generic and 505(b)(2) challenges are the principal US regulatory risks.
How strong is the patent estate for mirdametinib?
The estate has several layers, but US Patent 11,806,322 is principally an indication and regimen patent.
| Patent layer |
Strategic function |
Relevance of US 11,806,322 |
| Composition of matter |
Protects the active molecule |
Not the principal subject of these claims |
| Salt, crystal or solid form |
Protects physical drug forms |
Not apparent from the supplied claims |
| Formulation |
Protects dosage form or release profile |
Not claimed in the supplied claims |
| Method of treatment |
Protects use in NF1-PN |
Core function of the patent |
| Pharmacokinetic regimen |
Protects exposure target |
Central limitation |
| Pediatric dosing |
Protects age and body-surface-area dosing |
Claims 14, 23 and 24 |
| Toxicity management |
Protects dose reductions and supportive care |
Claims 20 through 22 |
| Diagnostic selection |
Protects patient-selection steps |
Claims 11 through 13 and 25 through 26 |
The strongest commercial claims are likely claims 1, 3, 14, 15, 16 and 24 because they track ordinary use of the approved product. Claims 4, 5, 17 through 22 and 25 through 26 are narrower and may present greater proof or enforcement challenges.
The central vulnerability is claim construction around “to provide an AUC0-tau less than 300 ng·h/mL.” The claim may be attacked as indefinite or insufficiently enabled if the patent does not provide a reliable method for determining the exposure threshold across patients, doses and clinical conditions. The patent owner would argue that pharmacokinetic measurement and the disclosed dosing regimens provide an objective boundary.
What generic launch scenarios exist?
Launch after patent expiration
A generic company can launch after all blocking patents and regulatory exclusivities expire, subject to FDA approval.
Paragraph IV launch
A generic applicant can file an ANDA with a Paragraph IV certification alleging that the listed patent is invalid, unenforceable or not infringed. Litigation could result in a 30-month stay, subject to statutory exceptions and court decisions [4,5].
Section viii carve-out
A generic applicant may seek approval for indications or dosing instructions outside the patented method, if the FDA-approved labeling can omit the protected use without encouraging infringement. This route may be difficult where the approved product’s primary commercial use is NF1-associated PN.
At-risk launch
A generic company could launch before final resolution of patent litigation. The principal exposure would include an injunction, damages and potentially enhanced damages if infringement is found.
What is the commercial exposure?
Gomekli was approved for a rare-disease population with no established generic substitute at the time of approval. The addressable market is concentrated in NF1 patients with symptomatic or progressive inoperable PN. The patent therefore has high strategic relevance even though it does not broadly cover every use of mirdametinib.
Revenue exposure depends on:
- The proportion of Gomekli sales generated by the NF1-PN indication;
- Whether the patent is Orange Book-listed;
- The presence of composition or formulation patents with earlier or later expiration dates;
- Any pediatric exclusivity;
- Generic labeling strategy;
- AUC-based infringement proof; and
- The commercial feasibility of a non-infringing 505(b)(2) product.
Key Takeaways
- US Patent 11,806,322 is a mirdametinib method-of-treatment patent for NF1-associated inoperable PN.
- The central limitation is first-day AUC0-tau below 300 ng·h/mL.
- Dependent claims cover lower exposure thresholds, pediatric dosing, body-surface-area dosing, intermittent administration, MRI response, pain reduction and adverse-event management.
- The claims closely track the FDA-approved Gomekli population and dosing framework.
- The patent is not a broad composition-of-matter claim based on the supplied claim set.
- AUC measurement creates both a technical limitation and a potential enforcement burden.
- Generic challenges would proceed through ANDA Paragraph IV, section viii or 505(b)(2) strategies, not biosimilar procedures.
- The nominal patent term extends into 2039, subject to the official USPTO term calculation and any applicable extension.
- Orange Book listing and Paragraph IV activity must be assessed from current FDA and court records, not inferred solely from the patent claims.
FAQs
Does US Patent 11,806,322 cover all mirdametinib uses?
No. The supplied claims are directed to treating patients with NF1-associated inoperable plexiform neurofibromas. They do not broadly claim every disease, formulation or use of mirdametinib.
Does the patent require a patient to have symptomatic plexiform neurofibromas?
Claim 1 does not expressly require symptomatic PN. Claims 2 and 3 add symptomatic, progressive or significant-morbidity limitations.
Can a generic avoid the patent by changing the tablet strength?
Not necessarily. Changing tablet strength may avoid a particular dosing limitation only if the resulting regimen does not satisfy every element of the asserted claim. Other method claims may still apply.
Is an AUC0-tau below 300 ng·h/mL required for every treatment cycle?
The claims expressly refer to the first day of treatment. They do not, on their face, require the same AUC threshold to be demonstrated during every later cycle.
Could a biosimilar challenge Gomekli?
No. Mirdametinib is a small-molecule drug. The relevant competitive pathways are an ANDA for a generic product or a 505(b)(2) application, not a biosimilar application.
References
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United States Patent and Trademark Office. (2023). U.S. Patent No. 11,806,322, methods of treating neurofibromatosis type 1-associated plexiform neurofibromas.
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U.S. Food and Drug Administration. (2025). Gomekli (mirdametinib) prescribing information.
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U.S. Food and Drug Administration. (2025, February 11). FDA approves mirdametinib for neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas.
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
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Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).
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SpringWorks Therapeutics, Inc. (2018). SpringWorks enters into global licensing agreement with Pfizer for mirdametinib.
