US Patent 11,969,414: Ripretinib and Itraconazole Patent Scope, Validity, and Market Impact

US Patent 11,969,414 covers a narrow clinical-management method for patients with advanced gastrointestinal stromal tumors who receive the approved 150 mg daily dose of ripretinib while taking itraconazole. The claim is directed to recognizing the approximately 99% increase in ripretinib exposure caused by itraconazole and monitoring the patient for ripretinib-related adverse events.

The patent does not broadly cover ripretinib, QINLOCK, treatment of gastrointestinal stromal tumors, or all CYP3A inhibitor combinations. Its practical scope depends on whether the accused treatment includes all of the following: advanced GIST, concurrent itraconazole, oral ripretinib at 150 mg daily, the claimed AUC increase, and monitoring for an adverse event.

What does US Patent 11,969,414 claim?

The supplied independent claim requires a method with five principal elements:

Claim element	Required limitation
Disease	Advanced gastrointestinal stromal tumor
Concomitant drug	Itraconazole administered concurrently
Ripretinib dose	150 mg orally once daily
Pharmacokinetic result	Ripretinib AUC0-inf increases by 99% compared with ripretinib alone
Clinical action	Monitoring the patient for an adverse event caused by the combination

The claim is a method-of-treatment claim rather than a composition, formulation, compound, manufacturing, or dosing-regimen claim in the conventional sense. It requires performance of the claimed clinical steps.

The claim is narrower than a claim covering:

ripretinib for GIST generally;
ripretinib with any CYP3A inhibitor;
ripretinib with itraconazole at any dose;
a reduced ripretinib dose during itraconazole treatment;
a pharmacokinetic interaction between ripretinib and itraconazole without patient monitoring; or
monitoring for toxicity in patients receiving ripretinib and another antifungal.

The claim language supplied appears to combine a pharmacokinetic result with a clinical monitoring instruction. The 99% AUC increase is not merely background information. It is written as a limitation of the claimed method and may become central to infringement and validity disputes.

How does the ripretinib-itraconazole interaction work?

Itraconazole is a strong CYP3A inhibitor. Ripretinib is metabolized primarily through CYP3A-related pathways, and inhibition of that pathway increases systemic exposure to ripretinib and its active metabolite. The QINLOCK prescribing information reports that coadministration with itraconazole increased ripretinib exposure, including an approximately 99% increase in AUC0-inf for ripretinib, while also increasing peak exposure.[2]

The clinical concern is dose-related toxicity. The QINLOCK label identifies adverse reactions including alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, palmar-plantar erythrodysesthesia syndrome, vomiting, and decreased appetite. Serious risks include cardiac dysfunction, photosensitivity, impaired wound healing, and cutaneous malignancies.[2]

The claim therefore links:

a known drug-drug interaction;
the approved 150 mg daily ripretinib regimen;
a quantified exposure increase; and
monitoring for resulting adverse events.

The claim does not expressly require that the physician reduce the ripretinib dose, discontinue itraconazole, or discontinue ripretinib. Monitoring is the required management step.

What is the likely claim construction of the 99% AUC limitation?

The 99% limitation is potentially the most important and most contestable feature of the claim.

A court could interpret the language as requiring that itraconazole administration cause an approximate doubling of ripretinib AUC0-inf relative to administration of ripretinib without itraconazole. The comparison requires two exposure conditions:

ripretinib administered with itraconazole; and
ripretinib administered without concurrent itraconazole.

The phrase "in the patient" may create an individualized requirement. A population-average pharmacokinetic result may not establish that every treated patient experiences exactly a 99% increase. In pharmaceutical patent practice, however, pharmacokinetic limitations are often interpreted in light of the specification and experimental variability. The operative question would be whether "99%" is an exact patient-specific requirement, an approximate clinical result, or a population-level mean.

Potential construction issues include:

Issue	Possible dispute
Exactness	Whether the claim requires exactly 99% or an approximately 99% increase
Measurement	Which analytical method and sampling schedule determine AUC0-inf
Comparator	Whether the comparator is the same patient without itraconazole or a matched control population
Timing	How long itraconazole must be administered before the AUC comparison
Monitoring	Whether routine adverse-event observation satisfies the claim
Causation	Whether the monitored adverse event must be attributable to the combination

The claim also uses the phrase "the adverse event" without identifying a particular event. That wording may be interpreted broadly, but it could create an indefiniteness issue if the patent does not identify the monitored adverse events with reasonable clarity.

Is the claim limited to the approved QINLOCK dose?

Yes. The supplied claim requires oral administration of 150 mg ripretinib daily. A regimen using 100 mg daily, 50 mg daily, intermittent dosing, or another non-equivalent dosage would not literally satisfy that limitation.

The limitation is commercially significant because 150 mg once daily is the standard approved QINLOCK dose for adults with advanced GIST after prior treatment with three or more kinase inhibitors, including imatinib.[2] The claim therefore tracks the marketed regimen rather than a development-stage or experimental dose.

The claim does not appear to cover:

150 mg twice-daily ripretinib;
alternate-day dosing;
dose reduction after toxicity;
ripretinib administered intravenously;
treatment of non-GIST cancers; or
treatment of GIST patients not taking itraconazole.

A doctrine-of-equivalents theory could be asserted for a clinically equivalent regimen, but the express 150 mg limitation and the highly specific pharmacokinetic result would make that theory fact-dependent.

What is the FDA regulatory status of ripretinib?

The FDA approved QINLOCK on May 15, 2020, for adults with advanced GIST who previously received treatment with three or more kinase inhibitors, including imatinib.[1] The approval was based primarily on the INVICTUS study, which evaluated ripretinib in patients with advanced GIST after prior kinase inhibitor therapy.[1]

The approved product is:

Product	Active ingredient	Sponsor	FDA status
QINLOCK	Ripretinib	Deciphera Pharmaceuticals	Approved
Dosage form	Oral tablets	Deciphera Pharmaceuticals	50 mg tablets; standard dose 150 mg daily
Indication	Advanced GIST after at least three prior kinase inhibitors, including imatinib	Deciphera Pharmaceuticals	Approved May 15, 2020

The FDA label warns against or recommends avoidance of strong and moderate CYP3A inhibitors where practicable because of increased ripretinib exposure. When coadministration cannot be avoided, the label directs clinicians to monitor patients more closely for adverse reactions.[2]

That regulatory language is closely aligned with the supplied patent claim. This alignment creates both commercial value and validity risk.

What is the Orange Book status of US Patent 11,969,414?

A patent’s inclusion in the FDA Orange Book depends on whether it claims the approved drug, an approved method of use, or an approved drug product characteristic and whether the NDA holder submits it for listing. A patent may be relevant to QINLOCK without necessarily appearing in the Orange Book.

The supplied information does not establish that US Patent 11,969,414 is listed in the Orange Book for QINLOCK. The patent’s apparent subject matter is a narrow coadministration and monitoring method involving itraconazole. If listed, it would most plausibly be classified as a method-of-use patent rather than a compound or formulation patent.

An Orange Book listing could expose an ANDA applicant to a Paragraph IV certification if the applicant seeks approval for a product whose proposed labeling includes the patented use. The risk is narrower if the proposed label omits itraconazole coadministration and does not instruct monitoring for the claimed interaction.

When does US Patent 11,969,414 expire?

The patent issued on April 23, 2024. The expiration date cannot be determined reliably from the patent number alone because US patent term depends on the earliest effective nonprovisional filing date, continuation and divisional relationships, terminal disclaimers, patent-term adjustment, and any patent-term extension.

For a patent issued from a standard utility application, the baseline term is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments.[3] A continuation patent can therefore expire on the same date as an earlier family member. A terminal disclaimer can also shorten the term.

The patent’s commercial life should be analyzed through its complete family and USPTO Patent Center record, not the issue date. The supplied claim alone does not establish a defensible expiration date.

How strong is the patent estate for ripretinib?

US Patent 11,969,414 appears to be a narrow addition to a broader ripretinib estate. Ripretinib protection may include several distinct categories:

Patent category	Typical subject matter	Relevance to 11,969,414
Compound patents	Ripretinib chemical structure and salts	Separate from the claimed method
Pharmaceutical compositions	Tablets, excipients, and dosage forms	Not covered by the supplied claim
Treatment patents	Use in GIST and other cancers	Potentially related but distinct
Dosing patents	Once-daily, dose escalation, or treatment sequencing	Separate claim scope
Drug-interaction patents	CYP3A inhibitors and exposure management	Directly relevant
Manufacturing patents	Synthesis, intermediates, and solid forms	Not covered by the supplied claim

The strength of this particular claim is mixed.

Strengths

The claim has several concrete limitations that can distinguish it from a generic GIST treatment claim:

advanced GIST;
concurrent itraconazole;
150 mg daily ripretinib;
a quantified 99% AUC increase; and
monitoring for adverse events.

Those features may limit the number of realistic infringing clinical protocols.

Weaknesses

The claim also tracks information that appears in the FDA label and clinical pharmacology materials. Public disclosure of the interaction before the relevant patent filing could support an anticipation or obviousness challenge. A defendant could argue that it would have been routine to monitor a patient after a known strong CYP3A inhibitor increased ripretinib exposure.

The result limitation may also be vulnerable. If the 99% increase is a pharmacokinetic consequence of known coadministration rather than a new therapeutic discovery, an accused party could challenge whether the limitation adds patentable weight.

The monitoring step presents another vulnerability. Routine monitoring for adverse reactions may be considered inherent in ordinary medical practice, particularly where the product label already recommends monitoring. The patent holder would argue that the claimed combination of dose, itraconazole exposure, quantified AUC increase, and targeted safety monitoring is a distinct clinical method.

What prior-art and validity issues affect the patent?

The principal validity questions are likely to involve anticipation, obviousness, written description, enablement, and indefiniteness.

Anticipation

A single prior-art reference could anticipate the claim if it disclosed all required elements before the relevant priority date. Relevant sources could include:

clinical pharmacology reports;
FDA review materials;
QINLOCK labeling;
conference abstracts;
published clinical-trial protocols;
drug-interaction studies;
patent applications in the same family; and
medical literature describing itraconazole and ripretinib coadministration.

The strongest anticipation reference would need to disclose not only the 99% AUC increase but also treatment of advanced GIST with 150 mg daily ripretinib and monitoring for adverse events.

Obviousness

An obviousness challenge would likely combine:

the known 150 mg ripretinib regimen;
the known CYP3A inhibition caused by itraconazole;
the reported increase in ripretinib exposure; and
standard clinical monitoring for toxicity.

The patent holder could respond that the claimed method identifies a specific exposure-management protocol for a specific patient population and that the exact 99% pharmacokinetic relationship was not predictable before the study.

Indefiniteness

Potential indefiniteness issues include:

the scope of "advanced gastrointestinal stromal tumor";
whether "99%" means exactly 99% or approximately 99%;
how AUC0-inf must be measured;
what constitutes "concurrent" administration;
what adverse event must be monitored; and
how causation between the combination and the adverse event is established.

Written description and enablement

The specification would need to support the claimed clinical combination, including the itraconazole interaction, the 150 mg dose, the AUC increase, and the monitoring instruction. A single clinical pharmacology study may support the AUC result, but broader patient-specific language could be challenged if the disclosure does not demonstrate the result across the full scope of patients.

Which companies are most likely to challenge the patent?

The direct commercial challengers would most likely be:

generic applicants seeking approval for ripretinib tablets;
companies pursuing 505(b)(2) applications involving ripretinib;
manufacturers seeking an authorized generic position;
parties developing alternative kinase inhibitors for post-imatinib GIST; and
clinical providers or payers disputing method-of-use enforcement in a narrow coadministration setting.

A conventional ANDA applicant may avoid direct infringement by using a carve-out label that omits the itraconazole coadministration and associated monitoring instructions, assuming the FDA permits the relevant use to be carved out. The risk increases if the proposed label retains broad language directing clinicians to monitor adverse reactions when ripretinib is used with strong CYP3A inhibitors.

What Paragraph IV risks exist for QINLOCK?

If US Patent 11,969,414 is listed in the Orange Book, an ANDA applicant could submit a Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed. The NDA holder could then bring a patent-infringement action within the statutory period, potentially triggering a 30-month stay of ANDA approval under the Hatch-Waxman framework.[4]

The practical Paragraph IV exposure is limited by the claim’s narrow requirements. A generic applicant could pursue one or more of these positions:

Strategy	Potential effect
Paragraph III certification	Delay approval until patent expiration
Paragraph IV certification	Challenge validity or infringement
Section viii carve-out	Omit the patented itraconazole-management use
Label design	Avoid instructing concurrent itraconazole administration
Dose differentiation	Use a regimen outside the 150 mg daily limitation, if clinically and regulatorily permissible

A label carve-out would not automatically eliminate all infringement theories. Liability could still arise if the manufacturer encourages the patented use through product labeling, promotional materials, medical-information responses, or clinical support programs.

What litigation and settlement agreements affect the patent?

The supplied information does not establish a reported infringement action, Paragraph IV litigation, or settlement agreement specifically involving US Patent 11,969,414. The patent issued in 2024, and its litigation significance depends on Orange Book listing, ANDA timing, and the filing of a generic application.

A settlement could include:

an agreed generic entry date;
a license to the patent;
a covenant not to sue;
a permitted label carve-out;
restrictions on promotion of itraconazole coadministration; or
a payment or supply arrangement.

No settlement terms should be attributed to this patent without a filed court document, FTC disclosure, SEC filing, or FDA-related record.

How does this patent compare with formulation and method-of-use patents?

US Patent 11,969,414 is a narrow pharmacokinetic and safety-management patent.

Patent type	Scope	Exposure to generic challenge
Compound patent	Covers the ripretinib molecule	Usually broad, but validity depends on prior art
Formulation patent	Covers tablet composition or release profile	Can block substitutable products if listed
Broad GIST-use patent	Covers use of ripretinib to treat GIST	Broad clinical relevance
Dose-regimen patent	Covers a particular dosing schedule	Depends on label and prescribing practice
Interaction-monitoring patent	Covers coadministration with itraconazole and monitoring	Narrow and easier to design around
Manufacturing patent	Covers synthesis or intermediates	May affect supply without directly blocking generic sale

The patent’s commercial value is therefore unlikely to equal that of a core compound or broad therapeutic-use patent. Its value is higher if the product label expressly directs clinicians to follow the claimed protocol and lower if clinicians generally avoid itraconazole or use alternative antifungal agents.

What generic launch scenarios exist?

Three launch scenarios are most plausible.

Full-label generic launch

A generic applicant challenges the relevant patent claims and obtains approval with labeling that includes the full ripretinib indication. This creates the greatest litigation exposure if the patent is listed and enforceable.

Carved-out launch

The applicant omits itraconazole-specific use and monitoring instructions under a Section viii statement. This may permit approval while avoiding direct inducement allegations, although the risk depends on the final label and promotional conduct.

Delayed launch or settlement

The applicant accepts a later entry date or licenses the patent. This preserves the branded product’s near-term revenue while allowing eventual generic competition.

What is the revenue exposure?

QINLOCK’s revenue exposure depends on the broader patent estate, not this claim alone. A narrow itraconazole-monitoring claim is unlikely by itself to prevent all generic ripretinib competition. It can still delay or complicate entry if:

it is listed in the Orange Book;
the approved label contains the claimed instructions;
a generic cannot practically carve out the use;
the patent survives validity challenges; and
the brand owner has other enforceable patents covering the compound, formulation, or broad GIST use.

Itraconazole is only one strong CYP3A inhibitor. A generic label that avoids itraconazole but still includes broad interaction warnings could face separate inducement arguments, although those arguments would not automatically satisfy this claim.

Key Takeaways

US Patent 11,969,414 is a narrow method-of-treatment patent.
The supplied claim requires advanced GIST, concurrent itraconazole, oral ripretinib at 150 mg daily, a 99% increase in ripretinib AUC0-inf, and adverse-event monitoring.
It does not broadly cover ripretinib, QINLOCK, GIST treatment, formulations, manufacturing, or all CYP3A inhibitor combinations.
The 99% AUC limitation is likely to be central to claim construction, infringement, and validity disputes.
The claim tracks FDA-recognized pharmacokinetic and safety information, which creates potential obviousness and inherent-result arguments.
The patent’s Orange Book status, terminal disclaimer status, priority chain, and expiration date cannot be established from the claim text alone.
A generic applicant may pursue a Paragraph IV challenge, a Section viii carve-out, or a label strategy that omits itraconazole-specific instructions.
The patent is more likely to supplement a broader ripretinib patent estate than to independently block all generic QINLOCK competition.
No specific litigation or settlement agreement involving US Patent 11,969,414 is established by the supplied record.

FAQs About US Patent 11,969,414

Does US Patent 11,969,414 cover QINLOCK itself?

No. The supplied claim covers a clinical method involving QINLOCK’s active ingredient, ripretinib, in a specific itraconazole coadministration and monitoring scenario.

Does the patent cover ripretinib with ketoconazole or clarithromycin?

Not on the supplied claim. The claim expressly identifies itraconazole. Other CYP3A inhibitors would require separate claim language or a viable doctrine-of-equivalents theory.

Can a physician infringe this patent by prescribing ripretinib and itraconazole?

Potentially, if the physician performs every claimed step, including the 150 mg daily dose, the concurrent itraconazole administration, the claimed exposure relationship, and monitoring for the relevant adverse event.

Does a 100 mg ripretinib dose avoid the claim?

It would avoid literal infringement of the supplied claim because the claim requires 150 mg daily. The patent holder could still evaluate other claims or an equivalence theory.

Is the 99% AUC increase required in every individual patient?

The claim language states the increase "in the patient." Whether that requires an exact patient-specific result or an approximate result established from pharmacokinetic data would depend on claim construction and the patent specification.

References

U.S. Food and Drug Administration. (2020, May 15). FDA approves Qinlock for advanced gastrointestinal stromal tumor. https://www.fda.gov
U.S. Food and Drug Administration. (2024). QINLOCK (ripretinib) prescribing information. Deciphera Pharmaceuticals, Inc.
United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
United States Code. (2024). 21 U.S.C. § 355(j): Abbreviated application for new drug.
United States Patent No. 11,969,414. (2024). Method of treating advanced gastrointestinal stromal tumor with ripretinib and itraconazole. U.S. Patent and Trademark Office.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Deciphera Pharms	QINLOCK	ripretinib	TABLET;ORAL	213973-001	May 15, 2020		RX	Yes	Yes	11,969,414	⤷ Start Trial				TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN PATIENTS BEING TREATED CONCURRENTLY WITH ITRACONAZOLE	⤷ 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
Argentina	122301	⤷ Start Trial
Australia	2020328538	⤷ Start Trial
Australia	2020329956	⤷ Start Trial
Australia	2023286024	⤷ Start Trial
Australia	2024259651	⤷ Start Trial
Brazil	112022002609	⤷ Start Trial
Canada	3150433	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,969,414

Which drugs does patent 11,969,414 protect, and when does it expire?

Summary for Patent: 11,969,414