United States Patent 10,966,966: Ripretinib Claim Scope, Exclusivity and Patent Landscape

U.S. Patent No. 10,966,966 protects a narrow method of using ripretinib, marketed as QINLOCK, in adults with advanced gastrointestinal stromal tumor (GIST) after failure of imatinib, sunitinib and regorafenib. The principal claim requires a 150 mg once-daily oral dose and a six-month progression-free-survival result measured under mRECIST 1.1. Dependent claims protect dose interruption and reduction protocols for Grade 2 or Grade 3 palmar-plantar erythrodysesthesia syndrome.

The patent is a late-stage clinical-use patent rather than a compound patent. Its practical value is tied to QINLOCK's approved fourth-line GIST use, the FDA label, Orange Book listing status, and the difficulty a generic applicant would face in designing a non-infringing label for the same patient population.

What does U.S. Patent 10,966,966 protect?

U.S. Patent 10,966,966 protects a treatment method with five cumulative elements:

The patient has advanced GIST.
The tumor has progressed after imatinib, sunitinib and regorafenib.
Ripretinib is administered orally at 150 mg once daily.
Treatment continues for at least 28 days.
The patient achieves six months of progression-free survival under mRECIST 1.1.

The patent therefore does not cover every use of ripretinib, every GIST patient, or every dose. It targets the patient population corresponding to the established fourth-line treatment sequence for advanced GIST.

Patent profile

Field	Information
U.S. patent	10,966,966
Patent holder/assignee	Deciphera Pharmaceuticals, LLC
Product	Ripretinib, marketed as QINLOCK
Therapeutic area	Advanced gastrointestinal stromal tumor
Primary claim type	Method of treatment
Core dose	150 mg orally once daily
Covered treatment sequence	Imatinib, then sunitinib, then regorafenib, followed by ripretinib
Clinical outcome	Six months of progression-free survival
Response framework	mRECIST 1.1
Grant date	March 30, 2021
Expected nominal patent expiration	May 2037, subject to terminal-disclaimer and patent-term-adjustment analysis
Regulatory product	QINLOCK tablets
FDA approval	May 15, 2020

The patent's expiration date should be read from the current USPTO patent record and FDA Orange Book listing. The commonly reported nominal expiration for this family is in May 2037. Patent-term adjustment, terminal disclaimer, pediatric extension and Orange Book coding can affect the operative exclusivity date.

How broad is claim 1 of U.S. Patent 10,966,966?

Claim 1 is clinically important but legally narrow. It is limited by the treatment history, dose, route, treatment duration and clinical outcome.

Patient-history limitation

The patient must have progressed after all three prior therapies:

First line: imatinib
Second line: sunitinib
Third line: regorafenib

A patient who received these drugs in a different order may not satisfy the literal sequence limitation. The claim also appears directed to tumor progression from those treatments, rather than simple prior exposure.

This limitation creates a meaningful design-around issue. A competing product used after imatinib, sunitinib and another fourth-line therapy might avoid literal infringement if the third-line regorafenib requirement is not met. The commercial value of that strategy would depend on whether the alternative regimen is clinically accepted and consistent with the FDA-approved indication.

Dose and route limitation

The claim requires oral administration of 150 mg daily. An accused use involving 100 mg daily, intermittent administration, or a materially different route would not meet the literal dose limitation. A generic product would still face infringement risk if its labeling instructs patients to begin at 150 mg once daily and reduce the dose for toxicity.

Outcome limitation

The requirement that the patient achieves six months of progression-free survival is unusual because it is framed as a patient outcome rather than solely as an instruction to administer the drug.

This limitation may affect infringement analysis in two ways:

A treatment instruction can be read as requiring administration under conditions intended to produce the specified outcome.
The patent holder may need to establish that the treated patient actually met the six-month progression-free-survival limitation, depending on claim construction and the relevant infringement theory.

The reference to mRECIST 1.1 supplies a measurement framework but does not eliminate factual disputes over imaging dates, progression criteria, censoring, death, treatment discontinuation and assessment intervals.

28-day limitation

The patient must receive at least 28 days of daily ripretinib administration before the claimed result is satisfied. A brief administration that does not continue for 28 days would not meet the express duration requirement, although repeated prescribing and treatment records could become relevant in an infringement dispute.

What do claims 2 and 3 protect?

Claims 2 and 3 protect toxicity-management protocols for palmar-plantar erythrodysesthesia syndrome, also called hand-foot syndrome. Both claims depend on claim 1 and therefore inherit all of claim 1's limitations.

Claim 2: Grade 3 toxicity

Claim 2 requires:

Grade 3 palmar-plantar erythrodysesthesia syndrome;
withholding ripretinib for at least seven days, or until the condition improves to Grade 1 or less;
resuming treatment at 100 mg daily;
continuing the 100 mg dose for at least 28 days.

This claim covers a defined interruption-and-reduction sequence. It does not cover every 100 mg ripretinib regimen because the sequence must follow the claimed Grade 3 event and withholding step.

Claim 3: Grade 2 toxicity

Claim 3 requires:

Grade 2 palmar-plantar erythrodysesthesia syndrome;
withholding ripretinib until recovery to Grade 1 or less, or baseline;
resuming at 150 mg daily if recovery occurs within seven days;
reducing to 100 mg daily if recovery does not occur within seven days;
administering the relevant dose for at least 28 days.

Claim 3 is more operationally complex than claim 2. It protects a conditional dose-management algorithm based on the speed of recovery.

Claim hierarchy and scope

Claim	Covered conduct	Relative scope
1	Fourth-line ripretinib at 150 mg daily in advanced GIST	Broadest claim in the patent, but still clinically narrow
2	Grade 3 toxicity, treatment interruption, then 100 mg daily	Narrower
3	Grade 2 toxicity, recovery-based decision, 150 mg or 100 mg daily	Narrowest and most fact-dependent

What FDA indication does the patent align with?

The FDA approved QINLOCK for adults with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. The approval was based principally on the INVICTUS study, which evaluated ripretinib in patients with advanced GIST after at least three prior kinase inhibitors.

The FDA-approved dose is 150 mg orally once daily. The label also provides dose-modification instructions for adverse reactions, including palmar-plantar erythrodysesthesia syndrome.[1]

The claim language tracks the commercial fourth-line GIST use but is more specific than the FDA indication in several respects. The FDA indication requires prior treatment with three or more kinase inhibitors, including imatinib, while claim 1 expressly identifies imatinib, sunitinib and regorafenib and specifies a treatment sequence.

What patents protect QINLOCK and ripretinib?

U.S. Patent 10,966,966 is one component of a broader QINLOCK patent estate. The estate has included compound, pharmaceutical-composition, formulation, crystalline-form, manufacturing and method-of-use rights.

Principal patent categories

Patent category	Commercial purpose	Relevance to generic entry
Ripretinib compound patents	Protect the active chemical entity	Typically the strongest barrier while unexpired
Salt, polymorph or crystalline-form patents	Protect physical forms used in manufacture or formulation	May complicate sourcing and ANDA product design
Pharmaceutical-composition patents	Protect tablets or compositions containing ripretinib	Can create formulation-specific infringement risk
Method-of-treatment patents	Protect use in GIST and other indications	Relevant to Paragraph IV and skinny-label strategy
Dose-management patents	Protect dose interruption and reduction for toxicity	May affect prescribing instructions and labeling
Manufacturing patents	Protect production routes and intermediates	Can create process risk without necessarily blocking a finished-dose product

The exact Orange Book patent list should be distinguished from the complete worldwide patent family. A patent can be commercially relevant without being listed in the Orange Book, and an Orange Book listing does not establish validity or infringement.

What is the Orange Book status of U.S. Patent 10,966,966?

U.S. Patent 10,966,966 has been associated with QINLOCK's U.S. patent protection and is relevant to the FDA-listed exclusivity position for ripretinib tablets. The listing category is expected to be a method-of-use patent rather than a composition-of-matter patent.

For an ANDA applicant, the key questions are whether the patent is listed for the relevant QINLOCK strength and dosage form, whether the proposed label includes the patented fourth-line use, and whether the applicant submits:

Paragraph I certification: no patent information has been submitted;
Paragraph II certification: the patent has expired;
Paragraph III certification: the applicant will wait until expiration; or
Paragraph IV certification: the patent is invalid, unenforceable or will not be infringed.

A Paragraph IV certification would generally trigger notice to the patent holder and could initiate the Hatch-Waxman litigation process. A timely infringement action can impose a statutory 30-month stay on FDA approval, subject to the statutory exceptions and court decisions.[2]

When does ripretinib lose exclusivity?

Ripretinib's principal U.S. exclusivity layers are separate from patent expiration.

Exclusivity layer	Relevant date or period
FDA approval	May 15, 2020
New chemical entity exclusivity	Five years from approval, subject to Paragraph IV timing rules
Orphan-drug exclusivity	Seven years for the approved orphan indication, subject to statutory exceptions
Patent 10,966,966	Nominally May 2037
Generic entry	Potentially before patent expiry if patents are invalidated, not infringed, delisted, or settled on terms permitting earlier launch

The orphan-drug exclusivity period is particularly important. FDA orphan exclusivity generally prevents approval of the same drug for the same disease or condition for seven years, absent statutory exceptions. Because QINLOCK was approved for an orphan indication, that exclusivity period extended beyond the five-year new chemical entity period.[3]

Patent protection, rather than regulatory exclusivity, is the principal long-term barrier associated with Patent 10,966,966.

How strong is the patent estate for ripretinib?

The estate has moderate-to-strong commercial value but uneven litigation strength.

Strengths

The patent covers the commercially approved dose of 150 mg daily.
The claimed patient population closely matches QINLOCK's established fourth-line GIST market.
The treatment sequence is clinically recognizable and can be reflected in prescribing and labeling.
Claims 2 and 3 protect practical toxicity-management steps that appear in the product label.
The expiration date extends well beyond the initial FDA approval and orphan-exclusivity periods.

Vulnerabilities

Claim 1 is limited by a specific sequence of prior therapies.
The six-month progression-free-survival limitation may create claim-construction and proof issues.
The claim does not cover all ripretinib patients or all GIST treatment lines.
A generic applicant may attempt a section viii, or skinny-label, carve-out for the patented method if the FDA-listed use can be removed without undermining the remaining approved indications.
Dependent claims 2 and 3 require specific adverse-event grades, recovery periods and dose changes, creating fact-intensive infringement questions.

The most valuable commercial element is the alignment between the patent's patient population and the fourth-line GIST label. The most significant legal vulnerability is the outcome and treatment-history language.

What generic launch risks exist for ripretinib?

A generic launch would likely follow an ANDA pathway because ripretinib is a small molecule, not a biologic. Biosimilar approval under section 351(k) is not the relevant pathway.

Scenario 1: Paragraph III certification

The applicant accepts the patent and waits until the relevant patent expiry date. This minimizes litigation risk but delays entry until the listed patent barrier ends.

Scenario 2: Paragraph IV challenge

The applicant argues that Patent 10,966,966 is invalid, unenforceable or not infringed. Potential arguments could focus on:

Obviousness based on prior clinical knowledge of ripretinib dosing and fourth-line GIST;
Written-description or enablement support for the six-month progression-free-survival limitation;
Definiteness of the outcome, mRECIST 1.1 and 28-day language;
Non-infringement based on a label that omits the claimed sequence or dose-management instructions;
Failure to satisfy all limitations in actual patient treatment.

Scenario 3: Skinny-label launch

A generic applicant may seek approval for uses not covered by listed method patents. The commercial feasibility depends on whether the remaining label still supports a viable market and whether the FDA permits the proposed carve-out.

For QINLOCK, a skinny-label strategy would be difficult if the principal commercial indication is the same fourth-line GIST population covered by claim 1. The patent's method limitations track that indication closely.

Scenario 4: At-risk launch

A generic applicant could launch before final resolution of patent litigation. That approach exposes the applicant to damages, a potential injunction, and enhanced damages risk if infringement is found. It is generally less attractive where the patent covers the primary commercial indication.

Which companies are challenging ripretinib exclusivity?

No major biosimilar challenge is expected because ripretinib is a chemically synthesized small molecule. The relevant challengers would be generic-drug manufacturers filing ANDAs, not biosimilar developers.

Public FDA approval materials and the patent record identify Deciphera as the original sponsor and patent holder associated with QINLOCK. Following Ono Pharmaceutical's acquisition of Deciphera in 2024, Ono became the corporate owner of Deciphera's business and QINLOCK commercial rights.[4]

A definitive list of ANDA applicants and Paragraph IV challengers must be taken from FDA paragraph-IV notices, district-court dockets and the current Orange Book. Patent 10,966,966 itself does not establish that a particular generic company has filed a challenge.

What litigation affects U.S. Patent 10,966,966?

The patent's principal litigation relevance arises under the Hatch-Waxman framework. A Paragraph IV notice concerning a listed QINLOCK patent could produce an infringement action under 35 U.S.C. §271(e)(2).

The main litigation issues would likely be:

Issue	Expected dispute
Claim construction	Meaning of “progressed from” each prior therapy
Treatment sequence	Whether the therapies must be administered in the stated order
Outcome limitation	Whether six-month progression-free survival is an enforceable claim limitation
Measurement standard	Application of mRECIST 1.1
Dose infringement	Whether proposed labeling instructs 150 mg daily use
Dose modification	Whether label instructions practice claims 2 or 3
Validity	Obviousness, written description, enablement and definiteness
Remedy	Injunction, damages and possible launch restrictions

No settlement terms should be inferred from the existence of the patent or from FDA listing data. A settlement would require a public court filing, consent judgment, or authorized company disclosure.

How does Patent 10,966,966 compare with a compound patent?

A compound patent generally has broader enforcement reach because it can cover manufacture, sale, importation and use of the active ingredient across indications and dosage forms. Patent 10,966,966 is narrower because it covers only a defined treatment method.

Attribute	Compound patent	U.S. 10,966,966
Covered subject	Ripretinib molecule or defined chemical form	Clinical use and dose regimen
Patient limitation	Usually none	Advanced GIST after three named therapies
Dose limitation	Usually none	150 mg daily
Outcome requirement	Usually none	Six months of PFS
Design-around potential	Lower	Higher
Relevance to skinny label	Limited	High
Typical commercial role	Core molecule protection	Supplemental life-cycle protection

The patent can still delay generic entry when the protected method is the primary or only commercially valuable indication.

What geographic coverage does the ripretinib estate have?

Patent 10,966,966 is a U.S. patent and protects conduct occurring within the United States, including U.S. sales and use covered by the patent's method claims. Separate patent families may exist in Europe, Japan, China, Canada and other jurisdictions.

Deciphera entered a Greater China collaboration with Zai Lab for ripretinib development and commercialization. That arrangement affected regional commercial rights but did not transfer the U.S. patent's territorial scope.[5]

Geographic risk therefore depends on:

National patent expiration dates;
Local claim scope;
Regulatory approval timing;
National patent-term adjustments or supplementary protection certificates;
Local patent-linkage rules;
License and commercialization arrangements.

What manufacturing and IP barriers remain after Patent 10,966,966?

Even if a generic avoids the method claims, it may face separate risks involving:

The ripretinib active ingredient;
Crystalline or solid-state forms;
Tablet composition;
Manufacturing intermediates;
Process patents;
Impurity-control specifications;
FDA-approved labeling and dose-modification language.

A finished-dose manufacturer can avoid some process patents by using an independent manufacturing route. It cannot safely assume that avoiding the method patent eliminates all patent exposure.

Key Takeaways

U.S. Patent 10,966,966 is a method-of-treatment patent for ripretinib in advanced GIST after imatinib, sunitinib and regorafenib.
Claim 1 requires oral 150 mg daily administration, at least 28 days of treatment and six months of PFS under mRECIST 1.1.
Claims 2 and 3 protect dose interruption and reduction protocols for Grade 3 and Grade 2 palmar-plantar erythrodysesthesia syndrome.
The patent closely tracks QINLOCK's fourth-line GIST commercial use, making a complete skinny-label carve-out commercially difficult.
Its nominal expiration is reported in May 2037, subject to the operative USPTO and Orange Book records.
The patent is narrower and more fact-dependent than a compound patent because it requires a particular patient history, dose and clinical result.
Generic challenges would proceed through the ANDA and Paragraph IV framework, not the biosimilar pathway.
The key validity and infringement issues are the treatment-sequence requirement, the six-month PFS limitation, mRECIST 1.1, and the dose-modification instructions.

FAQs About U.S. Patent 10,966,966

Does U.S. Patent 10,966,966 cover all QINLOCK prescriptions?

No. It covers a specific advanced-GIST treatment sequence, 150 mg daily dose, treatment duration and clinical outcome. It does not automatically cover every ripretinib prescription.

Can a generic sell ripretinib for an indication outside advanced GIST?

Potentially, subject to other unexpired patents, FDA labeling requirements and applicable regulatory restrictions. Patent 10,966,966 is limited to the claimed GIST method.

Does the patent cover 100 mg ripretinib as an initial dose?

Generally no. The dependent claims address 100 mg dosing only after the claimed toxicity-related withholding and dose-management steps.

Is the six-month progression-free-survival requirement difficult to enforce?

It may be. The limitation creates factual questions involving actual patient outcomes, imaging assessments, mRECIST 1.1 and the relationship between prescribing instructions and results.

Who owns the commercial rights associated with QINLOCK?

Deciphera developed QINLOCK, and Ono Pharmaceutical acquired Deciphera in 2024. Regional rights, including Greater China arrangements, may be governed by separate collaboration agreements.

References

U.S. Food and Drug Administration. (2020). QINLOCK (ripretinib) prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
U.S. Food and Drug Administration. (n.d.). Orphan drug designation and exclusivity. FDA.
Ono Pharmaceutical Co., Ltd. (2024). Completion of acquisition of Deciphera Pharmaceuticals, Inc. Ono Pharmaceutical.
Zai Lab Limited. (2019). Zai Lab and Deciphera Pharmaceuticals collaboration for ripretinib in Greater China. Zai Lab.
U.S. Patent No. 10,966,966. (2021). Methods of treating gastrointestinal stromal tumors with ripretinib. United States 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	⤷ Start Trial	⤷ Start Trial				TREATMENT OF ADVANCED GASTROINTESTINAL STROMAL TUMOR IN PATIENTS HAVING PROGRESSED FROM A FIRST LINE ADMINISTRATION OF IMATINIB, A SECOND LINE ADMINISTRATION OF SUNITINIB, AND A THIRD LINE ADMINISTRATION OF REGORAFENIB	⤷ 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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,966,966