United States Patent 12,059,410: Ripretinib Patent Scope, Claims, Expiration Risk, and Competitive Landscape

U.S. Patent No. 12,059,410 covers a narrow method of treating advanced gastrointestinal stromal tumor, or GIST, with 150 mg of oral ripretinib administered daily after progression on imatinib, sunitinib, and regorafenib. The claims also require a progression-free survival outcome measured under mRECIST 1.1 after at least 42 days of therapy. The patent is directed to QINLOCK’s post-line-3 use rather than to ripretinib’s chemical composition, tablet formulation, or general use in GIST.

The principal commercial risk is a labeled or promoted generic use that reproduces the treatment sequence and 150 mg daily regimen. The principal legal vulnerabilities are claim construction, enablement and written-description challenges concerning the PFS limitations, and the question whether the claimed clinical outcome is a limiting method element or an inherent result of practicing the dosing regimen.

What does U.S. Patent 12,059,410 protect?

The patent protects a treatment method with five material requirements:

Claim element	Requirement
Disease	Advanced gastrointestinal stromal tumor
Prior treatment	Progression after imatinib, sunitinib, and regorafenib
Administration	Oral administration
Dose	Three tablets daily, each containing 50 mg ripretinib, for a total of 150 mg
Clinical result	More than three months of PFS under mRECIST 1.1 after at least 42 days of daily ripretinib
Dependent result	Claim 2 raises the PFS threshold to more than six months

Claim 1 is a method-of-treatment claim. It does not claim ripretinib as a molecule, the 50 mg tablet as a composition, or every use of ripretinib in GIST. Claim 2 narrows claim 1 by requiring the greater-than-six-month PFS result.

The claim corresponds to the clinical setting in which QINLOCK is used after prior treatment with the three approved kinase inhibitors. FDA approved ripretinib for adults with advanced GIST who previously received treatment with three or more kinase inhibitors, including imatinib.[2]

How narrow are the claims of U.S. Patent 12,059,410?

The claims are narrow in patient selection but potentially broad in the way the clinical outcome is expressed.

A practicing physician would need to treat a patient whose tumor progressed from the specified sequence of therapies. A patient who previously received imatinib, sunitinib, and regorafenib in a different order may fall outside the literal wording of claim 1 because the claim recites first-line imatinib, second-line sunitinib, and third-line regorafenib.

The claim also specifies three 50 mg tablets. A 150 mg dose delivered as one 150 mg tablet, six 25 mg tablets, or another dosage form could raise a literal-infringement issue. Whether such an alternative would infringe under the doctrine of equivalents would depend on the prosecution history, the patent specification, and the significance of the tablet-count limitation.

The clinical-outcome language creates a separate scope issue. Claim 1 requires that the treatment provide more than three months of PFS after at least 42 days of therapy. Claim 2 requires more than six months. The wording does not expressly state that every treated patient must achieve the result. It reads as a population-level outcome limitation, although the precise construction would depend on the patent specification and prosecution history.

What is the difference between claim 1 and claim 2?

Claim 2 is a narrower species of claim 1.

Feature	Claim 1	Claim 2
Required PFS	More than 3 months	More than 6 months
Minimum administration period	At least 42 days	At least 42 days through claim 1
Patient sequence	Required	Required
Daily dose	150 mg	150 mg
Dosage form	Three 50 mg tablets	Three 50 mg tablets

A product or treatment that satisfies claim 2 necessarily satisfies claim 1, assuming the remaining limitations are met. A treatment producing between three and six months of PFS could fall within claim 1 but outside claim 2.

The six-month limitation may provide a narrower enforcement position, but it can also create additional validity questions if the asserted clinical data do not clearly support that threshold across the full scope of the claim.

What clinical evidence supports the ripretinib claims?

The relevant clinical setting is the INVICTUS trial population, which included patients with advanced GIST previously treated with imatinib, sunitinib, and regorafenib. Ripretinib was administered at 150 mg once daily. The trial demonstrated a progression-free survival benefit compared with placebo in this heavily pretreated population.[3]

FDA’s QINLOCK labeling identifies the approved dosage as 150 mg orally once daily and the approved indication as advanced GIST after prior treatment with three or more kinase inhibitors, including imatinib.[2]

The patent claims use mRECIST 1.1, a modified response-assessment framework commonly used for GIST because tumor density and morphology can change without immediate size reduction. The use of a specified assessment standard limits disputes over how progression is measured, although it can create evidentiary disputes over imaging review, censoring, missing scans, and independent versus investigator assessment.

When does U.S. Patent 12,059,410 lose exclusivity?

The patent’s terminal expiration date cannot be established from the claim text alone. The relevant date depends on the patent’s earliest effective nonprovisional priority date, patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable disclaimer or disclaimer-related prosecution record.[1]

Because the claimed use is associated with the post-line-3 QINLOCK indication, the patent is likely part of a later ripretinib method-of-use family rather than the earliest composition-of-matter family. A later-filed method patent can extend practical protection beyond the expiration of an earlier compound patent, subject to patent-term rules.

For commercial planning, the relevant exclusivity stack should be separated into:

Protection layer	Commercial function
Compound patent	Protects ripretinib as an active pharmaceutical ingredient
Composition or formulation patents	Protect the tablet, solid form, excipients, or manufacturing process
Method-of-use patents	Protect treatment of defined GIST populations
Regulatory exclusivity	Restricts approval of competing applications for a defined period
Orange Book listings	Provide notice of listed patents and support a potential patent certification dispute

The Orange Book listing and USPTO patent record, rather than the claim language alone, control the operative Hatch-Waxman dates.[4][5]

What is the Orange Book status of U.S. Patent 12,059,410?

An Orange Book listing would matter only if the patent is listed against the approved QINLOCK drug product and FDA accepts that it claims the approved drug, an approved method of using the drug, or a qualifying drug substance or product.

For a method-of-use patent, the relevant listing would generally identify the approved use protected by the patent. A generic applicant submitting a Paragraph IV certification against a listed patent could trigger the statutory litigation framework if the NDA holder or patent owner files suit within the applicable period.[5]

The patent’s practical Orange Book significance depends on:

Whether it is listed against QINLOCK.
Whether the listed use corresponds to the generic applicant’s proposed labeling.
Whether the applicant files a Paragraph III certification, Paragraph IV certification, or a section viii statement.
Whether FDA permits a carve-out of the protected use from the generic label.
Whether the NDA holder sues within the statutory filing period.

The existence of an issued patent does not by itself establish Orange Book listing, a 30-month stay, or a viable infringement case. Those consequences depend on the listing and the ANDA filing record.

Could a generic applicant challenge U.S. Patent 12,059,410 under Paragraph IV?

Yes. A generic applicant seeking approval of ripretinib tablets could challenge the patent with a Paragraph IV certification if the patent is listed and the applicant contends that the patent is invalid, unenforceable, or not infringed.

The most relevant challenge theories would be the following:

Noninfringement

A generic applicant could design its label or formulation around one or more limitations, including:

A dosing regimen other than three 50 mg tablets daily.
A dosage form that does not contain three 50 mg tablets.
A label that omits the post-imatinib, post-sunitinib, post-regorafenib sequence.
A section viii carve-out excluding the patented post-line-3 use, if FDA permits the carve-out and the remaining label is commercially viable.
A regimen that does not recommend daily administration.

A label omitting the use does not eliminate all induced-infringement risk if the manufacturer markets the product through instructions, promotional materials, training, or other conduct encouraging the patented use.

Invalidity for lack of written description or enablement

The PFS limitations may attract scrutiny if the specification discloses clinical evidence for the claimed outcome only in a narrow subgroup but the claim reaches a broader population. The analysis would focus on whether the patent reasonably demonstrates possession of the claimed treatment method and whether the disclosure enables the full claimed scope without undue experimentation.[1]

Indefiniteness

Potential issues include the meaning of:

“Advanced” GIST.
“Progressed from” each prior therapy.
“More than 3 months” or “more than 6 months” of PFS.
“After at least 42 days.”
PFS “in patients” as a population-level limitation.
The required application of mRECIST 1.1.

A court could construe these terms using the specification, incorporated clinical protocols, prosecution record, and expert testimony. The use of a recognized response standard reduces, but does not eliminate, indefiniteness risk.

Obviousness

An obviousness challenge could combine known ripretinib dosing, known treatment sequencing in advanced GIST, and clinical data showing activity after failure of approved kinase inhibitors. The patent owner would likely rely on the specific clinical result, the difficulty of treating fourth-line GIST, and the claimed PFS threshold as evidence against obviousness.

The strength of that defense would depend on the priority date, pre-filing clinical disclosures, trial results available before the effective filing date, and the level of predictability in the field.

What patent landscape surrounds ripretinib and QINLOCK?

Ripretinib protection is likely to include several overlapping families rather than a single patent. The landscape should be separated into the following categories:

Patent category	Scope	Relevance to U.S. 12,059,410
Chemical compound patents	Ripretinib molecule and related compounds	Distinct from the asserted method
Pharmaceutical compositions	Ripretinib dosage forms and excipients	May block tablet design-arounds
Solid-state or polymorph patents	Crystal forms, salts, or physical forms	Relevant to manufacturing and formulation
Treatment-method patents	GIST, KIT, PDGFRA, and resistant tumors	Includes the claimed post-line-3 regimen
Combination patents	Ripretinib with other anticancer agents	Separate infringement analysis
Manufacturing patents	Synthesis, purification, and intermediate processes	May affect supply-chain freedom to operate
Regulatory patents	Orange Book-listed approved uses	Relevant to ANDA certification and launch timing

The most important distinction is between a patent that protects ripretinib itself and a patent that protects the QINLOCK indication. A generic may be unable to practice the compound patent before its expiration even if it defeats the method patent. Conversely, expiration or invalidation of a compound patent does not necessarily eliminate method-of-use or formulation barriers.

How strong is the patent estate for QINLOCK?

The estate is strongest where multiple rights cover independent commercial steps:

The active ingredient.
The approved 150 mg daily regimen.
The post-line-3 GIST population.
The commercial tablet formulation.
The manufacturing process.

U.S. Patent 12,059,410 is strongest against a product labeled expressly for the FDA-approved post-line-3 GIST population and dosed as 150 mg once daily in three 50 mg tablets. Its scope is weaker against:

Unlabeled sale with no inducement evidence.
A label that lawfully carves out the protected use.
Alternative dosing or tablet configurations.
Patients outside the recited treatment sequence.
Uses in other tumors or earlier lines of therapy.

The patent’s commercial value therefore depends heavily on how FDA-approved generic labeling is constructed and how QINLOCK’s other listed patents expire.

What generic launch scenarios exist?

Three launch scenarios are commercially plausible.

Full-label launch after patent clearance

A generic applicant may seek a label covering the same post-line-3 GIST use. This creates the highest Paragraph IV and induced-infringement exposure because the proposed label would closely track the patented method.

Carved-out launch

The applicant may attempt to remove the patented post-line-3 indication under a section viii statement. A carve-out is commercially useful only if the remaining label supports a substantial noninfringing market and FDA accepts the proposed language.

At-risk launch

A generic may launch before final resolution of litigation after a favorable district-court decision, settlement, or perceived weakness in the patent estate. This exposes the applicant to damages, an injunction, and potential launch disruption if the patent is later upheld.

Because claim 1 tracks the approved fourth-line treatment setting, a complete carve-out could remove much of the product’s principal market. That increases the likelihood that the patent would be litigated rather than avoided, assuming the patent is Orange Book-listed.

What patent litigation and settlement issues matter?

The key litigation questions are:

Whether U.S. Patent 12,059,410 is listed in the Orange Book.
Whether an ANDA applicant has filed a Paragraph IV certification.
Whether the patent owner filed an infringement action within the statutory period.
Whether the case was dismissed, stayed, settled, or adjudicated.
Whether any settlement includes a licensed entry date, authorized generic arrangement, supply agreement, or restriction on launch.
Whether the settlement was submitted to the Federal Trade Commission under the pharmaceutical patent-settlement reporting framework.

No litigation or settlement conclusion should be inferred from the patent’s issuance alone. The relevant evidence is the FDA Orange Book, ANDA litigation docket, district-court pleadings, Federal Circuit decisions, and FTC settlement filings.

Are biosimilars relevant to ripretinib?

No. Ripretinib is a small-molecule kinase inhibitor, not a biologic. Biosimilar approval under the Public Health Service Act does not apply. Competition would arise through the ANDA pathway for a generic small-molecule drug, subject to Hatch-Waxman patent certifications and FDA requirements.[5]

The relevant competitors are generic ripretinib manufacturers and, therapeutically, alternative kinase inhibitors used in GIST. The principal branded comparators are imatinib, sunitinib, and regorafenib, which occupy earlier lines of treatment or different treatment positions. QINLOCK’s differentiated market position is its use after failure of those agents.

What manufacturing and geographic barriers remain?

The U.S. patent does not automatically protect the product outside the United States. Geographic protection must be assessed family by family in jurisdictions such as the European Union, Japan, China, Canada, South Korea, and Australia.

Manufacturing risk can persist after a U.S. use patent expires if separate patents cover:

Ripretinib intermediates.
Synthetic routes.
Purification steps.
Solid forms.
Tablet manufacture.
Scale-up or process controls.

A foreign affiliate or contract manufacturer may also face separate process-patent exposure. A U.S. generic importing product made abroad can create additional risk under 35 U.S.C. § 271(g) if the product is made by a patented process.

What revenue exposure does U.S. Patent 12,059,410 create?

The patent directly covers the principal FDA-approved treatment setting for QINLOCK: adults with advanced GIST after prior treatment with at least three kinase inhibitors, including imatinib.[2] That makes the patent commercially significant even though its patient population is narrow.

Revenue exposure depends on the combined expiration profile of:

Composition patents.
Formulation patents.
Method-of-use patents.
Regulatory exclusivity.
Generic filing and launch timing.
The availability of a commercially viable label carve-out.

A challenge to U.S. Patent 12,059,410 alone may not produce immediate generic entry if another valid, unexpired patent blocks the same product or use. Conversely, if this patent is the principal remaining barrier to the approved indication, a successful Paragraph IV challenge could materially accelerate competition.

Key Takeaways

U.S. Patent 12,059,410 is a narrow method-of-treatment patent for 150 mg daily ripretinib in advanced GIST after progression on imatinib, sunitinib, and regorafenib.
Claim 1 requires more than three months of PFS under mRECIST 1.1 after at least 42 days of treatment.
Claim 2 narrows the outcome requirement to more than six months of PFS.
The patent does not, based on the supplied claims, claim ripretinib itself or every ripretinib use.
The most important infringement risk is a generic label that reproduces the approved post-line-3 GIST use.
The most important validity issues concern written description, enablement, obviousness, and construction of the PFS limitations.
Ripretinib is a small molecule, so biosimilar competition is irrelevant; the expected pathway is an ANDA.
A complete market-entry assessment requires review of the full ripretinib patent family, Orange Book listings, FDA exclusivity, and any ANDA litigation or settlement record.
The patent’s terminal expiration date cannot be derived from the claim language alone and must be determined from the USPTO patent-term record.

FAQs About U.S. Patent 12,059,410

Does the patent cover all QINLOCK prescriptions?

No. The supplied claims require a specific advanced-GIST treatment sequence, a 150 mg daily regimen delivered as three 50 mg tablets, and the specified PFS result.

Could a generic sell ripretinib for an earlier line of GIST treatment?

Potentially, if the proposed label and marketing do not encourage the patented post-line-3 use and no other patent blocks the earlier-line use. FDA labeling and inducement evidence would control the risk.

Does using a different number of tablets avoid infringement?

It may avoid literal infringement of the three-tablet limitation, but the result would depend on claim construction, prosecution history, and possible doctrine-of-equivalents arguments.

Is the six-month PFS requirement independently enforceable?

Yes. Claim 2 is an independent additional limitation that can be asserted separately from claim 1, subject to proof that the claimed treatment produces the required outcome under the applicable construction.

Can FDA approve a generic while the patent remains unexpired?

Yes, depending on the certification, litigation status, statutory stay, patent listing, settlement, and approval date. FDA approval and commercial launch are separate questions.

References

United States Patent and Trademark Office. (2024). U.S. Patent No. 12,059,410: Claims and patent record for ripretinib treatment of advanced gastrointestinal stromal tumor.
U.S. Food and Drug Administration. (2024). QINLOCK (ripretinib) prescribing information. Deciphera Pharmaceuticals, Inc.
Blay, J.-Y., Serrano, C., Heinrich, M. C., Zalcberg, J., Bauer, S., Gelderblom, H., Schöffski, P., Borden, E. C., Zintl, P., Le Cesne, A., Schütte, J., Chawla, S., & Casali, P. G. (2020). Ripretinib in patients with advanced gastrointestinal stromal tumours after failure of imatinib, sunitinib, and regorafenib (INVICTUS): A double-blind, randomised, placebo-controlled, phase 3 trial. The Lancet Oncology, 21(7), 923-934.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355; 35 U.S.C. §§ 156, 271, 282.

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
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: 12,059,410

Which drugs does patent 12,059,410 protect, and when does it expire?

Summary for Patent: 12,059,410