United States Patent 12,023,325 (Ripretinib) Claims Scope, Effective Claim-Chart Coverage, and US Patent Estate Landscape
Executive summary: US Patent 12,023,325 claims a specific method-of-treatment for advanced gastrointestinal stromal tumor (GIST) using oral ripretinib at a 150 mg daily dose (once daily or twice daily), after prior imatinib, with a clinical performance limitation defined by mRECIST 1.1 progression-free survival (PFS) timing windows after 42-day dosing cycles. Dependent claims narrow the treated population to prior three or more kinase inhibitors (including imatinib; enumerated kinase inhibitor set) and/or 4+ lines of therapy, and narrow dosing to 150 mg once daily as three 50 mg tablets. A key practical point: the estate is likely to be litigated and designed around the enforceability of method performance limitations (mRECIST 1.1 PFS thresholds at defined timepoints) and around the dose schedule (150 mg; OD vs BID; tablet regimen) when assessing generic/authorized-competitor entry risk.
What does US Patent 12,023,325 claim protection for (ripretinib 150 mg method-of-use after imatinib)?
Core claim protected activity. Independent claim 1 is a method claim anchored on four requirement clusters:
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Indication and disease state
- “advanced gastrointestinal stromal tumor”
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Patient treatment history
- “previously been administered imatinib before administration of the ripretinib”
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Specific dosing
- “orally administering… a 150 mg once daily or twice daily dose of ripretinib”
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Objective clinical outcome limitation
- “treatment provides more than 3 months of progression free survival in patients as determined by mRECIST 1.1, after at least one cycle of 42 days of the daily ripretinib administration”
Practical enforceability focus. For litigation and freedom-to-operate, the “claim triggers” that matter most are not the drug alone, but the combination of:
- advanced GIST post-imatinib,
- the 150 mg/day regimen (OD or BID allowed),
- and the performance outcome measured with mRECIST 1.1 at timepoints tied to 42-day cycles.
How are “mRECIST 1.1” and the PFS timing limitation likely to be treated in claim scope?
This limitation is unusually outcome-anchored. In enforcement, plaintiffs typically rely on:
- clinical study endpoints or real-world evidence mapping to mRECIST 1.1,
- documentation that patients received at least the defined dosing exposure (at least one 42-day cycle for claim 1),
- statistical or patient-level assignment consistent with “more than 3 months” PFS.
For analysis of scope, the key interpretive question is what constitutes “provides” for method claims:
- whether “provides” requires the prescriber’s intent,
- or whether it is satisfied by the treatment’s demonstrated effect in the treated population.
This matters because the claim is drafted as if the method includes an efficacy guarantee.
Does the 150 mg OD vs BID language broaden the claim or limit it?
Claim 1 is written broadly on schedule:
- “once daily or twice daily dose”
- but narrow on daily total: 150 mg.
So any administration scheme that yields 150 mg/day and fits the OD or BID structure can fall within scope, even if administered as different tablet splits internally, unless limited by a dependent tablet-regimen claim (see claim 5).
How much additional protection do dependent claims add (3+ kinase inhibitors; 4+ lines; tablet regimen)?
Claim 2: 3 or more kinase inhibitors (including imatinib)
Claim 2 narrows to patients “previously administered three or more kinase inhibitors,” with imatinib included.
This creates:
- a population restriction (treatment history),
- but still leaves the dosing and outcome framework from claim 1 intact.
Scope implication: Even if an accused therapy uses ripretinib 150 mg/day post-imatinib, the claim 2 coverage adds an argument that the accused regimen must be applied in a patient population with 3+ prior kinase inhibitors including imatinib.
Claim 3: Enumerated inhibitor set
Claim 3 specifies a closed or quasi-closed set for the “three or more kinase inhibitors,” listing:
- imatinib, sunitinib, regorafenib, lapatinib, gefitinib, erlotinib, vatalanib, crenolanib
This narrows further by tying prior therapy to one of these named agents.
Scope implication: If a treated patient previously received a kinase inhibitor not in the list, claim 3 may not read cleanly onto that patient history, even if they had 3+ inhibitors overall.
Claim 4: 4 or more lines of therapy
Claim 4 adds a line-of-therapy threshold:
- “4 or more lines of therapy”
This is not coextensive with “3+ kinase inhibitors.” Many sequences can satisfy one but not the other depending on whether non-kinase therapies count as lines. Practically:
- claim 4 can capture broader sequencing scenarios than claim 3 if line-of-therapy includes modalities not enumerated as kinase inhibitors,
- but may still exclude some histories that meet kinase count but not line count.
Claim 5: 150 mg once daily as three 50 mg tablets
Claim 5 locks the dosing expression into a specific administration form:
- “150 mg a once daily dose”
- “three tablets each comprising 50 mg ripretinib”
This narrows to:
- once daily (not BID),
- and three 50 mg tablets per day.
Scope implication: Claim 5 is valuable if competitors or generics attempt to design dosing around different tablet strengths, different counting logic, or BID-only dosing. It also provides a clearer “product” hook: tablet count and strength.
Claim 6: Extended PFS at later timepoint
Claim 6 increases the performance bar:
- “more than 6 months progression free survival… after at least ten cycles of 42 days”
That implies:
- dosing exposure of at least 10 cycles × 42 days = 420 days (~14 months) before measuring the asserted outcome.
Scope implication: Claim 6 is narrower on efficacy and time. It may strengthen infringement arguments where real-world or study evidence shows longer PFS under the specified regimen and measurement method.
How does the claim language structure map into a litigation-ready claim chart?
A compact claim-chart skeleton (for analysis of coverage and design-around) is:
| Claim element |
What must be true |
| Disease |
Advanced GIST |
| Prior therapy |
Prior imatinib (claim 1) |
| Prior therapy count |
3+ kinase inhibitors with imatinib (claim 2) |
| Prior therapy identity |
prior inhibitors among enumerated list (claim 3) |
| Lines of therapy |
4+ lines (claim 4) |
| Drug |
ripretinib |
| Route |
oral administration |
| Dose |
150 mg/day, OD or BID (claim 1); OD only plus tablet regimen (claim 5) |
| Measurement method |
mRECIST 1.1 |
| Timepoint exposure |
at least one 42-day cycle (claim 1) |
| Efficacy outcome |
PFS > 3 months (claim 1); PFS > 6 months after 10 cycles (claim 6) |
This structure means noninfringement can attack any single element:
- dosing total,
- dosing schedule,
- oral administration compliance,
- patient eligibility history (imatinib only vs 3+ inhibitors; list restriction),
- or the endpoint methodology (mRECIST 1.1) and threshold.
When does US Patent 12,023,325 expire and how does exclusivity loss typically occur for ripretinib in GIST?
Executive answer: Expiration and any pediatric extension, PTA, or regulatory exclusivity interaction cannot be determined from the claim text alone. No patent metadata (filing date, earliest priority, grant date, PTA/adjustment, terminal disclaimer) is provided, so the exact US expiration date and exclusivity timing cannot be calculated from the inputs.
What can be concluded from the claim set: the claim is drafted to preserve enforceable control over specific clinical use in a defined post-imatinib advanced GIST population at 150 mg/day. Even after regulatory exclusivity ends, method claims can still impede generic entry if the generic label or off-label use overlaps the claimed method.
How many other US patents likely cover ripretinib methods in advanced GIST, and what are typical overlap patterns?
Executive answer: The number of other US patents cannot be quantified from claim text alone. A complete landscape requires the US patent family record, assignment, and Orange Book/FDA label linkage, none of which is supplied.
What the claim implies about likely overlap:
- Ripretinib’s US IP estate in GIST typically spans:
- dosing regimens (dose amount; OD/BID; tablet regimen),
- method-of-treatment endpoints with defined imaging/response criteria (mRECIST 1.1),
- patient selection features (post-imatinib; number of prior therapies),
- and sometimes combination or sequence-dependent claims.
Most likely overlap vectors for 12,023,325:
- dosing at 150 mg/day (device-tablet regimen in claim 5),
- post-imatinib sequencing,
- imaging-assessed PFS endpoints,
- and subpopulation selection by prior kinase inhibitor exposure.
What generic entry risks exist if a competitor launches an oral ripretinib 150 mg product (US method-of-use coverage)?
Risk profile depends on label and real-world practice
If a generic/competitor product is approved, the infringement risk from this patent would most likely arise via:
- prescribing for advanced GIST post-imatinib at 150 mg/day (OD or BID), and/or
- treating patients whose prior therapy history matches claim 2/3/4, and
- where efficacy outcomes measured by mRECIST 1.1 exceed claim thresholds after specified cycles.
Because the claims are method claims with outcome limitations, enforcement strategy often requires:
- clinical evidence demonstrating the claimed performance under the regimen,
- and patient-treatment traceability.
Design-around opportunities suggested by claim language
A competitor could attempt to reduce risk by:
- changing dose away from 150 mg/day (cannot be analyzed further without alternative dosing data),
- restricting to dosing schedules not covered (claim 5 OD constraint may not matter if claim 1 covers OD or BID),
- or shifting labeling to avoid method-coverage patient history (for claim 2/3/4).
However, claim 1’s OD or BID broadness makes simple OD vs BID switching insufficient.
What patent litigation affects US Patent 12,023,325 (Paragraph IV, IPR, district court cases)?
Executive answer: Litigation status, IPR challenges, and any Paragraph IV certifications tied to US Patent 12,023,325 cannot be determined from the provided inputs. No lawsuit captions, parties, dockets, or FDA listing/certification details are included.
What is the Orange Book status of US Patent 12,023,325 (listed drug, FDA approval link)?
Executive answer: Orange Book listing status cannot be determined from the claim text alone. No drug NDA/BLA number, Orange Book patent list, or “listed” patent association is provided.
How does US Patent 12,023,325 compare with other ripretinib patent claim strategies (dose-only vs endpoint vs patient-history)?
Executive answer: A comparison requires access to the other patent claims in the ripretinib family. Not provided.
However, based on the claim drafting style, US 12,023,325 belongs to the “endpoint-and-selection” subgroup, using:
- post-imatinib selection,
- prior therapy count and identity constraints (claims 2-4),
- dosing schedule and tablet regimen constraint (claims 1 and 5),
- imaging endpoint methodology (mRECIST 1.1),
- time-exposure constraints tied to 42-day cycles,
- and outcome thresholds (PFS > 3 months; > 6 months).
This differs from patents that only claim a composition, a manufacturing process, or a dosing amount without efficacy/time constraints.
Where are the most vulnerable claim points for enforcement or validity challenges?
Without case citations, the assessment is limited to claim-structure vulnerabilities:
Outcome limitation and measurement-method dependence
- The requirement that PFS is “as determined by mRECIST 1.1” ties infringement to a specific imaging/response framework. If the outcome in an accused regimen is generated under different imaging rules, that can be a noninfringement pathway.
- The “more than 3 months” and “more than 6 months” thresholds require mapping of measurement and analysis methodology.
Patient-history constraints
- Claim 2 depends on “three or more kinase inhibitors” including imatinib.
- Claim 3 depends on a named set of inhibitors.
- Claim 4 depends on “4 or more lines of therapy.”
These make infringement more fact-dependent than broad “advanced GIST after imatinib” methods that do not further constrain history.
Dose schedule and tablet regimen
- Claim 5 is narrow (three 50 mg tablets once daily).
- Claim 1 is broader on OD/BID but fixed on total daily dose of 150 mg.
Key Takeaways
- US 12,023,325 is a method-of-treatment patent centered on oral ripretinib 150 mg/day for advanced GIST after imatinib, with infringement dependent on mRECIST 1.1 PFS thresholds tied to 42-day dosing cycles.
- Dependent claims narrow patient history to 3+ prior kinase inhibitors (imatinib included; named inhibitor set in claim 3) and/or 4+ lines of therapy.
- Dependent claim 5 adds a product-adjacent dosing structure: 150 mg once daily as three 50 mg tablets.
- Dependent claim 6 tightens efficacy and duration: PFS > 6 months after 10 cycles (42 days each).
- Enforceability and design-around risk hinge on (i) patient eligibility history, (ii) dosing total and schedule, and (iii) how PFS is measured (mRECIST 1.1) and at what analyzed timepoint.
- Patent expiration, Orange Book status, and litigation/Paragraph IV exposure cannot be determined from the information provided.
FAQs
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Does US 12,023,325 cover both once-daily and twice-daily ripretinib dosing?
Claim 1 covers 150 mg/day given as “once daily or twice daily.” Claim 5 covers “once daily” specifically with a three-tablet regimen.
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What prior therapies are required for infringement under claims 2 and 3?
Claim 2 requires 3+ prior kinase inhibitors including imatinib. Claim 3 restricts the prior kinase inhibitors to the listed agents.
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Does the patent require the clinician to use mRECIST 1.1 to assess PFS?
The claim uses “PFS… as determined by mRECIST 1.1,” making the measurement framework a central element of the claimed method.
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How is the timepoint for PFS measured in claim 1 and claim 6?
Claim 1 looks to after at least one 42-day cycle with PFS “more than 3 months.” Claim 6 looks after at least ten 42-day cycles with PFS “more than 6 months.”
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Can a competitor avoid infringement by changing the dosing schedule but keeping the same total daily dose?
Claim 1 allows OD or BID at 150 mg/day, so schedule changes alone do not avoid scope unless the regimen diverges from the claim’s dosing structure or the dependent tablet regimen in claim 5.
References (APA)
- Provided claim text for US Patent 12,023,325 (user-supplied).
