United States Drug Patent 9,487,491: Quizartinib Claims, Scope, Expiration, and Patent Landscape
US Patent No. 9,487,491 covers methods of treating cancer with quizartinib, also known as AC220. The patent claims treatment of non-small cell lung cancer, acute myelocytic leukemia, and atypical chronic myelocytic leukemia using quizartinib or a salt, including fumarate and hemifumarate forms. The patent is particularly relevant to FLT3-mutated acute myeloid leukemia, the approved use of quizartinib marketed as Vanflyta.
The patent does not claim quizartinib as a chemical compound generally. It claims therapeutic use. Its strongest commercial relevance is therefore a method-of-use barrier rather than a composition-of-matter barrier.
| Item |
Assessment |
| Patent |
US 9,487,491 B2 |
| Grant date |
November 8, 2016 |
| Active ingredient |
Quizartinib, also known as AC220 |
| Patent type |
Method of treatment |
| Core diseases |
NSCLC, AML, and atypical CML |
| Key biomarker |
FLT3 mutation, including FLT3-ITD |
| Dosage form |
Quizartinib or a salt; dependent claims specify fumarate and hemifumarate |
| Administration |
Oral administration in dependent claims |
| Claimed dose |
0.01 to 10 mg/kg/day |
| Patent-term endpoint |
August 21, 2027, subject to any applicable patent-term adjustment or extension |
| FDA product |
Vanflyta, quizartinib dihydrochloride |
| FDA approval |
July 20, 2023, for FLT3-ITD-positive newly diagnosed AML |
What drug and therapeutic use does US 9,487,491 cover?
The compound identified in the claims is quizartinib. It is a type II tyrosine kinase inhibitor with activity against FLT3, including FLT3 internal tandem duplication mutations. Daiichi Sankyo markets quizartinib dihydrochloride under the brand name Vanflyta.
The claims cover administering quizartinib to a patient for cancer treatment. The independent claims divide into two disease groups:
- Claim 1 covers treatment of non-small cell lung cancer.
- Claim 10 covers treatment of acute myelocytic leukemia or atypical chronic myelocytic leukemia.
The patent therefore extends beyond the current FDA-approved indication. Its NSCLC claims are especially important from a patent-scope perspective because claim 1 does not require a particular molecular biomarker, histology, treatment line, combination regimen, or disease stage.
How do the independent claims define infringement risk?
Claim 1: non-small cell lung cancer
Claim 1 requires:
- A patient in need of treatment;
- Administration of an effective amount;
- Quizartinib or a salt of quizartinib; and
- Treatment of non-small cell lung cancer.
The claim is broad in several respects. It does not limit:
- The salt form;
- The route of administration;
- The dose;
- The treatment line;
- Combination therapy;
- FLT3 mutation status; or
- A particular NSCLC subtype.
A product sponsor could face an infringement theory if it markets quizartinib for NSCLC, promotes that use, or induces another party to administer the product for NSCLC. The claim does not require that quizartinib be the only anticancer agent.
Claim 10: AML and atypical CML
Claim 10 covers treatment of:
- Acute myelocytic leukemia; or
- Atypical chronic myelocytic leukemia.
Like claim 1, claim 10 broadly covers quizartinib or a salt. It does not require a particular mutation, dose, formulation, route, or combination therapy.
The broad disease language makes claim 10 more commercially significant than the narrower biomarker claims. A generic sponsor could attempt to avoid claims directed to a specific FDA-approved population through labeling, but claim 10 creates a broader method-of-use issue because it recites AML without requiring FLT3-ITD status.
What do claims 11 and 12 add for FLT3-mutated leukemia?
Claim 11 narrows claim 10 to AML with specified FLT3 abnormalities:
- Mutant FLT3 polynucleotide-positive AML;
- FLT3 internal tandem duplication-positive AML; or
- AML with an FLT3 point mutation.
Claim 12 narrows claim 10 to atypical CML that is FLT3 fusion-polynucleotide positive.
These claims are technically narrower but commercially important. Vanflyta is approved for newly diagnosed FLT3-ITD-positive AML, placing the approved population within the subject matter of claim 11. The claim does not, however, recite the precise Vanflyta treatment regimen. It does not require induction chemotherapy, consolidation therapy, maintenance therapy, or a particular FLT3 diagnostic assay.
The absence of regimen limitations makes claim 11 potentially relevant to more than the exact FDA-approved combination regimen.
What protection do the fumarate and hemifumarate claims provide?
Claims 2 and 13 require a fumaric acid salt of quizartinib. Claims 3 and 14 specifically require quizartinib hemifumarate, identified in the patent as HFM.
The formulation hierarchy is:
| Claim group |
Salt limitation |
Disease |
| Claims 1, 4, 5, 10, 11, 12, 15, 16 |
Quizartinib or any salt |
NSCLC, AML, or atypical CML |
| Claims 2, 6, 7 |
Fumaric acid salt |
NSCLC |
| Claims 3, 8, 9 |
Hemifumarate |
NSCLC |
| Claims 13, 17, 18 |
Fumaric acid salt |
AML or atypical CML |
| Claims 14, 19, 20 |
Hemifumarate |
AML or atypical CML |
| Claims 21, 23, 24 |
Fumaric acid salt |
FLT3-mutated AML |
| Claims 22, 25, 26 |
Hemifumarate |
FLT3-mutated AML |
These salt-specific claims do not necessarily cover the marketed Vanflyta salt directly. Vanflyta is quizartinib dihydrochloride, while claims 2, 3, 13, 14, 21, and 22 focus on fumarate or hemifumarate. The broader "or a salt thereof" language in claims 1 and 10 is more relevant to the marketed dihydrochloride product.
The fumarate claims may still be relevant to development programs, clinical formulations, or alternative salt strategies. A competitor using a different salt could avoid the salt-specific claims while remaining exposed to the broader independent claims.
What do the oral-administration and dose claims protect?
Claims 4 through 9 and 15 through 26 add oral administration and, in most cases, a daily dose of 0.01 to 10 mg/kg.
The oral claims are narrower than claims 1 and 10. They may be useful against an oral product or oral clinical regimen, but they do not expand the underlying disease scope. The dose limitation is broad from a clinical perspective. It does not identify:
- A fixed milligram dose;
- Once-daily or twice-daily administration;
- A loading dose;
- A cycle length;
- A dose adjustment rule; or
- A maximum treatment duration.
A marketed oral product administered within the claimed weight-based range could fall within these dependent claims, but infringement analysis would require the actual labeled or promoted dose and the relevant claim construction.
What is the relationship between the patent claims and Vanflyta's FDA approval?
The FDA approved Vanflyta on July 20, 2023, for adult patients with newly diagnosed AML that is FLT3-ITD positive, in combination with cytarabine and anthracycline induction and cytarabine consolidation, followed by quizartinib maintenance as applicable under the approved regimen.[2]
The approved use maps most directly to claim 11 because it requires FLT3-ITD-positive AML. The product's dihydrochloride salt is covered by the broader "quizartinib or a salt thereof" language in claim 10 and potentially by claim 11 through its dependency on claim 10.
The FDA label does not convert every claim into an approved-use claim. The patent also covers unapproved NSCLC use and broader AML populations. FDA approval and patent scope must therefore be analyzed separately.
What is the Orange Book status of US 9,487,491?
US 9,487,491 is relevant to the Orange Book patent estate for quizartinib and Vanflyta as a method-of-use patent. The patent's practical significance depends on:
- Whether the patent is currently listed for the approved product;
- The use code assigned by the NDA holder;
- The relationship between the listed use code and the approved FLT3-ITD-positive AML indication; and
- Whether the listed patent remains enforceable after any terminal disclaimer, patent-term adjustment, or patent-term extension.
The patent's claimed AML subject matter is broader than the approved indication. A use code limited to FLT3-ITD-positive AML would narrow the Orange Book dispute compared with the full literal scope of claim 10.
For a generic applicant, the Orange Book listing determines whether an ANDA must include a Paragraph IV certification, a section viii statement, or a labeling carve-out. The patent claims alone do not determine the required certification.
When does US 9,487,491 lose exclusivity?
The patent's nominal expiration date is August 21, 2027. The effective date must be confirmed against the USPTO patent-term calculation and any applicable patent-term adjustment or extension.
The patent does not receive a new patent term merely because Vanflyta was approved in 2023. Patent-term extension under 35 U.S.C. ยง 156 is subject to statutory requirements, including regulatory review of an approved product and available extension periods. The Orange Book and USPTO records control the operative term.
Regulatory exclusivity is separate:
| Exclusivity type |
Relevant timing |
| Patent term |
Nominally through August 21, 2027 |
| New chemical entity exclusivity |
Generally five years from FDA approval, subject to statutory limitations |
| Orphan-drug exclusivity |
Potentially seven years for the approved orphan indication |
| FDA approval date |
July 20, 2023 |
The orphan exclusivity period is not a patent and does not block every possible generic or alternative indication. It generally prevents approval of the same drug for the same orphan indication unless a statutory exception applies. Patent expiration and regulatory exclusivity can therefore produce different entry dates.
Are there known Paragraph IV challenges to Vanflyta?
No publicly established Paragraph IV litigation against US 9,487,491 is identified in the supplied record. A complete current answer requires review of the latest Orange Book, FDA Paragraph IV litigation records, ANDA litigation filings, and PACER docket activity.
A Paragraph IV challenge would likely target one or more of the following:
- Anticipation or obviousness of the method claims;
- Written description or enablement;
- Lack of infringement based on a carved-out label;
- Noninfringement based on salt selection;
- Noninfringement based on the approved disease population;
- Invalidity based on prior clinical or patent disclosures; or
- Patent-term issues.
The patent's method-of-use structure creates a possible labeling strategy. A generic applicant could seek approval without the patented NSCLC use or without broader AML language, depending on the Orange Book use code and FDA labeling requirements. That strategy would not automatically eliminate induced-infringement risk if the generic sponsor promotes the patented use or the remaining label encourages it.
What generic entry risks exist after patent expiration?
Scenario 1: Full-label generic entry
A generic sponsor launches after patent and regulatory barriers expire with labeling for FLT3-ITD-positive AML. This is the highest substitution scenario because the generic would directly compete with Vanflyta in the approved indication.
Scenario 2: Carved-out labeling
A generic sponsor removes a patented use from its label under the section viii pathway. This strategy is viable only if the removed use is not required for the remaining label and the Orange Book use code can be meaningfully carved out.
Scenario 3: Alternative salt or formulation
A competitor develops a different quizartinib salt or formulation. The broad "salt thereof" claims in claims 10 and 11 could still create exposure if the product is used for the claimed diseases. The salt-specific claims would be easier to avoid than the broad method claims.
Scenario 4: Non-quizartinib FLT3 inhibitor
A competing FLT3 inhibitor does not infringe claims directed specifically to quizartinib. It may still compete commercially with Vanflyta and face its own composition, formulation, or method patents.
How strong is the patent estate for quizartinib?
US 9,487,491 has meaningful scope but is not a complete exclusivity platform by itself.
Strengths
- The independent AML claim is broad.
- Claim 11 aligns with the FLT3-ITD-positive AML population approved by FDA.
- The claims cover quizartinib and salts rather than only one salt form.
- The claims cover both AML and atypical CML.
- Oral and dose-dependent claims provide fallback positions.
Limitations
- The patent is a method-of-treatment patent, not a composition-of-matter patent.
- The nominal term ends in 2027, before the end of the likely orphan exclusivity period for the 2023 approval.
- Fumarate and hemifumarate claims do not directly correspond to the marketed dihydrochloride product.
- The claims do not recite the full approved Vanflyta regimen.
- Generic applicants may pursue labeling-based noninfringement strategies.
- Claim validity depends on prior art and the patent's disclosure of the disease and biomarker relationships.
The patent is strongest against a sponsor seeking to market quizartinib broadly for AML or FLT3-mutated AML before expiration. It is weaker as a standalone barrier against a carefully limited label, a non-quizartinib FLT3 inhibitor, or an alternative commercial strategy relying on regulatory exclusivity rather than patent protection.
Which companies compete with quizartinib?
The principal commercial comparator is midostaurin, marketed by Novartis as Rydapt, for newly diagnosed FLT3-mutated AML in combination with chemotherapy. Gilteritinib, marketed by Astellas as Xospata, is approved for relapsed or refractory FLT3-mutated AML. These products do not contain quizartinib and are not directly covered by US 9,487,491.
| Product |
Company |
FLT3-related AML position |
| Vanflyta, quizartinib |
Daiichi Sankyo |
Newly diagnosed FLT3-ITD-positive AML |
| Rydapt, midostaurin |
Novartis |
Newly diagnosed FLT3-mutated AML with chemotherapy |
| Xospata, gilteritinib |
Astellas |
Relapsed or refractory FLT3-mutated AML |
| Crenolanib |
Arog Pharmaceuticals and collaborators |
Investigational or development-stage FLT3 strategy |
| Sorafenib |
Bayer, generic manufacturers |
Off-label or combination use in selected AML settings |
A biosimilar pathway does not apply. Quizartinib is a small molecule, so competitive entry would occur through an ANDA, a 505(b)(2) application, or a new drug application rather than a biosimilar application.
What licensing and ownership issues affect the patent estate?
Quizartinib originated from Ambit Biosciences. Daiichi Sankyo acquired Ambit in 2014 for approximately $315 million upfront, with additional contingent value rights reported in the transaction materials.[5] The acquisition transferred control of Ambit's quizartinib program to Daiichi Sankyo.
The acquisition is more relevant than a conventional third-party license because it consolidated the development program, regulatory rights, and associated intellectual property under Daiichi Sankyo control. Any freedom-to-operate analysis should distinguish:
- Daiichi Sankyo's quizartinib patents;
- Earlier Ambit compound and formulation filings;
- Third-party FLT3 inhibitor patents;
- Manufacturing and crystalline-form patents; and
- Patent rights outside the United States.
Key Takeaways
- US 9,487,491 is a method-of-treatment patent covering quizartinib for NSCLC, AML, and atypical CML.
- Claim 10 is the principal broad AML claim.
- Claim 11 is commercially aligned with FLT3-ITD-positive AML, the core FDA-approved Vanflyta population.
- Claims 2, 3, 13, 14, 21, and 22 focus on fumarate or hemifumarate salts.
- The marketed product is quizartinib dihydrochloride, making the broader "salt thereof" claims more relevant than the hemifumarate claims.
- The nominal patent expiration date is August 21, 2027.
- FDA approval occurred on July 20, 2023, and regulatory exclusivity may extend beyond the patent term for the approved orphan indication.
- The patent is not a biosimilar issue because quizartinib is a small molecule.
- Generic entry could involve a Paragraph IV challenge, a section viii labeling carve-out, or delayed entry after patent and regulatory exclusivities.
- The strongest commercial risk is a generic or follow-on product seeking broad AML labeling before the patent expires.
FAQs About US 9,487,491 and Quizartinib
Does US 9,487,491 cover Vanflyta's dihydrochloride salt?
Potentially, through claims reciting quizartinib or a salt thereof. The patent's narrower fumarate and hemifumarate claims do not specifically cover dihydrochloride.
Does the patent cover all FLT3 inhibitors?
No. The claims identify the specific quizartinib molecular structure. Other FLT3 inhibitors, including midostaurin and gilteritinib, are not covered merely because they inhibit FLT3.
Can a generic launch quizartinib before August 2027?
A launch before patent expiration would face infringement risk unless the generic sponsor establishes invalidity, noninfringement, a permissible carved-out label, or another legally effective basis for entry.
Is the NSCLC use commercially important for Vanflyta?
Not for the current FDA-approved indication, which is FLT3-ITD-positive AML. It remains relevant because claim 1 creates a separate patent barrier against promoting or administering quizartinib for NSCLC.
Does orphan exclusivity prevent every quizartinib competitor?
No. Orphan exclusivity is indication-specific and does not create the same product-wide barrier as a composition-of-matter patent. It also does not block every alternative drug or every different indication.
References
-
U.S. Patent No. 9,487,491 B2. (2016). Methods for treating cancer using quizartinib. United States Patent and Trademark Office.
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U.S. Food and Drug Administration. (2023). Vanflyta (quizartinib) prescribing information. FDA.
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
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U.S. Food and Drug Administration. (2023). FDA approves quizartinib with chemotherapy for newly diagnosed acute myeloid leukemia. FDA.
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Daiichi Sankyo Co., Ltd. (2014). Daiichi Sankyo to acquire Ambit Biosciences. Daiichi Sankyo press release.
