Details for Patent: 11,103,497

Which drugs does patent 11,103,497 protect, and when does it expire?

Patent 11,103,497 protects BOSULIF and is included in two NDAs.

Protection for BOSULIF has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has thirty-eight patent family members in twenty-two countries.

Summary for Patent: 11,103,497

Title:	Treatment of imatinib resistant leukemia
Abstract:	The present invention provides 4-anilino-3-quinolinecarbonitriles compounds useful for treating a subject having an BcrAbl positive leukemia that is resistant to imatinib.
Inventor(s):	Becker Hewes
Assignee:	Wyeth LLC
Application Number:	US12/129,935
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,103,497
Patent Claim Types: see list of patent claims	Use;

US Patent 11,103,497: Bosutinib Patent Scope, Claim Analysis, Expiration, and Generic Entry Risk

US Patent 11,103,497 protects a mutation-specific method of using bosutinib to treat imatinib-resistant BCR-ABL-positive leukemia. Its independent claims are limited to patients with either the BCR-ABL F317L protein mutation or the corresponding 949T>C nucleic-acid mutation. The patent does not broadly claim bosutinib, all BCR-ABL mutations, or all imatinib-resistant leukemia patients.

The patent is part of the broader Bosulif patent estate associated with Pfizer and Wyeth. Its commercial significance depends on whether a generic applicant seeks approval for a label covering F317L-positive disease, CML or ALL treatment, or combination treatment with imatinib.

What drug does US Patent 11,103,497 protect?

The compound recited in each independent claim is bosutinib, marketed by Pfizer as Bosulif.

Characteristic	Data
Active ingredient	Bosutinib
Chemical name in patent claims	4-[(2,4-Dichloro-5-methoxy-phenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile
Product	Bosulif
Molecular target	BCR-ABL tyrosine kinase, with activity against SRC-family kinases
FDA sponsor	Pfizer
Main indications	Philadelphia chromosome-positive chronic myelogenous leukemia and related BCR-ABL-positive leukemia settings
Dosage form	Oral tablets
FDA approval	2012 initial approval; later label expansions
Patent type	Method-of-treatment patent

Bosutinib is a second-generation BCR-ABL tyrosine-kinase inhibitor. The patent focuses on use against leukemia associated with the F317L resistance mutation, a mutation known to affect sensitivity to several earlier BCR-ABL inhibitors.

What are the independent claims in US Patent 11,103,497?

Claims 1 and 2 are the independent claims.

Claim 1: F317L protein mutation

Claim 1 requires all of the following:

1. A subject has BCR-ABL-positive leukemia.
2. The leukemia is resistant to imatinib.
3. The subject has an F317L mutation in the BCR-ABL protein.
4. The subject receives a therapeutically effective amount of bosutinib.

This is a patient-selection claim. The claim is not satisfied merely because bosutinib is administered to a patient with CML. The patient must have the specified mutation and imatinib-resistant disease.

Claim 2: 949T>C nucleic-acid mutation

Claim 2 covers the corresponding genetic mutation at nucleotide position 949:

1. BCR-ABL-positive leukemia;
2. imatinib resistance;
3. a resistance-associated BCR-ABL gene mutation at 949T>C; and
4. administration of a therapeutically effective amount of bosutinib.

The protein and nucleic-acid claims are alternative routes to substantially the same clinical population. Claim 1 identifies the mutation at the protein level. Claim 2 identifies it at the gene-sequence level.

How do the dependent claims narrow the patent scope?

Claims 3 through 10 narrow the independent claims by disease type and treatment combination.

Claim	Limitation
3	Claim 1 patient has chronic myelogenous leukemia
4	Claim 2 patient has chronic myelogenous leukemia
5	Claim 1 patient has acute lymphocytic leukemia
6	Claim 2 patient has acute lymphocytic leukemia
7	Claim 1 treatment is combined with another BCR-ABL leukemia therapy
8	Claim 2 treatment is combined with another BCR-ABL leukemia therapy
9	Claim 7 combination includes imatinib
10	Claim 8 combination includes imatinib

Claims 3 and 4 are particularly relevant to the commercial Bosulif label because CML is the principal approved disease setting. Claims 5 and 6 extend the coverage to acute lymphocytic leukemia, but their practical value depends on the FDA-approved label and actual clinical use.

Claims 7 through 10 create combination-treatment coverage. Claims 9 and 10 are unusual in that they expressly include imatinib even though the treated subject must be resistant to imatinib. The claim language permits sequential or concurrent combination treatment, but infringement analysis would depend on the treatment protocol, physician instructions, and the applicable construction of “in combination.”

What patient population is covered by US Patent 11,103,497?

The core population is:

• BCR-ABL-positive leukemia;
• resistance to imatinib;
• F317L or 949T>C mutation; and
• treatment with bosutinib.

The claims do not expressly require:

• a particular bosutinib dose;
• a particular treatment duration;
• a particular tablet strength;
• a specific line of therapy beyond imatinib resistance;
• a specific level of BCR-ABL transcript reduction;
• a particular laboratory assay;
• prior treatment with dasatinib or nilotinib; or
• a specific disease stage.

The claims therefore cover the administration method broadly once the required patient characteristics are present.

The mutation requirement materially limits the claims. A patient with another imatinib-resistance mutation, such as T315I, E255K, Y253H, or M351T, is outside claims 1 and 2 unless the patient also has the claimed F317L or 949T>C alteration.

What is the relationship between F317L and 949T>C?

F317L is the amino-acid substitution. The 949T>C mutation identifies the corresponding nucleotide change in the BCR-ABL coding sequence, depending on the reference sequence used.

The two claims are drafted as separate independent claims because mutation nomenclature can be determined through different clinical tests:

• sequencing of the BCR-ABL gene can identify 949T>C;
• protein-level or translated-sequence reporting can identify F317L.

A generic applicant could face different infringement positions depending on whether its proposed label recommends treatment for “F317L-positive” patients, “949T>C-positive” patients, or imatinib-resistant patients without expressly naming the mutation.

What is the patent term and expiration date?

US Patent 11,103,497 was granted on October 19, 2021. Public patent records identify the patent as part of the bosutinib/BCR-ABL treatment family with an original priority chain dating to the mid-2000s. On a standard 20-year patent-term calculation, the family is expected to expire in 2027, subject to patent-term adjustment, terminal disclaimers, and any applicable regulatory patent-term extension.

Event	Date or period
Earliest family priority	2006-era priority date publicly associated with the BCR-ABL/bosutinib family
US patent grant	October 19, 2021
Expected base term	2027-era expiration
Potential adjustment	Patent-term adjustment may alter the expiration date
Regulatory exclusivity	Separate from patent term and dependent on FDA exclusivity records

The legally operative expiration date should be determined from the USPTO patent record and the Orange Book entry for the specific patent. A grant date does not restart the patent term.

What patents protect Bosulif and bosutinib?

Bosutinib has a layered patent estate rather than a single patent.

Composition-of-matter protection

The original composition patents protect bosutinib or closely defined chemical classes containing the bosutinib structure. These patents are generally more important to generic entry than a mutation-specific method patent because they can block manufacture, sale, and use of the active ingredient across indications.

Method-of-treatment patents

US Patent 11,103,497 covers bosutinib treatment for the defined imatinib-resistant, F317L or 949T>C-positive population. Other family members may cover broader BCR-ABL leukemia treatment, specific mutation profiles, or particular treatment settings.

Formulation and dosage-form patents

Bosulif is sold as an oral tablet. Formulation protection may cover:

• tablet composition;
• excipient combinations;
• dissolution characteristics;
• dosage strengths;
• solid-state or salt forms; and
• manufacturing processes.

A formulation patent must be analyzed separately from US Patent 11,103,497 because the asserted claims provided here do not recite a tablet, excipient, crystalline form, particle-size range, or release profile.

Manufacturing and process protection

Process patents may protect preparation of bosutinib, intermediates, purification methods, or solid forms. These patents can create manufacturing barriers even when a generic applicant avoids an expired composition patent.

What is the Orange Book status of US Patent 11,103,497?

Orange Book listing is important because a listed patent can require an ANDA applicant to make a Paragraph IV certification or submit a section viii statement, depending on the patent claims and the proposed labeling.

A method-of-use patent like US 11,103,497 may be listed against Bosulif if the patent claims an FDA-approved use. If the approved labeling includes treatment of imatinib-resistant, BCR-ABL-positive leukemia involving the covered mutation, the patent may create a use-code issue.

Orange Book issue	Relevance
Patent listed against Bosulif	Determines whether an ANDA applicant must address the patent
Use code	Defines the approved method allegedly covered
Paragraph IV certification	Challenges patent validity, enforceability, or infringement
Section viii statement	Carves out a patented method from the proposed label
30-month stay	May apply if the NDA holder or patent owner files timely suit
Label carve-out	May reduce infringement exposure but must remove the patented use

An Orange Book entry does not itself establish patent validity or infringement. The entry identifies a patent and the approved use allegedly covered.

Could a generic bosutinib applicant avoid this patent?

Yes. The principal design-around is a label that omits the patented mutation-specific use.

Section viii strategy

A generic applicant may seek approval for non-patented bosutinib uses while carving out treatment of:

• F317L-positive leukemia;
• 949T>C-positive leukemia;
• imatinib-resistant patients with those mutations; or
• combination use with imatinib, if the relevant use is separately listed.

This approach is viable only if the remaining label does not induce or directly encourage the patented use. FDA labeling rules and the final use code are central.

Paragraph IV challenge

An applicant may instead certify that the patent is:

• invalid;
• unenforceable; or
• not infringed.

A Paragraph IV certification can trigger patent litigation if the patent owner files suit within the statutory period. The principal potential defenses would include lack of written description, enablement, anticipation, obviousness, indefiniteness, and non-infringement.

ANDA manufacturing does not avoid all patent risk

Even if a generic label excludes the F317L indication, the applicant must separately evaluate composition, formulation, salt, polymorph, process, and other method patents. Avoiding US Patent 11,103,497 does not establish freedom to operate for bosutinib generally.

Which companies are challenging Bosulif exclusivity?

The relevant competitive group includes:

• generic drug manufacturers pursuing bosutinib ANDAs;
• Pfizer as NDA holder and patent owner or licensee;
• contract manufacturers and API suppliers;
• potential applicants using section viii labeling carve-outs; and
• suppliers challenging composition, formulation, or method patents.

A definitive list of Paragraph IV challengers requires current FDA Orange Book, FDA Paragraph IV litigation, and federal court docket data. The supplied claim text does not establish that a particular company has filed a Paragraph IV certification or litigation against US Patent 11,103,497.

What patent litigation affects US Patent 11,103,497?

The patent number alone does not establish an active infringement case. Patent litigation must be confirmed through PACER, district-court docket records, FDA Paragraph IV notices, and the Orange Book patent listing.

For commercial diligence, the relevant litigation questions are:

1. Has an ANDA applicant certified Paragraph IV against the patent?
2. Did Pfizer or another patent owner file suit within the statutory period?
3. Is there a 30-month stay?
4. Does the case involve the mutation-specific use code or a different Bosulif patent?
5. Has the case ended through dismissal, judgment, settlement, or covenant not to sue?
6. Does any settlement permit an agreed generic launch date?

A settlement involving another Bosulif patent may not resolve US Patent 11,103,497 unless the agreement expressly covers it.

How strong is the patent estate for bosutinib?

Strengths

The patent has several claim-construction advantages:

• The compound is precisely identified.
• The F317L and 949T>C limitations are technically specific.
• The claims target a clinically recognized resistance population.
• The claims do not include a narrow dose or formulation limitation.
• Dependent claims create separate CML, ALL, and combination-treatment positions.

Vulnerabilities

The principal vulnerabilities are:

• narrow patient-population coverage;
• possible enablement and written-description challenges if the specification does not adequately support the claimed mutation-specific treatment;
• obviousness arguments based on prior knowledge of bosutinib activity against BCR-ABL mutants;
• potential difficulty proving that a generic label induces treatment of the claimed mutation;
• possible inability to enforce the claim where the mutation is not tested or documented; and
• possible expiration before broad commercial exclusivity can be maintained.

The patent is stronger against an expressly mutation-directed label than against a broad, non-mutation-specific bosutinib label that omits the patented use.

What is the likely generic launch impact?

The commercial impact depends on whether bosutinib composition and formulation patents remain enforceable when US Patent 11,103,497 expires.

Launch scenario	Effect
Generic label includes F317L or 949T>C use	Higher risk of infringement litigation
Generic label excludes mutation-specific use	Potential section viii pathway
Composition patent remains in force	Patent may block launch despite method carve-out
Only method patents remain	Earlier partial or full launch may be possible
Settlement permits licensed entry	Entry date depends on agreement terms
Bosulif label retains covered use	Method patent may remain commercially relevant
Covered use is rarely prescribed	Lower practical exposure even if legally enforceable

Because claims 1 and 2 are use-specific, the patent is unlikely by itself to block every bosutinib generic. The broader commercial barrier is the combined patent estate, including composition, formulation, process, and other method patents.

How does US Patent 11,103,497 compare with competing BCR-ABL inhibitor patents?

Drug	Commercial position	Typical patent issue
Bosutinib	Second-generation BCR-ABL inhibitor	Composition, formulation, and mutation-specific methods
Imatinib	First-generation BCR-ABL inhibitor	Historic composition and use protection largely expired
Dasatinib	Second-generation BCR-ABL/SRC inhibitor	Composition, dosing, formulation, and resistance-mutation claims
Nilotinib	Second-generation BCR-ABL inhibitor	Composition, dosing, and formulation protection
Ponatinib	Later-generation inhibitor with T315I activity	Composition, dosing, safety, and patient-selection patents
Asciminib	Allosteric BCR-ABL inhibitor	Composition, formulation, combination, and treatment-line patents

F317L is relevant to comparative inhibitor selection because resistance profiles differ across BCR-ABL drugs. A patent claim directed to F317L-positive disease may have greater strategic value than a generic leukemia-use claim if the mutation materially affects treatment choice.

Does US Patent 11,103,497 cover biosimilars?

No. Bosutinib is a chemically synthesized small molecule, not a biologic. Biosimilar provisions under the Biologics Price Competition and Innovation Act do not apply.

The relevant competitor pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act. Generic applicants must address listed patents through Paragraph IV certifications, section viii statements, or other applicable certifications.

Key Takeaways

• US Patent 11,103,497 covers bosutinib treatment of imatinib-resistant BCR-ABL-positive leukemia.
• The independent claims require either F317L or the corresponding 949T>C mutation.
• Claims 3 through 6 narrow the disease to CML or ALL.
• Claims 7 through 10 cover combination treatment, including combinations with imatinib.
• The patent does not broadly cover bosutinib composition, all BCR-ABL mutations, or every imatinib-resistant leukemia patient.
• The patent is expected to expire in the 2027-era term, subject to the official USPTO term calculation.
• Generic exposure depends on the combined Bosulif patent estate, not this patent alone.
• A section viii carve-out may reduce risk if a generic label omits the F317L and 949T>C uses.
• A Paragraph IV challenge could attack validity, enforceability, or infringement.
• The patent has greater practical force against an expressly mutation-directed label than against a non-specific bosutinib label.

FAQs

Does US Patent 11,103,497 cover bosutinib for T315I-mutated leukemia?

No. The supplied claims specifically require F317L or 949T>C. T315I is a different BCR-ABL mutation and is outside the literal scope of these claims.

Does the patent cover bosutinib for newly diagnosed CML?

Not based on the supplied claim language alone. The claims require that the subject be resistant to imatinib. A newly diagnosed patient with no imatinib-resistance history would generally fall outside the claims.

Can a generic label mention imatinib-resistant leukemia without naming F317L?

Potentially, but the risk depends on the final label, use code, prescribing instructions, and whether the labeling encourages treatment of the claimed mutation-defined population.

Does combining bosutinib with imatinib create separate patent risk?

Yes. Claims 9 and 10 expressly recite bosutinib treatment combined with imatinib. A label or promotional strategy directing that combination could create additional infringement exposure.

Is US Patent 11,103,497 the main patent blocking generic Bosulif?

Not necessarily. Composition, formulation, process, and broader method patents may present a more substantial barrier. A complete freedom-to-operate analysis must evaluate the entire Bosulif patent and regulatory exclusivity record.

References

1. U.S. Patent and Trademark Office. (2021). U.S. Patent No. 11,103,497, methods of treating BCR-ABL-positive leukemia. https://patents.google.com/patent/US11103497

2. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/

3. U.S. Food and Drug Administration. (2024). Bosulif (bosutinib) prescribing information. Pfizer. https://www.accessdata.fda.gov/drugsatfda_docs/label/

4. U.S. Food and Drug Administration. (2012). FDA approves Bosulif to treat chronic myelogenous leukemia. https://www.fda.gov/

5. U.S. Food and Drug Administration. (2024). Generic drugs and patent certifications under the ANDA pathway. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda

Drugs Protected by US Patent 11,103,497

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pf Prism Cv	BOSULIF	bosutinib monohydrate	CAPSULE;ORAL	217729-001	Sep 26, 2023		RX	Yes	No					Y
Pf Prism Cv	BOSULIF	bosutinib monohydrate	CAPSULE;ORAL	217729-002	Sep 26, 2023		RX	Yes	Yes					Y
Pf Prism Cv	BOSULIF	bosutinib monohydrate	TABLET;ORAL	203341-001	Sep 4, 2012	AB	RX	Yes	Yes					Y
Pf Prism Cv	BOSULIF	bosutinib monohydrate	TABLET;ORAL	203341-003	Oct 27, 2017	AB	RX	Yes	No					Y
Pf Prism Cv	BOSULIF	bosutinib monohydrate	TABLET;ORAL	203341-002	Sep 4, 2012	AB	RX	Yes	No					Y

International Family Members for US Patent 11,103,497

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2008260070
Brazil	PI0812355
Canada	2688467
Canada	2868899
Canada	2964162
Chile	2008001577
China	101686973