Details for Patent: 11,192,897

Which drugs does patent 11,192,897 protect, and when does it expire?

Patent 11,192,897 protects ICLUSIG and is included in one NDA.

This patent has thirty-seven patent family members in nine countries.

Summary for Patent: 11,192,897

Title:	Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt
Abstract:	Novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide free base and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, pharmaceutical compositions thereof and methods of their preparation and use are disclosed herein.
Inventor(s):	Christopher K. Murray, Leonard W. Rozamus, John J. Chaber, Pradeep K. Sharma
Assignee:	Takeda Pharmaceuticals USA Inc
Application Number:	US17/318,832
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,192,897
Patent Claim Types: see list of patent claims	Use; Composition;

US 11,192,897 protects defined crystalline forms of ponatinib hydrochloride, stability-qualified material, mixtures containing Form A, and selected leukemia treatment methods. Its strongest commercial coverage is the solid form itself. The treatment claims are narrower and depend on proving that the administered ponatinib hydrochloride is the claimed crystalline form or that the composition contains at least two crystalline forms.

US Patent 11,192,897: Ponatinib Hydrochloride Crystalline Form Patent Analysis

What does US 11,192,897 protect?

US 11,192,897 protects crystalline ponatinib hydrochloride identified through four principal claim strategies:

1. X-ray powder diffraction, or XRPD, peak positions.
2. Stability and humidity-resistance characteristics.
3. Thermal behavior, including melting temperature.
4. Pharmaceutical compositions and leukemia treatment methods.

Ponatinib is the active ingredient in Iclusig, marketed by Takeda Pharmaceuticals for Philadelphia chromosome-positive chronic myeloid leukemia, or Ph+ CML, and Philadelphia chromosome-positive acute lymphoblastic leukemia, or Ph+ ALL. The patent does not claim ponatinib as a chemical entity generally. It targets a solid-state form of ponatinib hydrochloride and uses of that form. (U.S. Patent No. 11,192,897)

The patent therefore sits in the solid-form and formulation layer of the ponatinib patent estate rather than at the foundational active-pharmaceutical-ingredient level.

How broad are the XRPD claims in US 11,192,897?

Claims 1 through 4 define the crystalline form by selected XRPD peaks. The listed values are measured in 2θ degrees with a tolerance of ±0.3 degrees.

Claim	Minimum number of listed XRPD values	Peak pool	Practical scope
1	3	22 listed peaks	Broadest diffraction-defined claim
2	4	Same 22 peaks	Narrower subgenus
3	5	Same 22 peaks	Narrower still
4	3	13 listed peaks	Alternative restricted peak set

Claim 1 covers a crystalline ponatinib hydrochloride form whose XRPD pattern includes at least three values selected from the listed peak positions. It does not require all 22 peaks. It also does not expressly require a particular relative intensity, peak order, lattice parameter, solvent content, water content, or full XRPD fingerprint.

That drafting approach creates both breadth and enforcement complexity. A generic manufacturer could argue that three coincident peaks are insufficient to establish identity with the patented form, particularly where several crystalline forms or polymorphs share common reflections. The patent holder would likely rely on the specification, full-pattern comparison, additional characterization data, and claim-construction evidence to establish that the claimed peaks identify the relevant form.

Claim 4 uses a shorter 13-peak set. It may be valuable if the full peak list is not consistently observed because of instrument configuration, sample preparation, particle size, preferred orientation, or crystallinity differences.

What is the significance of the ±0.3-degree tolerance?

The ±0.3-degree tolerance increases the practical capture range around each listed peak. It also creates an infringement question around analytical methodology. XRPD peak positions can vary with:

• Instrument calibration.
• Radiation source.
• Sample preparation.
• Temperature and humidity.
• Grinding and particle-size distribution.
• Preferred orientation.
• Amorphous content.
• Hydration or solvation state.

An accused product would ordinarily require testing under controlled conditions. A single peak outside the tolerance would not necessarily avoid infringement if other required peaks fall within the claimed range. Conversely, three coincidental peaks may not establish infringement if the overall solid form is materially different.

What do the stability claims cover?

Claim 5 defines a crystalline form through resistance to physical or chemical change under specified stress conditions. The claim uses “and/or,” allowing coverage when one or more of the listed stability conditions are satisfied.

The conditions are:

Stability test	Claimed condition
Heat stability	No XRPD change and no apparent HPLC degradation after up to 72 hours at 70°C
High-temperature exposure	No XRPD change and no apparent HPLC degradation after 5 minutes at 220°C
Dynamic vapor sorption	No XRPD change and unchanged DVS isotherm after 0-95-0% relative-humidity cycling followed by 0-45% cycling
Humidity exposure	No XRPD and DSC change after six days at 75% relative humidity

Claims 6 through 10 add testing details:

• HPLC uses UV detection at 260 nm.
• “No apparent degradation” means at least 99% area/area for the ponatinib peak.
• The 70°C test can occur under dry nitrogen.
• DVS analysis occurs at 25°C.
• The 75% relative-humidity test occurs at 40°C.

These claims are product claims, not merely process claims. A commercial batch could infringe without being manufactured by the disclosed process if it possesses the claimed stability characteristics.

The principal limitation is evidentiary. The claim requires defined analytical outcomes, but the meaning of “does not change,” “no apparent degradation,” and “DVS isotherm does not change” may depend on the specification’s test methods, acceptance criteria, and examples. The 99% HPLC threshold in claim 7 is more objective than the broader language in claim 5.

What does the melting-point coverage add?

Claims 11 and 12 cover a crystalline ponatinib hydrochloride form with an onset melting temperature of 262°C to 264°C. Claim 12 narrows the form to a peak melting temperature of 264°C.

Claim	Thermal limitation
11	Onset melting temperature of 262°C to 264°C
12	Peak melting temperature of 264°C

Thermal analysis can distinguish forms, but melting temperature is sensitive to:

• Heating rate.
• Instrument calibration.
• Sample mass.
• Pan type.
• Atmospheric conditions.
• Purity.
• Decomposition before or during melting.
• Definition of onset and peak.

Claims 11 and 12 may provide an alternative infringement route where XRPD results are inconclusive. They also create design-around possibilities if a competing form has a melting onset or peak outside the claimed range while retaining comparable pharmaceutical performance.

What compositions are protected by claims 13 and 14?

Claim 13 covers a pharmaceutical composition comprising:

1. At least two crystalline forms of ponatinib hydrochloride; and
2. A pharmaceutically acceptable carrier.

Claim 14 requires that one of those forms is Form A.

The claim does not state a minimum ratio between the forms, a specific carrier, a dosage strength, a tablet architecture, or a release profile. On its face, a composition containing two crystalline forms in a small or unspecified proportion could fall within the claim, provided both forms are present and the carrier is pharmaceutically acceptable.

The weakness is identification. “Form A” must be defined by the patent specification or incorporated technical disclosure. A formulation containing two forms may be difficult to characterize after tableting, granulation, compression, coating, or storage. The patent holder would likely need batch-level XRPD, DSC, microscopy, spectroscopy, or solid-state NMR data.

What formulation patents are relevant to ponatinib?

US 11,192,897 is not a conventional excipient or delivery-system patent. It does not expressly require:

• A particular tablet composition.
• A specific dissolution profile.
• A coating material.
• A dosage strength.
• A controlled-release mechanism.
• A particle-size range.
• A manufacturing sequence.

Its formulation relevance comes from the requirement that the composition contain at least two crystalline ponatinib hydrochloride forms. This is narrower than a broad tablet-composition patent but potentially broader than a process-specific claim.

What treatment methods are protected?

Claims 15 through 23 cover treatment methods using the claimed crystalline form or the composition containing at least two crystalline forms.

CML claims

Claim 15 covers treatment of CML. The dependent claims identify:

• Chronic phase CML.
• Acute phase CML.
• Blast phase CML.
• Resistance or intolerance to at least one prior tyrosine-kinase inhibitor.
• Resistance or intolerance to at least two prior tyrosine-kinase inhibitors.
• Disease associated with a BCR-ABL kinase-domain mutation.

Claims 16 through 21 therefore target clinically defined populations with substantial overlap with ponatinib’s labeled use. The mutation limitation in claim 21 is particularly relevant because ponatinib is used in patients with resistant BCR-ABL disease, including T315I-mutated disease.

Ph+ ALL claims

Claim 22 covers treatment of Ph+ ALL. Claim 23 narrows the method to leukemia resulting from a BCR-ABL kinase-domain mutation.

The method claims require administration of either:

• The crystalline form covered by claim 1; or
• The pharmaceutical composition covered by claim 13.

This is important. A generic product containing ponatinib hydrochloride in a different solid form may avoid the method claims if the administered material does not meet the claim 1 XRPD limitations and the product is not a composition containing at least two claimed forms.

Are claims 17 and 18 internally inconsistent?

Claims 17 and 18 are drafted as dependent on claim 16, while claim 16 recites chronic-phase CML. Claim 17 then recites acute-phase CML, and claim 18 recites blast-phase CML.

Under ordinary claim-dependency rules, a dependent claim incorporates all limitations of the claim from which it depends. That creates a formal inconsistency: claims 17 and 18 appear to retain the chronic-phase limitation while adding acute-phase or blast-phase language.

A court could construe the claims in light of the specification and prosecution history, or treat the dependency as an obvious drafting error if correction is legally available. A generic challenger could raise indefiniteness, lack of clarity, or written-description arguments. The defect does not necessarily invalidate the broader claim 15 or the correctly dependent claims, but it reduces the reliability of claims 17 and 18 as independent litigation assets.

When does US 11,192,897 lose exclusivity?

The patent’s exact expiration date cannot be determined from the claims alone. It depends on the patent’s earliest effective nonprovisional priority date, patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.

The relevant calculation is:

Term component	Relevance
Earliest effective U.S. nonprovisional filing date	Establishes the basic 20-year term
Patent-term adjustment	Can extend the term for USPTO delay
Terminal disclaimer	Can limit expiration to another patent’s expiration date
Patent-term extension	May apply only if statutory requirements are met
Pediatric exclusivity	Can add six months to qualifying FDA exclusivity periods, not automatically to every patent

The patent should therefore be evaluated through the USPTO Patent Center record, the front-page term data, and the FDA Orange Book patent listing. FDA regulations require listed patents to be evaluated in connection with approved drug products and generic certification procedures. (FDA, 2024a; 21 U.S.C. § 355)

What is the Orange Book status of US 11,192,897?

Orange Book treatment depends on whether the patent is listed against the approved Iclusig drug product and whether FDA accepted the patent as covering the drug substance, drug product, or approved method of use.

The patent has three possible Orange Book relevance categories:

Category	Relevance to US 11,192,897
Drug substance	Possible if FDA accepted the crystalline ponatinib hydrochloride form as covering the active ingredient
Drug product	Possible through the composition claims involving multiple crystalline forms
Method of use	Possible for CML or Ph+ ALL indications covered by the approved labeling

An Orange Book listing is commercially important because an ANDA applicant may be required to certify under Paragraph I, II, III, or IV. A Paragraph IV certification alleges that the listed patent is invalid, unenforceable, or not infringed. The patent’s presence in the Orange Book would not by itself establish that every generic ponatinib product infringes. The listed claim category and the generic’s proposed product must be compared claim by claim. (FDA, 2024a)

Which companies could challenge the patent?

The most likely challengers are:

• ANDA applicants seeking generic ponatinib tablets.
• Contract manufacturers supplying generic ponatinib.
• Applicants using an alternative ponatinib polymorph, amorphous form, hydrate, solvate, or salt.
• Companies using a single crystalline form rather than a two-form mixture.
• Applicants pursuing a noninfringing method-of-use carve-out.

No reliable conclusion about a Paragraph IV filing, district-court litigation, or settlement agreement follows from the claim text alone. Those matters are established through FDA Orange Book records, FDA Paragraph IV notifications, PACER or RECAP filings, and public settlement documents.

What generic entry risks exist?

The principal generic-entry scenarios are:

Scenario	Likely patent issue
Same claimed crystalline form	High direct-infringement risk under claims 1-12
Different polymorph with overlapping XRPD peaks	Analytical and claim-construction dispute
Amorphous ponatinib hydrochloride	Potential design-around, subject to composition and method claims
Single-form formulation	Potential avoidance of claim 13
Two-form formulation including Form A	Direct risk under claims 13-14
Same active ingredient but different form	Method-claim risk depends on product identity and prescribing use
Carved-out indication	May reduce method-of-use exposure but does not address product claims

The strongest barrier is the solid-form claim set if the marketed product uses the patented form. A product claim can block commercial launch even when a method-of-use claim is avoided.

Is there biosimilar risk for ponatinib?

No traditional biosimilar pathway applies. Ponatinib is a chemically synthesized small molecule, not a biological product. Competitive entry would generally proceed through the ANDA pathway under Hatch-Waxman, not through a 351(k) biosimilar application. (FDA, 2024b; 21 U.S.C. §§ 355(j), 262(k))

The relevant competitive threats are generic ponatinib products, alternative salt or polymorph products, and potentially authorized-generic strategies.

How strong is the patent estate?

US 11,192,897 has moderate-to-strong value as a solid-form patent, subject to proof that the marketed ponatinib material matches the claimed form.

Factor	Assessment
Chemical-entity coverage	Limited; the claims do not broadly claim ponatinib
Solid-form coverage	Stronger; multiple independent characterization routes
XRPD breadth	Broad on wording, but vulnerable to identity and overlap disputes
Stability coverage	Potentially useful, but test-method dependent
Thermal coverage	Narrow numerical range
Formulation coverage	Moderate; requires at least two crystalline forms
Method-of-use coverage	Moderate; tied to claimed form or two-form composition
CML relevance	High commercial relevance
Ph+ ALL relevance	High regulatory relevance, but narrower patient population
Design-around potential	Meaningful through alternative solid forms and single-form products
Litigation value	Highest if the marketed product demonstrably contains the claimed form

The patent is stronger when supported by a complete XRPD fingerprint, reproducible stability data, defined Form A and other forms, and manufacturing records linking the marketed product to the claimed crystalline material.

What manufacturing and IP barriers does the patent create?

A generic manufacturer must control solid-state attributes throughout the manufacturing chain. Relevant operations include:

• Salt formation.
• Solvent selection.
• Seeding.
• Crystallization temperature.
• Cooling rate.
• Water activity.
• Drying conditions.
• Milling.
• Granulation.
• Compression.
• Storage.

Polymorph conversion can occur during drying, milling, compression, humidity exposure, or accelerated stability testing. A product that begins as a noninfringing form could convert into the claimed form during manufacture or storage.

The most credible design-around strategy is to develop and validate a distinct crystalline or amorphous form with:

• A different XRPD pattern.
• A melting profile outside claims 11 and 12.
• Stability properties that do not satisfy claims 5 through 10.
• No mixture containing Form A.
• Manufacturing controls preventing conversion to the patented form.

How does this patent compare with core ponatinib patents?

Patent layer	Typical subject matter	Relationship to US 11,192,897
Composition of matter	Ponatinib chemical structure	Broader active-ingredient protection, if unexpired
Salt or solid form	Ponatinib hydrochloride polymorphs	Directly relevant
Formulation	Tablet, excipient, dissolution, dosage form	US 11,192,897 has limited formulation coverage
Method of treatment	CML, Ph+ ALL, resistant mutations	Overlaps through claims 15-23
Manufacturing	Crystallization or purification process	Relevant only if separately claimed or incorporated through infringement evidence
Regulatory exclusivity	FDA exclusivity periods	Separate from patent protection

US 11,192,897 should be analyzed as one layer of a portfolio. It may remain commercially relevant after composition-of-matter protection expires if the marketed product uses the claimed form and the patent remains enforceable.

Key Takeaways

• US 11,192,897 is principally a crystalline-form patent for ponatinib hydrochloride.
• Claims 1 through 4 use XRPD peak combinations and are the central product claims.
• Claims 5 through 10 add heat, humidity, DVS, DSC, and HPLC stability characteristics.
• Claims 11 and 12 cover a narrow melting-temperature profile.
• Claims 13 and 14 cover compositions containing at least two crystalline forms, including Form A.
• Claims 15 through 23 cover CML and Ph+ ALL treatment methods using the claimed form or composition.
• Claims 17 and 18 contain a dependency inconsistency because they depend on chronic-phase claim 16 while reciting acute-phase and blast-phase disease.
• Ponatinib is a small molecule, so generic competition proceeds through ANDA litigation rather than biosimilar litigation.
• The commercial strength of the patent depends on whether Iclusig or a proposed generic contains the claimed crystalline form.
• A distinct polymorph, amorphous form, single-form product, or indication carve-out may reduce infringement exposure.
• Exact patent expiration, Orange Book listing, Paragraph IV activity, litigation, and settlement status require the controlling USPTO, FDA, and court records rather than the claim text alone.

FAQs About US 11,192,897 and Ponatinib Patent Protection

Does US 11,192,897 claim ponatinib itself?

No. The claims are directed to crystalline ponatinib hydrochloride forms, compositions containing multiple forms, and treatment methods using those forms.

Can a generic avoid US 11,192,897 by using amorphous ponatinib?

Potentially. An amorphous product may avoid XRPD-defined crystalline-form claims, but it must also be evaluated against the stability, melting-point, composition, and method claims.

Does a three-peak XRPD match automatically establish infringement?

No. The product must satisfy all limitations of the applicable claim, and the analytical result must be interpreted using the patent’s specification and accepted testing methodology.

Can a generic launch after submitting a Paragraph IV certification?

Not automatically. The patent holder may file an infringement action, which can trigger the Hatch-Waxman 30-month stay under applicable conditions. The launch date then depends on litigation, court orders, settlements, and regulatory approval. (21 U.S.C. § 355(j)(5)(B)(iii))

Are claims 15 through 23 limited to FDA-approved ponatinib indications?

The claims are limited by their recited disease and patient characteristics, but patent claim scope and FDA labeling scope are separate. Infringement depends on the patented form, the administered product, the method of use, and the evidence of intended use.

References

1. U.S. Patent No. 11,192,897. (2021). Crystalline form of ponatinib hydrochloride. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

3. U.S. Food and Drug Administration. (2024b). Iclusig prescribing information. Takeda Pharmaceuticals U.S.A., Inc.

4. 21 U.S.C. § 355. (2024). New drugs and antibiotics.

5. 21 U.S.C. § 262(k). (2024). Licensure of biological products as biosimilar or interchangeable.

6. U.S. Food and Drug Administration. (2024c). Abbreviated new drug application submissions: Refuse-to-receive standards and patent certification requirements. Washington, DC.

Drugs Protected by US Patent 11,192,897

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Takeda Pharms Usa	ICLUSIG	ponatinib hydrochloride	TABLET;ORAL	203469-004	Dec 18, 2020		RX	Yes	Yes				Y		A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Takeda Pharms Usa	ICLUSIG	ponatinib hydrochloride	TABLET;ORAL	203469-004	Dec 18, 2020		RX	Yes	Yes				Y		A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
Takeda Pharms Usa	ICLUSIG	ponatinib hydrochloride	TABLET;ORAL	203469-004	Dec 18, 2020		RX	Yes	Yes				Y		A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
Takeda Pharms Usa	ICLUSIG	ponatinib hydrochloride	TABLET;ORAL	203469-001	Dec 14, 2012		RX	Yes	No				Y		A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

International Family Members for US Patent 11,192,897

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013204506
Australia	2016210725
Australia	2018201013
Australia	2019240721