Details for Patent: 11,389,450

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Which drugs does patent 11,389,450 protect, and when does it expire?

Patent 11,389,450 protects CAVHANZA and is included in one NDA.

This patent has nine patent family members in six countries.

Summary for Patent: 11,389,450

Title:	Amorphous nilotinib microparticles and uses thereof
Abstract:	Amorphous solid dispersions and pharmaceutical compositions of the protein kinase inhibitor nilotinib. The pharmaceutical compositions may be used in methods of treating a proliferative disorder such as cancer. In some embodiments, the pharmaceutical compositions can be administered without regard to food consumption. In other embodiments, the pharmaceutical compositions can be administered at a significantly lower dose as compared to a commercially available immediate-release nilotinib formulation, while providing a comparable therapeutic effect.
Inventor(s):	Christian F. Wertz, Tzehaw Chen, Joseph McTarsney
Assignee:	Flex Pharma LLC
Application Number:	US17/238,869
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Delivery; Dosage form;

US Patent 11,389,450: Nilotinib Amorphous Solid Dispersion Patent Scope and Landscape

US Patent 11,389,450 covers reduced-dose nilotinib administration using an amorphous solid dispersion containing nilotinib free base and pH-dependent hydroxypropyl methylcellulose acetate succinate, or HPMCAS. The core commercial concept is food-independent delivery: a patient receives 60% to 80% less nilotinib than the dose required for a conventional immediate-release crystalline formulation, while maintaining therapeutically relevant exposure.

The patent is directed primarily to formulation and administration combinations, not to nilotinib as a molecule. Its broadest claims require a specific amorphous dispersion, a defined nilotinib-to-polymer range, and a reduced-dose relationship to conventional crystalline nilotinib. Claims 1 through 13 add meal timing, disease, polymer chemistry, antioxidant, dosage-form and strength limitations. Claims 14 through 28 focus on fed-versus-fasted exposure and pharmacokinetic comparability.

What does US Patent 11,389,450 claim?

The patent has two independent method claims.

Independent claim	Core subject matter	Principal limitations
Claim 1	Safe delivery of nilotinib with a meal	Amorphous dispersion; nilotinib free base; polymer containing HPMCAS; nilotinib:polymer ratio of 35:65 to 80:20; dose reduced by 60% to 80% versus conventional immediate-release crystalline nilotinib; administration and meal within less than two hours
Claim 14	Food-independent therapeutically relevant exposure	Same amorphous dispersion, HPMCAS and ratio requirements; dose reduced by 60% to 80%; delivery without regard to fed or fasted state

The claims do not cover every nilotinib formulation. They require the combination of:

1. Nilotinib in free-base form.
2. An amorphous solid dispersion.
3. One or more polymers that include pH-dependent HPMCAS.
4. A nilotinib-to-polymer weight ratio between 35:65 and 80:20.
5. A materially reduced dose relative to conventional immediate-release crystalline nilotinib.
6. In claim 1, administration near a meal.
7. In claim 14, therapeutically relevant exposure regardless of fed or fasted state.

A product that omits any one of these elements may fall outside the literal scope of the independent claims, although dependent claims and other patent-family claims may create separate exposure.

How broad is the core formulation claim?

The principal formulation limitation is an amorphous solid dispersion of nilotinib free base with HPMCAS. HPMCAS is a polymer with pH-dependent solubility. The polymer is intended to maintain the drug in a supersaturated or enhanced-solubility state under gastrointestinal conditions, where conventional crystalline nilotinib has limited and food-sensitive absorption.

The claim does not require a single HPMCAS grade in claim 1 or claim 14. The dependent claims narrow the polymer to a material having:

• Acetyl substitution of 7% to 11%; and
• Succinyl substitution of 10% to 14%.

Claims 4, 19 and corresponding claims 5 and 20 create two protection levels:

Claim category	Polymer requirement
Broad independent claims	One or more polymers comprising HPMCAS with pH-dependent solubility
Narrower claims	HPMCAS with acetyl substitution of 7% to 11% and succinyl substitution of 10% to 14%
Narrowest composition language	Polymer system consists essentially of HPMCAS

The phrase "comprises" in the independent claims permits additional polymers and excipients. The phrase "consists essentially of" in claims 5 and 20 narrows the polymer system by excluding components that materially alter the claimed formulation characteristics, while potentially permitting incidental ingredients.

What nilotinib-to-polymer ratios are protected?

The broad ratio range is 35:65 to 80:20 by weight, expressed as nilotinib:polymer.

Claim	Nilotinib:polymer ratio
Claims 1 and 14	35:65 to 80:20
Claims 9 and 24	40:60 to 70:30
Claims 10 and 25	50:50

The ratio is a major design-around boundary. A formulation containing 34% nilotinib and 66% HPMCAS would be outside the literal numerical range of the independent claims, subject to claim-construction and equivalents issues. A 50:50 formulation falls within every ratio tier and is the most concentrated express embodiment in the claims.

The ratio should be calculated using the claim-relevant quantities of nilotinib and polymer in the amorphous solid dispersion. A manufacturer could dispute infringement where the product contains multiple polymers, moisture, processing aids or excipients and the ratio depends on the denominator used.

What dosage forms and strengths are covered?

Claims 12, 13, 27 and 28 extend the method claims to oral solid dosage forms. The narrower strength limitation covers products containing 25 mg to 100 mg nilotinib.

Limitation	Scope
Dosage route	Oral
Dosage form	Solid dosage form
Nilotinib strength	25 mg to 100 mg per dosage form
Composition	Amorphous dispersion plus optional pharmaceutical additives

The claims do not expressly require a tablet, capsule, multiparticulate, granule or pellet. A solid oral product can therefore potentially fall within the claims regardless of the specific unit-dose architecture, provided the claimed dispersion and dose relationship are met.

A product containing more than 100 mg per unit may still implicate claims 1 or 14, because those independent claims do not contain the 25 mg-to-100 mg limitation. The dosage-strength limitation is confined to claims 13 and 28.

Does the patent cover a food-effect limitation?

Yes. Food effect is central to both independent claims, but the claims use different legal structures.

Claim 1: meal-linked administration

Claim 1 requires administering the composition and administering a meal within less than two hours of each other. The claim does not specify whether the drug is given before or after the meal. It also does not define the meal by calorie content, fat content or timing sequence.

A regimen may therefore satisfy claim 1 if:

• The formulation is administered shortly before a meal;
• The formulation is administered during a meal; or
• The formulation is administered shortly after a meal,

provided the two events occur within less than two hours.

Claim 14: fed-state independence

Claim 14 does not require a meal. It requires delivery of therapeutically relevant exposure without regard to whether the patient is fasted or fed. Claims 15 through 18 add pharmacokinetic limits.

Claim	Pharmacokinetic limitation
Claim 15	Fed-state Cmax within 30% of fasted-state Cmax for the claimed composition
Claim 16	Fed-state AUC within 30% of fasted-state AUC for the claimed composition
Claim 17	Fed-state Cmax within 25% of fasted-state Cmax for fasted conventional crystalline nilotinib
Claim 18	Fed-state AUC within 25% of fasted-state AUC for fasted conventional crystalline nilotinib

Claims 15 and 16 compare fed and fasted administration of the claimed amorphous formulation. Claims 17 and 18 compare fed administration of the claimed formulation with fasted administration of conventional crystalline nilotinib.

These limitations create evidentiary issues in litigation. Infringement may require clinical pharmacokinetic evidence, formulation analysis and a defined comparator product. Batch-to-batch variability, subject variability and statistical treatment could affect whether the 25% or 30% boundaries are met.

What reduced-dose limitation does US 11,389,450 impose?

The claimed administered amount must be 60% to 80% less than the amount required to deliver effective nilotinib exposure using conventional immediate-release crystalline nilotinib in the fasted state.

Mathematically, the claimed dose is approximately 20% to 40% of the conventional fasted-state dose.

Conventional dose	Claimed reduced-dose range
300 mg	60 mg to 120 mg
400 mg	80 mg to 160 mg
600 mg	120 mg to 240 mg
800 mg	160 mg to 320 mg

The claim is not limited to a fixed milligram amount. It depends on a comparison against a conventional crystalline nilotinib formulation and a therapeutically effective amount or therapeutically relevant exposure.

That relative limitation can create both strength and vulnerability:

• It strengthens the patent by tying the invention to a clinically meaningful performance result.
• It creates an infringement issue because the reference dose and exposure standard must be established.
• It may complicate enforcement against products with different dosing schedules, patient populations or pharmacokinetic targets.
• It may limit claims where the accused product uses a dose reduction outside the 60% to 80% range.

What diseases and patient populations are expressly protected?

Claims 2 and 3 identify Philadelphia chromosome-positive chronic myeloid leukemia, or Ph+ CML.

Claim 3 is narrower and covers chronic-phase Ph+ CML in patients resistant or intolerant to prior tyrosine kinase inhibitor therapy. The independent claims use the broader term "proliferative disorder," which can include disorders beyond CML if the other limitations are met.

The express disease hierarchy is:

Claim	Patient population
Claims 1 and 14	Patient suffering from a proliferative disorder
Claims 2 and 3	Ph+ CML
Claim 3	Chronic-phase Ph+ CML resistant or intolerant to prior TKI therapy

The claims are method claims. A formulation manufacturer may face indirect infringement exposure if it supplies a product with instructions, labeling or technical materials that encourage the claimed administration regimen.

What formulation additives and antioxidants are protected?

Claims 6, 7, 21 and 22 cover antioxidants in the amorphous solid dispersion at 0.001% to 2% by weight. Butylated hydroxytoluene, or BHT, is the express antioxidant limitation.

Claims 8 and 23 provide an alternative composition structure in which the amorphous solid dispersion consists essentially of nilotinib and HPMCAS. Claims 11 and 26 permit pharmaceutical additives outside the dispersion.

This creates a distinction between:

• The dispersion itself, which may be limited to nilotinib and polymer; and
• The final pharmaceutical composition, which may include additional acceptable additives.

Potential additives may include tableting agents, lubricants, glidants, coatings and stabilizers, but the supplied claims do not identify those materials individually. Their presence does not necessarily avoid infringement if the underlying dispersion satisfies the claim.

How does the patent compare with conventional Tasigna nilotinib?

Conventional Tasigna is an immediate-release crystalline nilotinib product administered under food restrictions. US Patent 11,389,450 targets a different formulation architecture and dosing strategy.

Attribute	Conventional crystalline nilotinib	Claimed formulation
Drug form	Crystalline nilotinib	Amorphous nilotinib free base
Polymer dispersion	Not required	Required
HPMCAS	Not required	Required
Food handling	Food restriction under product labeling	Meal-linked or food-independent administration
Dose objective	Conventional therapeutic dose	60% to 80% lower than conventional fasted-state dose
Release platform	Immediate-release crystalline formulation	Amorphous solid dispersion
Pharmacokinetic target	Conventional exposure	Fed/fasted comparability or therapeutically relevant reduced-dose exposure

The patent does not claim the nilotinib active ingredient broadly. It is therefore a reformulation patent layered on top of earlier compound, formulation, treatment and regulatory rights associated with nilotinib.

What is the patent landscape around this technology?

The relevant landscape has at least five layers.

Nilotinib compound patents

Earlier nilotinib patents protect the active pharmaceutical ingredient and related chemical matter. Those rights are distinct from US 11,389,450. Their expiration and regulatory exclusivity dates must be evaluated separately from the expiration date of the asserted formulation patent.

Crystalline-form patents

Crystalline polymorph, salt, solvate and particle-size patents may cover conventional nilotinib products. The present claims require nilotinib free base in an amorphous solid dispersion and therefore target a different solid-state form.

Amorphous dispersion patents

These patents generally claim drug-polymer systems, manufacturing processes, stabilization, dissolution performance or solid oral dosage forms. US 11,389,450 is unusually focused on the clinical administration result: reduced dose and reduced food effect.

Method-of-use patents

Claims 2 and 3 are method-of-use claims for Ph+ CML, especially chronic-phase patients resistant or intolerant to prior TKI therapy. They may overlap commercially with nilotinib treatment patents even where the formulation is different.

Manufacturing and process patents

The amorphous dispersion may require hot-melt extrusion, spray drying, solvent processing, controlled drying or specialized milling. Process patents can create additional barriers even where a competitor avoids the composition claims.

How strong is the patent estate based on the supplied claims?

The claim set has meaningful commercial coverage but depends heavily on proof of formulation identity and pharmacokinetic performance.

Strength factor	Assessment
Defined formulation	Strong; requires amorphous nilotinib free base with HPMCAS
Ratio coverage	Broad numerical range of 35:65 to 80:20
Food-effect coverage	Strong; separate meal and food-independent claim structures
Dose reduction	Commercially important but comparison-dependent
Disease coverage	Broad in independent claims, narrower in dependent claims
Dosage-form coverage	Broad oral solid-form language
Formulation design-around risk	Moderate; alternatives may use different polymers or crystalline drug
Proof burden	High where infringement depends on Cmax, AUC or dose comparisons
Manufacturing protection	Limited in the supplied claims; no express process claim is provided

The strongest enforcement position would likely involve a product that uses nilotinib free base, HPMCAS, a ratio near 50:50, a 25 mg-to-100 mg oral solid dose, and promotional instructions permitting administration with food or without regard to food.

When does US Patent 11,389,450 lose exclusivity?

The patent's expiration date cannot be determined accurately from the claims alone. A US patent's term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers. The issue date alone does not establish the expiration date.

The relevant exclusivity analysis must distinguish:

Right	Governing issue
Patent term	Earliest effective US or priority filing date, adjusted under US patent law
Patent-term adjustment	USPTO examination delay
Patent-term extension	Regulatory review extension, if available and granted
Regulatory exclusivity	FDA approval and exclusivity designation
Orange Book listing	Whether the approved product and patent satisfy listing requirements
Litigation stay	Whether a timely Paragraph IV notice triggers a 30-month stay

US Patent 11,389,450 is a formulation and method patent on the supplied claim text. Its listing status in the FDA Orange Book cannot be established from the claims alone. Method-of-use and formulation patents may be listed only if they meet FDA listing requirements and are tied to an approved drug product.

What Paragraph IV challenges and litigation risks exist?

A generic applicant could challenge the patent through a Paragraph IV certification if the patent is listed against an approved nilotinib product and the applicant seeks approval before patent expiration.

Likely invalidity theories would include:

1. Obviousness based on crystalline nilotinib, amorphous solid dispersions and HPMCAS formulations.
2. Lack of written description for the full 35:65 to 80:20 ratio range.
3. Lack of enablement for all polymers, dosage forms, disease states and dose comparisons.
4. Indefiniteness in terms such as "therapeutically relevant exposure," "therapeutically effective amount" and "conventional immediate-release crystalline nilotinib formulation."
5. Anticipation by earlier nilotinib dispersion or food-effect disclosures.
6. Failure to meet the claimed pharmacokinetic boundaries.

The patent holder would likely rely on the combination of reduced dose, HPMCAS pH-dependent solubility and food-effect control as the inventive contribution. A challenger would focus on whether those outcomes were predictable from known amorphous-dispersion technology and whether the claims provide adequate technical support across their full scope.

No settlement agreement, Paragraph IV notice, Abbreviated New Drug Application litigation event or final court disposition is established by the supplied claim text.

What generic launch scenarios are most plausible?

Scenario 1: Conventional crystalline generic

A generic applicant copies immediate-release crystalline nilotinib without the claimed amorphous dispersion. That product would not satisfy the central formulation limitation of claims 1 or 14, although other nilotinib patents and regulatory barriers could remain relevant.

Scenario 2: Non-HPMCAS amorphous dispersion

A competitor uses a different polymer, such as a pH-independent polymer or another enteric polymer. This design may avoid the literal HPMCAS limitation, subject to equivalents and other patent-family claims.

Scenario 3: HPMCAS dispersion outside the ratio range

A competitor uses HPMCAS but places nilotinib outside the 35:65-to-80:20 range. This is a direct numerical design-around strategy, although formulation performance and other claims must be assessed.

Scenario 4: HPMCAS formulation without the reduced-dose result

A competitor uses the claimed formulation platform but administers a conventional dose. Claims 1 and 14 require the 60% to 80% dose reduction. The product could still face infringement arguments if the marketed regimen meets the limitation through actual exposure data.

Scenario 5: Product with conventional food restrictions

A product that requires fasting and does not claim meal-linked use may reduce exposure under claim 1, but it could still implicate claim 14 if its formulation provides the specified fed-state exposure relationship.

What are the principal commercial implications?

The patent's commercial value depends on whether the formulation can support:

• Lower milligram dosing;
• Administration without fasting restrictions;
• Improved adherence;
• Reduced food-effect variability;
• Smaller tablets or lower active load;
• Competitive differentiation from conventional nilotinib;
• Extension of product life beyond compound-patent expiry.

The most important competitive question is whether a follow-on product can deliver comparable exposure with a different polymer or solid-state strategy. If HPMCAS is technically necessary to achieve the required performance, the claims provide stronger practical protection than their literal wording suggests. If several polymers can produce the same clinical result, design-around risk is higher.

Key Takeaways

• US Patent 11,389,450 is a nilotinib reformulation and administration patent.
• The core invention is an amorphous solid dispersion of nilotinib free base with pH-dependent HPMCAS.
• The broad claimed nilotinib-to-polymer ratio is 35:65 to 80:20.
• The claimed dose is 60% to 80% lower than the conventional fasted-state crystalline nilotinib dose.
• Claim 1 requires drug and meal administration within less than two hours.
• Claim 14 targets therapeutically relevant exposure without regard to fed or fasted state.
• Claims 15 through 18 impose Cmax and AUC comparability thresholds.
• Dependent claims narrow the polymer chemistry, ratio, antioxidant content, oral dosage form and 25 mg-to-100 mg strength.
• The principal design-around routes are different polymers, a different solid-state form, a ratio outside the claimed range or a regimen without the claimed dose reduction.
• Expiration, Orange Book listing, Paragraph IV activity, licensing and litigation status are not ascertainable from the claim text alone.

FAQs

Does US Patent 11,389,450 cover generic crystalline nilotinib?

No. The supplied claims require an amorphous solid dispersion containing nilotinib free base and HPMCAS. A conventional crystalline immediate-release product does not satisfy that central limitation.

Does the patent require administration with food?

Claim 1 requires administration of the drug and a meal within less than two hours. Claim 14 does not require a meal and instead covers delivery without regard to fed or fasted state.

Can a competitor avoid the patent by using a different HPMCAS grade?

Not necessarily. The independent claims broadly require HPMCAS with pH-dependent solubility. The narrower substitution ranges apply to dependent claims, not to the independent claims.

Are pharmacokinetic studies required to assess infringement?

They may be required for claims that depend on Cmax, AUC, therapeutically relevant exposure or the 60% to 80% dose-reduction comparison. Formulation testing alone may not resolve those limitations.

Does the patent protect nilotinib treatment in all cancers?

The independent claims use "proliferative disorder," but the supplied dependent claims expressly identify Ph+ CML and chronic-phase Ph+ CML in patients resistant or intolerant to prior TKI therapy. The scope for other diseases depends on the construction and proof of the independent claims.

References

1. United States Patent No. 11,389,450, claims 1-28. United States Patent and Trademark Office.

2. United States Congress. (2011). Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284.

3. United States Code. 35 U.S.C. §§ 154, 156, 271, 282.

Drugs Protected by US Patent 11,389,450

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cycle	CAVHANZA	nilotinib	TABLET, ORALLY DISINTEGRATING;ORAL	217379-001	May 29, 2026		RX	Yes	No	11,389,450					USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED PH+ CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
Cycle	CAVHANZA	nilotinib	TABLET, ORALLY DISINTEGRATING;ORAL	217379-001	May 29, 2026		RX	Yes	No	11,389,450					USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH CHRONIC PHASE AND ACCELERATED PHASE PH+ CHRONIC MYELOID LEUKEMIA RESISTANT TO OR INTOLERANT TO PRIOR THERAPY THAT INCLUDED IMATINIB, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
Cycle	CAVHANZA	nilotinib	TABLET, ORALLY DISINTEGRATING;ORAL	217379-002	May 29, 2026		RX	Yes	Yes	11,389,450					USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED PH+ CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
Cycle	CAVHANZA	nilotinib	TABLET, ORALLY DISINTEGRATING;ORAL	217379-002	May 29, 2026		RX	Yes	Yes	11,389,450					USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH CHRONIC PHASE AND ACCELERATED PHASE PH+ CHRONIC MYELOID LEUKEMIA RESISTANT TO OR INTOLERANT TO PRIOR THERAPY THAT INCLUDED IMATINIB, WHEN ADMINISTERED WITH FOOD OR IN FED STATE

International Family Members for US Patent 11,389,450

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2021212258
Australia	2026204369
Canada	3168680
Canada	3313023
European Patent Office	4096791