United States Patent 10,463,740: Itraconazole Matrix Formulation Claims, Scope, and Patent Landscape

U.S. Patent No. 10,463,740 covers low-dose oral itraconazole formulations using a polymer-containing matrix system and defined pharmacokinetic performance. Its commercial significance is concentrated in formulations containing approximately 50 mg to 100 mg of itraconazole, particularly solid dosage forms containing 50 mg to 70 mg per unit. The patent does not claim itraconazole itself, conventional 100 mg pellet capsules, or every itraconazole treatment method. It targets a formulation platform intended to deliver exposure comparable to, or greater than, a 100 mg itraconazole pellet capsule under fed and fasting conditions.

The strongest commercial claims are claims 1, 21, and their dependent claims covering the formulation, dose, matrix, and pharmacokinetic profile. Claims 13 through 20 extend the estate to therapeutic use, including fungal infections and specified cancers.

What does U.S. Patent 10,463,740 protect?

The patent protects an oral itraconazole composition that satisfies four principal elements:

It contains approximately 50 mg to 100 mg of itraconazole.
It contains one or more pharmaceutically acceptable polymers.
The polymers are present in a matrix system.
The formulation achieves specified AUC, Cmax, bioavailability, or therapeutic-similarity results.

The independent composition claims are claims 1 and 21. Claim 1 uses “about 50 mg to about 100 mg,” while claim 21 states “50 mg to 100 mg.” Both claims use pharmacokinetic performance as a substantive limitation.

Claim architecture

Claim group	Subject matter	Principal limitation
1	Independent composition	50-100 mg itraconazole, polymer matrix, fed-condition AUC
2	Composition	Non-gelling polymer
3-5	Solid dosage form	50-75 mg, or 50-70 mg, per unit
6-7	Pharmacokinetics	Fed and fasting AUC ranges
8	Comparative pharmacokinetics	AUC ratio against a 100 mg pellet capsule
9	Pharmacokinetics	Fed-condition Cmax
10-11	Therapeutic similarity	Fed and fasting comparisons
12	Variability	Reduced AUC, Cmax, or Tmax variability
13	Independent method claim	Treatment using the composition
14-15	Therapeutic indications	Fungal infection and selected cancers
16-19	Method limitations	Non-gelling polymer, solid form, dose limitations
20	Relative bioavailability	Frel greater than approximately 150%
21-22	Independent and dependent composition claims	50-100 mg, with 50-70 mg narrower range

How broad are the composition claims?

Claim 1 is structurally broad but functionally constrained. It does not identify a particular polymer, polymer ratio, manufacturing process, particle-size distribution, dissolution profile, or release mechanism. A formulation can therefore fall within the claim without using a named polymer, provided it has a polymer matrix and meets the stated pharmacokinetic limitations.

The principal structural scope is:

Oral administration.
Itraconazole as the active ingredient.
Approximately 50 mg to 100 mg per composition.
One or more pharmaceutically acceptable polymers.
A matrix system.
Defined fed-condition AUC.

The claim does not expressly require:

A capsule.
A tablet.
A particular salt or polymorph.
Sugar spheres.
Hydroxypropyl methylcellulose.
Polyethylene glycol.
A non-gelling polymer in the independent claim.
A specific itraconazole particle size.
A specific dissolution specification.
A particular excipient concentration.
A particular manufacturing process.

This drafting approach creates a broad formulation claim, but the pharmacokinetic limitation may make infringement more difficult to establish without product testing or clinical data.

What is the practical scope of the matrix limitation?

The matrix requirement separates the claimed technology from a conventional multiparticulate pellet capsule in which itraconazole is layered onto sugar spheres. A conventional pellet capsule generally has discrete coated particles rather than a unitary polymer matrix.

The patent therefore creates risk for:

Tablets containing itraconazole dispersed through a polymer matrix.
Matrix-based capsules.
Granules or pellets in which the active is incorporated into a polymeric matrix.
Solid dispersions that meet the matrix interpretation and pharmacokinetic limitations.
Low-dose formulations designed to match the exposure of a higher-dose conventional capsule.

The scope is less certain for:

Liquid formulations.
Pure itraconazole suspensions.
Conventional sugar-sphere pellet capsules.
Lipid formulations with no polymer matrix.
Amorphous solid dispersions where the polymer is a carrier but not technically a matrix.
Multiparticulate systems in which polymer is used only as a coating.

Those products would require a claim-construction analysis based on the patent specification, prosecution history, and technical composition.

What pharmacokinetic performance does Patent 10,463,740 require?

The patent uses AUC, Cmax, relative bioavailability, therapeutic similarity, and intra-subject variability as claim limitations.

Key pharmacokinetic limitations

Claim	Parameter	Required result
1	Fed AUC0-t	80%-125% of approximately 440-1,200 h·ng/mL
6	Fed AUC0-t	80%-125% of approximately 650-1,200 h·ng/mL
7	Fasting AUC0-t	80%-125% of approximately 350-900 h·ng/mL
8	AUC ratio	Approximately 0.70-1.43, with a 90% confidence interval, versus 100 mg pellet capsule
9	Fed Cmax	80%-125% of approximately 65-100 ng/mL
10	Fed therapeutic similarity	Similar to 100 mg pellet capsule under fed conditions
11	Fasting therapeutic similarity	Similar to 100 mg pellet capsule under fed conditions
12	Variability	Reduced AUC, Cmax, or Tmax variability
20	Relative bioavailability	Greater than approximately 150% versus 100 mg pellet capsule under fed conditions

The numerical wording creates several possible claim-construction issues. For example, claim 1 can be read as requiring an AUC within 80% to 125% of a reference range extending from approximately 440 to 1,200 h·ng/mL. Depending on interpretation, the operative range could extend from approximately 352 h·ng/mL to 1,500 h·ng/mL. The patent specification and prosecution history would control whether the range is interpreted as a single composite range, a set of reference values, or a study-derived target.

Claim 8 is more specific because it requires a confidence interval for the ratio against a defined comparator. A generic applicant could challenge this limitation by arguing that the proposed product does not meet the confidence-interval requirement, even if its mean exposure is similar.

Which claims are most commercially important?

Claims 1 and 21 are the primary product claims. Claims 4, 5, and 22 are commercially important because they focus on the 50 mg to 70 mg dose range likely associated with low-dose itraconazole products.

Claim 13 is the principal method claim. Claims 14 and 15 identify fungal infection and specified cancers, including prostate, skin, and lung cancer.

The hierarchy is:

Claims 1 and 21: broad formulation protection.
Claims 4, 5, and 22: 50 mg to 70 mg solid dosage forms.
Claims 6-9: specific PK profiles.
Claims 10-12: therapeutic similarity and variability.
Claims 13-20: treatment and bioavailability claims.

The dependent claims do not all narrow the patent in the same way. Claims 10 and 11 impose a comparison to the reference pellet capsule, while claim 12 imposes a comparative variability requirement. Those limitations may be valuable commercially but can require more extensive evidence in litigation.

How does the patent compare with conventional itraconazole products?

The reference product in the claims is a 100 mg itraconazole composition containing sugar spheres, hydroxypropyl methylcellulose, and polyethylene glycol in a capsule shell. This description corresponds to the technical architecture of a conventional pellet-based itraconazole capsule, such as the type associated with Sporanox.

Attribute	Claimed formulation	Conventional pellet capsule
Itraconazole dose	Approximately 50-100 mg	Approximately 100 mg
Physical architecture	Polymer matrix	Drug-coated sugar spheres or pellets
Fed-condition comparison	Designed to match or exceed reference exposure	Reference exposure
Fasting-condition performance	Expressly addressed in claims	Food-dependent absorption
Polymer role	Matrix-forming or matrix-associated	Coating, binder, or release-control excipient
Claim focus	Dose reduction and PK performance	Conventional multiparticulate delivery

The patent's commercial theory is that a lower itraconazole dose can produce exposure comparable to a higher-dose pellet capsule. That distinction is relevant to products such as SUBA-itraconazole, marketed in the United States as TOLSURA, although product-specific coverage must be confirmed against the current FDA Orange Book and the patent's listed claims.

What is the relationship to TOLSURA and SUBA-itraconazole?

TOLSURA is a 65 mg itraconazole capsule approved by the FDA for treatment of certain systemic fungal infections. The product uses the SUBA itraconazole technology associated with improved dissolution and absorption relative to conventional itraconazole capsules. FDA labeling states that TOLSURA should be administered with a full meal and identifies clinically important differences from conventional itraconazole formulations.[1]

The 50 mg to 70 mg ranges in claims 5, 19, and 22 are particularly relevant to a 65 mg product. A product with 65 mg itraconazole in a polymer matrix is positioned close to the central commercial target of these claims.

The claims do not automatically establish that TOLSURA practices every limitation. A product-specific analysis would require comparison of:

The actual formulation and matrix structure.
The polymer identity and function.
The marketed unit dose.
Fed and fasting PK data.
The relevant reference product.
The patent's prosecution history.
Any Orange Book listing and certified claim.

What patents protect itraconazole products?

Itraconazole has multiple layers of historical and potential patent protection:

Active ingredient and early formulation patents

The original itraconazole compound and early pharmaceutical formulations are old and generally do not provide meaningful new-product exclusivity for current U.S. launches. Conventional 100 mg itraconazole capsules have also faced generic competition.

Pellet and capsule technology

Conventional itraconazole products use pellet or multiparticulate technology involving sugar spheres, polymers, and capsule shells. These technologies may be described in earlier formulation patents, but their commercial exclusivity is distinct from the low-dose matrix and PK claims in Patent 10,463,740.

Matrix and bioavailability technology

Patent 10,463,740 is directed to a later formulation concept: reducing the itraconazole dose while achieving exposure comparable to a conventional 100 mg pellet capsule. The claims combine composition structure with clinical or pharmacokinetic performance.

Method-of-use protection

Claims 13-19 cover treatment methods, but their practical value depends on the indication and the role of the product in clinical practice. Fungal-infection claims are more directly connected to the approved product label than cancer claims. The cancer claims may have limited enforcement value if the product is not promoted or prescribed for those uses.

When does U.S. Patent 10,463,740 lose exclusivity?

The patent number and grant date alone do not establish the final expiration date. U.S. patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and statutory exclusions under 35 U.S.C. §§ 154 and 156.[2]

The patent was granted on November 5, 2019. Its enforceable term must be determined from the USPTO continuity data and patent-term calculation. Any Orange Book expiration date may differ from a simple 20-year calculation because of patent-term adjustment or disclaimer issues.

Regulatory exclusivity is separate from patent term. For a drug product such as TOLSURA, FDA exclusivity may include:

New chemical entity exclusivity, if applicable.
Three-year exclusivity for a new clinical investigation supporting approval.
Orphan-drug exclusivity, if the approved indication qualifies.
Pediatric exclusivity, if granted.

FDA Orange Book listings and FDA exclusivity records control the regulatory component.[3]

Is Patent 10,463,740 listed in the Orange Book?

Orange Book status cannot be inferred solely from the claim text. The relevant question is whether the patent is listed against the applicable NDA, which claims are identified, and whether the listing remains active.

For a listed patent, an ANDA applicant may need to submit one of the following certifications:

Paragraph I: no patent information has been submitted.
Paragraph II: the patent has expired.
Paragraph III: the applicant will wait until patent expiration.
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV notice can trigger patent litigation under 21 U.S.C. § 355(j)(5)(B)(iii), generally creating a 30-month stay of FDA approval if the NDA holder or patent owner files suit within the statutory period.[4]

What generic entry risks exist?

The principal generic-entry strategies are formulation design-around, Paragraph IV litigation, and delayed launch after patent expiry.

Design-around options

A competing product could attempt to avoid the patent by using:

A dose outside the 50 mg to 100 mg range.
A conventional pellet architecture rather than a matrix.
A formulation without a polymer matrix.
A liquid or alternative dosage form.
A matrix that fails the claimed PK profile.
A different bioavailability-enhancement technology.

The 50 mg to 70 mg range is harder to avoid for a direct substitute for a 65 mg product. A dose below 50 mg or above 100 mg may avoid the literal dose limitation but could lose commercial equivalence.

Invalidity positions

Potential invalidity theories may focus on:

Anticipation by prior itraconazole matrix formulations.
Obviousness based on combining known itraconazole formulations with known polymer matrices.
Lack of written description for broad polymer or matrix language.
Enablement of the full dose and PK ranges.
Indefiniteness in the “about,” “therapeutically similar,” and comparative PK language.
Inconsistent or unclear interpretation of the AUC reference ranges.

The PK limitations may support validity by distinguishing the claims from structurally similar prior art. They can also create enablement and indefiniteness disputes if the specification does not provide adequate guidance across the full claimed formulation space.

How strong is the patent estate?

Patent 10,463,740 has moderate-to-strong blocking value against a directly substitutable 65 mg polymer-matrix product that produces the claimed exposure. Its strength is lower against products using a different architecture or dose.

Factor	Assessment
Product relevance	High for 50-70 mg matrix products
Structural breadth	Broad
PK dependence	Significant
Design-around potential	Moderate
Risk for a 65 mg matrix capsule	High
Risk for a conventional 100 mg pellet capsule	Lower
Risk for nonoral or nonmatrix products	Low
Method-claim value	Moderate, indication-dependent
Litigation proof burden	Potentially high because of PK limitations

The estate is strongest when the accused product is structurally similar and marketed as a lower-dose, improved-absorption itraconazole formulation. It is weaker when infringement depends only on achieving similar exposure without using a technically comparable matrix.

What litigation and settlement issues matter?

A complete litigation assessment requires the current USPTO, PACER, FDA Orange Book, and ANDA litigation records. The claim text alone does not establish whether a Paragraph IV notice, district-court complaint, settlement, consent judgment, or launch agreement exists.

The principal litigation questions would be:

Whether the patent is listed against the relevant NDA.
Which claims are listed.
Whether an ANDA applicant has certified Paragraph IV.
Whether the patent owner filed suit within 45 days.
Whether a 30-month stay applies.
Whether the parties entered a launch-date or license settlement.
Whether any patent-term extension or pediatric extension applies.
Whether the proposed generic uses a matrix system.
Whether the ANDA's bioequivalence data satisfy the claimed PK limitations.

Which companies are likely to be relevant competitors?

The competitive field includes:

The NDA holder and commercial sponsor of TOLSURA.
Manufacturers of conventional itraconazole capsules.
Generic pharmaceutical companies developing ANDA products.
Specialty formulation companies using amorphous dispersion, lipid, or polymer-matrix technology.
Contract manufacturers with controlled-release or solid-dispersion capabilities.

Conventional generic itraconazole capsules are not necessarily direct substitutes for a 65 mg matrix product. They may compete on price but differ in dose, absorption profile, food requirements, and labeling.

What manufacturing and IP barriers exist?

The main technical barriers are formulation reproducibility and pharmacokinetic control. A competitor must produce consistent itraconazole dispersion, matrix homogeneity, dissolution, stability, and fed-condition exposure. Itraconazole has poor aqueous solubility and complex absorption behavior, making formulation performance sensitive to particle properties, polymer selection, processing conditions, and food effects.

The patent does not expressly claim a manufacturing process. A competitor could therefore face no literal process-claim barrier under this patent while still risking infringement of the composition claims.

Key Takeaways

U.S. Patent 10,463,740 covers low-dose itraconazole oral formulations using a polymer matrix.
The commercial center of gravity is the 50 mg to 70 mg solid dosage range.
Claims 1 and 21 are the core product claims.
Claims 6-12 rely heavily on fed or fasting pharmacokinetic performance.
Claims 13-20 cover treatment methods and relative bioavailability.
A 65 mg matrix product presents the highest apparent infringement risk.
Conventional 100 mg pellet capsules are less directly implicated because the patent distinguishes matrix systems from the pellet comparator.
The patent does not expressly claim a specific polymer, manufacturing process, particle size, or release profile.
Paragraph IV risk depends on current Orange Book listing, ANDA certification, and any resulting litigation.
The statutory expiration date cannot be calculated from the supplied claims alone; USPTO term data and any Orange Book listing control.
The principal design-around routes are a nonmatrix architecture, a dose outside the claimed range, or a formulation that does not satisfy the claimed PK results.

FAQs

Does Patent 10,463,740 cover all itraconazole capsules?

No. It is directed to oral itraconazole compositions containing approximately 50 mg to 100 mg in a polymer matrix and meeting specified pharmacokinetic limitations.

Does a 65 mg itraconazole capsule automatically infringe?

No. A 65 mg product must also satisfy the polymer-matrix and pharmacokinetic limitations, along with the other elements of at least one asserted claim.

Can a conventional 100 mg itraconazole pellet capsule infringe?

Potentially, but the matrix limitation creates a substantial distinction. A conventional sugar-sphere pellet capsule may not meet the claimed matrix requirement.

Are the cancer method claims commercially significant?

They may provide additional claim coverage, but their practical value depends on regulatory labeling, physician use, promotion, and proof of infringement. The fungal-infection claims are more closely aligned with the approved product use.

Does similar bioavailability alone establish infringement?

No. Similar bioavailability does not establish infringement unless the accused product also satisfies the structural and pharmacokinetic limitations of the asserted claim.

References

U.S. Food and Drug Administration. (2024). TOLSURA (itraconazole) capsules: Prescribing information.
United States Code, 35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
United States Code, 21 U.S.C. § 355(j).
United States Patent and Trademark Office. (2019). U.S. Patent No. 10,463,740.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mayne Pharma	TOLSURA	itraconazole	CAPSULE;ORAL	208901-001	Dec 11, 2018		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y			TREATMENT OF FUNGAL INFECTIONS, INCLUDING BLASTOMYCOSIS, HISTOPLASMOSIS, AND ASPERGILLOSIS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	2012902624	Jun 21, 2012

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013278001	⤷ Start Trial
Australia	2018201298	⤷ Start Trial
Australia	2020217438	⤷ Start Trial
Brazil	112014031706	⤷ Start Trial
Canada	2876909	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,463,740

Which drugs does patent 10,463,740 protect, and when does it expire?

Summary for Patent: 10,463,740