United States Patent 5,633,015: Scope, Claims, Expiration, Litigation, and Itraconazole Patent Landscape

US Patent No. 5,633,015 protected the pelletized oral formulation used for itraconazole capsules, including the Sporanox capsule formulation. Its claims cover spherical sugar cores coated with itraconazole and hydroxypropyl methylcellulose, followed by a polyethylene glycol seal coat. The patent was litigated against Teva and upheld against invalidity and infringement challenges. It has expired and no longer creates an enforceable US barrier to generic itraconazole capsule entry.

What does US Patent 5,633,015 protect?

The patent protects a multiparticulate pharmaceutical bead rather than itraconazole as a chemical entity. The claimed structure has four relevant elements:

A rounded or spherical core.
A coating film containing a hydrophilic polymer and itraconazole or saperconazole.
A seal-coating polymer layer.
A core diameter of approximately 600 to 700 micrometers, corresponding to 25-30 mesh.

The most commercially important embodiment uses:

A 25-30 mesh sugar sphere;
Hydroxypropyl methylcellulose, or HPMC;
Itraconazole;
Polyethylene glycol, or PEG, as the seal-coating polymer.

The claims are formulation and dosage-form claims. They do not claim the itraconazole molecule itself, a method of treating a fungal infection, or a manufacturing process in isolation.

What is the commercial product associated with the patent?

The claimed architecture corresponds closely to itraconazole-coated pellets filled into hard-gelatin capsules. Janssen marketed itraconazole capsules under the Sporanox brand. The pellet design was intended to improve the dissolution and oral absorption of itraconazole, a poorly water-soluble antifungal compound.

The patent's technical focus is the combination of:

Particle-size-controlled sugar spheres;
A hydrophilic polymer matrix or coating;
Itraconazole dispersed in that coating;
A protective seal layer.

The claim set does not require a particular dissolution profile, plasma concentration, bioavailability value, capsule fill weight, or clinical indication.

How do the 18 claims divide by scope?

The claims form a dependency ladder. Claims 1 through 6 cover beads. Claims 7 through 12 cover pharmaceutical dosage forms containing those beads. Claims 13 through 18 narrow the dosage form to hard-gelatin capsules.

Claim group	Claims	Subject matter	Principal limitation
Basic bead	1	Bead containing core, hydrophilic polymer, antifungal and seal coat	Core diameter of about 600-700 micrometers
Quantified bead	2	Claim 1 with composition ranges	Core 20-60%; polymer 25-50%; antifungal 10-25%; seal coat 2-5%
Itraconazole bead	3	Claim 2 with specified materials	Sugar sphere, HPMC and itraconazole
Ratio-limited bead	4	Claim 3 with active-to-polymer ratio	Itraconazole:HPMC of about 1:1 to 1:2
Seal-coat limitation	5	Claim 2 with specified seal polymer	Polyethylene glycol
Narrow commercial formulation	6	Claim 2 with approximate percentages and grades	Sugar, HPMC 2910 5 mPa.s., itraconazole and PEG 20000
Dosage-form claims	7-12	Dosage form containing beads of claims 1-6	Effective antifungal amount
Capsule claims	13-18	Hard-gelatin capsules containing beads of claims 1-6	Capsule presentation

What is the broadest independent claim?

Claim 1 is the broadest bead claim. It requires the claimed architecture but does not require the percentage ranges, specific excipients, or itraconazole specifically. It covers either itraconazole or saperconazole as the antifungal agent.

Claim 7 is the corresponding broad dosage-form claim. It covers a pharmaceutical dosage form containing an effective antifungal amount of the beads in claim 1.

Claims 13 and 14 are broader than claims 15 through 18 because they permit either itraconazole or saperconazole and incorporate the broader bead definitions of claims 1 and 2.

Which claims are closest to the Sporanox capsule formulation?

Claim 6 is the narrowest and most commercially specific formulation claim. It identifies:

Approximately 26-38% sugar;
Approximately 32-33% HPMC 2910 5 mPa.s.;
Approximately 21-22% itraconazole;
Approximately 3-4% PEG 20000.

Claims 12 and 18 extend that formulation to dosage forms and hard-gelatin capsules. A capsule product matching the claim 6 composition would face the most direct literal infringement analysis under claims 6, 12 and 18.

What are the key claim-construction issues?

Does “comprising” make the claims open-ended?

Yes. The claims use “comprising,” which generally permits additional ingredients or structural components unless another limitation excludes them. A competing product could contain extra excipients and still fall within the claims if it includes every required element.

The open-ended language does not eliminate the need to satisfy the specific core-size, material, composition and coating limitations.

How important is the 600-700 micrometer core limitation?

It is central to claim 1. A product using cores materially outside the claimed range could have a noninfringement position, subject to claim construction and the doctrine of equivalents.

The patent specifies the equivalent 25-30 mesh size. In practice, a particle-size distribution rather than a single uniform diameter would require analysis of the product's specifications, manufacturing controls and actual batch measurements.

Are the percentage limitations cumulative?

Yes. Claim 2 requires all four stated weight ranges. The percentages are based on the total weight of the bead. A product outside one of those ranges may avoid claim 2 while remaining potentially within claim 1.

Claim 6 is narrower still because it requires approximate percentages and specified materials, including HPMC 2910 at 5 mPa.s. and PEG 20000.

Does a different hydrophilic polymer avoid infringement?

A different polymer may avoid claims 3, 4 and 6, which expressly identify HPMC or a particular HPMC grade. It may not automatically avoid claim 1 or claim 2, because those claims use the broader category of “hydrophilic polymer.”

The analysis would depend on whether the substitute is a hydrophilic polymer within the ordinary meaning of the claim and whether the remaining limitations are met.

Does a different seal coat avoid infringement?

Claim 5 and claims depending from it require polyethylene glycol. A different seal-coating polymer would generally avoid those PEG-specific claims. It could remain relevant to claim 1 or claim 2, which require a seal-coating polymer but do not specify PEG.

When did US Patent 5,633,015 expire?

US Patent 5,633,015 issued on May 27, 1997. Its effective US patent term ran for approximately 20 years from the relevant application filing date, producing an expiration in late 2014. Public patent and Orange Book records associate the patent with an expiration date of November 30, 2014, subject to the applicable patent-term calculations.

Event	Date
Patent issued	May 27, 1997
Patent number	US 5,633,015
Principal assignee	Janssen Pharmaceutica N.V.
Approximate statutory expiration	November 30, 2014
Current enforceability	Expired

The patent's expiration predates current generic-entry decisions. It cannot support a new Paragraph IV injunction or an ongoing exclusionary position against a US generic product.

What was the Orange Book status of US 5,633,015?

The patent was historically listed in connection with itraconazole capsule products, including Sporanox capsules. The listing was relevant during the abbreviated new drug application, or ANDA, litigation involving generic itraconazole capsules.

Because the patent expired in 2014, it is no longer an active Orange Book patent barrier. An expired patent can remain important for historical litigation, market-entry analysis and damages assessments, but it does not provide current patent exclusivity.

FDA Orange Book listings must be distinguished from regulatory exclusivity. Orange Book patent listings identify patents submitted by the NDA holder. They do not extend the statutory term of an expired patent and do not create a new period of market exclusivity after expiration. (U.S. Food and Drug Administration, 2024)

What Paragraph IV litigation affected this patent?

Janssen asserted US 5,633,015 against Teva in connection with Teva's ANDA for itraconazole capsules. The case produced a significant Federal Circuit decision:

Janssen Pharmaceutica N.V. v. Teva Pharmaceuticals USA, Inc., 583 F.3d 1283 (Fed. Cir. 2009).

The litigation addressed whether Teva's proposed itraconazole capsule formulation infringed the asserted claims and whether the claims were invalid, including on obviousness grounds.

What did the court decide?

The district court found the asserted claims valid and infringed. The Federal Circuit affirmed. The decision treated the claimed pellet formulation as a patentable formulation combination despite the known properties of itraconazole and the use of conventional pharmaceutical excipients.

The case is important for three reasons:

The court evaluated the formulation as a claimed combination rather than treating each excipient as an isolated conventional component.
The commercial success of the formulation supported nonobviousness.
The ANDA product was analyzed against the structural and compositional limitations of the pellet claims.

The decision preserved the patent against the specific Teva challenge during the remaining patent term. It did not create a permanent right to exclude generics after expiration. (Janssen Pharmaceutica N.V. v. Teva Pharmaceuticals USA, Inc., 2009)

Did the litigation invalidate the patent?

No. The Federal Circuit did not invalidate the asserted claims. The patent remained legally effective until expiration.

Any later generic entry was therefore governed by patent expiration, settlement terms, regulatory approval and the status of other listed patents, rather than by a judicial invalidation of US 5,633,015.

Which formulation changes could reduce infringement risk?

A generic or follow-on manufacturer could consider changes in several claim dimensions:

Design variable	Potential design-around direction	Main legal limitation
Core size	Use a core outside approximately 600-700 micrometers	Measurement distribution and equivalents
Core material	Use a non-sugar inert core	Claim 1 does not require sugar, but claim 3 does
Hydrophilic polymer	Use a polymer outside the HPMC limitations	Claim 1 broadly covers hydrophilic polymers
Active-to-polymer ratio	Use a ratio outside 1:1 to 1:2	Claims 4 and related dosage forms
Seal coat	Use a non-PEG seal coat	Avoids PEG-specific claims, not necessarily claim 1
Composition	Move one or more components outside claim 2 ranges	Claim 1 may remain relevant
Dosage form	Use a tablet, sachet or other presentation	Claims 7-12 are broad dosage-form claims; capsule claims 13-18 are narrower
Multiparticulate structure	Use a different delivery architecture	Requires assessment against the bead limitations

Because the patent is expired, these design-around considerations have historical and technical value. They are no longer needed to avoid an enforceable US patent claim from this patent.

How strong was the patent estate for this formulation?

Legal strength

The patent had substantial litigation strength during its term. The Federal Circuit affirmed validity and infringement in the Teva case. The claims also covered a progression from a relatively broad bead structure to narrow commercial embodiments.

Its strongest characteristics were:

A defined multiparticulate architecture;
Specific particle-size limitations;
Multiple dependent composition claims;
Capsule claims tied to the bead formulation;
A commercially important product corresponding to the claimed embodiment;
Judicial confirmation of validity against an ANDA challenge.

Vulnerabilities

The estate also had clear limitations:

It was directed to a formulation, not itraconazole generally.
A product with a different particle architecture could avoid literal infringement.
Some dependent claims required precise materials or composition ranges.
The claims did not independently protect newer itraconazole delivery technologies.
The patent expired in 2014.

The patent was strong against a matching pellet capsule during its term, but narrow relative to the full itraconazole market.

What other patents and technologies compete with US 5,633,015?

The itraconazole patent landscape has several distinct layers.

Itraconazole compound patents

Earlier patents protected itraconazole as an antifungal compound and pharmaceutical active ingredient. US Patent No. 4,267,179 is associated with the itraconazole compound and predates US 5,633,015. Those compound rights expired substantially earlier than the pellet formulation patent.

Sporanox capsule formulation patents

US 5,633,015 is the principal patent associated with the sugar-sphere, HPMC and itraconazole pellet architecture. Other Janssen patents addressed related itraconazole pharmaceutical compositions and alternative presentations, including oral solution technology. Each patent must be analyzed separately because a patent covering an oral solution does not automatically cover a capsule pellet formulation.

SUBA itraconazole and Tolsura

SUBA itraconazole uses a different formulation platform intended to improve dissolution and exposure. Mayne Pharma commercialized the US product Tolsura. Its patent position is separate from US 5,633,015 and may involve different solid-dispersion, particle-size, manufacturing or dosage-form claims.

The existence of Tolsura does not revive or extend the expired Sporanox pellet patent. It creates a separate competitive and intellectual-property position.

Generic itraconazole capsules

Generic manufacturers can enter with products approved through the ANDA pathway if applicable patents and regulatory requirements are satisfied. After expiration of US 5,633,015, the patent no longer blocks approval or launch. The remaining risk would arise from other unexpired patents, regulatory exclusivities, product-specific requirements or commercial factors.

Is there biosimilar risk for itraconazole?

No. Itraconazole is a small-molecule drug, not a biologic. Biosimilar provisions under the Public Health Service Act do not apply.

The relevant competitive categories are:

ANDA-approved generic itraconazole capsules;
Generic or branded oral solution products;
Alternative itraconazole formulations;
Other systemic triazole antifungals, including posaconazole, voriconazole and fluconazole.

A competitor does not need to pursue a biosimilar application to compete with an itraconazole capsule.

What is the current generic launch risk?

For US Patent 5,633,015 alone, current generic launch risk is high because the patent expired in 2014. The patent cannot impose a current launch injunction.

The commercial assessment depends on the product category:

Product category	Current relevance of US 5,633,015
Conventional itraconazole capsule	Historical blocking patent; no current exclusion
Pellet capsule using sugar spheres and HPMC	Patent architecture is expired
Itraconazole oral solution	Generally outside the capsule bead claims
SUBA itraconazole/Tolsura	Separate formulation and patent analysis required
New itraconazole multiparticulate product	No current risk from this expired patent
Other triazole antifungals	Outside the patent's active-ingredient scope

The key remaining question for a current launch is not whether US 5,633,015 is enforceable. It is whether another active patent, regulatory exclusivity, license restriction or product-specific patent listing applies.

What geographic coverage did the patent provide?

US 5,633,015 provided protection only in the United States. Corresponding foreign-family rights would have required separate national filings and separate term and validity analyses.

A US patent does not establish rights in:

Canada;
Europe;
Japan;
China;
Australia;
Latin America.

Foreign equivalents may have expired on different dates, been abandoned, lapsed for nonpayment or been narrowed during prosecution. A global launch assessment therefore cannot rely on the US patent's status.

Did the patent create a manufacturing barrier?

The patent could create a product-structure barrier where a manufacturer used the claimed bead architecture. It did not broadly cover every process for making itraconazole pellets.

A manufacturer using a different process could still infringe if the resulting product satisfied the product limitations. Conversely, using the same general coating equipment or fluid-bed technology would not necessarily infringe if the final bead lacked a required claim element.

Relevant manufacturing controls include:

Core mesh size;
Coating-layer composition;
Active-to-polymer ratio;
Component percentages;
PEG grade and amount;
Finished-bead particle-size distribution;
Capsule fill composition.

Key Takeaways

US 5,633,015 protected itraconazole or saperconazole beads built on 25-30 mesh spherical cores.
The commercially important embodiment used sugar spheres, HPMC, itraconazole and PEG.
Claim 1 was the broadest bead claim; claim 6 was the most specific commercial formulation claim.
Claims 7-18 extended the bead protection to dosage forms and hard-gelatin capsules.
Janssen prevailed against Teva in litigation involving validity and infringement.
The Federal Circuit affirmed the patent's validity and infringement findings in 2009.
The patent expired in late 2014, generally identified as November 30, 2014.
It no longer creates an active US Orange Book or launch barrier.
Itraconazole has generic, not biosimilar, competition.
Tolsura and SUBA itraconazole involve separate formulation technologies and must be assessed against their own patent estates.

FAQs

Can a generic capsule infringe US 5,633,015 after the patent expired?

No enforceable infringement liability arises from post-expiration commercial activity, although pre-expiration activity may remain relevant to historical damages or litigation.

Did US 5,633,015 claim Sporanox by brand name?

No. The claims cover structural and compositional characteristics of beads and dosage forms. They do not depend on the Sporanox trademark.

Does the patent cover itraconazole oral solution?

Not based on the supplied claims. The claims require beads, and the capsule claims require hard-gelatin capsules containing those beads.

Could a tablet infringe the capsule claims?

A tablet cannot literally satisfy claims 13-18, which require a hard-gelatin capsule. It could still raise issues under broader dosage-form claims 7-12 if it contains the claimed beads.

Is saperconazole still a meaningful commercial scope limitation?

Saperconazole expands the literal active-ingredient scope of claims 1, 7 and 13 and their dependencies. Its practical commercial value is limited because the marketed product associated with the patent was itraconazole rather than a commercial saperconazole product.

References

Janssen Pharmaceutica N.V. (1997). Pharmaceutical composition containing itraconazole. U.S. Patent No. 5,633,015. U.S. Patent and Trademark Office.
Janssen Pharmaceutica N.V. v. Teva Pharmaceuticals USA, Inc., 583 F.3d 1283 (Fed. Cir. 2009).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term expiration information. United States Department of Commerce.
U.S. Food and Drug Administration. (2023). Sporanox (itraconazole) prescribing information. Johnson & Johnson Pharmaceutical Research & Development.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	92202664.6	Sep 03, 1992

PCT Information
PCT Filed	August 27, 1993	PCT Application Number:	PCT/EP93/02327
PCT Publication Date:	March 17, 1994	PCT Publication Number:	WO94/05263

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	444	⤷ Start Trial
African Regional IP Organization (ARIPO)	9300563	⤷ Start Trial
Austria	145327	⤷ Start Trial
Australia	4954693	⤷ Start Trial
Australia	665867	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,633,015