Details for Patent: 9,192,581

Which drugs does patent 9,192,581 protect, and when does it expire?

Patent 9,192,581 protects UCERIS and is included in one NDA.

This patent has twenty-six patent family members in seventeen countries.

Summary for Patent: 9,192,581

Title:	Controlled release and taste masking oral pharmaceutical composition
Abstract:	Controlled release and taste masking compositions containing one or more active principles inglobated in a three-component matrix structure, i.e. a structure formed by successive amphiphilic, lipophilic or inert matrices and finally inglobated or dispersed in hydrophilic matrices. The use of a plurality of systems for the control of the dissolution of the active ingredient modulates the dissolution rate of the active ingredient in aqueous and/or biological fluids, thereby controlling the release kinetics in the gastrointestinal tract.
Inventor(s):	Roberto Villa, Massimo Pedrani, Mauro Ajani, Lorenzo Fossati
Assignee:	Cosmo Technologies Ltd
Application Number:	US14/491,363
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,192,581
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 9,192,581: Budesonide Extended-Release Tablet Patent Scope, Expiration, Litigation and Generic Risk

US Patent 9,192,581 protects a 9 mg budesonide tablet designed to release drug in the colon for ulcerative colitis. Its principal limitation is not budesonide alone. The patent requires a specific multipart formulation architecture, a gastro-resistant coating, hydrophilic-matrix extended release, and clinical pharmacokinetic performance measured by AUC, colonic availability, Tmax, or metabolite excretion.

The patent is associated with the Uceris budesonide extended-release product. Its nominal patent expiration is March 7, 2028, subject to any applicable patent-term adjustment. The patent is materially narrower than a broad budesonide composition patent because infringement depends on both formulation structure and claimed in-human pharmacokinetic results.

What drug and formulation does US Patent 9,192,581 protect?

Patent 9,192,581 protects an oral 9 mg budesonide tablet for colonic delivery and extended release. The claimed product has four central elements:

1. A tablet dosage form.
2. An extended-release core containing a homogeneous dispersion of granules in a hydrophilic matrix.
3. Granules containing budesonide, a lipophilic or inert component, and an amphiphilic component.
4. A gastro-resistant coating that controls release and dissolves at approximately pH 7.2.

The claims identify the formulation as a colon-targeted product for treatment of ulcerative colitis. The excipient structure points to a multimatrix or MMX-type delivery platform in which coated drug granules are distributed through a hydrophilic matrix.

The disclosed formulation elements include:

Formulation element	Claimed requirement
Active ingredient	9 mg budesonide
Dosage form	Tablet
Core	Extended-release core
Internal structure	Homogeneous dispersion of granules in hydrophilic matrix
Granule components	Lipophilic or inert component plus amphiphilic component
Hydrophilic matrix	Hydroxypropylcellulose
Lipophilic/amphiphilic materials	Lecithin and stearic acid
Coating	Gastro-resistant coating
Coating pH	Dissolves at approximately pH 7.2
Coating polymers	Methacrylic acid copolymer types A and B
Plasticizer	Triethyl citrate
Other coating materials	Talc and titanium dioxide
Additional core excipients	Microcrystalline cellulose, lactose, silicon dioxide and magnesium stearate

The patent does not broadly cover every oral budesonide product. A conventional delayed-release capsule, an immediate-release tablet, or a formulation releasing primarily in the ileum would not necessarily satisfy these structural limitations.

How many independent claims does US Patent 9,192,581 have?

The supplied claims contain four independent claims or independent claim branches:

Claim	Type	Principal subject matter
1	Product	9 mg budesonide tablet with AUC0-infinity and colon-release limitations
15	Method	Treatment of ulcerative colitis using the claim 1 dosage form
17	Product	Similar tablet with AUC0-t limitation
30	Method	Treatment of ulcerative colitis using the claim 17 dosage form

Claims 31 and 32 are narrow product claims depending from claims 1 and 17. They replace the alternative "lipophilic or inert component" language with the narrower requirement that the granules contain at least one lipophilic component and at least one amphiphilic component.

Claims 2-14 depend from claim 1. Claims 18-29 depend from claim 17, except that the supplied claim set does not include a counterpart to claim 13 requiring that budesonide be wholly contained in lecithin and stearic acid.

What are the strongest claim limitations in Patent 9,192,581?

The strongest narrowing limitations are the pharmacokinetic parameters and the detailed formulation requirements.

Pharmacokinetic limitations

Claim 1 requires an AUC0-infinity of approximately 16,431.2 ± 10,519.8 pg·hr/mL. Claim 17 instead requires an AUC0-t of approximately 13,555.9 ± 7,816.9 pg·hr/mL.

Dependent claims add:

• Colon availability of 84.93% to 100% of total systemic availability.
• Mean colon availability of approximately 95.88% ± 4.19%.
• Tmax of approximately 13.3 ± 5.9 hours.
• Urinary excretion of 6-beta-hydroxy-budesonide of approximately 111,061.9 ± 53,992.6 ng over 36 hours.

These limitations create a product-by-performance claim. A competing product may use similar excipients yet avoid infringement if it does not produce the claimed clinical profile. The reverse is also possible: a formulation with different manufacturing details could present risk if it satisfies the claimed structure and produces the claimed pharmacokinetics.

Formulation limitations

The principal formulation limitations are:

• Granules dispersed homogeneously through a hydrophilic matrix.
• Budesonide incorporated at least partly, and in one dependent claim wholly, in lecithin and stearic acid.
• Hydroxypropylcellulose in the granules or hydrogel matrix.
• A pH-dependent gastro-resistant coating using methacrylic acid copolymers.
• A coating that dissolves at about pH 7.2.

These limitations distinguish the patent from a simple enteric-coated budesonide tablet. They also make manufacturing-process evidence important in a patent dispute because the finished dosage form may not reveal every internal component or distribution characteristic.

What does claim 1 cover?

Claim 1 covers a 9 mg budesonide tablet with the following combined profile:

• Budesonide is present in granules.
• The granules contain at least one lipophilic or inert component and at least one amphiphilic component.
• The granules are dispersed homogeneously in a hydrophilic matrix.
• The tablet has a gastro-resistant coating.
• The product releases budesonide in the colon.
• The product produces the specified AUC0-infinity in humans after a single dose.
• The product is effective for treating ulcerative colitis.

The claim is cumulative. Each limitation must be present for literal infringement. The phrase "at least one lipophilic or inert component" is broader than the narrower wording in claims 31 and 32 because it can be satisfied by a lipophilic component, an inert component, or potentially both, depending on claim construction.

What does claim 17 add compared with claim 1?

Claim 17 is a parallel product claim. It uses AUC0-t rather than AUC0-infinity as the principal pharmacokinetic limitation.

Issue	Claim 1	Claim 17
AUC measurement	AUC0-infinity	AUC0-t
AUC value	About 16,431.2 ± 10,519.8 pg·hr/mL	About 13,555.9 ± 7,816.9 pg·hr/mL
Colon-release requirement	Yes	Yes
Tablet and granule architecture	Yes	Yes
Gastro-resistant coating	Yes	Yes
Ulcerative-colitis use	Expressly stated	Expressly stated

The parallel claim structure gives the patent owner two pharmacokinetic routes for asserting product coverage. A generic applicant challenging one AUC limitation would still need to address the alternative AUC0-t claim.

Which dependent claims are most commercially important?

Claims 6-10 and 22-26 define the coating system. Claims 11-16 and 27-29 define the core and granule composition.

The most commercially relevant dependent claims are:

• Claims 6 and 22: coating dissolves at pH 7.2.
• Claims 7 and 23: mixture of methacrylic acid copolymer types A and B.
• Claims 8 and 24: triethyl citrate.
• Claims 11 and 27: hydroxypropylcellulose hydrogel composition.
• Claims 12, 13 and 28: lecithin and stearic acid incorporation of budesonide.
• Claim 16: microcrystalline cellulose, lactose, silicon dioxide and magnesium stearate.
• Claims 31 and 32: lipophilic, rather than merely inert, granule component.

These claims provide fallback positions if a court narrows or invalidates the broadest product claims.

When does Patent 9,192,581 expire?

The patent’s nominal expiration date is March 7, 2028, based on the earliest claimed priority date of March 7, 2008 and the 20-year patent term measured from the relevant nonprovisional filing framework. The operative expiration date should be read with the USPTO patent-term calculation because patent-term adjustment can change the date.

Event	Date
Earliest priority date	March 7, 2008
US patent issuance	November 24, 2015
Nominal expiration	March 7, 2028
FDA product	Uceris budesonide extended-release tablets
Active ingredient	Budesonide
Dosage strength	9 mg

The patent does not create biologic-style regulatory exclusivity. Budesonide is a small molecule, and competing products proceed through the abbreviated new drug application pathway rather than the biosimilar pathway.

What is the FDA and Orange Book status of the budesonide product?

The FDA approved Uceris extended-release tablets, 9 mg, under NDA 203634 for induction of remission in adults with active, mild-to-moderate ulcerative colitis.[2][4]

The product is an oral small-molecule tablet. Its regulatory profile is distinct from Entocort EC, another budesonide product with a different dosage form and release site. Entocort EC uses delayed-release capsules and is associated with ileal and ascending-colon delivery rather than the MMX-type colonic release profile associated with Uceris.

Patent 9,192,581 has been associated with the Uceris Orange Book patent estate. Orange Book-listed patents may create a 30-month stay when a first applicant submits a valid Paragraph IV certification and the NDA holder or patent owner files suit within the statutory period.[3] The specific Orange Book listing and expiration data should be evaluated together with the current FDA Orange Book entry because listings can change through delisting, correction or expiration.

What FDA exclusivity protected Uceris?

Uceris received FDA approval in 2013. Its initial regulatory protection was separate from the later patent term. The product’s principal commercial protection arose from the combination of:

• New drug approval under NDA 203634.
• Orange Book-listed formulation and method-of-use patents.
• Patent litigation and potential Paragraph IV stays.
• The technical difficulty of reproducing colonic release and the claimed pharmacokinetic profile.

FDA exclusivity does not extend the patent term. Once regulatory exclusivity and enforceable patents no longer block approval, an ANDA applicant can obtain approval if it satisfies the applicable bioequivalence and certification requirements.

Which companies challenged Uceris patents?

Uceris has been exposed to generic competition from manufacturers seeking approval for budesonide extended-release tablets. The relevant challenger universe includes major generic companies that filed ANDAs for the 9 mg product, including firms such as Actavis/Teva, Mylan, Amneal, Zydus and other ANDA sponsors identified in FDA approval and court records.

The central litigation issues in Uceris patent cases have generally included:

• Obviousness of the multimatrix formulation.
• Anticipation and written-description support for the pharmacokinetic limitations.
• Enablement of the claimed human AUC and colon-availability results.
• Whether an ANDA product would meet the pH-dependent coating limitations.
• Whether the proposed product would infringe method-of-use claims.
• Whether a generic applicant’s Paragraph IV certification triggered a 30-month stay.

Because the supplied record does not identify a particular ANDA or defendant, no single litigation outcome can be attributed to Patent 9,192,581 alone. Uceris disputes often involved multiple patents in the product estate, meaning that a judgment on one patent did not necessarily resolve all generic-entry barriers.

What Paragraph IV risks does Patent 9,192,581 create?

A Paragraph IV challenge to Patent 9,192,581 would likely attack both validity and infringement.

Likely validity issues

A generic applicant could argue that the claims are invalid because:

• The claimed combination of enteric coating, hydrophilic matrix and budesonide granules was obvious.
• Prior art disclosed colon-targeted budesonide tablets.
• The PK ranges are inherent results of an obvious formulation.
• The specification does not enable the full breadth of the claimed AUC and colon-availability ranges.
• The claim language lacks adequate written-description support for all covered excipient combinations.
• The use of "about" creates an indefinite boundary when combined with broad standard deviations.

Likely infringement issues

An ANDA applicant would focus on whether its product has:

• A homogeneous granule dispersion.
• The required lipophilic, inert and amphiphilic components.
• A coating dissolving at approximately pH 7.2.
• The claimed copolymer mixture.
• The specified AUC or AUC0-t result.
• The claimed colon availability and Tmax.

A product label alone may not resolve all issues. Formulation composition can be assessed from the ANDA, while pharmacokinetic limitations may require comparative studies, discovery or expert analysis.

How strong is the patent estate for Uceris?

Patent 9,192,581 is technically meaningful but not broad in the manner of a composition-of-matter patent.

Strength factor	Assessment
Active ingredient exclusivity	Weak; budesonide is an established active ingredient
Dosage-form specificity	Strong; claims require a defined tablet architecture
Colon targeting	Strong; colon-release and pH-dependent coating are central limitations
Pharmacokinetic protection	Potentially strong but fact-intensive
Design-around risk	Moderate to high
Manufacturing complexity	Moderate; internal granule dispersion and coating performance matter
Method-of-use protection	Narrower than product claims and dependent on use
Biosimilar barrier	Not applicable
Generic substitution risk	High after patent and regulatory barriers fall

The patent’s principal value lies in protecting the integrated delivery system rather than budesonide itself. Its vulnerability lies in the possibility that a competitor can modify the excipient system, coating threshold, release mechanism or PK profile while maintaining therapeutic equivalence.

What formulation patents compete with Patent 9,192,581?

The closest competing patent subject matter is other budesonide delivery technology covering:

• Enteric-coated budesonide capsules.
• Multimatrix tablets.
• Hydrophilic-matrix extended-release tablets.
• Colon-targeted pH-sensitive coatings.
• Budesonide granules embedded in polymeric matrices.
• Formulations using methacrylic acid copolymers.
• Alternative release systems targeting the ileum, ascending colon or entire colon.

Entocort EC is the principal product comparator, but it is not a direct formulation equivalent. Uceris uses an extended-release tablet architecture aimed at colonic delivery. Entocort EC uses a different dosage form and release design. A generic of Entocort EC does not automatically establish noninfringement of the Uceris patent.

Mesalamine products, including Lialda, Apriso and other delayed- or extended-release products, compete therapeutically in ulcerative colitis but do not ordinarily create direct infringement risk because they do not contain budesonide or the claimed granule system.

What manufacturing and intellectual-property barriers affect generic entry?

The main manufacturing barriers are reproducibility and scale-up.

A generic manufacturer must control:

• Budesonide loading at 9 mg per tablet.
• Granule size and drug distribution.
• Lecithin and stearic-acid incorporation.
• Hydroxypropylcellulose matrix hydration.
• Homogeneous dispersion of granules.
• Coating thickness and polymer ratio.
• Dissolution onset near pH 7.2.
• Extended release through the colon.
• Batch-to-batch pharmacokinetic consistency.

These requirements can create process patents or trade-secret protection even where the core patent claims are invalidated. Manufacturing know-how may cover granulation, coating equipment, curing conditions, moisture control and dissolution testing.

Geographically, US Patent 9,192,581 applies only in the United States. Separate patent families may cover Europe, Canada, Australia and other markets. US patent expiry does not establish freedom to operate in foreign jurisdictions, and foreign claim scope may differ materially.

What generic launch scenarios exist for Uceris?

Three launch scenarios are commercially relevant.

Launch after patent expiry

A fully approved generic can enter after the relevant Orange Book patents expire, assuming no separate regulatory or patent barrier remains. The nominal date associated with Patent 9,192,581 is March 7, 2028.

Launch after successful Paragraph IV litigation

A generic may launch before patent expiry if it obtains a favorable judgment, the patent is disclaimed or delisted, or the relevant claims are otherwise removed as an obstacle.

Authorized or settlement-based launch

The brand owner and generic applicant may agree to an authorized generic, license, or settlement with a negotiated entry date. The economic terms can include royalties, supply arrangements, launch rights or restrictions on product presentation.

A settlement involving one Uceris patent does not necessarily eliminate the risk created by other Orange Book-listed patents.

What revenue exposure does Patent 9,192,581 create?

The patent protects a branded product in the ulcerative-colitis market, but the patent itself does not provide a separate revenue stream. Commercial exposure depends on:

• Uceris net sales.
• The number and timing of approved generic competitors.
• Generic substitution rates.
• The presence of authorized-generic supply.
• The remaining Uceris patent estate.
• Reimbursement and formulary positioning.
• The ability of competitors to match the product’s release profile.

Bausch Health reports Salix business performance at a segment level, and product-level Uceris revenue may not be separately disclosed in every reporting period.[5] The financial risk is therefore better modeled through branded sales exposure and erosion scenarios than through an isolated valuation of Patent 9,192,581.

Key Takeaways

• Patent 9,192,581 covers a 9 mg budesonide extended-release tablet for colonic delivery, not budesonide generally.
• The core claim requires granules dispersed in a hydrophilic matrix and a pH-sensitive gastro-resistant coating.
• Lecithin, stearic acid and hydroxypropylcellulose are important dependent-claim limitations.
• Claims 1 and 17 use different PK endpoints: AUC0-infinity and AUC0-t.
• The pharmacokinetic limitations can strengthen product protection but make infringement fact-intensive.
• Claims 15 and 30 cover treatment of ulcerative colitis using the claimed dosage form.
• The nominal expiration date is March 7, 2028.
• The patent is relevant to Uceris, FDA NDA 203634, and its Orange Book estate.
• Entocort EC is a therapeutic comparator but uses a different budesonide delivery architecture.
• No biosimilar pathway applies because budesonide is a small molecule.
• Generic entry can occur through patent expiry, successful Paragraph IV litigation, delisting, or a negotiated settlement.

FAQs

Does Patent 9,192,581 cover all 9 mg budesonide tablets?

No. It covers tablets that satisfy the claimed granule, hydrophilic-matrix, gastro-resistant-coating and pharmacokinetic limitations.

Can a generic avoid Patent 9,192,581 by changing lecithin or stearic acid?

Potentially. Claims that expressly require lecithin and stearic acid may be avoided by a materially different formulation, but broader claims may still be relevant if the replacement components satisfy the lipophilic or amphiphilic limitations.

Is Patent 9,192,581 a method-of-use patent or a formulation patent?

It is principally a formulation patent with associated method-of-treatment claims. Claims 1 and 17 are product claims; claims 15 and 30 are treatment claims.

Does approval of a generic Entocort product clear Patent 9,192,581?

No. Entocort and Uceris use different dosage forms and release technologies. Approval of one product does not establish noninfringement of the other.

What evidence would matter most in a Patent 9,192,581 infringement dispute?

The key evidence would include the ANDA formulation, granule composition, coating polymer ratio, dissolution data, manufacturing records and human pharmacokinetic results.

References

1. United States Patent and Trademark Office. (2015). U.S. Patent No. 9,192,581: Pharmaceutical composition comprising budesonide.
2. U.S. Food and Drug Administration. (2013). Uceris (budesonide) extended-release tablets, 9 mg: Prescribing information.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (2013). Approval letter for NDA 203634, Uceris extended-release tablets.
5. Bausch Health Companies Inc. (2023). Annual report on Form 10-K.

Drugs Protected by US Patent 9,192,581

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Salix	UCERIS	budesonide	TABLET, EXTENDED RELEASE;ORAL	203634-001	Jan 14, 2013	AB	RX	Yes	Yes			Y			INDUCTION OF REMISSION IN PATIENTS WITH ACTIVE, MILD TO MODERATE ULCERATIVE COLITIS

International Family Members for US Patent 9,192,581

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	251449
Australia	5680100
Canada	2377301