Details for Patent: 5,541,171

Summary for Patent: 5,541,171

Title:	Orally administrable pharmaceutical composition
Abstract:	A solid dosage form, such as a capsule or tablet, containing a pharmacologically active agent is coated with an anionic polymer, which is insoluble in gastric juice and in intestinal juice below pH7 but soluble in colonic intestinal juice, in a sufficient amount that the oral dosage form remains intact until it reaches the colon. The preferred anionic polymer is a partly methyl esterified methacrylic acid polymer in which the ratio of free carboxylic groups to ester groups is about 1:2. The invention has particular application to dosage forms of prednisolone and salts thereof, indomethacin, ibuprofen, and, especially, 5-amino-salicylic acid.
Inventor(s):	John Rhodes, Brian K. Evans
Assignee:	Medeva Pharma Suisse SA
Application Number:	US08/448,300
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Drug Patent 5,541,171: Claim Scope, Mesalamine Formulation Coverage, Expiration, and Patent Landscape

US Patent No. 5,541,171 covers a pH-dependent, colon-targeted oral mesalamine formulation. Its central limitation is a solid dosage form coated with an anionic methacrylic acid/methyl methacrylate copolymer having approximately a 1:2 ratio of free carboxyl groups to ester groups. The coating must remain insoluble below pH 7 and dissolve in colonic fluid, releasing 5-aminosalicylic acid, also known as mesalamine, in the right side of the colon.[1]

The patent was granted July 30, 1996. Its enforceable term expired July 30, 2013, subject to any applicable patent-term adjustment or extension recorded in the official patent records. The core technology is associated with delayed-release mesalamine products such as Asacol. The patent is no longer an enforceable barrier to generic or branded formulations.

What does US Patent 5,541,171 protect?

The patent protects a formulation architecture rather than mesalamine as a molecule. The protected architecture has four principal elements:

1. Mesalamine, a pharmaceutically acceptable mesalamine salt, or a mesalamine ester.
2. A solid oral dosage form, such as a tablet or capsule.
3. An external coating containing a specific anionic copolymer.
4. A pH-release profile that prevents release in the stomach and small intestine but permits release in the colon, particularly the right side of the colon.

The claimed copolymer is an anionic copolymer of methacrylic acid and methyl methacrylate. The approximately 1:2 ratio of free carboxyl groups to ester groups corresponds to the type of pH-dependent methacrylic acid copolymer commercially associated with Eudragit S-type coatings.

The patent does not broadly cover every oral mesalamine product, every delayed-release formulation, or every enteric coating. A product must satisfy the claim limitations, either literally or under a potentially applicable doctrine-of-equivalents analysis, for infringement exposure to arise.

Which claims are independent claims?

Claims 1, 9, and 19 are the principal composition claims. Claims 7 and 18 are method-of-treatment claims.

Claim	Type	Principal scope
1	Independent composition claim	Mesalamine solid dosage form with a 60 to 150 micron coating, approximately 1:2 copolymer ratio, and release to the right side of the colon
2	Dependent composition claim	Coating thickness of 75 to 125 microns
3	Dependent composition claim	Coating thickness of 80 to 100 microns
4	Dependent composition claim	Coating thickness of 80 to 125 microns
5	Dependent composition claim	Coating thickness of 80 to 125 microns
6	Dependent composition claim	Capsule or tablet
7	Independent method claim	Treatment of ulcerative colitis or Crohn's disease using claim 1
8	Dependent method claim	Treatment using an 80 to 125 micron coating
9	Independent composition claim	Coated solid dosage form in which the dosage form, but not individual particles, is coated
10	Dependent composition claim	Coating thickness of 60 to 150 microns
11	Dependent composition claim	Anionic copolymer is the only coating polymer
12	Dependent composition claim	Coating thickness of 95 to 135 microns
13	Dependent composition claim	The copolymer is the only coating polymer
14	Dependent composition claim	Approximately 120 micron coating
15	Dependent composition claim	The copolymer is the only coating polymer
16	Dependent composition claim	Capsule or tablet
17	Dependent composition claim	Individual particles are uncoated
18	Independent method claim	Treatment of ulcerative colitis or Crohn's disease of the colon using claim 9
19	Independent composition claim	Solid dosage form with the specified copolymer and colon-release behavior, without an express thickness requirement

Claims 9 and 19 are materially broader than claim 1 because they do not require the 60 to 150 micron coating range in the independent claim itself. Claim 9 includes a structural distinction: the dosage form is coated, but individual particles inside it are not. Claim 19 does not include that restriction and is the broadest composition claim in the issued claim set.

How do the claims differ in technical scope?

Claim 1: thickness-limited colon-targeted formulation

Claim 1 requires all of the following:

• A non-sustained-release oral composition.
• Mesalamine, a salt, or an ester.
• Treatment of ulcerative colitis or Crohn's disease.
• A solid oral dosage form.
• A coating thickness of 60 to 150 microns.
• An anionic methacrylic acid/methyl methacrylate copolymer.
• Approximately a 1:2 free-carboxyl-to-ester ratio.
• Insolubility in gastric juice and intestinal juice below pH 7.
• Solubility in colonic intestinal juice.
• Release to the right side of the colon.

The phrase "non-sustained release" distinguishes the claimed dosage form from a formulation designed to release mesalamine gradually over an extended period. The product may be delayed-release and site-specific without being sustained-release.

Claims 2 through 5: overlapping thickness limitations

Claims 2 through 5 narrow the coating thickness. Claims 4 and 5 both specify 80 to 125 microns, creating substantial overlap. Claim 3 is narrower at 80 to 100 microns.

The thickness limitation is potentially significant in a formulation comparison. A coating that is chemically equivalent but outside the specified thickness range may avoid claims 1 through 5, depending on the scope of the broader claims and the construction of the relevant terms.

Claims 9 and 17: whole-dosage-form coating

Claim 9 covers a dosage form in which the tablet or capsule is coated, while individual particles contained within the dosage form are not coated. Claim 17 reinforces the uncoated-particle limitation.

This language distinguishes a coated tablet or capsule from multiparticulate systems in which each granule, pellet, bead, or drug particle receives its own enteric coating. A manufacturer using individually coated mesalamine pellets may have a noninfringement position against claims requiring uncoated individual particles, although other claims or later patents could remain relevant.

Claims 11, 13, and 15: single-polymer coating

These claims require the anionic copolymer to be the only coating polymer. A formulation using a second polymer, such as a film-forming polymer or a different enteric polymer, may fall outside these dependent claims. That limitation does not necessarily avoid claim 9 or claim 19, which do not require the copolymer to be the sole polymer.

Claim 19: broadest issued composition claim

Claim 19 requires:

• An oral solid dosage form.
• Mesalamine, a salt, or an ester.
• A coating containing the specified anionic copolymer.
• Approximately a 1:2 ratio of free carboxyl groups to ester groups.
• Insolubility below pH 7.
• Solubility in colonic fluid.
• Release to the right side of the colon.

Claim 19 has no express coating-thickness limitation. It also does not expressly require the individual particles to be uncoated. For historical infringement analysis, claim 19 would therefore be the principal claim to examine against a formulation using the specified copolymer and pH-release profile.

What formulations are protected by US 5,541,171?

The patent is directed to pH-dependent mesalamine tablets or capsules coated with a methacrylic acid/methyl methacrylate copolymer that dissolves at approximately pH 7 or higher. The formulation is designed to pass through the stomach and small intestine substantially intact before releasing drug in the terminal ileum or colon.

Formulation characteristic	Relevance to patent scope
Mesalamine active ingredient	Required by the composition claims
Mesalamine salt or ester	Expressly included
Tablet or capsule	Expressly covered by dependent claims
External coating on the dosage form	Central limitation
Methacrylic acid/methyl methacrylate copolymer	Central chemical limitation
Approximately 1:2 acid-to-ester ratio	Central compositional limitation
Dissolution below pH 7	Must remain insoluble
Dissolution in colonic fluid	Required functional behavior
60 to 150 micron thickness	Required by claim 1 and related dependent claims
Coating of individual particles	Excluded by claim 9 and claim 17 when particles are coated rather than left uncoated
Sustained-release matrix	Outside the stated "non-sustained release" scope of claim 1

A mesalamine product using a different active-release mechanism, such as a prodrug, a polysaccharide-degradation coating, a time-dependent coating, or a matrix system, would require a separate claim analysis.

What is the Orange Book status of US Patent 5,541,171?

US 5,541,171 was historically relevant to FDA-approved delayed-release mesalamine products, including Asacol-related products. The Orange Book identifies patents submitted by NDA sponsors for approved drug products, but Orange Book listing is product-specific and does not establish that every claim of a patent covers every product in a therapeutic category.[2]

Because the patent expired in 2013, it does not provide current patent exclusivity. The FDA Orange Book status of a patent can change as products are discontinued, patents expire, or sponsor-submitted listings are removed. Current commercial protection for mesalamine products must be assessed against the patents listed for the specific NDA, strength, dosage form, and product family.

Regulatory exclusivity and patent term are separate. Any historical FDA exclusivity period did not extend the patent beyond its operative expiration date.

When did US Patent 5,541,171 lose exclusivity?

The patent was granted July 30, 1996, and its ordinary pre-URAA patent term was 17 years from grant. On that basis, the patent expired July 30, 2013.[1]

Event	Date
US patent grant	July 30, 1996
Ordinary 17-year patent term from grant	July 30, 2013
Current enforceability	Expired
Current blocking effect on generic launch	None from this patent alone

An expired patent cannot support a new patent-infringement injunction against a later entrant. It can remain relevant to historical litigation, validity analysis, prosecution history, claim construction, and freedom-to-operate reviews concerning products launched during the patent term.

Which companies challenged mesalamine patent protection?

Generic manufacturers historically challenged branded mesalamine products through abbreviated new drug applications and Paragraph IV certifications. The relevant commercial disputes generally involved the product-specific patent portfolios of Asacol, Asacol HD, Delzicol, and related mesalamine products rather than US 5,541,171 alone.

The patent landscape included branded sponsors and manufacturers such as Procter & Gamble, Warner Chilcott, Actavis, Allergan, Zydus, Teva, Mylan, and other generic applicants. Later litigation focused on formulation, dosage strength, coating performance, and product-specific patents that followed the earlier 5,541,171 patent.

A Paragraph IV certification against a listed patent is an assertion that the patent is invalid, unenforceable, or not infringed. It is not a judicial determination. Once US 5,541,171 expired, a Paragraph IV challenge to that patent ceased to have practical launch significance, although historical challenges may have affected earlier entry dates and settlement terms.

What patent litigation affected the Asacol and mesalamine market?

The most commercially important disputes involved later patents covering specific mesalamine products, strengths, coatings, and dosage forms. Litigation concerning Asacol HD and related products continued after the expiration of US 5,541,171 because later patents could protect modified formulations or higher-strength products.

The existence of later litigation does not revive the expired patent. A generic product that avoided the later patents could launch without infringing US 5,541,171 solely because it used a similar colon-targeted mesalamine coating.

Settlement agreements in the mesalamine sector could include licensed entry dates, authorized-generic arrangements, manufacturing restrictions, or treatment of particular dosage strengths. Such agreements must be analyzed by product and patent. No settlement can extend the statutory term of US 5,541,171.

How strong is the patent estate for this technology?

Historical strength

During its term, US 5,541,171 had meaningful technical scope because it combined:

• A defined active pharmaceutical ingredient.
• A particular enteric polymer chemistry.
• A specified acid-to-ester ratio.
• A pH threshold.
• A colon-release function.
• In several claims, a measurable coating thickness.
• A right-sided-colon delivery objective.

The combination of structural and functional limitations made the patent more specific than a general claim to enteric-coated mesalamine.

Current strength

The patent has no remaining exclusionary strength because it is expired. Its current business value is limited to:

• Historical market analysis.
• Prior-art review.
• Patent-family mapping.
• Prosecution-history analysis.
• Assessment of later patents that may claim similar formulation concepts.

The patent does not create biosimilar risk. Mesalamine is a chemically synthesized small molecule, not a biologic. Competitors generally use the generic-drug pathway rather than a biosimilar pathway.

What generic entry risks exist for mesalamine products?

US 5,541,171 creates no current generic-entry risk because its term ended in 2013. The relevant risks now arise from other sources:

1. Later formulation patents.
2. Product-specific Orange Book listings.
3. Manufacturing patents covering coating processes or release testing.
4. Regulatory requirements for bioequivalence and comparative dissolution.
5. Supply and quality-control barriers involving coating thickness and pH performance.
6. Separate patents covering high-strength tablets, capsule architecture, or modified release.

A generic manufacturer using a different polymer, a different dissolution threshold, a multiparticulate dosage form, or a non-coated delivery system may avoid the principal technical limitations of 5,541,171. It must still address any unexpired patents listed for the relevant reference-listed drug.

What manufacturing and geographic barriers remain?

The patent is a United States patent. Its expiration does not determine rights in Canada, Europe, Japan, or other jurisdictions. Foreign counterparts must be reviewed separately, including national-stage applications, validation countries, supplemental protection certificates, and local patent-term adjustments.

Manufacturing risk centers on reproducibly applying the coating and achieving the specified dissolution profile. Important process variables include:

• Copolymer composition.
• Coating weight and thickness.
• Uniformity across tablets.
• Mechanical resistance during handling.
• Stability under gastric and intestinal conditions.
• Onset of dissolution at colonic pH.
• Batch-to-batch release performance.

These variables may create regulatory or commercial barriers without creating infringement liability under an expired US patent.

How does US 5,541,171 compare with later mesalamine patents?

Issue	US 5,541,171	Later mesalamine patents
Primary focus	Colon-targeted mesalamine dosage form	Product-specific strengths, coatings, formulations, or release systems
Polymer	Methacrylic acid/methyl methacrylate copolymer	May use the same or different polymers
Release threshold	Below pH 7 insoluble; colonic release	May claim different pH, dissolution, or release parameters
Thickness	Expressly required in several claims	May use coating weight, layer structure, or performance limits
Dosage form	Tablet or capsule, with whole-dosage-form distinctions	May claim tablets, capsules, pellets, or multi-unit systems
Status	Expired July 30, 2013	Must be reviewed individually
Biosimilar relevance	None	None for mesalamine small-molecule products

Key Takeaways

• US Patent 5,541,171 covers colon-targeted, delayed-release mesalamine formulations.
• The central polymer is an anionic methacrylic acid/methyl methacrylate copolymer with an approximately 1:2 free-carboxyl-to-ester ratio.
• Claim 19 is the broadest composition claim because it lacks an express coating-thickness limitation.
• Claims 9 and 17 distinguish a coated tablet or capsule from dosage forms containing individually coated particles.
• Several dependent claims require coating thicknesses between 60 and 150 microns, with narrower ranges of 75 to 125, 80 to 100, 80 to 125, 95 to 135, or approximately 120 microns.
• The patent expired July 30, 2013, and is no longer a current US barrier to generic entry.
• Current mesalamine patent risk depends on later patents listed for the specific reference-listed drug and dosage strength.
• Mesalamine is a small molecule, so biosimilar analysis is not applicable.
• Foreign rights require separate national patent and supplementary-protection review.
• Manufacturing challenges remain relevant to regulatory approval and product quality, but they do not extend the expired patent term.

FAQs About US Patent 5,541,171

Does US 5,541,171 cover all Asacol products?

No. It covers formulations satisfying the specific claim limitations. Later Asacol products, higher-strength products, and related mesalamine products may be subject to different patents.

Can a generic use Eudragit S after the patent expired?

Yes, subject to compliance with applicable FDA requirements and any unexpired patents covering the specific product. The expiration of US 5,541,171 removed that patent as a current infringement barrier.

Does the patent cover individually enteric-coated mesalamine particles?

Claims 9 and 17 are directed to a dosage form in which individual particles are not coated. A multiparticulate product with separately coated particles requires a separate claim analysis.

Is the 1:2 methacrylic acid-to-methyl methacrylate ratio required?

Yes, the claims expressly require an approximately 1:2 ratio of free carboxyl groups to ester groups. The exact interpretation depends on claim construction and analytical characterization.

Can US 5,541,171 support a Paragraph IV challenge today?

It could be identified in a historical patent certification or litigation record, but its expiration means it cannot provide a current launch-blocking patent right. Current Paragraph IV risk must be evaluated against unexpired patents listed for the applicable mesalamine reference product.

References

1. United States Patent and Trademark Office. (1996). Pharmaceutical compositions for treatment of inflammatory bowel disease, U.S. Patent No. 5,541,171.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (n.d.). FDA-approved drug labels for mesalamine delayed-release tablets and capsules. DailyMed.
4. United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure: Patent term and patent term adjustment.
5. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application approvals and Paragraph IV certifications.

Drugs Protected by US Patent 5,541,171

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 5,541,171

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8123573	Jul 31, 1981

International Family Members for US Patent 5,541,171

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	17189
Australia	551173
Australia	8732482
Canada	1172570
Germany	3268277