United States Drug Patent 4,496,553: Scope, Claims, Expiration, and Mesalamine Patent Landscape

U.S. Patent No. 4,496,553 protected a treatment method using orally administered free 5-aminosalicylic acid, now known as mesalamine, formulated for site-specific release in the gastrointestinal tract. The patent issued January 29, 1985, and its original 17-year patent term expired January 29, 2002. It no longer creates an enforceable U.S. patent barrier for generic mesalamine products.

The claims were broad in therapeutic concept but dependent on several functional limitations: oral administration, free 5-aminosalicylic acid, a pharmaceutically acceptable carrier, controlled release, and delivery according to the actual disease site in an individual patient. The patent did not claim mesalamine as a chemical compound. It claimed a method of treating ulcerative colitis or Crohn's disease through site-directed oral delivery.

What does U.S. Patent 4,496,553 cover?

The patent covers oral treatment of ulcerative colitis or Crohn's disease using free 5-aminosalicylic acid in a formulation designed to release the drug at the location of disease in the patient's gastrointestinal tract. The claims are method claims rather than composition claims.

The two claims are materially similar:

Claim	Principal scope	Distinguishing language
1	Treatment of ulcerative colitis or Crohn's disease with free 5-ASA and a pharmaceutically acceptable carrier	Carrier controls release according to the disease site in an individual patient
2	Same treatment and active ingredient	Carrier must be orally administrable and control release according to the disease site

The patent therefore addresses the pharmacological and formulation problem created by administering 5-aminosalicylic acid orally. Unprotected 5-ASA can be absorbed or released before reaching the inflamed portion of the bowel. The claimed approach uses the carrier to control where the active ingredient becomes available.

The patent does not require a particular coating polymer, tablet structure, capsule, dosage strength, pH threshold, dissolution profile, or manufacturing process in the claims quoted. Those limitations may appear in the specification or prosecution history, but they are not express limitations of claims 1 and 2.

What are the key limitations of claims 1 and 2?

Free 5-aminosalicylic acid

The active ingredient must be free 5-aminosalicylic acid, commonly called mesalamine or mesalazine. This limitation distinguishes the claims from treatment with sulfasalazine, olsalazine, balsalazide, or another prodrug that releases 5-ASA after bacterial or chemical conversion.

A product containing mesalamine as the active pharmaceutical ingredient would satisfy the active-ingredient limitation more readily than a product that delivers a chemically linked 5-ASA derivative.

A composition consisting essentially of free 5-ASA and a carrier

The phrase "consisting essentially of" is narrower than "comprising" but broader than "consisting of." It generally permits inactive ingredients and other components that do not materially alter the basic and novel characteristics of the claimed formulation.

The basic and novel characteristic appears to be oral, site-directed delivery of free 5-ASA. A formulation containing conventional excipients, coatings, binders, lubricants, capsule materials, or release-control polymers would not necessarily fall outside the claim merely because those ingredients are present.

The phrase could become important if a formulation includes another active ingredient or a component that materially changes the treatment mechanism. A product containing mesalamine plus another therapeutic active may present a claim-construction issue, particularly if the additional active changes the basic and novel characteristics of the composition.

Controlled release

The carrier must control release of the effective amount of 5-ASA. Immediate-release oral mesalamine would face a stronger argument that it does not satisfy this limitation, although the issue would depend on the product's actual release behavior and the construction of "control the release."

The claims do not specify whether controlled release must mean:

Delayed release based on gastrointestinal pH;
Sustained release over time;
Colonic release;
Ileal release;
Release at a patient-specific anatomical location; or
A combination of time-controlled and location-controlled delivery.

The broad wording creates both potential reach and potential validity risk. A court would likely examine the specification, prosecution record, technical meaning of controlled release, and whether the asserted formulation actually directs delivery to the claimed disease site.

Delivery according to the actual site of disease

This is the most distinctive limitation. The formulation must be administered according to the actual site of ulcerative colitis or Crohn's disease in an individual patient.

The language suggests that the dosage form or regimen must be selected based on the location of disease. For example, a formulation intended to release in the colon could be selected for colonic disease, while a formulation releasing earlier in the intestinal tract could be selected for ileal or more proximal disease.

A generic mesalamine product would not automatically satisfy this limitation merely because it reaches the gastrointestinal tract. The claim requires a relationship between:

The patient's disease location;
The selected formulation or carrier; and
The controlled-release behavior of that formulation.

The phrase "actual site" may also create an indefiniteness and infringement issue. If a product is marketed for broad treatment of ulcerative colitis without selecting the formulation based on each patient's documented disease location, the patentee would need to establish how the individualized-location requirement is met.

How do claims 1 and 2 differ?

The practical difference is limited.

Claim 1 requires a pharmaceutically acceptable carrier that controls release and permits the effective amount of 5-ASA to be administered according to the disease site.

Claim 2 specifies that the carrier must be an orally administrable pharmaceutical carrier. Because both claims already require oral administration of the composition, claim 2's additional language may have limited narrowing effect. It clarifies that the carrier itself must be suitable for oral pharmaceutical use.

Issue	Claim 1	Claim 2
Treatment indication	Ulcerative colitis or Crohn's disease	Same
Active ingredient	Free 5-ASA	Free 5-ASA
Administration	Oral	Oral
Carrier	Pharmaceutically acceptable	Orally administrable pharmaceutical carrier
Release requirement	Controlled release according to disease site	Same
Patient-specific site language	Expressly included	Expressly included
Product-type limitation	Functional	Functional with more explicit oral-carrier language

Claim 2 may be viewed as a clarification or modest narrowing of claim 1 rather than a separate commercial invention.

When did U.S. Patent 4,496,553 expire?

U.S. Patent 4,496,553 issued January 29, 1985. Under the pre-Uruguay Round patent-term regime applicable to the patent, the term was generally 17 years from issuance. The resulting expiration date was January 29, 2002, absent an earlier terminal disclaimer or other term adjustment. The patent is expired and cannot be asserted against current U.S. products.

Event	Date
Patent issued	January 29, 1985
Original pre-1995 patent term	17 years from issue
Projected original expiration	January 29, 2002
Current enforceability	Expired

Patent term adjustment and patent term extension provisions created by later statutes generally do not convert an old, expired patent of this type into a currently enforceable drug patent. The patent is therefore relevant as historical prior art and as part of the origin of mesalamine delivery technology, but not as a current exclusivity asset.

What is the Orange Book status of U.S. Patent 4,496,553?

The patent was associated with the early patent estate for oral mesalamine products, including Asacol-type delayed-release products. Any historical Orange Book listing would have ceased to create a current patent bar when the patent expired.

The Orange Book distinguishes between a listed patent and an enforceable patent. A patent may appear in historical drug-product records while having no remaining enforceable term. Current generic applicants cannot be blocked by an expired patent, and a Paragraph IV certification against an expired patent does not create the same litigation exposure as a challenge to an unexpired listed patent.[2]

The commercial significance of the patent has therefore shifted:

Before 2002, it could support patent-based exclusivity for an eligible listed product.
After 2002, it became prior art and a historical formulation patent.
It does not currently prevent ANDA approval or generic launch.
Later, unexpired formulation or manufacturing patents may still affect a particular mesalamine product.

What products and formulations are related to the patent?

The patent's technical concept is reflected in several oral and rectal mesalamine delivery systems.

Oral delayed-release mesalamine

Examples include:

Asacol and successor products;
Delzicol delayed-release capsules;
Lialda or Mezavant MMX extended-release tablets;
Apriso extended-release capsules; and
Pentasa controlled-release capsules.

These products do not necessarily practice claims 1 and 2 in the same way. Their release mechanisms differ:

Product type	Typical delivery concept	Relevance to Patent 4,496,553
Delayed-release tablet or capsule	Delays release until a defined gastrointestinal environment	Strong conceptual overlap
pH-dependent release	Uses enteric polymer behavior to target distal intestine or colon	Potential functional overlap
Extended-release matrix	Releases mesalamine over an extended intestinal transit period	May overlap controlled-release language
Multi-matrix tablet	Distributes mesalamine through a prolonged release system	May implicate later formulation patents
Controlled-release granules	Releases drug from multiple coated particles	May implicate both the broad concept and later patents

A modern product may avoid infringement of later patents by using a different polymer, release profile, manufacturing method, or dosage form. It cannot avoid an expired patent's historical scope for current enforcement purposes.

Rectal mesalamine

Suppositories, enemas, and rectal suspensions deliver 5-ASA directly to the rectum or distal colon. They are less likely to implicate the oral-administration limitations of claims 1 and 2.

A rectal formulation may still reflect the patent's general treatment rationale, but claims 1 and 2 require oral administration. A nonoral product would ordinarily fall outside those claims.

How does the patent compare with later mesalamine patents?

U.S. Patent 4,496,553 is a foundational, functionally drafted patent. Later mesalamine patents generally pursued narrower and more technically defined protection.

Patent category	Typical claim focus	Relative strength compared with 4,496,553
Early treatment patent	Oral free 5-ASA delivered to the disease site	Broad concept, higher construction and validity risk
Enteric-coating patent	Specific polymers, coating weights, dissolution behavior, or pH release	Narrower but easier to test against a product
Extended-release patent	Matrix, multiparticulate, or multi-matrix delivery system	Product-specific and technically defined
Dosage-regimen patent	Dose, frequency, induction, or maintenance treatment	Narrower method scope
Manufacturing patent	Granulation, coating, compression, or capsule-filling process	Can create product-specific barriers
Combination patent	Mesalamine with another active or excipient system	Dependent on composition and treatment combination

Examples of later commercial patent estates include patents associated with Lialda's MMX delivery technology and patents associated with Apriso's extended-release formulation. These later patents were more likely to define specific release mechanisms than the broad site-specific concept in U.S. Patent 4,496,553.[3][4]

The key distinction is that a current generic manufacturer generally evaluates the later product-specific patents, not the expired foundational patent.

What patent litigation affected mesalamine products?

Mesalamine litigation has principally involved later formulation and product-specific patents rather than current enforcement of U.S. Patent 4,496,553. Generic applicants have challenged patents covering delayed-release coatings, extended-release systems, and MMX-type delivery platforms.

Historical litigation risk generally depended on four questions:

Whether the reference listed drug had an unexpired Orange Book patent;
Whether the ANDA applicant filed a Paragraph IV certification;
Whether the patent claims covered the generic's formulation or release profile; and
Whether the patent survived validity and infringement challenges.

The 1985 patent's expiration removed it from the current litigation stack. A generic applicant may still face litigation over an unexpired later patent even though the older patent has expired.

Are Paragraph IV challenges still relevant to this patent?

No. A Paragraph IV challenge to U.S. Patent 4,496,553 would have no current commercial effect because the patent expired in 2002.

Paragraph IV risk remains relevant to later mesalamine patents. An ANDA applicant may certify that a listed patent is invalid, unenforceable, or will not be infringed. The reference-product sponsor can file an infringement action within the statutory period, potentially triggering a 30-month stay under the Hatch-Waxman framework, subject to statutory exceptions and the status of the listed patent.[5]

For the expired patent itself:

No 30-month stay can provide meaningful protection from an expired patent.
No current launch injunction can be based solely on that patent.
No royalty-bearing license is needed solely to practice the expired claims.
The patent may still be cited as prior art against later patent applications.

What generic entry risks exist for mesalamine products?

The expired patent creates no standalone generic-entry barrier. Commercial risk depends on the product being copied.

For a basic oral mesalamine product

Risk is generally low from U.S. Patent 4,496,553 itself. The main issues are FDA approval requirements, bioequivalence, dissolution performance, labeling, manufacturing controls, and any later patents listed for the reference product.

For delayed-release products

Risk may arise from:

Enteric-coating composition;
Coating thickness or weight gain;
Dissolution at specified pH values;
Multiparticulate design;
Tablet matrix architecture;
Extended-release profile;
Capsule contents;
Specific excipient combinations; and
Manufacturing steps.

For MMX or other proprietary delivery platforms

Risk is higher if the generic duplicates the reference product's formulation architecture. A design-around may require a different matrix, coating, particle structure, or release mechanism while still meeting FDA performance requirements.

How strong is the patent estate for U.S. Patent 4,496,553?

As a current enforceable asset, the estate has no strength because the patent is expired. As historical intellectual property, the patent was significant because it claimed the therapeutic use of oral free 5-ASA in a site-controlled formulation before the modern mesalamine product market developed.

Its strengths when unexpired included:

Coverage of the therapeutic concept rather than one narrow polymer;
Coverage of both ulcerative colitis and Crohn's disease;
Coverage of orally administered free 5-ASA;
Functional coverage that could reach multiple formulation technologies; and
No express limitation to one dosage strength or one named product.

Its weaknesses included:

Ambiguity in "actual site" and "individual patient";
Lack of a precise release test in the claims;
Potential indefiniteness issues;
Potential written-description and enablement challenges for broad formulation coverage;
Difficulty proving individualized site selection in ordinary commercial prescribing; and
Potential prior-art issues involving 5-ASA, sulfasalazine, enteric delivery, and gastrointestinal targeting.

The broad functional drafting gave the patent conceptual reach but also created claim-construction and proof-of-infringement issues.

What manufacturing and intellectual-property barriers remain?

The expired patent does not prevent manufacture of mesalamine products. Current barriers are regulatory and technical rather than based on this patent.

A manufacturer must generally establish:

Pharmaceutical-grade mesalamine supply;
Impurity and degradation control;
Consistent particle size and polymorphic characteristics, where relevant;
Tablet or capsule content uniformity;
Coating uniformity;
Release performance across gastrointestinal pH conditions;
Stability;
Bioequivalence or an accepted alternative approval pathway; and
Compliance with current good manufacturing practice requirements.

Later patents may cover the coating, matrix, granulation, capsule, or manufacturing process. Trade secrets may also protect coating parameters, process controls, and scale-up methods even where no patent remains enforceable.

Does biosimilar risk apply to mesalamine?

No. Mesalamine is a chemically synthesized small-molecule drug, not a biologic. Biosimilar approval under the Public Health Service Act is not the relevant pathway.

Generic mesalamine products are generally approved through the ANDA pathway under the Federal Food, Drug, and Cosmetic Act. The relevant competitive issues are abbreviated new drug applications, therapeutic equivalence, bioequivalence, formulation patents, and Paragraph IV litigation, not biosimilar interchangeability.[5][6]

What is the commercial impact of the expired patent?

The patent's commercial value was concentrated in the period before expiration, when delayed-release oral mesalamine products were developing and branded products held market exclusivity. After January 29, 2002, the patent no longer supported a monopoly or royalty stream in the United States.

Revenue exposure today depends on later patents and the commercial product:

Commercial question	Effect of Patent 4,496,553
Can a generic sell free mesalamine?	Yes, subject to FDA approval and other valid rights
Can the patent block an ANDA?	No, because it is expired
Can it support a current infringement suit?	No
Can it affect later patent validity?	Yes, as prior art
Can a license be required?	No, not for the expired claims
Can later formulation patents matter?	Yes
Does it affect biologic competition?	No

Key Takeaways

U.S. Patent 4,496,553 claimed a method of treating ulcerative colitis or Crohn's disease with orally administered free 5-aminosalicylic acid.
The central limitation was controlled release at the actual site of disease in an individual patient.
Claims 1 and 2 are method claims, not composition claims.
The claims do not require a specific polymer, coating, dosage strength, tablet design, or dissolution profile.
The patent issued January 29, 1985, and expired January 29, 2002.
It is not a current U.S. Orange Book barrier to generic mesalamine entry.
Current patent risk lies primarily in later formulation, delivery-system, dosage-regimen, and manufacturing patents.
Mesalamine is a small molecule, so biosimilar analysis does not apply.
The patent's broad functional language created historical commercial reach but also potential indefiniteness, enablement, and infringement-proof issues.
No current license is required solely to practice the expired claims.

FAQs About U.S. Patent 4,496,553 and Mesalamine

Does U.S. Patent 4,496,553 cover all mesalamine products?

No. It covered a particular treatment method requiring oral administration, free 5-ASA, a release-controlling carrier, and administration according to the patient's disease site. It did not claim every mesalamine composition or every route of administration.

Does an immediate-release mesalamine tablet infringe the patent?

The claim would be difficult to apply to a genuinely immediate-release product because controlled release is an express limitation. The analysis would depend on the product's actual release behavior and the construction of the claim terms.

Does the patent cover rectal mesalamine enemas or suppositories?

Claims 1 and 2 require oral administration. Rectal enemas and suppositories would generally fall outside those specific claims.

Can a company obtain a license to practice this expired patent?

A license is not required to practice an expired U.S. patent. Parties may document historical rights or obtain rights in related foreign or later patents, but U.S. Patent 4,496,553 itself no longer supplies enforceable exclusivity.

Could the patent still invalidate a later mesalamine patent?

Yes. Its disclosure may be prior art against later patent claims, subject to the applicable prior-art rules, effective filing dates, priority claims, and the specific subject matter disclosed or enabled by the patent.

References

U.S. Patent No. 4,496,553. (1985). Treatment of inflammatory bowel diseases. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Patent No. 6,773,720. (2004). Controlled release compositions containing 5-aminosalicylic acid. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs. Center for Drug Evaluation and Research.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
Public Health Service Act, 42 U.S.C. § 262.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Denmark	1202/80	Mar 20, 1980

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Japan	S57500432	⤷ Start Trial
World Intellectual Property Organization (WIPO)	8102671	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,496,553

Summary for Patent: 4,496,553