United States Patent 6,551,620: Mesalamine Pellet Formulation Scope, Expiration, and Patent Landscape

U.S. Patent No. 6,551,620 protects a controlled-release pellet formulation containing aminosalicylic acid, principally 5-aminosalicylic acid, also known as mesalamine or mesalazine. The core must contain a non-gel-forming, water-permeable polymer matrix based on specified ethyl acrylate and methyl methacrylate polymers, or a related trimethylammonioethyl methacrylate chloride copolymer. The pellets must also have an enteric coating.

The patent’s key commercial concept is a multiparticulate mesalamine dosage form that resists release in gastric acid and releases the active ingredient progressively in the intestinal tract. The patent term has expired, so the issued claims no longer block commercial manufacture or sale in the United States. The formulation architecture remains relevant for freedom-to-operate analysis because later patents may protect specific products, coating systems, manufacturing processes, or release profiles.

What does U.S. Patent 6,551,620 protect?

The patent protects a combination of structural and functional limitations rather than mesalamine generally. Independent claim 1 requires all of the following:

Required element	Scope
Dosage form	Orally administrable pharmaceutical pellet formulation
Therapeutic location	Controlled release for the intestinal tract
Pellet structure	Core plus enteric coating
Active ingredient	Aminosalicylic acid or a pharmaceutically acceptable salt
Core matrix	Non-gel-forming polymer matrix
Polymer behavior	Essentially insoluble in the intestinal tract and permeable to intestinal fluids and active compound
Minimum polymer amount	At least 1% by weight of the core
Permitted matrix polymers	Poly(ethyl acrylate, methyl methacrylate), or poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride)

The claim does not cover every mesalamine tablet, capsule, granule, or enteric-coated dosage form. A competing product must practice the claimed pellet-core architecture to fall within literal claim 1.

The principal matrix polymers correspond to pharmaceutical acrylic polymers marketed under Eudragit designations. The ethyl acrylate/methyl methacrylate copolymer is associated with Eudragit NE-type neutral, water-permeable polymers. The trimethylammonioethyl methacrylate chloride-containing copolymers are associated with Eudragit RL or RS-type polymers, depending on quaternary ammonium content and commercial grade.

How do the dependent claims narrow the patent scope?

Claims 2 through 9 impose additional formulation or dissolution limitations.

Polymer concentration

Claim 2 limits the matrix-forming polymer to 4% to 10% by weight of the core. This range is narrower than the 1% minimum in claim 1 and may correspond to the commercially useful release window identified in the patent.

A product with 3% matrix polymer could potentially fall within claim 1 but not claim 2. A product with 4% to 10% polymer would need to satisfy the remaining limitations of claim 1 as well.

Homogeneous matrix structure

Claim 3 requires the polymer matrix to extend through the entire core and requires homogeneous dispersion of the active compound. This limitation distinguishes a true matrix pellet from a layered pellet in which mesalamine is deposited on an inert seed and subsequently coated with a polymer film.

The distinction matters in product comparisons. A product can use the same polymer family but avoid claim 3 if the polymer is limited to a surface layer and does not form the entire core.

Active ingredient

Claim 4 specifies 5-aminosalicylic acid, the active ingredient commonly called mesalamine in the United States and mesalazine in many other markets.

The claim does not require a particular mesalamine particle size, polymorph, salt, dosage strength, or daily dose beyond the limitations inherited from claim 1.

Enteric coating

Claims 5 and 6 require an enteric coating based on a methacrylic acid copolymer or methylhydroxypropyl-cellulose phthalate. Claim 6 narrows the coating to a poly(methacrylic acid, methyl methacrylate) copolymer containing free carboxyl groups.

The specified 1:1 and 1:2 methacrylic acid-to-methyl methacrylate ratios in claim 8 correspond broadly to pH-dependent methacrylic acid copolymers used to delay release until the dosage form reaches the intestine.

Single coating layer

Claim 7 requires only one coating layer. This limitation can be important in design-around analysis. A formulation with a subcoat, seal coat, intermediate barrier coat, or multiple enteric layers may raise questions about literal infringement of claim 7, although it could still fall within claim 1 or another claim that does not require one coating layer.

Specific formulation combination

Claim 8 covers a formulation combining:

5-aminosalicylic acid;
a poly(ethyl acrylate, methyl methacrylate) 2:1 matrix;
an enteric coating using a poly(methacrylic acid, methyl methacrylate) 1:1 or 1:2 copolymer; and
optional pharmaceutical additives.

Claim 8 is narrower than claim 1 but commercially significant because it identifies a defined combination of neutral acrylic matrix polymer and acid-functional enteric polymer.

Dissolution profile

Claim 9 requires a specific release profile:

Test condition	Required release
0.1 M hydrochloric acid after 2 hours	Less than 10%
Artificial gastric juice at approximately pH 6.8 after 30 minutes	10% to 30%
Same medium after 2 hours	40% to 60%
Same medium after 6 hours	At least 80%

This limitation is potentially difficult to assess without reproducing the specified dissolution method. Release depends on apparatus, agitation, temperature, media composition, pellet size distribution, coating weight, assay method, and sampling correction.

A product with the same ingredients may not meet claim 9 if its release curve falls outside any specified interval. Conversely, a product that uses different excipients may still meet the dissolution limitations if it satisfies the structural limitations of the relevant claim.

What dosage forms and methods of treatment are covered?

Claims 10 and 11 extend the composition claims to pharmaceutical formulations containing the pellets, including capsules and tablets.

These claims do not independently protect capsules or tablets containing arbitrary mesalamine pellets. The incorporated pellets must meet claim 1 and any additional limitations of the applicable dependent claim.

Claims 12 through 17 are method claims. They cover administration of the claimed pellet formulation for:

intestinal disorders;
secondary disorders resulting from intestinal disease;
intestinal cancer;
inflammatory intestinal disorders in active or remission phases;
gastrointestinal polyps;
adenomas or polypous growth;
reduction of adenoma or colorectal polyp recurrence; and
colon cancer.

The method claims inherit the formulation requirements of claim 1. Administration of a mesalamine product that does not contain the claimed pellet structure would not satisfy these claims.

The cancer and polyp indications are broader than the principal modern regulatory indications for mesalamine products. Their presence in the patent does not establish FDA approval for those uses.

When did U.S. Patent 6,551,620 expire?

U.S. Patent No. 6,551,620 issued on April 22, 2003. Its term was governed by the patent-term rules applicable to the relevant application and priority filings. The patent is expired and cannot currently provide enforceable exclusionary rights in the United States. The USPTO patent record and public patent databases identify the patent as expired based on its statutory term.[1]

The expiration has several consequences:

The issued claims no longer prevent a third party from practicing the claimed pellet formulation.
A generic or branded competitor does not need a Paragraph IV certification directed solely to this expired patent.
Any patent-term extension or pediatric exclusivity must be checked separately, although no currently enforceable term for this patent should be assumed from the patent document alone.
Later patents may still create barriers involving specific commercial formulations or manufacturing processes.

Patent expiration does not eliminate regulatory exclusivity, trade-secret protection, data rights, or later-issued patents.

What is the Orange Book status of U.S. Patent 6,551,620?

U.S. Patent 6,551,620 should not be treated as a currently blocking Orange Book patent. The FDA Orange Book lists patents submitted by applicants for approved drug products, but listing status is product-specific and does not revive an expired patent.[2]

For mesalamine products, Orange Book analysis must be conducted product by product. Relevant products have included:

Product	Active ingredient	Dosage technology	Commercial sponsor or historical sponsor
Asacol and Delzicol	Mesalamine	Delayed-release tablets or capsules	Various legacy sponsors, including Warner Chilcott and Allergan
Asacol HD	Mesalamine	Delayed-release tablets	Warner Chilcott and successors
Lialda	Mesalamine	MMX multimatrix delayed-release tablets	Shire and successors
Apriso	Mesalamine	Extended-release capsules	Salix and successors
Pentasa	Mesalamine	Controlled-release capsules	Ferring
Salofalk	Mesalamine	Enteric-coated tablets, granules, or related multiparticulates	Dr. Falk Pharma

The products do not share a single patent estate. Their patents can cover matrix systems, coating compositions, tablet architecture, release profiles, dosing regimens, manufacturing methods, or specific combinations of excipients.

Which companies have challenged mesalamine patents?

Mesalamine products have generated multiple generic-drug challenges, but challenges to other products should not be attributed automatically to U.S. Patent 6,551,620.

The principal competitive groups have included:

generic pharmaceutical manufacturers seeking approval for delayed-release or extended-release mesalamine products;
branded sponsors of Asacol, Delzicol, Lialda, Apriso, and Pentasa;
specialty gastrointestinal companies such as Salix;
Dr. Falk Pharma in relation to Salofalk and related mesalamine formulations;
manufacturers developing alternative multiparticulate, matrix, MMX, or pH-dependent release systems.

A Paragraph IV certification is directed to patents listed for a specific reference-listed drug. Because U.S. Patent 6,551,620 is expired, a current ANDA applicant would focus on unexpired patents listed for the relevant reference product, not on this patent.

How does this patent compare with competing mesalamine patent estates?

The patent is narrower than broad product patents covering mesalamine itself but more technically specific than a conventional enteric-coating patent.

Estate type	Typical protected subject matter	Relationship to U.S. 6,551,620
Active ingredient patents	Mesalamine compound or salt	U.S. 6,551,620 does not claim mesalamine alone
Conventional enteric coating patents	pH-dependent release coatings	The patent requires an enteric-coated pellet plus a specified matrix core
Matrix patents	Drug dispersed in insoluble permeable polymer	Closest technical category
MMX patents	Hydrophilic and lipophilic multimatrix tablets	Usually distinct from the claimed pellet matrix
Multiparticulate patents	Pellets, granules, beads, or coated particles	Potential overlap depends on core and coating limitations
Method-of-use patents	Specific dosing schedules or disease indications	Claims 12 to 17 provide broad use limitations but are expired
Manufacturing patents	Fluid-bed coating, extrusion, layering, curing, or pelletization	May remain relevant after expiration of the composition patent

The strongest historical feature of the patent was the combination of a neutral, non-gel-forming matrix with an enteric coating. The patent did not rely only on pH-triggered coating dissolution. It also required controlled diffusion from the underlying matrix.

What manufacturing and intellectual-property barriers remain?

The expired patent removes one barrier but does not eliminate all development risks. A current product may still encounter:

Formulation patents

Later patents may claim:

a specific acrylic polymer ratio;
a defined coating weight gain;
a particular pellet diameter;
a combination of immediate-release and delayed-release fractions;
a multi-unit capsule;
a specific excipient system;
a defined dissolution profile;
a manufacturing cure or drying step.

Process patents

Potentially relevant process claims may cover:

extrusion-spheronization;
powder layering onto starter cores;
fluid-bed coating;
aqueous polymer dispersions;
curing temperature and duration;
control of residual solvent;
coating uniformity;
pellet separation and capsule filling.

Regulatory barriers

FDA approval requires demonstration of pharmaceutical equivalence and bioequivalence or another accepted approval pathway. Differences in release mechanism can create development and regulatory issues even where the expired patent no longer applies.

Trade secrets

Coating suspension preparation, polymer dispersion handling, pellet size control, curing conditions, and dissolution-targeting methods may remain protected as confidential know-how even after patent expiration.

What generic launch scenarios exist for this formulation?

The most straightforward launch scenario is a mesalamine multiparticulate product that practices the expired patent’s formulation concept while avoiding unexpired product-specific patents.

Three technical approaches are common:

Direct practice of the expired architecture. A sponsor uses 5-aminosalicylic acid in an acrylic matrix with an enteric coating.
Matrix redesign. A sponsor uses a different insoluble permeable polymer or a different matrix concentration.
Dosage-form redesign. A sponsor uses an MMX tablet, coated granule, osmotic system, or another release platform.

The primary current risk is therefore not U.S. Patent 6,551,620 itself. It is the possibility that a proposed product reads on later patents covering a branded reference product, a specific release profile, or a manufacturing process.

How strong was the patent estate?

The patent was technically focused and commercially relevant for products using the claimed pellet architecture. Its strongest limitations were the required polymer classes, matrix structure, enteric coating, and dissolution profile. Its weaknesses were the narrow dependence on a particular multiparticulate design and the eventual expiration of the patent term.

Claim 1 had meaningful breadth within the defined architecture because it covered either a neutral ethyl acrylate/methyl methacrylate polymer or a related quaternary ammonium methacrylate polymer. Claims 2 through 9 narrowed the protection through concentration, homogeneity, coating chemistry, layer count, formulation ratios, and dissolution performance.

The claims would have required detailed product testing. Ingredient-list review alone would not establish infringement or non-infringement because several limitations concern polymer function, distribution throughout the core, and dissolution behavior.

Key Takeaways

U.S. Patent 6,551,620 covers an enteric-coated mesalamine pellet with a non-gel-forming acrylic polymer matrix.
Claim 1 requires a core, enteric coating, aminosalicylic acid, a specified insoluble permeable matrix, and at least 1% matrix polymer.
The patent’s central commercial concept is a controlled-release multiparticulate dosage form for intestinal delivery.
Claims 8 and 9 provide the most formulation-specific protection through polymer ratios and dissolution criteria.
Claims 10 and 11 cover capsules and tablets containing the claimed pellets.
Claims 12 through 17 cover treatment of intestinal disorders, polyps, and colon cancer using the claimed formulation.
The patent has expired and is not a current standalone barrier to U.S. commercial entry.
Current mesalamine freedom-to-operate analysis must focus on later patents listed for the relevant reference-listed drug, formulation patents, process patents, and regulatory requirements.
An expired patent may remain important as prior art and as a technical map of the formulation space, but it does not support a current infringement action.

FAQs About U.S. Patent 6,551,620

Does U.S. Patent 6,551,620 cover all mesalamine products?

No. It covers a particular pellet formulation with a specified acrylic polymer matrix and enteric coating. Mesalamine tablets, capsules, granules, and MMX products may fall outside its claim limitations.

Can a company launch a mesalamine pellet product without addressing this patent?

Yes, because the patent has expired. The company must still evaluate later patents, FDA requirements, manufacturing patents, and product-specific Orange Book listings.

Is Eudragit NE covered by the patent?

A poly(ethyl acrylate, methyl methacrylate) matrix is within the polymer language of claim 1. Whether a particular commercial Eudragit grade satisfies every claim limitation requires analysis of its composition, function, use in the core, and the resulting dosage form.

Does an enteric-coated mesalamine capsule infringe automatically?

No. The capsule must contain pellets meeting the applicable claim limitations. A capsule containing a different type of granule, tablet, matrix, or coated particle may not satisfy the claims.

Are the colon-cancer method claims commercially significant today?

They are part of the issued claim set, but the patent has expired. Their presence does not establish current FDA approval of mesalamine for colon-cancer treatment or prevention.

References

United States Patent and Trademark Office. (2003). U.S. Patent No. 6,551,620, Pharmaceutical formulation.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs.
DailyMed. (2024). Mesalamine delayed-release and extended-release product labeling. National Library of Medicine.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	241964	⤷ Start Trial
Canada	2297832	⤷ Start Trial
Germany	19732903	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,551,620

Summary for Patent: 6,551,620