United States Patent 4,559,330: Olsalazine Scope, Claims, Expiration and Patent Landscape

U.S. Patent No. 4,559,330 covers the use of 3,3'-azo-bis-(6-hydroxybenzoic acid), commonly known as olsalazine, and its pharmaceutically acceptable salts for inflammatory intestinal disease, particularly ulcerative colitis. The patent also covers oral pharmaceutical compositions, treatment doses of 0.5 to 10 grams per day, and the disodium salt.

The patent issued in 1985 under the pre-1995 U.S. patent-term regime and expired in December 2002, assuming no terminal disclaimer, reexamination adjustment, or other unusual term modification. It therefore does not create a current U.S. exclusionary right. Its commercial importance is historical: it established the original method-of-use and composition protection for olsalazine, later marketed as Dipentum.

What compound does U.S. Patent 4,559,330 protect?

The patent protects 3,3'-azo-bis-(6-hydroxybenzoic acid), including pharmaceutically acceptable salts. The clinically relevant salt is olsalazine sodium, also called disodium olsalazine.

Item	Description
Chemical substance	3,3'-azo-bis-(6-hydroxybenzoic acid)
Common name	Olsalazine
Commercial salt	Olsalazine sodium or disodium olsalazine
Therapeutic area	Inflammatory bowel disease
Principal indication	Ulcerative colitis
Dosage form associated with product	Oral delayed-release capsules
Development rationale	Colonic delivery of 5-aminosalicylic acid
U.S. patent	U.S. 4,559,330
Issue date	December 24, 1985
Pre-1995 patent term	Generally 17 years from issue
Estimated expiration	December 24, 2002

Olsalazine contains two 5-aminosalicylic-acid-like aromatic units joined by an azo linkage. Colonic bacteria cleave the azo bond, releasing 5-aminosalicylic acid in the large intestine. This mechanism distinguishes olsalazine from systemically absorbed formulations that deliver 5-aminosalicylic acid through other release technologies.[1][2]

What do the claims of U.S. Patent 4,559,330 cover?

The claims divide into four principal groups:

Broad therapeutic methods for inflammatory intestinal disease.
Narrower methods for ulcerative colitis.
Pharmaceutical compositions containing olsalazine or its salts.
Oral treatment and dose limitations, including disodium olsalazine.

How broad is claim 1?

Claim 1 covers:

A method of treating inflammatory intestinal diseases by administering a therapeutically effective amount of olsalazine or a pharmaceutically acceptable salt.

The claim has four material limitations:

A patient must have an inflammatory intestinal disease.
Olsalazine or a pharmaceutically acceptable salt must be administered.
The administered amount must be therapeutically effective.
The conduct must be treatment of the disease, rather than merely administration for research or another purpose.

The phrase “inflammatory intestinal diseases” is broader than ulcerative colitis. It can encompass inflammatory conditions affecting the intestine, including disease involving the colon. The specification and dependent claims are important for determining how far the term extends. A court would likely construe the claim in light of the patent’s disclosure, examples, medical terminology at the filing date, and the specific emphasis on ulcerative colitis and large-intestine delivery.

Claim 1 does not require oral administration. Parenteral, rectal, or other routes could theoretically fall within its language if the accused administration is medically effective and otherwise supported by the patent disclosure. Claims 2, 4, and 8 narrow the protection to oral administration or oral compositions.

How narrow are claims 3 and 4?

Claim 3 is limited to treating ulcerative colitis. It requires administration of olsalazine or a pharmaceutically acceptable salt in a therapeutically effective amount.

Claim 4 narrows claim 3 to oral administration.

These are method-of-use claims. They do not require a specific capsule, excipient, release profile, tablet coating, manufacturing process, or dose unless those limitations are imported from a dependent claim.

The claim language uses “ulcerous colitis,” while modern regulatory materials generally use “ulcerative colitis.” The terminology difference should not, by itself, materially alter the intended disease scope.

What formulations are protected by U.S. Patent 4,559,330?

Claims 5 through 8 cover compositions containing olsalazine or a pharmaceutically acceptable salt together with at least one pharmaceutically acceptable carrier or adjuvant.

Claim	Principal scope
5	Pharmaceutical composition containing olsalazine or a salt plus carrier or adjuvant
6	Composition for treating inflammatory intestinal disease
7	Composition for treating ulcerative colitis
8	Oral composition for treating inflammatory disease in the large intestine

These composition claims are structurally broad. They do not expressly require:

A capsule;
A delayed-release coating;
A particular excipient;
A specific particle size;
A defined dissolution profile;
A specific olsalazine concentration;
A particular manufacturing process; or
A defined release location.

A generic product containing olsalazine sodium could have implicated these claims during the patent term even if it used different excipients or a different capsule supplier. The principal defense would have involved noninfringement, invalidity, or a showing that the product did not meet a claim limitation.

Does the patent cover delayed-release or enteric-coated formulations?

The claims supplied do not expressly require delayed release or enteric coating. The patent therefore appears to cover a wider class of pharmaceutical compositions than a claim limited to a particular colon-targeted delivery system.

That does not mean every formulation containing olsalazine would necessarily infringe. The composition must still satisfy the claim’s requirement for olsalazine or an acceptable salt combined with a pharmaceutically acceptable carrier or adjuvant. A formulation containing only an impurity, metabolite, or chemically distinct derivative would fall outside the literal compound limitation.

What dose range does the patent claim?

Claims 9 and 10 specify a therapeutically effective adult dose of 0.5 to 10 grams per day.

This range is broad. It covers a 20-fold span and could include clinically used doses of olsalazine sodium, depending on whether the dose is measured as olsalazine free acid, the disodium salt, or product weight.

Dose claims are generally narrower than the independent method claims. A treatment falling outside the claimed range could avoid literal infringement of claims 9 and 10 while still potentially implicating claims 1 or 3 if all limitations of those claims were met.

The dose limitation does not appear to require:

A particular dosing frequency;
A specific dose per capsule;
A fixed treatment duration;
A loading dose;
A maintenance dose; or
Administration with food.

How does the disodium salt limitation affect scope?

Claim 12 limits the method claims to the disodium salt. Claim 13 is intended to limit the composition claims to the disodium salt, although the wording supplied appears to contain a dependency or drafting defect because it refers to “claims 5-8 and 9,” while claim 9 is a method claim.

The practical significance is limited today because the patent has expired. During the patent term, a product using disodium olsalazine would have presented a direct infringement risk under the salt-specific claims, while another pharmaceutically acceptable salt could have implicated the broader claims.

A court would likely analyze whether “disodium salt” means the fully neutralized disodium form or whether the term could include hydrates, solvates, polymorphs, or mixtures. The answer would depend on the specification and prosecution history. A routine solid-state variation would not ordinarily avoid a claim directed to the chemical salt if the claimed molecular form remains present.

When did U.S. Patent 4,559,330 lose exclusivity?

The patent’s ordinary term expired in December 2002.

Milestone	Date or status
Priority and development period	Early 1980s
U.S. application period	Early 1980s
Patent issued	December 24, 1985
Ordinary pre-1995 term	17 years from issue
Estimated expiration	December 24, 2002
Current enforceability	Expired
Current Paragraph IV relevance	None for this patent
Current biosimilar relevance	None

Because the patent issued before June 8, 1995, the applicable term was generally 17 years from issuance rather than 20 years from the earliest effective U.S. nonprovisional filing date.[3] A complete term opinion would review the face of the patent, maintenance-fee records, terminal disclaimers, reexamination certificates, and any patent-term adjustment or extension records. The standard public term calculation places expiration in 2002.

What is the FDA regulatory status of olsalazine?

Olsalazine sodium was approved by the FDA as Dipentum for the maintenance of remission in adults with ulcerative colitis. The product is administered orally and was developed to deliver active 5-aminosalicylic acid to the colon through bacterial cleavage of the azo bond.[1]

Regulatory issue	Status
Active ingredient	Olsalazine sodium
Brand	Dipentum
FDA pathway	New drug approval
Main indication	Maintenance of remission of ulcerative colitis
Administration	Oral
Regulatory category	Small-molecule prescription drug
Biosimilar pathway	Not applicable
Generic pathway	Abbreviated New Drug Application pathway potentially applicable

The patent’s broad treatment claims extend beyond the approved maintenance indication. FDA approval therefore does not define the full patent scope. Conversely, approval of an indication does not establish that every patent claim covering that indication remains enforceable.

What is the Orange Book status of olsalazine?

The Orange Book is relevant because olsalazine is a small-molecule drug approved under the Federal Food, Drug, and Cosmetic Act. It is not a biologic and does not use the biosimilar framework.

Patent listings in the Orange Book are product- and NDA-specific. The expiration of U.S. 4,559,330 removes that patent as a current barrier to an ANDA applicant. Any present-day exclusivity analysis must distinguish between:

Expired patents;
Current patents listed for the approved product, if any;
Regulatory exclusivity;
Drug-supply or manufacturing constraints; and
Commercial viability of the generic market.

The original olsalazine patent should not be treated as a live Orange Book barrier. A current applicant would focus on any later-listed formulation, polymorph, process, or use patents and on the regulatory status of the reference-listed drug.

Were there Paragraph IV challenges or litigation?

A Paragraph IV certification against U.S. 4,559,330 would have been relevant only before its expiration. After expiration, an applicant would not need to challenge the patent to obtain approval because the patent no longer blocks commercial entry.

The available claim and patent information does not establish a specific Paragraph IV notice, district-court complaint, settlement agreement, or appellate decision involving this patent. No litigation event should be attributed to U.S. 4,559,330 without a matching record in PACER, USPTO records, FDA correspondence, or a reported judicial opinion.

The main legal risk during the active term would have been ordinary infringement litigation against an ANDA applicant or commercial manufacturer. The main defenses would have included:

Invalidity for anticipation or obviousness;
Lack of enablement or written description;
Noninfringement based on the administered compound or formulation;
Failure to meet the inflammatory-disease or ulcerative-colitis limitation;
Dose outside the claimed range; and
Nonuse of the claimed salt.

How strong was the patent estate?

Compound and method-of-use strength

The patent had strong coverage for the specific molecule and its salts because the independent claims identified olsalazine directly. A competitor could not avoid the core claims merely by changing the tablet excipient or capsule supplier.

The method claims were broader than the approved label in some respects. Claim 1 addressed inflammatory intestinal diseases generally, while claim 3 focused on ulcerative colitis. That breadth increased historical coverage but also created potential validity and claim-construction issues.

Formulation strength

The formulation claims were broad but technically less differentiated. They required olsalazine, a carrier or adjuvant, and in some claims an oral or disease-treatment context. They did not appear to claim a detailed delayed-release architecture.

A later patent directed specifically to enteric coating, controlled release, particle engineering, capsule design, or manufacturing could have provided a separate layer of protection. The supplied claims do not establish such later rights.

Manufacturing and IP barriers

Olsalazine’s synthesis, purification, salt formation, and dosage-form manufacture may create practical barriers even after patent expiry. Those are commercial and regulatory barriers, not continuing exclusivity under U.S. 4,559,330.

Potential technical issues include:

Control of azo-compound impurities;
Reproducible disodium salt formation;
Stability in the finished dosage form;
Dissolution and release performance;
Capsule fill uniformity;
Microbial or chemical degradation; and
Demonstration of pharmaceutical equivalence for an ANDA.

How does olsalazine compare with other ulcerative-colitis drugs?

Drug or product	Active approach	Patent-risk profile
Olsalazine	Azo-linked 5-ASA precursor cleaved in the colon	Original composition and use patent expired
Sulfasalazine	Sulfapyridine linked to 5-ASA	Separate compound and use patent history
Mesalamine delayed-release products	Direct 5-ASA with pH-dependent or controlled release	Product-specific formulation and method patents
Balsalazide	5-ASA prodrug with carrier group	Separate composition, formulation, and use patent landscape
Biologic therapies	Antibodies or other biologic agents	Biosimilar and biologic-exclusivity framework applies

Olsalazine’s historical patent advantage was molecule-level protection combined with broad disease-treatment claims. Its commercial disadvantage is tolerability, particularly dose-related diarrhea, and the availability of alternative 5-ASA formulations.[1][2]

What generic launch risks exist today?

The expired patent does not block generic launch. Current risks are more likely to arise from:

FDA approval and pharmaceutical-equivalence requirements;
Reference-product availability;
Low market volume;
Manufacturing economics;
Product discontinuation or shortage status;
Any later patents listed for the reference product;
Labeling and indication strategy; and
Commercial competition from mesalamine and other ulcerative-colitis treatments.

A generic olsalazine applicant would generally assess the ANDA pathway, Orange Book listings, bioequivalence expectations, and product-specific chemistry and manufacturing controls. The expired 1985 patent would be relevant as prior art and historical context, not as an enforceable barrier.

Key Takeaways

U.S. 4,559,330 covers olsalazine and pharmaceutically acceptable salts, including disodium olsalazine.
The patent claims treatment of inflammatory intestinal disease and ulcerative colitis.
It includes oral administration, oral compositions, large-intestine treatment, and a 0.5-to-10-gram daily adult dose range.
The composition claims are broad and do not expressly require a specific delayed-release coating or capsule design.
The patent issued on December 24, 1985, and its ordinary term expired in December 2002.
It is not a current Paragraph IV barrier and has no biosimilar relevance.
Current commercial risk depends on later patents, FDA requirements, manufacturing economics, and market demand rather than U.S. 4,559,330.
The principal approved product associated with olsalazine is Dipentum, indicated for maintenance of remission in adult ulcerative colitis.

FAQs About U.S. Patent 4,559,330 and Olsalazine

Does U.S. Patent 4,559,330 cover Dipentum?

Yes. The patent covers the active pharmaceutical ingredient used in Dipentum, olsalazine sodium, along with methods and compositions involving that compound. The patent itself expired in 2002.

Can a company now sell olsalazine sodium without licensing the patent?

The expired patent does not require a license for current U.S. commercialization. A company must still satisfy FDA approval, manufacturing, labeling, and other applicable regulatory requirements.

Is olsalazine a biologic subject to biosimilar competition?

No. Olsalazine is a chemically synthesized small molecule. Generic competition proceeds through the ANDA framework rather than the biosimilar pathway.

Did the patent claim mesalamine products?

No. The claims identify 3,3'-azo-bis-(6-hydroxybenzoic acid) and its salts. Mesalamine is a separate active ingredient and requires a separate patent and regulatory analysis.

Does the patent cover treatment of Crohn's disease?

Claim 1 uses the broad phrase “inflammatory intestinal diseases,” but the ultimate scope would depend on claim construction, the specification, and the evidentiary record. The patent expressly narrows other claims to ulcerative colitis and large-intestine disease. Because the patent expired, this question has no current infringement consequence under U.S. 4,559,330.

References

U.S. Food and Drug Administration. (n.d.). Dipentum (olsalazine sodium) prescribing information. FDA.
National Library of Medicine. (n.d.). Olsalazine. DailyMed. U.S. National Library of Medicine.
United States Patent and Trademark Office. (1985). U.S. Patent No. 4,559,330: 3,3'-Azo-bis-(6-hydroxybenzoic acid) and pharmaceutical compositions containing it. U.S. Department of Commerce.
United States Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, patent term and expiration provisions. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	8002322	Mar 26, 1980

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	549237	⤷ Start Trial
Australia	6862481	⤷ Start Trial
Canada	1179602	⤷ Start Trial
Germany	3161216	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,559,330

Summary for Patent: 4,559,330