United States Drug Patent 4,859,660: Scope, Claims, Expiration, and Ursodeoxycholic Acid Patent Landscape

U.S. Patent No. 4,859,660 protects a method of treating primary biliary cirrhosis, now commonly called primary biliary cholangitis, with ursodeoxycholic acid, or UDCA. Its dependent claims narrow the method by specifying a daily dose of 13 to 15 mg/kg, oral administration, and gelatin capsules. The patent does not claim UDCA itself, a particular chemical formulation, a manufacturing process, or a composition of matter.

The patent issued on August 22, 1989. Because it was a pre-1995 U.S. patent, its ordinary term was 17 years from issuance. On that basis, U.S. Patent No. 4,859,660 expired on August 22, 2006, absent a term adjustment, extension, or other unusual prosecution event. The patent therefore does not create a current barrier to generic ursodiol use for primary biliary cholangitis. [1][2]

What does U.S. Patent 4,859,660 claim?

The patent claims a therapeutic method rather than a product.

Claim	Subject matter	Scope
1	Treating primary biliary cirrhosis with an effective amount of UDCA	Broadest independent claim
2	Claim 1 with 13 to 15 mg/kg/day of UDCA	Dose-limited method
3	Claim 1 with oral administration	Route-limited method
4	Claim 3 with gelatin capsules	Dosage-form-limited method

The claim hierarchy is cumulative. Claim 2 requires every limitation of claim 1 plus the specified dose. Claim 3 requires claim 1 plus oral administration. Claim 4 requires claim 3 plus oral administration in gelatin capsules.

Claim 1: treatment of primary biliary cirrhosis

Claim 1 requires:

A patient suffering from primary biliary cirrhosis;
Administration of ursodeoxycholic acid; and
An amount that is effective to treat the disease.

The claim does not specify a particular tablet, capsule strength, excipient, manufacturing process, treatment duration, biochemical endpoint, or clinical response threshold. The central limitation is the disease indication combined with administration of UDCA.

The claim is narrower than a claim covering UDCA for all liver diseases. It is also narrower than a claim covering UDCA as a general pharmaceutical product. A product containing UDCA would not, by itself, infringe claim 1. The relevant conduct would be use of that product to treat primary biliary cirrhosis.

Claim 2: 13 to 15 mg/kg/day

Claim 2 narrows the claimed method to a daily dose between 13 and 15 mg/kg. A regimen outside that range would not literally satisfy claim 2, although it could still fall within claim 1 if the dose is an effective amount.

The range is weight-based and expressed per day. A dosing schedule must therefore be evaluated by the total daily amount administered relative to patient body weight. For a 70-kilogram patient, the claimed range corresponds to approximately 910 to 1,050 mg per day.

Patient weight	13 mg/kg/day	15 mg/kg/day
50 kg	650 mg/day	750 mg/day
60 kg	780 mg/day	900 mg/day
70 kg	910 mg/day	1,050 mg/day
80 kg	1,040 mg/day	1,200 mg/day
90 kg	1,170 mg/day	1,350 mg/day

A fixed 1,000-mg daily dose could fall inside or outside claim 2 depending on the patient’s weight. For example, it is within the claimed range for a patient weighing approximately 66.7 to 76.9 kilograms.

Claim 3: oral administration

Claim 3 narrows claim 1 by requiring oral administration. Intravenous, intramuscular, rectal, or other nonoral administration would not literally meet this limitation.

The claim does not require a particular oral dosage form. Tablets, capsules, suspensions, powders, and other orally administered products could satisfy the oral-route limitation if the other elements of claim 1 are met.

Claim 4: gelatin capsules

Claim 4 adds two requirements to claim 1:

Oral administration; and
Administration in gelatin capsules.

The claim does not expressly require hard-shell capsules, soft-gel capsules, a particular capsule fill, a specific UDCA concentration, or a named commercial product. A capsule made with gelatin could fall within the claim if used orally to treat primary biliary cirrhosis.

A vegetarian capsule made from hydroxypropyl methylcellulose would present a stronger noninfringement position against the literal “gelatin capsules” limitation. That conclusion would depend on the patent’s claim construction and the physical characteristics of the product.

What does U.S. Patent 4,859,660 not protect?

The patent does not claim the following subject matter:

UDCA as a chemical compound;
A composition of matter containing UDCA;
A particular crystalline or polymorphic form of UDCA;
A tablet formulation;
A soft-gel formulation as such;
A specific capsule fill or excipient system;
A manufacturing process for UDCA;
A method of synthesizing or purifying UDCA;
Treatment of every liver disease;
Treatment of primary biliary cirrhosis with another bile acid;
A diagnostic method for identifying primary biliary cirrhosis;
A fixed tablet strength independent of patient weight;
A treatment duration or biochemical endpoint.

This distinction matters because a formulation or manufacturing patent could have created a separate barrier even after the expiration of the method patent. U.S. Patent No. 4,859,660, based on the supplied claims, does not provide that type of protection.

When did U.S. Patent 4,859,660 expire?

The patent issued on August 22, 1989. Under the patent-term rules applicable to patents issued before June 8, 1995, the ordinary term was 17 years from issuance. The resulting ordinary expiration date was August 22, 2006. [1][2]

Event	Date
Patent issued	August 22, 1989
Ordinary patent term	17 years from issue
Ordinary expiration	August 22, 2006
Current status for ordinary enforcement	Expired

Patent term extension under 35 U.S.C. § 156 is generally associated with regulatory review of eligible products and does not appear to change the ordinary expiration analysis for this patent. The relevant commercial conclusion is that the patent is no longer an enforceable U.S. exclusivity right.

What was the regulatory significance of the patent?

The patent covered a method associated with the approved use of UDCA for primary biliary cholangitis. FDA-approved ursodiol products are used to reduce disease-related biochemical abnormalities and for management of primary biliary cholangitis. Current labeling generally identifies ursodiol tablets or capsules as prescription products for this indication. [3]

The patent did not establish the FDA approval itself. Patent rights and FDA approval operate through separate systems:

The patent created a private exclusionary right.
The FDA approved a drug product based on safety, efficacy, quality, and labeling requirements.
FDA approval does not extend an expired patent.
Patent expiration does not eliminate the need for an abbreviated new drug application or other applicable regulatory pathway.

Because the patent expired in 2006, it does not currently prevent FDA-approved generic manufacturers from seeking or maintaining approval for ursodiol products used for primary biliary cholangitis.

What is the Orange Book status of U.S. Patent 4,859,660?

The Orange Book lists patents and regulatory exclusivities associated with approved drug products. A patent may be listed for an approved product when it claims the drug substance, drug product, or an approved method of use under FDA listing rules. [4]

The practical status of U.S. Patent No. 4,859,660 is determined by two separate questions:

Whether it was listed against a specific ursodiol NDA; and
Whether any listing remains commercially operative after expiration.

An expired patent cannot block approval or launch through continuing patent exclusivity. If the patent was previously listed against an ursodiol product, its expiration would have removed the operative patent barrier. FDA Orange Book records should be read together with the patent’s legal status and the relevant NDA history rather than treated as a substitute for either.

For current commercial analysis, the patent should be categorized as an expired historical method-of-use patent, not as an active Orange Book barrier.

Were Paragraph IV challenges relevant to this patent?

Paragraph IV certifications are used when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. [5]

For U.S. Patent No. 4,859,660, Paragraph IV relevance was time-limited. An applicant could have challenged the patent while it was listed and unexpired. After August 22, 2006, the patent no longer presented a live patent term against a generic applicant.

The likely generic pathways were:

Paragraph IV certification if the patent was listed and unexpired at the time of filing;
A certification that the patent had expired;
A statement that no relevant patent was listed; or
Another certification permitted by the FDA’s ANDA rules.

The public commercial issue today is not whether a new applicant must defeat this patent. It is that the patent term has ended.

What generic entry risks exist for ursodiol?

The direct patent risk from U.S. Patent No. 4,859,660 is zero as an expired patent. Current generic entry risk is more likely to arise from regulatory, commercial, or unrelated intellectual-property factors.

Risk category	Relevance to ursodiol
Expired method patent	No continuing exclusionary effect
Active formulation patent	Must be checked separately for the specific product
Active manufacturing patent	Could affect a particular process, but not necessarily the finished product
FDA approval requirements	Remain applicable
Bioequivalence	Relevant to ANDA approval
Capsule or tablet supply	Commercial and manufacturing issue
Market concentration	Can affect shortage and pricing risk
New indication patents	Could affect a later indication if valid and listed
Biosimilar risk	Not applicable in the ordinary sense because UDCA is a small-molecule drug

Ursodiol is a chemically defined small molecule. It is not a biologic. Biosimilar approval under the Public Health Service Act is therefore not the relevant competitive pathway. Generic competition proceeds primarily under the Hatch-Waxman ANDA framework.

What formulation patents protect ursodiol products?

U.S. Patent No. 4,859,660 does not claim a formulation. Its fourth claim identifies gelatin capsules only as the dosage form used in the claimed treatment method.

A separate formulation patent would need to claim additional technical subject matter, such as:

A defined concentration of UDCA;
A particular excipient combination;
A dissolution profile;
A controlled-release system;
A liquid or suspension formulation;
A specific capsule shell;
A particle-size distribution;
A stability or manufacturing parameter.

No such formulation protection can be attributed to U.S. Patent No. 4,859,660 from the supplied claims. The patent landscape should therefore distinguish the expired therapeutic-use patent from any separate product patents associated with branded ursodiol products.

How strong was the patent estate for ursodeoxycholic acid?

The estate represented by U.S. Patent No. 4,859,660 was narrow in claim category but commercially relevant during its term.

Attribute	Assessment
Claim type	Therapeutic method
Active ingredient	Ursodeoxycholic acid
Disease	Primary biliary cirrhosis
Dose limitation	13 to 15 mg/kg/day in claim 2
Route limitation	Oral in claims 3 and 4
Dosage form limitation	Gelatin capsules in claim 4
Composition protection	None shown
Manufacturing protection	None shown
Current term	Expired
Current blocking value	None

During the patent term, claim 1 was the principal commercial claim because it covered treatment of the specified disease with an effective amount of UDCA without imposing the narrower dose, route, or capsule limitations. Claims 2 through 4 provided narrower fallback positions but could be avoided more easily by changing dose, route, or dosage form.

The estate did not have the characteristics of a broad platform patent. It did not control UDCA supply, all UDCA formulations, or all uses of UDCA. Its value depended on the relationship between the claimed indication and the clinical dosing practice used during the patent term.

Which companies challenged or competed with the patent?

A complete company-by-company litigation history cannot be inferred from the four claims alone. The supplied patent information identifies the legal scope but does not establish a definitive list of ANDA filers, Paragraph IV litigants, settlements, or licensees.

The competitive field included:

Branded ursodiol sponsors;
Generic manufacturers of ursodiol capsules and tablets;
Manufacturers supplying active pharmaceutical ingredient;
Companies with separate product or process rights;
Applicants seeking approval for the same primary biliary cholangitis indication.

There is no basis in the claims alone to conclude that a particular company obtained a license, entered a settlement, or prevailed in litigation involving this patent. Any such conclusion requires docket, Orange Book, FDA approval-history, and assignment-record evidence.

What licensing deals or settlements affected the patent?

The claims do not disclose licensing agreements or settlement terms. Patent assignment records also do not establish a commercial license unless the license is recorded or disclosed elsewhere.

The principal legal event evident from the patent chronology is expiration in 2006. After expiration:

A license was no longer required to practice the expired claims;
A settlement restricting generic entry would require separate contractual evidence;
An agreement concerning trademarks, supply, formulation technology, or another patent would not be evidence of a license to this patent itself.

What manufacturing and geographic barriers remain?

The patent was a U.S. patent and its direct exclusionary effect was territorial. It did not automatically create rights in Europe, Canada, Japan, or other jurisdictions.

Manufacturing barriers may still arise from:

Active foreign patents;
Active U.S. process patents;
Supplier contracts;
API quality requirements;
GMP compliance;
Stability and impurity controls;
FDA manufacturing-site obligations;
Scale-up and supply reliability.

Those barriers are distinct from the expired therapeutic-use claims. A manufacturer can avoid infringement of the patent while still facing regulatory or operational barriers to commercial supply.

How does this patent compare with a composition or formulation patent?

Issue	U.S. Patent 4,859,660	Composition patent	Formulation patent
Protects active ingredient itself	No	Often yes	Usually no
Protects use in PBC	Yes	Sometimes	Sometimes
Protects excipient system	No	No or limited	Yes
Protects manufacturing process	No	Sometimes	Sometimes
Avoidance by changing dose	Possible for narrower claims	Usually not	Sometimes
Avoidance by changing dosage form	Possible for claim 4	Usually not	Sometimes
Current status	Expired	Patent-specific	Patent-specific

A composition patent generally creates a broader product barrier than this method patent. A formulation patent may remain relevant even when a method patent has expired, but only if its claims are valid, enforceable, and applicable to the proposed product.

Key Takeaways

U.S. Patent No. 4,859,660 claims treatment of primary biliary cirrhosis with ursodeoxycholic acid.
Claim 1 is the broadest claim and requires an effective amount of UDCA administered to a patient with the disease.
Claim 2 narrows the dose to 13 to 15 mg/kg/day.
Claim 3 requires oral administration.
Claim 4 requires oral administration in gelatin capsules.
The patent does not claim UDCA itself, a composition, a formulation, or a manufacturing process.
The patent issued August 22, 1989, and its ordinary 17-year term ended August 22, 2006.
The patent is not a current barrier to generic ursodiol entry.
Biosimilar analysis is not applicable because UDCA is a small-molecule drug.
Any current risk must be assessed against separate formulation, process, regulatory, supply, or foreign patent rights.

FAQs

Can a generic company sell ursodiol for primary biliary cholangitis after the patent expired?

Yes. Expiration of the patent removed its U.S. exclusionary effect, subject to FDA approval and compliance with any unrelated valid patents.

Does a 1,000-mg daily ursodiol regimen infringe claim 2?

It depends on patient weight. The regimen falls within 13 to 15 mg/kg/day only for patients weighing approximately 66.7 to 76.9 kilograms.

Would a tablet infringe claim 4?

Not literally, because claim 4 requires gelatin capsules. A tablet could still implicate claim 1 if it is used to treat primary biliary cirrhosis with an effective amount of UDCA.

Does the patent cover treatment of primary biliary cholangitis?

The claim uses the historical term “primary biliary cirrhosis.” Whether that language covers the modern disease name depends on claim construction and the accepted medical meaning of the terminology. The modern FDA indication is generally described as primary biliary cholangitis.

Can a company manufacture UDCA without licensing this patent?

Yes, because the patent expired. Separate active patents, regulatory requirements, manufacturing controls, and contractual restrictions must still be evaluated.

References

U.S. Patent No. 4,859,660, “Treatment of primary biliary cirrhosis with ursodeoxycholic acid,” issued Aug. 22, 1989. United States Patent and Trademark Office.
35 U.S.C. § 154(c)(1). Patent term provisions for patents issued before June 8, 1995.
U.S. Food and Drug Administration. (n.d.). Ursodiol prescribing information. FDA-approved labeling.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Orange Book.
21 C.F.R. § 314.101 and § 314.107. Abbreviated new drug applications and patent certifications.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
France	86 16139	Nov 20, 1986

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	1318590	⤷ Start Trial
European Patent Office	0269516	⤷ Start Trial
France	2607005	⤷ Start Trial
Japan	S63141929	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,859,660

Summary for Patent: 4,859,660