US Patent 7,138,390: Obeticholic Acid Claim Scope, Expiration, and FXR Patent Landscape

US Patent 7,138,390 covered 6α-ethyl chenodeoxycholic acid, now known as obeticholic acid or OCA, together with selected salts, solvates, amino-acid conjugates, formulations, lipid-modifying uses, cardiovascular uses, and radiolabeled versions. The patent was the core composition-of-matter patent for OCA in the United States, but its enforceable term has ended. The patent therefore has historical importance and limited current blocking value unless a specific claim, reissue, or related patent remains independently enforceable.

What compound does US Patent 7,138,390 cover?

The patent claims a bile-acid derivative in which the variable R is ethyl. That compound is 6α-ethyl chenodeoxycholic acid, commonly called obeticholic acid.

Obeticholic acid is a synthetic farnesoid X receptor agonist. FXR regulates bile-acid homeostasis, hepatic lipid metabolism, cholesterol transport, and triglyceride handling. The compound was developed commercially as Ocaliva by Intercept Pharmaceuticals.

The patent’s claim architecture is unusual because it combines:

A core chemical compound claim.
Specific glycine and taurine conjugates.
Pharmaceutical formulation coverage.
FXR-mediated lipid and cardiovascular treatment methods.
Radiolabeled and tritiated versions for research use.

The supplied claim text does not reproduce the chemical drawing of formula I. The identity of the claimed ethyl compound follows from the patent family and the commercial development of OCA.

What are the independent claims in US 7,138,390?

Claims 1, 2, 3, 4, 5, 6, 8, and 10 are the principal claim categories. Claims 7, 9, and 11 depend on or narrow those categories.

Claim	Subject matter	Practical scope
1	Compound of formula I with R = ethyl, including pharmaceutically acceptable salts, solvates, or amino-acid conjugates	Core composition-of-matter claim
2	Glycine conjugate of the ethyl compound	Specific bile-acid conjugate
3	Taurine conjugate of the ethyl compound	Specific bile-acid conjugate
4	Pharmaceutical formulation containing the compound of claim 1	Product and formulation claim
5	Treatment of selected FXR-mediated lipid conditions	Method-of-use claim
6	Treatment of cardiovascular disease, including atherosclerosis and hypercholesterolemia	Method-of-use claim
7	Treatment of atherosclerosis under claim 6	Narrow method-of-use claim
8	Increasing HDL cholesterol	Physiological-effect claim
9	Lowering triglycerides	Physiological-effect claim, despite the apparent drafting error stating “increased”
10	Radiolabeled compound	Research and analytical use
11	Tritiated compound under claim 10	Narrow radiolabeled species

The commercial value was concentrated in claim 1. Claims 2 through 11 were narrower and generally more vulnerable to non-infringing product design, claim construction limits, or lack of commercial relevance.

How broad is claim 1 of US Patent 7,138,390?

Claim 1 is broad in legal category but narrow in chemical identity.

It does not claim all FXR agonists, all bile-acid derivatives, or all ethyl-substituted steroidal compounds. It claims one defined molecular scaffold with an ethyl substituent at the position specified in formula I. The claim then extends to:

Pharmaceutically acceptable salts.
Solvates.
Amino-acid conjugates.

The inclusion of salts and solvates prevents a generic manufacturer from avoiding the claim merely by using a different solid-state or ionization form of the same active moiety. The phrase “amino acid conjugates” is potentially broader than claims 2 and 3, but its enforceable reach depends on the structural disclosure and claim construction of formula I.

Composition-of-matter analysis

Claim 1 has the following elements:

The claimed formula I steroidal or bile-acid framework.
Ethyl substitution where the claim identifies R.
A permitted chemical form, including the parent compound, salt, solvate, or amino-acid conjugate.

A product containing obeticholic acid as the active ingredient would historically have presented a direct claim 1 risk. A product containing a materially different FXR agonist would not infringe merely because it treats the same disease or activates FXR.

The claim does not require:

A specific dose.
A particular route of administration.
A particular formulation excipient.
A particular purity level.
A specified crystalline form.
A specific patient population.
A requirement that the compound be used for liver disease.

Those omitted limitations made the claim commercially stronger than the method claims during the patent term.

What do claims 2 and 3 protect?

Claims 2 and 3 separately protect the glycine and taurine conjugates of the ethyl compound.

Bile acids naturally form conjugates with glycine and taurine. These conjugated species can have different pharmacokinetic, transport, solubility, and biological properties from the unconjugated acid.

Claim	Conjugate	Commercial relevance
2	Glycine conjugate	Narrow chemical claim; potentially relevant to metabolite or prodrug development
3	Taurine conjugate	Narrow chemical claim; potentially relevant to bile-acid transport and metabolism studies

A manufacturer using the unconjugated OCA parent would not avoid claim 1 by arguing that the compound is metabolized into a conjugate in vivo. Infringement generally focuses on the product made, used, or sold and the elements of the asserted claim. Conversely, a separately synthesized conjugate would face a more direct analysis under claims 2 or 3.

What formulation protection does claim 4 provide?

Claim 4 covers a pharmaceutical formulation comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

The claim is functional and generic. It does not specify:

Tablet or capsule form.
Immediate- or extended-release delivery.
A particular excipient.
A specific dissolution profile.
A particle-size distribution.
A crystalline form.
A particular dose strength.
A particular manufacturing process.

As a result, claim 4 would historically have reached many conventional OCA drug products. Its weakness is that a formulation claim with only a drug and a conventional carrier can face validity and construction issues if the specification does not support a meaningful technical distinction over known pharmaceutical compositions.

The claim is also subordinate to claim 1. If the compound in the formulation does not fall within claim 1, claim 4 cannot be infringed.

How does claim 4 compare with later formulation patents?

Later OCA patents were more likely to focus on specific solid forms, particle properties, dosing regimens, formulations, or treatment populations. Such patents can remain relevant after expiration of the original composition patent because they may have later expiration dates and narrower technical limitations.

A generic applicant could therefore face two separate questions:

Whether the active ingredient was covered by the expired composition patent.
Whether the proposed product or method practices an unexpired formulation, crystalline-form, dosing, or method patent.

What methods of treatment are covered?

Claims 5 through 9 protect selected uses of the compound. They are not composition claims and require proof of the claimed therapeutic method.

FXR-mediated lipid disorders

Claim 5 covers administering the compound to treat an FXR-mediated disease or condition selected from:

Hypercholesterolemia.
Hyperlipidemia.
Low HDL cholesterol.
High triglycerides.

The claim requires administration to a mammal suffering from the specified condition and use of a therapeutically effective amount.

Cardiovascular disease

Claim 6 covers treatment of cardiovascular disease where the disease is atherosclerosis or hypercholesterolemia. Claim 7 narrows claim 6 to atherosclerosis.

These claims are narrower than claim 1 because they require a particular therapeutic use. A product label that does not include the claimed indication reduces, but does not necessarily eliminate, method-of-use risk. Liability can still depend on prescribing patterns, promotional conduct, product instructions, and the facts surrounding induced infringement.

HDL and triglyceride claims

Claim 8 covers increasing HDL cholesterol. Claim 9 is intended to cover lowering triglycerides, although the supplied text states that the patient’s triglycerides are “to be increased.” That wording appears to be a drafting or transcription error. The title and surrounding claim structure indicate that the intended method was lowering triglycerides.

These claims require evidence that the administered compound produces the specified lipid effect. They do not claim every use of OCA or every FXR-mediated condition.

What do claims 10 and 11 cover?

Claim 10 covers a radiolabeled version of the compound. Claim 11 narrows that claim to a tritiated compound.

These claims have research value rather than ordinary therapeutic-product value. They could cover labeled OCA used in:

Receptor-binding assays.
Pharmacokinetic studies.
Tissue-distribution experiments.
Metabolism studies.
Analytical reference work.

They do not materially expand protection for commercial Ocaliva tablets. Their scope depends on the radiolabel being incorporated into the claimed compound while preserving the required formula.

When did US Patent 7,138,390 expire?

US Patent 7,138,390 issued on November 21, 2006. Public patent and Orange Book records identify March 19, 2023, as the patent’s listed expiration date. The date reflects the patent’s applicable term adjustment and patent-term calculations rather than the issue date alone (USPTO, 2006; FDA, 2024).

Milestone	Date
Patent family priority and filing activity	Early 2000s
US patent issued	November 21, 2006
Ocaliva FDA approval for primary biliary cholangitis	May 27, 2016
Listed US patent expiration	March 19, 2023

The patent is no longer an active US exclusion right after expiration. It cannot support a new injunction against an otherwise non-infringing product based solely on the expired claims.

What was the Orange Book status of US Patent 7,138,390?

US Patent 7,138,390 was listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, for Ocaliva tablets. The listing linked the patent to obeticholic acid products approved under Intercept’s new drug application (FDA, 2024).

An Orange Book listing is commercially important because it can trigger the patent-certification framework for an ANDA applicant. For a listed patent, an ANDA applicant generally must make one of the certifications permitted by the Hatch-Waxman statute, including:

Paragraph I: no patent information is listed.
Paragraph II: the patent has expired.
Paragraph III: the applicant will wait until patent expiration.
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

After March 19, 2023, a Paragraph II certification would generally be the relevant certification for this patent. A Paragraph IV challenge directed solely to the expired patent would have little practical purpose unless a dispute concerned pre-expiration conduct or a related patent right.

Which companies challenged Ocaliva patent protection?

The principal generic risk to Ocaliva was expected to arise from ANDA applicants challenging later-listed patents rather than from the expired US Patent 7,138,390.

Publicly reported OCA patent disputes have involved challenges directed at later patents covering formulations, crystalline forms, dosing, or methods of treatment. Those disputes must be separated from the '390 patent because an ANDA applicant can avoid an expired patent while still facing later Orange Book-listed rights.

The supplied claim set does not identify a specific Paragraph IV notice letter, ANDA applicant, or final judgment involving the '390 patent. The patent’s expiration means that current competitive analysis should focus on:

Later OCA composition or solid-form patents.
Formulation patents.
Dosing and method-of-use patents.
Patent-term extensions or pediatric extensions, if applicable.
Settlement agreements affecting generic launch dates.

What patent landscape surrounds obeticholic acid?

The OCA estate historically had several layers.

Patent layer	Technical subject	Business effect
Core composition patent	OCA and related forms	Primary historical barrier to generic entry
Conjugate patents	Glycine and taurine derivatives	Narrow chemical protection
Formulation patents	Tablets, carriers, solid forms, release properties	Product-specific protection
Crystalline-form patents	Polymorphs and solid-state forms	Can restrict manufacturing routes
Method patents	PBC, NASH, fibrosis, lipid, and dosing uses	Label and inducement risk
Manufacturing patents	Synthesis, purification, or crystallization	Process and supply-chain leverage
Regulatory exclusivity	Orphan-drug and approval exclusivity	Separate from patent rights

The commercial strength of the estate depended on whether later patents covered the actual proposed generic product. A generic could potentially design around a solid-form claim by using another form, but that may create stability, manufacturability, bioavailability, or regulatory problems.

Geographic coverage

US Patent 7,138,390 provided protection only in the United States. Parallel patent rights had to be assessed separately in Europe, Japan, Canada, Australia, and other markets. Expiration dates, supplementary protection certificates, patent-term adjustments, and national litigation outcomes vary by jurisdiction.

A US patent expiration did not eliminate OCA barriers in other countries. It also did not eliminate later US patents with different priority dates.

How does the patent estate compare with competing FXR agonists?

OCA was the first major FXR agonist to receive FDA approval. Its patent estate was therefore more mature than those of competing investigational FXR agonists.

FXR program	Sponsor or developer	Development position	Patent risk profile
Obeticholic acid	Intercept, later acquired by Alfasigma	FDA-approved for PBC during the relevant period	Core patent expired; later patents remained the principal issue
Cilofexor	Gilead Sciences	Clinical development	Separate composition and use estate
Tropifexor	Novartis	Clinical development	Separate nonsteroidal FXR agonist estate
EDP-305	Enanta Pharmaceuticals	Clinical development	Separate composition and method rights
Vonafexor	NorthSea Therapeutics and partners	Clinical development	Separate FXR agonist portfolio
Other nonsteroidal FXR agonists	Multiple companies	Early or mid-stage programs	Patent value depends on scaffold, selectivity, and indications

OCA is a steroidal bile-acid derivative. Several competing FXR programs use nonsteroidal scaffolds. Those compounds generally would not infringe claim 1 merely by sharing FXR activity or targeting the same disease.

What FDA regulatory exclusivity applied to Ocaliva?

Ocaliva received FDA accelerated approval for primary biliary cholangitis in 2016. The approved use was for adults with inadequate response to ursodeoxycholic acid or intolerance to ursodeoxycholic acid (FDA, 2016).

The product also received orphan-drug designation for PBC, which provided regulatory exclusivity separate from patent protection. Orphan exclusivity is indication-specific and time-limited. It does not extend the life of an expired composition patent and does not prevent approval of a different product for an unrelated indication unless the statutory orphan-exclusivity conditions apply.

OCA did not receive FDA approval for nonalcoholic steatohepatitis. Its failure in the REGENERATE confirmatory program materially reduced the value of the NASH method-of-use strategy and eliminated the prospect of a large additional approved market based on that indication (Intercept Pharmaceuticals, 2023).

What generic launch scenarios existed after patent expiration?

After the March 19, 2023 expiration of US Patent 7,138,390, the main launch scenarios were:

Immediate launch after regulatory readiness. A generic applicant could rely on a Paragraph II certification for the expired patent, subject to any remaining listed patents.
Launch after settlement. A later patent settlement could establish a date earlier than the last listed patent expiration.
At-risk launch. A company could launch while challenging later patents, accepting potential damages and injunction risk.
Design-around launch. A company could use a different crystalline form, formulation, process, or label if it avoided unexpired claims.
Delayed launch. Later method, formulation, or solid-form patents could postpone entry even though the core compound patent had expired.

The most important distinction is between active-ingredient freedom and product freedom. Expiration of the core OCA patent removes the principal molecule-level barrier. It does not automatically clear every product, process, or indication patent.

How strong was the US 7,138,390 patent estate?

During its term, the estate was strong at the composition level and weaker at the peripheral-claim level.

Claim category	Historical strength	Current position
Claim 1 compound	High, because it covered the active OCA molecule	Expired
Claims 2-3 conjugates	Moderate to high for directly made conjugates	Expired with the patent
Claim 4 formulation	Moderate; depends on carrier and claim construction	Expired
Claims 5-9 treatment methods	Variable; depends on indication, label, and evidence of use	Expired
Claims 10-11 radiolabeled compounds	Narrow research protection	Expired

The core claim’s value came from its ability to prevent substitution of a different solid form, salt, or conventional formulation from avoiding the active-ingredient claim. Once the patent expired, that advantage disappeared.

What licensing deals affected OCA commercialization?

OCA originated from academic bile-acid and FXR research associated with Roberto Pellicciari and collaborators. Commercial rights were developed through Intercept Pharmaceuticals, which held and commercialized OCA in the United States under the Ocaliva brand.

Intercept was acquired by Alfasigma in a transaction announced in 2023 and completed in early 2024. The acquisition transferred Ocaliva commercialization and the associated patent and regulatory portfolio to Alfasigma. The transaction did not revive expired patent rights and did not change the expiration date of US Patent 7,138,390.

Key Takeaways

US Patent 7,138,390 is the core historical OCA composition patent.
The claimed compound is obeticholic acid, or 6α-ethyl chenodeoxycholic acid.
Claim 1 covers the parent compound and specified salts, solvates, and amino-acid conjugates.
Claims 2 and 3 separately cover glycine and taurine conjugates.
Claim 4 covers pharmaceutical formulations with a carrier or diluent.
Claims 5 through 9 cover selected FXR, lipid, cardiovascular, HDL, and triglyceride uses.
Claims 10 and 11 cover radiolabeled and tritiated versions.
The listed US expiration date was March 19, 2023.
Current OCA generic risk depends primarily on later patents, not on the expired '390 patent.
A US patent analysis does not establish freedom to operate in Europe or other jurisdictions.
The failure of OCA’s NASH development program reduced the commercial value of later NASH-related method claims.
Alfasigma acquired Intercept and its OCA portfolio, but the acquisition did not extend the expired core patent.

FAQs

Can a generic manufacturer launch obeticholic acid after US Patent 7,138,390 expired?

Yes, the expired patent no longer blocks launch by itself. The applicant must still evaluate later Orange Book-listed patents, FDA requirements, manufacturing rights, and any applicable litigation or settlement restrictions.

Does a different salt of obeticholic acid avoid US Patent 7,138,390?

Historically, not necessarily. Claim 1 expressly included pharmaceutically acceptable salts. Because the patent has expired, the salt issue is now relevant mainly to historical infringement and to later patents directed to specific solid forms or formulations.

Does a nonsteroidal FXR agonist infringe the OCA patent?

Not merely because it activates FXR or treats the same condition. Infringement requires that the competing compound satisfy the structural limitations of the asserted claim.

Did US Patent 7,138,390 cover OCA treatment for NASH?

The claims supplied here do not expressly recite NASH. They cover selected lipid and cardiovascular conditions. Separate OCA patents and applications addressed other indications, including liver disease and NASH-related development programs.

Does FDA approval of Ocaliva extend the patent term?

FDA approval does not automatically extend the patent. Patent-term adjustment, patent-term extension, pediatric exclusivity, and orphan-drug exclusivity are separate mechanisms with distinct statutory requirements and durations.

References

Food and Drug Administration. (2016, May 27). FDA grants accelerated approval for obeticholic acid for primary biliary cholangitis. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
Intercept Pharmaceuticals, Inc. (2023). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.
United States Patent and Trademark Office. (2006). U.S. Patent No. 7,138,390, 6-alpha-ethyl chenodeoxycholic acid and its use in the treatment of FXR-mediated diseases. U.S. Department of Commerce.
Alfasigma S.p.A. (2024). Completion of acquisition of Intercept Pharmaceuticals. Corporate transaction announcement.

PCT Information
PCT Filed	February 21, 2002	PCT Application Number:	PCT/EP02/01832
PCT Publication Date:	September 19, 2002	PCT Publication Number:	WO02/072598

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1392714	⤷ Start Trial	300877	Netherlands	⤷ Start Trial
European Patent Office	1392714	⤷ Start Trial	CA 2017 00025	Denmark	⤷ Start Trial
European Patent Office	1392714	⤷ Start Trial	122017000034	Germany	⤷ Start Trial
European Patent Office	1392714	⤷ Start Trial	CR 2017 00025	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,138,390

Summary for Patent: 7,138,390