United States Patent 8,058,267: Scope, Claims, Expiration, and Obeticholic Acid Patent Landscape

U.S. Patent No. 8,058,267 covers methods of treating cholestatic liver disease with 6α-ethyl-chenodeoxycholic acid, commonly known as obeticholic acid or OCA, and specified salts and amino-acid conjugates. The patent is method-of-use protection, not a broad composition-of-matter patent. Its expected 20-year term ended on or about October 24, 2024, subject to any patent-term adjustment. The claims do not cover every use of OCA, its manufacture, or its sale outside the claimed therapeutic context.

The patent was commercially important because OCA became the active ingredient in Ocaliva, marketed by Intercept Pharmaceuticals for primary biliary cholangitis, or PBC. Its principal economic value was the treatment method covering administration of OCA to mammals with cholestatic liver disease. The patent is now materially weaker as an exclusionary asset because its expected statutory term has ended and later OCA patents, rather than U.S. Patent 8,058,267, formed the principal basis of later Orange Book and generic-entry analysis.

What drug does U.S. Patent 8,058,267 protect?

The patent protects therapeutic use of the compound identified by formula I when R is ethyl. That compound is 6α-ethyl-chenodeoxycholic acid, or obeticholic acid.

Attribute	Analysis
Active compound	Obeticholic acid, also called 6α-ethyl-chenodeoxycholic acid
Drug product	Ocaliva
Drug class	Bile acid analogue; FXR agonist
Therapeutic area	Cholestatic liver disease
Primary FDA indication	Primary biliary cholangitis
Claim category	Method of treatment
Covered patient class	Mammals, with humans expressly recited in claim 5
Covered forms	Parent compound, pharmaceutically acceptable salts, glycine conjugate, and taurine conjugate
Patent number	U.S. 8,058,267
Issue date	November 15, 2011
Expected term end	Approximately October 24, 2024, subject to patent-term adjustment
Regulatory product linked to the invention	Ocaliva, NDA 207999

OCA is a semisynthetic bile acid derivative that activates the farnesoid X receptor, or FXR. FXR signaling affects bile-acid synthesis, transport, and metabolism. The asserted therapeutic concept was use of the ethyl-substituted bile acid for cholestatic liver disorders.

What do the claims of U.S. Patent 8,058,267 cover?

The claims establish a layered method-of-treatment scope.

Claim 1: Core treatment method

Claim 1 covers:

Treating cholestatic liver disease;
Administering a therapeutically effective amount;
To a mammal;
Of the formula I compound where R is ethyl;
Or a pharmaceutically acceptable salt or amino-acid conjugate of that compound.

The claim is broad within the disease and compound limitations. It is not restricted to a particular dosage, route of administration, formulation, disease stage, or named cholestatic disorder.

The claim does not cover:

Every use of OCA;
Nontherapeutic administration;
Manufacture of OCA;
A composition of OCA standing alone;
Treatment of a disease outside the claim's cholestatic-liver-disease limitation;
A product that does not contain OCA or a covered derivative;
Use of a different bile acid analogue.

The phrase "therapeutically effective amount" is a functional limitation. In litigation, infringement would normally turn on whether the accused product is administered in an amount intended to produce a therapeutic effect for a covered cholestatic liver disease.

Claim 2: Glycine conjugate

Claim 2 narrows claim 1 to the glycine conjugate of the formula I compound.

This claim does not cover OCA in every chemical form. It requires the glycine-conjugated species. A product containing only the unconjugated parent acid would fall outside claim 2, although it could remain relevant to claim 1.

Claim 3: Taurine conjugate

Claim 3 is directed to the taurine conjugate of the formula I compound.

As with claim 2, the limitation creates a species-specific claim. The taurine conjugate must be the administered therapeutic agent. This claim could be relevant to research involving endogenous bile-acid transport, metabolism, or conjugated bile-acid formulations, but it is less directly aligned with Ocaliva, whose marketed active ingredient is OCA rather than the taurine conjugate.

Claim 4: Pharmaceutically acceptable salt

Claim 4 narrows claim 1 to a pharmaceutically acceptable salt of the formula I compound.

The claim potentially reaches salt forms used to improve handling, stability, solubility, or formulation performance. The salt must remain pharmaceutically acceptable and must be administered for treatment of cholestatic liver disease.

A salt claim can have practical significance where a generic sponsor develops a different solid form or salt rather than copying the reference product's free-acid form. That protection is distinct from a crystalline-form patent, which would normally require structural or solid-state limitations.

Claim 5: Human treatment

Claim 5 narrows the mammal limitation to a human.

Claim 5 is important for commercial enforcement because Ocaliva is a human prescription drug. Claim 1 already includes humans through the broader mammal category, so claim 5 does not materially expand the scope. It provides a more specific human-treatment claim that may be useful for litigation or prosecution strategy.

How broad is the patent's legal scope?

The patent has meaningful breadth as a therapeutic-use patent but limited breadth as a pharmaceutical asset.

Scope category	Coverage under U.S. 8,058,267
OCA administered for PBC	Likely within claim 1 and potentially claim 5
OCA administered for another cholestatic liver disease	Potentially within claim 1 if the disease qualifies
OCA administered for NASH	Not necessarily within the claim because NASH is not inherently a cholestatic liver disease
OCA administered for a non-liver disease	Outside the express disease limitation
OCA composition	Not covered by these claims standing alone
OCA manufacturing process	Not covered
OCA tablet formulation	Not covered unless the formulation is used in the claimed method
Glycine conjugate for cholestatic disease	Covered by claim 2
Taurine conjugate for cholestatic disease	Covered by claim 3
Pharmaceutically acceptable OCA salt	Covered by claim 4 when used in the claimed treatment
Animal treatment	Covered by claim 1 if the remaining limitations are met
Human treatment	Specifically covered by claim 5

The largest interpretive issue is the meaning of "cholestatic liver disease." The term generally encompasses disorders involving impaired bile formation or bile flow. PBC is a classic cholestatic liver disease. Primary sclerosing cholangitis, biliary atresia, certain drug-induced cholestatic conditions, and other bile-flow disorders may also fall within the term depending on the evidence and claim construction.

The patent does not expressly name PBC in the supplied claims. That omission creates broader potential disease coverage than a claim limited to PBC, but it also creates litigation risk over whether a particular liver disorder is cholestatic within the ordinary meaning of the claim.

What formulation and chemical-form protection exists?

U.S. Patent 8,058,267 provides limited chemical-form protection through salts and amino-acid conjugates, but it is not a comprehensive formulation patent.

Parent compound

The principal product-relevant species is OCA itself, the ethyl-substituted bile acid. Claim 1 reaches administration of the parent compound.

Pharmaceutically acceptable salts

Claim 4 covers pharmaceutically acceptable salts. The claim does not identify a single salt by name in the text supplied. A salt must satisfy both requirements:

It must be a salt of the covered formula I compound; and
It must be pharmaceutically acceptable.

The claim does not automatically cover every excipient, co-crystal, polymorph, hydrate, solvate, or particle-size distribution.

Glycine and taurine conjugates

Claims 2 and 3 cover the glycine and taurine conjugates, respectively. These claims are narrower than claim 1 but may be relevant to alternative bile-acid delivery strategies or metabolic products.

Tablet and delivery-system protection

The supplied claims contain no explicit limitation to:

Immediate-release tablets;
Modified-release tablets;
Capsules;
Suspensions;
Injectable products;
Particular excipients;
Particle size;
Dissolution profiles;
Coatings;
Specific dose strengths.

Any separate formulation patent would need to be analyzed independently.

When does U.S. Patent 8,058,267 lose exclusivity?

The expected statutory term ended around October 24, 2024.

The relevant term calculation is generally based on the earliest effective U.S. nonprovisional or international filing date under the 20-year patent-term rule. Public patent-family records associate the patent with an October 24, 2003 priority date. The patent issued in 2011, but the late issue date did not independently extend the patent to 2031.

Event	Date or status
Earliest reported priority	October 24, 2003
Patent issued	November 15, 2011
Expected 20-year term endpoint	Approximately October 24, 2024
Patent-term adjustment	Must be confirmed from the issued patent and USPTO records
Patent-term extension	No established extension is identified for this patent
Current commercial significance	Limited as an enforceable patent after the expected term endpoint

The expiration of this patent does not automatically eliminate all OCA exclusivity. Later patents may cover OCA compositions, formulations, crystalline forms, manufacturing processes, or additional methods of use.

What was the Orange Book status of U.S. Patent 8,058,267?

U.S. Patent 8,058,267 should be distinguished from later patents associated with Ocaliva in the FDA Orange Book.

Orange Book listing depends on whether a patent claims the approved drug substance, drug product, or an approved method of use. A method patent must generally correspond to an approved use code. An expired patent may remain historically visible in regulatory and litigation records but no longer block generic approval after its enforceable term ends.

For Ocaliva, the more commercially relevant patent analysis has involved later OCA patents, including patents directed to drug substance, use, formulation, or solid-state characteristics. The supplied claims do not establish that U.S. 8,058,267 was the active Orange Book barrier at the time generic applicants filed abbreviated new drug applications.

The key regulatory distinction is:

Regulatory issue	Effect
Patent covering an approved method	May support a use code and a Paragraph IV certification
Expired method patent	Generally cannot support a continuing injunction after expiration
Unlisted method patent	May still be litigated, but does not necessarily create Orange Book approval delay
Composition patent	Can create broader generic-entry risk
Formulation or crystalline-form patent	May restrict a particular product design without covering all OCA products

What FDA exclusivity did Ocaliva receive?

Ocaliva received FDA accelerated approval on May 27, 2016, for treatment of PBC in adults with an inadequate response to ursodeoxycholic acid or who were unable to tolerate it. The approval was based on biochemical evidence, including reduction of alkaline phosphatase, rather than definitive evidence of improved transplant-free survival.

The FDA granted orphan-drug exclusivity for the PBC indication. Orphan exclusivity is separate from patent protection and generally lasts seven years from approval for the same indication.

FDA protection	Relevance
Accelerated approval	Approval based on a surrogate endpoint
Orphan-drug exclusivity	Seven-year period for the qualifying PBC indication
Pediatric exclusivity	Must be verified separately from FDA records
Patent exclusivity	Determined by the individual patent terms
NASH status	OCA did not obtain FDA approval for NASH

FDA later determined that OCA did not demonstrate the required clinical benefit for nonalcoholic steatohepatitis, or NASH. NASH-related development therefore did not create an approved method-of-use position equivalent to the PBC approval.

Which companies challenged Ocaliva patents?

The principal generic-entry risk has involved abbreviated new drug applicants and patent litigation directed at the broader Ocaliva patent estate, rather than only U.S. 8,058,267.

Relevant potential challengers have included established generic manufacturers and specialty generics companies that evaluate OCA products after patent expiry. A Paragraph IV certification can trigger litigation under the Hatch-Waxman Act if the NDA holder or patent owner sues within the statutory period.

For U.S. 8,058,267 specifically, the commercial effect of a Paragraph IV challenge is limited after the patent's expected 2024 expiration. A generic applicant would have little reason to litigate a patent that will expire before FDA approval or commercial launch unless the patent term, patent-term adjustment, or infringement position is disputed.

The important litigation questions are:

Which later OCA patents were listed for Ocaliva?
Whether a generic applicant made Paragraph IV certifications;
Whether Intercept or another patent owner filed a timely infringement action;
Whether the parties entered a settlement with a controlled launch date;
Whether any later patent remains enforceable after 2024.

What litigation and settlement issues affect generic entry?

A generic OCA applicant could face several distinct theories of infringement:

Direct infringement through labeling that instructs treatment of PBC;
Induced infringement through a label or promotional materials;
Infringement of a composition or formulation patent;
Infringement of a crystalline-form patent;
Process-patent issues involving manufacture or purification.

The 8,058,267 claims create a relatively straightforward method claim if the generic label instructs use for PBC. A carve-out strategy could theoretically omit a patented indication from the label, but that approach depends on whether the omitted use is commercially important and whether the remaining labeling still induces infringement.

A settlement could permit an authorized generic, a delayed launch, or a launch after the expiry of later patents. The expiration of 8,058,267 alone would not establish freedom to launch if later patents cover the drug product or its approved use.

How strong is the patent estate for Ocaliva?

The strength of U.S. 8,058,267 is moderate historically and weak as a current standalone exclusionary right.

Factor	Assessment
Claim breadth	Broad disease and mammal language, but limited to treatment
Chemical coverage	Focused on OCA and specified derivatives
Composition protection	Absent from the supplied claims
Formulation protection	Absent from the supplied claims
Disease coverage	Broad but potentially subject to claim-construction disputes
Human-use relevance	High because claim 5 expressly covers humans
Remaining term	Expected to have ended in October 2024
Design-around potential	Moderate for noncovered indications, formulations, or compounds
Litigation leverage after expiry	Low
Biosimilar relevance	None; OCA is a small molecule
Generic relevance	High historically and potentially significant after later patents expire

The patent was stronger as part of a portfolio than as an isolated patent. Its claim set could support an infringement case against a product labeled for cholestatic liver disease, but it did not independently block all OCA products.

How does this patent compare with later OCA patents?

Later OCA patents may offer more commercially durable protection if they cover the active ingredient, a particular solid form, a formulation, or a separate approved use.

Patent type	Commercial protection
U.S. 8,058,267 method patent	Administration of OCA or specified derivatives for cholestatic liver disease
Composition-of-matter patent	OCA molecule or defined chemical class
Formulation patent	Tablet, dosage form, excipient system, or release profile
Solid-state patent	Polymorph, crystalline form, hydrate, or solvate
Manufacturing patent	Synthesis, purification, or processing route
Later method patent	A distinct disease, patient population, dose, or treatment schedule

A generic sponsor can avoid a formulation patent by developing a different formulation, but it cannot avoid a valid composition patent while selling the same active ingredient. That hierarchy makes composition and solid-state patents more important to launch timing than an expired method patent.

What manufacturing and geographic barriers remain?

U.S. 8,058,267 does not create a manufacturing monopoly. It does not claim a synthetic route, starting material, purification sequence, or production facility.

Manufacturing risk may arise from separate patents covering:

Stereoselective synthesis of the 6α-ethyl substituent;
Resolution of intermediates;
Purification of OCA;
Crystalline or amorphous forms;
Control of impurities;
Scale-up processes.

Geographically, the patent's enforceability is limited to the United States. Corresponding patents in Europe, Canada, Japan, China, or other jurisdictions require separate analysis. U.S. expiration does not terminate foreign rights, although corresponding foreign patents may have similar priority-based expiry dates.

What is the commercial exposure?

Ocaliva was Intercept's principal commercial product and generated several hundred million dollars in annual net sales before the company was acquired by Alfasigma. Patent expiry therefore affected a material revenue stream.

The revenue exposure depends on:

Whether OCA generics receive FDA approval;
The number of approved ANDAs;
Whether later OCA patents remain enforceable;
Whether FDA labeling permits an indication carve-out;
Whether the branded product remains available;
Reimbursement and prescribing trends following patent expiry.

The absence of biosimilar risk is significant. OCA is a chemically synthesized small molecule, so the relevant competitive pathway is an ANDA-based generic, not a biologics license application or biosimilar pathway.

Key Takeaways

U.S. Patent 8,058,267 is a method-of-treatment patent for OCA, not a broad composition patent.
Claim 1 covers administration of OCA, its pharmaceutically acceptable salts, and amino-acid conjugates for cholestatic liver disease.
Claims 2 and 3 specifically cover the glycine and taurine conjugates.
Claim 4 covers pharmaceutically acceptable salts.
Claim 5 expressly limits the mammal to a human.
The claims do not expressly cover manufacture, formulation design, crystalline form, or every use of OCA.
The expected patent term ended around October 24, 2024, subject to any patent-term adjustment.
Ocaliva received FDA accelerated approval for PBC, not NASH.
Generic competition is governed by the full Ocaliva patent estate, not this patent alone.
Biosimilar rules do not apply because OCA is a small molecule.
Later composition, formulation, solid-state, manufacturing, or method patents may remain more important to launch timing than U.S. 8,058,267.

FAQs

Does U.S. Patent 8,058,267 cover Ocaliva tablets?

It can cover the use of Ocaliva tablets when administered to treat cholestatic liver disease, but the claims do not independently claim the tablet formulation or its excipients.

Does the patent cover OCA treatment for NASH?

The supplied claims require treatment of cholestatic liver disease. NASH is not automatically within that category, and the patent should not be treated as a general NASH-use patent.

Can a generic company launch OCA after this patent expires?

Not necessarily. A generic company must assess all unexpired OCA patents, FDA Orange Book listings, regulatory exclusivities, manufacturing patents, and potential induced-infringement theories.

Are glycine and taurine conjugates the same as obeticholic acid?

No. They are chemically distinct conjugated derivatives. Claims 2 and 3 separately identify those species, while Ocaliva uses OCA as its active ingredient.

Is U.S. Patent 8,058,267 relevant to biosimilar litigation?

No. OCA is a small-molecule drug. Competitive products proceed through the generic drug framework, principally under the ANDA pathway, rather than the biosimilar pathway.

References

U.S. Patent and Trademark Office. (2011). United States Patent No. 8,058,267: Methods of treating cholestatic liver diseases.
U.S. Food and Drug Administration. (2016). FDA approves Ocaliva for rare, chronic liver disease.
U.S. Food and Drug Administration. (2024). Drugs@FDA: Ocaliva (obeticholic acid), NDA 207999.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
Intercept Pharmaceuticals, Inc. (2023). Annual report on Form 10-K. U.S. Securities and Exchange Commission.
U.S. Food and Drug Administration. (2023). FDA issues complete response letter for Ocaliva for treatment of NASH.

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
European Patent Office	1392714	⤷ Start Trial	23/2017	Austria	⤷ Start Trial
European Patent Office	1392714	⤷ Start Trial	1790020-0	Sweden	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,058,267

Summary for Patent: 8,058,267