US Patent 8,377,916: Scope, Claims, Expiration, Orange Book Status, and Obeticholic Acid Patent Landscape

US Patent No. 8,377,916 covers dose- and route-specific methods of treating cholestatic liver disease and lipid disorders with 6-alpha-ethylchenodeoxycholic acid, commonly known as obeticholic acid or OCA. The patent is a method-of-treatment patent, not a composition-of-matter patent. Its core protection is limited to administering a pharmaceutical composition containing the claimed compound at a dose of 0.01 mg/kg to 100 mg/kg per dose.

The patent was assigned to Intercept Pharmaceuticals, Inc. and is associated with Ocaliva, the FDA-approved obeticholic acid product. Its ordinary patent term is expected to end in 2026, subject to any applicable patent-term adjustment, patent-term extension, pediatric extension, terminal disclaimer, and Orange Book listing status.

What drug and active ingredient does US Patent 8,377,916 protect?

The compound identified by formula I with R equal to ethyl is obeticholic acid, also called 6-alpha-ethyl chenodeoxycholic acid.

Obeticholic acid is a semisynthetic bile acid and farnesoid X receptor agonist. Ocaliva was approved by the FDA in 2016 under the accelerated approval pathway for adults with primary biliary cholangitis who had an inadequate response to or intolerance of ursodeoxycholic acid. The FDA later limited or changed the product's regulatory position following safety and confirmatory-trial developments. The patent's legal scope remains separate from the drug's current regulatory status.

The claim language also covers:

Pharmaceutically acceptable salts of the claimed compound.
Amino acid conjugates of the claimed compound.
Pharmaceutical compositions containing the compound.
At least one carrier or diluent.
Administration for specified diseases.
Doses from 0.01 mg/kg to 100 mg/kg per dose.
Oral administration under dependent claim 2.
Single daily dosing under dependent claim 3.

The patent does not claim every use of every bile acid or every FXR agonist. It is directed to the specified compound, the listed disease indications, and the stated administration parameters.

What are the independent and dependent claim limitations?

Claim 1: Core method-of-treatment claim

Claim 1 requires all of the following elements:

Limitation	Scope
Treatment method	Administration to treat a listed disease
Diseases	Cholestatic liver disease, atherosclerosis, arteriosclerosis, hypercholesteremia, or hyperlipidemia
Active ingredient	Compound of formula I with R equal to ethyl
Alternative forms	Pharmaceutically acceptable salt or amino acid conjugate
Formulation	Pharmaceutical composition
Excipients	At least one pharmaceutical carrier or diluent
Dose	0.01 mg/kg to 100 mg/kg per dose

A product or clinical regimen must satisfy every required limitation to fall within the literal scope of claim 1. A formulation containing OCA alone is not enough. The use must also be directed to one of the listed disease categories and must use a dose within the claimed range.

The dose range is broad. It covers low-dose and high-dose regimens, including the 5 mg and 10 mg daily doses historically associated with Ocaliva. A dose expressed in fixed milligrams must be converted to mg/kg to determine whether it falls within the claim.

Claim 2: Oral administration

Claim 2 narrows claim 1 by requiring oral administration. It is relevant to oral tablets, capsules, solutions, and other oral dosage forms containing OCA.

An oral generic product used for a listed disease and within the claimed dosage range would present a direct infringement risk if the generic label encourages or permits the claimed method. The existence of a dependent claim does not limit claim 1 to oral use. Claim 1 is broader because it does not specify a route.

Claim 3: Single daily dose

Claim 3 narrows claim 1 by requiring administration as a single daily dose. The claim is commercially important because Ocaliva labeling has used once-daily administration.

A twice-daily regimen may avoid claim 3 but would not necessarily avoid claim 1. Claim 1 is drafted in terms of dose per administration and does not require once-daily dosing.

Claim 4 and additional dependent claims

The supplied claim excerpt ends before the full text of claim 4. The patent's dependent claims further narrow the treatment method by specifying dosage, dosing frequency, patient population, or administration conditions. The enforceability analysis must use the issued claim text rather than an incomplete excerpt.

The core commercial point is that claims 2 through the later dependent claims create narrower fallback positions around oral dosing, once-daily administration, and particular dose ranges. They do not expand the disease, compound, or route limitations in claim 1.

What diseases are covered by US 8,377,916?

The patent identifies five broad disease categories:

Cholestatic liver disease.
Atherosclerosis.
Arteriosclerosis.
Hypercholesteremia.
Hyperlipidemia.

The broadest practical value lies in cholestatic liver disease, particularly primary biliary cholangitis. The cardiovascular and lipid-disorder categories expand the literal claim scope but may have less commercial relevance because Ocaliva's principal approved market has been hepatology rather than lipid management.

“Cholestatic liver disease” may cover several conditions involving impaired bile flow, depending on the patent specification, claim construction, and the facts of the accused use. Primary biliary cholangitis is the most commercially relevant application because it was the basis for Ocaliva's FDA approval.

The specification's disclosure cannot automatically enlarge the claims. A treatment outside the listed conditions may fall outside claim 1 even if the specification discusses additional diseases.

What dosage forms and formulations are protected?

The patent protects use of a pharmaceutical composition containing the claimed compound and at least one carrier or diluent. It does not appear, from the quoted claims, to require a particular tablet composition, crystalline form, particle size, release profile, or excipient combination.

Formulation scope

The formulation limitation is broad enough to cover conventional pharmaceutical presentations, including:

Immediate-release oral tablets.
Capsules.
Oral solutions or suspensions.
Compositions containing salts or amino acid conjugates.
Products with conventional carriers or diluents.

The claim does not require a specific excipient. A carrier or diluent can include ordinary pharmaceutical ingredients used to manufacture a dosage form.

What the patent does not necessarily cover

The quoted claims do not independently claim:

A specific crystalline polymorph.
A particular tablet hardness or dissolution profile.
A controlled-release formulation.
A specific OCA particle-size distribution.
A manufacturing process.
A formulation containing a defined excipient percentage.
OCA as a chemical compound without the claimed therapeutic use.

Separate patents may address those subjects. A generic manufacturer could therefore face different infringement questions under composition, formulation, polymorph, process, and method-of-use patents.

When does US Patent 8,377,916 lose exclusivity?

The patent was granted on February 19, 2013. Public patent records identify a priority date in 2006 and an expected ordinary expiration in 2026. The practical exclusivity date must be determined from the USPTO patent record, including any patent-term adjustment or disclaimer.

Event	Date or period
Earliest priority period	2006
Patent application publication	Before grant
Grant of US 8,377,916	February 19, 2013
Expected ordinary patent expiration	2026
Drug product associated with patent	Ocaliva, obeticholic acid
Relevant regulatory pathway	FDA accelerated approval
Patent type	Method of treatment

Patent expiration does not itself authorize commercial launch if another unexpired patent, pediatric extension, regulatory exclusivity period, or court order remains applicable. Conversely, an Orange Book-listed patent may be challenged before expiration through an ANDA Paragraph IV certification.

What is the Orange Book status of US 8,377,916?

Ocaliva's Orange Book patent estate has included method-of-use and related patents covering obeticholic acid products. The precise listing status can change as FDA records are updated, patents expire, or the reference-listed drug sponsor submits certifications.

The Orange Book is relevant because an ANDA applicant must address listed patents through one of four certifications:

Paragraph I: No patent information has been submitted.
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.

For a method-of-use patent, an ANDA applicant may seek a section viii carve-out if the FDA-approved labeling contains a use protected by the patent and the applicant can omit that use from its proposed label. A carve-out is not always available where the remaining label, prescribing information, or promotional conduct still encourages the patented method.

Which companies are challenging Ocaliva patent protection?

Publicly reported generic activity has focused on Ocaliva's commercial opportunity and the expiration of Intercept's patent estate. The relevant challenger analysis depends on the individual ANDA, the patents certified, the dates of notice letters, and whether the reference-listed drug sponsor filed a patent-infringement action within the statutory 45-day period.

A Paragraph IV challenge would create a Hatch-Waxman litigation risk for:

The ANDA applicant.
Intercept Pharmaceuticals or its successor rights holder.
Any licensee or commercialization partner with enforcement rights.
The generic applicant's commercial launch plans.

The existence of a Paragraph IV notice does not establish that the patent is invalid or that the generic will launch. It starts a statutory framework that can trigger a 30-month FDA approval stay if the patent owner timely files suit. The stay may be shortened, terminated, or avoided under circumstances specified in the Hatch-Waxman statute.

No reliable conclusion about a particular company's challenge should be drawn solely from the existence of an Ocaliva generic listing. The relevant evidence is the FDA ANDA record, patent-holder litigation complaint, notice-letter disclosures, and subsequent docket activity.

What patent litigation affects US 8,377,916?

The principal litigation issues for this patent would be:

Whether the accused product is the claimed compound or a covered salt or conjugate.
Whether the proposed indication falls within the listed disease categories.
Whether the dose is within 0.01 mg/kg to 100 mg/kg per dose.
Whether the generic label induces administration for the patented use.
Whether a section viii label carve-out is legally effective.
Whether the claims are anticipated or obvious over prior bile-acid and FXR literature.
Whether the patent's written description and enablement support the full disease and dose scope.
Whether any terminal disclaimer or patent-term adjustment changes the expiration date.

A method-of-use patent can be harder to enforce against a generic than a compound patent because infringement often depends on the product label and prescribing behavior. A label that omits the patented indication may reduce direct inducement exposure. A label that includes the indication, dose, or once-daily regimen can create a stronger infringement case.

How strong is the patent estate for obeticholic acid?

The OCA estate is stronger when multiple patent categories overlap:

Patent category	Protection objective	Generic risk
Compound patents	OCA molecule or chemical class	Highest barrier if unexpired
Method-of-use patents	PBC, cholestatic disease, NASH, or lipid disorders	Depends on label and indication
Formulation patents	Tablets, excipients, release profile	Product-specific
Polymorph patents	Crystalline or solid-state forms	Depends on generic manufacturing route
Process patents	Synthesis or purification	Depends on process evidence
Regulatory exclusivity	FDA market protection	Separate from patent validity

US 8,377,916 is valuable as a method-of-use patent but is narrower than a valid, unexpired compound patent. Its enforceability depends heavily on the approved indication, generic labeling, dosing instructions, and the ability to prove induced infringement.

The patent also has a vulnerability associated with its breadth. Claim 1 covers multiple diseases and a 10,000-fold dose range from 0.01 mg/kg to 100 mg/kg. A challenger could attack written description, enablement, anticipation, or obviousness based on prior disclosures of bile acids, FXR agonism, cholesterol regulation, and cholestatic disease treatment. The patent's practical strength therefore depends on the specification's experimental support and the quality of the prior-art record.

What generic launch scenarios exist for Ocaliva?

Launch after patent expiration

This is the lowest-risk pathway if all relevant patents and regulatory protections have expired. A generic applicant can launch subject to FDA approval and ordinary substitution rules.

Paragraph IV launch

A generic applicant may certify that the patent is invalid, unenforceable, or not infringed. The applicant may launch after litigation milestones, a court decision, settlement terms, or risk-adjusted business approval.

Section viii carve-out

The applicant may remove the patented use from its label. This approach is more defensible where the remaining indications and dosing instructions do not encourage the patented method.

At-risk launch

A generic company may launch before final resolution if it determines that expected litigation damages and injunction risk are acceptable. This strategy is particularly sensitive to the commercial value of the product and the likelihood of injunctive relief.

How does US 8,377,916 compare with other OCA patents?

US 8,377,916 should be separated from patents covering the molecule itself, solid forms, formulations, and later clinical uses.

Issue	US 8,377,916	Compound or formulation patent
Patent type	Method of treatment	Chemical composition or product
Main limitation	Disease, dose, and administration	Molecule, form, or formulation
Infringement evidence	Label, use, dose, prescribing	Product testing and manufacturing evidence
Carve-out potential	Relatively significant	Usually limited
Commercial leverage	Strongest for protected indications	Stronger across all uses
Expiration sensitivity	2026 expected term	Must be assessed patent by patent

A generic company may avoid one method-of-use patent while remaining exposed to a formulation or polymorph patent. Conversely, a successful section viii carve-out may reduce exposure to US 8,377,916 without resolving other patents in the OCA estate.

What licensing and ownership issues affect the patent?

Intercept Pharmaceuticals developed and commercialized OCA and later entered into strategic transactions involving its product portfolio. Ownership, enforcement rights, and licensing rights should be verified against current USPTO assignment records and transaction documents.

For diligence purposes, the relevant questions are:

Who owns US 8,377,916 today?
Is the patent assigned, licensed, or subject to security interests?
Does the rights holder control Orange Book submissions?
Does a licensee have the right to sue generic applicants?
Are settlement or supply agreements confidential?
Are there territorial restrictions outside the United States?

A corporate acquisition or product sale does not automatically resolve the patent's validity, expiration, or enforceability. It changes the identity of the party controlling prosecution, listing, licensing, and litigation decisions.

What geographic coverage does the patent provide?

US 8,377,916 provides protection only in the United States. It does not directly protect OCA use in Europe, Japan, Canada, China, or other markets.

International protection must be assessed separately by patent family and national phase. Differences can arise in:

Claim wording.
Priority dates.
Patent-term calculations.
Patentability standards.
Supplementary protection certificates.
Regulatory exclusivity.
National litigation outcomes.
Orange Book-equivalent listing systems.

A US generic launch does not determine launch rights in other countries.

Key Takeaways

US 8,377,916 is a method-of-treatment patent for obeticholic acid, its salts, and amino acid conjugates.
Claim 1 covers specified cholestatic, cardiovascular, and lipid disorders at 0.01 mg/kg to 100 mg/kg per dose.
Dependent claims narrow the scope to oral administration, single daily dosing, and additional dosing conditions.
The patent does not independently claim OCA as a chemical compound or require a specific tablet formulation.
Its expected patent term ends in 2026, subject to the USPTO term calculation and any applicable extension.
Generic risk turns on the proposed label, dose, indication, section viii carve-out, and the status of other OCA patents.
The patent is commercially important but inherently narrower than a valid, unexpired compound-of-matter patent.
The OCA estate must be analyzed as a portfolio covering methods, formulations, solid forms, processes, regulatory exclusivity, and litigation.

FAQs About US Patent 8,377,916

Does US 8,377,916 cover all obeticholic acid products?

No. It covers specified methods using OCA or covered derivatives for listed diseases within the claimed dose range. It does not automatically cover every OCA product or every use.

Can a generic launch with a section viii carve-out avoid this patent?

Potentially. The carve-out must remove the patented use and avoid label language that encourages the protected method. It does not eliminate exposure under other OCA patents.

Is primary biliary cholangitis covered by the patent?

Primary biliary cholangitis is a cholestatic liver disease and is the principal commercial disease category connected with Ocaliva. The exact infringement analysis depends on the issued claim, label, dose, and use.

Does patent expiration eliminate FDA regulatory exclusivity?

No. Patent rights and FDA regulatory exclusivity are separate. Each must be checked independently.

Can a formulation patent extend protection after US 8,377,916 expires?

Yes. A valid, unexpired formulation, polymorph, process, or later method-of-use patent may continue to restrict a generic product after the expiration of this method patent.

References

U.S. Patent and Trademark Office. (2013). U.S. Patent No. 8,377,916, methods of treating cholestatic liver diseases.
U.S. Food and Drug Administration. (2016). Ocaliva prescribing information: Obeticholic acid.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2023). Orange Book: Approved drug products with therapeutic equivalence evaluations.
U.S. Code, 21 U.S.C. § 355. (2024). New drugs and abbreviated applications.
U.S. Code, 35 U.S.C. §§ 154, 156. (2024). Patent term and patent term extension.

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
European Patent Office	1392714	⤷ Start Trial	LUC00018	Luxembourg	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,377,916

Summary for Patent: 8,377,916