Details for Patent: 9,238,673

Which drugs does patent 9,238,673 protect, and when does it expire?

Patent 9,238,673 protects OCALIVA and is included in one NDA.

This patent has seventy-three patent family members in twenty-four countries.

Summary for Patent: 9,238,673

Title:	Preparation and uses of obeticholic acid
Abstract:	The present invention relates to obeticholic acid: or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.
Inventor(s):	André Steiner, Heidi Waenerlund Poulsen, Emilie Jolibois, Melissa Rewolinski, Ralf Gross, Emma Sharp, Fiona Dubas-Fisher, Alex Eberlin
Assignee:	Sigma Aldrich Co Ltd , Intercept Pharmaceuticals Inc
Application Number:	US13/919,734
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,238,673
Patent Claim Types: see list of patent claims	Composition;

US Patent 9,238,673: Obeticholic Acid Form 1 Claims, Exclusivity, and Generic Entry Risk

US Patent No. 9,238,673 protects pharmaceutical compositions containing obeticholic acid Form 1 with tightly controlled levels of specified impurities. Its commercial relevance is concentrated in crystalline-form and purity controls for obeticholic acid, the active ingredient in Ocaliva. The patent does not principally claim a method of treating primary biliary cholangitis, nonalcoholic steatohepatitis, a particular dose, or a manufacturing process.

The strongest claims require Form 1 obeticholic acid with:

• Less than 1% chenodeoxycholic acid;
• No more than 0.15% 6β-ethylchenodeoxycholic acid, with narrower dependent limits down to less than 0.05%;
• No more than 0.15% of a specified dimeric or ester-related impurity, with narrower limits down to less than 0.05%;
• In certain claims, less than 0.2% chenodeoxycholic acid;
• In claim 22, less than about 2% water; and
• A pharmaceutically acceptable carrier.

What does US Patent 9,238,673 protect?

The patent protects compositions rather than obeticholic acid as a molecule. The independent claims require both:

1. Obeticholic acid Form 1; and
2. A pharmaceutically acceptable carrier.

The purity limitations are part of the claimed subject matter. A composition falls within the claim only if the relevant impurity concentration and solid form limitations are met.

Claim group	Protected subject matter	Key limitation
Claims 1-8	Form 1 composition with chenodeoxycholic acid limits	Less than 1%, with dependent limits below 0.5%, 0.3% and 0.2%
Claims 1-5	Form 1 composition with 6β-ethylchenodeoxycholic acid limits	Not more than 0.15%, narrowing to less than 0.07%, 0.06% and 0.05%
Claims 9-12	Form 1 composition with a specified dimeric impurity	Not more than 0.15%, narrowing to less than 0.07%, 0.06% and 0.05%
Claims 13-18	Combination impurity controls	Both specified impurities at or below stated limits, with chenodeoxycholic acid limits
Claims 19-21	Highly purified Form 1 composition	Each of two specified impurities below about 0.05%, with chenodeoxycholic acid below 0.3% or 0.2%
Claim 22	Form 1 composition with moisture control	Less than about 2% water
Claim 23	Composition with all three named impurities controlled	6β-ethylchenodeoxycholic acid ≤0.05%, chenodeoxycholic acid ≤0.2%, and dimeric impurity ≤0.05%

The patent’s claim architecture is cumulative. The narrower claims incorporate the limitations of their parent claims. For example, claim 5 requires the claim 1 composition, the claim 2 impurity restriction, and the claim 3 and 4 narrowing sequence, resulting in a Form 1 composition with less than about 0.05% 6β-ethylchenodeoxycholic acid.

How do the claims distinguish Form 1 obeticholic acid?

Form 1 is a solid-state form of obeticholic acid. A generic or follow-on manufacturer would need to establish whether its active pharmaceutical ingredient is Form 1 using the analytical criteria disclosed in the patent specification, which may include powder X-ray diffraction, thermal analysis, spectroscopy, microscopy, or related solid-state methods.

The claims do not expressly define Form 1 in the claim text by a list of diffraction peaks. That creates two practical issues:

• The specification and prosecution history would likely control how Form 1 is construed.
• A product containing chemically identical obeticholic acid could avoid infringement if it uses a different polymorph or amorphous form, subject to the facts of the product and any other applicable patents.

The Form 1 limitation is therefore central. Testing only chemical purity would not resolve infringement. Solid-state characterization and impurity profiling would both be necessary.

What impurities are covered by US 9,238,673?

The patent identifies three relevant impurity categories.

Chenodeoxycholic acid

Chenodeoxycholic acid is a structurally related bile acid and a likely process- or synthesis-related impurity. The broadest claim 1 requires less than 1%. The dependent claims narrow the threshold to:

• Less than about 0.5%;
• Less than about 0.3%; and
• Less than about 0.2%.

Claim 23 uses the strictest chenodeoxycholic acid limit in the patent, requiring no more than about 0.2%.

6β-Ethylchenodeoxycholic acid

This compound is a close structural analog of obeticholic acid. The claims impose progressively stricter controls:

Claim level	Limit
Claims 2 and 13	Not more than 0.15%
Claim 3 and claim 14	Less than about 0.07%
Claim 4	Less than about 0.06%
Claims 5, 15 and 19	Less than about 0.05%
Claim 23	Between about 0% and not more than 0.05%

Specified dimeric or ester-related impurity

Claims 9-21 and 23 cover the compound identified in the claims as:

3α(3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oyloxy)-7α-hydroxy-6α-ethyl-5β-cholan-24-oic acid.

The limits mirror those applied to 6β-ethylchenodeoxycholic acid. The strictest claims require less than about 0.05%.

The long chemical name is commercially important because a generic applicant could not rely on routine assay data alone. The analytical method must distinguish this impurity from obeticholic acid and related bile-acid species with sufficient sensitivity at the 0.05% level.

How strong is the patent estate for obeticholic acid?

US 9,238,673 is strongest against a product that uses the same Form 1 material and meets the specified impurity profile. It is weaker against products using:

• A different polymorph;
• An amorphous form;
• A salt or derivative not covered by the claims;
• A materially different impurity profile;
• A product that does not contain the required pharmaceutical composition or carrier; or
• A process that produces a different solid form and does not convert to Form 1 before formulation.

The patent is not a broad composition-of-matter patent on obeticholic acid. Its value depends on whether the commercial product necessarily uses Form 1 with the claimed purity characteristics.

The dependent claims create fallback positions. If a court rejects or narrows the broad less-than-1% chenodeoxycholic acid limitation, claims 6-8 and 16-18 preserve narrower purity positions. Claims 19-23 provide the most commercially demanding combinations but also require more specific proof.

When does US 9,238,673 lose exclusivity?

US 9,238,673 issued on Jan. 19, 2016. The patent term is generally measured from the applicable earliest nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments. The patent’s exact expiration date should be taken from the USPTO Patent Center record and the Orange Book listing rather than calculated solely from the issue date.[1]

The patent does not receive a fresh 20-year term from issuance. The relevant term runs from the statutory patent-term start date. Any Hatch-Waxman patent-term extension would require a qualifying regulatory basis and FDA determination.

Event	Date or status
US patent issued	Jan. 19, 2016
Patent type	Composition claims directed to obeticholic acid Form 1 and impurities
FDA product association	Ocaliva, obeticholic acid
Regulatory exclusivity	Separate from patent term
Generic challenge mechanism	ANDA certification, including Paragraph IV if applicable
Expiration analysis	Must account for PTA, PTE and terminal-disclaimer data

What is the Orange Book status of Ocaliva?

Ocaliva is the FDA-approved product containing obeticholic acid. The Orange Book can list patents that claim the drug substance, drug product, formulation, or an approved method of use.[2]

US 9,238,673 is relevant to the drug-product and active-ingredient presentation because its claims require a pharmaceutical composition containing Form 1 obeticholic acid. It does not, based on the supplied claims, claim a disease-specific method of treatment or a particular tablet strength.

An Orange Book listing does not establish that every obeticholic acid product infringes. It gives an ANDA applicant a regulatory patent-certification pathway and allows the patent holder to invoke the 45-day litigation period after receiving a Paragraph IV notice.

The relevant regulatory distinction is:

• A patent claim determines potential infringement.
• An Orange Book listing determines the certification and approval framework for an ANDA.
• FDA approval does not resolve claim construction, validity, or infringement.

What Paragraph IV challenges affect obeticholic acid?

A generic applicant seeking approval before the expiration of an Orange Book-listed patent may submit a Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed. The patent holder may then file an infringement action within 45 days, triggering the statutory approval stay under the Hatch-Waxman framework.[3]

The risk analysis for US 9,238,673 would focus on four technical positions:

1. The proposed product does not contain Form 1.
2. The proposed product contains one or more impurities above the claimed thresholds.
3. The proposed product does not meet the pharmaceutical-composition limitation.
4. The claims are invalid for anticipation, obviousness, lack of written description, enablement, indefiniteness, or another statutory ground.

The most credible noninfringement route is likely a different solid form or a demonstrated impurity profile outside the claim limitations. A generic manufacturer that uses Form 1 and purifies the same three impurity classes to the claimed levels faces a more direct infringement risk.

No conclusion about a specific ANDA applicant, Paragraph IV notice, or litigation outcome should be drawn from the patent claims alone. Those facts must be established from FDA records, district-court dockets, and the Orange Book.

What formulation patents protect Ocaliva?

US 9,238,673 covers a composition containing Form 1 and a carrier, but the supplied claims do not require:

• A tablet;
• A particular excipient;
• A specific dose;
• A dissolution profile;
• A coating;
• A release mechanism;
• A particle-size distribution; or
• A specific manufacturing sequence.

This limits the patent’s formulation breadth. A tablet containing the claimed Form 1 material can fall within the claims even if the excipient system differs, because the claims require only a pharmaceutically acceptable carrier. Conversely, a formulation patent directed to a particular excipient combination or release profile could create separate infringement exposure even if a product avoids US 9,238,673.

Does the patent cover methods of use?

The supplied claims do not cover a method of treating primary biliary cholangitis, NASH, liver fibrosis, or another disease. They are composition claims.

This distinction matters in ANDA litigation. A generic applicant may face separate method-of-use patents listed for Ocaliva, even if it establishes noninfringement of US 9,238,673. A Section viii statement or carve-out may be relevant where a generic seeks approval only for non-patented indications or prescribing information can be legally limited.[3]

What manufacturing and intellectual-property barriers exist?

The principal manufacturing barriers are analytical and solid-state controls:

• Reproducible production of Form 1;
• Prevention or removal of closely related bile-acid impurities;
• Control of the dimeric impurity below 0.05% in the narrowest claims;
• Control of water below about 2% where claim 22 applies;
• Demonstration that drying, milling, storage, and tableting do not convert Form 1 into another form; and
• Validation of low-level impurity methods.

A manufacturer may avoid this patent by selecting a different polymorph, but that strategy can create separate regulatory and stability requirements. FDA chemistry, manufacturing, and controls review would still require characterization of the selected form, impurity profile, specifications, and stability behavior.[4]

How does US 9,238,673 compare with broader obeticholic acid patents?

Patent category	Typical protected subject matter	Relevance to US 9,238,673
Composition of matter	Obeticholic acid molecule or broad chemical class	Broader than the claims analyzed here
Polymorph	Form 1 or another crystalline form	Closely related and potentially overlapping
Purity composition	Form 1 with specified impurity limits	Core subject of US 9,238,673
Formulation	Tablet, excipient, coating or release profile	Potentially separate protection
Method of use	Treatment of PBC, NASH or liver disease	Not present in the supplied claims
Manufacturing process	Synthesis, purification, crystallization or drying	Separate process barrier
Regulatory exclusivity	FDA orphan, new chemical entity or clinical exclusivity	Independent of patent enforceability

What generic launch scenarios exist?

Scenario 1: Form 1 generic with the same impurity profile

This is the highest direct-infringement risk scenario. The applicant would likely need a Paragraph IV position against the relevant listed claims unless it launches after patent expiration or obtains a favorable judgment.

Scenario 2: Form 1 generic with impurity levels above the claimed thresholds

This may avoid some claims, but it creates a regulatory and quality-control issue. The impurity profile must remain within acceptable specifications and must not create safety or efficacy concerns.

Scenario 3: Non-Form 1 generic

A different polymorph or amorphous product has a stronger noninfringement position against the literal Form 1 limitation. Separate polymorph, formulation, process, or method-of-use patents could still apply.

Scenario 4: Authorized generic or license transaction

A license or authorized-generic arrangement could reduce litigation risk, but no licensing right can be inferred from US 9,238,673 itself. A commercial license would require a separate agreement and could include launch timing, territory, royalty, supply, or settlement provisions.

Key Takeaways

• US 9,238,673 is a purity-and-solid-form patent, not a broad obeticholic acid molecule patent.
• The claims require obeticholic acid Form 1 in a pharmaceutical composition.
• The narrowest claims control 6β-ethylchenodeoxycholic acid and the specified dimeric impurity below about 0.05%.
• Chenodeoxycholic acid is controlled below about 0.2% in the most restrictive claims.
• Claim 22 adds a water limit of less than about 2%.
• The patent does not claim a treatment method, dose, tablet design, or manufacturing process in the supplied claims.
• The key generic design-around is a non-Form 1 solid form or an impurity profile outside the claimed ranges.
• Orange Book listing and patent enforceability are separate issues.
• A Paragraph IV challenge would likely focus on Form 1 identification, impurity quantification, claim validity, and possible noninfringement.
• Exact expiration requires the USPTO and Orange Book term records, including patent-term adjustment, extension, and disclaimer data.

FAQs

Does US 9,238,673 cover all obeticholic acid products?

No. The claims require Form 1 obeticholic acid and specified impurity characteristics in a pharmaceutical composition.

Can a generic avoid the patent by using amorphous obeticholic acid?

Potentially, if the product does not contain Form 1 as claimed. Separate patents and FDA requirements may still apply.

Is claim 23 broader or narrower than claim 1?

Claim 23 is narrower in impurity content because it specifies limits for all three named impurities, including two at no more than 0.05% and chenodeoxycholic acid at no more than 0.2%.

Does the patent cover Ocaliva’s approved indication?

Not on the face of the supplied claims. The claims are directed to pharmaceutical compositions rather than treatment methods.

What testing is most important in an infringement analysis?

The critical testing includes solid-state identification of Form 1, quantitative measurement of the three named impurities, water content, and confirmation that the tested material is the active ingredient used in the finished composition.

References

1. United States Patent and Trademark Office. (2016). U.S. Patent No. 9,238,673, Obeticholic acid compositions.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (2017). Approved drug products and therapeutic equivalence evaluations; patent and exclusivity information.
4. U.S. Food and Drug Administration. (2016). Ocaliva (obeticholic acid) prescribing information.

Drugs Protected by US Patent 9,238,673

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Intercept	OCALIVA	obeticholic acid	TABLET;ORAL	207999-001	May 27, 2016		DISCN	Yes	No			Y
Intercept	OCALIVA	obeticholic acid	TABLET;ORAL	207999-002	May 27, 2016		DISCN	Yes	No			Y

International Family Members for US Patent 9,238,673

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013277429
Australia	2016200832
Australia	2016375566