Details for Patent: 8,691,860

Which drugs does patent 8,691,860 protect, and when does it expire?

Patent 8,691,860 protects VIBERZI and is included in one NDA.

This patent has thirty-nine patent family members in twenty-four countries.

Summary for Patent: 8,691,860

Title:	Crystals and process of making 5-({(2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(-4-phenyl-1h-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid
Abstract:	The present invention relates to a novel crystals of 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1h-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid and methods of making the zwitterion of 5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1h-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.
Inventor(s):	Luigi Anzalone, Frank J. Villani, Christopher A. Teleha, Penina Feibush, Barry Fegely
Assignee:	Allergan Holdings ULC
Application Number:	US13/987,009
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,691,860
Patent Claim Types: see list of patent claims	Use;

United States Drug Patent 8,691,860: Eluxadoline Alpha-Crystal Claims, Patent Scope, and Market Exclusivity

U.S. Patent No. 8,691,860 protects the alpha crystalline form of eluxadoline, the active pharmaceutical ingredient in Viberzi. Its core protection is a solid-state product claim, supported by powder X-ray diffraction, thermal gravimetric analysis, and differential scanning calorimetry limitations. Claim 9 extends protection to treatment of irritable bowel syndrome, pain, and other opioid-receptor disorders when the alpha crystal is administered.

The patent is materially different from a conventional composition-of-matter patent. It does not broadly claim every form of eluxadoline. It targets a specified polymorph and selected pharmaceutical uses. A generic manufacturer can potentially avoid literal infringement by developing a different polymorph, amorphous material, salt, solvate, or formulation, although regulatory and equivalence issues may still create commercial barriers.

What drug does U.S. Patent 8,691,860 protect?

The protected compound is eluxadoline, chemically identified in the patent as:

5-({[2-amino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionyl]-[1-(4-phenyl-1H-imidazol-2-yl)-ethyl]-amino}-methyl)-2-methoxy-benzoic acid.

Eluxadoline is a locally acting mixed opioid-receptor ligand. It has mu-opioid receptor agonist and delta-opioid receptor antagonist activity, with additional activity at the kappa receptor. The FDA approved eluxadoline tablets under NDA 206940 as Viberzi for adults with irritable bowel syndrome with diarrhea, or IBS-D.[1]

Patent and product identification

Item	Information
Patent	U.S. Patent No. 8,691,860
Patent type	Polymorph and method-of-treatment patent
Protected material	Alpha crystalline form of eluxadoline
Brand	Viberzi
Active ingredient	Eluxadoline
FDA application	NDA 206940
Approval date	May 27, 2015
Original developer	Furiex Pharmaceuticals
Later commercial ownership	Forest/Actavis/Allergan, subsequently AbbVie
Primary indication	IBS-D
Earliest relevant priority	2009 priority filing identified in the patent family
Expected ordinary patent-term endpoint	Approximately June 2029, subject to patent-term adjustment and Orange Book records

The patent’s importance comes from the solid-state form used in the pharmaceutical product, not from a broad claim to the eluxadoline molecule in every physical state.

What are the independent claims of U.S. Patent 8,691,860?

The patent contains two commercially important claim concepts.

Claim 1: Alpha crystalline eluxadoline

Claim 1 covers:

The Form alpha crystal of eluxadoline.

This is a product-by-form claim. The chemical identity alone is not enough. The accused material must also possess the alpha crystalline form.

The claim does not expressly require a particular dosage form, excipient, tablet strength, or manufacturing process. It can therefore reach the alpha crystal as an active pharmaceutical ingredient before it is incorporated into a tablet or capsule.

Claim 9: Treatment using the alpha crystal

Claim 9 covers a method of treating a mammal suffering from:

• Irritable bowel syndrome;
• Pain; or
• Another opioid receptor disorder,

by administering an effective amount of the alpha crystal.

The claim is narrower than a generic method-of-use claim because the administered material must be the Form alpha crystal. It also requires a qualifying therapeutic use and an effective amount.

The IBS language is broader than the FDA-approved label in one respect because it recites irritable bowel syndrome generally, while Viberzi is approved specifically for IBS-D. FDA labeling and induced-infringement analysis would remain important in assessing a generic product directed to IBS-D.[1]

How do claims 2 through 8 define the alpha crystal?

Claims 2 through 8 are dependent characterization claims. They provide analytical markers for identifying the polymorph.

Claim	Characterization limitation
2	PXRD peaks at approximately 14.0, 14.3, and 14.7 degrees 2-theta
3	PXRD peaks at approximately 10.2, 11.3, 14.0, 14.3, and 14.7 degrees 2-theta
4	PXRD peaks at approximately 10.2, 11.3, 11.8, 14.0, 14.3, 14.7, 16.1, and 18.3 degrees 2-theta
5	PXRD peaks substantially as shown in Table 1
6	PXRD peaks substantially similar to Figure 1
7	TGA substantially similar to Figure 2
8	DSC substantially similar to Figure 3

These claims create multiple evidentiary routes for proving that a material is the alpha form. A product may satisfy claim 1 even if it does not fall within every dependent claim. Conversely, failure to reproduce one listed peak does not necessarily defeat claim 1 if the material otherwise is the claimed alpha polymorph.

What does “about” mean in the PXRD claims?

The terms “about” and “substantially similar” create tolerance around the reported analytical values. Powder X-ray diffraction results can shift because of:

• Instrument calibration;
• Sample preparation;
• Particle size;
• Preferred orientation;
• Hydration or solvent content;
• Radiation source;
• Data-processing parameters.

The claim analysis would therefore focus on the overall diffraction pattern and the identity of the solid form, not only on whether one peak appears at an exact decimal value.

Why are the PXRD, TGA, and DSC claims important?

PXRD is the principal tool for polymorph identification. TGA can indicate solvent or water loss and thermal stability. DSC can show melting, desolvation, or solid-solid transitions.

For enforcement, PXRD is likely to provide the most direct comparison. TGA and DSC can corroborate identity but may be less discriminating if multiple forms have similar thermal behavior.

What is the scope of claim 1 compared with the dependent claims?

Claim 1 is the broadest product claim in the patent. Claims 2 through 8 narrow the claim set by adding analytical characteristics.

A practical hierarchy is:

1. Claim 1: alpha crystalline eluxadoline.
2. Claims 2 to 4: alpha crystal identified by selected PXRD peaks.
3. Claims 5 and 6: alpha crystal identified by a fuller PXRD pattern.
4. Claims 7 and 8: alpha crystal supported by TGA or DSC characteristics.
5. Claim 9: therapeutic administration of the alpha crystal.

The dependent claims are useful for infringement proof and validity defense. They may also face different prior-art risks. A prior-art reference that discloses the same alpha form could threaten claim 1 even if it does not reproduce every analytical figure. Claims containing the more specific pattern limitations may survive if the prior art does not disclose the claimed combination.

When does U.S. Patent 8,691,860 lose exclusivity?

The ordinary patent term appears to run from the earliest relevant nonprovisional or international filing in the 2009 priority chain, placing the nominal expiration around June 2029. The operative expiration should be confirmed against the USPTO patent-term calculation and the FDA Orange Book listing because patent-term adjustment can extend the date.[2][3]

Exclusivity timeline

Event	Date or period
Earliest identified priority	2009
Patent grant	April 8, 2014
FDA approval of Viberzi	May 27, 2015
New chemical entity exclusivity	Approximately through May 27, 2020
Nominal patent expiry	Approximately June 2029
Potential generic entry	Before expiry only if an ANDA applicant prevails, settles on an authorized date, or avoids the listed patents

NCE exclusivity expired before the expected patent term. The commercial barrier therefore shifted from FDA regulatory exclusivity to listed patent protection.

What is the Orange Book status of U.S. Patent 8,691,860?

U.S. Patent 8,691,860 has been associated with Viberzi and the eluxadoline NDA in FDA patent-listing materials. Orange Book listing is significant because it requires an ANDA applicant to address the listed patent through one of four certifications:

• Paragraph I: No required patent information has been filed;
• 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.

A Paragraph IV certification can trigger patent litigation if the NDA holder or patent owner files suit within the statutory period. A timely suit can create a 30-month stay of ANDA approval, subject to statutory exceptions and court action.[2]

The Orange Book listing does not itself establish validity or infringement. It determines the regulatory pathway and creates a mechanism for patent litigation.

Which companies are challenging the Viberzi patent estate?

Publicly identifying a challenger requires matching an ANDA, Paragraph IV notice, litigation docket, and FDA regulatory record. The supplied claim set alone does not establish that a specific company has filed a Paragraph IV challenge to U.S. Patent 8,691,860.

The principal potential challengers would be generic manufacturers seeking approval for eluxadoline tablets. Their likely strategies include:

Strategy	Patent consequence
Paragraph III certification	Entry delayed until patent expiry
Paragraph IV certification	Immediate litigation risk and possible 30-month stay
Non-infringement through another polymorph	Requires proof that the commercial API is not alpha crystal
Invalidity challenge	Could target anticipation, obviousness, written description, enablement, or indefiniteness
Formulation redesign	May avoid formulation claims but not necessarily an API polymorph claim
ANDA product using alpha crystal	Highest direct infringement risk under claim 1

No biosimilar pathway applies. Eluxadoline is a small-molecule drug, so competition would proceed through the ANDA framework rather than a biosimilar application under the Public Health Service Act.

What validity issues affect the alpha-crystal patent?

Anticipation

An anticipation challenge would require a single prior-art reference to disclose the claimed alpha crystal, directly or inherently, with sufficient identifying information. A reference that discloses only eluxadoline generally may not anticipate a specific polymorph.

Obviousness

Obviousness is the principal technical risk for a polymorph patent. Generic or other challengers could argue that a skilled formulator would have screened eluxadoline for crystalline forms and would have expected to identify the alpha form.

The patent owner would likely rely on evidence such as:

• Unexpected stability;
• Improved crystallinity;
• Better filtration or drying;
• Controlled particle properties;
• Reduced hygroscopicity;
• Improved manufacturing consistency;
• Unexpected thermal behavior;
• Superior pharmaceutical performance.

The strength of that defense depends on what the patent specification and prosecution record demonstrate.

Written description and enablement

The specification appears to identify the alpha form through analytical data and preparation methods. The key issue would be whether the disclosure adequately enables production and identification of the full scope of the claimed crystal rather than only one laboratory sample.

Claim construction

Potential disputes include:

• The meaning of “Form alpha”;
• The tolerance permitted by “about”;
• The scope of “substantially similar”;
• Whether a sample can satisfy claim 1 without satisfying the narrower PXRD claims;
• Whether a mixture containing alpha crystal infringes;
• Whether conversion during manufacturing or storage is sufficient.

What manufacturing and formulation barriers does the patent create?

The patent creates a meaningful API-level barrier because a generic manufacturer cannot assume that changing tablet excipients will avoid the patent. If the generic uses the same alpha crystalline API, the tablet may still implicate claim 1.

A non-infringing development program could investigate:

• A different crystalline polymorph;
• An amorphous dispersion;
• A salt form;
• A hydrate or solvate;
• A co-crystal;
• A formulation that converts the alpha crystal before administration.

Each path carries technical and regulatory risk. A different solid form may have different dissolution, stability, bioavailability, particle-size, and manufacturing characteristics. FDA bioequivalence requirements may limit the commercial value of a technically distinct form even if it avoids literal infringement.[4]

What patent landscape surrounds U.S. Patent 8,691,860?

The eluxadoline estate should be analyzed in layers rather than as a single patent.

Estate layer	Typical protection	Relevance to generic entry
Core molecule	Eluxadoline compound claims	May have expired earlier or be separate from the polymorph patent
Alpha polymorph	U.S. 8,691,860	Direct API solid-state barrier
Manufacturing	Crystallization, isolation, purification, or solid-form processes	Can block production routes
Formulation	Tablet composition, release, stability, or dosage form	Can create additional infringement exposure
Method of use	IBS, IBS-D, pain, opioid-receptor disorders	Relevant to label and induced infringement
Regulatory listing	Orange Book patents tied to NDA 206940	Determines ANDA certifications and litigation exposure

The practical freedom-to-operate question is not whether a generic avoids U.S. Patent 8,691,860 alone. It is whether the proposed API, manufacturing process, tablet, labeling, and commercial use avoid the entire live patent estate.

How strong is the patent estate for Viberzi?

The estate is strongest against a generic that uses the same alpha crystalline eluxadoline and seeks the same IBS-D indication. That product would face:

• Direct exposure under claim 1;
• Potential exposure under claims 2 through 8 depending on analytical data;
• Method-of-treatment exposure under claim 9;
• Possible additional Orange Book-listed patents covering formulation or use.

The estate is weaker against a challenger that develops and validates a distinct polymorph, uses a non-infringing manufacturing process, and adopts a label that avoids patented methods of use. That strategy is technically expensive and may still face bioequivalence and product-quality obstacles.

What generic launch scenarios exist?

Launch after patent expiry

This is the lowest-risk scenario. The generic waits until the listed patent term ends and files or maintains a Paragraph III position.

Paragraph IV launch

A challenger files a Paragraph IV certification and either defeats the patent, obtains a favorable settlement date, or accepts litigation risk. The expected launch date depends on the validity and infringement case, regulatory stay periods, and settlement terms.

At-risk launch

A generic launches before final resolution. This can expose the applicant to damages, an injunction, and potential loss of market access. At-risk entry is less attractive where the patented polymorph is the commercial API and laboratory testing can readily identify infringement.

Design-around launch

The applicant develops another solid form. This avoids the most direct claim 1 theory but requires a complete analytical and regulatory package. It may also trigger separate patent claims if the alternative form was later patented.

What licensing deals affect eluxadoline?

Eluxadoline was developed by Furiex Pharmaceuticals and later commercialized through the Forest Laboratories, Actavis, Allergan, and AbbVie corporate chain. These transactions affect ownership and commercialization history, but corporate succession does not change the technical scope of U.S. Patent 8,691,860.

A license or acquisition must be reviewed through assignment records, SEC filings, transaction agreements, and any recorded exclusive-license documents. Patent ownership and NDA sponsorship should be checked separately because the patent owner, exclusive licensee, and NDA holder may not be the same legal entity.

Key Takeaways

• U.S. Patent 8,691,860 protects the Form alpha crystalline form of eluxadoline.
• Claim 1 is the principal API claim.
• Claims 2 through 8 identify the alpha form through PXRD, TGA, and DSC characteristics.
• Claim 9 covers treatment using the alpha crystal for IBS, pain, and other opioid-receptor disorders.
• The patent is associated with Viberzi, FDA NDA 206940.
• The expected nominal patent expiry is approximately June 2029, subject to patent-term adjustment and current Orange Book data.
• The patent does not broadly cover every form of eluxadoline.
• A generic using the same alpha crystal faces direct infringement risk even if it changes excipients or tablet design.
• A polymorph or amorphous-form design-around is possible in principle but creates substantial technical, bioequivalence, manufacturing, and regulatory risk.
• No biosimilar pathway applies because eluxadoline is a small-molecule drug.
• A complete entry analysis requires review of the entire Orange Book-listed estate, not U.S. Patent 8,691,860 in isolation.

FAQs About U.S. Patent 8,691,860 and Eluxadoline

Does U.S. Patent 8,691,860 cover Viberzi tablets?

It can cover the alpha crystalline eluxadoline API used in Viberzi tablets. The patent does not, based on the supplied claims, require a particular tablet composition or strength.

Can a generic avoid the patent by using a different polymorph?

Potentially. A genuinely different polymorph may avoid literal infringement of the alpha-crystal claims, but the generic must establish that its API does not contain the claimed alpha form in an infringing amount or combination.

Is claim 9 limited to IBS-D?

Claim 9 recites irritable bowel syndrome generally, along with pain and other opioid-receptor disorders. FDA approval for Viberzi is narrower and focuses on IBS-D. Patent scope and approved-label scope are separate issues.

Does the patent cover eluxadoline salts or solvates?

The supplied claims identify the alpha crystal of the specified eluxadoline compound and do not expressly recite a salt, hydrate, or solvate. Whether a particular derivative falls within the claims depends on its chemical and solid-state identity.

Is U.S. Patent 8,691,860 a biologic exclusivity patent?

No. It is a small-molecule pharmaceutical patent. Generic competition would use the ANDA pathway rather than the biosimilar pathway.

References

1. U.S. Food and Drug Administration. (2015). Viberzi (eluxadoline) prescribing information.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,691,860: Crystalline form of eluxadoline.
4. U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Patent certifications and approval requirements.

Drugs Protected by US Patent 8,691,860

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Abbvie	VIBERZI	eluxadoline	TABLET;ORAL	206940-001	May 27, 2015		RX	Yes	No	8,691,860			Y		TREATMENT OF IRRITABLE BOWEL SYNDROME WITH DIARRHEA (IBS-D) WITH VIBERZI (ELUXADOLINE).
Abbvie	VIBERZI	eluxadoline	TABLET;ORAL	206940-002	May 27, 2015		RX	Yes	Yes	8,691,860			Y		TREATMENT OF IRRITABLE BOWEL SYNDROME WITH DIARRHEA (IBS-D) WITH VIBERZI (ELUXADOLINE).

International Family Members for US Patent 8,691,860

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2176234		122017000010	Germany
European Patent Office	2176234		132017000028056	Italy
European Patent Office	2176234		17C1005	France
European Patent Office	2176234		C02176234/01	Switzerland
European Patent Office	2176234		SPC/GB17/019	United Kingdom