Details for Patent: 7,214,696

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Which drugs does patent 7,214,696 protect, and when does it expire?

Patent 7,214,696 protects VYNDAMAX and VYNDAQEL and is included in two NDAs.

This patent has thirty-five patent family members in seventeen countries.

Summary for Patent: 7,214,696

Title:	Compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding
Abstract:	Kinetic stabilization of the native state of transthyretin is an effective mechanism for preventing protein misfolding. Because transthyretin misfolding plays an important role in transthyretin amyloid diseases, inhibiting such misfolding can be used as an effective treatment or prophylaxis for such diseases. Treatment methods, screening methods, as well as specific transthyretin stabilizing compounds are disclosed.
Inventor(s):	Jeffery W. Kelly, Yoshiki Sekijima
Assignee:	Scripps Research Institute
Application Number:	US11/256,026
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,214,696
Patent Claim Types: see list of patent claims	Use;

US Patent 7,214,696: Tafamidis Claim Scope, Expiration, Orange Book Status and Patent Landscape

US Patent 7,214,696 covers methods of treating transthyretin amyloidosis with substituted 2-aryl-benzoxazole compounds, including tafamidis, the active ingredient in Vyndaqel and Vyndamax. Its principal commercial claim is directed to administering 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole, now known as tafamidis, to treat transthyretin amyloid disease. The patent’s earliest priority date is October 16, 2002, producing an ordinary U.S. patent term that ended in October 2023, subject to any applicable patent-term adjustment or terminal disclaimer shown in the USPTO record. The patent is therefore no longer the primary U.S. barrier to generic tafamidis entry.

What does US Patent 7,214,696 protect?

US 7,214,696 protects a treatment method rather than a composition of matter, formulation, manufacturing process, or specific dosage regimen. The independent claim requires:

1. A subject in need of treatment;
2. A transthyretin amyloid disease;
3. Administration of a therapeutically effective amount;
4. A compound within the claimed substituted benzoxazole genus; and
5. The compound or a pharmaceutically acceptable salt.

The claimed compounds contain a benzoxazole core with:

• A carboxy substituent at the 4, 5, 6, or 7 position; and
• A phenyl group at the 2 position;
• The phenyl group is unsubstituted, difluoro-substituted, dichloro-substituted, or trifluoromethyl-substituted in specified arrangements.

The patent does not, based on the supplied claims, require a particular dosage, route of administration, treatment duration, disease stage, transthyretin mutation, biomarker, or formulation.

What is the commercial compound covered by the patent?

The key compound is:

Patent nomenclature	Commercial name	Drug product
6-Carboxy-2-(3,5-dichlorophenyl)-benzoxazole	Tafamidis free acid	Vyndamax
Tafamidis meglumine	Tafamidis meglumine salt	Vyndaqel

Claim 3 expressly recites 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole. Claims 6, 9, and 12 apply that compound to familial amyloid polyneuropathy, familial amyloid cardiomyopathy, and senile systemic amyloidosis, respectively.

The patent claims the free-acid compound and pharmaceutically acceptable salts. That language is important because it reaches salt forms used in pharmaceutical products, although the precise scope can depend on claim construction, salt identity, written-description support, and the prosecution history.

How many compounds are covered by the claims?

Claim 2 recites 28 specifically named compounds. It combines four possible carboxy positions with seven aryl substituent patterns:

Carboxy position	Number of aryl variants	Examples
4-position	7	Difluoro, dichloro, trifluoromethyl, or phenyl variants
5-position	7	Same aryl pattern set
6-position	7	Same aryl pattern set
7-position	7	Same aryl pattern set
Total	28	Named compounds in claim 2

The dependent claims then narrow the genus into disease-specific and compound-specific combinations.

The supplied claim set includes:

• Claim 1: Broad treatment method using the formula-defined genus.
• Claim 2: The 28 named benzoxazole compounds.
• Claims 3 and 16: Specific compounds, including tafamidis.
• Claims 4-15 and 17-20: Disease-specific limitations.
• Claims 21-46: Individual compounds, largely repeating compounds already identified in claim 2.

The formula drawing referenced in claim 1 is not included in the supplied text. The full scope of claim 1 therefore depends on the formula and definitions appearing in the issued patent. The named compounds in claims 2-46 provide the clearest basis for assessing commercial coverage.

Does US 7,214,696 cover tafamidis?

Yes. The patent directly covers tafamidis treatment methods.

Tafamidis is 6-carboxy-2-(3,5-dichlorophenyl)-1,3-benzoxazole. It is expressly recited in claim 3. Claims 6, 9, and 12 further specify treatment of particular transthyretin amyloid diseases with that compound.

The practical claim set is therefore stronger than a purely generic genus claim. Even if a competitor challenged the broader formula or the written-description support for the genus, the express recitation of tafamidis provides a direct claim to the commercially relevant molecule and its use in several ATTR disease settings.

What diseases are covered by US Patent 7,214,696?

The claims identify four principal disease categories:

Disease in the claims	Relevant claim groups	Commercial relevance
Familial amyloid polyneuropathy	Claims 4-6, 17	Original Vyndaqel indication
Familial amyloid cardiomyopathy	Claims 7-9, 18	ATTR cardiac disease
Senile systemic amyloidosis	Claims 10-12, 19	Now generally referred to as wild-type ATTR amyloidosis
Cardiac amyloidosis following liver transplantation	Claims 13-15, 20	Specific post-transplant disease setting

The use of “senile systemic amyloidosis” reflects terminology used when the patent was drafted. Current clinical and regulatory terminology more commonly uses “wild-type transthyretin amyloidosis” or “wild-type ATTR,” particularly for cardiomyopathy.

The patent’s disease language is broad enough to encompass transthyretin amyloid pathology in both hereditary and nonhereditary settings, but the claim must still be applied to the specific disease limitations recited in each dependent claim.

What is the legal scope of the method claims?

The claims require actual administration. A party generally would not infringe merely by manufacturing or selling a compound unless its conduct falls within another asserted claim or an inducement or contributory-infringement theory.

Potential infringement scenarios include:

• Administering tafamidis to patients with ATTR polyneuropathy;
• Administering tafamidis to patients with ATTR cardiomyopathy;
• Labeling a product for a claimed transthyretin amyloid disease;
• Encouraging or instructing healthcare professionals to use the drug for a claimed indication;
• Selling a product with instructions that specifically promote a claimed use.

The claims do not expressly require:

• Tafamidis meglumine rather than tafamidis free acid;
• A particular tablet strength;
• Once-daily dosing;
• Oral administration;
• A specific patient mutation;
• A transthyretin stabilizer biomarker;
• A particular level of TTR tetramer stabilization.

These omissions reduce the patent’s ability to distinguish products based solely on dose, tablet presentation, or ordinary clinical-use parameters.

How could a generic avoid literal infringement?

A generic applicant could seek to avoid the method claims through a label that omits the patented indication, where legally and commercially feasible. That approach is commonly analyzed under the “skinny label” framework for method-of-use patents.

The risk is higher if:

• The approved indication substantially overlaps the claimed disease;
• The proposed label instructs use for ATTR cardiomyopathy or polyneuropathy;
• The product has no substantial noninfringing use;
• Marketing materials encourage the claimed treatment;
• The patent is listed in the FDA Orange Book and triggers a Paragraph IV dispute.

Because US 7,214,696 expired in 2023, these issues now have limited practical significance for this patent itself. They can remain relevant to historical litigation analysis and to later patents with overlapping use claims.

When did US Patent 7,214,696 expire?

The patent’s priority date is October 16, 2002. The patent issued on May 8, 2007. Under the modern U.S. patent-term framework, the basic term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and other term modifiers.

The expected ordinary expiration date was October 16, 2023. The controlling date should be confirmed against the USPTO patent-term data and any terminal disclaimer or patent-term adjustment recorded for the patent. The patent is not a current long-term exclusivity barrier based on its 2002 priority date and its published patent history. (U.S. Patent No. 7,214,696, 2007; USPTO, n.d.)

What was the FDA regulatory status of tafamidis?

The FDA approved Vyndaqel, tafamidis meglumine, in 2011 for delaying the loss of peripheral neurologic function in adults with transthyretin-mediated familial amyloid polyneuropathy. The FDA later approved Vyndaqel and Vyndamax for cardiomyopathy caused by wild-type or hereditary transthyretin-mediated amyloidosis in adults. Vyndamax contains tafamidis free acid, while Vyndaqel contains tafamidis meglumine. (FDA, 2011, 2019a, 2019b)

Product	Active ingredient	FDA approval role
Vyndaqel	Tafamidis meglumine	ATTR polyneuropathy and ATTR cardiomyopathy products
Vyndamax	Tafamidis free acid	ATTR cardiomyopathy
Generic tafamidis	Tafamidis or equivalent salt/form	Subject to ANDA requirements and applicable listed patents

The original orphan-drug exclusivity for the familial amyloid polyneuropathy indication did not replace the patent estate. Orphan exclusivity is indication-specific and time-limited. It does not prevent approval of a product for an indication outside the protected orphan use, and it does not extend the patent term.

What is the Orange Book status of US 7,214,696?

US 7,214,696 was associated with the tafamidis product patent landscape and has been relevant to FDA patent listing and generic-entry analysis. Its legal significance is now limited by expiration.

The Orange Book distinguishes between:

• Patent expiration;
• Patent delisting;
• FDA regulatory exclusivity;
• Active listed patents;
• Paragraph IV certifications.

Expiration does not necessarily mean immediate removal from every historical Orange Book record. The relevant commercial question is whether any unexpired patent remains listed against the specific reference product and whether FDA regulatory exclusivity remains in force. The FDA Orange Book should be used for the current product-specific listing record. (FDA, n.d.)

US 7,214,696 is not a current basis for blocking an ANDA after its patent term has ended. Any present generic-entry analysis must focus on later patents covering tafamidis salts, crystalline forms, formulations, dosing regimens, methods of use, or manufacturing processes.

Which patents are more important after US 7,214,696?

Later tafamidis patents are likely more relevant than the ’696 patent because they may extend beyond 2023. The principal follow-on categories are:

Tafamidis salt and composition patents

These may cover tafamidis meglumine, specific salt stoichiometries, pharmaceutical compositions, or improved physicochemical properties. Such claims can be relevant to Vyndaqel even after the basic compound or method patent expires.

Formulation patents

Formulation claims may cover:

• Tablet composition;
• Excipients;
• Dissolution properties;
• Stability;
• Dosage strength;
• Free-acid versus salt presentation;
• Manufacturing parameters that produce a defined solid form.

Formulation patents usually do not block every tafamidis product. Their effect depends on whether the generic product practices the claimed composition or process.

Method-of-use patents

Later use patents may cover:

• ATTR cardiomyopathy;
• Specific hereditary TTR mutations;
• Wild-type ATTR;
• Neurologic progression;
• Cardiac outcomes;
• Patient-selection criteria;
• Specific dosing or treatment timing.

A generic applicant may challenge such patents through Paragraph IV certification or omit the patented use from its label, depending on the regulatory record.

Manufacturing patents

Process patents can cover synthesis intermediates, reaction conditions, purification, crystallization, or salt formation. They can create supply-chain constraints without preventing all independent manufacture of tafamidis.

Are biosimilar risks relevant to tafamidis?

No. Tafamidis is a small-molecule drug, not a biologic. The relevant U.S. pathway is an abbreviated new drug application, not a biosimilar application under the Public Health Service Act.

The commercial threats are therefore:

• Generic tafamidis;
• Generic tafamidis meglumine;
• Alternative tafamidis formulations;
• Competing transthyretin stabilizers;
• TTR gene-silencing therapies;
• TTR gene-editing approaches.

Biosimilar litigation is not the appropriate framework for this product.

Which companies could challenge tafamidis exclusivity?

The public commercial landscape includes potential generic manufacturers with experience in complex small-molecule ANDA filings, but a company should not be treated as an active challenger without a filed ANDA, Paragraph IV notice, FDA litigation record, or court docket.

The relevant challenger categories are:

• Large generic companies;
• Specialty generic manufacturers;
• Companies pursuing 505(b)(2) products;
• Contract manufacturers supplying an ANDA sponsor.

The expiration of US 7,214,696 removes the need to challenge that patent prospectively. Any current Paragraph IV activity would be directed to later unexpired patents listed for Vyndaqel or Vyndamax.

How strong is the patent estate for tafamidis?

The ’696 patent was commercially strong during its term because it combined:

• An express tafamidis claim;
• Broad substituted benzoxazole coverage;
• Disease-specific dependent claims;
• Coverage of hereditary and nonhereditary ATTR conditions;
• Coverage of pharmaceutically acceptable salts.

Its present strength is low because the expected patent term ended in 2023. The remaining estate’s strength depends on later patents and the extent to which those patents cover the product actually marketed by Pfizer.

Risk category	Assessment for US 7,214,696
Coverage of tafamidis	Direct and explicit
Coverage of tafamidis salt	Supported by salt language, subject to construction
Coverage of ATTR polyneuropathy	Express
Coverage of ATTR cardiomyopathy	Express
Coverage of formulation	None apparent from supplied claims
Coverage of manufacturing process	None apparent from supplied claims
Dose-specific coverage	None apparent
Current blocking power	Low after expiration
Historical litigation value	High
Current generic-entry relevance	Limited

What is the likely generic launch scenario?

A generic launch analysis should separate three scenarios:

1. Paragraph III launch: The applicant accepts later patent expiration and launches after the last blocking patent expires.
2. Paragraph IV launch: The applicant challenges one or more unexpired listed patents and seeks approval before their expiration.
3. Skinny-label launch: The applicant omits protected indications or uses, if the remaining patent claims permit a legally adequate carve-out.

US 7,214,696 would not by itself support a current Paragraph IV barrier after expiration. The decisive issues are the status of later Orange Book-listed patents, regulatory exclusivity, the proposed generic label, and the product’s formulation or salt form.

What geographic coverage does the patent provide?

US 7,214,696 provides rights only in the United States. Corresponding international applications or national-stage patents may have existed, but a U.S. patent cannot establish infringement liability in Europe, Japan, China, or other jurisdictions.

International analysis requires separate review of:

• Patent family members;
• National grant and lapse status;
• Patent-term adjustments or supplementary protection certificates;
• Local claim scope;
• Local regulatory exclusivity;
• Local litigation and settlement agreements.

The compound and method may have been protected through related foreign patent families, but U.S. expiration does not determine foreign expiration.

Key Takeaways

• US 7,214,696 is a method-of-treatment patent for transthyretin amyloidosis.
• It expressly covers tafamidis, chemically identified as 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole.
• The claims cover familial amyloid polyneuropathy, familial amyloid cardiomyopathy, senile systemic amyloidosis, and post-liver-transplant cardiac amyloidosis.
• Claim 2 names 28 substituted benzoxazole compounds.
• The patent contains no apparent formulation, manufacturing, dosage, or route-specific claims in the supplied claim set.
• The patent’s expected term ended in October 2023, subject to the controlling USPTO term record.
• Current generic risk depends on later tafamidis patents, not primarily on US 7,214,696.
• Tafamidis is a small molecule, so generic ANDA analysis applies; biosimilar analysis does not.
• The FDA Orange Book and USPTO records remain the controlling sources for current listed-patent and term status.

Frequently Asked Questions

Is tafamidis itself claimed in US Patent 7,214,696?

Yes. Claim 3 expressly identifies 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole, the chemical entity known as tafamidis.

Does US 7,214,696 cover Vyndaqel?

Yes, the claims cover tafamidis and pharmaceutically acceptable salts administered to treat specified transthyretin amyloid diseases. Vyndaqel contains tafamidis meglumine.

Does US 7,214,696 cover Vyndamax?

Yes, the patent expressly covers tafamidis free acid, the active ingredient in Vyndamax, when used for a claimed transthyretin amyloid disease.

Can a generic launch after the ’696 patent expires?

Expiration of the ’696 patent removes that patent as a blocking right. Launch timing still depends on later listed patents, regulatory exclusivity, FDA approval requirements, and any litigation involving those later patents.

Is tafamidis protected by a biosimilar patent strategy?

No. Tafamidis is a small molecule. Its U.S. competition is governed primarily by ANDA, Orange Book, Paragraph IV, formulation, salt, method-of-use, and manufacturing-patent issues.

References

1. Food and Drug Administration. (2011). Vyndaqel (tafamidis meglumine) prescribing information. U.S. Department of Health and Human Services.

2. Food and Drug Administration. (2019a). Vyndaqel (tafamidis meglumine) prescribing information. U.S. Department of Health and Human Services.

3. Food and Drug Administration. (2019b). Vyndamax (tafamidis) prescribing information. U.S. Department of Health and Human Services.

4. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.

5. U.S. Patent No. 7,214,696. (2007). Methods for treating transthyretin amyloidosis. United States Patent and Trademark Office.

6. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. U.S. Department of Commerce.

Drugs Protected by US Patent 7,214,696

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Foldrx Pharms	VYNDAMAX	tafamidis	CAPSULE;ORAL	212161-001	May 3, 2019		RX	Yes	Yes						TREATMENT OF THE CARDIOMYOPATHY OF WILD TYPE OR HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS (ATTR-CM)
Foldrx Pharms	VYNDAQEL	tafamidis meglumine	CAPSULE;ORAL	211996-001	May 3, 2019		DISCN	Yes	No						TREATMENT OF THE CARDIOMYOPATHY OF WILD TYPE OR HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS (ATTR-CM)

International Family Members for US Patent 7,214,696

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1587821		C300516	Netherlands
European Patent Office	1587821		91935	Luxembourg
European Patent Office	1587821		C20120001 00050	Estonia