Details for Patent: 7,214,695

Which drugs does patent 7,214,695 protect, and when does it expire?

Patent 7,214,695 protects VYNDAMAX and VYNDAQEL and is included in two NDAs.

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

Summary for Patent: 7,214,695

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, Evan T. Powers, Hossein Razavi
Assignee:	Scripps Research Institute
Application Number:	US10/741,649
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,214,695
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 7,214,695: Tafamidis Compound Claims, Scope, Expiration and Patent Landscape

US Patent 7,214,695 covers a defined class of carboxy-substituted 2-aryl benzoxazoles, including tafamidis, the active ingredient in Vyndaqel and Vyndamax. Its principal commercial claim is claim 3, which covers 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid, commonly known as tafamidis. The patent also claims pharmaceutical compositions containing the covered compounds.

The patent is a compound patent, not a method-of-use, formulation, manufacturing-process, polymorph, or salt-selection patent. Its ordinary United States patent term reached expiration in 2023, subject to any applicable patent-term adjustment or extension reflected in official USPTO or FDA records. The patent therefore no longer provides a current standalone exclusionary barrier unless a separate statutory extension applied.

What compounds does US Patent 7,214,695 protect?

The patent claims a benzoxazole core bearing a carboxylic acid substituent and an aryl group at the 2-position. The aryl group is limited to six expressly identified substitution patterns:

Ar group in claim 1	Substitution pattern
3,5-Difluorophenyl	Two fluorines at positions 3 and 5
2,6-Difluorophenyl	Two fluorines at positions 2 and 6
3,5-Dichlorophenyl	Two chlorines at positions 3 and 5
2,6-Dichlorophenyl	Two chlorines at positions 2 and 6
2-Trifluoromethylphenyl	One CF3 group at position 2
3-Trifluoromethylphenyl	One CF3 group at position 3

The carboxylic acid can occupy the 4-, 5-, 6-, or 7-position of the benzoxazole ring, based on the species claims and the compounds enumerated in claim 2.

The claim architecture is therefore a finite Markush genus rather than an open-ended class of all aryl benzoxazole carboxylic acids.

Which commercial drug is covered by US 7,214,695?

Tafamidis is covered by claim 3:

2-(3,5-Dichlorophenyl)-benzoxazole-6-carboxylic acid.

The compound is also described as 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid. Tafamidis is a transthyretin stabilizer used for transthyretin-mediated amyloidosis.

Pfizer markets tafamidis in the United States under:

Product	Active ingredient	FDA dosage form	Primary use
Vyndaqel	Tafamidis meglumine	Capsules	Cardiomyopathy caused by wild-type or hereditary transthyretin-mediated amyloidosis
Vyndamax	Tafamidis	Capsules	Cardiomyopathy caused by wild-type or hereditary transthyretin-mediated amyloidosis
Vyndaqel	Tafamidis meglumine	Capsules	Neuropathy associated with hereditary transthyretin-mediated amyloidosis in certain markets and labeling contexts

Vyndaqel contains the meglumine salt of tafamidis. The patent’s claim 1 expressly covers pharmaceutically acceptable salts, which gives the compound claims a direct read-through to tafamidis salt products.

How broad is claim 1?

Claim 1 has three principal limitations:

1. A compound with the claimed benzoxazole-carboxylic acid structure.
2. An aryl group selected from six specified fluorinated, chlorinated, or trifluoromethyl-substituted phenyl groups.
3. A pharmaceutically acceptable salt option.

The claim does not cover every substituted phenyl benzoxazole. A competing compound with a 4-fluorophenyl, 3-chlorophenyl, methylphenyl, methoxyphenyl, or unsubstituted phenyl group would not fall within the literal aryl list in claim 1.

The claim also does not, based on the supplied language, cover:

• Benzoxazoles lacking the carboxylic acid;
• Carboxylic acids at positions outside the claimed 4-, 5-, 6-, and 7-position species;
• Alternative heteroaryl groups;
• Benzothiazole analogs;
• Oxazole or imidazole replacements for the benzoxazole core;
• Ester prodrugs, unless they satisfy the claim through an applicable salt or infringement theory;
• Distinct stereochemical or solid-state forms not encompassed by the chemical structure.

Because the formula drawing referenced in claim 1 is not reproduced in the supplied text, the precise attachment points and ring numbering should be confirmed against the issued patent before conducting an infringement opinion. The dependent species claims, however, identify the intended compound series.

What does claim 2 cover?

Claim 2 lists the named compounds corresponding to the combination of:

• Four carboxy positions: 4, 5, 6, and 7; and
• Six aryl substituent patterns.

The resulting set contains 24 intended species.

Carboxy position	Number of aryl variants	Intended species count
4-position	6	6
5-position	6	6
6-position	6	6
7-position	6	6
Total	24	24

Claim 2 appears to contain a drafting artifact at its conclusion, ending with “or.” That wording does not ordinarily enlarge the preceding closed list. The issued patent should control over any transcription of the claim.

What is the relationship between claim 3 and tafamidis?

Claim 3 specifically claims the 6-carboxy, 3,5-dichlorophenyl species:

2-(3,5-Dichlorophenyl)-benzoxazole-6-carboxylic acid.

That is the key commercial species in the patent. Claim 3 is narrower than claim 1 but provides a direct species claim to tafamidis. A valid species claim generally offers stronger enforcement clarity than a broad Markush claim because the accused product can be compared directly with one defined molecular structure.

Claim 3 also supports the composition claims through claims 8 and 9, which cover a pharmaceutical composition containing the claim 3 compound and a composition formulated for single-dose administration.

What do claims 4 through 9 and 33 through 38 protect?

These claims cover pharmaceutical compositions rather than additional molecular structures.

Claims	Subject matter
4	Composition containing a claim 1 compound and pharmaceutically acceptable carrier
5	Claim 4 composition formulated for single-dose administration
6	Composition containing a claim 2 compound and carrier
7	Claim 6 composition formulated for single-dose administration
8	Composition containing the claim 3 compound and carrier
9	Claim 8 composition formulated for single-dose administration
33	Composition containing the claim 20 compound and carrier
34	Claim 33 composition formulated for single-dose administration
35	Composition containing the claim 26 compound and carrier
36	Claim 35 composition formulated for single-dose administration
37	Composition containing the claim 30 compound and carrier
38	Claim 37 composition formulated for single-dose administration

The composition claims require the presence of the claimed active compound and a pharmaceutically acceptable carrier. They do not, based on the supplied text, require:

• A particular capsule shell;
• A particular excipient;
• A particular dissolution profile;
• A particular particle size;
• A particular crystal form;
• A particular dosage strength;
• A particular release profile;
• A specific treatment indication.

“Single dosage administration” is a narrower formulation limitation, but it does not appear to specify a particular unit dose, amount of active ingredient, administration frequency, or delivery technology.

Does US 7,214,695 claim Vyndaqel and Vyndamax formulations?

The patent claims the tafamidis active moiety and pharmaceutically acceptable salts. That provides a strong compound-claim relationship to tafamidis meglumine in Vyndaqel.

The composition claims are broader at the carrier level. They can potentially read on a conventional oral pharmaceutical composition containing tafamidis or a covered salt. They do not appear to require the specific excipient system used in Vyndaqel or Vyndamax.

The patent should not be treated as a complete formulation patent for all commercial tafamidis products. A product may be covered by the compound claims while falling outside a particular composition claim, or it may be subject to later patents directed to dosage forms, salts, crystalline forms, manufacturing processes, or product-specific formulations.

What is the patent expiration date?

US Patent 7,214,695 was issued in 2007. Its ordinary twenty-year patent term was tied to its earliest effective nonprovisional or international filing date, rather than to the issue date. Public patent and FDA records have generally associated the patent with an expiration date in late 2023, commonly reported as November 29, 2023.

Event	Date or status
Patent issued	2007
Principal commercial species	Tafamidis
Ordinary United States term	Expired in late 2023
Commonly reported expiration date	November 29, 2023
Patent type	Compound and composition
Regulatory product relationship	Vyndaqel and Vyndamax
Biosimilar pathway	Not applicable

The legally operative date should be taken from the USPTO patent record and the applicable FDA Orange Book entry. Patent-term adjustment, patent-term extension, terminal disclaimers, and later corrections can affect the final enforceability analysis.

What was the Orange Book status of US 7,214,695?

US 7,214,695 was associated with tafamidis products approved by FDA. Orange Book relevance depends on the specific reference-listed drug, dosage form, strength, and patent listing status.

For a small-molecule product such as tafamidis, Orange Book patents can support:

• An ANDA Paragraph IV challenge;
• A 30-month stay after timely notice and suit;
• A certification that the listed patent has expired;
• A certification that the patent does not claim the proposed generic product or its use.

The patent is not a biologic exclusivity patent and does not create a biosimilar litigation pathway under the Public Health Service Act. Tafamidis generic applicants would use the ANDA framework under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

Are biosimilars relevant to tafamidis?

No. Tafamidis is a chemically synthesized small molecule. The relevant competitors are generic drug applicants, not biosimilar applicants.

The principal regulatory route is an ANDA demonstrating pharmaceutical equivalence and bioequivalence to the relevant reference-listed drug. A 351(k) biosimilar application would not be the normal pathway for tafamidis.

What Paragraph IV risks arise from this patent?

Before expiration, a generic tafamidis applicant could have challenged the patent through a Paragraph IV certification based on:

• Lack of novelty;
• Obviousness;
• Inadequate written description;
• Lack of enablement;
• Non-infringement, particularly if the proposed product used a noncovered compound or salt;
• Invalidity of the composition claims;
• Patent expiration.

For a generic containing tafamidis itself, non-infringement would have been difficult against a valid claim 3 because the active ingredient is the exact named molecule. The more practical validity arguments would have concerned prior art, obviousness, written description, enablement, and the scope of the salt language.

After expiration, the commercial consequence of a Paragraph IV challenge is reduced because the compound patent no longer independently blocks launch. Remaining risk shifts to later patents listed for the applicable tafamidis product, regulatory exclusivity, and any active litigation or settlement restrictions.

What other patent categories matter for tafamidis?

US 7,214,695 is only one part of the relevant tafamidis patent estate. A commercial freedom-to-operate review should separate the following categories:

Patent category	Relevance to tafamidis competition
Core compound patent	Covers tafamidis and specified analogs
Salt patent	May cover tafamidis meglumine or another salt
Crystalline-form patent	May cover a specific solid form
Formulation patent	May cover excipients, release, dosage, or capsule composition
Manufacturing patent	May cover synthetic intermediates or process controls
Method-of-use patent	May cover cardiomyopathy, neuropathy, or dosing regimens
Product-specific patent	May cover Vyndaqel, Vyndamax, or a particular presentation
Patent covering combination therapy	May cover tafamidis with another active agent

The supplied claims do not contain an express therapeutic method-of-use limitation. They also do not expressly claim a synthetic process, intermediate, crystal form, particle-size distribution, or specific clinical dosing regimen.

How strong is the patent estate?

Compound coverage

The compound coverage was commercially strong because claim 3 directly identified tafamidis. A direct species claim generally creates less claim-construction uncertainty than a large genus claim.

Breadth

The genus is moderate in breadth. It covers 24 principal named structures and their pharmaceutically acceptable salts, but only six aryl substitution patterns and four carboxy positions.

Formulation coverage

The formulation claims are broad in carrier language but comparatively thin in technical detail. They may be vulnerable to validity or scope limitations if the specification does not adequately support the full range of carriers and dosage forms.

Regulatory leverage

The patent provided meaningful pre-expiration ANDA leverage because tafamidis itself was within the claim set. That leverage declined materially upon expiration of the core patent.

Current strength

As an expired patent, US 7,214,695 has no ordinary prospective exclusionary force against new commercial entry. Its remaining significance is historical, litigation-related, and relevant to past infringement or damages periods.

What generic launch scenarios existed or remain?

Before expiration

A generic applicant could have faced:

• Paragraph IV litigation;
• A 30-month stay if the listed patent was timely asserted;
• Delayed launch under a settlement;
• A launch after patent invalidation or non-infringement;
• A limited-risk launch based on a different salt, formulation, or product design.

After expiration

The core patent no longer independently prevents launch of a tafamidis product. Competition would still depend on:

• Other unexpired Orange Book patents;
• FDA exclusivity;
• ANDA approval timing;
• Paragraph IV litigation involving later patents;
• Manufacturing scale and supply reliability;
• Market access and reimbursement;
• Whether the generic targets tafamidis meglumine, tafamidis, or a distinct approved presentation.

What manufacturing and intellectual-property barriers remain?

The patent does not claim the manufacturing process in the supplied claims. A competitor could therefore face separate process or intermediate patents even if US 7,214,695 has expired.

Practical manufacturing barriers may include:

• Control of regioselective benzoxazole synthesis;
• Impurity specifications;
• Reproducible formation of the active pharmaceutical ingredient;
• Salt formation and crystallization;
• Stability of the final capsule;
• Qualification of active-ingredient suppliers;
• Bioequivalence of the generic presentation.

These are commercial and technical barriers, not direct limitations established by claims 1 through 38.

What companies challenged tafamidis exclusivity?

The supplied patent claims do not identify litigation parties, ANDA filers, settlement terms, or launch dates. Those matters must be established from PACER, FDA Orange Book records, ANDA litigation notices, and company disclosures. No reliable party-specific litigation conclusion follows from the claim text alone.

Key Takeaways

• US 7,214,695 is a core compound patent for tafamidis and related benzoxazole carboxylic acids.
• Claim 3 directly covers tafamidis: 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid.
• Claim 1 is a finite Markush claim covering six aryl groups, benzoxazole carboxylic acid derivatives, and pharmaceutically acceptable salts.
• Claims 4 through 9 and 33 through 38 cover compositions containing covered compounds, including single-dose formulations.
• The patent does not claim a therapeutic method, manufacturing process, polymorph, or detailed commercial formulation in the supplied claims.
• Tafamidis is a small molecule, so generic ANDA and Paragraph IV procedures apply. Biosimilar procedures do not.
• The patent’s ordinary term expired in late 2023, commonly reported as November 29, 2023.
• Current generic-entry risk depends primarily on later tafamidis patents, FDA exclusivity, litigation, and commercial execution rather than on US 7,214,695 alone.

FAQs

Is tafamidis the same compound as the compound in claim 3 of US 7,214,695?

Yes. Claim 3 identifies 2-(3,5-dichlorophenyl)-benzoxazole-6-carboxylic acid, the compound commonly known as tafamidis.

Does US 7,214,695 cover tafamidis meglumine?

Claim 1 covers the claimed compound and pharmaceutically acceptable salts. Tafamidis meglumine is the meglumine salt of tafamidis and is within the commercial relevance of that language.

Does the patent cover Vyndamax specifically?

The patent covers the tafamidis active ingredient used in Vyndamax. It should not automatically be treated as covering every product-specific formulation or presentation patent associated with Vyndamax.

Can a generic launch after expiration of US 7,214,695?

Expiration removes the core patent as an independent barrier. A generic applicant must still address any later unexpired patents, FDA requirements, regulatory exclusivity, and applicable litigation.

Does the patent protect tafamidis treatment for transthyretin amyloidosis?

The supplied claims do not contain a method-of-use claim. They claim compounds and pharmaceutical compositions. Treatment indications may be covered by separate patents or regulatory exclusivity.

References

1. United States Patent and Trademark Office. (2007). U.S. Patent No. 7,214,695: Benzoxazole compounds. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (2019). Vyndaqel (tafamidis meglumine) prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (2019). Vyndamax (tafamidis) prescribing information. FDA.

5. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.

Drugs Protected by US Patent 7,214,695

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			Y	Y
Foldrx Pharms	VYNDAQEL	tafamidis meglumine	CAPSULE;ORAL	211996-001	May 3, 2019		DISCN	Yes	No			Y	Y

International Family Members for US Patent 7,214,695

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