Details for Patent: 9,770,441

Which drugs does patent 9,770,441 protect, and when does it expire?

Patent 9,770,441 protects VYNDAMAX and is included in one NDA.

This patent has thirty-one patent family members in twenty-two countries.

Summary for Patent: 9,770,441

Title:	Crystalline solid forms of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole
Abstract:	The present invention relates to solid forms of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole and to methods for their preparation. The invention is also directed to pharmaceutical compositions containing at least one solid form and to the therapeutic or prophylactic use of such solid forms and compositions.
Inventor(s):	Kevin Paul Girard, Andrew J. Jensen, Kris Nicole Jones
Assignee:	Pfizer Corp SRL
Application Number:	US15/509,343
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,770,441
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 9,770,441: Tafamidis Crystalline-Form Claims, Exclusivity, Litigation and Generic-Entry Analysis

US Patent 9,770,441 protects specific crystalline forms of tafamidis, chemically identified as 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole. The patent is a solid-state and manufacturing barrier rather than a broad protection for the tafamidis molecule itself. Its independent claims are defined by analytical signatures, including powder X-ray diffraction, solid-state carbon-13 NMR, and Raman spectroscopy.

The patent has commercial relevance to Pfizer’s tafamidis products, including Vyndaqel and Vyndamax, because a generic or alternative manufacturer may need to produce tafamidis in a different solid form, use a noninfringing salt or formulation, or challenge the patent under Paragraph IV.

What drug and chemical entity does US 9,770,441 cover?

The claimed compound is tafamidis in its free-acid form:

Attribute	Information
Drug substance	Tafamidis
Chemical name	6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole
Therapeutic class	Transthyretin stabilizer
Principal products	Vyndaqel and Vyndamax
Sponsor	Pfizer
Primary diseases	Transthyretin amyloid polyneuropathy and cardiomyopathy
Patent type	Crystalline-form and product-by-process-adjacent solid-state protection
Patent	US 9,770,441
Grant date	September 26, 2017
Nominal term basis	Twenty years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and other statutory modifications

Tafamidis binds transthyretin and stabilizes the thyroxine-binding tetramer. Vyndaqel contains tafamidis meglumine, while Vyndamax contains tafamidis as the free acid. The distinction matters because US 9,770,441 claims crystalline tafamidis free acid, not every possible tafamidis salt, solvate, amorphous form, or pharmaceutical formulation.

The patent is directed to a solid-state form of the active pharmaceutical ingredient. It does not broadly claim the pharmacological mechanism of transthyretin stabilization or all methods of treating transthyretin amyloid disease.

What are the independent claims in US 9,770,441?

Claims 1, 11, 12, 15 and 16 are the principal independent or independently structured claims.

Claim	Subject matter	Practical scope
1	Crystalline tafamidis identified by at least one listed analytical parameter	Broadest product claim
11	Crystalline tafamidis defined by PXRD peaks at 26.7° and 28.6° plus a solid-state NMR shift at 127.7 ppm	Multimodal solid-form claim
12	Crystalline tafamidis defined by Raman peaks at 1292 and 1615 cm⁻¹ plus a solid-state NMR shift at 127.7 ppm	Multimodal solid-form claim
15	Pharmaceutical composition containing the crystalline form of claim 1	Composition claim
16	Treatment of transthyretin amyloid disease using the crystalline form of claim 1	Method-of-use claim

Claim 1 is the commercial center of the patent. It covers a crystalline form having an analytical parameter selected from three alternatives:

1. Solid-state NMR chemical shifts at 120.8 ± 0.2 ppm and 127.7 ± 0.2 ppm.
2. A PXRD peak at 28.6 ± 0.2 degrees 2θ.
3. A Raman peak at 1292 ± 2 cm⁻¹.

The use of “selected from the group consisting of” means that, on its face, claim 1 can be satisfied by any one of the listed analytical alternatives. A product does not necessarily need to show all three types of analytical data to fall within claim 1.

That drafting structure gives claim 1 substantial reach, but it also creates claim-construction and validity issues. A court would likely examine the specification, the disclosed polymorph, the analytical methods, and whether the listed parameter is sufficiently tied to one identifiable crystalline form.

How do claims 2 through 14 narrow the crystalline-form protection?

Claims 2 through 14 add analytical markers or physical characteristics. They create fallback positions if claim 1 is narrowed or invalidated.

Solid-state NMR claims

Claims 2 and 3 add further carbon-13 chemical shifts:

• Claim 2 adds 139.6 ± 0.2 ppm.
• Claim 3 adds 144.7 ± 0.2 ppm.

These claims require the form to exhibit the additional shift together with the claim 1 NMR limitations. They provide narrower protection against a producer whose material is analytically close to the disclosed form but whose testing does not satisfy every PXRD or Raman limitation.

PXRD claims

Claim 4 adds PXRD peaks at:

• 16.5 ± 0.2 degrees 2θ
• 26.7 ± 0.2 degrees 2θ

Claims 5 through 7 define another narrower PXRD pattern:

• Claim 5 adds 15.4 ± 0.2 and 20.2 ± 0.2 degrees.
• Claim 6 adds 29.0 ± 0.2 degrees.
• Claim 7 adds 23.5 ± 0.2 degrees.

These claims are valuable for solid-form identification because PXRD is widely used for batch release, polymorph characterization and infringement testing. A generic manufacturer could attempt to avoid these claims by producing a different polymorph, amorphous material, solvate, hydrate or salt. That design-around would need to be stable, reproducible and suitable for regulatory approval.

Raman claims

Claims 8 through 10 add Raman markers:

• Claim 8: 994 ± 2, 1273 ± 2 and 1615 ± 2 cm⁻¹.
• Claim 9: 287 ± 2 and 869 ± 2 cm⁻¹.
• Claim 10: 213 ± 2 cm⁻¹.

Raman spectroscopy can be used as a complementary identity test. These claims make it harder to distinguish a noninfringing form merely by relying on a single PXRD peak. The claims also provide alternative analytical routes for proving infringement.

Physical-property claims

Claims 13 and 14 add:

• Non-hygroscopic and anhydrous characteristics.
• Substantial purity.

These limitations may narrow the claims materially. “Non-hygroscopic,” “anhydrous” and “substantially pure” generally require interpretation against the patent specification and technical evidence. They can create proof disputes if the accused product absorbs limited moisture, contains trace solvates or falls near the purity threshold.

What formulations are protected by US 9,770,441?

Claim 15 covers a pharmaceutical composition containing the claimed crystalline tafamidis form in a therapeutically effective amount with at least one pharmaceutically acceptable excipient.

The claim can reach products such as capsules, tablets or other oral dosage forms if the dosage form contains the patented crystalline free acid. It does not expressly require a particular excipient, dose, capsule shell or release profile.

The claim does not automatically cover every tafamidis formulation. A formulation containing tafamidis meglumine, a different tafamidis crystal form, an amorphous form or a chemically modified derivative may fall outside claim 15, depending on the product’s actual solid-state identity.

The patent therefore has greater relevance to free-acid products, including Vyndamax-type products, than to products that contain only a distinct tafamidis salt. A salt product could still create infringement risk if the manufacturing process or final dosage form contains the claimed crystalline free acid before conversion or if the product otherwise satisfies the claim limitations.

What method-of-use protection does claim 16 provide?

Claim 16 covers administering the claimed crystalline form to treat transthyretin amyloid disease in a mammal.

The disease language is broad relative to a narrow indication. It can encompass transthyretin amyloid polyneuropathy and transthyretin amyloid cardiomyopathy, subject to claim construction and the scope of the specification.

The claim requires use of the claimed crystalline form. It is not simply a claim to treating any transthyretin disease with any tafamidis product. A generic applicant could attempt to avoid direct infringement by using a different crystalline form or a different salt. That strategy may still face direct product-claim risk under claim 1 or claim 15 if the proposed active ingredient satisfies the analytical limitations.

For FDA approval, a method claim can remain commercially relevant even where a generic applicant omits the patented indication through a section viii carve-out. The practical value depends on the approved labeling, the remaining non-patented indications and the extent to which physicians prescribe the product for the patented use.

When does US 9,770,441 expire?

The patent has a nominal expiration date in 2032 based on its priority and filing chronology. The precise enforceable term must be determined from the USPTO patent record, including any patent-term adjustment, terminal disclaimer or other term event.

Event	Timing
Earliest relevant priority period	2011
US patent application period	Early 2010s
Grant of US 9,770,441	September 26, 2017
Nominal expiration	2032
Practical generic-entry date	Potentially before expiration through Paragraph IV litigation or settlement

The 2032 term is separate from FDA regulatory exclusivity. Orphan-drug exclusivity and new-chemical-entity exclusivity do not extend the patent term. Conversely, expiration of regulatory exclusivity does not eliminate an unexpired patent.

What is the Orange Book status of US 9,770,441?

The Orange Book status must be assessed separately for each tafamidis NDA and strength. FDA Orange Book listings identify patents submitted by the NDA holder and may distinguish drug-substance, drug-product and method-of-use patents.

US 9,770,441 is commercially relevant to tafamidis because it claims a crystalline active ingredient and compositions containing that form. Its listing value depends on whether FDA accepted it for the relevant NDA and whether the listed claims are tied to the approved product.

A listing does not establish validity or infringement. It gives the patent holder a statutory basis to receive a Paragraph IV notice and, if suit is filed within the statutory period, obtain an automatic 30-month stay of approval under the Hatch-Waxman framework.

The key regulatory questions are:

Question	Relevance
Is the patent listed against Vyndaqel, Vyndamax or both?	Determines which ANDA products face the patent
Is the listing for the drug substance, drug product or method of use?	Determines the Paragraph IV certification exposure
Does the generic applicant use tafamidis free acid or a salt?	Determines technical infringement risk
Does the applicant carve out an indication?	Determines method-of-use exposure
Was a Paragraph IV notice sent?	Determines litigation and approval timing

What Paragraph IV challenges and litigation affect tafamidis?

A Paragraph IV applicant would typically challenge US 9,770,441 on one or more of four grounds:

1. Noninfringement: the proposed product is not the claimed crystalline form.
2. Anticipation: the claimed form or analytical characteristics were disclosed in prior art.
3. Obviousness: the claimed form was an obvious polymorph-screening result.
4. Written description or enablement: the claim covers more solid forms or analytical variants than the specification adequately supports.

The strongest technical defense for a generic applicant would usually be a well-characterized alternative form. The applicant could submit PXRD, Raman and solid-state NMR data showing that its material lacks the claimed combination of markers.

The strongest patent-holder position would focus on:

• Analytical equivalence of the generic material to the patented form.
• Inherent presence of the claimed peaks or shifts.
• Conversion of an alternative form into the patented form during manufacture or storage.
• Equivalence between the claimed free acid and the active material used in the dosage form.
• Induced or contributory infringement based on instructions for treating transthyretin amyloid disease.

A litigation search should cover the USPTO Patent Center, PACER, FDA Paragraph IV notices and ANDA litigation records. The supplied patent and claims alone do not establish a filed Paragraph IV case, final judgment, settlement, covenant not to sue or licensed launch date.

How strong is the patent estate for tafamidis?

US 9,770,441 is a focused but meaningful patent. Its strength comes from the difficulty of proving that an accused solid form is different when the product has the same molecular identity, similar processing history and overlapping analytical profile.

Its principal weaknesses are the limits of solid-form claiming:

Strength	Limitation
Covers an active pharmaceutical ingredient form	Does not cover all tafamidis forms
Uses multiple analytical technologies	Analytical results can vary by instrument and method
Includes composition and treatment claims	Dependent on the product containing the claimed form
Extends into the early 2030s	Does not itself establish FDA exclusivity
Creates manufacturing and quality-control risk	Alternative polymorphs may provide design-around routes

The claim 1 alternative structure is potentially broad, but the specification and prosecution history may limit how broadly the analytical parameters can be interpreted. A validity assessment should focus on the cited prior art, examples describing the crystal form, amendments made during prosecution and any examiner objection to indefiniteness or written description.

How does this patent compare with broader tafamidis protection?

Protection category	Typical scope	Relevance to generic entry
Original tafamidis compound patent	Tafamidis molecule and related benzoxazoles	May have expired or be near expiry
Crystalline-form patent	Specific tafamidis polymorph identified by analytical data	Can block use of the commercial crystal form
Formulation patent	Dosage form, excipient system or release profile	Applies only to covered formulations
Method-of-use patent	Treating a specified transthyretin disease	Can be addressed through indication carve-outs
Regulatory exclusivity	FDA approval-based protection	Separate from patent validity and term
Manufacturing patent	Process, crystallization or purification method	May block production even if product claims are avoided

US 9,770,441 is most important when the commercial product uses the patented crystalline free acid. It is less comprehensive than a compound patent and less directly relevant to a product containing only a different tafamidis salt.

What generic launch scenarios exist?

Three launch scenarios are most likely:

Launch after patent expiry

The generic waits until the patent expires and obtains approval without resolving the solid-form dispute. This is the lowest litigation-risk path but delays market entry until the end of the patent term.

Paragraph IV challenge

The generic certifies that the patent is invalid, unenforceable or not infringed. Pfizer may sue within 45 days, potentially triggering a 30-month approval stay. The generic may launch after a judgment, settlement date or expiration of the statutory stay, subject to other patents and exclusivity.

Noninfringing formulation or solid form

The generic develops an alternative polymorph, amorphous form, hydrate, solvate or salt. The applicant must establish pharmaceutical performance, stability and bioequivalence while avoiding the analytical limitations of claims 1 through 14.

The most commercially credible design-around is an alternative solid form that remains stable throughout manufacturing, storage and administration. A form that converts into the patented crystal under normal conditions would carry substantial infringement risk.

What geographic coverage does US 9,770,441 provide?

The patent provides rights only in the United States. Equivalent protection may exist in foreign jurisdictions through the same patent family, but foreign claims, expiration dates, prosecution histories and validity outcomes can differ.

International analysis should review:

• PCT and national-phase filings.
• European Patent Office family members.
• Canadian, Japanese, Chinese and Australian equivalents.
• National patent-term adjustments or supplementary protection certificates.
• Local litigation and opposition records.
• Regulatory approval of tafamidis products in each market.

A US patent does not block manufacture or sale outside the United States unless a corresponding foreign patent is in force.

Key Takeaways

• US 9,770,441 is a crystalline-form patent for tafamidis free acid.
• Claim 1 is the broadest claim and can be satisfied by one of several analytical alternatives.
• Claims 2 through 14 add NMR, PXRD, Raman, anhydrous, non-hygroscopic and purity limitations.
• Claim 15 covers pharmaceutical compositions containing the claimed crystal.
• Claim 16 covers treatment of transthyretin amyloid disease using the claimed form.
• The patent’s nominal term extends into 2032, subject to the official USPTO term calculation.
• A generic applicant’s principal design-around is a distinct and stable tafamidis solid form or salt.
• Orange Book listing, Paragraph IV activity and litigation must be evaluated against the specific tafamidis NDA.
• The patent is a meaningful commercial barrier but does not cover every tafamidis molecule, salt, formulation or crystal form.

FAQs

Does US 9,770,441 cover Vyndaqel?

It may be relevant to Vyndaqel if the approved product or its manufacturing process contains the claimed crystalline tafamidis form. Vyndaqel contains tafamidis meglumine, so the salt and solid-state composition must be analyzed separately from the free-acid claims.

Does US 9,770,441 cover Vyndamax?

The patent is more directly relevant to Vyndamax because Vyndamax contains tafamidis free acid. Infringement depends on whether the product contains the claimed crystalline form and satisfies the relevant analytical limitations.

Can a generic tafamidis product avoid this patent?

Yes, potentially. A generic may use a different polymorph, amorphous form, hydrate, solvate or salt. The alternative must remain distinct under PXRD, Raman and solid-state NMR testing and must meet FDA quality and bioequivalence requirements.

Is crystalline-form patent protection enforceable against a manufacturing process?

Yes. A process can infringe indirectly or directly if it produces, uses or incorporates the claimed crystalline form. Process steps that convert an alternative material into the patented crystal can create additional infringement exposure.

Does FDA exclusivity extend the expiration date of US 9,770,441?

No. FDA orphan-drug, new-chemical-entity and other regulatory exclusivities are separate from the patent term. They can delay approval or restrict marketing without changing the statutory patent expiration date.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,770,441: Crystalline forms of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole.
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. (2019). Vyndamax (tafamidis) prescribing information.
4. U.S. Food and Drug Administration. (2011). Vyndaqel (tafamidis meglumine) prescribing information.
5. United States Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, patent term and patent litigation provisions.

Drugs Protected by US Patent 9,770,441

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	9,770,441		Y	Y		TREATMENT OF THE CARDIOMYOPATHY OF WILD TYPE OR HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS (ATTR-CM)

Foreign Priority and PCT Information for Patent: 9,770,441

PCT Information
PCT Filed	August 31, 2015	PCT Application Number:	PCT/IB2015/056597
PCT Publication Date:	March 17, 2016	PCT Publication Number:	WO2016/038500

International Family Members for US Patent 9,770,441

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	101778
Australia	2015313875
Brazil	112017003421
Canada	2903194
China	106715405