Details for Patent: 11,578,062

Which drugs does patent 11,578,062 protect, and when does it expire?

Patent 11,578,062 protects TRIKAFTA (COPACKAGED), ALYFTREK, and SYMDEKO (COPACKAGED), and is included in four NDAs.

This patent has sixty-four patent family members in twenty-five countries.

Summary for Patent: 11,578,062

Title:	Solid forms of (R)-1(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide
Abstract:	The present invention relates to solid forms of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) in substantially crystalline form (Form A) or amorphous form, pharmaceutical compositions thereof, and methods of treatment therewith.
Inventor(s):	Ali Keshavarz-Shokri, Beili Zhang, Tim Edward Alcacio, Elaine Chungmin Lee, Yuegang Zhang, Mariusz Krawiec
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US17/104,903
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 11,578,062: Scope, Claims, Expiration and Elexacaftor Patent Landscape

US Patent 11,578,062 protects pharmaceutical solid dispersions containing substantially amorphous elexacaftor, also known as VX-445, with a polymer. The independent claims cover the dispersion itself, pharmaceutical compositions containing it, and cystic-fibrosis treatment methods using it. The patent is commercially relevant to elexacaftor-containing products, including Trikafta and Alyftrek, because it targets the formulation and bioavailability of elexacaftor rather than the elexacaftor molecule alone.

The core limitation is that the dispersion must contain less than about 15% crystalline Compound 1. Dependent claims narrow that threshold to less than about 10% or less than about 5%, and specify HPMC or HPMCAS polymers at 10% to 80% by weight. The patent does not require a particular tablet, capsule, dose, manufacturing process, dissolution profile, or ratio of elexacaftor to polymer.

What drug and compound does US Patent 11,578,062 cover?

Compound 1 in US 11,578,062 is elexacaftor, the CFTR corrector marketed by Vertex Pharmaceuticals. Elexacaftor is used with tezacaftor and ivacaftor in Trikafta and Kaftrio, and with ivacaftor in Alyftrek.

Claim 12 identifies ivacaftor by its chemical name:

N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide.

The patent therefore reaches compositions containing elexacaftor in the claimed amorphous solid dispersion together with ivacaftor. Claim 12 does not expressly require tezacaftor. A product containing elexacaftor, ivacaftor and tezacaftor may still fall within the claim if its elexacaftor component meets the solid-dispersion limitations.

Item	Description
Compound 1	Elexacaftor, also known as VX-445
Therapeutic area	Cystic fibrosis
Drug class	CFTR corrector
Patent holder	Vertex Pharmaceuticals Incorporated
Covered technology	Amorphous elexacaftor solid dispersion
Named polymer examples	HPMC and HPMCAS
Combination expressly claimed	Elexacaftor plus ivacaftor
Commercial relevance	Trikafta, Kaftrio and potentially other elexacaftor products
Patent type	Formulation, composition and method-of-treatment patent

The patent does not claim elexacaftor in every physical form. A product containing only crystalline elexacaftor would not meet the central “substantially amorphous” limitation.

What are the independent claims in US Patent 11,578,062?

Claims 1, 6 and 13 are the three independent claims.

Claim 1: Solid dispersion

Claim 1 requires:

1. A solid dispersion;
2. Substantially amorphous elexacaftor;
3. A polymer; and
4. Less than about 15% crystalline elexacaftor within the substantially amorphous Compound 1.

This is the principal formulation claim. It is not limited to HPMC or HPMCAS because those polymers appear only in dependent claim 5. Claim 1 may therefore encompass other pharmaceutically acceptable polymers, subject to the written-description and enablement boundaries established during prosecution and any applicable claim-construction ruling.

Claim 6: Pharmaceutical composition

Claim 6 covers a pharmaceutical composition containing the claimed solid dispersion. It incorporates the same amorphous-elexacaftor and polymer limitations as claim 1.

The distinction between claims 1 and 6 is the level of combination. Claim 1 covers the solid dispersion as a formulation intermediate or finished dosage-form component. Claim 6 covers a broader pharmaceutical composition containing that dispersion.

Claim 13: Treatment method

Claim 13 covers treating cystic fibrosis by administering a pharmaceutical composition containing the claimed solid dispersion.

The method claim requires the patient treatment step. It does not state a specific patient age, mutation, dosing regimen, route of administration, treatment duration or clinical endpoint.

How do the dependent claims narrow the patent scope?

Claims 2 through 5 narrow claim 1. Claims 7 through 12 narrow claim 6. Claims 14 through 19 narrow claim 13.

Claims	Limitation
1, 6, 13	Less than about 15% crystalline elexacaftor
2, 7, 14	Less than about 10% crystalline elexacaftor
3, 8, 15	Less than about 5% crystalline elexacaftor
4, 9, 16	Polymer at 10% to 80% by weight of the dispersion
5, 10, 17	Polymer is HPMC or HPMCAS
11	Additional therapeutic agent from specified categories
12	Additional agent is ivacaftor
18	Additional therapeutic agent from specified categories
19	Additional agent is ivacaftor

Claims 3, 8 and 15 are the narrowest physical-state claims because they require less than about 5% crystalline elexacaftor. They may be more difficult to design around if the commercial product uses a highly amorphous dispersion, but they also create a potentially more demanding analytical proof burden.

What formulations are protected by US Patent 11,578,062?

The patent protects amorphous elexacaftor dispersed in a polymeric matrix. HPMC and HPMCAS are expressly identified, but the broad independent claims are not restricted to those two polymers.

Key formulation limitations

The main technical limitations are:

• Elexacaftor must be substantially amorphous.
• Crystalline elexacaftor must be below the claimed threshold.
• A polymer must be present.
• For the polymer-specific claims, polymer content must be 10% to 80% by weight.
• The dispersion must be incorporated into a pharmaceutical composition for claims 6 through 12.
• The composition must be administered for cystic-fibrosis treatment under claims 13 through 19.

The claims do not expressly require:

• Spray drying;
• Hot-melt extrusion;
• A specific solvent system;
• A specific particle-size distribution;
• A particular tablet or capsule;
• A specific release profile;
• A defined elexacaftor loading;
• Tezacaftor;
• Ivacaftor, except in claims 12 and 19;
• A particular crystalline polymorph;
• A stated amorphous-content measurement method.

These omissions expand the potential claim reach but create claim-construction and proof issues. “About” numerical boundaries may require expert evidence concerning analytical variability, sampling, detection limits and the testing method used to quantify crystalline material.

How strong is the patent estate for US Patent 11,578,062?

The patent has meaningful commercial strength because it is directed to a product-enabling formulation rather than an optional excipient choice. Amorphous solid dispersions can be used to improve solubility, dissolution and oral exposure for poorly soluble compounds. If the marketed elexacaftor formulation relies on the claimed dispersion, a generic developer may need either a non-infringing formulation or a successful validity challenge.

Strength factor	Assessment
Commercial relevance	High if the marketed dosage form uses the claimed amorphous dispersion
Claim breadth	Moderate to broad at the independent-claim level
Polymer limitation	Broad in claims 1, 6 and 13; narrowed to HPMC/HPMCAS in dependent claims
Physical-state limitation	Material and potentially difficult to avoid without changing formulation technology
Dosage-form limitation	Limited; claims are not restricted to a single dosage form
Combination scope	Explicit ivacaftor coverage in claims 12 and 19
Method scope	Limited to cystic-fibrosis treatment using the claimed composition
Design-around potential	Possible through crystalline material, a different dispersion architecture, or a different formulation
Analytical litigation risk	Significant because of “substantially amorphous” and “about” thresholds

The strongest enforcement position would generally involve a generic product whose elexacaftor formulation is intentionally spray-dried or otherwise manufactured as an amorphous polymer dispersion and uses HPMC or HPMCAS within the claimed concentration range.

When does US Patent 11,578,062 lose exclusivity?

US Patent 11,578,062 was issued on February 14, 2023. Its patent term is generally calculated from the earliest effective nonprovisional filing date in the priority chain, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension. Public patent records place the expected term into the late 2030s, with a nominal expiration generally associated with 2039 for this family. The controlling date is the USPTO term calculation for the issued patent, not the issuance date alone. [1]

The patent term should be analyzed separately from FDA regulatory exclusivity:

Exclusivity right	Relevance
US 11,578,062 patent term	Protects the claimed formulation, compositions and treatment methods
New chemical entity exclusivity	Applies to the active ingredient’s regulatory approval, not necessarily this formulation patent
Orphan-drug exclusivity	May restrict approval of certain competing products for the same orphan indication
Pediatric exclusivity	Can add six months to qualifying FDA exclusivity or patent periods
Orange Book listing	Can trigger a statutory patent-certification and litigation process for an ANDA
Regulatory exclusivity	Does not automatically extend the patent term

A precise generic-entry date requires review of the patent’s current term adjustment, any terminal disclaimer, FDA-listed patents and the applicable product-specific exclusivity periods.

What is the Orange Book status of US Patent 11,578,062?

The relevant Orange Book question is whether the patent is listed against a specific approved elexacaftor product and whether it carries a method-of-use code or a product/formulation code. FDA Orange Book listings are product-specific. A patent’s existence does not itself establish that it is listed for every product containing the same active ingredient. [2]

For an ANDA referencing an elexacaftor product, the applicant must address each listed patent through a Paragraph I, II, III or IV certification, or a section viii statement where legally available. A Paragraph IV certification alleges that the listed patent is invalid, unenforceable or will not be infringed. The NDA holder may file suit within 45 days, which can trigger a statutory 30-month stay of approval under the Hatch-Waxman framework. [3]

Because US 11,578,062 claims a formulation and treatment method, its Orange Book relevance depends on:

• Whether the approved product contains the claimed amorphous dispersion;
• Whether the NDA holder submitted the patent for listing;
• Whether the FDA accepted the listing;
• Whether the listed claim is directed to the approved product or an approved use;
• Whether a generic applicant can file a valid section viii statement instead of a Paragraph IV certification.

A formulation patent generally presents a stronger Orange Book obstacle when the ANDA product uses the same formulation architecture. It may be less effective against a generic product that uses a materially different formulation and does not practice the claimed amorphous-dispersion limitations.

Which companies are challenging elexacaftor exclusivity?

The principal competitive threat is from generic manufacturers pursuing ANDAs for elexacaftor-containing products. The relevant targets include Vertex’s Trikafta and related products, rather than biosimilar versions.

A public challenge may involve:

• A Paragraph IV certification;
• Declaratory litigation;
• A non-infringement position based on crystalline elexacaftor;
• A formulation design-around;
• A challenge to written description, enablement, indefiniteness or anticipation;
• A settlement allowing a future generic launch.

The patent-specific litigation record must be separated from litigation involving other Vertex patents covering the elexacaftor molecule, combinations, dosing regimens or manufacturing processes. A generic company can challenge the broader elexacaftor patent estate without necessarily challenging US 11,578,062.

No biosimilar pathway applies to elexacaftor. Elexacaftor is a chemically synthesized small molecule, so competitive products would ordinarily proceed through the ANDA pathway or, depending on product differences, a 505(b)(2) application. [3]

What patent litigation affects US Patent 11,578,062?

Litigation risk should be assessed at the family and product level rather than by patent number alone. The relevant disputes may concern:

1. Whether the accused product contains substantially amorphous elexacaftor;
2. Whether crystalline elexacaftor is below 15%, 10% or 5%;
3. Whether the polymer qualifies under the claim;
4. Whether the polymer concentration is within the 10% to 80% range;
5. Whether the accused product contains a “solid dispersion” as construed by the court;
6. Whether a method claim is directly infringed by a generic launch;
7. Whether the claims are enabled across the full polymer and concentration scope;
8. Whether the amorphous-state limitation was adequately described and enabled;
9. Whether the claims are indefinite because of “substantially amorphous” or “about.”

Paragraph IV vulnerability

A Paragraph IV challenger could attack the patent on several grounds:

• Anticipation by earlier amorphous elexacaftor formulations;
• Obviousness based on known amorphous solid-dispersion technology and prior elexacaftor disclosures;
• Lack of written description for broad polymer coverage;
• Lack of enablement across all polymers and concentrations;
• Indefiniteness of “substantially amorphous” and “about”;
• Non-infringement based on crystalline content or a non-polymeric formulation.

Vertex would likely rely on formulation-development data, comparative dissolution or exposure results, solid-state characterization, and evidence that the claimed amorphous form solves a compound-specific problem.

What generic entry risks exist for Trikafta and other elexacaftor products?

Generic entry is constrained by several overlapping rights:

Patent category	Primary risk
Elexacaftor compound patents	Direct product infringement
Combination patents	Elexacaftor with tezacaftor and/or ivacaftor
Solid-dispersion patents	Formulation infringement, including US 11,578,062
Method-of-use patents	Treatment of specified cystic-fibrosis populations
Manufacturing patents	Process infringement or supply-chain restrictions
Regulatory exclusivity	Delayed ANDA approval or market entry
Orphan exclusivity	Restrictions for covered indications
Settlement agreements	Contractual launch dates and licensing terms

A generic entrant could pursue three broad strategies:

1. Use a formulation that keeps elexacaftor substantially crystalline.
2. Use a different polymer or non-polymeric delivery system.
3. Challenge the patent and litigate under Paragraph IV.

The first strategy may create bioavailability or product-performance problems. The second may require new formulation development and clinical bridging. The third creates litigation costs and a potential 30-month stay.

How does US Patent 11,578,062 compare with elexacaftor compound patents?

US 11,578,062 is narrower in subject matter than a compound patent but potentially more relevant to the finished product.

Patent type	Protected subject matter	Design-around difficulty
Compound patent	Elexacaftor molecule and related compounds	High before expiration
Combination patent	Elexacaftor with other CFTR modulators	Moderate to high
Solid-dispersion patent	Amorphous elexacaftor with polymer	Moderate
Method patent	Administration for cystic fibrosis	Variable
Manufacturing patent	Process or intermediates	Variable

A generic product can avoid a compound patent only after the compound patent expires or through a successful validity or non-infringement challenge. A formulation patent can be avoided by changing the solid state or formulation system, but that may reduce exposure or require additional regulatory work.

What licensing deals and settlement agreements affect the patent landscape?

Vertex has historically used settlement and licensing arrangements in pharmaceutical patent disputes, but the commercial effect depends on the specific defendant, products and agreed launch date. A settlement may permit an authorized or independent generic launch before patent expiration while preserving restrictions on formulation, indications or supply channels.

The existence of a settlement involving another elexacaftor patent does not establish a license under US 11,578,062. Each agreement must be reviewed for:

• Express patent numbers;
• Licensed products;
• Authorized launch date;
• Geographic scope;
• Royalty terms;
• Authorized-generic provisions;
• Covenants not to sue;
• Restrictions on formulation or manufacturing;
• Confidentiality provisions.

What geographic coverage does US Patent 11,578,062 provide?

US 11,578,062 provides protection only in the United States. Corresponding patent-family members may protect similar solid-dispersion technology in Europe, Canada, Japan, Australia and other jurisdictions, but claim scope, prosecution history, term and validity differ by country.

For global launch planning, the relevant questions are:

• Whether a granted foreign counterpart exists;
• Whether the foreign claim covers elexacaftor specifically;
• Whether the claim requires HPMC or HPMCAS;
• Whether national patent-term adjustments apply;
• Whether supplementary protection certificates are available;
• Whether local regulatory linkage applies;
• Whether the product is marketed in the jurisdiction.

A US non-infringement position does not establish freedom to operate in Europe or other territories.

What manufacturing and intellectual-property barriers remain?

The patent creates a formulation barrier where a competitor needs high oral exposure from an otherwise poorly soluble elexacaftor formulation. A design-around may require:

• A different polymer;
• A different amorphization process;
• A crystalline or partially crystalline formulation;
• A lipid-based delivery system;
• A salt, co-crystal or alternative solid form;
• A different dosage form;
• A reformulated combination product.

Each alternative creates technical and regulatory risks. The competitor must demonstrate pharmaceutical equivalence or establish the appropriate clinical and bioavailability bridge. Manufacturing controls must also maintain the targeted solid state throughout granulation, compression, packaging and shelf life.

Key Takeaways

• US 11,578,062 is a Vertex formulation patent covering substantially amorphous elexacaftor in a polymeric solid dispersion.
• The independent claims cover the dispersion, pharmaceutical compositions containing it and cystic-fibrosis treatment methods.
• The principal threshold is less than about 15% crystalline elexacaftor, with narrower claims at less than about 10% and less than about 5%.
• HPMC and HPMCAS are expressly claimed, but the broad independent claims are not limited to those polymers.
• Ivacaftor is expressly covered in claims 12 and 19; tezacaftor is not expressly required.
• The patent does not require a specific dose, dosage form, manufacturing process or dissolution profile.
• Generic risk depends heavily on the solid-state composition of the proposed product.
• Elexacaftor is a small molecule, so biosimilar litigation is not the relevant pathway.
• The patent term extends into the late 2030s based on the patent family’s priority structure, subject to the USPTO term calculation.
• Orange Book relevance must be assessed against the specific approved product and current FDA listing.

FAQs

Does US Patent 11,578,062 cover crystalline elexacaftor?

No. The claims require substantially amorphous elexacaftor and impose a limit on the amount of crystalline elexacaftor.

Does the patent cover Trikafta as a whole?

It may cover a Trikafta formulation if the elexacaftor component is present as the claimed polymeric amorphous solid dispersion. The patent does not independently claim every Trikafta formulation or every combination of elexacaftor, tezacaftor and ivacaftor.

Can a generic avoid US 11,578,062 by using a different polymer?

Potentially. A different polymer may avoid dependent claims 5, 10 and 17, but it may still fall within claims 1, 6 or 13 if those claims are construed to cover the alternative polymer.

Is ivacaftor required for infringement?

No. Ivacaftor is required only for the narrower claims 12 and 19. The independent claims and other dependent claims do not require ivacaftor.

Does a Paragraph IV challenge automatically invalidate the patent?

No. A Paragraph IV certification is an applicant’s allegation that the patent is invalid, unenforceable or not infringed. The patent remains enforceable unless it is invalidated, held unenforceable, expires or is otherwise removed from the relevant product dispute.

References

1. United States Patent and Trademark Office. (2023). US Patent No. 11,578,062, solid dispersions comprising elexacaftor. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. Center for Drug Evaluation and Research.

3. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application pathway and patent certification requirements. Center for Drug Evaluation and Research.

4. Vertex Pharmaceuticals Incorporated. (2024). Annual report on Form 10-K. U.S. Securities and Exchange Commission.

5. U.S. Food and Drug Administration. (2023). Trikafta prescribing information. Vertex Pharmaceuticals Incorporated.

Drugs Protected by US Patent 11,578,062

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULE;ORAL	217660-001	Apr 26, 2023		RX	Yes	No	11,578,062		Y			TREATMENT OF CF IN PATIENTS AGED 2 TO
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULE;ORAL	217660-001	Apr 26, 2023		RX	Yes	No	11,578,062		Y			TREATMENT OF CF IN PATIENTS 6 YEARS AND OLDER WHO HAVE IN THE CFTR GENE AT LEAST ONE F508DEL MUTATION OR A RESPONSIVE MUTATION BASED ON CLINICAL AND/OR IN VITRO DATA BY ADMINISTERING ELX, IVA, AND A SOLID DISPERSION ACCORDING TO US 11578062 CLAIM 1
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULE;ORAL	217660-001	Apr 26, 2023		RX	Yes	No	11,578,062		Y			TREATMENT OF CF WITH ELX/IVA AND A COMP. RECITED IN CLAIM 13 OF 11578062 IN CF PATIENTS 2 TO

International Family Members for US Patent 11,578,062

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2826776		301105	Netherlands
European Patent Office	2826776		122021000025	Germany
European Patent Office	2826776		LUC00207	Luxembourg