Details for Patent: 8,410,274

Which drugs does patent 8,410,274 protect, and when does it expire?

Patent 8,410,274 protects TRIKAFTA (COPACKAGED), ALYFTREK, SYMDEKO (COPACKAGED), KALYDECO, and ORKAMBI, and is included in eight NDAs.

Protection for KALYDECO has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has thirty-four patent family members in nineteen countries.

Summary for Patent: 8,410,274

Title:	Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
Abstract:	The present invention relates to solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.
Inventor(s):	Patricia Hurter, William Rowe, Christopher Ryan Young, Adriana Costache, Patrick R. Connelly, Mariusz Krawiec, Yuchuan Gong, Yushi Feng, Martin Trudeau
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US13/358,778
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,410,274
Patent Claim Types: see list of patent claims	Composition; Compound;

United States Patent 8,410,274: Solid-Dispersion Patent Scope, Claim Analysis, and Generic-Entry Risk

US 8,410,274 protects pharmaceutical solid dispersions containing amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide. The patent is directed primarily to formulation technology rather than the underlying chemical entity. Its strongest protection covers dispersions using HPMCAS, particularly when combined with sodium lauryl sulfate and produced by spray drying.

The most commercially important claims are claims 1, 4, 9, 12, 20, 21, and 22. A product can avoid the narrowest claims by using a crystalline form, a different polymer, a different surfactant, or a manufacturing process other than spray drying. It may still infringe broader claims 1, 2, 3, 13, 14, 18, or 19 if it contains the claimed amorphous compound in a solid dispersion.

What does US Patent 8,410,274 protect?

The patent protects a formulation containing the specified quinolinone carboxamide in amorphous form, dispersed within a solid carrier system. The broadest technical concept is:

1. The active ingredient must be the identified quinolinone carboxamide.
2. The active ingredient must be amorphous where the claim expressly requires that characteristic.
3. The active ingredient must be present as a solid dispersion.
4. The dispersion may contain a polymer, surfactant, or inert pharmaceutically acceptable substance.
5. Certain dependent claims narrow the formulation to HPMC, HPMCAS, sodium lauryl sulfate, defined concentration ranges, or spray drying.

The patent does not, based on the supplied claims, claim every pharmaceutical use of the compound, every dosage form, or the compound in all physical forms.

Core claim architecture

Claim group	Subject matter	Relative breadth
1	Solid dispersion containing amorphous active ingredient	Broad
2	Claim 1 plus surfactant, polymer, or inert substance	Broad but narrowed
3	Claim 1 plus polymer	Broad formulation claim
4	Claim 3 with HPMCAS	Narrower
5-6	Polymer concentration ranges	Narrower
7	Active-ingredient concentration range	Narrower
8-11	Surfactant, including sodium lauryl sulfate and 0.5% concentration	Narrow
12	Spray-dried dispersion	Process-linked product limitation
13	Pharmaceutical composition containing amorphous active as solid dispersion	Broad composition claim
14-17	Composition with HPMC, HPMCAS, or other water-soluble polymers	Intermediate
18-20	Composition with polymer, particularly HPMCAS	Intermediate to narrow
21	Dispersion with active ingredient, HPMCAS, and sodium lauryl sulfate	Narrow but commercially important
22	Pharmaceutical composition containing claim 21 dispersion	Narrow

How should claim 1 be construed?

Claim 1 requires a “solid dispersion comprising amorphous” active ingredient. Each limitation matters.

“Solid dispersion”

A solid dispersion generally means a solid product in which one or more components are dispersed in a solid carrier or matrix. The claim is broader than a tablet claim and can cover:

• Spray-dried powders
• Granules
• Intermediate formulation blends
• Capsules containing the dispersion
• Tablets manufactured from the dispersion
• Other solid dosage forms incorporating the dispersion

The claim does not expressly require a particular dosage form, particle size, dissolution profile, polymer, or manufacturing technique.

A simple physical mixture of crystalline drug and excipient should not meet the solid-dispersion limitation merely because it is a solid pharmaceutical product. The relevant distinction is whether the drug is dispersed in the solid carrier system and whether the claimed amorphous state is present.

“Amorphous” active ingredient

The amorphous limitation is a central infringement and validity issue. An accused product must be assessed using solid-state characterization methods such as:

• Powder X-ray diffraction
• Differential scanning calorimetry
• Thermogravimetric analysis
• Solid-state nuclear magnetic resonance
• Infrared or Raman spectroscopy
• Microscopy and dissolution testing

A formulation can contain both amorphous and crystalline material. The infringement analysis would depend on claim construction, the degree of amorphous content required, and whether the relevant product batch contains the claimed amorphous form.

A product that contains only the crystalline active ingredient has a credible non-infringement position against claims expressly requiring amorphous active ingredient. That position would not automatically address claims directed to a solid dispersion where amorphous character is implied or not expressly repeated.

Which claims cover HPMCAS formulations?

Claims 4, 20, and 21 provide the clearest HPMCAS coverage.

Claim 4

Claim 4 requires:

• The solid dispersion of claim 3
• A polymer
• HPMCAS as the polymer

Because claim 4 depends on claim 3, the formulation must also satisfy claim 1. The active ingredient must therefore be present as an amorphous solid dispersion, and HPMCAS must be the polymer component.

Claim 20

Claim 20 covers a pharmaceutical composition comprising the amorphous active ingredient as a solid dispersion and HPMCAS. It is structurally similar to claim 4 but is framed as a pharmaceutical composition rather than merely a solid dispersion.

Claim 21

Claim 21 is the most formulation-specific claim:

• The quinolinone carboxamide
• HPMCAS
• Sodium lauryl sulfate

The claim does not expressly state a concentration for HPMCAS or sodium lauryl sulfate. It also does not expressly repeat the word “amorphous,” although the claim requires a “solid dispersion.” The scope of claim 21 will depend heavily on how “solid dispersion” is construed and whether amorphous character is treated as an inherent feature of the claimed dispersion.

What formulations are protected by the polymer claims?

Claims 3, 4, 5, 6, 14, 15, 16, 17, 18, 19, and 20 protect polymer-containing formulations.

Polymer concentration

Claim 5 covers polymer levels from about 10% to about 80% by weight. Claim 6 narrows that range to less than about 70% by weight.

The terms “about” and “less than about” create potential boundary disputes. A formulation containing 70% polymer may fall outside claim 6 while remaining within claim 5, depending on the applicable construction of “about.” A product at 10%, 80%, or 70% should be analyzed against the specification, prosecution history, measurement method, and batch tolerances.

Active-ingredient concentration

Claim 7 covers active-ingredient levels from about 10% to about 80% by weight. A product can fall outside claim 7 while remaining within claim 1 if it uses a concentration below or above the stated range.

Claims 1 and 13 do not impose an express active-ingredient concentration limitation. They therefore present greater formulation breadth.

Water-soluble and partially water-soluble polymers

Claims 16, 17, and 19 cover at least one water-soluble or partially water-soluble polymer. These claims may reach polymers other than HPMC and HPMCAS if the polymer satisfies the solubility limitation.

Potentially relevant polymer classes include:

• HPMC
• HPMCAS
• Hydroxypropyl cellulose
• Polyvinylpyrrolidone
• Copovidone
• Polyethylene oxide
• Other pharmaceutically acceptable water-soluble or partially water-soluble polymers

The precise scope depends on the patent specification and prosecution history. The claims do not appear limited to a single polymer grade, substitution level, viscosity, or particle size unless those limitations appear elsewhere in the patent.

What protection does the surfactant claim provide?

Claims 8 through 11 address surfactant-containing dispersions.

Claim 8 broadly requires a surfactant. Claim 9 narrows the surfactant to sodium lauryl sulfate. Claim 10 requires a surfactant concentration of about 0.1% to about 5%. Claim 11 narrows the concentration to 0.5%.

A formulation using sodium lauryl sulfate at 0.5% is the clearest target of claims 9 through 11, assuming the formulation also satisfies the incorporated limitations of claim 8 and claim 1.

A formulation using another surfactant may avoid claims 9 through 11 but remain exposed under claim 8. A product without any surfactant may avoid claims 8 through 11 while remaining exposed to the polymer claims.

Does spray drying create separate infringement risk?

Yes. Claim 12 expressly covers a solid dispersion “obtained by spray drying.” A spray-dried formulation can face an additional infringement theory under claim 12 if it also meets the incorporated limitations of claim 1.

Spray drying is commercially significant because it is a common method for converting poorly soluble drug substances into amorphous dispersions. The process can produce:

• Amorphous drug-polymer particles
• Improved dissolution
• Improved apparent solubility
• Enhanced bioavailability
• More uniform drug distribution

A manufacturer using hot-melt extrusion, solvent evaporation, freeze drying, fluid-bed processing, or another technique may avoid claim 12. That alternative does not necessarily avoid claims 1, 3, 13, 18, 20, or 21, which are not expressly limited to spray drying.

How strong is the patent estate for the claimed formulation?

The estate appears strongest against a formulation that reproduces the patent’s central technical solution: amorphous active ingredient dispersed in HPMCAS, with sodium lauryl sulfate and potentially spray drying.

Strongest infringement positions

Accused feature	Relevant claims
Amorphous active in solid dispersion	1, 13
Amorphous active plus polymer	3, 14, 18
HPMCAS dispersion	4, 15, 20
Water-soluble or partially water-soluble polymer	16, 17, 19
Sodium lauryl sulfate	9, 21
Surfactant at 0.1%-5%	10
Surfactant at approximately 0.5%	11
Spray drying	12
HPMCAS plus sodium lauryl sulfate	21, 22

Weaknesses and design-around opportunities

The supplied claims leave several potential design-around paths:

1. Use crystalline rather than amorphous active ingredient.
2. Use a nonpolymeric carrier or a different inert excipient.
3. Use a polymer outside the water-soluble or partially water-soluble category.
4. Replace HPMCAS with another polymer.
5. Omit sodium lauryl sulfate.
6. Use a surfactant concentration outside the claimed range.
7. Use a manufacturing method other than spray drying.
8. Formulate the active ingredient in a liquid, lipid, crystalline, or nanoparticulate system rather than a solid dispersion.

The first design-around is technically difficult if the drug has poor solubility and the commercial product depends on amorphous dispersion technology. The legal risk is lower if the alternative formulation is demonstrably crystalline and does not contain an amorphous fraction that satisfies the claims.

What is the likely patent expiration timing?

A US utility patent generally has a term of 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory modifications. The grant date of US 8,410,274 does not determine expiration. The patent was granted on April 2, 2013, but the relevant term calculation must be based on the patent’s priority and application history.[1][2]

The exact expiration date should be taken from the USPTO Patent Center file history and the patent’s term-adjustment data. A continuation, divisional, or international application can have the same effective term as the parent family application. Patent-term adjustment may extend the nominal 20-year term, while a terminal disclaimer can shorten it.

Exclusivity timeline

Event	Relevance
Earliest effective nonprovisional filing	Starts the 20-year patent term calculation
US application filing	Establishes prosecution record
Patent grant	Creates enforceable issued claims
Patent-term adjustment	May extend expiration
FDA approval of a drug product	May create separate regulatory exclusivity
Orange Book listing	Determines listed patent exposure for an ANDA
Paragraph IV certification	Creates potential patent litigation
Patent expiration	Removes ordinary infringement liability for unexpired claims

No conclusion about FDA regulatory exclusivity can be drawn solely from the patent claims. Patent protection and FDA exclusivity are separate rights.

What is the Orange Book status of the claimed compound and formulation?

The supplied claims do not identify the active ingredient by a nonproprietary drug name, development code, NDA number, or approved product. The chemical name alone is insufficient to establish an Orange Book listing or identify an approved product with certainty.

Orange Book relevance depends on whether:

• The compound has an approved New Drug Application.
• The patented formulation is approved for commercial use.
• The patent owner or NDA holder submitted the patent for listing.
• FDA accepted the listing under its patent-listing standards.
• The patent claims a drug substance, drug product, or method of use associated with the approved product.[3]

A formulation patent may be listed if it claims an approved drug product or an approved formulation. A patent directed only to an unapproved formulation, development-stage composition, or formulation not used in the approved product may not create Orange Book-listed ANDA exposure.

Are Paragraph IV challenges likely?

A Paragraph IV certification is relevant only if the patent is listed in the Orange Book against an approved reference listed drug. If listed, an ANDA applicant could assert that:

• The patent is invalid.
• The patent is unenforceable.
• The proposed generic does not infringe.

Potential Paragraph IV positions

A generic applicant could develop a non-infringing formulation based on:

• A crystalline drug form
• A different polymer
• No polymer
• A non-HPMCAS polymer
• No sodium lauryl sulfate
• A different surfactant
• A non-spray-drying process
• A formulation that does not contain the claimed amorphous solid dispersion

An invalidity challenge could focus on:

• Anticipation by an earlier amorphous dispersion publication
• Obviousness based on known solid-dispersion technology
• Written-description support for the full breadth of polymer, surfactant, and concentration ranges
• Enablement across the claimed formulation space
• Indefiniteness involving “about,” “solid dispersion,” or “amorphous”
• Lack of priority support for the issued claims

The commercial strength of a Paragraph IV challenge would depend on prior-art disclosures directed to this specific quinolinone compound, not merely to generic amorphous dispersions.

What patent litigation affects US 8,410,274?

The claim set alone does not establish a litigation history, settlement, consent judgment, or covenant not to sue. Litigation research should distinguish among:

• District-court infringement actions
• ANDA litigation under the Hatch-Waxman Act
• Inter partes review proceedings
• Post-grant review
• Patent-term disputes
• FDA patent-listing disputes
• Settlement agreements involving generic entry

A Paragraph IV notice, if served, would ordinarily identify the challenged claims and trigger the statutory framework under 21 U.S.C. §355(j)(5)(B)(iii). A timely infringement action can create a 30-month stay of ANDA approval, subject to statutory exceptions.[4]

There is no basis in the supplied claim text to infer that the patent has been litigated or settled.

What companies are challenging the patent?

The claim information does not identify an ANDA filer, biosimilar applicant, licensee, or litigation defendant. The patent covers a small-molecule formulation, not a biologic. Biosimilar litigation under the Biologics Price Competition and Innovation Act is therefore not the expected pathway.

The relevant challengers, if an approved product exists, would be generic-drug manufacturers filing ANDAs. Potential participants would include companies with capabilities in:

• Amorphous solid-dispersion development
• HPMCAS formulation
• Spray drying
• Poorly soluble small-molecule products
• Paragraph IV litigation

A company can challenge the patent without copying the patented formulation by pursuing a different physical form or formulation route.

How does this patent compare with a drug-substance patent?

Issue	US 8,410,274	Drug-substance patent
Protected subject matter	Amorphous solid dispersion and pharmaceutical composition	Chemical entity or active ingredient
Typical breadth	Formulation-specific	Often broader across dosage forms
Design-around potential	Relatively substantial	Usually more limited before expiry
Orange Book role	Depends on approved formulation	Often directly tied to approved active ingredient
Generic strategy	Alternative formulation or physical form	Challenge compound claims or delay launch
Manufacturing relevance	High	Depends on process claims
Biosimilar relevance	None for small molecule	None for small molecule

A formulation patent can remain commercially relevant after a compound patent expires, but only if the approved product depends on the claimed formulation and the patent is valid, enforceable, and properly listed.

What manufacturing and intellectual-property barriers exist?

The technical barrier is the reproducible manufacture of a stable amorphous dispersion. Amorphous systems can recrystallize during storage, processing, or exposure to humidity. A generic developer must control:

• Polymer grade and substitution profile
• Drug-to-polymer ratio
• Residual solvent
• Spray-dryer inlet and outlet temperatures
• Feed concentration
• Atomization conditions
• Particle morphology
• Moisture content
• Physical stability
• Dissolution after storage
• Scale-up performance

HPMCAS can provide pH-dependent release and precipitation inhibition. Sodium lauryl sulfate can improve wetting and dispersion but may affect stability, tolerability, and downstream tableting. These technical dependencies may increase development cost even where a legal design-around is available.

The patent does not, in the supplied claims, separately claim a specific spray-dryer configuration, particle-size distribution, dissolution threshold, storage condition, or release profile.

What revenue exposure could the patent create?

Revenue exposure cannot be quantified from the patent number alone because the patent record supplied does not identify:

• The approved product
• The NDA holder
• Annual sales
• Market share
• Patent-listing status
• Generic filing activity
• Settlement terms
• Product dependence on the claimed dispersion

Commercial exposure would be highest if the patent protects the only approved formulation for a high-value product and is listed in the Orange Book. Exposure would be lower if the marketed product uses a different formulation, if no product has been approved, or if an effective non-infringing formulation is available.

Key Takeaways

• US 8,410,274 is a formulation patent, not a broad chemical-entity patent.
• Its central protection is an amorphous solid dispersion of the specified quinolinone carboxamide.
• HPMCAS claims are concentrated in claims 4, 15, and 20.
• The HPMCAS-plus-sodium-lauryl-sulfate combination is specifically covered by claim 21.
• Spray-dried formulations face additional exposure under claim 12.
• A crystalline formulation, non-HPMCAS polymer, alternative surfactant, or non-spray-drying process may provide design-around opportunities.
• Claims 1, 3, 13, 18, and 19 create broader residual risk beyond the narrow HPMCAS and surfactant claims.
• Orange Book, Paragraph IV, litigation, settlement, and revenue conclusions require linkage to an approved product and its regulatory record.
• The patent term must be calculated from the effective filing history, with patent-term adjustment and any terminal disclaimer taken into account.
• The principal technical barrier is maintaining a stable amorphous dispersion during scale-up and storage.

FAQs

Does US 8,410,274 cover tablets containing the solid dispersion?

Potentially. Claims 13 and 22 cover pharmaceutical compositions containing the claimed dispersion. A tablet incorporating the required dispersion may fall within those claims even though the claims do not expressly require a tablet.

Can a generic avoid the patent by replacing HPMCAS with HPMC?

Possibly. Replacing HPMCAS may avoid claims specifically limited to HPMCAS, including claims 4 and 20. The generic could remain exposed to broader polymer claims if the formulation still contains the claimed amorphous active ingredient in a solid dispersion.

Does a product using sodium lauryl sulfate automatically infringe claim 21?

No. Claim 21 requires the claimed active ingredient, HPMCAS, and sodium lauryl sulfate in a solid dispersion. Sodium lauryl sulfate alone is insufficient.

Is a spray-dried crystalline formulation outside claim 12?

Potentially, but the answer depends on whether the final product is a solid dispersion containing amorphous active ingredient. Spray drying alone does not establish infringement. The product must satisfy the incorporated limitations of claim 1.

Can the patent block a generic after the compound patent expires?

Yes, if the formulation patent remains unexpired, valid, enforceable, and applicable to the generic product. Its practical blocking effect depends on Orange Book listing, the approved product, the generic formulation, and available non-infringing alternatives.

References

1. United States Patent and Trademark Office. (n.d.). Patent term adjustment. https://www.uspto.gov/patents/uspto-patent-term-calculator
2. United States Patent and Trademark Office. (2013). United States Patent No. 8,410,274.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
4. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
5. United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/

Drugs Protected by US Patent 8,410,274

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	8,410,274		Y
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	GRANULE;ORAL	217660-002	Apr 26, 2023		RX	Yes	Yes	8,410,274		Y
Vertex Pharms Inc	ALYFTREK	deutivacaftor; tezacaftor; vanzacaftor calcium	TABLET;ORAL	218730-001	Dec 20, 2024		RX	Yes	No	8,410,274		Y

International Family Members for US Patent 8,410,274

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006332726
Brazil	PI0620960
Canada	2635581