US Patent 8,067,472: Vorinostat Dosing Claims, Scope, Expiration, and Generic Risk

US Patent 8,067,472 protects specific oral dosing regimens of suberoylanilide hydroxamic acid, also known as SAHA or vorinostat, for non-Hodgkin's lymphoma and Hodgkin's lymphoma. Claim 1 covers 400 mg administered once daily for non-Hodgkin's lymphoma. Claim 3 covers 200 mg administered twice daily for Hodgkin's lymphoma. Claims 2 and 4 add no material limitation beyond the parent claims because they expressly identify SAHA, which is already included in claims 1 and 3.

The patent issued November 29, 2011, and its ordinary 20-year patent term ran from the relevant nonprovisional filing date to approximately March 11, 2025. The patent is therefore no longer an active US exclusion right based on its ordinary term. The underlying compound, formulation, regulatory, and other method patents must be analyzed separately because expiration of US 8,067,472 did not eliminate every potential barrier to vorinostat entry.

What does US Patent 8,067,472 protect?

The patent protects treatment methods defined by both disease and dose. It does not broadly claim vorinostat as a chemical compound, every use of vorinostat, or every dosage form.

Claim	Disease	Route	Dose	Active ingredient scope	Practical scope
1	Non-Hodgkin's lymphoma	Oral	400 mg once daily	SAHA, or pharmaceutically acceptable salt or hydrate	Direct treatment method using a once-daily 400 mg regimen
2	Non-Hodgkin's lymphoma	Oral	400 mg once daily	SAHA specifically	Dependent claim confirming the free compound
3	Hodgkin's lymphoma	Oral	200 mg twice daily	SAHA, or pharmaceutically acceptable salt or hydrate	Direct treatment method using a divided 400 mg daily regimen
4	Hodgkin's lymphoma	Oral	200 mg twice daily	SAHA specifically	Dependent claim confirming the free compound

What is the active ingredient covered by the patent?

SAHA is vorinostat, the active pharmaceutical ingredient in Zolinza. Vorinostat is a histone deacetylase inhibitor. The claim language encompasses the named compound and, in the independent claims, a pharmaceutically acceptable salt or hydrate.

The claims do not expressly require:

a particular crystalline form;
a particular capsule shell;
a specific excipient;
a particular patient age;
relapsed or refractory disease;
a particular chemotherapy combination;
a biomarker;
a treatment duration;
a response threshold; or
a specific manufacturing process.

The patent therefore operates as a regimen patent. Its limiting elements are the lymphoma diagnosis, oral administration, and specified dose schedule.

How should the claims be construed?

What are the mandatory elements of claim 1?

A claim 1 infringement theory would generally require proof that:

A patient has non-Hodgkin's lymphoma.
The accused product contains SAHA, or a covered salt or hydrate.
The product is administered orally.
The patient receives a single daily dose of 400 mg.

The phrase "a single dose of 400 mg daily" is important. It distinguishes a once-daily regimen from divided dosing. A patient receiving 200 mg twice daily would not literally satisfy the once-daily limitation in claim 1, although that regimen is separately addressed in claim 3 for Hodgkin's lymphoma.

What are the mandatory elements of claim 3?

Claim 3 requires:

A patient with Hodgkin's lymphoma.
Oral administration.
SAHA, or a covered salt or hydrate.
200 mg administered twice daily.

The total daily amount is 400 mg, but the claim is directed to dose frequency and unit dose. A 400 mg once-daily regimen is not the same claimed schedule as 200 mg twice daily.

Do claims 2 and 4 materially expand protection?

No. Claims 2 and 4 are narrower in form but add little practical scope. The independent claims already expressly identify SAHA as an encompassed substance. The dependent claims may have provided fallback positions during prosecution, but they do not create a separate dosage regimen or disease indication.

What does the patent not cover?

US 8,067,472 does not, on its face, cover the following regimens unless they independently satisfy the claim language:

Regimen or use	Likely relationship to US 8,067,472
100 mg once daily	Outside the stated dose
200 mg once daily	Outside the stated dose
400 mg twice daily	Outside the stated dose
200 mg twice daily for non-Hodgkin's lymphoma	Outside claim 3 because the disease differs
400 mg once daily for Hodgkin's lymphoma	Outside claim 1 because the disease differs
Intravenous SAHA	Outside the oral-route limitation
Topical vorinostat	Outside the oral-route limitation
Vorinostat for cutaneous T-cell lymphoma	Not expressly covered unless the disease is also within the ordinary meaning of non-Hodgkin's lymphoma and all other limitations are met
Vorinostat for multiple myeloma	Not expressly claimed
Vorinostat for solid tumors	Not expressly claimed
Vorinostat in combination therapy	Not excluded if the claimed dose and disease limitations are otherwise met; the claims do not require monotherapy

The most important construction issue is disease classification. Cutaneous T-cell lymphoma is generally a type of non-Hodgkin's lymphoma, but the patent's clinical and prosecution record could affect whether the claims are applied to that subtype. A generic or clinical operator would need to assess the intrinsic record, prosecution history, and relevant jurisdictional standards before treating the classification as dispositive.

When did US Patent 8,067,472 expire?

US Patent 8,067,472 issued on November 29, 2011. Public patent records identify an ordinary expiration date in March 2025, based on the patent's priority and filing history. No current enforceable exclusion right should be assumed from this patent after that date.

Event	Date or status
Relevant priority or filing history	March 2004 priority period identified in patent records
US patent grant	November 29, 2011
Patent number	US 8,067,472 B2
Ordinary term	Approximately 20 years from the relevant nonprovisional filing date
Ordinary expiration	Approximately March 11, 2025
Current status	Expired by term, absent an unusual term adjustment or other record-specific extension

The patent's expiration does not retroactively eliminate infringement exposure for conduct occurring before expiration. It does remove the patent as a continuing barrier to future conduct after expiration.

What is the FDA and Orange Book status of vorinostat?

The FDA approved Zolinza, containing vorinostat, on October 6, 2006, for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients with progressive, persistent, or recurrent disease after two systemic therapies.[2]

The approved product is an oral capsule containing 100 mg of vorinostat. The FDA labeling identifies a recommended dosage of 400 mg once daily, with dose reduction to 300 mg once daily for certain toxicities or inability to tolerate treatment.[2]

Does the FDA label match the patent claims?

The FDA-approved 400 mg once-daily regimen aligns with the dose structure in claim 1, but the approved indication is cutaneous T-cell lymphoma rather than the broader "non-Hodgkin's lymphoma" wording used in the patent.

Claim 3, which covers 200 mg twice daily for Hodgkin's lymphoma, does not correspond to the principal Zolinza FDA indication. It appears directed to clinical findings involving vorinostat treatment in lymphoma patients rather than the approved labeled regimen.

Is US 8,067,472 an Orange Book barrier?

An Orange Book listing matters most when a patent claims the approved drug, an approved formulation, or an approved method of use. A patent claiming an unapproved indication may not create a conventional Orange Book blocking position for an ANDA directed to the approved label.

The relevant assessment is:

Issue	Assessment
Approved product	Zolinza, vorinostat capsules
Approved strength	100 mg capsules
Principal FDA indication	Cutaneous T-cell lymphoma
FDA-approved dose	400 mg once daily
Patent's principal dose claim	400 mg once daily
Patent's express disease language	Non-Hodgkin's lymphoma and Hodgkin's lymphoma
Orange Book relevance	Depends on the listed patent use code and relationship to the approved labeling
Current effect of US 8,067,472	No continuing term-based barrier after expiration

The FDA Orange Book should be read together with the patent listing history and use code. A listing would not revive an expired patent or extend its term.[3]

What patent landscape surrounds vorinostat and Zolinza?

The US 8,067,472 patent is one part of a broader vorinostat estate. The principal categories are compound patents, formulation and pharmaceutical composition patents, treatment-method patents, and regulatory exclusivity.

Which patents protected the vorinostat compound?

The original SAHA compound and related hydroxamic acid chemistry were protected by earlier patents associated with Columbia University and subsequent commercial development. Those earlier compound rights had substantially earlier expiration dates than US 8,067,472 because they were filed closer to the initial discovery and development period.

The commercial consequence was predictable: the compound itself became vulnerable to generic development before later regimen patents expired. A later method patent can protect a clinical use or dose schedule, but it does not recreate composition-of-matter exclusivity for the active ingredient.

What formulation patents protect vorinostat?

Formulation protection may cover:

capsule compositions;
particle-size distributions;
excipient combinations;
dissolution profiles;
stability characteristics;
solid-state forms; and
manufacturing processes.

US 8,067,472 does not claim a formulation. A product could avoid this patent while still requiring a separate formulation analysis. Conversely, a generic product may use a different formulation and avoid formulation claims while remaining subject to method-of-use issues during the relevant patent term.

Are there manufacturing or process barriers?

The claims provided do not cover manufacturing. They do not require a synthesis route, purification step, crystallization condition, particle size, or packaging configuration.

Vorinostat is a relatively established small molecule. Manufacturing risk is therefore more likely to arise from:

quality specifications;
residual solvents;
impurity control;
process validation;
bioequivalence;
stability;
capsule filling; and
any surviving process or solid-state patent.

These issues are separate from the treatment-method claims in US 8,067,472.

When did FDA exclusivity for Zolinza expire?

Zolinza received FDA orphan-drug designation and approval for a rare lymphoma indication. Orphan-drug exclusivity generally lasts seven years from approval for the approved indication, subject to the statutory framework and possible exceptions. For an October 6, 2006 approval, the principal seven-year period would have run to October 6, 2013.[2][4]

That exclusivity was narrower than patent protection. It did not prevent approval of a product for an indication outside the protected orphan indication, and it did not prevent all patent challenges. By the time of generic development, the relevant FDA exclusivity period had ended.

Exclusivity category	Relevant date	Commercial impact
FDA approval	October 6, 2006	Established Zolinza regulatory approval
Orphan-drug exclusivity	Approximately October 6, 2013	Protected the designated indication for seven years
US 8,067,472 patent term	Approximately March 11, 2025	Protected specified lymphoma dosing methods during its term
Current status	Post-expiration	Patent and orphan exclusivity no longer block new entry

Were there Paragraph IV challenges to vorinostat?

Vorinostat is an ANDA-eligible small molecule, not a biologic. Generic applicants could challenge listed patents through Paragraph IV certifications or use a Paragraph III certification for patents that had expired.

A Paragraph IV challenge would require the applicant to certify that a listed patent is invalid, unenforceable, or not infringed. The most credible design-around arguments for the claims in US 8,067,472 would have involved:

a different dose;
a different dosing frequency;
a nonclaimed disease indication;
a label that omits the patented use;
a section viii carve-out for a method-of-use patent; or
a product whose labeling does not encourage the claimed regimen.

The patent's limited claim set reduced the risk that every vorinostat generic would necessarily infringe. A generic applicant could pursue an indication-limited label, where legally available, or rely on a noninfringing regimen and avoid promoting the patented use.

Public patent and regulatory records do not establish a continuing litigation barrier from US 8,067,472 after its 2025 expiration. The principal business risk shifted from patent litigation to ordinary ANDA approval, supply, pricing, and market-share competition.

Which companies compete in the vorinostat generic market?

The competitive field includes the originator product and ANDA sponsors that obtained or pursued approval for generic vorinostat capsules. Generic competition is structurally different from biologic competition because:

no biosimilar pathway is required;
the active ingredient is chemically defined;
approval generally proceeds through an ANDA;
bioequivalence is the central clinical standard; and
the generic may rely on the reference product's safety and efficacy findings.

The likely competitive variables are manufacturing scale, API sourcing, capsule supply, wholesaler contracts, and payer substitution. A single generic entrant may have limited commercial impact, while several approved suppliers can rapidly compress price and originator volume.

Is there biosimilar risk for vorinostat?

No. Vorinostat is a small-molecule drug, not a biologic. The relevant competitor pathway is generic substitution through an ANDA, not a biosimilar application under the Public Health Service Act.

The competitive risk is therefore generic erosion rather than biosimilar interchangeability. Any remaining branded value would depend on supply reliability, contracting, clinical familiarity, and niche oncology demand rather than biologic manufacturing complexity.

How strong is the patent estate for vorinostat?

The estate was strongest during the period when the compound, regulatory exclusivity, formulation rights, and method patents overlapped. Its present strength is materially lower because the cited regimen patent has expired and the FDA orphan-exclusivity period ended years earlier.

Estate component	Strength during launch period	Current position
Compound protection	Strong but early-expiring	Expired
FDA orphan exclusivity	Strong for designated indication	Expired
400 mg once-daily method	Relevant to labeled dosing and lymphoma treatment	US 8,067,472 expired
200 mg twice-daily Hodgkin's method	Narrow clinical-use protection	US 8,067,472 expired
Formulation protection	Potentially product-specific	Requires separate patent review
Manufacturing protection	Potentially process-specific	Requires separate patent review
Biosimilar barrier	Not applicable	Not applicable
Generic entry barrier	Potentially meaningful before patent expiry	Primarily regulatory and commercial

The patent was narrow but commercially relevant. Claim 1 tracked the standard 400 mg once-daily dose used in the FDA label, creating potential method-of-use exposure for conduct involving the patented lymphoma population during the patent term. Claim 3 was narrower because it required both Hodgkin's lymphoma and 200 mg twice-daily dosing.

What generic launch scenarios existed?

Before expiration, the main scenarios were:

A generic applicant accepted the patent term and launched after expiration.
The applicant filed a Paragraph IV certification and obtained a launch opportunity after litigation or settlement.
The applicant used a section viii statement to omit a patented use from the label.
The applicant launched a product with labeling that did not encourage the claimed regimen.
The applicant entered at risk after resolving or accepting litigation exposure.

After the ordinary expiration of US 8,067,472, the patent-specific launch barrier disappeared. Any remaining delay would arise from other listed patents, regulatory requirements, commercial strategy, or supply constraints.

What litigation and settlement issues matter?

The relevant litigation questions are:

whether US 8,067,472 was listed in the Orange Book during the ANDA challenge period;
whether the listed use code matched the proposed generic label;
whether an ANDA sponsor filed a Paragraph IV certification;
whether the patent owner sued within the statutory window;
whether a 30-month stay applied;
whether the parties entered a launch-date settlement; and
whether any settlement included a supply, license, or authorized-generic provision.

No continuing litigation effect should be attributed to this patent solely because it once existed. Any settlement tied to a now-expired patent would have to be reviewed for independent contractual obligations, but the patent itself no longer supplies prospective exclusivity.

Key Takeaways

US 8,067,472 is a dosing and method-of-treatment patent for vorinostat, not a compound or formulation patent.
Claim 1 covers oral 400 mg once-daily SAHA treatment for non-Hodgkin's lymphoma.
Claim 3 covers oral 200 mg twice-daily SAHA treatment for Hodgkin's lymphoma.
Claims 2 and 4 add little practical scope because the independent claims already identify SAHA.
The patent does not claim every vorinostat use, every dose, or every formulation.
The patent's ordinary term expired in approximately March 2025.
Zolinza was FDA-approved on October 6, 2006, for cutaneous manifestations of cutaneous T-cell lymphoma.
FDA orphan-drug exclusivity ran approximately through October 6, 2013.
Vorinostat faces generic, not biosimilar, competition.
Remaining commercial risk depends on separate compound, formulation, process, Orange Book, regulatory, and contractual rights.

FAQs

Does US 8,067,472 cover the Zolinza 100 mg capsule?

The patent claims a 400 mg daily treatment regimen, not the 100 mg capsule as a product. Four 100 mg capsules could be used to administer the claimed daily dose, but the patent does not independently claim the capsule formulation.

Does taking vorinostat 400 mg once daily infringe the patent?

During the patent term, infringement depended on the disease, product, route, and conduct involved. The claimed regimen was 400 mg orally once daily for non-Hodgkin's lymphoma. After patent expiration, the patent no longer creates prospective infringement liability for that regimen.

Does the patent cover vorinostat for cutaneous T-cell lymphoma?

The patent expressly refers to non-Hodgkin's lymphoma and Hodgkin's lymphoma. Cutaneous T-cell lymphoma is generally classified within the non-Hodgkin's lymphoma family, but application of the claim to a specific subtype would depend on claim construction, clinical facts, and the patent record.

Can a generic company sell vorinostat for unpatented indications?

A generic applicant may seek approval with a label that omits patented uses where the FDA's section viii framework permits the carve-out. The commercial and legal analysis depends on the Orange Book use code, proposed labeling, promotional conduct, and any separate patents.

Does expiration of US 8,067,472 mean all vorinostat patents have expired?

No. Expiration of this regimen patent does not establish the status of every patent relating to vorinostat. Separate formulation, solid-state, process, packaging, or other method patents require independent review.

References

United States Patent and Trademark Office. (2011). US Patent No. 8,067,472 B2: Methods for treating lymphoma using suberoylanilide hydroxamic acid.
U.S. Food and Drug Administration. (2023). Zolinza (vorinostat) prescribing information. Merck & Co., Inc.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Orphan drug designation and approval database.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	462426	⤷ Start Trial
Australia	2003213684	⤷ Start Trial
Australia	2004266169	⤷ Start Trial
Australia	2004283717	⤷ Start Trial
Australia	2008246251	⤷ Start Trial
Australia	2009201668	⤷ Start Trial
Brazil	0308250	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,067,472

Summary for Patent: 8,067,472