U.S. Patent 9,724,330: Apremilast Method-of-Treatment Claims, Scope, Expiration and Patent Landscape

U.S. Patent 9,724,330 protects methods of treating autoimmune disease with stereomerically enriched apremilast, the active ingredient in Otezla. The patent is focused on the drug’s therapeutic use, oral dosage forms, dose ranges, dosing frequency, tablet and capsule strengths, and enantiomeric purity. It does not principally claim the apremilast molecule as a chemical compound, a manufacturing process, or a particular polymorph.

The broadest independent claim covers administering therapeutically effective apremilast to a patient with an autoimmune disease. The most commercially relevant dependent claims cover oral tablets containing 10 mg or 20 mg administered twice daily, and a 100 mg once-daily regimen.

What drug does U.S. Patent 9,724,330 cover?

The claimed compound is the positive enantiomer of apremilast:

2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.

Apremilast is an orally administered phosphodiesterase-4 inhibitor. The FDA approved Otezla for psoriatic arthritis in 2014 and later expanded the label to include plaque psoriasis and oral ulcers associated with Behçet's disease. The commercial product is marketed by Amgen after its acquisition of Otezla from Celgene/Bristol Myers Squibb. [1,2]

Item	Information
Active ingredient	Apremilast
Brand	Otezla
Original developer	Celgene
Current commercial owner	Amgen
Drug class	Phosphodiesterase-4 inhibitor
Primary dosage form	Oral tablet
Commercial strengths	10 mg, 20 mg and 30 mg tablets
FDA approval	2014
Approved indications	Psoriatic arthritis, plaque psoriasis, Behçet's disease
Patent at issue	U.S. 9,724,330
Patent type	Method of treatment

The claim language uses “stereomerically pure,” although the conventional term is “stereomerically pure” or “enantiomerically enriched,” depending on the intended analytical definition. The claims expressly set purity thresholds of greater than 90%, greater than 95%, greater than 97%, and approximately 98.7% by weight of the (+) isomer.

What are the independent claims in U.S. Patent 9,724,330?

Claim 1 is the principal independent claim. It requires:

A patient who has an autoimmune disease;
Administration of the claimed (+)-apremilast stereoisomer; and
A therapeutically effective amount.

The claim does not limit the autoimmune disease to psoriasis, psoriatic arthritis, or Behçet's disease. On its face, it covers treatment of autoimmune disease broadly. The enforceable scope would still depend on the patent specification, written-description support, claim construction, prosecution history, and the factual fit between the accused disease and the claimed therapeutic use.

Claim 2 depends from claim 1 and requires concurrent administration of an antihistamine, anti-inflammatory drug, nonsteroidal anti-inflammatory drug, or steroid.

Claims 3 through 11 narrow the method by adding:

Mammalian patients;
Parenteral, transdermal, mucosal, nasal, buccal, sublingual, or oral administration;
Oral tablets or capsules;
Daily doses from 1 mg to 1,000 mg;
Narrower dose bands of 5 mg to 500 mg and 10 mg to 200 mg;
Twice-daily administration in equally divided doses; and
Specified NSAIDs, including ibuprofen, naproxen, diclofenac, meloxicam and related agents.

Claims 12 through 14 impose purity thresholds. Claims 15 through 22 identify 10 mg, 20 mg, 25 mg and 50 mg capsule or tablet strengths.

Claims 23 through 33 are more commercially targeted. They require approximately 98.7% (+) isomer and then specify oral tablet administration, twice-daily 10 mg or 20 mg dosing, or a once-daily 100 mg dose.

How broad is the scope of the patent claims?

The patent has broad disease and route language but narrower compound and treatment limitations.

Claim feature	Breadth	Commercial significance
Autoimmune disease	Broad	Reaches diseases beyond the approved Otezla indications if supported by the patent
(+)-apremilast	Narrow	Excludes racemic material and potentially excludes products outside the claimed purity range
Therapeutically effective amount	Broad but functional	Requires proof of treatment efficacy or intended therapeutic use
Oral administration	Narrower	Maps directly to the Otezla product
Tablet or capsule	Narrower	Relevant to generic finished-dose products
10 mg and 20 mg strengths	Narrow	Directly overlaps Otezla titration strengths
100 mg once-daily dose	Narrow	Does not correspond to the standard approved Otezla maintenance regimen
Greater than 90% to approximately 98.7% (+) isomer	Variable	Creates purity-based claim positions
Combination with NSAID or steroid	Narrow	Potentially relevant to combination-treatment protocols

The most important practical distinction is between literal claim scope and infringement risk. A generic apremilast tablet could satisfy the compound, oral administration, tablet, and dose limitations. But infringement of a method-of-use claim generally requires proof that the product is made, sold, or used with the claimed treatment method. Label instructions, prescribing information, promotional materials, physician knowledge, and induced-infringement evidence can become central.

Which Otezla dosing regimens overlap with the patent?

The standard Otezla regimen begins with a five-day titration schedule and reaches a maintenance dose of 30 mg twice daily. The patent expressly claims several strengths that are used during titration or that could be used in alternative regimens, including 10 mg and 20 mg tablets.

The claim set does not expressly identify the standard 30 mg twice-daily maintenance dose in the claims supplied. That omission matters. Claims 26 and 27 cover 10 mg and 20 mg tablets administered twice daily, while claim 29 covers a 100 mg once-daily tablet.

Patent claim	Dose or regimen	Relationship to Otezla
Claims 7-9	1-1,000 mg/day, with narrower ranges	Broad dose coverage
Claim 11	Twice daily, equally divided doses	General dosing limitation
Claims 15-18	10, 20, 25 or 50 mg capsules	Dosage-form coverage
Claims 19-22	10, 20, 25 or 50 mg tablets	Direct tablet coverage
Claims 26-27	10 mg or 20 mg tablet twice daily	Directly relevant to titration or alternative dosing
Claim 29	100 mg tablet once daily	Alternative regimen
Claims 30-33	1-1,000 mg/day and 100 mg/day	Broad and specific daily-dose positions

The strongest commercial overlap is therefore likely to arise from generic labeling and use instructions involving oral apremilast tablets, rather than from the molecule alone.

When does U.S. Patent 9,724,330 expire?

The patent’s ordinary expiration date is expected to fall in November 2028, based on the underlying priority framework associated with the patent family. The exact enforceable date should be determined from the USPTO patent-term calculation, including any patent-term adjustment, terminal disclaimer, or other prosecution-related modification. [3]

Event	Date or period
Earliest priority framework	2008
Patent issuance	August 8, 2017
Expected statutory expiration	November 2028
FDA-approved product	Otezla
Regulatory exclusivity	Separate from patent term and generally shorter than the patent period

The patent is a method-of-treatment patent. Its expiration date does not itself determine when an ANDA applicant may launch. Launch risk also depends on other listed patents, Paragraph IV litigation, settlement agreements, regulatory exclusivity, and whether the generic label would induce infringement.

What is the Orange Book status of U.S. Patent 9,724,330?

The FDA Orange Book is the relevant source for determining whether the patent is listed against the Otezla NDA and whether the NDA holder has submitted a use code. Orange Book listing is important because it can trigger the statutory Paragraph IV notice and litigation framework for an ANDA applicant. [4]

A method-of-use patent may be listed with a use code that identifies the approved indication or a method of using the drug. An ANDA applicant can seek a section viii carve-out for a patented use if the proposed label omits the protected method. That strategy is less effective when the patent claims overlap with the remaining label or when the proposed labeling encourages the patented use.

For U.S. 9,724,330, the principal diligence questions are:

Whether the patent is currently listed against NDA 205437;
The submitted expiration date;
The associated FDA use code;
Whether the listed use can be carved out under section viii;
Whether the generic label includes oral dosing or indications covered by the claims; and
Whether the NDA holder has submitted related continuation or divisional patents.

The patent number alone does not establish the current Orange Book listing status. That status is maintained by the FDA and can change through patent-listing updates.

What Paragraph IV challenges affect the patent?

A Paragraph IV certification states that a listed patent is invalid, unenforceable, or will not be infringed by the proposed ANDA product. If the NDA holder receives timely notice, filing an infringement action within the statutory period can trigger a 30-month stay of final FDA approval, subject to statutory exceptions. [5]

For this patent, a generic applicant would likely evaluate several positions:

The claims are not infringed because the proposed label does not instruct treatment of a claimed autoimmune disease.
The product does not meet the claimed stereomeric purity threshold.
The accused regimen does not satisfy the claimed dose, frequency, tablet, or capsule limitation.
The claims are invalid for lack of novelty, obviousness, written description, enablement, indefiniteness, or lack of patentable subject matter.
The patent is unenforceable because of inequitable conduct or prosecution-related issues.
The patent can be avoided through a section viii labeling carve-out.

The principal vulnerability of the claims is their method-of-use character. A product claim would generally be easier to enforce against any commercial apremilast product. A method claim requires a closer connection between the generic label or conduct and the patented treatment method.

The principal strength is the detailed claim layering. Even if broad claim 1 is challenged, the tablet, dose, purity, and dosing-frequency claims create multiple fallback positions.

How strong is the patent estate for apremilast?

The apremilast estate historically has included several patent categories:

Patent category	Function
Compound patents	Protect apremilast or related chemical structures
Enantiomer patents	Protect the active stereoisomer and stereochemical purity
Method-of-treatment patents	Protect use in autoimmune and inflammatory diseases
Formulation patents	Protect tablets, excipients, release characteristics, or solid forms
Process patents	Protect synthesis, resolution, purification, or manufacturing steps
Regulatory listings	Create ANDA certification and litigation exposure

U.S. 9,724,330 is strongest as a use patent directed to oral apremilast treatment. It is not a complete substitute for compound, formulation, or process protection. A generic company can potentially avoid one category while remaining exposed to another.

The patent is more valuable when the commercial product’s label directly recites the claimed disease, route, dose, and dosage form. It is less powerful against an ANDA that uses a carefully carved-out label or a dosing regimen outside the narrow dependent claims.

What formulations are protected by the patent?

The supplied claims cover tablets and capsules but do not define a particular excipient system, coating, dissolution profile, particle-size distribution, or polymorphic form. Claims 6 and 15 through 22 are dosage-form claims in the method-of-treatment context, not stand-alone composition-of-matter claims.

This distinction limits the formulation protection:

A tablet containing apremilast may fall within the method claims when used as directed for the claimed disease.
The patent does not, from the supplied claims, independently prohibit manufacturing every apremilast tablet.
A formulation patent with composition claims could create a separate barrier even if the method patent were invalidated.
A generic product could face infringement risk from the label and intended use even if its excipient formulation differs.

Does biosimilar risk apply to Otezla?

No. Otezla is a small-molecule drug, not a biologic. The relevant competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Biologics Price Competition and Innovation Act.

The competitive risks are therefore:

ANDA filings;
Paragraph IV certifications;
Section viii carve-outs;
Patent litigation;
Authorized generic competition;
Formulation or process workarounds; and
Post-expiration generic entry.

Which companies are challenging Otezla patents?

A reliable answer requires current FDA Orange Book data, ANDA notices, PACER litigation records, and settlement disclosures. Patent records alone do not establish the identity or current status of every generic challenger. Publicly reported generic activity should be analyzed separately from the validity of U.S. 9,724,330.

Potential entrants would include major ANDA manufacturers with apremilast development programs, but an applicant’s formulation development or Paragraph IV filing is not established merely by the existence of this patent.

What is the commercial exposure if the patent is upheld?

Amgen reported Otezla sales of approximately $3.1 billion in 2023. [6] The commercial exposure associated with U.S. 9,724,330 is therefore material, but the patent captures only one portion of the total exclusivity position.

The relevant launch scenarios are:

Scenario	Commercial effect
All relevant patents remain enforceable through 2028	Generic entry may be delayed until settlement or expiration
U.S. 9,724,330 is invalidated but other patents remain	Limited effect if compound or formulation patents survive
Generic label carves out the patented use	Earlier approval may be possible
Method claims are not infringed	Reduced litigation leverage
Multiple patents expire or settle together	Entry may occur near the negotiated date
Authorized generic launches	Price erosion can begin without an independent ANDA launch

Key Takeaways

U.S. 9,724,330 is a method-of-treatment patent for stereomerically enriched (+)-apremilast.
Claim 1 broadly targets treatment of autoimmune disease, but infringement requires the claimed drug, patient, disease, and therapeutic administration.
The commercially important dependent claims cover oral tablets, capsules, 10 mg and 20 mg strengths, twice-daily administration, and a 100 mg once-daily regimen.
The patent does not, based on the supplied claims, independently claim the apremilast molecule, a specific excipient formulation, or a manufacturing process.
The expected statutory expiration is in November 2028, subject to the official USPTO term calculation.
Paragraph IV and section viii strategies are central because the patent claims methods of use rather than the drug product alone.
Otezla is a small molecule, so biosimilar rules do not apply.
The patent’s commercial strength depends on the remaining Otezla patent estate, Orange Book use codes, generic labeling, and any settlement agreements.
Otezla’s multibillion-dollar annual sales make generic-entry timing commercially significant.

FAQs

Is U.S. Patent 9,724,330 a compound patent for apremilast?

No. The supplied claims are method claims. They require administering the specified stereomerically enriched apremilast compound to treat autoimmune disease.

Does the patent cover the standard 30 mg twice-daily Otezla maintenance dose?

The supplied claims do not expressly recite a 30 mg twice-daily tablet regimen. Broad daily-dose and twice-daily claims may still be relevant, but the exact infringement analysis depends on claim construction and the accused product’s labeling.

Can a generic company sell apremilast after carving out the patented indication?

Potentially. A section viii carve-out may permit approval for nonpatented uses if the labeling omits the protected method and does not encourage its use. The FDA use code and the remaining label determine whether that strategy is viable.

Is a different apremilast polymorph outside the patent?

Not necessarily. The supplied claims focus on the stereomeric composition and method of administration, not a named polymorph. A different solid form could still satisfy the claims if it contains the claimed (+) isomer and is administered according to the claimed method.

Does patent invalidity eliminate all Otezla exclusivity?

No. Other compound, formulation, process, method-of-use, or regulatory protections may remain enforceable even if U.S. 9,724,330 is invalidated.

References

U.S. Food and Drug Administration. (2014). FDA approves new treatment for psoriatic arthritis.
U.S. Food and Drug Administration. (2023). Otezla prescribing information. Amgen Inc.
United States Patent and Trademark Office. (2017). U.S. Patent No. 9,724,330, Methods of treating autoimmune diseases.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulations and patent certifications.
Amgen Inc. (2024). 2023 annual report.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2962690	⤷ Start Trial	300994	Netherlands	⤷ Start Trial
European Patent Office	2962690	⤷ Start Trial	LUC00125	Luxembourg	⤷ Start Trial
European Patent Office	2962690	⤷ Start Trial	122019000070	Germany	⤷ Start Trial
European Patent Office	2962690	⤷ Start Trial	CA 2019 00033	Denmark	⤷ Start Trial
European Patent Office	2962690	⤷ Start Trial	2019C/008	Belgium	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,724,330

Summary for Patent: 9,724,330