Details for Patent: 10,092,541

Which drugs does patent 10,092,541 protect, and when does it expire?

Patent 10,092,541 protects OTEZLA XR and OTEZLA and is included in two NDAs.

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

This patent has two patent family members in two countries.

Summary for Patent: 10,092,541

Title:	Methods for the treatment of diseases ameliorated by PDE4 inhibition using dosage titration of apremilast
Abstract:	Methods of treating, managing or preventing diseases ameliorated by inhibiting PDE4 such as psoriasis, ankylosing spondylitis, Behcet's disease, rheumatoid arthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis are disclosed. Specific methods encompass the administration of apremilast in specific dosage titration schedule, alone or in combination with a second active agent.
Inventor(s):	Robert Day
Assignee:	Amgen Inc
Application Number:	US14/826,027
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,092,541
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 10,092,541: Apremilast Claims, Exclusivity, Litigation Risk, and Patent Landscape

US 10,092,541 protects a titration-and-maintenance dosing regimen for stereomerically pure apremilast, the active ingredient in Otezla. The patent does not claim apremilast as a chemical compound. It claims administration of the (+) enantiomer to patients with specified inflammatory diseases, using a five-day dose escalation followed by either 60 mg/day or a broader 40-100 mg/day maintenance range.

The principal commercial exposure is Otezla’s labeled 60 mg/day regimen for psoriasis, psoriatic arthritis, and Behcet's disease. The patent also recites ankylosing spondylitis, rheumatoid arthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis, although those indications are not all FDA-approved uses of Otezla.

What drug and active ingredient does US 10,092,541 protect?

The claimed molecule is apremilast, chemically identified in the patent as:

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

The claims are directed specifically to the stereomerically pure (+) isomer. Apremilast is a small-molecule phosphodiesterase-4 inhibitor. Otezla is administered orally in tablet form and is marketed by Amgen in the United States.[1]

Attribute	Patent and product position
Patent	US 10,092,541 B2
Active ingredient	Apremilast
Claimed stereochemistry	(+) enantiomer
Drug class	PDE-4 inhibitor
Product	Otezla
Dosage form	Oral immediate-release tablet
FDA application	NDA 205437
Patent owner and commercial rights	Amgen, following the Otezla asset acquisition from Celgene
Patent issue date	October 9, 2018
Principal protection	Method of treatment and dosing regimen
Expected patent expiration	September 24, 2028, subject to the official USPTO term calculation and any applicable adjustments

The patent is separate from earlier patents that claim apremilast’s chemical structure, enantiomeric forms, pharmaceutical compositions, and other therapeutic uses.

What are the independent claims in US 10,092,541?

Claims 1 through 14 are the substantive treatment claims. They use a common regimen and vary primarily by disease and maintenance dose.

Claims 1, 3, 5, 7, 9, 11, and 13

These claims cover treatment of:

• Psoriasis
• Ankylosing spondylitis
• Behcet's disease
• Rheumatoid arthritis
• Atopic dermatitis
• Crohn's disease
• Ulcerative colitis

The required initial titration is:

Day	Morning dose	Afternoon dose	Total daily dose
1	10 mg	None	10 mg
2	10 mg	10 mg	20 mg
3	10 mg	20 mg	30 mg
4	20 mg	20 mg	40 mg
5	20 mg	30 mg	50 mg
6 onward	N/A	N/A	40-100 mg/day

The maintenance dose in these claims is expressed as a range of about 40 mg/day to about 100 mg/day.

Claims 2, 4, 6, 8, 10, 12, and 14

These claims cover the same seven diseases and the same five-day titration, but require a fixed maintenance regimen beginning on day six:

• 30 mg in the morning; and
• 30 mg in the afternoon.

That is a total of 60 mg/day.

The 60 mg/day claims closely track the approved Otezla dosing schedule. FDA labeling directs dose escalation over the first five days to reduce gastrointestinal adverse reactions, with 30 mg twice daily beginning on day six.[2]

How narrow are the dosing claims?

The claims are narrow in their literal elements but commercially significant because the claimed regimen matches the labeled product regimen.

A potentially infringing administration must satisfy the following elements:

1. The active ingredient must be the (+) apremilast enantiomer.
2. The patient must have one of the listed diseases.
3. The initial five-day titration must follow the stated morning and afternoon schedule.
4. The maintenance regimen must fall within the claimed dose range or equal 30 mg twice daily.
5. For dependent claims, the product must satisfy the stated purity, dosage-form, salt, or solvate limitation.

“Consisting of” limits the claim scope

The claims use “consisting of” in describing the treatment method. That language generally operates as a closed transition. It strengthens an argument that the claimed method requires the specified regimen and does not readily encompass additional unrecited treatment steps.

The claims do not expressly require:

• A particular treatment duration;
• A particular tablet strength;
• A particular excipient;
• A particular manufacturing process;
• A particular pharmacokinetic profile;
• Concomitant administration with another drug; or
• A particular severity score or clinical response.

The claims are therefore regimen-specific rather than formulation-process claims.

The broad maintenance range creates the largest literal coverage

Claims 1, 3, 5, 7, 9, 11, and 13 cover “about 40 mg/day” to “about 100 mg/day.” That language could reach a variety of total daily doses, depending on how “about” is construed and whether the dose is administered once or in divided doses.

Claims 2, 4, 6, 8, 10, 12, and 14 are more specific because they require 30 mg twice daily. A generic product labeled for the same schedule would face direct method-of-use exposure if the patent remains enforceable and the relevant use code is asserted.

What do claims 15 through 24 add?

Claims 15 through 24 are dependent claims that create narrower fall-back positions.

Claims	Added limitation	Commercial relevance
15	More than about 90% (+) isomer	Low practical narrowing because pharmaceutical apremilast is normally highly enantiopure
16	More than about 95% (+) isomer	Likely met by commercial product
17	More than about 96% (+) isomer	Likely met by commercial product
18	More than about 97% (+) isomer	Likely met by commercial product
19	More than about 98% (+) isomer	Likely met by commercial product
20	More than about 99% (+) isomer	Potentially important analytical limitation
21	Tablet form	Directly aligned with Otezla
22	Substantially free of salt or solvate	Covers the free form
23	Pharmaceutically acceptable salt	Covers salt forms
24	Pharmaceutically acceptable solvate	Covers solvate forms

The purity claims are cumulative dependent claims. A product containing more than 99% of the (+) isomer would also fall within the lower purity thresholds, assuming the other limitations are met.

Claim 21 is commercially important because Otezla is a tablet. Claims 22 through 24 seek to prevent design-around through routine solid-state or pharmaceutical-form changes. Their practical strength depends on whether the marketed or proposed generic product uses the free form, a salt, or a solvate and on the construction of “substantially free.”

What FDA-approved indications are covered?

Otezla’s principal FDA-approved indications include:

• Moderate-to-severe plaque psoriasis in candidates for phototherapy or systemic therapy;
• Active psoriatic arthritis; and
• Oral ulcers associated with Behcet's disease.[2]

US 10,092,541 claims those disease areas through claims 1, 2, 5, and 6. The other claimed indications are broader than the current core Otezla label.

Claimed indication	FDA-approved Otezla status
Psoriasis	Approved
Psoriatic arthritis	Not expressly recited in the supplied claims
Behcet's disease	Approved for oral ulcers associated with Behcet's disease
Ankylosing spondylitis	Not approved for Otezla
Rheumatoid arthritis	Not approved for Otezla
Atopic dermatitis	Not approved for Otezla
Crohn's disease	Not approved for Otezla
Ulcerative colitis	Not approved for Otezla

The absence of psoriatic arthritis from the supplied claims is commercially notable. Other Otezla patents and regulatory materials may address that indication, but US 10,092,541 should not be characterized as a psoriatic-arthritis patent based solely on these claims.

What patents protect Otezla and apremilast beyond US 10,092,541?

The Otezla patent estate has historically included several patent families covering different layers of protection:

Protection layer	Typical subject matter	Strategic function
Composition of matter	Apremilast and related isoindolinone derivatives	Core molecule protection
Stereochemistry	(+) enantiomer and enantiomeric purity	Excludes racemic or opposite-enantiomer strategies
Pharmaceutical composition	Tablets, excipients, dosage forms	Product-level protection
Method of treatment	Psoriasis, psoriatic arthritis, Behcet's disease and other inflammatory conditions	Use-specific enforcement
Dosing regimen	Five-day titration followed by 60 mg/day	Directly tracks the FDA label
Solid-state protection	Polymorphs, salts, solvates, crystallinity	Manufacturing and formulation barriers
Risk-management systems	Product distribution and patient-safety controls	Regulatory and commercial barriers rather than conventional composition claims

The earliest apremilast composition patents have shorter remaining terms than later dosing and formulation patents. A generic applicant may therefore avoid an expired composition patent but still face later method, formulation, or solid-state patents.

When does US 10,092,541 lose exclusivity?

The stated patent expiration date is September 24, 2028. The relevant exclusivity timeline is:

Date or period	Event
2014	FDA approval of Otezla for psoriatic arthritis and plaque psoriasis
2018	Issuance of US 10,092,541
2019	Otezla rights transferred from Celgene to Amgen as part of the Celgene asset divestiture
2019	FDA approval for oral ulcers associated with Behcet's disease
September 24, 2028	Expected expiration of US 10,092,541
After patent expiry	Potential unimpeded generic use of the claimed regimen, subject to other unexpired patents, regulatory exclusivities, and court orders

The patent term is distinct from FDA regulatory exclusivity. Otezla’s original new-chemical-entity exclusivity expired years before the expected patent expiry. The remaining barrier is primarily patent-based rather than NCE exclusivity-based.

No biosimilar exclusivity analysis applies because apremilast is a synthetic small molecule regulated through the ANDA pathway, not a biologic regulated through the BPCIA pathway.

What is the Orange Book status of US 10,092,541?

US 10,092,541 is part of the Otezla patent landscape and is relevant to Orange Book-listed method-of-use protection. Orange Book listing does not establish validity or infringement. It identifies patents submitted by the NDA holder as covering the approved drug, its composition, or an approved method of use.[3]

The practical effect of an Orange Book-listed method patent is:

• An ANDA applicant must address the listed patent;
• A Paragraph IV certification can trigger patent litigation;
• A timely infringement action can create a 30-month stay of ANDA approval under the Hatch-Waxman Act;
• A Section viii statement may be available when the generic omits the patented indication from its labeling.

The ability to use a Section viii carve-out depends on the listed patent’s use code and the scope of the generic label. A generic seeking approval for an indication or regimen that remains within the patent’s use code cannot rely on a simple carve-out.

Which companies are challenging Otezla exclusivity?

Generic competition is expected to come from ANDA applicants rather than biosimilar developers. Publicly reported Otezla generic activity has involved multiple companies, including major generic manufacturers that have pursued abbreviated approval and patent challenges.

The principal competitive issue is whether an ANDA applicant:

1. Certifies Paragraph IV against US 10,092,541;
2. Accepts a later approval date;
3. Carves out the patented method from its labeling; or
4. Challenges the patent in litigation or inter partes review.

A Paragraph IV challenge does not itself invalidate the patent. It creates litigation risk and may accelerate a negotiated launch date through a settlement agreement.

What generic entry risks exist for apremilast?

Scenario 1: Launch after September 2028

This is the lowest-risk path if the generic product does not practice any other unexpired Otezla patent. The generic could use the same active ingredient and seek approval for the same broad disease categories after the relevant patent barriers end.

Scenario 2: Carved-out labeling before September 2028

A generic could seek approval for indications or dosing information outside the patented use code. This strategy is difficult where the patented titration schedule is part of the standard administration instructions for the approved indication.

A carve-out may reduce exposure to a specific method patent but can create:

• Labeling differences;
• Physician-prescribing constraints;
• Substitution limitations;
• Regulatory review risk; and
• Indirect-infringement arguments based on promotional activity.

Scenario 3: Paragraph IV litigation

A generic may allege that the patent is invalid, unenforceable, or not infringed. The most likely attack points are:

• Obviousness of the titration regimen;
• Written description and enablement for the broad 40-100 mg/day range;
• Indefiniteness of “about” and “stereomerically pure”;
• Anticipation by earlier apremilast clinical or patent disclosures;
• Double patenting over earlier method-of-treatment claims;
• Scope of the disease limitations;
• Whether the accused product label induces administration of the claimed regimen.

Scenario 4: Non-infringing product design

Changing tablet strength, excipients, packaging, or manufacturing site would not necessarily avoid the independent claims. The claims focus on the administered active ingredient and regimen. A design-around would more likely require a different dose-escalation schedule, a different approved indication, or a label that omits the patented use.

How strong is the patent estate for US 10,092,541?

The patent has moderate-to-strong commercial relevance but narrower litigation scope than a composition-of-matter patent.

Strengths

• The 60 mg/day regimen corresponds closely to the FDA-approved Otezla label.
• The claims identify the active enantiomer rather than a broad chemical genus.
• The disease limitations include FDA-approved uses.
• The dependent claims cover common commercial forms, including tablets and free-form apremilast.
• The patent extends beyond the earliest apremilast composition patents.

Vulnerabilities

• The regimen is detailed and may be vulnerable to obviousness arguments based on routine clinical dose escalation.
• The disease list includes several unapproved indications, reducing the immediate Orange Book commercial scope for those uses.
• The broad “about 40 mg/day to about 100 mg/day” language may create construction and enablement disputes.
• Infringement may depend on the generic’s label and on whether physicians administer the precise claimed schedule.
• A generic may seek approval with a carved-out label.

The highest-value claims are claims 2 and 6 for the approved disease areas expressly recited in the claims, together with claims 21 and 22 when the product is a tablet containing free-form, highly enantiopure apremilast.

What patent litigation and settlement issues affect generic launch?

The core litigation question is whether an ANDA applicant’s proposed labeling directs the full five-day titration and 30 mg twice-daily maintenance schedule. If it does, the asserted claims have a direct inducement theory.

Settlement agreements may establish:

• A confidential or public authorized-generic arrangement;
• A licensed launch date before patent expiry;
• A royalty-bearing license;
• Restrictions on indications or promotional materials; or
• A delayed entry date tied to other Otezla patents.

A settlement does not necessarily eliminate all competition. Different ANDA applicants may receive different licensed entry dates, and one applicant’s settlement does not bind an unrelated applicant.

What licensing deals affect ownership of US 10,092,541?

The relevant transaction was the divestiture of Otezla from Celgene to Amgen in 2019. The transaction was structured as an asset sale to resolve antitrust concerns arising from Bristol Myers Squibb’s acquisition of Celgene.[4]

That transaction is better characterized as a transfer of commercial rights and related assets than as a conventional field-of-use license. Amgen became the commercial owner of Otezla and the associated intellectual-property position. Bristol Myers Squibb is therefore not the primary commercial party for Otezla in the United States.

Does US 10,092,541 create biosimilar risk?

No. Apremilast is a small-molecule active pharmaceutical ingredient. The relevant competitors are generic-drug manufacturers filing ANDAs under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

The competitive assessment should focus on:

• Paragraph IV certifications;
• Section viii statements;
• 30-month stays;
• ANDA litigation;
• Generic labeling;
• Patent settlements; and
• Remaining composition, formulation, and solid-state patents.

Biosimilar interchangeability, reference-product exclusivity, and the BPCIA are not applicable.

Key Takeaways

• US 10,092,541 is a regimen patent for apremilast, not a basic composition patent.
• Claims 1-14 require a five-day titration followed by either 40-100 mg/day or 30 mg twice daily.
• Claims 2 and 6 most closely track the approved 60 mg/day regimen for psoriasis and Behcet's disease.
• Dependent claims 15-20 impose enantiomeric purity thresholds from greater than 90% to greater than 99%.
• Claim 21 covers tablet administration; claims 22-24 address free, salt, and solvate forms.
• The expected expiration date is September 24, 2028.
• Generic applicants face ANDA-based Paragraph IV, Section viii, and label-carve-out strategies rather than biosimilar competition.
• A change in excipients or manufacturing process alone is unlikely to avoid the independent claims.
• The most important commercial risk is an approved generic label that reproduces the Otezla titration schedule and 30 mg twice-daily maintenance regimen.
• Amgen is the relevant commercial rights holder following the 2019 Otezla divestiture from Celgene.

FAQs

Can a generic apremilast product avoid US 10,092,541 by using a different tablet strength?

Not necessarily. The independent claims focus on the dose administered, not the tablet’s nominal strength. A different tablet strength may avoid claim 21 in some circumstances but would not necessarily avoid claims 1-14.

Does US 10,092,541 cover psoriatic arthritis?

The supplied claims do not expressly recite psoriatic arthritis. Other Otezla patents or regulatory listings may address that indication, but this patent should be analyzed based on its stated disease limitations.

Can a generic launch for psoriasis before 2028 with a Section viii statement?

Only if the proposed labeling omits the patented method of use and the FDA accepts the carve-out. Because the claimed titration and maintenance schedule tracks the labeled regimen, a complete carve-out may be difficult.

Is the (+) apremilast enantiomer the same active ingredient used in Otezla?

Yes. Otezla contains apremilast, the pharmacologically active (+) enantiomer identified in the patent claims.

Could a salt or solvate design avoid the patent?

Not automatically. Claim 23 covers pharmaceutically acceptable salts, and claim 24 covers pharmaceutically acceptable solvates. A salt or solvate may still fall within the patent if the remaining treatment and dosing limitations are met.

References

1. U.S. Patent and Trademark Office. (2018). U.S. Patent No. 10,092,541, Methods of treating with apremilast. Alexandria, VA: U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (2024). Otezla (apremilast) prescribing information. Silver Spring, MD: U.S. Department of Health and Human Services.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. Silver Spring, MD: U.S. Department of Health and Human Services.

4. Federal Trade Commission. (2019). FTC requires Bristol-Myers Squibb and Celgene to divest psoriasis drug Otezla as a condition of merger. Washington, DC: Federal Trade Commission.

Drugs Protected by US Patent 10,092,541

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amgen Inc	OTEZLA XR	apremilast	TABLET, EXTENDED RELEASE;ORAL	210745-001	Aug 29, 2025		RX	Yes	Yes						TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCET'S DISEASE USING A DOSAGE TITRATION SCHEDULE
Amgen Inc	OTEZLA	apremilast	TABLET;ORAL	205437-001	Mar 21, 2014	AB	RX	Yes	No					Y
Amgen Inc	OTEZLA	apremilast	TABLET;ORAL	205437-002	Mar 21, 2014	AB	RX	Yes	No					Y
Amgen Inc	OTEZLA	apremilast	TABLET;ORAL	205437-003	Mar 21, 2014	AB	RX	Yes	Yes					Y

International Family Members for US Patent 10,092,541

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3188745
World Intellectual Property Organization (WIPO)	2016025686