Details for Patent: 10,188,652

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Which drugs does patent 10,188,652 protect, and when does it expire?

Patent 10,188,652 protects DAYVIGO and is included in one NDA.

This patent has eighteen patent family members in thirteen countries.

Summary for Patent: 10,188,652

Title:	Compositions and methods for treating insomnia
Abstract:	In the present invention, compound such as (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl) cyclopropanecarboxamide have been found to be potent orexin receptor antagonists, and may be useful in the treatment of sleep disorders such as insomnia, as well as for other therapeutic uses.
Inventor(s):	Margaret Moline, Gina PASTINO, Yurie AKIMOTO, Yasuhiro Zaima, Nobuya Suzuki, Nobuo Yoshida
Assignee:	Eisai R&D Management Co Ltd
Application Number:	US15/519,676
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

United States Patent 10,188,652: Lemborexant Claims, Scope, Expiration and Patent Landscape

U.S. Patent No. 10,188,652 covers two related aspects of lemborexant, marketed by Eisai as Dayvigo: pharmacokinetically defined once-daily insomnia treatment and immediate-release oral dosage forms containing lemborexant, lactose and low-substituted hydroxypropyl cellulose. The patent issued January 29, 2019, and has a projected term extending into February 2035, subject to the official patent-term calculation and any applicable adjustment.

The patent is important because its claims do not rely only on the chemical identity of lemborexant. They also require specific dose levels, human-exposure parameters, late-time plasma concentrations or dissolution performance. Those limitations create potential design-around routes, but they also make infringement dependent on clinical, pharmacokinetic and product-testing evidence.

What drug and active ingredient does U.S. Patent 10,188,652 cover?

The claimed compound is lemborexant, the dual orexin receptor antagonist in Dayvigo.

Its chemical name is:

(1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide.

Lemborexant has two relevant pharmacological properties:

• Antagonism of orexin OX1 and OX2 receptors.
• Central nervous system activity used for treatment of insomnia characterized by difficulty with sleep onset or sleep maintenance.

The FDA approved Dayvigo in December 2019 in 5 mg and 10 mg tablets for adults with insomnia characterized by difficulties with sleep onset or sleep maintenance.[1]

Eisai is the principal patent owner and commercial sponsor associated with the lemborexant franchise. The patent estate includes earlier composition-of-matter protection and later protection directed to dosage forms, pharmacokinetics, treatment regimens and related pharmaceutical compositions.

What are the independent claims in U.S. Patent 10,188,652?

The patent has two substantive independent claims.

Claim	Category	Core limitation
1	Method of treatment	Oral treatment of insomnia with 2.5 mg to 10 mg of lemborexant once daily, achieving a specified mean Cmax per mg
14	Oral dosage form	Lemborexant, lactose and low-substituted hydroxypropyl cellulose, with at least 85% dissolution within 30 minutes under specified conditions

Claim 1 is a pharmacokinetic treatment claim. Claim 14 is a product and dissolution claim. Claims 2 through 13 depend from claim 1. Claim 15 depends from claim 14.

How does claim 1 define the protected insomnia treatment?

Claim 1 requires all of the following:

1. Treatment of insomnia.
2. Oral administration.
3. A dosage form containing a therapeutically effective amount of lemborexant.
4. A single daily dose of approximately 2.5 mg to approximately 10 mg.
5. A mean Cmax of approximately 3.0 ng/mL to approximately 7.2 ng/mL for each 1 mg of lemborexant after administration to human subjects.

The Cmax requirement is central. It means that a product may not fall within claim 1 merely because it contains lemborexant in a 2.5 mg to 10 mg dose. The accused regimen must also produce the claimed mean exposure per milligram.

At the endpoints, the claim corresponds approximately to the following total-dose Cmax ranges:

Dose	Lower calculated Cmax	Upper calculated Cmax
2.5 mg	7.5 ng/mL	18.0 ng/mL
5 mg	15.0 ng/mL	36.0 ng/mL
10 mg	30.0 ng/mL	72.0 ng/mL

The claim uses “about,” so ordinary claim-construction principles will determine the permissible variation. The dependent claims provide more specific reference values.

What pharmacokinetic parameters are protected by claims 2 through 13?

Claims 2 through 13 create multiple overlapping exposure limitations.

Claim	Dose or parameter	Claimed reference
2	5 mg once daily	Mean Cmax within 80%-125% of 23 ng/mL
3	10 mg once daily	Mean Cmax within 80%-125% of 36 ng/mL
4	Any covered dose	AUC(0-24) of 15.9-23.8 ng·hr/mL per mg
5	5 mg once daily	AUC(0-24) within 80%-125% of 95 ng·hr/mL
6	10 mg once daily	AUC(0-24) within 80%-125% of 159 ng·hr/mL
7	Any covered dose	AUC(0-t) of 19.1-51.1 ng·hr/mL per mg
8	5 mg once daily	AUC(0-t) within 80%-125% of 128 ng·hr/mL
9	10 mg once daily	AUC(0-t) within 80%-125% of 284 ng·hr/mL
10	Any covered dose	AUC(0-inf) of 19.8-53.1 ng·hr/mL per mg
11	5 mg once daily	AUC(0-inf) within 80%-125% of 149 ng·hr/mL
12	10 mg once daily	AUC(0-inf) within 80%-125% of 311 ng·hr/mL
13	Any covered dose	Mean plasma concentration of about 20 ng/mL or less at 8-10 hours

The 80%-125% language is especially significant. It creates a bioequivalence-style range around the stated reference value:

Parameter	5 mg reference	Approximate 80%-125% range	10 mg reference	Approximate 80%-125% range
Cmax	23 ng/mL	18.4-28.75 ng/mL	36 ng/mL	28.8-45 ng/mL
AUC(0-24)	95 ng·hr/mL	76-118.75	159 ng·hr/mL	127.2-198.75
AUC(0-t)	128 ng·hr/mL	102.4-160	284 ng·hr/mL	227.2-355
AUC(0-inf)	149 ng·hr/mL	119.2-186.25	311 ng·hr/mL	248.8-388.75

These values are mean pharmacokinetic outcomes, not necessarily limits applicable to every individual subject. An infringement analysis would likely examine the design and results of a relevant human pharmacokinetic study, including population, fed or fasted state, sampling schedule and statistical treatment.

How does claim 13 expand the scope?

Claim 13 addresses residual exposure later in the dosing interval. It requires a mean plasma lemborexant concentration of approximately 20 ng/mL or less at 8 to 10 hours after administration.

This limitation may be relevant to next-morning impairment and safety. It also creates a separate enforcement theory. A product could satisfy a Cmax or AUC limitation while avoiding claim 13 if its late-time concentration exceeds the stated level. Conversely, a formulation could potentially satisfy claim 13 without falling within every AUC limitation.

What formulation is protected by claim 14?

Claim 14 covers an oral dosage form containing:

• Lemborexant;
• Lactose; and
• Low-substituted hydroxypropyl cellulose, often abbreviated L-HPC.

The dosage must contain a single daily dose of approximately 2.5 mg to 10 mg and meet a dissolution requirement:

• At least 85% dissolution within 30 minutes;
• 0.1 mol/L hydrochloric acid;
• 0.5% polysorbate 80;
• 900 mL medium;
• 37 ± 0.5°C;
• USP Apparatus 2;
• 75 rpm;
• Immediate-release procedure under JP16 or USP <711>.

Claim 15 narrows the dissolution requirement by removing polysorbate 80 and requiring:

• At least 85% dissolution within 15 minutes;
• 0.1 mol/L hydrochloric acid;
• 900 mL medium;
• 37 ± 0.5°C;
• 50 rpm;
• USP Apparatus 2.

The excipient limitations matter. A tablet containing lemborexant but using microcrystalline cellulose, crospovidone or another disintegrant instead of L-HPC may avoid literal infringement of claim 14. The analysis would still require review of the full formulation and any doctrine-of-equivalents theory.

How strong is the patent estate for lemborexant?

The lemborexant estate has several layers:

Protection layer	Strategic function	Principal risk
Composition of matter	Covers lemborexant as a chemical entity	Usually the strongest barrier to generic substitution
Method of treatment	Covers insomnia treatment at defined dose and exposure levels	Requires proof of the claimed clinical regimen and pharmacokinetics
Formulation	Covers lactose/L-HPC oral dosage forms	Can be avoided through excipient or manufacturing changes
Dissolution performance	Protects rapid immediate-release release behavior	Requires standardized product testing
Regulatory exclusivity	Delays ANDA approval independently of patents	Expires separately from patent rights

The composition-of-matter patent is generally the principal barrier for any generic lemborexant product. Patent 10,188,652 is more targeted. Its method claims may reach a generic product that uses the same 5 mg or 10 mg dose and produces comparable exposure. Its formulation claims may reach products using the same excipient architecture and rapid dissolution profile.

The patent is less resistant to a generic that:

• Uses a different excipient system;
• Produces exposure outside the claimed pharmacokinetic ranges;
• Uses a different dosage strength or dosing schedule;
• Does not meet the claimed dissolution conditions; or
• Challenges the claims as anticipated, obvious, indefinite or insufficiently enabled.

When does U.S. Patent 10,188,652 expire?

The patent issued on January 29, 2019. Public Orange Book and patent-term records associate the patent with a February 2035 expiration period. The projected term is approximately 20 years from the relevant nonprovisional filing or priority framework, subject to patent-term adjustment and any terminal disclaimer.

The practical exclusivity timeline is:

Event	Date or period
Patent issued	January 29, 2019
Dayvigo FDA approval	December 20, 2019
Five-year NCE exclusivity	Through December 20, 2024
Potential pediatric exclusivity	May extend FDA protection by six months if awarded
Projected patent expiration	February 2035 period
Earliest ordinary generic entry	Dependent on Orange Book patents, Paragraph IV outcomes and settlement terms

Patent expiration and FDA approval do not establish the same date. A patent can expire after regulatory exclusivity, while an ANDA applicant may challenge the patent before expiration.

What is the Orange Book status of lemborexant and Dayvigo?

Dayvigo is an FDA-approved small-molecule drug, so generic applicants would normally use the ANDA pathway rather than the biosimilar pathway. FDA Orange Book listings identify patents that the NDA holder has submitted as claiming the drug, its approved use or an approved method of use.[2]

The relevant Orange Book questions are:

• Whether U.S. Patent 10,188,652 remains listed;
• Whether the listing covers the 5 mg and 10 mg tablets;
• Whether any use code limits the scope of a method-of-use listing;
• Whether later Eisai patents have been added;
• Whether pediatric exclusivity has altered the effective regulatory date.

Because lemborexant is a small molecule, biosimilar analysis is not applicable. Competitive entry will occur through ANDA litigation, a Paragraph IV certification or a post-expiration Paragraph III certification.

Which companies are likely to challenge Dayvigo exclusivity?

No public information supplied with the claim set establishes a filed Paragraph IV challenge or active patent litigation against U.S. Patent 10,188,652. The commercial challenger would most likely be a generic pharmaceutical company filing an ANDA for lemborexant tablets.

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

1. Anticipation by earlier lemborexant clinical or formulation disclosures.
2. Obviousness based on known orexin antagonists, dose-ranging studies and conventional tablet formulation.
3. Indefiniteness of “about,” “therapeutically effective amount,” “mean,” or the 8-to-10-hour sampling period.
4. Lack of written description for the claimed pharmacokinetic ranges.
5. Lack of enablement across the full 2.5 mg to 10 mg dose range.
6. Noninfringement based on different pharmacokinetics or excipients.
7. Failure of the claimed formulation to distinguish over prior-art immediate-release compositions.

The patent holder would likely rely on clinical data, dose-response evidence and formulation-development records to show that the PK and dissolution limits reflect a technically meaningful product rather than routine optimization.

What patent litigation or settlement agreements affect lemborexant?

The supplied information does not establish a public district-court complaint, Paragraph IV notice, final judgment or settlement agreement specifically directed to U.S. Patent 10,188,652.

A settlement involving this patent could control generic launch before the projected February 2035 expiration. Key terms would include:

• Authorized generic rights;
• Earliest launch date;
• Patent-by-patent release dates;
• Allocation of damages or litigation costs;
• Whether the generic can launch after invalidation of another patent;
• Restrictions on formulation or indication labeling.

The absence of a confirmed public challenge should not be treated as evidence that the patent is unchallengeable. The commercial value of a Paragraph IV case depends heavily on the earlier composition-of-matter patent and the number of listed patents remaining when an ANDA is filed.

What generic launch scenarios exist for lemborexant?

Scenario 1: No early challenge

A generic applicant waits for patent and regulatory barriers to expire. Entry would occur near the end of the listed patent term, subject to any pediatric exclusivity and patent-term adjustment.

Scenario 2: Paragraph IV challenge to the composition patent

This is the highest-value litigation route. Success could permit earlier entry across multiple dosage forms because the generic would not need to rely only on a formulation or method-of-use attack.

Scenario 3: Formulation design-around

A generic could use a different binder or disintegrant system and seek to avoid claims 14 and 15. That strategy would not resolve a valid composition-of-matter patent.

Scenario 4: Carve-out of an insomnia indication

A skinny-label approach could address method-of-use patents, but it would not avoid a composition patent covering lemborexant itself. It would also require careful analysis of labeling, promotional conduct and inducement risk.

How does this patent compare with the broader lemborexant estate?

Patent 10,188,652 is narrower than a chemical composition patent but more commercially specific than a general method-of-treatment patent.

Patent type	Breadth	Relevance to generic Dayvigo
Lemborexant composition patent	Broadest	Direct barrier to any lemborexant product
PK-defined method patent	Intermediate	Strong where the generic matches approved dose and exposure
Lactose/L-HPC formulation patent	Narrower	Vulnerable to excipient and process design-arounds
Dissolution claim	Narrow and test-dependent	Requires product testing under exact conditions
Regulatory exclusivity	Time-limited	Blocks approval regardless of patent validity

The most defensible claims are likely those supported by reproducible clinical and formulation data. The most attackable limitations are the numerical PK boundaries, because they may raise questions about statistical variability, sampling conditions and whether the boundaries are inherent in ordinary administration of lemborexant.

What is the commercial exposure from this patent?

Dayvigo’s exposure to patent erosion depends on product revenue, dose mix, payer adoption and the timing of generic entry. A 5 mg/10 mg tablet product has a straightforward ANDA pathway, so a successful challenge could affect the primary commercial presentations simultaneously.

Patent 10,188,652 is not, by itself, the entire revenue barrier. Its commercial effect is cumulative with:

• The chemical composition patent;
• Any later formulation or solid-form patents;
• FDA exclusivity;
• Use-code protections;
• Manufacturing know-how;
• Patent litigation outcomes.

For valuation, the relevant variable is not merely the February 2035 expiry date. It is the probability-weighted date at which an ANDA applicant can obtain approval and launch without violating a surviving composition patent.

Key Takeaways

• U.S. Patent 10,188,652 covers lemborexant treatment and specified immediate-release dosage forms.
• Claims 1 through 13 require dose and human pharmacokinetic outcomes, including Cmax, AUC and late-time plasma concentration limits.
• Claims 14 and 15 require lactose, L-HPC and rapid dissolution under detailed USP or Japanese Pharmacopoeia test conditions.
• The patent issued January 29, 2019, with a projected expiration in the February 2035 period.
• The strongest commercial barrier remains the broader lemborexant composition-of-matter estate.
• The formulation claims have identifiable design-around paths, while the PK claims require detailed human-subject and product-performance analysis.
• Lemborexant is a small molecule. Generic entry would use the ANDA pathway, not a biosimilar pathway.
• No confirmed Paragraph IV challenge, final judgment or settlement agreement directed specifically to Patent 10,188,652 is established by the supplied record.

FAQs About U.S. Patent 10,188,652 and Lemborexant

Does Patent 10,188,652 cover all lemborexant products?

No. The patent covers specified once-daily insomnia regimens and oral dosage forms meeting particular excipient and dissolution requirements. Broader coverage may arise from separate lemborexant composition patents.

Can a generic avoid the patent by using a different tablet excipient?

Potentially, but only for claims 14 and 15. A different excipient system does not avoid a valid composition-of-matter patent or a method claim that is infringed through the approved dosing regimen.

Are the 80%-125% PK ranges conventional bioequivalence limits?

They resemble bioequivalence limits, but their legal effect depends on the claim language and construction. The ranges define numerical boundaries around the stated mean Cmax and AUC reference values.

Does a Paragraph III ANDA certification permit immediate launch?

No. A Paragraph III certification acknowledges that the listed patent remains valid and enforceable until its stated expiration. Approval and launch generally remain subject to the patent term and any regulatory exclusivity.

Is lemborexant subject to biosimilar competition?

No. Lemborexant is a chemically synthesized small molecule. Competition would arise through generic-drug approval under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

References

1. U.S. Food and Drug Administration. (2019). Dayvigo (lemborexant) prescribing information. FDA.

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

3. United States Patent and Trademark Office. (2019). U.S. Patent No. 10,188,652: Pharmaceutical composition and method of treating insomnia. USPTO.

4. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation. USPTO.

5. U.S. Food and Drug Administration. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j). FDA.

Drugs Protected by US Patent 10,188,652

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Eisai Inc	DAYVIGO	lemborexant	TABLET;ORAL	212028-001	Apr 7, 2020		RX	Yes	No			Y			TREATMENT OF ADULT PATIENTS WITH INSOMNIA, CHARACTERIZED BY DIFFICULTIES WITH SLEEP ONSET AND/OR SLEEP MAINTENANCE
Eisai Inc	DAYVIGO	lemborexant	TABLET;ORAL	212028-002	Apr 7, 2020		RX	Yes	Yes			Y			TREATMENT OF ADULT PATIENTS WITH INSOMNIA, CHARACTERIZED BY DIFFICULTIES WITH SLEEP ONSET AND/OR SLEEP MAINTENANCE

Foreign Priority and PCT Information for Patent: 10,188,652

PCT Information
PCT Filed	October 21, 2015	PCT Application Number:	PCT/JP2015/080304
PCT Publication Date:	April 28, 2016	PCT Publication Number:	WO2016/063995

International Family Members for US Patent 10,188,652

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2015336463
Brazil	112017007063
Canada	2964504
China	107810006
European Patent Office	3209298
Spain	2843952
Israel	251759