Details for Patent: 11,998,529

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Which drugs does patent 11,998,529 protect, and when does it expire?

Patent 11,998,529 protects IGALMI and is included in one NDA.

This patent has fourteen patent family members in eleven countries.

Summary for Patent: 11,998,529

Title:	Non-sedating dexmedetomidine treatment regimens
Abstract:	Disclosed herein are methods of administering relatively high doses of dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject, without also inducing significant sedation. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases such as schizophrenia, bipolar illness such as bipolar disorder or mania, dementia, depression, or delirium.
Inventor(s):	Vasukumar KAKUMANU, David Christian HANLEY, Frank Yocca, Chetan Dalpatbhai LATHIA, Lavanya Rajachandran, Robert Risinger
Assignee:	Bioxcel Therapeutics Inc
Application Number:	US18/216,890
Patent Claim Types: see list of patent claims	Use; Formulation;

United States Patent 11,998,529: Dexmedetomidine Oromucosal Agitation Treatment Claims and Patent Landscape

U.S. Patent No. 11,998,529 protects repeat-dose treatment of agitation with an oromucosal dexmedetomidine formulation. The core protected regimen is a specified first dose, a second dose administered at least two hours later, and cardiovascular eligibility criteria, including QTcF below 470 milliseconds. The most commercially important embodiments are a 120 mcg initial dose followed by 60 mcg and a 180 mcg initial dose followed by 90 mcg.

The patent is directed to method-of-use protection for the Igalmi-type product, rather than broad chemical protection for dexmedetomidine. Infringement risk is highest for a competing oromucosal product marketed for acute agitation using the same dose sequence and patient-selection criteria.

What drug and formulation does U.S. Patent 11,998,529 protect?

The patent covers treatment using dexmedetomidine delivered in an oromucosal formulation. Oromucosal administration includes dosage forms placed in the oral cavity for absorption through oral mucosal tissue. Igalmi is a dexmedetomidine sublingual film approved by the FDA for acute treatment of agitation associated with schizophrenia or bipolar disorder in adults.[1]

The claims do not cover every use of dexmedetomidine. They require:

• A human subject;
• Agitation;
• An oromucosal dexmedetomidine formulation;
• A specified initial dose;
• A second dose after at least two hours;
• A specified second dose; and
• A QTcF below 470 milliseconds in the principal claims.

The claimed dosage strengths are expressed as micrograms of dexmedetomidine, not merely film weight or total formulation weight.

What are the key claim limitations in Patent 11,998,529?

Claim 1 is the broadest independent claim supplied. It covers several dose combinations:

Initial dose	Permitted second dose under claim 1
60 mcg	40, 60, 80 or 90 mcg
80 mcg	40, 60, 80 or 90 mcg
90 mcg	40, 60, 80 or 90 mcg
120 mcg	40, 60, 80 or 90 mcg
180 mcg	40, 60, 80 or 90 mcg

The second dose must be administered after at least two hours. Claim 1 also requires persistent agitation and QTcF below 470 milliseconds.

Claims 2 through 9 narrow the dose selections. Claims 10 and 11 identify the two most commercially significant fixed regimens:

• 120 mcg followed by 60 mcg;
• 180 mcg followed by 90 mcg.

Claims 15 and 17 independently recite those same fixed-dose regimens. This creates multiple claim paths covering the principal approved Igalmi dosing instructions.

How do the independent claims differ from the dependent claims?

Claims 1, 15 and 17 are the principal enforcement claims.

Claim 1

Claim 1 has the broadest dose coverage but includes multiple clinical limitations. A potential infringement analysis would ask whether the accused product and prescribing instructions satisfy all of the following:

1. Dexmedetomidine is delivered by an oromucosal formulation.
2. The patient is being treated for agitation.
3. The initial dose falls within the five listed strengths.
4. The second dose is given no earlier than two hours after the first.
5. The second dose falls within the four listed strengths.
6. The agitation is persistent.
7. QTcF is below 470 milliseconds.

Claims 15 and 17

Claims 15 and 17 are narrower but easier to apply when the accused regimen follows approved dosing:

• Claim 15: 120 mcg initially, followed by 60 mcg after at least two hours.
• Claim 17: 180 mcg initially, followed by 90 mcg after at least two hours.

These claims do not require the additional blood-pressure, heart-rate or Percent of Expected Change, or PEC, limitation found in claims 12 and 13.

Claims 12 and 13

Claim 12 limits repeat dosing to a patient with a change in PEC score of 40% or less after the initial dose. Claim 13 requires systolic/diastolic blood pressure above 90/60 and heart rate above 60 beats per minute.

These limitations may reduce infringement exposure because they require clinical or prescribing records showing the specified response and vital signs. They also create potential written-description, enablement and indefiniteness issues depending on the patent specification and prosecution record.

What dose regimens are most commercially important?

The 120/60 mcg and 180/90 mcg regimens are the central commercial embodiments.

Regimen	Clinical role	Patent coverage
120 mcg, then 60 mcg	Lower approved initial dose, generally associated with less severe agitation	Claims 10 and 15
180 mcg, then 90 mcg	Higher approved initial dose, generally associated with more severe agitation	Claims 11 and 17
60, 80 or 90 mcg initial dose	Broader claimed regimen set	Claims 1-3
40, 60, 80 or 90 mcg repeat dose	Broader claimed repeat-dose set	Claims 1-9

The patent reaches beyond the principal FDA-approved dose pairs by covering additional combinations. That broader coverage could matter if a competitor develops a modified titration protocol rather than copying the labeled 120/60 or 180/90 regimen.

What formulation patents protect dexmedetomidine oromucosal products?

Patent 11,998,529 is primarily a treatment-regimen patent. It does not, based on the supplied claims, require a particular film polymer, backing layer, mucoadhesive, dissolution profile, manufacturing process or excipient system.

The relevant patent estate may therefore contain separate families directed to:

• Dexmedetomidine oral or sublingual films;
• Film composition and excipient selection;
• Drug loading and content uniformity;
• Oromucosal dissolution and absorption;
• Manufacturing processes;
• Specific dosing regimens;
• Safety screening based on QTcF, blood pressure or heart rate;
• Treatment of agitation associated with schizophrenia or bipolar disorder.

A competitor may avoid the claims of Patent 11,998,529 by using a non-oromucosal route, such as intravenous or intramuscular administration. That design-around would not necessarily avoid separate formulation or method-of-use patents covering the same product platform.

What is the FDA regulatory status of the covered product?

The FDA approved Igalmi, dexmedetomidine hydrochloride sublingual film, in April 2022 for the acute treatment of agitation associated with schizophrenia or bipolar disorder in adults.[1] The approval established a product-specific regulatory framework for sublingual dexmedetomidine.

The FDA label identifies dose selection based on the severity of agitation and permits a second dose after the initial dose when clinically appropriate. The label also contains cardiovascular warnings and restrictions relevant to the QTcF, blood-pressure and heart-rate limitations in the patent claims.[1]

The product is a small-molecule drug. Biosimilar approval is therefore not the applicable competitive pathway. A competing product would generally proceed through an abbreviated new drug application, a 505(b)(2) application, or a full NDA, depending on formulation, clinical evidence and reference-product reliance.

What is the Orange Book status of Patent 11,998,529?

Orange Book listing must be assessed separately from patent issuance. A patent may be enforceable without being listed in the Orange Book, and an Orange Book listing does not establish ultimate validity or infringement.

For Igalmi, the relevant Orange Book analysis includes:

• Whether Patent 11,998,529 is listed against the approved NDA;
• Whether earlier Igalmi patents remain listed;
• The listed claims or use codes;
• Any pediatric exclusivity or patent-term adjustment;
• Whether an ANDA applicant must address the patent through Paragraph IV certification.

The supplied claims alone do not establish the patent’s current Orange Book listing status or any applicable use code. The listing question should be determined from the FDA Orange Book entry for the Igalmi NDA and its monthly supplements.[2]

When does Patent 11,998,529 lose exclusivity?

The ordinary U.S. patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and any patent-term extension.[3]

The issue date, May 28, 2024, does not determine the expiration date. For this patent family, the controlling term must be calculated from the earliest effective filing date shown in the continuity data, then adjusted for any USPTO patent-term adjustment. A terminal disclaimer could cause Patent 11,998,529 to expire with an earlier related patent.

FDA regulatory exclusivity is separate from patent exclusivity. Igalmi received approval in 2022, but the principal market barrier for a competing dexmedetomidine sublingual film is likely to be the combined effect of FDA exclusivity, Orange Book-listed patents and formulation-development requirements rather than this patent alone.

What Paragraph IV challenges could target this patent?

An ANDA applicant seeking approval for a dexmedetomidine sublingual film could submit a Paragraph IV certification if Patent 11,998,529 is listed in the Orange Book. Potential positions would include:

Challenge theory	Potential argument
Noninfringement	The proposed label does not instruct the claimed second dose, timing, QTcF threshold or persistent-agitation condition
Invalidity for anticipation	A prior clinical protocol disclosed the same dose sequence and patient criteria
Obviousness	Prior dexmedetomidine dosing, agitation-treatment data and safety monitoring made the regimen predictable
Written description	The specification did not adequately support the full combination of doses and physiological criteria
Enablement	The patent does not enable the full scope without undue experimentation
Indefiniteness	Terms such as “persistent” agitation or “change in PEC score” lack objective boundaries
Divided-performance defense	No single actor performs or controls all claimed clinical steps

The strongest noninfringement strategy would usually involve a different route of administration, a different labeled indication, omission of the repeat-dose instruction, or a dosing interval shorter than two hours. A generic applicant cannot rely solely on physician noncompliance if the proposed label itself encourages the patented method.

How strong is the patent estate for Igalmi?

Patent 11,998,529 is commercially meaningful but narrow compared with a composition-of-matter patent.

Factor	Assessment
Chemical scope	Weak or absent; the claims do not broadly claim dexmedetomidine as a molecule
Formulation scope	Limited in the supplied claims; “oromucosal formulation” is broad but no specific excipient system is required
Method-of-use scope	Strong for the recited acute-agitation regimens
Dose coverage	Broad across listed initial and repeat doses
Safety-screening coverage	Meaningful through QTcF, vital-sign and PEC limitations
Design-around potential	Moderate; route, indication, timing and labeling changes may reduce risk
Litigation leverage	Highest if the competing product copies the approved 120/60 or 180/90 instructions
Biosimilar relevance	None; dexmedetomidine is a small molecule

The patent’s strongest feature is claim redundancy. The 120/60 and 180/90 regimens are covered by both broad combination claims and fixed-dose independent claims. A successful challenge to one claim does not automatically eliminate the other claim paths.

Which companies are most likely to challenge the patent?

The likely challengers are manufacturers developing:

• A sublingual dexmedetomidine film;
• A buccal dexmedetomidine film;
• An orally dissolving dexmedetomidine dosage form;
• A 505(b)(2) product relying on Igalmi safety and efficacy data;
• An ANDA product with an identical or substantially identical labeled dose sequence.

Generic injectable dexmedetomidine manufacturers are not direct challengers unless they develop an oromucosal product. Injectable Precedex or generic dexmedetomidine products do not practice the oromucosal limitation merely because they contain the same active ingredient.

No conclusion about a specific Paragraph IV notice, ANDA filing, patent litigation case or settlement agreement follows from the claims supplied. Patent issuance itself does not establish that a challenge has been filed or that the patent has been asserted.

What generic launch scenarios exist?

Scenario 1: Identical sublingual regimen

A competitor copies the 120/60 and 180/90 instructions. This creates the highest infringement risk under claims 15 and 17, assuming the competing formulation is oromucosal and the label addresses agitation.

Scenario 2: Different repeat-dose timing

A label permits a second dose only before two hours or does not authorize a second dose. This may avoid the literal timing limitation, although other patents or induced-infringement theories could remain relevant.

Scenario 3: Different route

A buccal, oral-swallowed, intranasal or injectable formulation may avoid the scope of “oromucosal formulation,” depending on claim construction and the product’s absorption route.

Scenario 4: Different indication

A dexmedetomidine oromucosal product for procedural sedation, insomnia or another indication may avoid the agitation limitation. The product could still face formulation patents.

Scenario 5: Label carve-out

An applicant may attempt to omit the patented agitation-use instructions through a section viii statement if the patent is listed with an appropriate method-of-use code. That strategy depends on the actual Orange Book listing and whether the remaining label still necessarily encourages the claimed method.

What patent litigation or settlement issues matter?

The principal litigation questions would be:

1. Whether “oromucosal formulation” includes the accused dosage form;
2. Whether a product label induces administration of the claimed second dose;
3. Whether QTcF below 470 milliseconds is a patient-selection limitation or an inherent property;
4. Whether “persistent agitation” is sufficiently definite;
5. Whether the full dose matrix is supported by the specification;
6. Whether prior clinical studies disclosed the claimed repeat-dose regimen;
7. Whether any related patent has a terminal disclaimer.

A settlement could include a licensed launch date, a permitted dosage-form design, a covenant not to sue, or an authorized generic arrangement. The patent claims alone do not disclose settlement terms or a litigation resolution.

How does Patent 11,998,529 compare with generic dexmedetomidine patents?

Issue	Patent 11,998,529	Conventional dexmedetomidine patent
Main subject	Repeat-dose treatment of agitation	Compound, salt, formulation or manufacturing process
Product dependency	High; requires an oromucosal product	Variable
Clinical dependency	High; requires specified dosing and patient criteria	Usually lower
Design-around	Route, timing, indication or label	Chemical or formulation substitution
Relevance to injectable dexmedetomidine	Low	Potentially high
Relevance to Igalmi substitutes	High	High if formulation claims overlap

Key Takeaways

• U.S. Patent 11,998,529 is a method-of-use patent covering repeat-dose oromucosal dexmedetomidine for agitation.
• The most important claimed regimens are 120 mcg followed by 60 mcg and 180 mcg followed by 90 mcg.
• Claim 1 covers a broader dose matrix but requires persistent agitation, a two-hour minimum interval and QTcF below 470 milliseconds.
• Claims 15 and 17 provide direct protection for the two principal fixed-dose regimens.
• Claims 12 through 14 and 16 and 18 add clinical-selection limitations involving PEC response, blood pressure, heart rate and QTcF.
• The patent does not broadly monopolize dexmedetomidine, injectable dexmedetomidine or every oral formulation.
• Biosimilar competition is not applicable because dexmedetomidine is a small-molecule drug.
• A competing sublingual or buccal product copying the Igalmi dosing instructions faces the highest infringement exposure.
• Orange Book listing, terminal disclaimers, patent-term adjustment and related formulation patents must be evaluated with the complete patent family and FDA records.

FAQs About U.S. Patent 11,998,529

Does Patent 11,998,529 cover Igalmi itself?

It covers methods of using an oromucosal dexmedetomidine formulation for agitation. It does not, based on the supplied claims, broadly claim every physical embodiment of Igalmi or dexmedetomidine.

Can injectable dexmedetomidine infringe this patent?

Injectable dexmedetomidine generally would not satisfy the oromucosal-formulation limitation. Separate patents or regulatory exclusivities could still apply.

Is the 120 mcg plus 60 mcg regimen specifically claimed?

Yes. Claim 10 and independent claim 15 specifically recite an initial 120 mcg dose followed by a 60 mcg dose after at least two hours.

Is the 180 mcg plus 90 mcg regimen specifically claimed?

Yes. Claim 11 and independent claim 17 specifically recite an initial 180 mcg dose followed by a 90 mcg dose after at least two hours.

Does the patent cover treatment when QTcF is 470 milliseconds or higher?

No. The supplied principal claims require QTcF below 470 milliseconds. Claims 14, 16 and 18 narrow the threshold to below 450 milliseconds.

References

1. U.S. Food and Drug Administration. (2022). Igalmi (dexmedetomidine) sublingual film prescribing information.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. United States Patent and Trademark Office. (2024). U.S. Patent No. 11,998,529.
4. United States Code. (2024). 35 U.S.C. §§ 154, 271 and 282.
5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications under the Hatch-Waxman Amendments.

Drugs Protected by US Patent 11,998,529

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bioxcel	IGALMI	dexmedetomidine hydrochloride	FILM;BUCCAL, SUBLINGUAL	215390-001	Apr 5, 2022		RX	Yes	Yes	11,998,529					ACUTE TREATMENT OF AGITATION ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR I OR II DISORDER BY SUBLINGUAL OR BUCCAL ADMINISTRATION
Bioxcel	IGALMI	dexmedetomidine hydrochloride	FILM;BUCCAL, SUBLINGUAL	215390-002	Apr 5, 2022		RX	Yes	No	11,998,529					ACUTE TREATMENT OF AGITATION ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR I OR II DISORDER BY SUBLINGUAL OR BUCCAL ADMINISTRATION

International Family Members for US Patent 11,998,529

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2020316013
Brazil	112022000992
Canada	3145388
China	114375191