Details for Patent: 11,446,258

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Which drugs does patent 11,446,258 protect, and when does it expire?

Patent 11,446,258 protects EPIDIOLEX and is included in one NDA.

This patent has thirty-eight patent family members in twenty-one countries.

Summary for Patent: 11,446,258

Title:	Use of cannabinoids in the treatment of epilepsy
Abstract:	The present disclosure relates to the use of cannabidiol (CBD) for the treatment of atonic seizures. In particular the CBD appears particularly effective in reducing atonic seizures in patients suffering with etiologies that include: Lennox-Gastaut Syndrome; Tuberous Sclerosis Complex; Dravet Syndrome; Doose Syndrome; Aicardi syndrome; CDKL5 and Dup15q in comparison to other seizure types. The disclosure further relates to the use of CBD in combination with one or more anti-epileptic drugs (AEDs).
Inventor(s):	Geoffrey Guy, Stephen Wright, Orrin Devinsky
Assignee:	Jazz Pharmaceuticals Research UK Ltd
Application Number:	US17/477,172
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,446,258
Patent Claim Types: see list of patent claims	Use; Formulation;

US Patent 11,446,258: Scope, Claims, Expiration, Orange Book Status, and CBD Patent Landscape

US Patent 11,446,258 protects a dosing regimen for oral cannabidiol at approximately 100 mg/mL in patients with Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex, or Doose syndrome. The core regimen begins at approximately 5 mg/kg/day and increases in approximately 5 mg/kg/day increments to a maximum of approximately 25 mg/kg/day. The patent is directed to Epidiolex-type use, not to CBD as a chemical compound.

The claims are method-of-treatment claims. They cover the combination of patient population, oral administration, formulation concentration, dose-escalation schedule, and, in claim 29, a seizure-reduction outcome.

What does US Patent 11,446,258 protect?

The independent claim requires all of the following:

Required limitation	Scope
Disease	Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex, or Doose syndrome
Treatment	Treatment of seizures
Route	Oral administration
Active ingredient	Cannabidiol, or CBD
Formulation concentration	Approximately 100 mg/mL
Starting dose	Approximately 5 mg/kg/day
Titration	Increase by approximately 5 mg/kg increments
Maximum dose	Approximately 25 mg/kg/day

Claim 1 is therefore narrower than a general claim to CBD for epilepsy. A product or regimen must satisfy the claimed disease, formulation, route, and dosing limitations for literal infringement.

The patent does not claim:

• CBD in all concentrations;
• all epilepsy indications;
• all routes of administration;
• CBD treatment without the specified titration;
• a fixed dose unrelated to the claimed escalation schedule;
• CBD manufacturing or purification;
• a particular excipient system, flavor, container, or packaging configuration.

The patent’s commercial relevance comes from its alignment with the FDA-approved oral CBD product Epidiolex, which contains 100 mg/mL of cannabidiol oral solution.[1]

How do the US 11,446,258 claims differ from one another?

Claims 1 through 12 establish the general regimen and seizure-type variants. Claims 13 through 28 narrow the indication and final dose. Claim 29 adds a therapeutic-response limitation.

Claims	Subject matter
1	Broad four-disease regimen, 5 mg/kg/day starting dose, titration to maximum 25 mg/kg/day
2	Final dose between approximately 10 and 25 mg/kg/day
3	Final dose of approximately 10 mg/kg/day
4	Final dose of approximately 15 mg/kg/day
5	Final dose of approximately 20 mg/kg/day
6	Final dose of approximately 25 mg/kg/day
7-12	Atonic, tonic, clonic, tonic-clonic, absence, or myoclonic seizures
13-16	Lennox-Gastaut syndrome, with escalation to 10 or 20 mg/kg/day
17-20	Dravet syndrome, with escalation to 10 or 20 mg/kg/day
21-23	Tuberous sclerosis complex, with escalation to 25 mg/kg/day
24-28	Doose syndrome, with escalation to 10, 20, or 25 mg/kg/day
29	At least 50% seizure reduction versus baseline

The dependent claims create multiple fallback positions. If a court narrows or invalidates the broad claim, claims directed to a specific syndrome, seizure type, or final dose may remain relevant.

What is the technical scope of the dose-escalation claims?

The dosing architecture tracks the Epidiolex label for several approved indications. The FDA label generally begins treatment at 2.5 mg/kg twice daily, equivalent to 5 mg/kg/day, followed by escalation to 5 mg/kg twice daily, equivalent to 10 mg/kg/day. For Lennox-Gastaut syndrome and Dravet syndrome, the labeled maximum is generally 10 mg/kg twice daily, or 20 mg/kg/day. For tuberous sclerosis complex, the maximum is generally 12.5 mg/kg twice daily, or 25 mg/kg/day.[1]

The patent language uses “about,” which introduces a range of reasonable variation. The exact scope depends on claim construction, specification disclosures, prosecution history, and the evidence presented in litigation. A regimen using 4.8 or 5.2 mg/kg/day might create a closer infringement question than a regimen using 2 or 8 mg/kg/day.

The incremental limitation is important. A patient who receives 5 mg/kg/day and later receives 10 mg/kg/day may fall within the claim even if the prescriber does not use the exact phrase “increase by 5 mg/kg increments.” The legal analysis would focus on the actual administered doses and whether they fall within the construed meaning of the claim.

What does claim 29 add?

Claim 29 requires that administration reduce seizure frequency by at least 50% compared with a baseline period before CBD treatment.

This limitation may narrow the literal scope of the claim, but it creates factual complications:

1. Baseline seizure counts must be established.
2. The relevant observation period must be defined.
3. Seizure diaries and clinical records become important evidence.
4. The reduction must be attributable to the claimed CBD regimen rather than an unrelated antiepileptic change.
5. The claim may be difficult to assess before treatment because the 50% reduction is an outcome limitation.

A generic manufacturer usually cannot control whether an individual patient achieves the claimed response. That does not eliminate risk where the product label, prescribing instructions, marketing, or induced-use evidence encourages the claimed regimen.

What diseases and seizure types are covered?

Lennox-Gastaut syndrome

Claims 13 through 16 focus on Lennox-Gastaut syndrome and escalation to approximately 10 or 20 mg/kg/day. Lennox-Gastaut syndrome is an FDA-approved Epidiolex indication.

Dravet syndrome

Claims 17 through 20 cover Dravet syndrome with escalation to approximately 10 or 20 mg/kg/day. Dravet syndrome is also an FDA-approved Epidiolex indication.

Tuberous sclerosis complex

Claims 21 through 23 cover tuberous sclerosis complex and escalation to approximately 25 mg/kg/day. The FDA approved Epidiolex for seizures associated with TSC in 2020.[2]

Doose syndrome

Claims 24 through 28 cover Doose syndrome. Doose syndrome is included in the patent claims, but it is not one of the principal FDA-approved Epidiolex indications identified in the current US label. This creates a distinction between patent scope and approved labeling.

Seizure types

Claims 7 through 12 cover atonic, tonic, clonic, tonic-clonic, absence, and myoclonic seizures. These dependent claims are not limited to a single syndrome, but they remain subject to the limitations inherited from claim 1 or the relevant dependent claim.

What formulation does US 11,446,258 protect?

The formulation limitation is approximately 100 mg/mL CBD administered orally. This corresponds to the concentration of Epidiolex oral solution.[1]

The patent does not, based on the supplied claims, require a particular:

• solvent;
• carrier oil;
• sweetener;
• flavoring agent;
• preservative;
• cannabinoid purity level;
• plant source;
• container;
• dosing syringe.

That distinction matters. A competing product with the same dose but a materially different CBD concentration may avoid literal infringement of these claims. Conversely, changing excipients may not avoid infringement if the competing formulation remains an oral CBD formulation at approximately 100 mg/mL and is used under the claimed regimen.

What is the relationship between US 11,446,258 and Epidiolex?

Epidiolex is an FDA-approved purified cannabidiol oral solution marketed in the United States by Jazz Pharmaceuticals following Jazz’s acquisition of GW Pharmaceuticals.[3] The product is approved for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex in specified age groups.[1]

The patent claims overlap substantially with the product’s concentration and labeled initiation strategy:

Epidiolex label element	US 11,446,258 claim element
Oral cannabidiol solution	Oral CBD pharmaceutical formulation
100 mg/mL concentration	About 100 mg/mL
Initial total daily dose of 5 mg/kg/day	Starting dose of about 5 mg/kg/day
Escalation to 10 mg/kg/day	Dependent claims 2, 3, 13-20
Escalation to 20 mg/kg/day	Claims 5, 14, 16, 18, and 20
Escalation to 25 mg/kg/day	Claims 6, 22, 23, 25, and 28
Seizure reduction endpoint	Claim 29

This overlap gives the patent potential product-level significance even though the claims are formally directed to treatment methods.

What is the FDA and Orange Book status of US 11,446,258?

Epidiolex is an FDA-approved prescription drug, and FDA lists it in the Orange Book under cannabidiol.[1] Orange Book status must be evaluated by checking the current FDA patent listing, because listed patents, delistings, certifications, and litigation notices can change over time.

A patent can be technically relevant to an approved product without every claim being listed in the Orange Book. The Orange Book listing question is separate from validity, infringement, and enforceability.

For an ANDA applicant, an Orange Book-listed patent may trigger a Paragraph IV certification if the applicant asserts that the patent is invalid, unenforceable, or not infringed. A Paragraph IV notice can prompt patent litigation under the Hatch-Waxman Act and may create a statutory stay of FDA approval, subject to the statutory framework and litigation timing.[4]

When does US Patent 11,446,258 lose exclusivity?

The patent’s enforceable expiration date must be determined from the official patent record, including:

• earliest effective nonprovisional or PCT filing date;
• patent-term adjustment;
• terminal disclaimers;
• patent-term extension;
• regulatory review calculations;
• any disclaimer or correction recorded by the USPTO.

The patent was issued on September 20, 2022. Issuance alone does not determine expiration. The relevant term is generally 20 years from the applicable earliest effective nonprovisional filing date, subject to adjustment under 35 U.S.C. §§ 154 and 156.[5]

The patent’s commercial exclusivity must also be separated from FDA regulatory exclusivity. FDA exclusivity may expire before or after a particular patent, and pediatric exclusivity can add six months to qualifying FDA-listed protections. The current FDA Orange Book and USPTO Patent Center records control the operative dates.[1,6]

How strong is the patent estate around cannabidiol and Epidiolex?

The estate is strongest where a competitor follows the approved product closely. Risk increases when the competing product has:

• 100 mg/mL oral CBD;
• a 5 mg/kg/day starting dose;
• stepwise escalation;
• treatment of LGS, Dravet syndrome, or TSC;
• labeling that recommends the claimed doses;
• promotional materials that encourage the patented regimen.

Risk is lower where the competitor uses:

• a different concentration;
• a nonoral route;
• a materially different titration schedule;
• a disease outside the claimed indications;
• a fixed dose without the claimed escalation;
• a product that is not substituted for Epidiolex through an ANDA.

The claims also face potential validity challenges based on written description, enablement, obviousness, anticipation, claim construction, and whether the claimed regimen represents a patentable distinction over known CBD epilepsy studies and the Epidiolex clinical-development record.

What Paragraph IV challenges and generic-entry risks exist?

A generic CBD applicant would likely evaluate three principal pathways.

Paragraph IV ANDA strategy

An ANDA applicant could argue that:

• the proposed concentration is outside the claim;
• the label does not instruct the claimed titration;
• the proposed indication does not include a claimed syndrome;
• the claims are invalid as obvious or anticipated;
• the patent is unenforceable;
• the product is not intended to induce the claimed use.

The risk is highest if the ANDA label reproduces the Epidiolex dosing instructions.

Section viii carve-out

A Section viii statement could attempt to omit patented method-of-use information from the label. This approach is difficult where the patented regimen is embedded in the approved dosing instructions rather than limited to a separable indication.

At-risk launch

A generic could launch after FDA approval while challenging the patent, subject to litigation exposure. A court could award damages, injunctive relief, or both depending on the facts and applicable law.

Because cannabidiol is a small-molecule drug, generic competition proceeds through the ANDA pathway. Biosimilar analysis under the Public Health Service Act does not apply to Epidiolex.[4]

What manufacturing and intellectual-property barriers remain?

US 11,446,258 does not claim CBD manufacturing. It therefore does not, by itself, block production of CBD active pharmaceutical ingredient or a noninfringing oral formulation.

Commercial barriers may still arise from other patent families covering:

• CBD purification;
• cannabinoid composition;
• pharmaceutical formulations;
• stability;
• dosing devices;
• treatment of additional disorders;
• manufacturing processes;
• analytical specifications.

A freedom-to-operate review must examine the entire family portfolio, not only US 11,446,258. Geographic risk also differs. A US method-of-treatment patent has no direct effect on sales in Europe, Canada, Japan, or other jurisdictions, although corresponding foreign patents may cover similar subject matter.

How does US 11,446,258 compare with competing CBD products?

Product or category	FDA status	Relationship to US 11,446,258
Epidiolex	Approved prescription CBD product	Closest commercial overlap
Generic cannabidiol oral solution	Potential ANDA product	High risk if concentration and titration match
Nonprescription hemp CBD	Not an approved substitute for Epidiolex	Usually different regulatory and labeling position
Synthetic CBD product	Depends on formulation and approval pathway	Chemical source alone may not avoid method claims
Other antiseizure drugs	Approved or investigational products	Generally outside the CBD-specific claims
CBD biosimilar	Not applicable	CBD is a small molecule, not a biologic

What litigation and settlement issues should investors monitor?

The key litigation indicators are:

1. Orange Book listing and any subsequent delisting.
2. Paragraph IV notices from ANDA applicants.
3. Hatch-Waxman complaints filed within 45 days of notice.
4. Patent-term adjustment and terminal-disclaimer records.
5. Claim-construction rulings.
6. Inter partes review petitions at the Patent Trial and Appeal Board.
7. Settlements involving launch dates, authorized generics, or covenant-not-to-sue provisions.
8. FDA approval dates for competing cannabidiol products.

A settlement may establish a commercial entry date without resolving validity. The absence of a public lawsuit does not establish that no Paragraph IV notice has been served, because notice and settlement activity can precede public litigation.

Key Takeaways

• US Patent 11,446,258 is a dosing-regimen patent for oral CBD at approximately 100 mg/mL.
• The core regimen starts at approximately 5 mg/kg/day and escalates in approximately 5 mg/kg/day increments.
• The claims cover LGS, Dravet syndrome, TSC, and Doose syndrome.
• Claims 13 through 28 create syndrome-specific and dose-specific fallback positions.
• Claim 29 requires at least a 50% reduction in seizure frequency compared with baseline.
• The patent closely tracks Epidiolex’s concentration and labeled dosing strategy.
• It does not claim CBD as a molecule, CBD manufacturing, or every CBD formulation.
• Generic risk is greatest for an ANDA product with a 100 mg/mL oral solution and a label reproducing the claimed titration.
• Biosimilar analysis is not applicable because cannabidiol is a small-molecule drug.
• The operative expiration date requires review of USPTO term-adjustment, terminal-disclaimer, and related patent records.
• Patent strength depends heavily on claim construction, prior-art dosing disclosures, prosecution history, and the exact proposed generic label.

FAQs About US Patent 11,446,258

Does US Patent 11,446,258 cover all Epidiolex use?

No. It covers specified oral CBD dosing regimens, concentrations, syndromes, and titration schedules. Use outside those limitations may fall outside the claims.

Can a generic CBD product avoid the patent by using a different concentration?

Potentially. A product materially below or above approximately 100 mg/mL may have a noninfringement position, although other patents or induced-infringement theories may remain relevant.

Is Doose syndrome an FDA-approved Epidiolex indication?

Doose syndrome is included in US Patent 11,446,258, but it is not one of the principal indications identified in the current Epidiolex FDA labeling.

Does a CBD API supplier infringe this patent?

Not necessarily. The claims are directed to methods of treating patients. API manufacture and supply raise different infringement and inducement questions than administering the claimed formulation to a patient.

What is the most exposed generic launch scenario?

The highest-risk scenario is an ANDA applicant proposing a 100 mg/mL oral cannabidiol solution labeled for LGS, Dravet syndrome, or TSC with a 5 mg/kg/day starting dose and stepwise escalation to 10, 20, or 25 mg/kg/day.

References

1. U.S. Food and Drug Administration. (2024). Epidiolex (cannabidiol) oral solution: Prescribing information.
2. U.S. Food and Drug Administration. (2020). FDA approves expanded indication for Epidiolex to treat seizures associated with tuberous sclerosis complex.
3. Jazz Pharmaceuticals plc. (2021). Jazz Pharmaceuticals completes acquisition of GW Pharmaceuticals.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
5. United States Code. (2024). 35 U.S.C. §§ 154 and 156.
6. United States Patent and Trademark Office. (2024). Patent Center: U.S. Patent No. 11,446,258 and related prosecution records.

Drugs Protected by US Patent 11,446,258

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Jazz Pharms Res	EPIDIOLEX	cannabidiol	SOLUTION;ORAL	210365-001	Sep 28, 2018		RX	Yes	Yes	11,446,258					USE FOR THE TREATMENT OF SEIZURES IN PATIENTS WITH LENNOX-GASTAUT SYNDROME
Jazz Pharms Res	EPIDIOLEX	cannabidiol	SOLUTION;ORAL	210365-001	Sep 28, 2018		RX	Yes	Yes	11,446,258					USE FOR THE TREATMENT OF SEIZURES IN PATIENTS WITH DRAVET SYNDROME
Jazz Pharms Res	EPIDIOLEX	cannabidiol	SOLUTION;ORAL	210365-001	Sep 28, 2018		RX	Yes	Yes	11,446,258					USE FOR THE TREATMENT OF SEIZURES IN PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX

International Family Members for US Patent 11,446,258

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2015332212
Australia	2021204353
Australia	2023258400