Details for Patent: 9,592,207

Which drugs does patent 9,592,207 protect, and when does it expire?

Patent 9,592,207 protects SPRAVATO and is included in one NDA.

This patent has six patent family members in six countries.

Summary for Patent: 9,592,207

Title:	Intranasal administration of ketamine to treat depression
Abstract:	Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (>2 years).
Inventor(s):	Dennis S. Charney, Sanjay J. Mathew, Husseini K. Manji, Carlos A. Zarate, John H. Krystal
Assignee:	Yale University , Icahn School of Medicine at Mount Sinai , US Department of Veterans Affairs , US Department of Health and Human Services
Application Number:	US14/306,382
Patent Claim Types: see list of patent claims	Use;

US Patent 9,592,207 is a broad method-of-treatment patent covering intranasal ketamine for depression that has failed at least two adequate antidepressant treatments. Its principal commercial relevance is Spravato, the esketamine nasal spray marketed by Janssen Pharmaceuticals. The patent does not claim a particular nasal device, excipient system, concentration, or manufacturing process. It claims the clinical use, patient population, route, dosing concepts, and rapid antidepressant response. The patent was granted on March 14, 2017, and its reported expiration date is June 30, 2027. FDA-listed exclusivity for esketamine has expired, but the patent remains the primary Orange Book barrier associated with the core treatment method. [1-4]

US Patent 9,592,207 Ketamine Depression Treatment Patent Analysis

What does US Patent 9,592,207 protect?

US Patent 9,592,207 protects methods for treating depression by intranasally administering ketamine to a patient whose depression has not responded to at least two adequate antidepressant treatments. The patent is directed to therapeutic use rather than to ketamine as a chemical compound.

The independent claims are claims 1 and 15:

Claim	Core limitation
1	Intranasal ketamine for depression after failure of at least two adequate antidepressant treatments
15	Intranasal ketamine after failure of at least two adequate antidepressant treatments

Claim 1 contains the broader dosing and treatment framework. Claim 15 is independently drafted and omits several limitations that appear in dependent claims. A product or treatment method could therefore fall within claim 15 even if it does not satisfy the narrower dose, rapid-response, combination-treatment, or major-depressive-disorder limitations in claims 2 through 14.

The patent's central protected combination is:

1. A patient with depression.
2. Failure to respond to at least two adequate antidepressant treatments.
3. Intranasal administration.
4. Ketamine.
5. A dose effective to alleviate depression.

The claims do not require:

• Esketamine rather than racemic ketamine.
• A particular nasal spray pump.
• A specified concentration.
• A particular excipient.
• A defined number of sprays.
• A specific treatment duration.
• Inpatient or outpatient administration.
• A formal DSM diagnosis, except that claim 7 narrows the disease to major depressive disorder.
• Concomitant antidepressant therapy, except under claim 5.

How broad are the independent claims in US 9,592,207?

The independent claims are broad in clinical and formulation terms but narrower in patient selection and route of administration.

Route limitation

The claims require intranasal administration. Intravenous, intramuscular, oral, subcutaneous, transdermal, and sublingual ketamine treatments would not literally satisfy the intranasal limitation.

A nasal product may satisfy the route limitation even if it uses a device, formulation, or concentration different from Spravato. The claim does not appear limited to the specific Aptar nasal delivery system used with Spravato.

Active-ingredient limitation

The claims recite ketamine. The scope may include racemic ketamine and, depending on the specification and claim construction, one or both ketamine enantiomers and pharmaceutically acceptable salts. Esketamine is the S-enantiomer of ketamine and is the active ingredient in Spravato.

Whether a particular enantiomer is covered depends on the patent specification, prosecution history, and ordinary meaning assigned to "ketamine." A generic developer cannot assume that a change from racemic ketamine to esketamine avoids the patent.

Patient-selection limitation

The patient must have failed at least two adequate antidepressant treatments. This limitation is commercially important because it aligns closely with the treatment-resistant-depression population identified in the Spravato labeling. [2]

A product administered to patients who have not failed two adequate antidepressant treatments may avoid literal infringement of the independent claims, although other patents or regulatory restrictions could apply.

Efficacy limitation

The dose must be effective to alleviate depression. The claims do not require a specific rating-scale improvement or a particular percentage reduction in symptoms. This functional language may create infringement and proof issues because efficacy must be established from the treatment record, prescribing protocol, clinical evidence, or product labeling.

What do claims 2 through 14 add?

The dependent claims create narrower fallback positions and define commercial treatment parameters.

Claims	Subject matter	Scope effect
2	0.13 to 0.53 mg/kg/day	Narrow weight-based dose range
3	Multiple doses	Repeated administration
4	Single dose administered over seven days	Unusual temporal limitation
5-6	Combination with a second antidepressant agent	Broad adjunctive-treatment coverage
7	Major depressive disorder	Narrows depression diagnosis
8	Up to 250 mg/day	Broad absolute-dose ceiling
9	Two adequate trials in the current episode	Stronger treatment-resistant-depression definition
10	Multiple doses after two current-episode failures	Repeated-treatment subcategory
11	About 0.1 to about 3.0 mg/kg/day	Much broader dose range than claim 2
12	Relief within two hours	Rapid-onset treatment
13	Relief within one day	One-day response
14	Specified prior treatments	SSRIs, SNRIs, tricyclics, MAOIs, or electroconvulsive therapy

Claims 2 and 11 overlap. Claim 2 covers a narrower range within claim 11. Claims 3 and 10 cover repeated dosing, while claim 4 addresses a single dose over a seven-day period. Claim 12 is particularly relevant to ketamine's rapid antidepressant effect and may be asserted where clinical documentation establishes symptom relief within two hours.

Claim 14 is important for treatment-resistant-depression protocols. It expressly identifies common antidepressant classes and electroconvulsive therapy as potentially qualifying prior treatments.

What is the patent expiration date for US 9,592,207?

The reported expiration date for US 9,592,207 is June 30, 2027. The patent was granted on March 14, 2017. Patent-term calculations should be checked against the USPTO Patent Center record, including any patent-term adjustment and terminal disclaimer information. [1]

Event	Date
Patent grant	March 14, 2017
Reported patent expiration	June 30, 2027
FDA approval of Spravato	March 5, 2019
Expected loss of the core patent barrier	June 30, 2027, subject to applicable legal adjustments

The patent expiration date is distinct from FDA regulatory exclusivity. Ketamine was an established active ingredient before Spravato, so the commercial protection for esketamine arose primarily from patents, clinical-data exclusivity, and product-specific regulatory requirements rather than a new chemical entity term for ketamine itself.

What is the Orange Book status of US 9,592,207?

US 9,592,207 has been identified as an Orange Book-listed patent associated with Spravato, esketamine hydrochloride nasal spray. The listing connects the patent to the approved product's use for depressive disorders in adults with major depressive disorder and acute suicidal ideation or behavior, and to treatment-resistant depression, depending on the relevant labeling and listing entry. [3]

The Orange Book listing has four practical consequences:

1. An ANDA applicant must address the listed patent.
2. A Paragraph IV certification can trigger patent litigation.
3. A 30-month stay may delay approval if the NDA holder or patent owner timely sues.
4. A successful challenge, settlement, license, or expiration can determine generic timing.

The Orange Book listing does not prove that every claim is valid or infringed. It identifies the patent as one that the NDA holder represents as covering the approved drug or an approved method of use.

When does Spravato lose exclusivity?

Spravato received FDA approval on March 5, 2019. Its regulatory exclusivity and patent protection have different timelines.

Protection	Approximate endpoint	Business significance
FDA three-year clinical-investigation exclusivity	March 5, 2022	Blocked certain abbreviated applications relying on qualifying new clinical investigations
US Patent 9,592,207	June 30, 2027	Core method-of-treatment patent barrier
Controlled-substance controls	Ongoing	Distribution and prescribing restrictions remain after patent expiry

The three-year exclusivity period did not create a permanent barrier to generic or 505(b)(2) competition. The more significant near-term barrier is the patent estate and any additional Orange Book-listed patents covering formulation, dosing, delivery, or approved methods.

Patent expiry does not automatically authorize commercial launch. A competitor still must obtain FDA approval, satisfy controlled-substance requirements, establish product quality and device performance, and address any unexpired listed patents.

What patent claims are most relevant to Spravato?

Spravato is an esketamine nasal spray administered under healthcare supervision. Its labeled dosing uses repeated intranasal administration, including twice-weekly induction dosing followed by less frequent maintenance dosing. [2]

The commercial overlap with US 9,592,207 is strongest for:

• Adult patients with treatment-resistant depression.
• Patients who failed at least two antidepressant treatments.
• Intranasal esketamine administration.
• Repeated dosing.
• Rapid improvement in depressive symptoms.
• Combination use with an oral antidepressant.

The overlap is weaker or more fact-dependent for:

• Patients treated for acute suicidal ideation or behavior.
• Dosing outside the patent's numerical ranges.
• Racemic ketamine products.
• Compounded nasal formulations.
• Hospital-based or investigational protocols.
• Patients without documented failure of two adequate current-episode treatments.

The patent does not appear to require the exact Spravato strength, device, dosing schedule, or Risk Evaluation and Mitigation Strategy. A competing product may therefore infringe the method claims even if its formulation and device differ from Janssen's product.

What formulation patents protect intranasal ketamine products?

US 9,592,207 is principally a method patent. It does not, based on the supplied claims, protect:

• A specific esketamine composition.
• A nasal-spray formulation.
• A stabilizer or buffer.
• A preservative system.
• A particle-size distribution.
• A spray-pump geometry.
• A dose-counter mechanism.
• A manufacturing process.

Those subjects may be covered by separate patent families owned by Janssen, its affiliates, or third parties. A complete freedom-to-operate review must separate four categories:

Patent category	Typical protected subject
Active ingredient	Esketamine stereochemistry, salts, purity, or compositions
Formulation	Concentration, pH, excipients, stability, and preservative systems
Device	Nasal actuator, metering chamber, dose delivery, and packaging
Clinical use	Treatment-resistant depression, suicidal ideation, maintenance dosing, or rapid response

A generic or 505(b)(2) sponsor that avoids the 9,592,207 method claims may still face formulation, device, or dosing patents. Conversely, a formulation patent does not necessarily block an alternative nasal formulation if the competing product avoids the claimed composition.

Which companies are challenging the Spravato patent estate?

Public patent litigation and Paragraph IV activity must be evaluated from FDA Orange Book records, FDA litigation listings, PACER, and district-court dockets. US 9,592,207 is the principal method patent associated with the early Spravato patent position, but a definitive list of all active challengers requires current docket verification.

The likely competitive groups are:

• Generic pharmaceutical companies pursuing esketamine nasal spray through an ANDA.
• 505(b)(2) sponsors developing alternative intranasal ketamine or esketamine products.
• Academic and specialty-pharmaceutical companies developing racemic ketamine nasal products.
• Developers of subcutaneous, oral, inhaled, or implantable ketamine products that may avoid the intranasal limitation.

A Paragraph IV certification against 9,592,207 would require the applicant to assert that the patent is invalid, unenforceable, or not infringed. The patent holder could respond with a Hatch-Waxman infringement action under 35 U.S.C. § 271(e)(2). [5]

What Paragraph IV risks apply to US 9,592,207?

A Paragraph IV challenger would likely focus on four issues.

Anticipation

Prior art could be asserted to show intranasal ketamine for depression, treatment-resistant depression, or rapid antidepressant response. The critical question would be whether one reference discloses every limitation, including failure of at least two adequate antidepressant treatments.

Obviousness

Obviousness would likely be the central challenge. A challenger could combine:

• Earlier intravenous ketamine studies.
• Earlier intranasal drug-delivery disclosures.
• Treatment-resistant-depression protocols.
• Published evidence of ketamine's rapid antidepressant effect.
• Known dose ranges and repeated-administration schedules.

The patent holder would rely on the specific patient-selection criteria, intranasal route, clinical results, rapid response, and any unexpected treatment benefit.

Written description and enablement

The claims cover a broad range of ketamine doses, treatment schedules, depression diagnoses, and adjunctive agents. A challenger could argue that the specification does not adequately support the full scope, particularly for every listed antidepressant, every dose within the ranges, or every form of ketamine.

Indefiniteness and claim construction

Terms such as "adequate antidepressant treatments," "effective to alleviate depression," "multiple doses," and "over a period of 7 days" may require construction. Claim 4 is especially vulnerable to interpretive dispute because "a single dose ... over a period of 7 days" can raise questions about whether the claim refers to one administration, sustained delivery, or a treatment period.

How strong is the patent estate for US 9,592,207?

US 9,592,207 has meaningful commercial breadth because its independent claims target the treatment protocol rather than a narrow formulation. Its principal strengths are:

• Direct alignment with the treatment-resistant-depression population.
• Coverage of intranasal ketamine generally.
• No requirement for a specific device or formulation.
• Independent claim 15 provides a separate infringement pathway.
• Dependent claims cover repeated dosing, dose ranges, rapid response, and prior treatment classes.

Its principal weaknesses are:

• Ketamine had extensive preexisting antidepressant literature before the patent's filing and prosecution.
• The intranasal route may be challenged as an obvious adaptation of known ketamine therapy.
• "Adequate treatment" and "effective to alleviate depression" may create proof and definiteness disputes.
• The claims may not cover non-intranasal competitive products.
• The patent expires before many potential follow-on products would reach full commercial maturity.

The patent is stronger as a litigation and launch-delay asset than as a permanent technology barrier. Its value depends on whether a competitor's label and actual use require intranasal ketamine for patients who failed two adequate antidepressant treatments.

Does biosimilar risk apply to Spravato?

No. Spravato is a small-molecule drug, not a biologic. Biosimilar provisions under the Public Health Service Act do not apply. [6]

Competition would arise through an ANDA, a 505(b)(2) application, or a separate NDA. An ANDA sponsor would need to demonstrate pharmaceutical equivalence and bioequivalence to the reference product. A 505(b)(2) sponsor could rely partly on FDA findings for Spravato while pursuing differences in formulation, route, device, dosing, or patient population.

How does US 9,592,207 compare with alternative ketamine products?

Product or approach	Route	Relationship to US 9,592,207
Spravato	Intranasal esketamine	Highest direct overlap
Racemic ketamine nasal spray	Intranasal	Potential overlap, depending on interpretation of ketamine and approved use
IV ketamine	Intravenous	Avoids the intranasal limitation
IM ketamine	Intramuscular	Avoids the intranasal limitation
Oral ketamine	Oral	Avoids the intranasal limitation
New nasal delivery device	Intranasal	Device change alone may not avoid the method claims
Intranasal product for pain	Intranasal	May avoid depression and treatment-resistant-depression limitations

Route and indication design-around strategies may reduce exposure, but they do not eliminate other patent, regulatory, clinical, or controlled-substance barriers.

What generic launch scenarios exist after patent expiry?

The principal launch scenarios are:

1. At-risk launch before June 30, 2027. A challenger launches after receiving FDA approval but before final patent resolution. This exposes the sponsor to damages and possible injunctive relief.
2. Launch after patent expiry. The sponsor waits for expiration and avoids core 9,592,207 infringement risk, subject to remaining patents.
3. License or settlement. The sponsor reaches an agreement with the patent holder for an authorized or date-certain launch.
4. Non-infringing 505(b)(2) product. A sponsor develops a different route, indication, dose, or formulation.
5. Compounded or clinical-use product. A product is used outside the approved commercial pathway, although compounding, state law, FDA enforcement, and patent exposure remain relevant.

The most commercially valuable design-around is a non-intranasal ketamine product. That strategy avoids the central route limitation but requires a separate clinical and regulatory program.

What licensing deals affect the patent?

The ketamine depression technology originated in government-supported research associated with the National Institute of Mental Health and the U.S. Department of Health and Human Services. Janssen developed and commercialized esketamine as Spravato through its Janssen pharmaceutical operations. [1, 2]

The relevant commercial rights should be separated into:

• Ownership of US 9,592,207.
• Licenses to the underlying government-developed technology.
• Janssen's product and formulation rights.
• Any sublicenses involving formulation, device, or manufacturing patents.
• Settlement or authorized-generic agreements with Paragraph IV challengers.

A license to one patent family does not necessarily grant freedom to operate under other formulation, device, or method-of-use patents.

Key Takeaways

• US 9,592,207 is a method-of-treatment patent for intranasal ketamine in depression after failure of at least two adequate antidepressant treatments.
• Claims 1 and 15 are the principal commercial claims.
• The patent covers treatment use, not merely ketamine, a nasal formulation, or a delivery device.
• Spravato has the closest commercial overlap because it is intranasal esketamine for treatment-resistant depression.
• The reported expiration date is June 30, 2027.
• FDA exclusivity for Spravato expired earlier and is separate from patent protection.
• Biosimilar competition does not apply because Spravato is a small molecule.
• A Paragraph IV challenge would likely focus on obviousness, anticipation, written description, enablement, and claim construction.
• Non-intranasal ketamine products have the clearest route-based design-around, but they require separate regulatory and clinical support.
• Patent expiry does not eliminate remaining formulation, device, dosing, or manufacturing barriers.

FAQs

Can a racemic ketamine nasal spray infringe US 9,592,207?

Yes. The patent claims recite ketamine and are not expressly limited in the supplied claims to esketamine. The literal and construed scope of racemic ketamine would depend on the specification, prosecution history, and court interpretation.

Does using a different nasal spray device avoid US 9,592,207?

Not necessarily. The supplied claims do not require a particular device. A different actuator or pump could still be used in a treatment method that satisfies the intranasal ketamine and treatment-resistant-depression limitations.

Does off-label intranasal ketamine avoid the patent?

No. Off-label use does not automatically avoid patent infringement. The relevant question is whether the method satisfies the asserted claim limitations, including intranasal ketamine administration and treatment after failure of at least two adequate antidepressant treatments.

Can a company avoid the patent by treating depression after only one failed antidepressant?

That may avoid the specific two-treatment limitation in the independent claims, but the company could face other patents, regulatory restrictions, inducement theories, or different infringement allegations depending on product labeling and actual use.

Is FDA approval enough to launch a generic esketamine product?

No. FDA approval and patent clearance are separate requirements. An approved ANDA may remain subject to patent litigation, a 30-month stay, settlement restrictions, or later claims involving formulation, device, dosing, or manufacturing patents.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,592,207, Methods of treating depression using ketamine.
2. U.S. Food and Drug Administration. (2025). Spravato prescribing information. Janssen Pharmaceuticals, Inc.
3. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (2019, March 5). FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor's office or clinic.
5. Hatch-Waxman Amendments, 35 U.S.C. § 271(e)(2).
6. Public Health Service Act, 42 U.S.C. § 262.

Drugs Protected by US Patent 9,592,207

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Janssen Pharms	SPRAVATO	esketamine hydrochloride	SPRAY;NASAL	211243-001	Mar 5, 2019		RX	Yes	Yes						TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULT IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
Janssen Pharms	SPRAVATO	esketamine hydrochloride	SPRAY;NASAL	211243-001	Mar 5, 2019		RX	Yes	Yes						TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULTS

International Family Members for US Patent 9,592,207

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007229866
China	101466364
European Patent Office	2012762
Japan	2009530385