Details for Patent: 9,125,910

Which drugs does patent 9,125,910 protect, and when does it expire?

Patent 9,125,910 protects TRINTELLIX and is included in one NDA.

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

This patent has ninety-three patent family members in thirty-four countries.

Summary for Patent: 9,125,910

Title:	1-[2-(2,4 dimethylphenylsulfanyl)-phenyl]piperazine as a compound with combined serotonin reuptake, 5-HT3 and 5-HT1A activity for the treatment of cognitive impairment
Abstract:	This disclosure relates to a method of treating a disease selected from the group consisting of Alzheimer's disease, cognitive impairment, and attention deficit hyperactivity disorder (ADHD). The method includes administering a therapeutically effective amount of Compound I or a pharmaceutically acceptable salt thereof to patient in need thereof, in which Compound I is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine.
Inventor(s):	Benny Bang-Andersen, Arne Mork, Tine Bryan Stensbol, Andre Faldt
Assignee:	H Lundbeck AS
Application Number:	US14/481,000
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,125,910
Patent Claim Types: see list of patent claims	Use;

United States Patent 9,125,910: Scope, Claims, Expiration, and Vortioxetine Patent Landscape

U.S. Patent No. 9,125,910 protects the use of vortioxetine, identified in the patent as Compound I, for treating cognitive impairment in patients with depression. The claims focus on impairment in processing speed, executive function, attention, or verbal learning and memory. The patent does not claim vortioxetine as a chemical compound, its general antidepressant use, or every use in cognitive disorders.

The patent was issued to H. Lundbeck A/S and has an estimated patent expiration date of November 15, 2033, subject to any applicable patent-term adjustment, patent-term extension, terminal disclaimer, or later legal event. The principal commercial product associated with the patent is Trintellix, formerly marketed as Brintellix, containing vortioxetine hydrobromide.

What does U.S. Patent 9,125,910 protect?

The patent protects a method-of-use regimen requiring four core elements:

1. The patient has depression.
2. The patient has cognitive impairment.
3. The impairment involves at least one specified cognitive domain.
4. The patient receives Compound I or a pharmaceutically acceptable salt in a therapeutically effective amount.

The independent claim is directed to treating cognitive impairment involving decline in:

• Speed of processing;
• Executive function;
• Attention; or
• Verbal learning and memory.

The claimed method must alleviate a symptom or complication of the cognitive impairment or delay its progression.

This is a therapeutic-use patent. It does not cover the chemical structure of vortioxetine itself. It also does not require a particular dosage, dosage frequency, formulation, route of administration, treatment duration, cognitive test, or degree of improvement.

What is Compound I in Patent 9,125,910?

Compound I is:

1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine

This is vortioxetine, also known as Lu AA21004. Claim 2 and several dependent claims specifically cover the hydrobromide salt, which is the active pharmaceutical ingredient used in Trintellix.

The claims also identify the following pharmaceutically acceptable salts:

• Hydrobromide;
• Hydrochloride;
• Mesylate;
• Fumarate;
• Maleate;
• Meso-tartrate;
• L-(+)-tartrate;
• D-(−)-tartrate;
• Sulphate;
• Phosphate; and
• Nitrate.

How broad is claim 1 of U.S. Patent 9,125,910?

Claim 1 is commercially significant but narrower than a general vortioxetine claim.

Claim element	Scope
Active agent	Compound I, vortioxetine, or a pharmaceutically acceptable salt
Patient condition	Patient diagnosed with depression
Cognitive condition	Cognitive impairment involving at least one claimed domain
Cognitive domains	Processing speed, executive function, attention, or verbal learning and memory
Therapeutic result	Alleviation of a symptom or complication, or delay of progression
Dose	No specific dose stated
Route	No specific route stated
Formulation	No specific formulation stated
Disease subtype	Broad depression category in claim 1; narrower subtypes in dependent claims

Claim 1 does not expressly require major depressive disorder, treatment-resistant depression, bipolar depression, or postnatal depression. Those conditions appear in dependent claims 3 and 7 through 10.

The claim also does not expressly require that the cognitive impairment be diagnosed as a separate disease. A generic product label or clinical use directed to depression-related cognitive impairment could create infringement risk if the prescribed use falls within the claim limitations.

What do claims 2 through 10 add?

The dependent claims narrow the patient population or the salt form.

Claim	Limitation
1	Core method for cognitive impairment in a patient diagnosed with depression
2	Hydrobromide salt
3	Major depressive disorder
4	Listed pharmaceutically acceptable salts
5	Listed salts in a patient with major depressive disorder
6	Hydrobromide salt in a patient with major depressive disorder
7	Generalized depression
8	Postnatal depression
9	Depression associated with bipolar disorder
10	Treatment-resistant depression

Claims 3, 6, and 10 are particularly relevant to commercial prescribing because they cover major depressive disorder, vortioxetine hydrobromide, and treatment-resistant depression. Claim 10 may be important in an ANDA dispute because a generic applicant could attempt to omit treatment-resistant depression from labeling while retaining approval for other depressive disorders.

When does Patent 9,125,910 expire?

The patent has an estimated expiration date of November 15, 2033, based on the 20-year term calculated from the relevant international or nonprovisional filing date reflected in the patent family. The exact enforceable date depends on the USPTO patent-term calculation and any recorded adjustments or disclaimers.

Event	Date
Earliest relevant priority date	November 15, 2012
U.S. filing or national-stage timing	2013
Patent issued	September 8, 2015
Estimated ordinary expiration	November 15, 2033
Patent type	Method-of-use patent

The patent’s remaining value depends on whether it is listed in the FDA Orange Book for an approved vortioxetine product, whether the claims remain enforceable, and whether generic applicants have filed Paragraph IV certifications.

A patent expiration date alone does not establish the earliest lawful generic launch date. Generic entry can occur through patent expiry, a court judgment, a settlement license, a successful invalidity or noninfringement ruling, or an authorized generic arrangement.

What is the Orange Book status of U.S. Patent 9,125,910?

The relevant FDA regulatory question is whether Patent 9,125,910 is listed for Trintellix and whether its use code corresponds to treatment of cognitive dysfunction in depression.

The FDA Orange Book distinguishes among:

• Active ingredient patents;
• Drug-product or formulation patents; and
• Method-of-use patents.

For a listed method-of-use patent, an ANDA applicant may file a Paragraph IV certification asserting that the patent is invalid, unenforceable, or will not be infringed. The applicant may also use a section viii statement to carve out the patented indication if FDA labeling permits a non-infringing approval.

A section viii carve-out is more difficult where the patented cognitive-use concept overlaps with the approved depression indication or where the innovator’s labeling, promotional materials, or clinical positioning makes the cognitive use central to the product.

The Orange Book listing should be reviewed together with:

• The patent-use code;
• The approved Trintellix labeling;
• Any pediatric exclusivity notation;
• Any patent-term adjustment;
• Any FDA-listed later patents; and
• Any current ANDA certification records.

How does Patent 9,125,910 affect Paragraph IV challenges?

A Paragraph IV challenge could target the patent on several grounds.

Noninfringement

A generic applicant could argue that its proposed labeling does not direct treatment of cognitive impairment in the claimed domains. A label limited to depression treatment, without cognitive impairment language, may reduce direct infringement exposure. The analysis would still consider whether the labeling or prescribing information encourages the patented use.

A generic applicant could also contest whether the patient has a qualifying cognitive impairment or whether the claimed cognitive domains are met.

Invalidity for anticipation

The challenger could search for earlier clinical publications, patent disclosures, or regulatory documents describing vortioxetine treatment of depression-associated cognitive impairment before the relevant priority date.

Anticipation would require a single prior-art reference to disclose every claim element, including:

• Depression;
• The specified cognitive impairment;
• Vortioxetine or a covered salt;
• Therapeutic administration; and
• Alleviation of symptoms, complications, or progression delay.

Obviousness

Obviousness is likely to be the principal validity issue. The analysis would consider whether a skilled person would have expected vortioxetine to treat cognitive impairment in depressed patients based on:

• Vortioxetine’s pharmacology;
• Prior antidepressant and cognitive-function data;
• Serotonergic receptor activity;
• Published clinical studies;
• Known cognitive effects of depression; and
• A reasonable expectation of success.

The patent’s defense would likely rely on the claimed clinical population and the specific cognitive domains, together with evidence that the results were not predictable from vortioxetine’s general antidepressant activity.

Written description and enablement

The claims cover multiple depression subtypes and multiple cognitive domains. A challenger could argue that the specification does not adequately support or enable the full breadth of the claims, particularly for generalized depression, postnatal depression, bipolar depression, and treatment-resistant depression if the clinical evidence was concentrated in major depressive disorder.

The patent holder would respond that the specification provides a common mechanism and sufficient clinical or experimental support across the claimed genus.

What formulations are protected by Patent 9,125,910?

Patent 9,125,910 is not primarily a formulation patent. It does not require:

• A tablet;
• An immediate-release dosage form;
• A controlled-release formulation;
• A specific excipient;
• A particular dissolution profile;
• A specific particle size;
• A coating; or
• A manufacturing process.

Its salt claims cover chemical forms of vortioxetine, but salt coverage is not the same as protection for a finished pharmaceutical formulation.

A generic tablet containing vortioxetine hydrobromide could still implicate the patent if the generic labeling or use instructions fall within the method claims. Conversely, a formulation design that avoids a particular excipient or release profile would not, by itself, avoid infringement if the patented method is practiced.

How does Patent 9,125,910 compare with earlier vortioxetine patents?

The vortioxetine estate has multiple layers. The earliest patents concern the compound itself and broad therapeutic use. Later patents focus on specific formulations, salts, indications, or clinical advantages.

Patent layer	Typical subject matter	Commercial effect
Composition-of-matter patents	Vortioxetine chemical structure	Broadest early protection
Salt and solid-form patents	Hydrobromide and other forms, crystalline materials	Limits alternative API forms
Antidepressant-use patents	Treatment of depressive disorders	Supports product labeling
Cognitive-use patents	Cognitive impairment associated with depression	Extends indication-specific protection
Formulation patents	Tablets, release characteristics, excipients	Raises product-substitution barriers
Manufacturing patents	Synthesis, purification, crystallization	May constrain API suppliers

Patent 9,125,910 is narrower than a composition patent but potentially later-expiring. That structure is common in small-molecule portfolios: the original compound patent expires earlier, while later clinical-use patents can remain relevant to generic labeling and commercial launch strategy.

How strong is the patent estate for vortioxetine?

The estate is strongest where it combines:

1. An approved product with established market demand;
2. A listed method-of-use patent;
3. Evidence linking the product to the patented cognitive indication;
4. Multiple overlapping patent families; and
5. Regulatory exclusivity or settlement-based launch restrictions.

Patent 9,125,910 has several strengths:

• It identifies a specific active ingredient.
• It defines clinically recognizable cognitive domains.
• It covers multiple depression subtypes.
• It includes the commercially relevant hydrobromide salt.
• It does not depend on a narrowly defined dose or formulation.
• It potentially reaches use of generic vortioxetine where labeling directs the patented indication.

Its principal vulnerabilities are claim breadth and proof. The patent must support the full range of depression subtypes, cognitive domains, and therapeutic outcomes. In litigation, the patent holder would also need to prove that the generic product’s proposed labeling induces or contributes to performance of the claimed method.

Are biosimilar risks relevant to vortioxetine?

No. Vortioxetine is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an abbreviated new drug application under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Biologics Price Competition and Innovation Act.

Competitive risk therefore comes from:

• ANDA applicants;
• Paragraph III certifications;
• Paragraph IV certifications;
• Label carve-outs;
• Authorized generics; and
• Settlement licenses.

The principal regulatory barrier is the listed patent estate, not biosimilar interchangeability or biologic exclusivity.

Which companies may challenge the vortioxetine patents?

Potential challengers are generic pharmaceutical companies that develop vortioxetine tablets and file ANDAs. Companies active in U.S. antidepressant generics have historically included Teva, Viatris, Dr. Reddy’s Laboratories, Alembic, Zydus, Sun Pharma, and other ANDA sponsors.

A company’s development activity does not establish that it filed a Paragraph IV certification. The operative evidence is an FDA approval record, a notice letter, a patent litigation complaint, a district court docket, or a settlement agreement.

The main litigation targets would include:

• H. Lundbeck A/S;
• Takeda Pharmaceuticals U.S.A., Inc., as the U.S. commercial partner for Trintellix; and
• Related patent owners or exclusive licensees identified in the Orange Book or litigation pleadings.

What patent litigation and settlements affect generic launch?

A Paragraph IV notice can trigger a 45-day period for filing an infringement action. A timely action may impose a 30-month stay of FDA approval, subject to statutory exceptions and court action.

Settlement agreements may provide:

• A fixed generic entry date;
• A license before patent expiration;
• An authorized generic arrangement;
• Restrictions tied to specific claims or indications; or
• A resolution limited to one ANDA applicant.

The commercial launch date cannot be inferred from Patent 9,125,910 alone. It depends on the interaction of the entire listed estate, ANDA certifications, litigation outcomes, and any confidential or public settlement terms.

What generic launch scenarios exist for vortioxetine?

Full-label launch after patent expiry

The generic company waits until the last relevant patent expires and markets vortioxetine for all approved indications. This is the lowest litigation-risk scenario but may sacrifice substantial market share to earlier entrants.

Carved-out launch

The generic seeks approval for depression while excluding the patented cognitive-impairment use. This strategy depends on whether FDA accepts a section viii carve-out and whether the remaining label avoids inducing the patented method.

At-risk launch

The generic launches before final resolution of the patent dispute. The company faces potential damages, an injunction, and product withdrawal if the patent is upheld and found infringed.

Licensed early entry

The generic receives a license under a settlement agreement. The agreement may permit entry before November 2033, with terms varying by applicant.

Authorized generic competition

The innovator or its commercial partner launches an authorized generic, reducing the price advantage and revenue opportunity available to an independent ANDA entrant.

What is the revenue exposure from Patent 9,125,910?

The patent’s revenue exposure is tied to the value of the Trintellix franchise and the extent to which cognitive benefits support prescribing, payer positioning, and differentiation from older SSRIs and SNRIs.

The patent does not protect all Trintellix revenue. It protects only sales associated with use within the claimed cognitive-depression population. Revenue attributable to general antidepressant treatment may depend on separate patents, regulatory exclusivities, or no longer-protected product features.

The economic impact is nevertheless potentially material because a method-of-use patent can delay broad generic substitution if:

• The patented use is prominent in labeling;
• Physicians prescribe for cognitive symptoms;
• The product’s commercial differentiation depends on cognition;
• Carving out the use would materially reduce the generic label; or
• Other patents create overlapping barriers.

What is the geographic coverage of Patent 9,125,910?

The patent provides rights only in the United States. Comparable protection may exist in other jurisdictions through related applications or national-phase filings, but U.S. Patent 9,125,910 does not itself create rights in Europe, Japan, Canada, Australia, or other markets.

A global freedom-to-operate review should separately examine:

• European Patent Office family members;
• United Kingdom national rights;
• Canadian and Australian patents;
• Japan and South Korea;
• China and other manufacturing jurisdictions; and
• Patent term and regulatory-extension rules in each market.

The U.S. method claims are most relevant to U.S. prescribing, ANDA approval, and U.S. distribution.

Key Takeaways

• U.S. Patent 9,125,910 is a method-of-use patent covering vortioxetine treatment of specified cognitive impairment in patients with depression.
• The independent claim covers impairment in processing speed, executive function, attention, or verbal learning and memory.
• Claims 2 through 10 add salt limitations and depression subtypes, including major depressive disorder, postnatal depression, bipolar-associated depression, and treatment-resistant depression.
• The patent does not claim vortioxetine’s chemical structure or general antidepressant use.
• The estimated expiration date is November 15, 2033, subject to the official USPTO term calculation and any recorded adjustments.
• Generic companies would principally evaluate Paragraph IV, section viii, invalidity, noninfringement, and settlement strategies.
• Vortioxetine is a small molecule, so biosimilar rules do not apply.
• The patent’s commercial strength depends on Orange Book listing, use-code wording, generic labeling, evidence supporting the cognitive indication, and the rest of the vortioxetine patent estate.
• Patent 9,125,910 is potentially important as a later-expiring clinical-use patent even though earlier composition patents may have expired.

FAQs About U.S. Patent 9,125,910

Does Patent 9,125,910 cover Trintellix itself?

No. It covers specified methods of using vortioxetine for cognitive impairment in depressed patients. Separate composition, product, formulation, or use patents may cover other aspects of Trintellix.

Can a generic launch vortioxetine for depression without infringing this patent?

Potentially. A generic may seek a section viii carve-out for the patented cognitive use. The result depends on the proposed labeling, FDA-approved indications, use code, and whether the labeling induces the claimed method.

Does claim 10 cover all treatment-resistant depression patients?

Claim 10 narrows claim 1 to treatment-resistant depression. The patient must still have the claimed cognitive impairment, receive vortioxetine or a covered salt, and satisfy the remaining limitations of claim 1.

Is vortioxetine hydrobromide required for infringement?

No. Claim 1 covers Compound I and pharmaceutically acceptable salts. Claim 2 separately identifies the hydrobromide salt, while claim 4 lists several additional salts.

Does the patent protect use of vortioxetine in bipolar depression?

Claim 9 expressly covers depression associated with bipolar disorder, but only when the other limitations inherited from claim 1 are satisfied, including the specified cognitive impairment.

References

1. United States Patent No. 9,125,910. (2015). Use of vortioxetine for the treatment of cognitive dysfunction. United States Patent and Trademark Office.

2. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

4. U.S. Food and Drug Administration. (2013). Trintellix (vortioxetine) prescribing information. Takeda Pharmaceuticals U.S.A., Inc.

5. United States Code, 35 U.S.C. §§ 154, 271, and 282.

6. United States Code, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 9,125,910

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Takeda Pharms Usa	TRINTELLIX	vortioxetine hydrobromide	TABLET;ORAL	204447-001	Sep 30, 2013		RX	Yes	No	9,125,910*PED				Y
Takeda Pharms Usa	TRINTELLIX	vortioxetine hydrobromide	TABLET;ORAL	204447-002	Sep 30, 2013		RX	Yes	No	9,125,910*PED				Y
Takeda Pharms Usa	TRINTELLIX	vortioxetine hydrobromide	TABLET;ORAL	204447-003	Sep 30, 2013		DISCN	Yes	No	9,125,910*PED				Y
Takeda Pharms Usa	TRINTELLIX	vortioxetine hydrobromide	TABLET;ORAL	204447-004	Sep 30, 2013		RX	Yes	Yes	9,125,910*PED				Y

International Family Members for US Patent 9,125,910

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	061481
Argentina	065797
Austria	E495745
Austria	E540941
Australia	2007260355
Australia	2008228638