Details for Patent: 9,125,909

Which drugs does patent 9,125,909 protect, and when does it expire?

Patent 9,125,909 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: 9,125,909

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 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine or a pharmaceutically acceptable salt thereof in a crystalline form.
Inventor(s):	Benny Bang-Andersen, Andre Faldt, Arne Mork, Heidi Lopez De Diego, Rene Holm, Tine Bryan Stensbol
Assignee:	H Lundbeck AS
Application Number:	US14/326,725
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,125,909
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 9,125,909: Vortioxetine Cognitive-Impairment Claims, Patent Scope, Expiration and Generic Risk

US Patent No. 9,125,909 protects the use of crystalline vortioxetine, particularly vortioxetine hydrobromide, to treat cognitive impairment in patients diagnosed with depression. The patent does not broadly cover vortioxetine for depression. Its independent claim requires a specific cognitive indication, a depressed patient population, crystalline active ingredient, therapeutic administration, and an improvement, alleviation, or delay relating to cognitive impairment. The patent was assigned to H. Lundbeck A/S and issued on September 8, 2015. Its earliest priority date is in 2011, producing an estimated patent-term expiration in 2032, subject to the official USPTO term calculation and any terminal disclaimer or adjustment.

The principal commercial risk is an ANDA applicant seeking approval for vortioxetine tablets with a Paragraph IV certification. A generic applicant may avoid literal infringement by omitting the patented cognitive indication from its proposed label, although induced-infringement risk remains if the product is marketed or prescribed for the patented use.

What does US Patent 9,125,909 protect?

The patent protects a method of treating cognitive impairment associated with depression using crystalline Compound I or a pharmaceutically acceptable salt.

Compound I is:

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

This compound is vortioxetine, also known as Lu AA21004. The marketed active pharmaceutical ingredient is generally vortioxetine hydrobromide.

The core claim requires all of the following:

Required limitation	Scope
Patient condition	The patient must be diagnosed with depression
Cognitive disorder	Cognitive impairment involving decline in processing speed, executive function, attention, or verbal learning and memory
Active ingredient	Compound I, vortioxetine, or a pharmaceutically acceptable salt
Solid-state requirement	Compound I or its salt must be in a crystalline form
Administration	A therapeutically effective amount must be administered
Result	The treatment must alleviate a symptom or complication or delay progression of the cognitive impairment

Claim 1 is therefore a method-of-use claim with a product-form limitation. It is not a general composition claim, a broad vortioxetine treatment claim, or a claim covering every patient with depression.

The claim is potentially infringed only when each limitation is satisfied. A product containing amorphous vortioxetine, for example, would present a factual issue under the crystalline-form limitation. A product used solely for major depressive disorder without a cognitive-impairment indication would present a separate claim-scope issue.

What cognitive impairments are covered by Patent 9,125,909?

The independent claim identifies four cognitive domains:

1. Speed of processing.
2. Executive function.
3. Attention.
4. Verbal learning and memory.

The claim language is not limited to one specific diagnostic instrument or test. The infringement analysis would likely focus on whether the patient has a clinically recognized decline in one or more of those domains and whether treatment is directed to alleviating or delaying that impairment.

The patent does not require that the cognitive impairment constitute dementia, mild cognitive impairment, Alzheimer’s disease, or another independent neurologic diagnosis. The claimed cognitive impairment is presented in the context of depression.

The result limitation also matters. Administration alone is insufficient. The claimed method requires that treatment alleviate a symptom or complication of the cognitive impairment or delay its progression. Clinical-trial endpoints, prescribing materials, investigator instructions, medical claims, and promotional statements could become relevant evidence.

How do claims 2 through 11 narrow the patent scope?

Claims 2 through 11 narrow the independent method claim by specifying salts, formulation characteristics, depression subtypes, or combinations of those limitations.

Claim	Added limitation	Practical effect
1	Crystalline Compound I or salt for cognitive impairment in a depressed patient	Broadest enforceable method claim
2	Listed pharmaceutically acceptable salts	Limits salt selection to hydrobromide, hydrochloride, mesylate, fumarate, maleate, tartrate, sulfate, phosphate, or nitrate
3	Vortioxetine hydrobromide	Directly targets the marketed HBr form
4	Wet-granulated tablet with specified excipients	Adds manufacturing process and formulation limitations
5	Quantitative excipient ranges	Covers a defined range composition
6	Approximately 5% HBr salt and approximately 39%, 20%, 3%, 25%, 3%, 4%, and 1% excipients	Targets a specific commercial-type tablet formulation
7	Generalized depression	Narrows the depression diagnosis
8	Major depressive disorder	Aligns most closely with the approved Trintellix indication
9	Postnatal depression	Covers a specific depressed population
10	Depression associated with bipolar disorder	Covers a bipolar-associated depression population
11	Treatment-resistant depression	Covers patients whose depression has failed prior treatment

Claims 7 through 11 depend on claim 1. A product or treatment method falling within one of those categories must still satisfy the crystalline vortioxetine and cognitive-impairment requirements in claim 1.

What formulation patents are covered by US Patent 9,125,909?

Claims 4 through 6 protect a tablet formulation containing vortioxetine hydrobromide and a defined excipient system.

The listed ingredients are:

• Anhydrous calcium hydrogen phosphate.
• Corn starch.
• PVP-VA copolymer.
• Microcrystalline cellulose.
• Sodium starch glycolate.
• Talc.
• Magnesium stearate.

Claim 4 requires a tablet prepared by wet granulation. Claims 5 and 6 specify composition percentages.

Claim 6 describes the approximate formulation:

Component	Approximate percentage
Vortioxetine hydrobromide	5%
Anhydrous calcium hydrogen phosphate	39%
Corn starch	20%
PVP-VA copolymer	3%
Microcrystalline cellulose	25%
Sodium starch glycolate	3%
Talc	4%
Magnesium stearate	1%
Total	Approximately 100%

The use of “comprises” generally makes the formulation claims open-ended. Additional excipients may not avoid infringement if the claimed ingredients, process, and percentage limitations remain present. A formulation that changes the excipient system, uses direct compression instead of wet granulation, or falls outside the stated ranges may reduce literal-infringement exposure, although the doctrine of equivalents could remain relevant.

Claims 4 through 6 are narrower than claim 1 and may be harder to enforce against a generic product if the ANDA formulation does not disclose the same excipients or manufacturing process. They may still be important in discovery because an ANDA applicant’s confidential formulation and manufacturing information can determine whether the claims are implicated.

When does US Patent 9,125,909 expire?

The patent issued on September 8, 2015. Based on the disclosed priority history beginning in 2011, the ordinary 20-year patent term is expected to end in approximately 2032. The exact expiration date depends on:

• The earliest effective nonprovisional or international filing date.
• Patent-term adjustment.
• Any terminal disclaimer.
• The official USPTO patent-term calculation.

The projected 2032 expiration is materially later than the principal early-generation vortioxetine composition patents. It gives the patent potential importance as a late-expiring method-of-use patent even after generic approval for depression may become possible.

The patent term should not be confused with FDA regulatory exclusivity. Patent expiration and FDA exclusivity are separate legal mechanisms.

What is the FDA and Orange Book status of vortioxetine?

Vortioxetine hydrobromide was approved by FDA in 2013 under the brand name Brintellix for major depressive disorder. The brand was renamed Trintellix in the United States in 2016 because of medication-name confusion concerns. The FDA-approved indication is the treatment of major depressive disorder in adults. The product is marketed by Takeda Pharmaceuticals U.S.A., Inc., with Lundbeck as the originator partner.

The approved label does not establish a broad FDA indication for treating cognitive impairment in depressed patients. Patent 9,125,909 therefore covers a use that is narrower than the principal approved depression indication.

Regulatory issue	Status
Active ingredient	Vortioxetine hydrobromide
Brand	Trintellix
Original US approval	2013
FDA-approved indication	Major depressive disorder in adults
Dosage form	Oral tablets
Primary commercial strength	5 mg, 10 mg, 15 mg, and 20 mg tablets
Cognitive-impairment indication	Not established as a broad approved Trintellix indication
Regulatory pathway for generics	ANDA, subject to reference-product exclusivity and listed patents
Biosimilar pathway	Not applicable

Whether Patent 9,125,909 is currently listed in the Orange Book, and the use code assigned to it, must be determined from the current FDA Approved Drug Products with Therapeutic Equivalence Evaluations database. Orange Book listing is significant because it can trigger a 30-month stay when the NDA holder or patent owner brings a timely infringement action following a Paragraph IV notice. Listing does not itself prove that every claim is enforceable or infringed.

How do Paragraph IV challenges apply to Patent 9,125,909?

An ANDA applicant seeking approval for generic vortioxetine may certify under Paragraph IV that a listed patent is invalid, unenforceable, or will not be infringed. If the applicant sends a Paragraph IV notice and the patent owner files suit within the statutory period, FDA approval may be stayed for up to 30 months, subject to statutory exceptions and litigation developments.

For this patent, the principal Paragraph IV arguments would likely focus on four issues:

Indication carve-out

The ANDA applicant may omit cognitive-impairment language from its proposed label through a section viii statement or other labeling strategy, depending on the Orange Book use code and the relationship between the patented use and the approved indication.

The central issue would be whether the remaining label still encourages use for the patented cognitive-improvement method. Instructions concerning cognition, executive function, attention, memory, or treatment-resistant depression could increase inducement exposure.

Crystalline-form limitation

The applicant may argue that its proposed product does not contain the claimed crystalline form. That argument depends on solid-state characterization, polymorph identity, salt form, manufacturing controls, and whether the claim requires a particular crystal form or merely crystallinity.

The claims supplied here require that Compound I or its salt be in a crystalline form. They do not, on their face, identify a particular polymorph by X-ray diffraction pattern.

Treatment-result limitation

The applicant may challenge the requirement that treatment alleviate a symptom or complication or delay progression of cognitive impairment. Method-of-treatment claims can raise issues concerning whether the result is a claim limitation, whether it is inherently satisfied, and what evidence establishes the result.

Written description and enablement

The applicant may challenge whether the specification adequately supports the full range of claimed depressive populations, cognitive domains, salts, crystal forms, and outcomes. The breadth of claim 1 compared with the narrower formulation and patient-subgroup claims would be relevant.

Which companies may challenge Trintellix patent rights?

Generic companies seeking approval for vortioxetine products are the likely challengers. Public generic activity has involved companies pursuing ANDA products for vortioxetine tablets, including major US and international generic manufacturers. The relevant legal record is product-specific because an ANDA applicant may challenge some patents and not others, and may use a Paragraph III certification for patents it accepts.

A competitive assessment should distinguish:

• Challenges to early vortioxetine compound or composition patents.
• Challenges to crystalline-form or salt patents.
• Challenges to formulation patents.
• Challenges to cognitive-impairment method claims.
• Label carve-outs that avoid the patented use.
• Settlements that authorize a future generic launch before patent expiration.

A Paragraph IV notice is not the same as a commercial launch. The applicant may be blocked by a 30-month stay, preliminary injunction, settlement, or an adverse district-court judgment.

What patent litigation and settlements affect vortioxetine?

Vortioxetine patent litigation has centered on ANDA filings against Trintellix-related patent rights. The key litigation questions are typically claim construction, crystalline-form identity, formulation overlap, induced infringement, and validity under obviousness, anticipation, written-description, and enablement doctrines.

A settlement can establish an agreed generic entry date without invalidating the patent. Settlement terms may also include:

• A license for one or more strengths.
• An authorized-generic arrangement.
• Restrictions on launch before a specified date.
• A covenant not to sue for noncommercial activities.
• Different entry dates for different manufacturers.

Patent 9,125,909 should be analyzed separately from the earlier vortioxetine patents because a settlement concerning a composition patent may not resolve a later method-of-use claim unless the agreement expressly covers it.

How does the patent estate compare with competing antidepressant estates?

Vortioxetine has a layered but relatively concentrated patent estate.

Estate layer	Typical protection	Business significance
Core compound	Vortioxetine molecule and related compounds	Usually earliest-expiring protection
Salt and solid state	Hydrobromide salt and crystalline forms	Can delay or complicate generic substitution
Formulation	Tablet composition and manufacturing process	Depends heavily on ANDA formulation disclosure
Method of use	Cognitive impairment in depressed patients	Potentially extends protection beyond core product patents
Regulatory exclusivity	FDA exclusivity tied to approval	Separate from patent duration
Label protection	Approved indication and use code	Determines practical value of a method patent

Patent 9,125,909 is commercially stronger than a narrow excipient claim because claim 1 reaches the underlying cognitive-use method across multiple acceptable salts and depression subtypes. It is commercially weaker than a composition patent if a generic can enter with a label that omits the protected cognitive use.

Compared with biologics, vortioxetine has no biosimilar pathway. It is a small-molecule drug, and competition proceeds through ANDAs and therapeutic-equivalence determinations rather than biosimilar applications.

How strong is the patent estate for Patent 9,125,909?

The strongest part of the patent is claim 1. It combines a commercially relevant active ingredient with a defined patient population and a potentially differentiated therapeutic objective. Claim 3 is also commercially relevant because it targets vortioxetine hydrobromide, the marketed salt.

The principal weaknesses are:

• The cognitive indication is narrower than the FDA-approved depression indication.
• The claim requires a diagnosed depressed patient with specified cognitive impairment.
• The crystalline-form requirement may create factual and scientific disputes.
• A generic may seek a label carve-out.
• The treatment-outcome language may create proof issues.
• Claims 4 through 6 depend on exact formulation and manufacturing details.
• Claims 7 through 11 are narrower and may be easier to design around.

Relative claim strength

Claim group	Relative scope	Main vulnerability
Claim 1	Broadest	Indication, crystallinity, and outcome limitations
Claims 2-3	Moderate	Salt-specific limitations
Claims 4-6	Narrow	Exact excipients, ranges, and wet granulation
Claims 7-11	Narrow	Specific depression populations

The patent’s practical value depends heavily on whether the cognitive-use claims are listed in the Orange Book and whether the use code permits an effective label carve-out.

What generic launch scenarios exist for vortioxetine?

Three launch scenarios are most relevant.

Scenario 1: Full-label approval after patent resolution

The generic applicant challenges the listed patents, obtains a favorable judgment, reaches a license, or waits for expiration. It launches with labeling substantially corresponding to the reference product.

This scenario creates the highest direct substitution risk for Trintellix.

Scenario 2: Skinny-label launch

The applicant removes the patented cognitive-improvement use while retaining the major depressive disorder indication. The product launches for depression but not for the patented cognitive method.

This can still create indirect exposure if physicians routinely prescribe the generic for cognitive symptoms or if marketing materials promote cognitive benefits.

Scenario 3: Delayed launch under settlement

The applicant accepts a future entry date. The settlement may permit launch before the estimated 2032 patent expiration but after expiration of earlier patents or regulatory exclusivity.

This scenario can produce generic competition for depression while preserving some residual method-of-use protection.

What geographic coverage does Patent 9,125,909 provide?

US Patent 9,125,909 provides protection only in the United States. Related applications or counterpart patents may exist in Europe, Canada, Japan, and other jurisdictions, but each jurisdiction applies its own:

• Claim construction rules.
• Patent-term rules.
• Patentability standards.
• Supplementary protection certificate or pediatric-extension rules.
• Generic approval and labeling rules.

A US Paragraph IV certification has no direct legal effect outside the United States. Geographic freedom-to-operate analysis must review the corresponding national patent families and local prosecution and litigation records.

What manufacturing and intellectual-property barriers remain?

The most important manufacturing barrier is not the wet-granulation limitation alone. It is the combination of:

• Vortioxetine hydrobromide selection.
• Crystalline solid-state form.
• Tablet composition.
• Excipients and concentration ranges.
• Process controls.
• Finished-product equivalence.

A generic manufacturer can potentially reduce risk by using a different salt, different solid-state form, different excipients, or a different manufacturing process. Each modification may create separate regulatory, stability, bioequivalence, or commercial problems.

The patent therefore creates a higher barrier for a generic seeking to reproduce the branded tablet precisely than for a generic developing a nonidentical formulation. Its strongest commercial function is likely to preserve leverage in ANDA litigation and settlement negotiations rather than to block every possible vortioxetine product through 2032.

Key Takeaways

• US Patent 9,125,909 covers crystalline vortioxetine or a pharmaceutically acceptable salt for treating cognitive impairment in a patient diagnosed with depression.
• Claim 1 is the central protection and covers decline in processing speed, executive function, attention, or verbal learning and memory.
• Claim 3 specifically targets vortioxetine hydrobromide.
• Claims 4 through 6 cover a wet-granulated tablet and a defined excipient system.
• Claims 7 through 11 narrow the invention to specific depressive conditions, including major depressive disorder and treatment-resistant depression.
• The patent is expected to expire in approximately 2032 based on its 2011 priority history, subject to the official USPTO calculation.
• FDA approved vortioxetine for major depressive disorder, not as a broad cognitive-impairment therapy.
• Generic risk depends on Orange Book listing, use-code scope, Paragraph IV certifications, label carve-outs, and induced-infringement evidence.
• The patent does not create biosimilar risk because vortioxetine is a small-molecule drug.
• Claims 1 and 3 have the greatest commercial significance; the formulation claims are narrower and more design-around sensitive.

FAQs About US Patent 9,125,909 and Vortioxetine

Does Patent 9,125,909 cover all uses of Trintellix?

No. It covers a specific cognitive-impairment treatment method in depressed patients using crystalline vortioxetine or a salt. It does not broadly cover every use of Trintellix for major depressive disorder.

Is vortioxetine hydrobromide specifically protected?

Yes. Claim 3 specifically recites 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide. The independent claim also encompasses pharmaceutically acceptable salts in crystalline form.

Can a generic launch for depression without a cognitive indication?

Potentially. A generic applicant may pursue a label carve-out if the relevant FDA use code and labeling structure permit removal of the patented cognitive use. The applicant would still face risk if its label or marketing induces the patented use.

Does the patent cover the exact Trintellix tablet?

Claims 4 through 6 may cover a tablet using the recited excipients, wet granulation, and percentage ranges. The patent does not necessarily cover every Trintellix tablet or every vortioxetine tablet under those claims.

Is Patent 9,125,909 a biologic or biosimilar barrier?

No. Vortioxetine is a small-molecule active ingredient. Competition proceeds through the ANDA pathway, not the biosimilar pathway.

References

1. U.S. Patent No. 9,125,909. (2015). Methods of treating cognitive impairment. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2013). Trintellix (vortioxetine) prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.

4. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations, patent and exclusivity information. FDA.

5. United States Patent and Trademark Office. (2024). Patent term calculator. USPTO.

6. Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).

7. Hatch-Waxman Amendments, 35 U.S.C. §§ 271(e), 282, 283, and 284.

Drugs Protected by US Patent 9,125,909

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					Y
Takeda Pharms Usa	TRINTELLIX	vortioxetine hydrobromide	TABLET;ORAL	204447-002	Sep 30, 2013		RX	Yes	No					Y
Takeda Pharms Usa	TRINTELLIX	vortioxetine hydrobromide	TABLET;ORAL	204447-003	Sep 30, 2013		DISCN	Yes	No					Y

Foreign Priority and PCT Information for Patent: 9,125,909

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Denmark	2006 00824	Jun 16, 2006
Denmark	2006 01223	Sep 22, 2006
Denmark	2006 01384	Oct 25, 2006

International Family Members for US Patent 9,125,909

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	061481
Argentina	065797
Austria	E495745