United States Patent 7,144,884: Claim Scope, Vortioxetine Coverage, Expiration and Patent Landscape
United States Patent No. 7,144,884 is the core composition-of-matter patent covering vortioxetine, also known as 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine. The patent was assigned to H. Lundbeck A/S and covers a broad family of substituted diaryl sulfide piperazines, specific chemical species, pharmaceutical compositions, and methods for treating affective disorders. Its listed patent term, including the applicable patent-term extension, ended June 21, 2022. The patent no longer creates a current U.S. patent barrier to generic vortioxetine, although follow-on patents and settlement terms historically affected launch timing.[1-4]
What drug and chemical class does U.S. Patent 7,144,884 protect?
The patent protects substituted aryl sulfanyl piperazines. The central structure contains:
- A piperazine ring;
- An aryl group attached to the piperazine nitrogen;
- A sulfur atom linking that aryl group to a second substituted aryl group;
- Optional alkyl substituents on the piperazine ring;
- Optional halogen, alkyl, alkoxy, trifluoromethyl, hydroxy, cyano, nitro, amino and related substituents.
The commercially important compound is vortioxetine, formerly associated with the development code Lu AA21004. Its chemical identity is commonly stated as 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine. The patent covers vortioxetine as a free compound and as a pharmaceutically acceptable acid-addition salt, including the hydrobromide salt used in the marketed product Trintellix.[1,5]
What is the patent’s ownership and prosecution profile?
| Item |
Information |
| Patent |
U.S. Patent No. 7,144,884 |
| Title |
Novel compounds |
| Original assignee |
H. Lundbeck A/S |
| Important commercial compound |
Vortioxetine |
| U.S. filing family |
Priority dating to 2000; U.S. nonprovisional filing in 2001 |
| Publication |
U.S. Patent Application Publication issued before grant |
| Grant date |
December 5, 2006 |
| Patent term basis |
20-year term from the relevant U.S. nonprovisional filing date |
| Listed expiration |
June 21, 2022, including patent-term extension |
| Product association |
Trintellix, formerly Brintellix in certain markets |
| FDA application |
NDA 204447 |
| Current status |
Expired |
The expiration date is the commercially relevant date reflected in FDA and patent records. The patent-term extension was tied to the regulatory approval of vortioxetine and extended the base term beyond the ordinary 20-year expiration date.[1,2]
How broad is claim 1 of U.S. Patent 7,144,884?
Claim 1 is a genus claim directed to a defined family of compounds represented by the patent’s general formula I. In the supplied claim text, the operative limitations include:
- p is 0, 1, 2, 3 or 4;
- q is 0, 1 or 2;
- s is 2;
- R1 is independently C1-C6 alkyl;
- R2 and R3 can be selected from numerous substituent classes;
- the compound can be present as a pharmaceutically acceptable acid-addition salt.
The claim therefore does not cover every aryl piperazine or every diaryl sulfide. It covers compounds that satisfy the particular substitution pattern, ring-count limitations and sulfur-linked architecture defined by formula I.
What structural features are required?
The most important restrictions are:
- The claimed compound must have the specific formula I architecture.
- The sulfur-linked aryl system must satisfy the p, q and s limitations.
- The permitted substituents are closed by the enumerated chemical classes.
- The claim reaches acid-addition salts of otherwise covered compounds.
- The claim is limited to compounds, rather than methods, compositions or manufacturing processes.
The substituent language is chemically broad. It reaches alkyl, alkenyl, alkynyl, halo, cyano, nitro, hydroxy, cycloalkyl, acyl, sulfonyl, amino and aryl substituents, subject to the stated carbon-number and connectivity restrictions.
The claim text supplied by the user contains apparent transcription defects, including mismatched brackets and an occurrence of "C16-alk(en/yn)yl." The analysis above treats these as typographical errors and relies on the issued-claim framework rather than extending claim scope from a defective transcription.
Does claim 1 cover vortioxetine?
Yes. Vortioxetine is expressly listed in claim 5 and separately claimed in dependent claim 17.
Claim 5 identifies 17 specific compounds. The commercially relevant entry is:
1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine
Claim 17 narrows claim 5 to that compound and its pharmaceutically acceptable acid-addition salts. This is stronger than relying solely on the broad genus in claim 1 because the marketed active ingredient is individually recited.
What other compounds are expressly listed?
The specifically listed compounds include analogs containing:
- Trifluoromethyl;
- Bromine;
- Methylsulfanyl;
- Hydroxy;
- Dimethyl substitution in several positional arrangements;
- Chlorine;
- Methoxy;
- Fluorine;
- Methyl-substituted piperazine rings.
The list includes both phenyl-substituted piperazines and methyl- or dimethyl-substituted piperazine analogs. Claims 13 through 29 separately claim each listed species.
What do claims 2 through 6 cover?
Claims 2 through 6 create progressively narrower compound and composition protection.
| Claim |
Subject matter |
Commercial significance |
| 2 |
Claim 1 compounds with p limited to 0, 1 or 2 |
Narrows the aryl substitution pattern |
| 3 |
Claim 1 compounds where R2 is trifluoromethyl or C1-C6 alkyl |
Captures important substitution classes |
| 4 |
Claim 1 compounds with defined halogen, alkoxy, alkylsulfanyl, alkyl, hydroxy or trifluoromethyl R3 groups |
Narrows the second aryl ring |
| 5 |
Markush-independent list of 17 named compounds |
Provides direct species coverage |
| 6 |
Pharmaceutical composition containing a claim 1 compound or salt and a carrier or diluent |
Covers dosage-form compositions containing covered compounds |
Claim 6 is not limited to tablets, capsules or any particular excipient. Its breadth depends on whether the composition contains a compound falling within claim 1. The claim does not independently require vortioxetine, a particular dose, a particular salt, a release profile or a particular formulation technology.
What do method-of-use claims 7 through 12 cover?
Claims 7 through 12 cover treatment of affective disorders using a broader compound genus than claims 1 through 6.
Claim 7 includes compounds in which:
- X is O or S;
- p may range from 0 to 8;
- q may range from 0 to 4;
- s may range from 0 to 5;
- R2 and R3 include extensive substituent classes.
The method claim therefore extends beyond the sulfur-linked, s=2 compound family of claim 1. It reaches both oxygen and sulfur analogs and permits wider positional substitution.
Which diseases are expressly covered?
Claim 9 identifies:
- Depression;
- Anxiety disorder;
- Obsessive-compulsive disorder.
Claim 10 narrows anxiety disorder to:
- General anxiety disorder;
- Panic disorder.
Claim 8 specifies that the treated living animal body is a human. Claim 11 narrows the broader method genus into another defined compound group, and claim 12 identifies the same named compounds listed in claim 5 as treatment agents.
How do the method claims differ from the compound claims?
The compound claims are product claims. They can be implicated by making, using, selling, offering to sell or importing a covered compound during the patent term.
The method claims require performance of a claimed therapeutic method. They are relevant to administering a covered compound for a covered indication. A generic applicant could seek to avoid an indication-specific method claim through a section viii carve-out if the FDA-approved labeling excludes the patented use. That strategy does not avoid an active composition-of-matter claim.
Because 7,144,884 has expired, these distinctions now have historical rather than prospective blocking significance in the United States.
What is the patent strength of U.S. Patent 7,144,884?
The patent had high historical strength against products containing vortioxetine because the active compound was individually claimed.
Strength by claim category
| Claim category |
Historical strength |
Reason |
| Claim 17, vortioxetine species |
High |
Directly names the commercial compound |
| Claim 5, listed species |
High |
Provides express species coverage |
| Claim 1, genus |
Moderate to high |
Broad chemical genus, subject to construction and validity challenges |
| Claim 6, composition |
Moderate |
Requires a covered compound plus carrier or diluent |
| Claims 7-12, methods |
Moderate |
Broader genus but dependent on treatment conduct and indication |
| Claims 13-29 |
High |
Individual species claims |
The principal validity pressure points for a genus claim of this type would have been anticipation, obviousness, written description, enablement and claim construction. The named-species claims would generally have been more commercially valuable because they reduce disputes over whether the marketed molecule falls within the disclosure and claim boundaries.
What does the patent not protect?
The patent does not, based on the supplied claims, independently claim:
- A specific crystalline polymorph;
- A specific particle-size distribution;
- A particular tablet coating;
- A controlled-release formulation;
- A specific dosage strength;
- A manufacturing process;
- A synthetic intermediate;
- A process impurity specification;
- A particular salt other than through the generic acid-addition-salt language;
- A combination therapy;
- A pharmacokinetic dosing regimen.
Those areas could be covered by separate patents.
What patents protect Trintellix beyond U.S. Patent 7,144,884?
The core U.S. product patent was accompanied by later patent activity associated with vortioxetine and Trintellix. FDA Orange Book records historically identified U.S. Patent Nos. 7,144,884 and 8,476,297 in connection with Trintellix.[2]
| Patent |
General role in the Trintellix estate |
Status relevance |
| 7,144,884 |
Core compound, salt, composition and treatment claims |
Expired June 21, 2022 |
| 8,476,297 |
Follow-on vortioxetine patent listed in the FDA product record |
Required separate claim and expiration analysis |
| Other family or foreign rights |
Potential formulation, process or jurisdiction-specific coverage |
Must be reviewed by jurisdiction and claim set |
The existence of a later patent does not extend the term of the 7,144,884 compound claims. Each patent has its own filing history, claim scope, term, terminal disclaimer status and Orange Book listing.
When did vortioxetine lose U.S. exclusivity?
Vortioxetine lost the principal composition-of-matter patent barrier on June 21, 2022. FDA approval occurred on September 30, 2013, under NDA 204447.[2,5]
Key exclusivity timeline
| Date |
Event |
| June 21, 2000 |
Earliest relevant priority period for the patent family |
| June 21, 2001 |
U.S. nonprovisional filing period |
| December 5, 2006 |
U.S. Patent 7,144,884 issued |
| September 30, 2013 |
FDA approved vortioxetine for major depressive disorder |
| 2018 |
Ordinary five-year new chemical entity exclusivity period ended |
| 2019 |
Any applicable pediatric-exclusivity period would have ended after the FDA-approved pediatric extension period |
| June 21, 2022 |
Listed expiration of U.S. Patent 7,144,884 |
| After June 2022 |
Generic launch activity became legally possible, subject to other patents and settlements |
FDA regulatory exclusivity and patent exclusivity are separate. The five-year NCE period prevented certain ANDA approvals, while the patent controlled infringement and launch risk. Neither regulatory exclusivity nor the 7,144,884 patent remains a current U.S. barrier.
Which companies challenged the vortioxetine patents?
Generic-drug companies challenged Trintellix patents through ANDA Paragraph IV certifications. Public reporting and patent-litigation records identify challenges involving multiple generic manufacturers, including Amneal, Apotex, Aurobindo, Dr. Reddy's, Lupin and Zydus entities. The exact defendant group, asserted patent claims and disposition varied by case and settlement.[3,4]
Paragraph IV litigation is significant because an ANDA filer can trigger a 30-month FDA approval stay by notifying the NDA holder and patent owner that a listed patent is invalid, unenforceable or not infringed. The stay does not itself determine validity. It delays approval while the litigation proceeds, subject to statutory exceptions.[6]
What was the commercial effect of the challenges?
The challenges created launch uncertainty before June 2022. The relevant issues included:
- Whether the generic product contained the same vortioxetine active ingredient;
- Whether the proposed product infringed the compound or salt claims;
- Whether later-listed formulation claims remained enforceable;
- Whether settlements permitted an agreed launch date;
- Whether the applicant could use a section viii statement for method-of-use claims;
- Whether a court invalidated or declined to enforce asserted claims.
After the core patent expired, generic entry became substantially less constrained. Follow-on patents could still affect formulation-specific products, but they did not recreate the expired compound patent.
What is the Orange Book status of U.S. Patent 7,144,884?
The patent was historically listed in the FDA Orange Book for the approved vortioxetine product. Its Orange Book significance ended when the patent expired on June 21, 2022.[2]
Orange Book listing is not a finding that every listed claim is valid or infringed. It is an FDA administrative listing connected to the approved drug and patent information submitted by the NDA holder. Patent disputes remain matters for the courts.
A generic applicant could address the listing through:
- Paragraph III certification, accepting approval after patent expiration;
- Paragraph IV certification, challenging validity, enforceability or infringement;
- Section viii statement, carving out a patented method of use;
- A combination of certifications for different listed patents.
What generic launch risks existed for vortioxetine?
Before June 21, 2022, the largest risk was infringement of the express vortioxetine species claim. A generic containing the same active ingredient would have faced a direct product-claim issue unless it prevailed on validity, noninfringement or enforceability.
The risk profile after that date changed:
| Risk |
Pre-expiration |
Post-expiration |
| Infringement of vortioxetine species claim |
High |
None for future U.S. activity under the expired patent |
| Infringement of broad genus claim |
Material |
None under the expired patent |
| Method-of-use claim exposure |
Material for labeled indications |
None under the expired patent |
| Formulation patent exposure |
Potentially material |
Dependent on separate patent status |
| Salt or solid-form claim exposure |
Product-specific |
Dependent on separate patent status |
| Manufacturing-process exposure |
Possible only under separate claims |
Dependent on separate patent status |
The generic product still had to satisfy FDA ANDA requirements for pharmaceutical equivalence, bioequivalence, manufacturing quality and labeling. Patent expiration did not eliminate regulatory requirements.
How does the 7,144,884 patent compare with formulation and method patents?
The 7,144,884 patent is materially stronger than a typical formulation patent against a generic active-ingredient product because it claims the active compound itself.
| Protection type |
What it covers |
Typical design-around potential |
| Composition of matter |
Vortioxetine and related molecules |
Very limited before expiration |
| Salt claim |
Acid-addition salts of covered molecules |
Potentially dependent on claim language |
| Pharmaceutical composition |
Covered compound with carrier or diluent |
Moderate, but difficult if active ingredient is covered |
| Method of treatment |
Administration for specified disorders |
Label and indication dependent |
| Formulation |
Excipient, release, dosage-form or stability configuration |
Greater design-around potential |
| Manufacturing process |
Synthetic route or purification method |
Alternative process may avoid infringement |
| Solid form |
Crystal form, hydrate or polymorph |
Depends on physical-form claim scope |
For investors and licensors, the core 7,144,884 asset should be treated as an expired foundational right. Its historical value came from preventing substitution of the active ingredient itself, not from a narrow formulation monopoly.
What licensing and settlement issues affected the patent estate?
H. Lundbeck developed vortioxetine and partnered with Takeda for commercialization in the United States and other markets. Takeda marketed the U.S. product as Trintellix.[5]
Generic settlements involving the Trintellix patent estate could establish an authorized or agreed launch date before the latest listed patent expiration. Settlement terms are often confidential or only partially disclosed through court filings and regulatory documents. A settlement does not establish that the asserted patents were valid or infringed.
The relevant diligence distinction is:
- Commercial licensing determines which company can market the product.
- Patent ownership determines who controls enforcement.
- Settlement agreements determine whether a particular ANDA filer receives an earlier launch right.
- FDA approval determines when the generic may legally be marketed under the ANDA.
What is the geographic coverage of U.S. Patent 7,144,884?
The patent provided rights only in the United States. Foreign equivalents required separate national or regional prosecution and could have different:
- Claim scope;
- Priority dates;
- Patent-term adjustments;
- Supplementary protection certificates;
- Opposition histories;
- Expiration dates;
- Litigation outcomes.
Expiration of U.S. Patent 7,144,884 did not terminate foreign rights. A global freedom-to-operate analysis therefore requires review of the European, Canadian, Japanese, Australian and other national family members.
Key Takeaways
- U.S. Patent 7,144,884 is the foundational vortioxetine patent.
- Vortioxetine is expressly claimed as 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine and its pharmaceutically acceptable acid-addition salts.
- The patent includes broad compound-genus claims, named-species claims, pharmaceutical-composition claims and affective-disorder treatment claims.
- The strongest historical claims were claims 17 and 29-series species claims covering individually identified compounds.
- The patent’s listed U.S. expiration date was June 21, 2022.
- FDA approval for vortioxetine occurred on September 30, 2013, under NDA 204447.
- Generic companies pursued Paragraph IV challenges involving the Trintellix patent estate.
- The patent does not independently claim a specific polymorph, dosage strength, formulation technology or manufacturing route.
- Later patents, including U.S. Patent No. 8,476,297, required separate assessment and did not extend the expired term of 7,144,884.
- Current U.S. competitive risk is driven by generic vortioxetine availability and any surviving follow-on formulation, solid-form or process rights, not by 7,144,884.
FAQs About U.S. Patent 7,144,884
Is vortioxetine explicitly named in U.S. Patent 7,144,884?
Yes. The compound corresponding to vortioxetine is listed among the specific compounds in claim 5 and is separately claimed in claim 17.
Did U.S. Patent 7,144,884 cover Trintellix tablets?
It covered vortioxetine and pharmaceutical compositions containing covered compounds. It did not, based on the supplied claims, require the specific Trintellix tablet formulation, strength or coating.
Could a generic avoid U.S. Patent 7,144,884 by using a different salt?
Not reliably before expiration. The claims cover pharmaceutically acceptable acid-addition salts, and vortioxetine itself was separately claimed. A different salt would have required claim-specific analysis.
Did the patent cover vortioxetine for anxiety or obsessive-compulsive disorder?
The method claims identify depression, anxiety disorder and obsessive-compulsive disorder, including generalized anxiety disorder and panic disorder. Those method claims expired with the patent.
Is U.S. Patent 7,144,884 still relevant to a new vortioxetine product?
It remains relevant as historical patent and prosecution evidence, but it no longer blocks new U.S. activities because the patent expired. Current risk must be assessed against separate unexpired patents and FDA requirements.
References
-
United States Patent and Trademark Office. (2006). U.S. Patent No. 7,144,884, Novel compounds. U.S. Department of Commerce.
-
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
-
CourtListener. (n.d.). Patent litigation records concerning vortioxetine and Trintellix. Free Law Project.
-
United States District Court for the District of Delaware. (n.d.). Vortioxetine patent litigation docket materials. U.S. District Court.
-
U.S. Food and Drug Administration. (2013). Trintellix prescribing information, NDA 204447. FDA.
-
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Patent and exclusivity information. FDA.
