Details for Patent: 5,827,871

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Summary for Patent: 5,827,871

Title:	Medicaments 1,2,3,4-tetrahydrocarbazoles and 5-HT1 agonist use thereof
Abstract:	Use of a compound of general formula (I): Formula (I) wherein R1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, arylC1-6alkoxy, -CO2R4, -(CH2)nCN, -(CH2)nCONR5R6, -(CH2)nSO2NR5R6, C1-6alkanoylamino(CH2)n, or C1-6alkylsulphonylamino(CH2)n; R4 represents hydrogen, C1-6alkyl or arylC1-6alkyl; R5 and R6 each independently represent hydrogen or C1-6alkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a ring; n represents 0, 1 or 2; and R2 and R3 each independently represent hydrogen, C1-6alkyl or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt thereof, in the manufacture of a medicament for the treatment of a condition where a 5-HT1-like agonist is indicated, for example migraine. Novel compounds of formula (I), processes for preparing them and pharmaceutical compositions containing them are also described.
Inventor(s):	Francis David King, Laramie Mary Gaster, Alberto Julio Kaumann, Rodney Christopher Young
Assignee:	Endo Pharmaceuticals Inc
Application Number:	US08/442,720
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 5,827,871: Scope, Claims, Expiration, and 5-HT1 Agonist Patent Landscape

U.S. Patent 5,827,871 protects substituted 3-amino-1,2,3,4-tetrahydrocarbazoles, their physiologically acceptable salts, solvates and hydrates, pharmaceutical compositions containing them, and methods of treating conditions, particularly migraine, for which a 5-HT1-like agonist is indicated. The patent issued on October 27, 1998, and its enforceable U.S. term has expired under the ordinary 20-year patent-term rule. The patent does not appear to protect a currently marketed FDA-approved drug or create an active Orange Book barrier.

The central commercial subject matter is 3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole and related 6-substituted analogues. The claims combine broad genus protection with narrower species claims directed to cyano, sulfonamide, nitro, carboxamide, carboxamidomethyl, carboxamidoethyl, and enantiomeric compounds.

What does U.S. Patent 5,827,871 cover?

The patent covers three principal categories:

Claim category	Claims	Covered subject matter
Therapeutic methods	1-7	Administration of formula I compounds to treat conditions responsive to a 5-HT1-like agonist, including migraine
Chemical compounds	8-16	Formula IA compounds, named species, stereoisomers, and specified salts
Pharmaceutical composition	17	A claimed compound with a physiologically acceptable carrier

The core scaffold is a 3-amino-1,2,3,4-tetrahydrocarbazole. The structure contains:

• An amino substituent at the 3-position.
• A variable substituent, R1, on the fused aromatic ring.
• Variable substitution at the amino group through R2 and R3.
• Optional physiologically acceptable salts, solvates and hydrates.

The patent is therefore a small-molecule medicinal-chemistry patent rather than a formulation-only patent or manufacturing-process patent.

How broad is the genus in claim 1?

Claim 1 is a broad method-of-treatment claim. It covers administering an effective amount of any compound within the defined formula I genus for a condition in which a 5-HT1-like agonist is indicated.

The R1 group includes:

• Hydrogen
• Halogen
• Trifluoromethyl
• Nitro
• Hydroxy
• C1-6 alkyl
• C1-6 alkoxy
• Aryl-C1-6 alkoxy
• Carboxylate
• Cyanoalkyl
• Carboxamidoalkyl
• Sulfonamidoalkyl
• Alkanoylaminoalkyl
• Alkylsulfonylaminoalkyl

R2 and R3 may independently be hydrogen, C1-6 alkyl or benzyl. Alternatively, they may form a pyrrolidino, piperidino or hexahydroazepino ring with the nitrogen atom.

The breadth of claim 1 is materially greater than the narrower compound claims. A compound could fall within the method claim even if it is not one of the specifically named compounds in claims 11-15, provided that:

1. It satisfies the structural limitations of formula I.
2. It is administered to a subject.
3. The amount is therapeutically effective.
4. The indication is one for which a 5-HT1-like agonist is indicated.

The claim does not require migraine. Migraine is separately recited in claim 2.

What compounds are specifically protected?

Claims 11-15 identify specific tetrahydrocarbazole species. The named compounds include:

Claim	Compound class
11	6-cyano, N-methylsulfonamidomethyl, sulfonamido, nitro, piperidinylcarbonyl, pyrrolidinylcarbonyl and methanesulfonamido derivatives
12	6-(N-methylcarboxamido), 6-(N,N-dimethylcarboxamido) and 6-(N,N-diethylcarboxamido) derivatives
13	6-carboxamidomethyl and 6-(2-carboxamidoethyl) derivatives
14	(+)-3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole
15	(-)-3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole

The most commercially relevant species is likely the enantiomerically defined 3-amino-6-carboxamido-1,2,3,4-tetrahydrocarbazole covered by claims 14 and 15. The claims do not identify a generic drug name, dosage form, strength, route of administration or marketed product.

Claims 8-10 provide intermediate compound protection for formula IA. They narrow R1 to selected electron-withdrawing and carboxamide-related substituents. Claim 9 narrows the carboxamide substituent to a directly attached carboxamide, because n is zero. Claim 10 further limits R5 and R6 to hydrogen or methyl.

What is the scope of claims 2 through 7?

Claims 2-7 progressively narrow the broad therapeutic method:

Claim	Limitation
2	Treatment of migraine
3	Selected R1 groups, including halogen, CF3, alkoxy, cyanoalkyl, carboxamidoalkyl and sulfonamide groups
4	Direct carboxamide substitution, with R5/R6 as hydrogen, methyl, ethyl or propyl; R2/R3 as hydrogen, methyl or ethyl
5	Same compound limitations as claim 4, specifically for migraine
6	R5 and R6 limited to hydrogen or methyl
7	Same limitation as claim 6, specifically for migraine

Claims 5 and 7 are the narrowest migraine method claims. They require:

• A tetrahydrocarbazole with a directly attached carboxamide.
• A carboxamide substituted with hydrogen or methyl groups.
• R2 and R3 independently selected from hydrogen, methyl or ethyl.
• Treatment of migraine.

These limitations would reduce the number of potentially infringing compounds but could improve validity against prior art directed to broader 5-HT1 agonist classes.

What formulation patents are protected by U.S. Patent 5,827,871?

The patent does not claim a specific formulation technology. Claim 17 covers a pharmaceutical composition comprising a formula I compound and a physiologically acceptable carrier.

That language can reach conventional dosage forms, including tablets, capsules, solutions or suspensions, if they contain a claimed compound. It does not expressly require:

• A particular excipient.
• A controlled-release matrix.
• A transdermal system.
• A nasal delivery device.
• A particular particle size.
• A specific bioavailability profile.
• A defined dose or concentration.
• A specific manufacturing process.

Claim 17 is therefore composition-by-presence protection. It is weaker than a detailed formulation claim when the active compound is no longer protected, particularly where the product contains an unclaimed active ingredient or a structurally different analogue.

Does the patent protect a method of use for migraine?

Yes. Claim 2 covers treatment of migraine using a formula I compound. Claims 5 and 7 provide narrower migraine claims focused on carboxamide-substituted tetrahydrocarbazoles.

The method claims raise the standard infringement questions applicable to therapeutic-use claims:

• Whether the accused product contains a compound within the claimed structural genus.
• Whether the product is indicated, labeled or promoted for migraine or another covered condition.
• Whether administration is to a subject in need of treatment.
• Whether the administered amount is effective.
• Whether the relevant activity is a 5-HT1-like agonist activity.

A product with an overlapping structure but a non-migraine label could still present risk under claim 1 if the product is used for another condition in which a 5-HT1-like agonist is indicated. Direct infringement would generally depend on the actual use and induced-infringement evidence, not structural identity alone.

When did U.S. Patent 5,827,871 lose exclusivity?

The patent issued on October 27, 1998. Under the modern U.S. patent-term rule, a utility patent generally expires 20 years from the earliest effective U.S. nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers. The patent's ordinary term therefore would have ended approximately two decades after its underlying U.S. filing date, in the mid-2010s.

Event	Date or status
U.S. patent number	5,827,871
Issue date	October 27, 1998
Patent type	Utility patent
Subject matter	5-HT1-like agonist tetrahydrocarbazoles
Ordinary U.S. expiration	Approximately mid-2010s, based on the statutory 20-year term
Current enforceability	Expired
Patent-term extension relevance	No identified active extension associated with this patent
Current Orange Book barrier	No identified listed product or active patent barrier

The precise expiration date must be determined from the patent's earliest effective U.S. nonprovisional filing date, any patent-term adjustment, and the official USPTO maintenance and term records. On the available patent chronology, the patent is no longer enforceable.

Is U.S. Patent 5,827,871 listed in the FDA Orange Book?

No active Orange Book listing has been identified for U.S. Patent 5,827,871. The patent does not appear to be associated with a currently marketed FDA-approved product containing the claimed tetrahydrocarbazole active ingredient.

The Orange Book lists patents submitted by sponsors for approved drug products under FDA's patent-listing framework. A patent can be scientifically relevant to a drug candidate without being listed in the Orange Book. Listing requires an approved product and a patent that meets the statutory and regulatory listing criteria.

For this patent, the commercial implications are:

• No current Orange Book patent-expiration date is expected to delay an abbreviated new drug application.
• A generic applicant would not ordinarily face a Paragraph IV certification directed to this expired patent.
• The patent cannot create a current automatic 30-month stay under Hatch-Waxman.
• Any residual relevance would be historical, contractual or related to a separate patent family.

Were Paragraph IV challenges filed against this patent?

No meaningful Paragraph IV challenge has been identified against U.S. Patent 5,827,871. The principal reason is that Paragraph IV litigation is tied to patents listed for an approved reference listed drug. The patent appears to have no current Orange Book role and no associated marketed product requiring an ANDA certification.

A Paragraph IV challenge would have been commercially plausible only if:

1. A formula I compound had been approved as an NDA product.
2. The patent had been listed against that product.
3. The patent remained unexpired when an ANDA was submitted.

Those conditions do not appear to apply.

What is the patent landscape around 5-HT1 agonists?

U.S. Patent 5,827,871 sits within the broader triptan and serotonin-receptor agonist landscape. Relevant commercial competitors include sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan and eletriptan. These compounds are chemically distinct from the tetrahydrocarbazole genus claimed here.

Drug or class	Representative structure	Primary target profile	Relationship to Patent 5,827,871
Sumatriptan	Indole sulfonamide	5-HT1B/1D agonist	Structurally distinct
Naratriptan	Substituted piperidine-indole	5-HT1B/1D agonist	Structurally distinct
Zolmitriptan	Oxazolidinone-containing indole	5-HT1B/1D agonist	Structurally distinct
Rizatriptan	Indole ethylamine	5-HT1B/1D agonist	Structurally distinct
Almotriptan	Pyrrolidine-substituted indole	5-HT1B/1D agonist	Structurally distinct
Eletriptan	Pyrrolidine-substituted indole	5-HT1B/1D agonist	Structurally distinct
Patent 5,827,871 compounds	3-amino-tetrahydrocarbazoles	5-HT1-like agonist activity	Directly covered where structure and use meet

The patent's competitive position was strongest as a discovery-stage composition patent. It does not dominate the entire 5-HT1 agonist field. It covers a particular fused-ring chemical genus and therapeutic use, while established triptans occupy separate chemical and patent estates.

How strong is the patent estate?

Structural strength

The compound claims are potentially strong against exact copies of the named species and close analogues that fall within formula IA. Claims 14 and 15 are particularly specific because they identify the positive and negative enantiomers of the 6-carboxamido compound.

The broader Markush claims are more exposed to:

• Anticipation by earlier tetrahydrocarbazole disclosures.
• Obviousness combinations involving known 5-HT1 agonists and substituted carbazole chemistry.
• Written-description challenges to the full breadth of the R1/R2/R3 combinations.
• Enablement challenges if the genus covers compounds with materially different pharmacology or synthesis.
• Claim-construction disputes involving ambiguous substituent nomenclature.

Method-claim strength

The method claims depend on both structural coverage and therapeutic use. They may be harder to enforce than a pure composition claim because the patent holder must establish the relevant administration and indication. Claims 2, 5 and 7 are narrower but more commercially focused because migraine is a defined therapeutic indication.

Composition-claim strength

Claim 17 is useful when the composition contains a claimed active compound. It does not independently create a substantial barrier around conventional excipients, dosage forms or delivery technologies.

Term strength

The patent's term is the principal weakness. Because the U.S. patent has expired, its former validity and scope have little current blocking value unless a separate continuation, divisional, reissue or related patent remained active.

Are biosimilar risks relevant?

No. Biosimilar regulation applies to biological products. The claimed compounds are chemically synthesized small molecules. The relevant follow-on pathway would be an ANDA for a generic drug, or an NDA under a different statutory pathway for a new product, not a 351(k) biosimilar application.

Any current competitive risk would therefore involve:

• Generic small-molecule development.
• New chemical entities with similar receptor pharmacology.
• Reformulations or alternative delivery systems.
• Products using different active structures but competing for the same migraine market.

What manufacturing and intellectual-property barriers exist?

Patent 5,827,871 does not appear, from the supplied claims, to claim a manufacturing process. It claims compounds, treatment methods and a composition.

Potential manufacturing barriers would instead arise from:

• Difficult preparation of the tetrahydrocarbazole core.
• Enantiomeric separation or asymmetric synthesis.
• Control of regioisomer formation at the 6-position.
• Salt selection and solid-state characterization.
• Purification of the 3-amino stereoisomers.
• Process patents in related family members.
• Know-how covering scale-up, impurity control and crystallization.

These barriers are distinct from the expired compound claims. A competitor could avoid the patent while still facing process-development costs or separate active patents owned by other parties.

What licensing or settlement deals are associated with the patent?

No licensing transaction or litigation settlement specifically tied to U.S. Patent 5,827,871 has been identified. The patent record supplied does not establish an assignment, license, covenant not to sue or settlement affecting current rights.

Any historical license involving the patent would need to be distinguished from:

• A license to a broader 5-HT1 agonist platform.
• A license covering a different triptan.
• A territorial license.
• A process or formulation license.
• A settlement involving a related patent rather than Patent 5,827,871 itself.

Because the patent is expired, a historical license would have limited current exclusionary value unless it contained surviving royalty, confidentiality or non-compete obligations.

What generic launch scenarios exist?

The patent itself does not prevent a current generic launch because its U.S. term has expired and no active Orange Book listing has been identified.

Scenario	Patent 5,827,871 impact
Generic copies a named compound	No current U.S. patent blocking effect from this patent
Generic uses a close formula I analogue	No current infringement exposure from the expired patent
Generic markets a conventional tablet	Claim 17 no longer blocks the product
Product is labeled for migraine	Claims 2, 5 and 7 are expired and do not create a current barrier
Product uses a different active ingredient	Outside the patent's compound claims
Product relies on a later formulation or process patent	Risk depends on separate, active patents

The principal diligence issue is therefore not this patent's expired claims, but whether related patents cover a specific active ingredient, polymorph, salt, formulation, manufacturing process or approved method of use.

What geographic coverage does the patent provide?

U.S. Patent 5,827,871 provides territorial rights only in the United States. Corresponding foreign rights would depend on separately issued national patents or regional patents derived from the same priority filing.

The U.S. patent cannot independently block:

• Manufacture wholly outside the United States.
• Sale outside the United States.
• Use outside the United States.
• Importation into the United States if no enforceable U.S. patent remains.

A global freedom-to-operate review would need to examine the corresponding European, Japanese, Canadian, Australian and other national family members, together with their individual expiration and maintenance status.

Key Takeaways

• U.S. Patent 5,827,871 covers 3-amino-1,2,3,4-tetrahydrocarbazole 5-HT1-like agonists.
• Claims 1-7 protect therapeutic use, with migraine expressly covered by claims 2, 5 and 7.
• Claims 8-16 protect chemical compounds, including named species and positive and negative enantiomers.
• Claim 17 covers pharmaceutical compositions containing a claimed compound and a physiologically acceptable carrier.
• The patent does not claim a specific extended-release, nasal, transdermal or other delivery technology.
• The patent issued on October 27, 1998 and has expired under the ordinary U.S. patent-term framework.
• No current Orange Book listing, Paragraph IV dispute, active biosimilar issue or identified settlement has been associated with the patent.
• The patent does not dominate competing triptans such as sumatriptan, rizatriptan, zolmitriptan, naratriptan, almotriptan or eletriptan.
• Current diligence should focus on related continuation and foreign patents, active formulation or process patents, and any later patents covering a commercial product.

FAQs About U.S. Patent 5,827,871

Does U.S. Patent 5,827,871 cover sumatriptan?

No. Sumatriptan is structurally distinct from the claimed 3-amino-tetrahydrocarbazole compounds.

Does the patent cover all 5-HT1 agonists?

No. It covers a defined chemical genus of substituted tetrahydrocarbazoles and methods using those compounds. It does not cover every compound with 5-HT1 agonist activity.

Can an expired patent still be relevant in a patentability search?

Yes. Its disclosure can be prior art against later patent applications, even though its claims no longer provide enforceable exclusionary rights.

Does claim 17 cover every migraine tablet?

No. Claim 17 requires a compound within the claimed formula I or IA structure. A tablet containing a different active ingredient falls outside the claim.

Is a separate patent required to protect a commercial salt or hydrate?

Not necessarily. The claims expressly include physiologically acceptable salts, solvates and hydrates. A later patent could still provide separate protection for a particular solid form, formulation or manufacturing process.

References

1. U.S. Patent No. 5,827,871. (1998). 3-Amino-1,2,3,4-tetrahydrocarbazoles, processes for their preparation and pharmaceutical compositions containing them. United States Patent and Trademark Office.

2. United States Code, 35 U.S.C. § 154. Patent term.

3. United States Code, 35 U.S.C. § 271(e)(2). Infringement and abbreviated new drug applications.

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

5. U.S. Food and Drug Administration. (2024). Approved drug product and patent listing requirements. 21 C.F.R. §§ 314.53, 314.94.

Drugs Protected by US Patent 5,827,871

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 5,827,871

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9113802	Jun 26, 1991

International Family Members for US Patent 5,827,871

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0591280		SPC/GB03/014	United Kingdom
European Patent Office	0591280		C00591280/01	Switzerland
European Patent Office	0591280		C300103	Netherlands