Details for Patent: 5,464,864
Summary for Patent: 5,464,864
| Title: | Use of tetrahydrocarbazone derivatives as 5HT1 receptor agonists | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | PCT No. PCT/GB92/01082 Sec. 371 Date Dec. 23, 1993 Sec. 102(e) Date Dec. 23, 1993 PCT Filed Jun. 17, 1992 PCT Pub. No. WO93/00086 PCT Pub. Date Jan. 7, 1993. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Francis D. King, Laramie M. Gaster, Alberto J. Kaumann, Rodney C. Young | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Endo Pharmaceuticals Inc | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US08/167,846 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 5,464,864: Frovatriptan Patent Scope, Expiration, Orange Book Status, and Generic RiskUS Patent 5,464,864 covers frovatriptan, the 5-HT1B/1D receptor agonist marketed as Frova, together with its pharmaceutically acceptable salts, solvates, hydrates, therapeutic use in headache disorders, and pharmaceutical compositions. The patent issued on November 7, 1995, and its original US patent term expired on November 7, 2012, subject to any applicable patent-term adjustment or pediatric exclusivity. The claims do not cover every triptan. They focus on the defined tetrahydrocarbazole compound and products containing it. Because the patent has expired, it no longer creates a current US patent barrier to an otherwise approvable generic frovatriptan product. Any current market protection must arise from other patents, regulatory exclusivity, product-specific litigation, or commercial factors rather than enforceability of US Patent 5,464,864. What drug does US Patent 5,464,864 protect?The claimed compound is frovatriptan, chemically identified as the 3-methylamino-6-carboxamido tetrahydrocarbazole compound. Frovatriptan is generally administered as frovatriptan succinate and is used for the acute treatment of migraine attacks, with or without aura. The chemical claim, as reproduced in the question, covers:
The stereochemical point is material. Frovatriptan is a chiral compound. The legally relevant scope depends on the structural formula and definition in the issued patent, not only on the abbreviated text of claim 1. If the formula depicts the active 3R configuration, the claim may be limited to that stereoisomer and its permitted salt, solvate, or hydrate forms. What is the commercial identity of the compound?
The FDA-approved label identifies frovatriptan succinate as a selective agonist at serotonin 5-HT1B and 5-HT1D receptors. The label’s approved indication is narrower than the patent’s broad method language because FDA approval is based on the submitted clinical and regulatory record. [2] What does claim 1 of US 5,464,864 cover?Claim 1 is a product claim. It covers the defined frovatriptan molecule and its salt, solvate, and hydrate forms. Product claims generally provide the strongest form of pharmaceutical patent protection because infringement does not depend on the accused party’s intended indication. A manufacturer that makes, imports, sells, or offers for sale the claimed active ingredient can potentially infringe regardless of whether the product label identifies migraine, cluster headache, or another condition. Scope of the chemical claimThe claim reaches:
The claim does not expressly cover:
A salt claim can be commercially significant because the reference product is supplied as frovatriptan succinate. A generic manufacturer normally seeks approval for the same active moiety and a pharmaceutically acceptable salt or equivalent form. The expired status of the patent removes the principal product-claim obstacle in the United States. What do the method-of-treatment claims cover?Claims 2 through 5 cover administering the claimed compound to a patient for a condition in which a 5-HT1-like agonist is indicated. The claims create a hierarchy:
The supplied text states that claims 3 through 5 depend on claim 1. That appears structurally inconsistent with their subject matter because each is a treatment method and would ordinarily depend on claim 2. The issued patent must control for dependency and enforceability analysis. What conditions are covered?The method claims identify:
Claim 2 is potentially broader than the FDA-approved migraine indication. A patent can claim a use that is broader than the indication ultimately approved by FDA. The breadth is constrained by the claim’s requirement that the condition be one in which a 5-HT1-like agonist is indicated and that the administered product be the claimed compound. The method claims do not state a particular dose, route, tablet strength, treatment duration, or patient subgroup. Those omissions generally make the claims broader, although infringement still requires proof that the claimed steps occurred. What does claim 6 protect?Claim 6 covers a pharmaceutical composition containing:
This is a composition claim rather than a pure product claim or treatment claim. What formulations are protected?Claim 6 potentially covers conventional pharmaceutical preparations containing frovatriptan or an acceptable salt, including oral dosage forms with ordinary excipients. The claim is not limited to:
The carrier limitation requires a pharmaceutical composition, not merely bulk active ingredient. A tablet, capsule, solution, suspension, or other dosage form may fall within the claim if it contains the claimed compound and a physiologically acceptable carrier. The claim does not necessarily protect later-developed formulations that use a different active ingredient, a nonphysiologically acceptable carrier, or a chemically distinct derivative outside the claim. When did US Patent 5,464,864 expire?US Patent 5,464,864 issued on November 7, 1995. For a US patent subject to the pre-1995 patent-term regime, the ordinary term was generally 17 years from issue. On that basis, the patent expired on November 7, 2012. The patent’s term should be distinguished from FDA regulatory exclusivity.
The FDA may grant six months of pediatric exclusivity attached to qualifying listed patents. Pediatric exclusivity does not extend the patent’s legal term. It can delay certain FDA approvals or effective dates during the exclusivity period. [3] The existence and duration of any pediatric exclusivity must be determined from FDA’s product-specific exclusivity records rather than from the patent itself. What is the Orange Book status of frovatriptan?The Orange Book identifies patents and regulatory exclusivity associated with approved drug products. A patent listed for Frova or frovatriptan succinate does not remain enforceable after expiration, although its historical listing may remain relevant to the approval record and to earlier ANDA certifications. For an ANDA referencing frovatriptan, the principal Hatch-Waxman patent-certification categories would have included:
After expiration of US 5,464,864, a Paragraph II certification would ordinarily be the relevant certification for that patent. A Paragraph IV challenge would have been commercially relevant before expiration, particularly if the applicant sought a 180-day generic exclusivity position or wanted to clear the patent before its stated expiry. [4] The Orange Book analysis must be conducted by product, dosage form, and patent listing. The patent number alone does not establish whether other patents were listed for Frova, whether any listing was delisted, or whether a later formulation patent applied. Were Paragraph IV challenges likely to affect frovatriptan?A Paragraph IV certification against US 5,464,864 would have challenged either validity, enforceability, or infringement before the patent expired. The most likely technical strategies would have included:
The product claim would have posed the greatest challenge to a generic because a conventional frovatriptan product would ordinarily contain the claimed active ingredient. A method-of-use carve-out could address a method claim, but it would not avoid an unexpired composition or compound claim. No current Paragraph IV risk can arise from an expired patent. Any historical litigation must be separated from present enforceability. What patent litigation affects US Patent 5,464,864?The patent number, claim text, and issue data do not establish the complete litigation history. Patent litigation involving frovatriptan could include:
A settlement does not revive an expired patent. Its commercial effect would have been limited to the pre-expiration period, regulatory approval timing, launch restrictions, or other contractual terms. Any settlement analysis must distinguish:
The expiration of US 5,464,864 removes the possibility of an injunction based solely on that patent for future US sales. It does not eliminate potential historical damages claims for infringement occurring before expiration. How strong was the patent estate?US 5,464,864 had a strong claim position during its enforceable term because it combined three layers of protection:
The estate’s principal weakness was temporal. The patent issued in 1995 and expired in 2012, while Frova received FDA approval in 2001. The resulting post-approval patent life was approximately 11 years before ordinary expiration. Any patent-term extension or pediatric exclusivity would have affected the commercial timeline, but neither changes the underlying breadth of the claims. The method claims also present narrower enforcement opportunities than the chemical claim. They require proof of the claimed treatment method and can be affected by product labeling, physician behavior, pharmacy substitution, and induced-infringement theories. The compound and composition claims avoid much of that evidentiary burden. How does frovatriptan compare with other triptan patent estates?Frovatriptan’s patent profile differs from products such as sumatriptan, rizatriptan, naratriptan, zolmitriptan, and eletriptan because the core claim is directed to a tetrahydrocarbazole rather than an indole-based triptan structure.
Frovatriptan’s differentiated chemical structure reduced the relevance of patents directed to other triptans. Conversely, patents directed specifically to its stereochemistry, salt selection, crystallinity, formulation, or manufacturing process could have created separate barriers even after expiration of the core compound patent. What generic entry risks remain?The expired patent does not block a generic frovatriptan product. Remaining risks would be product-specific and could include:
A generic applicant would normally evaluate whether its proposed product contains the same active moiety, whether it uses a listed salt, whether the label includes or omits protected uses, and whether any additional patents remain listed for the reference product. There is no biosimilar pathway for frovatriptan. Frovatriptan is a small-molecule drug regulated through the ANDA pathway, not a biologic regulated under the Public Health Service Act. The relevant competitive products are generics, not biosimilars. [5] What is the geographic coverage of the patent?US Patent 5,464,864 provided rights only in the United States. It did not directly block manufacture, sale, or use in Europe, Japan, Canada, or other jurisdictions. International protection would depend on corresponding national patents and their individual:
A US expiration date cannot be applied to the global frovatriptan patent estate. The same compound may have had different expiration dates or claim outcomes in other jurisdictions. What manufacturing and intellectual-property barriers could remain?The core patent does not claim a particular synthetic route in the supplied claims. It therefore does not independently block every process used to manufacture frovatriptan after expiration. Separate process patents could have covered:
Process claims require process-specific comparison. A generic manufacturer can avoid a process patent by using a noninfringing route, but an API supplier may still face separate patent risks in the manufacturing jurisdiction or destination market. Key Takeaways
FAQsDoes US Patent 5,464,864 cover frovatriptan succinate?It covers the claimed frovatriptan compound and pharmaceutically acceptable salts. Frovatriptan succinate is the marketed salt form and would generally have been within the commercial scope of the patent during its enforceable term, subject to the exact issued claim construction. Can a generic manufacturer launch frovatriptan after expiration of US 5,464,864?Yes, expiration of the patent removes that patent as a US patent barrier. FDA approval, any other unexpired listed patents, regulatory exclusivity, and applicable litigation outcomes still govern the timing of a specific product launch. Does claim 2 cover all uses of frovatriptan?No. Claim 2 is limited by the requirement that the treatment address a condition for which a 5-HT1-like agonist is indicated. Claims 3 through 5 identify migraine, cluster headache, and vascular-disorder-associated headache as narrower claimed conditions. Is a frovatriptan formulation patent different from the compound patent?Yes. A formulation patent may cover a particular dosage form, excipient system, release profile, polymorph, or manufacturing method. Its term and infringement analysis are separate from US 5,464,864. Can the expired patent support a new patent on frovatriptan?The expired patent cannot be used to obtain a new patent on the same disclosed compound merely by repackaging the original disclosure. A later patent could potentially address a genuinely new and nonobvious formulation, polymorph, manufacturing process, dosing regimen, or patient population, subject to ordinary patentability requirements. References
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Drugs Protected by US Patent 5,464,864
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| >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: 5,464,864
| Foriegn Application Priority Data | ||
| Foreign Country | Foreign Patent Number | Foreign Patent Date |
| United Kingdom | 9113802 | Jun 26, 1991 |
| PCT Information | |||
| PCT Filed | June 17, 1992 | PCT Application Number: | PCT/GB92/01082 |
| PCT Publication Date: | January 07, 1993 | PCT Publication Number: | WO93/00086 |
International Family Members for US Patent 5,464,864
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| European Patent Office | 0591280 | ⤷ Start Trial | SPC/GB03/014 | United Kingdom | ⤷ Start Trial |
| European Patent Office | 0591280 | ⤷ Start Trial | C00591280/01 | Switzerland | ⤷ Start Trial |
| European Patent Office | 0591280 | ⤷ Start Trial | C300103 | Netherlands | ⤷ Start Trial |
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
