Details for Patent: 5,916,923
Summary for Patent: 5,916,923
| Title: | Venlafaxine for the treatment of generalized anxiety disorder | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | This invention provides a method of treating obesity, generalized anxiety disorder, post-traumatic stress disorder, late luteal phase disphoric disorder (premenstrual syndrome), attention deficit disorder, with and without hyperactivity, Gilles de la Tourette syndrome, bulimia iervosa or Shy Drager Syndrome in a mammal by administering to the mammal an effective amount of a hydroxycycloalkanephenethyl amine of the following structural formula: ##STR1## in which A is a moiety of the formula ##STR2## where the dotted line represents optional unsaturation;R1 is hydrogen or alkyl;R2 is alkyl;R4 is hydrogen, alkyl, formyl, or alkanol;R5 and R6 are, independently, hydrogen, hydroxyl, aakyl, alkoxy, alkanoyloxy, cyano, nitro, alkylmercapto, amino, alkylamino, dialkylamino, alkanamido, halo, trifluoromethyl, or taken together, methylene dioxy;R7 is hydrogen or alkyl; andn is 0, 1, 2, 3, or 4;or a pharmaceutically acceptable salt thereof. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Richard L. Rudolph, G. Virginia Upton | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Wyeth LLC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US08/835,780 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Drug Patent 5,916,923: Claim Scope, Expiration, Orange Book Status, and Venlafaxine Patent LandscapeUS Patent 5,916,923 protected the use of venlafaxine, including pharmaceutically acceptable salts such as venlafaxine hydrochloride, to treat generalized anxiety disorder. The patent did not claim venlafaxine itself, an extended-release formulation, a manufacturing process, or every psychiatric use. Its enforceable scope was limited to method-of-treatment claims requiring administration of venlafaxine to a mammal with generalized anxiety disorder. The patent issued on June 29, 1999, and its 20-year patent term expired in December 2017 based on the underlying application timeline. The claims are therefore no longer enforceable in the United States. Current commercial risk from US Patent 5,916,923 is zero, although its claims remain relevant to historical Orange Book strategy, Paragraph IV litigation, generic labeling, and the development of venlafaxine-based products. What drug does US Patent 5,916,923 cover?US Patent 5,916,923 covers venlafaxine, chemically identified in the claims as: 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol The patent also covers pharmaceutically acceptable salts of that compound. The principal commercial salt is venlafaxine hydrochloride, the active ingredient in Effexor and Effexor XR.
The claim language is directed to therapeutic use. It does not create a new chemical-entity monopoly over venlafaxine. What are the claims of US Patent 5,916,923?What does independent claim 1 cover?Claim 1 covers a method of treating generalized anxiety disorder in a mammal by administering an effective amount of venlafaxine or a pharmaceutically acceptable salt. The principal limitations are:
The claim is broad as to dose, formulation, route, and dosing frequency, subject to the requirement that the amount be effective for treating generalized anxiety disorder. Claim 1 does not expressly require:
The claim’s practical scope would have covered labeled administration of venlafaxine for generalized anxiety disorder, regardless of whether the product was sold as an immediate-release or extended-release dosage form, unless another limitation narrowed the accused method. What does dependent claim 2 cover?Claim 2 incorporates claim 1 and limits the effective amount to a daily dose of approximately 50 mg/day to 375 mg/day. This range encompasses:
The use of “about” gives the claim some tolerance around the stated endpoints. The scope would depend on ordinary claim construction and the evidence concerning clinically equivalent dosing. What does dependent claim 3 cover?Claim 3 incorporates claim 1 and limits the daily dose to approximately 75 mg/day to 200 mg/day. Claim 3 is narrower than claim 2. Every dose within claim 3 also falls within claim 2, but claim 2 covers doses below 75 mg/day and above 200 mg/day that remain within the 50 mg/day to 375 mg/day range.
How strong was the patent scope of US 5,916,923?The patent had moderate historical relevance but limited product-level breadth. Strengths of the claimsThe claims had several commercially meaningful characteristics:
Limitations of the claimsThe patent did not prevent:
The patent also did not claim a specific pharmaceutical composition. A product containing venlafaxine hydrochloride could fall outside the patent if it was not used to treat generalized anxiety disorder. When did US Patent 5,916,923 expire?US Patent 5,916,923 issued June 29, 1999. Its term ran for 20 years from the applicable nonprovisional filing date and expired in December 2017. The patent is now expired.
The patent’s expiration eliminated the method-of-use barrier created by claims 1 through 3. It did not automatically determine the expiration of every other venlafaxine patent. Composition, extended-release, crystal-form, manufacturing, and formulation patents belonged to separate patent families with separate term calculations. What was the FDA and Orange Book status of the patent?Effexor was originally approved as an immediate-release venlafaxine product for depression. Effexor XR later expanded the commercial product line through an extended-release formulation and additional psychiatric indications, including generalized anxiety disorder. A use patent can be submitted for Orange Book listing when it claims an approved method of using the drug. FDA Orange Book listings historically played an important role in generic venlafaxine approval because an ANDA applicant had to address listed patents through one of four certifications:
After expiration, US Patent 5,916,923 could support a Paragraph II certification. During its active term, a generic applicant seeking approval for a product or label covering generalized anxiety disorder could have faced a Paragraph IV certification or a label carve-out strategy under the Hatch-Waxman Act. The Orange Book status of a specific patent number can change as FDA updates its patent database. The legally important point is that the patent’s term has ended, so any historical listing no longer creates a current barrier to approval or marketing. Which patents formed the broader venlafaxine patent estate?The venlafaxine estate was divided into several technical categories. US Patent 5,916,923 was the generalized anxiety disorder use patent, while other patents addressed the molecule, dosage forms, and controlled release.
US Patent 4,535,186 was the foundational venlafaxine patent. Its term expired long before US Patent 5,916,923. The later use patent therefore operated as an indication-specific layer over an already established active pharmaceutical ingredient. The most commercially important additional protection involved extended-release venlafaxine. Effexor XR generated a separate patent strategy because the controlled-release product had a different formulation and release profile from immediate-release venlafaxine. What formulation patents protected Effexor XR?The principal formulation risk centered on controlled-release venlafaxine products. Such patents generally protected:
These patents were distinct from US Patent 5,916,923. A formulation patent could be infringed by making or selling a particular extended-release product even when the product was marketed for an indication outside generalized anxiety disorder. Conversely, infringement of the generalized anxiety disorder patent depended on the use of venlafaxine for that indication, not merely on the physical composition of an extended-release capsule. The commercial consequences were significant because an ANDA applicant could attempt to avoid a method-of-use patent through a skinny label while still needing to address formulation patents through Paragraph II, III, or IV certifications. What Paragraph IV challenges affected venlafaxine?Venlafaxine became a major generic-entry product after the expiration of the principal composition and extended-release barriers. Generic applicants challenged or addressed Effexor and Effexor XR patents through the ANDA process. The relevant litigation issues generally included:
The historical Paragraph IV disputes were directed primarily at formulation and extended-release patents rather than at the now-expired generalized anxiety disorder claims. Once US Patent 5,916,923 expired, a Paragraph IV challenge to that patent ceased to provide a commercial advantage because the applicant could rely on a Paragraph II expiration certification. Did US Patent 5,916,923 create biosimilar risk?No. Venlafaxine is a synthetic small-molecule antidepressant. It is regulated through the abbreviated new drug application pathway for generics, not through the biosimilar pathway under section 351(k) of the Public Health Service Act. The applicable competitive risks were:
The FDA Purple Book and biosimilar interchangeability framework are not relevant to venlafaxine. Which companies challenged or competed against the venlafaxine franchise?The competitive landscape included both generic manufacturers and branded companies with competing treatments for generalized anxiety disorder. Generic manufacturersGeneric venlafaxine and venlafaxine extended-release products have been marketed by multiple manufacturers, including companies such as:
The precise set of approved suppliers varies by dosage strength, formulation, and market period. Generic competition focused on both immediate-release venlafaxine and extended-release products. Branded competitorsVenlafaxine competed with:
Duloxetine was the closest branded SNRI comparator. SSRIs competed directly in generalized anxiety disorder because they were widely used as first-line pharmacologic treatments. What licensing and ownership transactions affected the patent estate?The original commercial rights were associated with American Home Products, which later changed its corporate name to Wyeth. Pfizer acquired Wyeth in 2009. The transaction transferred the relevant branded pharmaceutical business and associated intellectual property into Pfizer’s portfolio. No separate public license is generally identified as the primary basis for US Patent 5,916,923. The material ownership sequence was:
The patent’s ownership history matters for historical litigation standing, Orange Book submissions, and settlement agreements. It does not extend the patent term. What generic launch scenarios existed under the patent?Before expiration, four scenarios were commercially relevant. Scenario 1: Launch after Paragraph III certificationA generic applicant could acknowledge the patent and wait until the listed expiration date. This reduced litigation risk but delayed entry. Scenario 2: Paragraph IV challengeThe applicant could allege that the patent was invalid, unenforceable, or not infringed. A Paragraph IV notice could trigger patent litigation and potentially create a 30-month stay of FDA approval under the Hatch-Waxman framework. Scenario 3: Skinny-label launchThe applicant could remove generalized anxiety disorder from its proposed label if the remaining approved uses were outside the patent claims. The feasibility of this route depended on the FDA label, prescribing information, promotional conduct, and whether the indication could be practically omitted without creating regulatory or infringement problems. Scenario 4: Post-expiration launchAfter December 2017, an applicant could market venlafaxine for generalized anxiety disorder without infringing US Patent 5,916,923, assuming no other live patent applied. What geographic coverage did the patent have?US Patent 5,916,923 covered only conduct within the territorial reach of US patent law. It did not directly protect venlafaxine use in Europe, Canada, Japan, China, or other jurisdictions. The international estate required separate national or regional filings. Relevant international protection could have included:
Expiration dates, claim scope, regulatory linkage, and litigation outcomes had to be assessed country by country. Expiration of the US patent did not establish freedom to operate globally, although most corresponding foreign rights for a 1990s use patent would also be expected to have expired by the 2020s. What manufacturing and intellectual-property barriers remained after expiration?Expiration of US Patent 5,916,923 removed only the generalized anxiety disorder method-of-use barrier. Other barriers could have included:
These barriers were more important for venlafaxine extended-release products than for conventional immediate-release tablets. A manufacturer could produce generic venlafaxine after patent expiration but still need to demonstrate bioequivalence, manufacturing consistency, and compliance with FDA current good manufacturing practice requirements. What was the revenue exposure of the patent?US Patent 5,916,923 protected one indication within the broader Effexor franchise. It did not protect all venlafaxine revenue. Effexor became one of Wyeth’s largest products, with annual sales reported at several billion dollars before generic erosion. Pfizer reported Effexor revenue of approximately $3.8 billion in 2008, before the full impact of generic competition and the later loss of exclusivity.[4] The patent’s revenue contribution was therefore indirect. Its value came from:
Because depression and other indications generated substantial venlafaxine use, the patent alone would not have protected the entire product franchise. Formulation patents and regulatory exclusivity had greater influence over total product revenue. Key Takeaways
FAQs About US Patent 5,916,923Is US Patent 5,916,923 still enforceable?No. The patent expired in December 2017 after the applicable 20-year patent term. Does the patent cover venlafaxine hydrochloride?Yes. Claim 1 expressly covers venlafaxine and pharmaceutically acceptable salts. Venlafaxine hydrochloride is the principal commercial salt. Does the patent block generic venlafaxine for depression?No. The quoted claims are limited to treating generalized anxiety disorder. Other venlafaxine uses were subject to separate patents, labeling rules, and regulatory requirements. Can a company market extended-release venlafaxine after this patent expired?Yes, subject to FDA approval and any other applicable patent or regulatory rights. US Patent 5,916,923 does not claim the extended-release formulation itself. Was a biosimilar application required for generic venlafaxine?No. Venlafaxine is a small-molecule drug. Generic manufacturers use the ANDA pathway rather than the biosimilar pathway. References
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Drugs Protected by US Patent 5,916,923
| 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 |
International Family Members for US Patent 5,916,923
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 213407 | ⤷ Start Trial | |||
| Austria | 342715 | ⤷ Start Trial | |||
| Austria | 392893 | ⤷ Start Trial | |||
| Australia | 5831298 | ⤷ Start Trial | |||
| Australia | 6592994 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
