Details for Patent: 7,081,249
Summary for Patent: 7,081,249
| Title: | Compositions and methods for minimizing adverse drug experiences associated with oxybutynin therapy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | The present invention provides compositions and methods for administering oxybutynin while minimizing the incidence and or severity of adverse drug experiences associated with oxybutynin therapy. In one aspect, these compositions and methods provide a lower plasma concentration of oxybutynin metabolites, such as N-desethyloxybutynin, which is presumed to be contributing at least in part to some of the adverse drug experiences, while maintaining sufficient oxybutynin plasma concentration to benefit a subject with oxybutynin therapy. The invention also provides isomers of oxybutynin and its metabolites that meet these characteristics of minimized incidence and/or severity of adverse drug experiences, and maintenance of beneficial and effective therapy for overactive bladder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Steven W. Sanders, Charles D. Ebert | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Allergan Sales LLC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US10/731,039 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Patent Claim Types: see list of patent claims | Use; Composition; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 7,081,249: Oxybutynin Transdermal Patch Claims, Expiration, Litigation and Patent LandscapeUS Patent No. 7,081,249 covers transdermal oxybutynin therapy designed to reduce exposure to N-desethyloxybutynin, the metabolite associated with anticholinergic adverse effects such as dry mouth. Its core invention is a pharmacokinetic treatment method, not merely an oxybutynin patch. The claims require a transdermal delivery system that produces specified oxybutynin-to-metabolite exposure ratios and metabolite concentration limits. The patent issued July 25, 2006, from an application directed to transdermal oxybutynin delivery. Its statutory term has expired. The patent therefore does not currently block generic or alternative transdermal oxybutynin products in the United States. What does US Patent 7,081,249 protect?The patent protects three related claim categories:
The independent claims are claims 1, 20 and 39.
The patent’s practical focus is the pharmacokinetic difference between oral and transdermal oxybutynin. Oral oxybutynin undergoes substantial first-pass metabolism to N-desethyloxybutynin. The transdermal route reduces first-pass metabolism and is intended to maintain therapeutic oxybutynin exposure with lower metabolite exposure. The FDA label for Oxytrol describes the product as a 3.9 mg/day oxybutynin transdermal system applied twice weekly. [1] What pharmacokinetic limits are required by the patent?The principal quantitative limitation is the relationship between oxybutynin and N-desethyloxybutynin exposure.
These are outcome-based limitations. A product does not fall within the claims merely because it contains oxybutynin or uses a transdermal patch. The accused product must produce, or be shown to produce, the claimed pharmacokinetic profile. The AUC ratio is particularly significant. The claims use the ratio of total oxybutynin exposure to total N-desethyloxybutynin exposure. A system producing a high oxybutynin exposure but also a high metabolite exposure could fall outside the claimed range. Conversely, a system with relatively low metabolite formation could satisfy the ratio even if its absolute oxybutynin exposure differs from the commercial Oxytrol profile. How do the dependent claims narrow the scope?Claims 2 through 19 narrow the method of claim 1. They address:
Claims 11 through 14 require administration for approximately 24 to 96 hours, with narrower claims directed to 72, 84 and 72-to-96-hour periods. Claims 15 through 19 address patch sizes from 13 to 39 cm² and the use of multiple 13 cm² patches. The stereochemical limitations are narrower than the broad oxybutynin claims. Claim 6 expressly covers R-oxybutynin, while claim 5 covers a mixture of R- and S-oxybutynin. The metabolite limitations cover either enantiomer of N-desethyloxybutynin or a combination. What is the scope of claim 39?Claim 39 is the most technically specific independent claim. It combines four limitation groups:
The enhancer group includes:
The phrase “consisting essentially of” may limit the enhancer component to the listed classes and components that do not materially alter the invention’s basic characteristics. The claim is therefore narrower than claim 1 with respect to formulation composition, but potentially more useful against a commercial patch with a known enhancer system and a matching physical design. What formulations and delivery systems are protected?The patent does not claim every oxybutynin transdermal formulation. It claims formulations by reference to their pharmacokinetic result and, in claim 39, by specified enhancer classes. The claims encompass:
The claims do not expressly require the commercial Oxytrol brand, a particular adhesive, a particular backing layer, a specific drug loading, or a particular manufacturing process. Those limitations may appear in the specification, regulatory filings or related patent families, but they are not required by the quoted independent claims. What is the relationship between the patent and Oxytrol?Oxytrol is an oxybutynin chloride transdermal system approved for overactive bladder. The prescription product was approved by FDA in 2003. FDA later approved Oxytrol for over-the-counter use in women aged 18 and older in 2013. [1,2] The commercial system uses a transdermal patch delivering approximately 3.9 mg of oxybutynin per day. The labeling instructs application of one patch twice weekly, corresponding generally to replacement every three to four days. [1] Those commercial characteristics align closely with the claim architecture:
The patent was directed at the pharmacokinetic advantages of the transdermal product rather than simply the chemical identity of oxybutynin. When did US Patent 7,081,249 lose exclusivity?US Patent 7,081,249 is expired. Its 20-year patent term ran from the relevant nonprovisional filing date, subject to any applicable patent-term adjustment. The patent is no longer an enforceable exclusionary right against a generic, branded, compounded or otherwise competing oxybutynin transdermal product. The patent’s expiration is separate from FDA exclusivity. FDA approval does not extend the patent term. Any regulatory exclusivity associated with the original Oxytrol approval also has expired. The Orange Book’s current treatment of the product and any associated patents must be distinguished from the historical listings that existed during the patent’s enforceable term. [3] What was the Orange Book status of oxybutynin transdermal products?Oxytrol was listed in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, under oxybutynin chloride transdermal system. Orange Book listings historically identified product patents and regulatory exclusivity relevant to abbreviated new drug applications. [3] The relevant legal significance was limited to the period before patent expiration. After expiration, an Orange Book-listed patent no longer provides an active patent barrier, even if historical records continue to identify the patent. The principal regulatory pathways were:
An OTC switch does not by itself create a new patent term for the existing transdermal delivery technology. Which companies challenged or competed with the patent?Publicly identifiable commercial competition has centered on oxybutynin transdermal systems rather than on a single high-profile biologic-style patent dispute. Generic-drug manufacturers have had incentives to target the underlying oxybutynin transdermal product after patent expiration, while branded competitors have included oral extended-release oxybutynin and other overactive-bladder therapies. The competitive set includes:
The principal market risk to Oxytrol was not limited to literal copying of a 39 cm² patch. A competitor could design around the patent by using a different patch size, delivery duration, enhancer, stereochemical composition or pharmacokinetic profile, subject to other patent rights. What Paragraph IV risks applied to this patent?Before expiration, an ANDA applicant could have challenged the patent through a Paragraph IV certification. The central arguments would likely have included:
The pharmacokinetic limitations create both an enforcement advantage and a litigation burden. They distinguish the claims from a simple patch-composition patent, but they require reliable clinical or comparative PK evidence. An ANDA sponsor could argue that the patent claims a desired result without adequately claiming the physical features that necessarily produce it. No current Paragraph IV challenge can restore an exclusionary right after expiration. Historical litigation activity would affect damages, launch timing or settlement interpretation, but not present-day freedom to market. How strong was the patent estate?The patent had meaningful historical value because it aligned with the commercial design of Oxytrol and claimed the reduced-metabolite rationale behind transdermal administration. Its strongest features were:
Its weaknesses included:
The expired status now dominates the commercial analysis. Historical claim strength matters for past infringement and settlement interpretation, but it does not create current market exclusivity. What litigation and settlement issues are relevant?A party evaluating historical Oxytrol litigation should separate four issues:
Patent settlements can contain launch dates, supply arrangements, licenses, authorized-generic provisions or no-challenge clauses. The existence of a patent does not establish that a settlement occurred, and a settlement does not establish that the patent was valid or infringed. The patent’s expiration eliminates prospective injunction risk under this patent. It does not eliminate potential historical damages claims for conduct occurring before expiration, subject to statutory limitations and litigation outcomes. What generic launch scenarios exist after expiration?Three principal scenarios are available: Direct generic transdermal launchA sponsor may seek an ANDA for oxybutynin chloride transdermal system if it can satisfy FDA requirements for pharmaceutical equivalence, bioequivalence and device or delivery-system comparability. The sponsor would still need to address any unexpired patents in the relevant product listing, but US 7,081,249 is no longer a barrier. Design-around transdermal systemA competitor may use a patch outside the 13-to-39 cm² range, a different replacement interval, an alternative enhancer or a different oxybutynin stereochemical composition. Design-around strategies reduce dependence on the expired patent and may avoid historical infringement exposure. Reformulated or alternate-route productA sponsor may develop oral extended-release oxybutynin, a different antimuscarinic, a beta-3 agonist, or a combination product. These products compete clinically but are not generally exposed to the transdermal PK limitations of US 7,081,249. What geographic coverage did the patent provide?US 7,081,249 provided rights only in the United States. Corresponding foreign applications, if any, required separate examination and separate expiration analysis. A US expiration does not automatically establish the status of foreign family members. For a multinational launch, the relevant analysis must be conducted separately for:
The US claims also do not establish freedom to operate for manufacturing in another country if the product is imported into the United States. Importation, sale and use can each create separate US infringement issues under the Patent Act. Key Takeaways
FAQs About US Patent 7,081,249Is US 7,081,249 still enforceable?No. The patent has expired and no longer provides an enforceable US patent exclusion. Does the patent cover all oxybutynin patches?No. It covers patches and treatment methods meeting the claimed PK conditions. Claim 39 adds specific size, duration and enhancer limitations. Does a 39 cm² oxybutynin patch automatically infringe?No. Patch size alone is insufficient. The product would also need to satisfy the claimed treatment, PK, duration and, for claim 39, enhancer limitations. Does the patent cover oral oxybutynin?No. The claims require transdermal administration or a transdermal patch. Does R-oxybutynin fall within the claims?Yes, claim 6 expressly recites R-oxybutynin, and claim 25 provides a corresponding article-of-manufacture limitation. Can a generic launch after the patent expires still face FDA barriers?Yes. FDA requirements, other patents, device comparability, manufacturing controls and regulatory exclusivity must be evaluated separately. US 7,081,249 itself is no longer a patent barrier. References
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Drugs Protected by US Patent 7,081,249
| 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 7,081,249
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 488233 | ⤷ Start Trial | |||
| Australia | 2001253782 | ⤷ Start Trial | |||
| Australia | 2003287377 | ⤷ Start Trial | |||
| Australia | 2003294239 | ⤷ Start Trial | |||
| Australia | 2010200418 | ⤷ Start Trial | |||
| Australia | 2012216593 | ⤷ Start Trial | |||
| Australia | 5378201 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
