Donepezil (Aricept) 5 and 10 mg tablets: Apotex filed DJ request in a bid for generic approval

Reuters has reported Here that Generic player Apotex in a bid to trigger 180 days exclusivity of generic player Ranbaxy has filed Declaratory Judgment request of non-infringement against innovator Esai’s Orange Book listed patents on Donepezil Hydrochloride (Aricept) 5 and 10 mg tablets in the U.S. District Court for the Middle District of North Carolina

Following patents are listed In the Orange book for 5 and 10 mg tablets of Aricept:

US4895841 (Expiry: NOV 25,2010)- Product patent

US5985864 (Expiry: DEC 30,2016)- Polymorph (Form-II, III, IV and V)

US6140321 (Expiry: DEC 30,2016)-polymorph

US6245911 (Expiry: DEC 01,2018)-Polymorph A, B and C

US6372760 (Expiry: MAR 31,2019)- Formulation

Apotex has filed ANDA with para III certification against ‘841 product patent and Para IV against rest of the patents.

The first ANDA was filed for this product around early 2003 by generic player Ranbaxy, accordingly, it’s a pre-medicare, prescription drug improvement, and modernization act of (MMA) case, wherein, generic company were eligible as First Para IV filer by filing patent specific para IV filing. Probably, Ranbaxy filed para III against Product patent and para IV against rest of the patents and innovator choose not to initiate litigation against Ranbaxy.

Now, to trigger 180 days clock of First para IV filer, following is desirable:
1) A court decision of patent invalidity or non-infringement by subsequent generic players
2) By any one of the first to file generic enter into the market

In case of ANDA filed prior to MMA act, a bottleneck can occur when the first para IV filer does not enter the market and innovator refuses to sue subsequent generic player, thereby preventing the finding of invalidity or non-infringement.

Ranbaxy and Teva are first para IV filer for this product. Teva, who has litigated with the innovator on invalidation of product patent ‘841 has got adverse decision from court on preliminary injunction decision as reported by us Here .

As per complaint, Apotex argues that due to Ranbaxy’s cGMP problems, Ranbaxy would not be able to get final FDA approval and launch the product after patent expiry, accordingly, a DJ action is necessary to remove the hurdles for subsequent ANDA filers.

Also, as per complaint, Apotex has highlighted the fact that USFDA has erroneous identified generic giant Teva as the first para IV filer.

Furthermore, the generic player Apotex has filed Citizen petition with USFDA on July, 2009 against First Para IV filer status of Teva for this product.

Donepezil (2-[(1-benzyl-4-piperidyl)methyl]- 5,6-dimethoxy-2,3-dihydroinden-1-one), marketed under the trade name Aricept (Eisai), is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. The USFDA first approved Aricept tablets in 1996. The drug is Tokyo-based Eisai's biggest product, with $2.16 billion in worldwide sales in the year ended in March 2007.