Escitalopram [Lexapro (R)]

Analysis of the Lexapro case.

UPDATE: May, 2007:

US:

The appeal in this case was heard on 9 May 2007 before the U.S. Court of Appeals for the Federal Circuit, and both the parties involved are awaiting a decision.

United Kingdom:

On 4^th May 2007, a UK court ruled that escitalopram is innovative and new, that it was not obvious to separate the molecule and that it would lead to the benefits offered by escitalopram. However, the court found in favour of the generic plaintiffs [Generics UK, TEVA and Arrow] with reference to specific English case law. Lundbeck has appealed the ruling.

Citation: [2007] EWHC 1040 (Pat)

UPDATE: 11 NOV, 2006:

TEVA has filed an appeal against the unfavourable decision from the Dist. Court of Delaware.

UPDATE: 14 July, 2006:

Forest Laboratories, Inc. said today that the U.S. District Court for the District of Delaware has determined that the U.S. patent covering Escitalopram, the active ingredient in Lexapro(R), is both valid, enforceable and infringed by Ivax/Teva's proposed generic product, thereby confirming Forest's and Lundbeck's patent rights for Lexapro(R), which expire in March 2012.

Analysis of the Lexapro case [Earlier Post].

A look at the main issues & post trial briefs filed by both parties.

Lexapro [generic name: Escitalopram] is a ‘+’ enantiomer of earlier drug - Citalopram.

It is marketed in US by Forest and forms a substantial chunk of its US revenues. The drug is an invention from the house of Lundbeck, which also was behind Citalopram. It is prescribed for adults suffering from depression and generalized anxiety disorder.

It has two patents listed on the US FDA Orange Book:

RE34712 having a ped exclusivity, with final expiry of 14/MAR/2012.

US6916941 having a ped exclusivity, with final expiry of 25/JAN/2023

RE34712 [originally US4943590] covers two novel enantiomers of Citalopram. The claimed novelty is that 5-HT uptake inhibition resides in the (+)-citalopram enantiomers. It protects this (+)-1-(3- Dimethylaminopropyl) -1-(4'- fluorophenyl)-1,3- dihydroisobenzofuran-5- carbonitrile and non-toxic acid addition salts. Further, claims for its method of manufacture and formulation are also present.

US6916941 covers crystalline particles of escitalopram oxalate having a median particle size of at least 40 μm, further in the range of 50-200 μms. It also has method of manufacture and formulation claims covering the same.

Importantly, there is another pending patent: US2005147674 which is CIP from the ‘941 patent and is being prosecuted at USPTO. This application covers a tablet prepared from the crystalline particles of Escitalopram oxalate protected in the ‘941 particle size patent.

US scenario:

Teva was in litigation concerning this product in the U.S. District Court for the District of Delaware[Forest Labs. v. IVAX Pharms., No. 03-891]. A suit was brought against Teva's subsidiary IVAX in September 2003 involving its paragraph IV certification to U.S. Patent No. RE34,712. A trial was held in March 2006.

The case continued against IVAX [now owned by Teva] and Cipla. The trial was held in March 2006 and the post-trial briefing period ended on May 19th.

Importantly, IVAX [TEVA] was granted the final approval by the FDA for the generic version of this product on 22/MAY/06. Another notable point here is that Teva and Forest agreed in January 2006 that if Teva did launch prior to a decision in the patent suit, Teva would give Forest 45 days notice.

In its post-trial brief, IVAX argued that the '712 patent is invalid for anticipation and obviousness, invalid for broadening reissue, and unenforceable for inequitable conduct. In its lead argument, IVAX argues that a prior art reference, Smith, describes (+) and (-) citalopram as individual enantiomers in a form separated from each other. Forest countered in its post-trial brief that Smith does not anticipate the '712 patent because it does not enable one of skill in the art to make substantially pure (+)-citalopram without undue experimentation.

In a July 2006 ruling, the Dist. Ct held that U.S. patent covering Escitalopram, the active ingredient in Lexapro^(R), is both valid, enforceable and infringed by Ivax/Teva's proposed generic product. © Sandeep K. Rathod, 2007

In 2005, a settlement was reached with Alphapharm. Under the settlement, Lundbeck and Forest will give Alphapharm exclusive rights to distribute generic versions of Lexapro when Forest's patent on the drug expires. Alphapharm, in turn, will pay Forest a portion of the generic sales's profit, and agreed that the Forest patent is valid. Forest and Lundbeck also will reimburse some of the costs Alphapharm incurred in defending itself in the patent litigation.