GSK Paxil NDA Covers Hemihydrate And Anhydrous Paroxetine, Company Says

GlaxoSmithKline's Paxil NDA is not limited to the crystalline hemihydrate form of paroxetine marketed by the company, GSK maintained in a D.C. federal court filing.

In its reply to Apotex' motion for preliminary injunction against the late-listing of six Paxil patents, GSK contended that the Paxil NDA relied on clinical trials involving both the hemihydrate and the anhydrous versions of paroxetine hydrochloride (¹ (Also see "FTC Asks FDA To Clarify "Orange Book" Listing Criteria In Citizen Petition" - Pink Sheet, 28 May, 2001.)).

The SmithKline Beecham (now GSK) "NDA was not, in fact, limited to a single crystalline form of paroxetine hydrochloride," the company said. "To the contrary, SB developed the hemihydrate form during the course of clinical trials involving both the hemihydrate and the anhydrous forms."

Apotex argued in its May 8 motion that some of the late-listed patents are for the anhydrous form of paroxetine, which is not the FDA approved product, and therefore should not be allowed. However, the drug is listed in the 'Orange Book' simply as paroxetine hydrochloride, without making reference to hemihydrate or anhydrous.

GSK noted that while Apotex is seeking that paroxetine be limited to a single crystalline form for late-listed patents, the generics firm has filed Paragraph IV certifications to paroxetine hydrochloride, without reference to its hemihydrate form.

"There is simply no warrant in the [Waxman-Hatch] Act to define that the active ingredient...be limited to a single crystalline form for" listing patents in the Orange Book, "and then to expand the definition to all crystalline forms for the purposes of submitting an ANDA," the company said.

The Federal Trade Commission refers to the late-listed Paxil patents in a recent citizen petition asking FDA to clarify its position on Orange Book listings. "The anhydrous form is not an approved component of the drug product Paxil," the commission maintained.

GSK is asking the court to dismiss Apotex' motion for a preliminary injunction on the ground that the generics company cannot show the irreparable harm that is needed for such an injunction. Apotex does not face any immediate harm because the 30-month stay relating to GSK's '944 patent does not expire until May 2003, GSK contended.

Apotex has argued that patent No. 6,113,944, which covers paroxetine made using a direct compression method, does not claim Paxil made by wet granulation method as per the original NDA.

However, GSK noted that FDA approved a supplemental NDA allowing the company to manufacture Paxil via direct compression. "SB has manufactured Paxil in directly-compressed tablets for the last three years," the company said.

"SB's '944 patent therefore claims the FDA-approved drug product in the form actually marketed by SB," GSK said.

GSK also asserted that Apotex cannot claim injunctive relief against the 5,872,132 and 6,121,291 patents as GSK has not enforced these patents. Hence, there is no injury to Apotex caused by the two patents, GSK said.

GSK is asking the D.C. court "to defer to the Philadelphia court," which is trying the company's multiple Paxil-related patent infringement suits against Apotex, as well as another Apotex motion for injunction. The D.C. court would only duplicate work for itself if it chose to take on the case, GSK said.

GSK cited D.C. federal court Judge Ricardo Urbina's buspirone ruling in March, in favor of Mylan, which "emphasized that a 'critical factor' in his decision to maintain the [Mylan] case was that no parallel patent infringement suit was pending elsewhere." The D.C. court ordered Bristol to delist a buspirone patent and instructed FDA to grant approval of generic buspirone March 13 (² (Also see "Mylan Buspirone Launch Awaits Bristol Appeal Of BuSpar Patent Order" - Pink Sheet, 19 Mar, 2001.)).

FDA is appealing the D.C. court's order against the agency in the Mylan case. Mylan "had no basis for making FDA a defendant and the district court erred in enjoining FDA to immediately approve the ANDA," the agency maintained.

The "court should have limited its decision to ordering the innovator to request FDA to de-list the patent," the agency said. Oral arguments for the appeal before the D.C. circuit court are scheduled to begin in mid-July.