A patent term extension for Pfizer's Norvasc applies only to the besylate salt of amlodipine, Dr. Reddy's said in its motion to dismiss Pfizer's patent infringement suit.

Arguing that patent term extension extends only the portion of the patent that covers the approved product, Dr. Reddy's says that Pfizer's basic product patent for amlodipine (No. 4,572,909) should not be granted an extension.

With Waxman/Hatch, "Congress intended to compensate NDA holders for regulatory delays associated with its approved product by extending patent coverage for that approved product," Dr. Reddy's motion states.

The restoration period of the patent applies only to the product on which the patent extension was based, Dr. Reddy's said. The brief cited the 1996 decision in Merck v. Kessler, which found that "the restoration period of the patent does not extend to all products protected by the patent but only to the product on which the extension was based."

The Patent & Trademark Office's "determination of eligibility for a PTE is made 'solely on the basis of the representations contained in the application for the extension,'" Dr. Reddy's said.

Thus, because "Pfizer stated in its PTE application that both the approved product and the active ingredient are 'amlodipine besylate,'" the extension only applies to the besylate salt of amlodipine, Dr. Reddy's maintained.

The '909 patent is listed in the "Orange Book" as expiring in January 2007 with pediatric exclusivity. Dr. Reddy's acknowledges the validity of the patent but not the extension, and is seeking approval to launch on Aug. 26, 2003.

Dr. Reddy's submitted a 505(b)(2) application for the maleate salt of amlodipine in December 2001. Although Pfizer conducted clinical trials with the maleate salt, the company received regulatory approval to market the besylate salt of amlodipine (¹ Also see "Pfizer Norvasc Challenges: Mylan ANDA, Dr. Reddy’s 505(b)(2)" - Pink Sheet, 21 October, 2002., p. 20).

Dr. Reddy's motion to dismiss is scheduled to be argued in mid-December in New Jersey Federal Court.

Pfizer acknowledged that while a limitation for patent term extensions does exist, it applies to pharmaceutical uses rather than to the product itself.

"The limitation is to 'any use approved for the product' under specified drug-related statutes including the new drug review section of the Federal Food, Drug and Cosmetic Act," Pfizer's brief says. The company noted that Dr. Reddy's is seeking approval for the use of its amlodipine in hypertension and angina, the same indications for which Norvasc is approved.

The document also maintains that even if the patent term extension were limited to the defined approved product, the maleate salt of amlodipine should be included in that definition for Norvasc. "Pfizer was unable, during the nearly decade-long period of studies and FDA review, to exploit its patent rights on amlodipine or its maleate or besylate salt forms," the brief says.

Furthermore, Pfizer maintained that the statutory term "approved product" defines product as "'active ingredient...including any salt or ester of the active ingredient....Consequently, 'approved product' does not have its everyday meaning, but rather encompasses multiple ingredients."

The company noted that "Reddy is relying upon Pfizer's maleate and other studies, while, at the same time, seeking to circumvent Pfizer's patent that was restored to compensate it for the years in which patent rights were unusable during FDA review of those very studies."

The arguments regarding use of Pfizer's Norvasc studies parallel the company's citizen petition against Dr. Reddy's amlodipine 505(b)(2). Pfizer maintains that Dr. Reddy's should submit original data establishing the safety of its proposed amlodipine product.

"The proprietary data in the NDA for Norvasc cannot establish the safety of Reddy's proposed product. These data were generated from studies of a uniquely-manufactured amlodipine maleate product (in capsule form) that Pfizer never commercialized," the petition says.

During Norvasc development, Pfizer encountered stability and tableting problems with the maleate salt, which caused the company to switch to the besylate salt. Subsequently, Pfizer was able to control maleate stability problems with "unique" manufacturing techniques, which allowed the company to use maleate salt clinical data in its Norvasc application.

Pfizer asked Dr. Reddy's to "independently establish the purity and stability of its amlodipine maleate product, quantify and qualify any impurities (including in vitro toxicity and long-term oral carcinogenicity studies in rodents), and establish appropriate manufacturing specifications for its product."

The petition, submitted Oct. 11, requests that FDA "immediately revoke its acceptance for filing...and/or deny approval" of Dr. Reddy's amlodipine 505(b)(2) if its application "relies on any non-public, proprietary data in Pfizer's" NDA for Norvasc.

Pfizer argued that FDA's use of innovator proprietary data in its review of a section 505(b)(2) application, such as Dr. Reddy's, is prohibited under the FD&C Act, the Administrative Procedure Act, and the Takings Clause of the Fifth Amendment.

Pfizer and Pharmacia made similar arguments in a July 27, 2001 citizen petition asking FDA to revise draft guidance and permit only published data to be used in support of 505(b)(2) applications (² Also see "Pfizer, Pharmacia Protest Inclusion Of Drug Innovator Data In "Paper NDAs"" - Pink Sheet, 20 August, 2001., p. 16).

Pfizer also asked that, should FDA approve Dr. Reddy's amlodipine maleate using Pfizer's NDA for Norvasc, the agency "identify...any elements of the NDA for Norvasc upon which FDA relied so that Pfizer can determine whether FDA improperly relied upon non-public proprietary data."

Additionally, Pfizer asked that "A" therapeutic equivalence rating not be granted to Dr. Reddy's proposed product. Dr. Reddy's is not anticipating an "AB" rating for the product.

The company's petition noted that Norvasc is Pfizer's second best-selling drug. Norvasc's 2002 year-to-date U.S. sales are $1.3 bil., up 5% from 2001.

Dr. Reddy's received an "approvable" letter from FDA Oct. 21 for its amlodipine maleate. Final approval of the 505(b)(2) application is contingent upon the "the successful completion of ongoing discussions with the FDA regarding issues related to specific chemistry manufacturing controls and product labeling" as well as the patent case.

Pfizer Norvasc Patent Term Extension Coverage: The Product Or The Use?

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