Pfizer Norvasc Patent: Will Court Limit Extension To “Approved” Product?

Dr. Reddy's reliance on Norvasc data in its 505(b)(2) application for amlodipine maleate could impact an appeals court's determination of whether Pfizer's patent term extension applies only to the approved besylate salt form of the drug.

During oral arguments July 9, an appellate panel questioned how Dr. Reddy's amlodipine maleate could fall outside the scope of a patent term extension for Norvasc (amlodipine besylate) when Reddy's "paper NDA" relies upon Pfizer's own data.

Pfizer is appealing a Newark federal judge's ruling that its patent term was extended only for the besylate form of amlodipine, and not for the amlodipine moiety (¹ (Also see "Pfizer Loses Norvasc Ruling: Rx Patent Extensions Are For Product, Not Use" - Pink Sheet, 23 Dec, 2002.), p. 15).

Pfizer's basic product patent (no. 4,572,909) covers amlodipine and its salts. When initially issued in 1986, the '909 patent was slated to expire on Feb. 25, 2003.

The Patent & Trademark Office granted Pfizer patent term restoration under the Waxman/Hatch Act, postponing expiration until July 31, 2006. With a six-month pediatric extension, the '909 patent is slated to expire Jan. 31, 2007, according to the "Orange Book."

Although Pfizer conducted clinical trials using the maleate salt version of amlodipine, the company ultimately received approval for the besylate salt form on July 31, 1992.

In December 2001, Reddy's filed a 505(b)(2) application for use of amlodipine maleate in the same indications as Norvasc - treatment of hypertension, chronic stable angina and vasospastic angina. Reddy's certified that manufacture or sale of its product after Feb. 25, 2003 would not infringe the '909 patent.

The Newark court granted Reddy's motion to dismiss Pfizer's infringement lawsuit, agreeing with the generic company's argument that the patent term restoration only extended patent rights for the approved besylate form of the product.

In its appellate brief, Pfizer asserted the patent term extension "applies to the full scope of the claims of the '909 patent, not just to the Norvasc drug product approved by the FDA. The plain language of [35 U.S.C. Section 156] extends 'the term of the patent'...not simply the patent's protection for a specific, limited product."

During arguments before Federal Circuit Judges H. Robert Mayer, Pauline Newman and Alan Lourie, Reddy's attorney Brian Moriarty (Budd Larner Rosenbaum Greenberg & Sade) asserted that approximately 1 mil. compounds could be encompassed by the claims of the '909 patent.

Under Pfizer's interpretation, "its rights to the million compounds would be extended," Moriarty said. "That's a windfall Congress never intended."

Lourie said the million potentially covered compounds are not relevant because Pfizer only seeks coverage for a particular salt of the same active moiety of the approved drug.

"My assumption is that amlodipine maleate will be used as a separate product from amlodipine besylate," Moriarty responded. "The million products are relevant because all million products would follow" Pfizer's broad interpretation of the patent term restoration provisions.

However, Lourie observed that Reddy's 505(b)(2) application relies on studies Pfizer conducted on amlodipine, including amlodipine maleate, as part of its Norvasc development.

"In that sense," Lourie said, amlodipine maleate and amlodipine besylate are "not totally separate products."

Pfizer attorney Glen Nager (Jones Day) asserted that under Reddy's narrow interpretation of the patent term extension provisions, restoration would not protect against small, insubstantial changes to compounds.

"If copiers can do that, they can put products on the market that we invented that have" no therapeutic difference, Nager said.

The court also heard arguments on the appropriate interpretation of Section 156(b), which limits the "rights derived from" a patent during term extension to "any use approved for the product." The statute states the term "product" includes "an approved drug product."

Reddy's argued, and the trial court agreed, that 156(b) limits a patent term extension both to the "use approved" and to the approved product itself.

However, Pfizer said that even if Section 156 limits a patent term extension to the approved product, the approved product here includes amlodipine maleate. Section 156(f) defines a drug product as including "the active ingredient" of a new drug, "including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient."

However, Reddy's said the appeals court previously has rejected the argument that the term "product" in 156(f) means a new active moiety encompassing all salts. "Instead, this court held that the term 'drug product' means 'active ingredient' and not 'active moiety,'" Reddy's brief states.

The significant public policy implications raised in the Norvasc case are reflected in six amicus briefs filed on Pfizer's behalf by the Pharmaceutical Research & Manufacturers of America, Washington Legal Foundation, Merck, Lilly, Wyeth and Takeda.

WLF's brief states the Newark court's "approach legitimizes poaching on patented drug innovation" and "cannot be reconciled with the policy judgment Congress made in promising meaningful patent extensions to pharmaceutical companies that invent and patent new therapeutic agents."

The disputes between Pfizer and Reddy's related to Norvasc are being played out in the regulatory setting as well as in the courtroom. In a citizen petition filed with FDA, Pfizer said Reddy's should be required to independently establish safety and efficacy without relying on data from the Norvasc NDA (² (Also see "Pfizer Norvasc Challenges: Mylan ANDA, Dr. Reddy’s 505(b)(2)" - Pink Sheet, 21 Oct, 2002.), p. 20).

Reddy's application has been "approvable" at FDA since October 2002. Since the drug would not be AB-rated, Reddy's will have to aggressively promote the product. The company is seeking a partner to help market its version of the calcium channel blocker (³ (Also see "Dr. Reddy’s Seeks Partner For Norvasc Salt, Says Pfizer Will Not Delay Launch" - Pink Sheet, 9 Jun, 2003.), p. 7).

If Dr. Reddy's amlodipine maleate were to reach market, it would join Synthon's paroxetine mesylate as examples of different salts of blockbuster drugs gaining approval through the 505(b)(2) route. GlaxoSmithKline markets paroxetine hydrochloride as Paxil (see ⁴ (Also see "Early Paxil Competitor? FDA Approves Synthon’s Paroxetine 505(b)(2)" - Pink Sheet, 14 Jul, 2003.) ).