Legal Forum: Drug Product, Active Ingredient, and Patent Term: A Recipe for Confusion

The Drug Price Competition and Patent Term Restoration Act (1984), more commonly known as the Hatch-Waxman Act (herein "the Act"), seeks to give a patent owner at least partial restoration of the patent term period lost while obtaining regulatory approval for a patented article or method, typically a drug, medical device, or therapeutic method.

Judy M. Mohr, PhD

Limitations on patent-term extension under the Act are neatly summarized by the "rule of ones:" one patent extension per product, one patent extension per patent, and one product per patent extension.¹ "One patent extension per product" refers to the statutory requirements that no other patent has been extended for the product,² and that "in no event shall more than one patent be extended for the same regulatory review period of any product."³ "One patent extension per patent" reflects the requirement that the term of the patent has never been extended."⁴ The third rule, "one product per patent extension," derives from the goal of the Act to allow a restoration of patent term only for the product for which regulatory approval was sought. That is, only the product that served as the basis of the extension is exclusively covered by the patent during its extended term.

These rules adequately address most, but not all, patent-term extension issues. This article addresses one of the "ambiguous" outcomes under the rules of one, and how the courts are currently dealing with this issue. The question raised is this: If marketing approval for a particular form of a drug is granted, and the term of patent covering that form of the drug is extended under the Act, is it possible to extend the term of a patent on a different form of the drug, e.g., a different salt or free-base, or free-acid form of the same drug?

ADDRESSING THE QUESTION

This question was considered by the Court of Appeals for the Federal Circuit in Glaxo Operations UK Limited v. Quigg.⁵ Glaxo (now GlaxoSmithKline) sought a patent-term extension for cefuroxime axetil, which had been approved for marketing as a broad spectrum oral antibiotic under the trade name Ceftin. Cefuroxime sodium had been previously approved as an injectable antibiotic, marketed as both Zinacef and Kefurox. Glaxo's patent-term extension for cefuroxime axetil, an ester of cefuroxime, was denied by the US Patent and Trademark Office on the grounds that it was not the initial permitted commercial marketing or use of the product, a violation of the "one patent extension per product" rule. Glaxo argued that cefuroxime axetil is not the same "drug product" as cefuroxime sodium. The court agreed with Glaxo, reasoning that (a) the already approved drug was cefuroxime sodium; (b) a "drug product" under the Act means an "active ingredient of a new drug....including any salt or ester of the active ingredient" (35 U.S.C. § 156 (f)(2)); and (c) cefuroxime axetil is not a salt or ester of the cefuroxime sodium. In other words, cefuroxime axetil was not the same "active ingredient" as the cefuroxime sodium because it was not "a salt or ester" of cefuroxime sodium. This result is not illogical, because different drug forms could be considered to be different "drug products" based on differing pharmacokinetics and, sometimes, pharmacodynamics. That is, the two drugs might be considered to be different "active ingredients." The court's reasoning in Glaxo is not based on any demonstrated distinction between the two compounds at issue. Rather, it appears to rely on the misunderstanding that sodium salt of an active anionic compound cannot have an ester form. This reasoning would lead to diametrically opposed results, depending on whether the drug that was approved originally, was in a salt or acid form.

This problematic reasoning was recognized by the Court of Appeals for the District of Columbia in another case involving Abbott and dealing with the definition of "active ingredient."⁷ The issue in Abbott centered on the period of market exclusivity granted for a new drug under 21 U.S.C. § 355(j)(4),⁸ which provided for a 10-year period of market exclusivity for a new "active ingredient." Valproic acid had been previously approved for marketing and was sold as Depakene.

Abbott argued that its novel disodium valproic was a new "active ingredient," and therefore entitled to 10-year market exclusivity. Because the federal market exclusivity provisions are part of the Act, but codified in different chapters of the US code, one might expect that the meaning of "active ingredient" should be consistent throughout the Act. However, the Abbott court, recognizing the problem that was engendered by reasoning in Glaxo, arrived at the opposite conclusion, ruling that "active ingredient" in the Act means "active moiety."

Had this definition of "active ingredient" been applied in the Glaxo case, the court could easily have concluded that the active ingredient, i.e., the active moiety, in cefuroxime axetil was the same as that in cefuroxime sodium, thus precluding patent term extension on the axetil form of the compound.

GOING FORWARD

In summary, under the holding of the Glaxo court, a drug product based on a new salt or ester of a previously approved salt or ester drug product, may be eligible for a patent-term extension. Under the reasoning in Abbott, approval of a drug product in any form would seem to preclude patent-term extension on a subsequent product based on any other form of the same drug, that is, a drug having the same active moiety. However, to the extent the Glaxo decision is based on a misunderstanding of chemical forms of drug, it is likely to carry less validity in the future.

This shift toward the Abbott decision is reflected in Pfizer, Inc., v. Dr. Reddy's Laboratories, Ltd.⁹ The Pfizer court relied on the earlier Abbott decision and agreed that active ingredient means "active moiety," for purposes of determining what "product" is covered by a patent term extension. The Pfizer court ruled that a previous product approval and patent-term extension on a particular salt form of a drug encompassed alternative salt and ester forms of the drug.

Until this issue is resolved by the courts, it may nonetheless be prudent for a drug manufacturer in this situation to seek patent-term extension, arguing the reasoning derived from the Glaxo case. An applicant for a patent term extension should also search for arguments to demonstrate that the compounds in question are not the same "active moieties."

Judy M. Mohr, Ph.D. Perkins Coie, LLP, 101 Jefferson Drive Menlo Park, CA 94025, 650.838.4402,fax 650.838.4350, jmohr@perkinscoie.com

REFERENCES

1. Cardiac Pacemakers v. St. Jude Medical Inc., WL 483973 (S.D. Ind. 2001).

2. 35 U.S.C. § 156(a)(5).

3. 35 U.S.C. § 156(c)(4).

4. 35 U.S.C. § 156(a)(2).

5. Glaxo Operations UK Limited v. Quigg (894 F.2d 392 (Fed. Cir. 1990)).

6. 35 U.S.C. § 156 (f)(2).

7. Abbott Laboratories v. Young, 920 F.2d 989 (U.S. App. D.C. 1990).

8. 21 U.S.C. § 355(j)(4).

9. Pfizer Inc. v. Dr. Reddy's Laboratories, Ltd., 359 F.3d 1361 (Fed. Cir. 2004).