calvinball.gifWhat happens when a brand name drug company asserts that a patent covers its drug and then pulls it out from the Orange Book? You fight to get it back in, that’s what.

In August, Teva Pharmaceuticals USA submitted a Citizen Petition pursuant to section 505 of the Food, Drug, and Cosmetic Act (FDCA) asking the FDA to do just that.

The FDA’s official Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book“) listed two patents as claiming Risperdal® tablets: U.S. Patent No. 4,804,663, which was set to expire on December 29, 2007, and U.S. Patent No. 5,158,952 (“the ‘952 patent”), which will expire on October 27, 2009.  Risperidone is an antipsychotic medication sold by Janssen Pharmaceutica (a subsidiary of Johnson & Johnson) under the trade-name Risperdal®.

Teva submitted an original Abbreviated New Drug Application (ANDA) seeking approval to market generic risperidone tablets. Because the Orange Book listed both the ‘663 and ‘952 patents for Risperdal® tablets, Teva was required to certify as to both patents.

Teva filed a certification under § 355(j)(2)(A)(vii)(III) (“Paragraph III certification”) as to the ‘663 patent, which is set to expire on December 29, 2007, and a certification under § 355(j)(2)(A)(vii)(IV) (“Paragraph IV certification”) as to the ‘952 patent, asserting that the patent was invalid or would not be infringed by Teva’s generic risperidone tablets.

Ordinarily, Teva would be entitled to 180 days of marketing exclusivity for its generic risperidone tablets as a result of its paragraph IV certification to the ‘952 patent. That’s because the ‘952 patent appeared in the official Orange Book when it originally filed – that meant that Teva was required to submit a certification to that patent at the time it submitted its ANDA for generic risperidone drug products. Teva then became the first company to submit a paragraph IV certification to any of the listed patents claiming Risperdal®.

On October 12, 2001, FDA notified Teva that it had “delisted” the ‘952 patent from the Orange Book (even though it continued to appear in the official Orange Book at that time) It also informed Teva that it would not accept Teva’s ANDA for filing unless Teva modified its patent certification to reflect that the ‘952 patent was no longer listed as claiming the reference drug product.

In November 2006, the D.C. Circuit ruled that the plain text of the FDCA prevented the FDA from effectuating the delisting of a patent following the submission of a paragraph IV certification as to that patent. Ranbaxy Laboratories Ltd. v. Leavitt, 469 F.3d 120, 125-26 (D.C. Cir. 2006). The court struck down the FDA’s practice because it “changed the incentive structure adopted by Congress,” by “depriving the generic applicant of a period of marketing exclusivity” after the generic manufacturer had expended significant resources in developing a non-infringing generic substitute and undertaken the risk of infringing the patent by filing a paragraph IV certification.

Teva then filed a Citizen’s Petition with the FDA arguing that the FDCA entitles Teva to a 180-day period of first-filer exclusivity for generic Risperdal® tablets since it was the first generic manufacturer to file an ANDA for generic risperidone tablets containing a paragraph IV certification as to the ‘952 patent.

Under 21 U.S.C. § 355(j)(5)(B)(iv) (2002), the earliest any subsequently-filed paragraph IV ANDA can be approved is “one hundred and eighty days after” Teva first commercially markets its generic risperidone tablets or the date of a court decision holding the ‘952 patent to be invalid or not infringed.

Teva argued that both FDA regulations and case law make clear that the agency does not adjudicate questions of patent law; instead, it plays only a ministerial role in maintaining the Orange Book. As a result, where a patent remains listed for a particular drug in the official Orange Book, a generic applicant has no choice but to believe that the NDA holder is continuing to assert that patent as claiming the listed drug.

Thus, at the time of its ANDA submission in August 2001, Teva was required to submit a certification to the ‘952 patent. Teva now wants its 180-exclusivity for these drug products.

The question here is whether or not a brand manufacturer can game the system by delisting a patent after the submission of a paragraph IV certification and without notice, forcing generic manufacturers to invest resources and assume the risk of patent litigation without any guarantee of the 180-day exclusivity reward.

The FDA wrote back a nice note to Teva:

We have carefully reviewed your Petition and have concluded that the ‘952 patent was delisted before Teva submitted ANDA 76-228 to FDA. For the reasons described in further detail in this Response, we deny your request that FDA relist the ‘952 patent. As Teva’s ANDA did not contain a paragraph IV certification for a listed patent, and Teva did not provide the required notice of such certification to the holder of the NDA for the reference listed drug and each owner of the listed patent, Teva would not be eligible for 180-day exclusivity pursuant to section 505(j)(5)(B)(iv) of the Act for its pending ANDA 76-228.

Like a game of Calvinball*, since the FDA had itself forced Teva to remove the paragraph IV certification or it wouldn’t accept the ANDA, the FDA now claims that Teva’s out of luck because it did, in fact, take out the certification.


It probably wouldn’t take a law degree to guess that Teva has filed a lawsuit in federal court to try to get the Petition granted. Johnson & Johnson’s sales of antipsychotics in the U.S. were more than $2.7 billion last year with Risperdal accounting for a large part of that amount. A generic can make quite a bit in just 180 days.

Stay tuned.

Teva vs. FDA Complaint

[*Note: Under the Official Rules of Calvinball, Rule 1.2. states: “Any player may declare a new rule at any point in the game (Figure 1.2). The player may do this audibly or silently depending on what zone (Refer to Rule 1.5) the player is in.”]

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  1. Loved that piece, very exciting developments.

  2. Like your disclaimer too!

  3. J&J destroyed themselves on this more. With only one player in the game, price of the drug stays relatively constant, and you can argue with MD’s to DAW it. With many players in the game, say good bye to the Brand completely.