Supreme Court Unanimously Rules for Generic Manufacturers in Improper Patent Listing Case

By Charles Pierce

In Caraco Pharmaceutical Laboratories, Ltd. v. Novo Nordisk A/S, 566 U.S. ___ (2012), the Supreme Court unanimously clarified the prerequisites of 21 U.S.C. §355(j)(5)(C)(ii)(I) counterclaims seeking to correct or delete patent information that a name-brand pharmaceuticals manufacturer submits to the FDA.

Repaglinide is a drug that has been approved by the FDA for the treatment of diabetes.  The FDA approved three methods: repaglinide alone, repaglinide in combination with metformin, and repaglinide in combination with thiazolidinediones.  The compound was covered by the ‘035 patent that Novo had owned, but the patent had expired in 2009.  Novo currently owns the ‘358 patent, a method-of-use patent which claims “a method for treating [diabetes by] administering . . . repaglinide in combination with metformin.”

Generic drug makers, rather than submit a new drug application (NDA), may submit an abbreviated new drug application (ANDA) that piggy back on the brand’s NDA.  Following the expiration of the ‘035 patent, Caraco filed such an ANDA seeking permission to market a generic version of repaglinide alone and repaglinide in combination with thiazolidinediones for the treatment of diabetes.  Before the FDA granted approval, Novo changed its use code for the ‘358 patent to cover all methods of using repaglinidine.  Caraco then filed a certification stating that the ‘358 patent would not be infringed, and Novo treated this as an act of infringement and sued.  Caraco filed a counterclaim under § 355.

21 U.S.C. §355(j)(5)(C)(ii)(I) states that when sued for infringement, an ANDA applicant may:

“Assert a counterclaim seeking an order requiring the [brand] to correct or delete the patent information submitted by the [brand] under subsection (b) or (c) [of §355] on the ground that the patent does not claim either –

(aa) the drug for which the [brand’s NDA] was approved; or

(bb) an approved method of using the drug.”

The parties disagreed on the meaning of the phrase “on the ground that the patent does not claim . . .  an approved method of using the drug.”  Novo argued that this should mean that the only time a counterclaim is allowed is when the patent does not claim any approved method of using the drug.  Caraco argued that instead, a counterclaim was allowed when the ANDA applicant applies for a method of using the drug not covered by the patent.  The Supreme Court agreed with Caraco.

The Supreme Court first examined the statutory context and noted that the statute contemplates that a single patented use should not prevent an ANDA from being approved.  By Novo’s reading, a patent claiming a single method of use would be sufficient to deny both FDA approval and a cause of action to ANDA applicants seeking to market the drug for unrelated uses.  Finding this result to be contrary to the statutory intention, the Court ruled for Caraco’s interpretation.

Novo also argued that Caraco’s counterclaim should fail because use codes are not patent information submitted under subsections (b) or (c) for the purposes of the statute.  The Supreme Court again disagreed with Novo.  First, the Court ruled that a use code does qualify as patent information because it describes the method of use claimed in a patent.  Use codes are required under 21 CFR §314.53 and when issuing §314.53, the FDA noted that its authority stemmed from 21 U.S.C. §355.  Because of this, the Court then decided that subsections (b) or (c), which require an NDA applicant to submit the patent number and expiration date of any patent claiming the drug or its method of use, cover use codes.  The Supreme Court also noted that if a counterclaim in such a case was not allowed, than the term “correct” in “assert a counterclaim seeking an order requiring the [brand] to correct or delete the patent information” would be read out of §355(j)(5)(C)(ii)(I).  Thus, the Court ruled that use codes are patent information submitted under subsections (b) or (c).

Finally, the Court rejected Novo’s legislative history arguments.  Novo first argued that Caraco’s interpretation of §355 would resurrect a scheme rejected by Congress.  A 2002 bill had sought to require brands to file patent information, and allow generic companies to bring actions to correct such information.  The bill failed, but the Supreme Court here declined to view the failure as a Congressional rejection of the requirement, noting that bills may be proposed and rejected for any number of reasons.

The Supreme Court then rejected Novo’s final argument – that the counterclaim was established only in response to the Federal Circuit’s decision in Mylan Pharmaceuticals, Inc. v. Thompson, 267 F. 3d 1323 (Fed. Cir. 2001).  In Mylan, the Federal Circuit had decided that no action to delist an improperly listed patent from the Orange Book was available.  The Court noted that even assuming that Congress was responding to Mylan, the situation presented in this case was similar to that in Mylan: an unrelated drug patent blocked FDA approval for a generic manufacturer.  The Supreme Court unanimously ruled for Caraco, deciding that a cause of action exists for generic manufacturers when the brand lists a method-of-use patent that does not cover a method of use for which the generic manufacturer seeks FDA approval.

Federal Circuit Defines Language of 35 U.S.C. § 271(e)(2) in a Hatch-Waxman Controversy

By Kevin M. Repper

In the case of AstraZeneca Pharmaceuticals LP v. Apotex Corp., No. 2011-1182 (Fed. Cir. 2012), Astrazeneca holds the rights to three patents related to the drug rosuvastatin calcium. Two of the three patents involve methods of using rosuvastatin compounds. One of which is a method of treating heterozygous damilial hypercholesterolemia (HeFH) and the other is a method of lowering cardiovascular disease risk for individuals who have normal cholesterol levels but demonstrate elevated circulating C-reactive protein (CRP). The method of use patents expire in 2021 and 2018, respectively.

Apotex, a generic pharmaceutical manufacturer, filed an Abbreviated New Drug Applications (ANDA) with the FDA seeking to market generic rosuvastatin for treating hypercholesterolemia (HoFH) and hypertriglycerdemia while omitting or “carving out” patented indications directed towards the treatment of HeFH and elevated CRP. Under the Hatch-Waxman Act, the filed ANDA must provide a list of all the related patents and if the method of use patents do not claim a use for which the applicant is seeking approval, an applicant may instead submit a statement under 21 U.S.C. § 355(j)(2)(A)(viii) averring that the ANDA excludes all uses claimed in the patent (Section viii). Apotex properly submitted the Section viii statements regarding Astrazeneca’s method patents.

Astrazeneca brought an action against Apotex alleging that Apotex’s ANDAs, as filed, violated § 271(e)(2) because the use of the drug is claimed in AstraZeneca’s method patents. According to § 271(e)(2),  “it shall be an act of infringement to submit an application…for a drug claimed in a patent or the use of which is claimed in a patent…if the purpose of such submission is to obtain approval under such Act to engage in the commercial manufacture, use, or sale of a drug…claimed in a patent of the use of which is claimed in a patent before the expiration of such patent.” Astrazeneca argued that because their method patents claim any use of the drug, Apotex’s filed ANDA falls within the meaning of § 271(e)(2) and has infringed on their patents.

However, the court took a different stance. The court understood the term “use” from § 271(e)(2) to mean “the use listed in the ANDA.” Accordingly, the court held that it is not necessarily an act of infringement under § 271(e)(2) to submit an ANDA for a drug if just any use of that drug is claimed in a patent; rather, infringement of method claims under § 271(e)(2) requires filing an ANDA wherein at least one “use” listed in the ANDA is claimed in a patent. The court concluded that there can be no cause of action for infringement of a method of use unless the accused ANDA actually seeks approval for a patented indication.

An obvious solution for patent holders is to patent the drug itself. Astra has a patent that claims rosuvastatin compounds and pharmaceutical compositions containing such compounds, however the patent was due to expire years prior to the expiration of the method patents. Also, Apotex is challenging the validity of the composition patent in another co-pending litigation. Other solutions may include determining as many methods of treatment for as many diseases as you can and patenting those methods. This however takes a lot of time and a lot of resources.

Another possible option would be to patent the method of what the drug actually does in the body in addition to the disease that the drug treats. For example, rosuvastatin calcium serves to reduce circulating cholesterol by competitively inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase. A patentable method claim of rosuvastatin calcium could have been a method of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase.  This method claim would likely be broad enough to cover most methods of treatment of any particular disease, especially if the diseases were listed the specification. Therefore, the court may have ruled that the use was in fact covered by the claims.

Feature Comment: Building a Solid IP Portfolio – Strategies for Innovator Pharmaceutical Companies

By John K. Weatherspoon, PhD[1]

The importance of having valid, enforceable patent protection was a key theme discussed at the recent Life Sciences Summit held in Long Island, NY, from September 22-23, 2010.   With over 400 attendees at the summit, primarily from the pharmaceutical and biotechnology industries, there was extensive discussion of having solid Intellectual Property (IP) protection which is critical especially for commercializing new therapeutics.  By “solid” IP protection, and in the case of patent protection, this is intended to refer to patents that are ultimately deemed both valid and enforceable. With representatives from large, midsize and emerging biopharmaceutical companies present at the summit, there was particular interest in the importance of IP in the commercialization of new therapeutics, including new pharmaceutical products or “Active Pharmaceutical Ingredients” (APIs).  The importance of solid IP protection can’t be emphasized enough, especially in today’s challenging economic climate.  In the case of emerging biopharmaceutical companies seeking investor funding, a solid IP portfolio is essential.  Also, as discussed at the recent Life Sciences Summit, there are many instances where a major innovator pharmaceutical company seeks to in-license or acquire the IP of a target company, in order to expand its product portfolio. Continue reading