In Momenta Pharma., Inc. v. Teva Pharma. USA Inc., Nos. 2014-1274, -1277, -1276, and -1278 (Fed. Cir. Nov. 10, 2015) (“Momenta II”), the Federal Circuit found that, pursuant to 35 U.S.C. § 271(g), “made” is limited to steps directly related to manufacturing products and excludes isolated quality control steps. The court also revisited its prior ruling in Momenta Pharma., Inc. v. Amphastar Pharms., Inc., 686 F.3d 1348 (Fed. Cir. 2012) (“Momenta I), and based on the fuller record, decided that post-approval quality control batch testing does not fall within the 35 U.S.C. § 271(e)(1) safe harbor.

This appeal arose from ANDA litigation involving generic versions of Lovenox® (enoxaparin), which is prescribed to prevent blood clots. Momenta I, 686 F.3d at 1349. Enoxaparin is a low molecular weight version of heparin and is produced by breaking the heparin polysaccharide into smaller oligosaccharide fragments. Id. at 1349-50. Unlike traditional small molecule pharmaceuticals, such as penicillin, enoxaparin is not a single molecule but rather a combination of several different molecules. Id. at 1350. This molecular diversity presents an issue for ANDA filers – how to establish bioequivalence to Lovenox®? Id. To address this issue, the FDA identified five “standards for identity” that provide enough information to conclude that a generic enoxaparin is the “same” as Lovenox®. Id. Pursuant to these standards, the FDA required “equivalence in disaccharide building blocks, fragment mapping, and sequence of oligosaccharide species,” and suggested that disaccharide identity could be determined via standard experimental techniques. Id. at 1350-51.

Momenta Pharmaceuticals and Sandoz, Inc., collaborated to bring the first generic enoxaparin to market. Momenta II, slip op. at 4. Momenta is also the assignee of U.S. 7,575,886 (the 886 patent), which relates to “methods and products associated with analyzing and monitoring heterogeneous populations of sulfated polysaccharides,” such as enoxaparin. Id.; the 886 patent at Abstract. Claim 6 is representative:

6. A method for analyzing an enoxaparin sample for the presence or amount of a non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin that included ß-eliminative cleavage with a benzyl ester and depolymerization, comprising:

providing an enoxaparin sample that has been exhaustively digested with two or more heparin degrading enzymes;

using a separation method to determine, in the enoxaparin sample that has been contacted with two or more heparin degrading enzymes, the presence of a structural signature associated with the non naturally occurring sugar associated with peak 9 of FIG. 1 that results from a method of making enoxaparin that includes ß-eliminative cleavage with a benzyl ester and depolymerization; and

making a determination about the enoxaparin sample based upon a comparison of the determination of the presence of a structural signature associated with the non naturally occurring sugar associated with peak 9 to a reference standard for enoxaparin, wherein the determination based upon the comparison to the reference standard regards the quality of the sample,

to thereby analyze the enoxaparin sample.

Momenta alleged that both Teva and Amphastar infringed the 886 patent: Teva, through its manufacturing, analysis, testing, and packaging activities in Italy and subsequent importation into the U.S.; Amphastar, through its domestic manufacturing activities. Momenta II, slip op. at 4-5.

Momenta’s Quality Control Invention Is Not Part of the “Manufacture” of Enoxaparin

Section 271(g) prohibits the unauthorized importation into the United States, or sale or use within the United States, of a “product which is made by a process patented in the United States.” 35 U.S.C. § 271(g) (emphasis added). The billion-dollar question on appeal was whether Teva’s products are “made by” Momenta’s patented process. Id. at 6-7. The Federal Circuit held they are not, affirming the district court’s grant of summary judgment in Teva’s favor. Id. at 12.

“Made,” according to the Federal Circuit, means “manufactured,” i.e., “the creation or transformation of a product, such as by synthesizing, combining components, or giving raw materials new properties.” Id. at 12-13. It does not extend to “testing to determine whether an already-synthesized drug substance possesses existing qualities or properties.” Id. Interestingly, the court noted that “an enoxaparin batch from which the samples were extracted may be selected for incorporation into the finished product. No assertion is made, however, that the enoxaparin samples on which tests are performed are themselves incorporated into the finished product or imported into the United States.” Id. at 9-10 (emphasis added). Query then, whether the outcome would have been different if Momenta’s claims included the additional steps of converting the analyzed enoxaparin samples into a finished dosage form.

Interestingly, the Federal Circuit also concluded that Amphastar’s American-made enoxaparin is not “made by” Momenta’s patented process under Section 271(g). Id. at 12. Section 271(g) is a provision that typically arises when manufacturing activities occur abroad, rather than in the United States. But here, Momenta alleged that Amphastar’s domestic activities also infringed under 35 U.S.C. § 271(g), which makes it an act of infringement to “offer [] to sell” or “sell[]” . . . within the United States a product which is made by a process patented in the United States. Since the Federal Circuit found that the accused products were not “made by” the patented process, the court did “not reach the question of whether that subsection applies if the patented process is practiced domestically rather than abroad.” Id. at fn.3. In his dissent, Judge Dyk expressed that Section 271(g) has no geographical limitation. Id. at dissent fn.1.

Amphastar’s Domestic Use of Momenta’s Quality Control Invention Is Not Protected by the Safe Harbor

With regard to Momenta’s assertions that Amphastar’s American-made enoxaparin infringed the 886 patent under Section 271(a), Amphastar urged that its activities were shielded by 35 U.S.C. § 271(e)(1)’s safe harbor. One may have expected this defense to be successful, since the Federal Circuit denied Momenta’s request for a preliminary injunction against Amphastar in Momenta I for this reason. Id. at 14-15, 17. There, the Federal Circuit decided that the post-approval quality control steps were not “routine” since Amphastar’s ability to continue to sell its product was tied to Amphastar’s submission of quality control information to the FDA. Momenta I, 686 F.3d at 1359-60.

But in revisiting this issue, on a fuller record, the Federal Circuit changed its mind and decided that Amphastar’s activities were not protected by the safe harbor. Momenta II, slip op. at 17. Here, the court stated, “[t]he routine quality control testing of each batch of generic enoxaparin as part of the post-approval, commercial production process is therefore not ‘reasonably related to the development and submission of information’ to the FDA.” Id. Commenting on its prior decision, the Federal Circuit called it “clearly erroneous,” noting that it would result in “manifest injustice.” Id. at 17-18.