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“Therapeutically Effective Amount” Need Not Heal or Cure

August 03, 2006

Decision icon Decision

Last Month at the Federal Circuit - September 2006

Judges: Michel (dissenting-in-part), Clevenger, Schall (author)

[Appealed from: D. Mass., Judge Young]

In Amgen, Inc. v. Hoechst Marion Roussel, Inc., No. 05-1157 (Fed. Cir. Aug. 3, 2006), the Federal Circuit ruled that Amgen, Inc.’s (“Amgen”) claim term “therapeutically effective amount” is not limited to an amount that effectively heals or cures disease. The Federal Circuit vacated the district court’s judgment of invalidity and remanded the case for a determination of whether a cited reference anticipated the claim. The Federal Circuit also reversed the district court’s judgment that the defendant’s accused product infringed under the DOE. Finally, it affirmed the district court’s judgment that Amgen’s method claims were not invalid and were literally infringed.

Amgen is the owner of U.S. Patent Nos. 5,618,698 (“the ’698 patent”), 5,621,080 (“the ’080 patent”), 5,756,349 (“the ’349 patent”), and 5,955,422 (“the ’422 patent”), all directed to a recombinant human erythropoietin, which is an engineered version of a naturally produced protein that stimulates red blood cell production and can be used to treat red blood cell disorders. Hoechst Marion Roussel, Inc. (now Aventis Pharmaceuticals, Inc.) (“HMR”) and Transkaryotic Therapies, Inc. (“TKT”) (collectively “HMR/TKT”) collaborated to develop the recombinant erythropoietin HMR4396.

In 1997, Amgen filed suit for DJ in district court. The resulting proceedings included a Markman hearing, bench trial, Federal Circuit appeal, second Markman hearing, and second bench trial. In the second bench trial, the district court construed a “therapeutically effective amount” of erythropoietin as an amount that not only increased the percentage of blood occupied by red cells (hematocrit) but also healed or cured disease in the class of patients listed in the specification. According to the district court’s construction, Amgen’s claim to a composition comprising a therapeutically effective amount of human erythropoietin was not anticipated by a prior art reference describing the use of naturally produced erythropoietin in an amount too low to heal or cure a patient. The district court also found that HMR/TKT’s HMR4396 comprising 165 amino acids infringed Amgen’s claims to a 166 amino acid erythropoietin under the DOE. Finally, the district court ruled that Amgen’s claims to a method of making recombinant erythropoietin were not invalid and were literally infringed.

On appeal, the Federal Circuit rejected the district court’s narrow claim construction of “therapeutically effective amount,” instead construing it to mean an amount that elicits any biological effect listed in the specification. It cited a statement in the specification that erythropoietin could lack in vivo activity and still possess therapeutic utility as evidence that the patentee did not intend the word “therapy” to limit the scope of its claim to an erythropoietin compound capable of curing a disease. Rather, the words “therapeutically effective” broadly claim a composition with a wide range of biological effects. According to the specification, Amgen’s recombinant erythropoietin possessed all the properties attributed to the body’s natural erythropoietin. Thus, a therapeutically effective amount of recombinant erythopoietin is an amount sufficient to elicit any of the listed effects of natural erythropoietin, including, but not limited to, the power to cure. Nor is it limited to require any one particular biological effect, such as an increase in hemoglobin. Accordingly, the district court was ordered to use this revised claim construction on remand. It was also ordered to evaluate a prior art reference report of naturally produced erythropoietin eliciting certain biological effects but failing to increase the hematocrits or heal the recipient patients, to determine whether it anticipated claim 1 of the ’422 patent under the new claim construction.

The Federal Circuit next reversed the district court’s holding that Amgen infringed the ’080 patent under the DOE, concluding that prosecution history estoppel prevented Amgen from asserting that its claims to an erythropoietin having 166 amino acids encompassed an erythropoietin of 165 amino acids. Amgen amended claims broadly encompassing an isolated human erythropoietin to read only on an erythropoietin having 166 amino acids. The Federal Circuit did not consider the requirement for 166 amino acids to be tangential to a 165 amino acid equivalent. Rather, it considered the amendment vital to avoiding a double patenting rejection. Amgen’s argument that the sole reason for the amendment was to limit the claim to human erythropoietin was rejected because the amendment discontinued using the term “human” in favor of making reference to a particular sequence of 166 amino acids.

Lastly, the Federal Circuit affirmed the holding of the district court that Amgen’s method claims to producing erythropoietin were not invalidated by a prior art reference because the reference was not enabled. The reference disclosed a method of making erythropoietin by fusing human erythropoietin-producing cells with a human cell line. Basing its conclusion on the testimony of several scientists experienced in the field, the court found that the reference did not disclose the cells necessary to perform the method, teach the selection of the fusion products, nor teach the purification of erythropoietin from the fused cells.

Judge Michel wrote in dissent that Amgen’s claim to a “therapeutically effective amount” of erythropoietin should not be invalidated by a reference to a prior art compound capable of eliciting biological activity but incapable of healing or curing. Reasoning that merely eliciting a biological effect is not the same as demonstrating therapeutic effectiveness, he complemented the district court’s reasoning that a “therapeutically effective amount” means a quantity that produces a result that in and of itself helps to heal or cure. He also cited the convention in the pharmaceutical arts to use the term to mean that a compound is useful in treating disease. He contended that the part of the specification cited by the majority for the proposition that a product can be therapeutically useful without having in vivo activity referred only to erythropoietin analogs, not to the claimed erythropoietin.