May 2011

Claims to a Method of Detecting a Genetic Disorder Not Adequately Described Where the Gene Sequence or Its Specific Disease-Causing Mutations Were Not Disclosed
Mukta Jhalani

In Billups-Rothenberg, Inc. v. Associated Regional & University Pathologists, Inc., No. 10-1401 (Fed. Cir. Apr. 29, 2011), the Federal Circuit affirmed the district court’s SJ findings that the asserted claims of U.S. Patent No. 5,674,681 (“the ’681 patent”) were invalid for lack of written description and that the asserted claims of U.S. Patent No. 6,355,425 (“the ’425 patent”) were invalid as anticipated by the prior art.

The ’681 and ’425 patents describe genetic tests for a disorder characterized by excessive iron absorption by the body, known as Type I hereditary hemochromatosis (“hemochromatosis”).  Deoxyribonucleic acid (“DNA”) is composed of sequences of four nucleotides arranged in functional units, known as genes, that contain hereditary information.  DNA is packaged into structures known as chromosomes.  Mutations that alter a sequence of nucleotides may affect the structure or function of the protein encoded by the gene.  Hemochromatosis is caused by specific genetic mutations in the High Fe (“HFE”) gene that result in the formation of a mutated HFE protein that causes an increase in iron absorption from the gut.  The claims in the patents-in-suit are directed to the detection of one or both of two distinct mutations in the HFE gene known as C282Y and S65C.

In 1994, Billups-Rothenberg, Inc. (“Billups”) filed the application for the ’681 patent, identifying the human chromosomal location of the gene responsible for hemochromatosis.  The claims-at-issue covered methods of detecting mutations responsible for hemochromatosis even though the ’681 patent did not identify any disease-causing mutations.  Additionally, scientists working at Billups during that time were unable to isolate the hemochromatosis gene or any mutations of the gene.

In 1996, scientists unaffiliated with Billups isolated and sequenced the hemochromatosis gene and published their results.  Their research resulted in several patents, including U.S. Patent No. 6,025,130 (“the ’130 patent”).  The ’130 patent disclosed the exact genetic sequences for the three mutations at issue in this case:  C282Y, H63D, and S65C.  It also described genetic tests for hemochromatosis utilizing the mutations identified in the ’130 patent.  The ’130 patent was assigned to Bio-Rad Laboratories, Inc. (“Bio-Rad”) and licensed to Associated Regional and University Pathologists, Inc. (“ARUP”).  ARUP continued to search for the hemochromatosis gene and developed an assay to detect the C282Y, H63D, and S65C mutations.

On March 26, 1999, the Billups researchers, having used the genetic sequences disclosed in the ’130 patent, filed the application that issued as the ’425 patent.  The ’425 patent claimed a method for diagnosing an iron disorder by testing for genetic mutations including S65C and concluded that the S65C mutation could be used to diagnose hemochromatosis. 

In 2009, Billups sued ARUP and Bio-Rad for infringement of the ’681 and ’425 patents.  The parties filed cross-motions for SJ after a Markman hearing.  The district court found the ’681 patent invalid for lack of an adequate written description because the DNA sequence of the hemochromatosis gene and/or sequence of the C282Y mutation were not expressly disclosed in the ’681 patent.  In light of its finding on written description, the district court did not rule on ARUP and Bio-Rad’s lack of enablement arguments.  Additionally, the district court found the ’425 patent invalid as anticipated by the ’130 patent.  Billups appealed.

The Federal Circuit agreed that the ’681 patent lacked written description support.  Specifically, the ’681 patent claims a test for mutations, yet it was undisputed that neither the hemochromatosis gene sequence nor any specific mutations within that gene were disclosed.  Additionally, the disclosure did not provide the exact location of the mutation in the gene.  The Court rejected Billups argument that the claimed invention was adequately described:  “Given the lack of knowledge of sequences for the hemochromatosis gene and its mutations in the field, the limited extent and content of the prior art, and the immaturity and unpredictability of the science when the ’681 patent was filed, Billups cannot satisfy the written description requirement merely through references to later-acquired knowledge.”  Slip op. at 11.

The Court noted that the ’681 patent claims cover the identification of a genus of unknown genetic mutations.  Thus, the patent “must set forth ‘either a representative number of species falling within the scope of the genus or structural features common to the members of the genus.’”  Id. at 12 (quoting Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010) (en banc)).  The ’681 patent, however, did not identify even a single species that satisfies the claims.  Further, the Federal Circuit agreed with the district court that “the art did not establish a correlation between structure and function because the ‘[p]atentee’s general location disclosure is too imprecise to constitute structural features necessary to meet the written description requirement.’”  Id. (alteration in original) (citation omitted).  Rather, the specification “contains only functional, not structural, characteristics of the predicted mutations.”  Id. (citation omitted).  Thus, the district court properly granted SJ of invalidity for lack of adequate written description and was within its discretion to decline to rule on the nonenablement.

The Federal Circuit also agreed that the ’425 patent was invalid as anticipated by the ’130 patent.  Specifically, the ’130 patent was 35 U.S.C. § 102(e) prior art because it was filed nearly three years before the ’425 patent.  The ’130 patent disclosed the genetic sequence of the S65C mutation and described a genetic assay for detecting one or more of the C282Y, H63D, and S65C mutations.  The Court acknowledged, as Billups had argued, that the ’130 patent specification expresses uncertainty regarding the utility of the S65C mutation in the potential diagnosis of hemochromatosis.  The Federal Circuit reiterated, however, that “[a] reference is no less anticipatory if, after disclosing the invention, the reference then disparages it.”  Id. at 15 (quoting Celeritas Techs., Ltd. v. Rockwell Int’l Corp., 150 F.3d 1354, 1361 (Fed. Cir. 1998)).  Further, “whether a reference ‘teaches away’ from the invention is inapplicable to an anticipation analysis.”  Id. (citation omitted).  Thus, the Court found that the ’130 patent anticipated the ’425 patent’s claims because the ’130 patent disclosed at least one diagnostic test for hemochromatosis that included identification of the S65C mutation, even though the ’130 patent qualified its disclosure with the observation that the mutation “may only be a polymorphic variant.”  Id. (citation omitted).

Finally, the Federal Circuit noted that Billups conceded during oral argument that it had waived its argument that the ’130 patent was not enabled and hence could not be anticipatory.  The Court, however, noted that, even if Billups’s argument were not waived, a district court presumes enablement of material in a prior art patent and that Billups failed to present persuasive evidence of nonenablement to the district court.

Accordingly, the Federal Circuit found the asserted claims of the ’681 patent invalid for lack of written description and the asserted claims of the ’425 patent invalid as anticipated by the ’130 patent.