In Billups-Rothenberg, Inc. v. Associated Regional And University Pathologists, Inc., the Federal Circuit affirmed the district court’s grant of summary judgment of invalidity based on a lack of written description. The claims at issue were directed to methods of diagnosing a disease by detecting a specific genetic mutation associated with that disease, but the patent did not disclose any such genetic mutation.

The Patent At Issue

The patent at issue relates to a genetic test for Type I hereditary hemochromatosis, which is an iron disorder that leads to excessive iron absorption. The disorder is caused by specific mutations in a gene involved in regulating iron absorption, known as the High Fe (HFE) gene. The specific mutations now are identified as C282Y and S65C.

U.S. Patent 5,674,681 issued with two independent claims, but only the subject matter of claim 2 was at issue:

2. A method to identify an individual having or predisposed to having hemochromatosis, comprising the steps of:
a) providing from the individual a sample containing a gene encoding a nonclassical MHC class I heavy chain, and
b) detecting a mutation in said gene, which mutation results in the reduced ability of said heavy chain to associate with said ß2 microglobulin, wherein the presence of said mutation identifies said individual as having or predisposed to having hemochromatosis.

Much of the disclosure of the ‘681 patent is directed to a different invention:

The present invention provides a substantially purified carbohydrate ligand that specifically binds to a leczyme. In addition, the invention provides methods to identify a carbohydrate ligand that specifically binds to a leczyme or a leczyme that specifically binds to a carbohydrate ligand. The invention further provides methods to identify a peptide that binds to the carbohydrate ligand binding-site of a leczyme.

With regard to the claimed subject matter, the patent teaches:

Hemochromatosis results from enhanced absorption of iron from the GI tract by active transport but the underlying metabolic defect is currently unknown. Identification of the genes responsible for the absorption of iron, and developing an animal model in which iron overload is due to active enhanced absorption of iron from the GI tract, would greatly facilitate understanding hemochromatosis and increase knowledge about the general mechanisms of iron metabolism. The present invention provides the results from a new animal model and data from humans that indicate a role for an MHC-encoded leczyme in the pathogenesis of hemochromatosis.

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Hemochromatosis is an autosomal recessive disease in which the responsible gene(s) is linked to the A locus of the human MHC (HLA complex), located on human chromosome 6 (Simon and Brissot, Hepatol., 6:116-124 (1988)). Linkage to human HLA-A3 has been documented in approximately 73% of cases. However, other genetic loci also have been implicated, especially in African (Gorduke et al., N. Engl. J. Med., 326:95-100 (1992)) and African-American populations (Barton et al., Blood, 85:95a (1993)).

Hemochromatosis is the most common genetic malady in humans far exceeding cystic fibrosis, phenylketonuria and muscular dystrophy combined (Leggett et al., Clin. Chem., 36:1350-1355 (1990)). One explanation for the high incidence of this genetic disease may be that results from different mutations in multiple linked genes that produces a similar phenotype. Hemochromatosis occurs most frequently in populations of European origin with a frequency in homozygotes and heterozygotes of approximately 0.3 and 13%, respectively.

Several markers, including the recently described D6S105, have been identified in the human MHC locus and have narrowed the genomic location of the hemochromatosis gene to within 1 centimorgan of the A locus (Jazwinska et al., Am. J. Hum. Genet., 53:347-352 (1993)), and possibly centromeric to HLA-F (Gasparini, et al., Hum. Mol. Genet., 5:571-576 (1993)). Others have reported candidate (HC) genes located 20-200 kb telomeric to HLA-A (el Kahloun et al., Hum. Mol. Genet., 2:55-60 (1993)). While several of these candidate genes were thought to be single copy, three of the genes, termed HCG II, IV and VII, were found to be multicopy genes. Thus, despite the advances made in determining the location of the HC gene, it has not yet been isolated.

The District Court Decision

Billups sued ARUP and Bio-Rad Laboratories, Inc. for infringing the ‘681 patent by “providing and/or using diagnostic assays or kits for detecting hemochromatosis” associated with one or both of the C282Y and S65C mutations. On cross-motions for summary judgment, the district court found that the ‘681 patent was invalid for failing to satisfy the written description requirement of 35 USC § 112. As summarized in the Federal Circuit decision, the district court noted the following undisputed facts:

  • “The DNA sequence of the hemochromatosis gene and/or sequence of the C282Y mutation were not expressly specified in the ’681 patent.”
  • “[N]o species of the genus of DNA mutations, the presence of which would identify an individual as having or being predisposed to having hemochromatosis, were disclosed in the ’681 patent specification.”
  • “Describing the structure of the resulting protein is not the same as describing the structure of the DNA and its mutations. The invention claimed in the ’681 patent is a method to test for a DNA mutation, not a test for a defective protein.”

The district court noted that the patent “has merely directed the person of ordinary skill in the art to a general location of a mutation on a chromosome and suggested that the mutation may be found in that vicinity,” and found that the asserted claims were invalid for lack of written description.

The Federal Circuit Decision

As expected, the Federal Circuit decision quotes heavily from its 2010 en banc decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. For example, the court notes that the written description requirement “limits patent protection to those who actually perform the difficult work of ‘invention’—that is, conceive of and complete the final invention.” The court also cites its 1993 decision in Fiers v. Revel for the proposition that the written description requirement ensures that inventors do not “preempt the future before it arrives.”

Billups made three main arguments, each of which the Federal Circuit rejected.

  1. Billups argued that the “disclosure of the mutation’s general location somewhere ‘within less than a 300 base pair region of a defined exon of a well studied multi-gene family,’ combined with the knowledge that existed at the time of filing” was sufficient to establish “possession” of the claimed invention. However, the Federal Circuit emphasized that the specification “disclose[s] neither the hemochromatosis gene sequence nor any specific mutations within that gene.”
  2. Billups argued that “knowledge outside the patent, including the subsequent discovery of [the] C282Y [mutation]” adequately described the “envisioned” mutations. The Federal Circuit rejected this argument, citing Fiers for the proposition that the written description requirement cannot be satisfied “merely through reference to later-acquired knowledge.”
  3. Billups argued that the written description requirement was satisfied by the combined disclosure of structure (approximate location of the mutation) and function. But, the district court had found that the “general location disclosure is too imprecise to constitute structural features necessary to meet the written description requirement,” and the Federal Circuit agreed.

The Federal Circuit also noted that the patent in effect claimed “a genus of unknown genetic mutations” without “identify[ing] even a single species that satisfies the claims.” The court stated:

Billups did not possess a genetic mutation useful for diagnosing hemochromatosis when it filed its patent application in December of 1994. The ’681 patent merely represents Billups’s research plan.

The Other Asserted Patent

Billups also had asserted another patent that does set forth specific mutations, U.S. Patent 6,355,425. That patent was held invalid over prior art, however, because the mutations at issue were disclosed in an intervening patent.

Rushing to the Patent Office?

A case like this underscores the difficulty of deciding when to file a patent application. File “too early” in the development process and your patent may be at risk of invalidation under the written description or enablement requirements. File “too late” and you may lose out to a competitor working in the same field.

When the decision to file is being made, the calculation can be complicated. Compliance with the written description requirement is a fact-intensive inquiry that involves factors beyond the four corners of the patent document, including the state of the art and the complexity of the technology at issue. Moreover, written description jurisprudence is evolving, and patents face more scrutiny under this statute than they have previously. In this decision, the Federal Circuit appears to indicate that it will be looking for at least one specific embodiment (species) that falls within the scope of any generic (genus) claim, regardless of whether the claims at issue are directed to a product or a method.