In Genetic Technologies (GTG), the U.S. Court of Appeals for the Federal Circuit (CAFC) held the line in the patent eligibility saga in the field of biotechnology. GTG asserted U.S. Patent No. 5,612,179 against Merial and Bristol Myers. The ‘179 patent claims a method of genetic analysis based on the discovery that the presence of certain DNA sequences in coding regions (exons) of genes are correlated with the presence of certain DNA sequences in non-coding regions (introns) of the genome. In other words, a specified exon sequence is preferentially inherited together with a specified intron sequence. When this occurs, the sequences are said to be in linkage disequilibrium. As a result, an allele (or particular form) of a gene may be detected not by analyzing the coding region of the gene but rather by amplifying and analyzing non-coding regions known to be in linkage disequilibrium with the allele. The information can be used to diagnose and treat genetic disorders and diseases correlated with those alleles (for example, cystic fibrosis).

The district court granted a motion to dismiss for failure to state a claim (without conducting a claim construction hearing) and found claims 1–25 and 33–36 of the ’179 patent invalid under 35 U.S.C. § 101. On appeal, the parties stipulated that claim 1 (below) was representative of the claims regarding eligibility under §101.

A method for detection of at least one coding region allele of a multi-allelic genetic locus comprising:

  • amplifying genomic DNA with a primer pair that spans a non-coding region sequence, said primer pair defining a DNA sequence which is in genetic linkage with said genetic locus and contains a sufficient number of non-coding region sequence nucleotides to produce an amplified DNA sequence characteristic of said allele; and
  • analyzing the amplified DNA sequence to detect the allele.

CAFC Logic In determining the subject matter eligibility question, the CAFC employed the Supreme Court’s two-part test described in Alice and Mayo. Step one requires a determination of whether the claims at issue are directed to a patent-ineligible concept. If so, step two requires an analysis of the claims for an “inventive concept,” which has been applied as requiring the claims to provide something inventive, beyond mere “well-understood, routine, conventional activity” (in other words, the “inventive concept” cannot be furnished by the law of nature itself). The purpose of step two is to ensure that the claims, when practiced, add up to significantly more than a patent upon the patent-ineligible concept itself.

In part one of the analysis, the CAFC found the relationships recited in claim 1 to be a law of nature, stating “linkage disequilibrium is indisputably a universal, inherent feature of human DNA.” The court further spoke to the breadth of the claims, stating claim 1 covers “any comparison, for any purpose, of any non-coding region sequence known to be linked with a coding region allele” and the methods were not limited to detecting particular alleles linked to any particular non-coding sequences.

In step two of the analysis, the court found claim 1 contained two implementation steps: 1.) “amplifying genomic DNA with a primer pair;” and 2.) “analyzing the amplified DNA sequence to detect the allele.” The court found both of these concepts to be well-understood, routine and conventional activity, citing portions of the patent specification, prosecution history and general knowledge as of the filing date of the ‘179 patent.

The court found two arguments advanced by GTG to be unpersuasive in step two of the analysis. First, GTG argued that the claims required analysis of man-made amplified DNA, which differs from naturally occurring DNA (for example, in methylation status). The court found the amplified sequence to primarily represent the information content of the genomic DNA and that the minor chemical differences between genomic DNA and amplified DNA were irrelevant, mirroring the USSC logic in Ass’n for Molecular Pathology. Second, GTG argued that claim 1 requires a user to to analyze the amplified non-coding DNA sequence to detect the coding region once the non-coding DNA has been amplified and analyzed. In rejecting this argument, the CAFC found that this step was simply a mental step that could be conducted by the human mind and was tantamount to a claim describing the natural law with the instructions “apply it” (again making analogies to Mayo). The court concluded by stating the “simple mental process step of detect[ing] the allele in claim 1, either alone or in combination with the physical steps described above, does not supply sufficient inventive concept to make the claim patent-eligible under §101.”

The court also dismissed, with little comment, GTG’s argument that claim 1 was patentable based on its usefulness, noting that the claims in Mayo and Ariosa were also useful, were held to be invalid under §101, and that the rejection of claim 1 was not based on lack of utility.

Implications This decision clearly shows that certain judges of the CAFC read the requirements of step two of the Alice/Mayo test as requiring a new physical technique to be disclosed in claims and will dismiss arguments that the methods themselves are unique/have not been used. In this case (like in Ariosa), the method claimed was a new and innovative application of knowledge. In addition, did the court not provide adequate consideration of the “primer pair” limitations as requiring a physical structure that would result in a specific application of the natural law? It should be noted that the claims at issue here did not specify particular primer pairs or specific combinations of exon and intron sequences, although the ‘179 specification contained support for such combinations. One wonders whether a claim reciting a specific exon/intron combination with specific primers would be patentable. While such a claim would still rely on the natural law of linkage disequilibrium, the presence of specific compositions and relationships would clearly limit the application of the natural law in a way that relied on a defined combination. In evaluating such claims, courts should consider the USSC warning in Myriad that overzealous application of the subject matter eligibility exceptions will “eviscerate patent law.”

When drafting patent claims to diagnostic techniques or analytical techniques, claims specifying particular applications and particular combinations of physical elements should be included to allow for focused arguments against rejections under §101 when possible.