A Method of Diagnostic Sample Preparation Is Held Valid Under Mayo/Myriad, but the Diagnostic Test Was Held InvalidNearly five years ago the U.S. Court of Appeals for the Federal Circuit (CAFC) decided the controversial case of Ariosa v. Sequenom. In Sequenom the invention was a radically new method of fetal genetic testing by amplifying free paternal DNA from the mother’s blood. This test has today largely replaced the previous method of amniocentesis, which was an invasive test with a very high risk of complications. There was no evidence that anyone had ever conceived of testing a pregnant woman’s blood for fetal DNA (paternal or otherwise) for any purpose. The claims were only to selectively amplifying paternal DNA; no abstract diagnostic step was claimed. The CAFC considered the act of amplifying paternal DNA to be a mere recognition of a natural phenomenon: that fetal DNA is present in the mother’s bloodstream. The CAFC decided that remaining claim limitations, such as the use of the polymerase chain reaction (PCR), were too well known and conventional to add any inventive concept to the recognition of the natural phenomenon. Although the CAFC recognized that the invention in question was quite brilliant and highly useful, replacing the risky procedure of amniocentesis with a simple blood test, they famously repeated the Supreme Court’s commandment that “groundbreaking, innovative, or even brilliant” inventions do not necessarily involve an “inventive concept” under the law.

In an unusual turn, the CAFC has held two closely related patents to be valid in a dispute between the same parties. The patent in dispute in the more recent case (Illumina, Inc. v. Ariosa Diagnostics, Inc.) did not claim the fetal DNA test itself, but a method of preparing the sample for testing for fetal DNA. The inventors developed a method to isolate acellular DNA of maternal origin from acellular DNA of fetal origin in the blood of pregnant woman; the isolated fetal DNA can then be genetically analyzed. It was discovered that the maternal DNA is mostly above 500 bp in size, whereas the fetal DNA is mostly below 500 bp in size. Accordingly, the inventors tested and patented a method of separating acellular DNA from blood based on size.  Claim 1 of U.S. Pat. 9,580,751 was one claim analyzed in the decision, which reads:

  1. A method for preparing a deoxyribonucleic acid (DNA) fraction from a pregnant human female useful for analyzing a genetic locus involved in a fetal chromosomal aberration, comprising: (a) extracting DNA from a substantially cell-free sample of blood plasma or blood serum of a pregnant human female to obtain extracellular circulatory fetal and maternal DNA fragments; (b) producing a fraction of the DNA extracted in (a) by: (i) size discrimination of extracellular circulatory DNA fragments, and (ii) selectively removing the DNA fragments greater than approximately 500 base pairs, wherein the DNA fraction after (b) comprises a plurality of genetic loci of the extracellular circulatory fetal and maternal DNA; and (c) analyzing a genetic locus in the fraction of DNA produced in (b).

The court categorically stated that methods of medical diagnosis cannot be patented, but methods of medical treatment can be patented; however, the court also said that the claims in this case were neither methods of medical treatment nor methods of medical diagnosis.

The court applied “step 1” of the Alice/Mayo test for patent eligibility to determine whether the claims were “directed to” one of the judge-made exceptions to patent eligibility, those being “natural phenomena,” “laws of nature,” and “abstract ideas.”  The court found that the invention utilized a “law of nature,” specifically that maternal DNA in the blood tends to be larger than fetal DNA in the blood. However, in the court’s opinion “… the claims are not directed to that natural phenomenon but rather to a patent-eligible method that utilizes it.”

The court justified upholding the validity of this patent while invalidating the patent for the underlying test based on its understanding that the instant patent claimed method “change[s] the composition of the mixture, resulting in a DNA fraction that is different from the naturally-occurring fraction in the mother’s blood. Thus, the process achieves more than simply observing that fetal DNA is shorter than maternal DNA or detecting the presence of that phenomenon.” The court contrasted the current claims with those that were previously invalidated by saying that the previously invalidated claims were directed only to “detecting a natural phenomenon.”

This opinion creates the possibility, that although detecting a biomarker cannot be patented, a process of isolating an analyte can be patented. This provides a potentially advantageous approach to patenting new methods of diagnosis based on newly recognized biomarkers – patent the method of isolating the biomarker or otherwise preparing the sample for analysis. The viability of that approach of course depends on whether the method of isolating the biomarker is otherwise patentable, i.e., it must be novel and non-obvious. This decision further refines the CAFC’s position on the patentability of method of medical diagnosis, methods of medical treatment, and related inventions.