Saturday, March 07, 2015

Some details on Sequenom v. Ariosa, a genetic testing case

US Patent No. 6,258,540 is at issue in the case Sequenom v. Ariosa now pending before the CAFC. Sequenom is the assignee and is defending against invalidity under 35 USC 101.

The patent sets out what the inventors did:


Conventional prenatal screening methods for detecting foetal abnormalities and for sex determination traditionally use foetal samples derived by invasive techniques such as amniocentesis and chorionic villus sampling. These techniques require careful handling and present a degree of risk to the mother and to the pregnancy.

More recently, techniques have been devised for predicting abnormalities in the foetus and possible complications in pregnancy, which use maternal blood or serum samples. Three markers commonly used include alpha-foetoprotein (AFP--of foetal origin), human chorionic gonadotrophin (hCG) and estriol, for screening for Down's Syndrome and neural tube defects. Maternal serum is also currently used for biochemical screening for chromosomal aneuploidies and neural tube defects. The passage of nucleated cells between the mother and foetus is now a well-recognised phenomenon (Lo et al 1989; Lo et al 1996). The use of foetal cells in maternal blood for non-invasive prenatal diagnosis (Simpson and Elias 1993) avoids the risks associated with conventional invasive techniques. WO 91/08304 describes prenatal genetic determination using foetal DNA obtained from foetal cells in the maternal blood. Considerable advances have been made in the enrichment and isolation of foetal cells for analysis (Simpson and Elias 1993; Cheung et al 1996). However, these techniques are time-consuming or require expensive equipment.

Recently, there has been interest in the use of plasma or serum-derived DNA for molecular diagnosis (Mulcahy et al 1996). In particular, it has been demonstrated that tumour DNA can be detected by the polymerase chain reaction (PCR) in the plasma or serum of some patients (Chen et al 1996; Nawroz et al 1996).

It has now been discovered that foetal DNA is detectable in maternal serum or plasma samples. This is a surprising and unexpected finding; maternal plasma is the very material that is routinely discarded by investigators studying non-invasive prenatal diagnosis using foetal cells in maternal blood. The detection rate is much higher using serum or plasma than using nucleated blood cell DNA extracted from a comparable volume of whole blood, suggesting that there is enrichment of foetal DNA in maternal plasma and serum. In fact, the concentration of foetal DNA in maternal plasma expressed as a % of total DNA has been measured as from 0.39% (the lowest concentration measured in early pregnancy), to as high as 11.4% (in late pregnancy), compared to ratios of generally around 0.001% and up to only 0.025% for cellular fractions (Hamada et al 1993). It is important that foetal DNA is found in maternal plasma as well as serum because this indicates that the DNA is not an artefact of the clotting process.

This invention provides a detection method performed on a maternal serum or plasma sample from a pregnant female, which method comprises detecting the presence of a nucleic acid of foetal origin in the sample. The invention thus provides a method for prenatal diagnosis.


The first claim is succinct:

A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises

amplifying a paternally inherited nucleic acid from the serum or plasma sample and

detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.


The listed assignee on the US Patent is Isis Innovation which is a wholly-owned subsidiary of the University of Oxford.
In October 2014, there was an announcement that Sequenom has purchased noninvasive prenatal testing intellectual property from Isis Innovation, for $14.55 million, which includes $3.2 million as the final royalty payment due to Isis under the prior agreement and the waiver of $2.1 million in paid legal fees that Isis owed to Sequenom, equenom previously had exclusive rights to this intellectual property under a licensing agreement with Isis Innovation established in 2005.
[Text from]

Kevin Noonan discusses the case in the post Ariosa v. Sequenom -- Ariosa's Responsive Brief.

The discovery was that -- foetal DNA is detectable in maternal serum or plasma samples --
The invention was a method to utilize the foetal DNA to analyze paternally inherited nucleic acid.


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