The USPTO Patent Trial and Appeal Board found that treatment of a subject for pre-eclmpsia based on the elvel of soluble endoglin and sFlt-1 together was a specific application of natural principles that is not conventional. Appeal 2015-00426 US application 12/226,658.

The claim at issue was the following:

A method of diagnosing a subject as having, or having a predisposition to, preterm pre-eclampsia, said method comprising measuring the level of a soluble endoglin polypeptide and an sFlt-1 polypeptide from said subject and calculating the relationship between said levels of soluble endoglin and sFlt-1 using a [soluble endoglin x sFlt-1] metric, wherein an increase in the metric value in the subject sample realtive to the metric value in a normal reference sample, is a diagnostic indicator of, or a propensity to evelop, pre-term pre-eclampsia in said subject, and based on said diagnosis treating said subject for said pre-eclampsia.

The examiner rejected the claim as being drawn to a mathematical relationship between polypeptide levels in a pateint sample and the presence of a particular disorder which is a law of nature. 

The Board agreed. Important to the decision was evidence that the specification itself pointed to the fact that the claimed measurement steps were well-understood and/or convention and routin. Regarding the “treating” step, the examiner found that not only is the step specified at a high level of generality as it encompasses and and all possible treatments for pre-eclampsia, but that treating “after amking a diagnosis …is obvious and routin int he medical arts.” In light of this, the examiner found that “no matter how important, unexpected or useful” the discvoery that “increased levels of sFlt-1 and soluble endoglin are correlated with increased risks for preeclampsia and other pregnancy related hypertensive disorders” of the determiantion of “the mathematical equation by which they can be combined to acheive a diagnosis of increased accuracy as compared to the priro art,” the additional measurement and treating steps beyond the mathematical relationship recited in the claims do not transform the law of nature recited by the claim into a patent eligible application of such a law. The Board also noted that the the calim could be distinguished from Example F of the “2014 Guidance for determining Subject Matter Eligibility of Claims Reciting or Involving Laws of Nature, Natural Phenomena, & Natural Products” because there the claim made use of a novel product. In contrast, here there was a prior art publication that taught methods for diagnosing pregnancy related hypertensive disorder or a predisposition to a pregnancy realted hypertensive disorder, such as preeclampsia, by measuring soluble endoglin (sEng) in combination with other markers including soluble Flt-1, calculating a diagnostic index which adds sFlt-1 and sEng concentraiton values, and methods of treating women so daignosed.

Some take home points:

1. The Board and examiner noted that the claim did not specify any particular type of treatment, such as use drug A rather than drug B. There is nothing in the general statement to treat after the diagnosis is made that could be deemed an unconventional step. The claim thus preempts all practial uses of the natural law/phenomenon/correlation”. This suggests that particular types of treatment steps might be enough to make a claim a practical application of the natural principle.