Section 101 of the Patent Act defines patentable subject matter. The statute says the following:

“Whoever invents or discovers any new and useful process, machine, manufacture, or composition or matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.” 35 U.S.C. 101

In a recently handed down decision  ”Mayo v. Prometheus Laboratories” the US Supreme Court has again taken center stage and emphasized  its view that “laws of nature” and “basic tools of scientific and technological work” are not covered by the above statute and thus are not subject to protection as a patent.

The patent at issue in Prometheus related to the use of “thiopurine” drugs in the treatment of autoimmune diseases such as Crohn’s disease. When a patient ingests the drug, the body metabolizes it in the bloodstream. Because different people metabolize the drug differently, the same dose of the drug affects different people differently, and it has been difficult for doctors to determine whether a particular dose is too low and thus ineffective or too high risking harmful side effects. The patents to Prometheus (US Patent No: 6,355,623 and US Patent No. 6,680,302) covered findings that concentrations in the patient’s blood of the metabolite beyond a certain level indicated that the dosage is too high. The claim at issue was the following:

“A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and

(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,

wherein the level of 6-thioguanine less than about 230 pmol per 8×108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and

wherein the level of 6-thioguanine greater than about 400 pmol per 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.”

The US Supreme Court held that the patent set forth laws of nature – namely, relationships between concentrations of certain metabolites in the blood and the likelihood that dosage of a thiopruine drug will prove ineffective or cause harm. The relationship according to the court is a consequence of the ways in which thiopruine compounds are metabolized by the body -entirely natural processes. According to the court, the “wherein” clause simply tells a doctor about the relevant natural laws, at most adding a suggestion that he should take those laws into account when treating his patient much like Einstein telling linear accelerator operators about his basic law and then trusting them to use it where relevant. In addition, the other steps were already well known in the art (i.e., administering the drug and determining metabolites in the blood). The court stated that the claim is much like a prior claimed process (Flook) held unpatentable which provided a method for adjusting “alarm limits” in the catalytic conversion of hydrocarbons.

In Flook, certain operating conditions (such as temperature, pressure, and flow rates), which are continuously monitored during the conversion process, signal inefficiency or danger when they exceed certain “alarm limits”. The claimed process amounted to an improved system for updating those alarm limits through the steps of (1) measuring the current level of the variable (e.g., the temperature) using an apparently novel mathematical algorithm to calculate the current alarm limits and (3) adjusting the system to reflect the new alarm-limit values”) The Court pointed out that the basic mathematical equation, like a law of nature, was not patentable, and it characterized the claimed process as doing nothing other than “providing a unpatentable formula for computing an updated alarm limit”. The Supreme Court analigized the Prometheus claims to Flook by stating that the claims at issue present a case for patentability that is no stronger than Flook. “Beyond picking out the relevant audience, namely those who adminsiter doses of thiopurine drugs, the claim simply tells doctors to: (1) measure the current level of the relevant metabolite, (2) use particular (unpatentable) law of nature to calculate the current toxicity/inefficacy limts and (3) reconsider the drug dosage in light of the law.” According to the Court, “these instructions add nothing specific to the laws of nature other than what is well-understood, routine, conventional activity, previously engaged in by those in the field. And since they are steps that must be taken in order to apply the laws in question, the effect is simply to tell doctors to apply the  law somehow when treating their patients”.

A possible criticism of the Court’s opinion is the question “What is not a law of nature?”  Is not everything that occurs in the real world a law of nature? Clearly, knowing a lower limit where a drug is ineffective and thus dosage should be increased and an upper limit where dosage to be increased is something that doctors might want to know and will not discover on their own. Without patents to protect the disccovery of such a relationship, will future inventors have any incentive to discover such relationships?

For purposes of the inventor, the more relevant question is how should process patents be written in the future in order to avoid the patent being held invalid as not covering patentable subject matter?  Unfortunately, the Supreme Court decision does not leave much guidance in this respect.

The Supreme Court does give some hints as to what may be patentable by pointing to cases where such process patents were held to be patentable. For example, the Court point to a prior decision (Dierh) where a process used a known mathematical equation (the Arrhenius equation) to determine when (depending upon the temperature inside a mold, the time the rubber had been in the mold, and the thickness of the rubber) to open a press. That patent claim consisted of the steps of : (1) continuously  monitering the temperature on the inside of the mold (2) feeding the resulting numbers into a computer, which would use the Arrhenius equation to continuously recalculate the mold-opening time , and (3) configuring the computer so that at the appropriate moment it would signal a device to open the press.”

While the Court in Diehr held that the basic mathematical equation, like a law of nature, was not patentable, it found the overall process patent eligible because of the way the additional steps of the process integrated the equation into the process as a whole. Those steps included “installing rubber in a press, closing the mold, constantly determining the temperature of the mold, constantly recalculating the appropriate cure time through the use of the formula and a digital computer, and automatically opening the press at the proper time” Importantly, the court noted importantly that in Dierh, the Court nowhere suggested that all these steps, or at least the combination of those steps, were in context obvious, already in use, or purely conventional unlike the steps in Prometheus. The Court further noted that patentees did not seek to pre-empt the use of the equation, but sought only to foreclose from others the use of that equation in conjunction with all of the other steps in their claimed process. These other steps apparently added to the formula something that in terms of patent law’s objective had significance – they transformed the process into an inventive application of the formula. This last point — tying up a field (i.e., tying up a doctor’s subsequent treatment decision whether that treatment does, or does not, change in light of the inference he has drawn using the correlations in the patent) seemed to be what bothered the Court the most as to the claims. The Court stated that they threaten to inhibit the development of more refined treatment recommendations that combine these correlations with later discovered features of metabolites, human physiology or individual patient characteristics.

In conclusion, steps like “determining” which set forth broad language covering conventional or known processes which may preempt future scientific discovery relating to such processes is probably something to try to avoid when drafting process claims. Other than this, each case must be decided based on its own facts, and the likelihood of mixed ad hoc application by the courts to these facts are likely to increase as a result of the decision by the Supreme Court.

The PTO has issued a guidance memo titled “2012 Interim Procedure for Subject Matter Eligibility Analysis of Process Claims Involving Laws of Nature” which can be found at the uspto.gov website under that name. The memo is for use of patent personnel in determining subject matter eligibility of process claims involving laws of nature under 35 USC 101 in view of Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. -, 132 S.Ct. 1289, 101 USPQ2d 1961 (2012) (Mayo).

Some highlights from the memo are that for process claims which focus on use of a law of nature, a natural phenomenon, or naturally occurring relation or correlation, the claim must amount to significantly more than the natural principle itself by including one or more elements or steps that limit the scope of the claim and do more than generally describe the natural principle with generalized instructions to “apply it.” The additional elements or steps must narrow the scope of the claim such that others are not foreclosed form using the natural principel (a basic tol of scientific and technological work) for future innovation. Elements or steps that are well-understood, purely conventional, and routinely taken by others in order to apply the natural principle, or that only limit the use to a particular technological environment (filed-of-use) will not be sufficiently specific.

Example: Claim 1 in Joe’s application reads “a method of determining the increased likelihood of having or developing rheumatoid arthritis in a patient, comprising the steps of: obtaining a serum sample form a patient; contacting the serum sample with an anti-IgM antibody; and determining that the patient has rheumatoid arthritis or an increased likelihood of developing rheumatoid arthritis based upon the increased binding of the anti-IgM antibody to IgM rheumatoid factor in the serum sample.

Claim 2 read, the method of claim 1, wherein the anti-IgM antibody is antibody XYZ.

Claim 1 would be rejected under the PTO analysis because there is a naturally occurring correlation (natural principle/law of nature) between a patient having rheumatoid arthritis and their level of rheumatoid factor IgM, and increased levels of rheumatoid factor IgM shown by increased binding of an anti-IgM antibody indicate a higher likelihood of a patient being diagnosed with rheumatoid arthritis. The additional steps of obtaining and contacting are well understood steps that are routinely conducted to analyze a serum sample.

However, if the antibody XYZ does not occur in nature and is novel and non-obvious, claim 2 would be patent-eligible because it is a practical application as it does not cover substantially all practical application of the correlation because it is limited to those application that use the antibody XYZ.

Some questions here which arise is what if the correlation above between rheumatoid arthritis and antibody XYZ is not known in the art. Does this make a difference?

In Myriad Genetics, Inc., (decided June 13, 2013), the Supreme Court held that genes and the information that they encode are not patent subject matter under section 101, even when such genes have been isolated from the surrounding genetic material.  The claims at issue were the following:

1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO: 2.

The Court construed this claim to mean to mean the DNA code that tells a cell to produce the string of BRCA1 amino acids listed in SEQ ID NO: 2. 

2. The isolated DNA of claim 1, wherein said DNA has the nucleotide sequence set forth in SEQ ID NO: 1.

The Court construed this claim to mean the isolated DNA of claim 1 which has the nuecleotide sequence of SEQ ID NO: 1 which in theis instance was the sequence of cDNA that codes for the BRCA1 mino acids listed in claim 1. Important, SEQ ID NO:1 lists only the cDNA exons in the BRCA1 gene, rather than a full DNA sequence containing both exons and introns. This was a very important point according to the Court.

5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

The Court construed this claim to mean a subset of data in claim 1. In particular, it claims an isolated DNA having at least 15 nucleotides of the DNA of claim 1. The Court stated that the practical effect of claim 5 is to assert a patent on any series of 15 nucleotides that exists in the typical BRCA1 gene. and that because the BRCA1 gene is thousands of nuceotides long, even BRCA1 genes with substantial mutations are likely to contain at least one segment of 15 nucleotides that correspond to the typical BRCA1 gene.

6. An isolated DNA having at least 15 nucleotides of the DNA of claim 2. 

In formulating its decision, the Court noted that groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the section 101 inquiry. 

Importantly and as noted above with respect to claim 2, the Court states that cDNA does not present the same obstacles to patentability as naturally occurring, isolated DNA segments because a cDNA sequence from mRNA results in an exons only molecule that is not naturally occurring. 

The Court also emphasized that the decision did not effect claims to DNA in which the order of the naturally occurring nucleotides has been altered. 

Method Claims

The Court noted that its decision did not apply to the method claims in the patent.  Accordingly, one needs to look to the earlier Federal Court of August 16, 2013 decision on the method claims. The Federal Court in that earlier decision held two of Myriad claims invalid but one valid. I will now turn to a short analysis of these calims. 

The key words which appear to be prohibited by the Federal Court according to the Myriad decision of the Federal Court are Analyzing or Comparing. This is pointed out by the court from the representative claims (claim 1) below from of the ’999 and ’001 patents.

1. A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set froth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made form mRNA form said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-487 of SEQ ID NO: 1″

1. A method for screening a tumor sample form a human subject for a somatic alteration in a BRCA1 gene in said tumor which comprises comparing a first sequence selected from the group consisting of a BRCA1 gene from said tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made form mRNA from said tumor sample with a second sequence selected from the group consisting of BRCA1 gene form a nontumor sample of said subject, BRCA1 RNA from said nontumor sample and BRCA1 cDNA made form mRNA from said nontumor sample, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said tumor sample form the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said nontumor sample indicates a somatic lateration in the BRCA1 gene in said tumor sample.

In holding the first claim above patent ineligible, the Court noted that the claim recites nothing more than the abstract mental steps necessary to compare 2 different nucleotide sequences: one looks at the first position in a first sequence; determines the nucleotide sequence at that first position; looks at the first position in a 2nd sequence; determines the nucleotide sequence at that first position; determines if the nucleotide at the first position in the first sequence and the first position in the second sequence are the same or different, wherein the latter indicates an alteration; and repeats the process for the next position. The step of comparing 2 DNA sequences is the entire process that is claimed and is invalid under section 101 according to the Supreme Court’s Mayo decision.

The second representative claim 1 above was even worse according to the court in that it did not even contain a step of “determining” the sequence of BRCA genes by, e.g., isolating the genes form a blood sample and sequencing them or any other putatively transformative step. Rather, the comparison between the two sequences can be accomplished by mere inspection alone.

The final representative method claim (claim 20) from the ’282 patent, however, was different.

20. A method for screening potential cancer therapeutics which comprises: growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell in the absence of said compound, determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells, wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.

In holding claim 20 patent eligible, the Court pointed out that the claim does more than simply apply a law of nature. It applies certain steps to transformed cells which are a product of man, not of nature. Additionally, the claim does not cover all cells, all compounds, or all methods of determining the therapeutic effect of a compound. Rather, it is tied to specific host cells transformed with specific genes and grown in the presence or absence of a specific type of therapeutic.