by Dennis Crouch
I have been following the ongoing case of Natera v. NeoGenomics that is currently on appeal before the Federal Circuit. Docket No. 24-1324. The technology in these cases has amazing potential and I have several friends who have used these techniques to detect early stage cancer.
The particular litigation here centers on Natera’s US Patent No. 11,519,035 issued on December 6, 2022 that covers a method of detecting cancer through analysis of cell-free DNA (cfDNA) obtained from blood samples. The basic idea is that small fragments of DNA that are released into the bloodstream by cells, including cancer cells. High throughput extraction and sequencing technologies can then be used to detect mutations and their potential associated risk factors, including the presence of cancer and the specific type of cancer. cfDNA cancer screening has lots of advantages, most notably, it is almost non-invasive (blood sample) and provides potential early across the entire body. It can be particularly effective for detecting reemergence of cancer for someone in remission because the particular mutation is already known. This is known as a “tumor-informed” test.
Natera’s ‘035 patent is directed to methods for amplifying and sequencing cell-free DNA (cfDNA) to detect cancer. The claimed invention involves three key steps: (1) tagging cfDNA with universal adaptors, (2) amplifying 25-2,000 single nucleotide polymorphism (SNP) loci in a single reaction volume, and (3) performing massively parallel sequencing. Each of these steps were known in the prior art, but the combination of all three appears to be new. NeoGenomics is accused of infringing through its use of its RaDaR, an independently developed cancer-detection test that purportedly employs a similar process for analyzing cfDNA to provide highly sensitive detection of cancerous mutations. NeoGenomics disagrees, arguing the claims require the tagging and targeted amplification to occur in separate PCR reactions with different primer sets, and that its approach combines this process.
The district court case is still pending in the Middle District of North Carolina (23-CV-629), with the present appeal set-up by the district court’s issuance of a preliminary injunction barring NeoGenomics from utilizing its RaDaR test.
The District Court’s Preliminary Injunction Ruling
In its preliminary injunction order, the district court sided with Natera. It found that Natera “made a strong showing that the RaDaR test made and sold by NeoGenomics uses the method claimed in the ‘035 patent and infringes.” The result then is that NeoGenomics is barred from offering or marketing its product to new patients. In its December 2023 order, the district court made an exception for existing patients and clinical studies already in process — those uses can continue.
In an ordinary case, an accused infringer can keep doing what it has been doing throughout a lawsuit, and is only required to change its behavior upon final judgment, and only if the court orders it to do so. Some accused infringers try to take some voluntary steps immediately in order to avoid building up potential damages, but many do not. A patentee who wants to stop ongoing infringement at the start of the case can petition for preliminary injunctive relief, a judicial equitable remedy that can prohibit the accused infringer from making and selling the allegedly infringing product or service before a trial on the merits. The patent act does not particularly identify preliminary injunctions as an available remedy, but does state that courts “may grant injunctions in accordance with the principles of equity to prevent the violation of any right secured by patent, on such terms as the court deems reasonable.” 35 U.S.C. § 283.
Under the “principles of equity”, the Supreme Court has identified a general four-part test for preliminary relief. The test is substantially the same as the eBay test for permanent injunction with one key difference – the requirement of showing a likelihood of success on the merits. This is required since, unlike permanent injunctions, this is preliminary relief and a jury has not yet decided whether the patent is valid and infringed. Thus, to obtain relief a patentee must demonstrate:
- a likelihood of success on the merits,
- irreparable harm in the absence of an injunction,
- the balance of hardships favors the patentee, and
- an injunction is in the public interest.
Abbott Labs. v. Sandoz, Inc., 544 F.3d 1341 (Fed. Cir. 2008). The likelihood of success factor requires the patentee to show “that it will likely prove infringement, and that it will likely withstand challenges, if any, to the validity of the patent.” Titan Tire Corp. v. Case New Holland, Inc., 566 F.3d 1372 (Fed. Cir. 2009). If the accused infringer raises a “substantial question” regarding validity or infringement, a preliminary injunction should not issue. Importantly, the issuance of a preliminary injunction within the district court’s reasonable discretion, even if the patentee makes the required showing. The decision to grant or deny a preliminary injunction is reviewed on appeal for abuse of discretion.
The District Court’s Reasoning:
On validity, the court rejected NeoGenomics’ obviousness challenge, finding its prior art arguments “appear to show hindsight bias more than they support a substantial question of obviousness.” The court emphasized the “challenges associated with cfDNA” that made it “unlikely a person skilled in the art would have been motivated” to apply the prior art techniques with “anticipated success.” Turning to irreparable harm, the court stressed that Natera and NeoGenomics are “direct competitors” in the concentrated tumor-informed minimal residual disease (MRD) testing market. Without an injunction, Natera would likely lose “customers, profits, business relationships, and clinical opportunities,” amounting to irreparable harm.
Key Issues on Appeal
On appeal, the Federal Circuit has been asked to scrutinize the district court’s application of the preliminary injunction factors. The central issues include:
1. Claim Construction: Did the court err by not explicitly construing the tagging and amplification limitations? NeoGenomics contends the claims require separate PCR reactions for each step, while Natera maintains they only require the steps to occur sequentially.
2. Obviousness: Did the court demand too much for obviousness and improperly focus on unclaimed features? NeoGenomics argues Natera’s admissions in other cases show that using the claimed DNA processing steps on cfDNA was routine. Although Natera’s product is successful, those results are not claimed — only the process in broad terms. NeoGenomic argues that the lower court erred by focusing on these unclaimed results.
3. Irreparable Harm: Did Natera show a sufficient causal nexus between the alleged harm and infringement? NeoGenomics attacks the irreparable harm finding as based on unclaimed tumor-informed testing, not the specific claim limitations. This argument seems odd – it is essentially that the patent claims are so broad that there can be no irreparable harm associated with Neo’s narrow use.
4. Public Interest: Did the court properly balance the interests of cancer patients and researchers? NeoGenomics contends RaDaR’s unique attributes make it essential for certain clinical uses in a way Natera’s competing product (Signatera) cannot match.
In the case, the Federal Circuit appears to be moving quite quickly and I expect a quick decision from the panel – especially if the court overturns the injunction.
The panel here includes Chief Judge Moore and Judges Taranto and Chen. Arguing counsel: Deanne Maynard for NeoGenomics Laboratories, Inc. and Jeffrey A. Lamken for Natera, Inc.
The district court case is ongoing with trial date set for March 2025.
Another one for my scheme:
Is it a method? Yes
Is the useful result of the method an item of information? Yes
Does the utility of the information arise in a human mind? Yes, Ineligible
In actually existing patent law, it seems like this turns on distinguishing Sequenom…but also raises the question: will more net lives be saved if this patent stands, or falls?
So … PCR is ineligible according to this ridiculous methodology?
What if the claimed method is a diagnostic reaction that is carried out using a novel and non-obvious recombinant enzyme?
Is PCR a method? Yes
Is the useful result of the method some item of information? No.
The result of the method is an amplification of physical structure resulting in a scaled physical representation of the original
End of inquiry
****************************************************
Is a a novel and non-obvious recombinant enzyme some item of information? No, it’s a novel and non-obvious physical structure.
End of inquiry
Not so fast, Martin.
“Is the useful result of the [PCR] method some item of information? No.”
The correct answer is “it depends on the intent of the person running the reaction.” This seems like a problem for your method eligibility test.
As for the second question, you completely ducked. The question is not about the eligibility of a composition claim to the non-obvious recombinant enzyme. It’s about the eligibility of a diagnostic method claim that utilizes (and recites) that enzyme. Of course, you could argue that the “useful result” of that method is the cleavage or joining of some chemical bond but you wouldn’t dare try that, would you?
Intent?
His hypo is not about intent, but about your very own ‘desired’ single objective physical structure.
You two should be high-fiving, eh?
PCR as a method should be eligible in a reasonable eligibility scheme, we agree on that?
Even if PCR were not a novel physical process, which it is, if you wish to characterize the result of the method as some item of information (it’s not mere information, it’s a scaled amplified composition) then you move to the next step in my test:
Is it a method? Yes
Is the useful result of the method an item of information? Yes
Does the utility of the information arise in a human mind?
For PCR alone, the answer is no. No human being is going to directly make use of the sizes & charges generated by the process. The utility arises in the amplification itself.
If some of the uses of the amplification involve diagnostic correlations, they should not be eligible, because that information is directly consumed by human minds.
The question is not about the eligibility of a composition claim to the non-obvious recombinant enzyme
Isnt it? You said it was “a diagnostic reaction that is carried out using a novel and non-obvious recombinant enzyme?”
If the infringing act is running the process with the novel and nob-obvious enzyme, it seems like that should be an eligible method.
If there are diagnostic correlations revealed by the method that are used by humans to make treatment decisions, as with PCR, those methods should be ineligible.
If there are further laboratory processes or some non human use of the reaction, those methods should be eligible.
As a policy and practical matter, of course the intent of the user of some item of information is critical to the eligibility of the information, if we are going to allow patents on new and useful information at all, which we probably shouldn’t.
Unfortunately, too many other reasonable minds think we should.
“ If the infringing act is running the process with the novel and nob-obvious enzyme, it seems like that should be an eligible method.”
Ah, yes, you made it first base and you understand what I clearly wrote. Congrats!
“ If there are diagnostic correlations revealed by the method that are used by humans to make treatment decisions, ”
It doesn’t matter what correlations or information is revealed by the method that we agree is eligible. That changes nothing. The claim at issue remains eligible. I’m not interested in discussing ineligible diagnostic methods where information is obtained using NON-NOVEL or OBVIOUS methods. That’s a separate discussion and a boring one at this point.
Regarding your strange contortions with respect to PCR, I’ll just state the plain facts again: the eligibility of PCR did not hinge on any particular use for the amplified molecules. PCR is both a method for synthesizing DNA and a method for detecting DNA. If the detected DNA has some “meaning”, that didn’t make the claim to PCR ineligible. After PCR was disclosed, of course, claims to methods of using it to detect “this cancer” or “that cancer” should certainly be ineligible for the same reason that using a prior art magnifying glass to magnify “this insect” or “that insect” are ineligible, regardless of whether the insect was newly discovered in the Amazon.
Please Pardon Potential re(P)eat…
Your comment is awaiting moderation.
April 4, 2024 at 12:06 pm
You are conflating eligibility and patentability.
Again.
Comment in filter.
Wasn’t the Sequenom case about cell-free DNA detection also? Why wasn’t 101 raised here?
Don’t get me wrong – Sequenom was wrongly decided, and I’m glad to see that the present case has stayed away from the 101 b.s.
Sequenom’s claims weren’t tanked merely because the claims were “about cell-free DNA detection.”
OT but bwahahahahahaha ….
“ Just over half of Amazon Fresh stores are equipped with Just Walk Out. The technology allows customers to skip checkout altogether by scanning a QR code when they enter the store. Though it seemed completely automated, Just Walk Out relied on more than 1,000 people in India watching and labeling videos to ensure accurate checkouts. The cashiers were simply moved off-site, and they watched you as you shopped.”
(these same people will help you drive your car “automatically”, too)
How old was that source?
Try this one: link to apnews.com
The invention is the discovery that that DNA from cancer cells is found in cell free DNA circulating in the blood, and that the cancer cell DNA can be distinguished based upon SNPs. PCR is used to amplify that DNA.
from claim 1 – “wherein the plurality of
SNP loci comprises 25-2,000 loci associated with cancer. “
“ The invention is the discovery that that DNA from cancer cells is found in cell free DNA circulating in the blood”
This is false and you s u c k.
Didn’t check out the claims? Just click on the link to the opening brief.
“1. A method for amplifying and sequencing DNA, comprising:
tagging isolated cell free DNA with one or more universal tail adaptors to generate tagged products, wherein the isolated cell-free DNA is isolated from a blood sample collected from a subject who is not a pregnant women;
amplifying the tagged products one or more times to generate final amplification products, wherein one of the amplification steps comprises targeted amplification of a plurality of single nucleotide polymorphism (SNP) loci in a single reaction volume, wherein one of the amplifying steps introduces a barcode and one or more sequencing tags; and
sequencing the plurality of SNP loci on the cell free DNA by conducting massively parallel sequencing on the final amplification products, wherein the plurality of SNP loci comprises 25-2,000 loci associated with cancer.
What are the last 4 words in the claim? “loci associated with cancer”
What is “false” (and plainly so) is the idea that the named inventors on this patent discovered and first disclosed in this patent that “DNA from cancer cells is found in blood serum/plasma”. That discovery was made at LEAST 35 years ago.
Gist much?
DC: “The technology in these cases has amazing potential”
To be clear, the basic technology here is the polymerase chain reaction (PCR) and its potential was understood with crystal clarity shortly after its invention circa 1983, which is about 40 years ago now. That potential, for those unfamiliar with the technology, was the potential to identify (and amplify) vanishingly small amounts of particular DNA sequences (polymers of nucleotides) lurking in a mixture of DNA sequences and other molecules, including complex mixtures such as blood, other tissues, saliva, tears, soil, semen, feces and rain puddles. Everybody who knew anything about biochemistry recognized the potential. The devil was in the details, as always, but the broad strokes of those details were also evident: purification, concentration, and signal amplification.
Any DNA detection claims relying on PCR that recite in combination only the broad strokes of existing technologies in these categories but fail to provide critical and novel details should be viewed with a jaundiced eye.
And in an analogy, protons, neutrons and electrons can make up every substance in the universe.
Here, I have a big box of them. This, anything being attempted to be patented is only grifting off of my big box.
The panel here includes Chief Judge Moore and Judges Taranto and Chen. Arguing counsel: Deanne Maynard for NeoGenomics Laboratories, Inc. and Jeffrey A. Lamken for Natera, Inc.
Given that panel, this patent will fall.
Or in legal terms, the “likelihood of success on the merits” factor ALWAYS favors the defendant nowadays 😉
Who is on the CAFC panel?