Detecting Natural Phenomena Using Conventional Techniques Found “Directed to” Natural Phenomena at Alice/Mayo Step One
| September 16, 2022
CAREDX, INC. v. NATERA, INC.
Lourie, Bryson, and Hughes. Opinion by Lourie.
Summary
The CAFC held that genetic diagnostic method claims are ineligible for patent, finding that the claims reciting conventional laboratory techniques to perform diagnosis using a naturally occurring correlation are directed to natural phenomena under Alice/Mayo step one, and also lack additional elements to constitute enough inventive concept under Alice/Mayo step two.
Details
CareDx sued Natera and Eurofins in the U.S. District Court for the District of Delaware, asserting that their products infringed one or more patents licensed to CareDx. The district court awarded summary judgment for the defendants, holding that the patents are ineligible for patent under 35 U.S.C. §101. CareDx appealed the district court’s grant of the summary judgment motions of ineligibility.
The patents at issue, U.S. Patents 8,703,652, 9,845,497, and 10,329,607, relate to diagnosis of organ transplant status by detecting a donor’s cell-free DNA (“cfDNA”) circulating in a recipient’s body. The specification, common to all three patents, depicts prior findings that the existence of cfDNA in blood is mostly attributed to dead cells, and had been used for various diagnostic purposes, such as cancer diagnostics and prenatal testing. The specification notes that the cfDNA-based diagnostic scheme is applicable to organ transplant situations, where the recipient’s immune system kills incompatible donor’s cells which in turn release their nucleic acids into the recipient’s stream, such that an increased level of the donor-derived cfDNA may allow for detection of the transplant rejection.
Claim 1 of ‘652 patent recites:
1. A method for detecting transplant rejection, graft dysfunction, or organ failure, the method comprising:
(a) providing a sample comprising cell-free nucleic acids from a subject who has received a transplant from a donor;
(b) obtaining a genotype of donor-specific polymorphisms or a genotype of subject-specific polymorphisms, or obtaining both a genotype of donor-specific polymorphisms and subject-specific polymorphisms, to establish a polymorphism profile for detecting donor cell-free nucleic acids, wherein at least one single nucleotide polymorphism (SNP) is homozygous for the subject if the genotype comprises subject-specific polymorphisms comprising SNPs;
(c) multiplex sequencing of the cell-free nucleic acids in the sample followed by analysis of the sequencing results using the polymorphism profile to detect donor cell-free nucleic acids and subject cell-free nucleic acids; and
(d) diagnosing, predicting, or monitoring a transplant status or outcome of the subject who has received the transplant by determining a quantity of the donor cell-free nucleic acids based on the detection of the donor cell-free nucleic acids and subject cell-free nucleic acids by the multiplexed sequencing, wherein an increase in the quantity of the donor cell-free nucleic acids over time is indicative of transplant rejection, graft dysfunction or organ failure, and wherein sensitivity of the method is greater than 56% compared to sensitivity of current surveillance methods for cardiac allograft vasculopathy (CAV).
The representative claims of the three patents recite somewhat similar procedures, which may be summarized as:
- collecting a bodily sample from the recipient,
- “genotyping” or identifying genetic features that allow for distinction between the donor and recipient,
- “sequencing” or determining the makeup of cfDNA included in the sample, and
- determining, using the genetic features, the amount of cfDNA originating from the donor in the sample.
The specification depicts that the methods are performed using specific techniques that are “standard,” “well-established” and/or reported in prior patents and scientific articles, including sophisticated polymerase chain reaction (“PCR”), such as digital PCR and selective amplification, and next-generation sequencing (“NGS”), all of which are advanced, but already known, techniques in the field.
The district court held that that the asserted claims were patent ineligible as they were “directed to the detection of natural phenomena, specifically, the presence of donor cfDNA in a transplant recipient and the correlation between donor cfDNA and transplant rejection” and also, “recited only conventional techniques.”
On appeal, the CAFC performed the two-step Alice/Mayo analysis to determine patent-eligibility.
- Are the claims “directed to” laws of nature or natural phenomena? – Yes.
CareDx sought to characterize the claimed invention as directed to “improved measurement methods,” in particular, patent-eligible “use of digital PCR, NGS, and selective amplification” allowing for improved accuracy in cfDNA measurement, as opposed to “discovery of a natural correlation between organ rejection and the donor’s cfDNA levels in the recipient’s blood.” CareDx also asserted that the district court improperly considered conventionality of the claimed techniques at step one, essentially merging the two steps into a single-step analysis centered on conventionality.
The CAFC found that the claims satisfy the step one. Two contrasting precedents are notable: Illumina, Inc. v. Ariosa Diagnostics, Inc., 952 F.3d 1367, opinion modified by 967 F.3d 1319, 1327 (Fed. Cir. 2020), and Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). The CAFC noted that this case is different from Illumina, where the claimed improvement was a patent-eligible “method for preparing” a cfDNA fraction that would not occur naturally without manipulation of a starting sample; rather, the asserted claims are akin to those in Ariosa, wherein the claimed diagnostic methods, including the steps of “amplifying” (i.e., making many copies of) a cfDNA sample using PCR and “detecting” a certain type of cfDNA, so as to perform diagnosis using a natural correlation between certain conditions and the level of cfDNA, were found to be “directed to a natural phenomenon.”
The CAFC noted that the conventionally considerations are not limited to step two, and precedents have routinely performed overlapping conventionality inquiry at both stages of Alice/Mayo. The CAFC found that the use of specific laboratory techniques relied on by CareDx only amounts to “conventional use of existing techniques to detect naturally occurring cfDNA.” The CAFC added that the conventionality is supported by the specification’s numerous remarks characterizing the claimed techniques as “any suitable method known in the art” and similar boilerplate language.
- Do the claims recite additional elements, aside from the natural phenomena, which transform the nature of the claim’ into a patent-eligible application? – No.
CareDx’s main argument at step two was that the inventive concept resides in the use of the specific advanced techniques to identify and measure donor-derived cfDNA.
The CAFC disagreed, concluding that the claimed methods lack requisite inventive concept. In reaching the conclusion, the CAFC again pointed to the specification’s admissions of the conventionality of the individual techniques recited in the claims. The CAFC went on to state that “[t]he specification confirms that the claimed combination of steps … was a straightforward, logical, and conventional method for detecting cfDNA previously used in other contexts,” which adds nothing inventive to the detection of natural phenomena.
Takeaway
This case provides a reminder that conventionality of claimed elements may affect both steps of Alice/Mayo test. At step one, the effort to characterize the claim as being “directed to” a patent-eligible subject matter can be thwarted where the claimed elements are undisputedly conventional, in the absence of an unconventional element that is not a judicial exception to eligibility. And at step two, the conventionality of the individual elements and their combination prohibits finding of inventive concept.
When does the absence of evidence turn into evidence of absence? The CAFC vacate their prior decision to now hold that there must be evidence that a skilled artisan would understand silence regarding a limitation to necessarily exclude said limitation.
| September 9, 2022
Novartis Pharmaceuticals v. HEC Pharms Co, Ltd, & Accord Health Care et al.
Summary:
HEC petitioned for rehearing of a CAFC prior decision in this case, (21 F 4th 1362 – Fed. Cir. 2022) in which the CAFC affirmed a final judgement of the Delaware district court determining that claims 1 to 6 of US Patent 9,187,405 are not invalid and that HEC infringes them. The CAFC Panel in the prior case was Judges, Moore (dissent) with Linn and O’Malley. Here, Chief Judge Moore with Circuit Judge Hughes (majority herein after) vacate the CAFC’s prior decision holding that the Novartis claims are invalid for inadequate written description pertaining to a negative limitation.
- Background
Novartis owns the ‘405 patents and markets a drug for treating relapsing remitting multiple sclerosis that purportedly practices the patent. HEC filed an ANDA with the FDA seeking approval to market a generic version of the drug. Novartis sued. The Delaware district count found that the claims were not invalid either as anticipated or for inadequate written description of the no-loading-dose or daily dosage limitations. HEC appeals as to the written description issue of the no-loading dose.
Claim 1 at issue recites in part “a daily dosage of 0.5 mg, absent an immediately preceding loading dose regime.” The appeal at hand being related to the underlined negative limitation. A loading dose is a higher-than-normal daily dose.
The Majority go into detail regarding what is required to satisfy the written description, stating that “[F]or negative claim limitations…. there is adequate written description when., for example, “the specification described a reason to exclude the relevant [element]… A reason to exclude an element could be found in ‘statements in the specification expressly listing the disadvantages of using’ that element and alternatives to it…. Silence is generally not disclosure.” The Majority further noted that the negative limitation may not be recited verbatim in the specification, but there “generally must be something in the specification that conveys to a skilled artisan that the inventor intended the exclusion, such as a discussion of disadvantages or alternatives.” However, the Majority further noted that while “a written descriptions silence about a negative claim limitation is a useful and important clue and may often be dispositive, it is possible that the written description requirement may be satisfied when a skilled artisan would understand the specification as inherently disclaiming the negative limitation.”
The district count had found that the negative limitation was supported because the prophetic trial described therein states “initially” giving a daily dose, thus this would inform the skilled artisan that there was no loading dose. The Majority found this interpretation erroneous arguing that because the specification says “Initially patients receive treatment for 2 to 6 months” it is clear this sentence speaks to the initial length of treatment and not the dosage. The Majority believed that one of the two Novartis experts admitted this, and that the contrary testimony by the second Novartis experts was inconsistent with the plain text of the specification and therefore carried no weight.
Next, the Majority discussed the district courts finding that the specifications disclosure of a daily dosage combined with its silence regarding a loading dose would tell a person of skill that loading doses are excluded. However, the Majority countered that a patent is not presumed complete such that things not mentioned are necessarily excluded. The Majority noted that the applicants added the limitation during prosecution to address a prior art rejection arguing that the limitation was “to specify that the [daily dosage] cannot immediately follow a loading dose regiment” and “to further distinguish their claims.” The Majority argued that if reciting “daily dosage” without mentioning a loading dose necessarily excludes said loading dose, there would have been no reason for the applicants to add the limitation.
The Majority noted that the expert testimony focused on where in the specification the patentee would have mentioned a loading dose if they intended a loading dose to be included, but that is not the issue at hand, rather the question is whether the patentee precluded the use of a loading dose. The Majority concluded that there is no evidence that a skilled artisan would understand silence regarding a loading artisan to necessarily exclude a loading dose.
Thus, the Majority vacated their prior decision and reversed the distinct courts judgement that the claims of the ‘405 patent are not invalid.
- Dissent:
Circuit Judge Linn dissented, her opinion being very reminiscent of her opinion in the prior judgment, for which she penned the Majority. CJ Linn stated that the “majority in its analysis employs the heightened standard of “necessary exclusion” against which to assess the district court’s fact findings in this case and uses that standard to conclude that the district court clearly erred.” CJ Linn argued that the central tenet of the written description jurisprudence is that the disclosure must be read from the perspective of a person of skill in the art. Here, CJ Lin argued that the district conducted an objective inquiry into the four corners of the specification and found sufficient written description, while also crediting the expert testimony. In particular, the testimony that one skilled in the art would understand the loading dose to be excluded, and that loading dose regiments have been used in the prior art for treating MS. CJ Linn concluded this is sufficient to show that claim language that precludes the administration of a loading dose is supported.
Take-away:
- When express support for a negative limitation is absent, look for evidence that a skilled artisan would understand the silence regarding the limitation to necessarily exclude said limitation.
- Be mindful of statements made during prosecution as to why an amendment is being made.
