In an attempt to expand a patent’s disclosure and provide Section 112 support for features not expressly disclosed in the patent specification (such as reagents, assays, techniques, etc.), patent applications are often written with boilerplate text to indicate that other “conventional,” “well-known,” or “routine” features may be used. However, an acknowledgment that features of a claimed invention are conventional, well known, or routine can have a detrimental effect on patentability. Take note of the Federal Circuit’s recent decision CareDx, Inc. vs. Natera, Inc., in which the court found, for example, that methods for detecting organ transplant rejection were directed at “a law of nature along with conventional steps for detecting or quantifying the manifestation of that law.” (CareDx, Inc. vs. Natera, Inc.No. 2022-1027, 2022 WL 2793597, at *8 (Federal Circ. July 18, 2022).)
The disputed patents in CareDx aim to “provide non-invasive methods for monitoring organ transplant patients for rejection that are sensitive, rapid, and inexpensive.” (‘652 patent at Col. 1, lines 23-25.) The claimed methods involve the analysis of differences (ie, polymorphisms) in cell-free nucleic acids between the organ donor and the organ recipient. According to the patents, “The relative amount of donor-specific sequences in circulation [cell-free DNA or RNA] should provide a predictive measure of impending organ failure in transplant patients for many types of solid organ transplants including, but not limited to, heart, lung, liver, and kidney.” (ID. at col. 7, lines 41-46.) Claim 1 of the ‘652 patent, for example, recites:
1. A method for detecting transplant rejection, transplant 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 create a polymorphism profile for detecting donor cell-free nucleic acids, where at least one single nucleotide polymorphism (SNP) is homozygous for the subject, when the genotype includes subject-specific polymorphisms that include 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 cell-free donor nucleic acids and cell-free subject nucleic acids; and
(d) diagnosing, predicting or monitoring a transplantation status or outcome of the subject who received the transplant by determining an amount of the donor cell-free nucleic acids based on the detection of the donor cell-free nucleic acids and the subject cell-free nucleic acids by the Multiplex sequencing, where an increase in the amount of cell-free donor nucleic acids over time is indicative of transplant rejection, transplant dysfunction, or organ failure, and where the sensitivity of the method is greater than 56% compared to the sensitivity of current cardiac allograft vasculopathy (CAV ).
CareDx, the exclusive licensee of the ‘652, ‘497 and ‘607 patents, sued Natera and Eurofins Viracor, Inc., (Eurofins) for patent infringement. (CareDx, Inc.No. 2022-1027, 2022 WL 2793597, at *3.) Natera and Eurofins filed motions for summary judgment of inadmissibility under Section 101. The district court granted Natera’s and Eurofins’ motions, noting that “the claims made were directed to evidence of natural phenomena, particularly the presence of donor cfDNA in a transplant recipient and the correlation between donor cfDNA and transplant rejection” (CareDx, Inc.nos. 2022-1027, at *4), and that “based on the numerous admissions of the description, the claims cited only conventional techniques.” (ID.)
On appeal, CareDx argued that the claimed methods were not aimed at “discovering a natural correlation between organ rejection and the donor’s cfDNA levels in the recipient’s blood” (I would. at *5), but rather to improved measurement methods that are superior to the inadequate measurement techniques of the prior art. (ID.) CareDx claimed that “the use of digital PCR and next-generation sequencing to identify and measure donor-specific SNPs was an inventive breakthrough and that the patents claim this specific and useful application.” (ID.)
However, the Federal Circuit disagreed, upholding the district court’s finding of inadmissibility of the subject matter, noting that the patents “address a natural law, along with conventional steps for detecting or quantifying the manifestation of that law.” (ID. at *8.) According to the Federal Circuit, the methods of the ‘652, ‘497 and ‘607 patents each have the following four steps for detecting cell-free donor nucleic acids from a biological sample of a transplant recipient:
- “receiving” or “making available” a “sample” containing cfDNA from Recipient;
- “Genotyping” of the transplant donor and/or recipient to develop “polymorphism” or “SNP” “profiles”;
- “Sequencing” the cfDNA from the sample using “multiplex” or “high-throughput” sequencing or performing “digital PCR”; and
- “Determining” or “quantifying” the amount of donor cfDNA.
(ID. at 3.)
Under step one of the Alice/Mayo Upon investigation, the Federal Circuit determined that the claimed methods do not relate to a manufacturing process or a new measurement technique, but to natural phenomena. (ID. at *5-7.) According to the court, “The claims boil down to taking a body sample, analyzing the cfDNA using conventional techniques, including PCR, identifying naturally occurring DNA from the donor organ, and then increasing the natural correlation between cfDNA levels and graft health to identify possible rejection, none of which was inventive.” (ID. at *6.) The Federal Circuit was unconvinced by CareDx’s arguments that the claims were directed at improved laboratory techniques because the claims “simply recite the conventional use of existing techniques for detecting naturally occurring cfDNA.” (ID. at *6.) The court noted that “the written description is replete with characterizations of the claimed techniques in terms attesting to their conventionality” (I would. at *5), like the following passage from the specification:
The practice of the present invention utilizes conventional techniques in immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics and recombinant DNA well known to those skilled in the art unless otherwise indicated.
Regarding step two of the Alice/Mayo After an investigation, the Federal Circuit agreed with the district court that the claims “add nothing new because they merely enumerate standard known techniques in a logical combination for detecting natural phenomena.” (ID. at *7.) In its conclusion, the Federal Circuit again focused on the admissions in the patents that the processes use conventional techniques and commercially available technology:
The specification acknowledges that each step in the purported invention requires only conventional techniques and commercially available technology: (1) Collect patient sample using “any technique known in the art,” ‘652 patent at column. 10l. 11; (2) Donor and recipient genotyping for SNP profiling using “any appropriate method known in the art” I would. at col. 20 sheets 31-33; (3) sequencing of the cfDNA using “known” techniques and commercially available tools, I would. at col. 15 sheets 6–8, col. 15 ll. 22-67; and (4) quantification of donor cfDNA using methods “known in the art”, I would. Col. 18 l. 55–column. 19 l. 2.
(ID.) According to the court “
Patent applicants are cautioned against using language that characterizes any part of the invention as conventional, well known, or routine. As evidenced by the CareDx Such wording can be detrimental to patentability, especially when it comes to the suitability of subject-matter. The Federal Circuit has clarified that “the application of standard techniques in a standardized manner to the observation of natural phenomena does not constitute an inventive concept.” (ID.)