In the decisions for parallel IPRs concerning challenges to claims of a single patent, both captioned Laboratory Corporation of America Holdings v. Ravgen, Inc.,1, the Patent Trial & Appeal Board ("the Board") found none of the challenged claims unpatentable, determining that Petitioner LabCorp failed to prove that the claims were obvious over the prior art. Instead, the Board determined that a person having ordinary skill in the art ("POSA") would have been dissuaded from combining the teachings of the cited references.
Petitioner LabCorp filed two IPR petitions challenging Patent Owner Ravgen's U.S. Patent No. 7,332,277 B2 ("the '277 patent"). The '277 patent is directed to non-invasive methods for DNA sampling and detection of genetic disorders in a fetus through the analysis of cell-free fetal DNA ("cffDNA"). A key element of the challenged claims was a limitation requiring the inhibition of cell lysis in a sample to increase the proportion of cffDNA in the sample relative to maternal DNA.3 Petitioner argued that the challenged claims of the '277 patent would have been unpatentable on obviousness grounds over various combinations of the references Chiu, Lo, Bianchi, Granger, and Rao.
The Board held that Petitioner failed to show that the claims of the '277 patent were obvious over the cited prior art. Specifically, the Board noted that Petitioner failed to establish that a POSA would have been motivated to combine the teachings of the prior art and found instead that a POSA would have been dissuaded from combining the teachings of the cited references.
Petitioner alleged in IPR 2021-00902 that the challenged claims would have been obvious over Chiu and Bianchi; Chiu, Bianchi, and Granger; or Chiu and Rao. Id. at *4-5. Chiu relates to the effects of different blood processing protocols on the quantification of cell-free DNA in maternal plasma but does not teach a method of preventing cell lysis in the analysis of cell-free DNA. Id. at *17-20. Petitioner alleged that this deficiency was remedied by the teachings of Bianchi, Granger, and Rao.
Petitioner argued that Bianchi, Granger, and Rao all teach the use of paraformaldehyde ("PFA") to stabilize or fix cells within a sample and therefore prevent cell lysis. Patent Owner argued that Bianchi, Granger, and Rao taught that PFA was used to both permeabilize and fix cells for measurement and analysis within a sample. Importantly, permeabilization of a cell membrane would provide routes for cellular contents (including DNA) to escape into the sample being tested.
The Board agreed with Patent Owner, noting that a POSA would be dissuaded from using an agent like PFA that permeabilizes cells and could therefore increase the amount of maternal DNA within a sample when the goal is to measure cffDNA in the sample. Coming to this conclusion, the Board relied in part on testimony from Petitioner's expert that (1) PFA will likely create holes or gaps in a cell membrane; (2) DNA is one thing that can escape a cell when you permeabilize it; and (3) "'any DNA escaping from cells in Chiu can lower the free fetal fraction in a sample' – contrary to Chiu's goals." Id. at *39-40. Thus, the Board held that a POSA would not have been motivated to modify Chiu's method with the teachings of Bianchi, Granger, and/or Rao. Id. at *41-42.
The Board additionally determined that a POSA "would have been dissuaded from adding [PFA] to Chiu's methods because formaldehyde was known to damage nucleic acids." An admission from Petitioner's expert again supported the record, which indicated that formaldehydes—including PFA—have the potential to damage DNA. Id. at *43. The Board noted that Patent Owner provided several studies showing that "a POSA would have been dissuaded from using formaldehyde or PFA in Chiu's modified method" because of the risk of DNA damage, and that Petitioner provided "no sufficient, persuasive evidence or technical reasoning to explain why a POSA would not have been concerned with potential damage to the cffDNA." Id. at *44. Petitioner also made several additional arguments during the oral hearing suggesting motivations to modify Chiu that were not made in its Petition, and the Board quickly noted that making these arguments for the first time at "[t]he oral hearing is too late." Id. at *46.
Finding that Petitioner failed to show that the challenged claims would have been obvious over the prior art, the Board held that none of the challenged claims in IPR 2021-00902 was unpatentable. Id. at *60.
Petitioner set forth nearly identical arguments in IPR2021-01054, with the addition of Lo as another reference that allegedly would have rendered the challenged claims obvious.4 Petitioner argued that the challenged claims would have been obvious over the combination of Chiu, Lo, and Bianchi, and the combination of Chiu, Lo, and Rao. IPR2021-01054 at *5. Like Chiu, Lo is related to methods for measuring the concentration of fetal DNA in samples and, similarly, does not teach a method of preventing cell lysis in the analysis of cell-free DNA. Id. at *22.
The Board found that Petitioner did not show that a POSA would have been motivated to modify Chiu/Lo with the teachings of Bianchi or Rao. Id. at *38. In a nearly identical analysis to the parallel IPR, the Board noted that the use of PFA in Bianchi and Rao would permeabilize a cell membrane and cause maternal DNA leakage into the sample and would therefore be contrary to the goal of Chiu and Lo. Id. at *39-42. The Board also indicated that "the POSA would have had significant, unresolved concerns with introducing formaldehyde, and its potential to adversely affect cffDNA in the modified method of Chiu/Lo, undermining Petitioner's challenge." Id. at *42.
Again, similar to IPR2021-00902, Petitioner presented additional arguments at the oral hearing that were not found in its Petition, and the Board quickly dismissed these untimely arguments and found all other arguments presented by Petitioner unpersuasive. Id. at *47, 56. Because Petitioner failed to show that a POSA would have been motivated to modify Chiu/Lo, the Board held none of the challenged claims in IPR2021-01054 was unpatentable. Id at *48, 53, 61.
These parallel decisions serve as important reminders for practitioners to know the art—what it teaches, and what it doesn't teach. It is unwise to "cherry-pick" supporting evidence and statements from prior art while failing to consider what the art teaches as a whole or what is known to a POSA. If a narrow teaching is to be taken from a cited reference, practitioners would be wise to ensure that the teaching is consistent with the underlying principles and theories of both the reference it was taken from and the art it is being applied to.
If a proposal for modifying the prior art to attain the claimed invention causes the art to become inoperable or destroys its intended function, the case law supports a conclusion that the requisite motivation to make the modification would not have existed. See, e.g., In re Fritch, 972 F.2d 1260, 1265 n. 12 (Fed. Cir. 1992); In re Ratti, 270 F.2d 810, 813 (CCPA 1959); In re Gordon, 733 F.2d 900, 902 (Fed. Cir. 1984); MPEP § 2143.01(V) and (VI).
Similarly, a prior art reference does not render the claimed invention obvious if the reference "teaches away" from the invention. See In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997) (quoting In re Malagri, 499 F.2d 1297, 1303 (CCPA 1974)). As in the LabCorp IPRs, "[a] reference may be said to teach away when a person of ordinary skill, upon reading the reference, ... would be led in a direction divergent from the path that was taken by the applicant." Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1306 (Fed. Cir. 2015). Teaching away is a fairly strict standard though, as a mere lack of preference is not sufficient. See MPEP § 2143(E); Tec Air, Inc. v. Denso Mfg. Mich. Inc., 192 F.3d 1353, 1360 (Fed. Cir. 1999); Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005); In re Gurley, 27 F.3d 551 (Fed. Cir. 1994); In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004); Galderma Labs. v. Tolmar, Inc., 737 F.3d 731, 738 (Fed. Cir. 2013); Bayer Pharma AG v. Watson Labs., Inc., 874 F.3d 1316, 1327 (Fed. Cir. 2017).
As a patent owner, try to point out how the prior art would have led a POSA in a different direction than the claimed invention or why a POSA would not have reasonably expected success from proceeding on the path resulting in the claimed invention. The state of the art at the time of the effective filing date of the invention may have pointed researchers in a different direction than that followed by the inventor. The Federal Circuit has repeatedly recognized that proceeding contrary to accepted wisdom in the art represents "strong evidence of unobviousness." In re Hedges, 783 F.2d 1038, 1041 (Fed. Cir. 1986); W.L. Gore & Assocs., Inc. v. Garlock, Inc., 721 F.2d 1540, 1552 (Fed. Cir. 1983).
Expert testimony can be a valuable tool to explain the teachings of a cited reference or what is generally known in a field. However, expert testimony is a double-edged sword. Careful preparation of expert witnesses can identify problematic areas of an argument or theory that require more attention and consideration. A wholistic understanding of the art is key to generating consistent and compelling arguments that are supported by persuasive expert testimony.
These decisions also remind practitioners to make all reasonably foreseeable arguments within a petition. Here, Petitioner made multiple arguments at the oral hearing that were not found in the petition, and these arguments were quickly dismissed by the Board as untimely and lacking support. As the Board noted in its analysis, "It is of the 'utmost importance' that a petitioner identify with particularity its theories and supporting evidence in the petition itself." IPR2021-00902 at *46 and IPR2021-01054 at *47. Remember to consider all arguments that can be made while preparing a petition, and make sure arguments being presented at oral hearing are supported in the petition.
1. IPR 2021-00902, Paper 55 (P.T.A.B. Nov. 1, 2022).
2. IPR 2021-01054, Paper 51 (P.T.A.B. Nov. 1, 2022).
3. Independent claim 81 is illustrative of the challenged claims and reads:
- A method for preparing a sample for analysis comprising isolating free fetal nucleic acid from a the [sic] sample, wherein said sample comprises an agent that inhibits lysis of cells, if cells are present, and wherein said agent is selected from the group consisting of membrane stabilizer, cross-linked, and cell lysis inhibitor.
4. Independent claim 55 and several claims that depend (directly or indirectly) from it are challenged:
- A method comprising determining the sequence of a locus of interest on free fetal DNA isolated from a sample obtained from a pregnant female, wherein said sample comprises free fetal DNA and an agent that inhibits lysis of cells, if cells are present, wherein said agent is selected from the group consisting of membrane stabilizer, cross-linker, and cell lysis inhibitor.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.