May 2016
Imp-Exp Executive Magazine
By Ningling Wang; Thomas L. Irving; *Stacy D. Lewis
The case law from the Court of Appeals of the Federal Circuit (CAFC) expressly applies a “lead compound” analysis in pharmaceutical patent litigation. This analysis begins with a determination of whether prior art compounds proposed by the patent challenger (“lead compounds”) would have been compounds that one of ordinary skill in the art would have chosen as starting points for further innovation.
Although one can argue about whether the lead compound analysis has been properly applied at the Federal Circuit, the lead compound analysis helps to guard against impermissible hindsight that may arise when a primary prior art reference is selected by identifying a structurally similar compound to the claimed compound, and then proposing suitable modifications of that compound to arrive at the claimed compound. Structural similarity alone does not explain why a person of ordinary skill in the art (POSITA, representing a hypothetical person presumed to have been aware of all pertinent prior art at the time of the invention) would have selected the most structurally similar compound as a starting point for further development.
The lead compound analysis expressly questions whether the selected primary reference was indeed a proper starting point for the obviousness analysis; i.e., lead compounds that a POSITA would have selected as starting points for further development given the knowledge available in the prior art.
So far, in the post-grant patentability challenge proceedings introduced by the America Invents Act (AIA), and in particular, inter partes reviews (IPRs) and post-grant reviews (PGRs), the Patent Trial and Appeal Board (PTAB), refreshingly, is applying the same lead compound approach and relying on the CAFC case law.
For example, in Apotex Inc. v. Merck Sharp & Dohme Corp., IPR2015-00419, Paper 14, at 11 (P.T.A.B. June 25, 2015), Apotex challenged Merck’s claims to a genus of tachykinin receptor antagonists useful in treating inflammatory diseases, pain or migraine, asthma, and emesis. Apotex relied on prior art disclosing a genus of tachykinin receptor antagonists. The prior art listed 601 specific compounds as within the scope of that genus. A secondary reference purportedly provided the motivation to use phosphoramidate prodrugs to modify the parent compound of fosaprepitant (disclosed as one of the 601 compounds in the primary reference) to arrive at the claimed invention.
The Patent Owner took advantage of the opportunity to file a Patent Owner Preliminary Response, arguing that a POSITA would not have looked to the primary reference to develop tachykinin receptor antagonists. and, even if a POSITA did, it would not have picked the one specific compound from the list of 601. Furthermore, the Patent Owner presented evidence of a lot of prior art discussion at the time of the invention of more promising lead compounds.
The PTAB denied the petition for IPR based on obviousness because it found that the Petitioner had not explained why a person of ordinary skill in the art would have picked that one compound for further development out of a list of 600 specific compounds disclosed in the prior art. Even the preferred substituents disclosed in the prior art included hundreds of possible options. Not only would a POSITA have had to select each of the substituents of the asserted lead compound, it would have had to select all of them at the same time.
In Sawai USA, Inc. v. Nissan Chemical Industries Ltd., IPR2015-01647 (P.T.A.B. Feb. 4, 2016), Sawai challenged Nissan’ claims to mevalonolactone derivatives having a quinoline ring and their use as a pharmaceutical for reducing hyperlipidemia, hyperlipoproteinemia, or atherosclerosis. The PTAB denied the IPR petition because it disagreed with the Petitioner’s lead compound analysis.
Petitioner argued that a secondary reference provided the motivation to a POSITA to modify Petitioner’s lead compound, Picard Example 3, to achieve the claimed compound. The PTAB found that the Petitioner failed to show evidence of any particular functional activity to suggest that the compound should serve as a lead compound. Rather, the data disclosed in the Picard reference related to a compound significantly different from Picard Example 3.
It appeared Petitioner’s selection of Picard Example 3 was based on structural similarity, which, by itself, is not enough to inform the lead compound selection. Furthermore, even assuming that Picard Example 3 was an appropriate starting point, the PTAB held that Petitioner did not explain adequately why one would have chosen the particular modification required.
For the Patent Owner, a denial of an IPR petition is a total win - the challenged claims all survive unchanged because no proceeding is instituted. Currently, the PTAB is instituting IPRs at a rate of about 70%, and, if instituted, the claim cancellation rate is nearly 80%.
Although the institution rate and claim cancellation rate are currently slightly lower in pharmaceutical cases (about 60% institution rate and claim cancellation rate), obtaining a denial is a primary objective of a patent owner faced with an IPR petition. A vehicle by which a Patent Owner can tell the PTAB why the petition should be denied is the Optional Patent Owner Preliminary Response (POPR).
If faced with an obviousness challenge in an IPR petition, a Patent Owner may use its POPR to challenge the Petitioner’s asserted lead compound as a starting point. Challenges may be based on a failure to show that there is some kind of superior performance over other starting points, a lack of a desirable characteristic (or presence of an undesirable characteristic) compared to other potential starting points, a more complicated modification required than the development from other potential starting points, or no explanation of how the particular modification would be selected.
Even the level of unpredictability in the art and the degree of expectation of success associated with some of the starting points available to a POSITA could be relied on by the Patent Owner to present, if such unpredictability or lack a reasonable expectation of success could help persuade the PTAB that the POSITA would not have selected the Petitioner’s asserted lead compound to modify to arrive at the claimed compound. That could be an important basis leading to denial of the Petition against the patent owner.
Endnotes
1 These materials have been prepared solely for educational and informational purposes to contribute to the understanding of U.S. intellectual property law. These materials reflect only the personal views of the authors and are not individualized legal advice. It is understood that each case is fact specific, and that the appropriate solution in any case will vary. Therefore, these materials may or may not be relevant to any particular situation. Thus, the authors and Finnegan, Henderson, Farabow, Garrett & Dunner, LLP (including Finnegan Europe LLP, and Fei Han Foreign Legal Affairs Law Firm) cannot be bound either philosophically or as representatives of their various present and future clients to the comments expressed in these materials. The presentation of these materials does not establish any form of attorney-client relationship with these authors. While every attempt was made to ensure that these materials are accurate, errors or omissions may be contained therein, for which any liability is disclaimed.
2 See generally, SeeTom Irving and Mary Henninger, “From Allergan to BMS: Are We Forgetting the Lessons of History?” BNA Pharmaceutical Law & Industry Report, July 25, 2014
3To illustrate the concept of the lead compound analysis, see, e.g., Takeda Chemical Industries Ltd. v. Alphapharm Pty. Ltd., 492 F.3d 1350 (Fed. Cir. 2007); Daiichi Sankyo Co. Ltd. v. Matrix Laboratories Ltd., 619 F.3d 1346, 1354 (Fed. Cir. 2010), cert. denied, (U.S. Mar 21, 2011); and the two-part inquiry provided in Otsuka Pharmaceutical Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280 (Fed. Cir. 2012)(2-part inquiry: Determine whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts; and then determine whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead compound to make the claimed compound with a reasonable expectation of success.).
*Stacy Lewis is a law clerk at Finnegan.
Copyright © Finnegan, Henderson, Farabow, Garrett & Dunner, LLP. This article is for informational purposes, is not intended to constitute legal advice, and may be considered advertising under applicable state laws. This article is only the opinion of the authors and is not attributable to Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, or the firm's clients.
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