By Kevin E. Noonan --
The U.S. Patent and Trademark Office has a history of attempting to challenge judicial decisions that the Office, usually for its own policy reasons, takes issue with.[1] Recently, the Office decided to challenge the rationale behind the Supreme Court's decision in KSR v. Teleflex for certain technologies, specifically by advocating that claims to dosage regimens for pharmaceuticals should be almost per se obvious, particularly for such claims for which the pharmaceutical was itself patent protected; in the Office's defense, the motivation appears to be eliminating so-called "evergreening" patents.[2] The relevant portion of the KSR decision involved in this effort provides a standard that requires there to be a reasonable expectation of success when prior art is combined:
When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.
The technology at issue (in U.S. Patent Application Publication No. US 2015/0132323 A1) is directed to methods for treating ovarian cancer patients using an antibody-drug conjugate ("ADC") called mirvetuximab soravtansine. The methods specified in the rejected claims specify that the administered dose be calculated from the adjusted ideal body weight (or "AIBW"), which will vary from patient to patient and will also likely vary for the same patient during the course of the treatment. This is a different standard from the total body weight (or "TBW") used in the prior art. The claimed methods solved a previously unknown problem, that mirvetuximab soravtansine dosed using TBW led to an unacceptable level of ocular toxicity, and the inventors' unexpected solution to this problem, that such ocular toxicity was significantly alleviated if the same drug was dosed using AIBW.
This is the second time Immunogen has come before the Federal Circuit to appeal rejections for indefiniteness and obviousness from the Patent Office.[3] In the first case, Immunogen challenged the rejections by filing suit under 35 U.S.C. § 145 and the district court held for the Office on summary judgment. The Federal Circuit (before a panel of Judges Newman, Stoll, and Clevenger) vacated and remanded. With respect to obviousness, the Court's judgment was based on factual errors appreciated by the panel, finding that there were genuine issues of material fact in dispute.
Here, the Office once again prevailed at the district court on Immunogen's § 145 action and once again Immunogen has appealed to the Federal Circuit. What is new in this appeal is one of the positions taken by the Office. In its briefing, the Office has taken the position that claims to methods for administering drugs (particularly ones subject to independent patent protection) that rely, as do Immunogen's, on dosing regimens are (almost per se) obvious. Importantly, this position includes an attack on Immunogen's argument that the claims were non-obvious because the unpredictability of these claims would preclude the skilled worker from having the requisite reasonable expectation of success. The Office decries this argument, asserting that "ImmunoGen should not be able to use 'unpredictability' as talisman for getting a patent. Otherwise, drug companies may be able to get patent protection on any follow-on pharmaceutical development no matter how obvious to try -- because the result of pharmaceutical experiments are nearly always somewhat unpredictable."
Despite the Office's protestations, unpredictability has been a hallmark of biotechnological inventions and has been recognized almost from the dawn of biotechnology patenting. The doctrinal approach to determining the distinction between what is obvious to try and what is obvious under the statute was set forth by Judge Rich in In re O'Farrell and reiterated (with broadening to all technologies) in KSR v. Teleflex (which was concerned with obviousness of an electromechanical device). Immunogen raised several fact-based distinctions with the Office's position, including that just because AIBW was known in the art (in contexts other than administering ADCs) does not render its use obvious in these claims because, inter alia, ADC administration is known to be unpredictable. The Office argues that AIBW has been used to identify dosages in pharmaceutical compositions ranging in size from small molecule drugs and to CD34+ cells, but these arguments disregard the qualitative differences between these reagents and ADCs due to the unique characteristics of the latter pharmaceuticals. The Office's arguments generalize dose optimization methods without regard to the particular properties and characteristics of ADCs which make their used unpredictable as known in the art (exemplified by the undisputedly high level of skill of the person having ordinary skill in this art). This is not to mention that AIBW had never been used for determining ADC dosages until successfully used by Immunogen for mirvetuximab soravtansine.
As sanctioned by the Supreme Court, the standard for determining obviousness is whether the combination leads to success anticipated by a person of ordinary skill in the art and thus the predictability of the prior art combination is a necessary consideration, whether the art is inherently predictable or not. The Office's position also ignores evidence that doses determined using the AIBW method resulted in reduced or eliminated ocular toxicity, a deleterious side-effect not appreciated in the prior art (as determined by the district court). These facts implicate another part of the Supreme Court's KSR rubric, which requires that obviousness can properly be found where "there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions," neither of which was the case here. This distinction further supports the non-obviousness of Immunogen's claims.
Late in the appellate proceedings, the Office asserted the recent Federal Circuit decision in Janssen Pharmaceuticals v. Teva Pharmaceuticals. In that case, the Federal Circuit (in a panel comprised of Judges Dyk, Prost, and Hughes) vacated and remanded the district court's determination in ANDA litigation regarding an antipsychotic medication that the asserted claims were non-obvious. In its opinion, the panel found fault with the district court's determination of non-obviousness based on its consideration of claims teaching generally what doses should be used (based on confidential clinical trial evidence of patient populations not available to the skilled worker) despite reciting that the dose was determined for "a" psychiatric patient. The error appreciated by the Court was that in considering whether there was a reasonable expectation of success in the district court's obviousness determination the court evaluated a "generalized multi-dose regimen" of the population contrary to the limitation to "a" psychiatric patient recited in the claims. The Office has represented to the Federal Circuit that this decision means that if there is no difference in dosing for some patients between the AIBW- and TBW-based dosages then the claims would have been obvious (as the Office has argued). However, the Office does not provide any evidence showing that such hypothetical ovarian cancer patient even exists. More importantly, this argument ignores the basis of the Federal Circuit's decision in Janssen that the claims by their terms were limited to dosage considerations to "a" psychiatric patient and thus the district court erred in applying the KSR framework to predictability in a population. Here, immunogen's claims require calculation of AIBW for each patient before dosing. Therefore, even if a method using TBW resulted in the same dose for a particular patient as calculated using AIBW, that method is different from and not covered by the "claimed" method because it involves a different calculation.
It should also be appreciated that the basis for the Office's position appears to be related to its efforts to assess the extent to which secondary patents contribute to (or are responsible for) excessive drug prices (the relationship having been debunked by several knowledgeable commentators). The Office has asserted that it is "problem[atic]" that "this Court routinely cites the unpredictability of the pharmaceutical arts as a basis for upholding follow-on pharmaceutical patents" and illustrates the problematic nature of this approach by citing CAFC's prior decision in this case and a string of precedential decisions.
But these policy concerns cannot justify the Office urging the Federal Circuit to ignore established precedent regarding how obviousness is to be determined (in a technology-agnostic way), directly contrary to Supreme Court precedent. And in view of the Supreme Court's decision in Loper Bright v. Raimondo, it is improper for the Office, as an administrative agency, to do so no matter its motivations.
[1] For example, the Federal Circuit ruled not once (In re Bell) but twice (In re Deuel) that the Office misapplied the law on obviousness by using the purported obviousness of a method of isolating a gene as evidence that the isolate gene itself was obvious. Another example involved the Office's rejection of biotechnology inventions based on the enablement requirement; when a new Commissioner precluded such rejections the Examining Corps imposed the same rejections on the utility prong of Section 112, first paragraph. This attempt at extrajudicial policymaking only ceased with the Federal Circuit decision in In re Brana.
[2] This latest tactic was also in response to the Biden Administration's efforts to identify and correct any influence patent law has had on excess drug prices (that connection having only tenuous support; see, e.g., Mossoff, 2022, Policy Memo: Unreliable Data Have Infected the Policy Debates Over Drug Patents, Hudson Institute.
[3] Only the obviousness rejection is discussed here.