2. The Assailability of Amarin Corp.’s Patent Portfolio
2.1 Obviousness and Prior Art
Title 35 (pre-AIA) of the U.S. Code lists the following as conditions for patentability, giving at the same time a working definition of “prior art” relevant to all patent applications filed before March 16, 2013 (or pre-Sept. 16, 2012 for § 112):
In patent law, “prior art” constitutes all relevant reference materials that can show the claimed invention is not novel or is obvious due to it being publicly knowable or in use more than one year prior to the submitted patent application in which the claims reside. This includes, but is not limited to, published studies as well as prior patent applications—whether assigned or not—that are reasonably accessible.[1] It is essential for a claimed invention to be novel, nonobvious, and “useful” (in this instance meaning usable/executable/functional) for it to be valid/enforceable.[2] And so, it is essential there be no relevant prior art showing a patent claim to be obvious or lacking novelty.
The United States Patent and Trademark Office (USPTO) Guidance details a rejection for obviousness as: “An invention that would have been obvious to a person of ordinary skill at the time of the invention is not patentable.”[3] This “person” is defined as, “The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the time of the invention.” It includes those with a professional degree of knowledge of the subject matter in question. For example, a clinical researcher in the field of gene therapy with a degree of acumen normal for that profession (PhD, involved in multiple studies, etc.), would be a person of ordinary skill in the art of DNA sequencing.
However, USPTO Guidance further clarifies that obviousness can include open-ended concepts:
And so, a claimed invention (contained in the “Claims” section of the patent application) need not be shown to be explicitly described in the prior art for it to be invalidated—it may also be invalidated if it is shown to be inherently described in the prior art.
2.2 The Doctrine of Inherent Disclosure
Patent law terms a disclosure from a prior art reference an “enabling disclosure” if it can be relied upon by one skilled in the art to anticipate the claimed invention, regardless of the particular source or country of origin.[4]
Part 2122 expounds:
A breakdown of the various phrases used to describe types of enabling disclosures in a prior art reference that can invalidate the claims of a patent application[5] are as follows:
Express (Explicit) Obviousness: This is the most apparent and easily identifiable form of enabling disclosure. For example, if a proposed invention claims a compound identical to aspirin in the year 2019, it would be invalidated as obvious due to express disclosures in prior art (many sources and publications describe the use of aspirin and the chemical makeup of aspirin well before 2019). In the sections that follow we show the vast majority of patent claims covering Vascepa to be explicitly disclosed by prior art, serving as the primary basis for our argument against the validity of Amarin’s Orange Book listed patents.
Inherent Obviousness: This type of enabling disclosure is not as directly observable in the prior art, but is implied—in other words, inherently disclosed as obvious. This could entail a scientific principle, or readily assumed result of the combination of two or more things, even if the result of the combination is not explicitly stated in the prior art. However, it cannot be termed “obvious” under § 103 if not known or understood by one of ordinary skill in the prior art at the time of the claimed invention.
Inherent disclosure (for obviousness) may in part be relied upon to refute Amarin’s method of use patent claims, which involve the absorption of eicosapentaenoic acid (EPA) to reduce serum triglyceride levels, something anyone that has ever eaten fish or taken a fish oil supplement has wittingly or unwittingly done. If Amarin were to rebut that their version of EPA is not naturally derived due to the ethyl ester form (which they did not invent), we can show this to be irrelevant, as all forms of fish and fish oil supplements have a meaningful impact on triglycerides, and importantly, ethyl ester EPA has been a known prodrug of EPA since well before the priority date of any of their patents; ethyl-EPA is acted upon by esterases in the small intestine to release free EPA, which is then incorporated into triglycerides, cholesterol esters and phospholipids. Therefore, the consumption of a highly purified ethyl ester EPA product will convert to EPA and only then be absorbed, having a lowering effect on serum TG levels. But it is the EPA itself that is actually having any effect. Thus, the enabling disclosure (“ethyl ester EPA can reduce serum triglyceride levels”) is inherently obvious to one skilled in the art.
Inherent Anticipation: In this instance, the claimed invention is found invalidated by enabling disclosure for “lacking novelty” under § 102 where a prior art reference implies the claimed use or composition, although not expressly stating it, and regardless of the knowledge of one skilled in the art. A prior art reference may inherently anticipate the claim(S) of an invention if it is necessarily present in, or the natural result of, the elements explicitly disclosed in the prior art (though not itself explicitly disclosed). For example, it may be the penultimate step that would naturally result from all prior steps, and that naturally leads to the final step that results in a product or outcome—but was not expressly stated in the literature. This anticipated disclosure invalidates a claim’s patentability for lack of novelty. And once again, it is not required that one of ordinary skill could have recognized the claimed invention (penultimate step, in our example) from the prior art disclosure.[6] That is only a requirement for an “obviousness” rejection under § 103. However, a claim can be rejected as both lacking novelty under § 102 and as obvious under § 103.
USPTO Guidance elaborates on the above, citing numerous examples from case law:
An amusing example of the above comes from Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. 529 F. Supp. 2d 106 (D. Mass. 2007), in which Ariad was rebuffed by the examiner for trying to claim a use of resveratrol for the regulation of gene expression:[7]
A rejection under inherent anticipation could be applied to Amarin’s patents, finding them wanting for novelty. The simplest of these being that ethyl ester EPA having a triglyceride-lowering effect in human subjects with severe hypertriglyceridemia was anticipated by one or more prior art references (for a novelty rejection, parts of multiple prior art references that form a whole cannot be relied upon; each must be able to stand alone as proof) showing an ethyl ester EPA + DHA formulation to have a dramatic triglyceride-lowering effect in subjects with severe hypertriglyceridemia. Although the isolation and dosing of ethyl ester EPA alone (with very little DHA) having a TG-lowering effect isn’t explicitly shown in such a reference, the TG-lowering effect of its isolated use is inherently anticipated by it, being prominently included in the compound, and thus such a use is lacking novelty.
(Please note that the courts’ definition of what is novel and nonobvious is separate from and more stringent than FDA regulation on what is entitled to 5-year NCE status, where a one-to-one active ingredient to active moiety is required for refusal.[8])
As we will further prove in the sections that follow, there is much compelling evidence that very little that is novel can be claimed from ethyl ester forms of purified fish oil, regardless of the ratio of EPA to other fatty acids contained therein (since the early ‘90s), and regardless of the indications for use (since the mid-late ‘90s).