Can Celgene protect Revlimid® from Dr. Reddy's generic?
Life is complicated, and so is patent litigation. But sometimes, it’s not. We previously published on the recent onslaught of new generics vying to distribute a generic version of Revlimid®. Leading the pack is Dr. Reddy’s, and although Celgene has asserted numerous patents against Dr. Reddy’s proposed generic, a single issue has crystallized that could make or break the case.
Celgene has asserted numerous patents, which generally fall into two categories: polymorph patents and indication patents (method-of-use patents). The indication patents mostly expire by 2022, whereas the two polymorph patents, the ‘800 patent and the ‘217 patent, will not expire until 2027 and 2024, respectively. Thus, Celgene’s big stick in this fight are the polymorph patents. Successfully prevailing on those patents is a mechanism to keep out generics well past 2022, or as a leverage to extract a better settlement of an entry date.
The polymorph patents are directed to “crystalline” lenalidomide. Dr. Reddy’s claims it does not infringe this patent because its generic version of Revlimid® is amorphous. The parties recently filed briefs in advance of an upcoming Markman decision, thus revealing the arguments on both sides. In those briefs, they dispute a single issue regarding the polymorph patents, and the issue is fairly straightforward: how should the word “crystalline” be construed, or interpreted, by the Court? Who has the better argument?
Celgene’s opening claim construction brief is not more than five pages, itself a commendable feat of judicious restraint. The unstated takeaway is that this issue is so simple, there’s really not much to say about it. Celgene argues that the word “crystalline” does not require a special, or convoluted, definition. Rather, it should be interpreted according to its “plain and ordinary meaning,” which is patent-lawyer-speak for, it means what it says, and everybody already knows what it means. Celgene writes, “the claims require ‘crystalline [lenalidomide] hemihydrate.’ Thus, it is not necessary for the Court to construe the term . . . .”
By contrast, Dr. Reddy’s proposes a unique interpretation of “crystalline” to mean that, the solid form of the molecules are organized in a specific way, and have “a regularly repeating three dimensional pattern” that has “long-range order.” Dr. Reddy’s also argues that to identify the crystalline form of the claimed polmorph, there are well-known techniques to do so, such as X-ray powder diffraction (XRPD). Thus, the claimed polymporh should be identifiable by these techniques.
The same compound can have different crystal structures. The different crystals formations are known as “polymorphs,” which happens when the molecules arrange differently, as shown below. (This figure was taken from Dr. Reddy’s opening claim construction brief, Celgene v. Dr. Reddy’s, Civil Action No. 2:16-cv-7704 (Dkt. 67) p. 4).
Dr. Reddy’s argues that materials can be “crystals” or “amorphous.” To be crystal, according to Dr. Reddy’s, necessarily means there is a repeating, periodic order for how the individual molecules are arranged, or packed, together. By contrast, “amorphous” materials have molecules that are randomly oriented with no long-range order. This principle is illustrated below, which Dr. Reddy’s argues is a crystalline form of silicon dioxide on the left, and an amorphous form of the same molecule on the right. (See Celgene v. Dr. Reddy’s, Civil Action No. 2:16-cv-7704 (Dkt. 67) p. 5).
A lot of patent-litigation disputes devolve into a battle of the experts. But this one may not. Dr. Reddy’s brief is longer, and delves deeper into the science of polymorphs and crystal structures, but there may not be much there that Celgene will necessarily dispute. (That, itself, remains to be seen. The parties are currently conducting expert discovery on this issue, and will file responsive Markman briefs in early March 2018.)
Instead, rather than being about the science, this dispute may turn on rote, legal claim-construction principles, which dictate how to interpret a patent. The patents recite that the claimed polymporphs must be “crystalline,” and Celgene cannot escape that. That does not mean, however, that Celgene should concede to Dr. Reddy’s narrow definition of what “crystalline” means. Celgene argues that the patents never define the word “crystalline” with the precise limitations pushed for by Dr. Reddy’s. This includes, for instance, the requirement that the molecules are arranged in a “regularly repeating, three-dimensional pattern with long-range order.” Nor do the patents, according to Celgene, require specific techniques for identifying whether an infringing molecule is crystalline. Celgene’s basic point is these limitations are not required by the patent, and hoisting them onto the claims would unfairly make it easier for Dr. Reddy’s to evade infringement.
By contrast, Dr. Reddy’s argues that the science dictates its definition of “crystalline,” and nothing in its definition is at odds or inconsistent with the general understanding of scientists on this point. Moreover, Dr. Reddy’s makes a strong point that Celgene cannot evade the dispute altogether by throwing its hands in the air and arguing that the word “crystalline” just means what it says. Instead, according to Dr. Reddy’s, the parties are clearly disputing the scope of the word “crystalline,” and even if Celgene cannot commit to a definition, the Court needs to adopt one.
That last issue is really the one that the Court will have to wrangle with. Courts often hold that disputed claim terms do not require an explicit construction, and are therefore given their “plain and ordinary meaning.” And unfortunately, there are no bright line rules for when a term must be construed versus when it should not be. Here, the most important issues appears to be whether the claimed “crystalline” polymorphs can be amorphous. It’s possible that the Court answers this precise question only, while simultaneously rejecting Dr. Reddy’s narrow construction, and also rejecting Celgene’s proposed non-construction. Instead, it may craft its own middle-ground.
As mentioned above, more briefing on this issue is expected in early March 2018. In addition, hearing the Court’s comments and questions during the Markman hearing will provide deeper insight into the outcome of this dispute.