The PTAB issued a final written decision in IPR2016-00006, holding claims 1–22 of U.S. Patent No. 8,497,393 (“the ’393 patent”) unpatentable under 35 U.S.C. § 102(b) and 35 U.S.C. § 103(a). All of the claims are product-by-process claims to prostacyclin derivatives including treprostinil, the active ingredient in the pulmonary arterial hypertension drug Remodulin®.

Claim 1 recites:

1. A product comprising a compound of formula I [formula I omitted] or a pharmaceutically acceptable salt thereof, wherein said product is prepared by a process comprising

a) alkylating a compound of structure II with an alkylating agent to produce a compound of formula III [formulas II and III omitted],

wherein [recitation of Markush groups for the specified structures],

b) hydrolyzing the product of formula III of step (a) with a base,

c) contacting the product of step (b) with a base B to form a salt of formula Is [formula Is omitted], and

d) optionally reacting the salt formed in step (c) with an acid to form the compound of formula I.

The petitioner, SteadyMed LTD (“SteadyMed”) challenged claims 1–5, 7–9, 11–14, and 16–20 as being anticipated by WO 2005/007081 by Phares (“Phares”). The patent owner, United Therapeutics Corporation (“UTC”), did not dispute that Phares discloses treprostinil diethanolamine product as claimed in the ’393 patent. Instead, UTC argued that the treprostinil produced according to Phares exhibited differences in overall purity and its impurity profile compared to treprostinil produced according to the challenged claims, and, thus, Phares cannot anticipate the claimed product.

The PTAB sided with SteadyMed. The PTAB acknowledged that the general rule when determining patentability of a product-by-process claim is to focus on the product and not on the process of making it, however, an exception applies when process steps recited in the claim impart “structural and functional differences” to the claimed product. The PTAB found that the process steps recited in the challenged claims do not impart structural or functional differences to the claimed product, and, therefore, did not award any patentable weight to the process steps.

The treprostinil diethanolamine salt produced according to Phares was of at least equal purity to that produced by the ’393 patent. Since the Phares treprostinil product was at least as pure as the ’393 batches and was not structurally or functionally different from the claimed product, Phares anticipated the ‘393 patent claims.

The inventors overcame the “Moriarty” prior art reference during prosecution, which also produced trepostinil. They distinguished trepostinil prepared according to the Moriarty prior art method since that product allegedly contained impurities not found in the trepostinil prepared according to the ’393 patent claims. According to the PTAB, the inventors did not clearly disclaim or disavow the full scope of the claims to exclude the Moriarty trepostinil since they did not identify a specific impurity profile for the Moriarty treprostinil. Moreover, due to batch-to-batch variation in the Moriarty product, the inventors likely would not have been able to define any specific impurity profile. In addition, the PTAB found that the difference in treprostinil prepared using the different methods is likely due to batch-to-batch variation, meaning that the claimed treprostinil is structurally and functionally the same as the Moriarty treprostinil. The PTAB further noted that the record does not contain evidence of any clinical or safety differences between Moriarty treprostinil and treprostinil produced according to the ’393 patent.

SteadyMed challenged the remaining claims as being obvious over Phares, Moriarty, and two other references. In response, UTC mainly argued that treprostinil made according to the claimed process contains fewer impurities than treprostinil produced by other methods, which the PTAB quickly dismissed as not being supported by the record (as discussed above). Nevertheless, the PTAB addressed UTC’s long-felt need arguments and held that, even crediting UTC’s contention that the FDA seeks to minimize all impurities in all pharmaceuticals to the extent possible, such a general agency preference for improved purity is insufficient to establish a long-felt but unmet need for improved treprostinil specifically.

Takeaway:

Product-by-process claims may be vulnerable to anticipation and obviousness challenges, especially when the claimed product differs from the prior art products only in the level of purity and/or in its impurity profile.