The Patent Trial and Appeal Board (“PTAB”) recently sided with petitioner BioMarin Pharmaceutical in three inter partesreview proceedings involving Genzyme’s enzyme therapy product Myozyme®. The decisions mark one of the first times that the PTAB has invalidated a pharmaceutical patent in the context of an inter partes review. Cf., e.g., Gnosis Spa v. S. Ala. Med. Sci. Found., IPR2013-00116 (P.T.A.B. June 20, 2014).

Genzyme’s Myozyme® is an injectable acid alpha glucosidase (“GAA”) enzyme approved for treatment of Pompe disease. California-based biotechnology company BioMarin is developing a fusion-protein of insulin-like growth factor 2 and GAA for the treatment of the same condition.

In August 2013, BioMarin filed petitions for inter partes review of Genzyme’s U.S. Patent Nos. 7,351,410 and 7,655,226. BioMarin also filed a petition for inter partes review of U.S. Patent No. 7,056,712, which was assigned to Genzyme collaborator Duke University. All three challenged patents relate to methods of treating Pompe disease by administering human GAA. 

In its Final Written Decisions, which issued on February 23, 2015, the PTAB found that all of the challenged claims are unpatentable. 

In the Genzyme cases, the PTAB held that the challenged claims were obvious over a combination prior art references. Genzyme did not dispute the PTAB’s finding that the prior art disclosed every limitation of the challenged claims. However, Genzyme argued that a person of ordinary skill would not have had a motivation to combine the references to arrive at the claimed “biweekly” dosing schedule. The PTAB rejected this argument, stating that “the preponderance of the evidence establishes that the selection of the dose and dosing schedule would have been a routine optimization of the therapy outlined in [the prior art,] which would have been achievable through the use of standard clinical trial procedures.”

Genzyme also argued that a person of ordinary skill would not have had a reasonable expectation of success that administration of GAA would achieve the claimed result of reducing “the concentration of accumulated glycogen in the patient” and/or arresting “further accumulation of glycogen.” The PTAB rejected this argument as well, noting that the argument was premised on an improper construction of the term “glycogen in the patient” that the PTAB had rejected. The PTAB went on to explain that “a reasonable expectation of success does not require absolute predictability” and concluded that it would have been routine for “a person of ordinary skill in the art, to verify the expectation that a specific dosage (within a previously suggested dosage range) and corresponding dosage regimen would have been safe and effective.”

In the Duke case, the PTAB held that the challenged claims were anticipated by and obvious over the prior art. The obviousness dispute largely turned on whether a person of ordinary skill would have been motivated to combine the primary reference, which pertained to human GAA produced in transgenic animals, with references pertaining to human GAA produced in chinese hamster ovary cell cultures. The PTAB found that a person of ordinary skill would have been motivated to make this combination and that the claimed methods employing GAA “produced in chinese hamster ovary cell cultures” were obvious.

The Myozyme® patents are just three of a growing number of pharmaceutical patents subject to inter partes review proceedings. Although pharmaceutical patents still make up a small percentage of pending IPRs, the Myozyme® cases make clear that IPR proceedings warrant the attention of patent owners and would-be challengers alike.