By Andrew Williams --
Earlier this week, the Patent Trial and Appeal Board ("PTAB" or "Board") handed down what is thought to be the first set of inter partes review ("IPR") Final Written Decisions ("FWDs") in the biopharmaceutical industry. And unlike the case of the first set of Orange-Book related FWDs (see "PTAB Update -- Hatch-Waxman-Watch Edition"), the Board determined that all challenged claims were unpatentable. The drug that these patents covered is Myozyme, or alglucosidase alfa, which is an enzyme replacement therapy for treating Pompe disease (or glycogen storage disease type II). This disease is caused by a deficiency of the lysosomal enzyme acid α-glucosidase ("GAA"), resulting in an accumulation of glycogen in tissues such as the heart and skeletal muscle. Pompe disease is treated by administering to the patient a therapeutically effective amount of the protein. Myozyme is a recombinant human version of this protein (rhGAA), and is produced in precursor form in Chinese hamster ovary (CHO) cell cultures. The drug is marketed by Genzyme, the patent owner of two related patents involved in these IPR proceedings. The third related to an unrelated patent, which is owned by Duke University. BioMarin Pharmaceutical Inc. filed the three petitions in 2013. The PTAB determined that the claims of the two Genzyme patents were obvious in view of various combinations of references, including a Duke Press Release announcing the FDA's approval of an application for Orphan Drug Designation, a PCT application disclosing the production of phosphorylated lysosomal proteins using transgenic mammals, and three other references reporting research related to GAA. In addition, the PTAB determined that the claims of the Duke patent were either obvious in view of similar cited art, or were anticipated by the oldest Genzyme patent involved in these proceedings. It is unclear if there are other patents that cover this product, but Genzyme has at least one continuing application pending at the Office. In today's post, we will take a closer look at these first two IPR proceedings related to the Genzyme patents.
IPR2013-00534 and IPR2013-00537
The patents related to the first two IPR petitions related to methods of treating human patients afflicted with Pompe disease by intravenously administering a therapeutically effective amount of Human GAA in order to reduce and/or arrest further accumulation of glycogen. The patents at issue were U.S. Patent Nos. 7,351,410 and 7,655,226. The '410 patent only has one claim:
1. A method of treating a human patient with Pompe's disease, comprising intravenously administering biweekly to the patient a therapeutically effective amount of human acid alpha glucosidase, whereby the concentration of accumulated glycogen in the patient is reduced and/or further accumulation of glycogen is arrested.
Claim 1 of the '226 patent is similar, except it does not contain the limitation for biweekly administration.
The '410 patent was invalidated on two separate obviousness grounds. The first was in view of the combination of Reuser (WO 97/05771), Barton (a New England Journal of Medicine article from 1991), and Van der Ploeg (a Pediatric Research journal article from 1988). Reuser was described as teaching "the production of phosphorylated lysosomal proteins using transgenic nonhuman mammals for use in enzyme replacement therapy as treatment for lysosomal enzyme deficiencies." This reference mentioned that a Pompe disease treatment in mice had been tested with a purified GAA, and that pharmaceutical compositions for intravenous administration were contemplated by the reference. Barton was cited as teaching a clinical trial with Gaucher Disease (another lysosomal enzyme deficiency disease), wherein patients received enzyme replacement therapy on a biweekly intravenous administration schedule. Finally, van der Ploeg allegedly described "an in vitro study using cultured skeletal muscle cells from a patient with Pompe disease." The Patent Owner argued that "a person of ordinary skill in the art would not have had a reasonable expectation of success for a method of treating a human patient with Pompe disease using GAA administered biweekly . . . ." Moreover, it argued that there would have been no motivation to combine because of the differences between Gaucher disease and Pompe disease. Finally, the Patent Owner alleged that the objective indicia of non-obviousness supported the patentability of the claim.
The Board did agree that as of the priority date, it could not have been predicted with "absolute certainty" that Pompe disease could be treated safely and effectively using GAA. However, they also concluded that there was sufficient motivation to pursue the clinical development of treatment as disclosed in Reuser. The only missing element was the biweekly dosing schedule. But, because the experimentation needed to achieve this treatment regime was "nothing more than" routine, it required skills more akin to an artisan rather than an inventor. Important in the Board's analysis was that the prior art did not merely teach a promising field of experimentation with numerous parameters to try, but instead provided sufficient motivation to select a suitable dose and dosing schedule. And, because the enzyme replacement therapy would have needed to be administered for life, a repeated spaced administration of GAA would have been understood.
With regard to the secondary considerations, the Board found a nexus lacking between the evidence related to long-felt but unmet need, skepticism, praise, and commercial success. This was because the Board characterized the invention as limited to the biweekly administration feature. Therefore, because the secondary considerations related to the merits of the therapeutic compositions of GAA, they were inapplicable to the present invention. This seems to be an unfair characterization of the invention, however, because even if such compositions were known, they were not being used as a safe and effective treatment of Pompe disease (including the biweekly administration schedule).
The other obviousness argument combined Barton and Van der Ploeg with a Duke Press Release announcing the approval of an Orphan Drug application for the GAA drug. This release is described as providing "details [of] a proposed FDA clinical trial study in which infants with Pompe disease would be injected with recombinant GAA to evaluate the safety and efficacy of the recombinant enzyme treatment." Genzyme had argued that the Press Release was silent as to the dosing regimen, and therefore the cited art did not contain all of the limitations of the claim. However, the Board found the use of the term "injected" to teach "intravenous administration." Also, the Press Release did not disclose the source of the enzyme, but the Board found this was cured by Van der Ploeg. In other words, "the concept of using human GAA to treat Pompe disease was known in the art." And, even if clinical trials were unpredictable, their design was essentially routine to those skilled in the art.
The IPR related to the '226 patent was similar in nature. In fact, it was essentially easier to establish the obviousness of the claims because they did not contain the limitation related to the dosing regimen. Therefore, because this important impediment was removed, institution was only sought and granted on obviousness challenges incorporating the Duke Press Release. And, not surprising in view of the other IPR FWD, all challenged claims were found to be unpatentable.
In a future post, we will analyze the FWD related to the Duke patent.