IP Law Daily Enzyme treatment method for Pompe disease unpatentable as anticipated
Tuesday, April 25, 2017

Enzyme treatment method for Pompe disease unpatentable as anticipated

Substantial evidence supported a Patent Trial and Appeal Board finding that both independent claims of a Duke University patent for a method of treating Pompe disease were unpatentable as anticipated by a prior art patent, the U.S. Court of Appeals for the Federal Circuit. The prior patent described use of the same enzyme in the same amounts and at the same dosage intervals as the method disclosed in the independent claims. The Board erred, however, in concluding that two dependent claims were unpatentable because the Board applied an incorrect construction of the claim term "precursor." The case was remanded for further proceedings to determine whether one of the dependent claims was obvious in light of a combination of prior art, under the proper claim construction (Duke University v. BioMarin Pharmaceutical Inc., April 25, 2017, Lourie, A.).

Patent at issue. Duke’s patent, U.S. Patent 7,056,712 ("the’712 patent"), was directed to methods for treating glycogen storage disease type II (“GSD-II” or “Pompe disease”) using enzyme replacement therapy. Pompe disease is a genetic disorder affecting muscles caused by a deficiency of acid α-glucosidase (GAA), a lysosomal enzyme that breaks down glycogen. The disease most seriously affects the cardiac and skeletal muscles and in its most severe form, infantile Pompe disease, frequently causes sufferers to die of cardiac failure by one year of age. The ’712 patent described the successful treatment of three infants suffering from infantile Pompe disease by administering recombinant human GAA (rhGAA) twice weekly to the infants. The rhGAA was produced in Chinese hamster cell ovary (CHO) cell structures. The treatment method and the method of producing the rhGAA were described in independent claims 1 and 20. Dependent claim 9 added the limitation "wherein the human acid α-glucosidase is a precursor of recombinant human acid α-glucosidase that has been produced in chinese [sic] hamster ovary cell cultures" (emphasis added). Dependent claim 18 added, “wherein the human acid α-glucosidase is administered in conjunction with an immunosuppressant.” Dependent claim 19—which depended from claim 18—further added "wherein the immunosuppressant is administered prior to any administration of human acid α-glucosidase to the individual" (emphasis added).

IPR proceeding. BioMarin Pharmaceutical Inc. filed a petition for inter partes review (IPR) of claims 1-9, 11, 12, 15, and 18-21 of the ’712 patent. The Board instituted review and held that the challenged claims were unpatentable as anticipated by a prior art patent ("van Bree") and/or as obvious over an international patent application ("Reuser") in view of a journal article ("Van Hove") either alone or in combination with other references, in particular a journal article referred to as "Brady".

Prior art. van Bree and Reuser disclosed methods of producing rhGAA in transgenic mammals and its use in enzyme replacement therapy to treat Pompe disease. Van Hove taught a method for purifying large quantities of rhGAA expressed in CHO cells for use in Pompe disease enzyme replacement therapy. Brady disclosed administering an immunosuppressant to treat an immune response to enzyme replacement therapy in the treatment of Gaucher disease with Ceredase.

Anticipation. The Board found that van Bree anticipated claims 1-9, 12, 15, 20, and 21. The Board found that van Bree "describes administering hGAA produced in CHO cell cultures to patients in the same manner, i.e., using the same amounts and dosage intervals, as described for hGAA produced in transgenic animals." The Board’s conclusion was guided by its construction of "precursor," which encompassed administering both precursor and non-precursor forms of rhGAA at the same time, and was not limited to administering exclusively a precursor form and no other form.

With respect to independent claims 1 and 20, the court affirmed the Board’s decision, holding that the Board’s anticipation findings were supported by substantial evidence. In the court’s view, the disclosure in van Bree supported the finding that its teachings applied to GAA produced in CHO cell cultures. Statements in van Bree provided a basis for the Board’s conclusion that van Bree described administering human GAA produced in CHO cell cultures to patients in the same manner—that is, using the same amounts and dosage intervals—as described for human GAA produced in transgenic animals. Expert testimony was not necessary to support the anticipation determination, the court said. Duke did not argue that the dependent claims (other than claim 9) could be patentable on their own if the independent claims were unpatentable; therefore, the anticipation decision with respect to those claims was also affirmed.

However, the court reversed the Board’s finding that dependent claim 9 was anticipated. In the court’s view, the Board’s construction of "precursor" was flawed, and the proper construction was "exclusively a precursor of recombinant hGAA that has been produced in CHO cell cultures." Under this construction, van Bree did not disclose a "precursor" because it did not disclose administering exclusively a precursor of rhGAA produced in CHO cell cultures.

Obviousness. The Board also concluded that claims 1-9, 11, 12, 15, and 18–21 were unpatentable as obvious. The Board found that a skilled artisan would have had reason to combine the teachings of Reuser and Van Hove because "both discuss[] rhGAA produced in CHO cells and methods of treating Pompe disease." Because of the court’s holding on anticipation, the only remaining issue to decide was whether claims 9 and 19 were unpatentable as obvious. The court reversed the Board’s obviousness determination with respect to claim 19 and vacated the obviousness determination with respect to claim 9. The court remanded the case for reconsideration of the parties’ arguments regarding claim 9 under the correct construction of "precursor".

The court agreed with Duke’s argument that the Board’s claim 19 obviousness determination was legally deficient and the underlying fact-finding was not supported by substantial evidence because it rested on cursory and conclusory expert testimony. According to the court, substantial evidence did not support the Board’s finding that "the prophylactic administration of an immunosuppressant would have been a predictable variation of the use of immunosuppressant disclosed in Brady." Brady did not disclose administering immunosuppressant prior to any and all administration of hGAA, as required by claim 19. The expert testimony relied on by the Board to bridge the gap between the disclosure in Brady and claim 19 fell short of what would have rendered the subject matter of the claim obvious, the court said. The testimony did not address what an ordinary artisan would have done or understood regarding prophylactic administration of immunosuppressants in the context of GAA enzyme replacement therapy prior to the priority date of the ’712 patent. Therefore, the obviousness finding as to claim 19 was reversed.

The case is No. 2016-1106.

Attorneys: Steven A. Zalesin (Patterson Belknap Webb & Tyler LLP) for Duke University. Gerald Myers Murphy, Jr. (Birch Stewart Kolasch Birch LLP) for BioMarin Pharmaceutical Inc.

Companies: Duke University; BioMarin Pharmaceutical Inc.

MainStory: TopStory Patent FedCirNews

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