BSKB ASSISTS CLIENT IN SUCCESSFUL IPR CHALLENGES TO BIOPHARMACEUTICAL PATENTS FOR TREATING POMPE DISEASE

by Gerald M. Murphy, Jr. | BSKB News

BSKB partners, Gerald M. Murphy, Jr. and MaryAnne Armstrong, Ph.D., are pleased to announce that on November 9, 2020, the U.S. Supreme Court denied a petition for certiorari  filed by Duke University  requesting appeal from a decision from the Court of Appeals for the Federal Circuit (CAFC), which had been decided in favor of BSKB's client, BioMarin Pharmaceutical Inc. Duke Univ. v. BioMarin Pharm., Inc., No. 19-1475, 2020 U.S. LEXIS 5471 (Nov. 9, 2020) The patent at issue relates to the treatment of Pompe disease by enzyme replacement therapy.

Previously on October 11, 2019, the CAFC issued a decision affirming the PTAB's decision that claim 9 of a patent owned by Duke University was obvious over the prior art. This decision was the culmination of three inter partes reviews ("IPR") which challenged three patents. The IPRs were the first-ever IPRs filed against biopharmaceutical patents. More information regarding the multiple PTAB decisions, prior CAFC decisions relating to the patents is provided below.

In 2013, three IPRs were filed on the same day against two patents owned by Genzyme Therapeutic Products, and one patent owned by Duke University, which was licensed to Genzyme. In February 2015, the PTAB held that all of the challenged claims of two patents owned by Genzyme (IPR2013-00534 and IPR2013-00537) and one patent owned by Duke University (IPR2013-00535) were invalid over prior art. But, the story continues. All of the decisions were eventually appealed to the CAFC.

The appeals from the Final Written Decisions ("FWD") in the two Genzyme IPRs were the first to reach the CAFC. In 2016, the CAFC affirmed the two decisions in a consolidated decision. Genzyme Therapeutic Prods. L.P. v. BioMarin Pharm. Inc., 825 F.3d 1360 (Fed. Cir. 2016). One of the important issues addressed by the CAFC was the type of evidence that the PTAB can rely on in a Final Written Decision. Genzyme argued that the PTAB could only rely on references that were actually discussed in the Institution Decision as being relevant to an instituted ground and the PTAB could not rely on other references, discussed in the Petition, that were part of non-adopted "redundant" grounds. Relying heavily on the Administrative Procedure Act ("APA"), the CAFC noted that the PTAB did not change theories mid-stream and that at the stage of the Institution Decision, the "Board cannot predict all the legal or factual questions that the parties may raise during the litigation." Thus, in a Final Written Decision, the PTAB can rely on various references, including "redundant" references, to explain the state of the art and to support its decision. Genzyme filed a Request for Panel Rehearing and Rehearing En Banc, which was denied on September 26, 2016. The CAFC Decision from the consolidated appeals was listed by Law360 in "A Look Back at the Top AIA-Related Decisions of 2016." The article is available to Law360 subscribers here.

The appeal in the Duke IPR was next to reach the CAFC. The CAFC appeal was delayed because Duke filed a Request for Rehearing with the PTAB with respect to claim 19. On April 25, 2017, the CAFC affirmed the finding that all but two claims were invalid. The CAFC reversed the finding of obviousness of claim 19 and reversed and remanded the finding of obviousness of claim 9, because the PTAB had wrongly interpreted claim 9. Duke Univ. v. BioMarin Pharm. Inc., 685 F. App'x 967 (Fed. Cir. 2017). Claims 1 and 9 of the Duke patent read:

1. A method of treating glycogen storage disease type II in a human individual having glycogen storage disease type II, comprising administering to the individual a therapeutically effective amount of human acid α-glucosidase periodically at an administration interval, wherein the human acid α-glucosidase was produced in Chinese hamster ovary cell cultures.

9. The method of claim 1, wherein the human acid α-glucosidase is a precursor of recombinant human acid α-glucosidase that has been produced in Chinese hamster ovary cell cultures.

The PTAB interpreted claim 9 broadly in its first decision when it held that claim 9 was obvious. The CAFC agreed with Duke's argument for a narrower interpretation, as follows:

On this point, we disagree with the Board's construction and agree with Duke that the proper construction of "precursor" in claim 9 is "exclusively a precursor of recombinant hGAA that has been produced in CHO cell cultures." Claim 9 requires that "the [hGAA] is a precursor" and refers to claim 1 for the antecedent basis of "the [hGAA]." '712 patent col. 13 ll. 9-12 (emphases added). That sentence structure makes clear that the "is a precursor" phrase limits the form of hGAA to a precursor form. The claim language and structure thus support the conclusion that "the [hGAA]" in claim 9 is exclusively a precursor of hGAA.

After remand to the Board, the PTAB issued a Supplemental Final Written Decision ("SFWD") on January 17, 2018, based on the claim interpretation indicated by the CAFC and after considering the arguments of both parties, including evidence of secondary indicia of obviousness. The SFWD of the PTAB held:

… “we conclude that the preponderance of evidence establishes that a person of ordinary skill in the art would have had reason to administer exclusively a precursor of recombinant hGAA from CHO cells to treat GSD-II.”

The SFWD was again appealed to the CAFC by Duke and during the CAFC briefing, BioMarin argued that the evidence established that since the precursor was known to be the active form and that the mature form was known not to be active, it would be obvious to purify the precursor before administering to patients. Duke disagreed with this argument, and further argued that the commercial success enjoyed by this product, including the fact that it was the first FDA approved drug for a fatal disease, compelled a finding of non-obviousness. On October 11, 2019, after hearing oral arguments, the CAFC affirmed the decision of the PTAB per curiam. Duke Univ. v. BioMarin Pharm. Inc., No. 2018-1696, 2019 U.S. App. LEXIS 30468 (Fed. Cir. Oct. 11, 2019). On July 2, 2020, Duke filed a Petition for Writ of Certiorari at the Supreme Court. The Supreme Court denied Duke's Petition on November 9, 2020. Duke Univ. v. BioMarin Pharm., Inc., No. 19-1475, 2020 U.S. LEXIS 5471 (Nov. 9, 2020).

 The commercialization of the technology underlying the Genzyme and Duke Patents was assisted by John Crowley, the father of two children diagnosed with Pompe disease. Mr. Crowley invested his life savings in a biotechnology start-up company in a search for a treatment for his children. The story behind the father's efforts is the subject of a book, The Cure: How a Father Raised $100 Million – And Bucked the Medical Establishment – In a Quest to Save His Children, published in 2006, and was the inspiration behind the movie Extraordinary Measures, released in 2010, starring Harrison Ford. A YouTube link to the movie trailer is provided here.