The Coalition for Affordable Drugs, the group controlled by billionaire J. Kyle Bass’ hedge fund Hayman Capital and IP Navigation Group owner Erich Spangenberg, filed another new petition for inter partes review of a patent for treating multiple sclerosis owned by Biogen MA Inc.
The Sept. 28 petition cites prior art not previously considered by the Patent Trial and Appeals Board in a previous petition filed by the Bass and Spangenberg-led coalition, which was rejected because of unpersuasive prior art.
This new petition also takes criticizes Biogen and other drug compaanies for so-called “evergreening,” the practice of seeking to extend patents beyond the original 10 to 20 years by asking the U.S. Patent Office to approve patents for incremental innovations such as for different dosage amounts.
The coalition previously raised the issue of evergreening in the first petition against the ‘514 patent as well as in a petition against Vimovo.
Spangenberg also said on Friday on his blog that he plans to publish though not file substantially complete IPR petitions of other weak drug patents where evergreening is involved.
The patent at issue in the new petition is 8,399,514, entitled treatment for multiple sclerosis, which was assigned from Biogen IDEC MA Inc. to Biogen MA in March 2015.
“The ‘514 patent is an example of evergreening, a business strategy by which companies with patents that are about to expire retain their monopolies for longer than would normally be permitted under law by taking out new patents, e.g., claiming associated delivery systems or new drug mixtures. Evergreening is one reason why MS drug prices are so high;
see Hartung et al. (Ex. 1029) and Hendricks, “The Rise of Big Generic: Why Knockoff Prescriptions Now Cost $1,200” (Ex. 1044).
The challenged ‘514 patent is the second Biogen patent which claims a method for treating multiple sclerosis using dimethyl fumarate or DMF. The first one was U.S. Patent No. 7,320,999, entitled dimethyl fumarate for the treatment of multiple sclerosis, also known as Joshi et al, filed July 17, 2002, published on January 23, 2003.
The innovation claimed in the ‘514 patent is a 480 mg per day dosage of dimethyl fumarate, or DMF. The previous effective dosage claimed was 720 mg per day.
The coalition’s petition asserts that Biogen convinced the PTO that person of ordinary skill in the prior art would not have thought to test a lower dosage of DMF and that that was an error.
“On August 3, 2012, applicants asserted that Kappos 2006 suggested that the amount of DMF ‘required’ for relapsing remitting multiple sclerosis (RRMS) activity is 720 mg/day, e.g., ‘(b) The 720 mg/day dose was expected to be required for clinical effectiveness'."
Kappos 2006, however, one of the prior art citations noted by the coalition, disclosed a dose ranging study using BG00012, at three dose levels: 120 mg per day, 360 mg per day and 720 mg per day.
Kappos 2006 found that only the 720 mg per day dose was effective, thus producing only a single dose-response data point.
Biogen argued that a person of ordinary skill in the prior art would not test a lower dose than 720 mg/day, even while conceding that there were good reasons to try.
Those reasons include that the side effects associated with chronic, lifelong treatment are generally dose-related, so a 480 mg/day dose would be expected to have fewer side effects than a 720 mg/day dose.
“Why, then, wouldn’t a POSITA try a lower dose? According to the applicants, simply because the 720 mg/day dose had worked.”
The petition notes that the coalition’s previous petition, which was denied, cited different prior art.
The new prior art in the new petition includes the above mentioned Kappas 2006 citation, as well as a declaration in ClinicalTrials NCT00168701; the aforementioned Joshi patent and the International Conference on Harmonization of Pharmaceuticals for Human Use —dose response information to support drug registration E4.
“Kappos 2006 discloses the results of a double-blind Phase II clinical trial for treating multiple sclerosis with ‘BG00012’ administered orally at three dose levels.
“ClinicalTrials NCT00168701 (Ex. 1022) discloses a dose-ranging Phase II clinical trial protocol using ‘DMF [dimethyl fumarate] the active ingredient in BG00012’. The protocol states that intolerance of BG00012 as determined by flushing episodes and gastrointestinal (G.I.) disturbances may be a problem for patients, and dose reductions are specified.
Joshi refers to the U.S. patent disclosing that DMF is therapeutically effective against autoimmune diseases including multiple sclerosis.
Finally, the ICH Guideline E4 teaches that dosing studies are conducted as standard procedure in drug development in order to establish proper dose ranges.
Kappas 2006 previously wasn’t known to the coalition at the time it filed its first petition to invalidate the ‘514 patent. It became available after the PTAB issued a ruling in an interference action filed by Forward Pharma that held that the ‘514 patent was not entitled to priority date of February 8, 2008 rather than Feb. 8, 2007.
Officials of Biogen couldn't be reached immediately for comment.
George Goodno, a spokesman for the Biotechnology Industry Organization in Washington, D.C., said he was aware of the new petition but declined to comment further.
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