A set of three gummy letters in the shape of X isolated on white

In a series of unfortunate events for Teva Pharmaceuticals, three patents covering methods for administering the blockbuster multiple sclerosis (MS) drug Copaxone® (glatiramer acetate) (owned by Yeda Research and Development Co.) were struck down by the PTAB in recent IPR decisions (IPR2015-00830, IPR2015-00643, and IPR2015-00644).  These patents are directed to methods for administering Copaxone in a 40 mg dosage form, 3 times per week to treat relapsing-remitting MS:  U.S. Patent Nos. 8,232,250, 8,399,413 and 8,969,302.  Illustrative claim 1 of the ’413 patent reads as follows:

  1. A method of reducing the frequency of relapses in a human patient suffering from relapsing-remitting multiple sclerosis or a patient who has experienced a first clinical episode and has MRI features consistent with multiple sclerosis comprising administering to the human patient a therapeutically effective dosage regimen of three subcutaneous injections of 1 ml of a pharmaceutical composition comprising 40 mg of glatiramer acetate over a period of seven days with at least one day between every subcutaneous injection, the regimen being sufficient to reduce the frequency of relapses in the patient.

Mylan Pharmaceuticals filed separate IPRs challenging the claims of each of the Teva patents as anticipated by or obvious over certain prior art.  The PTAB instituted an IPR for each patent on the grounds of obviousness over 3 pieces of cited art, which were the same for all challenged patents: (1) Pinchasi, a 2007 patent publication (assigned to Teva); (2) a 1996 Summary Basis of Approval (SBOA) by the FDA for Copaxone; and (3) Flechter, an article that describes a clinical trial of a Copaxone 20 mg dosage.

Interestingly, the cited references are all directly related to work carried out with Copaxone, and two of the references relate to Teva’s own work, in particular Teva’s clinical trials with an earlier version of Copaxone, a 20 mg dosage form.  For example, the Petitioner cited a recommendation from the FDA in the 1996 SBOA for Copaxone that suggests that the approved 20 mg dosage form should be investigated for efficacy when administered at lower frequencies than the approved daily administration, e.g., when given on alternate days.  Flechter describes a clinical trial in which a 20 mg dose of Copaxone was administered every other day to patients with relapsing-remitting MS, and discloses that administration on alternate days compared favorably with daily administration.  Pinchasi describes administration of a 40 mg dose of Copaxone and suggests that the administration could be daily or every other day.

The Patent Owner (PO) argued that treatment on alternate days was not the same as the regimen recited in the claims, which was directed to administration 3 times per week with at least one day between treatments, e.g., administration on every Monday, Wednesday and Friday, and that such a regimen was not suggested in the cited art.  The PO also presented evidence of secondary considerations of non-obviousness, citing unexpected results of the present treatment, commercial success of the 40 mg dosage form, and the long-felt need for a treatment with improved convenience and the desired safety profile.

The Board agreed with Petitioner that the suggestions to reduce dosing frequency and the apparent forgivingness of missing doses of Copaxone reported in the art would have led one of skill to the regimen where a dose could be given 3 times per week as recited in the challenged claims.  The Board also considered PO’s secondary considerations but did not find them persuasive.  The Board stated that the unexpected results provided by PO were not compared to the closest prior art, and that when actually compared to the closest prior art, the results were not surprising.  With respect to commercial success, the Board further determined that PO was not considering the right criteria and was comparing market success of its product without accounting for the deep discounts provided to consumers on the new formulation, and that the PO did not demonstrate the required nexus between the market success and the claimed subject matter.  Finally, the Board stated that long-felt need was not demonstrated because there was no evidence that others had tried to come up with the claimed dosage and regimen and failed, citing the success of administration disclosed in Pinchasi.

These three related decisions remind the practitioner to carefully examine patentability arguments and ensure that the appropriate criteria and comparisons are provided to the Board, especially where secondary considerations of non-obviousness are argued.

While Teva will likely appeal these IPR decisions, Mylan still has a chance at striking down a fourth related patent in a pending district court action, thus paving the way for generic entry into the Copaxone market.