PTAB Institutes Inter Partes Review of Oracea (doxycycline) Formulation Patents


The U.S. Patent Trial and Appeal Board issued a trio of related decisions on December 17, 2013, each instituting inter partes review of one of three related patents on once-daily formulations of tetracycline.

On June 20, 2013, Amneal Pharmaceuticals filed three petitions for inter partesreview, seeking to invalidate a family of patents owned by Supernus Pharmaceuticals.  Each of the challenged patents–U.S. Patent Nos. 8,206,740;8,394,405; and 8,394,406–relates to once-daily, sub-antimicrobial formulations of doxycycline used to inhibit collagen destruction enzymes without provoking undesired side effects attendant to an antibacterial dose.

Claim 1 of the ‘740 patent is illustrative of the claimed subject matter:

1. An oral pharmaceutical composition of doxycycline, which at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of 0.1 μg/ml and a maximum of 1.0 μg/ml, the composition consisting of

(i) an immediate release (IR) portion comprising 30 mg doxycycline;

(ii) a delayed release (DR) portion comprising 10 mg doxycycline; and optionally,

(iii) one or more pharmaceutically acceptable excipients.

Amneal asserted the same four grounds of unpatentability in each petition, but the Board accepted only two.  Amneal first asserted that the challenged claims were unpatentable for obviousness over WO 02/080932 A1 (“Ashley ‘932”) as it incorporates Ser. No. 60/281,854 (“Ashley ‘854”).  Amneal also asserted that the challenged claims were unpatentable for obviousness over Ashley ‘932 as it incorporates Ashley ‘854 in combination with U.S. 5,348,748 (“Sheth”).  According to the petitions, Ashley ‘932 discloses administering a tetracycline compound in sub-antibacterial doses to treat acne, and further cites and incorporates Ashley ‘894 for disclosure of administering by sustained release, while Sheth discloses a once-daily formulation of minocycline with varying proportions of quick-release and delayed release dosage forms.

In each decision (-00368-00371-00372), the Board determined that Amneal had failed to demonstrate a reasonable likelihood of unpatentability for obviousness over Ashley ‘932 alone.  The Board rejected Amneal’s argument that a person of ordinary skill would have envisaged the claimed ratios of immediate-release to delayed-release portions from the disclosure in Ashley ‘854 that at least half of the doxycycline dose be released in the upper GI tract.

The Board was more receptive to Amneal’s second proffered ground of unpatentability; namely, that the subject matter of the challenged claims is obvious over the combination of Ashley ‘932 and Sheth.  Specifically, Amneal argued that Ashley ‘932 discloses all limitations of the illustrative claims except for the particular ratios of immediate-release and delayed-release portions of the formulation.  Rejecting Supernus’s counterarguments, the Board agreed that Sheth disclosed formulations of minocycline having a range of immediate-release to delayed-release ratios from which a person of ordinary skill could have envisaged the claimed ratios.

In the end, the Board instituted inter partes review of each of the three challenged patents, finding that Amneal had demonstrated a reasonable likelihood that the challenged claims in each patent were unpatentable over the combination of Ashley ‘932 and Sheth.

The petitions are related to ongoing litigation between the parties (currently stayed by joint stipulation), in which Galderma and Supernus alleged infringement of the ‘740 patent (the parent of the ‘405 and ‘406 patents) by Amneal’s ANDA No. 203-278 and proposed generic version of Oracea.  See Galderma Labs. Inc., et al. v. Amneal Pharms., LLC, et al., C.A. No. 11-1106-LPS (D. Del.).

Originally published on Orange Book Blog.

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