Mylan Laboratories Ltd. v. Aventis Pharma S.A.

IPR2016-00627
August 23, 2016

Brief Summary: Mylan’s Petition requesting IPR regarding claims 1 and 2 of Aventis’ US 5,847,170 encompassing the taxoid cabazitaxel (Jevtana®) denied.

Summary: Mylan filed a Petition requesting IPR of claims 1 and 2 of Aventis’ US 5,847,170 encompassing the taxoid cabazitaxel (Jevtana® for prostate cancer, especially Taxol® (paclitaxel)- or Taxotere® (docetaxel)-resistant cancers). Cabazitaxel includes a methoxy (OCH3) at the C-7 and C-10 positions and a carbonyl (C=O) at C-9, and the docetaxel side chain. Claim construction was found not to be necessary. The Decision explains that the prior art paclitaxel and docetaxel compounds do not include methoxy at C-7 or C-10 but do include carbonyl at C-9. Mylan alleged the “Kant” reference discloses paclitaxel analogues including one having C-7 hydroxyl, C-10 methoxy, and C-9 carbonyl and “reasonabl[y]…suggest[s] that the functional group at the C-10 position does modulate the anti-tumor activity, which is quite contrary to some of the earlier predictions.” Mylan also alleged that the “Klein” reference discloses compounds with “increased water solubility and stability as compared to taxol” (paclitaxel), including some with C-7 or C-9 methoxy and C-10 acetyl. Mylan acknowledged that “Kant does not describe the C-7 methoxy substitution” and “Klein does not disclose the C-10 methoxy” but “that a POSA would have selected Kant’s Compound 20 ‘for further modification’ (a so-called ‘lead compound’) because of its superior binding ability and cytotoxicity amound the chemical analogues having the docetaxel side chanin”. And it argued that modification would have been made “in view of Klein’s Table III (compounds 8 and 10) teaching increased anti-tumor potency by substituting a methoxy group for a hydroxyl group at C-7, which would have led to the synthesis of cabazitaxel.” The Board concluded, however, that there was insufficieny evidence the skilled artisan would have selected Kant’s Compound 20 as a lead compound (e.g., “Kant does not teach or suggest additional structural modifications to Compound 20 or docetaxel” and indicates the authors” were trying to “synthesize ‘novel paclitaxel analogues’”; Mylan “start[ed] with a hindsight-based structural comparison of docetaxel, Kant Compound 20, and cabazitaxel in side-by-side fashion”; and “Kant…does not teach or suggest the possibility of simultaneous substitution of both the C-7 and C-10 positions” but instead “focuses on the possibility of improving anti-tumor cytotoxicity of paclitaxel analogues by selective substitution and functionalization of only the C-10 position”). It was also not persuaded that the skilled artisan would have modified Kant Compound 20 in view of Klein because, e.g., “at least more significant decisions” would have been needed, “Klein expressly teaches the reduction of the C-9 carbonyl to a C-9 hydroxyl to increase aqueous stability and chemical stability”, “that a C-9 carbonyl was not required to maintain anti-tumor activity”, and “does not necessarily teach or suggest replacing the C-10 acetyl unless the C-9 carbonyl is reduced to a hydroxyl group” (“Petitioner’s analysis reflects improper hindsight”). The “Colin” reference was also cited by Mylan as disclosing docetaxel as a lead compound for ‘further optimization’” but the combination of Colin with Kant and Klein was not persusasive. Therefore, the Petition was denied.

This entry was posted in Generics / ANDA, Inter Parties Review (IPR), IPR, Obviousness. Bookmark the permalink.

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