Apotex Inc v. OSI Pharmaceuticals LLC

1. Case Identification

• Case #: IPR2016-01284
• Patent #: 6,900,221
• Filed: June 28, 2016
• Petitioner(s): Apotex Inc., Apotex Corp., Apotex Pharmaceuticals Holdings Inc., and Apotex Holdings, Inc.
• Patent Owner(s): OSI Pharmaceuticals, Inc.
• Challenged Claims: 44-47 and 53

2. Patent Overview

• Title: Stable Polymorph on N-(3-ethylphenyl)-6,7-bis(2methoxyethoxy)-4-quinazolinamine hydrochloride, Methods of Production, and Pharmaceutical uses thereof
• Brief Description: The ’221 patent discloses a stable crystalline form (polymorph B) of the compound erlotinib hydrochloride. While the patent focuses on this specific polymorph, the challenged claims are broader method-of-use claims directed to treating specific cancers with erlotinib, without limitation to any particular crystalline form.

3. Grounds for Unpatentability

Ground 1: Obviousness of Claims 44-46 and 53 over Schnur in view of Gibbs or OSI's 10-K

• Prior Art Relied Upon: Schnur (Patent 5,747,498), Gibbs (a Jan. 2000 journal article), and OSI's 10-K (a Dec. 1998 SEC filing).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the sole reason for allowance of the challenged claims during prosecution was that the primary prior art, Schnur, disclosed treating "lung cancer" generally but not non-small cell lung cancer (NSCLC) specifically. Schnur taught a method of treating hyperproliferative disorders, including lung cancer, by administering a therapeutically effective amount of erlotinib. Petitioner contended that two references not before the examiner, Gibbs and OSI's 10-K, explicitly bridge this gap. Gibbs disclosed that erlotinib demonstrated good anti-cancer activity "particularly in patients with NSCLC" and had entered Phase II clinical trials. Similarly, OSI's 10-K, a public filing from the Patent Owner's corporate predecessor, identified erlotinib as a treatment for NSCLC that had completed Phase I and initiated Phase II trials. These references supply the explicit NSCLC limitation of independent claim 44 and dependent claim 53.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) reviewing Schnur's disclosure of erlotinib for treating lung cancer would have been aware of contemporaneous publications like Gibbs and OSI's 10-K. These references specified that NSCLC was a primary indication for erlotinib, the very compound identified as preferred in Schnur. A POSITA would combine these teachings because they concern the exact same compound (erlotinib), the same therapeutic field (oncology), and the same mechanism of action (EGFR inhibition), with the secondary references merely providing greater specificity on the type of lung cancer being targeted in then-current clinical trials.
  • Expectation of Success: A POSITA would have had a high expectation of success. Schnur established the utility of erlotinib for lung cancer, and Gibbs and OSI's 10-K confirmed that the compound was already in Phase II human clinical trials specifically for treating NSCLC. This demonstrated to the public that the compound was considered promising and safe enough for advanced human testing for this exact indication.

Ground 2: Obviousness of Claim 47 over Schnur in view of Gibbs or Wakeling, and further in view of Moscatello

• Prior Art Relied Upon: Schnur (Patent 5,747,498), Gibbs (a Jan. 2000 journal article), Wakeling (a 1996 journal article), and Moscatello (a Jan. 1998 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Claim 47 depends from claim 44 and adds the limitation that the treatment is for "tumors that express EGFRvIII." Petitioner asserted that Schnur, Gibbs, and Wakeling all established that erlotinib is a 4-anilinoquinazoline compound that functions by inhibiting the epidermal growth factor receptor (EGFR). The Moscatello reference taught that the common mutant variant, EGFRvIII, found in NSCLC tumors, is also inhibited by this same class of compounds. Moscatello demonstrated that another 4-anilinoquinazoline (tyrphostin AG1478), which is structurally similar to erlotinib, was effective at inhibiting both normal EGFR and the EGFRvIII variant.
  • Motivation to Combine: A POSITA seeking to treat cancers involving EGFR, as taught by Schnur, would have been motivated to consult research like Moscatello to understand the compound's effect on known EGFR mutations. Because Moscatello showed that the EGFRvIII variant was susceptible to inhibition by a structurally similar compound, a POSITA would have been motivated to apply erlotinib, a known potent EGFR inhibitor, to treat tumors expressing this variant. The references all address the same problem—inhibiting EGFR signaling to treat cancer—and provide complementary information about the target and the therapeutic agents.
  • Expectation of Success: A POSITA would have reasonably expected erlotinib to inhibit EGFRvIII. Both erlotinib and the compound tested in Moscatello belong to the same well-defined class of 4-anilinoquinazoline EGFR inhibitors and share a core chemical structure and mechanism of action. Given this functional and structural similarity, it would have been predictable that erlotinib would be effective against the same EGFRvIII target.
• Additional Grounds: Petitioner asserted an alternative ground that, if the challenged claims are accorded an earlier priority date, they would be anticipated by Schnur under 35 U.S.C. §102.

4. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 44-47 and 53 of the ’221 patent as unpatentable.