PTAB

IPR2013-00012

Apotex Inc v. Alcon Pharmaceuticals Ltd

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1. Case Identification

2. Patent Overview

  • Title: Ophthalmic Antibiotic Compositions Containing Moxifloxacin
  • Brief Description: The ’830 patent discloses topical ophthalmic, otic, and nasal pharmaceutical compositions containing the fluoroquinolone antibiotic moxifloxacin. The patent is directed to using these compositions to treat bacterial infections in affected tissues.

3. Grounds for Unpatentability

Ground 1: Anticipation over Petersen - Claim 1 is anticipated by the ’942 patent under 35 U.S.C. §102.

  • Prior Art Relied Upon: Petersen (Patent 5,607,942).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the ’942 patent, titled and claiming antibacterial agents including moxifloxacin, expressly taught every limitation of claim 1. The ’942 patent disclosed moxifloxacin for treating eye infections, its formulation into ophthalmic compositions like eye ointments and drops for local therapy, and its combination with pharmaceutically suitable excipients. Critically, the ’942 patent disclosed a moxifloxacin concentration range of "about 0.1 to 99.5% by weight," which entirely subsumes the ’830 patent’s claimed range of 0.1 to 1.0 wt%. Petitioner asserted that the claimed range was not critical and offered no considerable difference from the prior art range, and therefore the disclosure of the broader range anticipated the narrower claimed range. The element of a "pharmaceutically acceptable vehicle" was argued to be inherently disclosed, as formulations like emulsions, ointments, or drops necessarily include such a vehicle.

Ground 2: Obviousness over Petersen and OCUFLOX® - Claim 1 is obvious over the ’942 patent in view of OCUFLOX® PDR.

  • Prior Art Relied Upon: Petersen (’942 patent) and OCUFLOX® PDR (a 1996 entry in the Physician's Desk Reference for Ofloxacin ophthalmic solution).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted the ’942 patent established that moxifloxacin was a known antibacterial compound suitable for ophthalmic formulations. The OCUFLOX® PDR provided a well-known, commercially available template for a topical ophthalmic solution, disclosing a 0.3% concentration of ofloxacin (a fluoroquinolone in the same class as moxifloxacin) in a pharmaceutically acceptable vehicle. A Person of Ordinary Skill in the Art (POSA) would look to the formulation of a successful, related compound like ofloxacin when developing a new ophthalmic product with moxifloxacin.
    • Motivation to Combine: A POSA would combine the teachings to create an alternative or improved therapy for bacterial eye infections. Knowing moxifloxacin's antibacterial properties from the ’942 patent, it would have been a simple and logical step to formulate it in a manner similar to the proven OCUFLOX® product. The 0.3% concentration of OCUFLOX® provided a clear starting point for formulating moxifloxacin within the claimed 0.1-1.0% range, requiring only routine optimization.
    • Expectation of Success: A POSA would have had a high expectation of success. The ’942 patent taught the suitability of moxifloxacin for ophthalmic use, and OCUFLOX® demonstrated a safe and effective vehicle for a closely related fluoroquinolone. Formulating topical ophthalmic solutions was a well-developed and predictable art at the time.

Ground 3: Obviousness over Dalhoff, OCUFLOX®, and Petersen Abstract - Claim 1 is obvious over Dalhoff in view of OCUFLOX® PDR and the Petersen Abstract.

  • Prior Art Relied Upon: Dalhoff (a 1996 article on the in vitro activity of moxifloxacin), OCUFLOX® PDR, and Petersen Abstract (a 1996 conference abstract on moxifloxacin).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground replaced the ’942 patent with Dalhoff as the primary reference for moxifloxacin's properties. Dalhoff taught that moxifloxacin was an excellent broad-spectrum antibiotic with antibacterial activity, particularly against gram-positive bacteria, that was 10-fold greater than ciprofloxacin. OCUFLOX® PDR again provided the template for a topical ophthalmic formulation. The Petersen Abstract was added to teach moxifloxacin’s high aqueous solubility (24 mg/ml), confirming its suitability for formulation in an aqueous vehicle at a high concentration.
    • Motivation to Combine: The motivation was to develop a superior ophthalmic antibiotic. Dalhoff’s disclosure of moxifloxacin’s enhanced potency, especially against bacteria resistant to other quinolones, would have strongly motivated a POSA to formulate it for topical use. A POSA would have combined this highly potent active ingredient with a known, safe, and effective formulation vehicle like that of OCUFLOX®. The Petersen Abstract’s disclosure of high solubility would have removed any doubt about the feasibility of creating such a formulation.
    • Expectation of Success: The combination of references created a strong expectation of success. Dalhoff established superior efficacy, OCUFLOX® provided a proven formulation strategy, and the Petersen Abstract confirmed the physical properties (high solubility) necessary for successful formulation. A POSA would reasonably expect that a highly potent and highly soluble drug could be successfully formulated into a safe and effective topical composition.

  • Additional Grounds: Petitioner asserted additional obviousness challenges against claim 1. These grounds relied on similar rationales but substituted CILOXAN® PDR (a reference for ciprofloxacin) for OCUFLOX® PDR or combined the ’942 patent with the Petersen Abstract to further support the expectation of success in formulating moxifloxacin.

  • Rebuttal of Patent Owner’s Anticipated Defenses: Across its obviousness grounds, Petitioner preemptively rebutted arguments that the art taught away from the invention. Petitioner argued that, contrary to Patent Owner’s likely assertions, fluoroquinolones were recognized as safe for topical ophthalmic use, and concerns over systemic toxicity were irrelevant to the small dosages used in topical treatments. Further, Petitioner argued that moxifloxacin’s high solubility would have led a POSA to expect it could be formulated at concentrations high enough to be effective against a wide range of bacteria, including P. aeruginosa. Petitioner also argued that secondary considerations of nonobviousness, such as unexpected results or long-felt need, were not met because the superior properties of moxifloxacin were not unexpected when compared to the closest prior art.

4. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claim 1 of Patent 6,716,830 as unpatentable.