Cipla Ltd v. Alcon Research Ltd

1. Case Identification

• Case #: IPR2018-01020
• Patent #: 8,791,154
• Filed: June 5, 2018
• Petitioner(s): Cipla Limited
• Patent Owner(s): Alcon Research, Ltd.
• Challenged Claims: 1-27

2. Patent Overview

• Title: High Concentration Olopatadine Ophthalmic Composition
• Brief Description: The ’154 patent discloses aqueous ophthalmic solutions for treating ocular allergic conjunctivitis. The compositions comprise a high concentration of olopatadine (at least 0.67% w/v) stabilized with a combination of excipients including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropyl-γ-cyclodextrin (HP-γ-CD).

3. Grounds for Unpatentability

Ground 1: Claims 1-27 are obvious over Bhowmick, Yanni, and Castillo

• Prior Art Relied Upon: Bhowmick (WO 2008/015695), Yanni (a 1996 journal article), and Castillo (Patent 6,995,186).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the combination of these references taught every element of the challenged claims. Bhowmick taught stable ophthalmic solutions of olopatadine, addressing known precipitation issues by using cyclodextrins, and specifically identified HP-γ-CD as a "suitable" option for this purpose. While Bhowmick’s examples used lower olopatadine concentrations, Yanni taught that olopatadine efficacy increases with concentration up to 1 w/v %, providing a clear reason to increase the concentration to the claimed level of at least 0.67 w/v %. To solve the resulting stability issues at higher concentrations, Castillo taught that adding known stabilizers like PEG 400 (which has a molecular weight within the claimed range) and PVP enhances the stability of olopatadine solutions. Bhowmick and Castillo both taught the use of benzalkonium chloride as a standard preservative.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) seeking to create a more effective, longer-lasting olopatadine formulation would be motivated by Yanni to increase the drug concentration beyond what was shown in Bhowmick. To manage the well-known stability problems of olopatadine, a POSA would look to established techniques. Castillo provided a known solution by teaching the use of PEG and PVP to enhance olopatadine stability. A POSA would combine these complementary teachings to create a stable, high-concentration formulation, which was a simple and predictable path.
  • Expectation of Success: A POSA would have a reasonable expectation of success because all components—olopatadine, cyclodextrins, PEG, and PVP—were well-known excipients in ophthalmic formulations used for their predictable solubilizing and stabilizing properties. Combining them would represent routine optimization, not invention.

Ground 2: Claims 1-27 are obvious over Schneider, Hayakawa, Bhowmick, and Castillo

• Prior Art Relied Upon: Schneider (Application # 2011/0082145), Hayakawa (Patent 5,641,805), Bhowmick (WO 2008/015695), and Castillo (Patent 6,995,186).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Schneider, as the primary reference, taught olopatadine solutions for allergic conjunctivitis at concentrations of "0.60% w/v, or higher," directly suggesting the claimed concentration range. Schneider also expressly taught it is desirable to include other compounds to enhance solubility, listing PEG and PVP as suitable optional polymers. Hayakawa provided further motivation by teaching that olopatadine is effective in concentrations as high as 5 w/v %. For the remaining limitations, Bhowmick taught the specific use of HP-γ-CD to solubilize olopatadine, and Castillo provided explicit examples of using PEG 400 and PVP to stabilize olopatadine formulations.
  • Motivation to Combine: A POSA starting with Schneider's teaching of a 0.60% "or higher" olopatadine solution would be motivated by Hayakawa to pursue even higher concentrations for improved therapeutic benefit. To achieve the necessary stability for such a formulation, the POSA would be guided by Schneider's own suggestion to add solubilizers. The POSA would then naturally look to references like Bhowmick and Castillo, which provide specific, successful examples of using cyclodextrins (Bhowmick) and PEG/PVP (Castillo) to stabilize the exact active ingredient at issue.
  • Expectation of Success: A POSA would reasonably expect success, as the proposed combination involves using known excipients for their established purposes in a predictable art. The combination represents a predictable assembly of known elements to achieve a desired, foreseeable result.

4. Key Claim Construction Positions

• Petitioner argued that its invalidity case prevails even under the District Court's construction of "at least 0.67 w/v % olopatadine," which it interpreted as containing an upper limit of 1.0 w/v %. Petitioner contended that its evidence and prior art combinations teach the claimed invention even within this potentially narrower range, asserting that a dispute over the precise construction was unnecessary for a finding of unpatentability.

5. Key Technical Contentions (Beyond Claim Construction)

• Priority Date Challenge: Petitioner contended that the ’154 patent is not entitled to the priority date of its earliest provisional application (the ’789 Provisional). The argument centered on a lack of written description under 35 U.S.C. §112, as the ’789 Provisional allegedly only disclosed β-cyclodextrin derivatives and completely failed to mention the claimed hydroxypropyl-γ-cyclodextrin. Therefore, Petitioner argued the patent's effective priority date should be the filing date of a later provisional, which would make certain prior art references available for the obviousness analysis.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that the Patent Trial and Appeal Board (PTAB) should not exercise discretionary denial under 35 U.S.C. §325(d) or §314(a) based on a prior District Court decision that found certain claims of the patent not invalid. The asserted reasons were that the current inter partes review (IPR) presents different grounds and prior art combinations than those litigated in court. Petitioner also contended that the District Court erred by focusing too heavily on the "preferred embodiments" of the prior art and on the existence of commercial "gold standard" products, rather than considering the full scope of what the prior art teaches a POSA.

7. Relief Requested

• Petitioner requests institution of an IPR and cancellation of claims 1-27 of Patent 8,791,154 as unpatentable.