Prollenium US Inc v. Allergan Industrie SAS

1. Case Identification

• Case #: IPR2019-01508
• Patent #: 9,238,013
• Filed: August 23, 2019
• Petitioner(s): Prollenium US Inc.
• Patent Owner(s): Allergan Industrie, SAS
• Challenged Claims: 1-4

2. Patent Overview

• Title: Hyaluronic Acid-Based Gels Including Lidocaine
• Brief Description: The ’013 patent discloses injectable dermal filler compositions comprising hyaluronic acid (HA) crosslinked with 1,4-butanediol diglycidyl ether (BDDE), free HA, and the anesthetic lidocaine, which are heat sterilized and stable.

3. Grounds for Unpatentability

Ground 1: Claims 1-4 are obvious over Lebreton in view of Sadozai and Monheit.

• Prior Art Relied Upon: Lebreton (Application # 2006/0194758), Sadozai (Application # 2005/0136122), and Monheit (a Feb. 2007 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Lebreton, by the same inventor as the challenged patent, disclosed all features of the claims except for the inclusion of 0.3% lidocaine and free HA. Lebreton taught a BDDE-crosslinked HA dermal filler with a pH of about 7.2 that was heat sterilized in an autoclave. Sadozai taught adding 0.3% lidocaine to a different (BDCI-crosslinked) HA filler, which was then heat sterilized and found to be stable, even suggesting lidocaine increased stability. Monheit taught the conventional practice of adding free HA to crosslinked HA compositions as a lubricant to improve flow characteristics. The claimed extrusion force and viscosity ranges in dependent claims 2 and 3 were argued to be typical, inherent, or achievable through routine optimization. Claim 4’s stability requirement was argued to be an inherent result of sterilizing an otherwise obvious composition in a sealed container.
  • Motivation to Combine: A POSITA would combine Lebreton’s BDDE-crosslinked filler with lidocaine as taught by Sadozai to solve the well-known problem of injection pain. By the patent's priority date, lidocaine had already been successfully incorporated into heat-sterilized HA fillers using the three other primary crosslinkers (DVS, BDCI, and DEO), making its application to the fourth (BDDE) a predictable next step. A POSITA would also add free HA per Monheit to optimize the filler’s injection properties, a routine practice.
  • Expectation of Success: A POSITA would have a high expectation of success because lidocaine had been repeatedly and successfully used in other crosslinked HA fillers without causing degradation. Sadozai explicitly taught that adding lidocaine to a heat-sterilized HA filler did not decrease, and could even increase, stability.

Ground 2: Claims 1-4 are obvious over Kinney, Zhao, and Narins.

• Prior Art Relied Upon: Kinney (a Nov./Dec. 2006 journal article), Zhao (Application # 2005/0250939), and Narins (an Apr. 2005 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Kinney described two dermal fillers: Restylane (a single-BDDE crosslinked HA with free HA, which was effective but painful) and Puragen Plus (a double-DEO crosslinked HA with 0.3% lidocaine, which provided a relatively pain-free injection). Zhao taught methods for preparing double-crosslinked HA and disclosed that BDDE and DEO were interchangeable bis-epoxide crosslinkers. Narins provided additional details on Restylane, confirming it was heat sterilized and had a long shelf life.
  • Motivation to Combine: A POSITA would be motivated to improve the well-established, FDA-approved BDDE-based Restylane filler by making it less painful. Knowing from Kinney that adding lidocaine to a DEO-crosslinked filler (Puragen Plus) reduced pain, and from Zhao that DEO and BDDE crosslinkers were interchangeable, a POSITA would be motivated to substitute the DEO in Puragen Plus with the market-preferred BDDE. This would create a pain-reduced, BDDE-based filler, combining the benefits of both products described by Kinney.
  • Expectation of Success: Given the chemical similarity between BDDE and DEO as bis-epoxide crosslinkers, a POSITA would reasonably expect that a process for making a DEO-crosslinked filler could be adapted for BDDE. A POSITA would also expect lidocaine to function analogously in both gel types without issue.

Ground 3: Claims 1-4 are obvious over Reinmuller in view of Lebreton and Monheit.

• Prior Art Relied Upon: Reinmuller (Patent 5,731,298), Lebreton (Application # 2006/0194758), and Monheit (a Feb. 2007 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued Reinmuller disclosed a heat-sterilized, DVS-crosslinked HA composition containing lidocaine to mitigate injection pain. Lebreton taught that BDDE-crosslinked HA fillers were superior to other types, exhibiting longer in vivo residence times. Monheit taught adding free HA to improve flow characteristics.
  • Motivation to Combine: A POSITA would be motivated to improve the composition in Reinmuller by replacing the DVS crosslinker with the superior BDDE crosslinker taught by Lebreton. This modification constituted a simple substitution of one conventional crosslinker for another to gain the known advantages of BDDE-based fillers, such as market acceptance and increased durability. Adding free HA per Monheit would be a routine optimization.
  • Expectation of Success: A POSITA would have a reasonable expectation that substituting one well-known HA crosslinker for another would successfully result in a lidocaine-containing dermal filler. The function of lidocaine in reducing pain was independent of the specific crosslinker used.

4. Key Claim Construction Positions

• "Heat sterile" (claim 1): Petitioner argued this term is a product-by-process feature. For validity analysis, the process recitation ("obtained by subjecting the composition to heat") should be ignored, and the claim should cover any sterile filler meeting the other limitations, regardless of the sterilization method.
• "Stable" (claim 4): Petitioner proposed that "stable" be construed to mean the composition maintains at least one of several aspects, including transparent appearance, pH, extrusion force, rheological characteristics, or HA concentration.

5. Key Technical Contentions (Beyond Claim Construction)

• Refutation of "Unexpected Results": Petitioner’s central technical contention was that the patent was granted based on the Patent Owner’s erroneous argument of "unexpected results." During prosecution, the inventor submitted a declaration stating a POSITA would have believed that adding lidocaine to HA gels would cause degradation during heat sterilization. Petitioner argued this was unsubstantiated and directly contradicted by the state of the art, where multiple FDA-approved, heat-sterilized HA fillers containing lidocaine (using DVS, BDCI, and DEO crosslinkers) already existed.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) was inappropriate because the Examiner erred in allowing the claims. The error stemmed from relying on the applicant's unsubstantiated declaration of "unexpected results" and having an incomplete picture of the prior art. Petitioner contended that it presented new prior art not before the Examiner (e.g., Zhao, Monheit) and demonstrated that the Examiner failed to appreciate the full weight of references that were cited (e.g., Sadozai), which explicitly taught the stability of lidocaine-containing HA fillers.

7. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-4 of the ’013 patent as unpatentable.