Novartis Pharmaceuticals Corp v. Regents Of University Of Michigan

1. Case Identification

• Case #: IPR2023-01347
• Patent #: 10,633,344
• Filed: August 28, 2023
• Petitioner(s): Novartis Pharmaceuticals Corporation
• Patent Owner(s): Regents of the University of Michigan and University of South Florida
• Challenged Claims: 16

2. Patent Overview

• Title: Multiple-Component Solid Phases Containing At Least One Active Pharmaceutical Ingredient
• Brief Description: The ’344 patent relates to pharmaceutical compositions containing a specific type of co-crystal. The claimed composition includes a therapeutically effective amount of a co-crystal solvate, which is comprised of an active pharmaceutical ingredient (API), a co-former, and a solvent molecule that non-covalently links repeating structural units.

3. Key Technical Contentions (Beyond Claim Construction)

• Contested Priority Date: A central argument of the petition is that claim 16 is not entitled to its claimed priority dates of March 1, 2002, and March 3, 2003. Petitioner asserted the correct priority date is the application's filing date of February 13, 2014, because the priority applications allegedly fail to meet the written description and enablement requirements of 35 U.S.C. §112 for the full scope of claim 16. This assertion is foundational to the obviousness grounds, which rely on prior art published after 2003 but before 2014.
• Lack of Written Description: Petitioner argued the priority applications are devoid of written description support for the claimed genus of co-crystal solvates. It contended that none of the examples in the priority applications describe a co-crystal that satisfies all limitations of claim 16, particularly the requirement that a solvent molecule non-covalently bonds supramolecular synthons to one another. Petitioner asserted that the few examples involving a solvent either fail other limitations or describe solvent molecules that are merely trapped within crystal channels rather than linking synthons as required.
• Lack of Enablement: Petitioner argued that, as of 2002-2003, the fields of co-crystal and solvate formation were highly unpredictable. It contended that practicing the full, broad scope of claim 16—covering a vast genus of APIs, co-formers, and solvents—would have required undue experimentation. The petition highlighted the lack of working examples or guidance in the priority applications on how to reliably create the specifically claimed solvated co-crystal structures. Furthermore, Petitioner argued that embodiments where the API's functionality is a "carbonyl" are inoperative because a carbonyl group lacks a hydrogen bond donor and thus cannot form the "API homosynthons" required by the claims, rendering a portion of the claim scope non-enabled.

4. Grounds for Unpatentability

Ground 1: Obviousness over Furosemide Co-Crystal Art - Claim 16 is obvious over Ueto in view of Li, Martindale, the ’006 Publication, and Remington.

• Prior Art Relied Upon: Ueto (a 2012 journal article), Li (a 2011 journal article), Martindale (a drug reference book), the ’006 Publication (Application # 2003/0224006), and Remington (a 2012 textbook).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that Ueto disclosed a 1:1:2 furosemide/nicotinamide/water co-crystal that meets all structural limitations of claim 16. Specifically, Ueto’s co-crystal is a solvate where water molecules non-covalently link supramolecular synthons formed between furosemide (the co-former) and nicotinamide (the API). Li was cited to expressly teach that nicotinamide, in its pure form, forms API homosynthons via hydrogen bonding between its carboxamide groups, meeting another key limitation. Martindale was used to establish that furosemide is a solid at room temperature and to provide therapeutic dosage information for both components.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine these references to develop a drug product with improved characteristics. Petitioner argued a POSITA would be motivated to form a co-crystal of furosemide, a drug known for low water solubility, to improve its physicochemical properties. Once the Ueto co-crystal was known, a POSITA would consult standard references like Martindale for dosing and Remington and the ’006 Publication for well-known methods of formulating the co-crystal into a pharmaceutical composition with an acceptable carrier.
  • Expectation of Success: Petitioner contended a POSITA would have a reasonable expectation of success in formulating the Ueto co-crystal into a final pharmaceutical composition using conventional and predictable formulation techniques described in Remington.

Ground 2: Obviousness over Genistein Co-Crystal Art - Claim 16 is obvious over the ’408 application and/or Sowa in view of Marini, Li, the ’006 Publication, and Remington.

• Prior Art Relied Upon: The ’408 application (a 2013 Polish patent application publication), Sowa (a 2013 journal article), Marini (a 2007 journal article), Li, the ’006 Publication, and Remington.
• Core Argument for this Ground:
  • Prior Art Mapping: This ground presented an alternative co-crystal combination. Petitioner argued the ’408 application and Sowa both disclosed a 1:1:1 genistein/nicotinamide/water co-crystal solvate that meets the claim’s structural requirements. In this combination, genistein acted as the co-former and nicotinamide as the API, with water linking the supramolecular synthons. Li was again cited for the teaching that nicotinamide forms the required API homosynthons. Marini was used to show the therapeutic use of genistein (for treating bone loss) and establish an effective dose, while Sowa disclosed that genistein is a solid at room temperature.
  • Motivation to Combine: A POSITA would be motivated to improve the known low solubility and bioavailability of genistein by forming a co-crystal. Upon discovering the genistein/nicotinamide co-crystal in Sowa or the ’408 application, a POSITA would be motivated to formulate it for its known therapeutic purpose (e.g., reducing bone loss) by consulting Marini for dosage information and Remington and the ’006 Publication for standard formulation techniques.
  • Expectation of Success: Petitioner argued that formulating the described co-crystal into a therapeutically effective composition was a routine and predictable task for a POSITA.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §314(a) and the Fintiv factors would be inappropriate. It provided a stipulation that, if the IPR is instituted, it will not pursue in parallel district court litigation the same grounds or any other grounds that could have reasonably been raised in the petition. Petitioner also asserted that the parallel litigation is at an early stage with no trial date set.
• Petitioner further argued against denial under §325(d), contending that the arguments and primary prior art references (Ueto, Sowa, and the ’408 application) are not cumulative to art considered during prosecution, as none were before the examiner.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claim 16 of Patent 10,633,344 as unpatentable.