PTAB

IPR2019-00345

Maia Pharmaceuticals, Inc. v. Bracco Diagnostics Inc.

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1. Case Identification

2. Patent Overview

  • Title: Stabilized Sincalide Formulations and Methods of Making Same
  • Brief Description: The ’046 patent describes stabilized, physiologically acceptable parenteral formulations of sincalide, a peptide drug. The claims recite formulations containing sincalide combined with a set of standard functional excipients, including a stabilizer, a surfactant/solubilizer, a chelator, a bulking agent, and a buffer, as well as methods of making and using these formulations for medical imaging.

3. Grounds for Unpatentability

Ground 1: Obviousness over PDR and Sato - Claims 1-4, 6-11, 13, 15, 16, 19, 21-24, 26-31, 33, 35, 36, 40-42, 44-49, 51, 53, 55, and 104 are obvious over PDR in combination with Sato.

  • Prior Art Relied Upon: PDR (Physicians' Desk Reference For Radiology and Nuclear Medicine, 1977/78) and Sato (WO 00/5169).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the Physicians' Desk Reference (PDR) disclosed the original, unstable Kinevac formulation, which contained sincalide and a simple bulking agent (sodium chloride). This reference established the base product and its well-known problems of chemical and physical instability (hydrolysis, oxidation, and surface adsorption). Sato taught methods for creating stable lyophilized formulations of unstable peptides, including cholecystokinin (the family to which sincalide belongs). Sato disclosed using the exact functional classes of excipients recited in independent claim 1 of the ’046 patent to solve the very same instability problems. Specifically, Sato taught adding stabilizers (e.g., amino acids like methionine and antioxidants) to prevent oxidation, surfactants (e.g., polysorbates) to prevent surface adsorption, chelators (e.g., EDTA) to complex trace metals that catalyze oxidation, bulking agents (e.g., mannitol) for lyophilized products, and buffers (e.g., phosphate) to maintain optimal pH.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA), aware of the known stability issues of the sincalide formulation in the PDR, would be motivated to improve it. Sato provided an explicit roadmap for stabilizing unstable peptides like sincalide by combining them with a standard set of functional excipients. Because Sato expressly stated its teachings were applicable to cholecystokinin, a POSITA would combine the teachings of PDR and Sato to arrive at the claimed stabilized formulation.
    • Expectation of Success: Sato provided extensive experimental data demonstrating that its combination of excipients successfully stabilized other unstable peptides, such as G-CSF, by preventing degradation and improving recovery after long-term storage. This success with analogous peptides would have given a POSITA a reasonable expectation that applying the same principles and excipient classes to sincalide would predictably yield a stable formulation.

Ground 2: Obviousness over PDR, Sato, and Nema - Claims 5, 12, 14, 17, 18, 25, 32, 34, 37, 38, 43, 50, 52, and 54 are obvious over PDR in combination with Sato and Nema.

  • Prior Art Relied Upon: PDR, Sato, and Nema (Nema et al., “Excipients and Their Use in Injectable Products,” 1997).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground builds on Ground 1 by adding Nema to address dependent claims that recite specific chemical compounds for the functional excipient classes. While Sato taught the broad functional classes, Nema provided a list of common, FDA-approved excipients for parenteral use. For example, to meet the limitation of dibasic potassium phosphate (claim 5), Petitioner pointed to Nema’s disclosure of "Potassium phosphate, dibasic" as a standard buffer. To meet the limitation of sodium metabisulfite (claim 12), Petitioner cited Nema’s disclosure of it as a frequently used antioxidant. The argument was that selecting a specific, well-known, and safe compound from a list of known options for a taught functional category represented a simple and obvious design choice.
    • Motivation to Combine: A POSITA, having decided to use the functional excipients taught by Sato, would be motivated to consult a reference like Nema to select a specific, proven, and safe compound for each role. This would be a routine step in the formulation development process.

Ground 3: Obviousness over PDR, Sato, and ENMS - Claims 77-88, 90-95, 97, 99, 100, and 105 are obvious over PDR, Sato, and ENMS.

  • Prior Art Relied Upon: PDR, Sato, and ENMS (Essentials of Nuclear Medicine Science, 1987).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground targets the method of imaging claims (e.g., claim 77) by adding ENMS to the base combination. While PDR and Sato taught the stabilized sincalide formulation, ENMS taught the standard clinical protocol for using it. ENMS disclosed administering a hepatobiliary imaging agent (e.g., 99mTc-IDA) to a patient in conjunction with sincalide. It further taught administering sincalide either before or after the imaging agent and detecting the agent with a device like a gamma camera to image the gallbladder. This combination of references disclosed all steps of the claimed imaging methods.
    • Motivation to Combine: A POSITA would be motivated to use the improved, stabilized sincalide formulation (from PDR and Sato) in the known and established diagnostic imaging procedure described in ENMS. This amounted to the obvious application of an improved composition in a conventional process.

  • Additional Grounds: Petitioner asserted a fourth ground of obviousness against claims 89, 96, 98, 101, and 102 over the combination of PDR, Sato, ENMS, and Nema. This ground applied the rationale from Ground 2 (using Nema to select specific excipients) to the imaging method claims established in Ground 3.

4. Relief Requested

  • Petitioner requests the institution of an inter partes review and the cancellation of claims 1-19, 21-38, 40-55, 77-102, and 104-105 of Patent 6,803,046 as unpatentable under 35 U.S.C. §103.