PTAB

PGR2017-00039

KVK Tech Inc v. SilverGate Pharmaceuticals Inc

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1. Case Identification

2. Patent Overview

  • Title: LISINOPRIL FORMULATIONS
  • Brief Description: The ’183 patent is directed to stable oral liquid formulations of lisinopril, an ACE inhibitor used to treat hypertension. The claimed formulations comprise lisinopril, a sweetener (xylitol), a buffer system (citric acid/sodium citrate), a preservative (sodium benzoate), and water, maintained at a specific pH and exhibiting stability for at least 12 months.

3. Grounds for Unpatentability

Ground 1: Claims 1-13 are unpatentable for lack of enablement under 35 U.S.C. §112(a).

  • Core Argument for this Ground: Petitioner argued that the patent’s specification fails to enable a person of ordinary skill in the art (POSA) to practice the full scope of the claims, particularly the core limitation of stability for at least 12 months.
    • Prior Art Mapping: The patent defines stability based on the percentage of the “initial lisinopril amount” remaining after a storage period. However, the specification’s only working examples (Example F) did not directly measure the remaining lisinopril. Instead, they improperly measured only two known degradants, which is insufficient to determine the total lisinopril loss, as other degradation pathways exist.
    • Key Aspects: Petitioner contended that the stability data submitted during prosecution to overcome rejection (the Mosher Declaration) was post-filing date evidence and therefore cannot be used to cure the specification's lack of enablement. Furthermore, this new data was itself unreliable, showing a scientifically impossible increase in lisinopril concentration over time. The specification also lacked data for the longer stability periods recited in dependent claims (18 and 24 months).

Ground 2: Claims 1-13 are unpatentable for lack of adequate written description under 35 U.S.C. §112(a).

  • Core Argument for this Ground: Petitioner asserted that the written description requirement is not met for the same fundamental reasons as the enablement failure.
    • Prior Art Mapping: The argument is based on the fact that the application, as filed, contained no data demonstrating that the inventors were in possession of a formulation meeting the claimed stability profile. The lack of any working examples that actually measured stability as defined in the claims shows the inventors had not actually made or tested an embodiment of their invention by the filing date. Relying on post-filing evidence (the Mosher Declaration) confirms that possession of the claimed invention was not established at the time of filing.

Ground 3: Claims 1-13 are obvious over Beidel, Nerurkar, Pharma Compounding Sept. 2006, and Beidel Two under 35 U.S.C. §103.

  • Prior Art Relied Upon: Beidel (a 2011 AAPS meeting presentation), Nerurkar (WO 98/14196), Pharma Compounding Sept. 2006 (a journal article), and Beidel Two (a 2011 AAPS meeting abstract).
  • Core Argument for this Ground: Petitioner argued that the claimed formulation is an obvious combination of known elements for their predictable purposes, and the claimed stability is merely an inherent property of this obvious combination.
    • Prior Art Mapping:
      • Beidel taught a stable liquid lisinopril formulation at 1 mg/ml and a pH of ~4.8, demonstrating 92% stability after 210 days at 25°C. This established the basic formulation. However, Beidel required a flavoring agent, suggesting poor taste.
      • Nerurkar taught an oral liquid formulation for a different drug that used an excipient package nearly identical to that in the ’183 patent to solve similar problems. Specifically, Nerurkar disclosed using xylitol as a sweetener, a citric acid/sodium citrate buffer, and sodium benzoate as a preservative, all within a similar pH range.
      • A POSA would have looked to a reference like Nerurkar to improve Beidel's formulation. It would have been obvious to replace Beidel's acetate buffer with Nerurkar’s citrate buffer, as they have nearly identical pKa values (4.76) and are thus interchangeable for buffering at the target pH of ~4.8. It would also be obvious to use xylitol for sweetness and sodium benzoate for preservation, as these are standard, well-known excipients for these exact functions.
    • Motivation to Combine: A POSA was motivated to develop a palatable and stable oral liquid lisinopril formulation for patients who cannot swallow tablets. Beidel provided a starting point but had taste issues. Nerurkar provided a well-known path to improve palatability and ensure stability by disclosing a standard and compatible package of excipients (xylitol, citrate buffer, sodium benzoate) suitable for a liquid formulation.
    • Expectation of Success: A POSA would have had a high expectation of success. The combination involved substituting known ingredients for their established functions (e.g., a citrate buffer for an acetate buffer at the same pKa, xylitol for sweetness). The resulting stability was predictable, as a POSA knew to buffer a drug at its pH of maximum stability, and lisinopril’s stability peak (~pH 4.8) is very close to the pKa of the chosen citric acid buffer.

4. Key Technical Contentions (Beyond Claim Construction)

  • Stability is a Result, Not an Ingredient: Petitioner argued that stability is not a component of a formulation but a resulting property. Therefore, discovering a stability profile for an otherwise obvious combination of ingredients is not itself patentable. The prior art already taught all the formulation components and the reasons to combine them, making the resulting stability an inherent, unpatentable property.
  • Proper Stability Measurement: A central technical contention for the §112 grounds was that stability must be assessed by directly measuring the remaining active pharmaceutical ingredient (API), not by measuring a subset of its degradants. The patent owner's failure to provide such data in the specification was a fatal flaw.

5. Relief Requested

  • Petitioner requested institution of Post Grant Review and cancellation of claims 1-13 of the ’183 patent as unpatentable.