Gnosis Spa v. South Alabama Medical Science Foundation

1. Case Identification

• Case #: IPR2013-00116
• Patent #: Patent 5,997,915
• Filed: January 23, 2013
• Petitioner(s): Gnosis S.p.A., Gnosis Bioresearch S.A., and Gnosis U.S.A., Inc.
• Patent Owner(s): South Alabama Medical Science Foundation
• Challenged Claims: 37, 39, 40, 47, 66, 67, 73, 76, 78-81, 83, 84, 86-89, 91, 92, 94-97, 99, 100, 110, and 111

2. Patent Overview

• Title: Nutritional Compositions with Reduced Folate Isomers
• Brief Description: The ’915 patent relates to nutritional compositions and methods for increasing a human subject's dietary folate intake. The compositions comprise one or more natural isomers of reduced folate, such as 5-methyl-(6S)-tetrahydrofolic acid, in combination with an essential nutrient preparation containing a vitamin other than ascorbic acid.

3. Grounds for Unpatentability

Ground 1: Anticipation over Serfontein - All Challenged Claims are anticipated by Serfontein under 35 U.S.C. §102(b).

• Prior Art Relied Upon: Serfontein (European Patent EP 595,005).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Serfontein discloses every limitation of the challenged claims. Serfontein teaches dietary compositions for preventing or treating elevated homocysteine, comprising folate "or a suitable active metabolite of folate" combined with Vitamins B6 and B12. Petitioner contended a person of ordinary skill in the art (POSITA) would have understood the genus "suitable active metabolite of folate" to explicitly include the key species 5-methyl-tetrahydrofolic acid (5-MTHF) and 5-formyl-tetrahydrofolic acid (5-FTHF), particularly the biologically active 5-methyl-(6S)-tetrahydrofolic acid isomer. The compositions taught by Serfontein include vitamins other than ascorbic acid (Vitamins B6 and B12) at dosages meeting the claimed requirement of being greater than 25% of the daily requirement. Serfontein also discloses various administration methods (e.g., oral, daily, periodic) and patient populations (e.g., pregnant women, those with vascular disease) that map directly onto the limitations of the independent and dependent claims.

Ground 2: Obviousness over Czeizel and Folate-Substitution Art - All Challenged Claims are obvious over Czeizel in view of Scott, Leeming, or Barford, and further in view of Lucock or Marazza under 35 U.S.C. §103.

• Prior Art Relied Upon: Czeizel (a 1992 N. Engl. J. Med. article), Scott (a 1991 The Lancet article), Leeming (a 1991 The Lancet article), Barford (a 1981 British Medical Journal article), Lucock (a 1991 The Lancet article), and Marazza (Patent 5,194,611).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued Czeizel taught a multivitamin supplement containing folic acid for preventing neural tube defects. The combination of Scott, Leeming, and Barford explicitly taught the problem of unmetabolized folic acid in the plasma (a potential neurotoxin) and suggested using reduced folates, specifically 5-MTHF, as a safer and more natural alternative to folic acid for the same purpose.
  • Motivation to Combine: A POSITA would combine these teachings by substituting the 5-MTHF taught by Scott/Leeming/Barford for the folic acid in Czeizel's multivitamin composition. The motivation was clear and explicit: to achieve the same goal of folate supplementation while avoiding the known, harmful side effects of using folic acid. Further, Lucock and Marazza provided a motivation to use the substantially pure, natural 5-methyl-(6S)-tetrahydrofolic acid isomer over a racemic mixture, as the unnatural (6R) isomer was known to be inert and potentially interfere with folate transport.
  • Expectation of Success: A POSITA would have a high expectation of success, as the references were directed to the identical purpose of providing folate to prevent deficiencies and associated health issues, such as neural tube defects in pregnant women.

Ground 3: Obviousness over Serfontein and Dietary Supplement Art - All Challenged Claims are obvious over Serfontein in view of Marazza, Wood, or Ambrosini under §103.

• Prior Art Relied Upon: Serfontein (European Patent EP 595,005), Marazza (Patent 5,194,611), Wood (Patent 4,959,472), and Ambrosini (European Patent Application No. 627,435).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground starts with Serfontein's disclosure of a vitamin composition containing a "suitable active metabolite of folate." The secondary references—Marazza, Wood, and Ambrosini—all explicitly teach that 5-methyl-(6S)-tetrahydrofolic acid is a natural, chirally pure reduced folate that can and should be used as a "vitamin in folate deficiency states" or as a "dietary supplement."
  • Motivation to Combine: A POSITA would be motivated to select the specific, substantially pure 5-methyl-(6S)-tetrahydrofolic acid taught by Marazza, Wood, or Ambrosini to serve as the "suitable active metabolite of folate" in Serfontein's composition. This was not a novel combination but simply the selection of a preferred, well-known species (chirally pure 5-MTHF) for a disclosed genus (active folate metabolites) to use in a dietary supplement context, a use explicitly taught by the secondary references.
  • Expectation of Success: A POSITA would have a reasonable expectation of success because all references were directed to the same purpose of increasing dietary folate intake for health benefits.
• Additional Grounds: Petitioner asserted an additional obviousness challenge based on Serfontein in view of Godfrey or Regland, and further in view of Marazza, which relied on similar substitution theories but focused on the known use of 5-MTHF for treating homocysteine-associated psychiatric problems.

4. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 37, 39, 40, 47, 66, 67, 73, 76, 78-81, 83, 84, 86-89, 91, 92, 94-97, 99, 100, 110, and 111 of the ’915 patent as unpatentable.