PTAB

IPR2013-00116

GnOSIs Spa v. South ALabama Medical Science FoundatION

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1. Case Identification

2. Patent Overview

  • Title: Nutritional Compositions Comprising Natural Isomers of Reduced Folate
  • Brief Description: The ’915 patent is directed to nutritional compositions, including vitamin preparations, comprising specific "natural isomers of reduced folate." The patent also claims methods of increasing a human subject's dietary intake of folate by administering such compositions, particularly in combination with other vitamins.

3. Grounds for Unpatentability

Ground 1: Anticipation by Serfontein - All challenged claims are anticipated under 35 U.S.C. §102 by Serfontein.

  • Prior Art Relied Upon: Serfontein (European Patent Application No. 0595005A11).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Serfontein discloses every limitation of the challenged claims. Serfontein teaches compositions for preventing or treating elevated homocysteine that are suitable for use as "dietary preparations." These compositions comprise Vitamin B6, Vitamin B12, and "folate or a suitable active metabolite of folate." Petitioner contended that the genus "suitable active metabolite of folate" was small and well-defined at the time, consisting primarily of 5-methyl-tetrahydrofolic acid (5-MTHF) and 5-formyl-tetrahydrofolic acid (5-FTHF). Citing legal precedent, Petitioner asserted that disclosure of such a limited, closely related genus explicitly identifies each member, thereby disclosing the 5-methyl-(6S)-tetrahydrofolic acid recited in the ’915 patent claims. Furthermore, Serfontein discloses its compositions contain vitamins (B6 and B12) other than ascorbic acid in amounts (e.g., 5 mg of vitamin B6) that are greater than the 25% of the daily requirement threshold specified in claim 37.

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

  • 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: Czeizel disclosed the use of a multivitamin supplement containing folic acid for women to prevent neural tube defects. The combination of Scott, Leeming, and Barford explicitly suggested that using a reduced folate, specifically 5-MTHF, is preferable to using folic acid for this purpose. Their reasoning was to avoid exposing the mother and fetus to unmetabolized folic acid, which was considered a potential neurotoxin. This combination taught the core of the claimed invention: a vitamin preparation for increasing folate intake using a reduced folate instead of standard folic acid. The further combination with Lucock or Marazza taught the final step: using the substantially pure, natural (6S) isomer of 5-MTHF. Marazza disclosed that the unnatural (6R) isomer was believed to be inert and could potentially interfere with the folate transport system, making the natural isomer the clear choice for efficacy.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine Czeizel with Scott et al. to solve the known and documented problem of unmetabolized folic acid accumulation and its potential "damaging effects." A POSITA would be further motivated to incorporate the teachings of Lucock or Marazza to purify the active (6S) isomer from any racemic mixture of 5-MTHF. This would be a simple purification of a known active ingredient to remove an inert or potentially harmful isomer, a routine step to increase the safety and efficacy of the final composition.
    • Expectation of Success: A POSITA would have had a high expectation of success, as all cited references are directed to the same purpose of providing safe and effective folate supplementation to females to prevent birth defects.

Ground 3: Obviousness over Serfontein and Dietary Supplement Art - All challenged claims are obvious over Serfontein in view of Marazza, Wood, or Ambrosini.

  • Prior Art Relied Upon: Serfontein (European Patent Application No. 0595005A11), 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 was presented to counter arguments made by the Patent Owner during a prior reexamination, where it was asserted that reduced folates were only known for "clinical" or "drug" uses, not as dietary supplements. Serfontein taught a dietary preparation containing a general "suitable active metabolite of folate." Marazza, Wood, and Ambrosini explicitly disclosed that the specific, chirally pure, natural isomer, 5-methyl-(6S)-tetrahydrofolic acid, was suitable for use as a "dietary supplement" (Wood) and as a "vitamin in folate deficiency states" (Marazza). These references directly teach the use of the claimed compound for the claimed purpose of nutritional supplementation.
    • Motivation to Combine: A POSITA looking to implement Serfontein's dietary preparation would have been motivated to select a specific compound for Serfontein’s generally disclosed "active metabolite of folate." The teachings of Marazza, Wood, and Ambrosini would have directed the POSITA to use 5-methyl-(6S)-tetrahydrofolic acid, as these references explicitly identified it as a safe and effective option for dietary and vitamin supplementation, directly contradicting the notion that it was only for limited clinical use.
    • Expectation of Success: The expectation of success would have been high. The secondary references (Marazza, Wood, Ambrosini) expressly confirm the suitability of the specific reduced folate isomer for the exact purpose disclosed in the primary reference (Serfontein), which is increasing dietary intake of folate.

  • Additional Grounds: Petitioner asserted an additional obviousness challenge over Serfontein in view of Godfrey or Regland and in further view of Marazza. This ground argued that Serfontein's disclosure of treating "homocysteine-associated psychiatric problems" would have motivated a POSITA to use 5-MTHF as taught by Godfrey and Regland for that specific purpose, with Marazza again providing the rationale for using the pure natural isomer.

4. Relief Requested

  • Petitioner requested that the Board institute an inter partes review and cancel 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 Patent 5,997,915 as unpatentable.