Prior art

Analysis of Prior Art for U.S. Patent 12,252,506

Washington, D.C. - An analysis of the prior art cited during the prosecution of U.S. Patent 12,252,506, titled "Methods of preparing nicotinamide riboside and derivatives thereof," has been conducted to determine the novelty and non-obviousness of the patented claims. The patent, issued on March 18, 2025, is assigned to The Queen's University of Belfast and exclusively licensed to Niagen Bioscience, Inc.

The invention provides methods for preparing nicotinamide riboside (NR) and its derivatives with specific, pharmaceutically acceptable anions, addressing shortcomings in previous synthesis methods that resulted in toxic or unstable salt forms.

Below is an assessment of the most pertinent prior art and its potential impact on the claims of the '506 patent.

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Key Prior Art References and Their Potential Anticipation of Claims:

The following references were central to the examination of the patent application and are the most relevant to understanding the landscape at the time of the invention.

1. International Patent Application WO 2007/061798 A2

• Full Citation: Sauve, Anthony A., and Samuel A. J. Trammell. "Process for the preparation of nicotinamide riboside and its derivatives." WO 2007/061798 A2, filed November 21, 2006, and published May 31, 2007.
• Brief Description: This international application discloses a method for synthesizing nicotinamide riboside and its derivatives. A key step in this process is the use of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a catalyst. This results in the formation of NR as a triflate (-OTf) salt. The '506 patent explicitly distinguishes itself from this method, noting that triflate salts are unsuitable for nutritional supplements due to toxicity.
• Potential Anticipation under 35 U.S.C. § 102:
  • Claims 1, 6, 8, 9, and other composition claims: This reference does not anticipate the composition claims of the '506 patent because the claims in the '506 patent specifically exclude trifluoromethanesulfonate and formate anions, instead claiming NR with other, more desirable anions like acetate, ascorbate, lactate, and aminodicarboxylic acids. WO 2007/061798 teaches away from these claimed compositions by focusing on the triflate salt.
  • Claims 13 and 18 (Method Claims): This reference does not anticipate the method claims. The core of claims 13 and 18 is the anion exchange step, where a starting trifluoromethanesulfonate compound is converted to a different salt form using a nitrogen-containing cation (Z+X-). The Sauve application describes the initial synthesis to create the triflate salt but does not teach the specific anion exchange method claimed in the '506 patent.

2. Tanimori, S., et al., Bioorganic & Medicinal Chemistry Letters, 2002, 12, 1135-1137

• Full Citation: Tanimori, S., Ohta, T., & Kirihata, M. (2002). A new and efficient synthesis of nicotinamide riboside. Bioorganic & Medicinal Chemistry Letters, 12(8), 1135–1137.
• Brief Description: This scientific paper describes a laboratory-scale synthesis of nicotinamide riboside. Similar to the Sauve application, this method also utilizes TMSOTf as a catalyst, leading to the formation of the triflate salt of NR. The '506 patent itself notes that this method is not stereoselective and produces undesirable anomers.
• Potential Anticipation under 35 U.S.C. § 102:
  • Composition Claims (e.g., 1, 6): For the same reasons as with WO 2007/061798, this reference does not anticipate the composition claims. The Tanimori paper describes the triflate salt, while the '506 patent claims compounds with different, specified anions.
  • Method Claims (e.g., 13, 18): This reference does not anticipate the method claims as it does not disclose the claimed anion exchange process to replace the triflate ion with a more suitable one.

3. Franchetti, P., et al., Bioorganic & Medicinal Chemistry Letters, 2004, 14, 4655-4658

• Full Citation: Franchetti, P., Pasqualini, M., Petrelli, R., Ricciutelli, M., Vita, P., & Cappellacci, L. (2004). Synthesis and biological evaluation of nicotinamide β-riboside analogues as inhibitors of nicotinamide phosphoribosyltransferase. Bioorganic & Medicinal Chemistry Letters, 14(18), 4655–4658.
• Brief Description: This paper also describes a synthesis route for nicotinamide riboside analogues. The synthetic strategy presented again results in the triflate salt of the final compound, leveraging the catalytic properties of TMSOTf.
• Potential Anticipation under 35 U.S.C. § 102:
  • Composition Claims: This reference does not anticipate the claimed compositions of the '506 patent. The focus is on the triflate salt, which is explicitly carved out from the scope of the key independent claims of the '506 patent.
  • Method Claims: The Franchetti paper does not anticipate the claimed methods. It details the initial synthesis but does not teach the specific anion exchange reaction that is a critical step in claims 13 and 18 of the '506 patent.

Conclusion

The prior art cited against U.S. Patent 12,252,506, particularly WO 2007/061798, Tanimori et al., and Franchetti et al., consistently describes methods of producing nicotinamide riboside that result in a triflate salt. The '506 patent successfully carves out a novel and non-obvious invention by focusing on compositions with specific, non-triflate anions and by claiming a method to achieve this through a specific anion exchange process. The prior art does not teach or suggest the claimed compositions or the specific method for their preparation. Therefore, based on the cited references, the claims of U.S. Patent 12,252,506 appear to be valid over this prior art.