Opinion ID: 4189524
Heading Depth: 3
Heading Rank: 1

Heading: e., oils derived from plants. Id. at 5.

Text: Motoyama describes several examples in which CoQ10 was dissolved in l-carvone, after which the formulation was placed in capsules. Motoyama at 5-7. The capsules were orally administered to beagle dogs, and the 8 SOFT GEL TECHNOLOGIES, INC. v. JARROW FORMULAS, INC. resulting concentration of CoQ10 in the dogs’ blood was measured. Id. at 6. The observed effect of the CoQ10 formulation was the “high bioavailability [of CoQ10] and particularly good absorption in the digestive tract, and . . . a large area under the curve (AUC) of concentration [of CoQ10] in the blood.” Id. at 2; see also id. at 6-7 (Tables 1-2). The next two references have overlapping disclosures; the first is a patent, and the second is a dissertation on which that patent is based. The patent, U.S. Patent No. 7,588,786 (“Khan ’786 patent”), was issued in September 2009 to Khan and Nazzal. It claims priority to a provisional application filed in November 2001. The dissertation, authored by Nazzal, is dated August 2002 (“Nazzal”). Both references note the poor solubility of CoQ10 in aqueous solvents such as water, and both posit that solvents such as lipids or oils could be used instead. See Nazzal at x; Khan ’786 patent, col. 1, ll. 21-26. The idea was to make an oil mixture consisting of oil and CoQ10, and then introduce the oil mixture into the body, where it would encounter an aqueous environment. See Nazzal at 17-19; Khan ’786 patent, col. 1, ll. 28-30. Although oil does not dissolve in water, Nazzal noted that substances known as emulsifiers could be included in the oil mixture. Nazzal at 19-22. The emulsifiers would allow the oil mixture to disperse in the body as small droplets of oil in the body’s aqueous fluids. Id.; see also Khan ’786 patent, col. 1, ll. 28-30. The dispersion of oil droplets in water is called an emulsion—or a micro- or nano-emulsion, depending on the size of the oil droplets in the water. See Nazzal at 16-17; Khan ’786 patent, col. 1, ll. 26-30. The formulation of CoQ10, oil, and emulsifiers is referred to as a self-emulsifying drug delivery system (“SEDDS”), a selfmicroemulsifying drug delivery system (“SMEDDS”), or a self-nanoemulsifying drug delivery system (“SNEDDS”). The distinction among the three systems depends on the size of the oil droplets formed when the oil mixture is SOFT GEL TECHNOLOGIES, INC. v. JARROW FORMULAS, INC. 9 introduced into water. Nazzal at 19; Khan ’786 patent, col. 1, ll. 26-30; id., col. 2, ll. 52-55. For the oil mixture, Nazzal and Khan tested CoQ10 with various essential (volatile) oils, including peppermint oil, spearmint oil, and lemon oil, as solvents. See Nazzal at 13-14, 115-18; Khan ’786 patent, col. 4, ll. 28-31 & Fig. 4. The goal was to obtain an oil mixture in which the CoQ10 was completely melted at 37ºC, the average human body temperature. Nazzal at 112; Khan ’786 patent, col. 6, line 65, through col. 7, line 2. That would avoid the problem of administering a capsule containing CoQ10 as a suspension (a solid precipitate in the oil), which is not an effective delivery method. Nazzal at 112; see also Khan ’786 patent, col. 1, ll. 59-62. Instead, after ingestion of the capsule and exposure to body temperatures, the CoQ10 would melt in the oil, facilitating absorption by the body. See Nazzal at 26, 112; Khan ’786 patent, col. 2, ll. 55-61. Pure CoQ10 has a melting temperature of 51ºC, far above body temperature. Khan ’786 patent, col. 6, ll. 1315 & Fig. 1. But the Khan ’786 patent and Nazzal dis- close that CoQ10 can be mixed with a sufficient amount of an essential oil to lower its melting temperature. See Nazzal at 116-18 (Figs. 4.9-11); Khan ’786 patent, col. 6, ll. 36-40 & Figs. 3-4. Khan and Nazzal further disclose that when mixed with an essential oil, the CoQ10 would melt at a lower temperature even after adding an emulsifier to prepare the SNEDDS. See Nazzal at 121-23; Khan ’786 patent, col. 7, ll. 48-51 & tbl.2. The Nazzal dissertation concludes with a list of six “[r]ecommendations for future studies.” Nazzal at 246. The second and third recommendations on the list are to study “[t]he exact nature of the interaction that exists between CoQ[10] and essential oils” in lowering the melting point of CoQ10, and to study the “[c]hemical components of essential oils such as limonene, menthone, 10 SOFT GEL TECHNOLOGIES, INC. v. JARROW FORMULAS, INC. and carvone . . . for their potency in” lowering the melting point of CoQ10. Id. The fourth reference relied on by the Board was 1 Giovanni Fenaroli, Fenaroli’s Handbook of Flavor Ingredients 389 (2d ed. 1975) (“Fenaroli”). That reference notes that lemon essential oil has many different components, but “contains approximately 90% limonene (by weight).” The fifth reference cited by the Board is a monograph published by the World Health Organization’s International Agency for Research on Cancer (“IARC”). 56 IARC, Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins (1993). The monograph states that limonene is “the most frequently occurring natural monoterpene.” Id. at 135. The monograph further explains that limonene occurs naturally in the d- and l- forms, and that “the d form comprises 98-100% of the limonene in most citrus oils.” Id. In each of the three decisions at issue in this case, the Board found that (1) Motoyama teaches dissolving CoQ10 in carvone, a monoterpene found in spearmint oil and peppermint oil, and then encapsulating the solution; (2) the Khan ’786 patent and Nazzal teach the use of essential oils, including peppermint oil, spearmint oil, and lemon oil, in conjunction with CoQ10; and (3) IARC and Fenaroli teach that d-limonene (a monoterpene) is the main constituent of lemon oil. 2 The Board determined 2 In the decisions addressing the ’072 and ’583 pa- tents, the Board found that d-limonene was “the main constituent” of lemon oil. In the decision on rehearing regarding the ’826 patent, the Board found that d- limonene was “one of the main constituents” of lemon oil. That discrepancy is not material to resolution of the SOFT GEL TECHNOLOGIES, INC. v. JARROW FORMULAS, INC. 11 that the combination of those references suggests the invention claimed in the Soft Gel patents—i.e., using d- limonene, as Motoyama had used carvone, to dissolve CoQ10 for oral formulations. The Board also found that a person of skill in the art would have been motivated to combine those references and would have had a reasonable expectation of success in doing so. Ultimately, the Board invalidated, on obviousness grounds, claims 1-24 of the ’072 patent; claims 1-2, 4, 6-10, 12-13, and 15-17 of the ’583 patent; and claims 1-2, 5, 7, and 6-15 of the ’826 patent. 3 On appeal, Soft Gel challenges as erroneous the Board’s factual findings (1) that d-limonene is the main constituent of lemon oil, (2) that the Khan ’786 patent does not teach away from the claimed invention, and (3) that a person of ordinary skill would have had a reasonable expectation of success regarding the combination.