`571-272-7822
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` Paper No. 24
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` Entered: August 10, 2018
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`RIMFROST AS,
`Petitioner,
`
`v.
`
`AKER BIOMARINE ANTARCTIC AS,
`Patent Owner.
`____________
`
`Case IPR2017-00745
`Patent 9,078,905 B2
`____________
`
`
`
`Before ERICA A. FRANKLIN, TINA E. HULSE, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`HARLOW, Administrative Patent Judge.
`
`
`FINAL WRITTEN DECISION
`Determining That Claims 1–20 Have Been Shown to Be Unpatentable
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
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`RIMFROST EXHIBIT 1103 Page 0001
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`IPR2017-00745
`Patent 9,078,905 B2
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`I.
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`INTRODUCTION
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`Rimfrost AS (“Petitioner”) filed a Petition requesting an inter partes
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`review of claims 1–20 of U.S. Patent No. 9,078,905 B2 (Ex. 1001, “the
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`’905 patent”). Paper 2 (“Pet.”). Aker Biomarine Antarctic AS (“Patent
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`Owner”) declined to file a Preliminary Response.
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`On August 16, 2017, we instituted an inter partes review of all
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`challenged claims on all grounds asserted. Paper 9. On November 8, 2017,
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`Patent Owner filed a Patent Owner Response to the Petition. Paper 14 (“PO
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`Resp.”). On January 24, 2018, Petitioner filed a Reply to the Patent Owner
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`Response. Paper 17 (“Reply”).
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`We issue this Final Written Decision pursuant to 35 U.S.C. § 318(a)
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`and 37 C.F.R. § 42.73. Having considered the record before us, we
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`determine that Petitioner has shown by a preponderance of the evidence that
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`claims 1–20 of the ’905 patent are unpatentable. See 35 U.S.C. § 316(e).
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`A. Related Matters
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`The ’905 patent is asserted in Aker Biomarine Antarctic AS v. Olympic
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`Holding AS, Case No. 1:16-CV-00035-LPS-CJB (D. Del.). Pet. 2; Paper 3,
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`1. In addition, Petitioner has challenged, and we have instituted inter partes
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`review of, the claims of the ’905 patent in IPR2017-00747. Paper 5, 2.
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`Petitioner also challenges U.S. Patent No. 9,028,877 B2 (“the
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`’877 patent) in IPR2017-00746 and IPR2017-00748. Paper 5, 2. Both the
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`’905 patent and the ’877 patent are continuations of Application
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`No. 12/057,775, filed March 28, 2008.
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`2
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`The parties have not identified any further, currently pending, related
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`proceedings concerning the ’905 patent.1
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`B. The ’905 Patent
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`The ’905 patent, titled “Bioeffective Krill Oil Compositions,” issued
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`July 14, 2015, with Inge Bruheim, Snorre Tilseth, and Daniele Mancinelli as
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`the listed co-inventors. Ex. 1001, [54], [45], [72].
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`The ’905 patent describes extracts from Antarctic krill, small
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`shrimp-like animals, that include bioactive fatty acids. Ex. 1001, 1:19–20.
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`In particular, the ’905 patent discloses krill oil compositions having “high
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`levels of astaxanthin, phospholipids, includ[ing] enriched quantities of
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`ether phospholipids, and omega-3 fatty acids.” Id. at 9:28–31.
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`The ’905 patent states that myriad health benefits have been attributed
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`to krill oil in the prior art. For example, the ’905 patent states that “[k]rill oil
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`compositions have been described as being effective for decreasing
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`cholesterol, inhibiting platelet adhesion, inhibiting artery plaque formation,
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`preventing hypertension, controlling arthritis symptoms, preventing skin
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`cancer, enhancing transdermal transport, reducing the symptoms of
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`premenstrual symptoms or controlling blood glucose levels in a patient.”
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`Ex. 1001, 1:46–52. In addition, the ’905 patent recognizes that krill oil
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`compositions, including compositions having up to 60% w/w phospholipid
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`
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`1 The ’905 patent was also asserted in In the Matter of Certain Krill Oil
`Products and Krill Meal for Production of Krill Oil Products, Investigation
`No. 337-TA-1019 (USITC) (Pet. 2–3; Paper 3, 1); however, Petitioner states
`that the investigation has been “effectively terminated.” Paper 22, 3.
`3
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`content and as much as 35% w/w EPA/DHA content, were known in the art
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`prior to the time of invention. Id. at 1:52–57. The ’905 patent also indicates
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`that supercritical fluid extraction with solvent modifier was known to be a
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`useful method for extracting marine phospholipids from salmon roe. Id. at
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`1:65–67.
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`According to the ’905 patent, however, the solvent extraction methods
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`used in the prior art to isolate krill oil from the krill “rely on the processing
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`of frozen krill that are transported from the Southern Ocean to the
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`processing site,” which transportation is expensive and may result in the
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`degradation of the krill starting material. Id. at 2:3‒6. Such methods have
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`included steps of placing the material into a ketone solvent, such as acetone,
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`to extract the lipid soluble fraction, and recovering the soluble lipid fraction
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`from the solid contents using a solvent such as ethanol. Id. at 1:32‒40.
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`To overcome the above limitations, the ’905 patent discloses
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`“methods for processing freshly caught krill at the site of capture and
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`preferably on board a ship.” Id. at 10:18‒20. The ’905 patent explains that
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`the krill may be first subject to a protein denaturation step, such as a heating
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`step, to avoid the formation of enzymatically decomposed oil constituents.
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`Id. at 9:43‒50; 10:26‒31. Subsequently, the “oil can be extracted by an
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`optional selection of nonpolar and polar solvents including use of
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`supercritical carbon dioxide.” Id. at 9:51‒54.
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`In Example 7 of the ’905 patent, “[k]rill lipids were extracted from
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`krill meal (a food grade powder) using supercritical fluid extraction with
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`co-solvent.” Id. at 32:15‒16.
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`4
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`Initially, 300 bar pressure, 333°K and 5% ethanol
`(ethanol:CO2, w/w) were utilized for 60 minutes in order to
`remove neutral lipids and astaxanthin from the krill meal. Next,
`the ethanol content was increased to 23% and the extraction was
`maintained for 3 hours and 40 minutes. The extract was then
`evaporated using a falling film evaporator and the resulting krill
`oil was finally filtered.
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`Id. at 32:17‒23.
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`Example 8 of the ’905 patent prepared krill oil using the same method
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`described in Example 7, from the same krill meal used in that example.
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`Ex. 1001, 32:45‒46. The krill oil was then analyzed using 31P NMR
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`analysis to identify and quantify the phospholipids in the oil. Id. at 32:46‒
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`48. Table 222 shows the phospholipid profiles for the raw material, the final
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`product, and a commercially available krill oil, Neptune Krill Oil (“NKO”).
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`Id. at 33:6‒9. Table 22 is reproduced below:
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`
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`2 We view reference in the ’905 patent to “table 25” (Ex. 1001, 33:6‒9) to be
`an inadvertent typographical error, as the specification does not include a
`table 25. We understand Example 8 of the specification to refer, instead, to
`Table 22, which sets forth the described phospholipid profiles.
`5
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`Id. at 33:15‒39.
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`The ’905 patent teaches that the “main polar ether lipids of the krill
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`meal are alkylacylphosphatidylcholine (AAPC) at 7–9% of total polar lipids,
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`lyso-alkylacylphosphatidylcholine (LAAPC) at 1% of total polar lipids
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`(TPL) and alkylacylphosphatidyl-ethanolamine (AAPE) at <1% of TPL.”
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`Id. at 33:9‒14.
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`6
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`C. Illustrative Claim
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`Independent claim 1, reproduced below, is illustrative of the claimed
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`subject matter.
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`1.
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`Encapsulated krill oil comprising:
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`a capsule containing an effective amount of krill oil,
`said krill oil comprising from about 3% to about 15% w/w
`ether phospholipids.
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`Ex. 1001, 35:47–50. Independent claims 12 and 18 further specify the lipid
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`composition of the krill oil, the type of krill used, and the material in which
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`the krill oil is encapsulated. Id. at 36:29–36, 36:48–56.
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`D. Prior Art Relied Upon
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`Petitioner relies upon the following as prior art references (Pet. 8–9):
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`Randolph
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`US 2005/0058728 A1 Mar. 17, 2005
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`(Ex. 1011)
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`Catchpole
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`WO 2007/123,424
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`Nov. 1, 2007
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`(Ex. 1009)
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`Bottino, The Fatty Acids of Antarctic Phytoplankton and Euphausiids. Fatty
`Acid Exchange Among Trophic Levels of the Ross Sea, 27 MARINE BIOLOGY
`197–204 (1974) (Ex. 1007).
`
`Fricke et al., Lipid, Sterol and Fatty Acid Composition of Antarctic Krill
`(Euphausia superba Dana), 19(11) LIPIDS 821–827 (1984) (“Fricke 1984”)
`(Ex. 1010).
`
`Sampalis et al., Evaluation of the Effects of Neptune Krill Oil™ on the
`Management of Premenstrual Syndrome and Dysmenorrhea, 8(2) ALT.
`MED. REV. 171–179 (2003) (Ex. 1012).
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`Petitioner also relies on the Declaration of Stephen J. Tallon, Ph.D.
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`(Ex. 1006), and the Reply Declaration of Dr. Tallon (Ex. 1086).
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`7
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`Patent Owner relies on the Declaration of Nils Hoem, Ph.D.
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`(Ex. 2001).
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`E. Instituted Challenges
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`We instituted trial based on each challenge to the patentability of the
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`’905 patent presented in the Petition (Pet. 7):
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`Claim(s)
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`Basis
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`References
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`§ 103(a) Catchpole and Sampalis
`1–4, 9, and 10
`§ 103(a) Catchpole, Sampalis, and Randolph
`5
`6, 12, 15, 16, and 18 § 103(a) Catchpole, Sampalis, and Fricke 1984
`7, 8, 13, 14, 17, 19,
`Catchpole, Sampalis, Fricke 1984,
`and 20
`and Bottino
`11
`§ 103(a) Catchpole, Sampalis, and Bottino
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`§ 103(a)
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`II. ANALYSIS
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`A. Level of Ordinary Skill in the Art
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`The level of ordinary skill in the art is a factual determination that
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`provides a primary guarantee of objectivity in an obviousness analysis. Al-
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`Site Corp. v. VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing
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`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966); Ryko Mfg. Co. v. Nu-
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`Star, Inc., 950 F.2d 714, 718 (Fed. Cir. 1991)).
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`Petitioner asserts that a person of ordinary skill in the art at the time of
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`the invention of the ’905 patent would have had “an advanced degree in
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`marine sciences, biochemistry, organic (especially lipid) chemistry,
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`chemical or process engineering, or associated sciences,” as well as a
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`complementary understanding of “organic chemistry and in particular lipid
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`chemistry, chemical or process engineering, marine biology, nutrition, or
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`8
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`associated sciences; and knowledge of or experience in the field of
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`extraction,” in addition to “at least five years applied experience.” Pet. 6;
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`Ex. 1006 ¶ 27.
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`Patent Owner does not address the level of ordinary skill in its
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`Response; however, Patent Owner’s declarant, Dr. Hoem opines that the
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`definition proposed by Petitioner “is consistent with the literature,
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`credentials of individuals working on lipid extractions, and the skill
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`necessary to perform these extractions and interpret their results.” Ex. 2001
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`¶ 15. Based on that assessment, Dr. Hoem adopts the definition of the level
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`of ordinary skill in the art advanced by Petitioner. Id.
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`We agree with Petitioner, Dr. Tallon, and Dr. Hoem, and find that
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`Petitioner’s description of the level of ordinary skill in the art at the time of
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`invention of the ’905 patent is consistent with the type of problems
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`encountered in the art, prior art solutions to those problems, rapidity with
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`which innovations are made, sophistication of the technology, and
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`educational level of active workers in the field. See In re GPAC Inc., 57
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`F.3d 1573, 1579 (Fed. Cir. 1995). For purposes of this Decision, therefore,
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`we adopt Petitioner’s description. We also note that the applied prior art
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`reflects a level of skill at the time of the claimed invention consistent with
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`our determination. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed.
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`Cir. 2001).
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`In addition, we recognize each of Petitioner’s and Patent Owner’s
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`declarants as qualified to provide the proffered opinions on the level of skill
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`and the knowledge of a person of ordinary skill in the art at the time of the
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`invention. The relative weight that we assign such testimony, however, is
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`9
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`subject to additional factors. See, e.g., 37 C.F.R. § 42.65(a) (“Expert
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`testimony that does not disclose the underlying facts or data on which the
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`opinion is based is entitled to little or no weight.”); Office Patent Trial
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`Practice Guide, 77 Fed. Reg. 48,756, 48,763 (Aug. 14, 2012) (same).
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`B. Claim Construction
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`In an inter partes review, the Board interprets claim terms in an
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`unexpired patent according to the broadest reasonable construction in light
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`of the specification of the patent in which they appear. 37 C.F.R.
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`§ 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016)
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`(affirming applicability of broadest reasonable construction standard to inter
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`partes review proceedings). Under that standard, and absent any special
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`definitions, we give claim terms their ordinary and customary meaning, as
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`would be understood by one of ordinary skill in the art at the time of the
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`invention, in the context of the entire disclosure. In re Translogic Tech.,
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`Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Only those terms that are in
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`controversy need be construed, and only to the extent necessary to resolve
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`the controversy. Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co.
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`Ltd., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing Vivid Techs., Inc. v. Am.
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`Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
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`Although both Petitioner (Pet. 19‒25) and Patent Owner (PO Resp.
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`11‒13) offer several claim constructions, we determine that no explicit
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`construction of any claim term is necessary for purposes of this Decision. In
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`reaching this conclusion, we observe that the parties’ proposed constructions
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`are largely coextensive with each other, and to the extent those constructions
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`differ, they do so in ways that do not impact our analysis. For example, our
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`analysis below remains the same irrespective of whether we apply
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`Petitioner’s construction of “krill oil” as meaning “lipids extracted from
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`krill” (Pet. 20) or Patent Owner’s interpretation, “oil produced from krill”
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`(PO Resp. 11). Similarly, our analysis is unaffected by whether we apply
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`Petitioner’s definition of “effective amount of krill oil,” i.e., “at least the
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`range of between 0.2 and 10 grams of krill oil” (Pet. 21), or Patent Owner’s
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`construction, “0.2 grams to 10 grams of krill oil” (PO Resp. 12). 3
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`3 Patent Owner expressly accepts, for purposes of this proceeding,
`Petitioner’s proposed constructions of “polar solvent extract” and “plant
`phytonutrient,” the remaining terms for which the parties propose
`constructions. PO Resp. 12–13.
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`11
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`C. Overview of the Prior Art
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`Petitioner relies on combinations including Catchpole, Sampalis,
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`Fricke 1984, Randolph, and/or Bottino to support its contention that claims
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`1–20 of the ’905 patent would have been obvious. Pet. 6. Patent Owner
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`asserts that Fricke 1986,4 Tanaka,5 Prescott,6 and Zimmerman7 support its
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`argument that an ordinarily skilled artisan would not have made Petitioner’s
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`proposed combinations, and further, that the prior art teaches away from the
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`encapsulation of krill oil with high levels of ether phospholipids. See, e.g.,
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`PO Resp. 13–18. We provide an overview of each reference below.
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`1. Catchpole
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`Catchpole discloses “a process for separating lipid materials
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`containing phospholipids” (Ex. 1009, 1:5–6) in order to produce a product
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`containing “desirable levels of particular phospholipids” (id. at 3:27–28).
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`Catchpole states that phospholipids “have been implicated in conferring a
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`
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`4 Fricke et al., 1-O-Alkylglycerolipids in Antarctic Krill (Euphausia Superba
`Dana), 85B COMP. BIOCHEM. PHYSIOL. 131–134 (1986) (“Fricke 1986”)
`(Ex. 2006).
`
`5 Tanaka et al., Platelet-Activating Factor (PAF)-Like Phospholipids
`Formed During Peroxidation of Phosphatidylcholines from Different
`Foodstuffs, 59(8) BIOSCI. BIOTECH. BIOCHEM. 1389–1393 (1995) (Ex. 1014).
`
`6 Prescott et al., Platelet-Activating Factor and Related Lipid Mediators, 69
`ANNU. REV. BIOCHEM. 419–45 (2000) (Ex. 2003).
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`7 Zimmerman et al., The Platelet-Activating Factor Signaling System and Its
`Regulators in Syndromes of Inflammation and Thrombosis, 30 CRIT. CARE
`MED. S284–S301 (2002) (Ex. 2004).
`12
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`number of health benefits including brain health, skin health, eczema
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`treatment, anti-infection, wound healing, gut microbiota modifications, anti-
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`cancer activity, alleviation of arthritis, improvement of cardiovascular
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`health, and treatment of metabolic syndromes. They can also be used in
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`sports nutrition.” Id. at 1:29–2:2. Catchpole further discloses that products
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`having high levels of particular phospholipids “may be employed in a
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`number of applications, including infant formulas, brain health, sports
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`nutrition and dermatological compositions.” Id. at 25:9–13.
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`Catchpole describes, in Example 18, the fractionation of krill lipids
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`from krill powder using a process that employs supercritical CO2 in a first
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`extraction, and a CO2 and absolute ethanol mixture in a second. Id. at 24:1–
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`16. Table 16, reproduced below, reports the phospholipid concentrations
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`present in the krill oil extract obtained by Catchpole. Id. at Table 16.
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`
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`As shown in Table 16, the composition of Extract 2 includes 39.8%
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`phosphatidylcholine (“PC”). Id. The ether phospholipids
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`alkylacylphosphatidylcholine (“AAPC”) and
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`alkylacylphosphatidylethanolamine (“AAPE”) were also present in
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`Extract 2, representing 4.6% and 0.2%, respectively, of the extracted
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`composition. Id. In addition, summing each of the reported phospholipid
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`amounts reported for Extract 2 yields a total phospholipid concentration
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`of 45.1%. Id.
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`2. Sampalis
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`Sampalis describes a clinical trial “[t]o evaluate the effectiveness of
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`Neptune Krill OilT M (NKOT M) for the management of premenstrual
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`syndrome and dysmenorrhea.” Ex. 1012, 1. Sampalis explains that Neptune
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`Krill Oil is “extracted from Antarctic krill also known as Euphausia
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`superba. Euphausia superba, a zooplankton crustacean, is rich in
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`phospholipids and triglycerides carrying long-chain omega-3
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`polyunsaturated fatty acids, mainly EPA and DHA, and in various potent
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`antioxidants including vitamins A and E, astaxanthin, and a novel
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`flavonoid.” Id. at 4.
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`Sampalis discloses that each patient in the clinical trial was “asked to
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`take two 1-gram soft gels of either NKO or omega-3 18:12 fish oil (fish oil
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`containing 18% EPA and 12% DHA) once daily with meals during the first
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`month of the trial.” Id. Sampalis reports that “[t]he final results of the
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`present study suggest within a high level of confidence that Neptune Krill
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`Oil can significantly reduce the physical and emotional symptoms related to
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`premenstrual syndrome, and is significantly more effective for the
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`management of dysmenorrhea and emotional premenstrual symptoms than
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`fish oil.” Id. at 8.
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`3. Fricke 1984
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`Fricke 1984 discloses the “lipid classes, fatty acids of total and
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`individual lipids and sterols of Antarctic krill (Euphausia superba Dana)
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`from two areas of the Antarctic Ocean” as determined by thin layer
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`chromatography, gas liquid chromatography, and gas liquid
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`chromatography/mass spectrometry analyses. Ex. 1010, Abstract.
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`According to Fricke 1984, krill were collected and were quick frozen, and
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`lipids were extracted using the method of Folch.8 Id. at 1. Fricke 1984
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`teaches further that samples were also cooked on board “immediately after
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`hauling,” and were stored under the same condition. Id. at 2‒3.
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`Table 1 of Fricke 1984 is reproduced below.
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`Table 1 shows the total lipid content and the lipid composition data for the
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`two krill samples analyzed by Fricke 1984. Id. at 2. As indicated in
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`
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`8 Folch et al., A Simple Method for the Isolation and Purification of Total
`Lipides from Animal Tissues, 266 J. BIOL. CHEM. 497–509 (1957)
`(Ex. 1017).
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`Table 1, the krill samples respectively included approximately 33.3%
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`+/- 0.5% w/w and 40.4% +/- 0.1% w/w triacylglycerols. Id.
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`4. Randolph
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`Randolph discloses compositions for modulating cytokines to regulate
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`an inflammatory or immunomodulatory response including, inter alia,
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`rosehips and krill oil. Ex. 1011 ¶ 8. With regard to rosehips, Randolph
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`discloses that the composition may include one or more rosehip ingredients,
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`such as “dried rosehips, rosehip oil, and rosehip extracts.” Id. ¶ 24.
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`Concerning krill oil, Randolph discloses that
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`[a] composition of the invention can include krill oil. Krill oil
`can be obtained from any member of the Euphausia family, for
`example Euphausia superba. Conventional oil producing
`techniques can be used to obtain the krill oil. In addition, krill
`oil can be obtained commercially from Neptune Technologies
`and Bioresources of Quebec, Canada.
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`Id. ¶ 39. Randolph further explains that “[a] composition can contain any
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`amount of krill oil,” but will typically contain “between about 300 mg and
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`about 3000 mg of a krill oil ingredient.” Id. ¶ 40.
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`Randolph also discloses that, “[t]he ingredients of the composition can
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`be processed into forms having varying delivery systems. For example, the
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`ingredients can be processed and included in capsules, tablets, gel tabs,
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`lozenges, strips, granules, powders, concentrates, solutions, lotions, creams
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`or suspensions.” Ex. 1011 ¶ 46. Randolph further discloses that “[a] soft
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`gel capsule of the composition can be manufactured to include krill oil. This
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`capsule can be manufactured using conventional capsule manufacturing
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`techniques. The amount of krill oil in each capsule is about 300 mg.” Id.
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`¶ 52.
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`5. Bottino
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`Bottino observes that “[t]he study of krill has become intensive in
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`recent times, perhaps as a result of its potential importance as food,” and
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`explains that “[a] variety of organisms [are] usually included under that
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`generic name, but in the Southern Oceans the name Euphausia superba has
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`been considered almost a synonym for krill.” Ex. 1007, 1.
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`Bottino describes the fatty acid profiles for E. superba, E.
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`crystallorophias, and phytoplankton. Ex. 1007, Abstract. Bottino explains
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`that, in contrast to prior studies, lipids were extracted from E. superba
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`“immediately after capture.” Id. at 2. Euphausiids lipid extraction was
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`performed “with a chloroform:methanol (2:1, v/v) mixture,” as previously
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`described by Folch, and the fatty acids were analyzed using
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`chromatography. Id. at 1.
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`Table 1 of Bottino is reproduced below.
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`Ex. 1007, Table 1. Table 1 discloses the fatty acid content of E. superba
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`obtained from three different locations (i.e., stations) as a weight percent of
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`total fatty acids. Id. at 2. Notably, only those fatty acids present at 1% or
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`more as a weight percent of total fatty acids are included in Table 1. Id.
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`Table 1 n.c.
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`Table 3 of Bottino is reproduced below.
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`Ex. 1007, Table 3. Table 3 reports the identity and average amount of each
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`fatty acid present in the E. superba samples analyzed as a weight percent of
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`total fatty acids.
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`6. Fricke 1986
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`Fricke 1986 teaches that “[s]mall amounts of alkoxylipids, commonly
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`referred to as glyceryl ethers or ether lipids, are present in the lipids of many
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`marine animals.” Ex. 2006, 1. Fricke notes that “[w]hile investigating the
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`complete lipid composition of Antarctic Krill” in the study reported in
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`Fricke 1984, “there was some evidence for the presence of 1-O-
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`alkylglycerolipids in trace amounts,” which suggested “that some
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`degradation processes had taken place during storage.” Id. Fricke 1986
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`explains that the samples analyzed in Fricke 1984 “were frozen on board a
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`research vessel in 1977 and 1981 and could only be investigated after some
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`months of frozen storage.” Id. Accordingly, Fricke 1986 set out to verify
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`the findings of Fricke 1984, using lipid extracts from freshly caught krill that
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`were prepared on-board during an expedition in 1985. Id.
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`According to Fricke 1986, 1-O-alkylglycerolipids “were found as
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`minor lipid components,” and “ranged from 0.3 to 0.6% of total lipid content
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`of Antarctic Krill” (Ex. 2006, 2) as shown in Table 1, reproduced below.
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`Id. at Table 1.
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`With regard to the preparation of the 1977 and 1981 samples,
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`Fricke 1986 teaches that alkylglycerolipids were isolated after stepwise
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`hydrolysis of total lipids. Ex. 2006, 1. Phospholipids and neutral lipids
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`were separated using thin layer chromatography, and phospholipids were
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`incubated with phospholipase C. Id. Fricke 1986 teaches that the
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`alkylglycerols were prepared from the phospholipids and neutral lipids by
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`concentrated methanolic hydrochloric acid, and the alkylglycerols were
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`isolated using thin layer chromatography. Id. at 1–2. Concerning the 1985
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`samples, Fricke 1986 explains that those samples were treated “according to
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`Snyder et al. (1971) with Vitride (sodium-di-hydro-bis-(2-methoxyethoxy)-
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`aluminate) to form the free alkylglycerols.” Id.
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`7. Tanaka
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`Tanaka examines the “PAF-like lipids formed during peroxidation of
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`PCs from hen egg yolk, salmon roe, sea urchin eggs, and krill in an
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`FeSO4/EDTA/ascorbate system.” Ex. 1014, Abstract. Tanaka discloses the
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`phosphatidylcholine subclasses, and their relative amounts, present in
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`Antarctic krill (Euphausia superba) extract. Ex. 1014, 2, 3. Tanaka
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`explains that phosphatidylcholine was purified from crude krill lipid extract
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`using column chromatography and thin layer chromatography. Id. at 2.
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`Successive degradations of the purified extract using alkaline and acid
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`hydrolysis were then performed to measure the percentages of
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`phosphatidylcholine subclasses in the extract. Id.
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`Table 1 of Tanaka is reproduced below.
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`
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`Ex. 1014, Table 1. Table 1 shows that the ether phospholipid AAPC
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`accounted for 23.0% +/- 1.2% of the total phosphatidylcholine present in
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`Antarctic krill extract. Id. at 3.
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`Tanaka concludes that although the study “demonstrated the
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`formation of PAF-like phospholipids during peroxidation of PCs from
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`different foodstuffs[,] . . . the occurrence of PAF-like lipids in some stored
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`foods is still speculative and requires further investigation.” Ex. 1014, 5.
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`8. Prescott
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`Prescott discloses that PAF “is a phospholipid with potent, diverse
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`physiological actions, particularly as a mediator of inflammation.”
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`Ex. 2003, Abstract. Prescott explains that
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`[t]he PAF receptor recognizes the sn-1 ether bond of PAF, its
`short sn-2 acetyl residue, and the choline head group; alteration
`of any of these structures greatly decreases signaling through the
`PAF receptor. Extension of the sn-2 acetyl residue by one
`methylene is without consequence, but extension by two
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`methylenes decreases activity by a factor of 10- to 100-fold,
`depending on the assay. Extension beyond this results in the loss
`of signaling through the PAF receptor.
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`Ex. 2003, 13 (internal citations omitted).
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`Prescott further discloses that “[o]xidation of complex lipids in
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`reduced systems has defined potential oxidation pathways and products, but
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`whether such oxidizing conditions exist in vivo is problematic, given the
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`unstable nature of the reactive intermediates and the potential of metabolism
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`of the oxidation products.” Ex. 2003, 14.
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`9. Zimmerman
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`Zimmerman is a review article that teaches that “[t]he PAF signaling
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`system can trigger inflammatory and thrombotic cascades, amplify these
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`cascades when acting with other mediators, and mediate molecular and
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`cellular interactions (cross talk) between inflammation and thrombosis.”
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`Ex. 2004, Abstract. Zimmerman explains that artificial oxidation of
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`phosphatidylcholines “generates a large series of phospholipids in which the
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`polyunsaturated fatty acid at the sn-2 position . . . is fragmented to shorter
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`chain lengths. Some of these oxidized phospholipids have sufficiently short
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`sn-2 residues and other structural features that allow them to be recognized
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`by the PAF receptor.” Id. at 4–5.
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`D. Obviousness Based on
`Catchpole and Sampalis
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`Petitioner asserts that claims 1–4, 9, and 10 are unpatentable under
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`§ 103(a) as obvious in view of Catchpole and Sampalis. Pet. 26–34. Patent
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`Owner disagrees. PO Resp. 13–18.
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`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
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`differences between the claimed subject matter and the prior art are such that
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`the subject matter, as a whole, would have been obvious at the time the
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`invention was made to a person having ordinary skill in the art to which said
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`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
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`(2007). The question of obviousness is resolved on the basis of underlying
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`factual determinations including: (1) the scope and content of the prior art;
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`(2) any differences between the claimed subject matter and the prior art;
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`(3) the level of ordinary skill in the art; and, where presented, (4) objective
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`evidence of nonobviousness. Graham, 383 U.S. at 17–18.
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`“An obviousness determination requires finding both ‘that a skilled
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`artisan would have been motivated to combine the teachings of the prior art
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`references to achieve the claimed invention, and that the skilled artisan
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`would have had a reasonable expectation of success in doing so.’” CRFD
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`Research, Inc. v. Matal, 876 F.3d 1330, 1340 (Fed. Cir. 2017) (quoting
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`Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367–
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`1368 (Fed. Cir. 2016)).
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`In assessing whether an ordinarily skilled artisan would have had
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`reason to combine known elements in order to arrive at the claimed
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`invention, it will often “be necessary for a court to look to interrelated
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`teachings of multiple patents; the effects of demands known to the design
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`community or present in the marketplace; and the background knowledge
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`possessed by a person having ordinary skill in the art.” KSR, 550 U.S. at
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`418. A reference may be said to teach away from such combination “when a
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`person of ordinary skill, upon reading the reference, would be discouraged
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`from following the path set out in the reference, or would be led in a
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`direction divergent from the path that was taken by the [patentee].” DePuy
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`Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed.
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`Cir. 2009) (quoting Ricoh Co., Ltd. v. Quanta Comput. Inc., 550 F.3d 1325,
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`1332 (Fed. Cir. 2008)). In analyzing whether a reference teaches away from
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`the claimed invention, that reference “must [be] considered for all it taught,
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`disclosures that diverged and taught away from the invention at hand as well
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`as disclosures that pointed towards and taught the invention at hand.”
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`Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 296
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`(Fed. Cir. 1985) (citation omitted). A reference does not tea