`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_______________________
`
`RIMFROST AS
`
`Petitioner
`
`v.
`
`AKER BIOMARINE ANTARCTIC AS
`
`Patent Owner
`
`_______________________
`
`IPR2018-01730
`
`U.S. Patent No. 9,072,752
`
`_______________________
`
`
`REPLY AND OPPOSITION
`
`DECLARATION OF DR STEPHEN J. TALLON
`
`
`
`RIMFROST EXHIBIT 1086 Page 0001
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`IPR2018-01730
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`U.S. Patent No. 9,072,752
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`TABLE OF CONTENTS
`
`
`TABLE OF CONTENTS ........................................................................................... i
`I. DECLARATION OF DR STEPHEN J. TALLON ........................................... 1
`II. BASIS FOR OPINION ...................................................................................... 1
`III.
`INVALIDITY GROUNDS, CLAIMS AND AMENDED CLAIMS ........... 6
`‘752 Patent Petition Invalidity Grounds ................................................................ 6
`‘752 Patent Independent Claims Summary ........................................................... 7
`‘752 Patent Amended Claims Invalidity Grounds ................................................. 8
`‘752 Patent Amended Independent Claims Summary ........................................... 9
`IV.
`PATENT OWNER’S VALIDITY ARGUMENTS FAIL ...........................10
`A. First, PO argues that none of the references, including Catchpole (Exhibit
`1009) disclose krill oil with greater than 5%, 6%, 7% and from 6% to 10% (in
`the amended claims) ether phospholipids - PO is wrong. ...................................10
`Catchpole discloses expressly in an example: (a) a krill feed material
`containing 0.7 wt% ether phospholipids, (b) a krill oil extracted from the krill
`feed material containing at least 4.8 wt% ether phospholipids, and (c) methods
`for producing said krill oil. ..............................................................................11
`Catchpole discloses that krill meal is a preferred substrate for producing a
`krill oil with the claimed ether phospholipids levels of greater than 5%,
`greater than 10%, and even higher. ..................................................................13
`Catchpole discloses methods and conditions to use for producing krill oils
`with enriched levels of ether phospholipids. ...................................................19
`Catchpole discloses even further methods, conditions, and examples, that
`describe how to produce a krill oil from krill meal with ether phospholipid of
`greater than 5%, 6%, 7%, or higher. This is demonstrated with some
`calculated examples. ........................................................................................25
`Summary. Catchpole anticipates greater than about 5%, 6%, 7%, and ranges
`of 6% to 10% (in the amended claims) and higher ether phospholipid content
`in a krill oil. ......................................................................................................31
`
`
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`i
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`U.S. Patent No. 9,072,752
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`B. Second, PO argues that Catchpole’s Example 18’s 4.8% level of ether PLs
`is the highest obtainable, and that since Enzymotec does not disclose its
`extraction technique a POSITA would not use Catchpole’s ratio of ether PL to
`PL to determine the amount of ether PL in Enzymotec’s krill oil products – PO
`is wrong. ...............................................................................................................33
`(i) Catchpole’s Extract 2 already contains more than 4.8% ether PL because
`of the presence of ether LysoPLs that were not disclosed. ..............................33
`(ii) A POSITA would consider Enzymotec’s krill oil composition
`disclosure of PL as a disclosure of ether PL as well, in approximately the ratio
`provided by Catchpole. ....................................................................................34
`(iii) Enzymotec GRAS (Exhibit 1048) discloses krill oil extracts with ether
`PL content of 5% to 9.7%. ...............................................................................42
`C. Third, PO argues that because it “believes” that there were no neutral lipids
`left in Catchpole’s Example 18 Extract 2 and that removal of neutral lipids is the
`only way to increase the ether PL content of Extract 2, a POSITA could not use
`removal of neutral lipids from Extract 2 to increase the ether PL content in
`Catchpole’s Extract 2 to greater than 4.8%, - PO is wrong. ................................43
`(i) Catchpole’s Extract 2 Contains Has Neutral Lipids. ...............................43
`(ii) Removal of some of the neutrals in Catchpole Extract 2, would by
`itself increase the concentration of ether phospholipids in the krill oil extract.
`
`59
`(iii) PO’s arguments regarding the lack of neutrals in Catchpole’s Extract 2
`are wrong. .........................................................................................................60
`(iv) POSITA could have modified Catchpole’s Extract 2 and/or the
`processes, methods and conditions as disclosed in Catchpole to to provide a
`krill oil extract with the claimed levels of PL including ether PL, with
`predictability and a reasonable expectation of success. ...................................71
`D. Fourth, PO argues that alleged concerns about PAF would have lead a
`POSITA to limit the ether PL content in their krill oil compositions – PO is
`wrong....................................................................................................................71
`(i) Prior art cited by PO does not support PAF concern. ..............................72
`(ii) No Mention Of PAF In Three Krill Oil GRAS Filings By Different
`Companies Including PO’s GRAS Notification ..............................................96
`(iii) Motivation to Combine was Strong ....................................................114
`
`
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`ii
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`(iv) Prior Art Supports Motivation To Increase Phospholipids And Ether
`Phospholipids And To Combine ....................................................................116
`(v) Murata (Exhibit 1122) Discloses That Large Amounts of Krill Oil
`Were Useful as Platelet Aggregation Inhibitors -The Exact Opposite of the
`effect if Krill Oil Extracts caused an increase PAF or PAF-like activity. .....125
`E. Fifth, PO argues that none of the prior art references teaches or suggests
`producing a krill oil containing “astaxanthin esters in amount of from 100 mg/kg
`to 700 mg/kg of said krill oil” (in the amended claims) – PO is wrong. ...........126
`(i) A NKO krill oil had 472 mg/kg astaxanthin esters) ..............................126
`(ii) Randolph discloses krill oil compositions with any amount of
`astaxanthin esters including 158 mg/kg astaxanthin esters. ..........................128
`(iii) Sampalis II (Exhibit 1013) discloses 200 mg/kg and 100 mg/kg
`astaxanthin .....................................................................................................130
`(iv) Motivations to increase, decrease and maintain astaxanthin content. 133
`FRICKE II (1986) (EXHIBIT 2006) VALUE FOR ETHER PHOSPHOLIPIDS IN
`KRILL IS TOO LOW, UNHEARD OF AND EVEN THE WAY IT IS
`CALCULATED IS MISLEADING. .....................................................................136
`(i) Fricke II Destroys the Ether Phospholipids before Quantifying their
`Amount ...........................................................................................................138
`(ii)
`Fricke II Discloses Different Values of Ether Phospholipid Content138
`(iii) Fricke II Does Not Use a Direct Measurement of Ether Phospholipid
`Content ...........................................................................................................140
`(iv) NMR- The direct method of measuring ether phospholipids. ............143
`(v) A POSITA Would Estimate That Fricke Had a Higher Ether
`Phospholipid Content .....................................................................................146
`THE PROPERTIES OF DIFFERENT SOLVENT SYSTEMS WERE WELL
`KNOWN TO POSITA. PO’S REPRESENTATION OF DIFFERENT
`EXTRACTIONS AS ‘SELECTIVE’ AND ‘NON-SELECTIVE’ IS
`IRRELEVANT. ......................................................................................................148
`CONCLUSION ......................................................................................................153
`
`
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`IPR2018-01730
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`
`
`I.
`
`
`
`U.S. Patent No. 9,072,752
`
`DECLARATION OF DR STEPHEN J. TALLON
`
`
`
`1.
`
`
`I make this declaration in support of Petitioner’s Reply to Patent
`
`Owner’s Response to Petition (Papers No. 13) in IPR2018-01730 (“POR1730”).
`
`2.
`
`I also make this declaration in support of Petitioner’s Opposition to
`
`Patent Owner’s Contingent Motion to Amend the Claims (Papers No. 12) in
`
`IPR2018-0730 (“MTA1730”).
`
`
`II. BASIS FOR OPINION
`
`I have reviewed the Declaration of Dr. Nils Hoem, Exhibit 2001
`
`
`3.
`
`(“Hoem Dec.”), and POR1730 and disagree with their conclusions overall and as
`
`described in detail in the discussion below. Furthermore, after reviewing the
`
`foregoing, I hereby reaffirm my opinion from my earlier Declaration, Exhibit
`
`1006, that all claims of U.S. Patent 9,072,752 (“the ‘752 Patent”) would have been
`
`obvious to a POSITA in view of the prior art cited.
`
`4.
`
`I have also reviewed the Declaration of Dr. Nils Hoem, Exhibit 2001
`
`(“Hoem Dec.”), and MTA1730 and disagree with their conclusions overall and as
`
`described in detail in the discussion below.
`
`
`
`1
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`5.
`
`In forming my opinion herein, I have relied on my own education,
`
`work experiences and knowledge, see my CV in my declaration, Exhibit 1006,
`
`Appendix D, my review of the documents referenced in the Tallon Dec. (Exhibit
`
`1006), and, in addition to my review of POR1730, MTA1730, the declaration of
`
`Dr. Hoem (Exhibit 2001), and my review of the following documents:
`
`
`EXHIBIT NO.
`
`1075
`
`
`1079
`
`
`1089
`
`
`1090
`
`
`1091
`
`1094
`
`
`
`EXHIBIT DESCRIPTION
`
`Neptune, GRAS Notice [No. GRN 000242] for “High
`Phospholipid Krill Oil”
`https://www.fda.gov/downloads/Food/IngredientsPackagingLab
`eling/GRAS/NoticeInventory/ucm269133.pdf, dated January
`18, 2008 and filed by the FDA February 4, 2008 (Neptune
`GRAS).
`
`Burri, L., Hoem, N., et al., “Fingerprinting Krill Oil by 31P,
`1H and 13C NMR Spectroscopies”, J Am Oil Chem Soc (2016)
`93:1037-1049 (Burri).
`
`Aker GRAS [No. GRN 000371], “Notification of GRAS
`Determination of Krill Oil”, December 14, 2010.
`https://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=GR
`ASNotices&id=371
`
`Deposition Transcript of Dr. Nils Hoem, January 10, 2018
`(IPR2017-00745, inter alia).
`
`Neptune GRAS Agency Response Letter GRN 000242.
`
`Marathe, et al., Inflammatory Platelet-activating Factor-like
`Phospholipids in Oxidized Low Density Lipoproteins Are
`Fragmented Alkyl Phosphatidylcholines, J Biol Chem. 1999
`Oct 1;274(40):28395-28404.
`
`2
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`RIMFROST EXHIBIT 1086 Page 0006
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`IPR2018-01730
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`
`1095
`
`
`1107
`
`
`1109
`
`1121
`
`
`1122
`
`1124
`
`
`1128.
`
`
`1140
`
`
`1141
`
`1142
`
`1143
`
`1145
`
`1146
`
`
`
`
`
`U.S. Patent No. 9,072,752
`
`Stremler, et al., Human Plasma Platelet-activating Factor
`Acetylhydrolase - Oxidatively Fragmented Phospholipids As
`Substrates, (1991) J. Biol. Chem. 266, 11095–11103.
`
`Winther, Hoem, et al., Elucidation of phosphatidylcholine
`composition in krill oil extracted from Euphausia superba,
`Lipids. 2011 Jan;46(1):25-36. doi: 10.1007/s11745-010-3472-6.
`Epub 2010 Sep 17.
`
`Aker GRAS Agency Response Letter GRN 000371.
`
`Declaration by Nils Hoem in Support of Request for Inter
`Partes Reexamaination of U.S. Patent No. 8,057,825, Control
`No. 95/001,819, executed September 16, 2011.
`
`Japanese Laid Open Publication S63-23819 (Murata).
`
`Itano Refrigerated Food Co., Ltd., Bio & High Technology
`Announcement and Natural Astaxanthin & Krill Lecithin, pp.
`1-16, Exhibit 1124 (“Itano”).
`
`Deposition Transcript of Dr. Nils Hoem held on July 2, 2019
`(IPR2018-01178 & IPR2018-01179.)
`
`U.S. Patent No. 8,372,812, Tilseth & Hoem, et al.,
`“Phospholipid and Protein Tablets,” (“Tilseth”).
`
`Paper 12 PO’s Motion to Amend (IPR2018-01730).
`
`USP42-NF37, “Krill Oil”.
`
`USP42-NF37, “Krill Oil Capsules”.
`
`Deposition of Dr. Hoem, August 15, 2019 (IPR2018-01730).
`
`Acid Number to FFA Conversions _ Biodiesel Chemistry, Rick
`Da Tech, Make Biodiesel (2019) www.make-
`biodiesel.org/Biodiesel-Chemsitry/acid-number-to-ffa-
`conversions.html.
`
`3
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`
`
`1147
`
`
`1148
`
`
`1149
`
`
`1150
`
`2002
`
`
`2003
`
`2004
`
`
`
`
`
`
`
`
`
`U.S. Patent No. 9,072,752
`
`Standard for Fish Oils [including krill oil], CODEX STAN 329-
`2017, Codex Alimentarius Commission, Food and Agriculture
`Organization of the United Nations, World Health
`Organization, http://www.fao.org/fao-who-
`codexalimentarius/sh-
`proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao
`.org%252Fsites%252Fcodex%252FStandards%252FCXS%2B3
`29-2017%252FCXS_329e.pdf
`
`European Food Safety Authority, “Safety of ‘Lipid extract from
`Euphausia superba' as a novel food ingredient”, Scientific
`Opinion of the Panel on Dietetic Products, Nutrition and
`Allergies (EFSA)-2009-EFSA_Journal.
`
`Joint FAO/WHO Food Standards Programme, Codex
`Committee on Fats and Oils, Kuala Lumpur, Malaysia, 27
`February - 3 March 2017, Draft Codex Standard for Fish Oils
`[including krill oil] - comments included, CRD17, Codex
`Alimentarius Commission, Food and Agriculture Organization
`of the United Nations, World Health Organization,
`http://www.fao.org/fao-who-codexalimentarius/sh-
`proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao
`.org%252Fsites%252Fcodex%252FMeetings%252FCX-709-
`25%252FCRD%252Ffo25_CRD17x.pdf
`
`Declaration of Robert S. McQuate (IPR2018-00295).
`
`Yamaguchi, K. et al. “Supercritical Carbon Dioxide Extraction
`of Oils from Antarctic Krill”, J. Agric. Food Chem. 1986, 34,
`904-907.
`
`
`
`
`
`Prescott, S. et al. “Platelet-Activating Factor and Related Lipid
`Mediators”, Annu. Rev. Biochem. 2000. 69:419-45.
`
`Zimmerman, G. et al. “The platelet-activating factor signaling
`system and its regulators in syndromes of inflammation and
`thrombosis”, Crit. Care Med 2002, Vol. 30, No. 5 (Suppl):
`S294-S301.
`
`4
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`
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`
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`
`
`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`2005
`
`2006
`
`
`
`
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`2020
`
`
`
`2022
`
`
`
`2024
`
`
`
`
`
`
`
`
`
`U.S. Patent No. 9,072,752
`
`
`Calder, P. “n-3 Polyunsaturated fatty acids, inflammation, and
`inflammatory diseases1-3”, Am. J. Clin. Nutr. 2006; 83(suppl):
`1505S-19S.
`
`Fricke, H. et al. “1-O-Alkylglycerolipids in Antarctic Krill
`(Euphausia Superba DANA)”, Comp. Biochem. Physiol. Vol.
`85B, No. 1, pp. 131-134, 1986.
`
`Tallon Reply Dec. (IPR2017-00745, Exhibit 1086)
`
`Zierenberg et al., Intestinal absorption of
`polyenephosphatidylcholine in man, J. Lipid. Res. (1982)
`23:1136-1142.
`
`Blank et al., Meats and fish consumed in the American diet
`contain substantial amounts of ether-linked phospholipids. J
`Nutr. (1992) 122(8):1656-61.
`
`Hartvigsen et al., 1-O-Alkyl-2-(w-oxo)acyl-sn-glycerols from
`Shark Oil and Human Milk Fat Are Potential Precursors of PAF
`Mimics and GHB. Lipids (2006) 41, 679–693.
`
`Marathe et al., Inflammatory Platelet-activating Factor-like
`Phospholipids in Oxidized Low Density Lipoproteins Are
`Fragmented Alkyl Phosphatidylcholines. J. Biol. Chem. (1999)
`274(40):28395-28404.
`
`Transcript of Deposition of Dr. Stephen Tallon, June 4, 2019
`(IPR2018-01730).
`
`Transcript of Deposition of Dr. Stephen Tallon, December 12,
`2018 (IPR2018-00295).
`
`Transcript of Deposition of Dr. Stephen Tallon, August 29,
`2018 (IPR2018-00295).
`
`
`
`5
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`U.S. Patent No. 9,072,752
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`IPR2018-01730
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`
`
`III.
`
`INVALIDITY GROUNDS, CLAIMS AND AMENDED CLAIMS
`
`
`
`
`‘752 Patent Petition Invalidity Grounds
`
`
`
`6.
`
`A summary chart of the ‘752 Patent Petition Invalidity Grounds is
`
`included below for reference.
`
`
`
`
`
`
`
`
`Ground
`
`1
`
`Reference(s)
`
`Basis
`
`Catchpole
`
`35 U.S.C. § 102(e)
`
`2
`
`3
`
`4
`
`5
`
`6
`
`Catchpole and
`Sampalis II
`
`Catchpole, Grynbaum
`and Randolph
`
`Catchpole and
`Enzymotec
`
`Catchpole, Enzymotec
`and Sampalis II
`
`Catchpole, Enzymotec,
`Sampalis II, Grynbaum
`and
`Randolph
`
`
`
`
`Claims
`Challenged
`1, 5-6, 11
`
`4, 7, 12-13
`
`8-10
`
`
`35 U.S.C. § 103(a)
`
`35 U.S.C. § 103(a)
`
`35 U.S.C. § 103(a)
`
`1-3, 5-6, 11
`
`35 U.S.C. § 103(a)
`
`14-16, 20
`
`35 U.S.C. § 103(a)
`
`17-19
`
`6
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`IPR2018-01730
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`‘752 Patent Independent Claims Summary
`
`
`
`U.S. Patent No. 9,072,752
`
`
`
`7.
`
`A summary chart of the ‘752 Patent’s Independent Claims is included
`
`below for reference.
`
`
`
`
`
`
`
`
`
`
`
`
`
`‘752 Patent Claim 1
`
`A polar krill oil comprising
`
`
`greater than about 40%
`phosphatidylcholine w/w of said krill
`oil and
`
`greater than about 5% ether
`phospholipids w/w of said krill oil.
`
`‘752 Patent Claim 14
`
`A Euphausia superba krill oil
`comprising
`
`greater than about 45%
`phosphatidylcholine w/w of said krill
`oil,
`
`greater than about 5% ether
`phospholipids w/w of said krill oil,
`
`less than about 25% triglycerides w/w
`of said krill oil,
`
`at least 36% omega-3 fatty acids w/w
`of said krill oil, and
`astaxanthin.
`
`
`
`7
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`RIMFROST EXHIBIT 1086 Page 0011
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`IPR2018-01730
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`
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`‘752 Patent Amended Claims Invalidity Grounds
`
`
`
`U.S. Patent No. 9,072,752
`
`
`
`8.
`
`A summary chart of the ‘752 Patent Amended Claims Invalidity
`
`Grounds is included below for reference.
`
`
`35 U.S.C.
`§ 103(a)
`
`
`22(2), 23(3), 25(11),
`28(14), 29(20)
`
`
`35 U.S.C.
`§ 103(a)
`
`
`21(1), 22(2), 23(3), 24(4),
`25(11), 26(12), 27(13)
`28(14), 29(20)
`
`8
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`RIMFROST EXHIBIT 1086 Page 0012
`
`
`Catchpole, NKO
`(AAPA), Sampalis II
`and Randolph
`
`
`Catchpole, Enzymotec,
`NKO (AAPA),
`Sampalis II and
`Randolph
`
`
`Catchpole, Enzymotec,
`NKO (AAPA),
`Sampalis II and
`Randolph
`
`
`
`
` 7
`
`
`
` 8
`
`
`
` 9
`
`
`
`
`
`
`
`
`
`Ground
`
`
`Reference(s)
`
`Basis
`
`Amended Claims
`Challenged
`(Original Claims)
`
`
`21(1), 24(4), 25(11),
`26(12), 27(13)
`
`
`35 U.S.C.
`§ 103(a)
`
`

`

`IPR2018-01730
`
`
`
`‘752 Patent Amended Independent Claims Summary
`
`
`
`U.S. Patent No. 9,072,752
`
`9.
`
`A summary chart of the ‘752 Patent’s Amended Independent Claims
`
`is included below for reference.
`
`
`
`
`
`
`
`
`
`
`‘752 Patent Amended Claim 21(1)
`
`A polar krill oil comprising
`
`greater than about 40%
`phosphatidylcholine w/w of said krill
`oil,
`
`
`and greater than about 5%
`
`from 6% to 10% ether phospholipids
`w/w of said krill oil,
`
`
`
`
`
`
`
`and from 100 to 700 mg/kg astaxanthin
`esters.
`
`‘752 Patent Amended Claim 28(14)
`
`A Euphausia superba krill oil
`comprising
`
`greater than about 45%
`phosphatidylcholine w/w of said krill
`oil,
`
`greater than about 5%
`
` from 6% to 10% ether phospholipids
`w/w of said krill oil,
`
`less than about 25% triglycerides w/w
`of said krill oil,
`
`at least 36% omega-3 fatty acids w/w
`of said krill oil, and
`
`from 100 to 700 mg/kg astaxanthin
`esters astaxanthin.
`
`
`
`
`9
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`RIMFROST EXHIBIT 1086 Page 0013
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`IPR2018-01730
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`
`U.S. Patent No. 9,072,752
`
`
`
`IV. PATENT OWNER’S VALIDITY ARGUMENTS FAIL
`
`10. Patent Owner (“PO”) asserts several arguments in PO’s Response to
`
`Petition (POR1730) and in PO’s Motion to Amend (POMTA1730) as to why its
`
`‘752 Patent claims and proposed amended claims should not be found to be
`
`obvious. Patent Owner’s arguments are wrong.
`
`
`
`A. First, PO argues that none of the references, including Catchpole (Exhibit
`1009) disclose krill oil with greater than 5%, 6%, 7% and from 6% to 10%
`(in the amended claims) ether phospholipids - PO is wrong.
`
`
`11. PO wrongly argues that none of the references, including Catchpole
`
`(Exhibit 1009) disclose krill oil with greater than 5%, 6%, 7% and from 6% to 10%
`
`(in the amended claims) ether phospholipids. See, for example, POR, pp. 4-5, 15-
`
`22, Paper 13; POMTA, pp. 11-16, Paper 12; Hoem Dec. ¶¶ 52-65, 74-79, 87-96,
`
`98-105, 107-109.
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`12.
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`I disagree. For one thing, Catchpole by itself in a single reference
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`discloses to a POSITA greater than 5%, 6%, and 7% and from 6% to 10% (in the
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`amended claims) ether phospholipids by weight in krill oil; and discloses how to
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`obtain these levels with a high expectation of predictability and success in doing
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`so.
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`13.
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`I note that Catchpole expressly discloses krill as the preferred feed
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`material for making a phospholipid extract with high concentrations of PC and
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`AAPC.
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`14.
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`I further note that Catchpole not only expressly discloses that the
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`purpose of the invention is to make a product that comprises greater than 5%, and
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`greater than 10%, alklyacylphospholipids; but also provides both the motivation
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`and the methods required to prepare such a krill oil. All of these points are detailed
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`as follows:
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`Catchpole discloses expressly in an example: (a) a krill feed material
`containing 0.7 wt% ether phospholipids, (b) a krill oil extracted from the krill
`feed material containing at least 4.8 wt% ether phospholipids, and (c) methods
`for producing said krill oil.
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`15. Catchpole discloses in Example 18, the composition of major
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`phospholipids in a feed material (freeze dried krill meal) in Table 16, comprising
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`the ether phospholipids 0.6 wt% AAPC and 0.1 wt% AAPE, to give a total
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`disclosed ether phospholipid content of 0.7 wt% in the freeze dried krill meal, and
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`a total of all of the disclosed phospholipids of 7.8 wt%. See Catchpole, Table 16,
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`Exhibit 1009, p. 0024.
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`16. Catchpole further discloses in Example 18, a krill oil extracted from
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`the feed material that contains at least 4.8 wt% alkylacylphospholipid. This is
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`acknowledged and undisputed by PO. See, e.g., Hoem Dec. ¶¶ 47, 64, 74, Exhibit
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`2001. Table 16 shows the composition of an extract, ‘extract 2’, that has been
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`produced by first extracting some of the neutral lipids from a freeze dried krill
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`meal using CO2 only, followed by extraction of the remaining krill meal using CO2
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`and 11% ethanol co-solvent at 300 bar and 313K (40°C). The composition of the
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`extract (extract 2) is described in Example 18 as containing at least 4.8 wt%
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`alkylacylphospholipids (4.6% AAPC, an alkylacylphospholipid, plus 0.2% AAPE,
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`another alkylacylphospholipid = 4.8 wt%. This is the same as greater than about 5
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`wt%, which in my interpretation includes at least greater than 4.5%, and certainly
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`greater than 4.8%. Other minor ether phospholipids, such as LAAPC, were not
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`specifically disclosed but were also known to be present). See Catchpole, 24:1-16
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`& Table 16, Exhibit 1009, p. 0024. See also discussion below where the expected
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`presence of lyso-phospholipids, as acknowledged by PO, would be expected to
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`make the ether phospholipid content in Catchpole’s Example 18 krill oil expressly
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`greater than 5 wt %.
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`17. Catchpole still further discloses in Example 18, a residual material
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`(Residue), after the two extraction stages. It is described in Table 16, as containing
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`0.5 wt% AAPC and 0.1 wt% AAPE, to give a total disclosed ether phospholipid
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`content of 0.6 wt% and a total of all the disclosed phospholipids of 4.7 wt%.
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`Catchpole, Table 16, Exhibit 1009, p. 0024.
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`Catchpole discloses that krill meal is a preferred substrate for producing a krill
`oil with the claimed ether phospholipids levels of greater than 5%, greater than
`10%, and even higher.
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`18. PO argues that Catchpole does not disclose that greater than 5% and
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`greater than 10% ether phospholipids can be made from krill because, in the words
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`of Dr. Hoem, “…Catchpole teaches that the suitable source materials are virtually
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`unlimited”. Hoem Dec. ¶ 90, Exhibit 2001. I disagree. Catchpole discloses
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`expressly the type of feed material that should be used for preparing the products
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`of the invention, including products with enriched ether phospholipid content.
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`Catchpole discloses in general that the feed material may be derived from
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`“terrestrial animals, marine animals, terrestrial plants, marine plants, or micro-
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`organisms such as microalgae, yeast and bacteria. Preferably the feed material is
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`derived from sheep, goat, pig, mouse, water buffalo, camel, yak, horse, donkey,
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`llama, bovine or human.” Catchpole, 7:5-9, Exhibit 1009, p. 0007.
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`19. More specifically, however, Catchpole discloses that the feed material
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`must include at least one of the desired compounds to be concentrated (see for
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`example, Abstract (57), Catchpole, p. 0000), and, for acylalkylphospholipids (ether
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`PL) specifically, Catchpole specifies that the feed material comprises at least 0.3%
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`by mass acylalkylphospholipids. “[W]herein the feed material comprises …, at
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`least 0.3% by mass acylalkylphospholipids and/or plasmalogens, …”. Abstract
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`(57), Catchpole, Exhibit 1009, p.0000; see also Summary of the Invention,
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`Catchpole, at 4:7 (0.3%), 5:7 (0.5%), 5:20, 6:24 (0.5%), pp. 0004-0006; and in the
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`Claims, Catchpole, at 27:8 (0.3%), 28:16-21 (0.3%, 0.5%, 2%, and 10%), 29:6
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`(0.3%), pp. 0027-0029.
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`20. Catchpole further discloses that is it is even more preferable to have
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`even higher levels of ether PL in the feed material. “Alternatively the feed material
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`comprises greater than 0.5% acylalkyphospholipids and/or plasmalogens. More
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`preferably the feed material comprises greater than 2% acylalkyphospholipids
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`and/or plasmalogens. Most preferably the feed material comprises greater than
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`10% acylalkyphospholipids and/or plasmalogens.” Summary of the Invention,
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`Catchpole, Exhibit 1009, 5:7-10, p. 0005 and elsewhere.
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`21.
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`It would also be an obvious matter of fact to a POSITA that a
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`necessary component of the invention of Catchpole is that the feed material must
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`contain at least some, and preferably an elevated level, of the compounds that are
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`to be concentrated.
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`22. Because the invention of Catchpole relates to a process “for separating
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`a feed material into soluble and insoluble components” (Abstract (57), Catchpole,
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`Exhibit 1009, p. 0000) then the feed material must contain at least some of the
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`phospholipid compounds that are the disclosed targets of the invention. If the
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`desired phospholipid of the invention is not present in the feed material then it
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`could not be present in either the soluble or insoluble fraction that the feed material
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`is separated into. Similarly, very low levels of the desired phospholipid in the feed
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`material will make the separation and concentration of the phospholipid more
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`difficult to achieve and possibly uneconomic.
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`23. Thus, a POSITA would understand that, for example, when Catchpole
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`refers to a preferred product of the invention that contains levels of >5wt% and
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`>10wt% ether phospholipids, Catchpole is referring to a product made from a feed
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`material that comprises at least in part some ether PL. Specific to this requirement
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`Catchpole describes that the preferred starting material contain, in part, “at least
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`0.3 % by mass acylalkylphospholipids” (Abstract (57), Catchpole, Exhibit 1009, p.
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`0000, and elsewhere), or levels that are even higher such as 0.5%, 2% or even 10%
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`(see, Catchpole, Exhibit 1009, 5:7-10, p. 0005).
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`24. Catchpole discloses specifically that several feed materials contain
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`ether PL and thus would be suitable feed materials for making the ether PL
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`enriched products of the invention. These include Examples 12, 17 and 18. None
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`of the other Examples of feed material disclose a feed material with an ether PL
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`content. See Hoem Dep., 72:3-84:22, Exhibit 1145.
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`25.
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`In Example 12 (Catchpole, Exhibit 1009, 20:18-21-3 including Table
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`11, pp. 0020-0021), the feed material was a lipid extract from Hoki Head with a
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`listed AAPC (alkylacylphosphatidylcholine, an ether phospholipid) content of 1.1
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`wt% (Table 11, row labelled ‘feed’, column AAPC). Catchpole reports that the
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`AAPC content in the extract is 1.6 wt%, and in the residue after extraction 0.0
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`wt%. Catchpole further describes that “The alkylacylphosphatidylcholine (AAPC),
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`a type of alkylacylphospholipid (ether phospholipid), is completely extracted” (id.,
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`20:27-28, p. 0020).
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`26.
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`In Example 17, “Fractionation of green-lipped mussel lipid extract”,
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`the feed material is reported to contain 0.8 wt% AAPC (Catchpole, Example 17,
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`23:14-26 and Table 15, row ‘Feed’, column ‘AAPC’). In this case the
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`alkylacylphosphatidylcholine (AAPC), again a type of alkylacylphospholipid is
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`described as partially extracted (id., 23:24-26, p. 0023).
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`27. Example 18 contains the specific disclosure of extraction of a krill
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`meal that contains 0.7 wt% alkylacylphospholipids to produce an extract 2
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`containing disclosed alkylacylphospholipids of 4.8 wt% (see above and Catchpole,
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`Example 18, 24:1-16 and Table 16, p. 0024).
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`28. All of these examples are marine feed materials. See, e.g., Hoem Dep.,
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`84:4-8, Exhibit 1145. These disclosures by Catchpole are consistent with the
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`requirement that the feed material contains at least some alkylacylphospholipids
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`and, as disclosed by Catchpole throughout the specification and the claims, are
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`consistent with the preferred levels of greater than 0.3 wt %
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`alkylacylphospholipids. Thus, Catchpole discloses that the feed material for
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`producing the products with the claimed >5% and >10% ether PL content are
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`marine animals including krill.
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`29. Of the feed materials disclosed by Catchpole the krill meal of
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`Example 18 (krill) contains 0.7% ether phospholipids, greater than the 0.3% and
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`0.5% preferred by Catchpole, further supporting the disclosure of krill meal as a
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`suitable feed source for achieving the >5%, >10%, and higher levels of ether
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`phospholipids, that are claimed in the invention.
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`30. Of the feed materials and specific examples disclosed by Catchpole,
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`the extract (Extract 2) of the krill meal of Example 18 (krill) contains the highest
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`level of ether phospholipids (AAPC (4.6%) + AAPE (0.2%) = 4.8%), further
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`supporting the disclosure of krill meal as a preferred feed source for achieving the
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`>5%, >10%, and higher levels of ether phospholipids, that are claimed in the
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`invention.1
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`31. Moreover, based on Catchpole’s disclosures, a POSITA would have
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`looked at krill oil Catchpole’s Example 18, Extract 2 as an about 5% ether
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`1 Catchpole’s krill extract 2 also has the highest concentration of phospholipids in a
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`feed with ether phospholipids, and as POSITA was also motivated to achieve
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`higher concentrations of phospholipids in its extracts, this would motivate POSITA
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`to use krill as its source material as well.
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`phospholipid “feed” source for further extraction and concentration of ether
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`phospholipids and thus as another preferred feed source for achieving the >5%,
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`>10%, and higher levels of ether phospholipids, that are claimed in the invention.
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`32.
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`In addition to the necessary inclusion of ether phospholipid content in
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`the feed material, Catchpole further describes the general properties of a feed
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`material that is suitable for making the products of the invention: “It is
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`advantageous to start with a feed material containing at least 5% by mass of lipids,
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`and ideally at least 2% by mass of phospholipids, particularly PS, SM, CL, ALP
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`[alkylacylphospholipid or ether phospholipid], PL, PP, CAEP and/or
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`gangliosides.” Catchpole, 11:19-21, Exhibit 1009, p. 0011. Krill meal, disclosed in
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`Example 18, meets all of these criteria – namely a lipid content of 21.4% by mass
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`(id., 24:4,