Ex Parte Raa et alDownload PDFPatent Trials and Appeals BoardApr 30, 201914141492 - (D) (P.T.A.B. Apr. 30, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/141,492 12/27/2013 29078 7590 CHRISTIAN D. ABEL Onsagers AS Munkedamsveien 35 P.O. Box 1813 Vika Oslo, N-0123 NORWAY 05/02/2019 FIRST NAMED INVENTOR Jan Raa UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www .uspto.gov ATTORNEY DOCKET NO. CONFIRMATION NO. P22027USPC01 9817 EXAMINER YU,HONG ART UNIT PAPER NUMBER 1612 NOTIFICATION DATE DELIVERY MODE 05/02/2019 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): post@onsagers.no christian.abel@onsagers.no cdabell 14@gmail.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JAN RAA, GUNNAR RORSTAD, and KURT STEINAR TANDE 1 Appeal2018-000187 Application 14/141,492 Technology Center 1600 Before RICHARD M. LEBOVITZ, TA WEN CHANG, and RYAN H. FLAX, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method for reducing the risk of contracting obesity and type-2 diabetes or treatment of abdominal obesity and type 2 diabetes, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We REVERSE. STATEMENT OF THE CASE According to the Specification, "[t]he present invention concerns an oil composition, particularly an oil composition that reduces accumulation of 1 Appellants identify the Real Party in Interest as Calanus AS. (Br. 1.) Appeal2018-000187 Application 14/141,492 visceral fat in the body and improves glucose tolerance and hence may be used to prevent or treat obesity related diseases," which is derived from the marine copepod Calanusfinmarchicus. (Spec. 1:10-12, 6:19-20.) The Specification states that the oil from Cal anus finmarchicus is rich in wax esters, which are "esters of long-chain or very long-chain acids (fatty acids) and long-chain or very long-chain alcohols (fatty alcohols)." (Id. at 5:28- 29, 7:19-21.) Further according to the Specification, although "[t]he oil composition of the present invention contains n-3 fatty acids EPA ... and DHA," which are known to inhibit diet-induced visceral obesity (id. at 3: 17- 4:8, 7: 11-13), "it is a common understanding among the skilled in the field that wax esters are not digestible, and that a marine wax ester rich oil like that from Cal anus finmarchicus therefore is a poor source of EPA and DHA." (Id. at 7:19-21.) Claims 1--4, 6-9, and 11-13 are on appeal. Claim 1 is illustrative and reproduced below: 1. A method for reducing the risk of contracting obesity and type-2 diabetes or treatment of abdominal obesity and type 2 diabetes comprising administering to a patient in need thereof a clinically effective dosage of a composition comprising 20-100 % by weight of wax esters isolated from a copepod of the genus Cal anus, wherein said wax esters consist of monoesters of mono- or polyunsaturated C 16 to C22 fatty acids and monounsaturated C 16 to C22 fatty alcohols, and wherein said fatty acids are comprised of 5-20% by weight of stearidonic acid (SDA). (Br. 18 (Claims App'x).) 2 Appeal2018-000187 Application 14/141,492 The Examiner rejects claims 1--4, 6, 7, 9, and 11-13 under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Holmeide, 2 Horrobin, 3 and Kattner. 4 (Final Act. 3.) The Examiner rejects claim 8 under pre-AIA 35 U.S.C. § I03(a) as being unpatentable over Holmeide, Horrobin, Kattner, and Bruheim. 5 (Final Act. 10.) DISCUSSION Issue The Examiner has rejected claims 1--4, 6, 7, 9, and 11-13 as obvious over Holmeide, Horrobin, and Kattner. The Examiner rejects claim 8 under pre-AIA 35 U.S.C. § I03(a) as being unpatentable over Holmeide, Horrobin, Kattner, and Bruheim. The same issues are dispositive for both rejections; we, therefore, discuss them together. The Examiner finds that Holmeide teaches a method of treating type-2 diabetes, obesity, and weight gain comprising administering a composition comprising at least 60% by weight of a co-3 lipid compound of formula (I): 2 Holmeide et al., WO 2008/132552 A2, published Nov. 6, 2008 ("Holmeide"). 3 Horrobin, US 2002/0025983 Al, published Feb. 28, 2002. 4 G. Kattner & M. Krause, Changes in Lipids During the Development of Calanus finmarchicus s.l.from Copepodid I to Adult, 96 MARINE BIOLOGY 511 (1987) ("Kattner"). 5 Bruheim et al., US 2008/0274203 Al, published Nov. 6, 2008 ("Bruheim"). 3 Appeal2018-000187 Application 14/141,492 R, R2 . .(P . d) wherein R1 may be H, R2 maybe --CH3, Y may be a C14--C22 alkenyl and P may be wherein P1 and P2 may be Hand P3 may be a C14--C22 alkenyl group having at least one double bond. (Final Act. 5.) The Examiner finds that such a compound would be a wax ester comprising a C17--C2s mono-unsaturated fatty alcohol and a C1s--C23 mono- and/or poly-unsaturated fatty acid, similar to that recited in claim 1. (Final Act. 5.) In light of the above, the Examiner finds that Holmeide suggests most of the limitations of claim 1, except that Holmeide does not teach isolating the wax ester from a copepod of the genus Cal anus and also does not explicitly teach that the C1s--C23 mono- and/or poly-unsaturated fatty acid comprises 5-20% by weight of SDA. (Id. at 6.) The Examiner finds, however, that Horrobin teaches a composition for treating diabetes and obesity comprising more than 1 % by weight of SDA. The Examiner also finds that Kattner teaches extracts from Cal anus finmarchicus comprising 85% and at least 50% by weight of wax ester in spring and winter, respectively. (Id. at 6-7.) 4 Appeal2018-000187 Application 14/141,492 The Examiner concludes that it would have been obvious to a skilled artisan to modify Holmeide' s composition to include more than 1 % by weight of SDA, with a reasonable expectation of success, because Horrobin teaches using compositions comprising more than 1 % SDA to treat diabetes and obesity. (Id. at 7.) The Examiner further concludes that it would have been obvious to a skilled artisan to use Kattner's wax esters extracted from Cal anus finmarchicus in place of Holmeide' s synthetic wax ester, because "[i]t is prima facie obvious to select a known material for incorporation into a composition[] based on its recognized suitability for its intended use." (Id. at 10.) Finally, with respect to claim 8, which depends from claim 1 and further recites "administering to a patient in need thereof a clinically effective dosage of [a] composition containing 500-4000 ppm of astaxanthin," the Examiner cites Bruheim for teaching "treating type-2 diabetes and obesity (including abdominal obesity) with krill oil comprising 500 ppm [ ofJ a strong antioxidant astaxanthin." (Br. 19 ( Claims App 'x ); Final Act. 11.) The Examiner finds that doing so would have been obvious. Appellants contend that Holmeide teaches a synthetic compound, rather than a compound derived from a copepod of the genus Calanus. (Br. 11.) Appellants contend that Holmeide's compound is a "2-substituted QQ.lyunsaturated omega-3 alcohol," rather than a monosaturated fatty alcohol as required by claim 1. (Id.) Appellants contend that Holmeide teaches that the 2-substitution is essential for the pharmaceutical efficacy of its compound, whereas the naturally synthesized wax esters of the claims "have no substituents anywhere in the carbon chain of the fatty acids or fatty alcohols." (Id. at 11-16.) Appellants thus contend that, not only does 5 Appeal2018-000187 Application 14/141,492 Holmeide not teach the claimed wax ester, Holmeide in fact teaches away from it. 6 (Id.) Finally, Appellants contend that Holmeide does not provide any evidence or data to support the asserted pharmaceutical effect of its compound and is not enabled. (Id. at 12, 15-16.) With respect to the combination with Horrobin, Appellants contend that Horrobin does not cure Holmeide's deficiency in failing to teach SDA, because the claims relate to SD As that are part of wax esters while the SDA taught by Horrobin is a free fatty acid. (Id. at 14.) With respect to the combination with Kattner, Appellants contend that "there is nothing in Kattner ... that indicate[ s] the therapeutic effect of the wax esters of Calanus." (Id.) The issue with respect to these rejections is whether a preponderance of the evidence of record supports the Examiner's conclusion that the cited combination of prior art suggest the method of claim 1. Findings of Fact 1. Holmeide teaches that 6 In support of their arguments that Holmeide does not teach the compounds of claim 1 and that modifying Holmeide's compound to include the limitation of claim 1 would render it unsuitable for its intended purpose, Appellants cite Johanne Dalsgaard et al., Fatty Acid Trophic Markers in the Pelagic Marine Environment, in ADVANCES IN MARINE BIOLOGY 225 (Southward et al. eds., 2003) ("Dalsgaard"); Martin Graeve et al., Assimilation and Biosynthesis of Lipids in Arctic Calanus Species Based on Feedings Experiments with a 13C Labelled Diatom, 317 J. EXPERIMENTAL MARINE BIOLOGY AND ECOLOGY 109 (2005) ("Graeve"); John R. Sargent et al., Marine Wax Esters, in CHEMISTRY AND BIOCHEMISTRY OF NATURAL WAXES 50 (Kolattukudy ed., 1976) ("Sargent"); STEPHEN M. MUDGE, FATTY ALCOHOLS-A REVIEW OF THEIR NATURAL SYNTHESIS AND ENVIRONMENTAL DISTRIBUTION (2005) ("Mudge"); and the Declaration of Ragnar L. Olsen under Rule 1.132 (Mar. 15, 2016) ("Olsen Deel."). 6 Appeal2018-000187 Application 14/141,492 [t]he regulation of gene transcription by [polyunsaturated fatty acids (PUP As)] has profound effects on cell and tissue metabolism and offers a credible explanation for the involvement of nutrient-gene interactions in the initiation and prevention or amelioration of diseases such as obesity, diabetes, cardiovascular disorders, immune-inflammatory disease and cancers. Fish oils rich in the co-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce the risk of cardiovascular diseases partly by reduction of blood triglyceride concentration. This favorable effect mainly results from the combined effects of inhibition of lipogenesis by decrease of SPEBP-I and stimulation of fatty acid oxidation by activation of [proliferators-activated receptors (PPAR)]-a in the liver. (Holmeide ,r 3 (citation omitted).) 2. Holmeide teaches that [ t ]he carboxylic acid functional group of the PUP As is important to target binding in the PP ARs, but this ionizable group may hinder the drug from crossing the cell membranes of the gut wall. Accordingly, carboxylic acids functional groups in drugs are often protected as an ester. The less polar ester group can cross the fatty cell membranes, and once in the bloodstream it can be hydrolyzed back to the free acid by esterases in the blood. It is also possible that plasma enzymes do not hydrolyze these esters fast enough and that the conversion of ester to free acid predominantly takes place downstream in liver. The same occurs for ethyl esters of polyunsaturated fatty acids that are hydrolyzed to a free acid in vivo. (Id. ,I,I 26-27.) 3. Holmeide teaches that, "[ d]ue to their limited stability in vivo and their lack of biological specificity, PUFAs have not achieved widespread use as therapeutic agents. Chemical modifications of the n-3 7 Appeal2018-000187 Application 14/141,492 polyunsaturated fatty acids have been performed by several research groups in order to change or increase their metabolic effects." (Id. ,r 4.) 4. Holmeide teaches that "introduction of a substituent in the a- position of polyunsaturated fatty acids increase their affinities to nuclear receptors and, in particular, to the PPARs." (Id. ,r 25 (italics removed).) Holmeide further teaches that, "[b ]ecause 2-substituted polyunsaturated fatty acid derivatives have the potential of being used for therapeutic purposes, compounds according to the present invention are novel pro-drugs of a- substituted fatty acids. These pro-drugs may have improved therapeutically activity, increased bioavailability and ability to cross the cell membrane." (Id. ,I 28.) 5. Holmeide teaches 2-substituted "omega-3 lipid compounds having pharmaceutical activity" and of formula (I): wherein R[lJ and R2 are the same or different and are chosen from a hydrogen atom, a hydroxyl group, an alkyl group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkenyl group, an alkynyl group, an aryl group, an alkylthio group, an alkoxycarbonyl group, a carboxy group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group, and an alkylamino group; P represents a hydrogen atom, or P represents 8 Appeal2018-000187 Application 14/141,492 wherein P1, P2, and P3 are chosen from a hydrogen atom, an alkyl group, and a C14-[C22] alkenyl group, wherein the alkyl and alkenyl groups are optionally substituted with a hydroxyl group, or P represents[:] 0 ~ H -,,.--5----0H <:: ·:< n 0 or P represents[:] 0 , !I '"~-P-OH ~ l OH P represents[:] or ; or :. and Y is a C14-C22 alkenyl group with at least one double bond, having E and/or Z configuration; or any pharmaceutically acceptable complex, solvate, salt or pro-drug thereof, with the proviso that R1 and R1 are not simultaneously a hydrogen atom. 9 Appeal2018-000187 Application 14/141,492 (Id. ,r,r 7-8, 37 (italics removed), 38.) 6. Holmeide teaches exemplary embodiments including wax esters: 0 ; and (Id. ,r 9; see also id. ,r,r 39, 94.) 7. Holmeide teaches a composition comprising an omego-3 liquid compound according to formula (I) where the compound is present in a concentration of at least 60% by weight. (Id. ,r 21.) 8. Holmeide teaches "the use of an omega-3 lipid compound according to formula (I) for the production of a medicament for the following: ... the treatment and/or the prevention of type 2 diabetes[,] ... the treatment and/or prevention of obesity or an overweight condition" as well as "methods for the treatment and/or prevention of the conditions listed above, comprising administering to a mammal in need thereof a pharmaceutically active amount of a compound according to formula (I)." (Id. ,I,I 22-23, 103-104.) 9. Horrobin teaches "[ n ]utritional and pharmaceutical formulations comprising in combination vitamin K and a source of at least one essential fatty acid (EPA) as the essential ingredients." (Horrobin Abstract.) 10 Appeal2018-000187 Application 14/141,492 10. Horrobin teaches that there are two types ofEPAs: "the omega-6 derived from the parent linoleic acid, and the omega-3 derived from the parent alphalinolenic acid." (Id. ,r 9.) 11. Horrobin teaches that stearidonic acid is an omega-3 EPA. (Id. ,r 15.) 12. Horrobin teaches that low levels ofEPAs have been found in patients with diseases such as, e.g., diabetes. (Id. f 10.) Horrobin teaches that its formulations may be used to treat or prevent a variety of disease or conditions, including "metabolic or cardiovascular disorders including diabetes, obesity, elevated blood cholesterol or triglyceride levels or cardiovascular disorders." (Id. ,r 23; see also id. at claims 22, 31, and 39 (method of treating or preventing disease including diabetes and obesity using formulations comprising vitamin K and a source of at least one essential fatty acid or foodstuff which already contain EP As to which vitamin K is added) and claims 27, 35, and 36 (EPA selected from EPAs including stearidonic acid).) 13. Horrobin teaches that "[t]he EPAs can be in any chemical form which is absorbed into the body and incorporated into body lipids," including but not limited to "free acids, sodium, potassium, lithium and other salts, triglycerides and other glycerides, cholesterol, ethyl, methyl and other esters, amides, and phospholipids." (Id. ,r 29.) 14. Horrobin teaches examples of "500 mg or 100 mg hard or soft gelatin capsules where the natural oil contains stearidonic acid (SA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DP A), docosahexaenoic acid (DHA), dihomogammalinolenic acid (DGLA) or arachidonic acid (AA)." (Id. ,r 32; see also id. ,r,r 35-39 (example of natural 11 Appeal2018-000187 Application 14/141,492 oils containing SA), ,r 40 ( example of"[ m Jilk or milk products ... to which are added ... one or more fatty acids selected from GLA, DGLA, AA, SA, EPA, DP A and DHA, to raise the concentration of each selected fatty acid to more than 100 mg/lOOg and preferably to more than 1000 mg/100 g").) 15. Horrobin teaches that its formulation preferably comprises between 50 mg and 100 g of the EPA. (Id. ,r 12; see also id. at claim 32.) 16. Kattner teaches that Cal anus finmarchicus contains lipids and wax esters, that "[t[he wax ester proportion reached about 90% of total lipids in males and Copepodid V and up to 40% in Copepodid I," that "[t]he major fatty acids were 16:0, 20:5, and 22:6," and that "the major fatty alcohols were 16:0, 20:1 and 22:1." (Kattner Abstract.) 17. Kattner Fig. 2 is reproduced below: 12 Appeal2018-000187 Application 14/141,492 COi'EPOD ms ANO AOUL rs (Id. at 513, Fig. 2.) Figure 2 of Kattner depicts the dry weight, lipids~;; and wax ester percentage of total lipids of the copepodids and adults, wherein the letters A, B, C, and D refer to the location from which the copepods were sampled. (Id. at 513, Fig. 2 caption.) 13 Appeal2018-000187 Application 14/141,492 18. Kattner Fig. 3(a) is reproduced below: 30- 201 2J 1 10-! i o .LL.- , V lV 11 l II M F V f'< l i1 I J l M :' Y IV 11 J I J I A C D (Id. at 514, Fig. 3(a).) Figure 3(a) of Kattner depicts the fatty acid composition (%) of the copepod lipids wherein the numbers below the bars (M, F, V, IV, III, II, and I) refer to the life stage of the copepods and wherein the letters A, B, C, and D refer to the location from which the copepods were sampled. (Id. at 514, Fig. 3 caption.) 14 Appeal2018-000187 Application 14/141,492 19. Kattner Figure 3 (b) is reproduced below: r- ~' 1 V J] f I I A (Id. at 515, Fig. 3(b).) Figure 3(b) of Kattner depicts fatty alcohol composition of the copepod lipids. (Id. at 514, Fig. 3 caption.) 15 Appeal2018-000187 Application 14/141,492 Analysis On balance, we agree with Appellants that the Examiner's rejection as currently formulated does not establish a prima facie case of obviousness. In particular, although Holmeide teaches that certain wax esters (i.e., "esters of long-chain or very long-chain acids (fatty acids) and long-chain or very long-chain alcohols (fatty alcohols)" (Spec. 5:28-29, 7:19-21)) are useful in preventing or treating type-2 diabetes and obesity, the Examiner has not established that these particular wax esters can be isolated from a copepod of the genus Cal anus, or that a skilled artisan would understand from the cited references that the wax esters isolated from such copepods would perform the same function as Holmeide' s synthetic wax esters. As Appellants point out, Holmeide' s wax esters are 2-substituted. (FF5.) While Kattner teaches that Calanus finmarchicus contains significant amounts of wax esters (FF 16, FF 1 7), the Examiner has not asserted that Kattner teaches that these wax esters are 2-substituted. For this reason, the Examiner has not persuasively shown that one of ordinary skill in the art would have had reason to use Kattner's wax esters in place of the wax esters described in Holmeide, because the Examiner has not established that one of ordinary skill in the art would have reasonably expected that the structurally different esters would have the same functional properties. The Examiner asserts that Holmeide's wax esters substantially overlap with the claimed wax esters and that the claims do not exclude 2-substituted wax esters. (Ans. 3.) We are not persuaded. The relevant question is not merely whether the claims exclude Holmeide's 2-substituted wax esters, but whether a skilled artisan would have a reasonable expectation that such wax esters may or should be isolated from a copepod of the genus Cal anus, as 16 Appeal2018-000187 Application 14/141,492 required by claim 1. The Examiner has not cited to any persuasive evidence that 2-substituted wax esters would have been isolated from such copepods by the skilled artisan. Citing Mudge and an online reference, the Examiner asserts that, contrary to Appellants' argument, naturally synthesized fatty acids/fatty alcohols may be branched (i.e., may have alkyl substitution on the carbon chain) like the compounds taught in Holmeide. (Ans. 3.) We are not persuaded. The portion of Mudge cited by the Examiner states that "a range of branched chain [ fatty alcohols] are also naturally produced by micro-organisms in the environment" and that "[t]he major positions for the methyl branches are on the carbons at the opposite end of the molecule to the terminal-OH." (Mudge 5.) The Examiner does not persuasively explain how this generic teaching, or the teaching of the cited online reference, 7 would lead a skilled artisan to reasonably expect that a copepod in particular would naturally synthesize the wax esters having the specific substitution (i.e., a 2-substitution) required by Holmeide. The Examiner asserts that, because Holmeide teaches administering synthetic wax esters to treat type-2 diabetes and obesity and Kattner teaches that Cal anus finmarchicus stage V comprises large amounts of wax ester, it would have been obvious to a skilled artisan "to replace the synthetic esters (wax esters) with extract from Copepod Calanusfinmarchicus stage V," with the predictable result of preventing or treating type-2 diabetes and obesity. (Ans. 4--5.) 7 We are unable to locate the online reference cited by the Examiner at the URL provided. 17 Appeal2018-000187 Application 14/141,492 We agree that the synthetic wax esters of Holmeide appear structurally similar to the wax esters that Kattner teaches may be derived from Cal anus finmarchicus. However, the Examiner does not suggest that Holmeide teaches that all wax esters would be useful in treating type-2 diabetes and obesity. Neither does the Examiner explain how or why the structural similarities between Holmeide's wax esters and the Calanus finmarchicus wax esters is such that a skilled artisan would understand that the latter would perform similar functions as the former, particularly in view of the lack of 2-substitution which Appellants argued were involved in the pharmaceutical efficacy. For instance, Holmeide teaches that naturally available polyunsaturated fatty acids "have not achieved widespread use as therapeutic agents" due to their "limited stability in vivo and their lack of biological specificity."8 (FF3.) "[R]ejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) (quoting In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). Accordingly, we reverse the Examiner's rejection of claim 1 as obvious over Holmeide, Horrobin, and Kattner. We likewise reverse the rejections of claims 2--4, 6-9, and 11-13, which depend directly or indirectly 8 The Examiner has not made any findings that administration of the claimed composition, or of oil derived from copepod of the genus Calanus, would be obvious other than for the reasons taught in Holmeide with respect to its synthetic wax esters. Likewise, the Examiner has made no findings with respect to whether administration of oil derived from copepod of the genus Cal anus would inherently meet the limitations of the claimed composition. In the absence of these findings, we decline to make these determinations in the first instance. 18 Appeal2018-000187 Application 14/141,492 from claim 1. In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992) ("[D]ependent claims are nonobvious if the independent claims from which they depend are nonobvious."). SUMMARY For the reasons above, we reverse the Examiner's decision rejecting claims 1--4, 6-9, and 11-13. REVERSED 19 Copy with citationCopy as parenthetical citation