Ex Parte Dumesic et alDownload PDFPatent Trial and Appeal BoardMar 28, 201813918097 (P.T.A.B. Mar. 28, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/918,097 06/14/2013 60961 7590 03/30/2018 Intellectual Property Dept/Dewitt Ross & Stevens Wisconsin Alumni Research Foundation 2 East Mifflin Street, Suite #600 Madison, WI 53703-2865 James A. Dumesic 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. 09820.520-Pl30272US01 1921 EXAMINER ARIAN!, KADE ART UNIT PAPER NUMBER 1651 NOTIFICATION DATE DELIVERY MODE 03/30/2018 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): IP-DOCKET@dewittross.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JAMES A. DUMESIC, BRIAN PFLEGER, JEREMY S. LUTERBACHER, and JACQUELINE RAND 1 Appeal2017-006376 Application 13/918,097 Technology Center 1600 Before RICHARD J. SMITH, TA WEN CHANG, and RY ANH. 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 of growing a microorganism, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. STATEMENT OF THE CASE The Specification states that "[ s ]uccessful carbohydrate recovery from lignocellulosic biomass requires breaking intermolecular bonds in glucan and xylan chains while avoiding further reaction of the resulting glucose and 1 Appellants identify the Real Party in Interest as Wisconsin Alumni Research Foundation. (Appeal Br. 2.) Appeal2017-006376 Application 13/918,097 xylose." (Spec. 1:10-12.) According to the Specification, this requirement has led to reaction systems incorporating various features---e.g., short resident times at high temperatures, catalysts, thermochemical pretreatments, and/or a flow-through reaction system-that may be impractical, expensive, or otherwise disadvantageous. (Id. at 1:12-2:1S.) Further according to the Specification, the invention relates to a process of reacting biomass "to produce an aqueous solution of carbohydrates comprising C6-sugar- containing oligomers, C6-sugar monomers, CS-sugar-containing oligomers, CS-sugar monomers, or any combination thereof," which can then be incorporated into growth media for microorganisms as a source of carbon. (Id. at 3:21--4:12.) Claims 1--4, 8-12, 16, and 20-2S are on appeal. Claim 1 is illustrative and reproduced below: 1. A method of growing a microorganism, the method comprising: (a) reacting biomass or a biomass-derived reactant with a solvent system comprising (i) an organic solvent selected from the group consisting of beta- lactones, gamma-lactones, delta-lactones, and combinations thereof, and (ii) at least about 1 wt% water, in the presence of an acid catalyst for a time and under conditions to yield a product mixture wherein at least a portion of water-insoluble C6-sugar-containing polymers or oligomers, or water-insoluble CS-sugar-containing polymers or oligomers, if present in the biomass or biomass-derived reactant, are converted to water-soluble C6-sugar monomers, CS-sugar monomers, or any combination thereof; and then (b) partitioning or extracting the product mixture into an organic layer and a substantially immiscible aqueous layer, wherein the substantially immiscible aqueous layer comprises an aqueous solution of 2 Appeal2017-006376 Application 13/918,097 carbohydrates comprising C6-sugar monomers, CS-sugar monomers, or a combination thereof; and ( c) culturing the microorganism in a growth medium comprising the aqueous solution of carbohydrates. (Appeal Br. Claims App'x. 1.) The Examiner rejects claims 1--4, 8-12, 16, and 2 0-2 5 under 3 5 U.S.C. § 103 as being unpatentable over Pye,2 Petrus, 3 and Hein. 4 (Ans. 3.) DISCUSSION Issue The Examiner finds that Pye teaches a method of growing a microorganism such as E. coli, comprising treating biomass with a solvent system compnsmg organic solvents in the presence of an acid catalyst and at least 1 % water ... , forming a product mixture comprising C6-sugar monomers (monosaccharides) and organic solvent, partitioning or extracting a product mixture (black liquor) containing organic solvent and monosaccharides in a liquid fraction (aqueous solution of carbohydrates) and separating the organic solvent to obtain an aqueous solution of carbohydrates, and culturing the microorganism (sugar stream transferred to fermentation). (Final Act. 5 (citations omitted).) The Examiner finds that Pye also teaches "reducing the concentration of organic solvent in the immiscible aqueous layer (spent organic solvent is recovered from the aqueous layer)." (Id. at 6.) 2 Pye et al., US 2012/0094348 Al, published Apr. 19, 2012. 3 Petrus et al., US 2007 /0034345 Al, published Feb. 15, 2007. 4 Silke Hein et al., Biosynthesis of poly(4-hydroxybutyric acid) by recombinant strains of Escherichia coli, 153 FEMS MICROBIOLOGY LETTERS 411 (1997). 3 Appeal2017-006376 Application 13/918,097 The Examiner finds that Pye does not explicitly teach selecting the organic solvent from the group consisting of beta-lactones, gamma-lactones, delta-lactones, and combinations thereof. (Id.) However, the Examiner finds that Pye teaches that a suitable solvent can be used, while Petrus teaches (Id.) treating biomass ... with a solvent system comprising gamma- lactone (in the presence of an acid catalyst and at least 1 % water) and forming product mixture comprising C6-sugar monomers (glucose) and organic solvent, and further teach partitioning the product mixture to obtain an aqueous solution of carbohydrates comprising C6-sugar monomers (glucose). The Examiner concludes that a skilled artisan, based on Petrus' teaching that gamma-lactone was a suitable organic solvent for organosolv pulping, would have been motivated to use a gamma-lactone in Pye's method to "react the biomass with gamma-lactone[,] at least 1 wt% water[,] and in the presence of an acid catalyst, with a reasonable expectation of success in solubilizing biomass and forming a product mixture comprising water soluble C6-sugar monomers, and further partitioning the product mixture to obtain an aqueous solution of carbohydrates." (Id.) The Examiner finds that Hein would have provided a skilled artisan with additional motivation to use gamma-lactone as the organic solvent in Pye's method, because Hein teaches culturing E. coli in a growth medium comprising C6-sugar monomers (glucose) and gamma-lactone. (Id. at 6-7.) The Examiner finds that, based on such teaching from Hein, a skilled artisan would have recognized that E. coli can utilize gamma-lactone and C6-sugar monomers (glucose) as carbon source and would have been motivated to use gamma-lactone as the organic solvent in Pye's method. (Id. at 7.) 4 Appeal2017-006376 Application 13/918,097 Appellants contend that the cited prior art does not teach or suggest a method comprising "partitioning or extracting [a] product mixture into an organic layer and a substantially immiscible aqueous layer, wherein the substantially immiscible aqueous layer comprises an aqueous solution of carbohydrates comprising C6-sugar monomers, CS-sugar monomers, or a combination thereof," as recited in the claims. (Appeal Br. 7 (internal quotation marks omitted).) The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner's finding that the prior art combination suggests the step of "partitioning or extracting [the] product mixture [recited in step (a) of the claim 1] into an organic layer and a substantially immiscible aqueous layer, wherein the substantially immiscible aqueous layer comprises an aqueous solution of carbohydrates comprising C6-sugar monomers, CS-sugar monomers, or a combination thereof." Findings of Fact (FF) 1. Pye teaches [a Jn apparatus for processing sugar cane to concurrently produce sugar from cane juice, and ethanol and other co-products from bagasse, [the residue solids remaining after sugar cane is crushed and expressed sugar juice collected for further processing]. The apparatus comprises equipment for separating a cane juice stream and a fibrous bagasse from a sugar cane feed-stock, equipment for refining the cane juice, equipment for processing the fibrous bagasse for recovery therefrom of a cellulosic pulp and a liquor stream, equipment for saccharification and fermentation of the cellulosic pulp to produce a fermentation beer therefrom, and equipment for recovery of an ethanol stream from the fermentation beer. (Pye Abstract, i-f 2; see also id. i-fi-1 1, 3, 4.) s Appeal2017-006376 Application 13/918,097 2. Pye' s disclosed method for processing bagasse begins by pulping the bagasse waste materials by organosolv processes wherein the bagasse materials are commingled with suitable organic solvents, such as short-chain alcohols (e.g., methanol, ethanol, butanol, and propanol), organic acids, ketones, and mixtures, in suitable heated and pressurized vessels. (Id. i-f 5; see also id. at i-fi-115-16.) Pye teaches that, "[i]f so desired, the organic solvents may be additionally controllably acidified by the addition of an inorganic or organic acid." (Id. i-f 16.) 3. Pye teaches that during the "cooking process" described in FF2, "lignins and lignin-containing compounds contained within the bagasse solids stream will be fractionated and/or dissolved into the organic solvent" and also teaches that, in addition ... , the cooking process will release from the bagasse into the organic solvents in solute and particulate forms, monosaccharides, oligosaccharides and polysaccharides, organic acids such as acetic acid, formic acid and levulinic acids, and other organic compounds exemplified by furfural and 5- hydroxymethyl furfural (5-HMF) among others. (Id. i-f 16.) Pye teaches that "such organic solvents containing lignins, lignin- containing compounds, monosaccharides, oligosaccharides, polysaccharides, hemicelluloses and other organic compounds extracted from ... bagasse" are referred to as "black liquors" or "spent liquors." (Id.) 4. Pye teaches separating the cellulose pulp produced from bagasse from "black liquors." (Id. i-f 5.) 5. Pye teaches processing the cellulose pulp as follows: (a) optionally adjusting viscosity of cellulosic material using water or stillage (a liquid waste from ethanol distillation); 6 Appeal2017-006376 Application 13/918,097 (b) transferring the cellulosic pulp to equipment for enzymatic hydrolysis to produce sugar streams; ( c) culturing the sugar stream with suitable fermentation microorganisms, such as E. coli, to produce beers; and ( d) distill beer for separation and recovery of ethanol and stillage. (Id. at Figures 1, 2--4, i-fi-15, 15.) 6. Pye teaches that black liquors may be processed as follows: (a) optionally de-lignifying black liquor to recover novel lignin derivatives; (b) recover spent solvents from black liquor by distillation, which spent solvents can then be recharged by mixing with fresh solvents and recycled for additional organosolv pulping; ( c) optionally recover furfurals from spent organic solvent during distillation; ( d) optionally process stillages separated from the spent solvent for recovery of other extractives such as acetic acid, sugar syrups comprising, e.g., hexoses and pentoses, formic acid and levulinic acid; ( e) optionally deliver a portion of recovered sugar syrup to the fermentation equipment for increased yields of ethanol from bagasse waste materials; ( t) optionally process waste materials produced during recovery of organic acids and sugar syrups from stillage to collect biogas, water, and mineral solids. (Id. at Figures 1, 2--4, i-fi-16, 16-17, 20.) 7. Petrus teaches that, 7 Appeal2017-006376 Application 13/918,097 [i]n organosolv pulping, lignocellulosic material is heated in a solvent comprising organic compounds and optionally water, in order to dissolve the greater part of the hemicellulose and lignin and to obtain a high-quality, high-molecular weight cellulose that is suitable for paper production. The solvent is separated from the dissolved hemicellulose and lignin by simple distillation for recycling. (Petrus i-f 3 . ) 8. Petrus teaches that "[o]ften water is part of the solvent, typically in an amount up to 50 wt %" and that "[a] small amount of strong mineral acid ... may be added as catalyst to the solvent." (Id. i-f 4.) 9. Petrus teaches "a process for organosolv pulping, wherein solid lignocellulosic feed material is heated ... in a solvent to obtain a solid cellulosic fraction ... and a liquid fraction," wherein the solvent comprises compounds having a gamma lactone group. (Id. at Abstract, i-fi-17-8, 16.) 10. Petrus teaches that the lignocellulosic feed material may be any lignocellulosic material known to be a suitable feedstock for pulping process," including bagasse. (Id. if 20.) 11. Petrus teaches that the solvent (i.e., the total liquid phase in which the solid feed material is heated) in its process may also comprise "organic compounds that are known solvents for organosolv pulping," including lower aliphatic alcohols such as methanol or ethanol, as well as water, preferably in an amount up to 50 wt%, more preferably up to 20 wt %, and an acid catalyst. (Id. i-fi-1 17-18.) 12. Petrus teaches that the liquid fraction from organosolv pulping "contains the solvent and dissolved hemicellulose and lignin degradation products." (Id. i-f 12.) 8 Appeal2017-006376 Application 13/918,097 13. Petrus teaches that preferably the gamma lactone compounds used in the solvent are recovered for recycling, including for instance by the following process: (a) separating the solid cellulose fraction from the liquid fraction; (b) adding water to the separated liquid fraction and heating the separated liquid fraction in the presence of an acid catalyst at a temperature in the range of from 100 to 3 00° C. to obtain a hydrolysed liquid fraction; ( c) distilling lower boiling compounds in the hydrolysed liquid fraction from the [gamma lactone] compound ... ; and ( d) using the [gamma lactone] compound ... obtained in step ( c) in the solvent wherein the feed material is heated. (Id. ifif 28-32.) 14. Petrus teaches that advantages of using its gamma lactones as a solvent in organosolv pulping include: (a) they have a relatively high boiling point such that organosolv pulping can be carried out at a relatively low pressure; (b) they are both polar and relatively inert and thus act as effective organosolv solvent that "hardly form reaction products with the lignocellulosic feed material or with components formed during the organosolv process"; and ( c) the solvent may be recycled by distilling the hydrolyzed dissolved feedstock degradation products from the solvent due to the solvent's relatively high boiling temperature, which requires a smaller distillation capacity than the converse situation (i.e., when a solvent having a lower boiling point has to be distilled from the feed degradation products). (Id. ifif 10-11.) 15. Hein relates to the production of the homopolyester poly( 4- hydroxybutyric acid) (poly(4HB)) with recombinant strains of E.coli. (Hein Abstract.) 9 Appeal2017-006376 Application 13/918,097 16. Hein teaches that its recombinant strains of E. Coli synthesized poly(4HB) when "cells were cultivated in Luria-Bertani broth and if glucose and 4-hydroxybutyric acid were provided as carbon sources." (Id.) Hein teaches that "the addition of 4-hydroxy-butyric acid to the medium as a carbon source was essential to obtain [polyhydroxyalkanoic acids (PHA)] containing 4HB, and glucose provided as a cosubstrate appeared to limit the incorporation of 3HB into PHA." (Id. at 414, left column; see also id. at 415 (Table 1), 416 (Table 2).) 1 7. Hein teaches that "4 HB was also incorporated into PHA if y- butyrolactone was used as a carbon source. If levulinic acid, 4- hydroxyvaleric acid or y -valerolactone were used as carbon sources, only very low amounts of PHA were accumulated which did not contain 4- hydroxyalkanoic acids as constituents." (Id. at Abstract; see also id. at 416, right column--417, Table 3.) 18. Hein teaches that since y-butyrolactone is much cheaper than 4 HB, it provides an advantage for the production of 4-HB containing PHA. (Id. at 418, left column.) Analysis We agree with the Examiner that claim 1 would have been obvious over the combination of Pye and Petrus. See generally In re Bush, 296 F .2d 491, 496 ( CCP A 1961) (the Board may rely on less than all of the references relied upon by Examiner). Pye teaches fermentation (i.e., "a method of growing a micro- organism") using sugar stream and sugar syrup obtained from organosolv pulping of sugar cane bagasse. (FFl, FF5, FF6.) Pye teaches that its 10 Appeal2017-006376 Application 13/918,097 process comprises reacting the bagasse (i.e., "biomass") with a solvent system comprising organic solvents such as methanol and ethanol and an acid. (FF2.) Pye teaches that the organosolv process release mono saccharides from the bagasse (i.e., "at least a portion of water-insoluble C6-sugar-containing polymers or oligomers, or water-insoluble C5-sugar- containing polymers or oligomers ... are converted to water-soluble C6- sugar monomers, CS-sugar monomers, or any combination thereof'). (FF3.) Pye teaches recovering, via distillation, 5 the spent solvents from black liquor, a product mixture resulting from the organosolv pulping of the sugar cane bagasse comprising "organic solvents containing lignins, lignin- containing compounds, monosaccharides, oligosaccharides, polysaccharides, hemicelluloses and other organic compounds extracted from ... bagasse." (FF3, FF6.) Pye teaches that the stillages separated from the spent solvent comprises, among other things, sugar syrups comprising, e.g., hexoses and pentoses (i.e., "an aqueous solution of carbohydrates comprising C6-sugar 5 Neither Appellants nor the Examiner provided a definition for the claim terms "partitioning" and "extracting." These terms are also not defined in the Specification. We interpret "partitioning" according to its ordinary and customary meaning, which is distributing solutes between two phases in a separation process. See, e.g., "partitioning." COLLINS DICTIONARY, https ://www .co llinsdictionary. com/us/ dictionary I english/partitioning (last visited March 26, 2018) (defining "partitioning" as "when a solute is distributed between two phases in a separation process). We interpret "extracting" according to its ordinary and customary meaning, which is "to withdraw (something, such as ... a constituent element) by physical or chemical process" or "to treat with a solvent so as to remove a soluble substance." See, e.g., "extract." MERRIAM-WEBSTER, www.merriam- webster.com/dictionary/extract (last visited March 26, 2018). Appellants have not disputed that partitioning or extraction may occur by distillation. 11 Appeal2017-006376 Application 13/918,097 monomers, CS-sugar monomers, or a combination thereof'). 6 (FF6.) Finally, Pye teaches using the sugar syrup recovered from the black liquor in the fermentation process. (Id.) Pye does not teach the specific claimed solvent system, i.e., "a solvent system comprising (i) an organic solvent selected from the group consisting of beta-lactones, gamma-lactones, delta-lactones, and combination thereof, and (ii) at least about 1 wt% water." However, Petrus teaches the claimed solvent system for organosolv pulping. In particular, Petrus teaches a solvent for an organosolv pulping process comprising gamma lactone compounds and further teaches that such solvent may also comprise other organic compounds that are known solvents for organosolv pulping, water preferably in an amount up to 20-50%, as well as an acid catalyst. (FF9, FFl 1.) Petrus teaches that using its gamma lactones as a solvent in organosolv pulping is advantageous because the organosolv pulping can be carried out at a relatively low pressure, the solvent is less likely to form reaction products with the lignocellulosic feed material or other components formed in the organosolv process, and a smaller distillation capacity is required. (FF14.) We conclude that a skilled artisan would have reason to use Petrus' solvent system in Pye's process to arrive at the claimed invention, with a reasonable expectation of success, because both Pye and Petrus are directed 6 Pye does not explicitly teach sugar syrup as an aqueous solution. However, Pye suggests that black liquor contains water, because water is recovered when processing the waste materials produced during recovery of organic acids and sugar syrups from the stillage. (FF6; see also Pye Figure 4 and related disclosure.) Thus, we find that Pye suggests sugar syrup as an aqueous solution, at least because sugar is soluble in water. 12 Appeal2017-006376 Application 13/918,097 towards organosolv pulping, Petrus teaches that its solvent system provides certain advantages, and Petrus further teaches that its solvent system may be used with other organic compounds known to be useful as solvents in organosolv pulping. We have considered Appellants' arguments, but do not find them persuasive. Appellants contend that combining Pye and Petrus would not result in the claimed invention because "sugar monomers cannot be partitioned with water from a gamma-lactone solvent using the distillation methods of the cited prior art." (Appeal Br. 5.) In particular, Appellants cite to the boiling point of glucose, gamma-valerolactone, and water and argue that the fact that "gamma-lactone solvent has a boiling point between the alleged sugar monomers and water ... would prevent separating water and the sugar monomers from the gamma-lactone solvent through distillation." (Id.) In other words, Appellants argue that using gamma-valerolactone as a solvent in Pye's process would prevent partitioning or extracting Pye's black liquor into an organic layer (gamma-lactone) and an aqueous layer comprising an aqueous solution of C5- and/or C6-sugar monomers. We are not persuaded. As the Examiner points out, Appellants cite the boiling point of glucose, gamma-valerolactone, and water standing alone. However, the carbohydrates and solvents in the processes taught by Pye and Petrus do not exist as individual components, but as mixtures and/or solutions. (Ans. 4.) Thus, Appellants' evidence and argument that the gamma-lactone solvent cannot be distilled from an aqueous solution of sugars is not persuasive. Appellants contend that the Examiner has failed to provide evidence to "support the general conclusion that the boiling points of the compounds 13 Appeal2017-006376 Application 13/918,097 in pure form are different from their boiling points in a product mixture" or that such a difference would be sufficient "to invert the relative boiling points of the compounds in pure form from their points in a product mixture." (Reply Br. 2, 6-7.) Accordingly, Appellants contend that the Examiner has not shown a reasonable likelihood of success in combining Pye and Petrus to arrive at the claimed invention. (Id.) Appellants also contend that "[i]f the alleged organic layer is intended to be understood as being constituted by an organic component other than the gamma-lactone organic solvent, the present rejection is improper because the [Examiner] has failed to articulate such an organic component, and, accordingly, has also failed to define any 'organic layer' substantially immiscible with respect to the alleged 'aqueous layer' and 'aqueous solution of carbohydrates." (Appeal Br. 5, n. 1; see also id. at 6, 8; Reply Br. 7 (arguing that Examiner has failed to articulate what would constitute the alleged 'organic layer,' 'substantially immiscible aqueous layer,' and 'aqueous solution of carbohydrates' in the alleged combined method).) We are not persuaded. "[E]xpectation of success need only be reasonable, not absolute." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). In this case, as the Examiner also noted, the Specification suggests that a skilled artisan would be able to separate gamma- valerolactone from a substantially immiscible aqueous layer comprising carbohydrates, including via distillation. (Ans. 4; Spec. 5:11-15.) Appellants contend that [t]he reference to distillation in the specification pertains to a separate, optional step performed on the substantially immiscible aqueous layer after the immiscible aqueous layer has been partitioned from the organic layer. The reference to distillation 14 Appeal2017-006376 Application 13/918,097 has nothing to do with the disclosed and claimed partitioning step per se. Nowhere does the specification indicate that water and sugar monomers can be partitioned from a gamma-lactone organic solvent through distillation. (Appeal Br. 7.) The cited portion of the Specification states that the aqueous product stream, i.e., the aqueous solution of carbohydrates, "will generally contain a small amount of [gamma-valerolactone (GVL)]" and further states that an optional step is to "reduce the GVL concentration in the substantially immiscible aqueous layer," which "can be done by any separation means now known or developed in the future, such as distillation, extraction, and the like." (Spec. 5:11-15.) Thus, while we agree with Appellants that the distillation referred to occurs after the initial partition of the organic layer and the substantially immiscible aqueous layer comprising an aqueous solution of carbohydrates, the cited portion of the Specification nevertheless shows that, contrary to Appellants' assertion, gamma-valerolactone in fact may be separated from an aqueous solution of sugar via distillation as proposed by the Examiner in the rejection. 7 7 We further note that Pye teaches butanol as a suitable solvent for its organosolv process (FF2), and it is understood that butanol has a boiling point (117.7 QC) that is between water and sugar. See, e.g., Butyl Alcohol, PUBCHEM OPEN CHEMISTRY DATABASE, https://pubchem.ncbi.nlm.nih.gov/compound/1-butanol#section=Top (last visited March 27, 2018). This fact further supports that a skilled artisan would be able to distill the organic solvents in Pye's process from the sugar syrup in the black liquor, even if an individual organic solvent may have a boiling point between water and sugar. 15 Appeal2017-006376 Application 13/918,097 Appellants also contend that the Examiner improperly "relied exclusively on an alleged teaching by Petrus ... of 'partitioning the product mixture to obtain an aqueous solution of carbohydrates' to provide the partitioning as recited in step (b) in the [claimed] method." (Appeal Br. 7.) Appellants contend that, contrary to the Examiner's suggestion, Petrus does not teach this limitation and that, in any event, a teaching of partitioning the product mixture to obtain an aqueous solution of carbohydrates does not meet the claim limitation of "'partitioning or extracting [a] product mixture into an organic layer and a substantially immiscible aqueous layer." (Id.) We are not persuaded. The Examiner did not rely solely on Petrus to meet the partitioning or extracting step of the claims. Rather, the Examiner explained that Pye teaches "partitioning or extracting a product mixture (black liquor) containing organic solvent and monosaccharides in a liquid fraction (aqueous solution of carbohydrates) and separating the organic solvent to obtain an aqueous solution of carbohydrates." (Final Act. 5.) Appellants' attempts to argue over the cited references individually are not persuasive because "[ n ]on-obviousness cannot be established by attacking references individually where[,] [as here,] the rejection is based upon the teachings of a combination of references." In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellants contend that Pye also does not teach or suggest "partitioning or extracting any product mixture into an organic layer and a substantially immiscible aqueous layer comprising an aqueous solution of carbohydrates comprising C6-sugar monomers." (Reply Br. 3.) In particular, Appellants contend that Pye does not suggest that "the stillage 16 Appeal2017-006376 Application 13/918,097 remaining from the distillation process is an aqueous solution" or that "the recovered organic solvent is substantially immiscible with respect to the remaining stillage." (Id. at 4.) Appellants contend that "the distillation of Pye ... does not inherently partition or extract the spent organic solvent as an organic layer that is substantially immiscible with a second layer, as distillation separates components based on boiling point, not miscibility, and does not inherently generate substantially immiscible layers." (Id.) Likewise, Appellants contend that "there is no evidence in the cited prior art to suggest that a mixture containing the solvents of Pye ... and the gamma- lactone of Petrus ... could be partitioned or extracted into immiscible layers using the distillation taught by these references." (Reply Br. 6.) As an initial matter, we note that Appellants have raised this argument for the first time in the Reply Brief, and Appellants have not explained why this argument could not have been raised earlier. As discussed above, in the Final Action the Examiner explicitly found that Pye teaches the partitioning I extracting step. Accordingly, this argument is waived. See Ex parte Nakashima, 93 USPQ2d 1834 (BPAI 2010) (informative) (explaining that arguments and evidence not timely presented in the principal Brief will not be considered when filed in a Reply Brief, absent a showing of good cause explaining why the argument could not have been presented in the Principal Brief); Exparte Borden, 93 USPQ2d 1473, 1477 (BPAI 2010) (informative) ("Properly interpreted, the Rules do not require the Board to take up a belated argument that has not been addressed by the Examiner, absent a showing of good cause.") Furthermore, we are not persuaded by Appellants' arguments. As discussed above, we find that Pye suggests that the stillage remaining after 17 Appeal2017-006376 Application 13/918,097 the distillation of spent solvents comprises an aqueous solution, because processing of waste materials produced during recovery of organic acids and sugar syrup from stillage results in, among other things, water. (FF6.) This is particularly true when Pye' s teaching is combined with the teaching of Petrus, because Petrus teaches that the solvent used in organosolv pulping preferably contains up to 20-50% water. (FF 11.) With respect to Appellants' argument that there is no evidence that the recycled spent solvent would be substantially immiscible with the remaining stillage, we note that the combination of Pye and Petrus suggests the spent solvent recovered from distillation comprising gamma-valerolactone compounds and the stillage comprises aqueous solutions of sugar. Given the substantial similarity of the reaction and solvent systems suggested by prior art and those claimed, we find that the Examiner has established a prima facie case that the recovered solvent in the organosolv process suggested by the combination of Pye and Petrus (i.e., solvents comprising gamma- valerolactone) would be immiscible with the sugar syrup (i.e., the aqueous solution of sugar). Finally, Appellants contend that a skilled artisan would not have a reason to combine Pye and Petrus. (Reply Br. 4--5.) Appellants contend that "'a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the art.'" Id. at 5 (citation omitted).) Appellants further contend that the Examiner mischaracterized the teachings of Pye. (Id. at 5.) We are not persuaded. Once again, these arguments are raised by Appellants for the first time in the Reply Brief and, so, are waived. Ex parte Nakashima, 93 USPQ2d 1834; Ex parte Borden, 93 USPQ2d at 1477. 18 Appeal2017-006376 Application 13/918,097 Nevertheless, we find on this record that a skilled artisan would have had a reason to combine Pye and Petrus: Pye is directed toward organosolv pulping and Petrus explicitly provides a skilled artisan with reasons to use its solvent system comprising gamma-valerolactones in such a process. (FF14.) Furthermore, we disagree with Appellants' contention that Pye does not teach "a conversion ofwater-[in]soluble C6-sugar-containing polymers present in the biomass to water-soluble C6-sugar monomers" merely because Pye teaches that the pulping process will release monosaccharides from the bagasse into organic solvents rather than water. Whether the monosaccharides are actually released into the organic solvents or water, they remain water soluble. Finally, as already discussed above, we disagree with Appellants' contention that Pye "fails to teach or suggest generating any aqueous solution of carbohyrates comprising C6-sugar monomers that is substantially immiscible with an organic layer." Accordingly, we affirm the Examiner's rejection of claim 1. Claims 2--4, 8-12, 16, and 20-25, which were not argued separately, fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY For the reasons above, we affirm the Examiner's rejection of claims 1--4, 8-12, 16, and 20-25 as obvious. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 19 Copy with citationCopy as parenthetical citation