Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Claims 1, 3, 5, 11-14, 17-20, 26, 27, 30, 37, 42, 47, and 52-54 of I. Klein et al., US 17/627,468 (Apr. 20, 2018) are pending. Claims 37, 42 and 47 to the non-elected inventions of Groups (II) and (III)stand withdrawn from consideration. Elected claims 1, 3, 5, 11-14, 17-20, 26-27, 30 and 52-54 are under examination on the merits and are rejected.
Election/Restrictions
Applicant previously elected of Group I, claims 1, 3, 5, 11-14, 17-20, 26-27, 30 and 52 without traverse in the Reply to Restriction Requirement filed on April 14, 2025. New claims 53 and 54 are added to the invention of Group (I). Claims 37, 42 and 47 to the non-elected invention of Groups (III) stand withdrawn from consideration pursuant to 37 CFR 1.142(b). Applicant has cancelled the invention of Group (II) (i.e., claims 31-32). The Examiner’s restriction/election requirement is maintained as FINAL.
Claim Interpretation
The first step to examining a claim to determine if the language is definite is to fully understand the subject matter of the invention disclosed in the application and to ascertain the boundaries of that subject matter encompassed by the claim. During examination, a claim must be given its broadest reasonable interpretation consistent with the specification as it would be interpreted by one of ordinary skill in the art. MPEP § 2173.01(I); § 2111.01. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. MPEP § 2173.01(I).
Independent Claim 1
Independent claim 1 recites the following extractive process, where the bolded terms are discussed in more detail below:
1. A process for a reactive extraction and subsequent purification of organic molecules from biomass comprising:
extracting one or more products from the biomass using an extraction solvent to solvate the products;
contacting the biomass with a reactant during the extracting;
recovering the one or more products, wherein the one or more products comprise extracted organic molecules comprising a ferulate or a coumarate, wherein the one or more products are separated from the biomass as a liquid extract,
performing ultrafiltration or nanofiltration to remove impurities from the one or more products to produce a filtered extract as the permeate from the ultrafiltration or the nanofiltration,
extracting oils in the filtered extract to produce a de-oiled extract,
performing transesterification or hydrolysis on the de-oiled extract, wherein the ferulate or the coumarate are reacted in the transesterification or hydrolysis to produce ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof;
performing adsorptive purification on the ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof,
wherein ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof are purified to produce one or more purified products
Interpretation of the Claim Term “Biomass”
The instant specification does not provide a closed-ended definition of the term “biomass”. Specification at page 6, [0037]. With respect to “biomass”, the instant specification recites:
[0037] Any suitable biomass can be used as a starting feedstock. Various exemplary biomass feedstocks include, but are not limited to, miscanthus, com bran, com fiber, com gluten feed, distillers' grain, com stover, com gluten meal, beet fiber, rice hulls, and/or other agricultural residues containing ferulate linkages. Wheat bran or other wheat derived materials can also be used as a feedstock for the process described herein.
Specification at page 6, [0037] (emphasis added). The art has recognized “biomass” as living or non-living plants and animals and their waste products. See e.g., K. Tekin et al., 40 Renewable and Sustainable Energy Reviews, 673-687 (2014) (at page 674, col 1: “[b]iomass is a term that encompasses all living or recently passed creatures and their wastes”); The NEED Project Intermediate Energy Infobook (2016). Accordingly, consistent with the specification, the term “biomass” is broadly and reasonably interpreted consistent with the specification as raw or refined plant material.
Interpretation of the Claim Terms “ferulate” and “coumarate”
The instant specification does not specifically define the term “ferulate” or “coumarate”. Ferulic and coumaric acids have the following chemical structures. See e.g., J. Kanski et al., 13 Journal of Nutritional Biochemistry, 273-281 (2002); see also specification at page 1, [0004]; specification at Fig. 4.
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The terms “ferulate” and “coumarate” are broadly and reasonably interpreted, based on the plain meaning of the suffix “ate” in chemistry, and consistently with the specification (see specification at Fig. 4), as limited to the following structural formulae below.
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Interpretation of the Claim Terms “extracting oils in the filtered extract to produce a de-oiled extract”
Claim 1 recites the step of “extracting oils in the filtered extract to produce a de-oiled extract”.
The specification does not provide a closed definition for “oils”. The plain meaning of oil is vague in terms of what structures are encompassed; that is, the plain meaning of “oil” (in the context of claim 1) essentially encompasses any lipid containing component present in the extracted biomass after performing the claim 1 step of “ultrafiltration or nanofiltration”.1 See e.g., Hawley's Condensed Chemical Dictionary, pages 1006-1007 (16th ed., 2016, R.J. Larrañaga ed.); O’Reilly, Talbot & Okun Engineering Blog, Oil – what’s in a name (or definition)? (2008).
With respect to the meaning of the term “oils”, the specification teaches that:
[0008] In some aspects, a process to selectively remove oil from biomass extracts comprises obtaining a biomass extract, and performing liquid-solid adsorption to remove at least a portion of the one or more oils onto a solid phase adsorbent to produce a purified product. The biomass extract is obtained from biomass, and wherein the biomass extract contains a ferulate or a coumarate and one or more oils.
Specification at page 2, [0008] (emphasis added). The specification further teaches that:
In some embodiments, oils including but not limited to esters of oleic acid, oleic acid, esters of linoleic acid, and oleic acid can optionally be removed from the extraction product containing ferulic acid and ethyl ferulate prior to hydrolysis of ethyl ferulate to ferulic acid.
Specification at page 19, [0068]. The specification indicates that Applicant’s intends to encompass at least oleic acid and linoleic acid as well as their esters as the claimed “oils”.
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But note that ferulic and coumaric acids/esters (the claim 1 end products), having a carbon rich component cannot be excluded from the meaning of “oils” under the above interpretation of “oils”.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claims 1, 3, 5, 11-14, 17-19, 26-27, 30 and 52-54 are rejected under AIA 35 U.S.C. 103 as being unpatentable over primary references R. Antrim et al., US 4,038,481 (1977) (“Antrim”) and S. Zhao et al., 92 Food Products Bioprocessing, 309-313 (2014) (“Zhao”) in view of secondary references R. Moreau et al., Biochemical Society Transactions, Phytosterols in the aleurone layer of corn kernels, 803-806 (2000); A. Tilay et al., 56 Journal of Agricultural and Food Chemistry, 7644-7648 (2008) and S. Ou et al., 78 Journal of Food Engineering, 1298-1304 (2007) (“Ou”).
Claim 20 is obvious as above, in further view of D. Revelant et al., US 2016/0145183 (2016) (“Revelant”).
R. Antrim et al., US 4,038,481 (1977) (“Antrim”)
Antrim teaches a process for treating corn hulls to obtain three fractions therefrom comprising a cellulosic fraction, a hemicellulose fraction and a noncarbohydrate fraction. Antrim at col. 1, lines 61-66. In Example 1, Antrim teaches slurrying treated corn hulls in 1000 ml of 69% aqueous ethanol containing 5g of sodium hydroxide (NaOH) and heating in at Parr reactor at 100 ˚C for three hours, then filtering through a Buchner funnel. Antrim at col. 4, line 56 - col. 5, line 21. Antrim thereby obtains the three fractions as summarized schematically below.
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With respect to the above “non-carbohydrate fraction”, Antrim teaches
In the noncarbohydrate fraction, relatively large quantities of ferulic acid and possibly ferulic acid precursors are present. Ferulic acid may be used as an intermediate in the production of vanillin and as a means of controlling discoloration during processing of fruits and vegetables.
Antrim at col. 4, lines 22-28 (emphasis added).
Differences between Antrim and Claim 1
Antrim Example 1 meets each and every limitation of claim 1, except the following claim 1 limitations in strike-out text:
1. A process for a reactive extraction and subsequent purification of organic molecules from biomass comprising:
extracting one or more products from the biomass using an extraction solvent to solvate the products;
contacting the biomass with a reactant during the extracting;
recovering the one or more products, wherein the one or more products comprise extracted organic molecules comprising a ferulate or a coumarate, wherein the one or more products are separated from the biomass as a liquid extract,
performing transesterification or hydrolysis on the de-oiled extract, wherein the ferulate or the coumarate are reacted in the transesterification or hydrolysis to produce ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof;
With respect to the claim 1 limitation of:
Claim 1 . . . performing transesterification or hydrolysis on the de-oiled extract, wherein the ferulate or the coumarate are reacted in the transesterification or hydrolysis to produce ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof;
Antrim teaches the following step in Example 1:
The filtrate was combined with the filtrates from the two previous filtrations, the combined filtrates adjusted to pH2 with HCl, evaporated to dryness and the residue dried in a vacuum oven at 70° C. This product was the noncarbohydrate fraction.
Antrim a col. 5, lines 3-7. This teaching of Antrim meets the above claim 1 “hydrolysis” limitation. Note that one of ordinary skill would be apprised that Antrim’s HCl treatment hydrolysis step was employed to neutralize sodium ferulate salts to the free ferulic acid and/or to hydrolyze extracted ferulic acid esters (as stated by Antium: “possibly ferulic acid precursors are present”, Antrim at col. 4, lines 22-28) to free ferulic acid. See discussion of reference Tilay below; see also footnote 2 below.
With respect to the claim 1 limitation of:
Claim 1 . . . extracting oils in the filtered extract to produce a de-oiled extract . . .
Antrim does specifically address the existence or removal of “oils”. However, as discussed in more detail below regarding reference Moreau, fatty acids (such as oleic acid and linoleic acid, which are “oils” per Claim Interpretation above) are present in the corn hulls extracted by Antrim. See, R. Moreau et al. "Phytosterols in the aleurone layer of corn kernels”, 803-806 (2000), as discussed below. And the oleic acid and linoleic acid that are necessarily present in Antrim’s corn hulls would be extracted into Antrim’s “non-carbohydrate fraction” during the process along with the ferulate acids/esters.
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MPEP § 2112 (V). Prior to Antrim’s acidification/hydrolysis step, each of ferulic, oleic and linoleic acid (which contain ionizable carboxylic acid functional groups) would present as the liquid aqueous/ethanol solution as mixtures of the soluble sodium salts and esters, which all would be converted to free acids in Antrim’s HCl hydrolysis step.2
S. Zhao et al., 92 Food Products Bioprocessing, 309-313 (2014) (“Zhao”)
Zhao teaches that the extraction of corn bran using 0.25 mol/L NaOH aqueous solution containing 50% ethanol (v/v) at 75 °C for 2 h released 81% of the bound ferulic acid. Zhao at page 313 (see “conclusion”). Zhao teaches that ferulic acid can be easily separated by ultrafiltration followed by nanofiltration; it can then be directly crystallized in the retentate after nanofiltration. Zhao at page 313 (“conclusion”).
Zhao teaches that ferulic acid in brans is usually linked to cell wall polymers by ester bond through their carboxylic acid group with the hydroxyl of the α-L-arabinosyl side chains of xylans and the highest content of ferulic acid can be found in corn bran. Zhao at page 309, col. 1. Zhao teaches that ester-bound ferulic acid can be easily released by alkaline treatment. Zhao at page 309, col. 2. Such alkaline treatment would thus produce a mixture of polysaccharides and the released ferulic acid.
Zhao teaches that purification of ferulic acid from corn bran using macroporous resin exchange chromatography requires removal of viscous polysaccharides because they adhere to the resin and greatly influence separation. Zhao at page 309, col. 2.
Zhao teaches that ferulic acid (4-hydroxy-3-methoxycinnamic acid) is widely used in the food, medical and cosmetic industries and has several physiological functions, including antioxidant, antimicrobial, anti-inflammatory, anticancer and free radical scavenging activities, and also prevents coronary disease, lowers serum and liver cholesterol and increases sperm viability. Zhao at page 309, col. 1.
Zhao teaches that ferulic acid in brans is usually linked to cell wall polymers by ester bond through their carboxylic acid group with the hydroxyl of the α-L-arabinosyl side chains of xylans and the highest content of ferulic acid can be found in corn bran. Zhao at page 309, col. 1. Zhao teaches an alkaline-ethanol aqueous solution was used to release the bound ferulic acid, resulting in a less viscous hydrolysate with low hemicellulose content and ferulic acid was separated sequentially by ultrafiltration, nanofiltration and crystallization. Zhao at page 310, col. 1.
Zhao provides a flow chart of this process in Fig. 1.
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Zhao at page 311, col. 1 (Fig. 1).
Zhao teaches that the corn bran used in the extraction experiments was oven dried at 105 °C for 6 h and then ground to pass a 45-mesh sieve. Zhao at page 310, col. 1.
Zhao first teaches optimization of the reactive extraction of the corn bran using a sodium hydroxide (NaOH), water, and ethanol system. Zhao at page 310, col. 1 (under “2.2. Extraction of ferulic acid by alkaline hydrolysis”, see date at page 312, Table 1). Zhao teaches that as a result of this optimization, when one weight of corn bran was extracted in 10 volumes of NaOH/ethanol/water (0.25 M:1:10) at 75 °C for 2 h (Test NO. 2 in Table 1), 83% of the bound ferulic acid was released, and the viscosity of the extracts was relatively low. Zhao at page 311, col. 1. Zhao concludes that the Test NO. 2 extraction conditions of Table 1 are the optimal balance of extracted ferulate amount versus extraction solution viscosity for subsequent filtration tests. Zhao at page 311, col. 1.
Zhao teaches the following ultrafiltration process:
In this research, when ethanol was added into aqueous NaOH solution at 50%, the hydrolysates were concentrated easily by ultrafiltration. Increasing the pressure increased the permeate flux, ferulic acid permeability, and concentration factor; however, the values of the three parameters reached a plateau after 1.0 bar (Fig. 2). After ultrafiltrating 10 L of the extracts, the concentration factor reached 4.3 in 30 min at 1.0 bar, and 75.6% of the released ferulic acid was retained in the permeates (Fig. 2). Approximately 2.0 L ferulic acid was retained in the ultrafiltration equipment. When the concentration reached 4.3, the retenate was diluted using 2.0 L water and further ultrafiltrated twice. As a result, the transmissivity of ferulic acid reached 86.4% and 91.8%.
Zhao at page 311, col. 2. Zhao also teaches the following nanofiltration process:
Nanofiltration can effectively separate phenolic compounds. Given that corn bran contains a small amount of lignin, we employed nanofiltration to concentrate the permeates from ultrafiltration and purify ferulic acid through direct crystallisation of ferulic acid by acidifying the rententate. As shown in Table 2, both pressure and solution temperature influenced the permeate flux of nanofiltration. When the pressure and temperature were kept at 4.5 bar and 45 °C, respectively, the permeate flux reached 29.3 L/m2h. After nanofiltrating 10.0 L of the ultrafiltration permeates, the concentration factor reached 5.3 in 80 min at 4.5 bar, and 94.6%of the released ferulic acid from corn bran was recovered in the retentates (Fig. 3).
Zhao at paragraph bridging pages 311-312 (emphasis added).
With respect to isolation of the ferulic acid by crystallization after the above corn bran extraction, ultrafiltration, and nanofiltration Zhao teaches that:
After the concentration factor reached 5.0, the concentrates were acidified to pH 2.0. Crystal was collected by filtration followed by lyophilisation. The powdered products contained 84.4% of ferulic acid, as determined by HPLC. It yielded 8.47 g/kg of ferulic acid after extraction, ultrafiltration, nanofiltration, and crystallisation, amounting to 50.1% of the original ferulic acid in corn bran. This research revealed that ferulic acid was lost mainly in the processes after extraction, indicating that the output can be further increased by raising the concentration factor of ultrafiltration and nanofiltration.
Zhao at paragraph bridging pages 312-313.
R. Moreau et al. "Phytosterols in the aleurone layer of corn kernels”, 803-806 (2000)
Moreau is cited here as evidence that one of ordinary skill would be apprised that oleic acid and linoleic acids/esters (claim 1 “oils” per Claim Interpretation) are necessarily present in Antrim’s corn hulls and would be extracted (along with the desired ferulate acids/esters) into Antrim’s “non-carbohydrate fraction” (the ferulate fraction) during Antrim’s process.
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MPEP § 2112 (V).3 One of ordinary skill is motivated to obtain pure ferulic acid and is therefore form motivated to remove such oleic acid and linoleic acids/esters.
In this regard, Moreau teaches that corn hulls are composed of an outer layer (pericarp) and an inner layer (aleurone). Moreau teaches high levels of ferulate esters in corn hulls (particularly in the aleurone layer):
This study revealed that the high levels of ferulate-phytosterol esters and the high concentration of sitostanol previously reported in corn-fibre oil actually originate in the aleurone cells.
Moreau at page 803, col. 1. Moreau teaches that wet milled corn hulls are composed of a fine fiber and a coarse fiber as follows:
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Moreau at paragraph bridging pages 803-804.
Moreau teaches that corn hulls were wet milled and the fiber, germ, aleurone and pericarp layers were separated and dried
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Moreau at page 804, col. 1. Moreau that each of the four separated portions were extracted with hexane and the hexane removed to give an oil extract.
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Per Table 2 summary of the GC analysis, Moreau teaches that the aleurone extract (inner layer of the corn hull) as well as the germ and fiber extract all contained roughly equal amounts of linoleic and oleic acids.
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Moreau at page 805, Table 2. This provides sufficient evidence that the aleurone layer of corn hulls (for example those of reference Antrim) comprise linoleic and oleic acids (as well as the desired ferulic esters).
A. Tilay et al., 56 Journal of Agricultural and Food Chemistry, 7644-7648 (2008)
Tilay teaches that alkaline extraction is useful to extract ferulic acid from plants. Tilay at page 7644, col. 1. Tilay teaches the following with respect to alkaline extraction.
The extraction method may affect the yield and profile of phenolic acids released because these exist in esterified forms in plant cell walls. Alkaline treatment essentially involves hydrolytic cleavage of ester linkages between lignin and plant polysaccharides thereby releasing phenolic acids. In this study, only esterified FA (EFA) was released by alkaline treatment and the etherified FA leftovers as it is in residue.
Tilay at page 7644, col. 1 (emphasis added). Tilay teaches alkaline extraction of ferulic acid from various plant sources (maize bran, sugar cane baggasse (SCB), rice bran, wheat bran, wheat straw, pineapple peels, orange peels, and pomegranate peels) with NaOH (2 M, 60 mL) for 24 h at room temperature on a rotary shaker at 180 rpm. To prevent degradation and/or oxidation of FA, 0.001 g of sodium hydrogen sulfite was added to the solution. The alkaline hydrolysate was centrifuged, the supernatant was acidified (pH < 2) with dilute hydrochloric acid (2 M), and the released phenolic acids were extracted using ethyl acetate (60 mL, thrice). Tilay at page 7645, col. 1. One of ordinary skill would be apprised that Tilay’s step of “the supernatant was acidified (pH < 2) with dilute hydrochloric acid (2 M), and the released phenolic acids” was required to hydrolyze the extracted ferulic acid esters to free ferulic acid.
In the experimental section, Tilay teaches that accurately weighed 2 g of sample (of Maize bran, sugar cane baggasse (SCB), rice bran, wheat bran, wheat straw, pineapple peels, orange peels, and pomegranate peels) was taken into an Erlenmeyer flask (250 mL) and saponified with NaOH (2 M, 60 mL) for 24 h at room temperature on a rotary shaker at 180 rpm then the mixture was centrifuged, the supernatant acidified, extracted with ethyl acetate, concentrated and the concentrate extract dissolved in 2 ml acetonitrile /water for quantitative analysis . Tilay at page 7645, col. 1 under “Materials and Methods”.
Tilay teaches that that quantitative analysis is preformed Jasko high-performance liquid chromatography (HLC) system. Tilay at page 7645, col. 1-2. Tilay teaches that purification of ferulic acid was studied by using three matrices viz. polyvinyl polypyrrolidone (PVPP), Amberlite XAD-4, and Amberlite XAD-16. Id. at col. 2. Tilay teaches that the elution profile of ferulic acid from Amberlite XAD-16 is shown in Figure 3 giving a 50.89% HPLC purity along with 57.97% recovery, and the fold purity was increased to 1.35. Tilay at page 7647, col. 1. Tilay teaches that with ferulic acid, there are other phenolic acids present and to further purify ferulic acid, preparative HPTLC was carried out to give HPLC purity of the ferulic acid up to 95.35%. Tilay at page 7647, col. 2.
Tilay thus teaches extraction, analysis and purification of natural product extracts of ferulic acid by way of HPLC.
S. Ou et al., 78 Journal of Food Engineering, 1298-1304 (2007) (“Ou”)
Ou teaches that sugarcane bagasse was used to prepare highly valued trans-ferulic acid by alkaline-hydrolysis and purification through combination of activated charcoal adsorption and anion macroporous resin exchange chromatography. Ou at Abstract.
Ou teaches the following experimental procedure to extract a ferulate containing extract from sugarcane followed by ultrafiltration:
Triplicates of 2000 g of sugarcane bagasse was mixed with 20 l of solution which contained 0.5 mol/l NaOH and 100 mg/l NaHSO3 (to prevent ferulic acid oxidation according to Ou et al., 2002) in a 30-l reactor and reacted at 50 °C, 160 r/min for 4 h. The mixture was centrifuged in a basket centrifuge and the residue was washed by 2000 ml water for twice. Mixing the filtrate and kept at 4 °C for 12 h, the decant supernatants were adjusted to pH 7.0 using HCl and filtrated using a ultrafiltration equipment with 20000 molecular cutoff, the filtrate was collected for purification of ferulic acid, and the concentration of ferulic acid in the filtrate was determined spectrophotometricately at 320 nm using a UV-2101 PC UV–VIS Scanning Spectrophotometer (Shimadzu) according to Ou, Li, and Yang (2001).
Ou at page 1299, col. 2.
Ou teaches that the above obtained hydrolysate was further purified by activated charcoal. Ou at page 1300, cols. 1-2 (“2.3. Batch tests”). Ou teaches that high purity of ferulic acid could be obtained by anion macroporous resin exchange chromatography after its washout from the activated charcoal. Ou at page 1303, col. 1 (“Conclusion”).
Obviousness Rational
Claim 1 is obvious for the following reasons. One of ordinary skill is motivated to treat the Antrim filtrate (from extraction of corn hulls), obtained in Antrim Example 1 as follows:
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by ultrafiltration as taught by Zhou or Ou. Zhao at page 311, col. 1 (Fig. 1); Ou at page 1299, col. 2.
One of ordinary skill is so motivated because Antrim teaches that “[i]n the noncarbohydrate fraction, relatively large quantities of ferulic acid and possibly ferulic acid precursors are present”. Antrim at col. 4, lines 23-25. One of ordinary skill is informed by Tilay that such “precursors” are esters of ferulic acid. Tilay at page 7644, col. 1. One of ordinary skill is also apprised by Zhao that Antrim’s filtrate also comprises amounts of higher molecular weight polysaccharides. Zhao at page 309, col. 2.4 One of ordinary skill seeking pure ferulic acid is motivated to remove such higher molecular weight polysaccharides by ultrafiltration as taught by Zhao for corn bran because Zhao specifically teaches the effectiveness of this process for corn bran. One of ordinary skill has a reasonable expectation that the Zhou ultrafiltration process would also be an effective purification technique for the Antrim corn-hull extract. Zhao at page 311, col. 1 (Fig. 1). Thus, so far, one of ordinary skill thereby meets each and every limitation of claim 1, except the following claim 1 limitations in strike-out text:
1. A process for a reactive extraction and subsequent purification of organic molecules from biomass comprising:
extracting one or more products from the biomass using an extraction solvent to solvate the products;
contacting the biomass with a reactant during the extracting;
recovering the one or more products, wherein the one or more products comprise extracted organic molecules comprising a ferulate or a coumarate, wherein the one or more products are separated from the biomass as a liquid extract,
performing ultrafiltration or nanofiltration to remove impurities from the one or more products to produce a filtered extract as the permeate from the ultrafiltration or the nanofiltration,
One of ordinary skill is further motived to practice the claim 1 step of:
Claim 1 . . . extracting oils in the filtered extract to produce a de-oiled extract . . .
to enhance the purity level, where “oil” is broadly and reasonably interpreted essentially as any lipid containing compound. For example, one of ordinary skill is informed by Moreau that oleic acid and linoleic acids/esters (claim 1 “oils” per Claim Interpretation) are necessarily present in Antrim’s corn hulls and would be extracted (along with the desired ferulate acids/esters) into Antrim’s “non-carbohydrate fraction” (the ferulate fraction) during Antrim’s process.
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MPEP § 2112 (V). One of ordinary skill is motivated to obtain pure ferulic acid and is therefore form motivated to remove such oleic acid and linoleic acids/esters (claim 1 “oils” per Claim Interpretation). One of ordinary skill would understand that the relatively lower molecular weight oleic acid and linoleic acids/esters would not be removed during the ultrafiltration. One of ordinary skill is motivated to remove oleic acid and linoleic acids/esters using standard organic chemistry purification techniques, such as chromatography, for example, preparative HPLC as taught by Tilay, where Tilay teaches that with ferulic acid, there are other phenolic acids present and to further purify ferulic acid, preparative HPTLC was carried out to give HPLC purity of the ferulic acid up to 95.35%. Tilay at page 7647, col. 2. Alternatively, one of ordinary skill could employ anion macroporous resin exchange chromatography and/or activated charcoal as taught by Ou. Ou at page 1303, col. 1 (“Conclusion”).
One of ordinary skill is further motivated to perform the claim 1 step of:
Claim 1 . . . performing transesterification or hydrolysis on the de-oiled extract, wherein the ferulate or the coumarate are reacted in the transesterification or hydrolysis to produce ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof;
for example, by treatment of the above-obtained de-oiled hydrolysate with HCl as taught by Tilay to release the phenolic acids from ferulic esters and/or convert ferulate salts to free acids. Tilay at page 7645, col. 1.
One of ordinary skill is further motivated to perform the claim 1 step of:
Claim 1 . . . performing adsorptive purification on the ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof,
wherein ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof are purified to produce one or more purified products.
to further increase the purity of the ferulic acid. For example, using standard organic chemistry adsorptive purification techniques, such as chromatography, for example, preparative HPLC as taught by Tilay, where Tilay teaches that with ferulic acid, there are other phenolic acids present and to further purify ferulic acid, preparative HPTLC was carried out to give HPLC purity of the ferulic acid up to 95.35%. Tilay at page 7647, col. 2. Alternatively, one of ordinary skill could employ anion macroporous resin exchange chromatography and/or activated charcoal as taught by Ou. Ou at page 1303, col. 1 (“Conclusion”). Each and every claim 1 limitation being met by the cited art, claim 1 is obvious.
The limitations of claim 3 are clearly met because Antim employs filtration and solid-liquid separation.
Claim 5 is obvious for the following reason. One of ordinary skill is motivated to treat the obtained de-oiled hydrolysate (as proposed above) with HCl as taught by Tilay to release the phenolic acids from ferulic esters and/or convert ferulate salts to free acids. Tilay at page 7645, col. 1. One of ordinary skill is informed by Zhou that ferulic acid precipitates from the HCl treated solution. Zhao at page 310, col. 2 (teaching that “[a]fter nanofiltration, the retentate was adjusted to pH 2.0 with 6.0 mol/L HCl and then kept at room temperature for 24 h for crystallization”). One of ordinary skill is motived to perform a subsequent recrystallization to further improve the purity. For example, Taniguchi et al., US 5,288,902 (1994) (“Taniguchi”) teaches that the purity of ferulic acid can be improved by recrystallization. Taniguchi at col. 3, lines 50-55.
Claim 11 is obvious because Antim employs 1000 ml 69% aqueous ethanol (v/v) and 5g NaOH, which is a 0.125 N in NaOH, which falls within the claim 11 range.
The limitations of claim 12 are clearly met by Antim’s use of corn hulls, which (per Moreau) comprise both corn bran and corn fiber.
Claim 13 is an obvious variation of the proposed cited art combination for the following reasons. In Example III, Antrim teaches that 100% water can be used as the extraction solvent. In Example III, Antrim teaches the following procedure:
A mixture of 22.8 ml water and 5 g NaOH was added to 50 g of the dried hulls and the slurry stirred, placed in a container which was sealed and heated at about 90 C for six hours in a hot water bath.
Antrim at col. 6, lines 50-54.
The limitations of claim 14 are met because Antrim teaches that the solvent comprise 690 g water 410 g of ethanol. Thus, Antrim’s amounts fall within the claim 20 range. MPEP § 2144.05(I) (in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (citing In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)). The corn hulls employed by Antrim meet the claim 14 limitation of “wherein at least a portion of the water is supplied by the biomass” because the cited Antrim Example 1 teaches that “[the corn hulls] were dried to a moisture range of 5 to 10 percent in a forced air oven at 70°C”. Antrim at col. 4, lines 55-56. Thus, the Antrim corn hulls comprise moisture/water will meet the claim 14 limitation of “wherein at least a portion of the water is supplied by the biomass”.
The limitations of claim 17 are met because Antrim teaches that the solvent comprise 690 g water 410 g of ethanol and 52 g of biomass which amounts to solvent to biomass ratio of 19:1. Thus, Antrim’s amounts fall within the claim 17 range. MPEP § 2144.05(I) (in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (citing In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)).
The limitations of claim 18 are met by practice of Antrim Example 1 as proposed above because Antrim employs Parr model 4522 pressure reactor at 100 C for 3 hours. Antrim at col. 6, lines 57-61.
The limitations of claim 19 are met because Antrim employs Parr model 4522 pressure reactor, which is (per claim 19) a pressurized batch reactor.
Claim 20 is obvious as above, in further view of D. Revelant et al., US 2016/0145183 (2016) (“Revelant”). Revelant teaches treatment of said plant material followed by a solid/liquid separation to recover a solid phase and an aqueous liquid phase comprising the ferulic acid and said polysaccharides. Revelant at page 1, [0006]. Revelant teaches that the process of the invention consists in subjecting the plant material to an alkaline decoction and/or to an enzymatic treatment so as to release the chemical species constituting or linked to the cellulose or the hemicellulose of the starting plant; whereby ferulic acid and the polysaccharides are released. Revelant at col. 1, [0013].
Revelant teaches that:
The treatment by alkaline decoction (step 1) consists in macerating and cooking said plant material in an alkaline Solution or an alkaline Suspension. The plant material/alkaline solution weight ratio is between 0.05 and 0.5. The content of base in the alkaline solution is between 1% and 30% by weight. The base used for this treatment is advantageously selected from Sodium hydroxide, potassium hydroxide and sodium carbonate. The temperature at which the alkaline decoction is carried out is preferentially between 60 and 120°C. The operating time of this treatment is preferentially between 2 and 8 hours. The alkaline decoction is advantageously carried out using a stirred tank equipped with a stirring spindle, a heating jacket and counter-paddles making it possible to optimize the material and energy transfer conditions. The raw plant material is introduced into said tank containing a dilute alkaline Solution. At the end of the decoction, the mixture obtained is a two-phase mixture: the solid phase contains constituent cellulose and hemicellulose fibers of the plant cell walls, while the liquid phase contains dis solved polysaccharides, elementary sugars, mineral salts, proteins and salified ferulic acid.
Revelant at pages 1-2, [0014] (emphasis added). Revelant teaches that “[f]or example, in the twin-screw extruder, it is possible to continuously feed the plant material to be treated and the alkaline solution by finely controlling the flow rates, temperature and arrangement of the internal screw threads (conveying, blending and/or counter-screw)”. Revelant at page 2, [0015]. Revelant teaches that “[t]hese grinders can be used while being immersed in the alkaline solution or can be controlled online. An online grinder and a stirred tank can in particular be coupled so as to have a sufficient residence time (for example 2 to 8 hours of alkaline decoction) and an intensification of the contact between plant fibers and alkaline solution.” Revelant at page 2, [0016]. Revelant thus teaches that (per claim 20) a continuously operated stirred tank reactor is suitable equipment to extract ferulic acid from corn products using alkaline sodium hydroxide, as taught by Antrim. Note that Revelant further teaches that preferably, said step of selective separation of the polysaccharides is carried out by ultrafiltration by means of an organic or inorganic membrane, preferentially an inorganic membrane. Revelant at page 2, [0022]. One of ordinary skill is motived to employ the continuous stirred tank/ultrafiltration technique of Revelant to Antrim’s extraction procedure (as proposed in the above § 103 rational) thereby meeting each and every claim 20 limitation.
The limitations of claim 26 are clearly met by the above-proposed § 103 rational in which the ethanol is removed and ferulate ester is converted to ferulic acid using a hydrolysis reaction.
Claim 27 is obvious because Zhou teaches the ethanol-removed extracts were ultrafiltrated using an NUFmodel hollow fiber ultrafiltrator (Wuxi Ultrafiltrating Equip-ment Company, Jiangsu Province, China) with a 5000 Da molecular cut-off membrane. Zhou at page 310, col. 1. The Zhou 5000 Da cutoff range falls within the claim 27 range of 300-10,000 Daltons.
Claim 30 is obvious for the following reasons. With respect to the meaning of the claim 30 recitation of “carried out in multiple stages with one or more diafiltration steps, wherein 0.2 - 2 diafiltration volumes of clean solvent are used in each diafiltration step”, is the working example at page 41. Specification at page 41, [0130]. With respect to a diafiltration step, this working example teaches that:
A first diafiltration was then carried out to recovery more ferulate by re-diluting the retentate with 550 mL of clean anhydrous ethanol and restoring the solution to its original volume of 700 mL. The extract was then continuously circulated over the retentate side of the membranes at 1 L/min using a gear pump while heating the fluid inside the system to 50 °C using a hot plate, then the system was pressurized to 30 barg using nitrogen gas.
. . .
A second diafiltration was then carried out to recovery more ferulate by re-diluting the retentate with 590 mL of clean anhydrous ethanol and restoring the solution to its original volume of 700 mL.
Specification at pages 41-42, [00130] (emphasis added). The concept of claim 30 is akin to washing a filter cake after filtration to increase the efficiency of recovering desired product. In the above specification working example, the retentate is the concentrated larger molecular weight material that remains on the membrane after the smaller molecules (ferulates etc.) have passed through. Per the teachings of Zhou and Revelant, one of ordinary skill would understand that this retentate would consist mainly of polysaccharides meant to be separated in the first place, along with residual ferulic acid. Zho teaches the further limitations of claim 30 because Zhou teaches that “[r]etentate was diluted and re-ultrafiltrated twice by adding 2.0 L water in each”. Zhou at page 310, col. 2. One of ordinary skill is motivated to perform the claim 30 step of “wherein the filtration is carried out in multiple stages with one or more diafiltration steps, wherein 0.2 - 2 diafiltration volumes of clean solvent are used in each diafiltration step”, as directly taught by Zho, in order to improve the efficiency of ferulate recovery.
Claim 52 recites:
52. The process of claim 1, wherein the ferulic acid, coumaric acid, ferulate, coumarate, or a combination thereof comprises ferulic acid, and
wherein the ferulic acid is purified with an ion exchange process comprising: adsorption of the ferulic acid to a strong or weak anion exchange resin by the formation of the ionic bonds between the carboxylic acid molecule and exchange sites on the resin,
washing the resin with a liquid such as water or solvents, including ethanol, to remove unbound contaminants that are trapped in the ion exchange resins
displacement of the ferulic acid from the resin by exchanging the adsorbed carboxylic ion for a stronger, inorganic ion,
thereby causing the release of the ferulic acid,
preparation of the anion exchange resin for further cycles of ferulic acid adsorption by regenerating the anion exchange sites on the resin by treating the resin with a strong base,
which causes the inorganic anion to be exchanged for a hydroxide ion.
As discussed above Ou teaches extracting a ferulate containing extract from sugarcane followed by ultrafiltration. Ou at page 1299, col. 2.
Ou teaches the following purification of ferulic acid using anion macroporous resin exchange chromatography:
2.3.2. Further purification of ferulic acid using anion macroporous resin exchange chromatography D201 was purchased from the Chemical Company of Nankai University, which is a strong-alkali anion macroporous resin. The resin was treated before use according to the following procedure: rinsed in 10 volume of deionized water for 24 h, decanted water, and rinsed in 3 volume of 2.0% HCl for 4 h, washed out with deionized water to neutral pH; and then rinsed in 5 volume of 5% NaOH for 24 h and washed out with deionized water to neutral pH.
Three hundred milliliter of the resin, nearly 4 times of the maximum of ion exchange capacity for ferulic acid (83.66/ml, according to Liu et al., 2004), was loaded upwards in a column (i.d. = 8cm). The precipitates obtained in 2.3.1 were dissolved in 1500 ml of alkali solution (pH = 9.0, NaOH) and loaded upwards in the column, the elution rate was kept at 5 ml/ min by a peristaltic pump,
the resin was washed out by 1000 ml of deionized water and then by 1000 ml of ethanol at 30 ml/min. Ferulic acid was desorbed using 1000 ml HCl/ethanol/H2O (4:60:36) at 5 ml/min, which was the optimal elution condition in our previous research (Liu et al., 2004). The first 200 ml of eluents was discarded and the later 800 ml of eluents was vacuum-evaporated to 200 ml, kept at 4 °C for 12 h, the crystal ferulic acid was obtained and its purity was determined by TLC test.
Ou at page 1300, col. 2. The above procedure of Ou meets each and every limitation of claim 52, except the following:
52. preparation of the anion exchange resin for further cycles of ferulic acid adsorption by regenerating the anion exchange sites on the resin by treating the resin with a strong base,
which causes the inorganic anion to be exchanged for a hydroxide ion.
This is an obvious limitation for the following reasons. One of ordinary skill is motivated to regenerate the anion exchange sites on the resin by treating the resin with a strong base in order to regenerate the resin for a subsequent use.
New claim 53 is the same as previous claim 1. That is claim 53 differs from instant claim 1 only in that it does not recite the most recent amendment of “as the permeate from the ultrafiltration or the nanofiltration”
. . . performing ultrafiltration or nanofiltration to remove impurities from the one or more products to produce a filtered extract as the permeate from the ultrafiltration or the nanofiltration . . .
Claim 53 is therefore obvious for the same reasons as claim 1.
New claim 54 is the same as claim 5 except that it is dependent upon new claim 53. New claim 54 is obvious for the same reasons as claim 5 above.
Applicant’s Argument that the cited art does note teach or suggest performing ultrafiltration or nanofiltration to remove impurities to produce a filtered extract as the permeate
Applicant argues that none of Antrim, Zhao, Moreau, Tilav, or Ou teach or suggest the claim 1 step of:
Claim 1 . . . performing ultrafiltration or nanofiltration to remove impurities from the one or more products to produce a filtered extract as the permeate from the ultrafiltration or the nanofiltration . . .
Applicant states that the amendment to claim 1 (indicated above by underlining) is intended to clarify that the process requires collecting the ferulate-containing extract as what passes through the membrane (the permeate), not as what is retained by the membrane (the retentate).
Examiner Response
This argument is not persuasive because Zhao does teach that the ultrafiltration permeate is the desired fraction that comprises ferulic acid. That is Zhao teaches the following ultrafiltration process:
In this research, when ethanol was added into aqueous NaOH solution at 50%, the hydrolysates were concentrated easily by ultrafiltration. Increasing the pressure increased the permeate flux, ferulic acid permeability, and concentration factor; however, the values of the three parameters reached a plateau after 1.0 bar (Fig. 2). After ultrafiltrating 10 L of the extracts, the concentration factor reached 4.3 in 30 min at 1.0 bar, and 75.6% of the released ferulic acid was retained in the permeates (Fig. 2). Approximately 2.0 L ferulic acid was retained in the ultrafiltration equipment. When the concentration reached 4.3, the retenate was diluted using 2.0 L water and further ultrafiltrated twice. As a result, the transmissivity of ferulic acid reached 86.4% and 91.8%.
Zhao at page 311, col. 2 (emphasis added). Zhao further takes the ultrafiltration permeates, obtained as above to a next step of nanofiltration. As correctly argued by Applicant, Zhao teaches that nanofiltration is used to concentrate ferulic acid by retaining it in the retentate while permeating solvent. But as proposed in the obviousness rationale, one of ordinary skill seeking pure ferulic acid is motivated to remove higher molecular weight polysaccharides from Antrim’s filtrate by ultrafiltration as taught by Zhao for corn bran because Zhao specifically teaches the effectiveness of this process for corn bran. In sum, while as argued by Applicant, Zhao's process employs a nanofiltration (with a 150 Da molecular weight cutoff) to concentrate ferulic acid in the retentate by selectively permeating the solvent while retaining the ferulic acid, it is the Zhao’s ultrafiltration (with a 5000 Da molecular cut-off membrane) that one of ordinary skill is motivated to employ to remove polysaccharides from Antrim’s filtrate.
Applicant’s Argument that the cited art does not teach or suggest extracting oils in the filtered extract to produce a de-oiled extract after an ultrafiltration or nanofiltration step
Applicant further argues that Antrim, Zhao, Moreau, Tilay, or Ou do not teach the claim 1 or 53 limitation of:
Claims 1 and 53 . . . extracting oils in the filtered extract to produce a de-oiled extract . . .
Applicant argues that the previous Office action attempts to bridge this critical gap by relying on Moreau to establish that "oleic acid and linoleic acids/esters (claim 1 'oils' per Claim Interpretation) are necessarily present in Antrim's corn hulls and would be extracted" into the ferulate-containing fraction. Applicant argues that Moreau is limited to compositional analysis of different corn kernel fractions and does not teach or suggest any extraction or purification process, let alone membrane filtration or oil extraction from filtered extracts. Applicant further argues that Moreau does not teach or suggest anything related to ultrafiltration, nanofiltration, or extracting oils from a filtered extract obtained after such membrane filtration processes. Applicant argues that Moreau simply characterizes what lipids are present in raw corn fractions-it provides no teaching about what happens to oils during processing or whether oil extraction would be necessary or desirable after ultrafiltration or nanofiltration of a ferulate extract.
Examiner Response
This argument is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. MPEP § 2145(IV). It is true as Applicant argues above that Moreau does not teach ultrafiltration, nanofiltration, or extracting oils from a filtered extract obtained after such membrane filtration processes. However, the § 103 rationale is based on what a person of ordinary skill in the pertinent art would have known at the relevant time, and on what such a person would have reasonably expected to have been able to do in view of that knowledge; regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. MPEP § 2141(II) (discussing the flexible approach of KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Here, as discussed in detail above, one of ordinary skill is informed by Moreau that oleic acid and linoleic acids/esters (claim 1 “oils” per Claim Interpretation) are necessarily present in Antrim’s corn hulls and would be extracted (along with the desired ferulate acids/esters) into Antrim’s “non-carbohydrate fraction” (the ferulate fraction) during Antrim’s process. One of ordinary skill is motivated to obtain pure ferulic acid and is therefore form motivated to remove such oleic acid and linoleic acids/esters. Further, one of ordinary skill would understand that the relatively lower molecular weight oleic acid and linoleic acids/esters would not be removed during the proposed ultrafiltration. One of ordinary skill is motivated to remove oleic acid and linoleic acids/esters using standard organic chemistry purification techniques.
Applicant further argues that claim 1 and new claim 53 recites an integrated purification process that includes a specific sequence of steps: reactive extraction, ultrafiltration/nanofiltration, oil extraction by adsorption, transesterification/hydrolysis, and adsorptive purification. This integrated approach represents a synergistic combination of purification technologies applied in a specific sequence to achieve high-purity ferulate and coumarate products. Applicant argues that the § 103 rationale has not established that this integrated sequence is taught or suggested by the prior art. Applicant argues that each of the cited references teaches different purification approaches for different purposes, and none suggests the specific integrated sequence claimed.
This argument is not persuasive for the following reasons. An Office action’s § 103 rationale typically cites a combination of references, explains how the combination teaches each and every claim element, and provides motivation to combine the cited references in a manner so to arrive at the claimed invention with a reasonable expectation of success. MPEP § 2144.
Here, Antrim teaches a simple extraction methodology to arrive at an impure “non-carbohydrate fraction”, where Antrim teaches
In the noncarbohydrate fraction, relatively large quantities of ferulic acid and possibly ferulic acid precursors are present. Ferulic acid may be used as an intermediate in the production of vanillin and as a means of controlling discoloration during processing of fruits and vegetables.
Antrim at col. 4, lines 22-28 (emphasis added). One of ordinary skill is motivated to build upon Antrim’s work by further purifying his noncarbohydrate fraction using subsequently published references teaching applicable purification techniques, such as ultrafiltration as taught by Zhou and extracting oils (where Moreau informs one of ordinary skill of their likely presence) in order to arrive at purified ferulic acid.
Applicant’s Argument that Antrim teaches away from having oils present after preprocessing.
Applicant argues that § 103 rationale’s premise that oils would necessarily be present in the extract requiring removal is directly contradicted by Antrim's own disclosure. Applicant argues that Antrim explicitly teaches removing oils and lipids during the preprocessing step, before the reactive extraction process that produces the ferulate-containing non-carbohydrate fraction. Applicant thus argues that one of ordinary skill does not have motivation to perform the claim 1 and 53 step of:
Claims 1 and 53 . . . extracting oils in the filtered extract to produce a de-oiled extract . . .
Applicant argues that Antrim Example 1 teaches that the corn hulls were treated as follows:
Antrim Example 1 . . . Corn hulls from a corn wet milling operation were wet screened through a U.S. No. 6 screen at about 50 ˚C using sufficient water to substantially remove the fine fiber, most of the starch and some of the protein and lipid material present.
Antrim at col. 4, lines 46-50, Example 1 (emphasis added).
Applicant argues that Antrim's process is specifically designed to remove lipid material during the preprocessing stage, before the com hulls undergo the alkaline extraction process that produces the non-carbohydrate fraction containing ferulates. Therefore, Antrim's non-carbohydrate fraction would have reduced or minimal oil content, contradicting the examiner's assertion that oils would "necessarily" be present in quantities requiring subsequent extraction.
Examiner Response
Applicant’s argument is not persuasive because Antrim teaches that only “some of the protein and lipid material present” are removed; thus, conversely some fatty acid esters still remain in the corn hulls themselves and would thus necessarily still be present in Antrim’s Example 1 slurry during the extraction with sodium hydroxide. This is evidence as follows. Antrim Example 1 teaches that the corn hulls were treated as follows:
Antrim Example 1 . . . Corn hulls from a corn wet milling operation were wet screened through a U.S. No. 6 screen at about 50 ˚C using sufficient water to substantially remove the fine fiber, most of the starch and some of the protein and lipid material present.
Antrim at col. 4, lines 46-50, Example 1 (emphasis added). Antrim teaches that the effect the above Example 1 treatment with U.S. No. 6 screen is as follows:
Corn hulls from a wet milling operation contain relatively large amounts of impurities in admixture with the fibrous, relatively large corn hull fraction. These impurities are in the form of ‘fine material' and contain the predominant amount of non-fibrous substances, such as starch, protein, oil containing material, lignified tip cap, etc. Initial separation of such from the corn hulls will result in increased purity of the cellulose, the hemicellulose and the noncarbohydrate fractions. Separation may be accomplished by any convenient method, for instance, by screening through a screen of No. 6 U.S. Standard mesh.
Antrim at col. 2, lines 15-27 (emphasis added). The above cited text of Antrim Example 1 teaches separation of the “fine material” or “fine fiber” (which contains some fatty acids and fatty acid esters) from the corn hulls, and thus some of the fatty acids and fatty acid esters will be separated from the corn hulls. But, although the fines have been separated from the corn hulls (as can be inferred from Antrim and as taught by Moreau), fatty acids and fatty acid esters still remain in the corn hulls themselves and would thus necessarily be present in Antrim’s Example 1 slurry during the extraction with sodium hydroxide.
One of ordinary skill would be well aware that some fatty acids and fatty acid esters still remain in the corn hulls themselves and would thus necessarily be present in Antrim’s Example 1 slurry during the extraction with sodium hydroxide based on the teachings of Moreau. Moreau teaches that corn hulls (from a wet milling operation contain): (1) the corn hulls themselves; and (2) a fine material or fine fiber fraction. For example, Moreau teaches:
During the conventional wet milling of corn, the fibre fraction (sometimes called white fibre) contains both 'fine fibre' derived from the endosperm (inner cellular fibre), and 'coarse fibre'. The coarse fibre is mainly the hull and is comprised of both pericarp and aleurone layers. The pericarp lacks cellular structure and ultrastructurally appears to be almost entirely composed of cell-wall materials. The aleurone layer in corn consists of a single layer of living cells, with thick cell walls. In the current study, corn kernels were steeped in aqueous sulphur dioxide and lactic acid under conditions comparable with those of the steeping step of wet milling, and then the hulls were removed and hand dissected to yield pericarp and aleurone layers. The separated pericarp and aleurone fractions were ground and extracted with hexane and the yields and compositions of the resulting oils were examined.
Moreau 2 at paragraph bridging pages 803-804 (emphasis added).
This teaching of Moreau is summarized by the Examiner as follows:
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Moreau at paragraph bridging pages 803-804. Moreau teaches that corn hulls were wet milled and the fiber, germ, aleurone and pericarp layers were separated and dried, which is summarized by the Examiner as follows:
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Moreau at page 804, col. 1.
Moreau teaches that each of the four separated portions were extracted with hexane and the hexane removed to give an oil extract, summarized by the Examiner as follows.
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Per Table 2 summary of the GC analysis, Moreau teaches that the aleurone extract (inner layer of the corn hull) as well as the germ and fiber extract all contained roughly equal amounts of linoleic and oleic acids. See Moreau 2 at page 805, Table 2.
In summary, Antrim Example 1 teaches separation of fines from corn hulls (from wet milling) by wet screening. The fines will have some oils, and so, Antrim will have accomplished (as he states) separation of some of the oils from the corn hulls. However, a prima facie case has been made that the corn hulls themselves, which Antrim further processes in Example 1 by sodium hydroxide extraction, will also and necessarily also contain oils (oleic acid and linoleic acid) as evidenced by Moreau and as alluded to by Antrim himself. These oils will be extracted into the Antrim Example 1 non-carbohydrate fraction, which one of ordinary skill is motivated to remove in order to arrive at purer ferulic acid. Applicant has not rebutted the prima facie case that oleic acid and linoleic acid are present in Antrim’s liquid extraction product, which as discussed above, one of ordinary skill is motivated to remove. MPEP § 2112(V) (citing In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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ALEXANDER R. PAGANO
Examiner
Art Unit 1692
/ALEXANDER R PAGANO/Primary Examiner, Art Unit 1692
1 There is a presumption that steps of a method claim are not required to occur in the order they are listed that can be overcome when logic or grammar requires that the steps be performed in the order written, or the specification directly or implicitly requires an order of step. Telit Cinterion Deutschland GmbH v. 3G Licensing, S.A., No. 2023-1497, 2025 BL 33256, at *3 (Fed. Cir. Feb. 3, 2025).
2 The following references evidence (as well known in the art MPEP § 2144.03) that compounds with carboxylic acid functional groups are soluble in basic aqueous media. N.G. Anderson, Practical Process & Research Development 203-267, (2000) (“Anderson”) (see page 212 stating “An acidic product may be purified by extraction into a basic aqueous phase to remove basic and neutral impurities, followed by acidification of the rich aqueous phase and extraction into an organic solvent.”); see also, B. Furniss et al., Vogel’s Textbook of Practical Organic Chemistry 162-163 (1989) (“Vogel”). See Vogel at page 163 which states “[t]he original organic solution from which the basic components have been removed is now extracted with several successive portions of dilute aqueous sodium hydroxide or sodium carbonate solution (1M). Acidic components will be extracted into the aqueous alkaline layer”.
3 Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. MPEP § 2112(V) (citing In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977). This is a procedural burden shifting. The requirement that the prior art necessarily teaches the alleged inherent (functional) element still remains. MPEP § 2112(IV). However, the burden is shifted to Applicant to demonstrate the alleged inherent element is not necessarily present in the cited prior art. Stated differently, when the examiner "has reason to believe" that the prior art reference inherently teaches the limitation, the burden shifts to the patent applicant to show that the functional limitation cannot be met by the prior art reference. MPEP 2112(V), see also, In re Schreiber, 128 F.3d 1473, 1478 (Fed. Cir. 1997); In re Chudik, 674 F. App'x 1011, 1012 (Fed. Cir. 2017) (both citing In re Swinehart, 439 F.2d 210, 212, 58 C.C.P.A. 1027 (C.C.P.A. 1971)).
4 Zhao teaches that ferulic acid in brans is usually linked to cell wall polymers by ester bond through their carboxylic acid group with the hydroxyl of the α-l-arabinosyl side chains of xylans. Zhao at page 309, col. 1. Thus, as with Zhao’s corn bran, one of ordinary skill is readily apprised that Antrim’s NaOH extraction of corn hulls (which include a bran or pericarp layer) to release ferulic acid will also release arabinoxylans (polysaccharides).