DETAILED ACTION
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 .
Status of the Claims
Claims 1-20 are pending and are rejected.
Priority
This application is a 371 of PCT/US2021/064132, filed 12/17/2021, which claims priority to EP 20215448.0, filed 12/18/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/31/2023 is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Accordingly, the IDS has been considered by the examiner and a signed copy is enclosed herewith.
Claim Objections
Claims 2, 12, 14 and 17 are objected to because of the following informalities:
Claim 2, step (g), recites “100ºC”, which is missing a space between the number 100 and the degrees centigrade (i.e., 100 ºC).
Claim 12, line 2, recites “4-tert-Butylphenyl boronic acid,” which is grammatically incorrect, because butyl is capitalized.
Claim 14, line 2, recites “cresol (m),” which is a misspelling of “m-cresol.
Claim 14, line 4, recites “2,6 xylenol,” which is missing a hyphen.
Claim 14, line 4, recites “4Et-phenol,” which is grammatically incorrect. The following is suggested: 4-ethylphenol.
Claim 14, line 6, recites “an any” which is a misspelling of “and any”.
Claim 17 recites “nMe-acetamide” and “nMe-pyrrolidine,” which are grammatically incorrect. The following is suggested: “N-methylacetamide” and “N-methylpyrrolidine”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-20 are rejected under 35 U.S.C. 112(b) being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1, step (b), recites the broad limitation “boronic acid” and also recites the narrower limitation “BA: R-B(OH)2”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim is considered indefinite because there is a question or doubt as to whether the boronic acid introduced by the narrower language in parentheticals is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claims 3-11 and 13-20 depend from claim 1 and inherently contain the indefinite broad/narrow limitation, these dependent claims are indefinite.
Claim 1, step (f), requires “a ratio of conversion solution to the non-aqueous phase in a range from 0.1 to 10.0 by weight.” The 0.1 to 10.0 range is not presented as a ratio. Therefore, the precise ratio range is unclear. The specification (e.g., ¶ 96) repeats the same range, and recites additional ranges (e.g., “from 1 to 3”) without further clarification. Claims 3-20 depend from claim 1 and inherently contain the indefinite ratio limitation, these dependent claims are indefinite.
For the purposes of applying prior art, the claimed weight ratio range will be construed as 0.1:1 to 10.0:1.
Claim 2, step (b), recites the broad limitation “boronic acid” and also recites the narrower limitation “BA: R-B(OH)2”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim is considered indefinite because there is a question or doubt as to whether the boronic acid introduced by the narrower language in parentheticals is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 2, step (f), requires “a ratio of conversion solution to the non-aqueous phase in a range from 0.1 to 10.0 by weight.” The 0.1 to 10.0 range is not presented as a ratio. Therefore, the precise ratio range is unclear. The specification (e.g., ¶ 96) repeats the same range, and recites additional ranges (e.g., “from 1 to 3”) without further clarification.
Claim 9 depends from claim 1 and refers to the limitation “the distillation bottom product”, which lacks antecedent basis in the claims. Claim 9 requires a portion of the second aqueous phase from (h) to contain “the distillation bottom product comprising water-insoluble solvent and water-insoluble boronic acid.” The second aqueous phase from (h) comprises “water-insoluble solvent, water-insoluble boronic acid, and furfural” according to claim 1. However, no distillation step preceded formation of the second aqueous phase, so the “the distillation bottom product” limitation does not inherently have antecedent basis in the claims. Since the limitation lacks antecedent basis, the claim is indefinite.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over:
Griffin ”Solvent extraction and purification of sugars from hemicellulose hydrolysates using boronic acid carriers.” J. Chem. Technol. Biotechnol. 2004, 79, 505−511
as evidenced by
Gori “Isolation of C5-Sugars from the Hemicellulose-Rich Hydrolyzate of Distillers Dried Grains” ACS Sustainable Chem. Eng. 2015, 3, 2452−2457, and further evidenced by
CAS STN database (online), RN 32316-92-0 [Entered STN: Nov. 16, 1984], and
ICSC database (online), Isodecyl alcohol, ICSC: 0495 (October 1999), Retrieved on Sept. 4, 2026 from https://chemicalsafety.ilo.org/dyn/icsc/showcard.display?p_card_id=0495;
in view of
Marcotullio “Chloride Ions Enhance Furfural Formation from D-Xylose in Dilute Aqueous Acidic Solutions.” Green Chem. 2010, 12, 1739−1746,
Alipour WO 2015066287 A1 and
Raines WO 2013049424 A1.
Griffin teaches claimed steps (a)-(d). “[F]ive types of boronic acids (see Fig 1) dissolved in an organic diluent [] containing the quaternary amine Aliquat 336 were screened for their ability to extract sugars (fructose, glucose, sucrose and xylose) from a buffered (pH 11), immiscible aqueous solution. Trials were then conducted to extract xylose and glucose from solutions derived from the dilute acid hydrolysis of sugar cane bagasse [].” Griffin 506 (right column). “[S]amples of an aqueous, buffered [] solution containing 10 mM of the sugars fructose, glucose, sucrose and [xylose][] were mixed with an equal volume of organic solution composed of a diluent (Exxal 10 or Shellsol 2046) containing 150 mM Aliquat and 0, 30, 50 or 70 mM of a boronic acid extractant,” such as naphthalene-2-boronic acid (N2B). Griffin 507 (right column). See also Fig. 2. In another example, “[s]ugar concentrations in hydrolysate feed = 0.79 g dm-3 glucose and 9.4 g dm-3 xylose,” were mixed with a solution comprising 150 mM
N2B. See Fig. 3.
PNG
media_image1.png
276
756
media_image1.png
Greyscale
“The organic phase solutions were composed of the diluent Exxal 10 [], an industrial solvent composed primarily of isodecyl alcohol [], or Shellsol 2046 [], an industrial diluent composed of 200 g kg−1 aromatics and 800 g kg−1 naphthenes and paraffinics.” Griffin 507 (left column). “The extraction and stripping processes appear to have been highly selective towards the transport of sugars [] (see last column of Table 2).” Griffin 510 (right column).
Griffin discloses that the “mechanism of extraction” involves formation of “an anion complex”,
PNG
media_image2.png
83
295
media_image2.png
Greyscale
, between an ionized boronic acid and a sugar molecule in the organic phase. Griffin 506 and Scheme 2.
Griffin uses centrifuge “to separate the two phases” and recovers xylose from the organic phase. Griffin 507. “The resultant loaded organic phase contained 0.63 g dm-3 glucose and 6.1 gdm-3 xylose. The organic phase was then mixed with an equal volume of an aqueous HCl solution (strip solution) that stripped the sugar [] with complete recovery of the sugars being obtained using a strip solution containing >0.3M HCl.” Griffin 509. See also Table 2, showing the results of 1M and 2M HCl strip solutions on xylose recovery.
Compared to the claims, although Griffin teaches steps (a)-(d) as outlined below, Griffin is silent regarding formation of the xylose-diboronate ester (XDE) of step (d); however, the XDE intermediate is inherently formed in Griffin’s process as evidenced by Gori.
Claim 1
Griffin
step (a)
providing an aq. xylose-containing solution comprising ≥ 0.5 wt.% xylose
hydrolysate feed (i.e., aq. buffered solution) comprising 9.4 g dm-3 xylose” (e.g., Fig. 3),
wherein (9.4 g/dm3 = 9.4 g/L = (9.4g/1000 x 100) = 0.94 wt%
step (b)
providing an extraction solution comprising a water-insoluble boronic acid and a water-insoluble solvent
organic solution comprising 150 mM N2B and “slightly polar,” “organic diluent” Exxal 10 (e.g., Fig. 3 and p. 508 left column)
step (c)
combining the xylose solution with the extraction solution,
wherein the ratio of boronic acid to xylose
is > 1: 1 molar and the combined solution
comprises an aqueous phase and a non-aqueous phase,
non-aq. phase comprises xylose-diboronate ester
hydrolysate mixed with an “equal volume of organic solution” (e.g., p. 507)
where the ratio of boronic acid to xylose is
150:62.6 = 2.4:1 (e.g., Fig. 3)
9.4 g/L/150.13 g/mol =0.0626 mol/L = 62.6 mmol
forms “an anion complex” (Scheme 2), which inherently converts to the claimed intermediate, as evidenced by Gori (“diboronic ester adducts”) (e.g., Gori 2453 and Fig. 4).
step (d)
separating a portion of the first non-aqueous phase from the first combined solution
separating the phases by centrifuge (e.g., Griffin 507)
Gori teaches “a process for isolation of crystalline D-xylose [] from distillers dried grains (DDG) hydrolyzate that exploits the boronic acid affinity for cis-diols [] [via] toluene extraction of diboronic ester adducts formed on treatment of the hydrolyzate with phenylboronic acid (PBA).” Gori 2453. See also Figure 4, shown in part below:
PNG
media_image3.png
680
705
media_image3.png
Greyscale
Marcotullio teaches claimed steps (e)-(g), drawn to using high ionic strength acidic solutions for converting xylose to furfural “at temperatures between 170 and 200 ºC” (Marcotullio 1744 right column). “[W]ith increasing chloride salts concentration, xylose reacts significantly faster to furfural, while no significant effect is observed on the side reactions, resulting in a remarkable selectivity improvement.” Marcotullio 1743, right column. “[S]uch double catalytic effect can seemingly be achieved by the addition of metal chlorides to aqueous acidic solutions, allowing for high furfural yields and relatively high xylose reaction rates… [A] 4-fold xylose reaction rate increase was possible by 1.7 M NaCl addition keeping the acid concentration as low as 50 mM (0.18 wt% HCl).” Marcotullio 1744, right column. “Xylose concentration for every experiment was 35 mM.” Marcotullio 1745, left column.
Claim 1
Marcotullio (in view of Griffin)
step (e)
providing a conversion solution at a pH of ≤ 4, comprising a water-soluble solvent and water
solution comprising 1.7 M NaCl and “as low as”
50 mM aq. HCl (e.g., p. 1744; HCl = solvent)
(50 mM = 0.050 M; pH = − log10(0.05) = 1.30)
step (f)
combining a portion of the non-aqueous phase from (d) with the conversion solution in a weight ratio of 10:1 to 0.1:1 to form a second solution
Modifying Griffin—wherein the “organic phase” comprising xylose-boronate (i.e., XDE as evidenced by Gori) is combined with “an equal volume” of aq. HCl “strip solution” (Griffin 509)—by using Marcotullio’s HCl solution (e.g., 1744) as the “strip solution” in Griffin’s process.
“equal volume” suggests a 1:1 wt ratio of solutions
step (g)
heating the second combined solution to a temperature Th creating a homogeneous liquid phase and converting a portion of the xylose-diboronate ester into furfural
converting xylose (via XDE in view of Griffin, as evidenced by Gori) to furfural “at temperatures between 170 and 200 ºC” (e.g., p. 1744)
(homogenous characteristics being inherent since the process is the same)
Alipour teaches claimed steps (h)-(i), drawn to cooling, separating and recovering furfural from a non-aqueous (organic) phase. Alipour teaches an advantageous method of converting xylose to furfural that eliminates a xylose-isolation step; the method comprising:
- treating a ketose mixture with an aryl boronic acid “complexing agent (CA)” in a “first immiscible phase,” comprising a liquid such as octanol to form a xylose-conjugate,
- stripping xylose from the conjugate using an HCl solution at pH 1-5 (i.e., “a second immiscible phase”), contacting the solution with a “third immiscible phase” comprising, for example, methyl isobutyl ketone (MIBK), and
- heating and dehydrating the xylose-HCl-MIBK solution in DMSO to produce furfural, followed by flash evaporation/distillation to remove water/MIBK. See, e.g., Alipour ¶ 6-7, 10-11, 14 and 19-20. In the last step of the process, furfural is distilled and the process streams are recycled. See ¶ 37 and Fig. 9b, shown in part below:
PNG
media_image4.png
424
718
media_image4.png
Greyscale
Claim 1
Alipour ( in view of Marcotullio + Griffin)
step (h)
cooling the second combined solution comprising:
(i) second aqueous phase comprising water, water-soluble solvent, and furfural and
(ii) second non-aqueous phase comprising water-insoluble solvent, water-insoluble boronic acid, and furfural; and
separating the second non-aqueous phase from the cooled second combined solution
cooling the dehydrated xylose solution comprising:
(i) water, HCl, DMSO (water-sol. solv.) and furfural
and
(ii) MIBK, DMSO, aryl boronic acid and furfural
(DMSO and furfural are polar aprotic molecules with solubility in both the aqueous and organic phases)
separating the phases via flash evaporation/distillation
(e.g., ¶ 19, 20, 37 and Fig. 9b)
step (i)
recovering furfural in the second non-aqueous phase
further separation of the organic phase (comprising residual water) by distillation results in recovering furfural (e.g., Fig. 9b)
The claimed process would have been obvious because a PHOSITA would have been motivated to convert xylose to furfural using Marcotullio’s extraction process after conducting the xylose complexation with boronic acids according to Griffin’s process. The combined process provides the advantage of skipping the sugar drying step and going directly to furfural from a xylose extraction solution, as well as the advantage of “high furfural yields and relatively high xylose reaction rates” according to Marcotullio (discussed above). A PHOSITA would have had a reasonable expectation of success in combining the two methods, because Alipour successfully applied modified the processes of Griffin (boronic acid treatment of biomass hydrolysates comprising xylose) and Marcotullio (extraction of xylose) to the conversion of xylose to furfural.
Further evidence that a PHOSITA would have had a reasonable expectation of success is supported by Raines, which teaches success with using a boronic acid and metal ion for converting xylose to furfural. (“The pyranose sugars galactose and mannose and the furanose sugars sorbose and tagatose, were converted to HMF using the 2-substituted phenylboronic acid in the presence of magnesium ion and water in both a polar aprotic solvent other than an ionic liquid (e.g., DMA) and ionic liquid (e.g., [EMIM]Cl.) Pentose sugars (xylose and arabinose) are converted under analogous reaction conditions to furfural.” Raines 34.)
In addition, a PHOSITA would have been guided to the claimed cooling, separating and recovering steps in view of Alipour’s teaching of an advantageous method for converting xylose to furfural that eliminates a xylose-isolation step. See, also, Alipour Fig. 12 (“a comparative technoeconomic evaluation of furfural production by direct xylose dehydration” ¶ 40). Therefore, the process of claim 1 would have been obvious to a PHOSITA.
Claim 2 contains additional limitations compared to claim 1 pertaining to step (g), namely heating to a temperature 100 ºC. This temperature is disclosed by Marcotullio’s heating step “at temperatures between 170 and 200 ºC” (e.g., Marcotullio 1744).
Claim 3 further limits step (i) by requiring “providing at least a portion of the second non-aqueous phase from (h) to a distillation process to recover an overhead product comprising furfural and a bottom product comprising water-insoluble solvent and water-insoluble boronic acid.” Claim 4 depends from claim 3 and further requires “providing at least a portion of the bottom product for use as part of the extraction solution.” Claim 9 encompasses a combination of the limitations of claims 3 and 4. All of these limitations are taught or suggested by Alipour’s distillation process of Fig. 9b and the recycling process of Fig. 1, for example. (“The stripped aldose and the organic phase are recycled and reused” ¶ 27.) (“[P]rovided herein are examples of how these sugars can be converted to furans in high yields through such processes [] permitting recovery and reuse of the reaction and solvent media” ¶ 49.)
Claim 5 depends from claim 4 and further requires that the first aqueous phase in step (c) (resulting from combining an aqueous, buffered xylose hydrolysate with an “equal volume of organic solution” comprising a boronic acid, according to Griffin, (e.g., p. 507)) “comprises water-soluble solvent, water-insoluble solvent, and water-insoluble boronic acid.” Griffin teaches these limitations to be buffer, Exxal, and N2B, respectively. Claim 5 further requires separating the aqueous phase and recovering a water-soluble solvent, a water-insoluble solvent, or a water-insoluble boronic acid. The recovering steps are taught by Alipour, wherein “process streams” are recycled. See ¶ 37, 50 and Fig. 9b.
Claim 6 is drawn to the method of claim 1 wherein step (c) (combining Griffin’s xylose hydrolysate with boronic acid) and step (d) (separating the resulting phases) are performed in a “liquid-liquid extraction unit in counter-current operation, wherein the xylose-containing solution is provided at a higher temperature than the []extraction solution [temperature].” Griffin teaches this limitation (i.e., “efficient extraction of xylose and glucose from hydrolysate solutions with the potential for almost complete extraction of the sugars by continuous, countercurrent operation.” Griffin 510, right column.
Griffin does not teach the claimed temperature parameters for the countercurrent extraction process (i.e., wherein the xylose solution is at a higher temperature than the extraction solution); however, a PHOSITA would have found it obvious to modify Griffin’s extraction process by optimizing the temperature of the solutions in view of Alipour. Alipour teaches various temperatures are used during the stripping and extraction processes. Alipour ¶ 51 and Fig. 9b, for example. Since temperature was a well-known, result-effective variable impacting the solubility and separation of solutes, a PHOSITA would have found it obvious to optimize the and elevate the temperature of the xylose solution (to increase xylose solubility) compared to the extraction solution to maximize xylose extraction.
Claim 7 depends from claim 1 and further requires distilling the second aq. phase from step (h) and recovering “an overhead product comprising water and furfural and an acidic bottom product” having a pH < 7 and “comprising water and water-soluble solvent.” These limitations are taught by Alipour, which discloses separating the phases via flash evaporation/distillation and recovering the claimed furfural/water products and acidic products comprising water and DMSO (water-soluble solvent). Since the combined phases had a pH=1 and the acid was not neutralized, the separated bottom product would inherently have had a pH < 7. (See e.g., ¶ 19, 20, 37 and Fig. 9b).
Claim 8 depends from claim 7 and requires “providing at least a portion of the acidic bottom product for use as part of the conversion solution.” The “for use” phrase is an intended use limitation that does not change the steps required by the process. Since Griffin in view of Alipour teach providing an acidic bottom product, claim 8 would have been obvious.
Regarding claim 10, Griffin teaches the claimed xylose-containing solution being a hydrolysate (e.g., Griffin Fig. 3).
Claim 11 requires the water-insoluble boronic acid of claim 1 to have a water solubility of ≤ 5 wt.% at 20 ºC. Griffin teaches several boronic acids including 2-napthylboronic acid (a.k.a. N2B), which has a water solubility of 0.03 wt.% at 20 ºC (i.e., ≤ 5 wt.%) according to the specification (¶ 39).
Griffin renders obvious the claimed method of using phenyl boronic acid, 2-naphthylboronic acid and 4-tert-butylphenyl boronic acid of claim 12. E.g., Griffin Fig. 1.
Claim 13 requires the water-insoluble solvent of claim 1 to have a water solubility of ≤ 5 wt.% at 20 ºC. Griffin teaches Exxal 10 as the corresponding water-insoluble solvent, which is predominantly isodecanol. Isodecanol inherently has a water solubility of 2.5 g/100 mL (i.e., 2.5 wt.%) according to the ICSC database. Since ICSC is silent regarding the solubility temperature, a PHOSITA would have regarding the data to correspond to room temperature data, for it is conventional to omit the temperature if it is room temperature, according to Official Notice.
Alipour (in view of Marcotullio and Griffin) renders obvious the water-insoluble solvent octanol of claim 14. Alipour ¶ 11. (“In certain embodiments, the first immiscible phase comprises a liquid that is immiscible with the aqueous isomerization reaction mixture and is capable of dissolving the CA. [] [T]he liquid is selected form the group consisting of octanol…”)
The limitations of claim 15 and claim 20 are met by the 2-naphthylboronic acid, taught by Griffin, which has a boiling point of 382±25 ºC, as evidenced by CAS RN 32316-92-0, which is more than 5 ºC higher than the boiling point of furfural. According to the specification, the boiling point of furfural is 162 ºC (spec. ¶ 38).
The water-soluble solvent required by claims 16-19 is taught by Alipour, which discloses DMSO (a water soluble solvent) in a step that corresponds to claimed step (h). DMSO has a logP of -1.35 according to the specification (¶ 61), which falls in the claimed logP range of -3 to 0, and has a boiling point (189 ºC) that is more than 5 ºC higher than water (100 ºC).
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA L AGUIRRE whose telephone number is (571)272-5592. The examiner can normally be reached 10 am-6 pm MST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H MURRAY can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AMANDA L. AGUIRRE/ Primary Examiner, Art Unit 1626
Prosecution Insights