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 1-21 are pending.
The instant claims are entitled to an effective filing date of 02/22/2022.
Election/Restrictions
Applicant’s election, without traverse, of species (2) mutated galactose oxidase (claim 5) for Genus A in the reply filed on 07/08/2026 is acknowledged. The requirement for an election of species from Genus A is withdrawn, such that all species of Genus A are reinstated and will be considered in this action.
Accordingly, claims 1-21 are under consideration in this action.
Specification
The disclosure is objected to because of the following informalities:
The specification recites GDA in paragraphs [0012], [0018], [0019], [0075], [0076], [0077], [0078], [0079], [0081], [0082], [0083], and [0085], but does not define GDA.
Appropriate correction is required.
Claim Objections
Claim 6 and 15 are objected to because of the following informalities:
Claim 6 recites “SEQ ID No.1 through SEQ ID NO.:9”, which should be replaced with the proper sequence identifiers “SEQ ID NO: 1 through SEQ ID NO: 9”.
Claim 15 recites “SEQ ID No.7 through SEQ ID No.:9”, which should be replaced with the proper sequence identifiers “SEQ ID NO: 7 through SEQ ID NO: 9”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor, at the time the application was filed, had possession of the claimed invention.
Claims 1-13 are drawn to a genus of combinations of biocatalysts and dehydration catalysts, where the one or more biocatalysts can be contacted with glucose under conditions suitable for the formation of D-glucodialdose, and the dehydration catalysts can be present during a thermal treatment of D-glucodialdose for the formation of any polyhydroxybenzene. Claims 1-2, 8, and 10-13 do not limit the structure of the biocatalyst or the dehydration catalyst in anyway. Claims 3-7 limit the biocatalyst structure, but do not limit the dehydration catalyst. Claim 9 limits the dehydration catalyst but does not limit the biocatalyst. Therefore, claims 1-13 do not substantially limit the genus of biocatalyst and dehydration catalyst combinations.
Claims 14-21 are drawn to a genus of dehydration catalysts that can be present during a thermal treatment of D-glucodialdose for the formation of any polyhydroxybenzene. Claims 14-21 do not limit the structure of the dehydration catalyst in anyway.
The specification does not disclose a representative number of species of the claimed genus of biocatalyst and dehydration catalyst combination by reduction to practice; nor does the specification disclose a representative number of species of the claimed genus of dehydration catalysts by reduction to practice. Furthermore, the specification does not provide adequate guidance with regard to the structural features of the genera that are required to provide the recited properties. Therefore, one of skill cannot immediately envision which biocatalyst and dehydration catalysts will have the required functional characteristics, and one could not conclude that Applicant was in possession of the claimed genera at the time the filing, as discussed more fully below.
For claims drawn to a genus, MPEP § 2163(3)(a)(ii) indicates the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics, i.e., structure or other physical and/ or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The instant specification reduces to practice one example of a biocatalyst and two examples of dehydration catalysts. In example 1, the specification teaches reacting the biocatalyst galactose oxidase (GAO) mutant 47 (GAO-Mut47, SEQ ID NO:8) with glucose in the presence of catalase and CuSO-4 (dehydration catalyst) for the production of D-glucodialdose. See [0074]. In example 2, glucose, catalase, horseradish peroxidase, MnSO4 (dehydration catalyst) and GAO-Mut47 are reacted at 11˚C for 48 hours. After the 48h reaction, >95% of glucose is converted to GDA. See [0075]. GDA is heat incubated at temperatures from 40 to 90˚C. Samples are taken and assayed with HPLC to monitor the formation of dehydrated product, 1,2,3,4-tetrahydroxybenzene and other intermediate products. See [0076]. After an incubation time of 24 hrs, the reaction yields the 1,2,3,4-tetrahydroxybenzene as the major product. See [0077].
MPEP 2163(3)(a)(ii) states that “the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation. Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date”. Considering the lack of guidance provided in the specification, one would appraise support from the state of the art to extrapolate the correlation between the biocatalyst structure and function of forming D-glucodialdose from glucose, and the correlation between the dehydration catalyst structure and the function of forming polyhydroxybenzene from D-glucodialdose.
With respect to the state of the art on biocatalysts and dehydration catalysts, Pedersen (Organic Process Research & Development, 2015, 19(11), 1580-1589) discloses that galactose oxidase (GOase) is a promising catalyst for the oxidation of primary alcohols to their corresponding aldehydes. See the abstract. Pedersen suggests that the substrate specificity of wild-type GOase is rather restricted, but a variety of altered substrate specificities for GOases have been reported including novel glucose 6-OH activity. See p. 1581 para. 1. Pedersen discloses that GOases require a number of additives to sustain its catalytic function. See the abstract. Pedersen suggests that these additives include catalase, which provides protection against GOase activity loss by removing H2O2, and through the regeneration of dissolved oxygen to continue alcohol oxidation. See p. 1582 right column first passage. Furthermore, Pedersen suggests that copper is a required additive, because it is a requirement in the active site of GOase. See p. 1585 right column para. 1. However, Pedersen does not disclose whether copper can also act as a dehydration catalyst for the formation of polyhydroxybenzene from d-glucodialdose. Lee (WO 2021/178935; hereafter Lee) teaches that glucose may be contacted with a galactose oxidase (GAO) variant under conditions suitable for oxidation of the C6 alcohol to an aldehyde generating D-glucohexodialdose (also known as D-glucodialdose). See [0040]. Lee teaches dehydration catalysts comprising hafnium, tantalum, zinc or a combination thereof. See [0084]. However, Lee does not disclose whether those dehydration catalysts may be present under conditions suitable for the formation of polyhydroxybenzene from D-glucodialdose. As such, Pedersen, and Lee illustrate the unpredictability in the art of using any biocatalyst for the formation of D-glucodialdose from glucose, and any dehydration catalyst for the formation of polyhydroxybenzene from D-glucodialdose.
In view of the prior art, the instant disclosure does not satisfy the written description requirement because the species disclosed do not adequately represent the substantial variation within the claimed genus. As discussed above, the breadth of potential structures embraced by the claims is substantial. The instant specification reduces to practice one example of a biocatalyst and two examples of dehydration catalysts. This represents a very small fraction of the possible number of species within the breadth of the claims. As evidenced by Pedersen, galactose oxidase can be mutated to accept glucose as a substrate. However, Pedersen also suggests that the activity of galactose oxidase may depend on the presence of additives including catalase and copper. The instant specification discloses that copper and manganese are examples of dehydration catalysts. However, as evidenced by Lee, dehydration catalysts encompass zinc, hafnium, tantalum, which are not disclosed in the instant specification as being capable of acting as a dehydration catalyst for the required formation of polyhydroxybenzene from D-glucodialdose. Consequently, one of ordinary skill in the art could not conclude that Applicant was in possession of the claimed genera at the time the application was filed.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 and 12-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 8, 12-14, and 16-17 recite “about”, which is a term of approximation. The specification does not describe or provide examples of upper and lower limits of the range encompassed by the term “about”. Therefore, one of ordinary skill in the art cannot ascertain the amount of permissible variation. Claims 8 and 14 recite “about 40° C to about 100° C”, which could reasonably be interpreted as encompassing 39-101°C, 10-100°C, 1-200°C, etc. because the specification and the claims do not clearly set forth the metes and bounds of the required range. To obviate this rejection, the term “about” can be deleted from the claims.
Claims 15, and 18-21 depend from claim 14 and are rejected for the reason set forth above.
Claim 21 recites the limitation “the industrial water” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 21 depends from claim 14, which does not require industrial water.
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.
Claims 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Frost (US 2004/0209337, as cited on the IDS filed 05/21/2024) in view of Lee (WO 2021/178935).
Regarding claim 1, Frost teaches a method for the production of 1,2,3,4-tetrahydroxybenzene, comprising: a) incubating, in the presence of a carbon source, a first microbe comprising a recombinant DNA encoding a naturally occurring myo-inositol-1-phosphate synthase and a second microbe which expresses a naturally occurring inositol dehydrogenase to produce myo-2-inosose; and b) converting the myo-2-inosose to 1,2,3,4-tetrahydroxybenzene (i.e. polyhydroxybenzene) by acid catalyzed dehydration. See claim 1 of Frost. The first microbe is an Escherichia coli. See claim 5 of Frost. The carbon source comprises glucose. See claim 11 of Frost. In example 1, Frost teaches a fermentation medium that includes MnCl-2·4H2O, and CuSO-4 ·5H2O (i.e. manganese and copper dehydration catalysts). See [0048]. Cultures are grown at 37˚C. See [0054]. Frost teaches a bioconversion mixture maintained at a temperature of about 30˚C to about 37˚C. See [0032].
Frost does not teach contacting glucose with one or more biocatalysts suitable for the formation of D-glucodialdose.
Lee teaches cloning enzymes into an expression vector and transforming the expression system into cells including E. coli. See [0074]. Lee teaches a galactose oxidase mutant 47 enzyme (GAO-Mut47) (i.e. biocatalyst) that produces D-glucodialdose from glucose. Lee teaches a reaction that is conducted in a vessel with CuSO4, glucose, catalase, horseradish peroxidase, and the engineered GAO. See [0176].
Frost and Lee do not teach thermally treating D-glucodialdose. However, Frost teaches a fermentation medium containing copper and manganese (i.e. dehydration catalysts) (see [0048]) and Frost teaches a 37˚C heat condition (see [0054]).
The instant specification discloses that dehydration and rearrangement of D-glucodialdose to 1,2,3,4-tetrahydroxybenzene may be carried out by subjecting D-glucodialdose to temperatures ranging from about 40° C to about 100° C. See [0038]. Catalysts that facilitate the conversion of D-glucodialdose to 1,2,3,4-tetrahydroxybenzene include metals such as manganese and copper. See [0039].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to transform Frost’s E. coli with Lee’s nucleotide encoding the GAO-Mut47 biocatalyst. One of ordinary skill in the art would have been motivated to do so because Lee teaches preparing high purity oxidation products of glucose (see [0089]). There would have been a reasonable expectation of success because Frost teaches producing 1,2,3,4-tetrahydroxybenzene (i.e. polyhydroxybenzene) by incubating modified E. coli cells with glucose at 37˚C, and Lee teaches a nucleotide encoding GAO-Mut47 that can be expressed in E. coli.
Regarding claim 2, Frost teaches a method for the production of 1,2,3,4-tetrahydroxybenzene. See claim 1 of Frost.
Regarding claim 3, Lee discloses that galactose oxidase is a member of the copper radical oxidase family. See [0048].
Regarding claim 4-6, Lee teaches galactose oxidase having any one of SEQ ID NO: 6-11. See claim 4 of Lee. Lee teaches galactose oxidase mutant 47. See [00176]. Lee’s SEQ ID NO: 8 is identical to instant SEQ ID NO: 8. See the office action appendix for the alignment.
Regarding claim 7, Lee teaches contacting D-glucose with an enzyme selected from the group that includes catalase and galactose oxidase. See claim 1 of Lee.
Regarding claim 8, Frost teaches growing cultures at 37˚C (i.e. about 40˚C). See [0054]. Frost teaches a bioconversion mixture maintained at a temperature of about 30˚C to about 37˚C. See [0032].
Regarding claim 9, Frost, in example 1, teaches a fermentation medium that includes MnCl-2·4H2O, and CuSO-4 ·5H2O (i.e. manganese and copper dehydration catalysts). See [0048].
Regarding claim 10-11, Frost teaches a solution of 1,2,3,4-tetrahydroxybenzene and EtOH, which is added to an aqueous solution and distilled (i.e. recovery and purification). See [0076].
Regarding claim 12, Frost teaches a solution of 1,2,3,4-tetrahydroxybenzene and EtOH, which is added to an aqueous solution and distilled (i.e. purification). See [0076].
Frost does not teach the purity of 1,2,3,4-tetrahydroxybenzene that ranges from about 70% to equal to or greater than about 90%.
Lee teaches glucose oxidation productions that may have a purity greater than about 80%. See [0089].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to adjust the purity of Frost’s 1,2,3,4-tetrahydroxybenzene based on the suggestion of Lee. One of ordinary skill in the art would have been motivated to do so because Lee suggests products with purity greater than about 80%. There would have been a reasonable expectation of success because Frost demonstrates purifying the 1,2,3,4-tetrahydroxybenzene by distillation (see [0076]), and Frost further teaches flash chromatography (see e.g. [0045]), which is another mode of purification.
Regarding claim 13, Frost teaches a 66% isolated yield of 1,2,3,4-tetrahydroxybenzene, which meets the instantly required yield range from about 50% to about 90%. See [0043].
Regarding claim 14, Frost teaches a method for the production of 1,2,3,4-tetrahydroxybenzene, comprising: a) incubating, in the presence of a carbon source, a first microbe comprising a recombinant DNA. See claim 1 of Frost. The first microbe is an Escherichia coli. See claim 5 of Frost. The carbon source comprises glucose. See claim 11 of Frost. In example 1, Frost teaches a fermentation medium that includes MnCl-2·4H2O, and CuSO-4 ·5H2O (i.e. manganese and copper dehydration catalysts). See [0048]. Cultures are grown at 37 ˚C (i.e. heat). See [0054].
Frost does not teach contacting glucose with a mutated copper radical oxidase and catalase under conditions suitable for the formation of D-glucodialdose.
Lee teaches cloning enzymes into an expression vector and transforming the expression system into cells including E. coli. See [0074]. Lee teaches enzymes selected from the group that includes catalase and galactose oxidase. See claim 1 of Lee. Lee discloses that galactose oxidase is a member of the copper radical oxidase family. See [0048]. Lee teaches a GAO-Mut47 (i.e. mutated copper radical oxidase) that produces D-glucodialdose from glucose. Lee teaches a reaction that is conducted in a vessel with CuSO4, glucose, catalase, horseradish peroxidase, and the engineered GAO. See [0176].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to transform Frost’s E. coli with Lee’s nucleotides encoding the GAO-Mut47 biocatalyst (i.e. mutated copper radical oxidase) and encoding the catalase. One of ordinary skill in the art would have been motivated to do so because Lee teaches preparing high purity oxidation products of glucose (see [0089]). There would have been a reasonable expectation of success because Frost teaches modifying E. coli cells to encode enzymes and Lee teaches GAO-Mut47 and catalase enzymes that can be encoded and transformed into E. coli.
Regarding claim 15, Lee teaches galactose oxidase mutant 47. See [00176]. Lee’s SEQ ID NO: 8 (i.e. GAO-Mut47) is identical to instant SEQ ID NO: 8. See the office action appendix for the alignment.
Regarding claim 16, Lee teaches glucose oxidation productions that may have a purity greater than about 80%. See [0089].
Regarding claim 17, Frost teaches a 66% isolated yield of 1,2,3,4-tetrahydroxybenzene, which meets the instantly required yield range from about 50% to about 90%. See [0043].
Regarding claim 18, Frost teaches a fermentation vessel. See [0054].
Frost does not teach a method carried out in a single reaction vessel.
Lee teaches a one-step reaction carried out in a vessel. See [00176].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to carry out the method of Frost and Lee in the single fermentation vessel as suggested by Lee. One of ordinary skill in the art would have been motivated to do so because Lee suggests carrying out a one-step reaction in a vessel. There would have been a reasonable expectation of success because Frost demonstrates inoculating an E. coli colony into a fermentation vessel to be grown 37 ˚C (i.e. about 40˚C) (see [0054]) in the presence of manganese and copper dehydration catalysts (see [0048]).
Regarding claims 19, Frost teaches aqueous 1,2,3,4-tetrahydroxybenzene solution comprised of isolated 1,2,3,4-tetrahydroxybenzene and water (i.e. a pharmaceutically acceptable carrier or dilutant). See [0036].
Regarding claims 20-21, Frost teaches aqueous 1,2,3,4-tetrahydroxybenzene solution comprised of isolated 1,2,3,4-tetrahydroxybenzene and water (i.e. a pharmaceutically acceptable carrier or dilutant). See [0036]. Frost teaches distilled, deionized water. See [0047].
Although Frost and Lee do not explicitly teach industrial water or feed water, the water taught by Frost is structurally indistinguishable from that of industrial water and feed water. MPEP 2112.01(II) states that "products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY C BREEN whose telephone number is (571)272-0980. The examiner can normally be reached M-Th 7:30-4:30, F 8:30-1:30 (EDT/EST).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/K.C.B./ Examiner, Art Unit 1657
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