DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-10 and 13-20 in the reply filed on 04 October 2025 is acknowledged. The additional election of species of ethanol dehydrogenase and lactate dehydrogenase, filed 23 December 2025 is acknowledged.
The requirements are deemed proper and therefore made Final.
Status of Application
Claims 1-10, 13-20 and 24-26 are pending; Claims 24-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 1-10 and 13-20 are subject to examination on the merits.
Claim 17 is withdrawn as it does not recite the specific claimed species of lactate dehydrogenase negative regulation and positive regulation of ethanol dehydrogenase.
Priority
The instant application is a 371 of PCT/CN2020/134922 filed 09 December 2020 which claims benefit of foreign priority documents CN201911349044.1; CN202010874879.8; and CN20211283377.4 filed 12/24/2019; 08/27/2020 and 11/17/2020, respectively, are acknowledged. Said documents have been received.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 17 June 2022 has been considered by the examiner. See initialed and signed PTO/SB/08’s.
Claim Interpretation
The dependent claims each recite “which is characterized in that”. This will be interpreted the same as “wherein”.
In addition, “ethanol dehydrogenase” is interpreted as an alcohol dehydrogenase, given there is no known enzyme with the name (or EC classification) of “ethanol dehydrogenase”.
Claim Objections
Claims 2-10 and 13-20 are objected to because of the following informalities: each of the claims can be improved with respect to grammar by reciting “The construction method as in claim…”.
Claim 1 is objected to because of the following informalities: the last line has a typographical error and recites “strainsare”.
Claim 1 is further objected because “genetic engineering fungi” in the fourth line is grammatically incorrect and should recite “genetic engineered fungi”, in addition, the conjunction “and” should appear before “compared” in the fourth line.
Claim 2 is objected to because of the following informalities: the second line has a typographical error and recites “fungiare”.
In addition, there should be a comma between “Rhizopus” and “Mucor” in the fourth line.
In addition, the first occurrence of Myceliophthora in the fifth line should be italicized.
Claim 7 is objected to because of the following informalities: the second line has a typographical error and recites “geneScahd1”.
Claim 14 is objected to because of the following informalities: the second line has a typographical error and recites “dehydrogenaseScADH1”.
Claim 19 is objected to because of the following informalities; said claims comprises and extraneous period, e.g. an entire new sentence. This can be remedied by replacing the period with a semi-colon or comma and changing “The” to “the”.
Appropriate corrections are 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.
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 3 and 4 are indefinite because they recite the limitation “shuttle pathway of cytoplasmic reducing force to mitochondria” which is not a recognized scientific term or pathway. Thus, it is also unclear what potential genes may or may not be involved with this pathway.
Claim 4 recites the limitation "the genetically engineered fungi with the shuttle of cytoplasmic reducing force to mitochondria is reduced or blocked and/or the byproduct pathway……and/or the transport of sugar molecules……… and/or the glycolysis rate" in reference to claim 1. There is insufficient antecedent basis for the limitations that are italicized because claim 1 does not recite any of the elements.
Claims 5, 7, 9-10, 13-16, 18-19 are indefinite because they recite the enzyme “ethanol dehydrogenase” which is not a recognized scientific term, e.g. there is no enzyme with this name nor any enzyme having an EC number with this term. As noted above, ethanol dehydrogenase will be interpreted as alcohol dehydrogenase (EC 1.1.1.1).
Claim 6 recites the limitation "the introduction is to transfer the expression vector" in reference to claim 1. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not recite any of the elements.
In addition, claim 6 is further rejected as indefinite because the recitation of the phrase "the preferred promoters…….." renders the claim(s) indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 7 recites the limitation "one of the ethanol dehydrogenase coding gene……." in reference to claim 1. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not recite any ethanol dehydrogenase coding genes.
In addition, claim 7 is further rejected as indefinite because the recitation of the phrase "the preferred ethanol dehydrogenases are…….." renders the claim(s) indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 14 recites the limitation "the filamentous fungi overexpressing the ethanol dehydrogenase ScADH1 is from…….and ZmADH1 is from…." in reference to claim 5. There is insufficient antecedent basis for this limitation in the claim because claim 5 while it does recite ethanol dehydrogenase coding genes; it does not recite the specific ethanol dehydrogenases as currently claimed.
Claim 14 is further deemed indefinite because the ethanol dehydrogenase gene to be knocked out/down regulated is “Mtadh”; however, the gene for acetaldehyde dehydrogenase is also “Mtadh”.
Claims 18-20 are rejected as lacking antecedent basis because claim 18 recites the limitation "overexpression of ethanol synthesis gene containing mitochondrial localization signal sequence….overexpression of acetaldehyde dehydrogenase" in reference to claim 5. There is insufficient antecedent basis for these limitations in the claim because claim 5 while it does recite ethanol dehydrogenase coding genes there are no signal sequences associated with them. In addition, claim 5 does not recite acetaldehyde dehydrogenase.
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.
Claims 1-10, 13-16 and 18-20 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains 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 at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a method of genetic engineering filamentous fungi, wherein said fungi overexpress the positive regulation genes of ethanol synthesis, and/or down regulate the expression of the negative regulation genes of endogenous ethanol synthesis to obtain genetic engineering fungi, compared with the original strain, the ethanol synthesis ability of the genetically engineered strains are improved. Thus, the genus of modified genetic engineered fungi is absolutely enormous, having upstream, downstream modifications in the ethanol synthesis pathways by making changes (any number and kind) to those genes which down regulate or upregulate ethanol synthesis, are involved in glycolysis, adding signal sequences genes, improve sugar transport by adding exogenous genes deleting extraneous ones, etc, etc. etc. Thus, the genus claimed genetically engineered fungi with improved ethanol synthesis abilities is variable, huge, unpredictable at times and exceedingly diverse. The specification, however, only describe the following: (a) overexpression of exogenous S. cerevisiae alcohol dehydrogenase (Adh1) in M. thermophila; (b) overexpression of S. cerevisiae pyruvate decarboxylase (pdc1) in M. thermophila; (c) overexpression of N. crassa glucose transporter (glt-1); (d) overexpression of exogenous S. cerevisiae alcohol dehydrogenase (Adh1) in M. thermophila and knock-out of endogenous lactate dehydrogenase-1 and -2 by introduction of cellobiose transporter 1 and 2; (e) knock-outs of lactate dehydrogenase-2 (ldh2) and mannitol 1-phophate dehydrogenase (mpd) in M. thermophila; (f) inactivate malate dehydrogenase in M. thermophila; (g) attenuate cytochrome c oxidase in M. thermophila; (i) knock-out of glycerol-3-phosphate dehydrogenase (gpd); (j) knock-out of endogenous ethanol dehydrogenase and acetaldehyde dehydrogenase in M. thermophila; (k) knock-out of phosphofructokinase-2 in M. thermophila; (l) overexpression of Thermoanaerobacterium saccharolyticum acetaldehyde dehydrogenase (adhE), S. cerevisiae alcohol dehydrogenase (Adh1) and S. cerevisiae pyruvate decarboxylase (pdc1) in M. thermophila. These 12 examples, however, are not representative of all the potential upstream, downstream, substitutions, knock-outs, insertions, attenuations, etc. that are currently encompassed by the claims for overexpressing positive regulation genes of ethanol synthesis, for example, any involved in ethanol synthesis pathway, improving the sugar transport capacity, accelerating the glycolysis rate, improving cytoplasmic reducing power and containing mitochondrial localization signal sequence, or those genes indirectly impacting any genes in these pathways. Or wherein the down regulating the expression of the negative regulation genes of endogenous ethanol synthesis, for example, any of the genes in the branch pathway of ethanol synthesis, the shuttle pathway of cytoplasmic reducing force to mitochondria, the endogenous ethanol metabolism pathway and the electron transfer chain (respiratory chain), or those genes indirectly impacting any genes in these pathways. This is in addition to the numerous strains/species/genus of genetically engineered filamentous fungi being claimed, wherein only M. thermophila is described in the specification. Li et al. (Biotech. Biofuels, 2020 – cited on IDS) teach no other thermophilic filamentous fungi has been genetically engineered to produce or overproduce ethanol. While modifying other microorganisms such as yeast (S. cerevisiae) or prokaryotes such as E. coli are common and known in the art, the genus of claimed modifications is enormous and extensive and not always predictable across all filamentous fungi. Even for the modifications made herein to M. thermophila it is clearly unpredictable because certain modifications only produced greater ethanol production when grown on certain carbon sources. As such, the claimed genus of genetically engineered filamentous fungi with an enormous number of modifications therein that may positively impart greater ethanol production, far exceeds that which is described and supported in the specification.
The MPEP in section 2163(I) states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonable conclude the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
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An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)"
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-10 and 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (Biotech. Biofuels, 2020 – cited on IDS).
It is noted, the earliest filed foreign priority document does not have a certified English translation to establish support for the current claims, as such, Li et al. currently applies as prior art.
Li et al. teach:
A method of modifying the thermophilic filamentous fungus M. thermophila by introducing S.cerevisiae alcohol dehydrogenase ADH1 into said fungus; then introducing four copies of N. crassa glucose transporter GLT-1; followed by further introduction of N. crassa cellodextrin transporters CDT-1/-2 into the two loci for the endogenous lactate dehydrogenases; additional deletions were in the gene aep wherein the targeting was accomplished via CRISPR Cas9 utilizing sgRNA to target said genes; and finally, attenuating endogenous pyc expression – See Materials and Methods and “Engineering of M. thermophila to produce ethanol from cellobiose”, pp. 5-7.
Claim(s) 1-7, 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (Direct Microbial Conversion of Biomass to Advanced Biofuels, Chapter 11, 2015 – cited herein).
Xu et al. teach genetic engineering of the filamentous fungus Trichoderma reesei for enhanced ethanol production by introducing an expression vector comprising S. cerevisiae alcohol dehydrogenase (ADH1) and S. cerevisiae pyruvate decarboxylase (PDC1), and overexpressing these two enzymes resulting in enhanced ethanol production compared to the strain not expressing these enzymes – See pp. 203-206.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 10 March 2026