DETAILED ACTION
Status of Application
Claim 2 is cancelled, thus, claims 1, 3-10, 13-20 and 24-26 remain pending; Claims 24-46 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.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, 3-10 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Claim 17 is withdrawn as it does not recite the specific claimed species of lactate dehydrogenase negative regulation and positive regulation of ethanol dehydrogenase.
Withdrawal of Previous Objections/Rejections
Claim Objections
The objection to claims 2-10 and 13-20 due to grammar is withdrawn in view of the amendments to recite “The construction method as in claim…”.
The objection to claim 1 for a typographical error (“strainsare”) is withdrawn in view of the amendment to the claim and the amendment to recite “genetic engineered fungi”.
The objections to claim 2 are withdrawn in view of the cancelation of said claim.
The objection to claim 7 for a typographical error is withdrawn in view of the amendment to correct it.
The objection to claim 14 for a typographical error is withdrawn in view of the amendment to correct it.
The objection to claim 19 is withdrawn in view of the amendment to remove the extraneous period and then recite “the”.
The rejection of claims 3 and 4 under 35 U.S.C. 112(b) for the limitation “shuttle pathway of cytoplasmic reducing force to mitochondria” which is not a recognized scientific term is withdrawn in view of the amendments to delete said phrase.
The rejection of claim 4 for lack of antecedent basis for the term "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byproduct pathway……and/or the transport of sugar molecules……… and/or the glycolysis rate" in reference to claim 1 is withdrawn in view of the amendments to remove the italicized phrase.
The rejection of claims 5, 7, 9-10, 13-16, 18-19 under 35 U.S.C. 112(b) as indefinite because they recited the enzyme “ethanol dehydrogenase” which is not a recognized scientific term is withdrawn in view of the amendments to recite “alcohol dehydrogenase”.
The rejection of claim 6 for lack of antecedent basis for reciting the limitation "the introduction is to transfer the expression vector" in reference to claim 1 is withdrawn in view of the amendments to recite “an expression vector”. In addition, the rejection of said claim for reciting “preferred promoters” is withdrawn view of the amendment to remove the noted phrase of “preferred”.
The rejection of claim 7 for lack of antecedent basis for reciting "one of the ethanol dehydrogenase coding gene……." in reference to claim 1 is withdrawn in view of the amendment to remove “the” before “alcohol dehydrogenase”. In addition, the rejection of said claim for reciting “preferred promoters” is partially withdrawn view of the amendment to remove the noted phrase of “preferred”.
The rejection of claim 14 for lack of antecedent basis for recitation of "the filamentous fungi overexpressing the ethanol dehydrogenase ScADH1 is from…….and ZmADH1 is from…." in reference to claim 5 is withdrawn in view of the amendments to remove “the” prior to “alcohol dehydrogenase”.
The rejection of claims 1-10 and 14-16 under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (Biotech. Biofuels, 2020 – cited on IDS) is withdrawn in view of the submission of a certified English translation of the foreign priority document. Li et al. was an intervening reference but is not longer applicable as prior art.
The rejection of claim(s) 1-7, 14-16 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 previously) is withdrawn in view of the amendments to the claims to require the filamentous fungi that are engineered are Myceliophthora thermophila or M. heterothalica.
Maintained Rejections
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.
Claim 7 is rejected under 35 U.S.C. 112(b) as 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.
Said claim still recites “the preferred pyruvate decarboxylases are….”
Applicant’s responded to this rejection but appear to have overlooked the last “preferred” part of the claim.
Claim 14 is rejected under 35 U.S.C. 112(b) as 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 14 is deemed indefinite because the ethanol dehydrogenase gene to be knocked out/down regulated is “Mtadh”; however, the gene for acetaldehyde dehydrogenase is also “Mtadh”. It is unclear how two different enzymes are encoded by the same Mtadh gene.
Applicant’s have not responded to this section of the recjection.
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.
Applicant’s Response and Examiner’s Rebuttal:
Applicant’s assert that by changing “ethanol dehydrogenase” to “alcohol dehydrogenase” overcomes both problems with the claims.
However, it does not overcome the antecedent issue of recitation of “signal sequences” with reference to claim 5 as “signal sequences” are never mentioned. In addition, “acetaldehyde dehydrogenase” is also not mentioned in claims 5 or 1 and thus lacks antecedent basis.
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 of the species Myceliophthora thermophila or M. heterothalica, 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 modifications being made to the 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. 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.
Applicant’s Response and Examiner’s Rebuttal:
Applicant’s have addressed only one aspect of the written description rejection, namely, the variability of modified recombinant fungi is now Myceliophthora thermophila or M. heterothalica. However, this does not address the huge variability of potential modifications in the 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. The variability and predictability of the required changes to produce the requisite function is enormous and the limited examples, as outlined above in the rejection do not fully represent the claimed genus. As such, the rejection is maintained.
Conclusion
No claim is allowed.
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.
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 27 July 2026
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