Prosecution Insights
Last updated: April 19, 2026
Application No. 17/426,827

Means and Methods to Overrule Glucose-Mediated Repression of Respiration in Yeast

Non-Final OA §103§112§DP
Filed
Jul 29, 2021
Examiner
BARRON, SEAN C
Art Unit
1653
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Katholieke Universiteit Leuven K U Leuven R&D
OA Round
3 (Non-Final)
53%
Grant Probability
Moderate
3-4
OA Rounds
3y 8m
To Grant
85%
With Interview

Examiner Intelligence

Grants 53% of resolved cases
53%
Career Allow Rate
323 granted / 605 resolved
-6.6% vs TC avg
Strong +32% interview lift
Without
With
+31.6%
Interview Lift
resolved cases with interview
Typical timeline
3y 8m
Avg Prosecution
68 currently pending
Career history
673
Total Applications
across all art units

Statute-Specific Performance

§101
6.2%
-33.8% vs TC avg
§103
43.6%
+3.6% vs TC avg
§102
16.0%
-24.0% vs TC avg
§112
22.4%
-17.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 605 resolved cases

Office Action

§103 §112 §DP
DETAILED ACTION The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. The after-final submission dated 7/24/2025 was not entered as being non-responsive for the reasons given in the miscellaneous Office Action dated 11/25/2025. Applicant's supplemental submission filed on 1/26/2026 has been entered. Election/Restrictions Newly submitted claim 21 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 21 recites a “means-plus-function” limitation which meets the 3-prong analysis to 35 U.S.C. § 112(f), and so narrows the broadest reasonable interpretation of the scope of the claim to the structure, material, or act described in the specification as performing the entire claimed function and equivalents to the disclosed structure, material or act; see M.P.E.P. § 2184. In this case, the disclosed means for reducing the expression of YLR108C is limited to genetic deletion (see Example 4) (imports SEQ ID NO: 3, see FR 6/04/2025), which is not required by independent claims 5 and/or 16 and so is distinct form the other groups of inventions. See the restriction requirement dated 3/15/2024. Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 21 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention. Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention. Claim 5 link(s) invention I, presently claims 5, 11, and 15, and the new invention presented with the instant reply which is presently claims 5 and 21. The restriction requirement between the linked inventions is subject to the nonallowance of the linking claim(s), claim 5. Upon the indication of allowability of the linking claim(s), the restriction requirement as to the linked inventions shall be withdrawn and any claim(s) depending from or otherwise requiring all the limitations of the allowable linking claim(s) will be rejoined and fully examined for patentability in accordance with 37 CFR 1.104 Claims that require all the limitations of an allowable linking claim will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312. Applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, the allowable linking claim, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Where a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01. Response to Amendments Applicant's amendments filed 1/26/2026 to claim 5 have been entered. Claims 1-4, 6-10, 12-14, and 17 are canceled. Claim 21 has been added. Claims 5, 11, 15, 16, and 19-21 remain pending, of which claims 5, 11, and 15 are being considered on their merits. Claims 16 and 19-21 withdrawn from consideration. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 15 depends from claim 15 and recites YLR108C and YDR132C as alternatives, but claim 5 only recites YLR108C. Therefore, claim 15 fails to limit claim 5 as claim 15 broadens the scope of claim 5. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. 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 5 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over van Dijken (“Kinetics of growth and sugar consumption in yeasts”, published 1993) in view of van den Brink (“New insights into the Saccharomyces cerevisiae fermentation switch: dynamic transcriptional response to anaerobicity and glucose-excess”, published 2008). van Dijken discloses that Crabtree-positive yeasts, i.e. Saccharomyces cerevisiae, immediately produce ethanol and acetate upon transfer from glucose limitation to glucose excess, even under fully aerobic conditions. This so-called 'short-term Crabtree-effect' has been ascribed to the inability of such yeasts to instantaneously enhance their respiration rate. This would leave them unable to completely respire the increased flux of sugar entering the cell (and the glycolytic pathway) as a consequence of the increased extracellular sugar concentration (see section titled “Transient state kinetics of sugar metabolism”, first paragraph). Thereby, van Dijken discloses the association of ethanol production and the inability to respirate during environmental changes in glucose levels, Crabtree-effect. Regarding claim 5, van Dijken discloses that the presence of weak organic acids under certain cultivation conditions results in very high respiration rates in S. cerevisiae (see Abstract and page 349, section titled “Effect of weak organic acids on the glycolytic flux”). Further, in aerobic cultures, the presence of non-metabolizable weak acids results in an enhancement of catabolism (or metabolism of carbohydrates), and specifically benzoic acid can enhance respiration without triggering alcoholic fermentation (see page 349, section titled “Effect of weak organic acids on the glycolytic flux”). Therefore, van Dijken discloses a method to reduce lag time by stimulating respiration in yeast cells. Additionally, van Dijken discloses at high oxygen feeds, glucose metabolism by S. cerevisiae was fully respiratory and as oxygen feed was decreased, alcoholic fermentation and respiration occurred simultaneously (see page 350, col. 2, second paragraph). van Dijken discloses at higher oxygen feeds, the glycolytic flux is preferentially directed towards respiration, thereby lowering ethanol yield. Therefore, van Dijken teaches stimulating respiration by high oxygen feed rates, thereby inherently reducing a lag phase. Regarding claim 5, however, van Dijken does not teach reducing the expression YLR108C in the yeast cells. van den Brink’s general disclosure relates to the capacity of respiring cultures of yeast to immediately switch to fast alcoholic fermentation upon a transfer to anaerobic sugar-excess conditions (see Abstract). The goal of the van den Brink’s study was to investigate the dynamic adaptation of S. cerevisiae to the industrially relevant transition from aerobic, sugar-limited and respiratory growth to fully fermentative (i.e., anaerobic glucose-excess) conditions and to dissect responses to the glucose up-shift and onset of anaerobicity (see Background). Therefore, van den Brink’s general disclosure relates to the lag phase and the respiration of yeast by studying their response to glucose and oxygen depletion. van den Brink’s study observed the initial response to fully fermentative conditions showed quite some overlap with published datasets for glucose pulses to aerobic cultures, including induction of the translational machinery and repression of the respiratory chain and aimed to go beyond the primary response to see how yeast adjusted to its altered growth environment (see page 7, “Secondary response”, first paragraph). van den Brink teaches that under these conditions, regulatory factors involved in regulation of the respiratory chain (HAP2, HAP4 and HAP5) were down-regulated together with their targets (see page 8, col. 2, first paragraph). Further, in an attempt to identify robust 'signature transcripts' that show a consistent response to anaerobiosis, the set of significantly responding genes in this dynamic study was compared with several datasets from glucose pulses and aerobic-to-anaerobic shift experiments. van den Brink teaches that the majority of the anaerobic down-regulated genes had functions related to mitochondrial function or oxidative stress response, of which 13 genes contained a Hap1 or Hap2/3/4/5 binding element (see page 9, “Anaerobic “signature” transcripts”, first paragraph). True "signature" transcripts for anaerobicity both within dynamic and steady state conditions are listed in Table 3, which includes the gene YLR108C (see Table 3). van den Brink teaches that the observed reprogramming of the transcriptome was mostly driven by relief from the glucose-limitation, exemplified by preparation for faster growth (induction of ribosomes, nucleotide biosynthesis and amino acids biosynthesis) and glucose repression of various metabolic pathways (see page 11, col. 1, first paragraph). Therefore, regarding claim 5, in order to reduce fermentative responses and reprogramming of the transcriptome to respond to oxygen depletion, one of ordinary skill in the art would recognize that the van den Brink teaches signature transcripts or genes to investigate to stimulate respiration and reduce lag phase. van den Brink teaches up-regulated and down-regulated genes in response to anaerobic conditions, therefore directly providing a list of genes associated with fermentative conditions and alcohol production. Therefore, an ordinary artisan would be motivated to enhance expression of an activator of respiration and reduce the expression of a repressor of respiration in order to reduce the lag phase by stimulating respiration. Regarding claim 11, the lag phase is an inherent property of yeast culture kinetics/dynamics associated with glucose depletion. When the prior art product seems to be identical except that the prior art is silent as to an inherent function, property, or characteristic, a rejection under 35 U.S.C 103 can be made (See MPEP 2112 III). Given van den Brink is also investigating yeast cultures, the yeast cultures would inherently possess or undergo a lag phase associated with glucose depletion. Regarding claim 5, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify gene expression in yeast cells to enable respiration and reduce lag phase as taught by van den Brink and van Dijken. The ordinary artisan would have been motivated to do so because van Dijken teaches production of ethanol and acetate upon transfer from glucose depletion to glucose excess due to respiratory inabilities, and van den Brink teaches signature transcriptional genes associated with switching from aerobic glucose-limited yeast to anerobic sugar-excess conditions. Therefore, an ordinary artisan with the teachings of van den Brink and van Dijken would select one of the signature transcriptional gene, i.e. YLR108C, associated with respiration as taught by van den Brink and reduce or enhance its expression to overcome or reduce the lag phase and/or Crabtree effect in yeast cells as taught by van Dijken. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over van Dijken and van den Brink, as applied to claim 5 above, and further in view of Matsuyama (US Pub No. 2013/0244243 A1) and DiCarlo (Nucleic Acids Research (2013), 41(7), 4336-4343). The teachings of van Dijken and van den Brink are relied upon as set forth above. Regarding claim 15, van Dijken and van den Brink do not teach chimeric gene expression in yeast cells. Matsuyama’s general disclosure relates to a method for producing an expression product of an exogenous gene in a yeast with superior output regulation of gene expression. Regarding claim 15, Matsuyama teaches genome integration by homologous recombination and genetic recombination using shuttle vectors with E. coli is a method that is used to cause expression of arbitrary exogenous genes in Saccharomyces cerevisiae and other yeasts and the like, and teaches promoters, terminator regions and the like for causing expression of the introduced gene are also incorporated in advance (see para. [0003]). Matsuyama teaches that the yeast gene can be YLR108C (see para. [0011]). Therefore, Matsuyama teaches a method of expressing a chimeric gene construct comprising a promotor and the gene YLR108C, achieving respiratory stimulation. DiCarlo teaches S. cerevisiae comprising constitutive Cas9 expression and transient expression of a gRNA cassette, and with near 100% donor DNA recombination efficiency (Abstract and Fig. 1), reading on claim 15. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use gene expression method of DiCarlo in view of Matsuyama to achieve respiratory stimulation to reduce lag phase in yeast as taught by van den Brink and van Dijken. The ordinary artisan would have been motivated to do so because DiCarlo teaches S. cerevisiae comprising constitutive Cas9 expression and transient expression of a gRNA cassette, and with near 100% donor DNA recombination efficiency and because Matsuyama expressly teaches manipulation of gene YLR108C. Therefore, modifications to van Dijken and van den Brink would be considered advantageous as provided by the teachings of DiCarlo and Matsuyama to reduce YLR108C expression. Accordingly, both the claimed invention and the prior art references, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time of filing. The ordinary artisan would have reasonable expectation of success in modifying the prior art reference to arrive at the claimed invention. Claim 5 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Chu ("The lag-phase during diauxic growth is a trade-off between fast adaptation and high growth rate."; published 2016) as applied to claim 5 above, and further in view of van den Brink (“New insights into the Saccharomyces cerevisiae fermentation switch: dynamic transcriptional response to anaerobicity and glucose-excess”, published 2008). Chu’s general disclosure relates to bi-phasic or diauxic growth is often observed when microbes are grown in chemically defined medium containing two sugars, wherein the growth stages are separated by a lengthy phase of arrested growth, lag-phase. Chu studies in environments where switching is less frequently required, lag-phase will evolve to be longer whereas, in frequently changing environments, the lag-phase will evolve to be shorter (see Abstract). Regarding claim 5, Chu discloses for both yeast and E. coli it was shown that the population is heterogeneous with respect to the activation state of the primary and secondary metabolism. During the lag-phase there are cells that grow on both the primary and the secondary nutrient. It appears that the lag-phase is the result of an unequal distribution of growth rates within the population rather than a reflection of the typical cell behavior (see page 2, second paragraph). Chu discloses that leak2 or leak, which is a constitutive expression of the permeases for the secondary metabolism, is an important determinant for the length of the lag-phase and linked to energy usage and increased metabolic burden on the cell (see page 5, paragraphs 3-9; Fig 3). It is noted that energy usage and metabolism are directed related to respiration; therefore, an ordinary artisan would recognize that leak2 or leak rates are linked to stimulation of respiration. Chu discloses the higher the leak rate the shorter the lag phase, wherein the leak expression requires cell-resources of at least two kinds: (i) Protein synthesis draws metabolic resources (i.e. ATP, ribosome sequestration, etc.); (ii) inserting permeases at the cell surface requires space which is then not available to other cell functions (see page 8, second paragraph). Therefore, Chu discloses stimulating respiration or metabolism of a secondary carbon source by enhancing leak expression (or an activator of respiration) in yeast cells to reduce the lag phase. Regarding claim 11, Chu discloses that a microbial population first grows exponentially on glucose until all glucose is exhausted, then stops growing for a considerable amount of time (lag-phase) and subsequently resumes exponential growth on lactose (see page 1, first paragraph). Therefore, Chu discloses that the lag phase is associated with the depletion of glucose in the growth medium. Regarding claim 5, Chu does not teach: reducing the expression of as YLR108C van den Brink’s general disclosure relates to the capacity of respiring cultures of yeast to immediately switch to fast alcoholic fermentation upon a transfer to anaerobic sugar-excess conditions (see Abstract). The goal of the van den Brink’s study was to investigate the dynamic adaptation of S. cerevisiae to the industrially relevant transition from aerobic, sugar-limited and respiratory growth to fully fermentative (i.e., anaerobic glucose-excess) conditions and to dissect responses to the glucose up-shift and onset of anaerobicity (see Background). Therefore, van den Brink’s general disclosure relates to the lag phase and the respiration of yeast by studying their response to glucose and oxygen depletion. van den Brink’s study observed the initial response to fully fermentative conditions showed quite some overlap with published datasets for glucose pulses to aerobic cultures, including induction of the translational machinery and repression of the respiratory chain and aimed to go beyond the primary response to see how yeast adjusted to its altered growth environment (see page 7, “Secondary response”, first paragraph). van den Brink teaches that under these conditions, regulatory factors involved in regulation of the respiratory chain (HAP2, HAP4 and HAP5) were down-regulated together with their targets (see page 8, col. 2, first paragraph). Further, in an attempt to identify robust 'signature transcripts' that show a consistent response to anaerobiosis, the set of significantly responding genes in this dynamic study was compared with several datasets from glucose pulses and aerobic-to-anaerobic shift experiments. van den Brink teaches that the majority of the anaerobic down-regulated genes had functions related to mitochondrial function or oxidative stress response, of which 13 genes contained a Hap1 or Hap2/3/4/5 binding element (see page 9, “Anaerobic “signature” transcripts”, first paragraph). True "signature" transcripts for anaerobicity both within dynamic and steady state conditions are listed in Table 3, which includes the gene YLR108C (see Table 3). van den Brink teaches that the observed reprogramming of the transcriptome was mostly driven by relief from the glucose-limitation, exemplified by preparation for faster growth (induction of ribosomes, nucleotide biosynthesis and amino acids biosynthesis) and glucose repression of various metabolic pathways (see page 11, col. 1, first paragraph). Therefore, regarding claim 5, in order to reduce fermentative responses and reprogramming of the transcriptome to respond to oxygen depletion, one of ordinary skill in the art would recognize that the van den Brink teaches signature transcripts or genes to investigate to stimulate respiration and reduce lag phase. van den Brink teaches up-regulated and down-regulated genes in response to anaerobic conditions, therefore directly providing a list of genes associated with fermentative conditions and alcohol production. Therefore, an ordinary artisan would be motivated to enhance expression of an activator of respiration and reduce the expression of a repressor of respiration in order to reduce the lag phase by stimulating respiration. Regarding claim 5, through routine experimentation and provided guidance from van den Brink, an ordinary artisan would investigate YLR108C as a repressor of respiration since it is taught as “signature” transcript by van den Brink in response to anaerobicity (see Table 3). An ordinary artisan would have reasonable expectation of success in selecting YLR108C and reducing its expression to result in stimulation of respiration in yeast cells. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify gene expression in yeast cells to enable respiration and reduce lag phase as taught by van den Brink and Chu. The ordinary artisan would have been motivated to do so because Chu teaches discloses stimulating respiration or metabolism of a secondary carbon source in yeast cells to reduce the lag phase, and van den Brink teaches signature transcriptional genes associated with switching from aerobic glucose-limited yeast to anerobic sugar-excess conditions. Therefore, an ordinary artisan with the teachings of van den Brink and Chu would select one of the signature transcriptional gene, i.e. YLR108C, associated with respiration as taught by van den Brink and reduce or enhance its expression to overcome or reduce the lag phase as taught by Chu. Accordingly, both the claimed invention and the prior art references, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time of filing. The ordinary artisan would have reasonable expectation of success in modifying the prior art reference to arrive at the claimed invention because van den Brink and Chu are directed to aerobic and fermentative kinetics of yeast cells. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Chu and van den Brink, as applied to claim 5 above, and further in view of Matsuyama (US Pub No. 2013/0244243 A1) and DiCarlo (Nucleic Acids Research (2013), 41(7), 4336-4343). The teachings of Chu and van Dijken are relied upon as set forth above. Regarding claim 15, Chu and van den Brink do not teach chimeric gene expression in yeast cells. Matsuyama’s general disclosure relates to a method for producing an expression product of an exogenous gene in a yeast with superior output regulation of gene expression. Regarding claim 15, Matsuyama teaches genome integration by homologous recombination and genetic recombination using shuttle vectors with E. coli is a method that is used to cause expression of arbitrary exogenous genes in Saccharomyces cerevisiae and other yeasts and the like, and teaches promoters, terminator regions and the like for causing expression of the introduced gene are also incorporated in advance (see para. [0003]). Matsuyama teaches that the yeast gene can be YLR108C (see para. [0011]). Therefore, Matsuyama teaches a method of expressing a chimeric gene construct comprising a promotor and the gene YLR108C, achieving respiratory stimulation. DiCarlo teaches S. cerevisiae comprising constitutive Cas9 expression and transient expression of a gRNA cassette, and with near 100% donor DNA recombination efficiency (Abstract and Fig. 1), reading on claim 15. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use gene expression method of DiCarlo in view of Matsuyama to achieve respiratory stimulation to reduce lag phase in yeast as taught by Chu and van den Brink. The ordinary artisan would have been motivated to do so because DiCarlo teaches S. cerevisiae comprising constitutive Cas9 expression and transient expression of a gRNA cassette, and with near 100% donor DNA recombination efficiency and because Matsuyama expressly teaches manipulation of gene YLR108C. Therefore, modifications to Chu and van den Brink would be considered advantageous as provided by the teachings of DiCarlo and Matsuyama to reduce YLR108C expression. Accordingly, both the claimed invention and the prior art references, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time of filing. The ordinary artisan would have reasonable expectation of success in modifying the prior art reference to arrive at the claimed invention. Response to Arguments Applicant's arguments on pages 4-8 of the reply have been fully considered, but not found persuasive of error for the reasons given below. On pages 4-5 of the reply, Applicant alleges that the instant claim amendments overcome the obviousness rejection of record over van Dijken in view of van den Brink. This is not found persuasive of error because the instant amendments to claim 5 have only removed the non-elected species of YDR132C, which does not impact the rejection of the elected species of YLR108C over van Dijken in view of van den Brink. On pages 5-6 of the reply, Applicant alleges that it would have been unpredictable to combine the teachings of van der Brink with van Dijken. This is not found persuasive because clearly teaches a known correlation between the downregulation of YLR108C and anaerobicity in yeast, and one of ordinary skill in the art would recognize that the van den Brink teaches signature transcripts or genes to investigate to stimulate respiration and therefore reduce lag phase. Absolute predictability is not a prerequisite for a prima facie case for obviousness, see M.P.E.P. § 2143.02 (I) and (II), and Applicant’s arguments of unpredictability appear to be predicated on the faulty premise that the rejection of record relies upon an “obvious to try rationale”. A specific motivation to combine the references is set forth above, and reproduced as follows: “Regarding claim 5, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify gene expression in yeast cells to enable respiration and reduce lag phase as taught by van den Brink and van Dijken. The ordinary artisan would have been motivated to do so because van Dijken teaches production of ethanol and acetate upon transfer from glucose depletion to glucose excess due to respiratory inabilities, and van den Brink teaches signature transcriptional genes associated with switching from aerobic glucose-limited yeast to anerobic sugar-excess conditions. Therefore, an ordinary artisan with the teachings of van den Brink and van Dijken would select one of the signature transcriptional gene, i.e. YLR108C, associated with respiration as taught by van den Brink and reduce or enhance its expression to overcome or reduce the lag phase and/or Crabtree effect in yeast cells as taught by van Dijken.” On page 6 of the reply, Applicant alleges that van den Brink is deficient by not teaching that HAP factor regulation is not correlated to YLR108C. Applicant’s argument appears to be suggesting that there is no teaching, suggestion, or motivation to combine the references. While the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Applicant’s arguments are not persuasive because they do not address the specific rationale to combine the references as set forth above and reproduced in the preceding paragraph. Note that the prior art does not need to set forth an explicit teaching of a motivation to combine, only that any rationale to combine prior art references in support of a prima facie case for obviousness under 35 U.S.C. § 103 be made explicit, see M.P.E.P. § 2143, the 4 paragraphs before subheading (I). On page 7 of the reply, Applicants rely on arguments traversing the above rejection of claims 5 and 11 over van Dijken in view of van den Brink to traverse the rejection of claim 15 further in view of Matsuyama and DiCarlo, and the rejection of claims 5 and 11 over Chu and view of van den Brink. Therefore, the response set forth above to arguments also applies to this rejection. Conclusion No claims are allowed. No claims are free of the art. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F). 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, Sharmila Landau can be reached at 571-272-0614. 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. /Sean C. Barron/Primary Examiner, Art Unit 1653
Read full office action

Prosecution Timeline

Jul 29, 2021
Application Filed
Nov 06, 2024
Non-Final Rejection — §103, §112, §DP
Feb 14, 2025
Response Filed
Jun 03, 2025
Final Rejection — §103, §112, §DP
Jul 24, 2025
Response after Non-Final Action
Aug 06, 2025
Request for Continued Examination
Aug 08, 2025
Response after Non-Final Action
Jan 26, 2026
Response Filed
Feb 23, 2026
Non-Final Rejection — §103, §112, §DP (current)

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Prosecution Projections

3-4
Expected OA Rounds
53%
Grant Probability
85%
With Interview (+31.6%)
3y 8m
Median Time to Grant
High
PTA Risk
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