DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
The amended claim set filed on 20 November 2025 is acknowledged. Claims 1-6, 8-17, and 19-24 are currently pending. Of those, claims 1, 8-12, and 19-24 are amended. There are no new claims and no claims are withdrawn. Claims 7 and 18 are cancelled. Claims 1-6, 8-17, and 19-24 will be examined on the merits herein.
Response to Amendment
The Applicants’ arguments filed 20 November 2025 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Non-Final Office Action mailed 20 May 2025 will be referred to “NFOA”.
Objection(s) and Rejection(s) Withdrawn
The objection to the drawings is withdrawn in view of the replacement drawings filed on 20 November 2025.
The objection to the specification is withdrawn in view of the substitute specification filed on 20 November 2025.
The objection(s) to and rejection(s) under 35 U.S.C. 112(b) and/or 112(a) of claims 7 and 18 are moot because those claims are cancelled.
The objections to claims 1 and 8-11 are withdrawn in view of the claim amendments.
The rejection of claims 1-6, 8-17, and 19-24 under 35 U.S.C. 112(b) is withdrawn in view of the claim amendments.
The rejections of claims 1-6, 8-17, and 19-24 under 35 U.S.C. 112(a) (enablement and written description) are both withdrawn in view of the claim amendments.
The rejection of claims 10, 12, and 19-22 under 35 U.S.C. 112(d) is withdrawn in view of the claim amendments.
The rejection of claims 1-6, 17, and 24 under 35 U.S.C. 102(a)(1) is withdrawn in view of the claim amendments.
Objection(s) Maintained
Claim 23 remains objected to because of the following informalities: the abbreviations “MVAP” and “IP” should be spelled out upon first use in the claims. Appropriate correction is required.
Response to Arguments
Applicant argues (Remarks, pg. 8) that claim 23 was amended to address formality issues, thereby addressing the objection raised in the NFOA.
This argument has been fully considered but is not persuasive. This argument is not persuasive because the claim amendments did not spell out the complete terms for “MVAP” and “IP” as was set forth in the objection.
New Rejection(s)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112(b)
Claims 1-6, 11-17, and 24 are newly 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.
Claim 1 (upon which claims 2-6, 11-16, and 24 depend) recites, “wherein the genetically modified yeast host cell is modified to overexpress HMG-CoA synthase (MvaS), acetoacetyl-CoA thiolase/HMG-CoA reductase (MvaE), mevalonate kinase (MK) (or ERG12), and phosphomevalonate decarboxylase (ERG19).” Claim 17 recites, “wherein the genetically modified yeast host cell is engineered to be reduced in expression for farnesyl pyrophosphate synthase (ERG20).” Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The terms “MvaS", "MvaE", "ERG12", and "ERG19” in claim 1 and “ERG20” in claim 17 are used by the claims to refer to the generic enzymes, while the accepted meaning is that “MvaS” and “MvaE” refer to the bacterial versions of the recited HMG-CoA synthase, acetoacetyl-CoA thiolase, and/or HMG-CoA reductase genes, respectively, and “ERG12”, “ERG19”, and “ERG20” refer to yeast mevalonate kinase, phospomevalonate decarboxylase genes, and farnesyl pyrophosphate synthase, respectively (as is evidenced by Liao et al., pg. 697, “Abbreviations” section). The term is indefinite because the specification does not clearly redefine the term, and it is unclear if the gene names in parentheses are examples of each recited gene (i.e., are optional) or are intended to limit the scope of the claim to bacterial or yeast versions of the recited genes. In the interest of compact prosecution, the broadest reasonable interpretation of claims 1 and 17 is that these claims recite generic HMG-CoA synthase, acetoacetyl-CoA thiolase and/or HMG-CoA reductase, mevalonate kinase (MK), phosphomevalonate decarboxylase, and farnesyl pyrophosphate synthase genes (i.e., any of the genes may be from bacteria or yeast).
Claim Rejections - 35 USC § 102
Claims 1-6, 21-22, and 24 are newly rejected under 35 U.S.C. 102(a)(1) as being anticipated by Westfall et al. (2012, Proc. Natl. Acad. Sci. USA; herein “Westfall”) as evidenced by Liao et al. (2016, Biotechnol. Adv.; herein “Liao”).
Regarding claims 1-6, Westfall teaches a Saccharomyces cerevisiae (S. cerevisiae) strain CEN.PK2 overexpressing every enzyme of the mevalonate pathway (Abstract). These enzymes include ERG10 (yeast acetyl-CoA thiolase, as evidenced by Liao, pg. 697, “Abbreviations” section), ERG13 (yeast HMG-CoA synthase, as evidenced by Liao), tHMG1 (HMG-CoA reductase; see pg. E113, left col., para. 1), ERG12, and ERG19 (Fig. 2A). S. cerevisiae possessed the native MVA pathway, meaning that it is inherently capable of producing isoprenol, as is evidenced by Liao (section 3.3, para. 1 and Fig. 1).
Regarding claims 21-22, Westfall teaches that ERG19 and ERG12 were amplified and cloned from S. cerevisiae genomic DNA (Supplemental, pg. 2, left col., para. 4, and pg. 2, right col., para. 1).
Regarding claim 24, Westfall teaches a method comprising growing the genetically modified S. cerevisiae (i.e., providing the genetically modified S. cerevisiae) in flask or fermenter media (pg. E116, right col., para. 3).
Claim Rejections - 35 USC § 103
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.
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 1-6, 8, 19-22, and 24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Westfall et al. (2012, Proc. Natl. Acad. Sci. USA; herein “Westfall”) as evidenced by Liao et al. (2016, Biotechnol. Adv.; herein “Liao”) in view of Korman et al. (2013, Protein Sci.; herein “Korman”) and Chou and Keasling (2012, Appl. Environ. Microbiol.; herein “Chou”).
The teachings of Westfall with respect to claims 1-6, 21-22, and 24 are set forth in the 102 rejection above.
Regarding claim 8, Westfall also teaches that S. cerevisiae CEN.PK2 overexpresses ERG8 (Fig. 2A).
However, Westfall does not teach a genetically modified yeast cell capable of producing isoprenol modified to EfmvaS, EfmvaE, and NudB as in claims 8 and 19-20.
Regarding claims 8 and 19-22, Korman teaches a method of producing isoprenoids in vitro using purified enzymes obtained by genetically modifying E. coli by overexpressing acetoacetyl-CoA thiolase/HIG-CoA reductase (MvaE) and HMG- CoA synthase (MvaS) from E. faecalis (i.e., EfmvaE and EfmvaS) and ERG12, ERG8 and mevalonate pyrophosphate decarboxylase, i.e., phosphomevalonate decarboxylase from S. cerevisiae (i.e., ERG12sc, ERG8sc, and ERG19sc) (Abstract and Table 1).
Regarding claim 8, Chou teaches that the overexpression of NudB, which is the enzyme that converts IPP to IP (i.e., the immediate precursor to isoprenol), in E. coli led to the highest production of isoprenol in vivo, when compares to other Nud enzymes, including B. subtilis NudF (pg. 7851, right col., para. 2 and Fig. 2B). Chou also teaches that isoprenol is a biofuel obtained from renewable resources with better combustion efficiency than ethanol, which is used as a gasoline substitute (pg. 7849, left col., para. 1 and right col., para. 2). Chou teaches that hmgS (i.e., HMG-CoA synthase), hmgR (i.e., HMG-CoA reductase), mk (i.e., mevalonate kinase), pmk (i.e., phosphomevalonate kinase), and pmd (i.e., phosphomevalonate decarboxylase) are genes encoding enzymes necessary to produce isoprenol (FIG 1).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the S. cerevisiae CEN.PK2 taught by Westfall by overexpressing the E. faecalis MvaE and MvaS genes taught by Korman and by overexpressing NudB, as is taught by Chou, thereby arriving at the invention of claims 1-6, 8, 19-22, and 24. The person of ordinary skill in the art would have been motivated to make the modification because Chou teaches that HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, and phosphomevalonate decarboxylase, which are overexpressed in S. cerevisiae by Westfall and used in vitro by Korman, are necessary enzymes to produce isoprenol, which is a renewable biofuel. Additionally, Chou demonstrates that overexpression of NudB results in increased isoprenol production. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully overexpressing all of EfmvaE, EfmvaS, ERG12sc, ERG19sc, ERG8sc, and NudB in S. cerevisiae because Westfall teaches the methodological details necessary to overexpress genes in S. cerevisiae, and Chou teaches that overexpression of each of those enzymes would predictably lead to an increase in the amount of isoprenol made by the MVA pathway in S. cerevisiae. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., EfmvaE, EfmvaS, ERG8sc, ERG12sc, ERG19sc, and NudB overexpression) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1-6, 8-9, 11, 19-22, and 24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Westfall as evidenced by Liao in view of Korman and Chou as applied to claims 1-6, 8, 19-22, and 24 above, and further in view of Chatzivasileiou et al. (2019, Proc. Natl. Acad. Sci. USA; herein “Chatzivasileiou”).
The combination of Westfall, Korman, and Chou is set forth in para. 26-59 above and teaches all elements of claims 1-6, 8, 19-22, and 24.
Westfall also teaches methods of overexpressing endogenous MVA genes in which MVA pathway genes were inserted into loci of other endogenous genes, thereby knocking out the gene(s) within the target loci (Supplemental pg. 2).
However, none of Westfall, Korman, or Chou teach a genetically modified yeast host cell engineered to be knocked out for an endogenous PMK, a cytosolic enzyme that acts in the biosynthesis of isoprenoids and sterols, and/or an endogenous choline kinase, as in claims 9 and 11.
Regarding claims 9 and 11, Chatzivasileiou teaches that isoprenol is converted to IP by kinases, including choline kinase in S. cerevisiae (Fig 1A-C). Chatzivasileiou also teaches that S. cerevisiae choline kinase produced more IP and IPP from isoprenol in vitro than any of the other kinases they tested (Fig 1C).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the S. cerevisiae produced by the combination of Westfall, Korman, and Chou by knocking out the endogenous choline kinase, thereby arriving at the invention of claims 1-6, 8-9, 11, 19-22, and 24. The person of ordinary skill in the art would have been motivated to make the modification because Chatzivasileiou teaches that choline kinase converts isoprenol into IP, which is then converted to IPP; thus, in an S. cerevisiae genetically modified to produce isoprenol for use as a biofuel, it would be beneficial to prevent isoprenol from being consumed by choline kinase. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully producing a yeast host cell capable of producing isoprenol because the S. cerevisiae produced using the teachings of Westfall, Korman, and Chou is naturally capable of producing isoprenol and one would predict that knocking out endogenous choline kinase would not render the S. cerevisiae cell incapable of producing isoprenol, based on the teachings of Chatzivasileiou. One of ordinary skill in the art would have had a reasonable expectation of successfully knocking out the choline kinase gene in S. cerevisiae because Westfall teaches genetic modifications in which endogenous genes are knocked out.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that a modification is obvious when some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. The courts have made clear that the teaching, suggestion, or motivation test is flexible and an explicit suggestion to combine the prior art is not necessary. The motivation to combine may be implicit and may be found in the knowledge of one of ordinary skill in the art, or, in some cases, from the nature of the problem to be solved. DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., at 1366, 80 USPQ2d at 1649. "[A]n implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the ‘improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal—and even common-sensical—we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves. In such situations, the proper question is whether the ordinary artisan possesses knowledge and skills rendering him capable of combining the prior art references." Id. at 1368, 80 USPQ2d at 1651. In this case, the art provides the motivating teaching to improve isoprenol production, and there is a reasonable expectation of success, as discussed above, due to the known genetic engineering techniques and the lack of a claimed functional outcome. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Claims 1-6, 8, 10, 12, 19-22, and 24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Westfall as evidenced by Liao in view of Korman and Chou as applied to claims 1-6, 8, 19-22, and 24 above, and further in view of Kang et al. (2016, Metab. Eng.; herein “Kang”).
The combination of Westfall, Korman, and Chou is set forth in para. 26-59 above and teaches all elements of claims 1-6, 8, 19-22, and 24.
However, none of Westfall, Korman, or Chou teach a genetically modified yeast host cell engineered to have increased expression of a phosphatase, as in claims 10 and 12.
Regarding claims 10 and 12, Kang teaches that the IPP-bypass mevalonate pathway is a pathway for the biological production of isoprenol that is beneficial for in vivo isoprenol production because of the lower ATP cost and avoidance of toxic IPP that is produced in the MVA pathway (pg. 28, left col., para. 2). Kang teaches that this pathway is achieved in E. coli by implementing PMD (i.e., ERG19) from S. cerevisiae and the E. coli-endogenous phosphatase AphA, which have promiscuous activity for MVAP (Abstract). Kang also teaches that, in the MVA pathway, phosphomevalonate kinase (PMK) converts MVAP to MVAPP, which is then transformed into IPP (section 3.1, para. 1 and Fig. 1).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the S. cerevisiae produced by the combination of Westfall, Korman, and Chou by overexpressing the AphA phosphatase, thereby arriving at the invention of claims 1-6, 8, 10, 12, 19-22, and 24. The person of ordinary skill in the art would have been motivated to make the modification because Kang teaches that AphA allows for the production of isoprenol through the IPP-bypass mevalonate pathway, thereby adding to the isoprenol production of the MVA pathway. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully expressing AphA in S. cerevisiae because Westfall teaches the methodological details needed to overexpress genes in S. cerevisiae, and Kang teaches that AphA can be combined with S. cerevisiae ERG19 in order to produce isoprenol. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., EfmvaE, EfmvaS, ERG8sc, ERG12sc, ERG19sc, and NudB overexpression and AphA overexpression) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1-6, 15-16, 21-22, and 24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Westfall as evidenced by Liao in view of Baek et al. (2016, Appl. Microbiol. Biotechnol.; herein “Baek”).
The teachings of Westfall with respect to claims 1-6, 21-22, and 24 are set forth in the 102 rejection above.
Westfall also teaches that acetyl-CoA (which is produced from pyruvate) is a substrate required in the MVA pathway, which is used to produce amorphadiene (Fig. 2A).
However, Westfall does not teach a genetically modified yeast host cell engineered to be knocked out for an endogenous GDP1 and/or one or more ADH genes, as in claims 15-16.
Regarding claims 15-16, Baek teaches that GPD1 converts DHAP produced from glucose into G3P, and PDC and ADH genes convert pyruvate to ethanol (Fig. 1a and pg. 2737, right col., para. 2 – pg. 2738). Baek teaches that S. cerevisiae CEN.PK2-1C (i.e., a modified S. cerevisiae CEN.PK2) containing deletions of ADH1, GPD1, and GPD2 led to a decrease in ethanol production and elimination of glycerol accumulation (pg. 2743, left col., para. 1), thereby increasing the amount of lactic acid produced from pyruvate (pg. 2743, right col., para. 1). Baek also teaches that deletions in ADH2, ADH3, ADH4, and ADH5 have been known to increase lactic acid production from pyruvate (pg. 2738, left col.). Fig. 1a teaches that deletion of GPD genes and ADH genes eliminates alternative pathways that utilize DHAP and pyruvate, allowing for the accumulation of pyruvate, which Baek used to produce lactic acid.
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the S. cerevisiae CEN.PK2 taught by Westfall by knocking out GPD1 and GPD2 as well as ADH1, ADH2, ADH3, ADH4, and ADH5, as is taught by Baek, thereby arriving at the invention of claims 1-6, 15-16, 21-22, and 24. The person of ordinary skill in the art would have been motivated to make the modification because Baek teaches that deletion of the GPD and ADH genes eliminates pathways that utilize DHAP (a precursor to pyruvate) and pyruvate, which is a precursor to acetyl-CoA, which Westfall teaches is necessary to produce amorphadiene. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully modifying the S. cerevisiae produced by Westfall because Baek teaches the methodological details necessary to successfully delete GPD and ADH genes from CEN.PK2-1C (a derivative of the strain made by Westfall). One of ordinary skill in the art would have had a reasonable expectation of successfully producing an S. cerevisiae capable of producing isoprenol because one would predict that knocking out GPD and ADH genes would not prevent S. cerevisiae from producing isoprenol using its natural MVA pathway. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., HMG-CoA synthase, acetoacetyl-CoA thiolase, HMG-CoA reductase, mevalonate kinase, and phosphomevalonate decarboxylase overexpression and GPD and ADH deletions) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1-6, 15-16, and 21-24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Westfall as evidenced by Liao in view of Baek as applied to claims 1-6, 15-16, 21-22, and 24 above, and further in view of Ma et al. (2011, Metab. Eng.; herein “Ma”).
The combination of Westfall and Baek is set forth in para. 46-59 above and teaches all elements of claims 1-6, 15-16, 21-22, and 24.
The teachings of Baek with respect to claims 15-16 also apply to claim 23.
However, neither Westfall nor Baek teach a genetically modified yeast host cell engineered to overexpress an NADH-dependent HMG-CoA reductase, as in claim 23.
Regarding claim 23, Ma teaches a genetically modified E. coli strain engineered to express the MVA pathway enzymes from S. cerevisiae used to produce amorphadiene (Abstract and section 2.2). Ma teaches that this strain was further engineered to express various HMGR (HMG-CoA reductase) from various organisms, and that expression of NADH-dependent HMGR from Delftia acidovorans resulted in the best production of amorphadiene compared to other HMGR genes (section 2.3 and Abstract).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the S. cerevisiae produced by the combination of Westfall and Baek by overexpressing the NADH-dependent HMG-CoA reductase from D. acidovorans, thereby arriving at the invention of claims 1-6, 15-16, and 21-24. The person of ordinary skill in the art would have been motivated to make the modification in order to further increase the production of amorphadiene because Ma teaches that expression of NADH-dependent HMG-CoA reductase from D. acidovorans resulted in increased production of amorphadiene in E. coli. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully expressing NADH-dependent HMG-CoA reductase from D. acidovorans in S. cerevisiae because Westfall and Baek teach the methodological details necessary to overexpress genes in S. cerevisiae and Ma teaches that NADH-dependent HMG-CoA reductase from D. acidovorans is able to increase production of amorphadiene when combined with S. cerevisiae MVA pathway genes. One of ordinary skill in the art would have a reasonable expectation of successfully producing a S. cerevisiae capable of producing isoprenol through its native MVA pathway because one would predict that overexpression of NADH-dependent HMG-CoA reductase from D. acidovorans would not prevent the native MVA pathway from functioning, based on the teachings of Ma. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., HMG-CoA synthase, acetoacetyl-CoA thiolase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate decarboxylase, and NADH-dependent HMG-CoA reductase overexpression and GPD and ADH deletions) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 1-6, 8, 17, 19-22, and 24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Westfall as evidenced by Liao in view of Korman and Chou as applied to claims 1-6, 8, 19-22, and 24 above, and further in view of Pham (2015; cited in IDS).
The combination of Westfall, Korman, and Chou is set forth in para. 26-59 above and teaches all elements of claims 1-6, 8, 19-22, and 24.
However, none of Westfall, Korman, or Chou teach a genetically modified yeast host cell engineered to be reduced in expression for farnesyl pyrophosphate synthase, as in claim 17.
Regarding claim 17, Pham teaches S. cerevisiae W303 having reduced expression of ERG20 generates higher amounts of isoprenol and prenol than strains in which ERG20 expression is not repressed (pg. 96).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the S. cerevisiae strain produced by the combination of Westfall, Korman, and Chou to have reduced expression of ERG20, thereby arriving at the invention of claims 1-6, 8, 17, 19-22, and 24. The person of ordinary skill in the art would have been motivated to make the modification because Pham teaches that repression of ERG20 results in increased isoprenol production, which Chou teaches is a renewable biofuel. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Pham teaches the methodological details necessary to successfully repress ERG20 expression. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., EfmvaE, EfmvaS, ERG8sc, ERG12sc, ERG19sc, and NudB overexpression and ERG20 repression) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Allowable Subject Matter
Claims 13-14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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, DANIEL KOLKER can be reached at (571) 272-3181. 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.
/BAILEY M MORGAN/Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645