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 .
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the current case, the view numbers for Figures 1-15 are preceded by the word "Figure" instead of the abbreviation "FIG.".
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(d)
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 14 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.
Regarding Claim 14, Claim 14 recites “wherein the genes are integrated into the S. cerevisiae genome in any order”. Claim 1 and 6 comprise of a step for integrating genes into the S. cerevisiae genome. Claim 1 and Claim 6 do not specify an order for the integration of genes, which allows for the integration of genes in any order. Therefore, Claim 14 does not further limit Claim 6.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 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 1, 3-6, 9, 14, 15, 23, and 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Sanda, T., et. al., Bioresource Technology, Vol. 102, No. 17, p.7917-7924, published September 2011; and Hasunuma, T. and Kondo, A., Biotechnology Advances, Vol. 30, No. 6, p. 1207-1218, published November 2012.
Regarding Claim 1, Sanda teaches a method of producing a modified S. cerevisiae yeast strain with enhanced resistance to weak acids, the method comprising integrating at least one copy of a TAL1 gene and at least one copy of a FDH1 gene into a S. cerevisiae yeast genome, so that the modified yeast strain overexpresses these genes relative to a S. cerevisiae yeast strain that has not been modified in the same manner: “a recombinant xylose-fermenting S. cerevisiae strain that demonstrated higher ethanol production in the presence of both acetate and formate was constructed by expressing both transaldolase (TAL) and formate dehydrogenase (FDH) genes from S. cerevisiae” (p. 7918, col. 2). Sanda teaches other enzymes have been explored for “detoxification of inhibitors, such as furan derivatives and phenolic compounds” (p. 7917, col. 2). Sanda provides motivation for further identification and integration of additional enzymes into the S. cerevisiae genome for more greater efficiency: “Identification of additional enzymes involved in the transformation of inhibitors and subsequent metabolic engineering approaches appears to be a very promising strategy for obtaining even more efficient strains”.
Sanda does not teach a method of producing a modified S. cerevisiae yeast strain with enhanced resistance to furans and phenolics, and the use of the ADH6 gene and ARI1 gene.
Hasunuma teaches that multiple genetic engineering solutions to furan and phenolics have been explored in S. cerevisiae: “Overexpression of homologous or heterologous genes encoding these enzymes has been successfully applied to the detoxification of inhibitors such as furan derivatives and phenolic compounds”. Hasunuma teaches ADH6 overexpression and ARI1 overexpression as successful strategies for enhanced resistance to furans and phenolics (p. 1214, col. 1-2; p. 1215, Table 2). Hasunuma also provides a suggesting for exploring further modifications: “Tolerant yeast strains can be obtained by enhancing the genetic background” (p. 1216).
Regarding Claim 1, it would have been obvious to one skilled in the art before the effective filing date to have modified the method taught by Sanda to create a S. cerevisiae strain with an overexpressed TAL1 and FDH1 gene with additional overexpressed ADH6 or ARI1 genes taught by Hasunuma. Sanda teaches a S. cerevisiae strain with an overexpressed TAL1 and FDH1 gene for weak acid resistance, teaches other gene modifications could provide furan and phenolics resistance, and provides a suggestion that further modifications could produce more efficient strains. Hasunuma teaches modifying S. cerevisiae strains to overexpress ADH6 and ARI1 provides furan and phenolics resistance, and provides a suggestion for more tolerant yeast by enhancing the genetic background. The combined method would have a reasonable expectation of success as each gene has been interrogated and successfully created more efficient S. cerevisiae strains. Therefore, Claim 1 is obvious over Sanda and Hasunuma.
Regarding Claim 3, Sanda does not teach partial or complete deletion of FPS1.
Hasunuma teaches FPS1 disruption leads to “increased growth and ethanol production from glucose in the presence of acetic acid” (p. 1215, Table 2).
It would have been obvious to one skilled in the art to further modify the method of Claim 1 with teachings of Hasunuma to partially or completely delete the FPS1 gene because both Sanda and Hasunuma provide a suggestion for gene modification for resistance to weak acids and Hasunuma provides a reasonable expectation of success as deleting FPS1 successfully created more efficient S. cerevisiae strains. Therefore, Claim 3 is obvious over Sanda and Hasunuma.
Regarding Claim 4, Sanda teaches in their method the use of the PGK1 promoter, which is a constitutive promoter (p. 7918, Construction of plasmids). Therefore, Claim 4 is obvious over Sanda and Hasunuma.
Regarding Claim 5, Sanda teaches a xylose utilizing S. cerevisiae strain: “In order to increase ethanol production in the presence of both acetate and formate, the endogenous TAL1 gene coding TAL and the FDH1 gene coding FDH were expressed in a recombinant xylose-fermenting S. cerevisiae” (p. 7919, col. 2). Therefore, Claim 5 is obvious over Sanda and Hasunuma.
Regarding Claim 6, Claim 1 is obvious over Sanda and Hasunuma including where TAL1, FDH1, and ARI1 or TAL1, FDH1, and ADH6 are integrated into the genome of S. cerevisiae. Therefore, Claim 6 is obvious over Sanda and Hasunuma.
Regarding Claim 9, Claim 1 is obvious over Sanda and Hasunuma including where TAL1, FDH1, ARI1, and ADH6 are integrated into the genome of S. cerevisiae. Therefore, Claim 9 is obvious over Sanda and Hasunuma.
Regarding Claim 14, Claim 14 fails to further limit Claim 6 and is rejected under USC 35 112(d). Therefore, Claim 14 has the same limitations as Claim 6, and Claim 14 is obvious over Sanda and Hasunuma.
Regarding Claim 15, Claim 6 is obvious over Sanda and Hasunuma. Claim 15 recites an order in which the genes are integrated in a certain order. MPEP 2144.04.VI.C recites, “In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950) (Claims to a hydraulic power press which read on the prior art except with regard to the position of the starting switch were held unpatentable because shifting the position of the starting switch would not have modified the operation of the device.)”. It would have been obvious to one skilled in the art before the effective filing date that the order of genes integrated into S. cerevisiae would not have modified the operation of the modified S. cerevisiae. Therefore, Claim 15 is obvious over Sanda and Hasunuma.
Regarding Claim 23, Sanda and Hasunuma teach a method of creating a S. cerevisiae modified to overexpress at least a TAL1 gene and two or more of FDH1, ADH6, and ARI1 genes relative to an unmodified strain, wherein the modified strain has increased resistances to furans, phenolics and weak acids as described in Claim 1. Therefore, Claim 23 is obvious over Sanda and Hasunuma.
Regarding Claim 25, Sanda and Hasunuma teach Claim 23. Hasunuma further teaches the FPS1 gene partially or completely deleted as described in Claim 3 (p. 1215, Table 2). Therefore, Claim 25 is obvious over Sanda and Hasunuma.
Regarding Claim 26, Sanda and Hasunuma teach Claim 23. MPEP 2144.04.VI.B recites, “[T]he court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced”. One skilled in the art before the effective filing date would recognize that multiple copies of the gene integrated into S. cerevisiae would not produces new or unexpected results, and the instant specification does not provide support for new or unexpected results. Therefore, Claim 26 is obvious over Sanda and Hasunuma
Regarding Claim 27, Sanda and Hasunuma teach Claim 23. Sanda teaches in their method the use of the PGK1 promoter, which is a constitutive promoter (p. 7918, Construction of plasmid). Therefore, Claim 27 is obvious over Sanda and Hasunuma.
Regarding Claim 28, Sanda and Hasunuma teach Claim 23. Sanda teaches a xylose utilizing S. cerevisiae strain: “In order to increase ethanol production in the presence of both acetate and formate, the endogenous TAL1 gene coding TAL and the FDH1 gene coding FDH were expressed in a recombinant xylose-fermenting S. cerevisiae” (p. 7919, col. 2). Therefore, Claim 28 is obvious over Sanda and Hasunuma.
Claims 2, 10, 24, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Sanda, T., et. al., Bioresource Technology, Vol. 102, No. 17, p.7917-7924, published September 2011; and Hasunuma, T. and Kondo, A., Biotechnology Advances, Vol. 30, No. 6, p. 1207-1218, published November 2012 as applied to Claims 1 and 23 above, and further in view of Ghosh, A., et. al., The Journal of Biological Chemistry, Vol. 283, No. 15, p. 9768-6442, published April 11, 2008.
Regarding Claim 2, Sanda and Hasunuma teach Claim 1.
Sanda does not teach the PAD1 or ICT1 gene.
Hasunuma teaches PAD1 overexpression in S. cerevisiae for “[i]ncreased growth and ethanol production from glucose in the presence of ferulic and cinnamic acid under oxygen-limited conditions” (p. 1215, Table 2).
Ghosh teaches modifying S. cerevisiae by introduction and overexpression of ICT1 in S. cerevisiae for improving organic solvent tolerance: “To ascertain that the overexpression of ICT1 could rescue the growth delay of the organism on isooctane treatment … The strain overexpressing ICT1 was found to have an improved doubling time as compared with the vector control” (p. 9771, col. 1).
Regarding Claim 2, it would have been obvious to one skilled in the art to combine the teachings of Sanda and Hasunuma to create the method of Claim 1 and to further integrate at least one copy of the either or both of a PAD1 gene and ICT1 gene because Hasunuma and Ghosh teach their modifications provide further resistance to toxic compounds. The results would have been predictable because Sanda, Hasunuma, and Ghosh teach positive results of their methods and Hasunama teaches, “The yeast S. cerevisiae is also attractive because of its ease of genetic manipulation and is generally regarded as safe status due to its long association with the food and beverage industries”. Therefore, Claim 2 is obvious over Sanda and Hasunuma in further view of Ghosh.
Regarding Claim 10, Sanda and Hasunuma teach Claim 1 including the TAL1, FDH1, ARI1, ADH6, and PAD1 genes. Ghosh teaches the ICT1 gene. It would have been obvious to one skilled in the art before the effective filing date to combine the teachings of Sanda, Hasunuma, and Ghosh to create the method of Claim 1 with integration of the TAL1 and FDH1 genes, either one or both of the ARI1 and ADH6 genes, and either one or both of the PAD1 and ICT1 genes because Sanda, Hasunuma, and Ghosh teach their methods increase tolerance of S. cerevisiae to furans, phenolics, and weak acids. The results would have been predictable because Sanda, Hasunuma, and Ghosh teach positive results of their methods and Hasunama teaches S. cerevisiae is easy and safe to manipulate. Therefore, Claim 10 is obvious over Sanda and Hasunuma in further view of Ghosh.
Regarding Claim 24, Sanda, Hasunuma and Ghosh teach a method of creating the S. cerevisiae of Claim 23 which further overexpresses one or both of the PAD1 and ICT1 genes as described above in Claim 2. Therefore, Claim 24 is obvious over Sanda and Hasunuma in further view of Ghosh.
Regarding Claim 29, Sanda, Hasunuma and Ghosh teach a method of creating the S. cerevisiae of Claim 23 including with integrated copies of TAL1, FDH1, ARI1, ADH6, PAD1, and ICT1 into the S. cerevisiae as described above in Claim 2. Therefore, Claim 29 is obvious over Sanda and Hasunuma.
Claims 16, 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over de Villiers, T., “Fungal Enzymes and Microbial Systems for Industrial Processing”, Dissertation, Stellenbosch University, p. 1-154, dated March 2008; Hasunuma, T. and Kondo, A., Biotechnology Advances, Vol. 30, No. 6, p. 1207-1218, published November 2012; and Ghosh, A., et. al., The Journal of Biological Chemistry, Vol. 283, No. 15, p. 9768-6442, published April 11, 2008.
Regarding Claim 16, de Villiers teaches a double gene cassette where in the genes are under the control of a PGK1 or ENO1 promoter in use with S. cerevisae : “[S]train secreting the A. awamori glucoamylase and B. subtilis α-amylase as separate polypeptides from a double expression cassette performed the best” (p. 39); “[G]lucoamylase and α-amylase genes were inserted in frame with the XYNSEC secretion signal for constitutive expression under the transcriptional control of the S. cerevisiae PGK1 and ENO1 promoters and terminators respectively” (p. 69).
De Villiers does not teach the TAL1, FDH1, ARI1¸ ADH6, PAD1 or ICT1 genes.
Hasunuma teaches modifying S. cerevisiae by introduction and overexpression of the TAL1, FDH1, ARI1, ADH6, and PAD1 genes (p. 1215, Table 2).
Ghosh teaches modifying S. cerevisiae by introduction and overexpression of ICT1 in S. cerevisiae for improving organic solvent tolerance: “To ascertain that the overexpression of ICT1 could rescue the growth delay of the organism on isooctane treatment … The strain overexpressing ICT1 was found to have an improved doubling time as compared with the vector control” (p. 9771, col. 1).
Regarding Claim 16, it would been obvious to one skilled in the art before the effective filing date to substitute into the double gene expression cassette of de Villiers with the genes taught by Hasunuma, and Ghosh to create a double gene expression cassette comprising two of TAL1, FDH1, ARI1¸ ADH6, PAD1 or ICT1 because de Villiers teaches a double gene expression cassette for expression in S. cerevisiae and Hasunuma and Ghosh provide genes to modifying S. cerevisiae for improving tolerance to toxic compounds. The results would have been predictable because de Villiers provides evidence that they could create and express a double gene expression cassette in S. cerevisiae, and Hasunuma and Ghosh teach genes to substitute into the cassette for S. cerevisiae modification. One skilled in the art would have been motivated to do so because de Villiers teaches Hasunuma teaches multiple modifications improve tolerance in S. cerevisiae to toxic compounds. Therefore, Claim 16 is obvious over de Villiers, Hasunuma, and Ghosh.
Regarding Claim 21, de Villiers teaches the PGK1 promoter in their double gene expression cassette. Therefore, Claim 21 is obvious over de Villiers, Hasunuma, and Ghosh.
Regarding Claim 22, de Villiers teaches the ENO1 promoter in their double gene expression cassette. Therefore, Claim 22 is obvious over de Villiers, Hasunuma, and Ghosh.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Krishna Nuggehalli Ravindra whose telephone number is (571)272-2758. The examiner can normally be reached M-Th, alternate F, 8a-5p est.
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/K.N.R./ Examiner, Art Unit 1636
/NEIL P HAMMELL/ Supervisory Patent Examiner, Art Unit 1636