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 .
Withdrawal of Rejections
The response and amendments filed on 10/14/2025 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous 35 U.S.C. 112(b) rejection have been withdrawn necessitated by Applicant’s amendments.
The following rejection and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instantly invention.
Priority
The instant application filed on 12/07/2022 is a DIV of U.S. Application 16/612,918 filed on 11/12/2019 which is a 371 of PCT/KR2018/005425 filed on 05/11/2018 and claims priority to KR10-2018-0054080 filed on 05/11/2018 and KR10-2017-0058829 filed on 05/11/2017. The certified copies of foreign priority for KR10-2018-0054080 and KR10-2017-0058829 filed in the parent application 16/612,918 are not in English; therefore, the effective filing date of the claimed invention is 05/11/2018.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
No Information Disclosure Statement (IDS) has been filed in this application. Applicant
is reminded that each individual associated with the filing and prosecution of a patent application
has a duty of candor and good faith in dealing with the U.S. Patent and Trademark Office, which
includes a duty to disclose to the Office all information known to that individual to be material to
patentability (see 37 C.F.R. §1.56).
Maintained Objections
Drawing Objections
The drawings are objected to because:
Figures are ordered asynchronously as Figures 1, 2, 5, and 7. It is recommended that Figures 5 and 7 be renamed as Figures 3 and 4, respectively.
Higher quality images are required for Figures 1, 2, 5, and 7.
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.
New Grounds of Rejection Necessitated By Amendments
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-11 and 13-20 are rejected under 35 U.S.C. 103 as being unpatentable over Won (KR 2006/0040494; Date of Publication: May 10, 2006 – cited in the IDS filed in the parent application on 11/12/2019 – previously cited) and Renninger (US 2008/0274523; Date of Publication: November 6, 2008 – cited in the parent application on 09/20/2021 – previously cited).
Won’s general disclosure relates host cells expressing a mevalonic acid pathway (MVA) or non-mevalonic acid pathway (methylerythritol 4-phostphate pathway; MEP), wherein one or more genes of the MEP pathway are inactivated (see, e.g., Won, English translation, abstract). Additionally, Won teaches substances the inhibit either the MVA or MEP pathway, or both pathways (see, e.g., Won, English translation, abstract).
Regarding claims 1, 13-15, and 20 pertaining to a non-human organism, Won teaches Escherichia coli as the host cell (see, e.g., Won, English translation, “Description”, pg. 3, [5]).
Regarding claims 1 and 15 pertaining to the plasmids, Won teaches that DNA can be introduced into the host cell using a carrier, such as a plasmid (see, e.g., Won, English translation, “Description”, pg. 3, [8]).
Regarding claim 1 pertaining to gene(s) in the isopentenyl diphosphate or dimethylallyl diphosphate synthetic pathway being attenuated or deleted, Won teaches that genes encoding enzymes within the MEP pathway are inactivated within a host cell (see, e.g., Won, English translation, “Description”, pg. 3, [7]).
Regarding claims 1 and 15 pertaining to the selection marker gene, Won teaches the introduction of genes encoding enzymes within the MVA pathway (i.e., complementary genes) (see, e.g., Won, English translation, “Description”, pg. 3, [7]). Additionally, Won teaches transforming the host cell with DNA encoding all enzymes related to a foreign mevalonic acid pathway (see, e.g., Won, English Translation, pg. 2, “Description”).
Regarding claims 2 and 16 pertaining to the isopentenyl diphosphate or dimethylallyl diphosphate synthetic pathway, Won teaches that the MEP pathway is intrinsic to a host cell (see, e.g., Won, English translation, abstract).
Regarding claim 3 pertaining to the isopentenyl diphosphate or dimethylallyl diphosphate synthetic pathway, Won teaches host cells expressing a mevalonic acid pathway (MVA) or non-mevalonic acid pathway (methylerythritol 4-phostphate pathway; MEP) (see, e.g., Won, English translation, abstract).
Regarding claims 4-7 and 17 pertaining to the genes encoding enzymes in the isopentenyl diphosphate or dimethylallyl diphosphate synthetic pathway, Won teaches the inactivation of DXP reductoisomerase, which is a gene encoded in the MEP pathway within the host cell (see, e.g., Won, English translation, “Description”, pg. 3, [6]).
Regarding claims 7-8 and 18 pertaining to the complementary gene in the MVA pathway, Won teaches that DNA encoding enzymes involved in the MVA pathway were introduced into the host cell, such as HMG-CoA synthase, HMG-CoA reductase, and mevalonate kinase, (see, e.g., Won, English translation, “Description”, pg. 3, [7]).
Regarding claim 9 pertaining to the genes encoding enzymes in the isopentenyl diphosphate or dimethylallyl diphosphate synthetic pathway, Won teaches inhibitors of the MVA pathway (see, e.g., Won, English translation, Example 5, pg. 5). Moreover, Won teaches “The intrinsic non-mevalonic acid pathway is inactivated and inhibits either or both of the mevalonic acid pathway and the non-mevalonic acid pathway using a host cell transformed with DNA that encodes all enzymes involved in the foreign mevalonic acid pathway” (see, e.g., Won, English translation, “Description”, pg. 2, [1]).
However, Won does not teach: a target product gene, wherein the target product gene comprises a gene encoding a target protein other than the enzymes in the isopentenyl diphosphate or the dimethylallyl diphosphate synthetic pathway (claim 1); or wherein the target product comprises an enzyme in a pathway selected from the group consisting of isoprenoid, santalene, bisabolol and retinol synthetic pathways (claim 10); or wherein the target protein is an enzyme in a target product synthetic pathway synthesizing the target product (claim 11); or wherein the target product comprises the enzyme in a pathway selected form the group consisting of isoprenoid, santalene, bisabolol and retinol synthetic pathways.
Renninger’s general disclosure relates to “compositions and methods for a robust production of isoprenoids by the use of isopentenyl pyrophosphate pathway enzymes that are under the control of at least one heterologous regulator or fermentation conditions” (see, e.g., Renninger, [0007]).
Regarding claims 1, 10-11, and 19 pertaining to the target product gene, Renninger teaches genetically modified host cells for producing isoprenoids (see, e.g., Renninger, abstract). Moreover, Renninger teaches that the host cells comprise enzymes of the MVA or MEP pathways (see, e.g., Renninger, [0066]-[0083]), as well as genes encoding enzymes which produce isoprenoids from isopentenyl diphosphate or dimethylallyl diphosphate (see, e.g., Renninger, [0084]-[0162]). Furthermore, Renninger teaches that nucleic acids can be introduced into the host cells by a single or multiple vectors (see, e.g., Renninger, [0164]) and selectable markers which do not rely on the use of antibiotics can be used to identify host cells which are successfully transformed (see, e.g., Renninger, [0047], [0172], [0184]-[0187], Examples 17-18).
It would have been obvious to one of ordinary skill in the art before the effective filing date to produce a host cell, as taught by Won, wherein the host cell includes genes encoding enzymes of an isoprenoid pathway, as taught by Renninger, One would have been motivated to do so because Renninger teaches that that genes encoding enzymes within the isoprenoid pathway can be introduced into more than two plasmids and selectable markers that do not require the use of antibiotics can be employed (see, e.g., Renninger, [0047], [0164], [0172], [0184]-[0187], Examples 17-18). Moreover, production of isoprenoids by host cells would allow for an efficient and convenient manner of monitoring the effect of test substances on the host cells with MVA or MEP pathways, as described by Won. Therefore, based on the teachings of Won and Renninger, it would have been obvious to produce a host cell that expresses genes encoding enzymes within the isoprenoid pathway. One would have expected success because Won and Renninger both teach expression of the MVA and MEP pathways within host cells.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Won and Renninger as applied to claims 1-11 and 13-20 above, and further in view of Boronat (US 2002/0069426; Date of Publication: June 6, 2002 – previously cited).
The teachings of Won and Renninger, herein referred to as modified-Won-Renninger, are discussed above as it pertains to host cells expressing a mevalonic acid pathway (MVA) or non-mevalonic acid pathway (methylerythritol 4-phostphate pathway; MEP), wherein one or more genes of the MEP pathway are inactivated.
However, modified-Won-Renninger does not teach: wherein the target protein is green fluorescent protein (GFP) (claim 12).
Boronat’s general disclosure relates to the expression of novel genes within the MEP pathway (see, e.g., Boronat, abstract, [0003]).
Regarding claim 12 pertaining to the target protein, Boronat teaches the expression of GFP as a selectable marker within a vector (see, e.g., Boronat, [0180]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a host cell, as taught by modified-Won-Renninger, wherein the host cell expresses a gene encoding a GFP target protein, as taught by Boronat. One would have been motivated to do so because Boronat teaches that GFP can be used as an antibiotic-free selectable marker to select for cells that contain exogenous genetic material (see, e.g., Boronat, [0180]). Therefore, based on the teachings of Boronat and modified-Won-Renninger, it would have been obvious to produce a host cell that expresses GFP. One would have expected success because Boronat and modified-Won-Renninger both teach expression of the MEP pathway within cells.
Examiner’s Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Regarding Applicant’s argument pertaining to the rejection failing to identify the two required limitations (remarks, page 11), this argument is not persuasive for multiple reasons. First, Applicant argues that claim 1 requires co-localization; however, Renninger and Won both teach that the genes can be inserted into plasmids to be expressed into host cells (see, e.g., Won, English translation, “Description”, pg. 3, [8]) (see, e.g., Renninger, [0164]); therefore, the skilled artisan would readily understand that the selection marker gene and the target gene, as taught by Won and Renninger, can be inserted into the same plasmid. Secondly, Applicant states that the selection marker gene is “comprising at least one gene encoding the [MEP/MVA] enzymes or a complementary gene thereof”; however, this is not clear in claim 1. Claim 1 recites “…the selection marker gene comprises at least one gene encoding the enzymes or a complementary gene thereof…”; however, is it unclear what enzymes Applicant is referring to and what “complementary genes thereof” means. Despite the lack of clarity, Won teaches complementary gene in the MVA pathway. Moreover, Won teaches that DNA encoding enzymes involved in the MVA pathway were introduced into the host cell, such as HMG-CoA synthase, HMG-CoA reductase, and mevalonate kinase, (see, e.g., Won, English translation, “Description”, pg. 3, [7]). Furthermore, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding Applicant’s argument that the proposed modification would render the prior art invention being modified unsatisfactory for its intended purposes (see remarks, pages 11-14), this argument is not persuasive for multiple reasons. First, the Broadest Reasonable Interpretation (BRI) of independent claim 1 is a non-human organism transformed with a plasmid encoding a target gene and a selection marker gene, wherein the non-human organism has enzymes within the isopentenyl diphosphate or dimethylallyl diphosphate synthetic pathway attenuated or deleted. Based on the BRI, the combined prior art of Won and Renninger teach the instantly claimed invention. Won teaches Escherichia coli as the host cell (see, e.g., Won, English translation, “Description”, pg. 3, [5]); Won teaches that genes encoding enzymes within the MEP pathway are inactivated within a host cell (see, e.g., Won, English translation, “Description”, pg. 3, [7]); Won teaches that DNA can be introduced into the host cell using a carrier, such as a plasmid (see, e.g., Won, English translation, “Description”, pg. 3, [8]); Won teaches the introduction of genes encoding enzymes within the MVA pathway (i.e., complementary genes) (see, e.g., Won, English translation, “Description”, pg. 3, [7]); Won teaches transforming the host cell with DNA encoding all enzymes related to a foreign mevalonic acid pathway (see, e.g., Won, English Translation, pg. 2, “Description”). Moreover, Renninger teaches that the host cells comprise enzymes of the MVA or MEP pathways (see, e.g., Renninger, [0066]-[0083]), as well as genes encoding enzymes which produce isoprenoids from isopentenyl diphosphate or dimethylallyl diphosphate (see, e.g., Renninger, [0084]-[0162]). Furthermore, Renninger teaches that nucleic acids can be introduced into the host cells by a single or multiple vectors (see, e.g., Renninger, [0164]) and selectable markers which do not rely on the use of antibiotics can be used to identify host cells which are successfully transformed (see, e.g., Renninger, [0047], [0172], [0184]-[0187], Examples 17-18). Therefore, the combined teachings of Won and Renninger teaches the instantly claimed invention. Secondly, Applicant’s arguments pertaining to test substances is not applicable to the claimed invention. Thirdly, Applicant’s argument that Won only teaches a host cell having an endogenous non-mevalonic acid pathway is not persuasive. Won teaches a host cell (i.e., E. coli) wherein the “intrinsic non-mevalonic acid pathway is inactivated and inhibits either or both the mevalonic acid pathway and the nonmevalonic acid pathway using a host cell transformed with DNA that encodes all enzymes involved in the foreign mevalonic acid pathway” (see, e.g., Won, English Translation, Description, pg. 2). It is unclear where Applicant is obtaining the idea that a host cell only having an endogenous non-mevalonic acid pathway is selected (it would be appreciated if Applicant could cite this). Based on the teachings of Won cited by the Examiner above, Won teaches host cells expressing a mevalonic acid pathway (MVA) or non-mevalonic acid pathway (methylerythritol 4-phostphate pathway; MEP), wherein one or more genes of the MEP pathway are inactivated (see, e.g., Won, English translation, abstract). Moreover, Won teaches that the MEP pathway is intrinsic to a host cell (see, e.g., Won, English translation, abstract). Furthermore, Won teaches a host cell having a non-mevalonic acid pathway, wherein one or more genes of the non-mevalonic acid pathway are inactivated, and wherein the host cell is transformed to express a foreign mevalonic acid pathway (see, e.g., Won, abstract). Therefore, based on the BRI of the instantly claimed invention, the combined prior art of Won and Renninger, as discussed above, teach the instantly claimed invention.
Conclusion
Claims 1-20 are rejected.
No claims are 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.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653