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 .
Election/Restrictions
Applicant’s election without traverse of the following species: (C) in claim 5; (C) in claim 6; claim 10 with YPC1 gene encoding a protein for production of PHS for claims 7 and 10; “modifying an expression control sequence of the gene encoding the protein” in claim 14; C18:0 PHS in claim 15 and cyclodextrin in claim 17 in the reply filed on 10/24/2025 is acknowledged.
Claims 7-9 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/24/2025.
Claims 1-22 are pending. Claims 1-6, 10, 11 and 13-22 (claim set filed 07/12/2023) are examined on the merits herein.
Priority
This application is a CON of PCT/JP2022/002034 filed 01/20/2022. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) based on application RUSSIAN FEDERATION 2021101096 filed 01/20/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) on 07/12/2023 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5 and 6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 5 recites the limitation for the protein encoded by the NEM1 gene to have 90% identity to the amino acid sequence of SEQ ID NO: 26 and function as a catalytic subunit of Nem1-Spo7 protein phosphatase. Claim 5 is interpreted as directed to the protein wherein 10% or less of the sequence vary from SEQ ID NO: 26 and the protein has activity of the catalytic subunit of Nem1-Spo7 protein phosphatase. Claim 6 recites the limitation for the protein encoded by the SPO7 gene to have 90% identity to the amino acid sequence of SEQ ID NO: 28 and function as a regulatory subunit of Nem1-Spo7 protein phosphatase. Claim 6 is interpreted as directed to the protein wherein 10% or less of the sequence vary from SEQ ID NO: 28 and the protein has activity of the regulatory subunit of Nem1-Spo7 protein phosphatase.
Thus, claim 5 broadly encompasses a genus of catalytic subunit of Nem1-Spo7 protein phosphatase with 90% or more sequence identity to SEQ ID NO: 26 and claim 6 broadly encompasses a genus of regulatory subunit of Nem1-Spo7 protein phosphatase with 90% or more sequence identity to SEQ ID NO: 28. This would represent large pools of variant amino acid sequences encoding the respective proteins which are functional. At the same time proteins can have 10% or less of sequences that can differ from SEQ ID NO: 26 and 28. The Specification does not provide structure function correlation for catalytic and regulatory subunits of Nem1-Spo7 protein and does not describe domains and/or amino acid residues essential for Nem1-Spo7 protein and domain and/or amino acid residues which can be modified without loss of Nem1-Spo7 protein function. Further, applicants have not shown possession of a representative number of species for the functional catalytic and regulatory subunits of Nem1-Spo7 protein as Specification provides only examples of deletion of NEM1 gene leading to non-functional Nem1-Spo7 protein (paragraph 0156). The specification describes that functional variants of Nem1-Spo7 protein can have conservative substitutions (paragraph 0068). However, even conservative mutations can lead to significant functional change. For instance, Mirheydari (Mirheydari et al. J. Biol. Chem, 2020, 295, 11473-11485) teaches domains of Nem1 and Spo7 and indicates serines as phosphorylation sites in both subunits phosphorylation of which by protein kinases A and C affect the New1-Spo7 function (p. 11475, Figure 2, p. 11473, right column, 2nd paragraph). Thus, conservative substitution of Ser of phosphorylation sites with Ala or Cys as described in the paragraph 0156 of the Specification will change the functioning of catalytic and regulatory subunits of Nem1-Spo7 protein.
Therefore, one of ordinary skill in the art would not be able to identify which polypeptide sequences that have 90% identity to SEQ ID NO:26 and SEQ ID NO:28 encode for functional catalytic and regulatory subunits of Nem1-Spo7 protein. One of ordinary skill in the art would conclude based on the lack of representative number of species and the lack of describing the domains or amino acid residues of SEQ ID NO: 26 and 28 critical for the function of catalytic and regulatory subunits of Nem1-Spo7 protein, that the Applicant was not in possession of the claimed genera and that the specification fails to satisfy the requirements of written description under 35 U.S.C. 112 (a). Therefore, claims 5 and 6 are rejected.
Claim 20 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the yeast to produce and accumulate the PHS in an amount larger when yeast is modified to reduce expression of NEM1 gene compared to unmodified yeast does not reasonably provide enablement for the yeast to produce and accumulate PHC with any modification of yeast and does not provide enablement for the yeast to produce and accumulate PHS in an amount larger when yeast is modified to reduce expression of SPO7 gene compared to unmodified yeast. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim 20 is directed to the yeast being able to produce and accumulate the objective substance in an amount larger than that with a non-modified yeast. Claim 20 is dependent on claim 1, reciting two objective substances, i.e. PHS and PHC and yeast modification of reducing expression and/or activity of a protein encoded by NEM1 and/or SPO7 genes.
The prior art of Schwab (WO 2017033463 A1 on record in IDS) teaches production of the objective substances in yeast including PHS and PHC (Abstract, paragraphs 0006, 0014) and describes reduction of the expression and/or activity of several proteins (paragraph 0006). However, Schwab does not teach modification of NEM1 or SPO7 genes and does not teach increase in the production of PHS and/or PHC with the modification of NEM1 or SPO7 genes.
Specification provides working example of increase in production of PHS with yeast modified by deletion of NEM1 gene (paragraph 0156). However, only one objective substance, i.e. PHS, was determined and production of PHC was not reported. Additionally, the Specification does not provide examples of production and accumulation of larger amount of either PHS or PHC in the yeast modified to reduce of expression and/or activity of SPO7 encoded protein.
Based on the unpredictability taught by the prior art and absence of working examples and directions provided by inventors, one of ordinary skill in the art would have to undergo undue experimentation to practice the full scope of the invention. Therefore, claim 20 is rejected under 35 U.S.C. 112(a) for failing to disclose sufficient supporting information to enable a person of skill in the art to use modification of SPO7 gene for increased production of PHS and to use modification of NEM1 and/or SPO7 genes for increased production of PHC.
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 1-6, 15-22 are rejected under 35 U.S.C. 103 as being unpatentable over Schwab (WO 2017033463 A1 on record in IDS) in view of Santos-Rosa (Santos-Rosa et al. The EMBO, 2005, 24, 1931-1941) as evidenced by Siniossoglou (Siniossoglou et al. The EMBO Journal, 1998, 17, 6449-6464), GenBank AAB6843.1 (GenBank, 2008, Yhr004cp [Saccharomyces cerevisiae] [retrieved on 12/26/2025]. Retrieved from the Internet: <Yhr004cp [Saccharomyces cerevisiae] - Protein - NCBI>) and GenBank AAC04949.1 (GenBank, 2004, Spo7p [Saccharomyces cerevisiae] [retrieved on 12/26/2025]. Retrieved from the Internet: <Spo7p [Saccharomyces cerevisiae] - Protein - NCBI>).
Regarding claim 1, Schwab teaches a method for producing an objective substance such as spingoid bases and sphingolipids by cultivating yeast in the presence of additive and collecting objective substance (Abstract). The spingoid bases include phytosphingosine (PHS) (paragraph 0013) and sphingolipids include phytoceramide (PHC) (paragraph 0014). Schwab describes modification of the yeast to reduce expression and/or activity of several proteins encoded by the corresponding genes, such as LCB4 (paragraph 0006).
Schwab does not teach modification of the yeast to reduce expression and/or activity of a protein encoded by NEM1 and/or SPO7.
Santos-Rosa teaches that Smp2, the yeast homologue of mammalian lipin, is a key regulator of nuclear membrane growth during cell cycle (Abstract). Santos-Rosa describes that Smp2 is phosphorylated by Cdc28/Cdka and dephosphorylated by phosphatase complex consisting of Nem1 and Spo7. The dephosphorylation of Smp2 inhibits cell division (Abstract). Santos-Rosa mentions that deletion of Nem1-Spo7 induces nuclear expansion (p. 1934, right column, last paragraph). Santos-Rosa discloses that accumulation of dephosphorylated Smp2 is toxic, results in significant increase of cells with short metaphase spindle and inhibits mitotic division (p. 1935, left column, 1st paragraph; p. 1939, left column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Schwab and Santos-Rosa and modify yeast used in the method of production of PHS and/or PHC taught by Schwab by reducing expression and/or activity of Nem1-Spo7 phosphatase described by Santos-Rosa. One would have been motivated to make this modification since Santos-Rosa teaches that Nem1-Spo7 dephosphorylate Smp2 that leads to inhibition of cell division and hence reduction of Nem1-Spo7 activity will provide proliferation of yeast necessary for production of the objective substance of Schwab teaching. A skilled artisan would have reasonably expected success in this combination because Schwab provides method of production of PHS and/or PHC in yeast and Santos-Rosa teaching suggests modification to improve yeast growth and proliferation. Thus, Schwab and Santos-Rosa teachings render claim 1 obvious.
Regarding claim 2, Santos-Rosa teaches that Nem1 and Spo7 form a complex and that both subunits are required for the catalytic activity against its substrate, Smp2 (p. 1938, right column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that reduction of the expression and/or activity of the catalytic subunit of Nem1-Spo7 protein, i.e. Nem1, is sufficient to reduce activity of Nem1-Spo7 phosphatase against Smp2 and provide cell proliferation. One would have been motivated to make assumption with the reasonably expected success because Santos-Rosa teaches that both subunits of Nem1-Spo7 are required for the catalytic activity of Nem1-Spo7. Thus, Schwab and Santos-Rosa teachings render claim 2 obvious.
Regarding claims 3 and 4, Schwab teaches that modification of the yeast to reduce activity of the protein modified can be attained by reducing expression of the gene encoding the protein (paragraph 0079) or disrupting the gene (paragraph 0081). Schwab mentions that disruption of the gene can be done by deleting part or the whole coding region of the gene (paragraph 0082).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to reduce activity of Nem1 and or Spo7 by reducing expression or disrupting the genes encoding these proteins. One would have been motivated to do that with the reasonably expected success because Schwab teaches different techniques for reduction of expression and disruption of several genes and the same techniques can be applied to NEM1 and SPO7 genes. Thus, teachings of Schwab and Santos-Rosa render claims 3 and 4 obvious.
Regarding claims 5 and 6, Santos-Rosa teaches that Nem1 is the catalytic subunit and Spo7 is the regulatory subunit of Nem1-Spo7 holoenzyme (p. 1934, left column, 1st paragraph). Santos-Rosa refers to identification of Nem1 and Spo7 proteins in prior art of Siniossoglou (p. 1932, left column, 2nd paragraph). The identified Nem1 and Spo7 proteins have the GenBank accession No. 500822 for NEM1 and GenBank accession No 349744 for SPO7 as evidenced by Siniossoglou (p. 6450, right column, 1st paragraph). The GenBank accession No. 500822 provides amino acid sequence for the protein encoded by NEM1 gene which is 100% identical to instant SEQ ID NO: 26 according to BLAST analysis as evidenced by GenBank AAB6831.1. The GenBank accession No. 349744 provides amino acid sequence for the protein encoded by SPO7 gene which is 100% identical to instant SEQ ID NO: 28 according to BLAST analysis as evidenced by GenBank AAC04949.1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Santos-Rosa teaching and use genes NEM1 and SPO7 encoding amino acid sequences for Nem1 and Spo7 proteins which are 100% identical to instant SEQ ID NO: 26 and SEQ ID NO: 28, respectively, as evidenced by Siniossoglou, GenBank AAB6831.1 and GenBank AAC04949.1 for modification of the yeast producing PHS and/or PHC based on Schwab and Santos-Rosa teachings. One would have been motivated to do that since GenBank AAB6831.1 and GenBank AAC04949.1 provide amino acid sequences identified by Siniossoglou and used by Santos-Rosa and Santos-Rosa teaches that Nem1 is the catalytic subunit and Spo7 is the regulatory subunit of Nem1-Spo7 phosphatase that dephosphorylates Smp2 that leads to inhibition of cell division and hence modification of the yeast by reduction of Nem1-Spo7 activity will provide proliferation of yeast necessary for production of the objective substances. A skilled artisan would have reasonably expected success in that because Schwab provides method of production of PHS and/or PHC in yeast, Santos-Rosa teaching suggests modification to improve yeast growth and proliferation and Siniossoglou, GenBank AAB6831.1 and GenBank AAC04949.1 provide sequences of Nem1 and Spo7 for modification. Thus, teachings of Schwab and Santos-Rosa as evidenced by Siniossoglou, GenBank AAB6831.1 and GenBank AAC04949.1 render claims 5 and 6 obvious.
Regarding claim 15, Schwab teaches phytosphingosine C18 PHS which has a saturated C18 alkyl chain (paragraph 0013) that corresponds to claimed C18:0 PHS (elected species) since the Specification describes that C18:0 PHS has saturated C18 alkyl chain (paragraph 0033). Thus, teachings of Schwab and Santos-Rosa render claim 15 obvious.
Regarding claims 16 and 17, Schwab teaches that the culture medium contains an additive that is able to associate with, bind to, solubilize and/or capture the objective substance (paragraph 0006). The additive includes cyclodextrin (elected species) (paragraph 0006). Thus, teachings of Schwab and Santos-Rosa render claims 16 and 17 obvious.
Regarding claims 18 and 19 Schwab teaches the yeast to belong to Saccharomyces and being Saccharomyces cerevisiae (paragraph 0006). Thus, teachings of Schwab and Santos-Rosa render claims 18 and 19 obvious.
Regarding claim 20, Santos-Rosa teaches that Nem1-Spo-7 dephosphorylate Smp2 and that can inhibit cell division as described above for claim 1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the yeast modification of reduction of the expression and/or activity of Nem1-Spo7 protein phosphatase will increase the level of produced and accumulated objective substance. One would have been motivated to make assumption with the reasonably expected success because Santos-Rosa teaches that dephosphorylation of Smp2 by Nem1-Spo7 can result in inhibition of cell division and hence reduction of Nem1-Spo7 can support yeast cells growth and proliferation and increase production of objective substance by method taught by Schwab. Thus, Schwab and Santos-Rosa teachings render claim 20 obvious.
Regarding claim 21, Schwab teaches collecting the objective substance from cells of the yeast and/or culture medium (paragraph 0006). Thus, teachings of Schwab and Santos-Rosa render claim 21 obvious.
Regarding claim 22, Schwab teaches producing sphingoid base (which is PHS as described in the Specification (paragraph 0033)) and converting it to PHC by chemical reaction of sphingoid base and fatty acid (paragraph 0109). Thus teachings of Schwab and Santos-Rosa render claim 22 obvious.
Claims 10, 11, 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Schwab (WO 2017033463 A1 on record in IDS) in view of Santos-Rosa (Santos-Rosa et al. The EMBO, 2005, 24, 1931-1941) as applied to claim 1 above, and further in view of Obeid (Obeid et al. Biochim. Biophys. Acta, 2002, 1585, 163-171).
The teachings of Schwab and Santos-Rosa have been set forth above.
Schwab and Santos-Rosa do not teach modification of the yeast to increase expression and/or activity of the protein encoded by YPC1 for production of PHS (elected species).
Regarding claims 10 and 11, Obeid teaches metabolism and biology of yeast sphingolipids (Abstract). Obeid describes that ceramides, sphingoid bases and their phosphates can be generated from breakdown of sphingolipids (p. 167, right column, 3rd paragraph). Obeid discloses that yeast YPC1p is a phytoceramidase that preferentially hydrolyzes phytoceramide (PHC) (p. 165, right column, 4th paragraph). Obeid mentions that PHS can be generated from de novo or breakdown pathway, i.e. from hydrolysis of phytoceramide by phytoceramidase encoded by YPC1 (p. 167, right column, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow guidance of Obeid and further modify the yeast producing PHS based on Schwab and Santos-Rosa teachings by increasing expression of phytoceramidase encoded by YPC1. One would have been motivated to do that since Obeid teaches that PHS can be generated by hydrolysis of phyroceramide which is the preferential reaction catalyzed by phytoceramidase encoded by YPC1 gene and increased expression of YPC1 gene will lead to increased production of PHS. A skilled artisan would have reasonably expected success in this combination because Schwab provides method of production of PHS in yeast, Santos-Rosa teaching suggests modification to improve yeast growth and proliferation and Obeid teaching points to further yeast modification to add PHS produced by phytoceramide hydrolysis to de novo production of PHS. Thus, Schwab, Santos-Rosa and Obeid teachings render claims 10 and 11 obvious.
Regarding claims 13 and 14, Schwab teaches that modification of the yeast to increase activity of the protein modified can be attained by increasing expression of the gene encoding the protein (paragraph 0056). Schwab mentions that expression of the gene can be increased by improving the transcription efficiency of the gene and transcription efficiency can be improved by modifying an expression control sequence of the gene (paragraph 0066). Schwab provides description of several strong promoters that can be used to increase transcriptional efficiency (paragraph 0067).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to increase activity of phytoceramidase by increasing expression of YPC1 gene encoding phytoceramidase and increase expression by modifying an expression control sequence of the gene as described by Schwab. One would have been motivated to do that with the reasonably expected success because Schwab provides instructions to increase expression of gene of interest including modification of the expression control sequence of the gene and the same techniques can be applied to YPC1 gene. Thus, teachings of Schwab, Santos-Rosa and Obeid render claims 13 and 14 obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 10, 11, 13-19, 21 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, 11-15, 18 and 20 of copending Application No. 18/351,225 (reference application) in view of Santos-Rosa (Santos-Rosa et al. The EMBO, 2005, 24, 1931-1941).
Claim 1 of instant application is directed to a method for producing an objective substance comprising cultivating yeast to produce the objective substance which is selected from PHS and PHC wherein the yeast is modified to reduced expression and/or activity of a protein encoded by NEM1 and/or SPO7. Claim 1 of reference application teaches a method for producing an objective substance comprising cultivating yeast to produce the objective substance in a medium containing a fatty acid wherein the objective substance is selected from PHS and PHC.
Regarding claim 1, reference claim 1 does not teach modification of the yeast to reduce expression and/or activity of a protein encoded by NEM1 and/or SPO7. Regarding fatty acid in the medium of the reference claim, instant claim 1 had “comprising” language for the method that does not exclude presence of additional components in the medium.
Santos-Rosa teaches that Smp2, the yeast homologue of mammalian lipin, is a key regulator of nuclear membrane growth during cell cycle (Abstract). Santos-Rosa describes that Smp2 is phosphorylated by Cdc28/Cdka and dephosphorylated by phosphatase complex consisting of Nem1 and Spo7. The dephosphorylation of Smp2 inhibits cell division (Abstract). Santos-Rosa mentions that deletion of Nem1-Spo7 induces nuclear expansion (p. 1934, right column, last paragraph). Santos-Rosa discloses that accumulation of dephosphorylated Smp2 is toxic, results in significant increase of cells with short metaphase spindle and inhibits mitotic division (p. 1935, left column, 1st paragraph; p. 1939, left column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine claim 1 of reference teaching and Santos-Rosa teaching and modify yeast in the method of production of PHS and/or PHC taught by claim 1 by reducing expression and/or activity of Nem1-Spo7 phosphatase described by Santos-Rosa. One would have been motivated to make this modification since Santos-Rosa teaches that Nem1-Spo7 dephosphorylates Smp2 that leads to inhibition of cell division and hence reduction of Nem1-Spo7 activity will provide proliferation of yeast necessary for production of the objective substance of reference claim 1 teaching. A skilled artisan would have reasonably expected success in this combination because reference claim 1 provides method of production of PHS and/or PHC in yeast and Santos-Rosa teaching suggests modification to improve yeast growth and proliferation. Thus, claim 1 of reference application and Santos-Rosa teachings render claim 1 obvious.
Claims 10 and 11 of instant application are drawn to further modification of the yeast producing PHS to increase expression and/or activity of the protein encoded by YPC1 gene (elected species). That correspond to claim 7 of reference application.
Claim 13 of instant application is drawn to increase in activity of the protein by increasing the expression of the gene encoding the protein. That correspond to claim 8 of reference application.
Claim 14 of instant application is drawn to increase in expression and/or activity of the protein by modifying an expression control sequence of the gene encoding the protein (elected species). That correspond to claim 9 of reference application.
Claim 15 of instant application is drawn to selection of PHS including C18:0 PHS (elected species). That correspond to claim 11 of reference application.
Claim 16 of instant application is drawn to an additive that is able to associate with, bind to, solubilize, and/or capture the objective substance. That correspond to claim 12 of reference application.
Claim 17 of instant application is drawn to selected additive which is cyclodextrin (elected species). That correspond to claim 13 of reference application.
Claim 18 of instant application is drawn to the yeast belonging to Saccharomyces. That correspond to claim 14 of reference application.
Claim 19 of instant application is drawn to the yeast being Saccharomyces cerevisiae. That correspond to claim 15 of reference application.
Claim 21 of instant application is drawn to collecting the objective substance from cells of the yeast and/or from the culture medium. That correspond to claim 18 of reference application.
Claim 22 of instant application is drawn to producing PHC comprising producing PHS and converting it to the PHC. That correspond to claim 20 of reference application.
Therefore, since instant claims 1, 10, 11, 13-19, 21 and 22 encompass the subject matter of the reference claims 1, 7-9, 11-15, 18 and 20, they are rejected under obviousness double patenting.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G 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.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653