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 claims 10-15 in the reply filed on 6/9/2026 is acknowledged.
Claims 1-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/9/2026.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Taiwan on 5/29/2024. It is noted, however, that applicant has not filed a certified copy of the TW113119768 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 7/3/2025 and 10/2/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Examiner’s Suggestion
Claim 10 is directed to “A method for converting a carbon source into ethylene glycol, characterized in that the carbon source is converted into the ethylene glycol by using modified cyanobacteria”. The examiner suggests using a traditional transitional phrase (see MPEP 2111.03). The examiner suggests amending claim 10 to replace “characterized in that” with the transitional phrase “comprising”.
As applicant is clearly claiming a method, the claims are not rejected under 35 U.S.C. § 112(b) according to MPEP 2173.05(q). Although the term “using” is broad, it is not indefinite. However, the examiner suggests amending claim 10 to replace “using modified cyanobacteria” with “the modified cyanobacteria convert”.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 10 and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Koch et al., US 2020/0283806 A1.
Regarding claim 10, Koch teaches a method of producing monoethylene glycol, MEG, using recombinant microorganisms comprising one or more biochemical pathways that produces MEG (Koch p. 1 para. 2, p. 114 para. 1591). Koch teaches that the microorganism may be cyanobacteria (Koch p. 7 para. 75). Koch teaches that the method of producing MEG comprises culturing the recombinant organism containing a feedstock providing a carbon source until MEG is produced (Koch p. 96 para. 1325). Koch teaches that the recombinant microorganism for the production of MEG comprises enzymes for the production of MEG through the conversion of DHAP or pyruvate in a C3 pathway, wherein the enzymes have 3-phosphoglycerate dehydrogenase activity, a phosphoserine aminotransferase activity, a phosphoserine phosphatase activity, glycolaldehyde reductase activity, a serine decarboxylase activity, and ethanolamine oxidoreductase activity (Koch pp. 116-117 para. 1645).
Instant SEQ ID NO: 1 encodes ethanolamine oxidase (Tyna); instant SEQ ID NO: 2 encodes glycolaldehyde reductase (YghD/YqhD); instant SEQ ID NO: 3 encodes serine decarboxylase (SDC); instant SEQ ID NO: 4 encodes 3-phosphoglycerate dehydrogenase (SerA); instant SEQ ID NO: 5 encodes phosphoserine phosphatase (SerB); and instant SEQ ID NO: 6 encodes phosphoserine aminotransferase (SerC) (see instant specification para. 41; sequence alignment in OA appendix). Koch teaches that the enzyme having ethanolamine oxidase activity may be E. coli tynA (Koch p. 47 para. 660); that the enzyme having glycolaldehyde reductase activity may be yqhD (Koch p. 75 para. 1042); that the enzyme having serine decarboxylase activity may be Arabidopsis thaliana SDC (Koch p. 47 para. 653); that the enzyme having 3-phosphoglycerate dehydrogenase activity is serA from E. coli (Koch p. 76 para. 1043); that the enzyme having phosphoserine aminotransferase activity is serC from E. coli (Koch p. 76 para. 1044); and that the enzyme having phosphoserine phosphatase activity is serB from E. coli (Koch p. 76 para. 1047).
Koch does not teach that the modified microorganism includes the gene sequences of SEQ ID NOs: 1-6 as set forth in claim 10.
However, as discussed above, the gene sequences of SEQ ID NOs: 1-6 encode the proteins Tyna, YqhD, SDC, SerA, SerB, and SerC. All of these proteins are known in the art and genes encoding these proteins are expressed in modified microorganisms as taught by Koch. While the gene sequences taught by Koch are not the same as instant SEQ ID NOs: 1-6, a skilled artisan would be aware of the degeneracy of the genetic code, wherein multiple DNA codons encode for a single amino acid (Koch p. 112 para. 1570). Thus, there are numerous gene sequences that can encode for the same protein. Further, as taught by Koch, most organisms typically use only a subset of the 64 possible codons, with codons being used in particular organisms known as optimal codons (Koch p. 112 para. 1570). Koch teaches that codons can be optimized to reflect the preferred codon usage of the host, and that optimized codon sequences can be prepared by known techniques to produce transcripts with desirable properties (Koch p. 112 para. 1570-1571). Koch teaches that those of skill in the art will recognize that, due to the degenerate nature of the genetic code, a variety of nucleic acid sequences can be used to encode a given enzyme of the disclosure, and the disclosure includes any nucleic acid sequences that encode the amino acid sequences of the polypeptides and proteins of the enzymes of the present disclosure (Koch p. 112 para. 1572).
Thus, a skilled artisan would have been aware that numerous gene sequences encode the proteins as taught by Koch, and would have found it obvious, through the process of routine optimization, to modify the gene sequence according to the optimal codon preferences of the host microorganism. It would have been obvious to arrive at sequences according to instant SEQ ID NOs: 1-6, which encode the same genes as set forth in Koch, given the known degeneracy of the genetic code and the known techniques for codon optimization.
Regarding claim 12, Koch teaches that the carbon source includes glucose, fructose, and sucrose (Koch p. 96 para. 1326).
Regarding claim 13, Koch teaches that the modified microorganism, which may be a cyanobacterium, is capable of producing serine decarboxylase which catalyzes the conversion of L-serine to ethanolamine (Koch p. 46 para. 652).
Regarding claim 14, Koch teaches that the modified microorganism, which may be a cyanobacterium, is capable of producing ethanolamine oxidase, which catalyzes the conversion of ethanolamine to glycolaldehyde (Koch p. 47 para. 659).
Regarding claim 15, Koch teaches that the modified microorganism, which may be a cyanobacterium, is capable of producing glycolaldehyde reductase, which catalyzes the conversion of glycolaldehyde to ethylene glycol (Koch p. 74 para. 1018).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Koch et al., US 2020/0283806 A1 as applied to claims 10 and 12-15 above, and further in view of Vogel et al., Journal of biological engineering. 2017 Jun 5;11(1):19.
The method of claim 10 is obvious in view of Koch, as set forth above. Koch does not teach that the genomic DNA of the modified cyanobacteria includes a first locus and a second locus, the gene sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 are located at the first locus, and the gene sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 are located at the second locus (claim 11).
Regarding claim 11, Vogel teaches neutral integration sites for recombination-mediated
genetic engineering of the cyanobacterium Synechococcus sp. (Vogel Abstract). Vogel teaches that the ability of cyanobacteria to utilize sunlight for capturing CO2 makes them powerful cell factories, and cyanobacteria can be genetically engineered to produce industrially relevant chemicals such as isobutanol, sucrose, hydrogen, and ethylene (Vogel p. 1 “Background” para. 1). Vogel teaches that Synechococcus sp. PCC 7002 is an excellent chassis for biotechnological applications as it can utilize high-light irradiation and grow with a short doubling time, and can grow photoautotrophically, mixotrophically or heterotrophically and tolerates a wide range of temperatures and salt concentrations (Vogel pp. 1-2 “Background” para. 3). Vogel teaches that Synechococcus can incorporate dsDNA in its genome via homologous recombination (Vogel p. 2 para. 2). Vogel teaches that neutral integration sites (loci) for standardized integration of non-native genes are an important tool for efficient genomic engineering (Vogel p. 2 para. 3). Vogel teaches three neutral integration loci, wherein genes can be integrated without a negative impact on the cell (Vogel p. 4 “Neutral integration sites in Synechococcus sp. PCC 7002”).
It would have been obvious for a skilled artisan to combine the teachings of Koch and Vogel, arriving at a method of producing ethylene glycol using a modified cyanobacterial cell wherein the gene sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 are located at a first locus and the gene sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 are located at a second locus. Vogel teaches that cyanobacteria have numerous sites (i.e, a locus) wherein an exogenous gene can be integrated without negative impact to the cell, known as neutral sites. Koch teaches modifying bacteria, including cyanobacteria, to express genes in the biosynthetic pathways for ethylene glycol production, as discussed above. Koch teaches expression of exogenous genes using techniques known in the art, such as integration of vectors into the host chromosome (Koch p. 112 para. 1569). It would have been obvious for a skilled artisan to incorporate the genes for ethylene glycol production taught by Koch into one or more known neutral sites, or loci, in cyanobacteria.
Further, it would have been obvious to incorporate SEQ ID NOs: 1, 2, and 3 at one locus, and SEQ ID NOs: 4, 5, and 6 at another locus. SEQ ID NOs: 1, 2, and 3 encode ethanolamine oxidase, glycolaldehyde reductase, and serine decarboxylase. These enzymes are utilized in the pathway from the precursor L-serine to ethylene glycol, catalyzing subsequent reactions generating ethanolamine, glycolaldehyde, and ethylene glycol, as discussed above regarding claims 14-16 (see Koch Fig. 10). SEQ ID NOs: 4, 5, and 6 encode serA, serB, and serC, which are enzymes in the L-serine biosynthesis pathway, catalyzing subsequent reactions generating 3P-HPyr, 3P-Ser, and L-serine to obtain the precursor L-serine (see Koch Fig. 10; pp. 80-81 para. 1100-1104). Thus, a skilled artisan would have found it obvious to construct a strain wherein the serine biosynthesis genes are integrated at one locus and the genes for converting the serine precursor to ethylene glycol are at a different locus.
A skilled artisan would have been motivated to introduce SEQ ID NOs: 1, 2, and 3 at one locus and SEQ ID NOs: 4, 5, and 6 at another locus because Vogel teaches that the length of the insert of exogenous DNA at neutral sites in cyanobacteria affects transformation efficiency, with an increase of 2-3 kb in exogenous DNA insert length decreasing transformation efficiency by half in one study (Vogel p. 7 “Further optimization of the transformation” para. 1). SEQ ID NO: 1 is 2274 bp, SEQ ID NO: 2 is 1164 bp, and SEQ ID NO: 3 is 1449 bp, for a total of 4887 bp, or 4.87 kb. SEQ ID NO: 4 is 1590 bp, SEQ ID NO: 5 is 1338 bp, and SEQ ID NO: 6 is 1080 bp, for a total of 4008 bp, or 4.008 kb. Thus, as larger insert sizes have been shown to be detrimental to transformation efficiency, a skilled artisan would have been motivated to insert the groups of genes at different loci to avoid the problem of a larger insert leading to decreased transformation efficiency.
A skilled artisan would have had a reasonable expectation of success in creating a cyanobacterial strain with SEQ ID NOs: 1, 2, and 3 at one locus and SEQ ID NOs: 4, 5, and 6 at another locus, because Koch teaches strains wherein the proteins encoded by SEQ ID NOs: 1-6 are integrated, and Vogel teaches that there are known sites and techniques for integrating exogenous genes into cyanobacterial genomes. Thus, a person having ordinary skill in the art could expect success in integrating these sets of genes at two different loci in a cyanobacterial cell, wherein each of the loci are known to be sites that tolerate exogenous DNA integration.
Conclusion
Claims 10-15 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY F EIX/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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