Prosecution Insights
Last updated: July 17, 2026
Application No. 18/252,001

RECOMBINANT MICROORGANISM, PREPARATION METHOD THEREFOR, AND APPLICATION OF RECOMBINANT MICROORGANISM IN PRODUCTION OF TAGATOSE

Non-Final OA §103§112
Filed
May 05, 2023
Priority
Nov 05, 2020 — CN 202011224203.0 +1 more
Examiner
REGLAS, GEORGIANA C
Art Unit
1651
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Tiangong Biotechnology (Tianjin) Co. Ltd.
OA Round
1 (Non-Final)
38%
Grant Probability
At Risk
1-2
OA Rounds
4m
Est. Remaining
68%
With Interview

Examiner Intelligence

Grants only 38% of cases
38%
Career Allowance Rate
27 granted / 71 resolved
-22.0% vs TC avg
Strong +30% interview lift
Without
With
+30.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 7m
Avg Prosecution
31 currently pending
Career history
120
Total Applications
across all art units

Statute-Specific Performance

§101
2.1%
-37.9% vs TC avg
§103
62.2%
+22.2% vs TC avg
§102
3.3%
-36.7% vs TC avg
§112
6.6%
-33.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 71 resolved cases

Office Action

§103 §112
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/Restriction Applicant's election with traverse of Group I, claims 1-5 and the species of possessing all characteristics of (a)-(c), characteristic (d) of claim 3, and SEQ ID NO: 1, 5, 7, 9, and 13 in the reply filed on 10/13/2025 is acknowledged. The traversal is on the ground(s) that, inter alia, “the Examiner misidentified the “linking” feature that unifies all the claims [i.e., the requirement fails to recognize the true linking feature – the cooperative interplay of (a)-(c) as recited in claim 1]; the requirement rests on premature examination on the merits, and the Examiner has not established a serious search burden and examination as required by the MPEP” and that the cited reference Ma does not disclose or suggest this specific three-way combination, the action implicitly evaluates whether the linking feature is patentable over Ma, etc.. This is not found persuasive because the technical feature under consideration when the Restriction requirement was made was “a recombinant microorganism wherein the microorganism has at least one of the features (a)-(c) as compared to a wildtype microorganism”. Ma explicitly teaches a recombinant microorganism overexpressing tagatose phosphate epimerase enzyme and tagatose-6-phosphate phosphorylase (see claims 1-7, para 11-18 and SEQ ID NO: 1-4). Thus, the claim was found to lack a special technical feature distinguished over the prior art. Second, there is nothing in the restriction requirement that “implicitly evaluates whether the alleged linking feature is patentable over Ma” (see pg. 4 of the response). Applicant is reminded of the requirement for unity of invention under PCT Rule 13.1 and 13.2: the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. Thus, the feature common to all claims (at least enhanced tagatose phosphate epimerase), i.e., the technical feature, does not make a contribution over the prior art and cannot be considered a special technical feature under PCT Rule 13.2. Hence, the requirement is still deemed proper and is therefore made FINAL, as Applicant cannot amend the claim to overcome initial grounds upon which a lack of unity of invention was made and supported. Claims 6-8 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/13/2025. Priority The instant application claims benefit to PCT Application No. PCT/CN2021/124427 (filed 10/18/2021) and CN202011224203.0 (filed on 11/05/2020) and is acknowledged. The instant claims herein are examined using the effective filing date of 11/05/2020 for the basis of any prior art rejections. Information Disclosure Statement The information disclosure statement(s) (IDS) submitted on 05/23/2023 and 02/28/2025 were properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) were considered. Nucleotide and/or Amino Acid Sequence Disclosures Summary of Requirements for Patent Applications Filed on Or After July 1, 2022, That Have Sequence Disclosures 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted: 1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying: a. the name of the XML file b. the date of creation; and c. the size of the XML file in bytes; or 2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying: a. the name of the XML file; b. the date of creation; and c. the size of the XML file in bytes. SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS: Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing. Required response - Applicant must: • Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of: • A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); • A copy of the amended specification without markings (clean version); and • A statement that the substitute specification contains no new matter. Specification The abstract of the disclosure is objected to because it contains legal phraseology throughout. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. Claim interpretation Instant claim 2 requires, inter alia, “wherein the glucose- specific transfer protein is selected from the group shown in any one the following (a1)-(a3): (a1) a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 and having glucose-specific transfer protein activity; . . . optionally, the tagatose-6-phosphate epimerase is selected from the group shown in any of the following (b1)-(b3). . . . optionally, the tagatose-6-phosphate phosphatase is selected from the group shown in any of the following (c1)-(c3)” (emphasis added). Instant claim 4 also recites the same “optionally” language as it relates to featured (e1)-(e3). The examiner has interpreted the claims under broadest reasonable interpretation such that the limitations after the term “optionally” are not required by the instant claims, such that claim 2 requires, inter alia, any one of features (a1)-(a3) and claim 4 only requires any one of features (d1)-(d3). Claim Rejections - 35 USC § 112(b) The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claims 2 and 4 are 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. The claims recite “an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3”, “an amino acid sequence obtained by substituting, repeating, deleting or adding one or more amino acids to the amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3”, “a polypeptide having an amino acid sequence obtained by substituting, repeating, deleting or adding one or more amino acids to the amino acid sequence as set forth in SEQ ID NO: 5”, etc. (see claim 2), and the same for SEQ ID NO: 9-15 (see claim 4). It is unclear whether the claims require any amino acid sequence derived from the claimed SEQ IDs (i.e., “comprising the amino acid sequence set forth in. . .” [open language]), or only the amino acid sequences claimed (i.e., “consisting of the amino acid sequence set forth in. . .” [closed language]). Thus, the claims are indefinite. For the purposes of compact patent prosecution, the examiner is interpreting the claims under broadest reasonable interpretation to be “comprising” the claimed SEQ IDs (i.e., open language). Claim Rejections - 35 USC § 112(a) 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 1-5 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 claim(s) 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. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted)."). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed. Claim interpretation: The claims require, inter alia, “A recombinant microorganism, wherein the recombinant microorganism has all of the following characteristics (a)-(c), as compared to a wild- type microorganism: (a) reduced or lost protein activity of glucose-specific transfer protein of phosphotransferase system and/or expression level of its coding gene; (b) enhanced enzyme activity of tagatose-6-phosphate epimerase and/or expression level of its coding gene; (c) enhanced enzyme activity of tagatose-6-phosphate phosphatase and/or expression level of its coding gene.” Claim 2 requires, inter alia, “the glucose-specific transfer protein is selected from the group shown in any one the following (a1)-(a3): (a1) a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 and having glucose-specific transfer protein activity; (a2) a polypeptide having an amino acid sequence obtained by substituting, repeating, deleting or adding one or more amino acids to the amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, and having glucose-specific transfer protein activity. . .”. Claim 3 requires “(d) enhanced enzyme activity of glucokinase and/or expression level of its coding gene; (e) enhanced enzyme activity of glucose-6-phosphate isomerase and/or expression level of its coding gene; (f) reduced or lost enzyme activity of fructose-6-phosphate kinase and/or expression level of its coding gene; (g) reduced or lost enzyme activity of pyruvate kinase and/or expression level of its coding gene; (h) reduced or lost enzyme activity of phosphoglucomutase and/or expression level of its coding gene; (i) reduced or lost enzyme activity of glucose-6-phosphate dehydrogenase and/or expression level of its coding gene; (j) reduced or lost enzyme activity of HPr kinase and/or expression level of its coding gene”. Claim 4 requires, inter alia, “the glucokinase is selected from the group shown in any one of the following (d1)-(d3): (d1) a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 9 or SEQ ID NO: 11 and having glucokinase activity; (d2) a polypeptide having an amino acid sequence obtained by substituting, repeating, deleting or adding one or more amino acids to the amino acid sequence as set forth in SEQ ID NO:9 or SEQ ID NO: 11, and having glucokinase activity. . .” The examiner has interpreted the above limitations under broadest reasonable interpretation (BRI) to encompass at least one mutation (e.g., 2, 3, 10, 40 mutations) anywhere within the amino acid sequence of SEQ ID NO: 1, 3, 5, 9, 11, etc. (substitution, deletion, etc.) and still retain glucose specific transfer activity (see (a2) in claim 2) or glucokinase activity (see (d2) in claim 4). The question at issue is whether the skilled artisan would understand the correlation between structure of the broad genus of mutated polypeptides and ability to retain their functional capacities as instantly claimed, as there is no correlation or defining characteristic that would convey the identity of the structures necessary to perform the claimed functions. Reduction to practice and disclosure of drawings or structural chemical formulas: Applicant discloses in the specification the stepwise creation of various E. coli recombinant mutant strains (YH1, YH2, YH3-1, 4-1, 5-1, 6-1, MG1655-1, YH1-1 through 6-2) (see Examples 1-14) and recombinant B. subtilis strains (YJ8-14, SKC6-1, YJ8-1 through 14-1; see Examples 15-28), each mutant containing single and/or successive amplification of, inter alia, tagatose epimerase activity, glucokinase,glucose-6-phosphate isomerase, pyruvate kinase, phosphoglucomutase, glucose-6-phosphate dehydrogenase, etc., as well as mutations to knock out the PTS system glucose-specific transfer protein coded by ptsG (see the Examples provided in the Specification). However, the Specification fails to demonstrate the massive genus of mutations of any kind (addition, substitution, duplication, deletion, etc.) within the claimed sequences, and failed to demonstrate that the mutations would result in polypeptides that continue to retain glucose specific transfer protein activity and glucokinase activity as instantly claimed. Sufficient, relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure: Applicant has not provided information as to the defining structural characteristics that would lead one of ordinary skill in the art to the identity of a mutations would result in polypeptides that continue to retain glucose specific transfer protein activity and glucokinase activity as instantly claimed. Applicants are claiming, essentially, any mutation along the sequence of SEQ ID NO: 1, 3, 9, 11, etc. (additions, substitutions, deletions, etc.) that would impart these functions onto the enzymes. This means that the polypeptide mutants have functional limitations of glucose specific transfer protein activity and glucokinase activity compared to the wildtype protein. However, under broadest reasonable interpretation, the enzyme can encompass any mutated sequence or portion thereof, but Applicants have not disclosed which portion of the enzymes are necessary for the functional limitation as claimed. Even with knowledge in the art regarding the mutation of amino acids, one of ordinary skill would not know what structural features are required for the outcome of conferring glucose specific transfer protein activity and glucokinase activity in the proteins without a recognized correlation between structure and function. In essence, Applicants are describing a critical portion of their invention by function. This is not sufficient to meet the written description requirement. Thus, the data generated for the creation of the specific recombinant E. coli and B. subtilis mutants described in the specification cannot reasonably be extrapolated to and applied to support possession of the entire claimed genus of polypeptide as claimed, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966). The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the claimed genus of subject(s) in need thereof, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the claimed genus. Therefore, the claims are rejected under 35 U.S.C. 112(a) for lack of written description. 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. First rejection Claims 1, 3, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al (CN109666620A; cited in Applicant IDS; hereinafter “Ma”), in view of Ma et al (CN109750024B; published 05/14/2019; hereinafter “Ma2”) and Chou et al. (Effect of modified glucose uptake using genetic engineering techniques on high-level recombinant protein production in Escherichia coli dense cultures. Biotechnol Bioeng. 1994 Oct;44(8):952-60; hereinafter “Chou”). Note that an English translation of the Ma2 reference is provided with the instant rejection. Ma teaches a recombinant microorganism that overexpresses tagatose phosphate epimerase for tagatose production via fermentation (enhanced enzyme activity of tagatose-6-phosphate epimerase as in claim 1; see claims 1-7, paragraphs 11-18; abstract, throughout disclosure). Ma does not explicitly teach enhanced enzyme activity of tagatose-6-phosphate phosphatase. However, Ma2 teaches the creation of a recombinant host cell that contains a multi-enzymatic vector system including epimerase and tagatose 6 phosphate phosphatase (T6P) for the successful production of tagatose from the host cell (see examples 3-5; pg. 4-5). Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the recombinant microorganism of Ma with the enhanced expression of tagatose-6phosphate phosphatase as taught by Ma2 to arrive at the claimed invention. One of ordinary skill would have been motivated to make the modification because Ma2 explicitly teaches that recombinant microorganisms expressing the tagatose-6-phosphate-phosphatase are advantageously capable of successfully producing tagatose from starch. Neither reference teaches reduced or lost protein activity of glucose-specific transfer protein of the phosphotransferase system. However, Chou teaches the effect of modified glucose uptake using genetic engineering techniques on high-level recombinant protein production in E. coli (see title, abstract). Chou teaches and Escherichia coli strain bearing a ptsG- mutation (i.e., a deletion of ptsG), a gene encoding enzyme II in glucose phosphotransferase system (PTS) was constructed and while the growth rate of the mutant strain was slower than its parent in glucose, it showed a significant improvement in culture performance in simple batch cultivations due to reduced acetate excretion through the modified glucose uptake, had biomass and recombinant protein productivity increased by more than 50% with the ptsG mutant when compared to the parent strain (see abstract, throughout; Fig. 2-3; pg. 956-57). Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the recombinant microorganism of Ma and Ma2 with the ptsG mutation as taught by Chou to arrive at the claimed invention. One of ordinary skill would have been motivated to make the modification because Chou explicitly teaches that reducing or knockout of ptsG that encodes enzyme II of the PTS system advantageously allows significant improvement in culture performance in simple batch cultivations due to reduced acetate excretion through the modified glucose uptake, biomass and increase in recombinant protein productivity by more than 50% with the ptsG mutant when compared to the parent strain. Regarding claim 3, Ma teaches enhancing the enzymatic activity of glucokinase (see abstract, throughout). Regarding claim 5, Ma teaches the tagatose engineered strain is suitable for Corynebacterium glutamicum, Escherichia coli, and Bacillus subtilis (see claim 4; throughout). Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary. Second rejection Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Ma, Ma2, and Chou as applied to claim 1, 3, and 5 above, and further in view of PTS glucose transporter subunit IIBC [Escherichia coli] WP_128475401.1; available online 23 Jan 2019; retrieved from https://www.ncbi.nlm.nih.gov/protein/1561176354?sat=47&satkey=58884767. As discussed above, 1, 3, and 5 claims were rendered prima facie obvious by the combined teachings of Ma, Ma2, and Chou. As further discussed above, Chou explicitly teaches ptsG gene mutation encoding enzyme II of the PTS system advantageously allows significant improvement in culture performance in simple batch cultivations due to reduced acetate excretion through the modified glucose uptake, biomass and increase in recombinant protein productivity by more than 50% with the ptsG mutant when compared to the parent strain. None of the references explicitly teach that the protein is a polypeptide comprising an amino acid sequence of SEQ ID NO: 1. However, WP_128475401.1 teaches a PTS glucose transporter protein encoding enzyme II of the PTS system (see below). WP_128475401.1 teaches an amino acid sequence of the transporter protein that has 99.6% sequence identity to SEQ ID NO 1. PNG media_image1.png 232 655 media_image1.png Greyscale PNG media_image2.png 1277 1109 media_image2.png Greyscale Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the recombinant microorganism of Ma, Ma2, and Chou by mutating the protein disclosed by WP_128475401.1 to arrive at the claimed invention. One of ordinary skill would have been motivated to make the modification especially in view of Chou, which explicitly discloses that mutation of this protein in recombinant microorganisms advantageously leads to significant improvement in culture performance in simple batch cultivations due to reduced acetate excretion through the modified glucose uptake, biomass and increase in recombinant protein productivity by more than 50% with the ptsG mutant. Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary. Third rejection Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Ma, Ma2, and Chou as applied to claim 1, 3, and 5 above, and further in view of Uniprot Accession number A0A0E0XW57_ECO1C (see STIC/ABSS search 06/22/2026 result 1). As discussed above, the claims were rendered prima facie obvious by the combined teachings of Ma, Ma2, and Chou. As further discussed above, Ma teaches mutating the recombinant microorganism regulating the intracellular metabolism of glucose, and enhances the enzymatic activities of glucokinase and glucose 6-phosphate isomerase to increase the content of intracellular fructose 6-phosphate that will lead to enhanced tagatose production (see abstract; throughout). None of the references teach that the glucokinase is a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 9. However, A0A0E0XW57_ECO1C teaches a glucokinase from E. coli; the glucokinase of ECO1C has 100% sequence identity with instant SEQ ID NO 9 (see below alignment). PNG media_image3.png 1045 520 media_image3.png Greyscale Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the recombinant microorganism of Ma, Ma2, and Chou by enhancing the expression of the protein as disclosed by A0A0E0XW57_ECO1C to arrive at the claimed invention. One of ordinary skill would have been motivated to make the modification especially in light of the explicit teachings of Ma, which explicitly discloses that enhancement of the expression of this protein in recombinant microorganisms advantageously allows increase the content of intracellular fructose 6-phosphate that will lead to enhanced tagatose production (see abstract; throughout). Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary. Conclusion NO CLAIMS ALLOWED. Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm. 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, Melenie Gordon can be reached at 571-272-8037. 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. /G.C.R./Examiner, Art Unit 1651 /THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
Read full office action

Prosecution Timeline

May 05, 2023
Application Filed
Mar 13, 2026
Response after Non-Final Action
Jun 26, 2026
Non-Final Rejection mailed — §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
38%
Grant Probability
68%
With Interview (+30.5%)
3y 7m (~4m remaining)
Median Time to Grant
Low
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Based on 71 resolved cases by this examiner. Grant probability derived from career allowance rate.

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