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 01/02/2026 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minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments.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Briefly, the previous claim rejections under 35 U.S.C. 112(b) for indefiniteness have been withdrawn necessitated by Applicant’s amendments. The previous claim rejections under 35 U.S.C. 101 for non-statutory subject matter have been withdrawn necessitated by Applicant’s amendments.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Priority
The instant application filed on 12/15/2022 is a 371 of PCT/JP2021/022884 filed on 06/16/2021, which claims priority to JP2020-104487 filed on 06/17/2020 and JP2020-169550 filed on 10/07/2020. The Office has received the certified English translations for the foreign priority documents filed on 01/02/2026. JP2020-104487 finds support for the instantly claimed invention; therefore, the effective filing date of the instant application is 06/17/2020.
Maintained Rejections
Claim Rejections - 35 USC § 112(a), Written Description
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.
Claims 2-3, 5, and 14-17 are rejected under 35 U.S.C. 112(a) 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.
Claim 2 includes “The transformant according to claim 1, wherein the aspartate dehydrogenase gene is a DNA selected from…(2) DNA, which consists of a base sequence having 90% or more identity to any one of SEQ ID NOs: 1 to 11, and which encodes a polypeptide having aspartate dehydrogenase activity” and “(5) DNA, which encodes a polypeptide consisting of an amino acid sequence having 90% or more identity to any one of SEQ ID NOs: 16 to 26, and the polypeptide having aspartate dehydrogenase activity. Claim 3 includes “The transformant according to claim 1, wherein the aspartate dehydrogenase gene is a DNA selected from… (2) DNA, which consists of a base sequence having 90% or more identity to SEQ ID NO: 3, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 11, and encodes a polypeptide having aspartate dehydrogenase activity” and “(5) DNA, which encodes a polypeptide consisting of an amino acid sequence having 90% or more identity to SEQ ID NO: 18, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 26, and the polypeptide having aspartate dehydrogenase activity”. The instant Specification states “The aspartate dehydrogenase gene used in the present invention may be a DNA, which consists of a base sequence having 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98%or more, or 99% or more identity to any of SEQ ID NOs: 1 to 12, and encodes a polypeptide having aspartate dehydrogenase activity. The aspartate dehydrogenase gene used in the present invention is preferably a DNA, which consists of a base sequence having 90% or more identity to SEQ ID NO: 3, 8, 9, or 11, and encodes a polypeptide having aspartate dehydrogenase activity. In the present invention, the identity of a base sequence can be determined using any method known to a person skilled in the art and can be calculated using, for example, GENETYX ver.17 (manufactured by Genetics Corporation)” (see, e.g., instant Spec, [0015]). Moreover, the instant Specification states “The aspartate dehydrogenase gene introduced in the present invention may be, for example, a DNA consisting of the base sequence of the aspartate dehydrogenase gene derived from Candidatus Hydrothermae bacterium (SEQ ID NO: 1), the base sequence of the aspartate dehydrogenase gene derived from Glaciecola sp. 33A (SEQ ID NO: 2), the base sequence of the aspartate dehydrogenase gene derived from Mesorhizobium sp. M7D.F.Ca.US.005.01.1.1 (SEQ ID NO: 3), the base sequence of the aspartate dehydrogenase gene derived from Rhodospirillaceae bacterium (SEQ ID NO: 4), the base sequence of the aspartate dehydrogenase gene derived from Bacillus kochii (SEQ ID NO: 5), the base sequence of the aspartate dehydrogenase gene derived from Novosphingobium rosa (SEQ ID NO: 6), the base sequence of the aspartate dehydrogenase gene derived from Archaeoglobus fulgidus (SEQ ID NO: 7), the base sequence of the aspartate dehydrogenase gene derived from Arthrobacter sp. 161MFSha2.1 (SEQ ID NO: 8), the base sequence of the aspartate dehydrogenase gene derived from Oceanotoga teriensis (SEQ ID NO: 9), the base sequence of the aspartate dehydrogenase gene derived from Marinitoga sp. 1155 (SEQ ID NO: 10), the base sequence of the aspartate dehydrogenase gene derived from Thermotogales bacterium 46_20 (SEQ ID NO: 11), or the base sequence of the aspartate dehydrogenase gene derived from Thermoga maritima (SEQ ID NO: 12)” (see, e.g., instant Spec, [0014]). The Examiner has interpreted this to mean that there is no necessary core structure and/or sequence needed for the DNA or polypeptide to contain to exhibit aspartate dehydrogenase activity. As such, the scope of the claimed DNA or polypeptide encompasses a large array of DNA or polypeptide without any necessary core structure and/or sequence needed in order for the polypeptide to exhibit the claimed aspartate dehydrogenase activity. Furthermore, in regards to claim 5, the instant Specification states that for the TH-1C strain “The plasmid vector pCAMO-4 was cleaved with the restriction enzymes NdeT and NotI and ligated with the DNA fragment of the prepared AspDH synthesis gene using T4 DNA ligase (manufactured by Takara Bio Co., Ltd.). The endogenous plasmid was removed from the Hydrogenophilus thermoluteolus TH-1 strain by a conventional method to obtain a curing strain (TH-1C strain)” (see, e.g., instant Spec, [0041]).
The written description may be met by providing a representative number of species of the genus and/or in light of the state of the art. In regards to the state of the art, Li (Discovery of novel highly active and stable aspartate dehydrogenases; 2017) teaches that aspartate dehydrogenases contain two discernable domains: N-terminal domain (residue 1–105) and C-terminal domain (residue 113–241). N-terminal domain contains a typical Rossmann fold, the protein motif which is predicted to bind coenzymes like NAD+, NADP+ or FAD (see, e.g., Li, Discussion, pg. 5). Yang (Aspartate Dehydrogenase, a Novel Enzyme Identified from Structural and Functional Studies of TM1643; 2003) teaches TM1643, which is an aspartate dehydrogenase protein, and further teaches “The active site of TM1643 is located at the interface between the N- and C-terminal domains of the monomer. Residues in this active site come from strands 7 and 10, helices A, F, and G, the 5-C loop and the E-F loop, and finally the linker between the two domains (residues 106–112) (Fig. 4A). They are generally well conserved among this family of proteins (Fig. 1). There is a clear depression on the surface of the protein, delineating the region for substrate binding and catalysis (Fig. 4B). This active site region is open to the solvent in the current structure (Fig. 4B). It is expected that the active site will be shielded from the solvent in the closed form of the enzyme when the substrate is bound. Our structural analysis showed that the His-193 residue may function as the general acid/base in the catalysis by these enzymes. This residue is strictly conserved among all family members and may be located near the C4 position of the nicotinamide ring in the closed form of the enzyme. In support of this observation, the His-193 residue is structurally equivalent to the catalytic His residue in ASA-DH (19). A short loop of the enzyme, residues 212–219 (just prior to helix G, Figs. 2A and 3A), is disordered in our current structure. These residues may be located in the active site, helping form a flap over the active site when the substrate is bound” (see, e.g., Yang, “The Active Site of TM1643”, pgs. 8806-8807). Thus, the state of the art recognizes various active site/core residues for aspartate dehydrogenases, each of which do not share a common core structure and/or sequence that a polypeptide would need to exhibit the claimed aspartate dehydrogenase activity. Moreover, regarding the TH-1C strain, the prior art does not teach this strain, nor does the prior art provide a sequence for this strain.
Alternatively, the written description may be met by providing a representative number of species of the genus. Instant claim 2 recites “DNA, which consists of a base sequence having 90% or more identity to any one of SEQ ID NOs: 1 to 11” and “DNA, which encodes a polypeptide consisting of an amino acid sequence having 90% or more identity to any one of SEQ ID NOs: 16 to 26”. Instant claim 3 recites “DNA, which consists of a base sequence having 90% or more identity to SEQ ID NO: 3, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 11” and “DNA, which encodes a polypeptide consisting of an amino acid sequence having 90% or more identity to SEQ ID NO: 18, SEQ ID NO: 23, SEQ ID NO: 24, or SEQ ID NO: 26”. This accounts for up to 10% variation in SEQ ID NO: 1 (up to 78 nucleic acid variation), SEQ ID NO: 2 (up to 79 nucleic acid variation), SEQ ID NO: 3 (up to 77 nucleic acid variation), SEQ ID NO: 4 (up to 80 nucleic acid variation), SEQ ID NO: 5 (up to 78 nucleic acid variation), SEQ ID NO: 6 (up to 77 nucleic acid variation), SEQ ID NO: 7 (up to 71 nucleic acid variation), SEQ ID NO: 8 (up to 81 nucleic acid variation), SEQ ID NO: 9 (up to 76 nucleic acid variation), SEQ ID NO: 10 (up to 75 nucleic acid variation), SEQ ID NO: 11 (up to 74 nucleic acid variation), SEQ ID NO: 16 (up to 26 amino acid variation), SEQ ID NO: 17 (up to 26 amino acid variation), SEQ ID NO: 18 (up to 25 amino acid variation), SEQ ID NO: 19 (up to 26 amino acid variation), SEQ ID NO: 20 (up to 26 amino acid variation), SEQ ID NO: 21 (up to 25 amino acid variation), SEQ ID NO: 22 (up to 23 amino acid variation), SEQ ID NO: 23 (up to 26 amino acid variation), SEQ ID NO: 24 (up to 25 amino acid variation), SEQ ID NO: 25 (up to 25 amino acid variation), and SEQ ID NO: 26 (up to 24 amino acid variation). Therefore, the instant Specification fails to demonstrate a representative number of nucleic acid and amino acid species so that one of ordinary skill in the art can extrapolate to the claimed genus. Additionally, the instant Specification does not set forth a core structure or core residues within the nucleic acid or polypeptide sequences that exhibit aspartate dehydrogenase activity. Thus, the specific embodiments taught in the instant Specification are not sufficient for the skilled artisan to envisage what constitutes a necessary core structure and/or sequence for a nucleic acid or polypeptide that exhibits aspartate dehydrogenase activity. Moreover, regarding the TH-1C strain, the instant Specification does not provide a sequence for this strain, and merely provides one sentence on how the TH-1C strain is produced (see, e.g., instant Specification, [0041]). Thus, the written description provided pertaining to the TH-1C strain is not sufficient for the skilled artisan to envisage what constitutes the TH-1C strain.
Accordingly, claims 2-3, 5, and 14-17 do not meet the written description requirement. Claims 14-17 depend on rejected claims 2-3 and fail to rectify the noted deficiencies.
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the 112(a), written description rejection (remarks, pages 6-7), Applicant does not provide a representative number of species to extrapolate to the claimed genus. As stated above, 90% or more sequence identity results in 10% variation within the sequences. This accounts for up to 10% variation in SEQ ID NO: 1 (up to 78 nucleic acid variation), SEQ ID NO: 2 (up to 79 nucleic acid variation), SEQ ID NO: 3 (up to 77 nucleic acid variation), SEQ ID NO: 4 (up to 80 nucleic acid variation), SEQ ID NO: 5 (up to 78 nucleic acid variation), SEQ ID NO: 6 (up to 77 nucleic acid variation), SEQ ID NO: 7 (up to 71 nucleic acid variation), SEQ ID NO: 8 (up to 81 nucleic acid variation), SEQ ID NO: 9 (up to 76 nucleic acid variation), SEQ ID NO: 10 (up to 75 nucleic acid variation), SEQ ID NO: 11 (up to 74 nucleic acid variation), SEQ ID NO: 16 (up to 26 amino acid variation), SEQ ID NO: 17 (up to 26 amino acid variation), SEQ ID NO: 18 (up to 25 amino acid variation), SEQ ID NO: 19 (up to 26 amino acid variation), SEQ ID NO: 20 (up to 26 amino acid variation), SEQ ID NO: 21 (up to 25 amino acid variation), SEQ ID NO: 22 (up to 23 amino acid variation), SEQ ID NO: 23 (up to 26 amino acid variation), SEQ ID NO: 24 (up to 25 amino acid variation), SEQ ID NO: 25 (up to 25 amino acid variation), and SEQ ID NO: 26 (up to 24 amino acid variation). Applicant has not provided a representative number of species for these nucleic acid and amino acid sequences, wherein these sequences still encode polypeptides having aspartate dehydrogenase activity. Therefore, one of ordinary skill in the art would not readily know or understand what nucleic acids and/or amino acids can be manipulated and still read on the claimed invention. Moreover, even if the core amino acids are known for L-aspartate dehydrogenase, and if the variation is not within the core amino acids, one of ordinary skill in the art would not readily know or understand from the instant specification what other amino acids outside the core structure can or cannot be manipulated because the instant specification does not set forth a representative number of species. For example, 10% sequence variation in SEQ ID NO: 1 would result in up to 78 nucleic acid variation, which is 26 amino acids. There is no guidance in the instant specification on which 26 amino acids can be manipulated. Moreover, even if the core amino acids are known, based on Applicant’s arguments, it is still unknown which 26 amino acids outside the core structure can or cannot be manipulated and which still read on the claim. Moreover, Applicant does not provide arguments or evidence that nucleic acid and/or amino acid variation outside the core structure would affect aspartate dehydrogenase activity. Therefore, based on the guidance set forth in the instant specification, Applicant does not provide a representative number of species that would guide one of ordinary skill in the art to understand what amino acids and/or nucleic acids can or cannot be manipulated within these sequences.
Maintained Rejections
Claim Rejections - 35 USC § 112(a), Enablement
Claim 5 is rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The invention appears to employ novel biological materials, specifically a Hydrogenophilus thermoluteolus TH-1C. Since the biological materials are essential to the claimed invention they must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If the biological materials are not so obtainable or available, the requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the biological materials.
If the deposit is made under the Budapest Treaty, then an affidavit or declaration by Applicant, or a statement by an attorney of record over his or her signature and registration number, stating that the specific biological materials have been deposited under the Budapest Treaty and that the biological materials will be irrevocably and without restriction or condition released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein. If the deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 C.F.R. § 1.801-1.809, Applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, showing that:
during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer;
a test of the viability of the biological material at the time of deposit will be made (see 37 C.F.R. § 1.807); and
the deposit will be replaced if it should ever become inviable.
Applicant's attention is directed to M.P.E.P. § 2400 in general, and specifically to MPEP § 2411.05, as well as to 37 C.F.R. § 1.809(d), wherein it is set forth that "the specification shall contain the accession number for the deposit, the date of the deposit, the name and address of the depository, and a description of the deposited material sufficient to specifically identify it and to permit examination.” The specification should be amended to include this information; however, Applicant is cautioned to avoid the entry of new matter into the specification by adding any other information.
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the 112(a), enablement rejection (remarks, pages 7-8), as discussed above, Applicant relies on novel biological materials, specifically a Hydrogenophilus thermoluteolus TH-1C, within the claimed invention, which must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If the biological materials are not so obtainable or available, the requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the biological materials. It is understood that the TH-1 strain, which the TH-1C strain is produced from, is available to the public; however, Applicant produced the novel TH-1C strain for this invention by removing endogenous plasmids from the TH-1 strain. Therefore, the requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the biological materials, and Applicant must provide assurance of compliance.
Maintained Rejections
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, 4, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Kuvaeva (JP 2013/516958; Date of Publication: May 16, 2023 – cited in the IDS filed on 03/07/2023) in view of Hideaki (WO 2019/207812; Date of Publication: October 31, 2019 – cited in the IDS filed on 03/07/2023).
Kuvaeva’s general disclosure relates a bacterium belonging to the Enterobacteriaceae family that produces L-aspartate or metabolites derived from L-aspartate that have been modified to have aspartate dehydrogenase activity, as well as L-aspartic acid and metabolites derived from L-aspartic acid such as L-threonine, L-lysine, L-arginine, L-methionine, and L-homoserine (see, e.g., Kuvaeva, English Translation, abstract & claim 1, pgs. 1-2).
Regarding claim 1 pertaining to the transformant and aspartate dehydrogenase gene, Kuvaeva teaches the production of a bacterial transformant belonging to the Enterobacteriaceae family, wherein the bacterium has been transformed by introducing a gene encoding an aspartate dehydrogenase (see, e.g., Kuvaeva, English Translation, pg. 2, claims 1-2).
Regarding claim 12 pertaining to the production of aspartic acid, Kuvaeva teaches that the transformant produces L-aspartic acid (see, e.g., Kuvaeva, English Translation, pg. 2, claim 17).
Regarding claim 13 pertaining to the production of methionine, Kuvaeva teaches that the transformant produces L-methionine (see, e.g., Kuvaeva, English Translation, pg. 2, claim 19).
However, Kuvaeva does not teach: a Hydrogenophilus bacterium (claim 1); or wherein the Hydrogenophilus bacterium is Hydrogenophilus thermoluteolus (claim 4).
Hideaki’s general disclosure relates to “a hydrogenophilus bacterium transformant having the ability to produce isobutanol, ethanol, or alanine” (see, e.g., Hideaki, English Translation, “Description”, pg. 5). Moreover, Hideaki discloses a transformant that is obtained by introducing DNA encoding 2-keto acid decarboxylase, and a gene encoding alcohol dehydrogenase to Hydrogenophilus bacteria in order to efficiently produce isobutanol using carbon dioxide as the only source of carbon (see, e.g., Hideaki, English Translation, abstract).
Regarding claims 1 and 4 pertaining to the bacterium, Hideaki teaches that the transformant is Hydrogenophilus thermoluteolus (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20). Hideaki teaches that Hydrogenophilus thermoluteolus is used as the host for production of the transformant because Hydrogenophilus thermoluteolus has a “top-level growth rate as a carbonic acid-fixing microorganism, and thus has a carbonic acid-fixing ability” (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20), which one of ordinary skill in the art would understand is important when producing isobutanol. Moreover, Hydrogenophilus thermoluteolus can easily be isolated from anywhere on earth (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20).
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 bacterial transformant by introducing an aspartate dehydrogenase gene, as taught by Kuvaeva, wherein the bacterium is Hydrogenophilus thermoluteolus, as taught by Hideaki. One would have been motivated to do so because Hideaki teaches that Hydrogenophilus thermoluteolus can easily be isolated from anywhere on earth (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20). Hideaki also teaches that Hydrogenophilus thermoluteolus is used as the host for production of the transformant because Hydrogenophilus thermoluteolus has a “top-level growth rate as a carbonic acid-fixing microorganism, and thus has a carbonic acid-fixing ability” (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20); therefore, one of ordinary skill in the art would readily understand that the carbon obtained from this bacteria can be used in a variety of biological processes. Moreover, Kuvaeva teaches increasing the expression of L-aspartic acid, or metabolites derived from L-aspartic acid, by an Enterobacteriaceae bacterium that is transformed with an aspartate dehydrogenase gene (see, e.g., Kuvaeva, English Translation, abstract & claim 1, pgs. 1-2). Therefore, based on the teachings of Kuvaeva and Hideaki, it would have been obvious to substitute the bacterium belonging to the family Enterobacteriaceae with Hydrogenophilus thermoluteolus because Hydrogenophilus thermoluteolus can be isolated from anywhere on earth and therefore is widely abundant. One would have expected success because Kuvaeva and Hideaki both teach the production of transformants that are transformed to express different enzymes to manipulate biological pathways.
Claims 2-3 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kuvaeva and Hideaki as applied to claims 1, 4, and 12-13 above, and further in view of Dietrich (WO 2017/083683; Date of Publication: May 18, 2017).
The teachings of Kuvaeva and Hideaki, herein referred to as modified-Kuvaeva-Hideaki, are discussed above as it pertains to a Hydrogenophilus bacterium transformant that expresses an aspartate dehydrogenase gene.
Regarding claims 14 and 16 pertaining to the production of aspartic acid, Kuvaeva teaches that the transformant produces L-aspartic acid (see, e.g., Kuvaeva, English Translation, pg. 2, claim 17).
Regarding claim 15 and 17 pertaining to the production of methionine, Kuvaeva teaches that the transformant produces L-methionine (see, e.g., Kuvaeva, English Translation, pg. 2, claim 19).
However, modified-Kuvaeva-Hideaki does not teach: DNA, which encodes a polypeptide consisting of an amino acid sequence having a deletion, substitution, or addition of one or more amino acids in SEQ ID NO: 18 (claims 2-3).
Dietrich’s general disclosure relates to the biological production of L-aspartate and/or beta-alanine under substantially anaerobic conditions (see, e.g., Dietrich, abstract). Moreover, Dietrich discloses that yeast is used as a host cell and can comprise heterologous nucleic acids expressing L-aspartate dehydrogenase in order to produce L-aspartate (see, e.g., Dietrich, [0008]-[0009]).
Regarding claims 2-3 pertaining to part 6, Dietrich teaches SEQ ID NO: 25, which encodes an L-aspartate dehydrogenase from Ruegeria pomeroyi, and which has 32.6% sequence similarity to instant SEQ ID NO: 18 (see, e.g., Office Action Appendix). Moreover, Dietrich’s SEQ ID NO: 25 consists of deletions, substitutions, and additions of one or more amino acids in instant SEQ ID NO: 18 (see, e.g., Office Action Appendix).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce modified-Kuvaeva-Hideaki’s transformant, wherein the transformant consists of Dietrich’s SEQ ID NO: 25 encoding L-aspartate dehydrogenase from Ruegeria pomeroyi. One would have been motivated to do so because Dietrich teaches that L-aspartate dehydrogenase from Ruegeria pomeroyi is capable of producing L-aspartate under anaerobic conditions (see, e.g., Dietrich, [0009]). Additionally, Dietrich teaches “Conversion of oxaloacetate to L-aspartate is catalyzed by L-aspartate dehydrogenase (EC 1.4.1.21)” (see, e.g., Dietrich, [0016]). Moreover, modified-Kuvaeva-Hideaki teaches that L-amino acids have been industrially produced by fermentation methods; therefore, microorganisms have been transformed to recombinantly produce L-amino acids, such as L-aspartate (see, e.g., Kuvaeva, “Description”, pg. 2). Moreover, modified-Kuvaeva-Hideaki teaches modifying Enterobacteriaceae to express aspartate dehydrogenase in order to enhance production of L-aspartate by the bacterium (see, e.g., Kuvaeva, “Description”, pg. 3). Therefore, based on the teachings of modified-Kuvaeva-Hideaki and Dietrich, it would have been obvious to produce a transformant that expresses Dietrich’s SEQ ID NO: 25 since this encodes an aspartate dehydrogenase. One would have expected success because modified-Kuvaeva-Hideaki and Dietrich both teach production of transformants expressing aspartate dehydrogenase to produce L-aspartate.
Examiner’s Response to Arguments
Applicant's arguments filed 01/02/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments pertaining to the difference in bacterial properties (remarks, pages 8-9), this argument is not persuasive for multiple reasons:
First, claims are examined based on their broadest reasonable interpretation (BRI) (see, e.g., MPEP 2111). For independent claim 1, this is a product-by-process claim; therefore, patentability is based on the product itself (see, e.g., MPEP 2113). Therefore, based on the BRI for independent claim 1, this claim merely pertains to a transformant, which is anticipated by Kuvaeva. However, since structure is implied in claim 1’s product-by-process limitation, the Examiner set forth the teachings of Hideaki to teach the Hydrogenophilus thermoluteolus bacterium.
Secondly, since structure is implied in claim 1’s product-by-process limitation, the claim would read on a Hydrogenophilus thermoluteolus bacterium transformed with an aspartate dehydrogenase gene, which is rendered obvious by the teachings of Kuvaeva and Hideaki. As discussed above, Kuvaeva teaches the production of a bacterial transformant belonging to the Enterobacteriaceae family, wherein the bacterium has been transformed by introducing a gene encoding an aspartate dehydrogenase (see, e.g., Kuvaeva, English Translation, pg. 2, claims 1-2). Moreover, Hideaki teaches that Hydrogenophilus thermoluteolus can be used as the transformant because Hideaki teaches that this bacterium can be transformed with other genes, such as the gene encoding 2-keto acid decarboxylase (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20). Therefore, Hideaki was cited as evidence and motivation that Hydrogenophilus thermoluteolus can be used as the bacterial host and can be transformed. Moreover, Kuvaeva was cited for teaching transformation of the aspartate dehydrogenase gene into bacteria. One would have been motivated to use Hydrogenophilus thermoluteolus as the host cell because Hydrogenophilus thermoluteolus can easily be isolated from anywhere on earth (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20). Hideaki also teaches that Hydrogenophilus thermoluteolus has a “top-level growth rate as a carbonic acid-fixing microorganism, and thus has a carbonic acid-fixing ability” (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20). Furthermore, one would have been motivated to transform the aspartate dehydrogenase gene because transformation of the aspartate dehydrogenase gene into a bacterium allow for expression of L-aspartic acid, or metabolites derived from L-aspartic acid, by a bacterium that is transformed with an aspartate dehydrogenase gene (see, e.g., Kuvaeva, English Translation, abstract & claim 1, pgs. 1-2). Therefore, one of ordinary skill in the art would have been motivated to combine the teachings of Kuvaeva and Hideaki if one wanted to produce a transformed Hydrogenophilus thermoluteolus bacterium, that inherently has the properties of Hydrogenophilus thermoluteolus, and which expresses aspartate dehydrogenase for the production of L-aspartic acid or metabolites derived from L-aspartic acid.
Fourthly, based on the BRI of independent claim 1, Applicant does not claim a specific aspartate dehydrogenase that is to be transformed into the Hydrogenophilus thermoluteolus bacterium. Therefore, this aspartate dehydrogenase can be from Thermotoga maritima, which, as taught by Kuvaeva, “can catalyze the positive reaction of aspartate synthesis from oxaloacetate and ammonia in vitro. By utilizing this reaction for aspartic acid synthesis, it can be easier to avoid the by-production of glutamic acid. On the other hand, the authors aspartic acid suggest that the role of this enzyme in vivo is to convert aspartic acid to iminoaspartic acid, a precursor of NAD aspartic acid aspartic acid biosynthesis. Furthermore, it has been shown that aspartate dehydrogenase from T. maritima has a high optimum temperature (+ 70 ° C.) and only a low residual activity at + 30 ° C. to + 40 ° C (see, e.g., Kuvaeva, English Translation, “Description”, pg. 3). This is further motivation to transform Hydrogenophilus thermoluteolus with aspartate dehydrogenase from Thermotoga maritima.
Fifthly, the Examiner does not mention the use of Enterobacteriaceae as the bacterium in the above rejection; therefore, Applicant’s argument regarding the use of Enterobacteriaceae is not persuasive. Instead, as discussed previously, the art of Kuvaeva was used to teach that the aspartate dehydrogenase gene from Thermotoga maritima can be transformed into a bacterium, and Hideaki teaches Hydrogenophilus thermoluteolus as the bacterium.
Regarding Applicant’s arguments pertaining to the difference in metabolic pathways (remarks, page 9), this argument is not persuasive based on the responses above. In short, as discussed above, the Examiner set for the teachings of Kuvaeva to show that Kuvaeva teaches that bacteria can be transformed with a gene encoding for aspartate dehydrogenase, and one would have been motivated to transform and express the gene encoding for an aspartate dehydrogenase because this would allow for the transformed bacterium to produce L-aspartic acid and metabolites derived from L-aspartic acid (see, e.g., Kuvaeva, English Translation, “Description”, pg. 3). Moreover, the teachings of Hideaki were set forth to show that Hideaki teaches that Hydrogenophilus thermoluteolus can be transformed and the motivation to use Hydrogenophilus thermoluteolus is because this bacterium can easily be isolated from anywhere on earth (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20) and has a “top-level growth rate as a carbonic acid-fixing microorganism, and thus has a carbonic acid-fixing ability” (see, e.g., Hideaki, English Translation, “Method for producing transformant”, pg. 20). Therefore, one of ordinary skill in the art would have been motivated to combine the teachings of Kuvaeva and Hideaki to teach a Hydrogenophilus thermoluteolus bacterium transformed with a gene expressing aspartate dehydrogenase in order to produce a bacterium that has the inherent properties of Hydrogenophilus thermoluteolus, but that can also produce L-aspartic acid and metabolites derived from L-aspartic acid.
Regarding Applicant’s remarks pertaining to the teachings of Dietrich, this argument is not persuasive because the BRI of dependent claims 2-3, part 6 pertains to a polypeptide that can have one or more deletions, substitutions, or additions of amino acids. Therefore, based on the BRI of these claims, these polypeptide sequences can have as little as one amino acid different, or all amino acid s different, when compared to SEQ ID NOs: 16-26 (claim 2), or when compared to SEQ ID NOs: 18, 23, 24, or 26 (claim 3). Based on this, Dietrich teaches SEQ ID NO: 25, which encodes an L-aspartate dehydrogenase from Ruegeria pomeroyi, and which has 32.6% sequence similarity to instant SEQ ID NO: 18 (see, e.g., Office Action Appendix). Moreover, Dietrich’s SEQ ID NO: 25 consists of deletions, substitutions, and additions of one or more amino acids in instant SEQ ID NO: 18 (see, e.g., Office Action Appendix). As shown in the Office Action Appendix, there are 29 conservative substitutions and 112 mismatches due to substitutions. Therefore, based on the interpretation set forth above, Dietrich reads on claims 2-3, part 6.
Conclusion
Claims 1-3, 5, and 12-17 are rejected. Claim 5 is free from the art because the art does not teach the TH-1C strain.
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.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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