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 .
Status of the Claims
Claims 1-5, 7-8, and 10-27 are pending (claim set as filed on 07/01/2026).
Priority
This application is a 371 of PCT/US2023/062467, which is a CON of application no.: 17/671,029 filed on 02/14/2022.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 05/18/2026 and 09/03/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Withdrawal of Rejections
The response and amendments filed on 07/01/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s response to arguments section.
Briefly, the previous anticipation and double patenting rejections over Yoon (US 2022/0325235 A1 and co-pending application no. 17/635,144) have been withdrawn necessitated by Applicant’s amendment to include the enzymes of BCAT1 and ADH5 in the base claims. Yoon does not teach the enzymes species of BCAT1 nor ADH5.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New Grounds of Rejection Necessitated by Amendment
Claim Rejections - 35 USC §112(d), Failing to Further Limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4 and 19 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 recites, in part, the specific enzyme specie of “BCAT1” from a list of alternatives. However, its base claim 1 (as amended) already requires the enzyme to be BCAT1 and therefore, the scope of dependent claim 4 as it pertains to the BCAT1 does not further limit its base claim. In other words, the species BCAT1 would be duplicated in scope if selected.
Claim 19 recites, in part, the specific enzyme specie of “ADH5” from a list of alternatives. However, base claim 16 already requires the enzyme to be ADH5 and therefore, the scope of dependent claim 19 as it pertains to the ADH5 does not further limit its base claim. In other words, the species ADH5 would be duplicated in scope if selected.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper
dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
New Grounds of Rejection Necessitated by Amendment and IDS
Claim Rejections - 35 USC §102, Anticipation
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 7-8, and 10-27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuang (Metabolic By-Product Identification, Pathway Analysis and Control Through Metabolomics Study in CHO Cell Culture, 2021 – cited in the IDS filed on 09/03/2026).
Kuang teaches “an LCMS-based metabolomics pipeline was utilized to screen CHO cellular metabolites accumulating in the cell supernatants. A total of eight metabolites produced through CHO ce1ls metabolism were identified and characterized” (see abstract)
Kuang teaches cell culturing of CHO cells in a culture media (see page 6: Section 2.1 Cell Culture). Kuang teaches identifying the metabolites including trigonelline (TRI), cytidine 5’-monophosphate (CMP), 2-hydroxyisocaproic acid (HICA), aconitic acid (ACA), methylsuccinic acid (MSA), N-acetylputrescine (NAP), et. al. (see page 14: Table I-6. Metabolites spiking list). At page 92, Kuang teaches “genes were inserted into plasmids and transiently transfected into cells when cells reached viable cell density of 1x106 cells·mL-1
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Kuang teaches “Chinese Hamster Ovary (CHO) cells are used extensively at commercial scale to produce a majority of therapeutic proteins, such as monoclonal antibodies” (see page 1: Background).
Kuang teaches cell culture to fed-batch and perfusion (see page 1: Background).
Kuang teaches LC-MS (Liquid Chromatography - Mass Spectroscopy) represents a powerful tool for providing a broad metabolite snapshot of cells at any point of time during cell culture (see page 2, last ¶).
Double Patenting
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 1-5, 7-8, and 10-27 are rejected on the ground of non-statutory double patenting as being unpatentable over at least claims 1-15 of now U.S. Patent no. 12,703,851 B2 (parent application no. 17/671,029). Although the claims at issue are not identical, they are not patentably distinct from each other because patent ‘851 is the narrower claim set that anticipates the instant claims:
Regarding claims 1, 4-5, 16, and 19 patent ‘851 teaches “A method of cell culture comprising (i) culturing mammalian cells in a cell culture medium, and (ii) maintaining at least one metabolite below an inhibitory concentration in the cell culture medium for the at least one metabolite by regulating enzyme expression to reduce synthesis of the at least one metabolite, wherein: the at least one metabolite is at least one of aconitic acid (AA), leucinic acid (HICA), cytidine monophosphate (CMP), methylsuccinic acid (MSA), trigonelline (TRI), N-acetylputrescinium (NAP), or a combination thereof; the enzyme to reduce the synthesis of HICA comprises at least one of alcohol dehydrogenase 5 (ADH5), branched-chain amino acid transaminase 1 (BCAT1), solute carrier family 35 member A1 (SLC35A1), glutamic oxaloacetic transaminase 1 (GOT1), hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB), or a combination thereof; the enzyme to reduce the synthesis of CMP comprises at least one of ADH5, BCAT1, catalase (CAT), GOT1, 4-hydroxy-2-oxoglutarate aldolase 1 (HOGA1), SLC35A1, HADHB or a combination thereof; the enzyme to reduce the synthesis of MSA comprises at least one of BCAT1, GOT1, HADHB, HOGA1, SLC35A1 or a combination thereof; the enzyme to reduce the synthesis of TRI comprises at least one of BCAT1, GOT1, HADHB, CAT, HOGA1, SLC35A1, or a combination thereof; the enzyme to reduce the synthesis of NAP comprises at least one of BCAT1, SLC35A1, HOGA1, GOT1, CAT, HADHB or a combination thereof; and the enzyme to reduce the synthesis of trans-aconitic acid comprises at least one of BCAT1, ADH5, GOT1, HOGA1, SLC35A1, HADHB, or a combination thereof, wherein the enzyme comprises at ADH5 and BCAT1 (see claim 1 of patent ‘851).
Regarding claims 2-3 and 17-18, patent ‘851 teaches “wherein regulating enzyme expression to reduce the synthesis of the metabolite comprises adding a recombinant DNA molecule to overexpress the regulating enzyme, wherein the regulating enzyme is a downstream enzyme” (see claims 2-3 of patent ‘851).
Regarding claims 15 and 27, patent ‘851 teaches “wherein the concentration of the at least one metabolite is measured using nuclear magnetic resonance (NMR) spectroscopy, Raman spectroscopy, High/Ultra Performance Liquid Chromatography (H/UPLC), Liquid Chromatography Mass Spectrometer (LC-MS), Gas Chromatography Mass Spectrometer (GC- MS) technology, or a combination thereof” (see claim 6 of patent ‘851).
Regarding claims 7 and 20, patent ‘851 teaches “wherein maintaining the at least one metabolite below an inhibitory concentration in the cell culture medium for the at least one metabolite comprises controlling temperature, dissolved oxygen level, pH, or a combination thereof” (see claim 7 of patent ‘851) and “wherein the cell culture is a batch culture, a fed batch culture, or a perfusion culture” (see claim 8 of patent ‘851).
Regarding claims 8 and 21, patent ‘851 teaches “wherein the cells are CHO cells, HEK 293 cells, HT-1080 cells, engineered T cells, or engineered natural killer cells” (see claim 8 of patent ‘851).
Regarding claims 10-11 and 22-23, patent ‘851 teaches “wherein the cells express a recombinant protein, a gene product, or a cell product” and “wherein the recombinant protein is a monoclonal antibody” (see claims 9-10 of patent ‘851).
Regarding claims 12-13 and 24-25, patent ‘851 teaches “wherein cell growth and/or productivity are increased as compared to a control culture, wherein the control culture is identical to the culture of claim 1 except it is not cultured using step (ii)” and “wherein the cell growth is determined by maximum viable cell density and is increased by at least 5% as compared to the control culture” (see claims 11-12 of patent ‘851).
Regarding claims 14 and 26, patent ‘851 teaches “wherein the metabolite is AA and the inhibitory concentration is lower than 100 µM, 440 µM, 880 µM, 3 mM, 5 mM or 10 mM, wherein the metabolite is HICA and the inhibitory concentration is lower than 10 µM, 23.5 µM, 47 µM, 100 µM, 1 mM, or 3 mM, wherein the metabolite is CMP and the inhibitory concentration is 5 µM, 10 µM, 20 µM, 100 µM, 500 µM, or 1 mM, wherein the metabolite is MSA and the inhibitory concentration is lower than 1 µM, 3.75 µM, 7.5 µM, 100 µM, 1 mM or 3 mM, wherein the metabolite is TRI and the inhibitory concentration is lower than 0.1 µM, 0.35 µM, 0.7 µM, 100 µM, 1 mM or 3 mM, or wherein the metabolite is NAP and the inhibitory concentration is lower than 0.1 µM, 0.3 µM, 0.6 µM, 100 µM, 1 mM or 3 mM” (see claim 13 of patent ‘851).
Conclusion
No claims were allowed.
Applicant’s amendment and IDS necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGHI V NGUYEN whose telephone number is (571)270-3055. The examiner can normally be reached Mon-Fri: 9 - 3 pm (EST).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
