DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 06/23/2026 in response to the Non-Final Rejection mailed on 03/30/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-6 and 12-22 are pending.
4. Applicant’s remarks filed on 06/23/2026 in response to the Non-Final Rejection mailed on 03/30/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Rejections - 35 USC § 112(b)
5. The rejection of claims 1-6 and 12-22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for indefiniteness is withdrawn in view of applicants’ amendment to the claims to remove the recitation “or an amino group”.
Claim Rejections - 35 USC § 103
6. The rejection of claims 1-6 and 12-22 under 35 U.S.C. 103 as being unpatentable over Nakai et al. (WO 2018/159847 A2, published 09/07/2018; cited on IDS filed 09/09/2022 with US Patent Application Publication 2019/0322975 A1 serving as English translation; cited on IDS filed 09/09/2022) in view of Jemaa et al. (US Patent Application Publication 2016/0312317 A1; cited on IDS filed on 09/09/2022), Othman et al. (Frontiers in Microbiology, 2017; cited on PTO-892 mailed on 04/30/2025), Zakhodyaeva et al. (Theoretical Foundations of Chemical Engineering, 2011; cited on PTO-892 mailed on 04/30/2025), and Chung et al. (WO 03/028485 A1; cited on PTO-892 mailed on 03/30/2026), and evidenced by DIAION WA30 (Mitsubishi Chemical Corp., p. 1-2) is maintained for the reasons of record and the reasons set forth below.
7. With respect to claim 1, Nakai et al. a cell culture method comprising: providing a cell culture apparatus and a first and second filter membrane such as an ultrafiltration membrane that separates the culture solution and a metabolic decomposition product removal step of bringing a culture solution containing a metabolic decomposition product into contact with a polymer and removing the metabolic decomposition product from the culture solution to a purified culture solution; and a cell culture step of culturing cells using the purified culture solution [see Abstract; see paragraphs 0070-0079].
With respect to claim 2, Nakai et al. teach the method wherein the culture solution containing the metabolic decomposition product is a culture solution taken out from the culture solution in the culture step [see paragraphs 0070-0079].
With respect to claim 3, Nakai et al. teach the method wherein the culture solution containing the metabolic decomposition product does not contain cells [see paragraphs 0070-0079 and Figure 1].
With respect to claim 4, Nakai et al. teach the method wherein the metabolic decomposition product removal step is a step of passing the filtered culture solution through a purification unit filled with the polymer and removing the metabolic decomposition product from the culture solution to obtain the purified culture solution, the culture step is a step of culturing cells using the purified culture solution in a culture vessel, an inlet side of the purification unit and the culture vessel are connected by a flow channel having a separation membrane in the middle of the flow channel, and the filtered culture solution is a culture solution obtained by filtering, with the separation membrane, the culture solution taken out from the culture solution in the culture step through the flow channel [see Figure 1; paragraphs 0070-0079].
With respect to claims 5 and 6, Nakai et al. teach the method of adding a nutritional component to the purified culture solution, wherein the nutritional component is energy sources and growth supporting factors [see paragraphs 0008]. Given the breadth of the terms “energy sources” and “growth supporting factors”, it is the examiners position that the culture medium containing nutrient components as taught by Nakai et al. would inherently contain these components, given that it is known by one of ordinary skill in the art that these components are necessary for cell culturing.
With respect to claims 14-19, Nakai et al. teach the method wherein the cell is a floating, animal cell such as CHO cell that produces an antibody [see paragraphs 0007-0010; 0053; 0070-0079].
With respect to claim 20, Nakai et al. a cell culture method comprising: a metabolic decomposition product removal step of bringing a culture solution containing a metabolic decomposition product into contact with a polymer and removing the metabolic decomposition product from the culture solution to a purified culture solution; and a cell culture step of culturing CHO cells using the purified culture solution [see Abstract; see 0007-0010; 0053; paragraphs 0070-0079].
With respect to claim 21, Nakai et al. teach the method wherein the separation membrane capable of separating cell is a ultrafiltration membrane [see Abstract; see paragraphs 0070-0079].
However, Nakai et al. does not teach the method of claim 1, wherein the polymer has a quaternary ammonium base group or an amino group, wherein the metabolic decomposition product is at least one organic acid selected from isovaleric acid, butyric acid, and citric acid and the specific quaternary ammonium structures set forth in claims 1 and 12-13; the method of claim 20, wherein the polymer has a quaternary ammonium base group or an amino group and removing an organic acid selected from the group consisting of isovaleric acid, butyric acid, and citric acid; and the method of claim 22, wherein the metabolic decomposition product is at least one organic acid selected from isovaleric acid and citric acid.
Jemaa et al. teach the efficient separation of acids such as sulfuric acid and lactic acid from acid hydrolysis of biomass to provide sugars for downstream fermentation into biofuels using quaternary ammonium resin that allows for 98.5% recovery of the acid that allows for recycle of the acid [see Abstract; paragraphs 0002, 0017-0021].
Othman et al. teach that lactic acid bacteria are industrially important microorganisms that are recognized for their fermentative ability for the production of lactic acid for various applications; however, lactic acid fermentation often suffers from end product inhibition which decreases the cell growth rate [see Abstract]. Othman et al. teach that the restriction imposed by lactic acid on its fermentation can be avoided by extractive fermentation using quaternary ammonium base resins to absorb lactic acid via acid-base interaction [see p. 4-5].
Zakhodyaeva et al. teach that many foodstuffs and beverages are fermentation products and contain a wide variety of organic acids, whose recovery, separation and determination is an important technological and analytical problem [see p. 739, column 1]. Zakhodyaeva et al. teach that quaternary ammonium base and amines are effective in extracting organic acids such as butyric acids [see Abstract; p. 741; Tables 2 and 3].
Chung et al. teach processes for deacidifying juice by removing citric acid from said juice using ion-exchange columns loaded with polystyrene based quaternary ammonium resin such as Amberlite IRA-67, Amberlite IRA-95, Dowex 67, Dowex 77 and Diaion WA 30 [see Abstract; paragraphs 0013-0015; 0022-0025]. Polystyrene contains the general formular of (P1) and evidentiary reference Diaion WA 30 demonstrate the primary functional group is a tertiary amine.
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Nakai et al., Jemaa et al., Othman et al., Zakhodyaeva et al., and Chung et al. according to the teachings of Jemaa et al., Othman et al., Zakhodyaeva et al. and Chung et al. to include a quaternary ammonium resin in the separation unit of Nakai et al. because Nakai et al. teach a cell culture method comprising: a metabolic decomposition product removal step of bringing a culture solution containing a metabolic decomposition product into contact with a polymer and removing the metabolic decomposition product from the culture solution to a purified culture solution; and a cell culture step of culturing cells using the purified culture solution. Both Jemaa et al. and Othman et al. teach the inhibition on cell culture growth in the downstream fermentation processes by organic acids such as lactic acid and teach that quaternary ammonium base resins offer an efficient way to remove said acids from downstream fermentation processes and recycling. Zakhodyaeva et al. teach that quaternary ammonium base and amines are effective in extracting organic acids such as butyric acids useful for food and pharmaceuticals. Chung et al. acknowledges the benefit of polystyrene based quaternary ammonium compound resins in the removal of organic acids from substances. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would have been motivated to combine the teachings of Nakai et al., Jemaa et al., Othman et al., and Zakhodyaeva et al. because both Jemaa et al. and Othman et al. acknowledge that quaternary ammonium base resins offer an efficient way to remove acids from downstream fermentation processes and recycling, and both Zakhodyaeva et al. and Chung et al. acknowledge that quaternary ammonium base and amines are effective in extracting organic acids useful for food and pharmaceuticals. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Remarks Regarding Prior Art Rejections
8. Beginning on p. 9 of applicants’ remarks, applicants in summary contend that Nakai does not disclose or suggest bringing the culture solution into contact with a polymer-packed purification unit for chemical removal of a metabolic decomposition product and the secondary references do not cure this deficiency. Applicants contend that ion-exchange or amine-containing polymeric materials raise biocompatibility concerns and may interact not only with the target acidic components but also other components in a biological medium.
These arguments are found to be not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Furthermore, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). As stated in the rejection above, One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would have been motivated to combine the teachings of Nakai et al., Jemaa et al., Othman et al., and Zakhodyaeva et al. because both Jemaa et al. and Othman et al. acknowledge that quaternary ammonium base resins offer an efficient way to remove acids from downstream fermentation processes and recycling, and both Zakhodyaeva et al. and Chung et al. acknowledge that quaternary ammonium base and amines are effective in extracting organic acids useful for food and pharmaceuticals. Additionally, the use of ion exchange resins containing quaternary ammonium base resins for in situ removal of compounds was already known in the art as reviewed by Othman et al. While it is acknowledged that Othman et al. states that “biocompatibility of resin with microorganism is another important characteristic for resin to possess in order to be used as a lactic acid absorbent”, Othman et al. follows that statement with “[m]ost anion resins show no toxic characteristic to microorganisms, thereby they can be applied directly in bioreactor. In addition, the affinity of cells toward ion exchange resins could be easily understood due to the known chemical composition of the microorganisms’ cell wall…” [see p. 5 of Othman et al.].
Conclusion
9. Status of the claims:
Claims 1-6 and 12-22 are pending.
Claims 1-6 and 12-22 are rejected.
No claims are in condition for an allowance.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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