Prosecution Insights
Last updated: April 19, 2026
Application No. 18/067,892

CELL CULTURE METHOD

Final Rejection §103
Filed
Dec 19, 2022
Examiner
KIPOUROS, HOLLY MICHAELA
Art Unit
1799
Tech Center
1700 — Chemical & Materials Engineering
Assignee
BAYER AKTIENGESELLSCHAFT
OA Round
2 (Final)
70%
Grant Probability
Favorable
3-4
OA Rounds
3y 1m
To Grant
93%
With Interview

Examiner Intelligence

Grants 70% — above average
70%
Career Allow Rate
356 granted / 509 resolved
+4.9% vs TC avg
Strong +23% interview lift
Without
With
+22.9%
Interview Lift
resolved cases with interview
Typical timeline
3y 1m
Avg Prosecution
37 currently pending
Career history
546
Total Applications
across all art units

Statute-Specific Performance

§101
0.4%
-39.6% vs TC avg
§103
45.9%
+5.9% vs TC avg
§102
21.6%
-18.4% vs TC avg
§112
23.8%
-16.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 509 resolved cases

Office Action

§103
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 . Response to Arguments Applicant’s arguments with respect to claims 1-8 have been considered but are moot in view of a new grounds of rejection necessitated by the amendments to the claims. Claim Objections Claim 8 is objected to because of the following informalities: In claim 8, it is recommended to amend the claim so as to recite “at least a top or a bottom cell culture chamber are insulated” as explicit antecedent basis is not provided for the top or the bottom cell culture chamber. Appropriate correction is required. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. Claims 1-3 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Klaus (US Patent Application Publication 2006/0014274) in view of Nozaki et al. (US Patent Application Publication 2016/0017271). Regarding claim 1, Klaus discloses a method for improving a cell culture (Abstract, para. 76, 160) comprising: heating a cell culture process fluid using a closed-pore (reads on dense as claimed, consistent with Applicant’s specification) membrane hollow fiber module (para. 67, 160) (note: the module reads on being single-use as it is structurally capable of being discarded by a user after a single use), wherein the single-use dense membrane hollow fiber module comprises a plurality of closed-pore (dense) membranes arranged as hollow fibers in a housing (para. 67, 130-131, 160); and wherein the cell culture has at least one cell culture chamber having a bottom and a top (para. 152-160) (Fig. 6, sheet 4 of 11). Klaus discloses wherein at least one cell culture process conducted within the at least one cell culture chamber is conducted at a controlled temperature (para. 160). Klaus is silent as to wherein at least a bottom or at least a top of the cell culture chamber is covered with an insulation. Nozaki et al. discloses covering at least a bottom and at least a top of at least one cell culture chamber with an insulation to maintain a temperature therein (para. 70, 76). It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the method disclosed by Klaus such that at least a bottom and/or at least a top of the at least one cell culture chamber is covered with an insulation, based on the teachings of Nozaki et al., in order to maintain a temperature therein for more controlled cell processing. Regarding claim 2, Klaus discloses wherein the single-use dense membrane hollow fiber module comprises a tube side and a shell side (para. 131-132), and during the heating of the cell culture process fluid using the single-use dense membrane hollow fiber module, a heating fluid is passed through the tube side of the single-use dense membrane hollow fiber module while the cell culture process fluid to be warmed is passed through the shell side of the single-use dense membrane hollow fiber module (para. 152-160). Regarding claim 3, Klaus discloses wherein the cell culture process fluid is a cell culture medium (para. 152-160). Regarding claim 7, Klaus discloses wherein the single-use dense membrane hollow fiber module is a single-use dense silicone hollow fiber module (para. 52). Regarding claim 8, Klaus discloses wherein the cell culture is a stacked cell culture having a top and a bottom cell culture chamber (para. 152-160) (Fig. 6, sheet 4 of 11). Klaus in view of Nozaki et al. teaches the insulation, as set forth above; specifically, Nozaki et al. discloses a stacked cell culture wherein at least a top or bottom cell culture chamber are insulated (para. 70, 76, 85-87) (Figs. 9a-9c, sheets 12-14 of 21). It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method disclosed by Klaus such that at least the top or the bottom cell culture chamber are insulated, based on the teachings of Nozaki et al., to maintain desired temperature conditions in a state in which a plurality of chambers are in a stacked configuration. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Klaus (US Patent Application Publication 2006/0014274) in view of Nozaki et al. (US Patent Application Publication 2016/0017271), as applied to claim 1, above, and in further view of Kauffman (US Patent Application Publication 2025/0058277) (already of record). Regarding claim 4, Klaus discloses wherein the heating is carried out by passing the cell culture process fluid through the single-use dense membrane hollow fiber module (para. 152-160), and further discloses general conditions for the volume of the module, i.e., it is a small device having dimensions on the order of millimeters or centimeters (para. 131) (Figs. 1-6, sheets 1-4 of 11). Klaus does not expressly teach wherein the hold up volume is 0.2 liters. Kauffman discloses that that it was known in the art to use a membrane hollow fiber module having a hold-up volume of up to 1 liter for a bench-scale cellular application using a small sample volume (para. 90). It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the method disclosed by Klaus such that the hold up volume is up to 1 liter, as Kauffman discloses that it was known in the art to use such a hold up volume for a bench-scale cellular application using a small sample volume, and the skilled artisan would have been motivated to use a hold up volume recognized in the art to be appropriate for a small-scale cellular operation. Although the prior art combination does not expressly teach the volume of 0.2 liters, the claim range does overlap and/or lie inside the prior art range, and it has been held that in such cases a prima facie case of obviousness exists (MPEP 2144.05). Therefore, the limitation does not introduce a patentable distinction over the prior art. Claim 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Klaus (US Patent Application Publication 2006/0014274) in view of Nozaki et al. (US Patent Application Publication 2016/0017271), as applied to claim 1, above, and in further view of Yoon et al. (Effect of a microwave warming of cell culture media on cell viability and confluence rate). Regarding claim 5, Klaus discloses wherein the heating warms the cell culture process fluid prior to delivery of the cell culture process fluid for use in cell culture, wherein the fluid is cell culture medium (para. 152-160). Klaus is silent as to wherein the heating warms the cell culture process fluid from between 20-22⁰ C to 35-42⁰ C. Yoon et al. discloses that it is beneficial to pre-heat cell culture medium to 37⁰ C before supplying it to a cell culture application to optimize the activity of the medium for cellular metabolism (p. 2307 col. 2 para. 2, p. 2309 col. 2 last paragraph). Yoon et al. further discloses that it is typical in the art to warm up cell culture medium from a frozen or refrigerated temperature (p. 2307 col. 2 para. 2) and expressly teaches a method of heating cell culture from 0⁰ C to 37⁰ C (p. 2309 col. 2 last paragraph) (Fig. 2, p. 2310). It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the heating disclosed by Klaus so as to warm the cell culture process fluid from 0⁰ C to 37⁰ C (note: this heating would necessarily also warm the fluid from 20-22⁰ C to 37⁰ C as in the claim), as Yoon et al. discloses that it was known in the art to do so in order to bring refrigerated or frozen cell culture medium up to a temperature optimized for cell culture processes, and the skilled artisan would have been motivated to provide cell culture medium at a temperature recognized in the art to be optimal for cell culture processing. Regarding claim 6, Klaus discloses wherein the heating warms the cell culture process fluid prior to delivery of the cell culture process fluid for use in cell culture, wherein the fluid is cell culture medium (para. 152-160). Klaus is silent as to wherein the heating takes place in the range of between 10 sec to 3 min. Yoon et al. discloses that it is beneficial to pre-heat cell culture medium to 37⁰ C before supplying it to a cell culture application to optimize the activity of the medium for cellular metabolism (p. 2307 col. 2 para. 2, p. 2309 col. 2 last paragraph). Yoon et al. further discloses that the time to achieve such heating depends on the heating method and volume of culture medium to be heated and discloses general conditions such as 10 seconds to 1 hour for heating wherein the final temperature increases as heating time increases (p. 2307 col. 2 para. 2-p. 2308 col. 2 para. 1) (Fig. 2, p. 2310). It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art as embodied by Yoon et al. discloses general conditions and further that heating time is a result-effective variable, as set forth above. Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover an optimum or workable range for the heating time in order to arrive at a desired final temperature for a given quantity of cell culture medium. Conclusion Applicant's amendment 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 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 HOLLY KIPOUROS whose telephone number is (571)272-0658. The examiner can normally be reached M-F 8.30-5PM. 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, Michael Marcheschi can be reached at 5712721374. 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. /HOLLY KIPOUROS/Primary Examiner, Art Unit 1799
Read full office action

Prosecution Timeline

Dec 19, 2022
Application Filed
Oct 07, 2025
Non-Final Rejection — §103
Dec 17, 2025
Response Filed
Jan 16, 2026
Final Rejection — §103 (current)

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Prosecution Projections

3-4
Expected OA Rounds
70%
Grant Probability
93%
With Interview (+22.9%)
3y 1m
Median Time to Grant
Moderate
PTA Risk
Based on 509 resolved cases by this examiner. Grant probability derived from career allow rate.

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