Office Action 2: Notice of Allowance (2025-01-06)

CLAIMS:
AMENDMENTS TO CLAIMS:

This listing of claims will replace all prior versions and listings of claims in the instant application.

1\. (Previously Presented) A method for culturing cells comprising:(a) culturing cells in a first seed train culture to a viable cell concentration of greater than 3.0 x 106 cells/mL, whereby a metabolic shift to lactate consumption has occurred in the first seed train culture;
(b) transferring an amount of cells from the first seed train culture to a second seed train culture in another culture vessel;
(c) culturing the cells in the second seed train culture; and
(d) transferring an amount of cells from the second seed train culture to a production culture after the cells in the second seed train culture have reached a predetermined viable cell concentration greater than 3.0 x 106 cells/mL.

2\. (Canceled)

3\. (Previously Presented) The method of Claim 1, wherein the cells in said first seed train culture are cultured to a viable cell concentration of 3.5 x 106 cells/mL to 5.0 x 106 cells/mL.

4\. (Previously Presented) The method of Claim 3, wherein the cells in said first seed train culture are cultured to a viable cell concentration of 4.0 x 106 cells/mL, 4.5 x 106 cells/mL or 5.0 x 106 cells/mL.

5\. (Currently Amended) The method of Claim 1, wherein the cells in said first seed train culture are cultured to a viable cell concentration of at least 4.5 x 106 cells/mL.

6\. (Canceled)

7\. (Previously Presented) The method of Claim 1, wherein said predetermined viable cell concentration is 3.5 x 106 cells/mL to 5.0 x 106 cells/mL.

8\. (Original) The method of Claim 7, wherein said predetermined viable cell concentration is 3.5 x 106 cells/mL, 4.0 x 106 cells/mL, 4.5 x 106 cells/mL or 5.0 x 106 cells/mL.

9\. (Canceled)

10\. (Canceled)

11\. (Canceled)

12\. (Currently Amended) The method of Claim 1, further comprising detecting a rate of lactate accumulation in the second seed train culture prior to transfer to the production culture, wherein the rate of lactate accumulation is reduced compared to that determined in an otherwise identical cell culture under otherwise identical conditions except that cells are transferred from the first seed train culture to the second seed train culture rior to a metabolic shift- or rior to the viable cell count reaching 3.0 x 106 cells/mL.

13\. (Canceled)

14\. (Previously Presented) The method of Claim 1, wherein said metabolic shift to lactate consumption is detected by pH, lactate or base measurement in said first seed train culture.

15\. (Previously Presented) The method of Claim 14, wherein said metabolic shift to lactate consumption is detected after pH increases in said first seed train culture medium without addition of base.

16\. (Previously Presented) The method of Claim 14, wherein said metabolic shift occurs when lactate levels plateau in said first seed train culture.

17\. (Currently Amended) The method of Claim 1, wherein the metabolic shift occurs when said cells emerge from log growth phase or have reached stationary phase in said first seed train culture.

18\. (Currently Amended) The method of Claim 1, wherein the cells in said first seed train culture are transfected with DNA encoding a polypeptide of interest prior to culturing cells in a first seed train culture.

19\. (Previously Presented) The method of Claim 18, further comprising maintaining said second seed train culture and said production culture under conditions that allow expression of said polypeptide of interest, and harvesting said polypeptide of interest from said production culture.

20\. (Original) The method of Claim 19, wherein said protein of interest is selected from the group consisting of antibody, antigen-binding protein, and fusion protein.

21\. (Previously Presented) A production culture produced by the method of Claim 1.

22.-29. (Canceled)2328

OFFICE 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 .
Reasons for allowance
Claims 1,3-5,7-8,12 and 14-21 are allowed.
Applicant’s claim amendments, arguments and terminal disclaimer, filed 10/17/2024, have overcome the 35 USC 112 (b) and nonstatutory time double patenting rejections.
The closest prior art of record is Heidemann, US 2003/0113915, (of record), which teaches a method for seed-train expansion of cryopreserved cells by using an inoculation bioreactor having an inoculation well for expanding the cells prior to their transfer to a production bioreactor, and monitoring and adjusting the condition of the media and environment, and thereafter incrementally increasing the volume of the media within the reactor so that optimal cell growth is maintained (e.g. Abstract, [0010]).
However, Heidemann does not teach and does not fairly suggest the recited viable cell concentration (VCC) of either the first seed train culture or after the second seed train culture reaches the claimed VCC range prior to passaging of the cells.
Conclusion

APPLICANT REBUTTAL: REMARKS
In the Office Action dated June 18, 2024, claims 1, 3-5, 7-8, 12 and 14-21 were pending and under consideration. Claims 5 and 12 were rejected under 35 U.S.C. § 112(b) as allegedly indefinite. Claims 1, 3-5, 7-8, 12 and 14-21 were rejected on the ground of nonstatutory double patenting as allegedly unpatentable over claims 1-15 of U.S. Patent No. 11,390,663 B2 ('663).
This Response address each rejection raised in the Office Action. Favorable consideration is respectfully requested.
35 U
.
S.C.
12(b)
Claims 5 and 12 are rejected under 35 U.S.C. § 112(b) as allegedly indefinite.
Regarding claim 5, the phrase "said first cell culture" in line 1 of the claim is said to be vague, because claim 5 depends from claim 1, which recites "a first seed train culture".
Applicant has amended claim 5 to refer to "said first seed train culture", which is believed to obviate the rejection.
Regarding claim 12, the Examiner considers the recitation "compared to that
determined in an otherwise identical cell culture under otherwise identical conditions except transferring cells to the second seed train culture is performed prior to a metabolic shift, or is performed prior to the viable cell count reaching 3.0 x 106 cells/ml" in lines 3-6 to be vague.
Without acquiescing to the rejection, Applicant has amended claim 12 for improved clarity. Based on the language in claim 12 as presently recited, it is clear that the rate of lactate accumulation in the second culture is reduced as compared to the scenario where the cells are transferred to the second culture prior to the metabolic shift or prior to the VCC reaching the recited value. Applicant respectfully submits that claim 12 as amended is not indefinite.
Accordingly, the rejections of claims 5 and 12 under 35 U.S.C. § 112(b) are overcome and withdrawal thereof is respectfully requested.
Nonstatuto
ry
Double Patentin
g
Claims 1, 3-5, 7-8, 12 and 14-21 are rejected on the ground of nonstatutory double patenting as allegedly unpatentable over claims 1-15 of U.S. Patent No. 11,390,663 B2.
Without acquiescing to the rejection, Applicant respectfully submits herewith a terminal disclaimer over U.S. Patent No. 11,390,663 B2. Thus, the rejection is moot and withdrawal thereof is respectfully requested. It is respectfully submitted that "filing of a terminal disclaimer simply serves the statutory function of removing the rejection of double patenting, and raises neither a presumption nor estoppel on the merits of the rejection."
O
uad Environmental Technolo
gi
es Co
rp
. v. Union Sanitary District,
946 F.2d 870 (Fed. Cir. 1991).
Conclusion


CITED REFERENCE SUMMARIES: Ref US20030113915: Claims:
1. A method of mammalian cell seed-train expansion comprising: 
a) providing a bioreactor having an inoculation well,  b) delivering a suspension of mammalian cells to media within the inoculation well,  c) controlling environmental conditions and composition of said media so that cell growth within the inoculation well is optimized,  d) growing the mammalian cells until a predetermined cell density is reached within said well, and  e) increasing the media volume incrementally while maintain optimum environmental conditions and environmental growth conditions until the bioreactor is filled to a predetermined volume and cell density.
2. The method of claim 1, wherein the mammalian cells are cryopreserved cells.
3. The method of claim 1, wherein the mammalian cells are selected from the group consisting of chinese hamster ovary cells and baby hamster kidney cells.
4. The method of claim 1, wherein the cells are obtained from a cryobag.
5. The method of claim 1, wherein the cells are obtained from a cryovial.
6. An improved fermentation bioreactor comprising: 
a) a bioreactor, said bioreactor defining a chamber,  b) said chamber having exterior and interior sides, a top member, wall member, and base member, said base member having an orifice,  c) an inoculation well, said well defining a chamber having exterior and interior sides, top and base members, a wall member, and  d) said well further including an orifice in said top member joined to said bioreactor orifice, so that a channel is formed between the well chamber and the bioreactor chamber to permit unrestricted movement there between.
7. An improved bioreactor as recited in claim 6, in which the inoculation well chamber is provided with sensors selected from the group consisting of: pH sensor, oxygen sensor, temperature sensor, and optical sensor.
8. An improved bioreactor as recited in claim 6, in which the inoculation well is provided with a communication orifice through the wall of said well to permit the introduction of media and agents into the well chamber.
9. An improved bioreactor as recited in claim 6, in which the inoculation well is provided with a mechanical arm to permit stirring of the contents of said well.