DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
The instant application claims benefit to US Application No. 14/127050 (filed 04/10/2014), PCT/US2012/045070 (filed 06/29/2012) and US PRO 61/503737 (filed 07/01/2011) and is acknowledged. The instant claims herein are examined using the effective filing date of 07/01/2011 for the basis of any prior art rejections.
Election/Restrictions
Applicant’s election of Group I, claims 1-7 in the reply filed on 09/19/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 8-16 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/19/2025.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 03/02/2023 was properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) was considered.
The information disclosure statement filed 06/21/2022 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Drawings
The drawings are objected to because the drawings recite “Figure” instead of “FIG.”. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the specification refers to the drawings as “Figure” instead of “FIG.”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites the limitation "the transition" in line 1. There is insufficient antecedent basis for this limitation in the claim as there is no previous recitation of any transition earlier in the claim or in claim 2, from which this claim depends.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
First rejection
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-11, 16-20, and 26-27 of U.S. Patent No. 11827692. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below. The claims of the ‘692 patent are recited below, with the overlapping limitations at issue in bold.
1. A method of culturing Chinese Hamster Ovary (CHO) cells expressing a monoclonal antibody, wherein said monoclonal antibody is denosumab, comprising;
(a) establishing a CHO cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/ml in a serum-free culture medium;
(b) growing the CHO cells during a growth phase and supplementing the culture medium with bolus feeds of a serum-free feed medium;
(c) starting perfusion when viable cell density (VCD) is at least 10×106 viable cells/mL;
(d) maintaining the CHO cells by perfusion with a serum-free perfusion medium, wherein the VCD of the culture is maintained at between 10×106 viable cells/mL and 1×108 cells/mL; and
(e) harvesting the monoclonal antibody produced by the CHO cells.
7. The method of claim 1, wherein in step (d), said perfusion medium comprises L-asparagine at a concentration of 5 mM or less.
8. The method of claim 1, further comprising a temperature shift wherein temperature of the culture is lowered.
9. The method of claim 1, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
10. The method of claim 1, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C., and the production phase occurs at a second temperature that is between 30° C. and 34° C.
11. A method of culturing Chinese Hamster Ovary (CHO) cells expressing a monoclonal antibody, wherein said monoclonal antibody is denosumab, comprising;
(a) establishing a CHO cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/ml in a serum-free culture medium;
(b) growing the CHO cells during a growth phase and supplementing the culture medium with bolus feeds of a serum-free feed medium;
(c) starting perfusion between day 5 and day 9 of the cell culture;
(d) maintaining the CHO cells by perfusion with a serum-free perfusion medium, wherein the VCD of the culture is maintained at between 10×106 viable cells/mL and 80×106 cells/mL; and
(e) harvesting the monoclonal antibody produced by the CHO cells.
16. The method of claim 11, wherein in step (d), said perfusion medium comprises L-asparagine at a concentration of 5 mM or less.
17. The method of claim 11, further comprising a temperature shift wherein temperature of the culture is lowered.
18. The method of claim 11, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
19. The method of claim 11, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C., and the production phase occurs at a second temperature that is between 30° C. and 34° C.
20. A method of culturing Chinese Hamster Ovary (CHO) cells expressing a monoclonal antibody, wherein said monoclonal antibody is denosumab, comprising;
(a) establishing a CHO cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/ml in a serum-free culture medium;
(b) growing the CHO cells during a growth phase and supplementing the culture medium with bolus feeds of a serum-free feed medium;
(c) starting perfusion when viable cell density (VCD) is at least 10×106 viable cells/mL;
(d) maintaining the CHO cells by perfusion with a serum-free perfusion medium, wherein the packed cell volume (PCV) of the culture is maintained at between 10% to 35%; and
(e) harvesting the monoclonal antibody produced by the CHO cells.
26. The method of claim 20, wherein in step (d), said perfusion medium comprises L-asparagine at a concentration of 5 mM or less.
27. The method of claim 1, further comprising a temperature shift wherein temperature of the culture is lowered.
As it relates to the instantly claimed invention, it is clear that the patent claims are an obvious variant of the instantly claimed invention.
This is a nonstatutory double patenting rejection.
Second rejection
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 9, 11, 14-16, 19, 23, 26-28, 30 of U.S. Patent No. 11685772. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below. The claims of the patent are recited below, with the overlapping limitations at issue in bold.
1. A method of producing a monoclonal antibody, comprising:
establishing a Chinese Hamster Ovary (CHO) cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL, wherein said CHO cell expresses said monoclonal antibody,
limiting the viable cell density (VCD) of said culture at 1×108 cells/mL by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less,
maintaining the CHO cells by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, such that the VCD of the culture is maintained at 1×108 cells/mL or less.
4. The method of claim 1, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
5. The method of claim 4, wherein the temperature shift occurs at the transition between a growth phase and a production phase.
6. The method of claim 4, wherein the temperature shift occurs during a production phase.
9. The method of claim 1, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C., and the production phase occurs at a second temperature that is between 30° C. and 34° C.
11. A method of producing denosumab, comprising:
establishing a Chinese Hamster Ovary (CHO) cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL, wherein said CHO cell expresses denosumab,
limiting the viable cell density (VCD) of said culture at 1×108 cells/mL by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less,
maintaining the CHO cells by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, such that the VCD of the culture is maintained at 1×108 cells/mL or less.
14. The method of claim 11, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
15. The method of claim 14, wherein the temperature shift occurs at the transition between a growth phase and a production phase.
16. The method of claim 14, wherein the temperature shift occurs during a production phase.
19. The method of claim 11, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C., and the production phase occurs at a second temperature that is between 30° C. and 34° C.
23. A method of producing panitumumab, comprising:
establishing a Chinese Hamster Ovary (CHO) cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL, wherein said CHO cell expresses panitumumab,
limiting the viable cell density (VCD) of said culture at 1×108 cells/mL by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less,
maintaining the CHO cells by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, such that the VCD of the culture is maintained at 1×108 cells/mL or less.
26. The method of claim 23, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
27. The method of claim 26, wherein the temperature shift occurs at the transition between a growth phase and a production phase.
28. The method of claim 26, wherein the temperature shift occurs during a production phase.
30. The method of claim 23, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C., and the production phase occurs at a second temperature that is between 30° C. and 34° C.
As it relates to the instantly claimed invention, it is clear that the patent claims are an obvious variant of the instantly claimed invention.
This is a nonstatutory double patenting rejection.
Third rejection
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 10-18, 20, 26, and 30-35 of U.S. Patent No. 11673941. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below. The claims of the patent are recited below, with the overlapping limitations at issue in bold.
1. A method of culturing mammalian cells expressing a recombinant protein comprising;
(a) establishing a mammalian cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/ml in a serum-free culture medium;
(b) growing the mammalian cells during a growth phase and supplementing the culture medium with bolus feeds of a serum-free feed medium,
(c) starting perfusion when viable cell density (VCD) is at least 10×106 viable cells/mL, and
(d) maintaining the mammalian cells by perfusion with a serum-free perfusion medium, wherein the packed cell volume during the production phase is less than or equal to 35%.
7. The method according to claim 1, wherein in step (d), said perfusion medium comprises having an L asparagine at a concentration of 5 mM or less.
10. The method according to claim 1, wherein the packed cell volume is less than or equal to 30%.
11. The method of claim 1, wherein the packed cell volume is at between 10% and 35%.
12. The method of claim 1, wherein the packed cell volume is at between 20% and 35%.
13. The method according to claim 1, further comprising a temperature shift wherein temperature of the culture is lowered.
14. The method according to claim 13, wherein the temperature shift occurs at the transition between the growth phase and production phase.
15. The method according to claim 1, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C. and the production phase occurs at a second temperature that is between 30° C. and 34° C.
16. The method according to claim 1, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
17. The method according to claim 1, further comprising a temperature shift from 36° C. to 31° C.
18. The method according to claim 1, further comprising a temperature shift from 36° C. to 33° C.
20. A method of culturing mammalian cells expressing a recombinant protein comprising;
(a) establishing a mammalian cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/ml in a serum-free culture medium;
(b) growing the mammalian cells during a growth phase and supplementing the culture medium with bolus feeds of a serum-free feed medium,
(c) starting perfusion when viable cell density (VCD) is at least 10×106 viable cells/mL, and
(d) maintaining the mammalian cells by perfusion with a serum-free perfusion medium, wherein the VCD of the culture is maintained at 1×108 cells/mL or less.
26. The method of claim 20, wherein in step (d) said perfusion medium comprises L asparagine at a concentration of 5 mM or less.
30. The method of claim 20, further comprising a temperature shift wherein temperature of the culture is lowered.
31. The method of claim 30, wherein the temperature shift occurs at the transition between the growth phase and production phase.
32. The method of claim 20, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C., and the production phase occurs at a second temperature that is between 30° C. and 34° C.
33. The method of claim 20, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
34. The method of claim 20, further comprising a temperature shift from 36° C. to 31° C.
35. The method of claim 20, further comprising a temperature shift from 36° C. to 33° C.
As it relates to the instantly claimed invention, it is clear that the patent claims are an obvious variant of the instantly claimed invention.
This is a nonstatutory double patenting rejection.
Fourth rejection
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-12, 14-22, 24, 30-34, and 38-41 of U.S. Patent No. 11634476. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below. The claims of the patent are recited below, with the overlapping limitations at issue in bold.
1. A method of limiting a mammalian cell culture at a packed cell volume (PCV) of 35% or less, wherein said mammalian cell expresses a recombinant protein, comprising:
establishing a mammalian cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL,
limiting the PCV of said culture by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less,
maintaining the mammalian cells by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, and
monitoring the cell culture, such that the PCV of the culture is maintained at 35% or less.
8. The method of claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 4.0 mM.
9. The method of claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 3.0 mM.
10. The method of claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 2.0 mM.
11. The method of claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 1.0 mM.
12. The method of claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is equal to 0 mM.
14. The method of claim 1, wherein the PCV is maintained at 30% or less.
15. The method of claim 1, wherein the PCV is maintained at between 10% and 35%.
16. The method of claim 1, wherein the PCV is maintained at between 20% and 35%.
17. The method according to claim 1, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
18. The method according to claim 17, wherein the temperature shift occurs at the transition between a growth phase and a production phase.
19. The method according to claim 17, wherein the temperature shift occurs during a production phase.
20. The method of claim 1, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C. and the production phase occurs at a second temperature that is between 30° C. and 34° C.
21. The method according to claim 1, further comprising a temperature shift from 36° C. to 31° C.
22. The method according to claim 1, further comprising a temperature shift from 36° C. to 33° C.
24. A method of limiting a mammalian cell culture at a viable cell density (VCD) of 1×108 cells/mL or less, wherein said mammalian cell expresses a recombinant protein, comprising:
establishing a mammalian cell culture in a serum-free culture medium in a bioreactor by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL,
limiting the VCD of said culture by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less,
maintaining the mammalian cells by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, and
monitoring the cell culture, such that the VCD of the culture is maintained at 1×108 cells/mL or less.
30. The method of claim 24, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 4.0 mM.
31. The method of claim 24, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 3.0 mM.
32. The method of claim 24, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 2.0 mM.
33. The method of claim 24, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 1.0 mM.
34. The method of claim 24, wherein the concentration of L-asparagine in the serum-free perfusion medium is equal to 0 mM.
38. The method of claim 24, further comprising a temperature shift, wherein the temperature is lowered from between 35° C. and 38° C. to between 30° C. and 34° C.
39. The method of claim 38, wherein the temperature shift occurs at the transition between a growth phase and a production phase.
40. The method of claim 38, wherein the temperature shift occurs during a production phase.
41. The method of claim 24, further comprising a temperature shift, wherein the growth phase occurs at a first temperature that is between 35° C. and 38° C. and the production phase occurs at a second temperature that is between 30° C. and 34° C.
As it relates to the instantly claimed invention, it is clear that the patent claims are an obvious variant of the instantly claimed invention.
This is a nonstatutory double patenting rejection.
Fifth rejection
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-7, 9-10, 14-19, 24-28, and 39 of U.S. Patent No. 11292829. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below. The claims of the patent are recited below, with the overlapping limitations at issue in bold.
1. A method of inducing growth arrest in a mammalian cell culture such that cells stop increasing in number, as measured by viable cell density (VCD), wherein the mammalian cells are Chinese Hamster Ovary (CHO) cells, comprising:
establishing a mammalian cell culture in a serum-free culture medium in a bioreactor, wherein the mammalian cell culture is established by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL;
perfusing said culture with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less;
maintaining the mammalian cells in by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, such that the cells stop increasing in number before viable cell density exceeds 1×108 cells/mL.
5. The method according to claim 2, wherein the maximum VCD of said culture is further limited by a temperature shift from a first temperature to a second temperature, wherein the first temperature is between 35° C. and 38° C., and the second temperature is between 30° C. and 34° C.
6. The method according to claim 5, wherein the temperature shift occurs at the transition between the growth phase and production phase.
7. The method according to claim 5, wherein the temperature shift occurs during the production phase.
9. The method according to claim 2, wherein the packed cell volume, as measured by the ratio of the volume occupied by the cells to the total volume of cell culture, during the production phase is less than or equal to 35%.
10. The method according to claim 2, wherein the packed cell volume during the production phase is less than or equal to 30%.
14. The method according to claim 1, further comprising a temperature shift from 36° C. to 31° C.
15. The method according to claim 14, wherein the temperature shift occurs at the transition between a growth phase and a production phase.
16. The method according to claim 14, wherein the temperature shift occurs during a production phase.
17. The method according to claim 1, further comprising a temperature shift from 36° C. to 33° C.
19. The method according to claim 1, wherein the maximum VCD of said culture is further limited by a temperature shift from a first temperature to a second temperature, wherein the first temperature is between 35° C. and 38° C., and the second temperature is between 30° C. and 34° C.
24. The method according to claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 4.0 mM.
25. The method according to claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 3.0 mM.
26. The method according claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 2.0 mM.
27. The method according to claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is less than or equal to 1.0 mM.
28. The method according to claim 1, wherein the concentration of L-asparagine in the serum-free perfusion medium is 0 mM.
39. A method of inducing growth arrest of a mammalian cell culture in a bioreactor, such that cells stop increasing in number, as measured by viable cell density (VCD), wherein the mammalian cells are Chinese Hamster Ovary (CHO) cells, comprising:
establishing a CHO cell culture in a serum-free culture medium in a bioreactor, wherein the mammalian cell culture is established by inoculating the bioreactor with at least 0.5×106 to 3.0×106 cells/mL;
perfusing said culture with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less;
maintaining the mammalian cells in by perfusion with a serum-free perfusion medium having an L-asparagine concentration of 5 mM or less, such that the packed cell volume does not exceed 35%.
As it relates to the instantly claimed invention, it is clear that the patent claims are an obvious variant of the instantly claimed invention.
This is a nonstatutory double patenting rejection.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Bebbington, C., Renner, G., Thomson, S. et al. High-Level Expression of a Recombinant Antibody from Myeloma Cells Using a Glutamine Synthetase Gene as an Amplifiable Selectable Marker. Nat Biotechnol 10, 169–175 (1992): discusses introducing a glutamine synthetase (GS) selectable marker into myeloma cells in which transfectants are selected by growth in a glutamine-free medium. Vector amplification can subsequently be selected using the specific inhibitor of GS, methionine sulphoximine (MSX). The reference teaches that supplementation with 500 uM rescues cells in DMEM and supports growth of the cells transfected with the pCMGS recombinant vector (see abstract, throughout).
Li P, Yin Y-L, Li D, Woo Kim S, Wu G. Amino acids and immune function. British Journal of Nutrition. 2007;98(2):237-252: discusses amino acids and immune function. Li explicitly teaches asparagine (2mM) prevented apoptosis and increased cell growth in lymphocytes (see pg. 242, col 1).
Altamirano et al. Specific nutrient supplementation of defined serum-free medium for the improvement of CHO cells growth and t-PA production. Electron. J. Biotechnol.. 2006. Vol. 9(1):61-68: discusses “[r]ecombinant CHO TF70R cells are able to grow and produce t-PA on serum-free medium BIOPRO1 (BioWhitaker Europe, Belgium). The purpose of the study was to determine the effect of medium supplementation with vitamins, lipids, and specific amino acids on cell growth, t-PA production and biological functionality. Among vitamins, only biotin, folic acid, cobalamine and benzoic acid were required for improving growth and t-PA production. Lipid supplement allowed a significant increase cell concentration and t-PA specific activity and concentration, though its specific production rate decreased slightly. Medium supplementation with proline, serine and asparagine had also positive effects on cell growth. Besides, the addition of asparagine (even in the presence of glutamine) was essential for the production and biological quality of the t-PA” (see abstract, throughout document).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672