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 .
Detailed Action
Status of the Claims
Claims 1 and 4-13 are pending.
Claims 14-17 are newly canceled,
Claims 1, 5, 6, and 9 are newly amended,
Claims 1 and 4-13 have been examined on the merits.
Withdrawn Objections & Rejections
Applicant's response filed 10/08/2025 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 05/09/2025 are hereby withdrawn.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 6, 8, and 9-11 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kwak et al (Molecules and Cells (2015)38:3;229-235).
This is a new rejection due to the claim amendments filed 10/08/2025.
Regarding claims 1, 4 and 6: The instant claim 1 recites the term “rescuing”. The instant specification is silent on an explicit definition of the term. The instant specification does recite “It is understood and herein contemplated that to rescue a cell or cell line for culture induced senescence, the cell or cell line must already have become senescent or showing indication of becoming senescent” (p13 ln 17-21), however a contemplation of an embodiment is not considered a special definition as there is not an express intent to clearly redefine the plain meaning of the term “rescue”. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Oxford Languages defines “rescue” as “an act of saving or being saved from danger or distress”. Therefore, in the instant claim, “rescuing a cell from cell culture induced senescence” is interpreted as “saving a cell from cell culture induced senescence” and thus the broadest reasonable interpretation of the term rescuing encompasses both treatment of senescence and prevention of senescence.
The instant claim recites the following active steps: placing a senescent cell or cell line in media comprising an NAD+ precursor or adding a NAD+ precursor to the culture media.
Kwak teach the NAD+ precursor nicotinamide (NAM) has an anti-senescent effect on cells and reduces senescence phenotypes in cells undergoing senescence progression and those already in senescence (abstract).
Kwak teach senescent human fibroblasts that are incubated with NAM show reduced senescent phenotype (reduced SA beta-Gal activity and decreased size) (Fig 4). This reads on adding a NAD+ precursor to the culture media as required by the instant claim.
Regarding claim 8: The teachings of Kwak are discussed supra. Kwak also teach cells are treated with MAN at passage 19 and 36.5 (Fig 4). This reads on the precursor is added to the culture after passage 1 of the instant claim.
Regarding claims 9-11: The teachings of Kwak are discussed supra. Kwak also teach cells are treated for 1 day (Fig 4). This reads on the precursor is added to the culture at least one time every 24 hours and at least 1 time per week as required by the instant claims. This also reads on the precursor is added at least 1 time per passage.
Thus, the teachings of Kwak anticipate the invention as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al (Molecules and Cells (2015)38:3;229-235) as applied to claims 1, 4, 6, 8, and 9-11 above, and further in view of Cho et al (US 2015/0072416, cited previously).
This is a new rejection due to the claim amendments filed 10/08/2025 but also relies on previously cited references.
Regarding claims 5 and 7-8: The teachings of Kwak are discussed supra. The disclosure of Kwak is drawn to the culture of human fibroblast cells. Kwak do not teach the cells comprise stem cells.
Cho teach the culture of H9 human embryonic stem cells in unconditioned medium, and cells treated with NAD+ precursors including nicotinamide (NAM) and NAD+ (p8/9 para 101). Cho further teach that H9 human embryonic stem cells are cultured with unconditioned medium (UM), which comprises DMEM and does not comprise non-human animal components (and thus reads on xeno-free culture medium) (p 10 para 0119).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Kwak drawn to rescuing a cell culture from senescence by using a stem cell culture as taught by Cho.
One of ordinary skill in the art would have been motivated to modify the method as taught by Kwak for the purposes of cultivating stem cells as taught by Cho because Cho teach nicotinamide inhibits the induction of senescence and oxidative stress and increases cell proliferation to improve culture conditions (p3 ¶0017).
One would have had a reasonable expectation of success because Cho discloses beneficial effects of nicotinamide treatment for stem cell culture.
Thus, the teachings of Kwak and Cho renders obvious the invention as claimed.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al (Molecules and Cells (2015)38:3;229-235) as applied to claims 1, 4, 6, 8, and 9-11 above, and further in view of ThermoFisher (ThermoFisher Datasheet (2014), retrieved from the internet May 5 2025 https://www.thermofisher.com/content/dam/LifeTech/migration/files/technical-reference-library/protocols/Protocol_CulturinghMSCsUnderSerumFreeAndXenoFreeConditions_FINAL.pdf, cited previously).
This is a new rejection due to the claim amendments filed 10/08/2025, however relies on previously cited references.
Regarding claim 12: The teachings of Kwak are described above.
Kwak does not teach cells are passaged at least once every 12-168 hours.
ThermoFisher protocol for culturing human mesenchymal stem cells (MSCs) under serum-free and xeno-free conditions teaches a passage schedule for three different media types (p 2/3 Table 1 “passage schedule”). The passage schedule taught by ThermoFisher ranges from 3-7 days (72-168h).
It would have been obvious for one who is skilled in the art to modify the cell culture method of Kwak with the teaching of ThermoFisher. Furthermore, one skilled in the art would understand that cell passage frequency depends on the specific conditions of a cell culture (cell density, cell type, media type etc.) and would use the teaching of ThermoFisher as a starting point to conduct routine optimization of the cell culture passage frequency depending on the specific parameters required of the cell culture in question based on metrics for healthy cell cultures that are known in the art.
Thus, the teachings of Kwak and ThermoFisher render obvious the invention as claimed.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al (Molecules and Cells (2015)38:3;229-235) as applied to claims 1, 4, 6, 8, and 9-11 above, and further in view of Mandel (Journal of Cellular Physiology(1983)114:1-10, cited previously) and TeSlaa et al (Methods Enzymol. (2014)542:91-114, cited previously).
This is a new rejection due to the claim amendments filed 10/08/2025, however relies on previously cited references.
Regarding claim 13: The teachings of Kwak are discussed supra. Kwak is silent on the state of glycolysis in the disclosed cell culture.
TeSlaa teach that glycolytic flux of cells in culture can be quantified by measuring glucose uptake and lactate excretion (p3 para 2).
Mandel teach fibroblasts that are depleted of NAM stop cell division and exhibit reduced glucose consumption and lactic acid production after three passages (abstract). Figure 4c shows cultures which are depleted of NAM consume little glucose (day 1-3) (p5 col 1 para 2). When cells are supplemented with NAD+ (day 3 boxes and triangles), glucose utilization and lactic acid production are rescued (glycolysis is enhanced) (Figure 4c and p 5 col 1 para 2).
Thus the teachings of TeSlaa and Mandel show that cells supplemented with NAD+ have enhanced glucose utilization. Kwak teach nicanomide is taken up by cells and converted to NAD+. Thus the cells of Kwak that are treated with nicanomide would have increased glucose utilization and thus enhanced glycolysis.
Therefore, the teachings of Kwak, TeSlaa and Mandel render obvious Applicant’s invention as claimed.
Response to Arguments
The responses are directed to the Arguments filed 10/08/2025, which have been fully considered.
Regarding Arguments directed to 35 USC § 112(b):
Applicant's arguments filed on 10/08/2025 have been fully considered and are persuasive.
Applicant submits claim 17 is canceled herein and accordingly, the rejection with respect to Claim 17 is moot. Applicant further submits claims 1, 5, 6, and 9 are newly amended to overcome the rejection.
This is persuasive because the amendments overcome the rejections and the rejection is withdrawn.
Regarding Arguments directed to 35 USC § 102:
Regarding claims 14-17: Applicant's arguments filed on 10/08/2025 have been fully considered and they are persuasive.
Applicant submits are canceled herein, and accordingly the rejection is moot with respect to the canceled claims. This is persuasive and the rejection in regards to the canceled claims 14-17 is withdrawn.
Regarding claims 1 and 4-7: Applicant's arguments filed on 10/08/2025 have been fully considered and they are persuasive.
Applicant submits that Cho et al. differ from the instant claim 1 because Cho et al. use NAD+ precursors in media to prevent senescence while the instant invention is drawn to rescuing a cell from induced senescence.
Cho teach the method steps as claimed in the instant invention. In regards to the senescent state of the cell culture disclosed by Cho, Cho teach nicotinamide (a NAD+ precursor) inhibits the induction of senescence (abstract), however Cho do not explicitly teach placing a senescent cell or cell line in a media comprising and NAD+ precursor or adding a NAD+ precursor to the culture media.
Thus the argument is found persuasive and the rejection in regards to claims 1 and 4-7 is withdrawn.
However a new rejection over 35 USC § 102 is entered.
Regarding Arguments directed to 35 USC § 103:
The rejection is withdrawn due to the claim amendments, however new rejections over 35 USC § 103 are entered and the arguments are addressed below.
Claims 5 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al (Molecules and Cells (2015)38:3;229-235) as applied to claims 1, 4, 6, 8, and 9-11 above, and further in view of Cho et al (US 2015/0072416, cited previously).
This is a new rejection due to the claim amendments filed 10/08/2025 but also relies on previously cited references.
Regarding claims 5 and 7-8: The teachings of Kwak are discussed supra. The disclosure of Kwak is drawn to the culture of human fibroblast cells. Kwak do not teach the cells comprise stem cells.
Cho teach the culture of H9 human embryonic stem cells in unconditioned medium, and cells treated with NAD+ precursors including nicotinamide (NAM) and NAD+ (p8/9 para 101). Cho further teach that H9 human embryonic stem cells are cultured with unconditioned medium (UM), which comprises DMEM and does not comprise non-human animal components (and thus reads on xeno-free culture medium) (p 10 para 0119).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Kwak drawn to rescuing a cell culture from senescence by using a stem cell culture as taught by Cho.
One of ordinary skill in the art would have been motivated to modify the method as taught by Kwak for the purposes of cultivating stem cells as taught by Cho because Cho teach nicotinamide inhibits the induction of senescence and oxidative stress and increases cell proliferation to improve culture conditions (p3 ¶0017).
One would have had a reasonable expectation of success because Cho discloses beneficial effects of nicotinamide treatment for stem cell culture.
Thus, the teachings of Kwak and Cho renders obvious the invention as claimed.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al (Molecules and Cells (2015)38:3;229-235) as applied to claims 1, 4, 6, 8, and 9-11 above, and further in view of ThermoFisher (ThermoFisher Datasheet (2014), retrieved from the internet May 5 2025 https://www.thermofisher.com/content/dam/LifeTech/migration/files/technical-reference-library/protocols/Protocol_CulturinghMSCsUnderSerumFreeAndXenoFreeConditions_FINAL.pdf, cited previously).
This is a new rejection due to the claim amendments filed 10/08/2025, however relies on previously cited references.
Regarding claim 12: The teachings of Kwak are described above.
Kwak does not teach cells are passaged at least once every 12-168 hours.
ThermoFisher protocol for culturing human mesenchymal stem cells (MSCs) under serum-free and xeno-free conditions teaches a passage schedule for three different media types (p 2/3 Table 1 “passage schedule”). The passage schedule taught by ThermoFisher ranges from 3-7 days (72-168h).
It would have been obvious for one who is skilled in the art to modify the cell culture method of Kwak with the teaching of ThermoFisher. Furthermore, one skilled in the art would understand that cell passage frequency depends on the specific conditions of a cell culture (cell density, cell type, media type etc.) and would use the teaching of ThermoFisher as a starting point to conduct routine optimization of the cell culture passage frequency depending on the specific parameters required of the cell culture in question based on metrics for healthy cell cultures that are known in the art.
Thus, the teachings of Kwak and ThermoFisher render obvious the invention as claimed.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Kwak et al (Molecules and Cells (2015)38:3;229-235) as applied to claims 1, 4, 6, 8, and 9-11 above, and further in view of Mandel (Journal of Cellular Physiology(1983)114:1-10) and TeSlaa et al (Methods Enzymol. (2014)542:91-114).
This is a new rejection due to the claim amendments filed 10/08/2025, however relies on previously cited references.
Regarding claim 13: The teachings of Kwak are discussed supra. Kwak is silent on the state of glycolysis in the disclosed cell culture.
TeSlaa teach that glycolytic flux of cells in culture can be quantified by measuring glucose uptake and lactate excretion (p3 para 2).
Mandel teach fibroblasts that are depleted of NAM stop cell division and exhibit reduced glucose consumption and lactic acid production after three passages (abstract). Figure 4c shows cultures which are depleted of NAM consume little glucose (day 1-3) (p5 col 1 para 2). When cells are supplemented with NAD+ (day 3 boxes and triangles), glucose utilization and lactic acid production are rescued (glycolysis is enhanced) (Figure 4c and p 5 col 1 para 2).
Thus the teachings of TeSlaa and Mandel show that cells supplemented with NAD+ have enhanced glucose utilization. Kwak teach nicanomide is taken up by cells and converted to NAD+. Thus the cells of Kwak that are treated with nicanomide would have increased glucose utilization and thus enhanced glycolysis.
Therefore, the teachings of Kwak, TeSlaa and Mandel render obvious Applicant’s invention as claimed.
Conclusion
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.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631