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 .
Claims 1-4, 7 and 8 are pending in this application and were examined on their merits.
The objection to the Specification due to the improper use of Trademarks has been withdrawn due to the Applicant’s amendments to the Specification filed 01/30/2026.
The rejection of Claims 1-10 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inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, has been withdrawn due to the Applicant’s amendments to the claims filed 01/30/2026.
The rejection of Claim 8 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inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, has been withdrawn due to the Applicant’s amendments to the claims filed 01/30/2026.
The rejection of Claim(s) 1-9 under 35 U.S.C. § 102(a)(1) as being anticipated by
Park et al. (09/29/2020), cited in the IDS, has been withdrawn due to the Applicant’s submission of a certified translation of the Foreign Priority document.
The rejection of Claim(s) 1, 2, 3, 4, 5, 7 and 8 under 35 U.S.C. § 103 as being
unpatentable over Ahmed et al. (2016) in view of Park et al. (2012), both of record, has been withdrawn due to the Applicant’s amendments to the claims filed 01/30/2026.
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.
Claim(s) 1-4, 7 and 8 remain rejected under 35 U.S.C. § 103 as being unpatentable over Lavrentieva et al. (2010) in view of Lim et al. (US 2018/0267025 A1), as evidenced by Rajput et al. (2024), and further in view of Heidaran (US 2007/0134210 A1), all of record, for reasons of record set forth in the prior action.
Lavrentieva et al. teaches the incubation of primary umbilical cord derived
Mesenchymal Stem Cells (MSC) at 1.5-5% O₂ led to increased cells proliferation (Pg. 1
Abstract), wherein the cells were cultivated in αMEM medium comprising 10% human
serum and 50 µg/ml gentamicin for 4 days (24 hours + 72 hours) (Pg. 2, Column 2,
Lines 2-13), and reading on Claims 1, 2 and 8.
Lavrentieva et al. did not teach wherein hypoxia cultured stem cells are also
cultured under pressure conditions of 1-8 PSI or wherein the αMEM comprises 15% FBS and 0.5% gentamicin, as now required by Claim 1;
wherein the pressure condition is 2.0 PSI, as required by Claim 3;
wherein the pressure condition is 2.5 PSI, as required by Claim 4;
or wherein the culture is from 5-15 days, as required by Claim 7.
Lim et al. teaches a method comprising incubating a target cell subpopulation
under conditions of positive pressure and hypoxia (Pg. 13, Claim 32);
wherein the target cells are stem cells (Pg. 13, Claim 34);
wherein the stem cells are undifferentiated stem cells (Pg. 3, Paragraph [069]);
and wherein the positive pressure is at least about 2 PSI and the hypoxic condition is about 1-5% O₂ (Pg. 13, Claim 35).
Lim et al. further teaches the pressure of the environmental chamber can be set
to produce a force equal or greater than the average pressure present in capillaries of
the human vasculature system. Pressures can be set between 0.1 to 10 pounds per
square inch (PSI). The incubation conditions may vary depending on the type of cell to
be proliferated (Pg. 6, Paragraph [0126]).
Rajput evidences that stem cells, including umbilical cord MSC are
undifferentiated cells (Pg. 410, Abstract).
Heidaran teaches that placental stem cells (which include MSC) can be cultured
in any acceptable medium and conditions acceptable for the culture of stem cells,
including αMEM comprising 10% FBS and gentamicin (Pg. 10, Paragraph [0097]).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Lavrentieva et al. of culturing
primary umbilical cord derived Mesenchymal Stem Cells (MSC) under hypoxia
conditions to perform the culturing under positive pressure as taught by Lim et al.
because Lavrentieva et al. teaches culturing stem cells under hypoxia conditions and
Lim et al. teaches culturing undifferentiated stem cells (which umbilical cord MSC are)
under conditions of both hypoxia and positive pressure.
Those of ordinary skill in the art would have been motivated to make this modification because Lim et al. teaches that this would mimic the conditions found in the human vasculature system. There would have been a reasonable expectation of success in making this modification because both Lavrentieva et al. and Lim et al. are drawn to the same field of endeavor, that is, culturing stem cells under at least hypoxia conditions.
While the references listed above do not specifically teach the limitation of Claim
7, that the primary culturing is from 5 to 15 days, one of ordinary skill in the art would
recognize that the time in culture is a result-effective optimizable variable. Lavrentieva
et al. teaches culturing primary umbilical cord MSC for 4 days. This is a starting point
for the experimentation to determine the optimal time in culture. This is motivation for
someone of ordinary skill in the art to practice or test the culture time parameter values
widely to find those that are functional or optimal to sufficiently grow the cells to the
desired levels/amounts which then would be inclusive or cover the instantly claimed
values. Absent any teaching of criticality by the Applicant concerning the culture time, it
would be prima facie obvious that one of ordinary skill in the art would recognize these
limitations are an optimizable variable which can be met as a matter of routine
optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the
effective filing date of the claimed invention would have been motivated to make this
modification in order to obtain a primary umbilical cord derived MSC culture at the
desired concentration.
There would have been a reasonable expectation of success in making these modifications because all of the references are reasonably drawn to the same field of endeavor, that is, culturing stem cells under at least hypoxia conditions.
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Lavrentieva et al. of culturing
primary umbilical cord derived Mesenchymal Stem Cells (MSC) under hypoxia
conditions in an αMEM comprising 10% human serum and gentamicin to use an αMEM comprising 10% FBS and gentamicin as taught by Heidaran because both serums are known in the art to be suitable for culturing MSC. Those of ordinary skill in the art would have been motivated to make this modification based on the availability of αMEM, serum and artisan preference. There would have been a reasonable expectation of success in making this modification because both Lavrentieva et al., Lim et al. and Heidaran are generally drawn to the same field of endeavor, that is, culturing stem cells.
While the references listed above do not specifically teach the limitation of Claim
1, that the FBS is 15%, one of ordinary skill in the art would recognize that the serum concentration is a result-effective optimizable variable. Both Lavrentieva et al. and Heidaran teach culturing MSC in 10% serum media containing gentamicin.
This is a starting point for the experimentation to determine the optimal concentration of serum in the culture medium. This is motivation for someone of ordinary skill in the art to practice or test the culture media parameter values widely to find those that are functional or optimal to sufficiently grow/maintain the cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the concentration of serum and gentamicin in the culture media, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations as optimizable variables which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a viable primary umbilical cord derived MSC culture. There would have been a reasonable expectation of success in making these modifications because at least both the Lavrentieva et al. and Heidaran references are reasonably drawn to the same field of endeavor, that is, culturing MSC stem cells.
Response to Arguments
Applicant’s arguments, see Remarks, filed 01/30/2026, with respect to the above withdrawn objection/rejections have been fully considered and are persuasive.
The Applicant’s remaining arguments with regard to the pending rejections have been considered and are not found to be persuasive.
The Applicant argues that the cited references do not teach the currently claimed invention, noting that Heidaran (D7) discloses that umbilical-cord derived stem cells (including MSC) may be cultured in various media. Applicant concludes that there is no motivation for the ordinary artisan to select the claimed αMEM from the other culture media disclosed by the reference (Remarks, Pg. 9, Lines 16-21 and Pg. 10, Lines 1-2).
In response to Applicant's arguments against the references individually, 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). In this instance, Heidaran was cited only for its teachings of an αMEM comprising FBS at 10% along with gentamicin. Lavrentieva et al. teaches the incubation of primary umbilical cord derived Mesenchymal Stem Cells (MSC) at 1.5-5% O₂ led to increased cells proliferation (Pg. 1 Abstract), wherein the cells were cultivated in αMEM medium comprising 10% human serum and 50 µg/ml gentamicin for 4 days (24 hours + 72 hours) (Pg. 2, Column 2, Lines 2-13). Thus, it would have been obvious to those of ordinary skill in the art to modify the method of Lavrentieva of culturing
primary umbilical cord derived Mesenchymal Stem Cells (MSC) under hypoxia
conditions in an αMEM comprising 10% human serum and gentamicin to use an αMEM comprising 10% FBS and gentamicin as taught by Heidaran because both serums are known in the art to be suitable for culturing MSC. Those of ordinary skill in the art would have been motivated to make this modification based on the availability of αMEM, serum and artisan preference.
While the references listed above do not specifically teach the limitation that the αMEM contains FBS at 15% and gentamicin at 0.5%, one of ordinary skill in the art would recognize that the serum (and gentamicin concentration) are result-effective optimizable variables. Both Lavrentieva et al. and Heidaran teach culturing MSC in 10% serum media containing gentamicin. This is a starting point for the experimentation to determine the optimal concentration of serum in the culture medium. This is motivation for someone of ordinary skill in the art to practice or test the culture media parameter values widely to find those that are functional or optimal to sufficiently grow/maintain the cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the concentration of serum and gentamicin in the culture media, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations as optimizable variables which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a viable primary umbilical cord derived MSC culture. There would have been a reasonable expectation of success in making these modifications because at least both the Lavrentieva et al. and Heidaran references are reasonably drawn to the same field of endeavor, that is, culturing MSC stem cells.
The Applicant argues that Heidaran (D7) allegedly discloses gentamicin at a concentration of 50 µg/mL at Paragraph [0099], as opposed to the claimed 5000 µg/mL (.5%) (Remarks, Pg. 10, Lines 3-7).
This is not found to be persuasive for the following reasons, nowhere in the Heidaran reference is any concentration of gentamicin disclosed. The 50 µg/mL concentration derives from the Lavrentieva reference. As discussed in the prior action, the concentration of fetal bovine serum (and antibiotic/gentamicin) in the culture media is a result-effective variable subject to routine optimization and experimentation absent any showing of criticality and/or unexpected results.
The Applicant argues that Chang et al. (2006), Abstract discloses that when human bone-marrow derived MSC are cultured in gentamicin concentrations of 100 and 200 µg/mL the cells showed reduced proliferation, decreased DNA content and Alp activity related to osteogenesis. Applicant concludes that the ordinary artisan would not therefore be motivated to increase the amount of gentamicin in the Lavrentieva reference to the claimed concentration, noting the Specification examples showing initial cell yield is significantly improved (Remarks, Pg. 10, Lines 8-22 and Pg. 11, Lines 1-2).
This is not found to be persuasive for the following reasons, initially the Chang reference is directed to bone-marrow derived MSC and not the umbilical cord derived MSC of the claimed invention and the Lavrentieva reference. Secondly, the Applicant has not provided any evidence that the alleged “significantly improved” initial cell yield is due solely to the presence of the gentamicin in the absence of other culture conditions such as oxygen concentration and pressure, e.g. there is no evidence of criticality.
The Examiner maintains that the concentration of fetal bovine serum (and antibiotic/gentamicin) in the culture media is a result-effective variable subject to routine optimization and experimentation, absent any showing of criticality and/or unexpected results.
Conclusion
No claims are allowed.
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.
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 C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653