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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 23 January 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 23 June 2026.
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CLAIMS UNDER EXAMINATION
Claims 1-15 and 17 are pending. Claim 15 has been examined on the merits. Claims 1-14 and 17 are withdrawn.
PRIORITY
The Applicant claims priority to KR10-2013-0055158, filed on 15 May 2013.
NEW GROUNDS OF REJECTIONS
New grounds of rejection have been necessitated by claim amendment.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Ra et al. (previously cited; Culture of multi-potential stem cells originating in adipose tissue and a cosmetic composition containing protein extracted therefrom. WO2010008219 A2) in view of Furcht et al. (previously cited; Multipotent Adult Stem Cells And Methods For Isolation. US2018/0110806 with benefit of 11/238234 filed on 29 September 2005), Solchaga et al. (previously cited FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. Journal of Cellular Physiology 203:398–409 (2005), Toma (Fate Of Culture-Expanded Mesenchymal Stem Cells in The
Microvasculature: In Vivo Observations of Cell Kinetics. Circ Res. 2009 February 13; 104(3): 398–402), Wang et al. (Growth Inhibition of Mesenchymal Stem Cells By Aspirin: Involvement of the WNT/β-Catenin Signal Pathway. Clinical and Experimental Pharmacology and Physiology (2006) 33, 696–701) and Tatsumi et al. (previously cited; Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism. Biochemical and Biophysical Research Communications 431 (2013) 203–209).
Ra teaches method of culturing of adult adipose stem cells derived from human adipose tissue (Example 1, page 8). Adipose stem cells are cultured in “keratinocyte-SFM” containing 5% FBS, 2 mM NAC, 0.2 mM ascorbic acid, 0.09 mM calcium, 5 ng/ml rEGF, 5 μg/ml insulin and 74 ng/ml hydrocortisone. Multipotent mesenchymal stem cells are isolated (see Example 1, section (1), page 8). Adipose tissue-derived multipotent mesenchymal stem cells can be passaged for 3, 5, 8 or 10 (see Example 1, section (2), page 8).
Ra teaches adipose stem cell culture medium may be supplemented with additives that promote proliferation of the undifferentiated phenotype of adipose stem cells (see page 3, middle of page)
The medium can contain components found in most preservative media, including selenium (see page 3, middle of page).
Ra teaches in one aspect of the invention, human adipose tissue-derived adult stem cell cultures containing bFGF (see page 4, about fourth line). The art teaches the medium can contain bFGF (916.15 pg/ml) (see page 4, middle of page).
Ra teaches stem cells attached to a culture vessel can be treated with trypsin to recover the cells (see page 3, fifth section of Detailed Description of the Invention and Specific Embodiments).
Ra teaches a medium (composition) that contains
Keratinocyte serum free medium;
5% FBS;
the claimed amount of ascorbic acid;
the claimed amount of EGF;
the claimed amount of NAC;
the claimed amount of insulin ;
the claimed amount of hydrocortisone; and
the claimed amount of calcium.
Ra teaches adipose stem cell culture medium may also be supplemented with additives that promote proliferation. Ra teaches human adipose tissue-derived adult stem cell can be cultured with 916.15 pg/ml bFGF (hence, 0.916 ng/ml). Ra suggests the use of selenium to culture said cells.
The deficiencies of Ra are as follows:
Ra is silent regarding the amount of selenium.
Ra does not explicitly teach the culture medium contains 10 ng bFGF.
Ra does not teach preparing cells with a diameter of 10-15µm.
Ra does not teach suspending the stem cells in a solution containing the claimed amount of aspirin.
Ra does not teach preparing stem cells at a concentration of 1x107 to 5x108 cells/ml.
Furcht et al. disclose a method of culturing multipotent stem cells in medium (Abstract; [0026]). The art teaches “selenium may be present at a concentration of about 0.1 to about 5 μg/ml” ([0026]). Furcht also teaches the following:
The isolated cells have therapeutic uses (Abstract; [0002]). Undifferentiated cells can be injected for treatment ([0056]), including systemic injection ([0031]). Cells can be combined with a pharmaceutically acceptable carrier ([0215]). It is noted the art teaches administering 50,000 cells in Figures 14-15.
Solchaga expands mesenchymal stem cells in FGF-2 (hence, bFGF) supplemented medium (Abstract). Treated cells are smaller and proliferate more rapidly than hMSCs expanded without FGF-2 (Abstract; see page 401, left column, first paragraph of Results). The art uses a dose of 10 ng FGF-2 per ml (see Figure 2, see page 401, left column first two lines). Figure 2 discloses a liner dose-response relationship for cell growth (see text of Figure 2).
Toma teaches MSCs are used for cell based therapy (last paragraph of page 1).
Toma teaches the majority of MSCs systemically delivered are entrapped at the precapillary due to size (page 4, first paragraph of discussion; last paragraph). Toma teaches the large cell size is a direct consequence of the culture techniques, because freshly isolated human MSCs are smaller in size (10-μm diameter). Toma teaches different methods of MSC expansion may retain the original cell size and could result in improved intravascular rheology (page 4, third paragraph).
Tatsumi teaches MSCs are a therapeutic treatment (Abstract). High mortality rate is observed following intravenous infusion of adipose-derived MSCs (Abstract). Tatsumi teaches tissue factor is localized to the surface of cultured MSCs, triggering a pro-coagulative cascade activated by infused MSCs causing thromboembolism. Tatsumi teaches using an anti-coagulant agent to minimize intravascular coagulation (Abstract; see page 208, left column second paragraph)
Wang teaches mesenchymal stem cells (MSCs) are used for transplant therapy (page 696, left column, first paragraph). MSCs are treated for 20 hours with 1 mmol/L aspirin (page 697, left column, fourth paragraph; 1 mmol aspirin=1 x 180.16 (molar mass of aspirin) =180.16 mg/L= 0.18016 mg/ml.
Aspirin inhibits proliferation in a concentration dependent manner (page 697, last sentence of right column). The art teaches the growth inhibition is not the result of cytotoxicity (page 698, left column, last paragraph).
Wang teaches aspirin has anti-inflammatory, platelet inhibitory and anti-coagulatory effects (page 699, left column, first paragraph of “Discussion” section; page 700, left column, first paragraph). Wang suggests that aspirin may be favored in the later stage of MSC transplantation owing to its ability to prevent neoplasia from the transplanted cells in addition to is anti-coagulatory and anti-inflammatory effects (page 700, left column, first paragraph).
It would have been obvious to culture adipose tissue derived adult stem cells in a medium containing 1 ng/ml selenium. Ra teaches selenium can be used to culture multipotent adult stem cells and Furcht et al. teach about 0.1 to about 5 μg/ml selenium can be used to culture multipotent adult stem cells. The claimed amount is obvious because it lies inside the range taught by Furcht See MPEP 2133.03. One would have had a reasonable expectation of success since Furcht teaches selenium can be used in the claimed range. It would have been obvious to prepare cells at the claimed concentration. Furcht teaches the disclosed stem cells can be administered in a pharmaceutically acceptable carrier for systemic administration. While the art injects 50,000 cells, one would optimize the number of cells in a composition based on the desired dose. One would have expected similar results since Ra and Furcht are both directed to multipotent adult stem cells.
It would have been obvious to optimize the amount of bFGF in the medium taught by Ra. Solchaga teaches a dose of 10 ng bFGF per ml produces MSCs which are smaller and proliferate more rapidly. One would have been motivated to use bFGF at a concentration that produces smaller cells (10 ng) since Toma teaches the large size of MSCs can inhibit efficacy when administered intravenously. The skilled artisan would
want smaller cells to improve efficacy of systemic administration. The skilled artisan would optimize the amount of bFGF based on the desired cell number and cell size. See MPEP 2144.05. One would have had a reasonable expectation of success using bFGF since Ra teaches the use of additives that promote proliferation. One would have expected similar results since each reference is directed to therapeutic MSCs.
It would have been obvious to culture cells to passage 4 since Ra teaches culturing cells up for 3 or more days. The claimed stem cell increase is a result of culturing cells in the claimed culture medium. Because the claimed culture medium is rendered obvious, it follows that the stem cells taught by Ra would increase in number as claimed. It would have been obvious to treat the cultured cells with trypsin. One would have been motivated to do so to detach the cells from the culture dish as taught by Ra.
It would have been obvious to combine the teachings of the prior art by suspending the MSCs taught by Ra in a solution containing aspirin. Tatsumi teaches MSCs are a therapy that can be administered intravenously, but with high mortality due to coagulation. The skilled artisan would have been motivated to use aspirin since Tatsumi teaches using an anti-coagulant to reduce MSC coagulation and Wang teaches aspirin is an anti-coagulant that can be used to treat MSCs. One would do so when preparing cells for intravenous administration. One would have had a reasonable expectation of success since Wang teaches MSCs can be treated with aspirin without inducing cytotoxicity. Wang teaches a solution comprising 1 mmol/L aspirin. The skilled artisan would optimize the concentration based on desired cell proliferation.
The preamble of claim 15 recites the stem cells prepared by the disclosed method “are present as single cells”. The instant specification discloses this is a result of contact with aspirin (i.e. inhibiting aggregation) (page 20, lines 1-3). Because the prior art teaches contacting stem cells with a solution comprising aspirin, a culture containing aspirin would be expected to produce single cells as recited in the preamble of claim 15.
Therefore claim 15 is rendered obvious.
APPLICANT’S ARGUMENTS
The arguments made in the response field on 22 December 2025 are acknowledged. The Applicant argues the art does not teach culturing in the claimed concentration of aspirin for 12-24 hours.
EXAMINER’S RESPONSE
The arguments are not persuasive. New grounds of rejection are set forth above to address the amended claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653