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 .
This application is now under examination by Examiner Valarie Bertoglio, AU 1632.
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/29/2025 has been entered.
Status of the Claims
Claims 9-11, 24,26, 28 and 30 are currently pending and under consideration.
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.
Claims 9-11, 24,26, 28 and 30 are 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 9 contains the trademark/trade name Orlistat. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Orlistat and, accordingly, the identification/description is indefinite.
Claims 10-11,24,26 and 28 are indefinite given their dependency from claim 9.
Claims 11 and 30 are unclear as to what is intended by “are obtained”. It is not known if this is an active method step or is reciting the effect inherent to the method carried out by claim 9. It appears Applicant may intend for claims 11 and 30 to further limit the differentiated cell type of claim 9. In that case, the claims would be more clear of they recited “wherein the purified and refined cells are cardiomyocytes” and “wherein the purified and refined cells are fibroblasts”.
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.
The previous rejection of claims 9-14, 18-21, 24 and 25 under 35 U.S.C. 103 as being unpatentable over Egusa (ref. of record) in view of Zhang et al. (Cell Stem Cell, 2012) and Pizer et al. (US 2002/0187534 A1, 2002) (ref. of record), as evidenced by PanReac AppliChem (α-MEM Product sheet, retrieved 09-02-2021) (ref. of record) and Yasumoto et al. (PLoS One, 2016) is withdrawn.
Claim(s) 9-11,26,28,30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Egusa (US PGPUB 20140356336/US 9,463,204, of record) view of Agostini (Mol Cancer Ther; 13(3) March 2014, pages 585-595) and Kridel et al. (Cancer Research, 2004, of record) and further in view of, Zhang et al. (Cell Stem Cell, 2012, of record) and Yasumoto et al. (PLoS One, 2016, of record) and Vazquez-MJartin (2012, Cell Cycle, 12:207-218).
Regarding claim 9, Egusa discloses a culture method comprising iPS cells (claim 10) cultured in the presence of differentiation medium that also contains statins [0200; 0217]. Egusa discloses statins (a differentiated cell purifying and refining agent) induce apoptosis selectively in undifferentiated stem cells [0173]. Therefore, Egusa teaches that statins cause cell death of undifferentiated cells selectively. Egusa further discloses [0145] there are no particular limits on the differentiated cells to which the differentiation induction method of the invention is applied, such as myocardial cells and fibroblasts. Thus, myocardial (cardiomyocytes) and fibroblasts are obtained (claim 11,30). Egusa discloses transplantation of the cells after induction in differentiation-inducing medium comprising simvastatin and further discloses that no tumor formation from the cell grafts were observed [0195].
Thus, Egusa teaches differentiating pluripotent stem cells into any differentiated cell type, including cardiomyocytes, in the presence of a statin to cause apoptosis of remaining pluripotent stem cells which can be tumorigenic if transplanted with the differentiated cell type. Egusa differs from the claims in that Egusa does not teach use of Orlistat, a lipase inhibitor, to selectively remove pluripotent stem cells from a differentiation culture.
However, Agostini taught Orlistat (tetrahydrolipstatin) is an irreversible inhibitor of fatty acid synthase (FASN), an enzyme that is responsible for the production of palmitate (palmitic acid, claim 26), and that Orlistat promotes apoptosis of tumorigenic cancer cells. Agostini uses Orlistat at varying concentrations from 50-200 mM. Similarly, Kridel used varying concentrations of Orlistat to treat tumor cells, including and effective concentration of 12.5 mM. The culture was carried out for either 48 or 72 hours, at which time, cell death was observed (claim 28).
The tumorigenic cells of Agostini are cancer cells, not pluripotent stem cells as is claimed. However, Zhang discloses that pluripotent stem cells and cancer cells have overtly similar metabolism (abstract). Zhang discusses how iPS cells have an elevated dependence on glycolysis under aerobic conditions compared to differentiated cell types such as cardiomyocytes and fibroblasts, and a high glycolytic flux, as also seen in cancer (pg. 589, right col., par. 2). Zhang further discusses other features shared between highly proliferative cancer cells and pluripotent stem cells (including iPS cells), as evidenced by Yasumoto. Yasumoto studied the expression and role of fatty acid synthase in glioma stem cells, and discloses that fatty acid synthase has been shown to be notably upregulated in both tumor and iPS cells, suggesting that fatty acid synthase is important for maintaining stemness (pg. 2, par. 2) Yasumoto references Vazquez-Martin who reports the marked overexpression and hyperactivity of FASN in both pluripotent and cancer cells.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time of the invention to carry out the method of Egusa involving differentiation of pluripotent stem cells in the presences of a statin with Orlistat as taught by Agostini. One would have been motivated to use Orlistat in the method of Egusa as Agostini and Kridel each taught the use of Orlistat to inhibit tumor formation by tumor cells, which are metabolically similar to pluripotent stem cells as taught by Zhang and Yasumoto. One would have had a reasonable expectation of success in substituting Orlistat for the statin in the method of Egusa because Zhang and Yasumoto each taught the metabolic similarities between pluripotent cells and tumorigenic cells and that FASN has an elevated role in both.
Given the data presented in Figure 3 of Agostino, it would not have been expected that 15mM of Orlistat would result in a population that comprises 95% differentiated cells, as is now required by claim 24.
Applicant’s Remarks
The previous rejection was withdrawn. However, it is noted that in Applicant’s remarks, they refer to Figure 4 of the Yasumoto reference. It appears they are referring to Figure 2. The argument refers to expression levels of genes G144,Y10. And G179 as not being significantly different between pluripotent and sifferenttiate4d cells. It is noted that G144, Y10, and G179 are cell lines, not genes. The data in Figure 2B of Yasumoto is not quantitative and statistical significance cannot be calculated. Figure 2B supports the downregulation of FASN upon stem cell differentiation.
Applicant also argues one would have expected a FASN inhibitor to adversely affect differentiated cells. Applicant does not provide support for this argument. The distinction between pluripotent stem cells/tumor cells and differentiated cells is that pluripotent and tumor cells are actively dividing at a rapid rate while differentiated cells are not.
Conclusion
No claims are allowed.
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/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632