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 .
Status of the Claims
Claims 1-21 are pending.
Claims 1 and 3 are newly amended.
Claims 6-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/10/2026.
Claims 1-5 have been examined on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 1-5 under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Hochedlinger et al. (WO2008/151058A2) as evidenced by An et al. (Stem Cell Reports, 2017) and Velychko et al. (Cell Stem Cell, 2019) is maintained but modified to address the claims as amended.
Claim Interpretation
Claim 1 as amended requires inducing non-pluripotent cells to express at least one reprogramming factor, “thereby transiently overexpressing desmosome-related genes or epithelial cell differentiation-related genes”.
As evidenced by Kim et al. (Anal Bioanal Chem, 2010), transient expression is a term of art that refers to the temporary expression of exogenous genes as contrasted with stable expression which integrates the exogenous gene into the host cell genome (Fig. 1, p3174).
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 1-5 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Hochedlinger et al. (WO2008/151058A2) as evidenced by An et al. (Stem Cell Reports, 2017) and Velychko et al. (Cell Stem Cell, 2019).
In regards to claims 1, 3, and 5, Hochedlinger discloses methods for the conversion (re-programming) of non-pluripotent stem cells (differentiated somatic cells) to induced pluripotent stem cells (iPSCs) (Claim 1). Hochedlinger discloses that this method comprises transiently inducing these cells to express reprogramming factors (e.g., Oct4, Sox2, Klf4, or c-Myc) (Claims 1 and 2; paragraphs [0010, 00116]).
In regards to whether this transiently overexpresses desmosome-related genes or epithelial cell differentiation genes, Applicant should note that transient overexpression of these genes is a natural consequence of performing the method steps of claim 1. Therefore, since the claim suggests that inducing a non-pluripotent cell to express a reprogramming factors is sufficient to cause transient overexpression of desmosome-related genes or epithelial cell differentiation genes, and since Hochedlinger carries out these steps the iPSCs as disclosed by Hochedlinger would express these genes absent evidence to the contrary.
Indeed, as evidenced by An, Oct4 overexpression itself during reprogramming of non-pluripotent cells to pluripotent cells in fact results in increased expression of Dsp (desmoplakin) (Figure 2E, p451); while as evidenced by Velychko, Oct4, Sox2, Klf4, and c-Myc reprogramming results in overexpression of Evpl (eviplakin) (Oct4 Overexpression Diverts Cells from a Direct Route to Pluripotency, p744; Figure 6C, p747).
In regards to claims 2 and 4, Hochedlinger discloses that iPSCs can be further differentiated into other cell types (paragraphs [0071, 0099]). It is noted that Hochedlinger achieves reprogramming of non-pluripotent cells by conditional expression in the presence of doxycycline (and that during differentiation doxycycline is removed (Fig. 3; paragraph [0040]). As a result, expression of Oct4 is significantly reduced (to near 0 relative expression, and is thus restricted) in these cells (Fig. 3C, paragraph [0040]). While Hochedlinger is silent as to the expression of Sox2, Klf4, or c-Myc in the absence of doxycycline, as their expression is dependent on the presence of doxycycline, a person of ordinary skill in the art would have recognized that their expression would also be similarly reduced or eliminated in the absence of doxycycline.
In regards to “then reducing the desmosome-related genes or epithelial cell differentiation genes”, as above, this is the result of cessation of Oct4, Sox2, Klf4, or c-Myc. As evidenced by An, Dsp levels are relatively reduced compared to Dox-Oct4 stimulated cells (Figure 2E, p451), while as evidenced by Velychko, Evpl is also relatively lower without dox-induced expression of Oct4, Sox2, Klf4, or c-Myc (Oct4 Overexpression Diverts Cells from a Direct Route to Pluripotency, p744; Figure 6C, p747).
Therefore, Hochedlinger anticipates the invention as claimed.
Response to Arguments
Applicant argues that Hochedlinger does not disclose each and each and every element as set forth in the claims as amended (Remarks, p7-8). In particular, Applicant argues that the claims as amended require “inducing the non-pluripotent cells to express at least one reprogramming factor, thereby transiently overexpressing desmosome-related genes or epithelial cell differentiation-related genes” (Remarks, p7-8).
Applicant argues Hochedlinger relates to a technique for obtaining ES cell-like iPSCs from fibroblasts through exogenous expression of Oct4, Sox2, c-Myc, and Klf4, and that the objective is to ultimately obtain iPSCs based on Nanog (Remarks, p7), but is entirely silent regarding transient expression of desmosome-related genes during the intermediate stage of reprogramming as recited in claim 1 as amended (Remarks, p7).
Applicant also argues that Hochedlinger is entirely silent regarding a separate population (gICs) simultaneously expressing markers such as Spink2 and Shisa3, distinct morphological characteristics, and low tumorigenicity, and therefore are distinguishable from the cells as claimed (Remarks, p10-11).
Applicant’s arguments filed 07/07/2026 have been fully considered but are not persuasive.
It is first noted that claim 1 does not require transient expression of desmosome-related genes during the intermediate stage of reprogramming nor a separate population (gICs) simultaneously expressing markers such as Spink2 and Shisa3 and with distinct morphological characteristics and low tumorigenicity.
Thus, In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., specific cells as above) are not recited in the rejected claim(s). 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).
In regards to the disclosure of Hochedlinger as they relate to the claimed as amended, Hochedlinger discloses methods for the conversion (re-programming) of non-pluripotent stem cells (differentiated somatic cells) to induced pluripotent stem cells (iPSCs) (Claim 1). Hochedlinger discloses that this method comprises transiently inducing these cells to express reprogramming factors (e.g., Oct4, Sox2, Klf4, or c-Myc) (Claims 1 and 2; paragraphs [0010, 00116]).
In regards to whether this transiently overexpresses desmosome-related genes or epithelial cell differentiation genes, Applicant should note that transient overexpression of these genes is a natural consequence of performing the method steps of claim 1. Therefore, since the claim suggests that inducing a non-pluripotent cell to express a reprogramming factors is sufficient to cause transient overexpression of desmosome-related genes or epithelial cell differentiation genes, and since Hochedlinger carries out these steps the iPSCs as disclosed by Hochedlinger would express these genes absent evidence to the contrary.
Indeed, as evidenced by An, Oct4 overexpression itself during reprogramming of non-pluripotent cells to pluripotent cells in fact results in increased expression of Dsp (desmoplakin) (Figure 2E, p451); while as evidenced by Velychko, Oct4, Sox2, Klf4, and c-Myc reprogramming results in overexpression of Evpl (eviplakin) (Oct4 Overexpression Diverts Cells from a Direct Route to Pluripotency, p744; Figure 6C, p747).
Applicant argues that while An discloses that Dsp (and epithelial marker) expression is increased under OCT4 induction or reprogramming, the references do not disclose that Dsp regulation is functionally involved in an intermediate stage of reprogramming as in claim 1, as amended (Remarks, p8).
Applicant also argues that Velychko only discloses that Evpl is overexpressed during OSKM-mediated reprogramming, but is unrelated to identifying an intermediate population (Remarks, p9-10). Applicant also argues that although Velychko discloses delayed expression of Nanog and Esrrb, such a disclosure merely means that the expression timing of those genes is shifted to a later stage, rather than remaining continuously in a low-expression state (Remarks, p10).
Applicant argues that by demonstrating that DSP knockdown decreases reprogramming efficiency, DSP overexpression increases programming efficiency (Remarks, p8-10). Applicant also argues that DSP regulation affects dIC/gIC formation (citing Examples 1-6 and 1-7; Remarks, p9-10). Therefore, Applicant argues that the pluripotent cells of An are fundamentally distinguishable from the pluripotent cells produced by the method of claim 1 (Remarks, p9).
Applicant’s arguments filed 07/07/2026 have been fully considered but are not persuasive.
Similarly to as above, claim 1 as amended does not require that Dsp regulation is functionally involved in an intermediate stage of reprogramming or identification of intermediate cells (gICs) as argued by Applicant. Claim 1 also does not require specific knockdown of Dsp either. Indeed, claim 1 does not require Dsp expression at all. Moreover, the claims themselves do not require Nanog or Essrb expression.
Thus, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. the effects of Dsp in regards to intermediate stage reprogramming or knockdown of Dsp, etc.) is not recited in the rejected claim(s). 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).
Instead, claim 1 only generically requires the active method step of “inducing the non-pluripotent cells to express at least one reprogramming factor.” As a result, the cells thereby overexpress desmosome-related genes or epithelial cell differentiation-related genes. Thus, transient gene expression is a property of the cells that occurs as a result of the active method step, which again, is only generically to induce non-pluripotent to express at least one reprogramming factor.
While claim 5 identifies Dsp as a desmosome or epithelial cell differentiation-related gene that is transiently overexpressed, as admitted by Applicant, Dsp expression is increased under OCT induction and reprogramming (see Remarks on 07/07/2026, p8). Therefore, since Hochedlinger discloses methods for the conversion (re-programming) of non-pluripotent stem cells (differentiated somatic cells) to induced pluripotent stem cells (iPSCs) (Claim 1) comprising inducing these cells to express reprogramming including Oct4(Claims 1 and 2; paragraph [0010]), these cells inherently exhibit increased levels of Oct4.
In regards to Applicant’s arguments about the PSCs of An being fundamentally distinguishable from the claimed cells, again, as admitted by Applicant, Dsp expression is increased under OCT induction and reprogramming (see Remarks on 07/07/2026, p8), and therefore, are undistinguishable from the cells as claimed.
Conclusion
No claims are allowed
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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