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 .
Application Status
This action is written in response to applicant’s correspondence received on 12/09/2025. Claims 1-8 and 10-24 are pending. Claims 1, 10-12, and 20-24 have been amended. Claim 9 has been cancelled. All pending claims are currently under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. This Office Action is Final.
Claim Rejections - 35 USC § 112 – Maintained/Updated in Response to Amendments
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 and 10-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Regents of the University of California v. Eli Lilly & Co, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regarding independent claims 1 and 12, these claims recite the protein PCBP1, encoded by a nucleic acid sequence that is at least 70% identical to SEQ ID NO: 1 encoding a protein that is at least 90% identical to SEQ ID NO: 2. Thus, claims 1 and 12 are reciting a genus of PCBP1 with a protein sequence at with up to 10% variation compared with SEQ ID NO:2 Furthermore, claims 1 and 12 are recited with functional limitations in the sense that the PCBP1 protein is associated with a method of the induction of pluripotent stem cells from differentiated cells, where furthermore the induction is not accompanied by tumorigenesis. Thus, the present invention is drawn to stem cell pluripotency, and its induction by the PCBP1 protein as well as mutant versions of this protein, where such cells are further recited to not be accompanied by tumorigenesis. This claim language is problematic because the Applicant has not sufficiently characterized mutant variants of the PCBP1 protein with up to 10% variation in the amino acid sequence and/or 30% variation in the nucleic acid sequence encoding the protein or, reduced to practice any functional analysis of its functional domains, nor performed sufficient mutational analysis of the protein to demonstrate possession of the scope of the claim. Thus, the Applicant has not demonstrated a representative number of species sufficient to show possession of the claimed genus.
With regards to the guidance provided in the specification, the Applicant offers Examples 1-8 (pages 29-48). The Applicant recites examples of PCBP1’s role in induced pluripotency (Example 1), efficacy studies of PCBP1 vectors in animal models (Example2), PCBP1 interaction studies with other transcription factors (Example 3), cardiac fibroblast induction (Examples 4-5), FACS detection of breast cancer cells (Example 6), effects of PCBP1 overexpression in cancer cells (Example 7), and the role of PCBP1 overexpression and its effect on BCL-2 and c-Myc (Example 8). Thus, the Applicant has examined effects of expressing/overexpressing PCBP1 in various contexts. The Applicant recites in Example 1, paragraph 119, reference to Figure 6B, which depicts two mutant variants of PCBP1 which according to the Brief Description of the Drawings, mutant 1 has one mutation while mutant 2 has two mutations (paragraph 19 and Figure 6). Thus, the Applicant has reduced to practice two embodiments of mutants, although the exact mutations are not recited in the specification.
The Applicant makes general reference to the presence of KH domains in PCBP1, and recites that the use of one or more KH domains “may selectively inhibit the translation of a given protein,” (paragraph 50). Further regarding the domains and residues of PCBP1, the Applicant recites that “Phosphorylation also plays a role in the activity of PCBPl (e.g. unphosphorylated PCBPl may lack activity). In some embodiments, the PCBPl nucleotide sequence contains mutations that affect the ability of the PCBPl polypeptide to be phosphorylated,” (paragraph 52). Thus, the Applicant recites that phosphorylation affects the activity of PCB1, where unphosphorylated embodiments of PCB1 “may” lack activity. The Applicant recites that the mutations V5M, Ll00P,LlO0Q, Cl09Y, Gl76E, P218S, S223L, D261Y, A272S, A316V, A345P, A345V, and E350Q affect phosphorylation but have not characterized such mutant variants. Thus, the Applicant teaches only general information regarding PCBP1, teaching that unphosphorylated PCB1 “may” lack activity, or that KH domains “may selectively” inhibit protein expression (above). However, phosphorylation sites which could disrupt activity by mutation have not been demonstrated and characterized, nor have methods or predicting such sites in PCB1 or the result of mutating potential phosphorylation sites.
The Applicant has not studied how individual mutations and/or variants of PCBP1 affect the proteins ability to function with relation to its interactions with, for instance other proteins/transcription factors and/or its target DNA. The Applicant has not characterized the functional domains of the protein in a manner sufficient to show possession of the claimed genus of mutant PCBP1 proteins, but has made only general reference to such domains or potential phosphorylation sites.
Furthermore, transcription factors, such as PCBP1, are known to be complex proteins with complex functionality. For instance, Lee (Lee TI et al. Cell. 2013 Mar 14;152(6):1237-51, of record) teaches that transcription factors are a part of complex cell regulation circuits involving thousands of other transcription factors, where changes in the regulation of transcription factors can have wide and varied cellular implications (Abstract). Lee teaches that transcription factors often bind to potential target elements by interacting with other transcription factors/proteins (page 1237, right column, final paragraph), and therefore teaches that different domains of transcription factors are critical to understand the varied and complex interactions which transcription factors are involved in. Lee teaches that transcription factors have complex roles and interactions with other proteins/transcription factors, DNA binding elements, cofactors, and nucleic acids (see pages 1237-1241). Thus, Lee teaches unpredictability concerning the genus of “mutant” or “variant” PCBP1 proteins because it is known that transcription factors are part of complex interaction networks. Given the complex interactions which transcription factors are known to comprise, precise understanding of their domains, and even key residues, is therefore critical to understand their overall role in a cell, as discussed by Lee. The Applicant has not characterized any such sequences of PCBP1 with up to 10% mutation, nor have they tested the 13 potential phosphorylation sites that they list (e.g., claim 12).
Furthermore, with specific regard to the limitation in the claims that the induction of pluripotency is not accompanied by tumorigenesis, Lee teaches that mutations in transcription factors have long been known to contribute to tumorigenesis (page 1242, right column, final paragraph). Mutational analysis of the transcription factor PCBP1 has not been performed by the Applicant, and given that mutations in transcription factor mutations are known to be associated with tumorigenesis the Applicant was not in possession of the claim limitation “is not accompanied by tumorigenesis.”
Further regarding the lack of possession of the claim limitation “not accompanied by tumorigenesis,” the Applicants have not reduced to practice any in vivo models of the present invention, and thus have not demonstrated by any experimental data that their systems are not accompanied by tumorigenesis because such a claim limitation would require testing within an organism capable of growing a tumor.
In conclusion, the Applicant did not show possession of the broad genus of PCBP1 transcription factor with 90% sequence identify to SEQ ID NO: 2 and/or 70% identity to the nucleic acid SEQ ID NO: 1 because they have not characterized the functional domains/interaction domains of PCBP1.
Furthermore, the dependent claims 2-8, 10-11, and 13-24 do not resolve these 112(a) issues and are therefore also rejected.
Response to Arguments
The Applicant’s arguments filed 12/9/2025 have been considered and are not persuasive. The Applicant argues that because they have recited a limitation in the claim (PCBP1 proteins that induce pluripotency and are not accompanied by tumorigenesis) the recited genus is far smaller than all variants. The fact that the genus, bounded by functional limitations, is far smaller than the “universe of all mutants” is irrelevant to whether or not the Applicant has shown possession of the genus that is “far smaller” than the universe of all mutants. In other words, the mere fact that the Applicant has provided a functional limitation in the claim does not implicitly mean that they have shown possession of the genus which would satisfy the functional limitations. In the present case, the Applicant has not reduced to practice any mutational analysis with the exception of two mutants, the mutations of which are not recited within the specification. The Applicant recites that the PCBP1 has multiple KH domains yet does not identify the domains. The Applicant recites that the phosphorylation state of the PCBP1 protein may inactivate its activity, and therefore acknowledges that individual residues of the PCBP1 protein are therefore critical to its functionality but only identifies 13 potential phosphorylation sites without testing them (see rejection, above).
The Applicant argues that the teachings of Lee are misplaced as used in the action. This argument is not persuasive, as Lee teaches that transcription factors and their mutations have long been known to be associated with tumorigenesis, where furthermore Lee lists several examples of such transcription factors (page 1242 final paragraph and page 1243). Thus, the fact that the Applicant has tested PCBP1 with two unidentified mutations (e.g., Figure 6B) hardly characterizes the genus of recited PCBP1 mutants. Given the fact that Lee teaches that mutations in transcription factors are known to cause tumorigenesis, and thereby teaches unpredictability in the art surrounding a genus of transcription factor with up to 10% of its residues mutated, a higher burden is placed upon the Applicant to show that such mutant PCBP1 proteins are not tumorigenic. This is especially true in light of the fact that no experimental testing has been done in vivo to show potential tumorigenicity. The Applicant’s arguments that PCBP1 appears to work to suppress tumor pathways is not persuasive because the Applicant is claiming a PCBP1/transcription factor mutant genus which is uncharacterized. The two mutants that the Applicant has tested is not sufficient to show possession of the limitation that the induction of the pluripotent stem cells is not associated with tumorigenesis with regards to the mutant PCBP1 proteins.
The Applicant argues that the claims are functionally self-limiting, and the specification teaches how to identify operative variants. This argument is not persuasive because the fact that the Applicant is claiming a functionally defined genus is insufficient to show possession of said genus. Furthermore, the specification lists 13 potential variants (also listed in claim 12), but in general the specification does not teach how to identify operative variants outside of these 13, which the Office does not concede the Applicant has demonstrated functionality for these 13 variants either as they have not been reduced to practice and tested.
The Applicant argues that the similarity sequence of 90% has been upheld if a consensus sequence is shown. This argument is not persuasive because the Applicant has not demonstrated or recited a “consensus” sequence, or core structural components to confer the recited functionality of the variant PCBP1 proteins. As the art teaches, variations in transcription factors can drastically change their functionality (Lee, above). The Applicant has not identified portions, domains, and/or individual residues which are amenable to mutation while retaining the recited functions of the claim.
The Applicant argues that mutational analysis has been performed. To this point, the Office acknowledges that limited mutational analysis has been performed (i.e., two mutants, Figure 6B).
The Applicant argues that a sequence plus one functional requirement is a recognized “relevant identifying characteristic.” This argument is not persuasive because of the unpredictability of the art and the requirement to characterize protein domains, especially in the case of transcription factors such as PCBP1, as transcription factors are part of complex cell networks and interact with a variety of other macromolecules (DNA, other proteins/transcription factors, see discussion on Lee, above). The Applicant’s species of mutants reduced to practice do not characterize the mutant genus as a whole owing to the complex and unpredictable nature of uncharacterized transcription factor mutants (Lee). The Applicant argues that the disclosure of a sequence, its identity thresholds, and two examples of mutating the sequence are sufficient to show possession of mutating the sequence up to 10%. This argument is not persuasive because the identification of a sequence and identifying it by functional limitations is not the same as showing possession of what modification would render such functional limitations.
Enablement -New Rejection in Response to Applicant’s Amendments
Claims 4, 12-22, and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of these in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
Regarding claim 12, claim 12 recite a method of inducing a pluripotent from a differentiated cell, where a vector is introduced into the differentiated cell comprising PCBP1 or a mutant/variant thereof. Thus, claim 12 is broadly drawn to a method where a differentiated cell can be induced to pluripotency by introducing PCBP1 itself on a vector. This claim language is problematic because it is known in the art that multiple transcription factors are required for induced pluripotency but claim 12 broadly encompasses a method where only PCBP1 is introduced to induce a differentiated cell into an induced pluripotent cell. Thus, a practitioner is not capable of using the invention, as the practitioner is not capable of making an induced pluripotent stem cell form PCBP1 alone (see below).
Regarding the guidance provided in the specification, the Applicant offers two examples where iPSCs are made (Example 1, retinal cells, and Example 4, cardiac cells). In both Examples 1 and 4, the factors Sox2, Oct4, and KLF4 are introduced in conjunction with PCBP1 to generate iPSCs, (e.g., paragraph 110 paragraph 140). For instance, the specification recites:
“All genes involved in the generation of iPSCs were inserted into one vector and transduced into retinal cells. Figure 1 shows a vector system that contains the strong human elongation factor-I alpha (EF) promoter to drive co-expression of genes for PCBPl, GFP (Fig 1A), as well as the genes for the transcription factors SOX2, Oct4, and KLF4,” (paragraph 110).
Thus, the Applicant has not reduced to practice the induction of iPSCs using PCBP1 alone.
Furthermore, it is known in the art that Oct4, Sox2, and KFL4 are required to induce iPSCs, as taught by Somner (Sommer CA et al. Stem Cells. 2009 Mar;27(3):543-9). Thus, it was known in the art that additional factors such as Oct4, Sox2, and KFL4 are known for iPSC induction, as the Applicant also appears to recite in their specification.
The specification is therefore not enabling for the invention recited in claim 12, where claim 12 is directed most broadly to the introduction of PCBP1 alone to induce a pluripotent stem cell. The specification is not enabling because a practitioner would not be able to use the invention, as the invention as recited would not be functional to make induced pluripotent stem cells.
Claims 13-22 and 24 depend from claim 12 and do not resolve this enablement issue. For instance, claims 20-22 do not recite that all three of the required Oct4, Sox2, and KFL4 transcription factors are required, which both Somner and the instant specification teach are needed to differentiate iPSCs (see above).
Furthermore, regarding claims 4 and 15, independent claims 1 and 12, from which these claims depend, have been amended and changed the scope of the claims. The amendments of the claims caused reconsideration of claims 4 and 15. Regarding claims 4 and 15, these claims recite that the method is carried out in vivo, and therefore include the induction of a differentiated cell into an iPSC in vivo. The application is not enabling for this method because it does not reduce such a method to practice, nor does the art teach that such a method is possible.
Regarding the specification, the Applicant has proposed only hypothetical animal model testing. The Applicant has therefore not reduced an in vivo method to practice, nor recited how such a method would be performed with sufficient explanation to enable a practitioner to carry out such a proposed method.
Regarding the state of the art, the art teaches that induced pluripotent stem cells require complex media formulations and growth conditions in order to both induce and maintain iPSCs. For instance, Rivera (Rivera T et al. Curr Protoc Stem Cell Biol. 2020 Sep;54(1):e117) teaches that complex, optimized media preparations and protocols are required to induce pluripotency, where such media and conditions are optimized under laboratory settings and conditions (e.g., page 18, left column, paragraphs 2-3 and see page 4 final paragraph to page 5, full page). Thus, it is known in the art that carefully designed culture media, culturing conditions, calibrated instrumentation, and growth conditions including essential media is required to induce iPSCs, where furthermore, in vivo induction of iPSCs by simply introducing PCBP1 alone (claim 15) or in combination with Oct4, Sox2, and KLF4 (claim 4) has not been reduced to practice or shown to be feasible as a method. Thus, a practitioner is not enabled to use the method as presently recited because the current understanding of the art is that such a method would not be feasible, where the Applicant has not reduced the method to practice to show that it is feasible.
Claim Rejections - 35 USC § 103 – New Rejection Necessitated by Amendment
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 5-8, 10-14, and 16-24 are rejected under 35 U.S.C. 103 as being unpatentable over Somner (Sommer CA et al. Stem Cells. 2009 Mar;27(3):543-9) in view of Shi (Shi H et al. 2018 Aug 7;37(1):187), Okano (Okano H et al. Circ Res. 2013 Feb 1;112(3):523-33), and Bakhmet 2 (Bakhmet et al. IOP Conf. Series: Journal of Physics: Conf. Series 917 (2017) 042027). The rejection is further evidenced by UniProt Q15365 (UniProt Accession number Q15365, which teaches the human PCBP1 protein, published 2006).
Regarding claim 1, Somner is a research article which teaches the use of single vector encoding Oct4, Sox2, and KFL4 (Abstract). Somner teaches that the vector is introduced into differentiated cells in order to generate induced pluripotent stem cells (Abstract). Somner further teaches that induced pluripotent stem cells (iPSC) have to potential to be used as therapeutics in humans (Introduction, first paragraph), and therefore teaches motivation to ensure the safety of such cells.
Somner does not teach that PCBP1 was introduced in the vector, or that the induction of the pluripotent stem cell is not accompanied by tumorigenesis. Somner does not teach SEQ ID NO: 2 (i.e., huma PCBP1).
Regarding PCBP1 and its connection with Oct4, Bakhmet 2 teaches that PCBP1 is known to bind to the enhancer element of the Oct4 gene (e.g., page 4, first paragraph). Furthermore, Bakhmet 2 teaches that it was known that Oct4 gene regulation is indispensable for iPSC induction, that it has “very delicate” regulation which include a number of enhancer elements (Introduction). Furthermore, Bakhmet 2 teaches that PCBP1 was known to regulate the expression of several genes (page 4, first paragraph). Thus, Bakhmet 2 teaches that the transcription factor PCBP1 was known to associate with the critical Oct4 gene at an enhancer, that the regulation of the expression of Oct4 is very sensitive, and that PCBP1 is known to regulate genes (above). Bakhmet 2 has therefore taught a motivation to include PCBP1 within a vector, in order to reproduce the sensitive gene expression of Oct4.
Furthermore, Okano is a review article that focuses on the use of induced stem cells in therapies, as well as pitfalls with using such cells (Title, Abstract, and throughout). Okano therefore directly overlaps with Somner, as both teach stem cells, their potential as a therapeutic, and potential safety and design concerns with using stem cells. Okano teaches that a known concern and problem with using induced stem cells is their potential to cause tumorigenicity (e.g., Abstract, page 524 left column first paragraph). Thus, Okano teaches that it was known in the art that induced stem cells have the potential to cause tumorigenicity, and that such a problem needs to be addressed in the field.
Regarding PCBP1 and its role in tumorigenesis, Shi is a research article which evaluated the role of PCBP1 in tumorigenicity (Title, Abstract, and throughout). Given that Bakhmet 2 has already taught PCBP1 as a transcription factor associated with iPSC/Oct4, the teachings of Shi and Bakhmet 2 overlap in subject matter because they both focus on the same protein (i.e., PCBP1). Furthermore, Shi teaches that the deletion of PCBP1 promotes tumorigenesis (Title, Abstract, throughout). In addition, Shi teaches that the overexpression of PCBP1 inhibits tumorigenesis (second page, left column, third paragraph). Thus, Shi teaches a motivation to overexpress PCBP1, as it is known to inhibit tumorigenesis, which is a known safety concern in iPSC induction per Okano (above). Thus, not only was PCBP1 a known protein that associated with Oct4 and its transcription enhancers (Bakhmet 2) it was also known to have a beneficial property of inhibiting tumorigenesis which was a known problem in iPSC induction at the time. Furthermore, Shi teaches that they used human PCBP1 on a vector (page 3, left column, final paragraph). As evidenced by UniProt Q15365, an alignment of instant SEQ ID NO: 2 to Q15365 is shown on page 1, where SEQ ID NO: 2 is shown to be the known huma PCBP1 sequence (UniProt Q15365, page 1 for alignment). Thus, Shi inherently teaches SEQ ID NO: 2 by teaching human PCBP1.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to combine the iPSC-inducing vector taught by Somner which includes Sox2, Oct4, and KFL4 to further include the PCBP1 gene as taught by both Shi and Bakhmet 2, as such a combination is the simple combination of know prior art elements with predictable success. In the present case, the practitioner would simply include PCBP1 with Somner’s vector, where such iPSC systems have been reduced to practice per Somner. Furthermore, the combination is not simply the combination of known parts: a practitioner would be specifically motivated to include PCBP1 in a vector for several reasons. Firstly, PCBP1 was known to inhibit tumorigenesis (Shi), where tumorigenesis was already a known safety problem with induced PSCs (Okano). Thus, a practitioner would be motivated to include PCBP1 as a known solution to a known problem of tumorigenesis in iPSC induction. Furthermore, the result is predictable because PCBP1 is not only identified with the beneficial property of inhibiting tumorigenesis, it is also already known to be a transcription factor associated with the critical Oct4 gene (Bakhmet 2). Thus, a practitioner would not only be motivated to include PCBP1 for its known tumor inhibiting properties, but would also be motivated to include it to maintain the “very delicate” regulation of Oct4, to maintain efficient iPSC induction, per Bakhmet 2 (Abstract). The results are predictable because vectors encoding transcription factors to be used for induction of iPSCs from differentiated cells have already been reduced to practice per Somner (Abstract).
Regarding claims 2-3, Somner teaches that such methods can be performed in vitro/ ex vivo (Introduction, first paragraph).
Regarding claims 5-7, Somner teaches that the cells are post-natal fibroblasts.
Regarding claim 8, Okano teaches that iPSCs can be used for treatment of heart diseases (e.g., page 530, left column final paragraph). Thus, it would be obvious to a person of ordinary skill in the art to apply the methods of Somner to cardiac cells.
Regarding claims 10-11, Somner teaches that the vector comprises Oct4, Sox2, and KFL4. (Abstract).
Regarding claim 12, the vector rendered obvious by Somner, Okano, Shi, and Bakhmet 2 would comprise PCBP1, where Shi teaches human PCBP1 with the same sequence as SEQ ID NO: 2 (see rejection of claim 1). Furthermore, Shi teaches that the expression of PCBP1 inhibits tumorigenesis (see rejection of claim 1, above).
Regarding claims 13-14, Somner teaches that such methods can be performed in vitro/ ex vivo (Introduction, first paragraph).
Regarding claims 16-18, Somner teaches that the cells are post-natal fibroblasts.
Regarding claim 19, Okano teaches that iPSCs can be used for treatment of heart diseases (e.g., page 530, left column final paragraph). Thus, it would be obvious to a person of ordinary skill in the art to apply the methods of Somner to cardiac cells.
Regarding claims 20-23, Somner teaches that the vector comprises Oct4, Sox2, and KFL4. (Abstract).
Regarding claim 24, Somner teaches that each transcription factor can be introduced on a second vector, simply as an alternative design (Abstract). Thus, a practitioner could immediately envision placing PCBP1 on its own vector.
Response to Arguments
The Applicant’s arguments filed 12/09/2025 have been considered and are persuasive. As such, the original prior art rejections are withdrawn. However, the Applicant’s amendments, including the identification of the cell (i.e., the differentiated cell) into which the vectors are being introduced has prompted reconsideration and an additional search. As such, a new 103 rejection is presented, above. As discussed in the above rejection, the introduction of PCBP1 into cells was already known to inhibit tumorigenesis, which was a known problem associated with iPSC induction (Okano, Shi). Furthermore PCBP1 was also already known to bind with the enhancer region of the critical Oc4 gene, whose transcription was known to be very sensitive (Bekhmet 2, Abstract). Thus, a practitioner would be motivated to include PCBP1 in iPSC induction schemes, as it was known to be an inhibitor of tumorigenesis, a known problems with iPSC induction, and furthermore was known to be a protein associated with the expression region of Oct4 (Bekhmet 2). Thus, the Applicant has neither identified PCBP1 as a novel protein associated with iPSC genes nor have they discovered the tumor inhibitory properties of PCBP1. Thus, the present invention does not appear to comprise an inventive concept.
The Applicant’s arguments regarding the original 112(a) rejection are persuasive, and have been withdrawn. The Applicant appears to have characterized portions and mutations of SEQ ID NO: 2, per their argument, and were therefore reasonably in possession of the invention.
Conclusion
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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/D.C.R./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635