Prosecution Insights
Last updated: April 19, 2026
Application No. 17/251,587

USE OF FIBROBLASTS AND/OR MODIFIED FIBROBLASTS FOR THREE DIMENSIONAL TISSUE PRINTING

Non-Final OA §103§112
Filed
Dec 11, 2020
Examiner
REGLAS, GILLIAN CHELSEA
Art Unit
1632
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Figene LLC
OA Round
5 (Non-Final)
25%
Grant Probability
At Risk
5-6
OA Rounds
3y 5m
To Grant
86%
With Interview

Examiner Intelligence

Grants only 25% of cases
25%
Career Allow Rate
12 granted / 48 resolved
-35.0% vs TC avg
Strong +61% interview lift
Without
With
+60.6%
Interview Lift
resolved cases with interview
Typical timeline
3y 5m
Avg Prosecution
53 currently pending
Career history
101
Total Applications
across all art units

Statute-Specific Performance

§101
7.5%
-32.5% vs TC avg
§103
38.5%
-1.5% vs TC avg
§102
15.3%
-24.7% vs TC avg
§112
31.3%
-8.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 48 resolved cases

Office Action

§103 §112
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 . 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/28/2026 has been entered. Claim Status As of the Final Office Action mailed 7/28/2025, claims 1-6, 10, 12-18, 21, 23-24, 29-30, 32-33, 35-38, and 43 were pending. In Applicant's Response filed on 1/28/2026, claims 1, 4-5, and 13 were amended, claim 3 was canceled, and claim 44 is newly added . As such, claims 1-2, 4-6, 10, 12-18, 21, 23-24, 29-30, 32-33, 35-38, and 43-44 are pending and have been examined herein. Withdrawn Objections/Rejections The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objection/rejections not specifically reiterated are hereby withdrawn. Argument related to previously cited references Kwon, Wadsworth, Furukawa, Maldonado, Han, Mathieu, and Pennarossa are moot because the new ground of rejections do not rely on any of these references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The declaration filed by Dr. Ichim (herein “Ichim declaration”) has been fully considered but not found persuasive. New Grounds of Rejections Claim Rejections - 35 USC § 112(b) 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 1-2, 4-6, 10, 12-18, 21, 23-24, 29-30, 32-33, 35-38, and 43-44 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 1 recites “using said dedifferentiated fibroblasts, or differentiated cells produced therefrom, in a bioprinting process to produce the organ, organoid and/or tissue”. It is unclear whether the using step as claimed is an active method step as it is recited in such a general manner. The only actual step recited is the culturing human fibroblasts. Moreover, if the “using” step is an intended use, there would be no nexus between cultured, undifferentiated cells and the objective of the preamble as claimed. Thus, the claim is indefinite. Claims 2, 4-6, 10, 12-18, 21, 23-24, 29-30, 32-33, 35-38, and 43-44 are included in this rejection for being dependent on indefinite claim 1. Claim 5 recites “treated with one or more additional epigenetic modifiers”. This lack antecedent basis as there is no previous recitation of the treatment with any initial epigenetic modifiers in the claim or in claim 1. Thus, the claim is indefinite. Claim 6 is included in this rejection for being dependent on indefinite claim 5. Claim 33 recites “said dedifferentiated fibroblasts are differentiated into cells of a desired type.” The term “desired type” is a relative term which renders the claim indefinite. The term “desired type” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is indefinite. The term “desired shape” in claims 36-37 is a relative term which renders the claim indefinite. The term “desired shape” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is indefinite. The term “desired organ” in claim 38 is a relative term which renders the claim indefinite. The term “desired organ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is indefinite. Claim 44 is an incomplete sentence. The claim does not contain period, making it unclear whether Claims 1-2, 4-6, 10, 12-18, 21, 23-24, 29-30, 32-33, 35-38, and 43-44 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the steps to generate an organ, organoid, and/or tissue. The claim generically claims “using said dedifferentiated fibroblasts, or differentiated cells produced therefrom, in a bioprinting process to produce,” but fails to actually claim any active method steps to achieve the goal of generating a human organoid, organ, or tissue. Claims 2, 4-6, 10, 12-18, 21, 23-24, 29-30, 32-33, 35-38, and 43-44 are included in this rejection for being dependent on indefinite claim 1. It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to rejections made based on said interpretations. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action. Claim Rejections - 35 USC § 103 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claim(s) 1-2, 4, 5-6, 14-15, 23, and 32-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al (US 9528092 B2, 7/30/2009; published 12/27/2016). Yamanaka teaches method of improving the efficiency of establishment of mouse or human induced pluripotent stem (iPS) cells, comprising: a) introducing into mouse or human somatic cells an expression vector or expression vector expression vectors comprising nucleic acids encoding any of the following (i) to (ii): (i) Oct3/4, Klf4 and Sox2, (ii) Oct3/4, Klf4, Sox2 and c-Myc, and b) culturing the somatic cells from a) in ES cell culture medium, under hypoxic conditions wherein the oxygen concentration is 5%, thereby improving the efficiency of the establishment of iPS cells compared to the establishment efficiency of mouse or human iPS cells produced by the same method at an atmospheric concentration of oxygen (see claim 1 of Yamanaka) (“wherein said hypoxic conditions comprise a reduced oxygen range between 0.2-5%” as in instant claim 4; “wherein said fibroblasts . . . are subjected to hypoxic conditions” as in instant claim 23). The working examples discuss utilizing adult human dermal fibroblasts (see example 7 of Yamanaka) (“wherein said fibroblasts are selected from the group consisting of dermal fibroblasts” as in instant claim 2). The reference recites that valproic acid is used to improve the efficiency of establishing the induced pluripotent stem cells (see claim 2 of Yamanaka). It also states that the culturing somatic cells under hypoxic conditions is performed for more than 3 days after introducing the expression vector or vectors into the somatic cells and the somatic cells are fibroblasts (see claims 3 and 6 of Yamanaka). The reference teaches that there are various substances that improve efficiency of establishment of iPS cells, including histone deacetylase (HDAC) inhibitors [e.g., valproic acid (VPA) (Nat. Biotechnol., 26(7): 795-797 (2008)], low-molecular inhibitors such as trichostatin A, sodium butyrate, MC 1293, and M344, nucleic acid-based expression inhibitors such as siRNAs and shRNAs against HDAC, HuSH 29mer shRNA Constructs against HDAC1, and the like, DNA methyltransferase inhibitors (e.g., 5′-azacytidine), G9a histone methyltransferase inhibitors [e.g., low-molecular inhibitors such as BIX-01294 (“iPS cell establishment efficiency improvers para 2) (“wherein said culturing step comprises culturing of the fibroblasts in a culture medium treated with one or more additional epigenetic modifiers” as in instant claim 5 and “wherein said epigenetic modifier is a DNA demethylating agent, histone deacetylase inhibitor, histone modifier, or a combination thereof” as in instant claim 6). Fig. 3 shows at least NANOG expression in the induced pluripotent stem cells. This reads on “culturing human fibroblasts under suitable conditions to induce dedifferentiation of the fibroblasts, wherein the suitable conditions do not include OCT-4 comprise hypoxia and valproic acid; . . . , wherein said dedifferentiated fibroblasts express detectable levels of NANOG.” as in instant claim 1. The reference also teaches that the human fibroblasts and iPS cells can be further cultured in the presence of bFGF (“wherein said fibroblasts are cultured using a culture medium treated with one or more growth factors” as in instant claim 14 and “wherein said growth factors are selected from the group consisting of . . . , FGF-2” as in instant claim 15). Human iPS cells established by introducing the four genes Oct3/4, Klf4, Sox2, and c-Myc and culturing the starting cells at 5% oxygen concentration between day 7 to day 40 after the infection were sown to low-binding dishes, and cultured for 8 days to form embryoid bodies (EB) (100 mm dishes). After being cultured for 8 days, the embryoid bodies were stained using antibodies against the endodermal cell differentiation marker α-fetoprotein, the mesodermal cell differentiation markers smooth muscle actin, Desmin, and Vimentin, and the ectodermal differentiation markers βIII-tubulin and GFAP. The results are shown in FIG. 12. This staining confirmed the expression of these markers, demonstrating that the human iPS cells established possessed the potential for tridermic differentiation (“wherein dedifferentiated fibroblasts and/or differentiated cells produced therefrom are of an endodermal, ectodermal, or mesodermal lineage” as in instant claim 32). The iPS cells thus established can be used for various purposes. For example, by utilizing a reported method of differentiation induction for ES cells, differentiation of the iPS cells into various cells (e.g., myocardial cells, blood cells, nerve cells, vascular endothelial cells, insulin-secreting cells and the like) can be induced (“wherein said dedifferentiated fibroblasts are differentiated into cells of a desired type” as in instant claim 33). While Yamanaka does not explicitly teach using the dedifferentiated fibroblasts to produce an organ, organoid, or tissue, it is an intended use of the dedifferentiated fibroblasts. Moreover, the selection of a known material (in this case, induced pluripotent stem cells) based on its suitability for its intended use supports a prima facie obviousness determination (see MPEP 2144.07; see Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to dedifferentiate fibroblasts into induced pluripotent stem cells as taught by Yamanaka where the cells are able to be used in a bioprinting process, to arrive at the instantly claimed invention. One of ordinary skill would have been motivated to dedifferentiate fibroblasts using valproic acid and hypoxia for the purpose of using for bioprinting with a reasonable expectation of success as the selection of a known material (in this case, induced pluripotent stem cells) based on its suitability for its intended use supports a prima facie obviousness determination. Claim(s) 17-18, 21, 24, 29-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka as applied to claims 1-2, 4, 5-6, 14-15, 23, and 32-33 above, and further in view of Bhatia et al (WO 2014/039429 A1, 13 March 2014; previously cited). The difference between the combined teachings and the invention as instantly claimed is that they do not teach the fibroblasts are cultured as a plurality of cell aggregates prior to bioprinting (related to claim 17), the cell aggregates being seeded in extracellular matrix (related to instant claim 18), and that the extracellular matrix is configured into the form of a defined shape or the cell aggregates seeded in extracellular matrix are introduced into a mold having the defined shape (related to instant claim 21). It also does not disclose that a hydrogel or synthetic polymer is admixed or deposited onto the cells and/or cell aggregates (related to instant claims 29 and 30). Bhatia teaches a method of generating three-dimensional tissues using a variety of cells and a bioprinter (abstract) as an alternative to standard transplantation approaches (p. 1, para 0003). It teaches that bioprinting is the deposition of living cells, as well as other components (ECM, cells in combination with hydrogels) (p. 8, para 0036) and that an inkjet printing device used can include a 2D or a 3D printer (p. 8, para 0038). The types of cells used can be syngeneic, allogeneic, xenogeneic, obtained from a donor, or derived from an established cell strain or cell line (p. 12, para 0052). Cell types that can be used in the method include stem cells such as induced pluripotent stem cells (p. 13, para 056). The cells used can be deposited on a surface as aggregates that comprise multiple cells types or the cells are formulated in compositions such that the cells form a tissue as part of the composition and the tissue is deposited on the surface (p. 22, para 0091 and 0092). In order for the cells to be deposited as aggregates or for the cells to form tissues prior to deposition, they would need to be cultured as such first, which reads on instant claim 17. Example 1 (p. 42) describes the fabrication of hybrid scaffolds comprising synthetic material and extracellular matrix, where the synthetic material is polycaprolactone and the scaffold was seeded with placental stem cells. This example demonstrates that scaffolds comprising ECM are suitable for the attachment and growth of cells (p. 42, para 00194). The cells not only attach, but survive and proliferate when cultured on the scaffold (p. 44, para 00199). While this example uses placental stem cells, a variety of stem cells can be used including induced pluripotent stem cells and reprogrammed stem cells (p. 13, para 055), which could be single cells, aggregates, or preformed tissue as previously described. This means that there are multiple cell types useful for the same purpose of 3D bioprinting, which reads on instant claim 18. Methods for derivatization of ECM and synthetic polymers are known in the art, and include, without limitation, derivatization using cell attachment peptides (e.g., a peptide comprising one or more RGD motifs), derivatization using cell attachment proteins, derivatization using cytokines (e.g., vascular endothelial growth factor (VEGF), or a bone morphogenetic protein (BMP)), and derivatization using glycosaminoglycans (para 122) (“wherein said extracellular matrix is cultured using a culture medium treated with one or more cell attachment peptides, one or more cell attachment proteins, one or more cytokines, one or more glycosaminoglycans, or a combination thereof” as in instant claim 24). Bhatia also teaches that the artificial surface in which the cells and extracellular matrix are deposited are engineered to form a particular shape, such as a bone (p. 31, para 00140) (reads on instant claim 21). An artificial surface may be engineered so that is the shape of a bone, and the appropriate cells (e.g., osteocytes, osteoblasts, osteoclasts and other bone -related cells) and flowable ECM on and/or in said surface (p. 31, para 00140). It also teaches that a hydrogel is deposited with the extracellular matrix and cellular composition (see claim 19 of Bhatia) (reads on instant claim 29), the hydrogel may be deposited concurrently with, before, or after the deposition of the extracellular matrix (p. 27, para 00117) and that there is a deposition of a synthetic polymer (see claims 23-29 of Bhatia) concurrently with, before, or after the deposition of the ECM (p. 28, para 00120) (reads on instant claim 30). Example 2 shows that a hybrid scaffold consisting of ECM and a synthetic material such as PCL can maintain an intact structure throughout the duration of cell culture, that PCL provided good structural support for the ECM hydrogels, and that the cells bioprinted along with the components of the of the hybrid scaffolds proliferate on the scaffolds and intersperse better than when cultured in cellular matrix alone (p. 45, section 5.2.3, para 00204). Therefore, it would have been obvious to induce the dedifferentiation of fibroblasts into induced pluripotent stem cells, as taught by Yamanaka, where the fibroblasts are cultured as aggregates as taught by Furukawa, where the cells are seeded in extracellular matrix during the bioprinting process, as taught by Bhatia, and arrive at the instantly claimed invention. One of ordinary skill would have been motivated to seed cell aggregates in extracellular matrix because ECMs are suitable substrates for the attachment and growth of cells. Seeding cell aggregates in extracellular matrix has been shown to work in the case of the prior art with a reasonable expectation of cell attachment, survival, and proliferation on the ECM. It also would have been obvious to induce the dedifferentiation of fibroblasts into induced pluripotent stem cells, as taught by Yamanaka, and define the shape of the ECM seeded with cells aggregates, as taught by Bhatia, and arrive at the instantly claimed invention. One of ordinary skill would be motivated to do so because the ECM/cell aggregates can form a particular shape, such as a specific bone, to be used as a replacement instead of traditional transplantation techniques. There is a reasonable expectation of success to define the shape of the ECM alone or the ECM seeded with cells using an artificial surface since it has been shown to work in the case of the prior art. Furthermore, it would have been obvious to induce the dedifferentiation of fibroblasts into induced pluripotent stem cells, as taught by Yamanaka, and mix a hydrogel during deposition or to deposit a synthetic polymer onto the cells or cell/hydrogel mixture, as taught by Bhatia, because ECM hydrogels, particularly those having a synthetic polymer such as PCL, maintain an intact structure throughout the duration of cell culture. The cells bioprinted along with the components of the of the hybrid scaffolds proliferate on the scaffolds and intersperse better than when cultured in cellular matrix alone. Finally, it would have been prima facie obvious to try, from a finite number of identifiable, predictable solutions, to culture cells used in a 3D bioprinting process as aggregates prior to printing as claimed with a reasonable expectation of success because cells used in these processes can be single cells, aggregates of multiple types of cells, or even tissues derived from cells as taught by the prior art. Response to Arguments Applicant did not provide any arguments or challenge the specific teachings of previously cited reference Bhatia. Claim(s) 35-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka as applied to claims 1-2, 4, 5-6, 14-15, 23, and 32-33 above, and further in view of Boland et al (US 7051654 B2, previously cited) and Bhatia et al (WO 2014039429 A1; previously cited). The difference between the combined teachings and the invention as instantly claimed is that they do not teach the bioprinter is a three-axis mechanical platform that controls movement of extruders that deposit living cells in a desired shape (related to instant claim 36), and that the desired shape is acquired by scanning the surface of a desired organ/organoid/tissue to generate a surface map using a laser, electron beam, magnetic resonance imaging, microwave, x-ray, computed tomography, or a combination thereof (related to instant claims 37 and 38). Boland teaches a method for forming an array of viable cells using ink-jet printing a cellular composition containing cells onto a substrate (see claim 1 of Boland), where the cellular composition contain eukaryotic cells (see claim 12 of Boland) and cell aggregates (see claim 13 of Boland) in a three-dimensional array (see claim 25 of Boland). This inkjet printer is relatively inexpensive, quick, and efficient in depositing arrays of viable cells (col 1, lines 61-63). Figures 1 and 20 in combination show that the inkjet printer’s components are capable of moving in the x-, y-, and z-axes to create the 3D printed tissue (“wherein said bioprinting comprises three-dimensional printing of a biological organ, organoid, and/or tissue through the layering of living cells using a bioprinter” as in instant claim 35). Specifically, Fig. 20 shows how the layers are deposited onto a substrate using the printer of Fig. 1 such that the printer head moves in the x and y direction and the stage can move in the y- and z-directions (col 11, lines 27-37). The reference also teaches that terminally differentiated adult cells have the capacity to be a source for retro differentiation to bipotential, pluripotential, or totipotent stem cells (col 15, lines 15-20). The scaffolds used in the reference can be populated with adult-derived cells that are capable of undergoing subsequent differentiation after being cultivated in vitro, including cells of the skin, cartilage, muscle, among others (col 11, lines 29-34). This reference shows that inkjet bioprinting can be used to deposit layers of viable cells (including adult-derived cells of the skin) across three-axes, which reads on instant claim 36. Bhatia teaches a method of forming three-dimensional tissues. The method of forming the three-dimensional tissue includes scanning the desired surface (“scanning the surface of a desired organ” as in instant claim 37) in the subject to form a surface map (see claim 10 of Bhatia) and that the scanning is done using a laser, electron beam, magnetic resonance imaging, microwave, x-ray, or computed tomography (see claim 11 of Bhatia) (“wherein the scanning . . . is achieved using a laser, electron beam, magnetic resonance imaging, microwave, x-ray, computed tomography” as in instant claim 38). The resulting surface map can then be used to guide the deposition of cells (p. 10, para 0043). This reference shows that a surface map can be created by scanning a desired surface using laser, electron beam, magnetic resonance imaging, microwave, x-ray, or computed tomography. Therefore, it would have been obvious to dedifferentiate fibroblasts into induced pluripotent stem cells to be used in a 3D bioprinting process, as taught by Yamanaka, using the 3D inject bioprinter of Boland and arrive at the instantly claimed invention. One of ordinary skill would have been motivated to use this inkjet bioprinter to print the resulting induced pluripotent stem cells because it is relatively inexpensive, quick, and efficient in depositing arrays of viable cells, including adult derived cells of the skin. It also would have been obvious to use dedifferentiated fibroblasts in a 3D bioprinting process, as taught by Yamanaka and Boland in combination, using the 3D printer taught by Boland, with a surface map of a desired organ created by scanning using a laser, electron beam, magnetic resonance imaging, microwave, x-ray, or computed tomography, as taught Bhatia, to arrive at the instantly claimed invention. One of ordinary skill in the art would be motivated to make this combination because the generated surface map guides the deposition of the cells to be used in the bioprinting process. Response to Arguments Applicant did not provide any arguments or challenge the specific teachings of previously cited reference Boland or Bhatia. Claim(s) 1, 10, 12-13, 16, and 43- 44 is/are rejected under 35 U.S.C. 103 as being unpatentable Yamanaka in view of Taranger et al (Mol Biol Cell. 2005 Dec; 16(12):5719-35. Epub 2005 Sep 29). Yamanaka differ from the instant invention in that it does not teach fibroblasts are transfected with cytoplasm derived from stem cells in order to induce dedifferentiation (claim 10), wherein the cytoplasm derived from stem cells is from pluripotent stem cells (instant claim 12), that the suitable conditions for dedifferentiation do not include transcription factors. However, before the effective filing date of the instant invention, Taranger teaches functional reprogramming of a differentiated cell toward pluripotency (abstract). It tests the hypothesis that an extract of undifferentiated somatic cells can elicit dedifferentiation in a somatic cell line. Based on morphological and immunolabeling observations, gene expression profiling, DNA methylation assays, and functional assessments, we show that 293T and NIH3T3 cells can be programmed by extracts of undifferentiated NCCIT cells or mouse ES cells to acquire characteristics of pluripotency (Introduction para 4). ES cell extract promoted Oct4 transcription in fibroblasts (Results; “wherein said fibroblasts are transfected with cytoplasm derived from stem cells in order to induce dedifferentiation” as in instant claim 10; “wherein the cytoplasm derived from stem cells is from pluripotent stem cells” as in instant claim 12; “wherein the suitable conditions for dedifferentiation do not include transcription factors” as in instant claim 43; “wherein the suitable conditions do not include OCT-4” as in instant claim 44). Within 4–9 d after ESC extract treatment, a proportion 3T3 cells formed distinct colonies of small round cells that lifted from the surface to form embryoid-like bodies (aggregate culture) (“wherein the fibroblasts are cultured as a plurality of cell aggregates” as in instant claim 16). Embryoid-like bodies derived from ESC extract-treated cells expressed ALP, another embryonic and ESC marker, after 8 d of culture (Figure 9, C and D; 1 wk after extract exposure; “wherein said dedifferentiated fibroblasts additionally express detectable levels of one or more genes selected from the group consisting of alkaline phosphatase (ALP)” as in instant claim 13). This shows that fibroblasts can be effectively reprogrammed without use of transcription factors. Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to dedifferentiate fibroblasts into induced pluripotent stem cells in the presence of valproic acid and hypoxia as taught by Yamanaka and Bhatia in combination, where the culture does not include transcription factors and does not include OCT-4 as taught by Taranger, to arrive at the instantly claimed invention. Taranger shows fibroblasts can be reprogramed via exposure to embryonic stem cell extract, one of ordinary skill would have been motivated to simply substitute one known element (transcription factors of Yamanaka) for another (stem cell extract of Taranger) to obtain the predictable result of advantageously producing induced pluripotent stem cells as taught by the prior art. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN C REGLAS whose telephone number is (571)270-0320. The examiner can normally be reached M-F 7-3. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras Jr can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /G.R./Examiner, Art Unit 1632 /KARA D JOHNSON/Primary Examiner, Art Unit 1632
Read full office action

Prosecution Timeline

Dec 11, 2020
Application Filed
Oct 06, 2023
Non-Final Rejection — §103, §112
Mar 06, 2024
Response Filed
Mar 15, 2024
Final Rejection — §103, §112
Sep 19, 2024
Request for Continued Examination
Sep 23, 2024
Response after Non-Final Action
Nov 01, 2024
Non-Final Rejection — §103, §112
May 06, 2025
Response Filed
Jul 22, 2025
Final Rejection — §103, §112
Jan 28, 2026
Request for Continued Examination
Jan 30, 2026
Response after Non-Final Action
Mar 19, 2026
Non-Final Rejection — §103, §112 (current)

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Prosecution Projections

5-6
Expected OA Rounds
25%
Grant Probability
86%
With Interview (+60.6%)
3y 5m
Median Time to Grant
High
PTA Risk
Based on 48 resolved cases by this examiner. Grant probability derived from career allow rate.

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