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 .
Withdrawn Rejections
The rejection of claims 4 and 8 under 35 USC 112(d) is withdrawn. These claims have been canceled rendering their rejection moot.
The rejections under 35 USC 103 are withdrawn. The amendments to the claims take limitations from 4 different dependent claims, previously under consideration but now canceled, and incorporate them into independent claim 1. The previous dependent claims were each independently dependent upon base claim 1 in the previously round of prosecution and therefore span across different 103 rejections. As such, new 103 rejection need to be configured to consider the amendments under consideration.
The rejection of claim(s) 1, 3-6, 8-10, 12-14, 17, 19, 22, and 24, under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (Zhang et al. Circ Heart Fail. 2015;8:156-166), is withdrawn. The amendments to the claims are not disclosed by Zhang. Zhang is still an applicable prior art that could have been used in a 103 rejection. However, given time is limited for examination and the newly made rejections sufficient teach the claims an addition set of 103 rejections was not made.
The following new rejections are necessitated by the amendments to the claims:
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 5-6 and 8 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 5 depends upon claim 4. However, the amendments to the claims cancel claim 4. As such, it is not apparent from which claim claim 5 should de depend.
Claims 5 and 8 are dependent upon claim 5 and therefore are also indefinite as dependent upon a canceled claim. For purposes of applying applicable art, claim 5 will be interpreted as dependent upon claim 1.
Claim Interpretation
The claims generally comprise idiomatic language that appears to be a translation. An indefiniteness rejection under 35 USC 112b was considered but not applied because Examiner believes that an ordinary artisan can decipher the intended meets and bound of the claims.
Claim 1, as amended, is a method of manufacturing viable autologous cardiac linages cells that has five generic active steps that are further described by wherein clauses that recite multiple more specific steps to arrive the five active steps.
For purposes of identifying applicable art the five step will be interpreted as such:
The “receiving” step, hereafter (i), will be interpreted as obtaining a skin biopsy sample from a patient. The “producing” step, hereafter (ii), will be interpreted as transferring the sample to a first growth media to obtain a plurality of fibroblasts; and reprogramming the plurality of fibroblasts in an iPSC reprogramming media to produce a plurality of confluent iPSC. The “identifying” step, hereafter (iii), will be interpreted as subjecting the confluent plurality of iPSC to an etoposide sensitivity test and automated image capture to identity a plurality of viable iPSC. The “differentiating” step, hereafter (iv), will be interpreted as subjecting the plurality of viable iPSC to 2D culture then 3D culture in the presence of ECM to produce a plurality of viable cardiac linage cells and washing the plurality of cardiac linage cells with DPBS with Ca and Mg. The “separating” step, hereafter (v), will be interpreted as dissociating the plurality of viable cardiac lineage cells into a single cell suspension.
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.
(1) Claim(s) 1, 3, 5-6, 8, 10, 12-14, and 19 are under 35 U.S.C. 103 as being unpatentable over Pedersen et al., 2016 (WO 2016/009196 A1) in view of Khan et al., 2021 WO 2021/247844 A1), Kim, Kwang-Soo, 2020 (WO 2020/237104 A1), Bai et al., 2018 (J. Vis. Exp. (138), e58252, p. 1-6), Secreto et al., 2017 (Stem Cells Translational Medicine, 6: 1829-1839), and Maddah et al, 2014 (Journal of Laboratory Automation 19(5):454-460).
Regarding claim 1, Pedersen teaches the reprogramming method of the (iii) and the 2D expansion process of iPSC of the (iv) of claim 1 by teaching a method for the production of autologous cardiac lineage cells from iPSC (abstract). iPSCs are pluripotent stem cells derived from ancestor cells including somatic cells, such as adult fibroblasts and peripheral blood cells. Ancestor cells are typically reprogrammed by the introduction of pluripotency genes or proteins, such as Oct4, Sox2, KLF4 and c-Myc into the cells. The genes may be introduced into the differentiated cells via plasmid or viral transfection. Other genes such as L-Myc and N-Myc may also be introduced into the cell to increase induction efficiency. Following introduction of the pluripotency genes, the ancestor cells may be cultured (i.e. transferring fibroblast into a reprogramming medium as claimed) and cells expressing pluripotency markers may be isolated and purified to produce a population of iPSCs (e.g. p. 5, last paragraph) (For claims 4-5 and 9-10). The pluripotent stem cells preferably are human iPSCs and the iPSCs may be derived from fibroblasts. iPSCs may be obtained from an individual to produce autologous mesodermal cells, such as cardiomyocytes or chondrocytes (e.g. p. 6 lines 4-15). Pluripotent stem cells may be grown in defined conditions or cultured on a culture dish on a layer of feeder cells (i.e. 2D expansion process of confluent iPSC as claimed). Suitable culture media for pluripotent stem cells include KO-DMEM supplemented with 20% serum replacement and DMEM/F12 supplemented with 20% knockout serum replacement (KSR) (e.g. bridging p. 6, last line to p. 7, 2nd paragraph). Anterior PS-like cells are suitable for differentiation into mesoderm cells of the cardiac lineage, such as cardiac mesoderm, cardiomyocyte progenitors and cardiomyocytes (e.g. p. 10, 2nd paragraph). Pedersen teaches pluripotent stem cells may be substantially free from one or more other cell types and the pluripotent stem cells may be separated from other cell types by using technique based on the recognition of extracellular epitopes by antibodies and magnetic beads or fluorescence activated cell sorting (MACS or FACS) including use of antibody against SSEA4 (e.g. p. 7, 4th paragraph).
Pendersen does not teach performing 3D expansion in ECM on the 2D iPSC cells. However, Khan teaches preparing a PCL-gelatin scaffold for 3D culture were coated with Matrigel (i.e. a 3D extracellular matrix that provides a biomimetic environment). Khan teaches human iPSCs cultured in 2D culture plates were dissociated into single cells by incubating with Gentle Cell Dissociation reagent in E8 medium supplemented with ROCK inhibitor to get a concentrated cell suspension, which was added dropwise onto individual 3D plates (0.2 million cells per 12mm patch) (e.g. p. 21, lines 25-33) (For claim 1). Cardiac differentiation of hiPSCs was performed using a Cardiomyocyte Differentiation Kit. The medium for cultures was changed every other day. The morphological changes during cardiac differentiation of ihPSCs were assessed by phase-contrast imaging using a Leica DM IL LED microscope. Videos were recorded to monitor the contractility of functional cardiomyocytes and quantitative analysis was performed post-acquisition. The beating frequencies of differentiated cardiomyocytes were manually counted (e.g. p. 22, lines 4-16) (For claim 19). Immunofluorescence imaging was performed on undifferentiated and differentiated cells cultured on 3D patches and on coverslips (2D). The cultured cells were washed twice with DPBS and processed for immunostaining (e.g. p. 23, lines 2-4) Thus, Khan teaches washing the plurality of cardiac lineage cells with DPBS as claimed. Khan teaches the use of scaffold/extracellular matrix is currently being investigated to improve the survival of stem cells and to provide trophic support to the ischemic heart (e.g. p. 29, lines 30-32) (For claim 3). Using hiPSC-derived cells can allow for autologous cell transplantation and an electrospun co-axial nanofiber scaffold can lend structural support to the ventricle (e.g. p. 32, lines 10-12).
It would have been obvious to an artisan of ordinary skill before the effective filing date to apply the 3D differentiation method of Khan to the reprogramming method (iii) and 2D expansion method of (iv) to predictably arrive at the full limitations of step (iv). An artisan would have a reasonable expectation of success because Pendersen successfully reprograms fibroblast to iPSC and successfully expands in 2D culture. Further, Pendersen teaches that iPSC derived by their method and expanded in 2D culture can successfully be differentiated into cardiac lineage cells. Further Khan also successfully uses 2D expansion in their method of differentiating iPSC into cardiac linage cells and further successfully uses the 2D expansion process in a 3D ECM differentiation process to successfully arrive at cardiac linage cells. As such, Khan provides an obvious variant of the differentiation method of Pendersen. Further an artisan would be motivated to use the 3D process of Khan in the method of Pendersen because Khan teaches the 3D scaffold comprising an extracellular improves the survival of the iPSCs thus improving the survival rate of end-product cardiac linage cells.
While Pendersen teaches the use of fibroblast as the starting cell type for producing iPSC, Pendersen does not teach that a skin biopsy is taken to receive a patient specific sample as recited in (i) of the claims and that a plurality of fibroblast are obtained from the biopsy for the reprogramming to iPSC as recite in (ii) of the claims. However, Kim teaches fibroblasts harvested from a skin biopsy were used to generate multiple iPSC lines that were tested for pluripotent differentiation potential in vitro and in vivo and screened for somatic mutations using whole exome sequencing (e.g. p. 73, lines 15-18).
Thus it would have been obvious to an artisan of ordinary skill in the art before the time of effective filing to obtain fibroblasts from a dermal biopsy for reprogramming, as taught by Kim, for use in the method of Pendersen to predictably arrive at the limitations of step (i) and (ii) as claimed. One would have a reasonable expectation of success because Kim demonstrates that fibroblast can successfully be obtained from skin biopsies and can successfully be reprogrammed. Further, one of ordinary skill would be motivated to use fibroblast obtained from a skin biopsy because it is well established in the prior art that skin biopsy is one of the least invasive means of obtaining fibroblast cells due to its superficial nature in the body structure. As such, Pendersen in view of Khan and Kim teach obvious variants of steps (i)-(iv) as claimed.
Pendersen in view of Khan does not teach further separating the plurality of cardiac lineage cell as claimed in (v). However, Bai teaches “a novel and easy net mold-based method to create three-dimensional (3-D) cardiac tissues without additional scaffold material. Human-induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs), human cardiac fibroblasts (HCFs), and human umbilical vein endothelial cells (HUVECs) are isolated and used to generate a cell suspension with 70% iPSC-CMs, 15% HCFs, and 15% HUVECs. They are co-cultured in an ultra-low attachment "hanging drop" system, which contains micropores for condensing hundreds of spheroids at one time. The cells aggregate and spontaneously form beating spheroids after 3 days of co-culture. The spheroids are harvested, seeded into a novel mold cavity, and cultured on a shaker in the incubator. The spheroids become a mature functional tissue approximately 7 days after seeding. The resultant multilayered tissues consist of fused spheroids with satisfactory structural integrity and synchronous beating behavior. This new method has promising potential as a reproducible and cost-effective method to create engineered tissues for the treatment of heart failure in the future” (e.g., Abstract). hiPSCs were differentiated into hiPSC-CMs and at 16-18 days post-differentiation, suspend cardiomyocytes by rinsing each well with 2 ml of 1XPBS, followed by incubation with 1 ml/well of trypsin or cell dissociation reagent. Neutralize the trypsin or cell dissociation reagent with an equal volume of RPME cell media supplemented with B-27, collect the suspended cardiomyocytes, centrifuge the cell suspension to obtain a cell pellet and resuspend the pellet in 10 ml of RPMI/B-27 cell media (e.g., p. 1-2, steps 1-7 under “Preparation of Cardiomyocytes”).
As such, it would have been obvious to an artisan of ordinary skill before the time of effectively filing to further separate the cardiac linage cells produced as described in Pendersen in view of Khan using the dissociation and single cell suspension method described by Bai to predictable arrive at the limitations of step (v). An artisan would have a reasonable expectation of success because Bai demonstrates that cardiac linage cells differentiated in 3D culture can be successfully dissociated and separated as claimed. Further, an artisan would be motivated to additional do a dissociation step as described by Bai because Bai teaches it will arrive at a single cell suspension of cardiomyocytes to build further 3D cardiac tissues.
Pendersen does not teach that the obtained plurality of iPSCs are subjected to an etoposide sensitivity test and automated image capturing that can be used to select iPSC as recited in (iii).
However before the time of effective filing, Secreto teaches “human induced pluripotent stem cells (hiPSC) hold great promise in diagnostic and therapeutic application. However, translation of hiPSC technology depends upon a means of assessing hiPSC quality that is quantitative, high-throughput, and can decipher malignant teratocarcinoma clones from normal cell lines”. Secreto describes a novel method for determining hiPSC quality that exploits pluripotent cell’s documented hypersensitivity to the topoisomerase inhibitor etoposide. A half maximal effective concentration of <300 nM following 24 hours of exposure to etoposide demonstrated a positive correlation with RNA profiles and colony morphology metrics associated with high quality hiPSC clones. The etoposide sensitivity assay (ESA) provides a simple, straightforward method to establish hiPSC quality in a quantitative and functional assay capable of being incorporated into a generalized method for establishing a quality control standard for all types of pluripotent stem cells (E.g., Abstract).
Maddah teaches due to the rapid adoption and use of human induced pluripotent stem cells (iPSCs) in recent years, there is a need for new technologies that standardize the evaluation of iPSCs to allow the objective comparison of results across different experiments and groups. We present a noninvasive, fully automated, and analytical system for morphology based evaluation of iPSC cultures that consists of time-lapse microscopy and novel image analysis software. The presented system acquires low-light phase-contrast images of iPSC growth collected during a period of several days in culture, measures geometrical- and texture-based features of iPSC colonies throughout time, and derives a set of six biologically relevant features to automatically rank the quality of the cell culture. In a study of 94 iPSC cultures, we demonstrated the accuracy of the system by comparing the automated ranking with an independent expert evaluation based on visual review of the time-lapse movies (see abstract).
As such, it would have been obvious to an artisan of ordinary skill before the time of effective filing further add an etoposide sensitivity test as taught by Secreto and automated image capturing taught by Maddah to the method of producing iPSC taught by Pendersen in further view of Kahn, Bai to predictably arrive at the limitations of (iii) of the claim. An artisan would have a reasonable expectation of success in applying the etoposide sensitive test to the iPSC produced in Pendersen because Secreto teaches the method is simple and straightforward to apply to iPSC. An artisan would also have a reasonable expectation of success in applying the automated image capturing to the iPSC of Pendersen because Maddah teaches their automated imagine system accurately identifies high quality thus viable iPSC. As such, Pendersen in view of Kahn, Bai, Secreto, and Maddah teaches, thus renders obvious all the limitations of claim 1.
Regarding claim 3, Pendersen does not teach transferring iPSC a vessel comprising ECM matrix. However, Khan teaches iPSC 3D culture comprising ECM in a vessel as discussed above.
Regarding claim 5, Pendersen teaches introducing reprogramming factors as polynucleotides via a viral vector as discussed above.
Regarding claim 6, Pendersen teaches polynucleotides that are RNA as discussed above.
Regarding claim 8, Pendersen teaches that the polynucleotide can be delivered via a viral vector. However, Pendersen does not teach that the viral vector is a Sendai viral vector. However, Kim suggests the same combination using alternative delivery methods, such as mature mRNA/miRNA or Sendai virus (e.g. p. 18, lines 8-23, p. 55, line 11). The 299 hiPSC lines generated by Sendai virus method showed significantly less mutations than hESC lines. The hiPSC lines carried smaller number of mutations in genes frequently mutated in cancer (e.g. p. 59, line 21, to p. 60, line 4).
As such, it would have been obvious to an artisan of ordinary skill before the time of effectively filing to use the Sendai viral vector, as taught by Kim, as the viral vector encoding the reprogramming factor taught by Pendersen in the claimed method to predictably arrive at the limitations of claim 8. The artisan would have a reasonable expectation of success because Kim taches is a success means of transducing and reprogramming fibroblast. Further the artisan would be motivated to do so because Kim teaches the 299 hiPSC lines generated by Sendai virus method showed significantly less mutations than hESC lines and the hiPSC lines carried smaller number of mutations in genes frequently mutated in cancer.
Regarding claim 10, Pendersen teaches 2D expanding of iPSC as discussed above.
Regarding claims 12-13, Pedersen teaches the anterior PS induction medium may be chemically defined nutrient medium comprising chemically defined basal medium supplemented with one or more additional defined components. The chemically defined basal media includes IMDM, DMEM and RPMI 1640 (e.g. p. 8, 1st paragraph). The chemically defined basal medium apparently has optimized serum-free supplement.
Regarding claim 14, Pedersen teaches the population of anterior PS-like cells can be further differentiated into cardiac mesoderm cells by culturing the cells in cardiac mesoderm induction medium comprising FGF, BMP, a wnt signaling inhibitor and retinoic acid to produce a population of cardiac mesoderm cells (e.g. p. 10, 3rd paragraph). Suitable Wnt inhibitor includes IWP2 (e.g. p. 10, 3rd to last paragraph).
Regarding claim 19, Pedersen teaches cardiomyocytes produced may have one or more functional properties of cardiomyocytes including the formation of beating cellular clusters or sheets, active Ca2+ signaling and the generation of action potential. Cardiomyocyte function may be determined in the cardiomyocyte populations by conventional techniques, such as Ca2+ imaging and path clamp electrophysiology (e.g. p. 12, 9th and 10th paragraphs).
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A, B, and G are applicable. The claimed method was known in the art at the time of filing as indicated by Pendersen in view of Kahn, Bai, Secreto, and Maddah. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
(2) Claim(s) 1, 12, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Pedersen et al., 2016 (WO 2016/009196 A1) in view of Khan et al., 2021 WO 2021/247844 A1), Kim, Kwang-Soo, 2020 (WO 2020/237104 A1), Bai et al., 2018 (J. Vis. Exp. (138), e58252, p. 1-6), Secreto et al., 2017 (Stem Cells Translational Medicine, 6: 1829-1839) and Maddah et al 2014 (Journal of Laboratory Automation 19(5):454-460), as applied to claims 1, 3, 5-6, 8, 10, 12-14, and 19 above, and further in view of Matinez Fraiz et al., 2019 (US 20190365951 A1).
Claims 1, 12, 14 and 16 are directed to a method of manufacturing autologous cardiac lineage cells, the method comprises receiving a patient-specific sample from a subject, producing a plurality of fibroblast cells as a function of the patient-specific sample, wherein producing the plurality of fibroblast cells comprises transferring the patient-specific sample to a first growth media; generating a plurality of induced pluripotent stem cells (iPSCs) as a function of the plurality of fibroblast cells, wherein generating the plurality of iPSCs comprises identifying a plurality of confluent iPSCs from the plurality of iPSCs, wherein identifying the plurality of confluent iPSCs from the plurality of iPSCs comprises subjecting each iPSC of the plurality of iPSCs to a quality test, wherein the quality test is an etoposide sensitivity test, and selecting a confluent iPSC as a function of the quality test, and differentiating the iPSCs into a plurality of cardiac lineage cells comprising cardiomyocytes, wherein differentiating the iPSCs into cardiac lineage cells comprises performing a two-dimensional (2D) expansion process on the plurality of confluent iPSCs, performing a three-dimensional (3D) expansion process on the 2D expanded plurality of confluent iPSCs, differentiating the 3D-expanded plurality of confluent iPSCs into autologous cardiac lineage cells, and separating the plurality of cardiac lineage cells into a plurality of discrete cellular objects using a dissociation process, wherein the dissociation process creates a single-cell suspension from the discrete cellular objects. Claim 12 specifies differentiating the plurality of iPSCs into cardiac lineage cells comprises transferring the confluent iPSCs to a differentiation media. Claim 14 specifies transferring the plurality of confluent iPSCs to a differentiation media comprises adding a supplementary media into the differentiation media, wherein the supplementary media is configured to modulate a Wnt signaling pathway. Claim 16 specifies the supplementary media comprises an inhibitor containing IWP4.
The teachings of Pedersen, Khan, Bai and Secreto are as discussed above. Pedersen, Khan, Bai and Secreto do not specifically teach the supplementary media comprises an inhibitor containing IWP4.
Martinez Fraiz teaches a method for producing a human tridimensional macroscale cardiac construct by differentiating human pluripotent stem cells (hPSCs) into contracting cardiomyocytes, suspending the contracting cardiomyocytes together with human fibroblasts to obtain a mixed cell suspension, seeding the mixed cell suspension into a collagen-based porous scaffold to obtained a seeded scaffold, and transferring the seeded scaffold to a bioreactor and culturing the seeded scaffold under perfusion with electrical stimulation for cardiomyocyte maturation to obtain a human tridimensional macroscale cardiac construct (e.g. claim 1). iPScs may be used in the method of the disclosure and the iPSCs can be derived from human foreskin dermal fibroblasts (e.g. [0045]). Cardiomyocyte differentiation is conducted in monolayer culture with a method comprising the addition of a GSK3 inhibitor, such as CHIR99021, followed by the addition of a Wnt signaling inhibitor, such as IWP4, generally at day 3 of the differentiation. Spontaneously contracting cardiomyocytes are obtained at around day 8 (e.g. [0048]).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to culture the plurality of confluent iPSCs in a differentiation medium supplemented with a supplementary media configured to modulate a Wnt signaling pathway, such as IWP4, because Pedersen teaches the population of anterior PS-like cells can be further differentiated into cardiac mesoderm cells by culturing the cells in cardiac mesoderm induction medium comprising FGF, BMP, a wnt signaling inhibitor, such as IWP2, and retinoic acid to produce a population of cardiac mesoderm cells, and Martinez Fraiz teaches differentiation of hESC or iPSC into contracting cardiomyocyte and cardiomyocyte differentiation is conducted in monolayer culture with a method comprising the addition of a GSK3 inhibitor, such as CHIR99021, followed by the addition of a Wnt signaling inhibitor, such as IWP4. Both Pedersen and Martinez Fraiz teach differentiation of iPSCs into cardiomyocytes. Since Pedersen teaches using a wnt signaling inhibitor such as IWP2 and Martinez Fraiz teaches using culture medium comprising a Wnt signaling inhibitor such as IWP4 during the cardiomyocyte differentiation, it would be obvious for one of ordinary skill in the art to culture the plurality of confluent iPSCs in a differentiation medium supplemented with a supplementary media comprising a Wnt signaling inhibitor such as IWP4 in order to optimize the efficiency of reprogramming iPSCs or PSCs into cardiomyocytes with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to produce autologous cardiac lineage cells from iPSCs generated from fibroblast cells that is obtained from an individual as taught by Pedersen or to produce a human tridimensional macroscale cardiac construct by differentiating human pluripotent stem cells (hPSCs) into contracting cardiomyocytes, suspending the contracting cardiomyocytes together with human fibroblasts to obtain a mixed cell suspension, and seeding the mixed cell suspension into a collagen-based porous scaffold as taught by Martinez Fraiz with reasonable expectation of success.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632