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 .
DETAILED ACTION
The instant application is in response to the papers filed on June 21, 2023. Pursuant to the amendment filed on June 21, 2023, claims 1-4 and 22-33 are currently pending of which claims 4, 26-29 have been amended, claims 5-21 have been cancelled, and claims 30-33 are newly filed.
Therefore, claims 1-4, and 22-33 are currently under examination to which the following grounds of rejection are applicable.
Priority
This application claims benefit to provisional application No. 63/141,626, filed on January 26, 2021, in a language other than English. An English translation of the non-English language provisional application and a statement that the translation is accurate must be filed in provisional application No. 63/141,626. See 37 CFR 1.78. The English translation and a statement that the translation is accurate required by 37 CFR 1.78 is missing. Accordingly, applicant must supply 1) the missing English translation and a statement that the translation is accurate in provisional application No. 63/141,626 and 2) in the present application, a confirmation that the translation and statement were filed in the provisional application. If 1) and 2) are not filed (or if the benefit claim is not withdrawn) prior to the expiration of the time period set in this Office action, the present application will be abandoned. See 37 CFR 1.78.
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/JP2022/001814, filed January 19, 2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 21, 2023 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because Figure 2 fails to properly depict labels for the three lanes in Fig. 2, specifically the figure only recites “Conventional Example” twice and the last lane as “Example.” However, there is no further information provided in the Specification in relation to these labels, nor additional information pertaining to these samples.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 1-3, 22, 24-26, and 30 are objected to because the recited abbreviations, “OLIG”, “SOX”, “NKX”, “iPS”, “ES”, and “ASCL”should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 4, 22-27, 30-31 are rejected under 35 U.S.C. 102(a)(1)(2) as being anticipated by Vallier et al . (US 2019/0338309 A1).
Regarding claim 1, Vallier teaches a method of producing oligodendrocytes from pluripotent stem cells, said method comprising the steps of: a) the targeted insertion of a gene encoding a transcriptional regulator protein into a first genetic safe harbor site of human somatic cells or human pluripotent stem cells; and b) the targeted insertion of any combination of the SOX 10, OLIG2, NKX2.2, and NKX6.2 genes that are operably linked to an inducible promoter into a second genetic safe harbor site, wherein said inducible promoter is regulated by a transcription regulatory protein (claims; paragraph par 69-72). Moreover, Example 4 states that an OLIG2 gene and a SOX2 gene in form of a bicistronic expression cassette were inserted into human pluripotent stem cells, and that double-overexpressing cells were induced in oligodendrocytes (figure 12).
Regarding claim 2, dependent on claim 1, the rejection to claim 1 is applied herein, wherein Vallier teaches inducers comprise OLIG, NKX, and SOX (“the production of oligodendrocytes from pluripotent stem cells, comprising the steps of:…targeted insertion of any combination of the SOX 10, OLIG2, NKX2.2, AND NKX6.2 genes” (par 69-71).
Regarding claim 4, dependent on claim 1, Vallier teaches wherein the inducers further comprise a factor that promotes cell proliferation (“Additional genes including certain members of the Klf family, the Myc family, Nanog, and LIN28, may increase the induction efficiency. Examples of the genes which may be contained in the reprogramming factors … c-Myc…, and these reprogramming factors may be used singly, or in combination of two or more kinds thereof.” (par 201); “For the treatment of solid tumours , genes encoding toxic peptides … , tumour suppressor genes such as p53 , genes coding for mRNA sequences which are antisense to transforming oncogenes , … may be expressed.” (par 231). The instant Specification describes these genes/proteins in relation to cell proliferation “ In the methods for producing oligodendrocytes and progenitor cells thereof, the factor that promotes cell proliferation may be at least one selected from the group consisting of a factor that suppresses p53 gene, a factor that suppresses Rb gene, and MYC. MYC may be c-MYC.” (par 0008).
Regarding claims 22-27, 30-31, which are directed to the directed to the reprogramming of somatic cells using the same inducers as described in the aforementioned claims, e.g. OLIG, SOX, ASCL, and NKX, Vallier teaches the cells can be mature somatic cells, comprising blood cells (par 0225-0227).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The 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.
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 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Vallier et al . (US 2019/0338309 A1) as applied to claim 1 above, and further in view of Sugimori et al. (Development 1 April 2008; 135 (7): 1271–1281).
Regarding claim 4, the disclosure of Vallier is applied as in the 102 rejections above, the content of which is incorporated above, in its entirety.
Regarding claim 3, dependent on claim 1, Vallier teaches select enhancers, e.g. SOX10, OLIG2, and NKX2.2, to be overexpressed in pluripotent stem cells for the production of oligodendrocytes (par 0069-71).
Vallier does not teach these enhancers as further including ASCL1.
Sugimori teaches Ascl1 is involved in terminal differentiation of oligodendrocytes late in development, the co-expression of Olig2 and Nkx2-2 in oligodendrocyte progenitors (OLPs) are impaired in Ascl1–/– mutants, and furthermore, gain-of-function studies showed that Ascl1 collaborates with Olig2 and Nkx2-2 in promoting differentiation of OLPs into oligodendrocytes in vitro, in which the overexpression of Ascl1, Olig2 and Nkx2-2 alone stimulated the specification of OLPs, but the combinatorial action of Ascl1 and Olig2 or Nkx2-2 was required for further promoting their differentiation into oligodendrocytes. The studies determined Ascl1 regulates multiple aspects of oligodendrocyte development in the spinal cord (abstract).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the inducers to promote differentiation of stem cells to oligodendrocytes as taught by Vallier to incorporate ASCL1 as taught by Sugimore because it would have been obvious to combine prior art elements according to known methods to yield predictable results, wherein the result is successful differentiation of pluripotent stem cells to oligodendrocytes. The inclusion of ASCL1 for the differentiation of pluripotent stem cells as described Sugimori would have led to predictable results with a reasonable expectation of success because Sugimori clearly describes that the ASCL1 is connected with Olig2 and Nkx2-2 in promoting differentiation of OLPs into oligodendrocytes, and therefore the use of all the claimed inducers are likely to produce oligodendrocytes.
Claims 22, 24, 28-29, 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Vallier et al . (US 2019/0338309 A1) as applied to claims 22 and 24 above, and further in view of Yamanaka et al. (US 8,048,999 B2) and Wang et al. (Proceedings of the National Academy of Sciences 111.28 (2014): E2885-E2894).
Regarding claims 22 and 24, the disclosure of Vallier is applied as in the 102 rejections above, the content of which is incorporated above, in its entirety.
Regarding claims 28-29, 32-33, that are directed to the reprogramming of somatic cells to oligodendrocytes with the claimed inducers rejected above for claims 22 and 24, Vallier teaches somatic cells can be differentiated oligodendrocytes, but does not teach these somatic cells as including fibroblasts or mononuclear cells.
Yamanaka teaches the reprogramming of somatic cells by the transfection of Oct4, Sox2, Klf4, or c-Myc as a means for inducing reprogramming of a differentiated cell (abstract; col 2, ln 28-40). The somatic cells include fibroblasts as seen in Examples 4 and 9, and the produced induced pluripotent stem cells were capable of differentiation into oligodendrocytes (Fig. 20, Example 8). Altogether, Yamanaka teaches “In the preparation of induced pluripotent stem cells by using the nuclear reprogramming factor of the present invention, types of somatic cells to be reprogrammed are not particularly limited, and any kinds of somatic cells may be used.”
In reference to directly differentiation somatic cells without a step of reprogramming into iPSs, Wang teaches “Somatic cell reprogramming through various combinations of TF overexpression has been established as a novel means to induce transdifferentiation of various somatic cell types, typically fibroblasts, to neuronal and other lineages (39). Two recent studies have demonstrated this approach with rodent fibroblasts and induction of OPC-like and oligodendrocyte fate using a combination of Sox10, Olig2, and either Zfp546 or Nkx6.2” (p E2892, col 2).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the invention to use the claimed inducers that have been shown to commit stem cell fates to oligodendrocytes as taught by Vallier on somatic cells or reprogrammed somatic cells, because Yamanaka teaches successful reprogramming of various somatic cells to iPSs with select TF factors (known in the art as “Yamanaka factors”), and therefore subsequent use of the claimed inducers would likely lead to the differentiation of oligodendrocytes as has been shown by Vallier on induced pluripotent stem cells (Vallier claim 19). Moreover, in reference to transdifferentiation of a somatic cells to another somatic cells, Wang clearly teaches this with the claimed inducers on fibroblasts to oligodendrocytes. In summary, it would have been obvious to try in using these claimed inducers on somatic cells and/or stem cells as the person of ordinary skill would be choosing from a finite number of identified, predictable solutions with a reasonable expectation of success.
Conclusion
Claims 1-4, and 22-33 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634