CTNF 18/332,209 CTNF 88611 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions 08-06 AIA Claim s 8 and 9 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/10/2025 . Priority Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan on 6/14/2022 (and 11/8/2022; and 3/1/2023). It is noted, however, that applicant has not filed a certified copy of the JP 2022/095627 (and JP 2022/178783; and JP 2023/030877 [respectively]) application as required by 37 CFR 1.55. The Applicant has only provided “interim copies,” and has not included any certified copies of the foreign priority documents. Specification 07-29-04 The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See paragraph [0070]. 06-19 AIA The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g). Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claim 7 is 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 7 is indefinite because it lacks both a preamble and a transitional phrase. With respect to the former, the lack of preamble makes it unclear what statutory category the claim belongs in; although it would be reasonable to assume that the claim is a composition, this is not clear from the claim language. See MPEP 2111.02. Additionally, by not including a transitional phrase, there is no reasonable manner to determine the metes and bounds of the claimed “stage 5 neurons.” See MPEP 2111.03. For example, it is unclear if the claim is limited to the cells (consisting of), or if compositions that include other ingredients can be considered (comprising). Claim 7 is further indefinite because it is unclear if the limitation “… and cultured in a container” is meant to provide a product-by-process limitation (see MPEP 2113), or if the claim is limited to the cells and a culture container. For the sake of examining the claim on its merit, it will be assumed that the limitation is meant to be interpreted as a product-by-process limitation. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claim 7 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) isolated stage 5 neurons, in culture. This judicial exception is not integrated into a practical application because the claim provides for an isolated naturally occurring cell and nothing more. See MPEP 2106.04(b)(II) and 2106.04(c). The claim is drawn to a cell, per se , wherein the claimed cell is described as isolated . Based upon the claim language, the claim is drawn to a naturally occurring isolated neuron, with mature dendrites. Since stage 5 neurons, with mature dendrites, exist in nature, the claim as a whole must be considered a product of nature. See Dotti, et al ( The Journal of Neuroscience , 8, 1454-1468, 1988), page 1461-1464, “Morphological stages in the establishment of axonal and dendritic domains” section. Since it is established that the cell, per se , is naturally occurring, one must also consider the acts of isolating and culturing the claimed cell. Based upon Office guidance regarding Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014), the act of isolating and culturing do not impart anything to the naturally occurring cell, and as such, do not make the claimed cell eligible under 35 USC 101. See MPEP 2106.04(b)(II). Furthermore, since these elements do not impart any different features to the naturally occurring cell, there are no markedly different characteristics that must be analyzed. See MPEP 2106.04(c). Claim Rejections - 35 USC § 102/103 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-27-aia AIA Claim s 1-4 and 7 are rejected under 35 U.S.C. 102( a)(1 ) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lesuisse, et al ( Journal of neurobiology , 5, 9-23, 2002) and Kaech, et al ( Nature Protocols , 1, 2506-2415, 2006). Lesuisse teaches methods of culturing neurons in a culture media containing B27, wherein Lesuisse indicates that the neurons matured , and developed dendrites. See page 9, “Abstract” section. Lesuisse teaches all of the claimed steps, but does not state what stage the cultured neurons on at. Lesuisse appears to teach cells that are at stage 3, by indicating the positivity for MAP2, and explicitly indicates a maturation of the cell and dendrites. See page 13, “Immunocytochemical Characterization of Cortical Motor Neuron Cultures” section; page 14, Figure 3; page 15, Figure 4; page 16, left column; page 18, left column, 1 st [full] paragraph. As such, although Lesuisse does not state the stage of development of the neurons, it appears as though the neurons of Lesuisse that are exposed to B27, pass through stage 3, and are provided at stage 5 . Kaech provides for a protocol for culturing hippocampal neurons, wherein Kaech explicitly shows the neurons developing dendrites in a manner consistent with the transition from the claimed stage 3, to stage 5. See page 2406, “Abstract” section; page 2410, Figure 2; page 2414, 1 st [full] paragraph and Figure 7. Kaech indicates that hippocampal neuron cultures are preferably culturing in either N2 or B27 media supplements. See page 2407, last [full] paragraph; page 2408, Table 1; page 2410, step 22; page 2411, step 30. Based upon both Lesuisse and Kaech, it is clear that B27 media supplement is routinely provided with neuronal cell cultures, and it is further clear that this media supplement allows for neuronal cells to develop from stage 1 to stage 5. Although the prior art does not explicitly provide a method of exposing stage 3 neurons to B27, and ultimately acquire stage 5 neurons, with mature dendrites, it would be clear to the ordinary artisan that cultured neurons must include B27 media supplement, and when cultured immature neurons are exposed to B27, they develop mature dendrites . Since both of the prior art references teach the claimed method, wherein stage 3 neurons develop into stage 5 neurons, with mature dendrites, the references must necessarily anticipate the claimed method. However, since the prior art references do not explicitly start at stage 3 neurons, it could be suggested that the development of neurons from stage 3 to stage 5, with mature dendrites, would be obvious to the ordinary artisan; and if said ordinary artisan wanted to culture stage 3 neurons, in order to develop stage 5 neurons, it would be obvious to supplement their media with B27. With respect to claim 1, both Lesuisse and Kaech teach the claimed method. With respect to claim 2, based upon the images provided, Lesuisse teaches the claimed dendritic spines. Additionally, Kaech teaches stage 5 neurons, which necessarily include the claimed dendritic spines. With respect to claim 3, although the cited prior art does not teach these markers and structures, the references anticipate the method and provide for cells that appear to match the claimed phenotype. As such, these features must have inherently been present. With respect to claim 4, although Lesuisse teaches the marker MAP2, Lesuisse does not describe neuronal stages. See page 9, “Abstract” section. However, the references anticipate the method and provide for cells that appear to match the claimed phenotype. As such, these features must have inherently been present. With respect to claim 7, based upon Lesuisse and Kaech, the claimed cells are described in the prior art . Claim Rejections - 35 USC § 103 07-21-aia AIA Claim s 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Lesuisse, et al ( Journal of neurobiology , 5, 9-23, 2002) Kaech, et al ( Nature Protocols , 1, 2506-2415, 2006) and Bianchi, et al ( Stem Cell Research , 32, 126-134, 2018). See the discussion of Lesuisse and Kaech, above. Both references teach the maturation, and dendrite formation, of native neurons, and do not describe neurons formed from induced pluripotent stem cells (iPSCs) . Bianchi teaches methods of differentiating iPSCs into “functional motor neurons.” See page 126, “Abstract” section. Although Bianchi does not teach neurons with dendrites, it would be reasonable to assume that a “functional motor neuron” possesses structures that would make it “functional,” like dendrites. Bianchi provides for methods of differentiating iPSCs into neural progenitor cells, then neural progenitor cells into mature motor neurons, wherein both differentiation protocols include B27. See page 128, left column, sections 2.2 and 2.3. Based upon the fact that Bianchi shows that the iPSCs can generate functionally and structurally identical neuronal cells, wherein B27 can be included in the differentiation protocol, would suggest that iPSCs can be used as obvious variants of their naturally occurring variants that are directly isolated from brain tissue. The differentiated iPSCs of Bianchi would be obvious to use because they appear identical to cells isolated from brain tissue, and can be considered obvious variants . Conclusion 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Poole (WO 2008/118421A1); Harrill, et al ( In Vitro Cellular Developmental Biology-Animal , 51, 612-629, 2015) . Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM. 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, Melenie Gordon can be reached at 571-272-8037. 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. /DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651 Application/Control Number: 18/332,209 Page 2 Art Unit: 1651 Application/Control Number: 18/332,209 Page 3 Art Unit: 1651 Application/Control Number: 18/332,209 Page 4 Art Unit: 1651 Application/Control Number: 18/332,209 Page 5 Art Unit: 1651 Application/Control Number: 18/332,209 Page 6 Art Unit: 1651 Application/Control Number: 18/332,209 Page 7 Art Unit: 1651 Application/Control Number: 18/332,209 Page 8 Art Unit: 1651 Application/Control Number: 18/332,209 Page 9 Art Unit: 1651 Application/Control Number: 18/332,209 Page 10 Art Unit: 1651 Application/Control Number: 18/332,209 Page 11 Art Unit: 1651