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. Claim Status Claims 1-2, 6, 10-19, 24 and 28 are pending. Claims 12-19 and 24 are withdrawn. Claims 1-2, 6, 10-11 and 28 are under examination. Election/Restrictions Applicant’s election without traverse of the following invention Inv ention Group I, claims 1-2, 6, 10 -11 and 28, drawn to a composition, which comprises a SMAD signaling pathway inhibitor, a SHH signaling pathway agonist, a Wnt signaling pathway agonist and a Myosin II ATPase inhibitor, a cell culture medium comprising the composition, and a kit comprising the composition in the reply filed on 23 rd , December, 2025 is acknowledged. Claims 12-19 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Applicant’s election of the following species Species the culture medium comprises the composition of claim 1 and a basal culture medium, the basal culture medium being selected from the group consisting of DMEM/F 1 2, Neurobasal, Neural Induction Media or X-VIVO, and supplemented with a N2 supplement and a stabilized di peptide of L-alanyl-L-glutamine ( claim 10 ) , in the reply filed on 23 rd , December, 2025 is acknowledged. Claims 1-2, 6, 10 -11 and 28 encompass the elected species. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as a species election without traverse (MPEP § 818.01(a)). Claim Objections Claim s 2 and 10 are objected to because of the following informalities: Claim 2 includes periods before the end of the claim (e.g. “a.” in claim 2 ). Periods are only allowed at the end of a claim. Applicant is directed to MPEP 608.01(m) which states “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck , 36 USPQ2d 1211 (D.D.C. 1995). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75( i ) . ” To overcome this objection to claim 2, it is reco mmended that Applicant amend all instances of periods before the end of the claim to parentheses (for example, “ a .” in claim 2 would be amended to “a)” or “(a)”). Claim 10 recites its subparts with numbers rather than letters. To improve the clarity, it is recommended to label the subparts of claim 10 with letters. Appropriate correction is required. 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 appl icant regards as his invention. Clai ms 1-2, 6, 10-11 and 28 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. Claims 1-2 are vague and indefinite in the use of parenthesis, since it is unclear whether the parenthetical material is or is not intended to be part of the claim. By nature of their ultimate dependency on claim 1, claims 2, 6, 10-11 and 28 are also rejected. Claim s 1-2 recite exemplary language (“e.g.”). Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim (see MPEP 2173.05(d)). By nature of their ultimate dependency on claim 1, claims 2, 6, 10-11 and 28 are also rejected. Claims 2, 6 and 10 recite “preferably . ” If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim (see MPEP 2173.05(d). Therefore, it is unclear which aspect(s) of the claim is/are intended to be within the scope(s) of the claim(s) (see also MPEP 2173.05(b)). By nature of its dependency on claim 10, claim 28 is also rejected. Claim 6 recites “the composition according to claim 1, which comprises a BMP inhibitor, a TGF β /Activin-Nodal inhibitor, a SHH protein, a Smoothened agonist, a GSK3 β inhibitor, a Myosin II ATPase inhibitor, and optionally a ROCK inhibitor; preferably, it comprises LDN193189, SB431542, a recombinant SHH, SAG, CHIR99021, Blebbistatin , and optionally Y- 27632; alternatively, the composition consists of a BMP inhibitor, a TGF β /Activin-Nodal inhibitor, a SHH protein, a Smoothened agonist, a GSK3 β inhibitor, a Myosin II ATPase inhibitor, and optionally a ROCK inhibitor; preferably, the composition consists of LDN193189, SB43 1 542, a recombinant SHH, SAG, CHIR99021, Blebbistatin and optionally Y-27632.” As discussed above, this claim is indefinite due to the preferential language of “preferably.” Claim 6 is also indefinite for additional issues. Specifically, the claim recites specific components which overlap with those recite in claim 1 , upon which is depends. However, claim 6 does not refer back to those components, so it is unclear whether the components recited in claim 6 are encompassed by the broader recitations in claim 1 , or whether they are additional components in the composition. These are discussed specifically below. Claim 6 recites “ a BMP inhibitor ” and a “ TGF β /Activin-Nodal inhibitor ” as well as “ LDN193189 ” and “ SB431542 ” which are each SMAD inhibitors. For each of these embodiments, i t is un clear whether one of both of t hese are the SMAD inhibitor recite d in claim 1 , upon which claim 6 depends, or whether they are additional components in the composition. Claim 6 recites “ a SHH protein ” and “ a Smoothened agonist ” as well as “ a recombinant SHH ” and “SAG” which are each “ a SHH signaling pathway agonist .” It is unclear whether one of both of these are the SHH signaling pathway agonist recited in claim 1 , upon which claim 6 depends, or whether they are additional components in the composition. Claim 6 recites “ GSK3 β Inhibitor ” or “ CHIR99021 ” which are Wnt signaling pathway agonist s. Because claim 6 does not refer back to the Wnt signaling pathway agonist of claim 1, it is unclear whether each of these are the Wnt signaling pathway agonist recited in claim 1 , upon which claim 6 depends, or whether they are additional components in the composition. Claim 6 recites “ a Myosin II ATPase inhibitor ” or “ Blebbistatin ” which are Myosin II ATPase inhibitor s. Because claim 6 does not refer back to the Myosin II ATPase inhibitor of claim 1, it is unclear whether each of these are the Myosin II ATPase inhibitor recited in claim 1 , upon which claim 6 depends, or whether they are additional components in the composition. Claim 6 recites “ Y-27632 ” which is a ROCK inhibitor Because claim 6 does not refer back to the ROCK inhibitor of claim 1, it is unclear whether the recited Y-27632 is the ROCK inhibitor recited in claim 1 , upon which claim 6 depends, or whether it is an additional component in the composition. Claim 10 c ontains the trademark/trade name s DMEM, Neurobasal, X-VIVO, CTS TM , KnockOut TM , GlutaMax TM and B27. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe cell culture media components and, accordingly, the identification/description is indefinite. Because th e reagent s was developed by the manufacturer at the time of the applicant’s invention under the trade nam es and as a result are proprietary, which means what constitutes as DMEM, Neurobasal, X-VIVO, CTS TM , KnockOut TM , GlutaMax TM or B27 can change, and these changes do not need to be disclosed by these companies to the public. Accordingly, the identification of the trade name is indefinite and the applicant is advised to employ a sequence, the SeqID , IUPAC name and/or CAS number for this agent. By nature of its dependency on cla i m 10, claim 28 is also rejected. Claim Interpretation Due to the 112b issues identified above, for the sake of compact prosecution, the claims identified with 112 issues above are being examined against the prior art and double-patenting as follows: Preferential limitations are interpreted as optional. F or the sake of compact prosecution, for the purpose of applying past art, consideration is being given to the trademarks recited in the claims. However, as stated above, trademarks/trade names and are not allowed in claims . 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. Claim s 1-2 and 10 -11 and 28 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by McMahon et al. ( US - 2018/0051248 - A 1; henceforth McMahon) . Regarding claim 1 , McMahon discloses a composition which comprises SMAD signaling pathway inhibitor (Dorsomorphin) , a SHH signaling pathway agonist (C25II SHH or Purmorphamine ), a Wnt signaling pathway agonist (CHIR 99021) and a Myosin II ATPase inhibitor ( Blebbistatin ) (D5 Aggregate Formation Medium; Table 2 pg. 16). Regarding claim 2 , further to the discussion of claim 1 above, as stated above (see claim 1 rejection above) McMahon discloses the composition comprises: the Myosin II ATPase inhibitor is Blebbistatin ; the SMAD signaling pathway inhibitor is Dorsomorphin which is a BMP inhibitor; the SHH signaling pathway agonist is a terminal modified SHH protein ( C25II SHH ) a Smoothend agonist which is Purmorphamine , ( Purmorphamine ) and a combination thereof ( C25II SHH or Purmorphamine ) ; the Wnt signaling pathway agonist is C HIR99021 which is a GSK3β inhibitor. Regarding claim 2 , it is noted that the transitional phrase “characterized by” is interpreted to be synonymous with comprising (“ The transitional term "comprising", which is synonymous with "including," "containing," or " characterized by ," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. MPEP 2111.03). Regarding claim 10 , further to the discussion of claim 1 above, McMahon discloses the composition compris ing the composition of claim 1 and a basal culture medium, the basal culture medium being DMEM/F12 ( D5 Aggregate Formation Medium; Table 2 pg. 16) . Regarding claim 10 , it is noted that the basal culture medium supplements are currently claimed as preferential limitations which are interpreted as optional limitations (see claim interpretation above). Applicant is directed to MPEP 2111.04 which states that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.” Therefore, in the instant case, because the basal culture medium supplements are optional, the requirements of claim 10 are met by McMahon. Regarding claims 11 and 28 , further to the discussion of claims 1 or 10 above, respectively, as stated above (see claims 1 and 10 rejection above), McMahon discloses the required claim components for the composition ( claim 1 ), and the cell culture media ( claim 10 ). Regarding the preamble of “a kit” of claims 11 and 28 , the preamble merely states the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and therefore the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02 ) See also Rowe v. Dror , 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation") . In the instant case, as set forth above, McMahon discloses all the structural requirements of claims 11 and 28 and therefore the composition disclosed by McMahon is capable of meeting the intended use of “a kit” and meets instant claim limitations. Accordingly, McMahon anticipates instant claims. 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 . Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable McMahon et al. (US-2018/0051248-A1; henceforth McMahon) . The teachings of McMahon above are hereby incorporated in their entirety. Regarding claim 6 , further to the discussion of claim 6 above, as stated above, McMahon discloses the composition comprises: the Myosin II ATPase inhibitor is Blebbistatin ; the SMAD signaling pathway inhibitor is Dorsomorphin which is a BMP inhibitor; the SHH signaling pathway agonist is a terminal modified SHH protein ( C25II SHH ) a Smoothend agonist which is Purmorphamine , ( Purmorphamine ) and a combination thereof ( C25II SHH or Purmorphamine ) ; the Wnt signaling pathway agonist is C HIR99021 which is a GSK3β inhibitor. Regarding claim 6 , while McMahon teaches including a single SMAD signaling pathway inhibitor of Dorsomorphin which is a BMP inhibitor in the composition (D5 Aggregate Formation Medium; Table 2 pg. 16) , McMahon teaches TGF β /Activin-Nodal inhibitor s as SMAD inhibitors (para. [0005, 0007, 0051, 0053, 0055, 0082, 0084-0088, 0090]) , and McMahon teaches TGFβ/Activin-Nodal inhibitors ( transforming growth factor (TGF) antagonists; para. [0089]) may be included in the differentiation medium, McMahon is silent to a specific embodiment comprising a BMP inhibitor, a TGFβ/Activin-Nodal inhibitor, a SHH protein, a Smoothened agonist, a GSK3β inhibitor and a Myosin II ATPase inhibitor. Nevertheless, regarding claim 6 , Applicant is directed to which MPEP 2144.06 indicates that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven , 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, regarding claim 6 , in the instant case, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the composition of McMahon, which includes a SMAD inhibitor and combine the TGFβ/Activin-Nodal inhibitor of McMahon , which is also a SMAD inhibitor, in order to form a third composition to be used for the very same purpose . Regarding the reasonable expectation of success, McMahon evidences preparation of compositions that include SMAD inhibitors ( (D5 Aggregate Formation Medium; Table 2 pg. 16) . Hence, the claimed invention as a whole was prima facie obvious. Claims 11 and 28 is rejected under 35 U.S.C. 103 as being unpatentable McMahon et al. (US-2018/0051248-A1; henceforth McMahon) in view of Ahern (The Scientist Magazine, 1995 Archive accessed at https://www.the-scientist.com/technology/biochemical-reagents-kits-offer-scientists-good-return-on-investment-58425 ). The teachings of McMahon above are hereby incorporated in their entirety. Regarding claims 11 and 28 , further to the discussion of claims 1 or 10 above, respectively, McMahon does not teach a kit comprising the compositions. Nevertheless, regarding claims 11 and 28 , Ahern teaches preparing Kits to allow the product to be readily used in research by other scientists to accelerate the research process and allow them to spend more time on their primary research focus, rather than preparing reagents (pg. 3-5). Therefore, regarding claims 11 and 28 , it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the compositions disclosed by McMahon, and make them into a kit as suggested by Ahern to obtain the predictable result of a kit will cell culture components with a reasonable expectation of success. One of ordinary skill would have been motivated to do so as taught by Ahern because making the compositions into a kit would allow the product to be readily used in research by other scientists to accelerate the research process and allow them to spend more time on their primary research focus, rather than preparing reagents, as taught by Ahern (pg. 3-5). Regarding the reasonable expectation of success, Ahern evidences Kits (pg. 3-4). Hence, the claimed invention as a whole was prima facie obvious. Pertinent Art The prior art of George et al. ( US - 2015/0265652 - A 1; see IDS filed 3 rd , December, 2024; henceforth “George”), made of record but not relied upon, is considered pertinent to Applicant’s disclosure. George discloses a composition, which comprises: a SMAD signaling pathway inhibitor (a BMP inhibitor of LDN-193189 and TGFβ-signaling inhibitor of SB431542 ) a SHH signaling pathway agonist ( 2 μM purmorphamine and 100 ng/mL Shh C25II ) and a Wnt signaling pathway agonist ( CHIR 99021 ; para. [0165]). George does not teach a single specific composition that also includes a Myosin II ATPase inhibitor . Conclusion No claim is allowable. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT BRIANA N EBBINGHAUS whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-4548 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9:30 AM to 5:30 PM ET . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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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. /BRIANA N EBBINGHAUS/ Examiner, Art Unit 1632 /PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632