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
To expedite the compact prosecution, the Examiner is pursuing the amended claims dated 30 July 2025, in which applicant; amended claims 1, 11, 16, 19, 29, 33, 38, 42, 51, 54, 55, 62, 67, 69, 70; canceled claims 3-8, 10, 12-15, 17-18, 20-28, 31-32, 35-37, 39-41, 43-50, 52-53, 56-61, 63-66, 68, 71-72, 74-77. Therefore, claims 1-2, 9, 11, 16, 19, 29-30, 33-34, 38, 42, 51, 54-55, 62, 67, 69-70 and 73 are pending in the application.
Accordingly, claims 1-2, 9, 11, 16, 19, 29-30, 33-34, 38, 42, 51, 54-55, 62, 67, 69-70 and 73 are under current examination.
Priority
This application was filed 10/10/2024 and is a 371 application of PCT/US2023/065631 filed on 04/11/2023, which claims benefit to the Priority from Provisional Application 63329713 filed on 04/11/2022. Thus, the earliest possible priority for the instant application is 04/11/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/30/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, and the signed and initial PTO Forms 1449 are mailed with this action.
Claim Objections
Claim 1 is objected to because of the following informalities: abbreviations such as “AKL” should be spelled out in full 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.
Claim 2 and 11 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cosset et al., (JoVE (Journal of Visualized Experiments), (148), p.e59682; 2019; cited in IDS filed 09/10/2025; hereinafter “Cosset”).
Regarding claims 2 and 11, Cosset discloses the generation of dopaminergic organoids from hESCs in a microwell culture plate. The method a Rock inhibitor, dual SMAD inhibition and SHH in microwells to differentiate the hsECs, wherein culturing the cells in microwells to form spheroids (see 2 “hESC-derived neural organoids for GBM studies” ¶).
Accordingly, Cosset anticipates the instant claims 2 and 11.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-2, 11, 16, 19, 29-30, 33-34, 38, 42, 51, 69, 70, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Bratt-Leal et al., (WO2021146349A1, Publication Date: 22 July 2021; cited in IDS filed 09/10/2025; hereinafter “Bratt-Leal”), in view of Neely et al., (ACS chemical neuroscience, 3(6), p.482, 2012; cited in PTO892; hereinafter “Neely”).
With respect to claims 1-2, 11, 38, 69, 70, and 73, Bratt-Leal describes the generation of neural spheroids in microwells from ESCs and iPSCs. The cells are exposed to (i) an inhibitor of TGF-[Symbol font/0x62]/activing-Nodal signaling (SB431542); (ii) at least one activator of SHH signaling (SHH or purmorphamine [0185]); (iii) an inhibitor of BMP signaling (LDN193189); and (iv) an inhibitor of GSK313 signaling (CHIR99021 ); and (b) performing a second incubation including culturing cells of the spheroid in a substrate-coated culture vessel under conditions to neurally differentiate the cells ([0152], [0143] of Bratt-Leal). Further, the population of spheroids comprises administering to the subject a therapeutically effective amount of the population of neural cells treating mammalian subject (e.g., a human) for neurodegenerative diseases ([0122] of Bratt-Leal).
Still, regarding claim 1, Bratt-Leal contacting the stem cells with a differentiation composition is ALK inhibitors (e.g., DMH1). However, such was known in the prior art.
Neely demonstrates that ALK inhibitors DMH1 induces neural progenitors that can subsequently differentiated into β3-tubulin expressing neurons, a subset of which also express tyrosine hydroxylase. Neely further demonstrates that DMH1 in combination with small molecule modulation of TGF-β signaling pathways, provides efficient conversion of hES and hiPSCs into neural precursor cells. Accordingly, Neely teaches the use of DMH1 as an ALK inhibitor in the differentiation composition for promoting neural differentiation of PSCs (abstract, p. 484 last ¶ and Fig. 3 of Neely).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to POSITA at the time of filling to modify the method of Bratt-Leal by contacting the ALK inhibitor DMH1, as taught by Neely, because Neely demonstrates that DMH1 mediated ALK inhibitor signaling promoted efficient conversion of hiPSCs into neural progenitor cells capable of further differentiation into β3-tubulin expressing neuron (abstract, p. 484 last ¶ and Fig. 3 of Neely). POSITA would have been motivated to incorporate DMH1 into the differentiation methos of Bratt-Leal to promote and/or enhance neural differentiation of PSCs with a reasonable expectation of successfully obtaining neural progenitor cells and differentiated neuronal cells.
Regarding claim 16, Bratt-Leal teaches that the contacting the cells comprises contacting the cells for a time period of about 1-7 days of substantially continuous contact ([0184] of Bratt-Leal).
Regarding claim 19, Bratt-Leal teaches that the contacting the stem or progenitor cells with a Rho Kinase (ROCK) inhibitor and wherein the ROCK inhibitor comprises Y27632 (0221]-[0224] of Bratt-Leal).
Regarding claims 29-30, Bratt-Leal teaches that the neural cells are further defined as dopaminergic neurons ([0394], [0396] of Bratt-Leal).
Regarding claims 33-34, Bratt-Leal teaches that the cells are further contacted with a GSK3 (glycogen synthase kinase 3) inhibitor (i.e., CHIR99021) for a period of time ([0152], claim 58 of Bratt-Leal).
Regarding claim 42, Bratt-Leal teaches that the contacting the cells with one or more of cAMP, GDNF, BDNF, TGFβ3 (claim 14 of Bratt-Leal).
Regarding claim 51, Bratt-Leal teaches that the on day 7, performing a second incubation to neurally differentiate cells of the spheroid, comprising culturing the cells in a culture vessel coated with a substrate selected from among: laminin, collagen (claim 14 of Bratt-Leal).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Subject Matter Free of Art.
According to IFW-Search Notes, and PE2E search report, the examiner has been unable to discover any art that disclose the claim limitation of claims 9, 54-55, 62, 67 where method for differentiating stem or progenitor cells into neural cells, the method comprising ALK inhibitors exclude LDN193189 and/or SB431542. Therefore, claims 9, 54-55, 62, 67 are objected because art does not teach or reasonably suggest the claims limitation. Since claims 9, 54-55, 62, 67 depend on rejected base independent claim 1. Claims 9, 54-55, 62, 67 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
