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 .
CONTINUED EXAMINATIONS
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/19/26 has been entered.
DETAILED ACTION
Applicant’s amendment in the reply filed on 3/19/26 is acknowledged, with newly added claims 19-23. Claims 2-16, and 19-23 are pending. Claims 2-16, and 19-23 are examined on the merits.
Any rejection that is not reiterated is hereby withdrawn.
Claim Objections
Claim 9 is objected to because of the following informalities: Claim 9 recites “laminin” twice at lines 3 and 4, which is redundant.
Claim Rejections –35 USC § 112, 2nd
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 2-16, and 19-23 are newly rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
This is a new rejection necessitated by the Applicant’s amendment filed on 3/19/26.
Claim 2 has two “a)”s in the claim.
Claim 6 recites “at least one SHH activator” at line 7, however, there is no “and” or “or” before “at least one SHH activator”, and it is not clear whether those components have to be all present in the neural medium, or only one is sufficient. The claim is construed as “or at least one SHH activator”.
Therefore, the metes and bounds of claims are rendered vague and indefinite. The lack of clarity renders the claims very confusing and ambiguous since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
All other cited claims depend directly or indirectly from rejected claims and are, therefore, also, rejected under U.S.C. 112, second paragraph for the reasons set forth above.
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 2-4, 6-16, 21, and 23 are newly rejected under 35 U.S.C. 102 (a)(1) as being anticipated by ÅAstrand (ÅAstrand, Assembly of FN-silk with laminin-521 to integrate hPSCs into a three-dimensional culture for neural differentiation. Biomaterials science, (2020 May 07) Vol. 8, No. 9, pp. 2514-2525. Electronic Publication Date: 26 Mar 2020).
This is a new rejection necessitated by the Applicant’s amendment filed on 3/19/26.
ÅAstrand teaches three-dimensional (3D) neural tissue cultures recapitulate the basic concepts during development and disease better than what can be obtained using conventional two-dimensional cultures. Here, we use a recombinant spider silk protein functionalized with a cell binding motif from fibronectin (FN-silk) in combination with a human recombinant laminin (thus claims 9 and 21 are met) 521 (LN-521) to create a fully defined stem cell niche in 3D. A novel method to assemble silk blended with LN-521 together with human pluripotent stem cells (hPSC) (thus claim 3 is met) is used to create centimeter-sized foams, which upon cultivation develop into 3D cell constructs supported by a microfibrillar network. After initial cell expansion, neural differentiation was induced to form a homogenous layer of continuous neuroectodermal tissue that allows further differentiation into neuronal subtypes. The silk-supported 3D cell constructs could then be detached from the bottom of the well and cultured as floating entities, where cells appeared in distinctive radial organization resembling early neural tube. This shows that the neural progenitors retain their cellular self-organization ability in the FN-silk/LN-521-supported 3D culture. Calcium imaging demonstrated spontaneous activity, which is important for the formation of neuronal networks. Together, the results show that hPSCs integrated into FN-silk/LN-521 foam develop into neural progenitors and that these stay viable during long-term differentiations. FN-silk/LN-521 also supports morphogenesis mimicking the human brain development and can serve as base for engineering of hPSC-derived neural tissue (see Abstract) (thus claim 16 is met).
ÅAstrand teaches as previously described, pluripotent cells integrated into foams made of FN-silk/LN-521 can be expanded for 3 days (thus claim 2a) and 2b), and claim 7, claim 23 a) and 23b) are met) to gain sufficient density for initiation of neural differentiation (Fig. 2). Neural differentiation was induced with a medium (NIM) including Noggin and SB431542 (thus claim 6 is met). After seven days (thus claims 12 and 13 are met), the colonies of neural progenitors had expanded throughout the foam (Fig. 3B) (page 2518, 2nd column, 2nd paragraph).
ÅAstrand teaches 50 000 hPSCs resuspended in culture medium (typically 10 000–15 000 cells per μl) (thus claim 10 is met) in presence of 10 μg ml−1 Rock inhibitor Y27632 (VWR) were added directly into the foam and distributed by 5 additional strokes with the pipette. The foams were stabilized for 15 min at 37 °C, 5% CO2 in a cell incubator before submerged with 0.7 ml Essential 8™ (ThermoFisher) supplemented with 10 μg ml−1 Y27632 (thus claim 14 is met). Rock inhibitor was omitted in the medium from 16–20 hours after seeding (page 2515, 2nd column, 3rd paragraph) (thus claims 2c, 2d, 11, 23 c) and 23 d) are met).
ÅAstrand teaches immunofluorescence analysis of 3D cultures sectioned 60 (thus at least 40 days, thus claim 15 is met) days after initiation of differentiation revealed multiple regions of SOX2+ cell populations radially organized around the channels and surrounded by layers of cells positive for BIII-TUBULIN (page 2520, 2nd column, 2nd paragraph from the bottom).
ÅAstrand teaches together, this demonstrates the ability of hPSCderived neural progenitors to spontaneously form cerebral structures (thus the claimed cerebral tissue, thus claim 2 is met) with active, signaling progenitors, thereby recapitulating the early neurodevelopment (page 2521, 1st column, 2nd paragraph from the bottom).
ÅAstrand teaches when analyzing the cell proliferation for HS980 and a human
induced pluripotent cell line (hiPS, C5)21 after three days in FN-silk/LN-521 and compared with 2D control (thus claim 8 is met), no difference could be detected (page 2518, 1st column, last paragraph).
Therefore, the reference is deemed to anticipate the instant claim above.
Claim 23 is newly rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Ge et al (CN 105738458 A).
This is a new rejection necessitated by the Applicant’s amendment filed on 3/19/26.
Ge et al teach measuring retinal nerve cell (thus neural tissue composition, thus claim 23 is met) potential involves (a) using three-dimensional human induced pluripotent stem cell (iPSc) (thus 23a is met) derived digested retinal nerve fiber layer as single cells, taking single cells as seed cells, coating seed cells after resuspending in differentiation inducing medium with matrigel (thus a 3D cell culture substrate, thus 23c is met, thus an in vitro method of producing a three dimensional neural tissue, thus suspension and resuspended, thus claim 23 b) is met) polylactic acid-glycolic acid polymer to obtain retinal nerve cell, where the differentiation inducing medium (thus 23 d is met) comprises neurotrophic factor, and (b) recording ion channel currents in whole-cell recording mode, and detecting retinal nerve cell potential, and retinal nerve cell basic functions (see Abstract).
Therefore, the reference is deemed to anticipate the instant claim above.
Claim Rejections –35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 2-4, 6-16, 19, 21, and 23 are newly rejected under 35 U.S.C. 103(a) as being unpatentable over ÅAstranas applied to claims 2-4, 6-16, 21, and 23 above.
This is a new rejection necessitated by the Applicant’s amendment filed on 3/19/26.
The teachings of ÅAstranare set forth above and applied as before.
The teachings of ÅAstran do not specifically teach the claimed confluence in claim 19.
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 vary amount of confluence according to cell concentration and incubation time. Determining an appropriate confluence percentage is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
From the teachings of the references, it is apparent that one of the ordinary skills in the art would have had a reasonable expectation of success in producing the claimed invention.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Applicant’s arguments have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of ÅAstranare. In addition, claim 23 does not recite anything about cerebral tissue, thus the argument is not applicable to claim 23.
Conclusion
No claim is allowed (claims 5, 20, and 22 are free of art).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIUWEN MI whose telephone number is (571)272-5984. The examiner can normally be reached on Monday-Friday 8:30 am to 5:00 pm.
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/Qiuwen Mi/
Primary Examiner, Art Unit 1655
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