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 .
Applicant's amendments to the claims and arguments filed on 09-02-2025 have been received and entered. Claims 1, 3, 10, 16 have been amended. Claims 2 has been canceled. Claims 1, 3-18 are pending.
Election/Restrictions
Applicant’s election of Group I (Claims 1-9 and 16), species FOXG1 as the retinal cell marker species, and species a) the second cells form at least one lens, at least one cornea, or combinations thereof (from claim 5) in the reply filed on 18-12-2023 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 6-8, 10-15, 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 18-12-2023.
Claims 1, 3, 4 (species FOXG1 as the retinal cell marker species), 5 (species: the second cells form at least one lens, at least one cornea, or combinations thereof), 9 and 16 are under consideration.
Priority
It is noted that there is no claim in this application for priority either from foreign application or US provisional application. Thus, the effective filing date for this application is the filing date on 01/06/2022.
Withdrawn - Claim Rejections - 35 USC § 101
Claims 1, 3, 4, 5, 9, 16 were rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. In view of Applicants' amendment of base claim 1, introducing the limitation “wherein the 3D brain organoid is devoid of vasculature” and Applicants' arguments, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot.
Withdrawn - Claim Rejections - 35 USC § 112
Claim 16 was 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. In view of Applicants' amendment of claim 16 deleting the term “preferably”, the previous rejection of the claim is hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot.
Maintained in modified form- Claim Rejections - 35 USC § 102 - necessitated by amendments
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.
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, 3-5, 9 and 16 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Lako et al (Pub. No.: US 2017/0218335 A1, Pub. Date: Aug. 3, 2017) as evidenced by Valiente-Soriano et al(Scientific Reports | (2020) 10:7273 | doi: 10.1038/s41598-020-64131-z).
Claim interpretation:
The specification of the claimed invention teaches that the first cells may comprise a structure that represents an optic vesicle. The first cells may comprise retinal pigment epithelium (RPE) cells, photoreceptor cells, amacrine cells, bipolar cells, horizontal cells, ganglion cells, Muller cells or combinations thereof ([00177], page 42). Thus, the above cells are interpreted as the first cells.
The specification of the claimed invention teaches that the second cells may form at least one lens, at least one cornea, or combinations thereof ([00179], page 43). Thus, lens and corneal cells are interpreted as second cells.
Regarding to claim 1, Lako et al provides a method of producing a synthetic retina, comprising: i) providing a three-dimensional stem cell culture throughout the differentiation time course, ii) differentiating the three-dimensional stem cell culture for a first time period in a first neural cell culture medium (Abstract). Lako et al teach 3D differentiation culture and development of the optic cup with hESC/hiPSC: polarized neuroepithelium occurred bilaterally, reminiscent of the early optic vesicles (FIG. 8E), or akin to the optic diverticula of the ventral forebrain prior to the closure of the neural tube (FIG. 8F) ([0156], page 11, right column). The inventors have now surprisingly identified that the addition of a single factor, insulin-like growth factor 1 (IGF-1), to hESC/hiPSC cultures for the entire period of differentiation can orchestrate the generation of ocular-like structures containing various elements of the developing eye including retinal pigmented epithelium (RPE), neural retina, primitive lens and cornea ([0086], page 6).
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Also, Lako et al teach murine ESC derived optic cups undergo differentiation to give rise to a fully laminated neural retina containing all the main retinal cell types including the light sensitive photoreceptors, following the normal sequence of retinal development (FIG. 10) ([0005], page 1).
Regarding to claim 1, the claimed: “wherein the 3D brain organoid is devoid of vasculature” Lako et al are silent about any step of generating vasculature or description of any vasculature. Furthermore, Lako et al teach 3D differentiation culture (In-vitro differentiation culture) and development of the optic cup with hESC/hiPSC: polarized neuroepithelium occurred bilaterally, reminiscent of the early optic vesicles (FIG. 8E) ([0156], page 11, right column, also see Figure 8). Given that there’s no apparent evidence that Lako et al performed the step to generate vasculature (via in-vitro differentiation of hiPSC) that is precluded by the language of claim 1, it is reasonable conclude that Lako et al anticipates the claimed: “wherein the 3D brain organoid is devoid of vasculature”.
Regarding to claim 1, the claimed: “the first cells comprise a layer of retinal pigment epithelium (RPE) cells having a honeycomb shape” Lako et al teach the generation of ocular-like structures containing various elements of the developing eye including retinal pigmented epithelium (RPE), neural retina, primitive lens and cornea ([0086], page 6). Thus, Lako et al teach generation of retinal pigmented epithelium (RPE) cells which inherently have a honeycomb shape as evidenced by Valiente-Soriano et al who teach the classical honeycomb pattern of hexagonal RPE cells densely packed along the entire retina (Page 14, 6th para.). Furthermore, Lako et al teach the generation of RPE cells from induced pluripotent
stem cell to form a synthetic retina which is identical to the claimed invention. Thus, it is expected that the RPE cells of Lako et al are morphologically identical to the claimed invention.
Regarding to claim 3, Lako et al teach the retinal tissue comprises one or more, preferably at least two, of the following cell types: bipolar cells, amacrine cells, ganglion cells and retinal pigmented epithelium (RPE) cells ([0023], page 2).
Regarding to claim 4, Lako et al teach that emergence of the early synthetic retina is characterized by phase bright neuroepithelium (expressing RaX/Pax6), and the outer wall of the cup gives rise to retinal pigmented epithelium, characterized by its dark pigmentation and expression of RPE65 ([0126], page 8). Also, examples of retinal cells arising from hiPSC cultures on day 60 of differentiation which were expressing the photoreceptor marker Crx ([0075], page 5, right column, and also see Fig. 8 (G-L)).
Regarding to claim 5, Lako et al report that insulin-like growth factor 1 (IGF-1) can orchestrate the formation of ocular-like structures containing retinal pigmented epithelium, neural retina, primitive lens and cornea from hESC/hiPSC in vitro ([0153], page 10).
Regarding to claim 9, Lako et al teach FIG. 7 shows IGF-1 treatment facilitates the emergence of ocular accessory structures alongside retinal tissues with markers stained for lens (CRYAA, CRYAB, Y-crystallin, AQPO, BFSP1) ([0074], page 5).
Regarding to claim 16, Lako et al provided the aforementioned synthetic retina or pharmaceutical composition for use in the treatment of retinal disease or ocular injury ([0051], Page 3).
Thus, claims 1, 3-5, 9 and 16 are anticipated by Lako et al.
Response to Arguments
Applicant's arguments filed 09-02-2025 have been fully considered but they are not persuasive.
Applicants argue that the RPE cells of embodiments of the synthetic retina of Lako are shown in Figures 3D, 3E, Figure 6H, and Figure 14 (indicated by arrow in panel c) (reproduced below). However, none of these figures from Lako show a layer of RPE cells where the RPE cells have a honeycomb shape. Instead, the RPE cells of Lako are not spatially regulated and appear to be abnormal and randomly distributed throughout the synthetic retina (Remarks, page 9-11).
Response to Arguments:
Lako et al provide evidence for fully differentiated retina and RPE: “ formation of optic cup which is able to differentiate into a fully stratified neural retina and RPE” ([0077], page 5), and FIG. 14 shows examples of differentiating EBs into clear RPE patches (blue arrow, panel c) at day 33 of differentiation ([0081], page 5). Lako et al stated that “the retinal tissue observed is advantageously organized with a laminar pattern reminiscent of the developing human retina” ([0086], page 6); Thus, RPE cells of Lako et al are normally differentiated and similar to RPE of developing human retina. As per MPEP 2112 (II): inherent feature need not be recognized at the relevant time. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)
There is no teaching/description of Lako et al to say RPE abnormal or different from normal RPE cells from human retina. The fact that Lako et al teach EBs differentiated into clear RPE patches at day 33 in FIG. 14 ([0081], page 5) and “the retinal tissue observed is advantageously organized with a laminar pattern reminiscent of the developing human retina” ([0086], page 6) provide evidences for normal differentiation processes and RPE should have classical honeycomb shape as evidenced by Valiente-Soriano et al who teach the classical honeycomb pattern of hexagonal RPE cells densely packed along the entire retina (Page 14, 6th para.).
As per MPEP 716.01(c) (II) arguments by applicant cannot take the place of evidence: Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
Furthermore, as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, there is no evidence that RPE cells having a honeycomb shape provides unexpected/superior results over prior art.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632