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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 20, 2025 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed June 20, 2025 is acknowledged. Claims 1-8, 11-16, 20-21 are canceled. Claims 9-10, 17-19 are amended. Claims 9-10 and 17-19 are pending in this application. Claim 10 is withdrawn without traverse (filed 10/11/2022) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was without traverse in the reply filed on October 11, 2022.
4. Claims 9 and 17-19 are under examination in this office action.
5. Applicant’s arguments filed on June 20, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
6. The rejection of claims 11 and 20-21 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is moot because the claims are canceled.
.
Claim Rejections/Objections Maintained
In view of the amendment filed on June 20, 2025, the following rejections are maintained.
Claim Objections
7. Claim 10 is objected to because of the following informalities: the status of the claim 10 is incorrect because the claim is withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Claim Rejections - 35 USC § 112
8. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 9 and 17-19 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The rejection is maintained for the reasons made of record and the reasons set forth below.
Claims 9 and 17-19 as amended encompasses a genus of a population of purified human retinal progenitor cells differentiated from human epithelial cells, wherein the human retinal progenitor cells express one or more VSX2, VAX2 and SIX6, and comprises a genus of nucleotide sequences encoding a genus of a reporter gene operably linked to a genus of nucleotide sequences encoding human PAX6D, wherein retinal lineage genes upregulated by PAX6D include one or more of fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1.
The specification fails to provide sufficient species for the broad genus of purified human retinal progenitor cells expressing one or more VSX2, VAX2 and SIX6 and comprising the broad genus of nucleotide sequences encoding a genus of a reporter gene operably linked to a genus of nucleotide sequences encoding human PAX6D, wherein retinal lineage genes upregulated by PAX6D including one or more of fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1.
Response to Arguments
On p. 4 of the response, Applicant argues that the rejection has been overcome in view of amendment to the claims.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of the claimed genus of human retinal progenitor cells expressing one or more VSX2, VAX2 and SIX6 and comprising a nucleotide sequence encoding a reporter gene operably linked to a nucleotide sequences encoding human PAX6D and wherein retinal lineage genes including one or more of fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1 are upregulated by PAX6D because:
i. There is no well-established structural and functional relationship or correlation between the claimed human retinal progenitor cells recited in claim 9, and the human retinal progenitor cells expressing VSX2, VAX2 and SIX and differentiated from neuroepithelial cells that are differentiated from PAX6-KO/PAX6D-TetON-H9 hESC cells induced with DOX (i.e. hESC cells with a PAX6 KO background and with a PAX6D-TetOn plasmid induced by DOX), and wherein retinal lineage genes including fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1 are upregulated by PAX6D as shown on p. 24-27 of the instant specification.
ii. The specification only describes human retinal progenitor cells (hRPCs) expressing VSX2, VAX2 and SIX and comprising a plasmid of PAX6D-TetON, and wherein the hRPCs are differentiated from human neuroepithelial cells that contain no PAX6 gene (PAX6-KO) and comprise the plasmid of PAX6D-TetON and induced with DOX, and wherein retinal lineage genes including fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1 are upregulated by DOX-induced expression of PAX6D.
The human neuroepithelial cells shown in Examples contain no endogenous PAX6 gene and comprise a DOX-inducible plasmid of PAX6D-TetON, and are differentiated from H9 hESC cells that are with a PAX6-KO background and contain a PAX6D-TetOn plasmid inducible by DOX.
Neither the specification nor the prior art teaches that human neuroepithelial cells comprising an endogenous wild type PAX6 gene (which will express all four PAX6 isoforms PAX6A-D) will have the same expression profiles as the human neuroepithelial cells with NO endogenous PAX6 gene and comprising a plasmid of PAX6D-TetON and induced with DOX.
iii. Based on Applicant’s own admission, the protein expression profiles of neuroepithelial cells from wild type are very different from those of neuroepithelial cells with PAX6 KO and PAX6D KO (see para. [0084]; [0090]-[0092]).
Based on Applicant’s own admission, “All the PAX6D coding sequences (CDS) are shared by PAX6A and PAX6B…….PAX6 isoform transcription is controlled by separate promoters and PAX6D has an additional exon (exon alpha) in its 5’-UTR…” (see p. 22, [00088], lines 3-9 of the instant specification) and “….. Pax6APD (or PAX6D in human) shares all the coding sequences with other isoforms…..” (p. 38, paragraph [000104], lines 11-22 of the instant specification).
The claimed human retinal progenitor cells differentiated from human neuroepithelial cells comprising an endogenous wild type PAX6 gene will express all four PAX6 isoforms PAX6A-D. Based on Applicant’s own, PAX6A does not restore the PAX6 function in retinal specification (see [00095 of the specification).
Neither the specification nor the prior art teaches whether human retinal progenitor cells differentiated from human neuroepithelial cells comprising an endogenous wild type PAX6 gene and comprise a nucleotide sequence encoding a reporter gene operably linked to a nucleotide sequence encoding human PAX6D will express one or more of VSX2, VAX2 and SIX6 and upregulate one or more retinal lineage genes including fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1 genes and repress one or more of mytl1, wnt8b and dcx genes.
The specification also fails to teach what specific nucleic sequences can encode a reporter gene operably linked to a nucleic sequence encoding human PAX6D in human retinal progenitor cells but not other PAX6 isoforms in human neuroepithelial cells comprising a wild type PAX6 gene; and simultaneously upregulate one or more of fgf5, foxp2, tenm3, yy1, dmbx1 and mbnl1 by the encoded human PAX6D, and expression of VSX2, VAX2 and/or SIX6 in the human retinal progenitor cells.
Since the common characteristics/features of the claimed genus of human retinal progenitor cells comprising the claimed genus of nucleic sequence are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of human retinal progenitor cells comprising the claimed genus of nucleic sequence.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Therefore, the claimed human retinal progenitor cells expressing VSX2, VAX2 and/or SIX6 and comprising a nucleotide sequence encoding a reporter gene operably linked to a nucleotide sequence encoding human PAX6D have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 9 and 17-19 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is maintained.
Conclusion
9. NO CLAIM IS ALLOWED.
10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mellough et al. (Stem cells, 2012; 30:673-686) teaches differentiation of hESCs and hiPSCs into retinal lineages (see abstract).
Park et al. (Stem cell & Dev., 2018; 27: 367-377. DOI:10.1089/scd.2017.0283) teaches PAX6 alternative splicing isoforms and their role in corneal development (see p. 367, abstract).
Zhang et al. (Cell Stem Cell, 2010; 7:90-100. DOI 10.1016/j.stem.2010.04.017) teaches differentiation of hESCs into neuroectoderm by overexpression of Pax6a or Pax6b but not Pax6∆PD (see abstract).
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
February 20, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675