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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 7, 2025 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed April 7, 2025 is acknowledged. Claims 1, 3, 12-17, 19, 24, 39, 41, 49, 52, 64, 68 and 71 are canceled. Claims 2, 4-6, 11, 18, 20, 22, 25-26, 69-70 and 72 are amended. Claims 75-77 are newly added. Claims 2, 4-11, 18, 20-23, 25-38, 40, 42-48, 50-51, 53-63, 65-67, 69-70, 72-74 and newly added claims 75-77 are pending in this application. Claims 22-23, 26-38, 40, 42-48, 50-51, 53-63, 65-67 and 74 are withdrawn without traverse (filed 07/22/2022) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable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 made without traverse in the reply filed on July 22, 2022.
4. Claims 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 are under examination with respect to BMP4 in this office action.
5. Applicant’s arguments filed on April 7, 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Claim Rejections/Objections Withdrawn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 1 and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot because the claims are canceled.
The rejection of claims 1 and 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 moot because the claims are canceled.
The rejection of claims 1-2, 4-11, 18-21, 25, 69-70 and 72-73 under 35 U.S.C. 103 as obvious over Nakano et al. (US10501724) in view of Kuwahara et al. (Nat. Commun. 2014; 6:6286. DOI:10.1038/ncomms7286), Hasegawa (Development, 2016; 143:3895-3906, as in IDS) and Kruczek (Ph.D. Thesis, 2016, Division of Bioscience, Department of Cell and Developmental Biology, University College London) is withdrawn in response to Applicant’s amendment to the claims, cancelation of claims 1 and 19 and Applicant’s arguments on p.17-18 of the response.
The rejection of claims 1-2, 4-11, 18-21, 25, 69-70 and 72-73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-22 of US Patent No. 11371016, claims 23-47 of US Patent No. 11214772, claims 26-27 of US Patent No. 11214771 in view of Nakano et al. (US10501724), Kuwahara et al. (2014), Hasegawa et al. (2016) and Kruczek (2016) is withdrawn in response to Applicant’s amendment to the claims, cancelation of claims 1 and 19 and Applicant’s arguments on p.19-20 of the response.
The rejection of claims 1 and 19 claims 1-21 of US Patent No. 12090252 (Application No. 16/647441) in view of Nakano et al. (US10501724), Kuwahara et al. (2014), Hasegawa et al. (2016) and Kruczek (2016) is moot because the claims are canceled.
Claim Rejections/Objections Maintained
In view of the amendment filed on April 7, 2025, the following rejections are maintained.
Claim Objections
7. Claims 2, 4-6, 11, 18, 20, 25 and 69-70 are objected to because of the following informalities: Claims 2, 4-6, 11, 18, 20, 25 and 69-70 depend from claim 72, which is not a preceding claim. A series of singular dependent claims is permissible in which a dependent claim refers to a preceding claim which, in turn, refers to another preceding claim.
A claim which depends from a dependent claim should not be separated by any claim which does not also depend from said dependent claim. It should be kept in mind that a dependent claim may refer to any preceding independent claim. In general, applicant's sequence will not be changed. See MPEP § 608.01(n). Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. 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, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 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 pre-AIA the applicant regards as the invention. The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 12 of the response, Applicant argues that the rejection has been overcome in view of amendment to the claims by reciting “at concentration which corresponds to 0.01nM to 0.90nM of BMP4” in claim 72 and canceling claim 1.
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§2171-MPEP§2173, the instant claims are still indefinite because of the following:
i. It is unclear what the concentration which corresponds to 0.01nM to 0.90nM of BMP4” for the claimed SHH signal transduction pathway inhibitors recited in claim 72 is. The metes and bounds of what is encompassed within the claimed “concentration which corresponds to 0.01nM to 0.90nM of BMP4” for the claimed SHH signal transduction pathway inhibitors recited in claim 72 cannot be determined. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be included and considered as “a concentration which corresponds to 0.01nM to 0.90nM of BMP4” for the claimed SHH signal transduction pathway inhibitors recited in claim 72. Thus, the claim is indefinite.
ii. Regarding claims 4 and 8, it is unclear what a concentration of dorsalization signal transmitter that does not induce expression of the claimed most dorsal markers including RPE65, MITF and COUP-TF II recited in claims is. The metes and bounds of what is encompassed within the claimed concentration recited in claims 4 and 8cannot be determined. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be included and considered as “a concentration of dorsalization signal transmitter that does not induce expression of the claimed most dorsal markers including RPE65, MITF and COUP-TF II recited in claims 4 and 8. Thus, the claims are indefinite.
iii. Regarding claims 5, 7 and 9-10, it is unclear what a concentration of dorsalization signal transmitter that promotes expression of CYP26A1 or ALDH1A1 recited in claims 5, 7 and 9-10 is. The metes and bounds of what is encompassed within the claimed concentration recited in claims 5, 7 and 9-10 cannot be determined. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be included and considered as “a concentration of dorsalization signal transmitter that promotes expression of CYP26A1 or ALDH1A1 recited in claims 5, 7 and 9-10. Thus, the claims are indefinite.
iv. Regarding claim 6, it is unclear what a concentration of dorsalization signal transmitter that does not induce expression of COUP-TFII and promoting expression of CYP26A1 and/or ALDH1A1 recited in the claim is. The metes and bounds of what is encompassed within the claimed concentration for the claimed dosralization signal transmitter recited in claim 6 cannot be determined. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be included and considered as “a concentration of dorsalization signal transmitter that does not induce expression of COUP-TFII and promoting expression of CYP26A1 and/or ALDH1A1” recited in the claim 6. Thus, the claim is indefinite.
v. Regarding claim 10, claim 10 recites both narrow and broad limitations. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitation “1.35nM BMP4”, and the claim also depends from claim 72 that recites “0.01nM-0.90nM of BMP4”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
vi. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
9. 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 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 are 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 of record and the reasons set forth below.
Claims 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 as amended encompass using a genus of concentration which corresponds to 0.01nM-0.90nM of BMP4 for the claimed SHH signal transduction pathway inhibitors recited in claim 72.
Claims 4 and 8 encompass using a genus of concentration of dorsalization signal transmitter that does not induce expression of the claimed most dorsal markers including RPE65, MITF and COUP-TF II.
Claims 5, 7 and 9-10 encompass using a genus of concentration of dorsalization signal transmitter that promotes expression of CYP26A1 or ALDH1A1.
Claim 6 encompasses using a genus of concentration of dorsalization signal transmitter that does not induce expression of COUP-TFII and promoting expression of CYP26A1 and/or ALDH1A1.
Response to Arguments
On p. 13-14 of the response, Applicant argues that the rejection has been overcome in view of amendment to claim 72 and the specification. Applicant argues that the specification provides support for the method recited in claim 7 including the limitation BMP signal transduction pathway agonist or the SHH signal transduction pathway inhibitor” and “at a concentration which corresponds to 0.01nM-0.90nM of BMP4”, and cites paragraphs [0110]-[0151], [0037], [0163] and Examples 1-2 in support of the arguments.
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 method using the claimed concentration which corresponds to 0.01nM-0.90nM of BMP4 for the claimed SHH signal transduction pathway inhibitors recited in claim 72 or the claimed genus of concentrations for not inducing expression of RPE65, MITF and COUP-TF II recited in claims 4 and 8, or for promoting expression of CYP26A1 or ALDH1A1 recited in claim 5, 7 and 9-10, or for not inducing expression of COUP-TFII and promoting expression of CYP26A1 and/or ALDH1A1 recited in claim 6 for the following reasons:
i. There is no structural and functional relationship or correlation between the claimed genus of concentration which corresponds to 0.01nM-0.90nM of BMP4 for the claimed SHH signal transduction pathway inhibitors and the concentration of 0.01nM-0.90nM of BMP4 or even the concentration of 0.15nM/0.45nM/1.35nM BMP4 used in Examples.
There is no structural and functional relationship or correlation between the claimed genus of concentration of dorsalization signal transmitter that does not induce expression of the claimed most dorsal markers including RPE65, MITF and COUP-TF II recited in claims 4 and 8 and the concentration of 0.01nM-0.90nM of BMP4 or even the concentration of 0.15nM/0.45nM/1.35nM BMP4 used in Examples.
There is no structural and functional relationship or correlation between the claimed genus of concentration of dorsalization signal transmitter that promotes expression of CYP26A1 or ALDH1A1 recited in claims 5, 7 and 9-10 and the concentration of 0.01nM-0.90nM of BMP4 or even the concentration of 0.15nM/0.45nM/1.35nM BMP4 used in Examples.
There is no structural and functional relationship or correlation between the claimed genus of concentration of dorsalization signal transmitter that does not induce expression of COUP-TFII and promote expression of CYP26A1 and/or ALDH1A1 recited in claim 6 and the concentration of 0.01nM-0.90nM of BMP4 or even the concentration of 0.15nM/0.45nM/1.35nM BMP4 used in Examples.
ii. The specification only discloses “0.15nM, 0.45nM or 1.35nM, 0.01-0.90nM BMP4” and “0.01-5mM or 0.2-1mM Cyclopamine-KAAD”.
“Compared to when a 0.15 nM BMP4 was added, when 0.45 nM or 1.35 nM BMP4 was added, the fluorescence intensity of CRX::Venus became low, which indicates that CRX::Venus-positive cell decreased… addition of a high concentration (1.35 nM) of BMP4 increases expression of ALDH1A1 gene that is expressed in the dorsalization region of a retinal tissue…. addition of a high concentration of BMP4 induces expression of ALDH1A1, promotion of differentiation of photoreceptor does not occur easily in a region with a high expression level of ALDH1A1, excessive induction of ALDH1A1 expression rather fails to promote differentiation of photoreceptor precursor” (see paragraph [0028]);
“when BMP4 at a comparatively high concentration of 0.45 nM-1.35 nM is added, expression of ALDH1A1 is excessively induced. Accordingly, a concentration at which the expression level of ALDH1A1 is preferably 30%, more preferably 15%, further more preferably not more than 10%, of that when differentiation induction is performed by adding 1.35 nM BMP4 can be determined” (see paragraph [0114]);
“when 0.15 nM BMP4 or 500 nM Cyclopamine-KAAD is added, about 60%-65% of cells express OC2) compared to that when a dorsalization signal transmitter is not added….” (see paragraph [0115]);
"BMP4 is used at a concentration of preferably 0.01 nM-0.90 nM, further preferably 0.05 nM-0.45 nM” (see paragraphs [0191]-[0193]); and
“The concentration of Cyclopamine-KAAD contained in the medium is specifically 0.01 μM-5 μM, further preferably 0.2 μM-1 μM” (see paragraph [0194]).
The specification provides no structural and functional relationship or correlation between the claimed genus of concentration which corresponds to 0.01nM-0.90nM of BMP4 for the claimed SHH signal transduction pathway inhibitors and the concentration of 0.01nM-0.90nM of BMP4 or even the concentration of 0.15nM/0.45nM/1.35nM BMP4 used in Examples.
The specification also provides no structural and functional relationship or correlation between the claimed genus of concentration that promotes expression of CYP26A1/ALDH1A1 or does not induce expression of RPE65, MITF and COUP-TF II and the concentration of 0.15nM/0.45nM/1.35nM BMP4 used in Examples or corresponding to a concentration of 0.01nM-0.90nM of BMP4.
Since the common characteristics/features of the claimed genus of concentrations and their structural and functional correlation to the conditions shown in examples 1-2 are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention in view of Zhou et al. (Development, 2015; 142:3294-3306. Doi:10.1242/dev.125385, cited previously), Kuwahara et al. (Nat. Commun. 2015;6:6286. DOI: 10.1038/ncomms7286, cited previously) and Zhong et al. (Nat. Commun.2014; 5:4047. DOI: 10.1038/ncomms5047, cited previously) because differentiation of hESCs into cone photoreceptors is agent-specific, dose-dependent and culture condition-dependent.
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 method has 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 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 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.
Double Patenting
10. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-21 of US Patent No. 12090252. The rejection is maintained for the reasons of record and the reasons set forth below. The references of Nakano et al. (US10501724), Kuwahara et al. (2014), Hasegawa et al. (2016) and Kruczek (2016) are withdrawn.
Response to Arguments
On p. 19-20 of the response, Applicant argues that the rejection has been overcome in view of amendment to the claims and the references of Nakano and Kuwahara disclose addition of BMP4 in an early developmental stage before the appearance of RX+ cells whereas the instant claims require addition of BMP4 in step (b) after an initial developmental stage wherein neural retinal progenitor cells that are RX+, PAX6+ and CHX10+ have emerged and the proportion of retinal progenitor cells that are RX+, PAX6+ and CHX10+ is not less than 30%.
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§ 804, MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. The claims 9-21 of the ‘252 patent (Application No. 16/647441) claim a method of producing a retinal tissue comprising (1) differentiating pluripotent stem cells into a retinal tissue in an initial developmental stage, and (2) culturing the retinal tissue obtained in step (1) in a first medium to obtain a retinal tissue containing a neural retinal progenitor cell and in any stage between a differentiation stage immediately after emergence of a ganglion cell and a differentiation stage where emergence rate of a cone photoreceptor precursor reaches maximum, and (3) culturing the retinal tissue in a second medium comprising a dosralization signal transmitter selected from a group consisting of BMP signal transduction pathway agonist and SHH signal transduction pathway inhibitor at a concentration that suppresses expression of a ventral marker, and wherein the neural retinal tissue comprises (i) the proportion of the number of cells of the photoreceptor precursor and photoreceptor is not less than 40% based on the total number of cells; (ii) a content of cone photoreceptor precursor and cone photoreceptor contained in photoreceptor precursor and photoreceptor is not less than 70%, and wherein the BMP signal transduction pathway agonist includes BMP4 (claim 17) and wherein the concentration includes 0.05-0.45nM (claim 18).
The method recited in the claims 9-21 of the ‘252 patent anticipate instant claims because the active steps and the materials and the results are identical and within the scope of the instant claims. Therefore, the instant claims are not patentably distinct from claims 9-21 of the ‘252 patent because instant claims 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 are anticipated by claims 9-21 of the ‘252 patent.
Accordingly, the rejection of claims 2, 4-11, 18, 20-21, 25, 69-70, 72-73 and 75-77 on the ground of nonstatutory double patenting as being unpatentable over claims 9-21 of US12090252 is maintained.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on April 7, 2025.
Claim Rejections - 35 USC § 112
11. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 10 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10 recites the limitation “1.35nM BMP4”. However, claim 10 also depends from claim 72 that recites the limitation “0.01nM-0.90nM of BMP4”, which is the narrower statement of the range/limitation. Thus, claim 10 does not further limit the subject matter of the claim upon which it depends dependent form. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
12. NO CLAIM IS ALLOWED.
13. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nakano (US10501724, cited previously) teaches methods for producing a retinal tissue and retina-related cells including retinal progenitor cells and retinal layer-specific neural cells from pluripotent stem cells, wherein the retinal tissue or retinal progenitor cells comprise cone photoreceptor precursors and cone photoreceptors, the method comprising: (1) a 1st step of subjecting PSCs to floating culture in a serum-free medium to form an aggregate of PSCs; (2) a 2nd step of subjecting the aggregated formed in 1st step to floating culture in a serum free medium containing a substance acting on the BMP signal transduction pathway from the start of floating culture in step (1) until a cell expressing RaX gene appears, thereby obtaining an aggregate containing retinal progenitor cells; (3) a 3rd step of subjecting the aggregate formed in 2nd step to floating culture in a serum free medium or serum-containing medium each being free of any of a substance acting on the BMP signal transduction pathway and a substance acting on the Wnt signal pathway, thereby obtaining an aggregate containing retinal tissue and substantially free of non-neural head ectoderm; wherein the substance acting on the BMP signal transduction pathway includes BMP4; the concentrations of the substance acting on the BMP signal transduction pathway (including BMP4) includes 0.01nM-1uM, 0.1nM-100nM or 1.5nM, and the substance acting on the BMP signal transduction pathway (including BMP4) is added at day 1-day 15 or day 1-day 9 or day 3 from the start of the floating culture and continued for at least 7 days or longer, 24 days, 26 days or 7-200 days, and wherein the cell aggregates include cell aggregates derived from RAX::GFP knock-in human embryonic stem cells (RAX::GFP hESCs) in a medium supplemented with BMP4 at 1.5nM at day 3 from the start of suspension culture, wherein the retinal tissue comprises retinal progenitor cells including photoreceptor precursor cells including CRX- expressed photoreceptor precursors and photoreceptors including RXR- expressed cone photoreceptor cells (see col. 1, 58 to col. 3, line 15; col.4, lines 21-col. 5, line 2; col. 15, lines 35-37; col. 17, lines 43-45; col. 19-24, Examples 1-7, col. 24-26, claims 1-15).
Kuwahara et al. (Nat. Commun. 2014; 6:6286. DOI:10.1038/ncomms7286, cited previously) teaches a method for increasing a proportion of a cone photoreceptor precursor and a cone photoreceptor in photoreceptor precursors and photoreceptors comprised in a retinal tissue comprising CRX+ cells, the method comprising culturing a retinal tissue in an initial developmental stage of Venus-Knock-in hESC aggregates in a medium comprising a low concentration of BMP4 starting at 1.5nM at day 6 and subject to half-dilution every 3rd day, which dramatically increased RX:Venus expression, most BMP4-induced Venus+ epithelium on day 24 are positive for RX, CHX10, PAX6 as in claim 1 (p. 2, 2nd col. ,results; p. 3-4, figures 1) and wherein the RXR- cone precursors are generated from hESC-derived neural retina (NR) (p. 12, col.1, paragraph 5).
Hasegawa (Development, 2016; 143:3895-3906, as in IDS) teaches the effects of BMP signaling in dorsal specification (see abstract) in a culturing system to control the Dorsal-Ventral (D-V) polarization of the retinal neuroepithelium (see pages 3895-3896, bridging), and that BMP4 and cyclopamine-KAAD treatment regulate D-V marker expression in mESC-derived retinal tissues (see p. 3896, right col.), and wherein cyclopamine-KAAD or hBMP4 (R&D) was applied to the aggregates in each well on day 5-6.5 or day 7-8.5 prior to the RT-qPCR assay (see p. 3905, left col: Recombinant proteins and small molecules).
Kruczek (Ph.D. Thesis, 2016, Division of Bioscience, Department of Cell and Developmental Biology, University College London, cited previously) teaches generation of cone photoreceptors from cone photoreceptor precursors from mouse embryonic stem cells (mESCs) by culturing mESCs in a retinal differentiation medium comprising MEM-HEPES, HBSS, glucose, FBS, N2-supplement, penicillin/streptomycin and L-glutamine (p. 112) from day 9-12, and then in retinal maturation medium (RMM) comprising DMEM/F12, GlutaMax, N2 supplement and penicillin/streptomycin and supplemented with retinoic acid and taurine from day 14 and then RMM supplemented with taurine from days 16-30 (p. 112 and 125). Kruczek teaches that Trb2 and RXRg are makers for early stages in cone differentiation (p. 123, first paragraph and p. 135) and the expression of Trb2 and RXRg can be detected from day 12 of differentiation, peak around day 20 of differentiation in vitro (p. 136-139).
14. 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 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