DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 11/21/2025 in response to the Restriction Requirement mailed on 10/27/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-20 are pending.
6. Applicant’s remarks filed on 11/21/2025 in response to the Restriction Requirement mailed on 10/27/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Election/Restrictions
7. Applicant’s election of Group I, claims 1-14, in the reply filed on 11/21/2025 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)).
8. Claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/21/2025.
Claims 1-14 are pending and examined on the merits.
Priority
9. Acknowledgement is made of applicants’ claimed domestic priority to U.S. Provisional Application No. 63/238415, filed on 08/30/2021.
Information Disclosure Statement
10. The IDSs filed on 03/21/2023 and 11/21/2025 have been considered by the examiner and copies of the Form PTO/SB/08 are attached to the office action.
Drawings
11. The Drawings filed on 08/17/2022 are acknowledged and accepted by the examiner.
Claim Rejections - 35 USC § 101
12. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
13. Claims 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature-based product without significantly more. Claim(s) 1-12 recite(s) a retinal organoid model system, comprising: a population of human pluripotent stem cell (hPSC)-derived photoreceptor cells, wherein the PR cells are adapted to elaborate an interphotoreceptor matrix (IPM) with visible outer segments on a surface thereof upon restoration of function of a gene encoding a structural component of the IPM. Claim(s) 13-14 recite a retinal organoid model system comprising: a population of human pluripotent stem cell (hPSC)-derived photoreceptor cells, wherein the PR cells comprise a recombinant gene encoding a structural component of an interphotoreceptor matrix (IPM), wherein the gene comprises at least one of i) a first non-functional allele comprising a first engineered genetic mutation, and/or ii) a second non-functional allele comprising a second engineered genetic mutation, and wherein restoration of function of at least one of the first and second alleles produces an IPM containing visible outer segments on a surface of the PR cells. This judicial exception is not integrated into a practical application because they read on naturally occurring human pluripotent stems cells that develop into photoreceptor cells. Although the dependent claims that recite an “induced pluripotent stem cell” carries the meaning in the art of an adult cell that has been reprogrammed to revert to its embryonic state, this is not significant enough to transform the cell into something that is markedly different from a pluripotent stem cell counterpart. Furthermore, the naturally occurring mutation recited in claim 6 encompasses natural IMPG gene mutations such as those disclosed by Bandah-Rozenfeld et al. (American Journal of Human Genetics, 2010; cited on IDS filed on 11/21/2025). Additionally, the recitation of “genetically engineered mutation” as recited in claims 6, 9, and 10 is specified at such a high degree of generality that it encompasses engineered natural mutations that would not be distinguished from its natural counterpart. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because human pluripotent stem cells derived from photoreceptor cells are naturally occurring components found in humans as evidenced by Sajurjo-Soriano et al. (WO 2020/221832 A1; cited on IDS filed 11/21/2025). Furthermore, mutations in an allele encoding an interphotoreceptor matrix such as the IPMG2 are natural mutations that occur in retinitis pigmentosa as evidenced by Bandah-Rozenfeld et al. (American Journal of Human Genetics, 2010; cited on IDS filed on 11/21/2025). The additional limitations “wherein the PR cells are adapted to elaborate an interphotoreceptor matrix with visible outer segments on a surface thereof upon restoration of function of a gene encoding a structural component of the IPM” are not sufficient to amount to significantly more than the judicial exception because the cells are not in the active process of restoration of function of a gene such as done in the methods of Sajurjo-Soriano et al. [see above]. The cells need only be capable of being modified. This language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between the natural pluripotent stem cell and its usefulness in being genetically modified. The dependent claims 3-5 and 14 only serve to further limit said correlation. Accordingly, the retinal organoid model systems of claims 1-14 are not patent eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102
14. 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.
15. Claim(s) 1-5 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Sanjurjo-Soriano et al. (WO 2020/221832 A1, priority to 04/30/2019; cited on IDS filed 11/21/2025).
16. Claims 1-5 are drawn to a retinal organoid model system, comprising: a population of human pluripotent stem cell (hPSC)-derived photoreceptor cells, wherein the PR cells are adapted to elaborate an interphotoreceptor matrix (IPM) with visible outer segments on a surface thereof upon restoration of function of a gene encoding a structural component of the IPM.
17. With respect to claims 1 and 3-5, Sajurjo-Soriano et al. teach a retinal organoid model system comprising a population of human pluripotent stem cells derived photoreceptor cells genetically modified for the treatment of inherited retinal dystrophies [see Abstract; p. 4; p. 23, bottom]. The specification defines the term “elaborate” to mean “develop, express, or display”. Although Sajurjo-Soriano et al. does not explicitly teach “wherein the PR cells are adapted to elaborate an interphotoreceptor matrix (IPM) with visible outer segments on a surface thereof upon restoration of function of a gene encoding a structural component of the IPM”, the cells are not in the active process of restoration of function of a gene such as done in the methods of Sajurjo-Soriano et al. [see above]. The cells need only be capable of being modified, and it is the examiner’s position that interphotoreceptor matrix is inherent to the human pluripotent stem cells derived from photoreceptor cells taught by Sajurjo-Soriano et al. This language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between the natural pluripotent stem cell and its usefulness in being genetically modified. The dependent claims 3-5 only serve to further limit said correlation. Nevertheless, Sajurjo-Soriano et al. teach restoration of a genetic mutation by administration of a therapeutic comprising a viral particle and an RNA editor such as CRISPR [see Abstract; p. 2; p. 26, bottom].
With respect to claim 2, Sajurjo-Soriano et al. teach the retinal organoid model system, wherein the hPSC is a human induced pluripotent stem cell [see p. 3, top].
Claim Rejections - 35 USC § 103
18. 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, 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.
19. Claim(s) 6-7 and 11-14 is/are rejected under 35 U.S.C. 103 as being unpatentable Sanjurjo-Soriano et al. (WO 2020/221832 A1, priority to 04/30/2019; cited on IDS filed 11/21/2025) in view of Bandah-Rozenfeld et al. (American Journal of Human Genetics, 2010; cited on IDS filed on 11/21/2025).
20. The relevant teachings of Sanjurjo-Soriano et al. as applied to claims 1-5 are set forth in the 102(a)(1) and 102(a)(2) rejection above.
With respect to claims 6-7 and 11-14, Sajurjo-Soriano et al. teach a retinal organoid model system comprising a population of human pluripotent stem cells derived photoreceptor cells genetically modified for the treatment of inherited retinal dystrophies [see Abstract; p. 4; p. 23, bottom]. Sajurjo-Soriano et al. teach restoration of a genetic mutation by administration of a therapeutic comprising a viral particle and an RNA editor such as CRISPR [see Abstract; p. 2; p. 26, bottom].
With respect to claim 6, Sajurjo-Soriano et al. teach the retinal organoid system wherein the hPSC is a patient derived hiPSC comprising a naturally occurring mutation in gene [see p. 3].
With respect to claim 7, Sajurjo-Soriano et al. teach the retinal organoid system wherein the mutation is a coding mutation [see p. 3].
With respect to claim 13, Sajurjo-Soriano et al. teach wherein the gene comprises a first and second non-functional allele [see p. 7].
However, Sajurjo-Soriano et al. does not teach the retinal organoid model system of claim 6, comprising a mutation in a gene encoding a structural component of the IPM or mutation in at least one allele in the gene encoding a structural component of the IPM; the retinal organoid model system of claim 11, wherein the gene encoding a structural component of the IPM is IMPG1 or IMPG2; the retinal organoid model system of claim 12, wherein the gene encoding a structural component of the IPM is IMPG2; and the retinal organoid model system of claim 13, comprising a recombinant gene encoding a structural component of an interphotoreceptor matrix.
Bandah-Rozenfeld et al. teach mutation analysis of cases of autosomal recessive retinitis pigmentosa reveals four nonsense and one missense mutation affecting a highly conserved phenyalanine reside in IMPG2 that encodes the interphotoreceptor matrix proteoglycan IMPG2, a constituent of the interphotoreceptor matrix, leading to autosomal recessive retinitis pigmentosa [see Abstract; p. 201 column 2 to p. 202].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Sajurjo-Soriano et al. and Bandah-Rozenfeld et al. to develop a retinal organoid model system for the restoration of the function of a IMPG2 of the IPM because Sajurjo-Soriano et al. teach a retinal organoid model system comprising a population of human pluripotent stem cells derived photoreceptor cells genetically modified for the treatment of inherited retinal dystrophies [see Abstract; p. 4; p. 23, bottom]. Bandah-Rozenfeld et al. teach four nonsense and one missense mutation in the IMPG2 encoding IMPG2 of the IPM of retinal cells leads to autosomal recessive retinitis pigmentosa. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would have been motivated to combine the teachings of Sajurjo-Soriano et al. and Bandah-Rozenfeld et al. because Bandah-Rozenfeld et al. acknowledges four nonsense and one missense mutation in the IMPG2 encoding IMPG2 of the IPM of retinal cells leads to autosomal recessive retinitis pigmentosa and one would have a reasonable level of predictability that the systems of Sajurjo-Soriano et al. could be modified to target and correct the IMPG2 mutations using the therapeutic system taught by Sajurjo-Soriano et al. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
21. Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable Sanjurjo-Soriano et al. (WO 2020/221832 A1, priority to 04/30/2019; cited on IDS filed 11/21/2025) in view of Bandah-Rozenfeld et al. (American Journal of Human Genetics, 2010; cited on IDS filed on 11/21/2025) and Strulovici et al. (Molecular Therapy, 2007; examiner cited).
22. The relevant teachings of Sanjurjo-Soriano et al. as applied to claims 1-5 are set forth in the 102(a)(1) and 102(a)(2) rejection above.
With respect to claims 8-10, Sajurjo-Soriano et al. teach a retinal organoid model system comprising a population of human pluripotent stem cells derived photoreceptor cells genetically modified for the treatment of inherited retinal dystrophies [see Abstract; p. 4; p. 23, bottom]. Sajurjo-Soriano et al. teach restoration of a genetic mutation by administration of a therapeutic comprising a viral particle and an RNA editor such as CRISPR [see Abstract; p. 2; p. 26, bottom]. Sajurjo-Soriano et al. teach the retinal organoid system wherein the mutation is a coding mutation [see p. 3].
However, Sajurjo-Soriano et al. does not teach the retinal organoid model system of claim 8, wherein the hPSC is a hESC selected from the group consisting of H9, H1, H7, BG01, HES-3, HES-2, HSF-6, HUES9, HUES7, and I6 and the retinal organoid system of claim 9, comprising a mutation in at least one allele in the gene encoding a structural component of the IPM.
Bandah-Rozenfeld et al. teach mutation analysis of cases of autosomal recessive retinitis pigmentosa reveals four nonsense and one missense mutation affecting a highly conserved phenyalanine reside in IMPG2 that encodes the interphotoreceptor matrix proteoglycan IMPG2, a constituent of the interphotoreceptor matrix, leading to autosomal recessive retinitis pigmentosa [see Abstract; p. 201 column 2 to p. 202].
Strulovici et al. teach that hESCs represent an unlimited supply of normal differentiated cells to engineered disease tissues to regain normal function and can be useful as human therapeutics [see Abstract; p .850; Figure 1] and teach hESCs that can be genetically modified such as H9, H1, H7, and HES [see Table 4].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Sajurjo-Soriano et al., Bandah-Rozenfeld et al., and Strulovici et al. to develop a retinal organoid model system for the restoration of the function of a IMPG2 of the IPM in hESCs because Sajurjo-Soriano et al. teach a retinal organoid model system comprising a population of human pluripotent stem cells derived photoreceptor cells genetically modified for the treatment of inherited retinal dystrophies [see Abstract; p. 4; p. 23, bottom]. Bandah-Rozenfeld et al. teach four nonsense and one missense mutation in the IMPG2 encoding IMPG2 of the IPM of retinal cells leads to autosomal recessive retinitis pigmentosa. Strulovici et al. teach that hESCs represent an unlimited supply of normal differentiated cells to engineered disease tissues to regain normal function and can be useful as human therapeutics. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would have been motivated to combine the teachings of Sajurjo-Soriano et al. and Bandah-Rozenfeld et al. because Bandah-Rozenfeld et al. acknowledges four nonsense and one missense mutation in the IMPG2 encoding IMPG2 of the IPM of retinal cells leads to autosomal recessive retinitis pigmentosa and Strulovici et al. acknowledges that hESCs represent an unlimited supply of normal differentiated cells to engineered disease tissues to regain normal function and can be useful as human therapeutics. One would have a reasonable level of predictability that the systems of Sajurjo-Soriano et al. could be modified to target and correct the IMPG2 mutations using the therapeutic system taught by Sajurjo-Soriano et al. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
23. Status of the claims:
Claims 1-20 are pending.
Claims 15-20 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-14 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656