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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/01/2026 has been entered.
Status of the Claims
Claims 3-6, 10-12, 14, 16-18, 22, and 24-26 are currently pending.
Claims 12 and 26 are amended.
Claims 1-2, 7-9, 13, 15, 19-21, and 23 are cancelled.
Claims 3-6, 10-12, 14, 16-18, 21-22, and 24-26 have been considered on the merits.
Claim Rejections - 35 USC § 102
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 3-6, 10-12, 14, 16-17, and 24-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rabesandratana et al (Frontiers, 2020)(reference of record), as evidenced by Langer et al (Stem Cell Reports, 2018) and Sluch et al (Scientific reports, 2015).
Claim Interpretation: Claims 12 and 25 recite the limitation that the iPSCs are differentiated into RGCs without genetic modification. Support for this is found in the specification at pg. 13, para 3-4. Paragraph 3 of pg. 13 states that the iPSCs are differentiated from iPSCs to RGCs without any genetic modifications. Paragraph 4 of pg. 13 states that the “RGCs developed in accordance with the invention can be used to express transgenes of interest to assess their effects on RGC viability and function”. Therefore, the phrase “without genetic modification” is being interpreted to only apply to the differentiation protocol between iPSCs and RGCs and does not apply to expression of transgenes which do not aid in differentiation but only provide a means of visibility for assessment. Additionally, this differentiation protocol between the iPSC and RGC step has been previously interpreted as a product by process limitation, and therefore the phrase “without genetic modification” is also being interpreted as a product-by process limitation which is met by the product of the prior art.
With regards to claim 12, Rabesandratana teaches a method for the treatment of an ocular disorder comprising administering a therapeutically effective amount of a population of purified retinal ganglion cells (RGCs) (pg. 5, column 1, para 1). The RGCs are administered in a pharmaceutically acceptable carrier (pg. 5, column 1, para 1). Rabesandratana teaches that the RGCs express BRN3A (pg. 5, col. 1, last para), TUBB3 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3), CD90 (aka. THY1, pg. 2, col. 1, last para), RBPMS (pg. 5, col. 2, para 1) and TUJ1 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3).
With regards to claim 14, the cells were administered by intravitreal injection (pg. 5, column 1, para 1).
Regarding claim 17, the RGCs are sorted using flow cytometry as well as magnetic activated cell sorting (MACS) (pg. 3, column 2, para 1 and 2).
Regarding claim 5, Rabesandratana teaches that the RGCs express BRN3A (pg. 5, col. 1, last para), TUBB3 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3), CD90 (aka. THY1, pg. 2, col. 1, last para), RBPMS (pg. 5, col. 2, para 1) and TUJ1 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3).
Regarding claim 24, Rabesandratana teaches that the RGCs express BRN3A (pg. 5, col. 1, last para).
Rabesandratana meets the limitations of the disorder being selected from glaucoma, age-related macular degeneration (AMD), a disorder related to an increase in intraocular pressure (IOP), a disorder related to neuroprotection or diabetic retinopathy as evidenced by Tang et al. Tang teaches that the optic nerve crush model, employed in Rabesandratana, is a model for traumatic optic neuropathy and glaucoma as required by claims 12 (abstract, para 2).
Rabesandratana meets the limitations of the RGCs co-expressing BRN3A, BRN3B, CD90, MAP2, RBPMS, and TUJ1 markers as required by claims 5 and 12 as evidenced by Sluch et al. In regards to this limitations, Rabesandratana explicitly teaches that the RGCs co-express BRN3A (pg. 5, col. 1, last para), CD90 (aka. THY1, pg. 2, col. 1, last para), RBPMS (pg. 5, col. 2, para 1) and TUJ1 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3). Rabesandratana does not test the population of RGCs for the expression of BRN3B and MAP2. However, Sluch demonstrates a population of RGCs which co-express all of the claimed markers including those already demonstrated in Rabesandratana. Sluch demonstrates an RGC population described as having “stained positive for the mCherry protein, the general neuronal markers TUJ1, MAP2, and NEUN, and the more RGC-enriched markers BRN3B, BRN3A, NEFH, PAX6, THY1, RBPMS, ISL1, and SNCG” (see Fig. 5 description; also Fig. 2).
Rabesandratana meets the limitations of the RGCs including at least one expression marker selected from CALB2, MMP17, FSTL4, and SPP1 as required by claim 22 as evidenced by Langer et al. Langer teaches that of a population of RGCs which express the BRN3 proteins, about 30% express FSTL4 (pg. 1284, col. 2, para 1) and about 21% express SPP1 (pg. 1285, col. 1, para 2) as required by claim 22. Rabesandratana teaches that the RGCs express BRN3A (pg. 5, col. 1, last para). Therefore, Langer teaches that a population of BRN3-positive cells will contain multiple expression marker of RGCs including FSTL4 and SPP1 as required by claim 22.
Claims 3-4, 6, 10-12, 16, and 25 are product by process claims or contain product by process limitations in which the process of making/differentiating the RGCs carries little patentable weight. Please see MPEP 2113. It is only the product, which is anticipated by the prior art and not the process by which the product was made. This is because the final product (RGCs) is not distinguished by any particular features or characteristics resulting from the process by which it was made. As such, the limitations of the claimed process of differentiating the RGCs is met by any process of differentiating RGCs in the prior art. Patentability of a product-by-process claim is determined by the novelty and nonobviousness of the claimed product itself without consideration of the process for making it which are encompassed by the claimed process of differentiating the RGCs of claims 3-4, 6, 10-12, 16, and 25. Thus, the teachings of Rabesandratana anticipate the limitations of claims 3-4, 6, 10-12, 16, and 25.
Claim 26 contains a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claim 12 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, Rabesandratana anticipates the claims.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Rabesandratana et al (Frontiers, 2020; reference of record), as evidenced by Langer et al (Stem Cell Reports, 2018; reference of record) and Sluch et al (Scientific reports, 2015; reference of record), as applied to claims 3-6, 10-12, 14, 16-17, and 21-25 above, and in further view of Miltenyi Biotech (CD90.2 MicroBeads, Mouse; Wayback Machine 2021) (reference of record).
With regards to claim 18, the independent limitations are taught above by Rabesandratana. Rabesandratana teaches the use of MACS with THY1 (CD90) antibody and anti-mouse IgG1 MicroBeads (pg. 3 column 1, para 1). THY1 is also known as CD90 therefore the population of RGCs is CD90+ (pg. 2, column 1, para 3).
Rabesandratana does not teach the use of CD90.2 magnetic beads to perform the CD90+ sorting.
However, Miltenyi Biotec teaches that the CD90.2 Microbeads were developed for the selection or depletion of mouse cells (overview). Since Rabesandratana teaches the selection of human RGCs using CD90 it would be obvious to one of ordinary skill in the art to select the most appropriate CD90 selection beads for the species of cell being sorted.
One of ordinary skill in the art would find it obvious at the effective filling date to combine the method RGC selection method taught by Rabesandratana with the CD90.2 MicroBeads taught by Miltenyi Biotec to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Rabesandratana teaches that THY1 is also known as CD90 (pg. 2, column 1, para 3) and that Miltenyi Biotec teaches that the CD90.2 Microbeads were developed for the specific selection or depletion of mouse cells (overview). One of ordinary skill in the art would have a reasonable expectation of success when combining because applying the beads developed for the specific species of cell being used is well known practice in the art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Rabesandratana et al (Frontiers, 2020; reference of record), as evidenced by Langer et al (Stem Cell Reports, 2018; reference of record) and Sluch et al (Scientific reports, 2015; reference of record), as applied to claims 3-6, 10-12, 14, 16-17, and 21-25 above, and in further view of Nasonkin et al (US20200368394 A1).
With regards to claim 26, the limitations of the independent claim are taught above by Rabesandratana.
Rabesandratana does not teach administration without an immunosuppressive regimen as required by claim 26.
However, Nasonkin teaches about grafts comprising stem cell derived RGCs which are used to treat retinal damage from retinal degenerative diseases such as AMD (abstract; [0003]).
Regarding claim 26, Nasonkin teaches that the therapeutic cell composition can be administered with or without an immunosuppressive regimen ([0220]).
Further, Nasonkin teaches that 3-6 months after retinal graft, about 80% of subjects have retinal cells surviving ([0215]).
Claim 26 contains a wherein clause that recites the intended result of the method, which is a transplantation rate of 94%, rather than requiring an additional step be performed. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claim 12 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
One of ordinary skill in the art would find it obvious at the effective filling date to combine the RGC grafting method taught by Rabesandratana with the RGC grafting method which does not utilize an immunosuppressive regimen taught by Nasonkin to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because both Rabesandratana and Nasonkin demonstrate similar methods of administering RGCs to the retina and Nasonkin achieves a higher transplantation rate than Rabesandratana of 80% after 3-6 months, which is a substantial time frame. Further, Nasonkin teaches that the eye is a small, encapsulated organ, with immune privilege ([0007]). One of ordinary skill in the art would have a reasonable expectation of success when combining Rabesandratana and Nasonkin because both teach a similar method of administering RGCs to an eye in need thereof due to retinal degeneration.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 09/12/2025 have been fully considered and the following arguments are found persuasive.
Applicant argues (Remarks, pg. 7, para 4), in regards to the rejection of claim 26 under 35 U.S.C. 102, that the RGCs of the Rabesandratana do not demonstrate the result of 94% transplantation rate without an immunosuppressive regimen.
In response, this argument is found persuasive. The amendments made onto claim 26 requiring the limitation of being administered without an immunosuppressive regimen have required the withdrawal of the rejection made onto claim 26. Claim 26 is now rejected under 35 U.S.C. 103 by Rabesandratana in view of Nasonkin.
Applicant's arguments filed 09/12/2025 have been fully considered but the following arguments have been found non-persuasive.
Applicant argues (Remarks, pg. 8, para 1-3) that the product by process limitations of forming the RGCs recited in claim 12 “yields a distinct product” that have distinctive characteristics not present in the RGCs taught by Rabesandratana, nor the evidentiary references Langer and Sluch.
In response, this argument is not found persuasive. Rabesandratana meets the limitations of the RGCs co-expressing BRN3A, BRN3B, CD90, MAP2, RBPMS, and TUJ1 markers as required by claims 5 and 12 as evidenced by Sluch et al. In regards to this limitations, Rabesandratana explicitly teaches that the RGCs co-express BRN3A (pg. 5, col. 1, last para), CD90 (aka. THY1, pg. 2, col. 1, last para), RBPMS (pg. 5, col. 2, para 1) and TUJ1 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3). Rabesandratana does not test the population of RGCs for the expression of BRN3B and MAP2. However, Sluch demonstrates a population of RGCs which co-express all of the claimed markers including those already demonstrated in Rabesandratana. Sluch demonstrates an RGC population described as having “stained positive for the mCherry protein, the general neuronal markers TUJ1, MAP2, and NEUN, and the more RGC-enriched markers BRN3B, BRN3A, NEFH, PAX6, THY1, RBPMS, ISL1, and SNCG” (see Fig. 5 description; also Fig. 2). Therefore, the characteristics of the RGCs claimed by applicant do not appear to be a distinct product over the art and the product-by-process limitations do not appear to impart a distinct product. Therefore, the argument is not found persuasive.
Applicant argues (Remarks, pg. 9) that Miltenyi Biotech fails to remedy the alleged deficiencies of Rabesandratana.
In response, this argument is not found persuasive because the alleged deficiencies have been addressed at point 18 above.
Applicant argues (Remarks, pg. 10-13) that the amendments made onto claim 12, including the recitation of 2D culture implies a structural difference on the cells which is that the RGC population co-expresses BRN3A, BRN3B, CD90, MAP2, RBPMS, and TUJ1, which Applicant asserts the cited art fails to identify. Applicant argues that Rabesandratana only demonstrates THY1 (CD90) RGC selection.
In response, this argument is not found persuasive. The recitation of 2D culture is a product-by-process limitation in which the process of making/differentiating the RGCs carries little patentable weight. Please see MPEP 2113. It is only the product, which is anticipated by the prior art and not the process by which the product was made. This is because the final product (RGCs) is not distinguished by any particular features or characteristics resulting from the process by which it was made. As such, the limitations of the claimed process of differentiating the RGCs is met by any process of differentiating RGCs in the prior art. Patentability of a product-by-process claim is determined by the novelty and nonobviousness of the claimed product itself without consideration of the process for making it which are encompassed by the claimed process of differentiating the RGCs.
Further, Rabesandratana meets the limitations of the RGCs co-expressing BRN3A, BRN3B, CD90, MAP2, RBPMS, and TUJ1 markers as required by claims 5 and 12 as evidenced by Sluch et al. In regards to this limitations, Rabesandratana explicitly teaches that the RGCs co-express BRN3A (pg. 5, col. 1, last para), CD90 (aka. THY1, pg. 2, col. 1, last para), RBPMS (pg. 5, col. 2, para 1) and TUJ1 (aka. Beta-III-tubulin, pg. 5, col. 2, para 3). Although the cells of Rabesandratana are sorted for THY1, Rabesandratana demonstrates that the THY1/CD90 positive cell population is also positive for BRN3A, RBPMS, and TUJ1. Rabesandratana does not test the population of RGCs for the expression of BRN3B and MAP2. However, Sluch demonstrates a population of RGCs which co-express all of the claimed markers including those already demonstrated in Rabesandratana. Sluch demonstrates an RGC population described as having “stained positive for the mCherry protein, the general neuronal markers TUJ1, MAP2, and NEUN, and the more RGC-enriched markers BRN3B, BRN3A, NEFH, PAX6, THY1, RBPMS, ISL1, and SNCG” (see Fig. 5 description; also Fig. 2). Therefore, the argument is not found persuasive.
Conclusion
No claims are allowed.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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