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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed April 10, 2026.
Claims 1-12, 14-24, and 27-32 are pending in the application.
Claims 1-12 and 14-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/17/2025. No claims have been canceled, amended or newly added.
Claims 24 and 28-29 have been amended, claim 25 has been canceled and claim 32 has been newly added as set forth in the claim set filed 04/10/2026.
The examiner acknowledges receiving an executed Declaration under 37 C.F.R. § 1.132 executed by Dr. Steven A. Goldman on April 7, 2026 (“Goldman Declaration”), and filed on 04/10/2026.
Therefore, claims 24 and 27-32 are examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed provisional application 63/378,092 filed 10/03/2022 and 63/274,763 filed 11/02/2021under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Thus, the earliest possible priority for the instant application is November 02, 2021.
Response to arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112 (b)
The rejection of claims 24-25 and 27-31 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second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn.
Applicant’s arguments and amendments filed 04/10/2025 have been considered and are persuasive in light of the amendments made to remove “and/or”, cancel claim 25, correct claim 28 and remove “specifically.”
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claims 24 and 27-31 remain rejected and claim 32 is newly rejected under 35 U.S.C. 103 as being unpatentable over Pol (Experimental Neurology, Volume 247, September 2013, Pages 694-702) in view of Ye (Nature Neuroscience volume 12, pages 829–838 (2009); IDS Reference) as evidenced by Megason (Development (2002) 129 (9): 2087–2098) and Zhang (Feb 2021, The Journal of Neuroscience, 41(8):1650–1664; IDS Reference) and Slutsky (Vol. 278, No. 11, Issue of March 14, pp. 8960–8968, 2003)
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 04/10/2025.
Regarding claims 24 and 32, Pol teaches a lentiviral vector comprising a nucleic acid molecule for a gene SOX10-MCS5 glial cell specific enhancer, which directs reporter expression to oligodendrocyte lineage cells in mouse and zebrafish (i.e. enhancer for a gene selectively or specifically expressed by glial progenitor cells) which dynamically identifies live human oligodendrocyte precursor cells (OPCs). Pol teaches Sox10-MCS5 reporter GFP expression in human fetal brain cells (Abstract, Fig 1a).
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However, Pol does not teach a nucleic acid molecule encoding the TCF7L2.
Ye teaches an expression vector called pCIG comprising a gene construct which has a nucleic acid molecule encoding a transcription factor 7-like 2 protein (TCF7L2; TCF4) (Online Methods). As evidenced by Fig 1a of Megason (reference 50 of Ye) below, the pCIG expression vector comprises a beta actin promoter.
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Ye further identifies TCF7L2 as being an oligodendrocyte lineage–specific transcription factor and Pdgfra and NG2 as oligodendrocyte precursor cell (OPC) markers (p. 837, 1st column; p. 830, 2nd column). The instant specification describes examples of glial precursor cells as oligodendrocyte precursor/progenitor cells (para. 0070).
Moreover, Zhang teaches promoting oligodendrocyte (OL) differentiation represents a promising option for remyelination therapy for treating the demyelinating disease multiple sclerosis (MS) and that TCF7L2 has a mechanism which promotes OL differentiation by repressing autocrine BMP4 signaling. (Abstract, p. 1650)
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to substitute a nucleic acid encoding TCF7L2 as taught by Ye for nucleic acid encoding a GFP of Pol with a reasonable expectation of success. An artisan would have been motivated to do so as Ye and Zhang teach that expression of TCF7L2 promotes OL differentiation which leads to a promising option for remyelination therapy and Pol discloses the SOX10-MCS5 enhancer that tracks differentiation of human oligodendrocyte precursor cells (OPCs) into myelinating human oligodendrocytes.
However, Pol, Ye, and Zhang do not teach wherein the promoter is a glial cell specific promoter.
Slutsky teaches the induction of SOX10 with MPB promoter constructs (i.e. glial cell specific promoter for a gene) (Abstract). MPB is known in the art as a glial specific promoter (p. 8960).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize a MPB promoter with the constructs of Pol, Ye, and Zhang in order to express TCF7L2 in glial cells with a reasonable expectation of success. Pol utilizes a SOX10 enhancer and Slutsky utilizes a promoter which expresses SOX10, thus an artisan would be motivated to utilize the two, MPB promoter and SOX10 enhancer, in the same construct. Moreover, as Pol teaches expression in glial cells such as oligodendrocytes, an artisan would be motivated to utilize promoters which target said glial cells such as MPB.
Regarding claims 27 and 28, the combination of Pol, Ye, Zhang and Slutsky render obvious claim 24. Moreover, Pol teaches the vector utilized is a lentiviral vector (Abstract, Fig 1a).
Regarding claims 29 and 30, the combination of Pol, Ye and Zhang render obvious claim 24. The limitation of “administered to a subject with a glial progenitor cell-targeted fusogen or a glial cell progenitor cell-selective surface binding moiety” is an intended use or purpose for the construct. For product claims, intended purpose/use does not provide patentable weight unless it provides any structure limitation. See MPEP2111.02
Regarding claims 31, the combination of Pol, Ye and Zhang render obvious claim 24. Moreover, Pol teaches the vector within OPCs (i.e. host cell, see instant specification para. 105) (Abstract, Fig 1a).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
In response to Applicant’s arguments and the Goldman Declaration against the 103 rejection previously set forth,
The Goldman Declaration under 37 CFR 1.132 filed 04/10/2025 is insufficient to overcome the 103 rejection as set forth in the last Office action because:
The Declaration is directed towards unexpected results which are directly correlated to a method of use and not unexpected results of the construct itself. While it can be appreciated that the remylenation effects have not previously been found in vivo, this is a use of a specific construct. Moreover, the construct claimed is much broader than that of the construct utilized as “glial specific promoter” which encodes for a gene is much broader than the promoter utilize in the specific construct found in the Examples of the specification. Thus, in contrast to applicants’ arguments the claimed construct does not require glial overexpression of TCF7L2 for significant upregulation of genes involved in myelination or lipid metabolism.
Applicant’s arguments and amendments filed 04/10/2026 have been considered however they are not persuasive.
Applicant argues that SOX10-MCS5 reporter with TCFL72 defeats the purpose of the system which is tracking OPCs, as TCFL72 could disrupt the process that Pol aims to monitor.
Applicant argues that Ye is entirely silent to a glial cell specific promoter.
Examiner agrees that the newly amended limitation was not previously provided for, now Slutsky in the new rejection above addresses the promoter limitation.
Moreover, test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Applicant argues that Megason is completely silent with respect to TCFL72.
Examiner states that Megason is only an evidentiary reference to discuss the construct of Ye.
Applicant argues that Zhang utilizes a ubiquitous promoter and not a glial cell specific promoter.
Examiner agrees that the newly amended limitation was not previously provided for, now Slutsky in the new rejection above addresses the promoter limitation.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that in light of the Declaration submitted and the specification that unexpected results regarding the in vivo effects of the construct are exhibited.
Examiner states that if the results were unexpected, it is due to a method of treatment utilizing the construct and that the construct itself is not unexpected. Moreover, the construct is not in commensurate with the scope of said unexpected results as the construct claimed is much broader than what is utilized in the Examples and specification.
Conclusion
No claims are 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 ALEXANDRA CONNORS whose telephone number is (571)272-7010. The examiner can normally be reached Monday - Friday (9AM-5PM).
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/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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