DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 6/2/2026.
Claims 1, 2, 4-15, 17, 21, 22, 24 and 26 are pending.
This application is a continuation of International Application Serial Number PCT/US2022/015280, filed February 4, 2022 which claims priority to U.S. Provisional Application No. 63/145,981, filed February 4, 2021.
Response to Amendments
Applicants submission of drawings is sufficient to overcome the objections to Figure 5N. The petition filed 6/2/2026 for color drawings has been received and a decision forthcoming.
The amendments combined with applicants provision of their definition of low MOI is sufficient to overcome the rejections under 35 USC 112b.
Applicants arguments are sufficient to overcome the rejection under 35 USC 112, second paragraph. As to the rejection under 35 USC 112, first, some of the issues were not addressed by applicants arguments and amendments and stand.
The Declaration filed 6/2/2026 is sufficient to overcome the rejection under 35 USC 102 and 103 by establishing that the prior art is based upon applicants own publication.
It is noted that a call was made to amend the claims but the time frame in which the case was required to be completed did not allow for a conversation.
Claim Rejections - 35 USC § 112, first paragraph
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.
Claims 11 and 12 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. Applicants have not addressed these rejections.
The instant claims are drawn to an in vitro model of Alzheimer’s disease (AD) the model comprising hiNSCs infected with a low multiplicity of infection of HSV-1. The hiNSC cells were well known in the art and could be formed easily and quickly from somatic cells using traditional differentiation methods (see Erharter abstract and page 3354, col 2). This model is developed by applicants to meet the need for human models wherein hiNSC mimics brain tissue. HSV-1 infection is performed due to the implication that it is a potential causative agent.
The population of cells acting as an in vitro model of AD are broadly and incompletely claimed. First, claim 11 recites that the starting cells prior to differentiation into hiNSC are somatic cells from a patient with or at risk of developing AD. As to cells from patients at risk of developing AD, the disclosure does not identify those patient cells. The risk of developing AF is only provided as potential aging which and HSV infection, but neither provide the proper structure according to the disclosure to meet this cell type. This does not allow one to identify the cells necessary to use that are from a patient at risk of AD. Without the functional properties, the claim is directed to a desired cell.
Secondly, claim 12 refers to cells with AD-like phenotypes. Phenotypes of AD are provided for and include
[0047] Thus, in some embodiments, the HSV-1 infected hiNSCs within the models exhibit (a) large, multicellular, dense Aβ+ fibrillar plaque-like formations (PLFs), (b) expression of PSEN1 and PSEN2 at higher levels as compared to non-infected control cells, (c) reactive gliosis, (d) one or more indicators of neuroinflammation, or (e) one or more of (a)-(d). Further, in some embodiments, the HSV-1 infected hiNSCs have a transcriptomic signature with increased or decreased level of relative expression levels of different genes as demonstrated in FIG. 9.
[0048] Aβ+ fibrillar plaque-like formations (PLFs) can be monitored visually or optically. As described in the examples, suitable methods to visually plaque size include, for example, fluorescent dye labeling of the HSV-1 infected hiNSCs, and monitoring and tracking size of amyloid plaques over time. One suitable dye is Thioflavin T dye, but other suitable dyes are known and understood in the art. One suitable tracking system include Incucyte Live-Cell analysis system (Sartorius) but other equivalent systems may also be used. Further, the genetically modified hiNSCs described herein that express one or more reporter gene may be used to monitor PLF formation without additional dyes or reagents.
[0049] Another characteristic of the AD-like phenotype, includes the enlargement, blebbing and fusion of nuclei to form these multicellular plaques. Suitably, this can be monitored by methods known in the art, including the use of a nuclear dye, preferably a fluorescent nuclear dye, and the real time monitoring and quantification of abnormal nuclei vs normal nuclei within the AD-model culture. The reduced number of healthy normal-sized nuclei would be indicative of abnormal AD-like phenotype.
[0050] Another AD-phenotype characteristic includes the increased expression of PSEN1 and PSEN2, which are associated with AD development. PSEN1 and PSEN2 overexpression is thought to play an important role in the generation of amyloid beta from amyloid precursor protein (APP), the accumulation of amyloid beta is associate with AD-phenotype. Suitable methods of detecting and monitoring expression of PSEN1 and PSEN2 within cells of the AD-model described herein are known and understood in the art, including, immunohistochemical staining, flow cytometry, PCR, qPCR, western blot, among others, and as demonstrated in the examples. Suitably, the AD-phenotype is characterized by an increase expression of PSEN1, PSEN2 or both when compared to hiNSCs not infected with the HSV virus (non-infected control cells).
However, there is no clear description of AD-like phenotypes.
Because the disclosure does not provide the relevant properties to identify the person at risk or AD-like phenotypes, these is a limited descriptive element wherein the claims broadly and incompletely claim the inventive elements and one cannot from the limited disclosure envision the large genus of the claims. The claims lack adequate description to link structure to these required functions. The Court indicated that while applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a precise definition of a representative number of members of the genus, such as by reciting the structure. Structural features that could distinguish the compounds of the claimed genus from others not encompassed by the genus are missing from the disclosure. In this case, there are specific elements referenced but the claims reference these structures with broad generic functional terms that represent a large and diverse genus of elements.
Conclusion
Claims dependent on claim 12 have been indicated as objected to as dependent on a rejected claim but would be allowable if drafted into independent form.
THIS ACTION IS MADE FINAL. 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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634
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