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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/17/2026 has been entered.
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 .
Status of the Claims
Claims 34-35 are pending (claim set as filed on 09/13/2024).
Priority
This application filed on 06/22/2016 is a 371 of PCT/US2015/010066 filed on 01/02/2015, which has a provisional application no. 61/923,373 filed on 01/03/2014.
Maintained Rejections
Claim Rejections - 35 USC §102, Anticipation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 34-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chirila (WO 2012/155051 A1 - cited in the IDS filed on 10/04/2016).
Chirila’s general disclosure relates to methods of diagnosing Alzheimer’s disease based on quantitatively measured complexity of skin-sampled fibroblast networks (see abstract & ¶ [002], [005]).
Regarding the independent claim, Chirila teaches “A method of diagnosing Alzheimer’s disease in a subject, the method comprising:
(a) obtaining two samples of fibroblast skin cells from the subject;
(b) treating one of the cell samples with an amyloid beta peptide (Aβ);
(c) culturing each of the Aβ-treated and untreated cell samples in a culture medium;
(d) imaging each of the Aβ -treated and untreated cell samples to obtain at least one image of each sample;
(e) analyzing the at least one image of each sample by at least one morphological analysis method relative to a control known to have Alzheimer’s Disease (AD); and
(f) diagnosing the subject based on the analysis of step (e), wherein if both of the Aβ-treated and untreated cell samples have an AD-like phenotype, the diagnosis is positive for AD, and if the Aβ -treated cell sample has an AD-like phenotype and the untreated cell sample does not, the diagnosis is negative for AD” (see page 32, claim 1, and ¶ [069], [074]: Example 1).
Regarding the aggregation, Chirila further teaches wherein step (e) comprises determining cell aggregation characteristics chosen from the existence of large aggregates, the attachment of cells to aggregates, evidence of aggregates growing, the density of aggregates (number per unit area), appearance of edges within aggregate networks (see page 32: claims 2-3). Chirila teaches Fig. 4 shows precision in the determination of average aggregate area per number of aggregates and Fig. 4B plots the area per number of aggregates as a function of initial cell density, showing an exponential relationship (solid lines) with a steeper rise for AD than for age-matched control (AC) (i.e. the cell aggregation rate with respect to rate of change as a function of density as compared to a non-Alzheimer’s disease standard by slope evaluation) (see ¶ [009], [084]-[089]).
Regarding the culturing time period, Chirila teaches culturing the Aβ-treated and untreated cell samples from about 24 hours to about 48 hours (see claim 14 and ¶ [007]).
Chirila teaches the culture medium comprises a preparation rich in extracellular matrix (ECM) proteins and further comprises at least one of laminin, collagen IV, heparin sulfate proteoglycans, and entactin/nidogen (see ¶ [029]). Chirila teaches the preparation further comprises TGF-beta, epidermal growth factor, insulin-like growth factor, fibroblast growth factor, tissue plasminogen activator, and/or other growth factors (see ¶ [030]). Chirila teaches wherein the preparation is Matrigel (see ¶ [007]-[013]). Chirila teaches the preparation is extracted from a tumor, such as the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (see ¶ [029]).
Regarding the limitations pertaining to the cell density, Chirila teaches culturing the skin fibroblast and imaging the fibroblast network changes. The images are taken at about 20 minutes to even about 72 hours or more after culturing (see ¶ [036]). Chirila teaches measuring the number of aggregates on a 10x image and an average number of 9 counting squares was used for cell counting with 50 cells/mm3 (e.g. 450 cells/10x) (see ¶ [039], [0104]-[0105], [0111]). Chirila teaches “after network degeneration (e.g., about 48 hours), cells migrate and reach confluence within a few days. This recovery is captured by a linear increase in fractal dimension. Recovery as measured by the slope and intercept of the fractal curves therefore shows quantifiable differences between AD, non-ADD, and AC cells” (see ¶ [049], [085]). Fig. 4 shows precision in the determination of average aggregate area per number of aggregates and Fig. 4B plots the area per number of aggregates as a function of initial cell density, showing an exponential relationship (solid lines) with a steeper rise for AD than for AC (i.e., the cell aggregation rate with respect to rate of change as compared to a non-Alzheimer’s disease standard) (see ¶ [009], [084]-[089]).
Examiner’s Response to Arguments
Applicant’s arguments filed on 04/17/2026 have been fully considered but they are not persuasive and deemed insufficient to overcome the prior art of record.
In response to Applicant’s reprised argument (addressing pages 2-3 of the remarks) that “Applicants maintain that Chirila fails to teach all elements of the claimed method. For example, the Examiner has not properly established how the cited paragraphs in the Chirila reference teach the skin-fibroblast cell densities of the claimed invention”: these arguments are not persuasive for the reasons maintained of record. In particular, the prior art of Chirila teaches the existence of large aggregates and the density of aggregates (number per unit area) which indicates that there is a plurality of densities per unit area. Chirila teaches “Fig. 4B plots the area per number of aggregates as a function of initial cell density” (see ¶ [009], [064], [078], [087]). It is noted that a text search of the instant specification does not reveal the words “plurality” or “densities” and further note that Chirila discloses that “The singular forms “a,” “an,” and “the” include plural reference unless the context dictates otherwise” (see Chirila at ¶ [015] and see the instant pre-grant specification at ¶ [0033]). Nevertheless, under the principles of inherency, since the prior art practices all the steps required by the claim, then the results should be the same (see MPEP 2112.02(I)). For example, it appears that both the claimed invention and prior art teaches similar culture conditions with a time period of from about 24 hours to about 48 hours (see Chirila at ¶ [007] and the instant pre-grant specification at ¶ [0050]). Accordingly, the prior art of Chirila remains applicable to the claims.
Conclusion
No claims were allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, this action is made final even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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