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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/23/2026 has been entered.
Status of the Claims
Claims 1, 2, 6-8, and 12-14 are currently pending.
Claims 1, 6, 7, and 12 are amended.
Claims 12-14 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 3-5 and 9-11 remain cancelled.
Claims 1-2 and 6-8 have been considered on the merits.
Withdrawn Rejection
The objections made onto claim 1 are withdrawn in light of the amendments submitted on 02/23/2026.
New and Maintained Rejections Necessitated by Amendment
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.
Claim(s) 1, 2, and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Zabirnyk et al (Vascular Pharmacology 122–123 (2019) 106583) (reference of record), Bowler et al (Am J Physiol Heart Circ Physiol 315: H1614–H1626, 2018)(reference of record).
Regarding claim 1, Zabirnyk teaches cell culture-based valve calcification assay by employing valve interstitial cells (VIC), isolated from patients with and without signs of valve calcification, to a novel calcification treatment compound, SNF472, and evaluating its inhibition of calcification as required by claims 1, 7 and 8 (Abstract, lines 1-4). The assay is completed by separating VICs into osteogenic media, basic growth media, and variable treatment concentration groups with SNF472 as required by claim 2 (pg. 2, column 2, lines 20-24). Calcification is seen in the osteogenic media group due to “applying osteogenic media to the at least one valve interstitial cell to promote differentiation and calcification” as required by claims 1, 6 and 7 (Fig. 4A). This addresses the limitation of exhibiting at least one pathological process causing aortic and mitral valve calcification as required by claims 6 and 7 because the instant claim 7 teaches that this process is induced in the same manner as the art (i.e. inducing through osteogenic media application), therefore the art teaches the at least one pathological process causing valve calcification. Zabirnyk teaches staining using Alizarin Red to assess the calcification as required by claim 1 and 7 (pg. 2, column 2, para 4). Further, Zabirnyk teaches the quantification, which meets the limitation of detecting a presence or absence of at least one calcific cellular nodule, of the stain spectrophotometrically, which meets the limitation of being performed by computer-assisted morphometric analysis software of a digital image as required by claims 1 and 7. Zabirnyk also teaches that the stained cells are photographed in a photomicrograph as required by clam 1 (Fig. 1). Zabirnyk teaches that a “SNF472 blocked calcification even when calcification was ongoing. However, the present study showed that the effect was more pronounced the earlier the agent was given, suggesting it is important to initiate treatment with SNF472 as early as possible in order to inhibit or limit the calcification process (pg. 4, column 1, lines 21-22).
Zabirnyk does not explicitly teach that the quantification of the photomicrograph is expressed as an area of the stain binding divided by a total area shown by the photomicrograph as required by claim 1. However, Zabirnyk presents Fig. 2A which plots the relative calcification as a percent, and states “Calcification was measured by Alizarin red staining and quantified spectrophotometrically. (A) Relative calcification, values are dot plots + mean.” (Fig. 2). This data demonstrates expressing the area of the stain binding divided by a total area shown in the photomicrograph and subsequently represented as a percent calcification as required by claim 1.
Zabirnyk does not teach that the cells used are a stable cell line obtained from an adult Ts(H2-K1-tsA58) mouse, also known as the Immortomouse as defined by the specification, as required by claim 1.
However, Bowler teaches a similar embodiment to that of Zabirnyk where calcification of VICs is evaluated from Immortomice. Bowler teaches that VICs are isolated from 8 week old adult Immortomice as required by claim 1 (pg. 2, col. 2, para 1-2). Bowler also teaches that the immortalized cell line can theoretically be expanded indefinitely however they chose to limit passage number to 30 which meets the limitation of a “stable cell line” as required by claim 1 and 7 (pg. 2, Col. 2, para 1-2). The limitation of a “stable cell line” is further met by Fig. 1B which demonstrates three separate adult Immortomouse-derived VIC cell lines which each stably express one of the following genotypes: WT CDH11, a heterozygous knockout of CDH11, and a homozygous knockout of CDH11as required by claim 1 (Fig. 1B). Additionally, Bowler teaches the use of Alizarin red stained slides in which the calcification fractions were calculated as the ratio of positive calcification pixel to the total number of valve leaflet pixels, which meets the limitations of claim 1 because the pixels of Bowler are a measurement of area of the photomicrograph.
One of ordinary skill in the art would find it obvious to combine the cell-culture based calcification assay taught by Zabirnyk with the VICs isolated from Immortomice taught by Bowler. The motivation to combine would be that Bowler teaches “[w]ith the number of calcific aortic stenosis patients expected to double by 2050, and possibly triple by 2060 (12, 40), there is a need for a better understanding of the biological mechanisms driving CAVD to develop
well-tolerated, noninvasive pharmacological therapies for valvular calcification” (pg. 1, column 2, lines 10-15). One of ordinary skill in the art would have a reasonable expectation of success because Bowler teaches the comprehensive method of isolating the VICs from the Immortomice for use in calcification assays.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 02/23/2026 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 6) that Zabirnyk and Bowler do not teach the newly added limitations requiring that the cell provided is a stable cell line of at least one VIC and that it is derived from an adult mouse.
In response, this argument is not found persuasive. Bowler teaches a stable cell line of VIC that is derived from an adult mouse. Bowler teaches that VICs are isolated from 8 week old adult Immortomice as required by claim 1 (pg. 2, col. 2, para 1-2). Bowler also teaches that the immortalized cell line can theoretically be expanded indefinitely however they chose to limit passage number to 30 which meets the limitation of a “stable cell line” as required by claim 1 and 7 (pg. 2, Col. 2, para 1-2). The limitation of a “stable cell line” is further met by Fig. 1B which demonstrates three separate adult Immortomouse-derived VIC cell lines which each stably express one of the following genotypes: WT CDH11, a heterozygous knockout of CDH11, and a homozygous knockout of CDH11as required by claim 1 (Fig. 1B).
Therefore, the argument is not found persuasive.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/DAVID A MONTANARI/Examiner, Art Unit 1632