DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
The claim set and Applicant’s remarks filed May 19, 2026 have been entered.
Claim 6 is canceled.
Claims 1-4 and 14 are withdrawn from further consideration as being drawn to nonelected inventions.
Thus, claims 5 and 7-13 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on December 19, 2025:
(I) The objection to claims 5 and 7-8 are withdrawn in view of Applicant’s amendments to these claims.
(II) The rejection of claim 11 under 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment to this claim.
(III) The rejection of claim 6 under pre-AIA 35 U.S.C. 103(a) is withdrawn in view of Applicant canceling this claim.
Response to Arguments
The Examiner has reviewed and considered Applicant’s arguments regarding the current 103 rejections of record. However, the Examiner maintains these rejections as discussed below.
Applicant argues:
(A) Claim 5 now expressly requires that step (b) is performed by detecting a portion of MCM subunits located in the nucleus as compared with a portion located in the cytoplasm, wherein said invention is to detect the localization and formation of the MCM complex, which reflects the functionality of the MCM complex and is totally different from the detection of gene expression (mRNA and/or protein) levels in the prior arts, see Applicant’s remarks, pg. 9, last paragraph – pg. 10, first paragraph.
(B) The claimed invention uses nuclear/cytoplasmic localization of MCM subunits as a functional readout of human MCM-complex inhibition, see Applicant’s remarks, pg. 11, last paragraph.
(C) Iwami’s screening method concerns the quantitative changes in the gene expression level (mRNA or protein amount), not in the disruption of the functional human MCM complex, not the interference with interactions between MCM subunits, and not in the comparison of nuclear versus cytoplasmic localization as a readout of functional MCM-complex formation, see Applicant’s remarks, pg. 12, first paragraph.
(D) Iwami does not disclose or suggest that the portion of MCM subunits in the nucleus versus the cytoplasm can be used to assess whether a candidate compound disrupts formation or functionality of the MCM complex, see Applicant’s arguments, pg. 12, second paragraph.
(E) It appears the Examiner relies on Iwami’s alteration of MCM2-MCM7 levels, together with Ishimi’s disclosure that MCM proteins are essential for DNA replication as allegedly satisfying or suggesting disruption of a functional MCM complex; however, because Ishimi teaches that MCM proteins are essential for DNA replication, increased MCM protein levels would be directionally consist with promoting replicative activity, not disrupting complex formation, see Applicant’s remarks, pg. 12, last paragraph – pg. 13, first paragraph.
(F) The cited art provides no teaching or suggestion that a person of ordinary skill would compare nuclear and cytoplasmic portions of MCM subunits to screen for anticancer compounds that disrupt formation of the functional human MCM complex, see Applicant’s remarks, pg. 13, last paragraph.
(G) Iwami’s method operates by detecting whether a test substance changes the gene expression level (mRNA or protein amount) of MCM2-MCM7 in cancer cells, and comparing that expression/protein amount against a control; and therefore, amended claim 5 does not operate by identifying compounds based on altered MCM gene expression (mRNA or total MCM protein amount), see Applicant’s remarks, pg. 21, second paragraph.
With respect to Applicant’s arguments (A), (D), (F) and (G), the Examiner notes Ishimi-1 has been incorporated to teach the assessment of localization of the Mcm subunits within the nucleus as compared to the cytoplasm.
With respect to Applications arguments (B)-(C) and (E), the Examiner notes Iwami teaches the substance selected in this way changes the protein amount of Mcm2 to 7 in cancer cells, and it has an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells which is discussed in greater detail below.
(H) The claimed invention also provides unexpected technical effects where the anticancer compounds identified by the claimed method exhibit anticancer activity while causing significantly less damage to normal cells compared with conventional cytotoxic compounds, and wherein Applicant exemplifies said agent as 17β-deacetyltanghinin, see Applicant’s remarks, pg. 14, first paragraph.
With respect to Applicant’s argument (H), the Examiner notes the cited references include the Cheenpracha reference which teaches compound 3, identified as 17β-deacetyltanghinin as discussed below.
(I) The Examiner’s proposed four-reference combination reflects impermissible hindsight because it uses Applicants’ disclosure as a roadmap to select and retrofit disparate teachings that were not linked in the art in the manner now claimed, see Applicant’s remarks, pg. 18, last paragraph.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Accordingly, the Examiner notes the cited references of Iwami, Cheenpracha, Ishimi-1 and Ishimi-2 teach each and every limitation required within the instant claims which was within the level of ordinary skill in the art at the time the claimed invention was made as discussed in greater detail below.
(J) Cheenpracha does not identify compound 3 as 17β-deacetyltanghinin, and nevertheless supplies that identification by relying on Applicants’ disclosure – stating that the Cheenpracha compound “has the same structure as the elected species, as evidenced by” Applicants’ Fig. 1, see Applicant’s remarks, pg. 19, last paragraph.
With respect to Applicant’s argument (J), the Examiner notes that Applicant’s disclosure is only relied upon to show that Cheenpracha’s compound 3 is in fact the compound known as 17β-deacetyltanghinin. Additionally, the Examiner further notes Cheenpracha teaches compound 3 as an anticancer agent as discussed below.
(K) Ishimi-2 does not teach that a compound should be screened by determining whether it blocks interactions among MCM subunits and thereby prevents nuclear localization of the functional human MCM complex, see Applicant’s remark’s, pg. 20, first paragraph.
With respect to Applicant’s argument (K), the Examiner notes Ishimi-2 is not relied on for a method of screening compounds it is the Iwami reference; and as such said compounds of Iwami are taught to change the protein amount of Mcm2 to 7 in cancer cells by having an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells as discussed below.
(L) Reconstructing Iwami to operate in this manner would replace Iwami’s expression (mRNA/protein amount) based screen with an entirely different functionality/localization screen and would require changing the assay target, the assay readout, and the technical basis for identifying hit compounds, see Application remarks, pg. 22, first full paragraph.
With respect to Applicant’s argument (L), the Examiner notes the addition of Ishimi-1 above which teaches the comparison of Mcm2-7 protein levels in the nucleus as compared to the cytoplasm does not change the operation of Iwami as argued by Applicant above; as the Examiner notes within the modified 103 rejections below both Iwami and Ishimi are both drawn to detecting the amount of Mcm2-7 proteins in both total cell extract and chromatin-bound fractions in cancer cells, specifically HeLa cells as discussed in greater detail below.
Thus, Applicant’s arguments (A)-(L) have been fully considered but are not found persuasive.
New Claim Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on May 19, 2026, where the limitations in pending claims 5 and 7-13 as amended now have been changed.
Therefore, rejections from the previous Office Action, dated December 19, 2025, have been modified and are listed below.
35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
(I) Claims 5 and 7-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Iwami et al. (Published 30 April 2004, JP-2004131435-A, English Machine Translation, PTO-892 mailed 12/19/2025) in view of Cheenpracha et. al. (Published August 2004, Chemical and Pharmaceutical Bulletin, Vol. 52, No. 8, pp. 1023-1025, PTO-892 mailed 12/19/2025), Ishimi et al. (hereafter referred to as "Ishimi-1", Published 24 February 2003, European Journal of Biochemistry, Vol. 270, Issue 6, pp. 1089-1101, PTO-892) and Ishimi et al. (hereafter referred to as "Ishimi-2", Published 03 April 1998, Journal of Biological Chemistry, Vol. 273, Issue 14, pp. 8369-8375, PTO-892 mailed 12/19/2025).
Regarding claims 5 and 7-11, Iwami provides an anticancer agent which exerts an action specific to cancer cells without changing non-cancer cells, see pg. 1, abstract, objective.
Iwami teaches a method for screening (e.g. the method of screening, required in claim 5, line 1) a substance having the ability to specifically change the protein amount of Mcm2 to Mcm7 in cancer cells (e.g. the population of cells, required in claim 5, line 3), for example an anticancer agent containing the substance as an active ingredient (e.g. the anticancer compound, required in claim 5, line 1), see pg. 2, paragraph [0001].
Iwami teaches Mcm proteins exist as six types of proteins from Mcm2 to Mcm7 and all members are proteins known to play an essential role in genome replication, see paragraph [0004].
Iwami teaches for example cultured cancer cells derived from human cancer tissues are preferably used (e.g. the MCM subunits required in claim 9), see pg. 4, paragraph [0014], paragraph 2.
Iwami teaches the test substance is added to a cancer cell and a non-cancer cell (e.g. contacting a candidate compound with a population of cells, required in claim 5, line 2) and the protein amount of Mcm2 to Mcm7 in these cells is detected (e.g. determining an amount, required in claim 5, line 2), see pg. 3, paragraph [0010].
Iwami teaches the protein content of non-cancer cells is detected and the protein content of Mcm2-7 is not changed, and only the protein content of Mcm2-7 of cancer cells is changed, see pg. 4, lines 2-3.
Iwami teaches “change” means to decrease or increase the protein amount of Mcm2 to Mcm7, but the protein amount of Mcm2 to 7 in the cancer cells to which the test substance is added is increased, see pg. 5, paragraph [0023].
The Examiner reasonably interprets based on the teaching of Iwami in the preceding paragraph said teaching illustrates that the test substance of Iwami is added to cancer cells in which the protein amount of Mcm2 to 7 is increased.
Iwami teaches the substance selected in this way changes the protein amount of Mcm2 to 7 in cancer cells, and it has an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells, see pg. 5, paragraph [0024].
Iwami teaches test substances added to these cells include for example plant extracts, and wherein the compound may be a known compound, see pg. 4, paragraph [0017].
Iwami teaches the detection and quantification of the protein content of Mcm2 to Mcm7 in tissue cells can be arbitrarily selected and used from commonly used methods known per se, for example a coloring method or an immunohistological staining method where the measurement can be performed using a fluorescent antibody method, wherein as a fluorescent substance used for labeling an antibody, a method for labeling a secondary antibody can be used (e.g. the indirect fluorescence process (immunostaining), required in claim 7), see pg. 7, paragraph [0036].
Iwami teaches when the immunostaining of individual cells was compared, stronger immunoreactivity was observed in large nuclei in cancer cells than in cells in the basal layer of normal squamous epithelium, and the expression level of MCM protein per cell increased, see pg. 10, paragraph [0061].
Iwami teaches it was found in HeLa cells used as cancer cells where the expression of all proteins of Mcm 2 to 7 was increased as compared to WI-38 cells used as normal cells, this was confirmed not only in total extract but also in the chromatin fraction extract (e.g. MCM proteins bound to chromatin, required in claim 10), see pg. 9, paragraph [0056].
Iwami teaches since the Mcm protein has functions as DNA helicase and ATPase screening can be performed using these activities as indices (e.g. the enzymatic functions, required in claim 11), see pg. 5, paragraph [0025].
With respect to the limitations:
(i) “a period of time” when referring to contacting the candidate compound with a population of cells, required in claim 5, lines 2-3; the Examiner reasonably interprets this limitation as a physical limitation well within the scope of the artisan as Iwami already teaches screening test compounds as anticancer agents comprising a test substance as an active ingredient by adding said compound into cancer cells, for example the HeLa cells of Iwami as discussed above. Thus, physical limitation (i) will be met by the method of Iwami above.
(ii) “anticancer compounds with inhibitory effects on the human MCM complex”, required in claim 5, lines 1-2; and (iii) “a functional human MCM complex formed from its subunits, wherein said anticancer compound exhibits inhibitory effects by disrupting the formation of the functional human MCM complex by interfering with interactions between MCM subunits” when determining the amount of said MCM complex after contact of the candidate compound with the population of cells recited in claim 5, lines 2-3, as required claim 5, lines 3-10; the Examiner reasonably interprets these limitations as physical or functional limitations that are met by the method of Iwami above, as Iwami teaches the detection and quantification of the protein content of Mcm2 to Mcm7 in tissue cells, specifically cancer cells where the protein amount of Mcm2 to 7 is increased, e.g. the HeLa cells of Iwami; and the test substance is added to said cancer cells where the protein amount of Mcm2 to Mcm7 in these cells is detected; and whereby said substance specifically changes the protein amount of Mcm2 to Mcm7 in cancer cells by adding said test substance to said cancer cells which has an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells; and as Iwami further explains Mcm2 to Mcm7 all play an essential role in genome replication.
Therefore, limitations (ii) and (iii) are reasonably interpreted by the Examiner to be physical/functional consequences of contacting the anticancer compound with said population of cells.
Additionally, as evidenced by Ishimi-2, Ishimi-2 discloses minichromosome maintenance (MCM) proteins play an essential role in eukaryotic DNA replication; where biochemical analyses have indicated that MCM2–7 proteins interact; and in extracts of mitotic human cells, a complex of approximately 600 kDa, containing all six MCM proteins, have been identified; wherein based on the molecular mass of each MCM protein, this complex is probably a hexamer containing a single molecule of the six MCM proteins, see pg. 8369, left column, paragraph 1.
Thus, the Examiner reasonably interprets when the substance of Iwami has an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells; the substance of Iwami disrupts the formation of the MCM complex; in view of Ishimi-2 disclosing MCM proteins are essential in DNA replication and form a hexamer complex comprising MCM2-7 proteins, and Iwami teaching said substance has an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells. Accordingly, the Examiner reasonably interprets the limitation of “disrupting the formation of the functional human MCM complex by interfering with interactions between MCM subunits” is met by the method of Iwami as discussed above.
Although, Iwami does not teach (a) the anticancer compound, required in claim 5, line 1, is the elected species 17-β-deacetyltanghinin; (b) wherein step (b) is performed by detecting a portion of MCM subunits located in the nucleus as compared within a portion located within the cytoplasm, required in claim 5, lines 4-6; and (c) the direct fluorescence process, required in claim 8.
However, in the same filed of endeavor of screening for an anti-cancer compound, with respect to limitation (a), Cheenpracha teaches that deacetyltanghinin (compound 3), from Cerebera manghas, has cytotoxic activity, suggesting its use in the treatment of cancer, see pg. 1023, abstract and pg. 1025, Table 2.
The Examiner respectfully notes Cheenpracha does not identify compound 3 as 17-β-deacetyltanghinin, however, the Examiner further respectfully notes the compound depicted as compound 3 within the Cheenpracha reference has the same structure as the elected species, as evidenced by compound 4 in Figure 1 of the instant disclosure which identifies compound 4 within Figure 1 of the instant disclosure as 17beta-Deacetyltanghinin (DAT).
Therefore, the Examiner reasonably interprets compound 3 of Cheenpracha is 17-β-deacetyltanghinin.
It would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have incorporated the 17-β-deacetyltanghinin of Cheenpracha as a test substance within the screening method as taught by Iwami above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to have added the 17-β-deacetyltanghinin of Cheenpracha within the screening method of Iwami in order to test whether or not 17-β-deacetyltanghinin is a substance having the ability to specifically change the protein amount of Mcm2 to Mcm7 in cancer cells by having an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells as taught by Iwami above.
One of ordinary skill in the art would have had a reasonable expectation of success of having added the 17-β-deacetyltanghinin of Cheenpracha as a test substance within the screening method as taught by Iwami above; as Cheenpracha teaches compound 3, identified as 17-β-deacetyltanghinin, has cytotoxic activity against a variety of cancer cell lines as discussed in Table 2 of Cheenpracha above; additionally Iwami teaches the test substance may be from plant extracts and may be a known compound as discussed above.
With respect to limitation (b), in the same filed of endeavor of expression of Mcm proteins in cancer cells, Ishimi-1 teaches comparing the level of expression of Mcm proteins among human HeLa cells and normal human fibroblasts (WI-38); where an increase of proteins examined were detected in HeLa cells at 6-10 times the level found in WI-38 cells on average, and this increase was observed both in total cellular proteins and in the chromatin-bound fraction, see pg. 1089, abstract, left column.
Ishimi-1 teaches Mcm proteins within the total cell extracts and the chromatin-bound fraction were analyzed by immunoblotting using anti-Mcm, see pg. 1093, Fig. 1.
Ishimi-1 teaches quantification and comparison of Mcm amounts of Mcm2-7 from data in Fig. 1, in HeLa cells with respect to the two fractions, the total cellular protein and chromatin-bound protein, see pg. 1092, Table 1.
Ishimi-1 teaches approximately one-third of total Mcm protein was found to be recovered in the chromatin-bound fraction in HeLa cells, and thus a considerable portion of Mcm protein is present in the nucleoplasm and/or easily released from chromatin; and that titration of said chromatin-bound fraction showed there was 6-13 times more Mcm2-7-chromatin-bound proteins in HeLa cells than in WI-38 cells, see pg. 1094, right column, results, paragraph 1.
The Examiner reasonably interprets the teachings of Ishimi-1 above, specifically the comparison of Mcm2-7 protein levels of the total cell extract against the chromatin-bound fraction in cancer cells, exemplified as HeLa cells, corresponds to the recitation of “by detecting a portion of MCM subunits located in the nucleus as compared within a portion located within the cytoplasm” recited in claim 5.
It would have been obvious been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have incorporated the teachings of Ishimi-1 above into the method of Iwami above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results, as both Iwami and Ishimi-1 are both drawn to detecting the amount of Mcm2-7 proteins in both total cell extract and chromatin-bound fractions in cancer cells, specifically HeLa cells as discussed above.
One of ordinary skill in the art would have been motivated to incorporate the teachings of Ishimi-1 above into the method of Iwami above in order to detect and quantify whether the substance of Iwami changes the protein amount of Mcm2 to 7 in cancer cells by having an effect of acting on abnormalities in mechanisms such as DNA replication in cancer cells as taught by Iwami above.
One of ordinary skill in the art would have had a reasonably expectation of success to have incorporated the teachings of Ishimi-1 into the method of Iwami, because both Iwami and Ishimi-1 are drawn to detecting the amount of Mcm2-7 proteins in both total cell extract and chromatin-bound fractions in cancer cells, specifically HeLa cells.
With respect to limitation (c) and within the same field of endeavor of fluorescence processes, Ishimi-2 teaches native forms and truncated forms of the mouse MCM2 gene were cloned in pEGFP-N1 (e.g. the plasmid, required in claim 8, line 1) at the HindIII sites to synthesize MCM2-GFP fusion proteins where the carboxyl-terminal ends of the MCM2 proteins were fused to the amino-terminal end of GFP (green fluorescent protein) (e.g. the one or more MCM subunits fused with a fluorescent protein, required in claim 8, line 3); where the cloned DNAs were transfected into HeLa cells using Tfx 20 (Promega) (e.g. the direct fluorescence process, required in claim 8), see pg. 8370, left column, paragraph 2.
The Examiner respectfully notes with particular respect the limitation “the location of said fluorescently labeled MCM subunits is then detected after said cells have been treated with said candidate compound for a certain duration”, required in claim 8, lines 3-5; the Examiner reasonably interprets this limitation as a physical limitation as Iwami teaches when the immunostaining of individual cells was compared, stronger immunoreactivity was observed in large nuclei in cancer cells than in cells in the basal layer of normal squamous epithelium; and Ishimi-1 teaches comparison of the amount of Mcm2-7 proteins in both total cell extract and chromatin-bound fractions in cancer cells, specifically HeLa cells; which the Examiner notes is the cell line used by Iwami and Ishimi-2 above. Thus, the Examiner reasonably interprets the physical limitation discussed above is met by the method of Iwami.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated limitations (a)-(c) within the screening method as taught by Iwami above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to have added the 17-β-deacetyltanghinin of Cheenpracha within the screening method of Iwami in order to test whether or not 17-β-deacetyltanghinin is a substance having the ability to specifically change the protein amount of Mcm2 to Mcm7 in cancer cells by having an effect of acting on abnormalities in mechanisms such as DNA replication in said cancer cells as taught by Iwami above and (c) to use the fluorescence method of Ishimi-2 as an immunohistological staining method where the measurement can be performed using a fluorescent substance as taught by Iwami as discussed above.
One of ordinary skill in the art would have had a reasonable expectation of success of incorporating limitations (a)-(c) within the screening method as taught by Iwami above; as Cheenpracha teaches compound 3, identified as 17-β-deacetyltanghinin, has cytotoxic activity against a variety of cancer cell lines as discussed in Table 2 of Cheenpracha above; additionally Iwami teaches the test substance may be from plant extracts and may be a known compound as discussed above; and Iwami further teaches the detection and quantification of the protein content of Mcm2 to Mcm7 in tissue cells can be arbitrarily selected and used from commonly used methods known per se, for example a coloring method or an immunohistological staining method as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claims 12-13 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Iwami et al. (Published 30 April 2004, JP-2004131435-A, English Machine Translation, PTO-892 mailed 12/19/2025), Cheenpracha et. al. (Published August 2004, Chemical and Pharmaceutical Bulletin, Vol. 52, No. 8, pp. 1023-1025, PTO-892 mailed 12/19/2025), Ishimi et al. (hereafter referred to as "Ishimi-1", Published 24 February 2003, European Journal of Biochemistry, Vol. 270, Issue 6, pp. 1089-1101, PTO-892) and Ishimi et al. (hereafter referred to as "Ishimi-2", Published 03 April 1998, Journal of Biological Chemistry, Vol. 273, Issue 14, pp. 8369-8375, PTO-892 mailed 12/19/2025) as applied to claims 5 and 7-11 above, and further in view of Lau et al. (Published 26 July 2010, Oncogene, Vol. 29, pp. 5475-5489, PTO-892 mailed 12/19/2025).
Iwami, Cheenpracha, Ishimi-1 and Ishimi-2 address claims 5 and 7-11 as written above. Although, Iwami, Cheenpracha, Ishimi-1 and Ishimi-2 do not teach the conformation step performed using flow cytometry, required in claims 12-13.
However, in the same filed of endeavor of detecting and quantifying Mcm proteins, Lau exemplifies small interfering RNA (siRNA) knockdown of MCM2, MCM3 and MCM7 inhibited medulloblastoma (MB), where flow cytometry data indicated that knockdowns of MCM2 or MCM7 in DAOY cells further increased the arrests and eventually induced prominent apoptosis after 48 h, see pg. 5479, right column, paragraph 1. Lau teaches flow cytometric histograms of propidium iodide-stained MB cells, treated with transfection reagents alone or with MCM2 siRNA, MCM3 siRNA or MCM7 siRNA, pp. 5483-5484, Figure 4b.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated flow cytometry as taught by Lau into the detection and quantification of the protein content of Mcm2 to Mcm7 in tissue cells as taught by Iwami above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to incorporate the flow cytometry of Lau into the method of Iwami above in order to detect and quantify the amount of Mcm2 or Mcm7 protein in the total cell extract and in the chromatin-bound fractions within the cancer cells of Iwami after screening the test compound as taught by Iwami above.
One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated the flow cytometry of Lau into the method of Iwami above, as Iwami teaches the detection and quantification of the protein content of Mcm2 to Mcm7 in tissue cells can be arbitrarily selected and used from commonly used methods known per se, for example as a coloring method; and wherein Lau teaches flow cytometry was conducted using propidium iodide as a fluorescent dye as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
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 JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
Prosecution Insights