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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/16/2026 has been entered.
Currently, claims 1, 5, 7-10, 12-13 are pending in the instant application. Claim 2-4, 6, 11, 14-19 have been canceled. This action is written in response to applicant’s correspondence submitted 03/16/2026. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims. 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 Non-Final.
Claims 1, 5, 7-10, 12-13 are under examination with regard to the elected combination of CCNB2, NEK2, RRM2, TOP2A, and CENPE.
Withdrawn Rejections
The rejection of claims 1, 5, 7-10, 12-13 under 35 USC 101 aare withdrawn in view of the amendment to the claims.
The rejection of claims 1, 5, 7-10, 12-13 under 35 USC 102 (a)(1) as anticipated by Gehrmann is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 5, 7-10, 12-13 under 35 USC 112(b) is iwhdrawn in view of the amendment to the claims.
New Grounds of Rejection
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 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.
Claims 1, 5, 7-10, 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Gehrmann (US 2009/0311700 A1) in view of Sgroi (US 2013/0281502 A1), Kung (Mol. Cancer Therapeutics, 2014, 13(8): 2104-15) , Sparano (Breast Cancer Res Treat 2012, 134:751-757) and Shubbar (BMC Cancer, 2013, 13:1, pp 1-10).
Gehrmann teaches prognosis of breast cancer patients based on measurement of expression level of marker genes in tumor samples of breast cancer patients (see para 1). Gehrmann teaches determining the expression level of at least one gene in a tumor sample, comparison of expression level with a predetermined threshold level, and determining prognosis which encompasses estimation of likelihood of metastasis free survival over a predetermined period of time, including 5 years (see 14-16 and 22). Gehrmann teaches marker genes include CCNB2, NEK2, RRM2, TOP2A, and CENPE (see table 1). Gehrmann teaches overexpression is determined when the expression level of the gene is at least 2 fold or higher than a reference cell type which include muscle cells or non-cancerous breast tissue cells (comparing the measured mRNA expression from tumor sample with mRNA expression level of same gene in healthy, non-tumor sample ) (see para 39) (claim 9). Gehrman teaches 5 marker genes are used (see para 50). Gehrman teaches obtaining node-negative breast cancer using tumor samples from breast cancer patients and expression was determined by Affymetrix HG-U133A array (see para 76 and 81) (hybridization using probe) (claims 5, 7-8) (node negative breast cancer, claim 13). Additionally the probes and genes recited in table 1 have sequences designated as SEQ ID NO 3 and SEQ ID NO 5-8, as the probes and the genes recited in table 1 encompass a sequence that encompasses each of the SEQ ID Nos for the elected gene combination (claim 10). Gehrmann further teaches ER positive breast cancer patient and ER negative breast cancer patient, thus including analysis of patients who are ESR1 positive or ESR1 negative (claim 12). Gehrmann teaches analysis of tumors that develop distant metastasis within five years versus those that are disease free by analysis of high or low expression (see para 92). Gehrmann teaches determining prognosis and 5 year survival based on high and low expression. Gehrmann teaches analysis of tumors that develop distant metastasis within five years versus those that are disease free by analysis of high or low expression (see para 92). Gehrmann does not teach assigning treatment with a chemotherapy to a patient that has a less than 70% likihood to relapse free survival. Gehrmann does not teach specific expression levels of NEK2, RRM2, TOP2A, CENPE, and CCNB2.
Sgori teaches gene expression levels are useful for providing prognostic determinations and predictive determinations, such as responsiveness to a course of treatment (see para 16). Sgori teaches gene expression levels of NEK2 and RRM2. Sgori further teaches gene expression analysis of five molecular grade genes which include NEK and RRM2 as well as ERBB2 and ESR, PGR (see para 99). Sgori teaches identification of subject for benefit from a switch in endocrine therapy (see para 21 and para 83). Sgori teaches determining prognosis of a patient by expression levels and then selecting a treatment for a patient within the gene expression (see para 78). Sgori teaches high risk (high expression) and low risk (low expression) (see para 81). Sgori teaches identifying patients for treatment and further teaches treating subjects with endocrine therapy (see para 20 and 21)
Kung teaches CENPE expression is elevated in breast cancer. Kung teaches increased expression of CENPE is strongly negatively correlated with disease specific survival (see pg. 2106, last paragraph).
Sparano et al. teaches TOP2A expression is detected in breast cancer. Sparano teaches TOP2 increased expression is significantly associated with recurrence and associated with significantly higher relapse rates at 5 years (see page 755, last column cont’d to page 756). Sparano teaches analysis of ESR1, PgR and ERBB2 and teaches ESR1 and PGR positive samples were analyzed (see pg. 752, 2nd paragraph) (claim 22). Sparano teaches analysis of increased TOP2A expression is useful for indicating the benefit of adding chemotherapy (see pg. 751, 1st column).
Shubbar teaches CCNB2 expression can stratify breast cancer patients in a high risk group and is a prognostic marker for unfavorable patient prognosis (see pg. 8, 2nd column). Shubbar teaches accuracy of patient prognosis may be improved by measuring CCNB2 expression in breast cancer (see pg. 8, 1st column). Shubbar teaches elevated expression of CCNB2 is associated with shorter disease specific survival (see figure 2). Shubbar further teaches mRNA expression of CCNB2 is consistent with protein expression level in breast cancer (see figure 5). Shubar teaches patients ER/PR status and HER2 status which includes a subset of patients that were ER/PR and HER2 positive (see table 1) (claim 22-23)
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the method of detecting expression of CCNB2, NEK2, RRM2, TOP2A, and CENPE and identifying prognosis of breast cancer as taught by Gehrmann to include further identifying treatment and administer treatment, including endocrine therapy or chemotherapy as taught by Sgori. The ordinary artisan would have been motivated to improve the method of identifying prognosis of breast cancer by expression of CCNB2, NEK2, RRM2, TOP2A, and CENPE, to stratify patients using a 5 gene set because Gehrman suggests a 5 gene analysis and Sgori uses 5 genes to identify prognosis of breast cancer patient. Because Sgori teaches expression of NEK2 and RRM2, Kung teaches increased expression of CENPE, Shubbar teaches increased expression of CCNB2, and Sparano teaches increased expression of TOP2A in breast cancer with high risk breast cancer subjects, it would have been obvious to further determine the median expression of the five genes with the predictable result of increased expression being associated with high risk breast cancer and likelihood of distant metastasis as the art teaches each of the genes are increased in breast cancer and associated with poorer outcomes. The ordinary artisan would have been motivated to determine the median expression level of CENPE, TOP2A, CCNB2, NEK2, and RRM2 and have a reasonable expectation of success that increased median expression of the genes would be associated with high risk and distant metastasis free 5 year survival to stratify patients as taught by Gehrman, Sgori,, Sparanoa, Kung, and Shubbar. Additionally the ordinary artisan would have been motivated to improve the method of Gehrman and further include assigning treatment, including endocrine therapy for patients with patient has distant metastasis free 5 year suvival and further treat patients with likelihood of distant metastasis free 5 year survival with endocrine therapy because both Sgori and Gehrmann teach gene expression analysis in breast cancer patients along with disease free survival in breast cancer patients. Additionally the ordinary artisan would have been motivated to include chemotherapy treatment in patients with increased expression of CENPE, TOP2A, CCNB2, NEK2, and RRM2 because Sparano teaches chemotherapy treatment in patients with increased risk of recurrence and Sgori, Sparano, Kung, and Shubbar teach increased expression of CENPE, TOP2A, CCNB2, NEK2, and RRM2 and risk of distant metastasis and it was known in the art to treat breast cancer patients with risk of recurrence with chemotherapy. The ordinary artisan would have had a reasonable expectation of success that the use of assigning treatment after gene expression analysis and identifying patients with disease free survival as taught by Sgori and include analysis of patients that were ESR1, PGR and ERBB2 positive as taught by Shubbar and was routine in the art to determine for breast cancer diagnosis could be used with the method of Gehrmann. Furthermore the ordinary artisan would have had a reasonable expectation of success of treating subjects with increased expression of CENPE, TOP2A, CCNB2, NEK2, and RRM2 with chemotherapy as the art demonstrates that of CENPE, TOP2A, CCNB2, NEK2, and RRM2 is increased in high risk recurrent breast cancer and the art teaches administering chemotherapy to patients with high risk recurrent breast cancer and administering endocrine therapy to low risk or patients with low expression.
Because both Gehrmann and Sgori teach gene expression analysis for stratifying patients for disease free survival and prognosis of breast cancer and Sgori, Sparano, Kung, and Shubbar teach expression of CENPE, TOP2A, CCNB2, NEK2, and RRM2 in breast cancer patients and stratifying patients as 5 year recurrence rate, it would have been obvious to one skilled in the art to include the additional step of assigning treatment, specifically endocrine therapy for patients that have likelihood of distant metastasis free 5 year survival as taught by Sgori or chemotherapy for patients have likelihood of distant metastasis as taught by Sparano in the method of Gehrmann, in order to achieve the predictable result of determining median expression level, stratifying patients and assigning and treating breast cancer patients with a hormone therapy to patients that have a likelihood of relapse free 5 year survival of over 70% or with chemotherapy in patients that are less likely to have a relapse free 5 year survival.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 7-10, 12-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11649504B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims require a method of assigning treatment to a breast cancer patient based on likihood of patients distant metastasisi free 5 year survival whereas the claims of ‘504 require a method of assigning treatment to a breast cancer patient based on the likihood of the patient’s relapse free 5 year survival. Both claims require measuring the same gene set, stratifying the patients into groups based on high and low expression levels, assigning the same treatment based on the 5 year survival and carrying out the same treatment. While the instant claims encompass likihood of patients distant metastasisi free 5 year survival this encompasses relapse, as such the claim scope is not patentably distinct from meahc other. While applicants assert in the remarks filed on 3/16/2026, that the claims of ‘504 are directed to distinct methods from which is currently claimed, this traversal is not found persuasive because distant metastasis free 5 year surivial is encompassed by relapse free 5 year survival and both claims require expression analysis of the same gene set. While instant claim 1 recites median mRNA expression of each gene and claim 1 of ‘504 is median mRNA of each gene set, the gene set can encompass median mRNA expression of each gene. The claims do not recite specifically mRNA expression of each individual gene, both claims require median mRNA expression of each gene, the recitation of gene set does not distinguish a different method step. As such the claims are not patentably distinct.
Conclusion
No claims are allowable.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1634
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