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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/2/2025 has been entered.
Claim Status
Currently, claims 39, 41-45, 61-63, and 87 are pending in the instant application. Claims 1-38, 40, 46-60, 64-86 have been canceled. No claims has been amended or added. This action is written in response to applicant’s correspondence submitted 12/2/2025. 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 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 Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims.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 Final.
Maintained Rejections
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 39, 41-45, 61-63, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (WO 2013/192616 A1, cited on IDS) in view of Mauerer (Experimental Dermatology, 2011, Vol 20, pp 502-507, cited on IDS). This rejection was previously presented and is reiterated below.
Wang teaches determining in a sample the expression level of at least two biomarkers including PRAME and immune genes NR4A1, and SOCS3 and at least one normalized biomarker in a sample obtained from a subject, generating expression values for each marker, using expression values in a regression to generate an output value and resulting output value is compared to cut off value derived from normalized expression values from samples in advance or benign melanocyte samples (calculating a combined score and classifying the sample as being a malignancy based on the combined score exceeding a reference value) (see pg. 2, lin2s 28-continued to page 3, line 12). Wang teaches changes in expression are normalized to at least one normalization marker (see pg. 19, lines 16-21, table 3) (claim 43-45). Wang teaches samples include skin biopsies (skin lesions) and sample containing melanoma suspect cells, FFPE tissue samples, and lymph nodes or internal organ for melanoma spread (see pg. 15, lines 13-34 and page 16, lines 1-10). Wang further teaches a first and second value of expression levels in samples that are benign and malignant (see pg. 15, lines 3-10 and pg. 17). Wang teaches differentially expressed genes in melanocyte containing samples including PRAME and immune genes NR4A1, and SOCS3. Wang further teaches, PRAME, NR4A1, and S100B analysis (see figure 10A). Wang teaches that one ordinarily skilled in the art will appreciate that the disclosure enables the identification of other combination of tables. Wang teaches expression of nucleic acid molecules can be detected by quantitative PCR or microarray analysis (see pg. 30 and pg. 38). Wang teaches data analysis of expression data and includes combining the measured expression of the at least two gene combination generating an output value for the sample and controls including benign and malignant melanoma and comparing the resulting output value to cut-off value that is either benign or malignant (See pg. 55) (combined score is recorded in a report) (claim 62-64). Wang teaches the combined scores of the expression of the biomarkers are used to generate a test value (using a linear model) (see pg. 54, lines 15-25) and teaches ROC analysis and logistic regression (see pg. 56 and 86)(claim 9-11). Wang teaches a classifier to classify samples into classes based on expression of genes in samples and information including diagnosis or scoring by cytologist or pathologists. (see pg. 52, lines 14-24) . Wang teaches during and after data input by a user (expression values) portions of the data processing is performed and can provide a score that is transmitted to the review’s computing environment to provide a result and generate a report in the reviewer’s computing environment (combined score is recording in a report communicated to the patients’ medical provider) (claim 62-64) (see pg. 58, lines 8-25) Wang teaches expression analysis methods are included for selecting a subject for treating melanoma or for selecting a subject for no treatment (classifying sample as low risk or high risk) (additional clinical parameter value communicated to the patients’ medical provider). Wang teaches administering a treatment regimen to a subject diagnosed as having primary melanoma. Wang teaches administering treatment including surgery to remove more tissue and treatment with a chemotherapeutic agent (see pg. 64, lines 6-18) and teaches chemotherapies include IL2, dacarbazine, and vemurafenib (see pg. 64, lines 29-33) (claim 87). Wang does not teach expression analysis and determining a combined score of the combination of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3. Wang does not teach S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 or housekeeping gene.
However it was well known in the art that S100A9 and CXCL9 are upregulated in melanoma. Mauerer teaches analysis of gene expression in melanoma. Mauerer teaches overlap of expression status of S100A9 and PRAME as previously reported genes associated with melanoma. Mauerer teaches analysis of gene expression by Affymetrix U133A 2.0 chip which comprises probes for S100A7, S100A8, S100A12, S100A10, S100A14, PI3, including CCL5, CD38, CXCL10, CXCL9, IRF1, LCP2, PTPN22, and PTPRC (claim 42) and housekeeping genes CLTC, MRFAP1, PPP2CA, PSMA1, RPL13A, RPL8, RPS29, SLCA3, and TXNL1 (claim 41). The claim only requires measuring the expression level of the gene and in the method of Mauerer each of the genes will be measured because the U133 2.0 chip comprises probes for each of the claimed genes.
Given the prior art teaches PRAME, S100A9, and CXCL9 status is associated with melanoma, it would have been prima facie obvious to the ordinary artisan at the time the invention was made to include analysis of additional genes using the U133 2.0 chip as taught by Maurer and include expression analysis of S100 related gene and immune genes, S100A7, S100A8, S100A12, S100A10, S100A14, PI3 and include additional housekeeping genes as taught by Mauerer in the method of Wang. The ordinary artisan would have been motivated to include expression analysis by U133 2.0 chip gene because the microarray comprises many probes that allows for measuring expression of many different genes including S100 related genes and immune genes S100A7, S100A8, S100A12, S100A10, S100A14, PI3, in the method of Wang because both Wang and Mauerer teach gene expression and association with melanoma including PRAME and Wang teaches that one of ordinary skill in the art would appreciate that the disclosure enables the identification of other combination of tables of genes, an ordinary artisan would have further concluded that using microarray hybridization and include a commercially available microarray, U133 2.0 as taught by Mauerer to measure expression of additional genes associated with melanoma and additional known housekeeping genes could be used included in the analysis of Wang. Additionally the skilled artisan would have a reasonable expectation of success that microarray hybridization for gene expression analysis can be tested in samples for melanoma because Wang teaches at least a two gene combination for melanoma detection and normalization of expression with housekeeping genes and Mauerer teaches genes associated with melanoma. Because both Wang and Mauerer et al teach gene status for identification of melanoma samples by normalization of gene expression data, it would have been obvious to one skilled in the art to include the microarray hybridization using a commercially available microarray, Affymetrix U133 2.0 as taught by Mauerer in the method of analysis and treatment of melanoma as taught by Wang in order to achieve the predictable result of determining gene expression normalized data and calculating a combined score of a gene panel and using housekeeping genes such as RSP29 or RPL4 based on a calculated score of the gene panel.
Response to Arguments
The response traverses the rejection on pages 6-9 of the remarks mailed 12/2/2025. The response is identical to the response mailed on 7/2/2025, which was previously considered. Applicant has not provided any new remarks. The following is the response previously provided. The response asserts that the combination of references fails to teach or suggest all claimed elements and there is no rationale or motivation to combine Wang and Mauerer. The response asserts that Wang and Mauerer alone or in combination do not teach or suggest measuring the expression level of a panel of genes in the sample from the patient wherein the panel of genes comprise PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14 and PI3. The response asserts that Mauerer does not teach combining the expression of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 together in a panel of genes and does not teach or suggest measuring the expression level of a panel of genes. This response has been reviewed but not found persuasive. The claims are not limited to only the panel of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 and the claims do not require or recite a panel of genes consisting of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3. The claims recite comprising measuring the expression of a panel of genes…wherein the panel of genes comprises. As such the claim encompasses additional genes beyond the genes recited in the claims. Mauerer teaches melanoma sample analysis using gene expression data by hybridization of Affymetrix U133 2.0 which comprises probes and analysis of gene expression of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3. Including the microarray U133 2.0 as taught by Maurerer in the method of Wang would have yielded the predictable result of determining gene expression of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3, normalizing the data, and calculating a combined score as taught by Maurer in the method of Wang because both Wang and Maurer teach gene expression analysis for melanoma diagnosis and treatment.
The response asserts that Mauerer merely provides an example of an investigator using an array gene chip having 22,000 probe sets representing 14500 human genes and does not teach the specific combination of the genes recited in claim 39. The response asserts there is no motivation to combine Wang and Maurer because Mauerer provides no teaching of the combination of genes in claim 39. This response has been reviewed but not found persuasive. As discussed above the claims are not limited to only the recited gene panel, the claims recite a method comprising determining expression of a gene panel comprising, as such the claims encompass more than the recited PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 gene expression. An ordinary artisan would have been motivated to use a commercially available microarray chip, as taught by Maurerer to identify and screen many different genes to identify additional genes associated with melanoma. Additionally the ordinary artisan would have been motivated to include analysis of additional genes because both Maurer and Wang teach gene expression analysis of identification of melanoma and treatment methods.
The response further asserts there is no reasonable expectation of success and the combination of Wang and Mauerer would not provide one of skill in the art with a reasonable expectation of success for carrying out the methods of claim 29. The response asserts that Wang does not teach analysis of S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 or housekeeping genes. The response asserts that Maurerer does not teach combining the expression of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 together in a panel. As addressed above, the claims are not limited to a panel of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3. The claims encompass a panel comprising PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 and teach measuring any level of expression. As such the ordinary artisan would have been motivated to use the Affymetrix array U133 2.0 in the method of Wang to allow for a more robust and comprehensive analysis of gene expressions levels in melanoma, including detecting differences in gene expression levels and comparing to housekeeping genes. When using the Affymetrix array U133 in the method of Wang, normalized and expression analysis comparison will include detecting and comparing expression levels of PRAME, S100A9, S100A7, S100A8, S100A12, S100A10, S100A14, and PI3 to detect a different in expression levels in melanoma patients.
For these reasons and reasons of record the rejection is maintained.
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).
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Claims 39, 41-45, and 61-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-17 of copending Application No. 18/493935 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 39 encompasses all that is recited in claims 1 of ‘935. Specifically the method of treatment comprising mRNA expression of PRAME, S100 related gene and immune gene, combining expression for a calculated score, classifying melanoma and administering treatment which is recited in instant claims 39, 41-47, 61-63 is encompassed by claims 2-12 of ‘935. Specifically claim 3 requires diagnosis by expression of a panel of genes which is encompassed by the limitations of claims 1 of ‘935.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 39, 41-45, and 61-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. US 11,834,719 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 39, 41-45, and 61-63 encompasses all that is recited in claim 1 of ‘719. Specifically the method of diagnosis comprising mRNA expression of PRAME, S100 related gene and immune gene in instant claims 1 is encompassed by claims 1 of ‘719. Additionally the dependent instant claims 41-45 and 63-65 encompass the calculations are recited in dependent claims 2-17 of ‘719. Specifically the housekeeping genes of claim 4 of ‘719 are encompassed by the housekeeping genes recited in instant claim 41. The combined score limitations of claims 43-45 of ‘719 is encompassed by the combined score recited in instant claims 10-11, 15-16 .
Claims 39, 41-45, and 61-63 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. US 11584967 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 39 encompasses all that is recited in claim 1 and 10 of ‘967. Specifically the method of diagnosing melanoma comprising mRNA expression of PRAME, S100 related gene and immune gene, combining expression for a calculated score, classifying melanoma is recited in instant claims 1 and 43-45 is encompassed by claims 1 and 10 of ‘967. Additionally the dependent instant claims 41-42 and 62-64 are recited in dependent claims 2-9 and 11-18 of ‘967.
Response to Arguments
The response addresses each of the double patenting rejections on page 10. The response acknowledges the rejection and elects to address this ground of rejection upon notification that the rejection has been made non-provisional all other conditions for patentability have been met and the instant claims are otherwise in condition for allowance. This response has been reviewed and because applicant did not point out supposed errors with the rejection, the rejection is maintained.
Conclusion
No claims are allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1634