CTFR 17/570,315 CTFR 74930 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 07-42-07 AIA A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 5/21/2026 has been entered. 12-151 AIA 26-51 12-51 Status of Claims Currently, claims 43, and 46-48 are pending in the instant application. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are reiterated and constitute the complete set being presently applied to the instant Application. Response to applicants arguments follow. This action is FINAL. 07-103 AIA The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims. Claim Rejections - 35 USC § 103 07-21-aia AIA Claim s 43 and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Ramilo (Ramilo et al; Blood, vol 109, pages 2066-2077; 2007) in view of Melchjorsen (Melchjorsen et al; Journal of Interferon and Cytokine Research; vol 29, NO: 4; pages 1-10; 2009) and further in view of Levin (Levin et al; US 2015/0011415; 1/8/2015) . With regard to claim 43, Ramilo teaches gene expression analysis in PBMCs (claim 46) in patients with different types of acute infections for the purpose of identifying genes whose expression patterns discriminate between different types of infections, including between bacterial vs viral infections, as well as different types of bacterial infections (see abstract). Ramilo teaches blood samples were collected (page 2066, col 2) from patients with E. coli , S aureus , S pneumoniae , Influenza A and healthy controls (claim 47). Ramilo teaches gene expression analysis was carried out using microarrays (claim 48), including Affymetrix GeneChips and Illumina BeadChips (page 2067, col 1), as well as confirmation with real time PCR (page 2075, col 1). Ramilo teaches that RNA was isolated using the RNeasy kit. Ramilo teaches different gene signatures which were able to differentiate between Influenza A and bacterial infections (table 4), including OAS1. Ramilo also teaches gene signatures that were able to discriminate between E. coli and S. aureus , including JUP (table 5). Ramilo teaches that the gene signatures can be used for hospitalized patients to distinguish and diagnose particular infectious diseases. Ramilo teaches patients with bacterial infections were treated with antibiotics while patients with viral infections were treated with antiviral agents (see table 2). Ramilo does not teach analysis of OASL, however Melchjorsen teaches that analysis of expression of OAS1 and OASL in response to viral infection revealed that the expression of OASL is rapidly increased in response to viral infection (see abstract) to a greater extent than OAS1 (see for example figure 2). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, to include analysis of OASL expression as taught by Melchjorsen in the method of Ramilo, for the purpose of providing a more thorough list of genes whose expression levels can identify and diagnose bacterial vs viral infections. Given that Ramilo teaches expression of OAS1 and JUP can be used to distinguish and diagnose bacterial vs viral infection, and Melchjorsen teaches that OASL expression was also increased in response to viral infection, the ordinary artisan would have expected that the analysis of the gene expression of a combination of genes, including OASL and JUP would be capable of diagnosing viral vs bacterial infections with a reasonable expectation of success. Ramilo and Melchjorsen do not teach determining the patient has a bacterial or viral infection using a score calculated from the gene expression levels of the biomarkers, however Levin teaches processing gene expression data for diagnosis of infection (see para 0005). Levin teaches (para 0006-0009) normalizing or scaling numeric values of the gene expression data, designating numeric values to be negative or positive, optionally refining the discriminatory power of the up regulated and down regulated genes by statistically weighting numeric values, summating the positive and negative numeric values to provide a composite score and comparing that score to a control score for comparison so that the sample can be designated as positive or negative for relevant infection. Levin teaches that this allows for simple diagnostic tests which are suitable for use in clinical settings (see para 0004). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have constructed a gene expression diagnostic score as taught by Levin, in the method of gene expression diagnostics for bacterial and viral infection taught by Ramilo and Melchjorsen because Levin teaches it allows for simple diagnostic tests which are suitable for use in clinical settings. It would have further been prima facie obvious to the ordinary artisan to administer antibiotics to patients determined to suffer from bacterial infections based on the gene expression levels and to administer antiviral agents to patients determined to suffer from viral infections, as taught by Ramilo, based on gene expression levels for the obvious benefit of providing treatment to the infected patients. Response to Arguments The response traverses the rejection and asserts that Melchjorsen’s data is gathered from virally infected cells in vitro and that the office action does not establish that the same gene expression responses would be expected in whole organisms. This argument has been thoroughly reviewed but was not found persuasive because Ramilo teaches that a gene signature comprising a number of genes, including OAS1 and JUP, can be used to differentiate between viral and bacterial infections. Melchjorsen’s analysis which revealed that OAS1 was induced by viral infection would therefore be expected. The behavior of the additional genes, including OASL, in Melchjorsen’s analysis would therefor appear informative of viral infection as well. Melchjorsen specifically states “the behavior of the OASL gene is consistent with the behavior of an antiviral gene” (see abstract). The response’s arguments that just because OASL is induced by virus infection does not mean it can discriminate between viral and bacterial infection is not found persuasive because the claims are not limited to discrimination based solely on the expression levels of JUP and OASL. As evidenced by Ramilo, a gene signature of a number of different genes was found to discriminate between bacterial and viral infection. Therefore, the addition of OASL to the gene panel of Ramilo would provide a reasonable expectation of success that the expression levels of OASL could be used similarly to OAS1, that is to indicate the presence of viral infection. It is also noted that the arguments set forth in the response regarding the ability of OASL to discriminate between viral and bacterial infection are attorney arguments and cannot take the place of evidence on the record. As set forth in the MPEP 716.01(c) and also brought to applicants attention in previous office actions, the arguments of counsel cannot take the place of evidence in the record. In re Schulze , 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.” It is noted, however, that applicant should be aware of the timeliness of submitting evidence (see MPEP 716.01 (A)). Accordingly, the rejection is maintained. Conclusion No claims are allowed. 07-42-09 AIA 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 examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone. 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, Winston Shen, can be reached on (571) 272-3157. The fax phone number for 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. /JEHANNE S SITTON/Primary Examiner, Art Unit 1682 Application/Control Number: 17/570,315 Page 2 Art Unit: 1682 Application/Control Number: 17/570,315 Page 4 Art Unit: 1682 Application/Control Number: 17/570,315 Page 5 Art Unit: 1682 Application/Control Number: 17/570,315 Page 6 Art Unit: 1682 Application/Control Number: 17/570,315 Page 7 Art Unit: 1682 Application/Control Number: 17/570,315 Page 8 Art Unit: 1682
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