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 .
Claims 1, 3-7, 9-15, 17, 18, 24, 27, 28, 43 and 49 are pending. Claims 1, 3-7, 9-10, 43 and 49 are withdrawn. Claims 11-15, 17, 18, 24, 27 and 28 are currently under examination.
This office action is in response to the amendment filed on 12/3/2025.
All previous rejection not reiterated in this office action are withdrawn.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 11-15, 17-20, 24 and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (IDS).
Yang teaches a study that examined cytokines in plasma samples from 53 COVID-19 cases, divided into severe cases (34) and moderate cases (17) (lines 60-65). Yang teaches that IP10, MCP3 and IL-1ra were independent predictors for the progression of COVID-19 (lines 21-29). Yang teaches serial detection of IP10, MCP3 and IL-1ra in 14 severe cases showed continuous high levels of these cytokines were associated with disease deterioration and fatal outcome, making them biomarkers that closely associated with disease severity and outcome of COVID-19 (lines 19-32). Yang teaches both groups received antiviral treatment (lines 66-67). Yang teaches notably, IP10 in the severe cases possessed a high and similar expression level at all groups of sample collection time, whereas IP10 in moderate cases was significantly lower and further decreased a lot at >=15 d.a.o. (lines 92-97). Yang teaches the viral load showed obvious correlation with IP10 (lines 99-100). Yang teaches not only pathogen but also pathogen induced cytokine storm should be considered during the treatment, and therapy strategy with a combination of antimicrobial and immunotherapy may produce a more favorable outcome (131-134). Yang teaches IP10 plays a crucial role in the pathogenesis of SARS-CoV-2, and exacerbation of the pathology of ARD, and modulators such as antibody targeting IP10 may be a promising therapeutic strategy in the treatment of acute phase of ARDS to ameliorates acute lung injury (lines 139-146).
The teaching from Yang teaches measuring IP10 in a sample of subject (Figure 2 and lines 351-355), said subject already received antiviral treatment (lines 66-67). However, Yang does not specifically teach changing the treatment when the level of IP10 is above a predetermined threshold.
It would have been obvious to an ordinary skilled in the art to conclude from the study of Yang that IP10 plays a crucial role in the pathogenesis of SARS-CoV-2, wherein high level is associated with severe cases. The ordinary skilled in the art would recognize the previous antiviral treatment alone may not be effective when the level of IP10 is high, and altering treatment to include additional agents that lowers IP10 level would have been an obvious choice as suggested by Yang (lines 144-146). Therefore, the claimed invention of claim 11-14 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 15, Yang teaches IP10 plays a crucial role in the pathogenesis of SARS-CoV-2, and exacerbation of the pathology of ARD, and modulators such as antibody targeting IP10 may be a promising therapeutic strategy in the treatment of acute phase of ARDS to ameliorates acute lung injury (lines 139-146).
Regarding claims 17 and 18, Figure S1 shows measuring expression of IP10 at different time points, whereas the initial IP10 level is above about 103 pg/ml in all severe cases at 0-7 d.a.o (bottom graph). As such, IP10 level above 1000 pg/ml may serve as a predetermined threshold level for altering treatment.
Regarding claim 24, Yang teaches remeasuring IP10 as shown in Figure S1.
Regarding claim 27, Yang teaches patients receiving antiviral treatment and corticosteroid (line 134).
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang, in view of Sun et al (Experimental and Therapeutic Medicine, 2019, Vol. 18, pages 4637-4644). This is a new ground of rejection necessitated by amendment.
Sun et al. teaches testing different dose and time course of corticosteroid treatment with acute respiratory distress (ARDS) syndrome (title). Sun et al. teaches that the use of low dose corticosteroid significantly reduced the mortality rate of patients with ARDS, and the duration of mechanical ventilation and significantly improved PaO2/FiO2 ratio (abstract, and page 4642, 1st col).
It would have been obvious to an ordinary skilled in the art to conclude from the study of Yang that IP10 plays a crucial role in the pathogenesis of SARS-CoV-2, wherein high level is associated with severe cases for reason discussed above. The ordinary skilled in the art would recognize the previous antiviral treatment alone may not be effective when the level of IP10 is high, and altering treatment to include additional agents would yield favorable outcome because Yang teaches “therapy strategy with a combination of antimicrobial and immunotherapy may produce a more favorable outcome.” Yang also teach that corticosteroids can downregulate proinflammatory cytokine transcription and subsequently inhibit the cytokine storm. Although high dose of corticosteroids may be a concern when treating H7N9, the ordinary skilled in the art would be motivated to use low dose corticosteroids because Sun et al. teaches doses and time course of corticosteroids makes a big difference in treating ARD, which may result from SARS-CoV-2 infection. Therefore, the claimed invention of claim 28 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Response to Arguments
Applicant argues that Yang teaches a therapeutic strategy wherein IP10 is directly targeted with an anti-IP-10 antibody in order to neutralize its pro-inflammatory effects during acute viral infection, which makes IP10 a pathogenic effector molecule, whose reduction is presumed to confer therapeutic benefit. Applicant argues that the present claims recites a different clinical paradigm that monitors IP10 levels and altering treatment based on whether IP10 level crosses a defined threshold, wherein IP10 is not a therapeutic target, but a biomarker signal used to guide treatment decisions. Applicant argues that the claimed invention applies regardless of whether the subject is showing symptoms of severe or non-severe infection. Applicant argues that Yang teaches against using a corticosteroid as a second line treatment in response to elevated IP10 because Yang teaches using anti-IP10 antibody.
The above argument has been fully considered but deemed unpersuasive. The teaching of Yang is not limited to identifying IP10 as an effector molecules, because Yang teaches “we report biomarkers that closely associated with disease severity and outcome of COVID-19.” (page 2, line 31-32), and “these results indicated that these three cytokines could be considered as biomarkers to predict disease progression and outcome of SARS-CoV-2 infections.” (line 126-128). It would have been obvious to an ordinary skilled in the art that IP10 may be used as a biomarker for monitoring treatment course(s). As discussed in the above rejection, while Yang indicates high dose corticosteroid is not beneficial for treating certain viral infection such as H7N9, Sun et al. teach low dose corticosteroid reduces mortality rate of patients with ARDS, and the duration of mechanical ventilation and significantly improved PaO2/FiO2 ratio (abstract, and page 4642, 1st col). As such, for patients being treated with antiviral agent as the first treatment, it would have been obvious to an ordinary skilled in the art that patients with high level of IP10 would benefit from treatment with low dose of corticosteroid to reduce mortality.
Conclusion
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 CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637