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 .
Application Status
This action is written in response to applicant’s correspondence received 2/12/2026. Claims 8 and 10-12 are cancelled. Claims 2-7, 9, and 13-15 are pending. Claims 2-4 and 13 are amended. Claims 2-7, 9, and 13-15 are examined herein.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Objections - withdrawn
Objection to claim 8 for minor informalities is withdrawn in view of Applicant’s cancellation of claim 8.
Claim Rejections - 35 USC § 112 - withdrawn
Rejection of claims 2-9 and 13-15 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards the invention is withdrawn in view of Applicant’s amendment to clarify in claim 2 that “the expression level” in part iv) is GILZ and not a different protein, in claims 3 and 4 to add “further”, and correcting issues of insufficient antecedent basis.
Claim Rejections - 35 USC § 103 - maintained
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.
Claims 2-7, 9 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Haim et al. (Resistance of LPS-activated bone marrow derived macrophages to apoptosis mediated dexamethasone. SCIENTIFIC REPORTS; published 3/10/2014; cited in the IDS filed 6/7/2021), in view of Mammen et al. (Cytomorphometric neutrophil and monocyte markers may strengthen the diagnosis of sepsis. Journal of intensive care medicine; published 12/13/2016). This rejection has been amended to reflect Applicant’s amendment to cancel claim 8.
Regarding claim 2, Haim teaches a mouse model for sepsis is LPS-induced septic shock (p. 2, left column, paras 1 and 2). Haim teaches that dexamethasone corticosteroid treatment enhanced viability in murine RAW 264.7 macrophages and blood monocyte-derived macrophages (p. 2, left column, para 3) and further teaches the importance of determining whether a patient suffering from clinical states such as sepsis is eligible for treatment with a corticosteroid (p. 2, left column, para 1 through right column, para 1). Haim teaches that tissue specific macrophages are derived from circulating monocytes which originate from bone marrow progenitors (p. 1, para 1). Haim teaches step i) purifying macrophages derived from bone marrow from mice (p. 9, Methods – Generation of BMDM). Haim teaches step ii) culturing macrophages in vitro in the presence and absence of dexamethasone (Figures 3 and 7). Haim teaches step iii) determining the expression level of glucocorticoid-induced leucine zipper (GILZ) in the presence and absence of dexamethasone (p. 6, left column, para 1 through right column, para 2; Figure 7) and that measuring a ratio between the GILZ expression in macrophages with dexamethasone treatment to macrophages without the dexamethasone at 1μM led to a 10-fold increase, which is greater than 1 (p. 6, left column, para 1 through right column, para 2; Figure 7). Haim further teaches that glucocorticoids improve the clinical outcome of septic shock (p. 2, left column, paras 1 and 2) and teaches dexamethasone treatment at different concentrations in vitro (Figure 4), suggesting a need to arrive at a therapeutically effective amount of the glucocorticoid.
However, Haim does not specifically teach that the macrophages and/or monocytes are isolated from a blood sample from a patient suffering from sepsis.
Mammen’s disclosure is directed to improvements in diagnosing sepsis with cytomorphometric neutrophil and monocyte biomarkers (see entire document).
Regarding claim 2, Mammen teaches the need for better sepsis diagnosis (p. 1, Introduction). Mammen teaches collecting blood samples from patients suffering from sepsis as well as nonseptic ICU controls and healthy blood donors (p. 2 – Patients and Methods). Mammen further teaches measuring monocyte volume, content (conductivity), and granularity (scatter; VCS) parameters (p. 2 – Patients and Methods).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Haim’s methods determining whether glucocorticoids should be used in treating sepsis, including culturing macrophages in vitro in the presence and absence of a corticosteroid, determining the GILZ expression level after corticosteroid treatment is higher than without treatment, and treating a sepsis patient with a corticosteroid with Mammen’s method of measuring monocytes in blood collected from sepsis patients to arrive at the claimed invention. Haim teaches the importance of determining whether a patient suffering from clinical states such as sepsis is eligible for treatment with a corticosteroid (p. 2, left column, para 1 through right column, para 1). One would have been motivated to do so because Haim teaches elevated GILZ expression in macrophages with dexamethasone treatment (p. 6, left column, para 1 through right column, para 2; Figure 7), that tissue specific macrophages are derived from circulating monocytes (p. 1, para 1), and that glucocorticoids improve the clinical outcome of septic shock (p. 2, left column, paras 1 and 2) and Mammen teaches that monocyte characteristics to improve sepsis diagnosis (entire document). One would have had a reasonable expectation of success because Haim and Mammen are directed to improvements in the diagnosis and treatment of patients suffering from sepsis. Thus, the claimed invention as a whole is prima facie obvious.
Regarding claim 3, Mammen teaches patients suffering from systemic inflammatory response syndrome (p. 2, right column, para 1).
Regarding claim 4, Mammen teaches patients suffering from acute respiratory distress syndrome (Table 2).
Regarding claim 5, Haim teaches cortisol and cortisone (p. 1, para 1).
Regarding claim 6, Haim teaches the corticosteroid is dexamethasone (entire document).
Regarding claim 7, Mammen teaches blood monocytes (entire document).
Regarding claim 9, Haim teaches measuring the expression level of GILZ with PCR (p. 9, Methods; Figure 7).
Regarding claims 13 and 14, Mammen further teaches administering therapeutically effective antibiotic therapy promptly after sepsis diagnosis along with other supportive treatment, without a need to further categorize the sepsis as corticosteroid responsive or non-responsive. Mammen teaches this non-corticosteroid treatment for a sepsis patient as a preliminary treatment, therefore it would have been obvious for one of ordinary skill in the art to have administered the antibiotic therapy when the GILZ biomarker expression level is not greater than 1 (indicating that the sepsis is not eligible for treatment with a corticosteroid) (p. 1 - Introduction).
Regarding claim 15, Haim teaches culturing the macrophages in vitro for 6 hours after dexamethasone treatment, which is within the claimed time frame of 30 minutes to 18 hours (p. 9, Methods – ELISA; Figures 3 and 7).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed 2/12/2026 have been fully considered but they are not persuasive. Applicant argues that because Haim teaches that dexamethasone, a corticosteroid, increases the expression of GILZ in macrophages (Figure 7), one of ordinary skill in the art would recognize that administration of a corticosteroid will induce the expression of GILZ in a septic patient. Applicant further argues that “Haim does not teach that such induced expression will not occur in patients for whom corticosteroid therapy is not effective” and thus it would not be obvious to provide a method for determining responsiveness to corticosteroid treatment as set forth in claim 2. Applicant further argues that claim 13 requires two alternative treatments depending on the expression level GILZ: either administration of a corticosteroid when the ratio is greater than 1 or administration of a non-corticosteroid sepsis therapy when the ratio is not greater than 1 and that Haim does not teach or suggest such a treatment decision based on the expression level of GILZ. Applicant argues that Mammen does not compensate for the deficiencies of Haim as Mammen was only relied upon for teaching isolating monocytes from blood of septic patients.
Applicant’s arguments are not persuasive because Haim teaches the importance of determining whether a patient suffering from clinical states such as sepsis is eligible for treatment with a corticosteroid (p. 2, left column, para 1 through right column, para 1) and it would have been obvious to one of ordinary skill in the art to have modified Haim’s methods with the monocytes of Mammen (as explained in the 103 rejection above) to provide a method for determining responsiveness to corticosteroid treatment to improve sepsis diagnosis. Independent claims 2 and 13 are not limited to non-responsiveness to corticosteroids (measured by increased GILZ expression). Thus, it is not required that Haim teach that such induced expression will not occur in patients for whom corticosteroid therapy is not effective. Claim 14 limits the therapies to non-corticosteroid sepsis therapies, so claim 14 is limited to non-responsiveness to corticosteroids. Therefore, the rejection of record in maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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