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 .
Response to Amendment
Applicant’s response filed 29 December 2025 has been received and entered. Claim 1 has been amended and claims 2-9, 13 and 15 have been canceled. Claims 1, 10-12 and 14 are currently pending in the instant application.
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 objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant’s response and withdrawn.
Applicant’s arguments filed 29 December 2025 have been fully considered but are not found to be persuasive.
Response to Arguments
Applicant’s arguments directed to the previous grounds of rejection made under 112(a), 112(b) and 112(d) have been obviated by the amendment to the claims to correct the noted deficiencies. However, as noted in the previous Office action, the previous rejections made under 35 USC § 103 may be reinstated if the claims are amended to remove the limitations which were considered to be new matter. In view of the removal of the new matter, the following rejections are applicable to the currently amended claims.
Claim Interpretation
Claim 1 has been amended to recite that severe sepsis is “sepsis associated with organ dysfunction, hypoperfusion abnormality, or sepsis-induced hypotension” and that septic shock is “severe sepsis with sepsis-induced hypotension persisting despite adequate fluid resuscitation, along with the presence of hypoperfusion abnormalities or organ dysfunction”.
Toker et al. (Eurasian J. Med. 53(1): 40-47, 2021) clearly state that the Third International Consensus Definitions for Sepsis and Septic Shock in 2016 defined sepsis as life-threatening organ dysfunction that develops as a result of an impaired host response to infection (see second paragraph on page 40) as well as defining severe sepsis as the presence of symptoms of organ disorder, hypoperfusion or hypotension with sepsis (see page 41, top of column 2).
Based on the definitions in the prior art (Toker has a publication date of 2021 but is citing definitions from 2016 consensus), a prior art statement of “sepsis” is equivalent to the claim’s definition for “severe sepsis”, which is stated to be “sepsis associated with organ dysfunction”.
Additionally, Toker et al. make clear that a score of 2 or more points on the SOFA is required for the diagnosis of sepsis (page 41, column 2, under heading of “Sepsis-3 (2016)”). Therefore, a patient has sepsis would have been known to meet the limitation of having a SOFA score of 2 or more.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1 and 10-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Thermo Scientific (cited by Applicant) in view of Joannidis, M. (Sem. In Dialysis 22(2): 160-164, 2009) and Ricci et al. (cited by Applicant).
Thermo Scientific discloses several methods which use proadrenomedullin (proADM) or midregion proadrenomedullin (MR-proADM) as a biomarker for disease in subjects who are critically ill. The title of the publication is “rapid risk assessment and early warning of developing complications in critically ill infectious patients”. At page 6 of the reference, the level of adrenomedullin (which is a fragment of proADM) was measured in critically ill subjects (septic patients) and increasing levels of ADM were found to be predictive of development to severe sepsis or septic shock. At page 7 of the reference, the level of MR-proADM was measured in blood samples from septic patients (critically ill) to predict organ failure and the need for treatment. Thermo Scientific at page 7 states that MR-proADM was “measured from the same blood sample drawn immediately on admission”, meeting the limitation that the sample is obtained upon admission to the ICU. MR-proADM levels which were above 2.2 nmol/L were used as a cutoff for predicting severe illness. At page 9 of the reference, the level of PCT (procalcitonin) was measured in addition to MR-proADM wherein levels of PCT and MR-proADM were indicative of severe disease and the need for more intensive treatment. At page 13 of the reference, levels of MR-proADM were measured in blood samples. High levels of MR-proADM (above 2 nmol/L) were predictive of pneumonia related complications. It was concluded that MR-proADM values of less than 0.5 nmol/L correlated with patients who did not suffer from any adverse complications while patients with levels above 2 nmol/L were identified as being at risk of developing complications. Adverse outcomes included respiratory failure, shock, acute renal failure and ICU admission. It was concluded that patients who show increased levels of ADM may benefit from an earlier transfer to the ICU in order to initiate a higher treatment intensity. Thermo Scientific does not identify the treatment/therapy to be administered to the patients.
While Thermo Scientific does not specifically recite a SOFA score of the patients, the patients were diagnosed as being septic. However, a score of 2 or more points on the SOFA is required for the diagnosis of sepsis, therefore, this limitation is met by the patients of Thermo Scientific (see Toker et al. (Eurasian J. Med. 53(1): 40-47, 2021) at (page 41, column 2, under heading of “Sepsis-3 (2016)”).
Joannidis teaches that renal replacement therapy is commonly used as a therapy for critically ill subjects with sepsis and septic shock. Joannidis teaches that renal replacement therapy is also beneficial as an immunomodulatory tool helping to influence the systemic consequences of severe sepsis and septic shock (see page 160, column 2, 1st paragraph).
Ricci et al. teach that renal replacement therapy in critically ill patients with acute kidney injury is common routine practice (see abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Thermo Scientific to assess the risk of critically ill infections patients of developing complications by measuring the level of adrenomedullin in said patients, wherein increasing levels of ADM are predictive of development to severe sepsis or septic shock and cause to initiate earlier transfer to the ICU in order to initiate a higher treatment intensity. It additionally would have been obvious to administer renal replacement therapy as the higher treatment intensity as suggested by Thermo Scientific because Joannidis teaches that renal replacement therapy is also beneficial as an immunomodulatory tool helping to influence the systemic consequences of severe sepsis and septic shock. Additionally, Ricci et al. teach that renal replacement therapy in critically ill patients with acute kidney injury is common routine practice (see abstract) and Thermo Scientific teaches that ADM is predictive for determining critically ill patients and organ failure and the need for treatment. One of ordinary skill in the art would have a reasonable expectation of success in combining the method of Thermo Scientific with the treatment modality of Joannidis because Thermo Scientific teaches that elevated ADM levels (above 2 nmol/L) were predictive of developing complications and Jannidis teaches that renal replacement therapy is beneficial for treating severe sepsis and septic shock. One would have had a reasonable expectation of success because Ricci et al. teach that renal replacement therapy is common routine therapy for patients with organ failure in the ICU.
Claim(s) 1 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Thermo Scientific (cited by Applicant) in view of Joannidis, M. (Sem. In Dialysis 22(2): 160-164, 2009) and Ricci et al. (cited by Applicant) and further in view of Espana et al. (cited by Applicant).
The teachings of Thermo Scientific, Joannidis and Ricci et al. are as provided above. The combination of references do not teach an immunoassay as described in claim 14.
Espana et al. teach that the level of proADM in blood samples from patients with community-acquired pneumonia were found to be predictive for those patients who had more severe disease and required admission to the hospital (see abstract). Espana et al. also measured PCT as a biomarker (see abstract). Espana et al. used the biomarkers (PCT and proADM) to select patients eligible for outpatient care as well as for selecting patients in need of any type of intensified monitoring or treatment (see page 458, column 1, paragraph 3). A level of proADM above 2.0 nmol/L was defined as high risk (see page 461, column 2, lines 3-4) and proADM was measured using a sandwich style immunoassay (see page 459, column 1, paragraph 3) which meets the limitations of the assay recited in claim 14. While Espana et al. does not specify specific treatment strategies, proADM levels were used to classify patients as being in need of specific treatment strategies (see page 464, column 1, paragraph 2). As seen in Table 5, patients in Risk class 3 include 39 patients in acute renal failure. Espana et al. does not teach treatment of the high risk patients with renal replacement therapy.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Thermo Scientific to assess the risk of critically ill infections patients of developing complications by measuring the level of adrenomedullin in said patients, wherein increasing levels of ADM are predictive of development to severe sepsis or septic shock and cause to initiate earlier transfer to the ICU in order to initiate a higher treatment intensity. It also would have been obvious to use the assay method described in Espana et al. to measure ADM/proADM because Espana et al. teaches that it is successful for measuring ADM/proADM levels in subjects who are critically ill. It additionally would have been obvious to administer renal replacement therapy as the higher treatment intensity as suggested by Thermo Scientific because Joannidis teaches that renal replacement therapy is also beneficial as an immunomodulatory tool helping to influence the systemic consequences of severe sepsis and septic shock. Additionally, Ricci et al. teach that renal replacement therapy in critically ill patients with acute kidney injury is common routine practice (see abstract) and Thermo Scientific teaches that ADM is predictive for determining critically ill patients and organ failure and the need for treatment. One of ordinary skill in the art would have a reasonable expectation of success in combining the method of Thermo Scientific using the assay method of Espana et al. with the treatment modality of Joannidis because Thermo Scientific teaches that elevated ADM levels (above 2 nmol/L) were predictive of developing complications and Jannidis teaches that renal replacement therapy is beneficial for treating severe sepsis and septic shock. One would have had a reasonable expectation of success because Ricci et al. teach that renal replacement therapy is common routine therapy for patients with organ failure in the ICU.
Conclusion
No claim is allowed.
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 Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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