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 .
Applicant's response to the previous Office action, dated November 21, 2025, has been received. By way of this submission, Applicant has amended claims 1-2, 4, 12, 21, 81, 94, 95, and 99, cancelled claim 5, and introduced new claims 100-103.
Claims 1-4, 6-14, 16-17, 21, 80-81, and 92-103 are pending in the application. Claims 21, 80, and 96 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed September 11, 2024.
Claims 1-4, 6-14, 16-17, 81, 92-95 and 97-103 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated August 27, 2025.
Claim Objections
Claim 2 was previously objected to due to minor grammatical informalities.
Applicant's amendments to the claims have addressed this issue, and this objection is hereby withdrawn.
Response to Amendment
Applicant argues that the references to Spencer (US20170009297A1), Angeletti (Clin Chem Lab Med. 2013 May;51(5):1059-67), Anderberg (US20150177260A1), and Eyged (Biomark Gene, 2017, 1(1):1-8) do not teach every aspect of the claims as amended; specifically, the references do not teach that the adverse event is a cardiovascular or cerebrovascular event and a postsurgical infection that occurs within 30 days of the surgery and is related to the surgery itself or the postsurgical course. Applicant further argues that the cited references do not teach that the claimed treatment method for a single patient that suffers both of a postsurgical infection and a cardiovascular or cerebrovascular event, wherein proADM is measured within one day before or three days after surgery and wherein the treatment of the patient is based upon said determined level.
Applicant's arguments in view of the amendments to the claims are persuasive for this combination of references only, and the rejection under 35 U.S.C. 103 over Spencer in view of Angeletti, Anderberg (US20150177260A1), and Eyged is withdrawn.
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-4, 6-14, 16-17, 81, 92-95 and 97-99 are rejected under 35 U.S.C. 103 as being unpatentable over Spencer (US20170009297A1) in view of Angeletti (Clin Chem Lab Med. 2013 May;51(5):1059-67), Anderberg (US20150177260A1), Eyged (Biomark Gene, 2017, 1(1):1-8), and Lundberg (Crit Care. 2016 Jun 9;20(1):178). This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
Spencer teaches methods for analyzing a biological sample to predict and monitor the development of sepsis utilizing a biomarker (para. 0001). Spencer further teaches that this method may be useful in identifying patients likely to develop sepsis, to monitor patients with sepsis, and potentially inform patient treatment (para. 0029). As sepsis is a blood infection, Spencer teaches this aspect of claims 2-4 and 6-10.
Spencer further teaches that samples may be taken from patients who were undergoing abdominal surgery, and that patients undergoing abdominal surgery are at risk of developing sepsis (para. 0060), which is pertinent to claim 81.
Spencer further teaches that biomarker levels may be compared to a threshold value (para. 0088).
Spencer further teaches that samples may be taken multiple times 1 to 7 days before and 1 to 7 days after surgery (para. 0061), which is pertinent to claims 11-13.
Spencer further teaches that monitoring biomarker levels is useful to predict and monitor the development of sepsis (para. 0039), which is pertinent to claim 17.
Spencer further teaches that the surgery may be abdominal surgery (para. 0060) and elective surgery (para. 0062), which is pertinent to new claims 97-98.
However, Spencer does not teach proADM as a biomarker for sepsis and a postsurgical cardiovascular or cerebrovascular event.
Angeletti teaches that levels of mid-regional pro-adrenomedullin (MR-proADM) at certain cut-off values (i.e. a threshold value) is useful in the early diagnosis of sepsis (i.e., bacterial infection in the blood), which is pertinent to claims 2-4 and 14.
Angeletti further teaches testing levels of proADM in samples from patients (page 1060, right column).
Angeletti further teaches that adrenomedullin is a prognostic biomarker in patients with heart failure (page 1065, right column, first paragraph). According to Applicant’s definition of “cardiovascular event”, and “myocardial injury” at page 60, heart failure is both a cardiovascular event and myocardial injury, which is pertinent to claims 6-10.
Anderberg teaches that evaluation of biomarkers is useful for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in sepsis patients (para. 0008).
Anderberg further teaches the use of threshold values of biomarkers to assess patient outcomes (para. 0015), and the use of diagnostic thresholds may be used to estimates of the consequences of treatment (para. 0072-0073).
Anderberg further teaches that a change in the level of a sepsis biomarker may be used to assess risk of sepsis (para. 0020).
Anderberg further teaches that once a diagnosis is obtained, the clinician can readily select a treatment regimen that is compatible with the diagnosis, such as intravenous antibiotics (para. 0080-0088), which is pertinent to claims 16 and 94.
Eyged teaches that patients with postoperative complications, such as infections, have significantly higher levels of MR-proADM levels in comparison to patients without complications, when MR-proADM levels are measured one or three days after surgery (page 4, second paragraph and Figure 3, also see page 5, right column, first paragraph: "In predicting postoperative sepsis MR-proADM was earlier elevated compared to PCT and CRP.").
Eyged further teaches that the patient may be undergoing elective abdominal surgery (Abstract: Methods), and that patients undergoing major abdominal surgery have increased postoperative plasma adrenomedullin levels (page 6, right column, third paragraph), which is pertinent to claim 98.
Eyged further teaches a cutoff point of 1.2 nmol/L for MR-proADM at either one day or three days after surgery (page 5, left column, second paragraph), which is pertinent to claim 99.
Lundberg teaches that MR-proADM is associated with myocardial injury in patients with sepsis (page 5, right column, second paragraph: "In this exploratory study we demonstrated significant relationships between MR-proADM/CT-proET-1 and myocardial injury. ... This finding supports a biologically plausible relationship as both pro-hormones are strongly vasoactive and may play key roles in sepsis associated myocardial injury.").
Lundberg also teaches that increased MR-proADM is associated with poor cardiovascular outcomes, and ADM is upregulated in patients with sepsis (page 5, right column, third paragraph).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Spencer, Angeletti, Anderberg, Eyged, and Lundberg to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since Spencer, Angeletti, Anderberg, Eyged, and Lundberg are all concerned with biomarkers for sepsis. Spencer teaches that sepsis is a known concern in patients with abdominal surgery, and sepsis can be predicted by the assessment of biomarkers in patient samples. Angeletti, Eyged, and Lundberg all teach that proADM is one such biomarker that correlates with early detection of sepsis, and Anderberg teaches suitable treatment methods once a biomarker for sepsis has been detected. Additionally, Lundberg teaches a relationship between increased levels of MR-proADM and myocardial injury in patients with sepsis. The ordinary artisan, following the teachings of Lundberg, would be aware that sepsis patients with increased levels of MR-proADM are also at increased risk of myocardial injury, with patients undergoing abdominal surgery being a relevant population, according to Spencer. One of ordinary skill in the art could apply the proADM biomarker of Angeletti, Eyged, and Lundberg and the treatment method of Anderberg to the diagnostic methods of Spencer by known methods, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
Claims 100-103 are rejected under 35 U.S.C. 103 as being unpatentable over Spencer (US20170009297A1) in view of Angeletti (Clin Chem Lab Med. 2013 May;51(5):1059-67), Anderberg (US20150177260A1), Eyged (Biomark Gene, 2017, 1(1):1-8), and Lundberg (Crit Care. 2016 Jun 9;20(1):178) as applied to claim 1 above, and further in view of Reddy (World J Cardiol. 2015 May 26;7(5):243–276). This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
The teachings of Spencer, Angeletti, Anderberg, Eyged, and Lundberg have been discussed supra. However, none of Spencer, Angeletti, Anderberg, Eyged, and Lundberg teach an anti-ischemic agent, clopidogrel, an anticoagulation therapy, or a stent implantation.
Reddy teaches the use of clopidogrel and stents for the treatment of myocardial infarction (page 243, right column, second paragraph), which is pertinent to claims 101 and 103.
Reddy further teaches the use of anticoagulants for the treatment of myocardial infarction (page 250, left column, second paragraph), which is pertinent to claim 102.
Reddy further teaches the use of beta blockers (i.e., an anti-ischemic agent) for the treatment of myocardial infarction (page 257, right column, third paragraph), which is pertinent to claim 100.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Spencer, Angeletti, Anderberg, Eyged, Lundberg, and Reddy to arrive at the claimed invention. As stated above, methods of using proADM to diagnose myocardial injury were known, according to the teachings of Spencer, Angeletti, Anderberg, Eyged, and Lundberg. In particular, Lundberg teaches that increased MR-proADM is associated with poor cardiovascular outcomes, and in the context of patients with sepsis. From this method, one of ordinary skill could perform a known treatment for myocardial injury, such as those described by Reddy. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
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 PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 7:00 to 3:00.
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, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the 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.
/PETER JOHANSEN/Examiner, Art Unit 1644
Prosecution Insights