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 13, 2025, has been received. By way of this submission, Applicant has amended claims 1, 6, and 13, and cancelled claim 2.
Claims 1 and 3-42 are pending in the application. Claims 9 and 37-42 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed June 10, 2025.
Claims 1, 3-8, and 10-36 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated August 13, 2025.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at pages 1, 3, 4, and 47. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
This objection is maintained.
Claim Objections
Claims 1 was previously objected to due to the presence of minor informalities.
Applicant's amendments to the claims have addressed this issue, and this objection is hereby withdrawn.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-8, 10-19, 22-24, and 26-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims recite a natural phenomenon, a correlation between biomarker levels and least one of prognosis, risk assessment and diagnosis of a MACCE in combination with an infection in a patient. This judicial exception is not integrated into a practical application because the claimed data gathering steps do not adda meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because quantifying levels of a biomarker is a well-understood, routine, conventional activity in laboratory technique, and therefore insufficient to amount to an inventive concept.
Applicant argues that no natural correlation is recited in the amended claims, and the claimed treatment adds "something more" which transforms the judicial exception into a patentable invention.
Applicant's arguments have been considered fully but are not found to be persuasive.
The claims still recite the natural correlation of the relationship between biomarker levels and prognosis, risk assessment or diagnosis of a MACCE in combination with infection.
The measuring steps recited in amended steps ii) and iii) are insignificant extra-solution activity, as they rely upon well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). MPEP 2106.05 (II).
Amended step iv) recites the treatment of the patient with an anti-infective therapy (i.e., antibiotics), a highly general treatment well-known in the art for the treatment of infection. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, does not qualify as "significantly more". than the exception. MPEP 2106.05(I)(A).
This rejection is therefore maintained.
Applicant is invited to incorporate the subject matter of claim 20 into claim 1 in order to obviate this rejection.
Claim Rejections - 35 USC § 112
Claims 1-8 and 10-36 were previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant's amendments to the claims have addressed this issue, and this rejection is hereby withdrawn.
Claims 6, 12-13, 16-18, and 22-24 were previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant's amendments to the claims have addressed this issue, and this rejection is hereby withdrawn.
Claim 6 was previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant's amendments to the claims have addressed this issue, and this rejection is hereby 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, 3-8, 10, 12, 16-20, 22-24, 27-29, 31-32, and 34-36 are rejected under 35 U.S.C. 103 as being unpatentable over Valkirs (US20030109420A1) in view of Spencer (US20170009297A1).
Claims 2, 11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Valkirs and Spencer as applied to claim 1 above, and further in view of Ekeloef (British Journal of Anaesthesia, 2016, 117(5), pp. 559-568, cited in IDS).
Applicant argues that the cited references teach every aspect of the invention as claimed; specifically, the references do not teach patients who have undergone gastrointestinal surgery or treatment with early preemptive anti-infective therapy.
Applicant's arguments in view of the amendments to the claims have not addressed this issue fully. In the interest of compacting prosecution, the above rejections are withdrawn, and the following new grounds of rejection are issued, necessitated by Applicant's amendment to the claims:
Claims 1, 3-8, 10-12, 16-20, 22-24, 27-29, 31-32, and 34-36 are rejected under 35 U.S.C. 103 as being unpatentable over Valkirs (US20030109420A1) in view of Spencer (US20170009297A1) and Ekeloef (British Journal of Anaesthesia, 2016, 117(5), pp. 559-568, cited in IDS).
Valkirs teaches a method of diagnosing acute coronary syndrome (i.e., myocardial infarction, see para. 0004) by analyzing a test sample obtained from a patient for the presence or amount of one or more markers for myocardial injury, and that said markers can be compared to a diagnostic level that is associated with the diagnosis, prognosis, or differentiation of acute coronary syndrome (ACS) (para. 0015).
Valkirs further teaches that markers may be combined to increase the predicative value of the analysis, such as one or more specific markers for myocardial injury can be combined with one or more non-specific markers for myocardial injury (para. 0017).
Valkirs further teaches that one such biomarker may be cardiac troponin T (cTnT) (para. 0021), which is pertinent to claims 1 and 8. As Applicant's specification states that the diagnostic criteria for MINS is a postoperative troponin elevation judged to be due to myocardial ischemia (page 3), Valkirs also teaches MINS.
Valkirs further teaches that one such biomarker may be B-type natriuretic peptide (BNP) or its precursor, NT-proBNP (para. 0056), which is pertinent to claims 3-5.
Valkirs further teaches cardiac troponin may be increased in conjunction with sepsis (para. 0058-0059).
Valkirs further teaches that this method is useful for determining a treatment regimen (para. 0037).
Valkirs further teaches that high levels of cardiac troponin T are associated with electrocardiographic changes (para. 0151), and that myocardial infarction can be diagnosed by electrocardiography Q-waves (para. 0007), which is pertinent to claim 6.
Valkirs further teaches that detection of biomarkers may also include fragments thereof (para. 0018), which is pertinent to claim 7.
Valkirs further teaches that the patient may be at least 65 years old (para. 0131), which is pertinent to claim 10.
Valkirs further teaches a plurality of test samples taken at different times (claim 56), which is pertinent to claim 19.
Valkirs further teaches that the level of an indicator can be compared to a threshold level (para. 0030), which is pertinent to claim 20.
Valkirs further teaches evaluation of myocardial infarction and mortality after 30 days (para. 0136), which is pertinent to claims 22-23.
Valkirs further teaches that changes in marker levels are relevant to the prognostic or diagnostic function of the test (para. 0031 and 0035), which is pertinent to claim 29.
However, Valkirs does not teach treatment with antibiotics or gastrointestinal surgery.
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).
Spencer further teaches that samples may be taken from patients who were undergoing elective abdominal surgery (para. 0060-0062).
Spencer further teaches that samples may be taken multiple times before and after surgery and several days apart from patients in a hospital (para. 0061), which is pertinent to claims 12 and 16-18.
Spencer further teaches that monitoring biomarker levels is useful to predict and monitor the development of sepsis (para. 0039).
Spencer further teaches administration of antibiotics (para. 0070).
Spencer further teaches that different thresholds may be applied to different samples (para. 0098) and different time points (para. 0069), which is pertinent to claims 27 and 28.
Spencer further teaches comparing the data with reference data (para. 0048), which is pertinent to claim 31.
Ekeloef teaches that troponin elevation is a predictor of major adverse cardiac events and postoperative mortality in patients undergoing non-cardiac, non-vascular surgery (abstract).
Ekeloef further teaches that the patient may undergo elective surgery, and may include gynecological (i.e., reproductive system) surgery.
Ekeloef further teaches that treatment of pain may prevent postoperative troponin elevation and major cardiac events (page 565), which is pertinent to claim 11.
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 Valkirs, Spencer, and Ekeloef to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of Valkirs, Spencer, and Ekeloef are concerned with the measurement of biomarkers to assess patients following surgery. As Valkirs teaches, cardiac troponin may be increased in conjunction with sepsis. Valkirs also teaches that comparing levels of biomarkers such as cardiac troponin and NT-proBNP is useful to assess acute coronary syndrome, which is a major adverse cardio-or cerebrovascular event (see pages 2 and 11 of the instant specification). Spencer teaches that patients who have a marker for sepsis may be treated with antibiotics. Ekeloef further teaches that such a method is useful in diagnosing patients with gynecological surgery. One of ordinary skill could apply the method of Valkirs and Spencer to the patient population of Ekeloef by known methods, with each component of the combination performing its known, usual function, and the combination would produce nothing more than predictable results.
In response to Applicant's arguments, Applicant's specification at page 17 states that reproductive system surgery (i.e, gynecological surgery) is within the scope of gastrointestinal surgery.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Valkirs, Spencer, and Ekeloef as applied to claim 1 above, and further in view of Cahill (International Scholarly Research Notices, Vol. 2011, Article ID 403130).
The teachings of Valkirs, Spencer, and Ekeloef have been discussed supra. However, none of Valkirs, Spencer, and Ekeloef teach surgery of the intestines.
Cahill teaches that monitoring levels of troponin and B-type natriuretic peptide (BNP) is useful in predicting myocardial injury and infarction after gastrointestinal surgery (page 4, left column, second through fourth paragraph).
Cahill also includes colorectal surgery as part of this patient cohort (page 2, left column, second paragraph). According to Applicant's specification at page 17, rectal surgery is within the scope of large intestine surgery, which in turn is within the scope of gastrointestinal surgery.
Cahill also teaches that the surgery may be open (page 2, 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 Valkirs, Spencer, Ekeloef, and Cahill to arrive at the claimed invention. As stated above, methods of using troponin as a biomarker to assess patients with major cardiac events after surgery were known. Cahill gives further guidance as to the cohort of gastrointestinal surgery patients being suitable for such an assessment. One of ordinary skill could apply the method of Valkirs, Spencer, and Ekeloef to the patient population of Cahill by known methods, with each component of the combination performing its known, usual function, and the combination would produce 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, 8:00 to 4:00.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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