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 .
Status of the Claims
Claims 1-15 are pending in the application.
Claims 10-15 are withdrawn.
Claims 1-9 are the subject of this office action.
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 1-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (namely a law of nature/natural phenomenon and abstract ideas) without significantly more.
Claims 1-9 are directed to a process comprising predicting and/or detecting fibrinolytic insufficiency by measurement of the concentration of plasminogen and a fragment thereof in a biological sample, wherein detecting or predicting fibrinolytic insufficiency based on interpretation of biomarker measurements constitutes an abstract process that may be performed in the human mind (i.e. a practitioner uses biomarker data to draw a conclusion about fibrinolytic insufficiency).
The claims are also understood to be directed to a law of nature/natural phenomenon, wherein the correlation between levels of different biomarkers (plasminogen or a fragment thereof) and a particular disease state or risk (i.e. the naturally occurring relationship between levels of plasminogen and plasminogen fragments and fibrinolytic insufficiency) is a law of nature/natural phenomenon.
Similar concepts have been held by the courts to constitute law of nature/natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics LLC, 859, F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017), and the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of iloperidone in Vanda Pharmaceuticals Inc v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018). (See MPEP 2106.04(b)).
The correlation is naturally occurring and is a judicial exception because it exists in principle apart from any human action. The correlation itself (between plasminogen and plasminogen fragments and fibrinolytic insufficiency) therefore cannot form the basis of eligibility.
Similarly, the predicting and detecting recited in the claims constitute an abstract mental process, wherein the claims encompass a practitioner drawing a certain conclusion based on certain data, a process which may be performed in the human mind.
As such, the predicting and detecting to which the claims are directed is itself a judicial exception which cannot form the basis of eligibility. Therefore, the claims are not integrated into a practical application because they are directed to performance of the judicial exception itself.
In addition to the judicial exceptions above, the claims provide further recitations which comprise measurement of plasminogen and a fragment thereof and further limitation on sample type, subject type, associated pathology, particular plasminogen fragment measured, and general class of assay used to measure the plasminogen and fragment thereof. Neither the independent claim nor these additional limitations provided in the dependent claims are sufficient to either integrate the judicial exceptions into a practical application or TO constitute “significantly more” than the judicial exception, because they amount to mere data gathering in support of the judicial exception (i.e. in order to detect or predict the disease state one must gather data about levels of plasminogen and a fragment thereof). Wherein mere data gathering in support of a judicial exception has been identified by the courts as insignificant extra solution activity which cannot constitute significantly more than the judicial exception. See MPEP 2106.05(g). Additionally, the step of measuring plasminogen and a fragment thereof is recited at a high level of generality and is not tied to any particular machine, apparatus, or specific procedure. See MPEP 2106.04(a)(2).
Furthermore, the detection of a biomarker in a biological sample has been identified by the courts to be routine and conventional activity in the life sciences arts (see MPEP 2106.05(d)(II)), and the specific measurement of plasminogen and a fragment thereof was known, routine, and conventional in the art before the effective filing date of the claimed invention, as demonstrated by Duboscq et al (1997) Plasminogen: an important hemostatic parameter in septic patients. Thromb Haemost 77, 1090-1095.; IDS entered). Duboscq teaches detection of plasminogen in a sample using a known and commercially available chromogenic substrate assay (Chromogenix, see Pg. 1091, Col. 1, Par. 5) and teaches measurement of plasminogen fragments by the commonly used methods of SDS-PAGE electrophoresis and Western Blot (Pg. 1091, Col. 1, Par. 8). Duboscq also indicates that methods of measuring both plasminogen and plasminogen fragments in a sample were known and performed in the art prior to the publication of the reference (Abstract).
Other references including Drinane et al (Plasminogen and plasmin activity in patients with
coronary artery disease. J Thromb Haemost. 2006Jun;4{6):1288-95.; previously cited) and Buranda et al (US 2019/0242897 A1; previously cited) further teach plasminogen and plasminogen fragment detection in a sample by other methods (i.e. immunoblot, ELISA, functional assay) (Drinane, Abstract; Pg. 1289, Col. 1, last Par.-Pg. 1290, Col. 1, first Par.) (Buranda, Par. 236-238), such that the art collectively indicates that plasminogen and plasminogen fragments are well known analytes of interest and that their detection is routine such that it can be and has been performed by a number of routine and conventional methods known to one of ordinary skill in the art.
For all these reasons, the claimed elements, when taken alone or in combination, fail to include additional elements that are sufficient to either integrate the judicial exceptions into a practical application or amount to significantly more than the judicial exceptions.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Duboscq et al (1997) Plasminogen: an important hemostatic parameter in septic patients. Thromb Haemost 77, 1090-1095.; IDS entered).
Regarding claim 1, Duboscq teaches a process comprising measuring the concentration of plasminogen and at least one fragment thereof (Abstract: plasminogen levels were significantly lower in septic patients than in plasma of healthy controls or of non-septic ICU patients; Table 1; Pg. 1091, Col. 1, Par. 6: plasminogen activity determination; Pg. 1090, Col. 2, Par. 3: miniplasminogen levels in plasma of septic patients; Pg. 1091, Col. 1, Par. 9: measurement of miniplasminogen in human plasma). Wherein measurement of the concentration of plasminogen and miniplasminogen reads on measurement of plasminogen and at least one fragment thereof.
Duboscq teaches that the detection of plasminogen and plasminogen fragments can be used to detect fibrinolytic insufficiency associated to pathologies with NETs with/without DIC such as sepsis and septic shock (Pg. 1093, Col. 2, Par. 2: decreased levels of plasminogen pointing to a hypofibrinolytic state; Pg. 1092, Col. 1, Par. 1: plasminogen may be used as a biomarker for predicting the severity of septicemia, wherein plasminogen levels below particular threshold could be used to predict death from septicemia with 90.5% specificity and 66.7% accuracy; Abstract: the study concluded that plasminogen concentrations were significantly lower in plasma of septic patients as compared to the plasma of healthy controls or non-septic intensive care patients from the same unit).
Regarding claims 2-3 and 8, Duboscq further teaches the process wherein pathologies are infectious or non-infectious and wherein pathologies associated with NETs comprise sepsis and septic shock, and wherein the biological sample originates from a patient with septic shock (Pg. 1090, Col. 2, last Par.-Pg. 1091, Col. 1, Par. 1: blood samples were taken from 45 septic ICU patients, where 18 of the 45 were non-survivors) (wherein 18 non-survivors with septicemia are understood to include patients with septic shock).
Regarding claim 4, Duboscq further teaches the process wherein the concentration of plasminogen is measured by a functional assay, an immunoassay, a cellular immunoassay, flow cytometry, or colorimetric method (Pg. 1091, Col. 1, Par. 6: coagulation factor levels were determined by functional methods. Activities of antithrombin III, plasminogen, and alpha-2-antiplasmin were measured using chromogenic substrate assays).
Regarding claim 5, Duboscq further teaches the process wherein the plasminogen fragment is measured by proteomic analysis, antigenic assay, immunoassay, or flow cytometry (Pg. 1091, Col. 1, Par. 8: samples analyzed by SDS-PAGE electrophoresis and Western Blot using monoclonal antiplasminogen antibody with high sensitivity for human miniplasminogen). It is noted that Duboscq teaches a non-elected species of claim 5 and does not teach the elected species of proteomic analysis, though the teaching of the non-elected species is included here for completeness of the record.
Regarding claim 6, Duboscq further teaches the process wherein the biological sample is selected from the group comprising a blood sample and a plasma sample (Abstract: plasminogen concentration in plasma; Pg. 1090, Col. 2, last Par.-Pg. 1091, Col. 1, Par. 6: collection of blood samples and preparation of plasma samples).
Regarding claims 7 and 9, Duboscq further teaches the process comprising measuring plasminogen fragment miniplasminogen (K5-SP) (Pg. 1090, Col. 2, Par. 3: miniplasminogen levels in plasma of septic patients; Pg. 1091, Col. 1, Par. 9: measurement of miniplasminogen in human plasma. Control miniplasminogen was obtained by limited digestion of purified plasminogen with human leukocyte elastase; Fig. 3; Pg. 1093, Col. 1, Par. 1).
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 5 is rejected under 35 U.S.C. 103 as being unpatentable over Duboscq et al (1997) Plasminogen: an important hemostatic parameter in septic patients. Thromb Haemost 77,
1090-1095.; IDS entered), as applied to claim 1 above, and further in view of van der Plas et al (A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis. PLoS One. 2014 Mar 19;9(3):e92096; previously cited).
Regarding claim 5, Duboscq teaches the process of claim 1 and teaches a non-elected species of claim 5, as described above, but does not teach the elected species of proteomic analysis. Duboscq teaches that plasminogen fragment is measured in samples by assays which detect the concentration and molecular weight of miniplasminogen in the sample (Pg. 1093, Col. 1, Par. 1; Fig. 3; Pg. 1091, Col. 1, Par. 8).
Regarding claim 5, van der Plas teaches that proteomic analysis/LC-MS can be used to detect and determine masses of plasminogen fragments (Fig. 6; Pg. 2, Col. 2, Par. 5-6-Pg. 3, Col. 1, first Par.: digested fragments detected by LC-MS).
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 the process taught by Duboscq to use proteomic analysis/LC-MS for the detection of plasminogen fragments as taught by van der Plas. Such a modification amounts to simple substitution of known methods to achieve predictable and successful results since both the detection taught by Duboscq and the detection taught by van der Plas are suitable methods which are well known in the art for detecting concentration of mass of proteins and protein fragments such as plasminogen and plasminogen fragments.
Response to Arguments
Applicant’s arguments filed 19 September 2025 have been fully considered.
Previous rejection under 112(b) and 112(d) are overcome by the amendments to the claims and are withdrawn.
Regarding the prior art rejections under 102 and 103, Applicant argues that Dubosq does not disclose measurement of plasminogen and a plasminogen fragment, but rather discloses measurement of miniplasminogen and a degraded form of plasminogen of 38 kDa. This argument is not persuasive, because while Duboscq does disclose measurement of a degraded 38 kDa plasminogen by Western Blot, it also discloses measurement of plasminogen by other methods (e.g. Pg. 1091, Col. 1, Par. 6: plasminogen measurement by chromogenic assay).
Applicant further argues that Duboscq does not appropriately teach detection of plasminogen fragments in the method. This argument is not persuasive because Duboscq explicitly teaches detection of miniplasminogen (K5-SP), a plasminogen fragment specifically recited in the claims.
Applicant further argues that Duboscq does not appropriately teach a diagnostic or predictive relationship between the concentration of plasminogen and plasminogen fragments and fibronolytic insufficiency. This argument is not persuasive because Duboscq teaches a method comprising measurement of concentration of plasminogen and a plasminogen fragments and teaches that the resulting concentrations may be used to predict or detect fibrinolytic insufficiency associated to pathologies with NETs with or without DIC (e.g. sepsis).
Applicant further argues unexpectedly improved results. This argument is not persuasive for overcoming a 102 rejection. Additionally, applicant has not specifically described what would be expected from the teachings of the prior art and therefore what is unexpected about results achieved with the instant invention. Additionally, as discussed above, the prior art teaches a known relationship between plasminogen concentration and fibrinolytic insufficiency associated with pathologies with NETs, such that the results of the present invention do not appear to be unexpected.
Regarding the 101 rejection, applicant argues that the claim does integrate the judicial exception into a practical application. This argument is not persuasive for the reasons discussed in the rejection above. Additionally, it is noted that the judicial exception is only integrated into a method of prognosis/diagnosis wherein the naturally occurring association between biomarkers and disease states is used to draw a judgment or conclusion (mental step/abstract idea), which is itself a judicial exception and thus does not comprise integration of the judicial exception into a practical application.
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 ELLIS LUSI whose telephone number is (571)270-0694. The examiner can normally be reached M-Th 8am-6pm ET.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
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