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 .
Election/Restrictions
Applicant’s election without traverse of claims 2, 6, 16, 63, 82-86 in the reply filed on 12/2/2025 is acknowledged.
Claims 1, 2, 5, 6, 12,13,15-21, 36, 63, 82-86 are pending.
Claims 1, 5, 12, 13, 15, 17-21, 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/2/2025.
Claims 2, 6, 16, 63, 82-86 have been considered on the merits herein.
Claim Rejections - 35 USC § 103
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.
Claim(s) 2, 6, 16, 82-86 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gill et al. (US20130085079, IDS) in view of the combination of Sterling (US10670611, IDS), Goix et al. (US8450069, IDS), Urdea et al. (WO2007/146229, IDS), Sharp et al. (US20120015904), Ganz et al. (JAMA, 2016, IDS), Barr et al. (WO2017011329), Shintani et al. (Sci. Reports, 2017, p. 1-14), Whitfield (Clin. Biochem. Rev, 2014, p. 15-36) and Liu et al. (Nature Comm. Vol.8, p. 2017).
Gill (US21030085079) teaches a method of detecting protein biomarkers to predict risk of developing a cardiovascular event, wherein N (the number of biomarkers) is an integer from 2-155 (0021, 0022, 0046, 0048, for example). The biomarkers are disclosed to be useful in a panel of biomarkers (0096-0100) and include MMP-12, suPAR, ATS13, Spondin-1, TFF3, and GDF11 (abstract, Table 1).
Regarding claims 16, the biomarkers are contacted with a set of capture reagents wherein each biomarker capture reagent specifically binds to a different marker being detected (0039, 0129)
Regarding claims 82-84, the capture reagent is an antibody or an aptamer (0049, 0064, 0141, 0142) and the aptamer is SOMAmer, i.e. a slow-off rate aptamer (0144)
Gill does not teach the limitations of claims 85, 86.
Sterling teaches a method of detecting protein biomarkers to predict risk of developing a cardiovascular event. The biomarkers include MMP-12 and GDF11 (abstract,col. 4, lines 61-col. 5, lines 1-5, col. 6, lines 42-col. 7, lines 1-12) .
Regarding claims 16, the biomarkers are contacted with a set of capture reagents wherein each biomarker capture reagent specifically binds to a different marker being detected (col. 8, lines 8-16).
Regarding claims 82-86, the capture reagent is an aptamer, and at least one aptamer is a slow off-rate aptamer comprising at least one to at least 10 nucleotides with modifications. The slow off-rate aptamer binds to its target protein with an off rate of (t1/2) of ≥30, 60, 90, 120, 150, 180, 210 or ≥240 minutes (col. 8, lines 8-25).
Thus, before the effective filing date of the claimed invention the use of slow off-rate aptamers having nucleotide modifications and the claimed off rate time was known for detecting CV biomarkers in a panel. Sterling discloses methods for generating aptamers having improved off-rates and modifications (see col. 22, lines 13-col. 23, lines 1-59). Thus all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Goix teaches a method of detecting protein biomarker panels for detecting cardiovascular risk assessment wherein the biomarkers include BNP, ERBB3 (col. 15, lines 21), NCAM (col. 16, lines 34), spondin-1 (col. 16, lines 7) and TREM-1 (col. 3, lines 13-15, col. 4, lines 7-10, col. 5, lines 14-23, for example) wherein the biomarkers are contacted with a capture reagent, i.e. an antibody or aptamer specific for the biomarker (col. 23, lines 56-58, col. 31, lines 28-45, for example).
Urdea (WO’229) teach a method of detecting a panel of biomarkers (N 1-1023) associated with arteriovascular events or the development thereof including inflammatory markers (p. 1, lines 20-24, p. 3, lines 23-p. 4, whole page, p. 7, whole page, p. 9, lines 1-8). The reference teaches using aptamers which specifically bind the biomarkers (p. 47, lines 1-4). The protein biomarkers to be detected include MUC16, JAM2, ANP, BNP, NCAM, and MMP12 (table 2, p. 108, 116, 117, 118, 119).
Sharp et al. (US20120015904) teach a method of detecting biomarkers (in a panel) indicative of transient ischemic attacks (TIA) as well as inflammatory markers which are associated with TIA (abstract, 0004-0010, 0032, 0187) wherein the biomarkers include NELL1 and SVEP1 (p. 54, 60).
Ganz et al. (JAMA, 2016, IDS) teaches an aptamer-based assay for detecting protein-biomarkers for cardiovascular risk wherein SIRT2 is a biomarker in the panel for predicting risk (p. 2532, whole page, see Supplemental content eTable1). Each protein in the panel is detected using an aptamer specific for the biomarker (p. 2533, Quantification of proteins section).
Barr et al. (WO2017011329) teaches a method of detecting biomarkers in a panel for risk of ischemic stroke (abstract, 0006, for example) wherein the biomarker is ANTXR2 (0054, 0116, 0118, 0119, for example). The method is disclosed to use aptamers for detection (0025, 0189, 0196, for example).
Shintani teaches that PTPRJ negatively regulates leptin leading to weight gain/obesity, which is a major risk factor for cardiovascular diseases. PRTPJ-deficient mice show enhanced insulin signaling, lower weight gain, and improved glucose and insulin tolerance. Thus, Shintani establishes that PTPRJ is a risk factor for cardiovascular diseases.
Whitfield teaches detecting biomarkers which are risk factors associated with cardiometabolic risk, i.e. the overlap of cardiovascular disease and diabetes (abstract). Whitfield teaches that CILP2 is a relevant biomarker for cardiometabolic conditions (p. 21, Biomarker assoc. section, p. 22, Table 1, p. 26, Table 3).
Liu teaches detecting markers of atherosclerosis including those linked to coronary artery calcification (CAC) and find that CACNA2D3 is significantly liked to CAC (p. 3, Results clin. Data and sample char. Section, p. 3, transcriptome signature section and Fig.1a,b d).
Thus, before the effective filing date of the claimed invention, the claimed method of detecting a level of N protein biomarkers in a sample and forming a biomarker panel to include the biomarkers BNP, ERBB3, NCAM, Spondin-1, TREM-1, MMP-12, GDF11, suPAR, ATS13, MUC16, JAM2, ANP, TFF3, NELL1, SVEP1, SIRT2, ANTXR2, PTPRJ, CILP2 and CACNA2D3 (thus N is 20 integers/biomarkers) using capture reagents including antibodies and aptamers was taught by the combination of prior art references of record. The references teach that the claimed biomarkers are markers associated with cardiovascular events or risk thereof.
The references do not teach a panel comprising each of the claimed components together in a single biomarker panel, i.e. wherein N is an integer from 8-27. However, before the effective filing date of the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine each of the claimed biomarkers in a panel, as each biomarker and combinations thereof are disclosed by the cited references above, to be biomarkers associated with cardiovascular events or risk thereof, and detectable by the claimed method. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated to combine the biomarkers together in a single biomarker panel with a reasonable expectation of successfully detecting the biomarkers and their combinations using a capture reagent which specifically binds to the biomarker because the prior art teaches capture reagent methods comprising the use of antibodies or aptamers to detect cardiovascular biomarkers in a biomarker panel. This rejection is based upon the well-established proposition of patent law that no invention resides in combining old components of known properties or function where the results obtained thereby are no more than the additive effects of the components, In re Sussman, 1943 C.D. 518. It is well known that it is prima facie obvious to combine two or more ingredients/components each of which is taught by the prior art to be useful for the same purpose in order to form a third composition which is useful for the same purpose. The idea for combining them flows logically from their having been used individually in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
Claim 63 is free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/ Supervisory Patent Examiner, Art Unit 1651