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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 29, 2025 has been entered.
Status of claims
Claims 1-8, 10-12, 14, and 17-22 were pending. Claims 1-8, 10-12, 14, and 17-20 were withdrawn. No claim amendments have been made.
Claims 21-22 are examined herein.
Claim Objections
Claim 22 is objected to because:
Claim 22 recites “(Prostate Specific Antigen) PSA”. Should be “PSA (Prostate Specific Antigen)”.
Appropriate correction is required.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Giovarelli et al. (WO 2017/153869) in view of Batra et al. (IDS; J Biomark. 2014; 2014:321680) and Eccleston et al. (IDS; WO 2016/067029), for reasons of record which are reiterated herein below.
Regarding claims 21-22, Giovarelli teaches IL-6 and IL-8 as biomarkers for in vitro diagnosis of prostate cancer. Specifically, the reference teaches “analysis on urine samples of the individual biomarkers IL-6, OPN, VEGF, TGF-β, IL-17, GM-CSF, IP-10, PDGF, CCL5, Eotaxin and IL-8 is already indicative of prostate cancer” (pg. 13, line 36 and pg. 14, lines 1-2). Fig. 4 and 6 teach ROC curves generated from the results of IL-6 and IL-8 detection; therefore, Giovarelli teaches reagents to detect IL-6 and IL-8.
Additionally, Giovarelli teaches motivation for combining several biomarkers “the simultaneous analysis of several biomarkers allows even more reliable identification of patients with prostate cancer” (pg. 14, lines 3-5).
Giovarelli does not specifically teach reagents to detect histone H3.1 and PSA.
Regarding claims 21-22, Batra teaches PSA and IL-6 as biomarkers of prostate cancer detectable by commercially available kits (Abstract); therefore, Batra teaches reagents to detect PSA and IL-6.
Giovarelli and Batra do not teach reagents to detect histone H3.1.
Regarding claims 21-22, Eccleston teaches the use of histone binding agents for detecting, isolating and/or purifying cell free nucleosomes of tumor origin (Abstract). Eccleston also teaches histone H3.1 as prostate cancer biomarker. Specifically, Eccleston teaches that circulating levels of nucleosomes containing histone H3.1 differ considerably between healthy subjects and subjects with prostate cancer (pg. 9, par. 2 and Fig. 6 (iii)(a)); therefore, Eccleston teaches reagents to detect histone H3.1.
Claims 21 and 22 do not specify what type of sample this panel needs to work in. Given broadest interpretation of the claim, the biomarkers could be detected in different samples and still read on the claim since there's no mention of sample processing, or how the panel is being used in an assay.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined reagents to detect IL-6 and IL-8 biomarkers of Giovarelli with reagents to detect PSA and IL-6 biomarkers as taught by Batra, and with reagents to detect histone H3.1 biomarker as taught by Eccleston, in order to provide a panel of reagents for diagnosing and/or monitoring prostate cancer. One having ordinary skill in the art would have been motivated to combine the reagents because Giovarelli teaches motivation for combining several biomarkers “the simultaneous analysis of several biomarkers allows even more reliable identification of patients with prostate cancer” (pg. 14, lines 3-5).
Additionally, MPEP 2144.06 provides "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the reagents for several known biomarkers of prostate cancer in one panel of reagents for identification of patients with prostate cancer.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because the reagents to detect individual biomarkers in the panel can be used in separate reactions for each biomarker and the prior art references have already established that the individual reagents are successful.
Response to Arguments
Applicant’s after-final arguments filed September 2, 2025 have been fully considered. No additional arguments had been submitted with the RCE filed September 29, 2025.
Applicant argues that “neither Giovarelli, Batra, nor the combination thereof suggests detecting nucleosome markers, let alone the histone isoform H3. l, as specifically claimed” (pg. 2, last par.), “an ordinarily skilled artisan would have had no reasonable expectation of success in combining Giovarelli with Batra and Eccleston because the biomarkers suggested by Giovarelli are contemplated for use in urinary analysis, whereas Batra and Eccleston describe biomarkers in blood samples” (pg. 3, par. 1), “Batra makes no mention of the possibility of testing PSA in urine, nor does Eccleston disclose or suggest the possibility of measuring histone H3.l in urine. There is therefore no suggestion in either reference that the histone H3. l and PSA biomarkers detected in blood may be combined with the urinary biomarkers disclosed in Giovarelli with any reasonable expectation of success” (pg. 3, par. 3), and “one of ordinary skill in the art would have had no reasonable expectation of success that detecting interleukins IL-6 and IL-8, and histone H3. l in the same bodily fluid” (pg. 4, par. 6).
The arguments are not persuasive because Giovarelli does not teach away from detecting IL-6 and IL-8 in blood. Giovarelli merely states that it is “decidedly preferable to identify prostate cancer biomarkers that can be detected in the urine instead of in the plasma or serum” (pg. 3, lines 3-4). The term “preferable” does not mean impossible or undesirable.
Giovarelli does not teach away because disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004) (MPEP 2123.II).
Batra teaches detection of PSA in blood (pg. 2, col. 1, par. 1) and IL-6 in serum (pg. 3, col. 2, par. 1). Additionally, Batra teaches biomarkers detected in blood: Prostate Stem Cell Antigen (pg. 4, col. 2, par. 2), Circulating Tumor Cells (pg. 6, col. 1, par. 3), and RNA biomarker PCA3 (pg. 6, col. 2, par. 1); and biomarkers detected both in urine and blood: sarcosine (pg. 2, col. 2, par. 3), micro RNA (pg. 4, col. 2, par. 3), exosomes (pg. 5, col. 1, par. 4), AMACR and DNA methylation (Fig. 1). As such, Batra teaches a number of biomarkers successfully detected in blood and/or urine. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success of detecting prostate cancer biomarkers in either blood or urine.
Additionally, it is recognized in the field of immunoassays that the same antibodies are usually suitable for analyte detection in different kinds of samples, such as blood, serum, plasma, urine, CSF, etc. Each kind of sample may require fine tuning of the assay conditions and component concentrations to achieve the best possible performance, but usually an antibody successful in an assay in blood, serum, plasma, urine, or CSF gives a reasonable expectation of success of detecting the same biomarker in the other kinds of samples. This is an observation based on a large body of practical experience in the field of immunoassays.
Finally, claims 21 and 22 do not specify what type of sample this panel needs to work in. Given broadest interpretation of the claim, the biomarkers could be detected in different samples and still read on the claim since there's no mention of sample processing, or how the panel is being used in an assay.
Applicant argues that “one of ordinary skill in the art would understand from Giovarelli that IL-6 and IL-8 detection in a blood, serum or plasma sample cannot determine whether the subject has a pathological condition, let alone determine the type of pathological condition” (pg. 3, par. 2). The argument is not persuasive because Applicant is arguing limitations which are not claimed. It is noted that a presence and a type of a pathological condition are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that “there is no suggestion that detecting them in combination would provide an effective or useful result” (pg. 4, par. 1) and “Giovarelli provides no motivation to combine secreted, activating factors, namely IL-6 and IL-8, with passive biomarkers derived from cell death, namely histone isoform H3.1” (pg. 4, par. 5). The argument is not persuasive because as presented above in 103 rejection, MPEP 2144.06 provides "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Therefore, it would have been obvious to combine the reagents for several known biomarkers of prostate cancer in one panel of reagents for identification of patients with prostate cancer.
Additionally, Giovarelli teaches motivation for combining several biomarkers “the simultaneous analysis of several biomarkers allows even more reliable identification of patients with prostate cancer” (pg. 14, lines 3-5). It would have been obvious to combine the reagents for several known biomarkers, such as IL-6, IL-8, and histone isoform H3.1.
By reciting “high specificity and sensitivity scores shown in the Examples (e.g. Example 4) of the instant application” and “more accurate information relating to the clinical risk” (pg. 4, par. 6), Applicant is arguing limitations which are not claimed. It is noted that information relating to the clinical risk, high specificity and sensitivity scores are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677