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 1-4, 6 , 7, 9, 10, 13, 18 , 30 and 32 -3 4* in the reply filed on October 7, 2025 is acknowledged. Claims 8, 20-22 , 29 and 31 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , albeit claims 8, 29 and 31 are subject to rejoinder upon the allowance of their respective generic claim. * Despite Applicant’s remarks (Remarks 8), based on the election made by Applicant, claims 8, 20-22 and 31 are withdrawn, and c laim 34 will be examined. Information Disclosure Statement The information disclosure statement (IDS) submitted on May 8, 2023 is being considered by the examiner. Claim Objections Claims 1 , 3 and 18 are objected to because of the following informalities: In claim s 1 and 18 , the limitation “provide” in line 7 should be changed to “provides”. In claim 3, the limitation “sequences” in line 5 should be changed to “sequence”. Appropriate corrections are required. Claim Objections Applicant is advised that should claim 13 be found allowable, claim 34 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). In this case, claims 13 and 34 appear to be identical in scope. The claims encompass different ways of reciting identical subject matter. Claim Rejections - 35 USC § 112 In the event the determination of the status of the application as subject to AIA (or as subject to pre-AIA) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the rationale supporting the rejection would be the same under either status. The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. Claims 3, 6 , 10 and 30 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. In claim 3, clause (c) is indefinite. While clauses (a) and (b) further limit established recitations (SEQ IDs) recited in claim 1, clause (c) introduces subject matter (SEQ ID 9) not recited in claim 1. Consequently, the relationship between clause (c) and claim 1 is unclear . For example, does clause (c) intend to recite a new method step in addition to the steps recited in claim 1 (i.e. claim 3 further comprises detecting SEQ ID 9 in addition to detecting the sequences recited in claim 1) ? In claim 6, the claimed method can involve detection of a single signature peptide. In such case, it is unclear what is separated. Claim 10 is indefinite for the following reasons: The claim lacks sufficient context for many of the species recited in the claim. For example, the claim recites “determination of…tau” without specifying the relationship between tau and the rest of the method or how the determination of tau is achieved (e.g. what is the source of the tau?) . This applies to all the other species recited in the claim; The species (e) and (f) are omnibus recitations, the scope of which are unclear. For example, the metes and bounds of the limitation “other information about the subject” is unclear; and Related to 1), the scope of the limitation “determination” is unclear. For example, it is unclear how “other diagnostic tests” are “determin[ed]” or what it evens means to “determin[e] “other diagnostic tests” in the context of the claimed method. In claim 30, the limitation “is determined” is recited in passive voice. Consequently, it is unclear whether the claim intends to recite a step of performing the determination. When introducing a new method step, the verb corresponding to the step (in this instance “determine”) should be recited in active voice (e.g. “further comprising determining…”) so as to unequivocally convey that the verb is a part of the claimed method. Otherwise, the limitation “is determined” may convey intent. While claims 29 and 31 are not being examined, similar changes should be made to said claims because they are subject to rejoinder. 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. Claim s 1 -3 , 9, 10, 13, 18, 33 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Petrucelli (WO 2008/151055 A1) in view of JP 2012511154 A (“154”) and Sulzer et al. (“Sulzer”) (US 2020/0095296 A1). With respect to claim 1, Petrucelli discloses a method for diagnosing a condition characteri z ed by TDP-43 proteinopathy (see abstract) , the method comprising : treating a sample from a subject with a protease to produce peptide fragments (see abstract) , and detecting one or more signature peptides of a TDP-43 species in the treated sample (see abstract) , wherein the level of the one or more signature peptides provide s a diagnostic indicator of a subject having a condition characteri z ed by TDP-43 proteinopathy (see abstract) . The method taught by Petrucelli differs from the claimed invention in that Petrucelli does not disclose that the protease is chymotrypsin. In addition, Petrucelli does not disclose that the one or more signature peptides are each a fragment of TDP-43 that is 6 to 25 amino acids in length comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NOs: 1-3 or 52 . Regarding the use of chymotrypsin, 154 discloses a method of measuring the concentration of peptide s indicative of one or more neurological / neurodegenerative disorders (see abstract). The method comprises quantifying peptide fragments of amyloid B proteins, such as TDP-43 proteins (see [0023]) , wherein the peptide fragments are produced by cleaving the proteins using trypsin (see [0024]). In light of the disclosure of 154 and given that Petrucelli is silent regarding the identity of the protease, it would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention t o use trypsin or an analog thereof (e.g. chymotrypsin) as the protease in the method taught by Petrucelli. According to Applicant’s disclosure, trypsin and chymotrypsin are considered equivalents for the purpose of producing peptide fragments of TDP-43 protein (see line 24, p. 13) . Regarding the claimed amino acid sequences, while Petrucelli does not explicitly identify the amino acid sequences of the signature peptides being detected, the amino acid sequence of TDP-43 is well-known in the art (see [0083] and [0526], and sequences 525, 91-93 and 200-202 of Sulzer , which correspond to SEQ IDs 1-3 recited in the claim ) . Based on the disclosure of Sulzer, it would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to detect at least one of the claimed amino acid sequences when conducting the method taught by Petrucelli. With respect to claim s 2 and 3 , as discussed above, each signature peptide comprises the amino acid sequence corresponding to SEQ ID s 1 , 2 or 3 . With respect to claim 9 , the sample is a cerebrospinal fluid (see abstract of Petrucelli) . With respect to claim 10 , the claim is indefinite , as discussed above. That said, the method involves determin ing a known biomarker (presence of TDP-43 protein fragments in bodily fluid) for a condition characteri z ed by TDP-43 proteinopathy (see abstract of Petrucelli). With respect to claim 13 , the condition characterised by TDP-43 proteinopathy is amyotrophic lateral sclerosis or frontotemporal dementia (see abstract of Petrucelli) . With respect to claim 18, as discussed above (see rejection of claim 1), the combination of Petrucelli, 154 and Sulzer teaches a method of diagnosing a condition characteri z ed by TDP-43 proteinopathy in a subject , the method comprising the claimed detecting step. Petrucelli further discloses that the method can help clinicians determine proper treatment and medical care options (see line 29, pg. 1-line 2, pg. 2). Based on the disclosure, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer to the subject an appropriate treatment/ care known to address the diagnosed condition, for example administering anti-inflammatory drugs (see [0530] of Sulzer) . With respect to claim 33 , the one or more signature peptides are detected in cells isolated from blood (see line 2 4, pg. 1 of Petrucelli ) . With respect to claim 34, the level of the one or more signature peptides provide s a diagnostic indicator for differentiating a subject having amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (see abstract of Petrucelli) . Claim s 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Petrucelli in view of 154 and Sulzer as applied to claims 1 -3 , 9, 10, 13, 18, 33 and 34 above, and further in view of Streckfus et al. (“ Streckfus ”) (US 8,772,038 B2 ). With respect to claim 4 , while Petrucelli discloses that the signature peptides are detected by mass spectrometry (see lines 26-27, pg. 7), Petrucelli does not disclose the use of specifically tandem mass spectrometry. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a variation of mass spectrometry ideal for identifying sequences of peptide fragments, for example tandem mass spectrometry, as taught by Streckfus (see lines 14-16, col. 6 ). T andem (i.e. multi-stage) mass spectrometry is a form of mass spectrometry that provides more sensitivity than conventional (single stage) mass spectrometry (see line 16, col. 6) . With respect to claim 6, Streckfus further discloses combining tandem mass spectrometry with liquid chromatography to enhance peptide separation prior to analysis by tandem mass spectrometry (see lines 14-16, col. 6). In light of the disclosure, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine tandem mass spectrometry with liquid chromatography. Claim s 7 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Petrucelli in view of 154 and Sulzer as applied to claims 1 -3 , 9, 10, 13, 18, 33 and 34 above, and further in view of Anderson (US 2008/0044857 A1). With respect to claim 7 , Petrucelli does not disclose the details of the analysis via mass spectrometry. Consequently, Petrucelli does not disclose adding an internal standard to the sample. However, it is well-known in the art to add a standard sample when performing mass spectrometry for calibration . For example, Anderson discloses a method of performing quantitative proteomics via mass spectrometry, wherein the method comprises a step of adding an internal standard to a sample to be analyzed, the internal standard being used to calibrate the mass spectrometer (see [0089]). Based on the disclosure of Anderson , it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add an internal standard to the sample taught by Petrucelli for the purpose of calibrating the mass spectrometer. With respect to claim 32 , the internal standard is an isotope-labelled signal peptide (see [0089] of Anderson) . Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Petrucelli in view of 154 and Sulzer as applied to claims 1, 2, 9, 10, 13, 18, 33 and 34 above, and further in view of Van Eyk et al. (“ Van Eyk ”) (US 20 15/0212098 A1). With respect to claim 3 0 , as discussed above, the combination of Petrucelli, 154 and Sulzer teaches a step of detecting the amino acid sequences corresponding to SEQ IDs 1 and 3 (see rejection of claim 1 above) . However, the combination does not disclose a step of determining a ratio of concentration of SEQ ID 3 to the concentration of SEQ ID 1. Van Eyk teaches a method of diagnosing Alzheimer’s disease in a subject (see abstract) by determining a ratio of two or more peptide fragments of at least one biomarker of Alzheimer’s disease (see [0009]). In light of the disclosure of Van Eyk pertaining to the practicality of using a ratio of peptide fragments of at least one biomarker for the purpose of diagnosing Alzheimer’s disease, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the claimed ratio for the purpose of diagnosing the subject with a condition characterized by TDP-43 proteinopathy. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT PAUL S HYUN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8559 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:30-5:00 . 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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. /PAUL S HYUN/ Primary Examiner, Art Unit 1796