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 .
DETAILED ACTION
1. The Amendment filed October 01, 2025 in response to the Office Action of June 04, 2025 is acknowledged and has been entered. Claims 1-27, 29, 30, 33-35, 37-38, 40-57 and 59-62 have been cancelled. Claim 28 has been amended.
2. Claims 28, 32, 36, 39 and 58 are currently being examined.
Priority
3. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/413,386, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of October 26, 2017 for claims 28, 32, 36, 39 and 58 because the claims as currently constituted recite A method for detection of a-synuclein RNA in a population of exosomes, comprising: (A) providing a cerebrospinal fluid (CSF) sample obtained from a subject, said sample comprising exosomes, (B) performing immuno-isolation of the exosomes from the sample of step (A) using antibodies specific for CACNA2D1 or SYT1, (C) extracting RNA from the exosomes isolated in step (B), so as to provide exosomal RNA, and (D) determining the expression level of a-synuclein RNA molecules in the exosomal RNA extracted at step (C) by RNA sequencing (RNA-seq), array analysis, or reverse transcription polymerase chain reaction (RT-PCR. A review of Application No. 62/413,386 does not reveal the claimed method. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
New Grounds of Rejection
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.
4 Claim(s) 28, 32, 36 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0309791 A1 (Goetzl et al. Oct. 1, 2020, effectively filed May 6, 2016), “Goetzl-979” in view of Gui et al. (Oncotarget Oct. 15, 2015, 6(35): 37043-37053, of record), “Gui”.
Goetzl-979 teaches methods of diagnosing or prognosing a neurodegenerative disorder in a subject, identifying a subject at risk of a neurodegenerative disorder, or prescribing a therapeutic regimen or predicting benefit from therapy in a subject having a neurodegenerative disorder, comprising: assaying the level of one or more biomarkers in a biological sample from the subject; and diagnosing or prognosing a neurodegenerative disorder in a subject, identifying a subject at risk of a neurodegenerative disorder, or prescribing a therapeutic regimen or predicting benefit from therapy in a subject having a neurodegenerative disorder based on the levels of the biomarker, wherein at least one of the one or more biomarkers is synaptotagmin 1 (SYT1) in cerebrospinal fluid. See ¶¶ 0005, 0006, 0009, 0011, and 0033, claim 26 and Table 1.
Goetzl-979 teaches a method comprising: a) obtaining a biological sample comprising vesicles from a subject; b) isolating vesicles, including exosomes, from the biological sample; and c) detecting one or more biomarkers from the isolated vesicles, wherein at least one of the one or more biomarkers is synaptotagmin 1 in cerebrospinal fluid. See ¶¶ 0005, 0006, 0009 and 0011, and 0033, claim 26 and Table 1.
Goetzl-979 teaches measuring the levels of α-synuclein in the exosomes. See ¶¶ 0005, 0006, 0009 and 0011 and claim 32.
Goetzl-979 teaches using antibodies to purify the exosome vesicle with magnetic beads. See ¶¶ 0007-0008, 0035, 0038 and 0065.
Goetzl-979 teaches that SYT1 is exosomal synaptic protein. See ¶¶ 0017 and 0021 Figs. 1B and 5B.
Goetzl-979 teaches that antibodies to SYT1 can be made to bind an exosome. See ¶¶ 0058 and 0060.
Given that Goetzl-979 teaches using antibodies to purify the exosome vesicle and teaches that antibodies to SYT1 can be made to bind an exosome, it would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Goetzl-979 and use the antibodies to SYT1 to purify exosomes given that SYT1 is present on exosomes as taught by Goetzl-979.
Goetzl-979 teaches measuring the RNA levels of the biomarkers in the exosome vesicles using PCR or sequencing. See ¶¶ 0005, 0007, 0008, 0011, 0025, 0043, and 0045 and claim 29.
Goetzl-979 teaches as set forth above, but does not teach detecting a-synuclein RNA with RT-PCR.
Gui teaches that a-synuclein mRNA detected by quantitative RT-PCR was differentially expressed in cerebrospinal fluid (CSF) exosomes from Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients. See abstract, p. 37047- Messenger RNA transcripts and long non-coding RNAs were differentially expressed in CSF exosomes in PD and AD patients and Fig. 3A.
Gui teaches these data demonstrated that CSF exosomal RNA molecules are reliable biomarkers with fair robustness in regard to specificity and sensitivity in differentiating PD from healthy and diseased (AD) controls.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Goetzl-979 and Gui and detect a-synuclein RNA with RT-PCR from cerebrospinal fluid exosomes in the methods of Goetzl-979 because Goetzl-979 teaches measuring the levels of a-synuclein RNA in SYT1 immune isolated cerebrospinal fluid exosomes for the diagnosis of a neurodegenerative disorder, including AD and PD (¶¶ 0005-0007), and Gui teaches that a-synuclein mRNA detected by quantitative RT-PCR was differentially expressed in CSF exosomes from Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients. One would have been motivated to detect the a-synuclein mRNA because Gui teaches that cerebrospinal fluid exosomal RNA molecules are reliable biomarkers with fair robustness in regard to specificity and sensitivity in differentiating PD from healthy and diseased controls.
5. Claim(s) 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0309791 A1 (Goetzl et al. Oct. 1, 2020, effectively filed May 6, 2016), “Goetzl-979” in view of Gui et al. (Oncotarget Oct. 15, 2015, 6(35): 37043-37053, of record), “Gui” as applied to claims 28, 32, 36, and 58 above, and further in view of Soreq et al. (PLOS Computational Biology March 2014, 10(3): e1003517, pp. 1-22, of record), “Soreq”.
Goetzl-979 and Gui teach as set forth above, but do not teach sequencing all extracted exosomal RNA.
Soreq teaches that RNA-Seq analysis is robust means to identify novel biomarkers in blood cell transcripts. See abstract.
Soreq teaches using whole transcriptome RNA-Seq analysis to identify known and novel alternative splicing events in leukocytes from Parkinson’s Disease (PD) patients. Soreq teaches identification PD-induced changes in 13 of over 6,000 detected long non-coding RNAs. Soreq teaches that using quantitative RT-PCR detected PD associated changes in the long non-coding RNAs. See abstract and Figs. 1-3, 5, and 6.
Soreq teaches that RNA-Seq analysis method is a comprehensive new resource for understanding disease transcriptome modifications in PD and other neurodegenerative diseases.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Goetzl-979, Gui and Soreq and use the RNA-Seq analysis method of Soreq in the method of Goetzl-979 and Gui to analyze the transcriptome of the exosomes isolated in the method of Goetzl-979 and Gui to identify novel biomarkers in PD and other neurodegenerative diseases. One would have been motived to identify novel biomarkers in the isolated the exosomes to optimize the diagnosis of PD and other neurodegenerative diseases.
Conclusion
6. All other objections and rejections recited in the Office Action of June 04, 2025 are withdrawn in view of Applicant’s amendments and arguments.
7. No claims allowed.
8. 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 extension fee 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 date of this final action.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet L Epps-Smith can be reached on 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Peter J Reddig/
Primary Examiner, Art Unit 1642