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 .
The claims filed 10/8/2025 are under consideration.
The amendments and arguments presented in the papers filed 10/8/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 4/23/2025 listed below have been reconsidered as indicated.
a) Any objection and/or rejection of claims 2, 3, 10, 12, 13 and 16-18 are withdrawn as being moot in view of the cancellation of the claims.
b) The rejections of claims 1-3, 8, 10, 12-13 and 16-18 under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more are withdrawn in view of the amendments.
c) The rejections of claims 1-3, 8, 10, 12-13 and 16-18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement are withdrawn in view of the amendments to the claims.
d) The rejections of claims 1-3, 8, 10, 12-13 and 16-17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendments to the claims.
e) The rejection of claim 16 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn in view of the amendments to the claims.
f) The rejections of claim(s) 1-3, 8, 10, 12-13 and 16-18 under 35 U.S.C. 103 as being unpatentable over Voora (Journal of the American College of Cardiology. 2013. 62(14):1267-1276 and Appendices) in view of Bray (BMC Genomics. 2013. 14:1, 15 pages) are withdrawn because Voora is silent regarding the analysis of splice variants in platelets.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Claim Interpretation
Claim 1 limits the biological sample to consisting of isolated platelets, meaning that the platelets have been altered or removed from the natural state (p. 17, lines 5-9). For example, the platelets may be partially or completely separated from the coexisting material of its natural state (p. 17, lines 6-8).
Claim 1 requires “RNA sequencing of the transcriptome of isolated platelets” as part of “measuring alternative splicing events” in a plurality of genes present in a plurality of biological samples from a plurality of healthy subjects. The claim requires at a minimum the RNA sequencing of at 2 genes from 2 samples from 2 healthy subjects. The claim further requires “analyzing the alternative splicing events of the plurality of genes from the RNA sequencing of the transcriptome of the isolated platelets. The amount of data to be analyzed from RNA sequencing the transcriptome of at least 4 samples of isolated platelets cannot practically be performed in the human mind, even with the aid of pen and paper. The human mind is not practically equipped to analyze sequencing data representing the entire transcriptome of isolated platelets.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nassa (Scientific Reports. 2018. 8:498 and Supplementary Information; cited on the 1/18/2023 IDS).
Regarding claim 1, Nassa teaches determining the presence of alternative splicing events of a plurality of genes in the transcriptome of samples using RNA-seq (Figure 4; and p. 10, RNA sequencing and data analysis). The samples used by Nassa are a plurality of “isolated” or purified platelets from 15 healthy volunteers (p. 9, Platelet purification and activation). The biological samples are obtained at two different time points: a first aliquot immediately processed and used as control (baseline: T0); and one of two aliquots treated with Collagen (COLL, 60 μg/mL) or Thrombin Receptor Activating Peptide (TRAP 25 μM) under continuous stirring for 120 minutes at 37 °C before processing (p. 9, Platelet purification and activation).
Nassa teaches analyzing for alternative splice events of genes from the transcriptome of the isolated platelets using FASTQC and a IRFinder tool (Figure 4; and p. 10, RNA sequencing and data analysis).
Nassa teaches identifying one or more genes with the lowest number of alternative splice events (e.g., “most stable genes” that were not spliced before and after activation) and those with the highest number of alternative splice events (e.g., “least stable genes” that were spliced after activation) (Figure 4).
Nassa further teaches calculating a repeatability for the “stable genes” by calculating and reporting an IR ratio (p. 10, RNA sequencing and data analysis; and Figure 4). For example, Nassa teaches “Most of the [IR] values fall near to 0 (orange-red), indicating intron reduction (loss) after platelet activation”. The values falling around >0.8 (Figure 4), represent the repeatability for the “stable genes”.
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.
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, 8, 10, 12-13 and 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nassa (Scientific Reports. 2018. 8:498 and Supplementary Information) in view of Simon (Blood. 2014. 123(16):e37-e45; cited on the 1/18/2023 IDS).
Regarding claims 8 and 19, Nassa teaches determining the presence of alternative splicing events of a plurality of genes in the transcriptome of samples using RNA-seq (Figure 4; and p. 10, RNA sequencing and data analysis). The samples used by Nassa are a plurality of “isolated” or purified platelets from 15 healthy volunteers (p. 9, Platelet purification and activation). The biological samples are obtained at two different time points: a first aliquot immediately processed and used as control (baseline: T0); and one of two aliquots treated with Collagen (COLL, 60 μg/mL) or Thrombin Receptor Activating Peptide (TRAP 25 μM) under continuous stirring for 120 minutes at 37 °C before processing (p. 9, Platelet purification and activation).
Nassa teaches analyzing for alternative splice events of genes from the transcriptome of the isolated platelets using FASTQC and a IRFinder tool (Figure 4; and p. 10, RNA sequencing and data analysis).
Nassa teaches identifying one or more genes with the lowest number of alternative splice events (e.g., “most stable genes” that were not spliced before and after activation) and those with the highest number of alternative splice events (e.g., “least stable genes” that were spliced after activation) (Figure 4).
Nassa further teaches calculating a repeatability for the “stable genes” by calculating and reporting an IR ratio (p. 10, RNA sequencing and data analysis; and Figure 4). For example, Nassa teaches “Most of the [IR] values fall near to 0 (orange-red), indicating intron reduction (loss) after platelet activation”. The values falling around >0.8 (Figure 4), represent the repeatability for the “stable genes”.
Nassa does not teach the additional elements specific to claim 8 or claim 19.
However, Simon provides for an analysis of mRNA in platelets associated with age (Title; and Abstract).
Regarding claim 8, Simon teaches repeating a process with more samples to validate a finding (Abstract; and p. e39, Validation of mRNA and miRNA ranks).
It would have been prima facie obvious to the ordinary artisan to have repeated the process of Nassa with additional samples in order to validate the observations.
Regarding claim 19, Simon teaches evaluating samples based on age and observed differences in mRNA in platelets (p. e39, mRNAs and miRNAs DE by age; and Figure 3).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have modified the method of Nassa by repeating the analysis with samples that are “aged” relative to the original sample. For example, Simon teaches ages of samples from 18 y to 46 years. One would be motivated to make such a modification as it would allow one to see if the splice variants observed by Nassa are stable with age.
Conclusion
No claims allowed.
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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682