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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on October 27, 2025.
Currently, claims 1-6, 12-13, 17-22, 28-29, and 32-36 are pending in the instant application. Claims 3-4 and 6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, wherein applicant’s elected species is miR-142-3p in the reply filed on March 19, 2025. Accordingly, claims 1-2, 5, 12-13, 17-22, 28-29, and 32-36 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112
Claims 1-2, 5, 12-13, 17-22, and 28-29 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on April 25, 2025 and for the reasons set forth below.
Applicant's arguments filed on October 27, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims as currently amended comply with the written description requirement. Contrary to applicant’s argument, the claims as currently amended do recite the broad limitation of “fluid sample” in “obtaining the fluid sample”, “contacting the fluid sample”, and “determining an amount of the at least one miRNA in the fluid sample” and also recite the limitation “when the fluid sample comprises a serum sample”, wherein the transitional phrase “comprises” is open-ended thus does not exclude any unrecited fluid samples even in major amounts. See MPEP §2111.03. That is, the instant claims as currently amended are not whatsoever limited to the miRNAs in “serum” only as evidenced by the explicit recitation of determining miRNAs “in the fluid sample”, which does not whatsoever limit the fluid sample to a serum sample but broadly encompasses any and all types of fluid samples, together with the open-ended recitation that the sample “comprises” a serum sample, wherein non-serum samples can be present in major amounts relative to the serum sample as broadly written.
In the instant application, there is no disclosure, either implicit or explicit, that the recited miRNAs are expressed at the recited levels for the recited type of TBI in non-serum fluid samples including but not limited to urine, sweat, tears, CSF, whole blood, and saliva. In fact, as already noted in the last Office action, the instantly recited miR-425-5p is not even downregulated in the non-serum fluid sample, saliva, of a mild TBI (mTBI) subject. In fact, mTBI urine samples were not known to contain an decreased expression level of miR-425-5p as evidenced by Table 59 of van Keuren-Jensen et al. (US 2018/0258483 A1, of record). Furthermore, for the sever TBI (sTBI) that is identified by an increased expression level of miR-335 in the serum sample is not identified by an increased expression level of miR-335 in a CSF sample as evidenced by Maheshwari et al. (US 2018/0216187 A1), who failed to identify miR-335 as a biomarker that is differentially upregulated in CSF samples of severe TBI. See Figures 6-7. See also Redell et al. (Journal of Neurotrauma, 2010, 27:2147-2156, applicant’s citation), who also failed to detect an increased expression level of miR-335 in plasma samples of severe TBI patients. See Figure 2. See also the post-filing Di Pietro et al. reference (Frontiers in Neurology, 2018, 9:429, applicant’s citation) co-authored by the instant co-inventors, which expressly discloses that miRNA biomarkers for the same type of TBI differ for different fluid sample types: plasma, serum, CSF, and saliva. See Table 2. As such, the prior art teachings regarding the fluid sample-dependent differences in miRNA biomarkers remained unchanged even after the filing date sought in the instant application, wherein the post-filing reference co-authored by the instant co-inventors clearly corroborate the position of the examiner in maintaining the instant rejection as the reference reflects the unpredictability and lack or pertinent prior art knowledge pertaining to the genus of “fluid” samples as providing the diagnostic value for the recited miRNAs for the recited types of TBI. Again, in view of the instant specification’s own disclosure that miRNA biomarkers are not the same between two different fluid samples (serum vs. saliva) for mTBI together with the prior art’s teachings of van Keuren-Jensen, Maheshwari, and Redell, further corroborated by the post-filing reference by Di Pietro, one of ordinary skill in the art would not reasonably consider that the instant specification conveys that the instant co-inventors had possession of the claimed diagnostic method wherein the fluid sample “comprises” serum in any amount but does not exclude any other fluid samples including CSF, plasma, urine, and saliva even in major amounts.
In view of the foregoing, this rejection is maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 5, 12-13, 17-22, 28-29, and 32-36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-2, 5, 12-13, 17-22, 28-29, and 32-36 recite the broad recitation of “fluid sample” and also simultaneously recite in the same claims “the fluid sample comprises a serum sample”, which is the narrower recitation of the broad recitation. Hence, it is unclear whether the “fluid sample” recited in multiple lines of claim 1 should comprise a serum sample.
Claims 1-2, 5, 12-13, 17-22, 28-29, and 32-36 now recite identifying/diagnosing specific types of TBI: sTBI, m-sTBI, and mTBI. However, the claims fail to particularly point out which of the recited treatment from “administering a neuroprotective drug, administering a sedative, avoiding hypertensive resuscitation, removing the subject from activity, admitting the subject to hospital, or surgery” should be applied to which of the three different types of TBI. That is, the claims fail to specifically claim which treatment should be administered to which of the three types of TBI patients.
Claims 2 and 5 recite multiple additional miRNAs to be determined in the fluid sample. It is noted that claim 1 as currently amended expressly specifies different types of TBI (sTBI, m-sTBI, mTBI) are associated with different miRNAs. As such, the non-specifically recited miRNAs in claims 2 and 5 fail to particularly point out which miRNAs are useful for identifying which types of TBI.
Claim 13 recites that a subject having the increased expression level of miR-21 “is identified as having severe TBI (sTBI)”. However, claim 12 by virtue of claim dependency from claim 1 necessarily and inherently recites that miR-21 expression level identifies “moderate-severe TBI (m-sTBI)”. Hence, claim 13 recites conflicting limitations (sTBI vs. m-sTBI) pertaining to the patient population identified by miR-21, thereby rendering the claim indefinite.
Claims 17, 22, and 28 recite that the method of claim 1 “further” comprises using “a substrate functionalized with a probe”. It is unclear whether the “probe” recited as an additional, “further” method step is same as or different from the “probe” already required to be used in claim 1.
Claim 18 recites that the “probe” of claim 17 “comprises a nucleic acid.” It is unclear whether the “probe” recited as an additional, “further” method step is same as or different from the “probe comprising a nucleic acid” already required to be used in claim 1.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 5, 12-13, 17-22, 28-29, and 32-36 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-2, 5, 12-13, 17-22, 28-29, and 32-36 now recite identifying/diagnosing specific types of TBI: sTBI, m-sTBI, and mTBI. However, the broadly recited “method of treating traumatic brain injury (TBI)” is not adequately described to provide treatment for each of the specific types of TBI that are now expressly recited in the claims as currently amended. That is, the specification fails to provide adequate written description as to which of the recited “therapies” should be used for which specific type of TBI patients having been identified to have sTBI, m-sTBI, and mTBI.
In addition, claims 32-36 recite “the fluid sample comprises a serum sample”. As amply explained in the last Office action and further elaborated hereinabove in maintaining the §112(a) rejection, both of which are fully incorporated by reference herein thus will not be repeated, there is inadequate written description support for the open-ended fluid sample’s ability to express the recited miRNA in each of claims 32-36.
In view of the foregoing, it is concluded that the instant specification fails to reasonably convey that the instant co-inventors had possession of the genus as now claimed as of the filing date sought in the instant application.
Conclusion
No claim is 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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635