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
Status of Application/Amendment/Claims
Applicant's response filed 01/28/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 11/03/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 01/28/2026, claims 1-8, 11 and 13-20 are pending in the application. Claims 18-20 are new claims that are in the scope of the elected invention. Claims 13-17 are withdrawn as being drawn to an elected invention. Applicant has canceled claims 9, 10 and 12.
Claims 1-8, 11 and 18-20 are under examination.
Any rejection not reiterated in this Office Action is hereby withdrawn.
New Claim Rejections – necessitated by claim amendments
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.
Claim 1 is 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 pre-AIA the applicant regards as the invention.
Claim 1 recites "treat a disease of a patient" wherein the claimed method is for treatment of a traumatic brain injury (TBI). It is unclear what disease is being treated because a TBI is a condition resulting from injury to the brain which results in various conditions of the brain as a result. For purposes of applying prior art, treating a disease of a patient diagnosed with TBI is interpreted as treating any resulting condition after a TBI, such as edema for example.
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 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 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:
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.
Claims 1-8, 11 and 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Troy et al. (US Application No. 20150165061 of record cited on IDS mailed 11/03/2025), Tucker, Brian, et al. ("Early brain edema is a predictor of in-hospital mortality in traumatic brain injury." The Journal of emergency medicine 53.1 (2017): 18-29) and Marmarou, Anthony. ("A review of progress in understanding the pathophysiology and treatment of brain edema." Neurosurgical focus 22.5 (2007): 1-10).
Regarding claims 1-3, Troy discloses p75ntr is part of the caspase-9 pathway and siRNA can target p75NTR (0055). Troy teach delivery via intranasal administration (0039). Troy teach the inhibitors can be conjugated to a cell-penetrating peptide (0057) and wherein the cell-penetrating peptide can of be Penetratin 1, transportan, pISI, Tat(48-60), pVEC, MAP, and MTS (0058).
Regarding claims 4, 5 and 6, Troy discloses the inhibitors are administered at a concentration between 1 nM and 1,000 nM, inclusive (0044), and wherein the cell-penetrating peptide is conjugated via a disulfide bond (0058).
Regarding claims 7 and 8, Troy et al. teach p75ntr is part of the caspase-9 pathway and inhibitors of other members of the pathway, such as p75ntr, can prevent apoptosis (0055-0057). Troy et al. teach treatment of a edema associated with traumatic brain injury (TBI) (see 0036). Thus inhibition of p75ntr using siRNA would decrease apoptosis.
Regarding claim 11, Troy discloses the double stranded RNA is further attached to a label selected from the group including an enzymatic label (0056).
Regarding claim 20, Roy teach the composition can be in a nasal spray (0079).
Troy does not teach identifying a subject having a TBI before treating the subject or the method reduces neurological impairment of claims 1, 18 and 19.
Tucker et al. teach traumatic brain injury (TBI) from non-penetrating head injury such as a fall or accident (page 19 last para. and page 21 col. 2) and teach conditions such as edema, hemorrhage, parenchymal bleeding and neurological impairment such as confusion, are associated symptoms of TBI (Table 2).
Tucker et al. teach TBI is one of the leading causes of death and disability worldwide. TBI that is serious enough to result in hospitalization or death is projected to affect 10 million people annually and found brain edema may contribute to secondary injury in traumatic brain injury (TBI) and thus, may be a useful prognostic indicator (see page 18 and abstract). Tucker et al. found that patients with documented brain edema had a rate of mortality that was over 10 and demonstrates that the presence of brain edema on the initial CT scan of TBI patients is an independent prognostic indicator of in-hospital death. Tucker et al. teach considering all TBI patients, the likelihood of death increases eight fold if edema is present and increases nearly five-fold in the subset of patients with mild TBI times that of the entire study population (see page 22 second. Column).
It was known in the art that brain edema resulting from TBI can lead to increased intracranial pressure and brain herniation and therapy must commence as soon as possible to prevent neurological deterioration and death (see page 1 and abstract of Marmarou, Anthony. ("A review of progress in understanding the pathophysiology and treatment of brain edema." Neurosurgical focus 22.5 (2007): 1-10). Marmarou also teach lack of treatment for conditions of TBI despite the understanding and the pathophysiology of brain edema (see conclusion abstract).
It would have been obvious to one or ordinary skill in the art to identify a subject as having TBI and after identifying, use the method of Troy et al. to treat the condition of edema given the results of Tucker et al. Tucker et al. found the increased mortality of TBI patients due to edema and because it was known in the art that the methods of Troy could be used to treat edema in TBI subjects, one of skill in the art would have had a likelihood of success. Because Tucker et al. teach other known conditions were identified after the TBI, such as confusion, and Marmarou teach treatment for brain edema must commence as soon as possible after injury to prevent deterioration and death, it would have been obvious to one of skill in the art that treating edema and ultimately improving mortality would in fact treat other symptoms of TBI such as neurological impairment. Furthermore, KSR states an obvious to try rationale may be proper when the possible options for solving a problem are known, finite, and predictable, with a reasonable expectation of success. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Also, see MPEP § 2143.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Response to Applicant’s Arguments
Applicant argues Troy et al. does not teach treatment of TBI. As stated in the new 103 rejection, the prior art teach edema is a serious symptom of TBI and Troy teach the claimed methods treat edema caused by TBI and it would have been obvious to use these methods to treat TBI. Further, TBI is a condition that results in conditions such as brain edema and therefore treating edema would be considered treating TBI or a disease in the subject, which is interpreted to mean, a condition resulting from TBI as explained in the 112b rejection above. Thus Applicant’s arguments are not persuasive.
Conclusion
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).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at 571-272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636