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
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/03/2026 has been entered.
Status of Application/Amendment/Claims
Applicant's response filed 06/03/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 03/09/2026 are hereby withdrawn.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 06/03/2026, claims 1-8, 11, 13-17, 19 and 20 are pending in the application. Claims 13-17 are withdrawn as being drawn to an elected invention. Applicant has canceled claims 9, 10, 12 and 18.
Claims 1-8, 11 and 19-20 are under examination.
Any rejection not reiterated in this Office Action is hereby withdrawn.
New Claim Rejections
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 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alder, Janet, et al. ("Genetic and pharmacological intervention of the p75NTR pathway alters morphological and behavioural recovery following traumatic brain injury in mice." Brain injury 30.1 (2016): 48-65), Troy et al. (US Application No. 20150165061 of record cited on IDS mailed 11/03/2025), Weiss et al. (2010 Recognizing and exploiting differences between RNAi and small molecule Inhibitors [Author Manuscript available in PMC]. Published in final form as Nat. Chem Biol. 3[12]:739-744;) and Marmarou, Anthony. ("A review of progress in understanding the pathophysiology and treatment of brain edema." Neurosurgical focus 22.5 (2007): 1-10 of record cited on 892 mailed 03/09/2026).
Regarding claims 1 and 19, Alder teach traumatic brain injury (TBI) is an alternation in brain function, or other evidence of brain pathology, caused by an external force (i.e. a physical blow to the head) and teach the pro-neurotrophin/p75NTR pathway is induced more than the mature neurotrophin/Trk pathway and that interfering with p75 signaling improves recovery following TBI (see page 1). Alder teach their findings indicate that intervention with p75 signaling reduces apoptosis, neuronal degeneration and astrocytosis and improves outcome on two major objective measures of neurological function following injury: the Morris Water Maze (MWM) and Rotarod test to examine spatial learning and sensorimotor function, respectively (see page 4). Alder et al. teach using a p75 antagonist TAT-Pep5 in a mouse model of brain injury (page 5-6) and found that sensorimotor function can be improved after injury in mice in which p75 signaling is inhibited (see pages 20-21). Alder does not teach using a siRNA inhibitor of p75NTR.
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 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). 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).
It would have been obvious to one of ordinary skill in the art to try using a siRNA to inhibit p75ntr given it was taught in the art that siRNAs are more target-specific than small molecules. Weiss teaches using siRNAs is more target-specific than small molecules and that it is common in the art to use siRNAs and small molecules interchangeably in order to validate one or the other and to determine whether the effects of inhibiting a protein itself (with a small molecule) are different from effects of inhibiting protein expression (with an siRNA) (introduction para 2). Given Troy et al. demonstrates efficient inhibition using siRNA, it would have been obvious to try in methods of treatment of sensorimotor control loss associated with TBI. 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. Further, given Weiss et al. teach siRNA are more target specific than small molecules, there is an expectation of an advantage for their use and thus a motivation to combine the prior art references for use with any type of oligonucleotide (see MPEP 2144).
MPEP 2144:
THE EXPECTATION OF SOME ADVANTAGE IS THE STRONGEST RATIONALE FOR COMBINING REFERENCES
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). See also Dystar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick, 464 F.3d 1356, 1368, 80 USPQ2d 1641, 1651 (Fed. Cir. 2006) ("Indeed, we have repeatedly held that an implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the ‘improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal—and even common-sensical—we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves.").(emphasis added).
Troy does not teach identifying a subject having a TBI before treating the subject.
Regarding the limitation of claim in of ‘identifying a subject having a traumatic brain injury” it was known in the art that certain conditions 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 a TBI and after identifying, use the method of Troy et al. to treat the condition given Mamarou et al. provides teachings of an advantage to identify subjects with a TBI for treatment.
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’s response is acknowledged but not found persuasive. Applicant argues brain edema is distinct from TBI as Marmarou et al. states "edema is an abnormal accumulation of fluid within the brain parenchyma" and TBI is defined in the specification as "clinically detectable brain dysfunction commonly caused by a physical blow to the head area."
In response, Marmarou, Anthony. (cited on 892 mailed 06/03/2026) while discussing edema as a result of a TBI, makes it obvious to identify subjects with a TBI early given conditions develop rapidly with this injury and it would be advantageous to administer any treatment after a TBI.
Applicant’s argument against Tucker et al. will not be addressed as this reference is not used in the new rejection herein.
Applicant argues Troy et all does not discuss treatments for TBI or a decrease of loss of sensorimotor control. As stated in the new 103 rejection, the combination of references makes it obvious to use the siRNA of Troy et al. targeted to p75NTR for treatment of sensorimotor control associated with a TBI and decreasing apoptosis in a patient’s brain.
Conclusion
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 between M-F 8:00am-4:30pm.
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
Prosecution Insights