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 . 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.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 15 Sept, 2025 has been entered.
Claims Status
Claims 14-17, 20, and 21 are pending.
Claim 14 has been amended.
Withdrawn Rejections
The rejection of claims 14-17, 20, and 21 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to the addition of new matter is hereby withdrawn due to amendment.
Maintained/Modified Rejections
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.
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) 14-17, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Di Fede et al (Sci Rep. (2016) e:20949, cited by applicants) in view of Erdo et al (Brain Bull. Res. (2018) 143 p155-170) and Le Tourneau et al (J. Natl. Canc. Inst. (2009) 101 p708-720).
Di Fede et al discuss treating Alzheimer’s disease with A2V variants of amyloidβ (title). The therapeutic is Aβ1-6A2V(D); the (D) signifies d-amino acids to increase its stability in vivo; this hinders AβWT oligomer production and amyloid fibril formation (p5, 2nd paragraph). The peptide is non-toxic to cells even at high concentrations (20 µM) and protects cells against WT amyloid (p5, 8th paragraph). This material was conjugated to TAT to make translocation across the BBB possible (p9, 9th paragraph). The conjugated material reduced AβWT production and aggregation, and prevented amyloid deposition with once weekly treatment in a mouse model of Alzheimer’s disease (p7, 9th paragraph).
The difference between this reference and the instant claims is that this reference does not discuss intranasal administration, nor does it discuss dose and dose schedule for the drug.
Erdo et al discuss intranasal administration for brain targeting of drugs (title). This allows for direct access to the brain, bypassing the BBB, and results in beneficial PK/PD profile (p155, 2nd column, 1st paragraph). A handful of studies using this form of administration to direct peptides to the brain to treat animal models of Alzheimer’s disease are mentioned (table 3, p161, table 4, p162, top of page). Various administration forms, including direct application with a cannula, pipette or syringe, a spray, or an atomizer are mentioned (table 1, p158, bottom of page).
Le Tourneau et al discuss dose escalation methods (title). The main goal of a phase I clinical trial is to establish the dose and dose schedule for new drugs or combinations of drugs (abstract). The point of this is to have as many patients as possible in the therapeutic dose range, while preserving safety and maintaining rapid accrual (p708, 1st column, 2nd paragraph). If toxicity is not a limiting factor, the occurrence of drug related biological effects can be used as an endpoint (p708, 2nd column, 1st paragraph). A number of different protocols are mentioned for optimizing these parameters (fig 2, p711, top of page). This reference discusses optimizing the dose and dose schedule.
Therefore, it would be obvious to use the peptide of Di Fede et al (without the TAT) as a substitution of one known element (the TAT of Di Fede et al) with another (the intranasal administration of Erdo et al) yielding expected results (administration to the brain). As the method of Erdo et al is well known for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to optimize the dose and dose schedule of the drug of Di Fede et al, to have as many patients as possible in the therapeutic dose range while preserving safety and maintaining rapid accrual, as discussed by Le Tourneau et al. As all drugs need to have their dose and dose schedule optimized before use in the general public, an artisan in this field will have experience in such optimizations, leading to a reasonable expectation of success.
As Erdo et al provides an alternative method to gain access across the BBB, the TAT is optional in this administration scheme. Di Fede et al discuss using Aβ1-6A2V(D) to treat Alzheimer’s disease if it can cross the BBB. Erdo et al teaches using intranasal administration to cross the BBB, rendering that route of administration obvious. Le Tourneau et al discuss optimizing the dose and dose schedule of the therapeutic. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). Thus, the combination of references renders obvious claims 14, 17, and 20.
This is the same peptide used to treat the same disease as Di Fede et al, so it will necessarily have the same effects, rendering obvious claims 15, 16, and 21.
response to applicant’s arguments
Applicants argue that the sequence of Di Fede et al is conjugated to TAT, which is excluded by “consisting of” language, is silent as to intranasal administration, and the rejection does not avoid a carrier attached to the sequence.
Applicant's arguments filed 15 Sept, 2025 have been fully considered but they are not persuasive.
Applicants argue that the sequence of Di Fede et al is conjugated to TAT. That is an oversimplification. The reference clearly states that the active sequence is Aβ1-6A2V(D), and uses that sequence in in vitro testing. The purpose of the TAT is clearly stated as enabling the sequence to cross the BBB, which, in the logic of the rejection, is unnecessary with intranasal administration.
Applicants argue that Di Fede et al is silent as to intranasal administration. While correct, this deficiency is made up by Erdo et al.
Applicants argue that the rejection leaves a carrier (i.e. TAT) attached to the sequence. That is incorrect. The prior art makes it clear that the purpose of the TAT is the same as the purpose of using intranasal administration. A person of skill in the art would be expected to realize that only one of the two (TAT or intranasal administration) is needed, as they both do the same thing. Applicants argument assumes that a person of skill in the art will automatically follow exactly the same procedure as the prior art states, but the standard is that such an individual has ordinary creativity, not an automaton (MPEP 2141.03(I)).
New Rejections
Claim Rejections - 35 USC § 112(b)
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 14-17, 20, and 21 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.
Claim 14 requires the only active ingredient to be Aβ1-6A2V(D), and that non-active ingredients are compatible with contact with intranasal mucosa. There are two issues with this. Applicants have not defined what an active ingredient is. There are medicinal formulations that use water as an active ingredient (McKession Eye Wash solution, https://www.bettymills.com/mckesson-eye-wash-solution-active-ingredient-983-percent-purified-water-inactive-ingredients-boric-acid-sodium-borate-sodium-chloride-1-oz-squeeze-bottle-144-cs-mck19828-mon1188884cs?srsltid=AfmBOoqcw8aPOh79ikQ6rrsplbyIaFFWf_-Ot9U9h_ji0yhPBO-ZSXq7, downloaded 18 Nov, 2025). Humble (Arizona dept. health services blog post of 19 June, 2012) states that all chemicals are toxic if the dose is high enough (first paragraph). This means that all chemicals will have a therapeutic effect (which may be undesirable). This makes it unclear what applicants consider an active ingredient, and what the limitation of the peptide being the sole active ingredient excludes.
Applicants have also not defined what compatible with contact with intranasal mucosa means. As noted before, all chemicals are toxic with a high enough dose. This could mean anything from “does not usually melt user’s nose if used judiciously” to “harmless in the usual doses to almost all of the population.” Without a definition of the phrase, it is not clear what this limitation excludes.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658