DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22 June 2026 has been entered.
Response
No amendments have been made to the claims since 10 November 2022. Claims 1-55 were previously cancelled and claims 56-63 are pending in the instant application and are under examination in the instant office action.
No new grounds for rejection are presented in this Office action. Rather, the Examiner has provided all the same claim mapping presented in the Non-Final action mailed 15 February 2024, along with the same response to Applicant’s identical, verbatim arguments from previous Final rejections together in this single action, so that one need not review multiple actions within the file wrapper.
Information Disclosure Statement (Maintained)
Listing of references in the specification does not constitute 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, they have not been considered. Specifically, no IDS has been filed to remedy the deficiencies between those references cited in the specification (ex. “Masliah et al., 1991” on page 3 and “Noguchi et al., (2009)” on pages 19 and 57; etc.) and those that appear on the proper information disclosure statement filed on 15 February 2023. Applicant is reminded of the duty to disclose information material to patentability under 37 C.F.R. 1.56.
Priority
As indicated in the Non-Final office action dated 02/15/2024, Claim 56 has an effective filing date of 22 February 2010, and claims 57-63 have an effective filing date of 22 February 2011.
Applicant has not traversed these effective filing dates or priority claim.
Claim Rejections - 35 USC § 102 (Maintained)
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 pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
Claim 56 stands as rejected under pre-AIA 35 U.S.C. 102(a)(1) as being anticipated by Knauer et al., PNAS, 89:7437-7441, 1992 for reasons of record in the previous action.
On pages 2-3 of Remarks filed 22 June 2026, Applicant traverses the rejection on the grounds. Applicant states Claim 56 is drawn to a composition of matter comprising (i) cultured human skin fibroblast cells in contact with (ii) Aß peptide. This composition permits performing certain PKC epsilon protein-based methods described in the application for diagnosing Alzheimer's disease in a human patient. Applicants maintains that the Examiner has not shown how Knauer teaches every element of the claimed composition. Claims 57, 58, 61, and 62 provide a composition of matter comprising (i) cultured human skin fibroblast cells in contact with (ii) amylospheroids (ASPDs). This composition permits performing certain PKC epsilon protein-based methods described in the application for diagnosing every AD.
These are verbatim the same arguments presented in the previous Remarks. It should be noted that Applicant's arguments also fail to comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art as disclosed by the references cited.
As previously stated, Applicant appears to be asserting that the composition of the claims “permits performing” a diagnostic method. This, however, is merely intended use, that imposes no material/structural limitation upon the elements of the claim (See MPEP 2111.02(I) and (II)). Applicant has failed to point out how the composition of the claims differs from the composition disclosed in Knauer.
Regarding claim 56, Knauer et al. teaches synthesis of labelled peptides of amyloid β1-28, β1-39, and β1-42 (pg. 7437, Materials, first sentence) and confluent human skin fibroblasts (Abstract; pg.7438, Cell culture, first sentence) in contact with each other (pg. 7438, Uptake/Degradation, first sentence). The instant specification equates these amyloid beta oligomers that are highly toxic with “amylospheroids” from AD patient brains (paragraph [00103]). Therefore, the prior art anticipates a composition of matter comprising cultured human skin fibroblasts in contact with Aβ peptide, as claimed.
Applicant has presented no evidence of structural difference between the composition of the claims and that of the prior art
MPEP 2112.01(II) states: “Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
The burden of proof is upon the Applicant to show a novel or unobvious distinction between the structural characteristics of prior art composition and those of the claimed composition. Patent owner’s burden under the circumstances presented herein was described in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977) as follows:
Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . .
Therefore, the rejection is maintained.
Claims 57-58 and 61-62 stand as rejected under pre-AIA 35 U.S.C. 102(a)(1) as being anticipated by Cecchi et al., Neurobiology of Aging, 28:863-876 (2007) for reasons of record in the previous action.
On pages 2-3 of Remarks filed 22 June 2026, Applicant traverses this rejection by stating: “This composition permits performing certain PKC epsilon protein-based methods described in the application for diagnosing Alzheimer’s disease in a human patient. Applicants again respectfully maintain that the Examiner has not shown how Cecchi teaches every element of the claimed composition.”
This argument does not comply with 37 CFR 1.111(c) because it does not clearly point out the errors in the rejection nor point out the patentable novelty which Applicant thinks the claims present in view of the prior art.
Regarding the composition of Claim 57, the Cecchi prior art teaches cultured human skin fibroblast cells from controls and patients belonging to Familial Alzheimer’s Disease cohorts (pg. 865, at section 2.4) in contact with amylospheroids (ASPDs) (pg. 868 at 3.2 and Fig. 5). This anticipates the “composition of matter comprising (i) cultured human skin fibroblast cells in contact with (ii) amylospheroids (ASPDs)” of instant claim 57.
Regarding Claims 58 and 63, the instant specification teaches [00173] Preparation of soluble oligomeric Aβ: Oligomeric Aβ was prepared following the method described by Noguchi et al., (2009). The specification teaches Aβ generated by this method was reported to be highly neurotoxic, 10-15nm spherical Aβ assemblies termed as amylospheroids (ASPDs). Paragraph [00103] defines these same 10-15nm amylospheroids as being >100kDa. Cecchi et al. teach the ASPDs comprise Aβ 1-42, wherein it teaches “Aβ 1-42 prefibrillar aggregates” (pg. 865, first paragraph) were contacted with healthy and FAD fibroblasts for differing times (0, 10, 20, 30, 60 min) with 1.0µM Aβ aggregates” (pg. 865, at bullet 2.5). Therefore, the prior art teaches compositions wherein the ASPDs comprise Aβ 1-42 of instant claim 58 and 63.
Regarding Claims 59 and 63, Cecchi et al. teach the globules display a tendency to self-assemble (pg. 868, first paragraph). Figure 1D of the reference teaches a z range (the z axis, indicating 3 dimensional size) of 25 nm (figure legend). Cecchi et al. teach, after 48 h of incubation, larger globular assemblies (10–15 nm high) are observed (Fig. 1D). Thus, since Cecchi discloses these globular assemblies to be these same 10-15 nm high and 25nm on the z axis, then these equate to the 10-15nm amylospheroids of the instant specification that are disclosed as being >100kDa. Thus, Cecchi anticipates compositions wherein the ASPDs have a molecular weight of greater than 100 kDa, as required by instant claims 59 and 63.
Regarding claims 60 and 63, Cecchi et al. teaches incubating fibroblasts with varying concentrations over the range of 1nM to 10 µM of Aβ 1-40 aggregates or Aβ 1-42 assemblies. This teaches concentrations covering a range that includes 500 nM, of instant claims 60 and 63.
Regarding claims 61 and 63, Cecchi et al. teaches human skin fibroblast cells cultured to confluence (pg. 865, at bullet 2.4) as recited by instant claims 61 and 63.
Regarding claims 62 and 63, Cecchi et al. teach fibroblasts were cultured at 37 ◦C in culture medium and contact with the amylospheroids occurred at 37 ◦C, therefore the prior art teaches compositions comprising the amylospheroids and cultured human skin fibroblast cells from healthy and FAD patients wherein the temperature of the composition is 37 C, as required by instant claims 62 and 63.
Applicant has failed to provide any evidence that the structure disclosed in Cecchi materially differs from the claimed composition.
Therefore, the rejection is maintained.
Claim Rejections - 35 USC § 103 (Maintained)
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 59-60 and 63 stand as rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Cecchi, applied to claims 57-58 and 61-62 above, and further in view of Hoshi et al., 2003 for reasons of record in the previous action.
On pg. 3 of Remarks (Id), Applicant traverses this rejection on the grounds: “the ASPDs have a molecular weight of greater than 100 kDa (claim 59), the ASPD concentration is 500 nM (claim 60), or (i) the ASPDs comprise Aβ1-42, have a molecular weight of greater than 100 kDa, and have a concentration of 500 nM; (ii) the cultured human skin fibroblast cells are confluent; and (iii) the temperature of the composition is 37° C (claim 63). These compositions permit performing certain PKC epsilon protein-based methods described in the application for diagnosing Alzheimer's disease in a human patient. Which are the verbatim arguments previously presented in Remarks filed 15 August 2024 and addressed in every rejection since the Final action mailed 11/21/2024.
These arguments are unpersuasive because, first, permitting performing a method for diagnosis is an unclaimed feature; and, second, a recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. No structural difference has been pointed out by Applicant even though the burden of proof is upon the Applicants to show a novel or unobvious distinction between the structural characteristics of prior art composition and those of the claimed composition. MPEP 2112.01(II) states: “if the composition is physically the same, it must have the same properties.” The instant application cites the ASPD of Hoshi are “>100kDa” (see citation of Hoshi et al. 2003 at paragraph [00103] of the instant specification).
For all these reasons, the rejection is maintained.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(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 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 STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
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