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 .
This Office Action is in reply to Applicants’ correspondence of 4/24/2026. Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put this application in condition for allowance. New grounds of rejection, necessitated by amendments, are presented in this Office Action. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action. This Action is FINAL.
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Status
Claims 1, 3, 11-12, 14, 23-25, 33, and 41-42 are pending.
Claims 23-25, 33, and 41-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/15/2025.
Claims 1, 3, 11-12, and 14 are being examined on the merits.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted (Figure 1 is in color). Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Response to Remarks
Applicant’s filing of a Petition to Accept Color Drawings is acknowledged. At the time of this action the petition has not been reviewed, and will be decided in a separate correspondence. Until such time that the petition is granted, the drawings will remain objected to. However, please note that if the petition is granted, this objection will be withdrawn.
Specification
The disclosure is objected to because of the following informalities: On page 4, lines 28-30, the specification states that the application contains at least one drawing executed in color. However, no petition to include color drawings has been provided, meaning no drawings will be present in color. If a petition is filed with the Office to include colored drawings, this statement can remain. If no petition is filed, it should be removed.
Appropriate correction is required.
Applicant’s amendment to the specification to properly denote a trade name/mark used in commerce is acknowledged.
Response to Remarks
Applicant’s filing of a Petition to Accept Color Drawings is acknowledged. At the time of this action the petition has not been reviewed, and will be decided in a separate correspondence. Until such time that the petition is granted, the specification will remain objected to. However, please note that if the petition is granted, this objection will be withdrawn.
Withdrawn Claim Rejections - 35 USC § 112a – Scope of Enablement
The rejection of claims 1, 3, and 11-16 under 35 U.S.C. 112(a) is withdrawn in light of Applicant’s amendments to the claims and cancellation of claims 13 and 15-16.
Claim Interpretation
Claim 1 recites the limitation “the subject does not comprise or is heterozygous for an APOE variant nucleic acid molecule comprising the variation….”. For purposes of examination, this is being interpreted to mean that the subject can comprise any other nucleic acid variation in the APOE gene as long as the listed variant is not present or present in a heterozygous form.
Claim 14 recites the limitation “wherein the APOE inhibitor is administered in a standard dosage amount”. Given that “standard” is not defined in the instant specification, “standard” dosage amount is being interpreted as an amount that demonstrates successful inhibition of APOE.
Withdrawn Claim Rejections - 35 USC § 102 and 35 USC § 103
The rejection of claims 1, 3, and 11-16 under 35 U.S.C. 102(a)(2) as being anticipated by Freudenberg (Freudenberg et al., US 2022/0233569 A1, EFD of 1/26/2021; cited on IDS of 8/22/2023), as set forth on pages 7-9 of the Office Action of 1/26/2026, is withdrawn in light of Applicant’s amendments to the claims and cancellation of claims 13 and 15-16.
The rejection of claims 1, 3, 11, and 12 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Butovsky (Butovsky et al., US 2017/0334977 A1), as set forth on page 9 of the Office Action of 1/26/2026 is withdrawn in light of Applicant’s amendments to the claims. The rejection of claims 13-15 under 35 U.S.C. 103 as being unpatentable over Huynh (Huynh et al., Cell Press 2017; cited on IDS of 8/22/2023) in view of Williams (Williams et al., Molecular Neurodegeneration 2020; cited on IDS of 3/26/2025) is withdrawn in light of Applicant’s amendments to the claims and cancellation of claims 13 and 15.
The rejection of claim 16 under 35 U.S.C. 103 as being unpatentable over Huynh (Huynh et al., Cell Press 2017; cited on IDS of 8/22/2023) in view of Williams (Williams et al., Molecular Neurodegeneration 2020; cited on IDS of 3/26/2025) as applied to claims 13-15 above, and further in view of Hoekstra (Hoekstra et al., Arterioscler Thromb Vasc Biol 2021; cited on IDS of 3/26/2025) is withdrawn in light of Applicant’s amendments to the claims and cancellation of claim 16.
New Claim Rejections - 35 USC § 102
Necessitated by Amendments
Claims 1, 3, 11-12, and 14 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Freudenberg (Freudenberg et al., US 2022/0233569 A1, EFD of 1/26/2021; cited on IDS of 8/22/2023).
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Claim 1: Freudenberg teaches a method of increasing longevity and/or inducing healthy aging in a subject by administering an APOE inhibitor to the subject wherein the subject is suffering from one or more age-related diseases (paragraph [0008]). Freudenberg teaches administering the APOE inhibitor to subjects that are APOE reference (reads on wherein the subject does not comprise…an APOE variant nucleic acid molecule; paragraph [0008]). Specifically, Freudenberg teaches that a subject is reference if the subject “does not have a copy of an APOE predicted loss-of-function variant” (paragraph [0023]). According to the specification of the instant application, all listed variants of claim 1 are predicted loss-of-function variants (pg 51, ln 9-10). Freudenberg teaches that the “age-related disease” being treated is “Alzheimer’s disease” (paragraph [0026]). Freudenberg teaches that the subject is a human subject (paragraph [0021]). Freudenberg teaches that the APOE inhibitor is an antisense nucleic acid molecule, siRNA, or shRNA that hybridizes to an APOE mRNA (paragraph [0030]).
Claim 3: Freudenberg teaches that the inhibitor of APOE is an antisense nucleic acid molecule, siRNA, or shRNA that hybridizes to an APOE mRNA (paragraph [0030]).
Claim 11: Freudenberg teaches that the APOE inhibitor is a small molecule, such as a soluble receptor for LDL (LDLR; paragraph [0041]).
Claim 12: Freudenberg teaches that the APOE inhibitor is an antibody (paragraph [0041]).
Claim 14: Freudenberg teaches that a standard dosage amount of an inhibitor is administered to subjects that are APOE reference (i.e., are not heterozygous for an APOE variant; paragraph [0045]).
New Claim Rejections - 35 USC § 103
Necessitated by Amendments
Claim(s) 1, 3, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Huynh (Huynh et al., Cell Press 2017; cited on IDS of 8/22/2023) in view of Cole (Cole et al., WO 2022/066956 A1, EFD of 9/24/2020).
Huynh teaches a method of inhibiting APOE via treatment with an antisense oligonucleotide.
Claims 1 and 3: Huynh teaches that the APOE gene (specifically the APOE-e4 missense variatn) is a genetic risk factor for late-onset Alzheimer disease (AD). Huynh teaches modulating/inhibiting plaque formation and toxicity (treating AD) by administering an APOE inhibitor to the subject (Abstract). Huynh teaches that the inhibitor is administered to subjects that are homozygous for a specific missense variant, human APOE4. While not explicitly stated, the mouse models employed by Hunyh specifically study the APOE4 human variant, with the implication that said model only contains the listed APOE4 variation. Therefore, the subject does not comprise any of the APOE variations listed in claim 1. Huynh teaches that the APOE inhibitor is an antisense oligonucleotide (relevant to claim 1 and claim 3; Abstract).
Hunyh does not teach administering the APOE inhibitor to human subjects. However, administration of APOE inhibitors to human subjects to treat AD is known in the art, as taught by Cole.
Cole teaches administering APOE inhibitors to a subject to treat neurodegenerative disease (such as Alzheimer’s; Abstract and pg 1, ln 10-16).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Hunyh to include administration of the APOE inhibitor to humans, as taught by Cole. One would be motivated to administer this inhibitor to humans given Cole’s assertion that AD is “the most common cause of age-associated dementia” affecting Americans (pg 1, ln 18-20). One would have a reasonable expectation of success given that Cole teaches using antisense APOE inhibitors (similar to the antisense oligonucleotides employed by Hunyh; pg 21, ln 32-33).
Claim 14: Hunyh teaches administering the antisense oligonucleotide APOE inhibitor at an optimal dosage amount for complete inhibition of APOE expression (determined based on age and weight of the mice). Given that the specification does not define “standard” dosage amount, it is being interpreted that the standard dosage is one which successfully inhibits APOE (either through direct interaction or inhibition of expression; see Claim Interpretation above). Therefore, Hunyh teaches administering the APOE inhibitor in a standard dosage amount.
Claim(s) 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Huynh (Huynh et al., Cell Press 2017; cited on IDS of 8/22/2023) in view of Cole (Cole et al., WO 2022/066956 A1, EFD of 9/24/2020) as applied to claims 1, 3, and 14 above, and further in view of Butovsky (Butovsky et al., US 2017/0334977 A1; cited on PTO-892 of 1/26/2026).
The teachings of Huynh in view of Cole are detailed above. Relevant to the instantly rejected claims, Hunyh in view of Cole teach administering an antisense nucleic acid molecule to inhibit APOE to treat Alzheimer’s disease in a subject.
Hunyh in view of Cole do not teach that the APOE inhibitor is a soluble LDLR or an antibody. However, inhibition of APOE through these compounds is known in the art, as taught by Butovsky.
Butovsky teaches treating neurologic diseases by administering an APOE inhibitor (Abstract). Butovsky teaches APOE inhibitors can be a soluble receptor for LDL or an inhibitory antibody (paragraph [0060]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Hunyh in view of Cole to alternately use an inhibitory antibody or a soluble LDLR as taught by Butovsky. One would be motivated to do so given the teaching by Butovsky that these compounds also inhibit the level or activity of APOE in a subject (paragraph [0060]). One would have a reasonable expectation of success given that Butovsky teaches that there is already a recombinant human LDLR (2148-LD/CF) and antibodies for APOE are commercially available or can be generated using “standard methods known in the art” (paragraph [0060 and 0117]).
Response to Remarks
Applicant's arguments filed 4/24/2026 have been fully considered but they are not persuasive for the following reasons. Applicant’s arguments against the rejections laid out in the previous Office Action of 1/26/2026 rely on the new amendments added to claim 1. Said amendments have been addressed in the new grounds of rejection presented above.
Double Patenting
The provisional rejection of claims 1, 3, and 11-16 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 11-12, 14, 16, 23-26, 33, and 41-43 of copending Application No. 17/584,642 (reference application) is withdrawn in light of Applicant’s amendments to the claims and cancellation of claims 13 and 15-16.
Conclusion
No claims are 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 KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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