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
Applicant's amendments and remarks filed on December 15, 2025 are acknowledged. Claims 1-5, 7-8, and 10-13 have been canceled. Claims 6 and 9 were amended. Claims 6, 9, and 14 are pending.
It is noted that the amendment to the claims filed on December 15, 2025 does not comply with the requirements of 37 CFR 1.121(c) because the claims do not reflect the immediate prior version. Specifically, the last line of claim 9 filed on December 15, 2025 recites in part “
This action is NON-FINAL due to new grounds of rejection not necessitated by amendment.
Election/Restrictions
Applicant’s election of Group III (claims 6-7 in full and claim 9 in part) in the reply filed on June 6, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Newly added claim 14 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 6 and 9 are examined on the merits herein.
Priority
This application claims priority to PCT/CN2019/096755 filed on July 19, 2019.
Withdrawn Objections
In view of Applicant’s amendments and response, the objection to the drawings in reference to the view numbers is withdrawn.
In view of Applicant’s amendments and response, the objections to the specification are withdrawn.
In view of Applicant’s amendments and response, the objection to claims 6 and 9 is withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 101, 35 U.S.C 112(b), and 35 U.S.C 102 rejections are withdrawn.
Drawings
The drawings were received on December 15, 2025.
The drawings are also objected to because Figures 2E, 6C, 6D, and 7A are blurry and difficult to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Response to Arguments
Applicant's arguments filed December 15, 2025 have been fully considered but they are not persuasive.
Applicant asserts that the drawings have been amended to obviate the objections; however, Figures 2E, 6C, 6D, and 7A are still blurry and difficult to read.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See page 38.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figure 5.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Response to Arguments
Applicant's arguments filed December 15, 2025 have been fully considered but they are not persuasive.
Applicant asserts that the original specification and drawings contain 94 sequences wherein 65 of the sequences are identified by a SEQ ID NO. and the remaining 29 sequences lack a SEQ ID NO. Applicant further asserts that the specification and drawings have been amended to assign a SEQ ID NO. to each of the remaining 29 sequences. However, page 38 of the specification filed on December 15, 2025 still contains a sequence without a SEQ ID NO. (see below). In addition, FIG. 5 still contains sequences that are not identified by a SEQ ID NO.
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Specification
The substitute specification filed on December 15, 2025 has been entered.
Claim Objections
Claim 6 is objected to because of the following informality:
To improve the grammar of the claim, the word “and” should be added between the last two wherein clauses of claim 6. Therefore, claim 6 should read in part “SEQ ID NOS: 1-17; and wherein the antisense oligonucleotide” (emphasis added).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 9 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a pharmaceutical composition for treating Alzheimer’s disease comprising a circAβ inhibitor according to claim 6 and a pharmaceutically acceptable carrier, does not reasonably provide enablement for a pharmaceutical composition for preventing Alzheimer’s disease comprising a circAβ inhibitor according to claim 6 and a pharmaceutically acceptable carrier. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue". These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims and nature of the invention:
Claim 9 is drawn to a pharmaceutical composition for preventing or treating Alzheimer’s disease comprising a circAβ inhibitor according to claim 6 and a pharmaceutically acceptable carrier. The broadest reasonable interpretation of claim 9 is that the pharmaceutical composition encompasses not only treating Alzheimer’s disease comprising a circAβ inhibitor according to claim 6 but also preventing Alzheimer’s disease comprising a circAβ inhibitor according to claim 6.
State of the prior art, level of predictability in the art, and level of one of ordinary skill:
Graham et al. (Annual Review of Medicine 2017) discloses that Alzheimer’s disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology [abstract].
Galvin discloses that ongoing pharmacological trials using anti-amyloid therapies are underway in sporadic and genetic forms of AD, although a large number of modifiable risk factors for AD have been identified in observational studies, many of which do not appear to exert effects through amyloid or tau. Thus suggesting that prevention studies focusing on risk reduction and lifestyle modification may offer additional benefits [abstract]. Galvin further discloses that an important question is whether AD can be prevented and identified a number of modifiable (e.g., exposures, lifestyle and social habits) and nonmodifiable (e.g., age, sex, genetics) risk factors [page 2128, right column]. A number of prevention studies are ongoing in sporadic and autosomal-dominant forms of AD; however, the results are still pending. Nonetheless, the results from the trials may not be generalizable [page 2129, left column, last paragraph bridging to right column, first paragraph]. Furthermore, Galvin discloses that up to 30% of AD cases may be preventable through modification of risk factors and behavioral changes to mitigate the effect of those risk factors that are not modifiable. A prevention initiative needs to be multimodal and tailored to address individual risks [page 2130, left column, last full paragraph].
Amount of direction provided by the inventor and existence of working examples:
The instant specification envisions a pharmaceutical composition for preventing or treating Alzheimer's disease comprising the cyclic ribonucleic acid inhibitor and/or circAβ specific peptide inhibitor and/or Aβ related peptide inhibitor and optionally a pharmaceutically acceptable carrier [page 23, last paragraph].
The instant specification discloses that the circular ribonucleic acid inhibitor comprises the antisense oligonucleotide. Preferably, the cyclic ribonucleic acid inhibitor comprises an oligonucleotide having a sequence selected from SEQ ID NOS: 41-57, or a sequence substantially homologous to these sequences. In certain embodiments, the circular ribonucleic acid inhibitor comprises the inhibitory circular ribonucleic acid [page 24, first full paragraph].
Working example 3 discloses that the specific antisense oligonucleotide against β-amyloid cyclic ribonucleic acid (circAβ) is used to inhibit and degrade circAβ to prevent and treat Alzheimer’s disease. Figures 7A-7C shows that the level of the circular RNA in the cell is reduced by antisense oligonucleotides (anti-circAβ-a-ASO) against β-amyloid cyclic ribonucleic acid-a. Specifically, SEQ ID NO: 41 is shown in Figure 7A (reproduced below).
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Further, the specification discloses that antisense oligonucleotides that bind target RNA can degrade target RNA by activating RNAse H enzyme activity and regulate protein translation.
However, the specification does not provide any working examples of a pharmaceutical composition for preventing Alzheimer’s disease comprising a circAβ inhibitor according to claim 6.
Quantity of experimentation:
In view of the breadth of the claims which embrace a pharmaceutical composition for treating Alzheimer’s disease comprising a circAβ inhibitor according to claim 6 and a pharmaceutical composition for preventing Alzheimer’s disease comprising a circAβ inhibitor according to claim 6, the state and level of predictability in the art, the lack of working examples to show preventing Alzheimer’s disease comprising a circAβ inhibitor according to claim 6, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637