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 preliminary amendment filed on July 14, 2026 is acknowledged. Claims 1-24 have been canceled. Claims 25-41 are pending.
Election/Restrictions
Applicant’s election without traverse of the following species: SEQ ID NO: 54 (V117.26 in Table 13) targeting the SERPINA1 mRNA in the reply filed on July 14, 2026 is acknowledged.
Newly submitted claims 39-41 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Group I, claims 25-38, drawn to a chemically modified oligonucleotide for site-directed A-to-I editing of a target adenosine in a SERPINA1 RNA in a cell with endogenous ADAR.
Group II, claims 39-41, drawn to a method of inducing A-to-I editing of a target adenosine in a subject.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of the chemically modified oligonucleotide of claim 25, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Monian et al. (WO 2021/071858; reference cited by Applicant).
Monian et al. teaches oligonucleotides for editing target adenosine in target nucleic acids to correct a G to A mutation by converting A to I [00156]. Monian et al. teaches that a mutation (i.e., c.1024G>A) in SERPINA1 gene leads to a glutamate to lysine substitution at amino acid position 342 (E342K, "Z mutation") of the mature AIA T protein. This missense mutation affects protein conformation and secretion leading to reduced circulating levels of AIA T. Alleles carrying the Z mutation are identified as PiZ alleles [00836]. Figure 19 (reproduced below) depicts editing of SERPINA1 (PiZ allele) in primary mouse hepatocytes. Compositions all target an adenosine in the mutant human SERPINA1 transcript (PiZZ allele) [0041].
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Monian et al. teaches WV-27820 which is an oligonucleotide that targets SERPINA1:
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[Table 1C, page 220] wherein m is 2’-OMe, f is 2’-F, * is phosphorothioate, I is nucleobase is hypoxanthine, and nucleoside units are unmodified and contain unmodified nucleobases and 2’-deoxy sugars unless otherwise indicated (e.g., with m) [page 241]. WV-27820 is 32 nucleotides in length wherein the central nucleoside of the CBT is a cytidine, at least two of the three nucleosides of the CBT are deoxyribonucleosides, and the nucleoside at the 3’ position of the CBT is a deoxyinosine. In addition, the nucleosides outside of the CBT comprises at least one 2’-OMe modified nucleoside and at least one 2’-F modified nucleoside and all linkages between the nucleosides are phosphorothioate.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 39-41 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 39-41 are withdrawn.
Claims 25-38 are examined on the merits herein.
Priority
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 1, 2024 and July 14, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
The listing of references in the specification is not 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.
Drawings
The drawings were received on November 30, 2023.
The drawings are objected to because 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”. In addition, the figure label for Figures 2 and 4 are not oriented in the same direction as the figure. See 37 CFR 1.84(p)(1).
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.
Specification
The substitute specification filed on June 17, 2024 has been entered.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract uses the phrase “The present invention” which can be implied, the abstract is more than 150 words in length, and the abstract ends with a comma instead of a period. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
Page 7, first line reads in part “not more then 5…not more then 4”. Both instances of “then” should be “than” (emphasis added).
In the description of the figures section, the heading for each figure should include the letter designations and a brief description of each figure must be provided (e.g., Figure 2 should be labeled as Figures 2A through 2E and a brief description must be provided for Figures 2A, 2B, 2C, 2D, and 2E).
Page 11, third paragraph (section for Figure 4) reads in part “preferred GADPH constructs” and should read “GAPDH” (emphasis added).
Page 11, section for Figure 5 reads in part “GADPH-targeting constructs” and should read “GAPDH” (emphasis added).
Page 11, section for Figure 6 reads in part “STAT1 Y701” and should read “Y701C” (emphasis added).
Page 12, heading for Example 1 (see arrow in image below):
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Appropriate correction is required.
Claim Objections
Claims 25, 27, 31, 32, and 33 are objected to because of the following informalities:
Claim 25 recites the abbreviations SERPINA1, ADAR, and A1AT. The abbreviations should be clearly written out at their first occurrence in the claim and should be followed by the abbreviation in parentheses.
Claim 25 recites in part “SERPINA RNA” and should recite “SERPINA1 RNA” (emphasis added).
Claim 25 recites in part “wherein the nucleosides outside of the CBT comprises at least one 2'-O-Methyl (2'-O-Me) modified nucleosides and at least one 2'-fluoro (2'-F) modified nucleosides”. The second and third recitation of “nucleosides” should recite “nucleoside”. In addition, “Methyl” should recite “methyl” (emphasis added).
Claim 27: the first instance of “nucleosides” should recite “nucleoside”.
Claim 31: the second instance of “nucleosides” should recite “nucleoside”.
Claim 32: the second instance of “nucleosides” should recite “nucleoside”.
Claim 33: “nucleosides” should recite “nucleoside”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, and 38 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Monian et al. (WO 2021/071858; reference cited by Applicant).
Regarding claims 25, 26, 27, 28, 29, 30, 34, 37, and 38, Monian et al. teaches oligonucleotides for editing target adenosine in target nucleic acids to correct a G to A mutation by converting A to I [00156]. Monian et al. teaches that a mutation (i.e., c.1024G>A) in SERPINA1 gene leads to a glutamate to lysine substitution at amino acid position 342 (E342K, "Z mutation") of the mature AIA T protein. This missense mutation affects protein conformation and secretion leading to reduced circulating levels of AIA T. Alleles carrying the Z mutation are identified as PiZ alleles [00836]. Figure 19 (reproduced below) depicts editing of SERPINA1 (PiZ allele) in primary mouse hepatocytes. Compositions all target an adenosine in the mutant human SERPINA1 transcript (PiZZ allele) [0041].
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Monian et al. teaches WV-27820 which is an oligonucleotide that targets SERPINA1:
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[Table 1C, page 220] wherein m is 2’-OMe, f is 2’-F, * is phosphorothioate, I is nucleobase is hypoxanthine, and nucleoside units are unmodified and contain unmodified nucleobases and 2’-deoxy sugars unless otherwise indicated (e.g., with m) [page 241]. WV-27820 is 32 nucleotides in length wherein the central nucleoside of the CBT is a cytidine, at least two of the three nucleosides of the CBT are deoxyribonucleosides, and the nucleoside at the 3’ position of the CBT is a deoxyinosine. In addition, the nucleosides outside of the CBT comprises at least one 2’-OMe modified nucleoside and at least one 2’-F modified nucleoside and all linkages between the nucleosides are phosphorothioate. Further, Monian et al. teaches that chirally controlled oligonucleotide compositions provide high levels of adenosine modifying (e.g., converting A to I) activities with various isoforms of an ADAR protein [0015].
Regarding claims 31 and 32, Monian et al. teaches that sugars comprising 2’-OR are consecutive and a first domain comprises 2, 3, 4, 5, or 6 consecutive sugars at its 5’-end, wherein each sugar independently comprises 2’-OR and in some embodiments 2’-OR is 2’-OMe [00487].
Regarding claim 33, Monian et al. teaches that in some embodiments a 2’-modification is 2’-MOE [00116].
Regarding claim 36, Monian et al. teaches that ADAR-recruiting loops are optional and not required [00763].
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 35 is rejected under 35 U.S.C. 103 as being unpatentable over Monian et al. (WO 2021/071858; reference cited by Applicant) as applied to claims 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, and 38 above.
Regarding claim 35, the teachings of Monian et al. are discussed above.
Although Monian et al. does not explicitly teach wherein the oligonucleotide comprises a block of three consecutive 2’-O-Me modified nucleosides at each of the 5’ end and the 3’ end, Monian et al. teaches that sugars comprising 2’-OR are consecutive and a first domain comprises 2, 3, 4, 5, or 6 consecutive sugars at its 5’-end, wherein each sugar independently comprises 2’-OR and in some embodiments 2’-OR is 2’-OMe [00487].
It would have been obvious to try to modify the oligonucleotide wherein the oligonucleotide comprises a block of three consecutive 2’-O-Me modified nucleosides at each of the 5’ end and the 3’ end in the process of optimizing the oligonucleotide because Monian et al. taught that sugars comprising 2’-OR are consecutive wherein each sugar independently comprises 2’-OMe and Monian et al. also taught that there are over 20,000 conditions, disorders or diseases associated with G to A mutation and can benefit from A to I editing [0022].
Conclusion
No claims are allowed.
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
