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 .
Applicants’ reply to the July 30, 2025 Office Action, filed October 24, 2025, is acknowledged. Applicants cancel claims 3-4, amend claims 1-2, 5, and 7-9, and add new claims 11-18. Claims 1-2 and 5-18 are pending in this application.
Any objection or rejection of record in the previous Office Action, mailed July 30, 2025, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments. This action is FINAL.
Election/Restrictions
Newly submitted claims 8 and 10 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 8 is drawn to a method of manufacturing an anellovector, classified in C12N 2750/00051. Claim 10 is drawn to a method of delivering an exogenous vector to a cell, classified in C12N 2750/00071. These claims are classified differently than the originally presented and examined claims to the nucleic acid, which are classified in C12N 15/86.
The method of claim 8 and the nucleic acid construct are related as process of making and product. The nucleic acid construct can be prepared by a fully synthetic protocol.
The method of claim10 and the nucleic acid construct are related as a product and process of using. The nucleic acid construct can be used to prepare an exogenous effector by in vitro methods, such as a rabbit reticulocyte method.
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 Accordingly, claims 8 and 10 are withdrawn from consideration as being directed to a non-elected invention.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.
Information Disclosure Statement
The Information Disclosure Statement filed October 24, 2025 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the Sequence Listing filed December 9, 2022 appears to have 0 sequences.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with
o A statement that identifies the location of all additions, deletions or replacements of sequence information relative to the replaced “Sequence Listing XML” as required by 37 CFR 1.835(b)(3);
o A statement that indicates support for the replacement “Sequence Listing XML” in the application, as filed, as required by 37 CFR 1.835(b)(4); and
o A statement that the replacement “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(b)(5).
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125, inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Objections
Claims 1, 11-12, and 14-16 are objected to because of the following informalities:
At claim 1, line 2, “first” should be deleted from the claim because there is no second Anellovirus genome in either this claim, or any dependent claim.
At claim 1, line 5, “UTR” should be changed to “untranslated region (UTR).”
At claim 11, line 1, “first” should be deleted from the claim because there is no second Anellovirus genome in either this claim, or any dependent claim.
At claim 12, line 1, “first” should be deleted from the claim because there is no second Anellovirus genome in either this claim, or any dependent claim.
At claim 14, line 2, “first” should be deleted from the claim because there is no second Anellovirus genome in either this claim, or any dependent claim.
At claim 15, line 2, “first” should be deleted from the claim because there is no second Anellovirus genome in either this claim, or any dependent claim.
At claim 16, line 2, “first” should be deleted from the claim because there is no second Anellovirus genome in either this claim, or any dependent claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 6 and 13 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 6 recites the nucleic acid construct having a spacer sequence of between 1 and 20 amino acids. However, the claim is directed to a nucleic acid sequence, so it is unclear if the amino acid sequence is encoded by the spacer or if the spacer itself is an amino acid sequence.
At claim 13, line 2, it is not clear what is meant by the phrase “suitable for replication.” Are there any particular characteristics of the backbone region that render it suitable for replication of the DNA construct in a bacterium, mammalian cell, or insect cell?
Claim Rejections - 35 USC § 103
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 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.
Claims 1-2, 7, 9, 11-16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Kahvejian et al. (U.S. Patent Application Publication No. 2020/0123203, published April 23, 2020), applied to claims 1-2 above. This rejection is modified as necessitated by Applicants’ amendments.
Regarding claims 1 and 14, Kahvejian discloses a nucleic acid (e.g., DNA) construct comprising a Anellovirus genome comprising a sequence encoding an exogenous effector (claim 1) Kahvejian discloses that the construct comprises a promoter, a nucleic acid sequence encoding an exogenous effector and a protein binding sequence (claim 1). Kahvejian discloses a sequence having at least 85% sequence identity to the Anellovirus 5' UTR conserved domain (nucleotides 323-393 of the nucleic acid sequence of (Table 11'). Kahvejian discloses a fragment of an Anellovirus genome or thereof, placed in tandem with the first Anellovirus genome, which is interpreted as both the Anellovirus genome and the fragment of the Anellovirus genome are on the same nucleic acid construct (Claim 33). Kahvejian discloses that the nucleic acid can also include a GC-rich region (paragraphs [0670]-[0672]).
Regarding claims 2 and 14, Kahvejian discloses that the second Anellovirus genome or fragment thereof has a length of less than 2800, 2700, 2600, 2500, 2000, 1500, 1000, 900, 800, 700, 600, or 500 nucleotides (paragraph (0110]).
Regarding claims 5-6 and 17, Kahvejian that the Anellovirus genome can include membrane penetrating polypeptides, which include linkers (i.e., spacers) that can be 2-30 amino acids long (paragraphs [0513]-[0514]).
Regarding claims 7 and 18, Kahvejian discloses a circular construct having a coding region and non-coding region without a spacer (Figure 2).
Regarding claim 9, Kahvejian discloses a cell comprising the nucleic acid construct (paragraphs [0598]-[0604]).
Regarding claim 11, Kahvejian discloses that the genome comprises a sequence having at least 75% identity with LY2 (claim 1 and paragraphs [0413] and [0670]-[0672]).
Regarding claim 12, Kahvejian discloses that the genome comprises a sequence having at least 75% identity with LY2 (claim 1 and paragraphs [0414] and [0670]-[0672]).
Regarding claim 13, Kahvejian discloses that replication signals can provide for amplification and packaging, which is interpreted as inclusion of a backbone region that is suitable for replication of the DNA in a bacterial cell, a mammalian cell, or an insect cell (paragraphs [0553], [0654]-0659] and [0680]-[0685] and Example 15).
Kahvejian fails to disclose that the 5’ UTR is situated 3’ of the Anellovirus genome or that the GC-rich region is 5’ of the Anellovirus genome. Kahvejian fails to disclose or suggest that the spacer is between the first Anellovirus genome and the fragment of an Anellovirus genome.
However, Kahvejian discloses expression of multiple DNA sequences attached in tandem (paragraph [0443]. Kahvejian discloses that one promoter element can increase an amount of products expressed for multiple DNA sequences attached in tandem (paragraph [0443]).
Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the single promoter element of Kahvejian can enhance the expression of one or more products, which is interpreted either fragment of Anellovirus genome (the 5’ UTR or the GC-rich region) could be positioned either 3' or 5' relative to the first Anellovirus genome according to how expression is desired to be controlled. One of ordinary skill in the art would have been motivated to alter the order of the fragments and the Anellovirus genome in order to provide reproducible control of expression of the exogenous effector.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to determine an optimal location for a spacer sequence, which provides for transporting components across a cell membrane. One of ordinary skill in the art would have been motivated to place the linker between the Anellovirus genome and the fragment of an Anellovirus genome in order to ensure the vector crosses into the cell via the membrane penetrating polypeptide and to provide for efficient transcription and translation of the exogenous effector.
Response to Amendments and Arguments
Regarding the Sequence Listing, Applicants are correct in noting that ST.25 is the applicable Sequence Listing rules. However, the Sequence Listing submitted December 9, 2022 appears to be devoid of any sequences. Thus, a new Sequence Listing should be submitted and all requirements listed above should be met.
Regarding the rejection under 35 U.S.C. §§ 102(a)(1) and 102(a)(2), Applicants’ arguments have been fully considered and are deemed to be persuasive. Therefore, this rejection is withdrawn.
Regarding the rejection under 35 U.S.C. §§ 103, Applicants’ arguments have been fully considered but are not deemed to be persuasive.
Applicants assert that Kahvejian does not teach or suggest a single nucleic acid construct as required by amended claims 1. Applicants assert that Kahvejian does not teach or suggest that the nucleic acid construct includes both a first Anellovirus genome and a fragment of a second Anellovirus genome. Applicants assert that the instant nucleic acid construct comprising a GC-rich region positioned 5’ to a full Anellovirus genome.
To begin, Kahvejian does teach a single nucleic acid construct that includes a sequence encoding an exogenous effector, along with a promoter, a nucleic acid sequence encoding an exogenous effector and a protein binding sequence, as discussed above. Kahvejian an Anellovirus 5' UTR conserved domain and a GC-rich region. Because Kahvejian discloses a fragment of an Anellovirus genome or thereof, placed in tandem with the first Anellovirus genome, the reference is interpreted as both the Anellovirus genome and the fragment of the Anellovirus genome are on the same nucleic acid construct.
Applicants assertion of a first and second Anellovirus genome (or fragment) recites limitations that are not in independent claim 1 or claim 14, nor in any of the dependent claims. The term “second Anellovirus genome” is not a limitation in any claim. And it is improper to import claim limitations from the specification. "Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment." Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
And because Kahvejian clearly discloses Anellovirus genomes with both a 5’ UTR and a GC-rich region, it would have been at least obvious to try different ordering of the nucleic acid constructs in order to provide a construct that, when introduced into a cell, is able to express the exogenous effector in a desired amount in order to provide therapeutic benefits. Because the number of claimed components of the nucleic acid construct is finite and limited, one of ordinary skill in the art would have found the ordering of the Anellovirus genome components obvious to try to obtain the desired exogenous effector expression results. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).
For all these reasons, and those listed above, Kahvejian is deemed to render the claims 1-2, 7, 9, 11-16, and 18 obvious.
Conclusion
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 NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, NEIL HAMMELL can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636