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 .
Election/Restrictions
This action is in response to the papers filed on 08/25/2026. Claims 1, 4, 7, 9, 11, 14-17, and 19 are currently pending as per claims filed on 04/02/2026.
Applicant’s election with traverse of Group I, which include 1, 4, 7, 9, 11, and 14-16, drawn to an RNA vector, in the reply filed on 08/25/2026 is acknowledged.
Additionally, Applicant’s election with traverse of the following species is acknowledged:
the portion of the intron including the 5' intron end comprises 80% similarity or more to SEO ID NO: 17 or SEO ID NO: 18 (claim 7),
the 5' exon comprises 80% similarity or more to SEO ID NO: 21 or SEO ID
NO: 22 (claim 9) and
the spacer having a sequence comprising 80% similarity or more to SEQ ID NO: 10 (claim 15).
The traversal of the Groups restriction is on the ground(s) that a search of all the claims would not impose a serious burden on the Office and that “Applicants should not be required in the present application to elect a species when applicants have not claimed an unreasonable number of species”.
This argument is not found persuasive because Group I, claims 1, 4, 7, 9, 11, and 14-16, is drawn to an RNA vector; Group II, claim 17, is drawn to a composition comprising a circular RNA; and Group III, claim 19, is drawn to a DNA vector. These groups differ in that they can have materially different applications, contain different compositions, and have materially different structures. They have different classifications and require separate search, and the search would not be coextensive. Thus, inventions I - III are not obvious variants and are patentably distinct from each other. there would be a serious search and/or examination burden if restriction were not required because: a. the inventions have acquired a separate status in the art in view of their different classification; b. the inventions have acquired a separate status in the art due to their recognized divergent subject matter; c. the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries). Applicants’ attention is directed to MPEP 806.05.
In addition, the consideration of the findings of such a search for compliance with the statues and requirements set forth under 35 USC 101,102, 103 and 112 would be unduly burdensome due to the disparate nature and significant breadth of RNA vectors encompassed by the instant claims.
In relation to the species election, the sequences are independent and distinct, each from the other, because they are products which possess characteristic differences in structure and function, and each has an independent utility. The databases that must be searched are large and growing continuously; thus, there is a burden on the Office to search multiple sequences that differ substantially in structure and function. Applicants provide no explanation how a search for "the portion of the intron including the 5' intron end comprises 80% similarity or more to SEO ID NO: 17 or SEO ID NO: 18 “ would also provide an exhaustive search for a "the portion of the intron including the 5' intron end comprises 80% similarity or more to SEO ID NO: 15 or SEO ID NO: 16”. In addition, these species are not obvious variants of each other based on the current record.
Claims 17 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected subject matter, there being no allowable generic or linking claim.
Therefore, claims 1, 4, 7, 9, 11, and 14-16 are subject to examination to which the following grounds of rejection are applicable. The claims are examined as they read on the elected species.
Priority
The instant application is CON of PCT/US2024/049526 filed on 10/02/2024, which claims priority to PRO 63/587,270 filed on 10/02/2023.
Thus, the earliest possible priority for the instant application is 10/02/2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/02/2026 and 08/25/2026 were filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
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 1, 4, 7, 9, 11, and 14-16 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 1 recites at the final two lines “…wherein the permuted group 1 intron/exon is active in the presence of the modified nucleotide.”. It is unclear what the applicant’s intended meaning is for the term, “active” with respect to the “the permuted group 1 intron/exon”. Therefore, the metes and bounds cannot be determined, and the claim is rendered indefinite. It appears the specification describes results that are related to splicing rate and efficiency, circularization efficiency, and ribosome activity. Does applicant intend that “active” mean any of detectable self-splicing, circular RNA production, minimum splicing rate achieved, or a specific circularization efficiency? Applicant must plainly state what they intend to claim.
Claims 4, 7, 9, 11, and 14-16 are rejected as they ultimately depend on and inherit the deficiencies of claim 1.
Claims 7 recites, “…wherein the portion of the intron including the 3' intron end comprises 80% similarity or more to SEQ ID NO: 16 (elected species); and wherein the portion of the intron including the 5' intron end comprises 80% similarity or more to SEQ ID NO: 18 (elected species).”. However, when considering the information provided by the specification with respect to homology, sequence identity, and percent identity, it is unclear what the applicants’ intended meaning for the phrase “comprises 80% similarity or more”. The specification provides the following relevant passages at Pg. 28-29, Paragraphs [120]-[122]:
1. “"Homology" refers to sequence similarity or, interchangeably, sequence identity, between two or more polypeptide sequences or polynucleotide sequences.”
2. “The terms "percent identity" and"% identity," as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm.”
3. “Percent identity may be measured over the length of an entire defined polynucleotide sequence or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence for instance, a fragment of at least 20, at least 30, at least
40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides.”
When considering the claim in light of the relevant descriptions and/or defining passages in the specification, it is unclear whether the recited “80% similarity or more” is determined over the entire length of the instant sequence or unspecified shorter contiguous portions thereof. The specification permits sequence identity to be measured over either the entire sequence or a shorter portion, such that different comparison lengths would produce different determinations as to whether a sequence would fall within the scope of the claim. Therefore, the metes and bounds cannot be determined, and the claim is rendered indefinite.
Claims 9, 11, and 15 are rejected as being indefinite for the same reason as provided in the rejection to instant claim 7 above. As set forth above, the elected sequences of SEQ ID NO: 16 and 18 are indefinite because they recited “80% similarity or more” and it is unclear if the percentage of identity is determined over the entire length of the instant sequence or unspecified shorter contiguous portions thereof. As such the metes and bounds of the claims are indefinite.
Claim Rejections - 35 USC § 112(a)
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.
Claims 7, 9, 11, and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 7, 9, 11, and 15 recite “comprises 80% similarity or more” to a claimed sequence. The instant specification does not describe how to appropriately determine similarity to a given sequence in such a way as to demonstrate that applicant had possession of the instant invention as claimed at the time of filing of the instant application, or as of the effective filing date of the instant application.
The specification is drawn to “circular mRNA platforms for expressing target proteins. Further disclosed herein are circular mRNA platforms for transient gene therapy with reduced immunogenicity and reactogenicity which can be translated in the presence of modified nucleotides (for example, pseudouridine and Nl-methylpseudouridine). Also disclosed herein are the methods and constructs for preparing these nucleoside-modified circular mRNAs.” Pgs. 1-2, Summary, Paragraph [0005]). However, when considering the subject matter with respect to homology, sequence identity, and percent identity, it appears that the applicants’ do not provide sufficient written description for one having ordinary skill in the art to ascertain the meaning for the phrase “comprises 80% similarity or more”. The specification provides the following relevant passages at Pg. 28-29, Paragraphs [120]-[122]:
1. “"Homology" refers to sequence similarity or, interchangeably, sequence identity, between two or more polypeptide sequences or polynucleotide sequences.”
2. “The terms "percent identity" and"% identity," as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm.”
3. “Percent identity may be measured over the length of an entire defined polynucleotide sequence or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence for instance, a fragment of at least 20, at least 30, at least
40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides.”
When considering the claim in light of the relevant descriptions and/or defining passages in the specification, it is unclear whether the recited “80% similarity or more” is determined over the entire length of the instant sequence or unspecified shorter contiguous portions thereof. The specification permits sequence identity to be measured over either the entire sequence or an unlimited shorter portion, such that different comparison lengths would produce different determinations as to whether a sequence would fall within the scope of the claim.
Thus, while the words “percent identity”, “sequence identity”, and “sequence similarity” appear in the specification, the specification does not clearly or specifically provide a description of the subject matter currently claimed in the claims such that it is clear that applicant was in possession of the invention as claimed at the time of filing. The applicant is reminded that “simply describing large genus of compounds is not sufficient to satisfy written description requirement as to particular species or sub-genus” Fujikawa v. Wattanasin, 39 USPQ2d 1895 (CA FC 1996). As such, the limitation in claims 7, 9, 11, and 15 which recites that the sequence “comprises 80% similarity or more” to a claimed sequence appears to represent subject matter without appropriate support by the instant filed specification.
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.
Claim 1, 11 and 14-16 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Anderson et al. US 2023/0050306 A1, IDS filed 04/02/2026; hereafter “Anderson”).
Regarding Claim 1, Anderson teaches a precursor RNA comprising a permuted group I intron/exon arranged with a 3’ intron portion and a 3’ exon portion upstream of a protein coding sequence and a 5’ exon and 5’ intron portion downstream, wherein the coding sequence encodes GLuc (Pg. 13, Paragraph [0173]; Fig 1). See image provided below.
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Anderson further teaches PIE (permutated intron-exon splice site) precursor RNA containing N1-methylpseudoouridine (m1Ψ) and teaches complete substitution with m1Ψ abolishes ribosome activity and partial substitution with m1Ψ reduced splicing efficiency (Pg. 20, Paragraph [0218] and [0219]).
Regarding Claim 11, Anderson teaches the use of an EMCV IRES (SEQ ID NO:36), in the precursor RNA (Figs 17, 18, 20) which has 100% similarity to the instant SEQ ID NO:23 (see below alignment).
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Regarding Claim 14, Anderson teaches the use of spacers in its PIE precursor RNA (Abstract; Fig 2A).
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Regarding Claim 15, Anderson teaches polyA-C spacer sequences with greater than 80% similarity to the sequence of instant claim 15 (see alignment below).
Regarding Claim 16, Anderson teaches its system can produce circular RNA from about 200-10,000 nucleotides, which anticipates the range of instant claim 16 (Pg. 3, Paragraph [0025]; Pg. 4, Paragraph [0045]).
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. (US 202230050306 A1, IDS filed 04/02/2026; hereafter “Anderson”) as applied to claim 1 above in view of Li et al. (WO2023046153A1, IDS filed 04/02/2026; hereafter “Li”).
Anderson teaches the RNA vector of claim 1 as iterated above in the 102 rejection, the contents of which are incorporated herein in their entirety.
Regarding Claim 4, Anderson does not specifically teach that its permuted group I intron/exon comprises a mutation relative to a wild-type Azoarcus group I intron/exon.
Li cures the deficiencies of Anderson as Li teaches an improved circular RNA that has high generation efficiency and reduced immunogenicity (Abstract). Specifically, Li teaches a wild-type Azoarcus Group I intron was modified by changing nucleotides in the stem region of the residual circularizing elements, changing AU base pairing to GC, which increases stem stability and improve circularization efficiency of RNA(Pg. 100, Example 8; Fig 27).
It would have been prima facie obvious to a person having ordinary skill in the art at the time of the instant application filing to modify the PIE RNA vector taught by Anderson, to further contain mutated Azoarcus group I intron/exon as taught by Li. One would have been motivated to incorporate this specific modification as the mutation of the Azoarcus circularizing elements were shown to increase stability and improve circularizing efficiency by Li.
There would have been a reasonable expectation of success in combining these teachings as both Anderson and Li are concerned with Group I intron-mediated self-splicing to generate circular RNA, and Li experimentally demonstrates that the wild-type Azoarcus Group I intron is capable of circularizing RNA and the modification Li teaches would expectedly improve upon the RNA vector of Anderson.
Claims 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. (US 202230050306 A1, IDS filed 04/02/2026; hereafter “Anderson”) as applied to claim 1 above in view of Horhota et al. (US 11,679,120 B2; hereafter “Horhota”).
Please see relevant 112b rejection of claims 7 and 9 above with respect to interpretation of % similarity.
Anderson teaches the RNA vector of claim 1 as iterated above in the 102 rejection, the contents of which are incorporated herein in their entirety.
Regarding Claims 7 and 9, Anderson does not specifically teach “wherein the portion of the intron including the 3' intron end comprises 80% similarity or more to SEQ ID NO: 16 (elected sequence); and wherein the portion of the intron including the 5' intron end comprises 80% similarity or more to SEO ID NO: 18” (elected sequence) for instant claim 7. Anderson does not specifically teach “wherein the portion of the intron including the 3' exon end comprises 80% similarity or more to SEQ ID NO: 20 (elected sequence); and wherein the portion of the intron including the 5' exon end comprises 80% similarity or more to SEO ID NO: 18” (elected sequence) for instant claim 9.
Horhota teaches the use of alternative group I introns for permuted intron-exon-mediated circularization, including an Azoarcus -derived intron (Azop1) and further teaches these introns in circular RNA precursor constructs have successful circularization (Columns 954-955, Example 15; Fig. 12A-12B). Horhota teaches that its 3’ and 5’ group I intron fragments may include adjacent natural exon sequences. Moreover, Horhota teaches nucleotide sequences of Azoarcus/Azop1 intron portions, which can be paired intron portions, including the sequence of SEQ ID NO: 151 and SEQ ID NO: 167 (Columns 901-902, Tables 20 and 21) which have 100% similarity to the instant sequences of SEQ ID NO: 16 and 18, respectively (see alignments
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below).
Horchata teaches “In some embodiments, a 5' intron fragment is a fragment having a sequence listed in Table 20. A construct containing a 5' intron fragment listed in Table 20 will contain a corresponding 3' intron fragment in Table 21 (e.g., both representing fragments with the Azopl intron).” (Column 902, Line 50-55). The paired Azop1 sequences contain exon-derived residues immediately adjacent to the Azoarcus intron portions. Specifically, SEQ ID NO: 151 terminates in AATCCGT and the paired sequence of SEQ ID NO: 167 begins with GCGGACTCAT immediately preceding the Azoarcus intron portion (Columns 901-902, Tables 20 and 21). One of ordinary skill in the art would understand these terminal portions of Horhota’s Azop1 intron-fragment constructs constitute adjacent exon-derived portions rather than portions of the catalytic intron itself. AATCCGT has 100% similarity (apart from uracil/thymine notation) to the corresponding portion of sequence of SEQ ID NO: 19 recited in instant claim 9 and the GCGGACTCAT has 100% similarity (apart from uracil/thymine notation) to the corresponding portion of sequence of SEQ ID NO: 21 recited in instant claim 9.
It would have been obvious to a person having ordinary skill in the art at the time of the instant application’s filing to substitute the Azoarcus-derived group I intron portions (including exon elements) taught by Horhota for the group I intron portions taught in the PIE RNA construct of Anderson because Horhota teaches Azoarcus group I introns as functional alternative self-splicing introns for use in PIE mediated RNA circularization. The substitution of a known alternative group I intron element to perform the same known self-splicing/circularization function would be a simple substitution of one known element for another to obtain predictable results.
One of ordinary skill in the art would have a reasonable expectation of success in combining these teachings because Horhota demonstrates that the disclosed Azoarcus derived intron portions support successful RNA circularization in a PIE RNA precursor construct (Example 15; Fig. 12).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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