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 .
Status of the Claims
Claims 1-4, 7, 15-19, 33-35, 52, 65, 97, 106, 109, 113, and 132 are pending.
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 1-4, 7, 15-19, 33-35, 52, 65, 97, 109, and 132 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Stewart et al. (US20200306286A1) as evidenced by NEB (SplintR Ligase, retrieved from internet 07/01/2026) and Vector Builder (retrieved from internet Vector Builder 07/01/2026).
In regards to claim 1, Stewart discloses a circular RNA comprising, in order, (i) a start codon (a translation initiation sequence), (ii) an ORF (open reading frame) encoding an expression sequences (a coding sequence, e.g., GFP), (iii) a UTR, and (iv) a poly-A sequence that is greater than 30 nucleotides (i.e., at least 30 consecutive adenosine nucleotides) Claims 1, 18, 23; paragraphs [0010-0013, 0033-0034, 0079, 0081, 0199-0205]; Figs. 2 and 4).
In regards to claims 2-3, Stewart discloses that the poly-A can be at least 60 nucleotides which overlaps with both at least 60 (claim 2) and about 40 to about 150 (claim 3).
In regards to claim 4, in regards to “at least two, three, or more poly(A) sequences”, the specification does not define what multiple poly-A sequences are, and as a result, this has been broadly interpreted as any number of adenosine nucleotides (greater than at least 30 as specified in claim 1). To this end, Stewart discloses that the poly-A sequence can be at least 3000 nucleotides (paragraph [0207]).
In regards to claim 7, Stewart discloses that the circular RNA can have a total size of 200 nucleotides (paragraph [0142]) and therefore, the UTR would have a length of less than about 200 nucleotides.
In regards to claim 15, it is noted that the claims do not require a specific coding sequence, but only generically states that the G/C content is at least about 55%, 60%, or 65%. Turning to the art, Stewart discloses that in embodiments the expression sequence can be GFP which has the sequences of SEQ ID NO: 2 (paragraph [0363]). As evidenced by Vector Builder, SEQ ID NO: 2 has a G/C content of 61.79% which overlaps with the claimed range.
In regards to 16, Stewart discloses that the coding sequence may code a therapeutic protein (paragraphs [0151-0152]) and is therefore, suitable for use in the treatment or prevention of disease.
In regards to claim 17, Stewart discloses that the peptide can at least be an antibody (paragraphs [0151-0152]).
In regards to claim 18, Stewart discloses that the circular RNA is cap-independent (paragraph [0220]).
In regards to claim 19, Stewart discloses that the circular RNA can comprise an IRES (paragraph [0167]).
In regards to claims 33-35, Stewart discloses that the circular RNA may comprise modified nucleotides (e.g., pseudo-uridine, N(6)methyladenosine (m6A))(paragraphs [0005-0006). As these are a further embodiment, and synthetic nucleotides, a person of ordinary skill in the art would have recognized that the circular RNA as disclosed by Stewart could comprise only natural and therefore, unmodified RNA.
In regards to claim 52, Stewart discloses that the circular RNA is derived from a linear RNA (paragraphs [0015, 0272]). As above, Stewart discloses that the RNA comprising, in order, (i) a start codon (a translation initiation sequence), (ii) an ORF (open reading frame) encoding an expression sequences (a coding sequence, e.g., GFP), (iii) a UTR, and (iv) a poly-A sequence that is greater than 30 nucleotides (i.e., at least 30 consecutive adenosine nucleotides) Claims 1, 18, 23; paragraphs [0010-0013, 0033-0034, 0079, 0081, 0199-0205]; Figs. 2 and 4). Stewart discloses that the circular RNA is formed by self0ligation with 3’ and 5’ self-splicing permuted intron-exon sequences (paragraph [0277]).
In regards to claim 65, Stewart discloses a pharmaceutical composition comprising the circular RNA (claim 18).
In regards to claim 97, since as above, circular RNAs are made from linear RNAs (paragraphs [0015, 0272, 0357-0361]), which results in combinations of circular and linear DNA during the circularization process.
In regards to claim 109, Stewart discloses that the composition can be administered to a subject (paragraph [0353]; claim 22) for treating disease (paragraph [0055]).
In regards to claim 132, Stewart discloses that the circular RNA is prepared (thus, obtained) by providing and circularizing a linear RNA (paragraph [0015, 0263-0265]). In an embodiment, Stewart discloses that the RNA was circularized by using SplintR ligase, which as evidenced by NEB requires a buffer (first page).
Therefore, Stewart anticipates the invention as claimed.
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.
Claim 106 is rejected under 35 U.S.C. 103 as being unpatentable over Stewart et al. (US20200306286A1) in view of Armstrong et al. (US20180148717A1) and Turner et al. (US20080161195A1).
Stewart anticipates claim 1 as discussed above.
In regards to claim 106, Stewart does not explicitly teach a kit comprising the circular RNA.
However, a person of ordinary skill in the art would have been motivated to incorporate the circular RNA in a kit for transportation for clinical or research application, as taught by Armstrong (paragraph [0094]). A person of ordinary skill in the art would have been motivated to include a liquid vehicle for solubilization in order to maintain a stable environment circular RNA while in a kit. Furthermore, because Armstrong teaches that circular RNAs can be incorporated into a kit (claim 43), and because Turner teaches that kits can contain liquid buffers for maintaining reagents (e.g., circular RNA) in a kit (paragraph [0092]), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Stewart, Armstrong and Turner render the invention unpatentable as claimed.
Claim 113 is rejected under 35 U.S.C. 103 as being unpatentable over Stewart et al. (US20200306286A1) in view of Ulshöfer et al. (Methods, available online April 22, 2021)
Stewart anticipates claim 1 as discussed above.
In regards to claim 113, Stewart uses size-based purification of circular DNA (paragraph [0462]), not affinity-based purification.
However, a person of ordinary skill in the art would have been motivated to utilize affinity purification because Ulshöfer teaches affinity purification is advantageous because it can be combined with other purification techniques, allows estimation of circular RNA size, is suitable for studying circular RNA translation, and has single-molecular resolution (Table 1, p40). Furthermore, because Ulshöfer teaches that circular RNA can be readily filtered by affinity purification (Fig. 2, p38-39), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Stewart and Ulshöfer render the invention unpatentable as claimed.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Courel et al. (eLife, 2019).
No claims are allowed.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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