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 .
Application Status
Applicant’s remarks filed May 15, 2026 are acknowledged. Claims 1-20 are pending.
Restriction/Election
Applicant’s election without traverse of Invention I (claims 1-16) in the reply filed on May 15, 2026 is acknowledged. Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Claims 1-16 are under consideration hereinafter.
Priority
The certified copy of CN202310032709.9 has been received. The effective filing date of claims 1-16 under examination is January 10, 2023.
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 - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is defective. USPTO records indicate that the size of the sequence listing received September 27, 2023 is “65,016 bytes.”
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 incorporation by reference paragraph, 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.
Specification
The specification is objected to because of the following informalities:
The specification recites “SQE ID NO.” and “SQE ID NOs.” in several locations throughout the specification. Each instance should be amended to recite “SEQSEQ
Appropriate correction is required.
Claim Objections
Claims 1-2, and 7 are objected to because of the following informalities:
Claim 1 recites “a same gene.” It is reasonably clear that the claim intends for the full-length intron, the downstream exon, and the upstream exon to be from the same gene. The claim should be amended to recite “the[[a]] same gene,” accordingly.
Claim 2 recites “SQE ID NOs. 1 and 3-8,” which should be amended to recite “SEQ
Claim 2 also recites “an amino acid sequence of the urate oxidase coding fragment.” It is clear based on the content of the claims, that the recombinant nucleic acid molecule is composed of DNA nucleotides. As such, the phrase should be amended to recite “an amino acid sequence encoded by[[of]] the urate oxidase coding fragment.”
Claim 7 recites “at least 97% similarity with SRL.” It would be preferable to recite “at least 97% similarity with the amino acid sequence SRL.”
Appropriate correction is required.
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 1-16 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 “the circular RNA being capable of expressing a urate oxidase in cells.” It is not clear what structure(s) the recombinant nucleic acid molecule must have, in order to encode such a circular RNA. For example, it is not clear whether the recombinant nucleic acid molecule must merely comprise a ribosome binding site (e.g., an IRES fragment) and a coding sequence for urate oxidase, or whether the recombinant nucleic acid molecule must comprise additional unrecited structures/elements which facilitate circularization, linearization, expression in cells, etc., e.g., specific signal peptides, regulatory sequences, and the like. Because it is not clear what structure(s) the recombinant nucleic acid molecule must have in order to encode a circular RNA capable of expressing a urate oxidase in cells, the claim is indefinite.
Claims 2-16 are rejected for depending from claim 1 and failing to remedy the indefiniteness. In the interest of compact prosecution, and for the purposes of prior art, the structures presently recited in claim 1 will be interpreted as encoding a circular RNA capable of expressing a urate oxidase in cells.
Claim 1 recites “an intron fragment which includes a full-length intron.” This phrase is confusing, because it is not clear how an intron “fragment,” i.e., a portion of an intron, could “include a full-length intron.” The structure required of element (a) is not clear, and therefore, the structure required of the recombinant nucleic acid molecule is unclear.
Claims 2-16 are rejected for depending from claim 1 and failing to remedy the indefiniteness. In the interest of compact prosecution, and for the purposes of prior art, claim 1 will be interpreted as encompassing any intron or fragment thereof.
Claims 2, 5, 7, 9-10, and 12 recite various percent “similarity,” e.g., “95% similarity with any one of S[E]Q ID NOs. 1 and 3-8” in claim 2. The specification does not provide a definition for sequence “similarity,” or provide a metric which would allow the skilled artisan to determine the degree of similarity required to the recited sequences to be considered 95%, 99%, or 100% “similar.” There are several known programs for similarity searching as it would be understood by the skilled artisan; however, it is not clear that the skilled artisan would achieve the same level of “similarity” when comparing sequences in one program and another. Furthermore, sequence “similarity” is not equivalent to sequence “identity” to the skilled artisan. It is not clear whether a sequence which is 100% identical to a recited sequence would be excluded from the claims, because an identical sequence would not “similar.” Because there is no clear definition or metric for “similarity” based on the speciifcation or prior art, and because this term is not equivalent to “identity,” and therefore, may exclude certain sequences with certain levels of identity, the skilled artisan would not known which sequences meet the scope of the claims.
In the interest of compact prosecution, and for the purposes of prior art, claims 2, 5, 7, 9-10, and 12 will be interpreted as referring to percent “identity” to a recited sequence. It is noted that this term is not used in the specification; however, it is the only practicable way to interpret the present scope of the claims for prior art analysis given the indefiniteness described above.
Claim 3 recites “a signal peptide that is configured to facilitate secreting the urate oxidase outside of the cells.” It is not clear whether any signal peptide which facilitates protein secretion outside of cells is encompassed by the claim, or whether the signal peptide must be “configured” in some way which is particular for the recited urate oxidase. Because the structure(s) the signal peptide must have to facilitate secretion of the urate oxidase are unclear, the claim is indefinite.
Claim 4 is rejected for depending from claim 3 and failing to remedy the indefiniteness. In the interest of compact prosecution, and for the purposes of prior art, claim 3 will be interpreted as encompassing any signal peptide which facilitates protein secretion outside of cells.
Claim 5 recites “The recombinant nucleic acid according to claim 6, wherein… the signal peptide has at least 95% similarity with any one of SEQ ID NOs. 11-29.” Claim 6 recites a “signal positioning peptide,” but does not recite a “signal peptide.” It is not clear whether “signal peptide” in claim 5 intends to refer to the “signal positioning peptide,” or whether claim 5 is referring to some unrecited element.
In the interest of compact prosecution, and for the purposes of prior art, claim 5 will be interpreted as depending from claim 3, which refers to a “signal peptide.”
Claim 6 recites “a signal positioning peptide that is configured for positioning the urate oxidase to a peroxisome.” It is not clear whether any signal positioning peptide which facilitates protein positioning to a peroxisome is encompassed by the claim, or whether the signal positioning peptide must be “configured” in some way which is particular for the recited urate oxidase. Because the structure(s) the signal positioning peptide must have to position the urate oxidase to a peroxisome are unclear, the claim is indefinite.
Claims 5 and 7 are rejected for depending from claim 6 and failing to remedy the indefiniteness. In the interest of compact prosecution, and for the purposes of prior art, claim 6 will be interpreted as encompassing any signal positioning peptide which facilitates protein positioning to a peroxisome.
Claim 12 recites three “wherein” clauses, which are not separated by a conjunction (“and,” “or,” or “and/or,” for example). It is not clear whether only one of the “wherein” clauses is required, or whether all of the wherein clauses are required.
For the purposes of prior art, claim 12 will be interpreted hereinafter as requiring at least one of the “wherein” clauses.
Claim 13 recites “a 5’ homology arm sequence and a 3’ homology arm sequence positioned between the E2 fragment and the E1 fragment.” Based on claim 1, it does not appear that the E2 fragment and the E1 fragment are positioned next to one another, such that one could position a 5’ homology arm sequence and a 3’ homology arm sequence between the fragments. Even in a circular recombinant nucleic acid molecule (e.g., a plasmid or vector), the intron fragment intervenes the E2 fragment and the E1 fragment. The structure required of claim 13 is unclear.
In the interest of compact prosecution, and for the purposes of prior art, claim 13 will be interpreted as requiring a 5’ homology arm sequence and 3’ homology arm sequence, because the spatial relationship is not clear.
Claims 15-16 recite a linear and a circular RNA, respectively, which is “produced based on the recombinant nucleic acid molecule according to claim 1.” It is not clear based on the claims or specification, what structures are conferred to the linear or circular RNA by virtue of their production from the recombinant nucleic acid molecule. The prior art teaches that different RNA species are produced from such a production process, and these species do not necessarily comprise each of the elements of the recombinant nucleic acid molecule from which the RNA is produced. See Wesselhoeft (Wesselhoeft et al., 2018, Nature Communications, (2018)9:2629, pg. 1-10; pg. 2, right col.; Figs. 1-2). The structure(s) required of the linear and circular RNA of claim 15-16 by virtue of their production from the recombinant nucleic acid molecule are unclear.
In the interest of compact prosecution, and for the purposes of prior art, a generic recitation of a linear or circular RNA product produced from a circular RNA with the elements of claim 1 will be interpreted as meeting the scope of claims 15-16.
Improper Markush Grouping
Claim 8 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claim 8 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use. The grouping recites various genes encoding proteins, and also recites “an aptamer for eIF4G.” An aptamer is not a gene encoding a protein, and I) would not be recognized as in the same art-recognized class as genes encoding a protein, or as functionally equivalent and having a common use based on the specification or art, and II) would not be understood to share a substantial structural feature with genes encoding a protein and a common use that flows therefrom.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 15-16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 15-16 recite “RNA which is produced based on the recombinant nucleic acid molecule according to claim 1.” The recombinant nucleic acid molecule according to claim 1 is composed of DNA nucleotides. Therefore, claims 15-16 each substitute a recombinant nucleic acid molecule composed of DNA nucleotides, for an RNA molecule. The claims fail to include all the limitations (i.e., the DNA form) of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Notice to Joint Inventors
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 Rejections - 35 USC § 103 – Sun in view of Hartman
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.
Claims 1-2, and 6-16 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (Sun et al., US 2022/0177910 A1, published 9 June 2022) in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013).
Regarding claims 1-2, Sun teaches a recombinant nucleic acid molecule for making a circular RNA which expresses a coding sequence in cells ([0025]). Sun teaches the recombinant nucleic acid molecule comprises the following elements operably linked to each other and arranged, in a 5' to 3' direction, in the following order (a) an intron; (b) an E2 fragment which includes a downstream exon of the full-length intron; (c) an internal ribosome entry site (IRES) fragment; (d) a coding fragment; and (e) an E1 fragment which includes an upstream exon of the full-length intron; wherein the full-length intron, the downstream exon, and the upstream exon are from the same gene (“modified ribozyme-catalyzed method from Anabaena tRNA introns… E1 and E2 of the PIE system of Anabaena tRNA,” [0006]-[0007]; Fig. 1).
Sun teaches that the recombinant nucleic acid molecule “has important application value in many fields like… mRNA-based gene therapy” (Abstract). Sun teaches multiple examples of encoding various proteins in such recombinant nucleic acid molecules, and expressing the proteins in eukaryotic cells (see Examples). Sun teaches that the use of the recombinant nucleic acid molecule has advantages over using linear RNA, for example, increased expression of the target protein in eukaryotic cells, higher stability and expression durability ([0007]-[0008]; [0025]; [0125]).
Sun does not teach that the recombinant nucleic acid molecule comprises a urate oxidase coding fragment.
However, Hartman teaches a recombinant nucleic acid molecule comprising a urate oxidase coding fragment (cols. 2, 7-8; Fig. 2), wherein the fragment encodes an amino acid sequence at least 95% identical to instant SEQ ID NO: 7. See attached alignment between instant SEQ ID NO: 7 and Hartman SEQ ID NO: 7 in Appendix I. Hartman teaches that humans do not produce enzymatically active urate oxidase (“uricase”), and as a consequence, excessive concentrations of uric acid in the blood can lead to painful arthritis (gout), tophi, and renal failure (col. 1). Hartman teaches that uricase administration can alleviate hyperuricemia, but is associated with adverse immunologic response (col. 1). Hartman’s uricase, in contrast, is tolerated in human subjects, and effectively lowers uric acid levels (cols. 20-22).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the coding fragment in the recombinant nucleic acid molecule of Sun, for a urate oxidase coding fragment taught by Hartman. It would have amounted to substituting two known coding fragments suitable for expression in cells, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in substituting the coding fragments because Sun demonstrates that the recombinant nucleic acid molecule can be used to express proteins in eukaryotic cells, and because Hartman, likewise, teaches vectors encoding the urate oxidase which are used for expression in cells. Thus, the skilled artisan would have had a reasonable expectation that Sun’s recombinant nucleic acid molecule could be used to express the urate oxidase coding fragment of Hartman. The skilled artisan would have had substantial motivation to substitute the coding fragments given the advantages of using circular RNAs to expressing coding fragments taught by Sun ([0007]-[0008]; [0025]; [0125]), and the therapeutic relevance of the urate oxidase coding fragment taught by Hartman.
Regarding claims 6-7, Hartman’s urate oxidase coding fragment set forth in SEQ ID NO: 7 encodes a signal positioning peptide element which is C-terminal to the urate oxidase coding fragment, wherein the amino acid sequence of the signal positioning peptide element is “SRL” (col.s 23-25), and which, under the obviousness grounds above, would be positioned between the IRES fragment and the urate oxidase coding fragment in a circular recombinant nucleic acid molecule encompassed by the claims.
Regarding claims 8-10, Sun teaches an IRES element derived from CVB3 ([0144]; SEQ ID NO: 8, “CVB3,” [0175]). As shown in the attached alignment in Appendix I, the DNA sequence of Sun’s CVB3 IRES element is at least 95% identical to instant SEQ ID NO: 40.
Regarding claims 11-12, Sun teaches a recombinant nucleic acid molecule which comprises an intron of the pre-tRNALeu gene of genus Anabaena wherein the nucleotide sequence of the intron is at least 95% identical to instant SEQ ID NO: 41 ([0175]). Specifically, the “3’ intron” corresponding to SEQ ID NO: 4 is identical to nts 119-249 of instant SEQ ID NO: 41, and the “5’ intron” corresponding to SEQ ID NO: 16 is identical to nts 2-115 of instant SEQ ID NO: 41, such that Sun’s intron has identity to 245/249 nts, or 98% identity, to SEQ ID NO: 41 ([0175]). Sun’s recombinant nucleic acid molecule also comprises an E2 fragment which includes a downstream exon of the aforementioned intron which is 100% identical to instant SEQ ID NO: 42 (“second exon (E2)” corresponding to SEQ ID NO: 5, [0175]), and an E1 fragment which includes a upstream exon of the aforementioned intron which is 100% identical to instant SEQ ID NO: 46 (“first exon (E1)” corresponding to SEQ ID NO: 15, [0175]). See attached alignments in Appendix I.
Regarding claim 13, Sun teaches the nucleic acid molecule comprises a 5’ homology arm sequence and 3’ homology arm sequence (“5’ Homology arm,” “3’ Homology arm,” Fig. 1).
Regarding claim 14, Sun teaches a promoter which is capable of initiating in vitro transcription of the recombinant nucleic acid molecule, and which is positioned upstream of the intron fragment (“T7,” Fig. 1).
Regarding claims 15-16, Sun teaches linear and circular RNA produced based on the recombinant nucleic acid molecule (Fig. 1).
Claim Rejections - 35 USC § 103 – Sun and Hartman in view of Hamilton
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (Sun et al., US 2022/0177910 A1, published 9 June 2022) and Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013) as applied to claims 1-2, and 6-16, in further view of Hamilton (Hamilton et al., 2018, Cell Reports, 22, 1-7, and Supplemental Experimental Procedures).
The teachings of Sun and Hartman are described above and applied hereinafter as to claims 1-2, and 6-16.
Neither Sun nor Hartman teach a signal peptide element which meets the limitations of claims 3-5.
However, Hamilton teaches an IL-2 signal peptide element which is positioned upstream of a coding fragment for a therapeutic protein (“Signal peptide sequence,” Fig. 1; Supplemental Experimental Procedures, pg. 1). Hamilton teaches the amino acid sequence of the IL-2 signal peptide element, which has 100% identity to instant SEQ ID NO: 11 (“MYRMQLLSCIALSLALVTNS,” Supplemental Experimental Procedures, pg. 1). Hamilton teaches the IL-2 signal peptide element facilitates secretion of the therapeutic protein (Supplemental Experimental Procedures, pg. 1; Fig. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the recombinant nucleic acid molecule rendered obvious above with the IL-2 signal peptide element of Hamilton, such that it would be positioned between the IRES fragment and the urate oxidase coding fragment. It would have amounted to including a known element suitable for facilitating secretion of a therapeutic protein, in an obvious vector, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success, and would have been motivated to modify the recombinant nucleic acid molecule, because means to include the IL-2 signal peptide element were known, and because based on Hamilton, such a modification would be reasonably expected to facilitate secretion of the urate oxidase protein produced from the recombinant nucleic acid molecule.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
U.S. Patent No. 12,247,202
Claims 1-2, 6-8, 11-12, and 14-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,247,202 in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow.
Patented claim 1 recites a recombinant nucleic acid molecule for making a circular RNA, which, with the exception of the urate oxidase coding fragment and signal positioning peptide of the instant claims, is a species of the recombinant nucleic acid molecule of instant claims 1-2, 6-8, and 11-12.
Regarding the urate oxidase coding fragment and signal positioning peptide of claims 1-2, 6-8, and 11-12, the teachings of Hartman are described above and applied hereinafter. The obviousness of modifying the patented recombinant nucleic acid molecule so as to include an urate oxidase coding fragment and signal positioning peptide which meets the limitations of instant claims 1-2, 6-8, and 11-12 is described above and applied hereinafter.
Regarding claims 14-16, patented claim 1 recites “in vitro transcription template [which] includes the full-length intron” of the DNA molecule, which inherently requires a promoter (i.e., a sequence which facilitates transcription machinery) preceding the intron. Patented claim 1 also recites a “linear RNA” and a “circular RNA,” which meets the limitations of claims 15-16.
Claims 3-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,247,202 in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013) and Hamilton (Hamilton et al., 2018, Cell Reports, 22, 1-7, and Supplemental Experimental Procedures). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow.
Regarding claims 3-5, the teachings of Hamilton are described above and applied hereinafter. The obviousness of modifying the patented recombinant nucleic acid molecule so as to include an IL-2 signal peptide taught by Hamilton is described above and applied hereinafter.
Claims 9-10, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,247,202 in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013) and Sun (Sun et al., US 2022/0177910 A1, published 9 June 2022). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow.
Regarding the IRES sequence recited in claims 9-10, and the 3’ and 5’ homology arms recited in claim 13, the teachings of Sun are described above and applied hereinafter.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the patented recombinant nucleic acid molecule to comprise the CVB3 IRES sequence and 3’ and 5’ homology arm sequences taught by Sun. It would have amounted to modifying a known recombinant nucleic acid molecule using elements of a substantially identical recombinant nucleic acid molecule for the same purpose, by known means to yield predictable results. The skilled artisan would have been motivated to modify the recombinant nucleic acid molecule because Sun and the patented claims are directed to substantially identical molecules, and Sun teaches specific sequences of elements of the patented molecule (i.e., a CVB3 IRES sequence), and elements compatible with the patented molecule (i.e., 3’ and 5’ homology arms).
Application No. 18/983,447
Claims 1-2, 6-8, 11-12, and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/983,447 in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending claim 1 recites a recombinant nucleic acid molecule for making a circular RNA, which, with the exception of the urate oxidase coding fragment and signal positioning peptide of the instant claims, is a species of the recombinant nucleic acid molecule of instant claims 1-2, and 6-7.
Regarding the urate oxidase coding fragment and signal positioning peptide of claims 1-2, and 6-7, the teachings of Hartman are described above and applied hereinafter. The obviousness of modifying the co-pending recombinant nucleic acid molecule so as to include an urate oxidase coding fragment and signal positioning peptide which meets the limitations of instant claims 1-2, and 6-7 is described above and applied hereinafter.
Co-pending claim 5 meets the limitations of instant claim 8. Co-pending claims 7, and 9-10 meet the limitations of instant claims 11-12. Co-pending claims 2-3 meet the limitations of instant claims 14-16.
Claims 3-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/983,447 in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013) and Hamilton (Hamilton et al., 2018, Cell Reports, 22, 1-7, and Supplemental Experimental Procedures). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow.
Regarding claims 3-5, the teachings of Hamilton are described above and applied hereinafter. The obviousness of modifying the co-pending recombinant nucleic acid molecule so as to include an IL-2 signal peptide taught by Hamilton is described above and applied hereinafter.
Claims 9-10, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/983,447 in view of Hartman (Hartman et al., US 8,465,735 B2, published 18 June 2013) and Sun (Sun et al., US 2022/0177910 A1, published 9 June 2022). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow.
Regarding the IRES sequence recited in claims 9-10, and the 3’ and 5’ homology arms recited in claim 13, the teachings of Sun are described above and applied hereinafter.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the co-pending recombinant nucleic acid molecule to comprise the CVB3 IRES sequence and 3’ and 5’ homology arm sequences taught by Sun. It would have amounted to modifying a known recombinant nucleic acid molecule using elements of a substantially identical recombinant nucleic acid molecule for the same purpose, by known means to yield predictable results. The skilled artisan would have been motivated to modify the recombinant nucleic acid molecule because Sun and the co-pending claims are directed to substantially identical molecules, and Sun teaches specific sequences of elements of the co-pending molecule (i.e., a CVB3 IRES sequence), and elements compatible with the co-pending molecule (i.e., 3’ and 5’ homology arms).
Conclusion
No claims are allowed.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
