DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 8-20-26.
Claims 1-4, 6, 8-10, 13-15, 17-19, 21, 23, 24, 27, 28, 30, 32-35 are pending in the instant application.
Election/Restrictions
Claims 1-4, 6, 8-10, 13-15, 17, 30, 32-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8-20-26.
Applicant’s election without traverse of Group III, claims 18-19, 21, 23-24, and 27-28, drawn to linear polyribonucleotide compositions, in the reply filed on 8-20-26 is acknowledged.
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 21 and 23 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.
It is unclear how the claimed linear polyribonucleotide can comprise both complementary and non-complementary sequences have between 5 and 50 ribonucleotides and have between 50% and 100% sequence complementarity.
Appropriate clarification is required.
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 8-12, 17, 21-23, 25-30 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.
The breadth of the claims:
The claims are drawn to a linear polyribonucleotide, or a DNA encoding the linear polyribonucleotide, comprising a 5' self-cleaving ribozyme, a 5' annealing region comprising a 5' complementary region, a polyribonucleotide cargo, a 3' annealing region comprising a 3' complementary region; and a 3' self-cleaving ribozyme, which 5' complementary region and 3' complementary region have a free energy of binding of less than -5 kcal/mol, and/or a Tm of binding of at least 10°C and have between 5 and 50 ribonucleotides and have between 50% and 100% sequence complementarity or optionally include no more than 10 mismatches between them, and which 5' and/or 3' self-cleaving ribozyme optionally comprise a Hammerhead, Hairpin, Hepatitis Delta Virus ribozyme (HDV), Varkud Satellite (VS), glmS ribozyme, Twister, Twister sister, Hatchet, or Pistol, and which 5' annealing region optionally further comprises a 5' non-complementary region that has between 5 and 50 ribonucleotides and is located 5' to the 5' complementary region, and which 3' annealing region optionally further comprises a 3' non-complementary region that has between 5 and 50 ribonucleotides and is located 3' to the 3' complementary region, which non-complementary regions have between 0% and 50% sequence complementarity and/or a free energy of binding of greater than -5 kcal/mol; and/or a Tm of binding of less than 10°C, which linear polyribonucleotide further comprises at least one coding sequence encoding a polypeptide, optionally wherein the polypeptide encoded in the genome of a vertebrate, invertebrate, plant, or microbe, and/or a therapeutic polypeptide, a plant-modifying polypeptide, or an agricultural polypeptide, and optionally further comprises an additional element selected from an internal ribosome entry site (IRES) or a 5' UTR sequence located 5' to and operably linked to the coding sequence, optionally with intervening ribonucleotides between the IRES or 5' UTR sequence and the coding sequence, and further comprises a 3' UTR sequence, located 3' to and operably linked to the coding sequence, optionally with intervening ribonucleotides between the 3' UTR and the coding sequence, and at least one non-coding sequence; or a combination of at least one coding sequence encoding a polypeptide and at least one non-coding sequence, which linear polyribonucleotide optionally further comprises a spacer region of at least 5 polyribonucleotides in length between the 5' annealing region and the polyribonucleotide cargo, optionally wherein the spacer region comprises a polyA sequence or a polyA-C sequence, which DNA sequence encoding the linear polyribonucleotide optionally further comprises a heterologous promoter operably linked to the DNA sequence encoding the linear polyribonucleotide, optionally comprising a heterologous promoter optionally comprising a T7, T6, T4, T3, SP3 or SP6 promoter.
The Teachings in the specification:
Example 1: Construct design
[0370] This example describes the design of the DNA construct (SEQ ID NO: 8). A schematic depicting the design of the DNA construct is provided in FIG. 1. The construct encodes, from 5'-to-3': a promotor capable of recruiting an RNA polymerase for RNA synthesis (SEQ ID NO: 1); a 5' self- cleaving ribozyme that cleaves at its 3' end (SEQ ID NO: 17); a 5' annealing region (SEQ ID NO: 18); an internal ribosome entry site (IRES) (SEQ ID NO: 20); a coding region encoding a polypeptide (SEQ ID NO: 21); a 3' annealing region (SEQ ID NO: 19); and a 3' self-cleaving ribozyme that cleaves at its 5' end (SEQ ID NO: 22).
[0371] The DNA construct was transcribed to produce a linear RNA (SEQ ID NO: 9) including, from 5'-to-3': a 5' self-cleaving ribozyme that cleaves at its 3' end (SEQ ID NO: 2); a 5' annealing region (SEQ ID NO: 3); an internal ribosome entry site (IRES) (SEQ ID NO: 5); a coding region encoding a polypeptide (SEQ ID NO: 6); a 3' annealing region (SEQ ID NO: 4); and a 3' self-cleaving ribozyme that cleaves at its 5' end (SEQ ID NO: 7). Upon expression, the linear RNA self-cleaved to produce a ligase-compatible linear RNA having a free 5' hydroxyl and a free 3' monophosphate (SEQ ID NO: 10). The ligase-compatible linear RNA was circularized by addition of an RNA ligase. A schematic depicting the process of circularization is provided in FIG. 2.
Example 5: RNAs are functional
[0379] This example describes functional protein expression from circular RNA generated by the methods described herein. To confirm that the circular RNA generated by the methods described herein remains functional, the expression of luciferase was quantified. Wheat germ extract… TNT T7 Insect Cell Extract Protein Expression System.. and Nuclease Treated Rabbit Reticulocyte Lysate …were incubated for 1 hour with IRES-luciferase circular RNAs (SEQ ID NOs:10, 15, 16, 23) according to the manufacturer's instructions. Each construct includes an IRES selected from CrTMV (SEQ ID NO:11), HCRSV (SEQ ID NO:12), or ZmHSP (SEQ ID NO:13). Luciferase expression was then measured … Circular RNAs generated using the methods described herein were able to drive protein expression…
Example 6: Methods for generating circular RNA with larger cargo in a cell-free system
[0380] This example describes a method for generating RNA constructs for circularization incorporating a larger cargo in a cell-free system.
(FIG. 6). The final RNA sequence contains an IRES element (ZmHSP, SEQ ID NO: 13) and firefly luciferase (SEQ ID NO: 14), producing a final circular RNA 1850 nucleotides in length (SEQ ID NO: 16).
Example 7: Generating circular RNA in a cell-free system
[0383] This example describes a method of producing a circular polyribonucleotide in a cell-free system from a linear polyribonucleotide precursor. In this example, the linear polynucleotide includes a 5' annealing region including a 5' complementary region, and a 3' annealing region including a 3' complementary region, wherein fewer than 10 mismatches occur between the 5' complementary region and the 3' complementary region, and wherein the 5' complementary region and the 3' complementary region have a free energy of binding of less than -5 kcal/mol, and/or wherein the 5' complementary region and the 3' complementary region have a Tm of binding of at least 10°C.
[0384] More specifically, the linear precursor included, operably linked in 5' to 3' direction: (a) a heterologous promoter capable of recruiting an RNA polymerase for RNA synthesis (T7 promoter, SEQ ID: 572); (b) a 5' self-cleaving ribozyme that cleaves at its 3' end (a modified P3 Twister U2A ribozyme, SEQ ID: 595); (c) 5' anncaling region (including a nucleotide sequence from the 5' half of a loop of Eggplant Latent Viroid (ELVd), SEQ ID: 597); (d) a polyribonucleotide cargo comprising a Pepper aptamer sequence (SEQ ID: 599), a ZmHSP101 IRES sequence (SEQ ID: 584), and a Nanoluc open reading frame (SEQ ID: 592); (e) a 3' annealing region (including a nucleotide sequence from the 3' half of a loop of Eggplant Latent Viroid (ELVd), SEQ ID: 598); and (f) a 3' self-cleaving ribozyme that cleaves at its 5' end (a modified P1 Twister Ribozyme, SEQ ID: 596).
[0390] This example describes embodiments of a circular RNA that includes a polynucleotide cargo including one or more coding or expression sequences.
[0392] Examples of these modifications included: (a) replacement of the internal ribosome entry site (IRES) with a 5'UTR sequence (e.g., any one of SEQ ID NOs:600, 601, 602, 603, 604, or 612) 5' and operably linked to the coding sequence, either directly or with intervening sequence; (b) including a 3' UTR sequence (e.g., any one of SEQ ID NOs: 605, 606, 607, 608, 609, 610, 611, or 613) 3' and operably linked to the coding sequence, either directly or with intervening sequence, e.g., including a 3' UTR 3' to and operably linked to the Nanoluc open reading frame in a construct based on that described in Example 1; (c) including in the DNA construct DNA sequence encoding an IRES or a 5' UTR (e.g., any one of SEQ ID NOs: 582, 583, 584, 591, 601, 602, 603, 604., or 612) 5' and operably linked to the coding sequence, as well as a DNA sequence encoding a 3'UTR selected from SEQ ID NOs:605, 606, 607, 608, 609, 610, 611, or 613 3' and operably linked to the polynucleotide cargo.
[0394] The results of the experiment showed that a circular RNA that included modifications flanking the cargo sequence provided increased translation efficiency of a polypeptide-coding cargo sequence. For example, a circular RNA that included both (a) the sTNV 5'UTR (SEQ ID NO: 600) 5' and operably linked to the cargo sequence, and (b) the sTNV 3'UTR (SEQ ID NO: 605) 3' and operably linked to the cargo sequence, had increased translation efficiency compared to the control RNA construct, i.e., ~5-fold higher translation efficiency than control in wheat germ extract, and ~1.2-fold higher translation efficiency than the control construct in insect cell extract. In another example, a circular RNA that included both (a) the TCV 5'UTR (SEQ ID NO: 612) 5' and operably linked to the cargo sequence, and (b) the TCV 3'UTR (SEQ ID NO: 613) 3' and operably linked to the cargo sequence, had increased translation efficiency compared to the control RNA construct, i.e., ~1.5-fold higher translation efficiency than control in insect cell extract, and ~0.9-fold higher translation efficiency than the control construct in wheat germ extract.
Table 12 provides a Summary of Sequences used in Examples 7, 8, and 9 of the specification.
[Emphases added] [Citations omitted].
The specification fails to provide the requisite guidance for making and using
the broad genus of linear polyribonucleotides or circular RNA instantly claimed. As listed above, the specification describes a number of constructs with particular sequences of the linear polyribonucleotide subcomponents arranged in a precise order.
These examples fail to provide a representative number of species adequately describing the broad genus of nucleic acid constructs claimed. Since the disclosure fails to describe the common attributes and characteristics concisely identifying members of the proposed genus of linear polyribonucleotides, and because the claimed genus is highly variant, the description provided is insufficient. One of skill in the art would reasonably conclude that the disclosure fails to provide a concise description of the broad genus of nucleic acid constructs instantly claimed.
Thus, Applicant was not in possession of the broadly claimed genus.
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.
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(s) 18-19, 21, 23-24, and 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jaffrey et al (WO 2018/237372) and Carmona, E. M. (Circular RNA: Design Criteria for Optimal Therapeutical Utility, Doctoral Dissertation, Harvard Library, 100 pages (2019)), the combination in view of Busa et al (Methods, Vol. 196, pages 56-67 (Available online March 2, 2021)).
The claims are drawn to a linear polyribonucleotide, or a DNA encoding the linear polyribonucleotide, comprising a 5' self-cleaving ribozyme, a 5' annealing region comprising a 5' complementary region, a polyribonucleotide cargo, a 3' annealing region comprising a 3' complementary region; and a 3' self-cleaving ribozyme, which 5' complementary region and 3' complementary region have between 5 and 50 ribonucleotides and have between 50% and 100% sequence complementarity or optionally include no more than 10 mismatches between them, and which 5' and/or 3' self-cleaving ribozyme optionally comprise a Hammerhead, Hairpin, Hepatitis Delta Virus ribozyme (HDV), Varkud Satellite (VS), glmS ribozyme, Twister, Twister sister, Hatchet, or Pistol, and which 5' annealing region optionally further comprises a 5' non-complementary region that has between 5 and 50 ribonucleotides and is located 5' to the 5' complementary region, and which 3' annealing region optionally further comprises a 3' non-complementary region that has between 5 and 50 ribonucleotides and is located 3' to the 3' complementary region, which non-complementary regions have between 0% and 50% sequence complementarity, which linear polyribonucleotide further comprises at least one coding sequence encoding a polypeptide, and which linear polyribonucleotide optionally further comprises an additional element selected from an internal ribosome entry site (IRES) or a 5' UTR sequence located 5' to and operably linked to the coding sequence, optionally with intervening ribonucleotides between the IRES or 5' UTR sequence and the coding sequence, and further comprises a 3' UTR sequence, located 3' to and operably linked to the coding sequence, optionally with intervening ribonucleotides between the 3' UTR and the coding sequence, and at least one non-coding sequence; or a combination of at least one coding sequence encoding a polypeptide and at least one non-coding sequence, which linear polyribonucleotide optionally further comprises a spacer region of at least 5 polyribonucleotides in length between the 5' annealing region and the polyribonucleotide cargo, optionally wherein the spacer region comprises a polyA sequence or a polyA-C sequence, which DNA sequence encoding the linear polyribonucleotide optionally further comprises a heterologous promoter operably linked to the DNA sequence encoding the linear polyribonucleotide, optionally comprising a heterologous promoter optionally comprising a T7, T6, T4, T3, SP3, or SP6 promoter.
Jaffrey et al (WO 2018/237372) teach circular RNA molecules generated from linear RNA molecules comprising a nucleic acid sequence encoding a 5’ polymerase promoter, a first self-cleaving ribozyme, a first ligation sequence, an effector molecule, a second ligation sequence, a second self-cleaving ribozyme, and a terminator sequence (Summary of the Invention, pages 4-5, claims 1-25). The ligation sequences remain on either side after cleavage, contain a phosphorylation state and RNA termini modification state recognized by endogenous RNA ligases and circularized (para 0020 on page 6) Self-cleaving ribozymes include Hammerhead, Hairpin, HDV, Twister, Twister Sister, Hatchet, and Pistol ribozymes (para 0032-0039 on pages 15-17). Exemplary internal ribosomal entry sites (IRES) are listed in paragraph 0059, pages 20-21). Promoters include T7, T3 and SP6 RNA polymerases (claim 23).
Jaffrey teaches the concept of RNAs that autocatalytically become substrates for RNA ligation for efficient RNA circularization (Example 1, para 0125-0129, pages 36-38, para 0165-0167, pages 50-51). The RNA molecule may further comprise an internal ribosomal entry site (IRES) operatively coupled to the RNA molecule encoding an effector or cargo sequence (para 0050-0051).
Carmona, E. M. (Circular RNA: Design Criteria for Optimal Therapeutical Utility, Doctoral Dissertation, Harvard Library, 100 pages (2019)) (See IDS filed 5-3-24) teaches uniform end positioning of the 5’ and 3’ RNA termini using a CRC motif for enhancing ligation efficiency. For T4 ligase 1 to function efficiently, the 5’ and 3’ termini of the RNA molecule to be circularized must be in close proximity to each other, with a certain level of freedom at the 5’ and 3’ terminal nucleotides (Page 11). Complement-reverse complement (CRC) motif was designed, which contained 20 nucleotide length of complementary nucleotides at the 5’ and 3’ termini, followed by 10 free and random nucleotides at either end of the molecule, called non-complementary regions (text on page 12, Fig. 2 on page 13). The CRC motif provided for efficient ligation (first full paragraph on page 14). Complementary regions were 10, 20 or 30 nucleotides in length and non-complementary regions were 10, 15 or 20 nucleotides in length. The non-complementary regions comprised of either all adenosines or of a random assortment of non-base paired nucleotides (text on page 15; Fig. 3 on page 16).
Carmona teaches the inclusion of IRES sequences in the linear constructs (Fig. 4 on page 18). The optimization of IRES sequences and their placement within the circular RNA was investigated (pages 32-36). The optimization of 5’ UTRs and 3’ UTRs (including PolyA) in circular RNA was also investigated by Carmona (pages 36-37).
The primary references do not teach the addition of additional spacers in the linear polyribonucleotides or circular RNA.
Busa et al (Methods, Vol. 196, pages 56-67 (Available online March 2, 2021) (IDS filed ) teach in vitro generated circular RNAs using T7 expression vectors. Optimized in vitro circularization constructs comprise additional complementary sequences at the termini to promote circularization (Fig. 2 on page 61). Busa teaches the inclusion of permuted intron-exon splicing constructs consisting of fused partial exons that contain the sequence to be circularized flanked by half intron sequences. The addition of homology arms that flank the half-intron sequences and bring the 5’ and 3’ splice sites into proximity increases splicing efficiency. The inclusion of additional spacers improves splicing efficiency even more, according to Busa (Section 6.2 on page 62).
It would have been obvious to design and optimize the instantly claimed linear polyribonucleotide constructs for generating circular RNA because all of the components and the optimization of their placements within the linear polyribonucleotide constructs were well known and routinely used in the prior art, as illustrated in the combined teachings of Jaffrey, Carmona and Busa. One of ordinary skill in the art would have reasonably expected the instantly claimed linear polyribonucleotide to form circular RNA showing increased stability and expression of cargo protein or polypeptides.
For these and the aforementioned reasons, the instant invention would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention.
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.
Claims 18-19, 21, 23-24, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,845,950. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to nucleic acid constructs or vectors for making circular RNA comprising 5’ and 3’ self-cleaving ribozymes, an internal ribosome entry site (IRES), a protein coding region, a promoter, and spacer sequences for increasing splicing efficiency.
Claims 18-19, 21, 23-24, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,981,909. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to nucleic acid constructs or vectors for making circular RNA comprising 5’ and 3’ complementary regions, 5’ and 3’ self-cleaving ribozymes, an internal ribosome entry site (IRES), a protein coding region, a promoter, and spacer sequences for increasing splicing efficiency.
Claims 18-19, 21, 23-24, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-21 of U.S. Patent No. 11,203,767. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compositions comprising nucleic acid constructs or vectors for making circular RNA comprising 5’ and 3’ complementary regions, 5’ and 3’ self-cleaving ribozymes, an internal ribosome entry site (IRES), a protein coding region, a promoter, and spacer sequences for increasing splicing efficiency.
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
10-6-26
/JANE J ZARA/Primary Examiner, Art Unit 1637
