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 .
Applicant’s amendments to the claims filed on September 8, 2025 have been received and entered. Claims 1-61, 63-66, 68, 71-87, 93, 96-119, 123-128 and 131-158 have been canceled, while claims 62, 120-122 have been amended.
Claims 62, 67, 69-70, 88-92, 94-95, 120-122, 129 and 130 are pending in the instant application.
Priority
This application is a continuation of application no 15/560,968 filed on 09/22/2017, which is a 371 of PCT/US2016/024353 filed on 03/25/2016, which claims priority from US provisional applications 62/244,572 filed on 10/21/2015; 62/220,815 filed on 09/18/2015; 62/210,392 filed on 08/26/2015; 62/184,103 filed on 06/24/2015; 62/159,932 filed on 05/11/2015; 62/141,810 filed on 04/01/2015; 62/138,939 filed on 03/26/2015; and 62/138,273 filed on 03/25/2015.
It is noted that the amended claim 62 now recite gRNA molecule comprises a 3' polyA tail consisting of 10 or 20 adenine nucleotides. The disclosure of the prior-filed application, US provisional Application no. 62/220,815; 62/210,392; 62/184,103; 62/159,932; 62/141,810; 62/138,939; and 62/138,273, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for amended claim 1 of this application.
The provisional application no62/220,815; 62/210,392; 62/184,103; 62/159,932; 62/141,810; 62/138,939; and 62/138,273 discloses a similar strategy to add polyA tail to the 3’ end of the gRNA but does not describe using a 3’ polyA tail consisting of 10 or 20 adenine nucleotides. Consequently, there is no written description for this limitation in above mentioned provisional application. In case if applicants have evidence to support otherwise, applicants are invited to indicate page and line number for the written support specifically for using a 3’ polyA tail consisting of 10 or 20 adenine nucleotides as recited in amended claim 62 of the instant application. It is noted that subject matter of claim 62 is explicitly disclosed in US provisional application no 62/244,572, dated 10/21/2015. Therefore, the effective filing date for instant claims 62, 67, 69-70, 88-92, 94-95, 120-122, 129 and 130 is 10/21/2015.
Claims 62, 67, 69-70, 88-92, 94-95, 120-122, 129 and 130 are under consideration.
Maintained & New Claim Rejections - 35 USC § 103- necessitated by amendments
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 62, 69, 129 and 130 are rejected under 35 U.S.C. 103 as being unpatentable over Jinek et al (WO/2013/176772, dated 11/23/2013) as evidenced by Jinek et al (eLife, 2013, e00471, 1-9, IDS) and Janicke et al (RNA, 2012, 18:1289–1295, IDS)/Meissner (US20160348073, EFD 3/27/2015) in view of Epicenter poly(A) polymerase kit, (lit 251, cat.# PAP5104H, 10/2012, 1-5, IDS).
Claims are directed to a composition comprising: a gRNA molecule comprising a targeting domain that is complementary to a target domain from a gene expressed in a eukaryotic cell, wherein the gRNA molecule comprises a 3' polyA tail consisting of 10 or about 20 adenine nucleotides; and is complexed with a Cas9 protein.
With respect to claims 62, 69, Jinek teaches a composition comprising a DNA-targeting RNA polynucleotide (also referred herein as gRNA or, see para. 130) that provides target specificity to the complex by comprising a nucleotide sequence that is complementary to a sequence of a target DNA (see para. 20, 449, 493-494, 517, 533-534, 553, 631 and 567). Jinek further teaches that DNA-targeting RNA (gRNA) may include a 5' cap (e.g., a 7-methylguanylate cap (m7G)) and a 3' polyadenylated tail (i.e., a 3' poly (A) tail) (see para. 133, 134, 386, 387, 426, 444). Jinek teaches a composition comprising DNA-targeting RNA polynucleotide (also referred herein as gRNA or, see para. 130) provides target specificity to the complex by comprising a nucleotide sequence that is complementary to a sequence of a target DNA and a polynucleotide encoding the same site-directed modifying polypeptide, wherein the site-directed modifying polypeptide comprises an amino acid of Cas9 as set forth in figure 3 (see para. 20 and 192). Regarding claims 129-130, Jinek teaches use of the composition for gene editing or to treat a disease (see para. 261).
Jinek et al differ from claimed invention by not adding 3’ end PolyA tail of consist of 10 or 20 adenine nucleotides.
Janicke discloses addition of a poly (A)-tail to the 3’ termini of RNA molecules influence stability, and efficiency of translation. It is further disclosed that changes in the length of the poly (A)-tail have long been recognized as reflective of the switch between translational silence and activation (abstract). Janicke further discloses in vitro transcripts with an estimated average poly(A)-tail length of ~15, ~45, ~65, and ~115 residues (see Supplemental Fig. A) with an estimated poly(A)-tail length of ~20 adenine (see page 1291, col. 1, para. 1). These assertions are further supported by Meissner who teaches that the RNAs may be modified to comprise a 5' cap (para. 303) and a 3' polyA tail (307). Meissner teaches that the polyA tail may be of 10 or 20 adenine nucleotides (see para. 307). Epicenter provided Poly(A) Polymerase Tailing Kit was developed for the rapid and efficient addition of poly(A)-tails to the 3′ end of any RNA. Polyadenylation increases the stability of RNA in eukaryotic cells. The method allows Poly(A) Polymerase that uses ATP as a substrate for template independent addition of adenosine monophosphates to the 3′-hydroxyl termini of RNA molecules. It further discloses how to optimize the adjust the length of the poly(A)-tails generated (see page 2, para. 1-2).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teaching of prior art to modify the composition comprising a complex comprising IVT sgRNA by adding polyA tail of varying length of 5, 10 or 20 adenine nucleotides at 3’-terminal as suggested by Janicke/ Meissner, with a reasonable expectation of success, before the effective filing date of instant invention, to enhance stability and efficiency of sgRNA as suggested by Jinek, Janicke/Meissner (see 133, 134, 386, 387, 426, 444). Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art recognized that 3′-polyadenylation of sgRNA may enhance stability and activity in vivo (see Jinek et al page 5 or Meissner). One of ordinary skill in the art would have been expected to have a reasonable expectation of success in adding polyA tail at 3’terminal of sgRNA because prior art successfully reported polyadenylation at 3’ terminal of RNA as evident from the teaching of Janicke/ Meissner. It should he noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, USPQ2d , slip op. at 20, (Bd, Pat, App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (www.uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Claims 62, 67, 69-70, 119, 129 and 130 are rejected under 35 U.S.C. 103 as being unpatentable over Jinek et al (WO/2013/176772, dated 11/23/2013) as evidenced by Jinek et al (eLife, 2013, e00471, 1-9) and Janicke et al (RNA, 2012, 18:1289–1295, art of record)/ Meissner (US20160348073, EFD 3/27/2015), Epicenter poly(A) polymerase kit, (lit 251, cat.# PAP5104H, 10/2012, 1-5) as applied above for claim 62 and further in view of Kim et al (Nature Biotechnology, 2004, 22, 3, 321-325, IDS) and Church et al (WO2015/013583, EFD 07/26/2013).
The teaching of Jinek and Janicke/Meissner have been described above and relied in same manner here. The combination of references differs from c claimed invention by not teaching that the gRNA molecule lacks a 5' terminal phosphate or a 5’ triphosphate group
Before the effective filing date of instant application, it was generally known that the in vitro–transcribed (IVT) RNAs contain a triphosphate group at the 5′ terminus, which can induce a type I interferon-mediated immune response (Kim et al. 2, 2004, abstract). It is further disclosed that treatment of RNA with calf intestinal phosphatase (CIP) completely removes the 5’triphosphate with complete loss of interferon induction (see Kim 2, page 322, col. 2, para. 3, and figure. 2b). The combination of reference differs from claimed invention by not explicitly disclosing treating sgRNA with phosphatase.
Church et al teach removing phosphate from sgRNA by treating with a phosphatase. It is further disclosed that the genome editing in the cell is carried out with Cas9 by supplementing phosphatase treated gRNA in the tissue culture media. Church et al teach this approach enables scarless genome editing in human stem cells(hiPSC) or P3 primary cells (see example VI) (limitation of claim 67) with up to 50% efficiency with single days of treatment that is 2-10 times more efficient that any past studies. Further, it is also reported that the method significantly lower cellular toxicity (see page 50, lines 6-12, example XVII).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teaching of prior art to modify the composition comprising the complex comprising IVT sgRNA comprising a 3’ polyA tail as disclosed in Jinek and Janicke/Meissner et al by removing 5’-terminal phosphate as disclosed and suggested in Church or Kim, with a reasonable expectation of success, before the effective filing date of instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art recognized that in vitro–transcribed (IVT) RNAs like one disclosed in Jinek contains a triphosphate group at the 5′ terminus that induce a type I interferon-mediated immune response, which is cytotoxic to the cells (see Kim and Church). One of ordinary skill in the art would have been expected to have a reasonable expectation of success in removing 5’ tri-phosphate from sgRNA because prior art successfully reported removing 5’ phosphate as evident from the teaching of Kim and Church. It should he noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, USPQ2d , slip op. at 20, (Bd, Pat, App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (www.uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Claims 62, 88-92, 94 and 95 are rejected under 35 U.S.C. 103 as being unpatentable over Jinek et al (WO/2013/176772, dated 11/23/2013) as evidenced by Jinek et al (eLife, 2013, e00471, 1-9, IDS) and Janicke et al (RNA, 2012, 18:1289–1295, IDS)/ Meissner (US20160348073, EFD 3/27/2015), Epicenter poly(A) polymerase kit, (lit 251, cat.# PAP5104H, 10/2012, 1-5, IDS) as applied above for claim 62 and further in view of Zhang et al (WO2014093712, dated 6/19/2014, IDS)/O’Connell et al (US20180002736, EFD1/28/2015).
The teaching of Jinek and Janicke/Meissner have been described above and relied in same manner here. The combination of references differs from the claimed invention by not teaching that the gRNA molecule contains one or more nucleotides that stabilize the gRNA molecule.
Before the effective filing date of instant application, Zhang teaches single guide RNA for sequence manipulations in cells, which have been chemically modified by incorporating 2'-deoxy or 2'-fluoro analogs (para. 29, 35, 37, 73). Zhang teaches modifying gRNA to improve stability by modifying the nucleotide (page 18, para. 37). It is further disclosed that nucleic acid backbone may be modified, for example, a phosphorothioate backbone (see para. 29) (limitation of claims 88-90, 94 and 95). It is further disclosed that modified bases include, but are not limited to, 2-aminopurine, 5-bromo-uridine, pseudouridine, inosine, 7-methylguanosine (see para. 29, 37) (limitation od claim 92). O’Connell teaches gRNA has one or more base modification or a backbone modification (see para. 619) including modified cytidine or adenosine or guanosine (para. 671, 676).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teaching of prior art to modify the composition comprising sgRNA comprising a 3’ polyA tail as disclosed in Jinek and Janicke/Meissner by modifying the nucleotide as disclosed and suggested in Zhang/ O’Connell, with a reasonable expectation of success, before the effective filing date of instant invention to improve the stability of gRNA. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art recognized that gRNA backbone and/or nucleotide may be modified to improve the stability of gRNA against nuclease degradation (see Zhang). One of ordinary skill in the art would have been expected to have a reasonable expectation of success in modifying the nucleotide base in gRNA because prior art successfully reported modifying gRNA as evident from the teaching of Zhang to improve the stability of gRNA. It should he noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, USPQ2d , slip op. at 20, (Bd, Pat, App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (www.uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Claims 62, 119-122 are rejected under 35 U.S.C. 103 as being unpatentable over Jinek et al (WO/2013/176772, dated 11/23/2013) as evidenced by Jinek et al (eLife, 2013, e00471, 1-9, IDS) and Janicke et al (RNA, 2012, 18:1289–1295, IDS)/ Meissner (US20160348073, EFD 3/27/2015) in view of Epicenter poly(A) polymerase kit, (lit 251, cat.# PAP5104H, 10/2012, 1-5, IDS). as applied above for claim 62 and further in view of Liu et al (EP3842063, dated 06/30/2021, filed on 9/5/2014, EFD9/6/2013).
Claims interpretation: eiCas9 is interpreted as mutating key residues in both DNA cleavage domains of the Cas9 protein (e.g., the D10A and H840A or N863A mutations) resulting in the generation of a catalytically inactive Cas9 (eiCas9 which is also known as dead Cas9 or dCas9) (see specification para. 985, 1315).
The teaching of Jinek and Janicke/Meissner have been described above and relied in same manner here. The combination of references differs from the claimed invention by not teaching that Cas is nickase or dCas9.
Before the effective filing date of instant application, Liu teaches engineering variants of Cas9 that cleave only one DNA strand ("nickases") enable double-stranded breaks to be specified by two distinct gRNA sequences (see para. 60, 65-66) or dCas9 containing inactivating mutations D10A and H840A (para. 23, 24, 67, 126)
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teaching of prior art to modify the composition of Jinek and Janicke/Meissner by substituting Cas9 with nickase or dCas9 c as disclosed and suggested in Liu, with a reasonable expectation of success, before the effective filing date of instant invention to enable double-stranded breaks or enable fusion of dCas9-KRAB. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art recognized that variant of Cas9 for specific use to improve efficiency. One of ordinary skill in the art would have been expected to have a reasonable expectation of success in using variant of Cas9 because prior art successfully reported the use of these Cas9 variants. It should he noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, USPQ2d , slip op. at 20, (Bd, Pat, App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (www.uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
Response to arguments
Applicant reiterate and in part rely on the Examples 14, 15, 16, and 17 of the present application describe the testing of several different polyA tail lengths for guide RNAs, including 10, 20, 50, and 100 adenine nucleotides. Example 14 shows that a Cas9 protein complexed with gRNAs modified to include a 10A or a 20A length tail supported gene editing in primary human hematopoietic stem/progenitor cells and Example 15 demonstrates that RNP complexes comprising either 1OA and 20A templated gRNA were capable of generating significantly modified primary CD4+ T cells at both the PDCD1 and TRBC loci. As shown in, for example, Figures 48A and 48B, compositions comprising gRNA comprising different lengths of polyA tails produced different percentages of edits in target cells. These data indicate the unexpected results that certain polyA tail lengths supported gene editing relative to other polyA tail lengths. None of the cited references, alone or together, teach or suggest the unexpected editing results from compositions comprising a gRNA molecule comprising a targeting domain that is complementary to a target domain from a gene expressed in a eukaryotic cell, wherein the gRNA molecule comprises a 3’ polyA tail consisting of about 10 or about 20 adenine nucleotides; and a nucleic acid encoding a Cas9 molecule, as presently claimed and illustrated by the present application. Applicants’ arguments have been fully considered, but are not found persuasive.
In response, it is noted that claims have been amended to recite composition comprising the gRNA molecule comprises a 3' poly A tail consisting of 10 or 20 adenine nucleotides. It should be noted that any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It should be noted that the ultimate goal of adding polyA tails is to provide stability of gRNA in vivo (see page 5, last para. of Jinek). As previously indicated, Jinek teaches a composition comprising a DNA-targeting RNA polynucleotide (also referred herein as gRNA or, see para. 130) that provides target specificity to the complex by comprising a nucleotide sequence that is complementary to a sequence of a target DNA (see para. 20, 449, 493-494, 517, 533-534, 553, 631 and 567). Jinek further teaches that DNA-targeting RNA (gRNA) may include a 5' cap (e.g., a 7-methylguanylate cap (m7G)) and a 3' polyadenylated tail (i.e., a 3' poly (A) tail) (see para. 133, 134, 386, 387, 426, 444). In view of foregoing, it is clear that Jinek explicitly discloses a composition comprising sgRNA that is 5 capped and 3′-polyadenylated for higher efficiencies of Cas9-mediated genome targeting. A variety of method suitable for this purpose (to introduce 5′-cap or 3′-polyadenylation of varying length including 10A or 15A or 20A) well-known in the art, including one disclosed in Janicke or Meissner. Thus, Janicke//Meissner cure the deficiency in Jinek et al. for adding polyA tails to provide stability of gRNA in vivo. To the extent that Janicke et al and/or Church describe adding polyA tail and/or 5’cap to the gRNA to mimic mRNA structure to stability of gRNA in vivo, the rejection is applicable to the instant case. The fact that 3’polyA may be added to the RNA to provide stability of gRNA to a greater extent is an expected result, and is the goal behind adding 3’ poly A tail. As indicated in MPEP 716.02(c), Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). Further, unexpected results have to be commensurate with the scope of the invention. "Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)."
Further, Unexpected results have to be commensurate with the scope of the invention. "Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)."
As stated in previous office action examples 14 teaches cord blood CD34+ HSC were electroporated with Cas9 RNP complexed with HBB-8 with defined gRNA with engineered polyA tails of defined length (10A, 20A or 50A). The results indicate that D10A Cas9 protein complexed to gRNAs modified to include a 5' cap and 3' polyA tail of specific length (10A or 20A) supported gene editing in primary human hematopoietic stem/progenitor cells (Fig. 45C) (see page 378).
In the instant case, the independent claims are not limited to D10A Cas9 protein complexed to gRNAs modified to include a 5' cap and 3' polyA tail.
Likewise, the specification further teaches an ARCA-capped gRNAs with a polyA tail of 10 or 20 were capable of generating significantly modified primary CD4+ T cells at both the PDCDI and TRBC locus (Fig. 46B and Fig. 47B). In view of foregoing, it is unclear if the same unexpected result could be extended in other cells type and gRNA comprising any other targeting domain and gRNAs that has only 3' modified polyA tail with 10A or 20A tail as recited in the claim. In fact, a post filing publication summarized by the teaching of Mu (Protein Cell 2019, 10(3):223–228, cited as evidence without relying on rejection) teaches 5’capped and 3’polyA tailed sgRNA (CTsgRNA) enhance the efficiency of CRISPR-Cas system. Mu reported that “ neither 5′ cap nor the 3′ polyA tail modification alone was able to induce indels more efficiently than unmodified sgRNAs in primary T-cells (Fig. 1D). Similar results were obtained at the HBB loci (see Mu Fig. 1E). Taken together, these results showed that the CT (5’capped and 3’polyA tailed sgRNA ) modification enhanced sgRNA intracellular stability, improved genome editing efficiency in K562 and human primary T cells” (see page 225, col. 1, para. 1). This post filing publication explicitly teaches that necessity and criticality of both 5’and 3’sgRNA modification to induce indels in specific cell type (primary T cells). The claims are not so limited.
In response to applicant’s argument that unexpected results are obtained with only certain (10A or 20A) polyA tail lengths that supported gene editing relative to other polyA tail lengths (figure 48A or 48B), it is noted that Example 16 again teaches all gRNAs differentially modified at the 3' end, each gRNA that are in vitro transcribed and modified at the 5' end with an ARCA cap which was added during the in vitro transcription process. The claims are not so limited. The modification is expected to ensure the gRNA is functional and stable. DNA sequencing analysis indicated that the optimal polyA tail length was 20As (see page 380).
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The figure 48B of the instant application clearly shows there is no significant difference between percentage indel observed with polyA tail length of 2A, 10A, 15A or 25A. It is unclear from the figure whether level of gene editing is affected by cell type, length of the targeting domain or something else. The specification describes that the targeting domain comprises 10+/- to 100+/-5 nucleotides in length. In some embodiment, the targeting domain comprises a secondary domain and a core domain (see page 32, lines 18-19). Figure 48A results with polyA tail of 10A and 20A that is strikingly different from percentage indel observed in figure 48B. These results show an inconsistent pattern and it is unclear if the results observed with polyA with 10A or 20A could be extended to all other human cell type, gRNA of varying length with a polyA tail without an ARCA cap at 5’ end of gRNA, or gRNA comprising any other targeting domain of varying length.
Applicant is invited to provide clarification and/or rebuttal for the inconsistent variable results observed with gRNA as discussed above.
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants’ arguments are not compelling and do not overcome the rejection of record.
Examiner’s note: Applicant’s representative is requested to contact Examiner to resolve the pending issues to put instant application in condition for allowance.
Obviousness type Double Patenting
Claims 62, 67, 69-70, 88, 94-95, 120-122, 129 and 130 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 162, 387-393, 396, 398-400, 403, 407-409, 417-419 of copending Application No. 16098845 in view of Janicke et al (RNA, 2012, 18:1289–1295, IDS) and Church et al (WO2015/013583)/ Zhang et al (WO2014093712) for the reasons of record.
In the instant case, even though the conflicting claims are not the same, they are not patentably distinct from each other because both sets of claims encompass overlapping subject matter directed to a gRNA molecule comprising a 3’ polyA-tail. Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teaching of prior of ‘845 to modify the method of using composition comprising sgRNA by adding polyA tail of varying length from 10 to 20 adenine nucleotides at 3’-terminal using method as disclosed in Janicke and remove 5’-terminal phosphate as disclosed and suggested in Church, with a reasonable expectation of success, before the effective filing date of instant invention, to enhance stability and efficiency of sgRNA as suggested by ‘845. This is a provisional nonstatutory double patenting rejection.
Response to arguments
While Applicant has requested that the rejection be held in abeyance until allowable subject matter can be identified, a request of abeyance does not overcome or address an issue of obvious double patenting between claims in the instant case and application 16098845. Thus, the rejection is maintained.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANOOP K SINGH/Primary Examiner, Art Unit 1632