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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 9, 2026 has been entered.
Application Status and Withdrawn Rejections
Applicant’s amendments filed January 9, 2026, amending claims 7 and 23 is acknowledged.
Claims 1, 3, 5, 7, 10-11, 16-21, 23 and 25 are pending and under examination.
The amendments to claims 7 and 23 overcome the §112(b) rejection. The rejection is withdrawn.
The § 103 rejections over Zhang in view of Liu and Shi are withdrawn in favor of a new rejection over the same references and an additional prior art rejection to further address Applicant’s arguments regarding the obviousness of optimizing the arrangement of NLS sequence.
The Wolfe Declaration filed under 37 CFR § 1.132 on January 9, 2026 has been thoroughly considered. Examiner’s response to the evidence in the Declaration and to Applicant’s remarks as they pertain to the rejected claims over prior art is after the § 103 rejections.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 103
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.
Claims 1, 3, 5, 10-11, 16-21, 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Liu et al., Nucleic Acids Research (2019), 47: 4169-4180; published March 20, 2019, of record), in view of Zhang (WO 2018035388 A1, published February 22, 2018, of record), Shi (US 20230002756 A1, priority to and fully supported in provisional application 62/947479, filed December 12, 2019, of record) and Zhang2 (CN 107012164 A, published August 4, 2017, English translation attached).
Regarding claim 1, Liu teaches optimizing the structure of an NLS-Cas12a fusion protein for gene editing in mammalian cells and zebrafish (Title, Abstract). Liu teaches AsCas12a, LbCas12a, and FnoCas12a fusion proteins with the SV40 nuclear localization signal (NLS) sequence alone or in combination with the nucleoplasmin (NLP) NLSs fused at the Cas12a N-terminus and C-terminus for gene editing in HEK293 T-cells (Figure 1). Liu teaches using two different NLS sequences, one of which is the nucleoplasmin NLS, fused at the C-terminus of Cas12a increases gene editing in HEK293T cells compared to a single NLS sequence (Figure 1C-D). Liu teaches altering the NLS composition of the Cas12a fusion protein compared to previous studies for use in editing in Zebrafish (page 4176, ¶1).
Liu does not teach a Cas12a with a c-myc NLS.
Zhang illustrates a fusion protein comprising AsCpf1 (i.e., a Cas12a protein) fused to an NLS at the N-terminus (Fig 4a). Zhang also teaches that Cpf1 proteins can be fused to 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 NLS sequences at the C-terminus, fused to 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 NLS sequences at the N-terminus, or a combination of these ([0184]). Zhang teaches the NLSs can be the c-Myc NLS sequence PAAKRVKLD and the nucleoplasmin NLS sequence KRPAATKKAGQAKKKK ([0184]). Zhang teaches the need to optimize CRISPR-Cas based systems used in therapy for high specificity and high efficacy ([0287]). Zhang teaches such optimization includes “selecting one or more CRISPR-Cas system functionality and optimization of selected parameters or variables associated with the CRISPR-Cas system and/or its functionality” ([0288]). Zhang teaches one area of optimization is “ability of effector protein to access regions of high chromatin accessibility” and “CRISPR effector spatiotemporal expression” ([0294]).
Shi teaches AsCas12a fused to 6 copies of an c-Myc NLS at the C-terminus (Fig 1; [0176]). Shi teaches AsCas12a has two potential nuclear export signals in the highly conserved RuvC domain, which could account for low editing efficiency compared to Cas9 ([0196]). Shi teaches “optimization of an AsCas12a system to improve knockout efficiency in mammalian cells” (Fig 1A-E; [0050]). Shi teaches that additional copies of the c-myc NLS attached to Cas12a enhanced editing efficiency ([0197]).
Zhang2 teaches Cpf1/Cas12a-mediated genome modification in plants (Abstract). Zhang2 teaches NLS coding sequences can be attached at the 5’ end and/or the 3’ end of the coding sequence (i.e., the N-terminus or the C-terminus of the protein) (page 2, ¶11). Zhang2 teaches “Preferably, the NLS is at least one of… nucleoplasmin NLS, c-myc NLS…” (page 2, ¶12). Zhang2 teaches “Commonly used NLS available in this field are SV40 NLS, nucleoplasmin NLS, c-Myc NLS…” (page 4, ¶13).
Regarding claims 1, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have additionally included c-myc NLS sequences taught in Zhang1, Shi and Zhang2 to the C-terminus of Liu’s Cas12a protein comprising the SV40 NLS and nucleoplasmin (NLP) NLS at the C-terminus to generate a Cas12a-NLS(NLP)-NLS(myc)-SV40(NLS) fusion protein. It would have amounted to the simple combination of protein domains fused in known ways to yield predictable results. The skilled artisan would have predicted that the c-myc NLS could be attached to the C-terminus along with the a NLP NLS because 1) Liu teaches two NLSs fused to the C-terminus, one of which is the NLP NLS, 2) Shi demonstrates fusion of 1, 2, 4 and 6 c-myc NLSs to the C-terminus, 3) Zhang teaches that multiple NLS sequences can be placed at the C- termini of Cas12a including the c-myc and NLP NLSs, and 4) Zhang2 teaches that NLP and C-myc NLSs are “commonly used” and “available” in the field. It is noted that claims 1, 3, 5, 7, 10 and 11 are directed to products, and therefore the only predictability required is the ability to produce the protein in vitro or in vivo systems. Because Zhang2 teaches the NLSs are “commonly used”, it was entirely predictable that the fusion proteins could be produced in vitro or in vivo. The skilled artisan would have been motivated to do so to optimize the structure of the Cas12a-NLS fusions as taught in Liu, Shi and Zhang for its intended functionality, and because Zhang suggests adding c-myc and nucleoplasmin NLSs at the C- terminus. It is clear from Liu, Zhang, Shi and Zhang2 that optimization of the Cas12a nuclease for use in different systems, including the NLSs attached to it for nuclear localization, is routine in the art when used for gene editing purposes in eukaryotic cells.
Regarding claims 3 and 11, it would have been obvious to the skilled artisan to have included a second and/or third c-Myc NLS at the N-terminus of the Cas12a-NLS(NLP)-NLS(myc)-SV40(NLS) fusion protein rendered obvious for claim 1. It would have merely amounted to duplication of a known NLS sequence and fusion at known locations on a Cas12a protein. It was entirely predictable that a fusion protein with at least 4 or 5 NLSs, one or two of which is fused to the N-terminus could be produced in vitro or in vivo because 1) Zhang teaches that up to 10 NLSs NLS sequences can be placed at the N- termini of Cas12a including the c-myc, 2) Shi demonstrates up to six tandem c-myc NLS fused to Cas12a. and 2) Zhang2 teaches that c-Myc NLSs are “commonly used” and can be attached at the N-terminus. The skilled artisan would have been motivated to do so to optimize the structure of the Cas12a-NLS fusions as taught in Liu, Shi and Zhang for its intended functionality, and because Zhang suggests adding c-myc and NPL NLSs at the N- terminus. It is clear from Liu, Zhang, Shi and Zhang2 that optimization of the Cas12a nuclease for use in different systems, including the NLSs attached to it for nuclear localization, is routine in the art when used for gene editing purposes in eukaryotic cells.
Regarding claim 5, Zhang teaches AsCpf1 is a Cas12a from Acidaminococcus sp. (page 530).
Regarding claim 10, it would have also been obvious to one skilled in the art to have additionally included at least two c-myc NLSs at the C-terminus of Cas12a. It would have been entirely predictable that an additional c-myc could be added to the C-terminus of the Cas12a-NLS(NLP)-NLS(myc)-SV40(NLS) fusion protein rendered obvious above because Zhang teaches that up to 10 NLSs can be fused to Cas12a, including the c-myc NLS, and Shi demonstrates up to six c-myc NLS at the C-terminus of Cas12a.
Regarding claims 16-17, the obviousness of fusing both a c-Myc and a nucleoplasmin NLS to the C-terminus of Cas12a is recited above in paragraph 17. Liu also teaches producing Cas12a/crRNA ribonucleoproteins for the purpose of injecting them into zebrafish embryos for genome editing (age 4172, ¶5-6). Liu teaches Cas12a has been used successfully to restore dystrophin function via targeted gene correction in embryos of a mouse model of Duchenne muscular dystrophy (DMD) (i.e., in a patient) or by exon skipping via the generation of segmental deletions in an DMD-iPSC line… [and] facilitate targeted cytosine base editing within the genome. Together, these results demonstrate that Cas12a-based systems have the potential to facilitate a broad variety of genome editing goals with both research and therapeutic applications.” (page 4170, ¶1). Zhang also teaches providing NLS-tagged Cas12a in a pharmaceutical composition to a patient for the purpose of treating the patient with a genetic disease caused by a mutation in a genetic locus (i.e., a gene) ([0839]-[0841]).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have administered the obvious Cas12a-NLS(NLP)-NLS(myc)-SV40(NLS) fusion protein in a method for treating or otherwise alleviating symptoms of a genetic disease. It would have merely amounted to using the obvious fusion protein in methods for which Cas12a proteins are known to function. The skilled artisan would have predicted that the Cas12a-NLS(NLP)-NLS(myc)-SV40(NLS) protein could be delivered to patients because Liu demonstrates a nearly identical fusion protein – only missing the nine amino acids of the c-myc NLS – can be delivered to an animal model, and additionally teaches Cas12a should be able to be used in a therapeutic applications. The skilled artisan would have been motivated to use administer the obvious Cas12a-NLS(NLP)-NLS(myc)-SV40(NLS) to a patient for therapeutic purposes because Liu and Zhang suggests using Cas12a effectors in therapeutic applications.
Regarding claims 18 and 21, Zhang teaches a mutation can be repaired with an exogenous template polynucleotide wherein said repair results in a mutation comprises a deletion (i.e., mutated gene inactivation) ([0209], [0896]).
Regarding claims 19-20, Zhang teaches editing can include repairing a mutant allele into a wild type allele (i.e., repairing gene function) ([0903]).
Regarding claim 23, the obviousness of adding a c-myc NLS to the N-terminus of Cas12a and a c-myc and nucleoplasmin NLSs to the C-terminus of Cas12a is recited above in paragraph 18.
Regarding claim 25, as indicated above for claim 5, Zhang teaches AsCpf1 is a Cas12a from Acidaminococcus sp. (page 530).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Liu (Liu et al., Nucleic Acids Research (2019), 47: 4169-4180; published March 20, 2019, of record), Zhang (WO 2018035388 A1, published February 22, 2018, of record), Shi (US 20230002756 A1, priority to and fully supported in provisional application 62/947479, filed December 12, 2019, of record) and Zhang2 (CN 107012164 A, published August 4, 2017, English translation attached), as applied to claims 1, 3, 5, 10-11, 16-21, 23 and 25 above and further in view of Behlke (US 20180187176 A1, published July 5, 2018).
The teachings of Liu, Zhang, Shi and Zhang2 are recited above and applied as for claims 1, 3, 5, 10-11, 16-21, 23 and 25 above.
Liu, Zhang, Shi and Zhang2 do not teach Cas12a proteins fused to a bipartite (BP) SV40 NLS.
Behlke teaches AsCpf1 and LbCpf1 (i.e., AsCas12a and LbCas12a) polypeptides for use as endonuclease systems for mammalian cells lines (Abstract). Behlke teaches testing various NLS sequences fused to AsCas12a in cell lines ([0045]). Behlke teaches “the nucleoplasmin functions best in mammalian cells while the SV40 NLS appears to function in almost any nucleated cells. The bipartite SV40 (i.e., BP SV40) NLS is functional in both Cas9 and Cpf1. Having two different NLS domains may expand effectiveness across a broad spectrum of species” ([0045]).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have substituted the SV40 NLS in the Cas12a-NLS(NLP)-NLS(myc) rendered obvious above for claim 1 with the BP SV40 NLS taught in Behlke. It would have amounted to the simple substitution of one known NLS for another known to be functional when attached to a Cas12a protein. It was entirely predictable that the substitution for the monopartite SV40 NLS for a bipartite SV40 NLS could be made and result in a functional Cas12a protein because Behlke teaches BP SV40 is functional when fused to Cas12 nucleases. Because the prior art recognizes the equivalence of the SV40 and bipartite SV40 for the purpose of nuclear localization of Cas12a in eukaryotic cells, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP 2144.06.II. Nevertheless, the skilled artisan would have been motivated to make the substitution for the purpose of optimizing the structure of the Cas12a-NLS fusions as taught in Liu, Shi and Zhang for its intended functionality. It is clear from Liu, Zhang, Shi, Zhang2 and Behlke that optimization of the Cas12a nuclease for use in different systems, including the NLSs attached to it for nuclear localization, is routine in the art when used for gene editing purposes in eukaryotic cells.
Response to Arguments and Declaration
Applicant’s arguments regarding the obviousness rejection (Remarks, pages 6-15) are directed to the withdrawn rejections are therefore moot. However, as the new rejection is similar to the withdrawn rejections, the arguments and evidence presented in the Declaration are addressed below as they pertain to the current rejections.
Applicant states the requirements for a prima facie case of obviousness, stressing that all the claimed elements must have been known in the prior art, the skilled artisan could have combined the elements by known methods with no change in their respective functions, and the combination yielded nothing more than predictive results (pages 6-7). Applicant then argues that there is no finding that the prior art included each element claimed (page 7, last ¶). This argument has been fully considered but is not persuasive because each of the claimed elements – a Cas12a protein, a c-myc NLS, a nucleoplasmin NLS, and the fusion locations (N- and C- terminus) – were all known and taught in the prior art as evidenced by Zhang, Zhang2, Shi, Lui and Behlke cited in the rejection above.
Applicant first argues that there is no reasonable expectation of success because 1) Zhang’s disclosure of NLS type and number is generic and vague without giving guidance on how to choose the specific arrangement (pages 9-10) and cites to Applicant’s evidence for guidance on how to choose the specific type and location of the NLS (page 11). This argument and cited evidence in the Specification has been fully considered, but are not persuasive.
First, Applicant’s cited evidence that the position of the NLS in the fusion protein, in addition to the NLS type, affects Cas12a editing efficiency, was already shown in Liu. Liu varies the position of NLP and SV40 NLSs attached to Cas12a and discovers different editing efficiencies. Second, Applicant’s demonstration that empirical testing is needed to validate a specific NLS arrangement is not persuasive to overcome obviousness. Each of the cited references make clear that NLS type/position must be optimized (i.e., empirical testing), thus it would have been obvious to make different NLS type/position combinations of NLS sequences that are “Commonly used [and] available in [the] field” (Zhang2, page 4, ¶13).
Applicant also cites to evidence that “N-terminal c-Myc positions… do not work well.” (page 11, ¶2). This evidence is confusing in light of the claimed fusion proteins of claims 3 and 11 which recite at least one c-Myc NLS at the N-terminus. It appears that Applicant is trying to argue that claims 3 and 11 are not enabled for a predictable use.
Applicant argues that the combination of the NLP and c-myc NLS “was superior to NLP NLS alone which is not taught or suggested in Zhang” (page 11, ¶3). This argument and evidence are not persuasive since it relies on features that are not recited in the rejected claims – specifically a minimum editing efficiency in a specific cell type. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Again, it is noted that at least for claims 1, 3, 5, 7 and 10-11, the only predictability needed is that the protein can be designed and produced. The fusion protein is not claimed in a composition with specific cell types and there are no functional requirements for the claimed protein in terms of editing or cellular localization efficiency.
Applicant argues that Liu and Shi fail to provide the predictability that is lacking in Zhang because Liu does not demonstrate substitution of C-myc NLS for SV40 NLS and Shi is limited to using c-Myc alone (pages 12, ¶2). Applicant cites to ¶4 of the Wolfe Declaration that “Liu did not believe that the localization activity of the SV40 NLS can be expected to predict the localization activity of the NLP NLS. This argument and evidence are moot because the current rejection renders obvious the addition of c-myc NLS to Liu’s SV40(NLS)-NPL(NLS) Cas12a fusion protein. Nevertheless, taking the totality of the cited references, it is evident that 1) all the claimed NLS types were “commonly used” and “available” in the art, 2) the most common positions for NLSs are the N- and C-terminus of proteins, and 3) optimization of NLS type and placement on a Cas12a protein was routine in the art and necessary for different systems.
Applicant argues that NLS substitutions are not generally known in the art. Applicant cites to ¶3-7 of the Declaration for evidence that NLS substitutions are not generally known (pages 12-14). Although the current rejection relies on the addition of a c-Myc NLS to Liu’s fusion protein, in view of Applicant’s preferred embodiments and the rejection of claim 7 which relies on a substitution of the monopartite SV40 NLS with a bipartite SV40 NLS, Applicant’s arguments and proffered evidence are addressed here.
Applicant argues that Liu shows that a bipartite NLP NLS and the SV40 NLS do not have equivalent activities while Shi only shows multiple copies of a one NLS (page 13, ¶1-2; Declaration ¶4). This argument has been fully considered but is not persuasive because the claims merely require the appendage of the NLS to Cas12a. The claims do not recite a specific level of localization or editing efficiency. Because Liu demonstrates Cas12a with an NLP NLS, Shi demonstrates a Cas12a with a C-myc NLS, and Zhang2 teaches each are commonly used in the field of gene editing, it would have been entirely predictable that they could be added individually or together and in place of one another.
Applicant argues that others in the art have concluded that NLS species cannot be predictable substituted for one another. Applicant cites Chai et al., as explaining that different NLS classes can have vastly different biochemical requirements for import into the nuclei. Chai specifically teaches that a bipartite NLS from MxB, uses different means to gain access to the nucleus (page 13, last ¶ through page 14, ¶3; Declaration ¶5). This argument and proffered evidence have been thoroughly considered, but are not persuasive. First, the evidence is directed to an unclaimed NLS – namely an NLS sequence from MxB. To Examiner’s knowledge, the MxB NLS has not been used for nuclear localization of CRIPSR endonucleases. However, each of the claimed NLSs have been cited as being “commonly used” and “available” for fusion to Cas12a proteins. Additionally, Liu teaches including both a monopartite and a bipartite NLS to the C-terminus of Cas12a. Thus, Chai does not appear to be relevant to whether it would been obvious to substitute the c-Myc NLS, a monopartite NLS, for the SV40 NLS, another monopartite NLS, which was included in the rationale in the previous office action.
Applicant argues that the a CRISPR Journal publication in 2025 studied the impact of the SV40 and c-Myc NLS in different combination and numbers with the NLP on the activity of a different CRISPR nuclease, Cas9. Applicant and the Declaration note that the study showed that increasing the number of NLSs on proteins can have detrimental effects on the solubility of the protein – specifically using 6x SV40 NLS copies. Applicant concludes that based on this post-filing evidence, the presently claimed embodiments were unpredictable in 2020, the effective filing year of the claimed invention (page 14, last ¶; Declaration ¶6). Applicant’s argument and the proffered evidence have been fully considered but are not persuasive. First, the cited Noel reference was published 5 years after the effective filing date of the claimed invention. Therefore, it was not available to the skilled artisan by the effective filing date when considering the number and type of NLS sequences to append to Cas12a. Second, at least for claims 1, 3, 5, 7 and 10-11, there is no requirement for in vitro purification of the Cas12a protein from E. coli cells. The claims also encompass the fusion proteins expressed in the eukaryotic cells of interest, for example HEK293 cells, and in eukaryotic recombinant protein production cells lines, such as Sf9 insect cells. Because Zhang, Liu, Zhang2 and Shi all teach either in vitro purification or in vivo expression of Cas12a with 2-6 NLS sequences, the skilled artisan would have predicted that a Cas12a with an NLP and one, two or three c-Myc NLSs could be produced in some manner. Finally, if Noel was available as prior art, taken as a whole the addition of c-Myc, NLP and SV40 NLSs would have been obvious because Noel teaches Cas9 with a single SV40, a single c-Myc and a single NLP NLS (t-Cas9) had the highest yield of all multiple-NLS Cas9 constructs when expressed in E. coli (see FIG. 2 of cited Noel et al., reference). Additionally, as long as the NLSs comprise at least 2 different sequences, the addition of up to five NLSs do not appear to be detrimental to purifying the Cas12a proteins form E. coli (FIG 2). The claims do not recite more than one SV40, nor do the claims recite 6 copies of the same or different NLSs. As such, the Noel reference does not specifically address the previous obviousness rejections or the current rejections, and do not have sufficient nexus to the claimed fusion proteins.
Applicant argues that the references fail to properly combine all the claimed elements because of Zhang’s generic disclosure, 2) Liu never pairs the NLP NLS with another other NLS and fails to address substitutability requirements, 3) Shi is limited to multiple c-Myc NLSs, and 4) Examiner has ignored whether there is reasonable expectation of success for NLS pairings at the C-terminus (pages 15, ¶1-2). This argument has been fully considered, but is not persuasive for reasons already given. Briefly, considering the totality of the cited references, it is evident that 1) all claimed NLS types were “commonly used” and “available” in the art, 2) the most common positions for NLSs are the N- and C-terminus of proteins, and 3) optimization of NLS type and placement on a Cas12a protein was routine in the art and necessary for different systems. Regarding, the obviousness of optimizing the type/position of the NLS, the prior art is flush with examples of researchers trying different NLS combinations to find the optimal combination for specific CRISPR nucleases in specific systems. For instance, Koblan et al., teaches optimizing NLS motifs in Cas9-based base editors (Nature Biotechnology (2018), 36: 843-846; Fig 1d). Hu teaches optimization of position and type of NLS fused to Cas9 when delivered to Zebrafish as either an RNP or mRNA (Genes, Genomes, Genetics (2018), 9: 823-831; Fig 1). Shi et al., teaches the need to optimize NLS-Cas9 design for expression in filamentous fungi (Appl Microbiol Biotechnol (2017), 101: 7435-7433; page 7437, ¶1). Sternberg and Klompe teaches optimization of the NLS position design when expressing components of the CRISPR-Tn7 Vibrio system (US 20200283769 A1; [0124]). A Master’s Thesis by Pan expressly teaches “we need to optimize the system before we can use it in animal or plants, such as codon optimization and NLS addition.” (Qianli Pan, Application of CRISPR/Cas9 to edit genes affecting seed morphology traits in wheat, 2019, Kansas State University). Thus, it was widely understood that the NLS design on CRISPR endonucleases would need to optimized for specific systems using known NLSs in the art, which Zhang and Zhang2 teaches including nucleoplasmin and c-Myc NLS at either the N- or C-terminus. Finally, it was noted several times that the only predictability in the art required for the product claims is their ability to be produced. Because the claims recite merely known NLS sequences, each of which was known to be amendable to attachment to Cas12a and be expressed in cells, the skilled artisan would conclude that, more likely than not, the claimed combination could also be appended to Cas12a for successfully production in cells.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE KONOPKA whose telephone number is (571)272-0330. The examiner can normally be reached Mon - Fri 7- 4.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571)272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635