DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/24/2025 has been entered.
Claims 1-8, 10, 12, 14, 16, 18-21, 25, 27 and 30 are pending in this application.
Applicant’s amendment to the claims filed 12/24/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 12/24/2025 in response to the final rejection mailed on 07/11/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, corresponding to claims 1-8, 10, 12, 14, 16, 18, 25 and 27, drawn to the technical feature of a composition comprising an embryonic ectoderm development (EED) polypeptide binder (EB) domain and a Cas9 domain linked to the EB domain, a pharmaceutical composition and a kit,
Species A11) the EB domain comprises the amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%,80%, 85%, 90%,91%, 92%,93%,94%,95%, 96%,97%, 98%, or 100% identical along to the amino acid sequence of SEQ ID NO: 13,
Species B1) the amino acid linker comprises a sequence that may include, but is not limited to, a sequence having the amino acid sequence from SEQ ID NO: 14,
Species C6) the Cas9 domain comprises the amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%,80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% identical to the amino acid sequence of SEQ ID NO: 44, and
Species D1) the polypeptide comprises the amino acid sequence at least 50%, 55%,60%, 65%, 70%, 75%,80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 100% identical to the amino acid sequence of SEQ ID NO:37,
elected without traverse in the reply filed 08/30/2024.
Claims 19-21 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/30/2024.
The amended claims filed 12/24/2025 no longer recite the species of group C regarding the sequence of the Cas9 domain, and instead recite “the Cas9 domain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 34” in claim 1. In view of this amendment, the requirement for election of species among the species of group C no longer applies.
Claims 1-8, 10, 12, 14, 16, 18, 25 and 27 are being examined on the merits only to the extent they read on the elected subject matter.
Claim Objections
The objection to claim 8 is withdrawn in view of the amendment to recite “wherein the amino acid linker comprises the amino acid sequence of any one of SEQ ID NOs: 14-33”.
Claim Rejections - 35 USC § 112(b)
The rejection of claim 7 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention is withdrawn in view of the amendment to claim 7 to recite “wherein residues 47 and 54 of SEQ ID NO: 13 are not modified”.
Claim 27 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 27 is indefinite for the phrase “a kit comprising (a) the composition of claim 1 and (b) a control composition comprising the composition of claim 1, having an inactive EB domain that instead does not bind to EED”. As the claim recites no structural limitations on the EB domain recited in part (b), and part (b) requires the composition of claim 1, it is unclear whether the EB domain recited in part (b) is the same as the EB domain recited in the composition of claim 1, or whether the EB domain of part (b) is distinct from the EB domain of the composition of claim 1, or whether the EB domain of part (b) is added to the composition of claim 1 such that the control composition contains more than one EB domain.
Response to Remarks: beginning on page 6 of Applicant’s response to rejections under 35 USC 112(b); Applicant in summary contends the amendment to claim 27 obviate the previous 112(b) rejections.
Applicant’s remarks are considered and found not convincing.
While Applicant has amended the claim to recite “(b) a control composition comprising the composition of claim 1, having an inactive EB domain that instead does not bind to EED”, Applicant has not clarified whether the EB domains recited in parts (a) and (b) are the same EB domain or are distinct EB domains, or whether the part (b) contains multiple EB domains. As there are no structural limitations recited for the EB domain of part (b), it is unclear whether the inactivity of the EB domain of part (b) is due to a structural difference from the EB domain of part (a), or an effect on the EB domain resulting from a component from the control composition. The amendment to claim 27 limits that the control composition comprises an EB domain that is inactive, but does not exclude the addition of a second EB domain to the composition of claim 1, and does not exclude that the EB domain of part (b) is structurally identical to the EB domain of the composition of claim 1.
Claim Rejections - 35 USC § 103
Claims 1-7, 10, 16 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Ann Rev Biochem, 2016, 85:227; cited on the IDS submitted 08/30/2021; herein referred to as Wang), Moody et al. (PNAS, 2017, 114:10125; cited on the IDS filed 07/28/2022; herein referred to as Moody), and UniProt Accession No. A0A386IRG9_STAAU (1 page, 12/05/2018; cited on the Form PTO-892 mailed 07/11/2025; herein referred to as UNI1), and evidentiary reference GenPept Accession No. 5WP3_B (2 pages, 01/15/2018; cited on the Form PTO-892 mailed 12/23/2024; herein referred to as MOODY2).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 1 is drawn to a composition comprising an embryonic ectoderm development (EED) polypeptide binder domain (EB) comprising at least 95% sequence identity with SEQ ID NO: 13, and a CRISPR associated protein 9 (Cas9) comprising at least 95% sequence identity with SEQ ID NO: 34 that is linked to the EB domain.
Wang discusses CRISPR/Cas9 genome editing [title] and discloses applications of Cas9 for genome editing, regulation, and imaging [abstract].
Regarding claim 1 and the Cas9 domain, Wang teaches that sequence-specific DNA-binding proteins such as Cas can recruit epigenetic modifiers to reshape the epigenome at a given locus [p 242, para 4], and describes an epigenome editing application comprising a fusion of deactivated Cas9 (dCas9) with the transcriptional repressor domain KRAB [Figure 2a and legend] to induce site-specific epigenome editing via methylation of histone H3K9 to suppress expression of globin genes [p 242, para 4]. Put another way, Wang teaches the use of a Cas9 fusion to localize to a specific sequence in the genome in order to facilitate the activity of its fusion partner, KRAB, with said targeted area of the genome, resulting in site-specific epigenetic regulation.
Wang does not teach an EB domain, or a Cas9 domain with the sequence limitations recited in the claim.
Moody discusses the polycomb repressive complex (PRC2) histone methyltransferase and its role in epigenetic regulation, and discloses that disrupting PRC2 function can be blocked by disrupting the interaction of the domains EZH2 and EED of PRC2 [abstract].
Regarding claim 1 and the EB domain, Moody teaches an EB domain EB22 that has the highest affinity for binding EED of PRC2 [p 10126, col 1, para 2], wherein said binding is understood to affect the histone methyltransferase activity of PRC2 and thereby affect epigenetic regulation. Moody further teaches EB22 contains the motif FAANRALI as evidenced by MOODY2, wherein X1 is A, and X3 is L, and wherein the peptide shares 98.2% sequence identity with SEQ ID NO: 13 [see Appendix A].
UNI1 discloses a dCas9 protein from Staphylococcus aureus [lns 5-7].
Regarding claim 1 and the sequence limitations of the Cas9 domain, UNI1 discloses the dCas9 protein from Staphylococcus aureus that is 100% identical to SEQ ID NO: 34 [see Appendix B].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Wang, Moody and UNI1 to modify the fusion of Wang by using the EB of Moody and the Cas9 of UNI1 to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the fusion of Wang by using the EB domain of Moody, because Wang teaches that that sequence-specific DNA-binding proteins such as Cas can recruit epigenetic modifiers to reshape the epigenome at a given locus and Moody teaches a method wherein an EB domain can affect epigenetic regulation by affecting PRC2 histone methyltransferase activity. One of ordinary skill in the art would have had a reasonable expectation of success because Wang discusses a method of site-specific epigenetic regulation using Cas9 fusions with peptide domains that affect histone methylation, and Moody discusses methods of epigenetic regulation involving peptide domains that affect enzymes responsible for histone methylation.
One of ordinary skill in the art would have recognized that both the dCas9 of Wang and the dCas9 of UNI1 are dCas9 proteins, and as such both are capable of being incorporated into such fusions as described by Wang. Thus it would have been obvious to one of ordinary skill in the art to replace the dCas9 of Wang with the dCas9 of UNI1 arrive at the claimed invention, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both Wang and UNI1 disclose dCas9 proteins.
Regarding claim 2, Wang teaches a fusion of dCas9 with the epigenetic modulator KRAB [Figure 2b], and Moody teaches the EB domain EB22 [p 10126, col 1, para 2] as discussed in the rejection above. In the drawing of the dCas9 in [Figure 2b] of Wang, a gray bar is depicted separating dCas9 from KRAB, which is interpreted to correspond to a linker separating the two elements of the fusion protein.
Regarding claims 3-7, Moody teaches the EB domain of EB22 [p 10126, col 1, para 2] that contains the motif FAANRALI as evidenced by MOODY2, wherein X1 is A, and X3 is L, and wherein the peptide shares 98.2% sequence identity with SEQ ID NO: 13 [see Appendix A]. Regarding the limitation of claim 7 that residues 47 and 54 are unmodified, the EB22 peptide as shown in the alignment of [Appendix A] is identical to SEQ ID NO: 13 through residue 60, and therefore EB22 is considered to be unmodified at residues 47 and 54.
Regarding claim 10, UNI1 discloses the dCas9 protein from Staphylococcus aureus that is 100% identical to SEQ ID NO: 34 [see Appendix B].
Regarding claim 16, as described in the rejections above, Wang teaches a fusion of a Cas9 [Figure 2a and legend], Moody teaches the EB22 polypeptide [p 10126, col 1, para 2] that shares 98.2% sequence identity with SEQ ID NO: 13 [see Appendix A], and UNI1 teaches a Cas9 that shares 100% sequence identity with SEQ ID NO: 34 [see Appendix B]. As such, the combined fusion of the Cas9 of UNI1 with the EB domain of Moody would share 97.1% sequence identity (and 97.7% local similarity) with SEQ ID NO: 37 if the EB domain were at the N-terminus [see Appendix C].
Regarding the limitations of claim 27 part (a), Wang, Moody and UNI1 teach the combined fusion of a Cas9 with EB22 as discussed in the rejections above.
Regarding the limitations of claim 27 part (b), Moody additionally teaches the variant EB22.2NC that is incapable of binding soluble EED that is used as a negative control [p 10126, col 2, para 2], therein satisfying the limitation of an inactive EB domain. In light of the combined teachings of Wang, Moody and UNI1, it would have been obvious for one of skill in the art to combine the disclosed reagents as a kit, as it is routine in the art to optimize methods for reproducibility of results that would include the incorporation of necessary reagents into a kit.
Therefore, the invention of claims 1-7, 10, 16 and 27 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Wang, Moody and UNI1 as applied to claims 1-7, 10, 16 and 27 above, and further in view of Passaris et al. (PLoS One, 2014, 9: e93785; cited on the Form PTO-892 mailed 07/11/2025; herein referred to as Passaris).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 8 is drawn to the composition of claim 2, wherein the amino acid linker comprises SEQ ID NO: 14 as elected.
The teachings of Wang, Moody and UNI1 as applied to claims 1-7, 10, 16 and 27 are discussed above. These references do not teach the sequence limitations of the linker.
Passaris relates to fluorescent reporters [title] comprised of protein fusions [abstract].
Regarding claim 8, Passaris discloses strains comprising fusion peptides of yellow fluorescent protein to the protein translated by the gene iscR [abstract], wherein the fusion comprises a linker with sequence SGGGG [Table 1, ln 9 with Strain name LT2 iscR::yfp], which corresponds to SEQ ID NO: 14.
In view of Passaris, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined fusion of Wang, Moody and UNI1 by replacing the linker of Wang with the linker of Passaris to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the linker of Wang and the linker of Passaris are both peptide linkers used in fusion proteins, and as such both are capable of being incorporated into fusions as described by Wang and Passaris. Thus it would have been obvious to one of ordinary skill in the art to replace the linker of Wang with the linker of Passaris, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both Wang and Passaris disclose fusion proteins comprising linkers.
Therefore, the invention of claim 8 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 12, 14 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, Moody and UNI1 as applied to claims 1-7, 10, 16 and 27 above, and further in view of Vyas et al. (US 2017/0166928; cited on the Form PTO-892 mailed 12/23/2024; herein referred to as Vyas).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 12 is drawn to the composition of claim 1, further comprising a localization domain.
The teachings of Wang, Moody and UNI1 as applied to claims 1-7, 10, 16 and 27 are discussed above. These references do not teach a localization domain.
Vyas discusses compositions and methods for genetically modifying yeast cells using a CRISPR/Cas9 system [abstract], and discloses the system facilitates gene knockouts [para 0004] in an organism traditionally unamenable to genetic manipulation [para 0003], such that the genome is modified to increase or decrease the activity of a gene [para 0010].
Regarding claim 12, Vyas teaches the use of the SV40 nuclear localization signal fused to a Cas9 peptide [para 0111], wherein the nuclear localization signal is understood in the art to be a localization domain.
In view of Vyas, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined invention of Wang, Moody and UNI1 by using the localization domain of Vyas to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined invention of Wang, Moody and UNI1, because Vyas teaches a method of facilitating knockouts in difficult organisms using a Cas9 fused with a nuclear localization signal. One of ordinary skill in the art would have had a reasonable expectation of success because both Wang and Vyas discuss methods of modulating gene activity with Cas9 variants.
Regarding claim 14, Vyas teaches an organism containing a GFP expression construct in [Fig. 11C] and a Cas9 construct in [Fig. 11A] wherein the Cas9 would target the GFP and the loss of detectable GFP signal would indicate successful Cas9 activity [para 0127], wherein GFP is considered to be a detectable domain.
Regarding claim 18, the instant specification does not define a scaffold, but provides examples such as “a nanoparticle, virus-like particle, or other polypeptide scaffold” [p 3]. Therefore the term is being given the plain definition as it is used in the art. In view of this definition, Vyas teaches the fusion of Cas9 to a FLAG-tag [para 0111], which is understood in the art to be a polypeptide used for immobilization, and therefore satisfies the claim limitation of “bound to a scaffold”.
Therefore, the invention of claims 12, 14 and 18 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Wang and Moody and UNI1 as applied to claims 1-7, 10, 16 and 27 above, and further in view of Dahlman et al. (US 2017/0349894; cited on the Form PTO-892 mailed 12/23/2024; herein referred to as Dahlman).
The instant rejection is maintained from a previous Office action and any newly recited portions are necessitated by claim amendment.
Claim 25 is drawn to a pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.
The teachings of Wang, Moody and UNI1 as applied to claims 1-7, 10, 16 and 27 are discussed above. These references do not teach a pharmaceutically acceptable carrier.
Dahlman describes escorted and functionalized CRISPR-Cas systems [title] for the control of gene expression [para 0006], and discloses methods involving the escorted delivery of a CRISPR-Cas system to a selected time or place within a cell so that the activity of the system is spatially or temporally controlled [para 0010].
Regarding claim 25, Dahlman teaches that the system comprising Cas9 can be delivered by delivery systems [para 0194] that contain a pharmaceutically acceptable carrier such as phosphate-buffered saline [para 0196].
In view of Dahlman, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined fusion of Wang, Moody and UNI1 by using the pharmaceutically acceptable carrier of Dahlman, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined fusion of Wang, Moody and UNI1, because Dahlman teaches the use of a pharmaceutically acceptable carrier to deliver Cas9 systems in methods that emphasize spatial and temporal control of Cas9. One of ordinary skill in the art would have had a reasonable expectation of success because both Wang and Dahlman discuss methods of modulating gene activity with Cas9 variants.
Therefore, the invention of claim 25 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on page 7 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends there is no motivation to combine the EB domain and Cas9 because there is no expectation that the fusion has utility within native chromatin structure, and there is no expectation of success that the protein would exhibit the functionality demonstrated by the claimed composition such as fundamentally new mechanistic characteristic properties with locus-specific effects; Applicant further contends there is no teaching or suggestion that the EB domain would retain its structural integrity, folding, binding ability, or functionality when fused to the larger Cas9 protein.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that there is no motivation to combine due to no expectation of utility, Wang specifically teaches Cas9 fusions that are functional to induce site-specific epigenome editing, and Moody teaches EB domains can bind PRC2 to affect histone methyltransferase activity and therefore epigenetic regulation. As the prior art of record teaches the structural components of claimed composition, and provides the motivation from Wang that that sequence-specific DNA-binding proteins such as Cas can recruit epigenetic modifiers to reshape the epigenome at a given locus, and from Moody that the specific EB domain can affect epigenetic regulation by affecting PRC2 histone methyltransferase activity, the claimed composition would have been prima facie obvious as set forth in the rejection above.
Regarding the above assertions regarding unpredictability and a lack of expectation of success, the teachings of the prior art are stated in the rejection above. Briefly, the claims are drawn to a composition comprising an EB domain linked to a Cas9 domain. Wang discusses different Cas9 fusion proteins used for site-specific epigenome editing, specifically a fusion with the activity of localizing to a specific sequence in the genome via Cas9-mediatd sequence recognition, which facilitates the fusion partner (KRAB) to induce methylation of the local histone for the suppression of globin genes. Therefore the fusion of Wang is understood to have an activity affecting epigenetic regulation of target genes. While Wang doesn’t teach or suggest a Cas9 fusion with an EB domain, Moody describes EB domains and their activity against PRC2, a histone methyltransferase, which has an activity similar to KRAB in affecting histone methylation. One of skill in the art would have recognized that both KRAB and EB have similar activities to affect epigenetic regulation, and would have been motivated to modify the fusion of Wang to include the EB domain of Moody since Wang teaches a Cas9-directed fusion capable of site-directed epigenetic regulation, and Moody teaches the EB domain can affect epigenetic regulation. One of ordinary skill in the art would have had a reasonable expectation of success in modifying the fusion of Wang by using the EB domain of Moody because both Wang and Moody discuss methods of epigenetic regulation involving peptides that affect histone methylation.
Regarding the assertions against the expectation of utility of the prior art combination, of the functionality demonstrated of the claimed composition, and of the folding of the EB domain, each of these elements are functional characteristics of the claimed composition that are not recited in the claims. Additionally, each of these functional elements is considered to be connected to the structure of the claimed invention, as the claims only recite a fusion protein with specific structural limitations. Therefore, the utility, the functionality, and the folding of the claimed fusion are considered to be inherent to the structure of the claimed fusion. As the combination of prior art teaches and/or suggests a fusion that satisfies the structural limitations of the claims, the fusion of the prior art is therefore considered to have the utility, functionality and folding of the claimed fusion (see MPEP 2112.01.I).
Conclusion
Status of the Application:
Claims 1-8, 10, 12, 14, 16, 18-21, 25, 27 and 30 are pending.
Claims 19-21 and 30 are withdrawn.
Claims 1-8, 10, 12, 14, 16, 18, 25 and 27 are rejected.
No claim is in condition for allowance.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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, Manjunath Rao can be reached at (571) 272-0939. 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.
/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
PNG
media_image1.png
210
648
media_image1.png
Greyscale
Sequence alignment of SEQ ID NO: 13 with GenPept Accession No. 5WP3_B (reference MOODY2), wherein the line denotes the motif recited in claims 3-5.
APPENDIX B
PNG
media_image2.png
398
648
media_image2.png
Greyscale
Sequence alignment of SEQ ID NO: 34 with UniProt Accession No. A0A386IRG9_STAAU (reference UNI1)
APPENDIX C
PNG
media_image3.png
395
650
media_image3.png
Greyscale
Sequence alignment of SEQ ID NO: 37 with the combined fusion comprising the EB domain of Moody and the Cas9 of UNI1, wherein the EB domain is at the N-terminus.