DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicants’ amendment to the claims filed on 12/26/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-7, 9-10, 12, 25, 27-30, and 37-41 are pending.
Election/Restrictions
4. Applicant’s election of Group I, claims 1-7, 9-10, 12, and 37-39 in the reply filed on 12/26/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
5. Claims 25, 27-30, and 40-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/26/2025.
Claims 1-7, 9-10, 12, and 37-39 are pending and examined on the merits.
Priority
6. Acknowledgement is made of applicants’ claimed domestic priority to U.S. Provisional Application No. 63/132,286 and 63/104,343, filing date 12/30/2020 and 10/22/2020, respectively.
Information Disclosure Statement
7. The IDSs filed on 04/21/2023, 09/22/2023, 05/17/2024, and 09/27/2024 have been considered by the examiner and a copies of the Form PTO/SB/08 are attached to the office action.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figures 4 and 8.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(b)
8. 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.
9. Claims 37 and 39 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.
Regarding claim 37, the recitation of “wherein the at least one encoded polypeptide comprises the sequence set forth…” is indefinite because SEQ ID NO: 58 is the only sequence listed in the claims that is represented by an amino acid sequence (polypeptide) whereas SEQ ID NOs: 57, 62 and 63 are nucleic acid sequences. It is therefore unclear how SEQ ID NOs: 57, 62, and 63 can represent a polypeptide when they represent nucleic acids. It is suggested that applicants clarify the meaning of the claims.
Regarding claim 39, the recitation of “The isolated nucleic acid molecule of claim 2, wherein the Cas9 comprises a sequence having at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identity to the sequence set forth in SEQ ID NO: 64 or SEQ ID NO: 65…” is indefinite because SEQ ID NO: 64 and 65 are amino acid sequences; however, the claims are drawn to a nucleic acid. It is unclear how an amino acid sequence is representative of a nucleic acid. It is suggested that applicants clarify the meaning of the claims.
Claim Rejections - 35 USC § 103
10. 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.
11. Claim(s) 1-7, 9, 12 and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0283743 A1; cited on IDS filed 04/21/2023) in view of Offen et al. (WO 2018/178994 A1; examiner cited) as evidenced by Charpentier et al. (WO 2013/176772 A1; examiner cited).
12. Claims 1-5 and 39 are drawn to an isolated nucleic acid molecule, comprising: a nucleic acid sequence encoding (i) a Cas endonuclease, (ii) at least one polypeptide having repressor activity, and (iii) at least one guide RNA designed to target (i) exon 4 of the APOE gene, (ii) the promoter region of the APOE gene, or (iii) a regulatory element within the APOE gene.
Claims 6-7 and 9 are drawn to a viral vector comprising the isolated nucleic acid molecule of claim 1.
13. With respect to claim 1, Zhang et al. teach an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a Cas endonuclease, at least one polypeptide having repressor activity and at least one gRNA designed to target the APOE gene [see paragraphs 0011-0012, 0055, 0718, 0739, and 1248-1250].
With respect to claim 2, Zhang et al. teach the isolated nucleic acid molecule wherein the Cas endonuclease comprises Cas9 or VRER Cas9 [see Abstract; paragraph 0021].
With respect to claim 3, Zhang et al. teach the isolated nucleic acid molecule wherein the at least one encoded polypeptide having repressor activity comprises Kruppel associated box domain [see paragraph 0717].
With respect to claim 5, Zhang et al. teach the isolated nucleic acid molecule wherein the Cas endonuclease comprises Cas9 VRER and the polypeptide having repressor activity comprises Kruppel-associated box [see paragraphs 0021 and 0717].
With respect to claim 6, Zhang et al. teach a viral vector comprising the isolated nucleic acid molecule comprising a nucleic acid sequence encoding a Cas endonuclease, at least one polypeptide having repressor activity and at least one gRNA designed to target the APOE gene [see paragraphs 0011-0012, 0055, 0718, 0739, 0744, and 1248-1250].
With respect to claim 7, Zhang et al. teach the viral vector wherein the viral vector comprises one or more promoters operably linked to the isolated nucleic acid molecule and wherein the one or more promoters drive the expression of the at least one gRNA and the Cas9 endonuclease [see paragraphs 0762-0764].
With respect to claim 9, Zhang et al. teach the viral vector wherein the viral vector comprises one or more regulatory elements [see paragraph 0764].
With respect to claim 12, Zhang et al. teach the viral vector wherein the viral vector is a lentiviral vector [see paragraph 0147].
With respect to claim 39, Zhang et al. teach the isolated nucleic acid molecule wherein the Cas9 is a S. aureus and/or a S. pyogenes Cas9 [see paragraph 0724]. Although Zhang et al. does not explicitly teach that the sequence comprises at least 75%, at least 80%, at least 85%, at least 90% or at least 95% identity to the sequence set forth in SEQ ID NO: 64 or SEQ ID NO: 65, evidentiary reference of Charpentier et al. (WO 2013/176772 A1; examiner cited) is cited to demonstrate that S. aureus and/or a S. pyogenes Cas9 share 100% sequence identity to SEQ ID NO: 64 and 65, respectively [see alignments attached as APPENDIX A].
However, Zhang et al. does not explicitly teach wherein the one guide RNA is designed to target exon 4 of the APOE gene, the promoter region of the APOE gene, or a regulatory element within the APOE gene of claim 1 and wherein the at least one gRNA is designed to target a protospacer-adjacent motif (PAM) created by a SNP rs429358 in exon 4 of the APOE gene.
Offen et al. teach targeted elimination of APOE gene using CRISPR technology wherein the gRNA targets exon 4 and a PAM sequence created by SNP rs429358 in exon 4 of the APOE gene for the treatment of Alzheimers’ [see Abstract; p. 3-4, 10].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Zhang et al. and Offen et al. according to the teachings of Offen et al. to target APOE gene because Zhang et al. teach Cas/repressor effectors for targeting the APOE gene. Offen et al. teach similar compositions designed to target exon 4 of the APOE gene for the treatment of Alzheimer’s. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would have been motivated to combine the teachings of Zhang et al. and Offen et al. because Offen et al. acknowledges that targeted elimination of the APOE gene is useful in the treatment of Alzheimer’s. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
14. Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0283743 A1; cited on IDS filed 04/21/2023) in view of Offen et al. (WO 2018/178994 A1; examiner cited) as applied to claims 1-7, 9, 12 and 39 above, and further in view of Ortinski et al. (Molecular Therapy, 2017; cited on IDS filed on 04/21/2023).
15. The relevant teachings of Zhang et al. and Offen et al. as applied to claims 1-7, 9, 12 and 39 are set forth above.
With respect to claim 10, Zhang et al. teach the viral vector wherein the viral vector comprises one or more regulatory elements [see paragraph 0764], and wherein the viral vector is a lentiviral vector [see paragraph 0147]. Zhang et al. further teach that regulatory elements include LTR promoters, CMV enhancers, WPRE and SV40 [see paragraph 0764].
However, Zhang et al. and Offen et al. do not explicitly teach wherein the one or more regulatory elements comprise a Sp1 responsive element, a p2A signal, a woodchuck hepatitis virus post-transcriptional regulatory element, a Phi signal-packaging signal, a rev responsive element, a 5’-LTR, and a 3’-LTR.
Ortinski et al. teach lentiviral based delivery platforms for CRISPR/Cas9 systems comprising Sp1, P2A, WPRE, RRE and 3’ and 5’ LTR regulatory elements that demonstrate increased production efficacy that can mediate rapid and robust gene editing in eukaryotic cells [see Abstract; Figure 1].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Zhang et al., Offen et al. and Ortinski et al. to include Sp1, P2A, WPRE, RRE and 3’ and 5’ LTR regulatory elements in the viral vector systems of Zhang et al. and Offen et al. because Zhang et al. and Offen et al. teach CRISPR/Cas9 viral vector systems for targeted modification of the APOE gene in cells. Ortinski et al. teach similar vectors comprising Sp1, P2A, WPRE, RRE and 3’ and 5’ LTR regulatory elements that demonstrate increased production efficacy that can mediate rapid and robust gene editing in eukaryotic cells. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would have been motivated to combine the teachings of Zhang et al., Offen et al. and Ortinski et al. because Ortinski et al. acknowledges that these regulatory elements demonstrate increased production efficacy that can mediate rapid and robust gene editing in eukaryotic cells. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
16. Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US Patent Application Publication 2020/0283743 A1; cited on IDS filed 04/21/2023) in view of Offen et al. (WO 2018/178994 A1; examiner cited) as applied to claims 1-7, 9, 12 and 39 above, and further in view of Cole et al. (WO 2022/066956 A1, priority to 09/24/2020; examiner cited).
17. The relevant teachings of Zhang et al. and Offen et al. as applied to claims 1-7, 9, 12 and 39 are set forth above.
However, the combination of Zhang et al. and Offen et al. do not teach the isolated nucleic acid molecule of claim 38 wherein the at least one gRNA designed to target exon 4 of the APOE gene comprises the sequence set forth in any one of SEQ ID NO: 5-SEQ ID NO: 14.
Cole et al. teach compositions designed to reduce the amount of APOE expression in a cell for the treatment of dementia comprising inhibitory RNA compounds that share 100% sequence identity to the nucleic acid sequences of SEQ ID NO: 10 and 12 [see alignments attached as APPENDIX B; Abstract; p. 2, p. 10].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Zhang et al., Offen et al. and Cole et al. to modify the siRNA of Cole et al. into gRNA targeting the same region of the APOE gene because Zhang et al. and Offen et al. teach CRISPR/Cas9 viral vector systems for targeted modification of the APOE gene in cells for the treatment of Alzheimer’s. Cole et al. teach inhibitory RNA oligonucleotides that target APOE for the treatment of Alzheimer’s. It would require only routine skill for one of ordinary skill in the art to convert the inhibitory RNA oligonucleotides of Cole et al. into gRNA in the compositions of Zhang et al. and Offen et al. in order to target the same site in the APOE gene for the treatment of Alzheimer’s. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
18. Status of the claims:
Claims 1-7, 9-10, 12, 25, 27-30, and 37-41 are pending.
Claims 25, 27-30, and 40-41 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-7, 9-10, 12, and 37-39 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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.
/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
APPENDIX A
Charpentier et al. with SEQ ID NO: 64
Query Match 100.0%; Score 5433; Length 1053;
Best Local Similarity 100.0%;
Matches 1053; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRR 60
Qy 61 RHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHN 120
Qy 121 VNEVEEDTGNELSTKEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VNEVEEDTGNELSTKEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEA 180
Qy 181 KQLLKVQKAYHQLDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KQLLKVQKAYHQLDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYF 240
Qy 241 PEELRSVKYAYNADLYNALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PEELRSVKYAYNADLYNALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIA 300
Qy 301 KEILVNEEDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 KEILVNEEDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQS 360
Qy 361 SEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 SEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNR 420
Qy 421 LKLVPKKVDLSQQKEIPTTLVDDFILSPVVKRSFIQSIKVINAIIKKYGLPNDIIIELAR 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LKLVPKKVDLSQQKEIPTTLVDDFILSPVVKRSFIQSIKVINAIIKKYGLPNDIIIELAR 480
Qy 481 EKNSKDAQKMINEMQKRNRQTNERIEEIIRTTGKENAKYLIEKIKLHDMQEGKCLYSLEA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 EKNSKDAQKMINEMQKRNRQTNERIEEIIRTTGKENAKYLIEKIKLHDMQEGKCLYSLEA 540
Qy 541 IPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVKQEENSKKGNRTPFQYLSSSDSKIS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 IPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVKQEENSKKGNRTPFQYLSSSDSKIS 600
Qy 601 YETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKDFINRNLVDTRYATRGLMNLL 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 YETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKDFINRNLVDTRYATRGLMNLL 660
Qy 661 RSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAEDALIIANADFIFKEWKK 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAEDALIIANADFIFKEWKK 720
Qy 721 LDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKDYKYSHRVDKKPN 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 LDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKDYKYSHRVDKKPN 780
Qy 781 RELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHHDPQTYQKL 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 RELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHHDPQTYQKL 840
Qy 841 KLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDDYPNS 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 KLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDDYPNS 900
Qy 901 RNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQA 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 RNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQA 960
Qy 961 EFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTI 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 EFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTI 1020
Qy 1021 ASKTQSIKKYSTDILGNLYEVKSKKHPQIIKKG 1053
|||||||||||||||||||||||||||||||||
Db 1021 ASKTQSIKKYSTDILGNLYEVKSKKHPQIIKKG 1053
Charpentier et al. with SEQ ID NO: 65
Query Match 100.0%; Score 7005; Length 1368;
Best Local Similarity 100.0%;
Matches 1368; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDKKYSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDKKYSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE 60
Qy 61 ATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFG 120
Qy 121 NIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSD 180
Qy 181 VDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGN 240
Qy 241 LIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAI 300
Qy 301 LLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA 360
Qy 361 GYIDGGASQEEFYKFIKPILEKMDGTEELLAKLNREDLLRKQRTFDNGSIPHQIHLGELH 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GYIDGGASQEEFYKFIKPILEKMDGTEELLAKLNREDLLRKQRTFDNGSIPHQIHLGELH 420
Qy 421 AILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEE 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 AILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEE 480
Qy 481 VVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 VVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFL 540
Qy 541 SGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKI 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKI 600
Qy 601 IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWG 660
Qy 661 RLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSL 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSL 720
Qy 721 HEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRER 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 HEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRER 780
Qy 781 MKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDH 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 MKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDH 840
Qy 841 IVPQSFIKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IVPQSFIKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL 900
Qy 901 TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS 960
Qy 961 KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK 1020
Qy 1021 MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDF 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDF 1080
Qy 1081 ATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVA 1140
Qy 1141 YSVLVVAKVEKGKSKKLKSVKELLGLTIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPK 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 YSVLVVAKVEKGKSKKLKSVKELLGLTIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPK 1200
Qy 1201 YSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVE 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 YSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVE 1260
Qy 1261 QHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 QHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGA 1320
Qy 1321 PAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD 1368
||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 PAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD 1368
APPENDIX B
Cole et al. with SEQ ID NO: 10
Query Match 100.0%; Score 20; Length 20;
Best Local Similarity 100.0%;
Matches 20; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TCGGGCTTGGGGAGAGGAGG 20
||||||||||||||||||||
Db 20 TCGGGCTTGGGGAGAGGAGG 1
Cole et al. with SEQ ID NO: 12
Query Match 100.0%; Score 20; Length 20;
Best Local Similarity 100.0%;
Matches 20; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TGTGAAGGGAGAATGAGGAA 20
||||||||||||||||||||
Db 20 TGTGAAGGGAGAATGAGGAA 1