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 04/29/2026 in response to the Non-Final Rejection mailed on 02/03/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claim 38 is cancelled.
4. Claims 1-7, 9-10, 12, 25, 27-30, 37, and 39-41 are pending.
5. Claims 25, 27-30 and 40-41 stand withdrawn pursuant to 37 CFR 1.142(b).
6. Applicant’s remarks filed on 04/29/2026 in response to the Final Rejection mailed on 02/03/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Nucleotide and/or Amino Acid Sequence Disclosures
7. The objection to the specification and drawings under 37 CFR 1.821 is withdrawn in view of applicants’ amendment to the specification and drawings to include appropriate sequence identifiers.
Claim Rejections - 35 USC § 112(b)
8. The rejection of claims 37 and 39 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for indefiniteness is withdrawn in view of applicants’ amendment to the claims.
Claim Rejections - 35 USC § 103
9. The rejection of claims 1-7, 9, 12, and 39 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; cited on PTO-892 mailed on 02/03/2026) as evidenced by Charpentier et al. (WO 2013/176772 A1; cited on PTO-892 mailed on 02/03/2026) is withdrawn in view of applicants’ amendment to the claims to recite “wherein the at least one gRNA comprises the sequence set forth in any one of SEQ ID NO: 5 – SEQ ID NO: 12”.
10. The rejection of claim 10 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; cited on PTO-892 mailed on 02/03/2026) 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 (Molecular Therapy, 2017; cited on IDS filed on 04/21/2023) is withdrawn in view of applicants’ amendment to the claims to recite “wherein the at least one gRNA comprises the sequence set forth in any one of SEQ ID NO: 5 – SEQ ID NO: 12”.
11. The rejection of claim 38 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; cited on PTO-892 mailed on 02/03/2026) 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; cited on PTO-892 mailed on 02/03/2026) is withdrawn in view of applicants’ amendment to the claims to cancel claim 38.
12. Claims 1-7, 9, 12, and 39 are newly 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; cited on PTO-892 mailed on 02/03/2026) and Cole et al. (WO 2022/066956 A1, priority to 09/24/2020; cited on PTO-892 mailed on 02/03/2026), as evidenced by Charpentier et al. (WO 2013/176772 A1; cited on PTO-892 mailed on 02/03/2026). This new grounds of rejection is necessitated by applicants’ amendment to claim 1 to recite “wherein the at least one gRNA comprises the sequence set forth in any one of SEQ ID NO: 5 – SEQ ID NO: 12”.
13. As amended, claims 1-5 and 39 are drawn to a 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, wherein the at least one gRNA comprises the sequence set forth in any one of SEQ ID NO: 5 – SEQ ID NO: 12.
Claims 6-7 and 9 are drawn to a viral vector comprising the nucleic acid molecule of claim 1.
14. 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; cited on PTO-892 mailed on 02/03/2026) 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, wherein the at least one gRNA comprises the sequence set forth in any one of SEQ ID NO: 5 – SEQ ID NO: 12 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].
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 for one of ordinary skill in the art to combine the teachings of Zhang et al., Offen et al., and Cole 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. Cole et al. teach inhibitory RNA oligonucleotides that target APOE 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., Offen et al., and Cole et al. because Offen et al. acknowledges that targeted elimination of the APOE gene is useful in 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.
15. Claim 10 is newly 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; cited on PTO-892 mailed 02/03/2026) and Cole et al. (WO 2022/066956 A1, priority to 09/24/2020; cited on PTO-892 mailed on 02/03/2026) 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). This new grounds of rejection is necessitated by applicants’ amendment to claim 1 to recite “wherein the at least one gRNA comprises the sequence set forth in any one of SEQ ID NO: 5 – SEQ ID NO: 12”.
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.
Response to Remarks Regarding Prior Art Rejections
16. Beginning on p. 10 of applicants’ remarks, applicants in summary contend that Cole’s disclosure of 9000 nucleotides from the APOE sequence is not a teaching or a suggestion of gRNAs that target the claimed regions of the APOE genes, and Cole fails to motivate the skilled person to combine its RNAi with the methods of Zhang and Offen because Cole is not a disclosure of gene editing via CRISPR and one would not consider abandoning the thousands of inhibitory RNA oligonucleotides in favor of a CRISPR approach given their differences.
These arguments are found to be not persuasive for the reasons set forth above and below. Regarding the sequences, the alignments of SEQ ID NOs 10 and 12 represent oligomer nucleotides in Cole et al. that are designed for targeting the APOE reduce the amount of APOE expression in a cell for the treatment of dementia. These sequences respectively are SEQ ID NO: 1861 and 2525 set forth in Tables 30 and 56 of Cole et al. To this end, one of ordinary skill in the art would expect that these oligomers would be obvious variants of each other based on the teachings of Cole et al. and their ability to reduce the expression of APOE.
Regarding applicants’ arguments that inhibitory RNA and CRISPR technology are not applicable to each other and one of ordinary skill would not go from an inhibitory RNA to CRISPR gene editing, this argument is found to be not persuasive because evidentiary evidence of Unniyampurath (Internation Journal of Molecular Sciences, 2016; examiner cited) discloses that over the past decade, RNAi based technologies widely dominated various research applications involving experimental modulation of gene expression at the post-transcriptional level; however, CRISPR gene editing technology has quickly received unprecedented acceptance in the science community dues to its ability to introduce heritable precision insertions and deletions in eukaryotic genome and may occupy the roles currently served by RNAi and may make RNAi obsolete [see Abstract]. As such, it is the examiner’s position that it is within the level of one of ordinary skill in the art to navigate to a gene editing platform to target the APOE gene for introducing heritable genetic traits, and one of ordinary skill in the art would look to regions of the APOE gene as taught by Cole et al. for targeting editing to produce the same outcome of reduced APOE expression.
Conclusion
17. Status of the claims:
Claims 1-7, 9-10, 12, 25, 27-30, 37, and 39-41 are pending.
Claims 25, 27-30 and 40-41 stand withdrawn pursuant to 37 CFR 1.142(b).
Claim 37 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1-7, 9-10, 12, and 39 are rejected.
No claims are in condition for an allowance.
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.
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.
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/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
Prosecution Insights