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. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/20/2026 has been entered.
3. Applicant’s amendment to the claims filed on 03/20/2026 in response to the Final Rejection mailed on 02/25/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
4. Claims 25-45 are pending.
5. Claims 42-45 stand withdrawn pursuant to 37 CFR 1.142(b).
6. Applicant’s remarks filed on 03/20/2026 in response to the Final Rejection mailed on 02/25/2025 have been fully considered and are deemed not persuasive to overcome 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.
Claim Rejections - 35 USC § 103
7. The rejection of claims 25-29 and 31-41 under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2014/204729 A1; cited on IDS filed on 05/09/2024) in view of Prakash et al. (US Patent Application Publication 2015/0315594 A1; cited on IDS filed on 05/09/2024) as evidenced by GenBank Q99ZW2.1 (GenBank, 2014; cited on IDS filed on 05/09/2024) is maintained for the reasons of record and the reasons set forth below.
8. Claims 25-29 and 31-41 are drawn to a composition for producing a population of cells comprising a modification in the Angiopoeitin-like 3 (ANGPTL3) gene, comprising: (a) a guide RNA (gRNA) that targets an ANGPTL3 genomic locus (ANGPTL3 gRNA), or a nucleic acid encoding an ANGPTL3 gRNA; and (b) a Cas9 endonuclease or a nucleic acid encoding a Cas9 endonuclase; wherein the ANGPTL3 gRNA comprises a spacer sequence that is a RNA sequence having the nucleic acid sequence of SEQ ID NO: 9199, 9109, 7094, 7168, 7061, 7165, or 9110 in which T is substituted for U.
9. With respect to claim 25, Zhang et al. teach engineering and optimization systems for manipulation of sequences and/or activities of target sequences comprising single gRNA sequence and an RNA-guided endonuclease such as Cas9 for introduction into a cell for modification of the ANGPTL3 genomic locus [see Abstract; paragraphs 0006-0012; 0086; 00212; 00257].
With respect to claim 26, Zhang et al. teach wherein the Cas9 is a S. pyogenes Cas9, S. aureus Cas9, and S. thermophilus Cas9 [see paragraph 0021].
With respect to claim 27, Zhang et al. teach wherein the Cas9 is a S. pyogenes Cas9 [see paragraph 0021]. Although Zhang et al. does not explicitly teach wherein the endonuclease comprises the sequence of SEQ ID NO: 1, evidentiary reference of Genbank Q99ZW2 is cited to demonstrate that the S. pyogenes Cas9 shares an amino acid sequence that is 100% identical to SEQ ID NO: 1 [see alignment attached as APPENDIX B].
With respect to claim 28, Zhang et al. teach wherein the gRNA is a single guide RNA [see Abstract; paragraphs 0006-0012; 0086; 00212; 00257].
With respect to claim 31, Zhang et al. teach wherein the gRNA and RNA guided nuclease are formulated as a ribonucleoprotein particle [see Abstract; paragraphs 0006-0012; 0086; 00212; 00257].
With respect to claims 32-33, Zhang et al. teach wherein the nucleic acid is present in a viral vector such as an adeno-associated viral vector [see paragraph 0104].
With respect to claims 34-39, it is noted that the limitations regarding a population of cells do not further limit the structure of the claims because the claims are drawn to a composition and not a method; nevertheless, Zhang et al. teach wherein the gRNA and the RNA guided endonuclease are formulated into a liposome or lipid nanoparticle [see paragraph 00112], the cells comprise hepatocytes [see paragraph 0027], wherein the subject has an ANGPTL3-related condition [see paragraph 0086]; and wherein the subject is human [see paragraph 0097].
With respect to claim 41, Zhang et al. teach the composition comprising an mRNA encoding a Cas9 endonuclease [see paragraph 0423].
However, Zhang et al. does not teach the composition wherein the ANGPTL3 gRNA comprises a spacer sequence that is a RNA sequence having the nucleic acid sequence of SEQ ID NO: 9199, 9109, 7094, 7168, 7061, 7165, or 9110 in which T is substituted for U; the composition of claim 29, wherein the gRNA is a chemically modified gRNA; and the composition of claim 40, wherein the ANGPTL3 gRNA comprises a spacer sequence that is a RNA sequence and comprises the sequence of SEQ ID NO: 7094 in which T is substituted for U.
Prakash et al. teach systems for producing a population of ANGPTL3 modified cells comprising an antisense RNA targeted the ANGPTL3 gene and producing a population of cells comprising a modification in the ANGPTL3 gene wherein the antisense RNA targets a nucleotide sequence in order to treat, prevent, delay or ameliorate any one or more of cardiovascular disease and/or metabolic disease and/or symptom thereof [see Abstract; paragraphs 0009-0017; 0023]. Although the breadth of the claims is sufficiently broad to encompass fragments of the claimed sequences [see 112(b) rejection above], Prakash et al. teach an antisense RNA targeted the ANGPTL3 gene that is 100% identical to SEQ ID NO: 7094 and 9199 [see alignment attached as APPENDIX A]. Prakash et al. teach wherein the RNA is chemically modified [see paragraph 0014], and wherein at least 50% of the cells of the population comprise a modification in the ANGPTL3 gene [see paragraphs 0579 and 1028].
Given that it is known that uracil is present in RNA and thymine is present in DNA, it would be obvious for one of ordinary skill in the art when targeting a DNA strand for hybridization to substitute a thymine in place of the uracil.
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 Prakash et al. to develop compositions for targeting a specific region in the ANGPTL3 genome locus to reduce expression of the ANGPTL3 protein to treat cardiovascular and metabolic disease because Zhang et al. teach gRNA/Cas9 endonuclease targeting of genomic coding regions such as the ANGPTL3 locus that provides an affordable, easy to set up, scalable, and amenable to targeting multiple positions within the eukaryotic genome. Prakash et al. teach systems for antisense RNA targeting of the ANGPTL3 locus. 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 Prakash et al. to use the target sequences of Prakash et al. to design gRNA/Cas9 proteins in Zhang et al. because Prakash et al. acknowledges antisense RNA for targeting ANGPTL3 for treating cardiovascular and metabolic disease and Zhang et al. acknowledges that these compositions provide an affordable, easy to set up, scalable, and amenable to targeting multiple positions within the eukaryotic genome. It would require simple substitution to develop gRNA targeting identical sequences using the Cas9 technology as taught by Zhang et al. 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.
10. The rejection of claim 30 under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2014/204729 A1; cited on IDS filed on 05/09/2024) in view of Prakash et al. (US Patent Application Publication 2015/0315594 A1; cited on IDS filed on 05/09/2024) as evidenced by GenBank Q99ZW2.1 (GenBank, 2014; cited on IDS filed on 05/09/2024) as applied to claims 25-29 and 31-41, and further in view of Renaud et al. (Cell Reports, March 2016; cited on IDS filed on 05/09/2024) is maintained for the reasons of record and the reasons set forth below.
11. The relevant teachings of Zhang et al. and Prakash et al. as applied to claims 25-29 and 31-41 are set forth above.
With respect to claim 30, Prakash et al. teach the method wherein the chemically modified gRNA comprises a phosphorothioated 2’-O-methyl nucleotides at the 3’end and the 5’end of the gRNA [see paragraphs 0014-0016 and 0805].
However, the combination of Zhang et al. and Prakash et al. do not teach the method of using phosphorothioated 2’-O-methyl nucleotides in the context of a gRNA Cas9 system.
Renaud et al. teach that phosphorothioated-modified oligonucleotides strongly enhance genomic editing efficiency of single-stranded oligonucleotides donors in cultured cells using CRISPR-Cas9 nucleases [see Abstract].
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., Prakash et al., and Renaud et al. to using phosphorothioated sgRNA in the compositions of Zhang et al. and Prakash et al. because Zhang et al. and Prakash et al. teach compositions for Cas9 modification of the ANGPTL3 genomic locus. Renaud et al. teach that phosphorothioated-modified oligonucleotides strongly enhance genomic editing efficiency of single-stranded oligonucleotides donors in cultured cells using CRISPR-Cas9 nucleases. 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., Prakash et al., and Renaud et al. because Renaud et al. acknowledges that phosphorothioated-modified oligonucleotides strongly enhance genomic editing efficiency of single-stranded oligonucleotides donors in cultured 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
12. Beginning on p. 5 of applicants’ remarks, applicants in summary contend that the art is unpredictable and allege that Prakash’s SEQ ID NO: 2192 which is alleged to be identical to SEQ ID NO: 9199 demonstrates a 20% in vitro inhibition in Prakash whereas in the claimed platform shows 97.6% cutting efficiency. Applicants further contend that Zhang merely teaches general methods for delivery, engineering, and optimization of systems, methods and compositions for manipulation of sequences and/or activities of target sequences and only mentions ANGPTL3 in a laundry list of target genes. Applicants contend that stating it would require simple substitution to develop gRNA targeting identical sequences using Cas9 technology as taught by Zhang is predictable based on the art. Applicants contend that there is nothing in Prakash that would provide any teaching, suggestion, or motivation to guide a skilled person to select Prakash’s SEQ ID NO: 2192, which is identical to the claimed SEQ ID NO: 9199 because this sequence in Prakash only shows 20% inhibition of ANGPTL3 mRNA, and therefore, would lead one of ordinary skill in the art away from claimed invention. Applicants contend that the obviousness analysis used by the examiner appears to have no other basis than Applicants’ disclosure using impermissible hindsight.
These argument is found to be not persuasive because the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, and as stated in the rejection above, Zhang et al. acknowledges that these compositions provide an affordable, easy to set up, scalable, and amenable to targeting multiple positions within the eukaryotic genome.
Furthermore, the Federal Circuit in Meiresonne v. Google, Inc. (Fed. Cir. March 7, 2017) found that “[o]bviousness may be defeated if the prior art indicates that the invention would not have worked for its intended purpose or other-wise teaches away from the invention. DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1326 (Fed. Cir. 2009). A reference teaches away ‘when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken’ in the claim. Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731, 738 (Fed. Cir. 2013). A reference that ‘merely expresses a general preference for an alternative invention but does not criticize, discredit, or otherwise discourage investigation into’ the claimed invention does not teach away. Id. To reverse a finding of obviousness based on overlooking a ‘teach away’, the evidence must show that the references discouraged the combination or implied that the resulting combination would not work as described in the patent”. In the instant case, while the sequence of Prakash et al. may have shown 20% inhibition of ANGPTL3 mRNA, there is no indication in Prakash et al. that would discourage of imply that the sequence would not work as described.
It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Given the teachings of Zhang et al., one of ordinary skill in the art would expect a system for targeting ANGPTL3 genomic locus using a CRISPR/Cas platform to have higher cutting efficiencies. As stated in the rejection above, Zhang et al. teach methods for delivery, engineering and optimization of systems for manipulation of sequences and/or activities of target sequences comprising single gRNA sequence and an RNA-guided endonuclease such as Cas9 for introduction into a cell for modification of the ANGPTL3 genomic locus [see Abstract; paragraphs 0006-0012; 0086; 00212; 00257]. Zhang et al. teach that these techniques are affordable, easy to set up, scalable, and amenable to targeting multiple positions within the eukaryotic genome. Furthermore, Zhang et al. demonstrates efficient DNA cleavage using SpCas9 systems with multiple different gRNAs [see paragraphs 00186, 00193, 00210, 00216, 00226]. Additionally, Zhang et al. teach that the CRISPR-Cas system offers the ability to reduce the off-targeting potential of antisense sequences (resulting in lower efficiency) [see paragraph 00695]. As such, one of ordinary skill in the art would have a reasonable expectation that a substitution of the antisense technology of Prakash et al. with the CRISPR-Cas system Zhang et al. would increase the overall targeting and cutting efficiency of the system.
Conclusion
13. Status of the claims:
Claims 25-45 are pending.
Claims 42-45 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 25-41 are rejected.
No claims are in condition for an 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 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
Prakash et al. with SEQ ID NO: 7094
Query Match 100.0%; Score 20; DB 33; Length 20;
Best Local Similarity 100.0%;
Matches 20; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TAAGACCATGTCCCAACTGA 20
||||||||||||||||||||
Db 1 TAAGACCATGTCCCAACTGA 20
Prakash et al. with SEQ ID NO: 9199
Query Match 100.0%; Score 20; DB 52; Length 20;
Best Local Similarity 100.0%;
Matches 20; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CAAAGACCTTCTCCAGACCG 20
||||||||||||||||||||
Db 20 CAAAGACCTTCTCCAGACCG 1
APPENDIX B
GenBank Q99ZW2.1
Query Match 100.0%; Score 7005; DB 1; Length 1368;
Best Local Similarity 100.0%;
Matches 1368; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE 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 LLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA 360
Qy 361 GYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELH 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELH 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 IVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL 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 YSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPK 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 YSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPK 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