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. Applicant’s amendment to the claims filed on 07/17/2026 in response to the Non-Final Rejection mailed on 04/24/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claim 2 is cancelled.
4. Claims 1, 3-9, and 11-12 are pending.
5. Applicant’s remarks filed on 07/17/2026 in response to the Non-Final Rejection mailed on 04/24/2026 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.
Claim Rejections - 35 USC § 112(b)
6. The rejection of claim 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for lack of antecedent basis is withdrawn in view of applicants’ amendment to the claims to recite “a nucleic acid encoding…”.
Claim Rejections - 35 USC § 102
7. The rejection of claims 1, 5, 7-9, and 11-12 under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (WO 2020/124481, 06/25/2020; cited on PTO-892 mailed on 04/24/2026) is withdrawn in view of applicants’ amendment to claim 1 to require all three mutations K56Q, A61T and E507K.
8. The rejection of claims 1, 3, 5, 7-9, and 11-12 under 35 U.S.C. 102(a)(1) as being anticipated by Schafer et al. (US 2014/0030765 A1; cited on IDS filed on 06/20/2024) is withdrawn in view of applicants’ amendment to claim 1 to require all three mutations K56Q, A61T, and E507K.
Claim Rejections - 35 USC § 103
9. The rejection of claims 2 and 6 under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2020/124481, 06/25/2020; cited on PTO-892 mailed on 04/24/2026 with machine translation attached) in view of Schafer et al. (US 2014/0030765 A1; cited on IDS filed on 06/20/2024) is withdrawn in view of the cancellation of claim 2, and in favor of the new rejection set forth below, which is necessitated by applicants’ amendment to claim 1 to require all three mutations K56Q, A61T, and E507K.
10. The rejection of claim 4 under 35 U.S.C. 103 as being unpatentable over Schafer et al. (US 2014/0030765 A1; cited on IDS filed on 06/20/2024) in view of Louwrier et al. (Enzyme and Microbial Technology, 2005; cited on PTO 892 mailed on 04/24/2026) is withdrawn for the reasons set forth above regarding Schafer et al.
11. Claims 1, 3, 5-9 and 11-12 are newly rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2020/124481, 06/25/2020; cited on PTO-892 mailed on 04/24/2026 with machine translation attached) in view of Schafer et al. (US 2014/0030765 A1; cited on IDS filed on 06/20/2024). This new grounds of rejection is necessitated by applicants’ amendment to claim 1 to require all three mutations K56Q, A61T, and E507K.
12. With respect to claim 1, Zhang et al. teach a DNA polymerase mutant with enhanced enzyme activities comprising a K56Q and E507K mutation in relation to the wild type DNA polymerase set forth in SEQ ID NO: 1 [see Abstract; paragraphs 0013-0015; alignment attached as APPENDIX A].
With respect to claim 5, Zhang et al. teach a nucleic acid encoding the DNA polymerase [see paragraph 0018].
With respect to claim 6, Zhang et al. teach a DNA polymerase mutant with enhanced enzyme activities comprising a K56Q and E507K mutation in relation to the wild type DNA polymerase set forth in SEQ ID NO: 1 that is 99.9% identical to SEQ ID NO: 2 and SEQ ID NO: 3[see Abstract; paragraphs 0013-0015; alignment attached as APPENDIX A].
With respect to claim 7, Zhang et al. expression vector comprising the nucleic acid encoding the DNA polymerase [see paragraphs 0019-0020].
With respect to claim 8, Zhang et al. teach a host cell transformed with the expression vector comprising the nucleic acid encoding the DNA polymerase [see paragraph 0023].
With respect to claim 9, Zhang et al. teach a method of producing the DNA polymerase by culturing a host cell transformed with an expression vector comprising the nucleic acid encoding the DNA polymerase mutant and inducing the expression of the DNA polymerase mutant [see paragraph 0024].
With respect to claim 11, Zhang et al. teach a reagent for PCR reaction comprising the DNA polymerase mutant [see paragraphs 0026-0027].
With respect to claim 12, Zhang et al. teach a PCR method comprising performing amplification using the DNA polymerase mutant [see paragraphs 0030-0031].
However, Zhang et al. does not teach the mutant comprising K56Q, A61T, and E507K of claim 1; wherein the hot-start DNA polymerase is a polymerase binding with a Taq antibody, or a DNA polymerase chemically modified by a reagent of claim 3; and wherein the nucleic acid sequence is SEQ ID NO: 3, which represent the triple mutant K56Q, A61T, and E507K of claim 6.
Schafer et al. teach a DNA polymerase mutant comprising at least one mutation selected from A61T and E507K that is relative to a wild type sequence set forth in SEQ ID NO: 1 [see paragraphs 0005-0009; alignment attached as APPENDIX B]. Schafer et al. teach a hot-start DNA polymerase chemically modified by a reagent [see paragraphs 0005-0009, 0093, 0105]. Furthermore, Schafer et al. teach the polymerase is designed to confer advantageous phenotypes under conditions used in industrial and research applications [see Abstract; paragraphs 0005-0009; alignment attached as APPENDIX B].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to arrive at DNA polymerase mutant comprising the amino acid sequence of SEQ ID NO: 2 and nucleic acid sequence of SEQ ID NO: 3 with the teachings of Zhang et al. and Schafer et al. in hand because Zhang et al. identifies K56Q and E507K as advantageous mutants for an improved DNA polymerase. Schafer et al. identifies A61T and E507K as also being advantageous mutant for an improved DNA polymerase. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Zhang et al. and Schafer et al. according to known methods in art to arrive at the claimed invention. 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.
13. Claim 4 is newly rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2020/124481, 06/25/2020; cited on PTO-892 mailed on 04/24/2026 with machine translation attached) in view of Schafer et al. (US 2014/0030765 A1; cited on IDS filed on 06/20/2024) as applied to claims 1, 3, 5-9 and 11-12 above, and further in view of Louwrier et al. (Enzyme and Microbial Technology, 2005; cited on PTO 892 mailed on 04/24/2026). This new grounds of rejection is necessitated by applicants’ amendment to claim 1 to require all three mutations K56Q, A61T, and E507K.
14. The relevant teachings of Zhang et al. and Schafer et al. as applied to claims 1, 3, 5-9, and 11-12 are set forth above.
With respect to claim 4, Schafer et al. teach a hot-start DNA polymerase chemically modified by a reagent [see paragraphs 0005-0009, 0093, 0105].
However, the combination of Zhang et al. and Schafer et al. does not each the hot-start DNA polymerase of claim 4, wherein the reagent for chemical modification is citraconic anhydride.
Louwrier et al. teach that Hot Start PCR can result in the formation of non-specific products when using Taq polymerase and teach that Taq can be modified in a thermally reversible manner via biological methods such as through an antibody or chemically through excess citraconic anhydride [see Abstract; p. 947].
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 Schafer et al. and Louwrier et al. in the Hot-Start polymerase compositions of Schafer et al. to include citraconic anhydride taught by Louwrier et al. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability and would be motivated to combine the teachings of Schafer et al. and Louwrier et al. because Louwrier et al. acknowledges that citraconic anhydride can be used in the combination with Taq polymerase in hot start PCR to prevent nonspecific amplification products. 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
15. Beginning on p. 5 of applicants’ remarks, applicants in summary contend that there is a lack of motivation to arrive at the claimed invention because the impact of mutations on enzyme performance is rarely predictable and given the size of SEQ ID NO: 1, the number of possible single, double and triple mutations is extremely larger. Applicants contend that the person reading the disclosure of Zhang would not be motivated to select the double mutant K56Q and E507K as a starting point for further mutation and Schafer provides no indication that the mutations may provide a beneficial performance in reducing primer dimers. Applicants further contend that the triple mutant as claimed provides a clear improvement in polymerase functionality that cannot have been predicted by the prior art.
These arguments are found to be not persuasive because MPEP 2143 states that “the Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. Examples of rationales that may support a conclusion of obviousness include: (A) combining prior art elements according to known methods to yield predictable results”. Furthermore, MPEP 2144.06 states “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).” In the instant case, as stated above, Zhang et al. identifies K56Q and E507K as advantageous mutants for an improved DNA polymerase. Schafer et al. identifies A61T and E507K as also being advantageous mutant for an improved DNA polymerase. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Zhang et al. and Schafer et al. according to known methods in art to arrive at the claimed invention.
Regarding applicants’ remarks that Zhang et al. teaches away from mutant K56Q/E507K polymerase, 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 particular combination of mutation may have not performed as the best combination, there is no indication in Zhang that the resulting combination would not work as described in the reference and there is no indication in Zhang to discourage said combination.
Regarding applicants’ remarks that the art of record provides no indication that the mutations may provide a beneficial performance in reducing primer dimers, this argument is found to be not persuasive because the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Regarding applicants’ remarks that the triple mutant provides a clear improvement in polymerase functionality that cannot have been predicted by the prior art, this argument is found to be not persuasive because the argument of unexpected results must be commensurate in scope with the claimed invention. MPEP 716.02(d) states “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In the instant case, the alleged unexpected result occurred with a triple mutant Taq polymerase K56Q/A61T/E507K in the amino acid sequence of SEQ ID NO: 1; however, the claim recites “comprises”, which is open and inclusive of additional mutants outside the triple mutants in the claims.
Conclusion
16. Status of the claims:
Claims 1, 3-9 and 11-12 are pending.
Claims 1, 3-9 and 11-12 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.
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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
Zhang et al. with SEQ ID NO: 1
ALIGNMENT:
Query Match 100.0%; Score 4259; Length 832;
Best Local Similarity 100.0%;
Matches 832; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDGD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDGD 60
Qy 61 AVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADD 120
Qy 121 VLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWA 180
Qy 181 DYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPAIREKILAHMDDLK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPAIREKILAHMDDLK 240
Qy 241 LSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWP 300
Qy 301 PPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLA 360
Qy 361 LREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRL 420
Qy 421 EGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGH 480
Qy 481 PFNLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYRELTK 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PFNLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYRELTK 540
Qy 541 LKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIA 600
Qy 601 EEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRR 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 EEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRR 660
Qy 661 AAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYV 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYV 720
Qy 721 ETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARML 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 ETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARML 780
Qy 781 LQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAKE 832
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAKE 832
Zhang et al. with SEQ ID NO: 2
Query Match 99.9%; Score 4255; Length 832;
Best Local Similarity 99.9%;
Matches 831; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALQEDGD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALQEDGD 60
Qy 61 TVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADD 120
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADD 120
Qy 121 VLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWA 180
Qy 181 DYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPAIREKILAHMDDLK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPAIREKILAHMDDLK 240
Qy 241 LSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWP 300
Qy 301 PPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLA 360
Qy 361 LREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRL 420
Qy 421 EGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGH 480
Qy 481 PFNLNSRDQLERVLFDELGLPAIGKTKKTGKRSTSAAVLEALREAHPIVEKILQYRELTK 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PFNLNSRDQLERVLFDELGLPAIGKTKKTGKRSTSAAVLEALREAHPIVEKILQYRELTK 540
Qy 541 LKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIA 600
Qy 601 EEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRR 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 EEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRR 660
Qy 661 AAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYV 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYV 720
Qy 721 ETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARML 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 ETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARML 780
Qy 781 LQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAKE 832
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAKE 832
Zhang et al. with SEQ ID NO: 3
Query Match 99.8%; Score 2494.2; Length 2499;
Best Local Similarity 99.9%;
Matches 2496; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 ATGCGTGGCATGCTGCCGCTGTTCGAGCCGAAGGGTCGTGTGCTGCTGGTTGACGGCCAC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGCGTGGCATGCTGCCGCTGTTCGAGCCGAAGGGTCGTGTGCTGCTGGTTGACGGCCAC 60
Qy 61 CACCTGGCGTACCGTACCTTTCACGCGCTGAAGGGTCTGACCACCAGCCGTGGCGAACCG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CACCTGGCGTACCGTACCTTTCACGCGCTGAAGGGTCTGACCACCAGCCGTGGCGAACCG 120
Qy 121 GTGCAGGCGGTTTATGGTTTCGCGAAAAGCCTGCTGAAGGCGCTGCAAGAGGACGGCGAT 180
||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||
Db 121 GTGCAGGCGGTTTATGGTTTCGCGAAAAGCCTGCTGAAGGCGCTGAAAGAGGACGGCGAT 180
Qy 181 ACGGTGATCGTGGTTTTCGATGCGAAGGCGCCGAGCTTTCGTCACGAAGCGTACGGTGGC 240
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GCGGTGATCGTGGTTTTCGATGCGAAGGCGCCGAGCTTTCGTCACGAAGCGTACGGTGGC 240
Qy 241 TATAAAGCGGGTCGTGCGCCGACCCCGGAGGACTTTCCGCGTCAACTGGCGCTGATTAAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TATAAAGCGGGTCGTGCGCCGACCCCGGAGGACTTTCCGCGTCAACTGGCGCTGATTAAA 300
Qy 301 GAACTGGTTGATCTGCTGGGTCTGGCGCGTCTGGAAGTGCCGGGCTACGAAGCGGACGAT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GAACTGGTTGATCTGCTGGGTCTGGCGCGTCTGGAAGTGCCGGGCTACGAAGCGGACGAT 360
Qy 361 GTTCTGGCGAGCCTGGCGAAGAAAGCGGAGAAGGAAGGTTACGAAGTGCGTATCCTGACC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GTTCTGGCGAGCCTGGCGAAGAAAGCGGAGAAGGAAGGTTACGAAGTGCGTATCCTGACC 420
Qy 421 GCGGACAAAGATCTGTATCAGCTGCTGAGCGACCGTATCCACGTTCTGCACCCGGAGGGT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GCGGACAAAGATCTGTATCAGCTGCTGAGCGACCGTATCCACGTTCTGCACCCGGAGGGT 480
Qy 481 TATCTGATTACCCCGGCGTGGCTGTGGGAAAAGTACGGCCTGCGTCCGGACCAATGGGCG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TATCTGATTACCCCGGCGTGGCTGTGGGAAAAGTACGGCCTGCGTCCGGACCAATGGGCG 540
Qy 541 GATTATCGTGCGCTGACCGGTGACGAGAGCGATAACCTGCCGGGCGTTAAAGGTATTGGC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GATTATCGTGCGCTGACCGGTGACGAGAGCGATAACCTGCCGGGCGTTAAAGGTATTGGC 600
Qy 601 GAAAAAACCGCGCGTAAGCTGCTGGAGGAATGGGGTAGCCTGGAAGCGCTGCTGAAAAAC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GAAAAAACCGCGCGTAAGCTGCTGGAGGAATGGGGTAGCCTGGAAGCGCTGCTGAAAAAC 660
Qy 661 CTGGATCGTCTGAAGCCGGCGATCCGTGAGAAAATTCTGGCGCACATGGACGATCTGAAG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 CTGGATCGTCTGAAGCCGGCGATCCGTGAGAAAATTCTGGCGCACATGGACGATCTGAAG 720
Qy 721 CTGAGCTGGGACCTGGCGAAAGTGCGTACCGACCTGCCGCTGGAAGTGGATTTCGCGAAG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 CTGAGCTGGGACCTGGCGAAAGTGCGTACCGACCTGCCGCTGGAAGTGGATTTCGCGAAG 780
Qy 781 CGTCGTGAGCCGGATCGTGAACGTCTGCGTGCGTTCCTGGAGCGTCTGGAATTTGGTAGC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 CGTCGTGAGCCGGATCGTGAACGTCTGCGTGCGTTCCTGGAGCGTCTGGAATTTGGTAGC 840
Qy 841 CTGCTGCACGAGTTTGGCCTGCTGGAAAGCCCGAAGGCGCTGGAGGAAGCGCCGTGGCCG 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 CTGCTGCACGAGTTTGGCCTGCTGGAAAGCCCGAAGGCGCTGGAGGAAGCGCCGTGGCCG 900
Qy 901 CCGCCAGAGGGTGCGTTCGTGGGCTTTGTTCTGAGCCGTAAAGAACCGATGTGGGCGGAC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CCGCCAGAGGGTGCGTTCGTGGGCTTTGTTCTGAGCCGTAAAGAACCGATGTGGGCGGAC 960
Qy 961 CTGCTGGCGCTGGCGGCGGCGCGTGGTGGCCGTGTGCACCGTGCGCCGGAGCCGTACAAG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CTGCTGGCGCTGGCGGCGGCGCGTGGTGGCCGTGTGCACCGTGCGCCGGAGCCGTACAAG 1020
Qy 1021 GCGCTGCGTGACCTGAAAGAAGCGCGTGGTCTGCTGGCGAAAGATCTGAGCGTTCTGGCG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GCGCTGCGTGACCTGAAAGAAGCGCGTGGTCTGCTGGCGAAAGATCTGAGCGTTCTGGCG 1080
Qy 1081 CTGCGCGAAGGTCTGGGTCTGCCGCCGGGTGACGATCCGATGCTGCTGGCGTACCTGCTG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 CTGCGCGAAGGTCTGGGTCTGCCGCCGGGTGACGATCCGATGCTGCTGGCGTACCTGCTG 1140
Qy 1141 GATCCGAGCAACACCACCCCGGAGGGTGTGGCGCGTCGTTATGGTGGCGAATGGACCGAG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GATCCGAGCAACACCACCCCGGAGGGTGTGGCGCGTCGTTATGGTGGCGAATGGACCGAG 1200
Qy 1201 GAAGCGGGCGAGCGTGCGGCGCTGAGCGAACGTCTGTTCGCGAACCTGTGGGGTCGTCTG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GAAGCGGGCGAGCGTGCGGCGCTGAGCGAACGTCTGTTCGCGAACCTGTGGGGTCGTCTG 1260
Qy 1261 GAGGGCGAGGAACGTCTGCTGTGGCTGTACCGTGAGGTGGAACGTCCGCTGAGCGCGGTT 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GAGGGCGAGGAACGTCTGCTGTGGCTGTACCGTGAGGTGGAACGTCCGCTGAGCGCGGTT 1320
Qy 1321 CTGGCGCACATGGAAGCGACCGGTGTGCGTCTGGACGTTGCGTATCTGCGTGCGCTGAGC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 CTGGCGCACATGGAAGCGACCGGTGTGCGTCTGGACGTTGCGTATCTGCGTGCGCTGAGC 1380
Qy 1381 CTGGAAGTGGCGGAGGAAATCGCGCGTCTGGAGGCGGAAGTTTTCCGTCTGGCGGGCCAC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CTGGAAGTGGCGGAGGAAATCGCGCGTCTGGAGGCGGAAGTTTTCCGTCTGGCGGGCCAC 1440
Qy 1441 CCGTTTAACCTGAACAGCCGTGACCAGCTGGAGCGTGTTCTGTTTGATGAACTGGGTCTG 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 CCGTTTAACCTGAACAGCCGTGACCAGCTGGAGCGTGTTCTGTTTGATGAACTGGGTCTG 1500
Qy 1501 CCGGCGATTGGCAAGACCAAAAAAACCGGCAAGCGTAGCACCAGCGCGGCGGTGCTGGAG 1560
|||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||
Db 1501 CCGGCGATTGGCAAGACCGAAAAAACCGGCAAGCGTAGCACCAGCGCGGCGGTGCTGGAG 1560
Qy 1561 GCGCTGCGTGAAGCGCACCCGATCGTTGAGAAGATTCTGCAGTACCGTGAACTGACCAAG 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 GCGCTGCGTGAAGCGCACCCGATCGTTGAGAAGATTCTGCAGTACCGTGAACTGACCAAG 1620
Qy 1621 CTGAAAAGCACCTATATCGACCCGCTGCCGGATCTGATTCACCCGCGTACCGGTCGTCTG 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 CTGAAAAGCACCTATATCGACCCGCTGCCGGATCTGATTCACCCGCGTACCGGTCGTCTG 1680
Qy 1681 CACACCCGTTTCAACCAAACCGCGACCGCGACCGGTCGTCTGAGCAGCAGCGACCCGAAC 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 CACACCCGTTTCAACCAAACCGCGACCGCGACCGGTCGTCTGAGCAGCAGCGACCCGAAC 1740
Qy 1741 CTGCAGAACATCCCGGTGCGTACCCCGCTGGGTCAACGTATCCGTCGTGCGTTTATTGCG 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 CTGCAGAACATCCCGGTGCGTACCCCGCTGGGTCAACGTATCCGTCGTGCGTTTATTGCG 1800
Qy 1801 GAGGAAGGCTGGCTGCTGGTTGCGCTGGATTACAGCCAGATTGAGCTGCGTGTTCTGGCG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 GAGGAAGGCTGGCTGCTGGTTGCGCTGGATTACAGCCAGATTGAGCTGCGTGTTCTGGCG 1860
Qy 1861 CACCTGAGCGGTGACGAAAACCTGATCCGTGTTTTCCAAGAGGGCCGTGATATTCACACC 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 CACCTGAGCGGTGACGAAAACCTGATCCGTGTTTTCCAAGAGGGCCGTGATATTCACACC 1920
Qy 1921 GAAACCGCGAGCTGGATGTTTGGTGTGCCGCGTGAGGCGGTTGACCCGCTGATGCGTCGT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 GAAACCGCGAGCTGGATGTTTGGTGTGCCGCGTGAGGCGGTTGACCCGCTGATGCGTCGT 1980
Qy 1981 GCGGCGAAGACCATCAACTTCGGTGTGCTGTATGGCATGAGCGCGCACCGTCTGAGCCAG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 GCGGCGAAGACCATCAACTTCGGTGTGCTGTATGGCATGAGCGCGCACCGTCTGAGCCAG 2040
Qy 2041 GAGCTGGCGATCCCGTACGAGGAAGCGCAGGCGTTTATTGAACGTTATTTCCAAAGCTTT 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 GAGCTGGCGATCCCGTACGAGGAAGCGCAGGCGTTTATTGAACGTTATTTCCAAAGCTTT 2100
Qy 2101 CCGAAGGTTCGTGCGTGGATTGAGAAAACCCTGGAGGAAGGTCGTCGTCGTGGTTACGTG 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 CCGAAGGTTCGTGCGTGGATTGAGAAAACCCTGGAGGAAGGTCGTCGTCGTGGTTACGTG 2160
Qy 2161 GAAACCCTGTTCGGTCGTCGTCGTTACGTTCCGGATCTGGAGGCGCGTGTGAAAAGCGTT 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 GAAACCCTGTTCGGTCGTCGTCGTTACGTTCCGGATCTGGAGGCGCGTGTGAAAAGCGTT 2220
Qy 2221 CGTGAGGCGGCGGAACGTATGGCGTTCAACATGCCGGTGCAGGGTACCGCGGCGGACCTG 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 CGTGAGGCGGCGGAACGTATGGCGTTCAACATGCCGGTGCAGGGTACCGCGGCGGACCTG 2280
Qy 2281 ATGAAACTGGCGATGGTTAAGCTGTTTCCGCGTCTGGAGGAAATGGGCGCGCGTATGCTG 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 ATGAAACTGGCGATGGTTAAGCTGTTTCCGCGTCTGGAGGAAATGGGCGCGCGTATGCTG 2340
Qy 2341 CTGCAAGTGCACGATGAGCTGGTTCTGGAAGCGCCGAAGGAGCGTGCGGAAGCGGTGGCG 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 CTGCAAGTGCACGATGAGCTGGTTCTGGAAGCGCCGAAGGAGCGTGCGGAAGCGGTGGCG 2400
Qy 2401 CGTCTGGCGAAAGAGGTGATGGAAGGTGTTTACCCGCTGGCGGTTCCGCTGGAAGTTGAG 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 CGTCTGGCGAAAGAGGTGATGGAAGGTGTTTACCCGCTGGCGGTTCCGCTGGAAGTTGAG 2460
Qy 2461 GTGGGTATCGGCGAGGACTGGCTGAGCGCGAAAGAATAA 2499
|||||||||||||||||||||||||||||||||||||||
Db 2461 GTGGGTATCGGCGAGGACTGGCTGAGCGCGAAAGAATAA 2499
APPENDIX B
Schafer et al. with SEQ ID NO: 1
Query Match 100.0%; Score 4259; Length 832;
Best Local Similarity 100.0%;
Matches 832; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDGD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDGD 60
Qy 61 AVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADD 120
Qy 121 VLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWA 180
Qy 181 DYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPAIREKILAHMDDLK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPAIREKILAHMDDLK 240
Qy 241 LSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWP 300
Qy 301 PPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLA 360
Qy 361 LREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRL 420
Qy 421 EGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGH 480
Qy 481 PFNLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYRELTK 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PFNLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYRELTK 540
Qy 541 LKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIA 600
Qy 601 EEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRR 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 EEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRR 660
Qy 661 AAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYV 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYV 720
Qy 721 ETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARML 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 ETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARML 780
Qy 781 LQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAKE 832
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAKE 832
Prosecution Insights