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 12/02/2025 in response to the Non-Final Rejection mailed on 09/05/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-25, 27 and 30-36 are pending.
4. Claims 9-16, 18 and 20-25 stand withdrawn pursuant to 37 CFR 1.142(b).
5. Applicant’s remarks filed on 12/02/2025 in response to the Non-Final Rejection mailed on 09/05/2025 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of claim 27 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for lack of antecedent basis is withdrawn in view of applicants’ amendment to claim 27 to depend upon claim 1.
Claim Rejections - 35 USC § 102
7. The rejection of claims 2-3 under 35 U.S.C. 102(a)(2) as being anticipated by Yu et al. (WO 2021/194909 A1, priority to 03/21/2020; cited on PTO-892 mailed on 09/05/2025) is withdrawn in view of applicants’ amendment to claims 2-3. Yu et al. does not teach or suggest at least two amino acid substitutions or the combination of mutations as claimed in amended claims 2-3.
8. The rejection of claims 1-8, 17, 19, 27, and 30-36 under 35 U.S.C. 102(a)(2) as being anticipated by Lai et al. (WO 2021/203098 A2, priority to 04/03/2020; cited on PTO-892 mailed on 09/05/2025) is withdrawn in view of applicants’ amendment to the claims. Lai et al. does not teach or suggest the specific point mutations or combinations of mutations as claimed in claims 1-3.
9. The rejection of claims 1, 4, 6-8, 17, 19, 27, and 31-36 under 35 U.S.C. 102(a)(2) as being anticipated by Yu et al. (WO 2021/194909 A1, priority to 03/21/2020; cited on PTO-892 mailed on 09/05/2025) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims.
10. As amended, claims 1, 4, 27, 31, and 34 are drawn to a recombinant ACE2 polypeptide comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2 or 3 and comprising at least one amino acid residue substitutions selected from the group consisting of Q18R, K31Y, N33S, H34I, F40L, F40S, N49D, N49S, N51S, N53S, E57G, N61D, M62T, M62I, M62V, N64D, K68R, W69R, W69V, W69K, W69I, L100P, Q101R, wherein the residues are numbered with reference to SEQ ID NO: 1.
Claims 6-8, 32, and 35 are drawn to a fusion protein comprising the recombinant ACE2 polypeptide of claim 1 fused to a dimerization domain.
Claims 17, 33, and 36 are drawn to a composition comprising a dimer of the recombinant ACE2 polyeptide of claim 1.
Claim 19 is drawn to a pharmaceutical preparation comprising: the recombinant ACE2 polypeptide of claim 1 or the fusion protein of claim 6; and a pharmaceutically acceptable carrier.
Claim 30 is drawn to a composition comprising the fusion protein of claim 1.
11. With respect to claim 1, Yu et al. teach a recombinant ACE2 polypeptide comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 2 and 3 and wherein at least one amino acid residue substitutions selected from H34I with reference to SEQ ID NO: 1 [see Abstract; paragraphs 023-024; 065; 0066; 0105; alignments attached as APPENDIX A].
With respect to claim 4, Yu et al. teach the recombinant ACE2 polypeptide comprising substitutions H374N and H378N [see paragraph 0101].
With respect to claim 6, Yu et al. teach a fusion protein comprising the recombinant ACE2 polypeptide fused to an Fc domain (dimerization domain) [see paragraph 065].
With respect to claim 7, Yu et al. teach the fusion protein wherein the recombinant ACE2 polypeptide is fused to the dimerization domain via a peptide linker [see paragraph 041].
With respect to claim 8, Yu et al. teach the fusion protein wherein the dimerization domain comprises an Fc domain [see paragraph 065].
With respect to claim 17, Yu et al. teach compositions comprising a dimer of the recombinant ACE2 polypeptide [see paragraph 046].
With respect to claim 19, Yu et al. teach a pharmaceutical composition comprising the recombinant ACE2 polypeptide and a pharmaceutically acceptable carrier [see paragraph 095].
With respect to claims 27 and 31-33, Yu et al. teach the recombinant ACE2 polypeptide has increased binding affinity for the SARS-CoV-2 spike protein as compared to wild type [see paragraph 024]. Although Yu et al. does not explicitly teach that that the affinity is more than 180-fold, Yu et al. does teach identical structures as claimed. To this end, it is the examiner’s position that this feature would be inherent to the ACE2 polypeptides of Yu et al. Since the Office does not have the facilities for examining and comparing applicants’ protein with the protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the protein of the prior art does not possess the same material structural and functional characteristics of the claimed protein). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 30, Yu et al. teach compositions comprising the fusion protein of the recombinant ACE2 polypeptide [see paragraph 046].
With respect to claims 34-36, Yu et al. teach the recombinant ACE2 polypeptide has increased binding affinity for the SARS-CoV-2 spike protein as compared to wild type [see paragraph 024]. Although Yu et al. does not explicitly teach that that the neutralization efficacy is greater than 25-fold of wild type, Yu et al. does teach identical structures as claimed. To this end, it is the examiner’s position that this feature would be inherent to the ACE2 polypeptides of Yu et al. Since the Office does not have the facilities for examining and comparing applicants’ protein with the protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the protein of the prior art does not possess the same material structural and functional characteristics of the claimed protein). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
RESPONSE TO REMARKS: Beginning on p. 8 of applicants’ remarks, applicants in summary contend that Yu et al. does not disclose any of the substitutions as claimed.
This argument is found to be not persuasive in view of the modified rejection set forth above.
12. The rejection of claims 1-3, 6-8, 17, 19, 27, and 30-36 under 35 U.S.C. 102(a)(2) as being anticipated by Malik et al. (WO 2021/188576 A1, priority to 03/16/2020; cited on PTO-892 mailed on 09/05/2025) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims.
13. With respect to claim 1, Malik et al. teach a recombinant ACE2 polypeptide comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2 and SEQ ID NO: 3 with amino acid residue substitutions K31Y and W69V [see Abstract; p. 21-24; Tables 1-2; Claims; alignment attached as APPENDIX B].
With respect to claim 2, Malik et al. teach a recombinant ACE2 polypeptide comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2 and SEQ ID NO: 3 with amino acid residue substitutions K31Y and W69V [see Abstract; p. 21-24; Tables 1-2; Claims; alignment attached as APPENDIX B].
With respect to claim 3, Malik et al. teach a recombinant ACE2 polypeptide comprising comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2 and SEQ ID NO: 3 with amino acid residue substitutions H34V and N90Q [see Abstract; p. 21-24; Tables 1-2; Claims; alignment attached as APPENDIX B].
With respect to claim 6, Malik et al. teach a fusion protein comprising the recombinant ACE2 polypeptide fused to a dimerization domain [see p. 7, lines 6-10].
With respect to claim 7, Malik et al. teach the fusion protein wherein the ACE2 polypeptide is fused to the dimerization domain via a peptide linker [see Example 3].
With respect to claim 8, Malik et al. teach the fusion protein wherein the dimerization domain is an Fc domain [see p. 35, lines 5-10].
With respect to claim 17, Malik et al. teach a composition comprising a dimer of the recombinant ACE2 polypeptide [see p. 18, top].
With respect to claim 19, Malik et al. teach a pharmaceutical preparation comprising a recombinant ACE2 polypeptide and a pharmaceutically acceptable carrier [see p. 17, bottom to top of p. 18].
With respect to claims 27 and 31-33, Malik et al. teach the recombinant ACE2 polypeptide having a higher fold affinity for SARS-CoV-2 spike protein [Abstract; p. 6-7; p. 21-24; Tables 1-2; Claims]. Although Malik et al. does not explicitly teach that that the affinity is more than 180-fold, Malik et al. does teach identical structures as claimed. To this end, it is the examiner’s position that this feature would be inherent to the ACE2 polypeptides of Malik et al. Since the Office does not have the facilities for examining and comparing applicants’ protein with the protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the protein of the prior art does not possess the same material structural and functional characteristics of the claimed protein). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 30, Malik et al. teach compositions comprising the fusion protein of the recombinant ACE2 polypeptide [see p. 18, top].
With respect to claims 34-36, Malik et al. teach the recombinant ACE2 polypeptide has increased binding affinity for the SARS-CoV-2 spike protein as compared to wild type [see Abstract; p. 6-7; p. 21-24; Tables 1-2; Claims]. Although Malik et al. does not explicitly teach that that the neutralization efficacy is greater than 25-fold of wild type, Malik et al. does teach identical structures as claimed. To this end, it is the examiner’s position that this feature would be inherent to the ACE2 polypeptides of Malik et al. Since the Office does not have the facilities for examining and comparing applicants’ protein with the protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the protein of the prior art does not possess the same material structural and functional characteristics of the claimed protein). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
RESPONSE TO REMARKS: Beginning on p. 9 of applicants’ remarks, applicants contend that Malik et al. fails to teach any of the amino acid substitutions.
This argument is found to be not persuasive in view of the modified rejection set forth above.
Claim Rejections - 35 USC § 103
14. 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.
15. Claim(s) 5 is/are newly rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (WO 2021/194909 A1, priority to 03/21/2020; cited on PTO-892 mailed on 09/05/2025) in view of Lai et al. (WO 2021/203098 A2, priority to 04/03/2020; cited on PTO-892 mailed on 09/05/2025). This new grounds of rejection is necessitated by applicants’ amendment to the claims.
16. The relevant teachings of Yu et al. as applied to claims 1, 4, 6-8, 17, 19, 27, and 31-36 are set forth in the 102(a)(2) rejection above.
However, Yu et al. does not teach the recombinant ACE2 polypeptide of claim 5, wherein the soluble ACE2 receptor ectodomain polypeptide comprises amino acid residue substitution H345L.
Lai et al. teach a recombinant ACE2 polypeptide comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence having 99% sequence identity to SEQ ID NO: 3 and amino acid substitution H345L, wherein the variants are useful against ACE-2 targeted viruses [see Abstract; paragraph 000136; alignment attached as APPENDIX C].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to include a H345L mutation in the ACE2 polypeptide variants of Yu et al. because Yu et al. teach ACE2 polypeptide variants useful in therapeutic treatment of viral diseases. Lai et al. teach similar variants of ACE2 having a H345L mutation that are useful against ACE-2 targeted viruses. 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 Yu et al. and Lai et al. because Lai et al. acknowledges this variant is useful in the treatment of ACE2 targeted viruses. 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.
17. Claim 5 is newly rejected under 35 U.S.C. 103 as being unpatentable over Malik et al. (WO 2021/188576 A1, priority to 03/16/2020; cited on PTO-892 mailed on 09/05/2025) in view of Lai et al. (WO 2021/203098 A2, priority to 04/03/2020; cited on PTO-892 mailed on 09/05/2025). This new grounds of rejection is necessitated by applicants’ amendment to the claims.
16. The relevant teachings of Malik et al. as applied to claims 1-3, 6-8, 17, 19, 27, and 30-36 are set forth in the 102(a)(2) rejection above.
However, Malik et al. does not teach the recombinant ACE2 polypeptide of claim 5, wherein the soluble ACE2 receptor ectodomain polypeptide comprises amino acid residue substitution H345L.
Lai et al. teach a recombinant ACE2 polypeptide comprising a soluble ACE2 receptor ectodomain polypeptide comprising an amino acid sequence having 99% sequence identity to SEQ ID NO: 3 and amino acid substitution H345L, wherein the variants are useful against ACE-2 targeted viruses [see Abstract; paragraph 000136; alignment attached as APPENDIX C].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to include a H345L mutation in the ACE2 polypeptide variants of Malik et al. because Malik et al. teach ACE2 polypeptide variants useful in therapeutic treatment of viral diseases. Lai et al. teach similar variants of ACE2 having a H345L mutation that are useful against ACE-2 targeted viruses. 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 Malik et al. and Lai et al. because Lai et al. acknowledges this variant is useful in the treatment of ACE2 targeted viruses. 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
19. Status of the claims:
Claims 1-25, 27 and 30-36 are pending.
Claims 9-16, 18 and 20-25 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1-8, 17, 19, 27, and 30-36 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.
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
Yu et al. with SEQ ID NO: 2
Query Match 100.0%; Score 3882; DB 1; Length 723;
Best Local Similarity 100.0%;
Matches 723; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 360
Qy 361 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
Qy 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
Qy 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
Qy 721 PVS 723
|||
Db 721 PVS 723
Yu et al. with SEQ ID NO: 3
Query Match 100.0%; Score 3240; DB 1; Length 723;
Best Local Similarity 100.0%;
Matches 597; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 360
Qy 361 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYA 597
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYA 597
Yu et al. with SEQ ID NO: 1
Query Match 90.5%; Score 3882; DB 1; Length 723;
Best Local Similarity 100.0%;
Matches 723; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 18 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 77
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 78 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 137
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 138 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 197
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 198 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 257
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 258 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 317
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 318 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 377
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 360
Qy 378 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 437
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 438 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 497
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 498 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 557
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 558 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 617
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
Qy 618 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 677
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
Qy 678 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 737
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
Qy 738 PVS 740
|||
Db 721 PVS 723
APPENDIX B
Malik et al. with SEQ ID NO: 2
Query Match 98.1%; Score 3810; DB 1; Length 714;
Best Local Similarity 99.6%;
Matches 711; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 2 STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQST 61
|||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 STIEEQAKYFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQST 60
Qy 62 LAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNP 121
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNP 120
Qy 122 QECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYED 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYED 180
Qy 182 YGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISP 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISP 240
Qy 242 IGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSV 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 IGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSV 300
Qy 302 GLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGH 361
||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GLPNMTQGFWEYSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGH 360
Qy 362 IQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINF 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 IQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINF 420
Qy 422 LLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYC 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYC 480
Qy 482 DPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNML 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 DPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNML 540
Qy 542 RLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSI 601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 RLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSI 600
Qy 602 KVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPR 661
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 KVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPR 660
Qy 662 ISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLG 715
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 ISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLG 714
Malik et al. with SEQ ID NO: 3
Query Match 99.2%; Score 3215; DB 1; Length 714;
Best Local Similarity 99.5%;
Matches 593; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 2 STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQST 61
|||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 STIEEQAKYFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQST 60
Qy 62 LAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNP 121
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNP 120
Qy 122 QECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYED 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYED 180
Qy 182 YGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISP 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISP 240
Qy 242 IGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSV 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 IGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSV 300
Qy 302 GLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGH 361
||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GLPNMTQGFWEYSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGH 360
Qy 362 IQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINF 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 IQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINF 420
Qy 422 LLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYC 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYC 480
Qy 482 DPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNML 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 DPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNML 540
Qy 542 RLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYA 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 RLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYA 596
APPENDIX C
Lai et al. with SEQ ID NO: 3
Query Match 99.6%; Score 3226; DB 1; Length 598;
Best Local Similarity 99.7%;
Matches 595; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||:|||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHNEMG 360
Qy 361 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYA 597
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYA 597