DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 4, 7, 10, 15, 18, 20, 22, 24, 30, 33-34, 39, 41, 44, 49, 51, 58, 60 and 68 are pending in the present application.
Applicant’s election of Group I, drawn to a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker, and a nuclease deficient RNA-guided DNA endonuclease enzyme, wherein the demethylation domain is a TET1 domain, a TET 2 domain, a TET3 domain, or a combination of two or more thereof, in the reply filed on 11/17/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant also elected the following species: (i) TET1 as a species of a demethylation domain; (ii) dCas9 as a species of a nuclease deficient RNA-guided DNA endonuclease enzyme; (iii) SEQ ID NO: 5 as a species of an XTEN linker; and (iv) SEQ ID NO:112 as a species of a fusion protein.
In addition to the elected dCas9, the examiner also examines a nuclease-deficient DNA endonuclease enzyme which is inadvertently not restricted in the Restriction Requirement dated 7/17/2025.
Accordingly, claims 10, 15, 18, 20, 24, 33-34, 39, 41, 44, 58 and 68 were withdrawn from further considerations because they are directed to non-elected inventions.
Therefore, claims 1, 4, 7, 22, 30, 49, 51 and 60 are examined on the merits herein with the above elected species along with a nuclease-deficient DNA endonuclease enzyme.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 22, 49 and 60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
I. A fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker, and a nuclease-deficient RNA-guided DNA endonuclease enzyme, wherein the demethylation domain is a TET1 domain, a TET2 domain, a TET3 domain, or a combination of two or more thereof;
II. A fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker, and a nuclease-deficient DNA endonuclease enzyme, wherein the demethylation domain is a TET1 domain, a TET2 domain, a TET3 domain, or a combination of two or more thereof; and wherein the nuclease-deficient DNA endonuclease enzyme is a zinc finger domain or a TALE;
does not reasonably provide enablement for a fusion protein comprising from N-terminus to C-terminus any other demethylation domain, an XTEN linker, and a nuclease-deficient RNA-guided DNA endonuclease enzyme or any other nuclease-deficient DNA endonuclease enzyme as encompassed broadly by the instant claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in the determination of an enabling disclosure have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art and the breadth of the claims. Ex parte Forman, (230 USPQ 546 (Bd Pat. Appl & Unt, 1986); In re Wands, 858 F.2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988)).
When read in light of the present specification, the sole purpose for the claimed fusion proteins is to reactivate a silenced target nucleic acid sequence in a cell (see at least Brief Summary). The instant specification is not enabled for the instant broadly claimed invention for the reasons discussed below.
1. The breadth of the claims
Claim 22 encompasses a fusion protein comprising from N-terminus to C-terminus, any demethylation domain not necessarily limited to the family of TET proteins, an XTEN linker, and a nuclease-deficient RNA-guided DNA endonuclease enzyme.
Claim 49 encompasses a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker, and any nuclease-deficient DNA endonuclease enzyme (e.g., a nuclease-deficient zinc finger nuclease, a nuclease-deficient TALEN, any nuclease-deficient restriction enzymes, a nuclease-deficient DNase I, a nuclease-deficient micrococcal nuclease, or a nuclease-deficient mung bean nuclease), wherein the demethylation domain is a TET1 domain, a TET2 domain, a TET3 domain, or a combination of two or more thereof.
Claim 60 encompasses a fusion protein comprising from N-terminus to C-terminus, any demethylation domain not necessarily limited to the family of TET proteins, an XTEN linker, and any nuclease-deficient DNA endonuclease enzyme (e.g., a nuclease-deficient zinc finger nuclease, a nuclease-deficient TALEN, any nuclease-deficient restriction enzymes, a nuclease-deficient DNase I, a nuclease-deficient micrococcal nuclease, or a nuclease-deficient mung bean nuclease).
2. The state and the unpredictability of the prior art
Before the effective filing date of the present application (06/05/2020), little was known about a fusion protein comprising from N-terminus to C-terminus, any demethylation domain, an XTEN linker, and a nuclease-deficient RNA-guided DNA endonuclease enzyme or any nuclease-deficient DNA endonuclease enzyme of the presently claimed invention as evidenced at least by the teachings of Jacobsen et al (US 2019/0352654; IDS), Cheng et al (US 11,780,895), Rao et al (US 9,115386) and Khalil (Journal of Genetic Engineering and Biotechnology 18:68; 2020). Cheng et al stated “Demethylation pathways, which remove the methyl group to restore unmethylated DNA, involve the ten-eleven translocation (TET) family of proteins. These are TET methylcytosine dioxygenases that catalyze the initial and critical step leading to replacing 5mC with unmethylated cytosine” (col. 1, lines 57-62). Moreover, the physiological art is already recognized as unpredictable (MPEP 2164.03).
3. The amount of direction or guidance provided
Apart from disclosing Ten-eleven translocation (TET) enzymes or functional domains of TET enzymes to be used as “demethylation domains”, along with a zinc finger domain and a TALE to be used as a “nuclease-deficient endonuclease enzyme” (see at least paragraphs [0089]-[0093], [0132]; and Examples); the instant specification failed to provide sufficient guidance for an ordinary skilled artisan on how to make and use a fusion protein comprising any other demethylation domain and/or any other nuclease-deficient DNA endonuclease enzyme, particularly for demethylation and reactivation of any silenced target nucleic acid sequence in a cell as encompassed broadly by the instant claims. For example, apart from TET enzymes or functional domains of the TET enzymes, what are the specific structures of the non-TET domains that function as a demethylation domain in the claimed fusion proteins? Cheng et al only taught that the ten-eleven translocation (TET) family of proteins are TET methylcytosine dioxygenases that catalyze the initial and critical step leading to replacing 5mC with unmethylated cytosine. Similarly, apart from a zinc finger domain and a TALE, what are the specific structures possessed by other nuclease-deficient DNA endonuclease enzymes such as any nuclease-deficient restriction enzymes, a nuclease-deficient DNase I, a nuclease-deficient micrococcal nuclease, and a nuclease-deficient mung bean nuclease to be used in the claimed fusion proteins for demethylation and reactivation of any silenced target nucleic acid sequence in a cell? Even in the December 2020 review of Khalil, he only disclosed 4 types of “programmable” nucleases (meganucleases, zinc finger nucleases, transcription activator-like effector nucleases, and the CRISPR-Cas9 system) that are available for genome editing; and with respect to meganucleases Khalil further stated “[e]ach new genome engineering target requires an initial protein engineering step to produce a custom MegN. Thus, in spite of the so many available MegNs, the probability of finding an enzyme that targets a desired locus is very small and the production of customized MegNs remains really complex and highly inefficient. Therefore, routine applications of MegNs in genome editing is limited and proved technically challenging to work with”. There is also no evidence of record indicating or suggesting that any nuclease-deficient meganuclease has been engineered in the form of a fusion protein of the present application for demethylation and reactivation of any silenced target nucleic acid sequence in a cell.
Since the prior art before the effective filing date of the present application failed to provide sufficient guidance regarding to the aforementioned issues, it is incumbent upon the present application to do so. Given the state of the prior art, coupled with the lack of sufficient guidance provided by the present application, it would have required undue experimentation for a skilled artisan to make and use the instant invention as claimed broadly.
As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires:
That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.
Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maizel.).
Accordingly, due to the lack of sufficient guidance provided by the specification regarding to the issues set forth above, the state and unpredictability of the relevant art, and the breadth of the instant claims, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4, 7, 22, 49, 51 and 60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jacobsen et al (US 2019/0352654; IDS).
The instant claims are directed to a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker (e.g., the elected SEQ ID NO: 5), and a nuclease-deficient RNA-guided DNA endonuclease (e.g., the elected dCas9) or a nuclease-deficient DNA endonuclease enzyme (e.g., a zinc finger nuclease or a TALE), wherein the demethylation is a TET1 domain (e.g., the elected SEQ ID NO: 1), a TET2 domain, a TET3 domain, or a combination of two or more thereof.
With respect to the elected species, Jacobsen et al already disclosed at least a recombinant protein for inducing epigenetic modification at specific locus or a targeted gene demethylation, wherein the recombinant protein comprises: a DNA binding domain and a TET1 polypeptide or a fragment thereof; and wherein the DNA binding domain includes a zinc finger domain comprising three, four, five, six, seven, eight or nine zinc fingers; a TALE effector targeting domain; and a nuclease-deficient Cas9 polypeptide or dCas9 (Abstract; and Brief Summary; particularly paragraphs [0007], [0010], [0097]-[0103], [0110]-[00116], [0122]-[0126] and [0145]). Jacobsen et al stated clearly “The TET polypeptide (e.g. TET1 polypeptide) portion of a TET-like protein (e.g. TET1-like protein) may be present in various N-terminal or C-terminal orientations relative to the heterologous coding sequence present in a TET-like protein (e.g. TET1-like protein” (last sentence in paragraph [0103]); “In some embodiments, a recombinant protein of the present disclosure further contains two N-terminal CCCH zinc-finger domains” (paragraph [0113]); and “In some embodiments, the TET-dCAS9 fusion (e.g. TET1-dCAS9 fusion) is a direct fusion. In some embodiments, the TET-dCAS9 fusion (e.g. TET1-CAS9 fusion) is an indirection fusion)” (last sentence of paragraph [0145]). Jacobsen et al specifically taught that various linkers may be used in the construction of recombinant proteins, and specifically stated “The XTEN linker, SGSETPGTSESATPES (SEQ ID NO: 166), and variants thereof, described in Guilinget et al, 2014 (Nature Biotechnology 32, 577-582), may also be used. This particular linker was previously shown to produce the best results among other linkers in a protein fusion between dCAS9 and the nuclease Fok1” (last two sentences of paragraph [0141]). The XTEN linker with the sequence SGSETPGTSESATPES is 100% identical to SEQ ID NO: 5 of the present application. Jacobsen et al further disclosed that suitable TET1 proteins include those listed in Table 1 such as the human TET1 protein of SEQ ID NO: 1 that is 100% identical to SEQ ID NO: 1 of the present application (paragraph [0185]), Table 1; and attached sequence search below).
Since Jacobsen et al taught that various linkers can be used in the construction of recombinant proteins, particularly the XTEN linker with the sequence of SGSETPGTSESATPES, and specifically that an exemplary TET1-CAS9 fusion is an indirect fusion protein; an ordinary skill in the art would readily recognize the teachings of Jacobsen et al include a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker, and a nuclease-deficient RNA-guided DNA endonuclease (e.g., dCas9) or a nuclease-deficient DNA endonuclease enzyme (e.g., a zinc finger nuclease or a TALE), wherein the demethylation is a TET1 domain.
Accordingly, the teachings of Jacobsen et al meet every limitation of the instant claims. Therefore, the reference anticipates the instant claims.
Claim Rejections - 35 USC § 103
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.
Alternatively, claims 1, 4, 7, 22, 49, 51 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Jacobsen et al (US 2019/0352654; IDS).
The instant claims are directed to a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker (e.g., the elected SEQ ID NO: 5), and a nuclease-deficient RNA-guided DNA endonuclease (e.g., the elected dCas9) or a nuclease-deficient DNA endonuclease enzyme (e.g., a zinc finger nuclease or a TALE), wherein the demethylation is a TET1 domain (e.g., the elected SEQ ID NO: 1), a TET2 domain, a TET3 domain, or a combination of two or more thereof.
With respect to the elected species, Jacobsen et al already disclosed at least a recombinant protein for inducing epigenetic modification at specific locus or a targeted gene demethylation, wherein the recombinant protein comprises: a DNA binding domain and a TET1 polypeptide or a fragment thereof; and wherein the DNA binding domain includes a zinc finger domain comprising three, four, five, six, seven, eight or nine zinc fingers; a TALE effector targeting domain; and a nuclease-deficient Cas9 polypeptide or dCas9 (Abstract; and Brief Summary; particularly paragraphs [0007], [0010], [0097]-[0103], [0110]-[00116], [0122]-[0126] and [0145]). Jacobsen et al stated clearly “The TET polypeptide (e.g. TET1 polypeptide) portion of a TET-like protein (e.g. TET1-like protein) may be present in various N-terminal or C-terminal orientations relative to the heterologous coding sequence present in a TET-like protein (e.g. TET1-like protein” (last sentence in paragraph [0103]); “In some embodiments, a recombinant protein of the present disclosure further contains two N-terminal CCCH zinc-finger domains” (paragraph [0113]); and “In some embodiments, the TET-dCAS9 fusion (e.g. TET1-dCAS9 fusion) is a direct fusion. In some embodiments, the TET-dCAS9 fusion (e.g. TET1-CAS9 fusion) is an indirection fusion)” (last sentence of paragraph [0145]). Jacobsen et al specifically taught that various linkers may be used in the construction of recombinant proteins, and specifically stated “The XTEN linker, SGSETPGTSESATPES (SEQ ID NO: 166), and variants thereof, described in Guilinget et al, 2014 (Nature Biotechnology 32, 577-582), may also be used. This particular linker was previously shown to produce the best results among other linkers in a protein fusion between dCAS9 and the nuclease Fok1” (last two sentences of paragraph [0141]). The XTEN linker with the sequence SGSETPGTSESATPES is 100% identical to SEQ ID NO: 5 of the present application. Jacobsen et al further disclosed that suitable TET1 proteins include those listed in Table 1 such as the human TET1 protein of SEQ ID NO: 1 that is 100% identical to SEQ ID NO: 1 of the present application (paragraph [0185]), Table 1; and attached sequence search below).
Although the reference did not explicitly disclosed a fusion protein comprising from N-terminus to C-terminus TET1-XTEN linker-dCas9, TET1-XTEN linker-Zinc finger domain, or TET1-XTEN linker-TALE; however, since Jacobsen et al taught that various linkers can be used in the construction of recombinant proteins, particularly the XTEN linker with the sequence of SGSETPGTSESATPES, and specifically that an exemplary TET1-CAS9 fusion is an indirect fusion protein; it would have been obvious for an ordinary skill in the art to also prepare a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker, and a nuclease-deficient RNA-guided DNA endonuclease (e.g., dCas9) or a nuclease-deficient DNA endonuclease enzyme (e.g., a zinc finger nuclease or a TALE), wherein the demethylation is a TET1 domain based on the disclosure of Jacobsen et al.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Jacobsen et al (US 2019/0352654; IDS) as applied to claims 1, 4, 7, 22, 49, 51 and 60 above, and further in view of Cheng et al (US 11,780,895).
The teachings of Jacobsen et al were presented above. However, Jacobsen et al did not teach specifically a fusion protein comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 112 (2132-amino-acid sequence) of the present application.
Before the effective filing date of the present application (06/05/2020), Cheng et al also taught a demethylation domain (e.g., TET1 domain) may be linked to a nuclease-deficient RNA-guided DNA endonuclease (e.g., dCas9) directly or via a chemical linker which is a peptide linker (e.g., a poly-glycine linker); and in certain embodiments, the demethylation domain is linked to the N-terminus of the nuclease-deficient RNA-guided DNA endonuclease; including the dCas9-demethylation domain (e.g., TET1 domain) conjugate having SEQ ID NO: 52 that is 98% sequence identity to SEQ ID NO: 112 of the present application (Abstract; and particularly col. 27, lines 8-37; SEQ ID NO: 52; and attached sequence search below). It is also noted that SEQ ID NO: 52 of Cheng et al is a fusion protein comprising from the N-terminus to C-terminus a TET1 domain-a poly-glycine linker-dCas9.
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the teachings of Jacobsen et al by also utilizing at least the fusion protein TET1-XTEN-dCas9 having at least 98% identical to SEQ ID NO: 112 of the present application, in light of the teachings of Cheng et al as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modification because Cheng et al already disclosed using the conjugate of SEQ ID NO: 52 comprised of a TET1 domain-a poly-glycine linker-dCas9, that is already 98% identical to SEQ ID NO: 112 of the present application for a method of demethylation a target DNA sequence in a mammalian cell, let alone the primary Jacobsen already taught a fusion protein of the format TET1-XTEN-dCas9 for inducing a targeted gene demethylation.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Jacobsen et al and Cheng et al; coupled with a high level of skill of an ordinary skilled artisan in the relevant art.
The modified fusion protein resulting from the combined teachings of Jacobsen et al and Cheng et al as set forth above is indistinguishable from and encompassed by the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., whose telephone number is (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631
Sequence 1, US/16480623A
ORGANISM: Homo sapiens
Query Match 100.0%; Score 11210; Length 2136;
Best Local Similarity 100.0%;
Matches 2136; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSRSRHARPSRLVRKEDVNKKKKNSQLRKTTKGANKNVASVKTLSPGKLKQLIQERDVKK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSRSRHARPSRLVRKEDVNKKKKNSQLRKTTKGANKNVASVKTLSPGKLKQLIQERDVKK 60
Qy 61 KTEPKPPVPVRSLLTRAGAARMNLDRTEVLFQNPESLTCNGFTMALRSTSLSRRLSQPPL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KTEPKPPVPVRSLLTRAGAARMNLDRTEVLFQNPESLTCNGFTMALRSTSLSRRLSQPPL 120
Qy 121 VVAKSKKVPLSKGLEKQHDCDYKILPALGVKHSENDSVPMQDTQVLPDIETLIGVQNPSL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VVAKSKKVPLSKGLEKQHDCDYKILPALGVKHSENDSVPMQDTQVLPDIETLIGVQNPSL 180
Qy 181 LKGKSQETTQFWSQRVEDSKINIPTHSGPAAEILPGPLEGTRCGEGLFSEETLNDTSGSP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LKGKSQETTQFWSQRVEDSKINIPTHSGPAAEILPGPLEGTRCGEGLFSEETLNDTSGSP 240
Qy 241 KMFAQDTVCAPFPQRATPKVTSQGNPSIQLEELGSRVESLKLSDSYLDPIKSEHDCYPTS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 KMFAQDTVCAPFPQRATPKVTSQGNPSIQLEELGSRVESLKLSDSYLDPIKSEHDCYPTS 300
Qy 301 SLNKVIPDLNLRNCLALGGSTSPTSVIKFLLAGSKQATLGAKPDHQEAFEATANQQEVSD 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SLNKVIPDLNLRNCLALGGSTSPTSVIKFLLAGSKQATLGAKPDHQEAFEATANQQEVSD 360
Qy 361 TTSFLGQAFGAIPHQWELPGADPVHGEALGETPDLPEIPGAIPVQGEVFGTILDQQETLG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TTSFLGQAFGAIPHQWELPGADPVHGEALGETPDLPEIPGAIPVQGEVFGTILDQQETLG 420
Qy 421 MSGSVVPDLPVFLPVPPNPIATFNAPSKWPEPQSTVSYGLAVQGAIQILPLGSGHTPQSS 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 MSGSVVPDLPVFLPVPPNPIATFNAPSKWPEPQSTVSYGLAVQGAIQILPLGSGHTPQSS 480
Qy 481 SNSEKNSLPPVMAISNVENEKQVHISFLPANTQGFPLAPERGLFHASLGIAQLSQAGPSK 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 SNSEKNSLPPVMAISNVENEKQVHISFLPANTQGFPLAPERGLFHASLGIAQLSQAGPSK 540
Qy 541 SDRGSSQVSVTSTVHVVNTTVVTMPVPMVSTSSSSYTTLLPTLEKKKRKRCGVCEPCQQK 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SDRGSSQVSVTSTVHVVNTTVVTMPVPMVSTSSSSYTTLLPTLEKKKRKRCGVCEPCQQK 600
Qy 601 TNCGECTYCKNRKNSHQICKKRKCEELKKKPSVVVPLEVIKENKRPQREKKPKVLKADFD 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 TNCGECTYCKNRKNSHQICKKRKCEELKKKPSVVVPLEVIKENKRPQREKKPKVLKADFD 660
Qy 661 NKPVNGPKSESMDYSRCGHGEEQKLELNPHTVENVTKNEDSMTGIEVEKWTQNKKSQLTD 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 NKPVNGPKSESMDYSRCGHGEEQKLELNPHTVENVTKNEDSMTGIEVEKWTQNKKSQLTD 720
Qy 721 HVKGDFSANVPEAEKSKNSEVDKKRTKSPKLFVQTVRNGIKHVHCLPAETNVSFKKFNIE 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 HVKGDFSANVPEAEKSKNSEVDKKRTKSPKLFVQTVRNGIKHVHCLPAETNVSFKKFNIE 780
Qy 781 EFGKTLENNSYKFLKDTANHKNAMSSVATDMSCDHLKGRSNVLVFQQPGFNCSSIPHSSH 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 EFGKTLENNSYKFLKDTANHKNAMSSVATDMSCDHLKGRSNVLVFQQPGFNCSSIPHSSH 840
Qy 841 SIINHHASIHNEGDQPKTPENIPSKEPKDGSPVQPSLLSLMKDRRLTLEQVVAIEALTQL 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 SIINHHASIHNEGDQPKTPENIPSKEPKDGSPVQPSLLSLMKDRRLTLEQVVAIEALTQL 900
Qy 901 SEAPSENSSPSKSEKDEESEQRTASLLNSCKAILYTVRKDLQDPNLQGEPPKLNHCPSLE 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 SEAPSENSSPSKSEKDEESEQRTASLLNSCKAILYTVRKDLQDPNLQGEPPKLNHCPSLE 960
Qy 961 KQSSCNTVVFNGQTTTLSNSHINSATNQASTKSHEYSKVTNSLSLFIPKSNSSKIDTNKS 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 KQSSCNTVVFNGQTTTLSNSHINSATNQASTKSHEYSKVTNSLSLFIPKSNSSKIDTNKS 1020
Qy 1021 IAQGIITLDNCSNDLHQLPPRNNEVEYCNQLLDSSKKLDSDDLSCQDATHTQIEEDVATQ 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 IAQGIITLDNCSNDLHQLPPRNNEVEYCNQLLDSSKKLDSDDLSCQDATHTQIEEDVATQ 1080
Qy 1081 LTQLASIIKINYIKPEDKKVESTPTSLVTCNVQQKYNQEKGTIQQKPPSSVHNNHGSSLT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 LTQLASIIKINYIKPEDKKVESTPTSLVTCNVQQKYNQEKGTIQQKPPSSVHNNHGSSLT 1140
Qy 1141 KQKNPTQKKTKSTPSRDRRKKKPTVVSYQENDRQKWEKLSYMYGTICDIWIASKFQNFGQ 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 KQKNPTQKKTKSTPSRDRRKKKPTVVSYQENDRQKWEKLSYMYGTICDIWIASKFQNFGQ 1200
Qy 1201 FCPHDFPTVFGKISSSTKIWKPLAQTRSIMQPKTVFPPLTQIKLQRYPESAEEKVKVEPL 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 FCPHDFPTVFGKISSSTKIWKPLAQTRSIMQPKTVFPPLTQIKLQRYPESAEEKVKVEPL 1260
Qy 1261 DSLSLFHLKTESNGKAFTDKAYNSQVQLTVNANQKAHPLTQPSSPPNQCANVMAGDDQIR 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 DSLSLFHLKTESNGKAFTDKAYNSQVQLTVNANQKAHPLTQPSSPPNQCANVMAGDDQIR 1320
Qy 1321 FQQVVKEQLMHQRLPTLPGISHETPLPESALTLRNVNVVCSGGITVVSTKSEEEVCSSSF 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 FQQVVKEQLMHQRLPTLPGISHETPLPESALTLRNVNVVCSGGITVVSTKSEEEVCSSSF 1380
Qy 1381 GTSEFSTVDSAQKNFNDYAMNFFTNPTKNLVSITKDSELPTCSCLDRVIQKDKGPYYTHL 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 GTSEFSTVDSAQKNFNDYAMNFFTNPTKNLVSITKDSELPTCSCLDRVIQKDKGPYYTHL 1440
Qy 1441 GAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLC 1500
Qy 1501 LVRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYNGHPTDRRCTLNENRT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 LVRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYNGHPTDRRCTLNENRT 1560
Qy 1561 CTCQGIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 CTCQGIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLA 1620
Qy 1621 TRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGVTACLDFCAHPHRDIHNMNN 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGVTACLDFCAHPHRDIHNMNN 1680
Qy 1681 GSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPR 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 GSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPR 1740
Qy 1741 RKKRTCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPIPRIKRKNNSTTTNNSKPSSLPT 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 RKKRTCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPIPRIKRKNNSTTTNNSKPSSLPT 1800
Qy 1801 LGSNTETVQPEVKSETEPHFILKSSDNTKTYSLMPSAPHPVKEASPGFSWSPKTASATPA 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 LGSNTETVQPEVKSETEPHFILKSSDNTKTYSLMPSAPHPVKEASPGFSWSPKTASATPA 1860
Qy 1861 PLKNDATASCGFSERSSTPHCTMPSGRLSGANAAAADGPGISQLGEVAPLPTLSAPVMEP 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 PLKNDATASCGFSERSSTPHCTMPSGRLSGANAAAADGPGISQLGEVAPLPTLSAPVMEP 1920
Qy 1921 LINSEPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPMEEDEQHSEADEPPSDEPLSDDPL 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 LINSEPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPMEEDEQHSEADEPPSDEPLSDDPL 1980
Qy 1981 SPAEEKLPHIDEYWSDSEHIFLDANIGGVAIA PAHGSVLIECARRELHATTPVEHPNRNH 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 SPAEEKLPHIDEYWSDSEHIFLDANIGGVAIA PAHGSVLIECARRELHATTPVEHPNRNH 2040
Qy 2041 PTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKMKASEQKDQAANEGPEQSSEVNE 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 PTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKMKASEQKDQAANEGPEQSSEVNE 2100
Qy 2101 LNQIPSHKALTLTHDNVVTVSPYALTHVAGPYNHWV 2136
||||||||||||||||||||||||||||||||||||
Db 2101 LNQIPSHKALTLTHDNVVTVSPYALTHVAGPYNHWV 2136
Sequence 52, US/16333134
Patent No. 11780895
Query Match 98.0%; Score 10847.5; Length 2157;
Best Local Similarity 98.3%;
Matches 2099; Conservative 2; Mismatches 10; Indels 25; Gaps 3;
Qy 3 LPTCSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKS 62
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 6 LPTCSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKS 65
Qy 63 SHGCPIAKWVLRRSSDEEKVLCLVRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELT 122
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 66 SHGCPIAKWVLRRSSDEEKVLCLVRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELT 125
Qy 123 ENLKSYNGHPTDRRCTLNENRTCTCQGIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRR 182
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 126 ENLKSYNGHPTDRRCTLNENRTCTCQGIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRR 185
Qy 183 FRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPF 242
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 186 FRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPF 245
Qy 243 SGVTACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDE 302
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 246 SGVTACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDE 305
Qy 303 FGSKEGMEAKIKSGAIEVLAPRRKKRTCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPI 362
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 306 FGSKEGMEAKIKSGAIEVLAPRRKKRTCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPI 365
Qy 363 PRIKRKNNSTTTNNSKPSSLPTLGSNTETVQPEVKSETEPHFILKSSDNTKTYSLMPSAP 422
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 366 PRIKRKNNSTTTNNSKPSSLPTLGSNTETVQPEVKSETEPHFILKSSDNTKTYSLMPSAP 425
Qy 423 HPVKEASPGFSWSPKTASATPAPLKNDATASCGFSERSSTPHCTMPSGRLSGANAAAADG 482
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 426 HPVKEASPGFSWSPKTASATPAPLKNDATASCGFSERSSTPHCTMPSGRLSGANAAAADG 485
Qy 483 PGISQLGEVAPLPTLSAPVMEPLINSEPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPME 542
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 486 PGISQLGEVAPLPTLSAPVMEPLINSEPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPME 545
Qy 543 EDEQHSEADEPPSDEPLSDDPLSPAEEKLPHIDEYWSDSEHIFLDANIGGVAIA PAHGSV 602
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 546 EDEQHSEADEPPSDEPLSDDPLSPAEEKLPHIDEYWSDSEHIFLDANIGGVAIA PAHGSV 605
Qy 603 LIECARRELHATTPVEHPNRNHPTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKM 662
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 606 LIECARRELHATTPVEHPNRNHPTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKM 665
Qy 663 KASEQKDQAANEGPEQSSEVNELNQIPSHKALTLTHDNVVTVSPYALTHVAGPYNHWV-- 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 666 KASEQKDQAANEGPEQSSEVNELNQIPSHKALTLTHDNVVTVSPYALTHVAGPYNHWVID 725
Qy 721 ----SGSETPGTSESATP---------------ESMDKKYSIGLAIGTNSVGWAVITDEY 761
|| | | | |: ||||||||||||||||||||||||
Db 726 GGGGSGGGGSGGGGSMYPYDVPDYASPKKKRKVEASDKKYSIGLAIGTNSVGWAVITDEY 785
Qy 762 KVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEI 821
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 786 KVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEI 845
Qy 822 FSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDS 881
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 846 FSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDS 905
Qy 882 TDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASG 941
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 906 TDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASG 965
Qy 942 VDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQ 1001
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 966 VDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQ 1025
Qy 1002 LSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRY 1061
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1026 LSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRY 1085
Qy 1062 DEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDG 1121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1086 DEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDG 1145
Qy 1122 TEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILT 1181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1146 TEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILT 1205
Qy 1182 FRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNE 1241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1206 FRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNE 1265
Qy 1242 KVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLK 1301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1266 KVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLK 1325
Qy 1302 EDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTL 1361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1326 EDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTL 1385
Qy 1362 FEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKS 1421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1386 FEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKS 1445
Qy 1422 DGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVD 1481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1446 DGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVD 1505
Qy 1482 ELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQ 1541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1506 ELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQ 1565
Qy 1542 LQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRG 1601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1566 LQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRG 1625
Qy 1602 KSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETR 1661
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1626 KSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETR 1685
Qy 1662 QITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAH 1721
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1686 QITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAH 1745
Qy 1722 DAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNF 1781
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1746 DAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNF 1805
Qy 1782 FKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGF 1841
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1806 FKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGF 1865
Qy 1842 SKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLG 1901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1866 SKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLG 1925
Qy 1902 ITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE 1961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1926 ITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE 1985
Qy 1962 LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADA 2021
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1986 LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADA 2045
Qy 2022 NLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDA 2081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2046 NLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDA 2105
Qy 2082 TLIHQSITGLYETRIDLSQLGGDGGGGSPKKKRKVD 2117
||||||||||||||||||||||| ||||||||:
Db 2106 TLIHQSITGLYETRIDLSQLGGD----SPKKKRKVE 2137