COMPOSITIONS AND METHODS FOR EPIGENOME EDITING

§103 §112

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 . Applicant’s amendment filed on 07/23/2026 has been entered for the purpose of a compact prosecution even though the claim amendment filed on 07/23/2026 does not comply with the requirements of 37 CFR 1.121(c) because claim texts are still presented for cancelled claims 22 and 60. Amended claims 1, 4, 7, 10, 15, 18, 20, 24, 30, 33-34, 39, 41, 44, 49, 51, 58 and 68 are pending in the present application. Applicant elected previously without traverse the Invention of Group I, which is 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. Applicant also elected previously 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. It is noted that Applicant cancelled the elected species of SEQ ID NO: 5 for an XTEN linker and SEQ ID NO:112 for a fusion protein in the claim amendment filed on 07/23/2026. Accordingly, the Examiner proceeded to examine SEQ ID NO: 6 and SEQ ID NO:111 as the respective replacements of cancelled SEQ ID NO: 5 and SEQ ID NO: 112. In addition to the elected dCas9, the examiner also examined previously a nuclease-deficient DNA endonuclease enzyme which was inadvertently not restricted in the Restriction Requirement dated 7/17/2025. Claims 10, 15, 18, 20, 24, 33-34, 39, 41, 44, 58 and 68 were withdrawn previously from further considerations because they are directed to non-elected inventions. Accordingly, amended claims 1, 4, 7, 30, 49 and 51 are examined on the merits herein with the remaining elected species along with a nuclease-deficient DNA endonuclease enzyme. Response to Amendment 1. The rejection under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for Scope of Enablement was withdrawn in light of currently amended claim 49 and the cancellation of claims 22 and 60. 2. The rejection under 35 U.S.C. 102(a)(1) as being anticipated by Jacobsen et al (US 2019/0352654; IDS) was withdrawn in light of currently amended independent claims 1 and 49, particularly with the new limitation “wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues”. 3. The alternative rejection under 35 U.S.C. 103 as being unpatentable over Jacobsen et al (US 2019/0352654; IDS) was also withdrawn in light of currently amended independent claims 1 and 49, particularly with the new limitation “wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues”. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Amended claim 30 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Dependent claim 30 recites at least a fusion protein comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 111 or comprising SEQ ID NO: 111. However, the recited SEQ ID NO: 111 appears to be the amino acid sequence of the fusion protein comprising from N-terminus to C-terminus, dCas9, an XTEN linker and a TET domain; and NOT a fusion comprising from N-terminus to C-terminus, a TET domain, an XTEN linker and dCas9 as required by independent claim 1. This is evident by the homology search of SEQ ID NO: 111 that exhibits 98.8% sequence identity to the dCas9-TetCD of SEQ ID NO: 159 of Jaenisch et al (US 11,434,476) (see attached sequence search below). Additionally, it appears that the XTEN linker in SEQ ID NO: 111 also does not meet the limitation of “wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues” recited in independent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. This is a new ground of rejection necessitated by Applicant’s amendment. 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. Amended claims 1, 4, 7, 49 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Jacobsen et al (US 2019/0352654; IDS) in view of Cotta-Ramusino et al (WO2017/180694), Liu et al (US 12,060,586) and Schellenberger et al (US 8,673,860). This is a new ground of rejection necessitated by Applicant’s amendment. The instant claims are directed to a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker (e.g., SEQ ID NO: 6 or SEQ ID NO: 98), and a nuclease-deficient RNA-guided DNA endonuclease (e.g., the elected dCas9) or a nuclease-deficient DNA endonuclease enzyme is a zinc finger 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; wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues. 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; helix-turn-helix family DNA-binding domains; 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 “Linkers may be used in the TET1-CAS9 fusion proteins described herein to separate the coding sequences of a TET1 polypeptide and a CAS9 protein. For example, a variety of wiggly/flexible linkers, stiff/rigid linkers, short linkers, and long linkers may be used as described herein” (paragraph [0140]), and “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 that 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 or a TALE), wherein the demethylation is a TET1 domain. Jacobsen et al did not teach explicitly a fusion protein of TET1-XTEN linker-dCas9 or TET1-XTEN linker-Zinc finger domain, wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues. Before the effective filing date of the present application (06/05/2020), Cotta-Ramusino et al already disclosed a Cas9 fusion molecule comprising a Cas9 polypeptide linked to a template nucleic acid sequence using a polypeptide linker to increase the frequency and efficiency of DNA repair of DSBs using gene correction, wherein the polypeptide linker is between about 3 to about 100 amino acids in length and wherein the polypeptide linker includes an XTEN linker with the exemplary XTEN linker with the amino acid sequence SGSETPGTSESATPES (Summary; particularly last two paragraphs on page 3; lines 9-32 at page 33; lines 13-17 at page 34). Cotta-Ramusino et al also taught that the linker may be attached to the N-terminus of a Cas9 molecule (line 18 at page 33); and stated “In other embodiments, the polypeptide linker is sufficiently long to allow the eaCas9 bind to the a target nucleic acid without steric interference” (lines 24-26 at page 3). Additionally, Liu et al also disclosed a fusion protein comprising a nuclease-inactive Cas9 domain and a nucleic acid editing domain (e.g., a deaminase domain, a nuclease, a nickase, a recombinase, a methytransferase, a methylase, a transcriptional activator) that are linked via a linker (see at least col. 32, line 50 continues to line 24 at col. 33; and lines 14-51 at col. 34). Liu et al stated “A linker may be, for example, an amino acid sequence, a peptide, or a polymer of any length and composition” (col. 34, lines 18-20); “In some embodiments, the linker is 1-100 amino acids in length,….., or 150-200 amino acid in length. Longer or shorter linkers are also contemplated. In some embodiments, a linker comprises the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 306), which may also be referred as the XTEN linker” (lines 41-51 at col. 34). Moreover, Schellenberger et al also disclosed a biological active protein (BP) linked to extended recombinant polypeptide (XTEN), wherein XTEN are long polypeptides having greater than about 100 to about 3000 amino acid residues, wherein the XTEN may exhibit one or more of the following advantageous properties: conformation flexibility, enhanced aqueous solubility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors, and increased hydrodynamic radii, properties that can make them particularly useful s fusion protein partners (Abstract; particularly col. 24, line 40 continues to line 37 at col. 25). Schellenberger et al also stated clearly “In other cases, where an increase in half-life of the fusion protein is not needed but where an increase in solubility or other physio/chemical property of the biologically active protein fusion partner is desired, an XTEN sequence shorter than 100 amino acid residues, such as about 96, or about 84, or about 72, or about 60, or about 48, or about 36 amino acid residues may be incorporated into a fusion protein composition with the BP to effect the property” (col. 25, lines 3-10). Schellenberger et al disclosed the exemplary BPXTEN fusion protein Ex4-XTEN (extendin-4 linked to AE576 or Ex4-AE576) of SEQ ID NO: 1056 (616-amino-acid sequence) in which the sequence of amino acid residues 29-108 in SEQ ID NO: 1056 is 100% identical to SEQ ID NO: 6 of the present application (col. 13, lines 52-67; Fig. 22 and Table 40; attached sequence search below). 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 selecting at least an XTEN linker comprising from about 80 amino acid residues or more, including the XTEN linker comprising amino acid residues 29-108 of SEQ ID NO: 1056 disclosed in Schellenberger et al, as an XTEN linker for the fusion protein of TET1-XTEN linker-dCas9 or TET1-XTEN linker-Zinc finger domain, in light of the teachings of Cotta-Ramusino et al, Liu et al and Schellenberger et al as presented above. An ordinary skilled artisan would have been motivated to carry out the above modification because: (i) Cotta-Ramusino et al already disclosed the use of a polypeptide linker that is between about 3 to about 100 amino acids in length and wherein the polypeptide linker includes an XTEN linker in a Cas9 fusion molecule gene editing system; (ii) Liu et al also disclosed a fusion protein comprising a nuclease-inactive Cas9 domain and a nucleic acid editing domain that are linked via a linker of any length and composition, including the linker that is 1-100 amino acids in length, or 150-200 amino acid in length; and (iii) Schellenberger et al also disclosed a biological active protein (BP) linked to extended recombinant polypeptide (XTEN), wherein XTEN are long polypeptides having greater than about 100 to about 3000 amino acid residues, wherein the XTEN may exhibit one or more of the following advantageous properties: conformation flexibility, enhanced aqueous solubility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors, and increased hydrodynamic radii, properties that can make them particularly useful s fusion protein partners. Moreover, Schellenberger et al also taught that where an increase in solubility or other physio/chemical property of the biologically active protein fusion partner is desired, an XTEN sequence shorter than 100 amino acid residues, such as about 96, or about 84, may be incorporated into a fusion protein composition; along with the exemplary Ex4-AE576 fusion protein of SEQ ID NO: 1056 (616-amino-acid sequence) in which the sequence of amino acid residues 29-108 in SEQ ID NO: 1056 is 100% identical to SEQ ID NO: 6 of the present application. Thus, at least an XTEN linker comprising the sequence of amino acid residues 29-108 in SEQ ID NO: 1056 will confer fusion protein of TET1-XTEN linker-dCas9 or TET1-XTEN linker-Zinc finger domain a desired increase in solubility or other physio/chemical property, along with other advantageous properties (e.g., conformation flexibility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors) for XTEN linker that is about 100 amino acid residues or more. Furthermore, the primary Jacobsen reference already taught that short and long linkers can be used in their disclosed fusion proteins. An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Jacobsen et al, Cotta-Ramusino et al, Liu et al and Schellenberger 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, Cotta-Ramusino et al, Liu et al and Schellenberger 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. Amended claims 1, 4, 7, 49 and 51 are rejected under 35 U.S.C. 103 as being obvious over Jacobsen et al (US 2019/0352654; IDS) in view of Chen et al (WO 2019/204766 with an effective filing date of 04/19/2018). This is a new ground of rejection necessitated by Applicant’s amendment. The applied reference has a common Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). 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; helix-turn-helix family DNA-binding domains; 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 “Linkers may be used in the TET1-CAS9 fusion proteins described herein to separate the coding sequences of a TET1 polypeptide and a CAS9 protein. For example, a variety of wiggly/flexible linkers, stiff/rigid linkers, short linkers, and long linkers may be used as described herein” (paragraph [0140]), and “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 that 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 or a TALE), wherein the demethylation is a TET1 domain. Jacobsen et al did not teach explicitly a fusion protein of TET1-XTEN linker-dCas9 or TET1-XTEN linker-Zinc finger domain, wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues. Before the effective filing date of the present application (06/05/2020), Chen et al already disclosed at least a fusion protein comprises, from N-terminus to C-terminus, a DNA methyltransferase domain, a nuclease-deficient RNA-guided DANA endonuclease enzyme, and KRAB domain, wherein the fusion protein further comprises one or more peptide linkers, wherein the one or more peptide linkers include an XTEN linker such as XTEN80 linker with the amino acid sequence of SEQ ID NO: 32 that is 100% identical to SEQ ID NO: 6 of the present application (see at least Brief Summary, particularly paragraphs [0005], [0010], [0074], [0077], [0087]-[0088], [0092]; FIG. 5 and attached sequence search below). A part of Fig. 5 depicts some exemplary fusion proteins comprising the structure: C-L3-A-L4-B-L5-D including p112 as shown below, wherein C comprises a DNA methyltransferase domain, A comprises a nuclease-deficient RNA-guided DNA endonuclease enzyme, B comprises a KRAB domain, and D comprises a detectable tag. PNG media_image1.png 414 615 media_image1.png Greyscale 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 the XTEN80 linker for their disclosed fusion protein, in light of the teachings of Chen et al as presented above. An ordinary skilled artisan would have been motivated to carry out the above modification because Chen et al already taught successfully using at least the XTEN80 linker with the amino acid sequence of SEQ ID NO: 32 that is 100% identical to SEQ ID NO: 6 of the present application to form a functional fusion protein comprises, from N-terminus to C-terminus, a DNA methyltransferase domain, a nuclease-deficient RNA-guided DANA endonuclease enzyme, and KRAB domain. Moreover, please note that the primary Jacobsen reference already taught that short and long linkers can be used in their disclosed fusion proteins. An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Jacobsen et al and Chen 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 Chen 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. This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Response to Arguments Applicant’s arguments related to the above new 103 rejections in the Amendment filed on 07/23/2026 (pages 9-12) have been fully considered, but they are respectfully not found persuasive for the reasons discussed below. A. Applicant argued basically that Jacobsen fails to teach a fusion protein including an XTEN linker that includes between 80 amino acids and 864 amino acids, and Jacobsen teaches “short peptides” as linkers for use in a fusion protein with a single XTEN linker sequence that is 16 amino acids long. Applicant argued that an ordinary skilled artisan would understand that Jacobsen identifies XTEN16 as a preferred XTEN linker and provides no teaching or suggestion that substantially longer XTEN linkers would improve reactivation activity; and thus the selection of this specific XTEN linker range can only be reconstructed using the instant specification as a roadmap, which is a type of impermissible hindsight reasoning. Applicant also argued that even an ordinary skilled artisan were motivated to modify the linker length taught by Jacobsen, an ordinary skilled artisan modified Jacobsen’s fusion proteins to include a linker five to over fifty times longer would have had no reasonable expectation that the resulting fusion protein would even retain function, let alone achieve the substantial and durable increase in gene reactivation efficiency that Applicant have demonstrated. Applicant further argued that Jacobsen is silent on any beneficial effect of the specific N- to C-terminus order of the claimed fusion protein’s domains. Rather, Jacobsen consistently exemplifies fusion proteins including a demethylation domain (e.g., TET1-CD) and a nuclease-deficient RNA guided DNA endonuclease enzyme (e.g., dCas9) in the reverse order from that recited in the instant claims. In contrast, Applicants demonstrated that fusion proteins including the claimed N- to C- terminus order of a demethylation domain, an XTEN linker, and a nuclease deficient RNA-guided DNA endonuclease enzyme, exhibited increased efficacy in reactivating genes (e.g., TETv3 and TETv4) compared to TETv2 comprising from N- to C-terminus, a nuclease deficient RNA-guided DNA endonuclease, an XTEN linker, and a demethylation domain (paragraph [0264] and FIGS. 5-7). First, the instant claims are directed to a fusion protein comprising from N-terminus to C-terminus, a demethylation domain, an XTEN linker (e.g., SEQ ID NO: 6 or SEQ ID NO: 98), and a nuclease-deficient RNA-guided DNA endonuclease (e.g., the elected dCas9) or a nuclease-deficient DNA endonuclease enzyme is a zinc finger 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; wherein the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues. It is noted that there is no requirement whatsoever that the claimed fusion protein is functional, let alone any substantial and/or durable increase in reactivation efficiency as Applicant argued above. Second, please refer to the above new 103 rejections above for detail along with the motivations provided for combining the cited references. Additionally, please note since the above rejections were made under 35 U.S.C. 103, none of the cited references individually must teach every limitation of the instant claims. For example, the primary Jacobsen reference does not have to teach or suggest using an XTEN linker comprising from about 80 amino acid residues to about 864 amino acid residues. Third, 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, 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]); “Linkers may be used in the TET1-CAS9 fusion proteins described herein to separate the coding sequences of a TET1 polypeptide and a CAS9 protein. For example, a variety of wiggly/flexible linkers, stiff/rigid linkers, short linkers, and long linkers may be used as described herein” (paragraph [0140]), and “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]). Accordingly, based on these specific teachings an ordinary skill in the art would readily recognize that 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 or a TALE), wherein the demethylation is a TET1 domain, wherein the XTEN linker includes SEQ ID NO: 166 or variants thereof. It is irrelevant whether Jacobsen et al recognize any beneficial effect of the specific N- to C-terminus order of the claimed fusion protein’s domain because Jacobsen et al already taught such a fusion protein. Moreover, please note that the teachings of Jacobsen et al are not necessarily limited only to working examples. Fourth, with respect to Applicant’s argument on impermissible hindsight reconstruction Examiner would like to recite a paragraph from in re Oetiker, 977, F.2d 1443, 1448 (Fed. Cir. 1992). "[T]here must be some teaching, reason, suggestion, or motivation found "in the prior art" or "in the prior art references" to make a combination to render an invention obvious within the meaning of 35 U.S.C. 103 (1998). Similar language appears in a number of opinions and if taken literally would mean that an invention cannot be held to have been obvious unless something specific in a prior art reference would lead an inventor to combine the teachings therein with another piece of prior art. This restrictive understanding of the concept of obviousness is clearly wrong…. While there must be some teaching, reason, suggestion, or motivation to combine existing elements to produce the claimed device, it is not necessary that the cited references or prior art specifically suggest making the combination…. In sum, it is off the mark for litigants to argue, as many do, that an invention cannot be held to have been obvious unless a suggestion to combine the prior art teachings is found in a specific reference." Although the cited artisans do not specifically point out a motivation to in their disclosure, an ordinarily skilled artisan would have been able to identify the need for the combination of the teachings without the disclosure of the instant application. It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Please refer to the above modified 103 rejection for details along with the provided motivations for combining the cited references. Fifth, as set forth in the above 103 rejection based on Jacobsen et al, Cotta-Ramusino et al, Liu et al and Schellenberger et al, it would have been obvious for an ordinary skill in the art to modify the teachings of Jacobsen et al by also selecting at least an XTEN linker comprising from about 80 amino acid residues or more, including the XTEN linker comprising amino acid residues 29-108 of SEQ ID NO: 1056 disclosed in Schellenberger et al, as an XTEN linker for the fusion protein of TET1-XTEN linker-dCas9 or TET1-XTEN linker-Zinc finger domain because : (i) Cotta-Ramusino et al already disclosed the use of a polypeptide linker that is between about 3 to about 100 amino acids in length and wherein the polypeptide linker includes an XTEN linker in a Cas9 fusion molecule gene editing system; (ii) Liu et al also disclosed a fusion protein comprising a nuclease-inactive Cas9 domain and a nucleic acid editing domain that are linked via a linker of any length and composition, including the linker that is 1-100 amino acids in length, or 150-200 amino acid in length; and (iii) Schellenberger et al also disclosed a biological active protein (BP) linked to extended recombinant polypeptide (XTEN), wherein XTEN are long polypeptides having greater than about 100 to about 3000 amino acid residues, wherein the XTEN may exhibit one or more of the following advantageous properties: conformation flexibility, enhanced aqueous solubility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors, and increased hydrodynamic radii, properties that can make them particularly useful s fusion protein partners. Moreover, Schellenberger et al also taught that where an increase in solubility or other physio/chemical property of the biologically active protein fusion partner is desired, an XTEN sequence shorter than 100 amino acid residues, such as about 96, or about 84, may be incorporated into a fusion protein composition; along with the exemplary Ex4-AE576 fusion protein of SEQ ID NO: 1056 (616-amino-acid sequence) in which the sequence of amino acid residues 29-108 in SEQ ID NO: 1056 is 100% identical to SEQ ID NO: 6 of the present application. Thus, at least an XTEN linker comprising the sequence of amino acid residues 29-108 in SEQ ID NO: 1056 will confer fusion protein of TET1-XTEN linker-dCas9 or TET1-XTEN linker-Zinc finger domain a desired increase in solubility or other physio/chemical property, along with other advantageous properties (e.g., conformation flexibility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors) for XTEN linker that is about 100 amino acid residues or more. Furthermore, the primary Jacobsen reference already taught that short and long linkers can be used in their disclosed fusion proteins. Sixth, an ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Jacobsen et al, Cotta-Ramusino et al, Liu et al and Schellenberger et al; coupled with a high level of skill of an ordinary skilled artisan in the relevant art. Once again, please note that there is no requirement whatsoever that the claimed fusion protein is functional, let alone any substantial and/or durable increase in reactivation efficiency as Applicant argued above. Moreover, the standard under 35 U.S.C. is a “reasonable’ expectation of success. B. Applicant argued that it was surprising to find that increasing the length of the XTEN linker increased the efficiency of the claimed fusion proteins to activate and/or reactivate target nucleic acids. For example, over 70% of cells transfected with a fusion protein comprising an 80 amino acid XTEN linker (i.e. TETv4) had a reactivated target nucleic acid (e.g., CTLA), while only about 50% of cells transfected with a fusion protein comprising a 16 amino acid XTEN (i.e., TETv3) showed reactivation of CTLA (paragraph [0264]). Applicant also argued that the specification teaches examples of fusion proteins including an XTEN linker with 100 amino acid residues (i.e., XTEN100) and demonstrated that fusion protein including an XTEN100 linker successfully reactivated CLTA, DYNC2LI1, and H2B genes at 13 days post transfection (FIG. 19A-C). Applicant argued that the skilled artisan could not reasonably predict that modifying the teachings of Jacobsen to substitute a longer XTEN linker would result in a functional fusion protein, let alone a fusion protein with superior qualities as demonstrated by the present application. First, FIG. 5 of the present application that depicts the structures of TETv4 and TETv3 is reproduced below. PNG media_image2.png 218 533 media_image2.png Greyscale Second, apart from the single alleged “surprising” showing that over 70% of cells transfected with a fusion protein comprising an 80 amino acid XTEN linker (i.e. TETv4) had a reactivated target nucleic acid (e.g., CTLA), while only about 50% of cells transfected with a fusion protein comprising a 16 amino acid XTEN (i.e., TETv3) showed reactivation of CTLA (paragraph [0264]), there is no evidence of record indicating or suggesting that increasing the length of XTEN linker increased the efficiency of the claimed fusions protein to activate and/or reactivate target nucleic acids. For example, there is no evidence of record indicating that XTEN200 is more effective than XTEN150 which is more effective than XTEN100 which is more effective than XTEN80. On the contrary, the specification demonstrated clearly that XTEN100 linker is less effective in reactivating CTLA gene (with 80% cells off or only 20% reactivated, see FIG. 19B for TETv5) compared to XTEN80 linker (with about 70% cells reactivated; see FIG.6 for TETv4) and even XTEN16 (with about 50% of cells reactivated; see FIG. 6 for TETv3). Third, please note that any surprising result should be commensurate with the scope of the claims. The instant claims encompass a fusion protein comprising any nuclease-deficient RNA-guided DNA endonuclease enzyme that includes dCas9, a helix-turn-helix motif, a helix-loop-helix domain, an HMB-box domain, a Wor3 domain, an OB-fold domain, an immunoglobulin domain, a B3 domain (see dependent claim 4) and any XTEN linker sequence as long as the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues, or a fusion protein comprising any nuclease-deficient DNA endonuclease enzyme that is a zinc finger or a transcription activator-like effector (TALE) and any XTEN linker sequence as long as the XTEN linker comprises from about 80 amino acid residues to about 864 amino acid residues. It is noted that TETv4 comprises dCas9, the XTEN80 linker consisting of the sequence of SEQ ID NO: 6 and the TET1 DNA demethylase catalytic domain (paragraphs [0264] and [0303]). Third, once again there is no requirement whatsoever that the claimed fusion protein is functional, let alone any substantial and/or durable increase in reactivation efficiency as Applicant argued above. Moreover, the standard under 35 U.S.C. is a “reasonable’ expectation of success. Conclusion No claim is allowed. 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 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. Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll-free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. 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It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. /QUANG NGUYEN/Primary Examiner, Art Unit 1631 Sequence 159, US/16326700 Patent No. 11434476 dCAS9-Tet1CD Query Match 98.8%; Score 10938.5; Length 2115; Best Local Similarity 99.1%; Matches 2112; Conservative 0; Mismatches 3; Indels 17; Gaps 2; Qy 1 MDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAE 60 Qy 61 ATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFG 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 ATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFG 120 Qy 121 NIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSD 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 NIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSD 180 Qy 181 VDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGN 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 VDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGN 240 Qy 241 LIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAI 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 LIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAI 300 Qy 301 LLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 LLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYA 360 Qy 361 GYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELH 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 GYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELH 420 Qy 421 AILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEE 480 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 421 AILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEE 480 Qy 481 VVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFL 540 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 481 VVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFL 540 Qy 541 SGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKI 600 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 541 SGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKI 600 Qy 601 IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWG 660 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 601 IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWG 660 Qy 661 RLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSL 720 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 661 RLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSL 720 Qy 721 HEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRER 780 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 721 HEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRER 780 Qy 781 MKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDA 840 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 781 MKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDA 840 Qy 841 IVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL 900 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 841 IVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL 900 Qy 901 TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS 960 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 901 TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS 960 Qy 961 KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK 1020 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 961 KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK 1020 Qy 1021 MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDF 1080 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1021 MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDF 1080 Qy 1081 ATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVA 1140 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1081 ATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVA 1140 Qy 1141 YSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPK 1200 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1141 YSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPK 1200 Qy 1201 YSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVE 1260 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1201 YSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVE 1260 Qy 1261 QHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGA 1320 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1261 QHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGA 1320 Qy 1321 PAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDGGGGSPKKKRKV 1380 |||||||||||||||||||||||||||||||||||||||||||||||| | ||||||| Db 1321 PAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD-EGADPKKKRKV 1379 Qy 1381 DPKKKRKVDPKKKRKVGSGSETPGTSESATPESSLPTCSCLDRVIQKDKGPYYTHLGAGP 1440 ||||||||||||||||| ||||||||||||||||||||||||||| Db 1380 DPKKKRKVDPKKKRKVG----------------SLPTCSCLDRVIQKDKGPYYTHLGAGP 1423 Qy 1441 SVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLCLVRQ 1500 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1424 SVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLCLVRQ 1483 Qy 1501 RTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYNGHPTDRRCTLNENRTCTCQ 1560 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1484 RTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYNGHPTDRRCTLNENRTCTCQ 1543 Qy 1561 GIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLA 1620 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1544 GIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLA 1603 Qy 1621 PIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGVTACLDFCAHPHRDIHNMNNGSTV 1680 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1604 PIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGVTACLDFCAHPHRDIHNMNNGSTV 1663 Qy 1681 VCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPRRKKR 1740 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1664 VCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPRRKKR 1723 Qy 1741 TCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPIPRIKRKNNSTTTNNSKPSSLPTLGSN 1800 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1724 TCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPIPRIKRKNNSTTTNNSKPSSLPTLGSN 1783 Qy 1801 TETVQPEVKSETEPHFILKSSDNTKTYSLMPSAPHPVKEASPGFSWSPKTASATPAPLKN 1860 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1784 TETVQPEVKSETEPHFILKSSDNTKTYSLMPSAPHPVKEASPGFSWSPKTASATPAPLKN 1843 Qy 1861 DATASCGFSERSSTPHCTMPSGRLSGANAAAADGPGISQLGEVAPLPTLSAPVMEPLINS 1920 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1844 DATASCGFSERSSTPHCTMPSGRLSGANAAAADGPGISQLGEVAPLPTLSAPVMEPLINS 1903 Qy 1921 EPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPMEEDEQHSEADEPPSDEPLSDDPLSPAE 1980 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1904 EPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPMEEDEQHSEADEPPSDEPLSDDPLSPAE 1963 Qy 1981 EKLPHIDEYWSDSEHIFLDANIGGVAIA PAHGSVLIECARRELHATTPVEHPNRNHPTRL 2040 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1964 EKLPHIDEYWSDSEHIFLDANIGGVAIA PAHGSVLIECARRELHATTPVEHPNRNHPTRL 2023 Qy 2041 SLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKMKASEQKDQAANEGPEQSSEVNELNQI 2100 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2024 SLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKMKASEQKDQAANEGPEQSSEVNELNQI 2083 Qy 2101 PSHKALTLTHDNVVTVSPYALTHVAGPYNHWV 2132 |||||||||||||||||||||||||||||||| Db 2084 PSHKALTLTHDNVVTVSPYALTHVAGPYNHWV 2115 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 Fusion protein preparation related XTEN linker, SEQ 32. WO2019204766-A1. Query Match 100.0%; Score 419; Length 80; Best Local Similarity 100.0%; Matches 80; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 GGPSSGAPPPSGGSPAGSPTSTEEGTSESATPESGPGTSTEPSEGSAPGSPAGSPTSTEE 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 GGPSSGAPPPSGGSPAGSPTSTEEGTSESATPESGPGTSTEPSEGSAPGSPAGSPTSTEE 60 Qy 61 GTSTEPSEGSAPGTSTEPSE 80 |||||||||||||||||||| Db 61 GTSTEPSEGSAPGTSTEPSE 80 Sequence 1056, Patent No. 8673860 Query Match 100.0%; Score 419; Length 616; Best Local Similarity 100.0%; Matches 80; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 GGPSSGAPPPSGGSPAGSPTSTEEGTSESATPESGPGTSTEPSEGSAPGSPAGSPTSTEE 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 29 GGPSSGAPPPSGGSPAGSPTSTEEGTSESATPESGPGTSTEPSEGSAPGSPAGSPTSTEE 88 Qy 61 GTSTEPSEGSAPGTSTEPSE 80 |||||||||||||||||||| Db 89 GTSTEPSEGSAPGTSTEPSE 108