NZ715825B2 - Combination therapy for treatment of acromegaly - Google Patents

Abstract

The present disclosure relates to a method for treatment or prevention of acromegaly in a subject having an increased level of insulin-like growth factor I (IGF-I) despite Somatostatin agonist therapy. The method comprises administration of a Somatostatin analogs having agonistic activity, such as Octreotide, Lanreotide, Pasireotide, or Octreolin, in combination with an oligonucleotide targeted to growth hormone receptor (GHR) to a subject in need. In particular, the oligonucleotide targeted to GHR is ATL1103 defined by SEQ ID NO: 6 (tcagggcattctttccattc). ctreotide, Lanreotide, Pasireotide, or Octreolin, in combination with an oligonucleotide targeted to growth hormone receptor (GHR) to a subject in need. In particular, the oligonucleotide targeted to GHR is ATL1103 defined by SEQ ID NO: 6 (tcagggcattctttccattc).

Description

(12) Granted patent specificaon (19) NZ (11) 715825 (13) B2 (47) Publicaon date: 2021.12.24 (54) COMBINATION THERAPY FOR TREATMENT OF ACROMEGALY (51) Internaonal Patent Classificaon(s): A61K 31/7088A61K 38/31 A61P 31/00 A61P 5/02 (22) Filing date: (73) Owner(s): 2014.06.13 ANTISENSE THERAPEUTICS LTD (23) Complete specificaon filing date: (74) Contact: 2014.06.13 FB Rice Pty Ltd (30) aonal ty Data: (72) Inventor(s): US ,856 2013.06.13 TACHAS, George (86) Internaonal Applicaon No.: (87) Internaonal Publicaon : WO/2014/197938 (57) Abstract: The present disclosure relates to a method for treatment or prevenon of acromegaly in a subject having an increased level of insulin-like growth factor I (IGF-I) despite Somatostan agonist therapy. The method ses administraon of a Somatostan analogs having agonisc acvity, such as Octreode, Lanreode, Pasireode, or Octreolin, in combinaon with an oligonucleode targeted to growth e receptor (GHR) to a subject in need. In parcular, the oligonucleode targeted to GHR is ATL1103 defined by SEQ ID NO: 6 (tcagggcactccac).

NZ 715825 B2 "COMBINATION THERAPY FOR ENT OF ACROMEGALY" RELATED APPLICATION DATA This application claims ty from United States Patent ation No. 61/834,856 entitled “Combination therapy” filed on 13 June 2013. The entire contents of the application are hereby incorporated by reference.

SEQUENCE G A Sequence Listing is provided herewith as a text file, 513110_ST25.txt created on June 13, 2013 and having a size of 423 KB. The contents of the text file are incorporated by reference herein in their entirety.

FIELD The present disclosure relates to a method for treatment or prevention of diseases caused by and/or associated with an increased level of insulin-like growth factor I (IGF-I) that relies on administration of a Somatostatin analog having Somatostatin or agonistic activity in combination with an antisense oligonucleotide targeted to the growth hormone receptor (GHR).

BACKGROUND Growth hormone (GH), released by the pituitary, is a member of a cascade of hormones that regulate growth of the body and its organs. ion of GH into the bloodstream is followed by binding to growth hormone receptor (GHR) on many cell and organ types. Growth e signaling is mediated by this interaction. Growth hormone signaling causes the production of another hormone, insulin-like growth factor I (IGF-I), which is ed in the liver, adipose tissue, kidney and other organs and secreted into the bloodstream. About 75% of serum IGF-I is produced in the liver in response to GH stimulation. Many disorders are caused by and/or associated with increased GH levels and/or increased IGF-I levels in plasma and/or tissues including acromegaly, gigantism, retinopathy, macular ration, nephropathy, diabetes and s. The role of GH and IGF-I in these and other disorders is well recognized. The role of IGF-I in mediating many GH effects is well recognized and this interrelationship is referred to as the GH/IGF-I axis. In a normal feedback loop, IGF-I also causes the production of GH by the ary to be reduced. There is a need for treatments that reduce IGF-I levels in a subject, for example, more effectively, safely, conveniently and/or at reduced cost.

Somatostatin analogs having somatostatin receptor agonistic ty are approved in the treatment of acromegaly to reduce GH and serum IGF-I levels in a patient. For a review of current practices for the treatment of acromegaly see Guistina et al., 2011. Briefly, in galy, surgery is first used in ent to debulk the tumor and reduce the pituitary tumor’s GH ion and reduce production of IGF-I in the serum. nal treatments are also used to reduce serum IGF-I and in some cases also reduce GH e. All treatments use a medicinal monotherapy or a combination therapy directed to different biological protein s. First line medicinal ent is with a Somatostatin agonist, and this treatment is started initially at low doses and escalated to doses that reduce GH and normalize the patients serum IGF-I. When a Somatostatin agonist treatment fails, a dopamine agonist can be used in combination with a Somatostatin agonist, or Somavert is used in combination with a Somatostatin agonist or rt is used as a monotherapy. In patients where first line therapy using SST has failed or in patients where Somavert monotherapy or combination with Somatostatin has failed, clinicians are seeking new more effective treatments.

SUMMARY The t inventors have now made the surprising finding that a statin analog having Somatostatin receptor agonistic activity and an antisense oligonucleotide targeted to GHR act to produce additional activity to reduce insulin-like growth factor I (IGF-I) compared to Somatostatin receptor agonistic activity and/or act synergistically to reduce insulin-like growth factor I (IGF-I) levels in a subject. In other words, the combined administration of the Somatostatin agonist and the oligonucleotide to GHR exhibits enhanced therapeutic activity compared to the Somatostatin agonist, This is surprising, particularly considering that there are no expected synergies with using nse drugs targeted to the GHr, and a Somatostatin agonist.

Accordingly, the present disclosure provides a method for treatment or prevention of a disease caused by and/or associated with IGF—I, the method comprising administering to a subject in need thereof, a Somatostatin t in combination with an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid encoding GHR so as to inhibit expression of the GHR, thereby reducing the level of IGF-I in the subject. In one embodiment, the level of serum/plasma IGF-I is reduced. In one ment, the disease is caused by and/or ated with an increased level of IGF- In one embodiment, the method thither comprises identifying a suhieet in need of a reduction in said subject‘s GHR and/or {GP—I , for example serum/plasma IGF—I levels.

In one embodiment, the disease is aeromegaiy, ism, diabetic retinopathy, diabetic nephropathy, or an 'lGF—l positive and/or IGF-I andfor GH responsive cancer such as prostate, myeloma, iung, breast, or colon cancer.

In one embodiment, the Somatostaiin agonist has a higher binding affinity for human statin sub-type receptor 1 than the other human Somatostatin sub-type receptors, for human Somatostatin Sub-type receptor ‘2 than the other human if.) Somatostatin sub-type receptors, for human Somatostatin sub-type receptor 3 than the other human Somatostatin sub—type receptors, for human Somatostatin sub-type receptor 4 than the other human Somatostatin sub-type receptors, or for. human Somatostatin sub—type receptor 5 than the other human Somatostatih sub—type receptors; or wherein the Somatosratin t has a higher g affinity for two or more ofhuman Somarostatin receptor sub—types, for example, 1, 2, 3, 4 anchor 5.

In one embodiment, the statin agonist is for example ()etreotide, Lanreotide, or otide in short, medium or, longaeting fbrms or Octreohn. in a further embodiment, the Somatostarin agonist is a long acting release (LAR) form, for example, Octreotide-LAR (Sandestatinm‘i-LAR), Lanreotide—LAR (Lanreotide Autogel), or .Pasireotide-IAR, or is Lam‘eotide microparticles.

In one embodiment, the Somatostatin agonist. is: A3—f}T1p*L§-’S*A6"‘A ‘—A3‘-'R3r; " a >‘ or a pharmaceutically acceptable salt thereof, wherein A1 is a Di or I...~iso,mer ofAla, Leu, He, Val, Nle, Thr, Ser, [5»Nal, B—Pai, Trp, Phe, 2,4-diehloro-1Phe, penrafiuoro-Phe, p—X-Phe, or he; A3 is Ala, Leu, lle, Val, Nle, Phe, B—Nal, pyridyl—Ala, ’l7rp, chioro—Phe, uoro-Phe, e, or p-X-Phe; A3 is pyridyl~Ala, Trp, ,Phe, [fr-Nal, 2,4»diehloro~Phe, pentafluoro—Phe, o~X-Phe, or p—X-Phe; A6 is Val, Aia, Lou, He, Nle, Thr, Abe, or Ser; A7 is Ala, Lou, Ile, Val, Nle, Phe, B-Nal, pyridyl-Ala, Trp, 2,4«diohioro-Phe, pentafl'uoro—Phe, o-X-Phe, or p-X—Phe; 2014/000613 A8 is a D- or L-isomer of Ala, Leu, Ile, Val, Nle, Thr, Ser, Phe, B-Nal, pyridyl- Ala, Trp, 2,4—dichloro-Phe, pentafluoro-Phe, p-X-Phe, or o—X-Phe; wherein X for each occurrence is independently selected from the group consisting of CH3, Cl, Br, F, OH, OCH3 and N02; each R1 and R2, independently, is H, lower acyl or lower alkyl, and R3 is OH or NHz; provided that at least one of Al and A8 and one of A2 and A7 must be an aromatic amino acid, and further provided that Al, A2, A7 and A8 cannot all be aromatic amino acids.

In another embodiment, the Somatostatin agonist is: H-D-Phe-p—chloro-Phe-Tyr-D—Trp-Lys-Thr-Phe-Thr—lNHz; H-D-Phe-p-N02-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr-NH2, H-D-Nal-p-chloro-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr—1\H2; H-D-Phe-Phe—Phe-D-Trp-Lys-Thr-Phe-Thr-NH2, H-D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr—NH2; e-p-chloro-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr-NH2, or H-D-Phe-Ala-Tyr-D-Trp-Lys-Val-Ala-B-D-Nal-NHz; or a pharmaceutically acceptable salt thereof.

In another embodiment, the statin t is: D-Phe—Cys-Phe-D-Trp-Lys-Thr-Cys-B-Nal-NHz, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-B-Nal-NHZ; D-B-Nal-Cys-Phe-D-Trp-Lys—Thr—Cys-Thr-NHz, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NHZ; D-Phe-Cys-Phe-D-Trp-Lys-Thr-Pen-Thr-NHz, D-Phe—Cys-Tyr—D-Trp—Lys-Thr—Pen-Thr-OH; D-Phe-Cys-Phe-D-Trp-Lys-Thr-Pen—Thr-OH; Gly-Pen—Phe-D—Trp-Lys-Thr—Cys-Thr—OH; Phe-Pen-Tyr-D-Trp-Lys-Thr—Cys-Thr—OH, Phe-Pen-Phe-D—Trp-Lys-Thr—Pen-Thr—OH; H-D-Phe-Cys—Phe-D—Trp-Lys-Thr-Cys-Thr-ol, H-D-Phe-Cys—Phe-D—Trp-Lys—Thr-Cys-Thr-l\H2, H-D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr- H2, H-D-Trp-Cys—Phe-D—Trp-Lys—Thr-Cys-Thr-1\H2, H-D-Phe-Cys—Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, H-D-Phe-Cys—Tyr-D—Trp-Lys—Val-Cys-Trp-l\H2'7 3 5 H-D-Phe-Cys—Tyr-D-Trp-Lys-Val-Cys-Thr-I\H2, Ac-D-Phe-Lys*-Tyr-D-Trp-Lys-Va1-Asp-Thr-NH2, wherein an amide bridge is between Lys* and Asp; Ac-hArg(Et)2—G1y-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr—NH2; Ac-D-hArg(Et)2-G1y-Cys-Phe—D-Trp-Lys-Thr-Cys—Thr-NHz; Ac-D-hArg(Bu)-G1y-Cys-Phe—D-Trp—Lys-Thr-Cys-Thr-NH ; Ac-D-hArg(Et)2-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr—Hz; Ac-L-hArg(Et)2-Cys-Phe-D-Trp-Lys—Thr-Cys—Thr-NH2; Arg(CH2CF3)2-Cys-Phe-D—Trp-Lys—Thr-Cys—Thr—NH2; Ac-D-hArg(CH2CF3)z-Gly-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr-NH2; Ac-D—hArg(CH2CF3)2-G1y-Cys-Phe-D-Trp-Lys-Thr—Cys-Phe-NHZ; Ac-D-hArg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr-NHEt; Ac-L-hArg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys-Thr—Cys—Thr—NH2; Arg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys(Me)-Thr-Cys-Thr-NH2; Ac-D-hArg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys(Me)-Thr-Cys-Thr-NHEt; Ac-hArg(CH3, hexy1)-G1y-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NHZ; H—hArg(hexyl)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2; Ac-D-hArg(Et)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-RHEt; Ac-D-hArg(Et)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys-Phe-RHz; Propionyl-D-hArg(Et)2-G1y-Cys-Phe—D-Trp-Lys(iPr)—Thr-Cys-Thr-NH2; -Nal-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys-Gly-hArg(Et)2-NH2; Ac-D-Lys(iPr)-G1y-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr-NH2; Ac-D-hArg(CHzCF3)2-D-hArg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys— Thr-NHz; Ac-D—hArg(CHZCF3)2—D-hArg(CH2CF3)2-Gly—Cys—Phe-D-Trp—Lys-Thr-Cys— Phe-NHz; Ac-D—hArg(Et)2-D-hArg(Et)2—G1y-Cys—Phe-D—Trp-Lys-Thr—Cys—Thr—NH2; Ac-Cys-Lys-AsnCl-Phe-Phe-D-Trp-Lys-Thr-Phe—Thr-Ser-D-Cys-NHz; Bmp-Tyr-D-Trp-Lys—Val-Cys—Thr-NH2; Bmp-Tyr-D-Trp-Lys-Val-Cys-Phe-NH2; 3O Bmp-Tyr-D-Trp-Lys—Val-Cys—p-Cl-Phe-NH2; Bmp-Tyr-D-Trp-Lys-Val-Cys-B-Nal-NH2; H—D-B—Nal-Cys—Tyr-D—Trp-Lys—Val-Cys-Thr—NH2; e-Cys-Tyr-D-Trp-Lys-Abu—Cys-Thr-NH2; H—D—Phe-Cys—Tyr-D-Trp-Lys—Abu—Cys—B-Nal—NHZ; H-pentafluoro-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2; Ac-D—B—Nal-Cys-pentafluoro—Phe-D-Trp—Lys—Val-Cys—Thr-NH2; H-D-B—Nal-Cys-Tyr-D-Trp—Lys—Val-Cys—B-Nal-NHZ; H—D-Phe-Cys-Tyr-D—Trp—Lys-Val-Cys-B-Nal-NHZ; H-D-B—Nal-Cys-Tyr-D-Trp—Lys-Abu-Cys—Thr-NHz; H—D-p-Cl-Phe-Cys—Tyr-D-Trp-Lys—Abu—Cys—Thr-NHz; Ac-D-p-C1-Phe-Cys-Tyr-D-Trp-Lys-Abu—Cys-Thr-NH2; H—D-Phe-Cys-B-Nal-D-Trp-Lys-Val-Cys-Thr—NHZ; H-D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2; cyclo (Pro-Phe-D-Trp-N—Me—Lys—Thr-Phe); cyclo (Pro-Phe-D-Trp=Lys-Thr-N—Me-Phe); cyclo Ala-Tyr—D-Trp-Lys-Thr—Phe); cyclo (Pro-Tyr-D-Trp-Lys-Thr-Phe); cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe); cyclo (Pro-Phe-L-Trp—Lys-Thr-Phe); cyclo (Pro-Phe-D-Trp(F)-Lys-Thr-Phe); cyclo (Pro-Phe-Trp(F)-Lys-Thr-Phe); cyclo (Pro-Phe-D-Trp-Lys-Ser-Phe); cyclo (Pro-Phe-D-Trp-Lys-Thr-p-Cl-Phe); cyclo (D-Ala-N-Me-D-Phe-D-Thr-D-Lys-Trp-D-Phe); cyclo (D-Ala-N—Me-D-Phe-D-Va1-Lys-D-Trp-D-Phe); cyclo (D-Ala-N-Me-D-Phe-D-Thr-Lys-D-Trp-D-Phe); cyclo (D-Abu-N—Me-D-Phe-D-Va1-Lys-D-Trp-D-Tyr); cyclo (Pro-Tyr-D-Trp-tAchXAla-Thr-Phe); cyclo (Pro-Phe-D-Trp-tAchXAla-Thr-Phe); cyclo (N—Me-Ala-Tyr—D-Trp—Lys-Val—Phe); cyclo (N-Me-A1a-Tyr-D-Trp—tAchXA1a-Thr-Phe); cyclo (Pro-Tyr—D-Trp—4—Amphe-Thr—Phe); cyclo he-D-TrpAmphe-Thr-Phe); cyclo (N-Me-Ala-Tyr—D-Trp—4—Amphe—Thr-Phe); cyclo (Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba); 3O cyclo (Asn-Phe—Phe-D—Trp-Lys-Thr-Phe-Gaba-Gaba); cyclo (Asn-Phe-D-Trp-Lys-Thr-Phe); cyclo (Asn-Phe—Phe-D—Trp-Lys-Thr-Phe-NH(CH2)4CO); cyclo he-Phe-D-Trp-Lys—Thr-Phe-B-Ala); cyclo (Asn-Phe—Phe-D—Trp-Lys-Thr-Phe-D-Glu)-OH; cyclo (Phe-Phe-D-Trp-Lys-Thr-Phe); cyclo (Phe-Phe—D-Trp—Lys-Thr-Phe-G1y); cycle (Phe-Phe-D—Ti‘p—Lys—Thr—‘Phe-Gaha); cycle (Asn—Pllc—Phc—D—Trp—Lys-Thr—l’he—Gly); cycle (Asn—Pl}c~Phc—D~Trp(F)—Lys—Thr—Phc~Gaba); cycle (ASH4Phe-Phe-D—T1jp(N'Og)-Lys-Thr—Phc-Gaba‘); cycle (Asn—Phc—‘Phe-Trpmr}Lys—Thr—Phc—Gaba); cycle (Asn—’l’hc—Phc—'D-Trp—Lys—Thr—Phe(l)—Gaba); cycle (Asn-Phc-Phc-D—Tm—Lys—Thr—TyxfBut)-Gaba); cycle (Bmp-lcys-Asn—Pl]c-Pllc-D-Trp-l.,ys—Thr-Phe-Thr—Pre-Cys)—OH; cycle (Emp—Lys—Asn-Phc—Phe-D—Trp—LyS-Thr-Phe—Thr—Tpo-Cys)-OH; l 0 cycle (Bmp-Lys—Asn—Phe-Phc-D-Trp—Lys—Thr—Phc-Thr—Mchu-Cys‘)-OH; cycle (Phc-Phc-D-Trp-Lys—Thr—Phc-Phe-Gaha}; cycle (Phe—Phe-D—Trp-Lys—Thr—Phe-D—Phe-Gaba; cycle (Phe-Phe—D-Trp( 5 F)-Lys—Thr—Phe-Phe—Gaba); cycle (Asn-il’hc-Phc-ID-Trp-Lys(_.Ac)-Thr—Phe-‘NH-(CH2)3—CO); cycle (Lys—Phe-Phc-D-T1fip~Lys—Thr—Phc-Gaba); or cycle (Om-Phe-Phe-D-Trp-Il.,ys-Thr-Phc-Gaba); or a pharmaceutically acceptable salt thereof. in one embodiment, the sematestatin agonist is: D~B~Nal~€ys~Tyr~D—T1])~Lys~ThruCysuThruNH:j.

H-C-ys-ZPhe-Phc-D-Tm-I..ys—Thr-Phe-Cys-N'Hg; ‘Ig)-2WN chl'lgmCO—D-Phe-C‘ya-Tyr-D—Trp~Lys—Abu{twine—NH} Homllglg N “u"-((Tllglgu'”SO;-D-Phevas-Tyr-I)-'l'rp-Lye-AlanJigs-Thr-Nllg D—Phe-cyclo(_Cys~Phe-I)~'l7rp-Lys~'I'hr-Cys)-’I’hr~ol; or a phannaccutically acceptable salt thereof.

In anether embodiment, the Somal‘ostatln agonist is: DePhe~cycl0(Cys*Phe~I)'T1‘p«Lys~Thr~Cys)~Thr~el er a. phannaceutically acceptable salt f.

In one embodiment, the c acid s human. GHR. The nucleic acid may have a nucleotide sequence as shown in SEQ ID NO:4 or SEQ {D N025.

In one embodiman the oligonuclectidc is from 12 to 50 nucleobases in length.

In. another embodiment, the eligen'ucleotide is from l5 to 30 bases in length.

In one embodiment, the ucleotide is a DNA oligonucleotide. In another embodiment, the oligonucleotide is a RNA oligonucleotide, for example, a short interfering RNA ). In another embodiment, the oligonucleotide is a chimeric oligonucleotide.

In one embodiment, the oligonucelotide has at least 70% complementarity with the nucleic acid encoding GHR. In r embodiment, the oligonucelotide has at least 80% complementarity with the nucleic acid encoding GHR. In another embodiment, the oligonucelotide has at least 90% complementarity with the nucleic acid encoding GHR. In another embodiment, the oligonucelotide has at least 95% complementarity, for example, 96%, 97%, 98%, or 99% complementarity with the nucleic acid encoding GHR.

In one embodiment, the oligonucelotide comprises at least an 8 consecutive nucleobase portion of SEQ IDNO:6,7,8,9,10,11,12,13,14,15,16,17,18,19,21, 22,23,24,25,26,27,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45, 48,49,50,51,52,53,54,55,56,57,58,60,61,62,63,64,65,66,68,69,70, 73,74,75,76,78,79,80,or81.

In another ment, the oligonucelotide consists of the nucelobase sequence ofSECQHDIvcmz6,7,8,9,10,11,12,13,14,15,16,17,18,19,21,22,23,24,25,26, 27,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50, 51,52,53,54,55,56,57,58,60,61,62,63,64,65,66,68,69,70,71,72,?3,74,75, 76,78,79,80,or81.

In one embodiment, the oligonucleotide consists of the nucleobase sequence of SEQ ID NO:6.

In one embodiment, the oligonucleotide specifically hybridises with a region encoding GHR, wherein the region comprises a translation initiation codon, a ation codon, a coding region, a 5' untranslated region, a 3' untranslated region, an intron:exon junction or an exonzintron junction. In one ment, the region comprises at least an 8 consecutive nucleobase portion of a sequence selected from SEQ ID NOs: 84-154.

In one embodiment, the oligonucleotide comprises at least an 8 consecutive nucleobase portion complementary to a region of SEQ ID NO:4 selected from the group ting of nucleotides 260-339, 332-351 and 344-423 of SEQ ID NO:4.

In one embodiment, the ucleotide inhibits the expression of GHR and/or growth e binding protein (GHBP) by at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,or4596 In one embodiment, the oligonucleotide comprises at least one modified intemucleoside linkage, sugar , or nucleobase. The oligonucleotide may, for example, comprise at least one 2'—O-methoxyethyl sugar moiety and/or at least one phosphorothioate intemucleoside linkage and/or at least one ylcytosine.

In one embodiment, the oligonucleotide consists of 20 linked nucleosides, wherein the oligonucleotide consists of a base of SEQ ID N06; and wherein the oligonucleotide consists of a ten deoxynucleotide region flanked on both the 5' end and the 3’ end of said ten deoxynucleotide region with five 2'-O-(2-methoxyethyl) nucleotides, and wherein each internucleoside linkage in the oligonucleotide is a phosphorothioate linkage, and wherein each cytosine in said oligonucleotide is a 5- methylcytosine.

The present disclosure also provides a method of reducing the level of IGF-I in a subject, the method comprising administering a Somatostatin t in combination with an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid encoding GHR so as to inhibit expression of the GHR, thereby reducing the level of IGF-I in the subject. In one embodiment, the level of serum/plasma IGF-I is reduced.

In one embodiment, the method further comprises fying a subject in need of a reduction in said subject's GHR and/or IGF-I levels, for example serum/plasma IGF-I levels.

The Somatostatin agonist, the GHR and the oligonucleotide may be r characterized by any one of the above features.

The present disclosure also provides for use of a Somatostatin agonist and an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid ng GHR in the manufacture of a ment for the treatment or prevention of a disease caused by and/or associated with an increased level of IGF-I. In one embodiment, the level of serum/plasma IGF-I is reduced.

In one embodiment, the disease is acromegaly, gigantism diabetic retinopathy, diabetic nephropathy, or an IGF-I ve cancer such as prostate, myeloma, lung, breast, or colon cancer. 3O The Somatostatin agonist, the GHR and the oligonucleotide may be further characterized by any one of the above features.

The t disclosure also provides for use of a Somatostatin agonist and an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid encoding GHR in the manufacture of a medicament for ng the level of IGF-I in a subject.

The Somatostatin agonist, the GHR and the ucleotide may be r characterized by any one of the above features.

The present disclosure also provides for a composition comprising a Somatostatin agonist and an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid encoding GHR for the treatment or prevention of a disease caused by and/or ated with an increased level of IGF-I.

The statin agonist, the GHR and the oligonucleotide may be further characterized by any one of the above features.

The present sure also provides for a composition comprising a Somatostatin agonist and an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid encoding GHR for reducing the level of IGF-I in a subject.

The Somatostatin t, the GHR and the oligonucleotide may be further characterized by any one of the above features.

Any embodiment herein shall be taken to apply mutatis mutandis to any other embodiment unless specifically stated otherwise.

The invention is hereinafter described by way of the following non-limiting Examples and with reference to the accompanying Figures.

KEY TO THE SEQUENCE G SEQ ID NO:1 - Somatostatin nucleotide sequence SEQ ID NO:2 - Somatostatin polypeptide sequence SEQ ID NO:3 - Octreotide peptide sequence SEQ ID NO:4 - Human growth hormone receptor (hGHR) cDNA sequence SEQ ID NO:5 - hGHR gene sequence SEQ ID NO:6-83 - Oligonucleotides targeted to hGHR SEQ ID NO:84-154 — Target sequences of hGHR Figure 1 is a graphical representation of data showing reduction in IGF-l levels as a percentage of base line with subjects with galy treated with twice weekly 200mg (400mg/week) ATLl 103 (SEQ ID No 6) antisense ucleotide targeted to the growth hormone receptor (GHR).

DETAILED DESCRIPTION General techniques and ed tions Unless specifically defined ise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ry skill in the art (e.g., in antisense technology, recombinant technology, cell culture, molecular genetics, immunology, immunohistochemistry, protein chemistry, and biochemistry).

Unless otherwise indicated, the recombinant protein, cell culture, and immunological techniques ed in the present disclosure are standard procedures, well known to those skilled in the art. Such techniques are described and explained throughout the literature in s such as, J. Perbal, A Practical Guide to Molecular Cloning, John Wiley and Sons (1984), J. Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring r Laboratory Press (1989), TA. Brown (editor), ial Molecular y: A Practical Approach, Volumes 1 and 2, IRL Press (1991), D.M. Glover and ED. Hames (editors), DNA Cloning: A Practical Approach, Volumes 1-4, IRL Press (1995 and 1996), FM. Ausubel et al. (editors), Current Protocols in Molecular Biology, Greene Pub. ates and Wiley- Interscience (1988, including all updates until present), E. Harlow and D. Lane rs), Antibodies: A Laboratory Manual, Cold Spring r Laboratory (1988), and J .E. Coligan el al. (editors), Current Protocols in Immunology, John Wiley and Sons (including all updates until present).

The term r", for example, "X and/or Y" shall be understood to mean either "X and Y" or "X or Y" and shall be taken to provide explicit support for both meanings or for either meaning.

As used , "about" or "approximately" shall generally mean within 20%, more preferably within 10%, and even more preferably within 5%, of a given value or range.

Throughout this specification the word se", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated t, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, composition of matter, group of steps or group of compositions of matter shall be taken to encompass one and a ity (i.e. 3O one or more) of those steps, compositions of matter, group of steps or group of compositions of matter.

Abbreviations B-Nal = B-naphthylalanine B-Pal = B-pyridylalanine hArg(Bu) = N—guanidino-(butyl)-homoarginine hArg(Et)2 = N,N'-guanidino-(diethyl)-homoarginine hArg(CH2CF3)2 = N,N'-guanidino-bis-(2,2,2,-trifluoroethyl)—homoarginine hArg(CH3, hexyl) = N,N'-guanidino-(methyl, hexyl)—homoarginine Lys(Me) = NE-methyllysine Lys(iPr) = N-isopropyllysine AmPhe = aminomethylphenylalanine AchXAla = aminocyclohexylalanine Abu = (x-aminobutyric acid Tpo = proline MeLeu = N—methylleucine Orn = ornithine Nle = norleucine Nva = norvaline Trp(Br) = 5-brorno-tryptophan Trp(F) = o-tryptophan Trp(NOz) = 5-nitro-tryptophan Gaba = y-aminobutyric acid Bmp = B-mercaptopropionyl Ac = acetyl Pen = pencillamine.

Treatment and prevention of IGF-I positive diseases The present invention provides methods useful in the tion and/or treatment of a disease, disorder, or condition caused by n-like growth factor I (IGF-I) and/or associated with an increased level of insulin-like growth factor I (IGF-I).

As used herein, the term "treatment" refers to administering a pharmaceutical composition to effect an alteration or improvement of a e, disorder, or condition.

As used herein, the term "prevention" refers to stering a pharmaceutical composition to stop or hinder the development of at least one symptom of a disease, 3O disorder, or condition. The subject targeted for treatment is a mammal, preferably a human. As used herein, "an increased level of n-like growth factor I (IGF-I)" includes a level above the normal range or in the normal range, for example, at the high end of the normal range, adjusted for age and sex.

The methods involve administration of a Somatostatin analog having Somatostatin receptor agonistic activity and an oligonucleotide targeted to growth hormone or (GHR) to a subject. The "subject" can be any mammal, preferably a WO 97938 human. Although not wishing to be limited to the theory, the ucleotide acts to inhibit GHR sion in said subject, whilst the Somatostatin agonist acts to prevent production of GH, reducing GH binding to the GHR, thereby reducing the level of IGF- I (which is produced in response to GH ling) in the subject. Insulin-like growth factor I is a ubiquitous polypeptide important in proliferation, having potent mitogenic s on a broad range of cells, and important in cell survival, regulating apoptosis on a broad range of cells.

Although not wishing to be limited to theory, the antisense oligonucleotide ts GHR expression at the RNA level whilst the Somatostatin agonist may se GHR or growth hormone binding protein (GHBP) or both. In one embodiment, the oligonucleotide also acts to reduce GHBP expression. The GHBP is the soluble extracellular portion of the GH receptor, derived by alternative mRNA splicing of the mRNA transcript (in for example, mice and rats) or proteolytic cleavage of the GHR (in for example, humans, cows and pigs). The GHBP may bind GH, increasing the half life of GH, and increasing GH action.

In one embodiment, the ent reduces or prevents occurrence of one or more symptoms of acromegaly, for e, reducing the increased serum IGF-I levels in acromegaly to normal levels, or reducing soft tissue swelling, ement of internal organs, extremities like overgrowth of the jaw, enlargement of hands and feet, deepening of the voice, thickening of skin, offensive body odor, articular cartilage problems, hyperphosphatemia, peripheral neuropathies, higher blood pressure, diabetes, heart disease, and cancer.

In another ment, the treatment reduces or prevents occurrence of one or more symptoms of retinopathy, for example, reducing new blood vessel formation and/or edema, d, double, or distorted vision, or difficulty reading, floaters or spots in vision, loss of vision or a shadow or veil across field of vision, pain, pressure, or constant redness of the eye.

In another embodiment, the treatment reduces or prevents occurrence of one or more symptoms of diabetic nephropathy, for example ula filtration, 3O microalbuminuria, nuria, renal damage, swelling in the legs, nausea and vomiting, malaise, fatigue, headache, itching, frequent hiccups, unintended weight loss, swelling of the face, unintended weight gain due to fluid buildup, and high blood pressure.

In another embodiment, the treatment reduces the size and/or growth of a tumor or cancer (such as prostate, myeloma, lung, breast, or colon cancer) and/or delays progression of the tumor or cancer (such as prostate cancer) from androgen responsive/dependent to androgen unresponsive/independent. Tumor or cancer size and/or growth may be reduced, for example, by reducing the eration rate of the tumor/cancer cells, increasing the apoptotic rate of the tumor/cancer cells, modulating tumor/cancer cell signaling, chemosensitization, and/or inhibiting adhesion, anchorage, metastasis of the tumor/cancer cells and/or transformation of cells, for e, prostate cells. The treatment may, for example, reduce IGF-I levels at the high end of the normal range to lower levels, and/or from the top quartile to the 2““1 quartile, 3rd or 4th quartile, and/or from the 2nd le to the 3rd or 4th quartile as adjusted for age and sex. The treatment may reduce endocrine, autocrine or ine levels of IGF-I as antisense oligonucleotides and the Somatostatin agonist may work in the tissues.

Somatostatin and its agonists Somatostatin (somatotropin release inhibiting factor or SRIF) has both a 14 amino acid isoform (somatostatin-l4) and a 28 amino acid m (somatostatin-28) (See Wilson, J. & Foster, D., Williams Textbook of Endocrinology, p. 510 (7th ed., 1985)). The compound is an inhibitor of secretion of the growth hormone and was originally isolated from the hypothalamus (Brazeau et al., 1973). Native somatostatin has a very short on of effect in vivo since it is rapidly inactivated by endo- and exopeptidase. Many novel analogs have been prepared in order to enhance the duration of effect, biological activity, and selectivity (e. g., for the particular somatostatin receptor) of this hormone. Such analogs will be called ostatin ts" herein.

Further, compounds that are short peptides modified by organic moieties and non- peptides, such as organic molecules that do not have an art-recognized amino acid as part of its structure, that bind to somatostatin receptor(s) are also within the meaning of "somatostatin agonists". s somatostatin receptors (S STRs) have been isolated, for example, SSTR- l, SSTR-2, SSTR-3, SSTR-4, and SSTR-5. Thus, the somatostatin agonist may be a SSTR-1 agonist, SSTR-2 agonist, SSTR-3 agonist, SSTR-4 t of a SSTR-5 agonist. Preferably, the SSTR t has a high y (e.g., Ki of less than 1 nM or, preferably, of less than 10 nM) for the SSTR. The somatostatin agonist may also be 3O selective for a particular somatostatin receptor, for example, have a higher binding affinity for a particular somatostatin receptor subtype. Preferably the somatostatin agonist when used in the treatment of acromegaly or gigantism is more ive for SSTR-2, like Octreotide, or Lanreotide, or binds SSTR-1,2,3 and 5 like Pasireotide.

Somatostatin agonists which can be used in the s of the present invention, but are not limited to, those covered by formulae or those specifically recited in the publications set forth below, all of which are hereby incorporated by reference: EP Application No. 25 164 EU; Van Binst et a1. Peptide Research (1992) 5:8; Horvath, A. et al. Abstract, "Conforrnations of Somatostatin Analogs Having Antiturnor Activity", 22nd European peptide Symposium, Sep. 13-19, 1992, Interlaken, Switzerland; PCT Application WO 91/09056 (1991); EP Application 0 363 589 A2 (1990); US. Pat. \o. 642 (1990), US. Pat. \0. 4,871,717 (1989); US. Pat. \o. 4,853,371 (1989); US. Pat. \o. 4,725,577 ; US. Pat. \o. 4,684,620 (1987) US. Pat. \o. 4,650,787 (1987); US. Pat. \o. 4,603,120 (1986); US. Pat. \o. 4,585,755 (1986); EP Application 0 203 031 A2 (1986); US. Pat. \o. 4,522,813 (1985); US. Pat, \o. 486,415 (1984); US. Pat. \o. 4,485,101 ; US. Pat. Ro. 385 (1984); US. Pat. \o. 4,395,403 (1983); US. Pat. )0. 4,369,179 (1983); US. Pat. \o. 4,360,516 (1982); US. Pat. )0. 4,358,439 (1982); US. Pat. \o. 4,328,214 (1982); US. Pat. R0. 4,316,890 ; US. Pat. \o. 4,310,518 (1982); US. Pat. R0. 4,291,022 ; US. Pat. \o. 4,238,481 (1980); US. Pat. R0. 4,235,886 (1980); US. Pat. \o. 4,224,190 (1980); US. Pat. )0. 4,211,693 (1980); US. Pat. \0. 4,190,648 (1980); US. Pat. )0. 4,146,612 ; and US. Pat. \0. 4,133,782 (1979).

Examples of somatostatin agonists e, but are not limited to, the following somatostatin analogs and pharrnaceutically acceptable salts thereof which are disclosed in the above-cited references: D-B—Nal-Cys—Tyr-D—Trp-Lys—Thr—Cys-Thr—NHz; D-Phe—Cys-Phe-D-Trp-Lys-Thr-Cys—B-Nal-NHz; D-Phe—Cys-Tyr-D-Trp-Lys—Thr-Cys—B-Nal-NH2; l-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr-NHz; D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr—NHz; D-Phe-Cys-Phe-D-Trp-Lys-Thr-Pen-Thr-NHz; D-Phe—Cys—Tyr-D-Trp-Lys-Thr-Pen-Thr—OH; D-Phe-Cys-Phe-D-Trp-Lys-Thr-Pen-Thr-OH; Gly-Pen-Phe-D-Trp-Lys-Thr—Cys-Thr-OH; n-Tyr-D-Trp-Lys-Thr—Cys-Thr-OH; Phe-Pen-Phe-D-Trp-Lys-Thr—Pen-Thr-OH; H-D-Phe-Cys—Phe-D-Trp-Lys-Thr-Cys-Thr-ol; H—D-Phe-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr- 'Hz; H-D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr- H2; H-D-Trp-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr-1\H2; H-D-Phe-Cys—Tyr-D-Trp-Lys-Val-Cys-Thr- VH2; H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-l\H2; H-D-Phe-Cys—Tyr-D-Trp-Lys-Val-Cys-Thr-NH2; he-Lys*-Tyr-D-Trp-Lys-Val-Asp-Thr-NH2 (an amide bridge formed between Lys* and Asp); Ac-hArg(Et)2Gly-Cys—Phe-D—Trp-Lys—Thr-Cys-Thr—NHZ; Ac-D-hArg(Et)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NHz; Ac-D—hArg(BU)-Gly—Cys-Phe—D-Trp—Lys-Thr—Cys-Thr-NHZ; Ac-D-hArg(Et)2-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2; Ac-L—hArg(Et)2-Cys—Phe-D-Trp-Lys—Thr-Cys—Thr-NH2; Ac-D-hArg(CH2CF3)2-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2; 3O Ac-D—hArg(CH2CF3)2—Gly-Cys-Phe—D—Trp-Lys-Thr—Cys-Thr—NH2; Ac-D-hArg(CH2CF3)2-Gly-Cys-Phe—D-Trp-Lys-Thr—Cys-Phe-NHz; Arg(CH2CF3)2—Gly-Cys-Phe—D-Trp-Lys-Thr—Cys-Thr—NHEt; Ac-L-hArg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys-Thr—Cys-Thr—NH2; Ac-D—hArg(CH2CF3)2—Gly-Cys-Phe—D-Trp-Lys(Me)—Thr-Cys-Thr-NH2; Ac-D-hArg(CH2CF3)2-Gly-Cys-Phe—D-Trp-Lys(Me)-Thr-Cys-Thr-NHEt; Ac-hArg(CH3, hexyl)—Gly-Cys-Phe-D—Trp-Lys-Thr—Cys-Thr—NH2; H-hArg(hexyl)2-Gly-Cys-Phe-D-Trp—Lys-Thr-Cys-Thr-NH ; Ac-D—hArg(Et)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys—Thr-NHEt; Ac-D—hArg(Et)2-G1y-Cys-Phe-D-Trp-Lys-Thr-Cys-Phe-NH2; Propionyl-D—hArg(Et)2-G1y—Cys—Phe-D-Trp-Lys(iPr)—Thr—Cys—Thr—NHz; Ac-D—B-Nal-Gly-Cys—Phe-D-Trp-Lys-Thr-Cys-Gly-hArg(Et)2-NH2; ys(iPr)-G1y-Cys-Phe-D-Trp-Lys-Thr—Cys—Thr-NH2; Arg(CH2CF3)z-D-hArg(CH2CF3)2-Gly-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2; Ac—D—hArg(CH2CF3)2-D-hArg(CH2CF3)2-Gly-Cys—Phe-D—Trp-Lys-Thr-Cys-Phe—NHz; Ac-D—hArg(Et)2-D-hArg(Et)2-G1y-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NHZ; Ac-Cys—Lys—Asn-4—Cl-Phe-Phe-D-Trp-Lys—Thr-Phe-Thr—Ser—D-Cys-NHZ; Bmp-Tyr-D-Trp-Lys—Val-Cys-Thr-NH2; Bmp-Tyr-D-Trp-Lys-Val-Cys-Phe-NH2; r-D-Trp-Lys-Val-Cys-p-C1-Phe-NH2; Bmp-Tyr-D-Trp-Lys-Val-Cys-B-Nal-NHZ; H-D-B-Nal-Cys-Tyr-D-Trp-Lys—Val-Cys-Thr—NHz; H—D-Phe-Cys-Tyr-D-Trp-Lys-Abu-Cys-Thr-NHZ; H-D-Phe-Cys—Tyr-D-Trp-Lys-Abu—Cys-B-Nal-NHz; H-pentafluoro-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NHQ; Ac-D-B-Na1-Cys-pentaflu0r0-Phe-D-Trp-Lys—Val-Cys—Thr-NHz; H-D-B-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-B-Nal-NHZ; H-D-Phe-Cys—Tyr-D-Trp-Lys-Val-Cys-B-Nal-NHz; H—D-B—Nal-Cys—Tyr-D—Trp-Lys—Abu—Cys-Thr—NHZ; H-D-p-Cl-Phe-Cys-Tyr-D-Trp-Lys-Abu—Cys—Thr-NH2; Ac-D—p—Cl-Phe—Cys-Tyr-D-Trp—Lys—Abu-Cys—Thr-NHZ; H-D-Phe-Cys—B-Nal-D-Trp-Lys—Val-Cys-Thr—NHz; H—D-Phe-Cys—Tyr-D—Trp-Lys—Cys-Thr—NH2; cyclo (Pro-Phe-D-Trp-N-Me-Lys-Thr-Phe); cyclo (Pro-Phe—D-Trp—Lys-Thr—N—Me—Phe); cyclo (N-Me—A1a-Tyr-D-Trp—Lys-Thr-Phe); 3O cyclo (Pro-Tyr—D-Trp—Lys-Thr—Phe); cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe); cyclo (Pro-Phe—L-Trp—Lys-Thr—Phe); cyclo (Pro-Phe-D-Trp(F)-Lys-Thr-Phe); cyclo (Pro-Phe—D-Trp—Lys-Ser-Phe); cyclo (Pro-Phe-D-Trp-Lys-Thr-p-C1-Phe); cyclo (D-Ala—N—Me-D—Phe-D—Thr-D—Lys-Trp—D-Phe); WO 20141197938 cyclo (D-Ala—N—Me-D-Phe-D-Va1-Lys-D-Trp-D-Phe); cyclo (D-Ala—N—Me—D-Phe-D-Thr-Lys-D-Trp-D-Phe); cyclo (D-Abu-N—Me-D-Phe-D-Va1-Lys-D-Trp-D-Tyr); cyclo (Pro-Tyr-D-Trp-tActh1a—Thr—Phe); cyclo (Pro-Phe-D-Trp-tAchXAla-Thr-Phe); cyclo (N—Me-Ala-Tyr—D-Trp—Lys-Val-Phe); cyclo (N—Me-Ala-Tyr-D-Trp—tAchXAla-Thr-Phe); cyclo (Pro-Tyr-D-TrpAmphe-Thr—Phe); cyclo (Pro-Phe-D-TrpAmphe-Thr—Phe); cyclo (N—Me-Ala-Tyr—D-TrpAmphe-Thr—Phe); cyclo (Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba); cyclo (Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba-Gaba); cyclo (Asn-Phe-D-Trp-Lys-Thr-Phe); cyclo (Asn-Phe-D-Trp-Lys-Thr-Lys-Thr-Phe-NH(CH2)4CO); cyclo (Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-B-Ala; cyclo (Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-D-Glu)-OH; cyclo (Phe-Phe-D-Trp-Lys-Thr-Phe); cyclo Phe-Phe-D-Trp-Lys-Thr-Phe-Gly); cyclo (Phe-Phe-D-Trp-Lys-Thr-Phe-Gaba); cyclo (Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Gly); cyclo (Asn-Phe-Phe-D-Trp(F)-Lys-Thr-Phe-Gaba); cyclo (Asn-Phe-Phe-D-Trp(N02)-Lys-Thr-Phe-Gaba) cyclo (Asn-Phe-Phe-Trp(Br)-Lys-Thr-Phe-Gaba); cyclo he—Phe-D—Trp-Lys-Thr—Phe(I)-Gaba); cyclo he-Phe-D-Trp-Lys-Thr-Tyr(But)—Gaba); cyclo (Bmp-Lys-Asn—Phe-Phe—D-Trp—Lys-Thr—Phe-Thr-Pro—Cys)—OH; cyclo (Bmp-Lys-Asn-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-Tpo-Cys)—OH; cyclo (Bmp-Lys-Asn—Phe-Phe—D-Trp—Lys-Thr—Phe-Thr-MeLeu—Cys)—OH; cyclo (Phe-Phe-D-Trp-Lys-Thr-Phe-Phe-Gaba); 3O cyclo (Phe-Phe—D-Trp—Lys-Thr-Phe-D—Phe-Gaba); cyclo (Phe-Phe-D-Trp(5F)—Lys-Thr-Phe-Phe-Gaba); cyclo (Asn-Phe-Phe-D—Trp-Lys(Ac)—Thr-Phe—NH—(CH2)3-CO); cyclo he-Phe-D-Trp-Lys-Thr—Phe-Gaba); cyclo (Om-Phe-Phe-D—Trp-Lys-Thr—Phe-Gaba); and H-Cys-Phe-Phe-D-Trp-Lys-Thr-Phe-Cys-NHz.

Note that for all somatostatin agonists described herein, each amino acid residue represents the stiucture of R)H—CO—, in which R is the side chain (e.g., CE; for Ala) except for Theo} which means -N H~CH(CH(CH3)OH)—CH3—OH and Pro which means pt‘oiinyi. lines n amino acid residues represent peptide bonds whichjoitt the amino acids. Also, where the amino acid residue is optically active, it is the L—form configuration icon that is ed unless D-t‘orm is expi'essiy designated. A de bridge is formed between two Cys residues; however, it is not shown.

Use of linear somatostatin agonists of the ing formula is also within the in vention: 'l 0 Ale-anl—mt—o-Trp—I,..ys-A.°--A'—-~A8~R3...i M. or a pharmaceuticaily acceptable salt thereof, w'ltetein A‘ is a D- or L-isomei‘ of Ala, Leu, lle, Val, Nle, Tin: Set, B-Nai, B-Pai, ’I'rp, Phe, 2,4—dichloro—Phe, pentafluorwi’he, p—X—Phe, or o—X—Phe; '15 A2 is Ala, Len, lie, Val, Nie, Pile, BuNal, pyridyi~Aia, Ttp, 2,4~dichioro~Phe, pentatl'uoro—Phe, e, 0.1‘p~X-Ph€; A3 is pyridyl-Ala, 'l‘rp, 'Phe, B-Nal, 2,4-dichloro-Phe, pentafluoro-Phe, o-X-Phe, or p—X»Phe; A6 is Vat, Ain, Len, lie, Nie, Thr, Abe, or Set; A? is Ala, Len, Ile, Val, Nle, Phe, B—Nal, pyridyiwAia, 'i‘rp, 2,4~dichioro-Phe, pentatiuoro—Phe, o-X—Phe, or e; A8 is a, D or bisomer ofAla, Leu, 116, Vai, Nie, Thr, Set, Phe, B~Nal, pyridyi— Aia, Trp, 2,4»diehiom-Phe, pentafluoro-Phe, p-X—Phe, or o—lX-Phe; wherein X for each occurrence is independently selected from the group [‘9 (J) consisting of CH3, Ci, Br, F, OH, OCH} and N02; each R1 and R3, independently, is H, tower acyl or lower alkyl; and R3 is OH or NHQ; provided that at least one ofA1 and A8 and one of A2 and A? must be an aromatic amino acid; and further provided that AA], AE, A7 and A8 cannot all be aromatic amino acids.

Exampies of linear agonists to be used in the method ofthis invention include: H-D~Phe-p—chiero-Phe~Tyr—D~Ttp—I.,ys«Tilt—Phe-Thr-NHg; HJD—Phe—p—NO2—Plie~Tyr—D—Trp—Lys—Vai—Phe-ThrL—NH3; H—D—Naiwp-el1ioro—Phe~Tyr-D«Ttp-Lys—Val“Phe~Thr~NHg; H-D-Phe-Plie-Phe—D-Trp-Lys—Thr—Phe—Tlxr—‘NH';; H—D—Plie—Phe-Tyr—D—Trp— Ly’s—Val-‘Phe—Thr—NH3; H~D—Phe-p~chlor0~Phe—Tyr—D—Trp—Lys-Val~Phe—Thr—NH3; and H-D~PheuAla»Tyi‘-D~T,rpull,ys~\l’al~\r’al~Aia.~[3~D~Nai~Nl-l2; or a phamiaceutically able salt thereof.

If desired, one or more chemical moieties, for exmaple, a sugar derivative, mono— or poly-hydroxy (32—12 alkyl, mono or poly—hydroxy C242 acyi groups, or a piperazine derivative, can be attached to the somatostatin t, e.g., to the N— terminus amino acid. See PCT Application WO 88.102756. European Application 0 329 if.) 295, and PCT Application No. W0 752. An e of a somatostatin agonists which contain N-temiinal chemical substitutions are: HOQCngz— ; i N—(GHQ—CODPhe«Phe~Phe~D«T1p«Lys«"l‘hr«Phe~’I‘hr~NHg: 1-10(<::H2)3——— I)N———- (C3123)3—-S(32~I,)~I’he—Phe—F l1 c-i>—'1'zp~i_.ys:i‘m— eke—Tm—Niig; maria}: N N—(Cng—czo-D—Phe—Cys-fryrm[prim-Lys—Abu-Cys—Tm-NHZ {RIM—233.90); and HO((IIH§}3— N—' (CH-g); SOTDvPhe-Cst1"yr-D—"I‘rp—Lye~Abu~Cye—Thr—NH3 or a ceutically acceptable sali thereof.

In one embodiment, the Somatostaiin agonist is far example- Octreotide, Lanreotide, or Pasireotide. in, a fun'lier embodiment, the Somatostatin agonist is a 10119; acting release (LAR) form, for e, Och‘eotide—LAR (SandostatiiiiI‘M—VLAR), Lanreoiide-LAR (Lanreotide Autogel), or fiPasireotideéLAR, or is Lanreoiide artieles.

Synthesis of Somatostatin agonists The methods for synthesizing somatostal‘in agonists are well documented and are within the ability of a person of ry skill in the art, for example, as illustrated in the U.8. Patents and other references cited hereinabeve.

Synthesis of short amino acid sequences is well established in the peptide art.

For example, synthesis of D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr—NH2, described above, can be synthesized by following the protocol set forth in US. Pat. No. 4,853,371 and synthesis of H—D—Phe-Phe-Phe-D-Trp-Lys-Thr—Phe-Thr—NH2, described above, can be achieved by following the protocol set forth in example I of European Patent ation 0 395 417 A1. The synthesis of somatostatin agonists with a tuted N- terrninus can be achieved, for example, by following the protocol set forth in WO 88/02756, European Pat. Application No. 0 329 295, and PCT Publication No. WO 94/04752.

Conjugates Somatostatin agonists useful in the methods of the present disclosure may be covalently attached (hereinafter "conjugated") to one or more chemical groups. Such conjugation produces a Somatostatin agonist conjugate having a greater actual molecular weight than the unmodified Somatostatin agonist.

A variety of methods for ting proteins have been described (see, for example, US 337), disclosing the ation of a number of hormones and enzymes to PEG and opylene glycol to produce physiologically active non- immunogenic compositions. Generally, a PEG having at least one terminal hydroxy group is reacted with a coupling agent to form an activated PEG having a terminal reactive group. This reactive group can then react with the (x- and s—amines of proteins to form a covalent bond. Conveniently, the other end of the PEG molecule can be "blocked" with a non-reactive chemical group, such as a methoxy group, to reduce the formation of osslinked complexes of n molecules.

A composition containing a pegylated Somatostatin agonist for use in a therapeutic formulation can be heterogeneous or homogeneous, i.e., ning multiple or single pegylated Somatostatin agonists. Typically, the ition ns at least 70% one or two forms of pegylated statin agonists; preferably, at least 80% one or two forms; and more preferably, at least 90% one or two forms. nse compounds to Growth Hormone Receptor The s of the present disclosure rely on the use of an antisense compound to growth hormone receptor (GHR) to modulate growth hormone (GH) signalling or the GH/insulin—like growth factor-I (IGF-I) axis, particularly the expression of GHR and/or IGF-I. Preferably, the antisense compound is an oligonucleotide. However, other oligomeric antisense compounds, including but not limited to oligonucleotide mimetics are contemplated.

Hybridization of an antisense compound with its target nucleic acid is generally ed to as ense". Hybridization of the antisense compound with its target nucleic acid inhibits the function of the target nucleic acid. Such "antisense inhibition" is typically based upon hydrogen bonding-based hybridization of the antisense compound to the target nucleic acid such that the target nucleic acid is cleaved, degraded, or otherwise rendered inoperable. The functions of target DNA to be interfered with can include replication and transcription. Replication and transcription, for e, can be from an endogenous cellular template, a vector, a d construct or otherwise. The functions of RNA to be interfered with can include functions such as translocation of the RNA to a site of protein translation, translocation of the RNA to sites within the cell which are distant from the site of RNA synthesis, translation of protein from the RNA, splicing of the RNA to yield one or more RNA species, and tic activity or complex formation involving the RNA which may be engaged in or facilitated by the RNA.

"Hybridization" as used herein means pairing of complementary bases of the oligonucleotide and target nucleic acid. Base pairing typically involves hydrogen bonding, which may be -Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases (nucleobases).

Guanine (G) and cytosine (C) are examples of mentary nucleobases which pair through the formation of 3 hydrogen bonds. Adenine (A) and e (T) are examples of complementary nucleobases which pair h the formation of 2 hydrogen bonds. Hybridization can occur under varying circumstances.

A "nucleoside" is a base-sugar combination. The base portion of the nucleoside is normally a heterocyclic base. The two most common classes of such cyclic bases are the purines and the dines. "Nucleotides" are nucleosides that further include a phosphate group covalently linked to the sugar portion of the nucleoside. For those nucleosides that include a pentofuranosyl sugar, the phosphate group can be 3O linked to either the 2', 3' or 5’ hydroxyl moiety of the sugar.

"Specifically hybridizable" and "complementary" are terms which are used to indicate a sufficient degree of mentarity such that stable and specific binding occurs between the antisense compound and target nucleic acid. It is understood that the antisense compound need not be 100% complementary to its target nucleic acid sequence to be specifically izable. An antisense compound is specifically hybridizable when binding of the antisense compound to the target nucleic acid interferes with the expression of the target nucleic acid and there is a sufficient degree of complementarity to avoid non-specific binding of the antisense compound to non- target ces under conditions in which specific binding is desired, for example, under physiological conditions in the case of therapeutic treatment.

The term "stringent hybridization conditions" or "stringent conditions" as used herein refers to conditions under which the antisense compound will ize to its target sequence, but to a minimal number of other ces. Stringent conditions are sequence-dependent and will be different in different circumstances. Stringent condition under which the antisense compound hybridizes to a target sequence is determined by the nature and composition of the antisense compound and the assays in which it is being investigated.

"Complementary" as used , refers to the capacity for precise pairing between a nucleobase of the antisense compound and the target nucleic acid. For example, if a nucleobase at a certain position of the antisense compound is e of en bonding with a nucleobase at a certain position of the target nucleic acid, then the on of hydrogen bonding between the antisense compound and the target c acid is considered to be a complementary position. The antisense compound may hybridize over one or more segments, such that intervening or adjacent ts are not involved in the hybridization event (e.g., a loop structure or hairpin structure).

In one embodiment, the antisense compound ses at least 70% sequence complementarity to a target region within the target nucleic acid. For example, an antisense compound in which 18 of 20 nucleobases are complementary to a target region within the target nucleic acid, and would therefore specifically hybridize, would represent 90% complementarity. In this example, the remaining noncomplementary nucleobases may be red or interspersed with complementary nucleobases and need not be contiguous to each other, or to complementary nucleobases. As such, an antisense compound which is 18 nucleobases in length having 4 non-complementary nucleobases which are flanked by 2 regions of complete complementarity with the target nucleic acid would have 77.8% overall complementarity with the target nucleic 3O acid and would thus, fall within the scope of the present disclosure. Percent complementarity of an antisense compound with a region of a target nucleic acid can be ined routinely using BLAST programs (basic local ent search tools) and PowerBLAST programs known in the art (Altschul el al., 1990, Zhang and Madden, 1997) WO 97938 Antisense oligonucleotides The present disclosure provides for use of an antisense oligonucleotide for inhibiting expression of a growth hormone receptor (GHR), The term "inhibits" as used herein means any measurable decrease (e.g., 10%, %, 50%, 90%, or 100%) in GHR sion.

As used herein, the term "oligonucleotide" refers to an oligomer or polymer of RNA or DNA or mimetics, chimeras, analogs and gs thereof. This term includes oligonucleotides ed of naturally occurring nucleobases, sugars and covalent internucleoside (backbone) linkages, as well as ucleotides having non- naturally occurring portions which function similarly. Such d or substituted oligonucleotides are often preferred over native forms because of desirable properties such as, for example, enhanced cellular uptake, ed affinity for the target nucleic acid and increased ity in the presence of nucleases.

In forming oligonucleotides, phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound. In turn, the respective ends of this linear polymeric compound can be further joined to form a circular compound, however, linear compounds are generally preferred. In on, linear compounds may have internal nucleobase complementarity and may therefore fold in a manner so as to produce a fully or partially double-stranded compound. With regard to ucleotides, the phosphate groups are commonly referred to as forming the internucleoside backbone of the oligonucleotide. The normal linkage or backbone ofRNA and DNA is a 3' to 5' phosphodiester linkage.

Antisense ucleotides useful in the methods of the t disclosure include, for e, ribozymes, siRNA, external guide sequence (EGS) oligonucleotides, alternate splicers, primers, probes, and other oligonucleotides which hybridize to at least a portion of the target nucleic acid.

Antisense oligonucleotides may be administered in the form of single-stranded, double—stranded, circular or hairpin and may contain structural elements such as internal or terminal bulges or loops. Once administered, the antisense oligonucleotides may elicit the action of one or more enzymes or ural proteins to effect modification of the target nucleic acid.

One non-limiting example of such an enzyme is RNAse H, a cellular endonuclease which cleaves the RNA strand of an RNAzDNA duplex. It is known in the art that single-stranded antisense compounds which are "DNA—like" elicit RNAse H. Activation of RNase H therefore results in cleavage of the RNA target, thereby greatly enhancing the efficiency of oligonucleotide-mediated inhibition of gene expression. Similar roles have been postulated for other ribonucleases, such as those in the RNase III and ribonuclease L family of enzymes.

The uction of double-stranded RNA (dsRNA) les, has been shown to induce potent and specific antisense-mediated reduction of the function of a gene or its associated gene products. This enon occurs in both plants and animals and is believed to have an evolutionary connection to viral defense and transposon silencing.

The first evidence that dsRNA could lead to gene silencing in animals came in 1995 from work in the nematode, Caenorhabdilis elegans (Guo and us, 1995).

Montgomery et a]. (1998) have shown that the primary interference effects of dsRNA are posttranscriptional. The posttranscriptional antisense mechanism defined in habditis elegans resulting from exposure to double-stranded RNA (dsRNA) has since been designated RNA interference (RNAi). This term has been generalized to mean antisense-mediated gene silencing involving the uction of dsRNA leading to the sequence-specific reduction of endogenous targeted mRNA levels (Fire et al., 1998). It has been shown that it is, in fact, the single-stranded RNA oligomers of antisense polarity of the dsRNAs which are the potent inducers of RNAi (Tijsterman el al., 2002).

A person having ordinary skill in the art could, without undue experimentation, identify antisense oligonucleotides useful in the methods of the present disclosure.

Modified internucleoside linkages (backbones) Antisense compounds useful in the s of the present disclosure include oligonucleotides having modified nes or non—natural internucleoside linkages.

Oligonucleotides having modif1ed backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. ed oligonucleotide backbones ning a phosphorus atom therein include, for example, phosphorothioates, chiral phosphorothioates, orodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other 3O alkyl phosphonates including 3'—alkylene phosphonates, 5’—alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'—amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, phosphates, and boranophosphates having normal 3'-5' es, 2'-5‘ linked analogs of these, and those having inverted polarity wherein one or more internucleotide linkages is a 3' to 3', 5' to ' or 2' to 2' linkage.

Oligonucleotides having inverted polarity comprise a single 3' to 3' linkage at the 3'-most internucleotide linkage, that is, a single inverted nucleoside residue which may be abasic (the nucleobase is missing or has a hydroxyl group in place thereof).

Various salts, mixed salts and free acid forms are also included.

Representative United States patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, US 3,687,808, US 4,469,863, US 4,476,301, US 5,023,243, US 5,177,196, US 5,188,897, US 423, Us 5,276,019, Us 5,278,302, US 5,286,717, US 5,321,131, US 5,399,676, Us ,405,939, US 5,453,496, US 5,455,233, US 5,466,677, US 5,476,925, US 5,519,126, US 5,536,821, Us 5,541,306, US 5,550,111, US 5,563,253, US 5,571,799, Us ,587,361, US 5,194,599, US 5,565,555, US 5,527,899, US 5,721,218, US 5,672,697 and US 050.

Modified oligonucleotide nes that do not e a phosphorus atom therein include, for example, backbones formed by short chain alkyl or cycloalkyl intemucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic intemucleoside linkages. These e those having morpholino linkages d in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and e backbones; formacetyl and thioformacetyl backbones, methylene etyl and thioformacetyl nes; riboacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; ate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts.

Representative United States patents that teach the preparation of the above oligonucleotides include, but are not d to, US 5,034,506, US 5,166,315, US ,185,444, US 5,214,134, US 5,216,141, US 5,235,033, US 5,264,562, US 5,264,564, US 5,405,938, US 5,434,257, US 5,466,677, US 967, US 5,489,677, US ,541,307, US 5,561,225, US 5,596,086, US 5,602,240, US 5,610,289, US 5,602,240, US 5,608,046, US 5,610,289, US 5,618,704, US 5,623,070, US 5,663,312, US 3O 5,633,360, US 437, US 5,792,608, US 5,646,269 and US 5,677,439.

Modified sugar and cleoside linkages Antisense compounds useful in the methods of the present disclosure include oligonucleotide mimetics Where both the sugar and the intemucleoside linkage (i.e. the backbone) of the nucleotide units are ed with novel groups. The nucleobase units are maintained for hybridization with the target nucleic acid.

An oligonucleotide c that has been shown to have excellent hybridization properties is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar—backbone of an oligonucleotide is replaced with an amide containing backbone, in particular, an aminoethylglycine ne. The nucleobases are retained and are bound ly or indirectly to aza nitrogen atoms of the amide portion of the backbone.

Representative United States patents that teach the preparation of PNA compounds include, but are not d to, US 5,539,082, US 5,714,331, and US 5,719,262.

Further teaching of PNA compounds can be found in Nielsen et al., 1991.

The antisense nds useful in the methods of the present disclosure also include oligonucleotides with phosphorothioate backbones and oligonucleotides with heteroatom backbones, for example, -CH2-NH-O-CH2-, -CH2-N(CH3)-O-CH2- [known as a methylene (methylimino) or MMI backbone], -CH2-O-N(CH3)—CH2-, -CH2- N(CH3)-N(CH3)-CH2- and -O-N(CH3)-CH2-CH2- [wherein the native phosphodiester backbone is represented as -O-P-O-CH2-] of US 5,489,677, and the amide backbones of US 5,602,240.

The antisense compounds useful in the methods of the present disclosure also include oligonucleotides having morpholino backbone structures ofUS 506.

Modified sugars Antisense compounds useful in the methods of the present disclosure include ucleotides having one or more tuted sugar moieties.

Examples include oligonucleotides complising one of the following at the 2' position: OH; F; 0-, S-, or N-alkyl; O-, S-, or N-alkenyl; 0-, S- or N-alkynyl; or O- alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or tituted C1 to C10 alkyl or C2 to C10 alkenyl and alkynyl.

In one embodiment, the oligonucleotide comprises one of the following at the 2' position: O[(CH2)nO]mCH3, O(CH2)nOCH3, O(CH2)nNH2, O(CH2)nCH3, O(CH2)nONH2, and nON[(CH2)nCH3]2, where n and m are from 1 to about 10.

Further examples include of modified oligonucleotides e oligonucleotides 3O sing one of the following at the 2' position: C1 to C10 lower alkyl, substituted lower alkyl, alkenyl, alkynyl, l, aralkyl, O-alkaryl or O-aralkyl, SH, SCH3, OCN, Cl, Br, CN, CF3, OCF3, SOCH3, SOzCH3, ONOZ, N02, N3, NHZ, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharrnacokinetic properties of an oligonucleotide, or a group for improving the pharrnacodynamic properties of an oligonucleotide, and other substituents having similar properties.

In one embodiment, the modification includes 2'—methoxyethoxy (2'-O- CH2CH20CH3 (also known as 2'-O-(2-methoxyethyl) or 2'-MOE) (Martin et al., 1995), that is, an alkoxyalkoxy group. In a further embodiment, the ation includes 2'- dimethylaminooxyethoxy, that is, a 2ON(CH3)2 group (also known as 2'- DMAOE), or 2'—dimethylaminoethoxyethoxy (also known in the art as 2'—O-dimethyl- amino-ethoxy-ethyl or 2'-DMAEOE), that is, 2'-O-CH2-O-CH2-N(CH3)2.

Other modifications include 2'—methoxy (2'—O-CH3), 2'—aminopropoxy (2'- OCH2CH2CH2NH2), 2'-allyl (2'-CH2-CH=CH2), 2’-O-allyl (2'—O-CH2-CH=CH2) and 2'- fluoro (2'-F). The 2'-modification may be in the arabino (up) on or ribo (down) position. In one embodiment a 2'-arabino modification is 2'-F.

Similar modifications may also be made at other positions on the oligonucleotide, particularly the 3’ position of the sugar on the 3' terminal nucleotide or in 2'—5' linked oligonucleotides and the 5' position of the 5' terminal nucleotide.

Oligonucleotides may also have sugar mimetics, such as cyclobutyl moieties in place of the pentofuranosyl sugar. entative United States s that teach the ation of such modified sugar structures include, but are not limited to, US 4,981,957, US 5,118,800, US 5,319,080, US 5,359,044, US 5,393,878, US 137, US 5,466,786, US 5,514,785, US 134, US 5,567,811, US 5,576,427, US 5,591,722, US 5,597,909, US ,610,300, US 5,627,053, US 5,639,873, US 5,646,265, US 5,658,873, US 5,670,633, US 5,792,747, and US 5,700,920.

A r modification of the sugar includes Locked c Acids (LNAs) in which the 2'-hydroxyl group is linked to the 3' or 4' carbon atom of the sugar ring, thereby g a bicyclic sugar moiety. In one embodiment, the linkage is a methylene (-CH2-)n group bridging the 2' oxygen atom and the 4' carbon atom, wherein n is 1 or 2. LNAs and preparation thereof are described in WO 98/39352 and W0 99/14226.

Natural and modified nucleobases Antisense compounds useful in the methods of the present disclosure include oligonucleotides having nucleobase modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases e (T), cytosine (C) and uracil (U).

Modified nucleobases include other synthetic and natural nucleobases such as, for e, 5-methylcytosine C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2- thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl (-CEC-CH3) uracil and cytosine and other alkynyl tives of pyrimidine bases, 6-azo uracil, cytosine and thymine, 5-uracil ouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8- thioalkyl, oxyl and other 8-substituted adenines and guanines, 5-halo particularly -bromo, 5-trifluoromethyl and other tituted uracils and cytosines, 7- methylguanine and 7-methyladenine, 2-F-adenine, 2-amino—adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3- deazaadenine.

Further modified nucleobases include tricyclic pyrimidines, such as phenoxazine cytidine(1H-pyrimido[5,4-b][1,4]benzoxazin-2(3H)-one), phenothiazine cytidine (1H- pyrimido[5,4-b][1,4]benzothiazin-2(3H)—one), G—clamps such as, for example, a substituted phenoxazine cytidine (e.g., 9-(2-aminoethoxy)-H-pyrimido[5,4- b][l,4]benzoxazin-2(3H)-one), carbazole cytidine (2H-pyrimido[4,5-b]indolone), pyridoindole cytidine (H-pyrido[3',2’:4,5]pyrrolo[2,3-d]py1imidinone).

Modified nucleobases may also include those in which the purine or pyrimidine base is ed with other heterocycles, for example, 7-deaza-adenine, 7- deazaguanosine, opyridine and 2-pyridone. Further nucleobases e those disclosed in US 3,687,808, those disclosed in J .I. Kroschwitz (editor), The Concise Encyclopedia of Polymer Science and ering, pages 858-859, John Wiley and Sons (1990), those disclosed by Englisch et al. (1991), and those disclosed by Y.S.

Sanghvi, Chapter 15: Antisense Research and Applications, pages 289-302, S.T.

, B. Lebleu (editors), CRC Press, 1993.

Certain of these nucleobases are ularly useful for increasing the g affinity of the oligonucleotide. These include tituted pyrimidines, 6- azapyrimidines and N—2, N—6 and 0-6 substituted s, ing 2- 3O aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2 °C.

In one embodiment, these nucleobase substitutions are combined with 2'—O- methoxyethyl sugar modifications.

Representative United States patents that teach the preparation of certain of the above noted modified nucleobases as well as other d nucleobases include, but are not limited to, US 3,687,808, US 4,845,205, US 5,130,302, US 5,134,066, US ,175,273, US 5,367,066, US 5,432,272, US 5,457,187, US 5,459,255, US 5,484,908, US 5,502,177, US 5,525,711, US 5,552,540, US 5,587,469, US 5,594,121, US ,596,091, US 5,614,617, US 985, US 5,830,653, US 5,763,588, US 6,005,096, US 5,681,941 and US 5,750,692.

Conjugates Antisense compounds useful in the s of the present disclosure may be conjugated to one or more moieties or groups which enhance the activity, cellular distribution or cellular uptake of the antisense compound.

These moieties or groups may be covalently bound to functional groups such as primary or secondary hydroxyl groups.

Exemplary moieties or groups include intercalators, reporter molecules, polyamines, polyamides, polyethylene glycols, polyethers, groups that enhance the pharmacodynamic properties of oligomers, and groups that enhance the pharmacokinetic properties of oligomers. Typical conjugate groups include terols, lipids, phospholipids, biotin, phenazine, folate, phenanthridine, anthraquinone, acridine, ceins, rhodamines, coumarins and dyes.

Moieties or groups that enhance the pharmacodynamic properties include those that improve uptake, enhance resistance to degradation, and/or then ce- specific hybridization with the target nucleic acid.

Moieties or groups that enhance the pharmacokinetic properties include those that improve uptake, bution, metabolism or excretion of the nse nds.

Representative moieties or groups are disclosed in 92/O9l96 and US 6,287,860.

Moieties or groups include but are not limited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, for example, hexyl-S-tritylthiol, a thiocholesterol, an tic chain, for example, dodecandiol or undecyl residues, a phospholipid, for example, di—hexadecyl-rac—glycerol or triethylammonium 1,2-di—O- hexadecyl-rac—glyceroH-phosphonate, a polyamine or a polyethylene glycol chain, 3O or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino- carbonyl-oxycholesterol moiety.

Antisense compounds useful in the methods of the present disclosure may also be conjugated to active drug substances. This includes the Somatostatin t, for example, tide, Lanreotide or Pasireotide. Techniques to ate to Octreotide are known to those skilled in the art. ucleotide-drug conjugates and their preparation are described in US 09/334,130.

Representative United States patents that teach the preparation of such conjugates include, but are not d to, US 4,828,979, US 4,948,882, US 5,218,105, US 5,525,465, US 5,541,313, US 5,545,730, US 5,552,538, US 5,578,717, US ,580,731, Ls 5,580,731, US 5,591,584, US 5,109,124, US 5,118,802, Ls 045 7 US 5,414,077, US 5,486,603, US 5,512,439, US 5,578,718, US 5,608,046, US 4,587,044, Ls 4,605,735, US 4,667,025, US 4,762,779, US 4,789,737, Ls 941 7 US 4,835,263, US 335, US 4,904,582, US 4,958,013, US 5,082,830, US 5,112,963, Ls 5,214,136, US 830, US 5,112,963, US 5,214,136, Ls 5,245,0227 US 5,254,469, US 5,258,506, US 5,262,536, US 250, US 5,292,873, US ,317,098, Ls 5,371,241, US 5,391,723, US 5,416,203, US 5,451,463, Ls 5,510,475 7 US 5,512,667, US 5,514,785, US 5,565,552, US 5,567,810, US 5,574,142, US ,585,481, Ls 371, US 5,595,726, US 5,597,696, US 5,599,923, US 5,599,928 and US 5,688,941.

Chimeric compounds As would be appreciated by those skilled in the art, it is not necessary for all positions in a given compound to be uniformly modified and in fact, more than one of the entioned modifications may be incorporated in a single oligonucleotide or even at a single nucleoside within an oligonucleotide.

Antisense compounds useful in the methods of the present disclosure e chimeric oligonucleotides. ric oligonucleotides" contain two or more chemically distinct regions, each made up of at least one monomer unit, that is, a tide in the case of an oligonucleotide compound. These oligonucleotides typically contain at least one region wherein the oligonucleotide is modified so as to confer upon the oligonucleotide increased resistance to nuclease degradation, increased cellular uptake, increased stability and/or increased binding affinity for the target nucleic acid. An additional region of the oligonucleotide may serve as a ate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of e, RNAse H is a cellular endonuclease which cleaves the RNA strand of an RNAzDNA duplex. Activation of RNase H, therefore, results in cleavage of the RNA , thereby greatly enhancing the efficiency of oligonucleotide—mediated inhibition of gene expression, The cleavage of RNA:RNA hybrids can, in like fashion, be accomplished through the actions of endoribonucleases, such as RNAseL which cleaves both cellular and viral RNA. Cleavage of the RNA target can be routinely detected by gel electrophoresis and if necessary, associated nucleic acid hybridization techniques known in the art.

Chimeric antisense compounds useful in the methods of the present disclosure may be formed as composite structures of two or more oligonucleotides, modified oligonucleotides, and/or oligonucleotide mimetics. Such nds have also been referred to in the art as hybrids or gapmers.

Representative United States patents that teach the preparation of such hybrid structures include, but are not limited to, US 830, US 5,149,797, US 5,220,007, US 5,256,775, US 5,366,878, US 5,403,711, US 5,491,133, US 5,565,350, US 5,623,065, US 355, US 5,652,356, and Us 922.

Exemplary oligonucleotides In one embodiment, the nse compound is a second generation phosphorothioate backbone 2'-MOE-modif1ed chimeric oligonucleotide gapmer designed to hybridize to GHR mRNA. ary oligonucleotides are shown in Table 1. "Target site" indicates the first (5'—most) nucleotide number on the particular target sequence to which the ucleotide binds. "% Inhib" indicates the inhibitory effect on hGI-IR mRNA levels by quantitative real-time PCR. Data are averages from three experiments in which MCF7 cells were treated with the nse oligonucleotides.

Table 1: Inhibition of human growth hormone receptor mRNA levels by chimeric phosphorothioate oligonucleotides having 2'-MOE wings and a deoxy gap ISIS # REGION TARGET TARGET SEQUENCE % SEQ SEQ ID SITE INHIB ID NO ——————-a ——————n 227488 8884 ———n:3 LQ 227488 888488 227478 888488 ———m 227488 888488 ———m 227484 888488 227482 888488 227488 888488 227484 OOQ. ,_._ 88 227488 888488 _——m 227488 888488 227488 888488 227488 878448 ISIS # REGION TARGET TARGET SEQUENCE % SEQ SEQ ID SITE INHIB ID NO 4043 catagcagcaaagtagcaga E- 4183 gctatttttggctatagaaa 4197 gattgaggtatttagctatt ---272302 Start 4 --—272303 Start 36 ccagagatccatacctgtag 25 LO 115 :gctaaggatagctgctgtg 8 LO 160 Fr Fr LO Fr O Fr Fr Ff SD C: LO O 0 Fr LOQ SD (‘T (‘f SD E- NN \lm Codi,_> LQ 170 :tagaagaatttgtctttag 28 > LQLQ 185 \QLQ tgaatttaggc:ccttaga 274 gggtcO Fr SDQkQ (‘T (‘f 0 Codi,_> LQ 362 :aacagctgttt :ccccagc Codi,_> LQLQLQ 439 :ttcatccactg:accacca 468 tgcactatttcatcaacag 480 gggtggatctgg tooaota COdi’l LO 564 SD Fr Fr LO 0 LQ Fr LQ LQ H“ LO 0 toooato 652 ccatca :tttcca 684 caatgagtacac tg 1 752 aactcgccataa :ttccaga 857 agcccaaatattccaaaga 272318— 272319— 272320 Codi _ 272321 Codi aacccaagagtcatcactgt 272322 Codi #55 272323 Codin 272324 Codi5LQKQLQLQKQ 272325 OOQ. '_l ,_> LQ _—-m 272326 Codi {3 LQLQ 272327 Codi :3 —-—m 272328 OOQ. '_l ,_> LQ 272329!Codin 272330 CodinLQ 272331 Codi,_> LQ 272332 Codi,_> LQ 272333!Codin 272334 Stop Cocoa 272335 (/0 VLF_| SC! 272336 w U ———m 272337 w L 272338 w L I31] WNN ———m 272339 l UM ,u 272340 0000 L r_‘ ,u _——m 272341i1 L r1R 3'Ur-I 3I‘Lr'l /U/U ——-§-m _——m ———m ISIS # REGION TARGET TARGET SEQUENCE % SEQ SEQ ID SITE INHIB ID NO —————n- 272355 intron: 5 6418 ttgagtgttcctaaaatgaa 24 77 exon junction 272357 : 5 22712 tagggtccatctttcaagac 62 79 exon junction ——————m 272360 exon: 5 29935 tattagttaccttgaggaga 82 intron junction 272361 intron: 5 30267 attttccttcctagaaaata 10 83 exon junction All oligonucelotides in Table l are chimeric oligonucleotides ("gapmers"), 20 nucleotides in length, composed of a central 'gap" region consisting of ten 2'- deoxynucleotides, which is flanked on both sides (5’ and 3’ directions) by five- nucleotide "wings". The wings are ed of 2'-methoxyethyl E) nucleotides. The internucleoside (backbone) linkages are phosphorothioate (P=S) throughout the oligonucleotide. All uracils are 5-methyluracils (MeU). Typically, the ucleotide is synthesized using 2—methoxyethyl modified thymidines not 5- methyluracils. All pyrimidines are C5 methylated (i.e., U, T, C are C5 methylated).

The oligonucleotide may be synthesized by a multi-step process that may be divided into two distinct operations: solid-phase synthesis and downstream sing.

In the first operation, the nucleotide sequence of the oligonucleotide is assembled through a computer-controlled solid-phase sizer. Subsequent downstream processing includes deprotection steps, preparative reversed-phase chromatographic ation, isolation and drying to yield the oligonucleotide drug substance. The chemical synthesis of the oligonucelotide utilizes phosphoramidite coupling chemistry ed by oxidative sulfurization and involves sequential coupling of activated monomers to an elongating oligomer, the 3’—terminus of which is covalently attached to the solid support.

Delritylalion (reaction a).

Each cycle of the solid-phase synthesis commences with removal of the acid- labile 5'-O-4, 4'—dimethoxytrityl (DMT) protecting group of the 5' terminal nucleoside of the support bound oligonucleotide. This is accomplished by treatment with an acid on (e.g,, dichloroacetic acid (DCA) in toluene). Following detritylation, excess reagent is removed from the support by washing with acetonitrile in preparation for the next reaction.

Coupling (reaction 1)) Chain elongation is ed by reaction of the 5'-hydroxyl group of the support-bound oligonucleotide with a solution of the phosphoramidite corresponding to that particular base position (e.g., for base2: MOE-MeC amidite) in the presence of an activator (e.g., lH-tetrazole). This results in the formation of a phosphite triester linkage between the incoming nucleotide synthon and the support-bound oligonucleotide chain. After the coupling reaction, excess reagent is removed from the support by washing with acetonitrile in preparation for the next reaction. izalion (reaction 0) The newly formed phosphite triester e is converted to the corresponding [0, O, O)-trialkyl phosphorothioate triester by treatment with a solution of a sulfur transfer t (e.g., phenylacetyl lde). Following sulfurization, excess reagent is removed from the support by washing with acetonitrile in preparation for the next reaction.

Capping (reaction a9 A small proportion of the 5'-hydroxy groups available in any given cycle fail to . Coupling of these groups in any of the subsequent cycles would result in formation of process—related impurities ("DMT-on (n-l)-mers") which are difficult to separate from the desired t. To prevent ion of these impurities and to 3O facilitate purification, a "capping t" (e.g., acetic anhydride and N- methylimidazole/acetonitrile/pyridine) is introduced into the reactor vessel to give capped ces. The resulting failure sequences ("DMT-off ers") are separated from the d product by reversed phase HPLC purification. After the capping reaction, excess reagent is removed from the support by washing with acetonitrile in preparation of the next reaction.

Reiteration of this basic four-step cycle using the appropriate protected nucleoside phosphoramidite allows assembly of the entire protected oligonucleotide Sequence.

Backbone deprotection (reaction e) Following tion of the assembly portion of the process the cyanoethyl groups ting the (O, O, O)—trialkyl phosphorothioate triester cleotide linkages are removed by treatment with a solution of triethylamine (TEA) in acetonitrile. The reagent and acrylonitrile generated during this step are removed by washing the column with itrile.

Cleavageflom support and base deprotection (reactionfl Deprotection of the exocyclic amino groups and cleavage of the crude product from the support is achieved by incubation with aqueous um hydroxide (reaction f). Purification of the crude, 5'-O-DMT-protected product is accomplished by reversed phase HPLC. The reversed phase HPLC step removes DMT-off failure sequences. The elution profile is monitored by UV tion spectroscopy. Fractions containing DMT-on oligonucleotide product are collected and ed.

Acidic deprotection (reaction g) Reversed phase HPLC fractions containing 5'-O-DMT-protected ucleotide are pooled and transferred to a precipitation tank. The products obtained from the purification of several syntheses are combined at this stage of the process. Purified DMT—on oligonucleotide is treated with acid (e.g., acetic acid) to remove the DMT group attached to the 5' terminus. After acid exposure for the prescribed time and neutralization, the oligonucleotide drug substance is isolated and dried.

Following the final acidic deprotection step, the on is neutralized by on of aqueous sodium ide and the oligonucleotide drug nce is precipitated from solution by adding ethanol. The precipitated material is allowed to settle at the bottom of the reaction vessel and the ethanolic supernatant decanted. The precipitated material is olved in purified water and the solution pH adjusted to between pH 7.2 and 7.3. The precipitation step is repeated. The precipitated material is dissolved in water and the on filtered through a 0.45 micron filter and transferred into disposable polypropylene trays that are then loaded into a lyophilizer.

The solution is cooled to -50°C. Primary drying is carried out at 25°C for 37 hours.

The temperature is increased to 300°C and a secondary drying step performed for 5.5 hours. ing completion of the lyophilization process, the drug substance is transferred to high density polyethylene bottles and stored at -200°C.

Target nucleic acid "Targeting" an antisense compound to a particular nucleic acid can be a multistep process. The process usually begins with the identification of a target nucleic acid whose function is to be modulated. In the present sure, the target nucleic acid encodes growth hormone receptor (GI-IR). The term "target nucleic acid" encompasses DNA encoding GHR, RNA (including pre-mRNA and mRNA or portions thereof) transcribed from such DNA, and further, cDNA derived from such RNA.

The cDNA encoding the growth hormone receptor has been cloned from many species. The receptor consists of an extracellular e-binding region (exons 2—7), a single membrane spanning region (exon 8), and an intracellular region (exons 9—10).

There are also le alternative 5' untranslated regions which are alternative first exons of the gene, in both the human and mouse ripts. Growth hormone receptor has no intrinsic kinase domain, but the intracellular region plays a major role in the signal transduction process. A truncated form of the receptor, known as growth hormone binding protein , lacks the transmembrane and intracellular regions of GHR and is secreted into the serum. The truncated n is produced by one of two different processes, depending on the animal species. In mice and rats, alternative splicing of GHR precursor messenger RNA replaces the transmembrane and intracellular regions with a very short hydrophilic tail (encoded by exon 8A). In humans, cows, and pigs (among ), no alternative RNA splicing is apparent but instead the GHBP is produced by proteolysis of the GHR. The GHBP appears to be to modulate the level of circulating growth hormone (GH).

In one embodiment the GHR is a human GHR (hGHR) having a nucleotide ce as shown in NM_000163.4 (SEQ ID N04) or NG_011688 (4852-302955) (SEQ ID NO:5).

The targeting s usually also es ination of at least one target 3O region, segment, or site within the target nucleic acid for the antisense interaction to occur such that the desired effect, for example, inhibition of expression, will result.

The term "region" as used herein is defined as a portion of the target nucleic acid having at least one identifiable structure, function, or characteristic. Within s of the target nucleic acids are segments. "Segments" are defined as smaller or sub- portions of regions within a target nucleic acid. " as used herein, means positions within the target nucleic acid.

Since the "translation initiation codon" is typically 5'-AUG (in transcribed mRNA molecules; 5'-ATG in the ponding DNA molecule), the ation initiation codon is also referred to as the "AUG codon", the "start codon" or the "AUG start codon". A minority of genes have a translation initiation codon having the RNA sequence 5'-GUG, , or 5'-CUG, and 5'-AUA, 5'-ACG and 5'-CUG have been shown to function in vivo. Thus, the terms "translation initiation codon" and "start codon" can encompass many codon sequences even though the initiator amino acid in each instance is typically methionine (in eukaryotes) or formylmethionine (in prokaryotes). It is also known in the art that eukaryotic and prokaryotic genes may have two or more alternative start codons, any one of which may be preferentially ed for translation initiation in a particular cell type or tissue, or under a particular set of ions. The terms "start codon" and "translation initiation codon" as used herein refer to the codon or codons that are used in vivo to initiate translation of an mRNA transcribed from a gene encoding, for e, GHR, regardless of the sequence(s) of such codons.

A "translation termination codon" also referred to as a "stop codon" may have one of three RNA ces: 5'-UAA, 5'-UAG and 5'-UGA (5'-TAA, 5'-TAG and 5'- TGA, respectively in the corresponding DNA molecule). The terms "translation termination codon" and "stop codon" as used herein refer to the codon or codons that are used in vivo to terminate translation of an mRNA transcribed from a gene encoding the GHR, regardless of the ce(s) of such codons.

The terms "start codon region" and "translation initiation codon " refer to a portion of the mRNA or gene that encompasses from about 25 to about 50 uous nucleotides in either direction (i.e., 5' or 3') from the translation initiation codon.

Similarly, the terms and "stop codon region" and "translation termination codon region" refer to a portion of the mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from the translation termination codon. Consequently, the "start codon " or "translation initiation codon region" and the "stop codon region" or "translation termination codon region" are all regions 3O which may be targeted effectively with the antisense compounds.

The "open reading frame" (ORF) or g region", which is known in the art to refer to the region between the translation initiation codon and the translation termination codon, is also a region which may be targeted effectively. In one embodiment, the intragenic region encompassing the translation initiation or termination codon of the ORF of a gene is targeted.

Other target regions include the 5' untranslated region (5'UTR), known in the art to refer to the portion of the mRNA in the 5' direction from the translation tion codon, and thus including tides between the 5' cap site and the translation initiation codon of the mRNA (or corresponding nucleotides on the gene), and the 3' untranslated region (3 'UTR), known in the art to refer to the portion of the mRNA in the 3' direction from the translation termination codon, and thus including nucleotides between the ation termination codon and 3' end of the mRNA (or corresponding nucleotides on the gene). The 5’ cap site of an mRNA comprises an N7-methylated guanosine residue joined to the 5'-most residue of the mRNA via a 5'-5' triphosphate linkage. The 5' cap region of an mRNA is ered to include the 5’ cap structure itself, as well as the first 50 nucleotides adjacent to the cap site. In one ment, the 5’ cap region is targeted.

Although some eukaryotic mRNA transcripts are directly translated, many contain one or more regions, known as "introns,” which are excised from a transcript before it is translated. The remaining (and therefore translated) regions are known as "exons" and are d together to form a continuous mRNA sequence. mRNA transcripts ed via the process of ng of two (or more) mRNAs from different gene sources are known as "fusion transcripts". In one embodiment, introns, or splice sites, that is, intron-exon junctions or exon-intron junctions, or aberrant fusion junctions due to rearrangements or deletions are targeted.

Alternative RNA transcripts can be produced from the same genomic region of DNA. These alternative transcripts are generally known as "variants".

"Pre-mRNA variants" are transcripts produced from the same genomic DNA that differ from other transcripts produced from the same genomic DNA in either their start or stop position and contain both ic and exonic sequence. Upon excision of one or more exon or intron regions, or portions thereof during splicing, pre-mRNA variants e r "mRNA variants". Consequently, mRNA variants are processed pre—mRNA variants and each unique pre-mRNA variant must always produce a unique mRNA variant as a result of splicing. These mRNA variants are also known as native splice variants". If no splicing of the pre-mRNA variant occurs then the pre-mRNA variant is identical to the mRNA variant.

In mouse, rat and monkey, GHBP, which is the soluble shortened form of GHR, is produced by alternative splicing of the GHR primary transcript. In some embodiments it may be preferable to target regions of the transcript which are present in both the GHR transcript and in the shorter GHBP transcript. In other embodiments it may be preferable to target regions of the mRNA which are only present in the longer 2014/000613 GHR transcript. In humans, cows, and pigs (among others), no alternative RNA splicing is apparent but instead the shorter GHBP is produced by proteolysis of the GHR. It will be tood that in the context of this disclosure, "nucleic acid encoding G " includes nucleic acid encoding GHBP.

Variants can be produced through the use of alternative signals to start or stop transcription, that is, through use of an alternative start codon or stop codon. Variants that originate from a NA or mRNA that use alternative start codons are known as "alternative start variants" of that pre-mRNA or mRNA. Those transcripts that use an alternative stop codon are known as "alternative stop variants" of that pre—mRNA or mRNA. One specific type of alternative stop variant is the "polyA variant” in which the multiple transcripts produced result from the alternative selection of one of the "polyA stop signals" by the transcription machinery, thereby producing transcripts that terminate at unique polyA sites. In one embodiment, the pre—mRNA or mRNA variants are targeted. The human GHR has several transcript variants as can be identified from the National Center for Biotechnology Information http://wwwncbi.nlm.nih.gov/guide/ and other web sites http://Www.uniprot.org/uniprot/P10912#PRO_0000010958. There are additionally alternative sequences and natural variants sequences of these transcripts.

The location on the target nucleic acid to which the antisense compound hybridizes is ed to as the "target segment". As used herein, the term "target t" is defined as at least an eobase portion of a target region to which an antisense compound is targeted. While not g to be bound by theory, it is tly believed that these target ts represent portions of the target nucleic acid which are accessible for hybridization.

Once one or more target regions, segments or sites have been identified, antisense compounds are chosen which are sufficiently complementary to a target t, that is, antisense compounds that hybridize sufficiently well and with ent specificity, to give the desired effect.

In a further embodiment, the target segment identified herein may be employed 3O in a screen for additional compounds that modulate the expression of the GHR gene (and thus expression of GHR). "Modulators" are those compounds that decrease or increase the expression of a nucleic acid molecule ng GHR and which comprise at least a 8 nucleobase portion which is complementary to a preferred target segment.

The screening method comprises the steps of contacting a target segment of the nucleic acid encoding GHR with one or more candidate modulators, and selecting for one or more candidate modulators which decrease or se the expression of a nucleic acid encoding GHR. Once it is shown that the candidate modulator or modulators are capable of modulating (e.g., either decreasing or sing) the expression of a nucleic acid encoding GHR, the modulator may then be employed in further igative s of the function of GHR, or for use as a research, diagnostic, or therapeutic agent.

The target segment may also be ed with its respective complementary antisense compound to form stabilized double-stranded (duplexed) oligonucleotides.

Such double stranded ucleotide moieties have been shown in the art to modulate target expression and regulate translation, as well as RNA processing via an antisense mechanism. Moreover, the double-stranded moieties may be subject to chemical modifications (Fire et al., 1998; Timmons and Fire, 1998; s et al., 2001; Tabara et al., 1998; Montgomery et al., 1998; Tuschl et al., 1999; Elbashir et al., 2001a; Elbashir et al., 2001b). For example, such double-stranded moieties have been shown to inhibit the target by the classical hybridization of antisense strand of the duplex to the target, thereby triggering enzymatic degradation of the target (Tijsterman et al., 2002).

Exemplary target nucleic acids Exemplary target sequences are shown in Table 2.

Table 2: Sequence and on of preferred target segments identified in growth hormone receptor SITE TARGET TARGET SEQUENCE REV COMP ACTIVE IN SEQ ID SEQoID SITE OF SEQ ID NO _l°-— aaagaatgccctga 2.44071—“37—gaaagaatgccctgattatg ———ccagttccaaagattaaagg _n—attgagctagatattgatga ..44os7n— gacacagacagacttctaag ———agcgacattacaccagcagg——m "l-aaccaagaggacatttacat“- -44oeen— agaggacatttacatcacca tttacatcaccacagaa _l-_ tacatcaccacagaaagcct -44102—— caccacagaaagccttacca —_-z- gtgagcacagaccaact——— _l-_ gagcacagaccaactgaacam 441081-—ccaactgaacaaaatcatgc—__ ——4043 tctgctactttgctgctatg—m- _I-4183 tttctatagccaaaaatagc—m 4197 aatagctaaatacctcaatc—__ WO 97938 SITE TARGET TARGET SEQUENCE REV COMP ACTIVE IN SEQ ID ID SEQ ID SITE OF SEQ ID NO __———_- 1—03 ——04 mu--05 __———l- —. O \1 __———- "—n—m __———l-— .. __———l-— .. __———-— .. |_\ \I n”_ H. sapiens “053 acagtgatgactcttgggt H. sapiens I‘I _nI O (I) ID- gctagatattgatgagccaLQ H. sapiens I _nI I—‘ I—‘ O agactgaggaatcagacaca H. sapiens 2.236 atttcaatgccaatgacata UTLTIUIUWQTI kOOO\IO\U'| H. sapiens I‘I _nI 00 O N aagcagatctcttatgcctt H. sapiens I _nI lb N O tcctactgaaggagctgagt H. sapiens 2.560 agaataaggcagggatgtcc Ch H. sapiens I‘I _nI ON N 00 acttccttatggacaatgcc ON H. sapiens I _nI 0 01 I—‘ tgaggcagatgccaaaaagt H. sapiens 2.656 cagatgccaaaaagtgcatc H. sapiens I‘I I 03 O‘\ I—‘ cctcatactcaatgcgactLO H. sapiens I _nI CI) (I) ID- tgcccttgcctgacaaagaLO 0 \I H. sapiens 2.913 ggctatgtgagcac H. sapiens I‘I 0000NNNNNNNNNNI—‘I—I I—‘OkOCOQGWerNI—‘OKOOD I k0 ID- 0 ccttagcctttct H. sapiens I 00 N _nI 0 \I 00 agagctacgtattt \I O H. sapiens ctgtttagtagcagtgatt 71 H. sapiens \I 00 H. sapiens _n———H. sapiens . _————l-......I‘I 00000000000000 KOQ)\IO\U‘IIJ>00 —————m_ --41 .. .b. N —————n_43 __44 mu--45 —————m__47 mu-. .b (I) __———l- . ..

S ITE TARGET TARGET SEQUENCE REV COMP ACTIVE IN SEQ ID ID SEQ ID SITE OF SEQ ID NO 188574_ 25543 gtttagattctatctggaga 188575_ 29755 aaagtaccagaatatttgga Compositions/Formulations nse compounds useful in the s of the present disclosure may be admixed, encapsulated, conjugated or otherwise associated with other molecules, le structures or mixtures of compounds, resulting in, for example, liposomes, receptor-targeted molecules, oral, rectal, l or other formulations, for assisting in uptake, distribution and/or absorption.

Representative United States patents that teach the preparation of such uptake, distribution and/or absorption-assisting formulations include, but are not limited to, US 5,108,921, US 5,354,844, US 5,416,016, US 5,459,127, US 5,521,291, US 5,543,158, Us 5,547,932, US 5,583,020, US 5,591,721, US 4,426,330, US 4,534,899, US ,013,556, US 921, US 5,213,804, US 5,227,170, US 221, US 633, Us 5,395,619, US 5,416,016, US 5,417,978, US 5,462,854, US 5,469,854, Us ,512,295, US 5,527,528, US 5,534,259, US 152, US 948, US 5,580,575, and US 5,595,756.

The antisense compounds may be administered in a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" refers to molecular entities that do not produce an allergic, toxic or otherwise adverse reaction when administered to a subject, particularly a mammal, and more particularly a human. The ceutically acceptable carrier may be solid or liquid. Useful examples of ceutically acceptable carriers include, but are not limited to, diluents, solvents, surfactants, ents, suspending agents, buffering agents, lubricating agents, adjuvants, vehicles, emulsifiers, absorbants, dispersion media, coatings, stabilizers, protective colloids, adhesives, thickeners, thixotropic agents, penetration agents, sequestering agents, isotonic and absorption delaying agents that do not affect the activity of the active agents of the disclosure.

The antisense compounds may be pharmaceutically acceptable salts, esters, or salts of the , or any other nds which, upon administration are capable of providing (directly or indirectly) the biologically active metabolite. 3O The term "pharmaceutically acceptable salts" as used herein refers to physiologically and pharmaceutically acceptable salts of the nse compounds that retain the desired biological ties of the parent compounds and do not impart undesired logical effects upon administration. red examples of pharmaceutically acceptable salts and their uses are further described in US 6,287,860.

The antisense compounds may be gs or pharmaceutically able salts of the prodrugs, or other bioequivalents.

The term "prodrugs" as used herein refers to therapeutic agents that are prepared in an inactive form that is converted to an active form (i.e., drug) upon administration by the action of endogenous enzymes or other chemicals and/or conditions. In particular, prodrug forms of the antisense compounds are prepared as SATE [(S acetyl- 2-thioethyl) phosphate] derivatives according to the methods disclosed in WO 93/24510, WO 94/26764 and US 5,770,713.

Somatostatin agonsits may be administered in a pharmaceutically acceptable r. The carrier must be "acceptable" in the sense of being compatible with the active ingredient(s) of the ation (e.g., capable of stabilizing peptides) and not deleterious to the t to be treated. bly, the ation should not include oxidizing agents or other substances with which peptides are known to be incompatible.

For example, somatostatin agonists in the cyclized form (e.g., internal cysteine disulfide bond) are oxidized; thus, the presence of reducing agents as excipients could lead to an opening of the cysteine disulfide bridge. On the other hand, highly oxidative conditions can lead to the formation of cysteine sulfoxide and to the oxidation of tryptophane. Consequently, it is important to carefully select the excipient. pH is another key factor, and it may be necessary to buffer the product under slightly acidic conditions (pH 5 to 6).

The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient(s) into ation with the carrier which constitutes one or more accessory ingredients.

In general, the formulations for tablets or powders are prepared by uniformly and intimately blending the active ingredient with finely divided solid carriers, and then, if necessary, as in the case of tablets, forming the product into the desired shape 3O and size.

Formulations le for parenteral (e.g., intravenous) administration, on the other hand, conveniently comprise sterile aqueous solutions of the active ingredient(s).

Preferably, the solutions are isotonic with the blood of the subject to be treated. Such formulations may be conveniently ed by ving active ingredient(s) in a solvent comprising water to e an aqueous solution, and rendering said solution sterile. The formulation may be ted in unit or dose containers, for example, sealed ampoules or vials.

Formulations suitable for sustained release parenteral administrations (e.g., biodegradable polymer ations) are also well known in the art (see, for example, US. Pat. Nos. 3,773,919 and 4,767,628 and PCT Publication No. WO 94/15587). itions for rectal or vaginal administration are preferably suppositories which may contain, in addition to the active substance, excipients such as coca butter or a suppository wax. itions for nasal or sublingual administration are also prepared with standard ents well known in the art.

For topical administration, they are best used in the form of solutions, creams, , lotions, ointments and the like.

Administration The methods of the present disclosure rely on the unsuspected additional activity and/or synergy of combining a statin analog having Somatostatin receptor agonistic activity with an oligonucleotide targeted to growth hormone receptor (GHR) to reduce insulin-like growth factor I (IGF-I) levels in a subject.

In a particular embodiment of the present disclosure, the Somatostatin agonist the oligonucleotide are administered concomitantly. The statin agonist and the oligonucleotide may be administered in the form of a composition comprising an admixture of both components. Alternatively, the Somatostatin agonist and the ucleotide may be administered in separate compositions.

In one embodiment, the antisense oligonucelotide is administered systemically.

As used herein "systemic administration" is a route of administration that is either enteral or parenteral.

As used herein "enteral" refers to any form of administration that involves any part of the gastrointestinal tract and includes oral administration of, for example, the antisense oligonucleotide in tablet, capsule or drop form; gastric feeding tube, duodenal 3O feeding tube, or gastrostomy; and rectal stration of, for example, the antisense compound in suppository or enema form.

As used herein teral" includes administration by injection or infusion.

Examples include, intravenous (into a vein), rterial (into an artery), intramuscular (into a muscle), intracardiac (into the heart), subcutaneous (under the skin), intraosseous infusion (into the bone marrow), intradermal, (into the skin itself), intrathecal (into the spinal canal), intraperitoneal (infusion or injection into the peritoneum), intravesical (infusion into the urinary bladder), transdermal (diffusion h the intact skin), transmucosal (diffusion through a mucous membrane), inhalational.

The antisense ucleotide may be administered as single dose or as repeated doses on a periodic basis, for example, daily, once every two days, three, four, five, six seven, eight, nine, ten, eleven, twelve, thirteen or fourteen days, once weekly, twice weekly, three times weekly, or every two weeks, every three weeks, or every four weeks.

The antisense oligonucleotide to be used in the therapy is ated and closed in a fashion consistent with good medical practice, taking into account the specific condition being treated, the clinical condition of the individual patient, the site of delivery of the oligonucleotide, the method of administration, the scheduling of administration, and other s known to practitioners. The "effective amount" of oligonucelotide for purposes herein is thus determined by such considerations. The term "effective amount" in this context refers to any dose of the antisense oligonucleotide sufficient to inhibit GHR expression, under the conditions of administration.

By way of example, a dose of 0 mg, more preferably 50-1600 mg oligonucelotide may be administered to a subject over a week. A single dose of 150- 400 mg, for example, a dose of 250 mg is particularly contemplated for humans. In one embodiment, a dose of 250 mg per day is administered six times over 3 weeks, on days 1, 3, 5, 7, l4 and 21 or twice . In another embodiment, a dose of 250 mg is administered once , or once a fortnight.

Somatostatin agonists may be injected erally, for example, intravenously, into the bloodstream of the subject being treated. However, it will be readily appreciated by those d in the art that the route, such as subcutaneous, intramuscular, intraperitoneal, enterally, ermally, transmucously, sustained released polymer compositions (e.g., a lactic acid polymer or —glycolic acid copolymer microparticle or implant), ion, nasal, oral, topical, vaginal, rectal, 3O nasal, sublingual, etc., will vary with the condition being treated and the activity and bioavailability of the somatostatin agonist being used.

While it is possible for the Somatostatin agonist to be administered as the pure or ntially pure compound, it may also be presented as a pharmaceutical formulation or preparation. The ations to be used in the present invention, for both humans and animals, comprise any of the somatostatin agonists described herein, together with one or more pharmaceutically acceptable carriers thereof, and optionally other therapeutic ingredients.

The Somatostatin t may be administered by, for example, continuous infusion (using, for example, minipumps such as osmotic pumps), or by injection using, for example, intravenous or subcutaneous means. In one embodiment, the Somatostatin t is administered subcutaneously. The stration can also be as a single bolus or by slow-release depot formulation. The administration may also be by the oral route, for example using OctreolinTM (oral octreotide acetate).

The Somatostatin agonist to be used in the therapy is formulated and dosed in a fashion consistent with good medical practice, taking into account the specific condition being treated, the clinical condition of the individual patient, the site of delivery of the Somatostatin agonist composition, the method of administration, the scheduling of administration, and other factors known to tioners. The "effective " of Somatostatin agonist for purposes herein is thus determined by such considerations. The term "effective amount" in this context refers to any dose of the Somatostatin analog sufficient to mediate Somatostatin receptor agonistic activity, under the ions of administration.

The dosage of active ient administered in a method of this invention may be varied; however, it is necessary that the amount of the active ingredient be such that a suitable dosage form is obtained. The selected dosage depends upon the desired therapeutic effect, on the route of stration, and on the duration of the treatment.

Generally, dosage levels of between 0000001 to 100 mg/kg of body weight daily are administered to humans and other animals, for example, mammals.

A preferred dosage range is 0.01 to 5.0 mg/kg of body weight daily which can be administered as a single dose or divided into multiple doses.

The Somatostatin agonist may be administered as single dose or as ed doses on a periodic basis, for example, several times a day, daily, once every two days, three, four, five, six seven, eight, nine, ten, eleven, twelve, thirteen or fourteen days, once , twice weekly, three times weekly, or every two weeks, every three weeks, 3O or every four weeks.

In one ment of the present disclosure, the Somatostatin agonist is selected from any one of LAR forms, for e, Sandostatin—LAR, Lanreotide Autogel, Pasireotide—LAR, or lanreotide microparticles and the oligonucleotide is ATLllO3 (SEQ ID N06) and the nds are administered sequentially. In one embodiment, the ATL1103 ucleotide is first administered at a dose of 250 mg/day on days 1, 3, 5, 7, l4 and 21, and once weekly thereafter (for 5 to 12 weeks) and the Somatostatin agonist is subsequently administered on the same days at the dose of 20 mg/28days for Sandostatin-LAR, 90mg/28days Lanreotide Autogel, 8days for Pasireotide-LAR, and 20mg/week for Lanreotide microparticles or the higher dose of 30mg/28days for Sandostatin-LAR, or l20mg/28days for Lanreotide Autogel, or 60mg/day for Pasireotide-LAR or 60mg/3weeks for Lanreotide microparticles.

After the 5 to 12 weeks, treatment may be continued (cycle 2) with the same or increased or lower doses of the Somatostatain agonist above, and with the same or increased or lower doses of ATLl 103, and with the same or increased or lower dosing ncy to achieve the d target IGF—I . Post 5 to 12 weeks, the Somatostatin agonist dose may be sed from the low dose to the high dose and monitored at about 1 to 4 weeks to assess IGF-I levels, Post 5 to 12 weeks, the 3 dose modification may be in about 25, 50 mg, or 100mg increments and monitored at about 1 to 8 weeks to assess IGF-I levels. Cycle 2 can be continued if the target IGF-I normalization is achieved or a new cycle started to further optimize dosing to achieve IGF-I ization on a patient by t basis.

Alternatively, the ATL1103 oligonucleotide may be administered once or twice weekly (for 8 to 12 weeks) at doses of 150, 200, 250, 300, or 350 mg together with the above doses of the Somatostatin agonists. After the 8 to 12 weeks, treatment may be continued (cycle 2) with the same or increased or lower doses of the Somatostatain agonist above, and with the same or increased or lower doses of ATLl 103, and with the same or increased or lower dosing frequency to achieve the desired target IGF-I levels.

Cycle 2 can be continued if the target IGF-I normalization is ed or a new cycle d to further optimize dosing to achieve IGF-I normalization on a patient by patient basis.

In another embodiment, a repeat 21 day treatment cycle may be used, for cancer or retinopathy treatment. The ATL1103 oligonucleotide is first administered at a dose of 250 mg/day on days 1, 3, 5, 7, 14 and 21, and the Somatostatin agonist above is subsequently administered on the same days at one of the doses above. Alternatively, in a repeat cycle, the ATL1103 oligonucleotide dosing may be once or twice weekly 250, 300, or 350 mg together with one of the Somatostatin agonist doses above starting on the same day. Alternatively, treatments may be on different days.

After 5 to 12 weeks, treatment may be continued (cycle 2) with the same or increased or lower doses of Somatostatin agonist, and with the same or increased or lower doses of ATL1103, and stered the same or increased or lower dosing frequency to achieve the desired target IGF—I levels and treatment outcomes in cancer 2014/000613 or retinopathy. Post 5 to 12 weeks, the Somatostatin agonist dose modification may be increased from the low dose to the high dose and monitored at about 1 to 4 weeks to assess IGF-I levels. Post 5 to 12 weeks, the 3 dose modification may be in about 25, 50, or 100 mg increments and monitored at about 1 to 8 weeks to assess IGF- I levels. Cycle 2 can be continued if the target IGF-I normalization is achieved or a new cycle started to further optimize dosing to achieve IGF—I normalization on a patient by patient basis.

In another embodiment, the ATL1103 drug may be dosed once, twice, three times weekly, every other day, or daily at doses of 100, 200, 250, 300, 350, or 400 mg/day and the Somatostatin Octreotide e may be dosed daily, twice daily, or three times daily at the recommended mg/day, or the Somatostatin OctreolinTM may be dosed at the recommended dose 40, 60, or 80mg/day, or the Lanreotide microparticles, Octreotide-LAR, Lanreotide-LAR, Pasireotide LAR administered as recommended.

In another embodiment, the 3 oligonucleotide is first administered at one of the above doses once every other week and the Somatostatin Lanreotide articles is subsequently administered on alternative weeks, so that the patient is on a once weekly alternative dosing n, first of ATL1103 and then of Lanreotide microparticles. In a similar embodiment, the Lanreotide microparticles and ATL1103 may also be combined in a mixture and given on the same day. For e, the ATL1103 in a solution in a pre-filled syringe, may be added to the Lanreotide microparticles, and the mixture administered to the subject.

Somatostatin agonists such as Octreolin, Lanreotide, Pasireotide and Octreotide are administered as short, medium or long acting forms to achieve effective dosages as for example outlined above.

In one embodiment, ATL1103 (Seq ID 6) is administered in a dose ranging from 4mg/kg/week to l2mg/kg/week. In one embodiment from 4mg/kg/week to 8mg/kg/week, or 5mg/kg/week to 10mg/kg/week. In some embodiments, 3.5mg/kg/week, 4mg/kg/week, 4.5mg/kg/week, 5mg/kg/week, kg/week 6mg/kg/week, 6.5mg/kg/week, 7mg/kg/week, 7.5mg/kg/week, 8mg/kg/week, 8.5mg/kg/week, 9mg/kg/week, 9.5mg/kg/week, 10mg/kg/week 10.5mg/kg/week, 11mg/kg/week, 11.5mg/kg/week, 12mg/kg/week doses are plated.

As described in e 11, 3 is effective in reducing sIGF-I at twice weekly 200mg dosing and is well tolerated. There was a mean reduction of 30% in sIGF-I ed to baseline in the 4 patients with acromegaly treated at twice weekly 200mg, with a mean ion of 38% in the 3 patients treated that had a body weight below 85kg. As the drug is well tolerated, dosing to beyond twice weekly 200mg to twice weekly 250, twice weekly 300mg, or three times weekly at 200mg, 250mg, and 300mg is proposed. In some embodiments, once weekly 200, 250, 300, 350, and every other day 200mg or even every day 100mg, or 150mg is employed.

To treat acromegaly patients who have failed to have their sIGF-I normalized with first line Somatostatin therapy it is proposed herein to employ combinations with once weekly doses of 200mg, 250mg, 300mg and 350mg ATL1103 as well as all the hereinabove described doses and dosage intervals together with Somatostatin agonist treatments. Acromegaly patients treated with Somatostatin agonist therapy to ize their sIGF-I to the upper limit of normal, may also be treated in combinations with ATL1103 to obtain further benefits.

Unit dosage forms of oligonucleotide comprising 50mg, 100mg, 200mg, 250mg, 300mg, 350mg, and 400mg oligonucleotide are contemplated. Unit dosage forms of ATL1103, sing 200mg, 250mg, 300mg, 350mg, are particularly contemplated.

ES Example 1: Phase I trial of the GHR targeting drug 3.

The primary objective of the Phase I trial was to assess the safety, tolerability and pharmacokinetics (pK) of ATL1103.

The Phase I trial was a randomized, placebo controlled, double blind study of single ascending doses and multiple doses of ATL1103 in healthy adult male subjects aged between 18 and 45 years. In the single ascending dose stage of the trial, 24 subjects were stered four dose levels of ATL1 103 as a single injection ng at 25mg and escalating to 75, 250 and 400mg or o. The multiple dose stage was undertaken in 12 subjects, 8 who were to receive six subcutaneous doses of 250mg of ATL1103 and 4 subjects who received placebo administered on days 1, 3, 5, 7, 14 and 21. Subjects were monitored out to day 35.

Importantly, no serious adverse events were ed in this trial. Two subjects in the multiple dose arm withdrew from the study for reasons not related to safety. All adverse events were reported as "mild to moderate". Injection site reactions 3O ented the majority of all the adverse events reported in the trial. There was one elevation in the liver enzyme ALT reported as an adverse event in the multiple dose stage. Importantly, the ALT levels in this subject ed to normal during the dosing phase, suggesting no residual or cumulative effect of the drug on this safety parameter.

A secondary objective of this study was to obtain data on the pharrnacodynamic effects of ATL1103 on the IGF-I levels in the blood of the trial ts. ion of increased levels of serum IGF-I to normal is the therapeutic endpoint in the treatment of the growth disorder acromegaly, and reducing the effects of IGF-I has a ial role in the ent of diabetic retinopathy, nephropathy and certain forms of cancer.

As defined in the statistical analysis plan, the effect of ATLl 103 on serum IGF- I was assessed as a change in IGF—I levels versus baseline (starting point) readings for those ts who received treatment (ATL1103). Pre-dose baseline levels of IGF-I were recorded prior to the commencement of dosing and then measured at weekly intervals until the end of the monitoring period. This treated group showed a trend in reduction in IGF-I levels from day 14 to day 28, with a significant effect 4 one sided t-test) at day 21 with a 7% reduction in mean IGF-I levels versus baseline.

Other exploratory objectives of the study investigated the drug's ism of action and r pharmacological profile, including the pharmacodynamic effects on levels of growth hormone binding protein (GHBP), insulin-like growth factor binding protein 3 (IGFBP-3), acid labile subunit of the insulin-like growth factor g protein complex (ALS), and growth hormone (GH), as well as in vitro mitogenic and apoptotic parameters.

Notably, ATL1103 had a significant effect on reducing GHBP by 16% (p=0.007) at day 21 and 19% (p<0.05) at day 28, one week past the last dose. As circulating GHBP is produced by cleavage from the GHR, the reduction of circulating GHBP levels suggests that GHR expression is being reduced. ATL1103 also significantly reduced IGFBP-3 and ALS, both consistent with its effect on IGF-I and the fact that they are ted by GH. There was no effect on GH levels. Specific trial details and outcomes are summarized in Tables 3-6.

Table 3 11 i‘ummarv (JfATLl 103 Phase I C]?micaI trial ”$33k fix sm‘sfi'tt 6%. Ski\\““i . ‘x‘ Jixifiri“ '. “3m. 3e3‘ai‘igfifiii . _ . Mi». mgmis sans: . .. J 3 {99$an is!)4 . ws es :3 \«an» 5RR‘NN : ; msns’fi 'Wt‘, '.3‘» 35:02f . {3! .3, et. V.(.

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The main outcomes of the study for the monotherapy and combination treatments arms are as follows: Monotherapy ent Outcomes: 0 ATL1103 (25mg/kg, 2 times ) reduced liver GHr RNA (99.7%, p=0.001), IGF-I RNA (76.2% and serum IGF-I (44.5%, , p=0.001), p=0.003) at week 3 ed to the saline control, with similar sIGF-I reductions as at 1 (36.5%, p=0.0070)and week 2 (41.5%, p=0.004) compared to l saline.

Lower doses of ATL1 103 kg, 3 times in the first week, and then 2 times weekly for two weeks) reduce liver GHr RNA (99%, p=0.001), IGF-I RNA (64.3%, p=0.001) at week 3.

Octreotide (1.25mg/kg twice daily) reduced liver GHr RNA (82.9%, p=0.001), IGF-I .7% and serum IGF-I(25.2%, p=0.03) at , ), week 3 ed to the saline control, with similar sIGF-I reductions as early as week 1 (25.1%, 2).

ATL1103 reduces liver GHr RNA and IGF-1 RNA to levels lower than that achieved with octreotide at the doses employed in this study.

Somavert (20mg/kg, every other day) reduced liver GHr RNA (79.9%, p=0.01) and IGF-1 RNA (43.2%, p=0.05), at week 3 compared to the saline control. (NB: The sIGF-I assay assessed sIGF-I levels in Somavert treated samples as showing > 2 fold increase at 1 week at the higher Somavert dose.

Somavert would be expected to decrease sIGF-I in this study which suggests that there was an issue with the assay and so other sIGF-I data on rt has not been reported here). Somavert at the lower dose (5mg/kg, every other day) increased liver GHr RNA (23%, p=0.05), with no effect on liver IGF-I RNA compared to the saline control.

ATL1103 reduces liver GHr RNA and IGF-1 RNA levels to lower than that achieved with the high dose of Somavert employed in this study.

Combination Treatment Outcomes 3 (25mg/kg, 2 times weekly) combinations with octreotide (1.25mg/kg twice daily) significantly reduced GHr RNA(99.5%, p=0.001), IGF—I RNA (76%, p=0.001), and sIGF-I (42.3%, p=0.005), ed to saline control at week 3.

The ATL1103 ation with octreotide demonstrated a greater activity compared to octreotide monotherapy on each of these parameters. The combination did not demonstrate additional activity ed to ATL1103 monotherapy at week 3 in this mouse study.

ATL1103 (25mg/kg, 2 times weekly) combinations with octreotide (1.25mg/kg twice daily) at week 1 showed significantly reduced sIGF—I (44%, p<0.002), compared to baseline control levels. ATL1103 (25mg/kg, 2 times weekly) monotherapy at week 1 showed d sIGF-I by 25%, p<0.013) compared to baseline control levels and octreotide (1 .25mg/kg twice daily) reduced sIGF-I (15%, p<0.04), ed to baseline control levels. 0 In the first week the ATL1103 combination with octreotide showed ATL1103 was significantly able to r reduce the sIGF-I reduction of octreotide and octreotide was able to further reduce the sIGF-I reduction of ATL1103 at the single doses tested. This showed the combination had an additional effect compared to the monotherapy. o The ATL1103 low dose ation with high active dose Somavert reduced liver GHr RNA (99.5%, p=0.001), liver IGF-I RNA (86.6%, p=0.001), ed to saline at week 3. The ATL1103 high dose combination with Somavert reduced liver GHr RNA(99.8%, p=0.001), IGF- IRNA (87.6%, p=0.001), compared to control saline at week 3 o 3 (lower and higher dose) combinations with the active higher dose Somavert (20mg/kg, every other day) at 3 weeks showed additional liver IGF-I RNA reductions that were statistically significant compared to either ATL1103 or Somavert monotherapy. This was ob served using a factorial structure statistical analysis and a t-test. There was also a statistically significant onal reduction at the level of liver GHr RNA using the t- test.

The mouse ATL1103 ation studies with Somavert showed additional activity at the liver RNA level and support further explorations of the potential benefits of ATLllO3. e 3: Co-administration of an antisense oligonucleotide and Sandostatin- LAR including in subjects in need of serum IGF-I reduction.

ATL1103 is to be subcutaneously administered at 250 mg per day, six times over 3 weeks on days 1, 3, 5, 7, 14 and 21 or 250mg twice weekly for 21 days, and once or twice weekly at 250mg for a further 5 weeks. Sandostatin-LAR will be dosed at 20 mg every 28 days over the same 8 week .

Control group: Sandostatin-LAR is to be administered alone for a similar 8 week period every 28 days to normal volunteers or ts in need of reduction of serum IGF-I.

Pharmacodynamic and pharmacological effects will be assessed as described in Example 1 with similar assays and additional assays where useful, for example, for serum IGF-I and GH.

Treatment is to be continued with the same or increased or lower doses of Sandostatin-LAR, and with the same or increased or lower doses of ATL1103, and administered with the same or increased or lower dosing frequency to achieve the d target serum IGF-I levels, and optionally, GH levels.

Example4: Co-administration of an antisense oligonucleotide and Sandostatin- LAR for the treatment of acromegaly.

Groups of up to 15 acromegalics are to be maintained on their Sandostatin—LAR dose and additionally dosed with ATL1103 as described in Example 1.

Treatment is to be continued with the same or increased or lower doses of Sandostatin-LAR, and with the same or increased or lower doses of ATL1103, and administered with the same or increased or lower dosing frequency to achieve the desired target serum IGF-I levels and optionally, GH levels.

Example 5: Co-administration of an antisense ucleotide and tide — LAR (Autogel) for the treatment of acromegaly Groups of 15 acromegalics are to be dosed with 200 mg ATL1103 once or twice weekly dosing for 13 weeks in patients already on (i) 90 mg once every 28 days Lanreotide-LAR doses or (ii) 120 mg once every 28 day Lanreotide-LAR on the same days as ATL1103.

Treatment is to be continued with the same or increased or lower doses of tide-LAR doses, and with the same or sed or lower doses of 3, and administered with the same or sed or lower dosing frequency to achieve the desired target serum IGF-I levels, and ally GH levels.

Example 6: Co-administration of an antisense ucleotide and Octreotide- LAR for the treatment of diabetic retinopathy Groups of 15 patients with diabetic retinopathy are to be dosed with 200 mg ATL1103 once or twice weekly dosing for 13 weeks and either (i) 20 mg once every 28 days with Octreotide—LAR or (ii) 30 mg once every 28 days with Octreotide-LAR for 13 weeks on the same days as ATL1103.

Control groups: ATL1103 or Octreotide—LAR is to be administered alone for a similar 13 week period to diabetic retinopathy patients.

Treatment is to be ued with the same or increased or lower doses of Octreotide-LAR, and with the same or increased or lower doses of ATL1103, and WO 97938 administered with the same or increased or lower dosing frequency to achieve the desired target IGF-I levels, and optionally GH levels and outcomes in retinal disease.

Example 7: inistration of an antisense oligonucleotide and tide- LAR for the treatment of cancer Groups of 15 patients with cancer associated with increased IGF-I are to be dosed with 200 mg ATL1103 once or twice weekly dosing for 13 weeks and either (i) 90 mg once every 28 days with tide-LAR or (ii) 120 mg every 28 days with Lanreotide-LAR for 13 weeks Control groups: ATL1103 or Lanreotide-LAR is to be administered alone, with patients standard medication, for a similar 13 week period to cancer patients.

Treatment is to be continued with the same or increased or lower doses of Lanreotide-LAR, and with the same or sed or lower doses of ATL1103, and administered with the same or increased or lower dosing frequency to achieve the desired target IGF-I levels, and optionally GH levels and outcomes in cancer. e 8: Co-administration of an antisense oligonucleotide and Somatostatin analogue for the treatment of acromegaly Somatostatin Analogue will be dosed at the doses acromegaly patients are currently using for their treatment, for example, 20, 30, mg/28days or more Octreotide-LAR, or 90, 120mg/28 days with Lanreotie-LAR, or 40 to 60mg Pasireotide-LAR.

ATL1103 is to be aneously administered at, 250 mg per day, six times over 3 weeks on days 1, 3, 5, 7, 14 and 21 or 250mg twice weekly for 21 days, and once or twice weekly at 250mg for a r 5 weeks.

Pharmacodynamic and pharmacological effects will be assessed as described in Example 1 with similar assays and additional assays where useful, for example, for serum IGF-I and GH.

Treatment is to be continued with the same or increased or lower doses of Somatostatin analogue, and with the same or increased or lower doses of ATL1103, and administered with the same or increased or lower dosing frequency to achieve the desired target serum IGF-I and, optionally, GH levels. 2014/000613 Example 9: Co-administration of an antisense oligonucleotide and Somatostatin analogue for the treatment of acromegaly Somatostatin analogue will be dosed subcutaneously, or intramuscularly at the doses acromegaly patients are tly using for their treatment for example as outlined in the Example above.

ATL1103 is to be subcutaneously administered at 100, 150, 200, 250, 300, 350 or 400 mg over 3 weeks once or twice weekly or until a cumulative dose of ~ 1200- 1800 mg.

Pharmacodynamic and pharmacological effects will be ed as described in e 1 with similar assays and additional assays where useful, for example, for serum IGF-I and GH.

Treatment is to be continued with the same or increased or lower doses of Somatostatin analogue, and with the same or increased or lower doses of 3, and stered with the same or increased or lower dosing frequency to achieve the desired target serum IGF-I and, optionally, GH levels.

Example 10: Co-administration of an antisense oligonucleotide and Somatostatin analogue for the treatment of acromegaly statin analogue will be dosed subcutaneously or intramuscularly at the doses acromegaly ts are tly using for their treatment, for example, as outlined in the Examples above.

ATL1103 is to be subcutaneously administered at 100, 150, 200, 250, 300, 350 or 400 mg over 4 weeks once or twice weekly, or over 6 weeks once or twice weekly, or over 8 weeks once or twice weekly, or over 12 weeks once or twice weekly.

Pharmacodynamic and cological effects will be assessed as described in Example 1 with similar assays and additional assays where useful, for example, for serum IGF-I and GH.

Treatment is to be continued with the same or increased or lower doses of Somatostatin analogme, and with the same or increased or lower doses of ATL1103, and administered with the same or increased or lower dosing frequency to achieve the desired target serum IGF-I and, optionally, GH levels.

Example 11: ATL1103 is effective at reducing IGF-l levels in subjects with acromegaly The Phase II trial of 3 was a randomised, open-label, parallel group study of the safety, tolerability, pharmacokinetics and efficacy of two subcantaneous dosing regimens at ATL1103 in 24 adult patients with acromegaly dosed in ATL1103 for 13 weeks (3 months) with two months of follow-up. Two ATL1103 dosing ns were tested (a) 200 mg 3 times in the first week then once weekly therafter (200 mg/week) or (b) 200 mg 3 times in the first week then twice weekly thereafter (400 mg/week). The primary nts or main purposes of the trial were (i) to evaluate the safety and tolerability of ATL1 103 in patients with acromegaly, and (ii) to te the single dose and multiple dose pharmacokinetic profiles of ATL1103 via the subcutaneous route in patients with acromegaly. A secondary, but important endpoint that is also on the trial protocol was the evaluation of ATL1103’s effect on serum insulin like growth factor I (IGF-I) levels in patients. The ary endpoint was the average percentage reduction in serum IGF-I levels at the end of treatment ed to baseline levels for each of the two dosing regimens used in the Phase II study.

In the 4 patients who received the 400 mg per week dose, ATL1103 reduced sIGF-I levels consistently and by an e (mean) of 30% (range 4% to 48%) at week 14 (one week past the last dose) which is the primary efficacy time point for the trial. sIGF-I levels were reduced by a mean of 38% (28-48%) in the 3 patients who had lower body weights (58-83 kg at screening) and thereby received a relatively higher dose per kg bodyweight of between approximately 4.8 and 6.9 mg/kg. The one t showing the lowest sIGF-I reduction at week 14 had the highest body weight (132 kg at screening).

At the 200 mg per week dose, no consistent reduction in mean sIGF-I levels was observed at week 14, although some sIGF-I ion was noted in individual patients.

The time course data (see Figure 1) at the twice weekly 200mg (400 mg per week) dose generally shows a progressive rate of reduction in sIGF-I over the dosing period. This is further support for the therapeutic action of ATL1103 observed in this trial and suggests that continued dosing of 3 at the 400 mg per week dose for longer than 3 months could result in additional reductions in sIGF-I.

Many modifications will be apparent to the skilled person in the art without departing from the scope of the present invention.

All publications discussed and/or referenced herein are incorporated herein in their entirety.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field nt to the present invention as it existed before the priority date of each claim of this application.

REFERENCES Altschul et al., J. Mol. Biol. (1990) 215:403-410 Brazeau et al., e (1973) 179:77 Elbashir et al., Nature (2001a) 411:494-498 Elbashir et al., Genes Dev. (2001b) 15: 188-200 Englisch et al., Angewandte , International Edition (1991) 30:613 Epstein et al., Proc. Natl. Acad. Sci. USA. (1985) 82:3688-3692 Fire et al., Nature (1998) 391 :806-811 Giustina et al., Pituitary (2011) 14:125-133 Guo and us, Cell (1995) 81:611-620 Martin et al., HelV. Chim. Acta (1995) 78:486-504 mery et al., Proc. Natl. Acad. Sci. USA. (1998) 95: 15502-15507 Nielsen et al., Science (1991) 254, 1497-1500 Tabara et al., Science (1998) 282:430-431 Tijsterrnan et al., Science (2002) 295:694-697 Timmons et al., Gene (2001) 263:102-112 Timmons and Fire, Nature (1998) 395:854 Tuschl et al., Genes Dev. (1999) 13:3191-3197 Zhang and Madden, Genome Res. (1997) 7 :649-656 1. Use of Octreotide, Lanreotide, Pasireotide, or Octreolin in the manufacture of a medicament for treatment of acromegaly in a subject having serum levels of insulinlike growth factor I (IGF-I) above normal e Somatostatin agonist therapy, wherein the medicament is to be inistered with an antisense oligonucleotide 15 to 30 nucleobases in length targeted to a nucleic acid encoding human Growth Hormone Receptor for treatment of acromegaly in a subject having serum levels of insulin-like growth factor I (IGF-I) above normal despite Somatostatin agonist y, wherein said oligonucleotide: (i) comprises at least an 8 consecutive nucleobase portion of SEQ ID NO:6; (ii) consists of a deoxynucleoteide region flanked on both the 5’ and 3’ ends with one or more 2’-O-modified sugar moieties; and (iii) comprises at least one 2’-O-methoxyethyl sugar moiety, at least one phosphorothioate internucleoside linkage, and at least one 5-methylcytosine. 2. Use of an antisense oligonucleotide 15 to 30 bases in length targeted to a nucleic acid encoding human Growth Hormone Receptor in the manufacture of a medicament for treatment of galy in a subject having serum levels of insulinlike growth factor I (IGF-I) above normal e Somatostatin t therapy, wherein the medicament is to be co-administered with Octreotide, tide, otide, or Octreolin, wherein said oligonucleotide: (i) comprises at least an 8 consecutive nucleobase portion of SEQ ID NO:6; (ii) consists of a deoxynucleoteide region flanked on both the 5’ and 3’ ends with one or more 2’-O-modified sugar moieties; and (iii) comprises at least one 2’-O-methoxyethyl sugar moiety, at least one phosphorothioate internucleoside linkage, and at least one 5-methylcytosine. 3. The use of claim 1 or claim 2, wherein Octreotide or Octreolin is used in the manufacture of the medicament, or is to be co-administered with the medicament. 4. The use of claim 1 or claim 2, wherein Lanreotide is used in the manufacture of the medicament, or is to be co-administered with the medicament.

. The use of claim 1 or claim 2, wherein Pasireotide is used in the manufacture of the medicament, or is to be co-administered with the medicament 6. The use of any one of claims 1 to 5, wherein the oligonucleotide is a DNA oligonucleotide. 7. The use of any one of claims 1 to 6, wherein the oligonucleotide is a RNA oligonucleotide. 8. The use of any one of claims 1 to 7, wherein the nucleobase sequence of the ucleotide consists of the nucleobase sequence of SEQ ID NO:6.

W0 2014/197938 fififififi 3. . , \ \i W \\\\\\\\\\\\\\\\\'\\\\\\\\\\\\\\\\\\\\\\\\ \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\§' §§§€§$§§§§x mama; 1\\\ $3§tsmz E3 W gei‘imm ._ .. \\\\\\\\\w‘\\\w\\\x~;\\\\\§Aw ._ .. ”a... §§ai§$¥§§ 13 2:} £1 w m m m Wax {at gmfi3r 715825 ‐ Sequence Listing.txt SEQUENCE LISTING <110> Antisense Therapeutics Ltd <120> Combination Therapy <130> 513110 <150> US 61/594532 <151> 2012‐02‐03 <160> 154 <170> PatentIn version 3.5 <210> 1 <211> 586 <212> DNA <213> Homo sapiens <400> 1 cgatatgttc ccaactattc cactgagtcg cctgttcgat aacgcgatgc tgcgtgcgca 60 tcgtctgcac caactggctt tcgacactta ccaggagttc gaagaagcat acatcccgaa 120 agaacagaaa ttcc ttcagaaccc ctcg ttgtgtttct ctgaaagtat 180 cccgacccct tctaaccgcg ccca gcagaaatcg aaccttgaac tgcttcgtat 240 ctcgctgctt ctcattcagt cgtggctgga gccagtacag ttcctgcgtt cggttttcgc 300 aaactcactg gtttacggtg cgtctgacag taacgtttac ctga ttga 360 agaagggatc cagaccctga tgggtcgcct ggaagatggt tcaccacgca ctggtcagat 420 cttcaaacag acttactcca aattcgatac taactctcat gatg ctctgctgaa 480 aaactacggc ctgctgtact gtttccgtaa ggat aaagttgaaa ctttcctgcg 540 tatcgttcag tgtcgttctg ttgaagggtc gtgtggcttc taatag 586 <210> 2 <211> 192 <212> PRT <213> Homo sapiens <400> 2 Met Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu 1 5 10 15 Page 1 715825 ‐ Sequence Listing.txt Arg Ala His Arg Leu His Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe 25 30 Glu Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn 40 45 Pro Gln Thr Ser Leu Cys Phe Ser Glu Ser Ile Pro Thr Pro Ser Asn 50 55 60 Arg Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser 65 70 75 80 Leu Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser 85 90 95 Val Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr 100 105 110 Asp Leu Leu Lys Asp Leu Glu Glu Gly Ile Gln Thr Leu Met Gly Arg 115 120 125 Leu Glu Asp Gly Ser Pro Arg Thr Gly Gln Ile Phe Lys Gln Thr Tyr 130 135 140 Ser Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn 145 150 155 160 Tyr Gly Leu Leu Tyr Cys Phe Arg Lys Asp Met Asp Lys Val Glu Thr 165 170 175 Phe Leu Arg Ile Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 180 185 190 <210> 3 <211> 191 <212> PRT <213> cial Sequence <220> <223> Somavert Page 2 715825 ‐ ce Listing.txt <400> 3 Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu Arg 1 5 10 15 Ala Asp Arg Leu Asn Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu 25 30 Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro 40 45 Gln Thr Ser Leu Cys Phe Ser Glu Ser Ile Pro Thr Pro Ser Asn Arg 50 55 60 Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu 65 70 75 80 Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val 85 90 95 Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp 100 105 110 Leu Leu Lys Asp Leu Gln Gln Lys Ile Gln Thr Leu Met Gly Arg Leu 115 120 125 Glu Asp Gly Ser Pro Arg Thr Gly Gln Ile Phe Lys Gln Thr Tyr Ser 130 135 140 Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr 145 150 155 160 Gly Leu Leu Tyr Cys Phe Asn Ala Asp Met Ser Arg Val Ser Thr Phe 165 170 175 Leu Arg Thr Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 180 185 190 <210> 4 Page 3 715825 ‐ Sequence Listing.txt <211> 4563 <212> DNA <213> Homo sapiens <400> 4 cggcggcggc ggcggcagcg gcagcagcag ctgctacagt ggcggtggcg gcggcggctg 60 ctgctgagcc cgggcggcgg cggggacccc gggc cacgcgggcc ggaggccccg 120 gcaccattgg ccccagcgca gacgcgaacc ctct gatcagaggc gaagctcgga 180 ggtcctacag gtatggatct ctggcagctg ctgttgacct tggc aggatcaagt 240 gatgcttttt ctggaagtga ggccacagca gctatcctta gcagagcacc ctggagtctg 300 caaagtgtta atccaggcct aaagacaaat tcttctaagg agcctaaatt caccaagtgc 360 cgttcacctg agcgagagac atgc cactggacag atgaggttca tcatggtaca 420 aagaacctag gacccataca gctgttctat accagaagga acactcaaga tcaa 480 aaag aatgccctga ttatgtttct gctggggaaa acagctgtta ctttaattca 540 tcgtttacct ccatctggat accttattgt atcaagctaa atgg tggtacagtg 600 gatgaaaagt gtttctctgt tgatgaaata gtgcaaccag atccacccat tgccctcaac 660 tggactttac tgaacgtcag tttaactggg attcatgcag atatccaagt gagatgggaa 720 gcaccacgca atgcagatat tcagaaagga tggatggttc tggagtatga acttcaatac 780 aaagaagtaa atgaaactaa atggaaaatg atggacccta tattgacaac atcagttcca 840 gtgtactcat tgaaagtgga taaggaatat gaagtgcgtg ccaa aaac 900 tctggaaatt atggcgagtt cagtgaggtg ctctatgtaa ctca gatgagccaa 960 tttacatgtg aagaagattt ctactttcca tggctcttaa ttattatctt tggaatattt 1020 acag tgatgctatt tgtattctta ttttctaaac agcaaaggat taaaatgctg 1080 attctgcccc cagttccagt tccaaagatt aaaggaatcg atccagatct cctcaaggaa 1140 ggaaaattag aggaggtgaa ctta gccattcatg atagctataa acccgaattc 1200 cacagtgatg actcttgggt tgaatttatt gagctagata ttgatgagcc agatgaaaag 1260 actgaggaat cagacacaga cagacttcta agcagtgacc atgagaaatc acatagtaac 1320 ctaggggtga aggatggcga ctctggacgt accagctgtt gtgaacctga ggag 1380 actgatttca atgccaatga catacatgag ggtacctcag ctca gccacagagg 1440 Page 4 715825 ‐ Sequence Listing.txt ttaaaagggg aagcagatct cttatgcctt gaccagaaga atcaaaataa ctcaccttat 1500 catgatgctt ctac tcagcagccc agtgttatcc aagcagagaa acca 1560 caaccacttc ctactgaagg agctgagtca actcaccaag ctgcccatat tcagctaagc 1620 aatccaagtt cactgtcaaa catcgacttt tatgcccagg tgagcgacat tacaccagca 1680 ggtagtgtgg tcctttcccc gggccaaaag aataaggcag ggatgtccca atgtgacatg 1740 cacccggaaa tggtctcact ctgccaagaa aacttcctta tggacaatgc ctacttctgt 1800 gaggcagatg ccaaaaagtg catccctgtg gctcctcaca tcaaggttga atcacacata 1860 cagccaagct taaaccaaga ggacatttac atcaccacag aaagccttac cactgctgct 1920 gggaggcctg gaga acatgttcca ggttctgaga tgcctgtccc agactatacc 1980 tccattcata tagtacagtc cccacagggc ctcatactca atgcgactgc cttgcccttg 2040 cctgacaaag agtttctctc atcatgtggc agca cagaccaact gaacaaaatc 2100 atgccttagc ttgg tttcccaaga gctacgtatt taatagcaaa gaattgactg 2160 gggcaataac gtttaagcca aaacaatgtt taaacctttt ttgggggagt gacaggatgg 2220 gatt ctaaaatgcc ttttcccaaa atgttgaaat atgatgttaa aaaaataaga 2280 agaatgctta atcagataga tattcctatt gtgcaatgta aatattttaa gtgt 2340 cagactgttt agtagcagtg attgtcttaa tattgtgggt gttaattttt gatactaagc 2400 attgaatggc tatgttttta atgtatagta aatcacgctt aaag cgaaaaaatc 2460 aggtggcttt tgcggttcag tgaa tgcaaaccat agcacaggct aattttttgt 2520 tgtttcttaa ataagaaact tttttattta aaaaactaaa aactagaggt gagaaattta 2580 aactataagc aagaaggcaa tttg gatatgtaaa acatttattt tgacataaag 2640 ttgataaaga aata atttagactt caagcatggc tattttatat tacactacac 2700 actgtgtact gcagttggta tgacccctct aaggagtgta gcaactacag tctaaagctg 2760 tgtt aatg cacctaaaga aaaacaaact cgttttttac aaagcccttt 2820 tatacctccc cagactcctt caacaattct aaaatgattg tagtaatctg cattattgga 2880 atataattgt tttatctgaa tttttaaaca agtatttgtt aatttagaaa actttaaagc 2940 gtttgcacag atcaacttac caggcaccaa aagaagtaaa agcaaaaaag aaaacctttc 3000 Page 5 715825 ‐ Sequence Listing.txt aaat cttggttgat gccaaaaaaa tgct aagagaagta gaaatcatag 3060 ctggttcaca ctgaccaaga tacttaagtg ctgcaattgc acgcggagtg agttttttag 3120 tgcgtgcaga tggtgagaga taagatctat agcctctgca gcggaatctg ttcacaccca 3180 acttggtttt gctacataat tatccaggaa gggaataagg tacaagaagc attttgtaag 3240 ttgaagcaaa tcgaatgaaa ttaactgggt aatgaaacaa agagttcaag aaataagttt 3300 ttgtttcaca gcctataacc agacacatac tcatttttca tgataatgaa cagaacatag 3360 acagaagaaa caaggttttc agtccccaca gataactgaa aattatttaa accgctaaaa 3420 gaaactttct ttctcactaa atcttttata ggatttattt aaaatagcaa aagt 3480 ttcatcattt tttacttcct ctctgagtgg actggcctca aagcaagcat tcagaagaaa 3540 aagaagcaac ctcagtaatt tagaaatcat tttgcaatcc cttaatatcc tcat 3600 tcatttttgt tgtt gttgttgaga ctcg ctctgtcgcc aggctagagt 3660 gcggtggcgc gatcttgact cactgcaatc tccacctccc acaggttcag gcgattcccg 3720 tgcctcagcc tcctgagtag ctgggactac aggcacgcac caccatgcca tttt 3780 tttgtatttt agcagagacg gggtttcacc atgttggcca ggatggtctc gatctcctga 3840 cctcgtgatc cacccgactc ggcctcccaa agtgctggga gtgt aagccaccgt 3900 gcccagccct aaacatcatt cttgagagca ttgggatatc tcctgaaaag gtttatgaaa 3960 aagaagaatc tcatctcagt gaagaatact tctcattttt taaaaaagct taaaactttg 4020 aagttagctt taacttaaat agtatttccc atttatcgca gacctttttt caag 4080 cttaatggct gataatttta aattctctct ggaa ggactatgaa aagctagaat 4140 tgagtgttta aagttcaaca tgttatttgt aatagatgtt tgatagattt tctgctactt 4200 tgctgctatg gttttctcca agagctacat aatttagttt catataaagt atcatcagtg 4260 tagaacctaa ttcaattcaa agctgtgtgt ttggaagact atcttactat ttcacaacag 4320 cctgacaaca tttctatagc tagc taaatacctc aatcagtctc tcat 4380 tttggtactt tggtggccac ataagccatt attcactagt atgactagtt gtgtctggca 4440 attt aactctcttt atgtctgtgg attttttcct tcaaagttta ataaatttat 4500 tttcttggat tcctgatagt gtgcttctgt tatcaaacac caacataaaa atgatctaaa 4560 Page 6 715825 ‐ Sequence Listing.txt cca 4563 <210> 5 <211> 304901 <212> DNA <213> Homo sapiens <400> 5 atggttttct ttaatcagca cttcagtgat ttacttatta tgtttattgt tctc 60 tcctaactag aatgcaagcc ccatgagggc agcatctttg tagatatgtg gtataaattt 120 tgttccctga ctaa gtttttagaa cgaagtctgt catagtgtag gctcaccaac 180 atttgtatga atgaaagaac atggtgaatg ggaattcagt gttagtttaa aaaaaattca 240 ttaaagggat aatattttat tagaatctta ttaattttac cagtaaatat tgtattaatc 300 agggagatat atatatatat atatgtcata ttcatgagat atat atgt 360 catattcatg agatatatat acagagactt attttgagaa atttgctcac gtga 420 aaactgaaaa gtcaaaaatc tacagggtaa attggttaca gatttaggga atagttgata 480 tgcagtttga atccaaaggc ctga cagaattttc tcttctttgg tcag 540 tttttttctc ttaatgcctt caactgatcg attgaggccc acctacatta tgtagagcaa 600 tatgatttac tcaaagtcta ttgatttaaa tgttaatctt accataaaaa tgcctttgcc 660 aaaaaaatct aaaataatat aaat atctgggtac catggtctag caaaattgac 720 acataaaatt ctca atgtgtcaac tttgctaggg catggtaccc ggacatttgg 780 tcaaatatta ttcaaataaa tttagaattt atcacaaatg tttgatatca taatttgatt 840 tacaaatatc aatctaatac tttattttac agctgaatga tctcagagag caaccccttc 900 cttctatagg ccaagaaatg ttgt gagattagta actaatttac ccaaaatcac 960 agaggaccca cacaggatcc caaggctcct gactaacaat cctatgttct tcaactacaa 1020 taaa acaaaacagc tataaaatgc tactttaagt gttttggcct cttttgtttt 1080 gttttgagaa gaagctttgg cattttatag tacaacagag tgactaaagc catgctctaa 1140 cctcagataa ctgtagattt aggaagttta tactgtggtg ttttatggtt tggggagatg 1200 tgac ctagatatct gcacttgaat atatataatc agaattattt tctaattgtt 1260 Page 7 715825 ‐ Sequence Listing.txt tctattgtct tcaaggcagt ttatattttt tgctaagccc tactggggat gtataaaaga 1320 ctggggaagg gtgggccata ataaggtaag gccataataa atag gttggacaag 1380 ataagttagc caatatctga gtaaagactt caaggaactg taggaggaag caaatgaata 1440 tttgtggaag tgtgtttaaa tcagagagaa aagccagcaa aaagccttca gagt 1500 ctgcctggcc tgcttaagaa acagcaggga tgtg gcag aatggatgac 1560 ccagtgatgg ggaaattcat gggagatgag gtgtggggca aaggtacata gctcacgtag 1620 atgg gccattttga attttattct gatttgaatg gggaaccatt ggagggtttt 1680 gagctgagga atgacatgat attaatttta aaaggaatga ctatggcaac tgaatttata 1740 ctttgggttg ttgttggtgt tggttgggga ttaggggtgg ggtttgtcaa agcaagcaga 1800 ccagttgagt tgagagacta ctgcagtaat ctgagaaatt ctggtggttc agaccaggtg 1860 tctctggacc tctccaagaa caga gttttgaatg tggaatgtga ttggcagaga 1920 agaagtaagg atgatttcaa aggtttgtgg cctgggtaac tggcaggaag tagttgccat 1980 ctactgagat ggaaatgtca cccactgtga tatg tttaaggaga aagaaccaga 2040 gttcagatgt ggacatgtca agtttcagag gtctgttaga catccaaatg gagataccca 2100 gttgttagcc tggagctctg tggagagatc tgggttagag atataaatcc aagagataca 2160 acttttcatt caatttgatt atttattgga cgctttataa actctgtaaa gcac 2220 taacctagac attgcaggta cagatattaa gaatatatag tttctccctc agaaatctct 2280 taattaatga gaaaagcaga catgtcaaca aaactgcaat taaa agaagatata 2340 aaggcctata aaggtgctga tacagggaga attaattaat tccaccctgg ggaatagtca 2400 ggaagacctt cagagagaaa gtaaacaatt gattggaact ttaa gaaggatttc 2460 tgga caaagtagga tcttccaagc gaaa ccatgagcaa atgcagtttc 2520 attcttcaga aggtaaatgt gcat gccttaactt ataacaaatt aatcaactca 2580 atacctgcta cattttccct cacaatttgg aatatataaa gaggcacata ctactatgga 2640 ccaatacctg tatg agattgaagg acctttactt acgaggctta aaaataaaga 2700 ctgcccttca tgtcagttgc aggtttatat ctagttctat agtattaact gaggtgtctt 2760 ttcctatgtt ttctgtgcat gatgactttt taaaaatcaa agacagagca gcagccagag 2820 Page 8 715825 ‐ Sequence Listing.txt agtt caca cagaatggag gatattgctg aacccagatt taaaaaaaaa 2880 aagaagtcaa ttcttatttt tttaagtatg gccctgagct catctcagag cataaacaat 2940 agaatttaga atatctttta tgactccgtc tggcacctcc taaactagat caagattctc 3000 tagctcaggg aagaagggca aaggatgaga aggcacagag aggatataaa cagagaggtt 3060 ggtagtgcca ggctctgaag aaggtccaac ggtc gaca ggcgtggagt 3120 cagcatttga ggcctgtctg gtctctactc ctgccaggac taccctgtca gccagcttgg 3180 caggtatgga ccacccagca ggagtttttc gtgc cctaatcttt tactttccca 3240 agtttctcta tatgggtacc tcccctttta aaagctccag acacagccaa gcaccactat 3300 tgctccagca aagtatgaag ccccagaaat caatggtttg gggaagagtc ttaggggaac 3360 taaatgcctc cttattttta gatgccatag aacaagagca gttcaggatc aataaccatc 3420 ccaccccatg ataaaacacg ccccttccag aatctttcct ttttcgttca ttctaggtgt 3480 ctgtctggaa cagctggggt atttgagcca cagctgagct tctgaaagca ttctaaggaa 3540 cagtttttca cttatctgat tcctttgaaa ataggggtat cttatgtgat atctgctatc 3600 ccagagtctt tggtcctctg ttccttctca agtcttggct tact acttcaaagc 3660 cctatagata tcta aagaaaagaa acttggttcc tttaagttgt attt 3720 gggt ataaacttgg gtttgtgtct gggagctctg ttaaaaaaaa ttta 3780 gtaagccaaa gctgttagaa gcttataagt aagtgacatt acaattgacc gtcagtaaat 3840 agtggaaaga ttgcatgact agctactcct tcagatctga ctgg attt 3900 ttgtactctc tactcagaaa agcatatagt gacttggggt ttgatgctgt acaaaaatga 3960 tatg cacaacttta tgca acacttttac aacttcttgt gaatgaagta 4020 ggcagggctc gcatttgaca gatgagctat gtccagcgtg aggcagagtt aaaacccttt 4080 ctca ggaacttcag gctggggcct gtgtctgctc tccctgcatc cctgtcctct 4140 agcagatacc tctctgctaa catgctgagt gtccttggta aattactcat tctctctgtc 4200 tccgtcttct aacctccaca ataaagtcct tcgtagtttt aactatcttt tcactgtgcc 4260 ccagtgagca ggagtttgga acttgattgt tgatggaaag gcaatatttg gatggctaaa 4320 cacgctttcc aaggtatctc gctgatcttc ctctcattcc tggagatagc taaccttttt 4380 Page 9 715825 ‐ Sequence Listing.txt gtaagtgttt ctttgagtct gtggactgca cttaacgctc ttgtaggtcc tgctttcatt 4440 tggaacgggc aggcggagag gaaggaagtg tattgcaact attt tcctctagga 4500 ggagccgcgc agctcagttg agagtgacac gcaccaactc cagctcctcg ccgggaagac 4560 ttcatcccag caactcggaa gccc gggcggcact ctcc gcagcagttc 4620 tcgaactggc ctccttgaac gtccgcttcg ccttcgcttc tgcaacctgg atctggggga 4680 ctgcgggcca ggcgcggcgt gacccctggt gaacggtggc cgccttttcc cacccctgcc 4740 tcct cccttcccgt ttcaccccgc cccctctctc ctccccaagc ctgacagccc 4800 tgcc aagcagggcg cagccatggg aagaggagga gggctaggga gcggcggcgg 4860 cggcggcagc ggcagcagca gctgctacag tggcggtggc ggcggcggct gctgctgagc 4920 ggcg gcggggaccc cgggctgggg ccacgcgggc cggaggcccc ggcaccattg 4980 gccccagcgc agacgcgaac ccgcgctctc tgatcagagg cgaagctcgg aggtactgga 5040 gtggggctcc gggagtctgg ctttattttc ttgt gccagggggc ctgagggtga 5100 ggac tctagttgtt tatgaaaacg ggaggatctg tcttatatat ttacacggat 5160 aattttttat tccggatgac ttggctgtgc tcccctcctc cttgcgaaga agttgttttc 5220 tgctggtggg ttgttgtaac tagt gtgt gtgtgtgtgt gtgtgtgtgt 5280 gtgtgtgtgt gtgtgtctgg aagttggtga gggcggcagg gagttgcggg cgacagacga 5340 accatcacac tctggcgtct gctctggccc gcgagtagtg tacgtggagg ggtttactcc 5400 ggagacagtt ttgttaaagt cataaaagtt ttgctagtgt gtttctgttt gccatcatct 5460 gcctggctgc ggcaggaact gccgaggctg ctgctgttgc gcggggaaga atccccggca 5520 gcgcgactgg tggg gaggtcgagc tgtgcgcgtg gcgc gcagagcgcg 5580 cggtcttttg cgcgtttgtg cgggccgcag ccgcacgttg gcaccgatgg aactggggtc 5640 agtagagtga cagccaccag tgaa ctggggtaag tggaaattgt ccga 5700 cctcccccag cttttgacac actagtggtt gtaaaatcaa ccaggcttaa agttttgaca 5760 gaactgccag aggctgcggg tcaatggggt ggccgcgtgt ctagggagag ggcgctggcg 5820 gcgcagaggg tgcggggcag ggcacttgcg agtgcgtggg gaagtctatt tggggcgagt 5880 gctttatata tagcccgagg ggatgcctgc tgagaccgag ctgcgggggc tctcggtctg 5940 Page 10 715825 ‐ Sequence Listing.txt actg tgtgtcctga atgagtgtac gtgtgcgctg tgtgtgcgcg cgcgagtgtg 6000 cgcctgggga ggcgtgtcgg cgcctgagcc agtagggtgt gcagggtgga agaggccaca 6060 gaggtgccgc ctgtctgttt gtgccgccag gagaccttgg aagggacaga gaaaggtaac 6120 ggaaggccaa agtgttggga agta gtttctgcat aggattaagt attaagggct 6180 ttaaaataac taaacgcatt gccctgagtg gctgaggact ggaagtgagg ttttggggag 6240 ttctcaggag atgg gagggcgttt gggaggtcta agggatgtgt aatatgtgtg 6300 agtacagaac ttcggagaca gacacaggtt ggagctatga atttgaaatt ttcagggtgc 6360 tgctgtccac agtccaggga ctggctggtt tcagaggtat tcaggctccc tggtgtgtgt 6420 gaag acactcatct gcag acatgggata ttgtggcagg tcaggctctg 6480 tttcctgagc aactggtgtt ccaggctagt ctga atcaccctag aagtgtcttt 6540 tttctgatga taaatgttga tcca gaaattaaaa tgctggatag aaacaaaatt 6600 gatgcagcag acaggattgt tgattctatt tattcagtga ttgggagctc tttttccttt 6660 tgagaaaagc aaagctcagt gtttccagat tagatttcaa ggagtcttca gctatctaca 6720 cttc tgggcctttg gatggagctg gaaggatgtg ccta aagacctttg 6780 gaagacatca tgtgtagctt gttg tcccgtctct catcatcttc ttccaccctt 6840 ataaactttt tgttttgcat taatctaagg aaagttggtg tgtcaacatt tagctttttt 6900 ttattggagt aaatatatca cagtgaaatt atagttatgg tctcctgaag cccatggaaa 6960 gccaacactt aatgggcaaa ggtgtgaaat gaaagtctat aaatgcaatg acaaagtgac 7020 agtg cattcttttt tcaaaatgaa cataactgtg ctcacaaaaa tttgttttag 7080 ccaggctttg ggcccatgtt ttttattatt agtttttaaa cagcagactc cacatcataa 7140 accactttaa aatggatact ctcc tgtatgctat ctctggcgcc tgcttaaaca 7200 gatgtttaca gtgcttggta acctatggga ttgtcatgtt gagtatcttg ttagctcagg 7260 acataatgtt tatagcataa tataataaat acag ttgcagcgtg cttcttccaa 7320 gtgcatgaag caaatcttgc agcagggaaa ttgc agttggtcca acttggctag 7380 ccttctttgg ctatctcctg gtgagcaatg taaa gataaatgtg agtgacgtag 7440 tgagaaagtg ggacagtaaa ttgtttagct tagtgaaaaa agcatggatt atgtttttta 7500 Page 11 715825 ‐ Sequence Listing.txt aatctgctaa cctgaagatt acacttctca ggtcgtacca ctggcaaatt ctat 7560 gggaatttgg tttgctttta aagagcaatt tttaaaaagt atgtcagtaa tgaaaataac 7620 ttatatttct taatgtgttt atgtgtgtcc atacaagcca atactttttc ttctttaaaa 7680 agaaccctat aatttctgtg gtaattattt aaatattatg agcattcaaa tctcctaatc 7740 accttttcaa tcttcaattg ataagaatcg ggta agactggagt catccctcag 7800 ccaattgtgt aaacaagaca gtacagaatg tctttctggc aagtaatttt tttcaacctg 7860 aaacagataa tataaataat cata aaagaattac ttaagatgat aattacttta 7920 gaggtaatta tctggtgcat gaacctctat ctgtgaaaat ggtctagtct atctcttatt 7980 ggaaataatc agttggaaat tttt cattggtcag ctag gaaagattca 8040 tttctagaaa gttcttatac tgaatcaaca ttttcttcca tccacttgcc tatccttcag 8100 cagctgacca caatgaatct agtctctttt ccctgtgttt accatacttg aaaacaaata 8160 ttatcctcct atcc ccttttgcct actcttggag cagtttttca tccactatag 8220 accc tcctctgcct tgaacaagat gcccttgatt gtacattctc attgtattag 8280 tctgttctca taat aaagacatac gtgagactgt gtaatttata aagaaaaaga 8340 ggtttaatgg attcacagtt ccacatggct ggggaggcct cacaatcatg gcggaaggtg 8400 aaggaggagc atgt cttacatgac agcaggcaag aaagcatgtg caggggaact 8460 gccctttata gaaccatcag atctcattag acttattcac tatcatgaga acaacatggg 8520 aaaaacccac ttccatgatt taatcaactc ctactgggtc ccttccacca catgtgggaa 8580 ttatgggaac tacaattcaa gatggcattt gggtggagac aaagccaaac catatcattc 8640 cgctcctagc ccctcctaaa tctcatgttc tcacatttca aaaccaatca taccttccca 8700 acagtccccc aaagtcttaa ctcatttcag cattaactca aaaatccaca gtccaaagtc 8760 tcacctgaac caaggcaagt cccttccacc tatgagcctg taaaatcaaa agcaagttag 8820 ttactttcta gatacaatgg aggtacaggc attgtgtaaa tatgcccatt ccaaatggga 8880 ggcc aaaacagagg ggctataggt gcaagtccaa agtctaatag ggcagtcatt 8940 aaaccttaaa gttctgaaat gaactccttt gacttcatgt ctcacatcca ggctgttttc 9000 ggca gtgg cttttccagg gtgc tcag cccctaccat 9060 Page 12 715825 ‐ Sequence Listing.txt tgggggtgct ggggaatggt ggccctcttc tcttagctct actaggcagt gacccactgg 9120 ggactctgtg tagaggatcc aaccccacat ttcttttcct cattgcccta gttg 9180 tttatgaggg ctctgcccct gcaggacaac tctgcctgga catccaggca tttccataca 9240 tcctctgaaa tctaggtgga caaa cctcagttct tgtcttctgt gcacctgcag 9300 cacc acatggaagc ttccaagact tggggctttc accctttgca gccatggcct 9360 gagctgtacc ttggcccctt ttagacatgg ctagaggggc tgggacacag aagt 9420 acctaggctg cacctagcag gcccagaaaa ccatttttcc ggcc tctgggcctg 9480 tgatgtgagg ggctgccata aaggcctctg tctg gagacatttt ccctattgtc 9540 ttggtgacca acatttggct tctcattact tatgcaaatt tctgcagcag tcttgaattt 9600 ctccccagaa aatgggtttt tcttttctat ggcatcatca gcttgcacat tttccaaact 9660 tttatgctct tttcacctct tgaatgcttt gctgcttcta aatttcttct gccagatacc 9720 ctaaataatc tctctcaagt ttcc acagatctct aggacagggg gcca 9780 ccagtctctt tgctaaagca ttaacaagag tcacctttgc tccagttccc aacaagttct 9840 tcatcttcat ctgagaccac atcagcctgg ttgt ccatatcact ataagcattt 9900 tggtcaaagc cattcaacaa gtctctagga agttccaaac tttcccacat cttcctgttt 9960 tctgagccct ccaagtctct agaaagttcc aaactttccc acattttcct gtcttctttt 10020 gagccctcca tactgttcaa acctctgcct gttacccagt tctaaagttg cttccacatt 10080 tttgggtatc tttacagcag ctct accattacca acttactata ttagcccatt 10140 ctcatgctgc taacaaagac atacccaaga ctgggtaatt tataaagaaa attaggttta 10200 gcac acat gagg cctctcaatc atggcagaag gtgaaggagg 10260 aataaggcac tcttacatgg acaa taaggcatgt gcgggggaac taccctttat 10320 aaaaccatca catctcatga gacttaatca ctatcgcaag aacagcatgg gaaaaactcg 10380 ccctcttggt tcaatgacct cccactgggt tcctcccatg acacatgggg attatggtag 10440 ctacaattca agatgaaatt ggga cacagcaaaa ccatattact gactgtccct 10500 cctaatgtgt gttttctaaa caaaagattt ataatttgta gttctgaaca ttctatatct 10560 attaagacag tttaatatta atgaaattct ttagccattt cattacgctc ttgattaatt 10620 Page 13 715825 ‐ ce Listing.txt tcatacctat gata acttgttctt ttcagattat taatcatcca tagtcaaagc 10680 ataa tagcttcaaa acattttttc atgcctgaat gtactataaa tttatggaaa 10740 gtataatact gtgtgggtaa ttct ataaacagtg caaatagtga cttaatttct 10800 ccctatcaag gaatatcaac cccaaatata ccgaaagtag aatgttccaa acaa 10860 gttgaaacta catgttatag acaggtaggg actatgatgt ttca taggcctcat 10920 tgtgtctgct tccatgaaca tgagtcagta ctagcaatca ggcatttatt gaaggcttgt 10980 tctgccaaag tcccagagag tatgccatct ggccttaaat gaagtgaaag tacatcaaat 11040 aaagatactt ccttgggcaa ctgggattta agatgtgcat gcaggacatg tctaagtcag 11100 ccatctactt tttctcagga ggtaaatggc ttgccaatgc cacaggaaag tctaaagtgt 11160 tcacactcca taagcaggtc ccatgtcctg ttgtaggtct ggacaggagc tggacaaagg 11220 ccctgttact cttagcttac caagtcttag ctgccttgga agaagatagc aaatctggct 11280 tatccagagg agaggcctga catt gggcacctac ctggtgtgac tgatttctct 11340 tttatgtatc tgtcttgggc ttccagctaa attgtgaatt ccccttgcca ccaagctaag 11400 aatctgccac agcattgtct tcctgcacac acacacacat acacacacac aaaaacatat 11460 atgttggatg atgaagagac aatgtcagtt tttcagcaag tctgaatgtg aaacaaatgg 11520 ctatgtttct tggtgcagtg gggtgggagg atgagagaga aaaaacaaac ctgtgatata 11580 catc tgagcctacc aaaagccctt tgagagacct ttgatcaaga caaggggata 11640 atcatagtgt tgtgcactta gataaaattg tccatgctag gtgt gtgtgtgtgt 11700 gtgtgtgtgt gtgtatgtgt gtgtttcttc actttatccc cagcattatg gtctcaattc 11760 atacacattt gcttttttgc tttattctag tctgatatga agggaagaaa atga 11820 ttcagttcct ttttttacat ttcaaacatt catttcacta ctccccacct cccagtcctc 11880 accccccaaa attacaagag acccattggc aagtacttgg acatgcaatt ccaa 11940 aggtttactt tgctataaga aacgtctaag tgat ataatatgaa ataatagtaa 12000 attagatgtc aagaaacttg ggtcctctcc aagctctgcc tttaatgggc tttgcagttt 12060 ttgccaacta cttc ctgggcttca tatttcttgt atgttaaaaa caagcaaaaa 12120 gtaa acaaaatgac gaat tctcttcagg gctattgttt gaatccattt 12180 Page 14 715825 ‐ ce Listing.txt aattatcaaa tttctctctt cttttaaatg taagcatcaa aaaatgtttg cctattttat 12240 tctctcatca ttaattttta atcaattaaa taaaatagat aaaaatttta tcaaaaccat 12300 gcttcttgct ctaa aacaatgcaa ctcatcacta gcag aaagtctttc 12360 tgaaatattg tttttctctt ttgttgttgt ttttttcttt gtgctaaaga aaattcattg 12420 atgagtacca ggttcttcaa agaaggatgg aaaagtcatt gttttttagt ctcaacttct 12480 ttcttcagtg cttcttccta ccttttaata taggcaaata aagccttagg ccaggcacta 12540 ctta gtaatgattc aggt agtgattttg tcagaaattg ctggctgcat 12600 gcttttaatc agcatctaaa cttaccttca aatactccat tccaaaatca gcagataact 12660 tcttctacag agtctttcaa acttccagat gtgtttactg ttttgattag ggctttcttc 12720 ttttgttgtt gataagactt cagccagttt tctttaggct aacattatta tattcccaat 12780 gaattatact tcttaggttg tgaatttgtt taaagataaa tctatctcca gctggctggc 12840 gtaa aaaggggtat cctagggaag aagtgcactt cacagggatt cagtacaggt 12900 gtagagaatt ccctgataga gaattggaac acatcaagag aatt gaaaaggtac 12960 ttttatgtac ttatccatgg tggacaacct gtgtcctagg gaagaagcgc atttcacagg 13020 gattcagcac aggtgtagag aattccctga tagggaactg gaacacatca agattttgca 13080 atctgaacag gtacttttat gtacttatcc atggttgaca acctactgtg ctagacattt 13140 gctgtagtaa ctccttgatt ttttcctcgg ttgtttataa aattaaacat ttgaagtagc 13200 aaaa gtcttaaaag aagcatctcc tctattcctt tagaatacag tatattaaac 13260 aagtgataaa gtccaaagaa aaatccttat tcttttcttg ctttaaaaaa tgcactttat 13320 tttattaagc attatatcta aaaa ctttgaattg ccatatcaat gaaagtagag 13380 tgttatcatt acaaaacaga atcgcagata gttctttccc tgtgcttatt gagagaaaag 13440 gtgcataatt gatgctgtaa atgatcatct tgaatttgat gatggctggt cctc 13500 agtcagacat tcaattttga ttgccattgg tcagaaaggc agcctttgtt cttcgtcact 13560 atgtggcaca taat tcaccctatc agctgcttct ctgcacactt tatg 13620 tgattgttat actagaaagc ctctaagttg ctaa tgaagactaa aaag 13680 catatgtgaa tgataaattc tgtaaagacc atag agcctctgca gtggcttctt 13740 Page 15 715825 ‐ Sequence Listing.txt cccctgggga tagaagaaga taccagaatc cctgggcaag taga taaaggaaag 13800 gcatcatttt tatacctagg aaatcagaaa gattaaagaa agagaagcaa gaataaagaa 13860 gaactactac tttcatagtt cattctttca atgtagcacc ttatttccca tagagacatt 13920 ggtgaagcca tgcttttctt tgccatagaa taggtgttca attt tgcaggtggc 13980 cttaatatgt agtaaaacat acagaaatat ggaagcattg acaagaagtt tgtggataat 14040 ttgagggcaa gtag ataggatcag gttcataatg caaatttgct attattctcc 14100 ttagattaat actc aaacttcatg acctgctttc caaggtgtat caca 14160 gaaa catttagaag tttttagtac ttggagcaag atggatatat gtttcacatt 14220 agga cttagtagga cttgggagac atatctactt tgccagatct tagtatactt 14280 attatggagc atgacatttt aattctcttt gcttttgtcc tacaaagttt agtgttttaa 14340 tttatttttc tcggtgcata tagggagaga attatttata taatctgaaa agtactttga 14400 aaactacttg ggaaaatatg ttgaataaat aagttttttt ttaaattagc ctacaggatg 14460 taagtctggc caggctagtg gtatttttgg tatcattgtg aaaaatcaaa aacagaacat 14520 gtatttatca atccattagt gtgttcccag gaatgtgcta gacactaggg aattaaaaca 14580 tgactcttga ctttagtacc aagcattcaa gctagaaggc aacactatta atgtacattc 14640 atggtgtgat tatggaacag tcgatgactg tacaacttaa tgaaaagttc attagagact 14700 ataaatgcta catttattta gagagaagga caatctgttt ggactgaggg attggaagag 14760 tggccttcat gggcaacatg gctcctgagc cagtacttaa gatatggtat tttttttttt 14820 tttttttttt tttggttagg tagaagggtt ggagaggttt catgcaagga gttaggaact 14880 cagg aggcgtatct tgagttcact ggggttactg gtaataggga ggaggcagag 14940 agtaccaggc tgtggatttg gttg cttc ccattgctta ttatggtcgc 15000 tagg ctcatccctt gggtagggct attggagtgg ccaccctgac gctg 15060 attggatagt ggtggctgct gtgtggtatt tcagcacatt ttct gaacattatg 15120 taaattcagt ctgaaaactt ctttcttaaa caatgttcca agaggcctat taaagatgcc 15180 aacaatatga cttccattca agaatatgat cttgaatggg ctttacaatg gcagagctga 15240 cctgagatta cctcctctgc tcctgctctc tgtg ctgatgctga cagtcctggc 15300 Page 16 715825 ‐ Sequence g.txt ccaatagagc catagggcct actt gagatcatct accagtggct gtcaaccaag 15360 ccactccttt ctgctaggta gtgcataggg acattgggaa atacagttat tataagaact 15420 ggaaagagtt gtaggctttt ggtgcctgaa gtcagaaatg ctaaatttct gtgatgccag 15480 gggcagtcct atataagaaa ttattgtgcc tcctcaaatg ccagtagatc cctattgaaa 15540 tacttgagtc tcatatcctc actttattta taggtgagga aatgggaggc cctgagaagt 15600 gacaaaactt agga ttaaacttca cagtctcagt gacagattta taactcaatt 15660 cttttagttt tctttcaaga gctcttgttg cagcaccaca gtccctccta ttaacatggg 15720 ctataactat ggaatagcat gttgtttatc attt ttatagaagg atgatagtta 15780 gctatgttaa ctatctgaat aatg tgaattgaga taactggtac agca 15840 gttctttcgc ctgggaacac acacagattc acctgtaaat tagggttggc agatgcctgt 15900 tgagatgtca accatagcca aagcttacaa attggttgac tttttggaaa gggcatggag 15960 taggctttgg attcacacaa atctgcttgt ggat ttgaatacaa cccttcttat 16020 ctttactatc tttgtgactc tcagccaatt aaactctctg agctttatct aaac 16080 agttgattat tcttatttca caagcaatga gtcaaaatag tgcctggcac atattgggca 16140 ctgcagatat agagaattcc ctacagtatc tttttgagca cttg aaaccttcac 16200 ttataaaaga ccctcttgat aacagtcgct atttttttct cctcctttcc ccaaacaacg 16260 aaactagggc gagt ccctgaagtg tttactttgt ttgaactgtt gagatttccc 16320 tcctccagaa gagtcctgct ggccagagat gagttccttt tgacttctct gtcaacgtgc 16380 ctgtattatt gtcacatagt gaaa gatatatcta gatgattatt agcaggttat 16440 gaaacttaga ttttaaagtc aataataaaa gccattcctg ggtagagaag tttttcagag 16500 agatttctac cttgccagcg atgagagagc ctacttaggt gaggtgaata ctttaggcaa 16560 gttaagggat aacacaatat aatttattta agtaagtttt ttatctggga ctaatttcag 16620 gtttgcagaa aagttgcaaa agag gtcctgtata ttcctcacct agtttcccat 16680 gttgacatcc ataatcatga tatatttgtc aacactaaga aaccaatgtt agtacagtac 16740 tattaactaa aatccagact tcatcctaat tcccccagag cttccactca catcttcttt 16800 tctgttccag gattcaatcc agaagcgtgc actgcttttg attttatgat ttttaaatac 16860 Page 17 715825 ‐ Sequence Listing.txt tgtgcatgtg cttttttaat ttgggccctc gtta aacttaccgg cctttgtaac 16920 cagatagcaa gttctgtaac agaaaataca atgatgttga atccaacatc atgctgggca 16980 caaagtatgt tctccaaact aattaaattt atcacagcaa caagaacaaa gttttactca 17040 gcgtacatat gtagctgagt tggt aagctaagag gtagtcataa gagtgggata 17100 acttggaaga aatttgattt tgaatgtgtg ccctgaacat tggtataaaa cccc 17160 taaatcatat atgaactgag tctgtacact gtgcctagca ttgtgtgtgc atatcacact 17220 tactcctgat aactgtaagg cacatagcct tgagtaactt agctgaggaa atgagaccaa 17280 gggaagttaa gttacttggc cagggattca cagctagtaa cacagctgag attaaaacat 17340 atgtttttct ggcttcagag cctacactcc taatgctgta ttcaattact cttc 17400 tccacttgct taacccctat tcttggtgtc ctttttctag gtatacagaa tttgaaaact 17460 atattgtcaa actacagcag acctggatgc taca cttctttgtg agctggatta 17520 agcc ttgaatttgt ggattatttt caaaacctgc ctaacatctg taaaacatgt 17580 tgttttttta atatgtagat atccacataa attgaccaca atgctcttca ccca 17640 taatccaata ataaataaat ttttgataca tggctaataa caggcacaga agcatctcca 17700 aaggacagga tatt gtgtaataat ttaaagtatt ttatgattgt ataatgtgcc 17760 tgagttttgg atagttgacc tctc agtctttaca tagttactgc ttttttaagt 17820 gttacatgag ggatgtggaa tattcagtgt aacatttgac taatctttat gttttgagtg 17880 gcccaactga aaattaccct tggttgcctt ctgg gcatgatgtt caaaactaga 17940 aattcttgca aattatttga gctttggctc tgggaagata aacaacatga ataactaggt 18000 taaccagggc tgaaatttct ctaacctata attctaaatt agaa tgggctttag 18060 ggttttttgt ttatttttgc tttgattaca agttgttgga agcctagagt tagtatctaa 18120 taacacaatc aaac acaaattatt ggctcagaat gatatctaat ttctaagaag 18180 atatgaggag gcaatcatgt aaaaacgtgc ttttcttcct agaaggaata gatt 18240 ggccaaaagg cttt agagtctaat gtttagagca ttgcatattt ttaaagaaga 18300 catattacct tttagaacat atgtaggaaa ccattttctt tgcttatatg taaa 18360 gttgtcatgg ttttaaaccg tgaccttaga taccttatag aagtaattac aggcacaatc 18420 Page 18 715825 ‐ Sequence Listing.txt tgtgaatgaa gatttgcaaa ctatgcttca ccaagcctca gggactattg gatgtccaga 18480 agcc atgttggatg tcttatgggc cttcagtcct gcaaagtggt gtgctttcat 18540 gttttacaca cagcagttct gagaaaattt aagttgaaaa aacagcctct cttcttatta 18600 tttttatatt tatttattta tttatttatt tatttattta tttgaaacga aatcttgctg 18660 tgtcaccagg ctggagtgca gtggcgtgaa cttggctcac tgcaacctct gcctcccagg 18720 ttcaagcgat tctcttgcct ctgcctcctg agtaggtggg actacaggtg caggccacca 18780 cgcccagcta atttttgtat atatgtattt ttaatagaga cagggtttag ccaggttgcc 18840 caggctgatc ttgaactcct gagctcaagt gatcagccca cctcagcctc tccaagtgct 18900 gggattacag gtgtgaggca ccgtgccgag ccatcctgtc ttctgaaaaa aaaaaaaaag 18960 caaacaaaaa tgtttaagcc tggtatatat atat tgcataagct acttttctga 19020 ctgcctctct ttagaaattc ctctgatttc tagagaaaaa aaaatcgcat tagctttttg 19080 gtttctaaat tcaggctcac tttagtaact gctagattat aaactcttag aaggcaaagg 19140 gctatgtatt ttgt ggacactcaa ttagtttgct taagcaatta cttctgtgta 19200 agcaacatta atgaagtgct tactatgatc aagggctata ccaagtcctt ttttatatta 19260 tttaatccca cacaaaaccc atgatcgacc taattgtaca cttggtgaaa ctatgatgta 19320 gggaggttaa tgtt caagaaccca cagctggtaa gtcgcacagt gtattcaaac 19380 ccagatcttc ctaattgcaa atgtgtccaa ctcccatgct tctaaccact gcctatgtga 19440 tttg aaattcctcc ctccaagaag tggaatttaa ttccccccgt aatg 19500 aaac tcaggtgact catttctatt aaatggagta aagtggaagt gaagatgtgt 19560 ggctttagcg actaggtcat tcaaagtggc tcctgtcttg ctgt ctcttatacc 19620 tattgggcat ttaatctggg gaaaaccagc tgccatgttt tgagctgctc aagg 19680 tgaa aagatactgt taca gacagcttca aatgaggacc tgaggccctc 19740 agaccagtag ccagtatgaa actgaagcct cttgaccaca gcctccatga tgga 19800 atcttgaccc cctagtgaac cacagcctcc atgagagtaa aattcaagat ggagccttga 19860 cacccagtgg agcctcgaga tgactgcagt cttccaccaa cagcttgatt catgaaagac 19920 catcagccag agccacccag tgat tctaggcccc tactcctaga aaataaatat 19980 Page 19 715825 ‐ Sequence Listing.txt ttgctgtttt gactgccaag tgtttgatta atttgttacg cagcaataga taaataatgc 20040 agcctaacac tgtcctggtc atttttaaaa aagaaattgt tttaatttta ctaaatcaca 20100 aattttaaaa cattgataca gcaaggagaa caga aaaaaaatgc tgccaaattt 20160 taaa atattaatgt aaca tcatagttac aatgacatct ctaggattga 20220 ggattttgta agtcaaaggt cagctgctta aaaaacccat aattttaaaa ggaaggatat 20280 taataataac tgcattattg aacatagata gcattttgaa cttttaagaa atcctcatgg 20340 gaaaactcag atct gtttggtaag ttatcactca taatcttaaa ttgttaggtg 20400 catgtttgca ctttccatga tttgaagagg aatataaagc aaagttgaat tttaacctct 20460 tccctaatga ttttactcag cttttcaaag gggtcctaaa agctcagagg tcaagtcatt 20520 tcttggtttg ctctacctga caaattgcat taactctgct ccac ttgcagttta 20580 ataaatgact tggactttga ttaatatctt tagtgcttaa gcccaagaat ttgtataaga 20640 gata tagtactgta aatttatcta aagatggaca ctggaaggta gaaggagata 20700 tgtt ggtttgggta catgtctagg tactgaattt ggatcatcat ttac 20760 agaagatact tgttgacttg tcttttaaaa aatatgtgaa agtgattttt taatatattt 20820 acaaagtgat gatt taaggaattc attcatgaag tggatatgac tagttcttgt 20880 ttagtattca gaatgactgt aaaatagaaa tgctgatttt ccttgcccag attgtagaac 20940 acagatcaaa ccctcctagt ccttccctta aatgtttttt ctccatacag cttatgccct 21000 gagttctcaa aacatttttt atattgaact ggactgtata gtatatgcct gaccctgatt 21060 catgggatta tgctgcaagg gaatataaag atgaatattg atagcctgag tgtgaaaatt 21120 catcattact ctcatcctca ttcattaatt catttgttca ttaactcata aacacactaa 21180 ttgattcaac agatatttat tgaacgttta cactttgccc agtggagcac tggactaggt 21240 gctagcatag aagc aacccagaaa tagcctctgc cttgctgcat ttcatagtct 21300 gaga ttaa ccaagtataa tttaaaattg ttttaagtaa tgtgaaataa 21360 acatatatga gaacttgact ggta tatttgatgg ttagggaaag cttcaaaaat 21420 gggatatttg agatctaagt gaaa agaaagagca taatgggtag aata 21480 ggatccagga agatacttag tacttctgag aactaaaaac agtcaagtca gtgtagtcag 21540 Page 20 715825 ‐ Sequence Listing.txt agttcaaaga aggagaaaga acatgatcca agaagaagcc agaaaagtaa gcagggacta 21600 catcttacac gatgatgtag gctgtatttt agtttttact tatcttaaga gcaatagaaa 21660 accattgaag ggtttgaagc aggggagtga cagg tttt aaggaggtca 21720 cctgctctat tatgaagcat agga ggatggaaag agatattcag ggagctggtt 21780 tatgagtctg ttgtaggcca gaggtattgg tagcttggac cagggtgatg atgctgaaga 21840 ttgaaaggag ttaatagatt tataatatat ttgtgaagta aagttgactg tacttagtgc 21900 tgacttagat agtactggtg agggatgtca tggtaaactc actg ggcttcttca 21960 actgagtgga taga gggagaccag gtaaaggttg aaggaaagtg aggaacagta 22020 gttcagtttg gggatatttt gatttggagg cctttttaag tcaa agagacacag 22080 tgcagtcttg agtcctggat cagaggagat acctcaatgt ataaatttgt aagacaatgg 22140 caca ctattaaagc cactgaggta agtgagatca tgtacagagt gaaaatgaag 22200 tgagagaaga aagcataagt ctgagccatg agaactccaa catttaaagg ccaagtggaa 22260 aagttgacaa gagtgggaat tgtgactggg gtagatgcta gaggggcatc tcagaggcca 22320 aggaaagaga atcatttaag gtgctgatga ggggtaaagt aagaaggtcc tgtaaatgtc 22380 ctcttggatt aataaatttg atgttttgaa ggactttagg gagaatgagt ttgttgtagt 22440 gatgggggca gaagccagaa tgaagtgtca tgggaaatgg gtggaagtct tgaaagagag 22500 acaatgaata tagataactc tgtg gtcaagggaa acaaaaagga taaggcttta 22560 actagaggag gagt taaaggagga gttttttttt ttttgagacg gagtctcgcc 22620 atgtcgccca ggctggagtg cacg atcttggctc actgcaagct ccgcctcctg 22680 ggttcacgcc attctcctgc ctcagcctcc tgagtagctg ggactacagg tgccctccac 22740 cacgcccagc ttta tatttttagt agagacgggg tttcaccgtg ttagccagga 22800 tggtctcgat ctcctgacct catgattcgc ctgccttggc ctcccaaagt gctgggatta 22860 tgag ccaccactcc cagccaggag tttt taaagatggg agacttgagc 22920 acatttgaac aataatgggg aagaccagtg gggaggatca ggggtggcct agac 22980 agagggtgga taaataatca tgtaggattc ctgagaagat agaagaagtt ggatccagag 23040 cacagcaggg agct ggccttggag aggagagatg atctctatcc tctattctag 23100 Page 21 715825 ‐ Sequence Listing.txt aaggaagcca aaggtgatgt gtgcagatgc agaggtgtgt ttgatgtggt gaagccaagt 23160 caaaggagtt tttgttcgat gccttatatc tgctccagaa agcagttgag actg 23220 agacagggag agagaaaggg gctggcatac taggaaggaa tcat ttcagatatt 23280 tgaggaggac agagtaagtt ggaatatgaa agggaataaa tgagtgaaat ttagtaggac 23340 tgctagtcac tgcttgaagg ctcagctgag gatc atgaattcat ggtactactg 23400 ttagaattat atat atgagccttt ttggaggtgc tcagcagttt accagacaca 23460 gaaaaacagg ttcatctagg attt tgtcagagag tgaa aagattgcaa 23520 aggagtttag ggca tgggcaaggg agcttctgga gtgataaacc aggaatctaa 23580 gcctgctagg gagggacata tagacaggag aaggagagta tagagatctt ggtt 23640 agaggaaatt tgtaatcaaa gtggttgatt aaacaagaca gaagtatagc tgat 23700 cagcccagga accc aatt aaatctgtat ttctgggtgt agggcccatc 23760 ccagtttctc aggagattcc agtgctttcc ttaagggaga atattgatat aactgttatt 23820 aagactattg tgaaaaaaca tattagcaat gtgaaatcaa gacaaaaaca caaacacaga 23880 aagaagttag acaaaaacaa aaaacactga aattacacat tttctttttc acaaatcaaa 23940 gtcaaattca cggaccttct tccctgactc attctccctg acattagaag tccaaaggga 24000 gcaagtaaag tctttatggg gaagatggta taattaagca ccaattacct agggaccaga 24060 tgctttggga tttgactgat gaaaacagat tagaagcatg gtgaatttgt tcactactgt 24120 ctttttggag gggcaacact cctggctcac ttggcatgag gtaatgtcag tctggctaca 24180 aagatttgaa tgtggggctt gagtttctaa aaggggactg attggacttc tcttagccag 24240 gatacttgga cttggtggct atatcatggc tcacagtgtc ttggaatggt ccta 24300 gttgaaattt gttgaaatta catatgaata ttcattaatg tattacttgg aactcagtga 24360 gaaggatcat cactgccaga tttcctagtt aggaaaactt accttcattc cttccagtta 24420 aatagaagac cattgtatag ttcattttgg gctaagtgga gtgtttatga aatgtgtagg 24480 gcttataggc ataactattg ctaaagaaag aaag cttgacatcc cctctgttgc 24540 ccttgtctgt ataa atttaatgtc aagggcattt ttagagaaga tgatcacagg 24600 atgattcagg tagacatgga gcaggttgtg aaaacactgg catgtttcac caatgtatta 24660 Page 22 715825 ‐ Sequence Listing.txt ccag agaaacagga ccagtagggt gtgtgtgtgt gtgtgtgtag atttatttta 24720 agagattggc tcacacaatt atggagactc gcaagttcaa aatgtgcaaa tagt 24780 aggttggaga cccagagaag agctcatgtt gcaagtcaag tccaagtccg ctgcagaatt 24840 tccctttgct tgggaggtca gtctttggct ctattaaggc attcaactga ttggagggca 24900 gtttacttta ctcagagtac taaa attttaatat catctaagaa cactctcata 24960 gaaacattta gggtaatgtt cata tctgggcacc atggcccagc caaggtgata 25020 tagatataga tatagataga tatagatata gatatagata tagatataga catagacata 25080 gatagatata gatatagata tagataatgg atatatataa tggatatata atat 25140 aattaaacat tacacctggg aagttacagc actatcttct ctggattaaa caacaacaac 25200 aaaaatactc attc atgatttgtt gagggtctgt gtagaatata gaaattatac 25260 tacaagtttg gttttcttta ggatggtgag cattttataa tata tataaagaga 25320 ggcattctct tgtaacactt agaatagtcc tgtacacata gaaggcacac agaatgtcca 25380 gtga catgagactt cataatgagt ttgaagccaa agctttgtgt agtaaaaagc 25440 catgagcagt taataaattt ccatttgatg gcagctataa atattaacca gaagactcat 25500 aactgtgttt tcaactcaca tacctgggtt ggggcagaag caatagtttc agcagctttt 25560 atttatctgc ttttaattcc ccat tgttaaattt acctgaaata attgccattt 25620 tgacaatgcc aatc atcttattgc ctggggactg attttcagat tcctgagccc 25680 agtattcaga atcctatata ttccctcaac ctatctttcc atgtgtattt tctgttgagc 25740 ttcaaactga actacctctt tgctctcaac atattctatt tgttaacttt tgttcatgtt 25800 tcta aaatgacttt tctctaattt ttttcattct ctcattcttc ttgtctttcg 25860 aggtggaact caaatgccac aacgtcaaat gccacagtat ctgctatgat cctt 25920 taca aattcctctt tcctctacca cttctttggc acatttatta agactcgcga 25980 tttctctcat ctaagtctct atgt cttactgtat gtggcctgaa ttcaggatct 26040 atgtctacag cctccccttt agcctcactc cagtatcttg caggtgggca gtcctctgta 26100 aacacttgtt aaaaaagtca aaacacattt ttcaaatcag aaagaaccta acatacaaag 26160 cctcattgtc atttttaaat ttcatcgaag agctatacat tgaatttttt gtgtgttctc 26220 Page 23 715825 ‐ Sequence Listing.txt tatagtacct agccatgtgc tggacagtgg acccacagtg gacattcagt aattagtaat 26280 agatggattt attctgtatt taacaaaatt atgc ttttagactg attg 26340 gtttgatgac acaagtttca aaagacaatg ttattgctaa tgcacattat gagggaacta 26400 tgatatattt tgaagtccaa caaatagaaa aatgaatcaa tcacgagtca gatttattga 26460 tggaattgtg ccaccatcaa gtcctaaagc attagtagtg atgttatcag tccc 26520 actctgagat tagc cagctttata ctctaaaaga tgag tatgttctgc 26580 ctggaaaagg gctcagtggt ctaggaatta ttgtttttac tttttcaaag tttataaact 26640 tggcatgact gtgcttttct gtggcttcca atctctggtg ataagttttc tcaaaatatt 26700 cctgatttat gtaa atcacaattc ataaatatca agagagactg cctacagtac 26760 catcttctga tttaaaaaca catttgaatc aatatttact tatatataat gcattctgct 26820 gaataaggaa gttctgactt gttaagctca gtatgcttcg ataagaaagc tttt 26880 tgttgggttt ttaaaatgta ttttaaggtc cttgtctctt agtt atat 26940 tgaagtgcca aact gtccagtagc tggacaagag agactcataa tatggcagtt 27000 gaagccaaag cattaagcaa aaacagttat taatattaac aggctcactg tagagagaag 27060 ccatagttgt caggggaggc agaactgccc ccca tctttgtcct tttgtctaca 27120 caggttgggg caaaagcagc agttatttga actcagcaaa cctgtgttcc atattgaagg 27180 cctgcataag tcagggacca gggatgtaat gaagaccaga catggacttt aggagcacaa 27240 agtgtagaga taaaactgca ctcataatgt aagctaatgg gaggcaggaa cgatggaagc 27300 agcaaagact cgctacagtg ggaggagtta tgagagactt cccagaagat atggcatctg 27360 agctgattct taaaagttct gtaagaggcc aacaggcaga atga aaaaatgcta 27420 ttaaacagta ataa ccgtggggat ataccagagg atgatgtgtt agggaaatgg 27480 taagtacttt gcta gatcagagaa tgttcgaggg caggtgaagg gaaaagtagg 27540 cagggttctt atatttatat cagtgatctt ggactttgtc tggggacctg caggtagctg 27600 ctaccagaat ttcttatgtc agtaagtaac atgatcagat ttgttatttt agcaagacaa 27660 cttacactat aaagtataga gaggtgtttg gagtgcactg attgaacagt agtgtggaga 27720 tgtgtttttt aataataaac caaatgagta ataacatgtc ttactcttac ataattagta 27780 Page 24 715825 ‐ ce Listing.txt agatcttgcc agcatctttg ttggatgaaa ggaagcctag tgtttatcac caaatctttt 27840 gagatgtcag tataacacaa cactgtattc cacttttgaa aacagccatc cctatagtgt 27900 gtgaagagaa tacttaaagt gcagacagac acac cgcacttctt tgtcacatgc 27960 agtcaagaaa ccagacaaga agct atgattatta gtgttggcaa gggttcagct 28020 ccagggaaaa taaatacatt gagttagtgg tggtgatgag acga atagagttgt 28080 attttccttt tcatgctgtt gcaagggaaa tgaagcttta aacataatga aattggttct 28140 tgtgaacagc aaatctgcta tttcttcact ttttatggct ttgtcaacag tgatctaagt 28200 ttac ttatttattt taaattttgt tttattttaa tagtttttgg ggaagaggtg 28260 gtttttggtt ccacgaataa gttctttagc ggtgatgtct aagattgtgg tgcacccatc 28320 acccaagcag tatacactgt acccagtgtg tagtctttta tccttcaccc cctcccaccc 28380 ttctccctga gttgccaaag tctattatat tatg actttgcatc ctcagagctt 28440 agttcccact tacaagtgag aacatacaat atttggtttt ccattcctga gttactttca 28500 gctccatccg ggttgctgca aatgccatta ttttgttcgt ttttatggct gagtagtatt 28560 ccatggtata tatatatcac attttcttta tccactcatt ggttgatagg ggct 28620 tgttccatat ttttgcaatg tgtg ctgctgtaca aatgcatgtg caagttgtgc 28680 aactgcctcc ctccctccat ctctctctct ttcctttctt ccttccttcc ttcttttctt 28740 ctttccttgt cctc cctccctccc tccctctatc tccc tccctccctc 28800 tctctctctt tctttctttc ctttctttct ttcttttctt tctctctctc tctttctttc 28860 ctctttctct agccctgcca cccaggctgg agtgtggtgc catgatctca gctcactgca 28920 acgtccaacc tctgcctccc aggttcaagc cctg tctcagcctc tgggattaca 28980 ggtgcccaca accatgccta gctacttttt ctatctttag tagagatggg gtttcatcat 29040 ctgg ctggtctcaa actcctgacc gatc cacccacctc ccaa 29100 agtgttggga ttacaagcat gagtcaccat gccccgcaca agtgtctttt tcatataatg 29160 acttcttttc cttcgagtag atacccagta gtgggattgc tgaatcgaat tcta 29220 cttttagttc tttaaggaat ctccctactg ttttccatag cggctgtact agtttacatt 29280 cccaccagta gcgtaaaagg gttccctttt cactaccttc atgccaacat ctattatttt 29340 Page 25 715825 ‐ Sequence Listing.txt tttatttttt aataatggcc attcttgcag gtgtaaggtg atatcacatt gtggttttaa 29400 tttgcatttt aatt agtgatgtca agcatttttt tccatgtttg ttgggcattc 29460 gtatatcttc ttttgagaat tgtctattca tgtcctttgc ccactttttg atgggattat 29520 ttgttttttt cttgctaatt tgtttgagtt ccttgtagat tctggatatc ttgccgattc 29580 tggatattag tactttgtca gatgcatagt ttgcgaagat tttctcccaa tcggtgggtt 29640 ttac tattattatt attattatta ttattattat tattattatt gctgtgcaga 29700 agctttttaa ttaattaggt ccaatttgtt tatttttatt tttgttgcat ttgctttggg 29760 gtttttgctc atgagttctt tgcctaagcc aatgttgaga agagtttttt tgatgttatc 29820 aatt ttaatgattt caggttctag atttacatct ttggtccatc ctgaattgat 29880 ttttatataa ggtgagggat gaggatccag tttcatcctt ctacatgggg cttgccaatt 29940 atcccagcac catttgttga ctagggtgtc ctttccccac ttcatgtttt tgtttgcttt 30000 gttgaagatc ctgt ttgc ctttatttct gggttctcta ttctgttcca 30060 ttggcctatg tgactatttt tataccagtg tgtt ttggtgaata tggccttata 30120 gtgtagtttg aaatcaggta gtgtgatgcc tccagatttg ttctttttgc ttagtcttgt 30180 tttggctatg cttt tttggttcca tataaatttt atgatttttg ttccagttct 30240 gtgaagaatg atgatggtat tttgatggga attgcattaa atttgtagat tgcttttggc 30300 agtatgttca ttttcacaat attgattcta cccatccaca agtgtgggat gtgtttccat 30360 ttgtttgtgt catctattat ttctttcagc aatattttgt agttttcctt gtagagatct 30420 tcct tcgttaagta tattcctaag tattttattt ttatttttgc agctgttgta 30480 aaaggaattg agttcttgat ttgactctca gcttggtcat tgttggtgta tgct 30540 actgatttgt gtacattgat tcct gaaactttac tgaattcatt tatcagatct 30600 aggagctttt tggaggagtc tttaggattt tctaggtata caatcatgtc gaac 30660 agtgacagtt ggacttcctc ttttctgatt tggatgcctt tatttctttc tcttgtctaa 30720 tcactctggc taggacttct agaactacgc tgaatagaag tggtgacagt gggcatgctt 30780 gtcttgttcc cagg cagaatgctt tcaacttttc cctattcagt acaatgtggg 30840 tttctcctag atggttttta ttactttgag ttatgtccct tctatgccaa ttttgttgag 30900 Page 26 715825 ‐ Sequence Listing.txt ggtttttatc ataaaagtat gctggatttt gtcaaatgct ttttctgtgt agat 30960 gatcatatga tttttgtttt taattctgtt tatgtggtgt ttta ttgactcggg 31020 tatggtaaac ctacatccct ggtatgaaac cactatatcc ctagtatgaa ttga 31080 tcatgatgtg ttatcttttt tgaaatgctg ctggattcag acta ctttgttgag 31140 gatttttgca tgtatgttca ttagggatat ttgtactttt agttttctgt tatgtccttt 31200 ccaagtttag gtattagggt gatactggct tcatagaatg atttcctctt tttctatctt 31260 tttgaatagt atcc aattcttctt taaatgtcag atagaattca gctgtgaatc 31320 catcgctctt ggactttttt tgttggcact tgttttttta ttactgtttc agtctcacta 31380 cttgttattg gtctgtccag agttcctgtt tcttcctgat ttaatgtagg agggttgtat 31440 agga atttgtccat ctcctctaga ttttctagtt tgtgtgcata taggtgttta 31500 taatagcctt gaatgatctt ttgtatttct gtgatatcgg ttgcaatatc tcgtttcatt 31560 tgag cgtattcgga tcttctctct ttaa tttcactaat ggtttttcaa 31620 tcaattttat ttatattttc aaagaaccag ctttttgttt cacttgtctt ttgcattttt 31680 gttgttgttg ttgttgtttc agtttcattt agttcttctc ttatttggtt atatcttttc 31740 ttctgctttg tttgggtttg tttttttctt gtttccctag ttccttgagg tgtgacctta 31800 gattgtctat ttgtgctctt tcagactttt tgatttaggc atttaaaact tttc 31860 gcat cacttttgtt gtatcccata ggttttgata agttttgtca tcattatcat 31920 tttgaaagaa tttttaattt tcatcttgat ttcattgttg acccaaagat cattcaagag 31980 cagattattt aatgtccatg tatttctata gttttgaagg tttcttttgg agttaatttt 32040 tatt ccgcagttgt ctgagaggat acttaatatg attttgtttt tcttaaattt 32100 attgagactc gtttagtggc ctatcatatg gtctgtcttg gagaatgttc catgtgctga 32160 tgaaaagaat gtatattcta catttttagg tagactgttc tgtaagtacc gtca 32220 atttgttcca agtt taagcccatt gtttctttgt tgactttctg tcttgatgac 32280 agtg ttgtcaatgg agtactgaaa tcccacacta ttattatgtt actgtctatc 32340 ttgtttctta ggtctagcag taattgtttt attaatttgg gagctccact gttagatgca 32400 tatatattta tgattgtgat attttcctgt aatc cttttatcat tatataatgt 32460 Page 27 715825 ‐ Sequence Listing.txt ccctctttgt cttttttttt ttccactgtt gttgctttaa agtctgtttt tata 32520 agaatagcta ctcctagact ggccgcagtg gctcacacct gtaatcccag ggga 32580 ggccaagatg ggcagatcac aaggtcagga gttctactaa aaag aaattagcca 32640 ggtgtggtgg tgtgcgcctg cagtcccagc tactcaagag gctgtggcag gagagtcact 32700 tgaacccagg aggtggaggt gagc caagattgca ccactgactc cagcttgggc 32760 aacagagcaa gactctgtca aaaaaaaaaa ccta ctca cttttagttt 32820 ccatttgtgt gaaatatctt tttccacttc tttaccttaa gtga gtccttatgt 32880 gttacgtggg tctcttgaca acagcggata cttggttgtc ggatttctct ccattctgtc 32940 attctgtatc ttttaagtgg agcatttagg ccatttgctt tcaatgttag tattgacata 33000 taaggtactg ttctattcat tatgttagct gttgcctaat actttttaaa attatgttat 33060 tgctttatag gccctgtgag atttatgctt ggtt ctgtttgggt gtatttcaag 33120 gttttgtttc aagatttaga acacccttaa gcagttcttg tagtgctgat ttggtagtgg 33180 caaattccct caacatttgt tagtctgaaa aagactatct ctccttcata tctgaagctt 33240 agttttgctg gatgcaaaat ctga caattatttt gtttaagggg gctaaagata 33300 ggaccctgct cccttctgat tggcaaggtt tctcttgaga agtctgctgt taatctgata 33360 ggtttttctt tataggttac cttt tgtctcacag ctcttgattt tttcctttgt 33420 ttta gataaactga tgactgagtg tctaggtgat tatctttgca atgaattttc 33480 caggagttct ttgagcttcc tgtatttgga tatctaggtc tccagcaagg aagt 33540 taat tattccctta aataagtttt tctaattttt agatttcact tcttcctcag 33600 gaacaccatt tattcttagg tgtt taatatagtc ccaaatttcg tggaaacttt 33660 gttcattttt aaaaattctt ttttctttgt ctgattgggt taattcaaaa gtcttatctt 33720 tgagctctga agttctttct tcttcttgtt ctagtttgtt gctgaaactt tccactgaat 33780 tttatatttc cctaagtgta tctttcattt ccagaagttg tggatgtttt tgat 33840 atctatttct ctggagaaaa tttcgttcat attttgtact agtttttaaa tttatttaaa 33900 ttgttttttg cctttttctg gtaactcctt gagtagctta ataattgacc ttctgaattc 33960 tttgtctgga aattcagaga tttcttcctg gttcggatcc attgttgtgg aactacagta 34020 Page 28 715825 ‐ Sequence Listing.txt atctttgggg gttttataga tttt gtgatattac cagaattact tttctggttc 34080 cttctcattt gggtagacta ttacttaaaa ttgtttttgt ggactgtgtt ttttttttaa 34140 tttcttattt tttctttctt aagaatcaga ctctaatgtt tattttagcc taattggagt 34200 cttggtgctt gtaggggtga agactctgta cctt agttacagaa tcttcctgca 34260 ctggttttcc ccaatgctga ttttagtagt tacatacttg gtgtgtgggt gaattctctg 34320 tctcctgtga agctggaatg gcagggatcc gctt atgtcctcct ctcatggtat 34380 acagtttatt tactggtctt ttatttactg agttgatgat ttca ggacaattgg 34440 ggaggtatcc cccggcaggc accagttgtg gctaaggcaa gtgggtagat gtaataccca 34500 atggcgagcc acag ccttgatgag tgga ggagctctca attaggtgtg 34560 ctgaaatttt gtga ggag cttcctcagc tcccctgcca agtcagaaag 34620 aaaactattc acctcacagc ctcactcctg tcctagcatt tcagctattc agatcagaca 34680 ggcatctctt ttcatctata ggaatgttgt tgttccaagt agggaggaac tgtgactctg 34740 cctctcatgc aggcctgaat ctggggtttg ctcctcttgt gggcgatact caccctggag 34800 tgttccagaa aggctgtcta caggtgtatc catgtgtgtt cctgtggggg aagccccagc 34860 tgtgtctgca gtggagtgcc agggggaaca aggactcctt ttccaaggcc cttcatggtc 34920 acagaggctg cttgcctatt ggggtatagg tgcagacttt ccctactgca cctggcactg 34980 caattgggtc tctgctgtga gaaactaccc actagcagaa agatctgaaa ctcctactat 35040 tcagattatt ttgtctcact ttcc ttgatgtggt gttctcctct ttcccctagg 35100 gatgggcttc ctgagagcca gattgcagtg actgttattg ttcttctggg tctagccacc 35160 caatggagtt accaggctct gggctggtgc tggcgaatgt ctgcaaagag accggtgatc 35220 tgatcagtct tcaggtctcc tagccatgta taccagcacc tgctctggtg gaggtgacag 35280 gatagggatg tagactctgt gagaatccct agat aggtgtagtg tgctggcttt 35340 ctcaaatgct agttatgcta gtattgaagt tgccacgtgg acagactaag gacctctggt 35400 tagccaggat gttgcaggca gtgatattag ctgttgtttt ctccttcctg atat 35460 tattgtcatg gcct gagttggttg gcctccagcc aggaggtggt gtcttttgtg 35520 tgcc aaggcagata gaaaaatacc atcaagtggg ggcaggatta ggcgggtctg 35580 Page 29 715825 ‐ Sequence Listing.txt gact cttcttgggc tagtcttgcc acagccacta tgtaggatgg ggaggatggt 35640 tttcaggctg atggggttat gttccagagg ggattatggc tgcctctgtg gcacagaata 35700 gttcaccagg gaagtggaga atagccagta gtgaaaggct tcacccagct cccacacagt 35760 tggtgagccc aatctcactc ttgcaatgct gtgttaacag caccaagttt agatccacgc 35820 ctcctgcttg tggaactcag tcttactcca ggccatacac ttccccactg agaaagcaag 35880 caaggctttc aggccacacc cctccctgtc tgcccacaag gttcctgtgc ctgc 35940 tgcagttccc attcacccac ctgt tcacgcaggt tcatgccccc tcaaaattat 36000 cacaaaattc atttggaagc cacc ttgtgccccc attc tgctggctgc 36060 tgag ggcccctgtg agatatagtc aggcatggct tccctgggtt tgagctggag 36120 agtg cctacaagac tcttcctgct gctgcttcta cttttgtgtt tcacgtggct 36180 ccctaaatct gttccagctc taggtaaggt taaatccttc tctcatgatc tggattttca 36240 ccag tgaggatatg tgtttggagg caggttttcc cccattcaca ctttgggaac 36300 tcattgcttt ttgcctgtct cacagagttt gcagcagcct gtcacttctt tcaaaggatc 36360 tgtgaattct ttccattttc ctgatatgat cctgtggtgg ttcttggaaa aaaggttcac 36420 agtctgagtc cact tcca cagg atgt tagccctgcc 36480 tgctatctgc catctttctt ctgtccccaa tccttctctt tagatagctg agataccatc 36540 ttttgtttct tctgacttgg ttctattcac tgacattcct ctctatcaag tagatttttg 36600 aactttcatg gaaatttatt cccaatttat atggaaataa ttcccaattt atatgaaaag 36660 cttataaagt gattcattaa ccaagtattt actgaggtgc taaaagtata ctctgaagca 36720 ggagtggcaa gtcctttgcc ttcatggaga ttgcattctc ttgtaaatct tacatgatgg 36780 gatt taggaataaa ggactccagc ataaaacact gacacttctg ctggagaaat 36840 attttacaaa ctatatatat tgaagcccaa actctggttt attggtaaag gagtagcact 36900 gatactagaa ttttgtgatc aacatgttgg aataagaagt cagaagactt agatctgtgt 36960 tctttttctc gcta taggttgctt taatctctga gttt cctcatctac 37020 agaataggtt agaccagatt agtggtcttc aactttggct gtatattaga attatcttac 37080 tcttgaccaa ttaggttaga aatttcgggc cacacacaat ggcttacgcc tgtaatccca 37140 Page 30 715825 ‐ Sequence Listing.txt gcattttggg atac gggcagatca caaggtcaag agatggagaa catcctggcc 37200 aagatggtga aaccccatct ctactaaaaa tacaaaaatt agctgggtgt ggtggtacac 37260 acctgtagtc ccagctactc aggaggctga ggcaggagaa gaac ctgggaggcg 37320 gaggtggcag gaga tcgtgccact gcactgcagc ctggtgacag actc 37380 cgtctcaaaa taaataaata aataaaaatt aaaattagaa atttcctggt ggagaggaaa 37440 gcagaggtat agct ctcaggtgat atatttctgt tttaaggtag gactaaaaat 37500 catgggacta cgtcagaagt tctaattata aatctatagg ttagttttct ccaggcatgg 37560 gtatagtgct taaatgcctt ttaaatttgt cata gaaaaaaaaa ggtttccggc 37620 ttctcttgaa aaatggaaat attaggcaac agttgggctt atgtttctga gtggtaaaaa 37680 ttaaacaaag taaacgagtc tccgtttcat ttgttcctgt tgccttcctg gctcttgaag 37740 tcat aaac taaactagat ggtctttaaa atctccaatt atttgaattg 37800 cttatttcca catccagaaa agagacggta aacaaactat acctttatct gtaagctagt 37860 tggtttgtga aatcaaaggg aacttaatct atgg aaaaatccca gggtccaatg 37920 gaagagaaac tccatctcat taatagcagg actccacaga ctgctatgga aaagacaccc 37980 ggct aagagggagg gaggcggaag taat tcattttctg ggcattttta 38040 atgaagcttt cccctctttc attatttctt atttgggagc tggatcatta gttgggatgt 38100 gactggcttt ccctggggag caaaaaggag attaacagag gttttgctcg cttcttcctg 38160 tgatttactg tgggaagtct cccaggttct tcccttcgct tctctgtggc cttcatcttc 38220 atggtttctt gctgtgtctc agca agtacctggg tgaaaaaggc tgagtgtgtg 38280 gttttttggc aactgcctgg cattggattt aagtgggtat atttgaatta ctagaatttt 38340 acattttata ggttcaaaat atgcacttga attctgtagg acctcttacc caaattgaat 38400 ttgt gccttgttaa attttaaaaa gtcacactat caacattatg acatatggca 38460 tatatgatgg caataataaa aataacacac ttattgtcca ctttaatgtg ccagcagtgt 38520 tccaagtgat ttgcgtaaat atcaaatttg ttccacacaa tatg aactaaatgt 38580 tattatttcc tggtttatag gtgaggaaca cagaggctca aagcagctat ttgatttctc 38640 ttatttcaaa ggaa gtgagataca ttaacctgta taaccagacc ttgttaactg 38700 Page 31 715825 ‐ Sequence g.txt tttttggtaa attccaatgt gtattgattt agac aaatcacacc atat 38760 taaatattaa ttttttcata gtccctcaag gtgcttactg gctatattgt tactgtcttt 38820 tgatgttgtt tatacatggt ggattacaga attccatgaa aaat cttgacttta 38880 tcctagccta tttcctattc ttaccccctg aaaa agttcaaaat agcgttagta 38940 agccaagcaa actacttact agccacatga acctactagc ctctctgcct cagtttcttt 39000 aaaa tggacaatac ctaactcaac tcataaggat atttctagaa tcaggtgtaa 39060 tatcaaataa aaatatattt cctttttcct tacc catgtatatc ttaggtactg 39120 atgtattcat agtgatgcag aacataaaat gtttattctt ttgcttagca acaactatcc 39180 atagagattt ttccacttta gagatttaat cccattaaag gtttttagat tgattggaca 39240 atgagaatgt ttttgtctct ctgaaactga ggctgaaagt catt ctctcacttc 39300 aaatcatact acaaggctac agtaaccaaa acagcatgtc actggcacaa aaacagacac 39360 atagacaaat ggaacagatt agagagccca gaaataatgc cacacaccta caacaatctg 39420 atctttgata acaa aaacaagaaa tggggaaagg tatt atgg 39480 ggctgggaag ctagctagcc agaa gattgaagct ggacccctcc ttacaccata 39540 taaaaaaatc aacttgagat agattaaaaa cttaaatgta aaacctaaaa ctataaaaaa 39600 ccctggaaga taacctagga aatggcattc tcgacatagg acctggcaaa gattccatga 39660 caaagatgtc atgacaaaga tgtcaaaagc aattgcaaca aaaa ttgagaaatg 39720 gaaacagatt aaactaaaga gcttctgcac agcaaaagaa ctatcaacag agtaaacagc 39780 ctacaggatg ggagaaaata tttgcaaact atacatccga caaaagtctg gtattcagaa 39840 tctataacaa acttgaacaa aagc aaaaaacaac ccaattaaaa agtgagcaaa 39900 ggacattaac agacattttt caaaggaaga catacatgtg gccaacaagc atatgaaaaa 39960 atgctcaata tcactaatca ttatggaaat gcaaatcaaa accacaatga gataccatct 40020 cacaagtcag aatggctatt accaaaaagt aaaa cagatgcctg tgaggttgta 40080 gagaaaaggg aatgcttata cactgaaaag ggaatgctta tacactgctg gtgggaatgt 40140 aaattagttc agcaattgtg gtaagcagtt tggtaatttc tcaaagaact caaagtagaa 40200 ttaccattag acccaataat cccattattg gatataaacc caaaggaata taaatcgttt 40260 Page 32 715825 ‐ Sequence g.txt taccataaag acacatgcat atgtattttc actgtggcac tataacagag acacaataac 40320 aaagacatgg aaccaaacta aatgtccttc aatagtagac tggataaaga aaatgtgata 40380 catatatacc atggaatacc atgcagccat aaaaagaaat gagatcatgt cctttgcagc 40440 aacatggatg aagctggagg ccattatcct aagtggacta acacaggaac agaaaaccaa 40500 ataccacatg ttctcattta taagtggaag ctaaacattg ggtacatatg aacacaaaga 40560 agagagcaac agacagtggg gcctacttgt gggtagaggg agggaagagg atgaggatta 40620 acaaactacc tatcagatac tatgcttatt acctgagtgg aatc tgtacaccaa 40680 acccctctga catgccattt acctatgtaa caaacctgca tagtaccccc gaacttaaaa 40740 gttaaaagaa aaaaaaatga ttaatgagcg tgataccaga acaatattat gatgcagggc 40800 tattttttgt gtgtttgcta gctgggcttg agatttgata aataagtccc attgtcctaa 40860 tccgctagtg atgatgttct agcctttgaa attcaaacta ctactactcc actttgagag 40920 agactgcatg agaattggac ccagcctggg gctttagaca ccatggttca aatcttggct 40980 cttatcattt tttagccacg tgtcatggac tcaatgtttt ccag ctccccagat 41040 tcacaggttg aagccctaac ctccaatgtg gctgaatttg agattagggc ctgtgaggag 41100 ctggtaaaag gaat tcttaaggat aggtctccaa tcctatagag ttggtgctct 41160 aaga gaca cccgagttct ttgc tatatgagga catggtgagg 41220 agtggccatc ctca gaagagagcc ctcaccagga acttaagtgt ctggcacctt 41280 gatcgtggac acct ccagaactgt gagaaataat tttttgttgt ttaaatcacc 41340 caaactgtag tattttgttg tggcagccca agccaattat tataccatgt aagcaggtta 41400 cttaaattta ctaaatatgt aagttactta aaatttcaaa tcctggttct aactttacta 41460 gctatcactt gcta acacattaca tcaa cttgccgcat gcttttgctg 41520 tgagttttaa atgaaattgc ttaagtactt tgcttatcat actgctgatc catagtaagc 41580 acttaaagtt agtttccagg aagtttggaa tggatctcac ttatgcaaat cttt 41640 gacggtgctt ctct ggaaagggtt cacctcccat tagaatagtc ctgtgactgc 41700 agtaattttg tatgttaaac ttacatgtat atctgcagaa tgttaaatct gcaaacacca 41760 tccatcaacc caaaagcaaa aaaagagtgt ttcctaatag ttaatagttg gtagcttaat 41820 Page 33 715825 ‐ Sequence Listing.txt aggaaatcta gaaaaaaaat gtttaataat gaaggctata ttaataccaa gtctcatttg 41880 agttcctgtc agtaaggaaa tagttatctt tcgttgttaa tcaatgaaga ccagttgcca 41940 taattagggc tctggtgtgt tttcttcaca tggtcttcta aatg taatatcatt 42000 tgagaggctc aaagaggatc ccatattccc aaaggtatct tagagtcctt agctgcccaa 42060 acca ttaatcatgc tttgcagatg aaaaattgaa gactccttgt atat 42120 ctgggatatg ctttcattcc taggatggac cttc aata aggaagaaaa 42180 agggacagag gtgatttata agagcagttc tactgagtga aatgtgggtc ctagcaaagg 42240 aggacacagc tgccccttgt aatagtggag ggaaggaagg aggcaggctg gctgtacttt 42300 gccctcctca accctaaacc ctatctgttt accacagtgg accttttttc tgaactctaa 42360 cctcattatt tcattcatta tccacgtaat attcattaat gttctccaag gctcttagaa 42420 taaatcttta acatttcccc aaaaagtcac aaggtctgac acctgccttc ctttttccag 42480 cttcctatca taatcctcct cagt ggccacactg atcttctttc aggttcccaa 42540 gctcagcatt tgcttttcat cccc ttacatcatg actgtcagcc tgattgtcat 42600 ttctttgggg aggccttccc tgaaccctgg aactggatca ccta tcatgtgctt 42660 tcatagcacc atgaatgtct ccttggtggc agtccccagt attc tgtgtttatc 42720 tgtatggctg tttcataaat gtttatcttc ctcccaatag tctgtcagca ctttggcagc 42780 cagttgtgtt ttgctgttga ttctacctcc agcacagaat gtctcttagt atttatggaa 42840 ggggacatga aaaaagaaaa agtccactgc atgaagattt aatccagcga cactgaggcc 42900 tgaacatcta ggga agccagcttc tagcaggaca gactggtagg gactaggtaa 42960 tgga aaaacacagg gaatgagcat cactttcttt aagactttgc ctctggcaga 43020 cccctccaag taacagattc caaagagatt gtgaatgttc tccctctggt atgcagtctc 43080 ctgtcctgtc agaaacatgg tacccagagg ccaaagctgc tgcataagca catg 43140 aaactattcc aggacaggtt tcagaagcag ggtcttaaaa atgagtatta aatctaatgt 43200 agat acatttccaa cccacatata gacaccgaat ttaacgatga aagtggaagt 43260 tactctgttg aggatttatt tgaaatgttg gttttctctt gtccatctga tacaggtcat 43320 agctctgttt ctgtcattag tttc ctca gcacagactc tctgtgagtc 43380 Page 34 715825 ‐ Sequence Listing.txt agagataagt ttaatttttc agcatggcca taggaatgat gaagtcattc ctcattaaaa 43440 tgaagctaag caaaatttaa tagtacttgt ttaagattcc ttatttactt ttctacacaa 43500 aaagagttgc aaggggaaaa caaaaacttt agctttgagt aatttcctta attcaaatat 43560 agatttaaac gtca taatatgtaa atgaactatt gcttttttca ccacaggtct 43620 gttttcaaat agataatgag attatataaa cctt atataaacat aaggttactc 43680 attattgaaa gcaattttct ttttttgttt ctggtttatt atggttaaga gtgagccttt 43740 gata tttgaaaaca aaatgtgtgt gtgc ttttgtgtgt gtgtgtggat 43800 atgtgtatct agggaggtcc tcaaattcaa aaattataat acaaggttgt aatgtcagca 43860 cttcctattg catagtttta taatggggat atatagctat gcattaaaat ttga 43920 aatggaaaat caggatgtgt tgaa ttagtaatta tattaagatc tgaatgggaa 43980 ctagcataca atgtaactta tgaa aaataaaaaa aaacagaaaa taattaatga 44040 taagttagtt tcagtattac attgataaat atttccagaa taagctataa aaaataagga 44100 ggtagattta ttattttaag gttcatacta aaagattgta atatttactt aacctttctt 44160 attt agaataagat tactgtcatc agca tctatgtaat agtgttttat 44220 ttacttttcc attaaatatt actgagataa ataaggagtc ctggtgaatg aaatataatt 44280 taataagcag agttttctta ggtgaaaact aatcatgtcc aaat gtatattgag 44340 agagaagctg aatagacaag ctccatgatt tagtcaatga tacgacttca gggaaaatgt 44400 ttttatgcct tgttggccat atcttttaat acttgcattg aaaataaaat tacatcccaa 44460 gattatgagg gttgtgaaat tttataatta gatatttaag tcctgaattg attagcagca 44520 gtataaacat agacatggat tttgggttaa atctgagaac tatttttttg aatt 44580 tgcgtgcaga tgacaatggg aaaatcaaat ctgg aaaattttca aatgggacaa 44640 atagtcatct ttctggaaat atgaaataaa ggta gtggttggac tataaacctc 44700 tttgaaggcc tctt tagctgtaat tcatgtttta tcaccattgg attttcaaaa 44760 cggaaaatac cttagaaata atttagtggg ccgggcgcgg tggctcacgc ctgtaatccc 44820 agcactttgg gaggccgagg cgggtggatc acgaggtcag gagatcgaga cggc 44880 taaaacggtg aaaccccgtc tctactaaaa atacaaaaaa ttagccgggc gtagtggtgg 44940 Page 35 715825 ‐ Sequence Listing.txt gcgcctgtag tcccagctac ttgggaggct gaggcaggag aatggcgtga acccgagagg 45000 cggagcttgc agtgagccga gcca ctgcactcca gcctgggcga cagagcgaga 45060 ctccgtctca aaaa aaaaaaaaaa aaagaaaaag aaataattta gtgttacctt 45120 gttgatatta ccaaaaaaaa aaaaaaagtg ctcagagtca cataacttga ttcagtcaga 45180 gctggtacta gatgctcagt cttctgactt ctaatttagt tcat tatctactta 45240 ctacctgctg ctgactcaga gctcctcagc tatctgcaag tggatgtgtt tattgaacat 45300 ttacgatgta catgaactgc tctcaatgcg aagctcccat ggtgaatggg agcttacttt 45360 caaa aattagtttt ctctctttgt gttctaaatg tcct ttat 45420 ctgaagcaga taag tttgtttatt ttacttttga aattttggag aattggcagt 45480 ggggtcatgc catcagaaac acatacatgc aatgcatgga tgcacggtgt gaatgagctc 45540 agat ggtagattat gggaaagaag gaagctcaga gtgg accaagtcaa 45600 gaggaaagag agaagaaaca tgtg agga aaagtaggag ggtcatgaat 45660 ccattctgca ggtgtgtgct gagtgactgg aagaaggaaa agaaccaagg aagtctctgc 45720 catgttatct tagttttgtt aagggtataa agagattgaa gagagtttaa ctaggccatc 45780 tttaacccta ggacatccct agagtccctg gcagaactaa taatctaaat tatgaatggc 45840 tgtgtgtgca cacacacagg atgcacttac taatgtctat cattatgagt atcttctgac 45900 ttctccacta caaagaaagg aagggaatgt gaccctcttt ccaggttaga agtaactagg 45960 gcatagtaac acaaatggat gaattaaact gtttaaatgg tgcactggaa tatatttatt 46020 ttggggcaaa tcatgaagaa ataaaaaagg aagagattct cttttgagaa aaagtttgtt 46080 tcctattgtc gcaa ctctgtgaac atcttaaaga taaagaatga tgta 46140 aagtgctggg atttctggtg ctgtgtgaca aagtccggtt ccttttgtct aagttagtta 46200 taataatctt taatgaaaag cagaggggtc ccatggtttg gaacaagtat ctgagtcaag 46260 agttgacaag tagaatagct gggcgcagag gctgctgtca agttgacaaa gccagaacag 46320 tacatttgga cagaaagaat ttgattttct gaat gtgatgatct tgaagaacag 46380 attttttttt tgcatgaaaa taaatcttta ttttcagtta ttacccacca gtaagagaaa 46440 gttaggttaa gggtataaag ggattgaaga ggtttctact tttgcccagt ccttattttg 46500 Page 36 715825 ‐ Sequence Listing.txt aatagccttc cactcatcca aagtcatctc ttttggaccc tcctctttta cctcttcaac 46560 ttcattctcc tcag tgtctgccac tggatgatgt cctt caggtgtttc 46620 ctcagtcaca tttgattgat ccaagtcact gcaattataa gatatttgtt tctgaatgta 46680 tttgggggac aatt catctttgac aattccccag gatc tgctacctcc 46740 acgttacagg tcctcgtgct tcaggccact gtaatgtgaa gatc tatcacttcc 46800 actataccta tcaaattcac gtttgccacg agaatcaaat ccatctcctt ggcccatttc 46860 acgtccactg ccctctcgac ctcttccaag atga ccttgaatag gtcggtcaat 46920 aatcagtcta tcaactgaaa attcgcctcc ttcacccctt tcatcaagtg gcttttcaag 46980 tcttcgttca caaggtggtc tcctttctgg tcttctatca gttattttcc cttcaccgtg 47040 aagttgttga gcaggtcttc ttccaacttg tcttattcct tttt gtgtttttta 47100 tttttcctct aggcaagctt tattctttga ttcctctatc caggaagggg gctgttggtt 47160 gcatcttacc caaatggaat gcaatgggaa ttgggagctt tgtg gaggaggagt 47220 tgtcaatctt aacaaatgac tggc gtgtggtgtc catcaatcct tgagggcttg 47280 gccatgcaca ctagggaatg gtcagaacag actcaacaga ggtctccaga gctttacaat 47340 atctacaata tcaaggttca atag acagtaagga aaaaggccat ttcctgtttc 47400 tgtccatttt tggtacagta gacagttaag gttttttctt ttgactagct tttaaaaaat 47460 tacttagaaa atggaaagct tataaacatt cataagtgaa ttgttgaatt gctaccccaa 47520 gtggtttcct tacctagtca ccacttaacc agaaatacta gaatacacgg ttcaaccaga 47580 attcaaccag aacc tgcctattgc tcaagcaatc atcagagttt ttaaaaacaa 47640 aattaagcaa aaaagacctt tccccaaata caatcattac tttgtatgac ccattcctaa 47700 gaaagctaca ttccatttca gaaaacatga ccacttaagg tacagttaaa acaaagtcgt 47760 tgccttcagg tgcttacttt ctgttttctt taaattaact gctgaaatgt tgtg 47820 ttttgtgctg tgaa aactgtaact tttaaggaca taggcctcat ctttataaag 47880 gaagaagaaa acagcaaaga ggtgtctcat ttgggaggca gaaggttatg accaatgctg 47940 gaagtcttcc tcttccttac ttgttgttca acaagatggg ttctgtggtg tcgcatgagg 48000 tgtgagttgg aaatgaaagc acac ttcttatatt catagggctt ctccccagtg 48060 Page 37 715825 ‐ Sequence Listing.txt tgggttctct ggtgcaccgt gaggctcaac ctctgtctga aggccttccc acactcatta 48120 taag gtttttctcc attatggatt ctctgatgaa ggta tgagctacat 48180 gtgaaggcct tcccacattc attacacaca aaaggaagat ctccactgtg aattctctgg 48240 tggacaaaaa ggcaagagag ctgactgaag gcttgcccac attcactgca gtcataaggt 48300 ttctctgcag tgtgaattat ctggtacata ataaggtgtg aaaaacaact aaaggttttc 48360 ccaaactcac actcatatgg cttctcacca gtatggcttc gtac aataagattt 48420 tgcg taaaggcttt gccagaatcg ttacaggcag agggcttctc cccagtgtgg 48480 atcctctggt ggacaatatg gtttgagctc ccagtaaatg ttttccgaca ctcattacat 48540 ttacagcatt tttctgtaat gtggagtttc tggtgccgag caagttgtga gctataacta 48600 ttct cacatttact acgcctaaag gttttttcta aggagaggtt tttttgatat 48660 acagtcagat ttgaactctg attgaaggct ttcccacatt ttgagcaaac ataaggtttc 48720 tgtccagtgt ggattctctg atgcacatcg agctttgcac tctgaatgaa ggccttccca 48780 cactcatgac attcaaaagg tttctccccg gtgtggattc tctgatgcac aacgaggttt 48840 gcactctgac taaatccttt cccacacatg ctacaatgta aaagactttc gcccaagctg 48900 cgga ttgttaacag tgtcagaatt aaggctgtat tttcccacag atttcttaca 48960 tttctggtct tcctcttctt tgaagctttc aggtaagtga cagtcattca ctatgactta 49020 tctgaaatct ttcctttccc tccttattct ctgcctcttt aacatgtttt ctttttcaca 49080 agcctctctt aactcaggtc gatc agctttctgg attcttccta atatgatgcg 49140 ggggttttca gcttcctcac cagt ttttggaacc agtaactgaa ggttcttggt 49200 ttcagcacct tttcttcctc ttctgatcca cctg tctgacgaaa ctcccctggg 49260 gcccagactt tgatgttctc agagtgcact tgttggctgg atgcctgatc gttt 49320 tcct cctcctcctt tttcaccttc actgggcggc atgggcctag ggccatggct 49380 aatt ctgcagtcat tgct cagcagggga acgcctatag ctgggagctg 49440 cccagcacag gtcaaacccc atctaagctt tatgtttcaa aagcttcttc ttgagtttcc 49500 tcccagggcc aagatgagta ttgcctacgt gcgcagctga gaggcccgac cagagttcac 49560 tggctctgca gcaggaggct gggggaccag gacctcagct ggca cgagaacaat 49620 Page 38 715825 ‐ Sequence Listing.txt gacccttatt ccttctttct taagcaccat ctgc gtctcctctt tcctgtcaac 49680 aacg ctggagggca gcgggttctt gctgtctttc tgggactcct gcta 49740 gctatttgcc tgccgccttg gagttggtct gggtcgcagc ctgagctgcc gctcttggcc 49800 ccagagacgc cgcccccgcc tttt ttct ctcctgcctt cagcacctcg 49860 aaggggtccg attagttgtc aaataactgg tcgaatcggt tggtgaccag gcagctgaag 49920 ccttcctgta actgcccagg catgatggtt gctcggcggc acattcctcc acggattgca 49980 gcgggctgcg ccgagccaag agcgcgtgct tcagctcttc ccagaagatc gaagaacaat 50040 ttttttgaaa tccgcctgta aggc aaggtaaatt tcaaaatgaa tttttaaagt 50100 ctctaaaatg gagttatgtt taattatgac tttatgacaa attaaaagat agttctagat 50160 attg tagaaagaag cttctcttgt tctgggaaag agtt tggaaacttg 50220 agacaagacc gtct gttttattat ttactgctaa caaactgcat tctctcactg 50280 ttcactggaa taggtgggtc cagggaactt aggaaagcct aagt gagaaaagta 50340 aattatttct tatattttta tgtatacaaa tagttgataa aggaggaagt gtagtggtgg 50400 ggtggatcat gcagattggg atacaagaga cagtataatt attcacaatt atagataagg 50460 agatctaggc ttcacatttt cacttctgga atattccact gaac agtctactgt 50520 cagc ctatcctgga gatgtccttg tggtgggaga ggacctgctt tctccttgct 50580 ctac agtttgtctc tgccagtcat gtccaagccc cttgtcttag tgcctcacaa 50640 ttcc tctgaccagg attcaggcac cttctcagaa ccttcattcc cctgacagca 50700 ggaccagcca gtctcccaga cccggggtag tgcgaagagg agagcagact ccttagaccc 50760 agagtcccag gacacttggc ctcaattccc gtgacaccta tatcacccag acaactggga 50820 aatggaggtg ctggtgccag aacaaaagca taagctgtgt ttctcaagtt tggactttac 50880 ctgggctgtt gctttatttt ctagctgttt actgattttt agaagcataa aggtttcttt 50940 ctgtgaagtt cctagggaca cttaacggag tggggacagg tattcctttt gtctttcaga 51000 aaggcatgtt tagt ctcacagtaa tttaagtctc acctcctaaa tggggtaaga 51060 gtggggagaa atatatgtgt gtatatttgt gtgtgtatat aaataatata tatatactac 51120 taatataatt aataatgtgt gtataaataa tatgtaaata acatattata ttatatgtca 51180 Page 39 715825 ‐ Sequence Listing.txt ataataaaat ttaa tatatgttat tacattaata tactatatat tataatatat 51240 aagatataat tatatattat atactattat attatatcta aata tattatatat 51300 ttatatatca ttatataatg tattacatgt attaatatat attatctata tagtaaatat 51360 atggggtgtg tatttgtgta tacacacaca cacgcacata ctgc tgct 51420 tagaatcatg ctttgcaatt attaactgct ttttcttcct tcccttcatc taatacacct 51480 gaagaatatt tcagttagcc aaaggtgaga atccgaattc atatttgtat tcccaataga 51540 tttcccgcag aatcttgggt ttca tcaataacag agat gttctattgc 51600 caat ttcg ttcatatgaa atttgacttt tggccattca aaaagcaatc 51660 agtgccttct tgttgattag cactaatcac cacaagatcc ttccaatagt aaattttcca 51720 gagcaaaatt ctaaacttac agattagttt gccgcagccc ctagccctac actgtaagga 51780 tcttgctttc catgaggtcc attgttaaat ggaaatgttc ccctggctct atgcagtgct 51840 caggtgtttc ttactcagct gaaggactaa tgaatttagt ttgaatctaa atttggagta 51900 aaaaatgcca ctcaggagag ctgcttctgt gactgcattg ccttccaacc tgcttttcca 51960 tttttcctta ttactccatg agga gtttattcct cttt ctgg 52020 ctgtaattat tttgaaaaaa attttcatta tactggacat tttggattaa gtcctccaaa 52080 ttttcttatt tgtgagagta caagtcacta tttacactat ggtaaactgc atgcaaacat 52140 ctgagtacct ttctgttcct gtcttcagct gggccagcac taagctggaa tagcctatac 52200 tttgatgttt ttctgaggaa gtacattttc cttttccctc agattcctgg tgcctggtat 52260 agcacttttt tgatttgctc ttgttctggc aataggtcaa ctggctttca tggtccttaa 52320 cgtttcaggt aaataattcc tgtg actggaagga attcaaatca actcaaggca 52380 ctat gttcaaaatg ccatgttttg agtgatttgt cctttggtta gtaactttaa 52440 aaaatatgag gactggaagg agaagctact atttgaggaa ctaatggaaa atcaagcagt 52500 ttttgatgta ctaacatata cacttatgat gcaaggagtg tgatcgttga tact 52560 tatctaaaca ttatgctctc agagcatgtg gataggtagc atagcctagt ggttaacaca 52620 catagaaaag tcagactgcc tagttcgaat ttca tcacttgcta gctatataat 52680 ctttattaaa ttagttaact ttcctgtgcc tcagtctggt tttcctgagg attaaatgat 52740 Page 40 715825 ‐ Sequence Listing.txt tttatatttg ttaagtgcct agaactgtag tgca acaagtacta tacgtctttg 52800 tttaaataat aaataaaatg acagtattgt tcatatggag aaacaggggt cttaggcagc 52860 ttaggagttt ttctaaagta tcat ttaatggcag gaacaacaat attatcactg 52920 cccagaaccc agaa ctct taagggtgat gtggggagaa atacactgat 52980 gaaaaacaat caacattatt aaagacagga tgggagagag tgggaactcg tcattcattt 53040 atctaatggc ttagtcagca agtaactaat gcctactttg ggccttgaca ctataccaac 53100 attgtgcaga aagtgattaa aatgcaaaag aacattcact taggctggga taaacaagag 53160 gtcttttgca aaatctgatg atgagcttgt tgatgttgag ttgacaaact cagg 53220 tcagtggggg tatc ataaaattcc atcccttaaa catctacagg atta 53280 ttttaagatg ctttacttct ggagatgtat gctttacttc tacttagaga ctta 53340 tgttctcatg ttctggtttt atatgtaatt gagc ttaatttgag ccaagcattt 53400 gacacagttg cccccagaag ttaactcatt tgtggattgt ataaatgcta ttgcacaaaa 53460 aagaagtata tatatacaaa tagt agaccacatc tcagttaatg gcttcaagtc 53520 tagatgaaat gttttaagag ggatattgac aaattagaga gaag catttgccag 53580 aatactggca gggcaagaaa ttatgccaaa tagtagaaag agaattagat gcctaagtgg 53640 aacatggtgt atagcccata agaatttgaa ggattgtcac tggtagaata agatgttatt 53700 cttggctgct tccagctgag gagtggtgga tgggtgacta aggcctataa gagagcaaat 53760 ataaggaaga gtttctagat attaaaatca atttccaaag aaacagcctg gcctctaagg 53820 gaaagagctt agta gatgtgttta ggtggggcca gatgaacaag ctcctgagct 53880 ctagggatta gactccttct gctggatagg aggtacaacc tccc agaggttcct 53940 tgtgttccaa gattctgtta gatt tcatgacttg gatgtcacct cccttaggtt 54000 ggttactcta aataatgtta aaagtcagtg tatgccttaa gattgggtga attgctatga 54060 cagaatgaga tttaccagag aagcagttaa gtctaagaat gaaactactg tttctaagtg 54120 aaagaggtat gaataaccta aagataatat ttttctctgt agatagaaag aatttgtatt 54180 ataagtctgt gttgggtgta ggca tcaccagaat tcaccctaac tgggtgaatt 54240 catggcagtg atcagtagaa tatgtagttt aacaatgagg ccttatcatt tctaagtagt 54300 Page 41 715825 ‐ Sequence Listing.txt ttctttttga gacggagtct caccctgtca accagagctt tgccctggaa ctcttggagt 54360 gcaacggcgc gatctcgggt ccctgcaacc tccgcctccc aggttcaaac aattctcttg 54420 actcagcctc ccgatttcta agtggagagt tatgaatggc ccaaagataa tatttttctc 54480 tatagataga aataatttgt atgctaggta tgtgttggat atatagcagg ccag 54540 aattcagcct aactcggtga attcatggca gtgaacactg caatatgtgg tttaataatg 54600 aggccttatt cttaaggcaa agctcagaaa taag agaa aggtctattg 54660 aaaagtgtct gttggccggg cgcagtggat tgta atcccagcac tttgggaggc 54720 tgaggcgggt ggatcatgag gtcaagagat tgagaccatc ctggccaaca tggtgaaacc 54780 ccgtctctac taca aaaattagct gggcatggtg gcatgcgcct gtagtcccag 54840 ctactcggga ggca ggagaatcgc ttgaaccatg gatgcagagg ttgcaatgag 54900 ctgagattgt gccactgcac ctgg tgacagcaag actttgtctc aaaaaaaaaa 54960 aaaaaaagaa aagtgtctgt ctagccaggc gtggtggttc atgcctgtaa tcctagcact 55020 ttgggaggcc aaggtgagtg gatcacttga gagt tcaaaaccag cttggccaac 55080 atggcgaaac cttatctcta ctaaaaacac aaaaaattaa caggatgtgg tggtgcacac 55140 ctataatccc agctacttgg gaggctgagg tagaagaatc gcttgaaccg aggaggcaga 55200 ggtagtagtg agccaagatt gtgccacagc actccaacct gagcaacaga acaagactca 55260 gtctctgaaa gagagagaga gatgaaagag agag aaagaaaaag agag 55320 agac agacagaaag aaagaaagaa agaaagaaag aaaaagagaa agagaaagaa 55380 agaaagaaag aaagaaagaa agaaagaaag aaagaaaaga aataaagaaa aaag 55440 tctg ccaacctgct tccacaaagg cccctcttct gattgtagaa gtgcctggtt 55500 taggatggca gtgtgctcta cctgctgtct ggtgagtagt caggattgga cttctataag 55560 acaccctctg agaggcttgc aaataccttc agaatcaggc agaggtcttt ggccagttat 55620 ttctgaataa agcatatctg cgtgtctgtc tgacctaagc ctgggaacca cgatggaaga 55680 tactgtttga acaa caacaaaaaa aggcagggaa cttaagagag aaatggattt 55740 tagtcactaa gaacacgaag aggaacattt tgataatatg tactctatac aaacagaatg 55800 cttatacaag acaatcaaag aggaatgggt agttttctaa agagtaaaac ctgtattttt 55860 Page 42 715825 ‐ Sequence Listing.txt aggaacatat atttgtttac aatatatttt ttcttttttc acccttgatt tttaactatt 55920 taataatttt ctacaacatt tttt tttttttttg cccttttttt ttttttttta 55980 aacagagtct cgctctgttg cccaggctgg agtgcaatgg cttg gctcattgca 56040 acttccgcct cctgggttta agtgattctc ctgcctcagc ctcccgagta gcttggatta 56100 taggcacctg ccaccacacc tggctaattt ttgtatttgt agtagtgacg gggtttcacc 56160 acgttggcca tctg gaactcctga cctcaaggcc agcc tcccaaagtg 56220 ctgggattac aggtgtgagc caccgcgccc agcctgccct tgatttttaa ctatccctcc 56280 tgtgaaaatt taagtctttc tgtgggttaa agggaactgg taaagagcac tggatttatg 56340 cttgggctgg aatttccctc taggtttgga tgtaatgaag gaga tttgggttta 56400 taacagaggc agatttgtga aactatagga gttgaagcct gagggtccct caga 56460 gaccccttcc agggtcctgg aaggaaccct gctaatgtgt tattatggtc atttttttta 56520 taaaaattgc aaaacataat gtgtttcagc catgactggt taagatcatt gtcttcttcc 56580 aattcaactt tccctccttt ctccttccct ttctagttgg gtggcattaa catg 56640 cgcattttgt atttgtaatt atgtattttt tttttttctt aaaaaggacc cccccaccaa 56700 attgtataag gccc taaaaacatg gatcttccac tgggtgtagg aatggaatga 56760 gtaacaattt ggaaattgcc tgtgtagcag aatcagcgaa aagtcagagt cagcagtcaa 56820 aatgtgatgg ggagagtgag agtaaattgg aatccataat cccaacagca tttgacagtg 56880 ggaaaatgga gctttttccc ccctctttag ggttcatttt aaagaattcc atgcaaagga 56940 tatcatgaat tgagaaatat acatcagatt catcagatta tttt tttttttttt 57000 gagt ctcgctctgt caccaggctg agtg gcgggatctc ggctcactgc 57060 aagctccgcc gctc acgccattct cctgcctcag cctcccgagt agctggaact 57120 gcca accaccatgc ccggctaatt ttttgtattt ttaatagaga cgcggtttca 57180 ccgtgttagc caggatggtc tgatctcctg acctcgtgat ttgcccgcct cagcctccca 57240 aagtgctggg attacaggcg tgagccaccg cgcccggctt tttgttgtgt tttt 57300 tgtttttgtt agat ggagccctgc tctgtcgccc aggctggagt gcagtggcac 57360 aatctcggct cactgcaacc tccgctccca ggttcaagtg attcccctgc ctcagcctcc 57420 Page 43 715825 ‐ Sequence Listing.txt cgagtagctg ggattacagg cacgcgccac cggc taaatttttt gttttttagt 57480 agagacaggg tttcaccatt ttggccagga tgatctccat ctcctgacct cgtgatgtgc 57540 ctgccttggc cttccaaagt gctgggatta tgag ccactgcacc tggcctaaat 57600 tctttttaaa aatagcaaat tcttaaaaat aatgcaaatt gatgatgaat tatgaaaatc 57660 atgatgagaa actcctgact gaagagagaa ggaa aatgattctc ctct 57720 ttat gtaattataa agcctttttc taaagttcct ttctgacaca ctgg 57780 ccaacagaaa ttcaaaggaa agttgagact tttgaagttc aggcaattta tatggtgttt 57840 caggtgttac tacctctaat agtctatcag cctg ataggggatg gtctctcctt 57900 tttgccttct actccatctc ttctcacaca cacttgtgat tctttttctt tttttaaaaa 57960 attttattat actt ttag tgtacatgtg cacaacgtgc aggtttgtta 58020 catatgtata catgtgccat gttggtgtgc tgcacccatt aactcgtcat ttagcgttag 58080 gtgtatctcc tatc cctcccccct ccccccaccc cacaacagtc gtgt 58140 gatgttcccc ttcctgtgtc catgtgttct cattgttcaa ttcccaccta tgagtgagaa 58200 gtgt ttggtttttt ttccttgcga tactttgctg agaatgatgg tttccagttt 58260 catccatgtc aagg acatgaactc atcattttta tggctgcata gtattccatg 58320 gtgtatatgt gccacatttg cttaatccag tctatcattg ttggacattt gggttggttc 58380 caagtctttg ctattgcgaa tagtgccaca ataaacatac gtgtgcatgt gtctttatag 58440 cagcatgatt tataatcctt tgggtatata ccccagtaat gggatggcag gttcaaatgg 58500 tatttttagt tctagatccc tgaggaatcg ccacactgac ttccacagtg gttgaactag 58560 tttacagtcc caccaacagt gtaaaagtgt tcctatttct ccacatcctc tccagcacct 58620 gttgtttcct gactttttaa tgatcgccat tccaactggt gtgagatggt atctcatagt 58680 ggttttgatt tgcatttctc tgatggccag tgatgatgag cattttttca tgtgtttttt 58740 ggctgcataa atgtcttctt ttgagaagtg cata tccctcaccc actttttgat 58800 ggggttgttt gtttttttct tgtaaatttg tttgagttca ttgtagattc tgcatattag 58860 ccctttgtca taca ttgcaaaaat tttctcccat tctgtaggtt gcctgttcac 58920 tctgatggta gtttcttttg ctgtgcagaa gctcttgagt ttaattagat cccatttgtc 58980 Page 44 715825 ‐ Sequence Listing.txt aatttttgct tttgttgcca ttgcttttgg tgttttagac atgaagtcct tgcccatgcc 59040 tatgtcctga atggtattgc ctcggttttc ttctagggtt ttcatggttt taggtctaac 59100 atgtaagtct ttaatccatc ttgaattaat ataa ggtgtaagga agggatccag 59160 cttt ccacatatgg ctagccagta ttcccagcac catttattaa atagggaatc 59220 ctttccccat ttcttgtttt tgtcaggttt gtcaaagatc ttgt agatatgcgg 59280 cattatttct gagggctccg tcca ttggtctata tatctgtttt ggtaccagta 59340 ccatgctgtt actg tagcctagta gtatagtttg aagtcaggta gcatgatgcc 59400 tccagctttg ttcttttggc ttaggattga cttagcgatg caggctcttt tttggttcca 59460 tatgaacttt aaagtagttt tttccaattc tgtgaagaaa gtcattggta gcttgatggg 59520 gatggcattg taaa tggg cagtatggcc attttcacaa tattgattct 59580 tcctacccat gagcatggaa tgttcttcca tttgtttgta tcctctttta tttccttgag 59640 cagtggtttg tagttctcct tgaagatgtc cttcacatcc cttgtaagtt ggatttctag 59700 gtattttatt ctctttgaag tgaa tgggagttca ctcatgattt ggctctctgt 59760 gttg ttggtgtata agaatgcttg tgatttttgc atattgattt tgtatcctga 59820 gactttgctg ctta tcagcttgag gagattttgg gctgagatga tggggttttc 59880 tata atcatgtcct ctgcaaacag ggacagtttg acttcctctt ttcctaattg 59940 cttt atttccttct cctgcctcat tgccctggcc agaacttcca acactatgtt 60000 gaataggagt ggtgagaaag ggcatccctg ttttgtgccc aaag ggaatgtttc 60060 cagtttttgc ccattcagta tgatattggc tgtgagtttg tcatagatag ctcttattat 60120 tttgagatat tcat tacctaattt actgagagtt tttagcatga agcattgttg 60180 aatttttaca aaggcctttt ctgcgtctat tgagataatc atgtggtttt tgtctttggt 60240 tctgtttata tgctggatta catttattga tttgcatatg ttgaaccagc cttgcatccc 60300 agggatgaag ccagcttgat catggtggat aagctttttg atgtgctgct ggattcggtt 60360 tgccagtatt ttattgagaa tttttgcatc aatgttcatc attg gtctaaaatt 60420 ctcttttttg gttgtgtctc tgccaggctt tggtatcagg atgatgctag cctcataaaa 60480 tgagttaggg aggattccct ctttttctat tgattggaat agtttcagaa ggaatggtac 60540 Page 45 715825 ‐ Sequence Listing.txt cagcttctcc ttgtacctct ggtagaattc ggctgtgaat ccatctggtc ctggactttt 60600 tttggttcgt ttca ttattgcctc aatttcagag cctgttattg gtctattcag 60660 agattcaact tggt ttagtcttgg gaggatgtat gtgtcgagga atttatccat 60720 ttcttctaga ttttctagtt tatttgcgta ttta tagtattctc tgatggtagt 60780 ttgtatttct ttgg tggtgatatc ccctttatca ttttttattg cgtctatttg 60840 attattctct cttttcttct ttattagtct catt ctatcaattt tgttgatctt 60900 aaac cagctcctgg taat ttttttgaat ggttttttgt gtctctattt 60960 ccttcagttc tgctttgatc ttagttattt ttct gctagctttt gttt 61020 gctcttgctt ttctagttct tttaattgtg atgttagggt gtcaattttg gatctttcct 61080 gctttctctg gtgggcattt agtgctataa atttccctct gcacactgct ttgaatgtgt 61140 cccagagatt ctggtatgtt gtgtctttgt tcttgttgct ttcaaagaac atctttattt 61200 ctgccttcat tttgttatgt acccagtagt cattcaggag caggttgttc agtttccatg 61260 agcg gttttgagtg agtttcttaa tcctgagttc tactttgatt gcactgtggt 61320 ctgagagaca gtttgttata atttctgttc tcttacattt gctgaggagt gctttacttc 61380 caagtatgtg gtcaattttg gaataggtgt ggtatggtgc tgaaaagaat gtatattctg 61440 ttgatttggg gtggagagtt ctgtagatgt ctattaggtc cacttggtgt agaactgagt 61500 tcaattcctg ggtatccttg ttaactttct gtctcgttga tctgtctaat gttgacattg 61560 gggtgttaaa catt attattgtgt gggagtctaa gtctcttagt acgtcactaa 61620 ggacttgctt tatgaatctg ggtgctcctg tattaggtgc atatatattt aggatagtta 61680 gctcttcttg ttgaattgat ccctttacca ttatgtaatg gcattctttg tctcatttga 61740 tctttgttgg tttaaagtct gttttatcag agactaggat tgcaacccct gcctttttct 61800 gttttccatt tgcttggtag atcttcatgc gtccctttat tttgagccta tgtgtgtctc 61860 tgcatgtgag atgggtttcc ttaatacagc acgctgatgg gtcttgactc tttatccaat 61920 ttgccagcct gtgtctttta attggagcat catt tacattcaaa gttaatatca 61980 ttatgtgtga atttgatcct gtcattatga tgtcagctgg tgct cattagttga 62040 tgcagtttct tcctagcctt gatggtcttt acaatttggc atgtttttgc agtggctggt 62100 Page 46 715825 ‐ Sequence Listing.txt accggttgtt cctttccatg gctt ccttcaggag ctcttttagg gcaggcctgg 62160 tggtgacaaa atctctcagc atttgcttgt ctgtaaagta ttttatttct ctta 62220 tgaagcttag tttggctgga attc tgggttgaaa attcttttct ttaagaatgt 62280 tgaatattgg cccccactct cttctggctt tttc tgccgagaga ttagctttta 62340 gtctgatggg cttccctttc tgggtaacct gacctttctc tctggctgcc ctgaacattt 62400 tttcctgcat ttcaactttg gtgaatctgc tgtg tcttggagtt gctcttctcg 62460 aggagtatct ttatggcgtt ttctgtattt cctgaatttg aatgttggcc tgccttgcta 62520 gattggggaa ctgg ataatatcct gcagagtgtt ttccaacttg ttct 62580 cact ttcaggtaca ccaatcagac gtagatttgg tcttttcaca tagtcccata 62640 ggag gctttgttca tttcttttta ttcttttttc tctaaacttc tcttctcgct 62700 tcatttcatt catcttccat cactgatacc ctttcttcca gttgatctca tcggctactg 62760 aggcttctgc atttgtcacg taattctcgt gccttggttt tcagctccat caggtccttt 62820 aaggacttct ctgcattggt tattctagtt atacattcat ctaatttttt ttcaaagttt 62880 ttaacttctt tgccattggc tcaaacttcc tcctgtagct cggattagtt tgatcgtctg 62940 aagccttctt ctctcaagtc atcaaagtca ttctccatcc atctttgttc cattgctggt 63000 gaggagctgc tttcctttgg aggaggagag gcactctgat ttttagagtt tccagttttt 63060 ctgctgtttt ttccccatct tggtggtttt atctaccttt ggtctttgat gacg 63120 tacagatggg tttttggtgt ggatgtcctt cctgttcatt agttttcctt ctaacagaca 63180 ggaccctcag gtcc attggagttt gctagacgtc cactccagac cctgtttgcc 63240 tgggtatcag cagcggtggc tgaagaacag cggatattgg tgaaccgcaa atgctgctgc 63300 ctgatcgttc aagt tttgtctcag aggagtaccc agccgtgtga ggtgtcagtc 63360 cacccctgct ggggggtgcc tcccagttag gctactcagg ggtcagggac ccacttgagg 63420 aggcagtctg cctgttctca gatctcaagc ctgg gagaaccact actttcttca 63480 tcag acat ttaagtctgc agaggttact gctgtctttt tgtttgtctg 63540 tgccctgccc tcagagaggg agcctacaga ggcaggcagg cctccttgag ctgtggttgg 63600 ctccacccag ttcgagcttc ctggccgctt tatttaccta atcaagtctc agcaatggtg 63660 Page 47 715825 ‐ Sequence Listing.txt ggcgcccctc ccccagcctc gctgccgcct tgcagttcaa tcttagactg ctgtgctagc 63720 aatgagcgag actccatggg cataggaccc tccgagccag gtgcgggata taatctcctg 63780 gtgtgccatt ttttaagccc attgggaaag tgcagtatta gggtgggagt attt 63840 tgcc gtctgtcacc cctttctttg actaggaaag ggaattccct gacctcttgc 63900 gcttcccagg tgaggcgatg cctcgccctg ctttggctcg cactcggtgt gctgcaccca 63960 ctgtcctgca cccactgtct ggcacacccc agtgagatga acccggtacc tcaattggta 64020 atgcagaaat cacccgtctt ctgtgtcact tatgctagga gctgtagact ggagctattc 64080 ctatttggcc atcttggctc ctcccccaga tcacacactt gtgattcttg ctggcattca 64140 cacttactct ctctttattt tttgagacag ggtctcactt tgtcatccag gctggagtgc 64200 gcca tctcagctca ctgcagcctc cacctctgga gctcaaggga ttcgagtagc 64260 taca ggcgtgtacc tccacccctg tttt gtattttttg tagagctggg 64320 gttttgccat gttgcccagg tcca acacctggga tcaagcagtc tgcccacctt 64380 ggcctcccaa agtgctgaaa ttacaggtat gagcctccat ggctgggcac ttactgtctt 64440 tttaattatc agcttgcaaa tgagaaatct gcccaaggag cctgagcttg gtgaatacaa 64500 gttcatttca gccccattgg tgagtttatg attctatgag aaga tgtattttat 64560 ttggacatgt taaaaaaaaa aaaaaagaac cgtgtgtttc ttcacaacat ccaaaataat 64620 tattttattg gtattgataa ttattattga ggaataggga agtcatgtat gttatcaacc 64680 acttcctaaa tgatacctag ttaacacgtt ggga atcgaatctg aaagtgatac 64740 ccatttagtg aagccaagca atgtagcaag agttgagaaa aacttataaa gggacctctt 64800 tgtc cataacattg tcgttaacat aaagataggt tgccagagaa agggtaactg 64860 tatggtcaat ttagccaggt ctgaactctc caag cactctcatt gggt 64920 gaagtcagag aaaagaacct ggtt tgaaaacaca gttgtaacat actgggctgt 64980 gggc tagcatttga ctctgatttt tatcttgtgc ttagaaccag cctactgttg 65040 tctctgtgca gagagagtac taagtaggta ctgaataata cttgctgtcc agcacatagc 65100 tctgtgcaga acgagcacta agtaggtact taataatgct tgctggccag cacatggatg 65160 gttt ataagtgtgt atcataaaca ctttgccttg ttgt tttcttttta 65220 Page 48 715825 ‐ Sequence Listing.txt gagttttcat actgtggaca tccttaaaaa gcccagaaaa tgtatcttta tggattgaca 65280 tgtgacttct tacatatgaa agcc aatgaaatgc tgttctttgg actgaacttt 65340 tcat gtgtgtggtg tcat taactaaaaa tatgattcat atttacctta 65400 acta caggtatcca catatccacc attaggatat tctttaaatc tggtagtttg 65460 gaagatttcc agacattgta aagagtaaat gaaa taagcatttt ccagaagagg 65520 gaggtatgaa attgtaatga ttagcctgtt gcttagtcct ggaaatgtga aatcagataa 65580 aaatgaaaaa gatgctttcc ttgcattctc ttccagaaat atgcagcctg ctgctctttt 65640 gtcttcagtg tgaccatgct gccctgagga gagcccagaa ctgtttttaa attcaaaagg 65700 acagctgctt tctgctcact caggtccact gaggcatgct ccaagacagg aaaaaggtgc 65760 ttagcggggc tctttgatag agattcaata tatgaatttt actttgagaa taaaaagctc 65820 acccactttt aaaaggttaa tcaaaagctc attgtagtgt attcttcctt tcctatgcag 65880 tttcctatgg aaatggaatc agtttaaatt ctggcctcag aacagcaata tttttcacag 65940 aggcagtcct tctgccaagt ggctctagaa gtaa tgtc aggagtatga 66000 aaaatgaaag ggatgaacac caga aattatacct cctt tactttacgg 66060 ccaggcagga agaatcctga gagaggtctt tactgaaagt tcagtattta tgaactacat 66120 actgaaaaat gaaaaacgat tcctagcact gagttgctta ccctgtcaag tttacccatt 66180 attttcaggc tgttgagcat tgtttgaaaa atcgatctga gagctaaatg agactctgtc 66240 catg gtcttgctgt tataaattca cactgggcta tttccattcc ctaagtttgc 66300 cttt cctacccttt acctctatgg tcttccatcc ggtaaatttt ctctcaccct 66360 tcctggtcta gctctatttc atcttcactt atgaaggctt ccttgttttc cttttttaga 66420 attaattgct aattcctcac tgctctctaa gcattaatac ccccatcata gccttcatca 66480 taatatgttt tgtgctgtag ttatttatgt acttacttgt ttttccccct tctttgctct 66540 ttgattaaat gcatgccaga ttta cagatgagaa aaatgagctc tgaagttcaa 66600 taacttgccc accc agttagaaga gttatggact tcactctgaa tatggtgact 66660 tttgttctag tgtgttgcct tctctagtct gaaa aaccttgtct tcttttcttt 66720 tttccttagg ttgacttatt ctatacatta gaagtttcta aattttaatc aaactgtcat 66780 Page 49 715825 ‐ Sequence Listing.txt tccagggtca tagtcagcca catgtaaatc agaatgcagt tttacataga ttcattatta 66840 ctgtgcatgg agattagaag caca agaagactta atttggaaag atatgtaacc 66900 aacttcacgt aagtgctagc ctttcattga tttctcacct ccattctata ttcctcctgg 66960 cacttgtttt aaatctgttc tactgaagtc catactctac ccccttgctc tcagccgatg 67020 atctgtttac ctgctctgag aagatttaga tcagtagttc tcaaacttta ataa 67080 aaatcacatg cagagctctt tctaacatag tttcccggga cttttcccag gaattctgat 67140 ttcagcaggt cagggtgggg aatg ctccattcta acaagctccc aggtgatggc 67200 aacacagctg gtctgaggac tacactttga gaacctctga tttaggccat cctctgcaat 67260 aggatgtctt ctccaataca tcttctctgg atatttatcc ttcctctcct agaa 67320 ttcagtcgtt ctattctcag gctgaaccct ctcaccacga atcc catctcattt 67380 catctatttc aggaccttgc ttcaacttgg ctctctttga atcttttata tcaccctctc 67440 aattgctttt tattctctac tgctttacta ataaaactgt tcctttctca ctat 67500 ttaagataca gatt gtaagcaaaa ttattttctc taagaatggt tttc 67560 agattcaact gcta ggaactaagt ttctgtaatt tgggaattgg cttgtagaga 67620 gcaaaattaa gaaaccaagt ttggccgggc acggtggctt acgcctgtaa tcccagcact 67680 gtcc gaggcaggtg gatcacgatg tcaggagatc gagaccatcc tggctaacac 67740 ggtgaaaccc cgtctctact aaaaatacaa aaaattaacc cgtg gcgggcacct 67800 gtagtcccag ctactcggga ggca ggagaatggt gtgaacccag gaggcggagc 67860 ttgcagtgag cggagatcgc gccactgcac tccagcctgg gcgacagagc gagactccgt 67920 ctcaaaaaaa aaaaaaaaaa gaaaccaaat ttaacttttt ttaatggatg tgagtggaag 67980 agactaatga gataacacaa aagagttaac ttcttacatt tctgtagtct aatacgagat 68040 agtttctcca ggaattaaca cagcacatct ggttcactga cctgagtttg tttcctggtg 68100 aggcattgca gtatcatcca tatctcaggc aaaggtactc cagcattttg tagttaagca 68160 gttggaggag gagtagggag aactgctgta ctttgaaaca tttcacagtg gactactttg 68220 cattctaatg atgttctcct tacttaagga ctttgttatg taaggatact ttgtccttct 68280 gataatcact tacacttttc ttctgtgttc atgtcacttc attaatcctg attacttgta 68340 Page 50 715825 ‐ Sequence Listing.txt atgaatcata atcttaccca cttattcttg tgtgactcat tcctacttgt attcttaata 68400 gtattttcta tgtctgataa cacattgtca tatg ctatttttaa cgtaagcgtt 68460 ggcaaaaagg tttacttaga gaaaagctct acatttaatt ccccggtgcc tcagttccca 68520 ctaa taaagattat acttagctgt cactccacgt ttcatcagta ggattaaaat 68580 gaatagagat ataa gaaa aaagataatt ataatggacc agattgagaa 68640 acaa atcaacagaa tgcc atgtcagatt tgca gtttatttac 68700 tcagtgggcc atatttcttc cttattcttt ctttttccat gatgccttcc aaaactatat 68760 cagg agggaaatac tctt ctgatatagg aagatcctac tgagagatta 68820 tattcatata tttcgtccat cggcctgtag gtggaattgt aata ctaataaagg 68880 ttattattgc ttatatatct aaaaatgctc caactgtcca aacaaagctt atactgttga 68940 tgatatttat cagtggctct gaacacttgc atatcataaa attctccctc aaaatttaac 69000 ctct ttcaggcttg tcttggtcac agtgggaact gaggacagct gctcatgttt 69060 tttgatagaa cagctcttaa catgcttttg ctcttgcctc ccactgccca acaccagctg 69120 catacacaca gtctacttgc tgtgtgcatg ctctggctcc tgtctccttt tccttcagcc 69180 tagttagcct ggttttgttt ggtttcatca tacaatgtat ctattagtaa aacttttatg 69240 aactctgatt atagtactaa actcataata aagtaatcag aacttcattt attaaaacac 69300 tgtcttgagc ttatttttta taca catgacaatt tggtaaggta ggaattttca 69360 ttcccctttt atagatggga aaactgaggt ccaggatata ggtaacattt tcaaagttaa 69420 ctcgtaagta aatggcttag ctggaatttg aacccaggtt tctgcaattc taaagcccat 69480 ccttttaact gctatgctat gcgcacaatt actgtattct tatttgctct ctgaaataca 69540 acaccttatt ctcatttcat ctgctctttc tgccctgtac acttcagttt tata 69600 gatacctgct cgtattgtga catctcaatt ttttttgtac cttggcaggg ttga 69660 tgtattggtg ttctgaactc atat gtattaatag ggaagaccta ccaaatattt 69720 catgtaatag ggattatttt gtctacctat tttatctttc tttataatgt aagtttgtag 69780 agggcagaaa ctataaattg ctcagttagg gactccacat tgagccaagc acatacatac 69840 ttgacccaga gaagtcatca ccatctttat cgccacagct aacatatggg tagtgctcac 69900 Page 51 715825 ‐ Sequence Listing.txt catctaccaa acatgtgcat ggattatttt atttactctt cacaataacc ctataaagta 69960 gactatgttg ccatccccaa aaaa ctagcccaag ttcatcgagt tactgcatga 70020 tagagtttga gtctaaccaa caccaatcta cacgtctgtc aacacagtta actatcccac 70080 acttctcagt ggaatctaga gttccactta tttcctattc cttccattct tcactatatg 70140 tcctctttgc atcc tgtttctcta cttctcactt ctat acgtatctgc 70200 tcaatcttca atcttctctg ccttaccctc tctttttcaa ttttgttctc gttctgtcct 70260 atcctgcctc cccactcttc ttacctcatt ttcctagtcc cttc tttttttcac 70320 ctttttacct cttacatatt ttaa aagtaacttc aagcttgata atagattctt 70380 caacgctctt agcaatatcg tatcctaacc ataataaaat gatagtgtgc taggtgtaaa 70440 cagaagtaga atatgaaatt aaga atctctttac tttttctatt ataa 70500 ataatgagtg actgtaacat cttggtctcc ataatttcta agtgttaaat aaaacacatt 70560 tcttttttta tttaacacac acacatccac acacacataa acttgtttta tgcattgatt 70620 gccatttatt gagcagcata tttttggaaa tgcaacaact acaaaagaat ttttaagtta 70680 ttatcataca gtgacattaa taggctcatc actttgcctt ctttccttgt tctatcatgt 70740 agagggttgc tttagagatc tatt gatatgaatt atcattgaag ttttattagt 70800 ctggatgtct catcttgggc attttgataa atttcttttg ctccaaatcc agaagttatg 70860 gccattcatc tttataaata agacttttta aaaaaggtaa agtcataaaa taaatatttc 70920 aaagcagtgt tggatatagc cagctgaata aactgccctt tctagttaac ctct 70980 aaaccttatt taaatatcct cccttttttt ctgtaaagaa gacgagaaaa aaaaacaatt 71040 gatt ctaaaagaaa atatagcaag aacattttca taagagatat ctcacataaa 71100 taaa gcaa gtatttgcac ctaaccagta gaacttagaa gagaaaacat 71160 gaaatgaact ctta tggaatggtg tggataggtt tgcattactt agatgttcac 71220 agagctctag catttactta ctgaaacact ggaatggttc atatccctgt ggtttccacc 71280 ttatttcttc cagaaggatt aggttttatg ctgccagaga ccacattgac tcttagtaat 71340 gggatcacta aattctggtt cacaattttg tgcatagaga gattgcacta atatctcaaa 71400 attgtagcta tgattataac cctggcatag aaatctgagc tatgctggca gtgtcatgct 71460 Page 52 715825 ‐ Sequence Listing.txt gtacaatcga atccacctga ttatctctgc atttgtgaca gctgggctgg ccttcattgg 71520 catatgcctc tttgctgtgc ccagggcttt gaatgcaaaa tgaaagatca gcatgatatt 71580 aggggcccat gatccataga tggagcttca caagtgaaca gcgtctcagc atgg 71640 cccccagtat cctgctttat ctttctggac tgaagttcct atgacagatt tgttgcttta 71700 aaaaagtaat tttgcagatt tttt taaaagaaat aaagattgcc ttccatttcc 71760 tactgaaagt gatatggtag tatccatctt ataattgcac aaaa ataagccaca 71820 tgtg ctgaagtata actgtggact ataaaataca gatatcatag cctataatat 71880 ggagggtagt gtgatgttat aaagccattt ttctgtgttt tacattatca taaaatttaa 71940 ctactgaagg gaaagtgaag gttttaatat ttaactaagc ctagcacttg aaca 72000 catatatttt acttggaaaa aaaggaagtt ccattttgga cactgcaaat gacagtgcca 72060 gctgttgtca taatatttct aacatccgct gaggattaat tccaggccca gcaaattcac 72120 tggatgagca gcca aagaagtaaa cactggagct tatgctgtga tattattaaa 72180 atga taca gagttggata tgtagtgaac actggattat catgcctgag 72240 gatcgtttgc tttgtgtata tctgcagaaa attgaatcct gaacttgctt tcttctgcct 72300 cttggccctc ttcctctgta gaggtatact cagaaaatgt gatctcattt aaac 72360 ttttctatta atattcatta agtactcata caatataagc tgaggaaaca aagtggtggg 72420 tgtaaaacac aggcctcatg taaagagctt actttcacta caat gtagcataat 72480 gaagcagaga tgggtttcag aggcaggtag accagaattc aaatcctact tctcctaagt 72540 atggccttgg gcccatcact taaatttctg agactcagtt tccttttcta tgaaaggtag 72600 atca tgctacagag ttctattaag aaat agat acttagacca 72660 ctacaaggta gctatttttc tagaacaggc ataccttatt gtatacattc tatgtttcta 72720 gaacaggcat accttattgt atacattcta tgaaacagaa tatggaaagt gctaaatgaa 72780 aggcacaatc agagaattcc ccaggccctc aagaaggaag gcggaatgga tgaggaagtc 72840 tgctgtccaa ggggtgggcc agagctaagg caagatttgt gggtgggcct tcactaacca 72900 ggcacaggga gagggcattc caga tgtagatctg gccaaggaat taagacagga 72960 atgcaagtgg cgttttccag gcaaaagatt aggaagtttt agatcagcct ggatatggag 73020 Page 53 715825 ‐ Sequence Listing.txt accttgaata gcaagccgac tgaggaatgc gaat gactactagc tggaataaga 73080 gataaatctc aaggcctctt ttctctttca cctctcctct tgcccacatc atggacagat 73140 agttctggct tttccttata ctctgtttct gtaagcaatt ttaagaaggc agagtgcata 73200 atggtattac ttttatgtct gcgtgtgtat tgccaccatg atag ttttgctttt 73260 caaactacta gattgtgacc ttgtaatgat ctggcaaaag gctgaatttt taaaagcagt 73320 aaatccatat agtggataat aaaa aattagggct aatactgagg aatgagaaga 73380 ttaggaaaga gataaataaa atatgggtgg tataaataaa aattaaagtg aaaatgtggg 73440 gaaaggactg cttatgattc accttacaaa atttctacct tatggggtct gttttcactg 73500 tcagttcttt ctgtgaatgc atgttcatga agatactgaa ggctgttttt ctataggcag 73560 ctggtggttt tctgctgtag gtgg ttgaggtaat cctagggagg tgatgctgaa 73620 tggggctgtg gttctacttt atgtaaggtt tgtg aaagaaagag taatttttaa 73680 aagtaattaa gtag attctgaact aacattagca aaggttgatt ataaatcaga 73740 ttttattttt actactgatt tagaaaaaat agaa atagatttgg aatggttaaa 73800 ttta gggagcacat tttggtatca cagcttaaag gtactcttaa gagaaagctt 73860 tacaaatggg gcaacctgaa aagacacatt gcat tcaaattcaa gataagaccc 73920 aaagctctgt tgccaaggta aaggttttga gagttaaatg ggaatttgga aaataatatg 73980 caaaaattga cttaaaatgt agataagcct acaagtattt acagggtgga gacatcagag 74040 aatgtaagaa tgga tcactaacag gaatgtgtaa tgggaagtca aaatctatgc 74100 tgtcaggaaa aattcatatt attggataga aactgtatta tttggtacat taaa 74160 atgaaaattg tgttttcaaa gggttacgcc tcgcagtgga tgagtgattg gggcgttttc 74220 tggtttcagt gattctgtag gcagaaaaca gtttttactg ccaagtgtgt cagtggaggt 74280 ggggagacag agaccttgct gtgttaagtg aaatctgttg cttaagaata aagctgggat 74340 ttctgtagaa tggagaagga tatt atcatattat caaaaataac tgctctttga 74400 aaagtagatt agtt tcaa gtatttattt ctgc ctaagtattt 74460 aaacactttc aggctctgat tttgtttttt ttacaaagga aacctatgcc taaaaattat 74520 tttaagtagt tatatggata catgagctac acagtttcag acctgtgtat atgactttct 74580 Page 54 715825 ‐ Sequence Listing.txt aagaggtcta tggtatccaa taataaatga ttttatgcag ggatttaaca cataatgggt 74640 catgcattat cttg ttaatgggat ctatatagag caga aaagaaagtt 74700 aattttagga tcctttaatg cctataaatt tagagcaaaa gaaatatttc taaaagttca 74760 acttttgtat acatatgccc aatcacaagt tttacagaca tttttacacg tttaggcctg 74820 aaatatttga ttccgctctt atttgtcaag atacaatata attacattag gcaa 74880 acagggcaga taagttttcc ttctttttcc tatgctatag tcatgctgca aaccctccat 74940 tttt tggctgaggt aggtctagat gtctagaggc caactaatac agttttatat 75000 aatcaacata gggaagtcat ttcagagact ggcattgagc tcttggaggg aagaaaatga 75060 aagc ttcttgggaa tatccctcac tgcagcagag tttatgtgct ctaatggatg 75120 ctccgtaaat gcttgagaga atataagtcc cataggttag catatactta attctaccta 75180 tcatggaaac ctctccatac attctatagc tgaaatattt taggagctca aaaggagtaa 75240 cagaaactaa cacc agctccaaga ttggattttt aggctttctt tctagtgtaa 75300 cacttccctt cctgttgggc catcggcaac catatcctgg ctaattagaa gtgattttca 75360 ggggaaagga agaggtcata agttcttgcc tccctatttt ccttcttgtt tagt 75420 aacttacctt aagaagtaat gaagtcctag taaaactcct aatattcaga aaccaactct 75480 cattattcaa acatgttgag atgt ctccttgcgt cctcttctgc ttaaaactcc 75540 cccagtacca tcaagcatgg atat gatagtggca gtatccagaa gacacaccat 75600 aaca aaccctggaa ataaagtatg gtataatcct aagcattcgc tcagcactct 75660 tgcttctggg aatttgctat gagtcagcca caggcatctc tgtgtacctt caagcccaga 75720 ttagcacgta gata agagagaaag tgtacttcct gaatacatct tgggtagagt 75780 aaactaatcc ttagctaggt tgatgacatc cttacccaga aagt tcagtagaga 75840 ctcttcttga aatgttgaat ttttatttct gcttgttgcc ctctatagat gagtgaaatg 75900 caatgaagat attcatggct actataaaaa tgcattagtt ctttttggtg agctacttga 75960 gagc tgta ggtagttgga attaaatttc caatttagca tcccccttag 76020 aagggtgatg gaagctccca tatcttggta tttctctttc tgagtatctg ctgtctcact 76080 gaggcaacat gctagcctcc atgttgtatt atttcacagg tatagaacta agtgacacat 76140 Page 55 715825 ‐ ce Listing.txt tgccaattcc cacgcccccc ccccattttc tttgatggag gtagattaca tttataaggt 76200 attg cttgaaggta cttgttcttt cttataagta agcaagaaag agagcagcaa 76260 gcta ggaggaagat gtgcccacac cacattcagg ccacttagtc tatctagtaa 76320 gatagagtgt ttcaggcatc aagcatgtac tgggagacat gcatacagaa aaagaacaag 76380 caatagactc ctttgagagt gacatggtag gtctgaagag tgaatgtaac tttttgtctc 76440 catcccctca gtgattcatt aattattcat tagctgtttt tttccaccag gattacaatc 76500 attttacctt tgcttgccag cctagtgggt tattaacagt ggttactcta tttatttaca 76560 cattttcctt gtgtatgtta ttcatcctgt attagttcac ccccacccct catt 76620 cttttttctt ttgtttggcc tttcatggct accatattac catgtgatca gaaaaaaaat 76680 gtgt cagaattagg caga ggat ggtaggttca tttgggttgg 76740 atagagagct gtttgaaact tgtatacaca aatt tcaagaagaa acatctgcag 76800 taaaggaaga actgcatagt ttgcagtggt ctaatggagg tgaactcagg aatctcagat 76860 gcatttagct ctacaagtct ccattataca aatgatgttg tcat ctcttgctac 76920 agattagttt tgggccatca tgaaaaactt tcctgaagat taagtcaaac ttatctatgc 76980 atgccttctt tggatacata gatccacctt tgacagctac tctgtccact aattctgtca 77040 agtaggactg agctttcttg aacacctctc cttttgttaa ggag aagaagaaaa 77100 ttaaacactc tctg cctggctgtg ccct tggtaaaaag tattacaaat 77160 tgagacggtg ccagactgct cctgtgattc atctcttctc ctgtcaagac cagttgaggc 77220 gatgcaattg ggaacctctc tagtttgtga agagacactt tatgttggaa gcaacagcat 77280 aata gtacttaggc attcaaagca attg gttcctcctg attgggtgaa 77340 caatcactgc aaattaaggt caaaagtatt gtcaaccaat tcagtgtact aggcttcttc 77400 atcatttccc atgacttgtt ctctcttagg agaaggttta gcaaattgga gcaatttttt 77460 tttttaaatc ttggtgcagc gttagtgata aaacacaaga aagtttaagg ctggatatag 77520 catgtgcatc tatatcaaga tgaagatcca tagagagatg tgcttgatct tgggatgctg 77580 gatgaaaatc caggcactgt gttgtgggag cctgatttct gaaagttggg gcatcattgt 77640 tatg acgtttataa gtgtcaggta cgtcttgtcc cacagaatac ttgttatagc 77700 Page 56 715825 ‐ Sequence Listing.txt tgttaaagga cagattgtct caac tggtacccat gccagagtag ggtatattct 77760 gacagaaaat ccatttactc gtaa tttatcccct tagttgaaac atgatcccag 77820 tgtagggcat ttacttttca cactccgttt aaatcagtgt ggtttcttcc taccttaatg 77880 aattttacct tttg tcttgcaaaa acccagggca taaa atttcaaaac 77940 aaatctttca caaggctgga actagacact ctgttgggtc acatgcaagt tatttgcaga 78000 acac tttgcatgtg aataagagaa agcaaagcac ttacaccagt attcagtgct 78060 cttggggcca ggagtgaggg gccttccatg tttgcaggac atctgtttgg gccttaagtt 78120 ctgctacagc cccaagtcct tatctcatat ctgcctggtg tttt ctgcttaaag 78180 agtcaaagac tgaaattctt atccttgttt catt cctaagttac tttagccttc 78240 acatggagcc accatgctgt ggcccacaga gtgtgctatt cacttaaact tatttatctt 78300 aacctttttg tgaaatatgg ttgcattctt tgactttcct tgcttgtcac agtttacatt 78360 aatcctggaa cttttgagtc ttaagcgcta catgatagta ctctttctaa tggtttctaa 78420 tgttacacga ctct ttcccatttc ttct ctctgttggt tttgacttta 78480 agctctctgg ctgtttcatg gcaatgatta ttggtgacag tattatctat taccaagtgt 78540 ttcttgttca cata gtttcaatgt ccttttaagc aaggattgcc aaactacagg 78600 ccacctgttt ttggagatgc catttaattg gaacactgcc atacccattc atat 78660 cacctatggc tcctttctca ctacaagggc attgtttagt agttgaaaca cagaccttat 78720 gtaccttcac ctcaaaacct agaatattta ctatctgact ctttacagaa aaagtttgct 78780 gatctctact ttgaagaaga gaaagtcgtc agatacatac aatgccaaag aactgctggc 78840 aggg atattgtaga attctgcaat tttcttaaag aatggaaaac attggaaaag 78900 agtcacctgt ttacaggtga tttgcatttc tataggtatc agaataatgt gggtgcttgt 78960 aggttgggga aggaatggca ggccttctct ctctgtcagt atcttcaggc cctgaagtca 79020 tacaatcaat ggattgcttt tcctcttcac ttttccattt tgccataatt ttgccaaggg 79080 ggaggttgga agtgggttaa tattttgcgt tagaagagca taca tcctgataat 79140 tactttatct cagatattct tagattctct ctagtgaagg ccacaccttc tctgtgcctc 79200 gcat ggcccaactg tgctacttac cttgggttcc tgctgctcag cttaaaggga 79260 Page 57 715825 ‐ Sequence Listing.txt atctctttca tatgcctaga gccttgttta tcag gtctgtacca gttgacacca 79320 agtcaaaaag cactttagac agaagcctgc tttgaaagtg ctagctagca gcaaataagt 79380 ctggcttaat ttga gtctggagat ctgattggaa gggtaaaagg gagaaaggga 79440 tgatttattt gttgactgga ttgactactt tatattagta attatgaggc aattctaccc 79500 acattatctc atttaactcc ccataaaaac cctacaaggg aggtaatata aaaa 79560 ctgagactca gagaaattaa gtaaattgca aagtccccat gctataagca ttatagtctc 79620 aaat gtcatgagct tcttctagct ttttcttcat gctcacaaaa tggttgaagg 79680 agatccaagc atcatgtttc tagttaaaaa gcag agtaaaaggc aaaaggcaaa 79740 cggacaagcc aaccaagttt gttctctttc ctagatgttc tacttggtga cttcagctta 79800 tatctcatta atgtgcatca taggattatc tctgcaaggg aacctggaaa aaat 79860 ttgtttgtgt taagctgggc accttgccac ctccataaaa tcta taggtacaga 79920 gcaggagata atcattatta ataggcaact tatagtctct gtttcaagag gtcattctgg 79980 tacctgagaa aattgacaat ctctggtcta aactcttaca ggcctctctt gccttcattt 80040 aagatgaact tgatagaata aagattattg ttgttctcta tggg tatgagacag 80100 aaca gatggaatga tttctttctg gcttccatag caaaccaaag catgtgccag 80160 gtgg caactgctac aaatacttag ccaaacgtgg ggaagagtgt tgatgctgta 80220 agtctcctag ctatgtcgag gcagcaggtg tctctgtaga cagc aatccctttg 80280 gtaagggcat ggca cttgggacta ctggattgca tcatcttggc agagaaaaat 80340 gtagcatata ctggaactct agctgggtag ggaattgaca agttgaacca caagttgact 80400 actgttcagt cagcactagc ttttatcttc cagtcaccat tggc tcttcattga 80460 tcgtccacaa gctccaggcc tgggtggtgc ctgttgtgat ataagaaggg aagagtgatg 80520 gtttccaaaa tgtgaacact catgtgtaca gttttcatgt tgataatgaa atgctagaag 80580 gggaacagct agctgatgcc tatgtctttg tccatacctg gctacccatg acaaagttgt 80640 tgtg gttgttgttt cactccaggc acaggcacag agccgcaaga gtagaaaaca 80700 agaattccat cctgcaaaag aaaactgaat cccccttgct tggtcactta gggaatcaag 80760 ttcaggaggg atgt tttctgttgc tctgtaatag gggctgaaac ttagttcaat 80820 Page 58 715825 ‐ Sequence Listing.txt tatggtgctt agctgaagca ccatgactga atcttttttt gagaaggaga aaggagaaga 80880 ttttaaaatg aaatgccata agtgtaacat agtacatata acaa acttggaaag 80940 cctgtggtgt cttggaaggt cacataaatg tgtgaaacac gccagttgca cacaggcaag 81000 catatgtccc ttctagagaa attattgcca ctgaggaatg ctggttctaa tctccaccct 81060 cccttcccct cccctccact aaaa ccagaggttt ggaattttgc gtgaataact 81120 cagtttgtta gtgttgacaa ccaggcatga cagtagctca tttggaccct ttgtccaaat 81180 caggaaacag cagcccttcc ttcatggcag ccctgtagct gtcg agtgtgggct 81240 cagc ccttactctc ctccttagct gagactttgt gccagacaca agctgcccag 81300 ctgtagacag tgggcccaga agttatcagt gttacatgag caaaacaaaa catatctacg 81360 ggccatactc agcccatgga ttattatttt gcagcttctg tagctgcggt taaaacaaag 81420 ctctggggcc agatcacctg ggtttaaatc tgggttctgc ggca aatgactcag 81480 tatttcttgg cctcagcctc ctctatctgt aaaatgaaga taaatacttg tacttactta 81540 acagggttgt tacgaggata aaatcaatac tgtggggcaa acacttagct ctacagaggg 81600 tgacacatag atgt atac caaaatcatg tgaaaatctg attttttcac 81660 acttagagaa tatacagcat ataaaatgat gggagagtgc atgtcagacc atta 81720 ttttctgctt cttggggaaa tgcttatgcc tctttggtca ctgtgaagac agagaactca 81780 aaatagtaag catcacttac tagctggcct actaaggcca caagaacaaa tgaagtaaac 81840 actctgcttg aaccactgat tttgtttgcc tgcatgaaac acttgcacag gttgacagct 81900 cgta acaatgacat cctaaaacca ttaagaaatg attaaattaa gttcagtatt 81960 atctgttgca aaagacaaag atgtgtgagg tacgttttag aataacttac aatgaaaaca 82020 actaaaaagt gaggaagttt aaagtggtga aatt gcttgagttc atcttctaca 82080 ctggctcatt atctggaagc tgggccacag agttaatact ccatctttaa tcac 82140 aggtgtttgc acctaagatg catcaggttc tgcagtaaaa atttggttcc tggcactgag 82200 acaatgctag gaggagggtg ttaacttagt actgaccata atgaaatctg tggttgactg 82260 cctg ggttgaaata aatc cagtagtatt gtag gttcaatcat 82320 attcaagtgt tcaataatga ttataaagaa agct gtcatgctta ctttaaaaca 82380 Page 59 715825 ‐ Sequence Listing.txt tatccagaaa agagaatcca aggaagtgta tttagttcta cctgcattta aattagcttt 82440 tatc attacatcaa tgtcattagg ccctaaatga tattaagagt gtctatgaga 82500 ccccaaagac aaagattgtc ccctaaactt ctattcttat ttgtttaaca tggacttggc 82560 ccagctacct taaa ttct ctagagtaag gtatctcaat ctatgcactg 82620 ttgacatttt gggccagata attctttgtt cttggggcta ccctgtgcat tttaggatgt 82680 ttagcagcat ctctggtctc tacccactag atgctagtga cttccttccc tcat 82740 gacaaccaaa aatatctgta gctg taatgtcacc tggggagaaa ctgg 82800 tgagaaacac tactctagac taagaaaagt agccagattt ttaaacacaa aagtgttttt 82860 cctcccagag gcaaaaagtg ccctagagat ggaagaattt tgaaaataag ctcttccaca 82920 aactatactg ccaaaatggt tagagaaaga tcctataatc accatgcttg acaaatggtg 82980 tttttgctaa gcctcacagc agctttgttc atgtattgtg ttaattgcaa ttaaataaac 83040 tagtctagaa gtgcgggtca tcatccagcc cattcatatc cctcctttac agtacacatc 83100 cagacttctt tcagagtttt gcttgcccat tcac atataaaaac ggtg 83160 ggagttaggg attcatagag cagagaggga cctcagctct tcatgtccac ttttcttgtt 83220 gaca aggcactgag gtccagaaag tggaatttgc agcacaaatt gctatgataa 83280 acctcagtga ttcagcccct gggatcttca atgatatagg acat ataactatta 83340 ctgagtaaaa tgtttaaaat ctta tggcaatgtt caaggtttta ggcataagta 83400 agca gagaaaaaat aaaaaatatt tttcaaattg aaggcttaaa aaattaagga 83460 taccctctat tctg gatc cagaatctta tgtttgtttg ataa 83520 cacatgactg tgtaatatca gtcaattgtg actggtaaat ttccattaat ttgcctaatc 83580 atatttagaa attatgccta ctaaataaat tatggttgga acttgaaagg aataatggct 83640 taaataagtg atttgttctt tagtcagaaa aatattctca cgctctctct cataccctca 83700 tgaagcactg tcatctccat ctagtttata attaaggcaa tgggaccaaa gtcatcctgt 83760 tggcacagga tggccatctc tgcatccaaa tttcttttac taattggaga aaaccactaa 83820 ttgtacattt taaactcaaa atgtctttat gtatatatat atttaaaata tattttatta 83880 tttttattaa tttattaatt ataattatat ttattaaaat aataattatt tttattaatt 83940 Page 60 715825 ‐ Sequence Listing.txt tatacatatg tataatttat gttttctcca tgtggctagc tgttgatcta aaggagaagg 84000 agcaaggcag tatc agtg tttaactggg agatgaggac atcactaaaa 84060 gaaaggtaca gcaggttcta ctggtatgta caagttttga ttacaaggtg tactcttgcc 84120 acctggtgtg gtgtctcagc taactttagt ttctgattac ctct gagacaactc 84180 tccagggtca ggtatagagc tccttttgcc cttggcatgt tccaaatcgc ttccttatgc 84240 tcaaccttct gagcaataca aggaaaaatt ccttgtattg gcatgttatg aaggttattg 84300 aaatacttta gcct ttgaccttgt tttgtactta gaggatgatc tcattcagaa 84360 atgggtagtg tcaaaatatg gaatgtgcta gtaaaataag cacacaattc acttaaagaa 84420 acaaaaacaa gacaagacaa acaa aacttgtttg ggatgggtga aaggcatggg 84480 gctgcaattc atcctggatt ttaaggttag aagtggttga aagaaatgtg atatttttac 84540 ctaaaccgtg gtcaactata cttttacttt ttagcaatga tgtgaatgaa gaatggcttt 84600 gaagactgtt ggtggatttg acaaatattt atcaagagcc tgctatgagt gtcaccatta 84660 taggtggtag agattccaca atgaacaaaa cagagtcctt tcttacattt ggga 84720 gaccacctct aaacaaatat atatcatgtc aggtagagat aagtgccatg aaca 84780 aaatagggta tagg tggggcagga caag gaatttatat tttatataag 84840 attgtcaggg aatgcctctc taattagatg actttttttt taatagaact cata 84900 aaaggacgag gcttatggat atctggggga agatgtcaga ggctgttata aaagttgcaa 84960 caggaaactg attaggactc ttagcagact tatatgtgct gaaa gggattggga 85020 taaaagaaaa gaggggagct ttgggaaagc attaaactgt agca ctgattggat 85080 aaaccataac attggattat gggtctgcaa atttcttaca ttttttttaa agtgtcagac 85140 ccatagccct agtaataagc gtct tttctttgag catagctgta atgaacatgt 85200 tattcttttg gagttatcct ctta tcaaactcaa gaagcaatag tttatatgca 85260 ttgcccaggt tgaatattat taatttgggt tgggaagtga tatgaccaca ttctgactga 85320 ctataggccc tagttcagtt tacctgattt tatgcccaat ttttaatgag aagggagctt 85380 gctaggccag gcaggaagaa agaaatgggg acagtgtcaa gcaggaaatg cagaagagtt 85440 gagtgtaggt aaatcccatc tttcctggct tgcc ttcacatccc tcataatgat 85500 Page 61 715825 ‐ Sequence Listing.txt cttctacctc agtcttcagt ataagcagta tgttgttcta aaggtatgaa gcca 85560 ggcaccgtgg ctcacgcctg taatcccagc actttgggag gccgaggtgg gtagatcacg 85620 aggtcaggag attgagatca tcctggccaa catgatgaaa ccccatctct actaaaaata 85680 caaaaattag ctgggagtgg tggtgcacac ctgtagtccc agctactcgg gaggctgagg 85740 caggagaatc gcttgaaccc cgga ggttgcagtg agccgagatc gcaccactgc 85800 actccagcct gagaacggag cgagattccg tctcaaaata aaataaaata aagt 85860 aaaggtatga agtcttttcc aagctaaggc aagaatgctg aaacctcaat catagcactt 85920 ttccaaaaga gtcttacctt atattctgga tctcttcatt atctcaagag gggcttcttt 85980 ctctttaaat gtgaaaagaa gagaggcatc agctagccct attagcccag ggctaagaat 86040 tgctccagat ttttgaatgc ttaaccttaa acaaagtcac cagt tggc 86100 tcccctgttt acag gtcagatttt aactacgtgc ggct gtct 86160 tcggagttgt taaacatgca gagc tgttgactgt tttt ttct 86220 tttt gccttataat ttacttttat tttaaatcta ttatactttg aactgttgac 86280 tgttagagaa agcagtactg gcttaggatc agcagagaat atggttgaat tctatttctt 86340 aaactgagga gaatttctgt ttgagcccag tccaagtcat tacttgagca attttttgcg 86400 cattttgctg tgtt tatttttttt ttgcttttac aagtaatttt ttttaaaaaa 86460 gttatcatac actcagcaaa cattttttga gcacgtacac aatgcccagc cctgtgccat 86520 gcatgttcaa aaaaaaaaat aggtaacatt atatctgtgc ttgtgaaatt aatacatttg 86580 ttagaaagat aagacttcaa tcagtaaagc aatccaagaa ggaacaagta caaatccagg 86640 aaggagacat tagctcagtg gaaagagtcc actgaggtag gtagacttgg gtttgagtca 86700 gaagcaagag attgcttttg tgagatttcg cttatcctgt gtgggcctca gcttcctgtt 86760 atgtaaaatg ggataatagt acctattaca ttgtcacatt ctgt gatgacttga 86820 taatatttat agca accagtataa tgcgtgctca tagtaagcac ttattatatt 86880 attattattt attggacata taattagaag gtctgggtta taatcttgat tctacaatta 86940 tttagttttg gtaagtcact taactttatc ataccattca tgcatattac ctataaagtg 87000 aaaggaacag aggttctaca atttatctcc caaattccat ggtattttga accaaaatgt 87060 Page 62 715825 ‐ Sequence Listing.txt attgaataag tatttgatgt ttgcttcccc ttcttgttag tgatatttac aatagcaata 87120 aaacatcaat atttatttag gacttgctct ggagccacga gccgtggtgt gttcttgaca 87180 ttatgttatt atgc tgcatactca gtgagacaga taaccttgtc ttgtttccta 87240 gatcctaggc catattttat ccagtttaat atttctgaaa tcagaatgta ttatgtagta 87300 ttatgtagtt aataaatata tttaatgtgg aatttttttc ccaaaagccc tttctaagtg 87360 agatggaccc tcttatgatt taatgaggat gtcttccaag ggaaataaat attttttcta 87420 tgat ggtaaagttg aagcatagag aggataattt acatgaccaa gattaatgaa 87480 aaag caaattcagg acttgaactt aggtttgttt tatttaacaa tgctcaccct 87540 accgtacttc ttgggagcaa aaaatttaaa aagtttctaa catatattca ttagttcttt 87600 ccatttttta tagcaaaata tatttgatct gtctctagaa tcaatgatag attcactatt 87660 tgttaacttt taacaggaat atattttagt agcc tgactttata ggctatgtac 87720 ccagtacatg aaaatatata gtagcctcag tttaatgttg atgtttattt gatgtcgaca 87780 gtga cactggtcaa gcgtatcctt ttagataaga gcctattaga attatatatt 87840 ccctgtagaa cctt gaccatagta catttaacag cagatttttc tcagactttc 87900 aaaatcctga aagtctgggt cattacaaga aaacaaggat gtggtcataa acagttgatt 87960 attaagcaaa ttcattgaaa attaacagca gtattctttg acctcactct ttatagccaa 88020 actgctaatc ttgggtaaat tataagatta tattactaat acat ttagcacaaa 88080 ttagctatca aatgggtcag ttgttactgt tggaaactta tgaaaataca ttaaagttct 88140 tcccatttcc tgtatgtttc tttctctgac tctt agaggctttt attaggctgg 88200 gagaacttcc atct aatgactagt tgaataattg tttatgatat aaaatcagct 88260 ttgttgtcag aatgattaca gggt catagttaat agaaaaatat ttcagtgaag 88320 gttaccatta gtcgttgtaa gtatcccttg attcaagaag tgaaactttt attgaaaaaa 88380 ctatttgcag agctggagcc ggcc tttctgaagt ttttaaaatt aagaaatcct 88440 atctctactt ttaacaagac atgaatgtta gtatattcac ccagactaaa tgaatgaatg 88500 aatgatcaca atgc tttg atttccttcc gttc actggactag 88560 cagcttcagt actcaagtgc gattgtaaaa ttacacatgg tggaattcaa aatggtgtac 88620 Page 63 715825 ‐ ce Listing.txt atcagtcagg aaag acacacaatc agaa gtttcaagag acttcaaggg 88680 taca tggg taggattaaa gtagctagca aggaatgctg agtcactcgg 88740 accctagctg ccatgagaag ctattatctc acct ggagctgcag aagaaggaaa 88800 ccgtgttact ctagtcctga gagggccgga gccatggagg aggggtcttg tgacagaagc 88860 taaagttctg gagagacata ggctaggcca gagcatagga atgtggggaa gacatccctg 88920 acctctctgt caaccttcta atctccattg ttcaaaccca gtaggaagtt atccagcatt 88980 gagcctggag cccg cagcagtcag cctcctgagt gcagagcaga ggaagacctg 89040 gaatggatat ggag gagggccaaa cagagagtaa ctagtccaga tgggaaatgc 89100 tattttagac ctcatacact gccaaaaaag aatggcatat aatc caggaccttg 89160 acctcatttg atcttggatt tgcatccatt ttctgatact ttcttccaaa tactcttgta 89220 agcatctgac agcagccagg gctg gtcagttcag cctgtcccag cttcattgct 89280 gaggtacata tgtggttaag gagctgagag aactggtctg atagctcacc ggcc 89340 tttcccaagg aaaataaaat aaagagaaaa ttcattgaga atctgtccag aaaggacagt 89400 aagtaggcat ggaatcatag tagtaaggaa gcatggagga tgca taaaaatgac 89460 ttgtgatatt tttgaagcta tatgataatg ttctgaccca cactcttgcc agcctctgca 89520 atcttctgga ggcttcatat gaaagcagga ttggtatgct gtttattata aatagtgaga 89580 cctgagagat gattactgtc agcataaatg gatattacac attgcaccta tctcccagca 89640 ggaagtttgt ttgtttgttt gtttgtttta gacggagtct tgctctgtcg cccaggctgg 89700 agtgcagtgg cacgatctcg gctcactgca agctgcgcct cccgagttca cgccattctc 89760 ctgcctcagc ctgccaagta gctaggacta caagcgcccg ccaccacgcc cggctaattt 89820 tttgtatttt ttagtagaga cggggtttca ctgtgttggc caggatggtc tcct 89880 gaccttgtga tccacccggc tcggcctccc aaagtgctgg gattacaggc gtgagccacc 89940 gcgcccaacc agaagtttgt gtttgatgtc actgttgttt caccaattta aaagaaaatg 90000 aatattttta aaggaaaaga aaaaagttat cacactatgt gatgaaattt gtatctatgg 90060 attt gctacttggt aaataattaa agcctgtact ggttaccttt cctttagcag 90120 ctgacaacaa atcc tcacctcaca ccttatacac tttactccat ggttcatttt 90180 Page 64 715825 ‐ Sequence Listing.txt cagtattatt ttct cttgcttcat catactattg cctggcaaaa ttccaaccca 90240 gatttaatcc tgctttccat ctataccctg cctacacctg agagttcaat gttactgtgg 90300 aaaatgcaca ctgtggtgac ttgtttcact gcat gggccctaac ctcactgagc 90360 catttattag taatgattgg caactctcca tatttcttga atccactcac tttcctagtc 90420 acaa ctatgtgaca actcctctat cctcaagcct ccaacaatta cttctcatac 90480 cctaactctg cgcagataac cttttttcct atttcactgc aaaaagccca gaagtaatca 90540 aaagtgaatc tacaagcttc caccaccaca tctactcctc ccagtctcag tgaccatatg 90600 gtttgccttc cttctgttaa cagagagctt ctatcaaaga tgaacctctc cacttggcac 90660 tttatttccc tcttgcatat tcaaggacat tagctcagca attttctttc tttctccttt 90720 cttgcattat ttattttctc cctccaccag aagttgtcac cccaacttct attagaatga 90780 cttaggaagt gcaggcctca aacctttttt tttttttttt ctac ctctattagc 90840 actccctgct cctattttag gaatccaggc tttaacgcta acagttacaa attaagccac 90900 aagctttgta agtatttgcc tgtgctctag gtgg gtttttggaa aatcagtatc 90960 tgatgggcat ttgaatacat ttgctcttgt ggctttaaac aatgtctgta caataaaaac 91020 ttgagaattt atctcctctg aattctagac attc aactacctag ctggcatttc 91080 cacttgcatg ccttaaaggc cctcaatctt atctgtactg aatcgatcac ccccctaact 91140 tccg tcagttatcc ccattgcagt tggtgacatt tttg gttgcttggg 91200 ttaaaaaatg ttggagtccc ccttgactcc tttctttctc tcatttccca aagccaattc 91260 tttggcaaat agtaaccatt tatcacattt tccactgcta ctgttctggt ccaagccacc 91320 atcctcattc acttggatta ttgcaaagac ctttacctgt tctatatgct tttatatttg 91380 ctcatttttc tcccttcacc ttgc tttcagcaca gtatatcatc tcatgcatct 91440 actcaaagcc ttctaatgcc ttcccatttc atgatggcct ccct ttgtgatctg 91500 gttccctgaa atccttgact tcatttgggc agatgtttct gctataacgc tatttatgtg 91560 aaaa ctttttggtc atgt aaaa ataacaggtc ttatggtaaa 91620 attacgattg gaatagaaca ctcatatctt cata aaaaactgta gcaataacca 91680 aagcaataat agataccttg ggagataaca ggaaggcagg cagctcagat tgactgaagg 91740 Page 65 715825 ‐ Sequence Listing.txt cgactcaagg aatattaaaa atgcacaaaa acagtagcat ggagatgccg gctggggagc 91800 tgagatgaga cagatgaatg gagctctgag ccagagggcc taccacaaaa gtggtcatag 91860 gaagaagttc agcctgcctt atag ctttgcctgg aggg cgtatttctt 91920 gggagacacc tctgggtgca catc tttaattccc ttaagagagc tgaaatcact 91980 gcagtctgtg cagcagccaa ggat ttttcctttc ctgctaaggt tataattctg 92040 ttcttgctat tcttactcct cttgcctaag aaaaatcttg tgta atat 92100 tatcccacta tttaccagta gcatatgagc tgcttgctgt tacagaaaca gtaa 92160 tagaacagac tgcactcctt gggtcatctt tgttatttcc catgtgtcag gtgagcaccc 92220 accttgtgac ttttgctact ggtctttccc gaat cctc cagaagtcct 92280 tttc ttcttctatt tcagttcttt atttaaaaat atttttcata gtttgaacct 92340 ctctaaccag ctgatttaaa agaacaacac caccccaaca acgttctcta ctttacatca 92400 tagtttaatt ttctccatag tatttatcat catctgatat attataatac tcatgtattg 92460 gctgaaccac aagt attaagatcc gtgagggcaa gacttgtggg tttttaaact 92520 tgttttcctc ctttgttttt ctctattata tctttagtgt ctggaataag gttcagcaca 92580 tacaaggcat ttactaaatg ttgaatgaat gaatgaatga agctcaagct ccatctacaa 92640 acagtcctct gttttttgtt ttttgtttgt ttgtttgttt tttgtttttg ttagctgtta 92700 tctggctgtt ttttattaga taataatttg tcttccttta cttactgatt ttgtttatgt 92760 gtttgcaggt gtgtgtgtgt gtgtttgtgt gaaagaggag aatgactttt atcaaacctg 92820 tgtc ttccttagga tgcatcagag tttcatgctg ttcacactac ccttcggggt 92880 acat ttaaagtctt aatatttcag agtc ttaatatttc tggcctggaa 92940 aaatactgtg atatgggttg aattcatctt tttgcacccc tctatcatca taaccactcc 93000 ctgctcccat tctaggaatc caagctctta tgctaacaat taaaaattaa gtccacagac 93060 tgcagataga ccctacgctt gagctgccgg tgggttgctg aaaaattaat atttgatgga 93120 aatttgaatt aattgcctct ttacccccta ccaatccctg tgtatggtca aaaaatagga 93180 cattccaata ctccacagtg atggccacag tgctggtttg tgctgatgtt ataaaggagc 93240 aggaagatgg taatgaactc cctctggtgc tggacaaggc ttcacaaggg tgctgatgaa 93300 Page 66 715825 ‐ ce Listing.txt aacaatgtga gaaaatggac tcaggggttc tcaaggcaga gaatggtggg gggatccagg 93360 aatccacata ttcaaagaca caaagaagta tctg aggtgttcag gtga 93420 ttcattaggt atggggctgg gggtggggca cagggtaggc agaggagaga gcagtaggtg 93480 tatatgccat gaagattttg gaatcgatcc aactatacag ctatcaaagg tttttggtga 93540 tacaaccaga ttcgtcttct cactccttac ctttctcacc tgatccctcc ctggcttttc 93600 caaactgtca actataaggc tgtgtgacca gagagcatgc ccctgtcccc agtactcaga 93660 taagtgcctg acatatatat atatacatag acaacctact tgtttatgtg tctgaacaaa 93720 atat tcatttctgc attttctttt cagcaatgct tacactgtct tcaaatcctt 93780 tagggcccta cacttgacta tcaggctgcc tattgaaaac taactttaca tcat 93840 tggttaccat gatggcacaa attc tttt tttttttttt taactagaat 93900 tgaaagcttt ttct ctttttctgg ttcc cttctaccag atctgattca 93960 tggtgcaact tttggtggca tcacccctta atccagcaac atttttgtat accctgaggt 94020 tattactttg atgtcctgaa cttatggctc tgggggatat aaag gggtcagaga 94080 aataaggttg aattagagag attcttagaa gatt aaaacactat cccctctgat 94140 ctgagtccca gctctgccat tgacaggttg tgtatcatta gcaatagcaa gctacttcac 94200 atttctgaat ctcagttgat tgagcaaaat ttagataatc aaagactact ggagatgtga 94260 tgctttgaca caaagaaatc tacctctttg gtgaaatttc aattgtgtag gagcagttat 94320 ttgggagaaa agtgccctct caccttctta aatcatctcc tata ataggaaata 94380 cgcagctttt gctgagaacc caaatgacat tgtggattat ccagctctag tcttctctct 94440 taga ggccggttat ctttgtcact tcacagctca ttagcagccc cactcagggc 94500 catggagagg aaatagatga gatgaagctt aaatatgtca cattggttat ttcttagcag 94560 ctctgataaa aggcttagca ggggccaggc gcggtactgt acgtctgtaa tcccagcact 94620 ttgggaggcc gaggtgggcc gatcacctga ggagttccag cccagcctga ccaacatgga 94680 ttgt cgctactgaa aatacaaaat tagccaggcg tggtggtgca tgcctgtaat 94740 cccagctact gctg aggcaggaga atcgcttgaa ctcgggaggc ggaggttgtg 94800 gtgagccaag atcgcgccat tgcactccag tctgggcaac aaaagcaaaa ctccgtctca 94860 Page 67 715825 ‐ Sequence Listing.txt aaaaaaaaaa gcttcagcag gtta aaactcaaat aaagaggtct gaggattatc 94920 tgtgatgtta gctcatgtgt gttaccttcc tgtcttccct tctttgttct tagg 94980 gattagttga ctgcaaacat taatgggtta aatataaaaa tgactgcaaa cattaatggg 95040 ttaaatataa aaaatctttt ctatcctgaa ggtctttgaa aaaatgattt tattacttac 95100 tggaaaagaa aaataaaaca aagcttgctt cacccagaat ttattttttc ttctagttaa 95160 aatgagcaac ttctttaacc agaactgacc ttgaagacaa atggctaaaa taaaacattt 95220 gctgaattca ctgggcgcat cttacaagta ggat tctgcattga ctacctacaa 95280 gtgccttctg ggtgcaagtc cacaggcaag atttgttctg caaatcttcc atgaccaagg 95340 tcacctcttt ggattggcag acccagggag tccatattgg gaagataaat tcacacttca 95400 ccccttgttg agatctccag ccttgctcct ctgataacca ggtctctctt ctgtcctatt 95460 ataatttatg acctttgaaa agttacttat atctggggct attcaaactc ccagctatct 95520 atgaccatat gcataaatgg ttctagattt aaaaaaaaaa agaagctatt tatt 95580 gggataccct ataaccaata taaatgggta attcagcaga accagatgct gaga 95640 aatagatgtg gacaattggg gcagggccta atcg gaggcaaaga cagtgactag 95700 agct ctgataaggt aatgcccagg cctgtgcttg gaattctgcc acagtgggga 95760 tggg ggtctgtagt cattgcaggg gagg atagaaagaa aagattgtgt 95820 gaaggtcagt ggaaggtccc ccatttcatt gctaagagaa atgc acgttttcct 95880 gtgtttagtc tcacacataa ttgtaccttt aagaactgat cacacactgc ctgg 95940 cagtttttgg catctcagat gaggaagagt gatgggcgac aggtgatggt gacaactatt 96000 aataagatct gaaagtaaac agtctcatga aaggtggcca ggagagggca gtcacctttt 96060 atcaggagca cagactgaat ttgcaaaggg tacttaagct acaagactat aaagcatgat 96120 ttaa ccaaaatgca gtgtcttgag catagtagac tcttagtgta tgtttgctaa 96180 ctta gctgctgctg ttccccagag ctcatcagag ttccatagaa acctggtccc 96240 ttccagaaaa ccaaagaatg actaaagaaa agtgattgca aatccagaaa gcagctttgc 96300 cttactggtt ggtaacagca ggattttctt ttccttgtag tttattttgg ctag 96360 tgtctctttc atgaagacag ctactattta ttgt taacatgttt ttcctttttc 96420 Page 68 715825 ‐ Sequence Listing.txt atctcccaat atactctctt cctgtcgtta aacacagtca atttaccaat ggaatctgct 96480 gctc ctgcattttc tttttccaca gatgggatta atgccattat gttctatgtc 96540 atccacatag tcttggcttc taggcaccaa ggtgttgttc tagaggaaag aagagtaatg 96600 gtcgacacag gcaggctgag ccta atgatttcat gcatttagtg gtaattctta 96660 attaagatcc caattttatt ctgttggatt ataa cccgctgaaa atcattcttg 96720 aattaacact gggtggatat aaaagcagaa agccaaggac tttgcactgt tctcagctgt 96780 agctgtttat ttagctggag aaaatttagt gggtggtcca accttcataa ccaggaagaa 96840 taaaatagag gtgtaaaggc cttggtggaa ggagggcagt agcaaccttt ccatttcttc 96900 agttttatcg cagcctatga ttcc ttaggtatgt tgta ggagctagta 96960 ttttaacatt tgctccatca ttgg tttaaatcta agaataagcc cactgaaaac 97020 tattcctaat ttgtgaaacg aataacaata gtta atagaaacaa agacttcatt 97080 gttt ttagaggggg cacagagaat acat aataagttag atttttgttg 97140 ttttcttttt cttagttctt tgtagtcttt ataatctcta attggcattt gctcctgact 97200 tttctcagtg tacttccaca tggaagagac aaaagtctca aagctggtgt agaaaaaccc 97260 ttaataaatt gcccattaat tagccacctt gatttccacc tttaaagcag ttaattgaag 97320 taagaatttg ttagattttt ctcaagcata gcagaaatta attt cttaggtgtc 97380 attgctactt gcctacttaa accaccagtt catctttatc actt aagccaaaag 97440 tcacattaga ggcaatatgg cacagtgatt gtggaccccg gagtcaggtg ttga 97500 aatcctggct tggctacttc ccagctatgt gatcctgggc ttcagggttc ccttttgcaa 97560 catgacatga ttgctgagct gcttcttagg gttgtgtgtg gctccggtaa gataatacag 97620 gaaaagagct gaaagcagta tctgaccctg gagagaaagt agggaagaga caatagagga 97680 aagaggacaa ggaagtggga gatgaagaga aagttcaaga aggaaagtgg aagaatctca 97740 aatagaaagt taattttcag tttttcctga atat atagacatct tcatgtggct 97800 ttggagagcc ccca tcagcaagac ggttggaaat gaaa cagaagtgta 97860 gacctatgtg acttatgtcc tggccagttg cctcatgtcc tctgtggtca ggttgatctc 97920 tactggcact gtcaaaagat tttttatgga cagctggttg gggtaaactt tgaaacctga 97980 Page 69 715825 ‐ Sequence Listing.txt ttgtttgcac ttgagtgcca gagtgtgtaa ttatttaccg gtgttcacta aggatgtcag 98040 tttt tagggggaga aaaaacttaa atttaaaatt tggaggcatc tttttcagtc 98100 tgcctgccct ggtgtttgtt ataacactta gtttggcatg taacagctga agctactggt 98160 taaatcatta agcatttatt attttaaaac tcctcttctc aaagcaaaaa ataactatca 98220 tgttgaagtt ctttcctcta agaatgacat ttactgtgag ttttatacca atggactaat 98280 tggagggttg agaaaataaa ttttggaaag acaacaataa cttcagaatt ttccttggat 98340 ttcc tttttaaaac ctgaactgag ctttatcaaa acagtaactg aactttgaaa 98400 cgaaacaaga gtgctgaatt gaaagctcca ggaaggcagg gatgtgtctg tgttgtttat 98460 aacc tctgggccta aatcagtacc tatcccatgg taggcactcg gtaaatactg 98520 aaggaatgag tacagtatga aaattagcat ggctgatcct tggaaaaaat ataagtcaaa 98580 agggaatagc atgcatgtgt aactaaaaca tcagtccaca tgcttgaaat gtcatcactt 98640 ttttatggtc aggacctgtt tttttctgct aaag aagaaaattg taatgtgaaa 98700 agaa gtgaagtatt tggtattcat gtgttttgac atctgcagta agtttaaaat 98760 aaatttctaa atcttattgt attgaaattg tatgagtttc ttaagtggta ttattcattc 98820 agacttaaag tagg ttgctgtcac tcatagtgga cttttttttt tttggcatta 98880 ttaaaacaac atgtcttctg ggtgttgtct acaa aagcttgcgt gttttctctt 98940 gatgctgtgc cctgtctgtt gccattgagg ggtctaagga ccaaatgagg ttcc 99000 ttcctgatat tcttttgacc gaat ggtc cattcacaca actaagcggc 99060 tcagttctct cagttccctg gtcttctcat attagattgt tatctatgag cttgaagttt 99120 agacatgaaa aagaatggtt gtaatcctct tccttctctc accctcttcc ctttttttct 99180 agcc ttttgaattc atgattctaa taattaatat atattattat ataatatagt 99240 atatattcat aataatgatt aatgatagta ttaataattc tgtgtgtgtg tgggcagcta 99300 ctcatacaga ggaaaacaga ttgattagtg acat taatttcata acttcttatt 99360 aaaagagttt gtgtgtgtgt tgttggttgt ttgttccctt tgcaactcaa catggtcttc 99420 ttgaggtgta acat atgcttagga aacagagcct tcttttctcc ttttggtatg 99480 gaagacatat agaa tgaaggaact ctct agccagggct ctgcaaaaat 99540 Page 70 715825 ‐ Sequence Listing.txt agtactggta gagaaaaagc tctaaaagaa gtaaaagttt atagtgcttt ctcctggcag 99600 agttaacctc atcttcatca gcttttcccc tgcctcagag aggcagtttt ggaatgacca 99660 aagcagagtg cccaacctct ctgttcagag ttagcgagca tcac tctctctctc 99720 tgcctcagta tgagtggaat attgcatgac catttctgat ttctgccatg agcgcactcg 99780 gcctagatga ataaatcctc cttgaagaag gcggggcatt ttggcattca caagaaacca 99840 tgttgatatc tccc actggagaaa tgtggcaaag tgagaaagac tcactctttg 99900 ggactccaaa aatgtaaaca caagtaagca ctga agaagtcact tgaaatagaa 99960 aaaaaaagtg ttaaactctc tgttagtcat gtgacttttt cttggtattc gagagccagg 100020 ttgt ggtctaatct ggaaagagtc cgct gtgtcacctt ggcaaattgg 100080 ttgatctccc tgtgctggag tgtttagtcc agctgctgga tgggatgaaa gcaagacctc 100140 actgaaacca gatgctgtct ctctgaaaag atttcagcaa taaataatat cgtatatact 100200 ctgg cagcaaatac tgaactgcta tctg ttttcacttg aatt 100260 tctggaaata tctcctttgg gcttgaattt ttccatgctt gtcttcagcc caaaactttt 100320 tggaaagttt aatt agct gtttttcctg aattatggga gaataagggc 100380 aatgcattgt ttttcagctc ataaattctc atttttccca ctca gaaaaatagc 100440 tgctacattt ttta gaactagtaa aagaatcttg taaa gaatactggc 100500 agaagacaaa tttaagtctc tcagtatttc actt taaacatgac tgcacacaat 100560 cagggcacac ataaaaagct ctgatgtagt tttatagatg gccaaagaga agattctgca 100620 aattctctca gtaactcatc ccaagttacc aagaggcaac tttagctacc atcagttgtt 100680 acctttctca accacttgct ctgtctgtgg atctgatttc taaaaaaatg tcatggttat 100740 atgttggcat tgacccctta tctacatttt aaataaagtt gaccatttct tttaggtagc 100800 cttcatgtgt gatgacctca gtcatatctg ctgacctact agactcaaaa ttcctttaca 100860 gcagggccta ggtctgtcta cctcaccatt gacactgtag tgctcagcag ggtatgacac 100920 atgtagtaaa aactgattgt tgaatgaatt aaatgaacat aagtacagtt gtttttgctg 100980 caatttgttc attgatttgt ccactaagac atgcatgcat gtattcagtg agtatcactg 101040 agtctctact cagg tattggtatg aatgttgtga atatttcttt gctttgatgg 101100 Page 71 715825 ‐ Sequence Listing.txt ataacacaga gctg atacacaaca aaataattat attatttgag tacaattact 101160 atgcctatag ttggaatatt agtccaatat aggc aatcccaggg aatttatcac 101220 ttactgagcg tccatgatgt gcctggccct gtgttaggta ctgagaagag atcaattaga 101280 cagtttctgc aggaagtcac acataggtta acagtgccaa gacaaatcct aaagtaccta 101340 ttatacaagg ggaactataa taaagagcca ggtgagttga aggcaggaga ggtatcattg 101400 taccacaaga taccttgtga tcttgtgtaa atcccctgaa caatcaggaa aagctttatg 101460 gcatagcttt atggtcagag atctcatggg gacaggcagt tagttgcaat gccttttata 101520 gccacatcct tcactcctta accctgcact gtctgccatt cattctctct gtgctttcag 101580 ccttgagaag ctggccaaat ttctcaggac tggaaaataa actggaatga cactcaggca 101640 cttgatatca agattattag ggtcatgatt gtgtttaaga ccctaagacc tcttgatgct 101700 agaa cttt ttttgtccct gttttcttct tttgccccaa gtttcaagag 101760 catgttacag cagcagtata agcatacaca atcaaaggtg attgaagtga ggacaactgg 101820 ctcaatgagc cact tcaactctcc tccc cttg cccggaatgc 101880 ttcaccctca gactttgaca tagcaggctt ctttttgtca ttcagatctc agctcaactg 101940 caaggatttc tctgacctga agttacatat gtgtcacccc ttctggtctc tctc 102000 tatcacatca cctattggac tacctttata gcatttatct ccacctgatt gtgtcctttt 102060 cactgttttt ctttaaactt tttattgtca attttctttc actagatgcc agttccatga 102120 agtaggaaac ctttaccact ggtcttgagt gctcttgaaa gtgtacgtgt ggca 102180 ctcaaaaatg tttatggaat gatcagctgg atgcgtatat ggcaagtggc gagaagccaa 102240 agga caagagtcct ctcc ttgcctgaag aaaacctctt gcaagaatca 102300 taggctgttc ttgagggtgc ctttgccttg gattcgccaa aaattcttct gtttcttttg 102360 tgtgaaaatt ttcccctcat acacagcaat gggcactaag aatgcatata tccagacttt 102420 taca ggatggcatc atag tcttcctttg atctatatac tatgaagcca 102480 taattgctta gccagtatct ttttcaggat ttactccata tttcttattc taggcctttc 102540 aggtggcagc ggct ttcagatata atttagaatt cgga tttgtaaagc 102600 tactcatgct gcagatcttc tctgaaacat ttctgtcaca ttttagaaag ctttacattt 102660 Page 72 715825 ‐ Sequence Listing.txt tcatctgcta acgattttca tctgccaaag agcccatcta cttaaaaagc agatcactga 102720 actt ggcacatatt actttggctt attttctttt gatttttttg ctttgctggg 102780 attacttatt tatgaagaaa gagagaatat tgacttctta ttttagaaga atta 102840 cttgggttga gagttctagt aaat gtatttatct aagttgttaa ctatatcaaa 102900 aatggagcag tcaatctttg gaaatagttc agggtgaaat gtttttagca tgttcacata 102960 ttgc tgtttttaaa taatttggca aagcttattt gcatttccca aattaacaat 103020 tttggccaag aggaaaagct aaagtgttgg tttttctcag ctcaactttt tgggtgtaat 103080 taatttataa gcaagatttt atgaagggag aacagatagg acctttctac aaagtccctg 103140 aata aacaccccat tgttccatcg ttttgtattg cacataggaa aacatccatc 103200 atta ttctgttaaa gggacacaga ttaccagatt tgtaatttta aaaaaggcca 103260 tttgttgatt gagccacttt gcgtataaag ggtggtatat gttgcctgcc gaatttctgt 103320 acaagaaaaa aatcatatat caaaaaaatt tttctcattc atcatataag atgc 103380 attttagtat gtaccagaag aaatggcttt ggcattttct gtttttagca gtctgttgaa 103440 atttcttcat taaagacatt ttctgtttga aggttaaaat gaccatataa atacagatta 103500 attcagtttt aataggtgca tcttcctgtc atttaccact ttctctcctc aatatcagct 103560 acagtgatca attt agcagtgaaa ctgatatatt ctgtttatct tcaaatcata 103620 agctttttgt ttaaatacaa aggaaaatct tatacctctg attttaatat gacaaatcaa 103680 aaagtccaca tccc aactcatccc aaaaaagaga ttgctatcta ctcatcactg 103740 ttctctgctt ctaagatttg tttcccttgg ggttactgtt actt ttcttacttc 103800 caagattgtt tttgtggttt taagaaagaa tctgaattcc aagattattt ttctggtttt 103860 aagaaagagt ctgaaaatct agagattact taccttgtgg tgaggtggtt gtctatgctt 103920 ctgttcaaca aaggcctcat gtactgaatg gaaaaaaagc atcaggacct ataattttct 103980 aggcattatg aata gaggagacaa aaatgatgtc ttgcttcaaa gtcttagatc 104040 tatttccctt ttga ggaatgagaa agagattttt agatgaaaaa caggaagccc 104100 aatgaggacg aata gttcctaaaa tgagcaaaga gataaattta ctcttttata 104160 caac caaatcacac actggtgagt ttcaaaacag tagttttcat ttagaaagca 104220 Page 73 715825 ‐ Sequence Listing.txt aattaagtgg aataattcaa ctgagtttca ctgcaatggg attcattcta gatggttcaa 104280 ctctggaatt aata tctaaggatg ttgctgatag tagtcagcag ataaatacca 104340 gtaagtcgta tacaggtata catcatttta ttgtgatttg ctttattgtg ttttgtagat 104400 aattgtgttt ttacaaattg aaggtttgtt gcaaccctgt caag tcttctggct 104460 ccatttttcc aatgacttgt gctcattttg agtctctgtg ttacatattg gtaatccttg 104520 caatgtttca aactttttta ttat atctgttttg gtgatctgtg atgagtgacg 104580 tttgatgcta ttattatgtt gttttggcac accatgaatt gcacccatat aaggtgggga 104640 acttaatcac taaatgttgt gtgtgttctg actgcttcac gctc ttcccctatc 104700 tctctccctc tcctctggct tccctattcc ctgaaacaca acaatattga aattaggagc 104760 aatg ctacaatgac ctctacgtgt ctgatatggt ttggttgtgt ccccaaccaa 104820 atctcaactt tatt tcccagaatt tccatgtgtt atgggaggca cccagggggt 104880 ggtaattgaa tcatgggagc cagtctttcc catgctattc tcatgattgt gtct 104940 cactagatct gatgggttta gttt ccacttttgc ttcttcctca tttttctctt 105000 gccaccacca tgtaaaaagg gccttttgcc cccagccatg attctgaggc ctcccaaggc 105060 atgtggaact gtaagtccca ttaaagctat ttttgttccc agtttctggt acgtctttat 105120 ctgcagcatg aaaacaaact gtaa attggtacca gtagagtggg gtattgctga 105180 aaagataccc aaaaatgtgg aagtgacttt gggt aactggcaga gtttggaaga 105240 gtttggaggg ctcagaagaa gacaggaaaa tgtgggaaag tttggaactt cctagggact 105300 tattgaataa ctttgaccca tgat aacgatatgg acaataaagt ccaggctgag 105360 gtggtttcag atggagatga ggaacttgtt tgga atga ttat 105420 gttttagcaa aaagactggc agcattttgc cctagagatt catggaactt tgaaagtgag 105480 agatgattta gggtaactgg cagaagaaat ttctaaacaa caaagcattc aagaggtgaa 105540 tgcttgggtg ccattaaaag catttcattg tgaaagggaa acagagcata aaagttcaga 105600 aaatttgcag catgacaatg cagtagaaaa ggaaaaccca ttttttgagg agaaattcaa 105660 gccggctgca gaaatttgca tgagtagcaa ggagcctaat gttaatcccc atgg 105720 ggaaaatgtc tccaggccat gtcggagacc ttcatggcag acctcccatc acagacccag 105780 Page 74 715825 ‐ Sequence g.txt agga ggaaaaattg tttttctggg ccaggcccag ggtccctgtg ctgtatgcag 105840 cctaaggact tggtgctcta tgtcccacct gctccagctg tggctgaaaa gggccaacac 105900 agagctcagg ctgtggcttc agagggtgga agccccaagc cttggcagct tccatatggt 105960 attgagcctg tgggtgcaca aaga actgaggttt gggaacctcc gcctagattt 106020 atgt acggaaatgc ctggatgccc aggcaaaagt ttgctgcaga gttggggccc 106080 tcatggagaa cctgtgctag ggcagtgcag aaaggaaatg tggggtcaga gcccccacac 106140 agagtccctg cact gcctagtgaa gctgtgagaa gagggccact gtcctccaga 106200 ccccagaatg gtagatccac caacagcttg cactgtgctg ctggaaaagc cgcagtcact 106260 caatgccagc ccatgaaagc gagg gagactgtac tctgcaaagc gtag 106320 agccgcccaa gaccatggga acccacctct tccatcagcg tgacctggat gtgagacatg 106380 gagtcaaagg agatcatttt tgagctttaa agtttgactg ccctgcggca tttcagactt 106440 gcatggaccc tgtaatccta atcctattgt tttgtccaat ttcttccatt tggaacagct 106500 gtatttaccc aatacctgtt gtatctagga agtaactagc ttgcttctga ttttacaggc 106560 ttataggcag aaaagatttg ccttgtctaa ggtaagactt tggactgtgg acttttgggt 106620 taatgctgaa atgaattaag gggg actgctgaga aggcattatt ggttttaaaa 106680 tgtgaagaca tgagatttgg aggggccagg gccagaatga tatggtttgg ctgtgtcccc 106740 acccaaatct caccttgaat tgtatctccc agaattccca caggttgtgg gagggaccca 106800 gggggaggta attgaatcat gggggccagt ctttcctgtg ctgttctcat gatagtgcat 106860 aagtctcctg agatctgagg tcag aggtttctgc tttcgcttct tcctcatttt 106920 tctcttgccg ccaccatgta agaagagtct tttgcctcct gccatgattt ggagggctcc 106980 catacatgtg taag tccaattaaa cctctttttg tttccagttt cagatatgtc 107040 tttatcagca gcatgaaaac aaactaatac agtgtccaag ggaaaggaaa atgt 107100 ctctcacttt atta agcttagtga ggaaggcatg ttgaaagcca atataggcta 107160 aaagctaggc ctcttgcacc aaagagttat ccaagttgtg aatgcaaagg aaaagttatt 107220 gaaggaaatt aaaagtctac gaat acataagtta ttaaaaaaaa aaaagtgaca 107280 tagt gctgatatgg agaaagtttg agtggtctgg atagaaaatc aaaccagcca 107340 Page 75 715825 ‐ Sequence g.txt caacattttc ttaagccaaa gcctaatcca ggcc ctgactctct tcagttttat 107400 gtaagctgag agagaaagct acagaagaaa tgttggaagc aggt tggaaattta 107460 agaagccatc tgtgtaataa cataaaagta caagatgaac cagcaggtgc agaa 107520 ggtgcagaaa gttatccaga agatatagct aagatcagtg atgaagatta ctaaacaaca 107580 gattttcagt atagataaaa tagccttcta ttggaagaat acgtcaatag aagatctaag 107640 atag ttagaaagaa aaagtcaatg ctgggcttta caaa aagg 107700 gaaggctgat ccttttttta tgagttgatg aagttggtga ctttaagttg aagccattct 107760 ccccagcctt gctagagaaa ccaaaagtca aattcaggaa agaa cccctgcaag 107820 attctacaca agaagatcat accccagaca cataatcatc agattttcca aggtcaaaat 107880 aaaagaaaga atgttaaaat cagctagaga gcaagggcag gtcacctaca aaaggaaccc 107940 catcgggcca acaacagacc tctcagctaa aaccctataa gccagaagag ggcc 108000 tatattcaac attcttaaag aaacaaatct tcaaccaaga atttcatatc cagctgaact 108060 aagtttccta tgtgaaggag aaagaagatt cagagaagca aatgttgtgg gagtttgtta 108120 gtaccagacc tcccttataa gagatcttga aaggagcact aaatatagaa aggaaagaca 108180 gctaccatct aatactaaaa cacacttaaa tacacagacc agtgacacta taaagcaacc 108240 acaaaagcaa gccagcataa ccagctaaca acacaatgac actatcaagt tcacacatat 108300 caatactaac cctgaatgta aatgggctaa atgcctcact taaaaggcac agagtggcaa 108360 gctggataaa aaagaaagac ccaatggtat cctgtcttca ccat ctcacatagc 108420 ctcaaaataa aggggtggag gaaaatctac caggcaaatg gaaaacagga aaaagcaggg 108480 gttgcaatcc taatttcaga gact ttaaaccaac aaagatcaaa aaagacaaag 108540 aagggcatta cataatggta aacggttcaa ttcaacaaga aact accctaaatg 108600 tatatgtacc caacacaaga gcactgtatt cataaggcaa ggtcttagat acctacaaag 108660 agacatagac acaa tattagtggg agacttcaac actccactga cagtattaga 108720 tcatcaaggc ttaa caaagacatt taggacctga actcaacatt ggactaaatg 108780 gatctgatag acctttacag aactctccac ctaaaaataa caaaatatac attcttctca 108840 tcaccacgtg gcacatactc taagattgat cacataattg gaaacaaaac aatcctcagc 108900 Page 76 715825 ‐ Sequence Listing.txt aaatgcaaaa gagctgaaat catacaattt caaaaatcag agggccctta agaattatgc 108960 taaatctact ctgtctatac tctataaatg gaacacaata taat agtacacctg 109020 tttacagtat ggcttgctga atattttaag gccacagttg agacctcctg cacagaaaaa 109080 aaagattttt ttctaaatat tagtcctcat tgagaaagca cccagtgacc aaagggctct 109140 gatggagatg tacaaggagg ttaatgtagt tttcgtgcct gttaacacaa tgtccattct 109200 gcagcctatg tatcaaggag taattttggc ctttaagtct tattatttaa gaaatacatc 109260 ttgtaaggct atagttgcca tagatagtca ttcttctgat ggatctaaga aaaatacatt 109320 aaaaacctta tggaaaggat ttaccatcct agataccatt aaaaacattt atgattcata 109380 ggaggaggtc aaaatatcaa cagc agtttagaag aagttgattc caattctcat 109440 agattacttt gaattgattc aagacttcag tggagaaagc cgctgcaagt gtagtggaaa 109500 tagcaagaaa acttgaatta gaagtggagc ctgaagatgt gactgaattg ctacagtctc 109560 atgataaaac ttgaacagat gaggaatcac tgga tgaacaaaaa aatagtttct 109620 tgagatggaa cctg gtgaagatgc catgaacact gttgaaatgg caaaagattt 109680 agaatatgac ataaacttag ttgataaagc agcagccaga tttgagaaga ttgactccaa 109740 ttttaaaaga agttctgtgg gtaaaatgct gtcaaggagt atcacatgct acacagaaat 109800 cttttatgaa aggaagaatc aatcagtgtg tcaaacttta ctgttgcctt attttaagaa 109860 attatcacag caga cttcagcaac catg atcactcaga aggtgtcaac 109920 attgagacaa gactctccac cggcaaaaag attatgactc ggct cagatgatga 109980 ttagcatttt tagcaataaa gtatttttaa attaaagtat atacattgtg ctctttttag 110040 acataatgct cttgcacact tactagacta atta tacacgtaac tttt 110100 ttttttgaga cagagtcttg agcc ggtg tgcagtggtg caatcttggc 110160 tcactgcaag ctctgcctcc cgggttcacg ccattctcct gcctcagcct cccgagtagc 110220 tggaactaca cacc acaatgccca tttt tgtattttca gtagaaacgg 110280 ggtttcacca tattagccag gatggtcttc atctcctgac atcc accctcctca 110340 gcatcccaaa gtgctggtat tacaggtgtg agccaccgcg cctggccaga cataactttt 110400 atatacagta ggaaaccaaa aaattgtgtg gcttgcttta ttgagatatt tgcttcattg 110460 Page 77 715825 ‐ Sequence g.txt cagtggtccg gaactgaact gcagtatctt atgt ctgtattcaa gtttatattt 110520 tgacatacat tcttctttac ttgttaaaat catggtcacc tcattattat atgactgatc 110580 agaatttgca gggttgcttt gaccatatac cattgttcta caactacgca gatgtctgag 110640 tcctaaaggt gaatctgtct ggccagttct gggtttaacg gcctatataa aaagtagatg 110700 ttacacacct tgtataactg aagcgcccta tcacggacac agcttaactc ttgggtgggt 110760 cacttagtct gcttggttga ggtttcagtg cttttcacat ctacagaaat gtcctatttg 110820 tctaaggcaa ttttatgaag taaatttact cttgtcatcc tttccaacct gaaaatagag 110880 taat ttttagcatt ccattattac gatg gtcttcagtc ccct 110940 gaatttatta cactggccct atcttcttca cctgaaataa gttaaatgta gaattagcac 111000 gaaa tagaatgaac ttcttccgga atgggaatag gaaatgaaag agagtaaatc 111060 agaagtgaat cacttctttt tttt tttttttttt gctttgcaaa tttt 111120 tttccagctt tatttaggta tgatcagcaa ataaaagttg tatatattca aggtgtatga 111180 catgatgatt tgatatatgt gtacatttta taatgatcac catgatcaaa ttaattaaca 111240 catccttcac cacacagtta ccatttgtgt gtgc aagaggaggt aagggagttt 111300 aatcattttt gaacactagc tacaacataa ttcaattaaa attctgagaa agaagaaaaa 111360 ttgtcatgca gctgtttaat agca ttaactgaca aaatccaagt cttatgatga 111420 atactcagtc aaattttcat gaatgaatgg gagcctttac aatt gttgtcatgg 111480 aagaaaacac taacactgtc ttacacagta attcaagtta ccaattgagt taaagtagca 111540 agatgagcca tggttgtaat tggc ggtg ttcttatcta atctgctacc 111600 tagtttgcct ttttgctcta aaatggtgac tatgttagaa ttcaaagaat aaaaggcctt 111660 tatcctttca ggggaaatac aagtaacaag cttaattttt tttttcttaa cactgatgaa 111720 actcatttgg ggctgtggaa attgctgcta gcattgaacc tcttattaac attcaaggtg 111780 tgccagtttt gcacaagctg tgtcatattc agagatagat tgttggcaca aactaaggca 111840 cttattctct tgttttttca cttctttcaa taagaacaga taaatatact atttctagat 111900 aagcagttga aactgttctg ctcatctctt tggaataggt ttgtgggggt atcactgtat 111960 gacatgccga agaaatatac aagggaaatg ctcccgcata cattgagata taaatgaatg 112020 Page 78 715825 ‐ Sequence Listing.txt cctattttag aatacgtcat ttcttaaaag taaaataagt tttggctggg cgcagtggct 112080 cacgcctgta atcccagcac tttggaggcc aaggtgggtg ctga ggtcaagagt 112140 tcaagactag cctcgccaaa acagtgaaac cccatctcta ctaaaaatac aaaaattagc 112200 cagacatggt ggtgtgcgcc tgtaatccca caga ggatgaggca ggagaattgc 112260 ttgaacccag gtgatggagg ttgcagtgag ctgagatagc accattgcac tccagcctgg 112320 gcaacagagt gagagtccat ctccaaaaaa aaaaccaaaa agtaaaataa gtttttaaag 112380 tcactgattc tgtttctaag gaattctcag ctggggcttc tgagtcaatt ctcgatggtt 112440 agaacttatg agtagcagaa aaagaaaact actatggatt ttctctacaa tgatttgaga 112500 cagtgaatgg ggctttctgg caggttagca gttaggaact cagatgacca tagacttttt 112560 tttttttaga gtgggtctcg gtctcactct atcacccaag ctggagtgcc gtggtgtaat 112620 catagctccc tgaagcctcg acctgggctc aagcaatcca cagatttttg aagttcaccc 112680 gttg tgttctacac agaggttcca ccttttgctg ccttttatgg ttactatatt 112740 attattttga tgtttcttaa ccagctgaat cacattgtag tatatgaaat atgttttggc 112800 tcttgtttta atggttattt agat ttcacaatgg cccaatgaaa attc 112860 attgctattt attc acta aacatgactc acgg aaag 112920 tcttggttta tgtgtgactt ccaggggaga gagattgaga accatctgtt aatcattttg 112980 tccctaaact agagtttttc aatggagtac ttgggcagtt gaattagtat gtttctcgta 113040 ggctagtgag aaaaatagct tttttttttt ttggcattaa tcagactgct gacccacatc 113100 tctgggaata cttgtgacaa gatccagcct gacaatatca catatgattt gcttttcttc 113160 ggga cacattgtgg cttttctctg gaatctgtga tgct cctgagccta 113220 gaaactggaa ctgagaaagc tcttcctgat catataacaa taagtcttgt gagggtcaac 113280 ccttgagcca tgagggcagc ttgaaggaac atggggttga gagtcaagtc atcagaactt 113340 ctgtttattt ttctgtgtaa tatttaggga atgt ttaactctag gcaaaggtat 113400 agatttggag gtctttgata tagatgatag agat atag atgaaatata 113460 ttttagcata caaaggaggc tacaatacac actcatgtac ctgtcactcc aatgaattca 113520 tcaaatgtaa acattttccc caaatctgct tcttagctgt tattcgtaaa gaaacaaatt 113580 Page 79 715825 ‐ Sequence Listing.txt gtacagaaaa atttgaaggc ccccgtttta ccttccccag tctcattatt ttctctgcca 113640 ccccagagaa aacaactgtc ttgcataggt atttatataa ttctgtttta tactttgcca 113700 cttttactac atatatgaag catgcttgtt atga acataaaata tacatgtttt 113760 actgtaagtg tggaatgtat tctagaattt gctactttta ctacaaatat tttattttca 113820 gaatttaccc ttgttattat ctag ttcatttttt aattgccata tattactcca 113880 tcttatgaaa ataccacaat attc ccatactaat cagaatttga attgatacaa 113940 atta aaattaataa tgctgaaaga aatgttcttt ttatacattt ccctcagggt 114000 gcatgtgata gagttcttct cacatatata tcagtgtact tgctgtgtct taggatatgt 114060 acaattgcat gtctattaga aaat tgctctgcaa agtactcata ccagtttcca 114120 ctcctaccag caatgaatga gaactttgtt tcgcaggtca ttgccaacac ttgattatta 114180 tcagatttaa ttatttgcca gttgatggat gtgaattgct ctatcactgt attc 114240 attactttga ttatttataa cattaggtat acttttcata gggccattta aatttcctct 114300 catctgaatt ttct cctcttcgtt gattcttcta ttatcttttc ttctctttat 114360 taatttatag aaatgtatgt gtgatcctaa tatgtgtcat aatatctatg ttcatatttc 114420 atatataaat ataatgaaat acttgtctct gttatatata ggttgaaaag tttgctccct 114480 atctgctgat tgcattttaa ttttgttcat ggcatctttt aacacacgtg atttttaatt 114540 tagt taatattttt tattactcta gattttgaga attgctcaag aaatgacttt 114600 attttgcata gtcatatgct tttt taatctactt acaatagttt tatgttaaat 114660 atgtcaacct ttgtttcacc cggaattttt tatatgtatg gtataaagca taaatcaatt 114720 acta ttgagaatgc ttttattata ttatatctta ttctattcta tttttatttt 114780 tccataagtt attggggtac aggtggtatt tggttacttt agtggtgatt tgtgagattc 114840 accc atcacccaag cagtatacac tgcaccatat ttgttttctt ctca 114900 tccccctccc acccttcccc caaagtcccc aaattccatt gtatcattct tatgcctttg 114960 catcctcata gcttagcccc cacatatcag tgagaacata tcatgtttgg ttttccattc 115020 ctgagttact tcacttagaa taatagtctc catc caagtcactg ccattaattc 115080 attcctttct atggttgagt agtattccat catatatata atgt atgtatatat 115140 Page 80 715825 ‐ Sequence Listing.txt atgtacgtat gtatatatgt atatatgtaa gtatatatgt acgtatgtat atatgtatgt 115200 atatatatgt acatatgtat atatgtatgt atatatatgt acatatgtat atatgtatgt 115260 gtac atgtgtatat atgtatatat atgt acatgtgtat atgtgtatat 115320 atgtatatat gtacatgtgt atatgtgtat atatgtatat atgtacatgt gtatatgtgt 115380 atatatgtat gtatatatgt acatgtgtat atgtgtatat atgtatgtat atatgtacat 115440 atgt gtatatatgt atgtatatat gtgt atatgtgtat atatgtatgt 115500 atatatgtac atgtgtatat gtgtatatat gtatgtatat atgtacatat gtatatgtgt 115560 atatatgtat gtatatatgt gtat atgtgtatat atgtatgtat atatactata 115620 gtttctttat ccactcgttg attgatgagc gttg gttccatgat ttttcaattg 115680 caaattgtgc tgctataaat gtgtgcaagt atctttttct tataatgact tctttcctct 115740 gggtagatac gtga gattgctgaa tcaaatcgta gttctacttt tagttcttta 115800 ctcc acgctctttt ccatagtggc tgtactagtt tacattccca ccagcagtgt 115860 agaagtgttc cctgatcacc gcattcatgc caacatctac tgttttatta ttattttttt 115920 tattatggcc atccttgcag gagcaacatg gtatcacatt gtggttttga ttgcatttcc 115980 cttatcatta gtgatattga tttc acatatttct tggccatttg tatatcttct 116040 tttgagaatt gccttagccc actttttgat gagattgctt gtttttttat tttcttattg 116100 atttgtttga gtttgttata gattccagat attagtcctt tttcagacgt atagattgtg 116160 tttc tcctactctg tgggttgccc atttactctg ctgactgttc cttttgctgt 116220 gctc tttagtttaa acta tttatctttt gtttttattt catttgcttt 116280 tgcgttcttg gtcatgaaat ccttgcctaa gccaatgtct agaagagttt ttccaatgtt 116340 atcttctagt atag tttcacgttt tagatttaag atcc atcctgagta 116400 gattttttgt atgaggtaag ggat ccagttttat tctcgtatat gtgactagcc 116460 aattatccaa gcaccatttg ttgaaaaggt gtcctttccc cactttatgt ttttgtttgc 116520 tttgtctaaa atcagttagc tgtaatattt ggatttattt ctgggttcaa tattctgttc 116580 cattggtcta tgtgcctatt ttcataccaa taccatgctg ttttggtgac tatggcctta 116640 gagtatagtt tgaaatcagg cagtgtgatt cctccagatt tgttcttttt ccttatttct 116700 Page 81 715825 ‐ Sequence Listing.txt tgctttggat atgcaggctc ttttttggtt ccataagaat tttagaattg ttttttctaa 116760 ttctgtgaag aatgatggtg gtattttgaa ggagaaggtt ttgaatttgt aggttgcttt 116820 tggcagtgtg atcgttttca caatattgat tctacctatc catgagcatg ggatgtgttt 116880 ccatttgttt ggtcatctac gatttctttc agcagtgttt tgtagttttc cttgtcaagg 116940 aact cttttgttaa gtatattcct aagtatttta ttttttattt ttttggcagc 117000 aattgtaaaa ggggttgagt tttg attctctgct tggtcgctgc tggtgtatag 117060 aagagctact gatttgtgta cattaatctt gtatctggac atgttgctga attcttttat 117120 cagttctggg aactttctgg aggattcttc agggttttca agttaaatga tcatatcatc 117180 agcagacagt gacagtttga cttccttttt accaatttgg atgctcttta tttctttctc 117240 tcatctgatt gctctggcta ggactcccag tactatgttg aagaggagtg gcgagagtgg 117300 gcatccttgt ccag tttccagagg gaatgctttc aacttttccc gtat 117360 tatgttggtt gtgggtttgt cataaatggc ttttattaca ttgaggtatg ccccttgtat 117420 gccaattttg ctgagagttt taatctgaaa gggatgctgg attttgtcaa atgctttttc 117480 tgcatctttt gagatgatca tgtgattttt gtttttaatt ctgtttatgt ggtgtatcac 117540 atttattgac ttgcatatgt taaaccatct ctgtgcccct ggtatgaaac ccacttggtc 117600 gatt atctttttga tatgttgtca gattcagtta gctagtattt tgttaaagag 117660 tttagcatct atgtttatca aggatatcgg tctgtagttt tcttttttgg ttatgtcctt 117720 tcctggtttt ggtattaggg tgatgctggc ttcatagaat ggattaggga cctc 117780 tatc ttgtggaata gcatcaaaag tatc aattcttctt tgaatgtctg 117840 gtcaaattct gctgtgaatc catctggtcc tgggcttttt gtcggtaagc ctttaattac 117900 catc tcactgcttg ctattggtct gttcaggtta tctaattttt cctgatttaa 117960 agag ttgtattttt ctaggaattt atccatctct tctaggtttt tacg 118020 tgcacaaagg tgttcatagt actcttgaat gatcttttat atttcagtgg tgtcagttgt 118080 agtatccccc attttgtttc aggt tatttggatt ttctctcttc tggt 118140 taatcttact aatggtctat tgattttatt tatcttttaa aataaccagc tttttgtttt 118200 catt tgtatttttt cttttaattt tatttagttc ttctctgttc ttggttatgt 118260 Page 82 715825 ‐ Sequence g.txt cctctcttct cctcggtttg ggtttggttt gtccttgttt ctctagttcc ttgaggtttg 118320 accttagaaa gtcactttgt gttctttcag tctttttgac ataggtgtta gggctatgaa 118380 ctttcctctt agcactgcct ttgctgtatc ccaaaggttt tgataggttg tgtctttact 118440 gttgttcagt tcaaagaatt ttttaacttc catcttgact tcatttttga cccaatactc 118500 attcaggagt aacttattta atgt atttgcatgg ttttgacggt tccttctgga 118560 gttgatttcc aggtttattc aatgtggtct gagagagtac ttgatataat ttcaattttc 118620 ttaaatttat tgaggcttat tttatggcct tggt ctattcttgg agaaagttcc 118680 atgcactgtt gaatagaatg tgtattctgc tgga tgaaatgttc tgtatatatt 118740 tgttaagtcc atttgctcca gttt aaatccattg tttctttgtt gtctttttgt 118800 gacc tgtctagtgc tgtcagtgga atattgaagt ccccactatt attgtgttgc 118860 tgtttctctc atttcttagg tctattagta attgttttat aaatttggaa cctccagtgt 118920 taggcgcata tatgtttagg attgtgatat tttcctgttg gctt tttaccatta 118980 tatagtgtcc ctgtttgtct cttttaactg ctgttgcttc tgtt ttgtctgata 119040 caagaattgc tacccctgct ggcttttggt gtccatttgc atgaaatgcc cacc 119100 cctttacttt aagtttatgt gagttcttat gtgttaggtg agtctcctga aggcagcaga 119160 tacttggttg gtgagttctt atctattctg ctgttctgta tcttttaagt ggagcattta 119220 gggcatttac attcaatgtc agtatgagat gtgtggtact gttgcattca tcatgctgtt 119280 tgctgcctgt gtaccttggt tttt tggtgtttgg tttttaactt gtatttttgt 119340 gtcc tatgtgattt aggctttaaa gaggttctgt tttaatgttt ccaggatttg 119400 tttcaagatt tagagctcct tttagcagct cttgtagtgc ggca ggggccaatt 119460 ctctcagcat ttgttcgtct gaaaatgact gtatctttcc ttcatatatg atgcttagct 119520 tgctggatag aaaattttgg actaataatt gttttgtttg aggaggctga agataggggc 119580 ccaatcttat ctagcttgca ctga tgagaaatct aatc tgatagattt 119640 tcctttatag gttacccagt gcttttgcct cacagctctt agaattcttt cttttgtctt 119700 aactttagat aacctggtaa caatgtgcct aggtgatgat ttctttgcga tgaatttccc 119760 aggtgttctt tgtgcttctt atatttagat gtct ctagcaaggc tggggaagtt 119820 Page 83 715825 ‐ Sequence Listing.txt ttcctcaatt attccctcaa atatgttttc ccaaactttt agatttctct tcttcctcag 119880 caat tattcttagg cgtt taacataatc ccagacttct tggaaccttt 119940 attt tcttattttt ttctttgtct ttgttgaatt gggttaattc aaagaccttg 120000 tcttcaagtt ctgcatttct ttcttctact tgttcaattt tattgctgag actttccaga 120060 gcgttttgca tttctataag cttgtccaat gtttcctgaa gttttgattt tttttcttta 120120 tgctacctat ttccttaaat ttttctcctt cttg tatcatttcg ttgtatcaga 120180 tttccttgcg ttgggcttca cctttctcta gtgcctccct gattagctta ataactaacc 120240 tcctgaattc tttctcaggt aaatcagaga tttttttctt ggtttggatc cattgctagt 120300 ggactagtat tacttttggg gggtgttaaa gagccttgct ttgtcatatt accagagttt 120360 gttttctggt tccttctcat ttggaagctc aggg aaggtccagt gctgaaggct 120420 gttgttcaga ttcttttgtc ccttaatgta gtactctccc tattttccta tggatgtggt 120480 ttcctgtgag ctgagctgaa gtgattgtta tctctcttct gggtctagcc acacaaccag 120540 tctacctggc tctgagctgg tactgagggt tgtctccaca tgtg atgtgaacca 120600 tctatgggtc ccat ggataccagc acagtatttg gggtgtctcc tgcatcctgc 120660 aggagcagtc cttc tgtgggtcct ctcgggattc ctgtttcatt cttgaagtct 120720 agatctattt tttgacagtc taatcctaac accatttact gaggaacact ctttttttca 120780 ttgttctgta cctc tgttgtaaat taagatccca taaatgcctt ggtatttgct 120840 agactttctt tttcttctgt tgttttaaaa ttttctctcc caacaagata aaatattgtg 120900 taaatattat atgtttatac taagcatttt tatcttgtac tgaataatag tgagaatgct 120960 tcaaaatttc tttg ctattaagta taag tacgctatta agtactgtat 121020 ttgg ctgacttatt tttgtcaggt taagaaaact gctctctatt tctagtttat 121080 taagacagtt tatcacaagt ctat aaataatggt ttttctgcac attcgaataa 121140 tcatttgatt cccactttta aattattaat gctgtagatt atattgatag atctgcctga 121200 tattaaacta tccttgcatt cttgatctaa atcttacttg aatgggatgt gttactgtat 121260 tctctctctc tctctctctc tctctctctc tctctctgta tctctcttcc tctcttcatc 121320 tctcttctgc aacatcttaa agcatatttt ggtaaatttg ctttttatag ttattgattt 121380 Page 84 715825 ‐ Sequence Listing.txt tcagaaatat ttctttgaga agctaaaaat gcaaaggttt tatttcacct tgtttcaaat 121440 atagtaatta tctaggaata agaattgtcc attttctacc tattgagaat caaaacattc 121500 acagaacata aacctacttg tttcaaatat ggtagttatc taggaataag gattgtccat 121560 tttctacata aaaa aacattcaaa gaacataagc ctaaaacctc tctttctttt 121620 aacc tacgggaagc ctgtcacttt agtt atgatcaggc tgagcttcac 121680 tcccccttcc tgggctctct ggtagaatat gccctcccaa gtcctcccta gtgtgagtcc 121740 gtcc ccacccatcc cctctatcca ccaccgcccc cgctctcagg ctgccctgca 121800 gttgtttctt aatgcagcag aaggctgcaa caaccacaaa ctacattgcc catgatcaac 121860 ccatgcccat gtccttctgc accccccagt cagactaccc actcccacaa atat 121920 cagtgttccc atatttcatg cattatctat ccttctctca gcag atctagcaca 121980 ttttaattat cctttgtgac agtctctagt cttg tttttttttt tttgtctaga 122040 atttactttc atcttctgat tcacaggaaa tttgttccat attgtttttt tacaagcaat 122100 atctagttga attacccacc tact tttttcctca ccattagttc attcacctaa 122160 taaattctta ttgcatgcct tgtgttttcc tgctattgta catgcctgga aatataggag 122220 tcaaccaaat cgtctctgag ctcatgtagt tgacaatcta gaac agagatgata 122280 aacaagtaaa tatatatcaa aaataattgc catggagaaa gtag tataaggatt 122340 attatttatc taggttgtca ggcaagagct tacagatggg tgacatttga actt 122400 gaaagaagtc tgggagaaaa gtatcccagg gaat agcatatact atttgggatc 122460 ttcaaggaac atcaaagagg ccagtttgtt ggagcaggat gagcaagaag aacgtagtgg 122520 taaatggagg cagagatagt gggtgagagt ggggttggga aaaaatcaga taggactttc 122580 agaccactgt aaatacttgg tcatttactc taagtgagat aggataccat gacagtgtcc 122640 tggaaaaaaa aaagggacat gttcttattt tagtgagacc aatttgggtg ataa 122700 ggagattcaa aagcaaaagc aggtaggcca ttaagaaact ataa tccagataaa 122760 tgttggtgcc ttggttaagg gagataaaga tggagatggt aagaagtgat cgcattctgg 122820 atgtaatttg aaggcatgtc tgagaggatt agttgatgga gtgttactta tggggtatca 122880 gtgaaagaat agaggaaagg cctgagaatc tggaaagatg aaggtgatat ttactgaaat 122940 Page 85 715825 ‐ Sequence Listing.txt ggcctacact tgaa tagattagga agtaaaattg aaagtctggt tttt 123000 ataagtttga gacgcctata tcaa tatt aaatagtgaa ctggatatat 123060 gagcctgtag ttcaagaaag aggtctggat taaagttatg atttggacaa catcatcata 123120 tatgtggcat catg attccaaatg agataatcca gggaataact atagagaaaa 123180 gaggagagga ggataatttc tggtgatatt tcaatgctaa gtggttggga aaatgaagag 123240 aacacagtga agttgaccag gatgaagtac ttactgaggt ggaagaatca atggagaagg 123300 gtgttcaaga tacaaaatta agacagtgtg tcagagaagt ggggagtgat ccattgtggc 123360 aagtgttatt cattggttaa ataagatgat taagaatttg ccacaatgtg gaagtcattg 123420 gtgactagag caaaagctat tccattgatg agat taaagcctga taag 123480 tttaagaaat tgggcaagga ggaattaaag aaaggagaat attt cttcaagaag 123540 ttttgattta gaggggagca gagaaatggg tcagtaactt catgagcagt aactgaaata 123600 ggagaaatta tcctttttct aaaaggagat aattttagtg cacacttaag gtgattctta 123660 tcttcctgca aaaatagctc ctttaggtat ttttcaaaat tttatacatg tatatttcta 123720 ttccaatcat ggta caagtgattt ttggttacaa attg tatggtggta 123780 gtgaagtctg agattttagt tcatccatca cccaagtaat gtacattgca atac 123840 accttttttt atccctcagc cacccctacc ccctcctcag tctccagtgt ccattatatc 123900 actctgtatg cctttgcata cccatagctt acctcccact tacaagcaag aacttcatgg 123960 tatttggttt tccattcctg agttacttct tttagaatag ccag ctccatccaa 124020 gttgctgcaa aagacattat ttccttcttt tttatggctg agtagtattc catggtgtgt 124080 atatatcaca ttttatttat attg tttgatgggc atttaagttg tttctacatc 124140 tttgcaattg tgagctgtgc tgtgataaac atacatgagc aggtatcttt ttgatataat 124200 gacttatttt cctttaggtc gattcccagt agtgagattg ctggattgaa tggtagatct 124260 acttttagtt ctttgaggaa tatt gttttccatg gaggttgtac taattgacat 124320 cactaccagc agtgtataag taatcctttt tcactacctc tacaccagca tttattgttt 124380 gtttttggga tgtt tttgtctttt tataatggcc attctggcta ggaaaaggtg 124440 gcatatcatt atggttttaa tttgcatttc cctcctttag gtattattta atgagagtct 124500 Page 86 715825 ‐ Sequence Listing.txt tttggtggta aagtatctta gttttcatgt gtgctcacac acacatacac agagtcttta 124560 gtgacaggct agttgggtat caaattctga attgatgttt ttttctctaa tacttttaaa 124620 gtttatttgt gcat ctgttgttac taaataaaaa tcttccacca gtccatttga 124680 gttcattagc aggtaatctg cctcttattt taagcacttt taaagatttt tctgtatctt 124740 gatgccatat gatagatcta ccttttatta actc agtaattact gtgggctttt 124800 aatctgcaaa ctcaatcaat tattcgattt tataaaatta tcagtaataa ccttttctat 124860 aactgattat ttgcagttga attaaatcct ctctttctgg aattccaatc atatgtgtgt 124920 tggagcttct caatctgccc tccaaggctc gtaactgctc ttttaaattt ttcagtacta 124980 ctctcaattt tttttttaaa aaaacaacct aatattgcag tgtttggcac agaagaagtt 125040 caaagtacaa ctttgcactg ccacgttgac cagctattct ggcactggtt attctttaaa 125100 gttattttta acgt accttatcag gcagcaggtc tcaaaaccta gggaagctta 125160 aaagcctaaa ggcagcctgg caaaaatcaa gctgattaaa atgctctttc ccattttctt 125220 gtcctcctat gccctcatcc ctaaagaata gtgagagggc cttccttaaa tgta 125280 taaaatagca gaaagaaaaa ggggatccag tgag aagacatact tagataattc 125340 acagtaaatg ttccaaataa tattcagcct cactaattct caaataaatg taaaacaatg 125400 gcagatcatt tttatccatt gtga aaataggagg aaaagaacat tttgctgaca 125460 attgttaaca ctga aattctcttc ttgtctagtt tgaatctaaa ttaggacagt 125520 ttgaaagcaa gata aaaa taaa cattctaccc ttccatgtag 125580 caacattgct tctgtgaatc aaccattagg caaataaatg gaaataacaa accaaatttc 125640 cctc ccaagagatg tttattgtaa cattactgat aatattgaaa aactagaagc 125700 gatctatatc agtgatccac tttg actgtcactc accgtaagaa aatattaggt 125760 atacaaagta caga cacacccatg catcaaaaag ttccatataa ggaaaccgtt 125820 caatccattc catttattta aacaagccaa tgaacaaagc tggctttgat ccactaaatt 125880 gatcctacaa cctaagagta ggttatgact cagtttgaaa agcaccaatc tgaatgtcct 125940 ataaaagata ggaa tatgaattaa atttgatatt tttt tacttttttt 126000 tgtttgaggg tagttggagg ggtactatgt ttcttcagcc agcaaggaag ataatgtttc 126060 Page 87 715825 ‐ Sequence Listing.txt tagataactc catataatgg agatttactg taatgatacc gttc tactatgccc 126120 agccattctt atgtatctgt ctctcaatgc atcatgggtc ctttatggat tcttttgtga 126180 tgtcctcaag cttcctgtcc actccctagc aacttgccca aactgataga ctga 126240 atcagtcaac atctgatttc aagcattttc tcag cctttggtat taggacttta 126300 ttctcaatct aatcaattaa tattagctga gctaggttga tttcatttga atcaacaaag 126360 aattgctaaa agctgcattt cctagaaaat gtggcaatat aattggcagg tacttgagag 126420 tctttaatgt taaatggaaa aaaaataaaa aataataaga gacaactttt gagc 126480 tcgg ttttctttag atattttgtt agagacaaaa aaggaatcca gaatttattt 126540 tatactacat tagtacttaa cagatttcta cataagcaag tattatgcat ttgtaatcag 126600 atat caaaattagc tctgtggaaa atgatcatct tgcaagcaag catcatgtac 126660 ccctactttt gctc atcttcttga tgtaaatatg ctgc gcttgaaatt 126720 ctgtttgaag tggaaatctt catgtttgtc ttacaaatac catctcagag tacattgctc 126780 agtataaaac ttgttttggg ggta caaaaacctg caaagatata gtccaggctc 126840 cttttcccaa agtccttcac tttcctactc ttagtataac cattattttg taaaatttaa 126900 ccct aataacttgg ggtttgggaa tttgatttga ggtaacatgc ctcagagtat 126960 cacctatttt ttattaaacc tttc tatctgacaa agatgtgcat gggc 127020 cttaataatt cccccaaata aaactattcg taagttctaa cagttccaaa tacttttggt 127080 ttcagcacac taataggatt tatagctgtc ttagataagg agcagtatct tctaaagctc 127140 atgaaaaagc catatcagaa tgccatgtgt tcaggtatat ttct ttatggtatc 127200 aagaataaaa tctcagctta tgttttcact caagtgttgt gtgattactt tttcccatta 127260 ctctttcgat tgagcctgaa aaatgaggtg aaaaaatctt tctctttcaa ggatgaacta 127320 gaaggatcta ggctggctgg tcaccaaacc actgactagt tggccctttg tctttttata 127380 acccctcatt gtctgggatc caacatcata gtgagtctca gacatgttcc acaagtctag 127440 atagccctca tccatgtgtt cagtggtcca gcccatcagc atccaagcca gcagggtgag 127500 gaggggaagt gtaggggatg gccc tgaaggatgc atatgccact tccattcagg 127560 ttgc cagaacatag tcatgtgacc acagttagct gcaaggttgg ctgagaaatg 127620 Page 88 715825 ‐ Sequence Listing.txt cctttcactg ggttctatta ctaactgaaa atgggaagag tgaaagttgg ggataactag 127680 taaatattag caag tcatggattg tggtattaat tccatgtgct aggaaggtca 127740 tttaaatgtt ttatgcagaa ggatgccatg atgataatta tgtttcaaag catatttgtg 127800 tgtgagagag agagactgaa agagaaagtg agataaatgg attggagaga atttgtctga 127860 gtgttaagag gccattctca aacccaagtg ggaaatggtg gctagtaaca gtagtgagga 127920 taaaggggga tggaatggac tcaaaagata cagaagagat aaaa gatgaaacag 127980 agga ggaagaaaag acatccagat aactcctagg tttctgattt atactgcaaa 128040 ttctggggat caggtgttta tggaccactg agtttagttt tagaaacgtg atttagaggt 128100 atttgtcaga taggtggttt ctacacattc aaaataagat ttcaaaacat attagccaca 128160 attcacaatc agcaaaattc tcaaatctag tcattgtcaa ctaaactatt aaaatgaatt 128220 ttcccctcta tctc atcttaaagg gtttgtatgt attacatgtc acagtatggt 128280 ttattgcata taaacatggg aaagcaagcc aggcagaagg agtcttgtaa ccagctaaag 128340 gcccagctaa ttcttgaagc agtcataaat catgaacggt cttcttgtgt taatagtgtg 128400 gacaggactg ttggtcacac aaat gagtcacaca gtcttgtgtg tacagcaact 128460 cactccacac tcaatgatgg gaatggtcat gattgttcta actgtgtgag cagctacaag 128520 aattatggca aagctccaga gctagaaagc tggttttttt tttatgtcac ccgagtatgt 128580 aattcactaa atgtttagta ttttatacct tttagttgac gccc tttctaaagg 128640 agatctattt ccctctacta gaaggtaatc agaaaaaccc taaactacgt tttctaaatg 128700 tctt ctgcccaatt gaccaaaata tacttagttg attaggactt tgaagggatg 128760 agatgagggg actaaattaa ggaa tttcagtttt ctaggggttt tctgtaaact 128820 actttatact gctgacaaat ggttaaatgt ttccaatgaa actaagtatg ctaggatttc 128880 taatgagcaa tgaaatttta gaattcattt actcattaat attt acaagatgta 128940 caatgtgcta tcttctgggc atttggggta ctttaatgag gtagcagtga gtaccacaaa 129000 tggtcacttc tgtt cttatactcc ttagagaagg acca gattcagata 129060 cact gctttctacc catccagatc agagcctttg ctgagttcta acgcttagcc 129120 tcag ctgatttggc tgcctccatt gtaataggcc tcatgagact ccagcctagg 129180 Page 89 715825 ‐ Sequence g.txt cctggccttc agttcagcag ccca gagatgtact gggcaaaggt caggggattt 129240 attatatgag gtct gatgtgattt aatttactcc tctggtacca gatatgtgtg 129300 tgtgtgcatg agagagagag attgagaatg actgatttgg tttt gtgaaggttt 129360 atatatcaaa gcagaaagac caagaattta gagattaata catgccaagt caag 129420 ctgt gggatcccac cccc tctg tcagatttta accaaatcag 129480 tgtgatgtga tctgcttgca tatatgagtg aaagaaaaag gaaatttaaa aagttcttga 129540 tataaagcct ggaggaaaca aaat ccagcctcta tttcagcaat atctgccgga 129600 ctattggtta gtattccctt actgttactt attgtttgat taaaaggctg atagtcaggg 129660 tttttttttt cttacttttg cattttttag atataaatct ttaatatatg gcca 129720 gatgttttcc tttctcctcc cacttcgttc ttccctcttc tgggttaatt tctcattgtt 129780 ctctcttccc cttacttctc tgcccttttc ctttctactc taagcgaaac ttcttttttt 129840 ctgtgctgga gtttataaag tattctttta ggcaaagaaa gcctttggct gccttcctcc 129900 ttgtctggtc accatcaaga tataattttg gttttcaaag ctct gaaggaagga 129960 ctagttttct gagcatttag agagcagata cattttgaga aagtcaacag agatagtaat 130020 ttgcactcag gaaatactta agggttttaa ttctgttcca tgtgttacat ttcaacagtt 130080 tacattaaga aaagtattgt aaagagaagt gataccacaa ttgcatgttt attttgcatc 130140 tttagtctga gagatggtca gtactttgaa ggaaagagaa atagggcttt gtctccttct 130200 gcttcttgct atacctcttt tcagattaac tctgatgctt tgggtttctt actgcatgcc 130260 tgattaaaac ccatcccata atgcctgatg tgatgggaac caccacttat tctatctcaa 130320 tggaaagtat tcacatgagc tttcaacaga aggacattct cccacctctt ccaaacacct 130380 ctttgaaaac cgtgtccatg ggcctttatt catgtcttca tgtt taaaactggt 130440 tgtgctaggt agtgggcaat ataaagatga gccacaggag agagatgaca atatcactga 130500 ttccttatag tgctgtaata agggtttatt aaggctgtga tagaagtaga gaggagaggc 130560 acctgacttc acttgggagt gttg ctaaggtgtt tctaagttga aatgtccttg 130620 agctgaggtt aatg aaag atggattaag tgagaagagt ataggaggca 130680 gcagggccag aggtgtgaat agcccagaac cttctgagaa gattcctttg tggacggaag 130740 Page 90 715825 ‐ Sequence Listing.txt aaaggggagg tttgtggaaa tggtggaaga taaggtagga caca tcagatcaca 130800 catggctgga tgtacctctc taaaagtact ggggggtttg aaacagaggc tataaattgg 130860 cagtttaaga aaatcactgt ggtgtcagtg tgaagaatac gcaa aacg 130920 aggattattt tcagaaattt aggcccaatt tagtccagat gtcagggcta gtttggagta 130980 aatttctttc tttaattact ccagggctct tgtattgctt caaagaaagt agaaagtgga 131040 actcaccctc attcagggag ggtgggcaag cgaccagcca gaag gccaaagagc 131100 caggtcacct tgtgcccgca cttgttatga tttgtttgta ttgtctgcct gatgatcaat 131160 gatattagct atgacagcac gtatgagcct ggggtaagtg tgtcttcttg ctacttgaag 131220 tgcttcttga aaatagtggc aggctgaaga caacaaggaa aaaa tgga 131280 ctggggacag tggt gctgctccca gcttggccgg ctcc gggggcttag 131340 acacattact tcacctctct gggcttaact taccccattt gtaaaatgca acctttagac 131400 taacactgtt ctcggggcca tgttcagcct ctggcttctg tcattgtgat cctgcctccc 131460 caaggttccc ctgggcccca tcactactaa ccctaggctt ctagacattc tgattcatag 131520 agaaatagga aagcccattt atcttaagtt aatgtcagcc acag ttgtgtctta 131580 aggaatctaa tctagtgaac atggaaaata attttctaag gaaaaaaatt gtgattggtg 131640 ttctgtcctg aactgatggc aaaagggaag cagaaccact tcacacatct caatctctct 131700 gttttttcct ttttatcctc ttgaattttt ctgcctgttt gtctttcaaa agtagagagg 131760 agtttgaatg ctga tgag ggtagccacc gatgggggaa gctggactgt 131820 gggaagccga gttctgccac ctgacaaagg ggcacgtgtt tagtgtttat ttggcatagc 131880 agctgttcag gtggagccca ggcagaattt cgtt gggaccttcc atacctttct 131940 gaaattctct tgcaccaaca cccggcaccc tcaggttatg ttctgctgcc caaagcctga 132000 ggctcaactt ctagccctct cttttctctt ttaccggaac taacttctaa aaatccagaa 132060 agta gatggtggtc ttcc tgaggtggaa agagaacctc tagtgcctct 132120 ggctgacatt atatccactg acagatcccc tcccgcacgc atacatgtca catgtttctg 132180 ctcatttatc aaatacagcc catgctttgg tgattgagag cagagtgggg attataagtt 132240 gatgcagtag gcctgtgtct tgcccttaga agtttacaaa cagcaacaca ggcaccaaga 132300 Page 91 715825 ‐ Sequence Listing.txt gctcatctgt tacacccaca gggatttatc atcttgtgac ttggatattg tggaatgttt 132360 aaag gttaaaaaaa aacaatgtag gcacagagga gttaacagct aagttgcggt 132420 ggggagtctg gaaggcttca tggacgtggt gatatttgaa cgtgactttg aagggtaggt 132480 agagtcctga tttgtctaac agtagccttg aaagtaaagg aaacttgacc atgaagaagg 132540 ctgttgaaag tctggagaaa agagaaggta ggagactaag actctaggag aaggtactac 132600 gttccaggga gaatgcagag tcct ccctcatggt gacaagttaa atgtgagaag 132660 ggatggagta accaactggg tgaaccctga tctcattaag caaaataaga agaa 132720 atgaatctgc atgctcataa gatc aggt aggaaatgct gactttattt 132780 tagacagagg ttattttagg tacctgtgga ggtg tattatttcc ctatgtctga 132840 agcacatgtc ctttggttct ttagcatttt gatgatgatg ctccatgtaa actgccccct 132900 aggattttct ataagttttc ttcctcattt gagagtaaag ttttaactgg taacatgatc 132960 acaagtggtt gaaaagttaa aatgttattc atatagcttt ccaatgaggg gagcatgaat 133020 ggtttggtac tgttttacaa gatgtgaaaa ctgatttcac ttaagtagac ataa 133080 agtttatgtg tctgtccctt tggcttcctg gtaggtggac tctg aatcaatagt 133140 ggct tctgatttca aacctctttg gccagccaac tggtttagga gaaacatggc 133200 caggtcattg aattataatt tcctgagtta tgttgtggtg gtcccgtagg acagtaaaca 133260 taagcctcct gggaactgaa cttttaattc aggaggactg aaaacaagct cttctgagcc 133320 aagatttgca aggacatgtt acaaagatag actggccttc ctgcttccac accatttttt 133380 cctccataaa tacatgctcc ttttccgtat ttttcttcta ccctagtctg ttgtagattt 133440 tgaccttggc tgttactttc ctaccaacac attgcctatt tttaagtttc ctggtttgac 133500 ctgatgttaa gatggaaagc agca aactgatgga gatagggcct tccagccttt 133560 ctaactttcc ctgggatcat cttatgttga tttacatgtt caaaaaattt ttaaaaataa 133620 tgta tcagttgatc cagaagtgat tagactctag gggcctgatt agcc 133680 aaacttaaga gatgagccaa tacaccaaaa tgccaatata tttgtttgtt ctctatggca 133740 ctgtcaagca atttcatttc atctgattac tgtgttcatt aaag atagtgaacc 133800 cagaaaacaa gaatcagaag tgac aactgtggag ttggaataga gggaactgaa 133860 Page 92 715825 ‐ Sequence Listing.txt tgaccctcta ttgggtcatg agggagagca tcatcaagct ttgagaaatt attgcacctg 133920 tctctgtgtt gggacatttt tttggtccca ggtagttgga agagacaaag ctgtaaatta 133980 tttactagtt tttcaacatt tccttatcac ttatcgttaa ctgatggaac taagttttct 134040 ctaaagtccc ttatgaataa aattgctaga cattgcaaaa ctct tgac 134100 atgcttcagt ggtgattatc ttcctgatta atgtttacag tcaatctcaa gctctataat 134160 ggactcttaa aggctgtagt agttttctat tgcttccata acatattacc acaaacttag 134220 tggcttaaac aatacccatt tattgtccca cagttccata tgtgagaagt ctgggcacac 134280 catggcccaa ctgggctctt gcttagagtt tgcaaggcag aaatcagtgt tgttagggcc 134340 gatg aattttcctc caagctcatt ccagttgttt tcatgaactg agttccttgt 134400 cattgttgga tccc catttccttg ctggctgtca gctgggagcc agtttttgct 134460 cctagaggct atctgcattg catctcatgg tttctgtgtg cccccttcca gcaacaagat 134520 tctatgtacc cccttccagc aacaatattc tatgtaccct cttccagcaa cagaagatca 134580 agtccttttc aagtttctag tctctctgac ttccccttct tctc attctgcttt 134640 tacaggctca ggtgattaca tcggtttgtg cagataatcc aagataatct ccctgtttta 134700 aagccagtgg gttagccatc ttaattacat ctgcaaaatt ccttcacagc agtacctaga 134760 ttagtgtttg aataacccag gatggtaatc ttgcggggga tcttttagca ttccatctac 134820 ccagtctcat cagcaacact ttgaaatatt gtcgttgagt gatcatttct gtggccggct 134880 gatttcatct atacaagtgt attcttttta tttgccattt tataggataa tattttctga 134940 tcttaattcc cagt attaaaatta cttgacatag aaat catcatctgt 135000 tgcaaaaaag aatt gattggttga atggggagat attt cttttctctt 135060 cttctgctca ggtgggggca acttttgggg gcagatgagt tctgttgcca caaaagttat 135120 atagcacatt tggtttgcac tgaatcagcg attctcaatc atgc tttagaatta 135180 aaaa atcttcaagt atcaatactc agtccctatc atcc aattcatcta 135240 tgataaagcc agagcattga tttttaagtt ctgcaagtga ttctaatata aggc 135300 ctac tgatatgttc caaacactct attttggaga taaagaagtt gaggctgagg 135360 actt agtcacataa agttccataa ctagtaacag acagaagttc tgtcctacaa 135420 Page 93 715825 ‐ Sequence Listing.txt aaaaaaaaaa tgct ttaattgtat gtagagttca gtgctcagta attatgtaca 135480 aagtgagtgt tgagacgatc tggaacaccc ttgc tttagtagga agactatttc 135540 tttctactac tttaaaaaat tatcagatct tgcaaaataa ctgtatgaag gtctcttctc 135600 agcagctttg gcctgccttg tgagtaataa caga tctattctac actaactagg 135660 gagctggccg cttggacttc tactacctct ctgtgttcca gagcttcatg gtacaatgca 135720 gtagccacta gccacatgta aaac acttgaaatg gaactagttt caactgagat 135780 gtatgtgagt gtaaaaggca tactagaatc aaagatccag tatgagaaaa aaggtgcaaa 135840 atatctcatt taca ttgattacat gatgaaataa tatttgaata tattgagtta 135900 aataagatac attattaaaa ttaatatatc aatttttaac ttttttaatg cagttgctag 135960 agaatttaca actatgtatg tggttggcat ttgtggctca cattatattt ctgttagcac 136020 aggg agtattttct attaaagcta ttaacaatga atggtccaag ctat 136080 tacacctcct ttgatcctga agagtgaagg ggtacactgt aaacttcctg gagatgagac 136140 atgatattga tctgccctgt gtttgccatc tatctggcag ccagtcagtc tggccaaata 136200 gacttctatt tttacataga agcttaaagg aggcaggata atgccccatg tcatggagag 136260 agcacactgc atagctcttg agtaatgtac ccaaaagtag accaggtgct ggtt 136320 ctaaggcata gcgataaata ttacatccct tgagcaatgt aatacagccc ttgaagaaac 136380 tgccatgtca gcacttatga attatcactg tctttgacag gccctatgca ctgaaaatat 136440 tatggtgtct acctctcttt ataattcaca tccaaatatt actctgtctt tttcttgctc 136500 cctgtagttt gttctgattc actgctaccc tgattgtgtg tttagtttgc caca 136560 attgaagaag catgggaaag taaaggcagg ccttggaaag atcaagcaca gttcgaaacc 136620 ctacccagaa ttattctgtc tgtgtgagct tgggagattt cctc tctgagctcc 136680 tctaaacttc cattttctca tttgtgaaat ttct cttgcaaggt ctgtctgagg 136740 gttgaatgaa ataagaaggt acctggcaca cttatttttt gggtagatgt tgtagtgaac 136800 atctactctg tggcaagcct aatt gttaggatgt aatcgtgagt gagacacagc 136860 ttcc agctaagaga agagaaagac aaggagcctg gtaacgtcgg aata 136920 aatg aaaggcagct attattacac tgcacagtgc aggatttggc ttataacaaa 136980 Page 94 715825 ‐ Sequence Listing.txt attttagaag cagg tgagggaatt gagacccata gtgattaaat gactacctga 137040 gtcaccagct cggacaatgc tgggctgatg tcaggttacg ggattgctga ctcctcctct 137100 agtaatgcct ttcctgggag atcacattgc ctcactcttg gtttcccaac ttgtttacct 137160 tcaaagaata actttaccat gttggactcg ataaaaggaa agaggggttt attt 137220 ttgctccatt tgttattagg gcatgctagt aactaactgt ctttgaaaac ctacgcttct 137280 gttaactcca aagaaggcag gaatacatgc acttctttaa gatataaaaa gtatttagta 137340 aaat tattatagta atcattgtta atct caccaagata atgaatgttt 137400 ttgtttgaag acttcactgt atgagaaatt gtctcctata ccttatttat ctccttttag 137460 attaggtaaa acaaaatttt caaatttgag tctgaagaaa attccaacat ctttaaattt 137520 gtttaaggaa cattttccat gatctatatg atctatcata gtaatttaaa gatt 137580 ttagaatgag ccacgtgtag aaagagaaaa aaagtagaaa gtcaataaga ggtttcattt 137640 tttt gttttggaaa aaactacttg gtagggacaa tggtgtaaag taagatataa 137700 gaaggaatat actgttcaaa taagcggcca tgat tttctctttc atgtaacaat 137760 cacatctgca ttgtgaatcc gcac caagtgaatc aagcttagtg agttgacaaa 137820 catccacagg gatagttgcg gggaggcatt ataaagtgca atgtggtcct agtgaaacag 137880 tcgt tctttgagaa agttccactc tgaatagaat aacggtgcat accaatatcg 137940 gagtatggcc aagcatttgg ctactgacat gccccttctt ctttcactcc tccataaagg 138000 aagagacaga gactcaggtt cttgtaactc agttgccttt tttgagttct cccaagaaaa 138060 actt caagccaagc gtcttgtcac tgggatttct gtatctaatt tttagttcta 138120 gaaatccatg atttcacaaa acaaattatc caaacctaac gacaaccaca tttc 138180 ttaaagtaga cgagggagga attagcccct aaagtatttc ctgcacaatt cact 138240 atagaagatg tgcc tgtacaccca agcacaaata ggctgtatta ttgccttatc 138300 ctaggagata tacactttac attatgatgg tccttccctt tcctggacct tcatatgatg 138360 cttg atttaggaat agggtcttac atattgtggc tggcgaagag cacatttgct 138420 gattgctcta ccacatgcct agatgtcctc ttcatgatat ataaatgagg gtccctactc 138480 tacc ccataggaac ataataaaac ataaatagtc tatttgttac tactaccaag 138540 Page 95 715825 ‐ Sequence Listing.txt aagacttcag taagtgtaat aactaaccct tttggataca tgcagaggga aatg 138600 ctttaaataa attatctcat ctaatcctga tttttttatt aaaaagggaa aatcttatca 138660 tatgaatatt agagatgagt aggt ttggtagagc ttga acctagccct 138720 ctgtgactcc aaagcacatt cacttaaccc caagcccacc ctctctgtaa atgaagatta 138780 atgatagcat ctgtggtaga agctaatgtc cctg tatc tttcaatgat 138840 tattaactaa atgtgatcag ctgccagtgg atcagatgtc atcaaataaa atcgagtgtc 138900 cagggtttac tcaacagtac tgtctcttac attttttatc aatgttagta gattgcttaa 138960 tctttgtacc tgttacctca catgaagcct agatagcatc agtcccttcc ccagccagtt 139020 tgtgctgggt tcagcttctg gcttgtgaat ccagtcagtg aattaatgtt ggtagcttaa 139080 aaacagccct gagagaggta tttacatcac agaaattggc aaatgataca aatcatgacc 139140 ttaa attccaggga gacaggtgtt aaacatttac cagtacacca atga 139200 ttcaaatcgg gacataataa ttgtatttct gaaggtaaac aaatgcacac tgagtaccct 139260 tggaaaaaag caaccttcca cagatacaat cacacctaag aagt ctttagtgaa 139320 ttttttgtcc ttct gcatttggga ggacctttta caacataacc ataatgattt 139380 tatatgtcat ttgaaatttt aaaaaattac tttatttgtt catttttgtt atgaaagcaa 139440 atatgcccat catt taatgttttt gaatgtaagt gcagacatat aaaccataaa 139500 atgtatatac tacc agtagaaata aaatgcaagc cacatatgta atttaaaatt 139560 ttcaactata gtcatgcacc acgtaatgac ttttcaatga tggactggtc ccataaaatt 139620 ataaaatcat gtttttatga catcttttct atgtttagat atgtctagat acataaatac 139680 ttaatattgt ggtaaaattg cttatactat tcaatagagc agtaacctgc tgcacaggtc 139740 tgtagcccag agcaataggc tatcccatat agcctaggtg tgtagtaggc tataccatct 139800 gtgt aaatacactc tgtggtgttc acagaaccat ggaattgcct aatgatgcat 139860 ttttcagaat gtattcctgt cattaagtga tgcatgactg taatcacatt taaaaaataa 139920 gaaatatttg ttttaataat ggattttatt taattcagca gttaaaaata tgatttcaac 139980 tcaa cgtgaacatt atcaagatat tttgcatctt ttcttcttgt actaagcttt 140040 caattctgtg tatattttat agca catatgaatt tagatgctaa attttaatca 140100 Page 96 715825 ‐ Sequence Listing.txt cttg attt cata aaatgtaaag cttaaaaagt gggttcatat 140160 atccaatctg ttatagactt acatatttaa ttaaattaaa tttaaattgt cattgaattc 140220 ctcaattgca ttagccacat tttaagtgct caatagccac atgtgactta ttgtaacata 140280 attggtcatt gcaggtacat accatatatc cttattttat aaaattggaa acctaggctg 140340 gatgtggtgg cttatggcta taatcccagc actttgggag gccgagacgg aaggatcagg 140400 tgaggccagg aattagagac cagcctgggc aacacaccaa gaccttgtgt ataaaataaa 140460 caaataaata aaaatagcta ggtgtgttgg cacatgccta tggtacaagc tatttgggag 140520 gaag gaggatccct aaag agttggagac tgcagtgagc tatgattatg 140580 ccactgcact cccaacctgg gtggcagagt gagacccatg tctcttcaaa aagtaaaaat 140640 acaaataata ataa ataaataaaa ttggaggcct actatatata caactcccaa 140700 aagtcttttc ccccctcaca acat ttaaaattcc catcctgcat tccctgctgg 140760 atctccaaga ggagagaaat ctcagcaaaa gtagttatat caaaactgtc tgtgagcttt 140820 ttcttcctca ctcataggaa ggaaataaat tcacataagg ggat ctgaccattt 140880 ttat catcaccata aaaagttggt aacaacatga actctgaaag caagctgttt 140940 caatgcatgc ctggtgctaa tgaaaaccag cagttttaaa tgcccttttg cttc 141000 ttcctttttc gtat tattagaaaa gcttcaccaa ggagatcaac tagatataat 141060 atat ttcttagtaa tcaatgttgg catttactct tcccatatat taatttatta 141120 acatcatgct tctaaggatg ctttaatcac ttttttaaaa aaaatacttg atacaaatta 141180 gagggtgtta gttattttag gtggtgattt gttttgtttc tgcaaaatta caaaccagat 141240 atgagcatat tattccctgt gtggcttaat aaactgtttt ttcttttttg agacagagtc 141300 tgtt gccaggctgg agtgcaaggg ctcg gctcactgca acctccgcct 141360 cctgggttca agcgattctc ctgcctcagt ctcccgatca gctgggacta caggtgtgcg 141420 ccaccacacc cagctaattt ttgtattttt ggtagagacg gggtttcacc atgttggcca 141480 ggatggtctc aatctcttga ccttgtgatc cacctgcctc ggcctcccaa aatgctggga 141540 ttacaggtgt ccac gcctggccaa tacactttta atataatttt tgataaaggt 141600 gttatggaga cttgtcacca aatagtctag tcttcacatt aaattcacat gatactcctc 141660 Page 97 715825 ‐ Sequence Listing.txt atctctattt agctctctct cacctccagt aatgacctcc cttgtctctc agtctttggt 141720 ctcttacctt cagcttccca ctagccgttt ctcacatttc caaaagtctt gtaattgcct 141780 taaaacacca agtatccaaa gcagtcctat ctcc tcctgctaac caactcagat 141840 ccccaaatcc tgatttcttt cact atctctcatc cacacatact cagttatttg 141900 acat gtctctatca tctctcatat ccaatcatca ccaaatctta tcaatacttc 141960 tcagtgatat taagttaaga agtcatgaag ggcggctgta ccctaaggaa aacccacttt 142020 tgcacaaatc tgagtttctg ctga gttcagaatg ctgttttaat ctggtcctac 142080 ctcgccaatc taattttagg cccttttatt cgtgaatttg aaccttgttc tctattcacc 142140 agcttcctca gaatattgtc caaaacatac ttca tactcatatc cagaacattt 142200 gctctgagct tttaccatac aagttcacca cagtttctct cccttttcca tatccaccaa 142260 agccttatct gtcatttagt ttta agcccttcag tttgatagct gatttttccc 142320 tagtctgacc ttctattttc gggtatgctc cttcttttca cagtttcatg tgtttgtact 142380 gccttattct tgaagaacca ttattttgat tgcttttgca ttaatctcca tagtgccttg 142440 ctcagtgtta gcaggaacta gtagtttaac aaatacttgc taattctaaa ttaaagagca 142500 tgaaacatat tgttttcttt gcctggagtt ggttatagca aaaa agtattatat 142560 ctaaccttca tcttttctca tatg aactgtttta tagccaaaga ataagttagt 142620 atatcatggg cctaattatg taatttggag gcctcctctg ctgggcagtc tacagattta 142680 aaattcatgc cagctgcatt acgctggttt tgaacttgct ttttcttgag gggg 142740 caaa atgcctcagg ctttgagggt agaaatggtg tgagttccat tatgcaagaa 142800 tagaacccca ttttttaatc cctcctgctg aaaatcttgc catgaggcta tagccaaaga 142860 atgtgtaaat atcaaaagaa atttagagag ggattttccc taggaaaata ttgcaagctt 142920 aaaaaaccca gtgggctaag gtccaattta gtagattcct ccgaacaatg ccatcctcta 142980 ttgt tacagaactt acag catttgagta gactcctgta cctctgggtt 143040 taca tgtaataagt acct gggcaaaaag gcag aggggaatag 143100 agggactttc ttattctcac atctagtata tcattacatt gtaatgttag ataacattaa 143160 agttccaaac ttcatgtgtc cgcactctga cgtttcctag ggacattttg tctcagctag 143220 Page 98 715825 ‐ Sequence Listing.txt aatctaatag agaaggattc cctcatctag aagcttccat atggggctct gtgaagatga 143280 tgtggacagt tcca attgaatgtc acgtctcgtg gcctggctca tgtgagggca 143340 ctagagagag ttctccagag gagtgcagat ggggctactt ttggaatcat tcccactgag 143400 ccaacatcag tggaagagaa gagt tagattctaa taaagccctt atcttctgct 143460 gaatccatcc acattttttt atcctcctcc tggcccctgc acttagttag gtcc 143520 ctatgcagtg ttccaggcgg cagtgaactg cattcacctc ctgtttggga gcatggcaat 143580 tttaaatact tttttctgct gtaagagtat gcaaacagat ttctggttaa ttttgtgttg 143640 aggattcttg tttt gttttgatag agcacattct atggacatat gttcagcttg 143700 taaaggaagt gttatagttc cttttttttt tttttttttt tttttggaga tggagtcttg 143760 ctctgtcacc aggctggagt gcagtggcgc gatctcgact cacttcaacc tccacctccc 143820 tggttcaagc gattctcctg cctcagcctc ccgagtagct gggattacag gcatgcgctg 143880 ccatgcccag ctaatttttg tatttttagt agagacgggg tttcaccatg ttggccagga 143940 tggtctcaat ctcctgacct cacgatctgc ctgcctcggc aagt gctgggatta 144000 tgag ccaccacgcc ccacctagtt ctttatttgg tgaa ttgc 144060 aggcagctgc tttcaaaagt attg gaggaaggtc atcttctatt caactgaagc 144120 aaatgccact tgtttgtggc atctgccagg catccttgag gaag aggtgacttc 144180 agag gatgcagcct tccgagaaat gcaaacctgt tcacattctt gctcagatgg 144240 gaagcagaaa aggctgcgtg ggaattgggg atttactgtt atactctggc attggaatag 144300 caggtgctac tggaaacttc tttacctgac actaagtgtc ttgggagata acaagtaaaa 144360 ttaacacagc ttct tcagtgcttt ctccacttaa aaagaatcag gctgggcacg 144420 cata cctgtaatcc cagcactttg gaaggccaag gcgggtgggt cacttgaggt 144480 caggagtttg agacaagcct ggccaacatg gtgaaacccc gtctctacta aaaatacaaa 144540 aaaaattagc cgggcgcggt ggcgggcgcc tgtagtccca gctactcggg aggctgaggc 144600 aggagaatgg cccg ggaagcggag cttgcagtga gccgagattg cgccactgca 144660 gtccgcagtc ccgcctgggc gcga gactccgtct caaaaaaaaa aaaaaaaaaa 144720 aaaaaaatac aaaaattagc tgggcatggt ggtgcacacc tatagtccca gctacttgga 144780 Page 99 715825 ‐ Sequence Listing.txt aggctcaagc aggagaatcg cttaaacctg ggaggcggaa gttgcagtga gctgagatcg 144840 tgccactgca ctccaggctg ggcaacagag tgaaacaaaa aaagaaaaga gacagaatca 144900 aatgcaaagt aaatatttag ttaccaacag gatggcattt ttagcctata actttttttc 144960 agccttttaa tatatttctg ctggaggttt ccagctttga agcc tgttcaccta 145020 ggagtaaagg acattgggag ggagagatgc tcagtggttc tcatttgcaa agtagacgag 145080 gatgatgaaa ggccatcagc cctt ccaggttagg aattaaaaac atgaatgttg 145140 taaaaaccac aactcatatt tatttgaaat aagt gtgagattta tttgaaatct 145200 cacaaagtgt tatt tgaaatctca caaagtgtga gatttatttg aaatctcaca 145260 atgtgtgaga tttatttgaa caaa gtgtgagatt tatttgaaat aagt 145320 gtgagattta tttgaaatct cacaaagtgt gagatttatt ctca caaagtgtga 145380 gatttatttg aaatctcaca atgtgtgaga tttatttgaa caat gatt 145440 tatttgaaat ctcacaaagt gtgttcatct gcatgtttct cacgtgaaat ctcacaaagt 145500 gtgttcatct gcatgtttac actcaatcct atgaacgact ccatgaagta gtgtatgaag 145560 gagagttcct catgcatgtg gatttgcaca tggggattca gatacaagaa gacaatttag 145620 taga gatgtgcttt tttaaagaaa tttttaagaa tacaaaatta tatggaacaa 145680 aaaagatagg tcctctgctg tctagaaatt aaagtacgtc aagaatttta tccctatgta 145740 gaattacaca gccattgccg ggggccacat ctgtaggccc atggaaaaaa acatctttgc 145800 tcattatttc agcctgatta gggataccat gaagggctat tccattaggt caggtttgca 145860 cagtaataaa aatgaagcca gtagaggatc tcgtggagct cctggtatga tgataagtct 145920 ctgagtaact tgtaaatagt gcaattttat ggaaatgttg cagctaagct tagt 145980 tggcattagt tgtcagacac agct ctacaaaagg caatacgctg agttcatttt 146040 caaccagccc aaacttgcct cagaagatcc gggatgtgga caccctggta tattttttct 146100 agaaaagctt atttccttcc tccagataaa tggt ggtg ttgtgctgac 146160 agaagtgttg atctactctc tccgttagac tgaagggctc caggtgtggc cacactgggc 146220 ttctaaatgg ctagcaaagc cgca tccctcttgg tgtctgaggt gttcacattc 146280 ctgggtcttt cagatctgta ttcctcatga aaataaaacc tctctacgac acactgtgtc 146340 Page 100 715825 ‐ Sequence g.txt cttgtgggtt tttagtttta ctagggagtt tttgtttcct tccc tccttctttc 146400 tgcttccctt ctagttaaac ctctttagga tggctcatta gcaactcgtt ttgagtggtt 146460 tgagctcttt tgttcactgg gatt tatgaaatgt tactattacc gtta 146520 tgtttttcct tttatggcct gtccagctca aggccccatg ctttctgata ctgctgataa 146580 ctat ttccagatca aattaaagca aaccttactg gccctgttac tgaagctgtg 146640 catgggggtc gtttgctgtg aggtgtttct ttga gccagggtat gaacatctct 146700 agtgttcatg ttatttcctg agactagcac tcacgggaag tagaatttat tacaacctgc 146760 agtt catgaaaagt aggacaatat gagactctgg ggcagtgaaa gacttaccag 146820 gattccttct gact cgtcagctca ttcatgtctt acccagtctt taaacagtat 146880 ttcatgataa tggtctgctt ttaattgctg ggctttacct tacccttttt gtgattgcag 146940 gtcctacagg tatggatctc tggcagctgc tgttgacctt ggcactggca ggatcaagtg 147000 atgctttttc tggaagtgag ggtgagttct gcttttccat ttccaccctc agtgttttga 147060 aacaacactg attc gctacatcca agttttttgg atgattttat taaaagatgc 147120 aagttttaca caaa aaggaaactt gacttagctt taaaatcaga aactagtagg 147180 acttttctgt ggatgtttag gaggaatgca gtagtcagtc aactttggca tctgatgttt 147240 tcatatcaaa aattaatact acaaatcatg ctgaggacat ttatgttgaa gacaagccag 147300 gtctcttgtt ctcaggcttt gggagagata ttgaaattac gggt tattagctta 147360 ctgttcactc agctcatctg tgactaagga tatctaatct atttccagag ctcagaattc 147420 aggcttgtta atcatattct cagagaaaag aaattgcagg atga atttcacttc 147480 tcactctctg ggtgattacc atttggctaa gttgaggaaa gagacacctg aaatagttga 147540 atgatatacc cagaaattat gagcttcctt ccccatctct ctcc ctcccttttt 147600 tatatccctc tccttgtaga gaagtctcaa tatgtttaaa ctatgtttca tagcagacct 147660 aactaaaaca aggaagagta atagaaggga aagggaagag ttct gtcagaaaga 147720 aaactgtgct ctctaacggg tgggagactt tttttttttt aatgagtact tgatgttttt 147780 ccttgcctgg gcttctacag aagaaagaaa gaatatattt ctcccatgct atgacactga 147840 atttagttgt tgctttaaga gtgtcagact ccccttctca ccattcagct catgttggaa 147900 Page 101 715825 ‐ Sequence Listing.txt aacacagttt aacagcagac ttagcgcctt aagatgtcct ccctgacctt ctagccaaaa 147960 ccgt agtagtgagc tgctgagggt gaccacagtc acttagaaaa tgagaagagt 148020 aaaatatgtt attttatctc ttaaagcaat ttaaaaatat ttatagaaaa taat 148080 tgttggaaat attttttggt ctctctggcg ttataatgtc aacattatgc aagtcaaaca 148140 gaat tgcaggctcc gcag cttttcccat ggctggtttt agaccttggt 148200 tctgagccaa agaattgcag tcct ctgctgttcc aaagtcatgg tggcttaatc 148260 tctcgtttct tcattaaggt gactttcact ccactgggca agatttgagg aatttaaaaa 148320 acttgtgaaa gtat ggcataggaa atctttaaag aaaattaaaa atgcatcccc 148380 agctgagaga ttagagctca aattacattt taga aagtctgcaa ggagcatctg 148440 tttcagctgc ttcgacattt tactaaaact tcct gagtgaagag aaaacatcac 148500 tagttgcttt taatgtttgc tttttgtttt taat agttttgttt gattcattta 148560 cagg gagagcagaa tataagcaaa tgcaatagtt tatactaaac acaaatcaca 148620 tatcctacca gtacttacgc ataagaagta atttaacaaa gaagaacatt tttgtctctt 148680 ttttttttgt cttattgaac taaccaatat ttctttttcc tttggaatat gtgcatattc 148740 cagaatcctt tcttaaaatg gtctaaggat tggg gcatgatgtt tatgtaagaa 148800 ggcatatgta agcacgttcc agtgtgtgtg tgcatgcttg gctctgtgtg tgtgtgtgtg 148860 tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg ttctagttct ggccacttat ctaatgaatg 148920 ggttcatggg ttcagccaaa gttactgcat aacatgacat gggtcagtct cagataatat 148980 ttatggacca tgtgtttgtt tttctgccag gtctggattg tagccaaatc attttatttt 149040 tattgtgtct cctattgaat aaggcagact aaaaatatag attaaatttt taaaaagaaa 149100 agatactact attgaattca gtttgttcag tgaaagatgt ggcattgatg ggtaagtgat 149160 cttggaagca tcacctggag aaaagtcacc caggagctgg tagaagatga cagacctgta 149220 tgcgtaggga agggtagcac ttgagcaggg attttcttgc ttgggcagat gagcaattag 149280 actg gccctgaaag gatttttttt tattaaatct aattgccctg tgggaaattt 149340 aatgagaact aaatttgaac agtgccgtta ttgtgttagc taaagtgttg taatagatgt 149400 tttctgtctc tcatccttaa tatgaagttc tcatccttaa tatgaagctc tatatctgct 149460 Page 102 715825 ‐ Sequence Listing.txt cctcaaagcc agttacatag tctagaggag aattttttat tccaaaatca ggaatgatcc 149520 acaatgcctt gttttcaaag acat ggttgaccta tcaactgatt gtatcaaaat 149580 tgctgctgct ggaataatgt tgctaatgag aaatgtgcat aaagatctaa tggatataag 149640 tattcttcca aggagtgcct gttataaatt aggtcgtata tctctactat ttcaatcagt 149700 ctacccttga cctt tgacctcagt aacctaaggt ggaagtaagc aagcccctgc 149760 cttgtagttc agtctagctg ggacatgagg aatgtcttga aattaatgag agcctgtata 149820 cctttaaagt ctagattgtg agag aaatggtcaa gatgccctga aaaagaatag 149880 gtgg actagaatag ttaattcaac agtg tactgataat gagc 149940 ttcctatttt caaagcctgc acctatggct atgaggaata cattgattct tccctcaagg 150000 aacttttcat gggttaataa atcaggcatg tacaccaaga attacaatat caggcattgt 150060 atattaacta tcaaaatggc caca ctttatagaa gtgatgatga cgtgagggat 150120 acctcagctg tggtgaatta cagcttcatg aaggaggttg acattgtttc tctagagact 150180 agaatgtcag gtttaagatt ttaaaaggct gagaagaaca gaaggctatt acaggaataa 150240 cttatgtgat aaagcaacaa cataaacaga caga tgtagatatg agatgtctat 150300 ggacaacaat tcattcactt ctag tcaatggatg gttctatttt atgcatttaa 150360 cattcaacaa cttg agcacttact tcgtggaagg cataggatta atttggccag 150420 ggtgtgtggt acataggtgc tatatttgta attattccct ttggaagcaa acttaggtca 150480 gtaggtttga gtcaaattat agaaggccca gagatagcaa aggcattatg gaaaaggcaa 150540 gacttgctgg gcccttgaaa aatcggtagc atttggagag gaagaaaaga aagaggaagt 150600 gtatgccata tccagccagt cctc aatattggag gccagacaaa agcgctacct 150660 gcatgatgga atagtgtgtg tgtgtgcata atat tcatatgtaa catatatagt 150720 atctacatgt aatattgata tataatattt aaca tatttatatt tgtatgtgtg 150780 taatacatac actatatgta cacatataca tatacatgta tatatatgta cactatatgt 150840 atatagtata tgtatgtgca caccagtgag gtgtggcttg caggcaaagc acataattga 150900 catcactcaa attctgcaaa aggtgttata tcattctgta ccattcaaag actt 150960 gaga tgccacatcc taagggaacc aagagcccca aaataatttt ttctgtatat 151020 Page 103 715825 ‐ Sequence Listing.txt tttgaacatt tttcataaac ctatgcacac tgacaaaaca cttacttgaa aggaaagaca 151080 cccctgttct cattgctatc agacagcaac aatttatttt ttaaaataaa ctctattcca 151140 ccacagttga ggttccacag agctctgaga caag acatgtcaga tatatttcac 151200 acaagtatta gagtcatggt ttcagttagt aaacagtaat gaatgcatct gttaaatgtg 151260 ttcaagaatg aacacttcaa ggctttccat tcacagtgaa ggtggggaaa aaagccacag 151320 tgat tgctgctgtc ttcaccataa tccagaggca agaagaaatc ttatggtgtg 151380 ttctagtgca atggcctgcg tccatgtaca tcagcaatcc tctgtcccct tgtcctcctg 151440 atattgcaga atttatttga tgttggagtt cagcaggtca cagcaagctg gattaatcta 151500 gatggtgcca atgtagataa tgacacataa aaagtctttc cttt tattaagtca 151560 ttttacagat tcaaggagga atttcatgta tttatttatt tattcattca attttgcatg 151620 catgcattta ttcatttttt tgttttagag ataggaactt gctatgttgt gcaggcccca 151680 aacagttcta ctagcttcaa acaatccttc ttcagcctgc agagtagttg tagg 151740 tatgagccac tgtgcccagc ccaaggaaga attttgaatg tatattcctg agga 151800 agtc tttagaagag aaaacagaga aataaacata ttgt gatcctctta 151860 taaa gggttttaat ctaggtaata atactgttag atttttactt tgtcagtaat 151920 actagtaata ggataaaagt gaatttgaaa gggatgaatt agaggaggaa gttgatgaca 151980 ataggtcagg agagagataa tgtg acagggatga taaaaaatag atggatcaca 152040 aacacgggga tgttaagaag ttac cagtactcag agtctaatta ggat 152100 ttttgactcg gggaactatc agtgccttct tttccatcca tttctaagtt tctgcatttt 152160 taattaatgt gatcatcagc aatgactcac gtttaatgca tcct ggtgcacagt 152220 tcagcctatt agcactaaag tggcacttgc acagaacaac tctgtagggg aggaaacatg 152280 ctgaggctgg atgacagcag agtgtctaag ttct tttgtactat ttctctgaac 152340 tcctcatgcc tgtgtctacc ctgggtcctg tctg ctcagctctg cagtatggct 152400 gtggtatggc tcaggctact atgcagtgag ggtctacagc aaggacaaag gtctgaactc 152460 cctcctcatt gtagtctctg gacatgtgtg actctatccc aaaaccttga ccca 152520 gatattttgt cattgctaga gtatgtactt actcatggga tacaataaaa tatatgcagg 152580 Page 104 715825 ‐ Sequence Listing.txt atgagttgag aacagcagag ccatgtgctg gtct gggaggttgg ttaggctccc 152640 acggaaaatg agtgacctac ccctacaaag gcag tgat tagatttgtg 152700 ccacagctaa ttagtaaatt gaaggagtgg gaccacccaa gaatactcag gaat 152760 gttagttaaa ttcacacatg ccagtgatag agtatatttc tggtcttccg ccttagatgc 152820 cagctcttac gggaacagag ccagtcctgg ttatataata gaatgtttcc acaccacttt 152880 ggttcagtat cctaaattgt ggctcttgtt atggggtaga caggaatgag gttgacataa 152940 tggt gtttggtgat ggcaaagagt acctgttcat agacacacct ggttgtccac 153000 ctctggctag agaccaaccc aagttcaact gtgcagaagt ccatgttggc ctttactggc 153060 ccagccagcc tctacctgag atcattccct acaacaaggg gatt cctcagtcac 153120 agct tttcccaagg aaaaccatct catgaagaat ttga tgattttctc 153180 ctcactgtgc gtca atgggtttat tactgagagt tggttccttt taaaccttaa 153240 ccttacactg tatatgatat agaactgtag gcaggccagg gtcatcaata aagacatttt 153300 tggggcctct acttggcttg taaccacctg cttatccaca gtactgtgca cctagcttgt 153360 catcaggcag cagc agccacaaca tgca ccttcgtctt ttccaagcag 153420 caggcaatgt ggctccattt taacttttct ggcaatactc acatggattg ttaaataatg 153480 ctgtcaacag tgtcatcttc aaacccaaag caaacttcct catcatctgt agttagcagc 153540 atgaagacgg tgatgatgtg taacataaac acactttgaa atctgatgca attgacccta 153600 cgaagagagt attccttagt gccctgtctg gcaacttctg gacagaccag gaggccttgg 153660 ggcttagagc acttcttcag cctcagctgc aaatccattt gtcc cttgttccca 153720 ggatgaagcc acagtgtttc atcaggtaca tttatcagga atctctgttt ctgtttatat 153780 aacaatttaa cttaagcctc aaccttcaca gtgtacgcat cacatttcca tggaaggatt 153840 gcaggtatta gaagatggtg gatcatgtct taaccacagg ggaaatgttt caggatgttt 153900 ttatagaaac tttcactaac aagcaggaca tggc gtgg gggtaggagg 153960 aagg gtggcatttg ttgtgtttcc ctcttctaaa tgaagttata atgacatctg 154020 tgtttcaaga gtgtggcaag tttggactga gcttgaaata aatacagttt aattggtttc 154080 aaataactga acaaaatgac cattccatgc cctgtgtaat aaaatgttat agaattaaaa 154140 Page 105 715825 ‐ ce Listing.txt cttattagac gttaaaatcc atgaaggata ttttgctgga tgcccatcct tcagcattct 154200 gatgaggatc ttcgtgtatt tgttcaatga ataagtgaat cagcagctaa atcctgacct 154260 ttgatttcct cagttctctc ctgcaattgt tgct ctcatctcca gtcctgagca 154320 aggcaggagt tgaattagta tccccttata gtgggagggg tctagaaata gctgtgccac 154380 tttagaagct aggctttgtg ggcttttccg ggggatggaa tgatttcatt ttcctgcttt 154440 ctactccaca taccaccaag atcagaattc tgccctaaac actaatgtgt gggagcctga 154500 tgtcctgcct aagtcttgtc aacctctttc caggtgactg aactccgaac cccatgcacc 154560 agtcactggc caacattctg cattaagtga cccggtcacc cagcaccatc cccctgacac 154620 tatc tctacaccac ctgcctcctg taaa tctcctcaaa tattgacaga 154680 cataatgata cctgaagatc ccaaatccaa attttctttg cccctttgga cattgaactt 154740 tagattacaa aagaccctga ctagggatcc tagc tgagtcaatt ttcttagccc 154800 cattccttaa atatcaagtc tttctaattt tccaatgaga gcacatgaaa ctctcaaggt 154860 taaaagtcaa tttatattaa taaaatcttt aatttcttga tttctgaata tgaaaaaatg 154920 atactttgtg tattttttaa ttttttggca aaaccttcca aatttgtgga aagagaaata 154980 atattgacta ctggataacc atgtgctatg tgtaaatatt aacggattca ccttagtggg 155040 cactgacttg atgatgtttg ccacattata ttttccagag ctct cccaaaaaat 155100 gagaggtcat ttttcagggg aggaccattt tgtgtttggc ttag taat 155160 ttcttctcct ctacatgcca ctgacccact gcatccctgg ttggagcaag aagagccatg 155220 ctttccttaa taatagctaa tggtgaaagg atgtgttgta acaagagcag aggg 155280 aaacaggaga aagacagtca gttgaagagt cctgccctgt gtcagggcac cgtttggcca 155340 cttg ctaggagtag aatatagaaa gtacatgaag actc agacagctct 155400 ggctacgttg acaaactggt atatcatggt gcccaacttt ctttgttagc agca 155460 tcataccctc tagtatttgc tctgaacttc gtaagcacgg ttgactagct ttcttttcct 155520 ctgcagttat cattcagact gaatagtttc taagaggctc ttaatgagaa atagaaggaa 155580 gtaagttaac gcat accttggcca tatttgcttg tgat gtgtatacta 155640 aagccattat gggtgtgaaa ggcaaaagta taagtgctcc tgac ctggctattt 155700 Page 106 715825 ‐ Sequence Listing.txt tgtcttactt ctatatttga ttgctaaaaa tatatgttct tgggtcaaaa aactcacttt 155760 aagggaaaaa aatggaagaa tattaataac caaaatagaa gaatattaag aactttaaca 155820 tgagatgtat ttagatcaaa accatctctt tttt tgcgggtgat ttctccaaca 155880 tgtttagaac gcta ttcacccaaa ggtggaaact tttgatgttg gggaatacca 155940 ctgatgcctt aaagcagagg gtaaaaggaa aagactgaaa ttccaggcta aaatgaggag 156000 agcatggcca ccactgagcc caaggtagca ttcaataaat actatataaa ttactgattt 156060 atttctacag ttggttgata gaagcttact atgatctgcc taagggtgca tcaaattcct 156120 ctggtactta tcctattctt gactatcact tccttggggg cagcagttaa tcaggtagag 156180 gcttatcctg tcaagagagt agct atggaggaac tcgctgggag gagaagctgg 156240 tcctcagaga tgcttagggt ttaggaccag taagaggcag tctccacacc acccacatct 156300 gattcttgtc tccttcttct ctgctgtggt caggagaaac agtttagatt agggatttca 156360 gagcagtggt gttgaacttt gtcaaaactg catttgaatc ccatttatga attgtgtgat 156420 ttttttaagg ttgagttccc cagaagtagg atgctgagac aaggattcct atgaaagtga 156480 agaa aatggtccag ggagaaagcg ataggagagt cagaaaatga gacggggaag 156540 gtaaagaaac cagacaagga tacaatatca agtagaatcc aacagtggtg tgggtgggta 156600 gaagtatctg tctcagcaga ttttgagttg tccagattat cctcagttgg tggttaaggt 156660 taaatttgca tcctcacgag gatgcaaatt cact atcagttgtc caagtgcagg 156720 taaagctggc tccagcagcc tgagggcagc cgacagagag acacgggtcc tgggtgtggg 156780 acca cacatgaagc ctgcatgtaa aaaaaaaaaa gagg ggctgggcgc 156840 gatggctcat aatc ccagcacttt gggaggccaa ggcgggtgga tcgagaggtc 156900 aagagtttga gaccagcctg gccaacatgg tgaaacccta tctctactaa gaatacaaaa 156960 attagctggg cagggtggcg ggcacctgta gtcccagctg ctcgggaggc tgaggcaggg 157020 gaattgcttg aacccaggag gcagaagttg cagtgagctg aggtggtgcc actgcactcc 157080 agcctggtca caac actctgtctc agaaaattaa aataataaaa taaaataaaa 157140 aaaa taaaataaaa taaaataaaa taaaataaat aaat aaaataaaat 157200 aaaataaaat aaat agtaaagtaa aataaaataa agag atcaatctac 157260 Page 107 715825 ‐ Sequence Listing.txt atcaccaaag cactgacagc atctgctaca gtgactttgg tagtttctta cattctctga 157320 gcctcagttt tcttatctct taagtcagag gaaaatgact tgtttaaaaa ggcttcaatg 157380 aggtaacaca agtaaagcat gtattgagat tactacacag gaaaagcagt tgctgaatac 157440 aattagtcaa ctggtaattg gtaataatta tgtaaaattc ttat agggagcgct 157500 atacaattat tatatataat tcctataatt ggaattacca ataggctaat tgtattcagt 157560 aactactctt attgtcctca agttgagtta ttattgcaag ccctgagggc tgaataaaca 157620 tgcaaactaa actgacatgt ttat ttataacaat atatgcctaa aagaagcggt 157680 ttatttgcac aaggaaattt tggaagctac agataatttt aataatgact acagaaaact 157740 atcttgaaga tgtttctaat gtttaagaca taatagcata agcctttata aaatgggata 157800 ctgttatgta gttatagttg tcag aagg atgggtttga tgaaattgta 157860 ctactctagt tcctgtgctt ctaataaaat taaatctgat taatacagca agtaggtctt 157920 tggtgagttg attctgatgc tgat tttcttaatt cttgctcaga tcca 157980 tgagaattaa atgagatagc atgtacaata cctggtatag ttactggtaa gaggttttca 158040 acca tctt tgtttacctt ctcatcaaga gaggaagaac aaggaaaatt 158100 aggttgcttt tttgagaaaa tactttaggc caattacaat tatctgaaag tagaatgaat 158160 ttctaggtta ggcaagacta aaac gtgc agggctgacc tgccagggta 158220 ctctgtatgg aagtacatgg aaatgtatgc ccaaatacag cttcatataa tgat 158280 catacacagt ttccacatga gattatattt gaatgactaa ttcagcaaat aagg 158340 agaaaaccag tggacaagat gattcctaag gttcctttct tcctggtcta tgccctagtg 158400 gaat tgatattcac tggaacacac agttactgct ggagattgag ttataaaaac 158460 attcaaatgg gttactccat tatatctact taggaaattt ttttttaaaa taactgatag 158520 atgttcagtt atgcgaaacg aaaggtattt ctggctaccc ctttatagtt gtgtacatga 158580 ctgcagagcc atcatttcat gcttacttcc ccacattcat gtaccatttt ctcaaaggaa 158640 aattattgaa tgaacttgct agttttgatt ctggggtttg ttttaaacaa ctgatattta 158700 aatccaccta gtcctcttta gctgttctcc taggaacttt aatattaaca aacagctgaa 158760 cttatacatt aaga gttcagacaa tgaattcatt gaaa tgcatggaag 158820 Page 108 715825 ‐ Sequence g.txt tacccaggtg ctagctacac ccaagagcct tttctaaata caaaaaggat tgacaaacca 158880 agcattcatc ctgtctgcgt ccaacagttc ggaatcaaac catgaacttg ctgttcctct 158940 gtttgtggtt agcttgtttg tatattttta aggaagatga ttcaatgcaa gaagtagttt 159000 tatatagtac gttaagtaaa tttcctatac gatatactta atcagaaaaa tatttttgaa 159060 ctagagctca atat gattacaata gttttcagaa agcaaggggc taaatgagga 159120 tttctcaacc ttggcactat ttta ggttaattta tctatggtgg gaggcgtgtc 159180 ctgtgcattg tagcatattt atcagcagtt gtgacctcgt acccactaga taccagtagt 159240 cccccttctc agttgcaaca accaaaacaa ctatagacat tgctaagtgt tctctagggg 159300 tcaaaatggc tcctgcttga gaaccacagt ctgg tagttgcata ttgaactgac 159360 agtccccagg attgttgtgg ggatcaaatt agataaaact tgtttatatt ttttaaaaag 159420 taaaactaat acatatagtt acattacacc tcttcttttc atttgttact catctaagat 159480 tttttgagcc agatgatgga gacccataaa taaattaacc ttaagaggct caaaggtttg 159540 ccaggtaaac aaagagttag aagaaaaaga gagatcatgt cagatgtgcc ttaatgaatg 159600 tgtgtgtaac atgtacaaaa agttatggga accccaagaa agaaaagact ccttttgaat 159660 gaaatcagag aact ggaccataca gttgaagctc tataacagga attaccaatt 159720 aactaattgt aactaaatac tcttttatac atat attcatgtag tttttaaatc 159780 tagaagtagt taaggttcat aattgtcatt tctcagggac gaag tggtatcaaa 159840 tctaaatgag caacttaaga attgaagttg tcagacagct gttaattccc ctttttcata 159900 cctgctccaa tgatagccaa aaca aaaataataa aataaaaacg aaagcaaaaa 159960 atacaactca gatttcacta cgtacagcaa taaatatcag agacattagg taat 160020 aggtcaaagc agaaattcat tcctcagcat caag tggaagaatt aggtctgttt 160080 tgtt gattctaaaa gaaacattca caag aaaacctgtt ttaaactcta 160140 aatctgacac tatagataga tagatagata gatagataga tagatagata gatagataga 160200 tagatagata gatagatgat agatagatat agatagatag atagatagat atag 160260 agat agatagacag atagatagat ataattctgc ctaagtaatt atctgctggt 160320 accaaagaga ttgacaaaga gattcactaa cctaccagaa aacc ttgttccagg 160380 Page 109 715825 ‐ Sequence Listing.txt gtattctaca ttaaatactc attaccaagg aaattccaca taaaagctgt tgat 160440 atat gaaa agca ttttcttctt tctt tttg 160500 accaattcca tgttccaggg agtactcaga ggctgattag gacatgagtt gttagcatgt 160560 ctaa tggttatgag tcacatttgt tttggaagat cacccttaaa gcctgtcact 160620 catgcttgtt tatgggaaat acaacaactt aaacatcagt taacaaatcc ccatgaatgc 160680 atggtcatat ttgagtgctt ctaacaaatg cttcctttca tttctccctt gacagcccta 160740 agaattaaag gctggtagag caaactggga gacatccatg aacatttatt aaaggaagca 160800 taggagagta tgataactgc aaagccagct gtttatatta tgag attaaatttc 160860 atcagtctta aaacctgctt tttaccacta gagaaatcaa tctgccatat ttaaggttac 160920 attaacgtgg aacattccac gtactgaact gtcacatgcc tttaaaataa catg 160980 ctgttttttt tttttaaaat cattacacat gaaacaaaca aggt ggggatctat 161040 tggtatattc aagtttttca tgtgaaaatt tcccccaata ttagtggtaa tcacaatttg 161100 agaa acaaacatac catatatagg cagaactata tatcagtagc ctttatattt 161160 gacagctcac tgtaaaatcc atactatgat tcagtgaaca tatttatgtc ctgg 161220 gttgatctgg ttgccttcag ctttcctcac ttgaaaaaac tatacttaaa aaactgtaat 161280 ttaatgttaa agttaattaa cacagcaaat acttattgat gacctattat ttactgggta 161340 ctattttcgg tgcttgcaat gcctcaatga acaaaagaga taaaaacctc tatggtcatg 161400 ctgcttgctt tagtgagata tatgtgtgtt tgtggggtgg aggacatgaa tgtgaggcag 161460 acaataggct acaaaaataa taaattatct agtattttat aaggtggaaa gagctatgga 161520 aaactgcccc atttgttcct catctgagta tacccaaaag ttgatcttta atattttata 161580 tgagtctcct aggttctaaa tgttagaaac taattaaaaa taaattgaaa ctaaactaaa 161640 tatctttgtg atctctctgg ctagaagcct caggaccagt cctcactgtt tactgatgag 161700 gaagccgagg cccagagaat atgt agccaagatt tcaagcagtt actgtcagag 161760 gtaggaccaa gacacacaac ctccttctct agtgtgtttt tctcaatcgg ttggcattta 161820 acagcaagtg ttttagttga aaaaatttat ttgaaaatct gtttgaaaca tgacaaaata 161880 ggaaatacct tccc tcactgcaga gtggtcctca gcagaaagaa gattttgaag 161940 Page 110 715825 ‐ Sequence g.txt tttatgaatt atgttcagac ctta taaaatcact ctcctctctc cagtggcaga 162000 agcgtggccc ctgactcctc acccaccttc attcatcttt cgtattcctt gaaaattacc 162060 actgagtatt ttccttctgc ttcctgcagc accagcagaa agga tgcgtctctt 162120 gattgccatt acaaatctct ttcttatgct tgtttccatt ctgc acataacttg 162180 gcca tcattcttag agctcctcta aattgtttga ttaaaagatt gtttataagt 162240 ccagagtcag aacggaattg aaaaggcact tatg atggagagga ataaactcca 162300 gtcaaaagtc atggcttctg gactcaccac cctaaggcag cctcactgga acttgctttt 162360 ccaactgtca gtggagtttt agaattttcc tacttgcaag cttgttgtga aacg 162420 gttaagagag attgtgtctg ttatggaatt gtgaaaactg taagttgcag tccacactgt 162480 agaaatctta gttacctctg ccctttcttt ctctagagac aggttgctag tggaatagac 162540 aagtttgcca ttaatttgaa ggttgcatta agcatatatt atgttagtga agttggtctt 162600 ctgaaagttg gaagggacct cagaggtcct gtattagacc ggct gttccttaga 162660 ataagctgga agttttctga aaaatacaaa ttctgaagcc tcatacatag agattctgat 162720 gtggaagatc tggaattgat ggcagcagcg gcccatctgg agccgctgct gtgaagatgc 162780 cggctgtagt gggggaggtg cggctgtggt tgtgccctcc acagagctgc caggtgggaa 162840 gcctgaccct tctgagttgg caggtctgaa gcccagtgct gcac agttgcagct 162900 gcccatctgt gcctctagac atcc ccgtgctctc gggggcccag gaagcacccc 162960 ctgctcctgc aggcttggaa gtgcctgcta tcactccctg gcctctccct gcac 163020 ccagcacccg ctccggggtg aagcaaagtc atggccaagc ctggatgctg tcatgacctg 163080 gtcaggtgtg cacacactcg gagcagtgct gacacaccag ccccctggca cataggcact 163140 ctctggactt tggacaccaa tggg agggagactg agagggcact aaggggtggt 163200 tcagcgcagg cctgcaggcg ccccttggca tgaacagcct gggtgctgtg gatgacatgt 163260 agatggtggc agaaggcaga cctg ggcagaaaga ggccagtccc cagtgaagct 163320 ccaccttcaa gccagggatg gccggaagcc ttgtggctga gctatcagtt ccaggtggag 163380 gctg ggagtgagaa cttatggtgc tttatccagg ccttcccata gccacccatg 163440 gaccaataag cacacccttc tctg atctcataaa atccctggac ttatccaaac 163500 Page 111 715825 ‐ Sequence Listing.txt tcgggcagat atga cctgcctatg gataagagct acccacttca ggtctcctga 163560 gaactgtact gtcactcagt aaagtatttc ttcaccttgc tcaccttcca gttgtctgtg 163620 tatctcattc gatg tgggacaaga actcaggacc cacttaatag caggactgaa 163680 agagctgtaa cacgaacagg gctgagacat gccttccctg cccaccacat tgtaggtgac 163740 agaa gagctacagc cctttgggga gcccagacct cacc gggg 163800 cggt catc tccatgctcc caggcgtcac cacattcccc tcgtccagat 163860 gcagttgccc acggtggaag ccatttgcgt acatcagatg cagccgcagg cttgcatgga 163920 gctggtgcct gtgctggtgc ctggagctgc tcaccccacc acggcagctg gtgtacctgg 163980 acag tggctgaacc ccatgcttac ccactcacgt atccctcatt cgcc 164040 tggcttgccc ttggcaggca tggggtccag gctggtagcg caacccgagc atagcctacc 164100 aggccgttgg cagaacaagc ccattgggcc cgagcaaaac ttgggcaaat gtgccaccag 164160 ccacaaaaag gaaacacaaa agtttccagc tggaaaagca agacctgaag aatcctgcaa 164220 cagaatgatg ctctggagtg ttttctgtgt taggtgtgct tgtttgtttg actaaacctc 164280 caaacatgag tctgaagatt aaccagtttg ggaagccttg cttcagcttt ctactgacat 164340 taaactcctt ctcctctccc atttctgtct tcacttagaa atggaaaccc tact 164400 caagatctta ccttttccat tcagtcaact aggcccttgc acccccatta ctttgcgttc 164460 caccttgaca attgctattg ccaaacatcg gcattaatct attttgacat cttctttcca 164520 cctgctgccc tctagtggaa gtgctgacaa gcagcaaaat atttaactgg gaacagcagg 164580 aaagtgacca gtttgagctg gccagttcac acaagtcagc gcaggtcccc agcatgatgt 164640 ctacagacta cagctatgcc agaaatcgtt aggatggcct gttt tatt 164700 tgcacacaag ttacatttag agcagaactt tgtaaagacc ctggcattta ttcaagggct 164760 ttttaaaggt ttcaaaaatc tacctggaaa acattaccct tgggatattt ttgtttcttt 164820 gtccctcatt ttcttctttt gtcatttacc caaattcttc ttcttgcaaa agaaggtggt 164880 tctttcctgc cttccctaac ctttgaattt tccaaatctt gcaaaaaata aagatatata 164940 tatctttaaa taaagatata tata tataaattct tacagtttag ccag 165000 tcaccaggtg aaaggaattc acatgaactg aaaattgaca atgtaaagga cactgtgttc 165060 Page 112 715825 ‐ Sequence Listing.txt tcctactgtt cctccaagtc tctttgcggt ccgttagtag tcttcttttt tccaggagac 165120 actgaagtta agagagttta agaagattgt agtatgtcac aaagcaagtg gaaaagctag 165180 aact caggtctggc tgatggaaaa cccttatgta ttttttttaa tgtgcttctt 165240 tggtgtttag ttta gtcttccgtg aagtaataaa taataacttg catggtaaat 165300 gttattaagg ctcgaggtac taaatttata gtca ttcagctttt ttttaaatga 165360 atgtttaata atcagtgtgt ctctgcataa atta ctccttttag cagaggaaca 165420 tggcaggaat gcaggtaagt ttgggtggga ggaaaagaca gcaaaagcca cagcactgat 165480 gcaaagttga attt cacagggcag atgccgtata ctccctcaag ctttgaagaa 165540 actaaatagt tatctatgtt aaccaatagg gcagaactcg tactccaaac accgacataa 165600 accgtgtgtg tgttttgtgt atgtgtgtgt cttcccccac agcattctgc acaattatta 165660 accctttttg tgtagtggtt tttcataatt ttatccttga ttgttaatat catggtaagt 165720 gatgtgttat aaatatattt ttccttaagt atcataaaca atctaagatt ggct 165780 gatttttctt ttcttagtat tgcatatcat tattgctgtt agaacactca tacagattat 165840 tctt aactagaatg tatacacaca cacacacaca cacacacaca cacgtgcatg 165900 tacagaactg ccttctttct ctttgatggt agaaaataca gctctctata aaat 165960 ttgctttcag tctcagacat acccttcatt ctctgcatga aaga gcggaaagag 166020 taatacttag gatctggatt ccct gttctctgac catttaaaaa ttttgttacc 166080 ttggccaggt aaatacagtt ctatgaacgt cagttgtgcc tcaattgagc aggcttgtcc 166140 ttcc tcaaggatga ggtatccttt cagctgtatg agctgaacct tgatttgtgc 166200 aatagtttaa gcccctgaat agtcagataa aaatcatgtt aattaaaatt aaatagctat 166260 gatc tggttttcca ctggcttgca tgaatgatgt tttgccctcc tttctgatac 166320 tcagctcaga ggattccttc cattgggttt tctttcttgt agtttttctg gttcataaat 166380 agcctataga caaacactaa actgttacag gtaaaaggac cctagattaa gccttttata 166440 aaacaaatag tcctgtgtaa ataatgacat cttattttat gaat ttgagtttta 166500 ggatgtaggg catgtctgac gcta aaggctgagc tccaggcagc cagctgctat 166560 ccaatctcca cacctggaat gttccaaaaa acctcctgtg ttttctttct gcagctaagc 166620 Page 113 715825 ‐ Sequence Listing.txt actgatgagc aggatttaag aagtacagcc acacactttt tgctgcacgt tttttaaagt 166680 ttgttatttt tgtcatagat tacttgtttt gaatcaaaaa tttttaaaga aaacttaatc 166740 tcccaaattt taaccccctt tcag gattccaagg aatattttta ttttaagatg 166800 cataaaatac tcagtacatg tacaaaggta atgcttataa gaaacttaga aaaaaaaaag 166860 gagctagtaa gattgagaag gggaagaata tctaagctaa cattactaac ctggcaacta 166920 ttataggtgg agca tgaaggcata aagctgaagg cagttaagaa aatagactgg 166980 atttgaatcc tggctctacc tggattagtt ttgtgacctc agagaagttg cttcccttct 167040 ctca gtttcttcat atgtaaaagg agataactat agtgtctaac acacagaatt 167100 attgtgagga ttaaataagt taatacatat aaagaaagtc caaaactatg gcacacaaat 167160 gtttaatata ctat tattgttata aaactaaaga aagagaaccc agaagacatt 167220 cagtttggtg ggattcagat atatgttttc ctttcctcct cctcctcctc ctctccttct 167280 ctaaccccac tatgcttgcc tcccaatcta tccctgactc ctatttttct tcctcccaac 167340 ttaagaattg tcactaaaaa tatttagaag aaaagaaaat gtgcatactt cagggggtgc 167400 tttg ggtaaagtac acttttcagc taacatgact aaca gtaatgggct 167460 ttatggcaag aaaaagcttt tttctcaata aatgggtttt aactttgtaa tggattattc 167520 tctttgcatg ggtaattctt ctggaagatg gaaattggct cgatgataag ataggacagt 167580 tggatttagg gatctagatt ctat catgtatgct tttaggagag aagtttaatc 167640 tgcaaaacct acttgtctta tttaattaat tctt tcaa ttttgtacag 167700 gtgacttgca tgaaagcaaa atgtatgtca aaaa gcagagtgaa gcctcgggac 167760 ttcagtgctt ttgggtgtct ttccagacct ctgctcttcc cccaccctca ccaaggcccc 167820 actgacctca aagggccctt cttgccaggc cgtgaattac gtctgagcca gagggctggg 167880 actacagcca aagccaaatg aaggtgcaga atttaggact aaaaaaagcc tgagcacgtg 167940 ggta tagcagataa atttgttgga gaaatggttt ataaataaca tgaaaaggga 168000 aaggggatag aaaa gctg ttgagagttg ttcaatattt gaggtcagtc 168060 tcaccatttt taatactgaa cccaaaagta atacacactg aaaaaaaaaa cact 168120 gaataaaatt aactacagct gggcttattt atca agacatttgt aagtttggca 168180 Page 114 715825 ‐ Sequence Listing.txt gcaagcattt ttaaacagga tctctattat atgaaataaa tttaaaaaca tgtgtctaca 168240 gtcaggacaa acaagtgaac aaaaacaaag caaaagcaat aaagaagccc catgaaggca 168300 ttatgctttt ctgaggacag tataaggcta ggatactgca gaaactgaaa tacttaggga 168360 tcttattgaa atagttttct tttcctccaa acaaagcaac catctcagag ggatagatgg 168420 gctaaaagac aaggaataaa gtaaacagaa gattggtaac ttgggaggtt tccc 168480 ctttctcttt ttggttttga tttgcttttc ccttgttaaa gccagaaagg tttg 168540 gtccagaact cccaagacca gagggtcagg gaaagccacc ccgaggctgg aagctatgaa 168600 cttatcgcta gtctaaactc cttc ttccctggga gtcctgcaca aatataactg 168660 cctgatcttt ctgtttactg gcaaaggttt cttc gtat cggaatgtga 168720 acttggggaa agatttgggg ttttttttgt tttg tttttttaag aaacagagac 168780 ttgacttatt acaa actcttaccc tggcacaggg agaccacaaa gaaa 168840 acaaggtaag agag aaatgggacc atatgccctc cccggagctg aaccgtgttc 168900 cctgtccacc atcaccttgt cttcccatgc tactactcca ctcctgtctc ttccacactc 168960 tgggtcacat gtctacccct tactgtgagt tataatcgcc caggaagggt aacccattga 169020 ctgagggcca agcttctgat aagtgaatga acttgtcttt ggcc agatatctgt 169080 ctttgccaga gagggctgag tcagggagac taagattttc aaggtcaaat tgtatattgt 169140 ttaaaattgt gaaaatttgc tttgtgcatt gaatctcatt ttcaaaataa aattatgcct 169200 taagtcagat catactgatg cagattctgc agatgttaag aggcttccat gattgtattt 169260 gccagctgca ggtcaggcag tggtggatgg tggtaagaag taacctatac ttttggctgg 169320 gagctgtggt tcatgcctgt aatcccagcg ctttaggagg ctcaggcggg cagatcacga 169380 gatcaggaga ttgagaccat cctggctaac acagtgaaac cccgtctcta ctaaaaatac 169440 aaaaaaatta gccaggcttg gtggcacacg cctgtagtcc cagctacttg ggagactgaa 169500 gcaggagaat cgcttgaacc tgggaggcag ctgt gagcgagatc gcgccattgc 169560 actccacact ccagcctggg cagcaaaagc gaaactccat ctcaaaaaaa aaaaaaaaaa 169620 aaaaaaaagt gacctatagt tttgcagtag aattttgaat tcaaactcag gctttatatt 169680 ttctccaaag gtat catt ttaatccatt ggttgactct aatgagatct 169740 Page 115 715825 ‐ Sequence g.txt ttctgactgg aaattctgcc ctttttttcc tccataactg tattaccagt tatctctcat 169800 ccatgtgttt gataaatcca tatgaatgtc tttttttgtt ttctaccaaa acctttataa 169860 caaaacaaaa gctt tgtcaactac acttgaaaat tatgccccag gcttttcagg 169920 attctgtaat taacttattg agtcatttgt ttaaccattg gtgaattcat ttatctttac 169980 tcgggccaca gtaatgtatt acaa catattatga gaaactacat cacctgcttc 170040 accgaaattg aaaaacatta gatgaacaac actgccctaa accatatttc aataatcctt 170100 tcatgaaagg aaaggaagta catttcctat aatgatttgt tcttagtgaa gccatgttga 170160 ctccaagtga cctgttgttt cctttctggg ctcatagaaa taatctaacc aaat 170220 attgatgggg gtca aaggtatagt tttaaaaatt caccatattt aacctgttaa 170280 acattcagta tctcctacct tctgtcttcc ccaa agaaataacc atttattgtt 170340 ccgtttatgc tttcagtgtc taggacatag ctaatctgat actgaacatt tgaacttatc 170400 gttagctttg aaaatatgcc ctattgtcct attggcttta tactaaagtt ttattaatac 170460 attccctcaa tagtctccag tctttgccca agaagaagaa aattctgtaa gagtttcttt 170520 ttaccttcct ttcttctctg agtggaataa tcttttttgt tgtcttcata gtattttaga 170580 gttttgtgag atcagacaaa ctca gcttataact ttatctttta aaaa 170640 ctctgaacta attg tgtcatcttg aaaaaatagt ctatggaata tatataagta 170700 ttat ttttttcagt ttga cctttttctt catt gtgaatattt 170760 aaaaggtcat ttgtgcaaca tataagagga ttgacaggtt tccatgcatg atgcttaatg 170820 tggagatgat ttctttccat caagttatta tgcttggaat aagtaacaca tcttaaaatt 170880 acaaccttga tgtagcaaat catcagatgg gttaccatta catggaaaga gaaa 170940 taaagaccat taagttcagg tagacagaga tggcggtgag aaattcacag ccaaagaggg 171000 ccatatggag gtgaaaacac tggtaaatgg gacc ctaggagtct acagtaagtc 171060 attgggaagt tggagtggag aaaggcaaca ttagctaggt atttcattca ttcctccata 171120 aatgcttatt gggagcatgt tgtgtgcctg gcatcatcct agcttcactg aaaagaatga 171180 ggaacatata aaatgtgaag gtgagaataa gtgagaagta attgctcttt actctcaatt 171240 atagctgggc aagtacatat atgaatatgc ttttgtgttc caca ctaagcagtt 171300 Page 116 715825 ‐ Sequence Listing.txt ggtcaaagta ttaagctaga gacaacttct actttcaaat gtagtgtttc aaaataataa 171360 taataataaa agga cagtttacat ataaccattt agagatttaa aaat 171420 caggagggaa ggagaaatgt ctctgctggg gaaatttttt taaactagtg actc 171480 agctactcaa tgtgatttct tttattttct tccttccatt gcttattggc atttattgtg 171540 gggaagactg ctgtgttggc agcatgagag agatgggaat caagaaaatg gaaacaccat 171600 tcaatattca aaagccacta tccccttaaa caca gatcattcag ttttgccaca 171660 tactcagatt taac tggaggatgt taaaaagtgt tctattacaa ccagttatcc 171720 agtttttgcc actc tgctgtgaga aatgtgactg agcc ttaaaaagag 171780 atcatcttga tattaagcag tgttactcat ttgt tgacattcta acaggtgact 171840 ttgaatggat cttcaggctc agaaacatgg ttgtgtccct agaactggtg aggctggaac 171900 aaggtgtaca gaagtgaaat gaccacttgc tttctctatt cttt atccagctgt 171960 gcaattgttt cagggactac agttgatttt cctgatgcaa gcctagcaac ttgtttttca 172020 gttcagcaca gtaaaatatg aacaggagag aactccctgt ccca cctcacaatc 172080 tttaaaaggg aactctgtac agaagcattc tgcattaggc acac ttctgcaatc 172140 aaaatgaaaa acacttgagc tgaatcgttt ttcgttagct ttagtttcca gccctgatta 172200 aaaagaacac agggaaccct gcaagtttaa gcggttttgg cagccgagga aacagctgtg 172260 acattgtcaa gggttgtctg ctgt gcaggctgct actg ataatgccca 172320 gaaatggggc agacgctttt cgcatttggt catcaaagga gtggcagcag ctaggttcaa 172380 gaagtgaact tttgaccctg tctgagacaa ctggctctcg tggatcttgt tctgtcattc 172440 tccagtctga ttttctcttt cagaacaagt gggtaggatc tttggttttt aaactgtttg 172500 actgttatta aaagtaagct agttcttata gctgcgattg gaagggatgg aaggtgagga 172560 agaagagctg gtatttccca ctatcctgca ggggtgggga aatctatcaa cgactgttcc 172620 actaatctgc ggatgagtta tctagggaat atcatgcagt tgccaaagtt ttcagcatct 172680 aaaagcctcc ctct ctgtgagggt ctacctcccc tgtctccaga tccttcccat 172740 gcccctcaga actt gtccactgtc cttgctacca gggaatccct ctgcagcccc 172800 cttaccctcc tgcccctccc aaaagagctc cagactttga cctttctctt ccacctcaac 172860 Page 117 715825 ‐ Sequence Listing.txt atctgtttgt gtcttaaact gatgtccatt gaaagaaaca gataaactaa ttaatgctga 172920 gatatgactt tatt atgaatgtgc taactctctc aggggtatgt gcattttaat 172980 agaggaccag cagtccaaag gccggtctca ctccactgtg cccctctaac gagt 173040 ctatttccag gcagccagag accaggcctg agaacttgcc ccagaccacc agcgtcccca 173100 ctgagaaagc aagcagactc aacagttttt cagtgtttca gggagcctgc agcagcaata 173160 cagttccttc aaagggtctg tggattctct cagctttcct agtaggttgc tgtggtagtt 173220 tttggagcaa aagttcacga tctt cacatgctgc tctttgtgcc gagcaggtgc 173280 gcta gttctgcccc tatctgccat cttaatccta acatctccca ttta 173340 cttc tattttggtt tcagaggtac atgtgcaggt ctgttatata ttgg 173400 atgccatggg agtttggggc gatt tcatcaccca ggtaataaac atggtttcca 173460 ataggttagt ttttatgtcc tcacccgcct cccatcctcc acccccaagt gggtgccagt 173520 gtctattatt cccttatttg tgtttatgtg tactcagtgt ttagctccca cttataaatg 173580 agaacacgca agtt ttctgttcct gtattagttt gctcaggata atggcttcca 173640 tcca tgtggctgca atga gctcattttt tatggctgca tagtattcca 173700 tggtgtatat gtatcacatt ttctttatcc agtctactgt caatgggcat ttaggtttat 173760 cctgtgtctt tgttattgtg aatagagcct cagtgaacat acgtgtgtgt gtgtctttat 173820 ggtagagcag tttatattcc ttggattgtt gggtaaaata gcagttctat tttaagttat 173880 aatc ttcatcctgc tttccatagt ggctgaacta atttacattc gcaa 173940 tataaatatt cctttttctc cttg ccagcatctg ttattttttt gagtttttaa 174000 taatagccat tctgactggt gtgagatggt attcattgtg gttttgattt gcatttctct 174060 agtgaatagt gatcgtgagt attttttcat atgcttattt tccatgtgta tgacttcttt 174120 tgaaaagtat ctgttcaggg ttcc tatgaaaatg ctagttaatt atacaagtat 174180 tacttgtttc caataatcga ttttttaaaa aaccttataa tcaatattgc attaaaattt 174240 tcagctgtgt gattccttat cattttcttg gatgcaaatg ccttgtgtca cgtactatat 174300 ctcataaatc tatattgcat ctaacaaagt gctttgtgta aagtaggcaa ttaataaatg 174360 cttgtttaat gagtagattt gtttttgttt tattttgctt tctatgtttt cctaaggatg 174420 Page 118 715825 ‐ Sequence Listing.txt tggggcatta tgga aactgtctct caaaagttct tatatataaa tattgatgtc 174480 acta tttttgtaca aataaacaca taat ttggtgagca tttatagagt 174540 cctgcctata ttcaaggtcc ctgtgctgat cagtgggcaa ctgaagaagt atgaggcact 174600 gttactgctg tcttccttcc ctaattgggt cctatacctt atcttggtac agctacctcc 174660 ggcc catctgtgct gttgagggta aagg cagtgcactg gaatgtatag 174720 cctaggactg gaatttggag tgaggccctg agagatcata cacatttttc acttgtgggg 174780 gaatgtcctt aagtagaaat agatggtgat ttcagatatt tgatccaaac ctaacttcct 174840 catttgaatt gagtatgcta ataactattc ctct ggaatagtga tgacatttcc 174900 tggttgggaa atcagatgct gatttctgaa gcagagtttt aaagttgaaa gatgaaaagg 174960 gaacaaaaca ataaacacaa ccttagactg catt tttctagtcc aacttccctc 175020 gctg aaga ttgtccctca gccatcctta gaatattaaa ccat 175080 tgcagtgctc aaatgacttg tttctatttg cttg ccattggaga atttttctat 175140 atatcttacc ttaatggctc tccacgaatt ttgtcaacag tttgtcagca atgtactcat 175200 gaaaatatct tatg tatattctat cactttagcc tccttgactt ctagaccagc 175260 agttcccaaa cttttcaaat gtgacccctt ttagtatcaa cttctgttta taaaagtaca 175320 aaagccctca catcttatac tttcttttat gcttttattt attgagatat tagacaacac 175380 atacttgtag gtgacatgga ttcttagatc taaataactc cactctccat ggtcactgtc 175440 acttcaacac aggttgatgc agtccttagt ttggaaaaca gttttggcat aaataatccc 175500 aaaccttcct atcacttctt ggagcttttt tcttcatgct ttccttgcat ctttcttaaa 175560 atgtgaagac tacattggat atattattaa aataatgtca ttattagtgc tatgtttaaa 175620 gctgaccttt tcttcctagc cactgatata gcagtgccaa ctgtggactc gaat 175680 gaacacttta gtaataataa gtccttagaa cacaaacact gtcacttgta aaacactttt 175740 ctatacttgg taacctacac agaacagcgg ttcccagact ttttcttttt tttgtcttgt 175800 gggtccttta tatattctta caaattatta ccaa agagcttttg tttatgtgag 175860 gttttgttat tgatacttac tgtcttagta attaaaacta agaaaattgt aaaacaacac 175920 atcccattag ctgtcagagc atcatcatgt cttgtaggct ctggaaaact ccactgtaca 175980 Page 119 715825 ‐ Sequence Listing.txt ctcatgaaga atgagtgtga aagagccaaa tagtagctta atattattat aataatagtt 176040 taactttgtg agctcaccaa tataatacat gaca cagtccctaa catctaaaaa 176100 cttacaatct aaggcccaac ataaatacta atagatgatg ctaaattctg cagt 176160 gcttcctaca ataatactaa aaatatatga atttagacag aggccaaaat gtgtttatta 176220 tggc tttgcttagt attttgttac ccaccttgga gaattgcctc tgctgattta 176280 cactttataa gaagcagccc tatgaaattt tttatcataa gtttaacaat gatgtagaac 176340 atactgtttc attttataat gatccttggg caaaatgtat aatatctgtg ggagaaatgc 176400 tcaatgctgc aact ctcc tcagaatcag gtatgttctt atatggtcag 176460 tataaatctt ataactgtgc tttctgatct cctttggcca ccaggaagac aggagctgac 176520 aatccaactt actataaatt cttcagggtc tgatgtcatt atttctataa gattttccct 176580 ggcattatct tatttctcag gtctcacttt gttc tgatttattt ttcttaatat 176640 gttttattgt gtatttgtta atatgttttg ttgtgtattt aattgccaat ggggatgaat 176700 gaataagtga aaga tacttgatcc atttgagtgg gactgcttga gtacctggag 176760 tggtgcagac caagcagggt aactgtatca ggtttcatta atgaaatggg tcttaagtgg 176820 agattaggaa ggaaaggaag tgggttgctg gagaggcggg gtgttttatg tgacagattg 176880 ataa agatgcagct gtggagtgag tgagtgatgt cctgagcaca gtaaggagat 176940 ctggctgacg tggcactgca cctcattgcc ttaatatctt ttcatttgat tgaagaggca 177000 ggat tctt ggaaagtgga gtaaccattt ccaattaagg aaggactctc 177060 acttcagttt ctaaaataaa ttagaaggga gaaaatatga agtctgagag atcaattagg 177120 agaaagttct ggtgctacat atagaaatag ccgc atatgcaggt gagagtacga 177180 agaagaatct gtgaatggca gtcatttttt gtagctggtt ccaattaaaa ttgattctct 177240 ataatgacta cttattggct gctgctcacc aggtctgcct ttttcatcat tgtctgcaga 177300 acatatcaca gtatacagca tagagtaggt gcttcataat gtgttaaatg atgg 177360 gttcctacct ccaaaggaga tggaaaaaaa aaaacaggca agtaaataaa gtaaaatatg 177420 ttgc tttaagaatg ttttataaaa aaggacagta gcccaacagc agta 177480 ggctggctgg agtagcagtc attgaagaaa cccatgaaaa cagcggcaga agcaaatgtg 177540 Page 120 715825 ‐ Sequence Listing.txt cagctgctct gccttttcac actgtagggc agcacacgaa tagtcctgga gcaccagggc 177600 ccttagactg tgggattttt aagttaccta gttggcacag cattgactcc tcctctggtg 177660 tgattagggg ccaggataca ataaacatat gttatgttgg aactttgatg ccagcctaaa 177720 cttgccagtt cagtgtttgt ggttgcaggt agtatcagct cctctcctga tatgattgag 177780 agactgaggt ccaaggcttc aggttgaaca gaattgatgg ggat tgggttagaa 177840 caaa gcacttagca ggaagccagt ttacttttct tggatgccag cttccaagaa 177900 aagatcagtc ttgagcaaaa tagtccttca ctctcagctc agaagcctaa ttgagagggt 177960 atcctataag taacacagcc cactctgcta gtaacctgtt ctacttcaac ctgtaaggcc 178020 catgaggcta gaca tcactacagg acacagtgga ggatgtttag gaatggctgg 178080 acca gggtgcagat tgtgtttact caaggctgat tgagaaatac tgttttcagt 178140 ggtgtgctta taaatgttta acagtggtgg gggg ggctctggct tgtagcattt 178200 tgcc catggtgtaa atactcccaa catgaccaac tttaagttac caatgtgatt 178260 gaaagtagag agcg agta gcccactgtt atgtagtatt tttgccatac 178320 agatgcataa gagacataag taacctgaag aacatagata attattaaat gtagtaaaat 178380 gatcatgaag atct tgagtgtttt atcacatttg tttttaatat aatttaattt 178440 taagttgcca taatttaatt tgtaattaag actatgttaa taattggctt atggaatttc 178500 tgagaattca aaaaccagtg cccataggtg gatccagtac accactaggt aagaacagcc 178560 tact tctaggctct tgttctgaaa ggtgccaaga ctggcatcca tggttccagt 178620 gccagggtcg aggaaagact tactaggtcc tgcagtattg ctcccaaatc agtg 178680 gccagggaaa ttatcagcct gaaggcaggc tgaatggctt attc aggtcccagt 178740 atctacgatt gacaatcggc ttcatttgta agtaccagat agtgcaactc catgtatcca 178800 ggaggctggg aggtactgag agcagactga tagtgtcaag agacactgaa atgactgcca 178860 gctctctcct gccatatcca ctactaagtg agaaattcag tgacatagtc actgaggact 178920 ccaccactgc tgggtgttgg ggagggcaca attt caagacaatc agat 178980 ttttcttgga gggattcaag tacaaaatag ttaatatgca aagc agaaattatt 179040 atacctcaga aatgagtcag ataatactaa agaaaggaag aaaggaaagc atgacttgat 179100 Page 121 715825 ‐ Sequence Listing.txt tcatgtcttt aatgatgacc aaagaagttg ggtctttaaa gatgacaaga gaagactgat 179160 caggtagcag tgaggtggaa ggggaaagat gagagagggg acattcctgg tagaggaagc 179220 aaggtagaca aagtgtagga atgtgaaaga gcataatgta tgtaagtatt gttcaggtga 179280 cttcttgggt acctagatag tagagagaaa ttagaggtaa gaatggagga aggggagact 179340 cagggccagg ttgttgaggg cattttatgc catgctaagg agtttccaat ttttcctttc 179400 agtaatagca agaaacttaa aatgagcagg ggtttgtgtt tttgaaagaa ctgggaaaac 179460 acctctgggc aatccattac ctggggataa tgggtgaaat ttcccaagtt cagg 179520 ctgctgggta gggcttgagg ctttcctctt tatt tcaacactgt ggtcttttag 179580 gacttgtcct caacatgttc ttaaaaggaa ctaa aaac agtagtcttc 179640 atatttattc tgttcctttc caaaaggtaa attgaaaaag caacataccc aaga 179700 gaattaatct tttatcacct aagttactgc cctt tcagttttaa ttta 179760 gtgtgcataa atggctatga gcccctggaa ctctctttat gtttgcatct taaatttacc 179820 agaccctcct tctgcctcta gttccagaat tttctttgtc ttattttctt caagaaatgt 179880 ttaa attggattgc aaatttggaa tacacacagt cttt taaaaccatt 179940 cttttaaaaa aggacaagtt tcttgagaac atttttaaag gaaaaagtta aaatagatgt 180000 caatggaaga tgcaaatatg aatataaaat atgaaaagca ggct ggagcttctc 180060 agtagagctc tacttcattt atat tatctggcac aaag cttttggtta 180120 cttgattttg tagttagaaa aaaagtataa agttgaaata ttgggctctt tacatgacca 180180 ttttgctagt agcagtggat gaagcttttc tctaagagat caatagcttt agtgtaaact 180240 tggtcaatac cttattggaa gaggtgacta tgtcagatta ggtagaaact ttaaaagcca 180300 gcaagtttcc cctt ctggaattgg cctcctaggg ccatgtggac cagagagatc 180360 ttatcacaga agtcataaac tgatatccgt gagccaaatc tagctcatgg gcatgttgtt 180420 tggcctacag cacatttttt tttttttttt ttttttttga gacagagttc actctgtcac 180480 ccaggccgga gtgcagtggc acaatctcag ctcactcaac ctctgcctcc cgggttcaag 180540 caattccctg gctcagcctc ctgagtagct gggattacag gtgcccacca ccacacctgg 180600 ctaatttttg tatttttagt agagatgggg catc ttggccaggc tggtcttgaa 180660 Page 122 715825 ‐ Sequence Listing.txt ctcctgacct ccac ccccccgcct cttggcctcc caaagtgctg ggattacagg 180720 cgtgagccac cacgcctggc ccacaccaca tttgtaagca gatgaattgg ttatttttaa 180780 aaatttgaag aatttaacaa caaaaacaac aacaacaaca acaaactttt gtgtccagct 180840 tctttttttt tattgtccca atagttaagg acaatcctgg gcctgcattc tttgaacagt 180900 tggctagact taagtagctg ctgccccttt tagatggggc tctc tactttttca 180960 cagtcccctt caagggtgct tcagccattt ttgctactca cttgtcttca ataaaccaag 181020 gtcatgttta aaagattaaa taacagttat tgcatgctca ccaaaccgtc acaaggaacc 181080 agacttgtgt accagaacag ggag catatctctg ttaggctaga catcactctt 181140 ttagttatgg gatcatggaa aggtgcagaa agttccaggg aaggggtcgg tttg 181200 gtgagtgagg cacttggagg tcaa tagcttttca agca tggaagtact 181260 gttt aaaaacctat ggcacagtgg gatcttctag gaaagtagac cctggagatg 181320 gagattcaca tgtagcacat ttattagggg ctag gatcaatatc tgtaaaagag 181380 agagaaagga tgtaagagtg ggcagaggga gaagttgagc tgcaaagcag gcccagtgcc 181440 agcctcaact ggctccataa ggagctctgg aatg cccttttata tttgtttccc 181500 atgggaccag gatggctagg ccattctact ctgacatgca tcactcactg aaagtgggaa 181560 gagtcttgct cttgagtgag ccct gagg caatccctca aaggagtaag 181620 aagtgaaagc tcctggcctg gagcacctgc aacatctgaa acaagaaatc cttcattgaa 181680 caggatctgg gcagcacacc agagtgatca cagtcagcag ctataccagt gacaacagat 181740 gaatatcaac tctgccttta gcccctaggg tatgacacct ggcctaccaa ggctgtgcct 181800 aaactctttg ttca gaatcaagca agtcctagcc taaagagagg agtttaatgt 181860 catgctacgc tctagcccaa tatttgctga cttgtaattc agtcattaaa aaaattcttt 181920 ttatcttcac atagttttag aaac tgttaccgtt ctgtgtccag aaattaaaat 181980 ctattctttc tattcttttt tttttttttt tttttttttt gtgacggagt tttgctcttg 182040 aggc tggagtgcga tggtgcaatc ttgtctcact gcaacctccg cctcctgggt 182100 tcaagcaatt ctcctgtctc ctga gtagctggga ttacaggcgc atgccaccat 182160 gctcagctaa tttttgtgtt tttagtagag atgaggtttc atcatattgg tcaggcttgt 182220 Page 123 715825 ‐ Sequence Listing.txt cttgaattcc cgacttgagg tgatccgccc cgctcagcct cccaaagtgc tgggattaca 182280 agtgaaatct attcttatat tttattgtaa cctcagaaaa gaatgctttt ttgaggacta 182340 tgtc tcttttattg tcttctcctt tctctttccc aaacctataa ctctattttg 182400 cttagcacac aatgaataat cagatgtctt aaattgtggc ttacataatt actagtataa 182460 cttttttgct tttttttatt tcattttaat ctgttcatga ggactgttac ccaggtattt 182520 aaaaaatctc ttgt tttaaggtta ccaa ttta gagaccctga 182580 cccaataata gttatatttt tctaagtggt tctgaagcaa tggtcacaag taagaaactg 182640 cagttcaaaa cacatcatag gtttgttatt attc ttattaaagc attaatgcaa 182700 atggaatttt cctactagta ttctgctttc cctt gacaggacta attgctaaac 182760 tataatatga tttattataa ttttatgttt atattaaaaa tatagaatat gattgccctt 182820 tgatgtcaaa tactaaagat cctgctacta ttttagttgt gctggttctt ttcttcctta 182880 tctttcattc accttttcaa tcat aaacatttaa tgaaaaactt attgtgtatc 182940 aagggttgtt tattatatga tttgtaattc aaaaactttc tggt attt 183000 tagaaacatg aaaagaaaga gggagggaga ccaactgaga gtataaaaat aaatctggca 183060 tttattaaca gttaaccaat ttcttttttc tataataatt tatctactaa actgtatttt 183120 ttaaattatt gttttagttt ttgttgcata tatttaaggt atacaacatg atgtttttta 183180 taattactag agtgaaacaa attaacaaac ccta catagttatc ttttgcgtgt 183240 atgtgtgtgg taagagctcc agaaatctac tctattaaca aatttccaat atgcaataca 183300 atattattaa tgatagtctt tctgctgtac gtcagattcc tagacttatt catccttcat 183360 aactgctact ttgtaccatt tgaactacgt tttcacatcc cctgtgaaaa tgggaggggg 183420 gccgtaccat ttgcatggaa tatctttttc catcacttac cttttactgt atgtatgtac 183480 tcagatctaa actgagtttc ttgtggaaac catacagttg catt ctttacccat 183540 tcagccattc tgtatctttt ttattgagga gtttagacca tttacaattt aagtaattat 183600 tgatagggac agatttaagc ttgccatttt tgtt ttctatttgt ttataattct 183660 tctt gctctcttct tttt gttggatttt tatgctgata ggttttgatt 183720 tcttcttttg tgtaacttct atatattttt tctttgttgt caccaaaggg cttacataaa 183780 Page 124 715825 ‐ Sequence Listing.txt atattttaga gttgtaactg tccaatttat gctgatagca acttagcttc ctttgcttat 183840 aagaactctc tgcttttacc tcttctcccc cattatatgc tactaatatc ccaatgtaca 183900 tctgtttata ttgtgtatgt agtaacataa tttagttata gttgttttaa tacttgtctt 183960 ttagttttta tagtagaatg aacatattta cctaccactg ttatagtaat acagtattct 184020 gtattatttt ttaccaatgt gttccctact cttt gttt caattttaag 184080 agctatcttt ggcatttctt ataaggcaaa tctagataaa ctctctcaac ttttgtttgt 184140 ctgagaaatt atttatcttg cctttatttt tgaaggacag gattgctggg tatagccgtc 184200 tttgttgtta ggttttgtgt tttttttttc ttttttcagc acttggaata tcaa 184260 ctcccttcag gcctgcaagg tttctgcaga aaaatcgtct gataatacta cagagatttc 184320 attataagta gcaagtcact tctctcttgc tgctttcaaa attctctttg tcttcaactt 184380 ttaacaatta taatgtgtcc tggcgtgggt ctctttggat tcatcttact tggtgtcgtt 184440 tgggcttcct ggatctggat gtttattttc ttcccgggac tggaaaatat tcaaccatta 184500 tttctttgaa tttttttctc tctctcttct ccttttgtat attccgtaat atgtatatgg 184560 ttga tgttattcca aaattccctt aagctatctt tacttctctt cattcttttt 184620 tctttttgct tctctgactg gataatcatc aataatctgt gtta gctgatcttt 184680 tcttctgttt gtct tctcttgaat accttctgag taaaaacaaa caaacaaact 184740 gtttttcctc tgctttcaca cagc aatcagtaaa cttt gtgacaaaat 184800 gtgtgtttag ggaaggggtg gtttccttca cacaacaagt tcag agta 184860 aataccagtt tggtgtcctc taattcaatt cttc tactgagaga tcctacagat 184920 tgggggctca gtccccgaga ctgtcttcct caaccaactt ccaatgccaa ttgcaaaccc 184980 caggttattt tgcctgtact tcttactgac tggctataaa ctgaggttcc cacaaccccc 185040 ttctgaggtt caattaattt gcaagagtgg ctcatggaac ttggaaacac ttgcttatgt 185100 ttatgagttt attataaagg atattttaag ggatacaaac ccag aagaagagat 185160 ggta aggtcaggaa gggtcatgag tacaggagct tctgtccttg tggagttggg 185220 gtacacaacc cttcggacat gtagatgagt tcac cttcctgtaa gccttcacat 185280 gtatagctgt ctagaagctc tctaaatcct gtactctttg gccatttatg gagacctcat 185340 Page 125 715825 ‐ Sequence Listing.txt tggataggca tgattgacaa ggaa atgtgattgg agag tattagctag 185400 tgctaacaga ctgaatggaa aacccagaaa ggcctgtctg ttcagattct tcctggtctc 185460 cagc attctttcct ccagggaatg gggcaggacc ttttttgaaa tgaaaatctt 185520 taca atcagacaaa gtaggtcaga gaatttcttt atggccagag gcaggggaag 185580 gtgt atttttagtt tctgttgcct gccttatgga gaaaaaggaa caggtgaata 185640 gagggtaaga cata gagagatttc tgttttttga ggcctgcttc taatgtctaa 185700 agcaccccag cattataata aaagactgta ataagagcta aggaagttat gagccaggaa 185760 ctgtggacaa agtaatatca cacccctcta tttttttttt ttttttagtt tacttactgt 185820 attatttatt tccatgattt ctgtttggta ctttttaata ttttctatct ttttgttgaa 185880 atctcacttt gttcatgcat tgctcacata aactcagtga gcatctttat ggctgttatt 185940 tttaattctc tgtgaaatca gttacctcca tttcattagg gtcagtttat agaggattta 186000 tctagttctt ttgtttgaaa tatattttcc tatttcttta ttttccttga agag 186060 ctttctttaa tgaa atagccatct ctcccagtct tgtcaaactg gctttgtgta 186120 gcagaggtac ctcaccaatc aacttgacca tgtg gtgcctcttt tttttttttt 186180 tttttttttt tgagacagag tttcactctt gttgcctagg ctggagtgca atggtgccat 186240 cacc ccaacctcca cgtcccgggt tcaagtgatt cccctgtccc ctgtctcagc 186300 ctcccgagta gctgggatta caggcatgca ccaacacgcc cggctaattt tttt 186360 ttagtagaga ttct ccatgttggt caggctggtg tccc gacctcaggt 186420 gatccgtctg cctcgacctc ccaaagtgct gggattatag atgagagcca ccgcgcccgg 186480 cctggggtgc ctcttaaact tttgtgctta ttcaaaccac cagttttgtt cttagtggcc 186540 ctcggtagga atgtcccaag tcctaagtta gtgaccaagg tagagaaacc tgtccctcaa 186600 gaagcagcta gaaatattgg ggctctagat gagtggtcca tcttcctctc tcctcaggga 186660 taagctggga cttt ataccccact cactctgcag tccagataga ggatctgtgc 186720 caaatgcttg tgctctattt cagacaatgc taaa catttacttt gctctctcaa 186780 atggcaggtc tcattagctg tcctggataa gtgaattagc tggaagcttg gttatgtttc 186840 tggagtgagg agctgcagga agtgccctca tgcctgttca gactcccgga gttctactaa 186900 Page 126 715825 ‐ Sequence Listing.txt ttgcctgctc catcagctcc cagg ctaattaata gcttaatcca cggacagcag 186960 ctaggaaagt cagaatatta tgtatgcagt ctaactccgt ccagggagaa actgagagct 187020 tttt gcttgctcac tcttcactga gcttggggaa ctagctgctg gtagtgcaca 187080 tgagctcatt taaaaccact tctttgttcc tctt gggggacaca taaatgccag 187140 tcccccatag ctcccagagc taggtgattt cagagccagt ctctcaggtg ggagctgtaa 187200 aagttggggt gctcaatgta tggacaaact agga gagattagat gcttgatttt 187260 atcattggat tgagctgggg gagaaggcac aggaagtgcc cacacactag tgcccacata 187320 catacccttt caagctccca gaggtcttac taattacctg ccccactggc tcttagtcca 187380 cttagtaatg ctataaggaa tacctgttgc attt atgaggaaga gaggtttatt 187440 tggttcatgg aggc tgtacaggaa gcatgatgct agcatctgct tccagtgagg 187500 gcttcaggct gtttccactc atggtagaag ggga gttggcatgt caca 187560 gaga tgaggcaaga aagaaagagg agaaggtgcc aggctctttt caacaatcgg 187620 ttctctcgta gaaactaaga ctgagaactt tgcc ctgacaaggg caccaagcca 187680 taaatgagag ctta tgacccagac acctcccaca aggtccacct cccacactgg 187740 ggatcaaatt tcaacatgaa gctttctggg gccaaacaaa ctgcatcaaa ctcc 187800 cagttttaga ctatgtagaa ctttaatcct tgggcagcag ctgggaaagt gcaataaaac 187860 ccctaccaga gagaaactag gagttgggca atatcgcctg ttcactctgt actaagcctg 187920 agggaattgg ggtaggaagt tcttgcacac ctgtttaaaa ttgccacctt gttctctgtg 187980 gtccagagat aattgcaaat gctgagccta tctgcttcca gagctaggtg aattggtgat 188040 tatggtttgg ctctgtgtcc ccacccaaag attgatcatg gggacggttt cttccaagca 188100 ttctcatgat tgag ctctcacaag agctgatgaa gttttaaagg gcag 188160 ttcccccttt tttc cctctctcct gccaccatgt aagatttgcc ttgcttcccc 188220 ttcaccttcc accatgatta taagtttcct gagccctccc cagccatgtg gaactgtgag 188280 tcaattaaac ctctttcctt tttaagttac ccagtctcag gtagtttctt tctagcaggg 188340 tgaaaacaga ataatataag gagcaagtcc ctcagggagg agctgtaaaa gttgaggtgc 188400 tatatgtgtg gtcccaaccc tttaacttct aagaaggtaa agctaggagt tgggtttcct 188460 Page 127 715825 ‐ ce Listing.txt tcctgattac aaagtgatgt gcctgggtgg tgctattggt gtgaattaac caatttctta 188520 aacatcaact tcca aactgtgcta agggctaggg aaaaggcttt gttatcctta 188580 ttctgagaga gcttatagtc tgattaggaa aact gacacaaaat aacagcaaat 188640 aacaaggcaa cataatcagt tgctacatgt tatggtggta tataaatgat ggtagaattt 188700 agaaaactga aaggggacag gatagacaag cagg gcat ggaagagaag 188760 gaacttgatt tgggatagaa gaaggggctg ggatttggga agacaaaaca gagg 188820 gccattccag tatccaagta atgacagata gaggcacagg gcatgtatta acacgagaat 188880 agtt tgatgttggt tagaacttac taccaacttc ttacagaact ttcctctaag 188940 aattatgagt ttgaaaacat tcaacacctc cttt caagatttcc tggcaaagtg 189000 aaggaagcaa atacctttat tattttacaa ctgaagttac ctgttttgtc agttatgatc 189060 taggctgatt acct atgggcaacc agtc aaaagagcta ggaattcatt 189120 caaaagacca aaatctgcat tgtctggtag tgtgagcatg agcaaatcac ttcatctcct 189180 tgagccccag ttttctcatc taggaatgaa aagtagagcc ttatctatct gaccaggtta 189240 ttatgctatt aagttatata agtaaatgtg aaaattcttc ttaaacaata aaacaatata 189300 aattttagtt ggtacttttg ttaacatcta cactagacca cgtttatata ggtaatttaa 189360 aaataaaaaa gaatggggaa ttcattctta tgtcatggat ttatattttt tttgtagtac 189420 aaagttaatc gctcagcagt gtttgttaca tttcaagtag caaccatcat attgccatga 189480 aatttattta gtaaccccta actacttttt ttttaatgaa atagcataga atgaaagtat 189540 agtgtatatt gtacttttta gggcagtaga ttatatcatt tgtcataaag atgagtgtcg 189600 tttagtgaca cacaaaggca acat acacactggt gtaa aatatatttc 189660 tttttgtgga ttgttgtcaa agaagattga ctaa ttaataatat agtatttcaa 189720 aatc ctcagtcttc atattttgaa ccctcaaatt aaactaacca aaaagataaa 189780 tttcagagaa aagttatttt atgtaaagaa agtgagattt tgatgaaatg agacatgcta 189840 ccacatattc ttct tcttatgtct cttgctgaaa cccaaattct gtcttcactt 189900 ctgctgccca agtatacaaa gcaaagggat tttttgtgtg tgtttccatc aaaagctaca 189960 tgcctagaaa ctcattgtac tctatttttt ctggtagctc ttgagttgtt tattttaact 190020 Page 128 715825 ‐ Sequence g.txt atcaatcaat attatataat ttaaaaataa aaacttaatt tgtgacaaag taagttttca 190080 gtctgggttc gaaa gggatggcat aaat gatgtaacca ggaagaatgc 190140 aataatatgt ctatgtacaa gaggggtgat agaattaagg aaaccaacca aagatggtga 190200 agaacccaga gctaagaaaa gggtactagc tcccaggcct gaaaggtcac agtgttctag 190260 gttccagaag tgag cagtgggaga ggagcaatat tactagtgcc atcatgggaa 190320 accagtcttt tcaggaaaga gagaggcatg gaggggacag gtgccaatgg ctgaacccaa 190380 tgaagaccaa gggttctggg caatgtcatc tgtaatggcc aacttcctgg ggcacagagc 190440 agggaagacg agagtggaaa atgagtgtgg agcaacaaat ggggagtaac ccta 190500 gaat gatcattttt catgtcagat ggtggcatat agcttttcta ctcaaattca 190560 gtttccttcc tgct aactggccta gaccaatcct gatctagccc atggtagttt 190620 actttggttc gttg ggtagccaac cagtggtgtc ttcctgcagg aacttcttag 190680 aagggccaaa gataaaggat tcct cattgatttc atagacacaa ccagttctag 190740 atcactggtt caaagagggt aataaattag taaagtggga gaaa ttaggaagat 190800 tcatttctgc tttattgtga actgggtcaa tttttgcttt cttaatatta atcttgaaaa 190860 agatatcctt tgaaatctca aaatcctttt ctgtaattta aaaacaacct taccatctgt 190920 gtcctctgtc atatggtaca atattcaaga gggtgaaata atggtccagt gactaagaaa 190980 aaccttaaag gataaattgg ccttagtgac tgtcactaaa atgtaaacat ggctttaaaa 191040 agtaaatcag gaggcatgaa agggccttga cagctaaggc tctcaggaag gaaa 191100 gacatgaagc acaattttat aagtgtgata taggagttac tcttcttttt ttattcatgt 191160 gtcatagaag ggaaaggaaa tttctaaagg agtaagacca gccagatatc acaagaatat 191220 acaggaatgt aaggatagca tgttcaaggg caacatgagg agtcaaagaa ctgg 191280 atgccaagac tagctgtgtt gctg ctggctcctc cttggcaaac acaccattgg 191340 caatgaactg atctgatgtg tcta agtccttgag actctctttt tattgcaaag 191400 cttgccagcc tctttaccca gtacatgtac tccactctaa gaagaaaaaa caaaactaag 191460 tgactgctaa gctcatggac aatgtttttg ggtctctcca gcagccagct agtggctgac 191520 taggtaaaat catttatttt tctcaagatg ttgtgattct gggaatgcag ggtttggctg 191580 Page 129 715825 ‐ Sequence Listing.txt ccatgttagc ctggattttc tgagatgcat ccctgcaaga gattcactgg gaaattagat 191640 gtgcaagaga tttatctggg gaaatgccta tgagggaaaa tggagaagga gctgcagaag 191700 gctggaagag atgaccactg cagtacaggt ctaatcccag tggaaaaaaa aaaaggagag 191760 aaggaatgag aaaagggaaa gagagaagga gggaagaaag gaaagaggta gggagggagg 191820 gaaagtctta gacatcagtg cagtgccaag aaagttttgg caaggctgat ggggagtctt 191880 caaaccaaag tcacttgaaa gaggaatccc ctcatcatcc ctctaggaat gggcctgcct 191940 tggtgtcctt gtcatgcaaa gtcactggct gggtggattt atag cagctgaggg 192000 cataggccag ttacactctg ccataggagg cttgagagat gcattttcat agctgccaca 192060 tttgccactg aaaccttctg ggagtgatgg gttgtgctgg aagaatttga agatactatc 192120 ttatgctcca gataaagaaa tgcattgatg aaggcccttc agat ttatttttgt 192180 gtgtcccaac tattatataa attcccctat caaggaattt tcagtgtttt ctccttgccc 192240 atgt gatcttatat cccaggtttg ctgagacatt cctcttacag atagttctac 192300 tggctcatga gtgtaatgtg tctaaatgta tggttggaaa aatgtggtta ttagatctaa 192360 attttaagtc caaatttcct tagcctgaag gtct tccacagtct agtcccaacc 192420 actttttcca accttaatta cact ttatcctgta tttcaattca tttgaaatat 192480 cttt ctaaattact cttgcttacc tatc tctttgttca tactgttctc 192540 ttcaactaag gttaattaat caacatgtat ttattgcccc cttcccatgg gccaagccct 192600 agaa ctgtatgtta ggggacaaaa cgcacatggt ttctgtcttc ttagagtttg 192660 aatttagtag aagaggaaca gacaaataca caggtcaatg gacagtgcat gcttacaaat 192720 acag tgtcaaaagt agag ggttccctga cagagaatta gaggaaggtt 192780 ttattttaga tatc aggaaagaaa tggcatttca actt gaatgataaa 192840 gggaatgtag ttactaagga tcct gcaggtacca gttccatcat cttcaagata 192900 ttgccatgat cttcacaaaa tctttactga ctcatcattg gactctcaac caattttagc 192960 cctgtgctat ctgcatcttt tatatcacag aaagtgttga tact atatactaaa 193020 tgtgtttgtc tccaatcaga ctataagatt gtggaatgtt agacccatgt gtgatgtatg 193080 cctttgtatc ctatcagatt atatgatttt ggaaggttag agctatgtct gtatccagca 193140 Page 130 715825 ‐ Sequence Listing.txt taatatttat ctctgtatct gcatgatact taggataata gtatgtggcc acatccaaca 193200 aatacttgtt gaatgaataa acagtattcc actctctgca aatttggtct ttctgacatt 193260 tgtctgaatt atagaaggag aaggaggctt tacataatag ttgaaaatta ctgttcatgt 193320 aatacagagt tctgaacttc aaccagaagc aagtctacag cagatgaaaa taat 193380 gagggaatta gctgtggata actttcggat aggatgttat aagtttagca ttaa 193440 ttat tatatgcata tttt aggaagaaaa tctggctgaa acaa 193500 ttactatttt gttc ttcagcagtt cact ggcttctaga ctgt 193560 tgtttttttt aatatatcaa actagcatgt gggttgagac acaacatcac attacaaatg 193620 ggtagtccct tcacttgtag cagt aataatatag atactgattt ttacagtttg 193680 taaaattatt gtcatttctt tctcttatta tctgtattct cagaaacaaa gagtataaac 193740 aaagagaaag ggcatgatgt atttttgata ggctaccatc tcaaattttc atttcaatgt 193800 ttatttggag aaacactttt atctaaaatg gaccttttcc attttacaat tgcacttgct 193860 atga gaactgcacc ttccaggaga gatttcaatc tgactccaaa gccttgaccc 193920 tcacaaacag tgttgtttgt aatggcccct ggttagaaac tctcagccta acaagcatgc 193980 agcatagccc ctgaagtctc tcctcctatc tgcataaatt ggggatgtag aactcctgca 194040 tatccagcct cacttactca taaaatgctg ggaatcattc caaattgctc ttccagagga 194100 gggtttgttt ttaaaattat ttcagataga gatgtttcaa attctacata aatgcataat 194160 attatttctg attgtgcttt cttggtattt ctcttcctgt aacacctact tagccattct 194220 ccagggacca cttcaaggac ttttgtaatc catatagctt tcctaagctg ttctaacttt 194280 cagcaatccc aaccacatca ctgaccgagt ttgtaatgac tcaccagaca atgtgttggg 194340 tcctctagta atactttgtt aattccaagt tatccttgct gctgttgttt ctccgtgtgt 194400 gtttctatct gcgctctcca gttaagctgt aatcaactta accactgggc ttat 194460 actctacttc tcacaaccct tgcctcttaa attggttaat gtatgtttga tgactaattg 194520 taat agctacttga ttct taagaaaggg acaaattaag tattttccct 194580 cctc tataccaggc atcgctgtgg aaagctgcac agttgggaaa gcgtcatttc 194640 aaaaacagga aaaatcacct tatt tcagggattt gactttgaca ttatgttgac 194700 Page 131 715825 ‐ Sequence Listing.txt ataaaagagg cttaagaaca gctattagaa aatagaaaca tgaa tgagtgaatg 194760 gcatacctaa atggcatgaa atgtgaaaat gatacaaaat gtaa tccttttttc 194820 ttctctaatt aatctccact gggtatgggg aatagggaac aactggggta ttcgtaacag 194880 gcaaacattc ctgattcttg ccctactaaa ggtagggaca ttaggagaaa ggatcatcta 194940 cttggaaaat aaactggcat tgctaagtct aaatgattga gtcaagtgca aattttatag 195000 gccaaataga attttcacaa gtccattgac tgttgaaaac tacttgtacc ctggctcaaa 195060 ggacattttc ttgctgtctg tagtaagcgg tctgtaaact gtgtttagga cctgaaccga 195120 atgctggcct ttcacttctc aaactatagc ttagtaatcc cagctcagaa gtccctccat 195180 acacaattta ttaa catcagagca taaccatgct ttgttccctc cagaagtaaa 195240 atgtgaagtt tcttcccatt ggaagtctat ttattattag tttcagatgt tgtgacaccg 195300 ttttcatcca aatgttagag aacagaaaga agcctttttt aaaagcgtaa ctttcattat 195360 tcatctaggt ttttttcagg gtccttgaga aatgctaaga ttatgccttg tgtttgagaa 195420 gtagaaaagg aaaaagggag gaaaaccacc agtg cttctcaaac tttaaggcac 195480 acatgaatca cctggggacc ttgcagattc tgattctgaa ggtcagaggt ggggcctgac 195540 atcctgcatt tctaacgagc ttccagggga tgctgatgct gctggcccac agaccatact 195600 acctagagca gcaagcttta taggccatag aggacatttt tttttttttt tttt 195660 ttttttttgc atggagcaca gattactgct tagg ttacaattcc aaggaaataa 195720 tgactaaaga aaaatactgc tgtttcaaca tttctgagtc atttagtaag aatggaaggt 195780 taacattagc aatttaacat ttcaaatgtg gtgggagtat ttattgatgt actaatttgc 195840 attttgttcc tgccaaatct ttttactctg ttggctccag ggagtttgaa agtctaggac 195900 agaatttttc ggtt tgtttacata aaaa gaagtgagca tctttggagt 195960 taaggagagt taagacccaa ggagaagaaa gaaaaagact atgaaagatt tttaaaatgt 196020 ttatccctgt gtaagatctc caaagcccct cccttgaccc agtagtagca gcca 196080 cagtgatggc tgaaattgaa tatcccacta acttggtaaa agttgggcag gctcccagtc 196140 agacttaaat cattttagag aagtacaata atgtggcatt accc tggtgatatg 196200 atac atacctgctt aaat atgg actgttaaca agaatgtacc 196260 Page 132 715825 ‐ Sequence Listing.txt cttaaagttt tgtaaactct acagcaaaga aaaaaaaaac tgctacagaa aaaataagga 196320 ttttttttct acca gcgacctata ctttcatttc ttcatgttac taattacaga 196380 aactttcagc agaaatgtat tggg catcagttag ttctaaacat tttagctctt 196440 aggagcctct atct gttctgttgt tagttttgct ccctgactag attgtaactt 196500 ctaagctcag tgtc tgcaactact tttctttagt cctaacctaa ccaagagcta 196560 ggcatttagg aaatgctcac tataaatgta ttgacaaatg attatgtata attagctctt 196620 aata tttttcatca tcaagaaata gatttaaagg agatattttc aaacagtatg 196680 gatgtatcat ccccttacct ttatgtatgt gtctggttgt gaatagtcag cacatattat 196740 ggttaaactc aagaaacaag ggaggttatt ttctaagcct gcatcatagc agtagaaatt 196800 tggaaaaaaa caaaaaacaa aaaaaaaaaa acatagaatt aattgagttg taatcaaaga 196860 aaattatgtg actataaatt gtaatatttc taaaatatac ccacatatgc caatctattg 196920 taagaaaatg ttcgcagagg gaaaacaatg gaaattccta gaagctttag atagattcta 196980 atgattggaa ataagtatta caaatggtcc acattttaat gtgacttcta gaatttttta 197040 atag tatcctttca cgctcttatg ctgcttgctt acaacataca tcac 197100 gtttttctgt taggaaatat catactaatg atttgtgatc atatttacca cttggggatc 197160 gcca tgataaggaa tttggacttt attctgatta catgggaagc cactagagaa 197220 ccag tgaggtagca tgatcttact tatgccttaa aaaggttaat tgttttggta 197280 tgaa ggaaggcaaa agtggaagta ctag ttaggaaact atttgattgt 197340 tcgggaaaaa ggtgctggat gcatgggcta taataatagc aaaggagatg gagagaagtg 197400 aatggattga gatggaactg aaagaacttg ttgatggtta aatgagttgg aaggagttag 197460 agaaagcaaa gtgacaaaga tgactcagaa gtgtttggct taagtacctg agtggatggt 197520 gaaacaattt tcagacatag agaagaattt aggaagaaca gtttttttca gctc 197580 gagagttctg tgttaggatt gagataccta ttagatacca actgaagata ctgaagaggc 197640 gagt ctgaagttca atggagaggc tcagactaag attt ggaaccatca 197700 atgtgtagat gatatttaaa gccatgagac tcgatgagat tccctttgca ggggaaaaaa 197760 aaaaaaaagc tagaatattg gagggaagag ttttgtaaca ggacaatatt tatgggtcgg 197820 Page 133 715825 ‐ Sequence Listing.txt gcagaggaaa agaagccagt aaaggagacc aagaaagaac agtcggtgag ctagaaggga 197880 caccaagtgg ctcaggcatc ctcaaagcta agcaaagagc atatttttaa aagacagtaa 197940 tgtactgggt caaatgcctc tgagaagtta agtaatataa gaaataagaa gggactattg 198000 aatttgatat gaacaggttt agtggaatgg aaggattaga agtaaaacca aagtagattc 198060 agaagaggag aaattaggaa gtagagacag agac ttaa aagatccagg 198120 aatggaaagg aaattcctgg gagcgcaacc cctaagaagc caaaaataga gtatgctttc 198180 catgtaggtt tttaattctt ttttggtggt gttctttaga aagagaaatg tctgttggga 198240 tttg aaatggtgtt ccaa ccatttctgg cttctataga tccccttttt 198300 gtacatgctc attcccttaa aaaaaaaaaa gaagaagaag actagatttt ctaatttagg 198360 gcaaggggct aatagcaaac caaactcatt tgtaatctaa acat attattttgg 198420 ttgctcttca gtggcactag ctgctgctag gaagttcatt ttacacacac acacacacac 198480 acacacacac acacacacac tttg ctgcagatcc taaacttgaa gccctggatc 198540 ttccttacat catttaccca gaagtatctt tgtcaacctt cttaacttac caga 198600 aagtagaaca aggcagaagt ggag ttctgttcct ccccatttcc cccctcacct 198660 gctggcgtca taaa tactgtgttc agaacttggc taactgcttc ttttcccaca 198720 cagg gaatacttaa agccatacag tgtccttgtt aaaa gcatatgggg 198780 caggttgccc cttcaggctg acacaaagac acactgtgca agacatctat ggccagtgga 198840 gtggccgtgt atgggttatc aatgagactt ttgacttttt tctttatgtc atattgtcat 198900 cacattaaat agaattcaaa caaggaaaca aaatttatat tctagacttt taaggcattg 198960 ctat agctatgaaa cttttctttt tcatacctgg tataattttc cactttaaac 199020 aatgttgtgt gatttgatta ccgttttgac tctcatttaa ttgtccattt taaaaatttt 199080 aactgaagtt agat ttaaagttca atacccataa aggatacttc tcaatagagc 199140 cgagaacttc caca acaaaaaaag ggcaaagttc aaaaaactaa gcatcaggta 199200 gctacttttt actgcccagg gacatgtcta ggtaaactgt caccatatcc atctacattt 199260 gcttgctagt agagcttcca ttttctactg caaaatagtt tctggaacca cttccatgtt 199320 ggccaaaaga gagtgtcaac aattcctttc caaaattgac ctttagaaag tgaatctaaa 199380 Page 134 715825 ‐ Sequence Listing.txt atgtttgatt caagtatgtg aggggagctg catcaaagtt ttcattttta ctacatacaa 199440 aagtgacaga taaatccgta aaatgtatgc atttttctgc tgct aattaattta 199500 aaaagagatt gttagaataa aaggtcagag agtaaacata ttacagatat ttattgagag 199560 gtgt gcagagttgg aaaaaataaa ttgc tcctttcaac agacttacaa 199620 tctaattgag ggagcgacag cataaatgta tgcaaagcaa ataatgcaag atacagcata 199680 aatt aactatcaga tgagtgacat atataataaa taccattaat tcacaggcaa 199740 tcgtaatcag aagcacttaa cttactatgt gccaggcatt ctgctcagta cttcacatac 199800 attatttcat ttttttgaaa tattatttct actttataga tgggaattgg tctt 199860 ccccctattc tggagaaagc aaggataatg gtgtaaggta gacaaagacc caagcagaca 199920 tgttggtctg gggcaaaggt ccatttaagg agag aaatgaaccc tggggccagc 199980 attagtctgt ttacaaccat atcccagtgc ctagtatagt gccttgcaca taataagtgc 200040 atat gtcttgaaaa aacaaatggc cctctggtct gtgcctgtaa tccagatcaa 200100 gtaccatgga ttaa ttagtgaatt aaagccacat accacatagc ttaaggaccc 200160 atccccaaga cctcccaatt tatg acaataaagg gtgg aaaagataca 200220 tcataagggg aatagcaata gcaattccag ctcactgggg tcat ggaatctgac 200280 atggtgaaca gttcataagt ttatttccag gctgcaagac cctgcaacat ctggcctctt 200340 gcacctccac aacctcaaat ccttctattc ttctctcact ctctctactc ctgccacaca 200400 tacctccctt ctactcctca aacccatttc agggcctata ttcttgcttc atattgcctg 200460 gaatgttctt ccacaaaaca tctgtgtggc tcattaccat accttcagat ctataacagc 200520 cactctcccc acatcttccc agctgcctga cattataata tatt tccttatgtg 200580 ttcatccccg tacacactag aacatgggcc ggca gaattccatc tgctgttttt 200640 gccattgaat gcccagcaac taggacagtg cctggcacat tgtaagtact cacacacagc 200700 aactctaact caggattact ttttctagct ctgaaatacc tacttccaag agaacgaaat 200760 ttattcaaga aatgttggat ggaaattgaa gagtgagctt ggaaacgaga cacagagtgg 200820 caggagccca gaccaacctg tttatgaaag atgcctttgc aggg aaaaatacac 200880 cttaaaacct ctgccaaagt atatgctttc ttaggacacc atgc tgaattgcac 200940 Page 135 715825 ‐ Sequence Listing.txt ctggtctgaa caagatctat gaatttgcca aaacaactaa ttcctgtgat ttaagagtca 201000 ctactaccag ccta gtaaacaagt caac gagcaccaca agta 201060 tccaaagaca ctgc tgcatgcaaa accagacaaa tgcattcacg cgggtgacag 201120 tgagtggaag atct tatttttatt attttttccc ttatcaaaca ctagcaaggg 201180 actagatgtc ataaatctag ttaaaatatg ttgactttgc ctcaaatttg agcattcatg 201240 aaag gacacttgtt ataggatctg atgatgtact ttagaatctt cttttgtgca 201300 aattgagact tcagagaact caaaatatat ggtaaattca tatt ataagtaaaa 201360 tgcc tcacaacatt ttttgaaagt taaatattta gtaattttac aaatatgtat 201420 tgagcactcc ttaa atgc taatgctgtg atggatcaaa aggagaataa 201480 gccatgatcc ttaccttcag acttcaagct tattattcat tgggcagtta gataactaac 201540 gaca tggaataata agtgccattg tccagatatt aaaaacaaaa ttggtgttgt 201600 ggaagcaaaa agaatgtaga gatggatccc gaga aagaaaaatt gcttcctaaa 201660 gaagacacag attgaccatg aaaggtggat ggttctacac aggactagaa ggtaggaatt 201720 cttcatttgt tggacttgct aatttttttt ggtgtaaata tacccactgt tgttgattta 201780 aagttgataa cgtgatgcaa ctgaacacag aactgggaag agaaggtggc tccagcacgc 201840 tacctatgag tcaccagctg agctccagac ttaattaaat caacctcctc actactattt 201900 tgaatgagtg caag tcttaaaaag atctatgata acattataag ggaagagata 201960 gtcacttctg tccc ttacatctcc atctcacctt ccaatattct gtttgaatat 202020 ccttccaatt tcagtcatat gttcctggct ggcctaccta ggattaatat tggcccagtg 202080 ccaaaatgtg attctattta ttccttttag cattgctgtg attaatctgc gctcctgtta 202140 tcccatggca tagcaaactc tcttactgat tatggcctgg tattgacacc tctgctgttc 202200 tccataacga aaagcagctt ttggggtggc tagctgggca ggatgttttg ctgctcttgt 202260 aacagtagga aggaaaagct ggaggaatta ctgggaagct ttgcagaagg aagatacagg 202320 ccagctgaga gccagcattc atattgcctg ttcctttcag tattctttgt gaaaacacca 202380 ccaccaatgt gttccctgga cgtcactact gcacctttaa ctggccttat tatgctaggg 202440 actgcatttg aaaagccaaa ctctagtatc tgtctgtaat tgcaagcgga tatctcagca 202500 Page 136 715825 ‐ Sequence Listing.txt catgcacaag cttatgtcag gaggatgttt atgaaaaact caccaagcag aacactgcta 202560 gacaggaaat aaatatgtga agcttgaagt tgttaggaaa cttccacatt tgtccctcta 202620 agccagagat aggacctgtg agaaaagaag gtctttatca ttgcgcattg attcttgctg 202680 aacccctgct attctcaaaa tacatttaca gcaaaatgtg gctactgcag atgtatttaa 202740 gctt ttttaaatga ttta aagt ttgttatcta ctattttact 202800 gtaaagcatt aaaaagtgtt tgaaaccacc attt cacagttcct gttttatttg 202860 tttaaattct ctagctcatg gctg tatgatttac tgttcaagta gagaagaaat 202920 acactccctc atggagatgt ggggaggtaa tactgtctct tggaagggct cagagatttc 202980 ctgtttagat tacacaggct tctttagagc tgccaagagt cataacatgt acgagataat 203040 acactttggt tcaggaaaaa ctatggatag gaatgtaatt aattcactga gccacaaaag 203100 atattccagc ttagaaatgt cactgcactc aggcctggtg gactcagtat gccaaggggt 203160 agccatgacc aaaaagagga ttgctgcctg aggacccact gagtagtatc caaccacaga 203220 gcaaaaggag ggggcctggc tgctaaggac atcacacgtc tcacctgctt ctttgagaat 203280 tgatccctga agggtatttc tgcccaaagc ctcagcaacc tggcttcatc aatataactt 203340 tgtgatgctt gtgacattga gatcaatcaa tcagcatgta ctttatcaag tgcctcctca 203400 tgagtaccaa ttgtggcaca tagtggggaa accctagagg cagagccctg cagaggatat 203460 ggtgattctg accagagcaa gaaggtatag tgaaaagttt tata ttttgtgtct 203520 tgtcataaga atcacctggc agggaggggt atggaagggc aaggtaagca tacacattcc 203580 caggaccttt ccaaaatgta gagtgaccag ggacttagag attcagactc tctg 203640 gggcagggcc ttgg tatatttaat tgtg tgaggccctt catg 203700 acctcctgta tagc ttggttgctg gtac tatgtttact tgtgtttgca 203760 ctgtctattc aggggtgttt ctaaatgcca ttgctacaca actggtgaat tatgattctt 203820 gccagaacat tgattctcct actcttgctt ccttaatgac acactagaga actgggattg 203880 ttta gtctcaggat gaatcattgc cataagtaga tccc ctactccacc 203940 aactcatttg ccaaacaccc ttaaagaaca gaacccactg cctacatgca gcctgcacca 204000 ggagggccta aatggtctag ctgggtttat gacaacatcc cgtcttcaca tcagcaaaac 204060 Page 137 715825 ‐ Sequence g.txt cctaagtgca caaagtctaa caca atgtcaagtt ctccatagga aaagacatgt 204120 ccctgctgtc gtga ctagcaataa taataatgac aaaaacaata acaatgataa 204180 gcatatataa cacttactta tcactaatta tattgtaaat gaaatgattt gcatgtacta 204240 actgatttaa atcttatata tatatagata cttttactct ctcaatttta gaga 204300 aaccaagacc tagatacgtg tttctgttga gaagttgagt acaaggttga gtgtaagtag 204360 ggaaagttca actgcagtca gttctagtct tggtaagtac actgtgaggc cccc 204420 aagcatagca aattaatggt gtgt aatc aaaattaagt tctttggcta 204480 ggttctccct gatgtgcccc tgcttcttcc ctaattcaac acatccccag ctccatccat 204540 gcattcccaa cacatcacag ctctttacat gcccaggctg tgtcttctgc acctttgtac 204600 cttctgcacc tttgtttcct tggccccaac tgccctttct tttcctccac attacccttt 204660 atcccaaatt tagcacctgt ctcaaggagt caccttccca aggaagtttc tttg 204720 ttaacagata ttccattgtt cctccaatgc ttgaccactc ttcctttata gatccctgcc 204780 tagaaaaatg tgggctcact gaggccaggg gctgcagcta gtttatttta taacccagca 204840 tttaaaagtg tatt gatttgttgg gaatagttaa taaatggagt ccttgcagat 204900 cataaccaag accacagttc gtaatggttt cattaacttt attg gatgtgattc 204960 tctgcttatg gtcttccttt acttgttttt cccttactgc tcagcacctc tagacattag 205020 gtacatggct ctgatgctaa ttaaaattga tgactgagaa tgacacttcc atttgctaag 205080 ccagcgcagt tttgttcatt gtgctttact ttttaaccag cacccttagc ataaatctgt 205140 agtctttcca tgagggtacc atttgttcct tttatgtctc gattcattac tcag 205200 gactgttagc tgactaagac tttttgcttt gtgaaaatgt caccaaatgc acgataaagg 205260 caaagtcaca ctgt ttgcaaaaag aattaaatgc tggtttgtga agattcaagg 205320 ctggccaggg ctccccaagc atttccaggc tttg gctctgcact agga 205380 tctcataact gacccccaca ttccatttct gccatcgtgg aaaaatttgt caactttact 205440 gctgatgtta ggcctggaaa ttgtcatcca ttagttttct cagattcaag ctgaaaattg 205500 agacaaactt cctacgtaat caaa ataacacata tgtttatgtg ctatcccatg 205560 attaacatat ttttaaaacc actttattga ggtatggttg gcatacaaaa atctgtgcat 205620 Page 138 715825 ‐ Sequence Listing.txt atttaatgta tacagcttca tgaatttgga gataagtata catccatgaa attattactg 205680 catgtatgcc ataaacctat cacctacaaa aatttccttt cactttgtta ttattttgat 205740 taacttaatt tttttcttcc ctat caaaactttc tcaagtaata catagttgtc 205800 acaa acttactgaa ccttgaccaa aggtcctctt ttagtgctca tcttagagaa 205860 agaattaatg aaacaaagtg ttctctgatt tgtagcaaag atctgtgatg gtggtgggaa 205920 tggttctaga tggt aataataaaa acttagagta tcaaagcagc aagtagattt 205980 gaaggaattg ttacaatgca attttgcttt cccgccactt taaaatcaag gtgtagtact 206040 ttatttactt aatg tttgcttttt gtcataattc cttattgcat atgagagtaa 206100 atgatctata gatgaagata aaat ttagagagag aataaaaaag tttc 206160 acagctgaaa ggctgcttcc cagttagcta actgggagga gttactgaaa aagtacattg 206220 aaaagcggct caggggcagg tgaattggac tcaccaggct ctgacattca gagagatggg 206280 tcag ctcactgtcc agcacatctt tattttattt ctctttcttg ttttatatca 206340 gaaatagatt tcttggcatt gttactgtgg gtttctatta aggactgaaa tatt 206400 aataatctga gagtatgtaa aaaaaaaatt cattttctcc tactatactc tcataacaca 206460 tttg gtgaccagag atcaccaaaa tgtgtgtggt gtcaacgaaa agagtcaaac 206520 tctctaaaat atttgaagag attttttctg agccaaatgt gagtgaacat ggcctgtgac 206580 atagccctca ggaggtcctg agaacatgtg gtgg tcagggtaca gcttggtttt 206640 atatatttta gggaggcata agacatcaat caaatacatt atac gttgatttgg 206700 ttcagaaagg aact caaatggggg gcttccaggc tataggtaaa tttaaacatt 206760 ttctggttga caattagttg agtttgtctg aagacctggg attaatggaa aggactattc 206820 aggttaagat atgtttctta ttggacctaa aactgtgcct ggctcttagt tgattactgc 206880 ctggatctgg gaaggaagga aggaaaacaa agggggaagg ggattctcta tagaatgtgg 206940 atttttccca taagagactt tgtagggcaa tttcaaggca tggcaaggaa atatactttg 207000 gggctaatat tttttccttg tctcataatg ttatgccaga gtcatattga aaagcaagtc 207060 taca aggtcaaata atcc tgatgagaac ccatggtttg tagggcatga 207120 ctccccagaa cccttaggta ggaatttggg caagataaaa aatcggaact tagtcctcgg 207180 Page 139 715825 ‐ Sequence Listing.txt tctc tccccacaca aattctccaa cagattcttc agtgggacac caactgggtg 207240 ttctcaaatt caattcaatt ctgacaatct acctatctac ctggaaatag catcagataa 207300 ccacaggttt acggctcatt ccaacaatac tgtcccccac ttcagatgcc aactgcaagt 207360 aataggttgt tacctatact tctagccagt cagctgtaaa ttggtgttcc cacaacctcc 207420 ccctccggtt tgataatttg agacagcttg tgta ccagcttatt agaaaggata 207480 ttacaaagga cacagatgaa gagatggata gggtaaggta tgtgggttgg agttgcagag 207540 tttccatgac ctctctgagt gcagcatctt catgtgttca gctatccaga atctctcgga 207600 ttaagacatt ggccactggt gatcaaatta accttgagtc cctctcccct tcctgaggtt 207660 ggagagtggg gctgaagtgt ctcaacctct aatcaactct tggtctttcc tgtgaccatg 207720 ccccatcctg tcca ggagccccca ggcatcagtc aactcattag catacgaaag 207780 atca ctacagagat tcgaaggatt ttaggaactg tgtcaagaaa cggagacaag 207840 gtcaaatatg tatttcacaa tatcaccagt agtttcactg ggaggtaaaa gttt 207900 actgtgggcc tgagccatgc tgaccctcta actt agaggtaacg tgatcagatg 207960 tggggaattc tggagaaaca cctttcacca ccaagcccag acaagagatg catacttttc 208020 tagctgggat aaag caacccactc taatacttca aggtagagtg acactacatt 208080 catcattttt cattttttcc ttat gccatctact actaatgtca atcaaattac 208140 gactgtgttt atagtggatg aattatggac acac cataaagttc tgtttctctc 208200 atgttgagct ctcc cttcattccc cttc caggatcatt cacatgttta 208260 aaaa taaacttttt ttactgaact ttttttcata ctgtttaaaa agaatttata 208320 tttctcttca ttcttacaga taagattcaa gtttaaactc aaataatgta cttt 208380 ttttaaaaaa ttgttcccta ctgtgtctag gcgtgagacc aaaagtaatt aagaccaggt 208440 tttcatttgc tgtgatttgt gtgagttctt ggtt aggtgcaatt ttaattttta 208500 aaagggggat tattatgaga ggagaaatca tactttatca tttgaaaatg atgccataac 208560 aggtgttagc agaaaaatca aactgtaaaa tattttaaag agatttattc tgagccaata 208620 taagtgactg tggccccatt gaaatgagcg ctga tccctctcac agagcttgcg 208680 acagggatgt ggctcacctg ttcagttgcc ccactgctca aacccctagg gggagaatac 208740 Page 140 715825 ‐ Sequence Listing.txt tcag gtgcaaaggc tggggcaagt gccttggccc ccct tagccccgag 208800 gtagtgtcta ggggtggggt gcctgcaacc ccagtgttac aaagttcttt cagctttgca 208860 gtccacggac agcttgagtg ttaatcagct caatggaccc tctgccttat agcaaaggca 208920 gagggccagt gtgacagctt tctgtatccc aagctcttgc ccagtgtcct agaaaaaaca 208980 acag gggctcgaag gatgagtgca tatt gagtagtgga ggtggctctc 209040 agcaagatgg atggggagtg ggaagtgggg atggagtggg aaggtgaact gaag 209100 tcgggcagcc cagtggctgg actcttctcc aacctccccc aggcaagctc ctctcagcgt 209160 ccagatgttc ctcttccctc tctg ccgcatcatt tcaccatctg tctgctggtc 209220 agctggcttg ctggtgtgct ggtctgttgg tctgctggtc tgga ggtt 209280 cagagtttat atgagtgcac gatagggggt gttttgggcc aaaaggtagc gaca 209340 tgaaaacgga aatgcctgtt cccatttagg gctgcaggtc ttcaggcttg agggtggggc 209400 ctttgcccag gaactaccct cttctaccca gtgtttccct gtctcctgtc catatcacca 209460 gtattcacag tctcaaggag tcttgagaaa gtgtgcccaa ggccgtcaga ttcagtttgg 209520 ttctgtatgt ttcagggagg caggaattac aggcaaagac ataaatcagt aagg 209580 tatacattgg ctga aaaggcagga tgtcttgaag tggggacttg atag 209640 tttggttcag agattcttta atctgcagtt ggttaaagga ctgt acagaagctt 209700 cgagttagca aaaagaaata tttaaattaa gataaggatg ctatgtcaga gtcagccaca 209760 aaatgacctg tttagcaaga ttaatggcct ataggtgtga cttaaccctt gccttgcatg 209820 gcctaaggtc ttgtttataa tttagtatct tattgcccaa agagtctatt tagtcagtct 209880 ctct actttaacat taatgctggt cacttgtgcc taaactccaa aggggaggta 209940 tatccaacct gccttcccat tgtggccagg aacctttctc tggagtcccc ttggccaaga 210000 aggggtccat tcggttggtt tgggaagctg aggattttgt ttttagttta cacagggtca 210060 tatcagattg ttttgatggg gatgactaat ggttttcttc tctttctgtt tcagccacag 210120 cagctatcct tagcagagca ccctggagtc tgcaaagtgt taatccaggc ctaaagacaa 210180 gtaagaattt cagtcctttt tcttccttca atgatatttt ccatgtttta gtgtaattaa 210240 gctactatcc tttctctatt ttatttggga tggtagtaac tggaatagtg actgagttga 210300 Page 141 715825 ‐ Sequence Listing.txt aattttatag gcaagcaaaa cattttttaa attt ttct gatatagttt 210360 ggatgtttgt cccttccaaa tctcatgtaa tccccaatgt tggaagtgga gactgggagg 210420 agatgtttgg gtcatgtggg cagattcctc atgaatggtt tagcaccctc ctctttgtgc 210480 tgtcctcacc atgagtgagt tctcatgaga tgtt taaaagtgtg tggcacctcc 210540 cccttcaatc tcttgctccc actctcgccc tgtgagacac ctgctccgct tcaccatgat 210600 tataggcttc ctgaggcttt caccagaagc agatgctaat tgca gaactgtgag 210660 ccatttaaat catttttctt ttac ccagcctcag gtactttttt atagcaatga 210720 aaacaaacta atacaacttc tgtgcaaggc tgcttttttt tctatttttt gcttgtgctt 210780 ggaggttaag taaggccaaa ttaatgaagg aggaaaaaag aggaaatgat acatcatgga 210840 tcaacaatta gaat ttaggaaact gcctcttttt ataaattctt tttaaaatta 210900 ttttcattat tatcttgaag tatttatcta aggtttacac aaag ttaaacttgt 210960 ctctccaacc aaattgcctt aagcttcaaa attatgcctt attgtaagct ctttcttaac 211020 cttaaaatga ctttacacat tccccgctgg tcctttgaca atctcctctt caaccacaag 211080 cccc accatcaact ctgtggggaa gcgtctccaa attctctagt cctgaacaac 211140 attctgcctt ctctgcttcc atggaacttt taca acatgatagc gtttgcctcc 211200 ttta gtgtgtgtgt tagccctgca tatagaactc accagattgt gtggactgca 211260 tgaatgaatt aattctattg aactttaagg caaagcctaa actttatgct tcttctaaat 211320 cccttacatc tcctaaaaaa attctgatcc atagtagtag gtacttgttt aattaaattt 211380 tagggatgga tcat cagtggaagt atatgctaga atta tgcaataagg 211440 gaagggaaga cagtgtacct aaatcagtta agatattgct attcttgttg ttattctaga 211500 gtcacgaaat cataatttga attttatgac taaattgcag aattaatttc caatgtgaga 211560 ttttaacatt ttgg aggtgaccaa aaaggagagc tggtactgtt tttaacaact 211620 gtcattcaat tgtcagttgt gccagaccac aaatccttta tagccctcct gaag 211680 catctgacat gttaagctgc tccctaatta acacagaggt tgtaaaagaa gtggctgttt 211740 ggttctgttt gggtttccca gccagtatat tccaaagcct tttttcactc aacagatgag 211800 ttatgtgctt tatattctgt aaggaaatga gaagtaatca gttgaaaatg tgttactaat 211860 Page 142 715825 ‐ Sequence Listing.txt ggtacatgct tcacattgaa ctcc tgacacaaac ataatacttt gccctccact 211920 gtcccccaaa gtggcagtag gatttctcta agtaattttc tttacttata tgagtgcagg 211980 atagggggtg ttttgggcca aaaggtagct ttttggacat ggaa atgcctgttc 212040 ccatttaggg ctgcaggtct tcaggcttga gggtggggcc tttgcccagg aactaccctc 212100 ccag tgtttccctg tctcctgtcc atatcaccag tattcacagt ctcaaggagt 212160 aaag tgtgcccaag gccgtcagat tcagtttggt tctgtatgtc acagggtcta 212220 agaagcgtaa acattgtgtc ttgttgaaat acagcctcta ggtatggagg atgtgttgaa 212280 caacttccta ccagtcattt ggcatatgtt gatttcctgt cttcatgata cgtaagacga 212340 ctagctaatt atcattcata tgtggtaagt gata ctgacttccc ctatctttcc 212400 agctttttct tatcaaaagt cacctgctct ctgtcccagg aacgactggc taaagtaacc 212460 tatatcagtg tctgtaacag tgggcaccta tcatagtgca catgcttgaa catatcattg 212520 ccttttatca tcacgagcct caga tgtgacagac tcaagtgctc acatcacctc 212580 actctgtcac tgtatacatt gttaccgtgt cacaaatatt taacagtctg ctgtgtactc 212640 agtctttagc tgtgtgccct gagggagaca gagtaagata ctgccttgac atcaaggagc 212700 tcacattctc gaga taatttcaca tgaaaagtta gtgtttaata tgaaaagtta 212760 gtgtttaaca tgaaatgtcc tgagaatata taat ttacacgttt cctgtgtgta 212820 cttttctaag ttctcagact caaaacaaag ccccatggaa gaaaaaatga aataaaaacc 212880 ctgtcaggac aaatcctagc cagaactgac caaacataaa atgc cactgccctc 212940 tccaagctac ctttacttta tacttgggtc caagaagccc aaacattgtg cctcattgaa 213000 atataacctc taggtatgga ggatgtgttg ttcc tcag tgcagtgcag 213060 tgaccattta gcagcatctc cctcctctct ccttccaccc ccat ctctccttcc 213120 ttgcatctat cttcccctgc caacaataat tttcttatgt tctaagtaaa tagt 213180 gctctcccta ctacctaaac attaaacttc aaacctttcc caagaccctg aacacccacc 213240 ccagcttgta agttcaggct catt ccccaggcac actgtatttt ccctcctctg 213300 gtacactgct catgtcatcg aatctatctt cctcccaccc catcctggat tctgtaaata 213360 taaatcagtc ctgcccacct ttaagtttca acct gatactcatg gcctgaagca 213420 Page 143 715825 ‐ Sequence Listing.txt atccctccct tctccatgct ggtctgagag aggtcatgat atttcagtag ctctggagag 213480 acacatatgg tcaaaccaga ccagctaaaa ttaacccatg ctatgcacaa cctaaagaat 213540 cacctcttgc tgtaacctct ttcttctctt gctcaccaaa aactgtctgt cacatttgct 213600 aagtaagccc ttagggcttt gctgtgctgg caaaaggtct taatccatgt gaatgtgcat 213660 ttttgtgtta gtgagcacat gctaacatgc caga ttagtttctt aagaaacatt 213720 ttctggggga aaaaagacct gtttttggtt agtaacccca aaaggacctt tcagttcaca 213780 tacgtggtag cagcatactc cacttatgca aaggtcagcc aaat atgggcaaaa 213840 acacagactt aggataagaa gaatgttaag ggagtttaca gtttaaagag atatccaaac 213900 aactttttta tattttaaag aagtaatgct ataattttac tacaaagaaa acttctttat 213960 atttctgggg agaagaatag ttac ctag agaaaagcaa aacattttta 214020 gtattcccaa ataagacagg cacctcaact agggtgctgt ggttgcacgt tctttgtagt 214080 ttttcaagaa ttttatttct tgat tatttattgg cagaagattt gttgggccaa 214140 acatgtaaga ctttcttaaa cacatataga gaaaaaaatt ttgc acatctttct 214200 gagggagatt tttcccctat ttttaaaagt cattgctttt attt gtcttgtatt 214260 cctataaaag tgtaaatttt gtgattgata gcatttttac atga tatc 214320 caactggagc aagttttatt gactgcttat tggagcataa attagtctaa atga 214380 aaataggcat ttgaacatga gtattaatgg ctgagatcag aggcaagttt tgaaaggatt 214440 ccaaaatatt ttag ataggcaagc aaatgaattg cttgaatgct agaagttcac 214500 aaacattcaa acaattgtga ttaa cttcaataaa aacttttgca ggacaaaaat 214560 ttaatatagt aaacttcatc ttgcttgtcc aggtccgtat acattcttag ctggactctt 214620 gtcctagctt cctaattttt cttcctatct cctatttttc cctattccaa atac 214680 tctgttcttg attaattctt cctgcctacc tctgattcag tgattcatct gcccaatcat 214740 ctatagtagc tccaaactct tttctaaatt atgaataaac ttatctccct ggcattcaga 214800 aaattcaaca gcattcatct tacacacttt tctagcctta tctccctttt ctcttatgta 214860 ctcctatgtt tatattccct gcagtcttgc ttcattatat ccatttacaa tgaccctttt 214920 accagtaatt tcctcttctt cagt ctgaaacaat ccttcataga ttttgtcctg 214980 Page 144 715825 ‐ ce Listing.txt tgagccatat ttcaaataca actttatcca tttg cccagttccc acaagaggat 215040 tctgcttttg ctttagaatt gtagcctttt tttcctctct cgcaaggaga gtag 215100 caccgcagtt taagtactca gcctctggag ttag tttaagaccc agttctactg 215160 cttacttcct gtatgatctt attt tatgatctct ttgtcttttt tttttcatct 215220 taaa gatgctaata gtacctacct cataagatgg ttgtgagaat tataagtgtt 215280 gatatattta aagtagttag atct ggccctacag taagcttacg tggtatttat 215340 tgtattctct tatggctctt attttattcc aatgtgtatt aaattgaacc gtatgaaatt 215400 gtca actctatatt ggaccctaaa atcattatgt cttttggttc aaccaaatgt 215460 agtgcttttt gcaccccccc ttaataaatt gaactatctc taaagatagg gacaatatct 215520 tacacatcat tatatcctac agtacctgct acatacttga catatgctga gtatttcacg 215580 gatggttatt gaattttgca cacacacaca cacacacaca ctgcaaaaaa taaacagaag 215640 ccaagccctc cccagtatct taagtactct ttggctacca gggagtttac tccatgctgt 215700 tcagcagtca tttatgaaag gagagtgata aagatataga ggaggagaat ttgt 215760 ctattgctga gtataaatac tatgcctttc cgaaaagcct tccacagaac ctttccttca 215820 ggtcagggac ctagtgtcat gggtcggtct tggataacgt tgcaggacat atcagttcaa 215880 ctgccaaggg aatcataaat agtcctactc ctgcctgcgg cccaccactg cctctctgct 215940 ttcattcttt tttatcagat attttcaaca tcaagaactt tgat aatttaacta 216000 gtat aacataaggg aaatgtgtcc tggcagagat ggcatcttag agtgaatgca 216060 cagtctttat tggttaccaa aaacaaaaaa aaaaaaactt gagctttgga caagcagtag 216120 agagcagatt tgatactggg ttctgacatg gaca tatt gacagtctac 216180 ttgtttataa actattcaat aaacaattta gtaagtaaac atagattctt gcaatccctt 216240 ttaaggaaac agtgtttatg ttggctctct cttgtaccca tgct cagcctttcc 216300 tgactcacat aagcactaat ctccagataa caccaagcac cctagggtta ttatttatcc 216360 cccttccttg ttctctgaaa taagagaaag gcaggttaaa ttatgcactt tatgtaagaa 216420 gaaatggagg tacagagaaa acagcttaag tctcttaaca gcccaagaga gtgaagaaga 216480 tattgccaat gcaatgagtt gtatctgtcc ctaggtaagt aaaatattaa ttaaagcata 216540 Page 145 715825 ‐ Sequence Listing.txt caactatatt aataattaaa acaacagtct ttacttatat ggactttgca gtgacttttt 216600 tccagcctga aatactcaga taatgactgc cattagtttc acacgttagt ttat 216660 atactgcttt gttttcacac aaaatcgttg agaggtaaga attttttgaa agaaatattt 216720 ggtcttaact tttttatccc ccttcaactt caagcaattt tctgagcaat gataagtggt 216780 aagtagatat ttaccactta gtttacaaga gacctgtttc tctctgtgca ttgacttagg 216840 cactattaat gaaacctttg gaatgcaggt cccttctggt tgtaaacata tactgaggtc 216900 ttctatttct tttggaactc aaacaataag aaaatagtta gaaatctgtt tgtgggcata 216960 ggtctctaaa agccttaatc ttagaagtga gtaaaaaaaa ttttaggcca gacgcggtgg 217020 cctg cagc actttgggag gccgaggtgg gcggatcacg aggtcaggag 217080 atggagacca tcatggctaa cacagtgaaa tcccgtctct actaaaaata caaaaaatta 217140 gccgggcgtg gtggcgggcg cctgtagtcc cagctacttg ggaggctgag gaat 217200 ggcgtgaacc cgggaggcgg agcttgcagt gagccgagat ctcaccactg agcc 217260 tgggcgacag agcgagaccc cgtttcaaaa aaaaaaaaaa aaaaaaaaaa ccta 217320 agaaggatga ttaagcatct tacttaaatt ttcagtatgc ctatgtacac tctatatact 217380 gacttctagc atggtttctt agca taacacacat aagg tcaa 217440 gacaaacatt ctttcaccct cccc aatgggtggt gaacactttt tagtaactct 217500 tgaaagttaa agcatccaac agttggttgt gacctttttg gttgtgacct ttgagttctt 217560 ctagcttgta gcccactgat ttgctgctta attccacagc acca actctaatca 217620 ctgctcccga gagagcccta gcttctgcac acatgagtct ctcaccagga aaggatacct 217680 gaagtccaga aaagcccttt gttcacactg gctcctccta gtggggaaca gtttttttaa 217740 ataatgtaca tttatgcact gggaaaatat cttgaattta ttatttaggt gtaaccagac 217800 tttaatacaa cttaacctac acactgagaa agcagacatt tacaaaaaga tttatggctt 217860 tgacaaagcg ttcaaatgta gttaccatta aatagtagtt caagtaattg tgtgtctcat 217920 ggcaaataca ataa atat atttaagcca aaaataacaa gaggtgatca 217980 aaac aaagaactta ttacttagga aaaaatgtta cacaactttc aaaggacttt 218040 tgaaaatata gtatgattta taggaaattt atttgcatat aattcacaat atctggtaca 218100 Page 146 715825 ‐ Sequence Listing.txt aggtaagcta cctctgtgtt ttttttcttt acaa atatttaaac caagggttgg 218160 caaacaggcc ctcagaccag gttt ttgtaaataa agttttattg accc 218220 atgcctgttt gtttcagatt gtgtttactt tagggctaca gtggcagagt ggagtagcta 218280 agacacagag cataggtcca caaacctaaa atatttactc tctggccctc taaaaaaaag 218340 tatgccaaac cattctaaac agcaaagcaa ttaattcttt tttttcaact cttattttag 218400 atttaggggg tacacgtgca ggtttgttac atgggtcaat tgcatgtctc tgaggtttgg 218460 tgtacaaata atccccttac ccaggtattg agcatattac ttgatgtttt tcaactcaca 218520 ccccgctccc aatcttcacc gtag tcccctgtgt ctactgttgc catctttata 218580 ttta tccagtgttt agctcctgct tataagtaag aacatatggt tttt 218640 ctgttcctgc gttaattcac ttatgatgat caca tacatccatg ttgctgcaaa 218700 ggacatgatt ttgttctttt ttatggctgc atagcttttc atggtatacg tgtaccacat 218760 tttctttatc cagtccacca tcaatgcgca tctaggttga ttttatgttt ttgctgttat 218820 gaatagtcct gtgatgaata tatgagtgcg tgtgtccttt ttgtagaatg atttattttt 218880 ctttgggtat ctacccagtt atgggattgc taggttgaat ggtagttctg ttttaatttc 218940 aaat ctccacactg ttttccacag tggctgaact aatttacatt agca 219000 gctataatat ggttgtttgt ttgtttgttt gacg gagtctcgct ttgtcgcctg 219060 ggctggagtg cagtggtgcg atttcggctc actgcactct ccgcctccca ggttcaagca 219120 atttgcctgc ctcagcctcc tgagtagctg ggattacagt cgtgcaccac cggc 219180 aaattttttt tatttttagt ggga tttcaccgtg ttggtcaggc tggtctcgaa 219240 ctcctgacct cgtgatctgc ccccctcagc atcccaaata ctatactgcc ccctcagtat 219300 aatatagtat tttaaggaac taatcatcaa gtttgtactg gttaccctct tttagtctcc 219360 tgttatcttc aatttcataa ttggcattaa tgacaataca gtgttcactt tataaatttg 219420 cttcatagta aactcttctg aaataaatta cagtcatgca tcacttaaca atag 219480 gttctaagaa atgcataatt aggtaatttc atcattgtgt aaacatgaag tgtactcaca 219540 caaacctgga tggtacagtc tgctgcacac ttat gtct attgttccta 219600 ggctacaaat ctatacagca tgttactgta ctgaatattc tcagcaattg taacacaatg 219660 Page 147 715825 ‐ Sequence Listing.txt gtaagtattt atgtatctaa acatagaaaa tgtacagtaa acatatagta ttgtaatcgt 219720 atgggacgac tatcatatat gcagtctgtc gttgaccaaa acatcattat acagcacaag 219780 actatagttg aaaattttaa attacatatg tgggttgcac tgtatttctg tttgcagcat 219840 tgatatatac atttaatggt ttgtatgttt gtgcttgcat tcataaatat taaactgtta 219900 cagggagcat attttcttgt gtaaaaaaat aaataatttt tatttctaat gacatataaa 219960 attattatgg ttatgtttaa agaggcttga agaggtatta tggttatgtt tgaagaggca 220020 acggaaacgt cacctttgtc attgaccaaa acatcattgt gtggctcacg actgtaatag 220080 tgtaaagtaa ggattcaatg tatcggctaa tcaatgtgga catatcattc agtattatta 220140 ctcc atccaatgaa gactgaacac ctgtaaatgc ttggtgatgg atggaaaggg 220200 caattatttg gact gtctgagacg catt taat ttaa 220260 tgaaggatca atgcaccata cagctccagt ttgagaacac acttgacatt gtagtttgta 220320 gatcttttat actg ctatcactga gctg aagaataaag acaaaagatt 220380 ctctctttag gtgc actttaaaga ctcataaacc tgaaacctca cagaatcata 220440 atagatgtat tttcagagac aatttctgag tccttgacat attctcaaat catg 220500 tcttcactgc ttat ctttttattt ttatctgtca tggaaaagca gccttttttc 220560 tttttttatc tcctactatg ccttaataaa tagaatttaa aaccccgaat ttgaattatt 220620 gtgaaagcca gtag caaatccatc tatgctctgt gttgtcagca catatggttt 220680 tgtgtacctg ctaccatgaa actctgccag ggttatcctc atgg agagacacct 220740 gatgccatcc ttactctgac agaagttttt ctttctgtga attccaaaaa cttttgaagt 220800 tatgcatctc ttgcattgaa cttcagtggc ttgtgtacac atggtatctt cctttctaga 220860 ttgtaagttc tttgagggca gaac ctttctcatc tttatatgct ctcc 220920 acccttggtt tagccagggc cttacaaaaa gtagaagctt aaataatgtt tattaggtga 220980 atatcatact aagttccaga aattacctga gagcaattga agaagggaag tgtggaggga 221040 gaggtgttag catagatttc atagtgtttg agtttggcag tttggcatcc ttttcctcaa 221100 cactaatact gacacagata agtaacctaa ctgccttctc aaatctgaga gcagtagatg 221160 cattttctct tttgggactt ttctatctca tgtgggaaaa gcaaacaaga aggtcctgca 221220 Page 148 715825 ‐ Sequence Listing.txt aaagtcttgt gggtatttat cagt ggttgtggca aactctctta ctggtttcaa 221280 ttggtcccac aggctatgtg atgaggactt tggggtttgg ggagctggga accatgagtt 221340 taag tatgacctaa catactgcta ataccccaca agcttcaatt tatccatctc 221400 gaaatggaga tactaacatc tatctcaaag ggtcattgtg aggagcgagt aggaacatag 221460 aaaagttcct agcacaaagt agatatggaa gaat aaggtgttag gtattttatt 221520 atttttactg ctgctgctgc tgttactact actgctatta ttattactac tcctggaaga 221580 gtaggacttg cctgggacac tgaccctact taccccttca cctcattcac ttat 221640 ctcctatata aattcatgta tatttttctg gaaggataag aaaaatcctt catctaggta 221700 gcgtattttg tatttgaata gtttatgttt caaatcccag agaaggccta tacagccaaa 221760 aaaa aaataaattt aaaaataaat attcagtgtt tcatatataa taaaatacct 221820 ttat tccatatcat atatgtgtgt gtgtgtgtgt atcttttaat tgccatgtat 221880 ttctaccaaa aaatacaaaa cttaattttg gaaa gaccctcgtt tgagaatccc 221940 tgcttttatg ttctgcttta gtccaggcaa cagatagctt aggttgtcac tttacaactg 222000 gagcagcagg tagggctgag aggctcgcca tactccaaat taccagtgcc agtcccatgg 222060 gaca ggaaaggcag gcactcaaac agaaaggtag tgcaattaat tgcttcaaat 222120 tctttactca gggctgccct tagtcatgat caaataaaat attg tttggcactt 222180 ggtaaaatgt tgtttccttt ccttcctcct gata gactctcctt aaaa 222240 aagatgaggc tgtacacaga gctaaaagtg tacacctttg aaaaaggtgt ctttttcaaa 222300 gagcaccttc accccttact ggactaaact caatccaaag ctcttttctc taagctttat 222360 aacacttact gcctggatga gtcatttgtc aataaataca gaatgtttgt ataggtgggg 222420 ttcttgtata tatgtacgag cccctagagt ctctaactta aaatttattt ttgctttaga 222480 agttcaggaa taaggaggct ttgatgatca attttaacaa ccgcaatata taatacagta 222540 actaatggtt aggtgtccag gctagcccag ggcagcctgt gtgattcatg ctgctggtga 222600 gctg gctgggcgaa ctgg aattctgtgg tgcctaaggg agggaaggga 222660 atatttccca cactatctca tcctgccctc actatcgcta cccccaatct ctctctacat 222720 tctaccccac ctactttgct ttttctgtga aagaccagct ggggcaaata ttttggatta 222780 Page 149 715825 ‐ ce Listing.txt agtaaaattt gtcttgggta acttccctaa aatttagttt ttaattgaat aatcttggtt 222840 aatccatgag taaataagct tgtagagtat agtcagcctc actgtgagaa gctgacaaac 222900 cagaaaacca gaggaatata caccaattcc ttcctgtcct gcaaacctct gcttcttgag 222960 gtttttaaag agtgggtgcc atta gtcattagtt attgacagga ccaaagagat 223020 atgcctggct cctcttggaa aaaccaaaag actgagaggg aaaagtacac caaaaagata 223080 gagg cagactgcta taaagaaaat aattaggaga agaaatcata tgttttcaga 223140 tgaaaagaat ctgaggatga aaaaagcagc cttttcaggc cgatgatgga aagatagaaa 223200 ctaaattcag caga ttag aagggcaaga agtcatagaa gaccaagatt 223260 tcccaaatta ccaaaagaaa tcaagcccag tcttgttcag gctgcagaat gagaacgccc 223320 ttctagtaag atccgtacaa tgaatttcac aaatgttgat ttctttctgt cctctttgag 223380 cccataatca cctccttcta cttgcacaac cttgaccatc accactacct aata 223440 accagttctt atgttcccct caaggcataa cacaaaaata ttttctttat gattactttc 223500 tctacaaaaa agag agagagaaac aagtcagggg ttgg tgagtgtaga 223560 ccacagcaag aacctaaaat cctagtgggt tgttagtata gacaggctga aaccactatc 223620 ctgaagtggt ggttctaggt aggtatgccc atcagaatca tctgtggata ttca 223680 gtaaatacac atgcaggacc tctacctcaa atgtactgaa ttgaacttca ttgctggagc 223740 ttaggcattt catatttgtt tcctaagctg caaa caaa cttggtggct 223800 taataagaga aatgtattct gtcacagttc tggaggccag aagtccaaag tcaaggtatg 223860 accaggattg gttccttctg gaggctctga ggaaattctg ttccatgcct ctctcctaga 223920 ttttggtgac tgccagcaat ctttggtgtt ctttgatttg cagaaacatc attccaatct 223980 ctggttctgt ttga ccttccctat gtctgcgatt ggtctccttt ctgtctcttt 224040 taaggacacc tatcactgaa tgtagagcct atcctaatgc acaaggagct caattatacc 224100 ttaattatat ctgtaaagac cctttttcca actaaagtca tattcacagg taccaaggtt 224160 taggacttgg gcatatcttt ggaggataca ccca ttacacatat gcattgaagg 224220 gaaaaattca cgccacaact gattatccta taaagaatgt aact taacgcattt 224280 aacgcaccat agca cttaggaaat gctaggagat gcaaagctga agctaaatag 224340 Page 150 715825 ‐ Sequence Listing.txt gcttctttat tgcagaacct ctcagaggct ctcatctgtt tgtgtgcatt ataaatgtcc 224400 aagagaaaga aaagaatcac aacatttcct actt gaccagggaa cttcttttca 224460 agggattacc tgttaactac ctcaatggac actaatgact aaaggaatac atgctgctgg 224520 tgatcatggc acttccaaac tatgctcaat ggtgtgggca tgagtctacc acagtgtcta 224580 aacactaaga ttgttaatgt ctacacgacc tctccctgga tatgagcaca catccttcat 224640 caaatatcca cagtggtttc cctagaggat ttgcatatgt gcatggattt gtct 224700 agtctctact cttgtcttca gccatttttg tagagagaaa aaat attagcatga 224760 atggaaggga aaggtggcca agataataca ttatgccttt ttttttttcc acag 224820 atat ctgaaaaggg agaagtgact taatcatttc tattcccaca gtcc 224880 tacaaaattg atatcagtat atgattcatc cagagaagtt cacagtggta tttttttaaa 224940 aaaaactttt agaggttacc agggcatctc actattttaa aatttaatac ctcaagggaa 225000 ataagcaact accttgaatt tttgcatgaa ttgcatttga gaataactga atagttggtg 225060 gaataaagtt gtttttttaa aagtaggcat gtta ataaatataa aagaaatggt 225120 aggattagaa aaatcactac attacaaact ctaatgacat ttta agcaagatga 225180 tcagtgaatg ataaaatatt taggtatgct gtcttctagg tgaatcaagc tgacaatacc 225240 ttggacccac ctta ccacatgata ttatatgtct cctgatactt aaaataaata 225300 tcaaataaat aatt gttgaaaatt gttgatgaac atatagttca cagcaccacc 225360 catgatgtat tctttccatg agaattgatc tgaatcaaag tcta ggtctaactg 225420 ccagtgtgta ggaaatacca gggatagaga aacattttta aagtctttaa gattgcagta 225480 agctgaaaga ctgg tttctgcaat aacagcaaca aagttatgta ataagaagag 225540 agaa attt atacaaactt aagagacact gtgtgaatct agtttgtatc 225600 ctgatcaaac aaattaactg tcaaaagatg tcttttgaaa catgatggga aatttgagca 225660 taaactaagt attctacgat attcaggaat cattaccaat ttgttagata tgatgttggt 225720 atgttttttt aaatgagaaa gtttttagct tttagagata catacctaga tagttatggg 225780 tgaaagcata tcattaaaaa aaagatagtg gaagtacaca aaacaggatt gctatatgtt 225840 gataattgtt gaaccttggt gatgaacata taggaattaa ttaaaccata ttttctattt 225900 Page 151 715825 ‐ Sequence Listing.txt ttatgtttat tttgcaaatt ccaaaataaa aatagaataa tccctcatga acagatggtc 225960 tcaaatttca agta attc acattctcag gggaacccat gagaatatta 226020 tgaagtatat gtctatctca tata tatggaatcc taccattcct tttgtcttta 226080 ttactagtgg ccagagttct atcttgaaag gtgggaaatg tccttatatg aacagattag 226140 tttagagaat tattgtgaga aaaccagaaa gagt tctagctaac tggatattga 226200 atgagttgtg ctgaagtatg tggtcataaa gggttgataa tgaaatactt gctttccagt 226260 ggcaaggaaa aataaatgtc ttagaattta caaggtcatt cttgaaatca gtgg 226320 gctgaagatc tcattgcttc tgttatctgg cacgatggta tttgtttgtg cacagctctg 226380 ttgatgtgag ctatcaaata tttcttagag ctgaaatcat ctaatagcaa acattgctat 226440 gtcccaatgg agattccaag actctttggc acat ttacattcta tcccctttca 226500 tcactcctga acaaacaaaa acaaaaaaag gaaagataac caataggctt tttatttaat 226560 tgaaaaccaa agagagagag aggaaagaac cagttagttg ccattttcta aatgcaggct 226620 tgtt tctgccttct aattctttgc tcttgaagct atagctttca agcttgtgta 226680 tacaggccca gagagaacat ttgaaatgtg gccaccctac ccatgtccat cttc 226740 ctgcctttct ctctgcctac ttctgctcca ccatcccagg tcaggggctt ggaggctgac 226800 agcattacaa gtaatatagt cgttcaagct catataaaca agatgaaatc caaataataa 226860 ccaaaatgta ttttatttca ggac tactcagttc cctcagtttc gctgaccgat 226920 ttctaggagc cctaggctca gctcttggtt gtctcagaac tgaggagagt actcatttgc 226980 accatatgca tctgcttgtt agcctgtgct attg attcattact tggccttctc 227040 tgaaaagaaa aaca aaaatgcact cttaaaaata attattaaaa tacaaccagg 227100 aggtatgtgc atgg ctcaccttct accaaatcat actttatgat tttccacaat 227160 attatcttct attcctcctg cccctaaggt tccatggagc agagcaagtt gaagaatgtt 227220 aaggttttac taaactttta gaacagaggc tttggggaag caagagagag gtacactgaa 227280 aatgaagtgt ctgtctctgc ttctattaat gtcataggac tagaagttga cctcatagct 227340 aaat gaaccctgca aattgaaccc cagcacatgc ctctcattat ccattcttct 227400 agga tggggtccat gctcacatat caagaaaatg ttca gtctggctca 227460 Page 152 715825 ‐ Sequence Listing.txt ctgggtgagg ttttggcatg aaaactaata cgggttagtg tacatcaccc ataataaaag 227520 taaaagcttt tttttttatt tacccaggta aataagcaaa aggcagatct aaaatacatt 227580 agagttaagt tccatgggga cagaaatgtc tgctttgttt gttgttatac aattgacacc 227640 tagaatggtg gctggaccat agtgactaca aataaaatat ttcttaaggg aatgaatggt 227700 tctgcaggat agatgttctc tgcatttgga taagtgatga agac tcagagccta 227760 gatagaaaat attgtcccac tttcagttct gcaaactgac ttgaggtgct tggtgacgtc 227820 ctgcagcaag caaaccaaat gaaggcatct ctgagacccc atagtcacca ccagcatgct 227880 agcctcccat taccttgccc accctagatt ttcaaattgg gaatcactgt ggtaccagac 227940 tcgt gacttgcata ctttctcata ttggggcttg tgag atcttatttc 228000 cttttttggc agat ctgaaattgt tgttcagaga aggatattaa gacaatgact 228060 cttccattac catgcatttc tgttaccaac agaggaggta agtgaatcac ttaaaatgat 228120 acaattccat cagt acaccataaa catatcctta gctttgacta taattatagt 228180 atgtgggtga tgccgctgag aaaatggtat aattataaca ttatggttga gaattgtctg 228240 agtagaaaac actgagctgt actgtgcaaa gtttaaggcg gaattgtggg tcccttttca 228300 atatgaataa ttag ccaattgcaa ctgagagctt tgtgcaatga tattaataat 228360 ataaaaatcg gccgggcgtt gtggctcaca cctgtaatcc cagcactttg cgag 228420 gcgggtggat cacgagatca cgag accatcctgg ctaacacagt gaaacccctt 228480 ctctaataaa aataaaaaaa tatagctggg cgtggtggca ggtgcctgta gtcccagcta 228540 ctctggaggc tgaggcagga aaatggcatg aacccgggag gcagagcttg cagtgagctg 228600 agatcctgcc actgcactcc agcctgggcg acagagcaag tctc caaaaaaaaa 228660 aaaaaaagtc aagggccaaa gtaacaatgt aggaaaaatt tgatgacttt aatttcattt 228720 acttctagga catg caagcctaat gcagagtaga cacc aacttgaagg 228780 aagcatgaat gaaattacaa ggaaatctag aaaa ttaaccctgt agcttggttt 228840 ttccactctt tgctcttggc aaaaggatct tacgtatgta taccaaatgt gaaa 228900 attttgtttc tctgaatata gctttctttt ctctttaaca cactggtcca gtggttctag 228960 attttatgct cccataaatt aagtaagaca gcattctata tcatgactga ggtgttaatg 229020 Page 153 715825 ‐ Sequence Listing.txt acattatgca gttgtcacat tttgaaatat aaacttaaat tttt cactgtgtgt 229080 tctc tgtatttttt taaaaaattt ttaaagacca gagattttca gcaacaagaa 229140 acataaagaa gtaaaaagag cgtagaaacc ctgccctaga ggacctgctc caccacttaa 229200 aagccatgta cctcttgaag cctgtttcct ccaa aatt tttatattta 229260 caccctaacc atcacatggg tcacatgtga taacaatgtg tctt acaagtgttc 229320 taggaatctg taagtcttag agttctgagg tttattccca aaggacagga aattgtgggt 229380 aaac agttaaacag ggtggcaggg aatccctgtc acgtacccag gcctttgggt 229440 tattttctag ggtgagggga catggccagt agtacaaaga gcatgtgaac gcatggatgt 229500 gggtgtgtga ggtcatgagt gggtgtgtat gtttatgtac aacacatgta ttggaggata 229560 aaagggaaaa taatttgtct tcctgacttc ttctctattc ctggcttttc ttagattgtt 229620 attcctctct aaacaaagct tcaaaacaga aacccctccc cttctttatt atatcggaaa 229680 tctgggaatt tcct tgtcttatcc tactccctgt tctgttctaa atatataata 229740 acaataagta atagtactac tact agtagtagta gtagtagtag tggtggtggt 229800 agtaatggta gtaatagtaa gaggatgaaa agatggagga ggtgaattgg aaatagggag 229860 gtttcctgta gctgactgac agtttatata gcaaccgcct gcagatttag gttttttctg 229920 ctta ttttatagca acctcaacaa gctgtgacaa cctgcaatat ctttagccct 229980 taagatactg tctcttaaac ctgaccaata tttcttattt gagt aatgatagtc 230040 ttttctgtct gataagttca aaaggcacaa ctgattttcc taacattttc ctcaaatgaa 230100 gggagtattt gaaaaatgga actcaaatga ggagccacct cagaagccta actggagcat 230160 tgca tcagacagac ttggcttcag ttctgacact gatacttact agctgtggga 230220 tttttggaca agcttctcat ctgtaaacaa gtataaatac tacctacttt ataagctcgt 230280 atgaaaattc ccacaaagtt tagt ttcctttctt tttgtgctca gctctaaaaa 230340 tatgcagtgt agtgagtcac taatatttca taag ggaaaactat atacccaacc 230400 ctga gattcttcag aacatttttt aaagaggttc taattaggaa ttttataaat 230460 ggaatacaga gtacttttta aataataata acaatgatta atttaagtta ctaaacaaaa 230520 taccttaatg aatttgagaa aaataaactg aagataaata ttaattatta aaagagaaaa 230580 Page 154 715825 ‐ Sequence Listing.txt ttattaaagt aataacatgc aagtcacttg atacttgcaa agtaacacag aattagacat 230640 acat ttaagaggca gcaaagccaa aatggctggc cccctttaaa aggctcttgg 230700 caacagacat atggaaaact gtcatctctt ccctgggcct ttcttcctac tctggataag 230760 cagcatcctt cacacaaaag aacatccagg ataactaaga aagagatgaa atgatttatc 230820 ggaactagtt aaaataatta aatcttaaaa gcatgttctc ctgggcatag agtggggtga 230880 tttctgcaaa cattttgaaa ataaagtacc cctaaaacaa ggtt taactgctag 230940 aaaacaaggt gacaggttga gaaaactgaa aattttctta aaatcttgtt tacttgaatg 231000 gtgagccagc cacccaggga caga tcct ttaagaaata tagacttcag 231060 ttggaagaaa aaattagtag gttttaacct ttct gtga gaatattgat 231120 tgagcaccta ttattagaat aaatttatct taagtgaccc agggaagggt cgtgggtgac 231180 gggaactgtc aagaaagaaa aaaaatatgg atct taagtactta actg 231240 agggctcttg tctccatttt ccttagaccg tgatgttgct caaagtcaca taagagggca 231300 cataaattta ctgaatagta ttacagaaag cagcagtgac actgaaatgc ttgcattata 231360 ttcactatcc cagtcatctg cagttgcctg agggatttgc ggac aggaaaatgc 231420 tagtaccaac cagttctaga taaagaattt atttgctcca aaaactttca ctgtattaaa 231480 ttaaattaga ttggctggaa ttaaaaggta ataaggccca ttttcttatg taggtcatca 231540 attaatttaa ctctaaagat aattccaaaa gaagaggttt aaaaattgtt tgagtagtag 231600 taacatcatt ggaatttatg taaaacttcc caatgtactc acttttacag ataacatata 231660 tatatatata tatatatatg tatgtctatg actgctggca taatgatcaa aatgatcagt 231720 tttattactt caca tcaggcggca ctgatggttg aaataaaatg tgttagatga 231780 gcaa agataacata tagcaaatga aagtctttgt ctatgaagca catgattgtt 231840 ataattgttg ctgccctttt ctga accagattcc ccaaataagt caca 231900 gaatttgtct tgagcacttt catt gtaatccatg cattgaagta ggctttatca 231960 gcctacagct ataaactcca aggtgatttt aaagtctgaa ggtttatagg tcttcattag 232020 gataagctgg gcttaccata tatg aggactttgc tagaaaaata gtggaattgt 232080 tgaataggga aaagagataa tggtaacggg atttgcctga tgtcttcatc ctagaaaaaa 232140 Page 155 715825 ‐ Sequence Listing.txt agatttctgc ttgggcatta aggaccccag tgatgattct gggagacttt caggaatgct 232200 gacaaggctg gagctactca ggatttgatg ccaaagaagc cacactgcac atgtgttcct 232260 ctaaggtgta cttggttctc atctgagagg caaaggctct tttt aattgtttgg 232320 tcctaagtta ccttcaaact ccacctaacc acatctctaa tcctgtgtat tcca 232380 acatcttgta aattccaagg ggttggggga acctttaggt tccaaggctg agctaagtta 232440 taaatgaata ccctgtgcag tgttgagaat gaaacagaag ctttggtgcg tggtagccca 232500 ctgtgagtgg ggtttcaaag gagcagtcca ggggccctac atgaataggc atatatgggc 232560 caagagacag ctca gccataccat agtatactgg aacaatgaga aatgggagag 232620 gacatacttc ttaaagtgac acactgacct gttttcattc tctcctctct ctgcttctcc 232680 atttccactt attgccccta ttgcatctgt ccagtaactg taac agttttccaa 232740 actgacatta ttaatccaga agatggatgg tggtttttta attaaaagag aaagctgatt 232800 ttatttggtg ctgc tatcatcttc agtgttatat cccaatatga gtactttttt 232860 taatgttcta ctaaatccaa tagtatattc acctcactct aaac tcttggcttt 232920 aaaaaaatta gccagaaaaa aaga aaaaatacag tattttaaat aatg 232980 aactatatct taaaatattt gggggcataa ttcaattgta tccattttac tttaagatca 233040 tgcaaaaagg gaaaggtata gatgctattt tattgatatg ctgctccatg gatttcaaat 233100 tcaacatcat aagccaagat ttgtgggacc agaggaatgt tcaaaagtat aatctgatac 233160 attatctgct gcaggaatta agtaaaatat tgcatacatc tcacttccta taccaaatag 233220 agagaatgaa agtactagat ttac agatagttta gacaactata gggaattctg 233280 aactttcaaa cttttatatc ctaaactcaa gatttgggcc ttgaaaaata ataa 233340 aactgctaca gtgtagattt ttaaaattac gtgg tgaagttgac actttctgtt 233400 ggtatggcta gaagtcagat agatgcttaa tttgaaagac catgttttta tttcttctct 233460 ttttcttacc ctatgatttc attgacctga agtggctttt agtgccattc aattcacaca 233520 gaagccaaaa ttggttactg gaag aaaccaagat gttttattta gtttatgaaa 233580 cactagcaaa attt gatgcaaaac gaag ttttgtagtc attgaaagga 233640 gcaagaatat agactgcttg cagttccagt gtcgagacat tcattatcag atttaccact 233700 Page 156 715825 ‐ Sequence Listing.txt tgaaaatatt atcaagatag tatttatatt gtgtttacca ggtaaactaa gcactttagt 233760 tctgagcact ttacatattt taaatcatta atagtgctgt aacaagcctc tgaggtaggt 233820 actgttatcc ctctttaaca gataaagaga ctgaggcaca aggaagagaa gtgacttgct 233880 gaaatcacac acagctgaat gtggaccctg attcaaatcc acacatcctg actcaagcat 233940 ccttgctctg tactactgtg ctacagtgcc tctttacatc ctcctgatgt cttc 234000 ttctagaata atgagaagca actt tgaagtagga cttcctgggc atggtgcttt 234060 ccatctctgg gccaaagttt tctcatcttt acaaaaggat tacgatcaac ccccatctca 234120 tactgtggtt aggagaattg agcaagacca tatactaaaa gatgtcagaa cagggcctga 234180 atag tgcccaataa acattggctc ttgttatcat cataaatatg ttaaaatgag 234240 ctttagtatg tggataatag tagcagaatt tcctgaatga gacatgttaa acatttatta 234300 agcaggcact ttttggagtt tatcttataa taattcagta aggttactct tgtcatccct 234360 atttcactga atttgaggaa tctcaggctg caagataacg tattagtttt ctagaatcaa 234420 ataagcaagg actc aggatatatt gaccccaaaa cctcagatct ttctgccatc 234480 cctatcttgt tctaaacccc aggtttgctc gccc tagtcattga tcaaaaagca 234540 ccaatacaaa tcagagtaga gaaagtcata ttgagcttgt gaggttgtat tatgggcatg 234600 gtaacaaatg taattcagct gtattggcac agtgcataac aaccacactt aatttctgtc 234660 ctaagacctg tctgagccca taaataaagt aata gaat ggtaagggac 234720 cactcagaaa atcttggttg atataggaag tggcatctgt taat tgagagatat 234780 tgcttcttga gcta gaccattgct ctagggggat cctt ctctgtccat 234840 ggaagatgtg aaattcaaca gctgacctga ctgcttgtcg ctgttgatga aaaa 234900 tttcctctaa gatacgaact tcta gtccaaatca agtgaatatt tcctgttggt 234960 tgacctacaa cttcaagggt atgaggtcat aaaa agattccttt tctccccagt 235020 gttgtaagag ttattttagt tctatcaaat gctcccagtg agtactgcat atttcctttt 235080 atac attagctatt cactcttttt tcctatctct tctatgcttt tattttttcc 235140 ctcatctgtt taaccaatgg taccctgaat tttagaacca gacaggtagt aggacaaggc 235200 aaat gcacaggttg taaatttcag aatgcacatt caaattccat cgttgtctct 235260 Page 157 715825 ‐ Sequence Listing.txt tactaactga atgaatgtag gtaagatgct ttacctctca gagtcttact taccccatct 235320 ataaaatgag aataatacaa actgtcttct gtggttttct tgagcattaa acgtctctat 235380 ttatggaaca tagtttcaca tagtaactga ttctgtacca atgccctgcc gtag 235440 gcaaatgcat gtcccgaaag acccaaaaca agttgtccct cttttcaaga tttg 235500 ctcc ttaaacttat ccagttctgg tgtttaattt cctttataag ccagaagttg 235560 ttttacgtct caccaaatct tataacatga atattacact gtcttccaaa tgtgagcctc 235620 taattacctt aggccaatag cagagcctct gatcttgtct tttctccttt tccgcttacc 235680 agacagcaca ttctgcctga agac ccaaaaagat ataaatcaac tagggggcaa 235740 aaatggagtt tcctaagctt gtcccagagt ttgactcagt agcctgaggt ggagttcagg 235800 atgt taaaaacaag ctaccccagt ggttttgctg caggtggacc agactcccaa 235860 gaccacattt tgcaagcact ggcatttagg aagagcacgt acctactcta gcagagttta 235920 tgcagactat gattgcagcc tagtttgtgc agactattga ttgcagccac ttggcaaggc 235980 tctataagaa aaagcgagcc taag atca tggccttgaa actcctcatc 236040 tgaaagggtt tcctctcatc ccctcatccc cttgtgtctg cccctgaatg ccagactatc 236100 ttctccagcc ccaagtcaac ctctcatttt taagccattc ctcc tatatagtcc 236160 aaaatagcga atacattttt aggaattctc ttgctttatg gacgttcatc caaaaatatt 236220 tgag tgct atcc tgtagtgtct ttctgctcta atatttgggc 236280 ccttcctttc cacatagttg cattttcttt gacgggcaga tgctgctcct ttaatatttt 236340 tcacaccttt gtgcttctaa cagagcaatt atttcaggat gagggcactt ggagagctgt 236400 aagaggataa ggagcccagg gctctgcctt ggatttgtgt acctaaatgt tacctaatta 236460 cctg aggaagatgt ggaagcaaag tagaatggaa cagaaagtgt aata 236520 agaatttgga cattgctgct ccgtggtgac attggcagac cctc ttgcctcatt 236580 ttattcattc atgtatgacg gggttatgct cagtcataag tcactaaaat ttgtattcta 236640 catcccatta gtaaagtaat ttttgaacac atgatacata tgtttacata tttgtaagtt 236700 atatatatgt acaaggttct aatatattct gttcattgtc aaacataaaa taaa 236760 tttggtttaa tataaaatat aaaattggca ttagtagaca ctgtctaccg aaatgagaca 236820 Page 158 715825 ‐ Sequence Listing.txt ctgtctcatt tctgaaaaaa gcacaatgta gtta aaggttcatt cttaacagca 236880 gtaggagtag atctttattt caaatagtct ttgggataat ttcctatttt ggaagacagc 236940 ttatcagatt tggttagagt tgatgaaagc ttattctagg gttaagaaaa gtattagccc 237000 tttc ttattgttga cttg cataattagt tttaccttca gtatgaagtt 237060 catg aatcttttta actcacttat taca agtt aaatcaattt 237120 taaatcagta taatctatcc acaaaatcag tcatacagaa cctgcaaaaa acatgttcta 237180 taca tgaagaggta actaaagata ctacaaacaa cccctctgaa cggtaacact 237240 cccactcttc ctgcaaaatt cctctcatag caaatgcaac atgtgactca gacacaggct 237300 gactgaaggc tttatgcaac tcttacatgc tcaatattag aaaactttca tttgtttcct 237360 attttatata aacaacacat ataaataaac attttagtat atta cccagtggat 237420 tgtcttgcat ggtccatttt gaagacagta aactgtagcc tctattttta tttaatttca 237480 tgtt tgccaatatt cacagccagc tcttgttaat gttcttttct tgaa 237540 tcctgatgtc gtatcttgca acatcacctc taaagcctat ctttgcactc ctgtccatcc 237600 cccattctct attattatgc tgcctctgat ggccagagaa aaaaatcttg aaaatatata 237660 ttgtattgcc ctacctggcg aggaatcagc agttatacaa ttcaaagttg cagcaattca 237720 ccacattgtt tagcacccta ctatgtgtaa ggaggaagct tgatttaaaa taca 237780 atcatgcctt cttcaagaat gttttggagc atgcaagagc ttaatgctca tggacattta 237840 ctttattcca gcaaatttag acccaatctc tgtgtagttt cattttgttt tccatttcct 237900 gattaactga ctatatatct agctacttat ttgctgccat ctagtgtaat aaagtatgtt 237960 gattatacaa ggaattttga gcccattatg tagttgaata tcagtactca aaatgattct 238020 ttttttctgg tttcttataa gtttacaaaa tgcctagtca gggacctttc ttatcactgt 238080 aaccctgaac atggtcttaa tcttgtgtca tagaatctag ggctcaggat caaccttcgt 238140 tcattttcta taaatgtgac atttggaaac tgggtagggg cttagcagtt ggtggatatg 238200 atat gtaa tcattaagag atcatctcag gacc atgatttttt 238260 cctcatggag aaac acagcatgga ttcttaccag tagtgtgacc atgggcaatt 238320 tatttctctc ttggaggcat cattttcttc atatctaaaa tgaaatggta ggtccaggtg 238380 Page 159 715825 ‐ Sequence Listing.txt aagg ctag ctctaagagt ctgtgtctac atataaatga ttttctctgc 238440 agtg tttttagagt cctttttaat gccagaaatg aatacggctt ctctagttct 238500 tctaagtggc tcct ttggtgatgg ttagaagtaa gcagagatcc tggctagaaa 238560 gagagagagg aaaatgtgga ccatgatttt attcctttta ttcttgagag ttgtccaatg 238620 ggatattgtc cactagtgga taagtagata cttgccaata tgcacctgac ctcttctctt 238680 cactcataat gggaatttag aagtataata cctgttataa tcaacttcct tatc 238740 ccttttttgt cactctattt cctactgtaa cttctctatg aagtactata agtctacagt 238800 aacatactgg tgtttccctt tccttatgaa gttttatata gctactccag tatatcctaa 238860 aatgttcctt tttcttgctt tgga gtcttgcttg ttggccaggc tggcctcaaa 238920 ctcctgagct caagtgatcc tcccacctaa tagtagctgg gtattcttct gagtaggtgg 238980 tcctaaaatg ttttattttc agcttatttc ataggtataa gtcttatttt cccaaccagg 239040 ctgaaaactt ttcagaatca ggacttgtct tctc attttttatg aggggatgtg 239100 gcattattgc ttagggaatt cagatatttc tgataataaa gatgcttttc tgtttgttca 239160 ttag ggtaaaagag gaagtacaaa actatctcaa atcaagtaca ggactcttaa 239220 ttattactag ctatctaaca gctcatagaa accgataagt acct aatgccaaaa 239280 aaaagcaacc taaa aagaaaatcc aaataaaact gaaagaggca gtgggcagtg 239340 atgg gaagaaaact ttgaagtggg aaaaatctgg attcacatcc cagctttgct 239400 acttattacc tttgtgtttt aaat tatctaactt tcctgaagtt aagtttcctt 239460 ctctgtaaaa ttat aataatatat acagcatact ccacagaaga gttgtgaaga 239520 tggaatgaga aagcaaatgg caaaaactta gcacaaagta ggagctcaat caatcatggt 239580 taaaaagaac ttttatccat tgttattttt gcttatatac agtaagaatt atccaatgca 239640 aatgtaatca ctgc aattgagctt tataaagtga attataattc tcataccata 239700 gtggttctca tcaagggtga tttttttccc cccaggggac caat gtctagagac 239760 attttacttg tcacactgga aaagaggggg tgctactggc atctagtagg tagagagtag 239820 gaatgatgat aagcattctc taatgcacag gacagcattc cacagcaaca aatgatctga 239880 tccaaaatac caatagtgtg gaagttgaga aaccctacca taaagcctag ggagtccatt 239940 Page 160 715825 ‐ Sequence Listing.txt acttctgacc taaatttgtt ttatatttaa gagtggatgt ggattaaaag tagcttccat 240000 tttggtaggt tatgaagaga gttgtctaat ctgtgcttta gattctaatt ttgaggcata 240060 tttttaggct aaggcattgc aatatataag gctttctaag tttcagacat tttcttggag 240120 gtcaacaaat gaaggcttgg atta acccactaga gtagtgtaat aatggtggtg 240180 gttgtttatt gaagactaac caagtgccaa gtactctata ataatctgat ttatttttca 240240 gcaactgtat aagcaggtat tttgctctca ttttacacag actg gagcttagag 240300 aacttatgta acattactag caagttgcac agctgggatt caaactgaaa tccagctagc 240360 ttcaaagact gtgttctttc tgctgctgca tactacccct caag gctctgagat 240420 tagaaagcag gatgggtgtg ttttaaagga aataaggtag gaaagttttc aaatattaga 240480 aactctgcac atta ggtcaagttt cccactgagg ggcccttgag tatctatgaa 240540 ctcgatgaaa actctgagct gaag gtagaccaaa gggaaaggat tcatcaaaat 240600 ggatgttagc actatgccat tact tcac acggccaaaa ggacatacct 240660 gagactgggt aatttgtaag gaaaaagagg tttaaaaaag ttctcttcga tggccaaata 240720 ggaacagctc cggtctacag ctcccagcgt gagcgacaca gaagacgggt gatttctgca 240780 tttccatctg agctactgca ttcatctcac tagggagtgc cagacagtgg gcccgggaca 240840 gtgggtgcag cacactttgc cgaa gcagggtgag gcattgcctc actcaggaag 240900 cgcaagggga cagggagttc cctttccgag tcaaagaaag caga tggcacctgg 240960 aaaatcgggt cactcccacc ctaatactgc gcttttctga cgggcttaaa cgca 241020 ccaggagatt atatcccgca tcgg agggtcctac gcccacggag tctcgctgat 241080 tgctagcaca tgag atcaaactgc aaggtggcag caaggctggg ggaggggcgc 241140 caggcattgc ccaggtttgc ttaggtaaac aaagcaggcg ggaatctcga actgggtgga 241200 gcccacaaca gctcaaggag gcctgcctgc ctctgtagac tccacctctg ggggcagggt 241260 aaac aaaaagacag cagtaacctc tgcagactta aatgtccctg tctgacagct 241320 ttgaagagag cagtggttct cccagcatgc agctggagat ctgagaacag gcagactgcc 241380 tcctcaagtg ggtccctgac ccctgacccc tgagcagcct aactgggaga cacccctcag 241440 taggggcaga ctgacacctc ccag gtactcctct gagacaaaac ttccagagga 241500 Page 161 715825 ‐ Sequence Listing.txt acgatcaggc agcagcattc aaggttcatg aaaatccgct gttctgcagc caccgctgct 241560 ggtacccagg aaaacagggt ctggagtgga cctctagcaa actccaacag acctgcagct 241620 cctg agaa ctaa caaacagaaa ggacatccac accaaaaacc 241680 catctgtaca tcaccatcat ccaa aagtagataa aaccacaaag atggggaaaa 241740 aacagagcag aaaaactgga aactctgaaa gcac ctctcctcct ccaaaggaac 241800 gcagttcctc accagcaacg gaacaaagct ggacggagaa tgactttgac gagctgagag 241860 aagacttcag acgatcaaat tactccgagc tacaggagga aattgaaacc aaaggcaaag 241920 aagttgaaaa aaaa aatttagaag aatgtataac tagaataacc aatacagaga 241980 agtgcttaaa ggagctgatg gagctgaaaa ccaaggctca acat gaagaatgca 242040 gaagcctcag gagccgatgc ctgg tagaaatggt atcagtgatg gaatatgaaa 242100 tgaatgaaat agaa gggaagttta gagaaaaaag aataaaaaga aacaaagcct 242160 ccaagaaata tgggactatg tgaaaagacc aaatctatgt ctgattggtg tacctgaaat 242220 ggag aatggaacca agttggaaaa cactctgcag gatattatcc aggagaactt 242280 ccccaatcta gcaaggcagg ccaacattca gattcaggaa atacaaagaa aaag 242340 atattcctcg agaagagcag ctccaagaca cataattgtc agattcacca aagttgaaac 242400 gaaggaaaaa atgttcaggg cagccagaga gaaaggtcgg gttacccaga aagggaagcc 242460 catcagtcta acagctaatc tcttggcaga aactctacaa gccagaagag agtgggggcc 242520 aatattcaac attcttaaag aaaagaattt tcaacccaga atttcatatc cagccaaact 242580 aagcttcata agtgaagggg aaataaaata ctttacagac aagcaaatgc tgagagattt 242640 tgtcaccacc aggcctgccc tacaagagct ggaa gcactaaaca tggaaaggaa 242700 caacaggtac cagccactgc aaaatcatgc caaattgtaa agaccatcaa ggctaggaag 242760 aaactgcatc aactaacgag taaaataacc agctaacatc ataatgacag gatcaaattc 242820 acacataaca atattaactt taaatgtaaa tggactaaat gctccaatta aaagacacag 242880 actggcaaat aaga gtcaagaacc atcagtgtgc tgtattcagg aaacccatct 242940 cacgtgcaga gacacacaca ggctcaaaac aaaaggatgg aggaagatct accaagcaaa 243000 acaa aaaaagtcag gggttgcaat cctcgtctct gataaaacag actttaaacc 243060 Page 162 715825 ‐ Sequence g.txt aacaaagatc aaaagagaca aagaaggcca ttacataatg gtaaagggat caattcaaca 243120 gcta actatcctaa atatatatgc acccaataca ggagcatcca gattcataaa 243180 gcaagtcctg agtgacctac actt agactcccac acaataataa actt 243240 taacagccca ctgtcaacat gatc aacgggacag aaagttaaca aggataccca 243300 ggaattgaac tcagctctgc accaagcgga agac atctacagaa ctctccatca 243360 caaatcaaca gaatatacat cagc accacaccac acctattcca aaattgacca 243420 cgtggttcga agcaaagctc tcctcagcaa aaaa acagaaatta taacaaactg 243480 tctctcagac cacagtgcaa tcaaactaga actcaggatt ccca ctcaaaacca 243540 ctcaactaca tggaaactga acaacctggt cctgaatgac tactgggtac ataacaaaat 243600 gaaggcagaa ataaagatgt tctttgaaac caacaagaac aaagacacaa cataccagaa 243660 ggac gcattcaaag cagtgtgtag agggaaattt atagcactaa atgcccacaa 243720 gagaaagcag gaaagatcca aaattgacac cctaacatca caattaaaag aactagaaaa 243780 gcaagagcaa acacattcaa aagctaggag aaggcaagaa ataactaaga tcagagcaga 243840 actgaaggaa atagagacac aaaaaaccct tcaaataatt aatgaatcca ggagctggtt 243900 tttggaaagg atcaacaaaa ttgatagacc actagcaaga ctaataaaga agaaaagaga 243960 gtagaaaaat aaaaaatgat aaagaggata tcaccactga tcccacagaa atgcaaacta 244020 ccatcagaga caaa cacctctaca aact agaaaatcta gaagaaatgg 244080 ataaattcct atac accctcccaa gactaaacca ggaagagttg aatctctgaa 244140 tagaccaata acaggctctg aaattgtggc tataatcaat agcttaccaa ccaaaaagag 244200 tccaggccca gatggattca cagccgaatt ctaccagagg tacaaggagg aactggtacc 244260 attccttctg aaaccattcc aatcaataga aaaagaagga atcctctcta actcatttta 244320 tgaggccagc atcatcctga taccaaagcc tggcagagac acaaccaaaa aagagaattt 244380 aata tccttgatga acattgatgc aaaaatcctc agtaaaatac tagcaaaccg 244440 aatccagcag aaaa agcttatcca ccatgatcaa gtgggcttca tccctgggat 244500 gcaaggctgg ttcaatattt gcaaatcaat aaatgtaatc cagcatataa acagaaccaa 244560 agacaaaaac cacatgatta tctcaataga tgcagaaaag ttctttgaca aaattcaaca 244620 Page 163 715825 ‐ Sequence Listing.txt acacttcatg ctaaaaactc tcaataaatt aggtattgat gggacatatc tcaaaataat 244680 aagagctata aaac ccacagccaa tatcatactg aatgggcaaa aactggaagc 244740 attccctttg ggca caagacaggg atgacctctc tcaccactcc tattcaacat 244800 ggaa gttctggcca gggcaattac gcaggagaag gaaataaaga gtattcaatt 244860 aggaaaagag gaagtcaact tgtccctgtt tgcagatgac atgattgtat aaaa 244920 ccccattgtc tcagcccaaa atctccttaa gctgataaac aacttcagca cagg 244980 aatc aatgtgcaaa aatcacaagc attcttatac accaataaca gacaaacaga 245040 tcat gagtgaactc ccattcacaa ttgcttcaaa gagaataaaa taactaggaa 245100 tccaacttac aagggacatg aaggacctct tcaaggagaa ctacaaacca ctgctcaatg 245160 aaataaaaga ggatacaaag aaatggaaga acattccatg ctcatggata ggaagaatca 245220 atattgtgaa aatggccata ctgtccaagg taatttatag attcaatgcc atccccatca 245280 agctaccaat gactttcttc ttgg aaaaaactac cttaaagttc atatggaacc 245340 aaaaaagagc ctgcatcgcc aagtcaatcc taagccaaaa gagcaaagct ggaggcatca 245400 cactacctga cttcaaacaa tactacaagg ctacagtaac caaaacagca tggtactggt 245460 accaaagcag agatatagat caatggaaca gaacagagcc ctcagaaata acactgcatg 245520 tctacaacta tctgatcttt gacaaacctg agaaaaacaa gcaatgggaa aaggattccc 245580 tatttaataa atggtgctgg gaaaactggc tagccatatg tagaaagctg gatc 245640 ccttccttac accttataca aaaattaatt caagatggag ctta aatgttagac 245700 ctaaaaccat aaaaacccta gaagaaaacc ttat cattcaggac ataggcatgg 245760 gcaaggactt catgtctaaa acaccaaaag caatggcaac aaaagcaaaa attgacaaat 245820 ggggtctaat taaactaaag tgca cagcaaaaga aactaccatc agagtgaaca 245880 ggcagcctac aaaatgggag aaaattttcg caacctactc atctgacaaa gggataatat 245940 ccagaatcta caatgaactc aaacaaatct acaggaaaaa caac aaaa 246000 caaa ggacatgaac agacacttct caaaagaaga catttatgca gccaaaaaac 246060 acatgaaaaa atgctcacca tcactggcta tcagagaaat gcaaatcaaa accacaatga 246120 gataccatct cacaccagtt gttagaatgg cgatcattaa aaagtcagga aacaacaggt 246180 Page 164 715825 ‐ Sequence Listing.txt gctggatagg atgtggagaa ataggaacac ttttacactg ttggtgggac tgtaaactag 246240 ttcaaccatt gtggaagtca gtgtggcgat tcctcaggga tctagaacta gaaataccat 246300 ttgacccagc catcccatta ctgggtatat acccaaatga ctgtaaatca tgctgctata 246360 catg cacactatgt ttattgcggc caca atagcaaaga cttggaacca 246420 acccgaatgt ccaacaatga tagactggat taagaaaatg tggcacatat acaccacgga 246480 tgca gccataaaaa gttc atgtcctttg tagggacatg gatgaaattg 246540 gaaatcatca ttctgagtaa actatcgcaa gaacaaaaaa ccaaacaccg catattctca 246600 ctcataggtg ggaattgaac aatgagaaca catggacaca ggaaggggaa catcacactc 246660 tggggactgt tgtgggggtg gaggaggggg aagggatagc tttaggagat atacctaatg 246720 ctaaatgacg agttaatggg tgcagcacac gcca catgtataca catgtgacta 246780 acctgcacat tgtgcacatg gaaa cttaaagtat aataataata aaagaaaaaa 246840 aaagaaaaag aggtttaatg gactcacagt tccacatggc tggtgaggcc tcacagtcat 246900 ggtagagggt gaatgaggag caaaagcatg tcttgcatgg cggcagaaaa gaaagcatgt 246960 gcaggggaac tgccctttat aaaaccatca gatctcatga gacttattca ctgtcatgag 247020 aacagcacaa gaaaaacctg cccccatgat tcaattacct tccaccagct ccctctcatg 247080 acacatgcgg attatgggag gtgcaattca agatgtgatt tgtatgggga cacagccaaa 247140 cacc taca atttgccgat tcagcaacag ttttcaggtc ttctattttt 247200 aagcctaatg caatatattt tatgaattct tcctatttat gtttttcctt ttaaataagt 247260 tctactatct taactatcac tttcaaatat aatgcaagct acatatgcca ttttaaattt 247320 tttagtagtt aaaa tgaa attaatttta acaaagtagg ttatttatcc 247380 caatatatcc aaactattat gaca tgtagtgaag ctaataaaag cattcattgt 247440 taatgatcta tctcttacat tattttttcc taataaatct tcagaatctg ggtgtgcatt 247500 ttaactttcc agcacatctc aactgggatg tgaaattttc agcaattaaa gtgaaatata 247560 gccctatcaa aactattaat gttgcattta ggaaaaagat cact ctttttattt 247620 ttaaatttga gtttaaatta attaaaatgg aataaaattt aaaattcaat tctctgtcac 247680 caca tttcaagtgc ccta accc atggctacca tattggacag 247740 Page 165 715825 ‐ Sequence Listing.txt cacagatcta tatt gctcagaatg tggtccccag agcagaatca acagcatctg 247800 tgaacttatc aaaagtgcag tatttcagtt cacacctact gaatctgcat tttaacacaa 247860 tccccaggtg atgcttgttc acatgaaagt tgtgtctctc gcag atcttttcaa 247920 caaagagccc agca catgaatcaa taactgtgag gaataaggaa caca 247980 ggagaatggt gccagggttg gcattaatga tgtgctctgg tgaaaagtcg taggtttccc 248040 acaaaggcaa ccatggctat tctattgttt gaactgacac agagccattc tagagcttgg 248100 agttggctct gctcccagaa tctacatcaa agaatctaac actaacttcc atgactacca 248160 caattaaggc agctgcacac cccaccacta tatatatttg aaattgcaac tttagaaccc 248220 ctgtaacaca gccgtgagca tgtttctgct atacacaagt taag gtcgaacctc 248280 cctgggagac cccaggaaga tcacccacaa gagtggcttt tgttgtctgc ctcactgtca 248340 gaga acag tcaa ctta tatggaggtt ggcccagatg 248400 cccctgggga ttcaatgtat tctgcttcac ctcactaatc cttatttggt ttgtttttca 248460 cagaactcag tatttgatgg gcctttcaat attttccttt aaggaattca ttgtactaat 248520 ataacataga agctcattgt tctaataagt ggtccccaat gttggctgca cattagaatc 248580 acctggggca ttttgaaaaa taccaatgcc caggcatcac cccaatctaa taaa 248640 gaag tgtt aaagatcccc aagtgattac cagc cagagttgaa 248700 atccactggt ccaattagaa ggaggcctta gctagcggtc aggtgcccaa ggaaaggcat 248760 ctcaagtttt aatgcgcata cagatagctt gggatttgtt aaaatgcaga ttctgatcca 248820 gtaggtatgg gtggaaataa acccatgttt gtgtacagat gtttctcttg tggtatgtgg 248880 ttggtaatca tcctcagtat gtttccattt ccggcaaact gggttgagtt gatgacccta 248940 ttcttactcc tccctgaaac ctttgtctct ggct cccagttctc attaatcact 249000 actttctgtg atattctgaa gcaattatta tctttaactg ccttttttca ttagctactt 249060 ctctatctgc ttatgtacgt gagttatttc ctctactgga ttacgatctt caaggtagat 249120 ccaaatatca tgtcattttt ataattctca ctgcacctaa agagtgcctt acacacaaat 249180 gccacttgtt gattaattga aacagggaat agctgatgtg atcatctcaa aaaatatcca 249240 aaagacttaa aaatgcaaga tatttttctt tgttggacag aaaaagaaag tttagatagg 249300 Page 166 715825 ‐ Sequence g.txt caagggggta ggagatattg aggctttcaa tttttatttc actcggtaca tatttaaatt 249360 ttgaagaatt attttgtaat ttagtgattt tttg ttgggaatag ggcactattg 249420 acattttgga ctagatcatt ctttgttgtg gctgtcatcc tgtgcattgt aatatgtttc 249480 acagcatccc tggcctcaac ccactagatg ccagtatcac cctttacccc agtcttgaga 249540 aatg tctccagtca ttgcaaaatg tctcctggga aactcattca tggttgagaa 249600 cccttagttt agaaaaatgg aagtgtgaca cagctgtctt accgcactaa tatagacctg 249660 aaaaaaataa aaaattaaaa acatgcacat aagagaatga caagctatgt tctgagcaat 249720 atgtgtatat ataaatatta atataaaaat gttctctgtt cctgcgtttt ggaggccatg 249780 taga ccatatttat ctttgtattt gtcatcttgg tcattctctt tataaaaata 249840 gaggtatatt gcatgccaat gctcctcagc ttatgaggtt acatcccaat aagcctgttg 249900 taaatttaaa aaatcataag ttagaaatgt caaaacttga attt aataccctga 249960 taaacacatc ataaagttga aaaatcctaa ccat catgagtcag gaactatttg 250020 tatatgaaac atttttaaaa tctgaacata ggaa tatg tagtggtagt 250080 aattccacca agcaagagaa tacatagagc catt aagaaacagt gactgagatg 250140 attctcattc tcaggaaact ggtccagccc ctttacataa aatattctgt tcagtgtgct 250200 gtgatccttg gactgaatat actgttttag caagcagagt tgttaagcta aagcctgcac 250260 atcaacaggt gttcaatgtc tgctgaataa atgaagaatg aatgaatatt aactgcacct 250320 ctaaacccta aaaa gctttaatgt gctcatcaca aaagacccta ttttgttgca 250380 tttgaaattt caagcttcaa aaatgaaatt acatgcaaaa gtatattatc atcaatgaga 250440 ataaatggcc tcaacaaaat tacaagatag aaaacaaagt ttcatttgtc agttggtttc 250500 ttctggcaat agaaggctcc actt cattagcttc agatatttca gtgacagaaa 250560 tttaatgttg gcaaagcatt gctatacttt caggcttgga ttggaatgcc ttac 250620 tttttcctac cattcctggc taaaaacttg aatgtgagaa acaa agtg 250680 gtagcaagca gaatgtctcc taagctccaa ggggaaaaaa tgatataagt cagtggttcc 250740 caaattaacc atcaaatgct acccattaaa atcactgggg aacttttaaa aattaaatgc 250800 ccaactaaca acaaactgta tgaaaaagaa atttagaaaa caatcctatt tttaaaagca 250860 Page 167 715825 ‐ Sequence g.txt gcaaaaaagt aaaatactta ggagtaaatt taaccaagga agggaaatat ctgtttactg 250920 aaaactatga aatgttgatg attg aagatggtaa aaataaatga aaagataaat 250980 atgtatggat tggaagaatt aatattgtta agagatctat actacccaaa gcaatctata 251040 gattcaatgc aatcctatca aaattccaaa gtcattcttt atagcagtag aaaaaaatca 251100 taaaattcat atggaaccac aaaagactct gaatagccaa agcaatcttg aaga 251160 gcaatgctgg caca ttatcagatt tcaaaatata ttacaaagct acaatattca 251220 aaatagcatg ctactggcat taaaacagat ctatcaacta ctgaaacaga atagtgagcc 251280 cagaaataaa cccacacatc tatgatcaat tgattttcaa caaagatacc aagaacacac 251340 aatggggaaa gtct tcaataaatg gtgctgagaa aactggaaat ccacatgctg 251400 aagaatgaaa cctt tccc ttatacaaga atcaactcaa aatagattaa 251460 agacttaaac ataagccctg aaactataaa actaatgcag aaaatatagg gggaaatcta 251520 catgatatta atctaggcag aagtttcatg gatatgacct caaaagcaca gacaacaaaa 251580 gcaaaaatag acaaatggca ttgcatcaga ctaaaaaact tctgtacagc agatgaagca 251640 agag tgaagagaca acctacagat taggagaaaa tatttgcaaa tcatatatta 251700 gataaggggt taatattcca aaaggtacaa ggaaatcaaa ctactcaata acaagaaagc 251760 caattaccct attaaaatat agca ttgggagata cacctaatgc tagatgacga 251820 gttagtgggt gcagtgcacc agcatggcac atgtatacat atgtaactaa cctgcacaag 251880 gtgcacatgt accctaaaac ttaaagtata ataataattt tttttaaaaa aaagcaaaaa 251940 ttaaaaaaaa aaaaaaaata tata tataggcaac aaacttaaat agacatttct 252000 caaaagaagc aagtatcacc ctgatttaaa acctggcaaa gacacaatga gaaaacaaac 252060 tacaggccaa catctctgat gaacatagac acaaaaatcc ttgacaaaat actagcaaac 252120 tgaatacagc agcacatcaa aaagttaatt tgccatgata aactagtgtg ttagggtgtt 252180 tgct attaaaaaat acccaagact ttta acaa aggcttaatt 252240 tgttcatggt tctgcagcct gtacaagcat ggtgccagca cctggccagc ggaa 252300 gcctcatgaa atttttattc atggcagaag gtgaaacagg aacaggcaca tcacacaggg 252360 gaagcaggag taagagagag tgtgagggag gtgccacaca cttaaacaat caggtctcac 252420 Page 168 715825 ‐ Sequence Listing.txt aagtactcac ctgc aaggacagca ccaagccata agggcccacc cccatgattc 252480 ctcc caccaagacc cacctccaac attgggcatt atatgtcaac atgagatttg 252540 taca aatattcaaa ctatatcaag taggcttcct tcttgggatt caaggttggt 252600 tcaacataca cagatcaata aatctgactc accacataaa cagaattata aacaaaaacc 252660 acatgatttc aataggtgtg ggaaaagctt ttgataaaat ccaacctccc ttcatgttaa 252720 aaaaaaaaaa aaaaacctta agaaactagg cggccgggcg cggtggctca cacctgtaat 252780 actt tgggaggccg aggtgggcgg atcacgaggt caggagatcg agaccatccc 252840 ggctaaaacg gtgaaaccca acta aaaatacaaa gccg ggcgtagggg 252900 cgggcgcctg tagtcccagc tacttgggag gctgaggcag gagaatggcg tgaacccggg 252960 aggcggagct tgcagtgagc cgagatcccg ccactgcact ccagcctggg agca 253020 agactccgtc tcaaaaaaaa aaaaaaaaag aaactaggca ttgaaggaat atttctcaaa 253080 atagtaagag ccatctgtga caaacccaca acaacataat aataaatggg caaaaactgg 253140 aagcgttccc cttgaagaca ggat gccttttctc acctgttgta ttcatgacag 253200 tacttgaagt gctagccaga gcaatcaggt aaaagaaaga aataaaagac atcaaaatag 253260 aaaaagaaga aatcaaacta cctctcttta ctgactatat aattctatgc aaac 253320 ctaaaggctc aaaa ggaa ctgataaaca acttcagtaa agtttctgga 253380 tacaaaatca atgtgcaaaa atcagtagca tttctataca gcaatagtgt tcacattgag 253440 agccaaacca agaatgtaat cccatttaca gtagccacaa taaa gtacaactag 253500 ggatacatct aaccaaggag atgaaagatc tcataatgct gcacaagtac agccatttaa 253560 tcttcaacaa agatgacaaa attagcaatg gggaaaggac tctctagtca gtaaatggta 253620 ctgggataaa tgtaaatgtc tggc tagtcagtaa gtgatactga ctagctatat 253680 gtagaagaat gaaactggac ccctaccttt caccatatac aaaaattaac tcaggatgga 253740 ttaattattc aaatgtaata tctcaaacta taagaatgta atattcaaat atatctcaaa 253800 tgatatacaa actataagat atatattata tctcaagcta tatacaaact ataagaatgt 253860 aatattcaaa tgtaatatct caaactataa gaatcctata ccta ggaaacacca 253920 ttctggacat cagccttgga aaagaattta tgactgagtt ctcaaaagca atttcaacaa 253980 Page 169 715825 ‐ Sequence Listing.txt aaacaaaaac tgacaagttt ttctgtgtag aagctcttag aaaa agaaaccagc 254040 gtaa acagcctaca gaatgggtga aaatcttcac aaactgtgct tccaaccaag 254100 tatc tggcgtctgt taggaactta aacaattgag caaacaaaaa acaaccccat 254160 ttaaaaatgg agca gaca gttctcaaaa gaaggcatat aaacagctaa 254220 caaacatgaa aaaatgtctc acatcactaa tcatcagaga aatgcaaatc acaa 254280 taatatgcta tatcacacca gtcagaatag ctattatcaa aaagtcaaaa acaacagacg 254340 ctggcaaggc tgcagaaaaa aaagtgaacg ctcatacacg gttgctggga atgtaagtta 254400 gttcagccac tgtgaaaagc agtttggaga tttctcaaag aacttgaaac agagttacca 254460 ttcaacccag caatcccact gggtatatat ccaaaagaaa gtacattgtt tcttttggat 254520 attgttctac ccaaaagaca catacactca catgttcatt acaacactgt tcgcaatagc 254580 aaagacatgg aatcaaccta ggtgcccaac aaaggtggat tggattaaaa aatgtggtac 254640 atgtccacca tgggatacta aata aatg aaatcatgtc ctttgcagca 254700 acatggatgc agctggaggc cattatacta agtgaggtaa tacaggaaca gaaaaccaaa 254760 tactgcatgt ttttacttat aagtgggagc taaacattgg atgg atataaaggt 254820 ggcaacaata gaaactgggg actaacagag tagggaggta gggagcagag agaggactaa 254880 aaaactatta ggtactatgc cctg ggtgatggga tcaatcatac cccaaacctc 254940 agcatcgtgt ccca ggtaacaaac attt gttccctgaa tctaaaataa 255000 aagttgaaat tacaattttt aaaaggatag aaactagtca tcagcgtgtt ttttaatttt 255060 ccaggtgact ctaacattca ataattattt taaataatta tttctgtctg tagaccttct 255120 gccagctact aagtttcagg aattttgatg gtctcattaa agagaacctg acaaccccac 255180 ttacaagtgc ttcagctaag ttat aatattttca tattgccaag gatccagtag 255240 tgtctttttt acagtgagtt acaaattcct gtttttgtga cagtgacagg ccaaaattaa 255300 gtga tttttaaact gaaaaagtga ctgtccaata gaggctaaaa agaaaactaa 255360 aattatattt tgtcaatttt agtgttaagt gtgatttttt gctttgtatg atag 255420 tttttttatt gagataaaac ccaaatagca taaaatccac ctttttaatc tcaaagtggt 255480 ttttggtata ttcacaatgt tgtgcaacaa tcactactat ctaactctag aacattttca 255540 Page 170 715825 ‐ Sequence g.txt ttacttcctc atggaaccct gtacccatta gtagtcactc ccagtttccc attcacctca 255600 tttcctggca accactaatc tacttttctg tctctctgta tgtgactatt attt 255660 catgtaaatc agatactata atatgtggcc gtct gacttctatc acatagcaac 255720 atattttcaa ggtcattcgt gttgtagcat gtatcagtat tttattcctt acaa 255780 tactttatta tata ccacatcttt tttatccact catcagttga tggacctttg 255840 agttgtttct acttttctgt tattttaaat aatgctgtta tgagcattct tgcacatgtt 255900 tttgtgtgat catatgtgtt tgcttctctg ggcatatacc taggagcaga attgcagggt 255960 catatggtaa ctctgtattt aacattttga ggaaccccca aattgctttc cccagtagct 256020 ataccatttt acattctgaa cagaagtgtg tgagggtttc tattacttca catcctcttg 256080 ctttctattt taattattta attatttaat ttaattatct aagatgcctt ttaccctaac 256140 caaccagaaa ataaacttga ctgaatttag tgctaattgt ttttgcatag tcattcagta 256200 taattgtctt tgacatctca aaacactgct tatgcagaat tttt aaaacagtga 256260 aatcatagca attctatttc ctaagtcagt tcttcttcag ggtagtaagt tataggtctt 256320 tgaggtcatg ttcctgtttc catcttccaa aaggcaacat tattaaaatc ctgt 256380 cttg gcatatcccc ctctctatcc agagaaaaga tcactgacag aatagtgtcc 256440 ccacctttct atcttagagg tctcattacg agtcagtatg cttttaaaag aattaatgga 256500 taaagagcta gacatcaaga agaagagaga aaattttaaa taagacagag gagtgtatga 256560 tcactctttc gatt aaatgaaata aagg caataaacta actgcaccaa 256620 gtaaatcttg tgaaagcgaa aggaaagagg agaaggaaga tttgagtgct gaaaaccagg 256680 ataaattgta ttcaaccacc agcattaagg gaagttatac aatacatttt atgaagaaag 256740 tgttccatga aaataaaaca acaaaaagaa agtttggtga aggtttaaat tgcc 256800 aatagtagta tatgtgcaat tatctactga cactgctata caaatgagct atctatatag 256860 gctgtgacca cataacctca cctgccaaac cacagtacta taaataaata cttttcccag 256920 caga gctcagttga cttgagattc tggt aactggaaat gtagactgtg 256980 cctttatttg tcct acaattttct ttaatgtacc agcaattcat tatttaaagt 257040 ttactagagt ttaatttaaa aaaa aggaagaaat tggctgggta tggtggctca 257100 Page 171 715825 ‐ Sequence Listing.txt cgcctgtaat cccagcactt tgggaggcca aggcgggaag atcatgaggt caggagatcg 257160 agaccctcct aatg gtgaaaccca acta aaaatacaaa aattacctgg 257220 gcatggtggc acacgcctgt agtcccagct actcaggagg ctgaggcagg agaatcgctt 257280 gaacctggga ggcggaggtt gcagtgagcc aagatctcac cactgcactc caacttggtg 257340 acagagcgag actccatata aaaaaaaaag gaagaaatta atagttcagg tgagaacttg 257400 tgaattttta ttctcaactc taagctagta agtgcttaaa tagaagactt gagc 257460 tgtaccttct taattctaca gagaatcatg aggaaaatca aatataaatg tgaatttctt 257520 atgttcagta ttgtccaaaa agaaaatatt ttattaaatt ttttgtcagt tgccatcatt 257580 atttaaagcc ccag tagcctatac tatttttgga atggagtgtt tgcagtttca 257640 taaccacttg ataacaccat aggttaaaaa aaaagtctac cagtcttttt cagatggcct 257700 ctttgacaat gcattattta tagggaagtt cagttacttt taaa gacaagccaa 257760 aagaaattac agatctcttt taccatattt tgatatacta gcagcatcca ctcaggacag 257820 gacctttatt aaaagggggc ttaaggtact tttaattgga ggaattactg aattcctgaa 257880 gctcttcaaa agca cttgggatat gacaagagta ctttggagaa ttgg 257940 tcccaaagca gagattcaag aggaggactc cagctagctg ggtaaggggt tccttcctct 258000 caacctaagt gtttatgtaa gcctgctggg ggccaggaac tgcgtaaaac tcagtaagct 258060 cagtacttct cagcacagaa tccagtccca aggaagcacc cagcaaaaat ttaggttgaa 258120 ttttctttaa aataaaataa agaaaaaagt aaaattaaaa aaaaaataca attcaactac 258180 tcagcccatt ccattccggg tagttttggc tcagaatgct ggaagagttg gataggctat 258240 tagtgagaga actcaaaact ccccaaactc cacttcatta cttt atattttttc 258300 tgaaaagagt attgccaata tatcaataaa gctttttgct atgacttcag agtgcccagg 258360 tcactaggga aaagtatcaa tcct gaatccacaa tgag agccagccac 258420 tctg cgtgagtgtg ctct acccttacga gtgtcatcac agaattgcag 258480 cattctcttt tcattgtttc tcaggaaaac atagacaaag gctctgcttg gattttttta 258540 atttaacact aatatgtaat aatatagcaa catctcctag ttatctagaa ctcaggcttt 258600 gatagctgtg actgtctaga ccac agaaaatcac ctctgaacag tgagggaaat 258660 Page 172 715825 ‐ Sequence Listing.txt agctgccaca gtatcaccac ctactccaag cctc tcaacccgca accaacagac 258720 tagt tcagtacagc tttgaatgca gcccaagaca aactcgtaaa ccttcttaaa 258780 acattatgaa atttttttgc ttca tcagctatcg ttagtgttag tttt 258840 gtgttgctca agacaagtct cttcttccag tgtagcccag gaaagccaaa agattggaca 258900 cctatacttt ggatgtttca accg atatacttat aattacatgt ttcaactagt 258960 actaatgaac ttac aaat ttcaaattag caatgttcat catttgctct 259020 gtaa caacagttaa atag gttgacaatc acaactgatt gtgaggatgg 259080 aaataataac aatgagcatt tatataatgc ttactctata ccaggcactt ttctaagaac 259140 tttacataga ttagctcact taatctttac aataaccctg tgacatacca ttattatccc 259200 acag gtgaggaaac tgaagaagtt aagtaatttg cccaagatta cagattgtat 259260 gtgattgagg taggatttga actcagcagt ctggcaccaa aatcagcact ctcagcctct 259320 tatt atcaaaagta atttcctggt agcttctttc aattgtcatg gcaactctca 259380 agataaagaa ttattgtttt taataaataa tgtcattccc agaaatgaat tatgtgtgaa 259440 tcatactaag ctgcagtgag agaatgaata tcaccatcac agtggtgaat ctacttagtg 259500 taggggtaaa aggccagtct ctcccagcag ccctgcacat aggtacaccg taattcacta 259560 ggataatccc tgatcgccat gctgtcataa aaaaacgtta aatgatgttt aacaggtttc 259620 attaatgatt cagagaatct tataatatgt cttaggaaaa ataatttcag gagtaacttt 259680 cagttagcta gacaatacag ttctgttgag catctcataa tctatgccag acaaaggaaa 259740 cattcttgcc tttctttgag ggaattatag accaacaatt ttattaattt ttca 259800 tcgaggcaag attagcttca tgaacaatgt ttctcaaact gaaagtagtg acctgtatta 259860 gtaaatcaat ttatagggtt gcaagcagca tcatttataa actgaaatca gaattcattg 259920 caggcagtaa ttttgagaca ttttatttta catgtgcgtg tcta tcatataaat 259980 aagtatgtga gaacatttta aaacatttaa aatatattta tatatctaaa gtttaaatgt 260040 aaatatatat ttatattaat aatataatta atatgaatta tatt aattcatatt 260100 aacttatatt aatttatatt aacaatatgt aaacaatata ttaattagta atatattata 260160 ctaatattag tatgtattaa tatattatta taatatatta tatattaatt aatatattat 260220 Page 173 715825 ‐ ce Listing.txt tata ttatatatta attaatatat tatatattgt atattatata ttaataacat 260280 actattatta atattttaaa tatattttaa tatacttaaa tttatactta aaatttacat 260340 ataa ataattttcc tcac tttcaaaaac tttgaaagcc accagtgcag 260400 tggttaagaa tacaaatttt gggctgggca tggtggctca taat cccaacactt 260460 tgggaggccg aggtgggtgg aggt caagagattg agaccatcct ggccaacatg 260520 gtgaaacatt gtctctacta aaaatataaa aattagctgg gcacggtggc acgcacctgt 260580 agtcccagct atgcaggagg ctgaggcagg agaatcactt gaacccagga ggtggaggtt 260640 gcagtgagcc gagatcatgg attc cagcctggcg acagagcgag actgcatctc 260700 aaaaaaaaaa aaagaataca aattctgaag cacagctgtt gagttggaat catggctgtg 260760 ccacttaata accaagtgac tttgggccag ttattttact tctctatgcc tcagtgtcat 260820 ctattcagta gtgagaataa tagtacctaa ctcattctag ttttgagaat gaacactttt 260880 acat ataaaatgtg taggacagag accccaaaga agccgtagtt atat 260940 tgttattctg ttcctgctta agaaggggac ttggaaaaat aatgatgttg aatgcagtaa 261000 cttctttcac tcatggaaga attacatatt cacatcttct ttgctcatca aacctttgaa 261060 gatcatgcat gtctcattct gtaacatcgc cttaaccaaa tataaaggct aaatacaaag 261120 gtgtttttaa ataactgata catttaggcc agtcacacaa agattttacc caaagcctat 261180 atag tccaagaagt agacttgttc tactgcaatc tctt gtttattatt 261240 tgtgaaagga acattatggt ttcaccacag ttggcctggc caacgtgctt atgcagtcct 261300 cagaacatat gaaagtgatt tcggctgaca attt tttg gcttatgttc 261360 aataatagcc attctttatc cagatcaggg tgactgagca tgctgtaacc attcttctct 261420 tctaaaactg acccttgttt gactgcatat gcagattgct tagcagaacc catatccacc 261480 ataacgggcc aaaagtcatt aatg tgcttttctt tttttttctt ttttttttaa 261540 ttccatgaaa taag ataaattaat tataaacatt gcaaaacact ttttttttta 261600 gacagagtct cactatgtca cccaggctgg ggtgcagtga cacgatctca gctcactgca 261660 acttccgact cccaggttca agtgattctt gtgcctcagc ctctctgagt agctgggatt 261720 acaggtatgc cccaccagac ctggctaatt tttgtatttt tagtagagac ggagtttcac 261780 Page 174 715825 ‐ Sequence Listing.txt tatgttggac gcct cgaactcctg ggta atccacccgc ctcagcctcc 261840 caaagtgctg gaattacagg tgtgagccac tgctcccagc catg attttttgat 261900 tgaatgctta atgtctttct attattatta ttttttttta tttg ttctggcatg 261960 caca acgtgcagat ttgttacata ggcatacatg tgccatgttg gtttgctgca 262020 cccattaaaa attaattcaa gatggattaa agacttaaat gttaggccta aaaccataaa 262080 agaa gaaaacctag gcaataccat tcaggaaata ggcatgggca aagacttcat 262140 gactaaaaca ccaaaaacaa tggcaacaaa agccaaaatt ggcaaatggg atctaattaa 262200 actaaagagc ttctgcacag caaaagaaac taccagcaga gtgaacaggc aacctacaga 262260 atgggagaaa atttttgcaa tccgcccatc tgacaaaggg ctaatatcca gaatctacaa 262320 agaacttcaa taaatttaca agaaaaaaaa aaaaccatca aaaagtgggc aaaggatata 262380 aacagacact tctcaaaaga agacatttat gcagccaaca gacacatgaa aaaatgctca 262440 tcatcactgg tcatcagaga aatgcaaatc aaaaccacaa tgagatacca tttcacacca 262500 gttagaatgg cgatcgttaa aaagtcagga aacaacagat gctggagagg atgtggagaa 262560 ataggaacgc ttttacactg ttggtgggag tgtaaattag ttcaaccatt gtggaagaca 262620 caat tcctcaagga tctagaacta gaaataccat atgacccagt gatcccatta 262680 ctgggtatat agga ttataaatca tgctactata aatacacatg cggccgggcg 262740 tggtggctca tgcctgtaat cccagcactt tgggaggctg aggcaggcag atcacaagtt 262800 caggagatcg agaccatcct ggctaacatg gtgaaacccc atctctacta aaaatacaaa 262860 aaattaggca ggcgcagtgg cgggcgcctg tagtcccagc tactcgggag gctgaggcag 262920 gagaatggca tgaacccggg aggcggagct tgcagtgagc cgagatagcg cagt 262980 ccagcctggg caaaagggca agactccgtc tcaaaaaaaa aaaaaaaaaa atat 263040 gtac gtttactgca gcactattca caatagcaaa gacttggaac aaat 263100 gtccatcagt gatagactgg ataaagaaag tgtggcacat atacaccatg gaatactatg 263160 cagccataaa aaaggatgag ttcacgtcct ttgcagggac atggatgaag acca 263220 tcattctcag caaacgatca caagagcaga aaaccaaaca gtgt gttccaactt 263280 aactcattgt tcttagtgat ctta ggggcaaagt taggctctct tgttaattgc 263340 Page 175 715825 ‐ Sequence Listing.txt aacattcctt tcagaggtgc tataaatgga tgttgaacta tttt agatttaatc 263400 tttaaaaatc ataagaaagc aagaaatatt actagttcag aaatgatttt ctgg 263460 ctaatcagag aagacctaag agtctatagt agtcatttgt cgta gtaaaagtaa 263520 gattctaata ggatttttag acatagtgag aaaggtgttc attttaagat tatggtagtt 263580 cctctcagat agcc ttaagatgac actaaggagt tggactttag gaatgctgag 263640 tgtcttcagc cacagcggca tact agatgtgaca ggatgtgatt aaggagaaac 263700 gcca ggcacaatat agttcttctt gcctccaaaa gaggagtcac ccactttctc 263760 acactcactg tgatacattc catttgctaa gaaaagtggc ttgtgtcatt cttgagcact 263820 acttttaagt tctgatatat taaattcatt tactctgtat taatagcatt caaatattta 263880 gtaaagttaa tctc acactttttc caaagtaacc caccagctgt gtcctgtgct 263940 tcaagctatc ttataagact gcaatcaaag tgtcagccag ggctgtggtc tcatctgaag 264000 gctggatagg gaaagattgg ttcccatgct tatttacatt gttgttggca ggattcagtt 264060 cctcaaaggt tttttttatt tttatatatt tttttttgag atggagtctt gctccatcac 264120 cagactggag tgcagtggcg caatcttggc tcactgcaaa ctccgcttcc caggttcaag 264180 caattctcct gcctcagcct cccaggtagc tgggattaca ggtgcatgcc accatgccca 264240 gctaattttt ctatttttag tagagatggg atttcaccat gttggtcagg tcga 264300 gacc tcatgatcca cctacctcag cctcccaaag tgctgggatt acaggcatga 264360 gccaccgcgc ccagccagtt cctcaagggt ttttatactg agggcctcta cttcttgctg 264420 agtgttggcc agaggccatg cttagttctc tgctgtatgg ccac acagcaacgt 264480 acttcatcaa aaccagcaaa agggtgagtc ttaa aaagaagtct caatcttttg 264540 taacctaatc atagaactgc catccactcc ccat attcttctga ttagaagcaa 264600 gttactcaag ggaaggaaat acataaggct gtgaatgaga gaagacagga atcattggag 264660 gctactttag gggctgtctg ccacagcact taacagcaca tacccagcca taaaatttaa 264720 aaaagccgga aagagagaag gagggtgcag ggtaaaataa agaaaagagg aaggtggaag 264780 ggaagaaagg aaga aagacattta aaaagacaag aacaaaacag ctctgctgca 264840 ctgt atcggagttc catgtgcaga cacacacgtc atcacatcag caccacaccc 264900 Page 176 715825 ‐ Sequence Listing.txt ataaatttcc tatttcttat ttacaatgag aaggtaataa ggactttcta tgcatctgga 264960 agga aacaataaat atac taagtttaag taatcaaaat gtgtttcaga 265020 ttagttattt tttcttttta agtttttttt tttgtttcag ctgacaaagt tttc 265080 tttc aagttttgaa gttgagttta ttattcttgc tattatgtaa caggcatatt 265140 ttacagagaa tataggaacc tgattgacat ttgtatttgg tgttctattg ttgtttcaat 265200 tcaaatgcca aaattatgtt tttgttgtgt acgttattgt tcataattat atatgcctct 265260 taattgtaaa agcgaagctg taaaattgta aagtactttg tgtctcatct attccaggca 265320 ttctactaag gaaatcaaga ccaaatggct tgggaaggtc aaat agtgtcagag 265380 ccagaactag agtacacatc tctcaatttc taatctagtg catttccttt tcttatttct 265440 gtgcaaacga acagttagaa atag tctcctcaga agca ttaaaacagt 265500 tgtggtttaa atatttagtt atta ctaactttgt agaaggacct aaaatagtgt 265560 ttgttttcag tgcttcaact aatagtaaaa aggaatattt tcagtgcttt actgtatgag 265620 aggtgcttgc ctaacgaaat acacatcttt ttcactgtac gtaa cagataatgt 265680 gggctcgtac acctcagtgt tctgagaggg gttggtaaac actgaccaca tagagagagc 265740 tgcccatctg ccctcagtac caaggcacat cccatccatg ccctaaaact cttgtaaatt 265800 tctccattca aaaa tgagtatttc caat atgaccgtgg aatttgatta 265860 caaaaacact cctgctatcc ccaacctgtg ctcccagggc taaagacata tttgcaactc 265920 ttct tcac ttgtttgtac tattgagggc aacagttgtt ctcaaacaag 265980 gatgcagttc tctt accctgctta tttttctttt tattattatt attattatac 266040 tttaagttct ggggtacatg tgcagaacgt gcaggtttgt tacataggta tacatgtgcc 266100 atggtggttt gctgcaccca ccaacccgtc atctatatta ggtatttctc ctaatgttat 266160 ccctccccca gccccacagc cctcaacagg ccccagtgtg taaagttccc ctccctgtgt 266220 atgtgtgttc tcattgttca actcccactt ataagtgaga acatgtggtg tttggttttc 266280 tgttcttgtg ttagtttgct gaggatgatg gtttgcagct atgt ccctgcaaag 266340 aacatgaact catccttttt tatggctgag tagtattcca tggtgcatat atgcaacatt 266400 ttctttaacc agtctatcac tgatgggcat ttgggttggt tccaagtcct tgctattgtg 266460 Page 177 715825 ‐ Sequence g.txt aacagtgctg caataaacat acatgtgcaa ttat agtagaatga tttataatcc 266520 tttgggtata tacccagtga tgggattgct gggtcaaatg ctag ttctagatcc 266580 ttgaggaatt gccacactgt caat ggttgaacta actc ccaccaacag 266640 tgtaaaagcg ttcctatttc tccacatcct ctccagcatc tgttttttcc tgacttttta 266700 atgatcgcca ctgg tgtgaaatgg tatctcattg tggttttgat ttgcatttct 266760 ctgatgaccg gtgatgacga gcattttttc atgtgtctgt tggctgcata aatgtcttct 266820 tttgagaagt gtctgtttat atcctttgcc cactttttga tggggttgtt ttttttcttg 266880 taaatttatt gaagttcttt gtagattctg gatattagcc ctttgtcaga tgggcagatt 266940 atat tcccccattc tgtaggttgc actc tgctggtagt ttcttttgct 267000 gtgcagaagc tctttagttt aattagatcc catttgtcaa cttt tgttgctatt 267060 gcttttggtg tcttagtcat gaagtctttg ctcatgccta tttcctgaat gcct 267120 aggttttctt ctagggtttt tatggttttg acgt ttaagtcttt aatccatctt 267180 gagttaattt ttgtataaga tgaaaggaag ggatccagct tcagctttct gcgtatggct 267240 agccagtttt cccaacacca tttattaaac agggaatcct ttccccattg tttg 267300 tcaggtttgt caaagatcaa atggttgtgg atgtgtggtg ttatttctga ggcctctgtt 267360 ctgttccatt ggtctatata tcttatttgg taccagtacc atgctgtctt tgttactgta 267420 gccttgtagt atgaagtcag agacacaata aaaaaagaaa attttagacc aatatccctg 267480 atgaacactg atgcaaaaat cctcaataaa atactggcaa acctaatcca gcagcacatc 267540 aaaaagctta tccaccccga tcaagtcggc ttcatccctg gaatgcaagg ctggttcaac 267600 aaat caataaacgt aatccatcac agaaacagaa ccagtgacaa atga 267660 ttatctcaat agatgcagaa ttcg acaaaattca acagcctttc atgctaaaaa 267720 ctctcaatta actaggtatt catggaatgt atctcaaaat aataagagct atttttgaca 267780 aacccacagc caatatcata ctgaatgggc aaaagctaga agcattccct ttgaaaaccg 267840 gcataagaaa agaatgccct ctctcaccat tccttttcaa catattattc aaaactctgg 267900 cgagggcagt caggcaagag aaagaaataa agggtattca attaggaaaa gaggaaattc 267960 aattgtctct gtttgcagat gacatgattg tatatttaga aaaccccatc gtctcagccc 268020 Page 178 715825 ‐ Sequence Listing.txt tcct taagctgata agcaacttca gcaaagtctc aggatacgaa atcaaagtgc 268080 aaaaatcaca agcattccta tacaccagta acagacagag agccaaatca cgagcaaact 268140 cccattcaca attgctacaa agagaataaa atacctagga atacaactta caaaggatgt 268200 gaaggacctc ttcaaggaga actacaaacc actgctcaag gaaataagag aggacacaaa 268260 caaatggaaa aacatcctca tggataggaa gaatcaatat aatg ttgc 268320 ccaaagtaat ttatagattc aatgctatcc ccatcaaact accattgact ttcttcacag 268380 aattggaaaa aaactacttt agatttcata tggaaccaaa aatgagcctg catagccaag 268440 ataatcgtaa gcaaaaagaa caaagctgaa acgc tacctgaccc agcttatttt 268500 tctacatagg atccccacat ccctgctttt gctagaatgg aaactagaca aggaccaact 268560 tttatcaact tgttcatttc tctattccta gaacacagcc tggtacaaaa tttgcgttta 268620 ataatgtttg ttgaatgaat ttgaatgatg gatttgttta ttat aacatcccat 268680 gccttatgag tttgttgcca gaggaaaaaa gaagcctgtt tttggttcat aacatcaggt 268740 atgtaacctg gaatttggaa tcatgagttt ttatgcattt tatt tttt 268800 aagagatctt tcaaagtatt gata ctttaagatt gagagcctcc ctgataaccc 268860 aggaatgaga gttttagatt aagtttacaa tatgattgaa ggctaatcat ataaggagaa 268920 aaaaataaga aaaagaagag gaaa agaaatctcc aaaatggcca tggacatcag 268980 aacactgaga attcatacac aaaaatgtgt tttgcttcat acctgtctgt tgcacatcta 269040 tcat agatgcagag gaattttggc taaattccta acacatgaga ggcattctgc 269100 acttacttct caaattagaa ttaacacatg agtatgtata ttag agtgggcatc 269160 tatttaatga gtttactggc tgaatctttt aaaagaatgc aagt gccttttatc 269220 aaaaatcaat gaaaagataa aaggccctgt tgct gtggttccca cactacatcc 269280 cccacatcca cctgatgtca tcacaactgt ctatggtgtc catttgccac tatgcaccct 269340 gccgggcaga ctcaggtgcc ggca aagaccctca gctcatgtgc aggtacagcc 269400 tagaagtgca tgggggtgaa tgag gcacccttca accagtgagt actgggagcg 269460 gtagataaat atcctagcct ctcatctttc tacacaacag tggtggtgca tattctacac 269520 agcttctcaa aggagcctca gagggattgg gccccattag ccactgtgat aaccagctca 269580 Page 179 715825 ‐ Sequence g.txt gaacacacac atattagttg ttctcccttt ccttcccacc ctccccattc cctgactgct 269640 agatccagaa gtcatcttcc agatgaacta cctatatcca aatcctaatc tctagctctg 269700 gtttcttaaa caggtcctat gaaatgcttg aaataaaagg caaaatggtt tgtgtctaga 269760 atcaaaggct gacaatggca agcaacaggc actaaaacta tgacccagga aaaatgcttt 269820 tctggaagac atcggcatta cctcctagac acggaataca ctggcttcat cccagtagtt 269880 tcttcacaca atac gtgtctcatt aggatcacat atgactcacc tgatttcatg 269940 ccttgccttt tctttttatt ctgcagattc ttctaaggag cctaaattca gccg 270000 tgag actt gcca ctggacagat gaggttcatc atggtacaaa 270060 gaacctagga cccatacagc tgttctatac cagaaggtgc caccatcatg cctttctgat 270120 tttcctctcc atggatgtac ctactaaagt acactgagtc agatgtactg tgggaatgga 270180 agtgatttgt tgtgatttat gcaatcaatg aatattcatt cactcattta ttgaaaaaaa 270240 tattaatcaa gcccatccta tgtgctgagt actattttag gccctggaga tatagcagtg 270300 attacaaaag acaaaatccc tggtctcatg gagatttcct tccaatgcag ggagacaggc 270360 aataaaaatt gaattaaatg tcagctagta atataggtta ttaagaaaaa taaagccaga 270420 aagcagcata tcagcagtgt gtgggagttt gtgtatgtgc atgagaatgt gtgagagtgt 270480 gtgt gagc atgtatggat acacgtgggc atgtgcatgt ggatgagagt 270540 gtgtgtaaaa ggcttgaatg atgctgaaat gcgtggtcct aggaggcctc tctattgtgg 270600 tgtcctagac cagagacata agtgaaacgg gacaggccac gtgagtatct gggggaaagg 270660 ctatgcaggc agaggaaatt gcaagtacaa agtccctgag gcagtcttgg catatttgag 270720 aaaa ggccagcact gaaggcacaa gattgaaagt gaggagagtg gaag 270780 ggatcagaga gttacttagg gactgaccat gccaaacctc ataggcaagg gcaaggcttt 270840 gaattttact ttatttgtgg tggaaagctg taggtgtttt tgaaaagata tatgctttaa 270900 tagc tttgtttcta accagataat acactccttc atat attcagtaaa 270960 agactgtagt actttttcat ttttaccagt gaccctctaa aataacagag gaagggtgaa 271020 acaaagacct atag gtaccatcca ttat ttcttcccct tcacctggca 271080 ttattttcat ttttgtttac tctcactgtg tttc ccttttttac attttaggct 271140 Page 180 715825 ‐ Sequence Listing.txt taaacacttc attatctcct gttttccacc caacccccag ccta agccaagatg 271200 cagggttagt gaggaccctt tatccttggc tcaaggtgtt cgttagtcag aggatgacat 271260 tgtctatcca accgaagagc tggaataggg aaggaagatg gcag ttaagggtat 271320 gagctcaggg ctaacaaacc tgcacttcag tgtagttctg cactttctca ccaaggaata 271380 ctagggaaat gttt gtgtacaact cagcctcctc atttgcagaa aggagataat 271440 ggacttgcct catgacttct tgtgaggatc atatgagata acccatgaaa aatacttggc 271500 agagtacttg acacataata agtactcact tagc tggtattctt cttatcggta 271560 gtatagtgat aattttaaaa taattatgat atagaaatcc agttcctgga ctataaaatg 271620 actataaatt gtataagacc atttatacca gtaaattgtt ataattattt ttgg 271680 tataagagca ttttaatgca gagctgctgc ttaatttgca aaaa tacttggagt 271740 tagcaaccaa gcagaccttc cccacctttc agtataagag aggtctcttg gatgaagtga 271800 agtgaagatg aaatgtttgg gcaccaagta tactatattt ttccttaagg ctgacaccac 271860 agagaggttg gggccagtaa acagagttga tttctataaa tacattcaga catgaagtta 271920 gtatgtttga tgacactttt gaaatgtgtg gaatcattaa gttatttgta caggcacaat 271980 tagccaaact gtaaagaaaa gtagcagaat aacctcttaa gctgggccca ctttatgaaa 272040 ataatttttt gctacctcaa tatttaccaa atttgatgag caaaaagaga aagg 272100 aatgaagcct tgataaatat atatcccttg tcaa tcagggtcac ataactctgt 272160 gcat cttatgcaca ctccagtcat atct ctggttcaaa tccaggatct 272220 acactaccaa ggatgctgct gaaagtgtga aaag ggaaacgttc agacatattc 272280 agaaagatgt cttagatttt gccctggtag tgtttggaat cccaggaggg taagtacagc 272340 ttcatgatta agtgccaacc caaacttaca aaattagata tttgtgtttt ttctataaaa 272400 tataactatt ttgaatatct aact actatgagcc cacagcccag tttatccaag 272460 aaggataaaa ctgagggatt aggagtatca ggactggact ggactgatta agtt 272520 atatttgatt tctcattgcc cacttcacag agaagacaat acaaatgcac tttctgactc 272580 ttatcactgt ttcttagaac tcagttgcca ggcaactcct gaaactatag aaacatgctt 272640 ctcatccctg acacataaat aaaactctga gatgatttta tccaaagtca gagtcagtgg 272700 Page 181 715825 ‐ Sequence g.txt gcagtgcagt tgtttcagtt tgctggcctg gcctcagtat ctaaagcaca cgtg 272760 aacatgtcag gctgtcaaca ggacagttca ggcacagccc cagt tgtgtgtttt 272820 gcctggctct gctccttgcc aggtggctgg cagaaaaggc agcctccaca tgttagagca 272880 gcagattcaa aacagtgtct gccatcctgt gatgacgata gtgccaaatt cagcctctga 272940 gcttgcaggg gactcaggat gaatgcacat tacaggcatg gtaaaaagag gctctgggaa 273000 gcatgttcga ctgc tctcagctcc ttgcatgtaa atgctgtgtt tttaaaggaa 273060 gtgggcatgt gaacactcag tccttaaggc tgtatccccc acctcttcca tacccattca 273120 accccacttc aaaaattacc ctggtcttaa tttc attttctata caaggttgtg 273180 tggaaaatca gtagggagaa agggcattat tactttcatt tttctttaac atta 273240 aatttaaagc caaaaacgtg cgctttctgt catgaaaaca gctgccctta aaaacataaa 273300 tgatgtttta tttttattac ttttatctag ttggttgtct ttagatgaaa tctt 273360 ctgctcttta ttcttatttt taatgatagt ctctttctat ggttctcacc ccttccattt 273420 cacaagatag agca aacctaaagc acttaacttt tgggagtaag agcagagggg 273480 cata cattgatttt ggtcatctgt agagacattc aacccagaga aggcaagtga 273540 cacagtatct gttttatgag ctaatttggg ttcttgtcta catttaatag tttaaaatat 273600 aagttataaa ttta aaatgaaatt caacattggt tcatgaagaa agaggttgga 273660 agtagtgttt tgaactagct gtttctgatc catcatgctt aaaataaatg ctctgtttgt 273720 cctgtggagt tcatggattt gggataatct aaacagggtt ttttaaacag tggg 273780 gaacaaggta ctgacatgca ctgttgagaa attctgtgaa tcatgaaaga gctaatcttt 273840 tagaaatcca gacctgttaa gcactaatct acatctttgg aatatcttaa gagt 273900 tttctaactt ttatactatc gcta agtacatttg atatcccttc tattatgtga 273960 aagcctcatt ttctgggcaa ttttcttaca actactctct ttaatgcact cttacttaat 274020 ttgaaagtaa atatcaaatt aagcatacta tagttcaatg aaccacccac ctattcctaa 274080 tttttttaac atttctcttc tgactctaca cata cttacacaca cacacacaaa 274140 cacaccttat cttttcttct gccttttgcc catttacttt caga gatgaatctc 274200 tcattcaagc atatgcaact tttttttttt ttgagatgga gtcttgcttt ggcacccagg 274260 Page 182 715825 ‐ Sequence Listing.txt ctggagtgca gtggctcgat cttggcttac tgcaaacttt gcctcctgcg ttcaagcaat 274320 gcct cagcctacct accgaatagc tgggattaca gaagcatgcc ccca 274380 gctaattttt gtatttttag tacagatggg gttttaccat gttagccagg ctggtctcaa 274440 tctcctaacc catgatccgc ctgcctcagc ctccgaaagt gctgggatta caggcatgaa 274500 ccaccgtacc cagccagcat cttt taagagtctc agca gcaattcact 274560 gtctcagacc ctggagtctc tgccatttaa atcccaattt ccttccaaca gctgaggagc 274620 agctgtctca ctct gatactacac aagttttctc ctagtgccaa cagc 274680 ctgagaaaca gctataagaa ggaaataggc gtcttctccc agcttggcat cctttccttc 274740 caggccctgc cttccctaca acctgcattg tcttcattgt ccactgctgc ccca 274800 tcccacagag ggatggtccc aaacctccac agtctggcct gtgagccaca ggcgcctctg 274860 cctgcacagg gccattccta cctcatcttc cacaaccaca gattacatgg ttttatgtcc 274920 ctta tatattgtct tctcaattaa taggctagtg aataacatgg agatgatgaa 274980 ctacctcacc caagtagcaa ttctaattta agaaaatttt cctgtcattc cattgccttt 275040 tacttccatt accacactca tgcccatact tccttacctc aatccctttg acctctctgt 275100 ttattccctt ccttgccgta ttgccatcta ttaaactttt acccatcctt caagaatgct 275160 aaaaacatac cttg aagccttcca tgaagagcca gagcaatcat tccctcttct 275220 gaacttttaa ggaccctaga tact aatgagcact catt gctttgtaat 275280 atggtttttt actctttcct tctgaggcag gaggaattcc ttagacatct ccca 275340 tagtgtctgt cattatgttt tagacataac caattctcat taaatgtcaa tagaatgaat 275400 ataagaggcc caaaaaacta tggg aatttgagtc ttattttagc ctgaaattag 275460 gggaccacat cttacttatc tttatatctg cacagcgttg gtgctggata taatgcatca 275520 ctctgcctgg agcacacatc aacttgtctc ctcagtttct ttcaccatag gctggtgaaa 275580 cagccaggtc taaaccttca ctgttctctg ggaatctcta gtttgggggt gattctctgt 275640 actgttttaa tgaacatttt taaaatgtcc ctaagtctca gaaccttcat ctatacaact 275700 ataa tacc ataggaatcg atttatgagc aggcatagca tattcattca 275760 ataaacggaa gttttaccat aggcagaagt accaaacggc ctcgtagcag tcgtcagaca 275820 Page 183 715825 ‐ Sequence Listing.txt ctgatgatac tgtccactga tgtgatatgt ctcggaaatg ctaa aatacctctt 275880 cacaaaatat ttgtcttcca tgaa tcagactatc aagcacctta cttggactta 275940 agctacaaca tgatttttgg aacaattaat ctttttttaa cccttcattt taggaacact 276000 caagaatgga ctcaagaatg gaaagaatgc cctgattatg tttctgctgg ggaaaacagc 276060 tgttacttta cgtt tacctccatc tggatacctt attgtatcaa tagc 276120 aatggtggta cagtggatga aaagtgtttc tctgttgatg aaataggtaa atcacaggtt 276180 tttgtttcat ttgacatagt tttagactaa ataaatgggg aagcctgcaa ggtccaagta 276240 taatcaagta ggaagacttt gtaacagtgt tctatagata catggagatc tgttttacag 276300 gagatgggat cagctggtga ggaa aagggcaggg taag ttgactttaa 276360 cataaagtag cctggcagta aatgttgtga agaagagaat aggaaccttg tggagtcttt 276420 tcctttagga tatctttgaa gctgcgttgt gtttttatgt tccactgcaa agggtgaact 276480 taatatattc ttaggatttc ttacttccta attatttgat aggatcctta tattcaaatt 276540 cactgaaata cgttggcctt tgacctctac cattgctgta atcaaagcct agattttctt 276600 tatcacaaag cataatcatt ctggaatttt acatttacaa aacagccaca ttaa 276660 agacatgttt attagatctc agaacaaata ctggagacaa tcagctcagt gaactaagtg 276720 aaagatccaa acagaggatc ccat catatggaca caaggtggaa acaaaacaaa 276780 taaaacaaac aattgtaatt agaatagtca tacc ttaatagtat aaatagcaaa 276840 atagaaagaa tcaaagaagg actttgagta gctgaaatta gtgcctcaaa atctatccac 276900 tcat ttgttgctta taggaatttc tcgttgcttc tcccaaatgt attgttcttt 276960 ttatgtggtt gcat aagctgactg gaagacatag gagtatgtgg ctagaactta 277020 cagatagaaa caaataaaat ctaataggct aagg gagaagatta agagaactgt 277080 atcaagcagt aaagataacc caattgcttt gcaaagacaa tttagtatgt gtcctaacat 277140 cactgggtat agctgttgag ctaa atgggatagc agaatgggat agtagcaaga 277200 acactgggtt aaaacccatg ttctagccct gttctctgcc aatagccagt cctactcatt 277260 tacctggctg ctgt catgtgtcac gcactgttct ggtggtggtg gttatagaat 277320 aagtacaata cagtcaaaga gggaagtcag gcatgttcac aaataattgc agtgcagcgt 277380 Page 184 715825 ‐ Sequence Listing.txt gataggtgtt agcctggaaa tacgtggaat gcagagctgc aaaggtggtg gccaaaggcg 277440 tgaatgactg acaggcctga gggatgagga agggctgcac agagatggtg acagtttagt 277500 tacctctgaa ctggaattgg actctcccta aaaa agtgatgacc cacagtggtc 277560 aaaagcatga gtgagtattg tcaggtacca cagtggactt gcctttcagt aactactaag 277620 cagt aacttagtag ttacttagta attacaacag taacttagta gtcccaacat 277680 gttcagggac tcaggagcag agcc ctcctagtca gctggagaaa tcatcagtag 277740 ttgtttgtgc cccaaaaagg aatttggact ttaactgtca cgaggtacct ttgaggatgt 277800 aggg aaattacttg aggatactaa tagttaacag tcacaaaagt cttaccatgt 277860 gtcaggtata aaaaccatct tttgcaatca cactttacag aaac cgaggcacag 277920 agcagttaaa gttc aagtcaaaca gctagtagat agagctggga tttgaacctc 277980 cagcctccat gctcttactc ttgaggcttt gcagtaccac ttgtctcttt attaatgctc 278040 agagaaatta atcttgttgc aaac gtagattgga gtgggacgga ctagaggtag 278100 aagaggttaa aagactgaga tgatcaaggt aaaagattat gacaggtagc tacaactagc 278160 acaatagttg tggggcaagg tgctgagagt gaaagagaac aaagaactaa tgtaaccctg 278220 gtagatcttg agaaagttgt caatcattat aagcctcagc ttcctcataa aatatgtatg 278280 tatggtacta cctcacaggg ctattctttg gatttgaagt actatattag attt 278340 gtcattcatt caattcattc tatt tattatgctc ttctctcagg ccagtcaatg 278400 ttctccatgc tggggataga aactgtcttc cctggtggga tttaatccca atgg 278460 aaagcgacaa tgctatggag aaatatagga aaggagaata ggagtgttgg agaggttgca 278520 agtt ttcaggattg gcatccctga ggcagtggca tttgaataaa gaaggattgg 278580 agaggataat tatgtgtgtg tctcagggaa gggcatttca gcaagggggc acgccagaag 278640 aaagatctca aagtaggagc atgcttttcc tcactcaatg aggc cggcggtgga 278700 acag agtgagcgag gagactggta tgagaccaaa tcgcacagac aagacagtca 278760 aatctaccca accattgcca aagactttgg ctttcacttg gagtgaggta cttt 278820 ggagggtttt agatgatgag cgatgtgatc taacgtaagt gttaggataa tcactgtgtc 278880 agttcgcttg aggattgcat ggagaataga gggg acaaagacca aaggggtaca 278940 Page 185 715825 ‐ Sequence Listing.txt gtggggagac aaatgaagca agaagaatga aaaaggataa ggac caggttatta 279000 gtggtgcagg cggtgggaca tggttggatt ctgttatatc ttgaaagtac cgga 279060 atgtggatta gtgaggaaaa gatgagccaa ggacaagttc attgttttta tcctgagcaa 279120 ctagaggaat tgagtcctcg ttaacagaga tggaaaagag gaaaggagag caggttttgg 279180 agaggaagag caagggtttg tttggggata tattaagttt cagatatttt ttaaatatct 279240 cacaggagtt atag catgtagatt tatgtataga gataaaggag aggtcattat 279300 tatgcctgta atggtatctc acaggaggtc attgttatgc ctgtaatggt ggtaccaaat 279360 cttttccaaa aggaccttgt ctcatatcct ctatttttca aatgcagcat aagtaatgag 279420 ttatagaaaa tcttccatta aaaacaattt tatagtttgg tcactttaaa cggttaagct 279480 ttgattatca ggattcctga atctccaaca aatccagaag ggtgaggaat tattgccatt 279540 atatcggcat atgtagtttg gccattttgc atatccttcc aatttaattt tcaaaatgta 279600 attc atcaaatttt gactctccct gtttttaaaa aggtggtgtc gaccccacag 279660 agggcaacag catgctcctc caccataagg cctgttttca ctgtgggtgc acacaagagc 279720 ttccctcttt ggccaacaga agcc agtaagagct cctcactgtg tatatctgta 279780 aagttatctc cagtcaacgc tagggatgca cactctgcaa cactctaggt ggccttctgt 279840 atatatggca gaaa gtaaatttta atct gcaagtgatt ttcaaaaccc 279900 tcagtaatga acta gcaaaaattt aact ctctagaata taga 279960 catagttcct agctttggaa tccatatttt tcttcatcag cctctgagaa attgtggtct 280020 ttgaggtcct actaagcaga atgcaacaaa ttttcgtgga actgtagagt atatcaatag 280080 aacctgagga aaacaatgtt tcaagttgtt catgtgacag tcaaaaagac agaaaacact 280140 gaattgtcac catttgtgag actagcataa tgctttcttc cttcttatgt cagaagaaaa 280200 tatcacatgt gaag atcacaaagc tagggagcat agtg tgcaggaaga 280260 ttgtatgaga agattgaaga agagtaaaaa aggataatgg ctaggaccag gttatagtgg 280320 tgcaggcggt gagatatggt tggattctgt tatatcttga aagtacagct gacggaatct 280380 gacggaatat ggattagtga ggcaaagatg agtcagggaa agaa atgaggtaaa 280440 cagggtctct aggc tagt tgcaagaaaa aaggtttctc tacccctagt 280500 Page 186 715825 ‐ Sequence Listing.txt gcag ccccatgtct aaattctgta agtctttctg tgtt ttttcagttt 280560 caagtgaaaa taaattcctt tgccaaaatc ctgatgcatt atca gagcaaaaag 280620 aaatatacaa catggcagat cttgtaaata gtgatcagat gttttactcc aaaaggaatt 280680 tttgtaaggg cttatttaga agttaaaaac aagtcatcct tgagttaaaa aaaaaagtta 280740 ctctcttata aagtgaaagt tataataaga aaaatattgg aagaaataag agcatgaatg 280800 atcaaaaatg tagaaagtaa tttggtcttc tgagaagaat gccttccatt aatattaaat 280860 tgtgtctgtc ctaa tgctctgttg aattgcacag tgcaaccaga tccacccatt 280920 gccctcaact ggactttact gaacgtcagt ttaactggga ttcatgcaga tatccaagtg 280980 agatgggaag caccacgcaa tgcagatatt cagaaaggat ggatggttct ggagtatgaa 281040 cttcaataca aagaagtaaa tgaaactaaa tggaaaatgg taagatgttg ctacacctta 281100 cactttgact tttctttcta tttcaacaaa ctctctctca tttatcatta gactttcctt 281160 tgacctaata ccacatgttc atgctgtatg ctccataatt ttga gaaaacatta 281220 tttaaccggt aaaatattgt cttgaaattc tgtaagacag gagatgctta tgtatatatg 281280 gaggcctgtg aagg aaaactattt ctccattcat tcttgctgtc cagtttaact 281340 ttagagcaaa attatagact ggccacttag ctgtctttgg ggatgtggat aaaaatggga 281400 aagtttgtga tccagtcaac agtgactatg gccaaatatt ttcccatgat ttcagttgct 281460 gctactcaaa ggactcccac taaaacaaat tcatacgtgt ctataggaaa acagagggag 281520 ggaatttgtc tcttagaggt ttcagaagga tgttttgtta catacctcag agaagaatca 281580 gatt cttatgtagg caattagaga tacc agttgacctc cctc 281640 tcttccttac caagcatatg gaactcagca ttttgataaa atgg cacataacaa 281700 gaggaaaaac aggagtatca tgctgctccc aatataacta attctaaatc tgtctaacca 281760 cagc cacagccaca gccaagccaa gcagtttctg catc aggtgatgcc 281820 cctg gcacagatca ctcccagaat tttgagacac caggacattc agtgagccac 281880 tgaaaaagat gccaattttg tcattagagg aaagttaagt ttggaggaaa tttgagtagt 281940 tacaatactg gagg ctctattttc tgaatcattt taatttagat tctg 282000 taacttggta caaataaaat gcctgattgg atgctaagtc aaacaagact gtctaaatcc 282060 Page 187 715825 ‐ Sequence Listing.txt aagctacaat caaacattat ttaacaacag gtactgaaat aactactatg cagaaggcac 282120 tgtgctaaat gcctgaggtg gcggttctca aagtgggagc cacagaccct tgagggtccc 282180 cctt tcagggagtt cagtactatt ttcacaatac actaaaatat tattttatta 282240 actatgttga aatttaactt aatggcacaa aagcaatgct ggaaacactg ctggcacctt 282300 agcatgaagc aaggcagtag gatcaaattt tactaatagt catgcactcc caatgaagaa 282360 aaaa gccagtttca cgtttgaagt tcttgatgaa gctgtaaaaa ttgttaattt 282420 tactaaacct cgacctttga gtacatagct tattaatatt ctgtgtgaca tatgggaatt 282480 taag catgtctgct gcgtactgag gtattgtatt tgtcttgaag gctt 282540 aaatgactga gttgccagct gaactagttg ttgc ttggagcacc atttttactt 282600 ggaagagcca ttgataaact ggcagatggt tattcatatt tgaattggca aacatttgtc 282660 gaat gaggcaagct tgtcgcttca agaaaaacaa ctgacagtat tttttgcaat 282720 ggaaaaaatt tgacttttca aagcaattca cttt ttcgaaaatt tcca 282780 accgtgagct tgatagtgtt ttaatatttg aagacttttc ttgaagagat tgatggtgat 282840 attaatgaaa gtgacttttt aattatattg tgtaataaaa tgtatgaaca aaaa 282900 tctacaactc agttaaccaa tattttccaa attactaata catgatgtaa tcaaatcatg 282960 catggggaaa tgatccattc ctag atagaatcgt gaattttttt aatgatcaaa 283020 aatttttttg tatatttatt gtgtacaaca tatttttttg aaatatggat acattgtaga 283080 atggttctat cacactaagt aacatatgca ttaccacaca tacctttttt tgtgtgttga 283140 gaacacttaa aatctactca gagattttca aata cataagcatt aactatagtc 283200 accattttgc acaatagatt tcttaaactc attcctacta actgaaaatt ttaattcttt 283260 catcaatatc tccttaactc ctgc ccacaacccc tgataaccac cattcaactc 283320 tctg agttcaactt ttttagattc tgcatataag tgagattatg tggtatttgt 283380 ttttctgtct ctggatcatt tttcttaata taatatcctc caggttcatc cacattgtca 283440 caagtgacag gatatccttc tttttttaag gctgatagca ttccattgta tatacctacc 283500 acattttctt tatccactta tccattaatg gaacataggt cgattctatt tcttggctgt 283560 tataagtaat gaacatggga gcccagatat tctggctcaa gatt tcattttcct 283620 Page 188 715825 ‐ Sequence Listing.txt tggatatata cttagtagtg gaataatata atggatcaca tggtagttct atttttaatc 283680 ttttgaggaa gcttcatatt attttccata gagggtatac taatttacac tcccaccaat 283740 agtgtgcaag ggttcccttt tgtccacatt ctcaccaaca cttgttatct cttctttttt 283800 tgaaaatagc catcctaaca tctttgtgca ctctatgcct tctgtgagct gatagctcat 283860 tgtggtttaa atttacattt ccctgatgat taaagatgtc aagcattttt catatacctg 283920 attt cttc tttttaaaaa tttatattca ggtcctttgc ccatttttta 283980 attgggttat tttcttgtta ttgaattgtt ttagttcctt ttca gatagtaact 284040 tcttatcaga tgtatgcaaa tattgtctcc cattccatag agtgtctttt tactctgttg 284100 attgtttcct tggcagtgca tttt agtttcatgt aatcccgttt ttcc 284160 acttttgttg cctgttccca atggagtcat atccaaaaaa tcattgccca aaccaatgtc 284220 atggagcttt ttcctatatt ttcttccagt agttgtacag tttcaggttt tacatttaag 284280 tctttaatcg attttgagtt tatttttgta tatgaggtaa aataagggta taatttcatt 284340 cttctgcata tggatgtcca attttcccaa caacatttaa agacagagtc ctttccttac 284400 tgtgtattct tagcaccttt gtgataaatc aatttactgt aaatgtgtgg atttatttcc 284460 gaacacttta ttcttttaca ttggtttatg tcatttttat gccagtacca tgctgttttg 284520 atag ctttgtatta gagg ttggtagagt gatgatttca tccttgttct 284580 tcaa gattgctttg gctattcata gtctattgca gttgcataca aattttagaa 284640 ttgctttttc tatttctgtg aaaaatgaca ttggaatttt gataaggatt gcattgaatc 284700 tgtagattgc tttaggtagc agggacattc gaacaatatt aattcttcta atccatgaac 284760 atgggctatc tgttcattta tttgtgttgt cttcatgttt tacagttttc agtgttcaga 284820 tctttcacct ttttgtttaa atttatttct aggtctttta ttttattttt atttttatag 284880 atattgtgaa agggatttct ttatttcttt ttgt tccttattag tgtatagaaa 284940 tgttactgat atgt tgta tcctgcagct ttactgaatt tctg 285000 caat tttttgttga agtctttagg gttttctata tataaaatca tgtcatctgt 285060 aagcaaggac aatttaactt tttccttctc aattttggat gccttttatt tctctctttt 285120 ttgc tctgactagg attttgaatc gagtagaata gagtagagga gttacattga 285180 Page 189 715825 ‐ Sequence Listing.txt ataaaaatgg caagagtagg catctttgtc ttgttcctca tcttagaaga aaagctttcc 285240 acatttcact gtttattatg atgtgagttt gttatatatg gcctttattg tgttgaaata 285300 cattccttct aatt gttaagggtt tttatcatga aaggatattg aattttgaca 285360 agtgcttctt ctgtatctgt tgagatggtt ccatggtttt cgtctcggtt ctgttaaagt 285420 ttat gtttatgtat ttgtgtgtga tgaaccatcc ttgcatccct ggaataaatc 285480 ctacttgatc atggagaatg ttccttttag tgtgcttttg agttagtttc tttt 285540 gtttaagatt tttacatctg tatttatcag agatattagc ccataatttt ttgt 285600 agtgtccttt catggtttgg gtataagggt aatgctagca tcaagaaata gtttggtagt 285660 atcccctttt cttccacttt ttggaaaagt ttgagaagga ttggtgttcc ggtgaagctt 285720 ccagtgaaac tgtcaggtcc tggacttctc tttgatgaca gactttttat tactgattca 285780 atctccttac ttattattgg tttattagat tttctatttc ttcaagaaag tagg 285840 ttgttgtgtg taggaattta ttcatttctc atgcatataa tttttcagaa tggtctctta 285900 tgaacatttg tatttctatg gtattggttg taatgtctcc tccttcattt ctgattttgt 285960 ttttaatttg ggctttctct ttttttatta tttagtctag ctaaagattg gttgattttg 286020 tttatctttt caaaaaaact atta atcttttcta ctgttttaat gtgctaactg 286080 aaaagcacat taaaaggatc attctccatg atcaagtagg atttatccca gggatgcaag 286140 gatggttcat cacacgcaaa tacataaaca taatacatca cattactaga accaaaaaca 286200 aaattatgga accatctcaa tattttctat tctctatttc atttatttct atct 286260 ttattatttc cttccttcta tgaactttat gcttagttta ttctttttct ttca 286320 atgt attc gatc tttgttttct gatggaggca tttattgcca 286380 tgaacttcca ttgctcttag aacgactttt actgcattcc ttaaggtttg ctatgttgtt 286440 tccatttttg tctcaagata tttttgattt tattttttac tttttaacta tttttttagg 286500 ttcagagata cacg tttgttatat aggtaaattg catgtcacag gggtttacca 286560 ttat ttcatcacca ggtaataagc atagtaccca gaaggtagtt ttttgatctt 286620 caccttcctt ccacccacta ccctccagta ggccccaata gttt cagtcttcgt 286680 gtccatgtgt tctcaatgtt tagctcctac taataagtga gaatatgtgg tatttgtttt 286740 Page 190 715825 ‐ Sequence Listing.txt catg cattagtgtg cttagcataa tggcctccag ctccatccat gtgactgcag 286800 aggacatgat cttgttcctt tttacgcctg agcagtattc catggtgtac atataccaca 286860 tttcctttat ccagtgtacc attttcttta ttccatgtct ttgctattgt gaatagtgct 286920 atgatgaaca cacgcatgca ttta tggtaaaatg gtttatattc cttcaggtat 286980 aata acgggactgc tgggtcaaat gacaattctc ttttaagttc tttgagaagt 287040 tgctaaactg cttgccacaa tggctgaact aatttgaatt attaccagca ggatataagt 287100 gttccctttt ctttgcaacc tcaccagcat ctgttatttt ttgacttttt gataatagcc 287160 actg ctgtgatgta gtatctcatt atggttttga tatgcctttc tctctaatta 287220 ttagtaatgt tgagcatttt ttcttacact tgttggctca tgtttgtgtt aaaa 287280 gtgtctgttt atgccttttg tccatttttt aatgggactg tttgtttttg gcttgttgat 287340 ttaaagttcc ttatagattc tggatattag acatttgtca gatgtatagt ttgcaaatat 287400 tttcagccat tctgtagatt atctgttttt tcagttgttt cttttgctgt gcagaagctc 287460 tttggtttaa ccca aatt tttgtttttg ttgt ttttggcatc 287520 tttgtcatga aacctttgct aaggcctatg tccagaatgg tatttcctag gttttcttct 287580 agggttttta tagtttgggg ttttgcattt ttaa tccatcttga agtc 287640 gtacatgttg aaaggaaggg gtccagtttc aatcttctgc atataactag ccagttaccc 287700 agcaccattt attaaacagt gttttcctca tttcctgttt ttgtcaactt tgtcaaatat 287760 tagttggttg caggtatgag gctttatttt ctct gttctgttcc attgatctat 287820 gtgtcttctt ttttaaccag taccatactg ttttgattcc cttg tagtataatt 287880 tgaagtcagg taatgtgatg cccctgggtt tattcttttt agttaggatt gctttgacta 287940 tttgggctgt tttttgcttc catatgaatt ttacaattgt tttttctaaa tctgtgaaaa 288000 attacattga gata gcat tgaatgtgta gattggcttg ggcagtatgg 288060 tcatcttaac gatattgatt cttctaatcc ataagcatgg aatgtttttc catttgcgtt 288120 atctgtcatt ttctttcatc agtgttttat agttctactt ataaagatat ttcacctcct 288180 ttgttaaatg tattcctagg tttctgtgtg tggc tataataggc tatgttaacc 288240 tgataacaat ttaactttct tgcataaaaa actctacact tttactccac ataccgcccc 288300 Page 191 715825 ‐ Sequence Listing.txt cccaaacaca attt ttgatgtcac acttacatct ttttatattg tctt 288360 aacaaattat tgtacctagt attattttta ataattttat acct tcattctaaa 288420 ataaaagtga tttgcatatt accatgaaaa tattagacag tgat gcccctgggt 288480 ttattcattt tagttaggat gcca attgggctgt tttttgcttc catatgaatt 288540 ttacaattgt tttttctaat tctctgaaaa attacattga taatttgata ggtattgcac 288600 tgaatgtgta gattggcttg ggcagtatgg taac aatattgatt cttctaatcc 288660 ataagcatgg aatgtttttc cgtt atctgtcatt ttctttcatc agtgttttat 288720 agttctactt ataaagatat ttcacctcct ttgttaaatg tattcctagg tttctgtgtg 288780 tgtgtgtggc tataataggc tattttaacc tgataacaat ttaagtttct tgcataaaaa 288840 actctacact tttactccac atactccaca cacacacacg ttttaaattt tcgatgtcac 288900 acttacatct ttttatattg catatttctt aacaaattat tgtacctagt ttta 288960 ataattttgt cttttaacct taaa aagtgatttg catattacca tgaaaatatt 289020 agactacttt aaattggact gtgtacttac ttttactagt gagttttata ctttcatatg 289080 tttttatgtt actcattagc ctccttttct ttcagctaaa gacctccctt tagcagttct 289140 tgtaagatag gtctgttggt gaggaatggt taatttaaat aagt acaaaaagtt 289200 catcagtaga gtttcaggtt tcatttttcc actaacctgt aagaatttat agtt 289260 ttagtctatt gttaaacaga aatgttcaca attatgtgaa aagtttatta aaatattcct 289320 cattttcctc attatttatc tgtgtgaggc caggttttat tcatttacga caca 289380 ttctaataga tttaattcag aagcagttat aaaaatacag tcatcttcct ttaagtctga 289440 cattaaataa atttgcaaaa atgtaaaaca gtatcactct tctcactctc ttttttgttg 289500 tttgggaaag tacaataatt tttatgaaaa tatattattt aacaaaatca atttattatt 289560 ttcagtttaa aaataaggat tttaaaattt ttca atttctaata ctgtaaatag 289620 tgataggtat acta aaccaaactc tttaagattc tcaaattttt aagagtgtaa 289680 aggagtcctg aaataaaaaa gttaaacaac ctagaaaaaa acaaagatat gcat 289740 gttagcattc atcaattcag ttaccatcat ttcatcccta aaagccatgg catatagtta 289800 cgtctcactg agccaccact ttgaaactcc caccctgtgc caggtacttg tgagcatgta 289860 Page 192 715825 ‐ Sequence Listing.txt ttaa tcaactgttc agggctatat cccaacatgg ctttgttgca cttttcgtgg 289920 cacctctgct aaatctcgtt aggtagacca aaggggtcag ttaacttttt ctttatacct 289980 tttattcatg ataa gtttggtaat ttacaaaggt cttggacaaa gaccaggggc 290040 ttatatataa taatttattt tgaa gaaacaaaca atataattgg ttatgaagca 290100 caggcgtcat aagcagaaaa caggtttata ggtaaagggg gaagacctag tgtgtgtcgc 290160 ttgcatcagg aattcatgtt accatttggc aatatgaatt tgcttagcag tgtgcttttt 290220 tttctccccc gatc ttgctctgtc ctag gtgg cccaatctcg 290280 gctcactgca acctccacct ccagagttca agtgattctc gtgcctcaga agta 290340 atta caggcgcaag ccaccacacc atac agctaatttt tgtattttta 290400 gtagagacag ggtttcatca tgttggccag actggtctcg aactcctgac tcat 290460 ctgccaacct cggcctccca aagtgctggg attataggca tgagccactg tgcctggctg 290520 ccctttttag taaatacatt ttgcatgacc atgtggttgt ttacagctat ttatctagta 290580 aaccaataac ttacagcttt ttaaaggctt aatgaatagc atggaattat tcatgatatc 290640 atat cttgaggacc cactgtatac ctgatattgc actggacttt ggaaatgaaa 290700 aataatgagt gggg caat gtaacataga aaggtgtgta tcactaaatt 290760 tgcacaatga aacataatta ataatagaag aagtatatta tctggcagaa tagagtgggg 290820 aaaagtacca gcaaagactt agaataccag ctctcctcaa tacttgcact tagacttgga 290880 tgagaaacag ttccccgcac aggcagatga cagggttagg tatgatagga gccacgtaag 290940 taggagccac tcgaaatctg agtttggtgt ggctggtgtg gagggttgag ggaatatgaa 291000 gagaggacca caacttgaat cactgagggc ccttttttga tcctattagt gaaatcttta 291060 aagaaattgt attggtgaca ataacagaga aataagggct ttgaggatga aaacataggc 291120 tttaaaaaaa aaacttaaga aaaaaataat aaagtaagtt cagtattcag tgtcctgcct 291180 taaagaaagc attttaggca tgcaaatatc ccatatattc agaggcttct ataaaaaata 291240 caaacaaacc ctgtcatata cacatgaggc aaaaaaagat actttgtgag tagaaactat 291300 tgaggtaaaa gaaaaacttg ttttagaagc tgaaggccca gctgctgact taataaaaca 291360 gaga attttgttta tgcgaaaatc gttg aaaacgcgag tgtttaaagt 291420 Page 193 715825 ‐ Sequence Listing.txt tttctataaa caggaacaag gtgttctacc aaaaaaaagt ataaaagcac attgaataac 291480 tgctttgagt atttgacttg gaggaaacta ccatcactag ttgagtatac ctctttgata 291540 gcaatatgtg ttaaaagtct aacagtctca ccct ccccgagaag gtaaaggaat 291600 atcctgacct taagggttgt gagacctaga tgtttcttac caaagaactc cggtgacttt 291660 tctttgcaga ttttaaatag caaactattt tatggtggct ttaagccttc cagagcaagc 291720 agattaggta tgtagttcct tttaataaaa gtatttggaa gttcaataaa ggcaattatg 291780 atttttctag ttcc aattctgtga ttatgtgaat gactacccgg aatttccatc 291840 aaacactgat cttg ctatggctac aatttatttt aaaa catgtttgct 291900 tttctgttct tatgtctccc ttcatacaaa agtataatat cccagatatg taggcatata 291960 gttctgccat tcagagtaat tctaatatac tttaatctta ttaactatct ggaagactaa 292020 gtta tagctgcatt tctttaagca agtctatcat atctttgggt ttatgccaaa 292080 ctaaatttgt gaactattat ccatttacaa aatgattatt tacatcaatc ttcctttaaa 292140 taacaaatgc tcacaatgca ttttaaaata ttacctactt aatc cattctgaat 292200 aaaaatggga gaatacctgt agtgttcatt gcattgagtt gttgactctt tggccaatat 292260 gcgtttatat tttgtcttga aagatggacc ctatattgac aacatcagtt ccagtgtact 292320 cattgaaagt ggataaggaa tatgaagtgc gtgtgagatc caaacaacga aactctggaa 292380 attatggcga gttcagtgag gtgctctatg taacacttcc tcagatgagc caatttacat 292440 gtgaagaagg taaaagaaat aaaagattaa aatagtagct aacctggctt ttgtcaatat 292500 aacagttgat tcacccctgc actggtagtg tgttgtccaa atcaaaatat attaacatca 292560 gatatcagga acct tgagctcact aaca gatattgttc attgcaaaag 292620 cagaaggaag atttagtttc caaatttttc attcaggaga agtccggggg gcaggtggaa 292680 gtttagagac aggaatttgg tggcaatctc cggatggtag aattcagatg attcttttct 292740 ttatatattt ttatatttct gaaattttct agtt tgttttgaat tcag 292800 gaaaaaaagc tgtactgatg gaag aaagtatgta tctatatgga tggatagata 292860 atct aaac ccaatattga gtcagcatag gtagtcaaca gcaggtgcat 292920 ttag aaagcggagg tgtggctttt acctagagga atgcctaata agtagtgtgg 292980 Page 194 715825 ‐ Sequence Listing.txt cagtcatact taaaggagac gtggaacatt tgaaaaccct atgtaggaga atcacaacaa 293040 tgattaaagt ttttaaaaat tatg aatttagaat aaaagaatta aaacttttag 293100 atacagaaat aaagaaaact gattaatgat gagcagaaag tatagagtat tattattctc 293160 aaatgggaaa tggctctatt tcat tgaaaacaga cagg gctatatgtt 293220 tgttaatgaa acaaccacaa gctacataga aaataaattt atatttctgt tata 293280 gaat ctcatgatac gcat taggatgaaa atttctatag caccattttc 293340 ctct agttaactga attcttgttt ccaaactatt tatg caattctggc 293400 cttaaaagta ctat acacccttaa gcttagtgta gtggcattta attcacttaa 293460 catatatttt ttaaactgcc ttttccttct gttactaaca aaaaagaagc tctaacttta 293520 tgttattttc ctgaatatgt cattgatatg aaattataga cactacaaga caaaaaatga 293580 ttttttctcc cccaccaatt ctttaaaatg cttataatat ctccctaggg gattttaata 293640 actttttaaa taagaaaaga ctatttcagc ataaagacct acattttaaa tggcaatgtt 293700 aaggtaaatt tcatctgtca tttttataaa aaagtggtta gcctctgcct ctgtggtaag 293760 aatactgggt accaactgca aagtagctgg caggtactca atcttaagga atgaaataga 293820 agttttacaa acaggttccc ctca tacaaagtat actaaaacct gaagatggga 293880 gcctcagtag tgatctttct gtcaatttta tgtatataat atacatgaga tatt 293940 atattttaat aatttaattt attgatataa atacgtatat ttatagctgt aaaatatatg 294000 ttatttgtgt ctaagaagtt tctgtcatga tttatcaata aaaactctgc cttcatcttt 294060 ttgataaatc ttcaatctgg aaactaagaa aatcaccaca cttaaaaaaa aatagaaaag 294120 aaaccgagtg ggcattattt aggtagtgtg ttaataagca acactttttt actgaagctg 294180 aaacctttat gatactccct ggacacatag taaa tgtt tgttttcata 294240 aaacacacat tgattttgaa ctatatgctg tttctttatt ttgaagtttt tttttaatgt 294300 gaggagattt gaaaagtgga cagagatgtt cataaaacag aaaaaaacta agtcgttgca 294360 ttctgtttca gtggttatca atca ctgactttat tagatgaata caaattatga 294420 attttttgtg aaaagggaaa gggaaatgta aactgtgctt caactattcg tgaa 294480 agcgaaatat tcttgtgtgt ttcagatttc tactttccat ggctcttaat tattatcttt 294540 Page 195 715825 ‐ Sequence Listing.txt ggaatatttg ggctaacagt gatgctattt gtattcttat tttctaaaca gtag 294600 gtgtggagta gtattctttg gtattttgta ccagttgttt agatttccat atgtgtttct 294660 atttgttatt tgatattttc tttgtcaaat tatgagtgga aattttagtt aacctagtac 294720 acttttatct ccagttatat atttaccatt catataaaac tcaatttgtt gtatttatct 294780 tagacaattt agaggtttag attctatctg tgta caggacatta agaggcttag 294840 gctggtgact atgcatacct tgtgatatgt acctctttat ccaagagcta gctctttccc 294900 cctc aacaagttga cccattcatt ccaggacttc aaagtatcac tgagcctttg 294960 gctgagtctg atacagtcct tatatacaga tttt ttttccttga gacggagtct 295020 tactctgttg cccaggctgg agtgcaatgg cgcaatcttg gctcactgca accgccgccc 295080 ttca agcaattctc ctgcctcagc ctccagagta gctgggatta caggcatgcg 295140 ccaccaagcc cagctaattt tgtattttta gatacagttt caccatgttg gtcagactgg 295200 tctcgaactc ctgacctcag gtgatctgcc cacctcagcc tcccaaagcg ctgggattac 295260 aggcgtgagc taccgcgcct ggccccattt tttt ccca atggttaatc 295320 ttgttgcttc tcctagaatt acta acactcccag gttgcctaga actctcctgg 295380 tttttagcaa tgcaagtccg cagg aaatccctca gttccaggta accaagacag 295440 ttgatcccct tacctagaat tgaaaatacg ttctccagct gaagccaaga ggcatctata 295500 aatcaaaatg agatctatgt taatatattt taaaagattt tactttgttt tgtaaggtag 295560 tatagcactt ttca aaacagaatt ttgttaggaa gaagaattat gcta 295620 gatttctata gtgtcaagca tgctaaaagt ctaactgaat gcagaaaggg ttattttcag 295680 tagagcttca tgtccaattt tataatataa accaattgga aagtaaaatt cattctgaat 295740 tccattttgc acctaacttt ctggcaacat tcctgttttc caaaaaagca gctatcataa 295800 atcacaacac ctat tgtttcagga aaataaataa tttt agaattttaa 295860 tttgtgtatt taagtaatgc caacaacaaa aaagccaaat tattctgttg attaatttca 295920 gtttattaat ctatatattt ggtgggaaaa cata acttcagtag ataaactcac 295980 gaggtatgta aagtaattag ctcttagtat tagctgtgaa tttctagcca ttgtgaaggc 296040 caagtcaatt tgttatgttg tttagttata aaca atattaggaa gaaaaaatta 296100 Page 196 715825 ‐ Sequence Listing.txt tcctctcaaa aagtaggatt tccaagaaaa catattactt ctaatacagt gctttttata 296160 aataatgaaa tgcttaacta taatgtttag tcaaaatcac ctac aattgatttg 296220 aaatctttat tgttctccca aatttcctgc ttga attttctgta aatt 296280 aactttattt tttatttgcc cattaaaaac gcttatcatt gtctaaattt gcatgttcta 296340 ctgaaagtgg gaaatagtag caaatatttg tcagcaagta tggacagaac atgtagttcc 296400 aacaattaaa ttgatactgc cgag atttttccta gaactgtagg gctgtaaagt 296460 ggcgtcaggt cctacatgcc tttgaaattt tctgagtcca caattcatta tccaacccac 296520 ttcaccctgc tttaatccag ttaattgagt caactctagc aaaatttata tttg 296580 tatctgatac aaaaccacaa acatagtttc aagtcaggct attattatac tggttcctac 296640 cacacaaccc tcccagcctt gtta ccaattgagg aaagaaataa cagc 296700 ctaaaataga atttccaaac cagtagcgaa attcagccta cagattcata ttttgttatt 296760 ttattttaat tagttttgat ttcagagtga agattttcct acaaagtgtt tgtaaaatag 296820 agaattttca cacaaaaatc cagatttggg gattatcttt taaaaaatga aagatgtagt 296880 gaaactaaac aaggcagcat atgctgcagc agacaaccag tatt tgggattggc 296940 tcacattctt taatttgcca ccatcctcat tcctcctaat gactttgcaa ctggcttgct 297000 ttattcctct gcatgacctg cttgggcctc ttagatttat gctctgccac tgtggcataa 297060 ggtcactaca accactagaa aaccactagc gcatgcctga atgcatcatc ctatttaaaa 297120 aggaaaagca acaa agtcaaacat cagccatttg gaaacctttg cttcctgtaa 297180 ttagaattat gttccatctt tttatgtttt tgggaatttg aaataccaat atgc 297240 agaatcaaaa aaaaaaaaac aaaacagcga aacagcagca tgacacaaag aacctgggtt 297300 tgga ttct ctgggtttga gccccaactg tgccaactat gaatgcatga 297360 tttgaacatg ttgcttaatt ttccaagttt ttgcacagat atatcatctg cctccctggg 297420 agtcataagg attaagtgaa atgtttagtg caggggtcac aaacttattt catagagtta 297480 gagtacattt ttaggctttt atac agtctctatc acagctactc aactctgcca 297540 ctgtagcacg aaagtggcca taaacaaaat ggaaatgaat gaagatgctt gtgttctcat 297600 aaaattttat ctacacaaac atgtgacagg ccagatttgg cccacagacc ttaatttagt 297660 Page 197 715825 ‐ Sequence Listing.txt gacccatagt ttagtgcaaa gtatatccca cagtgtctga tttatcagaa aaaa 297720 atgatagtag ttaa taatttgtat tacttatttc tatatctgta attcatcagt 297780 aacaatatgc tttaacattt gccccactga gtagtagagg ctacttaatg caatttataa 297840 aatggatttt tgcttattac ttggattagg taaaatagca agtggaaata ctgagaaaat 297900 gtactcctta tggaatggac tggactgacc attcacactg atag taactgatat 297960 ccaaaaatct ggttaccacc tcttcatgac agtgtcatct ctgaatagtc aggagttttt 298020 taaaaaatta aatgaattgt ttggaataat gcct ttttccagtg ctataatttg 298080 attttaaaaa ataaactcca ggccagatac aatggcttat agcatataaa tccagcactt 298140 tgggaggatg gggcgggagt attgccctga ggccaggagt tccagacagc tcgggcaatg 298200 actagagcaa atta caaaaaatga aacaacaaaa acac cctgtagtcc 298260 tagctactta ggaggctgag gcaagaatat gccc aggagtttga ggctgcagtg 298320 aattatgatt gcaccactgg actccagtgt gggcaatgaa gtaagaccct gtctcaaaaa 298380 gttttaaaaa aaattaaaaa caccataaat tccaattaca ctattaattg atag 298440 gatt tattcatttt tatgaccaaa aaataattta aagatttgga acaaaaaatg 298500 taagtgcatc ctagaattgt atatataaac ccatactgat tagttagaga tagttaaaat 298560 ttaatctgtc ccatctgaaa tgaaccctgt agtaaaaccc tggttaataa gatcatctta 298620 gataatttca taattaatat gaactatatg gctaacctac ccaagtctac cctttttcaa 298680 gggtgtaagt aatcttggct ccatgtggat tgactctttt ttctttcttt cctgtacaaa 298740 ttactgatga gatgtacact agaattgcct tatagctgaa atggaaatca gctttagatg 298800 aaattaaatt tctttctttc aaatactaaa tctggctgaa aataaaaagc aaaa 298860 aaacaattgt gggaaaacca cttt taatagactt cagatgaggc tttttgggtt 298920 ttttagttgt tctttttttt ccttctacag tttttctttc tcatttactg tctaatattt 298980 tcttctgttt ctcacactcc aattatataa agtaccagaa tatttggaaa aagtaatagt 299040 attgccaata ttttatttct tgct ataattgaga atatgtagct tttaagatgt 299100 caaaaccaaa attttatatg ttttcaagga ttaaaatgct gattctgccc ccagttccag 299160 ttccaaagat taaaggaatc gatccagatc aggt taat tttatctaaa 299220 Page 198 715825 ‐ Sequence g.txt ttgtagctag tactaattaa cacctgaaga ctcctgtcat atgttgaagg ttttctgtaa 299280 gctatatata tcacattcaa ttttcttgtg tctcttctcc tggagaaaat ttttttaaat 299340 attctatttc ttaaaaataa gaaaacgtca tatgtattta taca cactaattta 299400 ttta tatgttttgt tactgttgtt cttattgtaa ccataattaa tctctgaaca 299460 ttatttgcta attcatttaa ttattatgag tttcttttca tagatcttca ttttctttct 299520 attttctagg aaggaaaatt agaggaggtg aacacaatct tagccattca tgatagctat 299580 aaacccgaat tccacagtga tgactcttgg gttgaattta ttgagctaga tattgatgag 299640 ccagatgaaa agactgagga atcagacaca gacagacttc gtga ccatgagaaa 299700 tcacatagta gggt gaaggatggc gactctggac gtaccagctg ttgtgaacct 299760 gacattctgg agactgattt caatgccaat gacatacatg agggtacctc tgct 299820 cagccacaga ggttaaaagg agat ctcttatgcc ttgaccagaa gaatcaaaat 299880 aactcacctt atcatgatgc ttgccctgct cagc ccagtgttat ccaagcagag 299940 aaaaacaaac cacaaccact tcctactgaa ggagctgagt caactcacca agctgcccat 300000 attcagctaa gcaatccaag ttcactgtca aacatcgact tttatgccca ggtgagcgac 300060 attacaccag caggtagtgt ggtcctttcc ccgggccaaa agaataaggc gtcc 300120 caatgtgaca tgcacccgga aatggtctca ctctgccaag aaaacttcct tatggacaat 300180 gcctacttct gtgaggcaga tgccaaaaag tgcatccctg tggctcctca catcaaggtt 300240 gaatcacaca caag ccaa gaggacattt acatcaccac agaaagcctt 300300 accactgctg ctgggaggcc tgggacagga gaacatgttc caggttctga gatgcctgtc 300360 ccagactata cctccattca tatagtacag tccccacagg gcctcatact gact 300420 gccttgccct tgcctgacaa agagtttctc tgtg gctatgtgag ccaa 300480 ctgaacaaaa tcatgcctta gcctttcttt ggtttcccaa gagctacgta tttaatagca 300540 tgac tggggcaata acgtttaagc caaaacaatg tttaaacctt ttttggggga 300600 gtgacaggat ggggtatgga ttctaaaatg ccttttccca aaatgttgaa atatgatgtt 300660 aaaaaaataa gaagaatgct taatcagata gatattccta ttgtgcaatg taaatatttt 300720 aaagaattgt gtcagactgt ttagtagcag tgattgtctt aatattgtgg gtgttaattt 300780 Page 199 715825 ‐ Sequence Listing.txt ttgatactaa gcattgaatg gctatgtttt taatgtatag taaatcacgc tttttgaaaa 300840 agcgaaaaaa tcaggtggct gttc aggaaaattg aatgcaaacc atagcacagg 300900 ctaatttttt gttgtttctt aaataagaaa cttttttatt taaaaaacta aaaactagag 300960 gtgagaaatt taaactataa gcaagaaggc aaaaatagtt tggatatgta aaacatttat 301020 tttgacataa agttgataaa gattttttaa agac ttcaagcatg gctattttat 301080 ctac acactgtgta ctgcagttgg tatgacccct ctaaggagtg ctac 301140 agtctaaagc tggtttaatg ttttggccaa tgcacctaaa gaaaaacaaa ctcgtttttt 301200 acaaagccct tttatacctc cccagactcc ttcaacaatt ctaaaatgat tgtagtaatc 301260 tgcattattg gaatataatt gttttatctg aatttttaaa caagtatttg ttaatttaga 301320 aaactttaaa gcac agatcaactt accaggcacc aaaagaagta aaagcaaaaa 301380 agaaaacctt tcttcaccaa atcttggttg atgccaaaaa aaaatacatg ctaagagaag 301440 tagaaatcat agctggttca cactgaccaa gatacttaag tgctgcaatt gcacgcggag 301500 tgagtttttt agtgcgtgca gatggtgaga gataagatct atagcctctg cagcggaatc 301560 tgttcacacc caacttggtt ttgctacata attatccagg aagggaataa agaa 301620 tgta agttgaagca atga ctgg gtaatgaaac aaagagttca 301680 agaaataagt ttttgtttca cagcctataa ccagacacat actcattttt catgataatg 301740 aacagaacat agacagaaga aacaaggttt ccca cagataactg attt 301800 aaaccgctaa aagaaacttt ctttctcact aaatctttta taggatttat ttaaaatagc 301860 aaaagaagaa gtttcatcat tttttacttc ctctctgagt ggactggcct caaagcaagc 301920 attcagaaga aaaagaagca gtaa tttagaaatc attttgcaat cccttaatat 301980 cctaaacatc attcattttt gttgttgttg ttgttgttga gacagagtct cgctctgtcg 302040 taga gtgcggtggc gcgatcttga ctcactgcaa tctccacctc ccacaggttc 302100 aggcgattcc cgtgcctcag cctcctgagt gact acaggcacgc accaccatgc 302160 caggctaatt tttttgtatt ttagcagaga cggggtttca ccatgttggc caggatggtc 302220 tcgatctcct gacctcgtga tccacccgac tcggcctccc aaagtgctgg gattacaggt 302280 cacc gtgcccagcc ctaaacatca ttcttgagag cattgggata tctcctgaaa 302340 Page 200 715825 ‐ ce Listing.txt aggtttatga aaaagaagaa tctcatctca gtgaagaata cttctcattt tttaaaaaag 302400 cttaaaactt tgaagttagc tttaacttaa atagtatttc ccatttatcg cagacctttt 302460 ttaggaagca agcttaatgg ctgataattt taaattctct ctcttgcagg aaggactatg 302520 aaaagctaga attgagtgtt taaagttcaa catgttattt gtaatagatg tttgatagat 302580 tttctgctac tttgctgcta tggttttctc caagagctac ataatttagt ttcatataaa 302640 gtatcatcag tgtagaacct aattcaattc aaagctgtgt aaga ctatcttact 302700 atttcacaac agcctgacaa catttctata aata gctaaatacc tcaatcagtc 302760 tcagaatgtc attttggtac tttggtggcc acataagcca ttattcacta gtatgactag 302820 ttgtgtctgg atat ttaactctct ttatgtctgt tttc cttcaaagtt 302880 taataaattt ttgg attcctgata gtgtgcttct gttatcaaac accaacataa 302940 aaatgatcta aaccactctg tatactgtga attatcattg gagc ccac 303000 tggatcaaat acatcagcat tgggtatgga gatttttatg tgctgagata tagagaggga 303060 aacatatccc ccttccctta ttttttgaga agacaaaagc caga aatatcccac 303120 ggcc ctccccttag gctgtgactc cccataggca aaggttcata gagctgtgta 303180 gcat catggaaaat aaatgacatg ggat gagggagagt gatatgtgag 303240 cattatcttt acatttccag cttgagcatg ttgtctggaa ggaaggaaag cagctcttcc 303300 tctgccattc acccattggc ctaagtcagt gact agctgcttgt tatcatggga 303360 atcagctaat aagtcaggct tgggaggaag gctgattagg taagttgtgt aggagcctga 303420 gagagccatg aagtttagat tcctacagca ggaggcagga tgcaggtgag gctg 303480 aaccctaggc tcctgagcag gcactggatt ctgagatgta ggaatctggt gaggacattg 303540 ataaacctac taaacaatga cgtattgctt cagcaagtca aatgcaaagt gccacaactt 303600 tttataatac gtta tgttaaaaaa aaaaaatgtc ttcacctgct gccctctgcc 303660 ctgtgagcag ccattacctg aaagaaccat ggagtgaagc ctcagggctt cttcatatag 303720 atgctttaag atatgaggag tacagggaaa agaaagcctg cctacttcca tggattgaaa 303780 taacacaatt ctatttcaga agattaatgg tgtgttgaaa atggctacac acatctttca 303840 gcatttcaat ttctcaaagt ttctactaac actttattca agtgctataa tatttacata 303900 Page 201 715825 ‐ Sequence Listing.txt tttacatatt tgtataccaa aatatgtctt gttatgtgct tgttttaggg atag 303960 tgaccagaaa aaccagaagt tacttaaatc taaacttttt agtttggaat ccaagatccc 304020 acataatttg ccccagtctc ctttgagagt ttaaaattta agacctagat ggca 304080 cagcttctga ataagaattt gatgtttggt taacattcaa actctattgc tgtggaaatc 304140 taatgagcat atgatgtcag ctatgttaca cgggaaacat tagt ttaaatgatc 304200 tctgactgat aaatgacatc ggga gaaactataa ccacctggag ataagttata 304260 actt gagtgtagtg acttgtaatt ttcc cctatagaaa ctctggaagc 304320 tatgtttctg gagatgtaac aagagtaact ggctccagtg aggcatagag cttctaagcc 304380 tgggagactc ctttacctgc ccaatacctt ctctgaatct gagctgccag ttgtaggagg 304440 agaggaagga aaagaccttc tggatagcta tataaacagc tgtttagatt gcttcatgca 304500 ctgttatcat tactgtgact ctaaagcaga aagcctgatg ctgtatccct tctgtcctac 304560 ctga gtagactgga accaagtatg gtgaatctgg ggaatgtgtg gttgagccta 304620 agaagatccc cttgcatatg tagcaaaaga cacttgccat ttcttgaaca aagtttgtgc 304680 tttcccatct ctatgttctt gcct cctccttcaa ctaaaaagct cccacttacc 304740 aaccctgcct gtcaagattc ccttcatcct ccca gctctaatgc ctccttcatg 304800 aactctcctc tgattcccac catccaatca gtgatttttt cttctgaacc atgtttaatg 304860 gtgtttatca cattactttg gtagctcacc tgacaaacgg c 304901 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 6 tcagggcatt ctttccattc 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence Page 202 715825 ‐ Sequence Listing.txt <220> <223> oligonucleotide <400> 7 cataatcagg gcattctttc 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 8 cctttaatct ttggaactgg 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 9 tcatcaatat ctagctcaat 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 10 cttagaagtc tgtctgtgtc 20 <210> 11 <211> 20 <212> DNA <213> cial Sequence <220> <223> oligonucleotide <400> 11 Page 203 715825 ‐ Sequence Listing.txt cctgctggtg taatgtcgct 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 12 atgtaaatgt ggtt 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 13 tggtgatgta aatgtcctct 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 14 ttctgtggtg atgtaaatgt 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 15 aggctttctg tggtgatgta 20 <210> 16 Page 204 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 16 tggtaaggct ttctgtggtg 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 17 agttggtctg tgctcacata 20 <210> 18 <211> 20 <212> DNA <213> Artificial ce <220> <223> oligonucleotide <400> 18 gttg gtctgtgctc 20 <210> 19 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oliognucleotide <400> 19 gcatgatttt gttcagttgg 20 <210> 20 <211> 20 <212> DNA <213> Artificial Sequence Page 205 715825 ‐ Sequence Listing.txt <220> <223> oligonucleotide <400> 20 tataaaaggg ctttgtaaaa 20 <210> 21 <211> 20 <212> DNA <213> Artificial ce <220> <223> oligonucleotide <400> 21 catagcagca aagtagcaga 20 <210> 22 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 22 gctatttttg gctatagaaa 20 <210> 23 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 23 gattgaggta tttagctatt 20 <210> 24 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 24 Page 206 715825 ‐ ce Listing.txt gatccatacc acct 20 <210> 25 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 25 ccagagatcc atacctgtag 20 <210> 26 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 26 tgctaaggat agctgctgtg 20 <210> 27 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 27 ttgtctttag gcctggatta 20 <210> 28 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 28 ttagaagaat ttgtctttag 20 <210> 29 Page 207 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 29 gtgaatttag gctccttaga 20 <210> 30 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 30 gctgtatggg tcctaggttc 20 <210> 31 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 31 taacagctgt tttccccagc 20 <210> 32 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 32 ccac tgtaccacca 20 <210> 33 <211> 20 <212> DNA <213> Artificial Sequence Page 208 715825 ‐ Sequence Listing.txt <220> <223> oligonucleotide <400> 33 ttgcactatt tcatcaacag 20 <210> 34 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 34 gggtggatct ggttgcacta 20 <210> 35 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 35 attgcgtggt gcttcccatc 20 <210> 36 <211> 20 <212> DNA <213> cial Sequence <220> <223> oligonucleotide <400> 36 tagggtccat cattttccat 20 <210> 37 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 37 Page 209 715825 ‐ Sequence Listing.txt caatgagtac actggaactg 20 <210> 38 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 38 aactcgccat aatttccaga 20 <210> 39 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 39 agcccaaata ttccaaagat 20 <210> 40 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 40 tcagcatttt aatcctttgc 20 <210> 41 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 41 attttccttc cttgaggaga 20 <210> 42 Page 210 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 42 agattgtgtt cacctcctct 20 <210> 43 <211> 20 <212> DNA <213> Artificial ce <220> <223> oligonucleotide <400> 43 aacccaagag tcatcactgt 20 <210> 44 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 44 ctggctcatc aatatctagc 20 <210> 45 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 45 tgtgtctgat tcctcagtct 20 <210> 46 <211> 20 <212> DNA <213> Artificial Sequence Page 211 715825 ‐ Sequence Listing.txt <220> <223> oligonucleotide <400> 46 tatgtcattg gcattgaaat 20 <210> 47 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 47 aaggcataag agatctgctt 20 <210> 48 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 48 actcagctcc ttcagtagga 20 <210> 49 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 49 ccct gccttattct 20 <210> 50 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 50 Page 212 715825 ‐ ce Listing.txt ggcattgtcc ataaggaagt 20 <210> 51 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 51 actttttggc atctgcctca 20 <210> 52 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 52 gatgcacttt ttggcatctg 20 <210> 53 <211> 20 <212> DNA <213> Artificial ce <220> <223> oligonucleotide <400> 53 cagtcgcatt gagtatgagg 20 <210> 54 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 54 ctctttgtca ggcaagggca 20 <210> 55 Page 213 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 55 gtgctcacat agccacatga 20 <210> 56 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 56 aagaaaggct aaggcatgat 20 <210> 57 <211> 20 <212> DNA <213> Artificial ce <220> <223> oligonucleotide <400> 57 aaatacgtag ctcttgggaa 20 <210> 58 <211> 20 <212> DNA <213> cial Sequence <220> <223> oligonucleotide <400> 58 caatcactgc tactaaacag 20 <210> 59 <211> 20 <212> DNA <213> Artificial Sequence Page 214 715825 ‐ Sequence g.txt <220> <223> oligonucleotide <400> 59 aaacatagcc attcaatgct 20 <210> 60 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 60 gtgctatggt ttgcattcaa 20 <210> 61 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 61 cata tccaaactat 20 <210> 62 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 62 catcaaccaa gatttggtga 20 <210> 63 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 63 Page 215 715825 ‐ Sequence Listing.txt gaggctatag atcttatctc 20 <210> 64 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 64 tagtgagaaa gaaagtttct 20 <210> 65 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 65 aatgctctca agaatgatgt 20 <210> 66 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 66 acactcaatt ctagcttttc 20 <210> 67 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 67 catctattac aaataacatg 20 <210> 68 Page 216 715825 ‐ Sequence g.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 68 ctcttggaga aaaccatagc 20 <210> 69 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 69 tctacactga ttta 20 <210> 70 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 70 cacagctttg aattgaatta 20 <210> 71 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 71 agtcttccaa acacacagct 20 <210> 72 <211> 20 <212> DNA <213> Artificial Sequence Page 217 715825 ‐ Sequence Listing.txt <220> <223> oligonucleotide <400> 72 aggctgttgt gaaatagtaa 20 <210> 73 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 73 atgt tgtcaggctg 20 <210> 74 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ucleotide <400> 74 ccaaaatgac attctgagac 20 <210> 75 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 75 ataatggctt atgtggccac 20 <210> 76 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 76 Page 218 715825 ‐ Sequence g.txt agttatgtga ccctgattga 20 <210> 77 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 77 ttgagtgttc ctaaaatgaa 20 <210> 78 <211> 20 <212> DNA <213> cial Sequence <220> <223> oligonucleotide <400> 78 atggaggctg gaggttcaaa 20 <210> 79 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 79 tagggtccat ctttcaagac 20 <210> 80 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 80 tctccagata gaatctaaac 20 <210> 81 Page 219 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 81 tccaaatatt ctggtacttt 20 <210> 82 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 82 tattagttac cttgaggaga 20 <210> 83 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> oligonucleotide <400> 83 attttccttc ctagaaaata 20 <210> 84 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 84 aaag ctga 20 <210> 85 <211> 20 <212> DNA <213> Artificial Sequence Page 220 715825 ‐ Sequence Listing.txt <220> <223> target sequence <400> 85 gaaagaatgc cctgattatg 20 <210> 86 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target ce <400> 86 ccagttccaa agattaaagg 20 <210> 87 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 87 attgagctag atattgatga 20 <210> 88 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target ce <400> 88 gacacagaca gacttctaag 20 <210> 89 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 89 Page 221 715825 ‐ Sequence Listing.txt agcgacatta caccagcagg 20 <210> 90 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 90 aaccaagagg acatttacat 20 <210> 91 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 91 agaggacatt tacatcacca 20 <210> 92 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 92 acatttacat agaa 20 <210> 93 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target ce <400> 93 tacatcacca cagaaagcct 20 <210> 94 Page 222 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 94 caccacagaa agccttacca 20 <210> 95 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 95 tatgtgagca aact 20 <210> 96 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 96 gagcacagac caactgaaca 20 <210> 97 <211> 20 <212> DNA <213> Artificial ce <220> <223> target sequence <400> 97 ccaactgaac aaaatcatgc 20 <210> 98 <211> 20 <212> DNA <213> Artificial Sequence Page 223 715825 ‐ Sequence Listing.txt <220> <223> target sequence <400> 98 tctgctactt tgctgctatg 20 <210> 99 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 99 tttctatagc caaaaatagc 20 <210> 100 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 100 aatagctaaa tacctcaatc 20 <210> 101 <211> 20 <212> DNA <213> Artificial ce <220> <223> target sequence <400> 101 aggtcctaca ggtatggatc 20 <210> 102 <211> 20 <212> DNA <213> cial Sequence <220> <223> target sequence <400> 102 Page 224 715825 ‐ Sequence Listing.txt ctacaggtat ggatctctgg 20 <210> 103 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 103 cacagcagct atccttagca 20 <210> 104 <211> 20 <212> DNA <213> cial Sequence <220> <223> target sequence <400> 104 taatccaggc ctaaagacaa 20 <210> 105 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 105 tctaaggagc tcac 20 <210> 106 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 106 gaacctagga cccatacagc 20 <210> 107 Page 225 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 107 gctggggaaa gtta 20 <210> 108 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 108 tggtggtaca gtggatgaaa 20 <210> 109 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 109 ctgttgatga aatagtgcaa 20 <210> 110 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 110 tagtgcaacc agatccaccc 20 <210> 111 <211> 20 <212> DNA <213> Artificial Sequence Page 226 715825 ‐ Sequence Listing.txt <220> <223> target sequence <400> 111 aagc accacgcaat 20 <210> 112 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 112 atggaaaatg atggacccta 20 <210> 113 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 113 cagttccagt gtactcattg 20 <210> 114 <211> 20 <212> DNA <213> Artificial ce <220> <223> target sequence <400> 114 tctggaaatt atggcgagtt 20 <210> 115 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 115 Page 227 715825 ‐ Sequence Listing.txt atctttggaa tatttgggct 20 <210> 116 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 116 gcaaaggatt ctga 20 <210> 117 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 117 tctcctcaag gaaggaaaat 20 <210> 118 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 118 agaggaggtg aacacaatct 20 <210> 119 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target ce <400> 119 acagtgatga ctcttgggtt 20 <210> 120 Page 228 715825 ‐ Sequence Listing.txt <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 120 gctagatatt gatgagccag 20 <210> 121 <400> 121 <210> 122 <211> 20 <212> DNA <213> Artificial ce <220> <223> target sequence <400> 122 atgc caatgacata 20 <210> 123 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 123 aagcagatct cttatgcctt 20 <210> 124 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 124 tcctactgaa ggagctgagt 20 Page 229 715825 ‐ Sequence Listing.txt <210> 125 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 125 agaataaggc gtcc 20 <210> 126 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 126 acttccttat ggacaatgcc 20 <210> 127 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 127 tgaggcagat gccaaaaagt 20 <210> 128 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 128 cagatgccaa catc 20 <210> 129 <211> 20 <212> DNA <213> Artificial Sequence Page 230 715825 ‐ Sequence Listing.txt <220> <223> target sequence <400> 129 cctcatactc aatgcgactg 20 <210> 130 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 130 tgcccttgcc tgacaaagag 20 <210> 131 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 131 tcatgtggct atgtgagcac 20 <210> 132 <400> 132 <210> 133 <211> 20 <212> DNA <213> cial Sequence <220> <223> target sequence <400> 133 agag ctacgtattt 20 <210> 134 <211> 20 <212> DNA Page 231 715825 ‐ Sequence Listing.txt <213> Artificial Sequence <220> <223> target sequence <400> 134 ctgtttagta attg 20 <210> 135 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 135 ttgaatgcaa accatagcac 20 <210> 136 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 136 atagtttgga tatgtaaaac 20 <210> 137 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target ce <400> 137 tcaccaaatc ttggttgatg 20 <210> 138 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence Page 232 715825 ‐ ce Listing.txt <400> 138 gagataagat ctatagcctc 20 <210> 139 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 139 agaaactttc tttctcacta 20 <210> 140 <211> 20 <212> DNA <213> Artificial ce <220> <223> target sequence <400> 140 acatcattct tgagagcatt 20 <210> 141 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 141 gaaaagctag aattgagtgt 20 <210> 142 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 142 gctatggttt tctccaagag 20 Page 233 715825 ‐ Sequence Listing.txt <210> 143 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 143 taaagtatca tcagtgtaga 20 <210> 144 <211> 20 <212> DNA <213> cial Sequence <220> <223> target sequence <400> 144 taattcaatt caaagctgtg 20 <210> 145 <211> 20 <212> DNA <213> Artificial ce <220> <223> target sequence <400> 145 agctgtgtgt ttggaagact 20 <210> 146 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 146 ttactatttc acaacagcct 20 <210> 147 <211> 20 <212> DNA Page 234 715825 ‐ Sequence Listing.txt <213> cial Sequence <220> <223> target sequence <400> 147 gaca acatttctat 20 <210> 148 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 148 gtctcagaat gtcattttgg 20 <210> 149 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 149 gtggccacat aagccattat 20 <210> 150 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 150 tcaatcaggg tcacataact 20 <210> 151 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence Page 235 715825 ‐ Sequence Listing.txt <400> 151 tttgaacctc cagcctccat 20 <210> 152 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 152 gtcttgaaag atggacccta 20 <210> 153 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target ce <400> 153 gtttagattc tatctggaga 20 <210> 154 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> target sequence <400> 154 aaagtaccag aatatttgga 20 Page 236