TW201042039A - Improved anti-serum albumin binding variants - Google Patents

Improved anti-serum albumin binding variants Download PDF

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TW201042039A
TW201042039A TW099105020A TW99105020A TW201042039A TW 201042039 A TW201042039 A TW 201042039A TW 099105020 A TW099105020 A TW 099105020A TW 99105020 A TW99105020 A TW 99105020A TW 201042039 A TW201042039 A TW 201042039A
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Angelis Elena De
Carolyn Enever
Hai-Qun Liu
Oliver Schon
Christopher Plummer
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Glaxo Group Ltd
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Description

201042039 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種抗血清白蛋白免疫球蛋白單一可變域 DOM7h-l 1之經改良變體，以及包含此等變體之配位體及 藥物接合物（drug conjugate)，組合物、核酸、載體及宿 主。 【先前技術】 WO 04003019及W0 2008/096158揭示具有治療學上適用 〇 之半衰期的抗血清白蛋白（SA)結合部分，諸如抗SA免疫球 蛋白單一可變域（dAb)。此等文獻揭示單體抗SA dAb以及 包含此等dAb之多特異性配位體，例如包含抗SA dAb及特 異性結合目標抗原（諸如TNFR1)之dAb的配位體。揭示特 異性結合來自一種以上物種之血清白蛋白的結合部分，例 如人類/小鼠交叉反應性抗SA dAb。 W0 05118642及WO 2006/059106揭示將抗SA結合部分 (諸如抗SA免疫球蛋白單一可變域）與藥物接合或締合以增 〇 加藥物半衰期之構想。揭示及例示蛋白質、肽及NCE(新 穎化學實體）藥物。W0 2006/059106揭示使用此構想來增 加促胰島素劑之半衰期，該等促胰島素劑例如為腸促胰液 素（incretin)激素，諸如升糖素樣肽（GLP)-l。 亦參考 Holt等人，「Anti-Serum albumin domain antibodies for extending the half-lives of short lived drugs」，Protein Engineering, Design & Selection，第 21卷，第 5號，第 283-288頁 » 2008 - 146451.doc 201042039 WO 2008/096158揭示DOM7h-ll，其為良好的抗SA dAb。需要提供改良之dAb，其為DOM7h-ll之變體且特異 性結合血清白蛋白，較佳來自人類及非人類物種之白蛋 白，其將在疾病之動物模型中以及對於人類療法及/或診 斷提供效用。亦需要在相對適度與高親和力抗SA結合部分 (dAb)之間提供選擇。此等部分可連接於藥物，抗SA結合 部分係根據所預期之終端應用來選擇。視抗S A結合部分之 選擇而定，此將允許藥物更適用於治療及/或預防慢性或 急性適應症。亦需要提供為單體或在溶液中實質上為單體 之抗dAb。當出於拮抗受體之目的，將抗SA dAb連接於結 合部分，例如特異性結合細胞表面受體（諸如TNFR1)之 dAb時，此將尤其有利。抗SA dAb之單體狀態適用於減少 受體交聯之機會，因為不太可能形成會結合及交聯細胞表 面上之受體（例如TNFR1)從而提高受體促效作用及有害受 體信號傳導之可能性的多聚體。 【發明内容】 本發明之態樣解決此等問題。 為此目的，本發明之發明者令人驚言牙地發現可以 DOM7h-ll之FW2/CDR2接合點（位置49至51，根據Kabat編 號）為目標進行有益突變。 因此在一個態樣中，本發明提供DOM7h-11之抗血清白 蛋白（SA)免疫球蛋白單一可變域變體，其中該變體與 DOM7h-11相比在F W2/CDR2接合點（位置49至5 1，根據 Kabat編號）中包含至少一個突變，且其中該變體與 146451.doc 201042039 DOM7h-ll之胺基酸序列相比具有2至8個變化。 在一個態樣中，本發明提供D〇M7h_U2抗血清白蛋白 (SA)免疫球蛋白單一可變域變體，其中該變體與議π· 11相比在位置32(根據Kabat編號）包含Met，且其中該變體 與DOM7h-ll之胺基酸序列相比具有〇至4個其他變化。 Ο ❹ 本發明之任-態樣的實施例提供具有良好抗血清白蛋白 親和力之D〇M7h-U變體。變體之選擇可允許根據所需治 療及/或預防環境來調整半衰期。舉例而言，在一個實施 例中，變體對於血清白蛋白之親和力相對較高，使得變體 將適用於包括於在治療及/或預防慢性或持續性疾病、病 狀、中毒或其他慢性適應症中有用之產物中。在一個實施 例中’變體對於血清白蛋白之親和力相對適度，使得^體 將適用於包括於在治療及/或預防急性疾病、病狀、中毒 或其他急性適應症中有用之產物中。在一個實施例中，變 體對於A清白蛋白之親和力為中度，使得變體將適用於包 括於在治療及/或預防急性或慢性疾病、病狀、中毒或其 他急性或慢性適應症中有用之產物中。 可設想對血清白蛋白具有適當高親和力及特異性之分子 將保持於循環中足夠久以具有所需治療作用（Win· w⑽細⑽w似22, 521_522 (2004))。在此處，高親 和力抗SA變體將保持於匹配物種之血清白蛋白之血清循環 的血清循環中（购厕_158)…旦處於循環中， 變體（AlbudAb為抗血清白蛋白⑽或免疫球蛋 白單一可變域）之任何融合治療劑’不管為刪、狀或蛋 146451.doc 201042039 白質’隨後均將能夠作用於其目標更長時間且顯示更久持 續治療作用。此將允許乾向慢性或持續性疾病而 够 給藥。 貝繁 具有中度親和力（但對S A具有特異性）之變體將僅於血清 循環中保持較短時間（例如幾小時或幾天），從而允許融人 治療劑特異性靶向與急性疾病有關之治療目標。 ° 此方式可藉由選擇具有適當白蛋白結合親和力及/戍血 清半衰期之抗SA變體而使含抗SA之產物適於治療疾病領 域。 本發明之一態樣提供包含任何如上所述之抗S a變體及特 異性結合除S A以外之目標抗原之結合部分的多特異性配位 體。 本發明之一態樣提供一種融合產物，例如融合蛋白或與 肽或NCE(新穎化學實體）藥物之融合物，其包含多肽、蛋 白質、肽或NCE藥物融合或接合（對於NCE)於任何如上所 述之變體，其中該變體為DOM7h-ll-15或DOM7h-ll-15S12P(或具有與DOM7h-l 1-15之胺基酸序列至少95%、 96%、97°/。、98%或99% —致之胺基酸的變體）或D〇M7h- 11-12(或具有與DOM7h-l 1-12之胺基酸序列至少95。/0、 96%、97%、98%或99% —致之胺基酸的變體）。DOM7h-11-15及001^711-11-12當融合或接合於搭配物時親和力僅適 度降低，使得其適用於融合產物。DOM7h-ll-15sl2PS與 DOM7h-ll-15相同，除了位置12(根據Kabat編號）為脯胺酸 以替代絲胺酸以外。此提供WO 08052933中闡述之優勢， 146451.doc 201042039 包括降低對含有此域抗體之融合蛋白之蛋白質_L的纟士人且 利於純化。WO 08052933之全部揭示内容係以引用的方式 併入本文中。類似地，本發明提供如本文所揭示之 DOM7h-ll變體，其中該變體包含下文闡述之胺基酸序 列’除了位置12(根據Kabat編號）為脯胺酸以外。本發明亦 提供包含此等DOM7h-ll變體之融合蛋白、接合物或組合 物。 本發明之一個態樣提供DOM7h-ll.之變體，其包含與
〇 DOM7h-l 1-153121>之胺基酸序列一致或與 D〇M7h-l 1-15S12P 之胺基酸序列相比具有至多4個變化的胺基酸序列，限制 條件為變體之胺基酸序列在FW2/CDR2接合點（位置49至 5 1，根據Kabat編號）中具有至少一個突變。 本發明之一態樣提供一種組合物，其包含任何前述態樣 之變體、融合蛋白或配位體，及醫藥學上可接受之稀釋 劑、載劑、賦形劑或媒劑。 Q 本發明之一態樣提供一種治療或預防患者之疾病或病症 之方法，其包含投與該患者至少一劑本發明之任何態樣或 實施例之變體。 本發明之一鉍樣提供一種多肽融合物或接合物，其包含 如本文揭不之抗血清白蛋白dAb(例如D〇M7h-U-15或 001^1711-11-3或00^[7]1-11-153121>或與00^[711-11-153121>之胺 基酸序列相比具有至多4個變化之及腸促 胰液素或促胰島素劑，例如腸促胰島素類似物_4(exendin_ 4)、GLP-l(7-37)、GLP-l(6-36)或 WO 06/059106 中揭示之 146451.doc 201042039 任何腸促胰液素或促胰島素劑，此等藥劑係以引用的方式 明確併入本文中，仿佛書寫於本文中以便包括於本發明及 下文申請專利範圍中一般。 【實施方式】 在本說明書中，已參考實施例以使說明書能清楚及簡明 書寫之方式描述了本發明。希望且應瞭解實施例可在不脫 離本發明之情況下以不同方式組合或分離。 除非另外定義，否則在本文中使用之技術及科學術語具 有與此項技術（例如細胞培養、分子遺傳學、核酸化學、 〇 雜交技術及生物化學）中一般技術者通常所瞭解相同之含 義。對於分子、遺傳及生化方法（一般參看Sambrook等人， Molecular Cloning: A Laboratory Manual，第 2 版（1989)
Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.及 Ausubel 等人，Short Protocols in Molecular Biology (1999)第 4版，John Wiley & Sons, Inc.，其係以引用的方 式併入本文中）及化學方法使用標準技術。 〇 如本文中所用，術語「腫瘤壞死因子受體l(TNFRl)之拮 U 抗劑」或「抗TNFR1拮抗劑」或其類似術語係指結合 TNFR1且可抑制TNFR1之一種（亦即一或多種）功能的藥劑 (例如分子、化合物）。舉例而言，TNFR1之括抗劑可抑制 TNFa與TNFR1之結合及/或抑制經由TNFR1介導之信號轉 導。因此，TNFR1介導之過程及細胞反應（例如在標準 L929細胞毒性檢定中TNFa誘導之細胞死亡）可用TNFR1之 拮抗劑來抑制。 146451.doc 201042039 「患者」為任何動物，例如哺乳動物，例如非人類靈長 類動物（諸如狒狒、值河猴或獼猴）、小鼠、人類、兔、大 鼠、狗、猶或豬。在-個實施例中，患者為人類。 如本文中所用，「狀」係指約2至約5〇個經由狀鍵聯接在 一起之胺基酸。 如本文中所用，「多肽」係指至少約50個藉由肽鍵聯接 在-起之胺基酸。多肽-般包含三級結構且摺疊成功能 域。 如本文令所用，抗體係指IgG、IgM、IgA、IgD或IgE或 片段（諸如Fab、F(ab’）2、Fv、二硫鍵連接之Fv、scFv、閉 &構1夕特異性抗體、二硫鍵連接之scpv、雙功能抗 體），而不管是來源於任何天然產生抗體之物種或是藉由 重組DNA技術產生；不管是自血清、B細胞、融合瘤、轉 染瘤、酵母或是自細菌分離。 如本文中所用，「抗體型式（antib〇dy f〇rmat)」係指任何 適合多肽結構，其中可併有一或多個抗體可變域以便在結 構上賦予對抗原之結合特異性。在此項技術中已知多種適 合抗體型式’諸如敌合抗體、人類化抗體、人類抗體、單 鏈抗體、雙特異性抗體、抗體重鏈、抗體輕鏈、抗體重鏈 及/或輕鏈之均二聚體及雜二聚體、任何前述抗體之抗原 結合片段（例如Fv片段（例如單鍵Fv(scFv)、二硫鍵結之 Fv)、Fab片段、Fab·片段、F(ab’)2片段）、單一抗體可變域 (例如dAb、、Vhh、Vl)及任何前述抗體之經修飾型式 (例如藉由共價連接聚乙二醇或其他適合聚合物或人類化 146451.doc 201042039
Vhh而修飾）。 月5吾「免疫球蛋白單一可傲代 ’艾或」係指獨立於不同v區或 v域、特異性結合抗原或抗眉決 乂机原决疋基之抗體可變域（vH、 VHH、vL)。免疫球蛋白單—可變域可與其他可變區或可變 域一起存在於一種構型（例如同多聚體或雜多聚體）中，其 中該其他區或域不為單一免疫球蛋白可變域與抗原結合所 需(亦即其中免疫球蛋白單-可變域結合抗原獨立於其他 可變域)。當用於本文中時’術語「域抗體」或「dAb」盥 「免疫球蛋白單—可變域」相同。當用於本文中時，術語 「單-免疫球蛋白可變域」肖「免疫球蛋白單一可變域」 相同。當用於本文中時，術語「單—抗體可變域」或「抗 體單-可變域」與「免疫球蛋白單一可變域」才目同。在一 個實施例中，免疫球蛋白單—可變域為人類抗體可變域， 但亦包括其他物種之單一抗體可變域，諸如齧齒動物⑼ 如WO 00/29004中所揭示，該案之内容係以全文引用的方 式併入本文中）、護士 t (nurse shark)及駱駝Vhh dAk。駱 乾VHH為來源於包括路騎、路馬、羊乾、單峰路乾及原駝 之物種天然產生之無輕鏈之重鏈抗體的免疫球蛋白單一可 變域多肽。該vHH可經人類化。 「域」為具有三級結構的摺疊蛋白質結構，獨立於該蛋 白質之其餘部分。一般而言’域負責蛋白質之個別功能特 性，且在許多情況下可添加、移除或轉移至其他蛋白質而 不會損失該蛋白質之其餘部分及/或該域的功能。「單一抗 體可變域」為包含抗體可變域特有序列的摺疊多肽域。因 146451.doc •10· 201042039 此，其包括完整抗體可變域及經修飾之可變域（例如其中 一或多個環已經被不為抗體可變域所特有之序列置換）， 或已截短或包含N端或C端延伸之抗體可變域，以及至少 保留全長域之結合活性及特異性之可變域的摺疊片段。 在本申請案中，術語「預防」涉及在誘導疾病或病狀之 前投與保護性組合物。「治療」涉及在疾病或病狀症狀顯 現之後投與保護性組合物。「抑制」係指在誘導事件之後 但在臨床出現疾病或病狀之前投與組合物。 如本文中所用，術語「劑量」係指一次性（單位劑量）， 或歷經規定時間間隔分兩次或兩次以上投藥來投與個體之 =位體之量。舉例而言’劑量可指歷經—天（24小時日劑 量）、兩天、一週、兩週、三週或一個月或多個月之過程 (Η藉由單-人技藥’或藉由兩次或兩次以上投藥）投與個 體之配位體（例如包含結合目標抗原之免疫球蛋白單一可 變域之配位體）之量。劑量之間的時間間隔可為任何所需 © Β夺間量。術語「醫藥學上有效」當指劑量時意謂足以提供 所需作用之配位體、域或醫藥活性劑的量。視個體之年齡 及一般狀況、特定藥物或醫藥活性劑及其類似因素而定， I有效」量將在個體之間不同。因此，並不總能明綠說明 l =於所有患者之確切「有效」量。然而，適當「有效」 〜在任何個別情況下均可由—般技術者使用常規實驗來 確定。 驗項技術者熟悉藥物動力學分析及測定配位體⑼ 如早一可變域 '融合蛋白或多特異性配位體）半衰期之方 146451.doc 201042039 法。詳情可見於尺⑼似成J等人：Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists 及 Peiers 等 人，Pharmacokinetc analysis: A Practical Approach (1996)。 亦參考「Pharmacokinetics」’ M Gibaldi 及 D Perron，Marcel Dekker出版，第2特別修訂版（1982)，其描述諸如ta及tp半 衰期及曲線下面積（AUC)之藥物動力學參數。視情況，在 本文中引用之所有藥物動力學參數及值均讀作人類之值。 視情況，在本文中引用之所有藥物動力學參數及值均讀作 小鼠或大鼠或獼猴之值。 半衰期及AUC可自配位體之血清濃度相對於 時間之曲線測定。可使用例如5.1版WinNonlin分析套件（可 獲自 Pharsight Corp.，Mountain View, CA94040，USA)，例 如以模型化曲線。當使用兩隔室模型化時，在第一階段（α 階段），配位體大部分分布於患者體内，而一些消除。第 二階段（β階段）為配位體已分布且血清濃度隨配位體自患者 清除而降低之階段。ta半衰期為第一階段之半衰期而ίβ半 衰期為第二階段之半衰期。因此，在一個實施例中，在本 發明之情形中，可變域、融合蛋白或配位體具有在（或 約）15分鐘或15分鐘以上範圍内之ta半衰期。在一個實施例 中，範圍之下限為（或為約）30分鐘、45分鐘、1小時、2小 時、3小時、4小時、5小時、6小時、7小時、10小時、11 小時或12小時。或者或另外，本發明之可變域、融合蛋白 或配位體將具有在至多且包括12小時（或約12小時）範圍内 之ta半衰期。在一個實施例中，範圍之上限為（或為 146451.doc -12- 201042039
2 2天。舉例而言，本發明之可變域、 19天、20天、21天或 融合蛋白或配位體將 具有在12至60小時（或約12至60小時）範圍内之tp半衰期。 在另一實施例中，其將在12至48小時（或約12至48小時）之 範圍内。在又一實施例中，其將在丨2至26小時（或約丨2至 26小時）之範圍内。 作為使用兩隔室模型化之替代，熟習此項技術者將熟悉 Q 使用非隔室模型化，其可用於測定終末半衰期（就此而 言，如本文中所用之術語「終末半衰期」意謂使用非隔室 模型化測定之終末半衰期）。可使用例如5.1版WinNonlin分 析套件（可獲自 Pharsight Corp·，Mountain View，CA94040, USA) ’例如以此方式模型化曲線。在此情況下，在一個 實施例中，單一可變域、融合蛋白或配位體具有至少（或 至少約）8小時、10小時、12小時、15小時、28小時、20小 時、1天、2天、3天、7天、14天、15天、16天、17天、18 天、19天、20天、21天、22天、23天、24天或25天之終末 146451.doc -13 - 201042039 半衰期。在一個實施例中，此範圍之上限為（或為約）24小 時、48小時、60小時或72小時或12〇小時。舉例而言，終 末半衰期例如在人類中為（或為約）8小時至6〇小時，或8小 時至48小時或12小時至120小時。 除上述準則以外或替代上述準則，本發明之可變域、融 合蛋白或配位體還具有在（或約）丨mg min/ml或1 mg min/mi 以上範圍内之AUC值（曲線下面積）。在一個實施例中，範 圍之下限為(或為約)5、10、15、2〇、3〇、1〇〇、或3〇(
mg.min/ml。或者或另外，本發明之可變域、融合蛋白或 配位體具有在（或約）至多6〇〇叫—範圍内之就。在 一個實施例中，範圍之上限為（或為約⑽、彻、3〇〇、 測、15〇、1〇〇、75或50mg.min/ml。可變域融合蛋白或 配位體宜具有在（或大約在）選自由以下組成之群之範圍内 的取：15 至 150 ―、15 至⑽ mg.min/nU、15至 75 mg.min/ml& 15至 5〇 mg min/mi。 衣面電聚共振」：可使用競泰 令檢&來測定特定抗原
杬原決疋基（諸如人類血清白蛋白 決定基（諸如獼猴血清白蛋白）競爭社人I 一抗原或抗 :位體(諸如特定dAb)。類似地，可使用競爭 疋來，収4如dAb之第-配位體是否與諸 位體競爭結合目標抗原或抗原決定基。如本文^用一 ::爭」係指能夠以任何程度干擾兩個或兩個以上分 之間的特異性結合相互作用的物質 較佳為蛋白質。片任「灶、☆ 刀子、化合物 賈片》。不矶甲性抑制」意謂諸如分子、 146451.doc -14· 201042039 合物’較佳為蛋白質之物質不以任何可量測或顯著之程度 干擾南個或兩個以上分子之間的特異性結合相互作用。2 個或兩個以上分子之間的特異性結合相互作用較佳包括單 -可變域與其同源搭配物或目標之間的特異性結合相互作 用。干擾或競爭分子可為另一單一可變域或其可為在結構 上及/或功能上類似於同源搭配物或目標之分子。 術語「結合部分」係指獨立於不同抗原決定基或抗原結 合域特異性結合抗原或抗原決定基之域。結合部分可為域 抗體（dAb)或可為作為非免疫球蛋白蛋白質骨架之衍生物 的域，該蛋白質骨架例如為選自由以下組成之群的骨架： CTLA_4、脂質運載蛋白、SPA、黏接素（adnectin)、親和 體（affibody)、尚親和性多聚體（avimer)、Gr〇E丨運鐵蛋白 (tmnsferdn)、&〇^及纖維結合蛋白（仙^⑽⑽叫其結合 除天然配位體以外之配位體（在本發明之情況下，該部分 結合血清白蛋白）。參看w〇 2〇〇8/〇96158，其揭示蛋白= 月架之實例及自譜系選擇抗原或抗原決定基特異性結合域 之方法（參看實例17至25)。WO 2008/096158之此等特定揭 示内谷係以引用的方式明確併入本文中，仿佛明確地書寫 於本文中一般且供本發明使用，且預期可將此揭示案之任 何部分均併入本文中之一或多個技術方案中。 在一個態樣中’本發明提供D〇M7h-11之抗血清白蛋白 (SA)免疫球蛋白單一可變域變體，其中變體與1)〇肘7^11 相比在FW2/CDR2接合點（位置49至51，根據Kabat編號）中 包含至少一個突變’且其中變體與D〇M7h-ll之胺基酸序 146451.doc 201042039 列相比具有2至8個變化。位置49(根據Kabat)視情況為 Leu。或者或另外，位置50(根據Kabat)視情況為Ala或 Trp。或者或另外，位置51(根據Kabat)視情況為Phe或 Asn。在一個實施例中，變體與DOM7h-ll相比在各位置 49、50及51(根據Kabat編號）均包含突變。在一個實施例 中’變體包含LFG基元，其中L位於位置49(根據Kabat編 號），其中L、F及G分別為Leu、Phe及Gly。 在一個實施例中，變體包含與選自DOM7h-11-3、 DOM7h-ll-15、DOM7h-ll-12 及 DOM7h-ll-19 之單一可變 域之胺基酸序列一致或與所選胺基酸序列相比具有至多4 個變化的胺基酸序列，限制條件為變體之胺基酸序列在如 上定義之FW2/CDR2接合點中具有至少一個突變。在一個 實施例中，變體包含與DOM7h-ll-15sl2P之胺基酸序列一 致或與DOM7h-l 1-15S12P之胺基酸序列相比具有至多4個變 化的胺基酸序列，限制條件為變體之胺基酸序列在 FW2/CDR2接合點（位置49至5 1，根據Kabat編號）中具有至 少一個突變。在一個實施例中’變體包含與選自D〇M7h-11-3之單一可變域之胺基酸序列一致或與所選胺基酸序列 相比具有至多4個變化的胺基酸序列，限制條件為變體之 胺基酸序列在位置49具有L、在位置50具有貿且在位置51 具有N。在一個實施例中，變體包含與選自D〇M7h-11 · 12 之單可變域之胺基酸序列一致或與所選胺基酸序列相比 具有至多4個變化的胺基酸序列，限制條件為變體之胺基 酸序列在位置32具有Μ且在位置49具有L。在一個實施例 146451 .doc •16· 201042039 中，變體包含與選自DOM7h-ll-15或DOM7h-ll-15S12P之單 一可變域之胺基酸序列一致或與所選胺基酸序列相比具有 至多4個變化的胺基酸序列，限制條件為變體之胺基酸序 列在位置32具有Μ、在位置49具有L、在位置50具有A且在 位置51具有F。在一個實施例中，變體包含與選自DOM7h-11-18之單一可變域之胺基酸序列一致或與所選胺基酸序 列相比具有至多4個變化的胺基酸序列，限制條件為變體 之胺基酸序列在位置32具有Μ且在位置87具有Η。在一個 實施例中，變體包含與選自DOM7h-ll-19之單一可變域之 胺基酸序列一致或與所選胺基酸序列相比具有至多4個變 化的胺基酸序列，限制條件為變體之胺基酸序列在位置32 具有Μ、在位置49具有L且在位置91具有T。此段落中之所 有編號均係根據Kabat。 本發明之一態樣提供DOM7h-11之抗血清白蛋白（SA)免 疫球蛋白單一可變域變體，其中變體與DOM7h-11相比在 位置32(根據Kabat編號）包含Met，且其中變體與DOM7h-ll 之胺基酸序列相比具有〇至4個其他變化。視情況，變體與 DOM7h-l 1相比在FW2/CDR2接合點（位置49至5 1，根據 Kabat編號）中包含至少一個突變。 在本發明之任何態樣的一個實施例中，變體與DOM7h-11相比包含至少一個選自以下之突變 位置49=L， 位置50=A或W， 位置51=F或N， 146451.doc -17- 201042039 位置87=H，及 位置91=T。 在一個實施例中，變體包含與選自DOM7h-ll-i2、 DOM7h-ll-15 、DOM7h-ll-15sl2P 、DOM7h-ll-l8 及 DOM7h-ll-19之單一可變域之胺基酸序列一致或與所選胺 基酸序列相比具有至多4個變化的胺基酸序列，限制條件 為變體之胺基酸序列在位置32具有Met。 在一個實施例中，變體包含一或多種以下動力學特徵： (a)變體包含如藉由表面電漿共振所測定以（或約）〇.丨nM 至（或至約）10000 nM，視情況（或約y nM至（或至 約）6000 nM之解離常數（KD)特異性結合人類sa之結 合位點； (b)變體包含如藉由表面電漿共振所測定以（或約） UXH)·4 sec·1至（或至約^，視情況（或 約）3xUT4 sed(或至約）〇1 ^之解離速率⑽_ rate)常數（Kd)特異性結合人類8八之結合位點； ⑷變體包含如藉由表面電幾共振所測定以(或約)2χΐ〇6 MW1至（或至約）lxl〇4 M-Wl，視情況（或 約）lxl〇6M.wl至（或至約士合速 率（on*)常數⑹特異性結合人類SA之結合位點； (d)變體包含如藉由表面電漿丘
釆，、振所测定以（或約）0.1 nM 至（或至約）1〇〇〇〇ηΜ，視情況（或約罐至（或至 ^侧歲解離f數（KDm異性結合獼㈣之結 合位點； 146451.doc •18- 201042039 ⑷如任何前述技術方案之變體，其中該變體包含如藉由 表面電漿共振所測定以（或約）丨5xl〇·4 “^至（或至 )1 sec ，視情況（或約）3 X1 〇-4 sec·1至（或至約）〇 1 咖-1之解離速率常數（Kd)特異性結合摘猴从之結合位 點；
⑴如任何前述技術方案之變體，其中該變體包含如藉由 表面電漿共振所測定以（或約）2xl〇6 M-kc-i至（或至 、力）1χ1〇 M Sec·丨，視情況（或約）1χ1〇6 丨至（或 至約）5xl〇 μ W-i之結合速率常數（Ka)特異性結合稠 猴S A之結合位點； (g)變It包含如藉由表面電讓共振所測定以（或約^副至 (或至約）10000 nM，視情況（或約）2〇打^1至（或至 約）_〇祕之解離常數（KD)特異性結合大鼠从之結 合位點； ⑻變體包含如藉由表面電浆共振所測定以（或約）2…·3 咖-1至（或至約）0.15 sec-丨，視情況（或約）9χΐ〇.3 ^ 至（或至約）〇.U sec-i之解離速率常數特異性結合 大鼠SA之結合位點； ⑴變體包含如II由表φ電製共振所測冑以（或約）2χΐ〇6 M sec至（或至約）1χΐ04 M-W1，視情況（或 約）1χ1〇 M^ec1至（或至約）3x1〇4 M]sec-丨之結合速 率常數（Ka)特異性結合大鼠SA之結合位點； G)變體包3如藉由表面電漿共振所測定以（或約nM至 (或至約）10000 nM之解離常數（KD)特異性結合小鼠§八 146451.doc 201042039 之結合位點； (k) 變體包含如藉由表面電漿共振所測定以（或約）2 χ丨〇-3 sec至（或至約）〇15 sec-i之解離速率常數（Kd)特異性 結合小鼠SA之結合位點；及/或 (l) 變體包含如藉由表面電漿共振所測定以（或約）2xi〇6 M sec至（或至約）ixi〇4 M_isec-i，視情況（或 約）2xl06 M'ec·1至（或至約）ι.5Χι〇4 μ-丨see·之結合速 率常數（Ka)特異性結合小鼠sa之結合位點。 視情況，變體具有 I .根據（a)及（d)之KD、根據（b)及（e)2Kd，及根據及（f) 之Ka ;或 II ·根據（a)及（g)之KD、根據（b)及（h)之Kd，及根據（c)及⑴ 之Ka ;或 III :根據（a)及⑴之KD、根據（b)及（k)2Kd，及根據（〇及 ⑴之Ka ;或 IV :根據I及II之動力學；或 V :根據I及III之動力學；或 VI :根據I、II及III之動力學。 本發明亦提供包含本發明之任何前述態樣或實施例之變 體的配位體。舉例而言，配位體可為雙特異性配位體（參 看，〇 04003019雙特異性配位體之實例）。在一個態樣中: 本發明提供多特異性配位體’其包含本發明之任何前述態 樣或實施例之抗SA變體及特異性結合除SA以外之目標抗 原的結合部分。結合部分可為特異性結合目標之任何結合 146451.doc -20- 201042039 部分’例如該部分為抗體、抗體片段、scFv、Fab、dAb或 包含非免疫球蛋白蛋白質骨架之結合部分。此等部分詳細 揭不於WO 2008/096158中（參看實例！ 7至25，其揭示内容 係以引用的方式併入本文中）。非免疫球蛋白骨架之實例 為CTLA·4、脂質運載蛋白、葡萄球菌蛋白A(SpA)、親和 體™、高親和性多聚體TM、黏接素、Gr〇EL及纖維結合蛋 白。 在一個實施例中，在抗目標結合部分與抗SA單一變體之 間提供連接子，連接子包含胺基酸序列AST，視情況為 ASTSGPS。替代性連接子描述於w〇 2〇〇7〇85814(以引用 的方式併入本文中）及w〇 2〇〇8/〇96158(參看第135頁第Η 列至第140頁第14列之段落，其揭示内容及連接子之所有 序列均以引用的方式明確併入本文中，仿佛明痛地書寫於 本文中-般且供本發明使用，且預期可將此揭示案之任何 部分併入本文中之一或多個技術方案中）中。 Q 在多特異性配位體之一個實施例中，目標抗原可為天然 存在或合成之多肽、蛋白質或核酸，或該等多肽、蛋白質 或核酉夂之部分。就此而言，本發明之配位體可結合目標抗 原且充當拮抗劑或促效劑（例如Ep〇受體促效劑）。熟習此 項技術者應瞭解選擇面較大且可變。其可為例如人類蛋白 質或動物蛋白質、細胞激素、細胞激素受體，其中細胞激 素受體包括細胞激素、酶、酶輔助因子或DNA結合蛋白之 支體適&細胞激素及生長因子包括，但較佳不限於： Ap〇E、Apo_SAA、BDNF、心營養素叩—州叫、 146451.doc •21 · 201042039 EGF、EGF受體、ENA-78、嗜酸性粒細胞趨化因子 (Eotaxin)、嗜酸性粒細胞趨化因子-2、愛德仕-2(Exodus-2)、EpoR、酸性FGF、鹼性FGF、纖維母細胞生長因子-10、FLT3 配位體、弗拉塔凱（Fractalkine)(CX3C)、 GDNF、G-CSF、GM-CSF、GF-βΙ、騰島素、1尸>^-丫、10?-I、IGF-II、IL-la、IL-ip、IL-2、IL-3、IL-4、IL-5、IL-6、IL-7、IL-8(72個胺基酸）、IL-8(77個胺基酸）、IL-9、 IL-10 、 IL-11 、 IL-12 、 IL-13 、 IL-15 、 IL-16 、 IL-17 、 IL-18(IGIF)、抑制素tx(Inhibin a)、抑制素β、IP-10、角質細 胞生長因子-2(KGF-2)、KGF、痩素（Leptin)、LIF、淋巴細 胞趨化因子（Lymphotactin)、苗勒（Mullerian)抑制物質、單 核細胞群落抑制因子、單核細胞引誘蛋白（monocyte attractant protein)、M-CSF、MDC(67個胺基酸）、MDC(69 個胺基酸）、MCP-l(MCAF) ' MCP-2、MCP-3、MCP-4、 MDC(67個胺基酸）、MDC(69個胺基酸）、MIG、ΜΙΡ-1α、 ΜΙΡ-1β、ΜΙΡ-3α、ΜΙΡ-3β、MIP-4、骨髓祖細胞抑制因 子-1 (MPIF-1)、NAP-2、神經營養因子（Neurturin)、神經生 長因子、β-NGF、NT-3、NT-4、制瘤素 M(Oncostatin Μ)、 PDGF-AA、PDGF-AB、PDGF-BB、PF-4、RANTES、 SDFla、SDFlp、SCF、SCGF、幹細胞因子（SCF)、 TARC、TGF-a、TGF-β、TGFJ2、TGF-p3、腫瘤壞死因子 (TNF)、TNF-a、TNF-β、TNF 受體 I、TNF 受體11、丁1^-1、TPO、VEGF、VEGF 受體 1、VEGF 受體 2、VEGF 受體 3、GCP-2、GRO/MGSA、GRO-β、GRO-γ、HCC1、1- 146451.doc •22- 201042039 3 09、HER 1、HER 2、HER 3及HER 4、CD4、人類趨化因 子受體CXCR4或CCR5、來自C型肝炎病毒之第3型非結構 性蛋白質（NS3)、TNF-α、IgE、IFN-γ、MMP-12、CEA、 幽門螺旋桿菌（H. pylori)、TB、流感病毒、E型肝炎、 MMP-12、在某些細胞上過表現之内化受體（諸如表皮生長 因子受體（EGFR))、腫瘤細胞上之ErBb2受體、内化細胞受 體、LDL受體、FGF2受體、ErbB2受體、運鐵蛋白受體、 PDGF受體、VEGF受體、PsmAr、細胞外基質蛋白、彈性 ® 蛋白、纖維結合蛋白、層黏連蛋白（laminin)、al-抗胰蛋 白酶、組織因子蛋白酶抑制劑、PDK1、GSK1、Bad、卡 斯蛋白酶-9(caspase-9)、叉頭（Forkhead)、幽門螺旋桿菌 (Helicobacter pylori)之抗原、結核分枝桿菌（Mycobacterium tuberculosis)之抗原及流感病毒之抗原。應瞭解此清單決 不詳盡無遺。 在一個實施例中，多特異性配位體包含本發明之抗SA dAb變體及抗TNFR1結合部分，例如抗TNFR1 dAb。視情 況，配位體僅具有一個抗TNFR1結合部分（例如dAb)以降 低受體交聯之機會。在一個實施例中，抗S A dAb變體為 DOM7h-ll-3 或 DOM7h-ll-15 或 DOM7h-ll-15sl2p。 在一個實施例中，抗TNFR1結合部分為WO 2008149148 中揭示之DOMlh-13 1-206(如該PCT申請案中所揭示之其胺 基酸序列及其核苷酸序列係以引用的方式明確併入本文 中，仿佛明確地書寫於本文中一般且供本發明使用，且預 期可將此揭示案之任何部分均併入本文中之一或多個技術 146451.doc -23- 201042039 方案中）。在一個實施例中，多特異性配位體包含以下或 由以下組成：DOMlh-131-206之胺基酸序列及DOM7h-ll-3 或 DOM7h-ll-15 或 DOM7h-ll-15sl2Pi 胺基酸序列。 在一個實施例中，抗TNFR1結合部分或dAb為任何此部 分或同在申請中之申請案USSN 61/153,746(其揭示内容係 以引用的方式併入本文中）中揭示之dAb。在一個實施例 中，抗TNFR1結合部分包含與〇0河111_574-156、001\/1111- 574-72、DOMlh_574-109、DOMlh-574-138、DOMlh-574- 162或DOMlh-574-180之胺基酸序列或表3中揭示之任何抗 TNFR1 dAb之胺基酸序列至少95%一致的胺基酸序列。在 一個實施例中，多特異性配位體包含以下或由以下組成： 〇0河111-574-156之胺基酸序列及〇01^711-11-3或00河711-11-15或DOM7h-ll-15sl2P之胺基酸序列。 在一個實施例中，本發明之配位體為包含本發明之變體 直接或間接融合於一或多種多肽之融合蛋白。舉例而言， 融合蛋白可為如WO 2005/11 8642(其揭示内容係以引用的 方式併入本文中）中揭示之「藥物融合物」，其包含本發明 之變體及如該PCT申請案中所定義之多肽藥物。 如本文中所肖，「帛物」係指任何可投與個體以經由結 合於個體中之生物目標分子及/或改變個體中生物目標分 子之功能來產生有益S療或診斷作用之化合物（例如小有 機分子、核酸、多肽）。目標分子可 不刀于了為由個體基因組編碼 之内源目標分子(例如由個體基因組編碼之酶、受體、生 長因子、細胞激素）或由病原體基因組編石馬之外源目標分 14645】.doc -24- 201042039 子（例如由病毒、細菌、真菌、線蟲或其他病原體之基因 組編碼之酶）。適用於包含本發明抗sa Mb變體之融合蛋 白及接合物的華物姐 樂物揭不於WO 2005/118642及W0 鳩⑽Η)6中（其全部揭示内容係以引用的方式明確併入 2文中，且包括特定藥物之整個清單，仿佛此清單明綠地 書寫於本文中一般，且箱f日. y ^ 預期此併入提供特定藥物之揭示以 1更：括於本文之技術方案中)。舉例而言，藥物可為升糖 = 1(GUM)或變體、干擾素❿或變體或腸 類似物-4或變體。 在一個實施财，本發明提供如w〇2〇〇5/u8642及觸 2006/059106中所定羞；5掂-— 義及揭不之藥物接合物，JL中接人物 包含本發明之變體。在—個竇如由一 /、甲接《物 個實例中，樂物係與變體丘價連 接（例如變體及藥物表現為單一 、 多肽之口P分）。或者，在一 實例中，藥物與變體非Α僭 、 、·、α或締合。藥物可與變體直 接或間接（例如經由適合遠技 峰物去m “ 或互補結合搭配物(例如 〇 ^ ^ 之非共叔結合）共價或非共價鍵 結。當採用互補結合搭配物 賈鍵 首接#八、種釔合搭配物可與藥物 直接或^由適合連接部分共價鍵結，而互補結 與變體直接或經由適合連& '° 可 連接。卩分共價鍵結。當藥 或肽時，藥物組合物可為融合 *''肽 . σ蛋白，其中多肽或肽、藥物 …部分為連續多肽鏈之不連續部分(part/ m:iety)。如本文所述’多肽結合部分及多狀藥物部分可: =彼此直接鍵結’或經由適合胺基—連： 146451.doc -25- 201042039 含有—個本發明單一可變域（單體）變體或一個以上單一 可變域（如本文所定義之多聚體、融合蛋白、接合物及雙 特異性配位體）且特異性結合血清白蛋白之配位體可進一 步包3或多個選自，但較佳不限於以下之實體：標記 (label)、標藏、另—單—可變域、⑽、抗體、抗體片 段、標記（marker)及藥物。—或多個此等實體可位於包含 單一可變域（免疫球蛋白或非免疫球蛋白單一可變域）之配 位體的COOH端或N端，或N端與c〇〇H端。一或多個此等 實體可位於含有一個單一可變域（單體）或一個以上單一可 變域（如本文所定義之多聚體、融合蛋白、接合物及雙特 異性配位體）之配位體中特異性結合血清白蛋白之單一可 變域的COOH端，或N端，或n端與COOH端。可位於此等 端中一或兩者之標籤的非限制性實例包括HA、his或myc 標籤。實體（包括一或多種標籤、標記及藥物）可直接或經 由如上所述之連接子結合於含有結合血清白蛋白之一個單 了麦域（單體）或一個以上單一可變域（如本文所定義之多 聚體、融合蛋白、接合物及雙特異性配位體）的配位體。 本發明之一態樣提供一種融合產物，例如融合蛋白或與 肽之融合物或與NCE(新穎化學實體）藥物之接合物，其包 含多肽藥物融合或接合（對於NCE)於任何如上所述之變 體’視情況其中變體為D〇M7h-ll-15或DOM7h-ll-15S12P(或具有與 DOM7h-ll-15 或 DOM7h-ll-15sl2P2 胺基酸 序列至少95%、96%、97%、98%或99% —致之胺基酸的變 體）或 DOM7h-ll-12(或具有與 DOM7h-ll-15 或 DOM7h-ll- 146451.doc -26- 201042039
S 12 P 15 之胺基酸序列至少95%、96%、97%、98%或99°/〇 — 致之胺基酸的變體）。D〇M7h-ll-15、DOM7h-ll-15sl2P& DOM7h-ll-12當融合或接合於搭配物時僅使親和力適度降 低’使得其適用於融合產物。 本發明提供一種組合物，其包含本發明之任何態樣的變 體、融合蛋白、接合物或配位體，及醫藥學上可接受之稀 釋劑、載劑、賦形劑或媒劑。 在本文中亦涵蓋編碼任何本文所述
❹ 接合物或配位體的經分離之核酸，該等配位體例如含有特 異性結合血清白蛋白，或特異性結合人類血清白蛋白與至 少一種非人類企清白蛋白的一個本發明單一可變域（單體） 變體或一個以上單一可變域變體之配位體（例如本文所定 義之多聚體、融合蛋白、接合物及雙特異性配位體），或 其功能活性片段。在本文中亦涵蓋載體及/或表現載體、 包含該載體之宿主細胞，例如經載體轉型之植物或動物細 胞及/或細胞株，表現及/或製備該等載體所編碼之一或多 種變體、融合蛋白、或含有特異性結合血清白蛋白之一個 單-可變域（單體）變體或一個以上單—可變域變體之配位 體(例如本文所定義之多聚體、融合蛋白、接合物及雙特 異性配位體）或其片段的方法，包括在—些情況下培養宿 主細胞以使該-或多種變體、融合蛋白或配位體或其片段 表現’及視情況自宿主細胞培養基回收含有特異性杜人: 清白蛋白之-個單一可變域(單體)或一個以上單一可變域 之配位體（例如本文所定義之多聚體、融合蛋白、接合物 146451.doc -27· 201042039 及雙特異性配位體）。亦涵蓋使本文所述之配位體與也清 白蛋白(包括血清白蛋白及/或非人類血清白蛋白)及/或一 或多種血清白蛋白以外之目標接觸之方法，其中該目標包 括生物活性分子，且包括動物蛋白質、上列細胞激素，及 包括活體外接觸以及活體内及/或離體投與個別宿主動物 或細胞任何本文所述之變體、融合蛋白或配位體的方法。 較佳地，投與本文所述包含針對▲清自蛋自及/或非人類 血清白蛋白之單-可變域（免疫球蛋白或非免疫球蛋白）及 -或多個針對—或多種血清白蛋白以外目標之域的配位體 將增加抗目標配位體之半衰期，包括邛及/或終半衰期。 本文涵蓋編碼變體、融合蛋白或含單一域之配位體或其片 段（包括其功能片段）的核酸分子。本文涵蓋編碼核酸分子 之載體，包括（但較佳不限於）表現載體，及含有一或多種 此等表現載體之細胞株或生物體的宿主細胞。亦涵蓋製備 任何變體、融合蛋白或配位體（包括，但較佳不限於，任 何上述核酸、載體及宿主細胞）之方法。 本心明之態樣&供包含編碼本發明變體或本發明多特 異性配位體或本發明融合蛋白之核苷酸序列的核酸。 本發明之一態樣提供一種核酸，其包含選自1)〇]^711_11_ 3、DOM7h-ll]5、DOM7h-ll-15⑴p、D〇M7h U l2、 DOM7h-ll-18 及 DOM7h-ll-19 之 DOM7h-ll 變體的核苷酸 序列或與該所選序列至少70%、75%、80%、85%、9〇%、 95/。、96%、97%、98%或99°/。一致之核苦酸序列。 本發明之一態樣提供包含本發明核酸之載體。本發明之 146451.doc 28· 201042039 一態樣提供包含載體的經分離之宿主細胞。 關於文庫載體系統、組合單一可變域、表徵雙特異性配 位體、雙特異性配位體之結構、用於構築雙特異性配位體 之骨架、抗血清白蛋白dAb及多特異性配位體及半衰期增 強之配位體的用途、及包含抗血清白蛋白dAb之組合物及 調配物的詳情，請參考WO 2008/096158。此等揭示案係以 引用的方式併入本文中以提供用於本發明之指導，包括關 於本發明之變體、配位體、融合蛋白、接合物、核酸、載 〇 體、宿主及組合物的指導。 不符合本發明之DOM7h-14變體序列揭示於同在申請中 之與本申請案同天申請的標題為IMPROVED ANTI-SERUM ALBUMIN BINDING VARIANTS之美國臨時專利申請案 中。DOM7h-14變體之此等序列（同在申請中之申請案中的 SEQ ID NO: 1-10)係以引用的方式併入本文中，仿佛明確 地書寫於本文中一般。 序列 ❹ 表1 : DOM7h-ll變體dAb之胺基酸序列 DOM7h-ll-12 (SEQ ID NO: 1)
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILFGSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR DOM7h-ll-15 (SEQ ID NO: 2)
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR DOM7h-ll-18 (SEQ ID NO: 3)
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLIWFGSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYHCAQAGTHPTTFGQGTKVEIKR DOM7h-ll-19 (SEQ ID NO; 4)
DIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILFGSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQTGTHPTTFGQGTKVEIKR •29- 146451.doc 201042039 DOM7h-ll-3 (SEQ ID NO: 5)
DIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLILWNSRLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR 表2 : DOM7h-ll變體dAb之核苷酸序列 DOM7h-ll-12 (SEQ ID NO: 6)
GACATCCAGA TGACCCAGTC TCCATCCTCC CTGTCTGCAT CTGTAGGAGA CCGTGT CACC ATCACTTGCC GGGCAAGTCG TCCGATTGGG ACGATGTTAA GTTGGTACCA GC AGAAACCA GGGAAAGCCC CTAAGCTCCT GATCTTGTTT GGTTCCCGGT TGCAAAGT GG GGTCCCATCA CGTTTCAGTG GCAGTGGATC TGGGACAGAT TTCACTCTCA CCAT CAGCAG TCTGCAACCT GAAGATTTTG CTACGTACTA CTGTGCGCAG GCTGGGACGC ATCCTACGAC GTTCGGCCAA GGGACCAAGG TGGAAATCAA ACGG DOM7h-ll-15 (SEQ ID NO： 7)
GACATCCAGA TGACCCAGTC TCCATCCTCC CTGTCTGCAT CTGTAGGAGA CCGTGT CACC ATCACTTGCC GGGCAAGTCG TCCGATTGGG ACGATGTTAA GTTGGTACCA GC AGAAACCA GGGAAAGCCC CTAAGCTCCT GATCCTTGCT TTTTCCCGTT TGCAAAGT GG GGTCCCATCA CGTTTCAGTG GCAGTGGATC TGGGACAGAT TTCACTCTCA CCAT CAGCAG TCTGCAACCT GAAGATTTTG CTACGTACTA CTGCGCGCAG GCTGGGACGC ATCCTACGAC GTTCGGCCAA GGGACCAAGG TGGAAATCAA ACGG D〇M7h-ll-18 (SEQ ID NO: 8)
GACATCCAGA TGACCCAGTC TCCATCCTCC CTGTCTGCAT CTGTAGGAGA CCGTGT CACC ATCACTTGCC GGGCAAGTCG TCCGATTGGG ACGATGTTAA GTTGGTACCA GC AGAAACCA GGGAAAGCCC CAAAGCTCCT GATCTGGTTT GGTTCCCGGT TGCAAAGT GG GGTCCCATCA CGTTTCAGTG GCAGTGGATC TGGGACAGAT TTCACTCTCA CCAT CAGCAG TCTGCAACCT GAAGATTTTG CTACGTACCA CTGTGCGCAG GCGGGGACGC ATCCTACGAC GTTCGGCCAA GGGACCAAGG TGGAAATCAA ACGG DOM7h-ll-19 (SEQ ID NO: 9)
GACATCCAGA TGACCCAGTC TCCATCCTCC CTGTCTGCAT CTGTAGGAGA CCGTGT CACC ATCACTTGCC GGGCAAGTCG TCCGATTGGG ACGATGTTAA GTTGGTACCA GC AGAAACCA GGGAAAGCCC CTAAGCTCCT GATCTTGTTT GGTTCCCGGT TGCAAAGT GG GGTCCCATCA CGTTTCAGTG GCAGTGGATC TGGGACGGAT TTCACTCTCA CCAT CAGCAG TCTGCAACCT GAAGATTTTG CTACGTACTA CTGTGCGCAG ACTGGGACGC ATCCCACGAC GTTCGGCCAA GGGACCAAGG TGGAAATCAA ACGG DOM7h-ll-3 (SEQ ID NO: 10)
GACATCCAGA TGACCCAGTC TCCATCCTCC CTGTCTGCAT CTGTAGGAGA CCGTGT CACC ATCACTTGCC GGGCAAGTCG TCCGATTGGG ACGACGTTAA GTTGGTACCA GC AGAAACCA GGGAAAGCCC CTAAGCTCCT GATCCTTTGG AATTCCCGTT TGCAAAGT GG GGTCCCATCA CGTTTCAGTG GCAGTGGATC TGGGACAGAT TTCACTCTCA CCAT CAGCAG TCTGCAACCT GAAGATTTTG CTACGTACTA CTGTGCGCAG GCTGGGACGC ATCCTACGAC GTTCGGCCAA GGGACCAAGG TGGAAATCAA ACGG 表3 :抗TNFR1 dAb之胺基酸序列 ·30·
146451.doc 201042039 >DOMlh-509 (SEQ ID NO: 11)
EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYRMHWVRQAPGKSLEWVSSIDTRGSST
YYADPVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAVTMFSPFFDYWGQGTLV
TVSS >D〇Mlh-510 (SEQ ID NO： 12)
EVQLLESGGGLVQPGGSLRLSCAASGFTFADYGMRWVRQAPGKGLEWVSSITRTGRVT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKWRNRHGEYLADFDYWGQG
TLVTVSS >DOMlh-543 (SEQ ID NO： 13)
EVQLLESGGGLVQPGGSLRLSCAASGFTFMRYRMHWVRQAPGKGLEWVSSIDSNGSST
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDRTERSPVFDYWGQGTLV
TVSS >DOMlh-549 (SEQ ID NO： 14) EVQLLESGGGLVQPGGSLRLSCAASGFTFVDYEMHWVRQAPGKGLEWVSSISESGTTT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRRFSASTFDYWGQGTLVT 〇 vss >D〇Mlh-57 4 (SEQ ID NO： 15)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGHWEPFDYWGQGTLVT
VSS >DOMlh-574-l (SEQ ID NO: 16)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGRWEPYDYWGQGTLVT
VSS >DOMlh-574-2 (SEQ ID NO: 17)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGRWEPFDYWGQGTLVT
VSS G >DOMlh-574-7 (SEQ ID NO: 18)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-8 (SEQ ID NO: 19)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-9 (SEQ ID NO: 20)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYMQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-10 (SEQ ID NO: 21)
EVQLLESGGGLVQPGGSLRLSCAASGFTFGKYSMGWVRQAPGKDLEWVSQISNTGGHT -31· 146451.doc 201042039
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-ll (SEQ ID NO: 22)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGRWEPFDHWGQGTLVT
VSS >DOMlh-574-12 (SEQ ID NO: 23)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGRWEPFDYWGQGTLVT
VSS >D〇Mlh-574-13 (SEQ ID NO： 24)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-14 (SEQ ID NO： 25)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-15 (SEQ ID NO： 26)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >D〇Mlh-574-16 (SEQ ID NO: 27)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-17 (SEQ ID NO: 28)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISNTGDHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-18 (SEQ ID NO: 29)
EVQLLESGGGLVQPGGSLRLSCAASGFTFGKYSMGWVRQAPGKDLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-19 (SEQ ID NO: 30)
EVQLLESGGGLVQPGGSLRLSCAASGFTFGKYSMGWVRQAPGKDLEWVSQISNTGDHT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-25 (SEQ ID NO: 31)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS •32-
146451.doc 201042039 >DOMlh-574-26 (SEQ ID NO: 32)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFEYWGQGTLVT
VSS >D〇Mlh-57 4-27 (SEQ ID NO: 33)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWKPFEYWGQGTLVT
VSS >DOMlh-574-28 (SEQ ID NO: 34)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >D〇Mlh-574-29 (SEQ ID NO: 35)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT 〇 YYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVI1 VSS >DOMlh-574-30 (SEQ ID NO: 36)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAAYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-31 (SEQ ID NO: 37)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCMYTGRWEPFNYWGQGTLVT
VSS >DOMlh-574-32 (SEQ ID NO: 38)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
>DOMlh-574-33 (SEQ ID NO: 39)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTAVYYCAIYTGRWVPFDNWGQGTLVT
VSS >DOMlh-574-35 (SEQ ID NO: 40)
EVQLLESGGGLVQPGGSLRLSCAASGFTFITYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFQYWGQGTLVT
VSS >DOMlh-574-36 (SEQ ID NO: 41)
EVQLLESGGGLVQPGGSLRLSCAASGFTFGKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >D〇Mlh-574-37 (SEQ ID NO: 42) •33· 146451.doc 201042039
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-38 (SEQ ID NO: 43)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >D〇Mlh-574-39 (SEQ ID NO: 44)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >D〇Mlh-574-40 (SEQ ID NO: 45)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFKYWGQGTLVT
VSS >DOMlh-574-53 (SEQ ID NO: 46)
EVQLLESGGGLVQPGGSLRLSCAASGFTFSKYSMGWVRQAPGKGLEWVSQISNTGERR
YYADSVKGRFTISRDNPKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFEYWGQGTLVT
VSS >DOMlh-574-54 (SEQ ID NO: 47)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVNYSMGWVRQAPGKGLEWVSQISNTGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPYEYWGQGTLVT
VTS >D〇Mlh-57 4-65 (SEQ ID NO: 48)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-66 (SEQ ID NO: 49)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWKPFEYWGQGTLVT
VSS >D〇Mlh_574-67 (SEQ ID NO: 50)
EVQLLESGGGLVQPGGSLRLSCAASGPTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-68 (SEQ ID NO: 51)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT
VSS -34-
146451.doc 201042039 >DOMlh-574-69 (SEQ ID NO: 52)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-70 (SEQ ID NO: 53)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAVYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-71 (SEQ ID NO: 54)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWKPFEYWGQGTLVT VSS >D〇Mlh—574-72 (SEQ ID NO: 55)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT VSS >D〇Mlh-574-73 (SEQ ID NO: 56)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT VSS >D〇Mlh-574 — 74 (SEQ ID NO: 57)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT VSS >DOMlh-574-75 (SEQ ID NO: 58)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-76 (SEQ ID NO： 59)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRPTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWKPFEYWGQGTLVT VSS >DOMlh-574-77 (SEQ ID NO: 60)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT VSS >DOMlh-574-78 (SEQ ID NO: 61)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT
VSS •35- 14645】.doc 201042039 >DOMlh-574-79 (SEQ ID NO: 62)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-84 (SEQ ID NO: 63)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-85 (SEQ ID NO: 64)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWKPFEYWGQGTLVT
VSS >D〇Mlh-574-86 (SEQ ID NO: 65)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSL_DTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-87 (SEQ ID NO: 66)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT
VSS >D〇Mlh-57 4-88 (SEQ ID NO: 67)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-90 (SEQ ID NO: 68)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKFSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-91 (SEQ ID NO: 69)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-92 (SEQ ID NO: 70)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-93 (SEQ ID NO: 71)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS •36· 146451.doc 201042039 >D〇Mlh-574-94 (SEQ ID NO: 72)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAAYYCAIYTGRWPDFDYWGQGTLVT
VSS >DOMlh-574-95 (SEQ ID NO: 73)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAAYYCAIYTGRWPDFEYWGQGTLVT
VSS >DOMlh-574-96 (SEQ ID NO: 74)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWPDFDYWGQGTLVT
VSS >D〇Mlh-574-97 (SEQ ID NO: 75)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWPDFEYWGQGTLVT
VSS >DOMlh-574-98 (SEQ ID NO: 76)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWPDFDYWGQGTLVT VSS >D〇Mlh—574-99 (SEQ ID NO: 77)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWPDFEYWGQGTLVT
VSS >DOMlh-574-100 (SEQ ID NO： 78)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISAWGDRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-101 (SEQ ID NO: 79)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISDGGQRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-102 (SEQ ID NO: 80)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISDSGYRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT VSS >DOMlh-574-103 (SEQ ID NO: 81)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISDGGTRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS • 37- 146451.doc 201042039 >DOMlh-574-104 (SEQ ID NO: 82)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISDKGTRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >D〇Mlh—574-105 (SEQ ID NO: 83)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISETGRRT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-106 (SEQ ID NO: 84)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQINNTGSTT
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFDYWGQGTLVT
VSS >DOMlh-574-107 (SEQ ID NO: 85)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
>DOMlh-574-108 (SEQ ID NO: 86)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGPEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-109 (SEQ ID NO: 87)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-110 (SEQ ID NO: 88)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-lll (SEQ ID NO: 89) 0
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT
VSS >D〇Mlh-57 4-112 (SEQ ID NO:90)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYTHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-113 (SEQ ID NO:91)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRR
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS • 38 - 146451.doc 201042039 >DOMlh-574-114 (SEQ ID NO: 92)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQILNTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-115 (SEQ ID NO: 93)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >D〇Mlh—574-116 (SEQ ID NO: 94)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRR
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-117 (SEQ ID NO: 95)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRR A YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
〇 VSS >D〇Mlh-574-118 (SEQ ID NO: 96)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAVYTGRWVSFEYWGQGTLVT
VSS >DOMlh-574-119 (SEQ ID NO:97)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCALYTGRWVSFEYWGQGTLVT
VSS >DOMlh-574-120 (SEQ ID NO: 98)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAVYTGRWVPFEYWGQGTLVT
VSS
>DOMlh-574-121 (SEQ ID NO: 99)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCALYTGRWVPFEYWGQGTLVT
VSS >D〇Mlh-574-122 (SEQ ID NO: 100)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTADRR
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >D〇Mlh-574-123 (SEQ ID NO: 101)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS -39- 146451.doc 201042039 >DOMlh-574-124 (SEQ ID NO: 102)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGDRR
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >D〇Mlh-574-125 (SEQ ID NO: 103) EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTADRR YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT VSS * >DOMlh-574-126 (SEQ ID NO： 104)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >D〇Mlh-574-127 (SEQ ID NO: 105)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTADRR
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCMYTGRWEPFVYWGQGTLVT
>DOMlh-574-128 (SEQ ID NO: 106)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTADRR
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-129 (SEQ ID NO: 107)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIVNTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >D〇Mlh—57 4-130 (SEQ ID NO： 108)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIANTGDRR
YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >D〇Mlh-574-131 (SEQ ID NO: 109) 〇
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-132 (SEQ ID NO: 110)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT
VSS >DOMlh-574-133 (SEQ ID NO: 111)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS •40· 146451.doc 201042039 >D〇Mlh-57 4-134 (SEQ ID NO: 112)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYSHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-135 (SEQ ID NO: 113)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYTHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-137 (SEQ ID NO: 114)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYTDAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >D〇Mlh-574-138 (SEQ ID NO: 115)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT ▲ YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
〇 VSS >DOMlh-574-139 (SEQ ID NO: 116)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-140 (SEQ ID NO: 117)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQIADTGDRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-141 (SEQ ID NO： 118)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS © >DOMlh-574-142 (SEQ ID NO: 119)
EVQLLESGGGLVQPGGSLRLSCAASGFTFTKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-143 (SEQ ID NO: 120)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDDAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-144 (SEQ ID NO: 121)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQIADTADRR
YYDDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS -41 · 146451.doc 201042039 >DOMlh-574-145 (SEQ ID NO: 122)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQIADTGDRR
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-146 (SEQ ID NO: 123)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQIADTGDRR
YYDDAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
VSS >DOMlh-574-147 (SEQ ID NO: 124)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWGPFVYWGQGTLVT
VSS >DOMlh-574-148 (SEQ ID NO: 125)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFAYWGQGTLVT
VSS >DOMlh-574-149 (SEQ ID NO: 126)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWGPFQYWGQGTLVT
VSS >D〇Mlh-574-150 (SEQ ID NO: 127)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFQYWGQGTLVT
VSS >D〇Mlh—574-151 (SEQ ID NO: 128)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-152 (SEQ ID NO: 129)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFQYWGQGTLVT
VSS >D〇Mlh-574-153 (SEQ ID NO： 130)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFQYWGQGTLVT
VSS >D〇Mlh—574-154 (SEQ ID NO: 131)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS -42- 146451.doc 201042039 >DOMlh-574-155 (SEQ ID NO: 132)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >D〇Mlh-574-156 (SEQ ID NO: 133)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT VSS >D〇Mlh-57 4 —157 (SEQ ID NO: 134)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT VSS >DOMlh-574-158 (SEQ ID NO: 135)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWRPFEYWGQGTLVT VSS >DOMlh-574-159 (SEQ ID NO: 136)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT VSS >D〇Mlh-574-160 (SEQ ID NO: 137)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT VSS >DOMlh-574-161 (SEQ ID NO： 138)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYSHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >D〇Mlh-574-162 (SEQ ID NO: 139)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYSHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT VSS >D〇Mlh-574-163 (SEQ ID NO: 140)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYTHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT VSS >DOMlh-574-164 (SEQ ID NO: 141)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYTHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS • 43- 146451.doc 201042039 >DOMlh-574-165 (SEQ ID NO： 142)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-166 (SEQ ID NO: 143)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >DOMlh-574-167 (SEQ ID NO: 144)
EVQLLESGGGLVQPGGSLRLSCAASGFTFLKYSMGWVRQAPGKGLEWVSQISDTGDRR
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT VSS >D〇Mlh-574-169 (SEQ ID NO: 145)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRT
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-170 (SEQ ID NO: 146)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-171 (SEQ ID NO: 147)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRT
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCMYTGRWVPFEYWGQGTLVT
VSS >D〇Mlh-574-172 (SEQ ID NO: 148)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRT
YYDHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >D〇Mlh-574-173 (SEQ ID NO: 149)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRR
YYAHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT VSS >D〇Mlh—574-174 (SEQ ID NO: 150)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRR
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >D〇Mlh-57 4-17 5 (SEQ ID NO: 151)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRR
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS -44·
146451.doc 201042039 >D〇Mlh-574-17 6 (SEQ ID NO: 152)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRR
YYDHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >D〇Mlh-574-177 (SEQ ID NO: 153)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRR
YYDHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >D〇Mlh-574-178 (SEQ ID NO: 154)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQIADTADRR
YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT
VSS >D〇Mlh-574-17 9 (SEQ ID NO: 155)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTADRR 森 YYDDAVKGRFTITRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWEPFVYWGQGTLVT
〇 VSS >DOMlh-574-180 (SEQ ID NO: 156)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISDTADRT
YYAHAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWVPFEYWGQGTLVT
VSS >DOMlh-574-4 (SEQ ID NO: 157)
EVQLLESGGGLVQPGGSLRLSCAASGFTFVKYSMGWVRQAPGKGLEWVSQISNTGGHT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTGRWEPFEYWGQGTLVT VSS >DOMlh_574-168 (SEQ ID NO： 158)
EVQLLESGGGLVQPGGSLRLSCAASGFTFFKYSMGWVRQAPGKGLEWVSQISDTGDRR YYDHSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAIYTGRWAPFEYWGQGTLVT VSS
表4 :抗TNFR1 dAb之核苷酸序列 >DOMlh-509 (SEQ ID NO: 417)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTAGTCAGTATAGGATGCATTGGGTCCGCCA
GGCTCCAGGGAAGAGTCTAGAGTGGGTCTCAAGTATTGATACTAGGGGTTCGTCTACA
TACTACGCAGACCCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAAGCTGTGACGATGTTTTCTCCTTTTTTTGACTACTGGGGTCAGGGAACCCTGGTC
ACCGTCTCGAGC >DOMlh-510 (SEQ ID NO: 418)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGCTGATTATGGGATGCGTTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTACGCGGACTGGTCGTGTTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC -45· 146451.doc 201042039
GAAATGGCGGAATCGGCATGGTGAGTATCTTGCTGATTTTGACTACTGGGGTCAGGGA
ACCCTGGTCACCGTCTCGAGC >DOMlh-543 (SEQ ID NO: 159)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTATGAGGTATAGGATGCATTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCGATTGATTCTAATGGTTCTAGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAAGATCGTACGGAGCGTTCGCCGGTTTTTGACTACTGGGGTCAGGGAACCCTGGTC
ACCGTCTCGAGC >DOMlh-549 (SEQ ID NO: 160)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTGATTATGAGATGCATTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCATCTATTAGTGAGAGTGGTACGACGACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAACGTCGTTTTTCTGCTTCTACGTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574 (SEQ ID NO: 161)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCATTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-l (SEQ ID NO: 162)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCGTTGGGAGCCTTATGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-2 (SEQ ID NO: 163)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-4 (SEQ ID NO: 164)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA •46·
146451.doc 201042039
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCGTTGGGAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-180 (SEQ ID NO: 165)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-7 (SEQ ID NO: 166)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >D〇Mlh-574-8 (SEQ ID NO: 167)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACA GTCTCGAGC >DOMlh-574-9 (SEQ ID NO: 168)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATATCCCGCGACAATTCCAAGAACA
CGCTGTATATGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >D〇Mlh-574-10 (SEQ ID NO: 169)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGGTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGATCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 47- 146451.doc 201042039 >DOMlh-574-ll (SEQ ID NO: 170)
GAGGTGCAGCTGTTGGAGTCAGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGGTCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCGTTGGGAGCCTTTTGACCACTGGGGTCAGGGGACCCTGGTCACC
GTCTCGAGC >DOMlh-574-12 (SEQ ID NO: 171)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-13 (SEQ ID NO： 172)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GAAATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-14 (SEQ ID NO: 173)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGAC7VATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-15 (SEQ ID NO: 174)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-16 (SEQ ID NO: 175)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACA 48-
146451.doc 201042039
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACA
GTCTCGAGC >DOMlh-574-17 (SEQ ID NO: 176)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACA
GTCTCGAGC >DOMlh-574-18 (SEQ ID NO: 177)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGGTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGATCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC 〇 GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-19 (SEQ ID NO: 178)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGGTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGATCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCATACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-25 (SEQ ID NO: 179)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-57 4-26 (SEQ ID NO: 180)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-27 (SEQ ID NO: 181)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA -49- 146451.doc 201042039
TACTACGCGGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-28 (SEQ ID NO: 182)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-29 (SEQ ID NO: 183)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh—574-3〇 (SEQ ID NO: 184)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGCATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-31 (SEQ ID NO: 185)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTAACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-32 (SEQ ID NO: 186)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-33 (SEQ ID NO: 187)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC -50-
146451.doc 201042039
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACT
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGTGCCTTTTGACAACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh—57 4-35 (SEQ ID NO: 188)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTATTACGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTCAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-36 (SEQ ID NO: 189)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC %J TCTCCTGTGCAGCCTCCGGATTCACCTTTGGTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA TACTACGCGGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >D〇Mlh-574-37 (SEQ ID NO: 190)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAAGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC
>DOMlh-574-38 (SEQ ID NO: 191)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-39 (SEQ ID NO: 192)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC •51 - 146451.doc 201042039 >DOMlh-574-40 (SEQ ID NO: 193)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTAAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh_574-53 (SEQ ID NO: 194)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTAGTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGAGCGTAGA
TACTACGCAGACTCAGTGAAGGGCCGGTTCACCATCTCCCGCGACAATCCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGAGCCTTTTGAATACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-54 (SEQ ID NO: 195)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAACTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTACA
TACTACGCGGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTATGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCACGAGC >DOMlh-574-65 (SEQ ID NO: 196)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGATAATTCCAAGAACA
CACTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-66 (SEQ ID NO: 197)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-67 (SEQ ID NO: 198)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCT^ATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC •52-
146451.doc 201042039
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-68 (SEQ ID NO: 199)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-69 (SEQ ID NO: 200)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC 〇 GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-70 (SEQ ID NO: 201)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GGTATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-71 (SEQ ID NO: 202)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA 八 TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGT^ACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC GATATATACGGGTCGTTGGAAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-72 (SEQ ID NO: 203)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-73 (SEQ ID NO: 204)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA -53- 146451.doc 201042039
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-74 (SEQ ID NO: 205)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-75 (SEQ ID NO: 206)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGC7VAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-7 6 (SEQ ID NO: 207)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCCCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAT^ATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-77 (SEQ ID NO: 208)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh—574-78 (SEQ ID NO: 209)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 54·
146451.doc 201042039 >D〇Mlh-574-79 (SEQ ID NO: 210)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh—57 4-84 (SEQ ID NO: 211)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC O >DOMlh-574-85 (SEQ ID NO: 212)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAAGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-86 (SEQ ID NO: 213)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCCCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAAGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-87 (SEQ ID NO: 214)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-88 (SEQ ID NO: 215)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC •55· 146451.doc 201042039
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-90 (SEQ ID NO： 216)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTTTTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-57 4-91 (SEQ ID NO: 217)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-92 (SEQ ID NO: 218)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-93 (SEQ ID NO: 219)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGT^ACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >D〇Mlh-574-94 (SEQ ID NO： 220)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGCATATTACTGTGC
GATATATACGGGTCGGTGGCCCGACTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-95 (SEQ ID NO: 221)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA •56-
146451.doc 201042039
TACTACGCAGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGCATATTACTGTGC
GATATATACGGGTCGGTGGCCCGACTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-96 (SEQ ID NO: 222)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGCCCGACTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-97 (SEQ ID NO: 223)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA 〇 TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC GATATATACGGGTCGGTGGCCCGACTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-98 (SEQ ID NO: 224)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGCCCGACTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-99 (SEQ ID NO: 225)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGCCCGACTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-100 (SEQ ID NO: 226)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGGCCTGGGGTGACAGGACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 57- 146451.doc 201042039 >DOMlh-574-101 (SEQ ID NO: 227)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGGACGGCGGTCAGAGGACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-102 (SEQ ID NO:228)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGGACTCCGGTTACCGCACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-103 (SEQ ID NO: 229)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCCAGAGTGGGTCTCACAGATTTCGGACGGGGGTACGCGGACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-104 (SEQ ID NO: 230)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGGACAAGGGTACGCGCACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-57 4-105 (SEQ ID NO: 231)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGATGGGTCCGCCA
GGCTCCAGGGAAAGGTCCAGAGTGGGTCTCACAGATTTCGGAGACCGGTCGCAGGACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-106 (SEQ ID NO: 232)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTAACAATACGGGTTCGACCACA
TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC •58·
146451.doc 201042039
GATATATACGGGTCGTTGGGAGCCTTTTGACTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-107 (SEQ ID NO: 233)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCCAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACT^ATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-108 (SEQ ID NO: 234)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCCAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC Q GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-109 (SEQ ID NO: 235)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-110 (SEQ ID NO: 236)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-lll (SEQ ID NO： 237)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-112 (SEQ ID NO: 238)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA •59- 146451.doc 201042039
TACTACACACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-113 (SEQ ID NO: 239)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGCAGA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh—57 4-114 (SEQ ID NO: 240)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTTGAATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-115 (SEQ ID NO: 241)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574 —116 (SEQ ID NO: 242)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTAGA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-117 (SEQ ID NO： 243)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTAGA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 60-
146451.doc 201042039 >DOMlh-574-118 (SEQ ID NO: 244)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GGTATATACTGGGCGTTGGGTGTCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-119 (SEQ ID NO: 245)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GCTATATACTGGGCGTTGGGTGTCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC o >D〇Mlh-574 —120 (SEQ ID NO： 246)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTTACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GGTATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-121 (SEQ ID NO: 247)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GCTATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-122 (SEQ ID NO: 248)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACTGCTGATCGTAGA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-123 (SEQ ID NO: 249)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC •61 - 146451.doc 201042039
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-124 (SEQ ID NO： 250)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCGGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACGGGCGATCGTAGA
TACTACGCACACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-125 (SEQ ID NO: 251)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACTGCTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-126 (SEQ ID NO: 252)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCACACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574 —127 (SEQ ID NO: 253)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGAATACTGCTGATCGTAGA
TACTACGCACACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-128 (SEQ ID NO: 254)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGCTGATCGTAGA
TACTACGCACACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCT^AGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-129 (SEQ ID NO: 255)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGTGAATACGGGTGATCGTAGA -62-
146451.doc 201042039
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-130 (SEQ ID NO: 256)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGAATACGGGTGATCGTAGA
TACTACGCAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-131 (SEQ ID NO: 257)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA 〇 TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >D〇Mlh-574-132 (SEQ ID NO: 258)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-133 (SEQ ID NO: 259)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
O
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-134 (SEQ ID NO: 260)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACTCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 63- 146451.doc 201042039 >DOMlh-574-135 (SEQ ID NO: 261)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACACACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-137 (SEQ ID NO: 262)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACACAGACGCGGTGAAGGGGCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-138 (SEQ ID NO: 263)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-139 (SEQ ID NO: 264)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-140 (SEQ ID NO: 265)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACGGGTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh—574-141 (SEQ ID NO: 266)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC -64-
146451.doc 201042039
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-142 (SEQ ID NO: 267)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGCC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATCACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAACCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-143 (SEQ ID NO: 268)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCT^GTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACGGGTGATCGTAGA
TACTACGATGACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-144 (SEQ ID NO: 269)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTAGA
TACTACGATGACTCTGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-145 (SEQ ID NO: 270)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACGGGTGATCGTAGA
TACTACGATCACTCTGTGAAGGGCCGGTTCACTATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-146 (SEQ ID NO: 271)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACGGGTGATCGTAGA
TACTACGATGACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-147 (SEQ ID NO: 272)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA -65- 146451.doc 201042039
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGGGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-148 (SEQ ID NO: 273)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGTGCCTTTTGCCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-149 (SEQ ID NO: 274)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGGACCTTTTCAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-150 (SEQ ID NO: 275)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTCAGTACTGGGGTCAGGGAACTCTGGTCACC
GTCTCGAGC >DOMlh-574-151 (SEQ ID NO: 276)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-152 (SEQ ID NO: 277)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGCGCCTTTTCAGTACTGGGGTCAGGGAACTCTGGTCACC
GTCTCGAGC 66- 146451.doc 201042039 >DOMlh-574-153 (SEQ ID NO: 278)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGTGCCTTTTCAGTACTGGGGTCAGGGCACCCTGGTCACC
GTCTCGAGC >DOMlh-574-154 (SEQ ID NO: 279)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACCGGTGATCGTAGA TACTACGATCACTCTGTGAAGGGCCGGTTCACTATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC 秦 GTCTCGAGC 〇 >D〇Mlh-574-155 (SEQ ID NO: 280)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-156 (SEQ ID NO: 281)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-157 (SEQ ID NO: 282)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-158 (SEQ ID NO: 283)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC -67- 146451.doc 201042039
GATATATACGGGTCGTTGGAGGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-159 (SEQ ID NO: 284)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAG.CCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-160 (SEQ ID NO:285)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGT^AGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGT^ACCCTGGTCACC
GTCTCGAGC >DOMlh-574-161 (SEQ ID NO: 286)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACTCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOHlh-574-162 (SEQ ID NO: 287)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACTCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-163 (SEQ ID NO: 288)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACACACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-164 (SEQ ID NO: 289)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA •68·
146451.doc 201042039
TACTACACACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-165 (SEQ ID NO: 290)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-166 (SEQ ID NO: 291)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA 〇 TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC GATATATACGGGTCGTTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC GTCTCGAGC >DOMlh-574-167 (SEQ ID NO: 292)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTGAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACCGGTGATCGTAGA
TACTACGATCACTCTGTGAAGGGCCGGTTCACTATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-168 (SEQ ID NO: 293)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACCGGTGATCGTAGA
TACTACGATCACTCTGTGAAGGGCCGGTTCACTATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-169 (SEQ ID NO: 294)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTACA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGCGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 69- 146451.doc 201042039 >DOMlh-574-170 (SEQ ID NO: 295)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTACA
TACTACGCACACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCA7U\TGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-171 (SEQ ID NO: 296)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTACA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-172 (SEQ ID NO: 297)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTACA
TACTACGATCACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCTGAGGACACCGCGGTATATTACTGTGC
GATATATACTGGGCGTTGGGTGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >D〇Mlh-574-173 (SEQ ID NO: 298)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTAGA
TACTACGCACACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-174 (SEQ ID NO: 299)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTAGA
TACTACGCACACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-175 (SEQ ID NO: 300)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTAGA
TACTACGCACACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC • 70-
146451.doc 201042039
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-176 (SEQ ID NO: 301)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTAGA
TACTACGATCACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-177 (SEQ ID NO: 302)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTAGA TACTACGATCACGCGGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC 〇 GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGGACCCTGGTCACC GTCTCGAGC >D〇Mlh-574-178 (SEQ ID NO: 303)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTGTTAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTGCGGATACTGCTGATCGTAGA
TACTACGATCACTCCGTGAAGGGCCGGTTCACCATCTCCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGGTGGGCGCCTTTTGAGTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC >DOMlh-574-179 (SEQ ID NO: 304)
GAGGTGCAGCTGCTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGCGTC
TCTCCTGTGCAGCCTCCGGATTCACCTTTTTCAAGTATTCGATGGGGTGGGTCCGCCA
GGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACAGATTTCGGATACTGCTGATCGTAGA
TACTACGATGACGCGGTGAAGGGCCGGTTCACCATCACCCGCGACAATTCCAAGAACA
CGCTGTATCTGCAAATGAACAGCCTGCGTGCCGAGGACACCGCGGTATATTACTGTGC
GATATATACGGGTCGTTGGGAGCCTTTTGTCTACTGGGGTCAGGGAACCCTGGTCACC
GTCTCGAGC 表5:抗血清白蛋白dAb(DOM7h)融合物 (用於大II研究）： DOM7h_14/腸促胰島素類似物-4融合物DMS編號7138 胺基酸序列（SEQ ID NO: 305)
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRS
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGAALPRTFGQGTKVEIK
R -71 · 146451.doc 201042039 核苷酸序列（SEQ ID NO: 306)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCAGTGGATTGGGT
CTCAGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCATGTGGCGTTCCTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAG
TGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGAT
TTTGCTACGTACTACTGTGCTCAGGGTGCGGCGTTGCCTAGGACGTTCGGCC
AAGGGACCAAGGTGGAAATCAAACGG DOM7h-14-10/腸促胰島素類似物-4融合物DMS編號7139 胺基酸序列（SEQ ID NO: 307)
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWR
SSLQSGVPSRPSGSGSGTDFTLTISSLQPEDFATYYCAQGLRHPKTFGQGTKVEIK
R 核苷酸序列（SEQ ID NO: 308)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCAGTGGATTGGGT
CTCAGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCATGTGGCGTTCCTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAG
TGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGAT
TTTGCTACGTACTACTGTGCTCAGGGTTTGAGGCATCCTAAGACGTTCGGCC
AAGGGACCAAGGTGGAAATCAAACGG 〇〇]\1711-14-18/腸促胰島素類似物-4融合物〇1\18編號7140 胺基酸序列（SEQ ID NO: 3 09)
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRS
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGLMKPMTFGQGTKVEIK
R 核苷酸序列（SEQ ID NO: 310)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC 146451.doc 72· 201042039
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCAGTGGATTGGGT
CTCAGTTATCTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCATGTGGCGTTCCTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAG
TGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGAT
TTTGCTACGTACTACTGTGCTCAGGGTCTTATGAAGCCTATGACGTTCGGCC
AAGGGACCAAGGTGGAAATCAAACGG DOM7h-14-19/腸促胰島素類似物-4融合物MS編號7141 胺基酸序列（SEQ ID NO: 311)
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRVTISCRASQWIGSQLSWYQQKPGEAPKLLIMWRS
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGAALPRTFGQGTKVEIK
R 〇 核苷酸序列（SEQ ID NO: 312)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCTCTTGCCGGGCAAGTCAGTGGATTGGGTC
TCAGTTATCTTGGTACCAGCAGAAACCAGGGGAAGCCCCTAAGCTCCTGAT
CATGTGGCGTTCCTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGT
GGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATT
TTGCTACGTACTACTGTGCTCAGGGTGCGGCGTTGCCTAGGACGTTCGGCCA
AGGGACCAAGGTGGAAATCAAACGG DOM7h-ll/腸促胰島素類似物-4融合物 MS編號7142 胺基酸序列（SEQ ID NO: 313) Ο
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLSWYQQKPGKAPKLLIWFGSR
LQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR 核苷酸序列（SEQ ID NO: 314)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTCCGATTGGGA
CGACGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCTGGTTTGGTTCCCGGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAG
TGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGAT
TTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCC
AAGGGACCAAGGTGGAAATCAAACGG 146451.doc -73- 201042039 DOM7h-ll-12/腸促胰島素類似物-4融合物DMS編號7147 胺基酸序列（SEQ ID NO: 315)
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILFGSR
LQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR 核苷酸序列（SEQ ID NO: 316)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTCCGATTGGGA
CGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCTTGTTTGGTTCCCGGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAG
TGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGAT
TTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACGACGTTCGGCC
AAGGGACCAAGGTGGAAATCAAACGG DOM7h-ll-15/腸促胰島素類似物-4融合物DMS編號7143 胺基酸序列（SEQ ID NO: 317)
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSGGGGGSGGGGSGGG
GSDIQMTQSPSSLSASVGDRYTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSR
LQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKYEIKR 核苷酸序列（SEQ ID NO: 318)
CATGGTGAAGGAACATTTACCAGTGACTTGTCAAAACAGATGGAAGAGGAG
GCAGTGCGGTTATTTATTGAGTGGCTTAAGAACGGAGGACCAAGTAGCGGG
GCACCTCCGCCATCGGGTGGTGGAGGCGGTTCAGGCGGAGGTGGCAGCGGC
GGTGGCGGGTCGGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCAT
CTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTCCGATTGGGA
CGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGA
TCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGT
GGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATT
TTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCA
AGGGACCAAGGTGGAAATCAAACGG DOM7hl4-10/G4SC-NCE融合物 編碼DOM7hl4-10/G4SC之胺基酸序列（SEQ ID NO: 319)
DIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRSSL
QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGLRHPKTFGQGTKVEIKRG
GGGSC 146451.doc • 74- 201042039 可例如使用順丁烯二醯亞胺鍵聯使c端半胱胺酸連接於 新穎化學實體（醫藥化合物，NCE)。 編碼 DOM7hl4-10/G4SC 之核苷酸序列（SEQ ID NO: 320)
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACC
GTGTCACCATCACTTGCCGGGCAAGTCAGTGGATTGGGTCTCAGTTATCTTG
GTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCATGTGGCGTTC
CTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGAC
AGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCTACGTAC
TACTGTGCTCAGGGTTTGAGGCATCCTAAGACGTTCGGCCAAGGGACCAAG
GTGGAAATCAAACGGGGTGGCGGAGGGGGTTCCTGT DOM7hl4-10/TVAAPSC融合物 〇 胺基酸序列（SEQ ID NO: 321)
DIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRSSL
QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGLRHPKTFGQGTKVEIKRT
VAAPSC 可例如使用順丁烯二醢亞胺鍵聯使C端半胱胺酸連接於 新穎化學實體（醫藥化合物，NCE)。 核苷酸序列（SEQ ID NO: 322)
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACC
GTGTCACCATCACTTGCCGGGCAAGTCAGTGGATTGGGTCTCAGTTATCTTG
GTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCATGTGGCGTTC
CTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGAC
AGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCTACGTAC
TACTGTGCTCAGGGTTTGAGGCATCCTAAGACGTTCGGCCAAGGGACCAAG
GTGGAAATCAAACGGACCGTCGCTGCTCCATCTTGT (用於小鼠研究）： DOM7h-ll/DOMlm-21-23融合物 DMS編號 5515 胺基酸序列（SEQ ID NO: 323)
EVQLLESGGGLVQPGGSLRLSCAASGFTFNRYSMGWLRQAPGKGLEWVSRIDS
YGRGTYYEDPVKGRFSISRDNSKNTLYLQMNSLRAEDTAVYYCAKISQFGSNA
FDYWGQGTQVTVSSASTSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLS
WYQQKPGKAPKLLIWFGSRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
AQAGTHPTTFGQGTKVEIKR 146451.doc -75- 201042039 胺基酸加核苷酸加myc標籤序列（SEQ ID NO: 324)
EVQLLESGGGLVQPGGSLRLSCAASGFTFNRYSMGWLRQAPGKGLEWVSRIDS
YGRGTYYEDPVKGRFSISRDNSKNTLYLQMNSLRAEDTAVYYCAKISQFGSNA
FDYWGQGTQVTVSSASTSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTTLS
WYQQKPGKAPKLLIWFGSRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
AQAGTHPTTFGQGTKVEIKRAAAEQKLISEEDLN 核苷酸序列（SEQ ID NO: 325)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATAGGTATAGTATGG
GGTGGCTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTG
ATTCTTATGGTCGTGGTACATACTACGAAGACCCCGTGAAGGGCCGGTTCA
GCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC
TGCGTGCCGAGGACACCGCCGTATATTACTGTGCGAAAATTTCTCAGTTTGG
GTCAAATGCGTTTGACTACTGGGGTCAGGGAACCCAGGTCACCGTCTCGAG
CGCTAGCACCAGTGGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCC
CTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTC
CGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCTGGTTTGGTTCCCGGTTGCAAAGTGGGGTCCCATCACGTTT
CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCA
ACCTGAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACG
ACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG 核苷酸加myc標籤序列（SEQ ID NO: 326)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATAGGTATAGTATGG
GGTGGCTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTG
ATTCTTATGGTCGTGGTACATACTACGAAGACCCCGTGAAGGGCCGGTTCA
GCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC
TGCGTGCCGAGGACACCGCCGTATATTACTGTGCGAAAATTTCTCAGTTTGG
GTCAAATGCGTTTGACTACTGGGGTCAGGGAACCCAGGTCACCGTCTCGAG
CGCTAGCACCAGTGGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCC
CTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTC
CGATTGGGACGACGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCTGGTTTGGTTCCCGGTTGCAAAGTGGGGTCCCATCACGTTT
CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCA
ACCTGAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACG
ACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGGGCGGCCGCAGAACA
AAAACTCATCTCAGAAGAGGATCTGAATTAA DOM7h-ll-12/DOMlm-21-23融合物 DMS編號 5516 胺基酸序列（SEQ ID NO: 3 27)
EVQLLESGGGLVQPGGSLRLSCAASGFTFNRYSMGWLRQAPGKGLEWVSRIDS
YGRGTYYEDPVKGRFSISRDNSKNTLYLQMNSLRAEDTAYYYCAKISQFGSNA 146451.doc -76- 201042039
FDYWGQGTQVTVSSASTSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLS
WYQQKPGKAPKLLILFGSRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCA
QAGTHPTTFGQGTKVEIKR 胺基酸加核苷酸加myc標籤序列（SEQ ID NO: 328)
EYQLLESGGGLVQPGGSLRLSCAASGFTFNRYSMGWLRQAPGKGLEWVSRIDS
YGRGTYYEDPVKGRFSISRDNSKNTLYLQMNSLRAEDTAVYYCAKISQFGSNA
FDYWGQGTQVTYSSASTSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLS
WYQQKPGKAPKLLILFGSRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCA
QAGTHPTTFGQGTKVEIKRAAAEQKLISEEDLN 核苷酸序列（SEQ ID NO: 329)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATAGGTATAGTATGG ❹
GGTGGCTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTG
ATTCTTATGGTCGTGGTACATACTACGAAGACCCCGTGAAGGGCCGGTTCA
GCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC
TGCGTGCCGAGGACACCGCCGTATATTACTGTGCGAAAATTTCTCAGTTTGG
GTCAAATGCGTTTGACTACTGGGGTCAGGGAACCCAGGTCACCGTCTCGAG
CGCTAGCACCAGTGGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCC
CTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTC
CGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCTTGTTTGGTTCCCGGTTGCAAAGTGGGGTCCCATCACGTTT
CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCA
ACCTGAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACG
ACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG 核苷酸加myc標籤序列（SEQ ID NO: 33 0)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATAGGTATAGTATGG
GGTGGCTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTG
ATTCTTATGGTCGTGGTACATACTACGAAGACCCCGTGAAGGGCCGGTTCA
GCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC
TGCGTGCCGAGGACACCGCCGTATATTACTGTGCGAAAATTTCTCAGTTTGG
GTCAAATGCGTTTGACTACTGGGGTCAGGGAACCCAGGTCACCGTCTCGAG
CGCTAGCACCAGTGGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCC
CTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTC
CGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCTTGTTTGGTTCCCGGTTGCAAAGTGGGGTCCCATCACGTTT
CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCA
ACCTGAAGATTTTGCTACGTACTACTGTGCGCAGGCTGGGACGCATCCTACG
ACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGGGCGGCCGCAGAACA
AAAACTCATCTCAGAAGAGGATCTGAATTAA DOM7h-ll-15/DOMlm-21-23融合物 DMS編號 5517 胺基酸序列（SEQ ID NO: 331) 146451.doc -77- 201042039
EVQLLESGGGLVQPGGSLRLSCAASGFTFNRYSMGWLRQAPGKGLEWVSRIDS
YGRGTYYEDPVKGRFSISRDNSKNTLYLQMNSLRAEDTAVYYCAKISQFGSNA
FDYWGQGTQVTVSSASTSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLS
WYQQKPGKAPKLLILAFSRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCA
QAGTHPTTFGQGTKVEIKR 胺基酸加核苷酸加myc標籤序列（SEQ ID NO: 332)
EVQLLESGGGLYQPGGSLRLSCAASGFTFNRYSMGWLRQAPGKGLEWVSRIDS
YGRGTYYEDPVKGRFSISRDNSKNTLYLQMNSLRAEDTAVYYCAKISQFGSNA
FDYWGQGTQVTVSSASTSGPSDIQMTQSPSSLSASVGDRVTITCRASRPIGTMLS
WYQQKPGKAPKLLILAFSRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCA
QAGTHPTTFGQGTKVEIKRAAAEQKLISEEDLN 核苷酸序列（SEQ ID NO: 3 33)
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATAGGTATAGTATGG
GGTGGCTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTG
ATTCTTATGGTCGTGGTACATACTACGAAGACCCCGTGAAGGGCCGGTTCA
GCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC
TGCGTGCCGAGGACACCGCCGTATATTACTGTGCGAAAATTTCTCAGTTTGG
GTCAAATGCGTTTGACTACTGGGGTCAGGGAACCCAGGTCACCGTCTCGAG
CGCTAGCACCAGTGGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCC
CTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTC
CGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGTTTC
AGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGA
CGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGG 核苷酸加myc標籤序列（SEQ ID NO: 334) o
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCC
CTGCGTCTCTCCTGTGCAGCCTCCGGATTCACCTTTAATAGGTATAGTATGGG
GTGGCTCCGCCAGGCTCCAGGGAAGGGTCTAGAGTGGGTCTCACGGATTG
ATTCTTATGGTCGTGGTACATACTACGAAGACCCCGTGAAGGGCCGGTTCA
GCATCTCCCGCGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCC
TGCGTGCCGAGGACACCGCCGTATATTACTGTGCGAAAATTTCTCAGTTTGG
GTCAAATGCGTTTGACTACTGGGGTCAGGGAACCCAGGTCACCGTCTCGAG
CGCTAGCACCAGTGGTCCATCGGACATCCAGATGACCCAGTCTCCATCCTCC
CTGTCTGCATCTGTAGGAGACCGTGTCACCATCACTTGCCGGGCAAGTCGTC
CGATTGGGACGATGTTAAGTTGGTACCAGCAGAAACCAGGGAAAGCCCCTA
AGCTCCTGATCCTTGCTTTTTCCCGTTTGCAAAGTGGGGTCCCATCACGTTTC
AGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAA
CCTGAAGATTTTGCTACGTACTACTGCGCGCAGGCTGGGACGCATCCTACGA
CGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGGGCGGCCGCAGAACAA
AAACTCATCTCAGAAGAGGATCTGAATTAA 其中經my c標籤標記之分子指示於此表中，其為實例中 146451.doc -78- 201042039 PK研究中所用之型式。其中得到未經myc標籤標記之分 子，實例中之PK研究未用經myc標籤標記之物質來進行， 亦即以所示未經myc標籤標記之構築體進行研究。 例證
實驗部分中之所有編號均係根據Kabat(Kabat，E.A. National Institutes of Health (US) & Columbia University. Sequences of proteins of immunological interst，第 5版（US
Dept. Of Health and Human Services Public Health Service, National Institues of Health, Bethesda，MD，1991))。 描述DOM7h-ll及DOM7h-14變體之獲得。DOM7h-14變 體並不符合本發明。 實例1 : Vk親和力成熟 選擇物： HSA(人類血清白蛋白）及RSA(大鼠血清白蛋白）抗原係獲 自Sigma(基本上無脂肪酸，約99%(瓊脂糖凝膠電泳）、凍 乾粉末目錄號分別為A3 782及A6414)。 以上兩種抗原之生物素標記產物係藉由使用EZ連接磺 基-NHS-SS-生物素（Pierce,目錄號21331)製得。藉由使樣 品兩次穿過PD10脫鹽管柱，接著以lOOOx過量體積之PBS 在4°C下透析隔夜來移除無生物素試劑。藉由質譜法測試 所得產物且觀測到每個分子中含1 -2個生物素。 親和力成熟文庫： 使用 DOM7h-ll 及 DOM7h-14 親本 dAb(關於 DOM7h-ll 及 DOM7h-14之序列，請參看WO 2008/096158)產生易錯文庫 146451.doc • 79· 201042039 與CDR文庫。在pDOM4載體中產生CDR文庫且在pDOM33 載體中產生易錯文庫（以允許在經或未經蛋白酶處理下進 行選擇）。載體PDOM4為Fd噬菌體載體之衍生物，其中羞 冱///信號肽序列經酵母糖脂錨泊表面蛋白（GAS)信號肽置 換。其在前導序列與差诼之間亦含有標籤，其再 使差涿///處於閱讀框中。此前導序列在噬菌體呈現載體以 及其他原核表現載體中均良好起作用且可普遍使用。 pDOM33為pDOM4載體之經修飾型式，其中已移除c-myc 標籤，致使dAb-嗤菌體融合物對蛋白酶腺蛋白酶具有抗 性。此允許在噬菌體選擇中使用胰蛋白酶來選擇更具蛋白 酶穩定性之dAb(參看WO 2008149143)。 對於易錯成熟文庫，使用GENEMORPH® II隨機突變誘 發套組（隨機、獨特突變誘發套組，Stratagene)藉由PCR來 擴增編碼待成熟dAb之質體DNA。以5«/ I及iVoi I消化產物 且與已切開之噬菌體載體PDOM33進行連接反應。 對於CDR文庫，使用含有NNK或NNS密碼子之簡幷寡核 苷酸進行PCR反應以使待親和力成熟之dAb中之所需位置 多樣化。接著使用組裝PCR(Assembly PCR)來產生全長多 樣化插入物。以W I及I消化插入物且與pDOM4(用於 對多個殘基進行突變誘發）及pD0M5(用於對單一殘基進行 突變誘發）進行連接反應。pD0M5載體為基於pUC119之表 現載體，其中蛋白質表現由LacZ啟動子驅動。GAS1前導 序列（參看WO 2005/093074)確保使經分離之可溶dAb分泌 至大腸桿菌（五.coH)之周質及培養物上清液中。將dAb選殖 146451.doc •80· 201042039 至此載體之Sall/Notl中，其使dAb之C末端附上myc標籤。 使用*Sa/ /及/之此方案使得在N末端納入ST胺基酸序 列0 接著藉由電穿孔使用藉由任一方法產生之連接物轉型大 腸桿菌菌株ΤΒ1，並將經轉型細胞塗鋪於含有15 pg/ml四 環素（tetracycline)之2xTY璦脂上，產生> 5x1 07個純系之文 庫大小。 易錯文庫具有以下平均突變率及大小：DOM7h-ll(每個 〇 dAb中產生2.5個突變），大小：6.1X108，DOM7h-14(每個 dAb中產生2.9個突變），大小：5_4χ108。 各CDR文庫具有四種胺基酸多樣性。對於CDR 1及3各產 生兩個文庫，且對於CDR2產生一個文庫。各文庫中多樣 化之位置係如下（基於VK虛設DPK9序列之胺基酸）： 文庫大小 DOM7h-14 5.8xl07 4.2χ108 2.4χ108 2.5xl08 3.3χ108 DOM7h-ll 1 - Q27、S28、S30、S31(CDR1) 8.8><107
2 - S30、S3 卜 Y32、N34(CDR1) 4.6><108 3 - Y49 ' A50 Ά51 ' S53(CDR2) 3.9xl08 4 - Q89 ' S91 ' Y92 > S93(CDR3) 1.8x10s 5 - Y92、Y93、T94、N96(CDR3) 4.〇χ108 實例2 :選擇策略： 對於Vk AlbudAb™(抗血清白蛋白dAb)親和力成熟採用 三種噬菌體選擇策略： 1)僅針對HSA選擇： 進行三輪針對HSA之選擇。在所有輪中易錯文庫及各 CDR文庫均選擇為個別池。針對以1 mg/ml被動塗布於免 146451.doc -81 - 201042039 疫管上之HSA進行第一輪選擇。針對100 nM HSA進行第2 輪且針對10 nM(CDR選擇物）或20 nM或100 nM(易錯選擇 物）HSA(均呈可溶選擇物形式）進行第3輪，接著以易錯文 庫針對1.5 nM HSA(呈可溶選擇物形式）來進行第四輪選 擇。以0.1 Μ甘胺酸（pH 2·0)溶離易錯文庫，隨後以1 Μ Tris(pH 8·0)中和，且以1 mg/ml胰蛋白酶溶離CDR文庫， 隨後感染至對數期TG1細胞中。將第三輪各選擇物次選殖 於pDOM5中以供篩選。可溶選擇物使用生物素標記之 HSA。 2) 針對HSA之胰蛋白酶選擇： 為選擇與親本純系相比蛋白酶抗性提高且生物物理特性 可能改良之dAb，在噬菌體選擇中使用胰蛋白酶（參看WO 2008149143)。進行四輪針對HSA之選擇。針對被動塗布 之1 mg/ml HSA在無胰蛋白酶下進行第一輪易錯文庫選 擇；針對被動塗布之1 mg/ml HSA，在20 pg/ml胰蛋白酶 下在37°C下進行第二輪歷時1小時；藉由使用生物素標記 HSA之可溶選擇物針對100 nM HSA在20 pg/ml或100 pg/ml 胰蛋白酶下在37°C下進行第三輪選擇歷時1小時。藉由使 用生物素標記HSA之可溶選擇物針對100 nM HSA在100 pg/ml胰蛋白酶下在37°C下進行最後一輪選擇隔夜。 3) 針對HSA(第1輪）及RSA(第2-4輪）之交叉選擇： 針對1 mg/ml被動塗布之HSA或1 μΜ HSA(可溶選擇物） 進行第一輪選擇，接著針對生物素標記之RSA(對於第1輪 濃度為1 μΜ、對於第2輪濃度為100 nm且對於第3輪濃度為 146451.doc -82- 201042039 2〇11^1、1〇11]^或111]^)進行另外三輪可溶選擇。 篩選策略及親和力測定： 在各情況下，在選擇之後，使用QIAfilter midiprep套組 (Qiagen)製備來自適當輪之選擇的噬菌體DNA池，使用限 制酶Sail及Notl消化DNA，並將增濃之V基因連接至 pDOM5(表現具有myc標籤之dAb可溶表現載體）之相應位 點中（參看PCT/EP2008/067789)。使用經連接DNA來電轉 型大腸桿菌HB 21 51細胞，接著使其在含有抗生素卡本西 f% 林（carbenicillin)之瓊脂培養盤上生長隔夜。個別地評估所 得菌落之抗原結合。在各情況下，藉由BIAcore™(表面電 漿共振）測試至少96個純系與HSA、CSA(獼猴血清白蛋 白）、MS A(小鼠血清白蛋白）及RSA之結合。MS A抗原係獲 自Sigma(基本上無脂肪酸，約99%(瓊脂糖凝膠電泳），凍 乾粉末目錄號A3559)且使用prometic藍色樹脂（Amersham) 自獼猴血清白蛋白純化CSA。在96孔培養盤中在ONEX培 養基（Novagen)中在細菌培養物中在37°C下製備可溶dAb片 段隔夜。離心含有可溶dAb之培養物上清液且藉由BIAcore 分析其與高密度HSA、CSA、MSA及RSA CM5晶片之結 合。藉由解離速率篩選發現純系與所有此等物種之血清白 蛋白結合。對純系進行定序，揭示獨特dAb序列。 所選純系與親本之最小一致性（在胺基酸層面）為 97.2%(DOM7h-ll-3 : 97.2〇/〇，DOM7h-ll-12 : 98.2%， DOM7hll-15 ： 96.3% > DOM7h-ll-18 ： 98.2% » DOM7h-11-19 : 97.2%)。 146451.doc -83 - 201042039 所選純系與親本之最小一致性（在胺基酸層面）為 96.3%(DOM7h-14-l〇 : 96.3%，DOM7h-14-18 : 96.3%， DOM7h-14-19:98.2%，DOM7h-14-28:99.1%，DOM7h-14-36 : 97.2%) ° 在30°C下在250 rpm下在2.5 L搖瓶中之Onex培養基中使 獨特dAb以細菌上清液形式表現48小時。藉由吸收至蛋白 質L瓊脂糖，接著以10 mM甘胺酸（pH 2.0)溶離，從而自培 養基純化dAb。使用3種濃度1 μΜ、500 nM及50 nM之經純 化蛋白質藉由BIAcore證實與HSA、CSA、MSA及RSA之結 合。為測定AlbudAbs對各血清白蛋白之結合親和力（KD); 藉由 BIAcore，涵蓋 5000 nM 至 39 nM(5000 nM、2500 nM、1250 nM、625 nM、312 nM、156 nM、78nM、39 nM)之白蛋白濃度範圍來分析經純化之dAb。 表6
AlbudAb 對SA之親和力 (Κ〇)(ηΜ) Kd Ka 大鼠 DOM7h-14 60 2.095E-01 4.00E+06 DOM7h-14-10 4 9.640E-03 4.57E+06 DOM7h-14-18 410 2.275E-01 5.60E+05 DOM 7h-14-19 890 2.870E-01 3.20E+05 DOM 7h-14-28 45(140) 7.0E-02 (l_141e-l) 2.10E+06 (8.3e5) DOM 7h-14-36 30(6120) 2.9E-02 (5.54e-2) 1.55E+06 (9e3) DOM 7h-ll 2100 1.00E-01 4.80E+04 DOM 7h-ll-3 10000(88000) (7.18e-l) (8.11e3) DOM 7h-ll-12 200 5.22E-01 2.76E+06 DOM 7h-ll-15 20 2.10E-02 1.10E+06 DOM 7h-ll-18 80(29000) 6.0E-02 (3-7e-l) 1.64E+06 (1.3e4) DOM 7h-ll-19 28(17000) 9.1e-02 (1.4e_l) 9.80E+05 (8.1e3) 146451.doc -84- 201042039 犬 DOM 7h-14 66 9.65E-02 1.50E+06 DOM 7h-14-10 9 1.15E-02 1.60E+06 DOM 7h-14-18 180 1.05E-01 6.30E+5 DOM 7h-14-19 225 1.56E-01 7.00E+05 DOM 7h-14-28 66(136) 1.3E-01 (1.34e-l) 2.50E+06 (9.8e5) DOM 7h-14-36 35^7830) 1.9E-02 (l.le-1) 9.80E+06 (1.43e4) DOM 7h-ll 1000 6.82E-01 8.00E+05 DOM 7h-ll-3 670(200) 9.6E-02 (1.5e-l) 2.90E+05 (7.26e5) DOM 7h-ll-12 >6000 DOM 7h-ll-15 3 5.57E-03 5.80E+06 DOM 7h-ll-18 10000 (65000) 1.36 (4.8e-l) 2.25E+05 (7.3e3) DOM 7h-ll-19 >10000 (375000) (6.2e-l) (1.7e3) 小鼠 DOM 7h-14 12 4.82E-02 4.10E+06 DOM 7h-14-10 30 3.41E-02 1.29E+06 DOM 7h-14-18 65 9.24E-02 2.28E+06 DOM 7h-14-19 60 5.76E-02 1.16E+06 DOM 7h-14-28 26(31) 3.4E-02 (7.15e-2) 1.60E+06 (2.28e6) DOM 7h-14-36 35(33) 2.3E-02 (7.06e-2) 8.70E+05 (2.11e6) DOM 7h-ll 5000 9.00E-01 DOM 7h-ll-3 > 10000(36000) (6.12e-l) (1.67e4) DOM 7h-ll-12 130 1.89E-01 1.53E+06 DOM 7h-ll-15 10 9.40E-03 1.10E+06 DOM 7h-ll-18 150(1600) 2.4E-02 (6.23e-2) 4.40E+05 (4e4) DOM 7h-ll-19 100(18000) 3.7E-02 (8.8e-2) 1.40E+06 (4.9e3) 人類 DOM 7h-14 33 4.17E-02 1.43E+06 DOM 7h-14-10 12 1.39E-02 1.50E+06 DOM 7h-14-18 280 3.39E-02 1.89E+05 DOM 7h-14-19 70 5.25E-02 8.26E+05 DOM 7h-14-28 30(8260) 3.3E-02 (5.6e-2) 1.24E+06 (6.78e3) DOM 7h-14-36 28(1260) 2.4E-02 (6.7e-2) 1.23E+06 (5.4e4) 146451.doc •85- 201042039 DOM 7h-ll 2800 6.41E-01 7.00E+05 DOM 7h-ll-3 32(130) 1.6E-02 (2.35e-2) 6.50E+05 (1.86e5) DOM 7h-ll-12 350 4.13E-01 1.26E+06 DOM 7h-ll-15 1 1.84E-03 2.00E+06 DOM 7h-ll-18 36(32000) 5.1E-02 (2.7e-l) 3.40E+06 (8.39e3) DOM 7h-ll-19 65(38000) 1.1E-01 (2.09e-l) 1.80E+06 (5.4e3) * :括號中之值係來源於第二個獨立SPR實驗。 所有DOM7h-14來源之變體均對小鼠、大鼠、人類及犬 血清白蛋白具有交叉反應性。DOM7h-14-10與親本相比具 有改良之對大鼠、犬及人類血清白蛋白之親和力。 DOM7h-14-28具有改良之對RSA之親和力。DOM7h-14-36 具有改良之對RS A、CS A及MSA之親和力。 DOM7h-ll-3具有改良之對CSA及HSA之親和力。 DOM7h-ll-12具有改良之對RSA、MSA及HSA之親和力。 DOM7h-ll-15具有改良之對RSA、MSA、CSA及HSA之親 和力。DOM7h-ll-18及DOM7h-ll-19具有改良之對RSA、 MSA及HSA之親和力。 實例3 :關鍵DOM7h-ll譜系純系之來源： DOM7h-ll-3 :來自針對HSA，使用CDR2文庫（Y49、 A50、A51、S53)，第3輪輸出10 nM HSA進行之親和力成 熟 DOM7h-ll-12 :來自針對HSA，使用易錯文庫，第3輪 輸出（100 nM，HSA)在100 pg/ml胰蛋白酶下進行之親和力 成熟。 DOM7h-ll-15 :來自針對HSA作為第1輪，接著另外3輪 146451.doc -86- 201042039 選擇針對RSA、使用CDR2文庫（Y49、A50、A51、S53)且 於第3輪選擇存在InM RSA進行之交叉選擇。 DOM7h-ll-18 :來自針對HSA作為第1輪，接著另外3輪 選擇針對RSA、使用易錯文庫且第3輪輸出為20 nM RSA進 行之交叉選擇。 DOM7h-ll-19 :來自針對HSA作為第1輪，接著另外3輪 選擇針對RSA、使用易錯文庫且第3輪輸出為5 nM RSA進 行之交叉選擇。 〇 表7 : CDR序列（根據Kabat ;參考如上）
AlbudAb CDR CDR1 CDR2 CDR3 DPK9 Vk虚設 SQSISSYLN (SEQ ID NO: 335) YAASSLQS (SEQ ID NO: 336) QQSYSTPNT (SEQ ID NO: 337) DOM7h-ll SRPIGTTLS (SEQ ID NO: 338) WFGSRLQS (SEQ ID NO: 339) AQAGTHPTT (SEQ ID NO: 340) DOM7h-ll-12 SRPIGTMLS (SEQ ID NO: 341) LFGSRLQS (SEQ ID NO: 342) AQAGTHPTT (SEQ ID NO: 343) DOM 7h-1115 SRPIGTMLS (SEQ ID NO: 344) LAFSRLQS (SEQ ID NO: 345) AQAGTHPTT (SEQ ID NO: 346) DOM 7h-ll-18 SRPIGTMLS (SEQ ID NO: 347) WFGSRLQS (SEQ ID NO: 348) AQAGTHPTT (SEQ ID NO: 349) DOM 7h-ll-19 SRPIGTMLS (SEQ ID NO: 350) LFGSRLQS (SEQ ID NO: 351) AQTGTHPTT (SEQ ID NO: 352) DOM 7h-ll-3 SRPIGTTLS (SEQ ID NO: 353) LWFSRLQS (SEQ ID NO: 354) AQAGTHPTT (SEQ ID NO: 355) 實例4 :關鍵DOM7h-14譜系純系之來源： DOM7h-14-19 :來自針對HSA，使用易錯文庫，第3輪 輸出（100 nM，HSA)在100 pg/ml胰蛋白酶下進行之親和力 146451.doc -87- 201042039 成熟。 DOM7h-14-10 、 DOM7h-14-18 、 DOM7h-14-28 、 DOM7h-14-36 :來自針對 HSA，使用 CDR3 文庫（Y92、 Y93、T94、N96)、第3輪輸出進行之親和力成熟。 表8: CDR序列（根據Kabat;參考如上）
AlbudAb CDR CDR1 CDR2 CDR3 DPK9 Vk虛設 SQSISSYLN YAASSLQS QQSYSTPNT (SEQIDNO.-335) (SEQ ID NO: 336) (SEQ ID NO: 337) DOM 7h-14 SQWIGSQLS MWRSSLQS AQGAALPRT (SE〇 ID NO: 356) (SEQ ID NO: 357) (SEQ ID NO: 358) DOM 7h-14-10 SQWIGSQLS MWRSSLQS AQGLRHPKT (SEQ ID NO: 359) (SEQ ID NO: 360) (SEQ ID NO: 361) DOM 7h-14-18 SQWIGSQLS MWRSSLQS AQGLMKPMT (SEQ ID NO:362) (SEQ ID NO: 363) (SEQ ID NO: 364) DOM 7h-14-19 SQWIGSQLS MWRSSLQS AQGAALPRT (SEQ ID NO: 365) (SEQ ID NO: 366) (SEQ ID NO: 367) DOM 7h-14-28 SQWIGSQLS MWRSSLQS AQGAALPKT (SEQ ID NO: 368) (SEQ ID NO: 369) (SEQ ID NO: 370) DOM 7h-14-36 SQWIGSQLS MWRSSLQS AQGFKKPRT (SEQ ID NO: 371) (SEQ ID NO: 372) (SEQ ID NO: 373) 實例5:表現及生物物理表徵： 在30°C下在250 rpm下在Onex培養基中培養48小時之後 測定2.5 L搖瓶中之常規細菌表現量。藉由SEC MALLS及 D S C測定生物物理特徵。 SEC MALLS(尺寸排阻層析法連同多角度雷射光散射）為 表徵溶液中大分子之非侵入性技術。簡言之，根據蛋白質 之流體動力學特性，藉由尺寸排阻層析法（管柱：來自 146451.doc -88· 201042039 TOSOH Biosciences之 TSK3000 ;來自 Pharmacia之 S200)以 0.5 ml/min分離在缓衝液杜貝可（Dulbecco's)PBS中濃度為1 mg/mL之蛋白質。在分離之後，使用多角度雷射光散射 (MALLS)偵測器來量測蛋白質使光散射之傾向。隨角度而 變量測蛋白質穿過偵測器時散射光之強度。此量測值與使 用折射率（RI)偵測器測定之蛋白質濃度結合在一起允許使 用適當等式（分析軟體Astra ν·5.3.4.12之組成部分）計算莫 耳質量。
D S C (差示掃描熱量測定）：簡言之，以1 8 0 °C /小時之十亙 定速率加熱蛋白質（PBS中1 mg/mL)且量測與熱變性相關之 可偵測熱交換。測定轉變中點（appTm)，其係描述為50%蛋 白質呈其原生構形且其他50%變性之溫度。在此處，DSC 測定表觀轉變中點（appTm)，因為大部分所檢驗之蛋白質並 未完全再摺疊。Tm愈高，分子愈穩定。藉由非2態等式分 析伸展曲線。所用軟體套件為OriginR V7.0383。 表9
AlbudAb 生物物理參數 SEC MALLS DSCTmfC) DOM7h-14 M 60 DOM 7h-14-10 M 59 DOM 7h-14-18 M 58 DOM 7h-14-19 .M 59 DOM 7h l4-28 M 58.3/60.2 DOM 7h-14-36 M 59.2 DOM 7h-ll M 66.9-72.2 DOM 7h-ll-3 M(95%)* 66.6/70.5 146451.doc -89- 201042039 DOM 7h-ll-12 M(< 2%D) 71.7 DOM 7h-ll-15 M(< 5%D) 58.5-60.5 DOM 7h-ll-18 M(98%) 58.9/65.8 DOM 7h-ll-19 M 71.8/76.6 *在另一試驗中，單體儘管低於95%，但在SEC MALLS中 仍為主要所見之物質 吾人觀察到表9中所有純系在大腸桿菌中之表現量均在 15至119 mg/L之範圍内。 對於DOM7h-14及DOM7h-ll變體，在親和力成熟期間保 持有利生物物理參數（如藉由SEC MALLs所測定，在溶液 中為單體且如藉由DSC所測定，appTm > 55°C)及表現量。 單體狀態為有利的，因為其避免二聚化及產物可能會交聯 諸如細胞-表面受體之目標的風險。 實例6 :測定大鼠、小鼠及獼猴中之血清半衰期 WAlbudAbDOM7h-14_10、DOM7h-14-18、DOM7h-14-19、DOM7h-ll、D〇M7hll-12 及 DOM7h-ll-15 選殖於 pDOM5載體中。對於各AlbudAbTM，在大腸桿菌中表現20-5 0 mg之量且使用蛋白質L親和力樹脂自細菌培養物上清液 中純化，並以100 mM甘胺酸（pH 2)溶離。將蛋白質濃縮至 大於1 mg/ml，緩衝液交換於PBS中且使用Q旋轉管柱 (¥^38(^1106)耗盡内毒素。為進行大鼠藥物動力學（？1〇分 析，以單次靜脈内注射形式以2.5 mg/kg給予AlbudAb，每 種化合物使用3隻大鼠。在0.16、1、4、12、24、48、 72、120、1 68小時取血清樣品。按照下文所述之方法藉由 抗myc ELISA來分析血清含量。 146451.doc -90- 201042039 對於小鼠ΡΚ，以單次靜脈内注射形式以2.5 mg/kg對每 劑量組之3個個體給予DOM7h-ll、DOM7hll-12&D〇M7h-11 -15，且在10分鐘；1小時；8小時；24小時；48小時； 72小時；96小時取血清樣品。按照下文所述之方法藉由抗 myc ELISA來分析血清含量。 對於獼猴PK，以單次靜脈内注射形式以2·5 mg/kg對每 劑量組之3隻雌性獼猴給予DOM7h-14-10及DOM7h-ll-15，且在 0.083、0·25、0.5、1、2、4、8、24、48、96、 〇 144、192、288、336、504小時取血清樣品。按照下文所 述之方法藉由抗myc ELISA來分析血清含量。 抗myc ELISA方法 藉由抗myc ELISA量測血清中之AlbudAb濃度。簡言 之，將山羊抗myc多株抗體（1:500 ; Abeam，目錄號 ab9132)塗布於Nunc 96孔Maxisorp培養盤上隔夜且以5% BSA/PBS + 1%吐溫（tween)阻斷。以一系列與已知濃度之 標準並列的稀釋度添加血清樣品。接著依次使用兔多株抗
Q
Vk(l:l 000 ;自製試劑，在使用之前彙集血液且經蛋白質A 純化）及抗兔IgG HRP抗體（1:10,000 ; Sigma，目錄號 A2074)來彳貞測所結合之經myc標籤標記之AlbudAb。在各 檢定階段之間依次以3XPBS+0.1%吐溫20及3xPBS洗滌培養 盤。在最後一次洗滌之後添加TMB(SureBlue TMB 1組份 微孔過氧化酶受質（SureBlue TMB 1-Component Microwell Peroxidase Substrat)，KPL，目錄號 52-00-00)並讓其顯 色。以1 M HC1停止此反應且接著使用450 nm下之吸收率 146451.doc -91 - 201042039 來量測信號。 自原始ELIS A資料，藉由内插法，相對於標準曲線，同 時考慮稀釋倍數來確定未知樣品之濃度。自重複值測定各 時點之平均濃度結果且輸入WinNonLin分析套件（例如5.1 版，可獲自 Pharsight Corp·, Mountain View, CA94040, USA)。使用非隔室模型擬合資料，其中藉由軟體估算PK 參數以得到終末半衰期。選擇給藥資訊及時點以反映各ΡΚ 概況之終末階段。 表 10 :單一 AlbudAbTM ΡΚ 物種 AlbudAb 白蛋白 KD(nM) PK參數 AUC hxpg/ml CL ml/h/kg tl/2 h Vz ml/kg 大鼠 DOM7h-14* 60 DOM7h-14-10 4 2134.6 1.2 42.1 71.2 DOM7h-14-18 410 617.3 4.1 38.4 228.1 DOM 7h-14-19 890 632.6 4.1 36.3 213.3 DOM 7h-ll 2100 320.1 7.8 23.3 263.9 DOM 7h-ll-12 200 398.7 6.4 35.5 321.2 DOM 7h-ll-15 20 843.4 3.0 30.3 130.7 小鼠 DOM 7h-ll 5000 304.7 8.2 18.3 216.8 DOM 7h-ll-12 130 646.6 3.9 43.9 244.8 DOM 7h-ll-15 10 499.2 5.0 33.7 243.4 犬 DOM 7h-14* 66 217.5 DOM 7h-14-10 9 6174.6 0.4 200.8 117.8 DOM 7h-ll* 3300 135.1 DOM 7h-ll-15 3 4195 0.6 198.1 170.3 *歷史資料 使用非隔室模型來擬合自大鼠、小鼠及獼猴研究獲得之 藥物動力學參數。關鍵詞：AUC :自給藥時間外推至無限 146451.doc -92- 201042039 獲得之曲線下面積；CL :清除率；tl/2 :血液濃度變為一 半之時間；Vz :基於終末階段之分布的體積。 DOM7h-ll 12及DOM7h-ll-15與親本相比在大鼠及小鼠 中具有改良之AUC及tl/2。DOM7h-ll-15與親本相比在犬 中亦具有改良之AUC及tl/2。此AUC/tl/2改良與對血清白 蛋白之活體外KD改良有關。 實例7 : AlbudAbTM IFN融合物 選殖及表現 除單一 AlbudAb外，亦將親和力成熟Vk Albudab與干擾 素a2b(IFNa2b)連接以確定融合蛋白是否保持了 AlbudAb之 適用PK。 干擾素a2b胺基酸序列： εϋυΡ(5ΤΗ8[(^ΚίαΧΜΙΧΑ(5ΜΚΙΙΙ8υ8(：ΕΚΟΚΗΟΡΟΡΡ()ΕΕΡΟΝ(3ΡρΚΑΕΤΙΡ VLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTET PLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRS KE (SEQ ID NO:374) 干擾素a2b核苷酸序列： 〇 TGTGATCTGCCTCAAACCCACAGCCTGGGTAGCAGGAGGACCTTGATGCTC CTGGCACAGATGAGGAGAATCTCTCTTTTCTCCTGCTTGAAGGACAGACATG ACTTTGGATTTCCCCAGGAGGAGTTTGGCAACCAGTTCCAAAAGGCTGAAA CCATCCCTGTCCTCCATGAGATGATCCAGCAGATCTTCAATCTCTTCAGCAC AAAGGACTCATCTGCTGCTTGGGATGAGACCCTCCTAGACAAATTCTACACT GAACTCTACCAGCAGCTGAATGACCTGGAAGCCTGTGTGATACAGGGGGTG GGGGTGACAGAGACTCCCCTGATGAAGGAGGACTCCATTCTGGCTGTGAGG AAATACTTCCAAAGAATCACTCTCTATCTGAAAGAGAAGAAATACAGCCCTT GTGCCTGGGAGGTTGTCAGAGCAGAAATCATGAGATCTTTTTCTTTGTCAA CAAACTTGCAAGAAAGTTTAAGAAGTAAGGAA (SEQ ID NO:375) 經由TVAAPS連接區域將IFNa2b與AlbudAb連接（參看 WO 2007085814)。藉由SOE-PCR(根據Horton等人，Gene， 77，第61頁（1989)之方法的單一重疊延伸）選殖構築體。使 146451.doc -93- 201042039 用在TVAAPS連接區域具有約15個鹼基對重疊之引子來分 別進行AlbudAb及IFN序列之PCR擴增。所用引子如下： .IFNa2b SOE 片段5' IFNa2b SOE 片段31
Vk SOE片段5丨 亦引入myc標籤之 Vk SOE片段3' GCCCGGATCCACCGGCTGTGATCTG(SEQ ID NO: 376)
GGAGGATGGAGACTGGGTCATCTGGATGTC(SEQ IDNO:377)
GACATCCAGATGACCCAGTCTCCATCCTCC(SEQ IDNO:378) GCGCAAGCTTTTATTAATTCAGATCCTCTTC TGAGATGAGTTTTTGTTCTGCGGCCGCCCGT TTGATTTCCACCTTGGTCCC(SEQ ID NO:379) 分別純化該等片段且隨後僅使用側接引子在SOE(單一重 疊延伸PCR延伸）反應中組裝。 IFNa2b SOE 片段5, 亦引入myc標籤之 Vk SOE片段3' GCCCGGATCCACCGGCTGTGATCTG(SEQ ID NO: 380) GCGCAAGCTTTTATTAATTCAGATCCTCTTC TGAGATGAGTTTTTGTTCTGCGGCCGCCCGT TTGATTTCCACCTTGGTCCC(SEQ ID NO:381) 使用限制酶BamHI及Hindlll消化組裝之PCR產物，且將 基因連接至pDOM50(—種哺乳動物表現載體，其為具有N 端V-J2-C小鼠IgG分泌前導序列以促進表現於細胞培養基 中之ρΤΤ5衍生物）中之相應位點。 前導序列（胺基酸）： METDTLLLWVLLLWVPGSTG (SEQ ID NO:382) 前導序列（核苷酸）： ATGGAGACCGACACCCTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCCGGA TCCACCGGGC (SEQ ID NO:383) 使用 QIAfilter megaprep(Qiagen)製備質體 DNA。使用 146451.doc -94· 201042039 293-Fectin將1 pg DNA/ml轉染至HEK293E細胞中且於無血 清培養基中生長。使蛋白質在培養物中表現5天且使用蛋 白質L親和力樹脂自培養物上清液純化，並以1 〇〇 mM甘胺 酸（pH 2)溶離。將蛋白質濃縮至大於1 mg/ml，緩衝液交換 至PBS中且使用Q旋轉管柱（Vivascience)耗盡内毒素。 表11 :有或無myc標籤之干擾素a2b-AlbudAb序列（胺基睃 序列及核苷酸序列形式） 干擾素a2b位於以下融合物中AlbudAb之N端。
aa + myc nt + myc 無線籤aa 無線籤nt DMS7321 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 14) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACVIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVYRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA TCRASQWIGSQLS ACTATTCCTGT SPCAWEVVR AACTATTCCTG WYQQKPGKAPKLL CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA IMWRSSLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA GAALPRTFGQGTK GGACTCATCAG SVGDRVTITC AGGACTCATCA VEIKR CCGCTTGGGAT RASQWIGSQL GCCGCTTGGGA aaAeqkliseedl GAAACTCTGTT SWYQQKPGK TGAAACTCTGT N* (SEQID AGATAAATTCT APKLLIMWR TAGATAAATTC NO:384) ACACTGAACTA SSLQSGVPSR TACACTGAACT 146451.doc -95· 201042039
TATCAACAACT FSGSGSGTDF ATATCAACAAC GAACGATCTAG TLTISSLQPED TGAACGATCTA AGGCTTGCGTT FATYYCAQG GAGGCTTGCGT ATTCAGGGTGT AALPRTFGQG TATTCAGGGTG AGGAGTTACTG TKVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT ATGAAAGAAGA NO:386) AATGAAAGAA TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG TATCACATTGTA CGTATCACATT TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG _ GGAGGTGGTTA CATGGGAGGTG GAGCAGAAATT GTTAGAGCAG ATGAGGTCCTT AAATTATGAGG CTCTCTTTCTA TCCTTCTCTCT CGAATTTGCAA TTCTACGAATT GAATCTTTGAG TGCAAGAATCT ATCTAAGGAAA TTGAGATCTAA CCGTCGCTGCT GGAAACCGTC CCATCTGACAT GCTGCTCCATC CCAGATGACCC TGACATCCAGA AGTCTCCATCC TGACCCAGTCT TCCCTGTCTGC CCATCCTCCCT ATCTGTAGGAG GTCTGCATCTG , ACCGTGTCACC TAGGAGACCGT ATCACTTGCCG GTCACCATCAC GGCAAGTCAGT TTGCCGGGCAA GGATTGGGTCT GTCAGTGGATT CAGTTATCTTG GGGTCTCAGTT GTACCAGCAGA ATCTTGGTACC AACCAGGGAA AGCAGAAACC AGCCCCTAAGC AGGGAAAGCC TCCTGATCATG CCTAAGCTCCT TGGCGTTCCTC GATCATGTGGC GTTGCAAAGTG GTTCCTCGTTG GGGTCCCATCA CAAAGTGGGG
Q 146451.doc -96- 201042039 Ο
CGTTTCAGTGG TCCCATCACGT CAGTGGATCTG TTCAGTGGCAG GGACAGATTTC TGGATCTGGGA ACTCTCACCAT CAGATTTCACT CAGCAGTCTGC CTCACCATCAG AACCTGAAGAT CAGTCTGCAAC TTTGCTACGTA CTGAAGATTTT CTACTGTGCTC GCTACGTACTA AGGGTGCGGC CTGTGCTCAGG GTTGCCTAGGA GTGCGGCGTTG CGTTCGGCCAA CCTAGGACGTT GGGACCAAGG CGGCCAAGGG TGGAAATCAAA ACCAAGGTGG CGGGCGGCCG AAATCAAACG CAGAACAAAA G (SEQID ACTCATCTCA NO:387) GAAGAGGATC TGAATTAA (SE〇IDNO:385) DMS732 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 14-10) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACVIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVVRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA TCRASQWIGSQLS ACTATTCCTGT SPCAWEVVR AACTATTCCTG WYQQKPGKAPKLL CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA IMWRSSLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA GLRHPKTFGQGTK GGACTCATCAG SVGDRVTITC AGGACTCATCA 146451.doc •97- 201042039
VEIKR CCGCTTGGGAT RASQWIGSQL GCCGCTTGGGA AAAEQKLISEEDL GAAACTCTGTT SWYQQKPGK TGAAACTCTGT N* (SEQID AGATAAATTCT APKLLIMWR TAGATAAATTC NO:388) ACACTGAACTA SSLQSGVPSR TACACTGAACT TATCAACAACT FSGSGSGTDF ATATCAACAAC GAACGATCTAG TLTISSLQPED TGAACGATCTA AGGCTTGCGTT FATYYCAQGL GAGGCTTGCGT ATTCAGGGTGT RHPKTFGQG TATTCAGGGTG AGGAGTTACTG TKVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT ATGAAAGAAGA NO:390) AATGAAAGAA TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG _ TATCACATTGTA CGTATCACATT TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG GGAGGTGGTTA CATGGGAGGTG GAGCAGAAATT GTTAGAGCAG ATGAGGTCCTT AAATTATGAGG CTCTCTTTCTA TCCTTCTCTCT CGAATTTGCAA TTCTACGAATT GAATCTTTGAG TGCAAGAATCT ATCTAAGGAAA TTGAGATCTAA CCGTCGCTGCT GGAAACCGTC CCATCTGACAT GCTGCTCCATC 丨 CCAGATGACCC TGACATCCAGA AGTCTCCATCC TGACCCAGTCT TCCCTGTCTGC CCATCCTCCCT ATCTGTAGGAG GTCTGCATCTG ACCGTGTCACC TAGGAGACCGT ATCACTTGCCG GTCACCATCAC GGCAAGTCAGT TTGCCGGGCAA GGATTGGGTCT GTCAGTGGATT CAGTTATCTTG GGGTCTCAGTT GTACCAGCAGA ATCTTGGTACC AACCAGGGAA AGCAGAAACC AGCCCCTAAGC AGGGAAAGCC I46451.doc -98- 201042039
TCCTGATCATG CCTAAGCTCCT TGGCGTTCCTC GATCATGTGGC GTTGCAAAGTG GTTCCTCGTTG GGGTCCCATCA CAAAGTGGGG CGTTTCAGTGG TCCCATCACGT CAGTGGATCTG TTCAGTGGCAG GGACAGATTTC TGGATCTGGGA ACTCTCACCAT CAGATTTCACT CAGCAGTCTGC CTCACCATCAG AACCTGAAGAT CAGTCTGCAAC TTTGCTACGTA CTGAAGATTTT CTACTGTGCTC GCTACGTACTA AGGGTTTGAGG CTGTGCTCAGG CATCCTAAGAC GTTTGAGGCAT GTTCGGCCAAG CCTAAGACGTT GGACCAAGGT CGGCCAAGGG GGAAATCAAAC ACCAAGGTGG GGGCGGCCGC AAATCAAACG AGAACAAAAA G (SEQID CTCATCTCAG NO:391) AAGAGGATCT GAATTAA (SE〇 ID NO:389) DMS7323 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 14-18) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACVIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVVRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA TCRASQWIGSQLS ACTATTCCTGT SPCAWEVVR AACTATTCCTG WYQQKPGKAPKLL CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA 146451.doc -99- 201042039
IMWRSSLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA GLMKPMTFGQGTK GGACTCATCAG SVGDRYTITC AGGACTCATCA VEIKRAAAEQKLIS CCGCTTGGGAT RASQWIGSQL GCCGCTTGGGA EEDLN* (SEQ ID GAAACTCTGTT SWYQQKPGK TGAAACTCTGT NO:392) AGATAAATTCT APKLLIMWR TAGATAAATTC ACACTGAACTA SSLQSGVPSR TACACTGAACT TATCAACAACT FSGSGSGTDF ATATCAACAAC GAACGATCTAG TLTISSLQPED TGAACGATCTA AGGCTTGCGTT FATYYCAQGL GAGGCTTGCGT ATTCAGGGTGT MKPMTFGQG TATTCAGGGTG AGGAGTTACTG TKVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT . ATGAAAGAAGA NO:394) AATGAAAGAA TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG TATCACATTGTA CGTATCACATT TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG GGAGGTGGTTA CATGGGAGGTG GAGCAGAAATT GTTAGAGCAG ATGAGGTCCTT AAATTATGAGG CTCTCTTTCTA TCCTTCTCTCT CGAATTTGCAA TTCTACGAATT 丨 GAATCTTTGAG TGCAAGAATCT ATCTAAGGAAA TTGAGATCTAA CCGTCGCTGCT GGAAACCGTC CCATCTGACAT GCTGCTCCATC CCAGATGACCC TGACATCCAGA AGTCTCCATCC TGACCCAGTCT TCCCTGTCTGC CCATCCTCCCT ATCTGTAGGAG GTCTGCATCTG ACCGTGTCACC TAGGAGACCGT ATCACTTGCCG GTCACCATCAC GGCAAGTCAGT TTGCCGGGCAA GGATTGGGTCT GTCAGTGGATT 146451.doc •100· 201042039
CAGTTATCTTG GGGTCTCAGTT GTACCAGCAGA ATCTTGGTACC AACCAGGGAA AGCAGAAACC AGCCCCTAAGC AGGGAAAGCC TCCTGATCATG CCTAAGCTCCT TGGCGTTCCTC GATCATGTGGC GTTGCAAAGTG GTTCCTCGTTG GGGTCCCATCA CAAAGTGGGG CGTTTCAGTGG TCCCATCACGT CAGTGGATCTG TTCAGTGGCAG GGACAGATTTC TGGATCTGGGA ACTCTCACCAT CAGATTTCACT CAGCAGTCTGC CTCACCATCAG AACCTGAAGAT CAGTCTGCAAC TTTGCTACGTA CTGAAGATTTT CTACTGTGCTC GCTACGTACTA AGGGTCTTATG CTGTGCTCAGG AAGCCTATGAC GTCTTATGAAG GTTCGGCCAAG CCTATGACGTT GGACCAAGGT CGGCCAAGGG GGAAATCAAAC ACCAAGGTGG - GGGCGGCCGC AAATCAAACG AGAACAAAAA G (SEQ ID CTCATCTCAG NO:395) AAGAGGATCT GAATTAA (SEQ IDNO:393) DMS7324 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 14-19) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACYIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVVRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG 146451.doc -101 - 201042039
ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA SCRASQWIGSQLS ACTATTCCTGT SPCAWEVVR AACTATTCCTG WYQQKPGEAPKLL CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA IMWRSSLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA GAALPRTFGQGTK GGACTCATCAG SVGDRVTISC AGGACTCATCA VEIKR CCGCTTGGGAT RASQWIGSQL GCCGCTTGGGA AAAEQKLISEEDL GAAACTCTGTT SWYQQKPGE TGAAACTCTGT N* (SEQ ID AGATAAATTCT APKLLIMWR TAGATAAATTC NO:396) ACACTGAACTA SSLQSGVPSR TACACTGAACT TATCAACAACT FSGSGSGTDF ATATCAACAAC GAACGATCTAG TLTISSLQPED TGAACGATCTA . AGGCTTGCGTT FATYYCAQG GAGGCTTGCGT ATTCAGGGTGT AALPRTFGQG TATTCAGGGTG AGGAGTTACTG TKVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT ATGAAAGAAGA NO:398) AATGAAAGAA TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG TATCACATTGTA CGTATCACATT TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG GGAGGTGGTTA CATGGGAGGTG j GAGCAGAAATT GTTAGAGCAG ATGAGGTCCTT AAATTATGAGG CTCTCTTTCTA TCCTTCTCTCT CGAATTTGCAA TTCTACGAATT GAATCTTTGAG TGCAAGAATCT ATCTAAGGAAA TTGAGATCTAA CCGTCGCTGCT GGAAACCGTC CCATCTGACAT GCTGCTCCATC CCAGATGACCC TGACATCCAGA AGTcTCCATCCT TGACCCAGTcT CCCTGTCTGCA CCATCCTCCCT TCTGTAGGAGA GTCTGCATCTG Ο ◎ 146451.doc -102- 201042039 Ο
CCGTGTCACCA TAGGAGACCGT TCTCTTGCCGG GTCACCATCTC GCAAGTCAGTG TTGCCGGGCAA GATTGGGTCTC GTCAGTGGATT AGTTATCTTGG GGGTCTCAGTT TACCAGCAGAA ATCTTGGTACC ACCAGGGGAA AGCAGAAACC GCCCCTAAGCT AGGGGAAGCC CCTGATCATGT CCTAAGCTCCT GGCGTTCCTCG GATCATGTGGC TTGCAAAGTGG GTTCCTCGTTG GGTCCCATCAC CAAAGTGGGG GTTTCAGTGGC TCCCATCACGT AGTGGATCTGG TTCAGTGGCAG GACAGATTTCA TGGATCTGGGA CTCTCACCATC CAGATTTCACT AGCAGTCTGCA CTCACCATCAG ACCTGAAGATT CAGTCTGCAAC TTGCTACGTAC CTGAAGATTTT TACTGTGCTCA GCTACGTACTA GGGTGCGGCGT CTGTGCTCAGG TGCCTAGGACG GTGCGGCGTTG TTCGGCCAAGG CCTAGGACGTT GACCAAGGTG CGGCCAAGGG GAAATCAAACG ACCAAGGTGG GGCGGCCGCA AAATCAAACG GAACAAAAAC G (SEQ ID TCATCTCAGA AGAGGATCTG AATTAA (SEQ ID NO:397) NO:399) DMS7325 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 11) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACVIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC 146451.doc -103- 201042039
LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVVRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA TCRASRPIGTTLSW ACTATTCCTGT SPCAWEVVR AACTATTCCTG YQQKPGKAPKLLI CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA WFGSRLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA AGTHPTTFGQGTK GGACTCATCAG SVGDRVTITC AGGACTCATCA VEIKR CCGCTTGGGAT RASRPIGTTL GCCGCTTGGGA AAAEQKLISEEDL GAAACTCTGTT SWYQQKPGK TGAAACTCTGT . N* (SEQ ID AGATAAATTCT APKLLIWFGS TAGATAAATTC N0.400) ACACTGAACTA RLQSGVPSRF TACACTGAACT TATCAACAACT SGSGSGTDFT ATATCAACAAC GAACGATCTAG LTISSLQPEDF TGAACGATCTA AGGCTTGCGTT ATYYCAQAG GAGGCTTGCGT ATTCAGGGTGT THPTTFGQGT TATTCAGGGTG AGGAGTTACTG KVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT ATGAAAGAAGA NO:402) AATGAAAGAA TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG TATCACATTGTA CGTATCACATT ([ TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG GGAGGTGGTTA CATGGGAGGTG GAGCAGAAATT GTTAGAGCAG ATGAGGTCCTT AAATTATGAGG CTCTCTTTCTA TCCTTCTCTCT CGAATTTGCAA TTCTACGAATT GAATCTTTGAG TGCAAGAATCT ATCTAAGGAAA TTGAGATCTAA CCGTCGCTGCT GGAAACCGTC CCATCTGACAT GCTGCTCCATC 146451.doc •104- 201042039
CCAGATGACCC TGACATCCAGA AGTCTCCATCC TGACCCAGTCT TCCCTGTCTGC CCATCCTCCCT ATCTGTAGGAG GTCTGCATCTG ACCGTGTCACC TAGGAGACCGT ATCACTTGCCG GTCACCATCAC GGCAAGTCGTC TTGCCGGGCAA CGATTGGGACG GTCGTCCGATT ACGTTAAGTTG GGGACGACGTT GTACCAGCAGA AAGTTGGTACC AACCAGGGAA AGCAGAAACC AGCCCCTAAGC AGGGAAAGCC TCCTGATCTGG CCTAAGCTCCT TTTGGTTCCCG GATCTGGTTTG GTTGCAAAGTG GTTCCCGGTTG GGGTCCCATCA CAAAGTGGGG CGTTTCAGTGG TCCCATCACGT CAGTGGATCTG TTCAGTGGCAG GGACAGATTTC TGGATCTGGGA ACTCTCACCAT CAGATTTCACT CAGCAGTCTGC CTCACCATCAG AACCTGAAGAT CAGTCTGCAAC TTTGCTACGTA CTGAAGATTTT CTACTGTGCGC GCTACGTACTA AGGCTGGGAC CTGTGCGCAGG GCATCCTACGA CTGGGACGCAT CGTTCGGCCAA CCTACGACGTT GGGACCAAGG CGGCCAAGGG TGGAAATCAAA ACCAAGGTGG CGGGCGGCCG AAATCAAACG CAGAACAAAA G (SEQ ID ACTCATCTCA NO-.403) GAAGAGGATC TGAATTAA (SEQ ID NO:401) DMS7326 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 11-12) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT 146451.doc -105· 201042039
LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACVIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVVRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA TCRASRPIGTMLS ACTATTCCTGT SPCAWEVVR AACTATTCCTG WYQQKPGKAPKLL CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA ILFGSRLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT , SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA AGTHPTTFGQGTK GGACTCATCAG SVGDRVTITC AGGACTCATCA VEIKR CCGCTTGGGAT RASRPIGTML GCCGCTTGGGA AAAEQKLISEEDL GAAACTCTGTT SWYQQKPGK TGAAACTCTGT Ν* (SEQ ID AGATAAATTCT APKLLILFGS TAGATAAATTC NO :404) ACACTGAACTA RLQSGVPSRF TACACTGAACT TATCAACAACT SGSGSGTDFT ATATCAACAAC GAACGATCTAG LTISSLQPEDF TGAACGATCTA AGGCTTGCGTT ATYYCAQAG GAGGCTTGCGT ATTCAGGGTGT THPTTFGQGT TATTCAGGGTG AGGAGTTACTG KVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT ATGAAAGAAGA NO:406) AATGAAAGAA j TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG TATCACATTGTA CGTATCACATT TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG GGAGGTGGTTA CATGGGAGGTG GAGCAGAAATT GTTAGAGCAG ATGAGGTCCTT AAATTATGAGG CTCTCTTTCTA TCCTTCTCTCT CGAATTTGCAA TTCTACGAATT Ο Ο 146451.doc 106· 201042039
GAATCTTTGAG ATCTAAGGAAA CCGTCGCTGCT CCATCTGACAT CCAGATGACCC AGTCTCCATCC TCCCTGTCTGC ATCTGTAGGAG ACCGTGTCACC ATCACTTGCCG GGCAAGTCGTC CGATTGGGACG ATGTTAAGTTG GTACCAGCAGA AACCAGGGAA AGCCCCTAAGC TCCTGATCTTG TTTGGTTCCCG GTTGCAAAGTG GGGTCCCATCA CGTTTCAGTGG CAGTGGATCTG GGACAGATTTC ACTCTCACCAT CAGCAGTCTGC AACCTGAAGAT TTTGCTACGTA CTACTGTGCGC AGGCTGGGAC GCATCCTACGA CGTTCGGCCAA GGGACCAAGG TGGAAATCAAA CGGGCGGCCG CAGAACAAAA ACTCATCTCA GAAGAGGATC TGAATTAA (SEQ ID NO:4Q5 TGCAAGAATCT TTGAGATCTAA GGAAACCGTC GCTGCTCCATC TGACATCCAGA TGACCCAGTCT CCATCCTCCCT GTCTGCATCTG TAGGAGACCGT GTCACCATCAC TTGCCGGGCAA GTCGTCCGATT GGGACGATGTT AAGTTGGTACC AGCAGAAACC AGGGAAAGCC CCTAAGCTCCT GATCTTGTTTG GTTCCCGGTTG CAAAGTGGGG TCCCATCACGT TTCAGTGGCAG TGGATCTGGGA CAGATTTCACT CTCACCATCAG CAGTCTGCAAC CTGAAGATTTT GCTACGTACTA CTGTGCGCAGG CTGGGACGCAT CCTACGACGTT CGGCCAAGGG ACCAAGGTGG AAATCAAACG G (SEQ ID NO:407) 146451.doc -107- 201042039
DMS7327 CDLPQTHSLGSRRT TGCGACTTGCC CDLPQTHSLG TGCGACTTGCC (IFNa2b- LMLLAQMRRISLFS ACAGACACATA SRRTLMLLA ACAGACACATA DOM7h- CLKDRHDFGFPQE GTTTGGGATCA QMRRISLFSC GTTTGGGATCA 11-15) EFGNQFQKAETIPV AGAAGAACATT LKDRHDFGFP AGAAGAACATT LHEMIQQIFNLFST GATGTTATTAG QEEFGNQFQ GATGTTATTAG KDSSAAWDETLLD CACAAATGCGT KAETIPVLHE CACAAATGCGT KFYTELYQQLNDL AGAATTTCTTT MIQQIFNLFS AGAATTTCTTT EACVIQGVGVTETP GTTCTCTTGTC TKDSSAAWD GTTCTCTTGTC LMKEDSILAVRKYF TAAAGGACCGT ETLLDKFYTE TAAAGGACCGT QRITLYLKEKKYSP CACGACTTCGG LYQQLNDLE CACGACTTCGG CAWEVVRAEIMRS ATTCCCTCAGG ACVIQGVGV ATTCCCTCAGG FSLSTNLQESLRSK AAGAGTTTGGA TETPLMKEDS AAGAGTTTGG ETVAAPSDIQMTQS AACCAATTCCA ILAVRKYFQR AAACCAATTCC PSSLSASVGDRVTI AAAAGCAGAA ITLYLKEKKY AAAAAGCAGA L TCRASRPIGTMLS ACTATTCCTGT SPCAWEVVR AACTATTCCTG WYQQKPGKAPKLL CTTGCACGAAA AEIMRSFSLS TCTTGCACGAA ILAFSRLQSGVPSR TGATCCAGCAA TNLQESLRSK ATGATCCAGCA FSGSGSGTDFTLTIS ATATTCAATTTG ETVAAPSDIQ AATATTCAATTT SLQPEDFATYYCAQ TTTTCTACAAA MTQSPSSLSA GTTTTCTACAA AGTHPTTFGQGTK GGACTCATCAG SVGDRVTITC AGGACTCATCA VEIKR CCGCTTGGGAT RASRPIGTML GCCGCTTGGGA AAAEQKLISEEDL GAAACTCTGTT SWYQQKPGK TGAAACTCTGT N* (SEQ ID AGATAAATTCT APKLLILAFS TAGATAAATTC NO.-408) ACACTGAACTA RLQSGVPSRF TACACTGAACT TATCAACAACT SGSGSGTDFT ATATCAACAAC GAACGATCTAG LTISSLQPEDF TGAACGATCTA AGGCTTGCGTT ATYYCAQAG GAGGCTTGCGT i ATTCAGGGTGT THPTTFGQGT TATTCAGGGTG AGGAGTTACTG KVEIKR TAGGAGTTACT AAACTCCCCTA (SEQ ID GAAACTCCCCT ATGAAAGAAGA NO:410) AATGAAAGAA TTCAATTCTAG GATTCAATTCT CCGTTAGAAAA AGCCGTTAGAA TACTTTCAGCG AATACTTTCAG TATCACATTGTA CGTATCACATT TTTAAAGGAAA GTATTTAAAGG AGAAATACTCC AAAAGAAATA CCATGTGCATG CTCCCCATGTG GGAGGTGGTTA CATGGGAGGTG ύ 146451.doc -108· 201042039
GAGCAGAAATT ATGAGGTCCTT CTCTCTTTCTA CGAATTTGCAA GAATCTTTGAG ATCTAAGGAAA CCGTCGCTGCT CCATCTGACAT CCAGATGACCC AGTCTCCATCC TCCCTGTCTGC ATCTGTAGGAG ACCGTGTCACC ATCACTTGCCG GGCAAGTCGTC CGATTGGGACG ATGTTAAGTTG GTACCAGCAGA AACCAGGGAA AGCCCCTAAGC TCCTGATCCTT GCTTTTTCCCG TTTGCAAAGTG GGGTCCCATCA CGTTTCAGTGG CAGTGGATCTG GGACAGATTTC ACTCTCACCAT CAGCAGTCTGC AACCTGAAGAT TTTGCTACGTA CTACTGCGCGC AGGCTGGGAC GCATCCTACGA CGTTCGGCCAA GGGACCAAGG TGGAAATCAAA CGGGCGGCCG CAGAACAAAA
GTTAGAGCAG AAATTATGAGG TCCTTCTCTCT TTCTACGAATT TGCAAGAATCT TTGAGATCTAA GGAAACCGTC GCTGCTCCATC TGACATCCAGA TGACCCAGTCT CCATCCTCCCT GTCTGCATCTG TAGGAGACCGT GTCACCATCAC TTGCCGGGCAA GTCGTCCGATT GGGACGATGTT AAGTTGGTACC AGCAGAAACC AGGGAAAGCC CCTAAGCTCCT GATCCTTGCTT TTTCCCGTTTG CAAAGTGGGG TCCCATCACGT TTCAGTGGCAG TGGATCTGGGA CAGATTTCACT CTCACCATCAG CAGTCTGCAAC CTGAAGATTTT GCTACGTACTA CTGCGCGCAG GCTGGGACGCA TCCTACGACGT TCGGCCAAGG GACCAAGGTG GAAATCAAAC GG (SEQID H6451.doc -109- 201042039 ACTCATCTCA GAAGAGGATC TGAATTAA (SEQ ID NO:409) NO:411) 以粗體突出之胺基酸及核苷酸序列表示選殖位點及MYC 標籤。*表示位於基因末端之終止密碼子。 親和力測定及生物物理表徵： 為測定AlbudAb-IFNa2b融合蛋白對各血清白蛋白之結合 親和力（KD);藉由白蛋白（藉由一級胺偶合於CM5晶片上來 固定；BIAcore)上之 BIAcore，使用 HBS-EP BIAcore 缓衝 液中 5000 nM至 39 nM(5000 nM、2500 nM、1250 nM、625 nM、312 nM、156 nM、78 nM、39 nM)之融合蛋白濃度來 分析經純化之融合蛋白。 表12 :對SA之親和力
AlbudAb 融合物 對SA之親和力 (nM) Kd Ka 大鼠 DOM7h-14 IFNa2b 350 4.500E-02 1.28E+05 DOM7h-14-10 IFNa2b 16 4.970E-03 5.90E+05 DOM 7h-14-18 IFNa2b 780 2.127E-01 5.80E+05 DOM 7h-14-19 IFNa2b 1900 1.206E-01 7.96E+04 DOM 7h-ll IFNa2b 6000 7.500E-01 nd DOM 7h-ll-12 IFNa2b 1700 3.100E-01 1.30E+05 DOM 7h-ll-15 IFNa2b 200 1.660E-02 1.50E+05 犬 DOM 7h-14 IFNa2b 60 1.32E-02 5.0E+05 DOM 7h-14-10 IFNa2b 19 7.05E-03 4.50E+05 DOM 7h-14-18 IFNa2b 不結合 不結合 不結合 DOM 7h-14-19 IFNa2b 520 8.47E-02 2.73E+05 DOM 7h-ll IFNa2b 3300 3.59E-01 1.20E+05 DOM 7h-ll-12 IFNa2b 630 3.45E-01 7.00E+05 DOM 7h-ll-15 IFNa2b 15 4.86E-03 3.60E+05 146451.doc -110- 201042039 Μ/D表示如藉由SEC MALLS所偵測到之單體/二聚體平衡 吾人觀察到對於表13中之所有純系，在HEK293中之表 現均在17.5至54 mg/L之範圍内。 對於 IFNa2b-DOM7h-14 及 IFNa2b-DOM7h-ll 變體，在親 和力成熟期間保持有利生物物理參數及表現量。 AlbudAb-IFNa2b融合物之PK測定
AlbudAbs IFNa2b ^ ^ DMS7321 (IFNa2b-DOM7h-14)、DMS7322(IFNa2b-DOM7h-14-10)、DMS7323(IFNa2b-O DOM7h-14-18)、DMS7324(IFNa2b-DOM7h-14-19)、DMS7325 (IFNa2b-DOM7h-ll) ' DMS7326(IFNa2b-DOM7h-11 -12) ' DMS7327(IFNa2b-DOM7h-ll-15)以 20-50 mg之量在 HEK293 細胞中與my c標籤一起表現且使用蛋白質L親和力樹脂自 培養物上清液純化，且以1〇〇 mM甘胺酸（pH 2)溶離。將蛋 白質濃縮至大於1 mg/ml，缓衝液交換至杜貝可PBS中且使 用Q旋轉管柱（Vivascience)耗盡内毒素。 為進行大鼠PK，以單次靜脈内注射形式以2.0 mg/kg給 ^ 予IFN-AlbudAb，每種化合物使用3隻大鼠。在0.16、1、 4、8、24、48、72、120、168小時取血清樣品。藉由 EASY ELISA，根據製造商說明書（GE Healthcare，目錄號 RPN5960)來分析血清含量。 為進行小鼠PK，所有具有myc標籤之DMS7322(IFN2b-DOM7h-14-10)、DMS7325(IFN2b-DOM7h-ll)、DMS7326 (IFN2b-DOM7h-ll-12)、DMS7327(IFN2b-DOM7h-ll-15)均 以單次靜脈内注射形式以2.0 mg/kg給予每劑量組之3個個 146451.doc 112- 201042039 小鼠 —- DOM 7h-14 IFNa2b 240 3.21ΕΌ2-- 1.50E+06 DOM 7h-14-10 IFNa2b 60 "3.45E^〇5-- 6.86E+05 DOM 7h-14-18 IFNa2b 180 1.5〇Ε^〇ϊ------ 9.84E+05 DOM 7h-14-19 IFNa2b 490 4.03El〇5 1.19E+05 DOM 7h-ll IFNa2b 6000 1.55E-01 nd DOM 7h-ll-12 IFNa2b 150 "9^9E^~ 6.30E+05 DOM 7h-ll-15 IFNa2b 28 6.69E-CH 2.80E+05 人類 DOM 7h-14 IFNa2b 244 2.21Εΐ〇5~ 9.89E+04 DOM 7h-14-10 IFNa2b 32 6.58Ε-ΓΠ 3.48E+05 DOM 7h-14-18 IFNa2b 470 "2?75E^〇I~~ 6.15E+05 DOM 7h-14-19 IFNa2b 350 4.19E-0? 1.55E+05 DOM 7h-ll IFNa2b 670 Τ〇2Ε<)ϊ- 7.00E+05 DOM 7h-ll-12 — IFNa2b 500 T66E^〇l— 3.90E+05 | DOM 7h-ll-15 IFNa2b 10 1.87E^〇3~ 1 ~~— 3.50E+05 當將IFN(x2b與AlbudAb變體連接時，在所有情況下，
AlbudAb與血清白蛋白結合之親和力均降低。DOMTh-M-iO及 DOM7-11-15與親 本相比在所有 物種中 均保留 改良之 對血清白蛋白之結合親和力。DOM7h-11 -12與親本相比亦 在所有物種中均展示改良之對血清白蛋白之結合親和力。 表13 :生物物理表徵 藉由如上所述之SEC MALLS及DSC對單一 AlbudAb進行 生物物理表徵。
AlbudAb 融合物 DMS編號 生物物理參數 SEC MALLS DSC Tm(°C) DOM 7h-14 IFNa2b DMS7321 M/D 58-65 DOM 7h-14-10 IFNa2b DMS7322 M/D 55-65 DOM 7h-14-18 IFNa2b DMS7323 M/D 55-65 DOM 7h-14-19 IFNa2b DMS7324 M/D 59-66 DOM 7h-ll IFNa2b DMS7325 M/D 65.8-66.2 DOM 7h-ll-12 IFNa2b DMS7326 M/D 67-67.3 DOM 7h-ll-15 IFNa2b DMS7327 M/D 56.3-66.2 146451.doc -111 - 201042039 體且在10分鐘；1小時；8小時；24小時；48小時；72小 時；96小時取血清樣品。藉由EASY ELISA，根據製造商 說明書（GE Healthcare，目錄號RPN5960)來分析血清含 量。 表14 : 〇 物種 AlbudAb 融合物 白蛋白 KD(nM) PK參數 AUC hxpg/ml CL ml/h/kg tl/2 h Vz ml/kg 大鼠 7h-14 IFNa2b 350 832.1 2.4 27 94.5 7h-14-10 IFNa2b 16 1380.7 1.5 35.8 75.2 7h-14-18 IFNa2b 780 691.2 2.9 22.4 93.7 7h-14-19 IFNa2b 1900 969.4 2.2 25 78.7 7h-ll IFNa2b 6000 327.9 6.5 11 101.9 7h-ll-12 IFNa2b 1700 747.1 2.8 25.8 104.7 7h-ll-15 IFNa2b 200 1118.7 1.8 39.5 103.6 小鼠 7h-14 IFNa2b 240 761.2 2.6 30.4 115.3 7h-14-10 IFNa2b 60 750.5 2.7 30.9 118.6 7h-ll IFNa2b 6000 493.9 4.0 8.8 51.2 7h-ll_12 IFNa2b 150 439.6 4.5 21.5 140.9 7h-ll-15 IFNa2b 28 971.8 2.1 33.6 99.6 使用非隔室模型來擬合自大鼠及小鼠研究獲得之藥物動 力學參數。關鍵詞：AUC :自給藥時間外推至無限獲得之 曲線下面積；CL:清除率；tl/2:為血液濃度變為一半之 時間；Vz :基於終末階段之分布的體積。 146451.doc •113- 201042039 在大鼠及小鼠中測試IFNa2b-AlbudAb。在大鼠與小鼠 中，對於所有IFNa2b-DOM7h-ll變體融合蛋白，tl/2與親 本相比均獲改良。tl/2改良與對血清白蛋白之活體外KD改 良有關。對於IFNa2b-DOM7h-14-10變體，對血清白蛋白 之活體外KD改良亦與大鼠中tl/2之改良有關。 所有IFNa2b-AlbudAb融合蛋白均顯示與單一 AlbudAb相 比對RS A之結合降低5至10倍。此作用對於DOM7h-14系列 比DOM7h-ll系列（僅降低5倍）更顯著（亦即10倍）。 實例8 ··與蛋白質、肽及NCE之其他AlbudAb融合物。 €) 測試各種與其他化學實體（亦即域抗體（dAb)、肽及NCE) 融合之AlbudAb。結果展示於表15中。 表15 : 物種 AlbudAb 融合物 白蛋白 KD(nM) PK參數 AUC hxpg/ml CL ml/h/kg tl/2 h Vz ml/kg 大鼠 DOM7h-14 腸促胰島素類似物-4 2400 18 57.1 11 901.9 DOM7h-14-10 腸促胰島素類似物-4 19 43.6 23.1 22.1 740.3 DOM7h-14-18 腸促胰島素類似物-4 16000 16.9 75.7 9.4 1002.5 DOM7h-14-19 腸促胰島素類似物-4 17000 31.4 32.5 11.9 556.7 1 DOM7h-ll 腸促胰島素類似物-4 24000 6.1 168 7.1 1684.1 DOM7h-ll-12 腸促胰島素類似物-4 1400 24.2 59.9 13 1068.7 DOM7h-ll-15 腸促胰島素類似物-4 130 36.3 27.6 19.3 765.7 DOM7hl4-10 NCE-GGGGSC 62 DOM7hl4-10 NCE-TVAAPSC 35 人類 DOM7h-14 NCE 204 小鼠 DOM7h-ll DOMlm-21-23 234 10.7 4.7 72.5 DOM7h-ll-12 DOMlm-21-23 755 3.3 18 86.2 DOM7h-ll-15 DOMlm-21-23 1008 2.5 17.4 62.4 關鍵詞：DOMlm-21-23為抗TNFR1 dAb，腸促胰島素類 146451.doc •114- 201042039 似物-4為長39個胺基酸之肽（GLP-1促效劑）。下文描述 NCE、NCE-GGGGSC及NCE-TVAAPSC。 吾人先前已描述了使用與結合白蛋白之dAb(AlbudAb)之 遺傳融合物來延長抗TNFR1 dAb之活體内PK半衰期（例如 參看 WO 04003019、WO 2006038027、WO 2008149148)。 參考此等PCT申請案中之方案。在上表中，DOMlm-21-23 為抗小鼠TNFR1 dAb。 為製造結合血清白蛋白的腸促胰島素類似物-4之遺傳融 合物或與DOM7h-14(或其他AlbudAb)之遺傳融合物，將腸 促胰島素類似物-4-連接子-AlbudAb序列選殖至pTT-5載體 (可獲自CNRC，Canada)中。在各情況下，腸促胰島素類似 物-4位於構築體之5'端且dAb位於3'端。連接子為（G4S)3連 接子。使用鹼溶解（使用無内毒素質體Giga套組，其可獲 自Qiagen CA)在大腸桿菌中製備無内毒素DNA且用以轉染 HEK293E細胞（可獲自CNRC, Canada)。每燒瓶使用333 μΐ 293fectin(invotrogen)及 250 pg DNA轉染至每燒瓶 250 毫升 密度為1.75 X 106個細胞/毫升之HEK293E細胞中，且在30°C 下表現5天。藉由離心收集上清液且藉由蛋白質L上之親和 力純化進行純化。使蛋白質與樹脂分批結合，填充於管柱 上且以10管柱體積之PBS洗滌。以50 ml 0.1 Μ甘胺酸（pH 2)溶離蛋白質且以Tris(pH 8)中和。在SDS-PAGE膠凝上 鑑別具有預期大小之蛋白質。 NCE Albudab融合物：
測試新穎化學實體（NCE)AlbudAb融合物。合成具有PEG 146451.doc -115- 201042039 連接子（PEG 4連接子（亦即在順丁烯二醯亞胺之前具有4個 PEG分子））及順丁烯二醯亞胺基團之NCE(—種小分子 ADAMTS-4抑制劑）以便與AlbudAb接合。經由胺基酸位置 R108C處工程改造之胱胺酸殘基將NCE接合於AlbudAb或 將NCE接合於AlbudAb中AlbudAb末端工程改造之5個胺基 酸（GGGGSC)或6個胺基酸（TVAAPSC)間隔基之後。簡言 之，用TCEP(Pierce，目錄號77720)還原AlbudAb，使用 PD10 管柱（GE healthcare)脫鹽至 25 mM Bis-Tris、5 mM £〇丁八、10%(乂~)甘油（？116.5)中。將5倍莫耳過量之經順 丁烯二醢亞胺活化之NCE添加於DMSO中不超過10%(V/V) 最終濃度。在室溫下培育反應隔夜且廣泛透析至20 mM Tris(pH 7.4)中。 PEG連接子：
序列： DOM7h-14 R108C ： DIQMTQSPSSLSASVGDRVTITCRASQWIGSQLSWYQQKPGKAPKLLIMWRSSL QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQGLRHPKTFGQGTKVEIKC (SEQ IDNO:412) 146451.doc •116· 201042039 核苷酸： GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACC GTGTCACCATCACTTGCCGGGCAAGTCAGTGGATTGGGTCTCAGTTATCTTG GTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCATGTGGCGTTC CTCGTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGAC AGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCTACGTAC TACTGTGCTCAGGGTTTGAGGCATCCTAAGACGTTCGGCCAAGGGACCAAG GTGGAAATCAAATGC (SEQ ID NO:413)
關於 DOM7h-14-10/TVAAPSC 及 DOM7h-14-10/GGGGSC (亦即DOM7h-14-10/G4SC)之序列，請參看表5。 NCE-AlbudAb DOM7h-14-10 GGGGSC 及 DOM7hl4-10 O TVAAPSC當與化學實體融合時如藉由BIAcore所測定顯示 對RSA之活體外親和力（KD)降低5至10倍。然而未獲得此等 分子之PK資料。 dAb-Albudab融合物：對RSA具有最高親和力之2種 DOM7h-ll AlbudAb 當與治療域抗體（DOMlm-21-23)融合 時，如藉由BIAcore所測定，與未融合AlbudAb相比，對 RSA之親和力降低2倍。DOM7h-ll純系展示微莫耳濃度 Κ〇，其中融合時為2.8 μΜ且未融合時為約5 μΜ。 〇 腸促胰島素類似物4-AlbudAb融合物：AlbudAb與肽融合 對結合RSA之能力的影響為約10倍，例外為DOM7h-14-10，其僅展示結合降低4倍。然而，對於DOM7h-14系列 (除DOM7h-14-10之外），該影響與對於DOM7h-ll系列所見 相比更顯著。 對於所有以上資料，融合物之T1/2均隨對物種SA之親和 力改良而增加。 當AlbudAb-藥物融合物展示0.1 nM至10 mM之血·清白蛋 146451.doc -117- 201042039 白結合親和力範圍（KD)時，吾人一般將AlbudAb-治療劑歸 類為治療上適用（以用於治療及/或預防疾病、病狀或適應 症）。 吾人如下定義AlbudAb及AlbudAb融合物（蛋白質-AlbudAb，例如IFNa2b-DOM7h-14-10 ;肽-AlbudAb，例如 腸促胰島素類似物-4-DOM7h-14-10 ; dAb-AlbudAb，例如 DOMlm21-23-DOM7hll-15 ; NCE-AlbudAb，例如 ADAMTS-4-DOM7h-14-10)之治療範圍：展示適用於慢性或急性病 狀、疾病或適應症之療法的親和力（KD)範圍。亦展示標記 為「中度」之親和力範圍。此範圍中之AlbudAb及融合物 適用於慢性或急性疾病、病狀或適應症。以此方式， AlbudAb或融合物對血清白蛋白之親和力可根據待解決之 疾病、病狀或適應症來調整或選擇。如上所述，本發明提 供具有允許將各AlbudAb分類為「高親和力」、「中等親和 力」或「低親和力」，由此使熟習此項技術者能夠根據手 邊療法選擇本發明之適當AlbudAb之親和力的AlbudAb。 參看圖2。 實例 9 : DOM7h-ll-15sl2P序列 DOM7h-ll-15sl2P之胺基酸序列 DIQMTQSPSSLPASVGDRVTITCRASRPIGTMLSWYQQKPGKAPKLLILAFSRLQ SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQAGTHPTTFGQGTKVEIKR (SEQ ID NO: 414) 本發明之一態樣提供包含DOM7h-ll-15sl2P之核苷酸序 列或與該所選序列至少80% —致之核苷酸序列的核酸。使 用以下核酸序列（加下劃線之C表示在位置12產生脯胺酸之 146451.doc •118- 201042039 變化（相對於編碼DOM7h-ll-15之核酸））製備DOM7h-ll-15S12P ：
GACATCCAGATGACCCAGTCTCCATCCTCCCTGCCTGCATCTGTAGGAGACC
GTGTCACCATCACTTGCCGGGCAAGTCGTCCGATTGGGACGATGTTAAGTTG
GTACCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCCTTGCTTTTTCC
CGTTTGCAAAGTGGGGTCCCATCACGTTTCAGTGGCAGTGGATCTGGGACA
GATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCTACGTACT
ACTGCGCGCAGGCTGGGACGCATCCTACGACGTTCGGCCAAGGGACCAAGG TGGAAATCAAACGG (SEQ ID NO: 415) 在PCR中藉由使用DOM7h-ll-15作為模板來構築DOM7h- 11-15S12P，其中使用引子來引入S12P突變。引子序列為：
〇 GCAACAGCGTCGACGGACATCCAGATGACCCAGTCTCCATCCTCCCTGCCTG CATCTGTAGG (SEQ ID NO: 416) ° 本發明之一替代性態樣提供包含SEQ ID NO: 415之核苷 酸序列或與該所選序列至少80% —致之核苷酸序列的核 酸。在一個實施例中，DOM7h-ll-15S121^、由以下載體編 碼且自以下載體表現：該載體含有連接區域及編碼蛋白質 或肽藥物或單一可變域或其他抗體片段之C端序列以產生 串聯蛋白質融合產物。在一個實施例中，連接子包含胺基 Q 酸序列TVA，例如TVAAPS。本發明之其他態樣為包含該 核酸之載體；及包含該載體的經分離之宿主細胞。本發明 亦提供治療或預防患者之疾病或病症之方法，其包含投與 該患者至少一劑DOM7h-ll-15sl2P。 【圖式簡單說明】 圖1A及IB : DOM7h-ll變體dAb之胺基酸序列比對。特 定位置之「.」指示與在DOM7h-ll中該位置所見相同之胺 基。CDR由加下劃線及粗體文本指示（第一加下劃線序列 為CDR1，第二加下劃線序列為CDR2且第三加下劃線序列 146451.doc -119- 201042039 為CDR3);及 圖2A至2D : DOM7h-11變體之動力學參數。KD單位 =nM ; Kd 單位 sec·1 ; Ka 單位。符號 A e-B 意謂 八><1〇-8且〇 e D意謂CxlOD。指示如下文實例支持之各種物 種中之總體動力學範圍。亦提供可選範圍以供在特定治療 環境中使用（急性或慢性適應症、病狀或疾病及用於慢性 與急性環境之「中度」）。高親和力dAb及包含此等dAb之 產物適用於慢性環境。中等親和力dAb及包含此等dAb之 產物適用於中度環境。低親和力dAb及包含此等dAb之產 ◎ 物適用於急性環境。親和力就此而言為對血清白蛋白之親 彳力列出各種實例抗血清dAb及融合蛋白，且此等^八^ 支持所揭示之範圍。許多實例在人類及一或多種非人類動 物中（例如在人類及獼猴及/或小鼠中）具有有利動力學。 d A b或包含其之產物的選擇可根據本發明視待以治療 處理之環境（例如慢性或急性）來調整。 、工
146451.d. -120- 201042039 序列表 <110>英商葛蘭素集團有限公司 <120>改良之抗血清白蛋白結合變體
<130> DB63556 WO <140> TW 099105020 <141> 2010-02-22 <150> 61/153,746 <151> 2009-02-19 <150> 61/163,987 <151> 2009-03-27 〇<150> 61/247,136 <151〉 2009-09-30 <160> 420 <170> FastSEQ for Windows Version 4.0 <210〉 1 <211> 108 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 1
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Leu Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 100 105 <210> 2 <211〉 108 <212> PRT <213>人工序列 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 2
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr He Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Leu Ala Phe Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 100 105 <210> 3 <211> 108 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 3
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Trp Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr His Cys Ala Gin Ala Gly Thr His Pro Thr 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 100 105 <210> 4 <211> 108 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 4
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Leu Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly -2- 146451-序列表.doc 201042039 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Thr Gly Thr His Pro Thr 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 100 105 <210> 5 <211> 108 <212> PRT <213>人工序列 <2'20> <223>來源於人類生殖系序列 <400> 5
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15
Asp Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Thr 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Leu Trp Asn Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu He Lys Arg 100 105 <210> 6 <211> 324 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 6 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtcg tccgattggg acgatgttaa gttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatcttgttt ggttcccggt tgcaaagtgg g&tcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgtgcgcag gctgggacgc atcctacgac gttcggccaa 300 gggaccaagg tggaaatcaa acgg 324 <210> 7 <211> 324 <212> DNA <213>人工序列 <220〉 <2+23>來源於人類生殖系序列 <400> 7 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtcg tccgattggg acgatgttaa gttggtacca gcagaaacca 120 146451-序列表.doc 201042039 gggaaagccc ctaagctcct gatccttgct ttttcccgtt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgcgcgcag gctgggacgc atcctacgac gttcggccaa 300 gggaccaagg tggaaatcaa acgg 324 <210> 8 <211> 324 < 212> IM <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 8 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtcg tccgattggg acgatgttaa gttggtacca gcagaaacca 120 gggaaagccc caaagctcct gatctggttt ggttcccggt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacca ctgtgcgcag gcggggacgc atcctacgac gttcggccaa 300 gggaccaagg tggaaatcaa acgg 324 <210> 9 <211> 324 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 9 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtcg tccgattggg acgatgttaa gttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatcttgttt ggttcccggt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacggat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgtgcgcag actgggacgc atcccacgac gttcggccaa 300 gggaccaagg tggaaatcaa acgg 324 <210> 10 <211> 324 <212> DNA <213>人工序列 <22Q> <223>來源於人類生殖系序列 <400> 10 gacatccaga tgacccaglc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtcg tccgattggg acgacgttaa gttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatcctttgg aattcccgtt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgtgcgcag gctgggacgc atcctacgac gttcggccaa 300 gggaccaagg tggaaatcaa acgg 324 <210> 11 <211> 120 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 146451-序列表.doc 201042039 <400> 11
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gin Tyr 20 25 30
Arg Met His Trp Val Arg Gin Ala Pro Gly Lys Ser Leu Glu Trp Val 35 40 45
Ser Ser lie Asp Thr Arg Gly Ser Ser Thr Tyr Tyr Ala Asp Pro Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Ala Val Thr Met Phe Ser Pro Phe Phe Asp Tyr Trp Gly Gin 100 105 110
Gly Thr Leu Val Thr Val Ser Ser 115 120
<210> 12 <211> 123 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 12
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala A3 a Ser Gly Phe Thr Phe Ala Asp Tyr 20 25 30
Gly Met Arg Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Ser lie Thr Arg Thr Gly Arg Val Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Trp Arg Asn Arg His Gly Glu Tyr Leu Ala Asp Phe Asp Tyr 100 105 110
Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser 115 120 <210〉 13 <211> 120 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 13
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Met Arg Tyr 20 25 30
Arg Met His Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 146451-序列表.doc 201042039
Ser Ser lie Asp Ser Asn Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Asp Arg Thr Glu Arg Ser Pro Val Phe Asp Tyr Trp Gly Gin 100 105 110
Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 14 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 14
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Asp Tyr 20 25 30
Glu Met His Trp Val Arg G3n Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Ser lie Ser Glu Ser Gly Thr Thr Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Arg Arg Phe Ser Ala Ser Thr Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 15 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 15
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15 .Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Thr Gly His Trp Glu Pro Phe Asp Tyr Trp Gly Gin G]y 146451·序列表.doc 201042039 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 16 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 16
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 — Ser Gin He Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 〇 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Thr Gly Arg Trp Glu Pro Tyr Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 17 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 17
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Tlir Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 18 <211> 119 146451-序列表.doc 201042039 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 18
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 19 <211> 119 <212> PRT <213>人工序列 <220> <_223>來源於人類生殖系序列 <400> 19
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 20 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 20 146451·序列表.doc 201042039
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Met Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 21 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 21
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Asp Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 22 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 22
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val -9- 146451-序列表.doc 201042039 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Thr Gly Arg Trp Glu Pro Phe Asp His Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 23 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 23
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 24 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 24
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110 -10- 146451-序列表.doc 201042039
Thr Leu Val Thr Val Ser Ser 115 <210> 25 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 25
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr '20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 26 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 26
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala A]a Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 27 <211> 119 <212> PRT -11 - 146451-序列表.doc 201042039 <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 27
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Lea Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 28 <211> U9 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 28
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp G]y Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 29 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 29
Glu Val Gin Leu Leu Glu Ser G]y Gly Gly Leu Val Gin Pro Gly Gly -12· 146451-序列表.doc 201042039 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Asp Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asrt Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys G]y Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 30 <211> 119 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 30
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Lea Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Asp Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu G]n Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 〇 115 <2I0> 31 <211> 119 <212〉 PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 31
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60 •13· 146451·序列表.doc 201042039
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 A3a He Tyr Thr Gly Arg Trp Glu Pro Phe Va] Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 32 <211> 119 <212> PRT <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 32
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr A]a Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 33 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 33
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Lys Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser -14- 14645卜序列表.doc 201042039 115 <210> 34 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 34
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 35 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 35
Glu Val Gin Leu Leu Glu Ser G)y Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly G3n Gly 100 105 110
Thr Lea Val Thr Val Ser Ser 115 <210> 36 <211> 119 <212> PRT <213>人工序列 15- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 36
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser G]n lie Ala Asn Thr G】y Asp Arg Arg Tyr Tyr A]a Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ala Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin GJy 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 37 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 37
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala A]a Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asn Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 38 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 38
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15 -16· 146451-序列表,doc 201042039
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Va] Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr A]a Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 39 <211> 119 <212> PRT <213>人工序列 〇 <220> <223>來源於人類生殖系序列 <400> 39
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Ser Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg A]a Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Asp Asn Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 〇
<210> 40 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 40
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe lie Thr Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr -17- 146451-序列表.doc 201042039 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Gin Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Vai Ser Ser 115
<210> 41 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 41
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asn Thr Gly Asp Arg Thr Tyr Tyr A]a Asp Ser Val 50 55 60
Lys Gly Arg Phe Tlir lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 42 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 42
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 35
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Va3 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 AJa He Tyr Thr Gly Arg Trp G]u Pro Phe Asp Tyr Trp G]y Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 18- 146451-序列表.doc 201042039 <210> 43 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 43
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 44 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 44
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 45 <211> 119 <212> PRT <213>人工序列 19- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 45
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Lys Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 46 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 46
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Glu Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Pro Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Va] Ser Ser 115 <210> 47 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 47
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Asn Tyr •20- 146451-序列表.doc 201042039 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Tyr Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Thr Ser 115
<210> 48 <211> 119 <212> PRT <213>人工序列
<220> <223〉來源於人類生殖系序列 <400> 48
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 49 <211> 119 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 49
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 -21 - 146451-序列表.doc 201042039
Leu Gin Met Asn Ser Leu Arg Ala GIu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Lys Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 50 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 50
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr I3e Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 51 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 51
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly i 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala I)e Tyr Thr G]y Arg Trp Arg Pro Phe G]u Tyr Trp Gly Gin G3y 100 105 110
Thr Leu Val Thr Val Ser Ser 115 22- 146451-序列表.doc 201042039 <210> 52 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 52
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Va] Tyr Tyr Cys
S5 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 53 <211> 119 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 53
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Val Tyr Thr Gly Arg Trp G3u Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 54 <211> 119 <212> PRT <213>人工序列 <220> -23- 146451-序列表.doc 201042039 <223>來源於人類生殖系序列 <400> 54
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys A]a A]a Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu GJn Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Lys Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 120
Thr Leu Val Thr Val Ser Ser 115 <210> 55 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 55
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala A]a Ser Gly Phe Thr Phe Va] Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg G3n Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Pile Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly Ϊ00 105 no
Thr Leu Val Thr Val Ser Ser 115 <210> 56 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 56
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30 -24· 14645卜序列表.doc 201042039
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 57 <211> 119 <212> PRT <2i3>人工序列 <220>
<223>來源於人類生殖系序列 <400> 57
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 58 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 58
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys -25- 146451-序列表.doc 201042039 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210〉 59 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 59
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Lys Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 60 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 60
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 -26- 146451-序列表.doc 201042039 <210> 61 <211〉 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 61
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly PKe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Rie Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu G)n Met Asn Ser Leu Arg A]a Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala lie Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210〉 62 <211> 119 <212〉 PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 62
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 '25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 63 <211> 119 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 -27- 146451-序列表.doc 201042039 <400> 63
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 A]a I)e Tyr Thr Gly Arg Trp GJu Pro Plie Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 64 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 64
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Plie Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Lys Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 65 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 65
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val G)n Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val -28- 146451-序列表.doc 201042039 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 66 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Str Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 67 <211> 119 <212> PRT <213〉人工序列 <220〉 <223>來源於人類生殖系序列 <400> 67
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 •29- 146451-序列表.doc 201042039
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 68 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 68
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Phe 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 69 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 69
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 70 146451-序列表.doc -30- 201042039 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 70
Glu Val Gin Leu Leu GIu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg G3n Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 71 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 71
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr G]y Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 72 <211〉 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 -31 - 146451-序列表.doc 201042039 <400> 72
Glu Val Gin Leu Leu Glu Ser G]y Gly G】y Leu Va】G]n Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ala Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Pro Asp Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 73 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 73
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ala Tyr Tyr Cys 85 90 95
Ala lie Tyr Tlir Gly Arg Trp Pro Asp Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 74 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 74
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val G3n Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 32- 146451-序列表.doc 201042039
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Pro Asp Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 75 <211> 119 <212> PRT <213>人工序列 <220>
<223>來源於人類生殖系序列 <400> 75
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Pro Asp Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Va丨 Ser Ser 115 <210> 76 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 76
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Pro Asp Phe Asp Tyr Trp Gly Gin Gly -33- 146451·序列表.doc 201042039 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 77 <211> 119 <212〉 PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 77
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Pro Asp Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 78 <211> 139 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 78
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Ala Trp Gly Asp Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 79 <211> 119 -34- 146451-序列表.doc 201042039 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 79
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Gly Gly Gin Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 80 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 80
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin He Ser Asp Ser Gly Tyr Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu G)n Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 81 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 81 35- 146451-序列表.doc 201042039
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Gly Gly Thr Arg Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 82 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 82
Glu Val Gin Leu Leu Glu Ser Giy Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala A]a Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg G]n Ala Pro Gly Lys G】y Pro Glu Trp Val 35 40 45
Ser Gin lie »Ser Asp Lys G]y Thr Arg Thr Tyr Tyr Ala Asp Ser Va] 50 55 60
Lys G)y Arg Phe Thr I]e Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu GJn Met Asn Ser Leu Arg A]a Glu Asp Thr A]a Va] Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> S3 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 83
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg G3n Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin lie Ser Glu Thr Gly Arg Arg Thr Tyr Tyr Ala Asp Ser Val -36- 146451·序列表.doc 201042039 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Asp Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 84 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 84 —_ Glu Val Ghi Leu Leu Glu Ser O 1 5 Ser Leu Arg Leu Ser Cys Ala 20 Ser Met Gly Trp Val Arg Gin 35 Ser Gin lie Asn Asn Thr Gly 50 55 Lys Gly Arg Phe Thr He Ser 65 70 Leu Gin Met Asn Ser Leu Arg 85 Ala lie Tyr Thr Gly Arg Trp 100 Thr Leu Val Thr Val Ser Ser 115
Gly Gly Gly Leu Val Gin Pro Gly Gly 10 15 Ala Ser Gly Phe Thr Phe Val Lys Tyr 25 30 Ala Pro Gly Lys Gly Leu Glu Trp Va] 40 45 Ser Thr Thr Tyr Tyr Ala Asp Ser Val 60 Arg Asp Asn Ser Lys Asn Thr Leu Tyr 75 80 Ala Glu Asp Thr Ala Val Tyr Tyr Cys 90 95 Glu Pro Phe Asp Tyr Trp Gly Gin Gly 105 110
<210> 85 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 85
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Pbe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro Glu Trp Val 35 40 45
Ser Gin He Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110 -37- 146451-序列表.doc 201042039
Thr Leu Val Thr Val Ser Ser 115 <210> 86 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 86
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Pro G]u Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <2I0> 87 <211> 119 <212> PRT <213〉人工序列 <220> <223〉來源於人類生殖系序列 <400> 87
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys S5 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 88 <211> 119 <212> PRT •38· 146451-序列表.doc 201042039 <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 88
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala A]a Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110 表 Thr Leu Val Thr Val Ser Ser o ⑴
<210> 89 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 89
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 90 <211〉 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 90
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly -39- U6451-序列表.doc 201042039 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Thr His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 91 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 91
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr A]a Asp Arg Arg Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210〉 92 <211> 119 <212〉 PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 92
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Leu Asn Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60 •40· 14645〗-序列表.doc 201042039
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Tlir Leu Val Thr Val Ser Ser 115 <210> 93 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 93
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 94 <211> 119 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 94
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Arg Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser -41 - 146451_序列表.doc 201042039 115 <210> 95 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 95
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Va] 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Arg Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 96 <2il> 119 <212> PRT <213〉人工序列 <220〉 <223>來源於人類生殖系序列 <400〉 96
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Va] Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Val Tyr Thr Gly Arg Trp Val Ser Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 97 <211> 119 <212> PRT <213>人工序列 42- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 97
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Leu Tyr Thr Gly Arg Trp Val Ser Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 98 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 98
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asn Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Val Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 99 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 99
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val G]n Pro Gly Gly 15 10 15 •43- 146451-序列表.doc 201042039
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Va] Arg Gin A]a Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Tlir Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Leu Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 100 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 100
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser G]n lie Ala Asn Thr A]a Asp Arg Arg Tyr Tyr A]a His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu GJn Met Asn Ser Leu Arg Ala Glu Asp Thr A]a Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp G]y Gin Gly 100 105 110
Thr Leu Val Thr Va] Ser Ser 115 <210> 101 <211> 119 <212> PRT <213〉人工序列 <220〉 <223>來源於人類生殖系序列 <400> 101
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Ala Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr -44 - 146451-序列表.doc 201042039 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Are Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 102 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 102
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Asp Arg Arg Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 103 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 103
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Ala Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr G]y Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 45· 146451-序列表.doc 201042039 <210> 104 <211> 119 <212> PRT <213〉人工序列 <220> <223〉來源於人類生殖系序列 <400> 104
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie AJa Asn Thr Gly Asp Arg Arg Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 105 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 105
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asn Thr Ala Asp Arg Arg Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 106 <211> 119 <212> PRT <213>人工序列 14645 卜序列表.doc -46- 201042039 <220> <223>來源於人類生殖系序列 <400> 106
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Ala Asp Arg Arg Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 107 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 107
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Aig Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Val Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr A.la Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 108 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 108
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr • 47- 146451·序列表.doc 201042039 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asn Thr Gly Asp Arg Arg Tyr Tyr Ala Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210〉 109 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 109
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin A]a Pro Gly Lys Gly Leu G]u Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly G1b Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 110 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 110
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro G]y Lys Gly Leu Giu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Plie Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80 • 48· 146451-序列表.doc 201042039
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 111 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 111
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210〉 i12 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 112
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin A]a Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ser His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 49· 146451-序列表.doc 201042039 <210> 113 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 113
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Thr His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 114 <211> 119 <212〉 PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 114
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Thr Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr I]e Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 SO
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 115 <211> 119 <212> PRT <213>人工序列 <220〉 •50- 146451-序列表.doc 201042039 <223>來源於人類生殖系序列 <400> 115
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 SO
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 116 <211> 119 <212> PRT <213〉人工序列 <220〉 <223>來源於人類生殖系序列 <400> 116
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 117 <21I> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 117
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30 -51 - 146451-序列表.doc 201042039
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr I]e Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys S5 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 118 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 118
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Va] Arg Gin Ala Pro Giy Lys Gly Leu GJu Trp Va] 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 119 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 119
Glu Val G]n Leu Leu G]u Ser G]y Gly Gly Leu Val G)n Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg A]a Glu Asp Thr Ala Val Tyr Tyr Cys -52· 146451-序列表.doc 201042039 85 90 95 Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115
<210> 120 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 120
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ala Va] 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 121 <211> 119 <212〉 PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 121
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Ala Asp Arg Arg Tyr Tyr Asp Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 •53- 146451-序列表.doc 201042039 <210> 122 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 122
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser G]y Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Gly Asp Arg Arg Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 123 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 1.23
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Gly Asp Arg Arg Tyr Tyr Asp Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg AJa Gla Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Tlir Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> Γ24 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 -54- 146451-序列表.doc 201042039 <400> 124
Glu Va3 Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr G]y Arg Trp Gly Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 125 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 125
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Ala Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 126 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 126
Glu Va] Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val -55- 146451-序列表.doc 201042039 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Gly Pro Phe Gin Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 127 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 127
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Va] 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Glu Pro Phe G]n Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 128 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 128
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 -56- 146451-序列表.doc 201042039
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 129 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 129
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30 o
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Aia Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Gin Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 130 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 130
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Val Pro Phe Gin Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 131 57- 146451-序列表.doc 201042039 <21I> 119 <212> PRT <213〉人工序列 <220> <223〉來源於人類生殖系序列 <400> 131
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 132 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 132
Glu Val G]n Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 133 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 58- 146451-序列表.doc 201042039 <400> 133
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr A]a Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 134 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 134
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 135 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 135
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 -59- 146451-序列表.doc 201042039
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Pile Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Arg Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 no
Thr Leu Val Thr Val Ser Ser 115
<210> 136 <211> 119 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400〉 136
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg G3n Ala Pro Gly Lys Gly Leu Glu Trp Va] 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Plie Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Va] Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr GJy Arg Trp Glu Pro Phe Val Tyr Trp G]y Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 137 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 137
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu vSer Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly •60- 146451-序列表.doc 201042039 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 138 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 138
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 ❸
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ser His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 139 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 139
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ma Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ser His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 140 <211> 119 -61 - 146451-序列表.doc 201042039 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 140
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Thr His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 141 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 141
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Thr His Ser Va] 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210〉 142 <211> 119 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 142 62- 14645卜序列表.doc 201042039
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 143 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 143
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 144 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 144
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Leu Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp His Ser Val -63- 146451-序列表.doc 201042039 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala G]u Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 145 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 145
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser G]n lie Ala Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Plie Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 146 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 146
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110 -64- 146451-序列表.doc 201042039
Thr Leu Val Tlir Val Ser Ser 115 <210> 147 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 147
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr G]y Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 148 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 148
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val G]n Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu G3u Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Ala Asp Arg Thr Tyr Tyr Asp His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala I]e Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115
<210> 149 <211> 119 <212> PRT -65- 146451-序列表.doc 201042039 <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 149
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser G3n lie Ala Asp Thr Ala Asp Arg Arg Tyr Tyr Ala His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala I]e Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin G]y 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 150 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 150
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val G3n Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg G]n A]a Pro Gly Lys G]y Leu G]u Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Arg Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr I]e Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu G]n Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Va] Tyr Tyr Cys 85 90 95
Ala He Tyr Thr GJy Arg Trp Ala Pro Phe Glu Tyr Trp G]y G]n Gly 100 105 110
Thr Leu Va] Thr Va】 Ser Ser 115 <210> 151 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 151
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 146451-序列表.doc 201042039 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Va] Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ala Asp Thr Ala Asp Arg Arg Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Tlir Val Ser Ser 115
<210> 152 <211> 119 <212> PRT
<213>人工序列 <220> <223>來源於人類生殖系序列 <400> 152
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Arg Tyr Tyr Asp His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala He Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 〇 115 <210> 153 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 153
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Ala Asp Arg Arg Tyr Tyr Asp His Ala Val 50 55 60 -67- 146451-序列表.doc 201042039
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu G]n Met Asn Ser Leu Arg Ala G3u Asp Thr A]a Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> J54 <211> 119 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 154
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ala Asp Thr Ala Asp Arg Arg Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 155 <211> 119 <212> PRT <213〉人工序列 <220> <223〉來源於人類生殖系序列 <400〉 155
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Ala Asp Arg Arg Tyr Tyr Asp Asp Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Thr Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Glu Pro Phe Val Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser -68- 146451·序列表.doc 201042039 115 <210> 156 <211> 119 <212〉 PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 156 GIu Val Gin Leu Leu Glu Ser G]y Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin He Ser Asp Thr Ala Asp Arg Thr Tyr Tyr Ala His Ala Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr ϋ 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Val Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 157 <211> 119 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 157
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Val Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu G3u Trp Val 35 40 45
Ser Gin lie Ser Asn Thr Gly Gly His Thr Tyr Tyr Ala Asp Ser Val 50 55 60
Lys Gly Arg Phe Thr He Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys Tyr Thr Gly Arg Trp Glu Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 158 <211> 119 <212〉 PRT <213>人工序列 69- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <>158
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Phe Lys Tyr 20 25 30
Ser Met Gly Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Gin lie Ser Asp Thr Gly Asp Arg Arg Tyr Tyr Asp His Ser Val 50 55 60
Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala lie Tyr Thr Gly Arg Trp Ala Pro Phe Glu Tyr Trp Gly Gin Gly 100 105 110
Thr Leu Val Thr Val Ser Ser 115 <210> 159 <211> 360 <212> DNA <213〉人工序列 <220> <223>來源、於人類生殖系序列 <400> 159 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttatg aggtatagga tgcattgggt ccgccaggct ccagggaagg gtctagagig ggtctcatcg attgattcta atggttctag tacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaagatcgt acggagcgtt cgccggtttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc <210> 160 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 160 gaggtgcagc tgttggagtc tgggggaggc ttggtgcagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt gattatgaga tgcattgggt ccgccaggct ccagggaagg gtctagagtg ggtctcatct attagtgaga gtggtacgac gacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaacgtcgt ttttctgctt ciacgtttga ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 161 <211> 357 <212> CNA <213>人工序列 70- 146451·序列表.d〇c 201042039 <220> <223>來源於人類生殖系序列 <400> 161 gaggtgcagc tgitggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcattggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 162 <211> 357 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 162 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcgttggg agccttatga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 163 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 163 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 164 <211> 357 <212> IM <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 164 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcgttggg agccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 165 <211> 357 -71 - 146451-序列表.doc 201042039
<212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 165 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 166 <211> 357 <212> \m <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 166 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 167 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 167 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tgggatgggt ccgccaggct 120 ccagggaaag gtccagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcacagt ctcgagc 357 <210> 168 <211> 357 <212> 脆 <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 168 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccata tcccgcgaca attccaagaa cacgctgtat 240 atgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 -72- 146451·序列表.doc 201042039 <210> 169 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 169 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttggt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg atctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 170 <211> 357 <212> DNA <2i3>人工序列 Ο <220> <223>來源於人類生殖系序列 <400> 170 gaggtgcagc tgttggagtc agggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtggtca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcgttggg agccttttga ccactggggt caggggaccc tggtcaccgt ctcgagc 357 <210> 171 <211〉 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 171
gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca aticcaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 172 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 172 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180 -73- 146451-序列表.doc 201042039 gcagactccg tgaagggccg gttcaccaic tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 173 <211> 357 <212> DNA <213>人工序列 <220> <223>來涿於人類生殖系序列 <400> 173 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg sgtctcacag atttcgaata cgggtgatcg tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 174 <211> 357 <212> DNA <213>人工序列 <220> <2_23>來源於人類生殖系序列 <400> 174 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cclccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata csggtgatca tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 175 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 175 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tgggatgggt ccgccaggct 120 ccagggaaag gtccagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcacagt ctcgagc 357
<210> 176 <211〉 357 <212> DNA <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 176 74- 146451-序列表.doc 201042039 gaggtgcagc tcctgtgcag ccagggaaag gcagactccg ctgcaaatga ggtcgttggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tgggatgggt ccgccaggct 120 gtccagagtg ggtctcacag atttcgaata cgggtgatca tacatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 agccttttga ctactggggt cagggaaccc tggtcacagt ctcgagc 357 <210> 177 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 177 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttggt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg atctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 178 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 178 gaggtgcagc tcctgtgcag ccagggaagg gcagactccg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt atctagagtg tgaagggccg acagcctgcg agccttttga tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cacctttggt aagtattcga tggggtgggt ccgccaggct 120 ggtctcacag atttcgaata cgggtgatca tacatactac 180 gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 tgccgaggac accgcggtat attactgtgc gatatatacg 300 ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 179 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 179 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 180 <211〉 357 <212> Wk <213>人工序列 <220> 146451-序列表.doc 75- 201042039 <223>來源於人類生殖系序列 <400> 180 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctitgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 181 <211> 357 <212> im <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 181 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac gcggactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatacg ggtcgttgga agccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 182 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 182 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac gcagactccg t£aagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 183 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 183 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacaiactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc
<210> 184 <211> 357 <212〉IM 76· 146451-序列表.doc 201042039 <213>人工序列 <220> <223>來源、於人類生殖系序列 <400> 184 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggcat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 185 <211> 357 <212> DNA <2i3>人工序列 <220> <223>來源於人類生殖系序列
<400> 185 gaggtgcagc tcctgtgcag ccagggaagg gcacactccg ctgcaaatga ggtcgttggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 agccttttaa ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 186 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 186 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180
gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 187 <211> 357 <212> DNA' <213>人工序列 <220> <223〉來涿於人類生殖系序列 <400> 187 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa ctcgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg tgccttttga caactggggt cagggaaccc tggtcaccgt ctcgagc 357 77- 146451-序列表.doc 201042039 <210> 188 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 188 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttatt acgtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttca gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 189 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 189 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttggt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac gcggactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 190 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 190 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttttt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaagac accgcggtat attactgtgc gataiatacg ggtcgttggg agccltttga ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 191 <211> 357 <212> DNA <2i3>人工序列 <220> <2_23>來猓於人類生殖系序列 <400> 191 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat -78- 146451-序列表.doc 201042039 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 192 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 192 gaggtgcagc tcctgtgcag ccagggaagg gcagacgcgg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt gtctagagtg tgaaggggcg acagcctgcg agccttttga tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac ctactggggt ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcgaata cgggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357
<210> 193 <211> 357 <212> DNA <213>人工序列
<220> <223>來源於人類生殖系序列 <400> 193 gaggtgcagc tgttggagtc tgggggaggc tcctgtgcag cctccggatt cacctttgtt ccagggaagg gtctagagtg ggtctcacag gcagactccg tgaagggccg gttcaccatc ctgcaaatga acagcctgcg tgctgaggac ggtcgttggg agccttttaa gtactggggt <210> 194 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 194 gaggtgcagc tgttggagtc tgggggaggc tcctgtgcag cctccggatt cacctttagt ccagggaagg gtctagagtg ggtctcacag gcagactcag tgaagggccg gttcaccatc ctgcaaatga acagcctgcg tgccgaggac ggtcggtggg agccttttga atactggggt ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcgaata cgggtgatcg tacatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcgaata cgggtgagcg tagatactac 180 tcccgcgaca atcccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 <2I0> 195 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 195 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 -79- 14645〗·序列表.doc 201042039 tcctgtgcag cctccggatt cacctttgtt aactattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tacatactac 180 gcggactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttatga gtactggggt cagggaaccc tggtcaccgt cacgagc 357 <210> 196 <211> 357 <212〉 DMA <213>人工序列 <220> <2_23>來涿於人類生殖系序列 <400> 196 gaggtgcasc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgata attccaagaa cacactgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210〉 197 <211> 357 <212〉 DNA <213>人工序列 <220> <223〉來源於人顓生殖系序列 <400> 197 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga agccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 198 <211> 357 <212> m <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 198 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 199 <211> 357 <212> IM <213>人工序列 <220> <223>來源於人類生殖系序列 -80- 146451-序列表.doc 201042039 <400> 199 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 200 <211> 357 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 200 gaggtgcagc tcctgtgcag ccagggaagg gcagactctg ctgcaaatga ggtcggtggg
tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atigcgaata cgggtgatcg tagatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210〉 201 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 201 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggtatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 202 <211> 357 <212> Wk <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 202 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga agccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 203 <211> 357 <212> WA <213>人工序列 • 81" 146451-序列表 _doc 201042039 <220> <223>來源於人類生殖系序列 <400> 203 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 204 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <40〇> 204 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 205 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來泺於人類生殖系序列 <400> 205 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgiat 240 clgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <230> 206 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 206 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccgsatt cacctttgtt aagtattcga tggggtggst ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 207 82- 146451·序列表.doc 201042039 <211> 357 <2i2> IM <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 207 gaggtgcagc tcctgtgcag ccagggaagg gatgactctg ctgcaaatga ggtcgttgga tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg agccttttga tgggggaggc cacctttgtt ggtctcacag gt tcaccatc tgctgaggac gtactggggt ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggcc 120 atttcggata cgggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 <210> 208 <211> 357 <212> DNA <213>人工序列
<220> <223>來源於人類生殖系序列 <400> 208 ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcggata cgggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatact 300 cagggaaccc tggtcaccgt ctcgagc 357 gaggtgcagc tcctgtgcag ccagggaagg gatgactctg ctgcaaatga gggcgttggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg tgccttttga tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac gtactggggt <210> 209 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列
<400> 209 gaggtgcagc tgttggagtc tgggggaggc tcctgtgcag cctccggatt cacctttgtt ccagggaagg gtctagagtg ggtctcacag gatgactctg tgaagggccg gttcaccatc ctgcaaatga acagcctgcg tgccgaggac ggtcgttgga ggccttttga gtactggggt ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcggata cgggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 <210> 210 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcggata cgggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 <400> 210 gaggtgcagc tcctgtgcag ccagggaagg gatgactctg ctgcaaatga tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac •83· 146451-序列表.doc 201042039 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 211 <211> 357 <212> DNA <213〉人工序列 <220> <223〉來源於人類生殖系序列 <400> 211 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 212 <211> 357 <212> DNA <213〉人工序列 <220> <223>來源、於人類生殖系序列 <400> 212 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga agccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 213 <211> 357 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <>213 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga Tggggtgggt ccgccaggcc 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaagac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 214 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 214 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct i20 •84· 146451-序列表.doc 201042039 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 215 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 215 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 216 <211> 357 <212> mk <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 216 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttg aagttttcga tgggEtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 217 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 217 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttg aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 218 <211> 357 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 85- 146451-序列表.doc 201042039 <400> 218 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttg£g agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 219 <211> 357 <212> DNA <213>人工序列 <220> 來源於人類生殖系序列 <400〉 219 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttg aagtattcga tggggigggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 220 <211> 357 <212> DNA <213>人工序列 <220〉 <2_23>來源於人類生殖系序列 <400> 220 gaggigcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggcat attactgtgc gatatatacg 300 ggtcggtggc ccgactttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 221 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 221 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggcat attactgtgc gatatatacg 300 ggtcggtggc ccgactttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 222 <211> 357 <212> DNA <2〗3>人工序列 86- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 222 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggc ccgactttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 223 <211> 357 <212> DNA <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 223
gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggc ccgactttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 224 <211> 357 <212> DNA <213>人工序列 <220> <223>來源、於人類生殖系序列 <400> 224 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaaiga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggc ccgactttga ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 225 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 225 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggc ccgactttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 226 <211> 357 87- 146451-序列表.doc 201042039 <212> DNA <213>人工序列 <2'20> <223>來源於人類生殖系序列 <400> 226 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tgggatgggt ccgccaggct ccagggaaag gtccagagtg ggtctcacag atttcggcct ggggtgacag gacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 227 <211> 357 <212> DNA <213>人工序列 <220> <223>來源、於人類生殖系序列 <400〉 227 gaggtgcagc tgttggaglc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaaag gtccagagtg ggtctcacag atttcggacg gcggtcagag gacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 228 <211〉 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 228 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tgggatgggt ccgccaggct ccagggaaag gtccagagtg ggtctcacag atttcggact ccggttaccg cacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 229 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 229 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtccagagtg ggtctcacag atttcggacg ggggtacgcg gacatactac gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttga ctactggggt cagggaaccc tggtcaccgt ctcgagc -88- 146451-序列表.doc 201042039 <210> 230 <21I> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 230 gaggtgcagc tcctgtgcag ccagggaaag gcagactccg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt gtccagagtg tgaagggccg acagcctgcg agccttttga tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac ctactggggt ttggtacagc aagtattcga atttcggaca tcccgcgaca accgcggtat cagggaaccc ctggggggtc cctgcgtctc 60 tgggatgggt ccgccaggct 120 agggtacgcg cacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc 357 <210> 231 <211> 357 <212> Wk <213>人工序列 ❹ <220> <223>來源於人類生殖系序列 ctggggggtc cctgcgtctc 60 tgggatgggt ccgccaggct 120 ccggtcgcag gacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc . 357 <400> 231 gaggtgcagc tcctgtgcag ccagggaaag gcagactccg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt gtccagagtg tgaagggccg acagcctgcg agccttttga tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac ctactggggt ttggtacagc aagtattcga atttcggaga tcccgcgaca accgcggtat cagggaaccc <210> 232 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列
ctggggggtc cctgcgtctc 60 tggggtgggt ccgccaggct 120 cgggttcgac cacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc 357 <400> 232 gaggtgcagc tcctgtgcag ccagggaagg gcagactccg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg agccttttga tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac ctactggggt ttggtacagc aagtattcga attaacaata tcccgcgaca accgcggtat cagggaaccc <210> 233 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 233 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc ccigcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtccagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 * 89 - 146451-序列表,doc 201042039 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 234 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 234 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtccagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 235 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 235 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180- gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 236 <211> 357 <212> DNA <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 236 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctgggggglc cctgcgtctc 60
Icctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 237 <211> 357 <212> IM <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 237 90- 146451-序列表.doc 201042039 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 238 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 238
gaggtgcagc tcctgtgcag ccagggaagg acacactccg ctgcaaatga ggtcggtggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg cgccttttga tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ggtctcacag atttcggata ctgctgatcg tacatactac 180 gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 tgccgaggac accgcggtat attactgtgc gatatatacg 300 gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 239 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 239 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg cagatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 240 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 240 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attttgaata ctgctgatcg tacatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 241 <211> 357 <212> DNA <213>人工序列 <220> 146451 -序列表.doc -91 - 201042039 <223>來源於人類生殖系序列 <400> 241 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggs cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 242 <211> 357 <212> DNA <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 242 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tagatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 gstcgatggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 243 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 243 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tagatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtal 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 244 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 244 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggtatatact 300 gggcgttggg tgtcttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 245 <211> 357 <212> DNA 92- 146451-序列表.doc 201042039 <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 245 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gctatatact 300 gggcgttggg tgtcttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 246 <211> 357 <212> DNA <213>人工序列 <220>
<223>來源於人類生殖系序列 <400> 246 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gtttaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc ggtatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 247 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 247 gaggtgcagc tcctgtgcag ccagggaagg gcacactccg ctgcaaatga gggcgttggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcgaata ctgctgatcg tacatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gctatatact 300 tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 248 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來涿於人類生殖系序列 <400> 248 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata ctgctgatcg tagatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 93- 146451-序列表.doc 201042039 <210> 249 <211> 357 <212> DNA <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 249 ' gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata ctgctgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcclgcg tgccgaggac accgcggtat attacigtgc gatatatacg 300 ggicgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 250 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 250 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcgg cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcgaata cgggcgatcg tagatactac 180 gcacacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210〉 251 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 251 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata ctgctgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 252 <211> 357 <212> DNA <213>人工序列 <220> <223>來源·於人類生殖系序列 <400> 252 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggictcacag attgcgaata cgggtgatcg tagatactac 180 gcacacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 • 94· 146451-序列表.doc 201042039 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 253 <211> 357 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 253 gaggtgcagc tcctgtgcag ccagggaagg gcacacgcgg ctgcaaatga ggtcgttggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcgaata ctgctgatcg tagatactac 180 tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accacggtat attactgtgc gatatatacg 300 agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 o
<210> 254 <211> 357 <212> IM <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 254 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cggctgatcg tagatactac 180 gcacacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 255 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 255 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtciagagtg ggtctcacag attgtgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 256 <211> 357 <212> IM <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 256 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 146451·序列表.doc -95- 201042039 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcgaata cgggtgatcg tagatactac 180 gcagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 257 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 257 gaggtgcagc tsttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 258 <2】1> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 258 gaggtgcagc tgttggagtc tcctgtgcag cctccggatt ccagggaagg gtctagagtg gatcactccg tgaagggccg ctgcaaatga acagcctgcg ggtcgttgga ggccttttga tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ggtctcacag atttcggata ctgctgatcg tacatactac 180 gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 tgccgaggac accgcggtat attactgtgc gatatatacg 300 gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 259 <211> 357 <212> DNA <2】3>人工序列 <220> <223>來源於人類生殖系序列 <400> 259 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 260 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 -96- 146451-序列表.doc 201042039 <400> 260 saggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 tcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 261 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 261 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180
acacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 262 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 262 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 acagacgcgg tgaaggggcg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 263 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 263 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 264 <211> 357 <212> DNA <213>人工序列 97- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 264 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctmtg aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac gcacactccg tgaaggsccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 265 <211> 357 <212> DMA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 265 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag attgcggata cgggtgatcg tagatactac gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 266 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 266 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tagatactac gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc
<210> 267 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 267 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgcctc tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac gatcactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg aaccttttgt ctactggggt cagggaaccc tggicaccgt ctcgagc <210> 268 98- 146451-序列表.doc 201042039 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 268 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggait cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata cgggtgatcg tagatactac 180 gatgacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 269 <211> 357 <212> DNA <213>人工序列
<220> <223>來源於人類生殖系序列 <400> 269 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tagatactac 180 gatgactctg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 270 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 270 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcggata cgggtgatcg tagatactac 180 gatcactctg tgaagggccg gttcactatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 271 <211> 357 <212> EM <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 271 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcggata cgggtgatcg tagatactac 180 gatgacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 -99· 146451-序列表.doc 201042039 ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 272 <211> 357 <212> DNA <213>人工序列 <220> <Z23>來»於人類生殖系序列 <400> 272 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgU aagtattcga tggggtgggi ccgccaggct 120 ccagggaagg gtclagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg ggccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 273 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 273 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg tgccttttgc ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 274 <211> 357 <212> DNA <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 274 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttggg gaccttttca gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 275 <211> 357 <212> DNA <213>人工序列 <220> <2‘23>來源於人類生殖系序列 <400> 275 gaggtgcagc tgttaaagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 -100- 146451-序列表.doc 201042039 ccagggaagg gcacactccg ctgcaaatga ggtcgttggg gtctagagtg tgaagg£〇cg acagcctgcg agccttttca ggtctcacag gttcaccatc tgccgaggac gtactggggt atttcggata tcccgcgaca accgcggtat cagggaactc ctgctgatcg tacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc 357
<210> 276 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <>276 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc tcctgtgcag cctccggatt cacctttgtt aagtattcga ccagggaagg gtctagagtg ggtctcacag atttcggata gcacactccg tgaagggccg gttcaccatc tcccgcgaca ctgcaaatga acagcctgcg tgccgaggac accgcggtat ggtcgttggg cgccttttga gtactggggt cagggaaccc <210> 277 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 277 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc tcctgtgcag cctccggatt cacctttgtt aagtattcga ccagggaagg gtctagagtg ggtctcacag atttcggata gcacactccg tgaagggccg gttcaccatc tcccgcgaca ctgcaaatga acagcctgcg tgccgaggac accgcggtat ggtcgttggg cgccttttca gtactggggt cagggaactc
<210> 278 <21i> 357 <212> IM <213>人工序列 <220> <223>來沐於人類生殪系序列 ctggggggtc cctgcgtctc 60 tggggtgggt ccgccaggct 120 ctgctgatcg tacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc 357 ctggggggtc cctgcgtctc 60 tggggtgggt ccgccaggct 120 ctgctgatcg tacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc 357 ctggggggtc cctgcgtctc 60 tggggtgggt ccgccaggct 120 ctgctgatcg tacatactac 180 attccaagaa cacgctgtat 240 attactgtgc gatatatacg 300 tggtcaccgt ctcgagc 357 <400> 278 gaggtgcagc tcctgtgcag ccagggaagg gcacactccg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg tgccttttca tgggggaggc cacctttgtt ggtctcacag gttcaccatc tgccgaggac gtactggggt ttggtacagc aagtattcga atttcggata tcccgcgaca accgcggtat cagggcaccc <210> 279 <211> 357 <212> DNA <213>人工序列 <220> <223>來涿於人類生殖系序列 -101 - 146451-序列表.doc 201042039 <400> 279 gaggtgcagc tcctgtgcag ccagggaagg gatcactctg cigcaaatga ggtcggtggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcggata ccggtgatcg tagatactac 180 tgaagggccg gttcactatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 280 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 280 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttg aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg igctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 281 <211> 357 <212> DNA <213>人工序列 <220> <_223>來源於人類生殖系序列 <400> 281 gaggtgcagc tgttggagtc igggggaggc 丨tggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgcctutga gUctggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 282 <21i> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 282 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 icctgtgcag cctccggatt cacctttttg aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtclcacag atttcggata ctgctgatcg tacatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat altactgtgc gatatatacg 300 ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 283 <211> 357 <212> DNA <213>人工序列 102- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 283 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcgttgga ggccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 284 <211> 357 <212〉腿 <213>人工序列 <220> <223>來源於人類生殖系序列
<400> 284 gaggtgcagc tcctgtgcag ccagggaagg gatcactccg ctgcaaatga ggtcgttggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cciccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 285 <21i> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列
<400> 285 gaggtgcagc tcctgtgcag ccagggaagg gatcactccg ctgcaaatga ggtcgttggg tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttttg aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 286 <211> 357 <212> I^IA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 286 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttg aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 tcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 287 <211> 357 146451-序列表.doc 103 - 201042039 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 287 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 tcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 288 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 288 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtaitcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 acacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300 gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 289 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 289 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttg aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 acacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact 300
Sggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 290 <211> 357 <212〉IM <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 290 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gataiatacg 300 ggtcgttggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 •104- 146451-序列表.doc 201042039 <210> 291 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 291 gaggtgcagc tcctgtgcag ccagggaagg gcacactccg ctgcaaatga ggtcgttggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg cgccttttga tgggggaggc cacctttttg ggtctcacag gttcaccatc tgccgaggac gtactggggt ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcggata ctgctgatcg tacatactac ISO tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 <210> 292 <211> 357 <212> DNA <213>人工序列 Ο <220> <223>來源於人類生殖系序列 ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcggata ccggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 <400> 292 gaggtgcagc tcctgtgcag ccagggaagg gatcactctg ctgcaaatga ggtcggtggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg cgccttttga tgggggaggc cacctttttg ggtctcacag gttcactatc tgccgaggac gtactggggt <210> 293 <211> 357 <212> DNA <213>人工序列 <220> <223>來涿於人類生殖系序列
ttggtacagc ctggggggtc cctgcgtctc 60 aagtattcga tggggtgggt ccgccaggct 120 atttcggata ccggtgatcg tagatactac 180 tcccgcgaca attccaagaa cacgctgtat 240 accgcggtat attactgtgc gatatatacg 300 cagggaaccc tggtcaccgt ctcgagc 357 <400> 293 gaggtgcagc tcctgtgcag ccagggaagg gatcactctg ctgcaaatga ggtcggtggg tgttggagtc cctccggatt gtctagagtg tgaagggccg acagcctgcg cgccttttga tgggggaggc cacctttttc ggtctcacag gttcactatc tgccgaggac gtactggggt <210> 294 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 294 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tacatactac 180 -105- 146451·序列表.doc 201042039 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgcgc gatatatact gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 295 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 295 gaggtscagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttttt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tacatactac gcacacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 296 <211〉 357 <212> 臟 <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 296 gaggtgcagc tgttggagtc tgggggaggc ttggtgcagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tacatactac gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgctgaggac accgcggtat attactgtgc gatatatact gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 297 <211> 357 <212> DNA <213>人工序列 <220> 來源於人類生殖系序列 <400> 297 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tacatactac gatcacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat cigcaaatga acagcclgcg tgctgaggac accgcggtat attactgtgc gatatatact gggcgttggg tgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc <210> 298 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 298 106· 146451-序列表.doc 201042039 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tagatactac 180 gcacactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<210> 299 <211> 357 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 299 gaggtgcagc tcctgtgcag ccagggaagg gcacacgcgg ctgcaaatga ggtcggtggg
tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 gtctagagtg ggtctcacag atttcggata ctgctgatcg tagatactac 180 tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 300 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 300 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tagatactac 180 gcacacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357
<21Q> 301 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 301 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tagatactac 180 gatcacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg 300 ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc 357 <210> 302 <211> 35*7 <212> im <213>人工序列 <220> 107· 146451-序列表.doc 201042039 <223>來源於人類生殖系序列 <400> 302 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tagatactac gatcacgcgg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcggtggg cgccttttga gtactggggt caggggaccc tggtcaccgt ctcgagc <210> 303 <211> 357 <212> UNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 303 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttgtt aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag attgcggata ctgctgatcg tagatactac gatcactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcggtggg cgccttttga gtactggggt cagggaaccc tggtcaccgt ctcgagc
<210> 304 <211> 357 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 304 gaggtgcagc tgctggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttttc aagtattcga tggggtgggt ccgccaggct ccagggaagg gtctagagtg ggtctcacag atttcggata ctgctgatcg tagatactac gatgacgcgg tgaagggccg gttcaccatc acccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gatatatacg ggtcgttggg agccttttgt ctactggggt cagggaaccc tggtcaccgt ctcgagc <210> 305 <211〉 163 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 305
His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 15 10 15
Glu Ala Val Arg Leu Phe lie Glu Trp Leu Lys Asn Gly Gly Pro Ser 20 25 30
Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45
Gly Ser Gly Gly Gly Gly Ser Asp lie Gin Met Thr Gin Ser Pro Ser 5〇 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg Ala 65 70 75 80 -108- 146451-序列表.doc 201042039
Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser Leu Gin Ser Gly 100 105 110
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 115 120 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140
Gin Gly Ala Ala Leu Pro Arg Thr Phe Gly Gin Gly Thr Lys Val Glu 145 150 155 160
He Lys Arg <210> 306 <211> 489 <212〉 DNA <213>人工序列 <220>
<223>來源於人類生殖系序列 <400> 306 catggtgaag gaacatttac cagtgacttg tcaaaacaga tggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gttcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc 180 cagtctccat cctccctgtc tgcatctgta ggagaccgtg tcaccatcac ttgccgggca 240 agtcagtgga ttgggtctca gttatcttgg taccagcaga aaccagggaa agcccctaag 300 ctcctgatca tgtggcgttc ctcgttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgtg ctcagggtgc ggcgttgcct aggacgttcg gccaagggac caaggtggaa 480 atcaaacgg 489 <210> 307 <211> 163 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 307
His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 15 10 15
Glu Ala Val Arg Leu Phe lie Glu Trp Leu Lys Asn Gly Gly Pro Ser 20 25 30
Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45
Gly Ser Gly Gly Gly Gly Ser Asp He Gin Met Thr Gin Ser Pro Ser 50 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg Ala 65 70 75 80
Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser Leu Gin Ser Gly 100 105 110
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 115 120 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140
Gin Gly Leu Arg His Pro Lys Thr Phe Gly Gin Gly Thr Lys Val Glu -109- 146451-序列表.doc 201042039 145 150 155 160 lie Lys Arg <210> 308 <211> 489 <212> DNA <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 308 catggtgaag gaacatttac cagtgacttg tcaaaacaga iggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gitcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc 180 cagtctccat cctccctgtc tgcatctgta ggagaccatg tcaccatcac ttgccgggca 240 agtcagtgga ttggstctca gttatcttgg taccagcaga aaccagggaa agcccctaag 300 ctcctgatca tgtggcgttc ctcgttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgtg ctcagggttt gaggcatcct aagacgitcg gccaagggac caaggtggaa 480 atcaaacgg 4S9 <210> 309 <211> 163 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 309
His G]y Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 15 10 15
Glu Ala Val Arg Leu Phe lie Glu Trp Leu Lys Asn Gly Gly Pro Ser 20 25 30
Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45
Gly Ser Gly Gly Gly Gly Ser Asp lie Gin Met Thr Gin Ser Pro Ser 50 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg Ala 65 70 75 80
Ser Gin Trp He Gly Ser Gin Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser Leu Gin Ser Gly 100 105 110
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 115 120 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140
Gin Gly Leu Met Lys Pro Met Thr Phe Gly Gin Gly Thr Lys Val Glu 145 150 155 160 lie Lys Arg <210> 310 <211> 489 <212> DNA <213>人工序列 1】0· 14645丨-序列表 201042039 <220> <223>來濰於人類生殖系序列 <400> 310 catggtgaag gaacatttac cagtgacttg tcaaaacaga tggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gttcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc 180 cagtctccat cctccctgtc tgcatctgta ggagaccgtg tcaccatcac ttgccgggca 240 agtcagtgga ttgggtctca gttatcttgg taccagcaga aaccagggaa agcccctaag 300 ctcctgatca tgtggcgttc ctcgttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgtg ctcagggtct tatgaagcct atgacgttcg gccaagggac caaggtggaa 480 atcaaacgg 489 <210> 311 <211> 163 <212> PRT <213>人工序列 <220> Ο <223>來源於人類生殖系序列 <400> 311
His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 15 10 15
Glu Ala Val Arg Leu Phe lie Glu Trp Leu Lys Asn Gly Gly Pro Ser 20 25 30
Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45
Gly Ser Gly Gly Gly Gly Ser Asp lie Gin Met Thr Gin Ser Pro Ser 50 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Ser Cys Arg Ala 65 70 75 80
Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Glu Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser Leu Gin Ser Gly 100 105 110
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 115 120 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140
Gin Gly Ala Ala Leu Pro Arg Thr Phe Gly Gin Gly Thr Lys Val Glu 145 150 155 160 lie Lys Arg <210> 312 <211> 489 <212> mk <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 312 catggtgaag gaacatttac cagtgacttg tcaaaacaga tggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gttcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc 180 cagtctccat cctccctgtc tgcatctgta ggagaccgtg tcaccatctc ttgccgggca 240 111 - 146451 -序列表.doc 201042039 agtcagtgga ttgggtctca gttatcttgg taccagcaga aaccagggga agcccctaag 300 ctcctgatca tgtggcgttc ctcgttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgtg ctcagggtgc ggcgttgcct aggacgttcg gccaagggac caaggtggaa 480 atcaaacgg 489 <210> 313 <211> 163 <212> m <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 313
His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 15 10 15
Glu Ala Val Arg Leu Phe lie Glu Trp Leu Lys Asn Gly Gly Pro Ser 20 25 30
Ser G3y Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45
Gly Ser Gly Gly Gly Gly Ser Asp He Gin Met Thr Gin Ser Pro Ser 50 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg Ala 65 70 75 80
Ser Arg Pro lie Gly Thr Thr Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Lys Ala Pro Lys Leu Leu lie Trp Phe Gly Ser Arg Leu Gin Ser Gly 100 105 110
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 115 120 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140 GJn Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly Thr Lys Va] G]u 145 150 155 160 lie Lys Arg <210> 314 <211> 489 <212> ΕλΝΑ <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 314 catggtgaag gaacatttac cagtgacttg tcaaaacaga tggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gttcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc 180 cagtctccat cctccctgtc tgcatctgta ggagaccgtg tcaccatcac ttgccgggca 240 agtcgtccga ttgggacgac gitaagttgg taccagcaga aaccagggaa agcccctaag 300 ctcctgatct ggtttggttc ccggttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgtg cgcaggctgg gacgcatcct acgacgtteg gccaagggac caaggtggaa 480 atcaaacgg 489
<210> 315 <211〉 163 <212> PRT 112- 146451·序列表.doc 201042039 <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 315
His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 1 5 10 15
Glu Ala Val Arg Leu Phe lie Glu Trp Leu Lys Asn Gly Gly Pro Ser 20 25 30
Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45
Gly Ser Gly Gly Gly Gly Ser Asp lie Gin Met Thr Gin Ser Pro Ser 50 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg Ala 65 70 75 80
Ser Arg Pro lie Gly Thr Met Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Lys Ala Pro Lys Leu Leu lie Leu Phe Gly Ser Arg Leu Gin Ser Gly 100 105 110 Ο
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 115 1+20 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140
Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly Thr Lys Val Glu 145 150 155 160 lie Lys Arg <210> 316 <211> 489 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 316 catggtgaag gaacatttac cagtgacttg tcaaaacaga tggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gttcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc ISO cagtctccat cctccctgtc tgcatctgta ggagaccgtg tcaccatcac ttgccgggca 240 agtcgtccga ttgggacgat gttaagttgg taccagcaga aaccagggaa agcccctaag 300 ctcctgatct tgtttggttc ccggttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgtg cgcaggctgg gacgcatcct acgacgttcg gccaagggac caaggtggaa 480 atcaaacgg 489 <210> 317 <211> 163 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 317
His Glv Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gin Met Glu Glu 15 10 15
Glu Ala Val Arg Leu Phe He Glu Trp Leu Lys Asn Gly Gly Pro Ser • 113· 146451·序列表.doc 201042039 20 25 30
Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly 35 40 45 G]y Ser Gly Gly Gly Gly Ser Asp He Gin Met Thr Gin Ser Pro Ser 50 55 60
Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg Ala 65 70 75 80
Ser Arg Pro lie Gly Thr Met Leu Ser Trp Tyr Gin Gin Lys Pro Gly 85 90 95
Lys Ala Pro Lys Leu Leu lie Leu Ala Phe Ser Arg Leu Gin Ser Gly 100 105 110
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Lea 115 120 125
Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala 130 135 140
Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly Thr Lys Val Glu 145 150 155 160 lie Lys Arg <210> 318 <211> 489 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 318 catggtgaag gaacatttac cagtgacttg tcaaaacaga tggaagagga ggcagtgcgg 60 ttatttattg agtggcttaa gaacggagga ccaagtagcg gggcacctcc gccatcgggt 120 ggtggaggcg gttcaggcgg aggtggcagc ggcggtggcg ggtcggacat ccagatgacc 180 cagtctccat cctccctgtc tgcatctgta ggagaccgtg tcaccatcac ttgccgggca 240 agtcgtccga ttgggacgat gttaagttgg taccagcaga aaccagggaa agcccctaag 300 ctcctgatcc ttgctttttc ccgtttgcaa agtggggtcc catcacgttt cagtggcagt 360 ggatctggga cagatttcac tctcaccatc agcagtctgc aacctgaaga ttttgctacg 420 tactactgcg cgcaggctgg gacgcatcct acgacgttcg gccaagggac caaggtggaa 480 atcaaacgg 489
<210> 319 <211> 114 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 319
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr He Thr Cys Arg Ala Ser Gin Trp He Gly Ser Gin 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Met Trp Arg Ser Ser Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Gly Leu Arg His Pro Lys 85 90 95 -114* 14645卜序列表.doc 201042039
Thr Phe Gly Gin Gly Thr Lys Val Glu He Lys Arg Gly Gly Gly Gly 100 105 110
Ser Cys <210> 320 <211> 345 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 320 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtca gtggattggg tctcagttat cttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatcatgtgg cgttcctcgt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgtgctcag ggtttgaggc atcctaagac gttcggccaa 300
〇 gggaccaagg tggaaatcaa acggggtggc ggagggggtt cctgt 345 <210> 321 <211> 115 <212> PRT <213>人工序列 <2'20> <223〉來源於人類生殖系序列 <400〉 321
Asp He Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr He Thr Cys Arg Ala Ser Gin Trp lie Gly Ser Gin 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Met Trp Arg Ser Ser Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Gly Leu Arg His Pro Lys 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg Thr Val Ala Ala 100 105 110
Pro Ser Cys 115 <210> 322 <21I> 345 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 322 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtca gtggattggg tctcagttat cttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatcatgtgg cgttcctcgt tgcaaagtgg ggtcccatca 180 •115- 146451-序列表.doc 201042039 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgtgctcag ggtttgaggc atcctaagac gttcggccaa 300 gggaccaagg tggaaatcaa acggaccgtc gctgctccat cttgt 345 <210> 323 <211〉 235 <212> PRT <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 323
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Arg Tyr 20 25 30
Ser Met Gly Trp Leu Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Arg lie Asp Ser Tyr Gly Arg Gly Thr Tyr Tyr Glu Asp Pro Val 50 55 60
Lys Gly Arg Phe Ser lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys lie Ser Gin Phe Gly Ser Asn A]a Phe Asp Tyr Trp Gly Gin 100 105 110
Gly Thr Gin Val Thr Va] Ser Ser Ala Ser Thr Ser Gly Pro Ser Asp 115 120 125 lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 130 135 140
Arg Val Thr He Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Thr Leu 145 150 155 160
Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Trp 165 170 175
Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 180 185 190 G]y Ser Gly Thr Asp Phe Thr Leu Thr I]e Ser Ser Leu Gin Pro Glu 195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr 210 215 220
Phe Gly Gin Gly Thr Lys Val Glu He Lys Arg 225 230 235 <210> 324 <211> 249 <212〉 PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 324
Glu Val Gin Leu Leu Glu Ser Gly G]y Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Arg Tyr 20 25 30
Ser Met Gly Trp Leu Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Arg lie Asp Ser Tyr Gly Arg Gly Thr Tyr Tyr Glu Asp Pro Val -116- 14645卜序列表.doc 201042039 50 55 60
Lys Gly Arg Phe Ser lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys lie Ser Gin Phe Gly Ser Asn Ala Phe Asp Tyr Trp Gly Gin 100 105 no
Gly Thr Gin Val Thr Va] Ser Ser Ala Ser Thr Ser Gly Pro Ser Asp 115 120 125
He Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 130 135 140
Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Thr Leu 145 150 155 160
Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Lea lie Trp 165 170 175
Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser ISO 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu 195 200 205 ❹
Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr 210 215 220
Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin 225 230 235 240
Lys Leu lie Ser Glu Glu Asp Leu Asn 245 <210> 325 <211> 705 <212> DNA <213>人工序列 <220> <223>來涿於人類生殖系序列 <400> 325 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttaat aggtatagta tggggtggct ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacgg attgattctt atggtcgtgg tacatactac 180 gaagaccccg tgaagggccg gttcagcatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgccgtat attactgtgc gaaaatttct 300 cagtttgggt caaatgcgtt tgactactgg ggtcagggaa cccaggtcac cgtctcgagc 360 gctagcacca gtggtccatc ggacatccag atgacccagt ctccatcctc cctgtctgca 420 tctgtaggag accgtgtcac catcacttgc cgggcaagtc gtccgattgg gacgacgtta 480 agttggtacc agcagaaacc agggaaagcc cctaagctcc tgatctggtt tggttcccgg 540 ttgcaaagtg gggtcccatc acgtttcagt ggcagtggat ctgggacaga tttcactctc 600 accatcagca gtctgcaacc tgaagatttt gctacgtact actgtgcgca ggctgggacg 660 catcctacga cgttcggcca agggaccaag gtggaaatca aacgg 705 <210> 326 <211〉 750 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 326 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttaat aggtatagta tggggtggct ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacgg attgattctt atggtcgtgg tacatactac 180 •117· 146451-序列表.doc 201042039 gaagaccccg tgaagggccg gttcagcatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgccgtat attactgtgc gaaaatttct cagtttgggt caaatgcgtt tgactactgg ggtcagggaa cccaggtcac cgtctcgagc gctagcacca gtggtccatc ggacatccag atgacccagt ctccatcctc cctgtctgca tctgtaggag accgtgtcac catcacttgc cgggcaagtc gtccgattgg gacgacgtta agttggtacc agcagaaacc agggaaagcc cctaagctcc tgatctggtt tggttcccgg ttgcaaagtg gggtcccatc acgtttcagt ggcagtggat ctgggacaga tttcactctc accatcagca gtctgcaacc tgaagatttt gctacgtact actgtgcgca ggctgggacg catcctacga cgttcggcca agggaccaag gtggaaatca aacgggcggc cgcagaacaa aaactcatct cagaagagga tctgaattaa <210> 327 <211> 235 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 327
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Arg Tyr 20 25 30
Ser Met Gly Trp Leu Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Arg lie Asp Ser Tyr Gly Arg G】y Thr Tyr Tyr G]u Asp Pro Val 50 55 60
Lys Gly Arg Phe Ser lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys lie Ser Gin Phe Gly Ser Asn Ala Phe Asp Tyr Trp Gly Gin 100 105 110
Gly Thr Gin Val Thr Val Ser Ser Ala Ser Thr Ser Gly Pro Ser Asp 115 120 125 lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 130 135 140
Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met Leu 145 150 155 160
Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu 165 170 175
Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu 195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr 210 215 220
Phe Gly Gin Gly Thr Lys Va] Glu I]e Lys Arg 225 230 235 <210> 328 <211> 249 <212> PRT <213>人工序列 <220> <2_23>來源於人類生殖系序列 <4〇〇> 328 118- 146451-序列表.doc 201042039
Glu Va3 Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Arg Tyr 20 25 30
Ser Met Gly Trp Leu Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Arg lie Asp Ser Tyr Gly Arg Gly Thr Tyr Tyr Glu Asp Pro Val 50 55 60
Lys Gly Arg Phe Ser lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys lie Ser Gin Phe Gly Ser Asn Ala Phe Asp Tyr Trp Gly Gin 100 105 110
Gly Thr Gin Val Thr Val Ser Ser Ala Ser Thr Ser Gly Pro Ser Asp 115 120 125
He Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 130 135 140
Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met Leu 145 150 155 160
Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu 165 170 175
Phe Gly Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu 195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr 210 215 220
Phe Gly Gin Gly Thr Lys Val Glu He Lys Arg Ala Ala Ala Glu Gin 225 230 235 240
Lys Leu lie Ser Glu Glu Asp Leu Asn 245 <210> 329 <211> 705 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 329 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttaat aggtatagta tggggtggct ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacgg attgattctt atggtcgtgg tacatactac 180 gaagaccccg tgaagggccg gttcagcatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgccgtat attactgtgc gaaaatttct 300 cagtitgggt caaatgcgtt tgactactgg ggtcagggaa cccaggtcac cgtctcgagc 360 gctagcacca gtggtccatc ggacatccag atgacccagt ctccatcctc cctgtctgca 420 tctgtaggag accgtgtcac catcacttgc cgggcaagtc gtccgattgg gacgatgtta 4S0 agttggtacc agcagaaacc agggaaagcc cctaagctcc tgatcttgtt tggttcccgg 540 ttgcaaagtg gggtcccatc acgtttcagt ggcagtggat ctgggacaga tttcactctc 600 accatcagca gtctgcaacc tgaagatttt gctacgtact actgtgcgca ggctgggacg 660 catcctacga cgttcggcca agggaccaag gtggaaatca aacgg 705
<210> 330 <211〉 750 <212> DNA <213>人工序列 119- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 330 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt caccittaat aggtatagta iggggtggct ccgccaggct ccagggaagg gtctagagtg ggtctcacgg attgattctt atggtcgtgg tacatactac gaagaccccg tgaagggccg gttcagcatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgccgtat attactgtgc gaaaatttct cagtttgggt caaatgcgtt tgactactgg ggtcagggaa cccaggtcac cgtctcgagc gctagcacca gtggtccatc ggacatccag atgacccagt ctccatcctc cctgtctgca tctgtaggag accgtgtcac catcacttgc cgggcaagtc gtccgattgg gacgatgtta agttggtacc agcagaaacc agggaaagcc cctaagctcc tgatcttgtt tggttcccgg ttgcaaagtg gggtcccatc acgtttcagt ggcagtggat ctgggacaga tttcactctc accatcagca gtctgcaacc tgaagatttt gctacgtact actgtgcgca ggctgggacg catcctacga cgttcggcca agggaccaag gtggaaatca aacgggcggc cgcagaacaa aaactcatct cagaagagga tctgaattaa <210> 331 <211> 235 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 331
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Arg Tyr 20 25 30
Ser Met Gly Trp Leu Arg Gin A]a Pro G]y Lys Gly Leu Glu Trp Val 35 40 45
Ser Arg lie Asp Ser Tyr Gly Arg Gly Thr Tyr Tyr Glu Asp Pro Val 50 55 60
Lys Gly Arg Phe Ser lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys He Ser Gin Phe Gly Ser Asn Ala Phe Asp Tyr Trp Gly Gin 100 105 110
Gly Thr Gin Val Thr Val Ser Ser Ala Ser Thr Ser Gly Pro Ser Asp 115 120 125
He Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 130 135 140
Arg Val Thr He Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met Leu 145 150 155 160
Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu 165 170 175
Ala Phe Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr He Ser Ser Leu Gin Pro Glu 195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr 210 215 220
Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 225 230 235 <210> 332 <211> 249 120- 146451-序列表.doc 201042039 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 332
Glu Val Gin Leu Leu Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Arg Tyr 20 25 30
Ser Met Gly Trp Leu Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45
Ser Arg lie Asp Ser Tyr Gly Arg Gly Thr Tyr Tyr Glu Asp Pro Val 50 55 60
Lys Gly Arg Phe Ser lie Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 75 80
Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95
Ala Lys lie Ser Gin Phe Gly Ser Asn Ala Phe Asp Tyr Trp Gly Gin 100 105 HO
Gly Thr Gin Val Thr Val Ser Ser Ala Ser Thr Ser Gly Pro Ser Asp 115 120 125 lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 130 135 140
Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met Leu 145 150 155 160
Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu 165 170 175
Ala Phe Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu 195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr 210 215 220
Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin 225 230 235 240
Lys Leu lie Ser Glu Glu Asp Leu Asn 245 <210> 333 <211> 705 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 333 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttaat aggtatagta tggggtggct ccgccaggct 120 ccagggaagg gtctagagtg ggtctcacgg attgattctt atggtcgtgg tacatactac 180 gaagaccccg tgaagggccg gttcagcatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgccgtat attactgtgc gaaaatttct 300 cagtttgggt caaatgcgtt tgactactgg ggtcagggaa cccaggtcac cgtctcgagc 360 gctagcacca gtggtccatc ggacatccag atgacccagt ctccatcctc cctgtctgca 420 tctgtaggag accgtgtcac catcacttgc cgggcaagtc gtccgattgg gacgatgtta 480 agttggtacc agcagaaacc agggaaagcc cctaagctcc tgatccttgc tttttcccgt 540 ttgcaaagtg gggtcccatc acgtttcagt ggcagtggat ctgggacaga tttcactctc 600 accatcagca gtctgcaacc tgaagatttt gctacgtact actgcgcgca ggctgggacg 660 -121 - 146451-序列表.doc 201042039 catcctacga cgttcggcca agggaccaag gtggaaatca aacgg <210> 334 <'211> 750 <212> DNA <‘213>人工序列 <220> <223>來源於人類生殖系序列 <400> 334 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc tcctgtgcag cctccggatt cacctttaat aggtatagta tggggtggct ccgccaggct ccagggaagg gtctagagtg ggtctcacgg attgattctt atggtcgtgg tacatactac gaagaccccg tgaagggccg gttcagcatc tcccgcgaca attccaagaa cacgctgtat ctgcaaatga acagcctgcg tgccgaggac accgccgtat attactgtgc gaaaatttct cagtttgggt caaatgcgtt tgactactgg ggtcagggaa cccaggtcac cgtctcgagc gctagcacca gtggtccatc ggacatccag atgacccagt ctccatcctc cctgtctgca tctgtaggag accgtgtcac catcacttgc cgggcaagtc gtccgattgg gacgatgtta agttggtacc agcagaaacc agggaaagcc cctaagctcc tgatccttgc tltttcccgt ttgcaaagtg gggtcccatc acgtttcagt ggcagtggat ctgggacaga tttcactctc accatcagca gtctgcaacc tgaagatttt gctacgtact actgcgcgca ggctgggacg catcctacga cgttcggcca agggaccaag gtggaaatca aacgggcggc cgcagaacaa aaactcatct cagaagagga tctgaattaa <210> 335 <21i> 9 <212> PRT <‘213>智人 <400> 335
Ser Gin Ser lie Ser Ser Tyr Leu Asn 1 5 <210> 336 <211> 8 <212> PRT <213>智人 <400> 336
Tyr Ala Ala Ser Ser Leu Gin Ser 1 5 <210> 337 <211> 9 < m> PRT <213〉智人 <400> 337
Gin Gin Ser Tyr Ser Thr Pro Asn Thr 1 5
<210> 338 <211> 9 <212> PRT 122· 146451-序列表.doc 201042039 <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 338
Ser Arg Pro lie Gly Thr Thr Leu Ser 1 5 <210> 339 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 339
Trp Phe Gly Ser Arg Leu Gin Ser
<210> 340 <211> 9 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 340
Ala Gin Ala Gly Thr His Pro Thr Thr 1 5 <210> 341 <211> 9 <212> PRT <213>人工序列
<220> <223>來源於人類生殖系序列 <400> 341
Ser Arg Pro He Gly Thr Met Leu Ser 1 5 <210> 342 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 342
Leu Phe Gly Ser Arg Leu Gin Ser 1 5 -123 146451-序列表.doc 201042039 <210> 343 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 343
Ala G]n Ala Gly Thr His Pro Thr Tlir 1 5 <210> 344 <211> 9 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <4〇〇> 344
Ser Arg Pro lie Gly Thr Met Leu Ser 1 5 <210> 345 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 345
Leu Ala Phe Ser Arg Leu G3n Ser 1 5 <210> 346 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 346
Ala Gin Ala Gly Thr His Pro Thr Thr 1 5 <210> 347 <211> 9 <212> PRT <2i3>人工序列 <220> c223>來源於人類生殖系序列 -124 146451-序列表.doc 201042039 <4〇〇> 347
Ser Arg Pro lie Gly Thr Met Leu Ser 1 5 <210> 348 <211> B <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <4〇〇> 348
Trp Phe Gly Ser Arg Leu Gin Ser 1 5
<210> 349 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 349
Ala Gin Ala Gly Thr His Pro Thr Thr 1 5 <210> 350 <211> 9 <212> PRT <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 350
Ser Arg Pro lie Gly Thr Met Leu Ser ❹ 1 5 <210> 351 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 351
Leu Phe Gly Ser Arg Leu Gin Ser <210> 352 <211> 9 <212> PRT <213>人工序列 -125 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 352
Ala Gin Thr Gly Thr His Pro Thr Thr 1 5 <210> 353 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 353
Ser Arg Pro lie Gly Thr Thr Leu Ser 1 5 <210> 354 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 354
Leu Trp Phe Ser Arg Leu Gin Ser 1 5 <210> 355 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 355
Ala Gin Ala Gly Thr His Pro Thr Thr 1 5 <210> 356 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 356
Ser Gin Trp He Gly Ser Gin Leu Ser 1 5 126- 14645卜序列表.doc 201042039 <210> 357 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 357
Met Trp Arg Ser Ser Leu Gin Ser 1 5 <210> 358 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 〇 <400> 358
Ala Gin G]y Ala Ala Leu Pro Arg Thr 1 5 <210> 359 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 359
Ser Gin Trp He Gly Ser Gin Leu Ser 1 5
<210> 360 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 360
Met Trp Arg Ser Ser Leu Gin Ser 1 5 <210> 361 <211> 9 <212〉 PRT <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 361 -127- 146451-序列表.doc 201042039
Ala Gin Gly Leu Arg His Pro Lys Thr 1 5 <210> 362 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 362
Ser Gin Trp lie Gly Ser Gin Leu Ser 1 5 <210> 363 <211> 8 <212> PRT <213〉人工序列 <220〉 <223〉來源於人類生殖系序列 <400> 363
Met Trp Arg Ser Ser Leu Gin Ser 1 5 <210> 364 <211> 9 <212> PRT <213〉人工序列 <220〉 <223>來源於人類生殖系序列 <400> 364
Ala Gin Gly Leu Met Lys Pro Met Thr 1 5 <210> 365 <211> 9 <212> PRT <2]3>人工序列 <220> <223>來源於人類生殖系序列 <400> 365
Ser Gin Trp lie Gly Ser Gin Leu Ser 2 5 <210> 366 <211> 8 <212> PRT <213>人工序列 128 146451·序列表.doc 201042039 <220〉 <223>來源於人類生殖系序列 <400> 366
Met Trp Arg Ser Ser Leu Gin Ser 1 5 <210> 367 <211> 9 <212〉 PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 367
Ala Gin Gly Ala Ala Leu Pro Arg Thr 1 5
<210> 368 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 368
Ser Gin Trp lie Gly Ser Gin Leu Ser 1 5 <210> 369 <211> 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 369
Met Trp Arg Ser Ser Leu Gin Ser 1 5 <210> 370 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 370
Ala Gin Gly Ala Ala Leu Pro Lys Thr 1 5 <210> 371 -129- 146451-序列表.doc 201042039 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 371
Ser Gin Trp lie Gly Ser Gin Leu Ser 1 5 <210> 372 <211〉 8 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 372
Met Trp Arg Ser Ser Leu Gin Ser 1 5 <210> 373 <211> 9 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 373 A]a Gin Gly Phe Lys Lys Pro Arg Thr 1 5 <210> 374 <21I> 165 <212> PRT <213>智人 <400> 374
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met I 5 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro G]n Glu G3u Phe G]y Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 BO
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125 130- U6451-序列表.doc 201042039
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140 Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160 Leu Arg Ser Lys Glu 165 <210〉 375 <211> 495 <212> DNA <213〉智人 <400〉 375
tgtgatctgc ctcaaaccca atgaggagaa tctctctttt gaggagtttg gcaaccagtt cagcagatct tcaatctctt ctagacaaat tctacactga cagggggtgg gggtgacaga aaatacttcc aaagaatcac gaggttgtca gagcagaaat ttaagaagta aggaa cagcctgggt agcaggagga ccttgatgct cctggcacag 60 ctcctgcttg aaggacagac atsactttgg atttccccag 120 ccaaaaggct gaaaccatcc ctgtcctcca tgagatgatc 180 cagcacaaag gactcatctg ctgcttggga tgagaccctc 240 actctaccag cagctgaatg acctggaagc ctgtgtgata 300 gactcccctg atgaaggagg actccattct ggctgtgagg 360 tctctatctg aaagagaaga aatacagccc ttgtgcctgg 420 catgagatct ttttctttgt caacaaactt gcaagaaagt 480 495 <210> 376 <211> 25 <212> DNA <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 376 gcccggatcc accggctgtg atctg <210> 377 <211> 30 <212> \m <213>人工序列 25
<220> <223>來源於人類生殖系序列 <400> 377 ggaggatgga gactgggtca tctggatgtc 30 <210> 378 <211> 30 <212> <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 378 gacatccaga tgacccagtc tccatcctcc <210> 379 <211> 82 <212> Wk 146451-序列表.doc 131 - 30 201042039 <Ή3>人工序列 <220> <223>來源於人類生殖系序列 <400> 379 gcgcaagctt ttattaattc agatcctctt ctgagatgag tttttgttct gcggccgccc 60 gtttgatttc caccttggtc cc 82
<210> 380 <211> 56 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 380 gcccggatcc accggctgtg atctggcgca agcttttatt aattcagatc ctcttc 56 <210> 381 <211> 51 <212> DNA <2i3>人工序列 <220> <223>來源於人類生殖系序列 <400> 381 tgagatgagt ttttgttctg cggccgcccg tttgatttcc accttggtcc c 51 <210> 382 <211> 1 <212> PRT <213>鼠類 <400> 382 Gly <210> 383 <211> 61 <212> DNA <213〉鼠類 <400> 383 atggagaccg acaccctgct gctgtgggtg ctgctgctgt gggtgcccgg atccaccggg 60 c 61 <210> 384 <211> 293 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 384 -132- 146451-序列表.doc 201042039
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Fhe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Tlir Val Ala Ala Pro Ser Asp He Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr He 180 185 190
Thr Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr He Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Gly Ala Ala Leu Pro Arg Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin Lys Leu lie Ser 275 280 2S5
Glu Glu Asp Leu Asn 290
<210> 385 <211> 882 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 385 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcagtggatt 600 gggtctcagt tatcttggta ccagcagaaa ccagggaaag cccctaagct cctgatcatg 660 tggcgttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 -133- 146451·序列表.doc 201042039 gaittcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct 780 cagggtgcgg cgttgcctag gacgttcggc caagggacca aggtggaaat caaacgggcg 840 gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa 882 <210> 386 <211> 279 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 386
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe SerThr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Giu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu He Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr He 180 185 190
Thr Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro G]y Lys A]a Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin GJy Ala Ala Leu Pro Arg Thr Phe G3y Gin G)y 260 265 270
Thr Lys Va] Glu I]e Lys Arg 275 <210> 387 <211> 837 <212> DNA <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 387 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 -134- 146451-序列表.doc 201042039 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt itctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcaigg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcagtggatt 600 gggtctcagt tatcttggta ccagcagaaa ccagggaaag cccctaagct cctgatcatg 660 tggcgttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct 780 cagggtgcgg cgttgcctag gacgttcggc caagggacca aggtggaaat caaacgg 837 <210> 388 <211> 293 <212〉 PRT <213〉人工序列 <220>
<223>來源於人類生殖系序列 <400> 388
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 1 5 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr He Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Gly Leu Arg His Pro Lys Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin Lys Leu lie Ser 275 280 285
Glu Glu Asp Leu Asn 290 135- 146451-序列表.doc 201042039 <210> 389 <211> 882 <212> DNA <213〉人工序列 <220〉 <223>來源於人類生殖系序列 <400> 389 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcagtggatt gggtctcagt tatcttggta ccagcagaaa ccagggaaag cccctaagct cctgatcatg tggcgttcct cgttgcaaag tggggtccca tcacgttica gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct cagggtttga ggcatcctaa gacgttcggc caagggacca aggtggaaat caaacgggcg gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa <210> 390 <211> 279 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 390
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 1 5 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser 乙eu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys G]u Lys Lys Tyr Ser Pro Cys Ala Trp Glu Va] Va] Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser G3n Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 136- 14645卜序列表.doc 201042039 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys A]a Gin Gly Leu Arg His Pro Lys Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu He Lys Arg 275 <210> 391 <211> 837 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 Ο <4〇〇> 391 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttglt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatacittc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcagtggatt 600 gggtctcagt tatcttggta ccagcagaaa ccagggaaag cccctaagct cctgatcatg 660 tggcgttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccaicag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct 780 cagggtttga ggcatcctaa gacgttcggc caagggacca aggtggaaat caaacgg 837 <210> 392 <211> 293 <212> PRT <213〉人工序列
<220> <223>來源於人類生殖系序列 <400> 392
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser He Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu •137· 146451-序列表.doc 201042039 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie G)n Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val G3y Asp Arg Va] Thr He 180 185 190
Thr Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Gly Leu Met Lys Pro Met Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin Lys Leu lie Ser 275 280 285
Glu Glu Asp Leu Asn 290 <210> 393 <211> 882 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 393 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt cagggtgtag gagttactga aactccccta aigaaagaag attcaattct agccgttaga aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcagiggatt gggtctcagt tatcttggta ccagcagaaa ccagggaaag cccctaagct cctgatcatg tggc£ttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct cagggtctta tgaagcctat gacgttcggc caagggacca aggtggaaat caaacgggcg gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa <210> 394 <211> 279 <212> PRT <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 394
Cys Asp Leu Pro G3n Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met I 5 10 15 -138- 146451-序列表doc 201042039
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 1 50 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp I]e Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu G]n Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala G]n Gly Leu Met Lys Pro Met Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg 275 <210> 395 <211> S37 <212> DNA <213>人工序列
<220> <223>來源於人類生殖系序列 <400> 395 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 1δ0 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcagtggatt 600 gggtctcagt tatcttggta ccagcagaaa ccagggaaag cccctaagct cctgatcatg 660 tggcgttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct 780 cagggtctta tgaagcctat gacgttcggc caagggacca aggtggaaat caaacgg 837 <210> 396 139- 146451·序列表.doc 201042039 <211> 293 <212> PRT <213>人工序列 <220〉 <223〉來源於人類生殖系序列 <400> 396
Cys Asp Leu Pro G3n Thr His Ser Leu G]y Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe G]y Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Va] Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg He Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Ser Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Glu Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Gly Ala Ala Leu Pro Arg Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin Lys Leu lie Ser 275 280 285
Glu Glu Asp Leu Asn 290 <210> 397 <211> 882 <212> DNA <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 397 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg •140- 146451-序列表.doc 201042039 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatctctt gccgggcaag tcagtggatt 600 gggtctcagt tatcttggta ccagcagaaa ccaggggaag cccctaagct cctgatcatg 660 tggcgttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagictgcaa cctgaagatt ttgctacgta ctactgtgct 780 cagggtgcgg cgttgcctag gacgttcggc caagggacca aggtggaaat caaacgggcg 840 gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa 882
<210> 398 <211> 279 <212> PRT <2I3>人工序列 <220> Ο <223>來源於人類生殖系序列 <400> 398
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 SO
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val He Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser He Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Giu Thr Val Ala Ala Pro Ser Asp He Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Ser Cys Arg Ala Ser Gin Trp lie Gly Ser Gin Leu Ser Trp Tyr Gin 195 200 205 G]n Lys Pro Gly Glu Ala Pro Lys Leu Leu lie Met Trp Arg Ser Ser 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr He Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Gly Ala Ala Leu Pro Arg Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu He Lys Arg 275 <210> 399 <211> 837 141 - 146451 -序列表.d〇c 201042039 <212> 脆 <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 399 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtalcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatctctt gccgggcaag tcagtggatt 600 gggtctcagt tatcttggta ccagcagaaa ccaggggaag cccctaagct cctgatcatg 660 tggcgttcct cgttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgct 780 cagggtgcgg cgttgcctag gacgttcggc caagggacca aggtggaaat caaacgg 837 <210> 400 <21i> 293 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 4〇〇
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met He Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp G]u Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu G]u 85 90 95
Ala Cys Val lie Gin Gly Val G]y Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser He Leu Ala Val Arg Lys Tyr Phe Gin Arg I]e Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Va] Arg 130 135 140 A]a Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu G]n Glu Ser 145 150 155 160
Leu Arg Ser Lys G】u Thr Va] A]a A】a Pro Ser Asp I]e G]n Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ik 180 185 190
Thr Cys Arg Ala Ser Arg Pro He Gly Thr Thr Leu Ser Trp Tyr Gin 195 200 205 G]n Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Trp Phe Gly Ser Arg 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240 • 142-
146451-序列表.doc 201042039
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin Lys Leu He Ser 275 280 285
Glu Glu Asp Leu Asn 290 <210> 401 <211> 882 <212> DNA <213>人工序列 <220> <2_23>來源於人類生殖系序列 <400> 401
tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcgtccgatt 600 gggacgacgt taagttggta ccagcagaaa ccagggaaag cccctaagct cctgatctgg 660 tttggttccc ggttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgcg 780 caggctggga cgcatcctac gacgttcggc caagggacca aggtggaaat caaacgggcg 840 gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa 882 <210> 402 <211> 279 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 402
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin G]u Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met He Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg •143- 146451-序列表.doc 201042039 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp He G)n Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Thr Leu Ser Trp Tyr Gin 195 200 205 G)n Lys Pro Gly Lys A]a Pro Lys Leu Leu lie Trp Phe Gly Ser Arg 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg 275
<210> 403 <211> 837 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <4〇〇> 403 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag gaagagtitg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcgtccgatt gggacgacgt laagttggta ccagcagaaa ccagggaaag cccctaagct cctgatctgg tttggttccc ggttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgcg caggctggga cgcatcctac gacgttcggc caagggacca aggtggaaat caaacgg <210> 404 <211> 293 <212> FRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 404
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg He Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Plie Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe • 144- 146451-序列表.doc 201042039 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val He Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp He Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser Arg Pro He Gly Thr Met Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu He Leu Phe Gly Ser Arg 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu lie Lys Arg Ala Ala Ala Glu Gin Lys Leu He Ser 275 280 285
Glu Glu Asp Leu Asn 290 <210> 405 <211> 882 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列
<400> 405 tgcgacttgc cacagacaca iagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300 cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcgtccgatt 600 gggacgatgt taagttggta ccagcagaaa ccagggaaag cccctaagct cctgatcttg 660 tttggttccc ggttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgcg 780 caggctggga cgcatcctac gacgttcggc caagggacca aggtggaaat caaacgggcg 840 gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa 882
<210> 406 <211> 279 <212> PRT 145- 146451-序列表.doe 201042039 <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 406
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr He Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin G3n Leu Asn Asp Leu GJu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala G]u He Met Arg Ser Phe Ser Leu Ser Thr Asn Leu G3n Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met Leu Ser Trp Tyr Gin 195 200 205 GJn Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu Phe Gly Ser Arg 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu I]e Lys Arg 275 <210> 407 <211> 837 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 407 tgcgacttgc cacagacaca tagittggga tcaagaagaa cattgatgtt attagcacaa atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt cagggtgtag gagttactga aactccccta aigaaagaag attcaatict agccgttaga aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 146· 146451-序列表.doc 201042039 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcgtccgatt 600 gggacgatgt taagttggta ccagcagaaa ccagggaaag cccctaagct cctgatcttg 660 ittggttccc ggttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgtgcg 780 caggctggga cgcatcctac gacgttcggc caagggacca aggtggaaat caaacgg 837 <210> 408 <211> 293 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 408
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin GIu Glu Phe Gly Asn Gin Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin G)n lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin Gin Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val lie Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg lie Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175
Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie 180 185 190
Thr Cys Arg Ala Ser Arg Pro He Gly Thr Met Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu Ala Phe Ser Arg 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Phe Ala Thr 245 250 255
Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu He Lys Arg Ala Ala Ala Glu Gin Lys Leu lie Ser 275 280 285
Glu Glu Asp Leu Asn 290 <210> 409 <211> 882 <212> DNA <213>人工序列 -147- 146451-序列表.doc 201042039 <220> <223>來源於人類生殖系序列 <400> 409 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgit attagcacaa atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcgtccgatt gggacgatgt taagttggta ccagcagaaa ccagggaaag cccctaagct cctgatcctt gctttttccc gtttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgcgcg caggctggga cgcatcctac gacgttcggc caagggacca aggtggaaat caaacgggcg gccgcagaac aaaaactcat ctcagaagag gatctgaatt aa <210> 410 <211> 279 <212> PRT <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 410
Cys Asp Leu Pro Gin Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met 15 10 15
Leu Leu Ala Gin Met Arg Arg lie Ser Leu Phe Ser Cys Leu Lys Asp 20 25 30
Arg His Asp Phe Gly Phe Pro Gin Glu G]u Phe Gly Asn G]n Phe Gin 35 40 45
Lys Ala Glu Thr lie Pro Val Leu His Glu Met lie Gin Gin lie Phe 50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu 65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gin G]n Leu Asn Asp Leu Glu 85 90 95
Ala Cys Val He Gin Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys 100 105 110
Glu Asp Ser lie Leu Ala Val Arg Lys Tyr Phe Gin Arg He Thr Leu 115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg 130 135 140
Ala Glu lie Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gin Glu Ser 145 150 155 160
Leu Arg Ser Lys Glu Thr Val Ala Ala Pro Ser Asp lie Gin Met Thr 165 170 175 G]n Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Tlir lie 180 185 190
Thr Cys Arg Ala Ser Arg Pro He Gly Thr Met Leu Ser Trp Tyr Gin 195 200 205
Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie Leu Ala Phe Ser Arg 210 215 220
Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 225 230 235 240
Asp Phe Thr Leu Thr lie Ser Ser Leu G]n Pro Glu Asp Phe Ala Thr 245 250 255 •148- 14645〗-序列表.doc 201042039
Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr Thr Phe Gly Gin Gly 260 265 270
Thr Lys Val Glu I]e Lys Arg 275 <210> 411 <211> 837 <212〉 DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400〉 411 tgcgacttgc cacagacaca tagtttggga tcaagaagaa cattgatgtt attagcacaa 60 atgcgtagaa tttctttgtt ctcttgtcta aaggaccgtc acgacttcgg attccctcag 120 gaagagtttg gaaaccaatt ccaaaaagca gaaactattc ctgtcttgca cgaaatgatc 180 cagcaaatat tcaatttgtt ttctacaaag gactcatcag ccgcttggga tgaaactctg 240 ttagataaat tctacactga actatatcaa caactgaacg atctagaggc ttgcgttatt 300
cagggtgtag gagttactga aactccccta atgaaagaag attcaattct agccgttaga 360 aaatactttc agcgtatcac attgtattta aaggaaaaga aatactcccc atgtgcatgg 420 gaggtggtta gagcagaaat tatgaggtcc ttctctcttt ctacgaattt gcaagaatct 480 ttgagatcta aggaaaccgt cgctgctcca tctgacatcc agatgaccca gtctccatcc 540 tccctgtctg catctgtagg agaccgtgtc accatcactt gccgggcaag tcgtccgatt 600 gggacgatgt taagttggta ccagcagaaa ccagggaaag cccctaagct cctgatcctt 660 gctttttccc gtttgcaaag tggggtccca tcacgtttca gtggcagtgg atctgggaca 720 gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgctacgta ctactgcgcg 780 caggctggga cgcatcctac gacgttcggc caagggacca aggtggaaat caaacgg 837 <210> 412 <21i> 108 <212> PRT <213>人工序列 <220〉 <223>來源於人類生殖系序列 <400> 412
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15
Asp Arg Val Thr lie Thr Cys Arg Ala Ser Gin Trp He Gly Ser Gin 20 25 30
Leu Ser Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu He 35 40 45
Met Trp Arg Ser Ser Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Gly Leu Arg His Pro Lys 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Cys 100 105 <210> 413 <211> 324 <212> DNA <213>人工序列 <220> 149· 146451 _序列表.doc 201042039 <2'23>來源於人類生殖系序列 <400> 413 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtca gtggattggg tctcagttat cttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatcatgtgg cgttcctcgt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgtgctcag ggtttgaggc atcctaagac gttcggccaa 300 gggaccaagg tggaaatcaa atgc 324 <210> 414 <211> 108 <212> PRT <213〉人工序列 <220> <223>來源於人類生殖系序列 <400> 414
Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Pro Ala Ser Val Gly 15 10 15
Asp Arg Val Thr lie Thr Cys Arg Ala Ser Arg Pro lie Gly Thr Met 20 25 30
Leu Ser Trp Tyr Ghi Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu lie 35 40 45
Leu Ala Phe Ser Arg Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gin Ala Gly Thr His Pro Thr 85 90 95
Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 100 105 <210> 415 <211> 324 <212> DNA <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 415 gacatccaga tgacccagtc tccatcctcc ctgcctgcat ctgtaggaga ccgtgtcacc 60 atcacttgcc gggcaagtcg tccgattggg acgatgttaa gttggtacca gcagaaacca 120 gggaaagccc ctaagctcct gatccttgct ttttcccgtt tgcaaagtgg ggtcccatca 180 cgtttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagattttg ctacgtacta ctgcgcgcag gctgggacgc atcctacgac gttcggccaa 300 gggaccaagg tggaaatcaa acgg 324 <210> 416 <211> 62 <212> DNA <213>人工序列 <220> <223>來源於人類生殖系序列 <400> 416 gcaacagcgt cgacggacat ccagatgacc cagtciccat cctccctgcc tgcatctgta 60 -150- 146451-序列表.doc 201042039 gg 62 <210> 417 <211> 360 <212> IM <213>人工序列 <220> <223〉來源於人類生殖系序列 <400> 417 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttagt cagtatagga tgcattgggt ccgccaggct 120 ccagggaaga gtctagagtg ggtctcaagt attgatacta ggggttcgtc tacatactac 180 gcagaccccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg Tgccgaggac accgcggtat attactgtgc gaaagctgtg 300 acgatgtttt ctcctttttt tgactactgg ggtcagggaa ccctggtcac cgtctcgagc 360
<210> 418 <211> 369 <212> IM <213>人工序列 <220> <223>來沐於人類生殖系序列 <400> 418 gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgcgtctc 60 tcctgtgcag cctccggatt cacctttgct gattatggga tgcgttgggt ccgccaggct 120 ccagggaagg gtctagagtg ggtctcatct attacgcgga ctggtcgtgt tacatactac 180 gcagactccg tgaagggccg gttcaccatc tcccgcgaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgcg tgccgaggac accgcggtat attactgtgc gaaatggcgg 300 aatcggcatg gtgagtatct tgctgatttt gactactggg gtcagggaac cctggtcacc 360 gtctcgagc 369 <210> 419 <211> 7 <212> PRT <213>人工序列 <220> <223>來涿於人類生殖系序列 <400> 419
Thr Val Ala Ala Pro Ser Cys 1 5 <210> 420 <211〉 6 <212> PRT <213>人工序列 <220> <223>合成連接子序列 <400> 420
Gly Gly Gly Gly Ser Cys 1 5 151 · 146451-序列表.doc

Claims (1)

  1. 201042039 七、申請專利範圍： 1. 一種抗血清白蛋白（S A)免疫球蛋白單一可變域D〇M7h-11(如圖1中所示之D〇M7h-ll)之變體，其中該變體與 DOM7h-11相比包含至少一個突變在F W2/CDR2接合點 (位置49至5 1，根據Kabat編號），且其中該變體與 DOM7h-11之胺基酸序列相比具有2至8個變化。 2·如請求項1之變體’其中位置49(根據Kabat)為Leu。 3.如請求項1或2之變體’其中位置5〇(根據Kabat)為Ala或 O Trp。 4_如請求項1或2之變體，其中位置51(根據Kabat)為Phe或 Asn。 5. 如請求項1之變體，其中該變體包含與選自〇〇]^711-1卜 3(SEQ ID NO: 5) ' DOM7h-11 -15(SEQ ID NO: 2) ' DOM7h-ll-12(SEQ ID NO: 1)及 DOM7h-ll-19(SEQ ID NO: 4)之單一可變域之胺基酸序列一致或與該所選胺基 酸序列相比具有多至4個變化的胺基酸序列，限制條件 〇 為該變體之該胺基酸序列具有至少一個突變在FW2/ CDR2接合點，如請求項1至4中任一項中定義。 6. 如請求項1之變體，其中該變體包含與DOM7h-ll-15sl2P(SEQ ID NO: 414)之胺基酸序列一致或與DOM7h-11-153121>之該胺基酸序列相比具有多至4個變化的胺基酸 序列，限制條件為該變體之該胺基酸序列具有至少一個 突變在FW2/CDR2接合點，如請求項1至4中任一項中定 義。 146451.doc 201042039 7. —種抗血清白蛋白（S A)免疫球蛋白單一可變域D〇M7h-11之變體，其中該變體與DOM7h-11 (如圖1中所示）相比 在位置32(根據Kabat編號）包含Met，且其中該變體與 DOM7h-ll之胺基酸序列相比具有0至4個其他變化。 8. 如請求項7之變體，其中該變體與DOM7h-l 1(如圖1中所 示）相比包含至少一個突變在FW2/CDR2接合點（位置49至 51 ’根據Kabat編號）。 9. 如請求項7之變體，其中該變體與DOM7h-ll(如圖1中所 示）相比包含至少一個選自以下之突變 位置49=L， 位置50=A或W， 位置51=F或N， 位置87=H，及 位置91=T。 10. 如請求項7之變體，其中該變體包含與選自D〇M7h-ll_ 12(SEQ ID NO: 1)、DOM7h-ll-15(SEQ ID NO: 2)、 DOM7h-ll-18(SEQ ID NO: 3)及 DOM7h-ll-19(SEQ ID NO: 4)之單一可變域之胺基酸序列一致或與該所選胺基 酸序列相比具有多至4個變化的胺基酸序列，限制條件 為該變體之該胺基酸序列在位置32具有Met。 11. 如請求項7之變體，其中該變體包含與〇〇1^711-11-15sl2p(SEQ ID NO: 414)之胺基酸序列一致或與該所選胺 基酸序列相比具有多至4個變化的胺基酸序列，限制條 件為該變體之該胺基酸序列在位置32具有Met。 146451.doc 201042039 12. 13. ❹ 14. 如請求項1、2及5至11中任一項之變體，其中該變體包 含一個結合位點以約〇. i ηΜ至約10000 ηΜ，視情況約1 ηΜ至約6000 ηΜ之解離常數（KD)特異性結合人類SA，如 表面電漿共振所測定。 如請求項1、2及5至11中任一項之變體，其中該變體包 含一個結合位點以約1.5Χ10·4 sec.1至約（u sec·1，視情況 、、'勺3 1〇 sec至約〇· 1 sec之解離速率常數（〇ff_rate constant)(Kd)特異性結合人類SA，如表面電漿共振所測 定。 如請求項1、2及5至11中任一項之變體，其中該變體包 & 個結合位點以約2χ 106 M]sec-1至約1 X 1 〇4 jy^sec·1， 視情況約1><1〇61^18 6(^1至約2乂1041^136(；-1之結合速率常 數（oiwate C〇nstant)(Ka)特異性結合人類s a，如表面電聚 共振所測定》 15. 〇 16. 如請求項1、2及5至11中任一項之變體，其中該變體包 含一個結合位點以約（Μ nM至約1〇〇〇〇 ，視情況約1 nM至約6000 nM之解離常數（KD)特異性結合獼猴 (心㈣wo/gWiS m〇nkey) SA，如表面電漿共振所測定。 如請求項1、2及5至11中任一項之變體，其中該變體包 含一個結合位點以約15x1〇-4 sey至約〇 ! 」，視情況 約3xl〇-4 seJ至約〇」sec-i之解離速率常數（Kd)特異性結 合獼猴SA ’如表面電漿共振所測定。 17. 如請求項1、2及5至11中任一 含一個結合位點以約2 X 1 〇6 M· 項之變體，其中該變體包 Secf1 至約 ixl〇4 Μ-ι sec 146451.doc 201042039 18. 19. 20. 21. 22. 23. 24. 視情況約1χ1〇6 至約5χ1〇3 Μ-、，之結合速率常 數（Ka)特異性結合獼mSA，如表面電聚共振所測定。 -種多特異性配位體，其包含如請求項】至17中任—項 之杬SA變體及特異性結合8八以外之目標抗原的結合 分。 全種如凊求項i至17中任一項之變體之抗sa變體單—可 變域，其中該可變域與藥物（視情況NCE藥物）接合，視 清况其中S亥所選變體為£)〇]^7]1_11_15(8£卩ID 2) DOM7h-n-15-(SEQ ID N〇： 4 14)^ DOM7h-Π-!2(SE〇 ID NO: 1)。 V -種融合蛋白，其包含多肽或肽藥物融合於如請求们 至17中任—項之變體’視情況其中該所選變體為 D〇M7h-ll-15(SEQ ID NO： 2) . DOM7h-11 - 1 (SEQ lD NO: 414)或 DOM7h_u_12(SEQ m n〇: 〇。 如明求項20之融合蛋白，其中該融合蛋白在該變體與該 藥物之間包含連接子（例如包含胺基酸序列tva，視情況 TVAAPS之連接子）。 種組合物，其包含如請求項1至17中任一項之變體、 如=求項18之配位體或如請求項20或21之融合蛋白，及 醤藥予上可接夂之稀釋劑、載劑、賦形劑或媒劑。 種核I其包含編碼如請求項1至17中任一項之變 體或如叫求項1 8之多特異性配位體、或如請求項2〇或 21之融合蛋白的核苷酸序列。 種核酉文其包含選自以下之〇〇M7h-11變體之核苦酸 146451.doc 201042039 序列：DOM7h-ll-3(SEQ ID NO: 5)、DOM7h-ll-15(SEQ ID NO: 2)、DOM7h-ll-12(SEQ ID NO: 1)、DOM7h-ll-18(SEQ ID NO: 3)及 DOM7h-ll-19(SEQ ID NO: 4)，或與 該所選序列至少80%—致之核苷酸序列。 25. —種核酸，其包含 DOM7h-ll-15sl2P(SEQ ID NO: 414)之 核苷酸序列或與該所選序列至少80% —致之核苷酸序 列。 26_ —種載體，其包含如請求項23、24或25之核酸。 ^ 27. —種經分離之宿主細胞，其包含如請求項26之載體。 28. —種如請求項1至17中任一項之變體、如請求項18之配 位體或如請求項20或21之融合蛋白的用途，其係用於製 造治療或預防患者之疾病或病症之藥物。 〇 146451.doc
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Families Citing this family (12)

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Publication number Priority date Publication date Assignee Title
SG174497A1 (en) * 2009-03-27 2011-10-28 Glaxo Group Ltd Drug fusions and conjugates
WO2011008814A2 (en) 2009-07-14 2011-01-20 Immune Tolerance Institute, Inc., A California Not-For-Profit Corporation Multiplexed measurement of exogenous and endogenous dna
US20120276098A1 (en) * 2009-09-30 2012-11-01 Bruce Hamilton Drug fusions and conjugates with extended half life
UA107200C2 (uk) * 2009-10-27 2014-12-10 Ґлаксо Ґруп Лімітед ОДИНИЧНИЙ ВАРІАБЕЛЬНИЙ ДОМЕН ІМУНОГЛОБУЛІНУ ПРОТИ РЕЦЕПТОРА ТИПУ 1 TNFα
CN103003303A (zh) * 2010-05-20 2013-03-27 葛兰素集团有限公司 改进的抗-血清白蛋白结合变体
WO2012020143A1 (en) * 2010-08-13 2012-02-16 Glaxo Group Limited Improved anti-serum albumin binding variants
CA2818621A1 (en) * 2010-11-24 2012-05-31 Glaxo Group Limited Multispecific antigen binding proteins targeting hgf
WO2012072731A2 (en) 2010-12-01 2012-06-07 Glaxo Group Limited Improved anti-serum albumin binding single variable domains
US20130310281A1 (en) 2011-02-02 2013-11-21 Glaxo Group Limited Novel antigen binding proteins
WO2017201340A2 (en) 2016-05-18 2017-11-23 Modernatx, Inc. Polynucleotides encoding relaxin
KR20200015505A (ko) 2017-06-05 2020-02-12 누맙 세러퓨틱스 아게 신규 항 hsa 항체
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Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL127127A0 (en) 1998-11-18 1999-09-22 Peptor Ltd Small functional units of antibody heavy chain variable regions
US20100081792A1 (en) * 2001-06-28 2010-04-01 Smithkline Beecham Corporation Ligand
US9321832B2 (en) 2002-06-28 2016-04-26 Domantis Limited Ligand
ES2263984T3 (es) 2002-06-28 2006-12-16 Domantis Limited Ligandos doble-especificos con una vida media serica aumentada.
US20060002935A1 (en) 2002-06-28 2006-01-05 Domantis Limited Tumor Necrosis Factor Receptor 1 antagonists and methods of use therefor
EP2172553A1 (en) 2004-03-24 2010-04-07 Domantis Limited Gas1 universal leader
MXPA06014031A (es) 2004-06-01 2007-10-08 Domantis Ltd Anticuerpos de fusion biespecificos con vida media de serica mejorada.
EP2769990A3 (en) 2004-12-02 2015-02-25 Domantis Limited Bispecific domain antibodies targeting serum albumin and GLP-1 or PYY
CA2632424A1 (en) * 2005-12-06 2007-06-14 Domantis Limited Bispecific ligands with binding specificity to cell surface targets and methods of use therefor
AU2007209201A1 (en) 2006-01-24 2007-08-02 Domantis Limited Fusion proteins that contain natural junctions
GB0621513D0 (en) 2006-10-30 2006-12-06 Domantis Ltd Novel polypeptides and uses thereof
CA2688433A1 (en) 2007-06-06 2008-12-11 Domantis Limited Methods for selecting protease resistant polypeptides
GB0724331D0 (en) 2007-12-13 2008-01-23 Domantis Ltd Compositions for pulmonary delivery
KR20110092328A (ko) 2008-11-26 2011-08-17 글락소 그룹 리미티드 Ｉｌ-13에 결합하는 리간드
US20110301335A1 (en) * 2009-02-19 2011-12-08 Stephen Duffield Anti-tnfr1 polypeptides, antibody variable domains & antagonists
PE20120170A1 (es) 2009-02-19 2012-03-21 Glaxo Group Ltd Variantes de union a anti-albumina de suero mejoradas
US20120107330A1 (en) * 2009-07-16 2012-05-03 Adriaan Allart Stoop Antagonists, uses & methods for partially inhibiting tnfr1
US20120276098A1 (en) * 2009-09-30 2012-11-01 Bruce Hamilton Drug fusions and conjugates with extended half life
CA2796932A1 (en) * 2010-04-21 2011-10-27 Glaxo Group Limited Binding domains

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