自身免疫抗體的制作方法
【專利摘要】本發(fā)明一般涉及與NSCLC有關(guān)的生物標(biāo)志物,及用于在人受試者中檢測和診斷非小細(xì)胞肺癌的方法和組合物。
【專利說明】自身免疫抗體 發(fā)明領(lǐng)域
[0001] 本發(fā)明提供用于鑒定會最多地受益于厄洛替尼(Erlotinib)治療的診斷有非小 細(xì)胞肺癌的患者的方法,其包括在所述患者的血清中檢測自身抗體。
[0002] 發(fā)明背景
[0003] Tarceva?是一種有口服活性的、有力的表皮生長因子受體(EGFR)酪氨酸激酶 (TKI)抑制劑。
[0004] 厄洛替尼鹽酸鹽是:Tarceva?中的活性組分,Tarceva?批準(zhǔn)作為單藥治療在化 療后用于晚期非小細(xì)胞肺癌(NSCLC)患者,作為維持治療用于化療期間無發(fā)展(一線維持) 或化療失敗后(二/三線維持)的患者。Tarceva?還批準(zhǔn)作為一線治療用于其腫瘤在EU 中包含EGFR激活性突變的患者。
[0005] 不尋常蛋白質(zhì)的表達(dá)在癌癥和病毒感染中是常見的。哺乳動物免疫系統(tǒng)含有一 個專門分支,其識別由細(xì)胞轉(zhuǎn)化誘導(dǎo)的蛋白質(zhì)(新抗原(neo-antigen)并有效消除表達(dá)這 些新抗原的細(xì)胞,發(fā)育期間沒有建立針對新抗原的耐受。認(rèn)為免疫系統(tǒng)的這個分支針對病 毒感染、由細(xì)胞分裂機(jī)制的錯誤引起的自發(fā)染色體和基因組重排、或致癌原誘導(dǎo)的轉(zhuǎn)化性 突變是有效的。雖然初始細(xì)胞毒性免疫應(yīng)答-其通過CD8+T細(xì)胞對MHCI復(fù)合物上展示的 不尋常蛋白質(zhì)的識別介導(dǎo)-快速且有效,針對病毒感染或異常細(xì)胞克隆的持續(xù)應(yīng)答需要 CD4+T輔助細(xì)胞的共刺激效應(yīng),CD4+T輔助細(xì)胞經(jīng)專門抗原呈遞細(xì)胞的MHCII復(fù)合物在呈遞 胞外肽(其可以源于在細(xì)胞毒性免疫應(yīng)答的第一階段中裂解的細(xì)胞)后激活。另外,這些 細(xì)胞能夠誘導(dǎo)持久的針對病毒或異常蛋白質(zhì)的B細(xì)胞應(yīng)答和抗體。已經(jīng)在結(jié)直腸癌中顯示 大量⑶8+T細(xì)胞浸潤腫瘤是比傳統(tǒng)腫瘤分期更好的預(yù)后標(biāo)志物(Koizumi,Hojo等2007 1), 而且已經(jīng)在幾乎所有主要實(shí)體癌中將它與有利的預(yù)后關(guān)聯(lián)起來,不管癌細(xì)胞類型。
[0006] 自身抗體是公知的,癌癥中的診斷性實(shí)體。許多癌癥自身抗體是正常情況下在胚 胎組織中表達(dá)的蛋白質(zhì),因此代表"外來"蛋白質(zhì),沒有建立針對它們的免疫耐受。癌癥史 晚期這些蛋白質(zhì)脫落到血流中引起體液免疫應(yīng)答。一個典型的例子是常見的癌癥標(biāo)志物 CEA(癌胚抗原)。腫瘤頻繁展現(xiàn)錯誤的蛋白質(zhì)加工。突出的例子包括受到細(xì)胞定位蛋白酶 不正確切割(存在針對P53N端序列的自身抗體是肺癌最特異性的生物標(biāo)志物之一,正常情 況下在該蛋白質(zhì)靶定至核后切割N端序列)或受到細(xì)胞糖基化酶不正確糖基化(針對不正 確〇-糖基化形式的MUCl的抗MUCl抗體是多種癌癥的生物標(biāo)志物)的蛋白質(zhì)。盡管在腫 瘤中頻繁觀察到P53突變,但是自身抗體針對這種蛋白質(zhì)的特異性幾乎總是針對該蛋白質(zhì) 的N端-更多地將p53的免疫原性與正常情況下短命且定位于核的蛋白質(zhì)的異位表達(dá)聯(lián) 系起來。
[0007] Li等2記載了 NSCLC患者的血清中天然EGFR自身抗體的檢測。Li等3和Chapman 等4記載了針對p53、HER2、NY-ES0-l、CAGE、MUCl和GBU4-5的天然自身抗體的檢測。而且, W020110739055涉及與癌癥疾病自較低的發(fā)展階段發(fā)展至較高的發(fā)展階段有關(guān)的腫瘤標(biāo)志 物。
[0008] 不尋常(突變的或以異常數(shù)量或定位表達(dá)的)腫瘤蛋白質(zhì)能引發(fā)抗體應(yīng)答。已 經(jīng)頻繁觀察到腫瘤誘導(dǎo)的自身抗體,而且已經(jīng)調(diào)查它們作為診斷標(biāo)志物的效用(Albert和 Darnell 20046)。雖然能找到具有卓越特異性的針對腫瘤蛋白質(zhì)的自身抗體,但是它們大 多數(shù)缺乏診斷測試需要的靈敏度。
[0009] 本領(lǐng)域知道少數(shù)可靠的預(yù)測厄洛替尼鹽酸鹽響應(yīng)的流行病學(xué)和遺傳標(biāo)志物。特別 地,記載了外顯子18-21 (受體的胞內(nèi)激酶域)中的EGFR突變與較好的預(yù)后以及與較好的 對TKI治療的響應(yīng)有聯(lián)系(Paz-Ares,Soulieres等2010 7)。當(dāng)前知道的唯一預(yù)測標(biāo)志物 (EGFR激活性突變)難以診斷,因?yàn)樾枰[瘤活檢。目前,只有約50 %的NSCLC患者是以 活檢診斷的(Reck,Hermes等20118)。明確需要更簡單的技術(shù)來檢測TKI功效的預(yù)測標(biāo)志 物。想要在診斷時鑒定響應(yīng)者,使得有盡可能多的患者盡可能早地受益于厄洛替尼治療,同 時為不太可能響應(yīng)的患者探索其它治療選項。
[0010] 發(fā)明詳述
[0011] 本發(fā)明解決的問題在于提供一種在人受試者中診斷癌癥的方法。
[0012] 本發(fā)明解決的問題在于提供一種在人受試者中診斷非小細(xì)胞肺癌的方法。
[0013] 本發(fā)明解決的問題在于提供一種在人受試者中診斷非小細(xì)胞肺癌的方法,其通過 提供針對突變型EGFR序列的抗體來進(jìn)行。
[0014] 通過本文所述方法鑒定的患者為會響應(yīng)厄洛替尼治療或其藥學(xué)可接受鹽,特別是 厄洛替尼鹽酸鹽的患者,特別是NSCLC患者。
[0015] 我們令人驚訝地發(fā)現(xiàn)本發(fā)明的自身抗體擁有診斷測試需要的靈敏度,尤其是針對 突變型EGFR序列的自身抗體。
[0016] EGFR正常情況下結(jié)合至細(xì)胞膜且不脫落入血流。EGFR是一種正常成體蛋白質(zhì),在 一些成體組織中已大量找到。預(yù)期會建立針對這種蛋白質(zhì)和它的許多變體的免疫耐受。幾 乎所有序列屬于分子的胞質(zhì)部分且專門抗原呈遞細(xì)胞看不到。突變僅僅影響EGFR分子的 一小部分。
[0017] 除非另有定義,本文中使用的所有術(shù)語具有與本發(fā)明所屬領(lǐng)域技術(shù)人員普遍理解 相同的含義。
[0018] 術(shù)語"代表健康群體人受試者的所述自身抗體的水平"指未罹患NSCLC的患者群 體的血清中自身抗體的均值水平的估值。
[0019] 術(shù)語"代表NSCLC患者的所述自身抗體的水平"指罹患NSCLC的患者群體的血清 中自身抗體的均值水平的估值。
[0020] 術(shù)語"總體存活(OS) "指自疾病診斷起,治療期間和之后患者存活的時間長度。正 如技術(shù)人員會領(lǐng)會的,如果患者屬于與另一個患者亞組相比具有統(tǒng)計學(xué)顯著更長的均值存 活時間的一個患者亞組,那么該患者的總體存活得到改善或增強(qiáng)。
[0021] 術(shù)語"無進(jìn)展存活(PFS) "指自疾病診斷起,治療期間和之后,根據(jù)主治醫(yī)師或調(diào)查 人員的評估,患者的疾病沒有變得更差,即沒有發(fā)展的時間長度。正如技術(shù)人員會領(lǐng)會的, 如果患者屬于與情況相似患者的對照組的平均或均值無進(jìn)展存活時間相比有更長的時間 疾病沒有發(fā)展的一個患者亞組,那么該患者的無進(jìn)展存活得到改善或增強(qiáng)。
[0022] 術(shù)語"患者"指想要治療的任何單一哺乳動物。特別地,"患者"為人受試者。更特 別地,患者為罹患癌癥,特別是NSCLC的人受試者。
[0023] 術(shù)語"自身抗體"為患者免疫系統(tǒng)針對一種或多種患者自身蛋白質(zhì)制造的一類蛋 白質(zhì)。
[0024] 術(shù)語"氨基酸"表示一組天然發(fā)生的羧基α-氨基酸,包括丙氨酸(三字母代碼: ala,單字母代碼:Α)、精氨酸(arg,R)、天冬酰胺(asn,Ν)、天冬氨酸(asp, D)、半胱氨酸 (cys,〇、谷氨酰胺(gln,Q)、谷氨酸(glu,E)、甘氨酸(gly,G)、組氨酸(his,H)、異亮氨 酸(ile,I)、亮氨酸(leu,L)、賴氨酸(lys,K)、甲硫氨酸(met, M)、苯丙氨酸(phe,F(xiàn))、脯氨 酸(pro, P)、絲氨酸(ser,S)、蘇氨酸(thr,T)、色氨酸(trp,W)、酪氨酸(tyr,Y)、和纟顏氨酸 (val, V)。
[0025] 如本文中使用的,"療法"或"治療"(及其語法變型)指試圖改變所治療個體中疾 病的自然過程的臨床干預(yù),而且可以為了預(yù)防或在臨床病理過程期間實(shí)施。想要的治療效 果包括但不限于預(yù)防疾病發(fā)生或再發(fā)生、緩解癥狀、削弱疾病的任何直接或間接病理后果、 預(yù)防轉(zhuǎn)移、降低疾病發(fā)展速率、改善或減輕疾病狀態(tài)、和消除或改善預(yù)后。
[0026] 如本文中使用的,術(shù)語"基因"包括基因的變體。術(shù)語"變體"涉及與通過GenBank 登錄號給出的核酸序列實(shí)質(zhì)性相似的核酸序列。本領(lǐng)域技術(shù)人員能較好地理解術(shù)語"實(shí)質(zhì) 性相似"。特別地,基因變體可以是與人群中最流行的等位基因的核酸序列相比顯示核苷酸 交換的等位基因。優(yōu)選地,此類實(shí)質(zhì)性相似核酸序列與最流行的等位基因具有至少80 %,優(yōu) 選至少85 %,更優(yōu)選至少90 %,最優(yōu)選至少95 %的序列相似性。術(shù)語"變體"還意圖涉及剪 接變體。
[0027] 術(shù)語"突變"指基因組序列中的變化。這些隨機(jī)序列可以定義為細(xì)胞中的突發(fā)和 自發(fā)變化。突變可導(dǎo)致序列中數(shù)種不同類型的變化;這些可以沒有影響,改變基因的產(chǎn)物, 或阻止基因正確或完全發(fā)揮功能。術(shù)語"體細(xì)胞突變"指遺傳結(jié)構(gòu)中既不是繼承得到的也 不會傳給后代的變化。
[0028] 如本文中使用的,短語"推薦治療"指使用所生成的涉及患者的樣品中生物標(biāo)志物 或自身抗體的水平或存在的信息或數(shù)據(jù)來鑒定患者為適合或不適合用某種療法治療。在一 些實(shí)施方案中,所述療法可包含藥物。所述信息或數(shù)據(jù)可以是任何形式,書面的、口頭的或 電子的。在一些實(shí)施方案中,使用所生成的信息或數(shù)據(jù)包括傳達(dá)、呈現(xiàn)、報告、存儲、發(fā)送、轉(zhuǎn) 移、供應(yīng)、傳輸、遞送、分發(fā)、或其組合。在一些實(shí)施方案中,傳達(dá)、呈現(xiàn)、報告、存儲、發(fā)送、轉(zhuǎn) 移、供應(yīng)、傳輸、遞送、分發(fā)、或其組合是由計算裝置、分析單元或其組合實(shí)施的。在一些進(jìn)一 步的實(shí)施方案中,傳達(dá)、呈現(xiàn)、報告、存儲、發(fā)送、轉(zhuǎn)移、供應(yīng)、傳輸、遞送、分發(fā)、或其組合是由 實(shí)驗(yàn)室或醫(yī)學(xué)專業(yè)人員實(shí)施的。在一些實(shí)施方案中,所述信息或數(shù)據(jù)包括所述生物標(biāo)志物 或自身抗體的水平與參照水平的比較。在一些實(shí)施方案中,所述信息或數(shù)據(jù)包括樣品中存 在或缺失所述生物標(biāo)志物或自身抗體的指示。在一些實(shí)施方案中,所述信息或數(shù)據(jù)包括患 者適合或不適合用包含所述藥物的療法治療的指示。在一些實(shí)施方案中,所述療法為厄洛 替尼。
[0029] 如本文中使用的,短語"提供診斷"指使用所生成的涉及患者的樣品中生物標(biāo)志物 或自身抗體的水平或存在的信息或數(shù)據(jù)來診斷患者中的疾病。所述信息或數(shù)據(jù)可以是任何 形式,書面的、口頭的或電子的。在一些實(shí)施方案中,使用所生成的信息或數(shù)據(jù)包括呈現(xiàn)、報 告、存儲、發(fā)送、轉(zhuǎn)移、供應(yīng)、傳輸、遞送、分發(fā)、或其組合。在一些實(shí)施方案中,呈現(xiàn)、報告、存 儲、發(fā)送、轉(zhuǎn)移、供應(yīng)、傳輸、遞送、分發(fā)、或其組合是由計算裝置、分析單元或其組合實(shí)施的。 在一些實(shí)施方案中,呈現(xiàn)、報告、存儲、發(fā)送、轉(zhuǎn)移、供應(yīng)、傳輸、遞送、分發(fā)、或其組合是由實(shí) 驗(yàn)室或醫(yī)學(xué)專業(yè)人員實(shí)施的。在一些實(shí)施方案中,所述信息或數(shù)據(jù)包括所述生物標(biāo)志物或 自身抗體的水平與參照水平的比較。在一些實(shí)施方案中,所述信息或數(shù)據(jù)包括樣品中存在 或缺失所述生物標(biāo)志物或自身抗體的指示。在一些實(shí)施方案中,所述信息或數(shù)據(jù)包括患者 診斷有所述疾病的指示。在一些實(shí)施方案中,所述疾病為非小細(xì)胞肺癌。
[0030] 在TASK研究期間,收集了活檢材料并對腫瘤細(xì)胞測試了最頻繁的體細(xì)胞突變的 存在情況,即外顯子19刪除和外顯子21點(diǎn)突變。在TASK研究期間,在多個時間點(diǎn)(給藥 前、第8天、第22天和發(fā)展)自所有患者收集了血清樣品并評估了針對EGFR的自身抗體。
[0031] 在這些患者中,預(yù)測疹發(fā)生或無進(jìn)展或總體存活延長的自身抗原性肽序列必然包 括一套自EGFR序列衍生,始于第737位且延伸通過第756位的序列。這些肽包括一些序列 變體,但是必然包括具有第746-750位或附近處的刪除的序列(表2)。
[0032] 這恰好對應(yīng)于外顯子19體細(xì)胞突變中的刪除的位置,已知其預(yù)示源于TKI治療的 突出功效(Rosell 等 20099, Mok 等 20091°)。
[0033] 腫瘤組織中外顯子19中存在體細(xì)胞EGFR突變產(chǎn)生蛋白質(zhì)變體,免疫系統(tǒng)未針對 它形成耐受。該體細(xì)胞突變僅僅發(fā)生在腫瘤中,因此,如果它誘導(dǎo)自身抗體,在患者的血清 中能檢測到的話,它可用于得出關(guān)于NSCLC組織中存在外顯子19突變或外顯子21突變 的結(jié)論,公知它預(yù)測無進(jìn)展存活延長和酪氨酸激酶單一療法優(yōu)于化療(Heigener和Reck 201111)。
[0034] 可使用來自患者的標(biāo)準(zhǔn)血液樣品檢測自身抗體,無需以活檢獲得腫瘤細(xì)胞。這相 對于當(dāng)前實(shí)踐是一個較大優(yōu)點(diǎn),因?yàn)橛杏媚[瘤樣品的回收率甚至在臨床研究中也不超過 50% (Reck,Hermes 等 201112)。
[0035] 能檢測出抗EGFR自身抗體在NSCLC患者的血液樣品中的濃度比健康對照中高 (圖1)。特別地,已經(jīng)鑒定出肽序列,產(chǎn)生具有高免疫原性的連續(xù)區(qū)域,在患者和健康對照 血清之間具有較大差異。鑒定了連續(xù)序列段,其中超過30%的癌癥患者中各種肽信號對對 照中的最大值的比大于8(表1)。
[0036]
【權(quán)利要求】
1. 一種在人受試者中診斷非小細(xì)胞肺癌的方法,其包括: 在該人受試者的血液樣品中測量選自識別突變型人EGFR的自身抗體組的自身抗體的 水平,其中該人受試者的血液樣品中所述選自識別突變型人EGFR的自身抗體組的自身抗 體的水平與代表健康群體人受試者的所述自身抗體的水平相比升高指示非小細(xì)胞肺癌。
2. 依照權(quán)利要求1的方法,其中所述自身抗體識別選自下組的突變型EGFR肽: Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559,和 Seq. Id. No. 560。
3. 依照權(quán)利要求1-2任一項的方法,其中所述自身抗體識別選自下組的突變型EGFR 肽: Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15,Seq. Id. No. 16,Seq. Id. No. 17,Seq. Id. No. 18,Seq. Id. No. 19,Seq. Id. No. 20,Seq. Id. No. 21,Seq. Id. No. 22,Seq. Id. No. 23,Seq. Id. No. 24,Seq. Id. No. 25,Seq. Id. No. 26,Seq. Id. No. 27,Seq. Id. No. 28,Seq. Id. No. 29,Seq. Id. No. 30,Seq. Id. No. 31, Seq. Id. No. 32,Seq. Id. No. 33,Seq. Id. No. 34,Seq. Id. No. 35,Seq. Id. No. 36,Seq. Id. No. 37,Seq. Id. No. 38,Seq. Id. No. 39,Seq. Id. No. 40,Seq. Id. No. 41,Seq. Id. No. 42,Seq. Id. No. 43,Seq. Id. No. 44,Seq. Id. No. 45,Seq. Id. No. 46,Seq. Id. No. 47,Seq. Id. No. 48, Seq. Id. No. 49,Seq. Id. No. 50,Seq. Id. No. 51,Seq. Id. No. 52,Seq. Id. No. 53,Seq. Id. No. 54,Seq. Id. No. 55,Seq. Id. No. 56,Seq. Id. No. 57,Seq. Id. No. 58,Seq. Id. No. 59,Seq. Id. No. 60,Seq. Id. No. 61,Seq. Id. No. 62,Seq. Id. No. 63,Seq. Id. No. 65,Seq. Id. No. 66, Seq. Id. No. 67,Seq. Id. No. 68,Seq. Id. No. 69,Seq. Id. No. 70,Seq. Id. No. 71,Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78,Seq. Id. No. 79,Seq. Id. No. 80,Seq. Id. No. 81,Seq. Id. No. 82,Seq. Id. No. 83, Seq. Id. No. 84,Seq. Id. No. 85,Seq. Id. No. 86,Seq. Id. No. 87,Seq. Id. No. 88,Seq. Id. No. 89,Seq. Id. No. 90,Seq. Id. No. 91,Seq. Id. No. 92,Seq. Id. No. 93,Seq. Id. No. 94,Seq. Id. No. 95,Seq. Id. No. 96,Seq. Id. No. 97,Seq. Id. No. 98,Seq. Id. No. 99,Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. Ill, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171,Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203,Seq. Id. No. 204,Seq. Id. No. 205,Seq. Id. No. 206,Seq. Id. No. 207,Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223,Seq. Id. No. 224,Seq. Id. No. 225,Seq. Id. No. 226,Seq. Id. No. 227,Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233,Seq. Id. No. 234,Seq. Id. No. 235,Seq. Id. No. 236,Seq. Id. No. 237,Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253,Seq. Id. No. 254,Seq. Id. No. 255,Seq. Id. No. 256,Seq. Id. No. 257,Seq. Id. No. 258,Seq. Id. No. 259,Seq. Id. No. 260,Seq. Id. No. 261,Seq. Id. No. 262,Seq. Id. No. 263,Seq. Id. No. 264,Seq. Id. No. 265,Seq. Id. No. 266,Seq. Id. No. 267,Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283,Seq. Id. No. 284,Seq. Id. No. 285,Seq. Id. No. 286,Seq. Id. No. 287,Seq. Id. No. 288,Seq. Id. No. 289,Seq. Id. No. 290,Seq. Id. No. 291,Seq. Id. No. 292,Seq. Id. No. 293,Seq. Id. No. 294,Seq. Id. No. 295,Seq. Id. No. 296,Seq. Id. No. 297,Seq. Id. No. 298,Seq. Id. No. 299,Seq. Id. No. 300,Seq. Id. No. 301,Seq. Id. No. 302,Seq. Id. No. 303,Seq. Id. No. 304,Seq. Id. No. 305,Seq. Id. No. 306,Seq. Id. No. 307,Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324,Seq. Id. No. 325,Seq. Id. No. 326,Seq. Id. No. 327,Seq. Id. No. 328,Seq. Id. No. 329,Seq. Id. No. 330,Seq. Id. No. 331,Seq. Id. No. 332,Seq. Id. No. 333,Seq. Id. No. 334,Seq. Id. No. 335,Seq. Id. No. 336,Seq. Id. No. 337,Seq. Id. No. 338,Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349,Seq. Id. No. 350,Seq. Id. No. 351,Seq. Id. No. 352,Seq. Id. No. 353,Seq. Id. No. 354,Seq. Id. No. 355,Seq. Id. No. 356,Seq. Id. No. 357,Seq. Id. No. 358,Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364,Seq. Id. No. 365,Seq. Id. No. 366,Seq. Id. No. 367,Seq. Id. No. 368,Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579,Seq. Id. No. 580,Seq. Id. No. 581,Seq. Id. No. 582,Seq. Id. No. 583,Seq. Id. No. 584,Seq. Id. No. 585,Seq. Id. No. 586,Seq. Id. No. 587,Seq. Id. No. 588,Seq. Id. No. 589,Seq. Id. No. 590,Seq. Id. No. 591,Seq. Id. No. 592,Seq. Id. No. 593,Seq. Id. No. 594,Seq. Id. No. 595,Seq. Id. No. 596,Seq. Id. No. 597,Seq. Id. No. 598,Seq. Id. No. 599,Seq. Id. No. 601,Seq. Id. No. 604,Seq. Id. No. 605,Seq. Id. No. 606,Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 和 Seq. Id. No. 619。
4. 依照權(quán)利要求1-3任一項的方法,其中所述自身抗體識別選自下組的突變型EGFR 肽:Seq. Id. No. 1,Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 和 Seq. Id. No. 15。
5. 依照權(quán)利要求1-3任一項的方法,其中所述自身抗體識別選自下組的突變型EGFR 肽: Seq. Id. No. 16,Seq. Id. No. 17,Seq. Id. No. 18,Seq. Id. No. 19,Seq. Id. No. 20,Seq. Id. No. 21,Seq. Id. No. 22,Seq. Id. No. 23,Seq. Id. No. 24,Seq. Id. No. 25,Seq. Id. No. 26, Seq. Id. No. 27,Seq. Id. No. 28,Seq. Id. No. 29,Seq. Id. No. 30,Seq. Id. No. 31,Seq. Id. No. 32,Seq. Id. No. 33,Seq. Id. No. 34,Seq. Id. No. 35,Seq. Id. No. 36,Seq. Id. No. 37, Seq. Id. No. 38,Seq. Id. No. 39,Seq. Id. No. 40,Seq. Id. No. 41,Seq. Id. No. 42,Seq. Id. No. 43,Seq. Id. No. 44,Seq. Id. No. 45,Seq. Id. No. 46,Seq. Id. No. 47,Seq. Id. No. 48, Seq. Id. No. 49,Seq. Id. No. 50,Seq. Id. No. 51,Seq. Id. No. 52,Seq. Id. No. 53,Seq. Id. No. 54,Seq. Id. No. 55,Seq. Id. No. 56,Seq. Id. No. 57,Seq. Id. No. 58,Seq. Id. No. 59, Seq. Id. No. 60,Seq. Id. No. 61,Seq. Id. No. 62,Seq. Id. No. 63,Seq. Id. No. 65,Seq. Id. No. 66,Seq. Id. No. 67,Seq. Id. No. 68,Seq. Id. No. 69,Seq. Id. No. 70,Seq. Id. No. 71, Seq. Id. No. 72,Seq. Id. No. 73,Seq. Id. No. 74,Seq. Id. No. 75,Seq. Id. No. 76,Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81,Seq. Id. No. 82, Seq. Id. No. 83,Seq. Id. No. 84,Seq. Id. No. 85,Seq. Id. No. 86,Seq. Id. No. 87,Seq. Id. No. 88,Seq. Id. No. 89,Seq. Id. No. 90,Seq. Id. No. 91,Seq. Id. No. 92,Seq. Id. No. 93, Seq. Id. No. 94,Seq. Id. No. 95,Seq. Id. No. 96,Seq. Id. No. 97,Seq. Id. No. 98,Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. Ill, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200,Seq. Id. No. 201,Seq. Id. No. 202,Seq. Id. No. 203,Seq. Id. No. 204,Seq. Id. No. 205,Seq. Id. No. 206,Seq. Id. No. 207,Seq. Id. No. 208,Seq. Id. No. 209,Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220,Seq. Id. No. 221,Seq. Id. No. 222,Seq. Id. No. 223,Seq. Id. No. 224,Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230,Seq. Id. No. 231,Seq. Id. No. 232,Seq. Id. No. 233,Seq. Id. No. 234,Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250,Seq. Id. No. 251,Seq. Id. No. 252,Seq. Id. No. 253,Seq. Id. No. 254,Seq. Id. No. 255,Seq. Id. No. 256,Seq. Id. No. 257,Seq. Id. No. 258,Seq. Id. No. 259,Seq. Id. No. 260,Seq. Id. No. 261,Seq. Id. No. 262,Seq. Id. No. 263,Seq. Id. No. 264,Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280,Seq. Id. No. 281,Seq. Id. No. 282,Seq. Id. No. 283,Seq. Id. No. 284,Seq. Id. No. 285,Seq. Id. No. 286,Seq. Id. No. 287,Seq. Id. No. 288,Seq. Id. No. 289,Seq. Id. No. 290,Seq. Id. No. 291,Seq. Id. No. 292,Seq. Id. No. 293,Seq. Id. No. 294,Seq. Id. No. 295,Seq. Id. No. 296,Seq. Id. No. 297,Seq. Id. No. 298,Seq. Id. No. 299,Seq. Id. No. 300,Seq. Id. No. 301,Seq. Id. No. 302,Seq. Id. No. 303,Seq. Id. No. 304,Seq. Id. No. 305,Seq. Id. No. 306,Seq. Id. No. 307,Seq. Id. No. 308,Seq. Id. No. 310,Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321,Seq. Id. No. 322,Seq. Id. No. 323,Seq. Id. No. 324,Seq. Id. No. 325,Seq. Id. No. 326,Seq. Id. No. 327,Seq. Id. No. 328,Seq. Id. No. 329,Seq. Id. No. 330,Seq. Id. No. 331,Seq. Id. No. 332,Seq. Id. No. 333,Seq. Id. No. 334,Seq. Id. No. 335,Seq. Id. No. 336,Seq. Id. No. 337,Seq. Id. No. 338,Seq. Id. No. 339,Seq. Id. No. 340,Seq. Id. No. 341,Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Scq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 和 Seq. Id. No. 517。
6.依照權(quán)利要求1-3任一項的方法,其中所述自身抗體識別選自下組的突變型EGFR 肽: Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527,Seq. Id. No. 528,Seq. Id. No. 529,Seq. Id. No. 530,Seq. Id. No. 531,Seq. Id. No. 532,Seq. Id. No. 533,Seq. Id. No. 534,Seq. Id. No. 535,Seq. Id. No. 536,Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552,Seq. Id. No. 553,Seq. Id. No. 554,Seq. Id. No. 555,Seq. Id. No. 557,Seq. Id. No. 559,Seq. Id. No. 560,Seq. Id. No. 562,Seq. Id. No. 563,Seq. Id. No. 564,Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581,Seq. Id. No. 582,Seq. Id. No. 583,Seq. Id. No. 584,Seq. Id. No. 585,Seq. Id. No. 586,Seq. Id. No. 587,Seq. Id. No. 588,Seq. Id. No. 589,Seq. Id. No. 590,Seq. Id. No. 591,Seq. Id. No. 592,Seq. Id. No. 593,Seq. Id. No. 594,Seq. Id. No. 595,Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 和 Seq. Id. No. 601。
7. 依照權(quán)利要求1-3任一項的方法,其中所述自身抗體識別選自下組的突變型EGFR 肽:Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 和 Seq. Id. No. 619。
8. 依照權(quán)利要求1-7任一項的方法,其中該人受試者的血液樣品中自身抗體的水平比 代表健康群體人受試者的所述自身抗體的水平高5倍。
9. 厄洛替尼(Erlotinib)或其藥學(xué)可接受鹽,特別是厄洛替尼鹽酸鹽,其用于治療通 過權(quán)利要求1至8任一項的方法鑒定的NSCLC患者,包括對該患者施用厄洛替尼或其藥學(xué) 可接受鹽,特別是厄洛替尼鹽酸鹽。
10. 自身抗體用于預(yù)測NSCLC患者對厄洛替尼或其藥學(xué)可接受鹽,特別是厄洛替尼鹽 酸鹽,治療的響應(yīng)的用途,該抗體是通過權(quán)利要求1至8任一項的方法鑒定的。
11. 一種用于在人受試者的血液樣品中檢測一種或多種選自識別突變型人EGFR的自 身抗體組的自身抗體的水平的試劑盒,其中該人受試者的血液樣品中所述選自識別突變型 人EGFR的自身抗體組的自身抗體的水平與代表健康群體人受試者的所述自身抗體的水平 相比升高指示非小細(xì)胞肺癌。
12. 依照權(quán)利要求11的試劑盒,其中所述自身抗體識別選自下組的突變型EGFR肽: Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559,和 Seq. Id. No. 560。
13. 依照權(quán)利要求11的試劑盒,其中所述自身抗體識別選自下組的突變型EGFR肽: Seq. Id. No. 1,Seq. Id. No. 2,Seq. Id. No. 4,Seq. Id. No. 5,Seq. Id. No. 6,Seq. Id. No. 7 和 Seq. Id. No. 15。
14. 依照權(quán)利要求11的試劑盒,其中所述自身抗體識別選自下組的突變型EGFR肽: Seq. Id. No. 16, Seq. Id. No. 17, Seq. Id. No. 18, Seq. Id. No. 19, Seq. Id. No. 20, Seq. Id. No. 21, Seq. Id. No. 22, Seq. Id. No. 23, Seq. Id. No. 24, Seq. Id. No. 25, Seq. Id. No. 26, Seq. Id. No. 27, Seq. Id. No. 28, Seq. Id. No. 29, Seq. Id. No. 30, Seq. Id. No. 31, Seq. Id. No. 32, Seq. Id. No. 33, Seq. Id. No. 34, Seq. Id. No. 35, Seq. Id. No. 36, Seq. Id. No. 37, Seq. Id. No. 38, Seq. Id. No. 39, Seq. Id. No. 40, Seq. Id. No. 41, Seq. Id. No. 42, Seq. Id. No. 43, Seq. Id. No. 44, Seq. Id. No. 45, Seq. Id. No. 46, Seq. Id. No. 47, Seq. Id. No. 48, Seq. Id. No. 49, Seq. Id. No. 50, Seq. Id. No. 51, Seq. Id. No. 52, Seq. Id. No. 53, Seq. Id. No. 54, Seq. Id. No. 55, Seq. Id. No. 56, Seq. Id. No. 57, Seq. Id. No. 58, Seq. Id. No. 59, Seq. Id. No. 60, Seq. Id. No. 61, Seq. Id. No. 62, Seq. Id. No. 63, Seq. Id. No. 65, Seq. Id. No. 66, Seq. Id. No. 67, Seq. Id. No. 68, Seq. Id. No. 69, Seq. Id. No. 70, Seq. Id. No. 71, Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81, Seq. Id. No. 82, Seq. Id. No. 83, Seq. Id. No. 84, Seq. Id. No. 85, Seq. Id. No. 86, Seq. Id. No. 87, Seq. Id. No. 88, Seq. Id. No. 89, Seq. Id. No. 90, Seq. Id. No. 91, Seq. Id. No. 92, Seq. Id. No. 93, Seq. Id. No. 94, Seq. Id. No. 95, Seq. Id. No. 96, Seq. Id. No. 97, Seq. Id. No. 98, Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. Ill, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250,Seq. Id. No. 251,Seq. Id. No. 252,Seq. Id. No. 253,Seq. Id. No. 254,Seq. Id. No. 255,Seq. Id. No. 256,Seq. Id. No. 257,Seq. Id. No. 258,Seq. Id. No. 259,Seq. Id. No. 260,Seq. Id. No. 261,Seq. Id. No. 262,Seq. Id. No. 263,Seq. Id. No. 264,Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280,Seq. Id. No. 281,Seq. Id. No. 282,Seq. Id. No. 283,Seq. Id. No. 284,Seq. Id. No. 285,Seq. Id. No. 286,Seq. Id. No. 287,Seq. Id. No. 288,Seq. Id. No. 289,Seq. Id. No. 290,Seq. Id. No. 291,Seq. Id. No. 292,Seq. Id. No. 293,Seq. Id. No. 294,Seq. Id. No. 295,Seq. Id. No. 296,Seq. Id. No. 297,Seq. Id. No. 298,Seq. Id. No. 299,Seq. Id. No. 300,Seq. Id. No. 301,Seq. Id. No. 302,Seq. Id. No. 303,Seq. Id. No. 304,Seq. Id. No. 305,Seq. Id. No. 306,Seq. Id. No. 307,Seq. Id. No. 308,Seq. Id. No. 310,Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321,Seq. Id. No. 322,Seq. Id. No. 323,Seq. Id. No. 324,Seq. Id. No. 325,Seq. Id. No. 326,Seq. Id. No. 327,Seq. Id. No. 328,Seq. Id. No. 329,Seq. Id. No. 330,Seq. Id. No. 331,Seq. Id. No. 332,Seq. Id. No. 333,Seq. Id. No. 334,Seq. Id. No. 335,Seq. Id. No. 336,Seq. Id. No. 337,Seq. Id. No. 338,Seq. Id. No. 339,Seq. Id. No. 340,Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351,Seq. Id. No. 352,Seq. Id. No. 353,Seq. Id. No. 354,Seq. Id. No. 355,Seq. Id. No. 356,Seq. Id. No. 357,Seq. Id. No. 358,Seq. Id. No. 359,Seq. Id. No. 360,Seq. Id. No. 361,Seq. Id. No. 362,Seq. Id. No. 363,Seq. Id. No. 364,Seq. Id. No. 365,Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383,Seq. Id. No. 384,Seq. Id. No. 385,Seq. Id. No. 386,Seq. Id. No. 387,Seq. Id. No. 388,Seq. Id. No. 389,Seq. Id. No. 390,Seq. Id. No. 391,Seq. Id. No. 392,Seq. Id. No. 393,Seq. Id. No. 394,Seq. Id. No. 395,Seq. Id. No. 396,Seq. Id. No. 397,Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 和 Seq. Id. No. 517。
15. 依照權(quán)利要求11的試劑盒,其中所述自身抗體識別選自下組的突變型EGFR肽: Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527,Seq. Id. No. 528,Seq. Id. No. 529,Seq. Id. No. 530,Seq. Id. No. 531,Seq. Id. No. 532,Seq. Id. No. 533,Seq. Id. No. 534,Seq. Id. No. 535,Seq. Id. No. 536,Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552,Seq. Id. No. 553,Seq. Id. No. 554,Seq. Id. No. 555,Seq. Id. No. 557,Seq. Id. No. 559,Seq. Id. No. 560,Seq. Id. No. 562,Seq. Id. No. 563,Seq. Id. No. 564,Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581,Seq. Id. No. 582,Seq. Id. No. 583,Seq. Id. No. 584,Seq. Id. No. 585,Seq. Id. No. 586,Seq. Id. No. 587,Seq. Id. No. 588,Seq. Id. No. 589,Seq. Id. No. 590,Seq. Id. No. 591,Seq. Id. No. 592,Seq. Id. No. 593,Seq. Id. No. 594,Seq. Id. No. 595,Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 和 Seq. Id. No. 601。
16. 依照權(quán)利要求11的試劑盒,其中所述自身抗體識別選自下組的突變型EGFR 肽:Seq. Id. No. 604, Seq. Id. No. 605, Seq. Id. No. 606, Seq. Id. No. 607, Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 和 Seq. Id. No. 619。
17. -種在人受試者中診斷非小細(xì)胞肺癌的方法,其包括: 在該人受試者的血液樣品中測量選自識別人EGFR的自身抗體組的自身抗體的水平, 其中該人受試者的血液樣品中所述選自識別人EGFR的自身抗體組的自身抗體的水平與代 表健康群體人受試者的所述自身抗體的水平相比升高指示非小細(xì)胞肺癌。
18. 依照權(quán)利要求16的方法,其中所述自身抗體識別選自下組的突變型EGFR肽:Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521 和 Seq. Id. No. 561。
19. 依照權(quán)利要求17-18任一項的方法,其中所述自身抗體識別選自下組的EGFR肽: Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 3, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7,Seq. Id. No. 8,Seq. Id. No. 9,Seq. Id. No. 10,Seq. Id. No. 11,Seq. Id. No. 12, Seq. Id. No. 13,Seq. Id. No. 14,Seq. Id. No. 15,Seq. Id. No. 16,Seq. Id. No. 17,Seq. Id. No. 18,Seq. Id. No. 19,Seq. Id. No. 20,Seq. Id. No. 21,Seq. Id. No. 22,Seq. Id. No. 23,Seq. Id. No. 24,Seq. Id. No. 25,Seq. Id. No. 26,Seq. Id. No. 27,Seq. Id. No. 28,Seq. Id. No. 29, Seq. Id. No. 30,Seq. Id. No. 31,Seq. Id. No. 32,Seq. Id. No. 33,Seq. Id. No. 34,Seq. Id. No. 35,Seq. Id. No. 36,Seq. Id. No. 37,Seq. Id. No. 38,Seq. Id. No. 39,Seq. Id. No. 40,Seq. Id. No. 41,Seq. Id. No. 42,Seq. Id. No. 43,Seq. Id. No. 44,Seq. Id. No. 45,Seq. Id. No. 46, Seq. Id. No. 47,Seq. Id. No. 48,Seq. Id. No. 49,Seq. Id. No. 50,Seq. Id. No. 51,Seq. Id. No. 52,Seq. Id. No. 53,Seq. Id. No. 54,Seq. Id. No. 55,Seq. Id. No. 56,Seq. Id. No. 57,Seq. Id. No. 58,Seq. Id. No. 59,Seq. Id. No. 60,Seq. Id. No. 61,Seq. Id. No. 62,Seq. Id. No. 63, Seq. Id. No. 64,Seq. Id. No. 65,Seq. Id. No. 66,Seq. Id. No. 67,Seq. Id. No. 68,Seq. Id. No. 69,Seq. Id. No. 70,Seq. Id. No. 71,Seq. Id. No. 72,Seq. Id. No. 73,Seq. Id. No. 74,Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81,Seq. Id. No. 82,Seq. Id. No. 83,Seq. Id. No. 84,Seq. Id. No. 85,Seq. Id. No. 86,Seq. Id. No. 87,Seq. Id. No. 88,Seq. Id. No. 89,Seq. Id. No. 90,Seq. Id. No. 91,Seq. Id. No. 92,Seq. Id. No. 93,Seq. Id. No. 94,Seq. Id. No. 95,Seq. Id. No. 96,Seq. Id. No. 97, Seq. Id. No. 98,Seq. Id. No. 99,Seq. Id. No. 100,Seq. Id. No. 101,Seq. Id. No. 102,Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. Ill, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 309, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 370, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 373, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 525, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 561, Seq. Id. No. 562, Seq. Id. No. 563, Seq. Id. No. 564, Seq. Id. No. 565, Seq. Id. No. 566, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583,Seq. Id. No. 584,Seq. Id. No. 585,Seq. Id. No. 586,Seq. Id. No. 587,Seq. Id. No. 588,Seq. Id. No. 589,Seq. Id. No. 590,Seq. Id. No. 591,Seq. Id. No. 592,Seq. Id. No. 593,Seq. Id. No. 594,Seq. Id. No. 595,Seq. Id. No. 596,Seq. Id. No. 597,Seq. Id. No. 598,Seq. Id. No. 599,Seq. Id. No. 600,Seq. Id. No. 601,Seq. Id. No. 602,Seq. Id. No. 603,Seq. Id. No. 604,Seq. Id. No. 605,Seq. Id. No. 606,Seq. Id. No. 607,Seq. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618,和 Seq. Id. No. 619。
20. 依照權(quán)利要求19任一項的方法,其中所述自身抗體識別選自下組的EGFR肽:Seq. Id. No. 3,Seq. Id. No. 8,Seq. Id. No. 9,Seq. Id. No. 10,Seq. Id. No. 11,Seq. Id. No. 12,Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373,Seq. Id. No. 519,Seq. Id. No. 520,Seq. Id. No. 521,Seq. Id. No. 525,Seq. Id. No. 556,Seq. Id. No. 558,Seq. Id. No. 561,Seq. Id. No. 566,Seq. Id. No. 600,Seq. Id. No. 602 和 Seq. Id. No. 603。
21. 依照權(quán)利要求17-20任一項的方法,其中該人受試者的血液樣品中自身抗體的水 平比代表健康群體人受試者的所述自身抗體的水平高5倍。
22. 厄洛替尼或其藥學(xué)可接受鹽,特別是厄洛替尼鹽酸鹽,其用于治療通過權(quán)利要求 17至21任一項的方法鑒定的NSCLC患者,包括對該患者施用厄洛替尼或其藥學(xué)可接受鹽, 特別是厄洛替尼鹽酸鹽。
23. 自身抗體用于預(yù)測NSCLC患者對厄洛替尼或其藥學(xué)可接受鹽,特別是厄洛替尼鹽 酸鹽,治療的響應(yīng)的用途,該抗體是通過權(quán)利要求17至21任一項的方法鑒定的。
24. -種用于在人受試者的血液樣品中檢測一種或多種選自識別人EGFR的自身抗體 組的自身抗體的水平的試劑盒,其中該人受試者的血液樣品中所述選自識別人EGFR的自 身抗體組的自身抗體的水平與代表健康群體人受試者的所述自身抗體的水平相比升高指 示非小細(xì)胞肺癌。
25. 依照權(quán)利要求24的試劑盒,其中所述自身抗體識別選自下組的EGFR肽:Seq. Id. No. 3,Seq. Id. No. 8,Seq. Id. No. 9,Seq. Id. No. 10,Seq. Id. No. 11,Seq. Id. No. 12,Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373,Seq. Id. No. 519,Seq. Id. No. 520,Seq. Id. No. 521,Seq. Id. No. 525,Seq. Id. No. 556,Seq. Id. No. 558,Seq. Id. No. 561,Seq. Id. No. 566,Seq. Id. No. 600,Seq. Id. No. 602 和 Seq. Id. No. 603。
26. 依照權(quán)利要求25的試劑盒,其中所述自身抗體識別選自下組的EGFR肽:Seq. Id. No. 519, Seq. Id. No. 520, Seq. Id. No. 521,和 Seq. Id. No. 561。
27. -種在人受試者中診斷非小細(xì)胞肺癌的方法,其包括: a) 在該人受試者的血液樣品中測量選自識別突變型人EGFR的自身抗體組的自身抗體 的水平, b) 比較所述自身抗體的水平與參照水平,并 C)當(dāng)所述自身抗體的水平超出參照水平時提供非小細(xì)胞肺癌的診斷。
28. -種在人受試者中診斷非小細(xì)胞肺癌的方法,其包括: a) 在該人受試者的血液樣品中測量選自識別突變型人EGFR的自身抗體組的自身抗體 的水平, b) 比較所述自身抗體的水平與參照水平,并 c) 當(dāng)所述自身抗體的水平超出參照水平時推薦治療。
29. 依照權(quán)利要求27或28的方法,其中所述自身抗體識別選自下組的突變型EGFR肽: Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 556, Seq. Id. No. 557, Seq. Id. No. 558, Seq. Id. No. 559,和 Seq. Id. No. 560。
30. 依照權(quán)利要求28-29任一項的方法,其中所述自身抗體識別選自下組的突變型 EGFR 肽: Seq. Id. No. 1, Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7, Seq. Id. No. 15,Seq. Id. No. 16,Seq. Id. No. 17,Seq. Id. No. 18,Seq. Id. No. 19,Seq. Id. No. 20,Seq. Id. No. 21,Seq. Id. No. 22,Seq. Id. No. 23,Seq. Id. No. 24,Seq. Id. No. 25,Seq. Id. No. 26,Seq. Id. No. 27,Seq. Id. No. 28,Seq. Id. No. 29,Seq. Id. No. 30,Seq. Id. No. 31, Seq. Id. No. 32,Seq. Id. No. 33,Seq. Id. No. 34,Seq. Id. No. 35,Seq. Id. No. 36,Seq. Id. No. 37,Seq. Id. No. 38,Seq. Id. No. 39,Seq. Id. No. 40,Seq. Id. No. 41,Seq. Id. No. 42,Seq. Id. No. 43,Seq. Id. No. 44,Seq. Id. No. 45,Seq. Id. No. 46,Seq. Id. No. 47,Seq. Id. No. 48, Seq. Id. No. 49,Seq. Id. No. 50,Seq. Id. No. 51,Seq. Id. No. 52,Seq. Id. No. 53,Seq. Id. No. 54,Seq. Id. No. 55,Seq. Id. No. 56,Seq. Id. No. 57,Seq. Id. No. 58,Seq. Id. No. 59,Seq. Id. No. 60,Seq. Id. No. 61,Seq. Id. No. 62,Seq. Id. No. 63,Seq. Id. No. 65,Seq. Id. No. 66, Seq. Id. No. 67,Seq. Id. No. 68,Seq. Id. No. 69,Seq. Id. No. 70,Seq. Id. No. 71,Seq. Id. No. 72, Seq. Id. No. 73, Seq. Id. No. 74, Seq. Id. No. 75, Seq. Id. No. 76, Seq. Id. No. 77, Seq. Id. No. 78,Seq. Id. No. 79,Seq. Id. No. 80,Seq. Id. No. 81,Seq. Id. No. 82,Seq. Id. No. 83, Seq. Id. No. 84,Seq. Id. No. 85,Seq. Id. No. 86,Seq. Id. No. 87,Seq. Id. No. 88,Seq. Id. No. 89,Seq. Id. No. 90,Seq. Id. No. 91,Seq. Id. No. 92,Seq. Id. No. 93,Seq. Id. No. 94,Seq. Id. No. 95,Seq. Id. No. 96,Seq. Id. No. 97,Seq. Id. No. 98,Seq. Id. No. 99,Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. Ill, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161,Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516, Seq. Id. No. 517, Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527, Seq. Id. No. 528, Seq. Id. No. 529, Seq. Id. No. 530, Seq. Id. No. 531, Seq. Id. No. 532, Seq. Id. No. 533, Seq. Id. No. 534, Seq. Id. No. 535, Seq. Id. No. 536, Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552, Seq. Id. No. 553, Seq. Id. No. 554, Seq. Id. No. 555, Seq. Id. No. 557, Seq. Id. No. 559, Seq. Id. No. 560, Seq. Id. No. 562,Seq. Id. No. 563,Seq. Id. No. 564,Seq. Id. No. 565,Seq. Id. No. 567,Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581, Seq. Id. No. 582, Seq. Id. No. 583,Seq. Id. No. 584,Seq. Id. No. 585,Seq. Id. No. 586,Seq. Id. No. 587,Seq. Id. No. 588,Seq. Id. No. 589,Seq. Id. No. 590,Seq. Id. No. 591,Seq. Id. No. 592,Seq. Id. No. 593,Seq. Id. No. 594,Seq. Id. No. 595,Seq. Id. No. 596,Seq. Id. No. 597,Seq. Id. No. 598,Seq. Id. No. 599,Seq. Id. No. 601,Seq. Id. No. 604,Seq. Id. No. 605,Seq. Id. No. 606,Seq. Id. No. 607,Seq. Id. No. 608,Seq. Id. No. 609,Seq. Id. No. 610,Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 和 Seq. Id. No. 619。
31. 依照權(quán)利要求27-30任一項的方法,其中所述自身抗體識別選自下組的突變 型 EGFR 肽:Seq. Id. No. 1,Seq. Id. No. 2, Seq. Id. No. 4, Seq. Id. No. 5, Seq. Id. No. 6, Seq. Id. No. 7 和 Seq. Id. No. 15。
32. 依照權(quán)利要求27-30任一項的方法,其中所述自身抗體識別選自下組的突變型 EGFR 肽: Seq. Id. No. 16,Seq. Id. No. 17,Seq. Id. No. 18,Seq. Id. No. 19,Seq. Id. No. 20,Seq. Id. No. 21,Seq. Id. No. 22,Seq. Id. No. 23,Seq. Id. No. 24,Seq. Id. No. 25,Seq. Id. No. 26, Seq. Id. No. 27,Seq. Id. No. 28,Seq. Id. No. 29,Seq. Id. No. 30,Seq. Id. No. 31,Seq. Id. No. 32,Seq. Id. No. 33,Seq. Id. No. 34,Seq. Id. No. 35,Seq. Id. No. 36,Seq. Id. No. 37, Seq. Id. No. 38,Seq. Id. No. 39,Seq. Id. No. 40,Seq. Id. No. 41,Seq. Id. No. 42,Seq. Id. No. 43,Seq. Id. No. 44,Seq. Id. No. 45,Seq. Id. No. 46,Seq. Id. No. 47,Seq. Id. No. 48, Seq. Id. No. 49,Seq. Id. No. 50,Seq. Id. No. 51,Seq. Id. No. 52,Seq. Id. No. 53,Seq. Id. No. 54,Seq. Id. No. 55,Seq. Id. No. 56,Seq. Id. No. 57,Seq. Id. No. 58,Seq. Id. No. 59, Seq. Id. No. 60,Seq. Id. No. 61,Seq. Id. No. 62,Seq. Id. No. 63,Seq. Id. No. 65,Seq. Id. No. 66,Seq. Id. No. 67,Seq. Id. No. 68,Seq. Id. No. 69,Seq. Id. No. 70,Seq. Id. No. 71, Seq. Id. No. 72,Seq. Id. No. 73,Seq. Id. No. 74,Seq. Id. No. 75,Seq. Id. No. 76,Seq. Id. No. 77, Seq. Id. No. 78, Seq. Id. No. 79, Seq. Id. No. 80, Seq. Id. No. 81,Seq. Id. No. 82, Seq. Id. No. 83,Seq. Id. No. 84,Seq. Id. No. 85,Seq. Id. No. 86,Seq. Id. No. 87,Seq. Id. No. 88,Seq. Id. No. 89,Seq. Id. No. 90,Seq. Id. No. 91,Seq. Id. No. 92,Seq. Id. No. 93, Seq. Id. No. 94,Seq. Id. No. 95,Seq. Id. No. 96,Seq. Id. No. 97,Seq. Id. No. 98,Seq. Id. No. 99, Seq. Id. No. 100, Seq. Id. No. 101, Seq. Id. No. 103, Seq. Id. No. 104, Seq. Id. No. 105, Seq. Id. No. 106, Seq. Id. No. 107, Seq. Id. No. 108, Seq. Id. No. 109, Seq. Id. No. 110, Seq. Id. No. Ill, Seq. Id. No. 112, Seq. Id. No. 113, Seq. Id. No. 114, Seq. Id. No. 115, Seq. Id. No. 116, Seq. Id. No. 117, Seq. Id. No. 118, Seq. Id. No. 119, Seq. Id. No. 120, Seq. Id. No. 121, Seq. Id. No. 122, Seq. Id. No. 123, Seq. Id. No. 124, Seq. Id. No. 125, Seq. Id. No. 126, Seq. Id. No. 127, Seq. Id. No. 128, Seq. Id. No. 129, Seq. Id. No. 130, Seq. Id. No. 131, Seq. Id. No. 132, Seq. Id. No. 133, Seq. Id. No. 134, Seq. Id. No. 135, Seq. Id. No. 136, Seq. Id. No. 137, Seq. Id. No. 138, Seq. Id. No. 139, Seq. Id. No. 140, Seq. Id. No. 141, Seq. Id. No. 142, Seq. Id. No. 143, Seq. Id. No. 144, Seq. Id. No. 145, Seq. Id. No. 146, Seq. Id. No. 147, Seq. Id. No. 148, Seq. Id. No. 149, Seq. Id. No. 150, Seq. Id. No. 151, Seq. Id. No. 152, Seq. Id. No. 153, Seq. Id. No. 154, Seq. Id. No. 155, Seq. Id. No. 156, Seq. Id. No. 157, Seq. Id. No. 158, Seq. Id. No. 159, Seq. Id. No. 160, Seq. Id. No. 161, Seq. Id. No. 162, Seq. Id. No. 163, Seq. Id. No. 164, Seq. Id. No. 165, Seq. Id. No. 166, Seq. Id. No. 167, Seq. Id. No. 168, Seq. Id. No. 169, Seq. Id. No. 170, Seq. Id. No. 171, Seq. Id. No. 172, Seq. Id. No. 173, Seq. Id. No. 174, Seq. Id. No. 175, Seq. Id. No. 176, Seq. Id. No. 177, Seq. Id. No. 178, Seq. Id. No. 179, Seq. Id. No. 180, Seq. Id. No. 181, Seq. Id. No. 182, Seq. Id. No. 183, Seq. Id. No. 184, Seq. Id. No. 185, Seq. Id. No. 186, Seq. Id. No. 187, Seq. Id. No. 188, Seq. Id. No. 189, Seq. Id. No. 190, Seq. Id. No. 191, Seq. Id. No. 192, Seq. Id. No. 193, Seq. Id. No. 194, Seq. Id. No. 195, Seq. Id. No. 196, Seq. Id. No. 197, Seq. Id. No. 198, Seq. Id. No. 199, Seq. Id. No. 200, Seq. Id. No. 201, Seq. Id. No. 202, Seq. Id. No. 203, Seq. Id. No. 204, Seq. Id. No. 205, Seq. Id. No. 206, Seq. Id. No. 207, Seq. Id. No. 208, Seq. Id. No. 209, Seq. Id. No. 210, Seq. Id. No. 211, Seq. Id. No. 212, Seq. Id. No. 213, Seq. Id. No. 214, Seq. Id. No. 215, Seq. Id. No. 216, Seq. Id. No. 217, Seq. Id. No. 218, Seq. Id. No. 219, Seq. Id. No. 220, Seq. Id. No. 221, Seq. Id. No. 222, Seq. Id. No. 223, Seq. Id. No. 224, Seq. Id. No. 225, Seq. Id. No. 226, Seq. Id. No. 227, Seq. Id. No. 228, Seq. Id. No. 229, Seq. Id. No. 230, Seq. Id. No. 231, Seq. Id. No. 232, Seq. Id. No. 233, Seq. Id. No. 234, Seq. Id. No. 235, Seq. Id. No. 236, Seq. Id. No. 237, Seq. Id. No. 238, Seq. Id. No. 239, Seq. Id. No. 240, Seq. Id. No. 241, Seq. Id. No. 242, Seq. Id. No. 243, Seq. Id. No. 244, Seq. Id. No. 245, Seq. Id. No. 246, Seq. Id. No. 247, Seq. Id. No. 248, Seq. Id. No. 249, Seq. Id. No. 250, Seq. Id. No. 251, Seq. Id. No. 252, Seq. Id. No. 253, Seq. Id. No. 254, Seq. Id. No. 255, Seq. Id. No. 256, Seq. Id. No. 257, Seq. Id. No. 258, Seq. Id. No. 259, Seq. Id. No. 260, Seq. Id. No. 261, Seq. Id. No. 262, Seq. Id. No. 263, Seq. Id. No. 264, Seq. Id. No. 265, Seq. Id. No. 266, Seq. Id. No. 267, Seq. Id. No. 268, Seq. Id. No. 269, Seq. Id. No. 270, Seq. Id. No. 271, Seq. Id. No. 272, Seq. Id. No. 273, Seq. Id. No. 274, Seq. Id. No. 275, Seq. Id. No. 276, Seq. Id. No. 277, Seq. Id. No. 278, Seq. Id. No. 279, Seq. Id. No. 280, Seq. Id. No. 281, Seq. Id. No. 282, Seq. Id. No. 283, Seq. Id. No. 284, Seq. Id. No. 285, Seq. Id. No. 286, Seq. Id. No. 287, Seq. Id. No. 288, Seq. Id. No. 289, Seq. Id. No. 290, Seq. Id. No. 291, Seq. Id. No. 292, Seq. Id. No. 293, Seq. Id. No. 294, Seq. Id. No. 295, Seq. Id. No. 296, Seq. Id. No. 297, Seq. Id. No. 298, Seq. Id. No. 299, Seq. Id. No. 300, Seq. Id. No. 301, Seq. Id. No. 302, Seq. Id. No. 303, Seq. Id. No. 304, Seq. Id. No. 305, Seq. Id. No. 306, Seq. Id. No. 307, Seq. Id. No. 308, Seq. Id. No. 310, Seq. Id. No. 311, Seq. Id. No. 312, Seq. Id. No. 313, Seq. Id. No. 314, Seq. Id. No. 315, Seq. Id. No. 316, Seq. Id. No. 317, Seq. Id. No. 318, Seq. Id. No. 319, Seq. Id. No. 320, Seq. Id. No. 321, Seq. Id. No. 322, Seq. Id. No. 323, Seq. Id. No. 324, Seq. Id. No. 325, Seq. Id. No. 326, Seq. Id. No. 327, Seq. Id. No. 328, Seq. Id. No. 329, Seq. Id. No. 330, Seq. Id. No. 331, Seq. Id. No. 332, Seq. Id. No. 333, Seq. Id. No. 334, Seq. Id. No. 335, Seq. Id. No. 336, Seq. Id. No. 337, Seq. Id. No. 338, Seq. Id. No. 339, Seq. Id. No. 340, Seq. Id. No. 341, Seq. Id. No. 342, Seq. Id. No. 343, Seq. Id. No. 344, Seq. Id. No. 345, Seq. Id. No. 346, Seq. Id. No. 347, Seq. Id. No. 348, Seq. Id. No. 349, Seq. Id. No. 350, Seq. Id. No. 351, Seq. Id. No. 352, Seq. Id. No. 353, Seq. Id. No. 354, Seq. Id. No. 355, Seq. Id. No. 356, Seq. Id. No. 357, Seq. Id. No. 358, Seq. Id. No. 359, Seq. Id. No. 360, Seq. Id. No. 361, Seq. Id. No. 362, Seq. Id. No. 363, Seq. Id. No. 364, Seq. Id. No. 365, Seq. Id. No. 366, Seq. Id. No. 367, Seq. Id. No. 368, Seq. Id. No. 369, Seq. Id. No. 371, Seq. Id. No. 372, Seq. Id. No. 374, Seq. Id. No. 375, Seq. Id. No. 376, Seq. Id. No. 377, Seq. Id. No. 378, Seq. Id. No. 379, Seq. Id. No. 380, Seq. Id. No. 381, Seq. Id. No. 382, Seq. Id. No. 383, Seq. Id. No. 384, Seq. Id. No. 385, Seq. Id. No. 386, Seq. Id. No. 387, Seq. Id. No. 388, Seq. Id. No. 389, Seq. Id. No. 390, Seq. Id. No. 391, Seq. Id. No. 392, Seq. Id. No. 393, Seq. Id. No. 394, Seq. Id. No. 395, Seq. Id. No. 396, Seq. Id. No. 397, Seq. Id. No. 398, Seq. Id. No. 399, Seq. Id. No. 400, Seq. Id. No. 401, Seq. Id. No. 402, Seq. Id. No. 403, Seq. Id. No. 404, Seq. Id. No. 405, Seq. Id. No. 406, Seq. Id. No. 407, Seq. Id. No. 408, Seq. Id. No. 409, Seq. Id. No. 410, Seq. Id. No. 411, Seq. Id. No. 412, Seq. Id. No. 413, Seq. Id. No. 414, Seq. Id. No. 415, Seq. Id. No. 416, Seq. Id. No. 417, Seq. Id. No. 418, Seq. Id. No. 419, Seq. Id. No. 420, Seq. Id. No. 421, Seq. Id. No. 422, Seq. Id. No. 423, Seq. Id. No. 424, Seq. Id. No. 425, Seq. Id. No. 426, Seq. Id. No. 427, Seq. Id. No. 428, Seq. Id. No. 429, Seq. Id. No. 430, Seq. Id. No. 431, Seq. Id. No. 432, Seq. Id. No. 433, Seq. Id. No. 434, Seq. Id. No. 435, Seq. Id. No. 436, Seq. Id. No. 437, Seq. Id. No. 438, Seq. Id. No. 439, Seq. Id. No. 440, Seq. Id. No. 441, Seq. Id. No. 442, Seq. Id. No. 443, Seq. Id. No. 444, Seq. Id. No. 445, Seq. Id. No. 446, Seq. Id. No. 447, Seq. Id. No. 448, Seq. Id. No. 449, Seq. Id. No. 450, Seq. Id. No. 451, Seq. Id. No. 452, Seq. Id. No. 453, Seq. Id. No. 454, Seq. Id. No. 455, Seq. Id. No. 456, Seq. Id. No. 457, Seq. Id. No. 458, Seq. Id. No. 459, Seq. Id. No. 460, Seq. Id. No. 461, Seq. Id. No. 462, Seq. Id. No. 463, Seq. Id. No. 464, Seq. Id. No. 465, Seq. Id. No. 466, Seq. Id. No. 467, Seq. Id. No. 468, Seq. Id. No. 469, Seq. Id. No. 470, Seq. Id. No. 471, Seq. Id. No. 472, Seq. Id. No. 473, Seq. Id. No. 474, Seq. Id. No. 475, Seq. Id. No. 476, Seq. Id. No. 477, Seq. Id. No. 478, Seq. Id. No. 479, Seq. Id. No. 480, Seq. Id. No. 481, Seq. Id. No. 482, Seq. Id. No. 483, Seq. Id. No. 484, Seq. Id. No. 485, Seq. Id. No. 486, Seq. Id. No. 487, Seq. Id. No. 488, Seq. Id. No. 489, Seq. Id. No. 490, Seq. Id. No. 491, Seq. Id. No. 492, Seq. Id. No. 493, Seq. Id. No. 494, Seq. Id. No. 495, Seq. Id. No. 496, Seq. Id. No. 497, Seq. Id. No. 498, Seq. Id. No. 499, Seq. Id. No. 500, Seq. Id. No. 501, Seq. Id. No. 502, Seq. Id. No. 503, Seq. Id. No. 504, Seq. Id. No. 505, Seq. Id. No. 506, Seq. Id. No. 507, Seq. Id. No. 508, Seq. Id. No. 509, Seq. Id. No. 510, Seq. Id. No. 511, Seq. Id. No. 512, Seq. Id. No. 513, Seq. Id. No. 514, Seq. Id. No. 515, Seq. Id. No. 516 和 Seq. Id. No. 517。
33.依照權(quán)利要求27-30任一項的方法,其中所述自身抗體識別選自下組的突變型 EGFR 肽: Seq. Id. No. 518, Seq. Id. No. 522, Seq. Id. No. 523, Seq. Id. No. 524, Seq. Id. No. 526, Seq. Id. No. 527,Seq. Id. No. 528,Seq. Id. No. 529,Seq. Id. No. 530,Seq. Id. No. 531,Seq. Id. No. 532,Seq. Id. No. 533,Seq. Id. No. 534,Seq. Id. No. 535,Seq. Id. No. 536,Seq. Id. No. 537, Seq. Id. No. 538, Seq. Id. No. 539, Seq. Id. No. 540, Seq. Id. No. 541, Seq. Id. No. 542, Seq. Id. No. 543, Seq. Id. No. 544, Seq. Id. No. 545, Seq. Id. No. 546, Seq. Id. No. 547, Seq. Id. No. 548, Seq. Id. No. 549, Seq. Id. No. 550, Seq. Id. No. 551, Seq. Id. No. 552,Seq. Id. No. 553,Seq. Id. No. 554,Seq. Id. No. 555,Seq. Id. No. 557,Seq. Id. No. 559,Seq. Id. No. 560,Seq. Id. No. 562,Seq. Id. No. 563,Seq. Id. No. 564,Seq. Id. No. 565, Seq. Id. No. 567, Seq. Id. No. 568, Seq. Id. No. 569, Seq. Id. No. 570, Seq. Id. No. 571, Seq. Id. No. 572, Seq. Id. No. 573, Seq. Id. No. 574, Seq. Id. No. 575, Seq. Id. No. 576, Seq. Id. No. 577, Seq. Id. No. 578, Seq. Id. No. 579, Seq. Id. No. 580, Seq. Id. No. 581,Seq. Id. No. 582,Seq. Id. No. 583,Seq. Id. No. 584,Seq. Id. No. 585,Seq. Id. No. 586,Seq. Id. No. 587,Seq. Id. No. 588,Seq. Id. No. 589,Seq. Id. No. 590,Seq. Id. No. 591,Seq. Id. No. 592,Seq. Id. No. 593,Seq. Id. No. 594,Seq. Id. No. 595,Seq. Id. No. 596, Seq. Id. No. 597, Seq. Id. No. 598, Seq. Id. No. 599 和 Seq. Id. No. 601。
34. 依照權(quán)利要求27-30任一項的方法,其中所述自身抗體識別選自下組的突變 型 EGFR 肽:569.1(1.此.604,569.1(1.此.605,569.1(1.此.606,569.1(1.此.607,569. Id. No. 608, Seq. Id. No. 609, Seq. Id. No. 610, Seq. Id. No. 611, Seq. Id. No. 612, Seq. Id. No. 613, Seq. Id. No. 614, Seq. Id. No. 615, Seq. Id. No. 616, Seq. Id. No. 617, Seq. Id. No. 618 和 Seq. Id. No. 619。
35. 依照權(quán)利要求27-34任一項的方法,其中該人受試者的血液樣品中自身抗體的水 平比代表健康群體人受試者的所述自身抗體的水平高5倍。
36. -種在人受試者中診斷非小細(xì)胞肺癌的方法,其包括: a) 在該人受試者的血液樣品中測量選自識別人EGFR的自身抗體組的自身抗體的水 平, b) 比較所述自身抗體的水平與參照水平,并 c) 當(dāng)所述自身抗體的水平超出參照水平時提供非小細(xì)胞肺癌的診斷。
37. -種在人受試者中診斷非小細(xì)胞肺癌的方法,其包括: a) 在該人受試者的血液樣品中測量選自識別人EGFR的自身抗體組的自身抗體的水 平, b) 比較所述自身抗體的水平與參照水平,并 c) 當(dāng)所述自身抗體的水平超出參照水平時推薦治療。
38. 依照權(quán)利要求36或37的方法,其中所述自身抗體識別選自下組的EGFR肽:Seq. Id. No. 3,Seq. Id. No. 8,Seq. Id. No. 9,Seq. Id. No. 10,Seq. Id. No. 11,Seq. Id. No. 12,Seq. Id. No. 13, Seq. Id. No. 14, Seq. Id. No. 64, Seq. Id. No. 102, Seq. Id. No. 309, Seq. Id. No. 370, Seq. Id. No. 373,Seq. Id. No. 519,Seq. Id. No. 520,Seq. Id. No. 521,Seq. Id. No. 525,Seq. Id. No. 556,Seq. Id. No. 558,Seq. Id. No. 561,Seq. Id. No. 566,Seq. Id. No. 600,Seq. Id. No. 602 和 Seq. Id. No. 603。
39. 依照權(quán)利要求36-38任一項的方法,其中該人受試者的血液樣品中自身抗體的水 平比代表健康群體人受試者的所述自身抗體的水平高5倍。
40. 依照權(quán)利要求28-35、37-39任一項的方法,其中所述治療為厄洛替尼。
41. 說明書中描述的發(fā)明。
【文檔編號】G01N33/574GK104334190SQ201380027063
【公開日】2015年2月4日 申請日期:2013年6月4日 優(yōu)先權(quán)日:2012年6月7日
【發(fā)明者】P·伯恩特, B·克盧格哈默 申請人:霍夫曼-拉羅奇有限公司