METHOD, ARRAY AND USE THEREOF
20220206004 · 2022-06-30
Inventors
- Carl BORREBAECK (Lund, SE)
- Anna Sandström Gerdtsson (Karlshamm, SE)
- Christer WINGREN (Södra Sandby, SE)
Cpc classification
G01N33/57484
PHYSICS
G01N2800/56
PHYSICS
International classification
Abstract
The present invention provides a method for diagnosing or determining a pancreatic cancer-associated disease state comprising or consisting of the steps of: (a) providing a sample from an individual to be tested; and (b) determining a biomarker signature of the test sample by measuring the presence and/or amount in the test sample of one or more biomarker selected from the group defined in Table A; wherein the presence and/or amount in the test sample of the one or more biomarker selected from the group defined in Table A is indicative of the pancreatic cancer-associated disease in the individual; uses and methods of determining a pancreatic cancer-associated disease state, and methods of treating pancreatic cancer, together with arrays and kits for use in the same.
Claims
1: A method for diagnosing or determining a pancreatic cancer-associated disease state comprising the steps of: (a) providing a sample from an individual to be tested; and (b) determining a biomarker signature of the test sample by measuring the presence and/or amount in the test sample of one or more biomarker selected from the group defined in Table A; wherein the presence and/or amount in the test sample of the one or more biomarker selected from the group defined in Table A is indicative of the pancreatic cancer associated disease in the individual, optionally wherein said pancreatic cancer-associated disease state is (i) diagnosis and/or staging of early pancreatic cancer; or (ii) diagnosis and/or staging of pancreatic cancer.
2-5. (canceled)
6: The method according to claim 1, wherein the method is for the diagnosis of stage I or stage II pancreatic cancer, wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker listed in: (i) Table A(I); (ii) Table A(III); (iii) Table A(V); and (iv) Table A(XI); and/or wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker listed in: (i) Table A(II); (ii) Table A(IV); (iii) Table A(VI); and (iv) Table A(XII).
7. (canceled)
8. (canceled)
9: The method according to claim 1, wherein the method is for the diagnosis of stage I pancreatic cancer, wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker listed in: (i) Table A(I); (ii) Table A(III); and (iii) Table A(VII); and/or wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker listed in: (i) Table A(II); (ii) Table A(IV); and (iii) Table A(VIII).
10. (canceled)
11. (canceled)
12: The method according to claim 1, wherein the method is for the diagnosis of stage II pancreatic cancer, wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker listed in: (iv) Table A(I); (v) Table A(V); (vi) Table A(IX); and/or wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker listed in: (iv) Table A(II); (v) Table A(VI); and (vi) Table A(X).
13. (canceled)
14. (canceled)
15: The method according to claim 1, wherein the pancreatic cancer-associated disease state is pancreatic cancer, wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker selected from the group consisting of CHP-1, MAPKK 2, UBP7, PRD14, STAT1, AGAP-2, PGAM5, LUM, PTPRO and USP07.
16: The method according to claim 15 wherein step (b) comprises measuring the presence and/or amount of 1 or more biomarker selected from the group consisting of Apo-A1, BTK, C1q, C5, CDK-2, IgM, IL-11, IL-12, IL-6, JAK3, MAPK8, MCP-1, MUC-1, Properdin, VEGF, C3, ICAM-1, IL-13, ATP-5B, C4, Her2/ErB-2, IL-7, IL-3, IL-8, GM-CSF, IL-9, LDL and ORP3.
17. (canceled)
18: The method according to claim 1, further comprising the steps of: c) providing one or more control sample from: i) an individual not afflicted with pancreatic cancer; and/or ii) an individual afflicted with pancreatic cancer, wherein the sample was of a different stage to that of that the test sample; d) determining a biomarker signature of the one or more control sample by measuring the presence and/or amount in the control sample of the one or more biomarkers measured in step (b); wherein the pancreatic cancer-associated disease state is identified in the event that the presence and/or amount in the test sample of the one or more biomarkers measured in step (b) is different from the presence and/or amount in the control sample of the one or more biomarkers measured in step (d); and/or further comprising the steps of: e) providing one or more control sample from; i) an individual afflicted with pancreatic cancer; and/or ii) an individual afflicted with pancreatic cancer, wherein the sample was of the same stage to that of that the test sample; f) determining a biomarker signature of the control sample by measuring the presence and/or amount in the control sample of the one or more biomarkers measured in step (b); wherein the pancreatic cancer-associated disease state is identified in the event that the presence and/or amount in the test sample of the one or more biomarkers measured in step (b) corresponds to the presence and/or amount in the control sample of the one or more biomarkers measured in step (f).
19. (canceled)
20: The method according to claim 18, wherein the individual from which the one or more control sample was obtained was not, at the time the sample was obtained, afflicted with a non-cancerous pancreatic disease or condition; wherein the individual from which the one or more control sample was obtained was not, at the time the sample was obtained, afflicted with any disease or condition of the pancreas; wherein the individual not afflicted with pancreatic cancer was not, at the time the sample was obtained, afflicted with any disease or condition; wherein the individual not afflicted with pancreatic cancer is a healthy individual; and/or wherein the one or more individual afflicted with pancreatic cancer is afflicted with a pancreatic cancer selected from the group consisting of adenocarcinoma, pancreatic sarcoma, malignant serous cystadenoma, adenosquamous carcinoma, signet ring cell carcinoma, hepatoid carcinoma, colloid carcinoma, undifferentiated carcinoma, and undifferentiated carcinomas with osteoclast-like giant cells.
21-24. (canceled)
25: The method according to claim 1, wherein the pancreatic cancer is pancreatic adenocarcinoma.
26: The method according to claim 1, wherein the method is repeated, and optionally wherein, in step (a), the sample to be tested is taken at different time to the previous method repetition; wherein the method is repeated using a test sample taken at a different time period to the previous test sample(s) used; wherein the method is repeated using a test sample taken between 1 day to 104 weeks to the previous test sample(s) used; wherein the method is repeated using a test sample taken every period from the group consisting of: 1 day, 2 days, 3 day, 4 days, 5 days, 6 days, 7 days, 10 days, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 15 weeks, 20 weeks, 25 weeks, 30 weeks, 35 weeks, 40 weeks, 45 weeks, 50 weeks, 55 weeks, 60 weeks, 65 weeks, 70 weeks, 75 weeks, 80 weeks, 85 weeks, 90 weeks, 95 weeks, 100 weeks, 104, weeks, 105 weeks, 110 weeks, 115 weeks, 120 weeks, 125 weeks and 130 weeks; wherein the method is repeated at least 2 times; wherein the method is repeated continuously; wherein the method is repeated until pancreatic cancer is diagnosed in the individual using conventional clinical methods; and/or wherein each repetition uses test sample taken from the same individual.
27-34. (canceled)
35: The method according to claim 1, wherein step (b) comprises measuring the expression of the protein or polypeptide of the one or more biomarker(s), optionally using an array.
36: The method according to claim 1, wherein step (b) is performed using one or more first binding agent capable of binding to a biomarker listed in Table A, optionally wherein the first binding agent is immobilized on a surface; wherein the first binding agent comprises an antibody or an antigen-binding fragment thereof; wherein the one or more biomarkers in the test sample are labelled with a detectable moiety; and/or wherein the one or more biomarkers in the control sample(s) are labelled with a detectable moiety.
37-44. (canceled)
45: The method according to claim 36, wherein step (b) is performed using an assay comprising a second binding agent capable of binding to the one or more biomarkers, the second binding agent comprising a detectable moiety, optionally wherein the second binding agent comprises an antibody or an antigen-binding fragment thereof.
46-55. (canceled)
56: The method according to claim 1, wherein the method comprises: (i) labelling biomarkers present in the sample with biotin; (ii) contacting the biotin-labelled proteins with an array comprising a plurality of scFv immobilised at discrete locations on its surface, the scFv having specificity for one or more of the proteins in Table A; (iii) contacting the immobilised scFv with a streptavidin conjugate comprising a fluorescent dye; and (iv) detecting the presence of the dye at discrete locations on the array surface wherein the expression of the dye on the array surface is indicative of the expression of a biomarker from Table III in the sample.
57: The method according to claim 1, wherein step (b) comprises measuring the expression of a nucleic acid molecule encoding the one or more biomarkers, optionally using a method selected from the group consisting of Southern hybridisation, Northern hybridisation, polymerase chain reaction (PCR), reverse transcriptase PCR (RT PCR), quantitative real-time PCR (qRT-PCR), nanoarray, microarray, macroarray, autoradiography and in situ hybridisation.
58-72. (canceled)
73: The method according to claim 1, wherein the sample provided in step (a) is selected from the group consisting of unfractionated blood, plasma, serum, tissue fluid, pancreatic tissue, milk, bile and urine.
74-77. (canceled)
78: The method according to claim 1, wherein in the event that the individual is diagnosed with pancreatic cancer, the method comprises the step of: (g) providing the individual with pancreatic cancer therapy, optionally selected from the group consisting of surgery, chemotherapy, immunotherapy, chemoimmunotherapy and thermochemotherapy.
79. (canceled)
80: An array for determining the presence of pancreatic cancer in an individual comprising one or more binding agent, wherein said binding agent is capable of binding to a biomarker listed in Table A.
81-85. (canceled)
86: A kit for determining the presence of pancreatic cancer comprising: A) one or more binding agent, wherein said binding agent is capable of binding to a biomarker listed in Table A, optionally wherein said one or more binding agent is contained within an array; B) instructions for performing the method.
87: A method of treating pancreatic cancer in an individual comprising the steps of: (a) diagnosing pancreatic cancer according to the method defined in claim 1; and (b) providing the individual with pancreatic cancer therapy optionally selected from the group consisting of surgery, chemotherapy, immunotherapy, chemoimmunotherapy and thermochemotherapy.
88-90. (canceled)
Description
[0306] Preferred, non-limiting examples which embody certain aspects of the invention will now be described, with reference to the following tables and figures:
[0307]
[0308] (
[0309]
[0310] A training set and a test set was generated by randomized selection of 2/3 of samples from each group (PDAC and NC) to the training set, and the remaining 1/3 of samples to the test set. The training set was used to define a condensed signature for discriminating PDAC from NC. (
[0311]
[0312]
[0313]
[0314] Serum from 156 PDAC patients collected at 5 different sites in Spain for the PANKRAS II [Parker et al., 2011, Porta et al., 1999] study (Gerdtsson et al., 2016, Mol Oncol. 10(8):1305-16).
[0315] “UP”=up-regulated, “DOWN”=down-regulated in Head vs Body/Tail tumors, N/A=antibody not included in study.
[0316]
[0317]
EXAMPLE
[0318] Abstract
[0319] In this study, a recombinant antibody microarray platform was used to analyse 213 plasma samples from pancreatic cancer patients and normal control individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). SVM analysis showed that all PDAC stages could be discriminated from controls. This is the first time patients with stage I/II PDAC tumours could be discriminated from controls with high accuracy based on a plasma protein signature, which indicates a possibility for early diagnosis and an increased rate of surgically resectable tumors.
[0320] Introduction
[0321] Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a 5-year survival rate of 3-4%. A key driver behind this poor prognosis is the current inability to diagnose patients at an early stage. Data supports that it takes more than five years from tumor initiation until the acquisition of metastatic ability (Yachida et al., 2010), which clearly demonstrates a window of opportunity for early detection if accurate markers were available. At the time of diagnosis, patients have often developed late-stage disease, and only approximately 15% of the patients have resectable tumors (Conlon et al., 1996; Sohn et al., 2000). The 5-year survival of these patients, displaying large resected tumors, is only 10-20% (Conlon et al., 1996; Sohn et al., 2000). However, the 5-year survival increases to 30-60% if tumors≤20 mm (Stage I-II) can be resected (Furukawa et al., 1996; Shimizu et al., 2005). The late diagnosis (Stage III-IV) is due to unspecific clinical symptoms in combination with the lack of markers for early diagnosis, something which is addressed in this study. Interestingly, studies suggest that pancreatic tumors could be resectable as early as six months prior to clinical diagnosis at an asymptomatic stage (Gangi et al., 2004; Pelaez-Luna et al., 2007).
[0322] The so far most evaluated marker for PDAC, CA19-9, suffers from poor specificity, with elevated levels in several other indications, as well as a complete absence in patients that are genotypically Lewis a-b- (5% of the population). Consequently, the use of CA19-9 for pancreatic cancer screening is not recommended (Locker et al., 2006). Today, no other single biomarker has been shown to accurately diagnose PDAC, although recent discovery studies have demonstrated that both exosomes and nucleosomes contain information associated with pancreatic cancer (Bauden et al., 2015; Melo et al., 2015). However, the field of cancer diagnostics is today moving towards panels of markers, since this yields increased sensitivity and specificity (Brand et al., 2011; Bunger et al., 2011).
[0323] Inflammation seems to be a critical component of tumor progression (Coussens and Werb, 2002) and the immunoregulatory plasma proteome may consequently be a source of potential cancer biomarkers.
[0324] Previous studies have also demonstrated that an increased number (n=20-25) of immunoregulatory proteins will yield highly disease-specific signatures, reflecting a systemic response to disease (Carlsson et al., 2011b; Ingvarsson et al., 2008; Wingren et al., 2012). However, analysis of the immunoregulatory proteome is associated with several challenges, such as, (i) plasma proteins display a vast dynamic concentration range; (ii) cancer markers are more likely to be found among the most low-abundant proteins (Haab et al., 2005; Surinova et al., 2011); (iii) disease-associated changes in plasma levels of low-abundant markers is expected to be small, requiring a significant number of samples for adequate statistics (Alonzo et al., 2002).
[0325] To meet these challenges, we have in the present study analyzed 213 plasma samples from Chinese patients with pancreatic cancer Stage I-IV and normal controls, using a sensitive antibody microarray platform. The aim was to identify stage-associated PDAC markers by comparing control samples to stage I-IV and the results support the concept that the information content in a simple blood sample is enough to find even the earlier disease stages. Consequently, enables early diagnosis of PDAC, particularly for the benefit of patients at high risk, such as chronic pancreatitis, hereditary PDAC, and Peutz-Jeghers syndrome patients.
[0326] Material and Methods
[0327] Plasma Samples
[0328] This retrospective study was approved by the Ethics Committee of Tianjin Medical University Cancer Institute and Hospital (TMUCIH). After informed consent, blood was collected at TMUCIH, plasma was isolated and stored at −80° C. A total of 213 plasma samples, collected from Jan. 1, 2012 to Dec. 13, 2013, were used (Table 1). The enrolled PDAC patients (n=118) were all Chinese Han ethnicity and treated at TMUCIH. None of the patients had received chemotherapy or radiotherapy at the time of blood draw. All PDAC samples were cytology confirmed by experienced pathologists. Patients were diagnosed with pancreatic ductal adenocarcinoma with the following exceptions: Malignant serous cystadenoma (n=1), pancreatic sarcoma (n=2), tubular papillary pancreatic adenocarcinoma (n=1). Five patients were diagnosed with PDAC with liver metastasis. Data on tumor stage and size at diagnosis, and tumor location within the pancreas were based on clinical pathology. Staging was performed according to the American Cancer Society's guidelines (Table 1) and the extent of resection was classified as RO. Normal control (NC) samples (n=95) were collected from healthy inhabitants of Tianjin at their routine physical examination at TMUCIH, and were genetically unrelated to the PDAC patients (Table 1). Sample IDs were recoded and randomized at labelling, and sample annotation and clinical data was blinded to the operator at all downstream experimental procedures. All samples were labelled at one single occasion, using a previously optimized protocol (Wingren et al., 2012).
[0329] Generation of Antibody Microarrays
[0330] The antibody microarrays contained 350 human recombinant scFv antibodies, selected and generated from in-house designed phage display antibody libraries, produced in E. coli as previously been described (Pauly et al., 2014) and printed onto slides in 14 arrays/slide and 3 replicate spots/array. All slides used for this study were printed at a single occasion, shipped to TMUCIH in China, and used for analysis within 4 weeks after printing.
[0331] Antibody Microarray Analysis
[0332] Ten slides (140 individual subarrays) were processed per day with randomized sample order. Briefly, arrays were blocked with PBSMT, washed with PBST, and incubated with biotinylated plasma samples for 2 h at RT. Unbound proteins were washed off, and bound proteins were detected using 1 μg/mL Alexa Fluor647-Streptavidin (1 h at RT). Excess reagent was washed off, and slides were dried and immediately scanned in a LuxScan 10K Microarray scanner (CapitalBio) at 10 μm resolution using the 635 nm and the 532 nm excitation lasers.
[0333] Data Acquisition, Quality Control and Pre-Processing
[0334] Signal intensities were quantified by two trained analysts (ASG and MN), blinded to patient ID and clinical data, using the ScanArray Express software version 4.0 (PerkinElmer Life and Analytical Sciences) with the fixed-circle option. For each microarray a grid was positioned, using the Alexa Fluor555 signals from microarray printing, and used to quantify the Alexa Fluor647 signal corresponding to the relative level of bound protein. Eleven samples (10 PDAC, 1 NC) were not quantified due to poor quality images resulting from of high background and/or low overall signals. For quantified arrays, the spot saturation, mean intensity and signal-to-noise ratio of each spot were evaluated. Fourteen antibodies were excluded because (i) the median signal intensity was below the cut-off limit, defined as the background (average PBS signal)+2 standard deviations (n=8), (ii) saturated signal in the lowest scanner intensity setting in more than 50% of samples (n=1), and (iii) inadequate antibody printing (n=5). Based on the remaining 202 samples and 336 antibodies, a dataset was assembled using the mean spot intensity after local background subtraction. Each data point represented an average of the 3 replicate spots, unless any replicate CV exceeded 15% from the mean value, in which case it was discarded and the average of the 2 remaining replicates was used instead. The average CV of replicates was 7.9% (±4.1%). Applying a cut-off CV of 15%, 79% of data values were calculated from all 3 replicates and the remaining 21% from 2 replicates. Furthermore, patients with jaundice (n=27) were compared to patients without jaundice (n=81), to analyze whether the bilirubin level was a confounding factor in the antibody microarray analysis. Similarly, a gender-adjusted dataset was generated to assess whether gender was a confounding factor. The logged data was normalized, using the empirical Bayes algorithm ComBat (Johnson et al., 2007) for adjusting technical variation, followed by a linear scaling of data from each array to adjust for variations in sample background level. The scaling factor was based on the 20% of antibodies with the lowest standard deviation across all samples and was calculated by dividing the intensity sum of these antibodies on each array with the average sum across all arrays (Carlsson et al., 2008; Ingvarsson et al., 2008).
[0335] Data Analysis
[0336] The sample and variable distribution was analyzed and visualized, using a principal component analysis based program (QIucore, Lund, Sweden). ANOVA was applied for an initial filtering of data. The performance of individual markers was evaluated using Wilcoxon or Student's t-test, Benjamini Hochberg procedure for false discovery rate control, and fold changes. Separation of different subgroups was assessed using support vector machine (SVM), applying a linear kernel with the cost of constraints set to 1. Models for discriminating two groups were created, using a leave-one-out cross validation procedure.
[0337] To minimize over-interpretation and to demonstrate robustness of the data set, it was randomly divided into training and test sets, and the SVM-based backward elimination algorithm was applied in the training sets. Consequently, biomarker signatures were generated in training sets of the data, consisting of 2/3 of the total samples from each subgroup, and evaluated in a test sets containing the remaining 1/3 of samples. In training sets, filtering was performed using an SVM-based Backward Elimination algorithm, as previously described (Carlsson et al., 2011a) and models based on the resulting antibody signatures were tested in the corresponding test sets. Ten different pairs of training and test sets were used for this purpose, resulting in a consensus list in which each antibody was given an elimination score corresponding to its median order of elimination in the 10 training sets. The performance was assessed using receiver operating characteristics (ROC) curves and reported as area under the curve (AUC) values. The sensitivity and specificity, positive and negative predictive values of each signature in its respective test set were noted for the SVM decision value threshold corresponding to the maximum sum of sensitivity and specificity.
[0338] Results
[0339] Discrimination Between Cases and Controls and Identification of Plasma Protein Signatures Associated with Pancreatic Cancer
[0340] Initially, we show that PDAC cases can be discriminated from normal controls, using PCA, q-value filtration and SVM analysis with leave-on-out cross validation. Principal component analysis revealed a moderate separation of PDAC and NC samples (
[0341] The high level of differentiation between PDAC and NC using unfiltered data (AUC 0.88) motivated in-depth data filtering for identifying a condensed PDAC-associated protein signature. To avoid over-fitting the model to the data, samples were first separated into training sets for generating antibody signatures models which were then evaluated on separate test sets. In the training sets, antibodies were filtered using SVM-based backward elimination and the Kullback-Leibler (K-L) error in the classification was plotted against the number of eliminated antibodies.
[0342] Each antibody was scored based on the reverse order of elimination, with number 1 being the last antibody to be eliminated, and ranked in order of their median elimination score from the 10 sequential elimination rounds. Table 2 lists the 25 highest ranked antibodies, with their p- and q-values, the p-value ranking, and the fold change for PDAC vs. NC. The top 2 antibodies Properdin and VEGF with median elimination scores of 1 and 2, respectively, were the last eliminated antibodies in 9/10 (Properdin), and the second last eliminated in 8/10 (VEGF) training sets. The top 25 ranked antibodies together represented 20 different specificities.
[0343] The backward elimination procedure was designed to identify the optimal combination of antibodies, not taking into consideration one-dimensional separation of data based on individual antibodies, and the consensus signature presented in Table 2 is based solely on the backward elimination ranking. Of note, the top two antibodies were also the two highest ranked on basis of p- and q-values. In fact, the five highest ranked antibodies all displayed highly significant p- and q-values for PDAC vs. NC (p<4.47E-06 and q<5.00E-04). The backward elimination rank (BE-score) and the t-test rank (W-score) for the consensus signature antibodies were plotted together in
[0344] Discrimination Between Stage I-IV of Pancreatic Cancer
[0345] Discrimination between different disease stages is of high interest since this is associated with the ability to diagnose pancreatic cancer in its non-invasive stage. In an attempt to assess the significance of identified markers for early diagnosis, the PDAC samples were stratified according to disease stage. SVM with leave-one-out cross validation showed that all PDAC stages were separated from NC and that classification accuracy increased with disease progression, with AUC-values of 0.71, 0.86, 0.90 and 0.93 for discriminating NC from stage I, II, III, and IV, respectively (
[0346]
[0347] It is noteworthy that in our previous study on serum markers in Stage III/IV Caucasian PDAC patients, C5 was ranked as the most prominent marker in a backward elimination filtering analysis, while the current study ranked the same antibody as number 14 (Table 2). However, when stage-specific analysis was performed it was evident that C5 was elevated only in late stage disease, which is coherent with the former study (Wingren et al., 2012). Of note, the stage-specific analysis pointed out several early marker candidate proteins, e.g. elevated levels of BKT, CDK2, MAPK-8, AGAP-2, IL-13, IL-6, PTPRO, USP-7, MUC-1, and reduced levels of Apo-A1 and C1q measurable already at stage I/II disease.
[0348] Markers Associated with Tumor Location
[0349] The samples were also grouped by the primary tumor location in the pancreas, and plasma from tumors located in the head of pancreas was compared to those located in the body and/or tail of pancreas. Samples with tumors at other locations (neck=4, neck+body=1, head+tail=1) were excluded from this analysis. Applying a cut-off of Wilcoxon p<0.05, 37 antibodies showed significantly different intensity levels in Head vs. Body/Tail (
[0350] Correlation Between Markers Derived from Caucasian and Chinese Populations
[0351] We next assessed the concordance of the plasma protein signature in the Chinese pancreatic cancer subjects with the serum protein signature previously identified in a late stage PDAC Caucasian cohort, analyzed in relation to healthy controls as well as to patients with pancreatitis (Wingren et al., 2012). Of note, the antibody microarray content has expanded significantly since the former study, making correlation measures of the two studies difficult. The former study only contained 36% of the antibodies currently used and did for example not include the core marker CHP-1. However, the other four core signature proteins (Properdin, VEGF, IL-8 and C3) were all part of the previously published serum PDAC signature. In addition to the core panel, there was a clear overlap between the two ethnic cohorts when comparing the 25 highest ranked antibodies in the two studies (Table 2), demonstrating that blood-based proteomics analysis is less affected by the genetic make-up of sample donors (Caucasian/Asian), or sample format (serum/plasma).
[0352] In the previous Caucasian cohort it was also shown that PDAC could be differentiated both from controls and pancreatitis (Wingren et al., 2012). Since our Asian cohort did not include chronic pancreatitis samples, we instead compared significant (Wilcoxon p<0.05) markers present in this and previous studies (Sandstrom et al., 2012; Wingren et al., 2012). Five markers (C3, C5, IL-12, IL-8, Properdin) were commonly expressed in both serum and plasma PDAC samples, as well as in pancreatitis samples. Despite this overlap, the PDAC-associated proteins were notably different compared to chronic pancreatitis. Moreover, the current and previous studies have demonstrated that it is the combination of markers in a multiplexed signature that will deliver the most precise accuracy, regardless of whether a subset of the markers are overlapping with inflammatory or non-related indications.
[0353] Discussion
[0354] For the identification of a plasma marker signature two complementary strategies were initially used, (i) univariate differential expression analysis generating a multiple-testing corrected q-value for each antibody in the assay, and (ii) a backward elimination approach designed to pinpoint the optimal combination of markers, contributing with orthogonal information for discriminating cases and controls (Carlsson et al., 2011a). The two strategies resulted in the identification of a robust core signature of the five proteins Properdin, VEGF, IL-8, C3, and CHP-1. Properdin, or Complement Factor P, was previously identified in two independent studies as strongly down-regulated in both serum (Wingren et al., 2012) and plasma (Gerdtsson et al, unpublished observations), but has apart from that, to the best of our knowledge, not previously been associated with PDAC. In contrast, VEGF, associated with the angiogenesis-dependence of tumor growth, is a known upregulated marker in many cancers including PDAC (Itakura et al., 1997). The VEGF antibody, which specificity has been validated by mass spectrometry, has also in earlier studies demonstrated a significantly elevated VEGF level in PDAC (Gerdtsson, 2015; Wingren et al., 2012). Also IL-8 and Complement Factor C3 have previously been shown to be associated with late stage pancreatic cancer (Chen et al., 2013; Shaw et al., 2014; Wingren et al., 2012). In contrast, CHP-1, Calcineurin Homologous Protein-1, has not previously been measured and we believe its association with PDAC is novel to this study. CHP-1 is part of the Ca.sup.2+-binding family, and is a widely expressed protein localized in multiple subcellular compartments. Apart from being involved in trafficking across the plasma membrane, the functions of this presumably pluripotent protein is largely unknown (Jimenez-Vidal et al., 2010)
[0355] The results showed that the core signature needed to be supplemented with additional proteins in order to achieve the highest possible sensitivity and specificity. Here, approximately 23 markers were shown to deliver an optimal discrimination of PDAC vs. NC. In addition to the 5-protein core, several potential markers of interest were identified. Apo-A1 was one of the strongest differentially expressed proteins, as shown by all three Apo-A1-specific antibodies (q-values 0.003-0.02). Its significant down-regulation in plasma from PDAC patients has previously been seen (Honda et al., 2012) (Gerdtsson et al, unpublished observations). Apo-A1 is the major component of high density lipoprotein (HDL) in plasma and decreased levels of HDL are associated with poor cardiovascular health. Thus the reduced Apo-A1 levels observed in this study may reflect the association of PDAC with smoking and obesity. Another strongly down-regulated marker was Complement Factor C1q, in accordance with our previous study (Wingren et al., 2012). It is noteworthy that although both Apo-A1 and C1q were among the top markers based on univariate analysis, they were not included in the consensus signature derived from the backward elimination analysis, which only takes into account the performance of the combined signature and not the individual markers therein. In contrast, MAPK-8 was identified as a high scoring marker by both approaches. MAPK-8, a serine/threonine protein kinase involved in several cellular processes and signaling pathways, has not previously been analyzed in multiparametric assays and its discriminatory power and role in PDAC needs to be confirmed in future studies. Of note, although the sample subgroups were well age matched the PDAC and NC group had a skewed gender distribution. To investigate if the classifier for PDAC vs. NC was affected by the bias in gender, a gender adjusted dataset was created by an additional ComBat normalization step. The result clearly demonstrated that the list of significant antibodies for PDAC vs. NC in the gender adjusted dataset was highly similar to that of the original dataset. Furthermore, an SVM based analysis also demonstrated that male vs female were poorly separated, as compared to PDAC vs NC, again showing that gender was not a confounding factor for the PDAC vs NC classifiers.
[0356] To the best of our knowledge, this is the first proteomics study identifying stage-specific PDAC markers in plasma. Since early diagnosis significantly increases the life expectancy of PDAC patients (Furukawa et al., 1996; Shimizu et al., 2005), the defined markers associated with stage I/II are of particular importance when designing a clinically relevant test. Although the discrimination of PDAC vs. NC increased with PDAC stage, we were still able to discriminate stage I/II patients from normal individuals. The results are based on using all data from the microarray analysis, but could be condensed to signatures of high power. Several proteins, including AGAP-2, BTK, CDK-2, IL-13, IL-6, MUC-1, PTPRO, USP-7, were shown to have elevated levels in locally confined early stage cancer specifically. Four of these, AGAP-2, CDK-2, PTPRO, and USP7, have not previously been measured in our microarray assay. CDK-2, or Cyclin-dependent kinase 2, is involved in controlling the cell cycle and the aberrant activation of the CDKs is a well-known hallmark of many cancers, including PDAC (Feldmann et al., 2011). The remaining novel markers have not previously been associated with PDAC specifically Other PDAC markers that have been previously identified (Ingvarsson et al., 2008; Wingren et al., 2012), include MUC-1 which is overexpressed in 90% of PDAC cases (Winter et al., 2012), the cytokines IL-6 (Bellone et al., 2006) and IL-13 (Gabitass et al., 2011), as well as the tyrosine kinase BTK.
[0357] The focus of the present study was indeed the identification of stage-specific plasma proteins and the ability to discriminate between resectable pancreatic cancer and disseminated disease. However, differential diagnosis of cancer versus pancreatitis is sometimes difficult and an issue deciphered in a recent study focused in particular on inflammation in pancreas, where we showed that protein signatures could be identified that clearly discriminated between acute, chronic and autoimmune pancreatitis and normal controls (Sandstrom et al., 2012). Importantly, the inflammation associated protein signatures also differed from the Stage I, II, III, IV associated marker signatures in the present study. These findings were further supported by a previous study identifying a signature discriminating between pancreatic cancer patients and a combination of controls, including patients with different inflammatory indications of the pancreas, as well as healthy individuals (Wingren et al., 2012).
[0358] The biological diversity of tumors due to localization in pancreas has been previously demonstrated (Ling et al., 2013). Tumors in the body and tail of pancreas are rarer than tumor in the head of pancreas (77% of PDAC) (Lau et al., 2010). Because of differences in e.g. blood supply and lymphatic and venous backflow, there are also differences in the disease presentation with body and tail tumors causing less jaundice, more pain, higher albumin and CEA levels and lower CA19-9 levels (Eyigor et al., 2010; Watanabe et al., 2004). Body and tail tumors are more often detected at a late stage than head tumors and have a higher rate of metastasis. As the biological variances can result in different treatment efficiency (Wu et al., 2007), markers that can discriminate between tumor localization would be of clinical relevance and could aid personalized treatment strategies. However, few differences have been found on a genetic level, with no significant variation in the overall number of mutations, deletions and amplifications, or in K-ras point mutations (Ling et al., 2013). Here, 37 antibodies identified markers that showed on differential protein expression levels between head and body/tail tumors, and this expression pattern correlated remarkably well with a previous study. Consequently, these results are encouraging for a future development of a blood protein biomarker signature discriminating body/tail and head tumors at an early disease stage.
[0359] Ethnic genetic diversity is well described and is, in addition to environmental factors, coupled to e.g. the incidence and progression of cancer in different parts of the world (Gupta et al., 2014; Rastogi et al., 2004). On the contrary, we here show that PDAC patients of Asian and Caucasian origin express similar disease-associated protein signatures. While biological heterogeneity is indeed a hurdle in the search for genetic biomarkers (Gupta et al., 2014), our findings indicate that proteomic biomarkers may be more robust and transferrable between different ethnicities, due to less diversity on a whole protein level as compared to genetic mutations.
[0360] In summary, we have demonstrated that resectable pancreatic cancer (stage I/II) as well as locally advanced (stage III) and distant metastatic (stage IV) disease could for the first time be accurately discriminated, a prerequisite for a test focusing on early diagnosis of pancreatic cancer. Furthermore, we provide information that plasma protein markers associated with different tumor locations in the pancreas could be identified.
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TABLE-US-00001 TABLE A 1-4 1 2 1 + 2 # Short name Accession # vs HC vs HC vs HC vs HC (I) - Preferred 1/2/1 + 2 1 R-PTP-O Q16827 ↑ ↑ ↑ 2 UBP7 Q93009 ↑ ↑ ↑ ↑ 3 CHP-1 Q99653 ↑ ↑ ↑ ↑ 4 MAPKK 2 P36507 ↓ ↓ ↓ ↓ 5 MAPKK 6 P52564 ↑ ↑ ↑ (II) - Optional 1/2/1 + 2 6 Apo-A1 P02647 ↓ ↓ ↓ ↓ 7 BTK Q06187 ↑ ↑↓ ↑ ↑ 8 C1q P02745/6/7 ↓ ↓ ↓ ↓ 9 C3 P01024 ↓ ↓ ↓ ↓ 10 C5 P01031 ↑ ↑↓ ↑ ↑ 11 CDK-2 P24941 ↑ ↑ ↑ ↑ 12 IgM P01871 ↓ ↓ ↓ ↓ 13 IL-11 P20809 ↑ ↑ ↑ ↑ 14 IL-12 P29459/60 ↑ ↑ ↑ ↑ 15 IL-6 P05231 ↑↓ ↑ ↑ ↑ 16 JAK3 P52333 ↑ ↑ ↑ ↑ 17 MAPK8 P45983 ↑ ↑ ↑ ↑ 18 MCP-1 P13500 ↑↓ ↑ ↑ ↑ 19 MUC-1 P15941 ↑ ↑ ↑ ↑ 20 Properdin P27918 ↓ ↓ ↓ ↓ 21 VEGF P15692 ↑ ↑ ↑ ↑ (III) - Preferred 1/1 + 2 22 PRD14 Q9GZV8 ↑ ↑ ↑ 23 GRIP-2 Q9C0E4 ↑ ↑ 24 MAPK9 P45984 ↑ ↑ 25 PKB gamma Q9Y243 ↑ ↑ (AKT-3) 26 R-PTP-eta Q12913 ↑↓ ↑ 27 TopBP1 Q92547 ↑ ↑↓ (IV) - Optional 1/1 + 2 28 CD40L P29965 ↑ ↑ 29 EGFR P00533 ↑ ↑ 30 HADH2 Q6IBS9 ↑ ↑ 31 ICAM-1 P05362 ↑↓ ↑↓ ↑↓ 32 IL-13 P35225 ↑↓ ↑ ↑ 33 IL-18 Q14116 ↑ ↑ 34 MYOM2 P54296 ↓ ↓ 35 Osteopontin P10451 ↑ ↑ 36 P85A P27986 ↑↓ ↑↓ 37 RANTES P13501 ↑ ↑ 38 TGF-b1 P01137 ↑ ↑ 39 IL-4 P05112 ↑ ↑ (V) - Preferred 2/1 + 2 40 CIMS (13) SSAYSR* ↑ ↑ 41 GNAI3 P08754 ↑ ↑ 42 HsMAD2 Q13257 ↑ ↑ 43 hSpindly Q96EA4 ↑ ↑ 44 R-PTP-kappa Q15262 ↑↓ ↑↓ 45 STAT1 P42224 ↑↓ ↑ ↑ (VI) - Optional 2/1 + 2 46 ATP-5B P06576 ↑ ↑ ↑ 47 C4 P0COL4/5 ↓ ↓ ↓ 48 CHX10 P58304 ↑ ↑ 49 Factor B P00751 ↓ ↓ 50 Her2/ErbB-2 P04626 ↑ ↑ ↑ 51 IL-1b P01584 ↑↓ ↑↓ 52 IL-7 P13232 ↑↓ ↑ ↑ 53 IL-10 P22301 ↑ ↑ 54 Lewis X NA ↑ ↑ 55 MCP-3 P80098 ↑ ↑ 56 Sialyl Lewis x NA ↑ ↑ 57 TBC1D9 Q6ZT07 ↑ ↑ 58 TNFRSF3 P36941 ↑ ↑ (VII) - Preferred 1 59 AGAP-2 Q99490 ↑↓ ↑ (VIII) - Optional 1 60 C1-INH P05155 ↑ 61 C1s P09871 ↑↓ 62 GLP-1 R P43220 ↑↓ ↑ 63 IL-2 P60568 ↑↓ 64 KSYK P43405 ↑ 65 MAPK1 P28482 ↑ (IX) - Preferred 2 66 TENS4 Q8IZW8 ↑ (X) - Optional 2 67 FASN Q6PJJ3 ↑↓ 68 IL-3 P08700 ↑↓ ↑↓ 69 IL-8 P10145 ↓ ↑↓ 70 STAP2 Q9UGK3 ↑↓ (XI) - Preferred 1 + 2 71 HsHec1 O14777 ↑ 72 PAR-6B Q9BYG5 ↑ 73 PGAM5 Q96HS1 ↑ ↑ (XII) - Optional 1 + 2 74 IFN-γ P01579 ↑ 75 IL-16 Q14005 ↑ 76 Sox11A P35716 ↑ 77 TNF-b P01374 ↑ 78 TNFRSF14 Q92956 ↑ 79 UPF3B Q9BZI7 ↑ (XIII) - Preferred 1-4 80 LUM P51884 ↑↓ 81 PTPRO Q16827 ↑↓ (XIV) - Optional 1-4 82 GM-CSF P04141 ↑ 83 IL-9 P15248 ↑↓ 84 LDL P04114 ↑↓ 85 ORP-3 Q9H4L5 ↑↓ *peptide antibody was selected against, not database accession number. ‘↑’ indicates the biomarker is up-regulated in PC; ‘↓’ indicates the biomarker is down-regulated in PC; ‘↑↓’ indicates the biomarker is dysregulated in PC, but the trend may be up- or down-regulation (i.e., the biomarker is up-regulated in some PC subtype(s), down-regulated in others, and/or non-dysregulated yet others);
TABLE-US-00002 TABLE 1 Clinical samples No of Gender Median age Group samples (M/F) (range) Tumor location Stage grouping* PDAC 118 76/42 59 (21-83) Head = 69, Body/Tail = 39 Stage I 11 6/5 59 (48-71) Head = 6, Body/Tail = T1/2, N0, M0 Stage II 33 16/17 59 (46-83) Head = 27, Body/Tail = 6 T1-3, N0/1, M0 Head = 22, Body/Tail = 12, Stage III 38 28/10 59 (21-75) Neck/Neck + Body = 4 T4, any N, M0 Stage IV 36 26/10 59 (38-75) Head = 14, Body/Tail = 20, Any T & N, M1 Neck/Head + Tail = 2 NC 95 20/75 63 (52-74) N/A Total 213 96/117 62 (21-83) *Staging according to the guidelines of the American Cancer Society
TABLE-US-00003 TABLE 2 Top 25 signature candidate analytes Previous Median Benjamini- elimination Elimination elimination Wilcoxon Hochberg Wilcoxon Fold rank (Wingren rank Name score p-value q-value rank change et al., 2012) 1 Properdin 1 6.18E−15 2.08E−12 1 0.74 3 2 VEGF (3) 2 1.84E−08 3.10E−06 2 1.25 17 3 IL-8 (3) 11.5 1.99E−03 6.07E−02 11 0.87 114 4 C3 (4) 12.5 3.74E−05 3.15E−03 4 0.83 N/A 5 CHP-1 (2) 13 4.47E−06 5.00E−04 3 1.16 N/A 6 C3 (3) 17 1.31E−01 6.01E−01 72 1.08 N/A 7 MAPK-8 (3) 19.5 1.85E−04 7.76E−03 8 1.22 N/A 8 MCP-1 (6) 19.5 1.32E−01 6.01E−01 74 0.96 N/A 9 IL-7 (2) 23 2.53E−01 7.60E−01 111 1.03 21 10 C4 (3) 23.5 2.96E−03 8.29E−02 12 0.89 N/A 11 IgM (5) 24.5 5.61E−05 3.77E−03 5 0.92 N/A 12 IL-3 (1) 27 7.36E−02 5.72E−01 40 1.06 18 13 IL-11 (3) 28 2.17E−02 3.03E−01 24 1.08 35 14 C5 (2) 31 1.81E−02 2.84E−01 21 1.09 1 15 IL-6 (6) 32 4.95E−01 8.88E−01 187 0.97 N/A 16 C3 (6) 35 6.06E−02 5.66E−01 36 1.09 N/A 17 ICAM-1 37 7.36E−01 9.37E−01 263 1.01 N/A 18 MCP-1 (1) 38.5 1.22E−01 5.89E−01 69 1.04 15 19 LDL (1) 39.5 2.33E−01 7.52E−01 104 1.02 N/A 20 JAK3 42 1.96E−02 2.86E−01 23 1.05 34 21 MAPK-8 (2) 43 6.79E−02 5.72E−01 38 1.07 N/A 22 MUC-1 (5) 44.5 1.02E−02 2.29E−01 15 1.09 53 23 BTK (3) 44.5 2.06E−01 7.26E−01 93 1.03 N/A 24 IL-7 (1) 45 1.61E−01 6.61E−01 82 0.97 88 25 LUM 46.5 1.04E−01 5.89E−01 55 1.05 N/A
TABLE-US-00004 TABLE 3 Antibodies included on the array Antigen Full name No of scFvs AGAP-2 Arf-GAP with GTPase, ANK repeat and PH-dom.-containing 4 protein 2 Apo-A1 Apolipoprotein A1 3 Apo-A4 Apolipoprotein A4 3 ATP-5B ATP synthase subunit beta 3 BTK Tyrosine-protein kinase BTK 4 C1 inh. C1 esterase inhibitor 4 C1q* Complement C1q 1 C1s Complement C1s 1 C3* Complement C3 6 C4* Complement C4 4 C5* Complement C5 3 CD40 CD40 protein 4 CD40L CD40 ligand 1 CDK-2 Cyclin-dependent kinase 2 2 CHP-1 Calcineurin B homologous protein 1 2 CHX-10 Visual system homeobox 2 3 CIMS-10 Selection motif TEEQLK 1 CIMS-13 Selection motif SSAYSR 1 CIMS-5 Selection motif WTRNSNMNYWLIIRL 1 CK19 Cytokeratin 19 3 CT17 Cholera toxin subunit B 1 CystC Cystatin C 4 Digoxin Digoxin 1 DUSP-9 Dual specificity protein phosphatase 9 1 EGFR Epidermal growth factor receptor 1 Eotaxin Eotaxin 3 ErbB-2 Receptor tyrosine-protein kinase erbB-2 4 Factor B* Complement factor B 4 FASN Fatty acid synthase 4 GAK Cyclin G-associated kinase 3 GEM GTP-binding protein GEM 2 GLP-1 Glucagon-like peptide-1 1 GM-CSF Granulocyte-macrophage colony-stimulating factor 6 GNAI-3 Guanine nucleotide-binding protein G(k) subunit alpha 4 GRIP-2 Glutamate receptor-interacting protein 2 8 HADH-2 3-hydroxyacyl-CoA dehydrogenase type-2 4 HLA-DR/DP HLA-DR/DP 1 ICAM-1 Intercellular adhesion molecule 1 1 IFN-g Interferon gamma 3 IgM Immunoglobulin M 5 IL-10* Interleukin 10 3 IL-11 Interleukin 11 3 IL-12* Interleukin 12 4 IL-13* Interleukin 13 3 IL-16 Interleukin 16 3 IL-18 Interleukin 18 3 IL-1a* Interleukin 1 alpha 3 IL-1b Interleukin 1 beta 3 IL-1ra Interleukin-1 receptor antagonist protein 3 IL-2 Interleukin 2 3 IL-3 Interleukin 3 3 IL-4* Interleukin 4 4 IL-5* Interleukin 5 3 IL-6* Interleukin 6 4 IL-7 Interleukin 7 2 IL-8* Interleukin 8 3 IL-9 Interleukin 9 3 Integrin a-10 Integrin alpha-10 1 Integrin a-11 Integrin alpha-11 1 JAK3 Tyrosine-protein kinase JAK3 1 KRAS GTPase KRas 1 KSYK Tyrosine-protein kinase SYK 2 LDL Low-density Lipoprotein 2 Leptin Leptin 1 Lewis x Lewis x 2 Lewis y Lewis y 1 LUM Lumican 1 MAD2L-1 Mitotic arrest deficient 2-like protein 1 3 MAP2K-2 Mitogen-activated protein kinase kinase 2 3 MAP2K-6 Mitogen-activated protein kinase kinase 6 4 MAPK-1 Mitogen-activated protein kinase 1 4 MAPK-8 Mitogen-activated protein kinase 8 3 MAPK-9 Mitogen-activated protein kinase 9 6 MATK Megakaryocyte-associated tyrosine-protein kinase 3 MCP-1* Monocyte chemotactic protein 1 9 MCP-3 Monocyte chemotactic protein 3 7 MCP-4 Monocyte chemotactic protein 4 3 MUC-1 Mucin 1 6 Myom-2 Myomesin-2 2 NDC80 Kinetochore protein NDC80 homolog 3 ORP-3 Oxysterol-binding protein-related protein 3 2 OSTP Osteopontin 3 P85A PI3-kinase subunit p85-alpha 3 PAK-7 Serine/threonine-protein kinase PAK 7 3 PAR-6B Partitioning defective 6 homolog beta 2 PARP-1 Poly [ADP-ribose] polymerase 1 1 PGAM-5 Phosphoglycerate mutase family member 5 4 PKB gamma RAC-gamma serine/theonine-protein kinase 2 PRD-14 PR domain zinc finger protein 14 5 Procath W Procathepsin W 1 Properdin* Properdin 1 PSA Prostate-specific antigen 1 PTK-6 Protein-tyrosine kinase 6 1 PTPN-1 Tyrosine-protein phosphatase non-receptor type 1 3 PTPRJ Protein-tyrosine phosphatase receptor type J 8 PTPRK Protein-tyrosine phosphatase kappa 8 PTPRO Protein-tyrosine phosphatase U2 4 PTPRT Protein-tyrosine phosphatase rho 3 RANTES RANTES 3 RPS6KA2 Ribosomal protein S6 kinase alpha-2 3 Sialle x Sialyl Lewis x 1 Sox11A Transcription factor SOX-11 1 SPDLY-1 Spindly 2 STAP-2 Signal-transducing adaptor protein 2 4 STAT-1 Signal transducer and activator of transcription 1-alpha/beta 2 TBC1D-9 TBC1 domain family member 9 3 TENS-4 Tensin 4 1 TGF-b1 Transforming growth factor beta-1 3 TM peptide Transmembrane peptide 1 TNF-a Tumor necrosis factor 3 TNF-b* Lymphotoxin-alpha 4 TNFRSF-14 Tumor necrosis factor receptor superfamily member 14 2 TNFRSF-3 Tumor necrosis factor receptor superfamily member 3 3 TOPBP-1 DNA topoisomerase 2-binding protein 1 2 UBC-9 Ubiquitin carrier protein 9 3 UBE2C Ubiquitin-conjugating enzyme E2 C 2 UCHL5 Ubiquitin carboxyl-terminal hydrolase isozyme L5 1 UPF3B Regulator of nonsense transcripts 3B 2 USP-7 Ubiquitin-specific-processing protease 7 4 VEGF* Vascular endothelial growth factor 4 *Specificity determined by protein arrays, cytokine arrays, ELISA, blocking/spiking experiments and/or mass spectrometry.
TABLE-US-00005 TABLE 4 comparison of significant (Wilcoxon p < 0.05) markers cancer vs non-cancer all data cancer vs non-cancer gender-adjusted data PDAC (108) vs NC (94) ROC area: 0.88 PDAC (108) vs NC (94) ROC area: 0.89 Fold Wilcoxon BH Fold Wilcoxon BH Name change p-value q-value Name change p-value q-value Properdin 0.741 6.18E−15 2.08E−12 Properdin 0.753 5.17E−14 1.74E−11 VEGF 1.252 1.84E−08 3.10E−06 VEGF 1.267 4.36E−09 7.33E−07 CBPP22 1.164 4.47E−06 0.00050 IgM 0.912 3.30E−06 0.00030 C3 0.830 3.74E−05 0.00315 C3 0.815 3.62E−06 0.00030 IgM 0.924 5.61E−05 0.00377 CBPP22 1.154 1.16E−05 0.00078 C1q 0.889 0.000129 0.00644 C1q 0.881 3.99E−05 0.00223 MK08 1.218 0.000185 0.00776 ApoA1 0.899 9.03E−05 0.00434 ApoA1 0.885 0.000432 0.01615 MK08 1.219 0.000142 0.00531 IL-B 0.874 0.001986 0.06066 BTK 1.083 0.000278 0.00933 C4 0.888 0.002962 0.08293 UBP7 1.101 0.000398 0.01178 Her2 1.058 0.006326 0.16351 Her2 1.078 0.000465 0.01202 MAP2K2 0.939 0.007056 0.16935 MUC1 1.110 0.000659 0.01582 MUC1 1.086 0.010208 0.22866 PRD14 1.074 0.000993 0.02225 UBP7 1.078 0.011248 0.23620 JAK3 1.074 0.001081 0.02271 C5 1.059 0.012983 0.25660 MCP-3 1.083 0.001672 0.03305 CDK2 1.072 0.014557 0.27173 TNFRSF3 1.060 0.001922 0.03447 ATPSB 1.060 0.015457 0.27334 MAP2K6 1.079 0.002002 0.03447 PGAM5 1.071 0.016622 0.27926 PGAM5 1.093 0.002051 0.03447 MAP2K6 1.109 0.018576 0.28371 MAPK9 1.100 0.002189 0.03502 JAK3 1.053 0.019563 0.28579 MCP1 1.107 0.002610 0.03863 IL-11 1.079 0.021675 0.30345 MAP2K2 0.933 0.002694 0.03863 PRD14 1.049 0.031840 0.41147 STAT1 1.073 0.002759 0.03863 IL-12 1.069 0.039907 0.47888 C4 0.888 0.003080 0.04139 BTK 1.050 0.048259 0.54050 C5 1.071 0.003203 0.04139 CSF2 1.039 0.048259 0.54050 PTPRJ 1.080 0.003330 0.04144
TABLE-US-00006 TABLE 5 apriori <− read.delim(“apri.txt”,header=FALSE) apriori <− as.character(apriori[[1]]) aprioriBoolean <− is.element(rownames(data) , apriori) filnamn<−“Stages I+II.txt” rawfile <− read.delim(filnamn) samplenames <− as.character(rawfile[,1]) groups <− rawfile[,2] data <− t(rawfile[,-c(1:2)]) ProteinNames <− read.delim(filnamn,header=FALSE) ProteinNames <− as.character(as.matrix(ProteinNames)[1,]) ProteinNames <− ProteinNames[-(1:2)] rownames(data) <− ProteinNames colnames(data) <− samplenames library(MASS) library(gplots) library(e1071) source(“NaiveBayesian”) redgreen <− function(n) { c( hsv(h=0/6, v=c( rep( seq(1,0.3,length=5) , c(13,10,8,6,4) ) , 0 ) ) , hsv(h=2/6, v=c( 0 , rep( seq(0.3,1,length=5) , c(3,5,7,9,11) ) ) ) ) } pal <− rev(redgreen(100)); svmLOOvalues <− function(data , fac){ n1 <− sum(fac==levels(fac)[1]) n2 <− sum(fac==levels(fac)[2]) nsamples <− n1+n2 ngenes <− nrow(data) SampleInformation <− paste(levels(fac)[1],“ ”,n1,“ , ”, levels(fac)[2],“ ”,n2,sep=“”) res <− numeric(nsamples) sign <− numeric(nsamples) for (i in 1:nsamples){ svmtrain <− svm(t(data[,−i]) , fac[−i] , kernel=“linear” ) pred <− predict(svmtrain , t(data[,i]) , decision.values=TRUE) res[i] <− as.numeric(attributes(pred)$decision.values) facnames <− colnames(attributes(pred)$decision.values)[1] if (facnames == paste(levels(fac)[1],“/”,levels(fac)[2],sep=“”)){sign[i] <− 1} if (facnames == paste(levels(fac)[2],“/”,levels(fac)[1],sep=“”)){sign[i] <− −1} } if (length(unique(sign)) >1){print(“error”)} res <− sign * res names <− colnames(data , do.NULL=FALSE) orden <− order(res , decreasing=TRUE) Samples <− data.frame(names[orden],res[orden],fac[orden]) ROCdata <− myROC(res,fac) SenSpe <− SensitivitySpecificity(res,fac) return(list(SampleInformation=SampleInformation, ROCarea=ROCdata[1],p.val ue=ROCdata[2],SenSpe <− SenSpe,samples=Samples)) } wilcoxtest <− function(prot,subset1,subset2){ res <− wilcox.test(prot[subset1],prot[subset2]) res$p.value } # Definierar foldchange foldchange <− function(prot,subset1,subset2){ 2{circumflex over ( )}(mean(prot[subset1]) − mean(prot[subset2])) } # Definierar q-värdesberäkningen BenjaminiHochberg <− function(pvalues){ # This function takes a vector of p-values as input and outputs # their q-values. No reordering of the values is performed NAindices <− is.na(pvalues) Aindices <− !NAindices Apvalues <− pvalues[Aindices] N <− length(Apvalues) orderedindices <− order(Apvalues) OrdValues <− Apvalues[orderedindices] CorrectedValues <− OrdValues * N /(1:N) MinValues <− CorrectedValues for (i in 1:N){MinValues[i] <− min(CorrectedValues[i:N])} Aqvalues <− numeric(N) Aqvalues[orderedindices] <− MinValues Qvalues <− pvalues Qvalues[Aindices] <− Aqvalues return(Qvalues) } AnalyseraMAA <− function(group1 ,group2){ outputfiletxt <− paste(group1,“ versus ”,group2,“.txt” ,sep=“”) outputfilepdf <− paste(group1,“ versus ”,group2,“.pdf” , sep=“”) subset1 <− is.element(groups , strsplit(group1,“,”)[[1]]) subset2 <− is.element(groups , strsplit(group2,“,”)[[1]]) wilcoxpvalues <− apply(data , 1 , wilcoxtest , subset1 , subset2) foldchange <− apply(data , 1 , foldchange , subset1 , subset2) QvaluesAll <− BenjaminiHochberg(wilcoxpvalues) QvaluesApriori <− numeric(length(wilcoxpvalues)) QvaluesApriori[!aprioriBoolean] <− NA QvaluesApriori[aprioriBoolean] <− BenjaminiHochberg(wilcoxpvalues[aprioriBoolean]) HugeTable <− cbind(ProteinNames,foldchange,wilcoxpvalues,QvaluesAll, QvaluesApriori) write.table(HugeTable, file=outputfiletxt , quote=FALSE, sep=“\t”,row.names=FALSE) color <− rep(‘black’ , length(subset1)) color[subset1] <− ‘red’ color[subset2] <− ‘blue’ pdf(outputfilepdf) Sam <− sammon(dist(t(data[,subset1|subset2])) , k=2) plot(Sam$points , type=“n” , xlab = NA , ylab=NA, main= “All proteins”,asp=1) text(Sam$point , labels = colnames(data[,subset1|subset2]), col=color[subset1|subset2]) Sam <− sammon(dist(t(data[aprioriBoolean,subset1| subset2])) , k=2) plot(Sam$points , type=“n” , xlab = NA , ylab=NA, main=“Aprioriproteins” ,asp=1) text(Sam$point , labels = colnames(data[,subset1|subset2]), col=color[subset1|subset2]) heatmap.2(data[,subset1|subset2] , labRow = row.names(data), trace=“none” , labCol =“” , ColSideColors= color[subset1|subset2],col=pal , na.color= “grey”, key=FALSE , symkey=FALSE , tracecol = “black” , main =“” , dendrogram= ‘both’ , scale =“row” ,cexRow=0.2) heatmap.2(data[apriori,subset1|subset2] , labRow = row.names(data[apriori,subset1|subset2]), trace=“none” , labCol =“” , ColSideColors= color[subset1|subset2],col=pal , na.color= “grey”, key=FALSE , symkey =FALSE , tracecol = “black” , main =“” , dendrogram=‘both’ , scale =“row”) svmfac <− factor(rep(‘rest’,ncol(data)),levels=c(group1,group2,‘rest’)) svmfac[subset1] <− group1 svmfac[subset2] <− group2 svmResAll <− svmLOOvalues(data[,subset1|subset2] , factor(as.character(svmfac[subset1|subset2]),levels= c(group1,group2))) svmResApriori <− svmLOOvalues(data[apriori, subset1|subset2] , factor(as.character(svmfac[subset1|subset2]),levels=c(group1, group2))) ROCplot(svmResAll , sensspecnumber=4) ROCplot(svmResApriori , sensspecnumber=4) write(“” , file=outputfiletxt , append=TRUE) write(“All proteins” , file=outputfiletxt , append=TRUE) write(“” , file=outputfiletxt , append=TRUE) for (i in 1:5){write.table(svmResAll[[i]], file=outputfiletxt , append=TRUE, sep=“\t” , quote=FALSE) write( “” , file=outputfiletxt , append=TRUE) } write(“” , file=outputfiletxt , append=TRUE) write(“Apriori proteins” , file=outputfiletxt , append=TRUE) write(“” , file=outputfiletxt , append=TRUE) for (i in 1:5){write.table(svmResApriori[[i]], file=outputfiletxt , append=TRUE, sep=“\t” , quote=FALSE) write( “” , file=outputfiletxt , append=TRUE) } dev.off( ) } AnalyseraMAA(“I+II”,“non-cancer”)
TABLE-US-00007 TABLE 6 ROC-AUCs for (example signature 1) Order of Uniprot Publication Signature ROC- elimination smallestErrorPerLength Antibody entry ID Full antigen name name length AUC 336 NA Prop-3 P27918 Properdin Properdin 1 NA 335 68.227384 VEGF-3 P15692 Vascular endothelial growth factor VEGF (3) 2 0.84 334 56.359648 C1q-4 P02745/6/7 Complement C1q C1q 3 0.89 333 52.20471 IL-11-45 P20809 Interleukin-11 IL-11 (3) 4 0.89 332 50.36022 JAK3 P52333 Tyrosine-protein kinase JAK3 JAK3 5 0.89 331 47.573241 ICAM-1 P05362 Intercellular adhesion molecule 1 ICAM-1 6 0.92 330 48.842061 IL-12-39 P29459/60 Interleukin-12 IL-12 (1) 7 0.91 329 45.823312 C-AKT3-1 Q9Y243 RAC-gamma serine/threonine-protein PKB gamma 8 0.92 kinase (1) 328 45.489121 C5-9 P01031 Complement C5 C5 (2) 9 0.94 327 47.220274 C3_016_D12 P01024 Complement C3 C3 (4) 10 0.92 326 39.899609 C-P85A-2 P27986 Phosphatidylinositol 3-kinase regulatory P85A (1) 11 0.95 subunit alpha 325 36.255768 IL-6-58 P05231 Interleukin-6 IL-6 (2) 12 0.96 324 34.457063 I-PTPRK-15 Q15262 Receptor-type tyrosine-protein R-PTP-kappa 13 0.96 phosphatase kappa (2) 323 28.625926 I-MAP2K6-3 P52564 Dual specificity mitogen-activated protein MAPKK 6 (2) 14 0.98 kinase kinase 6 322 28.699206 I-TOPB1-1 Q92547 DNA topoisomerase 2-binding protein 1 TopBP1 (1) 15 0.98 321 26.57558 I-PGAM5-2 Q96HS1 Serine/threonine-protein phosphatase PGAM5 (2) 16 0.99 PGAM5, mitochondrial 320 24.772185 I-CBPP22-3 Q99653 Calcineurin B homologous protein 1 CHP1 (2) 17 0.99 319 24.58218 P3-16 P15941 Mucin-1 MUC1 (5) 18 0.99 318 22.865319 IgM-3 N/A N/A IgM (3) 19 0.99 Signatures accumulate according to the order shown, e.g., the signature with three analytes comprises properdin, VEGF and C1q.
TABLE-US-00008 TABLE 7 ROC-AUCs for (example signature 2) Uniprot Publication Fold Wilcoxon Signature ROC- Priority Analyte Antibody entry ID name change p-value Q-value length AUC core 1 R-PTP-O I-PTPRO-4 Q16827 R-PTP-O (2) 1.070125572 0.009704244 0.098806849 1 0.64 core 2 UBP7 I-UBP7-10 Q93009 UBP7 (1) 1.11356247 0.002987912 0.055774355 2 0.51 3 PRD14 I-PRD14-1 Q9GZV8 PRD14 (1) 1.076408781 0.039871393 0.155799707 3 0.41 4 GRIP-2 I-GRIP2-5 Q9C0E4 GRIP-2 (5) 1.106919962 0.023770038 0.137702289 4 0.59 5 CHP-1 I-CBPP22-3 Q99653 CHP1 (2) 1.161203653 0.00065158 0.019911196 5 0.73 6 MAPKK 2 I-MAP2K2-5 P36507 MAPKK 2 (2) 0.904776087 0.002285971 0.048005396 6 0.69 7 MAPKK 6 I-MAP2K6-4 P52564 MAPKK 6 (3) 1.157809175 0.011922794 0.111279406 7 0.72 8 R-PTP-eta I-PTPRJ-1 Q12913 R-PTP-eta (1) 1.09949869 0.017976981 0.13018673 8 0.71 9 TopBP1 I-TOPB1-2 Q92547 TopBP1 (2) 1.071204183 0.112701484 0.268565239 9 0.73 10 MAPK9 I-MAPK9-5 P45984 MAPK9 (4) 1.107889922 0.007750485 0.086805429 10 0.69 11 PKB gamma C-AKT3-1 Q9Y243 PKB gamma (1) 1.061977425 0.048411664 0.171224411 11 0.68 12 CIMS (13) FN17-C08 N/A CIMS (13) 1.10417223 0.00563986 0.073961513 12 0.74 13 GNAI3 I-GNAI3-6 P08754 GNAI3 (3) 1.090520613 0.011137803 0.110067699 13 0.72 14 HsMAD2 I-MD2L1-7 Q13257 HsMAD2 (3) 1.10784704 0.03423597 0.152971314 14 0.72 15 hSpindly I-SPDLY-2 Q96EA4 hSpindly (2) 1.076228973 0.006156874 0.076618872 15 0.72 16 R-PTP-kappa I-PTPRK-8 Q15262 R-PTP-kappa (7) 1.074997443 0.182672471 0.350731144 16 0.73 17 STAT1 C-STAT1-3 P42224 STAT1 (2) 1.081796782 0.015781058 0.129327692 17 0.79 18 HsHec1 I-NDC80-3 O14777 HsHec1 (2) 1.075526742 0.040804685 0.155799707 18 0.78 19 PAR-6B I-PARP6B-2 Q9BYG5 PAR-6B (1) 1.099340103 0.017976981 0.13018673 19 0.77 20 PGAM5 I-PGAM5-2 Q96HS1 PGAM5 (2) 1.095269092 0.03187375 0.152971314 20 0.73 21 AGAP-2 I-CENTG1-1 Q99490 AGAP-2 (1) 1.096662882 0.050068011 0.175238039 21 0.71 22 TENS4 C-TENS4-1 Q8IZW8 TENS4 1.062769906 0.051771605 0.175709691 22 0.75 23 LUM LUM_1 P51884 LUM 1.068518726 0.072383465 0.209662449 23 0.72 24 USP-7 I-UBP7-10 Q93009 UBP7 (1) 1.11356247 0.002987912 0.055774355 24 0.72 Signatures accumulate according to the order shown, e.g., the signature with three analytes comprises R-PTP-O, UBP7 and PRD14.
TABLE-US-00009 TABLE 8 Amino acid sequences of the scFv antibodies used in the Examples Ab Full protein Sequence (VH-linker-VL-tag) IL-1a EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSGYYSWAFDIWGQGTLVTVSSGGGGSGGGGSGG (1) GGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGRNTVNWYQQLPGTAPKLLIYGNSNRPSXVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLNGWAFGGXTKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 1] IL-1a EVQLLLESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVALISYDGSQKYYADSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGHTSGTKAYYFDSWGQGTLVTVSSGGGGSGGGG (2) SGGGGSQSVLTQPPSASGTPGQRVTISCTGTSSNIGAGYSVEIWYCIQLPGTAPMINGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCQSYDSSLSGWVFGGXTKLTVLGEQKLISEEDLSGSAA [SEQ ID NO: 2] IL-2 EVQLLESGGGLVQPGGLRLSCAASGFTFGDYAMSWVRQAPGKGLEWVSSISSRGSYIYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKKKIGYYGLDAWGQGTIATIVSSGGGESGGGGSGGGG (1) SQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPIKLINGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSSYAGSNNLVEGGXTKLTXLGEQKLISXXDLSGSAA [SEQ ID NO: 3] IL-2 EVXXLESGGGLVQPGGSLRLSCAASGFTFGDYAMSWVRQAPGKGLEWVSSISSRGSYIYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKKKTGYYGLDAWGQGTLVTVSSGGGGSGGGGSGGGG (2) SQSVLTQPPSASETPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSSYAGSNNLVFGGXXKLTVLGEQKLISEXXLSGSAA [SEQ ID NO: 4] IL-2 EVQLLESGGGLVQPGGGSLRLSCAASGFTFGDYAMSWVRQAPGKGLEWVSSISSRGSYIYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKKKTGYYGLDAWGQGTLVTVSSGGGGSGGGGSGG (3) GGSQSVLTQPPSASGTPGQRVTISCTGSSSXIGAGYDVHWYQQLPGTAPKLLIYGNSNRP [SEQ ID NO: 5] IL-3 EVQLLESGGGLVQPGGSLRLSCAASGFTFGRYTMHWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVWCARHFEESSGGYFDYWGQGTLVTVSSGGGGSGGGGSGG (1) QGGSQSVLTIRPRSASGTPGRVTISCSGSSSNIGSNTVNWYQQLPGTAPKWYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLNGWVFGGXXKLIVLGEQKLISXXXLSGXAA [SEQ ID NO: 6] IL-3 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGARYDYWGQGTINTVSSGGGGSGGGGSGGGGSQ (2) SVETQPRSASGTPGQRVTISCSGSSSNIGSNTVNWYCZIRLPGTAPKWYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDNILRGVVFGGGTKLTVLXEQKLISEXDLSGSAA [SEQ ID NO: 7] IL-3 EVXXXESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGRGEYTYYAGSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCATGATREGYWGQGTLVTVSSGGGGSGGGGSGGGGSQ (3) SVLTQPPSASGTPGQRVTISCTQSSSNIGAGYGVQWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSXSLAISGLRSEDEADYYCQSYDSSLSYSVFGGXTKLTVLGEQKLISXXDLSGSAA [SEQ ID NO: 8] IL-4 EVQLLESGGGLVQPGGSLRLSCAASGFIFSNAWMSVVVRQAPGKGLEWVSSLEIGGGDTFYTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASLYGSGSYYYYYYGMDVWGQGTLVTVSSGGGGSG (1) GGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGNNSNTGNNAVNIWYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCCSYAGSYIWVEGGXTKLTVLGEQKLISXEXLSG SAA [SEQ ID NO: 9] IL-4 EVQLLESGGGLVQPGGSLRLSCAASGFTESDYGMFIWAIRQAPGKGLEWVSGISWNGGKTHYVDSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRGYCSNGVCYTILDYWECIEILVTVSSGGGG (2) SGGGGSGGGGSQSVLIQPPSASGTGQRVTISCSGSSSNIGSNTINWYQQLPQTAPKWYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGWVFGGXTKLXVLXEQKLISXXDLSGS AA [SEQ ID NO: 10] IL-5 EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMSWVRQAPGKGLEWVSSISSRSNYIYYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNFRFFDKWGQGTLVTVSSGGGGSGGGGSGGGGSQ (1) SVLTQPPSASGTPGQRVIISCSGGSSXIGANPVSWYQQLPGTAPKLLIYGNSNRP [SEQ ID NO: 11] IL-5 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSSISSRSNYIYYSDSVIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNFREEDKWGQGTLVTVSSGGGGSGGGGSGGGGS (2) QSVLTQPPSASGTPGQRVIISCSGGSSXIGANPVSWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGISASLAISGERSEDEADYYCQSYDSSLSGSVFGGXTKLTVLXEQKLISEXXLSGSAA [SEQ ID NO: 12] IL-5 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAIVISWVRQAPGKGLEWVSSISSRSNYIYYSDSVKGRTISRDNSKNTLYLQMNSLRAEDTAVYYCARNFREEDKWGQGTLVIVSSGGGGSGGGGSGGGGS (3) QSVLTQPPSASGTPGQRVIISCSGGSSNIGANPVSWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGSVFGGXTKLTVLGEQKLISXEDLSGSAA [SEQ ID NO: 13] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVWCARNRGSSLYYGMDVWGQGTLVTVSSGGGGSGGGGSGG (1) GGSQSVLTQPPSASGTPGQRVTISCAGSSSNIGSKSVHWYQQLPGTAPKLLIYRNNRRPSGVPDRFSGSXSGTSXSLAIXGLRSXDXADYYCXXWDDRVNXXXFGGXTXLTVLXXQKLISXXXLSGSXXXPS SSXXLIXXGXXXXLX-XXLXFTGRXFXTX-LXXX [SEQ ID NO: 14] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVSSITSSGDGTYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAGGIAAAYAFDIWGIRGTLVTVSSGGGGSGGGGS (2) GGGGSQSVLTQPRSASGTPGQRVTISCSGSSSNVGSNYVYWYQQLPGTAPKWYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYORSYDSSRWVEGGXTKLTVLGEQXLISEEXLSGSAA [SEQ ID NO: 15] IL-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSGITWNSGSIGYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGPSVAARRIGRHWYNWFDPWGQGTIAMISSGGGG (1) TSGGGGSGGGGSQSVEQPPSASGTPGQRVTISCSGSSSNIGSNSVYWYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEXXADYYCQSYDSSLSGSVFGGXXKLXVLGEQKLISEXXL SGSAA [SEQ ID NO: 16] IL-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYNIHWVRQPPGKGLEWVSGVSWNGSRTHYADSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDPAMVRGVVLPNYYGLDVWGQGTLVIVSSGGGGS (2) GGGGSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGHSNRPSGVPDRFSGSKSGTSASLAISGLRSEXXADYYCQSYDSSISYPVEGGXTKLTVLGEQ [SEQ ID NO: 17] IL-8 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYGMSWVRQAPGKGLEWVSLISWDGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDDLYGMDVWGQGTLVTVSSGGGGSGGGGSGGGGS (1) QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYDNNKRPSXVPDRFSGSKSETSASLAISGLRSEDEADYKAAWDDSLSGWVEGGXTKLTVLXRIKLISEXXLSGSAA [SEQ ID NO: 18] IL-8 EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYEMNRANRQAPGKGLEWVSSISSSSSYIFYADSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNESVDPLGGQYFQHWGQGILVTVSSGGGGSGGG (2) TGSGGGGSQSVLTQPPSASGPGQRVTISCEGSSSNIGAGYDVFIWYQQLPETAPKWYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSAVVDDNLDGPVEGGXTKLTVLXEQKLISXXXLSGS AA [SEQ ID NO: 19] IL-9 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSSISSSSSYNYADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYMFGHWGQGTLVTVSSGGGGSGGGGSGGGGSQSVLTQPP (1) SASGTPGQRVTISCSGSGSNIGDNSVNWYQQLPGTAPIKLLIYGNNNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSSYISSSVVEGGXTKLTVLXEQKLISEXIDLSGSAA [SEQ ID NO: 20] IL-9 EVQLLESGGGLVIRPGGSLRLSCAASGHTSSYGMHWVRQAPGKGLEVIVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYKAKSPGGSPYYFDYWGQGTLVTVSSGGGGSGGGGSGG (2) GGSQSVLTQPPSASGTPGQRVTISCSGSVSNIGSNVVSWYQQLPGTAPKLLIYDNNKRPS [SEQ ID NO: 21] IL-9 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNISKNTLYLQMNSLRAEDTANNYCAKSPGGSPYYFDYWGQGTLVTNISSGGGGSGGGGS (3) GGGGSQSVLTIRPRSASGTPGQRVTISCSGSVSNIGSNIVVSWYQQLPGTAPKLLIYDNINKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLGGWVFGGXTKLTVLGEQKLISEXDLSGS AA [SEQ ID NO: 22] IL-10 EVQLLESGGGLVQPGGSLRLSCAASGFTFRSYVMSWVRQAPGKGLEWNISAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGKGRWAFDIWGQGTLVTVSSGGGGSGGGGSGGG (1) GSQSVLTQPPSASGTPGQRVTISCTGSSSNVGAGYDVHWYQQLPGTAPKWYRNNQRPSGVPDRESGSKSGTSASLAISGLRSXDXADYYCAAWDDSLSAHVVEGGXTKLTVLGEQKLISXXDLSGSAA [SEQ ID NO: 23] IL-10 EVQLLESGGGLVQPGGSLRLSCAASGFTFRSYVMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGKGRWAFDIWGQGTIATIVSSGGGGSGGGGSGGG (2) GSQSVLTQPPSASEIPGQRVTISCTGSSSNVGAGYDVHWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAVVDDSLSAHVVEGGXTKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 24] IL-10 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSAISGSGGSMADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCARGKGRWAFDIWGQGTLVTVSSGGGGSGGGGSGGGGSQ (3) SVLTQPPSASGTPGQRVTISCTGSSSNIGAGYGVHWYQQLPGTAPKLINGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLSGLVEGGXTKLTVIXEQKLISEXXLSGSAA [SEQ ID NO: 25] IL-11 EVQLLESGGGLVQPGGSLRLSCAASGFIFSNFGMFEWVRQAPGKGLEWVAFIRYDGSNKYVADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYKARHYYYSETSGHPGGFDPWGQGTLVTVSSGGGGSGG (1) GGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSYPVNWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSETSASLAISGLRSEDEADYYCQXGTGVEGGXTKLTVLGEQKLISXEXLSGSAA [SEQ ID NO: 26] IL-11 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTANNYCARHYYDVSYRGQIRDAFDIWGQGTLVIVSSGGGGSG (2) GGGSGGGGSQSNILTQPPSASGTPGQRVTISCIESSSNLGSPYDVHWYQQLPGTAPKWYRNDQRASGVPDRFSGSXSGISASLAISGLRSEDEADYYCAAWDDSLNAWVEGGKIKLTVLGEQKLISEXXLSG SAA [SEQ ID NO: 27] IL-11 EVQLLESGGGLVIRPGGSLRLSCAASGFITSDYYMSWIRQAPGKGLEWVAYISGISGYTNYADSVRGRFTISRDNSKNITLYLQMNSLRAEDTAVYKAKSKDWVNGGEMDVWGQGTLVTVSSGGGGSGGGGS (3) GGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYVVHWYQQLPGTAPKLLIVSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYKAAWDDSLRGWVFGGXTKLTVLGEQKLISEEDLSGSAA [SEQ ID NO: 28] IL-12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLENANSAIGTGGGTYYADSVIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAFRAFDIWGQGTLVTNISSGGGGSGGGGSGGGG (1) SSQSVLTQPPSASGTPGQRVTICSGSRSNIGNNFVSWYQQLPGTAPKWYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGPVFGGXTKLTNILGEQKLISEXDLSGSAA [SEQ ID NO: 29] IL-12 EVQLLESGGGLVQPGGSLRLSCAASGFTESDYYMSWNIRQAPGKGLEWNISGVSWNGSRTHYADSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSRSSPDAFDIWGQGTLVTVSSGGGGSGGGGS (2) GGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVFIVVYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYKAAVVDDRVNGRVEGGGTKLTVLGEQKLISEXXLSGS AA [SEQ ID NO: 30] IL-13 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSGSSYIYYADSVIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSQGWWTYYYGMDVWGQGTLVTVSSGGGGSGGGG (1) SGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKWYSNNQRPSGNIPDRFSGSKSGTSASLAISGLRSEDEADYYCETWGQ [SEQ ID NO: 31] IL-13 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYSMNWRQAPGKGLEVVVSSISSGSSYIYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAWYCARSQGWWTYYYGMDVWGQGTLVTVSSGGGGSGGGGSG (2) GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRESGSKSGTSASLAISGLRSEDXADYYCETXDSNIQIFGGXTIKLTVLGEQKLISEEXLSGSAXAHH HHHH-SXRXPIXXIVSXITIHXXSFXNVVTGKXXALPXXXALQHIPXXXAXXXX [SEQ ID NO: 32] IL-13 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPEKGLEWVSSISSGSSYMADSVIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSQGWWTYYYGIADVWGQGTLVTVSSGGGGSGGGGS (3) GGGGSQSVETQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKWYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCETWDSNTQIEGGXTKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 33] VEGF EVQLLESGGGLVQPGGSLRLSCAASGFIFSSNEMSWIRQAPGKGLEWVSSISGSGGFTYYADSVKGRYTISRDNSKNTLYLQMNSLRAEDTAVYYCAREITVRGNM'DIWGQGTLVTVSSGGGGSGGGESGG (1) GGSQSVLTQPPSASGTPGQRVTISCTGGSSNIGAGYDVHWYQQLPGTAPKILIYRNNQRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYYCAAWDDSLSVPMFGGXTKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 34] VEGF EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGIKGLEWVSGINWNGGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASSVGGWYEGDNIWFDPWGQGTLVTVSSGGGGSGG (2) GGSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYGNSNRPSXVPDRFSGSXSGTSASLAISGLRSEXEADYYCQSYDGSLSGSVEGGXTKLTVLGEXKLISEXXLSGSA A [SEQ ID NO: 35] TGF- EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMSVVVRQAPGKGLEVVVAVVSIDGGTTYYGDPVKGRFTISRDNISKNTLYLQMNSLRAEDTAVYYCTRGPTLTYYFDYVVGQGTLVTNISSGGGGSGGG β1(1) GSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKWYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGWVFGGXTKLXVLGEQKLISEEDLSGSAA [SEQ ID NO: 36] TGF- EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMSWFRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGNRPLDYWGQGTINTNISSGGGGSGGGGSGGGG β1 (2) SQSVETQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYGNISNRPSGVPDRESGSKSGTSASLAISGLRSEDEADYKAAWDDRLNGWVFGGGTKLXVLGEQKLISEXDLSGSAA [SEQ ID N0: 37] TGF- EVQLLESGGGLVQPGGSLRLSCAASGFIFSDYYIGWIRQAPGKGLEWVSGINWNGESTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRSTPSSSWALPDFFDYWGQGTLVTVSSGGGGSGG β1 (3) SGGSGGGESQSVLTQPPSAGTPGQIWTISCTGSSSNIGANYDVHWYQQLPGTAPKWYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCQSYDSSLSGWVEGGXTKLTVLGEQKLISXXXLSGSA A [SEQ ID NO: 38] TNF-α EVQLLESGGGLVQPGGSLRLSCAASGFTEDDYGMSWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRHLGSAMGYWGQGILVTVSSGGGGSGGGGSGGGGS (1) QSVLTQPPSASEIPGQRVTISCTGSSSNIGAGYDVFIVQQQLPGIAPKLLIYGNSNRPSXVPDRFSGSXSETSASLAISGLRSEDEADYYCQSYDSSLSGWVEGGXTKLTVLXEQKLISXXDLSGSAA [SEQ ID NO: 39] TNF-α EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYGMHWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCARGGWGPRSAFDIWGQGTLVIVSSGGGESGGGGSGG (2) GESQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVTWYQQLPGTAPKLLIYGNTNRLSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCEAWDDKLFGPVFGGXTXLTVLXEQKLISEXXLSGSAA [SEQ ID NO: 40] TNF-α RfQLLESGGGLVQPGGSLRLSCAASGFTESSYWMSWVRCLAPGKGLEWVSGVNWNGSRTHYADSVKGRFTISRDNSKNTLYLCIMNSLRAEDTAVYYCASIRANYYYGMDVWGQGTLVTVSSGGGGSGGGGS (3) GGGGSCLSVLTQFPSASGTPGQRVTISCSGGSSNIGSHPVNWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDASLSGWVFGGGXKLIVLXEXKLISXXXLSGSAA [SEQ ID NO: 41] GM- EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGGNASAPVDYWGQGTLVTVSSGGGGSGGGGSG CSE GGGSQSVLIQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYDNNKRPSGVPDRXSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLIGLVVFGGKTKLIVLGEQKLISEXXLSGSAA (1) [SEQ ID NO: 42] GM- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVAVISYDGSNEDSADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGPSLRGVSDYWGQGTLVTVSSGGGGSGGGGSGGG CSF GSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYNDNQRPSXVPDRFSGSKSGTSASLAISGLRSEDEADYYCQTWGTGINVIFGGXTKLXVLGEQKLISXEDLSGSAA (2) [SEQ ID NO: 43] GM- EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMSWVRQAPGKGLEWVAVISYDGSNEDSADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGPSLRGVSDYWGQGTLVTVSSGGGGSGGGGSGGG CSF GSQSVLIQPPSASGIPGQRVTISCTGSSSNIGAGYDVHWYCLQLPGTAPKWYNDNQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCCLTWGTGINVIEGGXTKLIVLGEXKLISEXXLSGSAA (3) [SEQ ID NO: 44] TNF-β EVQLLESGGGLVQPGGSLRLSCAASGFTESSFAMHWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASRSTLYYYYGMDVWGQGTLVTVSSGGGGSGGGGSG (1) GGGSQSVLTIRPPSASGTPGQRVTISCSGSTSNIGNSHVYWYQQLPGIAPKWYGNSNRPSXVPDRFSGSXSGTSASLAISGLRSEDEADYYCSSXAGSNNLVEGGXTKLIVLGEQKLISXXDLSGSAA [SEQ ID NO: 45] TNF-β EVQLLESGGGLVIRPGGSLRLSCAASGHTSSYAMSWVRCLAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLIRMNSLRAEDTAVYYCARSPYYGMDVWGCLGTLVTVSSGGGGSGGGGSGG (2) GGSCLSVLTCLPPSASGTPGCLRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYRNDQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADWCSSYGGRDNVVFGGXTKLTVLXEQKLISXXXLSGSAA [SEQ ID NO: 46] IL-1ra EVQLLESGGGLVQPGGSLRLSCAASGFTEDTHWMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHDYGDYRAFDIWGQGTLVTVSSGGGGSGGGGSGG (1) GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYVVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCCLSYDSSLSGVVFGGXTKLXVLXECLKLISXEDLSGSAA [SEQ ID NO: 47] IL-1ra EVQLLESGGGLVQPGGSLRLSCAASGFTFSKYAMTWVRQAPGKGLEWVSAISGSGGNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLVRGLYYGMDVWGQGTLVTVSSGGGGSGGGGSGG (2) GGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSXDEADYYCQTXGTGPVVFGGXTKLTVLGEQKLISXXXXSGSAA [SEQ ID NO: 48] IL-1ra EVQLLESGGGLVQPGGSLRLSCAVSGHTSSYSMNWVRQAPEKGLEWVAGIGGRGATTYYVDSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARLRVVPAARFDYWGQGTLVTVSSGGGGSGGGGSGGG (3) GGSQSVLTQPPSASGTPQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKWYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGPPWVEGGXXKLXVLXEQKLISEEDLSGSAA [SEQ ID NO: 49] IL-16 EVQLLESGGGLVQPGGSLRLSCAASGFTESNHAMSWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDIAVYYCARAALVQGVIKHAFEIWGQGILVIVSSGGGGSGGGG (1) SGGGGSQSVLIQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTALKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCASWDDRLSGLVFGGXTKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 50] IL-16 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNHAMSWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAALVQGVKHAFEIWGQGTLVTVSSGGGGSGGGGS (2) GGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTALKLLIYRNNQRPSGVPDRFSGSXSGISASLAISGLRSEXEADYYCASWDDRLSGLVEGGXTIKLTVLXEQKLISEEDLSGSAA [SEQ ID NO: 51] IL-18 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYGMHWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVWCARDLRGGREDPWGCLGTLVTVSSGGGGSGGGGSGGGG (1) SQSVLTCLPPSASGTPGQRVTISCTGSSSNIGAGYVVRWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYYCSSXAGSKNLIFGGXTKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 52] IL-18 EVQLLESGRGLVQPGGSLRLSCAASGFTESSYGMFEWVRQAPGKGLEWVSAIGIGGDMADSVMGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSPRRGATAGTFDYWGIRGTLVTVSSGGGGSGGGGSG (2) GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNIVNWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADWCXSYDNSLSGWVEGGXXKLXVLGEXKLISEXDLSGSAA [SEQ ID NO: 53] MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYGMFIWVRCLAPGKGLEWVSGISWNGGKTHYVDSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYSSGWAFDYWGQGTIAMISSGGGGSGGGGS 4 (1) GGGGSQSVLTQPPSASGTPGQRVTISCSGRSSNIESNTVNWYCLQLPGTAPKWYGNSNRPSGVPDRESGSKSGTSASLAISGLRSEDEADYYCAAWDDRLNAVVEGGXTKLTVLGECLKLISEXDLSGSAA [SEQ ID NO: 54] IFN-γ EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGRTGFIGWKYYFDLWGQGTLVTVSSGGGGSGGGG (1) SGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPGTAPKWYGNSNRPSXVPDRFSGSXSGTSASLAISGLRSEDEADYYCQXWGTGLGVEGGXTKLTVIGEXKIISFFXISGSAA [SEQ ID NO: 55] IFN-γ EVQLLESGGGLVQPGGSLRLSCAASGFIFSRFIGFHWVRQGPGKGLEWVSGVSWNGSRIFIYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGNWYRAFDIWGQGTLVIVSSGGGGSGGGGSGG (2) GGSQSVLIQPPSASGTPGQRVTISCSGGSSHIGRNFISWYQQLPGTAPKLLIYAGNSRP [SEQ ID NO: 56] IL-1β EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRSTISRDNSKNTLYLQMNSLRAEDTAVYYCARVRQNSGSYAYWGQGILVTVSSGGGGSGGGGSGGG (1) GSQSVLTQPPSASEIPGQRVTISCTGISSNIGAPYDVHWYQQLPGTAPKWYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCQSYDSSLSAVVEGGXIKLTVLGEQKLISEXXLSGSAA [SEQ ID NO: 57] IL-1β EVQLLESGGGLVQPGGSLRLSCAASGFIFSRWMTVVVRQAPGKGLEWVSLISGGGSATYYADSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRVPYDSSGYYPDAFDIWGQGTLVTVSSGGGGSGG (2) GGSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDQFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLINGPVEGGXTXLTMEQKLISEEXLSGS AA [SEQ ID NO: 58] IL-1β EVQLLESGGGLVQPGGSLRLSCAASGETESSYWMSWVRQAPGKGLEWVAVVSYDGNNKYYADSRIKGRETISRDNSKNTLYLQMNSLRAEDTAMYYCASYWYTSGWYPYGMDVWGQGTLGTVSSGGGGSGGG (3) GSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDLHWYQQLPGTAPKWYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSSYVDNNNLVEGGXTKLTVLXEQKLISEXXLSGSAA [SEQ ID NO: 59] Eotaxin EVQLLESGGGLVQPGGSLRLSCAASCiFTESSYWMSWVRQAPGKGLEMSGVSWNGSRTHYADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCVKGKGTIAMPGRARVQNVVGQGTLVIVSSGGGGSGG (1) GGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPGTAPIKLLIYANSNRPSGVPDRESGSXSGTSASLAISGLRSEDEADYYCAAWDDSLSGPVEGGXTKLTVLGEQKLISXXDLSX SAA [SEQ ID NO: 60] Eotaxin EVQLLESGGGLVQPGGSLRLSCAASGETESAYWMTWVRQAPGKGLEMSVIYSGGSTYYADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCARQTQQEYEDYWGQGILVTVSSGGGGSGGGGSGGGGSQ (2) SVLTQPPSASGTPGQRVTISCFGSNSNIGSSTVNWYQQLPGTAPKLLIYDNDKRPSGVPDRESGSXSGTSASLAISGLRSEDEADYKAAWDDSLNGPVEGGXTKLTVLGEQKLISXXXLSGSXAAHHHHHH- SPRXPIRPIVSXXTIHWPSFYNVXTGKXXXLPNXIXXXHIPLSPAXXIXXXPXXXXX [SEQ ID NO: 61] Eotaxin EVQLLESGGGLVQPGGSLRLSCAASGFTFRGYAMSWVRQAPGKGLEMSGVSVVNGSRTHYADSVIKGRETISRDNSKNTLYLQMNSLRAEDTAWYCARAPAVAGWEDPWGQGTLVTVSSGGGGSGGGGSGGG (3) GSQSVLIQPPSASGTPGQRVTISCSGSSSNIGSKIVNWYQQLPGTAPIKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLSGRVXGGGXKLTVLGEQKLISEEDLSGSAA [SEQ ID NO: 62] RANTES EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISNDGTIKKDYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAMCARDASEYDDYYMYWGQGTLVTVSSGGGGSGGGGSGGG (1) GSQSVLTQPPSASGTPGQRVTISCIGSSSNIGAGSDVFEWYQQLPGIAPKWYRDDQRSSGVPDRESGSKSGTSAFLAISGLRSEDEADYYCQSYDNSLSGWVEGGXTKLIVLGEQKLISEXXLSGSAA [SEQ ID NO: 63] RANTES EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDNDYSSDTFDYWGQGTLVTVSSGGGGSGGGGSGG (2) GGSQSVLTQPPSAFGTPGQRVTISCSGSSSNIGSDYVYWYQQLPGTAPKWYSDNIRRP [SEQ ID NO: 64] RANTES EVQLLESGGGLVQPGGSLRLSCAASGETESNYGMNINVRQAPGKGLEWNISGVSWNGSRTHYNIDSVIKRRETISRDNSIKNTLYLQMNSLRAEDTANNYCARPRLRSHNYYGMDVWGQGTLVTNISSGGGG (3) SGGGGSGGGGSQSVI3CIPPSASGTPGQRVTISCSGSSFIKSGKNYVSWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDNIRVKGVIEGGXTKLTVLGEQKLISE XDLSGSAA [SEQ ID NO: 65] MCP- EVQLLESGGGINCLPGGSLRLSCAASGETESSYAMSWVRQAPGIKGLEMSGVSWNGSRTHYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGGFIQQLGQNGQGTLVINISSGGGGSGGGGSGG 1 (1) GGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNWSWYQQLPGTAPKWYRDSRRPSGVPDRFSGSKSGTSASLAISGLRSEXEADYYCAAWDDSLKGWLEGGXTKETVLXEQKLISEXXLSGSAA [SEQ ID NO: 66] MCP- EVQLLESGGGLVQPGGSLRLSCAASGETESSYAMSWVRQAPGKGLEWVSYISSSSSYTNYADSVKGREMRDNSKNTLYLQMNSLRAEDTAVYYCARERYNSGKIVIEDYINGQGTINTVSSGGGGSGGGGSG 1 (2) GGGSQSVLTQPPSASETPGQRVTISCSGSSSNIGRNTVNINYQQLPGTAPKLLIYGNSNRRSGVPDRESGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGWEGGXTKLTVLXEQKL1SEXDLSGSAA [SEQ ID NO: 67] MCP- EVQLLESGGGLVQPGGSLRLSCAASGETESNYGMHWVRQAPGKGLEWVAVISYDGSNMADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCAKSHYYDTTSEDYWGQGTLVTVSSGGGGSGGGGSGGGG 1 (3) SQSVLTQPPSASGTPGQRVTISCSGSSSNIGTNPVNWYQQLPGTAPKLLIYDNNKRPSGVPDRESGSKSGTSASLAISGLRSEDXADYYCAAWDDSLSGVVEGGXTKLTVLGEQKLISXEDLSGSAA [SEQ ID NO: 68] MCP- EVQLLESGGGLVQPGGSLRLSCAASCiFTESTYGMHWVRQAPGKGLEWVSGVSVVNGSRTHYVNSVIKRRETISRDNSIKNTLYLQMNSLRAEDTAVYYCARVAPGSGKRLRAFDIWGQGTINTVSSGGGGS 3 (1) GGGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPGTAPKWYEVSKRPPGVPDRESGSKSGTSASLAISGLRSEDXADYYCSSYAGSSKWVEGGKIKLIVLGEQKLISEEDLSGSA A [SEQ ID NO: 69] MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTLSSNYMSWVRQAPGKGLEWVSGISASGHSTHYADSGKARFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGKSLAYWGQGTLVTVSSGGGGSGGGGSGGGGSQS 3 (2) VLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPGIAPKWYRNNQRPSGVPDRESGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSVVVEGGXTIKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 70] MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTESIYVVMSWVRQAPGKGLEWVAYIGGISNTVSYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAPGYSSGWGWEDPWGQGTLVTVSSGGGGSGGGG 3 (3) SGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGTNSVENNYQQLPGTAPKWYGNNNRPSGVPDRESGSKSGTSASLAISGLRSEDXADYYCMIWHSSASVFGXXTKLTVLGEQKLISEXXLSGSAA [SEQ ID NO: 71] β- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMHWVRQAPGKGLEWVAVIAYDGINEYYGDSVKGRETISRDNSKNTLY1QMNSLRAEDTAVYYCARGGIYHGFDIWGQGTLVTVSSGGGGSGGGGSGGGG galacto- SQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYDNHKRPSGVPDRFSGSXSGTSASLA1SGLRSEDEADYYCAAWDDNSWVEGGXIKLIVLGKYKDDDDKAA sidase [SEQ ID N0: 72] Angio- EVQLLESGGGLVIRPGGSLRLSCAASGETESDHYMDWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRETISRDNISKNTLYLQMNSLRAEDTANNYCARDTWAYGAFDIWGQGTLVTVSSGGGGSGGGGSG motin GGGSQSVLTQPPSASGTPGQRVT1SCSGSNSNIGRNTVNVVYQQLPGTAPKLLEYRDNIRRPSGVPDRESGSXSGTPASLAISGLRSEDXADYKAAWDVSLNGWVEGGXTKLTVLGDYXDHDGDYKDHDIDX (1) XDDDDXXAAHHHHHH-SPRWXIRPIVSRITIXWXXFYXVXXXKXX [SEQ ID NO: 73] Angio- EVQLLESGGGLVQPGGSLRLSCAASGFTENDYYMTWIRQAPGKGLEWVSYISSSGSTMADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARERLPDVEDVWGQGTLVTVSSGGGGSGGGGSGGGGSQ motin SNILTQPPSASGTPGQRNITISCSGSGSNIGTNSVSWYQQLPGTAPKIIIYEDDLLPSGVPDRESGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGVVFGGXTKLTVLGXYKDHDGDYKDHDIDYKDDD (2) XKAXAHHHHHH-SPRXXXRXIVSXIXIHXXXFYNXXTGKTXXXXXXIXXAAXXXFXX [SQS ID N0: 74] Leptin EVQLLESGGGLVIRPGGSLRLSCAASGFTEGDFAMSWVRQAPGKGLEWVANIKQDGSVKYYVDSVKGRFTISRDNSKNTLYLIRMNSLRAEDTAWYCARELAGFYYGMDVWGQGTLVTVSSGGGGSGGGGSG GGGSQSVLTQPPSASGTPGQRVTISCSGSDSNIGGNTVNVVYQQLPGMAPKIIIYYDDLLPSGVPDRESGSKSGTSASLAISGLRSEDEADYYCAAYDDTMNGWGEGGXTKLTVLGXYKDXDDKAA [SEQ ID NO: 75] Integrin EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYNMNWVRQAPGKGLEWVSTISGSGGRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVATLDAFDIWGQGTLNITVSSGGGGSGGGGSG α- GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNSVSWYQQLPGTAPKWYSNNIRRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGVVFGGXTKLTVLGEQKLISEXDLSGSAA 10 [SEQ ID NO: 76] Integrin EVQLLESGGGLVQPGGSLRLSCAASGFTFRRDWMSWVRCWPGKGLEWVSVISGSDGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASYSPLGNWFDSVVGDGTLVTVSSGGGGSGGGGSGG α-11 GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYSDTYRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYYCQSYDSSLXGFVVFGGXTKLTVLXEQKLISEXXISGSAA [SEQ ID NO: 77] IgM EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWERQAPGKGLEWVSAIGSGPYYAHSVRDRFTISRDNSKNTLYLDVINSLRAEDTAVYYCARGGVEASFDYWGQGTLVTVSSGGGGSGGGGSGGGGSQ (1) SVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVERNYQQ1PGTAPKWYGNTNRPSGVPNRFSGSKSGTSASLAISGLRSEDEADYYCQSYDNDLSGMFGGXTKLXVILEQKLISXXXLSGSAA [SEQ ID NO: 78] LDL EVQLLESGGGLVQPGGSLRLSCAASGETESDYYMSWVRQAPGKGLEVVVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAARYSYYYYGMDVWGQGTLVTVSSGGGGSGGGG (1) SGGGGSQSVETQPPSASGTPGQRVTISCSGSSSNIGNNANINWYQQIPGTAPKLEAYGNDRRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQPNGTGRGVFGGGTKLTVLGEQKLISEXXLSGSAA [SEQ ID NO: 79] LDL EVQLLESGGGLVQPGGSLRLSCAASGETESNAWMSVVVRQAPGKGLEWVSSISTSSNYIYVADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARVKKYSSGWYSNYAFDIWGQGTLVTVSSGGGGSG (2) GGGSGGGGSQSVLIQPPSASGTPGQRVTISCSGSSSSIGNNFVSWYQQLPGTAPKLLEYDNNKRPSXVPDRFSGSXSGTSASLAISGLRSEDXADYYCAAWDDSLNGWVFGGXTKLTVLXXYKDHDGDYXDH DIDYKDXXDKAA [SEQ ID NO: 80] PSA EVCILLESGGGLVQPGGSLRLSCAASGETERSYEMNWVRQAPGKGLEWVAVIGGNGVDTDVADSVKGRETESRDNSKNTLYLQMNSLRAEDTANNYCVREEVDEWSGYYSYGIVIDVWGQGTLVIVSSGGGG SGGGGSGGGGSQSVLIQPPSASGTPGQRVTISCSGSSSNIGDNFVSWYQQ1PGIAPKWYRTNGRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYYCATWDDNLNGRVVFGGXTKLTVILDYKDXXDKAA [SEQ ID NO: 81] Lewis.sup.x EVQLLESGGGLVIRPGGSLRLSCAASGETESNYWMFIWVRQAPGKGLEWVANIKEDGSEKYWDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGETSFGLDVWGQGTLVTVSSGGGGSGGGGSGG (1) GGSQSVLTQPPSASGTPGQRVIISCSGSSSNIGSNTVNWYQQLPGTAPKWYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCASINDDSLSGWVFGGXTKLTVLGDYKDDDDKAA [SEQ ID NO: 82] Lewis.sup.x ENIDLLESGGGLVQPGGSLRLSCAASGFTFSRYWMHWVRQAPGKGLEWVANIKPDGSEQYYADSVKGRFTESRDNSKNTLYLDMNSLRAEDTAVYYCAREGLSSGWSYGMDVWGQGTLVTVSSGGGGSGGGG (2) SGGGGSQSVLTQPPSASGTPGQRVTISCSGSNSNIGSNTVNWYQQLPGTAPKLLIYTNIINRPSGVPDRFSGSKSGTSASLAISGLRSXDEADYYCATWDDSLSGWVFGGXTKLTVLGXYKDXXDKAA [SEQ ID NO: 83] Lewis.sup.y EVQLLESGGGLVQSGGSLRLSCAASGFTFSSYTLHWVRQAPGKGLEYVSAISSNGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASDVYGDYPRGLDYWGQGTLVTVSSGGGGSGGGGSG GGGSQSVLTQPPSASGTPGQRVTISCSGTISNIGSNYVFEWYQQLPGTAPKWYGNNNRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCQSYDRSLGGLRVEGGXTKLTVLXDYKXDDDKAA [SEQ ID NO: 84] Siallex EVQLLESGGGLVQPGGSLRLSCAASGFILSSYAMSWVRQAPGKGLEVVVSSISSGNSYNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGRGRGGGFELWGQGTLVTVSSGGGGSGGGGSGGG GSQSVLIQPPSASGTPGQRVTISCSGSSSNIGTYTN/NWYDQLPGTAPKLLIVSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEXEADYYCSSNAG1DNILFGGXTKLTVLGEQKL1SEXDLSGSXAAHHH HXXXXXXXXIXXXXXXXXXXXXXXXXXXLXX [SEQ ID NO: 85] TM EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGFHWVRQAPGKGLEWVSLESWDGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGTWFDPWGQGTLVTVSSGGGGSGGGGSGGGGSQS peptide VLTQPPSASGTPGQRVTISCSGSSSXIGNNAVNWYQQLPGTAPKLLIYRNNQRPSXVPDRFSGXXSGTSASLAIXGLRSEDEADYYCAAWDDSLSWVFGGXTKLTVLGDXXTMXVIIKIMTSXXXMTMXRRP [SEQ ID NO: 86] Pro- ENICILLESGGGEVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSSMSASGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRGSYGMDVWGQGTENTVSSGGGGSGGGGSGG cathep- GGSQSVLTQPPSASGTPGQRNITISCSGSTSNIGSYAVNWYQQLPGTAPKELIYGNNNRPSGVPDRFSGSXSGTSASLAISGPRSEDEADYYCAAWDDSLNGGVFGGXTIKLTVEGXYKXDDDKAA sin W [SEQ ID NO: 87] BTK EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHLKRYSGSSYLFDYWGQGTLVTVSSGGGGSGGGG (1) SGGGGSQSVLTQPPSASGTPGQRNITISCSGSSSXIGSNYVYWYQQLPGTAPKWY [SEQ ID NO: 88] Digoxin EVQLLESGGGLVQPGGSLRLSCAASGETESSYAMSWVRQAPGKGLEWVAVIWFIDGSSKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGDGFDYWGQGTLVTVSSGGGGSGGGGSGGGG SQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQ1PGTAPKWYRNNQRPSGVPDRFSGSKSGTSASLAISGERSEDEADYYCAAWDDSLNGVVFGGXIKLTVLGEQKLISXXXLSXSAA [SEQ ID NO: 89] GLP-1R EVCILLESGGGLVQPGGSLRLSCAASGETFRSYGMWANRQAPGKGLEVVVSGLSWNSAGTGYADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCAKENIGNNWDHIDYINGQGILVTVSSGGGGSGGG GSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLEYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDGLSGPVFGGGTKLTXLGEQKLISEEDLSGS AA [SEQ ID NO: 90] GLP-1 EVQLLESGGGLVIRPGGSLRLSCAASGETENSYGIVIHWVRQAPGKGLEVVVSAISGSGGSTMESVKGRSTISRDNISKNTLYLQMNSLRAEDTAVYYCVTRNAVEGFDWIGQGTLVTVSSGGGGSGGGGSG GGGSQSVLTQPPSASGTPGQRVTISCIGSSSNEGAGFDVFEWYQQLPGIAPKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSMSSLSGVVFGGXTKLTVLXEQKLISXEXLSGSAA [SEQ ID NO: 91] C1q EVCILLESGGGLVQPGGSLRLSCAASGFTFDDYGIVISWVRQVPGKGLEMISAISGSGATTFYAHSVQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGRGYDWPSGAFDPNGQGTLVTVSSGGGGSG GGGSGGGGSQSVLTQPPSASGIPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLEYENNKRPSXVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSVNGYVVFGEKTKLTVLGEQKLISEXX LSGSAAXXHHHHH-SPRWPIRPIXSRXTIMPSFYXXXXXXIXXLPXXIXXXHXPXXXXXX [SEQ ID NO: 92] C1s EVQLLESGGGLVIRPGGSLRLSCAASGETESSYAIVISWVRQAPGKGLEWVSGVSVINGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHMKAAAYVFEIWGQGTLVTVSSGGGGSGGG GSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSTAVNWYQQLPGTAPKWYSNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYKAAWDDRLNGNVLEGGXXKLTVLXEQXLISXXXLSGSAA [SEQ ID NO: 93] C3 (1) ENICILLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSSVTGSGGGTYYADSVEGRFTISRDNSKNTLYEQMNSLRAEDTAVYYCARYRWFGNDAFDIWGQGTLVTVSSGGGGSGGGGS GGGGSQSVLTQPPSASGTPGQRVTISCSGSASNLGMFINSWYQQLPGTAPKWYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYKAAWDDTLNIWVFGGXTKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 94] C3 (2) EVQLLESGGGLVQPGGSLRLSCAASGFIFSTYRMIWVRQAPGKGLEWVSSISGSNTYIHYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAWYCARDRHPLLPSGMDVWGQGTLVTVSSGGGGSGGGESGG GGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGKHPVNWYQQLPGTAPKLLIYRNDQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCQSYDSSLSGSWVEGGXTKLTVLGXQKLISEEDLSGSAA [SEQ ID NO: 95] C4 (1) EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYPMSWVRQAPGKGLEWVSTLYAGGWISYADSVWGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARPMIESLSRYGMDVWEQGTLVTVSSGGGGSGGGGSG GGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYVVHWYQQLPGTAPKLLIYDNSKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGVVFGGXTKLTVLXEQKLISEXXLSGSAA [SEQ ID NO: 96] C5 (1) EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYRMNWVRQAPGKGLEWVSAISGSGGSTYYADSVIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGGWFSGHYYFDYWGQGILVIVSSGGGGSGGGG SGGGGSQSVLTQPPSASGTPGQRVTISCTGATSNIGAGYDVHWYQQIPGIAPKWYRNNQRPSXVPDRFSGSXSEISASLAIXGLRSEDXADYYCQSYDSSLRHWVFXGXXKISIVLXEQKLISEXXLSGSXA [SEQ ID NO: 97] C5 (2) EVQLLESGGGLVQPGGSLRLSCAASGFTESAYSMNWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCARENSGFFDYWG0GTLVIVSSGGGGSGGGGSGGGGS QSVLTQPPSASGTPGQRVTISCTGSSSNIGSNTVNWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLTISGLRSEDXADYYCAAWDDSLSGWVFGGXTKLTVLXEQKLISEEXLSGSAA [SEQ ID NO: 98] C1 inh. EVQLLESGGGLVQPGGSLXLSCAASGFTFSDYYMSWIRQAPGKGLEWVSGISRGGEYTFYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDPGGLDAFDIWGQGILVTVSSGGGGSGGGGSGGG (1) GSQSVLIQPPSASGTPGQRVTISCTGSSSNIGARYDVQWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEXXADYYCASWDDSLSGPVEGGXTKLIVLXEQKLISEXXLSXSAA [SEQ ID NO: 99] Factor EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVAVISYDGRFIYYSDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYGGNLAMDVWGIRGTLVTVSSGGGGSGGGGSGG B (1) GGSQSVLTQPPSASETPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYDNNKRPSGVPDRFSGSNSGTSASLAISGLRSEDXADYYCAAWDDRLNGRVVFGEXTKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 100] IL-12 EVQLLESGGGLVQPGGSLRLSCAASGFTBRYGMHWVRQAPGKGLEWVASIRGNARGSFYADSVKGRETISRDNSKNTLYLCIMNSLRAEDTAVYYCAKGDSSGWYFFDYWGIRGTLVTVSSGGGGSGGGGSG (3) GGGSQSVLTQPRSASGTPGQRVTISCTGSDSXIGAGEDVHWYQQLPETAPKLLIYGNNNRPSGVPDRESGSKSGTSASLAISGLRSEDXADYYCQSYDTSLSGVLEGGXXKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 101] IL-12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYGMFIWVRQAPGKGLEWVSTVSGSGDNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYMTWRYWGQGTLVTVSSGGGGSGGGGSGGGGSQSVLT (4) QPPSASGTPGQRVTISCSGSSSNIGSNTVNIWYQQIPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGWVEGGXTKLTVIXEQKLISXEDLSGSAA [SEQ ID NO: 102] IL-16 EVXLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARERGDAFDIWGQGTLVTVSSGGGGSGGGGSGGGGS (3) QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKWYSDNQRPSGVPDRFSGSKSGTSASLAISGLRSXXEADYYCAAWXDSLNGPWVEGGXTKLXVlGEQKLISEEDLSGSAA [SEQ ID NO: 103] IL-18 EVQLLESGGGLVQPGGSLRLSCAASGFIFSRYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHGYGDSRSAFDIWGQGTLVIVSSGGGGSGGGGSG (3) GGGSQSVLTQPPSASGTPGQRVTISCSIGSSSNIGAGYDVFIWYQQLPGTAPKWYRNNQRPSGVPDRFSGSXSGTSASLAISGLRSEXXADYYCQSYDSSLSRWVEGGXTKLXVLGEQKLISXXXLSXSAA [SEQ ID NO: 104] IL-1a EVQLLESGGGLVQPGGSLRLSCAASGFTESSYSMNWVRQAPGKGLEWVSYISSSSSYTNYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARSVTRRAGYYYYYSGMDVWGQGTLVTVSSGGGGSG (3) GGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSXIGSNIVNWYQQLPGTAPKWYRNNQRPSXVPDRFSGSXSGTSASLAISGLRSEDEAXYYCSSXAGSNSXVEGGXTKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 105] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYGMHWVRQAPGKGLEWVSSITSSGDGTYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAGGIAAAYAFDIWGQGTLVTVSSGGGGSGGGGSG (3) GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNVGSNYVYWYQQLPGIAPKWYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEXEADYYCQSYDSSRWVFGGXIKLIVLGEQKLISEXXLSGSAA [SEQ ID NO: 106] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSNYMSWVRQAPGKGLEWVSSISSSSTIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARQPASGTYDAFDIWGQGTLVTVSSGGGGSGGGGSGG (4) GGSQSVLTQPPSXSGTPGQRVTISCIGSSSNIGAGYDVHWYQQLPGTAPKLLIYYDDLLPSGVPDRFSGSKSETSASLAISXLRSEDEADYYCAVWDDSLSGWVEGGXTKLTVLXEQKLISMDLSGSAXAHH HHHHHXSPRXXIRPIVSXITIHXXVVLXRRDWEXPXXTQLNXXXAHXPEXXXXNX [SEQ ID NO: 107] IL-8 EVQXLESGGGLVQPGGSLRLSCAASGFTEDDYGMSWVRQAPGKGLEWVSLISWDGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDDLYGMDVWGQGTLVTVSSGGGGSGGGGSGGGGS (3) QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSETSASLAISGLRSXDEADYYCAAWDDSLSGWVEGGXTKLTVLGEQKLISEXXLSGSAA [SEQ ID NO: 108] MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVSGISWNGGKTHYVDSVKGQFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYSSGWAFDYWGQGTLVTVSSGGGGSGGGGSGG 4 (3) GGSQSVLTQPPSASGTPGQRVTISCSGRSSNIESNTVNWYQQLPGTAPKWYGNSNRPSGVPDRESGSKSGTSASLAISGLRSEXEADYYCAAWDDRLNAVVEGGXTKLXVLXECIKLISEXXLSGSAA [SEQ ID NO: 109] Properdin EVQLLESGGGLVQPGGSLRLSCAASGFTFSSNYMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGGSGWYDYFDYWGQGTLVTVSSGGGGSGGGGSGG GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEAXYYCAAXDDGLNSPVEGGGTKLXVLXEQKLISEEDLSGSAXAHHH HHH-SPRXXIRPIVSRITIHWXXFXXXXXGKTXXXPXLXXXXXXPPFX [SEQ ID NO: 110] TNF-β EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSGLSGSAGRTHYADSVRGRFTISRDNSKNTLYIKIMNSLRAEDTAMYYCASSLFDYWGQGTLVTVSSGGGGSGGGGSGGGGSQS (3) VLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLNAVVFGGXTKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 111] TNF-β EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMNWVRQAPGKGLEWVSGINWNSDDIDYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAMYYCAIDSRYSSGWSFEYWGQGTINTVSSGGGGSGGGGSG (4) GGGSQSVETQPPSASGTPGQRVTISCSGSTSNIGNSHVYWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSLSGVVFGGXTKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 112] VEGF EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYEMNINVRQAPGKGLEWVSGISGSGGETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAMYYCAREGYQDAFDIWGQGTPTIVSSGGGGSGGGGSGGG (3) GSQSVITQPPSASEIPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYSNNQRPSXVPDRFSGSXSEISASLAISGLRSEDXADYYCAAWDDSLSGPPWVFGGGXKLXVLXEQKLISXXXLSGSXAA HHHHHH-SPRXPIRPIVSXIX!FIWPXFYNVXXXXTXXXPXLX [SEQ ID NO: 113] VEGF EVQLLESGGGLVQPGGSLRLSCAASGFIFXXXYXSWVRQAPGKGLEVVVSXISWXXGSIGYADSVKGRFTISRDNSliNTLYLQMNSLRAEDTAVYYCXXXXXXXXNYEDYWEQGTLVTVSSGGGGSGGGGS (4) GGGGSQSVLTQPPSASGTPGQRVTISCSGSNSNIGGNEVYWYQQLPGTAPKLLIYENSKRPSXVPDRFSGSXSGTSASLAISGERSEDXADYYCAAWDDSLXXVVEGGXTIKLTVLGEQKLISXXXLSGSAA [SEQ ID NO: 114] IL-4 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAIAARPFDYWGQGTLVTVSSGGGGSGGGGSGGG (3) GSQSVLTQPPSASGTPGQRVTISCTGATSNIGAGYDIHWYQQLPGTAPKLLIYSTNNRPSGVPDRESGSKSGTSASLAISGLRSEDXADYKAAWDDSLNGPVEGGXXIKESIVLGEQKLISEXDLSGSAA [SEQ ID NO: 115] MUC- EVXLLESGGGLVQPGGSLRLSCAASGFTFSNYWMSWVRQAPGKGLEWVALISFDGSNKYYADSAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVLAQQRMDVWGQGTLVIVSSGGGGSGGGGSGGG 1 (1) QGSQSVLIQPPSASGTPGRVTISCSGSSSNIGSNITVNWYQQLPGTAPIKLLIYGNNNRPSGVPDRFSGSXSGTSASLAISGLRSED [SEQ ID NO: 116] CD40 EVQLLESGGGLVQPGGSLRLSCAASGFTESAYVVMHWVRQAPGKGLEVVVSGISGGGGSTYYADSVKGRETISRDNSIKNILYLQMNSLRAEDTAVYYCARMTPWYYGMDVWGQGTLVTVSSGGGGSGGGG (2) SGGGGSQSMLTQPPSASGTPGQRVTISCSGSTS [SEQ ID NO: 117] CD40 EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWLSYISGGSSYIFYADSVRGRFTISRDNSENALYLQMNSLRAEDTAVWCARILRGGSGMDLWGQGTLVTVSSGGGGSGGGGSGGGG (3) SQSVLTQFPXXSGTPGQRVTISC [SEQ ID NO: 118] CD40 EVQLLESGGGLVQPGGSLRLSCAASGFTESTYGMFEWVRQAPGKGLEWLSYISGGSSYIFYADSVRGRETISRDNSENALYLQMNSLRAEDTAVYYCARILRGGSGMDLWGQGTLVTVSSGGGGSGGGGSGG (4) GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVYVVYQRLPGTAPKLLIYGNINRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLXGLVEGGXXKLTVLXXYKDDDDKAA [SEQ ID NO: 119] CT17 EVQLLESGGGLVQPGGSLRLSCAASGFTESSSAMHWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVKGRVTIFGVVINSNYGMDVWGQGTINTVSSGGG GSGGGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSISSIGSNAVSWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLNGHDVVEGGXTKLTVLXDYKDXDX KAA [SEQ ID NO: 120] IgM EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMSWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAWYCARGDYSSSPGGYVYYMDVINGQGTLVTVSSGGGGSGG (3) GGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSXIGSNTVNVVYQQLPGTAPKLLIYGNSNRPSXVPDRFSGXXSGTSASLAIXGLRSXDXADYYCSSXXSTNTVIEGGXTKETVLGEQKLISXXDLSGS AA [SEQ ID NO: 121] IgM PAILLESGGGLVQPGGSLRLSCAASGFTESSNEMSWIRQAPGKGLEWVSAIYSGGGTYYADSVIKGRFTISRDNSKNTLYLQJVINSLRAEDTAVYYCARVNDYGDNVYFDHWGQGTLVIVSSGGGESGGGG (4) SGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYENNKRPSXVPDRFSGSXSGTSASLAISGLRSEDEADYYCAAWDDSLSVYVVFGGXTKLXVLGEQKLISXXDLSGSA A [SEQ ID NO: 122] IgM EVQLLESGGGLVQPGGSLRLSCAASGETEGSVEMNWVRQAPGKGLEMSVIYSGGSTYYADSVEGRFTISRDNSKNTLYLQMNSLRAEDIAVYYCARDTNPYYYYGMDVWGQGTLVTVSSGGGGSGGGGSGGG (5) GSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPGTAPKLLIYRNNQRPSXVPDRFSGSKSGTSASLAISGLRSEDEADYYCQSYDSSINGQVEGGXTKLTVLXRIKLISXEXLSGSAA [SEQ ID NO: 123] HLA- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSAISGSGGSMADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCARDGLLPLDYWGQGTLVIVSSGGGESGGGGSGGGESQS DR/ VLTQPPSASGTPGQRVTISCSGGSSNIGGNAVNWYQQLPGTAPKLLIYENNIKRPSXVPDRFSGSXSGTSASLAISGLRSEDXADYYCSSYAVSNNFEVLEGGXTKLTVLXEQKLISXXDLSGSAA DP [SEQ ID NO: 124] ICAM- EVQLLESGGGLVQPGGSLRLSCAASGFIFSNAWMSVVVRQAPGKGLEWVAFIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSGWYFDYWGQGTLVIVSSGGGGSGGGGSGGGG 1 SQSVLIQPPSASGTPGQRVTISCTGSSSXIGAGYDVHVVYQQLPGTAPKLLIYDNNNRPSXVPDRFSGSXSGTSASLAISGLRSEDEADYYCQSYDSSLSAWLFGEXTKLTVLGEQKLISXXDLSGSXAAHH HHHH-SPRWPIRXIVSXXTIXXPXFYXVXXXKPXXTXLXRXXAHPXX [SEQ ID NO: 125] IgM PAILLESGGGINQPGGSLRLSCAASGFIFSDYYMSWIRQAPGKGLEMSAIGSGMAHSVRDRFTISRDNSIKNTLYLQMNSLRAEDTAVYYCARGGVEASFDYWGQGTLVIVSSGGGESGGGGSGGGESQSVL (2) TQPPSASGTPGQRVIISCTGSSSNIGAGYDVHWYQQLPGTAPIKLLIYGNTNRPSXVPNRFSGSXSGTSASLAISGLRSEDEADYYCQSYDNDLSGWVEGGXTIKLTVLGEQKLISEEXLSGSAA [SEQ ID NO: 126] MUC- EVQLLESGGGLVIRPGGSLRLSCAASGFTFKNYWMSWVRQAPGKGLEWVSDISGGGGTTYIADSVKGRETISRDNSKNITLYLQMNSLRAEDTAVYYCARIFISGSYYFDYWGIRGTLVTVSSGGGGSGGGG 1 (2) SGGGGSCLSVLTIRPRSASGTPGQRVTISCTGSSSNIGAGYDVHWYCLQLPGTAPKLLIYIKNNCIRPSGVPDRFSGSKSGTSASLAIXGLRSEDEADYYCA [SEQ ID NO: 127] MUC- EVQLLESGGGLVQPGGSLRLSCAASGFTEKNYWMSWVRQTPGKGLEWVSDISGGGGTTYIADSVKGRETISRDNSIKNTLYLQMNSLRAEDTAVYYCARIHSGSYYMYWGQGTLVTVSSGGGGSGGGGSGGG 1 (3) GSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVFIWYQQLPGTAPKLLIYKNNQRPSGVPDRESGSKSGTSASLAISGLRSEDXADYYCAAWDDSLNGPVEGGXXKLTVLXDYXDHDGDYKDFEDIDY XDDDXXAA [SEQ ID NO: 128] MUC- EVQLLESGGGINQPGGSLRLSCAASGFTFKNYVVMSWVRQAPGKGEEWNISDISGGGGTTYIADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIHSGSYYFDYWGQGTINTVSSGGGGSVGGGS 1 (4) GGGGSQSVLTQPPSASGTSGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYKNNQRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYKAAXDDSLNGPVFGGXTKLTVLGDYKDFEDGDYXDHDIDX XDXDXKAA [SEQ ID NO: 129] MUC- EVQLLESGGGLVQPGGSLRLSCAASGFTFKNYWMSWVRQAPGKGLEWVSDISGGGGTTYIADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIHSGSYYFDYWGQGTLVTVSSGGGGSGGGGSGG 1 (5) GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGADYDVHWYQQLPGTAPKLLIYKNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDXADYYCAVWDDSLNGPXFGGXTKLTVLXDYKXHDGDYKDHDIDX KDDDDKAA [SEQ ID NO: 130] MUC- EVQLLESGGGLVQPGGSLRLSCAASGFTFIKNYWIVISWVRQAPGKGLEWVSDISGGGGTTYIADSVKGRETISRDNSRNTLYLQMNSLRAEDTAVYYCARIHSGSYYFDYWGQGTIATIVSSGGGGSGGG 1 (6) GSGGGGSQSVLTQPPSASGTPGQKVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYKNNQRPSGVPDRFSGSRSGTSASLAISGLRSEDEADYYCAAWDDSLNGPVEGGXXKLTVLXDYXDHDGDYKDF IDIDYKXXDDKAA [SEQ ID NO: 131] MCP- QSVLTQPPSASGTPEQRVTISCTGSSSNIGSDYGVQVVYQQLPGTAPKLLIVSNNQRPSGVPDRESGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGPVEGGGTKLTVLG [SEQ ID NO: 132] 1 (4) MCP- QSVLTQPASASGTPGQRVTISCIGNSSNIGAGYDVHWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLLSEDEADYYCAAWDYSLNGWVEGGGTIKLTVLG [SEQ ID NO: 133] 1 (5) MCP- QSVLTQPSSASGTPGQRVTISCTGNSSNIGAGYDVFIWYQQEPGTAPNLIIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLNGWVEGGGTKLTVLGQ [SEQ ID NO: 134] 1 (6) MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVAYINRGSTYTNYADSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRGYGSGSYYAFDIWGQGTLVTVSSGGGGSGGGGS 1 (7) GGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGSDYGVQWYQQLPGTAPKLLIYSNNQRPSXVPDRFSGSKSGTSASLAISGLRSEDXADYYCAAWDDSLSGPVFGGX [SEQ ID NO: 135] MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMSWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDPDPSGTDAFDFWGQGTLVTVSSGGGGSGGGGSG 1 (8) GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGAGYDVFIVQQQLPETAPKWYGNSNRPSXVPDRFSGSXSEISASLAISGERSEDXADYYCAAWDDSLSAWAFGG [SEQ ID NO: 136] MCP- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYEMNWVRQAPGKGLEWVSAISGPGGSTYYADSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCARDLSDYGDFDYWGQQTLVIVSSGGGESGGGGSGG 1 (9) GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDAHWYQQLPGTAPKWYDNNKRPXXVPDRFSGSXSQISASLAISGLRSEDEADYYCATWDDSLRGWVEG [SEQ ID N0: 137] Cystatin EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYNVINWVRQAPGKGLEWVGLISYDGRTTYYADSVKGRSTISRDNSKNTLYLQTVINSLRAEDTAVYYCATTGTTLDWGQGTLVTVSSGGGGSGGGGSGGGG C (1) SQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPQTAPKWYGNTNRPSXVPDRFSGSXSGISASUISGLBSEDEADYYCAAWDDSLYGWVFGGXTKLTVLGDYXDHDGDYXDHDIDXXDDDDK AA [SEQ ID NO: 138] Cystatin EVQLLESGGGLVQPGGSLRLSCAASGFTESSYSIVINWVRQAPGKGLEWVAFISYDGSNKYYVDSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCARDGVPAVPFDYWGQGTLVTVSSGGGGSGGGGSG C (2) GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGAGYDVHWYQQLPGTAPKWYSNNQRPS [SEQ ID NO: 139] Cystatin EVQLLESGGGLVQPGGSLRLSCAASGFIFSNYAMTWVRQAPGKGLEWVADISHDGFHKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYGRVLPYYYYYGMDVWGQGTLVTVSSGGGGSGGG C (3) GSGGGGSQSVLTQPPSASGTPRQRVTISCIGSSSXIGAGYDVHWYQQLPQTAPKWYGNSNRP [SEQ ID NO: 140] Cystatin EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMNWVRQAPGKGLEWVGLISYDGRITYYADSVKGRSTISRDNSKNTLYLENNSLRAEDTAVYYCATTTGTTLDYWGQGTLVTVSSGGGGSGGGGSGGGGS C (4) QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNTNRPSXVPDRFSGSXSEISXSLAISGLRSXDEADYYCAAWDDSLYGWVEGG [SEQ ID NO: 141] Apo- EVQLLESGGGLVQPGGSLRLSCAASGHTSNNGMHWVRQAPGKGLEWVSAISASGGSTYYADSVKGRFTISRDNISKNTLYLQMNSLRAEDTAVYYCATHGGSSYDAFDIWGQGTLVTVSSGGGGSGGGGSGG A1 (1) GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYVVHWYQQLPGTAPKLLIYG [SEQ ID NO: 142] Apo- EVQLLESGGGLVQPGGSLRLSCAASGFTFRDYYMSWIRQAPGKGLEWVAVTSYDGSKKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDYADDSIAAPAFDIWGQGTLVTVSSGGGGSGGGG A1 (2) SGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSXIGAGYDVHWYQQLPETAPKWYGNSNRPS [SEQ ID NO: 143] Apo- EVXXLESGGGLVQPGGSLRLSCAASGFTERDYYMSWIRQAPGKGLEWVAVTSYDGSKIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDYADDSIAAPAFDIWGQGTINTVSSGGGGSGGG A1 (3) GSGGGGSQSVETQPRSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPETAPKWYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSXDEAXYYCQSYDSSLSVVEGGGTKLTVLXXYXDHDGDYKDHDIDY XDDXXXAXAHHHHHH-SPXXXIRXXXSXXTIHXXXXXXXXDWXXXXXXXXX [SEQ ID NO: 144] Factor EVQLLESGGGEVQPGGSLRLSCAASGFTESSYSMNWVRQAPGKGLEWVAVISYDGRFIYYSDSVKGRFTISRDNSKNTLYLQMNSERAEDTAVYYCARSYGGNLAMDVWGQGTINTVSSGGGGSGGGGSGGG B (2) GSQSNILTQPRSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYDNNKRPSGVPDRFSGSNSGTSASLAISGLRSEDEADYYCAAWDDRLNGRVVEGGXTKETVLGDYXDFIDGDYKDHDIDXK DDDXKAA [SEQ ID NO: 145] Factor EVQLLESGGGLVQPGGSLRLSCAASGFTESSYSMNWVRQAPGKGLEWVAVISYDGSNQYYADSVRGRFTISKDNSKNTLYLQMNSLRAEDTAVYYCAREWHYSLDVWGQGTLYTVSSGGGGSGGGGSGGGGS B (3) QSVLTQPPSASGTPGQRVTISCSGSSSXIGSNTVNWYQQEPGTAPKLLIYRNNQRPSXVPDRFSGSXSGTSASLAIXGLRSEDXADYYCAAWDD [SEQ ID NO: 146] Factor EVQLLESGGGLVQPGGSLRLSCAASGFTFSKHSMNWVRQAPGKGLEWVATVSYDGNYKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGYYYYGMDVWGQGTLVTVSSGGGGSGGGGSGGG B (4) GSQSVLTQPPSASGTPGQRVTISCTGSSSNIGNNAVNWYQQLPGTAPKEIIYNNNQRPXXVPDRFSGSXSGTSXSLAISGLRSEDEADYYCQPYXDXLSSNIVEGGXTXLTVLXDXXDHDXXYKDHDIXYXD XDXXXXAHHHHHH-SPRWPIRPIVSXIXIXWXXVLXRXXXXNXXXXXXXXXXXXHXXXXXX [SEQ ID NO: 147] C1 inh. EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNRGNWGTYYFDYWGQGTLVTVSSGGGGSGGGGS (2) GGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVSWYQQLPGTAPKWYGSSNRPSGVPDRESGSXSGTSASLAISGLRSEDEADYYCCISYDSSLSDFIVVEGGXTKLTVLXDYXDFIDGDYKDHD IDXXDDDDXAA [SEQ ID NO: 148] C1 inh. EVQLLESGGGEVQPGGSLRLSCAASGFTESNAWMSWVRQAPGKGLEWVSAISGSGGSTYYADSNIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNRGNWGTYYFDYWGQGTIAMISSGGGGSGGGG (3) SGGGGSQSVETQPRSASGTPGQRVTISCSGSSSXIGSNYVSWYQQLPGTAPKLLIYGSSNRPSXVPDRESGSXSGTSASLAISGLRSEDXADYYQRSYDSSLSDFIVVEGGXTKLTVLGDYXDHDGDYKDF IDXDXXDDXXXAA [SEQ ID NO: 149] C1 inh. EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNRGNWGTYYFDYWGQGTLVTVSSGGGGSGGGGS (4) GGGGSQSVLTQPPSASGTPGQRVTISCSGSSSXIGSNYVSWYQRLPGTAPKWYGSSNRPSXVPDRESGXXSGTSASLAISGLRSEDEADYYCQSYDSSLSXHVVEGGXTKLTVL [SEQ ID NO: 150] C5 (3) EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYGMHWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCLTLGGYWGQGTIATTVSSGGGGSGGGGSGGGGSQS VLIQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLUYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSXDEADYYCQSYDSSLSGWVEGGXTKLTVLXDYKXHDGDYKDHDIDXKDDDXXA A [SEQ ID NO: 151] C4 (2) EVQLLESGGGLVQPGGSLRLSCAASGFTESDYYMSWVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGYGSGSRATGYNWEAPWGQGTLVTVSSGGGGSGG GGSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSXSGTSXSLAISGLRSEDXADYYCQSYDSSLXGPYWVFXXXNQXDGPRXXXKTMTXX XXXXDIDYXXXXXQXRXAXXXHHH-SPXXP [SEQ ID NO: 152] C4 (3) EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAWYCARGINSTSSFDYWGQGTIATIVSSGGGGSGGGGSGG GGSQSVLTQPPSASGTPGQRVTISCSGSSSXIGNHYVSWYQQLPGTATKLLIYXDDLLPSXVPDRFSGSXSGTSASLAIXGLRSEDEADYYCAAWDDRSGQVIIGGXTKLTVLGDYXDHDGDYXDHDIDXX DDDXKAXAHHHHHH-XXRWPIRPXVSXXTIHXXXFXXXXXXKT [SEQ ID NO: 153] C4 (4) EVQLLESGGGLVQPGGSLRLSCAASGFTESSYSMNWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAWYCAKHSGYGFDIWGQGTLVTVSSGGGGSGGGGSGGGG SQSVLIQPPSASGTPGQRVTISCSGGASXIGMHEVSWYQQLPGTAPKWYYDDLLPSGVPDRFSGXXSGTSASLAISGLRSEDEADYYCAAWDDSLNGWVEGGXTKLXVLGDYXDXXGDYKDHDIDXKDXX XXAXAHXHHHH-SPXWXXRPIVXXITXXXXVXLQRXDWXXPXVXXXXXXXXXXPX [SEQ ID NO: 154] C3 (3) EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMNWVRQAPGKGLEWVANINQDGSTKEYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDTGGNYLGGYYYYGIVIDVWGQGTEVIVSSGG GGSGGGGSGGGGSQSVLIQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYRNDQRPSXVPDRFSGSXSGTSASLAISGLRSXDXADYYCSSYAGNNNLVEGGXTKLTVLGDYXDHDG DYKDHDIDYXDXDXXAA [SEQ ID NO: 155] C3 (4) EVQLLESGGGLVQPGGSLRLSCAASGFTESDHYMDWVRQAPGKGLEWVSGISGNGATIDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARPSITAAGSEDAFDLWGQGTLVTVSSGGGGSGG GGSGGGGSQSVLIQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSETSASLAISGLRSXDGADYYCQSYDSSLSGWVEGGXTKLTVLGXYXDHDGDYKD XDIDYKDDXXKAA [SEQ ID NO: 156] C3 (5) EVQLLESGGGLVQPGGSLRLSCAASGFIESNYWIVISWVRQAPGKGLEWVSGISGSGGTTYYADFVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARKYYYGSSGAFDIWGQGTLVIVSSGGGGSGG GGSGGGGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLLIYRNNQRPSXVPDRFSGSXSGTSASLAIXGLRSEDXADYYCAAWDDSLXGPVFXGKIKLTVL [SEQ ID NO: 157] C3 (6) EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVANINQDGSTKEYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDTGGNYLGGYYYYGMDVWGQGTENTVSSGGG GSGGGGSGGGGSIRSVLTQPPSASGTPGQRVIISCSGSSSNIGSNYVYWYQQLPGTAPKWYRNDQRPSGVPDRFSGSXSGTSASLAISGLRSEDXADYYCSSYAGNNNLVFGGXXKLIVLGXXXDHDGD YKDHDIDXXDXDXXAA [SEQ ID NO: 158] MYO EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVVAGSWGQGTLVTVSSGGGGSGGGGSGGGG M2 SQSVLTQPPSASGTPGQRVTISCSGSSSXIGNNAVNWYQQLPGIAPKWYDNNKRPSXVPDRFSGXXSGTSXSLAIXGLRSEDEADYYCA [SEQ ID NO: 159] (1) MYO EVQLLESGGGLVQPGGSLRLSCAASGFTFSNEWMAWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYKAGTYHDFWSATYWGQGTLVTVSSGGGGSGGGGSG M2 GGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYGNSNRPSXVPDRFSGSXSGTSASLAISGLRSEDXADYYCAAWDDSLNGWVFGGXTKLTVLGD (2) [SEQ ID NO: 160] LUM EVQLLESGGGLVIRPGGSLRLSCAASGHTSSNYMSWVRQAPGKGLEWVSAISASGTYTMDSVNGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVNTVGLGTPEDNWGQGTLVTVSSGGGGSGGGGS GGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSIVIVNWYQQLPGTAPKLLIYGNRNRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYYCAAWDDSLSGWVEGGKIKLTVLXDYXDHDGDYKD HDIDXXXDDXXAA [SEQ ID NO: 161] DUSP9 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYGFHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGEFGVYWGQGTLVTVSSGGGGSGGGGSGGGG SQSVETQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKWYGNRNRPSGVPDRFSGSXSGTSASLAISGLRSEDEADYYCSSYAGSNMFEVVEGGXTKLTVLGDYXDHDGDYKDHDIDYKD DDXKAA [SEQ ID NO: 162] CHX10 EVQLLESGGGLVQPGGSLRLSCAASGFTESSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNSDYYGMDVWGQGTEMTVSSGGGGSGGGGSGGG (1) GSQSVLTQPPSASGTPGQRVTISCSGSSSNIGYSDVYWYQQLPGTAPKLLIYENNKRPSXVPDRFSGSXSGTSASLAISGLRSEDEADYYCSTWDDSLNGHVIFGG [SEQ ID NO: 163] CHX10 EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMSWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQNINSLRAEDTAVYYCARNYGDSINWFDPINGQGTIATIVSSGGGGSGGG (3) GSGGGGSQSVETQPPSASGTPGQRVTISCSGSSSXIRSNTVNWYQQLPGTAPIKLINGNSNRPSXVPDRFSGXXSGTSXSLAISGLRSEDXADYYCAXWDDSLN [SEQ ID NO: 164] ATP- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMHWVRQAPGKGLEWVAVISYDGSKTYHADSVEGRFTISRDNSKIITLYLQMNSLRAEDTAVYYCARHLRPYYFDYWGQGTLYTVSSGGGGSGGGGSG 5B (1) GGGSQSVLTQPPSASETPGQRVTISCSGSSSXIGSNTVNWYQQLPGTAPMINGNSNRPSXVPDRESGXXSGTSASLAISGLRSEDXADYYCSAWDDRLRGRVEGG [SEQ ID NO: 165] ATP- EVQLLESGGGLVQPGGSLRLSCAASGETESSYGMHWVRQAPGKGLEWVSLISSASSYIYHADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARAGRVCTNGVCHTTEDYWGQGTLVTVSSGGGGSG 5B (2) GGGSGGGGSQSVLIQPPSASGTPGQRVTISCSGDRSNIGSNTVNWYQQLPGTAPKLLIYGNSNRPSGVPXRFSGSXSGTSXSLAISGLRSEDEADYYCQSYDSSLSAVVEGGXTKLTVLGDYXXHDXXYKD HDIDYXXDXDXAXAHXHHHH-SPRXXXXPIVSXXXXXXXXXXXXXXLXKXXXXPTXXXXXXXX [SEQ ID NO: 166] ATP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKGLEWVSSISSTSTYIHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVSSWYSAFDIWGQGTLVIVSSGGGGSGGGGSGG 5B (3) GGSQSVLTQPPSASGTPGQRVTISCTGSSSNIGNNAVNVQQQLPGTAPKLLIYSNNQRPSXVPDRESGSXSGTSASLAISGLRSEDXADYYCQSYDSSLSGVIFGGXIKLXVLXDYXDHDGDYXDHDIDXX XDDDKAA [SEQ ID NO: 167] Sox11a EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFWMSWVRQAPGKGLEWVSSISGGGGTAFYVDSVKGRETISRDNSKNTLYLQMNSLRAEDTALYYCARMTDLESGDAFDIWGQGTLVTVSSGGGGSGGGGS GGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVNWYQQLPGTAPKLLIYNDNVRPSGVPDRFSGSXSGTSASLAISGLRSEDXADYYCQXWGTGVEGGXIKLIVLXDYXDHDGDXXDHDIDXKDX DXKAA [SEQ ID NO: 168] TBC1 EVQLLESGGGEVQPGGSLRLSCAASGFTFSSYSMSWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRTRGSTALDIWGQGTLVINISSGGGESGGGGS D9 (1) GGGESQSVCIQPPSASGTPGQRVTISCSGSSSYIGSNYVYWYQQLPGTAPKWYRNNQRPXXVPDRFSGXXSGTSASLAISGLRSEDEADYYCAAVVDDSLSGWVFGGXTKLTVLGD [SEQ ID NO: 169] UPF3B EVQLLESGGGINQPGGSLRLSCAASGETESDYYMTWIRQAPGKGLEVINSDISWNGSRTHYADSVKGRFTISRDNSMILYLQNINSLRAEDTAVYYCSSHLVYINGQGTIATIVSSGGGESGGGGSGGGES (1) CISVCIQPPSASGTPGQRVIISCTGSSSNIGAGYDVHWYQQLPGTAPKELIYDNNKRPSXVPDRESGSXSGTSASLAIXGLRSEXXADYYCQTYDSSLSGSWFGEXTKETVLGDYXDHDXDY [SEQ ID NO: 170] UPF3B EVQLLESGGGLVQPGGSLRLSCAASGETESSYAMSWVRQAPGKGLEWVSYISSSSSYANYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAREGVYSGTYLFAFDIWGQGTLVIVSSGGGGSGGG (2) GSGGGESCISVLTQPPSASGTPGQRVTISCTGSSSXIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSXVPDRFSGSXSGTSASLAISGLRSXDEADYYCQSRDSSESGWVFGGXTKLTVLGD [SEQ ID NO: 171] Apo- EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSGVSWNGSRTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVAYDIDAFDMWGQGTLVTVSSGGGG A4 (1) [SEQ ID NO: 172] Apo- EVQLLESGGGLVIRPGGSLRLSCAASGETESDYYMSVVVRQAPGKGLEWVSGVSWNGSRTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVWCARVAYDIDAFDMWGQGTLVTVSSGGGGSGGGGSG A4 (2) GGGSQSVLTQPPSASGTPGQRVTISCSGSFSNIGSNYVYWYQQLPGTAPKLLEYENNKRPSGVPDRESGSXSGISASLAISGERSEDEADYYCAAWDDSLNGPMFGGXTKLTVLXDYKDHDGDYKDHDIDYK DDXXXXAAHHHHHH-SPRWXIRPXXSXXTIHXXXXLXXXD [SEQ ID NO: 173] Apo- EVQLLESGGGENQPGGSLRLSCAASGFTFSSYSNINVIVRQAPGKGLEWVSAITGSGNATHADSVKGRIMSRDNSKNITLYLQMNSLRAEDTAVYYCITGATTRWGQGTLVTVSSGGGGSGGGGSGGGGSQ A4 (3) SVLTQPPSASGTPGQRVTISCSGSRSNIGSNHVFWYQQLPGIAPKWYENNKRPSGVPDRFSESXSGTSASLAISGLRSEDXADYKAAWDDSLSGWVFGG [SEQ ID NO: 174] TBC1D9 EVQLLESGGGLVIRPGGSLRLSCAASGETESNAVVMS4VVRQAPGKGLEVVVSFISSSSSYNYADSVKGRETISRDNSKNTLYLIRMNSLRAEDTAVYYCARVNBIGCTNGVCNGHDYWGQGTLVTVSSGG (2) GGSGGGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSXIGSNTVNIWYCIQLPGTAPKWYDNNKRP [SEQ ID NO: 175] TBC1D9 EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMSWVRQAPGKGLEMSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGRTMASHWGQGTINTNISSGGGGSGGGGSGGGGS (3) QSVETQPPSASGTPGQRVTISCSGSSSXIGNNHVSWYQQLPGTAPKEINGNSNRPSXVPDRFSGSXSGTSASLAISGLRSEDXADYYCAAWDNSEKVWMFGG [SEQ ID NO: 176] ORP-3 EVQLLESGGGINQPGGSLRLSCAASGETESSNYMSWVRQAPGKGERANSYISGNSGYTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHAGSYD MYG NADVWGQGTLAITVSSGGGGS (1) GGGESGGGGSQSVLTQPPSASGTPGQRVTISCSGSTSXIGSHYVYVVYQQIPGTAPKIIIYGNSNRPXXVPDRFSGXXSGTSXSLAISGLRSEDXADYYCQSYDSRLSGMFGG [SEQ ID NO: 177] ORP-3 EVQLLESGGGEVQPGGSLRLSCAASGETESSYAMHINVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTENLQMNSLRAEDTAWYCARKSSLDVWGQGTINTVSSGGGGSGGGGSGGGGS (2) QSVLTQPPSASGTPGQRVIISCSGSSSXIGNNYVSWYQQLPGTAPKELIYDDNKRPSGVPDRFSGSXSDTSASLAISGLRSEDEADYYCAAWDDSLXGRVFGGXTKLTVEG [SEQ ID NO: 178] CIMS EVXLIESGGGLVQPGGSLRLSCAASGETESDHYMDWVRQAPGKGLEMSGISGSGGSTYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASRLYWGQGTLVTVSSGGGGSGGGGSGGGGSQSVL (5) TQPPSASGTPGQRVTISCTGSSSNIGAGYVVHMQQLPGTAPKLINDNDKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSEDAVLFGGXXKLTVLGEQKLISEXDLSGSAA [SEQ ID NO: 179] CIMS EVQLLESGGGLVQPGGSLRLSCAASGETESSYNVISWVRQAPGKGLEMSAISGSGGRTYYTDSVRDRETISRDNSKNTLYLQMNSLRAEDTAVYYCARDLMPVCQYCYGMDVWGQGTINTVSSGGGGSGG (13) GGSGGGGSCISVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKWYSNNQRPSGVPDRESGSXSGTSASLAISGLRSEDEADYXCQSYDSSIAKDVVEGGXTKLTVLGEQKLISKXDL SGSAXAHHHHHH-SPRXPIRPIVSRXTIHWXXXLXXXDWENXXXTXLXXXAXXPPFXXXXX [SEQ ID NO: 180] PKB EVQLLESGGGLVQPGGSLRLSCAASGETEGSSYMSWVRQAPGKGLEWVSSESSGGSYTYYADSVKGRETISRDNSKNTLYLQJVINSLRAEDTAVYKARYHASWGRYLDYWGQGTLVIVSSGGGESGGGG gamma SGGGGSDIQMTQSPSSESASVGDRVTITCRASQSISSYLNWYQQKPGKAPKEIIYAASSLQSGVPSRFSGSGSGTDFTETISSLQPEDFATYYCQQVSSWESTFGQGTKLEIKRLGDYKDHDGDYKDHDI (1) DYKDDDDKAAAHHHHHH* [SEQ ID NO: 181] PKB EVQLLESGGGEVQPGGSLRLSCAASGETESYSGMGWVRQAPGKGEWVSYISSGSYYTGYADSVKGRFTISRDNSINTLYLQMNSERAEDTAWYCARYSGWRHGFDYWGQGTLVIVSSGGGGSGGGGSGGG gamma GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQISGVPSRFSGSGSGTDETLTISSLQPEDFATYYCQQATVSPSTFGQGTKLEIKRLGDYKDFIDGDYKDHDIDY (2) KDDDDKAAAHHHHHH* [SEQ ID NO: 182] BTK EVQLLESGGGLVQPGGSLRLSCAASGETEGSYYMGWVRQAPGKGLEVVVSSIGSGYYSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGPYWWGLDYWGQGTLVIVSSGGGGSGGGGSG (2) GGGSDIQNATQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKEINAASSLQSGVPSRFSGSGSGTDFTETISSLQPEDFATYYCQQWFYHGPHTFGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 183] BTK EVQLLESGGGLVIRPGGSLRLSCAASGETESSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLIRMNSLRAEDTAVYYCARGYYGMDYWGQGTLVTVSSGGGGSGGGGSGG (3) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGIDFILTISSLQPEDFATYYCQQTWYLPTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 184] BTK EVQLLESGGGENQPGGSLRLSCAASGFTFSSYAMS4VVRQAPGKGLEVVVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGYYGLDYWGQGTLVTVSSGGGGSGGGGSGG (4) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRESGSGSGTDFTLTISSLQPEDFATYYCQQSGAVPRITGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 185] CDK-2 EVQLLESGGGINCIPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEVINSGISSYYGYTYYADSVKGRFTISRDNSKNTLYEQMNSLRAEDTAVYYCARNIYGYYMDYVVGQGTINTVSSGGGGSGGGG (1) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASIRSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSSLYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 186] CDK-2 EVQLLESGGGEVQPGGSLRLSCAASGFTFGSSYMGWVRQAPGKGEWVSSIYGSSSYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWYWSWSSFDYWGQGTLVTVSSGGGGSGGGGSGG (2) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSEVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGGINPYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 187] GM- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYGMSWVRQAPGKGLEWVSYEGSGYYYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYFDYWGQGTLVTVSSGGGGSGGGGSGGGGS CSF DEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYFELPTEGIRGTKLEEKRLGDYKDHDGDYKDFIDIDYKD (4) DDDKAAAHHHHHH* [SEQ ID NO: 188] GM- EVCILLESGGGLVQPGGSLRLSCAASGFTEGSGYMYVVVRQAPGKGLEWVSSISSSYGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVVYPSNYFDYWGQGTENTVSSGGGGSGGG CSF GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATWQRQGYPWWWGPYTFGQGTKLEIKRLGDYKDHDGDYKD (5) HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 189] GM- EVQLLESGGGEVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSERAEDTAVYYCARYYSGSWGHYFDYWGQGTLVTVSSGGGGSGGGG CSF SGGGGSDIQMTQSPSSESASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLIRSGVPSRFSGSGSGTDETLTISSLQPEDFATYYCQQVFSNPLTFGQGTKLElKRLGDYKDHDGDYKDHD (6) IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 190] FASN EVQLLESGGGLVQPGGSLRLSCAASGFTEGYSGMSWVRQAPGKGLEWVSYIGGGYGSTSYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARWSWHHGSYTMDYWGQGTLVTVSSGGGGSGGGG (1) SGGGGSDIQMTQSPSSESASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSWELPTEGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 191] FASN EVQLLESGGGEVQPGGSLRLSCAASGFIFSGSSIVISWVRQAPGKGLEWVSSIYYGSGYTYYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARGTYLDYWGQGTEVIVSSGGGGSGGGGSGGG (2) GSDIQMIQSPSSLSASVGDRVIETCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHTWWSSYLHTFGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 192] FASN EVQLLESGGGLVQPGGSLRLSCAASGFIFYGYSMGWVRQAPGKGLEWVSSISYSGGYTYYADSVKGRFTISRDNSKNTLYEQMNSLRAEDTAVYYCARWSHVDSGALDYWGQGTLVTVSSGGGGSGGGGS (3) GGGGSDIQIVITQSPSSESASVGDRVTITCRASQSISSYLNVQQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTINTLTESSEQPEDFATYYCQQYWYTYWLPTEGQGTKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 193] FASN EVQLLESGGGLVQPGGSLRLSCAASGFIFSGSGMSWVRQAPGKGLEWVSYIGSYYGGTYYADSVEKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARAFVNGVGGWGPYFDYWGQGTLVTVSSGGGGS (4) GGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSESSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTESSLQPEDFATYYCQQSFFPPYTFGQGTKLEIKRLGDYKDHDGDYK DHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 194] GAK EVQLLESGGGLVQPGGSLRLSCAASGFTFGSSYMSWVRQAPGKGLEWVSSESSSSYGTYYADSVKGRETISRDNSKNTLYLIRMNSLRAEDTAVYYCARNPGFDYWGQGTLVTVSSGGGGSGGGGSGGGG (1) SDIQMTQSPSSLSASVGDRVTETCRASQSESSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSGIDFILTISSLQPEDFATYYCQQHYWLPTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDD DKAAAHHHHHH* [SEQ ID NO: 195] GAK EVQLLESGGGLVIRPGGSLRLSCAASGHTGGGGMSWVRQAPGKGLEWVSSESSSGYGMADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARWGWSYLDYWGQGTLVTVSSGGGGSGGGGSGGGGS (2) DDIQMTQSPSSLSASVGRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYYPLYTEGQGTKLEIKRLGDYKDFEDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 196] GAK EVQLLESGGGLVQPGGSLRLSCAASGFTFGSSYMSWVRQAPGKGLEWVSGISSSGYGTYYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARGYYHYGYAGFYFDYWGQGTEVFVSSGGGGSGG (3) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSESSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSGTDETLTESSLQPEDFATYYCQRSAYLFTEGQGTKLEIKRLGDYKDFEDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 197] HADH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMSWVRQAPGKGLEWVSSESSGGYGTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYGWGPLDYWGQGTLVTVSSGGGGSGGGGSGGG 2 (1) GSDEQEVTTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTESSEQPEDFATYYCQQGYNWPYTEGQGTKLEEKREGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 198] HADH EVQLLESGGGEVQPGGSLRLSCAASGFIFSGSYMSWVRQAPGKGLEWVSSISGGSYYTSYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARWSENVVAHHWLDYWGQGTLVTVSSGGGGSGGGG 2 (2) SGGGGSDEQEVTIQSPSSLSASVGDRVTITCRASQSESSYLNWYQQKPGKAPKILEYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYYAPYTEGQGTKLEIKRLGDYKDHDGDYKDHD IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 199] HADH RVQLLESGGGLVQPGGSLRLSCAASGFTFGSSYMSWVRQAPGKGLEWVSSESSYGYYTGYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARSYGSWYFDYWGQGTLVTVSSGGGGSGGGGSGGG 2 (3) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTESSLQPEDFATYYCQQGFVGPSTFGQGTKLEEKRLGDYKDHDGDYKDHDEDYKDD DDKAAAHHHHHH* [SEQ ID NO: 200] HADH EVQLLESGGGLVQPGGSLRLSCAASGFTEGGSYMSWVRQAPGKGLEWVSSISGGSYYTSYADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCARWSPPSYSYGESYYRYFDYWGQGILVTVSSGGGG 2 (4) SSGGGGSGGGGSDIQMTQSPSLSASVGDRVTETCRASQSESSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSETDFTLTESSLQPEDFATYYCQQSYPPSTFGQGTKLEIKRLGDYKDHDGDYKD HDEDYKDDDDKAAAHHHHHH* [SEQ ID NO: 201] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGFTFGYSYMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETESRDNSKNTLYLQMNSLRAEDTAVYYCARYHASYPSWWYEDYWGQGTLVFVSSGGGGSGGGG (5) SGGGGSDEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSGTDETLTESSLQPEDFATYYCQQVWHGLHTTGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 202] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGHTGSSSMSWVRQAPGKGLEWVSSISYGSSSTSYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARGGYGFDYWGQGTLVTVSSGGGGSGGGGSGGGGSD (6) EQMTQSPSSLSASVGDRVTITCRASQSESSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSGTDFTLTESSLIRPEDFATYYCQQGGYWPLTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHH* [SEQ ID NO: 203] IL-6 EVQLLESGGGLVQPGGSLRLSCAASGFTFGYSSMGWVRQAPGKGLEWVSGISSYGYGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYHSGWGMDYWGQGTLVTVSSGGGGSGGGGSGGG (7) GSDIQMTQSPSSLSASVGDRVTITCRASQSESSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFAYLFETEGQGTKLEIKRLGDYKDHDGDYKDFEDEDYK DDDDKAAAHHHHHH* [SEQ ID NO: 204] IL-6 EVCILLESGGGLVQPGGSLRLSCAASGFTESGYGMSWVRQAPGKGLEWVSSISSSSSYTYYADSVKGRFTISRDNSKNTLYLQMNSERAEDTAVYYCARYGWGYFDYWGQGTENTVSSGGGGSGGGGSGGG (8) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSYYPPTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 205] Keratin EVQLLESGGGEVQPGGSLRLSCAASGFTEGYYYMYWVRQAPGKGLEWVSSIGSSGSSISYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARGHAFFDYWGQGTEVIVSSGGGGSGGGGSGGGGS 19 (1) DIQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVWYWPPTEGQGTKLEXKRLXDYKDHDGDYKXHDIDYKDDDD KAA [SEQ ID NO: 206] Keratin EVQLLESGGGEVQPGGSLRLSCAASGFTFYGSSMSWVRQAPGKGLEWVSYIGSDSSYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYWSVFDYWGQGTINTVSSGGGGSGGGGSGGGG 19 (2) SDIQMTQSPSSLSASNIGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDETLTISSLQPEDFATYYQRQSYWSWLPTEGQGXKLEIKREADYKDHDGDYKDHDIDYKDDD DKAA [SEQ ID NO: 207] Keratin EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWGGWWLDYWGQGTLVIVSSGGGGSGGGGSGGGG 19 SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWWSYYGALFTFGXGTKLX1KRLXDYKDHDGDYKDHDEDYK (3) GDDDDXXPPIIIIIIDHRXXX1XPIVSXXXRAHWXXFXXXXXXKX [SEQ ID NO: 208] KSYK EVQLLESGGGEVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGISSGYYYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGWYWNGLDYWGQGTENTVSSGGGGSGGGGSGG (1) GGSDEQMTQSPSSLSASVGDRVTITCRASQSESSYLAWYQQKPGKAPKILEYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSNILPTFGQGTKLEIKRILDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 209] KSYK EVQLLESGGGINQPGGSLRLSCAASGETESSYAMSWVRQAPGKGLEVINSAISGSGGSTYYADSVKGRFTISRDNSKNTLY1QMNSLRAEDTAVYYCARGYYGLDYWGQGRAITVSSGGGGSGGGGSGGGG (2) SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSGAVPPTFGQGTKLElKRLGDYKDHDGDYKDHDIDYKDDD DKAAAHHHHHH* [SEQ ID NO: 210] MATK EVQLLESGGGLVQPGGSLRLSCAASGETEGSSYMGWVRQAPGKGLEWVSGIGGYGYYTGYADSVKGRFIESRDNSKNTLYLQMNSLRAEDTAVYYCARYDWGHSPGSWYYGSFDYWGQGTLVTVSSGGGGS (1) GGGGSGGGGSQSVETQPPSASGTPGQRVIESCSGSSSNIGSSYVYWYQQLPGTAPKWYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWAGAYHSHVVFGGETKLIVLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 211] MATK PAILLESGGGINQPGGSLRLSCAASGETFYGYSMYWVRQAPGKGLEVVVSYIGSYSGSTSYADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCARYYHYYHTWLDYWGQGTLVIVSSGGGGSGGGGS (2) GGGGSDIQNATQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGFYPFTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 212] MATK EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLIRMNSLRAEDTAVYYCARYPEYDYSVVGGRWPSYGIDYWGRGTENTVSSG (3) GGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKELIYAASSLQSGVPSRESGSGSGTDFTLTISSLQPEDFATYYCQQWNSGMLKIFGQGTKLEIKREGDYKDHD HDGDYKDEDYKDDDDKAAAHHHHHH* [SEQ ID NO: 213] MAPK- EVQLLESGGGEVQPGGSLRLSCAASGFTFSGSGMYWVRQAPGKGLEWVSYESGSGSYTDYADSNIKGRFTISRDNSKNTLYEQMNSLRAEDTAVYYCARSGSFDYWGQGTINTVSSGGGGSGGGGSGGGGS 1 (1) IDIQMTQSPSSLSASVGDRVTTCRASQSISSYLNJWYQQKPGKAPKLLIYAASSLIRSGVPSRFSGSGSGTDFTLT1SSLQPEDFATYYCQQVSSSLYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 214] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGFTFSYGDMSWVRQAPGKGLEMSGESSGGSSTYYADSVKGRFTISRDNSKNTLYLQNANSLRAEDTAVYYCARGYGYAWYFDYVVGQGTINTVSSGGGGSGGGGSG 1 (2) GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDETLTISSLQPEDFATYYCQQWWHPYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDD DKAAAHHHHHH* [SEQ ID NO: 215] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGETESYSYMYVVVRQAPGKGEDANSSISSGGDYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNFWEDYWGQGTINTVSSGGGGSGGGGSGGGGS 1 (3) DEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASGLYTFGQGTKLEIKRELDYKDHDGDYKDHDEDYKDDDDK AAAHHHHHH* [SEQ ID NO: 216] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGETESYSSMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAWYCARHYPEYWFDYINGQGTINTVSSGGGGSGGGGSGGG 1 (4) GSDIQMTQSPSSESASVGDRVTITCRASQSISSYLNVQQQKPGKAPKLEIYAASSLQSGVPSRFSGSGSGTINTLTISSEQPEDFATYYCQQGGSWAYPLTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 217] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGETEGYGGMSVVVRQAPGKGLEWVSSEYGSSSSTYYADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCARHWRSVYFDYWGQGTLVTVSSGGGGSGGGGSGG 8 (1) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLIIYAASSEQSGVPSRFSGSGSGTDFTLT1SSLQPEDFATYYCQQGWGSPLTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 218] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGETESGSYMSWVRQAPGKGLEWVSSEYGYSSYTYYADSVKGRFIESRDNSKNTLYLQMNSLRAEDTAVYYCARGSYLDYWGQGTLVTVSSGGGGSGGGGSGGGGSD 8 (2) IQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGINTLTISSLQPEDFATYYCQQYWYPYTEGQGTKLEIKRLGDYKDHDGDYKDHDiDYKDDDDKAA AHHHHHH* [SEQ ID NO: 219] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGFTFGYYSMSWVRQAPGKGLEWVSSISSSSSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVWCARHYSSFDYVVGQGTENTVSSGGGGSGGGGSGGGGS 8 (3) DIQMTQSPSSLSASVGDMITITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLIESSLQPEDFATYYCQQSYWYPFTFGQGTKLEEKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHH* [SEQ ID NO: 220] Osteo- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAYSWEDYWGQGTLVTVSSGGGGSGGGGSGGGGS pontin DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKELIYAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFATYYMQVAGYYHYPFTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDD (1) DDKAAAHHHHHH* [SEQ ID NO: 221] Osteo- EVQLLESGGGLVIRPGGSLRLSCAASGETESSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLIRMNSLRAEDTAVYYCARYHYNYYMDYVVGQGTLVTVSSGGGGSGGGGS pontin GGGGSDEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSYLLIFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDD (2) DDKAAAHHHHHH* [SEQ ID NO: 222] Osteo- EVQLLESGGGLVQPGGSLRLSCAASGETESSYAMSVVVRQAPGKGLEVVVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSERAEDTAVYYCARAYSWEDYWGQGTLVTVSSGGGGSGGGGSGGG pontin GSDIQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKELIYAASSLQSGVPSRFSGSGSGTDRLTISSLQPEDFATYYMQVISGGHWPFIFGQGIKLEIKRLGDYKDHDIDYKDHDIDYKD (3) KDDDAAAHHHHHH* [SEQ ID NO: 223] P85A EVQLLESGGGLVQPGGSLRLSCAASGFTFYSSSMSWVRQAPGKGLEVVVSGISSSYSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVWCARYSSYGSFDYVVGQGTLVTVSSGGGGSGGGGSGG (1) GGSDIQMTIRSPSSLSASVGDRVTITCRASQSESSYLNWYQQKPGKAPKLLEYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSAFPSTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 224] P85A EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMGWVRQAPGKGLEWVSYIGYSSGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRYSYFDYWGQGTINTVSSGGGGSGGGGSGGGG (2) SDIQMTQSPSSLSASNIGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRESGSGSGTNTLTISSLQPEDFATYYQRQWSYGPLTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDD DKAAAHHHHHH* [SEQ ID NO: 225] P85A EVQLLESGGGLVQPGGSLRLSCAASGRIFSSYAMSWVRQAPGKGLEWVSGISSGYYYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAWYCARNGAGSYSWFDYWEQGTLVTVSSGGGGSGGGGSGG (3) VGGSDIQMTQSPSSLSASGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSSVWPFTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 226] PTK6 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEVINSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQNINSLRAEDTAVYYCARGGHGLDYWGQGTEMTVSSGGGGSGGGGSGGG VGSDIQMTQSPSSISASVGDRTITCRASQSESSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDETLTISSLQYEDFATYYCQQGSDVPFTEGQGTKLEIKRLGDYKDHDGDYKDHDEDYKDDDD KAAAHHHHHH* [SEQ ID NO: 227] PTPN EVQLLESGGGLVQPGGSLRLSCAASGFTFGYSSMSWVRQAPGKGLEMSSISYSGSGTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYKARGWYPHPGHWYIDYWGQGTLVTVSSGGGGSGGGGSG 1 (1) GGGSDEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAPNCQQHFSLPTFGQGTKLEIKREGDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 228] PTPN EVQLLESGGGLVQPGGSLRLSCAASGFTFYSYGMYWVRQAPGKGLEVVVSAISGSGGSTYYADSVKGRFTISRDNSKNILYLQMNSLRAEDTAVYYCARGGYYAHYAFDYWGQGTLVTVSSGGGGSGGGGS 1 (2) GGGGSDIQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLT1SSLQPEDFATYYCQQSSTPHTGQGTKLEIKRLGDYKDHDGDVKDIIDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 229] PTPN EVQLLESGGGLVQPGGSLRLSCAASGFTFSYYSMSWVRQAPGKGLEWVSSESSSGGGTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWFSSAFDYWGQGTLVTVSSGGGGSGGGGSGGGG 1 (3) SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLEYAASSLCISGVPSRFSGSGSGIDFILTISSLQPEDFATYYMQGVPPYTEGQGTKLEIKRLGDYKDHDGDYKDHD1DYKDDDD AKAAHHHHHH* [SEQ ID NO: 230] RPS6K EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARRYSGYEDYWGQGTENTVSSGGGGSGGGGSGGGG A2 (1) VSDIQMTQSPSSLSASVGDRTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDETLTISSLQPEDFATYYQRQNWWGLPTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDD ADKAAHHHHHH* [SEQ ID NO: 231] RPS6K EVQLLESGGGLVQPGGSLRLSCAASGFTFYGSYMYWVRQAPGKGLEWVSGISPYSSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGFPFIDYWGQGTIAMISSGGGGSGGGGSGGGGS A2 (2) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTESSLIRPEDFATYYCQQNGVGLITEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDD DKAAAHHHHHH* [SEQ ID NO: 232] RPS6K EVQLLESGGGLVQPGGSLRLSCAASGRIFYGYGMSVAIRQAPGKGLEWVSGISGGSGSTGYADSVKGRFTISRDNSKNTLYLQMNSERAEDTAWYCARGYEIYARSSNEPSMDYWGQGTLVSSGGGGSGGG A2 (3) GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSMSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYWWGLFTEGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 233] STAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTESGYSMGYVVRQAPGKGLEMSGISSYYYGTSYADSVKGRFTISRDNSKNTLYLQMNSERAEDTAVYYCARSWTVGSSINDGDAFDYWGQGTLVIVSSGGGGSG (1) GGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYWYPLTFGQGTKLEIKRLGDYKDHDGDYKDH D1DYKDDDDKAAAHHHHHH* [SEQ ID NO: 234] STAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFYGGSMYWVRQAPGKGLEMSSISSGGSYTYYADSVKGRFTISRDNSKNTLYLQNINSLRAEDTAVYYCARVGYDTMDYWGQGTLVIVSSGGGGSGGGGSGGGG (2) SDIQNATQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYMQRWYWVQLFITGQGTKLEIKREGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 235] STAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTEGYYGNIGWVRQAPGKGLEWVSSFYSGYGSTSYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYKARAAWSGYMDYWGQGTLVTVSSGGGGSGGGGSGGG (3) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLEYAASSLCISGVPSRFSGSGSGIDFILTISSLQPEDFATYYMQYSHYLLTFGQGTKLEIKRLGDYKDHDGDYKDHDiDYKDD DDKAAAHHHHHH* [SEQ ID NO: 236] STAP2 EVQLLESGGGLVQPGGSLRLSCAASGHTYYGGMSWVRCIAPGKGLEWVSSIYYSSGSTSVADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYKARHGWDDNGFDYWGQGTLVTVSSGGGGSGGGGSGGG (4) GSDIQMTCQSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFATYYCQQVYSYLETEGQGTKLEIKRLGDYKDHDGDYKDFIDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 237] STAT1 EVQLLESGGGLVQPGGSLRLSCAASGFTFGYYGMSWVRQAPGKGLEWVSGIYGSYYSTYYADSVKGRFTISRDNSKNTLYLQNNSLRAEDTAVYYCARHSWDYYFDYWGQGTINTVSSGGGGSGGGGSGGG (1) GSDICIMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKIMAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYHYGYGSPYTFGRGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 238] STAT1 EVQLLESGGGLVQPGGSLRLSCAASGFTESYSSMYWVRQAPGKGLEWVSSESSYGFESTYYADSVKGRFTISRDNSKNTLYLQMNSERAEDTANNYCARSWGYYHYLDYWGQGTINTVSSGGGGSGGGGSG (2) GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTWHPYPSTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHHH* [SEQ ID NO: 239] TENS4 EVQLLESGGGEVQPGGSLRLSCAASGRIFSGYSMSWVRQAPGKGLEVAISSESSGYYSTYYADSVKGRFTISRDNSKNTLYEQMNSLRAEDTAVYYCARVYINGSPWENPAMDYWEQGTENTVSSGGGGSG GGGSGGGGSDIQMTQSPSSLSASNIGDRVTITCRASCISISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWYYWNIPPTEGQGTKLEIKRLGDYKDHDGDYK DFIDIYKDDDDKAAAHFEHHHH* [SEQ ID NO: 240] TNFRS EVQLLESGGGLVQPGGSLRLSCAASGFTFYSSGMYWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYKARFIGYSYSEDYWEQGTENTVSSGGGGSGGGGSGGG F14 GSDIQMTQSPSSISASVGDRVTITCRASCISISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGVEYPHTFXQGTKLEIKRLXDYKDHDGDYKDHDiDYKD (1) DDXKAA [SEQ ID NO: 241] TNFRS EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSERAEDTAWYCARWSHYTAHWYAYFDYWGQGTINTVSSGGGGSGGG F14 GSGGGGSDEQMTQSPSSLSASVGDRVTITCRASCISISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQYEDFATYYCQQAGYHPLTEGQGTKLEIKRIADYKDHDXDYKDHDE (2) DYXXXXDXAAXHHHHHH-SPRWXXXFAL-VXLRALXXXXFXXXXXX [SEQ ID NO: 242] TNFRS EVQLLESGGGENCIPGGSLRLSCAASGFTFGSYSMSWVRQAPGKGLEWVSSESSYYGGTSYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYKARGAYLDYWGQGTINTVSSGGGGSGGGGSGGGGS F3 (1) DEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYFPFTEGQGTKLEIKRLXXYKDHDGDYKDHDIDYKDDDD KAA [SEQ ID NO: 243] TNFRS EVQLLESGGGLVQPGGSLRLSCAASGFTFGSSYMYWVRQAPGKGLEWVSSIYGSSSSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGYYWDYMDYWGQGTLVTVSSGGGGSGGGGSGG F3 (2) GGSDEQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSEQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAWDLPTEGQGTKLEIKRLXXYKDHDGDYKDHDIDXXX TMTRRP [SEQ ID NO: 244] TNFRS EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARYYWGWYMYWGQGTLVTVSSGGGGSGGGGSGGG F3 (3) GSDIQMTCQSSLSASVGDRVITTCRASQSISSYLNWYQQKPGKAPKWYAASSEQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGWWYPLTFGQGIKLEEKRLXDYKDHDGDYKDHDIXYKDDD DXAA [SEQ ID NO: 245] UBC9 EVQLLESGGGLVQPGGSLRLSCAASGETEGYGSMSWVRQAPGKGLEWVSSISYYGSSTGYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGWWLDYWGQGTEVIVSSGGGGSGGGGSGGGG (1) SDIQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGPYPPTEGQGTKLEIKKGDYKDHDGDYKDHDIDYKDDD DKAAAHHHHHH* [SEQ ID NO: 246] UBC9 EVQLLESGGGLVQPGGSLRLSCAASGETFYGSSMSWVRQAPGKGLEMSGISYSSSYTSYADSVKGRETISRDNSKNTLYLQMNSERAEDTAVYYCARATSYWFTYFGVIDYWGQGTLVTVSSGGGESGG (2) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLEIYAASSLQSGVPSRESGSGSGTDETLTISSEQPEDFATYYCQQSWSPHTEGQGTKLEIKRLGDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 247] UBC9 EVQLLESGGGLVQPGGSLRLSCAASGETESSYNVISWVRQAPGKGLEWVSSIYGSSSYTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARSASWGGYEDYWGQGTLVTVSSGGGGSGGGG (3) SGGGGSDIQMMSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSEQSGVPSRESGSGSGTDFILTISSLQPEDFATYYCQQSGVSPYTEGQGTKLEIKRLGDYKDHDGDYKDHDI DYKDDDDKAAAHHHHHH* [SEQ ID NO: 248] UBE2C EVQLLESGGGLVQPGGSLRLSCAASGETEGYYSMSVVVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGGANYGGYMDYWGQGTLVTVSSGGGGSGGG (1) GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRESGSGSGTDETLTISSLQPEDFATYYCQQSSGPHPFTEGQGTKLEIKRLGDYKDHDGDYKDHD IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 249] UBE2C EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMSWVRQAPGKGLEWVSSISGYSYGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWHHPYYFDYWGQGTLVTVSSGGGGSGGGGSG (2) GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSEQSGVPSRFSGSGSGTDETLTISSLQPEDFATYYCQQGSVLSTEGQEIKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHEEHHH* [SEQ ID NO: 250] UCHL5 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGWSLDYWGQGTLVTVSSGGGGSGGGGSGGGG SDIQMTQSRSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVHFLPTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 251] Her2/ EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRVVGGDGFYAMDYWGQGTENTVSSGGGGSGG ErbB22 GGSGGGGSDIQMTDSPSSLSASVGDRVTITCRASCIDVNTAVAWYQQKPGKAPKWYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRLGDYKDHDGDYKD (4) HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 252] EGFR QVQLKQSGPGLVQPSQSLSITCTVSGESLTNYGVHINVRQSPGKGLEWELVIWSGGNTDYNTPFTSRESINKDNSKSQVFFKMNSLCISNDTAIYYCARALTYYDYEFAYWGQGTINTVSSGGGGSGG GGSGGGGSDILLTQSPVILSVSPGERVSFSCRASQSIGTNIERNYQQRTNGSPRLHKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELKLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 253] CHP-1 EVQLLESGGGLVQPGGSLRLSCAASGETFYYYGMSWVRQAPGKGLEWVSGEGYGYGTYADSVKGRETISRDNSKNMLQMNSLRAEDTAVYYCARDSYSSPYYSLDYWGQERVIVSSGGGGSGGGGSGG (1) GGSDIQMIQSPSSISASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSEQPEDFATYYCQQSYSTPYTEGQGTKLEIKREGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 254] CHP-1 EVQLLESGGGLVQPGGSLRLSCAASGFTFYSYSMGWVRQAPGKGLEWVSSIGGSGYYTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARNYNYYYGSYEDYWGQGTLVIVSSGGGGSG (2) GGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSEQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFYPHTFGQGTKLEEKREGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 255] AGAP- EVQLLESGGGLVQPGGSLRLSCAASGFTFGSYSMHRANRQAPGKGLEMSSISSYSYSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGGAYYTNPFDYWGQGTLVTVSSGGGGSGG 2 (1) GESGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQPGFYSLPTEGQGTKLEIKRLGDYKDHDGD YKDHDIDYKDDDDKAAAHHHHHHE* [SEQ ID NO: 256] AGAP- EVQLLESGGGLVQPGGSLRLSCAASGHTSSYYMYWVRQAPGKGLEWVSGISGYSYSTGYADSVKGRETISRDNSKNTLYLQMNSERAEDIAVYYCARYGYGSSEDYWGQGTLVTVSSGGGGSGGGGS 2 (2) GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGSYDPHTGQGTKLEIKRLGDYKDHDGDYKDHD IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 257] AGAP- EVQLLESGGGLVQPGGSLRLSCAASGFTEGGYSMYVVVRQAPGKGLEWVSYESSGSSSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGGGWYDYDEFDYWGIRGTLVTVSSGGGG 2 (3) SGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRESGSGSGTDETLTISSLQPEDFATYYCQQSYSTRYIEGQGTKLEIKRLGDKDHDG DYKDHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 258] AGAP- EVQLLESGGGLVQPGGSLRLSCAASGFTESSYAMSWVRQAPGKGLEVINSAISGSGGSTYYADSNIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSDYFYYSYLDYWGQGTLVTVSSGGGG 2 (4) SGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASCISISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDETLTISSLQPEDFATYYDRQGWYYPETEGQGTKLEIKRLGDYKDH DGDYKDHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 259] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGFTFYYSSMSWVRQAPGKGLEWVSSIYGGGGSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGPGHVEDYVVGQGTINTVSSGGGGSGGGG 9 (1) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYDRQQSYYVPFTEGQGTKLEIKRLGDYKDHDGDYK DHDEDYKDDDDKAAAHHHHHH* [SEQ ID NO: 260] MAPK- EVQLLESGGGLVQPGGSLKSCAASGETESSYAMSWVRQAPGKGLEVINSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSH1NYEDYWGQGTPTRISSGGGGSGGGGS 9 (2) GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDERTISSLCIPEDFATYYCQQSYSTPYTEGQGTKLEIKRILDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHHH* [SEQ ID NO: 261] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGETEGSSGMSWVRQAPGKGEEWVSGIYGSSYGTGYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGEGYHIDYWGQGTIATIVSSGGGESGGGG 9 (3) RVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGNIPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYGSSLPTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYK SGGGGSDEQMTQSPSSLSASVGDDDDDKAAAHHHHHH* [SEQ ID NO: 262] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGEFFSGGSMSWVRQAPGKGLEWVSSISSSGSSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDIAVYYCARAYYPNEDYWGQGTLVIVSSGGGGSGGGGS 9 (4) GGGGSDIQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRESGSGSEIDETLTISSLQYEDFATYYCQQSYSTPYTEGQGTKLEIKRLGDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 263] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTAMSWVRQAPGKGLEWVSGISSYGGSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARFGHAFPAFDYWGQGTLVTVSSGGGGSGG 9 (5) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRESGSGSGTDETLTISSLQPEDFATYYCQQSYSTPYTEGQGTKLEIKREGDYKDHDGDY KDHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 264] MAPK- EVQLLESGGGLVQPGGSLRLSCAASGFTESYGSMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGHGSNIDYVVGQGTENTNISSGGGGSGGG 9 (6) GSGGGGSDIQMTQSPSSLSASVGDRVITICRASQSISSYLNWYQRKPGKAPKLLIYAASSLQSGVPSRESGSGSGTDETLTISSLQPEDFATYYCQRSYSTPYTEGQGTKLEIKRLGDYKDHDGDYK DHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 265] PAK-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFSGYSMSWVRQAPGKGLEVVVSSISSSYSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSFGFDYVVGQGTLYTVSSGGGGSGGGG (1) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRESGSGSGTDETLTESSURPEDFATYYCQQYYYGVLXTEGQGTKLEIKRLGDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 266] PAK-7 EVQLLESGGGLVQPGGSLRLSCAASGFITYYSSMSWVRQAPGKGLEMSGISGGYSSTYYADSVKGRETISRDNSKWILYLQMNSLRAEDTAVYYCARGEGVIVIDYWGQGTINTVSSGGGGSGGGGS (2) GGGGSDIQMMSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKKGDYKDHDGDYKDHDI DYKDDDDKAAAHHHHHH* [SEQ ID NO: 267] PAK-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSYIYGPYSYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYVFDYWGQGTENTVSSGGGGSGGGGSG (3) GGGSDIQMTQSPSSLSASVGDRVTITCRASCISISSYLNWYQQKPGKAPKalYAASSLCISGVPSRESGSGSGTDFILTISSLQPEDFATYYCQQSYSTPYTEGQGIKLEIKRLGDYKDHDGDYKDHD IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 268] GEM EVQLLESGGGLVQPGGSLRLSCAASGFTFYYSYMYWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRETISRDNSKNILYLQMNSLRAEDTAVYYCARFYYYGFNGSFDYWGQGTLVTVSSGGGGSGG (1) GESGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSEQSGVPSRESGSGSGTDFILTISSLQPEDFATYYCQQSYSTPYTEGQEIKLEIKRLGDYKDHDGDYK DHDEDYKDDDDKAAAHHHHHH* [SEQ ID NO: 269] GEM EVQLLESGGGLVQPGGSLRLSCAASGFTFYGSYMGWVRQAPGKGLEWVSGISSYSYSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSPFHWYFDYWGQGTLVTVSSGGGGSGGGG (2) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFRDPPHTFGQGIKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 270] GNAI- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSYISGGYGYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVVYDSSYFDYWGQGTLVTVSSGGGGSGGGG 3 (1) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRESGSGSGTDETLTISSEQPEDFATYYCQQAYYGEPSTEGQEIKLEIKREGDYKDHDGDYKDHD EDYKDDDDKAAAHHHHHH* [SEQ ID NO: 271] GNAI- EVQLLESGGGGLVQPGGSLRLSCAASGFTFSSSSMSWNIRCZAPGKGLEVIVSGISGYGGEFGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSYNYEDYWGQGTLVTVSSGGGGSGG 3 (2) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQPYGYPYTFGQGTKLEIKRLGDYKDHDGDYK DHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 272] GNAI- EVQLLESGGGLVQPGGSLRLSCAASGFTFYSSGMGWVRQAPGKGLEMSSIGSSSGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVNIWYDGGFDYWGQGTINTVSSGGGGSGGGG 3 (3) SGGGGSDIQMT0SPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLCISGVPSRFSGSGSGTDETLTISSLQPEDFATYYQRQSPMLPTFGQGTKLEIKRLGDYKDFIDGDYKDFE DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 273] GNAI- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMYWVRQAPGKGLEWVSSESSGYSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDVSHGGHSFLDYWGQGTLVTVSSGGGGSGG 3 (4) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSMSEVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQADYYPPTEGQGTKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 274] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFYSYGMGWVRQAPGKGLEWVSYEYGSYGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSYFDYWGQGTLV(VSSGGGGSGGGGSGGG K-6 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGNIPSRESGSGSGTDFTLTISSLCIPEDFATYYCQQSYSTPYITGQGTKLEIKRLGDYKDHDGDYKDHDIDY (1) KDDDDKAAAHHHHHH* [SEQ ID NO: 275] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSSMHWVRQAPGKGLEWVSSISGYGYYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSYSPSAYYFDYWGQGTLVTVSSGGGGSGG K-6 GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSMSEVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYYLPTFGQGTKLEIKRLGDYKDHDGDYKDH (2) DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 276] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFYGSSMSWVRQAPGKGLEWVSGISGYGYYTSYADSVKGRETISRDNSKNMLQMNSLRAEDTAVYYCARYSASGFYFDYWGQGTLVTVSSGGGGSGGGGSGG K-6 DGGSDIQMTQSPSSLSASVGRVTITCRASQSISSYLNWYQQKPGKAPKIIIYAASSLQSGVPSRFSGSGSGTDETLTISSEQPEDFATYYCQQSYVYPETEGQGTKLEIKRLGDYKDHDGDYKDHDIDY (3) KDDDDKAAAHHHHHH* [SEQ ID NO: 277] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYSMGWVRQAPGKGLEWVSGISSYGYYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHYTTGYYIDYWGQGTENTVSSGGGGSGGGGS K-6 GGGGSDIQMTQSPSSLSASNIGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGENVPYTEGQGTKLEIKRLGDYKDHDGDYKDHD (4) IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 278] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMYWVRQAPGKGLEWVSSISGGGYGTYYADSNIKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAYPYVGSGIDYWGQGTLVTVSSGGGGSGGG K-2 GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKELIYAASSLQSGVPSRFSGSGSGTDEMISSLQPEDFATYYCQQGYSLPTEGQGTKLEIKRLGDYKDHDGDYKDHDID (1) YKDDDDKAAAHHHHHH* [SEQ ID NO: 279] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTFYYSYMGWVRQAPGKGLEWVSSISGSSYGTSYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGTGSVIDYWGQGLVTVSSGGGGSGGGGSGGG K-2 GSDIQMTQSPSSLSASNIGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDETLTISSLQPEDFATYYQRQSYSTPYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY (2) KDDDDKAAAHHHHHH* [SEQ ID NO: 280] MAP2 EVQLLESGGGLVQPGGSLRLSCAASGFTESGYYMSWVRQAPGKGEEWNISSISSGGYGTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYGPYSLDYWGQGTEMTVSSGGGGSGGGGSG K-2 GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGAYYLFTFGQGTKLEIKRLGDYKDHDGDYKDHDID (3) YKDDDDKAAAHHFEHHH* [SEQ ID NO: 281] KRAS EVQLLESGGGLVQPGGSLRLSCAASGFTFSGSYMYWVRQAPGKGLEWVSSIGSSYGYTYYADSVKGRFTISRDNSKNMLQMNSLRAEDTAVYYCARYGYFSFDYWGQGTLVTVSSGGGGSGGGGSGGGG SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYMQDHYLSTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHH* [SEQ ID NO: 282] PTPRO EVQLLESGGGLVQPGGSLRLSCAASGFTFSYSGMGWVRQAPGKGLEWVSYISSYGYSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSVSGGVEDYWGQERVIVSSGGGGSGGGGSGG (1) GGSDIQMIQSPSSLSASVGDRVTITCRASQSIXXYLNWYQQKPGKAPKLLIYAAXSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWVHYPYTFGQGTKLEEKREGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 283] PTPRO EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWGPWYAMDYWGQGTLVIVSSGGGGSGGGGSG (2) GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQ5GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHWSTWLHTFGQGTKEIKRLGDYKDHDGDYKDHDI DYKDDDDKAAAHHHHHH* [SEQ ID NO: 284] PTPRO EVQLLESGGGLVQPGGSLRLSCAASGFTFSGSYMYWVRQAPGKGLEWVSSISSGGYSKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWDYGHSHAFDYWGQGTLVTVSSGGGGSGGGG (3) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQXSXXPSTFGQGTKLEIKRLGDYKDHDGDYKDHD DYEKDDDDKAAAHHHHHH* [SEQ ID NO: 285] PTPRO EVQLLESGGGLVQPGGSLRLSCAASGFTFSGYYXSWVRQAPGKGLEWVSSISGGSYSKSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSYYFDYWGQGTENTVSSGGGGSGGGGSGGG (4) GSDIQMTQSPSSLSASVGDRVTETCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTETISSLQPEDFATYYCQQYAAYGLITFGQGTKLEIKKGDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 286] PAR- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWNVWGHWGGPYSGVGLDYWGQGTLVTVSSGG 6B (1) GGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFATYYCQQPYYPFTEGQGTKLEIKRLGDYKDHDGD YKDHDIDYKDDDDKAAAHHHHNH* [SEQ ID NO: 287] PAR- EVQLLESGGGLVQPGGSLRLSCAASGFTFSYYYMYWVRQAPGKGLEWVSYIYSYYYGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYAYYLDYWGQGTLVTVSSGGGGSGGGGSGGG 6B (2) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHWSYGLYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 288] PRD- EVQLLESQGGGLVQPGGSLRLSCAASGFTFGSYGMSWVRQAPGKGLEWVSSIYSGYSYTYYADSVKGRTISRDNSKNITLYLQMNSLRAEDTAVYYCARHGPYRGPGSMDYWGQGTLVTVSSGGGGSGG 14 (1) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSWWLLTFGQGTKLEIKRLGDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 289] PRD- EVQLLESGGGLVQPGGSLRLSCAASGFTFYSGGNISVVVRQAPGKQLEVVVSSISGGYYYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYVYGVGIDYWQQGTLVTVSSGQGGSGGG 14 (2) GSGQGGSDIQNITQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQRGYWLFTFGQGTKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHFEHHH* [SEQ ID NO: 290] PRD- EVQLLESGGGINQPGGSLRLSCAASGFTFSGYSMYVVVRQAPGKGEEWNISSIYGYYGGTSYADSVKGRFTESRDNSKNTLYLQMNSLRAEDTAVYYCARGHPINFYMDYWGQGTINTVSSGGGGSGGG 14 (3) GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPQKAPKLLIYAASSLQSQVPSRESGSGSGTDETLTISSLQPEDFAMCQQSYWLYTFQQGTKLEIKRLGDYKDHDGDYKDHDED YKDDDDKAAAHHHHHH* [SEQ ID NO: 291] PRD- EVQLLESGGGLVQPGGSLRLSCAASGFTFSGSSMSWVRQAPGKGLEWVSSIYYSYGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARVGPWANYMDYWGQGTLVTVSSGGGGSGGGGSG 14 (4) GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSWSPHTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 292] PRD- EVQLLESGGGLVQPGGSLRLSCAASGETFSSYAMSWVRQAPGKGLEWVSGIYGYYGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSNVLDYWGQGTLVTVSSQGGGSGQGGSGG 14 (5) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSVLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYGLSTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 293] TOPBP- EVQLLESGGGEV0PGGSLRLSCAASGETESGSSIVISVVVRQAPGKGLEWVSSISSGGSSTGYADSVKGRFTISRDNSKNTLYLQNINSLRAEDTAVYYCARFSWGHWSSFEDYWGQGTUTIVSSGGG 1 (1) GSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLUYAASSLQSGVPSRFSGSGSGTDFTLTESSLQPEDFATYYCQQVYDLITFGQGTKLEIKRLGDYKDHDGD YKDHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 294] TOPBP- EVQLLESGGGLVQPGGSLRLSCAASGFTFGSSSMSWVRQAPGKGLEWVSSISYGSSSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYGFDYWGQGTLVTVSSGGGGSGGGGSGG 1 (2) GGSDIQMTQSPSSLSASVGDRVTITCRASXXLNWYQQKPGKAPKLLIYXXXXSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGXXXGXXTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 295] USP-7 EVQLLESGGGLVQPGGSLRLSCAASQFTFGSSSMYWVRQAPQKGLEWSSISYYGYSTYYADSVKGRFTISRUNSKNTLYLQMNSLRAEDTAVYYCARGSGIDYWQQGTLVTVSSGGGGSGGGGSGGGG (1) SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSVYGLYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 296] USP-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFGGSSMYWVRQAPGKQLEWVSGISYYGYSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGHSEDYWGQQTLVTVSSGGGGSGQGGSGGG (2) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQKSGYPHTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 297] USP-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFGSYSMYWVRQAPGKGLEWVSGISGYSYYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYYMDYWGQGTLVTVSSGQGGSGGGGSGGGG (3) SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWDDSPHTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 298] USP-7 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVYSYPGPSSWGYFSSIDYWGQGTLVTVSSGG (4) GGSGGGGSGGGGSDIQNITQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGYPHTFGQGTKLEIKRLGDYKDH DGDYKDHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 299] PARP- EVQLLESGGGINQPGGSLRLSCAASGFTFSGSGMGWVRQAPGKGLEWVSYEGYYSSGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHHSFGYLDYWGQGTENTVSSGGGGSGGGGSG 1 GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGVHWSLHTFGQQTKLEIKRLGDYKDHDGDYKDHDI DYKDDDDKAAAHHHHHH* [SEQ ID NO: 300] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIHFYGLDYWGQGTLVTVSSGGGGSGGGGSGG 2 (1) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKRLGDYKDHDIDYKDDDDK AAAHHHHHH* [SEQ ID NO: 301] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWNSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQNINSLRAEDTAVYYCARYVYYSYSYSFDYWGQGTLVTVSSGGGGSGG 2 (2) GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKEINAASSLQSGVPSRFSGSGSGTDFTETISSLQYEDFATYYCQQSYYLPTFGQGTKLEIKRLGDYKDHDGDYKDHD DIDYKDDDIKAAAHHHHHH* [SEQ ID NO: 302] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWSAISGSGGSTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARSFHGFDYWGQGTLVTVSSGGGGSGGGGSGGGG 2 (3) SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTESSLQPEDFATYYCQQYYSDPLIFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 303] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKQLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAHYGVIDYWGQQTLVTVSSQGGGSGQGGSGG 2 (4) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPQKAPKLUYAASSLQSGVPSRFSGSGSGfDF1LTISSLQPEDFATYYCQQYYGPFTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 304] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGPSYYYIDYWGQGILVTVSSGGGGSGGGGSG 2 (5) GGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTSSLQPEDFATYYCQQSYGPFTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 305] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSHASYFDYWGQGTLVTVSSGGGGSGGGGSGGG 2 (6) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYYLLTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 306] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSYMDYWGQGTLVTVSSGGGGSGGGGSGGGGSD 2 (7) IQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSETDFILTISSLQPEDFATYYCQQSYGPPTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDDK AAAHHHHHH* [SEQ ID NO: 307] GRIP- EVQLLESGGGLVQPGGSLRLSCAASGFIFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQNANSLRAEDTAVYYCARHSGPFFDYWGQGTLVTVSSGGGGSGGGGSGG 2 (8) GGSDIQMTQSPSSLSASVGDRSVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRESGSGSGTDFTLTISSLQPEDFATYYCQQGYSLHTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 308] MAD2L- EVQLLESGGGLVQPGGSLRLSCAASGFTFGSSYMGWVRQAPGKGLEWVSGISGGGYGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAPGGHYYGYFYFDYWGQGTLVTVSSGGGGSGG 1 (1) GGSGGGGSDIQMTQSPSSLRSASVGDRVIITCRASQSISSYLNWYQQKPGKAPKWYAASSLCISGVPSRFSGSGSGIDETLTISSLQPEDFATYYCQQXXXXAHTFGQGTKLEIKRLGDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 309] MAD2L- EVQLLESGGGLVQPGGSLRLSCAASGFTFYYSSMYWVRQAPGKGLEWVSGISSGGSGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSFSYSSYLDYWGQGTLVTVSSGGGGSGGGGS 1 (2) GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQRKPGKAHLLIYAASSLQSGVPSRESGSGSGTDETLTISSLIRPEDEATYYCQQGGXXPTGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 310] MAD2L- EVQLLESGGGLVQPGGSLRLSCAASGFTFYGSPMYWVRQAPGKGLEWVSYIGYGGYYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVYGESIDYWGQGTLVTVSSGGGGSGGGGSGG 1 (3) GGSDIQMTQSPSSLSASVGDRVTITCRASIRSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYYPLTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 311] NDC80 VQLLESGGGLVQPGGSLRLSCAASGETFGYYYMSWVRQAPGKGLEWVSGIYSGSGSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSPGYYYIDYWGQGTLVTVSSGGGGSGGGGSGGG (1) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGNIPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 312] NDC80 EVQLLESGGGLVQPGGSLRLSCAASGFTFSGSSMYWVRQAPGKGLEWVSGIGSYGGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGTAVGSYFYFDYWGQGTLVIVSSGGGGSGGG (2) GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSETDFTLTISSLQPEDFATYYCQQYYYYPHTFGQGTKLEIKRLGDYKDHDGDYKDHD IDYKDDDDKAAAHHHHHH* [SEQ ID NO: 313] NDC80 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGIGSGGYYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAYYCARFYFVASPGGNLDYWGQGTLVTVSSGGGGSGGGG (3) VGDSGGGGSDIQMTQSPSSLSARVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSSPPTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 314] Spindly EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMSWVRQAPGKGLEWVSSIDYSSYYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGSYFDYWGQGTLVTVSSGGGGSGGGGSGGGGS (1) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGSPLYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHHH* [SEQ ID NO: 315] Spindly EVQLLESGGGLVQPGGSLRLSCAASGFTEYSYYMGVVVRQAPGKGLEVVVSSISYSGSGTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARASYGTSYYYGYTIDYWGQGTLVTVSSGGGG (2) SGGGGSGGGGSD10MTIRSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ5YAGPSTFGQGTKLEIKRLGDYKDHDGD YKDHDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 316] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFSYSGMSWVRQAPGKGLEWVSSIGGSSSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSINGYYDAIDYWGQGTLNITVSSGGGGSGGG (1) GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSWWGHALYTFGQGTKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHHH* [SEQ ID NO: 317] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFSYYGMSWVRQAPGKGLEWSYISYYSGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSWSSSFDYWGQGTLYTVSSGGGGSGGGGSGGG (2) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYYGPFTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 318] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFSYSGMGWVRQAPGKGLEWVSSISYGSYGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAWYCARYYYNGYFDYWGQGTLYTVSSGGGGSGGGGSGGG (3) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGNIPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYHYHSLFTEGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 319] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSYMGWVRQAPGKGLEWVSSIYSGYYSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAWYCARWASPDNSYWYLDYWGQGTLVTVSSGGGGSGGGG (4) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSETDFTLTISSLQPEDFATYYCQQAFYPHTEGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 320] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFYSSYMGWVRQAPGKGLEWVSGIGSYGSYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNWHRWFDYWGQGTLVTVSSGGGGSGGGGSGGG (5) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYYYPYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 321] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFGGYGMYWVRQAPGKGLEWVSSIYSGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGPGWVYGHSLDYWGQGTLVIVSSGGGGSGGGG (6) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNYYGYSLFTFGQGTKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 322] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFYYSSMSVVVRQAPGKGLEWVSSIGYGSGYTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAWYCARVGASGSFDYWGQGTLVTVSSGGGGSGGGGSGG (7) GGSDIQMTQSPSSLSASVGDRVIITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFATYYCQQYHYYSLYTFGQGTKLEIKRLGDYKDHDGDYKDHDIDY KDDDDKAAAHHHHHH* [SEQ ID NO: 323] PTPRK EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSSMGWVRQAPGKGLEWVSYISGYSYYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSGTYGYYIDYWGQGTLVTVSSGGGGSGGGGS (8) GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGSYFPSTFGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 324] PTPRT EVQLLESGGGLVQPGGSLRLSCAASGFTFGGYSMSWVRQAPGKGLEMSGISYGYGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGPSYSMDYWGQGTINTVSSGGGGSGGGGSGGG (1) GSDIQMTQSPSSLSASNIGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSAYLSTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 325] PTPRT EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSGMYWVRQAPGKGLEWVSGIYSYGSVTSYADSVKGRFISRDNSKNTLYLQMNSLRAEDTAVYYCARVNYFGIDYWGQGTLTVTVSSGGGGSGGGGSGGG (2) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSCiVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSWHSPPTFCQGTKLEIKRILDYKDHDGDYKDHDIDYKDD DDKAAAHHHHHH* [SEQ ID NO: 326] PTPRT EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMSWVRQAPGKGLEWVSGIYSCGGSSTSYADSVKGRFTISRDNSKNTLYIQMNSLRAEDTAVYYCARWGSSDPPMDYWGQGILVTVSSGGGGSGGGGS (3) GGGGSDIQMTQSPSSISASVGDRVTITCRASQSISSYLNINYQQKPGKAPKWYAASSLQSGVPSRESCiSGSCiTDFTLTISSLQPEDFATYYCQQHAWSPYTFGQDQGTKLEIKRLGDYKDHDGDYKDH DIDYKDDDDKAAAHHHHHH* [SEQ ID NO: 327] PGAM- EVQLLESGGGLVQPGGSLRLSCAASGFTFYSSYMYWVRQAPGKGLEWVSGISSYGGSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYGPGSVEDYWGQGTLVIVSSGGGGSGGGGSGG 5 (1) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSIQPEDFATYYCQQVYVAYSYPYTFGQGTKIEIKRLGDYKDHDGDYKDHDI DYKDDDDKAAAHHHHHH* [SEQ ID NO: 328] PGAM- EVQLLESGGGLVQPGGSLRLSCAASGFTFSGSYMYWVRQAPGKGLEWVSGISSSGDYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGYFISFEDYWGQGTLVTVSSGGGGSGGGGSG 5 (2) GGGSDIQMIQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPICLLIYAASSLQSGVPSRFSGSGSGTDFTLIISSLQPEDFATYYCQQYYWYLKITGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 329] PGAM- EVQLLEGGGLVQPGGSLRLSCAASGFIFYSYGMSWVRQAPGKGLEWVSSISYGSYYPNADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARGYGYLDYWGQGTLVTVSSGGGGSGGGGSGGGGSD 5 (3) IQMTQSPSSLSASVGDRVTITCRASQ5ISSYLNWYQQKPGKAPKLLIAASSLQSGVPSRFSGSGSGTDFILTISSLQPEDFATYYCQQYYYYPFITFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHH* [SEQ ID NO: 330] PGAM- EVQLLESGGGINQPGGSLRLSCAASGFTFGGYSNAGWVRQAPGKGLEWVSSISSYSSYTYYADSVKGRETISRDNSKNTLYLQMNSLRAEDTAVYYCARSYSFGPWLDYWGQGTLVTVSSGGGGSGGGGS 5 (4) GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYYLETEGQGTKLEIKRLGDYKDHDGDYKDHDID YKDDDDKAAAHHHHHH* [SEQ ID NO: 331] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSYISSSGGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWAPWPYGYSMDYIWGQGTLVTVSSGGGGSGGG (1) GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATTYYCQQSSYSLSTFGQGTKLEIKRLGDYKDHDGDYKDH KDIDYDDDDKAAAHHHHHH* [SEQ ID NO: 332] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFSGGSMSWVRQAPGKGLEWVSSIGYYSGYTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGYYYFDYWGQGTLVTVSSGGGGSGGGGSGGGG (2) SDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGHGYLFTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHH* [SEQ ID NO: 333] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSYISSSSSSTSYADSVKGRMSRDNSKNTLYLQMNSLRAEDTAVYYCARYWHSHYLDYWGQGTLVTVSSGGGGSGGGGSGGGG (3) SDIQMTQSPSSLSASVGDRVMCRASQSISSYLNWYQQKPGKAPKLLIYAASSIQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYWYPYTFEQGTKLEIKRLGDYKDHDGDYKDHDIDYKDDDDK AAAHHHHHH* [SEQ ID NO: 334] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFSYSYMGWVRQAPGKGLEWVSGIYGYGYSTYADSVKGRFTISRDNSKNITLYLQMNSLRAEDTAVYYCARGVWMDYWGQGTLVTVSSGGGGSGGGGSGGGGS (4) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSIQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNHSLYTEGQGTKIEIKRLGDYKDHDGDYKDHDIDYKDDDD KAAAHHHHHH* [SEQ ID NO: 335] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFYGSYMSWVRQAPGKGLEWVSSIVSGGGYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSSRYYYMDYWGQGTLVTVSSGGGGSGGGGSGG (5) GGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSWVPHTFGQGTKLEIKRLGDYKDHDGDYKDHDIDYKD DDDKAAAHHHHHH* [SEQ ID NO: 336] PTPRJ EVQLLEGGGLVQPGGSLRLSCAASGFTFGSYSMYWVRQAPGKGLEWVSSISSSSYGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVFLDYWGQGTTLVSSGGGGSGGGGSGGGGSDI (6) QMTQSPSSLSASVGDRVTIICRASQS6SYLNWYQQKPGKAPKWYAASSLQSGVPSRFSGSGSGIDFILTISSLQPEDFATYYCQQCMSLYITGQGTKLEIKRLGDYKDFIDGDYKDHDIDYKDDDDKAAA HHHHHH* [SEQ ID NO: 337] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFSSGGMSWVRQAPGKGLEWVSSIYYSSSSTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGYGYYMDYWGQGTLVTVSSGGGGSGGGGSGGG (7) GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGSYAYLSTEGQGTKLEIKRLGDYKDHDGDYKDHDIDYK DDDDKAAAHHHHHH* [SEQ ID NO: 338] PTPRJ EVQLLESGGGLVQPGGSLRLSCAASGFTFSSGGMYWVRQAPGKGLEWVSSIYGSSSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGPYASGYYYLDYWGQGTLVTVSSGGGGSGGGG (8) SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVNYSSSYPFTFGQGTKLEIKRLGDYKDHDGDYKD HDIDYKDDDDKAAAHHHHHHH* [SEQ ID NO: 339] *The structure of the scFv antibodies is described in Soderlind et al, 2000, ‘Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries’ Nature Biotechnol, 18(8):852-6, which is incorporated herein by reference in its entirety}