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logs/di_content/di_content_20250604_140737.txt

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+<figure>
+
+IGE-ABDEG LEAD SELECTION - STRESS TEST
+
+Argenx - P1429-R01-v01 - 30 JUL 2020
+
+</figure>
+
+
+<figure>
+
+RIC
+
+biologics
+
+</figure>
+
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+<!-- PageHeader="Table of contents" -->
+
+· Project information
+
+· Scope
+
+· Test samples
+
+· Method
+
+· Results
+
+· Conclusions
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="2" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Project information
+
+
+<table>
+<tr>
+<td>· Project code:</td>
+<td>P1429</td>
+</tr>
+<tr>
+<td>· LNB number:</td>
+<td>2020.007</td>
+</tr>
+<tr>
+<td>· Project manager:</td>
+<td>Gianni Vandenborre</td>
+</tr>
+<tr>
+<td>· Report name:</td>
+<td>P1429-R01_v01</td>
+</tr>
+<tr>
+<td>· Report issue date:</td>
+<td>30-JUL-2020</td>
+</tr>
+</table>
+
+
+<figure>
+
+<!-- PageFooter="RIC" -->
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="3" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Scope
+
+· Relative quantification of the PTMs present in several mAb batches that
+were derived from a forced degradation study by reduced peptide map
+analysis to assist argenx in the selection of a lead candidate
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="4" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Test samples
+
+
+<table>
+<tr>
+<th>Test sample ID client</th>
+<th>Batch No.</th>
+<th>Volume (LL)</th>
+<th>Protein concentration</th>
+</tr>
+<tr>
+<td>18E2 HIS2 ABDEG T0</td>
+<td rowspan="2">UPX 3429</td>
+<td>60</td>
+<td>1 mg/mL</td>
+</tr>
+<tr>
+<td>18E2 HIS2 ABDEG T6w 37℃</td>
+<td>60</td>
+<td></td>
+</tr>
+<tr>
+<td>18E2VL HIS LALA ABDEG T0</td>
+<td rowspan="2">UPX 3423</td>
+<td>60</td>
+<td>1 mg/ml</td>
+</tr>
+<tr>
+<td>18E2VL HIS LALA ABDEG T6w 37℃</td>
+<td>60</td>
+<td></td>
+</tr>
+<tr>
+<td>Ligelizumab mAB37 T0</td>
+<td rowspan="2">D27/01/2020</td>
+<td>60</td>
+<td>1 mg/ml</td>
+</tr>
+<tr>
+<td>Ligelizumab mAB37 T6w 37℃</td>
+<td>60</td>
+<td></td>
+</tr>
+<tr>
+<td>OmaVH15W100b_VL3 T0</td>
+<td rowspan="2">Evitria 801689.2</td>
+<td>60</td>
+<td>1 mg/mL</td>
+</tr>
+<tr>
+<td>OmaVH15W100b_VL3 T4w 37℃</td>
+<td>60</td>
+<td></td>
+</tr>
+<tr>
+<td>OmaVH15G55H_VL3S31H T0</td>
+<td rowspan="2">Evitria 801689.1</td>
+<td>60</td>
+<td>1 mg/mL</td>
+</tr>
+<tr>
+<td>OmaVH15G55H_VL3S31H T4w 37℃</td>
+<td>60</td>
+<td></td>
+</tr>
+</table>
+
+
+· Formulation buffer: PBS + PS20 0.02%
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="5" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Method
+
+· Rebuffering using Amicon Ultra Centrifugal Filter (0.5 mL, MWCO 10 kDa)
+
+· 3x conditioning step using 500 uL 100 mM Tris pH 7.5, followed by centrifugation
+
+· 450 µL 100 mM pH 7.5 + 25 uL mAb sample (at 1 ug/uL) followed by centrifugation
+
+· 3x buffer exchange steps using 450 µL 100 mM Tris pH 7.5 followed by centrifugation
+
+· Invert spin of the membrane filter to collect 50 uL (so already 1/2 dilution)
+
+· Tryptic digestion of the mAb
+
+. 25 µg protein was used (50 uL at concentration of 0,5 µg/uL + 16.3 uL 100 mM Tris-HCI pH 7.5)
+
+· Addition of 26.3 uL Rapigest 0.2% in 100 mM Tris-HCI pH 7.5
+
+· Reduction using 2.4 uL 400 mM DTT in 100 mM Tris-HCI pH 7.5
+
+· Incubation at 60℃ for 30 min
+
+· Alkylation using 5 uL 400 mM IAA in 100 mM Tris-HCI pH 7.5
+
+· Incubation at 37°℃ for 60 min
+
+· Proteolysis using 5 uL trypsin (0.4 ug/uL, enzyme/protein: 1/12,5)
+
+· Overnight Incubation at 37℃
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="6" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Method
+
+
+## · Peptide map method
+
+· Column: AdvanceBio Peptide Map column (2.1 x 250 mm, 2.7 um particles)
+
+· Mobile phase A: 0.05% TFA in H2O (v/v) (or 0.1% FA)
+
+· Mobile phase B: 0.05% TFA in acetonitrile (v/v) (or 0.1% FA)
+
+· Flow rate: 300 uL/min
+
+· Injection volume: 15 uL
+
+· Column temperature: 60℃
+
+· Gradient:
+
+
+<table>
+<tr>
+<th>Time (min)</th>
+<th>%A</th>
+<th>%B</th>
+</tr>
+<tr>
+<td>0.0</td>
+<td>99</td>
+<td>1</td>
+</tr>
+<tr>
+<td>2.0</td>
+<td>99</td>
+<td>1</td>
+</tr>
+<tr>
+<td>35.0</td>
+<td>55</td>
+<td>45</td>
+</tr>
+<tr>
+<td>36.0</td>
+<td>10</td>
+<td>90</td>
+</tr>
+<tr>
+<td>42.0</td>
+<td>10</td>
+<td>90</td>
+</tr>
+<tr>
+<td>43.0</td>
+<td>99</td>
+<td>1</td>
+</tr>
+<tr>
+<td>56.0</td>
+<td>99</td>
+<td>1</td>
+</tr>
+<tr>
+<td>28.0</td>
+<td>99</td>
+<td>1</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="7" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results (UV 214 nm chromatograms TFA runs)
+
+
+<figure>
+
+x10 2 DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_18E2HIS2 ABDEG.d
+
+18E2HIS2 ABDEG
+
+1
+
+M
+
+0
+
+×10
+
+10 2 DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_18E2HIS2 ABDEG_T6w.d
+
+18E2HIS2 ABDEG
+T6w
+
+1
+
+0
+
+M
+
+x10 2 DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_18E2VL HIS LALA ABDEG.d
+
+18E2VL HIS LALA
+ABDEG
+
+1
+
+M
+
+0
+
+×10
+
+2 DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_18E2VL HIS LALA ABDEG_T6w.d
+
+18E2VL HIS LALA
+ABDEG
+T6w
+
+1
+
+0
+
+×10 2
+
+DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_Ligelizumab mAb 37.d
+
+Ligelizumab
+
+1
+
+0
+
+x10 2
+
+DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_Ligelizumab mAb 37_T6w.d
+
+Ligelizumab
+T6w
+
+1
+
+0
+
+8
+
+1
+
+2
+
+3
+
+4
+
+5
+
+6
+
+7
+
+8
+
+9
+
+10
+
+11
+
+12
+
+13
+
+14
+
+15
+
+16
+
+17
+
+18
+
+19
+
+20
+
+21
+
+22
+
+23
+
+24
+
+25
+
+26
+
+27
+
+28
+
+29
+
+30
+
+31
+
+32
+
+33
+
+34
+
+35
+
+Response Units vs. Acquisition Time (min)
+
+</figure>
+
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results (UV 214 nm chromatograms TFA runs)
+
+
+<figure>
+
+x10 2
+
+DAD1 - A:Sig=214.0,8.0 Ref=360.0, 100.0 P1429_19JUN2020_PM_TFA_RAT_MS_OmaVH15G55H_VL3S31H.d
+
+OmaVH15G55H_VL3S31H
+
+2.5
+
+2
+
+1.5
+
+1
+
+0.5
+
+0
+
+x10 2 DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_OmaVH15G55H_VL3S31H_T4w.d
+
+OmaVH15G55H_VL3S31H
+T4w
+
+2.5
+
+2
+
+1.5
+
+1
+
+Complete sample degradation upon storage
+
+0.5
+
+0
+
+x10 2
+
+DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_OmaVH15W100b_VL3.d
+
+OmaVH15W100b_VL3
+
+2.5
+
+2
+
+1.5
+
+1
+
+0.5
+
+0
+
+x10 2 DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P1429_19JUN2020_PM_TFA_RAT_MS_OmaVH15W100b_VL3_T4w.d
+
+OmaVH15W100b_VL3
+
+T4w
+
+2.5
+
+2
+
+1.5
+
+1
+
+Complete sample degradation upon storage
+
+0.5
+
+0
+
+9
+
+1
+
+2
+
+3
+
+4
+
+5
+
+6
+
+7
+
+8
+
+9
+
+10
+
+11
+
+12
+
+13
+
+14
+
+15
+
+16
+
+17
+
+18
+
+19
+
+20
+
+21
+
+22
+
+23
+
+24
+
+25
+
+26
+
+27
+
+28
+
+29
+
+30
+
+31
+
+32
+
+33
+
+34
+
+35
+
+Response Units vs. Acquisition Time (min)
+
+</figure>
+
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results Ligelizumab mAb 37- Identity
+
+
+<table>
+<tr>
+<th>RT</th>
+<th>Mass</th>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Tgt Seq Mass</th>
+<th>Diff (Bio, ppm)</th>
+<th>Pred Mods</th>
+</tr>
+<tr>
+<td>22.08</td>
+<td>1954.0192</td>
+<td>QVQLVQSGAEVMKPGSSVK</td>
+<td>HC(001-019)</td>
+<td>1954.0194</td>
+<td>-0.09</td>
+<td>pyroGlu</td>
+</tr>
+<tr>
+<td>5.72</td>
+<td>492.2353</td>
+<td>VSCK</td>
+<td>HC(020-023)</td>
+<td>492.2366</td>
+<td>-2.69</td>
+<td></td>
+</tr>
+<tr>
+<td>27.24</td>
+<td>1900.8885</td>
+<td>ASGYTFSWYHLEWVR</td>
+<td>HC(024-038)</td>
+<td>1900.8897</td>
+<td>-0.6</td>
+<td></td>
+</tr>
+<tr>
+<td>25.13</td>
+<td>2791.2548</td>
+<td>QAPGHGLEWMGEIDPGTFTTNYNEK</td>
+<td>HC(039-063)</td>
+<td>2791.2548</td>
+<td>-0.01</td>
+<td></td>
+</tr>
+<tr>
+<td>8.34</td>
+<td>293.1737</td>
+<td>FK</td>
+<td>HC(064-065)</td>
+<td>293.1739</td>
+<td>-0.98</td>
+<td></td>
+</tr>
+<tr>
+<td>2.01</td>
+<td>245.1483</td>
+<td>AR</td>
+<td>HC(066-067)</td>
+<td>245.1488</td>
+<td>-2.18</td>
+<td></td>
+</tr>
+<tr>
+<td>24.88</td>
+<td>2180.0311</td>
+<td>VTFTADTSTSTAYMELSSLR</td>
+<td>HC(068-087)</td>
+<td>2180.0307</td>
+<td>0.16</td>
+<td></td>
+</tr>
+<tr>
+<td>15.70</td>
+<td>1333.5591</td>
+<td>SEDTAVYYCAR</td>
+<td>HC(088-098)</td>
+<td>1333.5609</td>
+<td>-1.36</td>
+<td></td>
+</tr>
+<tr>
+<td>24.80</td>
+<td>3224.4449</td>
+<td>FSHFSGSNHDYFDYWGQGTLVTVSSASTK</td>
+<td>HC(099-127)</td>
+<td>3224.4476</td>
+<td>-0.82</td>
+<td></td>
+</tr>
+<tr>
+<td>22.47</td>
+<td>1185.6394</td>
+<td>GPSVFPLAPSSK</td>
+<td>HC(128-139)</td>
+<td>1185.6394</td>
+<td>-0.02</td>
+<td></td>
+</tr>
+<tr>
+<td>20.35</td>
+<td>1320.6699</td>
+<td>STSGGTAALGCLVK</td>
+<td>HC(140-153)</td>
+<td>1320.6708</td>
+<td>-0.63</td>
+<td></td>
+</tr>
+<tr>
+<td>31.68</td>
+<td>8014.9553</td>
+<td>STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK</td>
+<td>HC(140-216)</td>
+<td>8014.9674</td>
+<td>-1.5</td>
+<td></td>
+</tr>
+<tr>
+<td>30.99</td>
+<td>6712.3060</td>
+<td>DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK</td>
+<td>HC(154-216)</td>
+<td>6712.3072</td>
+<td>-0.18</td>
+<td></td>
+</tr>
+<tr>
+<td>3.77</td>
+<td>360.2002</td>
+<td>VDK</td>
+<td>HC(217-219)</td>
+<td>360.2009</td>
+<td>-1.87</td>
+<td></td>
+</tr>
+<tr>
+<td>3.06</td>
+<td>488.2955</td>
+<td>VDKK</td>
+<td>HC(217-220)</td>
+<td>488.2959</td>
+<td>-0.65</td>
+<td></td>
+</tr>
+<tr>
+<td>8.41</td>
+<td>599.3643</td>
+<td>KVEPK</td>
+<td>HC(220-224)</td>
+<td>599.3643</td>
+<td>-0.02</td>
+<td></td>
+</tr>
+<tr>
+<td>7.89</td>
+<td>471.2683</td>
+<td>VEPK</td>
+<td>HC(221-224)</td>
+<td>471.2693</td>
+<td>-2.08</td>
+<td></td>
+</tr>
+<tr>
+<td>2.05</td>
+<td>508.1940</td>
+<td>SCDK</td>
+<td>HC(225-228)</td>
+<td>508.1952</td>
+<td>-2.27</td>
+<td></td>
+</tr>
+<tr>
+<td>27.42</td>
+<td>3333.6280</td>
+<td>SCDKTHTCPPCPAPELLGGPSVFLFPPKPK</td>
+<td>HC(225-254)</td>
+<td>3333.6349</td>
+<td>-2.07</td>
+<td></td>
+</tr>
+<tr>
+<td>28.13</td>
+<td>2843.4478</td>
+<td>THTCPPCPAPELLGGPSVFLFPPKPK</td>
+<td>HC(229-254)</td>
+<td>2843.4503</td>
+<td>-0.87</td>
+<td></td>
+</tr>
+<tr>
+<td>17.74</td>
+<td>880.4646</td>
+<td>DTLYITR</td>
+<td>HC(255-261)</td>
+<td>880.4654</td>
+<td>-1.01</td>
+<td></td>
+</tr>
+<tr>
+<td>22.01</td>
+<td>2166.0153</td>
+<td>EPEVTCVVVDVSHEDPEVK</td>
+<td>HC(262-280)</td>
+<td>2166.0151</td>
+<td>0.1</td>
+<td></td>
+</tr>
+<tr>
+<td>22.33</td>
+<td>1676.7946</td>
+<td>FNWYVDGVEVHNAK</td>
+<td>HC(281-294)</td>
+<td>1676.7947</td>
+<td>-0.08</td>
+<td></td>
+</tr>
+<tr>
+<td>4.62</td>
+<td>500.3064</td>
+<td>TKPR</td>
+<td>HC(295-298)</td>
+<td>500.3071</td>
+<td>-1.34</td>
+<td></td>
+</tr>
+<tr>
+<td>11.17</td>
+<td>2633.0333</td>
+<td>EEQYNSTYR</td>
+<td>HC(299-307)</td>
+<td>2633.0386</td>
+<td>-2.04</td>
+<td>G0F</td>
+</tr>
+<tr>
+<td>28.69</td>
+<td>1806.9974</td>
+<td>VVSVLTVLHQDWLNGK</td>
+<td>HC(308-323)</td>
+<td>1806.9992</td>
+<td>-0.99</td>
+<td></td>
+</tr>
+<tr>
+<td>27.74</td>
+<td>2227.1996</td>
+<td>VVSVLTVLHQDWLNGKEYK</td>
+<td>HC(308-326)</td>
+<td>2227.2001</td>
+<td>-0.24</td>
+<td></td>
+</tr>
+<tr>
+<td>6.58</td>
+<td>438.2106</td>
+<td>EYK</td>
+<td>HC(324-326)</td>
+<td>438.2115</td>
+<td>-1.96</td>
+<td></td>
+</tr>
+<tr>
+<td>1.98</td>
+<td>306.1355</td>
+<td>CK</td>
+<td>HC(327-328)</td>
+<td>306.1362</td>
+<td>-2.24</td>
+<td></td>
+</tr>
+<tr>
+<td>3.17</td>
+<td>446.2480</td>
+<td>VSNK</td>
+<td>HC(329-332)</td>
+<td>446.2489</td>
+<td>-1.93</td>
+<td></td>
+</tr>
+<tr>
+<td>17.99</td>
+<td>837.4955</td>
+<td>ALPAPIEK</td>
+<td>HC(333-340)</td>
+<td>837.4960</td>
+<td>-0.59</td>
+<td></td>
+</tr>
+<tr>
+<td>8.03</td>
+<td>447.2685</td>
+<td>TISK</td>
+<td>HC(341-344)</td>
+<td>447.2693</td>
+<td>-1.69</td>
+<td></td>
+</tr>
+<tr>
+<td>6.37</td>
+<td>655.3768</td>
+<td>AKGQPR</td>
+<td>HC(345-350)</td>
+<td>655.3766</td>
+<td>0.34</td>
+<td></td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="10" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results Ligelizumab mAb 37- Identity
+
+
+<table>
+<tr>
+<th>RT</th>
+<th>Mass</th>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Tgt Seq Mass</th>
+<th>Diff (Bio, ppm)</th>
+<th>Pred Mods</th>
+</tr>
+<tr>
+<td>5.33</td>
+<td>456.2435</td>
+<td>GQPR</td>
+<td>HC(347-350)</td>
+<td>456.2445</td>
+<td>-2.18</td>
+<td></td>
+</tr>
+<tr>
+<td>18.59</td>
+<td>1285.6662</td>
+<td>EPQVYTLPPSR</td>
+<td>HC(351-361)</td>
+<td>1285.6667</td>
+<td>-0.32</td>
+<td></td>
+</tr>
+<tr>
+<td>19.68</td>
+<td>1871.9613</td>
+<td>EPQVYTLPPSRDELTK</td>
+<td>HC(351-366)</td>
+<td>1871.9629</td>
+<td>-0.85</td>
+<td></td>
+</tr>
+<tr>
+<td>10.34</td>
+<td>604.3060</td>
+<td>DELTK</td>
+<td>HC(362-366)</td>
+<td>604.3068</td>
+<td>-1.39</td>
+<td></td>
+</tr>
+<tr>
+<td>21.70</td>
+<td>1160.6224</td>
+<td>NQVSLTCLVK</td>
+<td>HC(367-376)</td>
+<td>1160.6224</td>
+<td>0</td>
+<td></td>
+</tr>
+<tr>
+<td>24.21</td>
+<td>2543.1234</td>
+<td>GFYPSDIAVEWESNGQPENNYK</td>
+<td>HC(377-398)</td>
+<td>2543.1241</td>
+<td>-0.27</td>
+<td></td>
+</tr>
+<tr>
+<td>25.93</td>
+<td>1872.9143</td>
+<td>TTPPVLDSDGSFFLYSK</td>
+<td>HC(399-415)</td>
+<td>1872.9146</td>
+<td>-0.14</td>
+<td></td>
+</tr>
+<tr>
+<td>12.40</td>
+<td>574.3323</td>
+<td>LTVDK</td>
+<td>HC(416-420)</td>
+<td>574.3326</td>
+<td>-0.6</td>
+<td></td>
+</tr>
+<tr>
+<td>23.22</td>
+<td>2019.9295</td>
+<td>WQQGNVFSCSVMHEALK</td>
+<td>HC(423-439)</td>
+<td>2019.9295</td>
+<td>0.02</td>
+<td></td>
+</tr>
+<tr>
+<td>12.49</td>
+<td>822.4022</td>
+<td>FHYTQK</td>
+<td>HC(440-445)</td>
+<td>822.4024</td>
+<td>-0.26</td>
+<td></td>
+</tr>
+<tr>
+<td>18.19</td>
+<td>659.3484</td>
+<td>SLSLSPG</td>
+<td>HC(446-452)</td>
+<td>659.3490</td>
+<td>-0.99</td>
+<td></td>
+</tr>
+<tr>
+<td>16.86</td>
+<td>787.4437</td>
+<td>SLSLSPGK</td>
+<td>HC(446-453)</td>
+<td>787.4440</td>
+<td>-0.36</td>
+<td></td>
+</tr>
+<tr>
+<td>21.23</td>
+<td>1900.9548</td>
+<td>EIVMTQSPATLSVSPGER</td>
+<td>LC(001-018)</td>
+<td>1900.9564</td>
+<td>-0.87</td>
+<td></td>
+</tr>
+<tr>
+<td>11.12</td>
+<td>706.3424</td>
+<td>ATLSCR</td>
+<td>LC(019-024)</td>
+<td>706.3432</td>
+<td>-1.12</td>
+<td></td>
+</tr>
+<tr>
+<td>19.07</td>
+<td>2366.1878</td>
+<td>ASQSIGTNIHWYQQKPGQAPR</td>
+<td>LC(025-045)</td>
+<td>2366.1880</td>
+<td>-0.08</td>
+<td></td>
+</tr>
+<tr>
+<td>25.77</td>
+<td>1751.9464</td>
+<td>LLIYYASESISGIPAR</td>
+<td>LC(046-061)</td>
+<td>1751.9458</td>
+<td>0.34</td>
+<td></td>
+</tr>
+<tr>
+<td>30.53</td>
+<td>4601.0567</td>
+<td>FSGSGSGTEFTLTISSLQSEDFAVYYCQQSWSWPTTFGGGTK</td>
+<td>LC(062-103)</td>
+<td>4601.0646</td>
+<td>-1.72</td>
+<td></td>
+</tr>
+<tr>
+<td>12.43</td>
+<td>487.3001</td>
+<td>VEIK</td>
+<td>LC(104-107)</td>
+<td>487.3006</td>
+<td>-1.08</td>
+<td></td>
+</tr>
+<tr>
+<td>11.85</td>
+<td>643.4010</td>
+<td>VEIKR</td>
+<td>LC(104-108)</td>
+<td>643.4017</td>
+<td>-1.04</td>
+<td></td>
+</tr>
+<tr>
+<td>26.29</td>
+<td>2101.1184</td>
+<td>RTVAAPSVFIFPPSDEQLK</td>
+<td>LC(108-126)</td>
+<td>2101.1208</td>
+<td>-1.16</td>
+<td></td>
+</tr>
+<tr>
+<td>27.42</td>
+<td>1945.0183</td>
+<td>TVAAPSVFIFPPSDEQLK</td>
+<td>LC(109-126)</td>
+<td>1945.0197</td>
+<td>-0.71</td>
+<td></td>
+</tr>
+<tr>
+<td>33.07</td>
+<td>3723.8910</td>
+<td>TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR</td>
+<td>LC(109-142)</td>
+<td>3723.8971</td>
+<td>-1.64</td>
+<td></td>
+</tr>
+<tr>
+<td>28.60</td>
+<td>1796.8863</td>
+<td>SGTASVVCLLNNFYPR</td>
+<td>LC(127-142)</td>
+<td>1796.8880</td>
+<td>-0.92</td>
+<td></td>
+</tr>
+<tr>
+<td>1.98</td>
+<td>346.1845</td>
+<td>EAK</td>
+<td>LC(143-145)</td>
+<td>346.1852</td>
+<td>-2.12</td>
+<td></td>
+</tr>
+<tr>
+<td>14.20</td>
+<td>559.3115</td>
+<td>VQWK</td>
+<td>LC(146-149)</td>
+<td>559.3118</td>
+<td>-0.58</td>
+<td></td>
+</tr>
+<tr>
+<td>13.95</td>
+<td>2134.9593</td>
+<td>VDNALQSGNSQESVTEQDSK</td>
+<td>LC(150-169)</td>
+<td>2134.9615</td>
+<td>-1.01</td>
+<td></td>
+</tr>
+<tr>
+<td>21.54</td>
+<td>3618.6975</td>
+<td>VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK</td>
+<td>LC(150-183)</td>
+<td>3618.7021</td>
+<td>-1.26</td>
+<td></td>
+</tr>
+<tr>
+<td>21.61</td>
+<td>1501.7507</td>
+<td>DSTYSLSSTLTLSK</td>
+<td>LC(170-183)</td>
+<td>1501.7512</td>
+<td>-0.34</td>
+<td></td>
+</tr>
+<tr>
+<td>8.49</td>
+<td>624.2752</td>
+<td>ADYEK</td>
+<td>LC(184-188)</td>
+<td>624.2755</td>
+<td>-0.47</td>
+<td></td>
+</tr>
+<tr>
+<td>17.03</td>
+<td>2140.0696</td>
+<td>HKVYACEVTHQGLSSPVTK</td>
+<td>LC(189-207)</td>
+<td>2140.0735</td>
+<td>-1.84</td>
+<td></td>
+</tr>
+<tr>
+<td>17.75</td>
+<td>1874.9187</td>
+<td>VYACEVTHQGLSSPVTK</td>
+<td>LC(191-207)</td>
+<td>1874.9197</td>
+<td>-0.5</td>
+<td></td>
+</tr>
+<tr>
+<td>10.15</td>
+<td>522.2544</td>
+<td>SFNR</td>
+<td>LC(208-211)</td>
+<td>522.2551</td>
+<td>-1.22</td>
+<td></td>
+</tr>
+<tr>
+<td>2.06</td>
+<td>364.1044</td>
+<td>GEC</td>
+<td>LC(212-214)</td>
+<td>364.1053</td>
+<td>-2.35</td>
+<td></td>
+</tr>
+</table>
+
+
+<figure>
+</figure>
+
+
+RIC
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="11" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results Ligelizumab mAb 37- Identity
+
+\>HEAVY CHAIN: Ligelizumab mAb 37
+
+QVQLVQSGAEVMKPGSSVKVSCKASGYTFSWYHLEWVRQAPGHGLEWMGEIDPGTFTTNYNEKFKARVTFTADTSTSTAYMELSSLR
+SEDTAVYYCARFSHESGSNHDYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH
+TFPAVLOSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITR
+EPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
+PREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH
+EALKFHYTOKSLSLSPGK
+
+\>LIGHT CHAIN: Ligelizumab mAb 37
+
+EIVMTQSPATLSVSPGERATLSCRASOSIGTNIHWYQQKPGQAPRLLIYYASESISGIPARFSGSGSGTEFTLTISSLOSEDFAVYY
+COOSWSWPTTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
+LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
+
+Sequence coverage of 99.7%
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="12" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results Ligelizumab mAb 37- Modifications (oxidation)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>Ligelizumab</th>
+<th>Ligelizumab T6w</th>
+</tr>
+<tr>
+<td rowspan="2">pyroQVQLVQSGAEVMKPGSSVK</td>
+<td rowspan="2">HC(1-19)</td>
+<td rowspan="2">Oxidation</td>
+<td rowspan="2">1.6 98.4</td>
+<td>20.3</td>
+</tr>
+<tr>
+<td>79.7</td>
+</tr>
+<tr>
+<td rowspan="2">ASGYTFSWYHLEWVR</td>
+<td rowspan="2">HC(24-38)</td>
+<td rowspan="2">Oxidation</td>
+<td rowspan="2">1.5 98.5</td>
+<td>5.5</td>
+</tr>
+<tr>
+<td>94.5</td>
+</tr>
+<tr>
+<td rowspan="2">QAPGHGLEWMGEIDPGTFTTNYNEK</td>
+<td rowspan="2">HC(36-63)</td>
+<td rowspan="2">Oxidation</td>
+<td>0.8</td>
+<td>0.7</td>
+</tr>
+<tr>
+<td>99.2</td>
+<td>99.3</td>
+</tr>
+<tr>
+<td>VTFTADTSTSTAYMELSSLR</td>
+<td>HC(68-87)</td>
+<td>Oxidation</td>
+<td>0.9 99.1</td>
+<td>1.2 98.8</td>
+</tr>
+<tr>
+<td>FSHFSGSNHDYFDYWGQGTLVTVSSASTK</td>
+<td>HC(99-127)</td>
+<td>Oxidation</td>
+<td>0.5 99.5</td>
+<td>0.7 99.3</td>
+</tr>
+<tr>
+<td>WQQGNVFSCSVMHEALK</td>
+<td>HC(423-439)</td>
+<td>Oxidation</td>
+<td>2.3 97.7</td>
+<td>10.6 89.4</td>
+</tr>
+<tr>
+<td>EIVMTQSPATLSVSPGER</td>
+<td>LC(1-18)</td>
+<td>Oxidation</td>
+<td>1.8 98.2</td>
+<td>2.2 97.8</td>
+</tr>
+</table>
+
+BOLD: relevant increase upon stressing
+
+Note: Only modifications > 0.5% are reported
+
+
+<figure>
+</figure>
+
+
+RIC
+biologics
+
+<!-- PageNumber="13" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results Ligelizumab mAb 37- Modifications (deam/isoD)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>Ligelizumab</th>
+<th>Ligelizumab T6w</th>
+</tr>
+<tr>
+<td rowspan="2">FNWYVDGVEVHNAK</td>
+<td rowspan="2">HC(281-294)</td>
+<td>IsoD</td>
+<td>0.7</td>
+<td>1.6</td>
+</tr>
+<tr>
+<td></td>
+<td>99.3</td>
+<td>98.4</td>
+</tr>
+<tr>
+<td rowspan="3">VVSVLTVLHQDWLNGK</td>
+<td rowspan="3">HC(308-323)</td>
+<td>Deam</td>
+<td>1.0</td>
+<td>1.4</td>
+</tr>
+<tr>
+<td></td>
+<td>97.4</td>
+<td>96.1</td>
+</tr>
+<tr>
+<td>Succ</td>
+<td>1.6</td>
+<td>2.5</td>
+</tr>
+<tr>
+<td rowspan="2">NQVSLTCLVK</td>
+<td rowspan="2">HC(367-376)</td>
+<td>Deam</td>
+<td>2.5</td>
+<td>3.5</td>
+</tr>
+<tr>
+<td></td>
+<td>97.5</td>
+<td>96.5</td>
+</tr>
+<tr>
+<td rowspan="2">GFYPSDIAVEWESNGQPENNYK</td>
+<td rowspan="2">HC(377-398)</td>
+<td>Deam</td>
+<td>4.4</td>
+<td>24.6</td>
+</tr>
+<tr>
+<td></td>
+<td>95.6</td>
+<td>75.4</td>
+</tr>
+<tr>
+<td>TVAAPSVFIFPPSDEQLK</td>
+<td>LC(109-126)</td>
+<td>IsoD</td>
+<td>0.0 100.0</td>
+<td>0.9 99.1</td>
+</tr>
+<tr>
+<td></td>
+<td rowspan="2">LC(127-142)</td>
+<td>Deam</td>
+<td>0.9</td>
+<td>0.8</td>
+</tr>
+<tr>
+<td>SGTASVVCLLNNFYPR</td>
+<td></td>
+<td>99.1</td>
+<td>99.2</td>
+</tr>
+<tr>
+<td>VDNALQSGNSQESVTEQDSK</td>
+<td>LC(150-169)</td>
+<td>IsoD</td>
+<td>0.5 99.5</td>
+<td>1.0 99.0</td>
+</tr>
+</table>
+
+BOLD: relevant increase upon stressing
+
+Note: Only modifications > 0.5% are reported
+
+
+<figure>
+</figure>
+
+
+RIC
+biologics
+
+<!-- PageNumber="14" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Results Ligelizumab mAb 37 - Modifications (pyroE)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>Ligelizumab</th>
+<th>Ligelizumab T6w</th>
+</tr>
+<tr>
+<td>QVQLVQSGAEVMKPGSSVK</td>
+<td>HC(1-19)</td>
+<td>PyroE</td>
+<td>100.0 0.0</td>
+<td>100.0 0.0</td>
+</tr>
+<tr>
+<td>EIVMTQSPATLSVSPGER</td>
+<td>LC(1-18)</td>
+<td>PyroE</td>
+<td>1.1 98.9</td>
+<td>2.0 98.0</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="15" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results Ligelizumab mAB 37- Modifications
+
+\>HEAVY CHAIN: Ligelizumab
+
+QVQLVQSGAEVMKPGSSVKVSCKASGYTFSWYHLEWVRQAPGHGLEWMGEIDPGTFTTNYNEKFKARVTFTADTSTSTAYMELSSL
+RSEDTAVYYCARFSHFSGSNHDYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
+HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYIT
+REPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
+QPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV
+MHEALKFHYTOKSLSLSPGK
+
+\>LIGHT CHAIN: Ligelizumab
+
+EIVMTQSPATLSVSPGERATLSCRASOSIGTNIHWYQQKPGQAPRLLIYYASESISGIPARFSGSGSGTEFTLTISSLOSEDFAVYY
+COOSWSWPTTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS
+LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+
+RED: relevant increase upon stressing
+
+<!-- PageNumber="16" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2 HIS2 ABDEG - Identity
+
+
+<table>
+<tr>
+<th>RT</th>
+<th>Mass</th>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Tgt Seq Mass</th>
+<th>Diff (Bio, ppm)</th>
+<th>Pred Mods</th>
+</tr>
+<tr>
+<td>23.52</td>
+<td>1895.0106</td>
+<td>EVQLLESGGGLVQPGGSLR</td>
+<td>HC(001-019)</td>
+<td>1895.0113</td>
+<td>-0.33</td>
+<td></td>
+</tr>
+<tr>
+<td>29.08</td>
+<td>2205.0150</td>
+<td>LSCAASGFTFSSYVMHWVR</td>
+<td>HC(020-038)</td>
+<td>2205.0136</td>
+<td>0.67</td>
+<td></td>
+</tr>
+<tr>
+<td>31.91</td>
+<td>5241.4455</td>
+<td>LSCAASGFTFSSYVMHWVRQAPGKGLEWVSSIYHDGSHTYYADFVK</td>
+<td>HC(020-065)</td>
+<td>5241.4542</td>
+<td>-1.66</td>
+<td></td>
+</tr>
+<tr>
+<td>6.07</td>
+<td>499.2752</td>
+<td>QAPGK</td>
+<td>HC(039-043)</td>
+<td>499.2755</td>
+<td>-0.47</td>
+<td></td>
+</tr>
+<tr>
+<td>25.58</td>
+<td>2573.1878</td>
+<td>GLEWVSSIYHDGSHTYYADFVK</td>
+<td>HC(044-065)</td>
+<td>2573.1863</td>
+<td>0.56</td>
+<td></td>
+</tr>
+<tr>
+<td>15.94</td>
+<td>835.4666</td>
+<td>GRFTISR</td>
+<td>HC(066-072)</td>
+<td>835.4664</td>
+<td>0.2</td>
+<td></td>
+</tr>
+<tr>
+<td>16.06</td>
+<td>622.3440</td>
+<td>FTISR</td>
+<td>HC(068-072)</td>
+<td>622.3439</td>
+<td>0.21</td>
+<td></td>
+</tr>
+<tr>
+<td>2.31</td>
+<td>462.2077</td>
+<td>DNSK</td>
+<td>HC(073-076)</td>
+<td>462.2074</td>
+<td>0.47</td>
+<td></td>
+</tr>
+<tr>
+<td>22.53</td>
+<td>1351.6908</td>
+<td>NTLYLQMNSLR</td>
+<td>HC(077-087)</td>
+<td>1351.6918</td>
+<td>-0.78</td>
+<td></td>
+</tr>
+<tr>
+<td>15.52</td>
+<td>1289.5593</td>
+<td>AEDTAVYYCAK</td>
+<td>HC(088-098)</td>
+<td>1289.5598</td>
+<td>-0.41</td>
+<td></td>
+</tr>
+<tr>
+<td>28.16</td>
+<td>3400.5399</td>
+<td>GTSYSGSYYYTDPFFGSWGQGTLVTVSSASTK</td>
+<td>HC(099-130)</td>
+<td>3400.5412</td>
+<td>-0.39</td>
+<td></td>
+</tr>
+<tr>
+<td>22.49</td>
+<td>1185.6381</td>
+<td>GPSVFPLAPSSK</td>
+<td>HC(131-142)</td>
+<td>1185.6394</td>
+<td>-1.08</td>
+<td></td>
+</tr>
+<tr>
+<td>20.36</td>
+<td>1320.6693</td>
+<td>STSGGTAALGCLVK</td>
+<td>HC(143-156)</td>
+<td>1320.6708</td>
+<td>-1.13</td>
+<td></td>
+</tr>
+<tr>
+<td>31.67</td>
+<td>8014.9598</td>
+<td>STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK</td>
+<td>HC(143-219)</td>
+<td>8014.9674</td>
+<td>-0.95</td>
+<td></td>
+</tr>
+<tr>
+<td>30.97</td>
+<td>6712.2931</td>
+<td>DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK</td>
+<td>HC(157-219)</td>
+<td>6712.3072</td>
+<td>-2.1</td>
+<td></td>
+</tr>
+<tr>
+<td>3.07</td>
+<td>488.2955</td>
+<td>VDKK</td>
+<td>HC(220-223)</td>
+<td>488.2959</td>
+<td>-0.72</td>
+<td></td>
+</tr>
+<tr>
+<td>8.41</td>
+<td>599.3646</td>
+<td>KVEPK</td>
+<td>HC(223-227)</td>
+<td>599.3643</td>
+<td>0.52</td>
+<td></td>
+</tr>
+<tr>
+<td>7.89</td>
+<td>471.2689</td>
+<td>VEPK</td>
+<td>HC(224-227)</td>
+<td>471.2693</td>
+<td>-0.94</td>
+<td></td>
+</tr>
+<tr>
+<td>2.06</td>
+<td>508.1946</td>
+<td>SCDK</td>
+<td>HC(228-231)</td>
+<td>508.1952</td>
+<td>-1.19</td>
+<td></td>
+</tr>
+<tr>
+<td>27.38</td>
+<td>3333.6341</td>
+<td>SCDKTHTCPPCPAPELLGGPSVFLFPPKPK</td>
+<td>HC(228-257)</td>
+<td>3333.6349</td>
+<td>-0.22</td>
+<td></td>
+</tr>
+<tr>
+<td>28.10</td>
+<td>2843.4509</td>
+<td>THTCPPCPAPELLGGPSVFLFPPKPK</td>
+<td>HC(232-257)</td>
+<td>2843.4503</td>
+<td>0.21</td>
+<td></td>
+</tr>
+<tr>
+<td>17.76</td>
+<td>880.4659</td>
+<td>DTLYITR</td>
+<td>HC(258-264)</td>
+<td>880.4654</td>
+<td>0.54</td>
+<td></td>
+</tr>
+<tr>
+<td>22.02</td>
+<td>2166.0145</td>
+<td>EPEVTCVVVDVSHEDPEVK</td>
+<td>HC(265-283)</td>
+<td>2166.0151</td>
+<td>-0.25</td>
+<td></td>
+</tr>
+<tr>
+<td>22.34</td>
+<td>1676.7950</td>
+<td>FNWYVDGVEVHNAK</td>
+<td>HC(284-297)</td>
+<td>1676.7947</td>
+<td>0.16</td>
+<td></td>
+</tr>
+<tr>
+<td>4.63</td>
+<td>500.3070</td>
+<td>TKPR</td>
+<td>HC(298-301)</td>
+<td>500.3071</td>
+<td>-0.23</td>
+<td></td>
+</tr>
+<tr>
+<td>11.96</td>
+<td>1188.5050</td>
+<td>EEQYNSTYR</td>
+<td>HC(302-310)</td>
+<td>1188.5047</td>
+<td>0.24</td>
+<td></td>
+</tr>
+<tr>
+<td>11.18</td>
+<td>2633.0396</td>
+<td>EEQYNSTYR</td>
+<td>HC(302-310)</td>
+<td>2633.0386</td>
+<td>0.38</td>
+<td>G0F</td>
+</tr>
+<tr>
+<td>28.68</td>
+<td>1806.9994</td>
+<td>VVSVLTVLHQDWLNGK</td>
+<td>HC(311-326)</td>
+<td>1806.9992</td>
+<td>0.08</td>
+<td></td>
+</tr>
+<tr>
+<td>27.71</td>
+<td>2227.2001</td>
+<td>VVSVLTVLHQDWLNGKEYK</td>
+<td>HC(311-329)</td>
+<td>2227.2001</td>
+<td>0.01</td>
+<td></td>
+</tr>
+<tr>
+<td>6.58</td>
+<td>438.2110</td>
+<td>EYK</td>
+<td>HC(327-329)</td>
+<td>438.2115</td>
+<td>-0.95</td>
+<td></td>
+</tr>
+<tr>
+<td>1.97</td>
+<td>306.1361</td>
+<td>CK</td>
+<td>HC(330-331)</td>
+<td>306.1362</td>
+<td>-0.37</td>
+<td></td>
+</tr>
+<tr>
+<td>3.05</td>
+<td>446.2485</td>
+<td>VSNK</td>
+<td>HC(332-335)</td>
+<td>446.2489</td>
+<td>-0.91</td>
+<td></td>
+</tr>
+<tr>
+<td>18.00</td>
+<td>837.4964</td>
+<td>ALPAPIEK</td>
+<td>HC(336-343)</td>
+<td>837.4960</td>
+<td>0.51</td>
+<td></td>
+</tr>
+</table>
+
+
+<figure>
+</figure>
+
+
+RIC
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="17" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+### Results 18E2 HIS2 ABDEG - Identity
+
+
+<table>
+<tr>
+<th>RT</th>
+<th>Mass</th>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Tgt Seq Mass</th>
+<th>Diff (Bio, ppm)</th>
+<th>Pred Mods</th>
+</tr>
+<tr>
+<td>8.04</td>
+<td>447.2689</td>
+<td>TISK</td>
+<td>HC(344-347)</td>
+<td>447.2693</td>
+<td>-0.89</td>
+<td></td>
+</tr>
+<tr>
+<td>6.37</td>
+<td>655.3762</td>
+<td>AKGQPR</td>
+<td>HC(348-353)</td>
+<td>655.3766</td>
+<td>-0.53</td>
+<td></td>
+</tr>
+<tr>
+<td>5.34</td>
+<td>456.2436</td>
+<td>GQPR</td>
+<td>HC(350-353)</td>
+<td>456.2445</td>
+<td>-2</td>
+<td></td>
+</tr>
+<tr>
+<td>18.62</td>
+<td>1285.6659</td>
+<td>EPQVYTLPPSR</td>
+<td>HC(354-364)</td>
+<td>1285.6667</td>
+<td>-0.59</td>
+<td></td>
+</tr>
+<tr>
+<td>19.70</td>
+<td>1871.9625</td>
+<td>EPQVYTLPPSRDELTK</td>
+<td>HC(354-369)</td>
+<td>1871.9629</td>
+<td>-0.2</td>
+<td></td>
+</tr>
+<tr>
+<td>10.35</td>
+<td>604.3067</td>
+<td>DELTK</td>
+<td>HC(365-369)</td>
+<td>604.3068</td>
+<td>-0.24</td>
+<td></td>
+</tr>
+<tr>
+<td>21.71</td>
+<td>1160.6228</td>
+<td>NQVSLTCLVK</td>
+<td>HC(370-379)</td>
+<td>1160.6224</td>
+<td>0.4</td>
+<td></td>
+</tr>
+<tr>
+<td>24.22</td>
+<td>2543.1244</td>
+<td>GFYPSDIAVEWESNGQPENNYK</td>
+<td>HC(380-401)</td>
+<td>2543.1241</td>
+<td>0.12</td>
+<td></td>
+</tr>
+<tr>
+<td>25.93</td>
+<td>1872.9139</td>
+<td>TTPPVLDSDGSFFLYSK</td>
+<td>HC(402-418)</td>
+<td>1872.9146</td>
+<td>-0.35</td>
+<td></td>
+</tr>
+<tr>
+<td>12.41</td>
+<td>574.3327</td>
+<td>LTVDK</td>
+<td>HC(419-423)</td>
+<td>574.3326</td>
+<td>0.12</td>
+<td></td>
+</tr>
+<tr>
+<td>1.97</td>
+<td>261.1431</td>
+<td>SR</td>
+<td>HC(424-425)</td>
+<td>261.1437</td>
+<td>-2.18</td>
+<td></td>
+</tr>
+<tr>
+<td>33.08</td>
+<td>2263.0592</td>
+<td>SRWQQGNVFSCSVMHEALK</td>
+<td>HC(424-442)</td>
+<td>2263.0627</td>
+<td>-1.54</td>
+<td></td>
+</tr>
+<tr>
+<td>23.63</td>
+<td>3067.4465</td>
+<td>SRWQQGNVFSCSVMHEALKFHYTQK</td>
+<td>HC(424-448)</td>
+<td>3067.4545</td>
+<td>-2.63</td>
+<td></td>
+</tr>
+<tr>
+<td>23.22</td>
+<td>2019.9271</td>
+<td>WQQGNVFSCSVMHEALK</td>
+<td>HC(426-442)</td>
+<td>2019.9295</td>
+<td>-1.18</td>
+<td></td>
+</tr>
+<tr>
+<td>12.52</td>
+<td>822.4028</td>
+<td>FHYTQK</td>
+<td>HC(443-448)</td>
+<td>822.4024</td>
+<td>0.43</td>
+<td></td>
+</tr>
+<tr>
+<td>18.20</td>
+<td>659.3486</td>
+<td>SLSLSPG</td>
+<td>HC(449-455)</td>
+<td>659.3490</td>
+<td>-0.58</td>
+<td></td>
+</tr>
+<tr>
+<td>22.64</td>
+<td>1957.0099</td>
+<td>SSELTQDPAVSVALGQTVR</td>
+<td>LC(001-019)</td>
+<td>1957.0116</td>
+<td>-0.91</td>
+<td></td>
+</tr>
+<tr>
+<td>8.99</td>
+<td>848.3799</td>
+<td>ITCQGDR</td>
+<td>LC(020-026)</td>
+<td>848.3811</td>
+<td>-1.4</td>
+<td></td>
+</tr>
+<tr>
+<td>8.03</td>
+<td>431.2486</td>
+<td>LGSR</td>
+<td>LC(027-030)</td>
+<td>431.2492</td>
+<td>-1.39</td>
+<td></td>
+</tr>
+<tr>
+<td>24.57</td>
+<td>2703.3443</td>
+<td>YIHWYQQKPGQAPVLVIYDDDR</td>
+<td>LC(031-052)</td>
+<td>2703.3445</td>
+<td>-0.08</td>
+<td></td>
+</tr>
+<tr>
+<td>23.74</td>
+<td>3581.8172</td>
+<td>YIHWYQQKPGQAPVLVIYDDDRRPSGIPDR</td>
+<td>LC(031-060)</td>
+<td>3581.8168</td>
+<td>0.13</td>
+<td></td>
+</tr>
+<tr>
+<td>13.04</td>
+<td>896.4826</td>
+<td>RPSGIPDR</td>
+<td>LC(053-060)</td>
+<td>896.4828</td>
+<td>-0.25</td>
+<td></td>
+</tr>
+<tr>
+<td>25.10</td>
+<td>5127.3123</td>
+<td>FSGSSSGNTASLTITGAQAEDEADYYCQSADSSGNPVFGGGTQLTVLGQPK</td>
+<td>LC(061-111)</td>
+<td>5127.3164</td>
+<td>-0.8</td>
+<td></td>
+</tr>
+<tr>
+<td>23.58</td>
+<td>1985.0103</td>
+<td>AAPSVTLFPPSSEELQANK</td>
+<td>LC(112-130)</td>
+<td>1985.0106</td>
+<td>-0.13</td>
+<td></td>
+</tr>
+<tr>
+<td>34.71</td>
+<td>4177.1390</td>
+<td>AAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWK</td>
+<td>LC(112-150)</td>
+<td>4177.1446</td>
+<td>-1.33</td>
+<td></td>
+</tr>
+<tr>
+<td>33.08</td>
+<td>2210.1419</td>
+<td>ATLVCLISDFYPGAVTVAWK</td>
+<td>LC(131-150)</td>
+<td>2210.1446</td>
+<td>-1.2</td>
+<td></td>
+</tr>
+<tr>
+<td>10.21</td>
+<td>702.3549</td>
+<td>ADSSPVK</td>
+<td>LC(151-157)</td>
+<td>702.3548</td>
+<td>0.14</td>
+<td></td>
+</tr>
+<tr>
+<td>11.55</td>
+<td>989.5031</td>
+<td>AGVETTTPSK</td>
+<td>LC(158-167)</td>
+<td>989.5029</td>
+<td>0.15</td>
+<td></td>
+</tr>
+<tr>
+<td>1.96</td>
+<td>589.2819</td>
+<td>QSNNK</td>
+<td>LC(168-172)</td>
+<td>589.2820</td>
+<td>-0.15</td>
+<td></td>
+</tr>
+<tr>
+<td>24.34</td>
+<td>1742.8513</td>
+<td>YAASSYLSLTPEQWK</td>
+<td>LC(173-187)</td>
+<td>1742.8516</td>
+<td>-0.14</td>
+<td></td>
+</tr>
+<tr>
+<td>2.10</td>
+<td>398.2021</td>
+<td>SHR</td>
+<td>LC(188-190)</td>
+<td>398.2026</td>
+<td>-1.29</td>
+<td></td>
+</tr>
+<tr>
+<td>13.38</td>
+<td>1710.7519</td>
+<td>SYSCQVTHEGSTVEK</td>
+<td>LC(191-205)</td>
+<td>1710.7519</td>
+<td>-0.03</td>
+<td></td>
+</tr>
+<tr>
+<td>11.73</td>
+<td>863.3695</td>
+<td>TVAPTECS</td>
+<td>LC(206-213)</td>
+<td>863.3695</td>
+<td>0.06</td>
+<td></td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+<!-- PageFooter="biologics" -->
+
+</figure>
+
+
+<!-- PageNumber="18" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2 HIS2 ABDEG - Identity
+
+
+### >HEAVY CHAIN: 18E2HIS2
+
+EVOLLESGGGLVQPGGSLRLSCAASGFTFSSYVMHWVRQAPGKGLEWVSSIYHDGSHTYYADFVKGRFTISRDNSKNTLYLQ
+MNSLRAEDTAVYYCAKGTSYSGSYYYTDPFFGSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
+VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
+PSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
+KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
+GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYTOKSLSLSPGK
+
+
+### >LIGHT CHAIN : 18E2HIS2
+
+SSELTQDPAVSVALGQTVRITCQGDRLGSRYIHWYQQKPGQAPVLVIYDDDRRPSGIPDRFSGSSSGNTASLTITGAQAEDE
+ADYYCOSADSSGNPVFGGGTQLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTT
+PSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
+
+Sequence coverage of 99.8%
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="19" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2 HIS2 ABDEG - Modifications (oxidation)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>18E2 HIS2 ABDEG</th>
+<th>18E2 HIS2 ABDEG T6w</th>
+</tr>
+<tr>
+<td rowspan="2">WQQGNVFSCSVMHEALK</td>
+<td rowspan="2">HC(426-442)</td>
+<td rowspan="2">Oxidation</td>
+<td>3.7</td>
+<td rowspan="2">18.2 81.8</td>
+</tr>
+<tr>
+<td>96.3</td>
+</tr>
+</table>
+
+BOLD: relevant increase upon stressing
+Note: Only modifications > 0.5% are reported
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="20" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2 HIS2 ABDEG - Modifications (deam/isoD)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>18E2 HIS2 ABDEG</th>
+<th>18E2 HIS2 ABDEG T6w</th>
+</tr>
+<tr>
+<td rowspan="2">EVQLLESGGGLVQPGGSLR</td>
+<td rowspan="2">HC(1-19)</td>
+<td>Deamidation</td>
+<td>2.5</td>
+<td>2.0</td>
+</tr>
+<tr>
+<td></td>
+<td>97.5</td>
+<td>98.0</td>
+</tr>
+<tr>
+<td rowspan="2">NTLYLQMNSLR</td>
+<td rowspan="2">HC(77-87)</td>
+<td rowspan="2">Deamidation</td>
+<td>1.5</td>
+<td>2.2</td>
+</tr>
+<tr>
+<td>98.5</td>
+<td>97.8</td>
+</tr>
+<tr>
+<td rowspan="2">FNWYVDGVEVHNAK</td>
+<td rowspan="2">HC(284-297)</td>
+<td>IsoD</td>
+<td>0.8</td>
+<td>1.7</td>
+</tr>
+<tr>
+<td></td>
+<td>99.2</td>
+<td>98.3</td>
+</tr>
+<tr>
+<td rowspan="3">VVSVLTVLHQDWLNGK</td>
+<td rowspan="3">HC(311-326)</td>
+<td>Deamidation</td>
+<td>0.9</td>
+<td>1.5</td>
+</tr>
+<tr>
+<td></td>
+<td>97.1</td>
+<td>96.2</td>
+</tr>
+<tr>
+<td>Succinimide</td>
+<td>2.0</td>
+<td>2.3</td>
+</tr>
+<tr>
+<td rowspan="2">NQVSLTCLVK</td>
+<td rowspan="2">HC(370-379)</td>
+<td>Deamidation</td>
+<td>4.0</td>
+<td>4.9</td>
+</tr>
+<tr>
+<td></td>
+<td>96.0</td>
+<td>95.1</td>
+</tr>
+<tr>
+<td rowspan="2">GFYPSDIAVEWESNGQPENNYK</td>
+<td rowspan="2">HC(380-401)</td>
+<td>Deamidation</td>
+<td>6.1</td>
+<td>24.5</td>
+</tr>
+<tr>
+<td></td>
+<td>93.9</td>
+<td>75.5</td>
+</tr>
+<tr>
+<td>TTPPVLDSDGSFFLYSK</td>
+<td>HC(402-418)</td>
+<td>IsoD</td>
+<td>0.7 99.3</td>
+<td>1.6 98.4</td>
+</tr>
+</table>
+
+BOLD: relevant increase upon stressing
+
+Note: Only modifications > 0.5% are reported
+
+
+<figure>
+</figure>
+
+
+RIC
+biologics
+
+<!-- PageNumber="21" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+### Results 18E2 HIS2 ABDEG - Modifications (pyroE)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>18E2 HIS2 ABDEG</th>
+<th>18E2 HIS2 ABDEG T6w</th>
+</tr>
+<tr>
+<td>EVQLLESGGGLVQPGGSLR</td>
+<td>HC(1-19)</td>
+<td>PyroE</td>
+<td>2.2 97.8</td>
+<td>11.1 89.0</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="22" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2 HIS2 ABDEG - Modifications
+
+
+### >HEAVY CHAIN : 18E2HIS2
+
+EVOLLESGGGLVQPGGSLRLSCAASGFTFSSYVMHWVRQAPGKGLEWVSSIYHDGSHTYYADFVKGRFTISRDNSKNTLYLQ
+MNSLRAEDTAVYYCAKGTSYSGSYYYTDPFFGSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
+VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
+PSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
+KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
+GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPGK
+
+
+### >LIGHT CHAIN : 18E2HIS2
+
+SSELTQDPAVSVALGQTVRITCQGDRLGSRYIHWYQQKPGQAPVLVIYDDDRRPSGIPDRFSGSSSGNTASLTITGAQAEDE
+ADYYCOSADSSGNPVFGGGTQLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTT
+PSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageFooter="RED: relevant increase upon stressing" -->
+<!-- PageNumber="23" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2VL HIS LALA ABDEG - Identity
+
+
+<table>
+<tr>
+<th>RT</th>
+<th>Mass</th>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Tgt Seq Mass</th>
+<th>Diff (Bio, ppm)</th>
+<th>Pred Mods</th>
+</tr>
+<tr>
+<td>23.53</td>
+<td>1895.0099</td>
+<td>EVQLLESGGGLVQPGGSLR</td>
+<td>HC(001-019)</td>
+<td>1895.0113</td>
+<td>-0.71</td>
+<td></td>
+</tr>
+<tr>
+<td>30.89</td>
+<td>2154.9844</td>
+<td>LSCAASGFTFSSYVMSWVR</td>
+<td>HC(020-038)</td>
+<td>2154.9867</td>
+<td>-1.06</td>
+<td></td>
+</tr>
+<tr>
+<td>33.75</td>
+<td>5191.4234</td>
+<td>LSCAASGFTFSSYVMSWVRQAPGKGLEWVSSIYHDGSHTYYADFVK</td>
+<td>HC(020-065)</td>
+<td>5191.4273</td>
+<td>-0.77</td>
+<td></td>
+</tr>
+<tr>
+<td>6.08</td>
+<td>499.2755</td>
+<td>QAPGK</td>
+<td>HC(039-043)</td>
+<td>499.2755</td>
+<td>0.01</td>
+<td></td>
+</tr>
+<tr>
+<td>25.60</td>
+<td>2573.1851</td>
+<td>GLEWVSSIYHDGSHTYYADFVK</td>
+<td>HC(044-065)</td>
+<td>2573.1863</td>
+<td>-0.48</td>
+<td></td>
+</tr>
+<tr>
+<td>25.93</td>
+<td>3390.6398</td>
+<td>GLEWVSSIYHDGSHTYYADFVKGRFTISR</td>
+<td>HC(044-072)</td>
+<td>3390.6422</td>
+<td>-0.72</td>
+<td></td>
+</tr>
+<tr>
+<td>1.98</td>
+<td>231.1327</td>
+<td>GR</td>
+<td>HC(066-067)</td>
+<td>231.1331</td>
+<td>-1.81</td>
+<td></td>
+</tr>
+<tr>
+<td>15.94</td>
+<td>835.4666</td>
+<td>GRFTISR</td>
+<td>HC(066-072)</td>
+<td>835.4664</td>
+<td>0.19</td>
+<td></td>
+</tr>
+<tr>
+<td>16.06</td>
+<td>622.3441</td>
+<td>FTISR</td>
+<td>HC(068-072)</td>
+<td>622.3439</td>
+<td>0.33</td>
+<td></td>
+</tr>
+<tr>
+<td>22.54</td>
+<td>1351.6916</td>
+<td>NTLYLQMNSLR</td>
+<td>HC(077-087)</td>
+<td>1351.6918</td>
+<td>-0.13</td>
+<td></td>
+</tr>
+<tr>
+<td>15.52</td>
+<td>1289.5586</td>
+<td>AEDTAVYYCAK</td>
+<td>HC(088-098)</td>
+<td>1289.5598</td>
+<td>-0.93</td>
+<td></td>
+</tr>
+<tr>
+<td>28.17</td>
+<td>3400.5377</td>
+<td>GTSYSGSYYYTDPFFGSWGQGTLVTVSSASTK</td>
+<td>HC(099-130)</td>
+<td>3400.5412</td>
+<td>-1.03</td>
+<td></td>
+</tr>
+<tr>
+<td>22.50</td>
+<td>1185.6390</td>
+<td>GPSVFPLAPSSK</td>
+<td>HC(131-142)</td>
+<td>1185.6394</td>
+<td>-0.35</td>
+<td></td>
+</tr>
+<tr>
+<td>20.37</td>
+<td>1320.6709</td>
+<td>STSGGTAALGCLVK</td>
+<td>HC(143-156)</td>
+<td>1320.6708</td>
+<td>0.11</td>
+<td></td>
+</tr>
+<tr>
+<td>31.67</td>
+<td>8014.9558</td>
+<td>STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK</td>
+<td>HC(143-219)</td>
+<td>8014.9674</td>
+<td>-1.44</td>
+<td></td>
+</tr>
+<tr>
+<td>30.98</td>
+<td>6712.2902</td>
+<td>DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK</td>
+<td>HC(157-219)</td>
+<td>6712.3072</td>
+<td>-2.53</td>
+<td></td>
+</tr>
+<tr>
+<td>3.78</td>
+<td>360.2002</td>
+<td>VDK</td>
+<td>HC(220-222)</td>
+<td>360.2009</td>
+<td>-1.91</td>
+<td></td>
+</tr>
+<tr>
+<td>3.06</td>
+<td>488.2956</td>
+<td>VDKK</td>
+<td>HC(220-223)</td>
+<td>488.2959</td>
+<td>-0.57</td>
+<td></td>
+</tr>
+<tr>
+<td>8.41</td>
+<td>599.3647</td>
+<td>KVEPK</td>
+<td>HC(223-227)</td>
+<td>599.3643</td>
+<td>0.73</td>
+<td></td>
+</tr>
+<tr>
+<td>7.89</td>
+<td>471.2691</td>
+<td>VEPK</td>
+<td>HC(224-227)</td>
+<td>471.2693</td>
+<td>-0.5</td>
+<td></td>
+</tr>
+<tr>
+<td>2.06</td>
+<td>508.1944</td>
+<td>SCDK</td>
+<td>HC(228-231)</td>
+<td>508.1952</td>
+<td>-1.57</td>
+<td></td>
+</tr>
+<tr>
+<td>22.03</td>
+<td>3249.5197</td>
+<td>SCDKTHTCPPCPAPEAAGGPSVFLFPPKPK</td>
+<td>HC(228-257)</td>
+<td>3249.5410</td>
+<td>-6.55</td>
+<td></td>
+</tr>
+<tr>
+<td>24.58</td>
+<td>2759.3550</td>
+<td>THTCPPCPAPEAAGGPSVFLFPPKPK</td>
+<td>HC(232-257)</td>
+<td>2759.3564</td>
+<td>-0.5</td>
+<td></td>
+</tr>
+<tr>
+<td>17.75</td>
+<td>880.4653</td>
+<td>DTLYITR</td>
+<td>HC(258-264)</td>
+<td>880.4654</td>
+<td>-0.18</td>
+<td></td>
+</tr>
+<tr>
+<td>22.03</td>
+<td>2166.0157</td>
+<td>EPEVTCVVVDVSHEDPEVK</td>
+<td>HC(265-283)</td>
+<td>2166.0151</td>
+<td>0.29</td>
+<td></td>
+</tr>
+<tr>
+<td>22.35</td>
+<td>1676.7944</td>
+<td>FNWYVDGVEVHNAK</td>
+<td>HC(284-297)</td>
+<td>1676.7947</td>
+<td>-0.16</td>
+<td></td>
+</tr>
+<tr>
+<td>4.64</td>
+<td>500.3070</td>
+<td>TKPR</td>
+<td>HC(298-301)</td>
+<td>500.3071</td>
+<td>-0.22</td>
+<td></td>
+</tr>
+<tr>
+<td>11.96</td>
+<td>1188.5044</td>
+<td>EEQYNSTYR</td>
+<td>HC(302-310)</td>
+<td>1188.5047</td>
+<td>-0.27</td>
+<td></td>
+</tr>
+<tr>
+<td>11.18</td>
+<td>2633.0350</td>
+<td>EEQYNSTYR</td>
+<td>HC(302-310)</td>
+<td>2633.0386</td>
+<td>-1.39</td>
+<td>G0F</td>
+</tr>
+<tr>
+<td>28.70</td>
+<td>1806.9988</td>
+<td>VVSVLTVLHQDWLNGK</td>
+<td>HC(311-326)</td>
+<td>1806.9992</td>
+<td>-0.26</td>
+<td></td>
+</tr>
+<tr>
+<td>27.74</td>
+<td>2227.1974</td>
+<td>VVSVLTVLHQDWLNGKEYK</td>
+<td>HC(311-329)</td>
+<td>2227.2001</td>
+<td>-1.23</td>
+<td></td>
+</tr>
+<tr>
+<td>6.58</td>
+<td>438.2111</td>
+<td>EYK</td>
+<td>HC(327-329)</td>
+<td>438.2115</td>
+<td>-0.78</td>
+<td></td>
+</tr>
+<tr>
+<td>1.98</td>
+<td>306.1358</td>
+<td>CK</td>
+<td>HC(330-331)</td>
+<td>306.1362</td>
+<td>-1.29</td>
+<td></td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+<!-- PageFooter="biologics" -->
+
+</figure>
+
+
+<!-- PageNumber="24" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2VL HIS LALA ABDEG - Identity
+
+
+<table>
+<tr>
+<th>RT</th>
+<th>Mass</th>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Tgt Seq Mass</th>
+<th>Diff (Bio, ppm)</th>
+<th>Pred Mods</th>
+</tr>
+<tr>
+<td>3.05</td>
+<td>446.2487</td>
+<td>VSNK</td>
+<td>HC(332-335)</td>
+<td>446.2489</td>
+<td>-0.55</td>
+<td></td>
+</tr>
+<tr>
+<td>28.16</td>
+<td>1695.0096</td>
+<td>VSNKALPAPIEKTISK</td>
+<td>HC(332-347)</td>
+<td>1694.9931</td>
+<td>9.77</td>
+<td></td>
+</tr>
+<tr>
+<td>18.00</td>
+<td>837.4958</td>
+<td>ALPAPIEK</td>
+<td>HC(336-343)</td>
+<td>837.4960</td>
+<td>-0.21</td>
+<td></td>
+</tr>
+<tr>
+<td>8.04</td>
+<td>447.2690</td>
+<td>TISK</td>
+<td>HC(344-347)</td>
+<td>447.2693</td>
+<td>-0.75</td>
+<td></td>
+</tr>
+<tr>
+<td>6.37</td>
+<td>655.3759</td>
+<td>AKGQPR</td>
+<td>HC(348-353)</td>
+<td>655.3766</td>
+<td>-1.07</td>
+<td></td>
+</tr>
+<tr>
+<td>5.31</td>
+<td>456.2435</td>
+<td>GQPR</td>
+<td>HC(350-353)</td>
+<td>456.2445</td>
+<td>-2.09</td>
+<td></td>
+</tr>
+<tr>
+<td>18.66</td>
+<td>1285.6660</td>
+<td>EPQVYTLPPSR</td>
+<td>HC(354-364)</td>
+<td>1285.6667</td>
+<td>-0.5</td>
+<td></td>
+</tr>
+<tr>
+<td>19.69</td>
+<td>1871.9618</td>
+<td>EPQVYTLPPSRDELTK</td>
+<td>HC(354-369)</td>
+<td>1871.9629</td>
+<td>-0.59</td>
+<td></td>
+</tr>
+<tr>
+<td>10.34</td>
+<td>604.3071</td>
+<td>DELTK</td>
+<td>HC(365-369)</td>
+<td>604.3068</td>
+<td>0.48</td>
+<td></td>
+</tr>
+<tr>
+<td>21.72</td>
+<td>1160.6226</td>
+<td>NQVSLTCLVK</td>
+<td>HC(370-379)</td>
+<td>1160.6224</td>
+<td>0.17</td>
+<td></td>
+</tr>
+<tr>
+<td>24.23</td>
+<td>2543.1202</td>
+<td>GFYPSDIAVEWESNGQPENNYK</td>
+<td>HC(380-401)</td>
+<td>2543.1241</td>
+<td>-1.55</td>
+<td></td>
+</tr>
+<tr>
+<td>25.94</td>
+<td>1872.9129</td>
+<td>TTPPVLDSDGSFFLYSK</td>
+<td>HC(402-418)</td>
+<td>1872.9146</td>
+<td>-0.88</td>
+<td></td>
+</tr>
+<tr>
+<td>12.41</td>
+<td>574.3326</td>
+<td>LTVDK</td>
+<td>HC(419-423)</td>
+<td>574.3326</td>
+<td>-0.09</td>
+<td></td>
+</tr>
+<tr>
+<td>16.06</td>
+<td>261.1445</td>
+<td>SR</td>
+<td>HC(424-425)</td>
+<td>261.1437</td>
+<td>2.98</td>
+<td></td>
+</tr>
+<tr>
+<td>23.23</td>
+<td>2019.9271</td>
+<td>WQQGNVFSCSVMHEALK</td>
+<td>HC(426-442)</td>
+<td>2019.9295</td>
+<td>-1.2</td>
+<td></td>
+</tr>
+<tr>
+<td>24.16</td>
+<td>2824.3141</td>
+<td>WQQGNVFSCSVMHEALKFHYTQK</td>
+<td>HC(426-448)</td>
+<td>2824.3214</td>
+<td>-2.58</td>
+<td></td>
+</tr>
+<tr>
+<td>12.51</td>
+<td>822.4014</td>
+<td>FHYTQK</td>
+<td>HC(443-448)</td>
+<td>822.4024</td>
+<td>-1.25</td>
+<td></td>
+</tr>
+<tr>
+<td>18.196</td>
+<td>659.3479</td>
+<td>SLSLSPG</td>
+<td>HC(449-455)</td>
+<td>659.3490</td>
+<td>-1.68</td>
+<td></td>
+</tr>
+<tr>
+<td>16.87</td>
+<td>787.4415</td>
+<td>SLSLSPGK</td>
+<td>HC(449-456)</td>
+<td>787.4440</td>
+<td>-3.09</td>
+<td></td>
+</tr>
+<tr>
+<td>22.65</td>
+<td>1957.0108</td>
+<td>SSELTQDPAVSVALGQTVR</td>
+<td>LC(001-019)</td>
+<td>1957.0116</td>
+<td>-0.45</td>
+<td></td>
+</tr>
+<tr>
+<td>8.99</td>
+<td>848.3805</td>
+<td>ITCQGDR</td>
+<td>LC(020-026)</td>
+<td>848.3811</td>
+<td>-0.67</td>
+<td></td>
+</tr>
+<tr>
+<td>8.03</td>
+<td>431.2489</td>
+<td>LGSR</td>
+<td>LC(027-030)</td>
+<td>431.2492</td>
+<td>-0.69</td>
+<td></td>
+</tr>
+<tr>
+<td>24.59</td>
+<td>2703.3425</td>
+<td>YIHWYQQKPGQAPVLVIYDDDR</td>
+<td>LC(031-052)</td>
+<td>2703.3445</td>
+<td>-0.75</td>
+<td></td>
+</tr>
+<tr>
+<td>23.77</td>
+<td>3581.8139</td>
+<td>YIHWYQQKPGQAPVLVIYDDDRRPSGIPDR</td>
+<td>LC(031-060)</td>
+<td>3581.8168</td>
+<td>-0.82</td>
+<td></td>
+</tr>
+<tr>
+<td>13.04</td>
+<td>896.4835</td>
+<td>RPSGIPDR</td>
+<td>LC(053-060)</td>
+<td>896.4828</td>
+<td>0.79</td>
+<td></td>
+</tr>
+<tr>
+<td>25.11</td>
+<td>5127.3093</td>
+<td>FSGSSSGNTASLTITGAQAEDEADYYCQSADSSGNPVFGGGTQLTVLGQPK</td>
+<td>LC(061-111)</td>
+<td>5127.3164</td>
+<td>-1.38</td>
+<td></td>
+</tr>
+<tr>
+<td>23.58</td>
+<td>1985.0087</td>
+<td>AAPSVTLFPPSSEELQANK</td>
+<td>LC(112-130)</td>
+<td>1985.0106</td>
+<td>-0.96</td>
+<td></td>
+</tr>
+<tr>
+<td>34.69</td>
+<td>4177.1399</td>
+<td>AAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWK</td>
+<td>LC(112-150)</td>
+<td>4177.1446</td>
+<td>-1.11</td>
+<td></td>
+</tr>
+<tr>
+<td>33.08</td>
+<td>2210.1433</td>
+<td>ATLVCLISDFYPGAVTVAWK</td>
+<td>LC(131-150)</td>
+<td>2210.1446</td>
+<td>-0.59</td>
+<td></td>
+</tr>
+<tr>
+<td>10.21</td>
+<td>702.3546</td>
+<td>ADSSPVK</td>
+<td>LC(151-157)</td>
+<td>702.3548</td>
+<td>-0.26</td>
+<td></td>
+</tr>
+<tr>
+<td>11.55</td>
+<td>989.5026</td>
+<td>AGVETTTPSK</td>
+<td>LC(158-167)</td>
+<td>989.5029</td>
+<td>-0.31</td>
+<td></td>
+</tr>
+<tr>
+<td>1.96</td>
+<td>589.2812</td>
+<td>QSNNK</td>
+<td>LC(168-172)</td>
+<td>589.2820</td>
+<td>-1.34</td>
+<td></td>
+</tr>
+<tr>
+<td>24.35</td>
+<td>1742.8504</td>
+<td>YAASSYLSLTPEQWK</td>
+<td>LC(173-187)</td>
+<td>1742.8516</td>
+<td>-0.67</td>
+<td></td>
+</tr>
+<tr>
+<td>2.10</td>
+<td>398.2022</td>
+<td>SHR</td>
+<td>LC(188-190)</td>
+<td>398.2026</td>
+<td>-1.16</td>
+<td></td>
+</tr>
+<tr>
+<td>13.39</td>
+<td>1710.7512</td>
+<td>SYSCQVTHEGSTVEK</td>
+<td>LC(191-205)</td>
+<td>1710.7519</td>
+<td>-0.45</td>
+<td></td>
+</tr>
+<tr>
+<td>11.73</td>
+<td>863.3683</td>
+<td>TVAPTECS</td>
+<td>LC(206-213)</td>
+<td>863.3695</td>
+<td>-1.39</td>
+<td></td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="25" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2VL HIS LALA ABDEG - Identity
+
+
+### >HEAVY CHAIN: 18E2VLHIS LALA ABDEG
+
+EVOLLESGGGLVQPGGSLRLSCAASGFTFSSYVMSWVRQAPGKGLEWVSSIYHDGSHTYYADFVKGRFTISRDNSKNTLYLOMN
+SLRAEDTAVYYCAKGTSYSGSYYYTDPFFGSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
+SGALTSGVHTFPAVLOSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF
+PPKPKDTLYITREPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
+LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
+VDKSRWQQGNVFSCSVMHEALKFHYTOKSLSLSPGK
+
+
+### >LIGHT CHAIN: 18E2VLHIS LALA ABDEG
+
+SSELTQDPAVSVALGQTVRITCQGDRLGSRYIHWYQQKPGQAPVLVIYDDDRRPSGIPDRFSGSSSGNTASLTITGAQAEDEAD
+YYCOSADSSGNPVFGGGTQLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQ
+SNNKYAASSYLSLTPEQWKSHRSYSCOVTHEGSTVEKTVAPTECS
+
+Sequence coverage of 99.4%
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="26" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2VL HIS LALA ABDEG - Modifications (oxidation)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>18E2VL LALA ABDEG</th>
+<th>18E2VL LALA ABDEG T6w</th>
+</tr>
+<tr>
+<td>WQQGNVFSCSVMHEALK</td>
+<td>HC(426-442)</td>
+<td>Oxidation</td>
+<td>2.8 97.2</td>
+<td>13.3 86.7</td>
+</tr>
+</table>
+
+BOLD: relevant increase upon stressing
+Note: Only modifications > 0.5% are reported
+
+
+<figure>
+</figure>
+
+
+RIC
+biologics
+
+<!-- PageNumber="27" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2VL HIS LALA ABDEG - Modifications (deam/isoD)
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>18E2VL LALA ABDEG</th>
+<th>18E2VL LALA ABDEG T6w</th>
+</tr>
+<tr>
+<td rowspan="2">EVQLLESGGGLVQPGGSLR</td>
+<td rowspan="2">HC(1-19)</td>
+<td>Deamidation</td>
+<td>2.4</td>
+<td>2.4</td>
+</tr>
+<tr>
+<td></td>
+<td>97.6</td>
+<td>97.6</td>
+</tr>
+<tr>
+<td rowspan="2">NTLYLQMNSLR</td>
+<td rowspan="2">HC(77-87)</td>
+<td rowspan="2">Deamidation</td>
+<td>1.9</td>
+<td>3.2</td>
+</tr>
+<tr>
+<td>98.1</td>
+<td>96.8</td>
+</tr>
+<tr>
+<td rowspan="2">FNWYVDGVEVHNAK</td>
+<td rowspan="2">HC(284-297)</td>
+<td>IsoD</td>
+<td>0.7</td>
+<td>1.7</td>
+</tr>
+<tr>
+<td></td>
+<td>99.3</td>
+<td>98.3</td>
+</tr>
+<tr>
+<td rowspan="3">VVSVLTVLHQDWLNGK</td>
+<td rowspan="3">HC(311-326)</td>
+<td>Deamidation</td>
+<td>0.7</td>
+<td>1.7</td>
+</tr>
+<tr>
+<td></td>
+<td>96.9</td>
+<td>95.8</td>
+</tr>
+<tr>
+<td>Succinimide</td>
+<td>2.4</td>
+<td>2.5</td>
+</tr>
+<tr>
+<td rowspan="2">NQVSLTCLVK</td>
+<td rowspan="2">HC(370-379)</td>
+<td>Deamidation</td>
+<td>3.7</td>
+<td>5.9</td>
+</tr>
+<tr>
+<td></td>
+<td>96.3</td>
+<td>94.1</td>
+</tr>
+<tr>
+<td rowspan="2">GFYPSDIAVEWESNGQPENNYK</td>
+<td rowspan="2">HC(380-401)</td>
+<td rowspan="2">Deamidation</td>
+<td>6.9</td>
+<td>27.4</td>
+</tr>
+<tr>
+<td>93.1</td>
+<td>72.6</td>
+</tr>
+<tr>
+<td>TTPPVLDSDGSFFLYSK</td>
+<td>HC(402-418)</td>
+<td>IsoD</td>
+<td>1.0 99.0</td>
+<td>1.5 98.5</td>
+</tr>
+</table>
+
+BOLD: relevant increase upon stressing
+
+Note: Only modifications > 0.5% are reported
+
+
+<figure>
+</figure>
+
+
+RIC
+biologics
+
+<!-- PageNumber="28" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+<!-- PageHeader="Results 18E2VL HIS LALA ABDEG - Modifications (pyroE)" -->
+
+
+<table>
+<tr>
+<th>Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>18E2VL LALA ABDEG</th>
+<th>18E2VL LALA ABDEG T6w</th>
+</tr>
+<tr>
+<td>EVQLLESGGGLVQPGGSLR</td>
+<td>HC(1-19)</td>
+<td>PyroE</td>
+<td>2.1 97.9</td>
+<td>11.1 88.9</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="29" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results 18E2VL HIS LALA ABDEG - Modifications
+
+
+### >HEAVY CHAIN: 18E2VLHIS
+
+EVOLLESGGGLVQPGGSLRLSCAASGFTFSSYVMSWVRQAPGKGLEWVSSIYHDGSHTYYADFVKGRFTISRDNSKNTLYLQMN
+SLRAEDTAVYYCAKGTSYSGSYYYTDPFFGSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
+SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF
+PPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA
+LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
+VDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPGK
+
+
+### >LIGHT CHAIN : 18E2VLHIS
+
+SSELTQDPAVSVALGQTVRITCQGDRLGSRYIHWYQQKPGQAPVLVIYDDDRRPSGIPDRFSGSSSGNTASLTITGAQAEDEAD
+YYCOSADSSGNPVFGGGTQLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQ
+SNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="30" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Conclusions
+
+· Near complete sequence coverage obtained for all molecules studied
+
+. Nevertheless, partially digested material observed in samples 18E2HIS2-ABDEG and 18E2VLHIS-LALA-
+ABDEG (not hampering data interpretation)
+
+· Peptide mapping of Ligelizumab mAB 37reveals
+
+· 4 sites prone to oxidation upon stressing of which three located in the variable part of the heavy chain
+
+· 1 site located in the conserved region of the heavy chain prone to deamidation upon stressing
+
+· Heavy chain N-terminus is fully cyclic (pyroE) and C-terminus predominantly lysine truncated
+
+· Peptide mapping of 18E2HIS2-ABDEG and 18E2VLHIS-LALA-ABDEG reveals
+
+· 1 site located in the conserved region of the heavy chain prone to oxidation upon stressing
+
+· 1 site located in the conserved region of the heavy chain prone to deamidation upon stressing
+
+· Partial cyclization of the heavy chain N-terminus observed upon stressing
+
+· No major liabilities detected in the CDRs upon stressing
+
+· Peptide mapping of OMA VH15G55H VL3S31H reveals
+
+· Complete degradation upon storage
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="31" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Signature section RIC
+
+
+### Author
+
+
+<table>
+<tr>
+<td>Gianni Vandenborre</td>
+<td>Date: 15 FEB 2021</td>
+</tr>
+<tr>
+<td>Sr Scientist Biologics | Project Manager</td>
+<td>10 Signature:</td>
+</tr>
+<tr>
+<td colspan="2">Reviewer</td>
+</tr>
+<tr>
+<td>An Cerdobbel Ph.D.</td>
+<td>Date: 16 FEB 2021</td>
+</tr>
+<tr>
+<td>Head of Biologics Department</td>
+<td>Signature: Cedobre</td>
+</tr>
+<tr>
+<td colspan="2">Approver</td>
+</tr>
+<tr>
+<td>Koen Sandra Ph.D.</td>
+<td>Date: 1 MAR 2021</td>
+</tr>
+<tr>
+<td>Scientific Director</td>
+<td>Signature:</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="32" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Version control
+
+
+<table>
+<tr>
+<th>Version</th>
+<th>Date of issue</th>
+<th>Reason for version update</th>
+</tr>
+<tr>
+<td>01</td>
+<td>30-JUL-2020</td>
+<td>First issue</td>
+</tr>
+</table>
+
+
+<figure>
+
+<!-- PageFooter="RIC" -->
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="33" -->
+<!-- PageBreak -->
+
+
+<figure>
+
+RIC
+
+biologics
+
+</figure>
+
+
+YOUR MOLECULE. OUR ANALYTICS. NO SECRETS.
+
+<!-- PageFooter="www.RICbiologics.com" -->

logs/di_content/di_content_20250604_141519.txt

@@ -0,0 +1,2110 @@
+# ARGX DISCOVERY: EVALUATION OF LIABILITIES IN VH AND VL REGION OF TWO CONSTRUCTS
+
+Argenx - P3016_R04_v01
+
+
+<figure>
+
+RIC
+
+biologics
+
+</figure>
+
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+<!-- PageHeader="Table of contents" -->
+
+l Project information
+
+Scope
+
+l Test samples
+
+l
+Method
+
+l
+Results
+
+· P052_OA-02A10-GLLiab4His1_0-hlgG1-CH2-CH3-LALAPG-ABDEG-FJB_2024-01-
+26_002
+
+· P052_OA-02A10-GLLiab4+Liab11-His1_0-hlgG1-CH2-CH3-LALAPG-ABDEG-
+FJB_2024-01-26_001
+
+l
+Conclusions
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="2" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Project information
+
+
+<table>
+<tr>
+<td>Sales quote:</td>
+<td>SQ20202722</td>
+</tr>
+<tr>
+<td>l Project code:</td>
+<td>P3016</td>
+</tr>
+<tr>
+<td>l LNB number:</td>
+<td>2023.040</td>
+</tr>
+<tr>
+<td>l Project responsible:</td>
+<td>Nathan Cardon</td>
+</tr>
+<tr>
+<td>l Report name:</td>
+<td>P3016_R04_v01</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="3" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+Scope
+
+l This report describes the results of a liability assessment for two Argenx
+discovery constructs. Non-stressed and temperature-stressed samples
+stored for four weeks at 37℃ were evaluated by reduced protein RPLC-UV-
+MS and peptide map analysis.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="4" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Test samples
+
+The samples used in this study are listed below
+
+
+<table>
+<tr>
+<th>Construct</th>
+<th>Storage condition</th>
+<th>Concentration (mg/ml)</th>
+</tr>
+<tr>
+<td rowspan="2">P052_OA-02A10-GLLiab4His1_0-hIgG1-CH2- CH3-LALAPG-ABDEG-FJB_2024-01-26_002</td>
+<td>T0</td>
+<td>1.0</td>
+</tr>
+<tr>
+<td>T4w 37°℃</td>
+<td>1.0</td>
+</tr>
+<tr>
+<td rowspan="2">P052_OA-02A10-GLLiab4+Liab11-His1_0- hIgG1-CH2-CH3-LALAPG-ABDEG-FJB_2024- 01-26_001</td>
+<td>T0</td>
+<td>1.0</td>
+</tr>
+<tr>
+<td>T4w 37℃</td>
+<td>1.0</td>
+</tr>
+</table>
+
+
+Note: all antibodies are in an One-Armed (OA) format
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="5" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Method: Protein analysis by RPLC-(UV)-MS
+
+l The samples were reduced by incubation with DTT while in denaturing
+conditions. The samples were analyzed using a C8 RPLC column on a 1290
+Infinity UHPLC system coupled to a 6530 Q-TOF mass spectrometer (both
+from Agilent Technologies).
+
+l RPLC was performed with trifluoroacetic acid (TFA) as ion pairing additive,
+and with H2O and acetonitrile as mobile phases.
+
+l Data acquisition and processing were performed with BioConfirm
+MassHunter 7.0 (Agilent Technologies). UV 280 nm and MS data were
+acquired simultaneously.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="6" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Method: Peptide map analysis in reducing conditions
+
+l
+Prior to digestion, the samples were reduced using dithiothreitol (DTT), and alkylated
+with iodoacetamide (IAA). The samples were digested using trypsin as protease.
+
+l The digests were analyzed on RPLC-MS using a C18 RPLC column. RPLC was performed
+with formic acid (FA) as additive, and with H2O and acetonitrile as mobile phases. The
+analyses were performed on a 1290 Infinity UHPLC system (Agilent Technologies) coupled
+to a 6540 Q-TOF Mass Spectrometer (Agilent Technologies) operated in MS and MS/MS
+mode.
+
+l Data processing was performed using BioConfirm 10.0 and MassHunter 7.0 (Agilent
+Technologies).
+
+l Measured signals were matched onto the sequence. Identification was based primarily
+on MS-only data. Enzyme specified was trypsin (C-terminal cleavage at lysine or arginine)
+and 0-2 missed cleavages were allowed. N-terminal cyclization (pyroglutamate from E/Q),
+D isomerization, N/Q deamidation, M/W oxidation and N-glycosylation were considered
+as variable modifications while cysteine carbamidomethylation (sample preparation
+related) was considered as fixed modification. Peak areas from extracted ion
+chromatograms (EICs) were used for quantifying modifications.
+
+l Note that peptide map data processing was focused on the variable regions of the
+constructs.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+biologics
+
+<!-- PageNumber="7" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+P052_OA-02A10-GLLIAB4HIS1_0-HIGG1-CH2-CH3-LALAPG-ABDEG-
+FJB_2024-01-26_002
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: AA sequence
+
+l
+
+AA sequence of GLLiab4_Heavy_Knob_LALAPG_ABDEG (MW (G0F): 50740.4 Da)
+
+EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYVMSWVRQAPGKGLEWVSHIQGGGITSYADSVKGRFTISRDNSKNTLYLQ
+MNSLRAEDTAVYYCAKWLVDYGLGNRGSMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV
+SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPS
+VFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
+KVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
+FLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPG
+
+l AA sequence of GLHis1_Light_CL1 (MW (pyroQ): 23646.43 Da)
+
+QAVLTQPPSLSASPGASARLTCSLSSGTIVHGYHINWYQQKAGSPPRYLLRFYSDSNKHQGSGVPSRFSGSKDASANAGILLIS
+GLQPEDEADYYCGTYHSNTGTYVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVK
+AGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
+
+l AA sequence of CH2_CH3_Hole_LALAPG_ABDEG (MW (G0F) 26719.1 Da)
+
+DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
+VSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNG
+QPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLS
+
+
+<figure>
+
+RIC
+
+<!-- PageFooter="biologics" -->
+
+</figure>
+
+
+<table>
+<tr>
+<td>Blue:</td>
+<td>VH and VL</td>
+</tr>
+<tr>
+<td>Green:</td>
+<td>N-glycosylation site</td>
+</tr>
+<tr>
+<td>Red:</td>
+<td>N-terminal cyclization</td>
+</tr>
+</table>
+
+
+<!-- PageNumber="9" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: reduced RPLC-UV-MS
+
+
+### l
+
+
+#### Overlays of the UV214nm profiles
+
+
+<figure>
+
+x10 2
+
+DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P3016_Molecule1_W0_C8_19MAR2024.d
+
+HC_Knob
+
+6.5
+
+T0
+
+6
+
+T4w 37℃
+
+x: Unknown fragment (13463 Da)
+
+0: GG clip (G144-G452)
+
+6
+
+Hole
+
+y: Intact LC without pyroQ
+
+1: GG clip (G55-G452)
+
+5.5
+
+z: Intact LC (pyroQ) + LC fragments:
+
+2: NS clip (73-452)
+
+5
+
+b
+
+LC
+
+N terminal Q loss
+
+3: - 17 Da (potentially HC +
+succinimide)
+
+C-terminal S loss
+
+4.5
+
+a: M oxidation: Hydroxy-y-lactam
+
+z
+
+b: Intact Hole
+
+C-terminal CS loss
+
+4: Traces oxidation (+32 Da)
+
+5: Oxidation (+16Da)
+
+4
+
+c: N-terminal DK loss
+
+6: Intact HC_knob
+
+3.5
+
+7: PyroE
+
+8: DP clip (E1-D276)
+
+3
+
+2.5
+
+2
+
+Unknown fragment*
+
+7
+
+1.5
+
+1
+
+c
+
+0.5
+
+x
+
+5
+
+a
+
+y
+
+0
+
+1
+
+2
+
+3
+
+4
+
+8
+
+0
+
+2
+
+3
+
+4
+
+5
+
+6
+
+7
+
+8
+
+9
+
+10
+
+Response Units vs. Acquisition Time (min)
+
+11
+
+12
+
+13
+
+14
+
+15
+
+16
+
+17
+
+18
+
+19
+
+20
+
+21
+
+22
+
+23
+
+24
+
+</figure>
+
+\* No MS data for this peak (falls outside the
+measurement window)
+
+Color legend:
+
+Black: clear identity on RPLC-UV-MS
+
+Blue: modification with clear trend visible on RPLC-UV-MS
+Blue: modification in variable region also confirmed in peptide
+mapping
+
+
+Grey: most likely method induced modification
+
+
+<figure>
+</figure>
+
+
+RIC
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="10" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: reduced RPLC-UV-MS
+
+
+### l Deconvoluted spectra of Hole, LC and HC_Knob (peak b, peak z and peak 6)
+
+×10 6
+
++ESI Scan (rt: 9.2-10.1 min, 89 scans) Frag=200.0V P3016_Molecule1_W0_C8_19MAR2024.d Deconvoluted (Isotope Width=10.0)
+
+1.25
+
+26717.06
+
+Theoretical mass Hole (G0F): 26719.1 Da
+
+1
+
+0.75
+
+0.5
+
+0.25
+
+0
+
+21343.69
+
+LL
+
+32883.11
+
++ESI Scan (rt: 12.9-13.5 min, 60 scans) Frag=200.0V P3016_Molecule1_W0_C8_19MAR2024.d Deconvoluted (Isotope Width=10.0)
+
+×10 6
+
+2.5
+
+23644.69
+
+Theoretical mass LC (pyroQ): 23646.4 Da
+
+2
+
+1.5
+
+1
+
+0.5
+
+15375.35
+
+25932.56
+
+30286.33
+
+0
+
+x10 5
+
++ESI Scan (rt: 16.4-21.6 min, 519 scans) Frag=200.0V P3016_Molecule1_W0_C8_19MAR2024.d Deconvoluted (Isotope Width=14.1)
+
+
+<figure>
+
+Theoretical mass HC_knob (G0F): 50740.4 Da
+
+50736.55
+
+0.8
+
+0.6
+
+0.4
+
+0.2
+
+0
+
+43809.72
+
+58410.62
+
+10000
+
+12500
+
+15000
+
+17500
+
+20000
+
+22500
+
+25000
+
+27500 30000
+
+32500 35000 375
+37500
+
+Counts vs. Deconvoluted Mass (amu)
+
+40000
+
+42500
+
+45000
+
+47500
+
+50000
+
+52500
+
+55000
+
+57500
+
+60000
+
+</figure>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="11" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l N-terminal and C-terminal modifications for HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w37℃</th>
+</tr>
+<tr>
+<td rowspan="2">EVOLVESGGGLVQPGGSLR</td>
+<td rowspan="2">HC(1-19)</td>
+<td></td>
+<td>98.8</td>
+<td>89.1</td>
+</tr>
+<tr>
+<td>PyroE</td>
+<td>1.2</td>
+<td>10.9</td>
+</tr>
+<tr>
+<td rowspan="3">QAVLTQPPSLSASPGASAR</td>
+<td rowspan="3">LC(1-19)</td>
+<td></td>
+<td>3.3</td>
+<td>0.0</td>
+</tr>
+<tr>
+<td>PyroQ</td>
+<td>96.7</td>
+<td>99.7</td>
+</tr>
+<tr>
+<td>N terminal Q loss</td>
+<td>0.0</td>
+<td>0.3</td>
+</tr>
+<tr>
+<td rowspan="3">TVAPTECS</td>
+<td rowspan="3">LC(216-223)</td>
+<td></td>
+<td>100.0</td>
+<td>99.6</td>
+</tr>
+<tr>
+<td>S loss</td>
+<td>0.0</td>
+<td>0.2</td>
+</tr>
+<tr>
+<td>CS loss</td>
+<td>0.0</td>
+<td>0.2</td>
+</tr>
+</table>
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="12" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l M/W oxidations in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w37℃</th>
+</tr>
+<tr>
+<td rowspan="2">LSCAASGFTFSSYVMSWVR</td>
+<td rowspan="2">HC(20-38)</td>
+<td></td>
+<td>97.1</td>
+<td>96.1</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>2.9</td>
+<td>3.9</td>
+</tr>
+<tr>
+<td rowspan="2">NTLYLQMNSLR</td>
+<td rowspan="2">HC(76-86)</td>
+<td></td>
+<td>98.3</td>
+<td>97.8</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>1.7</td>
+<td>2.2</td>
+</tr>
+<tr>
+<td rowspan="4">WLVDYGLGNR</td>
+<td rowspan="4">HC (098-107)</td>
+<td></td>
+<td>100.0</td>
+<td>97.2</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>0.0</td>
+<td>0.8</td>
+</tr>
+<tr>
+<td>Double oxidation</td>
+<td>0.0</td>
+<td>0.5</td>
+</tr>
+<tr>
+<td>+ 4 (Kynurenine)</td>
+<td>0.0</td>
+<td>1.5</td>
+</tr>
+<tr>
+<td rowspan="2">GSMDYWGQGTTVTVSSASTK</td>
+<td rowspan="2">HC(108-127)</td>
+<td></td>
+<td>97.1</td>
+<td>96.2</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>3.1</td>
+<td>4.3</td>
+</tr>
+</table>
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+biologics
+
+</figure>
+
+
+<!-- PageNumber="13" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l N/Q deamidation in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w 37℃</th>
+</tr>
+<tr>
+<td rowspan="2">GLEWVSHIQGGGITSYADSVK</td>
+<td rowspan="2">HC(44-64)</td>
+<td></td>
+<td>99.4</td>
+<td>96.3</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>0.6</td>
+<td>3.7</td>
+</tr>
+<tr>
+<td rowspan="2">DNSKNTLYLQMNSLR*</td>
+<td rowspan="2">HC(72-86)</td>
+<td></td>
+<td>98.6</td>
+<td>98.5</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>1.4</td>
+<td>1.5</td>
+</tr>
+<tr>
+<td rowspan="2">NTLYLQMNSLR</td>
+<td rowspan="2">HC(76-86)</td>
+<td></td>
+<td>99.2</td>
+<td>99.1</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>0.8</td>
+<td>0.9</td>
+</tr>
+<tr>
+<td rowspan="2">WLVDYGLGNR</td>
+<td rowspan="2">HC(98-107)</td>
+<td></td>
+<td>99.8</td>
+<td>98.6</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>0.2</td>
+<td>1.4</td>
+</tr>
+<tr>
+<td rowspan="2">DASANAGILLISGLQPEDEADYYCGTYHSNT GTYVFGGGTK</td>
+<td rowspan="2">LC(73-113)</td>
+<td></td>
+<td>97.7</td>
+<td>95.9</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>2.3</td>
+<td>4.1</td>
+</tr>
+</table>
+
+*The deamidation level on the misscleaved peptide was checked as the peptide DNSK has bad retention to have a reliable
+quantification. However, the misscleaved peptide has low abundance which can also lead to unreliable quantification of
+modifications.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+biologics
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+<!-- PageNumber="14" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l Isomerization events in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w 37℃</th>
+</tr>
+<tr>
+<td rowspan="2">WLVDYGLGNR</td>
+<td rowspan="2">HC(98-107)</td>
+<td></td>
+<td>99.7</td>
+<td>97.5</td>
+</tr>
+<tr>
+<td>isomerization</td>
+<td>0.3</td>
+<td>2.5</td>
+</tr>
+</table>
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+biologics
+
+<!-- PageNumber="15" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l Clipping events in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w 37℃</th>
+</tr>
+<tr>
+<td>GLEWVSHIQGGGITSYADSVK</td>
+<td>HC(44-64)</td>
+<td></td>
+<td>100.0</td>
+<td>99.7</td>
+</tr>
+<tr>
+<td>GLEWVSHIQGG</td>
+<td>HC(44-54)</td>
+<td rowspan="2">GG clip</td>
+<td>0.0</td>
+<td>0.3*</td>
+</tr>
+<tr>
+<td>GITSYADSVK</td>
+<td>HC(55-64)</td>
+<td>0.0</td>
+<td>0.8*</td>
+</tr>
+</table>
+
+*Due to differences in ionization efficiency between small and large peptides, the level of clipping reported here is most
+likely an overestimation.
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="16" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Conclusions
+
+l A potential unidentified clipping event may be present. Two peaks were present in the RPLC-UV-
+MS profile for which no identity was found. One peak (RT around 12 min) had a clear mass of
+13463 Da, while no mass could be retrieved for the second peak (RT around 3 min). Further
+experiments are required to find the origin of the unknown peaks.
+A less abundant clipping was found between G143G14 which falls just outside the variable region of
+HC_Knob but for sure may impact the functionality. Another clipping, this time in the variable
+region, was found between G54G55 . This clipping was confirmed via peptide mapping in the
+stressed sample in low amounts: < 1%.
+
+l Cyclization of the N-terminal glutamate on the HC_knob increased up to 10.9% during temperature
+stress (both present in RPLC-UV-MS and peptide map). Cyclization of the N-terminus on the LC
+reached completion after storage for four weeks at 37℃.
+
+l In addition, tryptic peptide peaks containing oxidation were found in the variable regions.
+Especially for W98 located on the HC_knob where the oxidation levels increased up to 2.8% after
+four weeks storage at 37℃. A second relevant increase in oxidation levels during the 4 weeks
+storage was found for HC(108-127): from 3.1 to 4.3%.
+
+l Deamidation events on the HC_knob were limited, the largest increase was found for peptide
+HC(44-64) from 0.5% up to 3.7% over the 4 weeks storage. Another relevant increase in
+deamidation was found on LC(73-113) from 2.3 to 4.1%.
+
+l In only one peptide, associated with the variable region, isomerization was observed. This in
+peptide HC(98-107): up to 2.5%.
+
+
+<figure>
+
+RIC
+
+<!-- PageFooter="biologics" -->
+
+</figure>
+
+
+<!-- PageNumber="17" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+P052_OA-02A10-GLLIAB4+LIAB11-His1_0-HIGG1-CH2-CH3-LALAPG-
+ABDEG-FJB_2024-01-26_001
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+### Results: AA sequence
+
+l AA sequence of GLLiab4+11_Heavy_Knob_LALAPG_ABDEG (MW (G0F): 50768.4
+Da)
+
+EVOLVESGGGLVQPGGSLRLSCAASGFTFSSYVMSWVRQAPGKGLEWVSHIQGGGITSYADSVKGRATISRDNSKNTLYLQ
+MNSLRAEDTAVYYCARWLVDYGLGNRGSMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV
+SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPS
+VFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
+KVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
+FLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPG
+
+l AA sequence of GLHis1_Light_CL1 (MW (pyroQ): 23646.4Da)
+
+QAVLTQPPSLSASPGASARLTCSLSSGTIVHGYHINWYQQKAGSPPRYLLRFYSDSNKHQGSGVPSRFSGSKDASANAGILLIS
+GLQPEDEADYYCGTYHSNTGTYVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVK
+AGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
+
+l AA sequence of CH2_CH3_Hole_LALAPG_ABDEG (MW (G0F) 26719.1 Da)
+
+DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
+VSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNG
+QPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPG
+
+
+<figure>
+</figure>
+
+
+RIC
+
+biologics
+
+
+<table>
+<tr>
+<td>Blue:</td>
+<td>VH and VL</td>
+</tr>
+<tr>
+<td>Green:</td>
+<td>N-glycosylation site 19</td>
+</tr>
+<tr>
+<td>Red:</td>
+<td>N-terminal cyclization</td>
+</tr>
+</table>
+
+
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+### Results: reduced RPLC-UV-MS
+
+l Overlays of the UV214nm profiles P052_OA-02A10-GLLiab4+Liab11-His1_0-
+hIgG1-CH2-CH3-LALAPG-ABDEG-FJB_2024-01-26_001
+
+
+<figure>
+
+×10 2
+
+DAD1 - A:Sig=214.0,8.0 Ref=360.0,100.0 P3016_Molecule2_W0_C8_19MAR2024.d
+
+HC_Knob
+
+6.5
+
+T0
+
+6
+
+T4w 37℃
+
+6
+
+x: Unknown fragment (13463 Da)
+
+0: GG clip (G144-G452)
+
+y: Intact LC without pyroQ
+
+1: GG clip (G55-G452)
+
+5.5
+
+Hole
+
+z: Intact LC (pyroQ) + LC fragments:
+
+2: unknown
+
+5
+
+b
+
+LC
+
+N terminal Q loss
+
+3: - 17 Da (potentially HC +
+succinimide)
+
+4.5
+
+a: Hydroxy-y-lactam oxidation
+
+C-terminal S loss
+
+z
+
+b: Intact Hole
+
+C-terminal CS loss
+
+4: Traces of Oxidation (+32 Da)
+
+4
+
+c: N-terminal DK loss
+
+5: Oxidation (+16Da)
+
+6: Intact HC_knob
+
+3.5
+
+7: PyroE
+
+3
+
+8: DP clip (E1-D276)
+
+2.5
+
+2
+
+1.5
+
+Unknown fragment*
+
+7
+
+1
+
+5
+
+c
+
+0.5
+
+x
+
+a
+
+y
+
+0
+
+3
+
+4
+
+1
+
+2
+
+8
+
+0
+
+2
+
+3
+
+4
+
+5
+
+6
+
+7
+
+8
+
+9
+
+10
+
+Response Units vs. Acquisition Time (min)
+
+11
+
+12
+
+13
+
+14
+
+15
+
+16
+
+17
+
+18
+
+19
+
+20
+
+21
+
+22
+
+23
+
+24
+
+Color legend:
+
+</figure>
+
+\* No MS data for this peak (falls outside the
+measurement window)
+
+Black: clear identity on RPLC-UV-MS
+
+Blue: modification with clear trend visible on RPLC-UV-MS
+Blue: modification in variable region also confirmed in peptide
+mapping
+
+Grey: most likely method induced modification
+
+
+<figure>
+</figure>
+
+
+RIC
+
+biologics
+
+<!-- PageNumber="20" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: reduced RPLC-UV-MS
+
+
+### l Deconvoluted spectra of Hole, LC and HC_Knob (peak b, peak z and peak 6)
+
+×10 6
+
++ESI Scan (rt: 9.2-10.2 min, 103 scans) Frag=200.0V P3016_Molecule2_W0_C8_19MAR2024.d Deconvoluted (Isotope Width=10.0)
+
+26717.00
+
+Theoretical mass Hole (G0F): 26719.1 Da
+
+1
+
+0.8
+
+0.6
+
+0.4
+
+0.2
+
+0
+
+21343.73
+
+32956.97
+
++ESI Scan (rt: 12.8-13.7 min, 91 scans) Frag=200.0V P3016_Molecule2_W0_C8_19MAR2024.d Deconvoluted (Isotope Width=10.0)
+
+x10 6
+
+1.5
+
+1.25
+
+1
+
+0.75
+
+0.5
+
+0.25
+
+0
+
+x10 5
+
+17938.20
+
+25795.40
+
+30285.87
+
+23644.57
+
+Theoretical mass LC (pyroQ): 23646.43 Da
+
++ESI Scan (rt: 16.5-21.2 min, 467 scans) Frag=200.0V P3016_Molecule2_W0_C8_19MAR2024.d Deconvoluted (Isotope Width=14.1)
+
+
+<figure>
+
+1
+
+Theoretical mass HC_knob (G0F): 50768.4 Da
+
+50764.08
+
+0.8
+
+0.6
+
+0.4
+
+0.2
+
+0
+
+43849.21
+
+53430.56
+
+58466.31
+
+10000
+
+12500
+
+15000
+
+17500
+
+20000
+
+22500
+00 25000 2750
+
+30000 32500 35
+35000 37500
+
+Counts vs. Deconvoluted Mass (amu)
+
+42500
+
+45000
+
+47500
+50000
+
+52500
+
+55000
+
+57500
+
+60000
+
+</figure>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="21" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l N-terminal and C-terminal modifications for HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w37℃</th>
+</tr>
+<tr>
+<td rowspan="2">EVOLVESGGGLVQPGGSLR</td>
+<td rowspan="2">HC(1-19)</td>
+<td></td>
+<td>98.6</td>
+<td>88.0</td>
+</tr>
+<tr>
+<td>PyroE</td>
+<td>1.4</td>
+<td>12.0</td>
+</tr>
+<tr>
+<td rowspan="3">QAVLTQPPSLSASPGASAR</td>
+<td rowspan="3">LC(1-19)</td>
+<td></td>
+<td>3.5</td>
+<td>0</td>
+</tr>
+<tr>
+<td>PyroQ</td>
+<td>96.5</td>
+<td>99.8</td>
+</tr>
+<tr>
+<td>N terminal Q loss</td>
+<td>0.0</td>
+<td>0.2</td>
+</tr>
+<tr>
+<td rowspan="3">TVAPTECS</td>
+<td rowspan="3">LC(216-223)</td>
+<td></td>
+<td>100.0</td>
+<td>99.6</td>
+</tr>
+<tr>
+<td>S loss</td>
+<td>0.0</td>
+<td>0.2</td>
+</tr>
+<tr>
+<td>CS loss</td>
+<td>0.0</td>
+<td>0.2</td>
+</tr>
+</table>
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="22" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l M/W oxidations in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w37℃</th>
+</tr>
+<tr>
+<td rowspan="2">LSCAASGFTFSSYVMSWVR</td>
+<td rowspan="2">HC(20-38)</td>
+<td></td>
+<td>97.1</td>
+<td>95.9</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>2.9</td>
+<td>4.1</td>
+</tr>
+<tr>
+<td rowspan="2">NTLYLQMNSLR</td>
+<td rowspan="2">HC(76-86)</td>
+<td></td>
+<td>98.4</td>
+<td>97.8</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>1.6</td>
+<td>2.2</td>
+</tr>
+<tr>
+<td rowspan="4">WLVDYGLGNR</td>
+<td rowspan="4">HC (098-107)</td>
+<td></td>
+<td>100.0</td>
+<td>93.2</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>0.0</td>
+<td>2.2</td>
+</tr>
+<tr>
+<td>Double oxidation</td>
+<td>0.0</td>
+<td>2.0</td>
+</tr>
+<tr>
+<td>+ 4 (Kynurenine)</td>
+<td>0.0</td>
+<td>2.7</td>
+</tr>
+<tr>
+<td rowspan="2">GSMDYWGQGTTVTVSSASTK</td>
+<td rowspan="2">HC(108-127)</td>
+<td></td>
+<td>97.1</td>
+<td>96.2</td>
+</tr>
+<tr>
+<td>Oxidation</td>
+<td>2.9</td>
+<td>3.8</td>
+</tr>
+</table>
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+biologics
+
+</figure>
+
+
+<!-- PageNumber="23" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l
+
+
+#### N/Q deamidation in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w 37℃</th>
+</tr>
+<tr>
+<td rowspan="2">GLEWVSHIQGGGITSYADSVK</td>
+<td rowspan="2">HC(44-64)</td>
+<td></td>
+<td>99.4</td>
+<td>96.3</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>0.6</td>
+<td>3.7</td>
+</tr>
+<tr>
+<td rowspan="2">DNSKNTLYLQMNSLR*</td>
+<td rowspan="2">HC(72-86)</td>
+<td></td>
+<td>98.1</td>
+<td>98.5</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>1.9</td>
+<td>1.5</td>
+</tr>
+<tr>
+<td rowspan="2">NTLYLQMNSLR</td>
+<td rowspan="2">HC(76-86)</td>
+<td></td>
+<td>99.7</td>
+<td>99.0</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>0.3</td>
+<td>1.0</td>
+</tr>
+<tr>
+<td rowspan="2">WLVDYGLGNR</td>
+<td rowspan="2">HC(98-107)</td>
+<td></td>
+<td>99.8</td>
+<td>99.0</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>0.2</td>
+<td>1.0</td>
+</tr>
+<tr>
+<td rowspan="2">DASANAGILLISGLQPEDEADYYCGTYHSNT GTYVFGGGTK</td>
+<td rowspan="2">LC(73-113)</td>
+<td></td>
+<td>97.5</td>
+<td>95.4</td>
+</tr>
+<tr>
+<td>deamidation</td>
+<td>2.5</td>
+<td>4.6</td>
+</tr>
+</table>
+
+*The deamidation level on the misscleaved peptide was checked as the peptide DNSK has bad retention to have a reliable
+quantification. However, the misscleaved peptide has low abundance which can also lead to unreliable quantification of
+modifications
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+biologics
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+<!-- PageNumber="24" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l Isomerization events in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w 37℃</th>
+</tr>
+<tr>
+<td rowspan="2">WLVDYGLGNR</td>
+<td rowspan="2">HC(98-107)</td>
+<td></td>
+<td>99.5</td>
+<td>95.1</td>
+</tr>
+<tr>
+<td>isomerization</td>
+<td>0.5</td>
+<td>4.9</td>
+</tr>
+</table>
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+biologics
+
+<!-- PageNumber="25" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Results: tryptic peptide map
+
+
+### l Clipping events in variable parts of HC_Knob and LC
+
+
+<table>
+<tr>
+<th colspan="5">Relative quantification by EIC (%)</th>
+</tr>
+<tr>
+<th>AA Sequence</th>
+<th>Seq Loc</th>
+<th>Modification</th>
+<th>T0</th>
+<th>T4w 37℃</th>
+</tr>
+<tr>
+<td>GLEWVSHIQGGGITSYADSVK</td>
+<td>HC(44-64)</td>
+<td></td>
+<td>100.0</td>
+<td>99.7</td>
+</tr>
+<tr>
+<td>GLEWVSHIQGG</td>
+<td>HC(44-54)</td>
+<td rowspan="2">GG clip</td>
+<td>0.0</td>
+<td>0.3*</td>
+</tr>
+<tr>
+<td>GITSYADSVK</td>
+<td>HC(55-64)</td>
+<td>0.0</td>
+<td>0.8*</td>
+</tr>
+</table>
+
+*Due to differences in ionization efficiency between small and large peptides, the level of clipping reported here is most
+likely an overestimation.
+
+
+For information purposes the following color code is applied: Values showing an increase or decrease by
+between 1.0% to 10.0% compared to T0 sample are in blue and underlined, whereas values showing an
+increase of more than 10.0% compared to T0 are in red, bold and underlined.
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="26" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+## Conclusions
+
+l A potential unidentified clipping event may be present. Two peaks were present in the RPLC-UV-
+MS profile for which no identity was found. One peak (RT around 12 min) had a clear mass of
+13463 Da, while no mass could be retrieved for the second peak (RT around 3 min). Further
+experiments are required to find the origin of the unknown peaks.
+A less abundant clipping was found between G143G14 which falls just outside the variable region of
+HC_Knob but for sure may impact the functionality. Another clipping, this time in the variable
+region, was found between G54G55 . This clipping was confirmed via peptide mapping in the
+stressed sample in low amounts: < 1%.
+
+l Cyclization of the N-terminal glutamate on the HC_knob increased up to 12.0% during temperature
+stress (both present in RPLC-UV-MS and peptide map). Cyclization of the N-terminus on the LC
+reached completion after storage for four weeks at 37℃.
+
+l In addition, tryptic peptide peaks containing oxidation were found in the variable regions.
+Especially for Wgg located on the HC_knob where the oxidation levels increased up to 6.9% after
+four weeks storage at 37℃. A second relevant increase in oxidation levels during the 4 weeks
+storage was found for HC(20-38): from 2.9 to 4.1%.
+
+l Deamidation events on the HC_knob were limited, the largest increase was found for peptide
+HC(44-64) from 0.6% up to 3.7% over the 4 weeks storage. Another relevant increase in
+deamidation was found on LC(73-113) from 2.5 to 4.6%.
+
+l In only one peptide, associated with the variable region, isomerization was observed. This in
+peptide HC(98-107): up to 4.9%.
+
+
+<figure>
+
+RIC
+
+<!-- PageFooter="biologics" -->
+
+</figure>
+
+
+<!-- PageNumber="27" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+### Signature section RIC
+
+
+#### Author
+
+
+<table>
+<tr>
+<th>Nathan Cardon</th>
+<th>Date:</th>
+<th>14-MAY-2024</th>
+</tr>
+<tr>
+<td>Sr Research Associate | Project Responsible</td>
+<td>Signature:</td>
+<td></td>
+</tr>
+<tr>
+<td colspan="3">Reviewer</td>
+</tr>
+<tr>
+<td>Gianni Vandenborre Ph.D.</td>
+<td>Date:</td>
+<td>14-MAY-2024</td>
+</tr>
+<tr>
+<td>Sr Scientist</td>
+<td>Signature:</td>
+<td></td>
+</tr>
+<tr>
+<td>Mabelle Meersseman</td>
+<td>Date:</td>
+<td>15-MAY-2024</td>
+</tr>
+<tr>
+<td>Group Leader</td>
+<td>Signature:</td>
+<td></td>
+</tr>
+<tr>
+<td colspan="3">Approver</td>
+</tr>
+<tr>
+<td>Koen Sandra Ph.D.</td>
+<td>Date:</td>
+<td>15-MAY-2024</td>
+</tr>
+<tr>
+<td>CEO</td>
+<td>Signature:</td>
+<td>Koen Sandra</td>
+</tr>
+</table>
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="28" -->
+<!-- PageBreak -->
+
+
+<figure>
+</figure>
+
+
+# Version control
+
+
+<table>
+<tr>
+<th>Version</th>
+<th>Date of issue</th>
+<th>Reason for version update</th>
+</tr>
+<tr>
+<td>01</td>
+<td>15-MAY-2024</td>
+<td>First issue</td>
+</tr>
+<tr>
+<td></td>
+<td></td>
+<td></td>
+</tr>
+<tr>
+<td></td>
+<td></td>
+<td></td>
+</tr>
+</table>
+
+
+15-MAY-2024
+
+Obo Jaussens
+
+
+<figure>
+
+RIC
+
+</figure>
+
+
+<!-- PageFooter="biologics" -->
+<!-- PageNumber="29" -->
+<!-- PageBreak -->
+
+
+<figure>
+
+RIC
+
+biologics
+
+</figure>
+
+
+YOUR MOLECULE. OUR ANALYTICS. NO SECRETS.
+
+<!-- PageFooter="www.RIC-biologics.com" -->

src/agents/field_mapper_agent.py

@@ -299,56 +299,15 @@ class FieldMapperAgent(BaseAgent):
         
         self.logger.info(f"Processing field: {field}")
         self.logger.info(f"Using document context: {ctx['document_context']}")
-        
-        # Split text into pages using the same markers as IndexAgent
-        page_markers = [
-            '<!-- PageBreak -->',
-            'Page',
-            '---',
-            '\n\n',  # Double newline as fallback
-        ]
-        
-        # First try to find which marker is used
-        used_marker = None
-        for marker in page_markers:
-            if marker in text:
-                used_marker = marker
-                self.logger.info(f"Found page marker: {marker}")
-                break
-        
-        if not used_marker:
-            self.logger.warning("No page markers found, falling back to double newline")
-            used_marker = '\n\n'
-        
-        # Split the text
-        if used_marker == '\n\n':
-            pages = [p.strip() for p in text.split(used_marker) if p.strip()]
-        else:
-            pages = []
-            current_page = []
-            
-            for line in text.split('\n'):
-                if used_marker in line:
-                    if current_page:
-                        pages.append('\n'.join(current_page))
-                    current_page = [line]
-                else:
-                    current_page.append(line)
-            
-            if current_page:
-                pages.append('\n'.join(current_page))
-        
-        self.logger.info(f"Split document into {len(pages)} pages")
-        
-        # Process each page
-        for i, page in enumerate(pages, 1):
-            self.logger.info(f"Processing page {i}/{len(pages)}")
-            value = self._extract_field_value_from_page(field, page, ctx["document_context"])
-            if value:
-                return value
-        
-        # If no value found in any page, try the search-based approach as fallback
-        self.logger.warning("No value found in page-by-page analysis, falling back to search-based approach")
+
+        # Process entire document at once
+        self.logger.info("Processing entire document...")
+        value = self._extract_field_value_from_page(field, text, ctx["document_context"])
+        if value:
+            return value
+        
+        # If no value found, try the search-based approach as fallback
+        self.logger.warning("No value found in document analysis, falling back to search-based approach")
         
         if index and "embeddings" in index:
             self.logger.info("Using semantic search with embeddings")

src/services/azure_di_service.py

@@ -1,6 +1,8 @@
 """Real wrapper goes here – currently not used by stub agents."""
 import logging
 import json
+from datetime import datetime
+from pathlib import Path
 from azure.ai.documentintelligence import DocumentIntelligenceClient
 from azure.ai.documentintelligence.models import DocumentContentFormat
 from azure.core.credentials import AzureKeyCredential
@@ -10,6 +12,8 @@ class AzureDIService:
     def __init__(self, endpoint: str, key: str):
         self.client = DocumentIntelligenceClient(endpoint=endpoint, credential=AzureKeyCredential(key))
         self.logger = logging.getLogger(__name__)
+        self.log_dir = Path("logs/di_content")
+        self.log_dir.mkdir(parents=True, exist_ok=True)
 
     def extract_tables(self, pdf_bytes: bytes):
         try:
@@ -35,6 +39,13 @@ class AzureDIService:
             if hasattr(result, "content"):
                 self.logger.info(f"Content type: {type(result.content)}")
                 self.logger.info(f"Content preview: {result.content[:500]}")
+                
+                # Save content to timestamped file
+                timestamp = datetime.now().strftime("%Y%m%d_%H%M%S")
+                log_file = self.log_dir / f"di_content_{timestamp}.txt"
+                with open(log_file, "w", encoding="utf-8") as f:
+                    f.write(result.content)
+                self.logger.info(f"Saved DI content to {log_file}")
             
             # Check if tables exist and log their structure
             if hasattr(result, "tables"):