Anti-phosphocholine antibodies and methods of their use.

Abstract

The present disclosure provides polypeptides that specifically bind to phosphocholine (PC). Also provided are pharmaceutical compositions comprising these polypeptides, nucleic acids encoding these polypeptides, expression vectors and host cells for making these polypeptides, and methods of treating a subject using these polypeptides.

Description

1 / 170 “ANTI-PHOSPHOCHOLINE ANTIBODIES AND METHODS OF USE THEREOF” CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to Application for U.S. Provisional Patent Serial No. 63 / 452,798, filed March 17, 2023, the full disclosure of which is incorporated herein by reference. REFERENCE TO THE LISTING OF SEQUENCES

[0002] This request contains a sequence listing that was submitted electronically in ST. 26 format and is incorporated herein by reference in its entirety. The ST. 26 copy, created on March 15, 2024, is named “208485_seqlist.xml” and is 644,762 bytes in size. FIELD

[0003] This disclosure relates to specific antibodies for phosphocholine (PC) and methods of using them. BACKGROUND

[0004] Phospholipids containing polyunsaturated fatty acids are highly susceptible to modification by reactive oxygen species (ROS) and non-radical oxidizing agents. Oxidized lipids in cell membranes and circulation can have both beneficial and detrimental effects on the human body. Endogenous oxidized phospholipids (OxPL) have been shown to function as stress signals, causing phagocytes, such as macrophages, to respond by triggering inflammatory programs and eliminating the stress source. However, excessive amounts of oxidized phospholipid products have been associated with chronic inflammation and the pathogenesis of various cardiopulmonary disorders, such as atherosclerosis and thrombosis, acute lung injury, and neurodegenerative processes.

[0005] Oxidized low-density lipoprotein (OxLDL) contains several OxPL species and is found in atherosclerotic lesions and detected in high concentrations in the serum of patients with hyperlipidemia, diabetes mellitus, and liver disease. The major phosphocholine (PC) group of OxPLs has been shown to be important for the binding of phospholipids to integral proteins of Petition 870250103709, dated 12 / 11 / 2025, page 9 / 179 2 / 170 membrane, such as CD36 and C-reactive protein (CRP), an innate defense molecule (Boullier et al., J Lipid Res. May 2005; 46(5): 969-76; Gershov et al., J Exp Med. November 6, 2000; 192(9): 1353-64).

[0006] Therefore, there is a need for therapies, including antibodies, that bind to PC to target OxPL in a wide range of diseases. SUMMARY

[0007] This disclosure provides polypeptides (e.g., antibodies) that specifically bind to PC. Pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for producing these antibodies, and methods for treating a subject using these antibodies are also provided. The polypeptides provided in this document are particularly advantageous because they bind to PC with high affinity, exhibit favorable stability, stress resistance and immunogenicity profiles, and can be produced in high yield. The polypeptides presented here are particularly useful for treating an inflammatory disorder or a degenerative disease in an individual.

[0008] Thus, in one aspect, the present disclosure provides an antibody that specifically binds to phosphocholine (PC), the antibody comprising: a VH comprising the amino acid sequences CDRH1, CDRH2 and CDRH3 from any of the VH amino acid sequences presented in SEQ ID NOs: 1-180; and a VL comprising the amino acid sequences CDRL1, CDRL2 and CDRL3 from any of the VL amino acid sequences presented in SEQ ID NOs: 181-368.

[0009] In one embodiment, the antibody comprises the amino acid sequences CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the amino acid sequences VH and VL, respectively, presented in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; 8 and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; 16 and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; 21 and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 Petition 870250103709, dated 12 / 11 / 2025, page 10 / 179 3 / 170 and 212; 31 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; 35 and 184; 36 and 184; 35 and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; 9 and 224; 40 and 184; 41 and 225; 8 and 226; 42 and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8 and 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243; 54 and 184; 55 and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248; 60 and 249; 8 and 250; 61 and 184; 35 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; 35 and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265; 76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; and 271; 84 and 272; 1 and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; and 269; 88 and 280; 89 and 269; 60 and 281; 90 and 269; 91 and 282; 22 and 283; 92 and 269;93 and 284; 94 and 285; 95 and 286; 96 and 269; 73 and 287; 97 and 288; 68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; 4 and 289; 101 and 284; 66 and 289; 89 and 293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; 66 and 269; 108 and 299; 109 and 300; 110 and 301; 111 and 302; 112 and 269; 113 and 303; 1 and 304; 72 and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309; 119 and 310; 120 and 311; 121 and 269; 122 and 312; 123 and 289; 9 and 313; 124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317; 127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324; 132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330; 138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 and 333; 143 and 334; 144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 e354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 e363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368.

[0010] In one embodiment, the antibody comprises the amino acid sequences CDRH1, CDRH2, and CDRH3, respectively, presented in the SEQ ID NOs: 369, 428, and 484; 370, 429, and 485; 371, 428, and 486; 372, Petition 870250103709, dated 12 / 11 / 2025, page 11 / 179 4 / 170 428 and 484; 373, 429 and 484; 374, 430 and 484; 375, 428 and 487; 376, 428 and 484; 377, 428 and 484; 378, 428 and 484; 379, 428 and 484; 372, 428 and 488; 376, 431 and 484; 380, 432e 484; 372, 428 and 489; 381,428 and 490; 382, 428 and 484; 381,428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381, 428e 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484; 393, 428 and 498; 376, 428 and 495; 369, 440 and 484; 397, 428 and 484; 389, 447 and 484; 398, 448 and 492; 373, 449e 490; 399, 428 and 484; 400, 450 and 484; 401, 428 and 484; 390, 428 and 484; 400, 428 and 499; 384, 429 and 484; 402, 436 and 484; 381, 451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and 500; 376, 452 and 501; 407, 428 and 484; 375, 428e 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489; 374, 434 and 484; 411, 460 and 505; 383, 428e 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484; 413, 459 and 484; 369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484; 369, 452 and 509; 388, 468 and 490; 377, 440e 484; 370, 428 and 484; 384, 467 and 487; 392, 469 and 510; 378, 464 and 484; 416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381, 428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484; 370, 428 and 514; 369, 475 and 484; 421, 436e 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, ​​434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520; 417, 460 and Petition 870250103709, dated 12 / 11 / 2025, page 12 / 179 5 / 170 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484; 384, 428 and 489;426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or 400, 452 and 484.

[0011] In one embodiment, the antibody comprises the amino acid sequences CDRL1, CDRL2, and CDRL3, respectively, presented in the SEQ ID NOs: 523, 591, and 656; 523, 592, and 657; 523, 593, and 658; 523, 591, and 659; 523, 594, and 659; 523, 595, and 660; 523, 596, and 659; 524, 591, and 659; 523, 591, and 661; 523, 591, and 662; 523, 597, and 658; 523, 598, and 662; 525, 599, and 659; 523, 600 and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531, 591 and 663; 523, 608 and 661; 523, 610 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659; 534, 619 and 662; 535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659; 523, 617 and 659; 523, 623 and 659; 538, 607 and 672; 523, 616 and 671;523, 624 and 659; 523, 620 and 659; 523, 625 and 660; 523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661; 523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676; 555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 and 659; 523, 592 and 670; 560, 591 and 667; 530, 591 and 659; 561, 603 and 666; 562, 591 and 659; 523, 616 and 660; 523, 602 and 677; 523, 616 and 659; 523, 630 and 660;563, 591 and 659; 523, 640 and 659; 564, 591 and 659; 523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; Petition 870250103709, dated 12 / 11 / 2025, page 13 / 179 6 / 170 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571,630 and 663; 572, 591 and 664; 573, 591 and 670; 523, 646 and 659; 574, 591 and 670; 523, 647 and 667; 575, 591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660; 527, 591 and 659; 581, 595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659; 560, 591 and 659; 580, 606 and 659; 589, 593 and 661; 523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672; 523, 626 and 668; 523, 655 and 659; or 523, 606 and 680.

[0012] In one embodiment, the antibody comprises the amino acid sequences CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3, presented in the SEQ ID NOs: 369, 428, 484, 523, 591 and 656; 370, 429, 485, 523, 592 and 657; 371, 428, 486, 523, 593 and 658; 372, 428, 484, 523, 591 and 659; 373, 429, 484, 523, 594 and 659; 369, 428, 484, 523, 591 and 659; 374, 430, 484, 523, 591 and 659; 369, 428, 484, 523, 595 and 660; 375, 428, 487, 523, 596 and 659; 376, 428, 484, 524, 591 and 659; 377, 428, 484, 523, 591 and 661; 378, 428, 484, 523, 591 and 662; 372, 428, 484, 523, 597 and 658; 379, 428, 484, 523, 598 and 662; 372, 428, 488, 525, 599 and 659; 376, 431, 484, 523, 600 and 663; 380, 432, 484, 523, 591 and 664; 372, 428, 489, 523, 601 and 659; 381, 428, 490, 523, 591 and 659; 382, 428, 484, 526, 597 and 665; 381, 428, 491, 523, 602 and 659; 369, 428, 484, 527, 591 and 661; 377, 428, 492, 528, 591 and 662; 376, 433, 484, 529, 603 and 662; 383, 434, 484, 523, 604 and 666; 383, 428, 484, 523, 605 and 667; 384, 435, 484, 530, 606 and 659; 369, 436, 484, 523, 607 and 659; 372, 437, 487, 523, 591 and 659; 372, 428, 484, 523, 608 and 659; 385, 428, 493, 523, 609 and 662; 386, 428, 484, 531, 591 and 663; 372, 437, 484, 523, 608 and 661; 377, 428, 484, 523, 610 and 659; 387, 428, 484, 523, 611 and 668; 385, 428, 484, 523, 611 and 658; 372, 438, 484, 523, 596 and 662; 388, 428, 494, 523, 612 and 667; 369, 439, 484, 523, 613 and 668; 389, 428, 484, 523, 591 and 669; 382, 428, 484, 523, 591 and 663; 369, 428, 484, 523, 614 and 659; 381, 428, 484, 523, 591 and 659; 376, 440, 495, 523, 591 and 659; 381, 428, 484, Petition 870250103709, dated 12 / 11 / 2025, page 14 / 179 7 / 170 532, 615 and 662; 381, 428, 484, 523, 616 and 670; 390, 441,484, 523, 591 and 659; 370, 442, 484, 523, 591 and 668; 391, 428, 484, 523, 617 and 671; 377, 428, 484, 533, 595 and 659; 377, 428, 484, 523, 618 and 659; 392, 432, 484, 523, 591 and 659; 377, 443, 484, 534, 619 and 662; 376, 428, 484, 535, 620 and 659; 393, 428, 484, 536, 621 and 659; 381, 428, 484, 537, 603 and 671; 383, 444, 489, 523, 622 and 59; 372, 428, 484, 523, 617 and 659; 377, 428, 484, 523, 623 and 659; 376, 428, 484, 538, 607 and 672; 369, 428,484, 523, 616 and 671; 376, 428, 484, 523, 624 and 659; 394, 428, 484, 523, 591 and 659; 369, 428, 484, 523, 620 and 659; 383, 444, 496, 523, 625 and 660; 385, 428, 484, 523, 602 and 671; 376, 434, 484, 523, 591 and 659; 395, 445, 497, 523, 611 and 663; 396, 446,487, 523, 626 and 670; 369, 428, 484, 523, 617 and 659; 392, 428, 484, 523, 591 and 662; 394, 428, 484, 523, 606 and 673; 393, 428, 498, 523, 591 and 659; 376, 428, 495, 523, 627 and 671; 369, 440, 484, 523, 628 and 671; 397, 428, 484, 539, 591 and 662; 389, 447,484, 523, 591 and 659; 398, 448, 492, 523, 591 and 670; 373, 449, 490, 523, 611 and 659; 399, 428, 484, 537, 613 and 671; 400, 450, 484, 540, 598 and 659; 401, 428, 484, 541, 591 and 659; 390, 428, 484, 542, 629 and 659; 376, 428, 484, 523, 591 and 671; 400, 428,499, 523, 591 and 659; 381, 428, 484, 523, 630 and 667; 384, 429, 484, 543, 631 and 659; 369, 428, 484, 523, 632 and 664; 402, 436, 484, 523, 597 and 661; 381, 451, 484, 523, 591 and 656; 403, 428, 484, 523, 633 and 659; 369, 429, 484, 544, 607 and 659; 404, 429,484, 523, 630 and 659; 372, 429, 484, 523, 602 and 659; 381, 428, 484, 523, 591 and 665; 388, 428, 484, 523, 610 and 674; 405, 451, 484, 523, 634 and 671; 406, 428, 484, 545, 591 and 661; 400, 428, 484, 523, 635 and 667; 404, 428, 484, 546, 591 and 659; 384, 432,500, 523, 636 and 664; 376, 452, 501, 547, 591 and 663; 407, 428, 484, 548, 619 and 659; 375, 428, 484, 523, 637 and 659; 372, 428, 484, 523, 607 and 659; 408, 428, 484, 523, 638 and 659; 386, 428, 484, 523, 591 and 659; 369, 428, 497, 523, 591 and 659; 403, 453,484, 549, 591 and 659; 402, 454, 484, 523, 591 and 659; 383, 428, 484, 523, 591 and 659; 383, 434, 500, 523, 591 and 659; 376, 455, 502, 550, 591 and 675; 383, 435, 484, 523, 591 and 664; 369, 428, 484, 523, 602 and 659; 376, 428, 484, 551, 591 and 659; 376, 428,484, 552, 591 and 659; 383, 428, 484, 553, 591 and 676; 376, 428, 484, 554, 591 and 659; 376, 428, 490, 523, 591 and 676; 369, 428, 503, 555, 606 and 659; 409, 428, 484, 523, 591 and 659; 383, 428, 504, 556, 591 and 659; 369, 434, 484, 523, 591 and 659; 390, 428,484, Petition 870250103709, dated 12 / 11 / 2025, page 15 / 179 8 / 170 523, 637 and 677; 369, 456, 484, 523, 428, 484, 558, 591 and 659; 404, 458, 677; 383, 459, 484, 553, 639 and 659; 523, 591 and 659; 404, 428, 484,559, 429, 484, 523, 606 and 659; 383,428, 659; 412, 455, 493, 523, 592 and 670; 523, 606 and 659; 383, 461, 484,523, 434, 484, 530, 591 and 659; 376,437, 659; 383, 428, 484, 562, 591 and 659; 523, 602 and 677; 400, 434, 506,549, 429, 484, 523, 591 and 659; 384,429, 659; 377, 465, 484, 523, 630 and 660; 523, 591 and 663; 414, 466, 484,523, 428, 489, 564, 591 and 659; 369,428, 677; 369, 428, 491, 565, 591 and662; 523, 591 and 659; 369, 452, 509,566, 452, 484, 523, 644 and 667; 377,440, 656; 384, 467, 487, 523, 591 and659; 523, 606 and 659; 377, 428, 484,569, 428, 484, 523, 606 and 659; 370,428, 663; 376, 428, 502, 572, 591 and664; 573, 591 and 670; 376, 428, 512,523, 428, 484, 523, 647 and 667; 381,428, 659; 404, 471, 484, 537, 591 and659; 576, 591 and 659; 419, 428, 484,577, 473, 484, 523, 591 and 664; 383,474, 663; 420, 434, 484, 523, 595 and 659; 523, 591 and 677; 383, 428, 484,523, 436, 484, 523, 649 and 664; 378,452, 659; 376, 428, 504, 523, 591 and 667; and 659; 370, 457, 484, 557, 591 and 659; 383, 523, 591 and 659; 410, 428, 484, 523, 591 and , 428, 489, 549, 591 and 667; 374, 434,484, and 666; 411, 460, 505, 523, 591 and 672; 372, 523, 591, and 659; 386, 460, 490, 523, 601, 428, 484, 560, 591, and 667; 372, 428, 484, and 677; 369, 429, 484, 523, 606, and 659; 369, 561, 603, and 666; 383, 462, 500, 523, 591, and , 463, 484, 523, 616, and 660; 376, 464,484, and 659; 369, 436, 507, 523, 591, and 659; 404, 523, 616, and 659; 369, 429, 484, 523, 591, and , 459, 484, 563, 591, and 659; 369, 452,484, and 659; 373, 428, 484, 523, 591, and 659; 415, 523, 591 and 671; 400, 428, 484, 523, 641 and , 458, 508, 523, 642 and 664; 392, 467,484, and 659; 388, 468, 490, 523, 591 and 659; 369, 567, 606 and 659; 370, 428, 484, 523, 591 and , 469, 510, 568, 591 and 659; 378, 464,484, and 659; 416, 434, 484, 523, 603 and 659; 370, 570, 628 and 678; 369, 452, 484, 571, 630 and , 428, 484, 523, 591 and 665; 392, 428,484, and 659; 377, 428, 484, 574, 591 and 670; 383, 575, 591 and 659; 383, 470, 501, 523, 591 and , 428, 484, 523, 635 and 670; 383, 472,513, and 659; 397, 428, 484, 523, 648 and 679; 372, 523, 592 and 659; 372, 428, 484, 523, 591 and , 428, 514, 523, 591 and 659; 369, 428,484, and 659; 369, 475, 484, 523, 591 and 659; 421, 523, 591 and 659; 376, 476, 515, 578, 641 and , 469, 484, 523, 606 and 660; 383, 461,484, Petition 870250103709, dated 12 / 11 / 2025, page 16 / 179 9 / 170 523, 616 and 659; 369, 428, 484, 523, 650 and 656; 369, 428, 516, 523, 591 and 659; 405, 460, 484, 523, 618 and 659; 413, 431,484, 523, 591 and 659; 382, ​​428, 484, 579, 621 and 671; 383, 428, 484, 523, 646 and 659; 372, 428, 484, 580, 591 and 660; 406, 429, 484, 527, 591 and 659; 383, 428, 517, 581, 595 and 659; 377, 437, 518, 582, 640 and 664; 369, 477, 487, 583, 651 and 659; 403, 464, 484, 534, 591 and 659; 383, 459, 484, 523, 606 and 659; 369, 454, 484, 584, 591 and 671; 372, 478, 519, 523, 591 and 680; 423, 429, 484, 523, 591 and 681; 383, 428, 484, 585, 591 and 659; 369, 434, 484, 557, 591 and 659; 382, 434, 484, 523, 649 and 659; 424, 479, 484, 523, 616 and 660; 376, 429, 484, 586, 591 and 666; 425, 428, 484, 523, 592 and 659; 369, 436, 484, 587, 652 and 659; 403, 428, 520, 588, 638 and 659; 417, 460, 484, 523, 591 and 659; 409, 460, 484, 523, 623 and 664; 404, 452, 484, 523, 591 and 659; 369, 428, 484, 523, 591 and 682; 383, 428, 521, 553, 653 and 659; 372, 480, 493, 523, 591 and 659; 369, 428, 484, 523, 654 and 659; 369, 477, 484, 523, 648 and 659; 369, 481, 484, 560, 591 and 659; 369, 452, 484, 523, 591 and 667; 409, 428, 484, 580, 606 and 659; 384, 452, 484, 589, 593 and 661; 377, 482, 484, 523, 591 and 659; 410, 483, 484, 523, 591 and 659; 384, 428, 489, 523, 591 and 659; 426, 429, 484, 523, 622 and 659; 376, 428, 484, 523, 637 and 676; 427, 428, 484, 523, 591 and 671; 373, 452, 506, 523, 591 and 659; 369, 428, 484, 590, 622 and 659; 369, 429, 521, 555, 591 and 661; 405, 428, 522, 523, 615 and 672; 376, 428, 510, 523, 591 and 659; 384, 428, 484, 523, 626 and 668; 410, 429, 484, 523, 591 and 659; 400, 452, 484, 523, 655 and 659; or 369, 434, 484, 523, 606 and 680.

[0013] In one embodiment, the antibody comprises the amino acid sequence VH of any of the SEQ ID NOs: 1-180.

[0014] In one embodiment, the antibody comprises the VL amino acid sequence of any of the SEQ ID NOs: 181-368.

[0015] In one embodiment, VH and VL comprise the amino acid sequences, respectively, presented in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; 8 and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; 16 and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; 21 and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 and 212; 31 Petition 870250103709, dated 12 / 11 / 2025, page 17 / 179 10 / 170 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; 35 and 184; 36 and 184; 35 and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; 9 and 224; 40 and 184; 41 and 225; 8 and 226; and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8 and 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243; 54 and 184; 55 and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248; 60 and 249; 8 and 250; 61 and 184; 35 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; 35 and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265; 76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; 83 and 271; 84 and 272; and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; 87 and 269; 88 and 280; and 269; 60 and 281; 90 and 269; 91 and 282; 22 and 283; 92 and 269; 93 and 284; 94 and 285;95 and 286; 96 and 269; 73 and 287; 97 and 288; 68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; and 289; 101 and 284; 66 and 289; 89 and 293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; 66 and 269; 108 and 299; 109 and 300; 110 and 301; 111 and 302; 112 and 269; 113 and 303; 1 and 304; 72 and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309; 119 and 310; 120 and 311; 121 and 269;122 and 312; 123 and 289; 9 and 313; 124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317;127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324;132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330;138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 and 333; 143 and 334;144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 and 354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 and 363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368.

[0016] In one embodiment, the antibody is a single-chain variable fragment (scFv).

[0017] In one embodiment, the antibody comprises a Petition 870250103709, dated 12 / 11 / 2025, page 18 / 179 11 / 170 constant heavy chain region, or an Fc region thereof, optionally selected from the group consisting of human IgGi, IgG2, IgG3, IgG4, IgAi and IgA2.

[0018] In one embodiment, the constant region of the heavy chain is a human IgGi.

[0019] In one embodiment, the constant region of the heavy chain is a human IgG4.

[0020] In one embodiment, the amino acid sequence of the constant region of the human IgG4 heavy chain comprises a P at position 228, numbered according to the EU numbering system.

[0021] In one embodiment, the constant region of the heavy chain is a variant of a wild-type constant region of the heavy chain, wherein the variant constant region of the heavy chain binds to an Fc gamma receptor (FcyR) with lower affinity than the wild-type constant region of the heavy chain binds to FcyR.

[0022] In one embodiment, the amino acid sequence of the constant region of the heavy chain comprises: A at position 234; A at position 235; A, Q or G at position 297; or A or G at position 329, in each case numbered according to the EU numbering system.

[0023] In one embodiment, the amino acid sequence of the constant region of the heavy chain comprises: A at positions 234 and 235; A at positions 234, 235 and 329; or A at positions 234, 235 and G at position 329, in each case numbered according to the EU numbering system.

[0024] In one embodiment, the constant region of the heavy chain is a variant of a wild-type constant region of the heavy chain, and the variant constant region of the heavy chain has a higher affinity for the human neonatal Fc receptor (FcRn) at pH 6 compared to the affinity of the wild-type constant region of the heavy chain for the human FcRn at pH 6.

[0025] In one embodiment, the amino acid sequence of the constant region of the heavy chain comprises: L and S at positions 428 and 434, respectively; K, F, and Y at positions 433, 434, and 436, respectively; or Y, T, and E Petition 870250103709, dated 12 / 11 / 2025, page 19 / 179 12 / 170 in positions 252, 254 and 256, respectively, in each case numbered according to the EU numbering system.

[0026] In one embodiment, the antibody comprises a constant region of the light chain, optionally a human kappa or lambda constant region.

[0027] In one aspect, the present disclosure provides a polypeptide comprising a VH comprising the amino acid sequences CDRH1, CDRH2 and CDRH3 of any of the VH amino acid sequences presented in SEQ ID NOs: 1-180.

[0028] In one embodiment, the polypeptide comprises the amino acid sequences CDRH1, CDRH2, and CDRH3, respectively, presented in the SEQ ID NOs: 369, 428, and 484; 370, 429, and 485; 371, 428, and 486; 372, 428, and 484; 373, 429, and 484; 374, 430, and 484; 375, 428, and 487; 376, 428, and 484; 377, 428, and 484; 378, 428, and 484; 379, 428, and 484; 372, 428, and 488; 376, 431, and 484; 380, 432 and 484; 372, 428 and 489; 381, 428 and 490; 382, 428 and 484; 381, 428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381, 428 and 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484; 393, 428 and 498; 376, 428 and 495; 369, 440 and 484; 397, 428 and 484;389, 447 and 484; 398, 448 and 492; 373, 449 and 490; 399, 428 and 484; 400, 450 and 484; 401, 428 and 484; 390, 428 and 484; 400, 428 and 499; 384, 429 and 484; 402, 436 and 484; 381, 451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and 500; 376, 452 and 501; 407, 428 and 484; 375, 428 and 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489; 374, 434 and 484; 411, 460 and 505; 383, 428 and; Petition 870250103709, dated 12 / 11 / 2025, page 20 / 179 13 / 170 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484; 413, 459 and 484; 369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484; 369, 452 and 509; 388, 468 and 490; 377, 440 and 484; 370, 428 and 484; 384, 467 and 487; 392, 469 and 510; 378, 464 and 484; 416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381, 428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484; 370, 428 and 514; 369, 475 and 484; 421, 436 and 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, ​​434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520;417, 460 and 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484; 384, 428 and 489; 426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or 400, 452 and 484.

[0029] In one embodiment, VH comprises the amino acid sequences CDRH1, CDRH2, and CDRH3, respectively, presented in the SEQ ID NOs: 369, 428, and 484; 370, 429, and 485; 371, 428, and 486; 372, 428, and 484; 373, 429, and 484; 374, 430, and 484; 375, 428, and 487; 376, 428, and 484; 377, 428, and 484; 378, 428, and 484; 379, 428, and 484; 372, 428, and 488; 376, 431, and 484; 380, 432 and 484; 372, 428 and 489; 381, 428 and 490; 382, 428 and 484; 381, 428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381, 428 and 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484; 393, 428 and 498; 376, 428 and 495; 369, 440 and 484; 397, 428 and 484; 389, 447 and 484;398, 448 and 492; 373, 449 and 490; 399, 428 and 484; 400, 450 and 484; 401,428 and 484; 390, 428 and 484; 400, 428 and 499; Petition 870250103709, dated 12 / 11 / 2025, page 21 / 179 14 / 170 384, 429 and 484; 402, 436 and 484; 381,451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and 500; 376, 452 and 501; 407, 428 and 484; 375, 428 and 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489; 374, 434 and 484; 411, 460 and 505; 383, 428 and 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484; 413, 459 and 484; 369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484; 369, 452 and 509; 388, 468 and 490; 377, 440 and 484; 370, 428 and 484; 384, 467 and 487; 392, 469 and 510; 378, 464 and 484;416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381, 428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484; 370, 428 and 514; 369, 475 and 484; 421, 436 and 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, 434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520; 417, 460 and 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484; 384, 428 and 489; 426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or 400, 452 and 484.

[0030] In one embodiment, VH comprises any of the amino acid sequences presented in SEQ ID NOs: 1-180.

[0031] In one aspect, the present disclosure provides a polypeptide comprising a VL comprising the amino acid sequences CDRL1, CDRL2 and CDRL3 of any of the VL amino acid sequences set forth in SEQ ID Nos: 181-368.

[0032] In one embodiment, the polypeptide comprises the Petition 870250103709, dated 12 / 11 / 2025, p. 22 / 179 15 / 170 amino acid sequences CDRL1, CDRL2, and CDRL3, respectively, established in the SEQ ID NOs: 523, 591, and 656; 523, 592, and 657; 523, 593, and 658; 523, 591, and 659; 523, 594, and 659; 523, 595, and 660; 523, 596, and 659; 524, 591, and 659; 523, 591, and 661; 523, 591, and 662; 523, 597, and 658; 523, 598, and 662; 525, 599, and 659; 523, 600, and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531, 591 and 663; 523, 608 and 661; 523, 610 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659; 534, 619 and 662; 535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659; 523, 617 and 659; 523, 623 and 659; 538, 607 and 672; 523, 616 and 671; 523, 624 and 659; 523, 620 and 659; 523, 625 and 660;523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661; 523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676; 555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 and 659; 523, 592 and 670; 560, 591 and 667; 530, 591 and 659; 561, 603 and 666; 562, 591 and 659; 523, 616 and 660; 523, 602 and 677; 523, 616 and 659; 523, 630 and 660; 563, 591 and 659; 523, 640 and 659; 564, 591 and 659;523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571, 630 and 663;572, 591 and 664; 573, 591 and 670; 523, 646 and 659; 574, 591 and 670; 523, 647 and 667; 575,591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660;527, Petition 870250103709, dated 12 / 11 / 2025, page 23 / 179 16 / 170 591 and 659; 581,595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659; 560, 591 and 659; 580, 606 and 659; 589, 593 and 661; 523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672; 523, 626 and 668; 523, 655 and 659; or 523, 606 and 680.

[0033] In one embodiment, the VL comprises the amino acid sequences CDRL1, CDRL2, and CDRL3, respectively, established in the SEQ ID NOs: 523, 591, and 656; 523, 592, and 657; 523, 593, and 658; 523, 591 and 659; 523, 594 and 659; 523, 595 and 660; 523, 596 and 659; 524, 591 and 659; 523, 591 and 661; 523, 591 and 662; 523, 597 and 658; 523, 598 and 662; 525, 599 and 659; 523, 600 and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531, 591 and 663; 523, 608 and 661; 523, 610 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659; 534, 619 and 662; 535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659; 523, 617 and 659; 523, 623 and 659; 538, 607 and 672; 523, 616 and 671; 523, 624 and 659; 523, 620 and 659; 523, 625 and 660; 523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661; 523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676; 555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 and 659; 523, 592 and 670; 560, 591 and 667; 530, 591 and 659; 561, 603 and 666; 562, 591 and 659; 523, 616 and 660; 523, 602 and 677; 523, 616 Petition 870250103709, dated 12 / 11 / 2025, page 24 / 179 17 / 170 and 659; 523, 630 and 660; 563, 591 and 659; 523, 640 and 659; 564, 591 and 659; 523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571,630 and 663; 572, 591 and 664; 573, 591 and 670; 523, 646 and 659; 574, 591 and 670; 523, 647 and 667; 575, 591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660; 527, 591 and 659; 581, 595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659; 560, 591 and 659; 580, 606 and 659; 589, 593 and 661; 523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672;523, 626 and 668; 523, 655 and 659; or 523, 606 and 680.

[0034] In one embodiment, VL comprises any of the amino acid sequences set forth in SEQ ID NOs: 181-368.

[0035] In one embodiment, an antibody or polypeptide disclosed herein is conjugated to a cytotoxic agent, cytostatic agent, toxin, radionuclide, or detectable marker.

[0036] In one aspect, the present disclosure provides a polynucleotide encoding a VH and / or a VL of an antibody disclosed herein, or a polypeptide disclosed herein.

[0037] In one aspect, the present disclosure provides a vector comprising the polynucleotide disclosed herein.

[0038] In one embodiment, the vector is an adeno-associated virus (AAV) vector.

[0039] In one aspect, the present disclosure provides a recombinant host cell comprising:

[0040] (a) a polynucleotide disclosed here;

[0041] (b) a vector disclosed here;

[0042] (c) a first polynucleotide that codes for a Petition 870250103709, dated 12 / 11 / 2025, page 25 / 179 18 / 170 VH or heavy chain of an antibody disclosed in this document and a second polynucleotide encoding a VL or light chain of an antibody disclosed in this document; or

[0043] (d) a first vector comprising a first polynucleotide encoding a VH or heavy chain of an antibody disclosed herein, and a second vector comprising a second polynucleotide encoding a VL or light chain of an antibody disclosed herein.

[0044] In one aspect, the present disclosure provides a pharmaceutical composition comprising an antibody or polypeptide disclosed herein, a polynucleotide disclosed herein, a vector disclosed herein or a host cell disclosed herein and a pharmaceutically acceptable carrier or excipient.

[0045] In one aspect, the present disclosure provides a method for producing an antibody or polypeptide, the method comprising cultivating a host cell disclosed herein under suitable conditions, such that the polynucleotide is expressed and the antibody or polypeptide is produced.

[0046] In one aspect, the present disclosure provides a method for inhibiting PC activity in a subject, the method comprising administering to the subject an effective amount of an antibody or polypeptide disclosed herein, a polynucleotide disclosed herein, a vector disclosed herein, a host cell disclosed herein or a pharmaceutical composition disclosed herein.

[0047] In one aspect, the present disclosure provides a method of treating an inflammatory disorder or degenerative disease in a subject, the method comprising administering to the subject an effective amount of an antibody or polypeptide disclosed herein, a polynucleotide disclosed herein, a vector disclosed herein, a host cell disclosed herein or a pharmaceutical composition disclosed herein.

[0048] In one aspect, the present disclosure provides the use of an antibody or polypeptide disclosed herein, a polynucleotide disclosed herein, a vector disclosed herein, a host cell disclosed herein or a pharmaceutical composition disclosed herein, for the manufacture of a medicament for Petition 870250103709, dated 12 / 11 / 2025, page 26 / 179 19 / 170 the treatment of an inflammatory disorder or degenerative disease in a subject who needs it.

[0049] In one aspect, the present disclosure provides an antibody or polypeptide disclosed herein, a polynucleotide disclosed herein, a vector disclosed herein, a host cell disclosed herein or a pharmaceutical composition disclosed herein, for use in medicine.

[0050] In one aspect, the present disclosure provides an antibody or polypeptide disclosed herein, a polynucleotide disclosed herein, a vector disclosed herein, a host cell disclosed herein, or a pharmaceutical composition disclosed herein, for use in the treatment of an inflammatory disorder or degenerative disease in a subject in need thereof.

[0051] In one embodiment, the inflammatory disorder or degenerative disease is selected from the group consisting of organ reperfusion injury, such as myocardial infarction-induced reperfusion injury, Kawasaki disease, non-alcoholic steatohepatitis (NASH), organ transplant rejection, atherosclerosis, type 1 or type 2 diabetes, rheumatoid arthritis, osteoporosis, acute lung injury, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pain, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), stroke, Huntington's disease, frontotemporal dementia (FTD), multiple sclerosis (MS), isolated demyelinating diseases of the central nervous system, osteoarthritis, Crohn's disease, and ulcerative colitis. DETAILED DESCRIPTION

[0052] This disclosure provides polypeptides (e.g., antibodies) that bind specifically to PC. Pharmaceutical compositions comprising these polypeptides, nucleic acids encoding these polypeptides, expression vectors and host cells for the production of these polypeptides, and methods for treating an individual using these polypeptides are also provided. The polypeptides provided in this document are particularly advantageous because they bind to PC with high affinity, exhibit Petition 870250103709, dated 12 / 11 / 2025, page 27 / 179 20 / 170 favorable stability, stress resistance, and immunogenicity profiles, and can be produced in high yield. The polypeptides presented here are particularly useful for treating an inflammatory disorder or a degenerative disease in an individual. DEFINITIONS

[0053] As used in this document, the terms “antibody” and “antibodies” include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules comprising antibody CDRs, VH regions, and / or VL regions. Examples of antibodies include, without limitation, monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain molecules and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody heavy chain dimer, an antibody light chain-antibody heavy chain pair, intrabodies, heteroconjugated antibodies, antibody-drug conjugates,Single-domain antibodies, monovalent antibodies, single-chain antibodies or single-chain Fvs (scFv), camelized antibodies, affibodies, Fab fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies (including, for example, anti-anti-Id antibodies), and antigen-binding fragments of any of the above. In certain embodiments, the antibodies described in this document refer to polyclonal antibody populations. Antibodies may be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), of any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or of any subclass (e.g., IgG2a or IgG2b) of the immunoglobulin molecule. In certain embodiments, the antibodies described in this document are IgG antibodies, or a class (e.g., human IgG1 or IgG4) or subclass thereof. In one specific embodiment, the antibody is a humanized monoclonal antibody. In another embodiment, Petition 870250103709, dated 12 / 11 / 2025, p. 28 / 179 21 / 170 specifically, the antibody is a human monoclonal antibody.

[0054] “Multispecific antibodies” are antibodies (e.g., bispecific antibodies) that bind specifically to two or more different antigens or to two or more different regions of the same antigen. Multispecific antibodies include bispecific antibodies that contain two different antigen-binding sites (unique to the Fc region). Multispecific antibodies may include, for example, recombinantly produced antibodies, human antibodies, humanized antibodies, resurfaced antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, heteroconjugated antibodies, single-linked single-chain antibodies or single-linked Fvs (scFv), camelized antibodies, affibodies, linked Fab fragments, F(ab')2 fragments, chemically linked Fvs, and disulfide-linked Fvs (sdFv).Multispecific antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), of any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclass (e.g., IgG2a or IgG2b) of the immunoglobulin molecule. In certain embodiments, the multispecific antibodies described in this document are IgG antibodies, or a class (e.g., human IgG1, IgG2, or IgG4) or subclass thereof.

[0055] As used in this document, the term “CDR” or “complementarity-determining region” means the non-contiguous antigen-binding sites found in the variable regions of heavy and light chain polypeptides. These specific regions have been described, for example, by Kabat et al., J. Biol. Chem. 252, 6609 to 6616 (1977) and Kabat et al., Sequences of protein of immunological interest. (1991), by Chothia et al., J. Mol. Biol. 196:901-917 (1987), and by MacCallum et al., J. Mol. Biol. 262:732 to 745 (1996), all of which are incorporated herein by reference in their entirety, where the definitions include overlapping or subsets of amino acid residues when compared to each other. In certain modalities, the term “CDR” refers to a CDR as defined by MacCallum et al., J. Mol. Biol. 262:732-745 (1996) and Martin A. “Protein Sequence Petition 870250103709, dated 12 / 11 / 2025, page 29 / 179 22 / 170 and Structure Analysis of Antibody Variable Domains,” in Antibody Engineering, Kontermann and Dübel, eds., Chapter 31, pp. 422-439, Springer-Verlag, Berlin (2001). In certain embodiments, the term “CDR” is a CDR as defined by Kabat et al., J. Biol. Chem. 252, 6609 to 6616 (1977) and Kabat et al., Sequences of protein of immunological interest. (1991). In certain embodiments, heavy chain CDRs and light chain CDRs of an antibody are defined using different conventions. In certain embodiments, heavy chain CDRs and / or light chain CDRs are defined by performing structural analysis of an antibody and identifying residues in the variable region(s) predicted to make contact with an epitope region of a target molecule (e.g., PC). CDRH1, CDRH2, and CDRH3 denote the CDRs of the heavy chain, and CDRL1, CDRL2, and CDRL3 denote the CDRs of the light chain.

[0056] As used in this document, the terms “variable region” and “variable domain” are used interchangeably and are common in the art. The variable region typically refers to a portion of an antibody, usually a portion of a light or heavy chain, typically about 110 to 120 amino acids from the amino terminal or 110 to 125 amino acids in the mature heavy chain and about 90 to 115 amino acids in the mature light chain, which differ extensively in sequence between antibodies and are used in the binding and specificity of a specific antibody to its specific antigen. Variability in sequence is concentrated in regions called complementarity-determining regions (CDRs), while the most highly conserved regions in the variable region are called structural regions (FRs).Without intending to be limited by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the antibody's interaction and specificity with the antigen. In certain embodiments, the variable region is a human variable region. In certain embodiments, the variable region comprises rodent or murine CDRs and human structure regions (FRs). In certain embodiments, the variable region comprises rodent or murine CDRs and primate structure regions (FRs) (e.g., non-human primates). Petition 870250103709, dated 12 / 11 / 2025, page 30 / 179 23 / 170

[0057] As used herein, the terms “VH” and “VL” refer to antibody heavy and light chain variable regions, respectively, as described in Kabat et al., (1991) Sequences of Proteins of Immunological Interest (NIH Publication No. 91-3242, Bethesda), which is incorporated herein by reference in its entirety.

[0058] As used in this document, the term “constant region” is common in the art. The constant region is a portion of an antibody, for example, a carboxyl terminal portion of a light and / or heavy chain, that is not directly involved in the binding of an antibody to an antigen, but which may exhibit various effector functions, such as interaction with an Fc receptor (e.g., Fc gamma receptor).

[0059] As used in this document, the term “heavy chain” when used in reference to an antibody may refer to any distinct type, for example, alpha (α), delta (δ), epsilon (ε), gamma (γ) and mu (μ), based on the amino acid sequence of the constant region, which give rise to the antibody classes IgA, IgD, IgE, IgG and IgM, respectively, including IgG subclasses, for example, IgGi, IgG2, IgG3 and IgG4.

[0060] As used in this document, the term “light chain” when used in reference to an antibody may refer to any distinct type, for example, kappa (κ) or lambda (λ), based on the amino acid sequence of the constant region. The amino acid sequences of the light chain are well known in the art. In specific embodiments, the light chain is a human light chain.

[0061] As used in this document, the terms “specifically ligase,” “specifically recognizes,” “immunospecifically binds,” and “immunospecifically recognizes” are analogous terms in the context of antibodies and refer to molecules that bind to an antigen (e.g., epitope or immune complex), as such binding is understood by one skilled in the art. For example, a molecule that specifically binds to an antigen may bind to other peptides or polypeptides, generally with lower affinity, as Petition 870250103709, dated 12 / 11 / 2025, p. 31 / 179 24 / 170 determined, for example, by immunoassays, BIAcore® instrument, KinExA 3000 (Sapidyne Instruments, Boise, ID) or other assays known in the art. In a specific embodiment, molecules that bind specifically to an antigen bind to the antigen with a Ka that is at least 2 logs (e.g., factors of 10), 2.5 logs, 3 logs, 4 logs, or greater than the Ka when the molecules bind non-specifically to another antigen.

[0062] As used in this document, the term “affinity” refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise indicated, as used in this document, “binding affinity” refers to the intrinsic binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd). Affinity can be measured by common methods known in the art, including those described in this document.

[0063] As used herein, the term “EU numbering system” refers to the EU numbering convention for the constant regions of an antibody, as described in Edelman, GM et al., Proc. Natl. Acad. USA, 63, 78-85 (1969) and Kabat et al, Sequences of Proteins of Immunological Interest, US Dept. Health and Human Services, 5th edition, 1991, each of which is incorporated herein by reference in its entirety.

[0064] As used in this document, the terms “treat,” “treating,” and “treatment” refer to the therapeutic or preventive measures described herein. “Treatment” methods employ the administration of an antibody to a subject with a disease or disorder, or predisposed to having such a disease or disorder, in order to prevent, cure, delay, reduce the severity of, or improve one or more symptoms of the disease or disorder or recurrent disease or disorder, or in order to prolong the survival of a subject beyond what would be expected in the absence of such treatment. Petition 870250103709, dated 12 / 11 / 2025, p. 32 / 179 25 / 170

[0065] As used in this document, the term “effective amount” in the context of administering a therapy to a subject refers to the amount of a therapy that achieves a desired prophylactic or therapeutic effect.

[0066] As used in this document, the term “subject” includes any human or non-human animal. In certain modalities, the subject is a human or non-human mammal. In certain modalities, the individual is a human.

[0067] As used in this document, with respect to an antibody or polynucleotide, the term “isolate” refers to an antibody or polynucleotide that is separated from one or more contaminants (e.g., polypeptides, polynucleotides, lipids, or carbohydrates, etc.) that are present in a natural source of the antibody or polynucleotide. All instances of “isolated antibodies” described in this document are further considered as antibodies that may be, but do not need to be, isolated. All instances of “isolated polynucleotides” described in this document are further considered as polynucleotides that may be, but do not need to be, isolated. All instances of “antibodies” described in this document are further considered as antibodies that may be, but do not need to be, isolated. All instances of “polynucleotides” described in this document are further considered as polynucleotides that may be, but do not need to be, isolated.

[0068] Determining the “percentage of identity” between two sequences (e.g., amino acid sequences or nucleic acid sequences) can be performed using a mathematical algorithm. A specific and non-limiting example of a mathematical algorithm used for comparing two sequences is the algorithm of Karlin S & Altschul SF (1990) PNAS 87: 22642268, modified as in Karlin S & Altschul SF (1993) PNAS 90: 5873 to 5877, each of which is incorporated herein by reference in its entirety. This algorithm is incorporated into the NBLAST and XBLAST programs of Altschul SF et al., (1990) J Mol Biol 215: 403, which is incorporated herein by reference in its entirety. BLAST nucleotide searches can be performed with the program parameters of Petition 870250103709, dated 12 / 11 / 2025, page 33 / 179 26 / 170 nucleotide NBLAST defined, for example, to score = 100, word length = 12 to obtain nucleotide sequences homologous to a nucleic acid molecule described in this document. Protein BLAST searches can be performed with the XBLAST program parameters defined, for example, to score 50, word length = 3 to obtain amino acid sequences homologous to a protein molecule described in this document. To obtain gapped alignments for comparison purposes, Gapped BLAST can be used as described in Altschul SF et al., (1997) Nuc Acids Res 25: 3389 to 3402, which is incorporated herein by reference in its entirety. Alternatively, PSI BLAST can be used to perform an iterated search that detects distant relationships between molecules (Id.).When using the BLAST, Gapped BLAST, and PSI Blast programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used (see, for example, the National Center for Biotechnology Information (NCBI) website, ncbi.nlm.nih.gov). Another specific and non-limiting example of a mathematical algorithm used for sequence comparison is the Myers and Miller algorithm, 1988, CABIOS 4:11-17, which is incorporated here by reference in its entirety. This algorithm is incorporated into the ALIGN program (version 2.0), which is part of the GCG sequence alignment software package. When using the ALIGN program to compare amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used.

[0069] The percentage of identity between two sequences can be determined using techniques similar to those described above, allowing or not allowing gaps. When calculating the percentage of identity, normally only exact matches are counted. Anti-PC Antibodies

[0070] In one aspect, the present disclosure provides polypeptides (e.g., antibodies) that bind specifically to PC. The amino acid sequences of exemplary antibodies are presented in Table 1. Petition 870250103709, dated 12 / 11 / 2025, page 34 / 179 27 / 170 TABLE 1: AMINO ACID SEQUENCES OF EXEMPLARY ANTIBODIES. Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB01_A06 1 181 369 428 484 523 591 656 PcOxP_DB01_A12 2 182 370 429 485 523 592 657 PcOxP_DB01_B01 3 183 371 428 486 523 593 658 PcOxP_DB01_B04 4 184 372 428 484 523 591 659 PcOxP_DB01_B05 5 185 373 429 484 523 594 659 PcOxP_DB01_B07 1 184 369 428 484 523 591 659 PcOxP_DB01_B08 6 184 374 430 484 523 591 659 PcOxP_DB01_B09 1 186 369 428 484 523 595 660 PcOxP_DB01_B11 7 187 375 428 487 523 596 659 PcOxP_DB01_C01 8 188 376 428 484 524 591 659 PcOxP_DB01_C03 9 189 377 428 484 523 591 661 PcOxP_DB01_C04 10 190 378 428 484 523 591 662 PcOxP_DB01_C05 4 191 372 428 484 523 597 658 PcOxP_DB01_C06 11 192 379 428 484 523 598 662 PcOxP_DB01_C08 12 193 372 428 488 525 599 659 PcOxP_DB01_C12 13 194 376 431 484 523 600 663 PcOxP_DB01_D02 14 195 380 432 484 523 591 664 PcOxP_DB01_D05 15 196 372 428 489 523 601 659 PcOxP_DB01_D08 16 184 381 428 490 523 591 659 PcOxP_DB01_D09 17 197 382 428 484 526 597 665 PcOxP_DB01_E04 18 198 381 428491 523 602 659 PcOxP_DB01_E05 20 201 376 433 484 529 603 662 PcOxP_DB01_F04 667 Petition 870250103709, dated 12 / 11 / 2025, page 35 / 179 28 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB01_G01 23 204 384 435 484 530 606 659 PcOxP_DB01_G09 24 205 369 436 484 523 607 659 PcOxP_DB01_G11 25 184 372 437 487 523 591 659 PcOxP_DB01_G12 4 206 372 428 484 523 608 659 PcOxP_DB01_H04 26 207 385 428 493 523 609 662 PcOxP_DB01_H08 27 208 386 428 484 531 591 663 PcOxP_DB01_H10 28 209 372 437 484 523 608 661 PcOxP_DB02_A06 9 210 377 428 484 523 610 659 PcOxP_DB02_A09 29 211 387 428 484 523 611 668 PcOxP_DB02_A10 30 212 385 428 484 523 611 658 PcOxP_DB02_A11 31 213 372 438 484 523 596 662 PcOxP_DB02_A12 32 214 388 428 494 523 612 667 PcOxP_DB02_B02 33 215 369 439 484 523 613 668 PcOxP_DB02_B06 34 216 389 428 484 523 591 669 PcOxP_DB02_B10 17 217 382 428 484 523 591 663 PcOxP_DB02_B12 1 218 369 428 484 523 614 659 PcOxP_DB02_C01 35 184 381 428 484 523 591 659 PcOxP_DB02_C02 36 184 376 440 495 523 591 659 PcOxP_DB02_C06 35 219 381 428 484 532 615 662 PcOxP_DB02_C09 35 220 381 428 484 523 616 670 PcOxP_DB02_C11 37184 390 441 484 523 591 659 PcOxP_DB02_D01 PcOxP_DB02_D10 9 223 377 428 484 533 595 659 PcOxP_DB02_E01 9 224 377 428 484 523 618 659 PcOxP_DB02_E06 40 184 392 432 484 523 591 659 PcOxP_DB02_E10 41 225 377 443 484 534 619 662 PcOxP_DB02_F02 8 226 376 428 484 535 620 659 Petition 870250103709, dated 12 / 11 / 2025, page 36 / 179 29 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB02_F07 42 227 393 428 484 536 621 659 PcOxP_DB02_F12 35 228 381 428 484 537 603 671 PcOxP_DB02_G06 43 229 383 444 489 523 622 659 PcOxP_DB02_G07 4 230 372 428 484 523 617 659 PcOxP_DB02_G09 9 231 377 428 484 523 623 659 PcOxP_DB02_H03 8 232 376 428 484 538 607 672 PcOxP_DB02_H10 1 233 369 428 484 523 616 671 PcOxP_DB03_A03 8 234 376 428 484 523 624 659 PcOxP_DB03_A08 44 184 394 428 484 523 591 659 PcOxP_DB03_A09 1 235 369 428 484 523 620 659 PcOxP_DB03_A11 45 236 383 444 496 523 625 660 PcOxP_DB03_B02 30 237 385 428 484 523 602 671 PcOxP_DB03_C03 46 184 376 434 484 523 591 659 PcOxP_DB03_C06 47 238 395 445 497 523 611 663 PcOxP_DB03_C11 48 239 396 446 487 523 626 670 PcOxP_DB03_C12 1 230 369 428 484 523 617 659 PcOxP_DB03_D01 49 190 392 428 484 523 591 662 PcOxP_DB03_D07 44 240 394 428 484 523 606 673 PcOxP_DB03_D08 50 184 393 428 498 523 591 659 PcOxP_DB03_D11 51 241 376 428 495 523 627 671 PcOxP_DB03_E01 52 242369 440 484 523 628 671 PcOxP_DB03_E02 53 243 397 428 484 539 591 662 PcOxP_DB03_E07 54 184 389 447 484 523 591 659 PcOxP_DB03_E08 55 244 398 448 492 523 591 670 PcOxP_DB03_E09 56 245 373 449 490 523 611 659 PcOxP_DB03_F01 57 246 399 428 484 537 613 671 PcOxP_DB03_F10 58 247 400 450 484 540 598 659 PcOxP_DB03_G02 59 248 401 428 484 541 591 659 Petition 870250103709, dated 12 / 11 / 2025, page 37 / 179 30 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB03_G03 60 249 390 428 484 542 629 659 PcOxP_DB03_G06 8 250 376 428 484 523 591 671 PcOxP_DB03_G07 61 184 400 428 499 523 591 659 PcOxP_DB03_G10 35 251 381 428 484 523 630 667 PcOxP_DB03_H03 62 252 384 429 484 543 631 659 PcOxP_DB03_H07 1 253 369 428 484 523 632 664 PcOxP_DB03_H08 63 254 402 436 484 523 597 661 PcOxP_DB03_H09 64 181 381 451 484 523 591 656 PcOxP_DB04_A07 65 255 403 428 484 523 633 659 PcOxP_DB04_A09 66 256 369 429 484 544 607 659 PcOxP_DB04_A10 67 257 404 429 484 523 630 659 PcOxP_DB04_A12 68 198 372 429 484 523 602 659 PcOxP_DB04_B06 35 258 381 428 484 523 591 665 PcOxP_DB04_B08 69 259 388 428 484 523 610 674 PcOxP_DB04_C03 70 260 405 451 484 523 634 671 PcOxP_DB04_C08 71 261 406 428 484 545 591 661 PcOxP_DB04_D08 72 262 400 428 484 523 635 667 PcOxP_DB04_F06 73 263 404 428 484 546 591 659 PcOxP_DB04_F11 74 264 384 432 500 523 636 664 PcOxP_DB04_G06 75 265 376 452 501 547 591 663 PcOxP_DB04_H03 76266 407 428 484 548 619 659 PcOxP_DB04_H07 PcOxP_DB04_H10 78 268 408 428 484 523 638 659 PcOxP_DB01_A03 1 269 369 428 484 523 591 659 PcOxP_DB01_A04 27 269 386 428 484 523 591 659 PcOxP_DB01_A05 79 269 369 428 497 523 591 659 PcOxP_DB01_A08 80 270 403 453 484 549 591 659 Petition 870250103709, dated 12 / 11 / 2025, page 38 / 179 31 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB01_B02 81 269 402 454 484 523 591 659 PcOxP_DB01_B03 22 269 383 428 484 523 591 659 PcOxP_DB01_B06 82 269 383 434 500 523 591 659 PcOxP_DB01_B10 83 271 376 455 502 550 591 675 PcOxP_DB01_B12 84 272 383 435 484 523 591 664 PcOxP_DB01_C07 1 273 369 428 484 523 602 659 PcOxP_DB01_C09 8 274 376 428 484 551 591 659 PcOxP_DB01_C10 8 275 376 428 484 552 591 659 PcOxP_DB01_D01 22 276 383 428 484 553 591 676 PcOxP_DB01_D04 8 277 376 428 484 554 591 659 PcOxP_DB01_D06 85 278 376 428 490 523 591 676 PcOxP_DB01_D07 86 279 369 428 503 555 606 659 PcOxP_DB01_D10 87 269 409 428 484 523 591 659 PcOxP_DB01_D11 88 280 383 428 504 556 591 659 PcOxP_DB01_D12 89 269 369 434 484 523 591 659 PcOxP_DB01_E01 60 281 390 428 484 523 637 677 PcOxP_DB01_E02 90 269 369 456 484 523 591 659 PcOxP_DB01_E03 91 282 370 457 484 557 591 659 PcOxP_DB01_E07 22 283 383 428 484 558 591 659 PcOxP_DB01_E08 92 269 404 458 499 523 591 659 PcOxP_DB01_E09 93 284410 428 484 523 591 677 PcOxP_DB01_E10 94 285 383 459 484 553 639 659 PcOxP_DB01_F01 95 286 407 428 489 549 591 667 PcOxP_DB01_F03 96 269 374 434 484 523 591 659 PcOxP_DB01_F06 73 287 404 428 484 559 617 666 PcOxP_DB01_F07 97 288 411 460 505 523 591 672 PcOxP_DB01_F08 68 289 372 429 484 523 606 659 PcOxP_DB01_F11 98 269 383 428 485 523 591 659 Petition 870250103709, dated 12 / 11 / 2025, page 39 / 179 32 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB01_F12 99 290 386 460 490 523 601 659 PcOxP_DB01_G02 100 291 412 455 493 523 592 670 PcOxP_DB01_G03 4 292 372 428 484 560 591 667 PcOxP_DB01_G04 4 289 372 428 484 523 606 659 PcOxP_DB01_G05 101 284 383 461 484 523 591 677 PcOxP_DB01_G06 66 289 369 429 484 523 606 659 PcOxP_DB01_G07 89 293 369 434 484 530 591 659 PcOxP_DB01_G10 102 294 376 437 484 561 603 666 PcOxP_DB01_H01 103 269 383 462 500 523 591 659 PcOxP_DB01_H02 22 295 383 428 484 562 591 659 PcOxP_DB01_H03 104 296 400 463 484 523 616 660 PcOxP_DB01_H06 105 297 376 464 484 523 602 677 PcOxP_DB01_H07 106 270 400 434 506 549 591 659 PcOxP_DB01_H09 107 269 369 436 507 523 591 659 PcOxP_DB02_A04 67 269 404 429 484 523 591 659 PcOxP_DB02_A05 62 298 384 429 484 523 616 659 PcOxP_DB02_B04 66 269 369 429 484 523 591 659 PcOxP_DB02_B07 108 299 377 465 484 523 630 660 PcOxP_DB02_B09 109 300 413 459 484 563 591 659 PcOxP_DB02_C03 110 301 369 452 484 523 591 663PcOxP_DB02_C04 111 302 414 466 484 523 640 659 PcOxP_DB02_C05 112 269 373 428 484 523 591 659 PcOxP_DB02_C08 113 303 415 428 489 564 591 659 PcOxP_DB02_C10 PcOxP_DB02_D02 114 306 369 428 491 565 591 662 PcOxP_DB02_D03 115 307 403 458 508 523 642 664 PcOxP_DB02_E02 116 269 392 467 484 523 591 659 Petition 870250103709, dated 12 / 11 / 2025, page 40 / 179 33 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB02_E03 117 308 369 452 509 566 643 659 PcOxP_DB02_E08 118 269 388 468 490 523 591 659 PcOxP_DB02_E09 110 309 369 452 484 523 644 667 PcOxP_DB02_E11 119 310 377 440 484 567 606 659 PcOxP_DB02_E12 120 311 370 428 484 523 591 656 PcOxP_DB02_F04 121 269 384 467 487 523 591 659 PcOxP_DB02_F06 122 312 392 469 510 568 591 659 PcOxP_DB02_F09 123 289 378 464 484 523 606 659 PcOxP_DB02_F10 9 313 377 428 484 569 645 659 PcOxP_DB02_F11 124 314 416 434 484 523 603 659 PcOxP_DB02_G02 120 289 370 428 484 523 606 659 PcOxP_DB02_G03 125 315 370 428 511 570 628 678 PcOxP_DB02_G04 110 316 369 452 484 571 630 663 PcOxP_DB02_G05 126 317 376 428 502 572 591 664 PcOxP_DB02_H02 127 318 417 428 484 523 591 665 PcOxP_DB02_H04 49 319 392 428 484 573 591 670 PcOxP_DB02_H05 128 320 376 428 512 523 646 659 PcOxP_DB02_H06 9 321 377 428 484 574 591 670 PcOxP_DB02_H07 22 322 383 428 484 523 647 667 PcOxP_DB02_H08 129 323 381 428 493 575 591 659PcOxP_DB02_H09 130 269 383 470 501 523 591 659 PcOxP_DB03_A04 131 324 404 471 484 537 591 659 PcOxP_DB03_A05 132 325 418 428 484 523 635 670 PcOxP_DB03_A06 133 326 383 472 513 576 591 659 PcOxP_DB03_A07 134 327 419 428 484 577 606 659 PcOxP_DB03_A10 53 328 397 428 484 523 648 679 PcOxP_DB03_A12 135 272 372 473 484 523 591 664 PcOxP_DB03_B01 136 329 383 474 484 523 592 659 Petition 870250103709, dated 12 / 11 / 2025, page 41 / 179 34 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB03_B03 4 301 372 428 484 523 591 663 PcOxP_DB03_B06 137 330 420 434 484 523 595 659 PcOxP_DB03_B07 138 269 370 428 514 523 591 659 PcOxP_DB03_B08 1 284 369 428 484 523 591 677 PcOxP_DB03_B09 22 331 383 428 484 523 600 659 PcOxP_DB03_B10 139 269 369 475 484 523 591 659 PcOxP_DB03_B11 140 332 421 436 484 523 649 664 PcOxP_DB03_B12 141 269 378 452 484 523 591 659 PcOxP_DB03_C01 142 333 376 476 515 578 641 659 PcOxP_DB03_C04 143 334 376 428 504 523 591 667 PcOxP_DB03_C08 144 335 422 469 484 523 606 660 PcOxP_DB03_C10 101 298 383 461 484 523 616 659 PcOxP_DB03_D02 1 336 369 428 484 523 650 656 PcOxP_DB03_D03 145 269 369 428 516 523 591 659 PcOxP_DB03_D10 146 337 405 460 484 523 618 659 PcOxP_DB03_D12 147 269 413 431 484 523 591 659 PcOxP_DB03_E03 17 338 382 428 484 579 621 671 PcOxP_DB03_E04 22 320 383 428 484 523 646 659 PcOxP_DB03_E11 4 339 372 428 484 580 591 660 PcOxP_DB03_E12 148 340 406 429 484 527 591 659PcOxP_DB03_F02 149 341 383 428 517 581 595 659 PcOxP_DB03_F03 150 342 377 437 518 582 640 664 PcOxP_DB03_F05 151 343 369 477 487 583 651 659 PcOxP_DB03_F07 152 344 403 464 484 534 591 659 PcOxP_DB03_F09 94 289 383 459 484 523 606 659 PcOxP_DB03_F11 153 345 369 454 484 584 591 671 PcOxP_DB03_G01 Petition 870250103709, dated 12 / 11 / 2025, page 42 / 179 35 / 170 Anticorpo SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB03_G11 22 348 383 428 484 585 591 659 PcOxP_DB03_G12 89 282 369 434 484 557 591 659 PcOxP_DB03_H02 156 349 382 434 484 523 649 659 PcOxP_DB03_H10 157 296 424 479 484 523 616 660 PcOxP_DB04_A04 158 350 376 429 484 586 591 666 PcOxP_DB04_A05 159 329 425 428 484 523 592 659 PcOxP_DB04_A11 24 351 369 436 484 587 652 659 PcOxP_DB04_B01 160 352 403 428 520 588 638 659 PcOxP_DB04_B07 161 269 417 460 484 523 591 659 PcOxP_DB04_B10 162 353 409 460 484 523 623 664 PcOxP_DB04_B11 163 269 404 452 484 523 591 659 PcOxP_DB04_B12 1 354 369 428 484 523 591 682 PcOxP_DB04_C09 164 355 383 428 521 553 653 659 PcOxP_DB04_C10 165 269 372 480 493 523 591 659 PcOxP_DB04_C11 1 356 369 428 484 523 654 659 PcOxP_DB04_D01 166 357 369 477 484 523 648 659 PcOxP_DB04_D05 167 358 369 481 484 560 591 659 PcOxP_DB04_D07 110 334 369 452 484 523 591 667 PcOxP_DB04_D09 87 359 409 428 484 580 606 659 PcOxP_DB04_D10 168 360 384 452 484 589 593 661PcOxP_DB04_D12 169 269 377 482 484 523 591 659 PcOxP_DB04_E05 170 269 410 483 484 523 591 659 PcOxP_DB04_E06 171 269 384 428 489 523 591 659 PcOxP_DB04_E08 172 361 426 429 484 523 622 659 PcOxP_DB04_E12 8 362 376 428 484 523 637 676 PcOxP_DB04_F01 173 304 427 428 484 523 591 671 PcOxP_DB04_F03 174 269 373 452 506 523 591 659 PcOxP_DB04_F05 1 363 369 428 484 590 622 659 Petition 870250103709, dated 12 / 11 / 2025, page 43 / 179 36 / 170 Antibody SEQ ID NO: VH CDRH1 CDRH2 CDRH3 VL CDRL1 CDRL2 CDRL3 PcOxP_DB04_G01 175 364 369 429 521 555 591 661 PcOxP_DB04_G03 176 365 405 428 522 523 615 672 PcOxP_DB04_G05 177 269 376 428 510 523 591 659 PcOxP_DB04_G08 178 366 384 428 484 523 626 668 PcOxP_DB04_G09 179 269 ​​410 429 484 523 591 659 PcOxP_DB04_G11 180 367 400 452 484 523 655 659 PcOxP_DB04_H01 89 368 369 434 484 523 606 680

[0071] In certain embodiments, the present disclosure provides an antibody that binds specifically to PC, the antibody comprising a VH domain comprising one, two, or all three CDRs of a VH domain set forth in Table 1. In certain embodiments, the antibody comprises CDRH1 of a VH domain set forth in Table 1. In certain embodiments, the antibody comprises CDRH2 of a VH domain set forth in Table 1. In certain embodiments, the antibody comprises CDRH3 of a VH domain set forth in Table 1.

[0072] In certain embodiments, flash disclosure provides an antibody that binds specifically to PC, the antibody comprising a VL domain comprising one, two, or all three CDRs of a VL domain disclosed in Table 1. In certain embodiments, the antibody comprises CDRL1 of a VL domain set forth in Table 1. In certain embodiments, the antibody comprises CDRL2 of a VL domain set forth in Table 1. In certain embodiments, the antibody comprises CDRL3 of a VL domain set forth in Table 1.

[0073] The individual CDRs of an antibody disclosed in this document can be determined according to any CDR numbering scheme known in the art.

[0074] In certain modalities, one or more of the CDRs of Petition 870250103709, dated 12 / 11 / 2025, page 44 / 179 37 / 170 An antibody disclosed in this document can be determined in accordance with Kabat et al., J. Biol. Chem. 252, 6609 to 6616 (1977) and Kabat et al., Sequences of protein of immunological interest (1991), each of which is incorporated herein by reference in its entirety.

[0075] In certain embodiments, the present disclosure provides antibodies that bind specifically to PC and comprise CDRs of an antibody disclosed in Table 1 herein, as determined by the Kabat numbering scheme.

[0076] In certain embodiments, one or more of the CDRs of an antibody disclosed in this document may be determined according to the Chothia numbering scheme, which refers to the location of immunoglobulin structural loops (see, for example, Chothia C & Lesk AM, (1987), J Mol Biol 196: 901 to 917; Al-Lazikani B et al., (1997) J Mol Biol 273: 927 to 948; Chothia C et al., (1992) J Mol Biol 227: 799 to 817; Tramontano A et al., (1990) J Mol Biol 215(1): 175 to 182; and U.S. Patent No. 7,709,226, all of which are incorporated herein by reference in their entirety).

[0077] In certain embodiments, the present disclosure provides antibodies that bind specifically to PC and comprise CDRs of an antibody disclosed in Table 1 herein, as determined by the Chothia numbering system.

[0078] In certain embodiments, one or more of the CDRs of an antibody disclosed in this document may be determined in accordance with MacCallum RM et al., (1996) J Mol Biol 262: 732 to 745, incorporated herein by reference in full. See also, for example, Martin A. “Protein Sequence and Structure Analysis of Antibody Variable Domains,” in Antibody Engineering, Kontermann and Dübel, eds., Chapter 31, pp. 422 to 439, Springer-Verlag, Berlin (2001), incorporated herein by reference in full.

[0079] In certain embodiments, the present disclosure provides antibodies that bind specifically to PC and comprise CDRs of an antibody disclosed in Table 1 herein, as determined by the system of Petition 870250103709, dated 12 / 11 / 2025, p. 45 / 179 38 / 170 MacCallum sizing.

[0080] In certain embodiments, the CDRs of an antibody disclosed herein may be determined according to the IMGT numbering system as described in: Lefranc MP, (1999) The Immunologist 7: 132 to 136; Lefranc MP et al., (1999) Nucleic Acids Res 27: 209 to 212, each of which is incorporated herein by reference in its entirety; and Lefranc MP et al., (2009) Nucleic Acids Res 37: D1006-D1012.

[0081] In certain embodiments, flash disclosure provides antibodies that bind specifically to PC and comprise CDRs of an antibody disclosed in Table 1 herein, as determined by the IMGT numbering system.

[0082] In certain embodiments, the CDRs of an antibody disclosed herein can be determined according to the AbM numbering scheme, which refers to AbM hypervariable regions, which represent a compromise between Kabat CDRs and Chothia structural loops, and are used by the Oxford Molecular (Oxford Molecular Group, Inc.) AbM antibody modeling software, which is incorporated herein by reference in its entirety.

[0083] In certain embodiments, flash disclosure provides antibodies that bind specifically to PC and comprise CDRs of an antibody disclosed in Table 1 herein, as determined by the AbM numbering scheme.

[0084] In certain embodiments, the CDRs of an antibody disclosed herein may be determined in accordance with the AHo numbering system, as described in Honegger and Plückthun, A., J. Mol. Biol. 309:657 to 670 (2001), which is incorporated herein by reference in its entirety.

[0085] In certain embodiments, flash disclosure provides antibodies that bind specifically to PC and comprise CDRs of an antibody disclosed in Table 1 herein, as determined by the AHo numbering system.

[0086] In certain modalities, the individual CDRs of a Petition 870250103709, dated 12 / 11 / 2025, page 46 / 179 39 / 170 antibodies disclosed here are independently determined according to one of the Kabat, Chothia, MacCallum, IMGT, AHo or AbM numbering schemes, or by structural analysis of the molecule, wherein the structural analysis identifies residues in the variable region(s) predicted to make contact with an epitope region of PC.

[0087] In certain embodiments, this disclosure provides an antibody or polypeptide that specifically binds to PC, comprising a VH comprising the amino acid sequences CDRH1, CDRH2 and CDRH3 from any of the VH amino acid sequences presented in SEQ ID NOs: 1-180, and a VL comprising the amino acid sequences CDRL1, CDRL2 and CDRL3 from any of the VL amino acid sequences presented in SEQ ID NOs: 181-368, wherein each CDR is independently determined according to one of the Kabat, Chothia, MacCallum, IMGT, AHo or AbM numbering schemes, or by structural analysis of the molecule, wherein the structural analysis identifies the residues in the variable region(s) that are expected to come into contact with an epitope region of PC.

[0088] In certain embodiments, the present disclosure provides an antibody or polypeptide that binds specifically to PC, wherein the antibody or polypeptide comprises the amino acid sequences CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 of the amino acid sequences VH and VL established in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; 8 and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; 16 and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 and 212; 31 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; 35 and 184; 36 and 184; 35 and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; and 224; 40 and 184; 41 and 225; 8 and 226; 42 and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8 and 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243; 54 and 184; 55 and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248; 60 and 249; 8 and 250; 61 and 184; Petition 870250103709, dated 12 / 11 / 2025, page 47 / 179 40 / 170 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; 35 and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265; 76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; 83 and 271; 84 and 272; 1 and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; 87 and 269; 88 and 280; 89 and 269; 60 and 281; 90 and 269; 91 and 282; and 283; 92 and 269; 93 and 284; 94 and 285; 95 and 286; 96 and 269; 73 and 287; 97 and 288;68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; 4 and 289; 101 and 284; 66 and 289; 89 and293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; 66 and 269; 108 and 299; 109 and 300; 110 and 301; 111 and 302; 112 and 269; 113 and 303; 1 and 304; 72 and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309; 119 and 310; 120 and 311; 121 and 269; 122 and 312; 123 and 289; 9 and 313; 124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317; 127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324; 132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330; 138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 and 333; 143 and 334; 144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 and 354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 and 363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368, respectively.

[0089] In certain embodiments, the present disclosure provides an antibody or polypeptide that binds specifically to PC, wherein the antibody or polypeptide comprises a VH comprising the amino acid sequences CDRH1, CDRH2 and CDRH3 set forth in SEQ ID NOs: 369, 428 and 484; 370, 429 and 485; 371, 428 and 486; 372, 428 and 484; 373, 429 and 484; 374, 430 and 484; 375, 428 and 487; 376, 428 and 484; 377, 428 and 484; 378, 428 and 484; 379, 428 and 484; 372, 428 and 488; 376, 431 and 484; 380, 432 and 484; 372, 428 and 489; 381, 428 and 490; 382, 428 and 484; 381, 428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and Petition 870250103709, dated 12 / 11 / 2025, page 48 / 179 41 / 170 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381,428 and 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484; 393, 428 and 498; 376, 428 and 495; 369, 440 and 484; 397, 428 and 484; 389, 447 and 484; 398, 448 and 492; 373, 449 and 490; 399, 428 and 484; 400, 450 and 484; 401, 428 and 484; 390, 428 and 484; 400, 428 and 499; 384, 429 and 484; 402, 436 and 484; 381, 451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and 500;376, 452 and 501; 407, 428 and 484; 375, 428 and 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489;374, 434 and 484; 411, 460 and 505; 383, 428 and 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484; 413, 459 and 484; 369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484;369, 452 and 509; 388, 468 and 490; 377, 440 and 484; 370, 428 and 484; 384, 467 and 487; 392,469 and 510; 378, 464 and 484; 416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381,428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484;370, 428 and 514; 369, 475 and 484; 421,436 and 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, 434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520; 417, 460 and 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484; 384, 428 and 489; 426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or Petition 870250103709, dated 12 / 11 / 2025, page 49 / 179 42 / 170 400, 452 and 484, respectively.

[0090] In certain embodiments, the present disclosure provides an antibody or polypeptide that specifically binds to PC, wherein the antibody or polypeptide comprises a VL comprising the amino acid sequences CDRL1, CDRL2 and CDRL3 set forth in the SEQ ID NOs: 523, 591 and 656; 523, 592 and 657; 523, 593 and 658; 523, 591 and 659; 523, 594 and 659; 523, 595 and 660; 523, 596 and 659; 524, 591 and 659; 523, 591 and 661; 523, 591 and 662; 523, 597 and 658; 523, 598 and 662; 525, 599 and 659; 523, 600 and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531, 591 and 663; 523, 608 and 661; 523, 610 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659; 534, 619 and 662;535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659; 523, 617 and 659; 523, 623 and 659; 538, 607 and 672; 523, 616 and 671; 523, 624 and 659; 523, 620 and 659; 523, 625 and 660; 523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661;523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676;555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 and 659; 523, 592 and 670; 560, 591 and 667; 530, 591 and 659; 561, 603 and 666; 562, 591 and 659; 523, 616 and 660; 523, 602 and 677; 523, 616 and 659; 523, 630 and 660; 563, 591 and 659; 523, 640 and 659; 564, 591 and 659; 523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571, 630 and 663; 572, 591 and 664; 573, 591 and 670; 523, 646 and 659; Petition 870250103709, dated 12 / 11 / 2025, page 50 / 179 43 / 170 574, 591 and 670; 523, 647 and 667; 575, 591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660; 527, 591 and 659; 581, 595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659; 560, 591 and 659; 580, 606 and 659; 589, 593 and 661; 523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672; 523, 626 and 668; 523, 655 and 659; or 523, 606 and 680, respectively.

[0091] In certain embodiments, the present disclosure provides an antibody or polypeptide that binds specifically to PC, wherein the antibody or polypeptide comprises a VH comprising CDRH1, CDRH2 and CDRH3 regions, and a VL comprising CDRL1, CDRL2 and CDRL3 regions, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 regions comprise the amino acid sequences set forth in the SEQ ID NOs: 369, 428, 484, 523, 591 and 656; 370, 429, 485, 523, 592 and 657; 371, 428, 486, 523, 593 and 658; 372, 428, 484, 523, 591 and 659; 373, 429, 484, 523, 594 and 659; 369, 428, 484, 523, 591 and 659; 374, 430, 484, 523, 591 and 659; 369, 428, 484, 523, 595 and 660; 375, 428, 487, 523, 596 and 659; 376, 428, 484, 524, 591 and 659; 377, 428, 484, 523, 591 and 661; 378, 428, 484, 523, 591 and 662; 372, 428, 484, 523, 597 and 658; 379, 428, 484, 523, 598 and 662; 372, 428, 488, 525, 599 and 659; 376, 431,484, 523, 600 and 663; 380, 432, 484, 523, 591 and 664; 372, 428, 489, 523, 601 and 659; 381, 428, 490, 523, 591 and 659; 382, 428, 484, 526, 597 and 665; 381, 428, 491, 523, 602 and 659; 369, 428, 484, 527, 591 and 661; 377, 428, 492, 528, 591 and 662; 376, 433, 484, 529, 603 and 662; 383, 434, 484, 523, 604 and 666; 383, 428, 484, 523, 605 and 667; 384, 435, 484, 530, 606 and 659; 369, 436, 484, 523, 607 and 659; 372, 437, 487, 523, 591 and 659; 372, 428, 484, 523, 608 and 659; 385, 428, 493, 523, 609 and 662; 386, 428, 484, 531, 591 and 663; 372, 437, 484, 523, 608 and 661; 377, 428, 484, 523, 610 and 659; 387, 428, 484, 523, 611 and 668; 385, 428, 484, 523, 611 and 658; 372, 438, 484, 523, 596 and 662; 388, 428, 494, 523, 612 and 667; 369, 439, 484, 523, 613 and 668; 389, 428, 484, 523, 591 and 669; 382, 428, 484, 523, 591 and Petition 870250103709, dated 12 / 11 / 2025, page 51 / 179 44 / 170 663; 369, 428, 484, 523, 614 and 659; 381, 428, 484, 523, 591 and 659; 376, 440, 495, 523, 591 and 659; 381, 428, 484, 532, 615 and 662; 381, 428, 484, 523, 616 and 670; 390, 441, 484, 523, 591 and 659; 370, 442, 484, 523, 591 and 668; 391, 428, 484, 523, 617 and 671; 377, 428, 484, 533, 595 and 659; 377, 428, 484, 523, 618 and 659; 392, 432, 484, 523, 591 and 659; 377, 443, 484, 534, 619 and 662; 376, 428, 484, 535, 620 and 659; 393, 428, 484, 536, 621 and 659; 381, 428, 484, 537, 603 and 671; 383, 444, 489, 523, 622 and 59; 372, 428, 484, 523, 617 and 659; 377, 428, 484, 523, 623 and 659; 376, 428, 484, 538, 607 and 672; 369, 428, 484, 523, 616 and 671; 376, 428, 484, 523, 624 and 659; 394, 428, 484, 523, 591 and 659; 369, 428, 484, 523, 620 and 659; 383, 444, 496, 523, 625 and 660; 385, 428, 484, 523, 602 and 671; 376, 434, 484, 523, 591 and 659; 395, 445, 497, 523, 611 and 663; 396, 446, 487, 523, 626 and 670; 369, 428, 484, 523, 617 and 659; 392, 428, 484, 523, 591 and 662; 394, 428, 484, 523, 606 and 673; 393, 428, 498, 523, 591 and 659; 376, 428, 495, 523, 627 and 671; 369, 440, 484, 523, 628 and 671; 397, 428, 484, 539, 591 and 662; 389, 447, 484, 523, 591 and 659; 398, 448, 492, 523, 591 and 670; 373, 449, 490, 523, 611 and 659; 399, 428, 484, 537, 613 and 671; 400, 450, 484, 540, 598 and 659; 401, 428, 484, 541, 591 and 659; 390, 428, 484, 542, 629 and 659; 376, 428, 484, 523, 591 and 671; 400, 428, 499, 523, 591 and 659; 381, 428, 484, 523, 630 and 667; 384, 429, 484, 543, 631 and 659; 369, 428, 484, 523, 632 and 664; 402, 436, 484, 523, 597 and 661; 381, 451, 484, 523, 591 and 656; 403, 428, 484, 523, 633 and 659; 369, 429, 484, 544, 607 and 659; 404, 429, 484, 523, 630 and 659; 372, 429, 484, 523, 602 and 659; 381, 428, 484, 523, 591 and 665; 388, 428, 484, 523, 610 and 674; 405, 451, 484, 523, 634 and 671; 406, 428, 484, 545, 591 and 661; 400, 428, 484, 523, 635 and 667; 404, 428, 484, 546, 591 and 659; 384, 432, 500, 523, 636 and 664; 376, 452, 501, 547, 591 and 663; 407, 428, 484, 548, 619 and 659; 375, 428, 484, 523, 637 and 659; 372, 428, 484, 523, 607 and 659; 408, 428, 484, 523, 638 and 659; 386, 428, 484, 523, 591 and 659; 369, 428, 497, 523, 591 and 659; 403, 453, 484, 549, 591 and 659; 402, 454, 484, 523, 591 and 659; 383, 428, 484, 523, 591 and 659; 383, 434, 500, 523, 591 and 659; 376, 455, 502, 550, 591 and 675; 383, 435, 484, 523, 591 and 664; 369, 428, 484, 523, 602 and 659; 376, 428, 484, 551, 591 and 659; 376, 428, 484, 552, 591 and 659; 383, 428, 484, 553, 591 and 676; 376, 428, 484, 554, 591 and 659; 376, 428, 490, 523, 591 and 676; 369, 428, 503, 555, 606 and 659; 409, Petition 870250103709, dated 12 / 11 / 2025, page 52 / 179 45 / 170 428, 484, 523, 591 and 659; 383, 428, 504, 556, 591 and 659; 369, 434, 484, 523, 591 and 659; 390, 428, 484, 523, 637 and 677; 369, 456, 484, 523, 591 and 659; 370, 457,484, 557, 591 and 659; 383, 428, 484, 558, 591 and 659; 404, 458, 499, 523, 591 and 659; 410, 428, 484, 523, 591 and 677; 383, 459, 484, 553, 639 and 659; 407, 428, 489, 549, 591 and 667; 374, 434, 484, 523, 591 and 659; 404, 428, 484, 559, 617 and 666; 411, 460,505, 523, 591 and 672; 372, 429, 484, 523, 606 and 659; 383, 428, 485, 523, 591 and 659; 386, 460, 490, 523, 601 and 659; 412, 455, 493, 523, 592 and 670; 372, 428, 484, 560, 591 and 667; 372, 428, 484, 523, 606 and 659; 383, 461, 484, 523, 591 and 677; 369, 429,484, 523, 606 and 659; 369, 434, 484, 530, 591 and 659; 376, 437, 484, 561, 603 and 666; 383, 462, 500, 523, 591 and 659; 383, 428, 484, 562, 591 and 659; 400, 463, 484, 523, 616 and 660; 376, 464, 484, 523, 602 and 677; 400, 434, 506, 549, 591 and 659; 369, 436,507, 523, 591 and 659; 404, 429, 484, 523, 591 and 659; 384, 429, 484, 523, 616 and 659; 369, 429, 484, 523, 591 and 659; 377, 465, 484, 523, 630 and 660; 413, 459, 484, 563, 591 and 659; 369, 452, 484, 523, 591 and 663; 414, 466, 484, 523, 640 and 659; 373, 428,484, 523, 591 and 659; 415, 428, 489, 564, 591 and 659; 369, 428, 484, 523, 591 and 671; 400, 428, 484, 523, 641 and 677; 369, 428, 491, 565, 591 and 662; 403, 458, 508, 523, 642 and 664; 392, 467, 484, 523, 591 and 659; 369, 452, 509, 566, 643 and 659; 388, 468,490, 523, 591 and 659; 369, 452, 484, 523, 644 and 667; 377, 440, 484, 567, 606 and 659; 370, 428, 484, 523, 591 and 656; 384, 467, 487, 523, 591 and 659; 392, 469, 510, 568, 591 and 659; 378, 464, 484, 523, 606 and 659; 377, 428, 484, 569, 645 and 659; 416, 434,484, 523, 603 and 659; 370, 428, 484, 523, 606 and 659; 370, 428, 511, 570, 628 and 678; 369, 452, 484, 571, 630 and 663; 376, 428, 502, 572, 591 and 664; 417, 428, 484, 523, 591 and 665; 392, 428, 484, 573, 591 and 670; 376, 428, 512, 523, 646 and 659; 377, 428,484, 574, 591 and 670; 383, 428, 484, 523, 647 and 667; 381, 428, 493, 575, 591 and 659; 383, 470, 501, 523, 591 and 659; 404, 471,484, 537, 591 and 659; 418, 428, 484, 523, 635 and 670; 383, 472, 513, 576, 591 and 659; 419, 428, 484, 577, 606 and 659; 397, 428,484, 523, 648 and 679; 372, 473, 484, 523, 591 and 664; 383, 474, 484, 523, 592 and 659; 372, 428, 484, 523, 591 and 663; 420, 434, 484, 523, 595 and 659; 370, 428, 514, 523, 591 and 659; 369, 428, 484, 523, 591 and 677; 383, 428, 484, 523, 600 and 659; 369, 475,484, 523, 591 and 659; 421, 436, 484, 523, 649 and 664; 378, 452, 484, 523, 591 and 659; 376, Petition 870250103709, dated 12 / 11 / 2025, page 53 / 179 46 / 170 476, 515, 578, 641 and 659; 376, 428, 504, 523, 591 and 667; 422, 469, 484, 523, 606 and 660; 383, 461, 484, 523, 616 and 659; 369, 428, 484, 523, 650 and 656; 369, 428, 516, 523, 591 and 659; 405, 460, 484, 523, 618 and 659; 413, 431, 484, 523, 591 and 659; 382, 428, 484, 579, 621 and 671; 383, 428, 484, 523, 646 and 659; 372, 428, 484, 580, 591 and 660; 406, 429, 484, 527, 591 and 659; 383, 428, 517, 581, 595 and 659; 377, 437, 518, 582, 640 and 664; 369, 477, 487, 583, 651 and 659; 403, 464, 484, 534, 591 and 659; 383, 459, 484, 523, 606 and 659; 369, 454, 484, 584, 591 and 671; 372, 478, 519, 523, 591 and 680; 423, 429, 484, 523, 591 and 681; 383, 428, 484, 585, 591 and 659; 369, 434, 484, 557, 591 and 659; 382, ​​434, 484, 523, 649 and 659; 424, 479, 484, 523, 616 and 660; 376, 429, 484, 586, 591 and 666; 425, 428, 484, 523, 592 and 659; 369, 436, 484, 587, 652 and 659; 403, 428, 520, 588, 638 and 659; 417, 460, 484, 523, 591 and 659; 409, 460, 484, 523, 623 and 664; 404, 452, 484, 523, 591 and 659; 369, 428, 484, 523, 591 and 682; 383, 428, 521, 553, 653 and 659; 372, 480, 493, 523, 591 and 659; 369, 428, 484, 523, 654 and 659; 369, 477, 484, 523, 648 and 659; 369, 481, 484, 560, 591 and 659; 369, 452, 484, 523, 591 and 667; 409, 428, 484, 580, 606 and 659; 384, 452, 484, 589, 593 and 661; 377, 482, 484, 523, 591 and 659; 410, 483, 484, 523, 591 and 659; 384, 428, 489, 523, 591 and 659; 426, 429, 484, 523, 622 and 659; 376, 428, 484, 523, 637 and 676; 427, 428, 484, 523, 591 and 671; 373, 452, 506, 523, 591 and 659; 369, 428, 484, 590, 622 and 659; 369, 429, 521, 555, 591 and 661; 405, 428, 522, 523, 615 and 672; 376, 428, 510, 523, 591 and 659; 384, 428, 484, 523, 626 and 668; 410, 429, 484, 523, 591 and 659; 400, 452, 484, 523, 655 and 659; or 369, 434, 484, 523, 606 and 680, respectively.

[0092] In certain embodiments, the present disclosure provides an antibody or polypeptide that specifically binds to PC, comprising a VH comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95% or 100% (for example, at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%) identical to any of the amino acid sequences set forth in SEQ ID NOs: 1-180. In certain embodiments, the instant disclosure provides an antibody or polypeptide that specifically binds to PC, comprising a VH comprising any of the amino acid sequences shown in SEQ ID NOs: 1-180. In certain Petition 870250103709, dated 12 / 11 / 2025, p. 54 / 179 47 / 170 modes, the amino acid sequence of VH consists of any of the amino acid sequences set forth in SEQ ID NOs: 1-180.

[0093] In certain embodiments, the present disclosure provides an antibody or polypeptide that binds specifically to PC, comprising a VL comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95% or 100% (for example, at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%) identical to any of the amino acid sequences set forth in SEQ ID Nos: 181-368. In certain embodiments, the present disclosure provides an antibody or polypeptide that binds specifically to PC, comprising a VL comprising any of the amino acid sequences set forth in SEQ ID Nos: 181-368. In certain embodiments, the amino acid sequence of the VL consists of any of the amino acid sequences established in SEQ ID NOs: 181-368.

[0094] In certain embodiments, flash disclosure provides an antibody or polypeptide that binds specifically to PC, comprising a VH comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95% or 100% (e.g., at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%) identical to any of the amino acid sequences set forth in the SEQ ID NOs, at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%) identical to any of the amino acid sequences shown in the SEQ ID NOs: 1-180, and a VL comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95% or 100% (for example, at least 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%) identical to any of the amino acid sequences defined in SEQ ID NOs: 181-368.In certain embodiments, the flash revelation provides an antibody or polypeptide that binds specifically to PC, comprising a VH comprising any of the amino acid sequences shown in SEQ ID NOs: 1-180, and a VL comprising any of the amino acid sequences shown in SEQ ID NOs: 181-368. In certain embodiments, the amino acid sequence of the VH consists of any of the amino acid sequences. Petition 870250103709, dated 12 / 11 / 2025, p. 55 / 179 48 / 170 presented in SEQ ID Nos: 1-180; and the amino acid sequence of VL consists of any of the amino acid sequences presented in SEQ ID Nos: 181368.

[0095] In certain embodiments, this disclosure provides an antibody or polypeptide that binds specifically to PC, comprising the amino acid sequences VH and VL set forth in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; 21 and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 and 212; 31 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; 35 and 184; 36 and 184; and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; 9 and 224; 40 and 184; 41 and 225; 8 and 226; 42 and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8 and 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243; 54 and 184; 55 and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248; 60 and 249; 8 and 250; 61 and 184; 35 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; 35 and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265; 76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; and 271; 84 and 272; 1 and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; and 269; 88 and 280; 89 and 269; 60 and 281; 90 and 269; 91 and 282; 22 and 283; 92 and 269;93 and 284; 94 and 285; 95 and 286; 96 and 269; 73 and 287; 97 and 288; 68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; 4 and 289; 101 and 284; 66 and 289; 89 and 293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; 66 and 269; 108 and 299; 109 and 300; 110 and 301; 111 and 302; 112 and 269; 113 and 303; 1 and 304; 72 and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309; 119 and 310; 120 and 311; 121 and 269; 122 and 312; 123 and 289; 9 and 313; 124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317; 127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324; 132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330; 138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 Petition 870250103709, dated 12 / 11 / 2025, page 56 / 179 49 / 170 and 333; 143 and 334; 144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 and 354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 e363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368, respectively.

[0096] In certain embodiments, the amino acid sequences of VH and VL consist of the amino acid sequences established in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; 8 and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; 16 and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; 21 and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 and 212; 31 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; and 184; 36 and 184; 35 and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; 9e 224; 40 and 184; 41 and 225; 8 and 226; 42 and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8e 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243; 54 e184; and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248; 60 and 249; 8 and 250; 61 and 184;35 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265;76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; 83 and 271; 84 and 272; 1 and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; 87 and 269; 88 and 280; 89 and 269; 60 and 281; 90 and 269; 91 and 282; 22 and 283; 92 and 269; 93 and 284; 94 and 285; 95 and 286; 96 and 269; 73 and 287; 97 and 288; 68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; 4 and 289; 101 and 284; 66 and 289; 89 and 293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; and 269; 108 and 299; 109 and 300; 110 and 301; 111 and 302; 112 and 269; 113 and 303; 1 and 304; and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309; 119 and Petition 870250103709, dated 12 / 11 / 2025, p. 57 / 179 50 / 170 310; 120 and 311; 121 and 269; 122 and 312; 123 and 289; 9 and 313; 124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317; 127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324; 132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330; 138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 and 333; 143 and 334; 144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 and 354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 and 363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368, respectively.

[0097] Any antibody format can be used in the antibodies disclosed herein. In certain embodiments, the antibody is a single-chain antibody or single-chain Fv (scFv). In certain embodiments, the antibody is an scFv fused with an Fc region (scFv-Fc). In certain embodiments, the antibody is a Fab fragment. In certain embodiments, the antibody is an F(ab')2 fragment.

[0098] In certain embodiments, the antibody or polypeptide disclosed in this document is a multispecific antibody (e.g., a bispecific antibody) that binds specifically to PC and a second antigen.

[0099] In certain embodiments, the antibody or polypeptide disclosed herein is conjugated to a cytotoxic agent, cytostatic agent, toxin, radionuclide, or detectable marker. In certain embodiments, the cytotoxic agent is capable of inducing the extermination or destruction of a cell in contact with it. In certain embodiments, the cytostatic agent is capable of preventing or substantially reducing the proliferation and / or inhibiting the activity or function of a cell in contact with it. In certain embodiments, the cytotoxic agent or cytostatic agent is a chemotherapeutic agent. In certain embodiments, the radionuclide is selected from the group consisting of isotopes 3H, 14C, 32P, 35S, 36Cl, 51Cr, 57Co, 58Co, 59Fe, 67Cu, 90Y, 99Tc, 11¼117Lu, 121I, 124I, 125I, 131I, 198Au, 211At, 213Bi, 225Ac and 186Re. In certain Petition 870250103709, dated 12 / 11 / 2025, page 58 / 179 51 / 170 modalities, the detectable label comprises a fluorescent chemical portion or a click chemical cable.

[0100] Any constant region of immunoglobulin (Ig) may be used in the polypeptides and antibodies disclosed herein. In certain embodiments, the Ig region is a human immunoglobulin molecule IgG, IgE, IgM, IgD, IgA, or IgY, any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) or any subclass (e.g., IgG2a and IgG2b) of the immunoglobulin molecule.

[0101] In certain embodiments, the present disclosure provides a polypeptide (e.g., an antibody) that binds specifically to PC, the polypeptide comprising a constant heavy chain region, optionally selected from the group consisting of human IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2.

[0102] In certain embodiments, flash disclosure provides a polypeptide (e.g., an antibody) that specifically binds to PC, the polypeptide comprising a heavy chain constant region that is a variant of a wild-type heavy chain constant region, wherein the variant heavy chain constant region binds to an FcyR with lower affinity than the wild-type heavy chain constant region binds to the FcyR.

[0103] In certain embodiments, the instant disclosure provides an antibody that binds specifically to PC, the antibody comprising a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 683 or 684. In certain embodiments, the instant disclosure provides an antibody that binds specifically to PC, the antibody comprising a heavy chain constant region consisting of the amino acid sequence of SEQ ID NO: 683 or 684. In certain embodiments, the instant disclosure provides an antibody that binds specifically to PC, the antibody comprising a heavy chain constant region of IgG1 of any allotype or isoallotype. In certain embodiments, the present disclosure provides an antibody that binds specifically to PC, the antibody comprising a heavy chain constant region of IgG1 of an allotype selected from the group consisting of G1m1(a), G1m2(x), G1m3(f) and Petition 870250103709, dated 12 / 11 / 2025, p. 59 / 179 52 / 170 G1m17(z). See, for example, Jefferis and Lefranc (2009) mAbs 1(4): 332-338.

[0104] In certain embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into an Fc region (e.g., a CH2 domain (residues 231-340 of human IgG1)) and / or a CH3 domain (residues 341-447 of human IgG1), numbered according to the EU numbering system) and / or a hinge region (residues 216-230, numbered according to the EU numbering system) of an antibody described in this document, to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding and / or antigen-dependent cellular cytotoxicity.

[0105] In certain embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of an antibody described in this document, such that the number of cysteine ​​residues in the hinge region is altered (e.g., increased or decreased) as described, for example, in U.S. Patent No. 5,677,425, which is incorporated herein by reference in its entirety. The number of cysteine ​​residues in the hinge region may be altered to, for example, facilitate the assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the antibody.

[0106] In a particular embodiment, one, two, or more amino acid mutations (e.g., substitutions, insertions, or deletions) are introduced into a constant region of IgG or its FcRn binding fragment (preferably an Fc or Fc hinge fragment) to alter (e.g., decrease or increase) the antibody half-life in vivo. See, for example, International Publications Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631; and U.S. Patents Nos. 5,869,046, 6,121,022, 6,277,375, and 6,165,745, all of which are incorporated herein by reference in their entirety, for examples of mutations that will alter (e.g., decrease or increase) the half-life of an antibody in vivo. In certain forms, one, two, or more amino acid mutations (e.g., substitutions, insertions, or deletions) are introduced into a constant region of Petition 870250103709, dated 12 / 11 / 2025, p. 60 / 179 53 / 170 IgG or its FcRn-binding fragment (preferably an Fc or Fc hinge fragment) to decrease the antibody half-life in vivo. In other embodiments, one, two, or more amino acid mutations (e.g., substitutions, insertions, or deletions) are introduced into a constant region of IgG or its FcRn-binding fragment (preferably an Fc or Fc hinge fragment) to increase the antibody half-life in vivo. In one specific embodiment, antibodies may have one or more amino acid mutations (e.g., substitutions) in the second constant domain (CH2) (residues 231-340 of human IgG1) and / or in the third constant domain (CH3) (residues 341-447 of human IgG1), numbered according to the EU numbering system.In a specific embodiment, the constant region of the IgG1 antibody described in this document comprises a methionine (M) to tyrosine (Y) substitution at position 252, a serine (S) to threonine (T) substitution at position 254, and a threonine (T) to glutamic acid (E) substitution at position 256, numbered according to the EU numbering system. See U.S. Patent No. 7,658,921, which is incorporated herein by reference in its entirety. This type of mutant IgG, referred to as the “YTE mutant”, has been shown to have a half-life four times longer compared to wild-type versions of the same antibody (see Dall'Acqua WF et al., (2006) J Biol Chem 281: 23514 to 23524, which is incorporated herein by reference in its entirety).In certain embodiments, an antibody comprises a constant region of IgG comprising one, two, three or more amino acid substitutions of amino acid residues at positions 251-257, 285-290, 308-314, 385-389 and 428-436, numbered according to the EU numbering system.

[0107] In certain embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into an Fc region (e.g., a CH2 domain (residues 231-340 of human IgG1)) and / or a CH3 domain (residues 341-447 of human IgG1, numbered according to the EU numbering system) and / or a hinge region (residues 216-230, numbered according to the EU numbering system) of an antibody described in this document, to increase or decrease the antibody's affinity for a Petition 870250103709, dated 12 / 11 / 2025, page 61 / 179 54 / 170 Fc receptor (e.g., an activated Fc receptor) on the surface of an effector cell. Mutations in the Fc region of an antibody that decrease or increase the affinity of an antibody for an Fc receptor and techniques for introducing such mutations into the Fc receptor or a fragment thereof are known to those skilled in the art. Examples of mutations in the Fc receptor of an antibody that can be made to alter the affinity of the antibody for an Fc receptor are described in, for example, Smith P et al., (2012) PNAS 109: 6181-6186, U.S. Patent No. 6,737,056 and International Publications Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631, all of which are incorporated herein by reference in their entirety.

[0108] In certain embodiments, the antibody comprises a heavy chain constant region that is a variant of a wild-type heavy chain constant region, wherein the variant heavy chain constant region binds to FcyRIIB with higher affinity than the wild-type heavy chain constant region binds to FcyRIIB. In certain embodiments, the variant heavy chain constant region is a variant human heavy chain constant region, for example, a variant of the human IgG1 heavy chain constant region, a variant of the human IgG2 heavy chain constant region, or a variant of the human IgG4 heavy chain constant region. In certain embodiments, the variant human IgG heavy chain constant region comprises one or more of the following amino acid mutations, according to the EU numbering system: G236D, P238D, S239D, S267E, L328F, and L328E.In certain embodiments, the variant constant region of the human IgG heavy chain comprises a set of amino acid mutations selected from the group consisting of: S267E and L328F; P238D and L328E; P238D and one or more substitutions selected from the group consisting of E233D, G237D, H268D, P271G and A330R; P238D, E233D, G237D, H268D, P271G and A330R; G236D and S267E; S239D and S267E; V262E, S267E and L328F; and V264E, S267E and L328F, according to the EU numbering system. In certain modalities, FcyRIIB is expressed in a selected cell from the group consisting of macrophages, monocytes, B cells, dendritic cells, endothelial cells, and activated T cells. Petition 870250103709, dated 12 / 11 / 2025, page 62 / 179 55 / 170

[0109] In a further embodiment, one, two or more amino acid substitutions are introduced into an Fc region of the IgG constant region to alter the effector function(s) of the antibody. For example, one or more amino acids selected from amino acid residues 234, 235, 236, 237, 239, 243, 267, 292, 297, 300, 318, 320, 322, 328, 330, 332 and 396, numbered according to the EU numbering system, may be substituted for a different amino acid residue, so that the antibody has altered affinity for an effector ligand, but retains the antigen-binding capacity of the parental antibody. The effector ligand for which the affinity is altered may be, for example, an Fc receptor or the C1 component of complement. This approach is described in more detail in U.S. Patents Nos. 5,624,821 and 5,648,260, each of which is incorporated herein by reference in its entirety.In certain embodiments, deletion or inactivation (through point mutations or other means) of a constant region domain can reduce the binding to the Fc receptor of the circulating antibody, thus increasing tumor localization. See, for example, U.S. Patents Nos. 5,585,097 and 8,591,886, each of which is incorporated herein by reference in its entirety, for a description of mutations that delete or inactivate the constant region and thus increase tumor localization. In certain embodiments, one or more amino acid substitutions can be introduced into the Fc region of an antibody described herein to remove potential glycosylation sites in the Fc region, which can reduce Fc receptor binding (see, for example, Shields RL et al., (2001) J Biol Chem 276: 6591 to 604, which is incorporated herein by reference in its entirety).In several embodiments, one or more of the following mutations in the constant region of an antibody described herein may be made: an N297A substitution; an N297Q substitution; an L234A substitution; an L234F substitution; an L235A substitution; an L235F substitution; an L235V substitution; an L237A substitution; an S239D substitution; an E233P substitution; an L234V substitution; an L235A substitution; a C236 deletion; a P238A substitution; an S239D substitution; an F243L substitution; a D265A substitution; an S267E substitution; an L328F substitution; an R292P substitution; a Y300L substitution; a... Petition 870250103709, dated 12 / 11 / 2025, page 63 / 179 56 / 170 replacement A327Q; a replacement P329A; a replacement A330L; a replacement I332E; or a replacement P396L, numbered according to the EU numbering system.

[0110] In certain embodiments, a selected mutation from the group consisting of D265A, P329A and a combination thereof, numbered according to the EU numbering system, may be made in the constant region of an antibody described in this document. In certain embodiments, a selected mutation from the group consisting of L235A, L237A and a combination thereof, numbered according to the EU numbering system, may be made in the constant region of an antibody described in this document. In certain embodiments, a selected mutation from the group consisting of S267E, L328F and a combination thereof, numbered according to the EU numbering system, may be made in the constant region of an antibody described in this document.In certain embodiments, a selected mutation from the group consisting of S239D, I332E, optionally A330L, and a combination thereof, numbered according to the EU numbering system, may be made in the constant region of an antibody described in this document. In certain embodiments, a selected mutation from the group consisting of L235V, F243L, R292P, Y300L, P396L, and a combination thereof, numbered according to the EU numbering system, may be made in the constant region of an antibody described in this document. In certain embodiments, a selected mutation from the group consisting of S267E, L328F, and a combination thereof, numbered according to the EU numbering system, may be made in the constant region of an antibody described in this document.

[0111] In a specific embodiment, an antibody described in this document comprises the constant region of an IgG1 with an N297Q or N297A amino acid substitution, numbered according to the EU numbering system. In certain embodiments, an antibody described in this document comprises the constant region of an IgG1 with a mutation selected from the group consisting of D265A, P329A and a combination thereof, numbered from Petition 870250103709, dated 12 / 11 / 2025, p. 64 / 179 57 / 170 according to the EU numbering system. In another embodiment, an antibody described in this document comprises the constant region of an IgGi with a mutation selected from the group consisting of L234A, L235A and a combination thereof, numbered according to the EU numbering system. In another embodiment, an antibody described in this document comprises the constant region of an IgG1 with a mutation selected from the group consisting of L234F, L235F, N297A and a combination thereof, numbered according to the EU numbering system. In certain embodiments, the amino acid residues in the constant region of an antibody described in this document at the positions corresponding to the L234, L235 and D265 positions in a human IgG1 heavy chain, numbered according to the EU numbering system, are not L, L, and D, respectively. This approach is described in detail in International Publication No. WO 14 / 108483, which is incorporated herein by reference in its entirety.In certain embodiments, the amino acids corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain are F, E, and A; or A, A, and A, respectively, numbered according to the EU numbering system.

[0112] In certain embodiments, one or more amino acids selected from amino acid residues 329, 331, and 322 in the constant region of an antibody described herein, numbered according to the EU numbering system, may be replaced by a different amino acid residue, such that the antibody has altered binding to C1q and / or reduced or abolished complement-dependent cytotoxicity (CDC). This approach is described in more detail in U.S. Patent No. 6,194,551 (Idusogie et al.), which is incorporated herein by reference in its entirety. In certain embodiments, one or more amino acid residues at amino acid positions 231 to 238 in the N-terminal region of the CH2 domain of an antibody described herein are altered to thereby alter the antibody's ability to bind complement, numbered according to the EU numbering system.This approach is described in greater detail in International Publication No. WO 94 / 29351, which is incorporated herein by reference in its entirety. In certain embodiments, the Fc region of an antibody described herein... Petition 870250103709, dated 12 / 11 / 2025, p. 65 / 179 Document 58 / 170 is modified to increase the antibody's ability to mediate antibody-dependent cellular cytotoxicity (ADCC) and / or to increase the antibody's affinity for an Fcy receptor by mutating one or more amino acids (e.g., by introducing amino acid substitutions) at the following positions: 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301, 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 328, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, ​​​​388, 389, 398, 414, 416, 419, 430, 434, 435,437, 438, or 439, numbered according to the EU numbering system. This approach is described in greater detail in International Publication No. WO 00 / 42072, which is incorporated herein by reference in its entirety.

[0113] In certain embodiments, an antibody described herein comprises a modified constant region of an IgG1, wherein the modification increases the antibody's ability to mediate antibody-dependent cellular cytotoxicity (ADCC). In certain embodiments, 0.1, 1, or 10 pg / mL of the antibody is capable of inducing cell death in at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60% of PC-expressing cells within 1, 2, or 3 hours, as assessed by methods described herein and / or known to a person skilled in the art. In certain embodiments, the modified constant region of an IgG1 comprises S239D and I332E substitutions, numbered according to the EU numbering system. In certain embodiments, the modified constant region of an IgG1 comprises S239D, A330L and I332E substitutions, numbered according to the EU numbering system.In certain embodiments, the modified constant region of an IgG1 comprises L235V, F243L, R292P, Y300L, and P396L substitutions, numbered according to the EU numbering system. In certain embodiments, the antibody is capable of inducing cell death in effector T cells and Tregs, wherein the percentage of Tregs undergoing cell death is greater than the percentage of effector T cells undergoing cell death by at least 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 2 times, 2.5 times, 3 times, 3.5 times, 4 times, 4.5 times. Petition 870250103709, dated 12 / 11 / 2025, page 66 / 179 59 / 170 times or 5 times.

[0114] In certain embodiments, an antibody described in this document comprises the constant region of an IgG4 antibody and the serine at amino acid residue 228 of the heavy chain, numbered according to the EU numbering system, is replaced by proline. In certain embodiments, flash disclosure provides an antibody that specifically binds to PC, the antibody comprising a heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 684.

[0115] In certain embodiments, any of the mutations or constant region modifications described in this document may be introduced into one or both heavy chain constant regions of an antibody described in this document having two heavy chain constant regions. PHARMACEUTICAL COMPOSITIONS

[0116] Compositions comprising an anti-PC antibody disclosed herein having the desired degree of purity in a physiologically acceptable carrier, excipient or stabilizer are provided in this document (see, for example, Remington's Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA). Acceptable carriers, excipients or stabilizers are not toxic to receptors at the dosages and concentrations used and include buffers such as phosphate, citrate and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens, such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight polypeptides (less than about 10 residues); proteins, such as serum albumin, gelatin, or immunoglobulins;hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates, including glucose, mannose or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions, such as sodium; Petition 870250103709, dated 12 / 11 / 2025, page 67 / 179 60 / 170 metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants, such as TWEEN™, PLURONIC™, or polyethylene glycol (PEG).

[0117] In a specific embodiment, the pharmaceutical compositions comprise an anti-PC antibody disclosed herein and, optionally, one or more additional prophylactic or therapeutic agents, in a pharmaceutically acceptable carrier. In a specific embodiment, the pharmaceutical compositions comprise an anti-PC antibody disclosed herein, and optionally one or more additional prophylactic or therapeutic agents, in a pharmaceutically acceptable carrier. In certain embodiments, the antibody is the only active ingredient included in the pharmaceutical composition. The pharmaceutical compositions described herein may be useful for decreasing or inhibiting PC activity and treating a condition, such as an inflammatory disorder. In certain embodiments, the present disclosure refers to a pharmaceutical composition of the present disclosure comprising an anti-PC antibody of the present disclosure for use as a medicament.In another embodiment, the present disclosure refers to a pharmaceutical composition of the present disclosure for use in a method for treating an inflammatory disorder.

[0118] Pharmaceutically acceptable carriers used in parenteral preparations include aqueous vehicles, non-aqueous vehicles, antimicrobial agents, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, emulsifying agents, sequestering or chelating agents, and other pharmaceutically acceptable substances. Examples of aqueous vehicles include sodium chloride injection, Ringer's injection, isotonic dextrose injection, sterile water injection, dextrose, and Ringer's lactate injection. Non-aqueous parenteral vehicles include fixed vegetable oils, cottonseed oil, corn oil, sesame oil, and peanut oil.Antimicrobial agents in bacteriostatic or fungistatic concentrations may be added to parenteral preparations packaged in multi-dose containers, including phenols or cresols, mercurials, benzyl alcohol, chlorobutanol, methyl and propyl p-hydroxybenzoic acid esters, thimerosal. Petition 870250103709, dated 12 / 11 / 2025, page 68 / 179 61 / 170 benzalkonium chloride and benzethonium chloride. Isotonic agents include sodium chloride and dextrose. Buffers include phosphate and citrate. Antioxidants include sodium bisulfate. Local anesthetics include procaine hydrochloride. Suspending and dispersing agents include sodium carboxymethylcellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone. Emulsifying agents include Polysorbate 80 (TWEEN® 80). A metal ion chelating or sequestering agent includes EDTA. Pharmaceutical carriers also include ethyl alcohol, polyethylene glycol, and propylene glycol for water-miscible vehicles; and sodium hydroxide, hydrochloric acid, citric acid, or lactic acid for pH adjustment.

[0119] A pharmaceutical composition may be formulated for any route of administration to a subject. Specific examples of routes of administration include intranasal, oral, pulmonary, transdermal, intradermal, and parenteral. Parenteral administration, characterized by subcutaneous, intramuscular, or intravenous injection, is also contemplated in this document. Injectables may be prepared in conventional forms, such as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Injectables, solutions, and emulsions also contain one or more excipients. Suitable excipients are, for example, water, saline solution, dextrose, glycerol, or ethanol.In addition, if desired, the pharmaceutical compositions to be administered may also contain small amounts of non-toxic auxiliary substances, such as humectants or emulsifiers, pH buffering agents, stabilizers, solubility enhancers and other similar agents, such as, for example, sodium acetate, sorbitan monolaurate, triethanolamine oleate and cyclodextrins.

[0120] Preparations for parenteral administration of antibodies include sterile solutions ready for injection, sterile dry soluble products, such as lyophilized powders, ready to be combined with a solvent immediately before use, including hypodermic tablets, sterile suspensions ready for injection, sterile dry insoluble products ready to be combined with a vehicle immediately before use, and sterile emulsions. Petition 870250103709, dated 12 / 11 / 2025, page 69 / 179 62 / 170 solutions can be aqueous or non-aqueous.

[0121] If administered intravenously, suitable carriers include physiological saline or phosphate-buffered saline (PBS) and solutions containing thickening and solubilizing agents such as glucose, polyethylene glycol and polypropylene glycol, and mixtures thereof.

[0122] Topical mixtures containing an antibody are prepared as described for local and systemic administration. The resulting mixture may be a solution, suspension, emulsion or the like and may be formulated as creams, gels, ointments, emulsions, solutions, elixirs, lotions, suspensions, tinctures, pastes, foams, aerosols, irrigations, sprays, suppositories, bandages, dermal patches or any other formulations suitable for topical administration.

[0123] An anti-PC antibody disclosed herein may be formulated as an aerosol for topical application, such as by inhalation (see, for example, U.S. Patents Nos. 4,044,126, 4,414,209 and 4,364,923, which describe aerosols for administering a steroid useful for the treatment of inflammatory diseases, particularly asthma, and are incorporated herein by reference in their entirety). These formulations for administration to the respiratory tract may be in the form of an aerosol or solution for a nebulizer, or as a microfine powder for insufflations, alone or in combination with an inert carrier, such as lactose. In this case, the particles of the formulation will, in certain embodiments, have diameters smaller than 50 microns, in certain embodiments smaller than 10 microns.

[0124] An anti-PC antibody disclosed in this document may be formulated for local or topical application, such as for topical application to the skin and mucous membranes, such as the eyes, in the form of gels, creams and lotions and for application to the eyes or for intracisternal or intraspinal application. Topical administration is contemplated for transdermal distribution and also for administration to the eyes or mucous membranes, or for inhalation therapies. Nasal solutions of the antibody may also be administered alone or in combination with Petition 870250103709, dated 12 / 11 / 2025, p. 70 / 179 63 / 170 other pharmaceutically acceptable excipients.

[0125] Transdermal patches, including iontophoretic and electrophoretic devices, are well known to those skilled in the art and can be used to administer an antibody. For example, such patches are disclosed in U.S. Patents Nos. 6,267,983, 6,261,595, 6,256,533, 6,167,301, 6,024,975, 6,010,715, 5,985,317, 5,983,134, 5,948,433 and 5,860,957, all of which are incorporated herein by reference in their entirety.

[0126] In certain embodiments, a pharmaceutical composition comprising an antibody described herein is a lyophilized powder, which may be reconstituted for administration as solutions, emulsions, and other mixtures. It may also be reconstituted and formulated as solids or gels. The lyophilized powder is prepared by dissolving the antibody described herein, or a pharmaceutically acceptable derivative thereof, in a suitable solvent. In certain embodiments, the lyophilized powder is sterile. The solvent may contain an excipient that improves the stability or another pharmacological component of the powder or reconstituted solution prepared from the powder. Excipients that may be used include, but are not limited to, dextrose, sorbitol, fructose, corn syrup, xylitol, glycerin, glucose, sucrose, or other suitable agent.The solvent may also contain a buffer, such as citrate, sodium or potassium phosphate, or another buffer known to those skilled in the art, in certain embodiments, with a pH close to neutral. Subsequent sterile filtration of the solution followed by lyophilization under standard conditions known to those skilled in the art provides the desired formulation. In certain embodiments, the resulting solution will be dispensed into vials for lyophilization. Each vial will contain a single dose or multiple doses of the compound. The lyophilized powder can be stored under suitable conditions, such as between 4°C and room temperature. Reconstitution of this lyophilized powder with water for injection provides a formulation for use in parenteral administration. For reconstitution, the lyophilized powder is added to sterile water or another suitable carrier. The exact amount depends on the compound selected. Such an amount can be determined empirically. Petition 870250103709, dated 12 / 11 / 2025, page 71 / 179 64 / 170

[0127] The anti-PC antibodies disclosed in this document and other compositions provided herein may also be formulated to target a specific tissue, recipient, or other area of ​​the body of the subject to be treated. Many of these targeting methods are well known to those skilled in the art. All such targeting methods are contemplated herein for use in the present compositions. For non-limiting examples of targeting methods, see, for example, U.S. Patents Nos. 6,316,652, 6,274,552, 6,271,359, 6,253,872, 6,139,865, 6,131,570, 6,120,751, 6,071,495, 6,060,082, 6,048,736, 6,039,975, 6,004,534, 5,985,307, 5,972,366, 5,900,252, 5,840,674, 5,759,542 and 5,709,874, all of which are incorporated herein by reference in their entirety.

[0128] Compositions to be used for in vivo administration may be sterile. This is easily achieved by filtration through, for example, sterile filtration membranes. METHODS OF USE AND USES

[0129] In another aspect, the present disclosure provides a method of treating a subject using the anti-PC antibodies disclosed herein. Any disease or disorder in a subject that would benefit from decreased oxidized phospholipid function can be treated using the anti-PC antibodies disclosed herein.

[0130] In certain embodiments, the anti-PC antibodies disclosed herein are particularly useful for inhibiting PC activity in an individual. In certain embodiments, the anti-PC antibodies disclosed herein are particularly useful for inhibiting PC inflammatory activity in an individual. In certain embodiments, the anti-PC antibodies disclosed herein are particularly useful for treating an inflammatory disorder or a degenerative disease. In certain embodiments, the anti-PC antibodies disclosed herein can be used as an anti-inflammatory agent and / or as an anti-atherosclerotic agent. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat pain. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat osteoporosis. In certain embodiments, the anti-PC antibodies disclosed herein can Petition 870250103709, dated 12 / 11 / 2025, page 72 / 179 65 / 170 can be used to treat fibrotic diseases, including, without limitation, pulmonary fibrosis. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat diseases caused by NETosis, including, without limitation, anti-neutrophil cytoplasmic antibody (ANCA) vasculitis and type I diabetes. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat chronic obstructive pulmonary disease (COPD). In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat acute respiratory diseases, acute fulminant pneumonias, or other similar disorders. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat severe asthma. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat patients with acute hepatitis or non-alcoholic steatohepatitis (NASH) and metabolic syndrome.In certain embodiments, the anti-PC antibodies disclosed herein can be used as an anti-atherosclerotic agent to treat cardiovascular disease and calcified aortic stenosis (CAS). In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat patients with acute coronary syndromes or "crescent angina." In certain embodiments, the anti-PC antibodies disclosed herein can be used as a proactive measure in the treatment of high-risk patients, for example, patients who are prone to stroke or developing atherosclerosis. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat high-risk patients with coronary artery disease (CAD).Thus, the anti-PC antibodies disclosed herein can be used to treat inflammatory diseases and disorders, cardiovascular diseases, and diseases associated with oxidized phospholipids, including, without limitation, atherosclerosis, acute coronary syndrome, acute myocardial infarction, myocardial infarction (heart attack), stable and unstable angina pectoris, aneurysms, coronary artery disease (CAD), ischemic heart disease, ischemic myocardium, cardiac death and sudden cardiac death, cardiomyopathy, congestive heart failure, heart failure, stenosis, peripheral arterial disease (PAD), intermittent claudication, critical limb ischemia, and stroke. See U.S. Patent No. 11,008,381, which is. Petition 870250103709, dated 12 / 11 / 2025, page 73 / 179 66 / 170 incorporated herein by reference in its entirety.

[0131] In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat cardiovascular diseases, atherosclerosis, rheumatoid arthritis, osteoarthritis, lung tissue damage (e.g., caused by smoking), brain damage, apoptosis, senescence, Crohn's disease, ulcerative colitis, fatty liver disease (e.g., NASH), and non-alcoholic fatty liver disease (NAFLD). Thus, the anti-PC antibodies disclosed herein may be used to treat inflammatory diseases and disorders, cardiovascular diseases, liver diseases and disorders (e.g., NASH, NAFLD), and diseases associated with stress and oxidative damage. In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat non-alcoholic fatty liver disease. In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat non-alcoholic steatohepatitis (NASH).In certain embodiments, the anti-PC antibodies disclosed herein can be used to inhibit the progression of NAFLD to NASH. In certain embodiments, the anti-PC antibodies disclosed herein can be used to treat or inhibit atherogenesis. See U.S. Patent No. 11,168,148, which is incorporated herein by reference in its entirety.

[0132] In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat reperfusion injury. In certain embodiments, reperfusion injury comprises organ reperfusion injury. In certain embodiments, reperfusion injury comprises ischemic reperfusion injury. In certain embodiments, organ reperfusion injury is induced by an ischemic event (e.g., myocardial infarction-induced reperfusion injury).In certain modalities, the anti-PC antibodies disclosed herein may be used to treat an individual who is at risk of experiencing or has experienced an ischemic event, including, without limitation, an ischemic event associated with a selected condition from the group consisting of cerebral ischemia; intestinal ischemia; spinal cord ischemia; cardiovascular ischemia; myocardial ischemia associated with myocardial infarction; myocardial ischemia associated with congestive heart failure (CHF); ischemia associated with related macular degeneration. Petition 870250103709, dated 12 / 11 / 2025, p. 74 / 179 67 / 170 at age (AME); hepatic ischemia; renal / renal ischemia; dermal ischemia; vasoconstriction-induced tissue ischemia; penile ischemia as a consequence of priapism and erectile dysfunction; ischemia associated with thromboembolic disease; ischemia associated with microvascular disease; ischemia associated with thrombosis; and ischemia associated with diabetic ulcers, gangrenous conditions, post-traumatic syndrome, cardiac arrest resuscitation, hypothermia, peripheral nerve damage, and neuropathies. In certain modalities, the anti-PC antibodies disclosed herein may be used to treat an individual at risk of or who has suffered an ischemic event resulting from an induced injury, including, without limitation, surgery, transplantation, accidental trauma, and mechanical support devices.In certain modalities, the anti-PC antibodies disclosed in this document may be used to treat an individual at risk of or who has suffered an ischemic event resulting from cardiac surgery, renal surgery, brain surgery, hepatic surgery, and bypass surgery. In certain modalities, the anti-PC antibodies disclosed herein may be used to treat acute ischemic stroke. In certain modalities, the anti-PC antibodies disclosed herein may be used to treat indications caused by reperfusion, including organ transplantation such as liver, heart, and kidney.In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat a disease associated with thrombosis, including, without limitation, sickle cell disease, deep vein thrombosis, pulmonary embolism, cardiac embolism, hypercoagulability state, thrombophilia, Factor V Leiden, antithrombin III deficiency, protein C deficiency, protein S deficiency, prothrombin gene mutation (G20210A), hyperhomocysteinemia, antiphospholipid antibody (APS) syndrome, anticardiolipin antibody thrombosis syndrome (ACLA), and lupus anticoagulant syndrome (LA). In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat or inhibit atherogenesis. See U.S. Patent Application Serial No. 16 / 759,331, which is incorporated herein by reference in its entirety.

[0133] In certain modalities, the anti-PC antibodies disclosed herein may be used to treat a disease or disorder mediated by Petition 870250103709, dated 12 / 11 / 2025, p. 75 / 179 68 / 170 toll-like receptor 2 (TLR2), including, without limitation, Kawasaki disease, including IVIG-refractory Kawasaki disease, type 2 diabetes, rheumatoid arthritis, dermatological disease, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, Graves' disease, Sjögren's syndrome, autoimmune thyroid diseases or vasculitis. See U.S. Patent Application Serial No. 16 / 965,271, which is incorporated herein by reference in its entirety.

[0134] In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat bacterial infections. In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat neuroinflammatory diseases, including, without limitation, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat Huntington's disease, frontotemporal dementia (FTD), multiple sclerosis (MS), clinically isolated syndrome (CIS), and other demyelinating diseases of the central nervous system. In certain embodiments, the anti-PC antibodies disclosed herein may be used to treat eye diseases, including, without limitation, age-related macular degeneration (AMD) and geographic atrophy (GA).

[0135] In certain modalities, these methods also comprise administering an additional therapeutic agent to the subject. In certain modalities, the additional therapeutic agent is an HMG-CoA reductase inhibitor (statin), immunosuppressant, ezetimide, perixosome, nicotinic acid, squalene inhibitor, proliferation-activated receptor agonist (PPAR), cholesteryl ester transfer protein (CETP) inhibitor, ApoA-1 Milano, corticosteroid, nonsteroidal anti-inflammatory drug, steroidal anti-inflammatory drug, analgesic, growth factor, anti-atherosclerosis agent, antiproliferative agent, HSP, Beta-2 glycoprotein-I and any derivative or analogue thereof.

[0136] HMGCoA reductase inhibitors (statins) are well-known medications that effectively reduce low-density lipoprotein (LDL) cholesterol levels by inhibiting the enzyme that regulates the rate of cholesterol production and increasing the clearance of LDL cholesterol (LDL). 69 / 170 C) present in the blood produced by the liver. Non-limiting examples of commonly prescribed statins include Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, and Simvastatin.

[0137] Non-limiting examples of immunosuppressive agents include biological products such as infliximab, abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, ixekizumab, natalizumab, rituximab, secukinumab, tocilizumab, ustekinumab, canakinumab and vedolizumab, calcineurin inhibitors such as cyclosporine and tacrolimus, mTOR inhibitors such as sirolimus and everolimus, inosine monophosphate dehydrogenase (IMDH) inhibitors such as azathioprine, leflunomide and mycophenolate, methotrexate, monoclonal antibodies such as daclizumab and basiliximab, muromonab-CD3 and Janus kinase inhibitors such as tofacitinib.

[0138] Ezetimibe is the first of a new class of cholesterol absorption inhibitors that potently and selectively inhibits the absorption of dietary and biliary cholesterol at the brush border of the intestinal epithelium, without affecting the absorption of triglycerides or fat-soluble vitamins. Thus, ezetimibe reduces the overall supply of cholesterol to the liver, secondarily inducing increased expression of LDL receptors, resulting in greater removal of LDL-C from the plasma.

[0139] The peroxisome is a single-membrane organelle present in almost all eukaryotic cells. One of the most important metabolic processes of the peroxisome is the β-oxidation of long-chain and very long-chain fatty acids. The peroxisome is also involved in bile acid synthesis, cholesterol synthesis, plasmalogen synthesis, amino acid metabolism, and purine metabolism.

[0140] Nicotinic acid is a known agent that reduces total cholesterol, LDL cholesterol, and triglyceride levels, while increasing high-density lipoprotein (HDL) levels. There are three types of nicotinic acid-based drugs: immediate-release, timed-release, and extended-release. Nicotinic acid, or niacin, the water-soluble B vitamin, improves all Petition 870250103709, dated 12 / 11 / 2025, p. 77 / 179 70 / 170 lipoproteins when administered in doses well above vitamin requirements.

[0141] Squalene, an isoprenoid compound structurally similar to beta-carotene, is an intermediate metabolite in cholesterol synthesis. In humans, about 60% of dietary squalene is absorbed. It is transported in the serum, usually in association with very low-density lipoproteins, and is ubiquitously distributed in human tissues, with the highest concentration in the skin, where it is a major component of skin surface lipids. Squalene inhibitors (e.g., monooxygenase and synthase) act as inhibitors of cholesterol biosynthesis.

[0142] Proliferation-activated receptor (PPAR) agonists, for example, fibrates, are members of the fatty acid-activated nuclear receptor superfamily that play important roles in lipid and glucose metabolism and have been implicated in obesity-related metabolic diseases such as hyperlipidemia, insulin resistance, and coronary artery disease. In general, fibrates are effective in reducing elevated plasma triglycerides and cholesterol and act as PPAR agonists. The most pronounced effect of fibrates includes a decrease in plasma triglyceride-rich lipoproteins (TRLs). LDL-C levels generally decrease in individuals with elevated baseline plasma concentrations, and HDL cholesterol (HDL-C) levels generally increase when baseline plasma concentrations are low. Non-limiting examples of commonly prescribed fibrates include bezafibrate, gemfibrozil, and fenofibrate.

[0143] Cholesteryl ester transfer protein (CETP) inhibitors play an important role in atherogenesis by reducing the accumulation of cholesteryl esters in macrophages and the arterial wall, thereby reducing foam cell formation and affecting cholesterol absorption. The most promising CETP inhibitor currently known is avisimib.

[0144] ApoA-1 Milano is normally used as a recombinant complex with phospholipid (ETC-216) and produces a regression Petition 870250103709, dated 12 / 11 / 2025, pp. 78 / 179 71 / 170 significant coronary atherosclerosis.

[0145] Non-limiting examples of nonsteroidal anti-inflammatory drugs include oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam and CP-14304; salicylates, such as aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal and fendosal; acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, thiopinac, zidomethacin, acematization, fentiazac, zomepirac, clindac, oxepinac, felbinac and ketorolac; fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic and tolfenamic acids; Propionic acid derivatives, such as ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofen; pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone, azapropazone, and trimetazone.

[0146] Non-limiting examples of steroidal anti-inflammatory drugs include, without limitation, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, clobetasol valerate, desonide, desoximetasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluchlorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortin butyl esters, fluocortolone, fluprednidene acetate (fluprednilidene), flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and the balance of their esters,chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, diflurprednate, fluchloronide, flunisolide, fluorometalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, Petition 870250103709, dated 12 / 11 / 2025, pp. 79 / 179 72 / 170 triamcinolone and mixtures thereof.

[0147] Non-limiting examples of analgesics (pain relievers) include aspirin and other salicylates (such as choline or magnesium salicylate), ibuprofen, ketoprofen, naproxen sodium, and acetaminophen.

[0148] Growth factors are hormones that have various functions, including regulating the production of adhesion molecules, altering cell proliferation, increasing vascularization, increasing collagen synthesis, regulating bone metabolism, and altering cell migration to a specific area. Non-limiting examples of growth factors include insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β), a bone morphogenetic protein (BMP), and the like.

[0149] Non-limiting examples of antiproliferative agents include an alkylating agent, such as nitrogen mustard, ethyleneimine and methylmelamine, alkyl sulfonate, nitrosourea and triazene; an antimetabolite, such as a folic acid analogue, a pyrimidine analogue and a purine analogue; a natural product, such as a vinca alkaloid, an epipodophyllotoxin, an antibiotic, an enzyme, a taxane and a biological response modifier, miscellaneous agents, such as a platinum coordination complex, an anthracenedione, an anthracycline, a substituted urea, a methylhydrazine derivative or an adrenocortical suppressor; or a hormone or antagonist, such as an adrenocorticosteroid, a progestin, an estrogen, an antiestrogen, an androgen, an antiandrogen or a gonadotropin-releasing hormone analogue.Specific examples of chemotherapeutic agents include, for example, nitrogen mustard, epipodophyllotoxin, antibiotic, platinum coordination complex, bleomycin, doxorubicin, paclitaxel, etoposide, 4-OH cyclophosphamide, and cisplatin.

[0150] The HSP family is composed of approximately 25 proteins distinguished by their molecular weights with highly conserved structures. Almost all humans exhibit cellular and humoral immune responses against microbial heat shock protein 60 (HSP60). Petition 870250103709, dated 12 / 11 / 2025, page 80 / 179 73 / 170 Since there is a high degree of antigenic homology between microbial (bacterial and parasitic) and human HSP60, the "cost" of immunity to microbes may be the danger of cross-reactivity with human HSP60 expressed by endothelial cells of stressed arteries. Genuine autoimmunity against altered autologous HSP60 may also trigger this process (Wick et al., TRENDS in Immunology. 2001; 22(12):665-669). HSP has been implicated as a target autoantigen in several experimental autoimmune diseases (arthritis, type I diabetes). Anti-HSP65 and anti-HSP60 antibodies have been shown to be associated with atheromatous lesions in humans. Studies in rabbits and mice show that generating an HSP65-induced immune response through immunization with recombinant protein or with an HSP65-rich preparation of Mycobacterium tuberculosis increases atherogenesis.Since autoimmune processes point to HSP65 as a possible antigenic candidate, creating a non-responsive state through the induction of mucosal “tolerance” has been employed to block these responses. Our group reported that early atherosclerosis was attenuated in mice fed HSP65 compared to mice fed BSA or PBS (Harats et al., J Am Coll Cardiol. 2002; 40:1333-1338), which was further supported by Maron, who demonstrated that nasal vaccination with HSP reduces the inflammatory process associated with atherosclerosis (Maron et al., Circulation. 2002; 106:1708-1715).

[0151] Beta-2-glycoprotein I (beta2GPI) is a phospholipid-binding protein that serves as a target for prothrombotic antiphospholipid antibodies. Recently, it has been shown to provoke an immune-mediated reaction and increase murine atherosclerosis. β antibodies to beta-2-GPI have the ability to activate monocytes and endothelial cells and can induce an immune response to beta2GPI in mice prone to atherosclerosis, accelerating atherosclerosis. When beta2GPI-reactive spleen and lymph node cells were transferred to LDL receptor-deficient mice, they promoted the formation of fatty streaks, demonstrating a direct proatherogenic function for beta2GPI-specific lymphocytes. Induction of tolerance Petition 870250103709, dated 12 / 11 / 2025, page 81 / 179 74 / 170 immunological response to beta2GPI via prior oral feeding with the antigen resulted in a significant reduction in the extent of atherosclerotic lesions. Thus, beta2GPI is a candidate participant in atherosclerotic plaque and may possibly be employed as an immunomodulator of plaque progression. Oral feeding with beta2GPI inhibited the reactivity of lymph node cells to beta2GPI in mice immunized against the human protein. IL-4 and IL-10 production was increased in lymph node cells of beta2GPI-tolerant mice immunized against beta2GPI after preparation with the respective protein. Thus, oral administration of beta2GPI is an effective means of suppressing atherogenesis in mice (George et al., Cardiovasc Res. 2004; 62(3):603-9).

[0152] In certain embodiments, the anti-PC antibodies or pharmaceutical compositions disclosed herein exhibit synergy with the additional therapeutic agent.

[0153] In certain embodiments, the present disclosure refers to an antibody and / or pharmaceutical composition of the present disclosure for use in a method of the present disclosure, wherein the method further comprises the administration of an additional therapeutic agent to the subject. In certain embodiments, the present disclosure refers to (a) an antibody and / or pharmaceutical composition of the present disclosure and (b) an additional therapeutic agent for use as a medicament. In certain embodiments, the present disclosure refers to (a) an antibody and / or pharmaceutical composition of the present disclosure, and (b) an additional therapeutic agent for use in a method for the treatment of an inflammatory disorder. In a further embodiment, the present disclosure refers to a pharmaceutical composition, kit or kit of parts comprising (a) an antibody and / or pharmaceutical composition of the present disclosure and (b) an additional therapeutic agent.In certain modalities, the additional therapeutic agent is an HMG-CoA reductase inhibitor (statin), immunosuppressant, ezetimibe, peroxisome, nicotinic acid, squalene inhibitor, proliferation-activated receptor agonist (PPAR), cholesteryl ester transfer protein (CETP) inhibitor, ApoA-1 Milano, nonsteroidal anti-inflammatory drug, steroidal anti-inflammatory drug, analgesic, factor. Petition 870250103709, dated 12 / 11 / 2025, page 82 / 179 75 / 170 growth, anti-atherosclerosis, antiproliferative, HSP or Beta-2-glycoprotein-I.

[0154] The anti-PC antibody and the additional therapeutic agent (e.g., HMG-CoA reductase inhibitor (statin), immunosuppressant, ezetimibe, peroxisome, nicotinic acid, squalene inhibitor, proliferation-activated receptor agonist (PPAR), cholesteryl ester transfer protein (CETP) inhibitor, ApoA-1 Milano, nonsteroidal anti-inflammatory, steroidal anti-inflammatory, analgesic, growth factor, anti-atherosclerosis, antiproliferative agent, HSP or Beta-2-glycoprotein-I) may be administered separately, sequentially or simultaneously as separate dosage forms.

[0155] An antibody or pharmaceutical composition described in this document may be administered to a subject by a variety of routes. These include, but are not limited to, parenteral, intranasal, intratracheal, oral, intradermal, topical, intramuscular, intraperitoneal, transdermal, intravenous, intratumoral, conjunctival, intra-arterial, and subcutaneous routes. Pulmonary administration may also be employed, for example, by the use of an inhaler or nebulizer, and formulation with an aerosol agent for use as a spray. In certain embodiments, the antibody or pharmaceutical composition described in this document is administered subcutaneously or intravenously. In certain embodiments, the antibody or pharmaceutical composition described in this document is administered intra-arterially. In certain embodiments, the antibody or pharmaceutical composition described in this document is administered intratumorally.In certain modalities, the antibody or pharmaceutical composition described in this document is administered into a lymph node that drains the tumor.

[0156] The amount of an antibody or compound that will be effective in treating and / or preventing a condition will depend on the nature of the disease and can be determined by standard clinical techniques.

[0157] The precise dose to be used in a composition will also depend on the route of administration and the severity of the infection or disease it causes, and should be decided according to the judgment of Petition 870250103709, dated 12 / 11 / 2025, page 83 / 179 76 / 170 physician and the circumstances of each subject. For example, effective doses may also vary depending on the route of administration, target site, patient's physiological state (including age, body weight and health), whether the patient is human or animal, other medications administered, or whether the treatment is prophylactic or therapeutic. Generally, the patient is a human being, but non-human mammals, including transgenic mammals, may also be treated. Treatment dosages are optimally titrated to optimize safety and efficacy.

[0158] An anti-PC antibody described herein can also be used to analyze OxPL levels in a biological sample using classical immunohistological methods known to those skilled in the art, including immunoassays such as enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, or Western blotting. Suitable antibody assay markers are known in the art and include enzymatic markers such as glucose oxidase; radioisotopes such as iodine (125I,121I), carbon (14C), sulfur (35S), tritium (3H), indium (121In), and technetium (99Tc); luminescent labels such as luminol; and fluorescent markers such as fluorescein and rhodamine, and biotin. These markers can be used to label an antibody described in this document. Alternatively, a second antibody that recognizes an anti-PC antibody described herein can be labeled and used in combination with an anti-PC antibody to detect OxPL levels.Therefore, in certain embodiments, the present disclosure refers to the use of an anti-PC antibody from the present disclosure for in vitro detection of OxPL in a biological sample. In another embodiment, the present disclosure refers to the use of an anti-PC antibody from the disclosure to assess and / or detect OxPL levels in a biological sample in vitro or ex vivo, optionally wherein the anti-PC antibody is conjugated to a detectable radionuclide or marker, and / or carries a marker described herein, and / or wherein an immunohistological method is used.

[0159] Assay for OxPL level is intended to include the qualitative or quantitative measurement or estimation of the OxPL level in a first biological sample, either directly (e.g., determining or estimating the absolute OxPL level) or relatively (e.g., comparing with the OxPL level). Petition 870250103709, dated 12 / 11 / 2025, p. 84 / 179 77 / 170 associated with the disease in a second biological sample). The OxPL level in the first biological sample can be measured or estimated and compared to a standard OxPL level, the standard being obtained, for example, from a second biological sample obtained from an individual who does not have the disorder or being determined by the average levels of a population of individuals who do not have the disorder. As will be appreciated in the technique, once the “standard” OxPL level is known, it can be used repeatedly as a standard for comparison. Therefore, in a further embodiment, the present disclosure relates to an in vitro method for testing and / or detecting OxPL protein levels, for example, human OxPL levels, in a biological sample, comprising qualitatively or quantitatively measuring or estimating the OxPL protein level, for example, human OxPL protein, in a biological sample, by an immunohistological method.

[0160] As used herein, the term “biological sample” refers to any biological sample obtained from a subject, cell line, tissue, or other source of cells potentially containing oxidized phospholipids. Methods for obtaining biopsies of tissues and body fluids from animals (e.g., humans or cynomolgus monkeys) are well known in the art. Biological samples include peripheral blood mononuclear cells (PBMCs).

[0161] An anti-PC antibody described in this document can be used for prognostic, diagnostic, monitoring, and screening applications, including well-known and standard in vitro and in vivo applications for the skilled craftsman and based on the present description. Prognostic, diagnostic, monitoring, and screening assays and kits for in vitro assessment and evaluation of immune system status and / or immune response can be used to predict, diagnose, and monitor to evaluate patient samples, including those known or suspected to have immune system dysfunction or in relation to an anticipated or desired immune system response to an antigen. Assessment and evaluation of immune system status and / or immune response are also useful in determining a patient's suitability for a clinical trial of a drug or for the administration of a therapeutic agent or a Petition 870250103709, dated 12 / 11 / 2025, page 85 / 17978 / 170 antibody, including combinations thereof, versus a different agent or antibody. In vivo applications include targeted cell therapy, immune system modulation, and radioimaging of immune responses. Therefore, in certain embodiments, the present disclosure refers to an anti-PC antibody and / or pharmaceutical composition of the present disclosure for use as a diagnostic tool. In certain embodiments, the present disclosure refers to an anti-PC antibody and / or pharmaceutical composition of the present disclosure for use in a method for predicting, diagnosing, and / or monitoring a subject who has or is suspected of having an immune system dysfunction and / or in relation to an anticipated or desired immune system response or antigenic response.In another embodiment, the present disclosure refers to the use of an anti-PC antibody from the disclosure, to predict, diagnose and / or monitor a subject who has or is suspected of having an immune system dysfunction and / or with respect to an anticipated or desired immune system response or antigenic response, by means of analysis and / or detection of human OxPL levels in a biological sample from the subject in vitro or in vivo.

[0162] In certain embodiments, an anti-PC antibody can be used in the immunohistochemistry of biopsy samples. In certain embodiments, the method is an in vitro method. In another embodiment, an anti-PC antibody can be used to detect OxPL levels, or levels of cells containing OxPL, whose levels can then be associated with certain disease symptoms. The anti-PC antibodies described herein may contain a detectable or functional marker and / or perhaps be conjugated to a radionuclide or detectable marker. When fluorescence markers are used, currently available microscopy and fluorescence-activated cell sorting analysis (FACS) or a combination of both procedures of methods known in the art can be used to identify and quantify specific binding members. The anti-PC antibodies described herein may carry or may be conjugated to a fluorescence marker.Exemplary fluorescence markers include, for example, reactive and conjugated probes, such as aminocoumarin, fluorescein, and Texas red dyes. Petition 870250103709, dated 12 / 11 / 2025, page 86 / 179 79 / 170 Alexa Fluor, Cy dyes, and DyLight dyes. An anti-PC antibody may carry or be conjugated to a radioactive tracer or radionuclide, such as the isotopes 3H, 14C, 32P, 35S, 36Cl, 51Cr, 57Co, 58Co, 59Fe, 67Cu, 90Y, 99Tc, 111In, 117Lu, 121I, 124I, 125I, 131I, 198Au, 211At, 213Bi, 225Ac, and 186Re. When radioactive labels are used, currently available and known counting procedures in the art can be used to identify and quantify the specific binding of an anti-PC antibody to PC. In cases where the marker is an enzyme, detection can be performed by any of the colorimetric, spectrophotometric, fluorospectrophotometric, amperometric, or gasometric techniques currently used and known in the art. This can be achieved by contacting a sample or a control sample with an anti-PC antibody under conditions that allow the formation of a complex between the anti-PC antibody and PC.All complexes formed between the anti-PC antibody and PC are detected and compared in the sample and control. Given the specific binding of the anti-PC antibodies described herein to PC, the anti-PC antibodies can be used to specifically detect PC. The anti-PC antibodies described in this document can also be used to purify PC by means of immunoaffinity purification. Also included herein is an assay system that can be prepared in the form of a test kit, kit, or parts kit for the quantitative analysis of the extent of the presence of, for example, PC / PC ligand complexes. The system, test kit, kit, or parts kit may comprise a labeled component, for example, a labeled antibody, and one or more additional immunochemical reagents. POLYNUCLEOTIDES, VECTORS AND METHODS OF ANTIBODY PRODUCTION

[0163] In another aspect, polynucleotides comprising a nucleotide sequence encoding an antibody, or a portion thereof, described herein, or a fragment thereof (e.g., a VL and / or VH; and a light chain and / or heavy chain) that binds specifically to a PC antigen, and vectors, for example, vectors comprising such polynucleotides for recombinant expression in host cells (e.g., E. coli and cells) are provided herein. Petition 870250103709, dated 12 / 11 / 2025, page 87 / 179 80 / 170 of mammals). This document provides polynucleotides comprising nucleotide sequences encoding a heavy and / or light chain of any of the antibodies provided herein, as well as vectors comprising such polynucleotide sequences, for example, expression vectors for their efficient expression in host cells, for example, mammalian cells.

[0164] As used in this document, an “isolated” polynucleotide or nucleic acid molecule is one that is separated from other nucleic acid molecules that are present in the natural source (e.g., in a mouse or a human) of the nucleic acid molecule. Furthermore, an “isolated” nucleic acid molecule, such as a cDNA molecule, may be substantially free of other cellular material or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. For example, the term “substantially free” includes preparations of polynucleotides or nucleic acid molecules with less than about 15%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (in particular less than about 10%) of other material, for example, cellular material, culture medium, other nucleic acid molecules, chemical precursors, and / or other chemicals.In one specific embodiment, one or more nucleic acid molecules encoding an antibody described in this document are isolated or purified.

[0165] In particular aspects, polynucleotides comprising antibody-coding nucleotide sequences that bind specifically to PC and comprise an amino acid sequence as described herein are provided herein, as well as antibodies that compete with such antibodies for binding to PC (e.g., in a dose-dependent manner), or that bind to the same epitope as such antibodies.

[0166] In certain respects, polynucleotides comprising a nucleotide sequence encoding either the light chain or the heavy chain of the antibody described in this document are provided herein. The polynucleotides may comprise nucleotide sequences encoding a Petition 870250103709, dated 12 / 11 / 2025, page 88 / 179 81 / 170 light chain comprising the FRs and CDRs of VL antibodies described in this document (see, for example, Table 1) or nucleotide sequences encoding a heavy chain comprising the FRs and CDRs of VH antibodies described in this document (see, for example, Table 1). In certain embodiments, a polynucleotide encodes a VH, VL, heavy chain and / or light chain of one described in this document. In another embodiment, a polynucleotide encodes the first VH and the first VL of one described in this document. In another embodiment, a polynucleotide encodes the second VH and the second VL of one described in this document. In another embodiment, a polynucleotide encodes the first heavy chain and the first light chain of one described in this document. In another embodiment, a polynucleotide encodes the second heavy chain and the second light chain of one described in this document.In another embodiment, a polynucleotide encodes the VH and / or VL, or the heavy chain and / or the light chain, of an antibody described in this document.

[0167] Also provided here are polynucleotides encoding an anti-PC antibody that are optimized, for example, by codon / RNA optimization, substitution with heterologous signal sequences, and elimination of mRNA instability elements. Methods for generating optimized nucleic acids encoding an anti-PC antibody or a fragment thereof (e.g., light chain, heavy chain, VH domain, or VL domain) for recombinant expression by introducing codon changes and / or eliminating inhibitory regions in mRNA can be carried out by adapting the optimization methods described, for example, in U.S. Patents Nos. 5,965,726; 6,174,666; 6,291,664; 6,414,132; and 6,794,498, consequently, all of which are incorporated herein by reference in their entirety.For example, potential splice sites and instability elements (e.g., A / T-rich or A / U-rich elements) within RNA can be mutated without altering the amino acids encoded by the nucleic acid sequences to increase RNA stability for recombinant expression. The changes utilize degeneracy of the genetic code, for example, using an alternative codon for an identical amino acid. In certain embodiments, it may be desirable to alter one. Petition 870250103709, dated 12 / 11 / 2025, p. 89 / 179 82 / 170 or more codons to encode a conservative mutation, for example, a similar amino acid with chemical structure and properties and / or function similar to the original amino acid. Such methods can increase the expression of an anti-PC antibody or fragment thereof by at least 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or 100-fold or more compared to the expression of an anti-PC antibody encoded by non-optimized polynucleotides.

[0168] In certain embodiments, an optimized polynucleotide sequence encoding an anti-PC antibody described herein or a fragment thereof (e.g., VL domain and / or VH domain) may hybridize with an antisense polynucleotide (e.g., complementary) of a non-optimized polynucleotide sequence encoding an anti-PC antibody described herein or a fragment thereof (e.g., VL domain and / or VH domain). In specific embodiments, an optimized nucleotide sequence encoding an anti-PC antibody described herein or a fragment thereof hybridizes under high stringency conditions with an antisense polynucleotide of a non-optimized polynucleotide sequence encoding an anti-PC antibody described herein or a fragment thereof.In a specific embodiment, an optimized nucleotide sequence encoding an anti-PC antibody described herein or a fragment thereof hybridizes under high-stringency, intermediate, or low-stringency hybridization conditions with an antisense polynucleotide of a non-optimized nucleotide sequence encoding an anti-PC antibody described herein or a fragment thereof. Information on hybridization conditions has been described; see, for example, U.S. Patent Application Publication No. 2005 / 0048549 (e.g., paragraphs 72-73), which is incorporated herein by reference in its entirety.

[0169] Polynucleotides can be obtained, and the nucleotide sequence of the polynucleotides determined, by any method known in the art. Nucleotide sequences encoding antibodies described in this document, for example, antibodies described in Table 1, and modified versions of these antibodies can be determined using well-established methods. Petition 870250103709, dated 12 / 11 / 2025, page 90 / 179 83 / 170 known in the art, that is, nucleotide codons known to encode specific amino acids, are assembled in such a way as to generate a nucleic acid that encodes the antibody. Such an antibody-encoding polynucleotide can be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier G et al., (1994), BioTechniques 17: 242 to 246, here incorporated by reference in its entirety), which, in short, involves the synthesis of overlapping oligonucleotides containing portions of the antibody-encoding sequence, the pairing and ligation of these oligonucleotides, and then the amplification of the linked oligonucleotides by PCR.

[0170] Alternatively, a polynucleotide encoding an antigen-binding region described herein or an antibody described in this document may be generated from nucleic acid from a suitable source (e.g., a hybridoma) using methods well known in the art (e.g., PCR and other molecular cloning methods). For example, PCR amplification using hybridizable synthetic primers with the 3' and 5' ends of a known sequence may be performed using genomic DNA obtained from hybridoma cells producing the antibody of interest. Such PCR amplification methods may be used to obtain nucleic acids comprising the sequence encoding the light chain and / or heavy chain of an antibody. Such PCR amplification methods may be used to obtain nucleic acids comprising the sequence encoding the variable region of the light chain and / or the variable region of the heavy chain of an antibody.The amplified nucleic acids can be cloned into vectors for expression in host cells and for subsequent cloning.

[0171] If a clone containing a nucleic acid encoding a specific antigen- or antibody-binding region is not available, but the sequence of the antigen-binding region or antibody molecule is known, a nucleic acid encoding the immunoglobulin may be chemically synthesized or obtained from a suitable source (e.g., an antibody cDNA library or a cDNA library generated from, or Petition 870250103709, dated 12 / 11 / 2025, page 91 / 179 84 / 170 nucleic acid, preferably poly A+ RNA, isolated from any tissue or cells expressing the antibody, such as hybridoma cells selected to express an antibody described in this document) by PCR amplification using hybridizable synthetic primers with the 3' and 5' ends of the sequence, or by cloning using a specific oligonucleotide probe for the specific genetic sequence to identify, for example, a cDNA clone from a cDNA library encoding the antibody. Amplified nucleic acids generated by PCR can then be cloned into replicable cloning vectors using any method well known in the art.

[0172] The DNA encoding the anti-PC antibodies described herein can be easily isolated and sequenced using conventional procedures (e.g., using oligonucleotide probes that are capable of specifically binding to the genes encoding the heavy and light chains of the anti-PC antibodies). Hybridoma cells can serve as a source of this DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells, such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells (e.g., CHO GS System™ (Lonza) CHO cells), or myeloma cells that otherwise do not produce immunoglobulin protein, to achieve the synthesis of recombinant anti-PC antibodies in host cells.

[0173] To generate complete antibodies or antigen-binding regions, PCR primers including VH or VL nucleotide sequences, a restriction site, and a flanking sequence to protect the restriction site can be used to amplify the VH or VL sequences into scFv clones. Using cloning techniques known to those skilled in the art, PCR-amplified VH domains can be cloned into vectors expressing a heavy chain constant region, for example, the human gamma 1 or human gamma 4 constant region, and PCR-amplified VL domains can be cloned into vectors expressing a light chain constant region, for example, human kappa or lambda constant regions. In certain embodiments, the Petition 870250103709, dated 12 / 11 / 2025, page 92 / 179 85 / 170 vectors for expressing VH or VL domains comprise an EF-Iα promoter, a secretion signal, a cloning site for the variable region, constant regions, and a selection marker such as neomycin. The VH and VL domains can also be cloned into a vector expressing the necessary constant regions. The heavy chain conversion vectors and light chain conversion vectors are then co-transfected into cell lines to generate stable or transient cell lines expressing full-length antibodies, e.g., IgG, using techniques known to those skilled in the art.

[0174] DNA can also be modified, for example, by replacing the coding sequence with the constant regions of the human heavy and light chain in place of the murine sequences, or by covalently linking all or part of the coding sequence to the immunoglobulin coding sequence for a non-immunoglobulin polypeptide.

[0175] Polynucleotides are also provided that hybridize under high-rigor, intermediate-rigor, or low-rigor hybridization conditions with polynucleotides encoding an antibody described in this document. In specific embodiments, the polynucleotides described herein hybridize under high-rigor, intermediate-rigor, or low-rigor hybridization conditions with polynucleotides encoding a VH domain and / or VL domain provided in this document.

[0176] The hybridization conditions have been described in the art and are known to one skilled in the art. For example, hybridization under stringent conditions may involve filter-bound DNA hybridization in 6x sodium chloride / sodium citrate (SSC) at about 45 °C followed by one or more washes in 0.2xSSC / 0.1% SDS at about 50 to 65 °C; hybridization under highly stringent conditions may involve filter-bound nucleic acid hybridization in 6xSSC at about 45 °C followed by one or more washes in 0.1xSSC / 0.2% SDS at about 68 °C. Hybridization under other stringent hybridization conditions is known to those skilled in the art and has been described, see, for example, Ausubel FM et al., eds., (1989) Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc. and John Wiley & Sons, Inc., New York, pages 6.3.1-6.3.6 and Petition 870250103709, dated 12 / 11 / 2025, p. 93 / 179 86 / 170 2.10.3, which is incorporated herein by reference in its entirety.

[0177] In certain aspects, cells (e.g., host cells) expressing (e.g., recombinantly) antibodies described herein that specifically bind to PC, and related expression polynucleotides and vectors are provided herein. Vectors (e.g., expression vectors) comprising polynucleotides containing nucleotide sequences encoding anti-PC antibodies or a fragment for recombinant expression in host cells, preferably mammalian cells (e.g., CHO cells), are provided herein. Host cells comprising such vectors for recombinantly expressing anti-PC antibodies described herein (e.g., human or humanized antibody) are also provided herein. In a particular aspect, methods for producing an antibody described herein are provided herein, comprising expressing the antibody from a host cell.

[0178] Recombinant expression of an antibody described herein (e.g., a full-length antigen-binding region or antibody or heavy and / or light chain of an antibody described herein) that specifically binds to PC generally involves constructing an expression vector containing a polynucleotide encoding the antibody. Once a polynucleotide encoding an antibody molecule, heavy and / or light chain of an antibody, or a fragment thereof (e.g., variable regions of heavy and / or light chain) described in this document is obtained, the vector for producing the antibody molecule can be produced by recombinant DNA technology using techniques well known in the art. Thus, methods for preparing a protein expressing a polynucleotide containing an antibody or antibody fragment (e.g., light chain or heavy chain) encoding the nucleotide sequence are described in this document.Methods that are well known to those skilled in the art can be used to construct expression vectors containing an antibody or antibody fragment (e.g., light chain or heavy chain), coding sequences, and appropriate transcription and translation control signals. These methods include, for example, in vitro recombinant DNA techniques. Petition 870250103709, dated 12 / 11 / 2025, page 94 / 179 87 / 170 synthetic and in vivo genetic recombination. Replicable vectors are also provided comprising a nucleotide sequence encoding an antibody molecule described in this document, a heavy or light chain of an antibody, a variable region of a heavy or light chain of an antibody or a fragment thereof, or a CDR of a heavy or light chain, operationally linked to a promoter. Such vectors may, for example, include the nucleotide sequence encoding the constant region of the antibody molecule (see, for example, International Publications Nos. WO 86 / 05807 and WO 89 / 01036; and US Patent No. 5,122,464, which are incorporated herein by reference in their entirety) and variable regions of the antibody may be cloned into such a vector for expression of the entire heavy chain, the entire light chain, or both heavy and light chains.

[0179] In certain embodiments, a vector comprises a polynucleotide encoding a VH, VL, heavy chain and / or light chain of an antibody described in this document. In another embodiment, a vector comprises a polynucleotide encoding the VH and VL of an antibody described in this document. In yet another embodiment, a vector comprises a polynucleotide encoding the heavy chain and light chain of an antibody described in this document.

[0180] An expression vector can be transferred into a cell (e.g., host cell) by conventional techniques and the resulting cells can then be cultured by conventional techniques to produce cells containing an antibody described in this document or a fragment thereof. Thus, host cells containing a polynucleotide encoding an antibody described in this document or fragments thereof, or a heavy or light chain thereof, or a fragment thereof, or a single-chain antibody described herein, operationally linked to a promoter for expression of such sequences in the host cell, are provided herein.

[0181] In another embodiment, a host cell comprises a polynucleotide encoding the VH and VL of an antibody described herein. In another embodiment, a host cell comprises a vector comprising a polynucleotide encoding the VH and VL of an antibody described herein. Petition 870250103709, dated 12 / 11 / 2025, page 95 / 179 88 / 170 in this document. In another embodiment, a host cell comprises a first polynucleotide encoding the VH of an antibody described herein, and a second polynucleotide encoding the VL of an antibody described in this document. In another embodiment, a host cell comprises a first vector comprising a first polynucleotide encoding the VH of an antibody described in this document and a second vector comprising a second polynucleotide encoding the VL of an antibody described in this document.

[0182] In specific embodiments, a variable heavy chain / heavy chain region expressed by a first cell is associated with a variable light chain / light chain region of a second cell to form an anti-PC antibody described herein. In certain embodiments, a host cell population comprising such a first host cell and such a second host cell is provided in this document.

[0183] In certain embodiments, a population of vectors is provided herein comprising a first vector comprising a polynucleotide encoding a light chain / variable region of the light chain of an anti-PC antibody described herein, and a second vector comprising a polynucleotide encoding a heavy chain / variable region of the heavy chain of an anti-PC antibody described herein.

[0184] A variety of host expression vector systems can be used to express antibody molecules described herein (see, for example, U.S. Patent No. 5,807,715, which is incorporated herein by reference in its entirety). Such host expression systems represent vehicles by which the coding sequences of interest can be produced and subsequently purified, but also represent cells that can, when transformed or transfected with the appropriate nucleotide coding sequences, express an antibody molecule described herein in situ. These include, but are not limited to, microorganisms such as bacteria (e.g., E. coli and B. subtilis) transformed with, for example, recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors. Petition 870250103709, dated 12 / 11 / 2025, page 96 / 179 89 / 170 containing antibody-coding sequences; yeast (e.g., Saccharomyces and Pichia) transformed with, for example, recombinant yeast expression vectors containing antibody-coding sequences; insect cell systems infected with, for example, recombinant virus expression vectors (e.g., baculovirus) containing antibody-coding sequences; plant cell systems (e.g., green algae such as Chlamydomonas reinhardtii) infected with, for example, recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with, for example, recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody-coding sequences; or mammalian cell systems (e.g., COS cells (e.g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6, VERO, CRL7O3O, HsS78Bst, HeLa and NIH 3T3, HEK-293T, HepG2, SP210, R1.1, BW, LM, BSC1, BSC40, YB / 20 and BMT10) harboring, for example, recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or mammalian viruses (e.g., adenovirus late promoter; vaccinia virus 7.5K promoter). In one specific embodiment, the antibody-expressing cells described in this document are Chinese hamster ovary (CHO) cells, for example, CHO GS System™ (Lonza) CHO cells. In certain embodiments, the heavy chain and / or light chain of an antibody produced by a CHO cell may have an N-terminal glutamine or glutamate residue substituted with pyroglutamate. In certain embodiments, the antibody-expressing cells described in this document are human cells, for example, human cell lines.In one specific embodiment, a mammalian expression vector is pOptiVEC™ or pcDNA3.3. In certain embodiments, bacterial cells, such as Escherichia coli, or eukaryotic cells (e.g., mammalian cells), especially for the expression of a whole recombinant antibody molecule, are used for the expression of a recombinant antibody molecule. For example, mammalian cells, such as CHO cells, in conjunction with a vector, such as the main intermediate promoter element of the gene. Petition 870250103709, dated 12 / 11 / 2025, page 97 / 179 Early human cytomegalovirus 90 / 170 cells are an effective expression system for antibodies (Foecking MK & Hofstetter H (1986) Gene 45: 101 to 105; and Cockett MI et al., (1990) Biotechnology 8(7): 662 to 667, each of which is incorporated herein by reference in its entirety). In certain embodiments, the antibodies described herein are produced by CHO cells or NS0 cells. In one specific embodiment, the expression of antibody-encoding nucleotide sequences described herein that bind specifically to PC is regulated by a constitutive promoter, inducible promoter, or tissue-specific promoter.

[0185] In bacterial systems, several expression vectors can be advantageously selected depending on the intended use for the antibody molecule being expressed. For example, when a large quantity of such an antibody must be produced, for the generation of pharmaceutical compositions of an antibody molecule, vectors that direct the expression of high levels of fusion protein products that are easily purified may be desirable. Such vectors include, but are not limited to, the E. expression vector.coli pUR278 (Ruether U & Mueller-Hill B (1983) EMBO J 2: 1791 to 1794), in which the coding sequence can be individually linked to the vector in a frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye S & Inouye M (1985) Nuc Acids Res 13: 3101 to 3109; Van Heeke G & Schuster SM (1989) J Biol Chem 24: 5503-5509); and similar vectors, all of which are incorporated herein by reference in their entirety. For example, pGEX vectors can also be used to express foreign polypeptides as fusion proteins with glutathione 5-transferase (GST). In general, these fusion proteins are soluble and can be easily purified from lysed cells by adsorption and binding to glutathione agarose beads of the matrix, followed by elution in the presence of free glutathione.pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites, so that the product of the cloned target gene can be released from the GST chemical portion.

[0186] In an insect system, the nuclear polyhedrosis virus of Autographa californica (AcNPV), for example, can be used as Petition 870250103709, dated 12 / 11 / 2025, page 98 / 179 91 / 170 vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The coding sequence can be individually cloned into non-essential regions (e.g., the polyhedrin gene) of the virus and placed under the control of an AcNPV promoter (e.g., the polyhedrin promoter).

[0187] In mammalian host cells, several virus-based expression systems can be used. In cases where an adenovirus is used as an expression vector, the coding sequence of interest can be ligated to an adenovirus transcription / translation control complex, for example, the late promoter and the tripartite leader sequence. This chimeric gene can then be inserted into the adenovirus genome by in vitro or in vivo recombination. Insertion into a non-essential region of the viral genome (e.g., El or E3 region) will result in a viable recombinant virus capable of expressing the molecule in infected hosts (see, for example, Logan J & Shenk T, (1984) PNAS 81(12): 3655-9, which is incorporated herein by reference in its entirety). Specific initiation signals may also be required for efficient translation of inserted coding sequences. These signals include the ATG initiation codon and adjacent sequences.Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of various origins, both natural and synthetic. The efficiency of expression can be increased by the inclusion of appropriate transcription enhancers, transcription terminators, etc. (see, for example, Bitter G et al., (1987) Methods Enzymol. 153: 516 to 544, which is incorporated here by reference in its entirety).

[0188] In addition, a host cell strain can be chosen that modulates the expression of the inserted sequences or modifies and processes the gene product in the specific desired way. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products can be important for protein function. Different host cells have characteristic and specific mechanisms for processing. Petition 870250103709, dated 12 / 11 / 2025, page 99 / 179 92 / 170 post-translational and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the expressed foreign protein. For this purpose, eukaryotic host cells that possess the cellular machinery for the proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product can be used. These mammalian host cells include, but are not limited to, CHO, VERO, BHK, Hela, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT2O and T47D cells, NS0 (a murine myeloma cell line that does not endogenously produce any immunoglobulin chain), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, BW, LM, BSC1, BSC40, YB / 20, BMT10 and HsS78Bst cells. In certain embodiments, the anti-PC antibodies described herein are produced in mammalian cells, such as CHO cells.

[0189] In a specific embodiment, the antibodies described in this document have reduced fucose content or no fucose content. Such antibodies can be produced using techniques known to one skilled in the art. For example, the antibodies can be expressed in cells deficient in or unable to fucosylate. In a specific example, cell lines with knockout of both alleles of α1,6-fucosyltransferase can be used to produce antibodies with reduced fucose content. The Potelligent® system (Lonza) is an example of a system that can be used to produce antibodies with reduced fucose content.

[0190] For high-throughput and long-term recombinant protein production, stable expression cells can be generated. For example, cell lines that stably express an anti-PC antibody described herein can be engineered. In specific embodiments, a cell provided in this document stably expresses a light chain / variable light chain region and a heavy chain / variable heavy chain region that associate to form an antigen-binding region or an antibody described in this document. Petition 870250103709, dated 12 / 11 / 2025, pp. 100 / 179 93 / 170

[0191] In certain respects, instead of using expression vectors containing viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.) and a selectable marker. After the introduction of the foreign DNA / polynucleotide, the genetically modified cells can grow for 1-2 days in enriched media and then are switched to a selective medium. The selectable marker on the recombinant plasmid confers resistance to selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci that, in turn, can be cloned and expanded into cell lines. This method can be used advantageously to manipulate cell lines expressing an anti-PC described in this document or a fragment thereof.These genetically modified cell lines can be particularly useful in screening and evaluating compositions that interact directly or indirectly with the antibody molecule.

[0192] Several selection systems can be used, including, but not limited to, herpes simplex virus thymidine kinase (Wigler M et al., (1977) Cell 11(1): 223-32), hypoxanthine-guanine phosphoribosyltransferase (Szybalska EH & Szybalski W (1962) PNAS 48(12): 2026-2034) and adenine phosphoribosyltransferase genes (Lowy I et al., (1980) Cell 22(3): 817-23) in tk, hgprt or aprt cells, respectively, all of which are hereby incorporated by reference in their entirety. Furthermore, antimetabolite resistance can be used as a basis for selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler M et al., (1980) PNAS 77(6): 3567 to 3570; O'Hare K et al., (1981) PNAS 78: 1527-31); gpt, which confers resistance to mycophenolic acid (Mulligan RC & Berg P (1981) PNAS 78(4): 2072 to 2076); neo, which confers resistance to the aminoglycoside G-418 (Wu GY & Wu CH (1991) Biotherapy 3: 87-95; Tolstoshev P (1993) Ann Rev Pharmacol Toxicol 32: 573-596; Mulligan RC (1993) Science 260: 926 to 932; and Morgan RA & Anderson WF (1993) Ann Rev Biochem 62: 191 to 217; Nabel GJ & Felgner PL (1993) Trends Biotechnol 11(5): 211 to 215); and hygro, which confers resistance to hygromycin (Santerre. Petition 870250103709, dated 12 / 11 / 2025, pp. 101 / 179 94 / 170 RF et al., (1984) Gene 30(1-3): 147 to 156), all of which are incorporated herein by reference in their entirety. Methods commonly known in recombinant DNA technology can be routinely applied to select the desired recombinant clone and such methods are described, for example, in Ausubel FM et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, NY (1993); Kriegler M, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990); and in Chapters 12 and 13, Dracopoli NC et al., (eds.), Current Protocols in Human Genetics, John Wiley & Sons, NY (1994); Colbère-Garapin F et al., (1981) J Mol Biol 150: 1-14, all of which are incorporated herein by reference in their entirety.

[0193] The expression levels of an antibody molecule can be increased by vector amplification (for a review, see Bebbington CR & Hentschel CCG, The use of vectors based on gene amplification for the expression of cloned genes in mammalian cells in DNA cloning, Vol. 3 (Academic Press, New York, 1987), which is incorporated herein by reference in its entirety). When a marker in the vector system is amplifiable, increasing the level of inhibitor present in the host cell culture will increase the number of copies of the marker gene. As the amplified region is associated with the gene of interest, protein production will also increase (Crouse GF et al., (1983) Mol Cell Biol 3: 257 to 266, which is incorporated herein by reference in its entirety).

[0194] The host cell can be cotransfected with two or more expression vectors described in this document, the first vector encoding a heavy chain-derived polypeptide and the second vector encoding a light chain-derived polypeptide. The two vectors can contain identical selectable markers that allow equal expression of heavy and light chain polypeptides. Host cells can be cotransfected with different amounts of two or more expression vectors. For example, host cells can be transfected with any of the following ratios of a first expression vector and a second expression vector: approximately 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:12, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45 Petition 870250103709, dated 12 / 11 / 2025, page 102 / 179 95 / 170 or 1:50.

[0195] Alternatively, a single vector that encodes and is capable of expressing both heavy and light chain polypeptides may be used. In such situations, the light chain should be positioned before the heavy chain to avoid an excess of free and toxic heavy chain (Proudfoot NJ (1986) Nature 322: 562-565; and Kohler G (1980) PNAS 77: 2197-2199, each of which is incorporated herein by reference in its entirety). The coding sequences for the heavy and light chains may comprise cDNA or genomic DNA. The expression vector may be monocistronic or multicistronic. A multicistronic nucleic acid construct can encode 2, 3, 4, 5, 6, 7, 8, 9, 10 or more genes / nucleotide sequences, or in the range of 2-5, 5-10 or 10-20 genes / nucleotide sequences.For example, a bicistronic nucleic acid construct might comprise, in the following order, a promoter, a first gene (e.g., the heavy chain of an antibody described in this document), and a second gene (e.g., the light chain of an antibody described in this document). In such an expression vector, transcription of both genes can be driven by the promoter, while mRNA translation of the first gene can be by a cap-dependent scanning mechanism, and mRNA translation of the second gene can be by a cap-independent mechanism, e.g., by an IRES.

[0196] Once an antibody molecule described herein has been produced by recombinant expression, it can be purified by any method known in the art for the purification of an immunoglobulin molecule, for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for the specific antigen after Protein A and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for protein purification. Furthermore, the antibodies described in this document can be fused with heterologous polypeptide sequences described herein or otherwise known in the art to facilitate purification.

[0197] In specific modalities, an antibody described Petition 870250103709, dated 12 / 11 / 2025, page 103 / 179 96 / 170 in this document is isolated or purified. In certain embodiments, an isolated antibody is one that is substantially free of other antibodies with antigenic specificities different from the isolated antibody. For example, in certain embodiments, a preparation of an antibody described in this document is substantially free of cellular material and / or chemical precursors. The language “substantially free of cellular material” includes preparations of an antibody in which the antibody is separated from the cellular components of the cells from which it is isolated or recombinantly produced.Thus, an antibody that is substantially free of cellular material includes antibody preparations having less than about 30%, 20%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (by dry weight) of heterologous protein (also referred to in this document as a “contaminant protein”) and / or variants of an antibody, for example, different post-translational modified forms of an antibody or other different versions of an antibody (e.g., antibody fragments). When the antibody is produced recombinantly, it is also generally substantially free of culture medium, i.e., the culture medium represents less than about 20%, 10%, 2%, 1%, 0.5%, or 0.1% of the volume of the protein preparation. When the antibody is produced by chemical synthesis, it is generally substantially free of chemical precursors or other chemicals, i.e., it is separated from chemical precursors or other chemicals that are involved in protein synthesis.Consequently, such antibody preparations have less than about 30%, 20%, 10%, or 5% (by dry weight) of chemical precursors or compounds other than the antibody of interest. In one specific embodiment, the antibodies described in this document are isolated or purified.

[0198] Anti-PC antibodies or fragments thereof may be produced by any method known in the art for the synthesis of proteins or antibodies, for example, by chemical synthesis or by recombinant expression techniques. The methods described in this document employ, unless otherwise indicated, conventional techniques in molecular biology, microbiology, genetic analysis, recombinant DNA, organic chemistry, biochemistry, Petition 870250103709, dated 12 / 11 / 2025, page 104 / 179 97 / 170 PCR, oligonucleotide synthesis and modification, nucleic acid hybridization, and related fields within the skill of the technique. These techniques are described, for example, in the references cited in this document and are fully explained in the literature. See, for example, Maniatis T et al., (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press; Sambrook J et al., (1989), Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory Press; Sambrook J et al., (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Ausubel FM et al., Current Protocols in Molecular Biology, John Wiley & Sons (1987 and annual updates); Current Protocols in Immunology, John Wiley & Sons (1987 and annual updates); Gait (ed.) (1984) Oligonucleotide Synthesis: A Practical Approach, IRL Press; Eckstein (ed.) (1991) Oligonucleotides and Analogs: A Practical Approach, IRL Press; Birren B et al., (eds.) (1999) Genome Analysis: A Laboratory Manual, Cold Spring Harbor Laboratory Press, all incorporated herein by reference in their entirety.

[0199] In a specific embodiment, an antibody described in this document is prepared, expressed, created, or isolated by any means involving creation, for example, through synthesis, genetic modification of DNA sequences. In certain embodiments, such an antibody comprises sequences (e.g., DNA sequences or amino acid sequences) that do not naturally exist in the germline antibody repertoire of an animal or mammal (e.g., human) in vivo.

[0200] In one aspect, a method is provided here for producing an anti-PC antibody comprising culturing a cell or host cell described herein. In certain embodiments, the method is performed in vitro. In a certain aspect, a method is provided here for making an anti-PC antibody comprising expressing (e.g., recombinantly expressing) the antibody using a cell or host cell described herein (e.g., a cell or host cell comprising polynucleotides encoding an antibody described herein). In certain embodiments, the cell is a single cell. In certain Petition 870250103709, dated 12 / 11 / 2025, page 105 / 179 In 98 / 170 embodiments, exogenous polynucleotides were introduced into the cell. In certain embodiments, the method also includes the step of purifying the antibody obtained from the host cell or cell.

[0201] In certain embodiments, an antibody is produced by expressing in a cell a polynucleotide encoding the HV and LV of an antibody described in this document under suitable conditions so that the polynucleotides are expressed and the antibody is produced. In another embodiment, an antibody is produced by expressing in a cell a polynucleotide encoding the heavy chain and light chain of an antibody described in this document under suitable conditions so that the polynucleotides are expressed and the antibody is produced. In certain embodiments, an antibody is produced by expressing in a cell a first polynucleotide encoding the HV of an antibody described in this document, and a second polynucleotide encoding the LV of an antibody described in this document, under suitable conditions so that the polynucleotides are expressed and the antibody is produced.In certain embodiments, an antibody is produced by expressing in a cell a first polynucleotide encoding the heavy chain of an antibody described in this document, and a second polynucleotide encoding the light chain of an antibody described in this document, under conditions suitable for the polynucleotides to be expressed and the antibody to be produced.

[0202] Methods for producing polyclonal antibodies are known in the art (see, for example, Chapter 11 in: Short Protocols in Molecular Biology, (2002) 5th Ed., Ausubel FM et al., eds., John Wiley and Sons, New York, which is incorporated herein by reference in its entirety).

[0203] Monoclonal antibodies can be prepared using a wide variety of techniques known in the art, including the use of hybridoma, recombinant, and phage display technologies, or a combination thereof. For example, monoclonal antibodies can be produced using hybridoma techniques, including those known in the art and taught, for example, in Harlow E & Lane D, Antibodies: A Laboratory Manual, (Cold Spring Petition 870250103709, dated 12 / 11 / 2025, pp. 106 / 179 99 / 170 Harbor Laboratory Press, 2nd ed. 1988); Hammerling GJ et al., in: Monoclonal Antibodies and T-Cell Hybridomas 563 681 (Elsevier, NY, 1981), each of which is incorporated herein by reference in its entirety. The term “monoclonal antibody” as used in this document is not limited to antibodies produced by hybridoma technology. For example, monoclonal antibodies may be recombinantly produced from host cells that exogenously express an antibody described in this document or a fragment thereof, for example, the light chain and / or heavy chain of that antibody.

[0204] In specific embodiments, a “monoclonal antibody,” as used herein, is an antibody produced by a single cell (e.g., hybridoma or host cell producing a recombinant antibody), wherein the antibody binds specifically to the PC as determined, for example, by ELISA or other antigen binding or competitive binding assay known in the art, or in the examples provided herein. In certain embodiments, a monoclonal antibody may be a chimeric antibody or a humanized antibody. In certain embodiments, a monoclonal antibody is a monovalent antibody or a multivalent (e.g., bivalent) antibody. In certain embodiments, a monoclonal antibody is a monospecific or multispecific (e.g., bispecific) antibody.The monoclonal antibodies described in this document can, for example, be produced by the hybridoma method, as described in Kohler G & Milstein C (1975) Nature 256: 495, which is incorporated herein by reference in its entirety, or can, for example, be isolated from phage libraries using the techniques described in this document, for example. Other methods for the preparation of clonal cell lines and thus expressed monoclonal antibodies are well known in the art (see, for example, Chapter 11 in: Short Protocols in Molecular Biology, (2002) 5th Ed., Ausubel FM et al., supra).

[0205] As used in this document, an antibody binds to an antigen in a multivalent (e.g., bivalent) manner when the antibody comprises at least two (e.g., two or more) binding regions. Petition 870250103709, dated 12 / 11 / 2025, pp. 107 / 179 100 / 170 monovalent, each monovalent binding region capable of binding to one epitope on the antigen. Each monovalent binding region can bind to the same or different epitopes on the antigen.

[0206] Methods for producing and screening specific antibodies using hybridoma technology are routine and well-known in the art. For example, in the hybridoma method, a mouse or other suitable host animal, such as a sheep, goat, rabbit, rat, hamster, or monkey, is immunized to produce lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein (e.g., PC) used for immunization. Alternatively, lymphocytes can be immunized in vitro. The lymphocytes are then fused with myeloma cells using a suitable fusion agent, such as polyethylene glycol, to form a hybridoma cell (Goding JW (Ed.), Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986), incorporated here by reference in its entirety). Furthermore, a RIMMS (repetitive multisite immunization) technique can be used to immunize an animal (Kilpatrick KE et al., (1997) Hybridoma 16:381 to 389, incorporated herein by reference in its entirety).

[0207] In certain embodiments, mice (or other animals such as rats, monkeys, donkeys, pigs, sheep, hamsters, or dogs) can be immunized with an antigen (e.g., PC) and, once an immune response is detected, for example, antibodies specific to the antigen are detected in the mouse serum, the mouse spleen is collected and splenocytes are isolated. The splenocytes are then fused by well-known techniques to any suitable myeloma cells, for example, SP20 cell line cells available from the American Type Culture Collection (ATCC®) (Manassas, VA), to form hybridomas. The hybridomas are selected and cloned by limited dilution. In certain embodiments, lymph nodes from immunized mice are collected and fused with NS0 myeloma cells.

[0208] The hybridoma cells thus prepared are seeded and cultured in a suitable culture medium that preferably Petition 870250103709, dated 12 / 11 / 2025, pp. 108 / 179 101 / 170 contains one or more substances that inhibit the growth or survival of unfused parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRT or HPRT), the culture medium for hybridomas will typically include hypoxanthine, aminopterin, and thymidine (HAT medium), substances that prevent the growth of HGPRT-deficient cells.

[0209] Specific modalities employ myeloma cells that fuse efficiently, support stable high-level antibody production by selected antibody-producing cells, and are sensitive to a medium such as HAT medium. Among these myeloma cell lines are murine myeloma cell lines, such as the NS0 cell line or those derived from MOPC-21 and MPC-11 mouse tumors available at the Salk Institute Cell Distribution Center, San Diego, CA, USA, and SP-2 or X63-Ag8653 cells available at the American Type Culture Collection, Rockville, MD, USA. Human myeloma and human-mouse heteromyeloma cell lines have also been described for the production of human monoclonal antibodies (Kozbor D (1984) J Immunol 133: 3001 to 3005; Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987), each of which is incorporated herein by reference in its entirety).

[0210] The culture medium in which hybridoma cells are growing is analyzed for the production of monoclonal antibodies directed against CP. The binding specificity of the monoclonal antibodies produced by the hybridoma cells is determined by methods known in the art, for example, immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA).

[0211] After hybridoma cells that produce antibodies with the desired specificity, affinity, and / or activity have been identified, clones can be subcloned using limiting dilution procedures and cultured using standard methods (Goding JW (Ed.), Monoclonal Antibodies: Principles and Practice, supra). Suitable culture media for this purpose include, for example, Petition 870250103709, dated 12 / 11 / 2025, pp. 109 / 179 102 / 170 example, D-MEM medium or RPMI 1640. In addition, hybridoma cells can be cultured in vivo as ascites tumors in an animal.

[0212] Monoclonal antibodies secreted by subclones are adequately separated from culture medium, ascitic fluid or serum by conventional immunoglobulin purification procedures, such as, for example, protein A-Sepharose, hydroxyapatite chromatography, gel electrophoresis, dialysis or affinity chromatography.

[0213] The antibodies described herein include, for example, antibody fragments that recognize PC and can be generated by any technique known to those skilled in the art. For example, Fab and F(ab')2 fragments described in this document can be produced by proteolytic cleavage of immunoglobulin molecules, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab')2 fragments). A Fab fragment corresponds to one of the two identical arms of an antibody molecule and contains the complete light chain paired with the VH and CH1 domains of the heavy chain. An F(ab')2 fragment contains the two antigen-binding arms of an antibody molecule linked by disulfide bonds in the hinge region.

[0214] In addition, the antibodies described in this document can also be generated using various phage display methods known in the art. In phage display methods, the functional domains of antibodies are displayed on the surface of phage particles carrying the polynucleotide sequences that encode them. In particular, DNA sequences encoding the VH and VL domains are amplified from animal cDNA libraries (e.g., human or murine cDNA libraries from affected tissues). The DNA encoding the VH and VL domains is recombined together with an scFv linker by PCR and cloned into a phage vector. The vector is electroporated into E. coli, and the E. coli is infected with helper phage. The phages used in these methods are typically filamentous phages, including fd and M13, and the VH and VL domains are usually recombinantly fused to gene III or gene VIII of the phage.The phage expresses an antigen-binding region that binds to an antigen. Petition 870250103709, dated 12 / 11 / 2025, pp. 110 / 179 103 / 170 specific can be selected or identified with the antigen, for example, using labeled antigen or antigen bound or captured to a solid surface or sphere. Examples of phage display methods that can be used to produce the antibodies described in this document include those disclosed in Brinkman U et al., (1995) J Immunol Methods 182: 41 to 50; Ames RS et al., (1995) J Immunol Methods 184: 177 to 186; Kettleborough CA et al., (1994) Eur J Immunol 24: 952 to 958; Persic L et al., (1997) Gene 187: 9 to 18; Burton DR & Barbas CF (1994) Advan Immunol 57: 191 to 280; PCT Application No. PCT / GB91 / 001134; International Publications Nos. WO 90 / 02809, WO 91 / 10737, WO 92 / 01047, WO 92 / 18619, WO 93 / 11236, WO 95 / 15982, WO 95 / 20401 and WO 97 / 13844; and US Patents Nos. 5,698,426, 5,223,409, 5,403,484, 5,580,717, 5,427,908, 5,750,753, 5,821,047 5,571,698, 5,427,908, 5,516,637, 5,780,225, 5,658,727, 5,733,743, and 5,969,108, all of which are incorporated herein by reference in their entirety.

[0215] As described in the references above, after phage selection, the antibody-coding regions of the phage can be isolated and used to generate whole antibodies, including human antibodies, or any other desired antigen-binding fragment, and expressed in any desired host, including mammalian cells, insect cells, plant cells, yeast and bacteria, for example, as described below. Techniques for producing recombinant antibody fragments, such as Fab, Fab' and F(ab')2 fragments, can also be employed using methods known in the art, such as those disclosed in PCT Publication No. WO 92 / 22324; Mullinax RL et al., (1992) BioTechniques 12(6): 864 to 869; Sawai H et al., (1995) Am J Reprod Immunol 34: 26 to 34; and Better M et al., (1988) Science 240: 1041 to 1043, all of which are incorporated herein by reference in their entirety.

[0216] In certain embodiments, to generate complete antibodies, PCR primers including VH or VL nucleotide sequences, a restriction site, and a flanking sequence to protect the restriction site can be used to amplify the VH or VL sequences from a template, for example, scFv clones. Using cloning techniques known to those skilled in the art. Petition 870250103709, dated 12 / 11 / 2025, p. 111 / 179 In the art, PCR-amplified VH domains can be cloned into vectors expressing a VH constant region, and PCR-amplified VL domains can be cloned into vectors expressing a VL constant region, for example, human kappa or lambda constant regions. The sequences of the human kappa and lambda constant regions are known to those skilled in the art. Examples of human kappa and lambda constant region sequences are presented in SEQ ID Nos: 688-693. The VH and VL domains can also be cloned into a vector expressing the required constant regions. The heavy chain conversion vectors and light chain conversion vectors are then co-transfected into cell lines to generate stable or transient cell lines expressing full-length antibodies, for example, IgG, using techniques known to those skilled in the art.

[0217] A chimeric antibody is a molecule in which different portions of the antibody are derived from different immunoglobulin molecules. For example, a chimeric antibody may contain a variable region of a mouse or rat monoclonal antibody fused to a constant region of a human antibody. Methods for producing chimeric antibodies are known in the art. See, for example, Morrison SL (1985) Science 229: 1202 to 1207; Oi VT & Morrison SL (1986) BioTechniques 4: 214 to 221; Gillies SD et al., (1989) J Immunol Methods 125: 191-202; and US Patents Nos. 5,807,715, 4,816,567, 4,816,397 and 6,331,415, all of which are incorporated herein by reference in their entirety.

[0218] A humanized antibody is capable of binding to a predetermined antigen and comprises a structural region having substantially the amino acid sequence of a human immunoglobulin and CDRs having substantially the amino acid sequence of a non-human immunoglobulin (e.g., a murine immunoglobulin). In certain embodiments, a humanized antibody also comprises at least a portion of an immunoglobulin constant (Fc) region, typically that of a human immunoglobulin. The antibody may also include the CH1, hinge, CH2, CH3, and CH4 regions of the heavy chain. A humanized antibody may be selected from any class of Petition 870250103709, dated 12 / 11 / 2025, page 112 / 179 105 / 170 immunoglobulins, including IgM, IgG, IgD, IgA, and IgE, and any isotype, including IgG1, IgG2, IgG3, and IgG4. Humanized antibodies can be produced using a variety of techniques known in the art, including, but not limited to, CDR grafting (European Patent No. EP 239400; International Publication No. WO 91 / 09967; and US Patents Nos. 5,225,539, 5,530,101 and 5,585,089), coating or recoating (European Patents Nos. EP 592106 and EP 519596; Padlan EA (1991) Mol Immunol 28(4 / 5): 489 to 498; Studnicka GM et al., (1994) Engineering Prot 7(6): 805 to 814; (US Patent No. 5,565,332) and techniques disclosed, for example, in US Patent No. 6,407,213, Pat. US No. 5,766,886, International Publication No. WO 93 / 17105; Tan P et al., (2002) J Immunol 169: 1119 to 1125; Caldas C et al., (2000) Protein Eng. 13(5): 353 to 360; Morea V et al., (2000) Methods 20(3): 267 to 279; Baca M et al., (1997) J Biol Chem 272(16): 10678 to 10684; Roguska MA et al., (1996) Protein Eng 9(10): 895 904; Couto JR et al., (1995) Cancer Res. 55 (23 Supp): 5973s5977s; Couto JR et al., (1995) Cancer Res 55(8): 1717 to 1722; Sandhu JS (1994) Gene 150(2): 409 to 410; and Pedersen JT et al., (1994) J Mol Biol 235(3): 959 to 973, all of which are incorporated herein by reference in their entirety. See also U.S. Application Publication No. US 2005 / 0042664 A1 (February 24, 2005) and International Publication No. WO 2008 / 020079, which are incorporated herein by reference in their entirety.

[0219] Methods for producing multispecific antibodies (e.g., bispecific antibodies) have been described, see, for example, U.S. Patents Nos. 7,951,917; 7,183,076; 8,227,577; 5,837,242; 5,989,830; 5,869,620; 6,132,992; and 8,586,713, all of which are incorporated herein by reference in their entirety.

[0220] Bispecific and bivalent antibodies, and methods for producing them, are described, for example, in U.S. Patents Nos. 5,731,168, 5,807,706, 5,821,333 and U.S. Appl. Pat. Nos. 2003 / 020734 and 2002 / 0155537; each of which is incorporated herein by reference in its entirety. Tetravalent bispecific antibodies and methods for producing them are described, for example, in International Patent Application Publications Nos. WO 02 / 096948 and WO 00 / 44788, disclosures of which are Petition 870250103709, dated 12 / 11 / 2025, p. 113 / 179 106 / 170 incorporated herein by reference in their entirety. See, in general, International Publication Applications Nos. WO 93 / 17715, WO 92 / 08802, WO 91 / 00360 and WO 92 / 05793; Tutt et al., J. Immunol. 147:60-69 (1991); U.S. Pat. Nos. 4,474,893; 4,714,681; 4,925,648; 5,573,920; and 5,601,819; and Kostelny et al., J. Immunol. 148:1547 to 1553 (1992); each of which is incorporated herein by reference in its entirety.

[0221] A bispecific antibody as described in this document can be generated according to the DuoBody (Genmab A / S) technology platform as described, for example, in International Publications Nos. WO 2011 / 131746, WO 2011 / 147986, WO 2008 / 119353 and WO 2013 / 060867, and in Labrijn AF et al., (2013) PNAS 110(13): 5145 to 5150. The DuoBody technology can be used to combine half of a first monospecific antibody, or first antigen-binding region, containing two heavy and two light chains, with half of a second monospecific antibody, or second antigen-binding region, containing two heavy and two light chains. The resulting heterodimer contains a heavy chain and a light chain from the first antibody, or first antigen-binding region, paired with a heavy chain and a light chain from the second antibody, or second antigen-binding region.When both monospecific antibodies, or antigen-binding regions, recognize different epitopes on different antigens, the resulting heterodimer is a bispecific antibody.

[0222] DuoBody technology requires that each of the monospecific antibodies, or antigen-binding regions, include a constant heavy chain region with a single point mutation in the CH3 domain. Point mutations allow for a stronger interaction between the CH3 domains in the resulting bispecific antibody than between the CH3 domains in either of the monospecific antibodies or antigen-binding regions. The single point mutation in each monospecific antibody, or antigen-binding region, is at residue 366, 368, 370, 399, 405, 407, or 409, numbered according to the EU numbering system, in the CH3 domain of the constant heavy chain region, as described, for example, in International Publication No. WO 2011 / 131746. Furthermore, Petition 870250103709, dated 12 / 11 / 2025, pp. 114 / 179 107 / 170 A single point mutation is located at a different residue in one monospecific antibody, or antigen-binding region, compared to another monospecific antibody, or antigen-binding region. For example, one monospecific antibody, or antigen-binding region, may comprise the F405L mutation (i.e., a phenylalanine to leucine mutation at residue 405), while another monospecific antibody, or antigen-binding region, may comprise the K409R mutation (i.e., a lysine to arginine mutation at residue 409), numbered according to the EU numbering system. The constant regions of the heavy chain of monospecific antibodies, or antigen-binding regions, may be an IgG1, IgG2, IgG3, or IgG4 isotype (e.g., a human IgG1 isotype), and a bispecific antibody produced by DuoBody technology may retain Fc-mediated effector functions.

[0223] Another method for generating bispecific antibodies has been termed the “knobs-into-holes” strategy (see, for example, Pat. WO2006 / 028936). The mismatch of Ig heavy chains is reduced in this technology by mutating selected amino acids that form the interface of the CH3 domains in IgG. At positions within the CH3 domain where the two heavy chains directly interact, an amino acid with a small side chain (hole) is introduced into the sequence of one heavy chain and an amino acid with a large side chain (knob) into the counterpart location of the interacting residue in the other heavy chain. In some embodiments, the dissemination compositions have immunoglobulin chains in which the CH3 domains have been modified by mutating selected amino acids that interact at the interface between two polypeptides so as to preferentially form a bispecific antibody.Bispecific antibodies can be composed of immunoglobulin chains from the same subclass (e.g., IgG1 or IgG3) or from different subclasses (e.g., IgG1 and IgG3, or IgG3 and IgG4).

[0224] Bispecific antibodies may, in some cases, contain IgG4 and IgG1, IgG4 and IgG2, IgG4 and IgG3, or IgG1 and IgG3 chain heterodimers. Such heavy chain heterodimeric antibodies may routinely be Petition 870250103709, dated 12 / 11 / 2025, pp. 115 / 179 108 / 170 manipulated, for example, by modifying selected amino acids that form the interface of the CH3 domains in human IgG4 and IgGi or IgGe, in order to favor the formation of a heterodimeric heavy chain.

[0225] In certain embodiments, an antibody described herein that binds to the same PC epitope as an anti-PC antibody described herein is a human antibody. In certain embodiments, an antibody described herein that competitively blocks (e.g., in a dose-dependent manner) any of the antibodies described herein from binding to PC is a human antibody. Human antibodies can be produced using any method known in the art. For example, transgenic mice that are unable to express functional endogenous immunoglobulins but can express human immunoglobulin genes can be used. In particular, human heavy-chain and light-chain immunoglobulin gene complexes can be introduced randomly or by homologous recombination into mouse embryonic stem cells.Alternatively, the human variable region, the constant region, and the diversity region can be introduced into mouse embryonic stem cells, in addition to the human heavy and light chain genes. The mouse heavy and light chain immunoglobulin genes can be rendered non-functional separately or simultaneously with the introduction of human immunoglobulin loci by homologous recombination. In particular, homozygous deletion of the Jh region prevents endogenous antibody production. The modified embryonic stem cells are expanded and microinjected into blastocysts to produce chimeric mice. The chimeric mice are then reared to produce homozygous offspring expressing human antibodies. The transgenic mice are immunized normally with a selected antigen, e.g., all or part of an antigen (e.g., PC).Monoclonal antibodies directed against the antigen can be obtained from transgenic mice immunized using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation and... Petition 870250103709, dated 12 / 11 / 2025, pp. 116 / 179 109 / 170 subsequently undergo class switching and somatic mutation. Thus, using this technique, it is possible to produce therapeutically useful IgG, IgA, IgM, and IgE antibodies. For an overview of this technology for the production of human antibodies, see Lonberg N & Huszar D (1995) Int Rev Immunol 13:65-93, incorporated herein by reference in its entirety. For a detailed discussion of this technology for the production of human antibodies and human monoclonal antibodies and protocols for the production of such antibodies, see, for example, International Publications Nos. WO 98 / 24893, WO 96 / 34096, and WO 96 / 33735; and U.S. Patents Nos. 5,413,923, 5,625,126, 5,633,425, 5,569,825, 5,661,016, 5,545,806, 5,814,318 and 5,939,598, all of which are incorporated herein by reference in their entirety. Examples of mice capable of producing human antibodies include XenoMouse™ (Abgenix, Inc.; U.S. Patents Nos. 6,075,181 and 6,150,184), HuAb-Mouse™ (Medarex, Inc. / Gen Pharm; U.S. Patents Nos. 5,545).806 and 5,569,825), the TransChromo Mouse™ (Kirin) and the KM Mouse™ (Medarex / Kirin), all of which are incorporated herein by reference in their entirety.

[0226] Human antibodies that bind specifically to PC can be produced by a variety of methods known in the art, including the phage display methods described above using antibody libraries derived from human immunoglobulin sequences. See also U.S. Patents Nos. 4,444,887, 4,716,111 and 5,885,793; and International Publications Nos. WO 98 / 46645, WO 98 / 50433, WO 98 / 24893, WO 98 / 16654, WO 96 / 34096, WO 96 / 33735 and WO 91 / 10741, all of which are incorporated herein by reference in their entirety.

[0227] In certain embodiments, human antibodies can be produced using mouse-human hybridomas. For example, human peripheral blood lymphocytes transformed with the Epstein-Barr virus (EBV) can be fused with mouse myeloma cells to produce mouse-human hybridomas that secrete human monoclonal antibodies, and these mouse-human hybridomas can be screened to determine those that secrete human monoclonal antibodies that bind Petition 870250103709, dated 12 / 11 / 2025, pp. 117 / 179 110 / 170 specifically to a target antigen (e.g., PC). Such methods are known and described in the art, see, for example, Shinmoto H et al., (2004) Cytotechnology 46: 19 to 23; Naganawa Y et al., (2005) Human Antibodies 14: 27 to 31, each of which is incorporated herein by reference in its entirety. KITS

[0228] Kits comprising one or more antibodies described in this document, or pharmaceutical compositions or conjugates thereof, are also provided. In a specific embodiment, a pharmaceutical package or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions described in this document, such as one or more antibodies provided in this document, is provided in this document. In certain embodiments, the kits contain a pharmaceutical composition described in this document and any prophylactic or therapeutic agent, such as those described in this document. Optionally, associated with such containers may be a warning in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceutical or biological products, which warning reflects the agency's approval for manufacture, use or sale for human administration.

[0229] Kits that can be used in the above methods are also provided. In certain embodiments, a kit comprises an antibody described in this document, preferably a purified antibody, in one or more containers. In one specific embodiment, the kits described herein contain a substantially isolated PC antigen as a control. In another specific embodiment, the kits described herein further comprise a control antibody that does not react with PC antigen. In yet another specific embodiment, the kits described herein contain one or more elements for detecting the binding of an antibody to a PC antigen (for example, the antibody may be conjugated to a detectable substrate, such as a fluorescent compound, an enzymatic substrate, a radioactive compound, or a luminescent compound, or a second antibody that recognizes the first antibody may be conjugated to a detectable substrate).In specific embodiments, a kit provided here may include a recombinantly produced PC antigen or... Petition 870250103709, dated 12 / 11 / 2025, pp. 118 / 179 111 / 170 chemically synthesized. The PC antigen provided in the kit can also be attached to a solid support. In a more specific embodiment, the detection medium of the kit described above includes a solid support to which a PC antigen is attached. This kit may also include an anti-human or anti-mouse / rat antibody labeled with an unconjugated reporter. In this embodiment, the binding of the antibody to the PC antigen can be detected by the binding of the labeled antibody to the reporter. In certain embodiments, the present disclosure refers to the use of a kit of the present disclosure for in vitro analysis and / or detection of PC antigen in a biological sample. EXAMPLES

[0230] The following examples are offered for illustrative purposes only and are not exhaustive. EXAMPLE 1: SCREENING SUMMARY

[0231] A multifactorial optimization platform was used for antibody optimization. The platform was designed to optimize affinity, passive removal, thermostability, species cross-reactivity, and selective activation.

[0232] The heavy variable (VH) and kappa variable (VK) CDR sequences of E06 were grafted onto 4 fully human VH germlines (VH1-46, VH3-15, VH3-23, VH5-51) and 4 fully human VK germlines (VK1-39, VK2-28, VK3-15, VK4-1), respectively. Of the sixteen combinations made, two were selected for the construction of the platform library: E06_VK 1-39 / VH 3-23 and E06_VK 4-1 / VH 3-23. The individual VH and VK sequences are presented in Table 2. TABLE 2: VH AND VK SEQUENCES GRAFT. Sequence (underlined CDR sequences) SEQ ID NO: E06_VH3-23 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVR QAPGKGLEWVAASRNKANDYTTEYADSVKGRFTISRDNS KNTLYLQMNSLRAEDTAVYYCARDYYGSSYWYFDVWGQ GTLVTVSS 8 E06_VK1-39 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLA 685 Petition 870250103709, dated 12 / 11 / 2025, pp. 119 / 179 112 / 170 WYQQKPGKAPKLLIYGASNRYIGVPSRFSGSGSGTDFTLT ISSLQPEDFATYYCAQFYSYPLTFGQGTKVEIK E06_VK4-1 DIVMTQSPDSLAVSLGERATINCTASESLYSSKHKVHYLA WYQQKPGQPPKLLIYGASNRYIGVPDRFSGSGSGTDFTL TISSLQAEDVAVYYCAQFYSYPLTFGGGTKVEIK 269

[0233] The scFv structure-reformatted graft phage display libraries were designed based on structural and sequence analyses to retain CDR residues identified as exhibiting primary target-binding interactions. The remaining CDR residues were used for three-way sequence space-guided exploration to maximize the tolerability of human residues while limiting the potential impact on target binding. First, CDRH1, CDRH2, CDRL1, CDRL2, and CDRL3 were modified from parental CDRs to human germline CDRs with up to 4 alterations per CDR. Second, CDRH1, CDRH2, CDRL1, CDRL2, and CDRL3 were modified from the germline to parental CDR residues with up to four alterations. Third, all CDRs underwent single amino acid NNK walks, omitting residue alterations that would generate biochemical liabilities.The scFv E06 VK 1-39 / VH 3-23 and VK 4-1 / VH 3-23 libraries were combined, resulting in a total size of 4 x 109 transformers (referred to as the “platform library”).

[0234] Phosphocholine (PC)-conjugated peptides were used for phage selection and primary screening of scFv by ELISA. A summary of the PC-conjugated peptides used is presented in Table 3. TABLE 3: PHOSPHOCHOLINE (PC) CONJUGATED PEPTIDES USED FOR SCREENING. Peptide No. Conjugation Labeling Total Sequence 1 PC Biotin Biotin-AGGGGSGGGGSGGGGSAAA-[Tyr(PC)]acid (SEQ ID NO: 686) Petition 870250103709, dated 12 / 11 / 2025, pp. 120 / 179 113 / 170 2 PC - AGGGGSGGGGSGGGGSAAA-[Tyr (PC)]-acid (SEQ ID NO: 686) AEAAAKEAAAKAAAKAAAKAAA-[Tyr(PC)]-acid (SEQ ID NO: 687) 8 - Biotin Biotin-AEAAAKEAAAKAAAKAAAKAAA-Tyrácid (SEQ ID NO: 687) PC = p-diazophenyl phosphoryl choline

[0235] The phage-peptide complexes were captured in the biotin label of the peptides with streptavidin-coated beads. After washing, the bound phages were eluted with triethylamine and titrated to determine enrichment. After each panning round, the eluted phage was used to infect E. coli ER2738 for propagation of phage particles to be used in subsequent panning rounds.

[0236] Individual colonies of panning arms of Round 4 (380 colonies each; 1140 colonies total) were cultured and the scFvs were sequenced by Sanger. 736 unique sequences were pooled again in 96-well plates and subjected to primary screening by scFv ELISA on peptides 1, 4, 5, and 8.

[0237] A total of 368 ligands unique to peptide 5 and / or peptide 1 from the primary screening were regrouped and passed to secondary screening by ELISA (n=2) on peptides 1, 4, 5, and 8, as well as on BSA. A total of 257 unique scFvs were identified with good reproducibility between primary and secondary screening data and between replicates. These 257 sequences specifically bound to at least one of peptides 1 and 5, without binding to peptide 4, peptide 8, or BSA (the thresholds for positive OD450 were determined using the average OD450 for negative controls (one scFv specific for PD-1) +3x SD: Petition 870250103709, dated 12 / 11 / 2025, pp. 121 / 179 114 / 170 See Example 2 for the method). EXAMPLE 2: ELISA SUMMARY FOR scFv

[0238] Periplasmic extract (PPE) containing scFv was generated by osmotic shock. Starter cultures (2 x YT with 2% glucose, tetracycline (15 pg / mL) and carbenicillin (100 pg / mL), 700 pl / well in deep well plates) were inoculated with 5 to 10 pl of glycerol stock and cultured overnight at 30 °C and 700 rpm. The following day, expression cultures (2 x YT with 0.1% glucose and carbenicillin (100 pg / mL), 1 ml / well in deep well plates) were inoculated with 30 µl of starter culture and allowed to grow to OD600 0.5 at 37 °C and 700 rpm. Cultures were induced with 1 mM IPTG and cultured for 6 hours at 25 °C and 700 rpm.

[0239] After 6 hours, the plates were centrifuged to form bacterial pellets and stored overnight at -20°C. The following day, the pellets were thawed and resuspended in 80 µl of periplasmic extraction buffer with protease inhibitors and placed on a shaker for 10 minutes at 4°C and 500 rpm. After 10 minutes, 240 µl of water and protease inhibitor were added to each well and incubated for 1 hour at 4°C with shaking at 500 rpm. Then, the plates were centrifuged at 4300 xg for 10 minutes at 4°C. The supernatants were passed through a filter plate and stored at -80°C.

[0240] For ELISA analysis of scFv binding, 96-well polystyrene plates were coated with 1, 4, 5, 8, or 100 pL of BSA peptide (10 pg / mL) in PBS at 4°C overnight. The plates were washed three times with PBS-Tween and blocked with 100 pL of 1% BSA-TBS for 1 hour at room temperature. 96-well plates coated with streptavidin were coated with 100 pL of biotinylated PC peptides (1 pg / mL) in PBS for 1 hour at room temperature.

[0241] All plates were washed three times with PBSTween before 40 pL aliquots of PPE were added to the assay plates along with 50 pL of 10% BSA, and the plates were incubated for 1 hour at room temperature. After washing, 100 pL of anti-V5 were added. Petition 870250103709, dated 12 / 11 / 2025, pp. 122 / 179 115 / 170 conjugated with HRP in 5% BSA, and the plates were incubated at room temperature for 30 minutes. The plates were washed and 100 μL of TMB substrate was added. The color was allowed to develop at room temperature before the reaction was stopped with 100 μL of 1N HCl. The amount of scFv bound to each well was quantified from the absorbance measurement at 450 nm (OD450). The binding data for the 257 unique scFvs identified in Example 1 are summarized in Table 4. TABLE 4: ELISA DATA FOR scFv. Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB01_A06 1 181 0.74 0.06 1.18 0.06 0.10 PcOxP_DB01_A12 2 182 0.29 0.06 1.04 0.05 0.09 PcOxP_DB01_B01 3 183 0.87 0.07 0.90 0.05 0.10 PcOxP_DB01_B04 4 184 0.57 0.06 1.02 0.05 0.08 PcOxP_DB01_B05 5 185 0.23 0.05 0.74 0.05 0.10 PcOxP_DB01_B07 1 184 1.07 0.06 1.36 0.05 0.11 PcOxP_DB01_B08 6 ​​184 0.41 0.06 0.89 0.05 0.10 PcOxP_DB01_B09 1 186 1.00 0.05 1.42 0.05 0.10 PcOxP_DB01_B11 7 187 1.11 0.05 1.32 0.04 0.09 PcOxP_DB01_C01 8 188 0.71 0.06 1.13 0.05 0.11 PcOxP_DB01_C03 9 189 0.98 0.06 1.37 0.05 0.10 PcOxP_DB01_C04 10 190 1.38 0.05 1.42 0.05 0.08 PcOxP_DB01_C05 4 191 0.79 0.06 1.11 0.06 0.11 PcOxP_DB01_C06 11 192 1.18 0.05 1.31 0.05 0.08 PcOxP_DB01_C08 12 193 0.38 0.06 0.79 0.05 0.10 PcOxP_DB01_C12 13 194 0.88 0.05 1.18 0.05 0.08 PcOxP_DB01_D02 14 195 0.56 0.05 1.27 0.05 0.09 PcOxP_DB01_D05 15 196 0.87 0.06 1.56 0.05 0.10 PcOxP_DB01_D08 16 184 0.58 0.05 1.08 0.05 0.08 Petition 870250103709, dated 12 / 11 / 2025, pp. 123 / 179 116 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB01_D09 17 197 0.27 0.05 0.66 0.05 0.07 PcOxP_DB01_E04 18 198 0.55 0.05 1.12 0.04 0.07 PcOxP_DB01_E05 1 199 0.95 0.06 1.39 0.06 0.11 PcOxP_DB01_E06 19 200 0.68 0.05 1.05 0.05 0.09 PcOxP_DB01_E11 20 201 0.62 0.05 0.73 0.06 0.09 PcOxP_DB01_F04 21 202 0.36 0.05 0.57 0.05 0.09 PcOxP_DB01_F10 22 203 0.68 0.05 0.98 0.05 0.09 PcOxP_DB01_G01 23 204 0.58 0.06 1.33 0.05 0.09 PcOxP_DB01_G09 24 205 0.92 0.06 1.40 0.05 0.11 PcOxP_DB01_G11 25 184 0.99 0.06 1.32 0.06 0.09 PcOxP_DB01_G12 4 206 0.75 0.07 1.33 0.06 0.09 PcOxP_DB01_H04 26 207 2.01 0.07 1.92 0.07 0.11 PcOxP_DB01_H08 27 208 0.56 0.06 0.85 0.06 0.09 PcOxP_DB01_H10 28 209 0.60 0.06 1.39 0.06 0.08 PcOxP_DB02_A06 9 210 1.12 0.05 1.07 0.05 0.10 PcOxP_DB02_A09 29 211 0.98 0.05 1.30 0.04 0.11 PcOxP_DB02_A10 30 212 0.42 0.05 0.90 0.04 0.11 PcOxP_DB02_A11 31 213 0.64 0.04 0.89 0.04 0.09 PcOxP_DB02_A12 32 214 0.20 0.05 0.27 0.06 0.06 PcOxP_DB02_B02 33 215 0,49 0.05 0.98 0.05 0.11 PcOxP_DB02_B06 34 216 0.35 0.07 0.79 0.04 0.11 PcOxP_DB02_B10 17 217 0.67 0.04 1.03 0.04 0.08 PcOxP_DB02_B12 1 218 2.33 0.05 1.34 0.04 0.10 PcOxP_DB02_C01 35 184 1.03 0.06 1.47 0.05 0.10 PcOxP_DB02_C02 36 184 0.35 0.05 0.62 0.05 0.10 PcOxP_DB02_C06 35 219 0.54 0.05 1.03 0.05 0.11 PcOxP_DB02_C09 35 220 0.69 0.05 1.01 0.04 0.10 PcOxP_DB02_C11 37 184 0.12 0.05 0.24 0.04 0.10, Petition 870250103709, dated 12 / 11 / 2025, pp. 124 / 179 117 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB02_D01 38 221 0.31 0.05 0.35 0.05 0.09 PcOxP_DB02_D09 39 222 0.16 0.05 0.44 0.04 0.11 PcOxP_DB02_D10 9 223 0.69 0.05 1.01 0.04 0.10 PcOxP_DB02_E01 9 224 0.43 0.05 0.63 0.10 0.11 PcOxP_DB02_E06 40 184 0.06 0.04 0.08 0.04 0.10 PcOxP_DB02_E10 41 225 0.52 0.04 0.79 0.04 0.09 PcOxP_DB02_F02 8 226 0.37 0.05 0.60 0.05 0.11 PcOxP_DB02_F07 42 227 0.43 0.05 0.91 0.05 0.10 PcOxP_DB02_F12 35 228 0.50 0.04 0.81 0.04 0.07 PcOxP_DB02_G06 43 229 0.43 0.06 0.87 0.05 0.08 PcOxP_DB02_G07 4 230 0.52 0.05 0.99 0.09 0.10 PcOxP_DB02_G09 9 231 0.35 0.05 0.71 0.04 0.10 PcOxP_DB02_H03 8 232 0.27 0.05 0.82 0.05 0.08 PcOxP_DB02_H10 1 233 1.43 0.05 1.39 0.05 0.08 PcOxP_DB03_A03 8 234 0.54 0.06 0.81 0.06 0.09 PcOxP_DB03_A08 44 184 0.67 0.06 0.71 0.05 0.11 PcOxP_DB03_A09 1 235 1.02 0.05 1.09 0.05 0.09 PcOxP_DB03_A11 45 236 1.12 0.05 1.08 0.05 0.08 PcOxP_DB03_B02 30 237 2.02 0.05 1.64 0.05 0.07 PcOxP_DB03_C03 46 184 1.36 0.05 1,66 0.05 0.09 PcOxP_DB03_C06 47 238 0.64 0.05 0.61 0.05 0.07 PcOxP_DB03_C11 48 239 1.14 0.05 0.75 0.04 0.07 PcOxP_DB03_C12 1 230 2.74 0.05 1.77 0.05 0.09 PcOxP_DB03_D01 49 190 2.51 0.05 1.60 0.05 0.08 PcOxP_DB03_D07 44 240 0.75 0.06 0.95 0.05 0.12 PcOxP_DB03_D08 50 184 0.54 0.05 0.57 0.05 0.10 PcOxP_DB03_D11 51 241 0.50 0.06 0.66 0.05 0.08 PcOxP_DB03_E01 52 242 2.50 0.06 2.11 0.06 0.09, Petition 870250103709, dated 12 / 11 / 2025, pp. 125 / 179 118 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB03_E02 53 243 2.00 0.06 1.49 0.05 0.11 PcOxP_DB03_E07 54 184 0.78 0.05 0.86 0.05 0.08 PcOxP_DB03_E08 55 244 0.87 0.05 0.92 0.05 0.09 PcOxP_DB03_E09 56 245 0.39 0.05 0.72 0.05 0.08 PcOxP_DB03_F01 57 246 0.58 0.05 0.80 0.05 0.09 PcOxP_DB03_F10 58 247 0.65 0.05 0.85 0.07 0.09 PcOxP_DB03_G02 59 248 1.33 0.04 1.59 0.05 0.07 PcOxP_DB03_G03 60 249 1.57 0.05 1.80 0.08 0.08 PcOxP_DB03_G06 8 250 2.48 0.06 2.01 0.06 0.10 PcOxP_DB03_G07 61 184 2.18 0.06 1.67 0.05 0.10 PcOxP_DB03_G10 35 251 1.80 0.05 1.21 0.05 0.11 PcOxP_DB03_H03 62 252 0.27 0.07 1.32 0.07 0.12 PcOxP_DB03_H07 1 253 1.91 0.05 1.64 0.05 0.08 PcOxP_DB03_H08 63 254 0.91 0.06 1.18 0.06 0.12 PcOxP_DB03_H09 64 181 0.93 0.06 1.25 0.06 0.11 PcOxP_DB04_A07 65 255 1.54 0.05 2.11 0.05 0.09 PcOxP_DB04_A09 66 256 1.16 0.06 1.96 0.06 0.12 PcOxP_DB04_A10 67 257 0.74 0.06 1.61 0.06 0.11 PcOxP_DB04_A12 68 198 0.71 0.07 1.38 0.06 0.12 PcOxP_DB04_B06 35 258 0,66 0.06 1.06 0.06 0.10 PcOxP_DB04_B08 69 259 1.33 0.06 1.56 0.05 0.11 PcOxP_DB04_C03 70 260 1.34 0.06 1.87 0.06 0.10 PcOxP_DB04_C08 71 261 0.69 0.05 1.07 0.06 0.08 PcOxP_DB04_D08 72 262 1.60 0.07 1.96 0.07 0.12 PcOxP_DB04_F06 73 263 0.75 0.06 1.30 0.06 0.10 PcOxP_DB04_F11 74 264 0.58 0.07 1.27 0.06 0.10 PcOxP_DB04_G06 75 265 1.03 0.07 1.12 0.07 0.11 PcOxP_DB04_H03 76 266 0.80 0.07 1.05 0.08 0.10, Petition 870250103709, dated 12 / 11 / 2025, pp. 126 / 179 119 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB04_H07 77 267 0.58 0.06 1.02 0.05 0.09 PcOxP_DB04_H08 4 205 0.85 0.07 1.42 0.06 0.09 PcOxP_DB04_H10 78 268 0.54 0.08 1.01 0.07 0.10 PcOxP_DB01_A03 1 269 0.86 0.05 1.38 0.04 0.07 PcOxP_DB01_A04 27 269 0.31 0.04 0.75 0.04 0.07 PcOxP_DB01_A05 79 269 0.83 0.04 1.28 0.04 0.06 PcOxP_DB01_A08 80 270 0.16 0.05 1.12 0.05 0.09 PcOxP_DB01_B02 81 269 0.68 0.06 1.41 0.05 0.09 PcOxP_DB01_B03 22 269 0.82 0.05 1.25 0.05 0.08 PcOxP_DB01_B06 82 269 0.79 0.05 1.45 0.05 0.08 PcOxP_DB01_B10 83 271 0.52 0.05 1.11 0.04 0.08 PcOxP_DB01_B12 84 272 0.56 0.06 1.19 0.05 0.09 PcOxP_DB01_C07 1 273 0.53 0.04 1.10 0.04 0.05 PcOxP_DB01_C09 8 274 0.27 0.05 0.94 0.05 0.07 PcOxP_DB01_C10 8 275 0.13 0.04 0.53 0.04 0.07 PcOxP_DB01_D01 22 276 0.85 0.05 1.12 0.04 0.06 PcOxP_DB01_D04 8 277 0.45 0.08 0.87 0.06 0.07 PcOxP_DB01_D06 85 278 0.41 0.04 0.69 0.04 0.06 PcOxP_DB01_D07 86 279 0.14 0.04 0.60 0.04 0.05 PcOxP_DB01_D10 87 269 0.15 0,05 0.44 0.04 0.06 PcOxP_DB01_D11 88 280 1.37 0.06 2.09 0.05 0.08 PcOxP_DB01_D12 89 269 0.85 0.05 1.48 0.05 0.06 PcOxP_DB01_E01 60 281 0.75 0.05 1.48 0.04 0.05 PcOxP_DB01_E02 90 269 0.46 0.05 1.02 0.05 0.07 PcOxP_DB01_E03 91 282 0.86 0.05 1.54 0.05 0.08 PcOxP_DB01_E07 22 283 0.87 0.05 1.51 0.05 0.07 PcOxP_DB01_E08 92 269 0.47 0.05 0.82 0.04 0.06 PcOxP_DB01_E09 93 284 0.77 0.04 1.26 0.04 0.06, Petition 870250103709, dated 12 / 11 / 2025, pp. 127 / 179 120 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB01_E10 94 285 0.60 0.07 1.11 0.07 0.11 PcOxP_DB01_F01 95 286 0.60 0.05 1.78 0.05 0.08 PcOxP_DB01_F03 96 269 0.80 0.07 1.41 0.08 0.08 PcOxP_DB01_F06 73 287 0.12 0.04 0.53 0.04 0.07 PcOxP_DB01_F07 97 288 0.31 0.04 0.81 0.04 0.06 PcOxP_DB01_F08 68 289 0.52 0.04 1.22 0.04 0.06 PcOxP_DB01_F11 98 269 1.55 0.07 1.92 0.05 0.07 PcOxP_DB01_F12 99 290 0.76 0.05 1.43 0.05 0.06 PcOxP_DB01_G02 100 291 0.82 0.05 1.20 0.04 0.06 PcOxP_DB01_G03 4 292 0.43 0.05 0.94 0.05 0.07 PcOxP_DB01_G04 4 289 0.56 0.05 1.01 0.07 0.07 PcOxP_DB01_G05 101 284 0.69 0.05 1.24 0.05 0.08 PcOxP_DB01_G06 66 289 0.73 0.05 1.32 0.04 0.06 PcOxP_DB01_G07 89 293 0.46 0.05 1.20 0.04 0.07 PcOxP_DB01_G10 102 294 0.71 0.05 1.52 0.05 0.10 PcOxP_DB01_H01 103 269 ​​0.82 0.07 1.23 0.06 0.09 PcOxP_DB01_H02 22 295 0.74 0.07 1.10 0.06 0.10 PcOxP_DB01_H03 104 296 0.46 0.07 1.29 0.06 0.10 PcOxP_DB01_H06 105 297 0.96 0.05 1.79 0.07 0,11 PcOxP_DB01_H07 106 270 0.10 0.05 0.92 0.05 0.07 PcOxP_DB01_H09 107 269 0.06 0.09 0.09 0.04 0.09 PcOxP_DB02_A04 67 269 0.33 0.04 0.82 0.04 0.09 PcOxP_DB02_A05 62 298 0.99 0.05 1.24 0.04 0.07 PcOxP_DB02_B04 66 269 0.75 0.05 1.32 0.04 0.08 PcOxP_DB02_B07 108 299 0.40 0.04 0.77 0.04 0.06 PcOxP_DB02_B09 109 300 0.27 0.04 0.83 0.04 0.07 PcOxP_DB02_C03 110 301 0.54 0.05 0.61 0.05 0.10 PcOxP_DB02_C04 111 302 0.37 0.05 0.75 0.05 0.08, Petition 870250103709, dated 12 / 11 / 2025, pp. 128 / 179 121 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB02_C05 112 269 0.64 0.04 0.92 0.04 0.06 PcOxP_DB02_C08 113 303 0.22 0.06 0.39 0.04 0.06 PcOxP_DB02_C10 1 304 0.44 0.04 0.92 0.04 0.06 PcOxP_DB02_C12 72 305 0.97 0.04 1.58 0.04 0.07 PcOxP_DB02_D02 114 306 0.16 0.04 0.27 0.04 0.05 PcOxP_DB02_D03 115 307 0.42 0.04 0.71 0.04 0.08 PcOxP_DB02_E02 116 269 0.09 0.04 0.34 0.05 0.06 PcOxP_DB02_E03 117 308 0.39 0.04 0.75 0.05 0.08 PcOxP_DB02_E08 118 269 0.24 0.04 0.49 0.04 0.07 PcOxP_DB02_E09 110 309 0.56 0.04 0.74 0.04 0.07 PcOxP_DB02_E11 119 310 0.23 0.04 0.76 0.04 0.06 PcOxP_DB02_E12 120 311 0.26 0.05 0.58 0.06 0.06 PcOxP_DB02_F04 121 269 0.47 0.04 0.74 0.05 0.09 PcOxP_DB02_F06 122 312 0.16 0.04 0.45 0.04 0.06 PcOxP_DB02_F09 123 289 0.39 0.04 0.93 0.04 0.08 PcOxP_DB02_F10 9 313 0.51 0.05 1.20 0.04 0.09 PcOxP_DB02_F11 124 314 0.23 0.04 0.66 0.04 0.08 PcOxP_DB02_G02 120 289 1.01 0.04 1.13 0.04 0.06 PcOxP_DB02_G03 125 315 0.06 0.05 0.10 0.05 0,06 PcOxP_DB02_G04 110 316 0.32 0.05 0.70 0.05 0.11 PcOxP_DB02_G05 126 317 1.49 0.05 1.80 0.07 0.11 PcOxP_DB02_H02 127 318 0.07 0.04 0.19 0.06 0.06 PcOxP_DB02_H04 49 319 0.22 0.05 0.20 0.04 0.06 PcOxP_DB02_H05 128 320 0.20 0.04 0.44 0.04 0.09 PcOxP_DB02_H06 9 321 0.92 0.05 1.04 0.05 0.07 PcOxP_DB02_H07 22 322 0.56 0.04 0.88 0.05 0.07 PcOxP_DB02_H08 129 323 0.40 0.04 1.34 0.06 0.07 PcOxP_DB02_H09 130 269 0.25 0.04 0.58 0.04 0.07, Petition 870250103709, dated 12 / 11 / 2025, pp. 129 / 179 122 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB03_A04 131 324 0.19 0.04 0.47 0.04 0.06 PcOxP_DB03_A05 132 325 0.93 0.04 0.78 0.04 0.06 PcOxP_DB03_A06 133 326 0.99 0.05 1.07 0.05 0.08 PcOxP_DB03_A07 134 327 0.94 0.04 1.01 0.04 0.06 PcOxP_DB03_A10 53 328 0.60 0.04 0.54 0.04 0.06 PcOxP_DB03_A12 135 272 2.28 0.06 1.67 0.05 0.07 PcOxP_DB03_B01 136 329 0.21 0.04 0.64 0.04 0.06 PcOxP_DB03_B03 4 301 1.12 0.04 1.10 0.04 0.07 PcOxP_DB03_B06 137 330 0.68 0.04 1.01 0.05 0.06 PcOxP_DB03_B07 138 269 0.66 0.06 0.81 0.05 0.12 PcOxP_DB03_B08 1 284 2.63 0.05 1.95 0.04 0.07 PcOxP_DB03_B09 22 331 1.09 0.05 0.89 0.05 0.08 PcOxP_DB03_B10 139 269 ​​0.41 0.05 0.71 0.05 0.08 PcOxP_DB03_B11 140 332 0.50 0.05 0.72 0.05 0.07 PcOxP_DB03_B12 141 269 1.21 0.05 0.85 0.05 0.06 PcOxP_DB03_C01 142 333 0.84 0.05 1.47 0.05 0.08 PcOxP_DB03_C04 143 334 2.11 0.04 1.72 0.04 0.07 PcOxP_DB03_C08 144 335 0.98 0.05 0.90 0.05 0.06 PcOxP_DB03_C10 101 298 1.10 0.05 1.10 0.04 0,07 PcOxP_DB03_D02 1 336 0.67 0.05 1.37 0.04 0.09 PcOxP_DB03_D03 145 269 0.73 0.04 1.11 0.04 0.10 PcOxP_DB03_D10 146 337 1.19 0.05 1.41 0.06 0.06 PcOxP_DB03_D12 147 269 0.20 0.04 0.30 0.04 0.06 PcOxP_DB03_E03 17 338 0.27 0.04 0.79 0.04 0.05 PcOxP_DB03_E04 22 320 0.96 0.06 1.20 0.04 0.08 PcOxP_DB03_E11 4 339 1.40 0.05 1.58 0.04 0.07 PcOxP_DB03_E12 148 340 0.57 0.06 0.88 0.06 0.06 PcOxP_DB03_F02 149 341 1.56 0.05 1.68 0.05 0.07, Petition 870250103709, dated 12 / 11 / 2025, pp. 130 / 179 123 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB03_F03 150 342 1.13 0.05 1.93 0.05 0.08 PcOxP_DB03_F05 151 343 0.73 0.05 1.04 0.04 0.06 PcOxP_DB03_F07 152 344 0.53 0.05 1.19 0.05 0.08 PcOxP_DB03_F09 94 289 0.72 0.05 1.12 0.05 0.08 PcOxP_DB03_F11 153 345 1.47 0.06 1.43 0.06 0.12 PcOxP_DB03_G01 154 346 0.66 0.05 1.19 0.05 0.09 PcOxP_DB03_G09 155 347 0.74 0.05 1.07 0.05 0.07 PcOxP_DB03_G11 22 348 0.26 0.05 0.72 0.05 0.10 PcOxP_DB03_G12 89 282 1.57 0.06 1.91 0.05 0.08 PcOxP_DB03_H02 156 349 1.07 0.05 1.69 0.04 0.05 PcOxP_DB03_H10 157 296 0.24 0.04 0.39 0.07 0.05 PcOxP_DB04_A04 158 350 1.09 0.08 1.90 0.08 0.11 PcOxP_DB04_A05 159 329 0.72 0.04 1.29 0.04 0.06 PcOxP_DB04_A11 24 351 0.64 0.07 1.60 0.08 0.10 PcOxP_DB04_B01 160 352 0.45 0.05 0.78 0.05 0.06 PcOxP_DB04_B07 161 269 0.93 0.06 1.33 0.05 0.09 PcOxP_DB04_B10 162 353 1.05 0.05 1.56 0.04 0.06 PcOxP_DB04_B11 163 269 0.26 0.05 0.31 0.05 0.08 PcOxP_DB04_B12 1 354 0.13 0.04 0.34 0.04 0,09 PcOxP_DB04_C09 164 355 0.55 0.07 1.21 0.06 0.11 PcOxP_DB04_C10 165 269 0.54 0.06 1.03 0.05 0.08 PcOxP_DB04_C11 1 356 0.81 0.05 1.34 0.04 0.07 PcOxP_DB04_D01 166 357 1.23 0.06 1.66 0.06 0.07 PcOxP_DB04_D05 167 358 0.87 0.05 1.27 0.06 0.08 PcOxP_DB04_D07 110 334 1.02 0.05 1.05 0.05 0.08 PcOxP_DB04_D09 87 359 0.41 0.05 0.83 0.08 0.06 PcOxP_DB04_D10 168 360 1.14 0.05 1.35 0.05 0.07 PcOxP_DB04_D12 169 269 0.64 0.06 1.03 0.05 0.08, Petition 870250103709, dated 12 / 11 / 2025, pp. 131 / 179 124 / 170 Binder SEQ ID NO: OD450 VH VL Peptide 1 Peptide 4 Peptide 5 Peptide 8 BSA PcOxP_DB04_E05 170 269 0.67 0.06 1.03 0.05 0.09 PcOxP_DB04_E06 171 269 1.04 0.04 1.59 0.05 0.07 PcOxP_DB04_E08 172 361 1.39 0.06 2.01 0.05 0.09 PcOxP_DB04_E12 8 362 1.03 0.05 1.39 0.05 0.07 PcOxP_DB04_F01 173 304 0.56 0.07 0.85 0.07 0.09 PcOxP_DB04_F03 174 269 0.58 0.06 0.87 0.05 0.10 PcOxP_DB04_F05 1 363 0.76 0.06 0.97 0.05 0.07 PcOxP_DB04_G01 175 364 0.63 0.07 1.39 0.09 0.09 PcOxP_DB04_G03 176 365 0.19 0.04 0.40 0.05 0.07 PcOxP_DB04_G05 177 269 1.20 0.05 1.67 0.05 0.07 PcOxP_DB04_G08 178 366 1.39 0.05 1.67 0.05 0.07 PcOxP_DB04_G09 179 269 0.48 0.05 1.08 0.06 0.08 PcOxP_DB04_G11 180 367 0.68 0.05 0.79 0.05 0.07 PcOxP_DB04_H01 89 368 1.22 0.06 1.80 0.07 0.07 EXAMPLE 3: SUMMARY OF ELISA FOR IgG

[0242] 48 scFv were selected and reformatted along with the parental antibody E06 in human IgG1 using standard techniques. For ELISA antibody binding analysis, 384-well polystyrene microtiter plates were coated with 20 pL of antigen (PC-BSA at 5 pg / mL) in PBS for 2 hours at room temperature. The plates were washed three times with DELFIA® washing buffer and then blocked with 20 pL / well of 1% BSA-TBS for 1 hour at room temperature. After washing, 15 pL of the antibody titrated in 1% BSA-TBS were added to the wells and incubated for 1 hour at room temperature. After another wash, 15 pL / well of DELFIA® Eu-N1 Anti-Human IgG secondary antibody in TBS were added to the wells and incubated for 1 hour at room temperature. The plates were washed again, and the amount of connection Petition 870250103709, dated 12 / 11 / 2025, pp. 132 / 179 The antibody concentration (125 / 170) in each well was quantified from TRF measurement after 5 minutes of incubation at room temperature with DELFIA® enhancement buffer. Binding data for the parental IgG1 antibody E06 and various IgG1 ligands are summarized in Table 5. No BSA binding was detected for any of the antibodies shown in Table 5.

[0243] The physical properties (melting point, aggregation temperature, and polydispersity index) of the antibodies were determined using an Uncle instrument (Unchained Labs). The physical properties of the parental IgG1 antibody E06 and of various IgG1 ligands are summarized in Table 5. TABLE 5: ELISA DATA FOR IgG. EC50 Antibody (nM) Physical Properties PC BSA Melting Point Tm (°C) Aggregation Points Tagg (°C) Polydispersity Index (PDI) E06 Parental IgG1 0.390 69.5 66.3 0.07 PcOxP_DB01_G05 0.263 71.5 71.65 0.246 PcOxP_DB01_G09 0.308 72.5 73.44 0.058 PcOxP_DB01_H01 0.275 71.58 74.57 0.093 PcOxP_DB03_B11 0.299 71.24 74.52 0.104 PcOxP_DB03_C10 0.285 72 73.29 0.167 PcOxP_DB03_H08 0.445 68.7 69.56 0.182 PcOxP_DB04_A11 0.413 71.5 72.03 0.097 PcOxP_DB04_E05 0.282 70.53 72.22 0.126 PcOxP_DB01_A06 0.43 71.21 72.53 0.197 PcOxP_DB01_B09 0.317 71.5 74.55 0.036 PcOxP_DB01_C04 0.310 33.5 72.81 0.11 PcOxP_DB01_D01 0.274 70.5 70.73 0.029 PcOxP_DB01_D11 0.242 69.14 69.67 0.124 PcOxP_DB01_E05 0.417 71.5 73.26 0.106 Petition 870250103709, dated 12 / 11 / 2025, pp. 133 / 179 126 / 170 EC50 Antibody (nM) Physical Properties PC BSA Melting Point Tm (°C) Aggregation point Tagg (°C) Polydispersity index (PDI) PcOxP_DB01_E10 0.316 72.2 74.66 0.172 PcOxP_DB01_F01 0.672 73 72.68 0.347 PcOxP_DB01_G10 0.407 71.5 72.96 0.027 PcOxP_DB01_H02 0.43 72.12 74.88 0.304 PcOxP_DB01_H04 0.456 72 72.97 0.436 PcOxP_DB02_A06 0.643 70 70.54 0.235 PcOxP_DB02_C01 0.64 71.5 72.51 0.207 PcOxP_DB02_H07 0.423 71.74 74.2 0.192 PcOxP_DB03_A09 0.664 70.5 72.92 0.095 PcOxP_DB03_B09 0.426 71 73.2 0.047 PcOxP_DB03_C03 0.339 70.22 73.18 0.231 PcOxP_DB03_C12 0.436 70 73.79 0.098 PcOxP_DB03_D08 0.401 70.23 71.27 0.149 PcOxP_DB03_E01 0.857 72.01 73.07 0.166 PcOxP_DB03_G07 0.636 73.06 74.2 0.223 PcOxP_DB03_G12 0.557 72.74 73.67 0.06 PcOxP_DB04_A09 0.269 72.5 72.15 0.023 PcOxP_DB04_E08 0.251 72.73 76.24 0.167 PcOxP_DB01_F06 0.216 72.18 71.28 0.219 PcOxP_DB02_F10 0.659 72 73.59 0.12 PcOxP_DB02_G04 0.231 70 67.12 0.143 PcOxP_DB04_G01 0.257 72.5 74.34 0.288 PcOxP_DB01_B06 0.219 72.6 74.28 0,437 PcOxP_DB01_F04 0.344 71 70.95 0.184 PcOxP_DB01_F11 0.244 71.18 76.16 0.074 PcOxP_DB01_H08 0.244 70.51 70.08 0.092 PcOxP_DB02_A05 0.264 71.5 73.63 0.25, Petition 870250103709, dated 12 / 11 / 2025, pp. 134 / 179 127 / 170 EC50 Antibody (nM) Physical Properties PC BSA Melting Point Tm (°C) Aggregation Point Tagg (°C) Polydispersity Index (PDI) PcOxP_DB02_B04 0.278 71.58 76.93 0.078 PcOxP_DB03_F09 0.28 72.62 73.62 0.129 PcOxP_DB03_G03 0.216 58.52 73.65 0.22 PcOxP_DB03_G11 0.244 73.06 74.11 0.217 PcOxP_DB03_H03 0.229 70.5 70.1 0.156 PcOxP_DB04_A04 0.294 74 76.96 0.134 PcOxP_DB02_C09 0.394 72 68.48 0.265 EXAMPLE 4: ADDITIONAL CHARACTERIZATION OF IgG

[0244] Selected human IgG1 antibodies (see Example 3) were subsequently analyzed for antibody yield, stress test, and immunogenicity characteristics. Yield was determined by transfecting HEK293 cells and subsequent expression in 25 mL cultures. For several antibodies, yield was determined in a larger-scale 40 L transient transfection culture. Antibody products were purified using protein A, and the resulting amount of antibody was measured by absorbance at 280 nm (OD280). Yield values ​​for the parent antibody E06 IgG1 and selected IgG1 ligands are shown in Table 6. TABLE 6: INCOME DATA. Antibody Yield - 25 mL culture (mg) Yield - 40 L culture (mg / L) E06 parental IgG1 -- 15 PcOxP_DB01_H08 3.3 649 PcOxP_DB03_C03 3.4 392 PcOxP_DB01_F11 8.5 PcOxP_DB01_B09 5.2 PcOxP_DB01_G09 4.8 Petition 870250103709, dated 12 / 11 / 2025, pp. 135 / 179 128 / 170 PcOxP_DB03_C12 3.1 PcOxP_DB01_E05 5.1

[0245] Parental IgG1 antibody E06 and human IgG1 antibody PcOxP_DB01_H08 were analyzed in forced degradation studies to compare the relative stability and stress resistance between the antibodies. Samples of each antibody were subjected to temperature stress, oxidation stress, and low and high pH stress, and the samples were analyzed and compared to unstressed samples. Several analytical techniques were used to analyze the samples. In addition to concentration measurement and visual inspection, chemical stability was assessed by RPC-MS at the protein level at the intact and reduced antibody level, peptide mapping analysis under reducing conditions, iCIEF analysis and CGE-SDS under non-reducing and reducing conditions, and physical stability was assessed by SE-HPLC.

[0246] For temperature stress, samples of each antibody were stored at 40 °C for 2 weeks, 3 weeks, or 4 weeks. For low pH stress, the pH in the samples of each antibody was adjusted to 3.2 using 0.12M HCl, and the samples were incubated at 25 °C for 2 hours before changing the buffer back to the formulation buffer. For high pH stress (forced deamidation), the pH in the samples of each antibody was adjusted to 9.0 using 0.5 M Tris pH 11, and the samples were incubated for 3 days at 37 °C before changing the buffer back to the formulation buffer. For oxidative stress, a 3% H2O2 solution was added to the samples of each antibody to achieve a final concentration of 0.03%, and the samples were incubated for 1 day at 25 °C before changing the buffer back to the formulation buffer.The results of the stress test and stability assay are summarized qualitatively in Table 7 (“+”: moderately stable; “++”: highly stable). TABLE 7: STRESS TEST AND STABILITY COMPARISON. Petition 870250103709, dated 12 / 11 / 2025, pp. 136 / 179 129 / 170 Antibody Storage at 40°C Low pH stress Forced deamidation Oxidative stress Parental E06 IgG1 + ++ + ++ PcOxP_DB01_H08 ++ ++ ++ ++

[0247] The in vivo immunogenicity of the parental IgG1 antibody E06 and the human IgG1 antibodies PcOxP_DB01_H08 and PcOxP_DB03_C03 was predicted using the Epibase® in vitro immunogenicity assay (Lonza Biologics), the Epibase® in silico platform (Lonza Biologics), and the ISPRI™ in silico platform (EpiVax, Inc.). Immunogenicity profiles are summarized in Table 8. Overall, the immunogenicity assays show that PcOxP_DB01_H08 and PcOxP_DB03_C03 have a low risk of immunogenicity and a favorable profile when compared to several established antibody drugs. TABLE 8: IMMUNOGENICITY ASSAY DATA. Epibase® antibody in vitro (% of responders)* Epibase® score in silico ISPRI™ score in silico** Parental IgG1 E06 17 2203 7.44 PcOxP_DB01_H08 16 906 -50.09 PcOxP_DB03_C03 22 1048 — *: 32 donor samples, the positive KLH control shows 100% effect **: a score of 0 indicates predicted immunogenic responses in approximately 5% of patients SEQUENCE LISTING SEQ ID NO SEQUENCE 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 2 EVQLLESGGGLVQPGGSLRLSCAASGFGFSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC Petition 870250103709, dated 12 / 11 / 2025, pp. 137 / 179 130 / 170 ARDYYGSSYWYYDVWGQGTLVTVSS 3 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYIEWVRQAPGKGLEWVA ASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYLGSSYWYFDVWGQGTLVTVSS 4 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 5 EVQLLESGGGLVQPGGSLRLSCAASGFTASDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 6 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDSYMEWVRQAPGKGLEWV AASRNKANDYTTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 7 EVQLLESGGGLVQPGGSLRLSCAASGFTFEDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYFGSSYWYFDVWGQGTLVTVSS 8 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 9 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 10 EVQLLESGGGLVQPGGSLRLSCAASGFQFSDFYMEWVRQAPGKGLEWVAASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 11 EVQLLESGGGLVQPGGSLRLSCAASGFEFSDNYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 12 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYASSYWYFDVWGQGTLVTVSS 13 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTELADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 14 EVQLLESGGGLVQPGGSLRLSCAASGFEFSDFYMEWVRQAPGKGLEWV AASRGKGNSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 15 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV Petition 870250103709, dated 12 / 11 / 2025, pp. 138 / 179 131 / 170 AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSPYWYFDVWGQGTLVTVSS 16 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDAYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDSWGQGTLVTVSS 17 EVQLLESGGGLVQPGGSLRLSCAASGFTESDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 18 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDAYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDTWGQGTLVTVSS 19 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDLWGQGTLVTVSS 20 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYVTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 21 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 22 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 23EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRNKGNSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 24 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANTYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 25 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKNNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYFGSSYWYFDVWGQGTLVTVSS 26 EVQLLESGGGLVQPGGSLRLSCAASGFAFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSHYWYFDVWGQGTLVTVSS 27 EVQLLESGGGLVQPGGSLRLSCAASGFTHSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS Petição 870250103709, de 12 / 11 / 2025, pág. 139 / 179 132 / 170 28 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKNNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 29 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDTYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 30 EVQLLESGGGLVQPGGSLRLSCAASGFAFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 31 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNIANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 32 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDDYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYQGSSYWYFDVWGQGTLVTVSS 33 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNSGNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 34 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDNYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 35 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDAYMEWVRQAPGKGLEWVAASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 36 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTVEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGHSYWYFDVWGQGTLVTVSS 37 EVQLLESGGGLVQPGGSLRLSCAASGFTSSDFYMEWVRQAPGKGLEWV AASRNKANDYYTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 38 EVQLLESGGGLVQPGGSLRLSCAASGFGFSDFYMEWVRQAPGKGLEWV AASRHKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 39 EVQLLESGGGLVQPGGSLRLSCAASGFTFSTFYMEWVRQAPGKGLEWVA ASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 40 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDEYMEWVRQAPGKGLEWV AASRGKGNSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC Petição 870250103709, de 12 / 11 / 2025, pág. 140 / 179 133 / 170 ARDYYGSSYWYFDVWGQGTLVTVSS 41 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNKANDYQTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 42 EVQLLESGGGLVQPGGSLRLSCAASGFWFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 43 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNQANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSPYWYFDVWGQGTLVTVSS 44 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDVYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 45 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNQANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYLDVWGQGTLVTVSS 46 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 47 EVQLLESGGGLVQPGGSLRLSCAASGATFSDFYMEWVRQAPGKGLEWV AASRNGANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGNSYWYFDVWGQGTLVTVSS 48 EVQLLESGGGLVQPGGSLRLSCAASGFDFSDFYMEWVRQAPGKGLEWVAASRNKANDYTTDYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYFGSSYWYFDVWGQGTLVTVSS 49 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDEYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 50 EVQLLESGGGLVQPGGSLRLSCAASGFWFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSAYWYFDVWGQGTLVTVSS 51 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGHSYWYFDVWGQGTLVTVSS 52 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANDYTVEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 53 EVQLLESGGGLVQPGGSLRLSCAASGWTFSDFYMEWVRQAPGKGLEWV Petition 870250103709, dated 12 / 11 / 2025, pp. 141 / 179 134 / 170 AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 54 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDNYMEWVRQAPGKGLEWV AASRNKANDYTNEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 55 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFYMEWVRQAPGKGLEWV AASRNAANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDLWGQGTLVTVSS 56 EVQLLESGGGLVQPGGSLRLSCAASGFTASDFYMEWVRQAPGKGLEWV AASRNKANDQTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDSWGQGTLVTVSS 57 EVQLLESGGGLVQPGGSLRLSCAASGFTFNDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 58 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMEWVRQAPGKGLEWV AASRNSGNSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 59 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYIEWVRQAPGKGLEWVA ASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 60 EVQLLESGGGLVQPGGSLRLSCAASGFTSSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 61EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGQSYWYFDVWGQGTLVTVSS 62 EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 63 EVQLLESGGGLVQPGGSLRLSCAASGGTFSDFYMEWVRQAPGKGLEWV AASRNKANTYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 64 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDAYMEWVRQAPGKGLEWV AASRNKANSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 65 EVQLLESGGGLVQPGGSLRLSCAASGFTQSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS Petição 870250103709, de 12 / 11 / 2025, pág. 142 / 179 135 / 170 66 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 67 EVQLLESGGGLVQPGGSLRLSCAASGDTFSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 68 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 69 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDDYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 70 EVQLLESGGGLVQPGGSLRLSCAASGFTTSDFYMEWVRQAPGKGLEWV AASRNKANSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 71 EVQLLESGGGLVQPGGSLRLSCAASGETFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 72 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 73 EVQLLESGGGLVQPGGSLRLSCAASGDTFSDFYMEWVRQAPGKGLEWVAASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 74 EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRGKGNSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSTWYFDVWGQGTLVTVSS 75 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYESSYWYFDVWGQGTLVTVSS 76 EVQLLESGGGLVQPGGSLRLSCAASGFPFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 77 EVQLLESGGGLVQPGGSLRLSCAASGFTFEDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 78 EVQLLESGGGLVQPGGSLRLSCAASGATFSDFYVEWVRQAPGKGLEWVA ASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA Petição 870250103709, de 12 / 11 / 2025, pág. 143 / 179 136 / 170 RDYYGSSYWYFDVWGQGTLVTVSS 79 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGNSYWYFDVWGQGTLVTVSS 80 EVQLLESGGGLVQPGGSLRLSCAASGFTQSDFYMEWVRQAPGKGLEWV AAIRNKANSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 81 EVQLLESGGGLVQPGGSLRLSCAASGGTFSDFYMEWVRQAPGKGLEWV AASRNKANSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 82 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSTWYFDVWGQGTLVTVSS 83 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYIIIYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSHWYFDVWGQGTLVTVSS 84 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKGNSYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 85 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDSWGQGTLVTVSS 86 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWVAASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGDSYWYFDVWGQGTLVTVSS 87 EVQLLESGGGLVQPGGSLRLSCAASGFTDSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 88 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYNDVWGQGTLVTVSS 89 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 90 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKGNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 91 EVQLLESGGGLVQPGGSLRLSCAASGFGFSDFYMEWVRQAPGKGLEWV Petição 870250103709, de 12 / 11 / 2025, pág. 144 / 179 137 / 170 GASRNKHNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 92 EVQLLESGGGLVQPGGSLRLSCAASGDTFSDFYMEWVRQAPGKGLEWV AASRNKANAYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGQSYWYFDVWGQGTLVTVSS 93 EVQLLESGGGLVQPGGSLRLSCAASGNTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 94 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKFNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 95 EVQLLESGGGLVQPGGSLRLSCAASGFPFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSPYWYFDVWGQGTLVTVSS 96 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDSYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 97 EVQLLESGGGLVQPGGSLRLSCAASGDTFSDFYLEWVRQAPGKGLEWVA ASRNKANGYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYHSSYWYFDVWGQGTLVTVSS 98 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYYDVWGQGTLVTVSS 99EVQLLESGGGLVQPGGSLRLSCAASGFTHSDFYMEWVRQAPGKGLEWV AASRNKANGYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDSWGQGTLVTVSS 100 EVQLLESGGGLVQPGGSLRLSCAASGFLFSDFYMEWVRQAPGKGLEWV AASRNKANDYIIIYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSHYWYFDVWGQGTLVTVSS 101 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANEYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 102 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKNNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 103 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANLYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSTWYFDVWGQGTLVTVSS Petição 870250103709, de 12 / 11 / 2025, pág. 145 / 179 138 / 170 104 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMEWVRQAPGKGLEWV AASRGKGNSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 105 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKGNSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 106 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDIYGSSYWYFDVWGQGTLVTVSS 107 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANTYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYDDVWGQGTLVTVSS 108 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNNANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 109 EVQLLESGGGLVQPGGSLRLSCAASGFTNSDFYMEWVRQAPGKGLEWV AASRNKFNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 110 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 111 EVQLLESGGGLVQPGGSLRLSCAASGQTFSDFYMEWVRQAPGKGLEWVAASRNKANGYTTEYTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 112 EVQLLESGGGLVQPGGSLRLSCAASGFTASDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 113 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDPYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSPYWYFDVWGQGTLVTVSS 114 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDTWGQGTLVTVSS 115 EVQLLESGGGLVQPGGSLRLSCAASGFTQSDFYMEWVRQAPGKGLEWV AASRNKANAYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGYSYWYFDVWGQGTLVTVSS 116 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDEYMEWVRQAPGKGLEWV AASRNSGNSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC Petição 870250103709, de 12 / 11 / 2025, pág. 146 / 179 139 / 170 ARDYYGSSYWYFDVWGQGTLVTVSS 117 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSQWYFDVWGQGTLVTVSS 118 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDDYMEWVRQAPGKGLEWV AATRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDSWGQGTLVTVSS 119 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNKANDYTVEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 120 EVQLLESGGGLVQPGGSLRLSCAASGFGFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 121 EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRNSGNSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYFGSSYWYFDVWGQGTLVTVSS 122 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDEYMEWVRQAPGKGLEWV AASRNKANDFTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDFYGSSYWYFDVWGQGTLVTVSS 123 EVQLLESGGGLVQPGGSLRLSCAASGFQFSDFYMEWVRQAPGKGLEWV AASRNKGNSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 124 EVQLLESGGGLVQPGGSLRLSCAASGTTFSDFYMEWVRQAPGKGLEWVAASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 125 EVQLLESGGGLVQPGGSLRLSCAASGFGFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYHDVWGQGTLVTVSS 126 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSHWYFDVWGQGTLVTVSS 127 EVQLLESGGGLVQPGGSLRLSCAASGPTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 128 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDPWGQGTLVTVSS 129 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDAYMEWVRQAPGKGLEWV Petição 870250103709, de 12 / 11 / 2025, pág. 147 / 179 140 / 170 AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSHYWYFDVWGQGTLVTVSS 130 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANDYTYEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYESSYWYFDVWGQGTLVTVSS 131 EVQLLESGGGLVQPGGSLRLSCAASGDTFSDFYMEWVRQAPGKGLEWV AASRNKANDYSTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 132 EVQLLESGGGLVQPGGSLRLSCAASGFTFSEFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 133 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRSKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSQYWYFDVWGQGTLVTVSS 134 EVQLLESGGGLVQPGGSLRLSCAASGFHFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 135 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKANDYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 136 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNTANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 137EVQLLESGGGLVQPGGSLRLSCAASGITFSDFYMEWVRQAPGKGLEWVA ASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 138 EVQLLESGGGLVQPGGSLRLSCAASGFGFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYSSSYWYFDVWGQGTLVTVSS 139 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANDYNTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 140 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYVEWVRQAPGKGLEWVA ASRNKANTYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 141 EVQLLESGGGLVQPGGSLRLSCAASGFQFSDFYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS Petição 870250103709, de 12 / 11 / 2025, pág. 148 / 179 141 / 170 142 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEVADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSNWYFDVWGQGTLVTVSS 143 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYNDVWGQGTLVTVSS 144 EVQLLESGGGLVQPGGSLRLSCAASGSTFSDFYMEWVRQAPGKGLEWV AASRNKANDFTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 145 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYFSSYWYFDVWGQGTLVTVSS 146 EVQLLESGGGLVQPGGSLRLSCAASGFTTSDFYMEWVRQAPGKGLEWV AASRNKANGYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 147 EVQLLESGGGLVQPGGSLRLSCAASGFTNSDFYMEWVRQAPGKGLEWV AASRNKANDYTTELADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 148 EVQLLESGGGLVQPGGSLRLSCAASGETFSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 149 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWVAASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYDSSYWYFDVWGQGTLVTVSS 150 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNKNNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGASYWYFDVWGQGTLVTVSS 151 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKGNDYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYFGSSYWYFDVWGQGTLVTVSS 152 EVQLLESGGGLVQPGGSLRLSCAASGFTQSDFYMEWVRQAPGKGLEWV AASRNKGNSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 153 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKANSYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 154 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AASRNKANFYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC Petição 870250103709, de 12 / 11 / 2025, pág. 149 / 179 142 / 170 ARDHYGSSYWYFDVWGQGTLVTVSS 155 EVQLLESGGGLVQPGGSLRLSCAASGFSFSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 156 EVQLLESGGGLVQPGGSLRLSCAASGFTESDFYMEWVRQAPGKGLEWV AASRNKYNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 157 EVQLLESGGGLVQPGGSLRLSCAASGFTFDDFYMEWVRQAPGKGLEWV AASRNEANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 158 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 159 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYIEWVRQAPGKGLEWVA ASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 160 EVQLLESGGGLVQPGGSLRLSCAASGFTQSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGESYWYFDVWGQGTLVTVSS 161 EVQLLESGGGLVQPGGSLRLSCAASGPTFSDFYMEWVRQAPGKGLEWV AASRNKANGYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 162 EVQLLESGGGLVQPGGSLRLSCAASGFTDSDFYMEWVRQAPGKGLEWVAASRNKANGYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 163 EVQLLESGGGLVQPGGSLRLSCAASGDTFSDFYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 164 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYLSSYWYFDVWGQGTLVTVSS 165 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGYMEWVRQAPGKGLEWV AAIRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSHYWYFDVWGQGTLVTVSS 166 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKGNDYTTAYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 167 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV Petição 870250103709, de 12 / 11 / 2025, pág. 150 / 179 143 / 170 AASRNVANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 168 EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 169 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDQYMEWVRQAPGKGLEWV AASRNKANDWTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 170 EVQLLESGGGLVQPGGSLRLSCAASGNTFSDFYMEWVRQAPGKGLEWV AASRNKANYYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 171 EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSPYWYFDVWGQGTLVTVSS 172 EVQLLESGGGLVQPGGSLRLSCAASGFTSSDFYLEWVRQAPGKGLEWVA ASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDYYGSSYWYFDVWGQGTLVTVSS 173 EVQLLESGGGLVQPGGSLRLSCAASGFTFSPFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 174 EVQLLESGGGLVQPGGSLRLSCAASGFTASDFYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDIYGSSYWYFDVWGQGTLVTVSS 175EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYLSSYWYFDVWGQGTLVTVSS 176 EVQLLESGGGLVQPGGSLRLSCAASGFTTSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDYWGQGTLVTVSS 177 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDFYGSSYWYFDVWGQGTLVTVSS 178 EVQLLESGGGLVQPGGSLRLSCAASGFTGSDFYMEWVRQAPGKGLEWV AASRNKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 179 EVQLLESGGGLVQPGGSLRLSCAASGNTFSDFYMEWVRQAPGKGLEWV AASRNKWNDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS Petição 870250103709, de 12 / 11 / 2025, pág. 151 / 179 144 / 170 180 EVQLLESGGGLVQPGGSLRLSCAASGFTFSDHYMEWVRQAPGKGLEWV AASRWKANDYTTEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDYYGSSYWYFDVWGQGTLVTVSS 181 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAEFYSYPL TFGGGTKVEIK 182 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNREIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFYSYPL TFGGGTKVEIK 183 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASHRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYAYPL TFGGGTKVEIK 184 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYPL TFGGGTKVEIK 185 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASSLQIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYPL TFGGGTKVEIK 186 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYHYP LTFGGGTKVEIK 187 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYHGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYP LTFGGGTKVEIK 188DIQMTQSPSSLSASVGDRVTITCVASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYPL TFGGGTKVEIK 189 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYQYPL TFGGGTKVEIK 190 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYYYPL TFGGGTKVEIK 191 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGSSNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYAYPL TFGGGTKVEIK 192 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRFIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYYYPL Petição 870250103709, de 12 / 11 / 2025, pág. 152 / 179 145 / 170 TFGGGTKVEIK 193 DIQMTQSPSSLSASVGDRVTITCRASESISSSKNKVHYLAWYQQKPGKAP KLLIYGASNRYYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYP LTFGGGTKVEIK 194 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGAANRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYVYPL TFGGGTKVEIK 195 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCGQFYSYPL TFGGGTKVEIK 196 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYVGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYP LTFGGGTKVEIK 197 DIQMTQSPSSLSASVGDRVTITCTASESLYSAKHKVHYLAWYQQKPGKAP KLLIYGSSNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYDYPL TFGGGTKVEIK 198 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYDGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYP LTFGGGTKVEIK 199 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVNYLAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYQYPL TFGGGTKVEIK 200 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYVAWYQQKPGKAP KLLIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYYYPL TFGGGTKVEIK 201DIQMTQSPSSLSASVGDRVTITCTASFSLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYPGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYYYP LTFGGGTKVEIK 202 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGAVNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYRYPL TFGGGTKVEIK 203 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNGYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYTYPL TFGGGTKVEIK 204 DIQMTQSPSSLSASVGDRVTITCTASESLYGSKHKVHYLAWYQQKPGKAP KLLIYGASNRYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYP LTFGGGTKVEIK 205 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP Petição 870250103709, de 12 / 11 / 2025, pág. 153 / 179 146 / 170 KLLIYGASNLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYPL TFGGGTKVEIK 206 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYFGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYP LTFGGGTKVEIK 207 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYYYP LTFGGGTKVEIK 208 DIQMTQSPSSLSASVGDRVTITCRASESISSSKHKHYLAWYQQKPGKAPKL LIYGASNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYVYPLTF GGGTKVEIK 209 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRYFGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYQYP LTFGGGTKVEIK 210 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGLSNRYIGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYSYPL TFGGGTKVEIK 211 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYWYP LTFGGGTKVEIK 212 DIQMTQSPSSLSASVGDRVTITCTASESLYSSKHKVHYLAWYQQKPGKAP KLLIYGASNRQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCAQFYAYP LTFGGGTKVEIK 213 DIQMTQSPSSLSASVGDRV...

Claims

1 / 19 CLAIMS 1. Antibody that binds specifically to phosphocholine (PC), wherein the antibody is characterized in that it comprises: a VH comprising the amino acid sequences CDRH1, CDRH2 and CDRH3 of any of the VH amino acid sequences set forth in SEQ ID NOs: 1180; and a VL comprising the amino acid sequences CDRL1, CDRL2 and CDRL3 of any of the VL amino acid sequences set forth in SEQ ID NOs: 181-368.

2. Antibody, according to claim 1, wherein the antibody is characterized in that it comprises the amino acid sequences CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 of the amino acid sequences VH and VL, respectively, established in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; 8 and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; 16 and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; 21 and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 and 212; 31 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; 35 and 184; 36 and 184; 35 and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; 9 and 224; 40 and 184; 41 and 225; 8 and 226; 42 and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8 and 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243;54 and 184; 55 and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248; 60 and 249; 8 and 250; 61 and 184; 35 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; 35 and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265; 76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; 83 and 271; 84 and 272; 1 and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; 87 and 269; 88 and 280; 89 and 269; 60 and 281; 90 and 269; 91 and 282; 22 and 283; 92 and 269; 93 and 284; 94 and 285; 95 and 286; 96 and 269; 73 and 287; 97 and 288; 68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; 4 and 289; 101 and 284; 66 and 289; 89 and 293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; 66 and 269; 108 and 299; 109 and 300; 110 and 301; Petition 870250082980, dated 09 / 15 / 2025, pp. 311 / 331 2 / 19 111 and 302; 112 and 269; 113 and 303; 1 and 304; 72 and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309;119 and 310; 120 and 311; 121 and 269; 122 and 312; 123 and 289; 9 and 313; 124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317; 127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324; 132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330; 138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 and 333; 143 and 334; 144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 and 354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 and 363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368.

3. Antibody, according to claim 1 or 2, wherein the antibody is characterized in that it comprises the amino acid sequences CDRH1, CDRH2, and CDRH3, respectively, set forth in the SEQ ID NOs: 369, 428, and 484; 370, 429, and 485; 371, 428, and 486; 372, 428, and 484; 373, 429, and 484; 374, 430, and 484; 375, 428, and 487; 376, 428, and 484; 377, 428, and 484; 378, 428, and 484; 379, 428, and 484; 372, 428, and 488; 376, 431 and 484; 380, 432 and 484; 372, 428 and 489; 381, 428 and 490; 382, 428 and 484; 381, 428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381, 428 and 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484;393, 428 and 498; 376, 428 and 495; 369, 440 and 484; 397, 428 and 484; 389, 447 and 484; 398, 448 and 492; 373, 449 and 490; 399, 428 and 484; 400, 450 and 484; 401, 428 and 484; 390, 428 and 484; 400, 428 and 499; 384, 429 and 484; 402, 436 and 484; 381, 451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and Petition 870250082980, dated 09 / 15 / 2025, pp. 312 / 331 3 / 19 500; 376, 452 and 501; 407, 428 and 484; 375, 428 and 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489; 374, 434 and 484; 411, 460 and 505; 383, 428 and 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484;413, 459 and 484; 369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484; 369, 452 and 509; 388, 468 and 490; 377, 440 and 484; 370, 428 and 484; 384, 467 and 487; 392, 469 and 510; 378, 464 and 484; 416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381, 428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484; 370, 428 and 514; 369, 475 and 484; 421, 436 and 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, ​​434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520; 417, 460 and 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484;384, 428 and 489; 426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or 400, 452 and 484.

4. Antibody, according to any of the preceding claims, wherein the antibody is characterized in that it comprises the amino acid sequences CDRL1, CDRL2 and CDRL3, respectively, set forth in the SEQ ID NOs: 523, 591 and 656; 523, 592 and 657; 523, 593 and 658; 523, 591 and 659; 523, 594 and 659; 523, 595 and 660; 523, 596 and 659; 524, 591 and 659; 523, 591 and 661; 523, 591 and 662; 523, 597 and 658; 523, 598 and 662; 525, 599 and 659; 523, 600 and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531, 591 and 663; 523, 608 and 661; 523, 610 Petition 870250082980, dated 09 / 15 / 2025, pp. 313 / 331 4 / 19 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659;534, 619 and 662; 535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659; 523, 617 and 659; 523, 623 and 659; 538, 607 and 672; 523, 616 and 671; 523, 624 and 659; 523, 620 and 659; 523, 625 and 660; 523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661; 523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676; 555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 and 659;523, 592 and 670; 560, 591 and 667; 530, 591 and 659; 561,603 and 666; 562, 591 and 659; 523, 616 and 660; 523, 602 and 677; 523, 616 and 659; 523, 630 and 660; 563, 591 and 659; 523, 640 and 659; 564, 591 and 659; 523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571, 630 and 663; 572, 591 and 664; 573, 591 and 670; 523, 646 and 659; 574, 591 and 670; 523, 647 and 667; 575, 591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660; 527, 591 and 659; 581, 595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659;560, 591 and 659; 580, 606 and 659; 589, 593 and 661; 523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672; 523, 626 and 668; 523, 655 and 659; or 523, 606 and 680.

5. Antibody, according to any of the preceding claims in Petition 870250082980, dated 09 / 15 / 2025, pp. 314 / 331 5 / 19, wherein the antibody is characterized in that it comprises the amino acid sequences CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3, set forth in SEQ ID Nos: 369, 428, 484, 523, 591 and 656; 370, 429, 485, 523, 592 and 657; 371, 428, 486, 523, 593 and 658; 372, 428, 484, 523, 591 and 659; 373, 429, 484, 523, 594 and 659; 369, 428, 484, 523, 591 and 659; 374, 430, 484, 523, 591 and 659; 369, 428, 484, 523, 595 and 660; 375, 428, 487, 523, 596 and 659; 376, 428, 484, 524, 591 and 659; 377, 428, 484, 523, 591 and 661; 378, 428, 484, 523, 591 and 662; 372, 428, 484, 523, 597 and 658; 379, 428, 484, 523, 598 and 662; 372, 428, 488, 525, 599 and 659; 376, 431, 484, 523, 600 and 663; 380, 432, 484, 523, 591 and 664; 372, 428, 489, 523, 601 and 659; 381,428, 490, 523, 591 and 659; 382, 428, 484, 526, 597 and 665; 381,428, 491,523, 602 and 659; 369, 428, 484, 527, 591 and 661; 377, 428, 492, 528, 591 and 662;376, 433, 484, 529, 603 and 662; 383, 434, 484, 523, 604 and 666; 383, 428, 484, 523, 605 and 667; 384, 435, 484, 530, 606 and 659; 369, 436, 484, 523, 607 and 659; 372, 437, 487, 523, 591 and 659; 372, 428, 484, 523, 608 and 659; 385, 428, 493, 523, 609 and 662; 386, 428, 484, 531, 591 and 663; 372, 437, 484, 523, 608 and 661; 377, 428, 484, 523, 610 and 659; 387, 428, 484, 523, 611 and 668; 385, 428, 484, 523, 611 and 658; 372, 438, 484, 523, 596 and 662; 388, 428, 494, 523, 612 and 667; 369, 439, 484, 523, 613 and 668; 389, 428, 484, 523, 591 and 669; 382, ​​428, 484, 523, 591 and 663; 369, 428, 484, 523, 614 and 659; 381, 428, 484, 523, 591 and 659; 376, 440, 495, 523, 591 and 659; 381, 428, 484, 532, 615 and 662; 381, 428, 484, 523, 616 and 670; 390, 441, 484, 523, 591 and 659; 370, 442, 484, 523, 591 and 668; 391, 428, 484, 523, 617 and 671; 377, 428, 484, 533, 595 and 659; 377, 428, 484, 523, 618 and 659; 392, 432, 484, 523, 591 and 659; 377, 443, 484, 534, 619 and 662; 376, 428, 484, 535, 620 and 659; 393, 428, 484, 536, 621 and 659;381, 428, 484, 537, 603 and 671; 383, 444, 489, 523, 622 and 59; 372, 428, 484, 523, 617 and 659; 377, 428, 484, 523, 623 and 659; 376, 428, 484, 538, 607 and 672; 369, 428, 484, 523, 616 and 671; 376, 428, 484, 523, 624 and 659; 394, 428, 484, 523, 591 and 659; 369, 428, 484, 523, 620 and 659; 383, 444, 496, 523, 625 and 660; 385, 428, 484, 523, 602 and 671; 376, 434, 484, 523, 591 and 659; 395, 445, 497, 523, 611 and 663; 396, 446, 487, 523, 626 and 670; 369, 428, 484, 523, 617 and 659; 392, 428, 484, 523, 591 and 662; 394, 428, 484, 523, 606 and 673; 393, 428, 498, 523, 591 and 659; 376, 428, 495, 523, 627 and 671; 369, 440, 484, 523, 628 and Petition 870250082980, dated 09 / 15 / 2025, pp. 315 / 331 6 / 19 671; 397, 428, 484, 539, 591 and 662; 389, 447, 484, 523, 591 and 659; 398, 448, 492, 523, 591 and 670; 373, 449, 490, 523, 611 and 659; 399, 428, 484, 537, 613 and 671; 400,450, 484, 540, 598 and 659; 401, 428, 484, 541, 591 and 659; 390, 428, 484, 542, 629 and 659; 376, 428, 484, 523, 591 and 671; 400, 428, 499, 523, 591 and 659;381, 428, 484, 523, 630 and 667; 384, 429, 484, 543, 631 and 659; 369, 428, 484, 523, 632 and 664; 402, 436, 484, 523, 597 and 661; 381, 451, 484, 523, 591 and 656; 403, 428, 484, 523, 633 and 659; 369, 429, 484, 544, 607 and 659; 404, 429, 484, 523, 630 and 659; 372, 429, 484, 523, 602 and 659; 381, 428, 484, 523, 591 and 665; 388, 428, 484, 523, 610 and 674; 405, 451, 484, 523, 634 and 671; 406, 428, 484, 545, 591 and 661; 400, 428, 484, 523, 635 and 667; 404, 428, 484, 546, 591 and 659; 384, 432, 500, 523, 636 and 664; 376, 452, 501, 547, 591 and 663; 407, 428, 484, 548, 619 and 659; 375, 428, 484, 523, 637 and 659; 372, 428, 484, 523, 607 and 659; 408, 428, 484, 523, 638 and 659; 386, 428, 484, 523, 591 and 659; 369, 428, 497, 523, 591 and 659; 403, 453, 484, 549, 591 and 659; 402, 454, 484, 523, 591 and 659; 383, 428, 484, 523, 591 and 659; 383, 434, 500, 523, 591 and 659; 376, 455, 502, 550, 591 and 675; 383, 435, 484, 523, 591 and 664; 369, 428, 484, 523, 602 and 659; 376, 428, 484, 551, 591 and 659; 376, 428, 484, 552, 591 and 659;383, 428, 484, 553, 591 and 676; 376,428, 484, 554, 591 and 659; 376, 428, 490, 523, 591 and 676; 369, 428, 503, 555, 606 and 659; 409, 428, 484, 523, 591 and 659; 383, 428, 504, 556, 591 and 659; 369, 434, 484, 523, 591 and 659; 390, 428, 484, 523, 637 and 677; 369, 456, 484, 523, 591 and 659; 370, 457,484, 557, 591 and 659; 383, 428, 484, 558, 591 and 659; 404, 458, 499, 523, 591 and 659; 410, 428, 484, 523, 591 and 677; 383, 459, 484, 553, 639 and 659; 407, 428, 489, 549, 591 and 667; 374, 434, 484, 523, 591 and 659; 404, 428, 484, 559, 617 and 666; 411, 460, 505, 523, 591 and 672; 372, 429, 484, 523, 606 and 659; 383, 428, 485, 523, 591 and 659; 386, 460, 490, 523, 601 and 659; 412, 455, 493, 523, 592 and 670; 372, 428, 484, 560, 591 and 667; 372, 428, 484, 523, 606 and 659; 383, 461, 484, 523, 591 and 677; 369, 429, 484, 523, 606 and 659; 369, 434, 484, 530, 591 and 659; 376, 437, 484, 561, 603 and 666; 383, 462, 500, 523, 591 and 659; 383, 428, 484, 562, 591 and 659; 400, 463, 484, 523, 616 and 660; 376, 464, 484, 523, 602 and 677;400, 434, 506, 549, 591 and 659; 369, 436, 507, 523, 591 and 659; 404, 429, 484, 523, 591 and 659; 384, 429, 484, 523, 616 and 659; 369, 429, 484, 523, 591 and 659; 377, 465, 484, 523, 630 and 660; 413, 459, 484, 563, 591 and 659; 369, 452, Petition 870250082980, dated 09 / 15 / 2025, pp. 316 / 331 7 / 19 484, 523, 591 and 663; 414, 466, 484, 523, 640 and 659; 373, 428, 484, 523, 591 and 659; 415, 428, 489, 564, 591 and 659; 369, 428, 484, 523, 591 and 671; 400, 428, 484, 523, 641 and 677; 369, 428, 491, 565, 591 and 662; 403, 458, 508, 523, 642 and 664; 392, 467, 484, 523, 591 and 659; 369, 452, 509, 566, 643 and 659; 388, 468, 490, 523, 591 and 659; 369, 452, 484, 523, 644 and 667; 377, 440, 484, 567, 606 and 659; 370, 428, 484, 523, 591 and 656; 384, 467, 487, 523, 591 and 659; 392, 469, 510, 568, 591 and 659; 378, 464, 484, 523, 606 and 659; 377, 428, 484, 569, 645 and 659; 416, 434, 484, 523, 603 and 659; 370, 428, 484, 523, 606 and 659; 370, 428, 511, 570, 628 and 678; 369, 452, 484, 571, 630 and 663; 376, 428, 502, 572, 591 and 664;417, 428, 484, 523, 591 and 665; 392, 428, 484, 573, 591 and 670; 376, 428, 512, 523, 646 and 659; 377, 428, 484, 574, 591 and 670; 383, 428, 484, 523, 647 and 667; 381, 428, 493, 575, 591 and 659; 383, 470, 501, 523, 591 and 659; 404, 471, 484, 537, 591 and 659; 418, 428, 484, 523, 635 and 670; 383, 472, 513, 576, 591 and 659; 419, 428, 484, 577, 606 and 659; 397, 428, 484, 523, 648 and 679; 372, 473, 484, 523, 591 and 664; 383, 474, 484, 523, 592 and 659; 372, 428, 484, 523, 591 and 663; 420, 434, 484, 523, 595 and 659; 370, 428, 514, 523, 591 and 659; 369, 428, 484, 523, 591 and 677; 383, 428, 484, 523, 600 and 659; 369, 475, 484, 523, 591 and 659; 421, 436, 484, 523, 649 and 664; 378, 452, 484, 523, 591 and 659; 376, 476, 515, 578, 641 and 659; 376, 428, 504, 523, 591 and 667; 422, 469, 484, 523, 606 and 660; 383, 461, 484, 523, 616 and 659; 369, 428, 484, 523, 650 and 656; 369, 428, 516, 523, 591 and 659; 405, 460, 484, 523, 618 and 659; 413, 431, 484, 523, 591 and 659; 382, ​​428, 484, 579, 621 and 671; 383, 428, 484, 523, 646 and 659;372, 428, 484, 580, 591 and 660; 406, 429, 484, 527, 591 and 659; 383,428, 517, 581, 595 and 659; 377, 437, 518, 582, 640 and 664; 369, 477, 487, 583, 651 and 659; 403, 464, 484, 534, 591 and 659; 383, 459, 484, 523, 606 and 659; 369, 454, 484, 584, 591 and 671; 372, 478, 519, 523, 591 and 680; 423, 429, 484, 523, 591 and 681; 383, 428,484, 585, 591 and 659; 369, 434, 484, 557, 591 and 659; 382, 434, 484, 523, 649 and 659;424, 479, 484, 523, 616 and 660; 376, 429, 484, 586, 591 and 666; 425, 428, 484, 523, 592 and 659; 369, 436, 484, 587, 652 and 659; 403, 428, 520, 588, 638 and 659; 417, 460, 484, 523, 591 and 659; 409, 460, 484, 523, 623 and 664; 404, 452, 484, 523, 591 and 659; 369, 428, 484, 523, 591 and 682; 383, 428, 521, 553, 653 and 659; 372, 480, 493, 523, 591 and 659; 369, 428, 484, 523, 654 and 659; 369, 477, 484, 523, 648 and 659; 369, 481, 484, 560, 591 Petition 870250082980, dated 09 / 15 / 2025, pp. 317 / 331 8 / 19 and 659; 369, 452, 484, 523, 591 and 667; 409, 428, 484, 580, 606 and 659; 384, 452, 484, 589, 593 and 661;377, 482, 484, 523, 591 and 659; 410, 483, 484, 523, 591 and 659; 384, 428, 489, 523, 591 and 659; 426, 429, 484, 523, 622 and 659; 376, 428, 484, 523, 637 and 676; 427, 428, 484, 523, 591 and 671; 373, 452, 506, 523, 591 and 659; 369, 428, 484, 590, 622 and 659; 369, 429, 521, 555, 591 and 661; 405, 428, 522, 523, 615 and 672; 376, 428, 510, 523, 591 and 659; 384, 428, 484, 523, 626 and 668; 410, 429, 484, 523, 591 and 659; 400, 452, 484, 523, 655 and 659; or 369, 434, 484, 523, 606 and 680.

6. Antibody, according to any of the preceding claims, wherein the antibody is characterized in that it comprises the amino acid sequence VH of any of the SEQ ID NOs: 1-180.

7. Antibody, according to any of the preceding claims, wherein the antibody is characterized in that it comprises the amino acid sequence VL of any of the SEQ ID NOs: 181-368.

8. Antibody, according to any of the preceding claims, characterized in that VH and VL comprise the amino acid sequences, respectively, established in the SEQ ID NOs: 1 and 181; 2 and 182; 3 and 183; 4 and 184; 5 and 185; 1 and 184; 6 and 184; 1 and 186; 7 and 187; 8 and 188; 9 and 189; 10 and 190; 4 and 191; 11 and 192; 12 and 193; 13 and 194; 14 and 195; 15 and 196; 16 and 184; 17 and 197; 18 and 198; 1 and 199; 19 and 200; 20 and 201; 21 and 202; 22 and 203; 23 and 204; 24 and 205; 25 and 184; 4 and 206; 26 and 207; 27 and 208; 28 and 209; 9 and 210; 29 and 211; 30 and 212; 31 and 213; 32 and 214; 33 and 215; 34 and 216; 17 and 217; 1 and 218; 35 and 184; 36 and 184; 35 and 219; 35 and 220; 37 and 184; 38 and 221; 39 and 222; 9 and 223; 9 and 224; 40 and 184; 41 and 225; 8 and 226; 42 and 227; 35 and 228; 43 and 229; 4 and 230; 9 and 231; 8 and 232; 1 and 233; 8 and 234; 44 and 184; 1 and 235; 45 and 236; 30 and 237; 46 and 184; 47 and 238; 48 and 239; 1 and 230; 49 and 190; 44 and 240; 50 and 184; 51 and 241; 52 and 242; 53 and 243; 54 and 184; 55 and 244; 56 and 245; 57 and 246; 58 and 247; 59 and 248;60 and 249; 8 and 250; 61 and 184; 35 and 251; 62 and 252; 1 and 253; 63 and 254; 64 and 181; 65 and 255; 66 and 256; 67 and 257; 68 and 198; 35 and 258; 69 and 259; 70 and 260; 71 and 261; 72 and 262; 73 and 263; 74 and 264; 75 and 265; 76 and 266; 77 and 267; 4 and 205; 78 and 268; 1 and 269; 27 and 269; 79 and 269; 80 and 270; 81 and 269; 22 and 269; 82 and 269; 83 and 271; 84 and 272; 1 and 273; 8 and 274; 8 and 275; 22 and 276; 8 and 277; 85 and 278; 86 and 279; 87 and 269; 88 and 280; 89 and 269; Petition 870250082980, dated 09 / 15 / 2025, pp. 318 / 331 9 / 19 60 and 281; 90 and 269; 91 and 282; 22 and 283; 92 and 269; 93 and 284; 94 and 285; 95 and 286; 96 and 269; 73 and 287; 97 and 288; 68 and 289; 98 and 269; 99 and 290; 100 and 291; 4 and 292; 4 and 289; 101 and 284; 66 and 289; 89 and 293; 102 and 294; 103 and 269; 22 and 295; 104 and 296; 105 and 297; 106 and 270; 107 and 269; 67 and 269; 62 and 298; 66 and 269; 108 and 299; 109 and 300; 110 and 301; 111 and 302; 112 and 269; 113 and 303; 1 and 304; 72 and 305; 114 and 306; 115 and 307; 116 and 269; 117 and 308; 118 and 269; 110 and 309; 119 and 310; 120 and 311; 121 and 269; 122 and 312; 123 and 289; 9 and 313;124 and 314; 120 and 289; 125 and 315; 110 and 316; 126 and 317; 127 and 318; 49 and 319; 128 and 320; 9 and 321; 22 and 322; 129 and 323; 130 and 269; 131 and 324; 132 and 325; 133 and 326; 134 and 327; 53 and 328; 135 and 272; 136 and 329; 4 and 301; 137 and 330; 138 and 269; 1 and 284; 22 and 331; 139 and 269; 140 and 332; 141 and 269; 142 and 333; 143 and 334; 144 and 335; 101 and 298; 1 and 336; 145 and 269; 146 and 337; 147 and 269; 17 and 338; 22 and 320; 4 and 339; 148 and 340; 149 and 341; 150 and 342; 151 and 343; 152 and 344; 94 and 289; 153 and 345; 154 and 346; 155 and 347; 22 and 348; 89 and 282; 156 and 349; 157 and 296; 158 and 350; 159 and 329; 24 and 351; 160 and 352; 161 and 269; 162 and 353; 163 and 269; 1 and 354; 164 and 355; 165 and 269; 1 and 356; 166 and 357; 167 and 358; 110 and 334; 87 and 359; 168 and 360; 169 and 269; 170 and 269; 171 and 269; 172 and 361; 8 and 362; 173 and 304; 174 and 269; 1 and 363; 175 and 364; 176 and 365; 177 and 269; 178 and 366; 179 and 269; 180 and 367; or 89 and 368.

9. Antibody, according to any of the preceding claims, wherein the antibody is characterized by the fact that it contains a variable single-chain fragment (scFv).

10. Antibody, according to any one of claims 1 to 8, wherein the antibody is characterized in that it comprises a constant heavy chain region, or an Fc region thereof, optionally selected from the group consisting of human IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2.

11. Antibody, according to claim 10, characterized in that the constant region of the heavy chain is a human IgG1.

12. Antibody, according to claim 10, characterized in that the constant region of the heavy chain is a human IgG4.

13. Antibody, according to claim 12, characterized in that the amino acid sequence of the constant region of the heavy chain of human IgG4 comprises a P at position 228, numbered according to the EU numbering system.

14. Antibody, according to any one of claims 10 to 13, characterized in that the constant region of the heavy chain is a variant of a wild-type constant region of the heavy chain, wherein the variant constant region of the heavy chain binds to an Fc gamma receptor (FcyR) with lower affinity than the wild-type constant region of the heavy chain binds to FcyR.

15. Antibody, according to claim 14, characterized in that the amino acid sequence of the constant region of the heavy chain comprises: A at position 234; A at position 235; A, Q or G at position 297; or A or G at position 329, in each case numbered according to the EU numbering system.

16. Antibody, according to claim 14, characterized in that the amino acid sequence of the constant region of the heavy chain comprises: A at positions 234 and 235; A at positions 234, 235 and 329; or A at positions 234, 235 and G at position 329, in each case numbered according to the EU numbering system.

17. Antibody, according to any one of claims 10 to 16, characterized in that the constant region of the heavy chain is a variant of a wild-type constant region of the heavy chain, and wherein the variant constant region of the heavy chain has an increased affinity for the human neonatal Fc receptor (FcRn) at pH 6 compared to the affinity of the wild-type constant region of the heavy chain for human FcRn at pH 6.

18. Antibody according to claim 17, characterized in that the amino acid sequence of the constant region of the heavy chain comprises: L and S at positions 428 and 434, respectively; K, F and Y at positions 433, 434 and 436, respectively; or Y, T and E at positions 252, 254 and 256, respectively, in each case numbered according to the EU numbering system. Petition 870250082980, dated 15 / 09 / 2025, pp. 320 / 331 11 / 19 19. Antibody, according to any one of claims 1 to 18, characterized in that it comprises a constant region of the light chain, optionally a human kappa or lambda constant region.

20. Polypeptide characterized in that it comprises a VH comprising the amino acid sequences CDRH1, CDRH2 and CDRH3 of any of the VH amino acid sequences set forth in SEQ ID NOs: 1-180.

21. Polypeptide, according to claim 20, wherein the polypeptide is characterized in that it comprises the amino acid sequences CDRH1, CDRH2 and CDRH3, respectively, set forth in the SEQ ID Nos: 369, 428 and 484; 370, 429 and 485; 371, 428 and 486; 372, 428 and 484; 373, 429 and 484; 374, 430 and 484; 375, 428 and 487; 376, 428 and 484; 377, 428 and 484; 378, 428 and 484; 379, 428 and 484; 372, 428 and 488; 376, 431 and 484; 380, 432 and 484; 372, 428 and 489; 381, 428 and 490; 382, 428 and 484; 381,428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381, 428 and 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484;393, 428 and 498; 376, 428 and 495; 369, 440 and 484; 397, 428 and 484; 389, 447 and 484; 398, 448 and 492; 373, 449 and 490; 399, 428 and 484; 400, 450 and 484; 401, 428 and 484; 390, 428 and 484; 400, 428 and 499; 384, 429 and 484; 402, 436 and 484; 381, 451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and 500; 376, 452 and 501; 407, 428 and 484; 375, 428 and 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489; 374, 434 and 484; 411,460 and 505; 383, 428 and 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and Petition 870250082980, dated 09 / 15 / 2025, pp. 321 / 331 12 / 19 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484;413, 459 and 484; 369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484; 369, 452 and 509; 388, 468 and 490; 377, 440 and 484; 370, 428 and 484; 384, 467 and 487; 392, 469 and 510; 378, 464 and 484; 416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381, 428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484; 370, 428 and 514; 369, 475 and 484; 421, 436 and 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, ​​434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520; 417, 460 and 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484;384, 428 and 489; 426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or 400, 452 and 484.

22. Polypeptide, according to claim 20, characterized in that the VH comprises the amino acid sequences CDRH1, CDRH2 and CDRH3, respectively, established in the SEQ ID NOs: 369, 428 and 484; 370, 429 and 485; 371, 428 and 486; 372, 428 and 484; 373, 429 and 484; 374, 430 and 484; 375, 428 and 487; 376, 428 and 484; 377, 428 and 484; 378, 428 and 484; 379, 428 and 484; 372, 428 and 488; 376, 431 and 484; 380, 432 and 484; 372, 428 and 489; 381, 428 and 490; 382, 428 and 484; 381, 428 and 491; 377, 428 and 492; 376, 433 and 484; 383, 434 and 484; 383, 428 and 484; 384, 435 and 484; 369, 436 and 484; 372, 437 and 487; 385, 428 and 493; 386, 428 and 484; 372, 437 and 484; 387, 428 and 484; 385, 428 and 484; 372, 438 and 484; 388, 428 and 494; 369, 439 and 484; 389, 428 and 484; 381, 428 and 484; 376, 440 and 495; 390, 441 and 484; 370, 442 and 484; 391, 428 and 484; 392, 432 and 484; 377, 443 and 484; 393, 428 and 484; 383, 444 and 489; 394, 428 and 484; 383, 444 and 496; 376, 434 and 484; 395, 445 and 497; 396, 446 and 487; 392, 428 and 484; 393, 428 and 498;376, 428 and 495; 369, 440 and 484; 397, 428 and 484; 389, 447 and 484; 398, 448 and 492; 373, 449 and 490; 399, 428 and 484; 400, 450 and 484; 401, 428 and 484; 390, 428 and 484; 400, 428 and 499; 384, 429 and 484; 402, 436 and 484; 381, Petition 870250082980, dated 09 / 15 / 2025, page. 322 / 331 13 / 19 451 and 484; 403, 428 and 484; 369, 429 and 484; 404, 429 and 484; 372, 429 and 484; 388, 428 and 484; 405, 451 and 484; 406, 428 and 484; 400, 428 and 484; 404, 428 and 484; 384, 432 and 500; 376, 452 and 501; 407, 428 and 484; 375, 428 and 484; 408, 428 and 484; 369, 428 and 497; 403, 453 and 484; 402, 454 and 484; 383, 434 and 500; 376, 455 and 502; 383, 435 and 484; 376, 428 and 490; 369, 428 and 503; 409, 428 and 484; 383, 428 and 504; 369, 434 and 484; 369, 456 and 484; 370, 457 and 484; 404, 458 and 499; 410, 428 and 484; 383, 459 and 484; 407, 428 and 489; 374, 434 and 484; 411,460 and 505; 383, 428 and 485; 386, 460 and 490; 412, 455 and 493; 383, 461 and 484; 376, 437 and 484; 383, 462 and 500; 400, 463 and 484; 376, 464 and 484; 400, 434 and 506; 369, 436 and 507; 377, 465 and 484; 413, 459 and 484;369, 452 and 484; 414, 466 and 484; 373, 428 and 484; 415, 428 and 489; 369, 428 and 491; 403, 458 and 508; 392, 467 and 484; 369, 452 and 509; 388, 468 and 490; 377, 440 and 484; 370, 428 and 484; 384, 467 and 487; 392, 469 and 510; 378, 464 and 484; 416, 434 and 484; 370, 428 and 511; 376, 428 and 502; 417, 428 and 484; 376, 428 and 512; 381, 428 and 493; 383, 470 and 501; 404, 471 and 484; 418, 428 and 484; 383, 472 and 513; 419, 428 and 484; 372, 473 and 484; 383, 474 and 484; 420, 434 and 484; 370, 428 and 514; 369, 475 and 484; 421, 436 and 484; 378, 452 and 484; 376, 476 and 515; 376, 428 and 504; 422, 469 and 484; 369, 428 and 516; 405, 460 and 484; 413, 431 and 484; 406, 429 and 484; 383, 428 and 517; 377, 437 and 518; 369, 477 and 487; 403, 464 and 484; 369, 454 and 484; 372, 478 and 519; 423, 429 and 484; 382, ​​434 and 484; 424, 479 and 484; 376, 429 and 484; 425, 428 and 484; 403, 428 and 520; 417, 460 and 484; 409, 460 and 484; 404, 452 and 484; 383, 428 and 521; 372, 480 and 493; 369, 477 and 484; 369, 481 and 484; 384, 452 and 484; 377, 482 and 484; 410, 483 and 484; 384, 428 and 489;426, 429 and 484; 427, 428 and 484; 373, 452 and 506; 369, 429 and 521; 405, 428 and 522; 376, 428 and 510; 384, 428 and 484; 410, 429 and 484; or 400, 452 and 484.

23. Polypeptide, according to claim 20, characterized in that VH comprises any of the amino acid sequences set forth in SEQ ID NOs: 1-180.

24. Polypeptide characterized in that it comprises a VL comprising the amino acid sequences CDRL1, CDRL2, and CDRL3 of any of the VL amino acid sequences set forth in SEQ ID Nos: 181-368. Petition 870250082980, dated 09 / 15 / 2025, pp. 323 / 331 14 / 19 25. Polypeptide, according to claim 24, wherein the polypeptide is characterized in that it comprises the amino acid sequences CDRL1, CDRL2 and CDRL3, respectively, set forth in the SEQ ID NOs: 523, 591 and 656; 523, 592 and 657; 523, 593 and 658; 523, 591 and 659; 523, 594 and 659; 523, 595 and 660; 523, 596 and 659; 524, 591 and 659; 523, 591 and 661; 523, 591 and 662; 523, 597 and 658; 523, 598 and 662; 525, 599 and 659; 523, 600 and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531,591 and 663; 523, 608 and 661; 523, 610 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659; 534, 619 and 662; 535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659;523, 617 and 659; 523, 623 and 659; 538, 607 and 672; 523, 616 and 671; 523, 624 and 659; 523, 620 and 659; 523, 625 and 660; 523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661; 523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676; 555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 and 659; 523, 592 and 670; 560, 591 and 667; 530, 591 and 659; 561, 603 and 666; 562, 591 and 659;523, 616 and 660; 523, 602 and 677; 523, 616 and 659; 523, 630 and 660; 563, 591 and 659; 523, 640 and 659; 564, 591 and 659; 523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571, 630 and 663; 572, 591 and 664; 573, 591 and 670; 523, 646 and 659; 574, 591 and 670; 523, 647 and 667; 575, 591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 Petition 870250082980, dated 09 / 15 / 2025, pp. 324 / 331 15 / 19 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660; 527, 591 and 659; 581, 595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659; 560, 591 and 659; 580, 606 and 659;589, 593 and 661; 523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672; 523, 626 and 668; 523, 655 and 659; or 523, 606 and 680.

26. Polypeptide, according to claim 24, characterized in that the VL comprises the amino acid sequences CDRL1, CDRL2 and CDRL3, respectively, established in the SEQ ID NOs: 523, 591 and 656; 523, 592 and 657; 523, 593 and 658; 523, 591 and 659; 523, 594 and 659; 523, 595 and 660; 523, 596 and 659; 524, 591 and 659; 523, 591 and 661; 523, 591 and 662; 523, 597 and 658; 523, 598 and 662; 525, 599 and 659; 523, 600 and 663; 523, 591 and 664; 523, 601 and 659; 526, 597 and 665; 523, 602 and 659; 527, 591 and 661; 528, 591 and 662; 529, 603 and 662; 523, 604 and 666; 523, 605 and 667; 530, 606 and 659; 523, 607 and 659; 523, 608 and 659; 523, 609 and 662; 531, 591 and 663; 523, 608 and 661; 523, 610 and 659; 523, 611 and 668; 523, 611 and 658; 523, 596 and 662; 523, 612 and 667; 523, 613 and 668; 523, 591 and 669; 523, 591 and 663; 523, 614 and 659; 532, 615 and 662; 523, 616 and 670; 523, 591 and 668; 523, 617 and 671; 533, 595 and 659; 523, 618 and 659; 534, 619 and 662; 535, 620 and 659; 536, 621 and 659; 537, 603 and 671; 523, 622 and 659; 523, 617 and 659;523, 623 and 659; 538, 607 and 672; 523, 616 and 671; 523, 624 and 659; 523, 620 and 659; 523, 625 and 660; 523, 602 and 671; 523, 611 and 663; 523, 626 and 670; 523, 606 and 673; 523, 627 and 671; 523, 628 and 671; 539, 591 and 662; 523, 591 and 670; 523, 611 and 659; 537, 613 and 671; 540, 598 and 659; 541, 591 and 659; 542, 629 and 659; 523, 591 and 671; 523, 630 and 667; 543, 631 and 659; 523, 632 and 664; 523, 597 and 661; 523, 633 and 659; 544, 607 and 659; 523, 630 and 659; 523, 591 and 665; 523, 610 and 674; 523, 634 and 671; 545, 591 and 661; 523, 635 and 667; 546, 591 and 659; 523, 636 and 664; 547, 591 and 663; 548, 619 and 659; 523, 637 and 659; 523, 638 and 659; 549, 591 and 659; 550, 591 and 675; 551, 591 and 659; 552, 591 and 659; 553, 591 and 676; 554, 591 and 659; 523, 591 and 676; 555, 606 and 659; 556, 591 and 659; 523, 637 and 677; 557, 591 and 659; 558, 591 and 659; 523, 591 and 677; 553, 639 and 659; 549, 591 and 667; 559, 617 and 666; 523, 591 and 672; 523, 606 Petition 870250082980, dated 09 / 15 / 2025, pages 325 / 331 16 / 19 and 659; 523, 592 and 670; 560, 591 and 667; 530, 591 and 659;561, 603 and 666; 562, 591 and 659; 523, 616 and 660; 523, 602 and 677; 523, 616 and 659; 523, 630 and 660; 563, 591 and 659; 523, 640 and 659; 564, 591 and 659; 523, 641 and 677; 565, 591 and 662; 523, 642 and 664; 566, 643 and 659; 523, 644 and 667; 567, 606 and 659; 568, 591 and 659; 569, 645 and 659; 523, 603 and 659; 570, 628 and 678; 571, 630 and 663; 572, 591 and 664; 573, 591 and 670; 523, 646 and 659; 574, 591 and 670; 523, 647 and 667; 575, 591 and 659; 537, 591 and 659; 523, 635 and 670; 576, 591 and 659; 577, 606 and 659; 523, 648 and 679; 523, 592 and 659; 523, 595 and 659; 523, 600 and 659; 523, 649 and 664; 578, 641 and 659; 523, 591 and 667; 523, 606 and 660; 523, 650 and 656; 579, 621 and 671; 580, 591 and 660; 527, 591 and 659; 581, 595 and 659; 582, 640 and 664; 583, 651 and 659; 534, 591 and 659; 584, 591 and 671; 523, 591 and 680; 523, 591 and 681; 585, 591 and 659; 523, 649 and 659; 586, 591 and 666; 587, 652 and 659; 588, 638 and 659; 523, 623 and 664; 523, 591 and 682; 553, 653 and 659; 523, 654 and 659; 523, 648 and 659; 560, 591 and 659; 580, 606 and 659; 589, 593 and 661;523, 637 and 676; 590, 622 and 659; 555, 591 and 661; 523, 615 and 672; 523, 626 and 668; 523, 655 and 659; or 523, 606 and 680.

27. Polypeptide, according to claim 24, characterized in that the VL comprises any of the amino acid sequences set forth in SEQ ID NOS: 181-368.

28. Antibody or polypeptide, according to any of the preceding claims, wherein the antibody or polypeptide is characterized in that it is conjugated to a cytotoxic agent, cytostatic agent, toxin, radionuclide or detectable marker.

29. Polynucleotide characterized in that it encodes a VH and / or a VL of an antibody, as defined in any one of claims 1 to 19, or a polypeptide, as defined in any one of claims 20 to 27.

30. Vector characterized in that it comprises the polynucleotide as defined in claim 29.

31. Vector, according to claim 30, wherein the vector is characterized in that it is an adeno-associated virus (AAV) vector.

32. Recombinant host cell characterized by the fact of Petition 870250082980, dated 09 / 15 / 2025, pp. 326 / 331 17 / 19 comprising: (a) the polynucleotide, as defined in claim 29; (b) the vector, as defined in claim 30 or 31; (c) a first polynucleotide encoding a VH or heavy chain of the antibody, as defined in any of claims 1 to 19, and a second polynucleotide encoding a VL or light chain of the antibody, as defined in any of claims 1 to 19; or (d) a first vector comprising a first polynucleotide encoding a VH or heavy chain of the antibody, as defined in any of claims 1 to 19, and a second vector comprising a second polynucleotide encoding a VL or light chain of the antibody, as defined in any of claims 1 to 19.

33. Pharmaceutical composition characterized in that it comprises the antibody or polypeptide, as defined in any one of claims 1 to 28, the polynucleotide, as defined in claim 29, the vector, as defined in claim 30 or 31, or the host cell, as defined in claim 32, and a pharmaceutically acceptable vehicle or excipient.

34. Method for producing an antibody or polypeptide, wherein the method is characterized in that it comprises cultivating the host cell, as defined in claim 32, under suitable conditions, such that the polynucleotide is expressed and the antibody or polypeptide is produced.

35. A method for inhibiting PC activity in a subject, wherein the method is characterized in that it comprises administering to the subject an effective amount of the antibody or polypeptide, as defined in any one of claims 1 to 28, the polynucleotide, as defined in claim 29, the vector, as defined in claim 30 or 31, the host cell, as defined in claim 32, or the pharmaceutical composition, as defined in claim 33.

36. Method for treating an inflammatory disorder or degenerative disease in a subject, wherein the method is characterized in that Petition 870250082980, dated 09 / 15 / 2025, pp. 327 / 331 18 / 19 comprises administering to the subject an effective amount of the antibody or polypeptide, as defined in any of claims 1 to 28, the polynucleotide, as defined in claim 29, the vector, as defined in claim 30 or 31, the host cell, as defined in claim 32, or the pharmaceutical composition, as defined in claim 33.

37. A method according to claim 36, characterized in that the inflammatory disorder or degenerative disease is selected from the group consisting of organ reperfusion injury, such as reperfusion injury induced by myocardial infarction, Kawasaki disease, non-alcoholic steatohepatitis (NASH), organ transplant rejection, atherosclerosis, type I or type 2 diabetes, rheumatoid arthritis, osteoporosis, acute lung injury, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pain, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), stroke, Huntington's disease, frontotemporal dementia (FTD), multiple sclerosis (MS), isolated demyelinating diseases of the central nervous system, osteoarthritis, Crohn's disease, and ulcerative colitis.

38. Use of the antibody or polypeptide, as defined in any one of claims 1 to 28, of the polynucleotide, as defined in claim 29, of the vector, as defined in claim 30 or 31, of the host cell, as defined in claim 32, or of the pharmaceutical composition, as defined in claim 33, characterized in that it is for the manufacture of a medicament for the treatment of an inflammatory disorder or degenerative disease in a subject in need thereof.

39. Use, according to claim 38, characterized in that the inflammatory disorder or degenerative disease is selected from the group consisting of organ reperfusion injury, such as reperfusion injury induced by myocardial infarction, Kawasaki disease, non-alcoholic steatohepatitis (NASH), organ transplant rejection, atherosclerosis, type I or type 2 diabetes, rheumatoid arthritis, osteoporosis, acute lung injury, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pain, Alzheimer's disease, lateral sclerosis. Petition 870250082980, dated 09 / 15 / 2025, p. 328 / 331 19 / 19 amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), stroke, Huntington's disease, frontotemporal dementia (FTD), multiple sclerosis (MS), isolated demyelinating diseases of the central nervous system, osteoarthritis, Crohn's disease, and ulcerative colitis.

40. Antibody or polypeptide, according to any one of claims 1 to 28, the polynucleotide, according to claim 29, the vector, according to claim 30 or 31, the host cell, according to claim 32, or the pharmaceutical composition, according to claim 33, characterized in that it is for use in a medicament.

41. Antibody or polypeptide, according to any one of claims 1 to 28, the polynucleotide, according to claim 29, the vector, according to claim 30 or 31, the host cell, according to claim 32, or the pharmaceutical composition, according to claim 33, characterized in that it is for use in the treatment of an inflammatory disorder or degenerative disease in a subject in need thereof.

42. Use, according to claim 41, characterized in that the inflammatory disorder or degenerative disease is selected from the group consisting of organ reperfusion injury, such as reperfusion injury induced by myocardial infarction, Kawasaki disease, non-alcoholic steatohepatitis (NASH), organ transplant rejection, atherosclerosis, type I or type 2 diabetes, rheumatoid arthritis, osteoporosis, acute lung injury, asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pain, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), stroke, Huntington's disease, frontotemporal dementia (FTD), multiple sclerosis (MS), isolated demyelinating diseases of the central nervous system, osteoarthritis, Crohn's disease and ulcerative colitis. Petition 870250082980, dated 09 / 15 / 2025, pages 329 / 331