Antibody-drug conjugates that bind CDCP1 and uses thereof

Abstract

The present disclosure provides compounds and antibody-drug conjugates and methods of use thereof, including methods for treating cancer.

Description

Docket No. 133186-5032-WOANTIBODY-DRUG CONJUGATES THAT BIND CDCP1 AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 721,161, filed November 15, 2024, which is incorporated by reference herein in its entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing that has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. The Sequence Listing for this application is labeled “133186-5032-WO_Sequence_Listing.xml”, which was created on October 31, 2025, and is 566,069 bytes in size.FIELD

[0003] The disclosure generally relates to antibody-drug conjugates and methods for treating cancer and other diseases, including CUB domain-containing protein 1 (CDCP1)-targeted therapies.BACKGROUND

[0004] While numerous chemotherapeutic agents have been developed, many often demonstrate unacceptable toxicity and or lack of specificity for cancer cells over non-cancerous tissues. To avoid the non-specific cytotoxic effects of chemotherapeutic agents, targeted antibody therapy has revolutionized cancer treatment with several monoclonal antibodies demonstrating clinical potential. Because antibodies against tumor-specific antigens often lack therapeutic activities, they have been conjugated to cytotoxic agents in order to combine the effectiveness of chemotherapy with the targeting of antibodies. In principle, selective delivery of cytotoxic agents to specific tumor tissues by antibody binding should reduce the systemic toxicity of traditional small-molecule chemotherapeutics.

[0005] Since a successful antibody-drug conjugate (ADC) approach must successfully bind to a target antigen in order to deliver a toxic payload to a target cell without significant binding to non-target cells, it is crucial that the ADC be able to deliver a toxic payload to a target cell, be internalized thereby, and then release the payload once inside the appropriate compartment within the cell.DBl / 163717029.3 1Docket No. 133186-5032-WO

[0006] CDCP1 is widely expressed in human epithelial tissues. CDCP1 functions in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis, but its phosphorylation is only observed in mitotically detached or shedding cells, consistent with its role in the negative regulation of cell adhesion. The phosphorylation of CDCP1 is seen in many cancers, including some pre-invasive cancers as well as in invasive tumors and in tumor metastases.

[0007] Despite a deepening understanding of tumor-specific proteins to target with ADC therapy, the need for specific CDCP1 -targeted ADCs that can be used for therapeutic purposes in the treatment of cancer remains unmet in the art.SUMMARY

[0008] In aspects, the disclosure provides an antibody-drug conjugate (ADC) of formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds to CUB Domain- Containing Protein-1 (CDCP1);U is a bond or a linker;D is a drug moiety comprising an auristatin; andn is an integer from 1 to 20.

[0009] In embodiments, the auristatin is selected from auristatin E or an analogue thereof, auristatin F or an analogue thereof, monomethyl auristatin E (MMAE) or an analogue thereof, monomethyl auristatin F (MMAF) or an analogue thereof, dolastatin 10 or an analogue thereof, monomethyl auristatin D (MMAD) or an analogue thereof, auristatin PE or an analogue thereof, auristatin PYE or an analogue thereof, PF-06380101 or an analogue thereof, symplostatin 1 or an analogue thereof, symplostatin 3 or an analogue thereof, dolastatin H or an analogue thereof, and isodolastatin H or an analogue thereof.

[0010] In embodiments, D is selected from any one of formula 1001-1157.

[0011] In embodiments, L is a bond or a linker comprising one or more groups selected from C₁-C₆ alkyl, C=O, -NH-, ethylene glycol, optionally 2-50 or 2-10 ethylene glycol units, valinecitrulline (val-cit), 6-maleimidocaproyl (me), 6-succinimidylcaproyl, 6-(2,5-dioxo-3λ3-pyrrolidin-1-yl)caproyl, methoxy-polyethylene glycol maleimide 6 (MalPeg6), p-DBl / 163717029.3 2Docket No. 133186-5032-WOaminobenzylcarbamate (PABC), dimethylaminoethanol (DMAE), 3-maleimidopropanoyl (MP), 3-succinimidylpropanoyl, 3-(2.5-dioxo-3 ’-pyrrolidin-l-yl)propanoyl. hydrolyzed Peg- maleimides, hydrolyzed maleimide, hydrolyzed succinimide, p-aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2- pyridylthio) pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl) cyclohexane- 1 carboxylate (SMCC), N-Succinimidyl (4-iodo-acetyl) aminobenzoate (SIAB), 6- maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-val-cit-PAB), and 6- maleimidocaproyl-valine-citrulline-p-aminobenzylcarbamate (mc-val-cit-PABC), an amino acid, optionally (D)-valine, (L)-valine, (D)-alanine, and / or (L)-alanine, an amino acid sequence, optionally valine -alanine (Vai-Ala), alanine-phenylalanine (Ala-Phe), alanine -alanine -alanine (Ala-Ala-Ala), or glycine-glycine-phenylalanine-glycine (Gly-Gly-Phe-Gly), and maleimide.

[0012] In embodiments, L is a bond or a linker comprising one or more groups selected from succinimide, an oxime, a bisulfone, a heterocycle, optionally a triazole or an isoxazolidine, an amide, and a thioether, an alkenyl phosphorous group, and an alkyl phosphorous group.

[0013] In embodiments, L is a bond or a linker selected from:DBl / 163717029.3 3Docket No. 133186-5032-WOwherein, XAAis an amino acid sequence having 1 to 5 amino acid moieties.

[0014] In embodiments, XAA is selected from alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), valine (Val), selenocysteine, homo-alanine (a-aminobutyric acid), norvaline, norleucine, Val-Ala, Tyr-Arg, Phe-Arg, Val-Gln, Val-Cit, Asn-Asn, Tyr-Met, Leu-Gin, Val-Arg, Met-Thr, Phe-Gln, Thr-Thr, Val-Thr, Ala-Ala, Val-Met, Leu-Met, Ala-Asn, D-Val-D-Gln, D-Ala-D-Ala, Phe-Met, alanine- alanine-alanine, valine-alanine-alanine, glutamic acid-valine-citrulline, valine-lysine-glycine, glycine-glycine-phenylalanine-glycine, glutamic acid-aspartic acid-phenylalanine-tryptophan, glycine-phenylalanine-leucine-glycine, and alanine-leucine-alanine-leucine.

[0015] In embodiments, L is a bond or a linker selected from:DBl / 163717029.3 4Docket No. 133186-5032-WODB1 / 163717029.3 5Docket No. 133186-5032-WO

[0016] In embodiments, n is an integer from 1 to 10. In embodiments, n is 4 or 8.

[0017] In embodiments, the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 2,(b) a CDRH2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 3, and(c) a CDRH3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 4,and (ii) a light chain variable region (VL) that comprises:(a) a CDRL1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 6,(b) a CDRL2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 7, and(c) a CDRL3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 8.DB1 / 163717029.3 6Docket No. 133186-5032-WO

[0018] In embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 1, and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 5.

[0019] In embodiments, the antibody or antigen binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 1 and / or a VL comprising the amino acid sequence of SEQ ID NO: 5.

[0020] In embodiments, the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 16,(b) a CDRH2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 17, and(c) a CDRH3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 18,and (ii) a light chain variable region (VL) that comprises:(a) a CDRL1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 20,(b) a CDRL2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 21, and(c) a CDRL3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 22.

[0021] In embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 15, and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at leastDBl / 163717029.3 7Docket No. 133186-5032-WOabout 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 19.

[0022] In embodiments, the antibody or antigen binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and / or a VL comprising the amino acid sequence of SEQ ID NO: 19.

[0023] In embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

[0024] In embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247- 249 and / or a VL that comprises an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

[0025] In embodiments, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a light chain comprising an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequenceDBl / 163717029.3 8Docket No. 133186-5032-WOselected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

[0026] In embodiments, the antibody or antigen binding fragment thereof comprises a heavy chain that comprises an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247- 249 and / or a light chain that comprises an amino acid sequence selected from SEQ ID NOs: 250- 467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

[0027] In embodiments, the antibody-drug conjugate has a drug-to-antibody ratio (DAR) ranging from about 1 to about 10, optionally wherein the DAR is about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10, optionally DAR is about 4, optionally DAR is about 8.

[0028] In aspects, the disclosure provides a pharmaceutical composition comprising the antibody-drug conjugate of formula (I); and a pharmaceutically acceptable carrier.

[0029] In aspects, the disclosure provides a method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the antibody-drug conjugate of formula (I), or the pharmaceutical composition of the disclosure.

[0030] In embodiments, the cancer is selected from pancreatic cancer, breast cancer, prostate cancer, lymphoma, skin cancer, colon cancer, melanoma, malignant melanoma, ovarian cancer, brain cancer, primary brain carcinoma, head-neck cancer, glioma, glioblastoma, liver cancer, bladder cancer, non-small cell lung cancer, head or neck carcinoma, breast carcinoma, ovarian carcinoma, lung carcinoma, small -cell lung carcinoma, Wilms’ tumor, cervical carcinoma, testicular carcinoma, bladder carcinoma, pancreatic carcinoma, stomach carcinoma, colon carcinoma, prostatic carcinoma, genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma, myeloma, multiple myeloma, adrenal carcinoma, renal cell carcinoma, endometrial carcinoma, adrenal cortex carcinoma, malignant pancreatic insulinoma, malignant carcinoid carcinoma, choriocarcinoma, mycosis fungoides, malignant hypercalcemia, cervical hyperplasia, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, chronic granulocytic leukemia, acute granulocytic leukemia, hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi’s sarcoma, polycythemia vera, essential thrombocytosis, Hodgkin’s disease, non-Hodgkin’s lymphoma, soft- tissue sarcoma, osteogenic sarcoma, primary macroglobulinemia, or retinoblastoma, and the like.DBl / 163717029.3 9Docket No. 133186-5032-WO

[0031] In embodiments, the cancer is acoustic neuroma, adenocarcinoma, angiosarcoma, astrocytoma, basal cell carcinoma, bile duct carcinoma, bladder carcinoma, brain cancer, breast cancer, triple -negative breast cancer (TNBC), bronchogenic carcinoma, cervical cancer, chordoma, choriocarcinoma, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, embryonal carcinoma, endotheliocarcinoma, ependymoma, epithelial carcinoma, esophageal cancer, Ewing’s tumor, fibrosarcoma, gastric cancer, glioblastoma multiforme, glioma, head and neck cancer, hemangioblastoma, hepatoma, kidney cancer, leiomyosarcoma, liposarcoma, lung cancer, lymphangioendotheliosarcoma, lymphangiosarcoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, myxosarcoma, nasal cancer, neuroblastoma, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinoma, papillary carcinoma, pinealoma, prostate cancer, rabdomyosarcoma, rectal cancer, renal cell carcinoma, retinoblastoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, squamous cell carcinoma, stomach cancer, sweat gland carcinoma, synovioma, testicular cancer, small cell lung carcinoma, throat cancer, uterine cancer, Wilms’ tumor, blood cancer, acute erythroleukemic leukemia, acute lymphoblastic B-cell leukemia, acute lymphoblastic T-cell leukemia, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, acute monoblastic leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocytic leukemia, acute promyelocytic leukemia, acute undifferentiated leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, hairy cell leukemia, myeloma, multiple myeloma, heavy chain disease, Hodgkin’s disease, non-Hodgkin’s lymphoma, polycythemia vera, and Waldenstrom’s macroglobulinemia. In embodiments, the cancer is selected from gastrointestinal cancer, colorectal cancer, breast cancer, prostate cancer, and pancreatic cancer

[0032] In embodiments, the cancer is triple-negative breast cancer (TNBC). In embodiments, the cancer is colorectal cancer. In embodiments, the cancer is pancreatic ductal adenocarcinoma (PDAC). In embodiments, the cancer is prostate adenocarcinoma (PAC). In embodiments, the cancer is colon adenocarcinoma (CAD). In embodiments, the cancer is non-small cell lung cancer (NSCLC). In embodiments, the cancer is breast invasive carcinoma. In embodiments, the cancer is lung squamous cell carcinoma (LSQCC). In embodiments, the cancer is bladder carcinoma. In embodiments, the cancer is bladder urothelial carcinoma.DBl / 163717029.3 10Docket No. 133186-5032-WOBRIEF DESCRIPTION OF THE DRAWINGS

[0033] The foregoing summary, as well as the following detailed description of embodiments of the disclosure, will be better understood when read in conjunction with the appended drawings and figures.

[0034] FIGs. 1A and IB respectively depict the exemplary antibody quality control via size exclusion chromatography (SEC, FIG. 1A) and hydrophobic chromatography (HIC, FIG. 1B).

[0035] FIGs. 2A, 2B, and 2C respectively depict the payload chemical structure (FIG. 2A), the post-conjugation aggregation by size exclusion chromatography (SEC, FIG. 2B) and the average calculated Drug-to-Antibody Ratio (DAR) from the exemplary ADC1 by hydrophobic interaction chromatography (HIC, FIG. 2C).

[0036] FIGs. 3A, 3B, and 3C respectively depict the payload chemical structure (FIG. 3A), the post-conjugation aggregation by size exclusion chromatography (SEC, FIG. 3B) and the calculated Drug-to-Antibody Ratio (DAR) from the exemplary ADC1 by hydrophobic interaction chromatography (HIC, FIG. 3C).

[0037] FIGs. 4A, 4B, and 4C respectively depict the payload chemical structure (FIG. 4A), the post-conjugation aggregation by size exclusion chromatography (SEC, FIG. 4B) and the calculated Drug-to-Antibody Ratio (DAR) from the exemplary ADC1 by hydrophobic interaction chromatography (HIC, FIG. 4C).

[0038] FIGs. 5A, 5B, 5C, 5D, 5E, 5F, and 5G collectively illustrate expression of the CDCP1 target in various cancer tissues from the Human Protein Atlas (proteinatlas.org). Prognostic value of CDCP1 in lung cancer, pancreatic cancer, and renal cancer (FIG.5A); CDCP1 RNA expression across various cancer types (FIG. 5B); CDCP1 protein expression across various cancer types (FIG. 5C, 5D), and; CDCP1 protein expression detected across various cancer types using polyclonal anti-CDCP1 antibody HPA010978 (FIG. 5E), polyclonal anti-CDCP1 antibody HPA010979 (FIG. 5F), and polyclonal anti-CDCP1 antibody CAB025637 (FIG. 5G).DETAILED DESCRIPTION

[0039] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this disclosure belongs. All patents and publications referred to herein are incorporated by reference in their entireties. DBl / 163717029.3 11Docket No. 133186-5032-WODefinitions

[0040] As used herein, the terms “administer,” “administration” or “administering” refer to (1) providing, giving, dosing, and / or prescribing by either a health practitioner or his authorized agent or under his or her direction according to the disclosure; and / or (2) putting into, taking or consuming by the mammal, according to the disclosure.

[0041] The terms “co-administration,” “co-administering,” “administered in combination with,” “administering in combination with,” “simultaneous,” and “concurrent,” as used herein, encompass administration of two or more active pharmaceutical ingredients to a subject so that both active pharmaceutical ingredients and / or their metabolites are present in the subject at the same time. Co-administration includes simultaneous administration in separate compositions, administration at different times in separate compositions, or administration in a composition in which two or more active pharmaceutical ingredients are present. Simultaneous administration in separate compositions and administration in a composition in which both agents are present are preferred.

[0042] The terms “active pharmaceutical ingredient” and “drug,” as used herein, refer to the antibody-drug conjugate of formula (I) of the disclosure, as well as other therapeutic agents described herein. “Active pharmaceutical ingredient” and “drug” may also include those compounds described herein that bind proteins, including but not limited to CDCP1, and thereby modulate protein activity.

[0043] The term “isostere” refers to a group or molecule whose chemical and / or physical properties are similar to those of another group or molecule. A “bioisostere” is a type of isostere and refers to a group or molecule whose biological properties are similar to those of another group or molecule. For example, a carboxylic acid may be replaced by one of the following bioisosteres for carboxylic acids, including, without limitation, alkyl esters (COOR), acylsulfonamides (CONR-SO2R), hydroxamic acids (CONR-OH), hydroxamates (CONR-OR), tetrazoles, hydroxyisoxazoles, isoxazol-3-ones, and sulfonamides (SO2NR), where each Rmay independently represent hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0044] The term “in vivo" refers to an event that takes place in a subject’s body.

[0045] The term in vitro refers to an event that takes places outside of a subject s body. In vitro assays encompass cell-based assays in which cells alive or dead are employed and may also encompass a cell-free assay in which no intact cells are employed.DBl / 163717029.3 12Docket No. 133186-5032-WO

[0046] The term “effective amount” or “therapeutically effective amount” refers to that amount of a compound or combination of compounds as described herein that is sufficient to effect the intended application including, but not limited to, disease treatment. A therapeutically effective amount may vary depending upon the intended application (in vitro or in vivo), or the subject and disease condition being treated (e.g., the weight, age and gender of the subject), the severity of the disease condition, the manner of administration, etc., which can readily be determined by one of ordinary skill in the art. The term also applies to a dose that will induce a particular response in target cells (e.g., the reduction of platelet adhesion and / or cell migration). The specific dose will vary depending on the particular compounds chosen, the dosing regimen to be followed, whether the compound is administered in combination with other compounds, timing of administration, the tissue to which it is administered, and the physical delivery system in which the compound is carried.

[0047] A “therapeutic effect” as that term is used herein, encompasses a therapeutic benefit and / or a prophylactic benefit. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0048] As used herein, the terms “treat,” “treatment,” and / or “treating” may refer to the management of a disease, disorder, or pathological condition, or symptom thereof with the intent to cure, ameliorate, stabilize, and / or control the disease, disorder, pathological condition or symptom thereof. Regarding control of the disease, disorder, or pathological condition more specifically, “control” may include the absence of condition progression, as assessed by the response to the methods recited herein, where such response may be complete (e.g., placing the disease in remission) or partial (e.g., lessening or ameliorating any symptoms associated with the condition). As used herein, the terms “prevent,” “preventing,” and / or “prevention” may refer to reducing the risk of developing a disease, disorder, or pathological condition.

[0049] As used herein, the terms “modulate” and “modulation” refer to a change in biological activity for a biological molecule (e.g., a targeted small molecule, untargeted moieties, such as, polysaccharides, a protein, gene, peptide, antibody or antigen binding fragment thereof, and the like), where such change may relate to an increase in biological activity (e.g., increased activity, agonism, activation, expression, upregulation, and / or increased expression) or decrease in biological activity (e.g., decreased activity, antagonism, suppression, deactivation, downregulation, and / or decreased expression) for the biological molecule.DBl / 163717029.3 13Docket No. 133186-5032-WO

[0050] The terms “QD,” “qd,” or “q.d.” mean quaque die, once a day, or once daily. The terms “BID,” “bid,” or “b.i.d.” mean bis in die, twice a day, or twice daily. The terms “TID,” “tid,” or “t.i.d.” mean ter in die, three times a day, or three times daily. The terms “QID,” “qid,” or “q.i.d.” mean quater in die, four times a day, or four times daily.

[0051] The term “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counter ions known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Preferred inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid. Preferred organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid and salicylic acid. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese and aluminum. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins. Specific examples include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In embodiments, the pharmaceutically acceptable base addition salt is chosen from ammonium, potassium, sodium, calcium, and magnesium salts. The term “cocrystal” refers to a molecular complex derived from a number of cocrystal formers known in the art. Unlike a salt, a cocrystal typically does not involve hydrogen transfer between the cocrystal and the drug, and instead involves intermolecular interactions, such as hydrogen bonding, aromatic ring stacking, or dispersive forces, between the cocrystal former and the drug in the crystal structure.

[0052] “Pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” or “physiologically compatible” carrier or carrier medium is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and inert ingredients. The use of such pharmaceutically acceptable carriers or pharmaceutically acceptable excipients for active pharmaceutical ingredients is well known in the art. Except insofar as any conventional pharmaceutically acceptable carrier or pharmaceutically acceptable excipient is incompatible with the active pharmaceutical ingredient, its use in the therapeutic compositions of the disclosure is contemplated. Additional activeDBl / 163717029.3 14Docket No. 133186-5032-WOpharmaceutical ingredients, such as other drugs, can also be incorporated into the described compositions and methods.

[0053] A “prodrug” refers to a derivative of a compound described herein, the pharmacologic action of which results from the conversion by chemical or metabolic processes in vivo to the active compound. Prodrugs include compounds wherein an amino acid residue, or a polypeptide chain of two or more (e.g., two, three or four) amino acid residues is covalently joined through an amide or ester bond to a free amino, hydroxyl or carboxylic acid group. The amino acid residues include but are not limited to the 20 naturally occurring amino acids commonly designated by one or three letter symbols but also include, for example, 4- hydroxyproline, hydroxylysine, desmosine, isodesmosine, 3- methylhistidine, beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine and methionine sulfone. Additional types of prodrugs are also encompassed. For instance, free carboxyl groups can be derivatized as amides or alkyl esters (e.g., methyl esters and acetoxy methyl esters). Prodrug esters as employed herein includes esters and carbonates formed by reacting one or more hydroxyls of compounds of the method of the disclosure with alkyl, alkoxy, or aryl substituted acylating agents employing procedures known to those skilled in the art to generate acetates, pivalates, methylcarbonates, benzoates and the like. As further examples, free hydroxyl groups may be derivatized using groups including but not limited to hemisuccinates, phosphate esters, dimethylaminoacetates, and phosphoryloxymethyloxycarbonyls, as outlined in Advanced Drug Delivery Reviews, 1996, 19, 115. Carbamate prodrugs of hydroxyl and amino groups are also included, as are carbonate prodrugs, sulfonate prodrugs, sulfonate esters and sulfate esters of hydroxyl groups. Free amines can also be derivatized to amides, sulfonamides or phosphonamides. All of the stated prodrug moieties may incorporate groups including but not limited to ether, amine and carboxylic acid functionalities. Moreover, any compound that can be converted in vivo to provide the bioactive agent is a prodrug within the scope of the disclosure. Various forms of prodrugs are well known in the art. A comprehensive description of pro drugs and prodrug derivatives are described in: (a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al., (Academic Press, 1996); (b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985); (c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson and H. Bundgaard, eds., (Harwood Academic Publishers, 1991). In general, prodrugs may be designed to improve the penetration of a drug across biological membranes in order to obtain improved drug absorption, to prolong duration of action of a drug (slow release of the parent drug from a prodrug, decreased first-pass metabolism of the drug), to target the drug action (e.g.,DBl / 163717029.3 15Docket No. 133186-5032-WOorgan or tumor-targeting, lymphocyte targeting), to modify or improve aqueous solubility of a drug (e.g., i.v. preparations and eyedrops), to improve topical drug delivery (e.g., dermal and ocular drug delivery), to improve the chemical / enzymatic stability of a drug, or to decrease off- target drug effects, and more generally in order to improve the therapeutic efficacy of the compounds utilized in the disclosure.

[0054] Unless otherwise stated, the chemical structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds where one or more hydrogen atoms is replaced by deuterium or tritium, or wherein one or more carbon atoms is replaced by13C- or14C-enriched carbons, are within the scope of this disclosure.

[0055] “Alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to ten carbon atoms (e.g., (Ci-io)alkyl or Ci-io alkyl). Whenever it appears herein, a numerical range such as “1 to 10” refers to each integer in the given range, e.g., “1 to 10 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms, although the definition is also intended to cover the occurrence of the term “alkyl” where no numerical range is specifically designated. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, w-butyl. isobutyl, scc-butyl isobutyl, tertiary butyl, pentyl, isopentyl, neopentyl, hexyl, septyl, octyl, nonyl and decyl. The alkyl moiety may be attached to the rest of the molecule by a single bond, such as for example, methyl (Me), ethyl (Et), w-propyl (Pr), 1 -methylethyl (isopropyl), w-butyl. w-pcntyl. 1,1 -dimethylethyl ( / -butyl) and 3 -methylhexyl. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted by one or more of substituents which are independently heteroalkyl, acylsulfonamido, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2(where t is 1 or 2), or -PO(ORa)2where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.DBl / 163717029.3 16Docket No. 133186-5032-WO

[0056] “Alkylaryl” refers to an -(alkyl)aryl radical where aryl and alkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for aryl and alkyl respectively.

[0057] “Alkylhetaryl” refers to an -(alkyl)hetaryl radical where hetaryl and alkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for aryl and alkyl respectively.

[0058] “Alkylheterocycloalkyl” refers to an -(alkyl) heterocyclic radical where alkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for heterocycloalkyl and alkyl respectively.

[0059] An “alkene” moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon double bond, and an “alkyne” moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon triple bond. The alkyl moiety, whether saturated or unsaturated, may be branched, straight chain, or cyclic.

[0060] “Alkenyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond, and having from two to ten carbon atoms (z.e., (C2-io)alkenyl or C2-10 alkenyl). Whenever it appears herein, a numerical range such as “2 to 10” refers to each integer in the given range - e.g., "2 to 10 carbon atoms” means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms. The alkenyl moiety may be attached to the rest of the molecule by a single bond, such as for example, ethenyl (z.e., vinyl), prop-l-enyl (z.e., allyl), but-l-enyl, pent-l-enyl and penta- 1,4-dienyl. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted by one or more substituents which are independently alkyl, heteroalkyl, acylsulfonamido, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, trimethylsilanyl, -ORa, -SRa, -S(O)tRa(where t is 1 or 2), -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -C(O)N(Ra)2, -OC(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)N(Ra)2, -N(Ra)C(O)Ra, -N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.DBl / 163717029.3 17Docket No. 133186-5032-WO

[0061] “Alkenyl-cycloalkyl” refers to an -(alkenyl)cycloalkyl radical where alkenyl and cycloalkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for alkenyl and cycloalkyl respectively.

[0062] “Alkynyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to ten carbon atoms (z.e., (C2-io)alkynyl or C2-10 alkynyl). Whenever it appears herein, a numerical range such as “2 to 10” refers to each integer in the given range - e.g., "2 to 10 carbon atoms” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms. The alkynyl may be attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl and hexynyl. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more substituents which are independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, acylsulfonamido, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2(where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0063] “Alkynyl-cycloalkyl” refers to an -(alkynyl)cycloalkyl radical where alkynyl and cycloalkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for alkynyl and cycloalkyl respectively.

[0064] “Acylsulfonamide” refers to the group -C(=O)NRa-S(=O)2Ra, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl.

[0065] “Carboxaldehyde” refers to a -(C=O)H radical.

[0066] “Carbonyl” refers to the group -C(=O)-. Carbonyl groups may be substituted with the following exemplary substituents: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, hydroxamate, heterocycloalkyl, acylsulfonamido, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -NRa-ORa-, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra,DBl / 163717029.3 18Docket No. 133186-5032-WO-N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, aryl, aralkyl, carbocyclylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0067] “Carboxyl” refers to a -(C=0)0H radical.

[0068] “Cyano” refers to a -CN radical.

[0069] “Cycloalkyl” refers to a monocyclic or polycyclic radical that contains only carbon and hydrogen, and may be saturated, or partially unsaturated. Cycloalkyl groups include groups having from 3 to 10 ring atoms (z.e., (C3-io)cycloalkyl or C3-10 cycloalkyl). Whenever it appears herein, a numerical range such as “3 to 10” refers to each integer in the given range - e.g., “3 to 10 carbon atoms” means that the cycloalkyl group may consist of 3 carbon atoms, etc., up to and including 10 carbon atoms. Illustrative examples of cycloalkyl groups include, but are not limited to the following moieties: cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, norbomyl, and the like. Unless stated otherwise specifically in the specification, a cycloalkyl group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, acylsulfonamido, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, trimethylsilanyl, -ORa, -N(Ra)2, -C(O)Ra, -OC(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -SRa, -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2(where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0070] “Cycloalkyl-alkenyl” refers to a -(cycloalkyl)alkenyl radical where cycloalkyl and alkenyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for cycloalkyl and alkenyl, respectively.

[0071] “Cycloalkyl-heterocycloalkyl” refers to a -(cycloalkyl)heterocycloalkyl radical where cycloalkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for cycloalkyl and heterocycloalkyl, respectively.DBl / 163717029.3 19Docket No. 133186-5032-WO

[0072] “Cycloalkyl-heteroaryl” refers to a -(cycloalkyl)heteroaryl radical where cycloalkyl and heteroaryl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for cycloalkyl and heteroaryl, respectively.

[0073] The term “alkoxy” refers to the group -O-alkyl, including from 1 to 8 carbon atoms of a straight, branched, cyclic configuration and combinations thereof attached to the parent structure through an oxygen. Examples include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy and cyclohexyloxy. “Lower alkoxy” refers to alkoxy groups containing one to six carbons.

[0074] The term “substituted alkoxy” refers to alkoxy wherein the alkyl constituent is substituted (z.e., -O-(substituted alkyl)). Unless stated otherwise specifically in the specification, the alkyl moiety of an alkoxy group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, acylsulfonamido, alkynyl, aryl, arylalkyl, hydroxy, cycloalkyl, heterocycloalkyl, hydroxamate, heteroaryl, heteroarylalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2(where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, aryl, aralkyl, carbocyclylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0075] The term “alkoxycarbonyl” refers to a group of the formula (alkoxy) (C=O)- attached through the carbonyl carbon wherein the alkoxy group has the indicated number of carbon atoms. Thus a (Ci-e)alkoxycarbonyl group is an alkoxy group having from 1 to 6 carbon atoms attached through its oxygen to a carbonyl linker. “Lower alkoxycarbonyl” refers to an alkoxycarbonyl group wherein the alkoxy group is a lower alkoxy group.

[0076] The term “substituted alkoxycarbonyl” refers to the group (substituted alkyl)-O-C(O)- wherein the group is attached to the parent structure through the carbonyl functionality. Unless stated otherwise specifically in the specification, the alkyl moiety of an alkoxycarbonyl group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, acylsulfonamido, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2,DBl / 163717029.3 20Docket No. 133186-5032-WO-N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0077] “Acyl” refers to the groups (alkyl)-C(O)-, (aryl)-C(O)-, (heteroaryl)-C(O)-, (heteroalkyl)-C(O)- and (heterocycloalkyl)-C(O)-, wherein the group is attached to the parent structure through the carbonyl functionality. If the R radical is heteroaryl or heterocycloalkyl, the hetero ring or chain atoms contribute to the total number of chain or ring atoms. Unless stated otherwise specifically in the specification, the alkyl, aryl or heteroaryl moiety of the acyl group is optionally substituted by one or more substituents which are independently alkyl, heteroalkyl, acylsulfonamido, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -C(O)Ra, -C(O)ORa, -0C(0)N(Ra)2, -C(0)N(Ra)2, -N(Ra)2, -N(Ra)C(0)0Ra, -N(Ra)C(0)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0078] “Acyloxy” refers to a R(C=O)O- radical wherein R is alkyl, aryl, heteroaryl, heteroalkyl or heterocycloalkyl, which are as described herein. If the R radical is heteroaryl or heterocycloalkyl, the hetero ring or chain atoms contribute to the total number of chain or ring atoms. Unless stated otherwise specifically in the specification, the R of an acyloxy group is optionally substituted by one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -C(O)Ra, -C(O)ORa, -0C(0)N(Ra)2, -C(0)N(Ra)2, -N(Ra)C(0)Ra, -N(Ra)2, -N(Ra)C(0)0Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0079] “Amino” or “amine” refers to a -N(Ra)2 radical group, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, DBl / 163717029.3 21Docket No. 133186-5032-WOheterocycloalkylalkyl, heteroaryl or heteroarylalkyl, unless stated otherwise specifically in the specification. When a -N(Ra)2 group has two Rasubstituents other than hydrogen, they can be combined with the nitrogen atom to form a 4-, 5-, 6- or 7-membered ring. For example, -N(Ra)2 is intended to include, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl. Unless stated otherwise specifically in the specification, an amino group is optionally substituted by one or more substituents which independently are: alkyl, acylsulfonamido, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(NRa)N(Ra)2, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0080] The term “substituted amino” also refers to N-oxides of the groups -NHRd, and NRdRdeach as described above. N-oxides can be prepared by treatment of the corresponding amino group with, for example, hydrogen peroxide or m-chloroperoxybenzoic acid.

[0081] “Amide” or “amido” refers to a chemical moiety with formula -C(O)NRaRbor -NRaC(O)Rb, where Raand Rbare selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon), each of which moiety may itself be optionally substituted. The Raand Rbof - C(O)N RaRbamide may optionally be taken together with the nitrogen to which they are attached to form a 4-, 5-, 6- or 7-membered ring. Unless stated otherwise specifically in the specification, an amido group is optionally substituted independently by one or more of the substituents as described herein for alkyl, amino, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl. An amide may be an amino acid or a peptide molecule attached to a compound disclosed herein, thereby forming a prodrug. The procedures and specific groups to make such amides are known to those of skill in the art and can readily be found in seminal sources such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rdEd., John Wiley & Sons, New York, N. Y., 1999, which is incorporated herein by reference in its entirety.

[0082] The term “amino acid” refers to naturally occurring (or “canonical”) a-amino acids and their stereoisomers, unnatural (or “non-canonical”) amino acids and their stereoisomers, and modified or synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally-occurring amino acids. “Stereoisomers” of amino DBl / 163717029.3 22Docket No. 133186-5032-WOacids refers to mirror image isomers of the amino acids, such as L-amino acids or D-amino acids. For example, a stereoisomer of a naturally-occurring amino acid refers to the mirror image isomer of the naturally-occurring amino acid, i.e., the D-amino acid.

[0083] Naturally-occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, y-carboxyglutamate, and O- phosphoserine. Naturally-occurring a-amino acids include, without limitation, amino acids selected from alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), and valine (Vai). Stereoisomers of naturally- occurring a-amino acids include, without limitation, D-alanine (D-Ala), D-arginine (D-Arg), D- asparagine (D-Asn), D-aspartic acid (D-Asp), D-cysteine (D-Cys), D-glutamine (D-Gln), D- glutamic acid (D-Glu), D-glycine (D-Gly), D-histidine (D-His), D-isoleucine (D-Ile), D-leucine (D-Leu), D-lysine (D-Lys), D-methionine (D-Met), D-phenylalanine (D-Phe), D-proline (D-Pro), D-serine (D-Ser), D-threonine (Thr), D-tryptophan (D-Trp), D-tyrosine (D-Tyr), and D-valine (D-Val). Amino acid moieties disclosed herein are L-amino acids unless otherwise designated as a D-amino acid (e.g. D-Ala is D-alanine).

[0084] Unnatural amino acids include, without limitation, amino acid analogs, amino acid mimetics, and synthetic amino acids in either the L- or D-configuration that function in a manner similar to the naturally-occurring amino acids. For example, “amino acid analogs” are unnatural amino acids that have the same basic chemical structure as naturally-occurring amino acids, i.e., an a-carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs may have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid.

[0085] Non-limiting examples of unnatural amino acids include 1 -aminocyclopentane- 1- carboxylic acid (Acp), 1 -aminocyclobutane- 1 -carboxylic acid (Acb), 1 -aminocyclopropane- 1- carboxylic acid (Acpc), citrulline (Cit), homocitrulline (HoCit), a-aminohexanedioic acid (Aad), 3-(4-pyridyl)alanine (4-Pal), 3-(3-pyridyl)alanine (3-Pal), propargylglycine (Pra), a- aminoisobutyric acid (Aib), a-aminobutyric acid (Abu), norvaline (Nva), a,[3-diaminopropionic acid (Dpr), a,y-diaminobutyric acid (Dbu), a-tert-butylglycine (Bug), 3, 5 -dinitrotyrosine (Tyr(3,5-di NO2)), norleucine (Nle), 3-(2-naphthyl)alanine (Nal-2), 3-(l-naphthyl)alanine (Nal- 1), cyclohexylalanine (Cha), di-n-propylglycine (Dpg), cyclopropylalanine (Cpa), homoleucine DBl / 163717029.3 23Docket No. 133186-5032-WO(Hie), homoserine (HoSer), homoarginine (Har), homocysteine (Hey), methionine sulfoxide (Met(O)), methionine methylsulfonium (Met (S-Me)), a-cyclohexylglycine (Chg), 3-benzo- thienylalanine (Bta), taurine (Tau), hydroxyproline (Hyp), O-benzyl-hydroxyproline (Hyp(Bzl)), homoproline (HoPro), P-homoproline ( HoPro), thiazolidine-4-carboxylic acid (Thz), nipecotic acid (Nip), isonipecotic acid (IsoNip), 3-carboxymethyl-l-phenyl-l,3,8-triazaspiro[4,5]decan-4- one (Cptd), tetrahydro-isoquinoline-3-carboxylic acid (3-Tic), 5H-thiazolo [3,2-a]pyridine-3- carboxylic acid (Btd), 3 -aminobenzoic acid (3-Abz), 3-(2-thienyl)alanine (2-Thi), 3-(3- thienyl)alanine (3-Thi), a-aminooctanedioc acid (Asu), diethylglycine (Deg), 4-amino-4- carboxy-l,l-dioxo-tetrahydrothiopyran (Acdt), 1 -amino- l-(4-hydroxycyclohexyl) carboxylic acid (Ahch), 1 -amino- l-(4-ketocyclohexyl)carboxylic acid (Akch), 4-amino-4- carboxytetrahydropyran (Actp), 3 -nitrotyrosine (Tyr(3-NO2)), 1 -amino- 1 -cyclohexane carboxylic acid (Ach), l-amino-l-(3-piperidinyl)carboxylic acid (3-Apc), l-amino-l-(4- piperidinyl)carboxylic acid (4-Apc), 2-amino-3-(4-piperidinyl) propionic acid (4-App), 2- aminoindane-2 -carboxylic acid (Aic), 2-amino-2 -naphthylacetic acid (Ana), (2S, 5R)-5- phenylpyrrolidine-2-carboxylic acid (Ppca), 4-thiazoylalanine (Tha), 2-aminooctanoic acid (Aoa), 2-aminoheptanoic acid (Aha), ornithine (Om), azetidine-2-carboxylic acid (Aca), a- amino-3-chloro-4,5-dihydro-5-isoazoleacetic acid (Acdi), thiazolidine-2-carboxylic acid (Thz(2- COOH)), allylglycine (Agl), 4-cyano-2 -aminobutyric acid (Cab), 2-pyridylalanine (2 -Pal), 2- quinoylalanine (2-Qal), cyclobutylalanine (Cba), a phenylalanine analog, derivatives of lysine, ornithine (Om) and a,y-diaminobutyric acid (Dbu), stereoisomers thereof, and combinations thereof (see, e.g., Liu et al., Anal. Biochem., 295:9-16 (2001)). As such, the unnatural a-amino acids are present either as unnatural L-a-amino acids, unnatural D-a-amino acids, or combinations thereof.

[0086] “Amino acid mimetics” are chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that function in a manner similar to a naturally-occurring amino acid. Suitable amino acid mimetics include, without limitation, P- amino acids and y-amino acids. In P-amino acids, the amino group is bonded to the P-carbon atom of the carboxyl group such that there are two carbon atoms between the amino and carboxyl groups. In y-amino acids, the amino group is bonded to the y-carbon atom of the carboxyl group such that there are three carbon atoms between the amino and carboxyl groups. Suitable R groups for P- or y-amino acids include, but are not limited to, side-chains present in naturally-occurring amino acids and unnatural amino acids.DBl / 163717029.3 24Docket No. 133186-5032-WO

[0087] “Aromatic” or “aryl” or “Ar” refers to an aromatic radical with six to ten ring atoms (e.g., Ce-Cio aromatic or Ce-Cio aryl) which has at least one ring having a conjugated pi electron system which is carbocyclic (e.g., phenyl, fluorenyl, and naphthyl). Bivalent radicals formed from substituted benzene derivatives and having the free valences at ring atoms are named as substituted phenylene radicals. Bivalent radicals derived from univalent polycyclic hydrocarbon radicals whose names end in “-yl” by removal of one hydrogen atom from the carbon atom with the free valence are named by adding “-idene” to the name of the corresponding univalent radical, e.g., a naphthyl group with two points of attachment is termed naphthylidene. Whenever it appears herein, a numerical range such as “6 to 10” refers to each integer in the given range; e.g., “6 to 10 ring atoms” means that the aryl group may consist of 6 ring atoms, 7 ring atoms, etc., up to and including 10 ring atoms. The term includes monocyclic or fused-ring polycyclic (i.e., rings which share adjacent pairs of ring atoms) groups. Unless stated otherwise specifically in the specification, an aryl moiety is optionally substituted by one or more substituents which are independently alkyl, heteroalkyl, aryl, arylalkyl, heteroaryl, acylsulfonamido, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, heteroarylalkyl, hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)Ra, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0088] “Aralkyl” or “arylalkyl” refers to an (aryl)alkyl-radical where aryl and alkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for aryl and alkyl respectively.

[0089] ‘Ester” refers to a chemical radical of formula -COOR, where R is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon). The procedures and specific groups to make esters are known to those of skill in the art and can readily be found in seminal sources such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rdEd., John Wiley & Sons, New York, N. Y., 1999, which is incorporated herein by reference in its entirety. Unless stated otherwise specifically in the specification, an ester group is optionally substituted by one or more substituents which independently are: alkyl, acylsulfonamido, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy,DBl / 163717029.3 25Docket No. 133186-5032-WOhalo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0090] “Fluoroalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, as defined above, for example, trifluoromethyl, difluoromethyl, 2,2,2- trifluoroethyl, 1 -fluoromethyl -2-fluoroethyl, and the like. The alkyl part of the fluoroalkyl radical may be optionally substituted as defined above for an alkyl group.

[0091] “Halo,” “halide,” or, alternatively, “halogen” is intended to mean fluoro, chloro, bromo or iodo. The terms “haloalkyl,” “haloalkenyl,” “haloalkynyl,” and “haloalkoxy” include alkyl, alkenyl, alkynyl and alkoxy structures that are substituted with one or more halo groups or with combinations thereof. For example, the terms “fluoroalkyl” and “fluoroalkoxy” include haloalkyl and haloalkoxy groups, respectively, in which the halo is fluorine.

[0092] “Heteroalkyl,” “heteroalkenyl,” and “heteroalkynyl” refer to optionally substituted alkyl, alkenyl and alkynyl radicals and which have one or more skeletal chain atoms selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus or combinations thereof. A numerical range may be given - e.g., C1-C4 heteroalkyl which refers to the chain length in total, which in this example is 4 atoms long. A heteroalkyl group may be substituted with one or more substituents which independently are: alkyl, heteroalkyl, alkenyl, alkynyl, acylsulfonamido, cycloalkyl, heterocycloalkyl, hydroxamate, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2 (where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0093] “Heteroalkylaryl” refers to an -(heteroalkyl)aryl radical where heteroalkyl and aryl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for heteroalkyl and aryl, respectively.DBl / 163717029.3 26Docket No. 133186-5032-WO

[0094] “Heteroalkylheteroaryl” refers to an -(heteroalkyl)heteroaryl radical where heteroalkyl and heteroaryl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for heteroalkyl and heteroaryl, respectively.

[0095] “Heteroalkylheterocycloalkyl” refers to an -(heteroalkyl)heterocycloalkyl radical where heteroalkyl and heterocycloalkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for heteroalkyl and heterocycloalkyl, respectively.

[0096] “Heteroalkylcycloalkyl” refers to an -(heteroalkyl)cycloalkyl radical where heteroalkyl and cycloalkyl are as disclosed herein and which are optionally substituted by one or more of the substituents described as suitable substituents for heteroalkyl and cycloalkyl, respectively.

[0097] “Heteroaryl” or “heteroaromatic” or “HetAr” refers to a 5- to 18-membered aromatic radical (e.g, C5-C13 heteroaryl) that includes one or more ring heteroatoms selected from nitrogen, oxygen and sulfur, and which may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system. Whenever it appears herein, a numerical range such as “5 to 18” refers to each integer in the given range - e.g., “5 to 18 ring atoms” means that the heteroaryl group may consist of 5 ring atoms, 6 ring atoms, etc., up to and including 18 ring atoms. Bivalent radicals derived from univalent heteroaryl radicals whose names end in “-yl” by removal of one hydrogen atom from the atom with the free valence are named by adding “-idene” to the name of the corresponding univalent radical - e.g., a pyridyl group with two points of attachment is a pyridylidene. A N-containing “heteroaromatic” or “heteroaryl” moiety refers to an aromatic group in which at least one of the skeletal atoms of the ring is a nitrogen atom. The polycyclic heteroaryl group may be fused or non-fused. The heteroatom(s) in the heteroaryl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quatemized. The heteroaryl may be attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[6][l,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzofurazanyl, benzothiazolyl, benzothienyl(benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[ l,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, DBl / 163717029.3 27Docket No. 133186-5032-WO5,6-dihydrobenzo [ h ]quinazol iny 1, 5,6-dihydrobenzo [ h ]cinnol inyl, 6,7-dihydro-5H- benzo[6,7]cyclohepta[l,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furazanyl, furanonyl, furo[3,2-c]pyridinyl, 5, 6, 7, 8, 9, 10-hexahydrocycloocta[<7]pyrimidinyl, 5,6,7,8,9,10- hexahydrocycloocta[<7]pyridazinyl, 5, 6, 7, 8, 9, 10-hexahydrocycloocta[<7]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, isoxazol-3-one, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1 -phenyl- IH-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5, 6,7,8- tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5 ]thieno[2,3- oQpyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, thiapyranyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3- c]pyridinyl, and thiophenyl (i.e. thienyl). Unless stated otherwise specifically in the specification, a heteroaryl moiety is optionally substituted by one or more substituents which are independently: alkyl, acylsulfonamido, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heterocycloalkyl, hydroxamate, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -ORa, -SRa, -OC(O)Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, -OC(O)N(Ra)2, -C(O)N(Ra)2, -N(Ra)C(O)ORa, -N(Ra)C(O)Ra, -N(Ra)C(O)N(Ra)2, N(Ra)C(NRa)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(O)tN(Ra)2(where t is 1 or 2), or -PO(ORa)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0098] Substituted heteroaryl also includes ring systems substituted with one or more oxide (-O-) substituents, such as, for example, pyridinyl N-oxides.

[0099] “Heteroarylalkyl” refers to a moiety having an aryl moiety, as described herein, connected to an alkylene moiety, as described herein, wherein the connection to the remainder of the molecule is through the alkylene group.

[0100] “Heterocycloalkyl” refers to a stable 3- to 18-membered non-aromatic ring radical that comprises two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Whenever it appears herein, a numerical range such as “3 to 18” DBl / 163717029.3 28Docket No. 133186-5032-WOrefers to each integer in the given range - e.g., “3 to 18 ring atoms” means that the heterocycloalkyl group may consist of 3 ring atoms, 4 ring atoms, etc., up to and including 18 ring atoms. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems. The heteroatoms in the heterocycloalkyl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quatemized. The heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl may be attached to the rest of the molecule through any atom of the ring(s). Examples of such heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo- thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, a heterocycloalkyl moiety is optionally substituted by one or more substituents which independently are: alkyl, acylsulfonamido, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, hydroxamate, heteroaryl, heteroarylalkyl, hydroxy, halo, cyano, nitro, oxo, thioxo, trimethylsilanyl, -0Ra, -SRa, -0C(0)Ra, -N(Ra)2, -C(0)Ra, -C(0)0Ra, -C(0)N(Ra)2, -0C(0)N(Ra)2, -N(Ra)C(0)0Ra, -N(Ra)C(0)Ra, -N(Ra)C(0)N(Ra)2, -N(Ra)S(O)tRa(where t is 1 or 2), -N(Ra)C(NRa)N(Ra)2, -S(O)tRa(where t is 1 or 2), -S(O)tORa(where t is 1 or 2), -S(0)tN(Ra)2 (where t is 1 or 2), or P0(0Ra)2, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0101] “Heterocycloalkyl” also includes bicyclic ring systems wherein one non-aromatic ring, usually with 3 to 7 ring atoms, contains at least 2 carbon atoms in addition to 1-3 heteroatoms independently selected from oxygen, sulfur, and nitrogen, as well as combinations comprising at least one of the foregoing heteroatoms; and the other ring, usually with 3 to 7 ring atoms, optionally contains 1-3 heteroatoms independently selected from oxygen, sulfur, and nitrogen and is not aromatic.

[0102] “Hydroxamate” refers to the -C(0)NRa0Ramoiety, where each Rais independently hydrogen, alkyl, fluoroalkyl, carbocyclyl, carbocyclylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl.

[0103] “Nitro” refers to the -NO2 radical.DBl / 163717029.3 29Docket No. 133186-5032-WO

[0104] ‘ ‘Oxa” refers to the -O- radical.

[0105] ‘ ‘Oxo” refers to the =0 radical.

[0106] ‘ ‘Isomers” are different compounds that have the same molecular formula.“Stereoisomers” are isomers that differ only in the way the atoms are arranged in space - z.e., having a different stereochemical configuration. “Enantiomers” are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1: 1 mixture of a pair of enantiomers is a “racemic” mixture. The term “(±)” is used to designate a racemic mixture where appropriate. “Diastereoisomers” are stereoisomers that have at least two asymmetric atoms, but which are not mirror-images of each other. The absolute stereochemistry is specified according to the Cahn- Ingold-Prelog R-S system. When a compound is a pure enantiomer the stereochemistry at each chiral carbon can be specified by either (R) or (S). Resolved compounds whose absolute configuration is unknown can be designated (+) or (-) depending on the direction (dextro- or levorotatory) which they rotate plane polarized light at the wavelength of the sodium D line. Certain of the compounds described herein contain one or more asymmetric centers and can thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined, in terms of absolute stereochemistry, as (R) or (S). The present chemical entities, pharmaceutical compositions and methods are meant to include all such possible isomers, including racemic mixtures, optically pure forms and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers.

[0107] ‘ ‘Enantiomeric purity” as used herein refers to the relative amounts, expressed as a percentage, of the presence of a specific enantiomer relative to the other enantiomer. For example, if a compound, which may potentially have an (R)- or an (. S')-isomcric configuration, is present as a racemic mixture, the enantiomeric purity is about 50% with respect to either the (R)- or (S)-isomer, If that compound has one isomeric form predominant over the other, for example, 80% (S)-isomer and 20% (R)-isomer, the enantiomeric purity of the compound with respect to the (S)-isomeric form is 80%. The enantiomeric purity of a compound can be determined in a number of ways known in the art, including but not limited to chromatography using a chiral support, polarimetric measurement of the rotation of polarized light, nuclear magnetic resonance spectroscopy using chiral shift reagents which include but are not limited to lanthanide containing chiral complexes or Pirkle’s reagents, or derivatization of a compounds using a chiral DBl / 163717029.3 30Docket No. 133186-5032-WOcompound such as Mosher’s acid followed by chromatography or nuclear magnetic resonance spectroscopy.

[0108] In embodiments, an enantiomerically enriched composition has a higher potency with respect to therapeutic utility per unit mass than does the racemic mixture of that composition. Enantiomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred enantiomers can be prepared by asymmetric syntheses. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions, Wiley Interscience, New York (1981); E. L. Eliel, Stereochemistry of Carbon Compounds, McGraw-Hill, New York (1962); and E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds, Wiley- Interscience, New York (1994).

[0109] The terms “enantiomerically enriched” and “non-racemic,” as used herein, refer to compositions in which the percent by weight of one enantiomer is greater than the amount of that one enantiomer in a control mixture of the racemic composition (e.g., greater than 1: 1 by weight). For example, an enantiomerically enriched preparation of the (S)-enantiomer, means a preparation of the compound having greater than 50% by weight of the (S)-enantiomer relative to the (R)-enantiomer. such as at least 75% by weight, or such as at least 80% by weight. In embodiments, the enrichment can be significantly greater than 80% by weight, providing a “substantially enantiomerically enriched” or a “substantially non-racemic” preparation, which refers to preparations of compositions which have at least 85% by weight of one enantiomer relative to other enantiomer, such as at least 90% by weight, or such as at least 95% by weight. The terms “enantiomerically pure” or “substantially enantiomerically pure” refers to a composition that comprises at least 98% of a single enantiomer and less than 2% of the opposite enantiomer.

[0110] “Moiety” refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or appended to a molecule.

[0111] ‘ ‘Tautomers” are structurally distinct isomers that interconvert by tautomerization. “Tautomerization” is a form of isomerization and includes prototropic or proton-shift tautomerization, which is considered a subset of acid-base chemistry. “Prototropic tautomerization” or “proton-shift tautomerization” involves the migration of a proton accompanied by changes in bond order, often the interchange of a single bond with an adjacent double bond. Where tautomerization is possible (e.g., in solution), a chemical equilibrium ofDBl / 163717029.3 31Docket No. 133186-5032-WOtautomers can be reached. An example of tautomerization is keto-enol tautomerization. A specific example of keto-enol tautomerization is the interconversion of pentane-2, 4-dione and 4- hydroxypent-3-en-2-one tautomers. Another example of tautomerization is phenol-keto tautomerization. A specific example of phenol-keto tautomerization is the interconversion of pyridin-4-ol and pyridin-4(1H)-one tautomers.

[0112] A “leaving group or atom” is any group or atom that will, under selected reaction conditions, cleave from the starting material, thus promoting reaction at a specified site.Examples of such groups, unless otherwise specified, include halogen atoms and mesyloxy, p- nitrobenzensulphonyloxy and tosyloxy groups.

[0113] “Protecting group” is intended to mean a group that selectively blocks one or more reactive sites in a multifunctional compound such that a chemical reaction can be carried out selectively on another unprotected reactive site and the group can then be readily removed or deprotected after the selective reaction is complete. A variety of protecting groups are disclosed, for example, in T. H. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd Edition, John Wiley & Sons, New York (1999).

[0114] ‘ ‘Solvate” refers to a compound in physical association with one or more molecules of a pharmaceutically acceptable solvent.

[0115] ‘ ‘Substituted” means that the referenced group may have attached one or more additional groups, radicals or moieties individually and independently selected from, for example, acyl, alkyl, alkylaryl, cycloalkyl, aralkyl, aryl, carbohydrate, carbonate, heteroaryl, heterocycloalkyl, hydroxamate, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, ester, thiocarbonyl, isocyanato, thiocyanate, isothiocyanate, nitro, oxo, perhaloalkyl, perfluoroalkyl, phosphate, silyl, sulfinyl, sulfonyl, sulfonamidyl, sulfoxyl, sulfonate, urea, and amino, including mono- and di-substituted amino groups, and protected derivatives thereof. The substituents themselves may be substituted, for example, a cycloalkyl substituent may itself have a halide substituent at one or more of its ring carbons. The term “optionally substituted” means optional substitution with the specified groups, radicals or moieties.

[0116] “Sulfanyl” refers to groups that include -S-(optionally substituted alkyl), -S- (optionally substituted aryl), -S-(optionally substituted heteroaryl) and -S-(optionally substituted heterocycloalkyl).DBl / 163717029.3 32Docket No. 133186-5032-WO

[0117] “Sulfinyl” refers to groups that include -S(O)-H, -S(O)-(optionally substituted alkyl), -S(O)-(optionally substituted amino), -S(O)-(optionally substituted aryl), -S(O)- (optionally substituted heteroaryl) and -S(O)-(optionally substituted heterocycloalkyl).

[0118] “Sulfonyl” refers to groups that include -S(C>2)-H, -S(O2)-(optionally substituted alkyl), -S(O2)-(optionally substituted amino), -S(O2)-(optionally substituted aryl), -S(C>2)- (optionally substituted heteroaryl), and -S(O2)-(optionally substituted heterocycloalkyl).

[0119] “Sulfonamidyl” or “sulfonamide” refers to a -S(=O)2-NRR radical, where each R is selected independently from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon). The R groups in -NRR of the -S(=O)2-NRR radical may be taken together with the nitrogen to which it is attached to form a 4-, 5-, 6- or 7-membered ring. A sulfonamide group is optionally substituted by one or more of the substituents described for alkyl, cycloalkyl, aryl, heteroaryl, respectively.

[0120] “Sulfoxyl” refers to a -S(=O)2OH radical.

[0121] ‘ ‘Sulfonate” refers to a -S(=O)2-OR radical, where R is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) and heteroalicyclic (bonded through a ring carbon). A sulfonate group is optionally substituted on R by one or more of the substituents described for alkyl, cycloalkyl, aryl, heteroaryl, respectively.

[0122] Compounds of the disclosure also include crystalline and amorphous forms of those compounds, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof. “Crystalline form” and “polymorph” are intended to include all crystalline and amorphous forms of the compound, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms, as well as mixtures thereof, unless a particular crystalline or amorphous form is referred to.

[0123] The term “antibody” herein is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, dimers, multimers, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity. Antibodies may be murine, human, humanized, chimeric, or derived from other species. An antibody is a protein generated by the immune system that is capable of recognizing and binding to a specific antigen. (Janeway, C., DBl / 163717029.3 33Docket No. 133186-5032-WOTravers, P., Walport, M., Shlomchik (2001) Immuno Biology, 5th Ed., Garland Publishing, New York). A target antigen generally has numerous binding sites, also called epitopes, recognized by CDRs on multiple antibodies. Each antibody that specifically binds to a different epitope has a different structure. Thus, one antigen may have more than one corresponding antibody. An antibody includes a full-length immunoglobulin molecule or an immunologically active portion of a full-length immunoglobulin molecule, i.e., a molecule that contains an antigen-binding site that immunospecifically binds an antigen of a target of interest or part thereof, such targets including but not limited to, cancer cell or cells that produce autoimmune antibodies associated with an autoimmune disease.

[0124] An exemplary antibody such as an IgG comprises two heavy chains and two light chains. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. Each light chain is comprised of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[0125] The hypervariable region generally encompasses amino acid residues from about amino acid residues 24-34 (LCDR1; “L” denotes light chain), 50-56 (LCDR2) and 89-97 (LCDR3) in the light chain variable region and around about 31-35 (HCDR1; “H” denotes heavy chain), 50-65 (HCDR2), and 95-102 (HCDR3) in the heavy chain variable region; Kabat et al., SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991) and / or those residues forming a hypervariable loop (e.g. residues 26-32 (LCDR1), 50-52 (LCDR2) and 91-96 (LCDR3) in the light chain variable region and 26-32 (HCDR1), 53-55 (HCDR2) and 96-101 (HCDR3) in the heavy chain variable region; Chothia and Lesk (1987) J. Mol. Biol. 196:901-917.

[0126] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, e.g., the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibodyDBl / 163717029.3 34Docket No. 133186-5032-WOpreparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage-display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein.

[0127] The terms “nanobody,” “single -domain antibody (sdAb)”, “variable domain of a heavy chain-only antibody (VHH),” or “single domain-based VHH,” as used herein are used interchangeably and refer to single-domain heavy chain-only antibody derived from the Camelidae family. In embodiments, a nanobody is an antibody fragment derived from the Camelidae heavy-chain only IgG antibody.

[0128] The term “diabodies” refers to small antibody fragments with two antigen-binding sites, which fragments comprise a variable heavy domain (VH) connected to a variable light domain (VL) in the same polypeptide chain (VH-VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites.

[0129] The term “chimeric” antibody refers to a recombinant antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0130] A “human antibody” is an antibody that possesses an amino-acid sequence corresponding to that of an antibody produced by a human and / or has been made using any of the techniques for making human antibodies known to one of skill in the art. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigenbinding residues. Human antibodies can be produced using various techniques known in the art, including methods described in Cole et al, Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boemer et al, J. Immunol, 147(1): 86-95 (1991). See also van Dijk and van de Winkel, Curr. Opin. Pharmacol, 5: 368-74 (2001). Human antibodies can be prepared by administering the antigen to a transgenic animal that has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled, e.g., immunized HuMab mice (see, e.g., Nils Lonberg et al., 1994, Nature 368:856-859, WODBl / 163717029.3 35Docket No. 133186-5032-WO98 / 24884, WO 94 / 25585, WO 93 / 1227, WO 92 / 22645, WO 92 / 03918 and WO 01 / 09187 regarding HuMab mice), xenomice (see, e.g., U. S. Pat. Nos. 6,075,181 and 6,150,584 regarding XENOMOUSE™ technology) or Trianni mice (see, e.g., WO 2013 / 063391, WO 2017 / 035252 and WO 2017 / 136734).

[0131] The term “humanized antibody” refers to an antibody that has been engineered to comprise one or more human framework regions in the variable region together with non-human (e.g., mouse, rat, or hamster) complementarity-determining regions (CDRs) of the heavy and / or light chain. In certain embodiments, a humanized antibody comprises sequences that are entirely human except for the CDR regions. Humanized antibodies are typically less immunogenic to humans, relative to non-humanized antibodies, and thus offer therapeutic benefits in certain situations. Those skilled in the art will be aware of humanized antibodies and will also be aware of suitable techniques fortheir generation. See for example, Hwang, W. Y. K., et al., Methods 36:35, 2005; Queen et al., Proc. Natl. Acad. Sci. USA, 86: 10029-10033, 1989; Jones et al., Nature, 321:522-25, 1986; Riechmann et al., Nature, 332:323-27, 1988; Verhoeyen et al., Science, 239:1534-36, 1988; Orlandi et al., Proc. Natl. Acad. Sci. USA, 86:3833-37, 1989; U. S. Pat. Nos. 5,225,539; 5,530,101; 5,585,089; 5,693,761; 5,693,762; 6,180,370; and Selick et al., WO 90 / 07861, each of which is incorporated herein by reference in its entirety.

[0132] The “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, 5, a, y, and p, respectively. The immunoglobulin disclosed herein can be of any type (e.g., IgG, IgE, IgM, IgD, and IgA), class (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2) or subclass of immunoglobulin molecule. The immunoglobulins can be derived from any species. In one aspect, however, the immunoglobulin is of human, murine, or rabbit origin.

[0133] A “binding fragment thereof” refers to a fragment of an antibody that retains the ability to specifically bind to an antigen (preferably with substantially the same binding affinity). Such fragment is sometimes referred to as “antigen-binding domain” of an antibody (or simply “binding domain” ). Examples of an binding fragment thereof includes (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CHI domains; (iv) a Fv fragment consisting of the DBl / 163717029.3 36Docket No. 133186-5032-WOVL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., 1989 Nature 341:544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR), disulfide-linked Fvs (dsFv), diabodies; linear antibodies; single-chain antibody molecules (e.g., ScFv); nanobodies; anti-idiotypic (anti-Id) antibodies and intrabodies. Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they may be joined, using recombinant methods (e.g., by a synthetic linker) thus enabling them to be produced as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (ScFv)); see e.g., Bird et al., Science 242:423- 426 (1988) and Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883. Other forms of single chain antibodies, such as diabodies are also encompassed. Diabodies are bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen-binding sites (see e.g., Holliger et al., 1993, Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak eta / ., 1994, Structure 2:1121-1123).

[0134] An antibody “variable domain” refers to the variable region of the antibody light chain (VL) or the variable region of the antibody heavy chain (VH), either alone or in combination. As known in the art, the variable regions of the heavy and light chains each consist of four framework regions (FR) connected by three complementarity determining regions (CDRs), and contribute to the formation of the antigen-binding site of antibodies.

[0135] “Complementarity determining region” or “CDR” as the terms are used herein refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. There are three CDRs (termed CDR1, CDR2, and CDR3) within each VL and each VH.

[0136] As will be appreciated by those in the art, the exact numbering and placement of the CDRs can be different among different numbering systems. However, it should be understood that the disclosure of a variable heavy and / or variable light sequence includes the disclosure of the associated CDRs. Accordingly, the disclosure of each variable heavy region is a disclosure of the vhCDRs (e.g., vhCDRl, vhCDR2 and vhCDR3) and the disclosure of each variable light region is a disclosure of the vlCDRs (e.g., vlCDRl, vlCDR2 and vlCDR3).

[0137] In certain embodiments, the CDRs of an antibody can be determined according to the IMGT numbering system as described in Lefranc M-P, (1999) The Immunologist 7: 132- 136DBl / 163717029.3 37Docket No. 133186-5032-WOand Lefranc M-P et al, (1999) Nucleic Acids Res 27: 209-212. Unless stated otherwise herein, references to residue numbers in the variable domain of antibodies means residue numbering by the IMGT numbering system.

[0138] In other embodiments, the CDRs of an antibody can be determined according to MacCallum RM et al, (1996) J Mol Biol 262: 732-745. See also, e.g., Martin A. “Protein Sequence and Structure Analysis of Antibody Variable Domains,” in Antibody Engineering, Kontermann and Diibel, eds., Chapter 31, pp. 422-439, Springer-Verlag, Berlin (2001). In other embodiments, the CDRs of an antibody can be determined according to the AbM numbering scheme, which refers to AbM hypervariable regions, which represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM antibody modeling software (Oxford Molecular Group, Inc.). Residues in a variable domain are numbered according Kabat, which is a numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies. See, Kabat et al., 1991, Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or CDR of the variable domain. For example, a heavy chain variable domain may include a single amino acid insert (residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g., residues 82a, 82b, and 82c, according to Kabat) after heavy chain FR residue 82. The Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence. Various algorithms for assigning Kabat numbering are available. The algorithm implemented in the version 2.3.3 release of Abysis (www.abysis.org) is used herein to assign Kabat numbering to variable regions CDRL1, CDRL2, CDRL3, CDRH1, CDRH2, and CDRH3.

[0139] ‘ ‘Framework” or “framework region” or “FR” refers to variable domain residues other than hypervariable region (HVR) residues. The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4.

[0140] A “human consensus framework” is a framework which represents the most commonly occurring amino acid residues in a selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is a subgroup as in Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda Md. (1991), Vols. 1-3. In one embodiment, for the VL, the DBl / 163717029.3 38Docket No. 133186-5032-WOsubgroup is subgroup kappa I as in Kabat et al., supra. In one embodiment, for the VH, the subgroup is subgroup Ill as in Kabat et al., supra.

[0141] The “hinge region” is generally defined as stretching from 216-238 (EU numbering) or 226-251 (Kabat numbering) of human IgGl. The hinge can be further divided into three distinct regions, the upper, middle (e.g., core), and lower hinge.

[0142] The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991).

[0143] A “blocking” antibody or an “antagonist” antibody is one which inhibits or reduces biological activity of the antigen it binds. Certain blocking antibodies or antagonist antibodies substantially or completely inhibit the biological activity of the antigen.

[0144] An “epitope” is a term of art that indicates the site or sites of interaction between an antibody and its antigen(s). As described by (Janeway, C, Jr., P. Travers, et al. (2001).Immunobiology: the immune system in health and disease. Part II, Section 3- 8. New York, Garland Publishing, Inc.): “An antibody generally recognizes only a small region on the surface of a large molecule such as a protein... [Certain epitopes] are likely to be composed of amino acids from different parts of the [antigen] polypeptide chain that have been brought together by protein folding. Antigenic determinants of this kind are known as conformational or discontinuous epitopes because the structure recognized is composed of segments of the protein that are discontinuous in the amino acid sequence of the antigen but are brought together in the three-dimensional structure. In contrast, an epitope composed of a single segment of polypeptide chain is termed a continuous or linear epitope” (Janeway, C. Jr., P. Travers, et al. (2001).Immunobiology: the immune system in health and disease. Part II, Section 3-8. New York, Garland Publishing, Inc.).

[0145] The epitope / paratope residue can be defined by a specific criterion, e.g., distance between atoms in the Ab and the Ag (e.g., a distance of equal to or less than about 4 A from aDBl / 163717029.3 39Docket No. 133186-5032-WOheavy atom of the cognate antibody and a heavy atom of the antigen). In another aspect, an epitope / paratope residue can be characterized as participating in a hydrogen bond interaction with the cognate antibody / antigen, or with a water molecule that is also hydrogen bonded to the cognate antibody / antigen (water-mediated hydrogen bonding). In another aspect, an epitope / paratope residue can be characterized as forming a salt bridge with a residue of the cognate antibody / antigen. In yet another aspect, an epitope / paratope residue can be characterized as a residue having a non-zero change in buried surface area (BSA) due to interaction with the cognate antibody / antigen. At a less detailed level, epitope / paratope can be characterized through function, e.g., by competition binding with other Abs. The epitope / paratope can also be defined more generically as comprising amino acid residues for which substitution by another amino acid will alter the characteristics of the interaction between the Ab and Ag (e.g., alanine scanning).

[0146] An “antibody that binds to the same epitope” as a reference antibody refers to an antibody that contacts an overlapping set of amino acid residues of the antigen as compared to the reference antibody or blocks binding of the reference antibody to its antigen in a competition assay by 50% or more. The amino acid residues of an antibody that contact an antigen can be determined, for example, by determining the crystal structure of the antibody in complex with the antigen or by performing hydrogen / deuterium exchange. In embodiments, residues of an antibody that are within 5 A the antigen are considered to contact the antigen. In embodiments, an antibody that binds to the same epitope as a reference antibody blocks binding of the reference antibody to its antigen in a competition assay by 50% or more, and conversely, the reference antibody blocks binding of the antibody to its antigen in a competition assay by 50% or more.

[0147] ‘ ‘Fv” consists of a dimer of one heavy- and one light-chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the H and L chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody.

[0148] “Single-chain Fv” also abbreviated as “sFv” or “ScFv” are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain.Preferably, the sFv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Plückthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).DBl / 163717029.3 40Docket No. 133186-5032-WO

[0149] The term an “isolated antibody” when used to describe the various antibodies disclosed herein, means an antibody that has been identified and separated and / or recovered from a cell or cell culture from which it was expressed. Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and can include enzymes, hormones, and other proteinaceous or non- proteinaceous solutes. In embodiments, an antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC) approaches. For a review of methods for assessment of antibody purity, see, for example, Flatman et al., J. Chromatogr. B 848:79-87 (2007). In an embodiment, the antibody will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain.

[0150] An antibody that “preferentially binds” or “specifically binds” (used interchangeably herein) to an epitope is a term well understood in the art, and methods to determine such specific or preferential binding are also well known in the art. A molecule is said to exhibit “specific binding” or “preferential binding” if it reacts or associates more frequently, more rapidly, with greater duration and / or with greater affinity with a particular cell or substance than it does with alternative cells or substances. An antibody “specifically binds” or “preferentially binds” to a target if it binds with greater affinity, avidity, more readily, and / or with greater duration than it binds to other substances. In a non-limiting example, an antibody that specifically or preferentially binds to an epitope is an antibody that binds this epitope with greater affinity, avidity, more readily, and / or with greater duration than it binds to other epitopes or non-epitopes. It is also understood by reading this definition that, for example, an antibody (or moiety, or epitope) which specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. As such, “specific binding” or “preferential binding” does not necessarily require (although it can include) exclusive binding. Generally, but not necessarily, reference to binding means preferential binding.

[0151] The term “specific binding” or “specifically binds to” or is “specific for” a particular polypeptide or an epitope on a particular polypeptide target as used herein can be exhibited, for example, by a molecule having a Kd for the target of 10-4M or lower, alternatively 10-5M or lower, alternatively 10-6M or lower, alternatively 10-7M or lower, alternatively 10-8M or lower, alternatively 10-9M or lower, alternatively 10'10M or lower, alternatively 10-11M orDBl / 163717029.3 41Docket No. 133186-5032-WOlower, alternatively IO-12M or lower or a Kd in the range of IO-4M to IO-6M or IO-6M to IO-10M or IO-7M to IO-9M. As will be appreciated by the skilled artisan, affinity and KD values are inversely related. A high affinity for an antigen is measured by a low KD value. In one embodiment, the term “specific binding” refers to binding where a molecule binds to a particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or polypeptide epitope. As used herein the terms “specific binding,” “specifically binds,” and “selectively binds,” refer to antibody binding to an epitope.

[0152] A variety of assays may be used to select an antibody or peptide that specifically binds a molecule of interest. For example, solid-phase ELISA immunoassay, immunoprecipitation, BIAcore™ (GE Healthcare, Piscataway, NJ), fluorescence-activated cell sorting (FACS), Octet™ (ForteBio, Inc., Menlo Park, CA) and Western blot analysis are among many assays that may be used to identify an antibody that specifically reacts with an antigen or a receptor, or ligand binding portion thereof, that specifically binds with a cognate ligand or binding partner. Typically, a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 times background, even more specifically, an antibody is said to “specifically bind” an antigen when the equilibrium dissociation constant (KD) value is less or equal to 1 pM, such as less or equal to 100 nM, less or equal to 10 nM, less or equal to 100 pM, less or equal to 10 pM, or less or equal to 1 pM.

[0153] The term “affinity,” as used herein, means the strength of the binding of an antibody to an epitope. The affinity of an antibody is given by the dissociation constant Kd, defined as [Ab]x[Ag] / [Ab-Ag], where [Ab-Ag] is the molar concentration of the antibody-antigen complex, [Ab] is the molar concentration of the unbound antibody and [Ag] is the molar concentration of the unbound antigen. The affinity constant Ka is defined by 1 / Kd. Methods for determining the affinity of mAbs can be found in Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y., 1988), Coligan et al., eds., Current Protocols in Immunology, Greene Publishing Assoc, and Wiley Interscience, N. Y., (1992, 1993), and Muller, Meth. Enzymol. 92:589-601 (1983), which references are entirely incorporated herein by reference. One standard method well known in the art for determining the affinity of mAbs is the use of surface plasmon resonance (SPR) screening (such as by analysis with a BIAcore™ SPR analytical device).

[0154] The term “compete”, as used herein with regard to an antibody, means that binding of a first antibody, or an antigen-binding portion thereof, to an antigen reduces the subsequent binding of the same antigen by a second antibody or an antigen-binding portion thereof. In DBl / 163717029.3 42Docket No. 133186-5032-WOgeneral, the binding a first antibody creates steric hindrance, conformational change, or binding to a common epitope (or portion thereof), such that the binding of the second antibody to the same antigen is reduced. Standard competition assays may be used to determine whether two antibodies compete with each other. One suitable assay for antibody competition involves the use of the Biacore technology, which can measure the extent of interactions using surface plasmon resonance (SPR) technology, typically using a biosensor system (such as a BIACORE® system). For example, SPR can be used in an in vitro competitive binding inhibition assay to determine the ability of one antibody to inhibit the binding of a second antibody. Another assay for measuring antibody competition uses an ELISA-based approach.

[0155] The term “KD”, as used herein, is intended to refer to the dissociation constant of a particular antibody-antigen interaction. It is calculated by the formula: Koff / Kon = KD.

[0156] The term “ICso”, as used herein, is intended to refer to the effective concentration of antibody of the present disclosure needed to neutralize 50% of the bioactivity of IL-23 on human lymphoma DB cells in the bioassay described in Example 5: Inhibition of STAT3 activation in human DB cell Assay.

[0157] ‘ECso” with respect to an agent and a particular activity (e.g., binding to a cell, inhibition of enzymatic activity, activation or inhibition of an immune cell), refers to the efficient concentration of the agent which produces 50% of its maximum response or effect with respect to such activity. “EC100” with respect to an agent and a particular activity refers to the efficient concentration of the agent which produces its substantially maximum response with respect to such activity.Antibodv-Drug Conjugates

[0158] In aspects, the disclosure provides antibody-drug conjugates (ADCs). In some embodiments, the ADCs described herein comprise an antibody or antigen binding fragment thereof and a payload (z.e., a drug moiety). In some embodiments, the ADCs of the disclosure comprise an antibody or antigen binding fragment thereof, a linker, and a payload (z. e., a drug moiety). In some embodiments, the ADCs of the disclosure comprise an auristatin as the drug moiety. In embodiments, the ADCs of the disclosure comprise a linker conjugated to a drug moiety.

[0159] In aspects, the disclosure provides an antibody-drug conjugate (ADC) of formula (I):Ab-[L–D]nformula (I)DBl / 163717029.3 43Docket No. 133186-5032-WOwherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds to CUB Domain- Containing Protein-1 (CDCP1);L is a bond or a linker;D is a drug moiety comprising an auristatin; andn is an integer from 1 to 20.Drug Moieties

[0160] In one aspect, the disclosure provides drug moieties useful within the antibody-drug conjugates (ADCs) of formula (I).

[0161] In some embodiments, the antibody-drug conjugate (ADC) of formula (I) contains a drug moiety comprising an auristatin. Exemplary auristatins include, but are not limited to, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), auristatin F, auristatin F phenylenediamine (AFP), auristatin F hydroxylpropylamide (AF FTP A), monomethyl auristatin F hydroxylpropylamide (MMAF HP A), and dolastatin. Non-limiting examples of suitable auristatins are also described in U. S. Publication Nos. 2003 / 0083263, 2011 / 0020343, and 2011 / 0070248; PCT Application Publication Nos. WO 09 / 117531, WO 2005 / 081711, WO 04 / 010957, WO 02 / 088172, and WO 01 / 24763, and U. S. Patent Nos. 7498298, 6884869, 6323315, 6239104, 6124431, 6034065, 5780588, 5767237, 5665860, 5663149, 5635483, 5599902, 5554725, 5530097, 5521284, 5504191, 5410024, 5138036, 5076973, 4986988, 4978744, 4879278, 4816444, and 4486414, the disclosures of each of which are incorporated herein by reference in their entirety.

[0162] In some embodiments, the auristatin is selected from auristatin E or an analogue thereof, auristatin F or an analogue thereof, monomethyl auristatin E (MMAE) or an analogue thereof, monomethyl auristatin F (MMAF) or an analogue thereof, dolastatin 10 or an analogue thereof, monomethyl auristatin D (MMAD) or an analogue thereof, auristatin PE or an analogue thereof, auristatin PYE or an analogue thereof, PF-06380101 or an analogue thereof, symplostatin 1 or an analogue thereof, symplostatin 3 or an analogue thereof, dolastatin H or an analogue thereof, and isodolastatin H or an analogue thereof.

[0163] In some embodiments, the drug moiety (z.e., D) of the antibody-drug conjugate (ADC) of formula (I) is selected from any one of formula 1001-1157:DBl / 163717029.3 44Docket No. 133186-5032-WO Formula No. Structure7 Z1001 / H? 1A^7! »\N^><'CI'NV 'I'N H' / 'A1 0 1 0^ 0 0^ 0 XIZ rzYo X°1002 / z— / / ^o" / \_^ \Z_,z'o=\)oX°=0nY.SV \ / \ / Q Q— — 10 3 / / \ X ^A X z ♦ X _ ON— 9,. -hL 9n; zN<— — X, A1 0 ° / / = n n( / °= 1 O\ O O\ 0 i A °xIZ IZ ' '=i oY \ ) \ ^oo=1004 H ||z / — \ ) I H 1 / nn <Nxr n n1 O 1 O o iN H x1005Y. S Y1o,. 9NY TNn Y1 O 1 O\ O O\ 0 * i / 1006H || * ] IH? \1007 ^XNXX TNYX '91 O 1 °\ O O^ O XAs1008DB1 / 163717029.3 45Docket No. 133186-5032-WOFormula No. Structure / Y H1? Y O i H009 n Y r0i f r °\Y O Y O\Y O iNYJ1010 ^ zYVhlY O° / / A fr < AY iio YhoA i "u1011 - Y ° Y AA X °Y\ ° YY o Y AY YAy1012 / hs *Y^ o ihu rrNH20AA °\0°\ ° AAAYJ1013 / Y^h2 Y? ih20 0 0AYAYJ1014010150^A °\0°\0 1vA / 0DB1 / 163717029.3 46Docket No. 133186-5032-WOFormula No. Structure1 YY H 1016 YY H 9 I H J 9 IP ■\ 1\ 0N^N 1V 0^Y ONV 0^ r 0Nr AoA^ IZ rY° 0 ^ i / Q* o / ^1017 / YYhN YY IhYr N YY \--HZN y YNn Yf n X ° Y1 o 1 °\ o ° Y\°0 0\ / Y —YYH? Yr YY I H 9\ A zNKx _N— Q x Ax1018 N^Y Y if YN X / |1 O Y\ YY 1 °\ 0 X 0 AYu^ZI Y°7 YYH? Yr YY I H || 1019 ANYXNYVNT TNAN^^OH1 O Y\ 1 0^ 0 0^ 0 / YYh? Yr YY ih?A X ^N^ X ^N— Q X / 1020ZN Y |f IXf1 0 Y\ 1 °\ 0 O\ O AYLu1021 / \y H 9 Yr YY jhf x1022 A X / N^ X X ^\ ^N— <. N. XXZN Y;Nji n Ar if;N1 O 1 O\ 0 O\ 0 X^5xuDB1 / 163717029.3 47Docket No. 133186-5032-WO Formula No. Structure71023ZA Y X^hA X? _ fNY— k A I.hN. X? / N Y; N Y Y YYYf;01 O X^ 1 O\ 0 O\ 0u1024 7 Y H n O! H fi1if • | T Y i if i fY° O\ O O\ O1\ Y X^ / hN. X? / \ / \ X fNYA A!ZhN. A?N y TNYYYf YYYf YOH1 o = 1 O\ o o1025 TJN\^\ Y X^^hN. X? Y A / \ X ^NYA A iZNhX / ?\ / NnNi Y YY if; °I ° = 1 O O1026 X JMX \k^^-NH\ Y X^ / hA X? z\ / \z YNA? A iZhNXA iiN Y:NYr n YYYf i °h1 o = 1 O\ O O\ o A^X1027 x< I JN\^DB1 / 163717029.3 48Docket No. 133186-5032-WODB1 / 163717029.3 49Docket No. 133186-5032-WODB1 / 163717029.3 50Docket No. 133186-5032-WOFormula No. StructureY H 5 I O! H 9H10371O -1O o1HlXYYh? Yr fY I H 91038 f If i f i^T i if i YY1O =1O O^ O *YHs Y < Y i H?H1039 Y1O Y =1'Y oxO W O^ O Y* YHNYr^h? Yf rY i H?1040 f1if i Y * Y i ff Y y Y0 =10^ 0 O\ 01< XHXYNH0O }TN11041NY H S Y Y) I H 9N^Y YNVY T Y ioh° °\0°\ o X^,YjDB1 / 163717029.3 51Docket No. 133186-5032-WODB1 / 163717029.3 52Docket No. 133186-5032-WOFormula No. Structurey YY H j| I H1047 A X. / A A.. N— k. N.' N y YNn YY Yf Y i1 0 A^ 1 0. 0 0. 0 8 YA\ / PO3Na2IZ)o=1048 Y z —! / Q“ / ^'O=\ V-zZT\ AoO= / \ / 1049 z * —Q— / z <—o4,'° — \ / IZ 'o=\Y^ \ )o=— \ ZH 9 YY I H 91050xN\N / N\^NV rN / N^°yA " 1 ~ o 1 o^ o O\ oo=\ZIYf^ H 9 * ] YY!HH \1051 N Nr Y N Y n Y nNz> A1 O A\ ' O\ O O\ O='X|X'H / / \ \H I? * ] j H I?1052 -NYrN^NA^rNArAYN^1 0 1 °\ 0 °\ °=\|s\-NY¥HN^ 9N*A* ] ^ NXrX i¥HNvA 9 / 1053 1 O 1 O\ 0 O\ 0 AAST NHo1054 A / hA? * <*rk / \ ^ ^N—Y Y Y i\ ^hN. A?\z Nn:Nn n ^ Yi i1 O 1 0^ 0 0^ 0 YADB1 / 163717029.3 53Docket No. 133186-5032-WODB1 / 163717029.3 54Docket No. 133186-5032-WODB1 / 163717029.3 55Docket No. 133186-5032-WO Formula No. Structure7 Y H? J O 1 H T2zN Y YNAA;106601 O 1 O\ O O \ ^\V NHo1067 A. A / N.. NA A, N. AfN Y;NY n;01 O A\ ' °\ O °x O Ax=\V NHo\ / K / / X k,0 X I Hn 9 \ ' > / II Hn y1068 X / °\^X^k, A / N. Xk,«A ^X / N— \ A. N. A=x\ rNn;Njk n n; °o 1 o 1 °\ O °\ OM X X N J / x k.0nr H 9 \ > iHy1069 A. A / N. / ^.,<\ / X / NA A, N. A,zN Y;Njl n n;01 O A\ 1 °\ O O\ Ou. j o1070 H 9 \ 7 I H Jf °Y^NY A Y YNT YY A yO 1 O Ax 1 °x O °x O X / Az x J oAAHo Y> i H1071 Y^NYNA Y YNY YYyO 1 O A\ 1 °\ 0 °x ° ksDB1 / 163717029.3 56Docket No. 133186-5032-WO Formula No. StructureY "? V O 1Hn'V-O 1072V° ° °\ O °\ ovu1073v°0zx o^ o o^ o1074v° 1 ° ^Y 1 0^ o ov°" "° u Y H 1 1 O I H1075y VO ^1O YY1T O\Y O W O\ O ^0Y H 5 Y O I H 91076 °<^ NVYXYI^NYVYNH2V°00^ 0 O\ 0vuY H S T O I H1077 °^ ANYN^NY\NY4O V°0°\ o °\ o X Y NHoDB1 / 163717029.3 57Docket No. 133186-5032-WO Formula No. Structurei Q1078 YYH? i iA A -N— AZHNK ^ )Yv'Nn;Ni^ n YY n i \ ii yNH 1 0 1 0^ 0 0^ 0i o1079 YY H 9 YY i H YY °^^NAYNYXN-VV TYY YY “J™ 1 0 1 0^ 0 0^ 0 YYAY. j o1080A / M YYh? T ' V ihYrNA ] / TN—; ^M N^^ J ^ []NA jA [ / TNK / y ll1 0 1 0 0^ 0. j oYY H 9 nr i H1081 Y YNYyNH 1 O 1 0\ 0 0\ 0. j oYY H 9 Yr ( / i H Yr1082oy^N\N'YN;YYN-~L~ 1 o 1 o YY oNYi QA? YYhA II YY ^\ / YN—Y A I. N HKY JY1083 ' N y; N' Y n n i1 O ' °\ O °\ O Y-DB1 / 163717029.3Docket No. 133186-5032-WO Formula No. Structure1084VNH0Y\ O\ 0 °1085""L~1010^ 0 0^ 0u. v H1086? V O ihfui0zY °\ 0 °\ 0 ^Y^u1087VNH° Y\ 0^ 0 0^ 0 ^Y^vu1088~-L~-1O1O\ O O\ oTJ1089 A / N Y\hNY? / VVY ONV i HTNY r-YV-OW0YY 0\ 0 0\ 0u1090VNH' ° / Y 1 0\ 0 °\ 0VDB1 / 163717029.3Docket No. 133186-5032-WOFormula No. Structure10911 \ Qz— / 1 / YhI?092 AY\o=\ ^7 iA «AhY YA YY1o \1o. o ex oA Y>0A o0AAz / —Y IY Hn 9 * T '° — \ / ' / II Hn. N— AAA. A, 1093 i ^ N [T No=\ [T [T o yNH 1 0 ' °\0\"- Z °\ ° io— ^o=\ 0Y O ziH? T I H / =\ \ o — / xH1094Nn >Nn n A ( ' —\ / / 0"-L- I o i °\0°\ ° i 0 3 / " YI " Hn 9 * T ' / II HnAk, -A / N. A „,zA N— \ A / N.. A1095FN [T Y^ N jT jT / \ o1 o / Y 1 o^ o < A o i0H I? i H o’ A zN^ A A J. N. A1096Nn ‘Nn nNH2VNH101 O\ O O\ OvMDB1 / 163717029.3 60Docket No. 133186-5032-WOFormula No. StructureH I? | H I?1097 y N y TNn;NH2Y 1 0 A\ 1 oxo 0^ 0u1098 k oAA^ H 9 * T I H ^H2 AZN. A.. A, N— k / k AxN Y;Njk n kA n Y10990Y 1 o ^A 1 oxo o^ o A^\Y NHo|H|HY H J | O I H1100OH OH 1 O ^A 1 O\ O O\ Of' ro - M OH OH YH; Y 0 iHn> 1101 kA N Y YnkA n kA n YNOH OH 1 O A\ ' °\ O °\ O YA.YJ> \ H fl T O! H? A1102 | II - | A II A II -0o °\ o YA,MDB1 / 163717029.3 61Docket No. 133186-5032-WOFormula No. Structure1103 Yhi i O if if X T 100O\ O O\ OMA. Y -A ^HN. A s? V A1k> A i,c. x?x 1104HY X T i °° Y\ °\ ° °\ ° YAu1105. YH9 Y1O i k0 / \ O\ O O\ 0 AA110610 °\ 0 °\ 01107101O\ 0 O\ 01108101O\ 0 O\ 01109k^0 R / f1Y O\Y O ^^ OJ\Y 0 °'m kQYADB1 / 163717029.3 62Docket No. 133186-5032-WO Formula No. Structure1110 Y1° / Y10-A 0 °-V ° mm i0 10 0^ 0 %111217 Y H FT T O i H n1113 VV0'Y YY YVX0\ O 0\ 0M7HH O 1 H n11140°\ o °\ ou7 1 H S Y O 1 H n1115AA0 NY^^XNV YNYN°\ 0 0^ 01116° 0^ 0 0^ 0uDB1 / 163717029.3 63Docket No. 133186-5032-WOFormula No. Structure7 OhH i O i H n1117 Y i s f i Y X T iNo °\ ° o^ ou1 \ Z H? T O I H1118 YX oYYT °\Y °A o^Yo W1119~4™ o10\ 0 0\ 0MXX H? I O 1 H n1120 YX YA YA Y'A11210°\ o °\ oi / N'X4 -p" M1122 I H 9 I H YxH,NY AN\Nk<NXYN^... I0>-^i S A1Si / N> ZS0. >s1123 / Y " i T H YXi 5 x i x SDB1 / 163717029.3 64Docket No. 133186-5032-WO Formula No. Structure11240 / \ / °0U O '1125i 5 A1 / J SA >HH? Y I1126° A""- ' °1127 oX w wo YY 1 o oxoU H YA >HHS? Y I o i H n> 11280 1O 0u1129Y H H V 6 1 "NA T f T Y Y ¥0O\ 0 °X 0 WI QH1130 / YH5 i 6 i Ho1O\ O O^ O1131, Y H 2 Y1O I H YY^ i o10\ 0 0\ 0DB1 / 163717029.3 65Docket No. 133186-5032-WOFormula No. Structure1132 Y H? Y I H f0O\ 0 01 OH1133 / YHs Y d iHio1O\ O 01134, YHu V d i " io1ox0 0^ 01135 z YHjY A IH° 0^ 0 0^ 0 YA1136, YH 6 I "AA0ArY A 'YYA 0\ o °\ o \A| OH1137 A / YVHU Y A 10AA O^\ 0Y H0\V 0 ^ \^Y1138 V H § V A I Ho10\ 0 0\ 0 YA1139A7A Y H N 1 O I H0NAT^NAAN^A fYY °\ o °\ oF^AADB1 / 163717029.3 66Docket No. 133186-5032-WOFormula No. Structure1 QH1140 / YH; Y O IHfo Ox0 0^ 01141 Y H » V 6 [ " 1A > fYY Y Y " AAl° / A °\ O 0^ 0p^AA1142A °Y Z\ X 0A^ 0Y 0^V0 A zAQA-1143A0Y / A X 0A\ 0Y 0\V O Y zkYAF1144 vHJY 0 ihjfH0°\0°\0 / \AF1 QH11450AA °\ 0 °\ 0 ZAA- 1 ^NH1146 YHu 1! H fT A YfA r0zA O\ O Y 0\Y 0FYYDB1 / 163717029.3 67Docket No. 133186-5032-WOFormula No. StructureI NH21147 7 Y H 5 Y < 7 I H fo10 O\ 0I ^NH1148 YHS 1 6 I H f1o10. 0 0. 0 A A1 NH21149 7 Y H H 1 O I H f AV o ^1^ 0^ 0NAV^A 0^ 01150 Y H! Y < 7 I H fo10 0\ 01 HlA1151 7 Y H J I O! H fA XA^N. A A / \ZNA A ^NX / X / X YYr i YTY YAr° °\ ° °\0F^A^1152 Y H J | Y)! H fo ^x\10^ 0 0\ 0FA^A1 HlA / YHM 6 1 H f 1153° ^A °\0< A oF^A68 DB1 / 163717029.3Docket No. 133186-5032-WO

[0164] In some embodiments, D of the antibody -drug conjugate (ADC) of formula (I) is selected from any one of formula 1001-1157, or a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0165] In embodiments, the antibody-drug conjugate has the following formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds to CUB Domain- Containing Protein-1 (CDCP1);L is a bond or a linker;D is a drug moiety comprising an auristatin; andn is an integer from 1 to 20;wherein the drug moiety is selected from any one of formula 1001-1157, or a stereoisomer, or a pharmaceutically acceptable salt thereof.DB1 / 163717029.3 69Docket No. 133186-5032-WOLinkers

[0166] In aspects, a drug moiety is attached, either directly or indirectly, to an antibody or antigen binding fragment thereof to provide an antibody-drug conjugate (ADC) of the disclosure. In embodiments, a drug moiety (, D) is attached to an antibody or antigen binding fragment thereof (, Ab), either through a bond or a linker (, L), to provide an antibody-drug conjugate (ADC) of formula (I). In embodiments, L of the antibody-drug conjugate (ADC) of formula (I) is a bond or a linker. In some embodiments, L of the antibody-drug conjugate (ADC) of formula (I) is a bond. In a non-limiting example, when L is a bond, the drug moiety is directly attached to the antibody or antigen binding fragment thereof. In some embodiments, L of the antibody-drug conjugate (ADC) of formula (I) is a linker. In a non-limiting example, when L is a linker, the drug moiety is indirectly attached to the antibody or antigen binding fragment thereof. In one aspect, the disclosure provides linkers useful within the antibody-drug conjugates (ADCs) of formula (I). Any linker suitable for attaching a drug moiety to an antibody or antigen binding fragment thereof is contemplated by the present disclosure, as would be understood by one of ordinary skill in the art.

[0167] In some embodiments, L of the antibody-drug conjugate (ADC) of formula (I) is a bond or a linker having 1-200 nonhydrogen atoms selected from C, N, O, S, or halogen, and optionally incorporating alkyl, ether, oxo, carboxyl, carboxamide, carboxamidyl, ester, urethanyl, branched, cyclic, unsaturated, amino acid, heterocyclyl, aryl or heteroaryl moieties. In some embodiments, the linker is unbranched or branched, flexible or rigid, short or long, and optionally incorporates any combination of moieties as deemed useful.

[0168] In some embodiments, the linker includes an alkylene chain comprising a number of repeating alkylene units (, -CH2-) ranging from 1 to 20. In some embodiments, the alkylene chain is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbons in length. In some embodiments, other moieties such as substituted aromatic or heteroaromatic moieties are used to enhance rigidity or provide synthetically accessible sites on substituents therein for attaching to the alkylene or other portion of the linker or to the drug moiety.

[0169] In some embodiments, the linker comprises a hydrophilic moiety or at least a portion of the linker has a hydrophilic region. In some embodiments, the hydrophilic moiety or hydrophilic region of the linker comprises polyethylene glycol; polyalkylene glycol; one or more sugar moieties (e.g., oligosaccharide); one or more amino acid moieties (e.g., polypeptide); polysarcosine; C2-C12alkylene substituted with 1 to 10 groups selected from -PO(OH)2, -DBl / 163717029.3 70Docket No. 133186-5032-WOPO(OCH3)2, -PO(OCH3)2, -PO(OCH2CH3)2, -0-P0(0H)2, -O-PO(OCH3)2, -O-PO(OCH3)2, and / or -O-PO(OCH2CH3)2; or a combination thereof.

[0170] In some embodiments, at least a portion of the linker has a polyalkylene oxide (e.g., polyethylene glycol) polymeric region. In a non-limiting example, a polyalkylene oxide polymeric region is capable of enhancing solubility of the drug moiety. In some embodiments, the linker has a repeating unit of ethylene glycol. In some embodiments, the linker has a number of repeating ethylene glycol units ranging from about 1 to about 50, or any number therebetween. In some embodiments, the linker has a number of repeating ethylene glycol units ranging from 1 to 50, or any number therebetween. In some embodiments, the linker includes about 1 to about 24 ethylene glycol units. In some embodiments, the linker includes 1 to 24 ethylene glycol units. In some embodiments, the linker includes about 1 to about 12 ethylene glycol units. In some embodiments, the linker includes 1 to 12 ethylene glycol units. Nonlimiting examples of commercially available ethylene glycol groups (polyethylene glycol, PEG) suitable in the linker include H2N-dPEGs-C(O)OH, having a discrete (“d”) polyethylene glycol having 8 ethylene glycol repeating units. Non-limiting examples of other discrete PEG units are commercially available and known to one of skill in the art, such as by Advanced ChemTech.

[0171] In some embodiments, at least a portion of the linker has a poly sarcosine polymeric region. In a non-limiting example, a polysarcosine polymeric region is capable of enhancing solubility of the drug moiety. In some embodiments, the linker has a repeating unit of sarcosine. In some embodiments, the linker has a number of repeating sarcosine units ranging from about 1 to about 50, or any number therebetween. In some embodiments, the linker has a number of repeating sarcosine units ranging from 1 to 50, or any number therebetween. In some embodiments, the linker includes about 1 to about 25 sarcosine units. In some embodiments, the linker includes 1 to 25 sarcosine units. In some embodiments, the linker includes about 1 to about 12 sarcosine units. In some embodiments, the linker includes 1 to 12 sarcosine units. Additional non-limiting examples of hydrophilic moieties for including in linkers, such as polysarcosine, can be found in U. S. Application Publication No. US 2023 / 0091510 Al, which is incorporated by reference herein in its entirety.

[0172] In some embodiments, at least a portion of the linker includes one or more amino acid moieties. In a non-limiting example, one or more amino acid moieties provides enhanced solubility for the drug moiety and / or provides amino acid sequences to enhance target binding, enhance compatibility with an antibody or antigen binding fragment thereof, and / or enhance target binding recognition. In some embodiments, the linker includes one or more amino acid DBl / 163717029.3 71Docket No. 133186-5032-WOmoieties that provide a suitable substrate motif for a protease. In a non-limiting example, when a set of amino acid moieties are incorporated into the linker that provide a substrate motif specific for a selected protease, the drug moiety may be released from a target bound conjugate to provide localized cytotoxic effects. Any amino acid moieties are contemplated by the disclosure, including but not limited to canonical or non-canonical amino acids, or non-natural or non- proteinogenic amino acids. Non-limiting examples of non-natural or non-proteinogenic amino acids include homo-alanine (a-Aminobutyric acid), norvaline, and norleucin.

[0173] In embodiments, L is a linker comprising an amino acid sequence having 1 amino acid moiety selected from alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), valine (Val), selenocysteine, homoalanine (a-Aminobutyric acid), norvaline, and norleucin. In embodiments, L is a linker comprising an amino acid sequence having 2 amino acid moieties selected from Vai-Ala, Tyr- Arg, Phe-Arg, Val-Gln, Val-Cit, Asn-Asn, Tyr-Met, Leu-Gin, Val-Arg, Met-Thr, Phe-Gln, Thr- Thr, Val-Thr, Ala-Ala, Val-Met, Leu-Met, Ala-Asn, D-Val-D-Gln, D-Ala-D-Ala, and Phe-Met. In embodiments, L is a linker comprising an amino acid sequence having 3 amino acid moieties selected from alanine-alanine-alanine, valine-alanine-alanine, glutamic acid-valine-citrulline, and valine -lysine -glycine. In embodiments, L is a linker comprising an amino acid sequence having 4 amino acid moieties selected from glycine-glycine-phenylalanine-glycine, glutamic acid-aspartic acid-phenylalanine -tryptophan, glycine-phenylalanine-leucine-glycine, and alanine-leucine- alanine -leucine

[0174] In some embodiments, L of the antibody-drug conjugate (ADC) of formula (I) is a bond or a linker comprising one or more groups selected from C₁-C₆ alkyl, C=O, -NH-, ethylene glycol, optionally 2-50 or 2-10 ethylene glycol units, valine-citrulline (val-cit), 6- maleimidocaproyl (me), 6-succinimidylcaproyl, 6-(2,5-dioxo-3λ3-pyrrolidin-1-yl)caproyl, methoxy-polyethylene glycol maleimide 6 (MalPeg6), p-aminobenzylcarbamate (PABC), dimethylaminoethanol (DMAE), 3-maleimidopropanoyl (MP), 3-succinimidylpropanoyl, 3-(2,5-dioxo-3λ3-pyrrolidin-1-yl)propanoyl, hydrolyzed Peg-maleimides, hydrolyzed maleimide, hydrolyzed succinimide, p-aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2 -pyridylthio) pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl) cyclohexane- Icarboxylate (SMCC), N-Succinimidyl (4-iodo-acetyl) aminobenzoate (SIAB), 6-maleimidocaproyl-valine-citrulline-p- aminobenzyloxycarbonyl (mc-val-cit-PAB), and 6-maleimidocaproyl-valine-citrulline-p-DBl / 163717029.3 72Docket No. 133186-5032-WOaminobenzylcarbamate (mc-val-cit-PABC), an amino acid, optionally (D)-valine, (L)-valine, (D)-alanine, and / or (L)-alanine, an amino acid sequence, optionally valine -alanine (Vai-Ala), alanine-phenylalanine (Ala-Phe), alanine-alanine-alanine (Ala- Ala- Ala), or glycine-glycine- phenylalanine-glycine (Gly-Gly-Phe-Gly), and maleimide.

[0175] In some embodiments, L is a linker comprising or consisting of the formula:-[CH2CH2O]p-XAA-, wherein XAA is an amino acid sequence, and p is an integer from 0 to 50. In some embodiments, p is an integer from 0 to 40. In some embodiments, p is an integer from 0 to 30. In some embodiments, p is an integer from 1 to 24. In some embodiments, p is an integer from 1 to 20. In some embodiments, p is an integer from 1 to 10.

[0176] In some embodiments, L is a linker comprising or consisting of the formula:-[CH2CH2O]p-(CH2)1-10-C(O)-XAA-, wherein XAA is an amino acid sequence, and p is an integer from 0 to 50. In some embodiments, p is an integer from 0 to 40. In some embodiments, p is an integer from 0 to 30. In some embodiments, p is an integer from 1 to 24. In some embodiments, p is an integer from 1 to 20. In some embodiments, p is an integer from 1 to 10.

[0177] In some embodiments, L is a linker comprising or consisting of the formula:-HN-PEG-C(O)-XAA-, wherein PEG has 1-50 ethylene glycol units, and XAA is an amino acid sequence. In some embodiments, PEG has 1-24 ethylene glycol units.

[0178] In some embodiments, L is a linker comprising or consisting of the formula:-HN-PEG-(CH2)1-10-C(O)-XAA-, wherein PEG has 1-50 ethylene glycol units, and XAA is an amino acid sequence. In some embodiments, PEG has 1-24 ethylene glycol units.

[0179] In some embodiments, L is a linker comprising or consisting of the formula:-[CH2]0-12-XAA-, wherein XAA is an amino acid sequence; and the linker includes 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 -CH2- units.

[0180] In some embodiments, the linker also includes a variety of other groups that connect the ethylene glycol portion of the linker to the amino acid sequence of the linker, or that connect the alkylene chain portion of the linker to the ethylene glycol portion or amino acid sequence of the linker, or that connect any portion of the linker to any other group or portion of the linker, that connect any portion of the linker to the antibody or antibody-binding fragment thereof (z. e., Ab) and / or drug moiety (z'.e., D) of the antibody-drug conjugate (ADC) of formula (I). For example, the amino acid sequence can be connected to the drug moiety via a 4-amino benzyl carboxylate group. In some embodiments, the ethylene glycol portion ca be directly linked to anDBl / 163717029.3 73Docket No. 133186-5032-WOantibody or antibody-binding fragment. In some embodiments, the linker comprises or consists of the formula:! H H|— N— PEG8— C(O)— Val-Ala-NIn some embodiments, the HN group is directly linked to the antibody or antigen binding fragment thereof (i.e., Ab) of the antibody-drug conjugate (ADC) of formula (I).

[0181] In some embodiments, L is a linker comprising or consisting of:is an amino acid sequence; and K2 is -[CH2CH20]o-5o-[CH2]o-i2-C(0)-, -[CH2CH20]o-so-, or -[CH2]o-i2-. In some embodiments, the linker is attached to the antibody or antibody-binding fragment thereof and the drug moiety in either direction. In some embodiments, the linker is (i), (ii), (iii), (iv), (vi), (viii) or (ix).

[0182] In some embodiments, L is a linker comprising a cleavable spacer moiety. In a nonlimiting example, a cleavable spacer moiety of the linker provides enhanced activity and / or properties before, after, and / or while the drug moiety (i.e., D) is conjugated to the antibody or antigen binding fragment thereof (i. e., Ab) through the linker. In embodiments, the cleavable spacer moiety provides an enhancement of hydrophilicity of the antibody-drug conjugate (ADC) compared to the antibody-drug conjugate (ADC) without the cleavable spacer moiety. Any cleavable spacer moiety is contemplated by the present disclosure, provided that the cleavable spacer moiety is capable of cleavage and / or degradation to provide a free (unconjugated) drug moiety.

[0183] In some embodiments, L is a linker comprising a moiety of the following formula:DBl / 163717029.3 74Docket No. 133186-5032-WOwherein:O O Oi l-Q-P H-l M |— O-P H-O-P H— | I A is selected from a bond, -OC(=O)-, OH?OH OH,OH OH OH -OC(=O)N(CH3)CH2CH2N(CH3)C(=O)-, and -OC(=O)N(CH3)C(R')2C(R')2N(CH3)C(=O)-;W is selected from -CH2O-, -CH2N(R')C(=O)O-, -NHC(=O)CH2NHC(=O)O-, -CH2N(X-R2)C(=O)O-, -C(=O)N(X-R2)-, -CH2N(X-R2)C(=O)-, -C(=O)NR'-, -CH2NR'C(=O)-, -CH2NR'C(=O)NH-, -CH2NR'C(=O)NR'-, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O)2NH-, -NHS(O)2-, -C(=O)-, -C(=O)O-, and -NH-;X is a bond, triazolyl, or -CH2-triazolyl;R2is a hydrophilic moiety selected from polyethylene glycol, polyalkylene glycol, a sugar, an oligosaccharide, a polysarcosine, a polypeptide, and C2-C6 alkyl substituted with 1 to 3 O OsII | II|— o— p— OH | — p— OHOH or OH groups; andeach R' is independently at each occurrence selected from H, C₁-C₆ alkyl, and C3-C8 cycloalkyl.

[0184] In some embodiments, L is a linker comprising a moiety of the following formula:wherein:W is selected from -CH2O-, -CH2N(R')C(=O)O-, -NHC(=O)CH2NHC(=O)O-, -CH2N(X-R2)C(=O)O-, -C(=O)N(X-R2)-, -CH2N(X-R2)C(=O)-, -C(=O)NR'-, -CH2NR'C(=O)-,DBl / 163717029.3 75Docket No. 133186-5032-WO-CH2NR'C(=O)NH-, -CH2NR'C(=O)NR'-, -NHC(=O)-, -NHC(=O)O-, -NHC(=O)NH-, -OC(=O)NH-, -S(O)2NH-, -NHS(O)2-, -C(=O)-, -C(=O)O-, and -NH-;X is a bond, triazolyl, or -CH2-triazolyl;R2is a hydrophilic moiety selected from, a sugar, a polypeptide, and C2-Ce alkyl i II; II |— o— p— OH I — p— OH substituted with 1 to 3 OH or OH groups; each R' is independently at each occurrence selected from H, C₁-C₆ alkyl, and Cs-Cs cycloalkyl;Rlais selected from H, -CH3, and -CH2CH2C(=O)OH;Rlbis selected from H, -CH3, -CH2CH2NHC(=O)OR2b, -CH2CH2NHC(=O)R2b, and -CH2CH2C(=O)OR2b;Rib is H or Ci-4 alkyl optionally substituted with OH or Ci-4 alkoxy; andeach of m, q, and r is an integer from 2 to 25.

[0185] In some embodiments, L is a linker comprisingO, or Su?wherein Rais selected at each occurrence from hydrogen and optionally substituted alkyl, and Su is a carbohydrate moiety selected from betaglucuronide, beta-galactose and beta-glucose, or isomers thereof.

[0186] In some embodiments, L is a linker comprising one or more groups selected from:DBl / 163717029.3 76Docket No. 133186-5032-WO

[0187] Additional non-limiting examples of cleavable moieties can be found in Gavriel et al., Polym. Chem. 13:3188 (2022), which is incorporated by reference herein in its entirety.

[0188] In embodiments, L is a bond or a linker comprising one or more groups selected from succinimide, an oxime, a bisulfone, a heterocycle, optionally a triazole or an isoxazolidine, an amide, and a thioether, an alkenyl phosphorous group, and an alkyl phosphorous group.

[0189] In some embodiments, L is a linker comprising a reactive moiety that has reacted with a functional group of an antibody or antigen binding fragment thereof. In embodiments, L is a linker comprising succinimide (z.e., a succinimidyl moiety, “2,5-dioxo-3λ3-pyrrolidin-1-yl”):

[0190] In some embodiments, L is a linker comprisingIn some embodiments, Lis a linker comprising. In some embodiments, L is a linker comprisingOIn some embodiments, L is a linker comprising. In someembodiments, L is a linker comprisingIn some embodiments, LDBl / 163717029.3 77Docket No. 133186-5032-WO

[0191] In some embodiments, L is a linker comprising a heterocycle, optionally wherein the heterocycle is formed by a cycloaddition (e.g., click chemistry) between two or more unsaturated moieties. In some embodiments, the heterocycle is fused to one or more additional rings, including but not limited to a cyclooctynyl ring. In some embodiments, L is a linker comprising a triazole (triazolyl) moiety, optionally wherein the triazole (triazolyl) moiety is formed by a cycloaddition reaction (e.g., click chemistry) between an azide and an alkyne. In some embodiments, L is a linker comprising an isoxazolidine (isoxazolidinyl) moiety, optionally wherein the isoxazolidine (isoxazolidinyl) moiety is formed by a cycloaddition of a nitrone and an alkyne. In some embodiment, the alkyne is a cyclooctynyl group. Non-limiting examples of cyclooctynyl groups include dibenzocyclooctynye (DBCO) and derivatives thereof. In some embodiments, the cyclooctynyl ring is fused to one or more additional rings, including but not limited to cycloalkyl rings and / or heterocycloalkyl rings.DB1 / 163717029.3 78Docket No. 133186-5032-WO, wherein R is hydrogen or a substituent and n is an integer from 0 to 8. See, for example, US 20150320882, US 20230102685, US 20160107999, US 20170008858, US 20170298145, and US 20230099074 for additional examples of cyclooctynyl groups, all of which are incorporated by reference herein in their entireties.

[0193] In some embodiments, U is a linker comprising an oxime group. In some embodiments, U is a linker comprising an oxime group of the formula' ', wherein Ui is a linker moiety including but not limited to any linker groups disclosed herein. In some embodiments, Ui comprises or consists of a substituted or unsubstituted alkyl group. In some yN^(CH2)n-( embodiments, U is a linker comprising an oxime group of the formula ', and DBl / 163717029.3 79Docket No. 133186-5032-WOn is an integer from 1 to 10 (e.g., n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). In embodiments, Li comprises or consists of one or more polyethyleneglycol (PEG) groups. In some embodiments, L yN^(CH2CH2O)n-^is a linker comprising an oxime group of the formula', and n is an integer from 1 to 10 (e.g., n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10). See, for example, US 20230295320, US 11773150, US 20160052966, all of which are incorporated by reference herein in their entireties.

[0194] In some embodiments, L is a linker comprising an alkenyl phosphorous group. In some embodiments, L is a linker comprising an alkenyl phosphorous group of the formula, wherein R is alkyl, aryl, or a polyethyleneglycol (PEG) group comprising 1 to 10 ethylene glycol units. In some embodiments, L is a linker comprising an alkyl phosphorous group. In some embodiments, L is a linker comprising an alkyl phosphorous group of theformula, wherein R is alkyl, aryl, or a polyethyleneglycol (PEG) group comprising 1 to 10 ethylene glycol units. See, for example US 20230330258 and US 20230158154, both of which are incorporated by reference herein in their entireties.

[0195] In embodiments, L is a bond or a linker selected from:DBl / 163717029.3 80Docket No. 133186-5032-WO[CHzCHzO],.^wherein, XAAis an amino acid sequence having 1 to 5 amino acid moieties.

[0196] In embodiments, XAA is selected from alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), valine (Val), selenocysteine, homo-alanine (a-aminobutyric acid), norvaline, norleucine, Val-Ala, Tyr-Arg, Phe-Arg, Val-Gln, Val-Cit, Asn-Asn, Tyr-Met, Leu-Gin, Val-Arg, Met-Thr, Phe-Gln, Thr-Thr,DBl / 163717029.3 81Docket No. 133186-5032-WOVal-Thr, Ala-Ala, Val-Met, Leu-Met, Ala-Asn, D-Val-D-Gln, D-Ala-D-Ala, Phe-Met, alanine- alanine-alanine, valine-alanine-alanine, glutamic acid-valine-citrulline, valine-lysine-glycine, glycine-glycine-phenylalanine-glycine, glutamic acid-aspartic acid-phenylalanine-tryptophan, glycine-phenylalanine-leucine-glycine, and alanine-leucine-alanine-leucine.

[0197] In some embodiments, XAA is selected from:

[0198] In some embodiments, XAA is selected from:

[0199] In some embodiments, XAA is selected from:

[0200] In embodiments, L is a bond or a linker selected from:DBl / 163717029.3 82Docket No. 133186-5032-WODB1 / 163717029.3 83Docket No. 133186-5032-WO'^OH OHOH

[0201] In some embodiments, the linker comprises or consists of the formula:

[0202] In some embodiments, the linker comprises or consists of the formula:

[0203] In some embodiments, the linker comprises or consists of the formula:DBl / 163717029.3 84Docket No. 133186-5032-WO

[0204] In some embodiments, the linker comprises or consists of the formula:

[0205] In some embodiments, the linker comprises or consists of the formula:o

[0206] In some embodiments, the linker comprises or consists of the formula:oDB1 / 163717029.3 85Docket No. 133186-5032-WO

[0207] In some embodiments,L is

[0208] In some embodiments,L is

[0209] In some embodiments, L is

[0210] In some embodiments, Lismoiety of formula 1010:DBl / 163717029.3 86Docket No. 133186-5032-WO

[0212] In some embodiments, n of the antibody-drug conjugate (ADC) of formula (I) is an integer from 1 to 25. In embodiments, n is an integer from 1 to 20. In embodiments, n is an integer from 1 to 10. In embodiments, n is an integer from 4 to 8. In embodiments, n is an integer from 2 to 8. In embodiments, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25. In embodiments, n is 25 or greater. In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 3. In embodiments, n is 4. In embodiments, n is 5. In embodiments, n is 6. In embodiments, n is 7. In embodiments, n is 8. In embodiments, n is 9. In embodiments, n is 10.Antibodies

[0213] In one aspect, the disclosure provides antibodies and antigen binding fragments thereof useful within the antibody-drug conjugates (ADCs) of formula (I). In some embodiments, the antibody-drug conjugate (ADC) of formula (I) comprises a means for binding CUB Domain-Containing Protein-1 (CDCP1), such as an antibody or antigen binding fragment thereof that binds to CDCP 1. In some embodiments the antibody and / or antigen binding fragment thereof is an antibody or antigen-binding portion thereof that is specific for CDCP 1.CUB domain-containing protein 1 (CDCP1)

[0214] CDCP1 (HGNC: 24357; NCBI Entrez Gene: 64866; Ensembl: ENSG00000163814; UniProtKB / Swiss-Prot: Q9H5V8) has a large extracellular domain (665 amino acids in size) containing three CUB domains that mediate protein-protein interactions and are likely involved in cell adhesion and interaction with the extracellular matrix. The CDCP 1 gene has been found to be strongly expressed in cancer, and has been previously disclosed as a therapeutic target in at least WO 2020 / 097336 and WO 2018 / 112334, which are herein incorporated by reference in their entireties.DBl / 163717029.3 87Docket No. 133186-5032-WO

[0215] In some aspects, the disclosure provides antibodies or antigen binding fragments that bind to the CDCP 1 protein having sequences as disclosed in Table 1.Table 1. Exemplary CDCP1 sequences.SEQ ID NO: Sequence name Amino acid sequence9 CUB domain- contain! ng MAGLNCGVSIALLGVLLLGAARLPRGAEAFEIALPRESNITVLIKLGTPT protein 1 isoform 1 LLAKPCYIVISKRHITMLSIKSGERIVFTFSCQSPENHFVIEIQKNIDCM precursor [Homo SGPCPFGEVQLQPSTSLLPTLNRTFIWDVKAHKSIGLELQFSIPRLRQIG sapiens J PGESCPDGVTHSISGRIDATWRIGTFCSNGTVSRIKMQEGVKMALHLPW FHPRNVSGFSIANRSSIKRLCIIESVFEGEGSATLMSANYPEGFPEDELM TWQFWPAHLRASVS FLNFNLSNCERKEERVEYYI PGSTTNPEVFKLEDK QPGNMAGNFNLSLQGCDQDAQSPGILRLQFQVLVQHPQNESNKIYWDLS NERAMSLTIEPRPVKQSRKFVPGCFVCLESRTCSSNLTLTSGSKHKISFL CDDLTRLWMNVEKTISCTDHRYCQRKSYSLQVPSDILHLPVELHDFSWKL LVPKDRLSLVLVPAQKLQQHTHEKPCNTSFSYLVASAIPSQDLYFGSFCP GGSIKQIQVKQNISVTLRTFAPSFQQEASRQGLTVSFIPYFKEEGVFTVT PDTKSKVYLRTPNWDRGLPSLTSVSWNISVPRDQVACLTFFKERSGWCQ TGRAFMIIQEQRTRAEEIFSLDEDVLPKPSFHHHSFWVNISNCSPTSGKQ LDLLFSVTLTPRTVDLTVILIAAVGGGVLLLSALGLIICCVKKKKKKTNK GPAVGIYNDNINTEMPRQPKKFQKGRKDNDSHVYAVIEDTMVYGHLLQDS SGSFLQPEVDTYRPFQGTMGVCPPSPPTICSRAPTAKLATEEPPPRSPPESESEPYTFSHPNNGDVSSKDTDIPLLNTQEPMEPAETable 1A. Exemplary CDCP1 immunogenic peptide sequencesSEQ Sequence name Amino acid sequenceID NO:556 Immunogenic peptide for SKHKISFLCDDLTRLWMNVEKTISCTDHRYCQRKSYSLQVPSDILHLPVE polyclonal antibody LHDFSWKLLVPKDRLSLVLVPAQKLQQHTHEKPCNTSFSYLVASAIPSQD HPA010978 LYFGSFCPGGSIKQIQVKQ557 Immunogenic for polyclonal GFSIANRSSIKRLCIIESVFEGEGSATLMSANYPEGFPEDELMTWQFWP antibody HPA010979 AHLRASVSFLNFNLSNCERKEERVEYYIPGSTTNPEVFKLEDKQPGNMAGNFNLSLQGCDQDAQSPGILRLQFQVLVQHPQNESNKIYWDLSNERA

[0216] In some aspects, the CDCP1 is human CDCP1. In some aspects, the CDCP1 is cynomologus monkey (cyno) CDCP1. In some aspects, the CDCP1 is mouse CDCP1. In some aspects, the CDCP1 is primate CDCP1. An exemplary CDCP1 sequence is provided in Table 1.

[0217] The immunoglobulin disclosed herein can be of any type (e.g., IgG, IgE, IgM, IgD, and IgA), class (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2) or subclass of immunoglobulin molecule. The immunoglobulins can be derived from any species. In one aspect, however, the immunoglobulin is of human, murine, or rabbit origin.

[0218] The antibodies and antigen binding fragments thereof are characterized by unique sets of CDR sequences, specificity for CDCP1, and are useful in cancer immunotherapy asDBl / 163717029.3 88Docket No. 133186-5032-WOmonotherapy or in combination with other anti-cancer agents. More specifically, the disclosure relates to antibodies that bind to human CDCP1, and to their use to target CDCP1 in tumor cells.

[0219] In some aspects, a CDCP1 antibody or antigen binding fragment thereof comprises one or more CDRs and / or heavy chain (HC) variable regions and / or light chain (LC) variable regions as listed in Table 2A, Table 2B, and / or Table 3.

[0220] In some aspects, the antibodies or antigen binding fragments thereof comprise a set of six complementarity determining region (CDR) sequences selected from the group consisting of three CDRs (CDRH) of a heavy chain (HC) variable region (VH) selected from SEQ ID NOs: 1; 15; 23-246; 471-518 or expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249, and three CDRs (CDRL) of a light chain (LC) variable region (VL) selected from SEQ ID NOs: 5; 19; 250-467; 519-555 or expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470. Alternatively, the antibodies or antigen binding fragments thereof comprise a heavy chain variable region (VH) and / or a light chain variable region (VL) having at least 90%, 95%, 96%, 97%, 98% or 99% sequence identity to the heavy chain variable region of any one of SEQ ID NOs: 1; 15; 23-246; 471-518 or expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249, and / or the light chain variable region of any one of SEQ ID NOs: 5; 19; 250-467; 519-555 or expressed from a nucleic acid sequence selected from SEQ ID NOs: 468- 470, respectively, provided that the antibody or fragment thereof retains binding to CDCP1.

[0221] In some embodiments, the antibodies or antigen binding fragments thereof comprise a heavy chain variable region comprising CDRH1: SEQ ID NO: 2, CDRH2: SEQ ID NO: 3, and CDRH3: SEQ ID NO: 4; and / or a light chain variable region comprising CDRL1: SEQ ID NO: 6, CDRL2: SEQ ID NO: 7, and CDRL3: SEQ ID NO: 8.

[0222] In some embodiments, the antibodies or antigen binding fragments thereof comprise a heavy chain variable region comprising CDRH1: SEQ ID NO: 12, CDRH2: SEQ ID NO: 13, and CDRH3: SEQ ID NO:14; and / or a light chain variable region comprising CDRL1: SEQ ID NO: 6, CDRL2: SEQ ID NO: 7, and CDRL3: SEQ ID NO: 8.

[0223] In some embodiments, the antibodies or antigen binding fragments thereof comprise a heavy chain variable region comprising CDRH1: SEQ ID NO: 16, CDRH2: SEQ ID NO: 17, and CDRH3: SEQ ID NO:18; and / or a light chain variable region comprising CDRL1: SEQ ID NO: 20, CDRL2: SEQ ID NO: 21, and CDRL3: SEQ ID NO: 22.

[0224] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence that comprises an amino acid sequence with at least about 95%, DBl / 163717029.3 89Docket No. 133186-5032-WOabout 96%, about 97%, about 98%, or about 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence that comprises an amino acid sequence with at least 95%, 96%, 97%, 98%, or 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the antibody or antigen binding fragment thereof retains the binding and / or functional activity of an antibody or antigen binding fragment thereof that comprises the variable heavy chain sequence of SEQ ID NO 1. In some embodiments, the antibody or antigen binding fragment thereof comprises the variable heavy chain sequence of SEQ ID NO: 1 and has one or more conservative amino acid substitutions, e.g., 1, 2, 3, 4, 5, 1-2, 1-3, 1-4 or 1-5 conservative amino acid substitutions in the heavy chain variable sequence. In some embodiments, the one or more conservative amino acid substitutions fall within one or more framework regions in SEQ ID NO: 1 (based on the numbering system of Kabat).

[0225] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the binding protein heavy chain variable region sequence set forth in SEQ ID NO: 1 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable heavy chain sequence as set forth in SEQ ID NO: 1. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence with at least 95%, 96%, 97%, 98%, or 99% sequence identity to the binding protein heavy chain variable region sequence set forth in SEQ ID NO: 1 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable heavy chain sequence as set forth in SEQ ID NO: 1.

[0226] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence that comprises an amino acid sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence that comprises an amino acid sequence with at least 95%, 96%, 97%, 98%, or 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, antibody or antigen binding fragment thereof retains the binding and / or functional activity of a targeting agent, antibody, or antigen binding fragment thereof that comprises the variable light chain sequence of SEQ ID NO: 5. In someDBl / 163717029.3 90Docket No. 133186-5032-WOembodiments, the antibody or antigen binding fragment thereof comprises the variable light chain sequence of SEQ ID NO: 5 and has one or more conservative amino acid substitutions, e.g., 1, 2, 3, 4, 5, 1-2, 1-3, 1-4 or 1-5 conservative amino acid substitutions in the light chain variable sequence. In some embodiments, the one or more conservative amino acid substitutions fall within one or more framework regions in SEQ ID NO: 5 (based on the numbering system of Kabat).

[0227] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the binding protein light chain variable region sequence set forth in SEQ ID NO: 5 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable light chain sequence as set forth in SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence with at least 95%, 96%, 97%, 98%, or 99% sequence identity to the binding protein light chain variable region sequence set forth in SEQ ID NO: 5 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable light chain sequence as set forth in SEQ ID NO: 5.

[0228] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence that comprises an amino acid sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence that comprises an amino acid sequence with at least 95%, 96%, 97%, 98%, or 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the antibody or antigen binding fragment thereof retains the binding and / or functional activity of an antibody or antigen binding fragment thereof that comprises the variable heavy chain sequence of SEQ ID NO 15. In some embodiments, the antibody or antigen binding fragment thereof comprises the variable heavy chain sequence of SEQ ID NO: 15 and has one or more conservative amino acid substitutions, e.g., 1, 2, 3, 4, 5, 1- 2, 1-3, 1-4 or 1-5 conservative amino acid substitutions in the heavy chain variable sequence. In some embodiments, the one or more conservative amino acid substitutions fall within one or more framework regions in SEQ ID NO: 15 (based on the numbering system of Kabat).DBl / 163717029.3 91Docket No. 133186-5032-WO

[0229] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the binding protein heavy chain variable region sequence set forth in SEQ ID NO: 15 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable heavy chain sequence as set forth in SEQ ID NO: 15. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence with at least 95%, 96%, 97%, 98%, or 99% sequence identity to the binding protein light chain variable region sequence set forth in SEQ ID NO: 15 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable heavy chain sequence as set forth in SEQ ID NO: 15.

[0230] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence that comprises an amino acid sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence that comprises an amino acid sequence with at least 95%, 96%, 97%, 98%, or 99%, sequence identity to the amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof retains the binding and / or functional activity of a targeting agent, antibody, or antigen binding fragment thereof that comprises the variable light chain sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises the variable light chain sequence of SEQ ID NO: 19 and has one or more conservative amino acid substitutions, e.g., 1, 2, 3, 4, 5, 1-2, 1-3, 1-4 or 1-5 conservative amino acid substitutions in the light chain variable sequence. In some embodiments, the one or more conservative amino acid substitutions fall within one or more framework regions in SEQ ID NO: 19 (based on the numbering system of Kabat).

[0231] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity to the binding protein light chain variable region sequence set forth in SEQ ID NO: 19 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable light chain sequence as set forth in SEQ IDDBl / 163717029.3 92Docket No. 133186-5032-WONO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable light chain sequence with at least 95%, 96%, 97%, 98%, or 99% sequence identity to the binding protein light chain variable region sequence set forth in SEQ ID NO: 19 comprises one or more conservative amino acid substitutions in a framework region (based on the numbering system of Kabat), and retains the binding and / or functional activity of a binding protein that comprises a variable light chain sequence as set forth in SEQ ID NO: 19.

[0232] In some embodiments, the antibody or antigen binding fragment thereof specifically bind CDCP1. Sequences of exemplary antibodies are shown in WO 2018 / 112334, which is incorporated by reference herein in its entirety. In some embodiments, the ADC is used to treat cancer.Table 2A. Anti-CDCP 1 sequences.SEQ ID SequenceAmino acid sequenceNO: identi tier1 Heavy Chain EVQLLESGGG LVQPGGSLRL SCAASGFTFS NYAMNWVRQAvariable region PGKGLEWVSA ISGGGGSTYY ADSVKGRFTI SRDNSKNTLY(VH) LQMNSLRAED TAVYYCAKES ITMVRGVMDY YGMDVWGQGTTVTVS S2 CDRH1 GFTFSNYAMN3 CDRH2 AISGGGGSTY YADSV4 CDRH3 AKESITMVRGVM DYYGMDV10 Heavy Chain EVQLLESGGG LVQPGGSLRL SCAASGFTFS NYAMNWVRQAPGKGLEWVSA ISGGGGSTYY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCAKES ITMVRGVMDY YGMDVWGQGT TVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSWTVPSS SLGTQTYICN VNHKPSNTKV DKRVEPKSCD KTHTCPPCPA PELLGGPSVF LFPPKPKDTL MISRTPEVTC VWDVSHEDP EVKFNWYVDG VEVHNAKTKP REEQYNSTYR VVSVLTVLHQ DWLNGKEYKC KVSNKALPAP IEKTISKAKG QPREPQVYTL PPSREEMTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSKLT VDKSRWQQGN VFSCSVMHEA LHNHYTQKSL SLSPG5 Light Chain DIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKPvariable region GKAPKLLIYA ASTLQGGVPS RFSGSGSGTE FTLTISSLQP(VL) EDFATYYCQH LNRFPRTFGQ GTKVEIK6 CDRL1 RASQGISSYL A7 CDRL2 AASTLQG8 CDRL3 QHLNRFPRT11 Light Chain DIQLTQSPSF LSASVGDRVT ITCRASQGIS SYLAWYQQKPGKAPKLLIYA ASTLQGGVPS RFSGSGSGTE FTLTISSLQP EDFATYYCQH LNRFPRTFGQ GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC12 CDRH1 NYAMNDBl / 163717029.3 93Docket No. 133186-5032-WO 13 CDRH2 AISGGGGSTY YADSVKG14 CDRH3 ESITMVRGVM DYYGMDVTable 2B. Anti-CDCPl sequences.SEQ ID SequenceAmino acid sequenceNO: identi fier15 Heavy Chain QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYAMSWVRQA PGQGLEWMGG variable region IIPILGTTNY AQKFQGRVTI TADKSTSTAY MELSSLRSED TAVYYCAREG (VH) LYAFDIWGQG TMVTVSS16 CDRH1 GGTFSSYAMS17 CDRH2 GIIPILGTTN YAQ18 CDRH3 AREGLYAFDI19 Light Chain DIQMTQSPSS LSASVGDRVT ITCRASQSIS SYLNWYQQKP GKAPKFLIYV variable region ASSLQSGVPS RFSGRGSGTD FTLTISSLQP EDFATYYCQQ SYSTPWTFGQ (VL) GTKVEIK20 CDRL1 RASQSISSYL N21 CDRL2 VASSLQS22 CDRL3 QQSYSTPWT

[0233] In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain (VH) that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 1, and / or a variable light chain (VL) that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment thereof comprises a variable heavy chain (VH) that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 1, and / or a variable light chain (VL) that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 5.DB1 / 163717029.3 94Docket No. 133186-5032-WO

[0234] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 1 and / or a VL comprising the amino acid sequence of SEQ ID NO: 5.

[0235] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 5.

[0236] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 5.

[0237] In some embodiments, the antibody or antigen binding fragment thereof comprises and / or consists of a VH that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least DBl / 163717029.3 95Docket No. 133186-5032-WOabout 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment thereof comprises and / or consists of a VH that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5.

[0238] In some embodiments, the antibody or antigen binding fragment thereof comprises and / or consists of a VH that comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a VL that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5.

[0239] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 15, and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15, and / or a VL that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19.

[0240] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and / or a VL comprising the amino acid sequence of SEQ ID NO: 19.

[0241] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence at least about 90%, at least aboutDBl / 163717029.3 96Docket No. 133186-5032-WO91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19.

[0242] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19.

[0243] In some embodiments, the antibody or antigen binding fragment thereof comprises and / or consists of a VH that comprises and / or consists of an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen binding fragment thereof comprises and / or consists of a VH that comprises and / or consists of an amino acidDBl / 163717029.3 97Docket No. 133186-5032-WOsequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 19.

[0244] In some embodiments, the antibody or antigen binding fragment thereof comprises and / or consists of a VH that comprises an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 15, and comprises a VL that comprises and / or consists of an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 19.

[0245] Any combination of a VH sequence and a VL sequence shown in Table 3 is also encompassed by the present disclosure.Table 3. Anti-CDCP 1 sequences.Ab SEQ VH SEQ VL Sourcename: ID NO ID NOhl2A04 23 QVTLRESGPALVKPTQTLTLT 250 DIVMTQSPLSLPVTPGEPA US20230050380A1 1- CTFSGFSLSTSGMGVSWIRQP SISCRSSQSIVHSSGNTYLVH1 / VL PGKALEWLAHI YWDDDKRYNP EWYLQKPGQSPQLLIYKVS SLKSRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARSGSYYG TLKISRVEAEDVGVYYCFQ SSLDSWGQGTTVTVSS GSHVPWTFGGGTKVEIKhl2A04 23 QVTLRESGPALVKPTQTLTLT 251 DIVMTQSPLSLPVTPGEPA US20230050380A1 1- CTFSGFSLSTSGMGVSWIRQP SISCRSSQSIVYSSGNTYLVH1 / VL PGKALEWLAHI YWDDDKRYNP EWYLQKPGQSPQLLIYKVSA SLKSRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARSGSYYG TLKISRVEAEDVGVYYCFQ SSLDSWGQGTTVTVSS GSHVPWTFGGGTKVEIKhl2A04 23 QVTLRESGPALVKPTQTLTLT 252 DIVMTQSPLSLPVTPGEPA US20230050380A1 1- CTFSGFSLSTSGMGVSWIRQP SISCRSSQNIVHSDGNTYLVH1 / VL PGKALEWLAHI YWDDDKRYNP EWYLQKPGQSPQLLIYKVSB SLKSRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARSGSYYG TLKISRVEAEDVGVYYCFQ SSLDSWGQGTTVTVSS GSHVPWTFGGGTKVEIKhl2A04 24 QVTLRESGPALVKPTQTLTLT 253 DIVMTQSPLSLPVTPGEPA US20230050380A1 1- CTFSGFSLSTFGMGVSWIRQP SISCRSSQSIVHSSGNTYLVH1A / V PGKALEWLAHI YWDDDKRYNP EWYLQKPGQSPQLLIYKVSL SLKSRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARSGSYYG TLKISRVEAEDVGVYYCFQ SSLDSWGQGTTVTVSS GSHVPWTFGGGTKVEIKhl4A04 25 QVQLVQSGAEVKKPGSSVKVS 254 EIVLTQSPATLSLSPGERA US20230050380A1 3VH1 / V CKASGFNIKDYYMNWVRQAPG TLSCSASSSVSYLYWYQQKLI QGLEWIGWIDPENANTI YDPK PGQAPRPWIYLTSNLASGV FQGRVTITADESTSTAYMEL S PARFSGSGSGTDFTLTISS SLRSEDTAVYYCYGSSYRFTY LEPEDFAVYYCQQWSSNPF WGQGTLVTVSS TFGGGTKVEIKhl4A04 25 QVQLVQSGAEVKKPGSSVKVS 255 EIVLTQSPATLSLSPGERA US20230050380A1 3VH1 / V CKASGFNIKDYYMNWVRQAPG TLSCSASSSVSYLYWYQQKL2 QGLEWIGWIDPENANTI YDPK PGQAPRPWIYLTSNLASGVFQGRVTITADESTSTAYMEL S PARFSGSGSGTDYTLTISS SLRSEDTAVYYCYGSSYRFTY LEPEDFAVYYCQQWSSNPF WGQGTLVTVSS TFGGGTKVEIKDBl / 163717029.3 98Docket No. 133186-5032-WOhl4A04 25 QVQLVQSGAEVKKPGSSVKVS 256 EIVLIQSPATLSLSPGERA US20230050380A1 3VH1 / V CKASGFNIKDYYMNWVRQAPG TLSCSASSSVSYLYWYQQKL3 QGLEWIGWIDPENANTI YDPK PGQAPRPWIYLTSNLASGVFQGRVTITADESTSTAYMEL S PARFSGSGSGTDFTLTISS SLRSEDTAVYYCYGSSYRFTY LEPEDFAVYYCQQWSSNPF WGQGTLVTVSS TFGGGTKVEIKhl4A04 26 QVQLVQSGAEVKKPGSSVKVS 257 EIVLIQSPATLSLSPGERA US20230050380A1 3VH2 / V CKASGFNIKDYYMNWVRQAPG TLSCSASSSVSYLYWYQQKL2 QGLEWIGWIDPENANTI YDPK PGQAPRPWIYLTSNLASGVFQGRATITADESTSTAYMELS PARFSGSGSGTDYTLTISS SLRSEDTAVYYCYGSSYRFTY LEPEDFAVYYCQQWSSNPF WGQGTLVTVSS TFGGGTKVEIKhl4A04 26 QVQLVQSGAEVKKPGSSVKVS 258 EIVLIQSPATLSLSPGERA US20230050380A1 3VH2 / V CKASGFNIKDYYMNWVRQAPG TLSCSASSSVSYLYWYQQKL3 QGLEWIGWIDPENANTI YDPK PGQAPRPWIYLTSNLASGVFQGRATITADESTSTAYMELS PARFSGSGSGTDFTLTISS SLRSEDTAVYYCYGSSYRFTY LEPEDFAVYYCQQWSSNPF WGQGTLVTVSS TFGGGTKVEIKhl4A06 27 EVQLVESGGGLVQPGGSLRLS 259 EIVLIQSPATLSLSPGERA US20230050380A1 3VH4 / V CAASGFTFSSYTMSWVRQAPE TLSCRASESVDSYGNSFMHLI KRLEWVAYISSGGGSTYYPDT WYQQKPGQAPRLLIFLASN VKGRFTISRDNAKNSLYLQMN LESGVPARFSGSGSRTDFT SLRAEDTAVYYCARYDLGFAY LTISSLEPEDFAVYYCQQN WGQGTLVTVSS NEDPWTFGGGTKVEIKhl4A06 27 EVQLVESGGGLVQPGGSLRLS 260 EIVLIQSPATLSLSPGERA US20230050380A1 3VH4 / V CAASGFTFSSYTMSWVRQAPE TLSCRASESVDSYGNSFMHL2 KRLEWVAYISSGGGSTYYPDT WYQQKPGQAPRLLIFLASNVKGRFTISRDNAKNSLYLQMN LESGVPARFSGSGSGTDFT SLRAEDTAVYYCARYDLGFAY LTISSLEPEDFAVYYCQQN WGQGTLVTVSS NEDPWTFGGGTKVEIKhl2A04 28 QVTLRESGPALVKPTQTLTLT US20230050380A1 1VH2 CTFSGFSLSTSGMGVSWIRQPPGKGLEWLAHIYWDDDKRYNP SLKSRLTISKDTSKNQWLTM TNMDPVDTATYYCARSGSYYG SSLDSWGQGTTVTVSShl2A04 29 QVTLRESGPALVKPTQTLTLT US20230050380A1 1VH2A CTFSGFSLSTFGMGVSWIRQPPGKGLEWLAHIYWDDDKRYNP SLKSRLTISKDTSKNQWLTM TNMDPVDTATYYCARSGSYYG SSLDSWGQGTTVTVSShl4A06 30 EVQLVESGGGLVQPGGSLRLS US20230050380A1 3VH2 CAASGFTFSSYTMSWVRQAPGKRLEWVAYISSGGGSTYYPDT VKGRFTISRDNAKNSLYLQMN SLRAEDTAVYYCARYDLGFAY WGQGTLVTVSShl4A06 31 EVQLQESGGGLVQPGGSLRLS US20230050380A1 3VH3 CAASGFTFSSYTMSWVRQAPGKRLEWVAYISSGGGSTYYPDT VKGRFTISRDNAKNSLYLQMN SLRAEDTAVYYCARYDLGFAY WGQGTLVTVSS CL03 32 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 Fab CAASGFNFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIKSDB1 / 163717029.3 99Docket No. 133186-5032-WO CL03 32 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFNFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADISKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK S CL03 33 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISSLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK S CL03 34 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 Fab CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGADYWGQGTLVTVS ITFGQGTKVEIK S CL03 35 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtoA HTWWVS YGIDYWGQGTLVTVS ITFGQGTKVEIK(" IgGl S01")CL03 36 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtol HTWWVS YGLDYWGQGTLVTVS ITFGQGTKVEIKS CL03 37 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtoL HTWWVS YGVDYWGQGTLVTVS ITFGQGTKVEIKS CL03 38 EVQLVESGGGLVQPGGSLRLS 262 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFNFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARTYWVQFW SLQPEDFATYYCQQSSSSLMtoV YGHFSYYRPALDYWGQGTLVT ITFGQGTKVEIKVSS CL07 38 EVQLVESGGGLVQPGGSLRLS 262 DIQMTQSPSSLSASVGDRV WO2022212876 Fab CAASGFNFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARTYWVQFW SLQPEDFATYYCQQSSSSL YGHFSYYRPALDYWGQGTLVT ITFGQGTKVEIK VSS CL07 39 EVQLVESGGGLVQPGGSLRLS 262 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARTYWVQFW SLQPEDFATYYCQQSSSSL YGHFSYYRPALDYWGQGTLVT ITFGQGTKVEIK VSSDB1 / 163717029.3 100Docket No. 133186-5032-WO CL07 33 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISSLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSSSSL HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgG3H7 40 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876 L CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQNHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGAOl 41 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS S L RAED TAVY YCARQ T H S Y Y S SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGA03 42 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS S L RAED TAVY YCARQ GH S Y Y S SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGA04 43 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS S L RAED TAVY YCARQAH S Y Y S SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGA05 44 EVQLVESGGGLVQPGGSLRLS 263 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS S L RAED TAVY YCARQ GQ S Y Y S SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGA06 33 EVQLVESGGGLVQPGGSLRLS 264 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGERP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGA08 33 EVQLVESGGGLVQPGGSLRLS 265 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGNVP HTWWVS YGMDYWGQGTLVTVS ATFGQGTKVEIK SIgGA09 33 EVQLVESGGGLVQPGGSLRLS 266 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGKRP HTWWVS YGMDYWGQGTLVTVS MTFGQGTKVEIKSDB1 / 163717029.3 101Docket No. 133186-5032-WO IgGAlO 45 EVQLVESGGGLVQPGGSLRLS 267 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQTGQRP HTWWVS YGMDYWGQGTLVTVS MTFGQGTKVEIK SIgGAll 33 EVQLVESGGGLVQPGGSLRLS 268 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSMQWP HTWWVS YGMDYWGQGTLVTVS KTFGQGTKVEIK SIgGBOl 46 EVQLVESGGGLVQPGGSLRLS 269 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS S L RAED TAVY YCARQ S H S F Y S SLQPEDFATYYCQQSLQRP HTWWVS YGMDYWGQGTLVTVS MTFGQGTKVEIK SIgGB03 45 EVQLVESGGGLVQPGGSLRLS 270 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQVELVP HTWWVS YGMDYWGQGTLVTVS MTFGQGTKVEIK SIgGB04 47 EVQLVESGGGLVQPGGSLRLS 271 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQDHSYYS SLQPEDFATYYCQQAGKRP HTWWVS YGMDYWGQGTLVTVS LTFGQGTKVEIK SIgGBOV 45 EVQLVESGGGLVQPGGSLRLS 272 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQSVDLT HTWWVS YGMDYWGQGTLVTVS ATFGQGTKVEIK SIgGB08 45 EVQLVESGGGLVQPGGSLRLS 273 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQLGVRA HTWWVS YGMDYWGQGTLVTVS ATFGQGTKVEIK SIgGCOl 33 EVQLVESGGGLVQPGGSLRLS 274 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGRKP HTWWVS YGMDYWGQGTLVTVS VTFGQGTKVEIK SIgGC03 45 EVQLVESGGGLVQPGGSLRLS 275 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQTAQSP HTWWVS YGMDYWGQGTLVTVS LTFGQGTKVEIKSDB1 / 163717029.3 102Docket No. 133186-5032-WO IgGC04 33 EVQLVESGGGLVQPGGSLRLS 276 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSRQRP HTWWVS YGMDYWGQGTLVTVS LTFGQGTKVEIK SIgGC05 33 EVQLVESGGGLVQPGGSLRLS 277 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGLMP HTWWVS YGMDYWGQGTLVTVS LTFGQGTKVEIK SIgGC06 33 EVQLVESGGGLVQPGGSLRLS 278 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGHRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgGC09 48 EVQLVESGGGLVQPGGSLRLS 279 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARKYHSYYS SLQPEDFATYYCQQSSQRP HTWWVS YGMDYWGQGTLVTVS ATFGQGTKVEIK SIgGD02 47 EVQLVESGGGLVQPGGSLRLS 280 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQDHSYYS SLQPEDFATYYCQQSGRQP HTWWVS YGMDYWGQGTLVTVS LTFGQGTKVEIK SIgGD03 45 EVQLVESGGGLVQPGGSLRLS 281 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQFMRPA HTWWVS YGMDYWGQGTLVTVS FTFGQGTKVEIK SIgGD04 45 EVQLVESGGGLVQPGGSLRLS 282 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARRSHSYYS SLQPEDFATYYCQQSGQPS HTWWVS YGMDYWGQGTLVTVS MTFGQGTKVEIK SIgGDOV 33 EVQLVESGGGLVQPGGSLRLS 283 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSVLRP HTWWVS YGMDYWGQGTLVTVS FTFGQGTKVEIK SIgGD08 49 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFNFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARIYWVDFW SLQPEDFATYYCQQSSSSL YGHFSYYRPALDYWGQGTLVT ITFGQGTKVEIK VSSDB1 / 163717029.3 103Docket No. 133186-5032-WOIgGD09 50 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAAS GFDAS S YS I HWVRQAP G TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgG87 51 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSAHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgG89 52 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgG94 53 EVQLVESGGGLVQPGGSLRLS 261 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTAWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK SIgG97 54 EVQLVESGGGLVQPGGSLRLS 284 DIQMTQSPSSLSASVGDRV WO2022212876CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASSYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS ITFGQGTKVEIK S CL03 55 EISEVQLVESGGGLVQPGGSL 285 MASDIQMTQSPSSLSASVG WO2022212876 Fab RLSCAASGFNFSSYSIHWVRQ DRVT I T CRAS Q S VS S AVAW APGKGLEWVASIYPYSGSTYY YQQKPGKAPKLLIYSASSL ADSVKGRFTISADTSKNTAYL YSGVPSRFSGSRSGTDFTL QMNSLRAEDTAVYYCARQSHS TISSLQPEDFATYYCQQSG Y Y S H T WWVS YGMD YWGQ GT L V QR P I T FGQ GT KVE I KRTVA TVSSASTKGPSVFPLAPSSKS APSVFIFPPSDSQLKSGTA TSGGTAALGCLVKDYFPEPVT SVVCLLNNFYPREAKVQWK VSWNSGALTSGVHTFPAVLQS VDNALQS GNS QE SVTEQDS SGLYSLSSWTVPSSSLGTQT KDSTYSLSSTLTLSKADYE YI CNVNHKPSNTKVDKKVEPK KHKVYACEVTHQGLSSPVT SC KSFNRGEC CL03 56 EVQLVESGGGLVQPGGSLRLS 286 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFNFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS I T FGQ GT KVE I KRTVAAPS SASTKGPSVFPLAPSSKSTSG VFIFPPSDSQLKSGTASW GTAALGCLVKDYFPEPVTVSW CLLNNFYPREAKVQWKVDN NSGALTSGVHTFPAVLQSSGL ALQSGNSQESVTEQDSKDS YS LS SWTVPS SS LGTQTYI C TYSLSSTLTLSKADYEKHK NVNHKPSNTKVDKKVEPKSCD VYACEVTHQGLS S PVTKS F KTHTCPPCPAPELLGGPSVFL NRGEC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEALHNHYTQKSLS LS PGKDB1 / 163717029.3 104Docket No. 133186-5032-WOCL03 57 EVQLVESGGGLVQPGGSLRLS 287 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADISKNTAYLQMN VPSRFSGSRSGTDFTLTISSLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRP HTWWVS YGMDYWGQGTLVTVS 11 FGQ GT KVE I KRTVAAPS SASTKGPSVFPLAPSSKSTSG VFIFPPSDSQLKSGTASW GTAALGCLVKDYFPEPVTVSW CLLNNFYPREAKVQWKVDN NSGALTSGVHTFPAVLQSSGL ALQSGNSQESVTEQDSKDS YS LS SWTVPS SS LGTQTYI C TYSLSSTLTLSKADYEKHK NVNHKPSNTKVDKKVEPKSCD VYACEVTHQGLS S PVTKS F KTHTCPPCPAPELLGGPSVFL NRGEC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGK CL03 58 EVQLVESGGGLVQPGGSLRLS 288 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtoA HTWWVS YGADYWGQGTLVTVS I T FGQ GT KVE I KRTVAAPS(" IgGl SASTKGPSVFPLAPSSKSTSG VFIFPPSDSQLKSGTASW01") GTAALGCLVKDYFPEPVTVSW CLLNNFYPREAKVQWKVDN NSGALTSGVHTFPAVLQSSGL ALQSGNSQESVTEQDSKDS YS LS SWTVPS SS LGTQTYI C TYSLSSTLTLSKADYEKHK NVNHKPSNTKVDKKVEPKSCD VYACEVTHQGLS S PVTKS F KTHTCPPCPAPELLGGPSVFL NRGEC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGK CL03 59 EVQLVESGGGLVQPGGSLRLS 289 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtol HTWWVS YGIDYWGQGTLVTVS I T FGQ GT KVE I KRTVAAPS SASTKGPSVFPLAPSSKSTSG VFIFPPSDSQLKSGTASW GTAALGCLVKDYFPEPVTVSW CLLNNFYPREAKVQWKVDN NSGALTSGVHTFPAVLQSSGL ALQSGNSQESVTEQDSKDS YS LS SWTVPS SS LGTQTYI C TYSLSSTLTLSKADYEKHK NVNHKPSNTKVDKKVEPKSCD VYACEVTHQGLS S PVTKS F KTHTCPPCPAPELLGGPSVFL NRGEC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 105Docket No. 133186-5032-WOCL03 60 EVQLVESGGGLVQPGGSLRLS 290 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtoL HTWWVS YGLDYWGQGTLVTVS 11 FGQ GT KVE I KRTVAAPS SASTKGPSVFPLAPSSKSTSG VFIFPPSDSQLKSGTASW GTAALGCLVKDYFPEPVTVSW CLLNNFYPREAKVQWKVDN NSGALTSGVHTFPAVLQSSGL ALQSGNSQESVTEQDSKDS YS LS SWTVPS SS LGTQTYI C TYSLSSTLTLSKADYEKHK NVNHKPSNTKVDKKVEPKSCD VYACEVTHQGLS S PVTKS F KTHTCPPCPAPELLGGPSVFL NRGEC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGK CL03 61 EVQLVESGGGLVQPGGSLRLS 291 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSYSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTYYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISH3- SLRAEDTAVYYCARQSHSYYS SLQPEDFATYYCQQSGQRPMtoV HTWWVS YGVDYWGQGTLVTVS I T FGQ GT KVE I KRTVAAPS SASTKGPSVFPLAPSSKSTSG VFIFPPSDSQLKSGTASW GTAALGCLVKDYFPEPVTVSW CLLNNFYPREAKVQWKVDN NSGALTSGVHTFPAVLQSSGL ALQSGNSQESVTEQDSKDS YS LS SWTVPS SS LGTQTYI C TYSLSSTLTLSKADYEKHK NVNHKPSNTKVDKKVEPKSCD VYACEVTHQGLS S PVTKS F KTHTCPPCPAPELLGGPSVFL NRGEC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGK CL07 62 EISEVQLVESGGGLVQPGGSL 292 MASDIQMTQSPSSLSASVG WO2022212876 Fab RLSCAASGFNFSSSSIHWVRQ DRVT I T CRAS Q S VS S AVAW APGKGLEWVASIYPYSGSTSY YQQKPGKAPKLLIYSASSL ADSVKGRFTISADTSKNTAYL YSGVPSRFSGSRSGTDFTL QMNSLRAEDTAVYYCARTYWV TISSLQPEDFATYYCQQSS QFWYGHFSYYRPALDYWGQGT S S L I T FGQ GT KVE I KRTVA LVTVS SAS TKGPSVFPLAPS S APSVFIFPPSDSQLKSGTA KSTSGGTAALGCLVKDYFPEP SVVCLLNNFYPREAKVQWK VTVSWNSGALTSGVHTFPAVL VDNALQS GNS QE SVTEQDS QSSGLYSLSSWTVPSSSLGT KDSTYSLSSTLTLSKADYE QTYI CNVNHKPSNTKVDKKVE KHKVYACEVTHQGLSSPVTPKSC KSFNRGECDB1 / 163717029.3 106Docket No. 133186-5032-WOCL07 63 EVQLVESGGGLVQPGGSLRLS 293 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFNFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQ KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADISKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARTYWVQFW SLQPEDFATYYCQQSSSSL YGHFSYYRPALDYWGQGTLVT I T FGQ GT KVE I KRTVAAPS VS SASTKGPSVFPLAPS SKS T VFIFPPSDSQLKSGTASW SGGTAALGCLVKDYFPEPVTV CLLNNFYPREAKVQWKVDN SWNS GALTSGVHTFPAVLQS S ALQSGNSQESVTEQDSKDS GLYS LS SWTVPS SS LGTQTY TYSLSSTLTLSKADYEKHK I CNVNHKPSNTKVDKKVEPKS VYACEVTHQGLS S PVTKS F CDKTHTCPPCPAPELLGGPSV NRGEC FLFPPKPKDTLMI SRTPEVTC WVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTI SKAKGQPRE PQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMH EALHNHYTQKS LS LS PGK CL07 64 EVQLVESGGGLVQPGGSLRLS 294 DIQMTQSPSSLSASVGDRV WO2022212876 IgG CAASGFDFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQHl- KGLEWVASIYPYSGSTSYADS KPGKAPKLLIYSASSLYSGNtoD VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTISSLRAEDTAVYYCARTYWVQFW SLQPEDFATYYCQQSSSSL YGHFSYYRPALDYWGQGTLVT I T FGQ GT KVE I KRTVAAPS VS SASTKGPSVFPLAPS SKS T VFIFPPSDSQLKSGTASW SGGTAALGCLVKDYFPEPVTV CLLNNFYPREAKVQWKVDN SWNS GALTSGVHTFPAVLQS S ALQSGNSQESVTEQDSKDS GLYS LS SWTVPS SS LGTQTY TYSLSSTLTLSKADYEKHK I CNVNHKPSNTKVDKKVEPKS VYACEVTHQGLS S PVTKS F CDKTHTCPPCPAPELLGGPSV NRGEC FLFPPKPKDTLMI SRTPEVTC WVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTI SKAKGQPRE PQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMH EALHNHYTQKS LS LS PGKIgG3H7 65 EVQLVESGGGLVQPGGSLRLS 295 MTQSPSSLSASVGDRVTIT WO2022212876 L CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSSSSLITF HTWWVS YGMDYWGQGTLVTVS GQ GT KVE I KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 107Docket No. 133186-5032-WOIgGAOl 66 EVQLVESGGGLVQPGGSLRLS 296 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQNHSYYS PEDFATYYCQQSGQRPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGA03 67 EVQLVESGGGLVQPGGSLRLS 297 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ S L RAED TAVY YCARQ T H S Y Y S PEDFATYYCQQSGQRPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGA04 68 EVQLVESGGGLVQPGGSLRLS 298 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ S L RAED TAVY YCARQ GH S Y Y S PEDFATYYCQQSGQRPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 108Docket No. 133186-5032-WOIgGA05 69 EVQLVESGGGLVQPGGSLRLS 299 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ S L RAED TAVY YCARQAH S Y Y S PEDFATYYCQQSGQRPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGA06 70 EVQLVESGGGLVQPGGSLRLS 300 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ S L RAED TAVY YCARQ GQ S Y Y S PEDFATYYCQQSGQRPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGA08 71 EVQLVESGGGLVQPGGSLRLS 301 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSGERPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 109Docket No. 133186-5032-WOIgGA09 72 EVQLVESGGGLVQPGGSLRLS 302 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSGNVPATF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGAlO 73 EVQLVESGGGLVQPGGSLRLS 303 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSGKRPMTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGAll 74 EVQLVESGGGLVQPGGSLRLS 304 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQTGQRPMTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 110Docket No. 133186-5032-WOIgGBOl 75 EVQLVESGGGLVQPGGSLRLS 305 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSMQWPKTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGB03 76 EVQLVESGGGLVQPGGSLRLS 306 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ S L RAED TAVY YCARQ S H S F Y S PEDFATYYCQQSLQRPMTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGB04 77 EVQLVESGGGLVQPGGSLRLS 307 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQVELVPMTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 111Docket No. 133186-5032-WOIgGB07 78 EVQLVESGGGLVQPGGSLRLS 308 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQDHSYYS PEDFATYYCQQAGKRPLTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGB08 79 EVQLVESGGGLVQPGGSLRLS 309 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQSVDLTATF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGCOl 80 EVQLVESGGGLVQPGGSLRLS 310 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQLGVRAATF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 112Docket No. 133186-5032-WOIgGC03 81 EVQLVESGGGLVQPGGSLRLS 311 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSGRKPVTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGC04 82 EVQLVESGGGLVQPGGSLRLS 312 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQTAQSPLTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGC05 83 EVQLVESGGGLVQPGGSLRLS 313 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSRQRPLTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 113Docket No. 133186-5032-WOIgGC06 84 EVQLVESGGGLVQPGGSLRLS 314 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSGLMPLTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGC09 85 EVQLVESGGGLVQPGGSLRLS 315 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSGHRPITF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGD02 86 EVQLVESGGGLVQPGGSLRLS 316 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARKYHSYYS PEDFATYYCQQSSQRPATF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 114Docket No. 133186-5032-WOIgGD03 87 EVQLVESGGGLVQPGGSLRLS 317 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQDHSYYS PEDFATYYCQQSGRQPLTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGD04 88 EVQLVESGGGLVQPGGSLRLS 318 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQFMRPAFTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGDOV 89 EVQLVESGGGLVQPGGSLRLS 319 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARRSHSYYS PEDFATYYCQQSGQPSMTF HTWWVS YGMDYWGQGTLVTVS GQGTKVEI KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VD VS HED PEVK FNWY VD GVE V HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKDB1 / 163717029.3 115Docket No. 133186-5032-WOIgGD08 90 EVQLVESGGGLVQPGGSLRLS 320 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFDFSSYSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTYYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARQSHSYYS PEDFATYYCQQSVLRPFTF HTWWVS YGMDYWGQGTLVTVS GQGT KVE I KRTVAAPSVFI SASTKGPSVFPLAPSSKSTSG FPPSDSQLKSGTASWCLL GTAALGCLVKDYFPEPVTVSW NNFYPREAKVQWKVDNALQ NSGALTSGVHTFPAVLQSSGL SGNSQESVTEQDSKDSTYS YS LS SWTVPS SS LGTQTYI C LSSTLTLSKADYEKHKVYA NVNHKPSNTKVDKKVEPKSCD CEVTHQGLSSPVTKSFNRG KTHTCPPCPAPELLGGPSVFL EC FPPKPKDTLMI SRTPEVTCW VDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFS C SVMHEA LHNHYTQKSLS LS PGKIgGD09 91 EVQLVESGGGLVQPGGSLRLS 321 MTQSPSSLSASVGDRVTIT WO2022212876CAASGFNFSSSSIHWVRQAPG CRASQSVS SAVAWYQQKPG KGLEWVASIYPYSGSTSYADS KAPKLLIYSASSLYSGVPS VKGRFTISADTSKNTAYLQMN RFSGSRSGTDFTLTISSLQ SLRAEDTAVYYCARI YWVDFW PEDFATYYCQQSSSSLITF YGHFSYYRPALDYWGQGTLVT GQGTKVEI KRTVAAPSVFI VS SASTKGPSVFPLAPS SKS T FPPSDSQLKSGTASWCLL SGGTAALGCLVKDYFPEPVTV NNFYPREAKVQWKVDNALQ SWNS GALTSGVHTFPAVLQS S SGNSQESVTEQDSKDSTYS GLYS LS SWTVPS SS LGTQTY LSSTLTLSKADYEKHKVYA I CNVNHKPSNTKVDKKVEPKS CEVTHQGLSSPVTKSFNRG CDKTHTCPPCPAPELLGGPSV E FLFPPKPKDTLMI SRTPEVTC WVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTI SKAKGQPRE PQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMH EALHNHYTQKS LS LS PGK10D7 92 EVQLQQFGAELVKPGASVKIS 322 NIVMTQSPQSMSMSVGERV US20220389113A1 CKASGYSFSDFNIEWLKQSHG TLSCKASENVGAYVSWFQQ KSLEWIGDINPNYDSTNYNQK KPDQSPKLLILAASNRYTG FKGRATLTVDKSSSTAYMEVR VPARFIGSGSATDFTLTIS SLTSEDTAVYYCARLGYGYAM SVQAEDLADYHCGQSYTYP DYWGQGTSVTVSS YTFGGGTKLEIKRADAAPTVSDB1 / 163717029.3 116Docket No. 133186-5032-WOChimer 93 EVQLQQFGAELVKPGASVKIS 323 IVMTQSPQSMSMSVGERVT US20220389113A2 ic CKASGYSFSDFNIEWLKQSHG LSCKASENVGAYVSWFQQK10D7 KSLEWIGDINPNYDSTNYNQK PDQSPKLLILAASNRYTGVFKGRATLTVDKSSSTAYMEVR PARFIGSGSATDFTLTISS SLTSEDTAVYYCARLGYGYAM VQAEDLADYHCGQS YTYPY DYWGQGTSVTVSSASTKGPSV TFGGGTKLEIKRADAAPTV FPLAPS SKSTS GGTAALGCLV S I FPPSDEQLKS GTASWC KDYFPEPVTVSWNSGALTSGV LLNNFYPREAKVQWKVDNA HTFPAVLQSSGLYSLSSWTV LQSGNSQESVTEQDSKDST PS SS LGTQTYI CNVNHKPSNT YS LSS TLTLSKADYEKHKV KVDKKVEPKSCDKTHTCPPCP YACEVTHQGLSS PVTKS FN APELLGGPSVFLFPPKPKDTL RGEC MI SRTPEVTCVVVDVSHEDPE VKFNWYVD GVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKT I SKAKGQPREPQVYTLPPSRE EMTKNQVS LTC LVKGFY PSD I AVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQ GNVFS C SVMHEALHNHY TQKS LSLSPGKMab 94 QVTLKESGPGILQPSQTLSLT 324 DVLMTQTPLSLPVSLGDQA US20110070246A1 CDCP1- CSFSGFSLSTAGVGVSWIRQP SISCRSSQNIVHSYGNTYL004 SGKGLEWLAHI YWDDDKRYNP EWYLQKPGQSPKLLIYKVS SLKSRLTISKDTSRNQVFLKI NRFSGVPDRFSGSGSGTDF TSVDSADTATYFCSRSTSVEE T L KI S RVEAE DL GV Y YC FQ AFDVWGAGTTVTVSS GSHVPWTFGGGTKLEIKMab 95 QVTLKESGPGILQSSQTLSLT 325 DWMTQTPLTLSVTIGQPA US20110070246A1 CDCP1- CSFSGFSLSTAGMGVSWIRQP SISCKSSQSLLYTNGKTYL012 SGKGLEWLAHI YWDDDKRYNP IWLLQRPGQS PKRLI YLVS SLKSRLTVSKGTSRNQVLLKI KLDSGVPDRFSGSGSGTDF TSVDAADTATYYCARSDSFGD TLKISRVEAEDLGVYYCLQ FDYWGQGTTLTVSS STHFPYTFGGGTKLEIKMab 96 QVHLKQSGPGLVQPSQSLSIT 326 DWLTQTPLSLPVIIGDQA US20110070246A1 CDCP1- CTVSGFSLTNFGLHWVRQSPG SISCKSTKSLLNSAGFTYL015 KGLEWLGVIWSGGVTDYNAAF GWYLQKPGQSPQLLIYLVS ISRLSISKDNSKSQVFFKMNS NRFSGVPDRFSGSGSGTDF LQPNDTAI YYCARNYDHDYSM TLKISRVEAEDLGVYFCFQ DYWGQGISVSVSS SSYLPLTFGSGTKLEIK CP13E1 97 EVQLVQSGAEVKKPGASVKVS 327 EIVLTQSPATLSLSPGERA US20220119545A1 0 CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ QGLEWMGIINPSGGSTSYAQK RPGQAPRLLIYDASNRATG FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDGVLRYF SLEPEDFAVYYCQQRANVF DWLLDYYYYMDVWGKGTTVTV TFGQGTKVEIK SS CP13E1 98 EVQLVQSGAEVKKPGASVKVS 328 EIVLTQSPATLSLSPGERA US20220119545A1 0- CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ54HC- QGLEWMGIINPSGGSTSYAQK RPGQAPRLLIYDASNRATG89LC FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDGELRHF SLEPEDFAVYYCQQRAQEF DHLLDYHYYMDVWGQGTTVTV TFGQGTKVEIK SS CP13E1 99 EVQLVQSGAEVKKPGASVKVS 329 EIVMTQSPATLSLSPGERA US20220119545A1 0- CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ54HC- QGLEWMGIINPSGGSTSYAQK KPGQAPRLLIYDASNRATG89LCvl FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDGELRHF SLQPEDFAVYYCQQRAQEF DHLLDYHYYMDVWGQGTTVTV TFGQGTKVEIK SS CP13E1 100 EVQLVQSGAEVKKPGASVKVS 330 EIVMTQSPATLSLSPGERA US20220119545A1 0- CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ54HCvl QGLEWMGIINPSGGSTSYAQK KPGQAPRLLIYDASNRATG3- FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS89LC1 SLRSEDTAVYYCARDAELRHF SLQPEDFAVYYCQQRAQEFTFGQGTKVEIKDB1 / 163717029.3 117Docket No. 133186-5032-WODHLLDYHYYMDVWGQGTTVTVS3CP13E1 101 EVQLVQSGAEVKKPGASVKVS 331 EIVLTQSPATLSLSPGERA US20220119545A1 0-291 CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ QGLEWMGIINPSGGSTSYAQK RPGQAPRLLIYDASNRATG FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDGELRHF SLEPEDFAVYYCQQRANVF DQVYNYHYYMDVWGQGTTVTV TFGQGTKVEIK SSAntibo 102 EIVLTQSPATLSLSPGERATL 332 EIVLTQSPATLSLSPGERA US20220119545A1 dy 23 SCRASQSVGSYLAWYQQRPGQ TLSCRASQSVGSYLAWYQQAPRLLI YDASNRATGI PARES RPGQAPRLLIYDASNRATG GSGSGTDFTLTISSLEPEDFA IPARFSGSGSGTDFTLTIS VYYCQQRANVFTFGQGTKVEI SLEPEDFAVYYCQQRANVF K TFGQGTKVEIKAntibo 103 QVQLVE 3 GGGWQ PGRS LRL 3 333 EIVMTQSPDTLSLSPGERA US20220119545A1 dy 24 CAASGFTFSSYGMHWVRQAPG TLSCRASQKI YYSYLAWYQ KGLEWVAVISYDGSNKYYADS QKPGQAPRLLISGASTRAS VKGRFTISRDNSKNTLYLQMN DISDRFSGGGSGTDFTLTI S L RAED TAVY YCARGVGL P D I NSLESEDAAVYYCQQYDSL WGQGTMVTVSS PVTFGRGTKLEIKAntibo 104 QVQLVQSGAEVKKPGSSVKVS 334 SYELTQPPSVSVSPGQTAR US20220119545A1 dy 76 CKAS GGT FS S YAI S WVRQAP G ITCSGDALPKKYAFWYQQKQGLEWMGGI I P I FGTAN YAQK SGQAPVLVIYEDSKRPSGI FQ GRVT I T ADK S T S T AYMEL S PEKFSGSSSGTMATLTISG SLRSEDTAVYYCARDPTYFDW AQVEDEADYYCYSTDSSDN TRRGYYYMDVWGKGTTVTVS S PRGVFGGGTKLTVL14H4 105 EVQLLESGGDLVQPGGSLRLS 335 DIQMTQSPSSLSASVGDRV U320200181281 VH CAAS GET FNS YAMS WVRQAP G TITCRASQGISIYLAWFQQ Al KGLEWVSVLSGSGGDIHYADS KPGKVPKLLI YAASTLQSG VKGRFT VS RDN 3 KNML YLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYFCAQQWPQGYW SLQPEDVATYYCQKYNSAP GQGTLVTVSS FTFGPGTKVEIK03B05 106 QVQLVE 3 GGGWQ PGRS LRL 3 336 EIVMTQSPATLSVSPGERA U320200181281 VH CAASGFTFSSYGMHWVRQAPG TLSCRASQSVSSNLAWYQQ Al KGLEWVAIIWYDGSNKYYADS KP GQAP RL L I YGAS T RAT G VKGRFT 13 RDN 3 KNT LYLQMN IPARFSGSGSGTEFTLTIS3 LRAEDTAVYYCAKD P 3 YS 3 G SLQSEDFAVYYCQQYNNWP YYLFDFWGQGTLVTVSS LTFGGGTKVEIK03C05 107 EVQVLE S GGGLVQ PGGS LRL S 337 DIQMTQSPSSLSASVGDRV U320200181281CAAS GET FS S YVMS WVRQAP G TITCRASQDISIYLAWFQQ Al KGLEWVSGISGSGGSTHYADS KPGKVPKVLI YAASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGTGTDFTLTIS SLRAEDTALYYCAQQWPQGYW SLQPEDVATYFCQKYNSAP GQGTLVTVSS FTFGPGTKLEIK27H10 108 QVQLVQSGAEVKKPGSSVKVS 338 DIQMTQSPSSLSASVGDRV U320200181281CKASGGTFSSYAMSWVRQAPG T I T CRAS Q S I S S YLNWYQQ Al QGLEWMGGIIPILGTTNYAQK KPGKAPKFLIYVASSLQSG FQ GRVT I T ADK 3 T 3 T AYMEL 3 VPSRFSGRGSGTDFTLTIS SLRSEDTAVYYCAREGLYAFD SLQPEDFATYYCQQSYSTP IWGQGTMVTVSS WTFGQGTKVEIK03B11 109 QVQLQQWDAGLLKPSETLSLT 339 DIQLTQSPSFLSASVGDRV U320200181281CAVYGGSFSSYYWSWIRQPPG TIT CRAS QGI S S YLAWYQQ Al KGLEWIGEINHSGSTSYNPSL KPGKAPKLLI YAASTLQSG KSRVTISIDTSKNQFSLKLNS VPSRFSGSGSGTEFTLTIS MTAADTAVYFCAAS P YFDYWG SLQPEDFATYYCQQLNSYP QGTLVTVSS RTFGQGTKVEIK04G06 110 QVQLVE 3 GGGWQ PGRS LRL 3 340 DIQLTQSPSFLSASVGDRV U320200181281CWSGFTLSSYGMHWVRQAPG TITCRASQDISNYLAWYQQ Al KGLEWVAVIWYDGSDKYYADS KPGKAPKLLI SASTLQSGV VKGRFT 13 RDN 3 KNT LYLQMN PSRFSGSGSGTEFILTISS SLRAEDTAVYYCARDDWGFDY LQPEDFATYYCQHLNSYPF WGQGTLVTVSS GQGTKVEIK42C5 111 EVQLVE 3 GGGLVQ PGGS LRL S 341 DIVMTQSPLSLPVTPGEPA U320200181281CAAS GET FS RYWMNWVRQAP G SISCRSSRSLLHSSGYNFL Al KGLEWVANIKQDGSEKDYVDS DWFLQKPGQSPQLLIFLGSVKGR FT 13 RDNAKN 3 L FLQM 3 DRASGVPDRFSGSGSGTDFDB1 / 163717029.3 118Docket No. 133186-5032-WOS L RAED TAVY YCARVMY S S GW T LK I S RVE T E DVGV Y YCMQ SFDYWGQGTLVTVSS ALQTPITFGQGTRLEIK47G7 112 EVQLVESGGGLVQPGGSLRLS 342 DIVMTQSPLSLPVTPGEPA US20200181281CAAS GFT FS S YWMS WVRQAP G SISCRSSQSLLHSSGHNFL Al KGLEWVANIKQDGSEKDYVDS DWYLQKPGQSPQLLIYLGS VKGRFTISRDNAKNSLYLQMN NRASGVPDRFSGSGSGTDF S L RVED TAVY YCARE GG S S GW T LK I S RVEAE DVGV Y YCMQ TFDYWGQGTLVTVSS ALQTPPTFGQGTKLEIK18C06 113 QVQLQESGPGQVKPSETLSLT 343 EIVMTQSPATLSVSPGERA US20200181281CTVSGGSISSSFWSWIRQPPG TLSCRASQSVSSNLAWYQQ Al KGLEWIGYIYYSESTNYNPSL KPGQAPRLLIYGASTRATG KRRVTLSVDTSKNQFSLKLTS IPARFSGSGSGTEFTLTIS VTTADTAVYYCARNIGVAGLF SLQSEDFAVYYCQQYNNWP DYWGQGTLVTVSS LTFGGGTKVEIK11F9 114 QVQLQESGPGLVKPSETLSLT 344 EIVMTQSPATLSVSPGERA US20200181281CTVSGGSISSYYWSWIRQPPG TLSCRASQSVSSNLAWYQQ Al KGLEWIGYIYYSGSTNYNPSL KPGQAPRLLIYGASTRATG KSRVTISVDTSKNQFSLKLSS IPARFSGSGSGTEFTLTIS VT AADT AV Y YCARN I GVAGL F SLQSEDFAVYYCQQYNNWP DYWGQGTLVTVSS LTFGGGTKLEIK10E2. 115 QVQLVE S GGGWQ PGRS LRL S 345 DIQMTQSPSTLSASVGDRV US20200181281CAASGFTFSSYGMHWVRQAPG TIT CRAS Q S I S T WLAWYQQ Al KGLEWVAWWYDGTIKYYADS KPGKAPKFLIYKASSLESG VKGRFTISRDNPKNTLYLQMN VPSRFSGSGSGTEFTLTIS SLRAEDTAVYYCASQYSSGWH SLQPDDFATYYCQQYSGYS TDFFDVWGQGTMVTVSS LTFGGGTKVEIK01E2. 116 QVQLVE S GGGWQ PGRS LRL S 346 EIVLTQSPATLSLSPGERA US20200181281CAASGFTFSSYGMHWVRQAPG TLSCRASQTVPNYLAWYQQ Al KGLEWVAVIWYAGSNKYYADS KPGQAPRLLIYDASNRATD VKGRFTISRDNSKNTLYLQMN IPARFSGSGSGTDFTLTIS SLRAEDTAVYYCAGWDFDYWG SLEPEDFAVYYCQQRANWP QGTLVTVSS PITFGQGTRLEIK41A9 117 QVQLQQWGAGLLKPSETLSLT 347 EIVLTQSPATLSLSPGERA US20200181281CAVYGGSFSDYYWSWIRQPPG TLSCRASQSVRRYLAWYQQ Al KGLEWIGEINHSGSTNYNPSL KPGQAPRLLIYDASNRATG KSRVTISVDTSKNQFSLKLSS IPARFSGSGSGTDFTLTIS VTAADTAVYYCARDYDVLTGH SLEPEDFAVYYCQQRNNWP FYYYYGMDVWGQGTTVTVS S LTFGGGTKLEIK02F3 118 QVQLVE S GGGWQ PGRS LRL S 348 DIVMTQSPLSLPVTPGEPA US20200181281CAASGFSFSDYGIHWVRQAPG SISCRSSQSLLHSNGYNYL Al KGLEWVAVIWYDGSNKYYADS DWYLQKPGQSPQILIYLGS VKGRFT I S RDN S KNT L YLQVN NRASGVPDRFSGSGSGTDF S L IAEDTAVYYCARDRG YS S G T LK I S RVEAE DVGV Y YCMQ WYVDYYYYGMDVWGQGTTVTV ALQTPWTFGQGTKLEIK SS50D6 119 EVQVLE S GGGLVQ PGGS LRL S 349 DIQLTQSPSFLSASVGDRV US20200181281CAASGFTFSNYAMNWVRQAPG TITCRASQGISNYLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKVPKLLI YAVSTLQSG VKGRAT I S RDN S ENT LYLQMN VPSRFSGSGSGTEFTLTIS S LRAEDTAVYYCAKT S S GWYD SLQPEDFATYYCQQLNSYP SYYDYYGLDVWGQGTTVTVSS FTFGGGTKLEIK38E11. 120 EVQLLESGGGLVQPGGSLRLS 350 DIQLTQSPSFLSASVGDRV US20200181281CAASGFTFSNYAMNWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S L RAED TAVY YCAKE S I TMVR SLQPEDFATYYCQHLNRFP GVMDYYGMDVWGQGTTVTVSS RTFGQGTKVEIK05A8 121 EVQLLESGGGLVQPGGSLRLS 351 EIVMTQSPATLSVSPGERA US20200181281CAASGFTFSNYAMSWVRQAPG TLSCRASQSVSSNLAWYQQ Al KGLEWVSAISGRGGSTYYADS KPGQAPRLLIYGASTRATG VKGRFTISRDNSKNTLYLQMN IPARFSGSGSGTEFTLTFS SLRAEDTAVYYCAKDIVWPA SLQSEDFWYYCQQYNNWP AKGYVMDAWGQGASVTVSS LTFGQGTRLEIKDB1 / 163717029.3 119Docket No. 133186-5032-WO12C2 122 QEQLVESGGGWQPGRSLRLS 352 DILMTQSPSSLSASVGDRV US20200181281CVTSGFTFSSYGMHWVRQAPG TITCRASQGINYYLAWYQQ Al KGLEWVAVIWYDGTNKYYADT KPGKVPKLLI YTASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTGVYYCAREGCDTIS SLQPEDVATYFCQKYNSAP CPYYYYGMDVWGQGTTITVSS FTFGPGTKLEIK03G11 123 EVQLLESGGGLVQPGGSLRLS 353 EIVMTQSPATLSVSPGERG US20200181281CAASGFTFSSYAMSWVRQAPG TLSCRASQSVSSNLAWYQQ Al KGLEWVSAISGSGNSAYYADS KPGQAPRLLIYGASIRATG VKGRFT I S RDN S KNT LFLQMN IPARFSGSGSGTEFILTIN SLRADDTAVYYCASSSGWYLV SLQSEDFAVYYCQQYNNWP YYFDLWGRGTLVTVS S LTVGGGTKVEIK06H1 124 EVQLLESGGGLVQPGGSLRLS 354 DIQMTQSPSSLSASVGDRV US20200181281CAASGFTFSSYAMSWVRQAPG TITCRASQGISIYLAWFQQ Al KGLEWVSGISGSGGNTHYADS KPGKVPKLLI YAASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTALYYCAQQWPQGYW SLQPEDFATYYCQKYNSAP GQGTLVTVSS FTFGPGTKLEIK07C06- 125 EVQLLESGGGLVQPGGSLGLS 355 DIQMTQSPSSLSASVGDRV US20200181281 D2 CAASGFTFSNYIMSWVRQAPG TITCRASQGITI YLAWFQQ Al KGLEWVSGISGSGGSTHYAGS KPGKVPKLLI YAASTLQSG VKGRFT I S RDN S KNT LNLQMN VPSRFSGSGSGTDFTLTIS SLRVEDTAVYHCVQQWPQGYW SLQPEDVATYYCQKYNSAP GQGTLVTVSS FTFGPGTKLEIK09F6 126 EVQLLESGGGLVQPGGSLRLS 356 DIQMTQSPSSLSASVGDRV US20200181281CAAS GFT FS S YAMS WVR LAP G TITCRASQGISIYLAWFQQ Al KGLEWVSGLSGSGGDTHYAGS KPGKVPKLLI YAASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTALYYCAQQWPQGYW SLQPEDVATYYCQKYNSAP GQGTLVTVSS FTFGPGTKLEIK14D4 127 EVQLLESGGGLVQPGESLRLS 357 DIQMTQSPSSLSASVGDRV US20200181281CAASGFTFSSYAMSWVRQAPG TITCRASQDI SI YLAWFQQ Al KGLEWVSGISGSGGSTHYADS RPGKVPKLLI YAASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAAYYCAQQWPQGHW SLQPEDVATYYCQKYNSDP GQGTLVTVSS FTFGPGTKVEIK15H5 128 EVQLLESGGGLVQPGGSLRLS 358 DIQMTQSPSSLSASVGDRV US20200181281CAASGFTFSSYAMSWVRQAPG TITCRASQDI SI YLAWFHQ Al KGLEWVSVLSGSGDDTHYADS KPGKVPKLLI YAASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCAHQWPQGYW SLQPEDVAAYYCQKYNSAP GQGTLVTVSS FTFGPGTKLEIK20F5 129 EVQLLESGGGLVQPGGSLRLS 359 DIQMTQSPSSLSATVGDRV US20200181281CAASGFTFSSYVMSWVRQTPG TITCRASQGISIYLAWFQQ Al KGLEWVSGISGSGGSTHYTDS KPGKVPKNLI YAASTLQSG VQGRFT I S RDN S KNT LYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCVQQWPQGYW SLQPEDFATYYCQKYNSAP GQGTLVTVSS FTFGPGTKLEIK38A6 130 EVQVLESGGGLVQPGESLRLS 360 DIQMTQSPSSLSASVGDRV US20200181281CAASGFTFNTYAMSWVRQAPG TIT CRAS QGI S I YLAWYHQ Al KGLEWVSAISDNGGGTYNADS KPGKVPKLLI YAASTLQSG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCAKGEQWGAP SLQPEDVATYYCQKYNSAP FDYWGQGTLVTVSS WTFGQGTKLEIK39D7 131 EVQLLESGGGLVQPGGSLRLS 361 DIVMTQSPLSLPVTPGEPA US20200181281CAASGFTFSSYAMSWVRQAPG SISCRSSQSLLHSNGYNYL Al KGLEWVSTISGSGGSTYYADS DWYLQKSGQSPQLLIYLGS VKGRFTISRDNSKNTLYLQMN NRASGVPDRFSGSGSGTDF S L RAED TAVY YCAT L DT AMAA T LK I S RVEAE DVGV Y YCMQ DAFAIWGQGTMVTVS S ALLIPLYTFGQGTKLEIKDB1 / 163717029.3 120Docket No. 133186-5032-WO18C11 132 EVQLVESGGGLVQPGGSLRLS 362 DIVMTQSPLSLPVTPGEPA US20200181281CAASGFTFSSYWMSWVRQVPG SISCRSSQSLLHSSGHNFL Al KGLEWVANIKQDGSEKYYVDS DWYLKKPGQSPQLLIYLGS VKGRFTISRDNAKNSLYLQMN NRGSGVPDRFSGSGSGTDF S L RAED TAVY YCARD WR S S GW T LK I S RVEAE DVGV Y YCMQ TLDYWGQGTLVTVSS ALQTPRTFGQGTKLEIK38G4 133 EVQLVESGGGLVQPGGSLRLS 363 DIVMTQSPLSLPVTPGEPA US20200181281CAAS GFT FS S YWMS WVRQAP G SISCRSSQSLLHSTGYNFL Al KGLE WVAN VKQ DG S E KD YVD S DWYLQKPGQSPQLLIFLGS VKGRFTISRDNAKNSLYLQMN NRASGVPDRFSGSGSGTDF SLRAEDTAVYYCAREWNSSGW T LK I S RVEAE DVGI Y YCMQ TFDYWGQGTLVTVSS ALQTPLTFGGGTKVEIK27D8 134 QVQLVE S GGGWQ PGRS LRL S 364 EIVMTQSPATLSVSPGERA US20200181281CAASGFTFSSYGMHWVRQAPG TLSCRASQSVSNNLAWYQQ Al KGLEWVAVIWYDGSNKYYADS KPGQAPRLLIYGVSTRATG VKGRFTISRDNSKNTLYLQMN IPARFSGSGSGTEFTLIIS S L RAED TAVYH CARD RV Y YD G SLQSEDFAGYYCQQYNDWP SGSYYNVGVMDVWGQGASVTV LTFGGGTKLEIK SS11A4 135 QVQLVE S GGGWQ PGGS P RL S 365 DIQMTQSPSTLSASVGDRV US20200181281CAAS GFT FS S YAM HWVRQAP G TIT CRAS Q S I S S WLAWYQQ Al TGLEWVALIYYDGSHEYYSDS KPGKAPNLLIYKASSLESG VKGRFT I S RDN S KNT LYLQMS VPSRFSGSGSGTEFTLTIS SLRAEDTAVYYCARDGGSGSH SLQPDDFATYYCQQYNTYY YP FDAFDI WGQGTMVTVS S TFGQGTKVEIK24H1 136 QVQLQESGPGLVKPSETLSLT 366 DIVMTQSPLSLPVTPGEPA US20200181281CTVSGGSISSYYWSWIRQFSG SISCRSSQSLLHSSGYNYL Al KGLEWIGYIYYTGRNNYNPSL DWYLQKPGQSPQLLIYLGS KSRVTISVDTSKNQFSLKLSS DRASGVPDRFRGSGSGTDF VTAADSAVYYCAREGGWGPHF T LK I S RVEAE DVGI Y YCMQ DYWGQGTLVTVSS ALQIP YTFGQGTKLEIK18C02 137 QVQLQQWGAGLLKPSETLSLT 367 DIQMTQSPSSLSASVGDRV US20200181281CAVYGGSFSDYYWSWIRQPPG TITCRASQSISSYLNWFQQ Al KGLEWIGEINHSGSTNYNPSL KPGKAPKLLI YAASSLQSG KSRVTISVDTSKNQFSLKLSS VPSRFSGSGSGTDFTLTIS VTAADTAVYYCARDYDVLTGH SLQPEDFATYYCQQSYTMP FYYYYGMDVWGQGTTVTVS S YTFGQGTKLEIK07C10 138 QVQLVE S GGGWQ PGRS LRL S 368 EIVLTQSPATLSLSPGERA US20200181281CAASGFTFSSYGMHWVRQAPG TLSCRASQSVTNYLAWFQQ Al KGLEWVALIWYDGSNKYYADS KPGQAPRLLIYDAFNRATG VQGRFT I S RDN S KNT LYLQMN IPARFSGSGSGTDFTLTIS SLRAEDTAVYYCAVDYDILTG SLEPEDFAIYYCQQRSYWP HVLYVMDAWGQGVSVTVSS LTFGGGTKLEIK12D9 139 QVQLVE S GGGWQ PGRS LRL S 369 DIQLTQSPSFLSASVGDRV US20200181281CAASGFTFSNYGMNWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVAVIWYDGTIKYYADS KPGKAPKLLI YAASTLQSG VKGRFT I S RDN S KNT LYLQMI VPSRFSGSGSGTEFTLTIS SLRAEDTAVYYCASEYSSGWY SLQPEDFATYYCQQLNSYP RGAFDI WGQGTMVTVS S YTFGQGTKVEIK21F2 140 QVQLVE S GGGWQ PGRS LRL S 370 DIQMTQSPSTLSASVGDRV US20200181281CAASGFTFSSYGMFWVRQTPG TIT CRAS Q S I S S WLAWYQQ Al KGLEWVANIWYDGSNKYYTDS KPGKAPKLLI YKASSLESG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S L RAGD TAVY YCARE T Y Y YG S SLQPDDFATYYCQQYYSYI GS YGGGLDVWGQGTTVTVS S TFGQGTRLEIK25B12 141 QVQLQESGPGLVKPSETLSLT 371 DIQLTQSPSFLSASVGDRV US20200181281CAVS GYSI S SGYYWGWI RQP P TIT CRAS QGI S S YLAWYQQ Al GKGLEWIGSIYHSGSTYYNPS KPGKAPKLLI YAASTLQSG LKSRVTISVDTSKNQFSLKLS VPSRFSGSGSGTEFTLTIS SVTAADTAVYYCARDKI TVAA SLQPEDFATYYCQQLNSYP FDIWGQGTMVTVSS YTFGQGTKLEIKDB1 / 163717029.3 121Docket No. 133186-5032-WO47A2 142 QVQLQESGPGLVKPSETLSLT 372 EIVLTQSPATLSLSPGERA US20200181281CAVS G Y S I S S D Y YWGWI RQ P P TLSCRASQSVRSYLAWYQQ Al GKGLEWIGSIYHSGSTYYNTS KPGQAPRLLIYDASKRATG LKSRVTISLDTSKNQFSLKLT IPARFSGSGSGTDFTLTIS SVTAADTAVYYCVREGTVGGH SLEPEDFAVYYCQQRNSWP YYYYYGMDVWGQGTTVTVS S TFGGGTKVEIK14F11 143 EVHLLESGGGLVQPGGSLRLS 373 DIQLTQSPSFLSASVGDRV US20200181281CAASGFTFSSYAMSWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVSGIDSGGDTYYADSV KPGKAPKLLI YAASTLQSG KGRFTISRDNSKNTLYLQMTS VPSRFSGSGSGTEFTLTIS LRAEDTAVYYCAKDLYSSGWL SLQPEDFAIYYCQQLNSYP AFDI WGQGTMVTVS S LYTFGQGTKLEIK18B2 144 EVQLLESGGGSVQPGGSLRLS 374 DIQLTQSPSFLSASVGDRV US20200181281CAASGFTFSSYAMSWVRQAPG TIT CRAS QGI S T YLAWYQQ Al KGLEWVSGISDNGNTYYADSV KPGKAPKLLI YAASTLQSG KGRFTISRDNSKNTLYLQMNS VPSRFSGSGSGTEFTLTIS LRAEDTAVYHCAKDLYSSGWL SLQPEDFAIYYCQQLNSYP AFDI WGQGTMVTVS S LYTFGQGTKVEIK145 QEQLEESGGDLVKPGASLTLT 375 AFELTQTPASVEADVGGTV US20200181281 CKS S GI DFS SAYYMCWVRQAP TIKCQASQNIYSNLAWYQQ Al GKGL EW I AC I YT G S T Y YANWA KPGQPPKLLI YGASTLASG KGRFTISKTSSTTVTLQMTSL VSSRFRGSGSGTEFTLTIS TAAD TAT Y FCARD P I G YMFD L DLECADAATYYCQGGDDDS WGPGTLLTVSS YAFGGGTEVWK25A11 146 VQLQQPGAELVKPGASVKMSC 376 DIQMTQTTSSLSASLGDRV US20080008719A1 KAS G YT FT S YYMYWVKQRPGQ TISCRASQDISNYLNWYQQ GLEWIGEINPSHGGTNFNEKF KPDGTVKLLIYYTSRLHSG KNKATLTVDKS S S TVYMQLS S VPSRFSGSGSGTDYSLTIS LTSEDSAVYYCTRGGNYPYFA NLEQEDIATYFCQQGNTLP MDYWGQGTSVTVSS WTChimer 147 VQLQQPGAELVKPGASVKMSC 377 DIQMTQTTSSLSASLGDRV US20080008719A1 ic KAS G YT FT S YYMYWVKQRPGQ TISCRASQDISNYLNWYQQ25A11 GLEWIGEINPSHGGTNFNEKF KPDGTVKLLIYYTSRLHSGKNKATLTVDKS S S TVYMQLS S VPSRFSGSGSGTDYSLTIS LTSEDSAVYYCTRGGNYPYFA NLEQEDIATYFCQQGNTLP MD YWGQGT SVTVS SASTKGPS WT FGGGTKLE I KRTVAAPS VFPLAPSSKSTSGGTAALGCL VFIFPPSDEQLKSGTASW VKDYFPEPVTVSWNS GALTS G CLLNNFYPREAKVQWKVDN VHTFPAVLQSS GLYS LS SWT ALQSGNSQESVTEQDSKDS VPS S S LGTQTY I CNVNHKPSN TYSLSSTLTLSKADYEKHK TKVDKRVEPKSCDKTHTCPPC VYACEVTHQGLS S PVTKS F PAPELLGGPSVFLFPPKPKDT NRGEC LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TI SKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQ QGNVFS CSVMHEALHNHYTQK SLSLSPGKhHC4- 148 EVQLVESGGGLVQPGGSLRLS 378 EIVLTQSPATLSLSPGERA US 9346886 B2 H- CAASGFTFNSYGMSWVRQAPG IMS CGAS S S VFYLHWYQQKhumani KGLEWVAT I S S GGS YKYYVD S PGLAPRLWIYDTSKLASGIzed VKGRFTISRDNAKNSLYLQMN PDRFSGSGSGTDFTLTISRS L RAED TAVY YCARH P D YDGV LEPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 149 EVQLVESGGGLVQPGGSLRLS 379 EIVLTQSPATLSLSPGERA US 9346886 B2 c- CAASGFTFNSYGMSWVRQAPG TMSCSVSSSVFYLHWYQQKhumani KGLEWVATISSGGSYTYYPDS PGQAPRLWIYDTSKLASGIzed VKGRFTISRDNAKNSLYLQMN PARFSGSGSGTDFTLTISSS L RAED TAVY YCARH P D YDGV LEPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKDB1 / 163717029.3 122Docket No. 133186-5032-WO hHC4- 150 EVQLVE S GGGLVKPGGS LRL S 380 EIVLTQSPATLSLSPGERA US 9346886 B2 a- CAASGFTFNSYGMSWVRQAPG TLSCRASSSVFYLHWYQQKhumani KGLEWVSTISSGGSYTYYPDS PGQAPRLWIYDTSKLASGIzed VKGRFTISRDNAKNSLYLQMN PARFSGSGSGTDFTLTISSS L RAED TAVY YCARH P D YDGV LEPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 151 EVQLLESGGGLVQPGGSLRLS 381 EIVLTQSPATLSLSPGERA US 9346886 B2 d- CAASGFTFNSYGMSWVRQAPG IMS CRAS S S VFYLHWYQQKhumani KGLEWVSTISSGGSYTYYPDS PGQAPRLWIYDTSKLASGIzed VKGRFTISRDNSKNTLYLQMN PARFSGSGSGTDFTLTISSS L RAED TAVY YCAKH P D YDGV LEPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 152 EVQLLESGGGLVQPGGSLRLS 382 EIVMTQSPATLSLSPGERA US 9346886 B2 04- CAASGFTFNSYGMSWVRQAPG IMS CRAS S S VFYLHWYQQKhumani KGLEWVSTISSGGSYTYYPDS PGQAPRLWIYDTSKLASGIzed VKGRFTISRDNSKNTLYLQMN PARFSGSGSGTDFTLTISSS L RAED TAVY YCARH P D YDGV LQPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 153 EVQLVE S GGGLVKPGGS LRL S 383 EIVLTQSPATLSLSPGERA US 9346886 B2 K- CAASGFTFNSYGMSWVRQAPG TLSCSVSSSVFYVHWYQQKhumani KGLEWVSSISSGGSYIYYADS PGQAPRLLIYDTSKLASGIzed VKGRFTISRDNAKNSLYLQMN PARFSGSGSGTDYTLTISSS L RAED TAVY YCARH P D YDGV LEPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 154 EVQLVE S GGGLVKPGGS LRL S 384 EIVMTQSPATLSVSPGERA US 9346886 B2 K2- CAASGFTFNSYGMSWVRQAPG TLSCSVSSSVFYVHWYQQKhumani KGLEWVSSISSGGSYIYYADS PGQAPRLLIYDTSKLASGIzed VKGRFTISRDNAKNSLYLQMN PARFSGSGSGTEFTLTISSS L RAED TAVY YCARH P D YDGV LQSEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 155 EVQLLESGGGLVQPGGSLRLS 385 EIVLTQSPATLSLSPGERA US 9346886 B2 I- CAAS GFT FNS YAMS WVRQAP G TLSCSVSSSVFYVHWYQQKhumani KGLEWVSAISSGGSYTYYADS PGQAPRLLIYDTSKLASGIzed VKGRFTISRDNSKNTLYLQMN PARFSGSGSGTDFTLTISSS L RAED TAVY YCAKH P D YDGV LEPEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 156 EVQLLESGGGLVQPGGSLRLS 386 EIVMTQSPATLSVSPGERA US 9346886 B2 07- CAAS GFT FNS YAMS WVRQAP G TLSCSVSSSVFYVHWYQQKhumani KGLEWVSTISSGGSYTYYPDS PGQAPRLLIYDTSKLASGIzed VKGRFTISRDNSKNTLYLQMN PARFSGSGSGTEYTLTISSS L RAED TAVY YCAKH P D YDGV LQSEDFAVYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 157 EVQLLESGGGLVQPGGSLRLS 387 DIQMTQSPSSLSASVGDRV US 9346886 B2 03- CAASGFTFNSYGMSWVRQAPG TITCSVSSSVFYVHWYQQKhumani KGLEWVSAISSGGSYTYYPDS PGKAPKLLIYDTSKLASGVzed VKGRFTISRDNSKNTLYLQMN PSRFSGSGSGTDFTFTISSS L RAED TAVY YCAKH P D YDGV LQPEDIATYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 158 EVQLVE S GGGLVKPGGS LRL S 388 DIQMTQSPSSLSASVGDRV US 9346886 B2 b- CAAS GFT FNS YSMNWVRQAP G TITCSVSSSVFYVHWYQQKhumani KGLEWVSSISSGGSYIYYADS PGKAPKLLIYDTSKLASGVzed VKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTDYTFTISSS L RAED TAVY YCARH P D YDGV LQPEDIATYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIKhHC4- 159 QVTLKESGPGILQPSQTLSLT 389 DVLMTQTPLSLPVSLGDQA JP2007112734 A M- CSFSGFSLSTSGMGVSWIRQP SISCRSSQSIVHSDGNTYLhumani SGKGLEWLAHIYWDDDKRYNP EWYLQKPGQSPKLLIYKVSzed SLKSRLTISKDTSRNQVFLKI NRFSGVPDRFSGSGSGTDFT S VD TADT AT Y YCAR S S S Y YD T L KI S RVEAE DL GV Y YC FQ CFAYWGQGTLVTVSA GS HVP YT FGGGT KLEI K4A06 160 EISEVQLVESGGGLVQPGGSL 390 DIQMTQSPSSLSASVGDRV US 20240084030 RL S CAAS GFNL S Y YYI HWVRQ TITCRASQSVSSAVAWYQQ Al AP GKGL EWVAS IYSSSSYTSY KPGKAPKLLIYSASSLYSG ADSVKGRFTISADTSKNTAYL VPSRFSGSRSGTDFTLTISDB1 / 163717029.3 123Docket No. 133186-5032-WOQMNS LRAEDTAVYYCARAYYG SLQPEDFATYYCQQSYYYY FDYWGQGTLVTVS SASTKGPS PIT FGQGT KVEI KRTVAAP VFPLAPSSKSTSGGTAALGCL SVFI FPPSDSQLKS GTASV VKDYFPEPVTVSWNS GALTS G VCLLNNFYPREAKVQWKVD VHTFPAVLQSS GLYS LS SWT NALQSGNSQESVTEQDSKD VPS S S LGTQTY I CNVNHKPSN STYSLSSTLTLSKADYEKH TKVDKKVEPKSCDKTHTCPPC KVYACEVTHQGLSS PVTKS PAPELLGGPSVFLFPPKPKDT FNRGECGGSDYKDDDDK LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TI SKAKGQPREPQVYTLPPIR ELMTSNQVSLSCAVKGFYPSD IAVEWESNGQPENNYKTTPPV LDSDGSFFLVSKLTVDKSRWQ QGNVFS CSVMHEALHNHYTQK SLSLSPGK SID 161 EVQLVESGGGLVQPGGSLRLS 391 DIQMTQSPSSLSASVGDRV US 20240123080 967- CAASGFTFNSYGMSWVRQAPG TITCSVSSSVFYVHWYQQK Al968 KGLEWVAT I S S GGS YKYYVD S PGKAPKLLIYDTSKLASGVVKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTDFTFTISS S L RAED TAVY YCARH P D YDGV LQPEDIATYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIK SID 162 EVQLVESGGDLVKPGGSLKLS 392 QIVLTQSPAIMSASPGEKV US 20240123080 975- CAASGFTFNSYGMSWVRQTPD TMTCS VS S SVFYVHWYQQK Al976 KRLEWVATISSGGSYTYYPDS SGTSPKRWIYDTSKLASGVVKGRFT I S RDNAKNTLYLQMS PARFSGSGSGTSYSLTISS SLKSEDTAMYYCARHPDYDGV MEAEDAATYYCQQWNSNPP WFAYWGQGTLVTVSA TFGGGTKLEIK SID 163 EVQLVQSGAEVKKPGASVKVS 393 EIVLTQSPATLSLSPGERA US 20240123080 983- CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ Al984 QGLEWMGIINPSGGSTSYAQK RPGQAPRLLIYDASNRATGFQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDGVLRYF SLEPEDFAVYYCQQRANVF DWLLDYYYYMDVWGKGTTVTV TFGQGTKVEIK SS SID 164 EVQLVQSGAEVKKPGASVKVS 394 EIVMTQSPATLSLSPGERA US 20240123080 991- CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ Al992 QGLEWMGIINPSGGSTSYAQK KPGQAPRLLIYDASNRATGFQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDAELRHF SLQPEDFAVYYCQQRAQEF DHLLDYHYYMDVWGQGTTVTV TFGQGTKVEIK SSB5- 165 EISEVQLVESGGGLVQPGGSL 395 DIQMTQSPSSLSASVGDRV US 20240026031 CDCP1 RL S CAAS GFNL S Y YYI HWVRQ TITCRASQSVSSAVAWYQQ AlAP GKGL EWVAS IYSSSSYTSY KPGKAPKLLIYSASSLYSG ADSVKGRFTISADTSKNTAYL VPSRFSGSRSGTDFTLTIS QMNS LRAEDTAVYYCARAYYG SLQPEDFATYYCQQSYYYY FDYWGQGTLVTVS S PITFGQGTKVEIK SID 165 EVQLQQSGTVLARPGASVKMS 396 EIVLTQSPLTLSVTIGQPA WO 2023246701 239- CKAS GYS FT I YWVHWVKQRP G SISCKSSQSLLDSDGKTYL Al289 QGLEWIGAVYPGNDDTSYNQN NWLLQRPGQSPKRLIYLVSFKGKAKLTAVT SATTAYMEL S KLDSGVPDRFTGSGSGTDF SLTIDDSAVYYCTRHTYDEVF T L KI S RVEAE DL GV Y YC WQ DYWGQGTTVTVSS GTHFPWTFGGGTKLEIK SID 166 EVQLQQSGTVLARPGASVKMS 397 DIVMTQSPSSLSVSLGDRV WO 2023246701 239- CKAS GYS FT I YWVHWVKQRP G TITCKASEDI YYRLAWYQQ Al290 QGLEWIGAVYPGNDDTSYNQN KPGNAPRLLISGGTNLEAGFKGKAKLTAVT SATTAYMEL S IPSRFSGSGSGKDYTLSIT SLTIDDSAVYYCTRHTYDEVF SLQTEDVAIYYCQHYWNTP DYWGQGTTVTVSS WTFGGGTKLEIK SID 167 EVQLQQSGTVLARPGASVKMS 398 DIQMTQSPSSFSVSLGDRV WO 2023246701 240- CKASGYNFISYWLHWIKQRPG TITCRASEDI YYRLAWYQQ Al291 QGLEWIGGIYPGNTDTTYNQK KPGNAPRLLISGATALETGFKGKAKVT AVT SAT T AYMEL S VPSRFSGSGSGKDYTLSIT SLTNEDSAVYYCIRYDYDRGM SLQTEDVATYYCQHYWNIP DYWGQGTTVTVSS WTFGGGTKLEIKDB1 / 163717029.3 124Docket No. 133186-5032-WOSID 168 EVQLQQSGTVLARPGASVKMS 399 DIVMTQAPAIMSASPGEKV WO 2023246701 241- CKASGYIFLNYWMHWVKQRPG TISCSASSSVSYIYWYQQK Al292 QGLEWIGGIYPGNTDTTYNQK PGSSPKPWIYRTSNLASGVFKGKAKVT AVT SAT T AYMEL S PARFSGSGSGTSYSLTISS SLTNEDSAVYYCIRYDYDRGM MEAEDAATYYCQQYHSYPY DYWGQGTTVTVSS TFGGGTKLEIK SID 169 EVQLQQSGAELVRPGTSVKIS 400 DIVMTQAAFSNPVTLGTSA WO 2023246701 242- CKASGYTFTNYWLGWVKQRPG SISCRSSKSLLHSNGITYL Al293 HGLEWIGDNYPGDNYRNFNEK YWYLQKPGQSPQLLIYQMS FKGKATLTTDASSSTAYLQLS NLASGVPDRFSSSGSGTDF SLISEDSAVYFCTRSGGTRYY TLS I S RVEAGDVGVYYCAQ TMDYWGQGTTVTVS S NLDLPYTFGGGTKLEIK SID 170 EVQLKESGAELVRPGASVKVS 401 DIVMTQS PAS LAVS LGQRA WO 2023246701 243- CKAS GYS FT S YWMNWVKQRP G TISCRASKSVSTSGYSYMH Al294 QGLEWIGMIHPSDSETKLNQK WYQQKPGQPPKLLLYLASNFRDRAS LT VDKS S S TAYMQL S LESGVPARFSGSGSGADFT SPTSEDSAVYYCTINYESFYY LNIHPVEEEDAATYYCLHS AMDYWGQGTTVTVS S RELPYTFGGGTKLEIK SID 171 EVQLKESGPGLVKPSQSLSLT 402 DIVMTQSPLSLPVSLGDQA WO 2023246701 244- CTVTGYSITSDYAWNWIRQFP SISCRSSQSIVHSNGNTYL Al295 GNKLEWMGYI I YS GRT S YNP S EWYLQKPGQSPKLLIYKVS LKSRISITRDTSKNQFFLQLN NRFSGVPDRFSGSGSGTDF SVTTEDTATYYCAREDYYGGS T L KI S RVEAE DL GV Y YC FQ YGGLDYWGQGTTVTVSS GSHVPWTFGGGTKLEIK SID 172 EVKLVESGPGLVKPSQSLSLT 403 EIVLTQSPLSLPVSLGDQA WO 2023246701 245- CTVTGYSITSDYAWNWIRQFP SISCRSRQTLVHTNGNTYL Al296 GNKLEWMGYISYNTYTSYNPS DWYLQKPGQSPKLLIYKVS LKSRISVTRDTSKNQFFLQLK IRFSGVPDRFSGSRSGTDF SVTIEDTATYFCAGGDYYGTG TLKISRVEAEDLGI YYCFQ AVDYWGQGTTVTVSS GSHVPWTFGGGTKLEIK SID 173 EVQLKESGPGLVKPSQSLSLT 404 EIVITQSPASLAVSLGQRA WO 2023246701 246- CSVTGYSITSGYYWNWIRQFP SISCRASESVDHNGISFMN Al297 GNKLDWMGYITYDDSHYYNPS WFQQKPGQPPKLLIYAASN LKDRLSITRDTSKNQFFLKLN QGSGVPARFSGSGSRTDFS SVTAEDTATYFCARGNYYANY LSIHPMEEDDTAIYFCQQN PHAMDYWGQGTTVTVSS KEVPWTFGGGTKLEIK SID 174 EVTLKESGPGLVKPSQSLSLT 405 DIVMTQS PAS LAVS LGQRA WO 2023246701 247- CSVTGYSITSGYYWNWIRQFP TISCRASESVDNSGISFMN Al298 GNKLDWMGYITYDDSHYYNPS WFQQKPGQPPKLLIYAASN LKHRLSITRDTSKNQFFLKLN QGSGVPARFSGSGSRTDFS SVTAEDTATYFCARGNYYANY LSIHPMEEDDTAMYFCQQN PHAMDYWGQGTTVTVSS KEVPWTFGGGTKLEIK SID 175 EVKLVESGPGLVKPSQSLSLT 406 EIVLTQSPLSLPVSLGDQA WO 2023246701 248- CSVTGYSITSGYYWNWIRQFP SISCRSRQTLVHTNGNTYL Al296 GNKLDWMGYITYDDSHYYNPS DWYLQKPGQSPKLLIYKVS LKDRLSITRDTSKNQFFLKLN IRFSGVPDRFSGSRSGTDF SVTAEDTATYFCARGNYYANY TLKISRVEAEDLGI YYCFQ PHAMDYWGQGTTVTVSS GSHVPWTFGGGTKLEIK SID 176 EVKLVESGSSLVKPSQTLSLT 407 DIQMTQSPLSLPVSLGDQA WO 2023246701 249- CSVTGDSITTGYWNWIRKFPG SISCRSGQSIVHSNGKTYL Al299 NKLEYMGYILYSGSTYYNPSL EWYLQKPGQSPKLLIYKVS KSRISITRDTSKNQYYLQLNS TRFSGVPDRFSGSGSGTDF VT T E DT AT Y YCARGD YGAMD Y T L KI T RVEAE DL GV YYC FQ WGQGTTVTVSS GSHVPWTFGGGTKLEIK SID 177 EVKLVESGGGLVKPGGSLKLS 408 DIVMTQSPLTLSITIGQPA WO 2023246701 250- CAASGFTFSTYTMSWVRQTPE SISCRSSQSLLDIDGKTYL Al300 KRLEWVATISSGGIYTYYPDS NWLLQRPGQSPKRLIYLVSVKGRFT I S RDNAKDTLYLQMS ELDSGVPDRFTGSGSGTDF SLRSEDTAVYYCSSPHSYAIS TLKISGVEAEDLGI YYCWQ YGYFDYWGQGTTVTVSS GTHFPYTFGGGTKLEIKDB1 / 163717029.3 125Docket No. 133186-5032-WOSID 178 EVQLKESGGGLVQPGGSLQLS 409 DIQMTQSPSSLAVSVGEKV WO 2023246701 251- CAASGFTFSSYTMSWVRQTLE SMSCKSSQSLLYSNNQRNY Al301 KRLEWVAYISNGGGNTYYPDT LAW YQ QKP GQ S P KL L I YWALKGRFT I S RDNAKNI LYLQLS STWESGVPDRFTGSGSGTA SLKS EDTAMYYCAS S YGNYRG FTLTISSVKAEDLAVYYCQ AWFAYWGQGTTVTVS S QYYSYPWTFGGGTKLEIK SID 179 EVQLKESGGGLVQPGGSLRIS 410 EIVLTQS PAS LAVS LGQRA WO 2023246701 252- CATSGLTFTHYHMSWVRQPPG TISCRASESVDNYGISFMS Al302 KAPEWLAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSQSILYLQ QGSGVPDRFSGSGSGTDFS MNTLRAEDSATYYCVREGGYG LNIHPMEEDDTAMYFCQQS YDGT FAYWGQGTTVTVS S KEVPRTFGGGTKLEIK SID 180 EVQLQQSGGGLVQPGGSLRLS 411 DWMT QT PAS LAVS LGQRA WO 2023246701 253- CATSGLTFTYYHMSWVRQPPG TISCRASESVDNYGISFMN Al303 KAPEWLAIIRNKAYGYTTEYS WFQQKPGQPPKLLIYAASN ASVKGRFTISRDDSQSILYLQ QGSGVPARFSGSGSGTDFS MNTLRTEDSATYYCAREGGYG LNIHPMEEDDTAMYFCQQS YDGT FAYWGQGTTVTVS S KEVPRTFGGGTKLEIK SID 181 EVQLKESGGGLVQPGGSLRIS 412 DIQMTQS PAS LAVS LGQRA WO 2023246701 254- CATSGLTFTHYHMSWVRQPPG TISCRASESVDNYGISFMN Al304 KAPEWLAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSQSILYLQ QGSGVPDRFSGSGSGTDFS MNTLRPEDSATYYCVREGGYG LNIHPMEEDDTAMYFCQQS YDGT FAYWGQGTTVTVS S KEVPRTFGGGTKLEIK SID 182 EVQLKESGPGILQPSQTLSLT 413 DIVMTQAAPSVPVTPGGSV WO 2023246701 255- CSFSGFSLSTSGMGVGWIRQP SISCRSTKSLLHSDGKTYL Al305 SGKGLEWLAHIWWDDVKLYNP YWFLQRPGQSPQLLIYRMS ALKSRLTISKETSNNQVFLKI NLASGVPDRFSGSGSGTAF AS VDAADT AT Y YCAR I D HG YG T L RI S RVEAE DVGV Y YCMQ SNYWDFDVWGAGTTVTVSS HLEYPFTFGSGTKLEIK SID 183 EVKLVESGPGILQPSQTLSLT 414 DIQMTQSPLSLPVSLGDQA WO 2023246701 256- CSFSGFSLSTSGMGVSWVRQP SISCRSSQNIVHTNGNTYL Al306 SGKGLEWLAHIYWDDDKRYNP EWYLQKVGQSPKLLIYKVS SLKGRLTISKDTPRNQVFLEI NRFSGVPDRFSGSGSGTDF TSVDTTDTATYYCARVPGNWD T L KI S RVEAE DL GV YYC FQ EDAMDYWGQGT TVTVS S GS HVP YT FGGGT KLEI K SID 184 EVKLVESGPGILQPSQTLSLT 415 DIVMTQAALSLPVSLGDQA WO 2023246701 257- CSFSGFSLSTSGMGVSWIRQP SISCRSSQNIVYTNGITYL Al307 SGKGLEWLAHIYWDDEKRYNP EWYLQKPGQSPKLLIYKVS SLKSRLTISKDTSSNQVFLKI NRFSGVPDRFSGSGSATDF T S VD TADT AT Y YCAREG S AN W T L KI S RVEAE DL GV YYC FQ EAMDYWGQGTTVTVS S S S HVP WT FGGGT KLEI K SID- 185 EVQLKESGPELKKPGETVKIS 416 EIVLTQSPATLSVTPGDRV WO 2023246701 258- CKASGYTLTDFSMHWLKQAPG SLSCRASQSISDFLHWYQQ Al308 KGLKWMGWINTETGAPTYADD RSHESPRLLIKYASQSISGFKGRFALS LDT SANTAYLQIN IPSRFGGSGSGSDFTLNIN NLKNEDTATYFCSRGRDYDPH TVEPEDVGMYYCQSAHS FP FDYWGQGTTVTVSS YTFGGGTKLEIK SID 186 EVQLKESGPELKKPGETVKIS 417 DIVMTQTPLTLSVTIGQPA WO 2023246701 259- CKASGYTFTYYSMHWVKQTPG SISCKSSQSLLDSDGKTYL Al309 KGLKWMGWINTETGEPTYADD NWLLQRPGQSPKRLIYLVS FKGRFAFSLETSDSTAYLQIN KLDSGVPDRFTGSGSGTDF NLKNEDTATYFCANAMDYWGQ T L KI S RVEAE DL GV YYC WQ GT TVTVS S GTHFPHTFGGGTKLEIK SID 187 EVQLQQSGPELKKPGETVKIS 418 DIVMTQSHKFMSTSVGDRV WO 2023246701 260- CKASGYTFTDYSMHWVKQAPG S I T CKAS Q DVS T AVAWYRQ Al310 KGLKWMGWINTETGQPTYADD KPGQSPKLLIYWASTRHTGFKGRFAFS LET SAS SAYLQIN VPDRLTGSGSGTDFALTIN NLKNEDTATYFCTRTFYYDYV SVQAEDLALYYCQQHSSTP GDYWGQGTTVTVSS YTFGGGTKLEIK SID 188 EVQLKE S GAELVRS GAS VKL S 419 DIQMTQSPAILSASPGEKV WO 2023246701 261- CTAS GFNI KDYYI HWVKQRP E TMTCRASSSVSYIHWYQQK Al311 QGLEWIGWIDPENGDTEYVPK PGSSPDPWIYATSFLASGVFQGKAT LTADT S S NTAYLQLN PGRFSGSGSGTSYSLTISR SLTSEDTAVYYCNPCGTGPWF LEAEDAATYYCQQWNSSPF AYWGQGTTVTVSS TFGGGTKLEIKDB1 / 163717029.3 126Docket No. 133186-5032-WOSID 189 EVQLKESGAELVRPGASVKLS 420 DWMT QT PAS LAVS LGQRA WO 2023246701 262- CKAS GYT FT S YWI NWVRQRP G TISCRASESVDYSGYSFMH Al312 QGLEWIGNIYPSDSYTNYNQK WYQQKPGQPPKLLIYRASNFKDKAT LT VDKS S S TAYMQL S LESGIPARFSGSGSRTDFT S P T S ED SAVYYCT RCLRRRDW LTINPVEADDVATYYCQQS YFDVWGQGTTVTVS S NEDPYTFGGGTKLEIK SID 190 EVNLKESGPELVKPGASVRIS 421 DIVMTQSPSSMYASLGERV WO 2023246701 263- CKASGYTFTSYYIHWVKQRPG TITCKASQDIKSYLSWYQQ Al313 QGLEWIGWIYPGNVNSKYNEK KPWKSPKTLIYYATSLADGFKGKVT LTADKS S I TAYMQL S VPSRFSGSGSGQDYSLTIS SLTSEDSAVYFCAREDYGHYY SLESDDTATYYCLQYGESP AMDYWGQGTTVTVS S WTFGGGTKLEIK SID 191 EVKL VE S G P GL VAP S Q S L S I T 422 D I VMT QT P AS LAVS LGQ RA WO 2023246701 264- CTVSGFSLTTYGVHWVRQPPG TISCRASESVDSYGNSFMH Al314 KGLEWLWIWSDGNTTYNSAL WYQQKPGQPPKLLIYRASN KSRLSINKDNSKSQVFLKMNS LESGIPARFSGSGSRTDFT LQTDDTAMYYCAKNYRNYDYA LTINPVEADDVATYYCQQS MDYWGQGTTVTVSS NEDPYTFGGGTKLEIK SID 192 EVQLKESGGGLVKPGGSLKLS 423 DIVMTQAAFSNPVTLGTSA WO 2023246701 265- CTASGFTFSVYGMSWVRQTPE SISCRSTKSLLHSNGITYL Al315 KRLEWVATLSGGSNYTYYSDS YWFLQKPGQSPQLLIYQMSVKGRFT I S RDTGKNNLYLQMS NLASGVPDRFSSSGSGTDF SLSSDDTALYYCATEDGLIGT T L RI S RVEAE DVGV Y YCAQ WGDYWGQGTTVTVS S NLELPFTFGGGTKLEIK SID 193 EVQLQQSGGGLVKPGGSLKLS 424 DIVMTQAAFSNPVTLGTSA WO 2023246701 266- CTASGFTFSVYGMSWVRQTPE SISCRSTKSLLHSNGITYL Al316 KRLEWVATLSGGDNYTYYTDS YWYLQKPGQSPQLLIYQMSVKGRFT I S RDTAKNNLYLQMS NLASGVPDRFSSSGSGTDF SLRSEDTALYFCATEDGLIGT T L RI S RVEAE DVGV Y YCAQ WGDYWGQGTTVTVS S NLELPFTFGGGTKLEIK SID 194 EVKLVESGPGILQPSQTLSLT 425 DWMT QT PAS LAVS LGQRA WO 2023246701 267- CSFSGFSLSTSGMGVGWIRQP TISCRASESVDSYGNSFMH Al317 SGKGLEWLAHIWWDDVKRYNP WYQQKPGQPPKLLI YLASN ALKSRLTISKDTSSSQVFLKI LESGVPARFSGSGSRTDFT ASVDTADTATYYCARMGGKVP LTIDPVEADDAATYYCQQN WFAYWGQGTTVTVSS NEDPWTFGGGTKLEIK SID 195 EVTLKESGPELKKPGETVKIS 426 D I VMT QAAAS L S VT VGE T V WO 2023246701 268- CKASGYAFTKYGMNWVKQAPG TITCRASENI YNNLAWYQQ Al318 KDLKFMGWINTYTGEATYADD QQGKS PQLLVYAATNLADG FKGRFDFSLEASASTAFLRIN VPSRFSGSGSGTHYSLKIN NLKNEDTATYFCSRGDDYGTG SLQSEDFGFYYCQHFWGTP GYVL FYWGQGT TVTVS S PTFGGGTKLEIK SID 196 EVT L KE S GAEL VR P GALVKL S 427 DIVMTQSPKFMSTSVGDRV WO 2023246701 269- CKASGFNIKDYYMHWVKQRPE SITCKASQDVSTAVTWYQQ Al319 QGLEWIGWIDPENDNTI YDPK KPGQSPKLLIYWASTRHTG FQGKASITADTSSNTAYLQLS VPDRFTGSGSGTDYTLTIS SLTSEDTAVYYCARFYGSYYY SVQAEDLALYYCQQHYSTP AMDYWGQGTTVTVS S YTFGGGTKLEIK SID 197 EVQL KE S GAEL VR P GALVKL S 428 DWMTQTPALMSASPGEKV WO 2023246701 270- CKASGFNIKDYYMYWVKQRPE TMTCSAS S SVS YMYWYQQK Al320 QGLEWIGWIDPENGNTI YDPK PRSSPKPWIYLTSNLASGV LQGKARITADTSSNTAYLQLS PARFSGSGSGTSYSLTISS SLTSEDTAVYYCAGRLYAMEY MEAEDAAT YYCQQWS S D P F WGQGTTVTVSS TFGGGTKLEIK SID 198 QVQLQQSGPDLVRPGESVKIS 429 DIRMTQSPSSMYASLGERV WO 2023246701 271- CKGSGYTFTDHAIHWVRQSHA TITCKASQDINRFLSWFLQ Al321 KSLEWIGVISFSYDNTKYNQN RPGKAPKTLI YRANNLVEGFKGKATMT VDKS S NTAYMELA VPSRFSGSGSGQDYSLTIS RLTSEDSAIYYCARDCYGSNR NLEYEDMGIYYCLQYDEFP GYFDYWGQGTTLTVSS RTFGGGTKLEIKDB1 / 163717029.3 127Docket No. 133186-5032-WOSID 199 DVKLVESGGGLVKPGGSLKLS 430 DWMT QT P LT LS I T I GQ PA WO 2023246701 272- CAASGFTFSSYTMSWVRQTPE SISCRSSQSLLDIDGKTYL Al322 KRLEWVATISSGGIYTYYPDS NWLLQRPGQSPKRLIYLVSVKGRFT I S RDNAKDT LYLQMN ELDSGVPDRFTGSGSGTDF SLRSEDTAVYYCSSPHSYAIS TLRISGVEAEDLGI YYCWQ YGYFDYWGQGTTLTVSS GTHFPYTFGGGTKLEIK SID 200 DVKLVE S GGGLVE PGGS LKL S 431 DWMT QT P LT LS I T I GQ PA WO 2023246701 273- CAASGFPFSSYTMSWVRQTPE SISCRSSQSLLDFDGKTYL Al323 KRLEWVATISSGGIYTYYPDS NWLLQRPGQSPKRLIYLVSVKGRFT I S RDNAKDTLYLQMS ELDSGVPDRFTGSGSGTDF SLRSEDTAVYYCSSPHSYAIS TLKISGVEAEDLGI YYCWQ YGYFDYWGQGTTLTVSS GTHFPFTFGGGTKLEIK SID 201 QVQLQQSGAELVRPGTSVKIS 432 DIVMTQAAFSNPVTLGTSA WO 2023246701 274- CKASGYTFTNYWLGWVKQRPG SISCRSSRSLLHNNGITYL Al324 HGLEWIGDNYPGDNYRNFNEK YWYLQKPGQSPQLLIYQMS FKGKATLTTDASSSTAYLQLS NLASGVPDRFHSSGSGTDF SLISEDSAVYFCTRSGGSRYY T L S I S RVEAE DVGV Y YCAQ TMDYWGQGTSVTVSS NLDLPYTFGGGTKLEIK SID 202 QVQLRESGPGLVAPSQSLSIT 433 QIVLTQSPAIKSASPGEKV WO 2023246701 275- CTVSGFSLTDFGVNWVRQPPG TMTCSAS S SVI YMHWYQQK Al325 KGLEWLGI IWANGRI EYNSAL SGSSPKRWIYDTSKLASGVKS RL S I S KDNS RS QVFLKLN S PVRFSGSGSGTSYSLTIST LQTDDTARYYCARDHDYDVEA MEAEDAATYYCQQWSSYPP MDYWGQGTSVTVSA TFGGGTKVEIK SID 203 QGQMQQSGAELVKPGASVKLS 434 SIVMTQTPKFLLVSAGDRV WO 2023246701 276- CKTSGFTFNSS YITWLKQKPG TITCKASQSVNTDVAWYQQ Al326 QSLEWIAWIFAGTGGTYYNEK KSGQSPKLLIYSASNRYTG FTDKAQLTVDTTSSTAYMQFS VPDRFTGSGYGTDFTFTIS SLTTEDSAIYYCARHGLGYDY TVQAEDLAVYFCQQDHS S P WGQGTTLTVSS PWTFGGGTKLEIK SID 204 QVQLQQSGPELVS PGESVKI S 435 DIKMTQSPSSIYVSPGERV WO 2023246701 277- CKGSGYTFTDYAVHWVKQSHS TITCKASQDINSFLSWFQQ Al327 KSLEWIGVKSVYYGITKYSQN KPGKSPKTLIYRANRLVDGFKDKATMT VDKS S S TAYMELA VPSRFSGSGSGQDYSLTIS RLTSEDSAIYYCARDSYGSSR SLEYEDMGIYYCLQYDEFP GYFDYWGQGTTLTVSS RTFGGGTKLEIK SID 205 QVTLKESGPGILKPSQTLSLT 436 QAWTQESALTTSPGETVT WO 2023246701 278- CSFSGFSLSTSGVGVGWIRQP LTCRSSTGAVATSNYANWV Al328 SGKGLEWLAHIWWDDEKYYNP QEKPDHLFTGLIGGTNNRV SLKSHFTISKDTSRNQVFLKI PGVPARFS GS LI GDKAALT TSVDTADTATYYCVKEGDGMD ITGAQTEDEAIYFCALWYS YWGQGTSVTVSS NHWVFGGGTKLTVL SID 206 DVKLVESGGGLVKPGGSLKLS 437 DWMT QT P LT LS I T I GQ PA WO 2023246701 279- CAAS GFT FS S FTMSWVRQT P E SISCKSSQSLLDSDGKTYL Al329 KRLEWVATISSSGSYTYYPDS TWLLQRPGQSPKRLIFLVSVKGRFT I S RDNAKNTLYLQMS KLDSGVPDRFTGSGSGTDF SLKSEDTAMYYCTSPDYYGRS T L KI S RVEAE DL GV YYCWQ YGYFDYWGQGTTLTVSS GTHFPYTLGGGTKLEIK SID 207 QVTLKESGPGILQPSQTLSLT 438 DVLMTQTPLSLSVSLGDQA WO 2023246701 280- CSFSGFSLSTSGMGVSWFRQP SISCRSSQTIVYSNGNSYL Al330 SGKGLEWLAHI YWDDDKRYNP EWYLQKPGQSPKLLIYKVS SLKSRLTISKDTSSNQVFLRI NRFSGIPDRFSGSGSGTDF TNVDTSDTATYYCTREGSADW TLKISRVEAEDLGI YYCFQ EALDYWGQGTSVTVSS S S HVP WT FGGGT KLEI K SID 208 EVQLQQSGAELVKPGASVKLS 439 DIVLTQS PAS LAVS LGQRA WO 2023246701 281- CTAS GFNI QDT YI LWVKQRP E TISCRASQSVSTSSYSYMH Al331 QGLEWIGGIDPANDNTNYGPN WYQLKPGQPPKLLIKYASNFQGKAT I TADT S S NTAYLQL S LESGVPARFSGSGSGTDFT SLTSEDSAVYYCAREDAYPWF LNIHPVEEEDAAIYYCQHN AYWGQGTLVTVSS WEIPWTFGGGTRLEIKDB1 / 163717029.3 128Docket No. 133186-5032-WOSID 209 QVQLQQSGAELMKPGASVKIS 440 DVQ I T Q S P S YLAAS P GEAI WO 2023246701 282- CKAT GYT FS RYWVEWVKQRP G TINCRTSKSIGKYLAWYQE Al332 HGLEWIGDILPGSDFTNYNEK KPGKTNKLLIYSGSTLQSGFKGKAT FT ADS S S NTAYMQL S IPSRFSGSGSGTDFTLTIT S LT S ED SAVYYCARKD Y YGN Y SLEPEDFAMYYCQQHDEYP DYAMDYWGQGT S VTVS S WTFGGGTKLDIK SID 210 EVKLVE S GGGLVQ PGGS LRL S 441 DIVMTQSHKFMSTSVGDRV WO 2023246701 283- CATSGFTFSDFYMEWVRQPPG S I TCKAS QDVS S S VAWYQQ Al333 KRLEWIAVSRDKTNDYTTEYS KPGQSPKLLIYWASTRHTG ASMKGRFIVSRDTSQSILYLQ VPDRFTGSGSGTDYTLTIS MNALRAEDTAI YYCARDGVYY SVQAEDLALYYCQQHYNTP YGSS YTLDYWGQGTSVTVSS PTFGGGTKLEIK SID 211 QVQLQQSGNEWKPGASVKLS 442 ENVLTQSPAIMSASSGEKV WO 2023246701 284- CKTSGYTFTNYWLQWVKQRPG TMTCRASSSVRSSYLHWYQ Al334 QGLEWIGEIFPGTGTTYYNEK QKSGASPKVWIYSTSNLASFKDQAT VT I DT S S S TAYI HL S GVPVRFSGSGSGTSYSLTI SLTSEDSAVYFCARTNWEGYY S S VEAEDAAT YYCQQYS GS FDYWGQGTTLTVSS PSWTFGGGTKLEIK SID 212 EVKLVESGGGLVKPGGSLKLS 443 DIQMTQSPSSLSASLGERV WO 2023246701 285- CAASGFTFSSYGMSWVRQTPE SLTCRASQEISGYLTWLQQ Al335 KRLEWVATISGGINYTYYRDS RPDGTIKRLI YAASTLDSGVE GR FT I S RDNAKNN L YLQM S VPKRFSGSRSGSDYSLTIS RLRSEDTALYYCARHDRYDGY SLESEDFADYYCLQYASYP YYVMDYWGQGT S VTVS S YTFGGGTKLEIK SID 213 QVQLQQSGPELVRPGVSVRIS 444 DIQMTQSTSSLSASLGDRV WO 2023246701 286- CKGS GYPFTDYAI HWVKQGHG TITCRASQDITNYLNWYQQ Al336 KNLEWIGVIAPYSDNTGYNQR KPDGTVKLLIYYTSRLHSGFKGKATMT VDKS S S TAYMELA VPSRFSGSGSGTDFSLTIS RLT S ED SAI YYCAAYGN YGY Y NLEQEDIATYFCQQGNTLP TMDYWGQGTSVTVSS WTFGGGTKLEII SID 214 QVTLKESGPGILQPSQTLSLT 445 QIVLTQS PALMTAS PGEQV WO 2023246701 287- CSFSGFSLSTSGMSVGWIRQP TMTCSASSSVSYIHWYQQK Al337 SGKGLEWLAHIWWNDDKYYNP SGTSPKRWIYDASKLASGV ALKTRLTISKDSSNNQIFLKI PARFSGSGSGTSYSLTISS ASWTADSATYYCARIGYYYG MEAEDAATYYCQQWSSYPL TYALDYWGPGTSVTVSS TFGGGTKLELK SID 215 QVTLKESGPGILQPSQTLSLT 446 DIQMTQTTSSLSASLGDRV WO 2023246701 288- CSFSGFSLTTSGMNVGWLRQP TISCSASQAISNYLNWYQQ Al338 SGKGLEWLAHIWWNDDKHSNP KPDGTVKLLIYYTSHLHSG VLKSRLTISKDTSNNQAFLKI VPSRFSGSGSGTDYSLTIS ANWTADSATYYCARLRDGGF NLEPEDIATYYCQQYSKIP AYWGQGTLVTVSA WTFGGGTKLEII SID 216 QVQLVQSGAEVKKPGASVKVS 447 DIQMTQSPSSLSASVGDRV WO 2023246701 339- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al351 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVTMT RDT STS T VYMEL S VPSRFSGSGSGKDYTFTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 216 QVQLVQSGAEVKKPGASVKVS 448 DIQMTQSPSSLSASVGDRV WO 2023246701 339- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al352 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVTMT RDT STS T VYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 216 QVQLVQSGAEVKKPGASVKVS 449 DIQMTQSPSSLSASVGDRV WO 2023246701 339- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al353 QGLEWMGGIYPGNTDTTYNQK KPGNAPKLLISGATALETGFKGRVTMT RDT STS T VYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIKDB1 / 163717029.3 129Docket No. 133186-5032-WOSID 217 QVQLVQSGAEVKKPGASVKVS 447 DIQMTQSPSSLSASVGDRV WO 2023246701 340- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al351 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVTMTADT STS T VYMEL S VPSRFSGSGSGKDYTFTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 217 QVQLVQSGAEVKKPGASVKVS 448 DIQMTQSPSSLSASVGDRV WO 2023246701 340- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al352 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVTMTADT STS T VYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 217 QVQLVQSGAEVKKPGASVKVS 449 DIQMTQSPSSLSASVGDRV WO 2023246701 340- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al353 QGLEWMGGIYPGNTDTTYNQK KPGNAPKLLISGATALETGFKGRVTMTADT STS T VYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 218 QVQLVQSGAEVKKPGASVKVS 447 DIQMTQSPSSLSASVGDRV WO 2023246701 341- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al351 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVTMTADT STS TAYMEL S VPSRFSGSGSGKDYTFTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 218 QVQLVQSGAEVKKPGASVKVS 448 DIQMTQSPSSLSASVGDRV WO 2023246701 341- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al352 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVTMTADT STS TAYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 218 QVQLVQSGAEVKKPGASVKVS 449 DIQMTQSPSSLSASVGDRV WO 2023246701 341- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al353 QGLEWMGGIYPGNTDTTYNQK KPGNAPKLLISGATALETGFKGRVTMTADT STS TAYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 219 QVQLVQSGAEVKKPGASVKVS 447 DIQMTQSPSSLSASVGDRV WO 2023246701 342- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al351 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVT VTAVT STS T VYMEL S VPSRFSGSGSGKDYTFTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 219 QVQLVQSGAEVKKPGASVKVS 448 DIQMTQSPSSLSASVGDRV WO 2023246701 342- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al352 QGLEWMGGIYPGNTDTTYNQK KPGKAPKLLISGATALETGFKGRVT VTAVT STS T VYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 219 QVQLVQSGAEVKKPGASVKVS 449 DIQMTQSPSSLSASVGDRV WO 2023246701 342- CKAS GYN FIS YWL HWVRQAP G TITCRASEDI YYRLAWYQQ Al353 QGLEWMGGIYPGNTDTTYNQK KPGNAPKLLISGATALETGFKGRVT VTAVT STS T VYMEL S VPSRFSGSGSGKDYTLTIS SLRS EDTAVYYCI RYDYDRGM SLQPEDIATYYCQHYWNIP DYWGQGTLVTVSS WTFGQGTKVEIK SID 220 EVQLVE S GGGLVQ PGRS LRL S 450 DIQMTQSPSSLSASVGDRV WO 2023246701 343- CTASGLTFTHYHMSWFRQAPG TITCRASESVDNYGISFMN Al354 KGLEWVAIIRNKAYGYTTDYS WFQQKPGQAPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I KDB1 / 163717029.3 130Docket No. 133186-5032-WOSID 220 EVQLVE S GGGLVQ PGRS LRL S 451 DIQMTQSPSSLSASVGDRV WO 2023246701 343- CTASGLTFTHYHMSWFRQAPG TITCRASESVDNYGISFMN Al355 KGLEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 220 EVQLVE S GGGLVQ PGRS LRL S 452 DIQMTQSPSSLSASVGDRV WO 2023246701 343- CTASGLTFTHYHMSWFRQAPG TITCRASESVDNYGISFMN Al356 KGLEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYFCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 221 EVQLVE S GGGLVQ PGRS LRL S 450 DIQMTQSPSSLSASVGDRV WO 2023246701 344- CTTSGLTFTHYHMSWVRQAPG TITCRASESVDNYGISFMN Al354 KGLEWVAIIRNKAYGYTTDYS WFQQKPGQAPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 221 EVQLVE S GGGLVQ PGRS LRL S 451 DIQMTQSPSSLSASVGDRV WO 2023246701 344- CTTSGLTFTHYHMSWVRQAPG TITCRASESVDNYGISFMN Al355 KGLEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 221 EVQLVE S GGGLVQ PGRS LRL S 452 DIQMTQSPSSLSASVGDRV WO 2023246701 344- CTTSGLTFTHYHMSWVRQAPG TITCRASESVDNYGISFMN Al356 KGLEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYFCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 222 EVQLVE S GGGLVQ PGRS LRL S 450 DIQMTQSPSSLSASVGDRV WO 2023246701 345- CTTSGLTFTHYHMSWVRQAPG TITCRASESVDNYGISFMN Al354 KGPEWVAIIRNKAYGYTTDYS WFQQKPGQAPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 222 EVQLVE S GGGLVQ PGRS LRL S 451 DIQMTQSPSSLSASVGDRV WO 2023246701 345- CTTSGLTFTHYHMSWVRQAPG TITCRASESVDNYGISFMN Al355 KGPEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 222 EVQLVE S GGGLVQ PGRS LRL S 452 DIQMTQSPSSLSASVGDRV WO 2023246701 345- CTTSGLTFTHYHMSWVRQAPG TITCRASESVDNYGISFMN Al356 KGPEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYFCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 223 EVQLVE S GGGLVQ PGRS LRL S 450 DIQMTQSPSSLSASVGDRV WO 2023246701 346- CTTSGLTFTHYHMSWVRQPPG TITCRASESVDNYGISFMN Al354 KAPEWVAIIRNKAYGYTTDYS WFQQKPGQAPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 223 EVQLVE S GGGLVQ PGRS LRL S 451 DIQMTQSPSSLSASVGDRV WO 2023246701 346- CTTSGLTFTHYHMSWVRQPPG TITCRASESVDNYGISFMN Al355 KAPEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYYCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I KDB1 / 163717029.3 131Docket No. 133186-5032-WOSID 223 EVQLVE S GGGLVQ PGRS LRL S 452 DIQMTQSPSSLSASVGDRV WO 2023246701 346- CTTSGLTFTHYHMSWVRQPPG TITCRASESVDNYGISFMN Al356 KAPEWVAIIRNKAYGYTTDYS WFQQKPGQPPKLLIYAASN ASVRGRFTISRDDSKSILYLQ QGSGVPSRFSGSGSGTDFT MNSLKTEDTAVYYCVREGGYG LTISSMQPEDFATYFCQQS YDGT FAYWGQGTLVTVS S KEVPRT FGGGTKVE I K SID 224 QVQLVQSGSELKKPGASVKVS 453 EIVLTQSPATLSLSPGERA WO 2023246701 347- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al357 QGLEWMGWINTETGAPTYADD KPGQAPRLLIKYASQSISGFKGRFVFS LDT SVSTAYLQI S IPARFSGSGPGSDFTLTIS SLKAEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 224 QVQLVQSGSELKKPGASVKVS 454 EIVLTQSPATLSLSPGERA WO 2023246701 347- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al358 QGLEWMGWINTETGAPTYADD KPGQSPRLLIKYASQSISGFKGRFVFS LDT SVSTAYLQI S IPARFSGSGSGSDFTLTIS SLKAEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 224 QVQLVQSGSELKKPGASVKVS 455 EIVLTQSPATLSLSPGERA WO 2023246701 347- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al359 QGLEWMGWINTETGAPTYADD KSGQSPRLLIKYASQSISGFKGRFVFS LDT SVSTAYLQI S IPARFSGSGSGSDFTLTIS SLKAEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 225 QVQLVQSGSELKKPGASVKVS 453 EIVLTQSPATLSLSPGERA WO 2023246701 348- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al357 QGLEWMGWINTETGAPTYADD KPGQAPRLLIKYASQSISGFKGRFVLS LDT SVSTAYLQI S IPARFSGSGPGSDFTLTIS SLKAEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 225 QVQLVQSGSELKKPGASVKVS 454 EIVLTQSPATLSLSPGERA WO 2023246701 348- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al358 QGLEWMGWINTETGAPTYADD KPGQSPRLLIKYASQSISGFKGRFVLS LDT SVSTAYLQI S IPARFSGSGSGSDFTLTIS SLKAEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 225 QVQLVQSGSELKKPGASVKVS 455 EIVLTQSPATLSLSPGERA WO 2023246701 348- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al359 QGLEWMGWINTETGAPTYADD KSGQSPRLLIKYASQSISGFKGRFVLS LDT SVSTAYLQI S IPARFSGSGSGSDFTLTIS SLKAEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 226 QVQLVQSGSELKKPGESVKVS 453 EIVLTQSPATLSLSPGERA WO 2023246701 349- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al357 QGLEWMGWINTETGAPTYADD KPGQAPRLLIKYASQSISGFKGRFVLS LDT SVSTAYLQI S IPARFSGSGPGSDFTLTIS SLKSEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 226 QVQLVQSGSELKKPGESVKVS 454 EIVLTQSPATLSLSPGERA WO 2023246701 349- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al358 QGLEWMGWINTETGAPTYADD KPGQSPRLLIKYASQSISGFKGRFVLS LDT SVSTAYLQI S IPARFSGSGSGSDFTLTIS SLKSEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 226 QVQLVQSGSELKKPGESVKVS 455 EIVLTQSPATLSLSPGERA WO 2023246701 349- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al359 QGLEWMGWINTETGAPTYADD KSGQSPRLLIKYASQSISGFKGRFVLS LDT SVSTAYLQI S IPARFSGSGSGSDFTLTIS SLKSEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIKDB1 / 163717029.3 132Docket No. 133186-5032-WOSID 227 QVQLQQSGSELKKPGESVKLS 453 EIVLTQSPATLSLSPGERA WO 2023246701 350- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al357 QGLKWMGWINTETGAPTYADD KPGQAPRLLIKYASQSISGFKGRFVFS LDT SVSMAYLQI S IPARFSGSGPGSDFTLTIS SLKSEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 227 QVQLQQSGSELKKPGESVKLS 454 EIVLTQSPATLSLSPGERA WO 2023246701 350- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al358 QGLKWMGWINTETGAPTYADD KPGQSPRLLIKYASQSISGFKGRFVFS LDT SVSMAYLQI S IPARFSGSGSGSDFTLTIS SLKSEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK SID 227 QVQLQQSGSELKKPGESVKLS 455 EIVLTQSPATLSLSPGERA WO 2023246701 350- CKASGYTLTDFSMHWVRQAPG TLSCRASQSISDFLHWYQQ Al359 QGLKWMGWINTETGAPTYADD KSGQSPRLLIKYASQSISGFKGRFVFS LDT SVSMAYLQI S IPARFSGSGSGSDFTLTIS SLKSEDTAVYYCSRGRDYDPH SVEPEDFAVYYCQSAHS FP FDYWGQGTLVTVSS YTFGQGTKLEIK CDCP1- 228 EVQLVESGGGLVQPGGSLRLS 456 DIQMTQSPSSLSASVGDRV US 20230265206 001 CAASGFNLSYYYIHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVASIYSSSSYTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARAYYGFDY SLQPEDFATYYCQQSYYYY WGQGTLVTVSS PITFGQGTKVEIK CDCP1- 229 EVQLVESGGGLVQPGGSLRLS 457 DIQMTQSPSSLSASVGDRV US 20230265206 002 CAASGFNISYYSMHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVASISPYSGYTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARGYYALDY SLQPEDFATYYCQQYYYFY WGQGTLVTVSS PFTFGQGTKVEIK CDCP1- 230 EVQLVESGGGLVQPGGSLRLS 458 DIQMTQSPSSLSASVGDRV US 20230265206 003 CAASGFNISYYYMHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVASIYSSYGYTSY ADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARVYYGFDY SLQPEDFATYYCQQSYYVY WGQGTLVTVSS PITFGQGTKVEIK CDCP1- 231 EVQLVESGGGLVQPGGSLRLS 459 DIQMTQSPSSLSASVGDRV US 20230265206 004 CAASGFNISYYYIHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVASIYPYYGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARAYYGFDY SLQPEDFATYYCQQSYWSF WGQGTLVTVSS PITFGQGTKVEIK CDCP1- 232 EVQLVESGGGLVQPGGSLRLS 460 DIQMTQSPSSLSASVGDRV US 20230265206 005 CAASGFNLYYSYMHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVAYISPYSGSTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARYSY SALD SLQPEDFATYYCQQSSWHY YWGQGTLVTVSS HLFTFGQGTKVEIK CDCP1- 233 EVQLVESGGGLVQPGGSLRLS 461 DIQMTQSPSSLSASVGDRV US 20230265206 006 CAASGFNIYSYYIHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVASIYPYYGYTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARAYYGMDY SLQPEDFATYYCQQSYFYW WGQGTLVTVSS PITFGQGTKVEIK CDCP1- 234 EVQLVESGGGLVQPGGSLRLS 462 DIQMTQSPSSLSASVGDRV US 20230265206 007 CAASGFNISSYYMHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVASIYPYSGYTYYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARAYYAMDY SLQPEDFATYYCQQSYYVY WGQGTLVTVSS PITFGQGTKVEIKDB1 / 163717029.3 133Docket No. 133186-5032-WOCDCP1- 235 EVQLVESGGGLVQPGGSLRLS 463 DIQMTQSPSSLSASVGDRV US 20230265206 008 CAASGFNLYSYYIHWVRQAPG TITCRASQSVSSAVAWYQQ Al KGLEWVASIYPYYSSTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARYYYAMDY SLQPEDFATYYCQQGYAGS WGQGTLVTVSS WHPITFGQGTKVEIK CDCP1- 236 EVQLVESGGGLVQPGGSLRLS 464 DIQMTQSPSSLSASVGDRV US 20230265206 009 CAASGFNI YSYSMHWVRQAPG TITCRASQSVSSAVAWYQQ Al KGLEWVASISPYYSYTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARAYYALDY SLQPEDFATYYCQQSYWYY WGQGTLVTVSS PITFGQGTKVEIK CDCP1- 237 EVQLVESGGGLVQPGGSLRLS 465 DIQMTQSPSSLSASVGDRV US 20230265206 010 CAASGFNISYYYMHWVRQAPG TITCRASQSVSSAVAWYQQ Al KGLEWVASIYSSSSYTSYADS KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARSYYAMDY SLQPEDFATYYCQQSYYVY WGQGTLVTVSS PITFGQGTKVEIK CDCP1- 238 EVQLVESGGGLVQPGGSLRLS 466 DIQMTQSPSSLSASVGDRV US 20230265206 011 CAASGFNFSSSSIHWVRQAPG TITCRASQSVSSAVAWYQQ AlKGLEWVAS I S S S YGYT YYAD S KPGKAPKLLIYSASSLYSG VKGRFTISADTSKNTAYLQMN VPSRFSGSRSGTDFTLTIS SLRAEDTAVYYCARTVRGSKK SLQPEDFATYYCQQSSYSL P YFS GWAMDYWGQGTLVTVS S ITFGQGTKVEIKRefere 239 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366 nee CAASGFTFSNYAMNWVRQAPG TITCRASQGISSYLAWYQQ Alchain KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGGVKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S LRAEDTAVYYCAKE SIT I VI SLQPEDFATYYCQHLNRFP VRGVIVIDYYGMDVWGQGTTV RTFGQGTKVEIK TVSSM103F 240 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366CAASGFTFSNYAMNWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS SLRAEDTAVYYCAKESITFVR SLQPEDFATYYCQHLNRFP GVIVIDYYGMDVWGQGTTVTV RTFGQGTKVEIKssM103F- 241 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366 M108L CAASGFTFSNYAMNWVRQAPG TITCRASQGISSYLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS SLRAEDTAVYYCAKESITFVR SLQPEDFATYYCQHLNRFP GVLDYYGMDVWGQGTTVTVSS RTFGQGTKVEIKM103K 242 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366CAASGFTFSNYAMNWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S L RAED TAVY YCAKE SIT KVR SLQPEDFATYYCQHLNRFP GVIVIDYYGMDVWGQGTTVTV RTFGQGTKVEIK SSM103K- 243 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366 M108L CAASGFTFSNYAMNWVRQAPG TITCRASQGISSYLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S L RAED TAVY YCAKE SIT KVR SLQPEDFATYYCQHLNRFP GVLDYYGMDVWGQGTTVTVSS RTFGQGTKVEIKM103L 244 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366CAASGFTFSNYAMNWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S L RAED TAVY YCAKE SIT LVR SLQPEDFATYYCQHLNRFP GVMDYYGMDVWGQGTTVTVSS RTFGQGTKVEIKDB1 / 163717029.3 134Docket No. 133186-5032-WOM103L- 245 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366 M108L CAASGFTFSNYAMNWVRQAPG TITCRASQGISSYLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS S LRAEDTAVYYCAKE SIT I VR SLQPEDFATYYCQHLNRFP GVLDYYGMDVWGQGTTVTVS RTFGQGTKVEIK SM108L 246 EVQLLESGGGLVQPGGSLRLS 467 DIQLTQSPSFLSASVGDRV WO 2024127366CAASGFTFSNYAMNWVRQAPG TIT CRAS QGI S S YLAWYQQ Al KGLEWVSAISGGGGSTYYADS KPGKAPKLLI YAASTLQGG VKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTEFTLTIS SLRAEDTAVYYCAKESITNIV SLQPEDFATYYCQHLNRFP RGVLDYYGMDVWGQGTTVTVS RTFGQGTKVEIKS2B5 247 CAGGTGCAGCTGAAGCAGTCA 468 GACAT CCAGAT GAC T CAGT WO 2024090927A1 GGACCTGGCCTAGTGCAGCCC CTCCAGCCTCCCTATCTGC TCACAGAGCCT GT CCAT CACC ATCTGTGGGAGAAACTGTC TGCACAGTCTCTGGTTTCTCA ACCAT CACAT GT CGAGCAA TTAACTAACTATGGTGTACAC GT GAGAAT AT T T ACAGT TA TGGGTTCGCCAGTCTCCAGGA T T T AGCAT GGTAT CAGCAG AAGGGT CT GGAGT GGCT GGGA AAACAGGGAAAAT C T CC T C GTGATATGGAGTGGTGGAAGC AGCTCCTGGTCTATAATGC ACAGAC TATAAT GCAGC T T T C AAAAACCT TAGTAGAAGGT AT AT CCAGACT GAGCAT CGAC GTGCCATCAAGGTTCAGTG AAGGACAAT T C CAAGAGCCAA GCAGT GGAT CAGGCACACA GT T T T C T T TAAAAT GAACAGT GT T T T CT C T GAAGAT CAAC CT GCAAGC TAAT GACACAGC C AGC CT GCAGC CT GAAGAT T ATATAtTACTGTGCCAGAAAT T T GGGAGT TAT T AC T GT CATGGGAT CT GGGGGCT GT GGAC ACAT CAT TAT GGTAGT C CG TACTGGGGTCAAGGAACCTCA TACACGTTCGGAGGGGGGA GTCACCGTCTCCTCA CCAAGCTGGAAATAAAA4H4 248 GAGGTGCAGCTGGTGGAGTCT 469 CAAAT T GT T C T CAC CCAGT WO 2024090927A1 GGGGGAGACTTAGTGAAGCCT CTCCAGCAATCATGTCTGC GGAGGGTCCCTGAAACTCTCC GT C T C CAGGGGAGAAGGT C TGTGCAGCCTCTGGATTCACT ACCATGACCTGCAGTGCCA T T CAGT AGCTAT GGCAT GT C T GCTCAAGTGTATITTTACAT TGGGTTCGCCAGACTCCTGAC T CACT GGCAC CAACAGAAG AAGAGGCT GGAGT GGGT CGCA TCAGGCAACTCCCCCAAAA ACCATTAGTACTGGTGGTAGT GAT GGAT T TAT GACACAT C TACACCTACTATCCAGACAGT CAAAGTGGCTTCTGGAGTC GT GAAGGGGCGAT TCACCAT C CCTACTCGCTTCAGTGGCA T C CAGAGACAAT GCCAAGAAC GTGGGTCTGGGACCTCTTA ACCCTGTACCTGCAAATGAGC CT C T C T CACAAT CAACAGC AGT C T GAAGT C T GAGGACACA AT GGAGGC T GAAGAT GC T G GC CAT GTAT T T CT GT GCAAGA CCACTTATTACTGCCAGCA CATAAT GAT TACAAC GAGGT T GTGGAGTAGTAACGCACTC GCTTTGGACTACTGGGGTCAA ACGTTCGGTGCTGGGACCA GGAACCTCAGTCACCGTCTCC AGCTGGAGCTGAAA TCA2F9 249 GAAGTGCAGCTGGTGGAGTCT 470 CAAAT T GT T C T CAC CCAGT WO 2024090927A1 GGGGGAGGCTTAGTGAAGCCT CTCCAGCAATCATGTCTGC GGAGGGTCCCTGAAACTCTCC AT C T C CAGGGGAGAAGGT C TGTGCAGCCTCTGGATTCACT ACCATGACCTGCAGTGCCA TTCAGTAGCTATGCCATGTCT GCTCAAGTGCAAATTTCAT TGGGTTCGCCAGACTCCGGAG GCACT GGT AC CAGCAGAAG AAGAGGCT GGAGT GGGT CGCA TCAGGCACCTCCCCCAAAA ACCATTAGTAGTGGTGGTCGT GAT GGAT T TAT GACACAT C TACACCTACTATCCAGACAGT CAAACTGGCTTCTGGAGTC GT GAAG GG T C GAT T C AC CAT C CCTGCTCGCTTCAGTGGCA T C CAGAGACAAT GCCAAGAAC GTGGGTCTGGGACCTCTTA ACCCTGTACCTGCAAGTGAGC CT C T C T CACAAT CAGCAGC AGTCTGAGGTCTGAGGACACG AT GGAGGC T GAAGAT GC T G GC CAT GTAT TACT GT GCAGGA CCACTTATTACTGCCAGCA CATGCCGATTACGTCGACGTG GT GGAGTAGT AACC CAC GT GTCTTTGACTTCTGGGGCCAA TCGGAGGGGGGACCAAGCT GGCACCACTCTCACAGTCTCC GGAAATAAAA TCA1E12- 471 EVQL VQ S GAEVKK P GAT VKI S 519 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC1 / LC CKVSGFNIKDGYMHWVQQAPG (288) TITCRASQDINNYLNWYQQ2 KGLEWMGLVDPENGDTIYAEK KPGKVPKLLI YYTSRLHSGFQGRVTITADTSTDTAYMELS VPSRFSGSGSGTDFTLTISDB1 / 163717029.3 135Docket No. 133186-5032-WOSLRSEDTAVYYCATSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 472 QVQLVQSGAEVKRPGASVKLS 520 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC7 / LC CTASGFNIKDGHMHWVRQAPG TISCRASQDINNYLNWYQQ3 QGLEWIGWIDPENGDLEYAQK KPGKAPKLLI YYTSRLHSGFQGRVTLTADTSSNTAYLQLS VPSRFSGSGSGTDFTLTIS SLTSEDTAVYYCTTSRRGYFF NLQPEDIATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 473 EVQL VQ S GAEVKK P GAT VKI S 519 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC2 / LC CKVSGYTFTDGHMHWVQQAPG ( 288 ) TITCRASQDINNYLNWYQQ2 KGLEWMGWIDPENGDLEYASK KPGKVPKLLI YYTSRLHSGFQGRVTITADTSTDTAYMELS VPSRFSGSGSGTDFTLTIS SLRSEDTAVYYCATSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 474 EVQL VQ S GAEVKK P GAT VKI S 521 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC3 / LC CKVSGFNIKDGHMHWVQQAPG ( 284 ) TITCRASQDINNYLAWYQQ1 KGLEWMGLIDPENGDLI YAEK KPGKVPKLLI YYTSTLQSGFQGRVTITADTSTDTAYMELS VPSRFSGSGSGTDFTLTIS SLRSEDTAVYYCTTSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 475 EVQL VQ S GAEVKK P GAT VKI S 519 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC4 / LC CTAS GFNI KDGHMHWVQQAPG ( 288 ) TITCRASQDINNYLNWYQQ2 KGLEWMGWIDPENGDLEYAEK KPGKVPKLLI YYTSRLHSGFQGRVTITADTSTDTAYMELS VPSRFSGSGSGTDFTLTIS SLRSEDTAVYYCTTSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 476 EVQL VQ S GAEVKK P GAT VKI S 522 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC5 / LC CKVSGFNIKDGHMHWVQQAPG TITCRASQDINNYLNWYQQ5 KGLEWIGWIDPENGDLEYASK KPGKVPKLLI YYTSRLHSGFQGRATLTADTSTDTAYMELS VPSRFSGSGSGTDYTLTIS SLRSEDTAVYYCTTSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 477 EVQLVESGGGLVQPGGSLRLS 523 DIQLTQSPSSLSASVGDRV WO 2025137236A1 HC6 / LC CAVSGFNIKDGHMHWIRQAPG TITCRASQDINNYLNWYQQ6 KGLE WVAW I D P EN GD LE YAS K KPGKAPKLLI YYTSRLHSGFQGRITISRDDSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCTTSRRGYFF SLQPEDFATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 478 QVQLVQSGAEVKKPGASVKVS 524 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC8 / LC CKASGYTFTDGHMHWVRQAPG ( 294 ) TITCRASQDINNYLNWYQQ4 QGLEWIGWIDPENGDLEYASK KPGKAPKLLI YYTSRLHSG FQGRVTLTRDTSSNTAYLELS VPSRFSGSGSGTDFTLTIS SLTSEDTAVYYCTTSRRGYFF SLQPEDFATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 479 QVQLVQSGAEVKKPGASVKVS 525 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC9 / LC CKASGFNIKDGHMHWVRQAPG TITCRASQDINNYLNWYQQ7 QGLEWIGWIDPENGDLEYASK KPGKAPKLLI YYTSRLHSG FQGRATLTADTSSNTAYLELS VPSRFSGSGSGTDYTLTIS SLTSEDTAVYYCTTSRRGYFF SLQPEDFATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 480 QVQLVQSGAEVKKPGASVKVS 524 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC10 / L CKASGFNIKDGYMHWVRQAPG ( 294 ) TITCRASQDINNYLNWYQQC7 QGLEWMGWIDPENGDTEYAQK KPGKAPKLLI YYTSRLHSG FQGRVTLTRDTSINTAYLELS VPSRFSGSGSGTDFTLTIS SLTSEDTAVYYCTTSRRGYFF SLQPEDFATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 481 QVQLVQSGAEVKKPGASVKVS 526 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC11 / L CKASGFNIKDGHMHWVRQAPG TITCRASQDINNYLNWYQQC8 QGLEWMGWIDPENGDLEYAQK KPGKAPKLLI YYTSSLQSG FQGRVTLTRDTSSNTAYLELS VPSRFSGSGSGTDFTLTIS SLTSEDTAVYYCTTSRRGYFF SLQPEDFATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 482 QVQLVQSGAEVKKPGASVKVS 524 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC12LC CTASGFNIKDGHMHWVRQAPG ( 294 ) TITCRASQDINNYLNWYQQ4 QGLEWMGWIDPENGDLEYAQK KPGKAPKLLI YYTSRLHSG FQGRVTLTRDTSSNTAYLELS VPSRFSGSGSGTDFTLTIS SLTSEDTAVYYCTTSRRGYFF SLQPEDFATYYCQQGNTLPDYWGQGTLVTVSS WTFGQGTKVEIKDB1 / 163717029.3 136Docket No. 133186-5032-WO1E12- 483 EVQLLESGGGLVQPGGSLRLS 519 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC13 / L CAASGFTFSDGHMHWVRQAPG ( 288 ) TITCRASQDINNYLNWYQQC2 KGLEWVSWIDPENGDLEYASK KPGKVPKLLI YYTSRLHSGFQGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCAKSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 484 EVQLLESGGGLVQPGGSLRLS 519 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC14 / L CAASGFNIKDGAMSWVRQAPG ( 288 ) TITCRASQDINNYLNWYQQC2 KGLEWVSAIDPENGDTYYADS KPGKVPKLLI YYTSRLHSGVKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCAKSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 485 EVQLLESGGGLVQPGGSLRLS 521 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC15 / L CAASGFNIKDGHMSWVRQAPG ( 284 ) TITCRASQDINNYLAWYQQCl KGLEWVSAIDPENGDLYYADS KPGKVPKLLI YYTSTLQSGVKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCTTSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK1E12- 486 EVQLLESGGGLVQPGGSLRLS 519 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC16 / L CTASGFNIKDGHMHWVRQAPG ( 288 ) TITCRASQDINNYLNWYQQC2 KGLEWVSWIDPENGDLEYADS KPGKVPKLLI YYTSRLHSGVKGRFTISRDNSKNTLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCTTSRRGYFF SLQPEDVATYYCQQGNTLP DYWGQGTLVTVSS WTFGQGTKVEIK5H4- 487 QVTLKESGPTLVKPTQTLTLT 527 DIVMTQTPLSLSVTPGQPA WO 2025137236A1 HC1 / LC CTFSGFSLSTFGVGVGWIRQP SISCRSSQTILHSDGNTYL3 PGKALEWLALIWWDDEKRYGP EWYLQKPGQSPQLLIYKVS SLKSRLTITKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCAHIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTMVTVS S GSHVPYTFGQGTKLEIK5H4- 488 QVTLKESGPTLVKPTQTLTLT 528 DWMTQTPLSLPVTLGQPA WO 2025137236A1 HC10 / L CSFSGFSLSTFGVGVGWIRQS ( 416) SISCRSSQTILHSDGNTYLC7 PGKALEWLALIWWDDEKYYNP YWYLQKPGQSPQLLIYKVS SLKTRLSISKDTSKNQVFLTM NRFSGVPDRFSGSGSGTDF TNVDPADTATYYCARIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 489 QVTLKESGPTLVKPTQTLTLT 529 DWMTQTPLSLPVTLGQPA WO 2025137236A1 HC12 / L CSFSGFSLSTFGVGVGWIRQS ( 413 ) SISCRSSQTILHSDGNTYLC6 PGKALEWLAHIWWDDEKYYNP EWYLQKPGQSPQLLIYKVS SLKTRLSISKDTSKNQVFLTM NRFSGVPDRFSGSGSGTDF TNVD PADTAT Y YCARI D S T W TLKISRVEAEDVGVYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 490 QVTLKESGPTLVKPTQTLTLT 529 DWMTQTPLSLPVTLGQPA WO 2025137236A1 HC13 / L CSFSGFSLSTFGVGVGWIRQS ( 413 ) SISCRSSQTILHSDGNTYLC6 PGKALEWLAHIWWDDEKYSNP EWYLQKPGQSPQLLIYKVS ALKTRLSISKDTSKNQVFLTM NRFSGVPDRFSGSGSGTDF TNVD PADTAT Y YCARI D S T W TLKISRVEAEDVGVYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 491 QVTLKESGPTLVKPTQTLTLT 530 DIVMTQTPLSLSVTPGQPA WO 2025137236A1 HC2 / LC CTFSGFSLSTFGVGVGWIRQP SISCKSSQTILHSDGNTYL6 PGKALEWLALIWWDDEKRYGP YWYLQKPGQSPQLLIYKVS SLKSRLTITKDTSKNQWLTM SRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTMVTVS S GSHVPYTFGQGTKLEIK5H4- 492 QVTLKESGPTLVKPTQTLTLT 531 DIVMTQTPLSLSVTPGQPA WO 2025137236A1 HC2 / LC CSFSGFSLSTFGVGVGWIRQP ( 404 ) SISCRSSQTILHSDGNTYL1 PGKALEWLAHIWWDDEKYYGP EWYLQKPGQSPQLLIYKVS SLKSRLTITKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTMVTVS S GSHVPYTFGQGTKLEIK5H4- 493 DI QMTQ S P S S L SAS VGDRVT I 531 DIVMTQTPLSLSVTPGQPA WO 2025137236A1 HC3 / LC TCRASQDINNYLNWYQQKPGK ( 404 ) SISCRSSQTILHSDGNTYL2 APKLLIYYTSRLHSGVPSRFS EWYLQKPGQSPQLLIYKVS GSGSGTDYTLTISSLQPEDFA NRFSGVPDRFSGSGSGTDF TYYCQQGNTLPWTFGQGTKVE TLKISRVEAEDVGVYYCFQ IK GSHVPYTFGQGTKLEIK5H4- 494 QVTLRESGPALVKPTQTLTLT 532 DIVMTQSPDSLSVSLGERA WO 2025137236A1 HC4 / LC CTVSGFSLSTFGVGVGWIRQP TINCRSSQTILHSDGNTYL2 PGKALEWLAHIWWDDEKYSNP EWYQQKPGQPPKLLIYKVSDB1 / 163717029.3 137Docket No. 133186-5032-WOALKTRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMD PVDTAT Y YCARI D S T W TLTISSLQAEDVAVYYCFQ AYAYWGQGS LVTVS S GS HVP YT FGGGT KVEI K5H4- 495 QVTLKESGPTLVKPTQTLTLT 529 DWMTQTPLSLPVTLGQPA WO 2025137236A1 HC7 / LC CSFSGFSLSTFGVGVGWIRQP ( 413 ) SISCRSSQTILHSDGNTYL9 PGKALEWLAHIWWDDEKYSNP EWYLQKPGQSPQLLIYKVS ALKTRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNVDPVDTATYYCARIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 496 QITLKESGPTLVKPTQTLTLT 525 DWMTQTPLSLPVTLGQPA WO 2025137236A1 HC8 / LC CTFSGFSLSTFGVGVGWIRQP ( 416) SISCRSSQTILHSDGNTYL6 PGKALEWLALIWWDDEKRYNP YWYLQKPGQSPQLLIYKVS SLKTRLTITKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNMDPVDTATYYCARIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 497 QVTLKESGPTLVKPTQTLTLT 529 DWMTQTPLSLPVTLGQPA WO 2025137236A1 HC14 / L CSFSGFSLSTFGVGVGWIRQP ( 413 ) SISCRSSQTILHSDGNTYLC7 PGKALEWLAHIWWDDEKYYNP EWYLQKPGQSPQLLIYKVS SLKTRLTISKDTSKNQWLTM NRFSGVPDRFSGSGSGTDF TNVDPVDTATYYCARIDSTWTLKISRVEAEDVGVYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 498 EVQLLESGGGLVQPGGSLRLS 533 D I VMT Q S P D S LAVS LGE RA WO 2025137236A1 HC15 / L CAASGFSLSTFGVSWVRQAPG TINCRSSQTILHSDGNTYLC6 KGLEWVSAIWWDDETYYADSV EWYQQKPGQPPKLLIYKVS KGRFTISRDNSKNTLYLQMNS NRFSGVPDRFSGSGSGTDF LRAEDTAVYYCAKIDSTWAYT L T I S S LQAE DVAV Y YC FQ AYWGQGTLVTVSS GS HVP YT FGGGT KVEI K5H4- 499 QVTLKESGPTLVKPTQTLTLT 534 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC9 / LC CSFSGFSLSTFGVGVGWIRQS ( 425 ) TITCRSSQTILHSDGNTYL8 PGKALEWLALIWWDDEKYYNP EWYQQKPGKAPKLLIYKVS SLKTRLSISKDTSKNQVFLTM NRFSGVPSRFSGSGSGTDF TNVD PADTATY YCARI D S T W TLTISSLQPEDFATYYCFQ AYAYWGQGTLVTVSS GSHVPYTFGQGTKLEIK5H4- 500 QVQL VQ S GAEVKK P G S S VKVS 535 DWMTQTPLSLSVTPGQPA WO 2025137236A1 HC10 / L ( 393 ) CS FS GFS L S T FGVGVGWVRQA SISCRSSQTILHSDGNTYLCI O PGQGLEWMGHIWWDDEKYYAQ EWYLQKPGQSPQLLIYKVS KFQGRVTITADESTSTAYMEL NRFSGVPDRFSGSGSGTDF SSLRSEDTAVYYCARIDSTW TLKISRVEAEDVGVYYCFQ AYAYWGQGTMVTVS S GSHVPYTFGQGTKLEIK5H4- 501 QVTLRESGPALVKPTQTLTLT 534 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC17 / L CTFSGFSLSTFGVGVGWIRQP ( 425 ) TITCRSSQTILHSDGNTYLC5 PGKALEWLAHIWWDDEKYSNP EWYQQKPGKAPKLLIYKVS ALKTRLTISKDTSKNQWLTM NRFSGVPSRFSGSGSGTDF TNMD PVDTAT Y YCARI D S T W TLTISSLQPEDFATYYCFQ AYAYWGQGS LVTVS S GSHVPYTFGQGTKLEIK5H4- 500 QVQL VQ S GAEVKK P G S S VKVS 534 DIQMTQSPSSLSASVGDRV WO 2025137236A1 HC6 / LC ( 393 ) CS FS GFS L S T FGVGVGWVRQA ( 425 ) TITCRSSQTILHSDGNTYL10 PGQGLEWMGHIWWDDEKYYAQ EWYQQKPGKAPKLLIYKVS KFQGRVTITADESTSTAYMEL NRFSGVPSRFSGSGSGTDF SSLRSEDTAVYYCARIDSTW TLTISSLQPEDFATYYCFQ AYAYWGQGTMVTVS S GSHVPYTFGQGTKLEIK1 502 EVQLVESGGGLVQPGGSLRLS 536 DIQMTQSPSSLSASVGDRV WO 2025149947CAASGFTFNSYGMSWVRQAPG TITCSVSSSVFYVHWYQQK KGLEWVAT I S S GGS YKYYVD S PGKAPKLLIYDTSKLASGV VKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTDFTFTISS S L RAED TAVY YCARH P D YDGV LQPEDIATYYCQQWNSNPP WFAYWGQGTLVTVSS TFGGGTKVEIK2 503 EVQLVESGGDLVKPGGSLKLS 537 QIVLTQSPAIMSASPGEKV WO 2025149947CAASGFTFNSYGMSWVRQTPD TMTCS VS S SVFYVHWYQQK KRLEWVATISSGGSYTYYPDS SGTSPKRWIYDTSKLASGV VKGRFT I S RDNAKNTLYLQMS PARFSGSGSGTSYSLTISS SLKSEDTAMYYCARHPDYDGV MEAEDAATYYCQQWNSNPP WFAYWGQGTLVTVSA TFGGGTKLEIK3 504 EVQLVQSGAEVKKPGASVKVS 538 EIVLTQSPATLSLSPGERA WO 2025149947CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ QGLEWMGIINPSGGSTSYAQK RPGQAPRLLIYDASNRATG FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDGVLRYF S LE P E D FAVY YC QQ RAN VFTFGQGTKVEIKDB1 / 163717029.3 138Docket No. 133186-5032-WODWLLDYYYYMDVWGKGTTVTVS34 505 EVQLVQSGAEVKKPGASVKVS 539 EIVMTQSPATLSLSPGERA WO 2025149947CKASGYTFTSYYMHWVRQAPG TLSCRASQSVGSYLAWYQQ QGLEWMGIINPSGGSTSYAQK KPGQAPRLLIYDASNRATG FQGRVTMTRDTSTSTVYMELS IPARFSGSGSGTDFTLTIS SLRSEDTAVYYCARDAELRHF SLQPEDFAVYYCQQRAQEF DHLLDYHYYMDVWGQGTTVTV TFGQGTKVEIK SS1 506 EVQLQQFGAELVKPGASVKIS 540 NIVMTQSPQSMSMSVGERV WO 2025085867CKASGYSFSDFNIEWLKQSHG TLSCKASENVGAYVSWFQQ Al KSLEWIGDINPNYDSTNYNQK KPDQSPKLLILAASNRYTG FKGRATLTVDKSSSTAYMEVR VPARFIGSGSATDFTLTIS SLTSEDTAVYYCARLGYGYAM SVQAEDLADYHCGQSYTYP DYWGQGTSVTVSS YTFGGGTKLEIKRADAAPT VS2 507 EVQLQQFGAELVKPGASVKIS 541 IVMTQSPQSMSMSVGERVT WO 2025085867CKASGYSFSDFNIEWLKQSHG LSCKASENVGAYVSWFQQK Al KSLEWIGDINPNYDSTNYNQK PDQSPKLLILAASNRYTGV FKGRATLTVDKSSSTAYMEVR PARFIGSGSATDFTLTISS SLTSEDTAVYYCARLGYGYAM VQAEDLADYHCGQS YTYPY DYWGQGTSVTVSSASTKGPSV TFGGGTKLEIKRADAAPTV FPLAPS SKSTS GGTAALGCLV SI FPPSDEQLKS GTASWC KDYFPEPVTVSWNSGALTSGV LLNNFYPREAKVQWKVDNA HTFPAVLQSSGLYSLSSWTV LQS GNSQE SVTEQD SKD S T PS SS LGTQTYI CNVNHKPSNT YSLSSTLTLSKADYEKHKV KVDKKVEPKSCDKTHTCPPCP YACEVTHQGLSS PVTKS FN APELLGGPSVFLFPPKPKDTL RGEC MI SRTPEVTCVVVDVSHEDPE VKFNWYVD GVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKT I SKAKGQPREPQVYTLPPSRE EMTKNQVS LTC LVKGFY PSD I AVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQ GNVFS C SVMHEALHNHY TQKS LSLSPGK9A2- 508 EVQLVESGGGLVQPGGSLRLS 542 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhuml CAASGFTFSDYGMHWVRQAPG TITCRASENI YS YLTWYQQ AlKGLEWVAYISSGSSIIYYVDS KPGKAPKFLVYNAKTLAEGVKGRFTISRDNAKNSLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCARGLDWYFD SLQPEDFATYYCQHHFGTP VWGQGTTVTVSS LTFGQGTKLEIK9A2- 508 EVQLVESGGGLVQPGGSLRLS 543 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhum2 CAASGFTFSDYGMHWVRQAPG TITCRASENI YS YLTWYQQ AlKGLEWVAYISSGSSIIYYVDS KQGKS PKFLVYNAKTLAEGVKGRFTISRDNAKNSLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCARGLDWYFD SLQPEDFATYYCQHHFGTP VWGQGTTVTVSS LTFGQGTKLEIK3A11- 509 EVQLVESGGGLVQPGGSLRLS 544 DIQLTQSPSFLSASVGDRV WO 2025199124 Vlhuml CAASGFTFSSYAMSWVRQAPG TMTCRAS S S VI YMHWYQQK Al KGLEWVATISSGGIYTYYVDS PGKAPKRWIYDTSKLASGV VKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTEYTLTISS SLRAEDTAVYYCAIHEDYDSV MQPEDAATYYCQQWTGNPL GMDFWGQGTTVTVSS TFGQGTKLEIK3A11- 509 EVQLVESGGGLVQPGGSLRLS 545 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhum2 CAASGFTFSSYAMSWVRQAPG TMTCRAS S S VI YMHWYQQK Al KGLEWVATISSGGIYTYYVDS PGKAPKRWIYDTSKLASGV VKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTEFTLTISS SLRAEDTAVYYCAIHEDYDSV LQPEDFATYYCQQWTGNPL GMDFWGQGTTVTVSS TFGQGTKLEIKDB1 / 163717029.3 139Docket No. 133186-5032-WO3A11- 509 EVQLVESGGGLVQPGGSLRLS 546 EIVLTQSPGTLSLSPGERA WO 2025199124 VLhum3 CAASGFTFSSYAMSWVRQAPG TLSCRASSSVIYMHWYQQK Al KGLEWVATISSGGIYTYYVDS SGQAPRRWIYDTSKLASGI VKGRFTISRDNAKNSLYLQMN PDRFSGSGSGTDFTLTISR SLRAEDTAVYYCAIHEDYDSV LEPEDAAVYYCQQWTGNPL GMDFWGQGTTVTVSS TFGQGTKLEIK6662- 510 QVQLVQSGAEVKKPGSSVKVS 547 DIQMTQSPSSLSASVGDRV WO 2025199124 VHhuml CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKVPKLLISGATSLEIG VLhuml FQGRATFTADESTSTAYMELS VPSRFSGSGSGTDFTLTIS SLRSEDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSP FDVWGQGTTVTVSS PTFGQGTKLEIK6662- 510 QVQLVQSGAEVKKPGSSVKVS 548 DIQMTQSPSSFSASVGDRV WO 2025199124 VHhuml CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKAPKLLISGATSLEIG VLhum2 FQGRATFTADESTSTAYMELS VPSRFSGSGSGTDYTLTIS SLRSEDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSP FDVWGQGTTVTVSS PTFGQGTKLEIK6662- 511 QVQLVQSGAEVKKPGASVKVS 547 DIQMTQSPSSLSASVGDRV WO 2025199124 VHhum2 CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKVPKLLISGATSLEIG VLhuml FQGRATMTADTSISTAYMELS VPSRFSGSGSGTDFTLTIS RLRSDDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSP FDVWGQGTTVTVSS PTFGQGTKLEIK6662- 511 QVQLVQSGAEVKKPGASVKVS 548 DIQMTQSPSSFSASVGDRV WO 2025199124 VHhum2 CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKAPKLLISGATSLEIG VLhum2 FQGRATMTADTSISTAYMELS VPSRFSGSGSGTDYTLTIS RLRSDDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSP FDVWGQGTTVTVSS PTFGQGTKLEIK9A2- 512 EVQLVESGGGLVQPGGSLRLS 549 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhuml CAASGFTFSDYGMHWVRQAPG TITCRASENI YS YLTWYQQ Al-IgGl- KGLEWVAYISSGSSIIYYVDS KPGKAPKFLVYNAKTLAEGF405L VKGRFTISRDNAKNSLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCARGLDWYFD SLQPEDFATYYCQHHFGTP VWGQGTTVTVS SASTKGPSVF LTFGQGTKLEIKRTVAAPS PLAPSSKSTSGGTAALGCLVK VFIFPPSDEQLKSGTASW DYFPEPVTVSWNSGALTSGVH CLLNNFYPREAKVQWKVDN TFPAVLQS SGLYS LS SWTVP ALQSGNSQESVTEQDSKDS SSSLGTQTYICNVNHKPSNTK TYSLSSTLTLSKADYEKHK VDKKVEPKSCDKTHTCPPCPA VYACEVTHQGLS S PVTKS F PELLGGPSVFLFPPKPKDTLM NRGEC I SRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREE QYNS TYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLD SDGSFLLYSKLTVDKSRWQQG NVFS CSVMHEALHNHYTQKS L SLSPGK9A2- 512 EVQLVESGGGLVQPGGSLRLS 550 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhum2 CAASGFTFSDYGMHWVRQAPG TITCRASENI YS YLTWYQQ Al-IgGl- KGLEWVAYISSGSSIIYYVDS KQGKS PKFLVYNAKTLAEGF405L VKGRFTISRDNAKNSLYLQMN VPSRFSGSGSGTDFTLTIS SLRAEDTAVYYCARGLDWYFD SLQPEDFATYYCQHHFGTP VWGQGTTVTVS SASTKGPSVF LTFGQGTKLEIKRTVAAPS PLAPSSKSTSGGTAALGCLVK VFIFPPSDEQLKSGTASW DYFPEPVTVSWNSGALTSGVH CLLNNFYPREAKVQWKVDN TFPAVLQS SGLYS LS SWTVP ALQSGNSQESVTEQDSKDS SSSLGTQTYICNVNHKPSNTK TYSLSSTLTLSKADYEKHK VDKKVEPKSCDKTHTCPPCPA VYACEVTHQGLS S PVTKS FPELLGGPSVFLFPPKPKDTLM NRGECDB1 / 163717029.3 140Docket No. 133186-5032-WOISRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREE QYNS TYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLD SDGSFLLYSKLTVDKSRWQQG NVFS CSVMHEALHNHYTQKS L SLSPGK3A11- 513 EVQLVESGGGLVQPGGSLRLS 551 DIQLTQSPSFLSASVGDRV WO 2025199124 Vlhuml CAASGFTFSSYAMSWVRQAPG TMTCRAS S S VI YMHWYQQK Al-IgGl- KGLEWVATISSGGIYTYYVDS PGKAPKRWIYDTSKLASGVF405L VKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTEYTLTISS SLRAEDTAVYYCAIHEDYDSV MQPEDAATYYCQQWTGNPL GMDFWGQGTTVTVSSASTKGP TFGQGTKLEIKRTVAAPSV SVFPLAPS SKS TS GGTAALGC FI FPPSDEQLKS GTASWC LVKDYFPEPVTVSWNSGALTS LLNNFYPREAKVQWKVDNA GVHTFPAVLQS S GLY S LS S W LQSGNSQESVTEQDSKDST TVPS SS LGTQTYI CNVNHKPS YS LSS TLTLSKADYEKHKV NTKVDKKVEPKSCDKTHTCPP YACEVTHQGLSS PVTKS FN CPAPELLGGPSVFLFPPKPKD RGEC TLMI SRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIE KTI SKAKGQPREPQVYTLPPS RDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPP VLDSDGSFLLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQ KSLSLSPGK3A11- 513 EVQLVESGGGLVQPGGSLRLS 552 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhum2 CAASGFTFSSYAMSWVRQAPG TMTCRAS S S VI YMHWYQQK Al-IgGl- KGLEWVATISSGGIYTYYVDS PGKAPKRWIYDTSKLASGVF405L VKGRFTISRDNAKNSLYLQMN PSRFSGSGSGTEFTLTISS SLRAEDTAVYYCAIHEDYDSV LQPEDFATYYCQQWTGNPL GMDFWGQGTTVTVSSASTKGP TFGQGTKLEIKRTVAAPSV SVFPLAPS SKS TS GGTAALGC FI FPPSDEQLKS GTASWC LVKDYFPEPVTVSWNSGALTS LLNNFYPREAKVQWKVDNA GVHTFPAVLQS S GLY S LS SW LQSGNSQESVTEQDSKDST TVPS SS LGTQTYI CNVNHKPS YS LSS TLTLSKADYEKHKV NTKVDKKVEPKSCDKTHTCPP YACEVTHQGLSS PVTKS FN CPAPELLGGPSVFLFPPKPKD RGEC TLMI SRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIE KTI SKAKGQPREPQVYTLPPS RDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPP VLDSDGSFLLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQ KSLSLSPGK3A11- 513 EVQLVESGGGLVQPGGSLRLS 553 EIVLTQSPGTLSLSPGERA WO 2025199124 VLhum3 CAASGFTFSSYAMSWVRQAPG TLSCRASSSVI YMHWYQQK Al-IgGl- KGLEWVATISSGGIYTYYVDS SGQAPRRWIYDTSKLASGIF405L VKGRFTISRDNAKNSLYLQMN PDRFSGSGSGTDFTLTISR SLRAEDTAVYYCAIHEDYDSV LEPEDAAVYYCQQWTGNPL GMDFWGQGTTVTVSSASTKGP TFGQGTKLEIKRTVAAPSV SVFPLAPS SKS TS GGTAALGC FI FPPSDEQLKS GTASWC LVKDYFPEPVTVSWNSGALTS LLNNFYPREAKVQWKVDNA GVHTFPAVLQS S GLY S LS S W LQSGNSQESVTEQDSKDST TVPS SS LGTQTYI CNVNHKPS YS LSS TLTLSKADYEKHKV NTKVDKKVEPKSCDKTHTCPP YACEVTHQGLSS PVTKS FN CPAPELLGGPSVFLFPPKPKD RGEC TLMI SRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSDB1 / 163717029.3 141Docket No. 133186-5032-WORDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPP VLDSDGSFLLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQ KSLSLSPGK6662- 514 QVQLVQSGAEVKKPGSSVKVS 554 DIQMTQSPSSLSASVGDRV WO 2025199124 VHhuml CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKVPKLLISGATSLEIG VLhuml FQGRATFTADESTSTAYMELS VPSRFSGSGSGTDFTLTIS-IgGl- SLRSEDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSPF405L FDVWGQGTTVTVS SASTKGPS P T FGQ GT KLE I KRTVAAPS VFPLAPSSKSTSGGTAALGCL VFIFPPSDEQLKSGTASW VKDYFPEPVTVSWNSGALTSG CLLNNFYPREAKVQWKVDN VHTFPAVLQSS GLYS LS SWT ALQSGNSQESVTEQDSKDS VPS S S LGTQTY I CNVNHKPSN TYSLSSTLTLSKADYEKHK TKVDKKVEPKSCDKTHTCPPC VYACEVTHQGLS S PVTKS F PAPELLGGPSVFLFPPKPKDT NRGEC LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TI SKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPV LDSDGSFLLYSKLTVDKSRWQ QGNVFS CSVMHEALHNHYTQK SLSLSPGK6662- 514 QVQLVQSGAEVKKPGSSVKVS 555 DIQMTQSPSSFSASVGDRV WO 2025199124 VHhuml CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKAPKLLISGATSLEIG VLhum2 FQGRATFTADESTSTAYMELS VPSRFSGSGSGTDYTLTIS-IgGl- SLRSEDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSPF405L FDVWGQGTTVTVS SASTKGPS P T FGQ GT KLE I KRTVAAPS VFPLAPSSKSTSGGTAALGCL VFIFPPSDEQLKSGTASW VKDYFPEPVTVSWNS GALTS G CLLNNFYPREAKVQWKVDN VHTFPAVLQSS GLYS LS SWT ALQSGNSQESVTEQDSKDS VPS S S LGTQTY I CNVNHKPSN TYSLSSTLTLSKADYEKHK TKVDKKVEPKSCDKTHTCPPC VYACEVTHQGLS S PVTKS F PAPELLGGPSVFLFPPKPKDT NRGEC LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TI SKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPV LDSDGSFLLYSKLTVDKSRWQ QGNVFS CSVMHEALHNHYTQK SLSLSPGK6662- 515 QVQLVQSGAEVKKPGASVKVS 554 DIQMTQSPSSLSASVGDRV WO 2025199124 VHhum2 CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKVPKLLISGATSLEIG VLhuml FQGRATMTADTSISTAYMELS VPSRFSGSGSGTDFTLTIS-IgGl- RLRSDDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSPF405L FDVWGQGTTVTVS SASTKGPS P T FGQ GT KLE I KRTVAAPS VFPLAPSSKSTSGGTAALGCL VFIFPPSDEQLKSGTASW VKDYFPEPVTVSWNS GALTS G CLLNNFYPREAKVQWKVDN VHTFPAVLQSS GLYS LS SWT ALQSGNSQESVTEQDSKDS VPS S S LGTQTY I CNVNHKPSN TYSLSSTLTLSKADYEKHK TKVDKKVEPKSCDKTHTCPPC VYACEVTHQGLS S PVTKS F PAPELLGGPSVFLFPPKPKDT NRGEC LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TI SKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSRWQDB1 / 163717029.3 142Docket No. 133186-5032-WOQGNVFS CSVMHEALHNHYTQK SLSLSPGK6662- 515 QVQLVQSGAEVKKPGASVKVS 555 DIQMTQSPSSFSASVGDRV WO 2025199124 VHhum2 CKASGYTLSNYWIEWVRQAPG TITCRASEDI YYRLAWYQQ Al QGLEWIGEILPGSGSTNYAQK KPGKAPKLLISGATSLEIG VLhum2 FQGRATMTADTSISTAYMELS VPSRFSGSGSGTDYTLTIS-IgGl- RLRSDDTAVYYCARVAGYDWY SLQPEDVATYYCQHYWSSPF405L FDVWGQGTTVTVS SASTKGPS P T FGQ GT KLE I KRTVAAPS VFPLAPSSKSTSGGTAALGCL VFIFPPSDEQLKSGTASW VKDYFPEPVTVSWNSGALTSG CLLNNFYPREAKVQWKVDN VHTFPAVLQSS GLYS LS SWT ALQSGNSQESVTEQDSKDS VPS S S LGTQTY I CNVNHKPSN TYSLSSTLTLSKADYEKHK TKVDKKVEPKSCDKTHTCPPC VYACEVTHQGLS S PVTKS F PAPELLGGPSVFLFPPKPKDT NRGEC LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPV LDSDGSFLLYSKLTVDKSRWQ QGNVFS CSVMHEALHNHYTQK SLSLSPGK9A2- 516 EVQLVESGGGLVQPGGSLRLS 549 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhuml CAASGFTFSDYGMHWVRQAPG TITCRASENI YS YLTWYQQ Al-IgGl- KGLEWVAYISSGSSIIYYVDS KPGKAPKFLVYNAKTLAEGL234A / VKGRFTISRDNAKNSLYLQMN VPSRFSGSGSGTDFTLTISL235A / SLRAEDTAVYYCARGLDWYFD SLQPEDFATYYCQHHFGTPF405L VWGQGTTVTVS SASTKGPSVF LTFGQGTKLEIKRTVAAPS PLAPSSKSTSGGTAALGCLVK VFIFPPSDEQLKSGTASW DYFPEPVTVSWNSGALTSGVH CLLNNFYPREAKVQWKVDN TFPAVLQS SGLYS LS SWTVP ALQSGNSQESVTEQDSKDS SSSLGTQTYICNVNHKPSNTK TYSLSSTLTLSKADYEKHK VDKKVEPKSCDKTHTCPPCPA VYACEVTHQGLS S PVTKS F PEAAGGPSVFLFPPKPKDTLM NRGEC I SRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREE QYNS TYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLD SDGSFLLYSKLTVDKSRWQQG NVFS CSVMHEALHNHYTQKS L SLSPGK3A11- 517 EVQLVESGGGLVQPGGSLRLS 552 DIQMTQSPSSLSASVGDRV WO 2025199124 VLhuml CAASGFTFSSYAMSWVRQAPG TITCRASENI YS YLTWYQQ Al-IgGl- KGLEWVATISSGGIYTYYVDS KQGKS PKFLVYNAKTLAEGL234A / VKGRFTISRDNAKNSLYLQMN VPSRFSGSGSGTDFTLTISL235A / SLRAEDTAVYYCAIHEDYDSV SLQPEDFATYYCQHHFGTPF405L GMDFWGQGTTVTVSSASTKGP LTFGQGTKLEIKRTVAAPSSVFPLAPS SKS TS GGTAALGC VFIFPPSDEQLKSGTASW LVKDYFPEPVTVSWNSGALTS CLLNNFYPREAKVQWKVDN GVHTFPAVLQS S GLY S LS S W ALQSGNSQESVTEQDSKDS TVPS SS LGTQTYI CNVNHKPS TYSLSSTLTLSKADYEKHK NTKVDKKVEPKSCDKTHTCPP VYACEVTHQGLS S PVTKS F CPAPEAAGGPSVFLFPPKPKD NRGEC TLMI SRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIE KTI SKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSRWDB1 / 163717029.3 143Docket No. 133186-5032-WO QQGNVFSCSVMHEALHNHYTQ KSLSLSPGK6662- 518 QVQLVQSGAEVKKPGSSVKVS 554 DIQLTQSPSFLSASVGDRV WO 2025199124 VLhuml CKASGYTLSNYWIEWVRQAPG TMTCRAS S S VI YMHWYQQK Al-IgGl- QGLEWIGEILPGSGSTNYAQK PGKAPKRWIYDTSKLASGVL234A / FQGRATFTADESTSTAYMELS PSRFSGSGSGTEYTLTISSL235A / SLRSEDTAVYYCARVAGYDWY MQPEDAATYYCQQWTGNPLF405L FDVWGQGTTVTVS SASTKGPS TFGQGTKLEIKRTVAAPSV VFPLAPSSKSTSGGTAALGCL FI FPPSDEQLKS GTASWC VKDYFPEPVTVSWNSGALTSG LLNNFYPREAKVQWKVDNA VHTFPAVLQSS GLYS LS SWT LQSGNSQESVTEQDSKDST VPS S S LGTQTY I CNVNHKPSN YS LSS TLTLSKADYEKHKV TKVDKKVEPKSCDKTHTCPPC YACEVTHQGLSS PVTKS FN PAPEAAGGPSVFLFPPKPKDT RGEC LMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPR EEQYNS TYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPV LDSDGSFLLYSKLTVDKSRWQ QGNVFS CSVMHEALHNHYTQKSLSLSPGK

[0246] Several human, humanized, and chimeric anti-CDCP 1 antibodies are disclosed in the patent literature (see, e.g., Table 3 above depicting the heavy chain, heavy chain variable region, light chain, and / or light chain variable regions of such antibodies. Such sequences can be found, for example, in Japanese Application Publication No. JP 2007 / 112734; PCT Application Publication Nos. WO 2022 / 212876, WO 2023 / 246701 Al, WO 2024 / 127366 Al, WO 2024 / 090927 Al; as well as U. S. Application Publication Nos. US 2023 / 0050380 Al, US 2022 / 0389113 Al, US 2022 / 011954 Al, US 2008 / 0008719 Al, US 2023 / 0265206 Al, US 2024 / 0026031 Al, US 2024 / 0123080 Al, US 2024 / 0084030 Al; and U. S. Patent No. 9,346,886, which are herein incorporated by reference in their entireties.

[0247] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH (or heavy chain variable region) that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 and / or a VE (or light chain variable region) that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555. In someDB1 / 163717029.3 144Docket No. 133186-5032-WOembodiments, the antibody or antigen binding fragment thereof comprises a VH (or heavy chain variable region) that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 and / or a VL (or light chain variable region) that comprises an amino acid sequence at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555.

[0248] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 and / or a VL that comprises an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555.

[0249] In some embodiments, the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least abo...

Claims

Docket No. 133186-5032-WOWE HEREBY CLAIM:

1. An antibody-drug conjugate (ADC) of formula (I):Ab-[L–D]nformula (I) pIZwherein in formula (I): )O=Ab is an antibody or antigen binding fragment thereof that binds to CUB Domain- Containing Protein-1 (CDCP1);L is a bond or a linker; )o=D is a drug moiety comprising an auristatin; and\ / Q— / n is an integer from 1 to 20.z <—o / / =IZ '2. The antibody-drug conjugate of claim 1, wherein the auristatin is selected from auristatin \ )o=E or an analogue thereof, auristatin F or an analogue thereof, monomethyl auristatin E (MMAE) or an analogue thereof, monomethyl auristatin F (MMAF) or an analogue thereof, dolastatin 10 or an analogue thereof, monomethyl auristatin D (MMAD) or an analogue thereof, auristatin PE or an analogue thereof, auristatin PYE or an analogue thereof, PF-06380101 or an analogue thereof, symplostatin 1 or an analogue thereof, symplostatin 3 or an analogue thereof, dolastatin H or an analogue thereof, and isodolastatin H or an analogue thereof.

3. The antibody-drug conjugate of claim 1 or 2, wherein D is selected from any one of formula 1001-1157:Formula No. Structure10011O1O 01002DBl / 163717029.3 184Docket No. 133186-5032-WOFormula No. Structure1003 y.SV o,. 9.\ A A A A. N— 9. N. J ANn;Ni^ n n i °x1 0 1 °\ O °x o. J o1004 I? i-NA" rNA YNY'r"? "nA1 0 1 O\ 0 O\ o *H. j 01005 H || I H\ A., A -N— Y A\. N.Nn »Nn Y^ n \ <1 0 1 ox0 0 *'Y^ H || IH? \ A A A < A J. A A1006nn;Nn n; °x1 0 1 O\ O O\ 0I? * 1 Ih? \ A A J. A A1007nn 'N9T n jf nN x1 O 1 O\ O O\ O AAAH || I H ||1008Nn ‘Nn n = / 1 O 1 O\ O O\ O AM / h? ** 1 ^7!h1009 A A A << < J.y y Ar ^Y Y n:N1 O 1 O\ O O\ OMDB1 / 163717029.3 185Docket No. 133186-5032-WO Formula No. Structure, Y H? V Q 1 H J1010° A\ ° 0^ 0u1011° °\ ° 0^ 0u1012 / YH2 O IH2 fT20O\ 0 O\ 01013 z Yh2 O Ih2 iYrN^IT T Y i H1014° AA °\0°\0 1^A\ A010150 1O\ O O^ 01010161O1O\ O O\ O10DB1 / 163717029.3 186Docket No. 133186-5032-WOFormula No. Structurei o1017 / Yh? i o ihi NZA A A _N— A A > A AA N; N n1 O ^A 1 O\ O O\ O0H ft 1 H ft X 1 -ANA.018 A NAA" Y TA N^^ON1 O ^A 1 °\ O O\ O A JAAA / A ^hA A ii < T\ / \ Z ^NA7 A Ih? x\ x\1019ZN y ANi Y Yf n; N OH1 O / A 1 O\ O O\ O AA^SM1020o y \ / H ft I HA A A / \ ^NA A ^NXAK / 1021z Nn inif n Yr n;NH 01 O\ 0 °x OMy \ / H ft I O I H ft A1022 A A AY A\NAN1 0AA1°\ 0 °\ 0uA y. A / HN. A?k*A* | / \Z^NA7 A I / NH. A? „z1023ZN Y ANYf Y K01 O / A 1 O\ 0 O\ 0uDB1 / 163717029.3 187Docket No. 133186-5032-WO Formula No. Structure1024 / Yhu i O i H fi1fT • f 1 Y|° Z\1O 0^ 0 *XX H || I H ||N y yNi^ n n; OH1 o = 1 O\ O O\ o1025 I JN. A AA ^yU\IHXX H || I H ||N y ■Njf n n; °1 O = 1 O\ O O\ oI J1026N\^Y 1 H o II A \ A f I I H o ||N Y:Njf n 0;OH1 ° = 1 oxo o^ o AAA1027 F-< I JN\^^yU\IHDB1 / 163717029.3 188Docket No. 133186-5032-WODB1 / 163717029.3 189Docket No. 133186-5032-WODB1 / 163717029.3 190Docket No. 133186-5032-WOFormula No. StructureY H 5 I O! H 9H10371O -1O o1HlXYYh? Yr fY I H 91038 f If i f i^T i if i YY1O =1O O^ O *YHs Y < Y i H?H1039 Y1O Y =1'Y oxO W O^ O Y* YHNYr^h? Yf rY i H?1040 f1if i Y * Y i ff Y y Y0 =10^ 0 O\ 01< XHXYNH0O }TN11041NY H S Y Y) I H 9N^Y YNVY T Y ioh° °\0°\ o X^,YjDB1 / 163717029.3 191Docket No. 133186-5032-WODB1 / 163717029.3 192Docket No. 133186-5032-WOFormula No. Structurey YY H j| I H1047 A X. / A A.. N— k. N.' N y YNn YY Yf Y i1 0 A^ 1 0. 0 0. 0 8 YA\ / PO3Na2IZ)o=1048 Y z —! / Q“ / ^'O=\ V-zZT\ AoO= / 104 z * — \ / Q— / 9z <—o4,'° — \ / IZ 'o=\Y^ \ )o=— \ ZH 9 YY I H 91050xN\N / N\^NV rN / N^°yA " 1 ~ o 1 o^ o O\ oo=\ ZIYf^ H 9 * ] YY!HH \1051 N Nr Y N Y n Y nNz> A1 O A\ ' O\ O O\ O='X|X'H / / \ \H I? * ] j H I?1052 -NYrN^NA^rNArAYN^1 0 1 °\ 0 °\ °=\|s\-NY¥HN^ 9N*A* ] ^ NXrX i¥HNvA 9 / 1053 1 O 1 O\ 0 O\ 0 AAST NHo1054 A / hA? * <*rk / \ ^ ^N—Y Y Y i\ ^hN. A?\z Nn:Nn n ^ Yi i1 O 1 0^ 0 0^ 0 YADB1 / 163717029.3 193Docket No. 133186-5032-WOFormula No. Structure1055 X i JJH? 1 ' V IHI*1 Ok 1AX O X O\ O AXJ<□ C. X1056? _zN JJ Yh;? hNnr j^ fl JJ i nh;? >01 0 X^ 1 0^ 0 0^ 0u\ / S Ok10 i 9.5 nr J \ > i w k xOH N7FN [T N jf [T jT / \ o1 0 1 0^ 0 0\ O i0KJ1058bN^-N. H Y H X 9 <k | ^\ ^ ON— k / 1k^ HN. X flNY;NT U 79 °H0'0' °\ 0 O\ 0Hb0i\-Y? H Y H? Y I H 1059 r0 H0 1 O X ' 0^ 0 0^ 0 k -!\| NHBDB1 / 163717029.3 194Docket No. 133186-5032-WODB1 / 163717029.3 195Docket No. 133186-5032-WO Formula No. Structure7 Y H? J O 1 H T2zN Y YNAA;106601 O 1 O\ O O \ ^\V NHo1067 A. A / N.. NA A, N. AfN Y;NY n;01 O A\ ' °\ O °x O Ax=\V NHo\ / K / / X k,0 X I Hn 9 \ ' > / II Hn y1068 X / °\^X^k, A / N. Xk,«A ^X / N— \ A. N. A=x\ rNn;Njk n n; °o 1 o 1 °\ O °\ OM X X N J / x k.0nr H 9 \ > iHy1069 A. A / N. / ^.,<\ / X / NA A, N. A,zN Y;Njl n n;01 O A\ 1 °\ O O\ Ou. j o1070 H 9 \ 7 I H Jf °Y^NY A Y YNT YY A yO 1 O Ax 1 °x O °x O X / Az x J oAAHo Y> i H1071 Y^NYNA Y YNY YYyO 1 O A\ 1 °\ 0 °x ° ksDB1 / 163717029.3 196Docket No. 133186-5032-WO Formula No. StructurekkH? 1 k' / IHnNx) — / > 1072V° ' ° ' °\ 0 O\ 0" Y^ H 9 kY 1 H H't) — / =\ 10730*)^ 1^NA'NYNYV Y YNYY^k V° '0Y\ ' 0^ 0 0^ 0k:>y i o^Y^ H 9 \ 7 I H1074X ° / YO ^N1\ ON^N 1V 0. r0NV 0. Y0NT Y^\\ o Y o T H Y J YY H 9 * 1 Y> I HO>^\ / x A X A A. Y A, NV,.vk1075yONiT1 0N[T [T' °\ 0 0\ ° 1 A;0xf ro1076H 9 * T I H ^kI nHNk' / i n 2. -Y / \ Y', »Y / N—107 N >< YNi^ n \ jf Y\ n / N; Y- 7 °V° 10^Y 1 °\ o °\ o X Y Y^Y\ NHoDB1 / 163717029.3 197Docket No. 133186-5032-WO Formula No. Structurei Q1078 YYH? i iA A -N— AZHNK ^ )Yv'Nn;Ni^ n YY n i \ ii yNH 1 0 1 0^ 0 0^ 0i o1079 YY H 9 YY i H YY °^^NAYNYXN-VV TYY YY “J™ 1 0 1 0^ 0 0^ 0 YYAY. j o1080A / M YYh? T ' V ihYrNA ] / TN—; ^M N^^ J ^ []NA jA [ / TNK / y ll1 0 1 0 0^ 0. j oYY H 9 nr i H1081 Y YNYyNH 1 O 1 0\ 0 0\ 0. j oYY H 9 Yr ( / i H Yr1082oy^N\N'YN;YYN-~L~ 1 o 1 o YY oNYi QA? YYhA II YY ^\ / YN—Y A I. N HKY JY1083 ' N y; N' Y n n i1 O ' °\ O °\ O Y-DB1 / 163717029.3 198Docket No. 133186-5032-WO Formula No. Structure1084VNH0Y\ O\ 0 °1085""L~1010^ 0 0^ 0u. v H1086? V O ihfui0zY °\ 0 °\ 0 ^Y^u1087VNH° Y\ 0^ 0 0^ 0 ^Y^vu1088~-L~-1O1O\ O O\ oTJ1089 A / N Y\hNY? / VVY ONV i HTNY r-YV-OW0YY 0\ 0 0\ 0u1090VNH' ° / Y 1 0\ 0 °\ 0VDB1 / 163717029.3 199Docket No. 133186-5032-WOFormula No. Structure10911 \ Qz— / 1 / YhI?092 AY\o=\ ^7 iA «AhY YA YY1o \1o. o ex oA Y>0A o0AAz / —Y IY Hn 9 * T '° — \ / ' / II Hn. N— AAA. A, 1093 i ^ N [T No=\ [T [T o yNH 1 0 ' °\0\"- Z °\ ° io— ^o=\ 0Y O ziH? T I H / =\ \ o — / xH1094Nn >Nn n A ( ' —\ / / 0"-L- I o i °\0°\ ° i 0 3 / " YI " Hn 9 * T ' / II HnAk, -A / N. A „,zA N— \ A / N.. A1095FN [T Y^ N jT jT / \ o1 o / Y 1 o^ o < A o i0H I? i H o’ A zN^ A A J. N. A1096Nn ‘Nn nNH2VNH101 O\ O O\ OvMDB1 / 163717029.3 200Docket No. 133186-5032-WOFormula No. StructureH I? | H I?1097 y N y TNn;NH2Y 1 0 A\ 1 oxo 0^ 0u1098 k oAA^ H 9 * T I H ^H2 AZN. A.. A, N— k / k AxN Y;Njk n kA n Y10990Y 1 o ^A 1 oxo o^ o A^\Y NHo|H|HY H J | O I H1100OH OH 1 O ^A 1 O\ O O\ Of' ro - M OH OH YH; Y 0 iHn> 1101 kA N Y YnkA n kA n YNOH OH 1 O A\ ' °\ O °\ O YA.YJ> \ H fl T O! H? A1102 | II - | A II A II -0o °\ o YA,MDB1 / 163717029.3 201Docket No. 133186-5032-WOFormula No. Structure1103 Yhi i O if if X T 100O\ O O\ OMA. Y -A ^HN. A s? V A1k> A i,c. x?x 1104HY X T i °° Y\ °\ ° °\ ° YAu1105. YH9 Y1O i k0 / \ O\ O O\ 0 AA110610 °\ 0 °\ 01107101O\ 0 O\ 01108101O\ 0 O\ 01109k^0 R / f1Y O\Y O ^^ OJ\Y 0 °'m kQYADB1 / 163717029.3 202Docket No. 133186-5032-WO Formula No. Structure1110 Y1° / Y10-A 0 °-V ° mm i0 10 0^ 0 %111217 Y H FT T O i H n1113 VV0'Y YY YVXO\ O O\ 0M7HH O 1 H n11140°\ o °\ ou7 1 H S Y O 1 H n1115AA0 NY^^XNV YNYN°\ 0 0^ 01116° 0^ 0 0^ 0uDB1 / 163717029.3 203Docket No. 133186-5032-WOFormula No. Structure7 OhH i O i H n1117 Y i s f i Y X T iNo °\ ° o^ ou1 \ Z H? T O I H1118 YX oYYT °\Y °A o^Yo W1119~4™ o10\ 0 0\ 0MXX H? I O 1 H n1120 YX YA YA Y'A11210°\ o °\ oi / N'X4 -p" M1122 I H 9 I H YxH,NY AN\Nk<NXYN^... I0>-^i S A1Si / N> ZS0. >s1123 / Y " i T H YXi 5 x i x SDB1 / 163717029.3 204Docket No. 133186-5032-WO Formula No. Structure11240 / \ / °0U O '1125i 5 A1 / J SA >HH? Y I1126° A""- ' °1127 oX w wo YY 1 o oxoU H YA >HHS? Y I o i H n> 11280 1O 0u1129Y H H V 6 1 "NA T f T Y Y ¥0O\ 0 °X 0 WI QH1130 / YH5 i 6 i Ho1O\ O O^ O1131, Y H 2 Y1O I H YY^ i o10\ 0 0\ 0DB1 / 163717029.3 205Docket No. 133186-5032-WOFormula No. Structure1132 Y H? Y I H f0O\ 0 01 OH1133 / YHs Y d iHio1O\ O 01134, YHu V d i " io1ox0 0^ 01135 z YHjY A IH° 0^ 0 0^ 0 YA1136, YH 6 I "AA0ArY A 'YYA 0\ o °\ o \A| OH1137 A / YVHU Y A 10AA O^\ 0Y H0\V 0 ^ \^Y1138 V H § V A I Ho10\ 0 0\ 0 YA1139A7A Y H N 1 O I H0NAT^NAAN^A fYY °\ o °\ oF^AADB1 / 163717029.3 206Docket No. 133186-5032-WOFormula No. Structure1 QH1140 / YH; Y O IHfo Ox0 0^ 01141A Y H° / A > » f VY 6 [ " 1°\Y O Y 0^Y0 " Ap^AAAl1142A °Y Z\X 0A^ 0Y 0^V0 A zAQA-1143A0Y / AX OA\ 0Y O\V O Y zkYAF1144 'Y vvHJY 0 ihjfH0YY °IA\0NY °\V0^ / n\AF1 QH11450AA °\ 0 °\ 0 ZAA- 1 ^NH1146T Y AHu 1! H0z YAfA O\ Or Y 0\Y f0FYYDB1 / 163717029.3 207Docket No. 133186-5032-WOFormula No. StructureI NH21147 7 Y H 5 Y < 7 I H fo10 O\ 0I ^NH1148 YHS 1 6 I H f1o10. 0 0. 0 A A1 NH21149 7 Y H H 1 O I H f AV o ^1^ 0^ 0NAV^A 0^ 01150 Y H! Y < 7 I H fo10 0\ 01 HlA1151 7 Y H J I O! H fA XA^N. A A / \ZNA A ^NX / X / X YYr i YTY YAr° °\ ° °\0F^A^1152 Y H J | Y)! H fo ^x\10^ 0 0\ 0FA^A1 HlA / YHM 6 1 H f 1153° ^A °\0< A oF^A208 DB1 / 163717029.3Docket No. 133186-5032-WO4. The antibody-drug conjugate of any one of claims 1-3, wherein L is a bond or a linker comprising one or more groups selected from C₁-C₆ alkyl, C=O, -NH-, ethylene glycol, optionally 2-50 or 2-10 ethylene glycol units, valine-citrulline (val-cit), 6-maleimidocaproyl (me), 6-succinimidylcaproyl, 6-(2.5-dioxo-3Z’-pyrrolidin-l-yl)caproyl. methoxy-polyethylene glycol maleimide 6 (MalPeg6), p-aminobenzylcarbamate (PABC), dimethylaminoethanol (DMAE), 3-maleimidopropanoyl (MP), 3-succinimidylpropanoyl, 3-(2.5-dioxo-3Z’-pyrrolidin-l- yl)propanoyl, hydrolyzed Peg-maleimides, hydrolyzed maleimide, hydrolyzed succinimide, p- aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2- pyridylthio) pentanoate (SPP), N- succinimidyl 4-(N-maleimidomethyl) cyclohexane- 1 carboxylate (SMCC), N-Succinimidyl (4- iodo-acetyl) aminobenzoate (SIAB), 6-maleimidocaproyl-valine-citrulline-p- aminobenzyloxycarbonyl (mc-val-cit-PAB), and 6-maleimidocaproyl-valine-citrulline-p- aminobenzylcarbamate (mc-val-cit-PABC), an amino acid, optionally (D)-valine, (L)-valine, (D)-alanine, and / or (L)-alanine, an amino acid sequence, optionally valine -alanine (Vai-Ala), alanine-phenylalanine (Ala-Phe), alanine-alanine-alanine (Ala-Ala-Ala), or glycine-glycine- phenylalanine-glycine (Gly-Gly-Phe-Gly), and maleimide.DB1 / 163717029.3 209Docket No. 133186-5032-WO5. The antibody-drug conjugate of any one of claims 1-4, wherein L is a bond or a linker comprising one or more groups selected from succinimide, an oxime, a bisulfone, a heterocycle, optionally a triazole or an isoxazolidine, an amide, and a thioether, an alkenyl phosphorous group, and an alkyl phosphorous group.

6. The antibody-drug conjugate of any one of claims 1-5, wherein L is a bond or a linker selected from:DB1 / 163717029.3 210Docket No. 133186-5032-WOwherein, XAAis an amino acid sequence having 1 to 5 amino acid moieties.

7. The antibody-drug conjugate of claim 6, wherein XAAis selected from alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (lie), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), valine (Val), selenocysteine, homo-alanine (a-aminobutyric acid), norvaline, norleucine, Val-Ala, Tyr-Arg, Phe-Arg, Val-Gln, Val-Cit, Asn-Asn, Tyr-Met, Leu-Gin, Val-Arg, Met-Thr, Phe-Gln, Thr-Thr, Val-Thr, Ala-Ala, Val-Met, Leu-Met, Ala-Asn, D-Val-D-Gln, D- Ala-D-Ala, Phe-Met, alanine-alanine-alanine, valine-alanine-alanine, glutamic acid-valine- citrulline, valine-lysine-glycine, glycine-glycine-phenylalanine-glycine, glutamic acid-aspartic acid-phenylalanine -tryptophan, glycine-phenylalanine-leucine-glycine, and alanine-leucine- alanine -leucine.DBl / 163717029.3 211Docket No. 133186-5032-WO8. The antibody-drug conjugate of any one of any one of claims 1-7, wherein L is a bond or a linker selected from:DBl / 163717029.3 212Docket No. 133186-5032-WO9. The antibody-drug conjugate of any one of claims 1-8, wherein L is10. The antibody-drug conjugate of any one of claims 1-8, wherein L isDB1 / 163717029.3 213Docket No. 133186-5032-WO11. The antibody-drug conjugate of any one of claims 1-10, wherein D is moiety 1021:

12. The antibody-drug conjugate of any one of claims 1-10, wherein D is moiety 1010:

13. The antibody-drug conjugate of any one of claims 1-10, wherein D is moiety 1062:

14. The antibody-drug conjugate of any one of claims 1-13, wherein n is an integer from 1 to 10.

15. The antibody-drug conjugate of any one of claims 1-14, wherein n is 4 or 8.

16. The antibody-drug conjugate of any one of claims 1-15, wherein the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 2,(b) a CDRH2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 3, andDBl / 163717029.3 214Docket No. 133186-5032-WO(c) a CDRH3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 4,and (ii) a light chain variable region (VL) that comprises:(a) a CDRL1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 6,(b) a CDRL2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 7, and(c) a CDRL3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO:8.

17. The antibody-drug conjugate of any one of claims 1-16, wherein the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 1, and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 5.

18. The antibody-drug conjugate of claim 17, wherein the antibody or antigen binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 1 and / or a VL comprising the amino acid sequence of SEQ ID NO: 5.

19. The antibody-drug conjugate of any one of claims 1-15, wherein the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 16,(b) a CDRH2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 17, and(c) a CDRH3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 18,and (ii) a light chain variable region (VL) that comprises:DBl / 163717029.3 215Docket No. 133186-5032-WO(a) a CDRL1 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 20,(b) a CDRL2 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 21, and(c) a CDRL3 comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 22.

20. The antibody-drug conjugate of any one of claims 1-15 or 19, wherein the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 15, and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to the amino acid sequence of SEQ ID NO: 19.

21. The antibody-drug conjugate of claim 20, wherein the antibody or antigen binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and / or a VL comprising the amino acid sequence of SEQ ID NO: 19.

22. The antibody-drug conjugate of any one of claims 1-15, wherein the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a VL that comprises an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.DBl / 163717029.3 216Docket No. 133186-5032-WO23. The antibody-drug conjugate of claim 22, wherein the antibody or antigen binding fragment thereof comprises a VH that comprises an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a VL that comprises an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

24. The antibody-drug conjugate of any one of claims 1-15, 22, or 23, wherein the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 23- 246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a light chain comprising an amino acid sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

25. The antibody-drug conjugate of claim 24, wherein the antibody or antigen binding fragment thereof comprises a heavy chain that comprises an amino acid sequence selected from SEQ ID NOs: 23-246; 471-518 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 247-249 and / or a light chain that comprises an amino acid sequence selected from SEQ ID NOs: 250-467; 519-555 or an amino acid sequence expressed from a nucleic acid sequence selected from SEQ ID NOs: 468-470.

26. The antibody-drug conjugate of any one of claims 1-25, wherein the antibody-drug conjugate has a drug-to-antibody ratio (DAR) ranging from about 1 to about 10, optionally wherein the DAR is about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10, optionally DAR is about 4, optionally DAR is about 8.

27. A pharmaceutical composition comprising the antibody-drug conjugate of any one of claims 1-26; and a pharmaceutically acceptable carrier.DBl / 163717029.3 217Docket No. 133186-5032-WO28. A method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the antibody-drug conjugate of any one of claims 1-26, or the pharmaceutical composition of claim 27.

29. The method of claim 28, wherein the cancer is selected from pancreatic cancer, breast cancer, prostate cancer, lymphoma, skin cancer, colon cancer, melanoma, malignant melanoma, ovarian cancer, brain cancer, primary brain carcinoma, head-neck cancer, glioma, glioblastoma, liver cancer, bladder cancer, non-small cell lung cancer, head or neck carcinoma, breast carcinoma, ovarian carcinoma, lung carcinoma, small-cell lung carcinoma, Wilms’ tumor, cervical carcinoma, testicular carcinoma, bladder carcinoma, pancreatic carcinoma, stomach carcinoma, colon carcinoma, prostatic carcinoma, genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma, myeloma, multiple myeloma, adrenal carcinoma, renal cell carcinoma, endometrial carcinoma, adrenal cortex carcinoma, malignant pancreatic insulinoma, malignant carcinoid carcinoma, choriocarcinoma, mycosis fungoides, malignant hypercalcemia, cervical hyperplasia, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, chronic granulocytic leukemia, acute granulocytic leukemia, hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi’s sarcoma, polycythemia vera, essential thrombocytosis, Hodgkin’s disease, non-Hodgkin’s lymphoma, soft-tissue sarcoma, osteogenic sarcoma, primary macroglobulinemia, or retinoblastoma, and the like.

30. The method of claim 28, wherein the cancer is acoustic neuroma, adenocarcinoma, angiosarcoma, astrocytoma, basal cell carcinoma, bile duct carcinoma, bladder carcinoma, brain cancer, breast cancer, triple -negative breast cancer (TNBC), bronchogenic carcinoma, cervical cancer, chordoma, choriocarcinoma, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, embryonal carcinoma, endotheliocarcinoma, ependymoma, epithelial carcinoma, esophageal cancer, Ewing’s tumor, fibrosarcoma, gastric cancer, glioblastoma multiforme, glioma, head and neck cancer, hemangioblastoma, hepatoma, kidney cancer, leiomyosarcoma, liposarcoma, lung cancer, lymphangioendotheliosarcoma, lymphangiosarcoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, myxosarcoma, nasal cancer, neuroblastoma, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinoma, papillary carcinoma, pinealoma, prostate cancer, rabdomyosarcoma, rectal cancer, renal cell carcinoma, retinoblastoma, sarcoma, DBl / 163717029.3 218Docket No. 133186-5032-WOsebaceous gland carcinoma, seminoma, skin cancer, squamous cell carcinoma, stomach cancer, sweat gland carcinoma, synovioma, testicular cancer, small cell lung carcinoma, throat cancer, uterine cancer, Wilms’ tumor, blood cancer, acute erythroleukemic leukemia, acute lymphoblastic B-cell leukemia, acute lymphoblastic T-cell leukemia, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, acute monoblastic leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocytic leukemia, acute promyelocytic leukemia, acute undifferentiated leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, hairy cell leukemia, myeloma, multiple myeloma, heavy chain disease, Hodgkin’s disease, non-Hodgkin’s lymphoma, polycythemia vera, Waldenstrom’s macroglobulinemia, pancreatic ductal adenocarcinoma (PDAC), prostate adenocarcinoma (PAC), colon adenocarcinoma (CAD), breast invasive carcinoma, lung squamous cell carcinoma (LSQCC), bladder urothelial carcinoma, gastrointestinal cancer.

31. The method of claim 28 or 30, wherein the cancer is triple-negative breast cancer (TNBC).

32. The method of claim 28 or 30, wherein the cancer is colorectal cancer.

33. The method of claim 28 or 30, wherein the cancer is pancreatic ductal adenocarcinoma (PDAC).

34. The method of claim 28 or 30, wherein the cancer is prostate adenocarcinoma (PAC).

35. The method of claim 28 or 30, wherein the cancer is colon adenocarcinoma (CAD).

36. The method of claim 28 or 29, wherein the cancer is non-small cell lung cancer (NSCLC).

37. The method of claim 28 or 30, wherein the cancer is breast invasive carcinoma.

38. The method of claim 28 or 30, wherein the cancer is lung squamous cell carcinoma (LSQCC).

39. The method of any one of claims 28 to 30, wherein the cancer is bladder carcinoma. DBl / 163717029.3 219Docket No. 133186-5032-WO40. The method of claim 28 or 30, wherein the cancer is bladder urothelial carcinoma.

41. The method of any one of claims 28-30, wherein the cancer is selected from gastrointestinal cancer, colorectal cancer, breast cancer, prostate cancer, and pancreatic cancer.

42. An antibody-drug conjugate having formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds CUB Domain-Containing Protein-1 (CDCP1);n is an integer from 1 to 20; andD is a moiety of formula 1021:wherein the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising the amino acid sequence as set forth in SEQ ID NO: 2, (b) a CDRH2 comprising the amino acid sequence as set forth in SEQ ID NO: 3, and(c) a CDRH3 comprising the amino acid sequence as set forth in SEQ ID NO: 4, and (ii) a light chain variable region (VL) that comprises:(a) a CDRL1 comprising the amino acid sequence as set forth in SEQ ID NO: 6, (b) a CDRL2 comprising the amino acid sequence as set forth in SEQ ID NO: 7, andDBl / 163717029.3 220Docket No. 133186-5032-WO(c) a CDRL3 comprising the amino acid sequence as set forth in SEQ ID NO: 8.

43. An antibody-drug conjugate having formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds CUB Domain-Containing Protein-1 (CDCP1);n is an integer from 1 to 20; andD is a moiety of formula 1010:wherein the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising the amino acid sequence as set forth in SEQ ID NO: 2, (b) a CDRH2 comprising the amino acid sequence as set forth in SEQ ID NO: 3, and(c) a CDRH3 comprising the amino acid sequence as set forth in SEQ ID NO: 4, and (ii) a light chain variable region (VL) that comprises:(a) a CDRL1 comprising the amino acid sequence as set forth in SEQ ID NO: 6, (b) a CDRL2 comprising the amino acid sequence as set forth in SEQ ID NO: 7, and(c) a CDRL3 comprising the amino acid sequence as set forth in SEQ ID NO: 8.DB1 / 163717029.3 221Docket No. 133186-5032-WO44. An antibody-drug conjugate having formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds CUB Domain-Containing Protein-1 (CDCP1);n is an integer from 1 to 20; andL isD is a moiety of formula 1062:wherein the antibody or antigen binding fragment thereof comprises:(i) a heavy chain variable region (VH) that comprises:(a) a CDRH1 comprising the amino acid sequence as set forth in SEQ ID NO: 2, (b) a CDRH2 comprising the amino acid sequence as set forth in SEQ ID NO: 3, and(c) a CDRH3 comprising the amino acid sequence as set forth in SEQ ID NO: 4, and (ii) a light chain variable region (VL) that comprises:(a) a CDRL1 comprising the amino acid sequence as set forth in SEQ ID NO: 6, (b) a CDRL2 comprising the amino acid sequence as set forth in SEQ ID NO: 7, and(c) a CDRL3 comprising the amino acid sequence as set forth in SEQ ID NO: 8.

45. An antibody-drug conjugate having formula (I):Ab-[L–D]nformula (I)wherein in formula (I):DB1 / 163717029.3 222Docket No. 133186-5032-WOAb is an antibody or antigen binding fragment thereof that binds CUB Domain-Containing Protein-1 (CDCP1);n is an integer from 1 to 20; and« j.Nz HO NH2D is a moiety of formula 1021:H? H / I\k NN l\kIwherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) that comprises the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (VL) that comprises the amino acid sequence of SEQ ID NO: 5.

46. An antibody-drug conjugate having formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds CUB Domain-Containing Protein-1 (CDCP1);n is an integer from 1 to 20; anda J. XToIy1 HL is o NH2D is a moiety of formula 1010:DB1 / 163717029.3 223Docket No. 133186-5032-WOwherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) that comprises the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (VL) that comprises the amino acid sequence of SEQ ID NO: 5.

47. An antibody-drug conjugate having formula (I):Ab-[L–D]nformula (I)wherein in formula (I):Ab is an antibody or antigen binding fragment thereof that binds CUB Domain-Containing Protein-1 (CDCP1);n is an integer from 1 to 20; andD is a moiety of formula 1062:wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) that comprises the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (VL) that comprises the amino acid sequence of SEQ ID NO: 5.

48. The antibody-drug conjugate of any one of claims 42-47, wherein n is 2, 4, or 8, optionally wherein n is 2, optionally wherein n is 4, optionally wherein n is 8.DB1 / 163717029.3 224Docket No. 133186-5032-WO49. The antibody-drug conjugate of any one of claims 42-47, wherein the antibody-drug conjugate has a drug-to-antibody ratio (DAR) of about 2, about 4, or about 8, optionally wherein DAR is about 2, optionally wherein DAR is about 4, optionally wherein DAR is about 8.

50. A method of treating a cancer comprising administering to a subject in need thereof a therapeutically effective amount of the antibody-drug conjugate of any one of claims 42-47.

51. The method of claim 50, wherein the cancer is triple-negative breast cancer (TNBC).

52. The method of claim 50, wherein the cancer is colorectal cancer.

53. The method of claim 50, wherein the cancer is pancreatic ductal adenocarcinoma (PDAC).

54. The method of claim 50, wherein the cancer is prostate adenocarcinoma (PAC).

55. The method of claim 50, wherein the cancer is colon adenocarcinoma (CAD).

56. The method of claim 49, wherein the cancer is non-small cell lung cancer (NSCLC).

57. The method of claim 50, wherein the cancer is breast invasive carcinoma.

58. The method of claim 50, wherein the cancer is lung squamous cell carcinoma (LSQCC).

59. The method of claim 50, wherein the cancer is bladder carcinoma.

60. The method of claim 50, wherein the cancer is bladder urothelial carcinoma.

61. The method of claim 50, wherein the cancer is selected from gastrointestinal cancer, colorectal cancer, breast cancer, prostate cancer, and pancreatic cancer.DB1 / 163717029.3 225

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