CA3065919A1 - Antibody construct conjugates - Google Patents

Antibody construct conjugates Download PDF

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CA3065919A1
CA3065919A1 CA3065919A CA3065919A CA3065919A1 CA 3065919 A1 CA3065919 A1 CA 3065919A1 CA 3065919 A CA3065919 A CA 3065919A CA 3065919 A CA3065919 A CA 3065919A CA 3065919 A1 CA3065919 A1 CA 3065919A1
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immune
amino acid
conjugate
seq
domain
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French (fr)
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Peter Armstrong Thompson
Badreddin EDRIS
Craig Alan Coburn
Peter Robert Baum
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ARS Pharmaceuticals Inc
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Silverback Therapeutics Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/71—Decreased effector function due to an Fc-modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/95—Fusion polypeptide containing a motif/fusion for degradation (ubiquitin fusions, PEST sequence)

Abstract

Various compositions are disclosed. The compositions of composition-immune stimulatory compound conjugates are also provided. Additionally provided are the methods of preparation and uses of the composition-immune stimulatory compound conjugates. This includes methods for treating disorders, such as cancer.

Description

DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME

NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME:
NOTE POUR LE TOME / VOLUME NOTE:

ANTIBODY CONSTRUCT CONJUGATES
PRIORITY
[0001] This application claims the benefit of priority under 35 U.S.C.
119(e) to U.S.
Provisional Application No. 62/516,667, filed June 7, 2017, the disclosure of which is incorporated herein by reference in its entirety.
BACKGROUND
[0002] One of the leading causes of death in the United States is cancer. The conventional methods of cancer treatment, like chemotherapy, surgery, or radiation therapy, tend to be either highly toxic or nonspecific to a cancer, or both, resulting in limited efficacy and harmful side effects. However, the immune system has the potential to be a powerful, specific tool in fighting cancers. In many cases tumors can specifically express genes whose products are required for inducing or maintaining the malignant state. These proteins may serve as antigen markers for the development and establishment of more specific anti-cancer immune response.
The immune response may include the recruitment of immune cells that target tumors expressing these antigen markers. Additionally, the immune cells may express genes whose products are important to proper immune function and may serve as markers for specific types of immune cells. The boosting of this specific immune response has the potential to be a powerful anti-cancer treatment that can be more effective than conventional methods of cancer treatment and can have fewer side effects.
INCORPORATION BY REFERENCE
[0003] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.
SUMMARY
[0004] Provided herein are immune-modulatory and immune-stimulatory conjugates. In certain embodiments, an immune-modulatory conjugate is provided comprising: (a) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to a first antigen; (b) a proteolysis targeting module, comprising: (i) a protein targeting moiety that binds to a target protein; (ii) an E3 ubiquitin ligase binding moiety; and (iii) a spacer S that is covalently bound to the protein targeting moiety and to the E3 ubiquitin ligase binding moiety, wherein the spacer is optionally has 1-25 consecutive non-hydrogen atoms; and (c) a linker L that is covalently attached to the antibody construct and to the proteolysis targeting module. The conjugate can be represented by one of the following formulae:
Ab = t 41401 (VII), _ 7 \ -(VIII), or _ / \ -Ab . . . =
(IX), wherein: Ab is the antibody construct; L is the linker; ULM is the E3 ubiquitin ligase binding moiety; IMC is the protein targeting moiety and comprises an immune-modulatory compound; S
is the spacer; n is selected from 1 to 20; and z is selected from 1 to 20. In some embodiments, the Fc domain of the conjugate is an Fc null.
[0005] In some embodiments, the E3 ubiquitin ligase is selected from the group consisting of Von Hippel-Lindaue E3 ubiquitin ligase (VHL), cereblon, mouse double minute 2 homolog (MDM2), AMFR, APC/Cdc20, APC/Cdhl, C6orf157, Cbl, CBLL1, CHFR, CHIP, DTL
(Cdt2), E6-AP, HACE1, HECTD1, HECTD2, HECTD3, HECW1, HECW2, HERC2, HERC3, HERC4, HERC5, HUWEl, HYD, ITCH, LNX1, mahogunin, MARCH-I, MARCH-II, MARCH-III, MARCH-IV, MARCH-VI, MARCH-VII, MARCH-VIII, MARCH-X, MEKK1, MIB1, MIB2, MycBP2, NEDD4, NEDD4L, Parkin, PELI1, Pirh2, PJA1, PJA2, RFFL, RFWD2, Rictor, RNF5, RNF8, RNF19, RNF190, RNF20, RNF34, RNF40, RNF125, RNF128, RNF138, RNF168, SCF/?-TrCP, SCF/FBW7, SCF/5kp2, SHPRH, SIAH1, SIAH2, SMURF1, SMURF2, TOPORS, TRAF6, TRAF7, TRIM63, UBE3B, UBE3C, UBR1, UBR2, UHRF2, WWP1, WWP2, and ZNRF1. In some further embodiments, the E3 ubiquitin ligase binding moiety binds to VHL, cereblon or MDM2.
[0006] In some embodiments, the protein targeting moiety binds to a protein selected from one of the groups consisting of: a) an aryl hydrocarbon receptor, androgen receptor, estrogen receptor, FK506-binding protein 12, fibroblast growth factor receptor substrate 2, phosphatidylinosito1-4,5-biphosphate 3-kinase, SMAD family member 3, bromodomain and extra-territorial family of proteins (BET), bromodomain-containing protein 4 member of the BET
family, Abelson tyrosine kinase, receptor-interacting serine/threonine-protein kinase 1, estrogen-related receptor, and transforming growth factor beta (TGF(3); or b) ALK, Bcr-Abl, BRAF, BTK, c-KIT, EGFR, ErbB2, JAK, MEK, MET, PDGFRB, RET, ROS1, Syk, SRC, TNIK, TNKS, TNKS2, TrkA, TrkB, TrkC, VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, FGFR3, FGFR4, CSF1R, RON/MST1R, TYR03, MERTK, AXL, PI3K, PI3K, MAP4K1, PERK, and KIT; or c) TGFPR2, TGFPR1, SMAD2, SMAD3, SMAD4, beta-catenin, CREBB2, Beta catenin/TCF4, beta catenin/LEF, beta catenin/CREBBP, YAP, TAZ, YAP/TAZ, TNKS1, TNKS2, MST1, MST2, NRAS, HRAS, KRAS, RASmut12, RASmut13, PERK (EIF2AK3), RON/MST1R, STAT3, MCT1, MCT2 and MCT4; or d) CSFR1, RON/MST1, PI3Kd, PI3Kg, PARP1, PD-L1, PP2A, A2ar, TYR03, AXL and MER.
[0007] In some embodiments, the first antigen is a tumor antigen. The tumor antigen can be MUC16, CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC, HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Ley, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, v 3, WT1, LMP2, HPV E6, HPV E7, EGFRvIII, Her-2/neu, MAGE A3, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyronsinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint fusion protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, MUC15, CA6, NAPI2B, TROP2, CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, LIV1, ROR1, or Fos-related antigen 1.
[0008] In some embodiments, the first antigen is an immune cell antigen, and can be an antigen present on the surface of an antigen presenting cell such as a dendritic cell or a macrophage. In some embodiments, the immune cell antigen is selected from the group consisting of CD40, DEC-205, PD-L1, PD-1, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, and CD32B.
[0009] In some embodiments, the protein targeting moiety can be a peptide or a non-proteinaceous molecule. In some embodiments, the proteolysis targeting module is selected from compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6 and 2-1, as disclosed herein. In some embodiments, the linker L is a cleavable linker. In some embodiments, the linker L is a non-cleavable linker. In some embodiments, the linker L is covalently bound to the antibody construct at a cysteine residue, an engineered cysteine residue, a lysine residue, a glutamate residue, or a glutamine residue of the antibody construct or is covalently bound to the antibody construct using a Sortase linker.
[0010] In some embodiments, the spacer S is an optionally substituted C1-25 alkylene or optionally substituted C1-25 heteroalkylene, wherein the heteroalkylene is a C1-24 alkylene chain interspersed with one or more groups independently selected from: -0-, -S-, -NH2-, and -C(0)NH-; and optionally substituted with a reactive group, Rx, that can form a functional group selected from an amide bond, an ester bond, an ether bond, a carbonate bond, a carbamate bond, or a thioether bond. The spacer can be optionally substituted with C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, -(CH20).1H, -(CH2CH20)n1fl, -(CH20)n1CH3, -C(0)0H or -NH2, wherein n1 is from 1 to 8. In some embodiments the spacer is substituted with Rx. In some embodiments, the linker is unsubstituted.
[0011] In some embodiments, the antibody construct further comprises a second binding domain.
The second binding domain can specifically bind to an antigen on an immune cell. The immune cell antigen is selected from the group consisting of CD40, PD-1, PD-L1, DEC-205, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, and CD32B. In some embodiments, the second binding domain is attached to the antibody construct at a C-terminal end of the Fc domain.
[0012] In some embodiments, the Fc domain is an Fc domain variant comprising at least one amino acid residue change as compared to a wild type sequence of the Fc domain. In some embodiments, the Fc domain is an Fc domain variant that decreases binding of the Fc domain to an Fc receptor. In some embodiments, the at least one amino acid residue change in the Fc domain is: a) F243L, R292P, Y300L, L235V, and P396L, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898; b) 5239D and 1332E, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO:
898; or c) 5298A, E333A, and K334A, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898. In some embodiments, the at least one amino acid residue change in the Fc domain is: a) N297A, N297G, N297Q, N297D as in Eu index of Kabat numbering and relative to SEQ ID NO: 898; or b) K322A/L234A/L235A N296A as in the EU index of Kabat numbering and relative to SEQ ID NO: 898; or c) L234F/L235E/P3315 N296A as in the EU
index of Kabat numbering and relative to SEQ ID NO: 898; or d) P329G/L234A/L235A as in the EU
index of Kabat numbering and relative to SEQ ID NO: 898.
[0013] Also provided is a pharmaceutical composition comprising a conjugate as described herein along with a pharmaceutically acceptable excipient. In the pharmaceutical composition, the average ratio of proteolysis targeting modules to antibody construct in the conjugate can be from 2 to 6, from 3 to 5 or 1 to 3. The pharmaceutical composition can be lyophilized.
[0014] Also provided are methods of treating cancer comprising administering a conjugate as described herein, or a pharmaceutical composition of a conjugate as described herein, to a subject in need thereof. In some embodiments, the cancer is a solid tumor, such as breast cancer, pancreatic cancer, colorectal cancer, renal cell cancer, gastric cancer, or lung cancer. In some embodiments, the pharmaceutical composition is administered parenterally. In some embodiments, the pharmaceutical composition is administered intravenously.
[0015] In certain aspects, the disclosure also provides immune-stimulatory conjugates comprising: (a) an immune-stimulatory compound that binds to a target protein to stimulate an immune response by stimulating the activity of the target protein, reducing immune inhibition by the target protein or increasing degradation of the target protein; (b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to at least a first antigen and wherein the Fc domain binds to an Fc receptor; and (c) a linker, wherein the linker is covalently bound to the antibody construct and the linker is covalently bound to the immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound of the conjugate (i.e, attached to the conjugate) to the target protein is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the target protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound of the conjugate is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound of the conjugate (i.e, attached to the conjugate) to the target protein is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the target protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound of the conjugate is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the Fc domain is an Fc null.
[0016] In certain embodiments, the disclosure provides an immune-stimulatory conjugate comprising: (a) an immune-stimulatory compound that binds to a protein active site to stimulate an immune response; (b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to at least a first antigen and wherein the Fc domain binds to an Fc receptor; and (c) a linker, wherein the linker is covalently bound to the antibody construct and the linker is covalently bound to the immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of immune-stimulatory compound of the conjugate to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound of the conjugate (attached to the conjugate )is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of immune-stimulatory compound of the conjugate to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound of the conjugate (attached to the conjugate) is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound.
[0017] In certain embodiments, the disclosure provides an immune-stimulatory conjugate comprising: (a) an immune-stimulatory compound that binds to a protein active site of a binding protein to stimulate an immune response by inhibition of the activity of the binding protein; (b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to at least a first antigen and wherein the Fc domain binds to an Fc receptor; and (c) a linker, wherein the linker is covalently bound to the antibody construct and the linker is covalently bound to the immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound of the conjugate (attached to the conjugate) to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the IC50 of the immune-stimulatory compound of the conjugate (attached to the conjugate) is no greater than 300-fold the IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound of the conjugate (attached to the conjugate) to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the IC50 of the immune-stimulatory compound of the conjugate (attached to the conjugate) is no greater than 300-fold the IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the Fc domain is an Fc null.
[0018] In certain embodiments, the disclosure provides an immune-stimulatory conjugate comprising: (a) an immune-stimulatory compound that binds to a protein active site of a binding protein to stimulate an immune response by increasing degradation of the binding protein; (b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to at least a first antigen and wherein the Fc domain binds to an Fc receptor; and (c) a linker, wherein the linker is covalently bound to the antibody construct and the linker is covalently bound to the immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound of the conjugate (attached to the conjugate) to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the IC50 of the immune-stimulatory compound of the conjugate is no greater than 300-fold the IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound of the conjugate (attached to the conjugate) to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the IC50 of the immune-stimulatory compound of the conjugate is no greater than 300-fold the IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the Fc domain is an Fc null.
[0019] In certain embodiments, the EC50 or IC50 of the immune-stimulatory compound of the conjugate is no greater than 100-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. The EC50 or IC50 of the immune-stimulatory compound of the conjugate may be no greater than 10-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. The EC50 or IC50 of the immune-stimulatory compound of the conjugate may be equivalent to or less than the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound.
[0020] In certain embodiments, the EC50 or IC50 of the immune stimulatory compound on an antigen bearing cell is equivalent to or less than the EC50 or IC50 of a control compound on the antigen bearing cell and the EC50 or IC50 of the immune-stimulatory conjugate is 5-fold greater or more than the EC50 or IC50 of the control compound for a non-antigen bearing cell.
[0021] The immune-stimulatory compound of the conjugate may have a Kd for binding to the protein active site of no greater than 50 times the Kd for binding of a control compound to the protein active site, wherein the control compound is the unbound immune-stimulatory compound. The immune-stimulatory compound of the conjugate may have a Kd for binding to the protein active site of no greater than 10 times the Kd for binding of a control compound to the protein active site, wherein the control compound is the unbound immune-stimulatory compound. The immune-stimulatory compound of the conjugate may have a Kd for binding to the protein active site of equivalent to or less than the Kd for binding of a control compound to the protein active site, wherein the control compound is the unbound immune-stimulatory compound.
[0022] In certain aspects, the disclosure provides an immune-stimulatory conjugate comprising:
(a) an immune-stimulatory compound that binds to a protein active site to stimulate an immune
23 response; (b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to a first antigen and wherein the Fc domain binds to an Fc receptor; and (c) a linker comprising 5-100 consecutive atoms attachment sites, wherein one attachment site of the linker is covalently bound to the antibody construct and another attachment site of the linker is covalently bound to the immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound when bound to a the linker to the protein active site is no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound of the conjugate is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct; and wherein the Kd for binding of the immune-stimulatory compound when bound to a the linker to the protein active site is no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound of the conjugate is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In some embodiments, the Fc domain is an Fc null.
[0023] In certain embodiments, the EC50 or IC50 of the immune-stimulatory compound when bound to the 5-100 atom linker is no greater than 100-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. In certain embodiments, the EC50 or IC50 of the immune-stimulatory compound when bound to the 5-100 atom linker is no greater than 10-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound. The EC50 or IC50 of the immune-stimulatory compound when bound to the 5-100 atom linker may be equivalent to or less than the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound.
[0024] In certain embodiments, the Kd for binding of the immune-stimulatory compound when bound to the 5-100 atom linker to the protein active site may be no greater than 50 times the Kd for binding of a control compound to the protein active site, wherein the control compound is the unbound immune-stimulatory compound. The Kd for binding of the of the immune-stimulatory compound when bound to a 5-100 atom linker to the protein active site may be no greater than 10 times the Kd for binding of a control compound to the protein active site, wherein the control compound is the unbound immune-stimulatory compound. The Kd for binding of the immune-stimulatory compound when bound to a 5-100 atom linker to the protein active site may be equivalent to or less than the Kd for binding of a control compound to the protein active site wherein the control compound is the unbound immune-stimulatory compound.
[0025] In certain embodiments, the immune-stimulatory conjugate described herein comprises moiety that binds to the binding protein and an E3 ubiquitin ligase binding moiety. The E3 ubiquitin ligase binding moiety may bind to, for example, VHL, cereblon or MDM2. The E3 ubiquitin ligase binding moiety may be selected from among E3 targeting compounds. The E3 ubiquitin ligase binding moiety may be attached to the linker or may be part of the linker. In certain embodiments, the E3 ubiquitin ligase binding moiety attached to the linker, wherein the E3 ubiquitin ligase binding moiety is bound through a first linker having 5-100 consecutive atoms between attachment sites to the immune-stimulatory compound and the E3 ubiquitin ligase binding moiety is bound through a second linker having 5-100 consecutive atoms between attachment points to the antibody construct.
[0026] In certain embodiments, the immune-stimulatory compound is a kinase inhibitor and the protein active site is a kinase active site. In certain embodiments, the linker is covalently bound to the kinase inhibitor at a position on the kinase inhibitor that is at or near the solvent interface of the kinase active site as determined by modeling of the kinase inhibitor in the kinase active site. In certain embodiments, the linker is covalently bound to the kinase inhibitor at a position on the kinase inhibitor such that when the kinase inhibitor is bound to the active site, the linker extends out from the kinase active site into the solvent, as determined by modeling of the kinase inhibitor in the kinase active site. In certain embodiments, the kinase inhibitor may be selected from an inhibitor of ALK, Bcr-Abl, BRAF, BTK, c-KIT, EGFR, ErbB2, JAK, MEK, MET, PDGFRB, RET, ROS1, Syk, SRC, TGFPR2, TNIK, TNKS, TNKS2, TrkA, TrkB, TrkC, VEGF, VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, FGFR3, FGFR4, CSF1R, RON/MST1R, TYR03, MERTK, AXL, PI3Kdelta PI3Kgamma, MAP4K1, PERK, and combinations thereof.
[0027] In certain embodiments, the immune-stimulatory compound is selected from a toll-like receptor agonist, STING agonist, or RIG-I agonist. The immune-stimulatory compound may be a toll-like receptor (TLR) agonist selected from a TLR1 agonist, a TLR2 agonist, a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR6 agonist, a TLR7 agonist, a TLR8 agonist, a TLR9 agonist, or a TLR10 agonist. The immune-stimulatory compound may be selected from a pyrimidine, a purine, a guanine nucleoside, an 8-oxoadenine, an imidazoquinoline, a thiazoquinoline, a 2-aminoimidazole, a furo[2,3-c]pyridine, a furo[2,3-c]quinoline, a 2-aminobenzimidazole, a 2-aminoquinoline, and a 2-aminobenzazepine. The immune-stimulatory compound may bind to a G protein-coupled receptor (GCPR), an ion channel, a membrane transporter, a phosphatase or an endoplasmic reticulum (ER) protein.
[0028] In certain embodiments, the immune-stimulatory compound is an antagonist of the GPCR
A2aR, the sphingosine 1-phosphate receptor 1, prostaglandin receptor EP3, prostanglandin receptor E2, Frizzled, CXCR4 or an LPA receptor. The immune-stimulatory compound may be an ion channel agonist for CRAC, Kv1.3 or KCa3.1. The immune-stimulatory compound may be an inhibitor of HSP90 or AAA-ATPase p97.
[0029] In certain embodiments, the immune-stimulatory conjugate has immune-stimulatory activity while attached to the conjugate or the linker and without undergoing cell processing such as by endosomal or lysosomal degradation, e.g., to release the immune-stimulatory compound or a modified form of the compound from the conjugate or linker. In certain embodiments, the linker is a non-cleavable linker. The linker may be selected from the group consisting of Fleximer linkers. The linker may comprise one or more carbamate or amide linkages when attached to an immune-stimulatory compound. The linker may be selected from a linker is Rx Rx represented by one of the following formula: -- Ra -- , -- Ra -- , 0 -- 0 0 0 Njõ N
NJ= ,ON)=.(4Rx 0 Rx , F

F N peptide ¨Rx F , or H
, wherein Rx is a reactive moiety and wherein Ra is selected from the group consisting of hydrogen, alkyl (e.g., Ci-C8 alkyl), sulfonate and methyl sulfonate. The linker may be attached to the antibody construct at a cysteine or lysine residue of the antibody construct.
[0030] In certain embodiments, the first antigen is a tumor antigen. The first antigen may be at least 80% or 100% homologous to CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6 E7, Her-2/neu, p53 nonmutant, NY-ES0-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2õ TRAILl, MAGE A4, MAGE
C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B
(UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, PD-L1, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof.
[0031] In certain embodiments, the antibody construct further comprises a second target binding domain. In certain embodiments, the target binding domain specifically binds an antigen on an immune cell. The target binding domain may be attached (e.g., conjugated or linked) to the antibody construct at a C-terminal end of the Fc domain. The antigen binding domain may be from an antibody or non-antibody scaffold. The antigen binding domain may be at least 97%
homologous to an antigen binding domain from an antibody or non-antibody scaffold. The antibody construct may be a human antibody or a humanized antibody. The Fc domain may be an Fc domain variant comprising at least one amino acid residue change as compared to a wild type sequence of the Fc domain. The Fc domain may be at least about 80% homologous to an Fc domain from an antibody, wherein the Fc domain from an antibody comprises amino acid residues 216 to 447 of an IgG1 (within SEQ ID NO: 898), amino acid residues 216 to 443 of an IgG2 (within SEQ ID NO: 899), or amino acid residues 216 to 444 of an IgG4 (within SEQ ID
NO: 900).
[0032] In certain embodiments, the Fc domain may have at least one amino acid residue change as compared to a wildtype Fc domain. In certain embodiments, the Fc domain may have at least one amino acid residue change as compared to a wildtype Fc domain, wherein the Fc domain is at least 80% homologous to SEQ ID NO: 898. The at least one amino acid residue change may be in an IgG Fc domain: a) F243L, R292P, Y300L, L235V, and P396L, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO:898; b) 5239D
and 1332E, wherein numbering of amino acid residues in the Fc domain is relative to SEQ
ID NO: 898; or c) 5298A, E333A, and K334A, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 296. The Fc domain may have at least one amino acid residue change as compared to wildtype, wherein the Fc domain is at comprises at least 80%
homologous to SEQ
ID NO: 898, and wherein the at least one amino acid residue change is: (a) N296A wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO:
898; or (b) N296G
N296A wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO:
898; or (c) K322A/L234A/L235A N296A wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898; or (d) L234F/L235E/P331S N296A wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898.
[0033] In certain embodiments, the Kd for binding of the antigen binding domain to the first antigen in the presence of the immune-stimulatory compound is less than about 100 nM and is equal to, or up to no greater than about 10 times the Kd of the binding of the antigen binding domain to the first antigen in the absence of the immune-stimulatory compound;
and the Kd for binding of the Fc domain to the Fc receptor in the presence of the immune-stimulatory compound is equal to, or up to no greater than about 10 times the Kd for the binding of the Fc domain to the Fc receptor in the absence of the immune-stimulatory compound.
[0034] In certain embodiments, the molar ratio of immune-stimulatory compound to antibody in a conjugate is less than 5. In certain embodiments, the average molar ratio of immune-stimulatory compound to antibody construct in a composition of conjugates is less than 5. In certain embodiments, the average molar ratio of immune-stimulatory compound to antibody construct in a composition of conjugates from 1 to 3, 3 to 5, or about 2.
[0035] The linker may be bound to the antibody construct at an amino acid residue that does not interfere with the Fc domain binding to the Fc receptor. The linker may not be attached to an amino acid residue of an IgG Fc domain selected from a group consisting of:
221, 224, 227, 228, 230, 231, 223, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 249, 250, 258, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 275, 276, 278, 280, 281, 283, 285, 286, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 302, 305, 313, 318, 323, 324, 325, 327, 328, 329, 330, 331, 332, 333, 335, 336, 396, or 428, wherein numbering of amino acid residues in the Fc domain is according to the EU index as in Kabat.
[0036] The linker is bound to the antibody construct at an amino acid of an IgG Fc domain selected from a group consisting of: 221, 224, 227, 228, 230, 231, 223, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 247, 249, 250, 258, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 275, 276, 278, 280, 281, 283, 285, 286, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 302, 305, 313, 318, 323, 324, 325, 327, 328, 329, 330, 331, 332, 333, 335, 336, 396, or 428, wherein numbering of amino acid residues in the Fc domain is according to the EU
index as in Kabat.
[0037] In certain embodiments, the Fc domain is an IgG Fc domain selected from a group consisting of a human IgG1 Fc domain, a human IgG2 Fc domain, a human IgG3 Fc domain, and a human IgG4 Fc domain. In certain aspects, the immune-stimulatory conjugate induces the secretion of cytokines by an antigen presenting cell.
[0038] In certain aspects, the disclosure provides a pharmaceutical composition comprising immune-stimulatory conjugates as described herein and a pharmaceutically acceptable excipient.
In certain aspects, the disclosure provides a method of treating cancer, comprising administering to a subject in need thereof an immune-stimulatory conjugate described herein.
In certain aspects, the disclosure provides a method of treating cancer, comprising administering to a subject in need thereof a pharmaceutical composition comprising immune-stimulatory conjugates as described herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0039] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative aspects, in which the principles of the disclosure are utilized, and the accompanying drawings of which:
[0040] FIGURE 1 illustrates a schematic of a conjugate comprising an antibody and a second binding domain. The antibody contains two heavy chains as shown in gray and two light chains as shown in light gray. A portion of the heavy chains contain Fc domains (705 and 720). The antibody comprises a binding domain comprising two antigen binding sites (710 and 715). The second binding domain is attached to the antibody (780 and 785), for example, at the C-terminus of the heavy chains.
[0041] FIGURE 2 illustrates a schematic of an exemplary conjugate. The conjugate comprises an antibody, which contains two heavy chains as shown in gray and two light chains as shown in light gray. The antibody comprises a binding domain comprising two antigen binding sites (910 and 915), and a portion of the heavy chains contain Fc domains (905 and 920).
The immune-stimulatory compounds (930 and 940) are attached to the antibody by linkers (960 and 970). A
second binding domain is attached to the antibody (980 and 985), for example, at the C-terminus of the heavy chains.
[0042] FIGURE 3 illustrates a schematic of an exemplary conjugate. The conjugate comprises the Fc region of an antibody with the heavy chains shown in gray, and two scaffolds as shown in light gray. The conjugate comprises a first binding domain comprising two antigen binding sites (1110 and 1115) in the scaffolds, and a portion of the heavy chains contain Fc domains (1105 and 1120). The immune-stimulatory compounds (1130 and 1140) are conjugated to the Fc domains by linkers (1160 and 1170). A second binding domain is attached to the conjugate (1180 and 1185), for example, at the C-terminus of the heavy chains.
[0043] FIGURE 4 illustrates a schematic of an exemplary conjugate. The conjugate comprises the F(ab')2 region of an antibody with the Fab portions of heavy chains shown in gray and light chains shown in light gray, and two scaffolds as shown in dark gray. The conjugate comprises a first binding domain comprising two antigen binding sites (1310 and 1315), and a portion of two scaffolds contain Fc domains (1340 and 1345). The immune-stimulatory compounds (1330 and 1340) are attached to the conjugate by linkers (1360 and 1370). A second binding domain is attached to the Fc domains (1380 and 1385).
[0044] FIGURE 5 illustrates a schematic of an exemplary conjugate. The conjugate contains two scaffolds as shown in light gray and two scaffolds as shown in dark gray.
The conjugate comprises a first binding domain comprising two antigen binding sites (1510 and 1515), and a portion of the two dark gray scaffolds contain Fc domains (1540 and 1545). The immune-stimulatory compounds (1530 and 1540) are conjugated to the conjugate by linkers (1560 and 1570). A second binding domain is attached to the conjugate (1580 and 1585).
[0045] FIGURE 6 illustrates a schematic of a conjugate comprising an antibody and a second binding domain. The antibody contains two heavy chains as shown in gray and two light chains as shown in light gray. A portion of the heavy chains contain Fc domains (1705 and 1720). The antibody comprises a binding domain comprising two antigen binding sites (1710 and 1715). The second binding domain is attached to the antibody (1780 and 1785), for example, at the C-terminus of the light chains.
[0046] FIGURE 7 illustrates a schematic of an exemplary conjugate. The conjugate comprises an antibody, which contains two heavy chains as shown in gray and two light chains as shown in light gray. The antibody comprises a binding domain comprising two antigen binding sites (1910 and 1915), and a portion of the heavy chains contain Fc domains (1905 and 1920). The immune-stimulatory compounds (1930 and 1940) are conjugated to the antibody by linkers (1960 and 1970). A second binding domain is attached to the antibody (1980 and 1985), for example, at the C-terminus of the light chains.
[0047] FIGURE 8 illustrates a schematic of an exemplary conjugate. The conjugate comprises an Fc region of an antibody shown in gray, and two scaffolds as shown in light gray. The conjugate comprises a first binding domain comprising two antigen binding sites (2110 and 2115) in the scaffolds, and a portion containing Fc domains (2105 and 2120).
The immune-stimulatory compounds (2130 and 2140) are conjugated to the antibody construct by linkers (2160 and 2170). A second binding domain is attached to the antibody (2180 and 2185).
[0048] FIGURE 9 illustrates a schematic of an exemplary conjugate. The conjugate comprises the F(ab')2 region of an antibody with heavy chains shown in gray and light chains shown in light gray, and two scaffolds as shown in dark gray. The conjugate comprises a first binding domain comprising two antigen binding sites (2310 and 2315), and a portion of two scaffolds contain Fc domains (2340 and 2345). The immune-stimulatory compounds (2330 and 2340) are conjugated to the antibody by linkers (2360 and 2370). A second binding domain is attached to the antibody (2380 and 2385), for example, at the C-terminus of the light chains.
[0049] FIGURE 10 illustrates a schematic of an exemplary conjugate. The conjugate contains two scaffolds as shown in light gray and two scaffolds as shown in dark gray.
The conjugate comprises a first binding domain comprising two antigen binding sites (2510 and 2515), and a portion of the two dark gray scaffolds contain Fc domains (2540 and 2545). The immune-stimulatory compounds (2530 and 2540) are conjugated to the antibody construct by linkers (2560 and 2570). A second binding domain is attached to the conjugate (2580 and 2585).
[0050] FIGURE 11 illustrates a schematic of an antibody construct comprising an antibody. The antibody contains two heavy chains and two light chains. A portion of the heavy chains contain Fc domains (2705 and 2720). The antibody comprises a binding domain comprising two antigen binding sites shown in black (2710 and 2715).
[0051] FIGURE 12 illustrates a schematic of an antibody construct comprising an antibody. The antibody contains two heavy chains and two light chains. A portion of the heavy chains contain Fc domains (2925 and 2930). The antibody comprises a first binding domain comprising two antigen binding sites shown in black (2910 and 2915). The antibody comprises a second binding domain comprising two single chain variable fragments (2905 and 2920) attached to a C-terminus of the light chains. A single chain variable fragment can be attached to a light chain chain at a heavy chain variable domain of the single chain variable fragment.
A single chain variable fragment can be attached to a light chain at a light chain variable domain of the single chain variable fragment.
[0052] FIGURE 13 illustrates a schematic of an antibody construct comprising an antibody. The antibody contains two heavy chains and two light chains. A portion of the heavy chains contain Fc domains (3120 and 3125). The antibody comprises a first binding domain comprising two antigen binding sites shown in black (3110 and 3115). The antibody comprises a second binding domain comprising two single chain variable fragments (3130 and 3135) attached to a C-terminus of the heavy chains. A single chain variable fragment can be attached to a heavy chain chain at a heavy chain variable domain of the single chain variable fragment.
A single chain variable fragment can be attached to a heavy chain at a light chain variable domain of the single chain variable fragment.
[0053] FIGURE 14 illustrates a schematic of an antibody construct comprising an antibody. The antibody contains two heavy chains and two light chains. A portion of the heavy chains contain Fc domains (3330 and 3335). The antibody comprises a first binding domain comprising two antigen binding sites shown in black (3310 and 3315). The antibody comprises a second binding domain comprising two single chain variable fragments (3320 and 3325) attached to a C-terminus of the light chains. A single chain variable fragment can be attached to a light chain chain at a heavy chain variable domain of the single chain variable fragment.
A single chain variable fragment can be attached to a light chain at a light chain variable domain of the single chain variable fragment. The antibody comprises a third binding domain comprising two single chain variable fragments (3340 and 3345) attached to a C-terminus of the heavy chains. A single chain variable fragment can be attached to a heavy chain chain at a heavy chain variable domain of the single chain variable fragment. A single chain variable fragment can be attached to a heavy chain at a light chain variable domain of the single chain variable fragment.
[0054] FIGURE 15A sets forth a structure of an immune-stimulatory compound (left) and an immune-stimulatory compound with an amine handle (right top).
[0055] FIGURE 15B shows the x-ray crystal structure and binding orientation (pdb code 5D7A) of the immune-stimulatory compound as described in FIGURE 15A in a TNIK (TRAF2 and NCK-interacting protein kinase) active site. Specific interactions between the inhibitor and the TNIK active site are described in Masuda et al., TNIK inhibition abrogates colorectal cancer sternness, (2016) Nat Commun 7: 12586-12586.
[0056] FIGURE 15C shows a close up of the binding orientation of the immune-stimulatory compound as described in FIGURE 15A in a TNIK active site, where the linker and antibody portions are pointing away and sitting outside of the active site.
[0057] FIGURE 16 sets forth a structure of an immune-stimulatory compound (left) and an immune-stimulatory compound with an amine handle and linker surrogate (right).
The structure on the right illustrates that the immune-stimulatory compound is predicted to sit in the enzyme active site, whereas the amine handle and linker surrogate are predicted to sit outside of the enzyme active site, in the solvent.
[0058] FIGURE 17A sets forth a structure of an immune-stimulatory compound (left) and an immune-stimulatory compound with a linker surrogate (left side of molecule on right).
[0059] FIGURE 17B shows the x-ray crystal structure and binding orientation (pdb code 5E91) of the immune-stimulatory compound as described in FIGURE 17A in a TGFPR2 (transforming growth factor, beta receptor II) active site. Specific interactions between the inhibitor and the TGFPRII active site are described in Tebben et al., Crystal structures of apo and inhibitor-bound TGFbetaR2 kinase domain: insights into TGFbetaR isoform selectivity, (2016) Acta Crystallogr., Sect.D 72: 658-674.
[0060] FIGURE 17C shows a close up of the binding orientation of the immune-stimulatory compound as described in FIGURE 17A in a TGFPR2 active site, where the linker and antibody construct portions are pointing away and sitting outside of the active site.
[0061] FIGURE 18A sets forth a structure of an immune-stimulatory compound (left) and an immune-stimulatory compound with an amine handle (upper left in molecule on right).
[0062] FIGURE 18B shows the x-ray crystal structure and binding orientation (pdb code 3KR8) of the immune-stimulatory compound as described in FIGURE 18A in a TNKS
(tankyrase) active site.
[0063] FIGURE 18C shows a close up of the binding orientation of the immune-stimulatory compound as described in FIGURE 18A in a TNKS active site, where the linker and antibody construct portions are pointing away and sitting outside of the active site.
Specific interactions between the inhibitor and the human tankyrase 2 - catalytic PARP domain active site are described in Karlberg et al., Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor, (2010) J.Med.Chem. 53: 5352-5355.
[0064] FIGURE 19A shows a structure of an immune-stimulatory compound (left) and an immune-stimulatory compound with two amine handles (on right side of molecule on the right).
[0065] FIGURE 19B shows the x-ray crystal structure and binding orientation (pdb code 4191) of the immune-stimulatory compound as described in FIGURE 19A with dual site binding in the TNKS (tankyrase) active site. Specific interactions between the inhibitor and human tankyrase 1 are described in Bregman et al, Discovery of a class of novel tankyrase inhibitors that bind to both the nicotinamide pocket and the induced pocket, (2013) J.Med.Chem. 56:
1341-1345.
[0066] FIGURE 19C shows a close up of the binding orientation of the immune-stimulatory compound as described in FIGURE 19A in a TNKS active site, where the linker and antibody portions are pointing away and sitting outside of the active site.
[0067] FIGURE 20A illustrates a schematic of an exemplary conjugate and its molecular target.
The conjugate comprises an antibody (3405) attached to a linker (3410) that is attached to a drug (3415) at the opposite end of the antibody (3405). The molecular target (3420) has an active site (3425) that is complementary to the drug (3415).
[0068] FIGURE 20B illustrates a schematic of an active exemplary conjugate that is bound to the the molecular target's active site. The drug (3415) sits within the active site of the molecular target (3420). The linker (3410) and antibody (3405) sit outside of the active site (3430).
[0069] FIGURE 20C illustrates a schematic of an active drug (3415) and linker (3410) that is bound to the molecular target (3420).
[0070] FIGURE 20D illustrates a schematic of an active drug (3415) that is bound to the molecular target (3420).
[0071] FIGURE 21A, FIGURE 21B, and FIGURE 21C show the results of an assay for degradation of TFGf3R2 by a TGFPR2-VHL PROTAC anti-HER2 antibody conjugate.
[0072] FIGURE 22A and FIGURE 22B show the results of an assay for antigen targeted degradation of TGFPR2 by an antibody conjugate with a PROTAC having VHL or Cereblon E3 binding moieties.
[0073] FIGURE 23A and FIGURE 23B show the results of an assay for cellular levels of TGFPR2 and TGFPR1 in the presence of a TGFPR2/TGFPR1-VHL PROTAC with or without the addition of a proteasome inhibitor.
DETAILED DESCRIPTION
[0074] Additional aspects and advantages of the present disclosure will become apparent to those skilled in this art from the following detailed description, wherein illustrative aspects of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different aspects, and its several details are capable of modifications in various respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.
[0075] As used herein, "potency" generally refers to measured bioactivity and may be quantified as an EC50 or IC50. Potency refers to the amount of a compound or conjugate needed to give an effect. For example, the potency of an immune-stimulatory compound which requires a lower amount of the immune-stimulatory compound compared with a different immune-stimulatory compound can be considered to have greater potency. Furthermore, the different immune-stimulatory compound requires a greater amount of the different immune-stimulatory compound to generate a response, and can therefore be considered lower potency.
Potencies of bioactive compounds or conjugates may be measured over a concentration range and can be reported as those molar concentrations required to elicit or inhibit a percentage of the measured bioresponse.
For example, a concentration required to stimulate 50% of observed maximal activity in the assay may be reported as an effective concentration 50 (EC50), to stimulate 90% activity as an EC90, or to stimulate 10% activity as an EC10. For example, a concentration of an antagonist required to give 50% maximal inhibition of a biological activity may be reported as an inhibitory concentration 50 (IC50), to inhibit 90% as an IC90, or to inhibit 10% as an IC10. This may allow for a comparison of the potencies of bioactive compounds on a molar basis by comparison of their EC or IC values for a given bioassay. For example, an immune-stimulatory conjugate or an immune-stimulatory compound with an EC50 or IC50 that is greater than 300 times the EC50 or IC50 of a control requires 300-fold higher, or more than 300-fold higher, concentration compared to the control to achieve a 50% bioresponse and has a potency weaker than the control by at least 300-fold. Therefore, an immune-stimulatory compound or conjugate that has an EC50 or IC50 not greater than about 300 times the EC50 or IC50 of a control compound may require no more than a 300-fold higher concentration than the control compound to achieve a 50% maximal bioresponse, no greater than 100 times the EC50 or IC50 requires no more than 100-fold higher concentration and no greater than 10 times the EC50 or IC50 requires no more than 10 times the concentration of the control. The potency of the immune-stimulatory compound or conjugate may be within 300-fold or better, 100-fold or better, or 10-fold or better the potency of the control.
[0076] As used herein, "control compound" refers to, in a case of an immune-stimulatory compound, the compound before attachment to a linker and antibody construct;
in the case of an antibody construct, the construct before attachment of the linker and immune-stimulatory compound; or, in the case of a conjugate including an E3 ubiquitin ligase binding moiety, control compound refers to the immune-stimulatory compound attached to a linker that is attached to an E3 ubiquitin ligase binding moiety.
[0077] An "immune-stimulatory compound" as described herein, also referred to herein as an immune-stimulatory agent or molecule, refers to a molecule that stimulates the immune system by inducing activation or increasing activity of any of its components. For example, an immune stimulatory compound may bind directly to a component of the immune system and activate or increase an activity of the immune system or a component thereof. An immune stimulatory compound may also bind to an inhibitory component of the immune system and inactivate or decrease the activity of that component, thereby increasing an activity of the immune system.
Immune-stimulatory compounds may have or cause antigenic specificity. In certain embodiments, an immune-stimulatory compound activates macrophages. In certain embodiments, an immune-stimulatory compound induces the secretion of cytokines by an antigen presenting cell. The increased activity or activation of the immune system may be evaluated using methods known in the field for evaluating an immune response (see, for example, J. Gratama, Cytometry A. 2008 Nov: 73(11): 971-4, the contents of which are incorporated herein in its entirety).
[0078] A "protein active site" as described herein, refers to a region of a protein target where a molecule (such as a substrate molecule or allosteric effector) binds to the target protein. The molecule may trigger a response upon binding to the the binding protein, e.g., inhibition of the activity of the binding protein or degradation of the binding protein. The protein active site includes the residues that interact with, e.g., bind covalently or non-covalently, a molecule such as an immune-stimulatory compound or a portion thereof. The protein active site may define a groove or pocket in the target protein wherein the interface between the groove or pocket and surrounding solvent is the solvent/active site interface of the protein active site.
[0079] The phrase "stimulate an immune response" refers to stimulating a response from immune cells that increases the activity or responsiveness of the immune system or a part thereof, such as, for example, inducing secretion of cytokines and/or chemokines, activating immune cells, e.g., T cells, B cells, macrophages, dendritic cells, etc., enhancing antigen presenting cell presentation of antigen, inducing antibody-dependent cell-mediated phagocytosis (ADCP), inducing antibody-dependent cell-mediated cytotoxicity (ADCC), NK cell or CD8+
T cell cytolytic activity, and/or blocking immune suppression.
[0080] As used herein, "homologous" or "homology" refer to the similarity or identity between a DNA, RNA, nucleotide, amino acid, or protein sequence to another DNA, RNA, nucleotide, amino acid, or protein sequence, respectively. Homology can be expressed in terms of a percentage of sequence identity of a first sequence to a second sequence.
Percent (%) sequence identity with respect to a reference DNA sequence is the percentage of DNA
nucleotides in a candidate sequence that are identical with the DNA nucleotides in the reference DNA sequence after aligning the sequences and introducing gaps, as necessary. Percent (%) sequence identity with respect to a reference amino acid sequence is the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference amino acid sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity.
[0081] As used herein, the abbreviations for the natural 1-enantiomeric amino acids are conventional and can be as follows: alanine (A, Ala); arginine (R, Arg);
asparagine (N, Asn);
aspartic acid (D, Asp); cysteine (C, Cys); glutamic acid (E, Glu); glutamine (Q, Gln); glycine (G, Gly); histidine (H, His); isoleucine (I, Ile); leucine (L, Leu); lysine (K, Lys); methionine (M, Met); phenylalanine (F, Phe); proline (P, Pro); serine (S, Ser); threonine (T, Thr); tryptophan (W, Trp); tyrosine (Y, Tyr); valine (V, Val). Unless otherwise specified, X can indicate any amino acid. In some aspects, X can be asparagine (N), glutamine (Q), histidine (H), lysine (K), or arginine (R).
[0082] As used herein, the term "antibody" refers to an immunoglobulin molecule that specifically binds to, or is immunologically reactive toward, a specific antigen. The term antibody can include, for example, polyclonal, monoclonal, genetically engineered, and antigen binding fragments thereof. An antibody can be, for example, murine, chimeric, humanized, bispecific, a heteroconjugate, a diabody, a triabody, a tetrabody or a hcAb (heavy chain antibody). An antigen binding fragment can include, for example, a Fab', F(ab')2, Fab, Fv, rIgG, scFv, a single domain antibody, VHH, VNAR, sdAb, or nanobody.
[0083] As used herein, the term "antigen" refers to a molecule that can be bound by an antibody or a antibody construct. An antigen may elicit an immune response. An antigen can be a protein, polysaccharide, lipid, glycolipid or the like, which can be recognized by an antibody or an immune cell, such as a T cell or a B cell. Exposure of immune cells to one or more of these antigens can elicit a rapid cell division and differentiation response resulting in the formation of clones of the exposed T cells and B cells. B cells can differentiate into plasma cells which in turn can produce antibodies which selectively bind to the antigens.
[0084] As used herein, the terms "recognize," "bind," and "specifically bind"
refer to the specific association or specific binding between an antigen binding domain and a corresponding antigen, or an immune stimulatory compound and a protein, as compared to the non-specific association or non-specific binding of the antigen binding domain or immune-stimulatory compound with a non-target antigen or protein.
[0085] As used herein, a "tumor antigen" is an antigen that can be expressed by or is present on, a cancer cell, a neoplastic tumor cell and/or within a tumor microenvironment.
[0086] As used herein, an "antibody construct" refers to a construct that contains an antigen binding domain and an Fc domain.
[0087] As used herein, an "antigen binding domain" refers to an antigen binding domain from an antibody or from a non-antibody that can specifically bind to the antigen.
Antigen binding domains can be numbered when there is more than one antigen binding domain in a given conjugate or construct (e.g., first binding domain, second antigen binding domain, third antigen binding domain, etc.). Different antigen binding domains in the same conjugate or construct can target the same antigen or different antigens (e.g., first binding domain that can bind a tumor antigen, second antigen binding domain that can bind to a tumor antigen or an antigen presenting cell (APC) antigen, and third antigen binding domain that can bind an APC
antigen).
[0088] As used herein, a "Fe domain" is an Fc domain from an antibody or from a non-antibody that can bind to an Fc receptor.
[0089] As used herein, an "Fe null" refers to an Fc domain that exhibits weak to no binding to any of the Fcgamma receptors. In some embodiments, an Fc null domain or region exhibits a reduction in binding affinity (e.g., increase in Kd) to Fc gamma receptors of at least 1000-fold.
[0090] As used herein, a "target binding domain" refers to a construct that contains an antigen binding domain from an antibody or from a non-antibody that can bind to the antigen.
[0091] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from a variety of organic and inorganic counter ions well known in the art.
Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids.
Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. 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, salicylic acid, and the like. 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, aluminum, and the like. 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, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
In some embodiments, the pharmaceutically acceptable base addition salt is chosen from ammonium, potassium, sodium, calcium, and magnesium salts.
[0092] As used herein, "agonism" is the binding of a chemical to a receptor to induce a biological response. A chemical can be, for example, a small molecule, a compound, or a protein.
An agonist causes a response, an antagonist can block the action of an agonist, and an inverse agonist can cause a response that is opposite to that of the agonist. A
receptor can be activated by either endogenous or exogenous agonists.
[0093] The term "Cx_y" when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the term "Cx_yalkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from x to y carbons in the chain, including haloalkyl groups such as trifluoromethyl and 2,2,2-trifluoroethyl, etc.
[0094] The terms "Cx_yalkenyl" and "Cx_yalkynyl" refer to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively.
[0095] The term "carbocycle" as used herein refers to a saturated, unsaturated or aromatic ring in which each atom of the ring is carbon. Carbocycle includes 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. In an exemplary embodiment, an aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, is included in the definition of carbocyclic.
Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl.
[0096] The term "heterocycle" as used herein refers to a saturated, unsaturated or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include N, 0, Si, P, B, and S
atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings wherein at least one of the rings includes a heteroatom. In an exemplary embodiment, an aromatic ring, e.g., pyridyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, morpholine, piperidine or cyclohexene. The term "heteroaryl" includes aromatic single ring structures, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms.
The term "heteroaryl" also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is heteroaromatic, e.g., the other cyclic rings can be aromatic or non-aromatic carbocyclic, or heterocyclic. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like.
[0097] The term "substituted" refers to moieties having substituents replacing a hydrogen on one or more carbons or substitutable heteroatoms, e.g., NH, of the structure. It will be understood that "substitution" or "substituted with" includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group. As used herein, the term "substituted" is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms.
[0098] In some embodiments, substituents raay include any substituents described herein, for example: halogen, hydroxy, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazino (=N-NH2), -Rb-ORa, -Rb-OC(0)-Ra, -Rb-OC(0)-0Ra, -Rb-OC(0)-N(R1)2, -Rb-N(R1)2, -Rb-C(0)Ra, -Rb -C(0)0Ra, -Rb-C(0)N(R1)2, -Rb-0-12c-C(0)N(Ra)2, -Rb-N(Ra)C(0)0Ra, -Rb-N(R1)C(0)Ra, -Rb-N
(Ra)S(0)Ra (where t is 1 or 2), -Rb-S(0)tRa (where t is 1 or 2), -Rb-S(0)tORa (where t is 1 or 2), and -Rb-S(0)tN(R1)2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocyclo alkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(0)-Ra, -Rb-OC(0)-0Ra, -Rb-OC(0)-N(R1)2, -Rb_N(R1)2, _Rb_c(0)Ra, _Rb -C(0)0Ra, -Rb-C(0)N(R1)2, -Rb-0-12c-C(0)N(Ra)2, -Rb-N(Ra)C(0)0Ra, -Rb-N(R1)C(0)Ra, -Rb-N
(Ra)S(0)Ra (where t is 1 or 2), -Rb-S(0)tRa (where t is 1 or 2), -Rb-S(0)tORa (where t is 1 or 2) and -Rb-S(0)tN(R1)2 (where t is 1 or 2); wherein each Ra is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine (=N-NH2), -Rb-ORa, -Rb-OC(0)-Ra, -Rb-OC(0)-0Ra, -Rb-OC(0)-N(R1)2, -Rb_N(R1)2, _Rb_c(0)Ra, _Rb -C(0)0Ra, -Rb-C(0)N(R1)2, -Rb-0-12c-C(0)N(Ra)2, -Rb-N(Ra)C(0)0Ra, -Rb-N(R1)C(0)Ra, -Rb-N
(Ra)S(0)Ra (where t is 1 or 2), -Rb-S(0)tRa (where t is 1 or 2), -Rb-S(0)tORa (where t is 1 or 2) and -Rb-S(0)tN(R1)2 (where t is 1 or 2); and wherein each Rb is independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each Rc is a straight or branched alkylene, alkenylene or alkynylene chain.
[0099] It will be understood by those skilled in the art that substituents can themselves be substituted, if appropriate. Unless specifically stated as "unsubstituted,"
references to chemical moieties herein are understood to include substituted variants. For example, reference to a "heteroaryl" group or moiety implicitly includes both substituted and unsubstituted variants.
[0100] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z- or E- form (or cis- or trans- form). Furthermore, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, chemical entities described herein are intended to include all Z-, E- and tautomeric forms as well.
[0101] A "tautomer" refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric y H
\\.
\11\r\
H H
\

N., NH2 \ NH v A )1/2,N
csss.N ciss H rrjS iSSS
ssi\J,N Ns N N HN N NN' ' csss N
OH
equilibrium include: N 0
[0102] The compounds, constructs and conjugates disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of 2H, 3H, 11,,, '3C and/or 14C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos.
5,846,514 and 6,334,997, or as otherwise known in the art. As described in U.S. Patent Nos.
5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs.
[0103] Unless otherwise stated, structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms.
For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13C- or 14C-enriched carbon are within the scope of the present disclosure.
[0104] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium (2H), tritium (3H), iodine-125 (1251) or carbon-14 (..,) Isotopic substitution with 2H, HC, 13C, 14C, 15C, 12N, 13N, 15N, 16N, 160, 170, 14F, 15F, 16F, 17F, 18F, 33s, 34s, 35s, 36¨, S 35C1, 37C1, 79Br, 81Br, and 1251 are all contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.
[0105] In certain embodiments, the compounds disclosed herein have some or all of the 1H atoms replaced with 2H atoms. The methods of synthesis for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.
[0106] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm.
Des., 2000;
6(10)[ 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony.
Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.
[0107] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein or otherwise known to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co.
[0108] Compounds also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof.
[0109] The phrases "parenteral administration" and "administered parenterally"
as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.
[0110] The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
[0111] The phrase "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt;
(6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid;
(16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol;
(20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.
[0112] As used herein, "attached" refers to a covalent bond, between two or more groups.
Alternatively, attached may refer to the connection of two or more groups via a linker, e.g., a linker connecting a second binding domain to an antibody construct. A fusion may refer to a nucleic acid sequence of two separate domains being expressed in frame. For example, a binding domain can be attached as a fusion or by attachment (e.g., conjugation) via a linker to an antibody construct or other portion of a conjugate. For example, an antibody can be fused with an additional binding domain to create an antibody construct containing a fusion of the antibody and the additional binding domain. The antibody construct can be the result of the nucleic acid sequence of the binding domain being expressed in frame with the nucleic acid sequence of the antibody construct. The fusion can be the result of an in-frame nucleotide sequence encoding the antibody construct with the binding domain. As another example, an additional binding domain can be attached to an antibody construct via a linker, wherein the linker is attached (i.e., conjugated) to the binding domain and the linker is attached to the antibody construct. The binding domain can be linked to the linker by a chemical conjugation and the antibody construct can be linked to the linker by a chemical conjugation. The additional binding domain can be a second binding domain and/or a third binding domain as described herein.
Furthermore, a binding domain can be a first binding domain attached to an Fc domain to produce the antibody construct as described herein, which may produce the first binding domain as a fusion with the Fc domain or a conjugate wherein the first binding domain can be linked to a linker and the linker can be linked to the Fc domain.
Immune-Stimulatory Conjugates
[0113] Disclosed herein are conjugates of antibody constructs, immune-stimulatory compounds and linkers, referred to as antibody construct-immune-stimulatory compound conjugates (also referred to as immune-stimulatory compound-conjugates, antibody conjugates or conjugates).
The conjugates may be used in the treatment of various diseases and disorders, including cancers.

Also disclosed pharmaceutical compositions of the conjugates. In certain embodiments, immune-stimulatory compounds are attached either directly or through a linker to an antibody construct to form antibody construct-immune-stimulatory compound conjugates.
[0114] In some embodiments, the immune-stimulatory compound stimulates the immune system, or a component thereof. In some embodiments, the immune-stimulatory compound has an immune-modulatory activity. In some embodiments, the immune-stimulatory compound has an inhibitory effect on a component of the immune system, thereby stimulating an immune-modulatory activity.
[0115] In certain embodiments, conjugates are represented by the following formula:
_ A
. Dx \
/n - z , wherein A is an antibody construct, L is a linker, D is an immune-stimulatory compound, x may be from 1 to 20 (wherein each x denotes a separate compound), n may be from 1 to 20, and z may be from 1 to 20. In some embodiments, L is a cleavable linker. In some embodiments, L is a non-cleavable linker.
[0116] In some embodiments, x is 1, n is 1 and z may be from 1 to 10, such as from 1 to 9, such as from 1 to 8, such as from 2 to 8, such as from 1 to 6, such as from 3 to 5 or such as about 2.
[0117] In some embodiments, x is 1, n is 2, and z may be from 1 to 10, such as from 1 to 9, such as from 1 to 8, such as from 2 to 8, such as from 1 to 6 or such as from 3 to 5. In certain embodiments, z is 4.
[0118] In some embodiments, x may be from 1-20, n may be from 1-20, and z may be from 1 to 20.
[0119] In certain embodiments, conjugates are represented by the following formula:
_ A
. Dx \
/n - z , wherein A is an antibody construct, L is a linker having the structure -Aa-Ww-Yy-, where A is a spacer, a is 0 or 1, W is a cleavable unit, w may be from 0 to 10, Y is a stretcher, y may be from 0 to 3, D is an immunomodulatory compound, x may be from 1 to 20 (wherein each x denotes a distinct compound), n may be from 1 to 20, and z may be from 1 to 20.
[0120] In some embodiments, a is 1, w is 0, y is 0, x is 1, n is 1, and z may be from 1 to 20, 1 to 10, 1 to 9, 1 to 8, 2 to 8, 1 to 6 or 3 to 5. In certain embodiments, z is 4.
[0121] In some embodiments, a isl, w is 1, y is from 1, xis 1, n is 1 and z may be from 1 to 10, 1 to 9, 1 to 8, 2 to 8, 1 to 6, 3 to 5, 2 or 4.
[0122] In some embodiments, a is 0 or 1, w is from 0 to 10, y is from 0-3, where at least one of a, w or y is present, x may be from 1 to 20, n may be from 1-20, and z may be from 1 to 20.
[0123] In some embodiments, the immune-stimulatory conjugates include a linker (L) that may comprise from 5 to 100 linear non-hydrogen atoms that is covalently attached to an antibody construct (A) and may be:
i) covalently attached to an immune-stimulatory compound (C1) as in the following formula:
A _________________________________ ii) covalently attached to an immune-stimulatory compound (C1) which itself may be covalently attached to a spacer (S) comprising from 5 to 100 linear non-hydrogen atoms covalently attached to a second immune-stimulatory compound (C2) as in the following formula:
A
iii) covalently attached an immune-stimulatory compound (C2) that may be covalently attached to a spacer (S) comprising from 5 to 100 linear non-hydrogen atoms covalently attached to a first immune-stimulatory compound (C1) as in the following formula:
A
iv) covalently attached to a spacer (S) comprising from 5 to100 linear non-hydrogen atoms that is covalently attached immune-stimulatory compounds (C1 and C2) as in the following formula:
A
= = =
= .
[0124] In some embodiments, an immune-stimulatory conjugate is provided that includes a proteolysis targeting module (PTM; also referred to as a proteolysis-targetting chimera or PROTAC) that includes an immune-modulatory compound (IMC) that is covalently attached to an E3 ubiquitin ligase binding moiety (ULM) through a spacer (S) and wherein a linker (L) is covalently attached to the protein targeting molecule and to the antibody construct (0), as represented by the formula <>-(L-PTM), where n is from 1-20 and z is from 1 to 20. In some embodiments, L is a cleavable linker. In some embodiments, S is a non-cleavable spacer.
[0125] Referring to the previous formula, in some embodiments, C1 is a target protein targeting moiety, such as an immodulatory compound, C2 is an E3 ubiquitin ligase binding moiety such that together C1-S-C2 may form a PTM.
[0126] In some embodiments, an immune-modulatory compound or other protein targeting moiety (IMC) is covalently attached to an E3 ubiquitin ligase binding moiety (ULM) through a spacer (S) and a linker (L) is covalently attached to the spacer, n is from 1-20 and z is from 1 to 20 as represented by the formula:
= * 40 .
\ -te
[0127] In some embodiments, L is a cleavable linker. In some embodiments, L is a non-cleavable linker. In some embodiments, S is non-cleavable.
[0128] In some embodiments, an immune-modulatory compound or other protein targeting moiety (IMC) is covalently attached to an E3 ubiquitin ligase binding moiety (ULM) through a spacer (S) and a linker (L) is covalently attached to the IMC, n is from 1-20 and z is from 1 to 20 as represented by the formula:
_ A
. . .
[0129] In some embodiments, L is a cleavable linker. In some embodiments, L is a non-cleavable linker.
[0130] In some embodiments, an immune-modulatory compound or other protein targeting moiety (IMC) is covalently attached to an E3 ubiquitin ligase binding moiety (ULM) through a spacer (S) and linker L is covalently attached to the ubiquitin E3 ligase moiety (ULM), n is from 1-20 and z is from 1 to 20 as represented by the formula:
_ \ -A . 4) 6 .
_
[0131] In some embodiments, L is a cleavable linker. In some embodiments, L is a non-cleavable linker. In some embodiments, S is non-cleavable.
Tumor and Immune Cell Antigens
[0132] In cancer, there are several general groups of tumor antigens, including but not limited to:
(i) viral tumor antigens which can be identical for any viral tumor of this type, (ii) carcinogenic tumor antigens which can be specific for patients and for the tumors, (iii) isoantigens of the transplantation type or tumor-specific transplantation antigens which can be different in all individual types of tumor but can be the same in different tumors caused by the same inciting biological event; and (iv) embryonic antigens.
[0133] As a result of the discovery of tumor antigens, tumor antigens have become important in the development of new cancer treatments that can specifically target the cancer. This has led to the development of antibodies directed against these tumor antigens. Such tumor antigens include the following: CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV E7, Her-2/neu, p53 nonmutant, NY-ES0-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page 4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, and gpNMB.
[0134] In addition to the development of antibodies against tumor antigens for cancer treatment, antibodies that target immune cells to boost the immune response have also been developed, including the following: an anti-CD40 antibody, an anti-CD47 antibody, anti-TNFR2 antibody, an anti-DEC205 antibody, an anti-CD36 mannose scavenger receptor 1 antibody, an anti-CLEC9A antibody, an anti-CLEC12A antibody, an anti-DC-SIGN antibody, an anti-antibody, an anti-OX4OL antibody, an anti-41BBL antibody, an anti-CD204 antibody, an anti-MARCO antibody, an anti-CLEC5A antibody, an anti-Dectin 1 antibody, and anti-Dectin 2 antibody, an anti-CLEC10A antibody, an anti-CD206 antibody, an anti-CD64 antibody, an anti-CD32A antibody, an anti-CD16A antibody, an anti-HVEM antibody, an anti-CD38 antibody, an anti-PD-Li antibody, an anti-TREM2 antibody, an anti-CSF1R antibody, or an anti-CD32B
antibody can be used to target, respectively, cell surface CD40, CD47, TNFR2, DEC-205, CD36 mannose scavenger receptor 1, CLEC9A, CLEC12A, DC-SIGN, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, CD38, PD-L1, TREM2, CSF1R, or CD32B molecules expressed by antigen presenting cells.
[0135] Cluster of Differentiation 40 (CD40) is a member of the Tumor Necrosis Factor Receptor (TNF-R) family. CD40 can be a 50 kDa cell surface glycoprotein that can be constitutively expressed in normal cells, such as monocytes, macrophages, B lymphocytes, dendritic cells, endothelial cells, smooth muscle cells, fibroblasts and epithelium, and in tumor cells, including B-cell lymphomas and many types of solid tumors. Expression of CD40 can be increased in antigen presenting cells in response to IL-13p, IFN-y, GM-CSF, and LPS induced signaling events.
[0136] Examples of agonistic CD40 monoclonal antibodies include CP-870,893, dacetuzumab, Chi Lob 7/4, SEA-CD40, ADC-1013, 3C3, or 3G5.
[0137] Cluster of Differentiation 205 (CD205 or DEC-205) is a member of the C-type multilectin family of endocytic receptors, which can include the macrophage mannose receptor (MMR) and the phospholipase A2 receptor (PLA2R). DEC-205 can be a 205 kDa endocytic receptor highly expressed in cortical thymic epithelial cells, thymic medullary dendritic cells (CD11c+ CD8+), subpopulations of peripheral dendritic cells (CD11c+ CD8+). The DEC-205+
CD11c+ CD8+ dendritic cells (DCs) can function in cross-presentation of antigens derived from apoptotic cells. Additionally, DEC-205 can be significantly upregulated during DC maturation.
DEC-205 can also be expressed at moderate levels in B cells and low levels in macrophages and T cells.
[0138] After antigen binding to DEC-205, the receptor-antigen complex can be internalized whereupon the antigen can be processed and be presented on the DC surface by a major histocompatibility complex class II (MHC II) or MHC class I. DEC-205 can deliver antigen to DCs for antigen presentation on MHC class II and cross-presentation on MHC
class I. DEC-205 mediated antigen delivery for antigen presentation in DCs without an inflammatory stimulus can result in tolerance. Conversely, DEC-205 mediated antigen delivery in DCs in the presence of a maturational stimulus (e.g., a CD40 agonist) can result in long-term immunity via activation of antigen-specific CD4+ and CD8+ T cells.
[0139] CD36 mannose scavenger receptor 1 is an oxidized LDL receptor with two transmembrane domains located in the caveolae of the plasma membrane. It can be classified as a Class B scavenger receptor, which can be characterized by involvement in the removal of foreign substances and waste materials. This receptor can also be involved in cell adhesion, phagocytosis of apoptotic cells, and metabolism of long-chain fatty acids.
[0140] TNFR2 (tumor necrosis factor receptor 2), also known as TNFRSF1B (tumor necrosis factor receptor super family 1B) and CD120b, is a single-pass type I membrane protein and the member of TNFR superfamily containing 4 cysteine-rich domains (CRD) repeats.
In addition to the full length membrane-anchored form, soluble TNFR2 can be generated via two distinct mechanisms: (1) shedding via proteolytic processing of the full membrane anchored from, and (2) translation from an alternatively spliced message encoding the extracellular domains of TNFR2. TNFR2 is the receptor with high affinity for TNF-alpha and approximately 5-fold lower affinity for homotrimeric lymphotoxin-alpha. TNFR2 (Tumor Necrosis Factor Receptor Type II) and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. c-IAP1 can potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice suggest a role of TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways.
[0141] CLEC9A is a group V C-type lectin receptor. This receptor can be expressed as on myeloid lineage cells, and can be characterized as an activation receptor.
[0142] CLEC12A is a member of the C-type lectin/C-type lectin like domain super family that can be a negative regulator of granulocyte and monocyte function. It can also be involved in cell adhesion, cell-cell signaling, and glycoprotein turnover, and can play a role in the inflammatory response.
[0143] Dendritic cell-specific inter cellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) or CD209, is a C-type lectin receptor that can be expressed on the surface of macrophages and dendritic cells. This receptor can recognize and bind to mannose type carbohydrates and be involved in activating phagocytosis, can mediate dendritic cell rolling, and can be involved in CD4+ T cell activation.
[0144] BDCA-2 is a C-type lectin that is a membrane protein of plasmacytoid dendritic cells. It can be involved in plasmacytoid dendritic cell function, such as ligand internalization and presentation.
[0145] OX4OL, which is also referred to as CD252, is the ligand for CD134 that can be expressed on dendritic cells. It can be involved in T cell activation.
[0146] 41BBL, which is also referred to as CD137L, is a member of the TNF
superfamily, and can be expressed on B cells, dendritic cells, activated T cells, and macrophages. It can provide co-stimulatory signal for T cell activation and expansion.
[0147] CD204, which is also referred to as macrophage scavenger receptor 1, is a macrophage scavenger receptor receptor. The gene for CD204 can encode three different class A macrophage scavenger receptor isoforms. The type 1 and type 2 isoforms can be involved in binding, internalizing, and processing negatively charged macromolecules, such as low density lipoproteins. The type 3 isoform can undergo altered intracellular processing in which it can be retained within the endoplasmic reticulum, and has been shown to have a dominant negative effect on the type 1 and type 2 isoforms.
[0148] Macrophage receptor with collagenous structure (MARCO), which is also referred to as SCARA2, is a class A scavenger receptor with collagen-like and cysteine-rich domains. It can be expressed in macrophages, and can bind to modified low density lipoproteins.
It can be involved in the removal of foreign substances and waste materials.
[0149] C-type lectin domain family 5 member A (CLEC5A) is a C-type lectin. It can be involved in the myeloid lineage activating pathway.
[0150] Dendritic cell-associated c-type lectin-1 (Dectin 1), which is also referred to as CLEC7A, is member of the C-type lectin/C-type lectin-like super family. It can be expressed by myeloid dendritic cells, monocytes, macrophages, and B cells, and can be involved in antifungal immunity.
[0151] Dendritic cell-associated c-type lectin-2 (Dectin 2), which is also referred to as CLEC6A, is member of the C-type lectin/C-type lectin-like super family. It can be expressed by dendritic cells, macrophages, monocytes and neutrophils. It can be involved in antifungal immunity.
[0152] CLEC10A, which is also referred to as CD301, is member of the C-type lectin/C-type lectin-like super family. It can be expressed by dendritic cells, monocytes, and CD33+ myeloid cells, and can be involved in macrophage adhesion and migration.
[0153] CD206, which is also referred to as macrophage mannose receptor, is a C-type lectin type I membrane glycoprotein. It can be expressed on dendritic cells, macrophages and endothelial cells, and can act as a pattern recognition receptor and bind high-mannose structures of viruses, bacteria, and fungi.
[0154] CD64, which is also referred to as FcyRI, is a high affinity Fc receptor for IgG. It can be expressed by monocytes and macrophages. It can be involved in mediating phagocytosis, antigen capture, and antibody dependent cell-mediated cytoxicity.
[0155] CD32A, which is also referred to as FcyRIIa, is a low affinity Fc receptor. It can be expressed on monocytes, granulocytes, B cells, and eosinophils. It can be involved in phagocytosis, antigen capture, and antibody dependent cell-mediated cytoxicity.
[0156] CD16A, which is also referred to as FcyRIIIa, is low affinity Fc receptor. It can be expressed on NK cells, and can be involved in phagocytosis and antibody dependent cell-mediated cytotoxicity.
[0157] Herpesvirus entry mediator (HVEM), which is also referred to as CD270, is a member of the TNF-receptor superfamily. It can be expressed on B cells, dendritic cells, T cells, NK cells, CD33+ myeloid cells, and monocytes. It can be involved in activating the immune response.
[0158] CD32B, which is also referred to as FcyRIIb, is a low affinity Fc receptor. It can be expressed on B cells and myeloid dendritic cells. It can be involved in inhibiting maturation and cell activation of dendritic cells.
[0159] The HER2/neu (human epidermal growth factor receptor 2/receptor tyrosine-protein kinase erbB-2) is part of the human epidermal growth factor family.
Overexpression of this protein can be shown to play an important role in the progression of cancer, for example, breast cancer. The HER2/neu protein can function as a receptor tyrosine kinase and autophosphorylates upon dimerization with binding partners. HER2/neu can activate several signaling pathways including, for example, mitogen-activated protein kinase, phosphoinositide 3-kinase, phospholipase Cy, protein kinase C, and signal transducer and activator of transcription (STAT).
Examples of antibodies that can target and inhibit HER2/neu can include trastuzumab and pertuzumab.
[0160] EGFR (epidermal growth factor receptor) encodes a member of the human epidermal growth factor family. Mutations that can lead to EGFR overexpression or over activity can be associated with a number of cancers, including squamous cell carcinoma and glioblastomas.
EGFR can function as a receptor tyrosine kinase and ligand binding can trigger dimerization with binding partners and autophosphorylation. The phosphorylated EGFR can then activate several downstream signaling pathways including mitogen-activated protein kinase, phosphoinositide 3-kinase, phospholipase Cy, protein kinase C, and signal transducer and activator of transcription (STAT). Examples of antibodies that can target and inhibit EGFR can include cetuximab, panutumumab, nimotuzumab, and zalutumumab. One mutant variant of EGFR is EGFRvIII
(epidermal growth factor receptor variant III, also referred to as de2-7EGFR).
EGFRvIII is the result of an EGFR gene rearrangement in which exons 2-7 of the extracellular domain are deleted. This mutation can result in a mutant receptor incapable of binding to any known ligand.
The resulting receptor can engage in a constitutive low-level signaling and can be implicated in tumor progression. Examples of antibodies that can target EGFRvIII can include AMG595 and ABT806.
[0161] C-Met (hepatocyte growth factor receptor) encodes a member of the receptor tyrosine kinase family of proteins. C-Met overexpression and over activity can be implicated in various cancers including lung adenocarcinomas, and high c-Met levels can be associated with poor patient outcome. Binding of hepatocyte growth factor can induce dimerization and autophosphorylation of c-Met. The c-Met receptor can activate various downstream signaling pathways including mitogen-activated protein kinase, phosphoinositide 3-kinase, and protein kinase C pathways. The antibody onartuzumab can target and inhibit c-Met.
[0162] HER3 (human epidermal growth factor receptor 3) encodes a member of the human epidermal growth factor receptor family. Ligand binding can induce dimerization and autophosphorylation of cytoplasmic tyrosine residues that then can recruit signaling proteins for downstream signaling pathway activation including mitogen-activated protein kinase and phosphoinoside 3-kinase pathways. HER3 can play an active role in cell proliferation and survival, and can be overexpressed, overactive, and/or mutated in various cancers. For example, HER3 can be overexpressed in breast, ovarian, prostate, colon, pancreas, stomach, oral, and lung cancers. The antibody patritumab can target and inhibit HER3.
[0163] MUC1 (mucin 1, cell surface associated) encodes a member of the mucin family of glycosylated proteins that can play an important role in cell adhesion and forming protective mucosal layers on epithelial surfaces. MUC1 can be proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex with the N-terminal alpha subunit providing cell-adhesion functionality and the C-terminal beta subunit modulating cell signaling pathways including the mitogen activated map kinase pathway. MUC1 can play a role in cancer progression, for example, by regulating TP53-mediated transcription. MUC1 overexpression, aberrant intracellular localization, and glycosylation changes can all be associated with carcinomas including pancreatic cancer cells. The antibody clivatuzumab can target MUC1.
[0164] MUC16 (mucin 16, cell surface associated) encodes the largest member of the mucin family of glycosylated proteins that can play an important role in cell adhesion and forming protective mucosal layers on epithelial surfaces. MUC16 can be a highly glycosylated 2.5MDa transmembrane protein that can provide a hydrophilic lubricating barrier on epithelial cells. The cytoplasmic tail of MUC16 can be involved with various signaling pathways including the JAK2-STAT3 and Src kinase pathways. A peptide epitope of MUC16 can be used as biomarker for detecting ovarian cancer. Elevated expression of MUC16 can be present in advanced ovarian cancers and pancreatic cancers. The antibody sofituzumab can target MUC16.
[0165] EPCAM (epithelial cell adhesion molecule) encodes a transmembrane glycoprotein that can be frequently and highly expressed in carcinomas and tumor-initiating cells. EPCAM can also be a pluripotent stem cell marker. EPCAM can modulate a variety of pathways including cell-cell adhesion, cellular proliferation, migration, invasion, maintenance of a pluripotent state, and differentiation in the context of tumor cells. The antibodies edrecolomab and adecatumumab can target EPCAM.
[0166] MSLN (mesothelin) encodes a 40 kDa cell GPI-anchored membrane surface protein believed to function in cell adhesion. MSLN is overexpressed in mesothelioma and certain types of pancreatic, lung, and ovarian cancers. MSLN-related peptides that circulate in serum of patients suffering from pleural mesothelioma are used as biomarkers for monitoring the disease.
MSLN may promote metastasis by inducing matrix metalloproteinase 7 and 9 expression. The monoclonal antibody anetumab has been developed to target MSLN.
[0167] CA6 (carbonic anhydrase VI) encodes one of several isozymes of carbonic anhydrase.
CA6 is found in salivary glands and may play a role in the reversible hydration of carbon dioxide. CA6 is expressed in human serous ovarian adenocarcinomas. The monoclonal antibody huDS6 has been developed to target CA6.
[0168] NAPI2B (sodium/phosphate cotransporter 2B) encodes a type II sodium-phosphate cotransporter. NAPI2B is highly expressed on the tumor surface in lung, ovarian, and thyroid cancers as well as in normal lung pneumocytes. The monoclonal antibody lifastuzumab has been developed to target NAPI2B.
[0169] TROP2 (trophoblast antigen 2) encodes a transmembrane glycoprotein that acts as an intracellular calcium signal transducer. TROP2 binds to multiple factors such as IGF-1, claudin-1, claudin-7, cyclin D1, and PKC. TROP2 including intracellular calcium signaling and the mitogen activated protein kinase pathway. TROP 2 plays a role in cell self-renewal, proliferation, invasion, and survival. Discovered first in trophoblast cells that have the ability to invade uterine decidua during placental implantation, TROP2 overexpression has been shown to be capable of stimulating cancer growth. TROP2 overexpression has been observed in breast, cervix, colorectal, esophagus, lung, non-Hodgkin's lymphoma, chronic lymphocytic lymphoma, Raji Burkitt lymphoma, oral squamous cell, ovarian, pancreatic, prostate, stomach, thyroid, urinary bladder, and uterine carcinomas. The monoclonal antibody sacituzumab has been developed to target TROP2.
[0170] CEA (carcinoembryonic antigen; also referred to as CEACAM5) is a member of a family of related glycoproteins involved in cell adhesion. CEA is a biomarker for gastrointestinal cancers and may promote tumor development by means of its cell adhesion function. CEA levels have been found to be elevated in serum of individuals with colorectal carcinoma. CEA levels have also been found to be elevated in gastric carcinoma, pancreatic carcinoma, lung carcinoma, breast carcinoma, and medullary thyroid carcinoma. The monoclonal antibodies PR1A3 and Ab2-3 have been developed to target CEA.
[0171] CLDN18.2 (claudin 18) encodes a member of the claudin family of integral membrane proteins. CLDN18.2 is a component of tight junctions that create a physical barrier to prevent diffusion of solutes and water through the paracellular space between epithelial cells. CLDN18.2 is overexpressed in infiltrating ductal adenocarcinomas, but is reduced in some gastric carcinomas. The monoclonal antibody claudiximab has been developed to target CLDN18.2.
[0172] FAP (fibroblast activation protein, alpha) encodes a homodimeric integral membrane protein from a family of serine proteases. FAP is believed to play a role in many processes including tissue remodeling, fibrosis, wound healing, inflammation, and tumor growth. FAP
enhances tumor growth and invasion by promoting angiogenesis, collagen fiber degradation and apoptosis, and by downregulating the immune response. FAP is selectively expressed on fibroblasts within the tumor stroma. The monoclonal antibody sibrotuzumab has been developed to target FAP.
[0173] EphA2 (EPH Receptor A2) encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EphA2 binds to ephrin-A ligands. Activation of EphA2 receptor upon ligand binding can result in modulation of migration, integrin-mediated adhesion, proliferation, and differentiation. EphA2 is overexpressed in various cancers including breast, prostate, urinary bladder, skin, lung, ovarian, and brain cancers. High EphA2 expression is also correlated with poor prognosis. The monoclonal antibodies DS-8895a optl, DS-8895 opt2, and the 1C1 antibody in MEDI-547 have been developed to target EphA2.
[0174] RON (macrophage stimulating 1 receptor) encodes a cell surface receptor for macrophage stimulating protein (MSP) with tyrosine kinase activity and belongs to the MET
proto-oncogene family. RON has significant structural similarity and sequence identity with the cancer-related gene C-MET. RON plays a significant role in KRAS oncogene addiction and has also been shown to be overexpressed in pancreatic cancers. Altered Ron expression and activation has been associated with decreased survival and cancer progression in various cancers including gastric, colon, breast, bladder, renal cell, ovarian, and hepatocellular cancers. The monoclonal antibody narnatumab has been developed to target RON.
[0175] LY6E (lymphocyte antigen 6 complex, locus E) encodes an interferon alpha-inducible GPI-anchored cell membrane protein. LY6E is overexpressed in numerous cancers including lung, gastric, ovarian, breast, kidney, pancreatic, and head and neck carcinomas. The monoclonal antibody in RG7841 has been developed to target LY6E.
[0176] FRA (folate receptor alpha) encodes a GPI-anchored cell surface glycoprotein. FRA binds folic acid, a molecule needed for cell growth and DNA synthesis, and mediates its internalization via receptor-mediated endocytosis. FRA is overexpressed in various cancers including prostate, breast, ovarian, pancreatic, mesothelioma, non-small cell lung carcinoma, and head and neck cancer. FRA expression has also been found to enhance tumor cell proliferation. The monoclonal antibodies farletuzumab and mirvetuximab have been developed to target FRA.
[0177] PSMA (prostate specific membrane antigen) is a type II transmembrane glycoprotein belonging to the M28 peptidase family that is expressed in all types of prostate tissues. PSMA is upregulated in cancer cells within the prostate and is used as a marker for prostate cancer. PSMA
expression may also serve as a predictor of disease recurrence in prostate cancer patients. The monoclonal antibodies J591 variant 1 and J591 variant 2 have been developed to target PSMA.
[0178] DLL3 (delta-like 3) encodes a ligand in the Notch signaling pathway that is associated with neuroendocrine cancer. DLL3 is most highly expressed in the fetal brain and is involved in somitogenesis in the paraxial mesoderm. DLL3 is expressed on tumor cell surfaces but not in normal tissues. The monoclonal antibody rovalpituzumab has been developed to target DLL3.
[0179] PTK7 (tyrosine protein kinase-like 7) encodes a receptor tyrosine kinase that lacks catalytic tyrosine kinase activity but is nevertheless capable of signal transduction. PTK7 interacts with the WNT signaling pathway, which itself has important roles in epithelial mesenchymal transition and various cancers such as breast cancer. PTK7 overexpression has been associated with patient prognosis depending on the cancer type. The monoclonal antibodies in PF-06647020 and the anti-PTK7 antibody described by SEQ ID NOs: 440 and 445 have been developed to target PTK7.
[0180] LIV1 (LIV-1 protein, estrogen regulated) encodes a member of the LIV-1 subfamily of ZIP (Zrt-, Irt-like proteins) zinc transporters. LIV1 is an estrogen regulated protein that transports zinc and/or other ions across the cell membrane. Elevated levels of LIV1 have been shown in estrogen receptor positive breast cancers, and LIV1 is used as a marker of ER-positive cancers.
LIV1 has also been implicated as a downstream target of the STAT3 transcription factor and as playing an essential role in the nuclear localization of the Snail transcription factor that modulates epithelial-to-mesenchymal transition. The monoclonal antibody in SGN-LIV1A has been developed to target LIV1.
[0181] ROR1 (receptor tyrosine kinase-like orphan receptor 1) encodes a member of the ROR
family of orphan receptors. ROR1 has been found to bind Wnt5a, a non-canonical Wnt via a Frizzled domain (FZD), and plays an important role in skeletal, cardiorespiratory, and neurological development. ROR1 expression is predominantly restricted to embryonic development and is absent in most mature tissues. In contrast, ROR1 expression is upregulated in B-Cell chronic lymphocytic leukemia, acute lymphocytic leukemia, non-Hodgkin lymphoma, and myeloid malignancies. The monoclonal antibody cirmtuzumab has been developed to target ROR1.
[0182] MAGE-A3 (melanoma-associated antigen 3) encodes a member of the melanoma-associated antigen gene family. The function of MAGE-A3 is not known, but its elevated expression has been observed in various cancers including melanoma, non-small cell lung cancer, and in putative cancer stem cell populations in bladder cancer. The monoclonal antibody described by SEQ ID NOs: 479 and 484 has been developed to target MAGE-A3.
[0183] NY-ESO-1 (New York esophageal squamous cell carcinoma 1) encodes a member of the cancer-testis family of proteins. Cancer-testis antigen expression is normally restricted to testicular germ cells in adult tissues, but has been found to be aberrantly expressed in various tumors including soft tissue sarcomas, melanoma, epithelial cancers, and myxoid and round cell liposarcomas. The monoclonal antibody described by SEQ ID Nos: 492 and 497 has been developed to target NY-ESO-1.
Binding Domain
[0184] The binding domain of an antibody construct is selected to recognize an antigen or molecule. For example, an antigen can be a cell surface marker on target cells associated with a disease or condition. An antigen can be a peptide or fragment thereof. An antigen can be expressed on an immune cell. An antigen can be expressed on an antigen-presenting cell. An antigen can be expressed on a dendritic cell, a macrophage, or a B cell. An antigen on an antigen presenting cell can be a cell lineage marker or a cell surface protein expressed preferentially on antigen presenting cells or a subset of antigen presenting cells. An antigen can be a peptide presented in a major histocompatibility complex by cell. As another example, a cell surface marker recognized by the antigen binding domain can include macromolecules associated with viral and bacterial diseases or infections, autoimmune diseases and cancerous diseases. An antigen can be a tumor antigen or fragment thereof. A tumor antigen can be any antigen listed on tumor antigen databases, such as TANTIGEN, or peptide databases for T cell-defined tumor antigens, such as the Cancer Immunity Peptide database. A tumor antigen can also be any antigen listed in the review by Chen (Chen, Cancer Immun 2004 [updated 2004 Mar 10;
cited 2004 Apr 1]). An antigen can be or can be at least 80% homologous CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII
(de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV E7, Her-2/neu, p53 nonmutant, NY-ES0-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page 4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2õ TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-(UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, or gpNMB.
[0185] In some embodiments, an antigen binding domain recognizes a single antigen. In some embodiments, an antigen binding domain recognizes two or more different antigens.
[0186] An antibody construct can include one or more binding domains. For example, an antibody construct can comprise a first binding domain. An antibody construct can also comprise a second binding domain. A binding domain can specifically bind to an antigen on a cell surface.
A binding domain can specifically bind to an antigen on a cell surface, for example, of a tumor or cancer cell, an immune cell, or of an antigen presenting cell, such as a dendritic cell or macrophage. A binding domain can be a cell surface receptor agonist. A binding domain can be an antigen binding domain. An antigen binding domain can be a cell surface receptor agonist. An antigen binding domain can be a domain that can specifically bind to an antigen. An antigen binding domain can specifically bind to a tumor antigen. An antigen binding domain can be an antigen-binding portion of an antibody or an antigen binding fragment thereof.
A binding domain can recognize a single antigen.
[0187] An antibody construct can include, for example, one, two, three, four, five, six, seven, eight, nine, ten, or more antigen binding domains. An antibody construct, such as an antibody, can include two antigen binding domains in which each antigen binding domain can recognize the same antigen. An antibody construct, such as a bi-specific antibody, can include two antigen binding domains in which each antigen binding domain can recognize different antigens. An antibody construct can include three antigen binding domains in which each antigen binding domain can recognize different antigens. An antibody construct can include three antigen binding domains in which two of the antigen binding domains can recognize the same antigen. An antigen binding domain can be in a scaffold, in which a scaffold is a supporting framework for the antigen binding domain. An antigen binding domain can be in a non-antibody scaffold. An antigen binding domain can be in an antibody scaffold. An antibody construct can comprise an antigen binding domain in a scaffold. The antibody construct can further comprise an Fc fusion protein product. In some embodiments, the antibody construct is an Fc fusion protein.
[0188] In some embodiments, an antibody construct can comprise an antigen binding domain that can specifically bind to a tumor antigen. A tumor antigen, also referred to as a tumor associated antigen, is an antigen that can be expressed by a cancer cell, a neoplastic tumor cell and/or within a tumor microenvironment. It is preferably not expressed or expressed at low levels on normal (non-cancerous) cells. For example, a tumor antigen can be an antigen expressed on a cell associated within a tumor, such as a neoplastic cell, or a tumor associated cell such as a stromal cell, endothelial cell, fibroblast, or tumor-infiltrating immune cell. For example, the tumor antigen Her2/Neu can be overexpressed by certain types of breast and ovarian cancer.
A tumor antigen can also be ectopically expressed by a tumor and contribute to deregulation of the cell cycle, reduced apoptosis, metastasis, or escape from immune surveillance. Tumor antigens can generally be proteins or polypeptides derived therefrom, but also can be glycans, lipids, or other small organic molecules. Additionally, a tumor antigen can arise through increases or decreases in post-translational processing exhibited by a cancer cell compared to a normal cell, for example, protein glycosylation, protein lipidation, protein phosphorylation, or protein acetylation.
[0189] In certain embodiments, a binding domain specifically can bind to a tumor associated antigen, such as CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1 antigen, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV E7, Her-2/neu, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, or gpNMB.
[0190] In some embodiments, a binding domain specifically can bind to a tumor associated antigen having at least 80%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity to CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1 antigen, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV
E7, Her-2/neu, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, MYCN, RhoC, TRP-2, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, CYP1B1, PLAV1, BORIS, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, or gpNMB.
[0191] In certain embodiments, a binding domain specifically binds to an antigen selected from the group consisting of comprising Her2/Neu (CD340), EGFR, CMET, HER3, MUC1, MUC16, EPCAM, MSLN, CA6, NAPI2B, TROP2, CEA, CLDN18.2, EGFRvIII, FAP, EphA2, RON, LY6E, FRA, PSMA, DLL3, PTK7, LIV1, ROR1, MAGE-A3, and NY-ESO-1.
[0192] A binding domain of an antibody construct can be selected from any domain that specifically binds to an antigen, including but not limited to, from a monoclonal antibody, a polyclonal antibody, a recombinant antibody, or a functional fragment thereof, for example, a heavy chain variable domain (VH) and a light chain variable domain (VL), or from a non-antibody such as a DARPin, an affimer, an avimer, a knottin, a monobody, an affinity clamp, an ectodomain, a receptor ectodomain, a receptor, a cytokine, a ligand, an immunocytokine, a T-cell receptor, a VNAR, an anticalin, or a recombinant T-cell receptor. In some embodiments, a binding domain of an antibody construct is from a monoclonal antibody, a polyclonal antibody, a recombinant antibody, or a functional fragment thereof, for example, a heavy chain variable domain (VH) and a light chain variable domain (VL).
[0193] The antigen binding domain of an antibody construct can be at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% homologous to an antigen binding domain selected from, but not limited to, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, or a functional fragment thereof, for example, a heavy chain variable domain (VH) and a light chain variable domain (VL), or from a non-antibody, such as a DARPin, an affimer, an avimer, a knottin, a monobody, an affinity clamp, an ectodomain, a receptor ectodomain, a receptor, a cytokine, a ligand, an immunocytokine, a T-cell receptor, a VNAR, an anticalin, or a recombinant T-cell receptor.
[0194] A binding domain, for example an antigen binding domain from a monoclonal antibody, can comprise a light chain and a heavy chain. In one aspect, the monoclonal antibody binds to an antigen present on the surface of an antigen presenting cell (APC antigen) and comprises the light chain of an anti-APC antigen antibody and the heavy chain of an anti-APC
antigen antibody, which bind an APC antigen. In another aspect, the monoclonal antibody binds to a tumor antigen comprises the light chain of a tumor antigen (anti-tumor) antibody and the heavy chain of a tumor antigen (anti-tumor) antibody, which bind to the tumor antigen.
[0195] An antibody construct can be an antibody. An antibody molecule can include of two identical light protein chains (light chains) and two identical heavy protein chains (heavy chains), all held together covalently by interchain disulfide linkages. Structurally, various functions of an antibody can be confined to discrete protein regions or domains. The sites that can recognize and can bind to antigen consist of three complementarity determining regions (CDRs; also referred to as hyper-variable regions) that lie within the variable heavy chain regions and within the variable light chain regions at the N-terminal ends of the two heavy and two light chains. The constant domains can provide the general framework of the antibody and may not be involved directly in binding the antibody to an antigen, but can be involved in various effector functions, such as participation of the antibody in antibody-dependent cellular cytotoxicity (ADCC).
[0196] The variable domains of natural light and heavy chains can have the same general structures, and each domain can comprise four framework regions, whose sequences can be somewhat conserved, connected by three CDRs. The four framework regions can largely adopt a (3-sheet conformation and the CDRs can form loops connecting, and in some aspects forming part of, the (3 -sheet structure. The CDRs in each chain can be held in close proximity by the framework regions and, with the CDRs from the other chain, can contribute to the formation of the antigen binding site.
[0197] An antibody can include an antibody of any type, which can be assigned to different classes of immunoglobins, e.g., IgA, IgD, IgE, IgG, and IgM. Several different classes can be further divided into isotypes, e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2.
Exemplary heavy chain sequences of reference antibodies can be used to identify residue variants and mutants.
[0198] An exemplary heavy chain sequence for human IgG1 heavy chain is that of the human IgG1 antibody, and can comprise:
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 898).
[0199] An exemplary heavy chain reference sequence for human IgG2 heavy chain can comprise:
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF
RVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 899).
[0200] An exemplary heavy chain reference sequence for human IgG4 heavy chain can comprise:
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW
QEG NVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 900).
[0201] The heavy-chain constant regions (Fc) that corresponds to the different classes of immunoglobulins can be a, 6, , y, and p.. The light chains can be one of either kappa or lc and lambda or k, based on the amino acid sequences of the constant domains. The Fc region can contain an Fc domain. An Fc receptor can bind an Fc domain. An Fc domain can comprise amino acid residues 216 to 447 of an IgGl, which are part of SEQ ID NO: 898. An Fc domain can comprise amino acid residues 216 to 442 of an IgG2, which are part of SEQ ID
NO: 899. An Fc domain can comprise amino acid residues 216 to 444 of an IgG4, which are part of SEQ ID NO:
900. Antibody constructs can also include any fragment or recombinant forms thereof (e.g., scFVs and domain antibodies). Antibody constructs can also include any fragment or recombinant forms thereof (e.g., scFVs and domain antibodies) of non-antibody scaffolds, including but not limited to anti-calins, affibodies, affilins, atrimers, avimers, bicyclic peptides, centyrins, Cys-knots, Darpins, fibronections, Kunitz domains, 0-bodies, or peptibodies.
[0202] An antibody construct can comprise an antigen binding domain of an antibody. An antigen binding domain of an antibody can comprise one or more light chain CDRs (LCDRs) and one or more heavy chain CDRs (HCDRs), or one or more LCDRs or one or more HCDRs. For example, an antibody binding domain of an antibody construct can comprise one or more of the following: a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), or a light chain complementary determining region 3 (LCDR3). For another example, an antibody binding domain can comprise one or more of the following: a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2), or a heavy chain complementary determining region 3 (HCDR3). In some embodiments, an antigen binding domain comprises LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3. Unless stated otherwise, the CDRs described herein can be defined according to the IMGT (the international ImMunoGeneTics information system).
[0203] An antigen binding domain can comprise only the heavy chain of an antibody. An antigen binding domain can comprise only the variable domain of the heavy chain of an antibody.
Alternatively, an antigen binding domain can comprise only the light chain of an antibody. An antigen binding domain can comprise only the variable light chain of an antibody.
[0204] An antibody construct can comprise an antibody fragment. An antibody fragment can include (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; and (iii) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody. Although the two domains of the Fv fragment, VL and VH, can be coded for by separate genes, they can be linked by a synthetic linker to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules. F(ab')2 and Fab' moieties can be produced recombinantly.
[0205] An Fv can be the minimum antibody fragment which contains a complete antigen-recognition and antigen-binding site. This region can consist of a dimer of one heavy chain and one light chain variable domain in tight, non-covalent association. In this configuration the three hypervariable regions of each variable domain can interact to define an antigen-binding site on the surface of the VH-VL dimer. A single variable domain (or half of an Fv comprising only CDRs specific for an antigen) can recognize and bind antigen, although at a lower affinity than the entire binding site.
[0206] An antibody used herein can be chimeric or "humanized." Chimeric and humanized forms of non-human (e.g., murine) antibodies can be chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other target-binding subdomains of antibodies), which can contain minimal sequences derived from non-human immunoglobulin. In general, the humanized antibody can comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR
regions correspond to those of a non-human immunoglobulin and all or substantially all of the frame work regions (FR) are those of a human immunoglobulin sequence. The humanized antibody can also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin consensus sequence.
[0207] An antibody described herein can be a human antibody. As used herein, "human antibodies" can include antibodies having, for example, the amino acid sequence of a human immunoglobulin and include antibodies isolated from human immunoglobulin libraries or from animals transgenic for one or more human immunoglobulins that do not express endogenous immunoglobulins. Human antibodies can be produced using transgenic mice which are incapable of expressing functional endogenous immunoglobulins, but which can express human immunoglobulin genes. Completely human antibodies that recognize a selected epitope can be generated using guided selection. In this approach, a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope
[0208] An antibody described herein can be a bispecific antibody or a dual variable domain antibody (DVD). Bispecific and DVD antibodies are monoclonal, often human or humanized, antibodies that have binding specificities for at least two different antigens.
[0209] An antibody described herein can be a derivatized antibody. For example, derivatized antibodies can be modified by glycosylation, deglycosylation, defucosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, or linkage to a cellular ligand or other protein.
[0210] An antibody described herein can have a sequence that has been modified to alter at least one constant region-mediated biological effector function relative to the corresponding wild type sequence. For example, in some embodiments, the antibody can be modified to reduce at least one constant region-mediated biological effector function relative to an unmodified antibody, e.g., reduced binding or increased binding to the Fc receptor (FcR). FcR binding can be reduced or increased by, for example, mutating the immunoglobulin constant region segment of the antibody at particular regions necessary for FcR interactions.
[0211] An antibody described herein can be modified to acquire or improve at least one constant region-mediated biological effector function relative to an unmodified antibody, e.g., to enhance FcyR interactions. For example, an antibody with a constant region that binds FcyRIIA, FcyRIIB
and/or FcyRIIIA with greater affinity than the corresponding wild type constant region can be produced according to the methods described herein.
[0212] An antibody described herein can bind to tumor cells, such as an antibody against a cell surface receptor or a tumor antigen.
[0213] An antibody construct can comprise a first binding domain. An antibody construct can comprise a first binding domain that specifically binds an antigen. An antibody construct can comprise a first binding domain that specifically binds a tumor antigen. A
first binding domain can specifically bind a tumor antigen, wherein the tumor antigen is selected from the group consisting CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV E7, Her-2/neu, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE
Al, MAGE A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof. An antibody construct can comprise a first binding domain that specifically binds a tumor antigen on a tumor cell, a tumor fragment, an immune cell or an antigen presenting cell.
[0214] An antibody construct can comprise a first binding domain that specifically binds a tumor antigen. The construct can comprise a first binding domain comprising one or more CDRs, typically a set of six CDRs. A first binding domain can comprise at least 80%
sequence identity to any sequence in TABLE 1. An antibody construct can comprise a first binding domain that binds a tumor antigen, wherein the first binding domain comprises at least 80%
sequence identity to: a) HCDR1 comprising an amino acid sequence of SEQ ID NO: 13, HCDR2 comprising an amino acid sequence of SEQ ID NO: 14, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 15, LCDR1 comprising an amino acid sequence of SEQ ID NO: 18, LCDR2 comprising an amino acid sequence of SEQ ID NO: 19, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 20; b) HCDR1 comprising an amino acid sequence of SEQ ID NO: 26, comprising an amino acid sequence of SEQ ID NO: 27, HCDR3 comprising an amino acid sequence of SEQ ID NO: 28, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 31, LCDR2 comprising an amino acid sequence of SEQ ID NO: 32, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 33; c) HCDR1 comprising an amino acid sequence of SEQ
ID NO: 39, HCDR2 comprising an amino acid sequence of SEQ ID NO: 40, HCDR3 comprising an amino acid sequence of SEQ ID NO: 41, LCDR1 comprising an amino acid sequence of SEQ
ID NO: 44, LCDR2 comprising an amino acid sequence of SEQ ID NO: 45, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 46; d) HCDR1 comprising an amino acid sequence of SEQ ID NO: 52, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 53, HCDR3 comprising an amino acid sequence of SEQ ID NO: 54, LCDR1 comprising an amino acid sequence of SEQ ID NO: 57, LCDR2 comprising an amino acid sequence of SEQ
ID NO:
58, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 59; e) HCDR1 comprising an amino acid sequence of SEQ ID NO: 65, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 66, HCDR3 comprising an amino acid sequence of SEQ ID NO: 67, LCDR1 comprising an amino acid sequence of SEQ ID NO: 70, LCDR2 comprising an amino acid sequence of SEQ
ID NO: 71, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 72; f) comprising an amino acid sequence of SEQ ID NO: 78, HCDR2 comprising an amino acid sequence of SEQ ID NO: 79, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 80, LCDR1 comprising an amino acid sequence of SEQ ID NO: 83, LCDR2 comprising an amino acid sequence of SEQ ID NO: 84, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 85; g) HCDR1 comprising an amino acid sequence of SEQ ID NO: 91, HCDR2 comprising an amino acid sequence of SEQ ID NO: 92, HCDR3 comprising an amino acid sequence of SEQ

ID NO: 93, LCDR1 comprising an amino acid sequence of SEQ ID NO: 96, LCDR2 comprising an amino acid sequence of SEQ ID NO: 97, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 98; h) HCDR1 comprising an amino acid sequence of SEQ ID NO: 104, comprising an amino acid sequence of SEQ ID NO: 105, HCDR3 comprising an amino acid sequence of SEQ ID NO: 106, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 109, LCDR2 comprising an amino acid sequence of SEQ ID NO: 110, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 111; i) HCDR1 comprising an amino acid sequence of SEQ
ID NO: 117, HCDR2 comprising an amino acid sequence of SEQ ID NO: 118, HCDR3 comprising an amino acid sequence of SEQ ID NO: 119, LCDR1 comprising an amino acid sequence of SEQ ID NO: 122, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 123, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 124; j) HCDR1 comprising an amino acid sequence of SEQ ID NO: 130, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 131, HCDR3 comprising an amino acid sequence of SEQ ID NO: 132, LCDR1 comprising an amino acid sequence of SEQ ID NO: 135, LCDR2 comprising an amino acid sequence of SEQ ID NO: 136, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
137; k) HCDR1 comprising an amino acid sequence of SEQ ID NO: 143, HCDR2 comprising an amino acid sequence of SEQ ID NO: 144, HCDR3 comprising an amino acid sequence of SEQ
ID NO: 145, LCDR1 comprising an amino acid sequence of SEQ ID NO: 148, LCDR2 comprising an amino acid sequence of SEQ ID NO: 149, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 150;1) HCDR1 comprising an amino acid sequence of SEQ
ID NO:
156, HCDR2 comprising an amino acid sequence of SEQ ID NO: 157, HCDR3 comprising an amino acid sequence of SEQ ID NO: 158, LCDR1 comprising an amino acid sequence of SEQID
NO: 161, LCDR2 comprising an amino acid sequence of SEQ ID NO: 162, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 163; m) HCDR1 comprising an amino acid sequence of SEQ ID NO: 169, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 170, HCDR3 comprising an amino acid sequence of SEQ ID NO: 171, LCDR1 comprising an amino acid sequence of SEQ ID NO: 174, LCDR2 comprising an amino acid sequence of SEQ ID NO:
175, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 176; n) HCDR1 comprising an amino acid sequence of SEQ ID NO: 182, HCDR2 comprising an amino acid sequence of SEQ ID NO: 183, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 184, LCDR1 comprising an amino acid sequence of SEQ ID NO: 187, LCDR2 comprising an amino acid sequence of SEQ ID NO: 188, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 189; o) HCDR1 comprising an amino acid sequence of SEQ ID NO: 195, HCDR2 comprising an amino acid sequence of SEQ ID NO: 196, HCDR3 comprising an amino acid sequence of SEQ ID NO: 197, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 200, LCDR2 comprising an amino acid sequence of SEQ ID NO: 201, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 202; p) HCDR1 comprising an amino acid sequence of SEQ ID NO: 208, HCDR2 comprising an amino acid sequence of SEQ ID NO: 209, comprising an amino acid sequence of SEQ ID NO: 210, LCDR1 comprising an amino acid sequence of SEQ ID NO: 213, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 214, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 215; q) HCDR1 comprising an amino acid sequence of SEQ ID NO: 805, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 806, HCDR3 comprising an amino acid sequence of SEQ ID NO: 807, LCDR1 comprising an amino acid sequence of SEQ ID NO: 808, LCDR2 comprising an amino acid sequence of SEQ ID NO: 809, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
810; r) HCDR1 comprising an amino acid sequence of SEQ ID NO: 823, HCDR2 comprising an amino acid sequence of SEQ ID NO: 824, HCDR3 comprising an amino acid sequence of SEQ
ID NO: 825, LCDR1 comprising an amino acid sequence of SEQ ID NO: 826, LCDR2 comprising an amino acid sequence of SEQ ID NO: 827, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 828; s) HCDR1 comprising an amino acid sequence of SEQ
ID NO:
221, HCDR2 comprising an amino acid sequence of SEQ ID NO: 222, HCDR3 comprising an amino acid sequence of SEQ ID NO: 223, LCDR1 comprising an amino acid sequence of SEQ
ID NO: 226, LCDR2 comprising an amino acid sequence of SEQ ID NO: 227, and comprising an amino acid sequence of SEQ ID NO: 228; t) HCDR1 comprising an amino acid sequence of SEQ ID NO: 260, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 261, HCDR3 comprising an amino acid sequence of SEQ ID NO: 262, LCDR1 comprising an amino acid sequence of SEQ ID NO: 265, LCDR2 comprising an amino acid sequence of SEQ ID NO:
266, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 267; u) HCDR1 comprising an amino acid sequence of SEQ ID NO: 273, HCDR2 comprising an amino acid sequence of SEQ ID NO: 274, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 275, LCDR1 comprising an amino acid sequence of SEQ ID NO: 278, LCDR2 comprising an amino acid sequence of SEQ ID NO: 279, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 280; v) HCDR1 comprising an amino acid sequence of SEQ ID NO: 286, HCDR2 comprising an amino acid sequence of SEQ ID NO: 287, HCDR3 comprising an amino acid sequence of SEQ ID NO: 288, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 291, LCDR2 comprising an amino acid sequence of SEQ ID NO: 292, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 293; w) HCDR1 comprising an amino acid sequence of SEQ ID NO: 299, HCDR2 comprising an amino acid sequence of SEQ ID NO: 300, comprising an amino acid sequence of SEQ ID NO: 301, LCDR1 comprising an amino acid sequence of SEQ ID NO: 304, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 305, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 306; x) HCDR1 comprising an amino acid sequence of SEQ ID NO: 312, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 313, HCDR3 comprising an amino acid sequence of SEQ ID NO: 314, LCDR1 comprising an amino acid sequence of SEQ ID NO: 317, LCDR2 comprising an amino acid sequence of SEQ ID NO: 318, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
319; y) HCDR1 comprising an amino acid sequence of SEQ ID NO: 325, HCDR2 comprising an amino acid sequence of SEQ ID NO: 326, HCDR3 comprising an amino acid sequence of SEQ
ID NO: 327, LCDR1 comprising an amino acid sequence of SEQ ID NO: 330, LCDR2 comprising an amino acid sequence of SEQ ID NO: 331, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 332; z) HCDR1 comprising an amino acid sequence of SEQ
ID NO:
338, HCDR2 comprising an amino acid sequence of SEQ ID NO: 339, HCDR3 comprising an amino acid sequence of SEQ ID NO: 340, LCDR1 comprising an amino acid sequence of SEQ
ID NO: 343, LCDR2 comprising an amino acid sequence of SEQ ID NO: 344, and comprising an amino acid sequence of SEQ ID NO: 345; aa) HCDR1 comprising an amino acid sequence of SEQ ID NO: 351, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 352, HCDR3 comprising an amino acid sequence of SEQ ID NO: 353, LCDR1 comprising an amino acid sequence of SEQ ID NO: 356, LCDR2 comprising an amino acid sequence of SEQ ID NO:
357, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 358; bb) HCDR1 comprising an amino acid sequence of SEQ ID NO: 364, HCDR2 comprising an amino acid sequence of SEQ ID NO: 365, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 366, LCDR1 comprising an amino acid sequence of SEQ ID NO: 369, LCDR2 comprising an amino acid sequence of SEQ ID NO: 370, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 371; cc) HCDR1 comprising an amino acid sequence of SEQ ID NO: 377, HCDR2 comprising an amino acid sequence of SEQ ID NO: 378, HCDR3 comprising an amino acid sequence of SEQ ID NO: 379, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 382, LCDR2 comprising an amino acid sequence of SEQ ID NO: 383, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 384; dd) HCDR1 comprising an amino acid sequence of SEQ ID NO: 390, HCDR2 comprising an amino acid sequence of SEQ ID NO: 391, comprising an amino acid sequence of SEQ ID NO: 392, LCDR1 comprising an amino acid sequence of SEQ ID NO: 395, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 396, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 397; ee) HCDR1 comprising an amino acid sequence of SEQ ID NO: 403, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 404, HCDR3 comprising an amino acid sequence of SEQ ID NO: 405, LCDR1 comprising an amino acid sequence of SEQ ID NO: 408, LCDR2 comprising an amino acid sequence of SEQ ID NO: 409, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:

410; ff) HCDR1 comprising an amino acid sequence of SEQ ID NO: 416, HCDR2 comprising an amino acid sequence of SEQ ID NO: 417, HCDR3 comprising an amino acid sequence of SEQ
ID NO: 418, LCDR1 comprising an amino acid sequence of SEQ ID NO: 421, LCDR2 comprising an amino acid sequence of SEQ ID NO: 422, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 423; gg) HCDR1 comprising an amino acid sequence of SEQ
ID NO:
429, HCDR2 comprising an amino acid sequence of SEQ ID NO: 430, HCDR3 comprising an amino acid sequence of SEQ ID NO: 431, LCDR1 comprising an amino acid sequence of SEQ
ID NO: 434, LCDR2 comprising an amino acid sequence of SEQ ID NO: 435, and comprising an amino acid sequence of SEQ ID NO: 436; hh) HCDR1 comprising an amino acid sequence of SEQ ID NO: 442, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 443, HCDR3 comprising an amino acid sequence of SEQ ID NO: 444, LCDR1 comprising an amino acid sequence of SEQ ID NO: 447, LCDR2 comprising an amino acid sequence of SEQ ID NO:
448, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 449; ii) HCDR1 comprising an amino acid sequence of SEQ ID NO: 455, HCDR2 comprising an amino acid sequence of SEQ ID NO: 456, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 457, LCDR1 comprising an amino acid sequence of SEQ ID NO: 460, LCDR2 comprising an amino acid sequence of SEQ ID NO: 461, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 462; jj) HCDR1 comprising an amino acid sequence of SEQ ID NO: 468, HCDR2 comprising an amino acid sequence of SEQ ID NO: 469, HCDR3 comprising an amino acid sequence of SEQ ID NO: 470, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 473, LCDR2 comprising an amino acid sequence of SEQ ID NO: 474, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 475; kk) HCDR1 comprising an amino acid sequence of SEQ ID NO: 481, HCDR2 comprising an amino acid sequence of SEQ ID NO: 482, comprising an amino acid sequence of SEQ ID NO: 483, LCDR1 comprising an amino acid sequence of SEQ ID NO: 486, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 487, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 488; 11) HCDR1 comprising an amino acid sequence of SEQ ID NO: 494, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 495, HCDR3 comprising an amino acid sequence of SEQ ID NO: 496, LCDR1 comprising an amino acid sequence of SEQ ID NO: 499, LCDR2 comprising an amino acid sequence of SEQ ID NO: 500, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
501; mm) HCDR1 comprising an amino acid sequence of SEQ ID NO: 673, HCDR2 comprising an amino acid sequence of SEQ ID NO: 674, HCDR3 comprising an amino acid sequence of SEQ ID NO: 675, LCDR1 comprising an amino acid sequence of SEQ ID NO: 676, comprising an amino acid sequence of SEQ ID NO: 677, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 678; nn) HCDR1 comprising an amino acid sequence of SEQ
ID NO:

850, HCDR2 comprising an amino acid sequence of SEQ ID NO: 851, HCDR3 comprising an amino acid sequence of SEQ ID NO: 852, LCDR1 comprising an amino acid sequence of SEQ
ID NO: 853, LCDR2 comprising an amino acid sequence of SEQ ID NO: 854, and comprising an amino acid sequence of SEQ ID NO: 855; oo) HCDR1 comprising an amino acid sequence of SEQ ID NO: 856, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 857, HCDR3 comprising an amino acid sequence of SEQ ID NO: 858, LCDR1 comprising an amino acid sequence of SEQ ID NO: 859, LCDR2 comprising an amino acid sequence of SEQ ID NO:
860, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 861; pp) HCDR1 comprising an amino acid sequence of SEQ ID NO: 862, HCDR2 comprising an amino acid sequence of SEQ ID NO: 863, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 864, LCDR1 comprising an amino acid sequence of SEQ ID NO: 865, LCDR2 comprising an amino acid sequence of SEQ ID NO: 866, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 867; qq) HCDR1 comprising an amino acid sequence of SEQ ID NO: 868, HCDR2 comprising an amino acid sequence of SEQ ID NO: 869, HCDR3 comprising an amino acid sequence of SEQ ID NO: 870, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 871, LCDR2 comprising an amino acid sequence of SEQ ID NO: 872, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 873; rr) HCDR1 comprising an amino acid sequence of SEQ ID NO: 874, HCDR2 comprising an amino acid sequence of SEQ ID NO: 875, comprising an amino acid sequence of SEQ ID NO: 876, LCDR1 comprising an amino acid sequence of SEQ ID NO: 877, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 878, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 879; or ss) HCDR1 comprising an amino acid sequence of SEQ ID NO: 880, HCDR2 comprising an amino acid sequence of SEQ ID NO: 881, HCDR3 comprising an amino acid sequence of SEQ ID NO: 882, comprising an amino acid sequence of SEQ ID NO: 883, LCDR2 comprising an amino acid sequence of SEQ ID NO: 884, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
885.
[0215] An antibody construct can comprise a first binding domain that specifically binds a tumor antigen. An antibody construct can comprise a first binding domain comprising one or more variable domains. An antibody construct can comprise a first binding domain comprising a light chain variable domain (VL domain). A first binding domain can have at least 80% or 100%
sequence identity to any VL sequence in TABLE 2. An antibody construct can comprise a first binding domain comprising a heavy chain variable domain (VH domain). A first binding domain can comprise at least 80% or 100% sequence identity to any VH sequence in TABLE 2. A first binding domain can comprise at least 80% sequence identity to any sequence in TABLE 2. A

first binding domain can have a pair of VH and VL regions, having sequence selected from the pairs in TABLE 2.
[0216] An antibody construct can comprise a first binding domain that specifically binds a tumor antigen, wherein the first binding domain comprises: a) a VH sequence having at least 80% or 100% sequence identity to an amino acid sequence of SEQ ID NO: 12, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 17; b) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
25, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 30; c) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
38, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ
ID NO: 43; d) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 51, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 56; e) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 64, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 69; f) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 77, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 82; g) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 90, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 95; h) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
103, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 108; i) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
116, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ
ID NO: 121; j) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 129, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 134; k) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 142, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 147; 1) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 155, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 160; m) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
168, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 173; n) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
181, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ
ID NO: 186; o) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 194, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 199; p) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 207, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 212; q) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 811, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 812; r) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
829, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 830; s) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
220, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ
ID NO: 225; t) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 259, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 264; u) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 272, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 277; v) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 285, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 290; w) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
298, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 303; x) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
311, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ
ID NO: 316; y) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 324, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 328; z) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 337, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 342; aa) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 350, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 355; bb) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
363, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 368;
cc) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID
NO: 376, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 381; dd) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 389, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 394; ee) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 402, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 407; ff) a VH
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 415, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
420; gg) a VH
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 428, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID
NO: 433; hh) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 441, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 446; ii) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 454, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 459; jj) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 467, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 472; kk) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
480, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 485;
11) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID
NO: 493, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 498; mm) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 679, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 680; nn) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 886, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 887; oo) a VH
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 888, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
889; pp) a VH
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 890, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID
NO: 891; qq) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 892, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 893; rr) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 894, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO:895; ss) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 896, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 897.
[0217] An antibody construct can comprise a first binding domain and an Fc domain, wherein the first binding domain and the Fc domain comprise an antibody. A first binding domain can specifically bind a tumor antigen. An antibody construct can comprise an antibody light chain wherein the antibody construct specifically binds to an antigen. An antibody construct can comprise a light chain comprising at least 80% or 100% sequence identity to a light chain sequence in TABLE 3, wherein the antibody construct specifically binds to an antigen. An antibody construct can comprise an antibody heavy chain, wherein the antibody construct specifically binds to an antigen. An antibody construct can comprise a heavy chain comprising at least 80% or 100% sequence identity to a heavy chain sequence in TABLE 3, wherein the antibody construct specifically binds to an antigen. An antibody construct can comprise at least 80% sequence identity to any sequence in TABLE 3, wherein the antibody construct specifically binds to an antigen. An antibody construct can have a pair of heavy and light chains having sequences selected from the pairs of sequences in TABLE 3, wherein the antibody construct specifically binds to an antigen.
[0218] An antibody construct can comprise an anti-tumor antibody, wherein the antibody comprises: a) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 11, and a light chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 16; b) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 24, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
29; c) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
37, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 42; d) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 50, and a light chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 55; e) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 63, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
68; f) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
76, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 81; g) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 89, and a light chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 94; h) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 102, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 107;
i) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 115, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 120; j) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 128, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 133; k) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 141, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 146;1) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 154, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 159; m) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 167, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 172;
n) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 180, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 185; o) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 193, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 198; p) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 206, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 211; q) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 813, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 814; r) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 831, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 832;
s) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 219, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 224; t) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 258, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 263; u) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 271, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 276; v) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 284, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 289; w) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 297, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 302;
x) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 310, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 315; y) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 323, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 328; z) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 336, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 341; aa) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 349, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 354; bb) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 362, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 367;
cc) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 375, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 380; dd) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 388, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 393; ee) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 401, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 406; ff) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 414, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 419; gg) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 427, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 432;
hh) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 440, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 445; ii) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 453, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 458; jj) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 466, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 471; kk) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 479, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 484; 11) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 492, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 497;
or mm) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 681, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 682.
[0219] An antibody construct can comprise a second binding domain that specifically binds to an antigen. An antibody construct can comprise a second binding domain that specifically binds to an antigen on an antigen presenting cell. An antigen presenting cell can be a dendritic cell or a macrophage. A second binding domain can specifically bind to an antigen on an immune cell such as an antigen presenting cell, wherein the molecule comprises at least 80% sequence identity to a group consisting of CD40, CD47, TNFR2, DEC-205, PD-L1, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, CD38, TREM2, CSF1R, or CD32B.
[0220] An antibody construct can further comprise an Fc domain. An antibody construct can comprise, for example, a first binding domain, a second binding domain, and an Fc domain, wherein the first binding domain is attached to the Fc domain. An antibody construct can comprise a first binding domain, a second binding domain, and an Fc domain, wherein the second binding domain is attached to the Fc domain. A first binding domain can be attached to an Fc domain as a fusion protein. A second binding domain can be attached to an Fc domain as a fusion protein. A first binding domain can be attached to an Fc domain via a linker. A second binding domain can be attached to an Fc domain via a linker.
[0221] An antibody construct can comprise a second binding domain comprising one or more CDRs. A second binding domain can comprise at least 80% sequence identity to any sequence in TABLE 5. A second binding domain can comprise a set of CDRs having the sequences set forth in any sete of sequence in TABLE 5.
[0222] An antibody construct can comprise a second binding domain that specifically binds to CD40. An antibody construct can comprise a second binding domain that is a CD40 agonist. An antibody construct can comprise a second binding domain that binds to CD40, wherein the second binding domain comprises at least 80% sequence identity to: a) HCDR1 comprising an amino acid sequence of SEQ ID NO: 3, HCDR2 comprising an amino acid sequence of SEQ ID
NO: 4, HCDR3 comprising an amino acid sequence of SEQ ID NO: 5, LCDR1 comprising an amino acid sequence of SEQ ID NO: 8, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 9, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 10; b) HCDR1 comprising an amino acid sequence of SEQ ID NO: 582, HCDR2 comprising an amino acid sequence of SEQ ID NO: 583, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 584, LCDR1 comprising an amino acid sequence of SEQ ID NO: 587, LCDR2 comprising an amino acid sequence of SEQ ID NO: 588, and LCDR3 comprising an amino acid sequence of SEQ ID

NO: 589; c) HCDR1 comprising an amino acid sequence of SEQ ID NO: 592, HCDR2 comprising an amino acid sequence of SEQ ID NO: 593, HCDR3 comprising an amino acid sequence of SEQ ID NO: 594, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 597, LCDR2 comprising an amino acid sequence of SEQ ID NO: 598, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 599; d) HCDR1 comprising an amino acid sequence of SEQ ID NO: 602, HCDR2 comprising an amino acid sequence of SEQ ID NO: 603, comprising an amino acid sequence of SEQ ID NO: 604, LCDR1 comprising an amino acid sequence of SEQ ID NO: 607, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 608, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 609; e) HCDR1 comprising an amino acid sequence of SEQ ID NO: 612, HCDR2 comprising an amino acid sequence of SEQ
ID NO: 613, HCDR3 comprising an amino acid sequence of SEQ ID NO: 614, LCDR1 comprising an amino acid sequence of SEQ ID NO: 617, LCDR2 comprising an amino acid sequence of SEQ ID NO: 618, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
619; f) HCDR1 comprising an amino acid sequence of SEQ ID NO: 622, HCDR2 comprising an amino acid sequence of SEQ ID NO: 623, HCDR3 comprising an amino acid sequence of SEQ
ID NO: 624, LCDR1 comprising an amino acid sequence of SEQ ID NO: 627, LCDR2 comprising an amino acid sequence of SEQ ID NO: 628, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 629; or g) HCDR1 comprising an amino acid sequence of SEQ ID NO:
632, HCDR2 comprising an amino acid sequence of SEQ ID NO: 633, HCDR3 comprising an amino acid sequence of SEQ ID NO: 634, LCDR1 comprising an amino acid sequence of SEQ
ID NO: 637, LCDR2 comprising an amino acid sequence of SEQ ID NO: 638, and comprising an amino acid sequence of SEQ ID NO: 639.
[0223] An antibody construct can comprise a second binding domain that specifically binds DC-SIGN. An antibody construct can comprise a second binding domain that binds DC-SIGN, wherein the second binding domain comprises at least 80% sequence identity to:
a) HCDR1 comprising an amino acid sequence of SEQ ID NO: 640, HCDR2 comprising an amino acid sequence of SEQ ID NO: 641, HCDR3 comprising an amino acid sequence of SEQ ID
NO: 642, LCDR1 comprising an amino acid sequence of SEQ ID NO: 643, LCDR2 comprising an amino acid sequence of SEQ ID NO: 644, and LCDR3 comprising an amino acid sequence of SEQ ID
NO: 645; b) HCDR1 comprising an amino acid sequence of SEQ ID NO: 646, HCDR2 comprising an amino acid sequence of SEQ ID NO: 647, HCDR3 comprising an amino acid sequence of SEQ ID NO: 648, LCDR1 comprising an amino acid sequence of SEQ ID
NO: 649, LCDR2 comprising an amino acid sequence of SEQ ID NO: 650, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 651; or c) HCDR1 comprising an amino acid sequence of SEQ ID NO: 652, HCDR2 comprising an amino acid sequence of SEQ ID NO: 653, comprising an amino acid sequence of SEQ ID NO: 654, LCDR1 comprising an amino acid sequence of SEQ ID NO: 655, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 656, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 657.
[0224] An antibody construct can comprise a second binding domain that specifically binds DEC-205. An antibody construct comprising a second binding domain that binds DEC-205 can comprise at least 80% sequence identity to: a) HCDR1 comprising an amino acid sequence of SEQ ID NO: 234, HCDR2 comprising an amino acid sequence of SEQ ID NO: 235, comprising an amino acid sequence of SEQ ID NO: 236, LCDR1 comprising an amino acid sequence of SEQ ID NO: 239, LCDR2 comprising an amino acid sequence of SEQ ID
NO: 240, and LCDR3 comprising an amino acid sequence of SEQ ID NO: 241; orb) HCDR1 comprising an amino acid sequence of SEQ ID NO: 247, HCDR2 comprising an amino acid sequence of SEQ ID NO: 248, HCDR3 comprising an amino acid sequence of SEQ ID NO: 249, comprising an amino acid sequence of SEQ ID NO: 252, LCDR2 comprising an amino acid sequence of SEQ ID NO: 253, and LCDR3 comprising an amino acid sequence of SEQ
ID NO:
254.
[0225] An antibody construct can comprise a second binding domain comprising one or more variable domains. An antibody construct can comprise a second binding domain comprising a light chain variable domain (VL domain). A second binding domain can comprise at least 80%
sequence identity to any VL sequence in TABLE 6. An antibody construct can comprise a second binding domain comprising a heavy chain variable domain. A second binding domain can comprise at least 80% sequence identity to any VH sequence in TABLE 6. A
second binding domain can comprise at least 80% sequence identity to any sequence in TABLE 6.
A second binding domain can comprise at a pair of VH and VL domains having a pair of sequences in TABLE 6.
[0226] An antibody construct can comprise a second binding domain that specifically binds CD40. An antibody construct can comprise a second binding domain that is a CD40 agonist. An antibody construct can comprise a second binding domain that binds CD40, wherein the second binding domain comprises: a) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 2, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 7; b) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 581, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 586; c) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 591, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 596; d) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
601, and a VL

sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 606;
e) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID
NO: 611, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 616; f) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 621, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 626; g) a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 631, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 636.
[0227] An antibody construct can comprise a second binding domain that specifically binds DEC-205. An antibody construct can comprise a second binding domain that binds DEC-205, wherein the second binding domain comprises: a) a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 233, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 238; or b) a VH
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 246, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
251.
[0228] An antibody construct can comprise a second binding domain that specifically binds to CD36 mannose scavenger receptor 1. An antibody construct can comprise a second binding domain that binds CD36 mannose scavenger receptor 1, wherein the second binding domain comprises a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 658, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 659.
[0229] An antibody construct can comprise a second binding domain that specifically binds to CLEC9A. An antibody construct can comprise a second binding domain that binds CLEC9A, wherein the second binding domain comprises a VH sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 660, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 661.
[0230] An antibody construct can comprise a second binding domain that specifically binds to PD-Li. An antibody construct can comprise a second binding domain that binds PD-L1, wherein the second binding domain comprises a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 901, and a VL sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 902; or wherein the second binding domain comprises a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 890, and a VL sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 891; or wherein the second binding domain comprises a VH sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
892, and a VL
sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 893.
[0231] An antibody construct can comprise a second binding domain and an Fc domain, wherein the second binding domain and the Fc domain comprise an antibody. An antibody construct can comprise a heavy chain and a light chain that target an antigen expressed by an antigen presenting cell. An antibody construct can comprise an antibody light chain.
An antibody construct can comprise a light chain comprising at least 80% sequence identity to any light chain sequence in TABLE 7. An antibody construct can comprise an antibody heavy chain. An antibody construct can comprise a heavy chain comprising at least 80% sequence identity to any heavy chain sequence in TABLE 7. An antibody construct can comprise at least 80% sequence identity to any sequence in TABLE 7. An antibody construct can comprise a heavy and light chains having a pair of sequences in TABLE 7.
[0232] An antibody construct can comprise a heavy chain and a light chain that target an antigen expressed by an antigen presenting cell. An antibody construct can comprise a first binding domain and an Fc domain, wherein the first binding domain and the Fc domain comprise an antibody. An antibody construct may comprise an anti-CD40 antibody, the antibody construct comprising: a) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 1 and a light chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 6; b) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 577 or SEQ ID NO:
578, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
579; c) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 580, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 585; d) a heavy chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 590, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
595; e) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
600, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 605; f) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 610, and a light chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 615; g) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
620, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO:
625; or h) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 630, and a light chain sequence having at least 80%
sequence identity to an amino acid sequence of SEQ ID NO: 635.
[0233] An antibody construct can comprise a first binding domain and an Fc domain, wherein the first binding domain and the Fc domain comprise an antibody. An antibody construct may comprise an anti-DEC-205 antibody, the construct comprising: a) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 232, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 237;
or b) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 245, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 250.
[0234] An antibody construct can comprise a first binding domain and an Fc domain, wherein the first binding domain and the Fc domain comprise an antibody. A composition may comprise an anti-CLEC12A antibody, the construct comprising: a) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 662, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 665;
b) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 663, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 665; or c) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 664, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 665.
[0235] An antibody construct can comprise a first binding domain and an Fc domain, wherein the first binding domain and the Fc domain comprise an antibody. An antibody construct may comprise an anti-BDCA-2 antibody, the construct comprising: a) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 666, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 669;
b) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 667, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 670; or c) a heavy chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 668, and a light chain sequence having at least 80% sequence identity to an amino acid sequence of SEQ ID NO: 671.
Antibody-ScFv Fusion Protein Products
[0236] An antibody construct can comprise a first binding domain, a second binding domain, and an Fc domain, wherein the first binding domain and the second binding domain are attached to the Fc domain. The first binding domain and the second binding domain can be attached to the Fc domain as a fusion protein. The first binding domain can be attached to the Fc domain at an N-terminal end of the Fc domain, wherein the second binding domain can be attached to the Fc domain at a C-terminal end. The first binding domain can be attached to the Fc domain at an N-terminal end of the Fc domain, wherein the second binding domain can be attached to the Fc domain at a C-terminal end via a polypeptide linker ranging from 10 to 25 amino acids. In some embodiments, the polypeptide linker has the sequence [G4S]n where n = 2 to 5.
Alternatively, the first binding domain can be attached to the Fc domain at a C-terminal end of the Fc domain, wherein the second binding domain can be attached to the Fc domain at an N-terminal end. A
second binding domain and an Fc domain can comprise an antibody and a first binding domain can comprise a single chain variable fragment (scFv). A single chain variable fragment can comprise a heavy chain variable domain and a light chain variable domain of an antibody. The first binding domain of the fusion protein can be attached to the second binding domain at a heavy chain variable domain of the single chain variable fragment of the first binding domain (HL orientation). Alternatively, the first binding domain of the fusion protein can be attached to the second binding domain at a light chain variable domain of the single chain variable fragment of the first binding domain (LH orientation). In either orientation, the first binding domain and the second binding domain can be attached via a polypeptide linker varying in length from 15 to 25 amino acids. In some embodiments, the polypeptide linker has the sequence [G4S]n where n =3 to 5.
[0237] Alternatively, an antibody construct can comprise an antibody (having two antigen binding domains and an Fc domain) and the second binding domain can comprise a single chain variable fragment (scFv). The second binding domain of the fusion protein can be attached to the first binding domain at a heavy chain variable domain of the single chain variable fragment of the first binding domain (HL orientation). Alternatively, the second binding domain of the fusion protein can be attached to the first binding domain at a light chain variable domain of the single chain variable fragment of the first binding domain (LH orientation).
[0238] An antibody construct can comprise a first binding domain and a second binding domain, wherein the second binding domain can be attached to the first binding domain.
The antibody construct can comprise an antibody comprising a light chain and a heavy chain or pair of heavy and light chains. The first binding domain can comprise an Fab fragment of the light and heavy chains. The second binding domain can be attached to the light chain at a C-terminus or C-terminal end of the light chain as a fusion protein. The second binding domain can comprise a single chain variable fragment (scFv). In some embodiments, a first binding domain can be specific for any of the tumor antigens, e.g., CEA, HER2, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, or gpNMB, and an scFv can be a binding domain with a specificity selected from a group consisting of antigens on antigen presenting cells, such as CD40, DEC205, and PD-Li.
[0239] An antibody construct can comprise a first binding domain, a second binding domain, and an Fc domain, wherein the first binding domain and the second binding domain are attached to the Fc domain as a fusion protein. The second binding domain of the fusion protein can specifically target an antigen with at least 80% sequence identity to CD40.
The second binding domain of the fusion protein can be a CD40 agonist. The first binding domain of the fusion protein can target a tumor antigen. The construct can comprise a fusion protein comprising a heavy chain (HC) attached to a single chain variable fragment. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence in TABLE 4. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a heavy chain CD40 monoclonal antibody (mAb) with tumor ScFv in TABLE 4.
The construct can comprise a fusion protein comprising at least 80% sequence identity to any sequence of a heavy chain CD40 mAb with tumor ScFv in TABLE 4 and a light chain comprising at least 80% sequence identity to SEQ ID NO: 6. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a heavy chain tumor mAb with CD40 ScFv in TABLE 4. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a heavy chain tumor antigen mAb with CD40 ScFv in TABLE 4, and at least 80% sequence identity to a light chain mAb for the tumor antigen in TABLE 3.
[0240] An antibody construct can comprise a first binding domain and a second binding domain, wherein the second binding domain can be attached to the first binding domain.
An antibody construct can comprise a first binding domain, a second binding domain, and an Fc domain, wherein the second binding domain can be attached to the first binding domain.
The second binding domain can be attached at a C-terminal end of the first binding domain as a fusion protein. The first binding domain can comprise a Fab fragment comprising a light chain, wherein the second binding domain can be attached at a C-terminal end of the light chain as a fusion protein. The second binding domain of the fusion protein can comprise a single chain variable fragment (scFv). The second binding domain of the fusion protein can be attached to the first binding domain at a heavy chain variable domain of the single chain variable fragment of the first binding domain (HL orientation). Alternatively, the second binding domain of the fusion protein can be attached to the first binding domain at a light chain variable domain of the single chain variable fragment of the first binding domain (LH orientation). For example, a fusion protein comprising a light chain of an anti-CEA antibody attached to an anti-CD40 scFv in the LH
orientation can be illustrated by SEQ ID NO: 842. The fusion sequences comprising an scFv sequence are in the HL orientation unless indicated otherwise (e.g., sequence name recites "(LH)" indicating light heavy orientation).
[0241] The first binding domain of the fusion protein can target a tumor antigen. The second binding domain of the fusion protein can target an APC antigen. The second binding domain of the fusion protein can target CD40. The first binding domain can comprise a Fab fragment comprising a light chain, wherein the second binding domain is attached at a C-terminal end of the light chain as a fusion protein. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence in TABLE 9. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a light chain CD40 mAb with tumor ScFv in TABLE 9. The construct can comprise a fusion protein comprising at least 80% sequence identity to any sequence of a light chain CD40 mAb with tumor ScFv in TABLE
9 and a heavy chain comprising at least 80% sequence identity to SEQ ID NO: 1.
The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a light chain tumor mAb with CD40 ScFv in TABLE 9. The construct can comprise a fusion protein comprising at least 80% sequence identity to any sequence of a light chain tumor antigen mAb with CD40 ScFv in TABLE 9, and at least 80% sequence identity to a heavy chain mAb for the tumor antigen in TABLE 3.
[0242] An antibody construct can comprise a first binding domain, a second binding domain, and an Fc domain, wherein the first binding domain and the second binding domain are attached to the Fc domain as a fusion protein. The first binding domain of the fusion protein can specifically target an antigen with at least 80% sequence identity to DEC-205. The second binding domain of the fusion protein can target a tumor antigen. The construct can comprise a fusion protein comprising a heavy chain attached to a single chain variable fragment. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence in TABLE 8. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a heavy chain DEC-205 mAb with tumor ScFv in TABLE 8. The construct can comprise a fusion protein comprising at least 80% sequence identity to any sequence of a heavy chain DEC-205 mAb with tumor ScFv in TABLE 8 and a peptide comprising at least 80%
sequence identity to SEQ ID NO: 237. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a heavy chain tumor antigen mAb with CD40 ScFv in TABLE 8. The construct comprising the fusion protein can comprise at least 80%
sequence identity to any sequence of a heavy chain tumor antigen mAb with CD40 ScFv in TABLE 8, and at least 80% sequence identity to a heavy chain mAb for the tumor antigen in TABLE 3.
[0243] The second binding domain of the fusion protein can target DEC-205. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence in TABLE 10. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a light chain DEC-205 mAb with tumor ScFv in TABLE
10. The construct comprising a fusion protein can comprise at least 80% sequence identity to any sequence of a light chain DEC-205 mAb with tumor ScFv in TABLE 10 and at least 80%
sequence identity to SEQ ID NO: 237. The construct comprising the fusion protein can comprise at least 80% sequence identity to any sequence of a light chain tumor mAb with DEC-205 ScFv in TABLE 10. The construct comprising a fusion protein can comprise at least 80% sequence identity to any sequence of a light chain tumor antigen mAb with DEC-205 ScFv in TABLE 10, and at least 80% sequence identity to a heavy chain mAb for the tumor antigen in TABLE 3.
[0244] The second binding domain of the fusion protein can specifically bind to an antigen of an Antigen Presenting Cell (APC) or other immune cell. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD40. The second binding domain of the fusion protein can be a CD40 agonist. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80%
sequence identity to DEC-205. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to DC-SIGN. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD36 mannose scavenger receptor. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CLEC12A. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to BDCA-2.
The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to PD-Li. The second binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD40, CD47, TNFR2, DEC-205, PD-L1, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, CD38, TREM2, CSF1R, or CD32B. The first binding domain of the fusion protein can specifically bind to a tumor antigen. The first binding domain of the fusion protein can specificall bind to an antigen with at least 80% sequence identity to CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV
E7, Her-2/neu, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, MYCN, RhoC, TRP-2, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, CYP1B1, PLAV1, BORIS, ETV6-AML, NY-BR-1, RGS5, SART3, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, PD-L1, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof.
[0245] Alternatively, the second binding domain of the fusion protein can target a tumor antigen.
The second binding domain of the fusion protein can specifically bind to an antigen selected from CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6 E7, Her-2/neu, p53 nonmutant, NY-ES0-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, MAGE
A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, PD-L1, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof. The first binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD40.
The first binding domain of the fusion protein can be a CD40 agonist. The first binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to DEC-205. The first binding domain of the fusion protein can specifically bind to an antigen with at least 80%
sequence identity to CEA, HER2, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA or gpNMB. The first binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD40, CD47, TNFR2, DEC-205, PD-L1, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, CD38, TREM2, CSF1R, or CD32B.
[0246] An antibody construct can comprise a first binding domain, a second binding domain, and a third binding domain. An antibody construct can comprise a first binding domain, a second binding domain, a third binding domain, and an Fc domain. The first binding domain and the second binding domain can be attached to the Fc domain. The first and second binding domains are described herein throughout the specification. The first binding domain can be attached to the Fc domain at an N-terminal end of the Fc domain. The second binding domain can be attached at a C-terminal end of the Fc domain. The second binding domain can be attached at a C-terminal end of the Fc domain via a polypeptide linker having a length of 10 to 25 amino acid. In some embodiments, the polypeptide linker has the sequence [G45]n where n = 2 to 5.
The third binding domain can be attached to a C-terminal end of the first binding domain. The third binding domain can be attached at a C-terminal end of the Fc domain via a polypeptide linker having a length of 10 to 25 amino acid. In some embodiments, the polypeptide linker has the sequence [G45]n where n = 2 to 5. The third binding domain can be attached to a C-terminal end of a light chain of the first binding domain. One or more of the first binding domain, the second binding domain, the third binding domain, and the Fc domain can be attached as a fusion protein. The first binding domain can comprise a Fab fragment comprising a light chain, wherein the second binding domain is attached at a C-terminal end of the light chain as a fusion protein. The second binding domain of the fusion protein can comprise a single chain variable fragment (scFv). The second binding domain of the fusion protein can be attached to the Fc domain at a heavy chain variable domain of the single chain variable fragment of the second binding domain (HL
orientation). The second binding domain of the fusion protein can be attached to the Fc domain at a light chain variable domain of the single chain variable fragment of the second binding domain (LH orientation). The third binding domain of the fusion protein can comprise a single chain variable fragment (scFv). The antibody construct can comprise a fusion protein comprising the third binding domain attached to the first binding domain having at least 80%
sequence identity to any sequence in TABLE 9 or TABLE 10. The third binding domain of the fusion protein can be attached to the first binding domain at a heavy chain variable domain of the single chain variable fragment of the first binding domain (HL orientation). Alternatively, the third binding domain of the fusion protein can be attached to the first binding domain at a light chain variable domain of the single chain variable fragment of the first binding domain (LH
orientation). The third binding domain of the fusion protein can target an antigen of an immune cell, such as an antigen presenting cell (APC). The third binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD40. The third binding domain of the fusion protein can be a CD40 agonist. The third binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to DEC-205. The third binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD40, CD47, TNFR2, DEC-205, PD-L1, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, CD38, TREM2, CSF1R, or CD32B.
[0247] Alternatively, the third binding domain can target a tumor antigen. The third binding domain of the fusion protein can specifically bind to an antigen with at least 80% sequence identity to CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6, HPV
E7, Her-2/neu, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, MYCN, RhoC, TRP-2, mesothelin (MSLN), PSCA, MAGE Al, MAGE A3, CYP1B1, PLAV1, BORIS, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, PAGE4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof. In additional embodiments, the third binding domain of the fusion protein can specifically bind to an antigen selected from CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Leg, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, avf33, WT1, LMP2, HPV E6 E7, Her-2/neu, p53 nonmutant, NY-ES0-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin Bl, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE Al, MAGE
A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES 1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, PAGE4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAILl, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, Clorf186, Fos-related antigen 1, VEGFR1, endoglin, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof.
[0248] An antibody construct can comprise a first binding domain targeting CD40 and a second binding domain targeting DEC-205. Alternatively, an antibody construct can comprise a first binding domain targeting DEC-205 and a second binding domain targeting CD40.
An antibody construct can comprise a first binding domain, a second binding domain, and an Fc domain. The first binding domain and the second binding domain can be attached to the Fc domain. The first binding domain can be attached to the Fc domain at an N-terminal end of the Fc domain, wherein the second binding domain is attached to the Fc domain at a C-terminal end of the Fc domain.
Alternatively, the second binding domain can be attached to the Fc domain at an N-terminal end of the Fc domain, wherein the first binding domain is attached to the Fc domain at a C-terminal end of the Fc domain. An antibody construct can comprise a fusion protein comprising a first binding domain targeting CD40 and a second binding domain targeting DEC-205.
The fusion protein can comprise at least 80% sequence identity to any sequence in TABLE
11.
[0249] Additionally, antibody constucts expressing proteins having the sequences referenced in Tables 1-11 can have a dissociation constant (Kd) that is less than 10 nM for the antigen of the first binding domain. The antibody constructs expressing proteins having the sequences referenced in Tables 1-11 can have a dissociation constant (Kd) that is less than 10 nM for the antigen of the second binding domain. The antibody constructs expressing the sequences referenced in Tables 1-11 can have a dissociation constant (Kd) that is less than 10 nM for the antigen of the third binding domain. The antibody constructs can have a dissociation constant (Kd) for the antigen of the first binding domain that is less than 1 nM, less than 100 pM, less than pM, less than 1 pM, or less than 0.1 pM. The antibody constructs can have a dissociation constant (Kd) for the antigen of the second binding domain that is less than 1 nM, less than 100 pM, less than 10 pM, less than 1 pM, or less than 0.1 pM. The antibody constructs can have a dissociation constant (Kd) for the antigen of the third binding domain that is less than 1 nM, less than 100 pM, less than 10 pM, less than 1 pM, or less than 0.1 pM.
[0250] An anti-CD40 light chain can be expressed with an anti-CD40 heavy chain or fragment thereof, wherein the light and heavy chains specifically bind to CD40. The anti-CD40 light chain can also be expressed with an anti-CD40 heavy chain or fragment thereof to form an anti-CD40 antibody or fragment thereof, wherein the antibody or antibody fragment specifically binds to CD40. The anti-CD40 antibody or fragment thereof can be purified, and can be combined with a pharmaceutically acceptable carrier.
[0251] An anti-DEC-205 light chain can be expressed with any anti-DEC-205 heavy chain or fragment thereof, wherein the light and heavy chains specifically bind to DEC-205. The anti-DEC-205 light chain can also be expressed with an anti-DEC-205 heavy chain or fragment thereof to form an anti-DEC-205 antibody or fragment thereof, wherein the antibody or antibody fragment specifically binds to DEC-205. The anti-DEC-205 antibody or fragment thereof can be purified, and can be combined with a pharmaceutically acceptable carrier.
[0252] An anti-PD-Li light chain can be expressed with any anti-PD-Li heavy chain or fragment thereof, wherein the light and heavy chains specifically bind to PD-Li. The anti-PD-Li light chain can also be expressed with an anti-PD-Li heavy chain or fragment thereof to form an anti-PD-Li antibody or fragment thereof, wherein the antibody or antibody fragment specifically binds to PD-Li. The anti-PD-Li antibody or fragment thereof can be purified, and can be combined with a pharmaceutically acceptable carrier.
[0253] An anti-tumor antigen light chain can be expressed with any anti-tumor antigen heavy chain or fragment thereof, wherein the antibody or antibody fragment specifically binds to tumor antigen. The anti-tumor antigen light chain can also expressed with any anti-tumor antigen heavy chain or fragment thereof to form an anti-tumor antigen antibody or fragment thereof. The anti-tumor antibody or fragment thereof can be purified, and can be combined with a pharmaceutically acceptable carrier.
[0254] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be an IgG1 isotype. A heavy chain of an anti-CD40 antibody can be dacetuzumab.
[0255] An antibody construct can comprise an antibody light chain. A light chain can be a light chain of an anti-CD40 antibody which can bind a CD40 antigen. A light chain of an anti-CD40 antibody can be dacetuzumab.
[0256] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be an IgG4 isotype. A heavy chain of an anti-CD40 antibody can be bleselumab.
[0257] An antibody construct can comprise an antibody light chain. A light chain can be a light chain of an anti-CD40 antibody which can bind a CD40 antigen. A light chain of an anti-CD40 antibody can be bleselumab.
[0258] An antibody constructcan comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be an IgG1 isotype. A heavy chain of an anti-CD40 antibody can be lucatumumab.
[0259] An antibody construct can comprise an antibody light chain. A light chain can be a light chain of an anti-CD40 antibody which can bind a CD40 antigen. A light chain of an anti-CD40 antibody can be lucatumumab.
[0260] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be an IgG1 isotype. A heavy chain of an anti-CD40 antibody can be ADC-1013.
[0261] An antibody construct can comprise an antibody light chain. A light chain can be a light chain of an anti-CD40 antibody which can bind a CD40 antigen. A light chain of an anti-CD40 antibody can be ADC-1013.
[0262] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be the humanized rabbit antibody APX005.
[0263] An antibody construct can comprise an antibody light chain. A light chain can be a light chain of an anti-CD40 antibody which can bind a CD40 antigen. A light chain of an anti-CD40 antibody can be the humanized rabbit antibody APX005.
[0264] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be Chi Lob 7/4.
[0265] An antibody construct can comprise an antibody light chain. A light chain can be a light chain of an anti-CD40 antibody which can bind a CD40 antigen. A light chain of an anti-CD40 antibody can be Chi Lob 7/4.
[0266] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be an IgG1 isotype. A heavy chain of an anti-CD40 antibody can be SBT-040-G1WT.
[0267] An antibody construct can comprise an antibody heavy chain. A heavy chain can be a heavy chain of an anti-CD40 antibody which can bind a CD40 antigen. A heavy chain of an anti-CD40 antibody can be an IgG1 isotype. A heavy chain of an anti-CD40 antibody can be SBT-040 VH-hIgG1 wt.
[0268] A heavy chain of an anti-CD40 antibody can be an IgG2 isotype. A heavy chain of an anti-CD40 antibody can be SBT-040-G2.
[0269] An antibody construct can comprise an antibody with modifications occurring at least at one amino acid residue. Modifications can be substitutions, additions, mutations, deletions, or the like. An antibody modification can be an insertion of an unnatural amino acid.
[0270] An antibody construct can comprise a light chain of an amino acid sequence having at least one, two, three, four, five, six, seven, eight, nine, or ten modifications but not more than 40, 35, 30, 25, 20, 15, or 10 modifications of the amino acid sequence relative to the natural or original amino acid sequence. An antibody construct can comprise a heavy chain with an amino acid sequence having at least one, two, three, four, five, six, seven, eight, nine or ten modifications but not more than 40, 35, 30, 25, 20, 15, or 10 modifications of the amino acid sequence relative to the natural or original amino acid sequence.
[0271] An antibody construct can have an Fc domain of an IgG1 isotype. An antibody construct can have an Fc domain of an IgG2 isotype. An antibody construct can have an Fc domain of an IgG3 isotype. An antibody construct can have an Fc domainof an IgG4 isotype.
An antibody construct can have an Fc domain of a hybrid isotype comprising constant regions from two or more isotypes. An antibody construct can be an anti-CD40 antibody, in which the anti-CD40 antibody can be a monoclonal human antibody comprising a wild-type sequence of an IgG1 isoform, in particular, at an Fc region of the antibody.
[0272] An antibody constructs disclosed herein can be non-natural, designed, and/or engineered.
Antibody constructs disclosed herein can be non-natural, designed, and/or engineered scaffolds comprising an antigen binding domain. Antibody constructs disclosed herein can be non-natural, designed, and/or engineered antibodies. Antibody constructs can be monoclonal antibodies.
Antibody constructs can be human antibodies. Antibody constructs can be humanized antibodies.

Antibody constructs can be monoclonal humanized antibodies. Antibody construct can be recombinant antibodies.
[0273] The Kd for binding of the Fc domain to an Fc receptor of an antibody construct as described herein can increase when the tumor antigen binding domain is bound to its tumor antigen as compared to the Kd for binding of the Fc domain to an Fc receptor of a construct as described herein when the tumor antigen binding domain is not bound to its tumor antigen. For example, an antibody construct as described herein can have a Kd for binding of the Fc domain to an Fc receptor in the presence of the binding domain that binds to an antigen on an immune cell, such as an antigen presenting cell, and the tumor target binding domain when the tumor target binding domain is bound to its tumor antigen that can be greater than or greater than about 100 nM. The Kd for binding of the Fc domain to an Fc receptor in the presence of the binding domain that binds to an antigen on an immune cell, such as an antigen presenting cell, and the tumor target binding domain when the tumor target binding domain is bound to its tumor antigen can be or can be about 100 nM, 200 nM, 300 nM, 400 nM, 500 nM, or 1000 nM. The Kd for binding of the Fc domain to an Fc receptor in the presence of the binding domain that binds to an antigen on an immune cell, such as an antigen presenting cell, and the tumor target binding domain when the tumor target binding domain is bound to its tumor antigen can be from 100 nM
to 200 nM, 100 nM to 300 nM, 100 nM to 400 nM, 100 nM to 500 nM, or 100 nM to 1000 nM.
Additionally, the antibody construct as described herein can have a Kd for binding of the Fc domain to an Fc receptor in the presence of the binding domain that binds to an antigen on an immune cell, such as an antigen presenting cell, and a tumor antigen binding domain when the tumor antigen binding domain is not bound to the tumor antigen is no greater than about 100 nM and is no greater than about 100 times a Kd for binding of the Fc domain to the Fc receptor in an absence of the binding domain that binds to an antigen on an immune cell and a tumor antigen binding domain.
[0274] The Kd for binding of the binding domain of an antibody construct as described herein that binds to an antigen on an immune cell, such as an antigen presenting cell, can increase when the tumor antigen binding domain is bound to its tumor antigen as compared to the Kd for binding of the binding domain that binds to an antigen on an immune cell when the tumor antigen binding domain is not bound to its tumor antigen. For example, an antibody construct can comprise a Kd for binding of the binding domain that binds to an antigen on an antigen presenting cell when the tumor antigen binding domain is bound to its tumor antigen can be greater than or greater than about 100nM. The Kd for binding of the binding domain that binds to an antigen on an immune cell, such as an antigen presenting cell, when the tumor antigen binding domain is bound to its tumor antigen can be or can be about 100 nM, 200 nM, 300 nM, 400 nM, 500 nM, or 1000 nM. Kd for binding of the binding domain that binds to an antigen on an immune cell when the tumor antigen binding domain is bound to its tumor antigen can be from 100 nM to 200 nM, 100 nM to 300 nM, 100 nM to 400 nM, 100 nM to 500 nM, or 100 nM to 1000 nM.
[0275] The effect of the tumor antigen binding domain and the binding domain that binds to an antigen on the immune cell together can be to cluster the antibody constructs or conjugates on cells expressing tumor antigen, and thus clustering immune cells such as antigen presenting cells around cancerous cells and at tumor sites resulting in activation of the antigen presenting cell effector functions. This can include the activation of the antigen on the antigen presenting cell when a an antibody construct is bound to its antigen, such as activation of CD40, CD47, TNFR2, DEC-205, PD-L1, CD36 mannose scavenger receptor 1, DC-SIGN, CLEC9A, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, CD38, TREM2, CSF1R, or CD32B. In some embodiments, this activation of the antigen on the antigen presenting cell only occurs when the tumor targeting antibody construct is bound to its tumor antigen. An antigen presenting cell effector function can include antibody dependent cellular cytotoxicity (ADCC) of the tumor antigen expressing cell, which can occur when a bispecific tumor targeting antibody construct is bound to its tumor antigen. In some embodiments, ADCC of the tumor antigen expressing cell only occurs with a bispecific tumor targeting antibody construct is bound to its tumor antigen.
In certain embodiments, a bispecific tumor targeting antibody construct density of greater than 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10,000 or more per cell, resulting from the bispecific tumor targeting antibody construct binding to the tumor antigen, induces signaling in the antigen presenting cell. Signaling can suitably be measured in vitro using a cell line expressing the tumor antigen bound by the target antigen binding domain, and primary antigen presenting cells isolated from a human subject. Signaling can be assessed as cytokine release, chemokine release, or increased expression of cell surface markers. In certain embodiments, a bispecific tumor targeting antibody construct density of greater than 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10,000 or more per cell, resulting from the bispecific tumor targeting antibody construct binding to the tumor antigen, induces ADCC of the cells expressing tumor antigen.
ADCC can suitably be measured in vitro using a cell line expressing the tumor antigen bound by the target antigen binding domain, and cells such as NK cells and/or macrophages isolated from a human subject. ADCC can be determined by the frequency of remaining tumor antigen expressing cells in the co-culture.
[0276] In some embodiments, the antibody constructs as described herein can specifically bind to a tumor antigen in a cluster of constructs or conjugates, and this clustering can induce a signal in an antigen presenting cell. The constructs as described herein can specifically bind to a tumor antigen in a cluster of constructs, and this clustering can induce antibody dependent cellular cytotoxicity. The constructs as described herein can specifically bind to a tumor antigen in a cluster of constructs and this clustering can result in an increased avidity for an antigen on an antigen presenting cell. The antibody constructs as described herein can specifically bind to a tumor antigen in a cluster of constructs and this clustering can result in an increased avidity of the Fc domain for an Fc receptor.
[0277] Sequences that can be used to produce antibodies for antibody constructs can include leader sequences. Leader sequences can include signal sequences. Leader sequences useful with the antibody construct and methods described herein can include, but are not limited to, an amino acid sequence comprising MRLPAQLLGLLLLWFPGSRC (SEQ ID NO: 847), MDWTWRILFLVAAATGAHS (SEQ ID NO: 848), and MRAWIFFLLCLAGRALA (SEQ ID
NO: 849).
[0278] An antibody construct can comprise an Fc region with an Fc domain. An Fc domain is a structure that can bind to Fc receptors. An antibody construct can comprise an Fc domain. Fc domains can be bound by Fc receptors (FcRs). Fc domains can be from antibodies. An Fc domain can be at least 80% homologous to an Fc domain from an antibody. An Fc region can be in a scaffold. An Fc region with an Fc domain can be in an antibody scaffold. An Fc region with an Fc domain can be in a non-antibody scaffold. An antibody construct can comprise an Fc region with an Fc domain in an antibody scaffold. An antibody construct can comprise an Fc region with an Fc domain in a non-antibody scaffold. An Fc domain can be in a scaffold. An Fc domain can be in an antibody scaffold. An Fc domain can be in a non-antibody scaffold. An antibody construct can comprise an Fc domain in an antibody scaffold. An antibody construct can comprise an Fc domain in a non-antibody scaffold. Fc domains of antibodies, including those of the present disclosure, can be bound by Fc receptors (FcRs). An Fc domain can be a portion of the Fc region of an antibody. FcRs can bind to an Fc domain of an antibody.
FcRs can bind to an Fc domain of an antibody bound to an antigen. FcRs are organized into classes (e.g., gamma (y), alpha (a) and epsilon (6)) based on the class of antibody that the FcR
recognizes. The FcaR class can bind to IgA and includes several isoforms, FcaRI (CD89) and Fcai.t.R. The FcyR class can bind to IgG and includes several isoforms, FcyRI (CD64), FcyRIIA (CD32a), FcyRIIB (CD32b), FcyRIIIA (CD16a), and FcyRIIIB (CD16b). An FcyRIIIA (CD16a) can be an FcyRIIIA
(CD16a) F158 variant. An FcyRIIIA (CD16a) can be an FcyRIIIA (CD16a) V158 variant.
Each FcyR
isoform can differ in affinity to the Fc region of the IgG antibody. For example, FcyRI can bind to IgG with greater affinity than FcyRII or FcyRIII. The affinity of a particular FcyR isoform to IgG can be controlled, in part, by a glycan (e.g., oligosacccharide) at position CH284.4 of the IgG antibody. For example, fucose containing CH284.4 glycans can reduce IgG
affinity for FcyRIIIA. In addition, GO glucans can have increased affinity for FcyRIIIA due to the lack of galactose and terminal GlcNAc moiety.
[0279] Binding of an Fc domain to an FcR can enhance an immune response. FcR-mediated signaling that can result from an Fc region binding to an FcR can lead to the maturation of immune cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can lead to the maturation of dendritic cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can lead to antibody dependent cellular cytotoxicity.
FcR-mediated signaling that can result from an Fc domain binding to an FcR can lead to more efficient immune cell antigen uptake and processing. FcR-mediated signaling that can result from an Fc region binding to an FcR can lead to more efficient dendritic cell antigen uptake and processing. FcR-mediated signaling that can result from an Fc region binding to an FcR can increase antigen presentation. FcR-mediated signaling that can result from an Fc region binding to an FcR can increase antigen presentation by immune cells. FcR-mediated signaling that can result from an Fc region binding to an FcR can increase antigen presentation by antigen presenting cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can increase antigen presentation by dendritic cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can promote the expansion and activation of T cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can promote the expansion and activation of CD8+ T cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can influence immune cell regulation of T cell responses. FcR-mediated signaling that can result from an Fc domain binding to an FcR can influence immune cell regulation of T
cell responses.
FcR-mediated signaling that can result from an Fc domain binding to an FcR can influence dendritic cell regulation of T cell responses. FcR-mediated signaling that can result from an Fc domain binding to an FcR can influence functional polarization of T cells (e.g., polarization can be toward a TH1 cell response).
[0280] The profile of FcRs on a dendritic cell (DC) can impact the ability of the DC to respond upon stimulation. For example, most DC can express both CD32A and CD32B, which can have opposing effects on IgG-mediated maturation and function of DCs: binding of IgG to CD32A can mature and activate DCs in contrast with CD32B, which can mediate inhibition due to phosphorylation of immunoreceptor tyrosine-based inhibition motif (ITIM), after CD32B binding of IgG. Therefore, the activity of these two receptors can establish a threshold of DC activation.
Furthermore, the difference in functional avidity of these receptors for IgG
can shift their functional balance. Hence, altering the Fc domain binding to FcRs can also shift their functional balance, allowing for manipulation (either enhanced activity or enhanced inhibition) of the DC
immune response.
[0281] A modification in the amino acid sequence of the Fc domain of an antibody construct can alter the recognition of an FcR for the Fc domain. However, such modifications can still allow for FcR-mediated signaling. A modification can be a substitution of an amino acid at a residue (e.g., wildtype) for a different amino acid at that residue. A modification can permit binding of an FcR to a site on the Fc domain or region that the FcR may not otherwise bind to. A modification can increase the binding affinity of an FcR to the Fc domain that the FcR may have reduced binding affinity for. A modification can decrease binding affinity of an FcR
to a site on the Fc domain that the FcR may have increased binding affinity for. A modification can increase the subsequent FcR-mediated signaling after Fc binding to an FcR.
[0282] An antibody construct can comprise an Fc region with at least one amino acid change as compared to the sequence of the wild-type Fc region. An antibody construct can comprise an Fc domain with at least one amino acid change as compared to the sequence of the wild-type Fc domain. An amino acid change in an Fc region can allow the construct to bind to at least one Fc receptor with greater affinity compared to a wild-type Fc region. An amino acid change in an Fc domain can allow the antibody construct to bind to at least one Fc receptor with greater affinity compared to a wild-type Fc domain. An Fc region can comprise an amino acid sequence having at least one, two, three, four, five, six, seven, eight, nine or ten modifications but not more than 40, 35, 30, 25, 20, 15, or 10 modifications of the amino acid sequence relative to the natural or original amino acid sequence. An Fc domain can comprise an amino acid sequence having at least one, two, three, four, five, six, seven, eight, nine or ten modifications but not more than 40, 35, 30, 25, 20, 15, or 10 modifications of the amino acid sequence relative to the natural or original amino acid sequence. An Fc region can be an Fc region of an IgG1 antibody. An Fc region can contain an Fc domain. An Fc region can be an Fc domain.
[0283] An antibody construct can be an antibody comprising a sequence of the IgG1 isoform that has been modified from the wildtype IgG1 sequence. A modification can comprise a substitution at more than one amino acid residue such as at 5 different amino acid residues including L235V/F243L/R292P/Y300L/P396L (IgG1VLPLL). The numbering of amino acids residues is according to the EU index of Kabat. The 5 amino acid residues can be located in a portion of an antibody sequence which can encode an Fc region of the antibody and in particular, can be located in portions of the Fc region that can bind to Fc receptors (i.e., the Fc domain). A
modification can comprise a substitution at more than one amino acid residue such as at 3 different amino acid residues including S298A/E333A/K334A (IgGlAAA), according to the EU
index of Kabat. The 3 amino acid residues can be located in a portion of an antibody sequence which can encode an Fc region of the antibody and in particular, can be located in portions of the Fc region that can bind Fc receptors (i.e., the Fc domain).
[0284] In some embodiments, the Fc domain or region can comprise a sequence of an IgG
isoform that has been modified from the wild-type IgG sequence. In some embodiments, the Fc domain or region can comprise a sequence of the IgG1 isoform that has been modified from the wild-type IgG1 sequence. In some embodiments, the modification comprises substitution of one or more amino acids that reduce binding affinity of an IgG Fc domain or region to all Fey receptors. A modification can be substitution of E233, L234 and L235, such as E233P/L234V/L235A or E233P/L234V/L235A/AG236, according to the EU index of Kabat. A
modification can be substitution of L235, F243, R292, Y300 and P396, such as L235V/F243L/R292P/Y300L/P396L (IgG1VLPLL) according to the EU index of Kabat.
A
modification can be a substitution of P238, such as P238A, according to the EU
index of Kabat.
A modification can be a substitution of D265, such as D265A, according to the EU index of Kabat. A modification can be a substitution of N297, such as N297A, according to the EU index of Kabat. A modification can be a substitution of A327, such as A327Q, according to the EU
index of Kabat. A modification can be a substitution of P329, such as P239A, according to the EU index of Kabat.
[0285] In some embodiments, an IgG Fc domain or region comprises at least one amino acid substitution that reduces its binding affinity to FcyR1, as compared to a wild-type or reference IgG Fc domain. A modification can comprise a substitution at F241, such as F241A, according to the EU index of Kabat. A modification can comprise a substitution at F243, such as F243A, according to the EU index of Kabat. A modification can comprise a substitution at V264, such as V264A, according to the EU index of Kabat. A modification can comprise a substitution at D265, such as D265A according to the EU index of Kabat.
[0286] In some embodiments, an IgG Fc domain or region comprises at least one amino acid substitution that increases its binding affinity to FcyR1, as compared to a wild-type or reference IgG Fc domain. A modification can comprise a substitution at A327 and P329, such as A327Q/P329A, according to the EU index of Kabat.
[0287] In some embodiments, the modification comprises substitution of one or more amino acids that reduce binding affinity of an IgG Fc domain or region to FcyRII and FcyRIIIA
receptors. A modification can be a substitution of D270, such as D270A, according to the EU
index of Kabat. A modification can be a substitution of Q295, such as Q295A, according to the EU index of Kabat. A modification can be a substitution of A327, such as A237S, according to the EU index of Kabat.
[0288] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain or region to FcyRII
and FcyRIIIA
receptors. A modification can be a substitution of T256, such as T256A, according to the EU
index of Kabat. A modification can be a substitution of K290, such as K290A, according to the EU index of Kabat.
[0289] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain or region to FcyRII
receptor. A
modification can be a substitution of R255, such as R255A, according to the EU
index of Kabat.
A modification can be a substitution of E258, such as E258A, according to the EU index of Kabat. A modification can be a substitution of S267, such as S267A, according to the EU index of Kabat. A modification can be a substitution of E272, such as E272A, according to the EU
index of Kabat. A modification can be a substitution of N276, such as N276A, according to the EU index of Kabat. A modification can be a substitution of D280, such as D280A, according to the EU index of Kabat. A modification can be a substitution of H285, such as H285A, according to the EU index of Kabat. A modification can be a substitution of N286, such as N286A, according to the EU index of Kabat. A modification can be a substitution of T307, such as T307A, according to the EU index of Kabat. A modification can be a substitution of L309, such as L309A, according to the EU index of Kabat. A modification can be a substitution of N315, such as N315A, according to the EU index of Kabat. A modification can be a substitution of K326, such as K326A, according to the EU index of Kabat. A modification can be a substitution of P331, such as P331A, according to the EU index of Kabat. A modification can be a substitution of S337, such as S337A, according to the EU index of Kabat. A
modification can be a substitution of A378, such as A378A, according to the EU index of Kabat. A
modification can be a substitution of E430, such as E430, according to the EU index of Kabat.
[0290] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain or region to FcyRII
receptor and reduces the binding affinity to FcyRIIIA receptor. A modification can be a substitution of H268, such as H268A, according to the EU index of Kabat. A modification can be a substitution of R301, such as R301A, according to the EU index of Kabat. A modification can be a substitution of K322, such as K322A, according to the EU index of Kabat.
[0291] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain or region to FcyRII
receptor but does not affect the binding affinity to FcyRIIIA receptor. A modification can be a substitution of R292, such as R292A, according to the EU index of Kabat. A modification can be a substitution of K414, such as K414A, according to the EU index of Kabat.
[0292] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain or region to FcyRII
receptor and increases the binding affinity to FcyRIIIA receptor. A modification can be a substitution of S298, such as S298A, according to the EU index of Kabat. A modification can be substitution of S239, 1332 and A330, such as S239D/1332E/A330L. A modification can be substitution of S239 and 1332, such as S239D/I332E.
[0293] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain or region to FcyRIIIA receptor and does not affect the binding affinity to FcyRII receptor. A modification can be a substitution of S239, such as S239A, according to the EU index of Kabat. A modification can be a substitution of E269, such as E269A, according to the EU index of Kabat. A modification can be a substitution of E293, such as E293A, according to the EU index of Kabat. A
modification can be a substitution of Y296, such as Y296F, according to the EU index of Kabat. A
modification can be a substitution of V303, such as V303A, according to the EU index of Kabat.
A modification can be a substitution of A327, such as A327G, according to the EU index of Kabat. A
modification can be a substitution of K338, such as K338A, according to the EU
index of Kabat.
A modification can be a substitution of D376, such as D376A, according to the EU index of Kabat.
[0294] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain or region to FcyRIIIA receptor and does not affect the binding affinity to FcyRII receptor. A modification can be a substitution of E333, such as E333A, according to the EU index of Kabat. A modification can be a substitution of K334, such as K334A, according to the EU index of Kabat. A modification can be a substitution of A339, such as A339T, according to the EU index of Kabat. A modification can be substitution of S239 and 1332, such as S239D/I332E.
[0295] In some embodiments, an IgG Fc domain or region comprises at least one amino acid substitution that reduces the binding affinity to FcRn, as compared to a wild-type or reference IgG Fc domain. A modification can comprise a substitution at H435, such as H435A according to the EU index of Kabat. A modification can comprise a substitution at 1253, such as I253A
according to the EU index of Kabat. A modification can comprise a substitution at H310, such as H310A according to the EU index of Kabat. A modification can comprise substitutions at 1253, H310 and H435, such as 1253A/H310A/H435A according to the EU index of Kabat.
[0296] A modification can comprise a substitution of one amino acid residue that increases the binding affinity of an IgG Fc domain for FcRn, relative to a wildtype or reference IgG Fc domain. A modification can comprise a substitution at V308, such as V308P
according to the EU index of Kabat. A modification can comprise a substitution at M428, such as according to the EU index of Kabat. A modification can comprise a substitution at N434, such as N434A according to the EU index of Kabat or N434H according to the EU index of Kabat. A
modification can comprise substitutions at T250 and M428, such as T250Q and according to the EU index of Kabat. A modification can comprise substitutions at M428 and N434, such as M428L and N434S, N434A or N434H according to the EU index of Kabat. A
modification can comprise substitutions at M252, S254 and T256, such as according to the EU index of Kabat. A modification can be a substitution of one or more amino acids selected from P257L, P257N, P257I, V279E, V279Q, V279Y, A281S, E283F, V284E, L306Y, T307V, V308F, Q311V, D376V, and N434H. Other substitutions in an IgG Fc domain that affect its interaction with FcRn are disclosed in U.S. Patent No.
9,803,023 (the disclosure of which is incorporated by reference herein).
[0297] An antibody construct can be a monoclonal anti-CD40 human antibody comprising a sequence of the IgG1 isoform that has been modified from the wildtype IgG1 sequence. A
modification can comprise a substitution at more than one amino acid residue such as at 5 different amino acid residues including L235V/F243L/R292P/Y300L/P396L (SBT-040-G1VLPLL). The numbering of amino acids residues is according to the EU index.
The 5 amino acid residues can be located in a portion of an antibody sequence which can encode an Fc region of the antibody and in particular, can be located in portions of the Fc region that can bind to Fc receptors (i.e., the Fc domain). A modification can comprise a substitution at more than one amino acid residue such as at 3 different amino acid residues including (SBT-040-G1AAA). The 3 amino acid residues can be located in a portion of an antibody sequence which can encode an Fc region of the antibody and in particular, can be located in portions of the Fc region that can bind Fc receptors (i.e., the Fc domain).
[0298] Binding of Fc receptors to an Fc region can be affected by amino acid substitutions. For example, SBT-040-VLPLL is an antibody with an amino acid sequence of a heavy chain of human anti-CD40 monoclonal antibody with modifications to a wild-type IgG1 Fc domain (L235V/F243L/R292P/Y300L/P396L). Binding of some Fc receptors to the Fc region of SBT-040-VLPLL can be enhanced compared to wild-type by as result of the L235V/F243L/R292P/Y300L/P396L amino acid modifications. However, binding of other Fc receptors to the Fc region of SBT-040-VLPLL can be reduced compared to wild-type by the L235V/F243L/R292P/Y300L/P396L amino acid modifications. For example, the binding affinities of SBT-040-VLPLLto FcyRIIIA and to FcyRIIA can be enhanced compared to wild-type whereas the binding affinity of SBT-040-VLPLL to FcyRIIB can be reduced compared to wild-type. Binding of Fc receptors to an Fc region of are affected by amino acid substitutions.

SBT-040-G1AAA antibody is an antibody with an amino acid sequence of a heavy chain of a human anti-CD40 monoclonal antibody with modifications to a wild-type IgG1 Fc domain (S298A/E333A/K334A). Binding of Fc receptors to an Fc region of SBT-040-G1AAA
can be enhanced compared to wild-type as a result of the S298A/E333A/K334A amino acid modification. However, binding of some Fc receptors to the Fc region of SBT-040-G1AAA can be reduced compared to wild-type by S298A/E333A/K334A amino acid modification.
Binding affinities of SBT-040-G1AAA to FcyRIIIA can be enhanced compared to wild-type whereas the binding affinity of SBT-040-G1AAA to FcyRIIB can be reduced compared to wildtype.
[0299] In some embodiments, the heavy chain of a human IgG2 antibody can be mutated at cysteines as positions 127, 232, or 233. In some embodiments, the light chain of a human IgG2 antibody can be mutated at a cysteine at position 214. The mutations in the heavy and light chains of the human IgG2 antibody can be from a cysteine residue to a serine residue.
[0300] While an antibody construct of the present disclosure can comprise a first binding domain and a second binding domain (or, in some cases, a third binding domain) with wild-type or modified amino acid sequences encoding the Fc region or Fc domain, the modifications of the Fc region or the Fc domain from the wild-type sequence may not significantly alter binding and/or affinity of the binding domains. For example, binding and/or affinity of an antibody constructcomprising a first binding domain and a second binding domain (or, in some cases, a third binding domain) and having the Fc domain modifications of SBT-040-G1WT, G1VLPLL, or SBT-040-G1AAA may not be significantly altered by modification of an Fc region or Fc domain amino acid sequence compared to a wild-type sequence.
Modifications of an Fc region or Fc domain from a wild-type sequence may not alter binding and/or affinity of a first binding domain that binds, for example, to CD40 or DEC-205. Additionally, the binding and/or affinity of the binding domains described herein, for example, a first binding domain, a second binding domain (or, in some cases, a third binding domain), and an Fc domain modification selected from SBT-040-G1WT, SBT-040-G1VLPLL, and SBT-040-G1AAA, may be comparable to the binding and/or affinity of wild-type antibodies.
[0301] In some embodiments, the binding profile of the Fc domain for Fey receptors can be retained in the antibody construct or conjugate, which can allow for delivery of the antibody construct or conjugate into immune cell types comprising the Fey receptors and can further immune activation by Fcy receptor signaling. In some embodiments, APCs can be activated by an antibody construct or conjugate as described herein when the antibody construct or conjugate is bound to a tumor cell, undergoes Fey receptor mediated uptake, or undergoes Fey receptor mediated Antibody Dependent Cellular Phagocytosis (ADCP). In some embodiments, the antibody construct or conjugate can retain weak or no Fey receptor binding to allow for maximal immune activation or decreased toxicity of the immune-stimulatory compound due to the primary delivery of the antibody construct or conjugate into tumor cells by antibody antigen mediated endocytosis.
[0302] In some embodiments, the antibody construct or conjugate can comprise an IgG1 Fc domain variant comprising N297A, N297G, K322A/L234A/L235A, or L234F/L235E/P331S, and lacks binding to an Fey receptor but can retain binding to FcRN in the presence of the immune-modulatory compound to allow for lower delivery of the conjugate into tumor cells or immune cells.
[0303] In some embodiments, an antibody construct or conjugate can comprise an Fc domain with higher affinity to one or more Fey receptors, which can result in greater immune activation than for an antibody construct or conjugate with an Fc domain that can bind to one or more Fey receptors with lower affinity.
TABLE 1. Tumor Antibody CDRs Antibody Region SEQ ID Sequence NO:
Pertuzumab HCDR1 13 GFTFTDYT

Cetuximab HCDR1 26 GFSLTNYG

Panitumumab HCDR1 39 GGSVSSGDYY

Nimotuzumab HCDR1 52 GYTFTNYY

Zalutumumab HCDR1 65 GFTFSTYG

Onartuzumab HCDR1 78 GYTFTSYW

Antibody Region SEQ ID Sequence NO:

Patritumab HCDR1 91 GGSFSGYY

Clivatuzumab HCDR1 104 GYTFPSYV

Sofituzumab HCDR1 117 GYSITNDYA

Edrecolomab HCDR1 130 GYAFTNYL

Adecatumumab HCDR1 143 GFTFSSYG

Anetumab HCDR1 156 GYSFTSYW

huDS6 HCDR1 169 GYTFTSYN

Lifastuzumab HCDR1 182 GFSFSDFA

Sacituzumab HCDR1 195 GYTFTNYG

Antibody Region SEQ ID Sequence NO:

Humanized PR1A3 HCDR1 805 GYTFTEFG

Humanized Ab2-3 HCDR1 823 GFVFSSYD

IMAB362, HCDR1 221 GYTFTSYW

Sibrotuzumab HCDR1 286 RYTFTEYT

DS-8895a variant 1 HCDR1 299 GYTFIDYS

DS-8895a variant 2 HCDR1 312 GYTFIDYS

Narnatumab HCDR1 338 GFTFSSYL

Antibody Region SEQ ID Sequence NO:

Farletuzumab HCDR1 364 GFTFSGYG

Mirvetuximab HCDR1 377 GYTFTGYF

J591 variant 1 HCDR1 390 GYTFTEYT

J591 variant 2 HCDR1 403 GYTFTEYT

Rovalpituzumab HCDR1 416 GYTFTNYG

Antibody to PTK7 HCDR1 442 GFTFSSYA

Ladiratuzumab HCDR1 455 GLTIEDYY

Antibody Region SEQ ID Sequence NO:

Cirmtuzumab HCDR1 468 GYAFTAYN

Antibody to HCDR1 481 GFRFRSHG

Antibody to NY- HCDR1 494 GFSFIDYG

Trastuzumab HCDR1 673 GFNIKDTY

Ipilumumab HCDR1 850 GFTFSSYT

Vonlerolizumab HCDR1 856 GYTFTDSY

Anti-CD27 HCDR1 862 GFTFSSYD
Antibody HCDR2 863 IWYDGSNK

Atezolizumab HCDR1 868 GFTFSDSW

Durvalumab HCDR1 874 GFTFSRYW

Antibody Region SEQ ID Sequence NO:

TABLE 2. Tumor Antibody VH sequences and VL sequences Antibody Region SEQ Sequence ID
NO:
Pertuzumab VH 12 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVA
DVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARN
LGPSFYFDYWGQGTLVTVSS

YRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKV
EIK
Cetuximab VH 25 QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY
DYEFAWGQGTLVTVSA

ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK
Panitumumab VH 38 QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKGLEWIG
HIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTG
AFDIWGQGTMVTVSS

SNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKV
EIK
Nimotuzumab VH 51 QVQLQQSGAEVKKPGS SVKVSCKASGYTFTNYYIWVRQAPGQGLEWIG
GINPTSGGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAFYFCARQGL
WFDSDGRGFDFWGQGSTVTVSS

LIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQYSHVPWTFG
QGTKLEIK
Zalutumumab VH 64 QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVA
VIWDDGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DGITMVRGVMKDYFDYWGQGTLVTVSS

SLESGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVE
IK
Onartuzumab VH 77 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGLEWVG
MIDPSNSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDTAVYYCATYR
SYVTPLDWGQGTLVTVSS

LLIWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYAYPWT
FGQGTKVEIK
Patritumab VH 90 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGLEWIGE
INHSGSTNYNPSLKSRVTISVETSKNQFSLKLS SVTAADTAVYYCARDKWT
WYFDLWGRGTLVTVSS

Antibody Region SEQ Sequence ID
NO:

LLIWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPRT
FGQGTKVEIK
Clivatuzumab VH 103 QVQLQQSGAEVKKFGAS VKVSCEASGYTFPSYVLHWVKQAPGQGLEWIG
YINPYNDGTQTNKKFKGKATLTRDTSINTAYMELSRLRSDDTAVYYCARG
FGGSYGFAYNGQGTLVTVSS

TSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWNRYPYTFGGGT
RLEIK
Sofituzumab VH 116 EVQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLEWV
GYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWT
SGLDWGQGTLVTVSS

TSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTTPFTFGQGTK
VEIK
Edrecolomab VH 129 QVQLQQSGAELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGLEWIGV
INPGSGGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDSAVYFCARDGP
WFAWGQGTLVTVSA

ASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGG
TKLEIK
Adecatumum VH 142 EVQLLESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVA
ab VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKD
MGWGSGWRPYYYYGMDVWGQGTTVTVSS

TRESGVPDRFSGSGSGTDFTLTISSLQPEDSATYYCQQSYDIPYTFGQGTKLE
IK
Anetumab VH 155 QVELVQSGAEVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLEWMGII
DPGDSRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARGQLY
GGTYMDGWGQGTLVTVSS

VNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYDIESATPVFGG
GTKLTVL
huDS6 VH 168 QAQLVQSGAEVVKPGAS VKMSCKASGYTFTSYNMHWVKQTPGQGLEWIG
YIYPGNGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDSAVYFCARGD
SVPFAWGQGTLVTVSA

LASGVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFPLTFGAGTKLE
LK
Lifastuzumab VH 181 EVQLVESGGGLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLEWVAT
IGRVAFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHR
GFDVGHFDFWGQGTLVTVSS

Antibody Region SEQ Sequence ID
NO:
LIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQGSFNPLTFG
QGTKVEIK
Sacituzumab VH

GWINTYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYFCARG
GFGSSWYFDVWGQGSLVTVSS

YRYTGVPDRFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITPLTFGAGTKV
EIK

WINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDTAKYFCARW
DFYDYVEAMDWGQGTTVTVSS

ASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCHQYYTYPLFTFGSG
TKLEMK
Humanized VH 811 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

WDFAYYVEAMDWGQGTTVTVSS

SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT
KLEIK
Humanized VH

Ab2-3 SSGGGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCAAHYF
GSSGPFAWGQGTLVTVSS

RTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGTPFTFGSGTKL
EIK
IMAB362, VH

CLAUDIXIM
IYPSDSYTNYNQKFKDKATLTVDKSSSTAYMQLS SPTSEDSAVYYCTRSWR
AB GNSFDWGQGTTLTVSS

KLLIWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSYPF
TFGSGTKLEIK

VIWYDGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARD
GYDILTGNPRDFDWGQGTLVTVSS

LIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPRTF
GQGTKVEIK

YISYNGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRG
FPWGQGTLVTVSS

NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK
LEIK
Sibrotuzumab VH

INPNNGIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTAVYYCARRRIA
YGYDEGHAMDYWGQGTLVTVSS

LLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQAEDVAVYYCQQYFSYPLT

Antibody Region SEQ Sequence ID
NO:
FGQGTKVEIK
DS-8895a VH 298 QVQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLEWM
variant 1 GWINTYTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDTAVYYCATY
YRYERDFDWGQGTLVTVSS

KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQ
GTKVEIK
DS-8895a VH 311 QIQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLKWMG
variant 2 WINTYTGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDTAVYYCATYY
RYERDFDWGQGTLVTVSS

YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFG
QGTKVEIK

RIGPSGGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGY
DSGYDYVAVAGPAEYFQHWGQGTLVTVSS

NLHTGVPSRFSGSGSGTEFSLTISGLQPDDFATYYCQQYNSYSRTFGQGTKV
EIK
Narnatumab VH 337 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLEWVA
NIKQDGSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDTAVYYCTRD
GYSSGRHYGMDVWGQGTTVIVSS

NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKV
EIK

WGDGSTDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARDYY
FNYASWFAYWGQGTLVTVSS

NLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYSELPWTFGQGTKV
EIK
Farletuzumab VH

MISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARH
GDDPAWFAWGQGTPVTVSS

NLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGT
KVEIK
Mirvetuximab VH 376 QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGR
IHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYD
GSRAMDYWGQGTTVTVSS

YRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFG
GGTKLEIK

Antibody Region SEQ Sequence ID
NO:
J591 variant 1 VH 389 EVQLQQSGPELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNIN
PNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWNF
DWGQGTTLTVSS

ASTRHTGVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQYNSYPLTFGAG
TMLDLK
J591 variant 2 VH

PNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWNF
DWGQGTTLTVSS

ASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGG
TKLEIK
Rovalpituzum VH

ab GWINTYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR
IGDSSPSDWGQGTLVTVSS

SNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTSPWTFGQGTK
LEIK

VISTYNDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTAVYYCARG
NSYFYALDYWGQGTSVTVSS

YRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSNEDPWTFGG
GTKLEIK
Antibody to VH

YFDWGQGTLVTVSS

SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQS SSLPITFGQGTRLEI
K
Ladiratuxuma VH

b GWIDPENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYCAV
HNAHYGTWFAWGQGTLVTVSS
VL

YKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGG
GTKVEIK
Cirmtuzumab VH

FDPYDGGSSYNQKFKDRLTISKDTSKNQVVLTMTNMDPVDTATYYCARG
WYYFDWGHGTLVTVSS

LQSGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPYTFGEGTKVEI
K
Antibody to VH

YTSDWQYFQWGQGTLVIVSS

Antibody Region SEQ Sequence ID
NO:

TRATGIPARFSGSGSGTEFTLTISSLQSEDLAVYYCQQSNSWPLTFGGGTKV
EIK
Antibody to VH

GMNWSGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVEDTALYFCARG
EYSNRFDPRGRGTLVTVSS
VL

IYKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYCMQGTHWPPIFG
QGTKVEIK
Trastuzumab VH

IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG
GDGFYAMDWGQGTLVTVSS

SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV
EIK
Vonlerolizum VH

ab DMYPDNGDSSYNQKFRERVTITRDTSTSTAYLELSSLRSEDTAVYYCVLAP
RWYFSVWGQGTLVTVSS

RLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGHTLPPTFGQGTKV
EIK
Varlilumab VH 888 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYDMHWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
GSGNWGFFDYWGQGTLVTVSS

SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNTYPRTFGQGTKV
EIK
Atezolizumab VH 890 EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR
HWPGGFDWGQGTLVTVSS

SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK
VEIK
Durvalumab VH 892 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRWMSWVRQAPGKGLEWVA
NIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARE
GGWFGELAFDWGQGTLVTVSS

SSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSLPWTFGQGTK
VEIK

GIIPIFGKAHYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYFCARKFH
FVSGSPFGMDVWGQGTTVTVSS

NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPTFGQGTKVE
IK
Ipilumumab VH 896 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG
WLGPFDYWGQGTLVTVSS

FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK
VEIK

GIIPIFGKAHYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYFCARKFH

Antibody Region SEQ Sequence ID
NO:
FVSGSPFGMDVWGQGTTVTVSS

NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPTFGQGTKVE
IK
TABLE 3. Tumor Antibody Heavy Chain and Light Chain sequences Antibody Region SEQ Sequence ID
NO:
Pertuzumab Heavy 11 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVA
Chain DVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARN
LGPSFYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Light 16 DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSAS
Chain YRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
Cetuximab Heavy 24 QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI
Chain WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY
DYEFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS
VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 29 DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES
Chain ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSF
NRGEC
Panitumumab Heavy 37 QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKGLEWIG
Chain HIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTG
AFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV
TVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSNFGTQTYTCNVDHK
PSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTC
VVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVH
QDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 42 DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKWYDA
Chain SNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC

Antibody Region SEQ Sequence ID
NO:
Nimotuzumab Heavy 50 QVQLQQSGAEVKKPGS SVKVSCKASGYTFTNYYIWVRQAPGQGLEWIG
Chain GINPTSGGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAFYFCARQGL
WFDSDGRGFDFWGQGSTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 55 DIQMTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPGKAPKL
Chain LIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQYSHVPWTFG
QGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
Zalutumumab Heavy 63 QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVA
Chain VIWDDGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DGITMVRGVMKDYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLF
PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE
EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT
PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSP
GK
Light 68 AIQLTQSPSSLSASVGDRVTITCRASQDISSALVWYQQKPGKAPKLLIYDAS
Chain SLESGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVE
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC
Onartuzumab Heavy 76 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGLEWVG
Chain MIDPSNSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDTAVYYCATYR
SYVTPLDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP
SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 81 DIQMTQSPSSLSASVGDRVTITCKSSQSLLYTSSQKNYLAWYQQKPGKAPK
Chain LLIWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYAYPWT
FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC LLNNFYPREAKVQW
KVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH
QGLSSPVTKSFNRGEC
Patritumab Heavy 89 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGLEWIGE
Chain INHSGSTNYNPSLKSRVTISVETSKNQFSLKLS SVTAADTAVYYCARDKWT
WYFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 94 DIEMTQSPDSLAVSLGERATINCRS SQSVLYSSSNRNYLAWYQQNPGQPPK
Chain LLIWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPRT
FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC LLNNFYPREAKVQW
KVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH
QGLSSPVTKSFNRGEC
Clivatuzumab Heavy 102 QVQLQQSGAEVKKPGAS VKVSCEASGYTFPSYVLHWVKQAPGQGLEWIG

Antibody Region SEQ Sequence ID
NO:
Chain YINPYNDGTQYNEKFKGKATLTRDTSINTAYMELSRLRSDDTAVYYCARG
FGGSYGFAWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 107 DIQLTQSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGKAPKLWIYS
Chain TSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWNRYPYTFGGGT
RLEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP
VTKSFNRGEC
Sofituzumab Heavy 115 EVQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLEWV
Chain GYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWT
SGLDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 120 DIQMTQSPSSLSASVGDRVTITCKASDLIHNWLAWYQQKPGKAPKWYGA
Chain TSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTTPFTFGQGTK
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV
TKSFNRGEC
Edrecolomab Heavy 128 QVQLQQSGAELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGLEWIGV
Chain INPGSGGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDSAVYFCARDGP
WFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 133 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYG
Chain ASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGG
TKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS
PVTKSFNRGEC
Adecatumum Heavy 141 EVQLLESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVA
ab Chain VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKD
MGWGSGWRPYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGG
TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP
REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK
TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS
LSPGK
Light 146 ELQMTQSPSS LSASVGDRVT ITCRTSQSIS SYLNWYQQKP GQPPKLLIYW
Chain ASTRESGVPD RFSGSGSGTD FTLTISSLQP EDSATYYCQQ SYDIPYTFGQ

GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV
DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK
VYACEVTHQG LSSPVTKSFN RGEC
Anetumab Heavy 154 QVELVQSGAEVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLEWMGII

Antibody Region SEQ Sequence ID
NO:
Chain DPGDSRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARGQLY
GGTYMDGWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP
SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 159 DIALTQPASVSGSPGQSITISCTGTSSDIGGYNSVSWYQQHPGKAPKLMIYG
Chain VNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYDIESATPVFGG
GTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKG
DSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGST
VEKT VAPTECS
huDS6 Heavy 167 QAQLVQSGAEVVKPGAS VKMSCKASGYTFTSYNMHWVKQTPGQGLEWIG
Chain YIYPGNGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDSAVYFCARGD
SVPFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
TPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 172 EIVLTQSPATMSASPGERVTITCSAHSSVSFMHWFQQKPGTSPKLWIYSTSS
Chain LASGVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFPLTFGAGTKLE
LKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC
Lifastuzumab Heavy 180 EVQLVESGGGLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLEWVAT
Chain IGRVAFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHR
GFDVGHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 185 DIQMTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQQKPGKAPKL
Chain LIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQGSFNPLTFG
QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
Sacituzumab Heavy 193 QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGLKWM
Chain GWINTYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYFCARG
GFGSSWYFDVWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 198 DIQLTQSPSS LSASVGDRVS ITCKASQDVS IAVAWYQQKP GKAPKLLIYS
Chain ASYRYTGVPD RFSGSGSGTD FTLTISSLQP EDFAVYYCQQ HYITPLTFGA

GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV
DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK
VYACEVTHQG LSSPVTKSFN RGEC
PR1A3 Heavy 206 QVKLQQSGPELKKPGETVKISCKASGYTFTEFGMNWVKQAPGKGLKWMG
Chain WINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDTAKYFCARW
DFYDYVEAMDWGQGTTVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCL

Antibody Region SEQ Sequence ID
NO:
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY
TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 211 DIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKALIYS
Chain ASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCHQYYTYPLFTFGSG
TKLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC
Humanized Heavy 813 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM
PR1A3 Chain GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR
WDFAYYVEAMDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV
YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 814 DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA
Chain SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP
VTKSFNRGEC
Humanized Heavy 831 EVQLQESGPGLVKPGGSLSLSCAASGFVFSS YDMSWVRQTPERGLEWVAYI
Ab2-3 Chain SSGGGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCAAHYF
GSSGPFAWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP
SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 832 DIQMTQSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSPKLLVYNT
Chain RTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGTPFTFGSGTKL
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
IMAB362, Heavy 219 QVQLQQPGAELVRPGAS VKLSCKASGYTFTSWINWVKQRPGQGLEWIGN
CLAUDIXIM Chain IYPSDSYTNYNQKFKDKATLTVDKSSSTAYMQLS SPTSEDSAVYYCTRSWR
AB GNSFDWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS
VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 224 DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPP
Chain KLLIWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSYPF
TFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH
QGLSSPVTKSFNRGEC
AMG595 Heavy 258 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKGLEWVA
Chain VIWYDGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARD
GYDILTGNPRDFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

Antibody Region SEQ Sequence ID
NO:
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV
LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 263 DTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRL
Chain LIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPRTF
GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ
GLSSPVTKSFNRGEC
ABT806 Heavy 271 EVQLQESGPGLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWMG
Chain YISYNGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRG
FPWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPV
TVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSS SLGTQTYICNVNHKP
SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE
VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT
VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 276 DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT
Chain NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV
TKSFNRGEC
Sibrotuzumab Heavy 284 QVQLVQSGAEVKKPGAS VKVSCKTSRYTFTEYTIHWVRQAPGQRLEWIGG
Chain INPNNGIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTAVYYCARRRIA
YGYDEGHAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 289 DIVMTQSPDSLAVSLGERATINCKSSQSLLYSRNQKNYLAWYQQKPGQPPK
Chain LLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQAEDVAVYYCQQYFSYPLT
FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH
QGLSSPVTKSFNRGEC
DS-8895a Heavy 297 QVQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLEWM
variant 1 Chain GWINTYTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDTAVYYCATY
YRYERDFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 302 DIVMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSPQLLIY
Chain KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQ
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC
DS-8895a Heavy 310 QIQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLKWMG
variant 2 Chain WINTYTGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDTAVYYCATYY
RYERDFDWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDY
FPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICN
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI
SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP
SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF
FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Antibody Region SEQ Sequence ID
NO:
Light 315 DVLMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSPQLLI
Chain YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFG
QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
MEDI-547 Heavy 323 EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYMMAWVRQAPGKGLEWVS
Chain RIGPSGGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGY
DSGYDYVAVAGPAEYFQHWGQGTLVTVSSASTKGPS VFPLAPSSKSTSGG
TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP
REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK
TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS
LSPGK
Light 328 DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYKAS
Chain NLHTGVPSRFSGSGSGTEFSLTISGLQPDDFATYYCQQYNSYSRTFGQGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
Narnatumab Heavy 336 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLEWVA
Chain NIKQDGSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDTAVYYCTRD
GYSSGRHYGMDVWGQGTTVIVSSASTKGPSVFPLAPS SKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 341 EIVLTQSPATLSLSPGERATLSCRASQSVSRYLAWYQQKPGQAPRLLIYDAS
Chain NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
RG7841 Heavy 349 EVQLVESGPALVKPTQTLTLTCTVSGFSLTGYSVNWIRQPPGKALEWLGMI
Chain WGDGSTDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARDYY
FNYASWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 354 DIQMTQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKTVKLLIYYTS
Chain NLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYSELPWTFGQGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
Farletuzumab Heavy 362 EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVA
Chain MISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARH
GDDPAWFAWGQGTPVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 367 DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTS

Antibody Region SEQ Sequence ID
NO:
Chain NLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGT
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP
VTKSFNRGEC
Mirvetuximab Heavy 375 QVQLVQSGAEVVKPGAS VKISCKASGYTFTGYFMNWVKQSPGQSLEWIGR
Chain IHPYDGDTFY
NQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDWG
QGTTVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPA
PELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT
KPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY
TLPPSRDELT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPG
Light 380 DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLI
Chain YRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFG
GGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
J591 variant 1 Heavy 388 EVQLQQSGPELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNIN
Chain PNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWNF
DWGQGTTLTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV
TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV
LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 393 DIVMTQSHKFMSTSVGDRVSIICKASQDVGTAVDWYQQKPGQSPKWYW
Chain ASTRHTGVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQYNSYPLTFGAG
TMLDLKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC
J591 variant 2 Heavy 401 EVQLQQSGPELVKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNIN
Chain PNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWNF
DWGQGTTLTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS
NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV
TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV
LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 406 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYG
Chain ASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGG
TKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS
PVTKSFNRGEC
Rovalpituzum Heavy 414 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWM
ab Chain GWINTYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR
IGDSSPSDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

Antibody Region SEQ Sequence ID
NO:
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
Light 419 EIVMTQSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQAPRLLIYYA
Chain SNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTSPWTFGQGTK
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV
TKSFNRGEC
PF-06647020 Heavy 427 QVQLVQSGPEVKKPGASVKVSCKASGYTFTDYAVHWVRQAPGKRLEWIG
Chain VISTYNDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTAVYYCARG
NSYFYALDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 432 EIVLTQSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKPGQAPRLLI
Chain YRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSNEDPWTFGG
GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC
Antibody to Heavy 440 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAFHWVRQAPGKGLEWVA
PTK7 Chain VISYDGSIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARTY
YFDWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEP
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNH
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 445 EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ
Chain SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQS SSLPITFGQGTRLEI

KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS
FNRGEC
Ladiratuzuma Heavy 453 QVQLVQSGAEVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQGLEWM
b Chain GWIDPENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYCAV
HNAHYGTWFAWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD
TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY
TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 458 DVVMTQSPLSLPVTLGQPASISCRSSQSLLHS SGNTYLEYFQQRPGQSPRPLI
Chain YKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGG
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS
SPVTKSFNRGEC
Cirmtuzumab Heavy 466 QVQLQESGPGLVKPSQTLSLTCTVSGYAFTAYNIHWVRQAPGQGLEWMGS
Chain FDPYDGGSSYNQKFKDRLTISKDTSKNQVVLTMTNMDPVDTATYYCARG
WYYFDWGHGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV
SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS
REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

Antibody Region SEQ Sequence ID
NO:
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 471 DIVMTQTPLSLPVTPGEPASISCRASKSISKYLAWYQQKPGQAPRLLIYSGST
Chain LQSGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPYTFGEGTKVEI
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS
FNRGEC
Antibody to Heavy 479 QVQLVESGGGVVQPGRSLRLSCTASGFRFRSHGMHWVRQAPGKGLEWVA
MAGE-A3 Chain VISYDGNNKLYADSVKGRITISRDNSKNTLFLQMNNVRAEDTAVYYCASP
YTSDWQYFQWGQGTLVIVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 484 EIVMTQSPATLSVSPGERATFSCRASQNISTTLAWYQQKPGQAPRLLIYDTS
Chain TRATGIPARFSGSGSGTEFTLTISSLQSEDLAVYYCQQSNSWPLTFGGGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
Antibody to Heavy 492 QVQLVQSGGGVVRPGGSLRLSCAASGFSFIDYGMSWVRQVPGKGLEWVA
NY-ESO-1 Chain GMNWSGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVEDTALYFCARG
EYSNRFDPRGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV
SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS
REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light Chain IYKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYCMQGTHWPPIFG
QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
Trastuzumab Heavy 681 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR
Chain IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG
GDGFYAMDWGQGTLVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 682 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA
Chain SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
TABLE 4. Fusion Sequences ¨ CD40 fusions via the heavy chain Antibody Region SEQ Sequence ID
NO:
Pertuzumab HC CD40 21 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS

Antibody Region SEQ Sequence ID
NO:
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIYNQRF
KGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SLSASVGDRVTI
TCKASQDVSIGVAWYQQKPGKAPKLLIYS ASYRYTGVPSRFSGSGSGTD
FTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKVEIK
HC tumor mAb with VADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYY
CD40 mAb CARNLGPSFYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL
ScFv GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK
TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG
QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH
NHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKAS
GYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMT
RDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SVSASVGDRVTI
TCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTD
FTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
HC tumor 845 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEW
mAb with VADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYY
CD40 mAb CARNLGPSFYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL
scFv (LH) GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK
TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG
QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH
NHYTQKSLSLSPGGGGGSGGGGSDIQMTQSPSSVSAS VGDRVTITCRAS
QGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTIS
SLQPEDFATYYCQQANIFPLTFGGGTKVEIKGGGGSGGGGSGGGGSGGG
GSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQG
LEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDT
AVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSS
Cetuximab HC CD40 34 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLKQSGPGLVQPSQ
SLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTS
RLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAWGQGT
LVTVSAGGGGSGGGGSGGGGSGGGGSDILLTQSPVILSVSPGERVSFSCR
ASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSIN
SVESEDIADYYCQQNNNWPTTFGAGTKLELK
HC tumor 35 QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWL
mAb with GVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR
CD40 mAb ALTYYDYEFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALG

Antibody Region SEQ Sequence ID
NO:
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Panitumuma HC CD40 47 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQESGPGLVKPSE
TLSLTCTVSGGSVSSGDYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSL
KSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMV
TVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQA
SQDISNYLNWYQQKPGKAPKWYDASNLETGVPSRFSGSGSGTDFTFTI
SSLQPEDIATYFCQHFDHLPLAFGGGTKVEIK
HC tumor 48 QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKGLE
mAb with WIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVR
CD40 mAb DRVTGAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLV
ScFv KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE
QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK
SLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTG
YYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIS
TAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTV
SSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQ
GIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISS
LQPEDFATYYCQQANIFPLTFGGGTKVEIK
Nimotuzuma HC CD40 60 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQSGAEVKKPG
SSVKVSCKASGYTFTNYYIWVRQAPGQGLEWIGGINPTSGGSNFNEKF
KTRVTITVDESTNTAYMELSSLRSEDTAFYFCARQGLWFDSDGRGFDF
WGQGSTVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGD
RVTITCRSSQNIVHSNGNTYLDWYQQTPGKAPKLLIYKVSNRFSGVPSRF
SGSGSGTDFTFTISSLQPEDIATYYCFQYSHVPWTFGQGTKLEIK
HC tumor 61 QVQLQQSGAEVKKPGS SVKVSCKASGYTFTNYYIWVRQAPGQGLEWI
mAb with GGINPTSGGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAFYFCAR

Antibody Region SEQ Sequence ID
NO:
CD40 mAb QGLWFDSDGRGFDFWGQGSTVTVSSASTKGPSVFPLAPSSKSTSGGTAA
ScFv LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Zalutumuma HC CD40 73 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPG
RSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVAVIWDDGSYKYYGD
SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGITMVRGVMK
DYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAIQLTQSPSSLS
ASVGDRVTITCRASQDISSALVWYQQKPGKAPKLLIYDASSLESGVPSRF
SGSESGTDFTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK
HC tumor 74 QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEW
mAb with VAVIWDDGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
CD40 mAb YCARDGITMVRGVMKDYFDWGQGTLVTVSSASTKGPSVFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP
ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL
PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGAS
VKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQK
FQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCS
YFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSA
SVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRF
SGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Onartuzuma HC CD40 86 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGYTFTSWLHWVRQAPGKGLEWVGMIDPSNSDTRFNPNF
KDRFTISADTSKNTAYLQMNSLRAEDTAVYYCATYRS YVTPLDWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SLSASVGDRVTI
TCKSSQSLLYTSSQKNYLAWYQQKPGKAPKLLIWASTRESGVPSRFSG
SGSGTDFTLTISSLQPEDFATYYCQQYYAYPWTFGQGTKVEIK
HC tumor 87 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGLEW

Antibody Region SEQ Sequence ID
NO:
mAb with VGMIDPSNSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDTAVYYC
CD40 mAb ATYRSYVTPLDWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Patritumab HC CD40 99 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQWGAGLLKPS
ETLSLTCAVYGGSFSGYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLK
SRVTISVETSKNQFSLKLSSVTAADTAVYYCARDKWTWYFDLWGRGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIEMTQSPDSLAVSLGERATINCR
SSQSVLYS SSNRNYLAWYQQNPGQPPKLLIWASTRESGVPDRFSGSGS
GTDFTLTISSLQAEDVAVYYCQQYYSTPRTFGQGTKVEIK
HC tumor 100 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGLEWI
mAb with GEINHSGSTNYNPSLKSRVTISVETSKNQFSLKLSSVTAADTAVYYCARD
CD40 mAb KWTWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
ScFv KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE
QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK
SLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTG
YYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIS
TAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTV
SSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQ
GIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISS
LQPEDFATYYCQQANIFPLTFGGGTKVEIK
Clivatuzuma HC CD40 112 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQSGAEVKKPG
ASVKVSCEASGYTFPSYVLHWVKQAPGQGLEWIGYINPYNDGTQYNEK
FKGKATLTRDTSINTAYMELSRLRSDDTAVYYCARGFGGSYGFAWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSLSASVGDRVT
MTCSASSSVSSSYLYWYQQKPGKAPKLWIYSTSNLASGVPARFSGSGSG
TDFTLTISSLQPEDSASYFCHQWNRYPYTFGGGTRLEIK

Antibody Region SEQ Sequence ID
NO:
HC tumor 113 QVQLQQSGAEVKKPGASVKVSCEASGYTFPSYVLHWVKQAPGQGLEW
mAb with IGYINPYNDGTQYNEKFKGKATLTRDTSINTAYMELSRLRSDDTAVYYC
CD40 mAb ARGFGGS YGFAWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Sofituzumab HC CD40 125 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGYSITNDYAWNWVRQAPGKGLEWVGYISYSGYTTYNPSL
KSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWTSGLDWGQGTLV
TVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKA
SDLII-INWLAWYQQKPGKAPKWYGATSLETGVPSRFSGSGSGTDFTLTI
SSLQPEDFATYYCQQWTTPFTFGQGTKVEIK
HC tumor 126 EVQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLE
mAb with WVGYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYC
CD40 mAb ARWTSGLDWGQGTLVTVSSASTKGPSVFPLAPS SKS TSGGTAALGCL
ScFv VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE
EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ
KSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT
GYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSI
STAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVT
VSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSAS VGDRVTITCRAS
QGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTIS
SLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Edrecoloma HC CD40 138 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQSGAELVRPGT
SVKVSCKASGYAFTNYLIEWVKQRPGQGLEWIGVINPGSGGTNYNEKF
KGKATLTADKSSSTAYMQLSSLTSDDSAVYFCARDGPWFAWGQGTL
VTVSAGGGGSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLT
CKASENVVTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATD

Antibody Region SEQ Sequence ID
NO:
FTLTISSVQAEDLADYHCGQGYSYPYTFGGGTKLEIK
HC tumor 139 QVQLQQSGAELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGLEWI
mAb with GVINPGSGGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDSAVYFCA
CD40 mAb RDGPWFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLV
ScFv KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE
QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ
PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY
KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK
SLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTG
YYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIS
TAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTV
SSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQ
GIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISS
LQPEDFATYYCQQANIFPLTFGGGTKVEIK
Adecatumu HC CD40 151 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mab mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGVVQPGR
SLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADS
VKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDMGWGSGWRPYY
YYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSELQMTQSPSS
LSASVGDRVTITCRTSQSISSYLNWYQQKPGQPPKLLIWASTRESGVPD
RFSGSGSGTDFTLTISSLQPEDSATYYCQQSYDIPYTFGQGTKLEIK
HC tumor 152 EVQLLESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEW
mAb with VAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
CD40 mAb CAKDMGWGSGWRPYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPG
ASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYA
QKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGV
CSYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSV
SASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Anetumab HC CD40 164 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVELVQSGAEVKKPGE
SLKISCKGSGYSFTSWIGWVRQAPGKGLEWMGIIDPGDSRTRYSPSFQ
GQVTISADKSISTAYLQWSSLKASDTAMYYCARGQLYGGTYMDGWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIALTQPASVSGSPGQSITISC

Antibody Region SEQ Sequence ID
NO:
TGTSSDIGGYNSVSWYQQHPGKAPKLMIYGVNNRPSGVSNRFSGSKSG
NTASLTISGLQAEDEADYYCSSYDIESATPVFGGGTKLTVL
HC tumor 165 QVELVQSGAEVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLEWM
mAb with GIIDPGDSRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCAR
CD40 mAb GQLYGGTYMDGWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
huDS6 HC CD40 177 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQAQLVQSGAEVVKPG
ASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGYIYPGNGATNYNQ
KFQGKATLTADPSSSTAYMQISSLTSEDSAVYFCARGDSVPFAWGQGT
LVTVSAGGGGSGGGGSGGGGSGGGGSEIVLTQSPATMSASPGERVTITC
SAHSSVSFMHWFQQKPGTSPKLWIYSTSSLASGVPARFGGSGSGTSYSL
TISSMEAEDAATYYCQQRSSFPLTFGAGTKLELK
HC tumor 178 QAQLVQSGAEVVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLE
mAb with WIGYIYPGNGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDSAVYF
CD40 mAb CARGDSVPFAWGQGTLVTVSAASTKGPSVFPLAPS SKSTSGGTAALGC
ScFv LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP
PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR
EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN
NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYT
QKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTF
TGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTS
ISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCS YFDWGQGTLV
TVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCRA
SQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTI
SSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Lifastuzuma HC CD40 190 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGFSFSDFAMSWVRQAPGKGLEWVATIGRVAFHTYYPDSM
KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARHRGFDVGHFDFWG

Antibody Region SEQ Sequence ID
NO:
QGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRV
TITCRSSETLVHSSGNTYLEWYQQKPGKAPKLLIYRVSNRFSGVPSRFSG
SGSGTDFTLTISSLQPEDFATYYCFQGSFNPLTFGQGTKVEIK
HC tumor 191 EVQLVESGGGLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLEWV
mAb with ATIGRVAFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
CD40 mAb ARHRGFDVGHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL
ScFv GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK
TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG
QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH
NHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKAS
GYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMT
RDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SVSASVGDRVTI
TCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTD
FTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Sacituzumab HC CD40 203 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQSGSELKKPGA
SVKVSCKASGYTFTNYGMNWVKQAPGQGLKWMGWINTYTGEPTYTD
DFKGRFAFSLDTSVSTAYLQIS SLKADDTAVYFCARGGFGSSWYFDV
WGQGSLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSLSASVGD
RVSITCKASQDVSIAVAWYQQKPGKAPKLLIYS ASYRYTGVPDRFSGSG
SGTDFTLTISSLQPEDFAVYYCQQHYITPLTFGAGTKVEIK
HC tumor 204 QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGLK
mAb with WMGWINTYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYF
CD40 mAb CARGGFGSSWYFDVWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ScFv ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVKLQQSGPELKKPGE
TVKISCKASGYTFTEFGMNWVKQAPGKGLKWMGWINTKTGEATYVEE

Antibody Region SEQ Sequence ID
NO:
FKGRFAFSLETSATTAYLQINNLKNEDTAKYFCARWDFYDYVEAMDY
WGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSQRFMSTSVG
DRVSVTCKASQNVGTNVAWYQQKPGQSPKALIYSASYRYSGVPDRFTG
SGSGTDFTLTISNVQSEDLAEYFCHQYYTYPLFTFGSGTKLEMK
HC tumor 217 QVKLQQSGPELKKPGETVKISCKASGYTFTEFGMNWVKQAPGKGLKW
mAb with MGWINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDTAKYFC
CD40 mAb ARWDFYDYVEAMDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTA
ScFv ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Humanized HC CD40 815 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
PR1A3 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPG
ASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWMGWINTKTGEATYV
EEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCARWDFAYYVEAM
DWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV
GDRVTITCKASAAVGTYVAWYQQKPGKAPKWYSASYRKRGVPSRFS
GSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGTKLEIK
HC tumor 816 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLE
mAb with WMGWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVY
CD40 mAb YCARWDFAYYVEAMDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGG
ScFv TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE
SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE
ALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRV
TMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDY
WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGD
RVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
HC tumor 843 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLE
mAb with WMGWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVY
CD40 mAb YCARWDFAYYVEAMDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGG
scFv (LH) TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE
SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE
ALHNHYTQKSLSLSPGGGGGSGGGGSDIQMTQSPSS VSASVGDRVTITC

Antibody Region SEQ Sequence ID
NO:
RASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFT
LTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIKGGGGSGGGGSGGGGS
GGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAP
GQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRS
DDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSS
Humanized HC CD40 833 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
Ab2-3 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLQESGPGLVKPGG
SLSLSCAASGFVFSSYDMSWVRQTPERGLEWVAYIS SGGGITYAPSTVK
GRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCAAHYFGSSGPFAWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPASLSASVGDRVTI
TCRASENIFSYLAWYQQKPGKSPKLLVYNTRTLAEGVPSRFSGSGSGTD
FSLTISSLQPEDFATYYCQHHYGTPFTFGSGTKLEIK
HC tumor 834 EVQLQESGPGLVKPGGSLSLSCAASGFVFSSYDMSWVRQTPERGLEWV
mAb with AYISSGGGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCA
CD40 mAb AHYFGSSGPFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
HC tumor 841 EVQLQESGPGLVKPGGSLSLSCAASGFVFSSYDMSWVRQTPERGLEWV
mAb with AYISSGGGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCA
CD40 mAb AHYFGSSGPFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
scFv (LH) CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSDIQMTQSPS SVSASVGDRVTITCRASQGIY
SWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQP
EDFATYYCQQANIFPLTFGGGTKVEIKGGGGSGGGGSGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEW
MGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVY
YCARDQPLGYCTNGVCSYFDWGQGTLVTVSS
IMAB362, HC CD40 229 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
CLAUDIXI mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
MAB tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS

Antibody Region SEQ Sequence ID
NO:
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQPGAELVRPG
ASVKLSCKASGYTFTSWINWVKQRPGQGLEWIGNIYPSDSYTNYNQK
FKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRSWRGNSFDYWGQG
TTLTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPSSLTVTAGEKVTM
SCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLLIWAS TRESGVPDRFTG
SGSGTDFTLTISSVQAEDLAVYYCQNDYSYPFTFGSGTKLEIK
HC tumor 230 QVQLQQPGAELVRPGAS VKLSCKASGYTFTSWINWVKQRPGQGLEWI
mAb with GNIYPSDSYTNYNQKFKDKATLTVDKSSSTAYM
CD40 mAb QLSSPTSEDSAVYYCTRSWRGNSFDWGQGTTLTVSSASTKGPSVFPLA
ScFv PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSS VVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS
NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP
SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV
FSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKP
GAS VKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNY
AQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNG
VCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSS
VSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVP
SRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQSG
RSLRLSCAASGFTFRNYGMHWVRQAPGKGLEWVAVIWYDGSDKYYA
DSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPR
DFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDTVMTQTPLSSH
VTLGQPASISCRS SQSLVHSDGNTYLSWLQQRPGQPPRLLIYRISRRFSGV
PDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPRTFGQGTKVEIK
HC tumor 269 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKGLEW
mAb with VAVIWYDGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYY
CD40 mAb CARDGYDILTGNPRDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG
ScFv GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV
TVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE
SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE
ALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRV
TMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDY
WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGD
RVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

Antibody Region SEQ Sequence ID
NO:
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLQESGPGLVKPSQ
TLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWMGYISYNGNTRYQPSLK
SRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRGFPWGQGTLVTV
SSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSMSVSVGDRVTITCHSSQ
DINSNIGWLQQKPGKSFKGLIYHGTNLDDGVPSRFSGSGSGTDYTLTISS
LQPEDFATYYCVQYAQFPWTFGGGTKLEIK
HC tumor 282 EVQLQESGPGLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWM
mAb with GYISYNGNTRYQPSLKSRITISRDTSKNQFFLKLNS VTAADTATYYCVTA
CD40 mAb SRGFPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY
ScFv FPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL
SLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYY
MHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTA
YMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSS
GGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGI
YSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQANIFPLTFGGGTKVEIK
Sibrotuzuma HC CD40 294 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPG
ASVKVSCKTSRYTFTEYTIHWVRQAPGQRLEWIGGINPNNGIPNYNQKF
KGRVTITVDTSASTAYMELSSLRSEDTAVYYCARRRIAYGYDEGHAMD
YWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSL
GERATINCKSSQSLLYSRNQKNYLAWYQQKPGQPPKLLIFWASTRESGV
PDRFSGSGFGTDFTLTISSLQAEDVAVYYCQQYFSYPLTFGQGTKVEIK
HC tumor 295 QVQLVQSGAEVKKPGASVKVSCKTSRYTFTEYTIHWVRQAPGQRLEWI
mAb with GGINPNNGIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTAVYYCA
CD40 mAb RRRIAYGYDEGHAMDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGG
ScFv TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT
VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG
GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH
NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE
SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE
ALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSC
KASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRV
TMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDY
WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGD
RVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
DS-8895a HC CD40 307 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
variant 1 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

Antibody Region SEQ Sequence ID
NO:
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPG
ASVKVSCKASGYTFIDYSMHWVRQAPGQGLEWMGWINTYTGEPTYSD
DFKGRVTITADTSTSTAYLELSSLRSEDTAVYYCATYYRYERDFDWG
QGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPAS
ISCRSSQSIVHS SGITYLEWYLQKPGQSPQLLIYKVSNRFSGVPDRFSGSG
SGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGTKVEIK
HC tumor 308 QVQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLEW
mAb with MGWINTYTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDTAVYYC
CD40 mAb ATYYRYERDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
DS-8895a HC CD40 320 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
variant 2 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQIQLVQSGAEVKKPGA
SVKVSCKASGYTFIDYSMHWVRQAPGQGLKWMGWINTYTGEPTYSDD
FKGRFAFSLDTSTSTAYLELSSLRSEDTAVYYCATYYRYERDFDWGQ
GTLVTVSSGGGGSGGGGSGGGSGGGGSDVLMTQSPLSLPVTPGEPASIS
CRSSQSIVHS SGITYLEWYLQKPGQSPQLLIYKVSNRFSGVPDRFSGSGS
GTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGTKVEIK
HC tumor 321 QIQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLKW
mAb with MGWINTYTGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDTAVYYC
CD40 mAb ATYYRYERDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

Antibody Region SEQ Sequence ID
NO:
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGG
SLRLSCAASGFTFSHYMMAWVRQAPGKGLEWVSRIGPSGGPTHYADSV
KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGYDSGYDYVAVAGP
AEYFQHWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSL
SASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYKASNLHTGVPS
RFSGSGSGTEFSLTISGLQPDDFATYYCQQYNSYSRTFGQGTKVEIK
HC tumor 334 EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYMMAWVRQAPGKGLEW
mAb with VSRIGPSGGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
CD40 mAb AGYDSGYDYVAVAGPAEYFQHWGQGTLVTVSSASTKGPSVFPLAPSSK
ScFv STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP
ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL
PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGAS
VKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQK
FQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCS
YFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSA
SVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRF
SGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Narnatumab HC CD40 346 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGFTFSSYLMTWVRQAPGKGLEWVANIKQDGSEKYYVDSV
KGRFTISRDNAKNSLNLQMNSLRAEDTAVYYCTRDGYSSGRHYGMDV
WGQGTTVIVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGER
ATLSCRASQSVSRYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGS
GTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGQGTKVEIK
HC tumor 347 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLEWV
mAb with ANIKQDGSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDTAVYYC
CD40 mAb TRDGYSSGRHYGMDVWGQGTTVIVSSASTKGPSVFPLAPSSKSTSGGTA
ScFv ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP

Antibody Region SEQ Sequence ID
NO:
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGPALVKPTQ
TLTLTCTVSGFSLTGYSVNWIRQPPGKALEWLGMIWGDGSTDYNSALK
SRLTISKDTSKNQVVLTMTNMDPVDTATYYCARDYYFNYASWFAYWG
QGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRV
TITCSASQGISNYLNWYQQKPGKTVKLLIYYTSNLHSGVPSRFSGSGSGT
DYTLTISSLQPEDFATYYCQQYSELPWTFGQGTKVEIK
HC tumor 360 EVQLVESGPALVKPTQTLTLTCTVSGFSLTGYSVNWIRQPPGKALEWLG
mAb with MIWGDGSTDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCA
CD40 mAb RDYYFNYASWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAA
ScFv LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Farletuzuma HC CD40 372 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGVVQPG
RSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADS
VKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAWG
QGTPVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSLSASVGDRVT
ITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGT
DYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK
HC tumor 373 EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWV
mAb with AMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCA
CD40 mAb RHGDDPAWFAWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Mirvetuxima HC CD40 385 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS

Antibody Region SEQ Sequence ID
NO:
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVVKPG
ASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQK
FQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQ
GTTVTVSSGGGGSGGGGSGGGGSGGGGSDIVLTQSPLSLAVSLGQPAIIS
CKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSG
SKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK
HC tumor 386 QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWI
mAb with GRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYC
CD40 mAb TRYDGSRAMDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
ScFv CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHY
TQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYT
FTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDT
SISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTL
VTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVS ASVGDRVTITCR
ASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTL
TISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

variantl mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLQQSGPELKKPGT
SVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNINPNNGGTTYNQKFE
DKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWNFDWGQGTTLT
VSSGGGGSGGGGSGGGGSGGGGSDIVMTQSHKFMSTSVGDRVSIICKAS
QDVGTAVDWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDFTLT
ITNVQSEDLADYFCQQYNSYPLTFGAGTMLDLK
HC tumor 399 EVQLQQSGPELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIG
mAb with NINPNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCA
CD40 mAb AGWNFDWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
ScFv DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK
TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
LSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGY
YMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIST
AYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVS
SGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SVSASVGDRVTITCRASQG
IYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQANIFPLTFGGGTKVEIK
J591 variant HC CD40 411 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
2 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS

Antibody Region SEQ Sequence ID
NO:
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLQQSGPELVKPGT
SVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNINPNNGGTTYNQKFE
DKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWNFDWGQGTTLT
VSSGGGGSGGGGSGGGGSGGGGSNIVMTQSPKSMSMSVGERVTLTCKA
SENVVTYVSWYQQKPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLT
ISSVQAEDLADYHCGQGYSYPYTFGGGTKLEIK
HC tumor 412 EVQLQQSGPELVKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIG
mAb with NINPNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCA
CD40 mAb AGWNFDWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
ScFv DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP
REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK
TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS
LSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGY
YMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIST
AYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVS
SGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SVSASVGDRVTITCRASQG
IYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSL
QPEDFATYYCQQANIFPLTFGGGTKVEIK
Rovalpituzu HC CD40 424 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mab mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPG
ASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWINTYTGEPTYA
DDFKGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARIGDSSPSDWG
QGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERAT
LSCKASQSVSNDVVWYQQKPGQAPRLLIYYASNRYTGIPARFSGSGSGT
EFTLTISSLQSEDFAVYYCQQDYTSPWTFGQGTKLEIK
HC tumor 425 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLE
mAb with WMGWINTYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDDTAV
CD40 mAb YYCARIGDSSPSDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL
ScFv GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK
TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG
QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH
NHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKAS
GYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMT
RDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SVSASVGDRVTI
TCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTD
FTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

06647020 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV

Antibody Region SEQ Sequence ID
NO:
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGPEVKKPG
ASVKVSCKASGYTFTDYAVHWVRQAPGKRLEWIGVISTYNDYTYNNQ
DFKGRVTMTRDTSASTAYMELSRLRSEDTAVYYCARGNSYFYALDYW
GQGTSVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERA
TLSCRASESVDSYGKSFMHWYQQKPGQAPRLLIYRASNLESGIPARFSG
SGSGTDFTLTISSLEPEDFAVYYCQQSNEDPWTFGGGTKLEIK
HC tumor 438 QVQLVQSGPEVKKPGASVKVSCKASGYTFTDYAVHWVRQAPGKRLEW
mAb with IGVISTYNDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTAVYY
CD40 mAb CARGNSYFYALDWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAAL
ScFv GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK
TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS
KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG
QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH
NHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKAS
GYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMT
RDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQ
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS SVSASVGDRVTI
TCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTD
FTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Antibody to HC CD40 450 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
PTK7 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPG
RSLRLSCAASGFTFSSYAFHWVRQAPGKGLEWVAVISYDGSIKYYADSV
KGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARTYYFDWGQGTLV
TVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPDFQSVTPKEKVTITCRA
SQSIGSSLHWYQQKPDQSPKLLIKYASQSFSGVPSRFSGSGSGTDFTLTIN
SLEAEDAAAYYCHQSSSLPITFGQGTRLEIK
HC tumor 451 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAFHWVRQAPGKGLEWV
mAb with AVISYDGSIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
CD40 mAb RTYYFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD
ScFv YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK
DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR
EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL
SLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYY
MHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTA
YMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSS
GGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGI
YSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQ
PEDFATYYCQQANIFPLTFGGGTKVEIK

Antibody Region SEQ Sequence ID
NO:
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPG
ASVKVSCKASGLTIEDYYMHWVRQAPGQGLEWMGWIDPENGDTEYGP
KFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYCAVHNAHYGTWFAY
WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPLSLPVTLG
QPASISCRSSQSLLHSSGNTYLEYFQQRPGQSPRPLIYKISTRFSGVPDRFS
GSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGGGTKVEIK
HC tumor 464 QVQLVQSGAEVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQGLEW
mAb with MGWIDPENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYY
CD40 mAb CAVHNAHYGTWFAWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA
ScFv ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP
SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Cirmtuzuma HC CD40 476 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
b mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQESGPGLVKPSQ
TLSLTCTVSGYAFTAYNIHWVRQAPGQGLEWMGSFDPYDGGSSYNQKF
KDRLTISKDTSKNQVVLTMTNMDPVDTATYYCARGWYYFDWGHGT
LVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQTPLSLPVTPGEPASISC
RASKSISKYLAWYQQKPGQAPRLLIYSGSTLQSGIPPRFSGSGYGTDFTL
TINNIESEDAAYYFCQQHDESPY TFGEGTKVEIK
HC tumor 477 QVQLQESGPGLVKPSQTLSLTCTVSGYAFTAYNIHWVRQAPGQGLEWM
mAb with GSFDPYDGGSSYNQKFKDRLTISKDTSKNQVVLTMTNMDPVDTATYYC
CD40 mAb ARGWYYFDWGHGTLVTVSSASTKGPS VFPLAPSSKS TSGGTAALGCL
ScFv VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT
QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE
EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG
QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ
KSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT
GYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSI
STAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVT
VSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSAS VGDRVTITCRAS
QGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTIS
SLQPEDFATYYCQQANIFPLTFGGGTKVEIK

Antibody Region SEQ Sequence ID
NO:
Antibody to HC CD40 489 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
MAGE-A3 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPG
RSLRLSCTASGFRFRSHGMHWVRQAPGKGLEWVAVISYDGNNKLYAD
SVKGRITISRDNSKNTLFLQMNNVRAEDTAVYYCASPYTSDWQYFQYW
GQGTLVIVSSGGGGSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERA
TFSCRASQNISTTLAWYQQKPGQAPRLLIYDTSTRATGIPARFSGSGSGT
EFTLTISSLQSEDLAVYYCQQSNSWPLTFGGGTKVEIK
HC tumor 490 QVQLVESGGGVVQPGRSLRLSCTASGFRFRSHGMHWVRQAPGKGLEW
mAb with VAVISYDGNNKLYADSVKGRITISRDNSKNTLFLQMNNVRAEDTAVYY
CD40 mAb CASPYTSDWQYFQWGQGTLVIVSSASTKGPSVFPLAPSSKSTSGGTAA
ScFv LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Antibody to HC CD40 502 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
NY-ESO-1 mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGGGVVRPG
GSLRLSCAASGFSFIDYGMSWVRQVPGKGLEWVAGMNWSGDKKGHA
ESVKGRFIISRDNAKNTLYLEMSSLRVEDTALYFCARGEYSNRFDPRGR
GTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQTPLSLPVTLGQPASL
SCRSSQSLVFTDGNTYLNWFQQRPGQSPRRLIYKVSSRDPGVPDRFSGT
GSGTDFTLEISRVEAEDIGVYYCMQGTHWPPIFGQGTKVEIK
HC tumor 503 QVQLVQSGGGVVRPGGSLRLSCAASGFSFIDYGMSWVRQVPGKGLEW
mAb with VAGMNWSGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVEDTALYF
CD40 mAb CARGEYSNRFDPRGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC
ScFv LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG
TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP
PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR
EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN
NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYT
QKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTF
TGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTS
ISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLV
TVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRA
SQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTI

Antibody Region SEQ Sequence ID
NO:
SSLQPEDFATYYCQQANIFPLTFGGGTKVEIK
Trastuzumab HC CD40 683 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSV
KGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDR
VTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRS
GTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK
HC tumor 684 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWV
mAb with ARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYC
CD40 mAb SRWGGDGFYAMDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAA
ScFv LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS
SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN
GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL
HNHYTQKSLSLSPGGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCK
ASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVT
MTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDYW
GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDR
VTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGS
GTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKVEIK

mAb with WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
tumor mAb YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
(LH,25mer) LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK
ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD
IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSDIQMTQSPSSLSASVG
DRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGS
RSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGG
GSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIKD
TYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTA
YLQMNSLRAEDTAVYYCSRWGGDGFYAMDWGQGTLVTVSS
TABLE 5. APC Antibody CDRs Antibody Region SEQ ID NO: Sequence SBT-040 (G1/G2) HCDR1 3 GYTFTGYY

Antibody Region SEQ ID NO: Sequence Dacetuzumab HCDR1 582 GYSFTGYY

Bleselumab HCDR1 592 GGSISSPGYY

lucatumumab HCDR1 602 GFTFSSYG

Chi Lob 7/4 HCDR1 632 GYTFTEYI

DEC-205 variant 1 HCDR1 234 GFTFSNYG

DEC-205 variant 2 HCDR1 247 GDSFTTYW

DC-SIGN variant 1 HCDR1 640 QHFWNTPWT

DC-SIGN variant 2 HCDR1 646 YYGIYVDY

Antibody Region SEQ ID NO: Sequence DC-SIGN variant 3 HCDR1 652 QQGNTLPPT

TABLE 6. APC Antibody VH sequences and VL sequences Antibody Region SEQ Sequence ID
NO:

GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCAR
DQPLGYCTNGVCSYFDWGQGTLVTVSS

STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKV
EIK

GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCAR
DQPLGYCTNGVCSYFDWGQGTLVTVSS

STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKV
EIK
Dacetuzumab VH 581 EVQLVESGGGLVQPGGSLRLSCAASGYSFTGYYTHWVRQAPGKGLEWVAR
VIPNAGGTSYNQKFKGRFTLSVDNSKNTAYLQMNSLRAEDTAVYYCAREG
IYWWGQGTLVTVSS

LIYTVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCSQTTHVPWTFG
QGTKVEIK
Bleselumab VH 591 QLQLQESGPGLLKPSETLSLTCTVSGGSISSPGYYGGWIRQPPGKGLEWIGSI
YKSGSTYHNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCTRPVVRY
FGWFDPWGQGTLVTVSS

NLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPTFGQGTKVEI
K
Lucatumuma VH 601 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVA
b VISYEESNRYHADSVKGRFTISRDNSKITLYLQMNSLRTEDTAVYYCARDG
GIAAPGPDWGQGTLVTVSS

ISLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQARQTPFTFG
PGTKVDIR

ISGGSSYIFYADSVRGRFTISRDNSENALYLQMNSLRAEDTAVYYCARILRG
GSGMDLWGQGTLVTVSS

NINRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDKSISGLVFGG
GTKLTVL

YTGDGTNYSASWAKGRFTISKDSSKNTVYLQMNSLRAEDTAVYFCARPDI
TYGFAINFWGPGTLVTVSS

TLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQCTGYGISWPIGGGTK

Antibody Region SEQ Sequence ID
NO:
VEIK
Chi Lob 7/4 VH 631 EVQLQQSGPDLVKPGASVKISCKTSGYTFTEYIMHWVKQSHGKSLEWIGGI
IPNNGGTSYNQKFKDKATMTVDKSSSTGYMELRSLTSEDSAVYYCTRREV
YGRNYYALDWGQGTLVTVSS

SLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYYCQQYSNLPYTFGGGTKLE
IK

variant 1 DLWGWYFDWGQGTLVTVSS

NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFGGGTKV
EIK

variant 2 VDWGQGTLVTVSS

SLQSGVPSRFSGSGSGTDFTLTISGLQPEDFATYYCQQYNSYPRTFGQGTKV
EIK

mannose EIK
Scavenger VL 659 EVQLVQSGAEVKKPGESLRISCKGSGDSFTTWIGWVRQMPGKGLEWMGI
Receptor IYPGDSDTIYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCTRGDRG
VDWGQGTLVTVSS

DVPFWGQGVMVTVSS

PKLLIWASTGESGVPDRFIGSGSGTDFTLTISSVQAEDLAVYYCQQYYDFP
PTFGGGTK
TABLE 7. APC Antibody Heavy Chain and Light Chain sequences Antibody Region SEQ Sequence ID
NO:
CP-8709893 Heavy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
Chain GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCAR
DQPLGYCTNGVCSYFDWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS
NFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ
VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPML
DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 6 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTA
Chain STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
SBT-040 Heavy 577 MDWTWRILFLVAAATGAHSQVQLVQSGAEVKKPGASVKVSCKASGYTFT
Chain GYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIST
(IgG1) AYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVEPKSCD
KTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC

Antibody Region SEQ Sequence ID
NO:
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY
PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS
CSVMHEALHNHYTQKSLSLSPGK
Heavy 578 MDWTWRILFLVAAATGAHSQVQLVQSGAEVKKPGASVKVSCKASGYTFT
Chain GYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSIST
(IgG2) AYMELNRLRSDDTAVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCV
ECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNW
YVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNK
GLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIA
VEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM
HEALHNHYTQKSLSLSPGK
Light 579 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTA
Chain STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
Dacetuzumab Heavy 580 EVQLVESGGGLVQPGGSLRLSCAASGYSFTGYYTHWVRQAPGKGLEWVAR
Chain VIPNAGGTSYNQKFKGRFTLSVDNSKNTAYLQMNSLRAEDTAVYYCAREG
WWWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV
TVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSS SLGTQTYICNVNHKP
SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE
VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT
VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 585 DIQMTQSPSSLSASVGDRVTITCRSSQSLVHSNGNTFLHWYQQKPGKAPKL
Chain LIYTVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCSQTTHVPWTFG
QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
Bleselumab Heavy 590 QLQLQESGPGLLKPSETLSLTCTVSGGSISSPGYYGGWIRQPPGKGLEWIGSI
Chain YKSGSTYHNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCTRPVVRY
FGWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNV
DHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTP
EVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVL
TVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
Light 595 AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDAS
Chain NLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPTFGQGTKVEI
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS
FNRGEC
Lucatumuma Heavy 600 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVA
b Chain VISYEESNRYHADSVKGRFTISRDNSKITLYLQMNSLRTEDTAVYYCARDG
GIAAPGPDWGQGTLVTVSSASTKGPSVFPLAPASKS TSGGTAALGCLVKD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC
NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP
PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 605 DIVMTQSPLSLTVTPGEPASISCRSSQSLLYSNGYNYLDWYLQKPGQSPQVL
Chain ISLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQARQTPFTFG
PGTKVDIRRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV

Antibody Region SEQ Sequence ID
NO:
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG
LSSPVTKSFNRGEC
ADC-1013 Heavy 610 EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWLSY
Chain ISGGSSYIFYADSVRGRFTISRDNSENALYLQMNSLRAEDTAVYYCARILRG
GSGMDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
TPEVTCNAVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 615 QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYNVWYQQLPGTAPKWYG
Chain NINRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDKSISGLVFGG
GTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKA
DSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGST
VEKTVAPTECS
APX005 Heavy 620 QVQLVESGGGVVQPGRSLRLSCAASGFSFSSTYVCWVRQAPGKGLEWIACI
Chain YTGDGTNYSASWAKGRFTISKDSSKNTVYLQMNSLRAEDTAVYFCARPDI
TYGFAINFWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMIS
RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV
SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS
REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 625 DIQMTQSPSSLSASVGDRVTIKCQASQSISSRLAWYQQKPGKPPKLLIYRAS
Chain TLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQCTGYGISWPIGGGTK
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV
TKSFNRGEC
Chi Lob 7/4 Heavy 630 EVQLQQSGPDLVKPGASVKISCKTSGYTFTEYIMHWVKQSHGKSLEWIGGI
Chain IPNNGGTSYNQKFKDKATMTVDKSSSTGYMELRSLTSEDSAVYYCTRREV
YGRNYYALDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 635 DIQMTQTTSSLSASLGDRVTITCSASQGINNYLNWYQQKPDGTVKLLIYYTS
Chain SLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYYCQQYSNLPYTFGGGTKLE
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC
DEC-205 Heavy 232 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
(variant 1) Chain VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 237 EIVLTQSPATLSLSPGERATLSCRASQSVS SYLAWYQQKPGQAPRLLIYDAS
Chain NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFGGGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

Antibody Region SEQ Sequence ID
NO:
KSFNRGEC
DEC-205 Heavy 245 EVQLVQSGAEVKKPGESLRISCKGSGDSFTTWIGWVRQMPGKGLEWMGI
(variant 2) Chain IYPGDSDTIYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCTRGDRG
VDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV
TVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSS SLGTQTYICNVNHKP
SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE
VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT
VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 250 DIQMTQSPSSLSASVGDRVTITCRASQGISRWLAWYQQKPEKAPKSLIYAAS
Chain SLQSGVPSRFSGSGSGTDFTLTISGLQPEDFATYYCQQYNSYPRTFGQGTKV
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
CLEC12A Heavy 662 QVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIGE
Chain IYHSGSPDYNPSLKSRVTISVDKSRNQFSLKLSSVTAADTAVYYCAKVSTG
variant GFFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Heavy 663 QVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIGE
Chain IYHSGSPNYNPSLKSRVTISVDKSKNQFSLKLS SVTAADTAVYYCARSSSGG
variant FFDWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEP

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Heavy 664 QVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIGE
Chain IYHSGSPNYNPSLKSRVTISVDKSKNQFSLKLS SVTAADTAVYYCARQTTA
variant GSFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT
PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 665 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAAS
Chain SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTKVE
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK
SFNRGEC
BDCA-2 Heavy 666 QVQLVESGGGVVQPGRSLRLSCAASGFTLS SYGMHWVRQAPGKGLEWVA
Variant 1 Chain VIWYDGNDKYYADSVKGRFTISRDNSKNTLYLQVNSLRAEDTAVYYCAR
GTGTPWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 669 EIVLTQSPATLSLSPGERATLSCRASQSVNNYLAWYQQKPGQAPRLLIYDAS
Chain NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSTWPPYTFGQGTK
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

Antibody Region SEQ Sequence ID
NO:
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV
TKSFNRGEC
BDCA-2 Heavy 667 EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYLMNWVRQAPGKGLEWVA
Variant 2 Chain NIEQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYFCARD
GDTAMITFDFWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 670 DIQMTQSPSSVSASVGDRVTITCRASQGIRRWLAWYQQKPGKAPKLLIYAA
Chain SSLQRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPWTFGQGTK
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV
TKSFNRGEC
BDCA-2 Heavy 668 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYWNWIRQHPGKGLEWIG
Variant 3 Chain YIYYSGNTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADAAVYHCARGYG
DYGGGYFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYI
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light 671 DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKFLIYDVS
Chain NLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKL
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGEC
TABLE 8. Fusion Sequences ¨ DEC-205 fusions via the heavy chain Antibody Region SEQ Sequence ID
NO:
Pertuzumab HC DEC-205 505 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLE
WVADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDT
AVYYCARNLGPSFYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSDIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGK
APKLLIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ
YYIYPYTFGQGTKVEIK
HC tumor 506 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGL
mAb with EWVADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAED
DEC-205 mAb TAVYYCARNLGPSFYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP

Antibody Region SEQ Sequence ID
NO:
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
LC tumor 846 DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKL
mAb LIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIY
containing PYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mab EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
scFv (LH) KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSDIQMTQSPS
SVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQ
SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTK
VEIKGGGGSGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVS
CKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKF
QGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGV
CSYFDWGQGTLVTVSS
Cetuximab HC DEC-205 507 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEW
LGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYY
CARALTYYDYEFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGG
SDILLTQSPVILS VSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLI
KYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPT
TFGAGTKLELK
HC tumor 508 QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLE
mAb with WLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAI
DEC-205 mAb YYCARALTYYDYEFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTS
ScFv GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC
PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQV
QLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Panitumumab HC DEC-205 509 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP

Antibody Region SEQ Sequence ID
NO:
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKGL
EWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLS S VTAADTAIY
YCVRDRVTGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGS
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKL
LIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLP
LAFGGGTKVEIK
HC tumor 510 QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKG
mAb with LEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLS
SVTAADTAI
DEC-205 mAb YYCVRDRVTGAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGG
ScFv TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ S SGLYS LS S
VVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQ SVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Nimotuzumab HC DEC-205 511 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPS S KS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQQSGAEVKKPGSS VKVSCKASGYTFTNYYIWVRQAPGQGLE
WIGGINPTSGGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAF
YFCARQGLWFDSDGRGFDFWGQGSTVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWY
QQTPGKAPKLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIAT
YYCFQYSHVPWTFGQGTKLEIK
HC tumor 512 QVQLQQSGAEVKKPGS SVKVSCKASGYTFTNYYIWVRQAPGQGL
mAb with EWIGGINPTSGGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAF
DEC-205 mAb YFCARQGLWFDSDGRGFDFWGQGSTVTVSSASTKGPSVFPLAPS SK
ScFv STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC
PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK

Antibody Region SEQ Sequence ID
NO:
Zalutumumab HC DEC-205 513 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLE
WVAVIWDDGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDGITMVRGVMKDYFDYWGQGTLVTVSSGGGGSGGGGS
GGGGSGGGGSAIQLTQSPSSLSASVGDRVTITCRASQDISSALVWYQ
QKPGKAPKLLIYDASSLESGVPSRFSGSESGTDFTLTISSLQPEDFATY
YCQQFNSYPLTFGGGTKVEIK
HC tumor 514 QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGL
mAb with EWVAVIWDDGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAED
DEC-205 mAb TAVYYCARDGITMVRGVMKDYFDWGQGTLVTVSS ASTKGPSVFP
ScFv LAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS
HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ
DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGG
GGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWV
RQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQ
MNSLRAEDTAVYYCARDLWGWYFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLA
WYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPED
FAVYYCQQRRNWPLTFGGGTKVEIK
Onartuzumab HC DEC-205 515 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGLE
WVGMIDPSNSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDTA
VYYCATYRSYVTPLDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSDIQMTQSPSSLSASVGDRVTITCKSSQSLLYTSSQKNYLAWYQQ
KPGKAPKLLIWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQYYAYPWTFGQGTKVEIK
HC tumor 516 EVQLVESGGGLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGL
mAb with EWVGMIDPSNSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDT
DEC-205 mAb AVYYCATYRSYVTPLDWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE

Antibody Region SEQ Sequence ID
NO:
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Patritumab HC DEC-205 517 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQQWGAGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGLE
WIGEINHSGSTNYNPSLKSRVTISVETSKNQFSLKLSSVTAADTAVY
YCARDKWTWYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSGGGGS
DIEMTQSPDSLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNP
GQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYY
CQQYYSTPRTFGQGTKVEIK
HC tumor 518 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGL
mAb with EWIGEINHSGSTNYNPSLKSRVTISVETSKNQFSLKLSSVTAADTAV
DEC-205 mAb YYCARDKWTWYFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSG
ScFv GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Clivatuzumab HC DEC-205 519 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQQSGAEVKKPGASVKVSCEASGYTFPSYVLHWVKQAPGQGLE
WIGYINPYNDGTQYNEKFKGKATLTRDTSINTAYMELSRLRSDDTA
VYYCARGFGGSYGFAWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSDIQLTQSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGK
APKLWIYSTSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQ
WNRYPYTFGGGTRLEIK
HC tumor 520 QVQLQQSGAEVKKPGASVKVSCEASGYTFPSYVLHWVKQAPGQGL
mAb with EWIGYINPYNDGTQYNEKFKGKATLTRDTSINTAYMELSRLRSDDT
DEC-205 mAb AVYYCARGFGGSYGFAWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

Antibody Region SEQ Sequence ID
NO:
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Sofituzumab HC DEC-205 521 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGL
EWVGYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAV
YYCARWTSGLDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSD
IQMTQSPSSLSASVGDRVTITCKASDLII-INWLAWYQQKPGKAPKLLI
YGATSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTTP
FTFGQGTKVEIK
HC tumor 522 EVQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKG
mAb with LEWVGYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTA
DEC-205 mAb VYYCARWTSGLDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
ScFv AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
VTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP
ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK
VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQL
VESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWV
AVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
YYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGG
GSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR
LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Edrecolomab HC DEC-205 523 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQQSGAELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGLE
WIGVINPGSGGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDSA
VYFCARDGPWFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGS
NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPK
LLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGY
SYPYTFGGGTKLEIK
HC tumor 524 QVQLQQSGAELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGL

Antibody Region SEQ Sequence ID
NO:
mAb with EWIGVINPGSGGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDS
DEC-205 mAb AVYFCARDGPWFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGG
ScFv TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS
VVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Adecatumum HC DEC-205 525 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
ab mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLLESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE
WVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCAKDMGWGSGWRPYYYYGMDVWGQGTTVTVSSGGGGSG
GGGSGGGGSGGGGSELQMTQSPSSLSASVGDRVTITCRTSQSISSYL
NWYQQKPGQPPKWYWASTRESGVPDRFSGSGSGTDFTLTISSLQP
EDSATYYCQQSYDIPYTFGQGTKLEIK
HC tumor 526 EVQLLESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGL
mAb with EWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
DEC-205 mAb TAVYYCAKDMGWGSGWRPYYYYGMDVWGQGTTVTVSSASTKGP
ScFv SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV
DVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL
HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
GGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMY
WVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTL
YLQMNSLRAEDTAVYYCARDLWGWYFDWGQGTLVTVSSGGGG
SGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSS
YLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSL
EPEDFAVYYCQQRRNWPLTFGGGTKVEIK
Anetumab HC DEC-205 527 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VELVQSGAEVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLE
WMGIIDPGDSRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAM

Antibody Region SEQ Sequence ID
NO:
YYCARGQLYGGTYMDGWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSDIALTQPASVSGSPGQSITISCTGTSSDIGGYNSVSWYQQHPGK
APKLMIYGVNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCS
SYDIESATPVFGGGTKLTVL
HC tumor 528 QVELVQSGAEVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLE
mAb with WMGIIDPGDSRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAM
DEC-205 mAb YYCARGQLYGGTYMDGWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
huDS6 HC DEC-205 529 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
AQLVQSGAEVVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGL
EWIGYIYPGNGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDSA
VYFCARGDSVPFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATMSASPGERVTITCSAHSSVSFMHWFQQKPGTSPKLW
IYSTSSLASGVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFP
LTFGAGTKLELK
HC tumor 530 QAQLVQSGAEVVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQG
mAb with LEWIGYIYPGNGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDS
DEC-205 mAb AVYFCARGDS VPFAWGQGTLVTVSAASTKGPSVFPLAPSSKSTSG
ScFv GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Lifastuzumab HC DEC-205 531 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY

Antibody Region SEQ Sequence ID
NO:
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLE
WVATIGRVAFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARHRGFDVGHFDFWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQ
QKPGKAPKLLIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCFQGSFNPLTFGQGTKVEIK
HC tumor 532 EVQLVESGGGLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLE
mAb with WVATIGRVAFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDT
DEC-205 mAb AVYYCARHRGFDVGHFDFWGQGTLVTVSSASTKGPSVFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Sacituzumab HC DEC-205 533 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQQSGSELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGL
KWMGWINTYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADDT
AVYFCARGGFGSSWYFDVWGQGSLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQLTQSPSSLSASVGDRVSITCKASQDVSIAVAWYQQKPG
KAPKLLIYSASYRYTGVPDRFSGSGSGTDFTLTISSLQPEDFAVYYCQ
QHYITPLTFGAGTKVEIK
HC tumor 534 QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQG
mAb with LKWMGWINTYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADD
DEC-205 mAb TAVYFCARGGFGSSYWYFDVWGQGSLVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT
CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
TAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQ
APRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQ
RRNWPLTFGGGTKVEIK

mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED

Antibody Region SEQ Sequence ID
NO:
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VKLQQSGPELKKPGETVKISCKASGYTFTEFGMNWVKQAPGKGLK
WMGWINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDTA
KYFCARWDFYDYVEAMDWGQGTTVTVSSGGGGSGGGGSGGGG
SGGGGSDIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQ
KPGQSPKALIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAE
YFCHQYYTYPLFTFGSGTKLEMK
HC tumor 536 QVKLQQSGPELKKPGETVKISCKASGYTFTEFGMNWVKQAPGKGL
mAb with KWMGWINTKTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDT
DEC-205 mAb AKYFCARWDFYDYVEAMDWGQGTTVTVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT
CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
TAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQ
APRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQ
RRNWPLTFGGGTKVEIK
Humanized HC DEC-205 818 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
PR1A3 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQG
LEWMGWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSD
DTAVYYCARWDFAYYVEAMDYWGQGTTVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWY
QQKPGKAPKWYSASYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCHQYYTYPLFTFGQGTKLEIK
HC tumor 819 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQG
mAb with LEWMGWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSD
DEC-205 mAb DTAVYYCARWDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLA
ScFv PSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK
THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW
LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGS
GGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQ
APGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQM
NSLRAEDTAVYYCARDLWGWYFDYWGQGTLVTVSSGGGGSGGG

Antibody Region SEQ Sequence ID
NO:
GSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAW
YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDF
AVYYCQQRRNWPLTFGGGTKVEIK
Humanized HC DEC-205 836 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
Ab2-3 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLQESGPGLVKPGGSLSLSCAASGFVFSSYDMSWVRQTPERGLEW
VAYISSGGGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAV
YYCAAHYFGSSGPFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSDIQMTQSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSP
KLLVYNTRTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHH
YGTPFTFGSGTKLEIK
HC tumor 837 EVQLQESGPGLVKPGGSLSLSCAASGFVFSSYDMSWVRQTPERGLE
mAb with WVAYISSGGGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTA
DEC-205 mAb VYYCAAHYFGSSGPFAWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
TAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQ
APRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQ
RRNWPLTFGGGTKVEIK
IMAB362, HC DEC-205 537 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
CLAUDIXIM mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
AB tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLQQPGAELVRPGASVKLSCKASGYTFTSWINWVKQRPGQGLE
WIGNIYPSDSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSA
VYYCTRSWRGNSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGG
GSDIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQ
KPGQPPKLLIWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAV
YYCQNDYSYPFTFGSGTKLEIK
HC tumor 538 QVQLQQPGAELVRPGAS VKLSCKASGYTFTSWINWVKQRPGQGL
mAb with EWIGNIYPSDSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSA
DEC-205 mAb VYYCTRSWRGNSFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSG
ScFv GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL

Antibody Region SEQ Sequence ID
NO:
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK

mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKGLE
WVAVIWYDGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDGYDILTGNPRDFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTY
LSWLQQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEA
EDVGVYYCMQSTHVPRTFGQGTKVEIK
HC tumor 540 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKG
mAb with LEWVAVIWYDGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAE
DEC-205 mAb DTAVYYCARDGYDILTGNPRDFDYWGQGTLVTVSSASTKGPSVFPL
ScFv APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD
KTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE
DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW
LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL
YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGS
GGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQ
APGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMN
SLRAEDTAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGS
GGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQ
QKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAV
YYCQQRRNWPLTFGGGTKVEIK

mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLQESGPGLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLE
WMGYISYNGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATY
YCVTASRGFPWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
MTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYH
GTNLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWT
FGGGTKLEIK
HC tumor 542 EVQLQESGPGLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLE
mAb with WMGYISYNGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATY
DEC-205 mAb YCVTASRGFPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

Antibody Region SEQ Sequence ID
NO:
ScFv GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTV
PSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG
VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN
KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVES
GGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVI
WYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
ARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPL
TFGGGTKVEIK
Sibrotuzumab HC DEC-205 543 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKTSRYTFTEYTIHWVRQAPGQRLE
WIGGINPNNGIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTAV
YYCARRRIAYGYDEGHAMDWGQGTLVTVSSGGGGSGGGGSGGG
GSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSRNQKNYL
AWYQQKPGQPPKLLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQA
EDVAVYYCQQYFSYPLTFGQGTKVEIK
HC tumor 544 QVQLVQSGAEVKKPGASVKVSCKTSRYTFTEYTIHWVRQAPGQRL
mAb with EWIGGINPNNGIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTA
DEC-205 mAb VYYCARRRIAYGYDEGHAMDWGQGTLVTVSSASTKGPSVFPLAP
ScFv SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT
HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP
EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN
GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGG
GSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGK
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRA
EDTAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGG
GSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKP
GQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYC
QQRRNWPLTFGGGTKVEIK
DS-8895a HC DEC-205 545 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
variant 1 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLE
WMGWINTYTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDTA
VYYCATYYRYERDFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSDIVMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKP

Antibody Region SEQ Sequence ID
NO:
GQSPQLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYY
CFQGSHVPYTFGQGTKVEIK
HC tumor 546 QVQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQG
mAb with LEWMGWINTYTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDT
DEC-205 mAb AVYYCATYYRYERDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
DS-8895a HC DEC-205 547 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
variant 2 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
IQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLK
WMGWINTYTGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDTA
VYYCATYYRYERDFDYWGQGTLVTVSSGGGGSGGGGSGGGSGGG
GSDVLMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPG
QSPQLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC
FQGSHVPYTFGQGTKVEIK
HC tumor 548 QIQLVQSGAEVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGL
mAb with KWMGWINTYTGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDT
DEC-205 mAb AVYYCATYYRYERDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGGSGGGGSGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK

mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

Antibody Region SEQ Sequence ID
NO:
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLLESGGGLVQPGGSLRLSCAASGFTFSHYMMAWVRQAPGKGLE
WVSRIGPSGGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCAGYDSGYDYVAVAGPAEYFQHWGQGTLVTVSSGGGGSGGG
GSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISTWLAW
YQQKPGKAPKLLIYKASNLHTGVPSRFSGSGSGTEFSLTISGLQPDDF
ATYYCQQYNSYSRTFGQGTKVEIK
HC tumor 550 EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYMMAWVRQAPGKGL
mAb with EWVSRIGPSGGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
DEC-205 mAb AVYYCAGYDSGYDYVAVAGPAEYFQHWGQGTLVTVSSASTKGPS
ScFv VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP
AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPK
SCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH
QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE
EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG
SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGG
GGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYW
VRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYL
QMNSLRAEDTAVYYCARDLWGWYFDYWGQGTLVTVSSGGGGSG
GGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYL
AWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPE
DFAVYYCQQRRNWPLTFGGGTKVEIK
Narnatumab HC DEC-205 551 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLE
WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDT
AVYYCTRDGYSSGRHYGMDVWGQGTTVIVSSGGGGSGGGGSGGG
GSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSRYLAWYQQKP
GQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYC
QQRSNWPRTFGQGTKVEIK
HC tumor 552 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLE
mAb with WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDT
DEC-205 mAb AVYYCTRDGYSSGRHYGMDVWGQGTTVIVSSASTKGPSVFPLAPSS
ScFv KSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT
CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGK
EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVS
LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
TAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQ
APRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQ
RRNWPLTFGGGTKVEIK

mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY

Antibody Region SEQ Sequence ID
NO:
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGPALVKPTQTLTLTCTVSGFSLTGYSVNWIRQPPGKALEW
LGMIWGDGSTDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTAT
YYCARDYYFNYASWFAYWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSDIQMTQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKT
VKLLIYYTSNLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQY
SELPWTFGQGTKVEIK
HC tumor 554 EVQLVESGPALVKPTQTLTLTCTVSGFSLTGYSVNWIRQPPGKALE
mAb with WLGMIWGDGSTDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTA
DEC-205 mAb TYYCARDYYFNYASWFAWGQGTLVTVSSASTKGPS VFPLAPS S KS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Farletuzumab HC DEC-205 555 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPS S KS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLE
WVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTG
VYFCARHGDDPAWFAYWGQGTPVTVSSGGGGSGGGGSGGGGSGG
GGSDIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAP
KPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQW
SSYPYMYTFGQGTKVEIK
HC tumor 556 EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLE
mAb with WVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTG
DEC-205 mAb VYFCARHGDDPAWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTS
ScFv GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
S SVVTVPS S SLGTQTYICNVNHKPSNTKVDKKVEPKS CDKTHTCPPC
PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQV
QLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR

Antibody Region SEQ Sequence ID
NO:
RNWPLTFGGGTKVEIK
Mirvetuximab HC DEC-205 557 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLE
WIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFA
VYYCTRYDGSRAMDWGQGTTVTVSSGGGGSGGGGSGGGGSGGG
GSDIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPG
QQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYC
QQSREYPYTFGGGTKLEIK
HC tumor 558 QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSL
mAb with EWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDF
DEC-205 mAb AVYYCTRYDGSRAMDWGQGTTVTVSSASTKGPSVFPLAPSSKSTS
ScFv GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC
PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQV
QLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
J591 variant 1 HC DEC-205 559 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLQQSGPELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWI
GNINPNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVY
YCAAGWNFDWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSDIV
MTQSHKFMSTSVGDRVSIICKASQDVGTAVDWYQQKPGQSPKLLIY
WASTRHTGVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQYNSYP
LTFGAGTMLDLK
HC tumor 560 EVQLQQSGPELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLE
mAb with WIGNINPNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSA
DEC-205 mAb VYYCAAGWNFDWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTA
ScFv ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV
TVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPE
LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQL

Antibody Region SEQ Sequence ID
NO:
VESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWV
AVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
YYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGG
GSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR
LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
J591 variant 2 HC DEC-205 561 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLQQSGPELVKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWI
GNINPNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVY
YCAAGWNFDWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIV
MTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLI
YGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSY
PYTFGGGTKLEIK
HC tumor 562 EVQLQQSGPELVKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLE
mAb with WIGNINPNNGGTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSA
DEC-205 mAb VYYCAAGWNFDWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTA
ScFv ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV
TVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPE
LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV
SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK
GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQL
VESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWV
AVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
YYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGG
GSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR
LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Rovalpituzum HC DEC-205 563 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
ab mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGL
EWMGWINTYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDD
TAVYYCARIGDSSPSDYWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVMTQSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQA
PRLLIYYASNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQD
YTSPWTFGQGTKLEIK
HC tumor 564 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQG
mAb with LEWMGWINTYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSD
DEC-205 mAb DTAVYYCARIGDSSPSDYWGQGTLVTVSSASTKGPSVFPLAPSSKST
ScFv SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPP

Antibody Region SEQ Sequence ID
NO:
CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK

mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPS S KS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGPEVKKPGAS VKVSCKASGYTFTDYAVHWVRQAPGKRLE
WIGVISTYNDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTA
VYYCARGNSYFYALDYWGQGTSVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKP
GQAPRLLIYRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYC
QQSNEDPWTFGGGTKLEIK
HC tumor 566 QVQLVQSGPEVKKPGASVKVSCKASGYTFTDYAVHWVRQAPGKR
mAb with LEWIGVISTYNDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSED
DEC-205 mAb TAVYYCARGNSYFYALDWGQGTSVTVSSASTKGPS VFPLAPS S KS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Antibody to HC DEC-205 567 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
PTK7 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPS S KS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSSYAFHWVRQAPGKGLE
WVAVISYDGSIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARTYYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIK
YASQSFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPIT
FGQGTRLEIK

Antibody Region SEQ Sequence ID
NO:
HC tumor 568 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAFHWVRQAPGKGL
mAb with EWVAVISYDGSIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
DEC-205 mAb AVYYCARTYYFDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT
ScFv AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
VTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP
ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK
VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV
KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQL
VESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWV
AVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
YYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGG
GSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR
LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Ladiratuzuma HC DEC-205 569 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
b mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQGL
EWMGWIDPENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDD
TAVYYCAVHNAHYGTWFAYWGQGTLVTVSSGGGGSGGGGSGGG
GSGGGGSDVVMTQSPLSLPVTLGQPASISCRSSQSLLHSSGNTYLEY
FQQRPGQSPRPLIYKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDV
GVYYCFQGSHVPYTFGGGTKVEIK
HC tumor 570 QVQLVQSGAEVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQG
mAb with LEWMGWIDPENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSD
DEC-205 mAb DTAVYYCAVHNAHYGTWFAYWGQGTLVTVSSASTKGPSVFPLAPS
ScFv SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT
HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP
EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN
GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK
LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGG
GSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGK
GLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRA
EDTAVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGG
GSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKP
GQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYC
QQRRNWPLTFGGGTKVEIK
Cirmtuzumab HC DEC-205 571 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLY
tumor mAb LQMNSLRAEDTAVYYCARDLWGWYFDWGQGTLVTVSSASTKGP
ScFv SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV
DVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL
HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
GGGGSGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGYAFTAYNIHW

Antibody Region SEQ Sequence ID
NO:
VRQAPGQGLEWMGSFDPYDGGSSYNQKFKDRLTISKDTSKNQVVL
TMTNMDPVDTATYYCARGWYYFDYWGHGTLVTVSSGGGGSGGG
GSGGGGSGGGGSDIVMTQTPLSLPVTPGEPASISCRASKSISKYLAW
YQQKPGQAPRLLIYSGSTLQSGIPPRFSGSGYGTDFTLTINNIESEDA
AYYFCQQHDESPY TFGEGTKVEIK
HC tumor 572 QVQLQESGPGLVKPSQTLSLTCTVSGYAFTAYNIHWVRQAPGQGLE
mAb with WMGSFDPYDGGSSYNQKFKDRLTISKDTSKNQVVLTMTNMDPVDT
DEC-205 mAb ATYYCARGWYYFDYWGHGTLVTVSSASTKGPSVFPLAPSSKSTSG
ScFv GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS
SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Antibody to HC DEC-205 573 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
MAGE-A3 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLY
tumor mAb LQMNSLRAEDTAVYYCARDLWGWYFDWGQGTLVTVSSASTKGP
ScFv SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP
KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV
DVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL
HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD
GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
GGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCTASGFRFRSHGMH
WVRQAPGKGLEWVAVISYDGNNKLYADSVKGRITISRDNSKNTLFL
QMNNVRAEDTAVYYCASPYTSDWQYFQYWGQGTLVIVSSGGGGS
GGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATFSCRASQNISTT
LAWYQQKPGQAPRLLIYDTSTRATGIPARFSGSGSGTEFTLTISSLQS
EDLAVYYCQQSNSWPLTFGGGTKVEIK
HC tumor 574 QVQLVESGGGVVQPGRSLRLSCTASGFRFRSHGMHWVRQAPGKGL
mAb with EWVAVISYDGNNKLYADSVKGRITISRDNSKNTLFLQMNNVRAEDT
DEC-205 mAb AVYYCASPYTSDWQYFQWGQGTLVIVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Antibody to HC DEC-205 575 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
NY-ESO-1 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

Antibody Region SEQ Sequence ID
NO:
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVQSGGGVVRPGGSLRLSCAASGFSFIDYGMSWVRQVPGKGLE
WVAGMNWSGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVEDT
ALYFCARGEYSNRFDPRGRGTLVTVSSGGGGSGGGGSGGGGSGGG
GSDIVMTQTPLSLPVTLGQPASLSCRSSQSLVFTDGNTYLNWFQQRP
GQSPRRLIYKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYC
MQGTHWPPIFGQGTKVEIK
HC tumor 576 QVQLVQSGGGVVRPGGSLRLSCAASGFSFIDYGMSWVRQVPGKGL
mAb with EWVAGMNWSGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVED
DEC-205 mAb TALYFCARGEYSNRFDPRGRGTLVTVSSASTKGPSVFPLAPSSKSTS
ScFv GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC
PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN
WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQV
QLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Trastuzumab HC DEC-205 686 QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSE
VQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLE
WVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDT
AVYYCSRWGGDGFYAMDYWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKP
GKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYC
QQHYTTPPTFGQGTKVEIK
HC tumor 687 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLE
mAb with WVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDT
DEC-205 mAb AVYYCSRWGGDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSK
ScFv STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC
PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK

Antibody Region SEQ Sequence ID
NO:
mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
tumor mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPSVFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
(LH,25mer) SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF
NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY
KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSD
IQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLL
IYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPP
TFGQGTKVEIKGGGGSGGGGSGGGGSGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTN
GYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG
GDGFYAMDWGQGTLVTVSS
TABLE 9. Fusion Sequences ¨ CD40 fusions via the light chain Antibody Region SEQ Sequence ID
NO:
Pertuzumab LC CD40 766 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNP
NSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCAR
NLGPSFYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQM
TQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSA
SYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFG
QGTKVEIK
LC tumor 23 DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKL
mAb LIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIY
containing PYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
CD40 mAb REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQS
GAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGW
INPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Cetuximab LC CD40 703 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLKQSGP
GLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGG
NTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTY
YDYEFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGSDILLTQS
PVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESIS
GIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTK
LELK
LC tumor 36 DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIK
mAb YASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTT
containing FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA
CD40 mAb KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH
ScFv KVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGAE

Antibody Region SEQ Sequence ID
NO:
VKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINP
DSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCAR
DQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGK
APNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ
ANIFPLTFGGGTKVEIK
Panitumumab LC CD40 760 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQESGP
GLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKGLEWIGHIYY
SGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVT
GAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS
SLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLE
TGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTK
VEIK
LC tumor 49 DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKL
mAb LIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLP
containing LAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Nimotuzumab LC CD40 751 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGA
EVKKPGSSVKVSCKASGYTFTNYYIWVRQAPGQGLEWIGGINPTS
GGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAFYFCARQGL
WFDSDGRGFDFWGQGSTVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
MTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPGKAP
KLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQYSH
VPWTFGQGTKLEIK
LC tumor 62 DIQMTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPG
mAb KAPKLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQ
containing YSHVPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
CD40 mAb NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
ScFv ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQL
VQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEW
MGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTA
VYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWY
QQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQANIFPLTFGGGTKVEIK
Zalutumumab LC CD40 802 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVAVIWD
DGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DGITMVRGVMKDYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSAIQLTQSPSSLSASVGDRVTITCRASQDISSALVWYQQKPGKAP

Antibody Region SEQ Sequence ID
NO:
KLLIYDASSLESGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQFNS
YPLTFGGGTKVEIK
LC tumor 75 AIQLTQSPSSLSASVGDRVTITCRASQDISSALVWYQQKPGKAPKLLI
mAb YDASSLESGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQFNSYPL
containing TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
CD40 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWIN
PDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCA
RDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPG
KAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
QANIFPLTFGGGTKVEIK
Onartuzumab LC CD40 757 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGLEWVGMIDPS
NSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDTAVYYCATYR
SYVTPLDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQ
SPSSLSASVGDRVTITCKSSQSLLYTSSQKNYLAWYQQKPGKAPKLL
IWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYAY
PWTFGQGTKVEIK
LC tumor 88 DIQMTQSPSSLSASVGDRVTITCKSSQSLLYTSSQKNYLAWYQQKP
mAb GKAPKLLIYWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
containing QQYYAYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC
CD40 mAb LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
ScFv LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL
EWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDD
TAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSGGGGSGGG
GSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLA
WYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQANIFPLTFGGGTKVEIK
Patritumab LC CD40 763 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQWG
AGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGLEWIGEINHS
GSTNYNPSLKSRVTISVETSKNQFSLKLSSVTAADTAVYYCARDKW
TWYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIEMTQSP
DSLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNPGQPPKLLIY
WASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTP
RTFGQGTKVEIK
LC tumor 101 DIEMTQSPDSLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNP
mAb GQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYY
containing CQQYYSTPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC
CD40 mAb LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
ScFv LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL
EWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDD
TAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSGGGGSGGG
GSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLA
WYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQANIFPLTFGGGTKVEIK
Clivatuzumab LC CD40 709 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP

Antibody Region SEQ Sequence ID
NO:
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGA
EVKKPGASVKVSCEASGYTFPSYVLHWVKQAPGQGLEWIGYINPY
NDGTQYNEKFKGKATLTRDTSINTAYMELSRLRSDDTAVYYCARG
FGGSYGFAWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLT
QSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGKAPKLWIYS
TSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWNRYPYT
FGGGTRLEIK
LC tumor 114 DIQLTQSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGKAPK
mAb LWIYSTSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWN
containing RYPYTFGGGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
CD40 mAb YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
ScFv YEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQ
SGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMG
WINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVY
YCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGG
GGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQ
KPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQANIFPLTFGGGTKVEIK
Sofituzumab LC CD40 790 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLEWVGYISY
SGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWT
SGLDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS
SLSASVGDRVTITCKASDLII-INWLAWYQQKPGKAPKWYGATSLE
TGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTTPFTFGQGT
KVEIK
LC tumor 127 DIQMTQSPSSLSASVGDRVTITCKASDLII-INWLAWYQQKPGKAPKL
mAb LIYGATSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTT
containing PFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Edrecolomab LC CD40 718 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGA
ELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGLEWIGVINPGS
GGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDSAVYFCARDG
PWFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGSNIVMTQSP
KSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYGASN
RYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFG
GGTKLEIK
LC tumor 140 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPK
mAb LLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQG
containing YSYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
CD40 mAb YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
ScFv YEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQ
SGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMG

Antibody Region SEQ Sequence ID
NO:
WINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVY
YCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGG
GGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQ
KPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQANIFPLTFGGGTKVEIK
Adecatumum LC CD40 694 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
ab mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLLESGG
GVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYD
GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKD
MGWGSGWRPYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGS
GGGGSELQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGQ
PPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQPEDSATYYCQQ
SYDIPYTFGQGTKLEIK
LC tumor 153 ELQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGQPPKLLI
mAb WASTRESGVPDRFSGSGSGTDFTLTISSLQPEDSATYYCQQSYDIP
containing YTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
CD40 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWIN
PDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCA
RDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPG
KAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
QANIFPLTFGGGTKVEIK
Anetumab LC CD40 700 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVELVQSGA
EVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLEWMGIIDPGD
SRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARGQL
YGGTYMDGWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIALT
QPASVSGSPGQSITISCTGTSSDIGGYNSVSWYQQHPGKAPKLMIYG
VNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYDIESAT
PVFGGGTKLTVL
LC tumor 166 DIALTQPASVSGSPGQSITISCTGTSSDIGGYNSVSWYQQHPGKAPKL
mAb MIYGVNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYDI
containing ESATPVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLIS
CD40 mAb DFYPGAVTVAWKGDSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE
ScFv QWKSHRSYSCQVTHEGSTVEKTVAPTECSGGGGSGGGGSQVQLVQ
SGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMG
WINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVY
YCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGG
GGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQ
KPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQANIFPLTFGGGTKVEIK
huDS6 LC CD40 724 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQAQLVQSGA
EVVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGYIYPG
NGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDSAVYFCARGD
SVPFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGSEIVLTQSP
ATMSASPGERVTITCSAHSSVSFMHWFQQKPGTSPKLWIYSTSSLAS
GVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFPLTFGAGTK

Antibody Region SEQ Sequence ID
NO:
LELK
LC tumor 179 EIVLTQSPATMSASPGERVTITCSAHSSVSFMHWFQQKPGTSPKLWI
mAb YSTSSLASGVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFP
containing LTFGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Lifastuzumab LC CD40 736 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLEWVATIGRV
AFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARH
RGFDVGHFDFWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
MTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQQKPGKAP
KLLIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQGS
FNPLTFGQGTKVEIK
LC tumor 192 DIQMTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQQKPGK
mAb APKLLIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQ
containing GSFNPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
CD40 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQ
QKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQANIFPLTFGGGTKVEIK
Sacituzumab LC CD40 781 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGS
ELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGLKWMGWIN
TYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYFCARG
GFGSSWYFDVWGQGSLVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
LTQSPSSLSASVGDRVSITCKASQDVSIAVAWYQQKPGKAPKLLIYS
ASYRYTGVPDRFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITPLTF
GAGTKVEIK
LC tumor 205 DIQLTQSPSSLSASVGDRVSITCKASQDVSIAVAWYQQKPGKAPKLL
mAb IYSASYRYTGVPDRFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITP
containing LTFGAGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
CD40 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWIN
PDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCA
RDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPG
KAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
QANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE

Antibody Region SEQ Sequence ID
NO:
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVKLQQSGP
ELKKPGETVKISCKASGYTFTEFGMNWVKQAPGKGLKWMGWINT
KTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDTAKYFCARW
DFYDYVEAMDWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDI
VMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKA
LIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCHQYYT
YPLFTFGSGTKLEMK
LC tumor 218 DIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSP
mAb KALIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCHQY
containing YTYPLFTFGSGTKLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
CD40 mAb NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
ScFv ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQL
VQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEW
MGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTA
VYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWY
QQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQANIFPLTFGGGTKVEIK
Humanized LC CD40 820 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
PR1A3 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWMGWINT
KTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR
WDFAYYVEAMDWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGS
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPK
LLIYSASYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYT
YPLFTFGQGTKLEIK
LC tumor 817 DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPK
mAb LLIYSASYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYT
containing YPLFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
CD40 mAb PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQS
GAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGW
INPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
LC tumor 844 DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPK
mAb LLIYSASYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYT
containing YPLFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
CD40 mab PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
scFv (LH) EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSDIQMTQS
PSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTL
QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGT
KVEIKGGGGSGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVK
VSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQ
KFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTN
GVCSYFDWGQGTLVTVSS
Humanized LC CD40 838 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
Ab2-3 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQESGP
GLVKPGGSLSLSCAASGFVFSSYDMSWVRQTPERGLEWVAYISSGG
GITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCAAHY

Antibody Region SEQ Sequence ID
NO:
FGSSGPFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMT
QSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSPKLLVYNTR
TLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGTPFTFGS
GTKLEIK
LC tumor 835 DIQMTQSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSPKLL
mAb VYNTRTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGT
containing PFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
LC tumor 842 DIQMTQSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSPKLL
mAb VYNTRTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGT
containing PFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mab EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
scFv (LH) KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSDIQMTQSPS
SVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNLLIYTASTLQ
SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFPLTFGGGTK
VEIKGGGGSGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVS
CKASGYTFTGYYMHWVRQAPGQGLEWMGWINPDSGGTNYAQKF
QGRVTMTRDTSISTAYMELNRLRSDDTAVYYCARDQPLGYCTNGV
CSYFDWGQGTLVTVSS
IMAB362, LC CD40 727 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
CLAUDIXIM mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
AB containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQPGA
ELVRPGASVKLSCKASGYTFTSWINWVKQRPGQGLEWIGNIYPSD
SYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRSW
RGNSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQS
PSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLL
IWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYS
YPFTFGSGTKLEIK
LC tumor 231 DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQK
mAb PGQPPKLLIWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVY
containing YCQNDYSYPFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVC
CD40 mAb LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
ScFv LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL
EWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDD
TAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSGGGGSGGG
GSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLA
WYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKGLEWVAVIWY
DGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DGYDILTGNPRDFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGG
GSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRP
GQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC
MQSTHVPRTFGQGTKVEIK

Antibody Region SEQ Sequence ID
NO:
LC tumor 270 DTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPG
mAb QPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC
containing MQSTHVPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL
CD40 mAb LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
ScFv SKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQV
QLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDT
AVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAW
YQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQESGP
GLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWMGYISYN
GNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRG
FPWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSM
SVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGTNLDDGV
PSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTKLE
IK
LC tumor 283 DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGL
mAb IYHGTNLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQF
containing PWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
CD40 mAb REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQS
GAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGW
INPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Sibrotuzumab LC CD40 787 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKTSRYTFTEYTIHWVRQAPGQRLEWIGGINPNN
GIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTAVYYCARRRIA
YGYDEGHAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDI
VMTQSPDSLAVSLGERATINCKSSQSLLYSRNQKNYLAWYQQKPG
QPPKLLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQAEDVAVYYC
QQYFSYPLTFGQGTKVEIK
LC tumor 296 DIVMTQSPDSLAVSLGERATINCKSSQSLLYSRNQKNYLAWYQQKP
mAb GQPPKLLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQAEDVAVYY
containing CQQYFSYPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC
CD40 mAb LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
ScFv LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQ
VQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL
EWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDD
TAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSGGGGSGGG
GSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLA
WYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPED
FATYYCQQANIFPLTFGGGTKVEIK
DS-8895a LC CD40 712 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
variant 1 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK

Antibody Region SEQ Sequence ID
NO:
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLEWMGWINT
YTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDTAVYYCATYY
RYERDFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMT
QSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSPQLLIY
KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVP
YTFGQGTKVEIK
LC tumor 309 DIVMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSP
mAb QLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQG
containing SHVPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
CD40 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQ
QKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQANIFPLTFGGGTKVEIK
DS-8895a LC CD40 715 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
variant 2 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQIQLVQSGA
EVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLKWMGWINT
YTGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDTAVYYCATYY
RYERDFDWGQGTLVTVSSGGGGSGGGGSGGGSGGGGSDVLMTQ
SPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSPQLLIYK
VSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYT
FGQGTKVEIK
LC tumor 322 DVLMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQS
mAb PQLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQ
containing GSHVPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
CD40 mAb NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
ScFv ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQL
VQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEW
MGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTA
VYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWY
QQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLLESGG
GLVQPGGSLRLSCAASGFTFSHYMMAWVRQAPGKGLEWVSRIGPS
GGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGY
DSGYDYVAVAGPAEYFQHWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPG
KAPKLLIYKASNLHTGVPSRFSGSGSGTEFSLTISGLQPDDFATYYCQ
QYNSYSRTFGQGTKVEIK
LC tumor 335 DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLL
mAb IYKASNLHTGVPSRFSGSGSGTEFSLTISGLQPDDFATYYCQQYNSY
containing SRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG

Antibody Region SEQ Sequence ID
NO:
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Narnatumab LC CD40 748 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLEWVANIKQD
GSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDTAVYYCTRD
GYSSGRHYGMDVWGQGTTVIVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSRYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPR
TFGQGTKVEIK
LC tumor 348 EIVLTQSPATLSLSPGERATLSCRASQSVSRYLAWYQQKPGQAPRLL
mAb IYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWP
containing RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGP
ALVKPTQTLTLTCTVSGFSLTGYSVNWIRQPPGKALEWLGMIWGD
GSTDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARDY
YFNYASWFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
MTQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKTVKLLIYY
TSNLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYSELPWT
FGQGTKVEIK
LC tumor 361 DIQMTQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKTVKLL
mAb IYYTSNLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYSELP
containing WTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK
Farletuzumab LC CD40 721 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSG
GSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARH
GDDPAWFAWGQGTPVTVSSGGGGSGGGGSGGGGSGGGGSDIQL
TQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYG
TSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYM
YTFGQGTKVEIK
LC tumor 374 DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKP

Antibody Region SEQ Sequence ID
NO:
mAb WIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSS
containing YPYMYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
CD40 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQ
QKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQANIFPLTFGGGTKVEIK
Mirvetuximab LC CD40 745 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYD
GDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYD
GSRAMDYWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDIVLTQ
SPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIY
RASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPY
TFGGGTKLEIK
LC tumor 387 DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQ
mAb PRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQ
containing SREYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
CD40 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQ
QKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQANIFPLTFGGGTKVEIK
J591 variant 1 LC CD40 730 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQQSGP
ELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNINPNNG
GTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWN
FDWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSHKF
MSTSVGDRVSIICKASQDVGTAVDWYQQKPGQSPKLLIWASTRHT
GVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQYNSYPLTFGAGT
MLDLK
LC tumor 400 DIVMTQSHKFMSTSVGDRVSIICKASQDVGTAVDWYQQKPGQSPK
mAb LLIWASTRHTGVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQY
containing NSYPLTFGAGTMLDLKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
CD40 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQ
QKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQANIFPLTFGGGTKVEIK
J591 variant 2 LC CD40 733 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQQSGP

Antibody Region SEQ Sequence ID
NO:
ELVKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNINPNNG
GTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWN
FDWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVMTQSPKSM
SMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGGT
KLEIK
LC tumor 413 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPK
mAb LLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQG
containing YSYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF
CD40 mAb YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD
ScFv YEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQ
SGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMG
WINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVY
YCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGG
GGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQ
KPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATY
YCQQANIFPLTFGGGTKVEIK
Rovalpituzum LC CD40 778 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
ab mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWIN
TYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCA
RIGDSSPSDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVM
TQSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQAPRLLIYY
ASNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTSPWTF
GQGTKLEIK
LC tumor 426 EIVMTQSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQAPRL
mAb LIYYASNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTS
containing PWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
CD40 mAb REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQS
GAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGW
INPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGP
EVKKPGASVKVSCKASGYTFTDYAVHWVRQAPGKRLEWIGVISTY
NDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTAVYYCAR
GNSYFYALDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKPGQAPRL
LIYRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSNEDP
WTFGGGTKLEIK
LC tumor 439 EIVLTQSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKPGQ
mAb APRLLIYRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQS
containing NEDPWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
CD40 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
QSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWM
GWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAV
YYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSG
GGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQ

Antibody Region SEQ Sequence ID
NO:
QKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAT
YYCQQANIFPLTFGGGTKVEIK
Antibody to LC CD40 688 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
PTK7 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSSYAFHWVRQAPGKGLEWVAVISYD
GSIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARTY
YFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPDF
QSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSG
VPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPITFGQGTRLE
IK
LC tumor 452 EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLI
mAb KYASQSFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPI
containing TFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA
CD40 mAb KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH
ScFv KVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGAE
VKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINP
DSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCAR
DQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGK
APNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ
ANIFPLTFGGGTKVEIK
Ladiratuzuma LC CD40 784 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
b mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQGLEWMGWIDP
ENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYCAV
HNAHYGTWFAWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSD
VVMTQSPLSLPVTLGQPASISCRSSQSLLHSSGNTYLEYFQQRPGQSP
RPLIYKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGS
HVPYTFGGGTKVEIK
LC tumor 465 DVVMTQSPLSLPVTLGQPASISCRSSQSLLHSSGNTYLEYFQQRPGQ
mAb SPRPLIYKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQ
containing GSHVPYTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
CD40 mAb NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
ScFv ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQL
VQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEW
MGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTA
VYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGS
GGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWY
QQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA
TYYCQQANIFPLTFGGGTKVEIK
Cirmtuzumab LC CD40 706 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQESGP
GLVKPSQTLSLTCTVSGYAFTAYNIHWVRQAPGQGLEWMGSFDPY
DGGSSYNQKFKDRLTISKDTSKNQVVLTMTNMDPVDTATYYCARG
WYYFDWGHGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQT
PLSLPVTPGEPASISCRASKSISKYLAWYQQKPGQAPRLLIYSGSTLQ
SGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPY
LC tumor 478 DIVMTQTPLSLPVTPGEPASISCRASKSISKYLAWYQQKPGQAPRLLI
mAb YSGSTLQSGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPY
containing TFGEGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA

Antibody Region SEQ Sequence ID
NO:
CD40 mAb KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH
ScFv KVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGAE
VKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINP
DSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCAR
DQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGK
APNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ
ANIFPLTFGGGTKVEIK
Antibody to LC CD40 739 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
MAGE-A3 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCTASGFRFRSHGMHWVRQAPGKGLEWVAVISYD
GNNKLYADSVKGRITISRDNSKNTLFLQMNNVRAEDTAVYYCASP
YTSDWQYFQWGQGTLVIVSSGGGGSGGGGSGGGGSGGGGSEIV
MTQSPATLSVSPGERATFSCRASQNISTTLAWYQQKPGQAPRLLIYD
TSTRATGIPARFSGSGSGTEFTLTISSLQSEDLAVYYCQQSNSWPLTF
GGGTKVEIK
LC tumor 491 EIVMTQSPATLSVSPGERATFSCRASQNISTTLAWYQQKPGQAPRLL
mAb IYDTSTRATGIPARFSGSGSGTEFTLTISSLQSEDLAVYYCQQSNSWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
CD40 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWIN
PDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYCA
RDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPG
KAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
QANIFPLTFGGGTKVEIK
Antibody to LC CD40 754 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
NY-ESO-1 mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGG
GVVRPGGSLRLSCAASGFSFIDYGMSWVRQVPGKGLEWVAGMNW
SGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVEDTALYFCARG
EYSNRFDPRGRGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQ
TPLSLPVTLGQPASLSCRSSQSLVFTDGNTYLNWFQQRPGQSPRRLI
YKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYCMQGTHW
PPIFGQGTKVEIK
LC tumor 504 DIVMTQTPLSLPVTLGQPASLSCRSSQSLVFTDGNTYLNWFQQRPG
mAb QSPRRLIYKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYC
containing MQGTHWPPIFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL
CD40 mAb LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
ScFv SKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQV
QLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDT
AVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAW
YQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQANIFPLTFGGGTKVEIK
Trastuzumab LC CD40 793 DIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKPGKAPNL
mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTN
GYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

Antibody Region SEQ Sequence ID
NO:
GDGFYAMDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQM
TQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYS
ASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTF
GQGTKVEIK
LC tumor 685 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKL
mAb LIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTT
containing PPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
scFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSDIQMTQSPSS
(LH,25mer) LSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYS
GVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTK
VEIKGGGGSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGG
SLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYAD
SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAM
DWGQGTLVTVSS
TABLE 10. Fusion Sequences ¨ DEC-205 fusions via the light chain Antibody Region SEQ Sequence ID
NO:
Pertuzumab LC DEC-205 767 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNP
NSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCAR
NLGPSFYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQM
TQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSA
SYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFG
QGTKVEIK
LC tumor 768 DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKL
mAb LIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIY
containing PYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
DEC-205 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Cetuximab LC DEC-205 704 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLKQSGP

Antibody Region SEQ Sequence ID
NO:
GLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGG
NTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTY
YDYEFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGSDILLTQS
PVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESIS
GIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTK
LELK
LC tumor 705 DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIK
mAb YASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTF
containing GAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK
DEC-205 mAb VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK
ScFv VYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGGGV
VQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWYDG
SNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDL
WGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQ
SPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASN
RATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFGG
GTKVEIK
Panitumumab LC DEC-205 761 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQESGP
GLVKPSETLSLTCTVSGGSVSSGDYWTWIRQSPGKGLEWIGHIYYS
GNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTG
AFDIWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSS
LSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLET
GVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKV
EIK
LC tumor 762 DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKL
mAb LIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLP
containing LAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
DEC-205 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Nimotuzumab LC DEC-205 752 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGA
EVKKPGSSVKVSCKASGYTFTNYYIWVRQAPGQGLEWIGGINPTS
GGSNFNEKFKTRVTITVDESTNTAYMELSSLRSEDTAFYFCARQGL
WFDSDGRGFDFWGQGSTVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
MTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPGKAP
KLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQYSH
VPWTFGQGTKLEIK
LC tumor 753 DIQMTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPGK
mAb APKLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQY
containing SHVPWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL

Antibody Region SEQ Sequence ID
NO:
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Zalutumumab LC DEC-205 803 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVAVIWD
DGSYKYYGDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DGITMVRGVMKDYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSAIQLTQSPSSLSASVGDRVTITCRASQDISSALVWYQQKPGKAP
KLLIYDASSLESGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQFNS
YPLTFGGGTKVEIK
LC tumor 804 AIQLTQSPSSLSASVGDRVTITCRASQDISSALVWYQQKPGKAPKLLI
mAb YDASSLESGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQFNSYPL
containing TFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK
Onartuzumab LC DEC-205 758 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGYTFTSWLHWVRQAPGKGLEWVGMIDPS
NSDTRFNPNFKDRFTISADTSKNTAYLQMNSLRAEDTAVYYCATYR
SYVTPLDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQ
SPSSLSASVGDRVTITCKSSQSLLYTSSQKNYLAWYQQKPGKAPKLL
IWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYAY
PWTFGQGTKVEIK
LC tumor 759 DIQMTQSPSSLSASVGDRVTITCKSSQSLLYTSSQKNYLAWYQQKPG
mAb KAPKLLIYWASTRESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ
containing QYYAYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL
DEC-205 mAb NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS
ScFv KADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Patritumab LC DEC-205 764 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQWG
AGLLKPSETLSLTCAVYGGSFSGYWSWIRQPPGKGLEWIGEINHSG
STNYNPSLKSRVTISVETSKNQFSLKLSSVTAADTAVYYCARDKWT
WYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIEMTQSPD
SLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNPGQPPKLLIY
WASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPR
TFGQGTKVEIK
LC tumor 765 DIEMTQSPDSLAVSLGERATINCRSSQSVLYSSSNRNYLAWYQQNP
mAb GQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYY

Antibody Region SEQ Sequence ID
NO:
containing CQQYYSTPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC
DEC-205 mAb LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
ScFv LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQ
VQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
Clivatuzumab LC DEC-205 710 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGA
EVKKPGASVKVSCEASGYTFPSYVLHWVKQAPGQGLEWIGYINPY
NDGTQYNEKFKGKATLTRDTSINTAYMELSRLRSDDTAVYYCARG
FGGSYGFAWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLT
QSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGKAPKLWIYS
TSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWNRYPYT
FGGGTRLEIK
LC tumor 711 DIQLTQSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGKAPKL
mAb WIYSTSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWNR
containing YPYTFGGGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
DEC-205 mAb REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Sofituzumab LC DEC-205 791 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLEWVGYISY
SGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWT
SGLDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPS
SLSASVGDRVTITCKASDLIHNWLAWYQQKPGKAPKLLIYGATSLE
TGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTTPFTFGQGT
KVEIK
LC tumor 792 DIQMTQSPSSLSASVGDRVTITCKASDLIHNWLAWYQQKPGKAPKL
mAb LIYGATSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWTT
containing PFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
DEC-205 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Edrecolomab LC DEC-205 719 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGA
ELVRPGTSVKVSCKASGYAFTNYLIEWVKQRPGQGLEWIGVINPGS

Antibody Region SEQ Sequence ID
NO:
GGTNYNEKFKGKATLTADKSSSTAYMQLSSLTSDDSAVYFCARDG
PWFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGSNIVMTQSP
KSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYGASN
RYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFG
GGTKLEIK
LC tumor 720 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPK
mAb LLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGY
containing SYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
DEC-205 mAb PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVES
GGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVI
WYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
ARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPL
TFGGGTKVEIK
Adecatumum LC DEC-205 695 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
ab mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLLESGG
GVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYD
GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKD
MGWGSGWRPYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGS
GGGGSELQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGQ
PPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQPEDSATYYCQQ
SYDIPYTFGQGTKLEIK
LC tumor 696 ELQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGQPPKLLI
mAb WASTRESGVPDRFSGSGSGTDFTLTISSLQPEDSATYYCQQSYDIP
containing YTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK
Anetumab LC DEC-205 701 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVELVQSGA
EVKKPGESLKISCKGSGYSFTSWIGWVRQAPGKGLEWMGIIDPGD
SRTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARGQL
YGGTYMDGWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIALT
QPASVSGSPGQSITISCTGTSSDIGGYNSVSWYQQHPGKAPKLMIYG
VNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYDIESAT
PVFGGGTKLTVL
LC tumor 702 DIALTQPASVSGSPGQSITISCTGTSSDIGGYNSVSWYQQHPGKAPKL
mAb MIYGVNNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYDI
containing ESATPVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLIS
DEC-205 mAb DFYPGAVTVAWKGDSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE
ScFv QWKSHRSYSCQVTHEGSTVEKTVAPTECSGGGGSGGGGSQVQLVE
SGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEWVAVI
WYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
ARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPL

Antibody Region SEQ Sequence ID
NO:
TFGGGTKVEIK
huDS6 LC DEC-205 725 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQAQLVQSGA
EVVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGYIYPG
NGATNYNQKFQGKATLTADPSSSTAYMQISSLTSEDSAVYFCARGD
SVPFAWGQGTLVTVSAGGGGSGGGGSGGGGSGGGGSEIVLTQSP
ATMSASPGERVTITCSAHSSVSFMHWFQQKPGTSPKLWIYSTSSLAS
GVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFPLTFGAGTK
LELK
LC tumor 726 EIVLTQSPATMSASPGERVTITCSAHSSVSFMHWFQQKPGTSPKLWI
mAb YSTSSLASGVPARFGGSGSGTSYSLTISSMEAEDAATYYCQQRSSFP
containing LTFGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
DEC-205 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Lifastuzumab LC DEC-205 737 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFSFSDFAMSWVRQAPGKGLEWVATIGRV
AFHTYYPDSMKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARH
RGFDVGHFDFWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
MTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQQKPGKAP
KLLIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQGSF
NPLTFGQGTKVEIK
LC tumor 738 DIQMTQSPSSLSASVGDRVTITCRSSETLVHSSGNTYLEWYQQKPGK
mAb APKLLIYRVSNRFSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCFQ
containing GSFNPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Sacituzumab LC DEC-205 782 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQSGS
ELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGLKWMGWIN
TYTGEPTYTDDFKGRFAFSLDTSVSTAYLQISSLKADDTAVYFCARG
GFGSSWYFDVWGQGSLVTVSSGGGGSGGGGSGGGGSGGGGSDIQ
LTQSPSSLSASVGDRVSITCKASQDVSIAVAWYQQKPGKAPKLLIYS
ASYRYTGVPDRFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITPLTF
GAGTKVEIK
LC tumor 783 DIQLTQSPSSLSASVGDRVSITCKASQDVSIAVAWYQQKPGKAPKLL
mAb IYSASYRYTGVPDRFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITP
containing LTFGAGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE

Antibody Region SEQ Sequence ID
NO:
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK

mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVKLQQSGP
ELKKPGETVKISCKASGYTFTEFGMNWVKQAPGKGLKWMGWINT
KTGEATYVEEFKGRFAFSLETSATTAYLQINNLKNEDTAKYFCARW
DFYDYVEAMDWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDI
VMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKA
LIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCHQYYT
YPLFTFGSGTKLEMK
LC tumor 774 DIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPK
mAb ALIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCHQYY
containing TYPLFTFGSGTKLEMKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Humanized LC DEC-205 821 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLL
PR1A3 mAb IYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNW
containing PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
tumor mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWMGWIN
TKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR
WDFAYYVEAMDWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGS
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPK
LLIYSASYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYT
YPLFTFGQGTKLEIK
LC tumor 822 DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPK
mAb LLIYSASYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYT
containing YPLFTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
DEC-205 mAb PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVES
GGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVI
WYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
ARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPL
TFGGGTKVEIK
Humanized LC DEC-205 839 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLL
Ab2-3 mAb IYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNW
containing PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
tumor mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQESG
PGLVKPGGSLSLSCAASGFVFSSYDMSWVRQTPERGLEWVAYISSG
GGITYAPSTVKGRFTVSRDNAKNTLYLQMNSLTSEDTAVYYCAAH

Antibody Region SEQ Sequence ID
NO:
YFGSSGPFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQM
TQSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSPKLLVYNT
RTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGTPFTFG
SGTKLEIK
LC tumor 840 DIQMTQSPASLSASVGDRVTITCRASENIFSYLAWYQQKPGKSPKLL
mAb VYNTRTLAEGVPSRFSGSGSGTDFSLTISSLQPEDFATYYCQHHYGT
containing PFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
DEC-205 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLT
FGGGTKVEIK
IMAB362, LC DEC-205 728 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
CLAUDIXIM mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
AB containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQQPGA
ELVRPGASVKLSCKASGYTFTSWINWVKQRPGQGLEWIGNIYPSD
SYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRSW
RGNSFDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQS
PSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLL
IWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSY
PFTFGSGTKLEIK
LC tumor 729 DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKP
mAb GQPPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYY
containing CQNDYSYPFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL
DEC-205 mAb LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
ScFv SKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQV
QLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK

mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKGLEWVAVIWY
DGSDKYYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DGYDILTGNPRDFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPG
QPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCM
QSTHVPRTFGQGTKVEIK
LC tumor 699 DTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPG
mAb QPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCM
containing QSTHVPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL
DEC-205 mAb NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS
ScFv KADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK

Antibody Region SEQ Sequence ID
NO:

EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQESGP
GLVKPSQTLSLTCTVSGYSISRDFAWNWIRQPPGKGLEWMGYISYN
GNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRG
FPWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSM
SVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGTNLDDGV
PSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTKLE
IK
LC tumor 693 DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGL
mAb IYHGTNLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQF
containing PWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
DEC-205 mAb REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Sibrotuzumab LC DEC-205 788 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKTSRYTFTEYTIHWVRQAPGQRLEWIGGINPNN
GIPNYNQKFKGRVTITVDTSASTAYMELSSLRSEDTAVYYCARRRIA
YGYDEGHAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDI
VMTQSPDSLAVSLGERATINCKSSQSLLYSRNQKNYLAWYQQKPG
QPPKLLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQAEDVAVYYC
QQYFSYPLTFGQGTKVEIK
LC tumor 789 DIVMTQSPDSLAVSLGERATINCKSSQSLLYSRNQKNYLAWYQQKP
mAb GQPPKLLIFWASTRESGVPDRFSGSGFGTDFTLTISSLQAEDVAVYY
containing CQQYFSYPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL
DEC-205 mAb LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
ScFv SKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQV
QLVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLE
WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT
AVYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSG
GGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQA
PRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQR
RNWPLTFGGGTKVEIK
DS-8895a LC DEC-205 713 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
variant 1 mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLEWMGWINT
YTGEPTYSDDFKGRVTITADTSTSTAYLELSSLRSEDTAVYYCATYY
RYERDFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMT
QSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSPQLLIY
KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVP
YTFGQGTKVEIK
LC tumor 714 DIVMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQSP
mAb QLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQG
containing SHVPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA

Antibody Region SEQ Sequence ID
NO:
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
DS-8895a LC DEC-205 716 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
variant 2 mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQIQLVQSGAE
VKKPGASVKVSCKASGYTFIDYSMHWVRQAPGQGLKWMGWINTY
TGEPTYSDDFKGRFAFSLDTSTSTAYLELSSLRSEDTAVYYCATYYR
YERDFDWGQGTLVTVSSGGGGSGGGGSGGGSGGGGSDVLMTQS
PLSLPVTPGEPASISCRSSQSIVHS SGITYLEWYLQKPGQSPQLLIYKV
SNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTF
GQGTKVEIK
LC tumor 717 DVLMTQSPLSLPVTPGEPASISCRSSQSIVHSSGITYLEWYLQKPGQS
mAb PQLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQ
containing GSHVPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
DEC-205 mAb NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
ScFv ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQL
VESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWV
AVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
YYCARDLWGWYFDWGQGTLVTVSSGGGGGSGGGGSGGGSGGG
GSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR
LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK

EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLLESGG
GLVQPGGSLRLSCAASGFTFSHYMMAWVRQAPGKGLEWVSRIGPS
GGPTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGY
DSGYDYVAVAGPAEYFQHWGQGTLVTVSSGGGGSGGGGSGGGGS
GGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPG
KAPKLLIYKASNLHTGVPSRFSGSGSGTEFSLTISGLQPDDFATYYCQ
QYNSYSRTFGQGTKVEIK
LC tumor 744 DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLL
mAb IYKASNLHTGVPSRFSGSGSGTEFSLTISGLQPDDFATYYCQQYNSYS
containing RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK
Narnatumab LC DEC-205 749 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFTFSSYLMTWVRQAPGKGLEWVANIKQD
GSEKYYVDSVKGRFTISRDNAKNSLNLQMNSLRAEDTAVYYCTRD
GYSSGRHYGMDVWGQGTTVIVSSGGGGSGGGGSGGGGSGGGGSEI

Antibody Region SEQ Sequence ID
NO:
VLTQSPATLSLSPGERATLSCRASQSVSRYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPR
TFGQGTKVEIK
LC tumor 750 EIVLTQSPATLSLSPGERATLSCRASQSVSRYLAWYQQKPGQAPRLL
mAb IYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWP
containing RTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK

mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGP
ALVKPTQTLTLTCTVSGFSLTGYSVNWIRQPPGKALEWLGMIWGDG
STDYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARDYY
FNYASWFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQM
TQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKTVKLLIYYT
SNLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYSELPWTF
GQGTKVEIK
LC tumor 777 DIQMTQSPSSLSASVGDRVTITCSASQGISNYLNWYQQKPGKTVKLL
mAb IYYTSNLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYSELP
containing WTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
DEC-205 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK
Farletuzumab LC DEC-205 722 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGG
SYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHG
DDPAWFAWGQGTPVTVSSGGGGSGGGGSGGGGSGGGGSDIQLT
QSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGT
SNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMY
TFGQGTKVEIK
LC tumor 723 DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKP
mAb WIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSS
containing YPYMYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Mirvetuximab LC DEC-205 746 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI

Antibody Region SEQ Sequence ID
NO:
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYD
GDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYD
GSRAMDYWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDIVLTQS
PLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYR
ASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYT
FGGGTKLEIK
LC tumor 747 DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQ
mAb PRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQ
containing SREYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
J591 variantl LC DEC-205 731 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQQSGP
ELKKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNINPNNG
GTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWN
FDWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSHKF
MSTSVGDRVSIICKASQDVGTAVDWYQQKPGQSPKLLIWASTRHT
GVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQYNSYPLTFGAGT
MLDLK
LC tumor 732 DIVMTQSHKFMSTSVGDRVSIICKASQDVGTAVDWYQQKPGQSPKL
mAb LIWASTRHTGVPDRFTGSGSGTDFTLTITNVQSEDLADYFCQQYNS
containing YPLTFGAGTMLDLKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
DEC-205 mAb PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVES
GGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVI
WYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
ARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPL
TFGGGTKVEIK
J591 variant 2 LC DEC-205 734 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLQQSGP
ELVKPGTSVRISCKTSGYTFTEYTIHWVKQSHGKSLEWIGNINPNNG
GTTYNQKFEDKATLTVDKSSSTAYMELRSLTSEDSAVYYCAAGWN
FDWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSNIVMTQSPKSM
SMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYT
GVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGGT
KLEIK
LC tumor 735 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPK
mAb LLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQGY
containing SYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY
DEC-205 mAb PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY
ScFv EKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVES

Antibody Region SEQ Sequence ID
NO:
GGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVI
WYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC
ARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI
VLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY
DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPL
TFGGGTKVEIK
Rovalpituzum LC DEC-205 779 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
ab mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWMGWIN
TYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCA
RIGDSSPSDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVMT
QSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQAPRLLIYYA
SNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTSPWTFG
QGTKLEIK
LC tumor 780 EIVMTQSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQAPRL
mAb LIYYASNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTS
containing PWTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP
DEC-205 mAb REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
ScFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESG
GGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIW
YDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA
RDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIV
LTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYD
ASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK

mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGP
EVKKPGASVKVSCKASGYTFTDYAVHWVRQAPGKRLEWIGVISTY
NDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTAVYYCARG
NSYFYALDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSEIVLT
QSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKPGQAPRLLI
YRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSNEDPW
TFGGGTKLEIK
LC tumor 771 EIVLTQSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKPGQ
mAb APRLLIYRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQS
containing NEDPWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN
DEC-205 mAb FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA
ScFv DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLV
ESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVA
VIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY
YCARDLWGWYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGG
SEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRL
LIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Antibody to LC DEC-205 689 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
PTK7 mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSSYAFHWVRQAPGKGLEWVAVISYD
GSIKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARTY
YFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPDF
QSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQSFSG

Antibody Region SEQ Sequence ID
NO:
VPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQS SSLPITFGQGTRLEI
K
LC tumor 690 EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLI
mAb KYASQSFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPI
containing TFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA
DEC-205 mAb KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH
ScFv KVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGGG
VVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWYD
GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARD
LWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLT
QSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK
Ladiratuzuma LC DEC-205 785 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
b mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGA
EVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQGLEWMGWIDP
ENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYCAV
HNAHYGTWFAWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSD
VVMTQSPLSLPVTLGQPASISCRSSQSLLHSSGNTYLEYFQQRPGQSP
RPLIYKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGS
HVPYTFGGGTKVEIK
LC tumor 786 DVVMTQSPLSLPVTLGQPASISCRSSQSLLHSSGNTYLEYFQQRPGQ
mAb SPRPLIYKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQ
containing GSHVPYTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN
DEC-205 mAb NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK
ScFv ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQL
VESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWV
AVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV
YYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGG
GSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPR
LLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRN
WPLTFGGGTKVEIK
Cirmtuzumab LC DEC-205 707 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLQESGP
GLVKPSQTLSLTCTVSGYAFTAYNIHWVRQAPGQGLEWMGSFDPY
DGGSSYNQKFKDRLTISKDTSKNQVVLTMTNMDPVDTATYYCARG
WYYFDWGHGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQT
PLSLPVTPGEPASISCRASKSISKYLAWYQQKPGQAPRLLIYSGSTLQ
SGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPY
LC tumor 708 DIVMTQTPLSLPVTPGEPASISCRASKSISKYLAWYQQKPGQAPRLLI
mAb YSGSTLQSGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCQQHDESPY
containing TFGEGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA
DEC-205 mAb KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH
ScFv KVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGGG
VVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWYD
GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARD
LWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLT
QSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK
Antibody to LC DEC-205 740 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
MAGE-A3 mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE

Antibody Region SEQ Sequence ID
NO:
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCTASGFRFRSHGMHWVRQAPGKGLEWVAVISYD
GNNKLYADSVKGRITISRDNSKNTLFLQMNNVRAEDTAVYYCASP
YTSDWQYFQWGQGTLVIVSSGGGGSGGGGSGGGGSGGGGSEIVM
TQSPATLSVSPGERATFSCRASQNISTTLAWYQQKPGQAPRLLIYDT
STRATGIPARFSGSGSGTEFTLTISSLQSEDLAVYYCQQSNSWPLTFG
GGTKVEIK
LC tumor 741 EIVMTQSPATLSVSPGERATFSCRASQNISTTLAWYQQKPGQAPRLL
mAb IYDTSTRATGIPARFSGSGSGTEFTLTISSLQSEDLAVYYCQQSNSWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK
Antibody to LC DEC-205 755 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
NY-ESO-1 mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSGG
GVVRPGGSLRLSCAASGFSFIDYGMSWVRQVPGKGLEWVAGMNW
SGDKKGHAESVKGRFIISRDNAKNTLYLEMSSLRVEDTALYFCARG
EYSNRFDPRGRGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQ
TPLSLPVTLGQPASLSCRSSQSLVFTDGNTYLNWFQQRPGQSPRRLI
YKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYCMQGTHW
PPIFGQGTKVEIK
LC tumor 756 DIVMTQTPLSLPVTLGQPASLSCRSSQSLVFTDGNTYLNWFQQRPGQ
mAb SPRRLIYKVSSRDPGVPDRFSGTGSGTDFTLEISRVEAEDIGVYYCM
containing QGTHWPPIFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL
DEC-205 mAb NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS
ScFv KADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQ
LVESGGGVVQPGRSLRLSCAASGFTFSNYGMYWVRQAPGKGLEW
VAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA
VYYCARDLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGG
GGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP
RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRR
NWPLTFGGGTKVEIK
Trastuzumab LC DEC-205 794 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI
mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVESGG
GLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTN
GYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG
GDGFYAMDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQM
TQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYS
ASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTF
GQGTKVEIK
LC tumor 795 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKL
mAb LIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTP
containing PTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC-205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
ScFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR

Antibody Region SEQ Sequence ID
NO:
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFG
GGTKVEIK

mAb YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
tumor mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
scFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSDIQMTQSPSS
(LH,25mer) LSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYS
GVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV
EIKGGGGSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGS
LRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADS
VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAM
DWGQGTLVTVSS
TABLE 11. Fusion Sequences ¨ CD40 fusion with DEC205 Antibody Region SEQ Sequence ID
NO:

QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGL
variant 1 mAb with EWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED
CD40 mAb TAVYYCARDLWGWYFDWGQGTLVTVSSASTKGPS VFPLAPSSKS
ScFv TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK
FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE
YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQG
LEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSD
DTAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWL
AWYQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPE
DFATYYCQQANIFPLTFGGGTKVEIK

mAb with LEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSD
DEC205 mAb DTAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSASTKGPSV
ScFv FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKS
CDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ
DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGG
GGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMWV
RQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQ
MNSLRAEDTAVYYCARDLWGWYFDYWGQGTLVTVSSGGGGSGG
GGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLA
WYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPED
FAVYYCQQRRNWPLTFGGGTKVEIK

mAb IYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNW
containing PLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
scFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI

Antibody Region SEQ Sequence ID
NO:
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
scFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVESGG
GVVQPGRSLRLSCAASGFTFSNYGMWVRQAPGKGLEWVAVIWY
DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
DLWGWYFDWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVL
TQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDA
SNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF
GGGTKVEIK

variant 2 mAb with EWMGIIYPGDSDTIYSPSFQGQVTISADKSISTAYLQWSSLKASDTA
CD40 mAb MYYCTRGDRGVDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGG
ScFv TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS
VVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW
YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC
KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL
VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQV
QLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLE
WMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDT
AVYYCARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGG
SGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAW
YQQKPGKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDF
ATYYCQQANIFPLTFGGGTKVEIK

mAb with LEWMGWINPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSD
DEC205 mAb DTAVYYCARDQPLGYCTNGVCSYFDYWGQGTLVTVSSASTKGPSV
ScFv FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKS
CDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV
SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ
DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGG
GGSGGGGSEVQLVQSGAEVKKPGESLRISCKGSGDSFTTWIGWVR
QMPGKGLEWMGIIYPGDSDTIYSPSFQGQVTISADKSISTAYLQWSS
LKASDTAMYYCTRGDRGVDWGQGTLVTVSSGGGGSGGGGSGGG
GSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGISRWLAWYQQK
PEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTISGLQPEDFATYY
CQQYNSYPRTFGQGTKVEIK

mAb LIYAASSLQSGVPSRFSGSGSGTDFTLTISGLQPEDFATYYCQQYNSY
containing PRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
CD40 mAb EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE
scFv KHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVQLVQSG
AEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWI
NPDSGGTNYAQKFQGRVTMTRDTSISTAYMELNRLRSDDTAVYYC
ARDQPLGYCTNGVCSYFDWGQGTLVTVSSGGGGSGGGGSGGGG
SGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGIYSWLAWYQQKP
GKAPNLLIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC
QQANIFPLTFGGGTKVEIK

Antibody Region SEQ Sequence ID
NO:

mAb LIYTASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANIFP
containing LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE
DEC205 mAb AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK
scFv HKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVQSGA
EVKKPGESLRISCKGSGDSFTTYWIGWVRQMPGKGLEWMGIIYPGD
SDTIYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCTRGDRG
VDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSL
SASVGDRVTITCRASQGISRWLAWYQQKPEKAPKSLIYAASSLQSG
VPSRFSGSGSGTDFTLTISGLQPEDFATYYCQQYNSYPRTFGQGTKV
EIK
Immune-Stimulatory Compounds
[0304] In some embodiments, the immune-stimulatory conjugates described herein further comprise an immune-stimulatory compound. An immune-stimulatory compound can be a small molecule, a compound or molecule that binds to a protein target and can activate the target protein's function, or a compound that binds to a protein target and can inhibit the protein target's function, resulting in immune stimulation or modulation. In certain embodiments, an immune-stimulatory compound of a conjugate (i.e., attached to an antibody construct either directly or via a linker) can stimulate or activate its protein target with no or minimal processing of the conjugate. In certain embodiments, an immune-stimulatory compound of a conjugate (i.e., attached to an antibody construct either directly or via a linker) can inhibit its protein target with no or minimal processing of the conjugate. In this context, processing refers to degradation of the antibody construct or cleavage of the linker to liberate the immune-stimulatory compound or degredation product of the conjugate containing the immune-stimulatory compound. In certain embodiments, the protein target of the immune-stimulatory compound is an extracellular protein target and is located on the cell surface membrane or cellular compartments in communication with the cell surface, such as in the endoplasmic reticulum (ER). In certain embodiments, the protein target is intracellular, such as in the cytoplasm.
[0305] In some embodiments, an immune-stimulatory compound can activate immune cells. In some embodiments, an immune-stimulatory compound can reduce inhibition of immune cells. In some embodiments, an immune-stimulatory compound can stimulate immune activation by triggering degradation of a protein target.
[0306] In some embodiments, an immune-stimulatory compound can be a molecule or compound whose action on its target can lead to immune stimulation by direct immune cell activation. In some embodiments, the immune activation can be indirect by alteration of the immune suppressive microenvironment of a tumor (e.g., removing an immunosuppressive signal or altering an immunosuppressive state). In some embodiments, the immune-stimulatory compound's activity can be both direct and indirect. In certain embodiments, an immune-stimulatory conjugate can alter the activity of its protein target in cells having an antigen bound by the conjugate as compared to activity of the protein target in non-antigen bearing cells (i.e., the immune-stimulatory activity is antigen-specific).
[0307] In certain embodiments, the immune-stimulatory compound can be coupled to an Fc domain or other portion of an antibody construct via a linker. In each of the embodiments described herein, the immune-stimulatory compound can be coupled to the antibody construct via a linker.
[0308] An immune-stimulatory compound can be a Pattern recognition receptor (PRR) agonist.
Pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). A PRR can be membrane bound.
A PRR can be cytosolic. A PAMP molecule can be a toll-like receptor agonist. A
PRR can be a toll-like receptor (TLR). A PRR can be RIG-I-like receptor. A PRR can be a receptor kinase. A
PRR can be a C-type lectin receptor. A PRR can be a NOD-like receptor. A PRR
can be TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, or TLR13.
[0309] A PRR agonist can be a damage-associated molecular pattern (DAMP) molecule. A
DAMP molecule can be an intracellular protein. A DAMP molecule can be a heat-shock protein.
A DAMP molecule can be an HMGB1 protein. A DAMP molecule can be a protein derived from the extracellular matrix that is generated after tissue injury. A DAMP
molecule can be a hyaluronan fragment. A DAMP molecule can be DNA. A DAMP molecule can be RNA. A

DAMP molecule can be an S100 molecule. A DAMP molecule can be a nucleotide(s).
A DAMP
molecule can be ATP. A DAMP molecule can be a nucleoside(s). A DAMP molecule can be an adenosine. A DAMP molecule can be uric acid.
[0310] In some embodiments, the immune-stimulatory compound can be a Toll-like receptor agonist, a RIG-I agonist, a STING agonist, a GPCR agonist, an ion channel agonist, a membrane transporter agonist, an ER protein agonist, a beta-catenin pathway inhibitor, a kinase inhibitor, a TNIK inhibitor, a Tankyrase inhibitor, a GPCR antagonist, an HSP90 inhibitor, or an AAA-ATPase p97 inhibitor. In some embodiments, the immune-stimulatory compound can be a Toll-like receptor agonist, a RIG-I agonist or a STING agonist. In some embodiments, the immune-stimulatory compound can be a beta-catenin pathway inhibitor, such as a TNIK
inhibitor or a Tankyrase inhibitor.
[0311] In some embodiments, the immune-stimulatory compound is a Toll-like receptor agonist.
A toll-like receptor agonist can be any molecule that acts as an agonist to at least one toll-like receptor. In some embodiments, the Toll-like receptor agonist can be a molecule selected from a CpG oligonucleotide, Poly G10, Poly G3, Poly I:C, a lipopolysaccharide, a zymosan, a bacterial flagella protein (e.g., flagellin), Pam3CSK4, PamCysPamSK4, dsRNA, ssRNA, a diacylated lipopeptide, a bacterial lipoprotein, a triacylated lipoprotein, lipoteichoic acid, or a peptidoglycan (such as a bacterial peptidoglycan).
[0312] In some embodiments, an immune-stimulatory compound is not a toll-like receptor agonist. In some embodiments, a toll-like receptor agonist is not a naturally occurring molecule, such as CpG oligonucleotide, a lipopolysaccharide, a zymosan, a bacterial flagella protein (e.g., flagellin), Pam3CSK4, PamCysPamSK4, dsRNA, ssRNA, a diacylated lipopeptide, a bacterial lipoprotein, a triacylated lipoprotein, lipoteichoic acid, or a peptidoglycan (such as a bacterial peptidoglycan). In some further embodiments, a toll-like receptor agonist is not a synthetic nucleic acid, such as Poly G10, Poly G3 or Poly I:C.
[0313] In some embodiments, a toll-like receptor agonist can be a synthetic small molecule. A
toll-like receptor agonist can be imiquimod. A toll-like receptor agonist can be CL307. A toll-like receptor agonist can be S-27609. A toll-like receptor agonist can be resiquimod. A toll-like receptor agonist can be UC-IV150. A toll-like receptor agonist can be gardiquimod. A toll-like receptor agonist can be motolimod. A toll-like receptor agonist can be a motolimod analog. A
toll-like receptor agonist can be VTX-1463. A toll-like receptor agonist can be GS-9620. A toll-like receptor agonist can be GSK2245035. A toll-like receptor agonist can be TMX-101. A toll-like receptor agonist can be TMX-201. A toll-like receptor agonist can be TMX-202. A toll-like receptor agonist can be isatoribine. A toll-like receptor agonist can be AZD8848. A toll-like receptor agonist can be MEDI9197. A toll-like receptor agonist can be 3M-051.
A toll-like receptor agonist can be 3M-852. A toll-like receptor agonist can be 3M-052. A
toll-like receptor agonist can be 3M-854A. A toll-like receptor agonist can be S-34240. A toll-like receptor agonist can be CL663. A toll-like receptor agonist can be KU34B.
[0314] A RIG-I agonist can be KIN1148. A RIG-I agonist can be SB-9200. A RIG-I
agonist comprises a 5'ppp-dsRNA.
[0315] In some embodiments, the immune-stimulatory compound can comprise a non-naturally occurring chemotype, such as a substituted pyrimidine, a substituted purine, a substituted guanine nucleoside, a substituted 8-oxoadenine, a substituted imidazoquinoline, a substituted thiazoquinoline, a substituted 2-aminoimidazole, a substituted furo[2,3-c]pyridine, a substituted pyrazine, a substituted furo[2,3-c]quinoline, a substituted 2-aminobenzimidazole, a substituted 2-aminoquinoline, or a substituted 2-aminobenzazepine.
[0316] In certain embodiments, the immune-stimulatory compound can comprise S-27609, CL307, UC-IV150, imiquimod, gardiquimod, resiquimod, motolimod, VTS-1463, GS-9620, GSK2245035, TMX-101, TMX-201, TMX-202, isatoribine, AZD8848, MEDI9197, 3M-051, 3M-852, 3M-052, 3M-854A, S-34240, KU34B, SB9200, SB11285, 8-substituted imidazo[1,5-a]pyridine, or CL663.
[0317] An immune-stimulatory compound can comprise an inhibitor of TGFbeta, Beta-Catenin, PI3K-beta, STAT3, IL-10, IDO or TDO. The immune-stimulatory compound can comprise LY2109761, GSK263771, iCRT3, iCRT5, iCRT14, LY2090314, CGX-1321, PRI-724, BC21, ZINCO2092166, LGK974, IWP2, LY3022859, LY364947, SB431542, AZD8186, SD-208, indoximod (NLG8189), F001287, GDC-0919, epacadostat (INCB024360), RG70099, 1-methyl-L-tryptophan, methylthiohydantoin tryptophan, brassinin, annulin B, exiguamine A, PIM, LM10, 8-substituted 2-amino-3H-benzo[b]azepine-4-carboxamide, or INCB023843.
[0318] Additionally, stimulator of interferon genes (STING) can act as a cytosolic DNA sensor wherein cytosolic DNA and unique bacterial nucleic acids called cyclic dinucleotides are recognized by STING, and therefore STING agonists. In certain embodiments, the STING
agonist can comprise a cyclic dinucleotide. Other non-limiting examples of STING agonists include:

H

p0 OX5
[0319] , wherein in some embodiments, Xi=X2=0; X3=G; X4=G; X5=CO(CH2)12CH3; X6=2 TEAH; in some embodiments, X1=X2=S [Rp,Rp]; X3=G; X4=A; X5=H; X6=2 TEAH; in some embodiments, X1=X2=S
[Rp,Rp] ;
X3=A; X4=A; X5=H; X6=2 Na; in some embodiments, X1=X2=S [Rp,Rp] ; X3=A; X4=A;
X5=H;
X6=2 NH4; and in some embodiments, Xi=X2=0 ; X3=G; X4=A; X5=H; X6=2 TEAH;

N
0 \i .=S
C) ¨{ . Ck,õ 47 N li ,,JIN, = i \ = = e 1 s 1" t' '===='''%
0........ ;`,.

''''''w ' 3 . = 4.... 0 .N., A, 0., %.
õ..... 0 k , ,, i ,. . . .
x.õ...õ:õ...õ;\..4 ..... Ai ..."4=.0 (:$.1r- = r .>=f -...'"I'f..
s' \ ,i't . t,=.,,z`" N -.
i...1 yk N ltk42, ..tt ...t.k.= 34 . s';') . =
(., N .....,õ..L.,,,z.......0,,, il.t \t" *),,_..,i 5:, 0 tt . ti.,..- =,,,,*E , i <*.
\\,.....,,,c) 6( rk R t= e.,3 "'-'0.....4.,..0 .C.M.1 = ====,,,,,,,,o ,.. .;
ijii= \ S. = 4=-=,, - *`t..,..,..

=-=n===( N
'''''Nct 0 ,... ,..., , . =-...,1 i = ,, µi N 11%.
o = i 0 /1 t=
0.= 0 , wherein Ri=R2=H; Ri=propargyl, R2=H; Ri=H, R2=propargyl; Ri=allyl, R2=H;
Ri=H, R2=ally1;
Ri=methyl, R2=H; Ri=H, R2=methyl; Ri=ethyl, R2=H; Ri=H, R2=ethyl; Ri=propyl, R2=H; Ri=H, R2=propyl; Ri=benzyl, R2=H; Ri=H, R2=benzyl; Ri=myristoyl, R2=H; Ri=H, R2=myristoyl;
Ri=R2=heptanoyl; Ri=R2=hexanoyl; or Ri=R2=pentanoyl;
li % so , \ , N ttt=,zµ
11 k' / \\ , (f='*.
Na0=========<:). 1=1 i ' i.:,,N...;:' 34#
i 0 IN. .' ).' '''( _________________ I
N
, ""'"'" 3 . / õ ,..A.....õ... .,. õ
.õ.3õ..õ
õ ---1 -,....... µ,./....., .....s, , , , EV, rf.2isN.,) \ 11 1 NI.k.,õ,,,õ...N,4... 9* 7 , \ I
.......,,../ Nte`'NSH 1 ,. ,4.....,="C.,õ ...a:9 4 sk 0 0" o Nw=-===\
":"p \S ii,::',i=-=-=-=-=\.,.,.,.,.
-s------ ,.........,z, :. f,=..¨ ..õ4.:::=) __________ -,.... )......H =..,,, ,, µ,),/,:õ. s .õ,..,.... .
0 ..,..õ
1... ,,,),..,........1> tL, y "=,,,k ,
[0320] wherein Ri=R2=H; Ri=propargyl, R2=H; Ri=H, R2=propargyl; Ri=allyl, R2=H; Ri=H, R2=ally1; Ri=methyl, R2=H; Ri=H, R2=methyl; Ri=ethyl, R2=H; Ri=H, R2=ethyl;
Ri=propyl, R2=H; Ri=H, R2=propyl; Ri=benzyl, R2=H; Ri=H, R2=benzyl; Ri=myristoyl, R2=H;
Ri=H, R2=myristoyl; Ri=R2=heptanoyl; Ri=R2=hexanoyl; or Ri=R2=pentanoyl;
N34,, WI? NiiA
N N
t4 0.===={1 N
i \\.., 6i34z .. I ''..."( Nlik ,3, ...,L.,:j ""'n Ci,,v,e FIN'^^rAN 1 ========= t --s,õ4,0,p e ' .-* =.t.z K 11 1 ,!' >, ,,,.. i o 3c 4 '\=... ,==== \ p I o 0 st=a, 4.--f. '.: T,:k &.=
= t'= C> 3 L!. eA
ss-40.,==== .
t44,, N N
N "
%,.======<rs 1 / Um\ 14 \ V RI Nii, WI:
>=11 -= fi s ,1) N, .1, ..7 Ny.=
'''s,ti :.õ(e õ, , , .,,..õ........L.:
ti ti. ce $is.i li ts?. &; ,' 1 i I
N,...=-=1,µ, .13i t""'*c,ti".1 , 1-.....õ,..... &,,, L4 ' .3 0õ,..0 4V1e NY
,
[0321] wherein Ri=R2=H; Ri=propargyl, R2=H; Ri=H, R2=propargyl; Ri=allyl, R2=H; Ri=H, R2=ally1; Ri=methyl, R2=H; Ri=H, R2=methyl; Ri=ethyl, R2=H; Ri=H, R2=ethyl;
Ri=propyl, R2=H; Ri=H, R2=propyl; Ri=benzyl, R2=H; Ri=H, R2=benzyl; Ri=myristoyl, R2=H;
Ri=H, R2=myristoyl; Ri=R2=heptanoyl; Ri=R2=hexanoyl; or Ri=R2=pentanoyl;
X

rki 3 0 0-1)1,1:-011, , wherein each X is independently 0 or S, and R3 and R4 are each independently H or an optionally substituted straight chain alkyl of from 1 to 18 carbons and from 0 to 3 heteroatoms, an optionally substituted alkenyl of from 1-9 carbons, an optionally substituted alkynyl of from 1-9 carbons, or an optionally substituted aryl, wherein substitution(s), when present, may be independently selected from the group consisting of C1,6 alkyl straight or branched chain, benzyl, halogen, trihalomethyl, Ci_6alkoxy, ¨NO2, ¨NH2, ¨

OH, ¨0, ¨COOR - where R - is H or lower alkyl, ¨CH2OH, and ¨CONH2, wherein R3 and R4 are not both H;

---- , ..."

IA o k i \ I
immomm \ i S \
/ \
\
s i Bf .--...- 0-- P ----, I
4 , wherein Xi=X2=0; Xi=X2=S; or X1=0 and X2=S, T4 i '`....,'N
\
L

f \ I
/ OH
I \

P \
i N
r:õN ,._., :--- N___.----N . 0- ) =:::.=:,-) NE-t.
, 1 !
i a <7 H ,0---0-------. ---\ N=------`,. <-<:;* N.
HO -...,,V
\********* 1 i ..........,µ i p O. H
-..., ,..--...., -..., - - -- -.,............- S.S
t HN, : 3 i I
O , ..N.,,.. ....."."¨,=,,,õ
0 .

1 ..-=''' `-,,I
i.
.......µ .
\
I \

/
,----' tsi 1 0 \ Rp i 0 .....--;.: .=,.., i 1 s ' \.........,..,="^,..,i4=.,, N 1-i a , õN.,......,.. .õ...----..õ, -- NH
\
N------",,,, ...^-:::="'N.N
.1 RP
\ ..",. /

HO

µ
3-IA N, -,-...., =,--N
\
¨i HN

CS , Ntii.l.

/
'N-------\N --"`-----"' , ¨ S Pt '----.".8 \ '''"N

1., /
;
H
0 0,, õ
,õ0õ..., ./----\_ ,õ...,........._, ...Ø........,,,......,,,,..
,....õ, , /1 .

_..-= N
tst H), , a H
0- i \ i .-$ ...............
Hp p.--, \ N.----....., ...,5*---...., \ , , 0, i - N" .'N Hõ

k hi \
{
i \
i OH
-4) iip N.,¨.*
i I .4)\ -------ll --s-I
i , "õ =-=-=.õiõ...---. "---õiv ,,..i S" '''' I = 1"
C3=P-"' -Th, N---- -...õ, ,, 11.SP ..,.....õõo.õ, / N''' N H2 HO
i 1.....k / \
i \

i=-s. ......--k ;") /12N,,, 1 .-0- v =,-,---- N._--N 07-=
R..¨ ..
---$

,and N
,,,,e2 S-1 ,......,0--, \ 1 ,...---S--" Sp HO
o i \
\
17$ / OH
N i ''' 0 --' \_. Sp/
....--"...; N, re., ,......_ ¨ som,,,,.......v =._ 1\ 8 - N

i
[0322] In some embodiments, an immune-stimulatory compound can be a kinase inhibitor. An immune-stimulatory compound can inhibit one or more kinases.
[0323] An immune-stimulatory compound can be an inhibitor of ALK, Bcr-Abl, BRAF, BTK, c-KIT, EGFR, ErbB2, JAK, MEK, MET, PDGFRB, RET, ROS1, Syk, SRC, TGF(3122, TNIK, TNKS, TNKS2, TrkA, TrkB, TrkC, VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, FGFR3, FGFR4, CSF1R, RON/MST1R, TYR03, MERTK, AXL, PI310, PI3Ky, MAP4K1, PERK, KIT, or any combination thereof. An immune-stimulatory compound can be an inhibitor of TGF(3121, TGF(3122, TNIK, TNKS, PI3K-f3, STAT3, IL-10, IDO, or TDO.
[0324] In various embodiments, the immune-stimulatory compound comprises LY2109761, GSK263771, iCRT3, iCRT5, iCRT14, LY2090314, CGX-1321, PRI-724, BC21, ZINCO2092166, LGK974, IWP2, LY3022859, LY364947, SB431542, AZD8186, SD-208, indoximod (NLG8189), F001287, GDC-0919, epacadostat (INCB024360), RG70099, 1-methyl-L-tryptophan, methylthiohydantoin tryptophan, brassinin, annulin B, exiguamine A, PIM, LM10, INCB023843, or 8-substituted imidazo[1,5-a]pyridine.
[0325] An immune-stimulatory compound can be an agonist of a GPCR, an ion channel, a membrane transporter, or an ER protein.
[0326] An immune-stimulatory compound can be an antagonist of the GPCR A2aR, the sphingosine 1-phosphate receptor 1, prostaglandin receptor EP3, prostanglandin receptor E2, Frizzled, CXCR4, or an LPA receptor.
[0327] An immune-stimulatory compound can be an ion channel agonist for CRAC, Kv1.3, or KCa3.1.
[0328] An immune-stimulatory compound can be an inhibitor of HSP90 or AAA-ATPase p97.
Immune-Stimulatory Conjugate Properties
[0329] In certain embodiments, an immune-stimulatory compound of a conjugate (i.e, attached to an antibody construct either directly or via a linker) has a biological potency no less than at least about 0.33%, about 1%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% of the potency of the control (free) immune-stimulatory compound (i.e., not attached to an antibody construct).
[0330] The specificity of the antigen-binding domain (of a conjugate) for an antigen can be influenced by the attachment of an immune-stimulatory compound to an antibody construct. In various embodiments, an antigen-binding domain of the conjugate can bind to its antigen with at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% of the specificity of the antigen-binding domain for the antigen in the absence of attachment of the immune-stimulatory compound.
[0331] The specificity of the Fc domain (of a conjugate) for an Fc receptor can be influenced by the attachment site of an immune-stimulatory compound (directly or via a linker). In some embodiments, the Fc domain of a conjugate retains the specificity of the unconjugated Fc domain to bind to an Fc receptor. In specific embodiments, the Fc domain of the conjugate can bind to an Fc receptor with at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% of the specificity of the Fc domain to the Fc receptor in the absence of attachment of the immune-stimulatory compound.
[0332] In some embodiments, the Fc domain of a conjugate has an altered specificity for an Fc receptor relative to the corresponding unconjugated Fc domain. In specific embodiments, the Fc domain of the conjugate can bind to an Fc receptor with at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% loss of specificity of the Fc domain to the Fc receptor as compared to an Fc domain of a conjugate not attached to an immune-stimulatory compound (in the absence of the immune-stimulatory compound). In some embodiments, the Fc domain is an Fc null.
[0333] The affinity of the antigen-binding domain of a conjugate to an antigen can be influenced by the attachment of an immune-stimulatory compound attached to the antibody construct. In some embodiments, the affinity of the antigen-binding domain of the conjugate for binding to an antigen is at least about 1%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% of the affinity of the antigen-binding domain to the antigen in the absence of the immune-stimulatory compound (not attached to the antibody construct).
[0334] The affinity of the Fc domain to an Fc receptor of a conjugate can be influenced by attachment of an immune-stimulatory compound to the antibody construct (either directly or indirectly). In some embodiments, the Fc domain of the conjugate can bind to an Fc receptor with at least about 1%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% of the affinity of the Fc domain to the Fc receptor in the absence of the immune-stimulatory compound attached to the antibody construct. In some embodiments, the Fc domain of the conjugate can bind to an Fc receptor with a reduced affinity of at least about 1%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 85%, about 90%, about 95%, or about 100% of the affinity of the Fc domain to the Fc receptor in the absence of attachment the immune-stimulatory compound (directly or via a linker). In some embodiments, the Fc domain is an Fc null.
[0335] The Kd for binding of an antigen-binding domain to an antigen when an immune-stimulatory compound is attached to the antibody construct can be about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 15 times, about 20 times, about 25 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, about 100 times, about 110 times, or about 120 times greater than the Kd for binding of the antigen binding domain to the antigen in the absence of the immune-stimulatory compound attached to the antibody construct.
[0336] In some embodiments, the Kd for binding of an Fc domain to an Fc receptor when an immune-stimulatory compound is attached to an antibody construct can be about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 15 times, about 20 times, about 25 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, about 100 times, about 110 times, or about 120 times greater than the Kd for binding of the Fc domain to the Fc receptor without the immune-stimulatory compound attached to the antibody construct.
[0337] In some embodiments, the Kd for binding of an Fc domain to a Fc receptor when the immune-stimulatory compound is attached to the antibody construct can be about 2 times, about 3 times, about 4 times, about 5 times, about 6 times, about 7 times, about 8 times, about 9 times, about 10 times, about 15 times, about 20 times, about 25 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, about 100 times, about 110 times, or about 120 times less than the Kd for binding of the Fc domain to the Fc receptor when the immune-stimulatory compound is not attached to the antibody construct.
[0338] Affinity is the strength of the sum total of noncovalent interactions between a single binding site of a molecule, for example, an antibody, and the binding partner of the molecule, for example, an antigen. The affinity can also measure the strength of an interaction between an Fc domain of an antibody and an Fc receptor. Unless indicated otherwise, as used herein, "binding affinity" refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen or Fc domain and Fc receptor). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd). Affinity can be measured by common methods known in the art. Specific illustrative and exemplary embodiments for measuring binding affinity are described in the following.
[0339] In some embodiments, an antibody construct (e.g., an antibody or antigen-binding fragment thereof) can have a dissociation constant (Kd) for an antigen or Fc receptor of about 1 i.t.M, about 100 nM, about 10 nM, about 5 nM, about 2 nM, about 1 nM, about 0.5 nM, about 0.1 nM, about 0.05 nM, about 0.01 nM, or about 0.001 nM or less (e.g., 10-6 or less, 10-8 M or less, from 10-8M to 10-13 M, or from 10 M to 10-13 M). An affinity matured antibody can be an antibody with one or more alterations in one or more complementarity determining regions (CDRs), compared to a parent antibody, which may not possess such alterations, such alterations resulting in an improvement in the affinity of the antibody for antigen. These antibodies can bind to their antigen with a Kd of about 5x10-9 M, about 2x10-9 M, about 1x10-9 M, about 5x10-1 M, -. .-, about 1x10-10 m about 5x10- 1 1 M, about 1x10- 1 1 M, about 5x10-12 M, about 1x10-12 M, or less.
In some embodiments, the antibody construct (e.g., affinity matured antibody) can have an increased affinity of at least 1.5-fold, 2-fold, 2.5-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, or greater as compared to an antibody construct without alterations in one or more CDRs.
[0340] Kd can be measured by any suitable assay. For example, Kd can be measured by a radiolabeled antigen binding assay (RIA). For example, Kd can be measured using surface plasmon resonance assays (e.g., using a BIACOREC)-2000 or a BIACOREC)-3000).
[0341] The molar ratio or drug-antibody ratio of a conjugate refers to the number of immune-stimulatory compounds attached to an antibody construct in a conjugate or preparation of immune-stimulatory conjugates. The molar ratio can refer to the number of immune-stimulatory compounds attached (e.g., conjugated) to an antibody construct of a particular conjugate and is an integer, such as from 0-8 or 0 to 20. The molar ratio can also refer to the average number of immune-stimulatory compounds attached to antibody constructs in a mixture of conjugates, such as in a pharmaceutical composition.
[0342] The molar ratio can be determined, for example, by Liquid Chromatography/Mass Spectrometry (LC/MS), in which the number of immune-stimulatory compounds attached to the antibody construct can be directly determined. Additionally, as non-limiting examples, the molar ratio can be determined based on hydrophobic interaction chromatography (HIC) peak area, by liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS), by UV/Vis spectroscopy, by reversed-phase-HPLC (RP-HPLC), or by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS).
[0343] In some embodiments, the molar ratio of immune-stimulatory compound to antibody construct can be less than 8 or less than 20. In other embodiments, the molar ratio of immune-stimulatory compound to an antibody construct can be 8, 7, 6, 5, 4, 3, 2, or 1. In some embodiments, the average molar ratio of immune-stimulatory compounds to antibody constructs in a composition can be less than 8, such as about 3 to 5 or about 2. In other embodiments, the average molar ratio of immune-stimulatory compounds to antibody constructs in a composition can be 8, 7, 6, 5, 4, 3, 2, or 1 or fractions hereof, or such as about 3.5 or about 1.8.
[0344] In a conjugate, an antibody construct (e.g., an antibody) can be linked to an immune-stimulatory compound in such a way that the antibody construct can still bind to an antigen and the Fc domain of the antibody construct can still bind to an FcR. In a conjugate, an antibody construct can be linked to an immune-stimulatory compound in such a way that the linking does not interfere with the ability of the antigen binding domain of the antibody construct to bind to its antigen, the ability of the Fc domain of the antibody construct to bind to an FcR, or FcR-mediated signaling resulting from the Fc domain of the antibody construct binding to an FcR. In a conjugate, an immune-stimulatory compound can be linked to an antibody construct in such a way that the linking does not interfere with the ability of the immune-stimulatory compound to bind to its receptor or otherwise can induce a biological effect. In some embodiments, a conjugate can produce stronger immune stimulation and a greater therapeutic window than components of the conjugate alone. For example, in an anti-tumor or anti-CD40 antibody linked to a TLR agonist, the combination of CD40 agonism, TLR agonism and an accessible Fc domain of the anti-CD40 antibody resulting in FcR-mediated signaling can produce stronger immune stimulation and a greater therapeutic window than the CD40 agonism, TLR
agonism, or the FcR-mediated signaling alone.
[0345] In some embodiments, a conjugate can comprise a first binding domain, wherein the first binding domain contributes to immune-stimulatory activity; a first and second binding domain, wherein the second binding domain contributes to immune stimulatory activity;
or a first binding domain and second binding domain, wherein the first binding domain and the second binding domain contribute to immune-stimulatory activity. The first binding domain and the second binding domain can contribute to the same immune-stimulatory activity. The first binding domain and the second binding domain can contribute to different immune-stimulatory activities.
[0346] In some embodiments, a conjugate in which the first binding domain contributes to immune-stimulatory activity can increase the immune-stimulation of the conjugate.
Immune-Stimulatory Compound Potency and Binding Activity
[0347] In certain embodiments, an immune-stimulatory compound has similar activity when bound to the antibody construct as when not bound to the antibody construct.
In certain embodiments, the immune-stimulatory compound maintains the same level of potency and/or binding affinity when bound to an antibody construct as compared to the unbound immune-stimulatory compound.
[0348] For many known antibody-drug conjugates, the payload/drug of the conjugate is a cytotoxic agent that acts on an intracellular target. The antibody generally targets a certain tumor marker on the surface of a cancer cell and upon binding of the antibody to the tumor cell, the cancer cell then internalizes the antibody-cytotoxic agent conjugate. The cytotoxic agent is released within the cell through enzymatic cleavage or other cleavage of the agent's linkage to the antibody or through enzymatic degradation of the antibody. The released cytotoxic agent or degredation product acts on the intracellular target of the cytotoxic agent to kill the cancer cell.
Important to the mechanism of action of many antibody-cytotoxic agent conjugates is: (1) that the cytotoxic agent is bound to the antibody with a linker, wherein the linker is not cleaved until exposed to enzymes or conditions inside a target cell, e.g., a cancer cell;
(2) that the cytotoxic agent is released from the antibody inside of the cell to perform its cytotoxic function; and (3) that the cytotoxic agent is not active or minimally active (i.e., in a prodrug form) when bound to the antibody such that the cytotoxic agent does not indiscriminately kill cells and harm organ systems distributed thorught the body on the path to the cancer cell.
[0349] In certain aspects, the immune-stimulatory conjugates of the disclosure operate under a different paradigm from such antibody-cytotoxic agent conjugates. The immune-stimulatory conjugates of the disclosure can be designed in a way that the payload immune-stimulatory compound has the same potency, similar potency, or increased potency when bound to the antibody construct as compared to the unbound immune-stimulatory compound and in contrast to antibody-cytotoxic agent conjugates. The immune-stimulatory conjugates of the disclosure may perform, and in some cases preferably perform, the intended function of the compound, i.e., stimulate or modulate the function of immune cells or other target cells, without prior release of the compound from the conjugate (i.e., while attached to the antibody construct). The features of the immune-stimulatory compound-conjugates and assays that enable these functions and others are described further herein.
[0350] The potency of the immune-stimulatory compound of the conjugate may not be significantly reduced relative to the potency of the un-attached (free) immune-stimulatory compound. In particular, the potency of the immune-stimulatory compound of the conjugate (i.e., as part of the conjugate or covalently bound to the antibody construct) is preferably no greater than 500-fold less, no greater than 400-fold less, no greater than 300-fold less, no greater than 200-fold less, no greater than 100-fold less, no greater than 50-fold less, or no greater than 10-fold less than the potency of a control compound, wherein the control compound is the unbound immune-stimulatory compound. For example, for an immune-stimulatory conjugate represented by the structure: Ab ¨ L ¨ C, wherein A is an antibody construct, L is a linker, and C is an immune-stimulatory compound, the immune-stimulatory activity of C of the conjugate A ¨ L ¨ C

is preferably no greater than 500-fold less, no greater than 400-fold less, no greater than 300-fold less, no greater than 200-fold less, no greater than 100-fold less, no greater than 50-fold less, or no greater than 10-fold less than the potency of the immune-stimulatory compound, C, unbound from the immune-stimulatory conjugate, A ¨ L ¨ C, in the absence of processing of the immune-stimulatory conjugate in a cell.
[0351] In particular embodiments, the potency of an immune-stimulatory compound of the conjugate (i.e., covalently bound to the antibody construct) is near or equivalent to the potency of the unbound immune-stimulatory compound, such as within about 10-fold, within about 8-fold, within about 5-fold, or within about 2-fold of the potency of the unbound immune-stimulatory compound. The potency of the immune-stimulatory compound of the conjugate may be greater than the potency of the unbound immune-stimulatory compound, such as about 2-fold or greater, 5-fold or greater, 10-fold or greater, 100-fold or greater, 200-fold or greater, 300-fold or greater, 400-fold or greater, or even 500-fold or greater than the potency of the unbound immune-stimulatory compound. In certain embodiments, the tolerability of an immune-stimulatory compound when part of a construct is greater than the tolerability of the unbound immune-stimulatory compound in a subject.
[0352] In certain embodiments, the potency of the immune-stimulatory compound when bound to a 5-500 atom linker is the same, similar, or increased as compared to the potency of the immune-stimulatory compound not bound to the 5-500 atom linker. In certain embodiments, the tolerability of the immune-stimulatory compound in a subject when bound to a 5-500 atom linker is the same, similar, or increased as compared to the tolerability of the immune-stimulatory compound not bound to the 5-500 atom linker.
[0353] The "5-500 atom linker" referred to herein has 5 to 500 consecutive atoms from end to end. When attached to an immune-stimulatory compound and to an antibody construct, a 5-500 atom linker has 5-500 consecutive atoms between the point of attachment to the immune-stimulatory compound and the point of attachment to the antibody construct. A
5-500 atom linker can have, for example, from about 50 to about 500 atoms, such as about 50 to about 300 atoms or such as about 50 to about 200 atoms. A 5-500 atom linker can have, for example, from about 25 to about 500 atoms, such as about 25 to about 300 atoms or such as about 25 to about 200 atoms. In certain embodiments, the linker includes one or more peptide bonds. In certain embodiments, the linker includes one or more ethylene glycol groups. In certain embodiments, the linker includes a peptide backbone and one or more side chains. In certain embodiments, the linker is not cleaved from the immune-stimulatory compound in the assay evaluating potency.
[0354] Exemplary 5-500 atom linkers include Fleximer linkers, linkers with one or more carbamate or amide linkages and linkers represented by the formula:

Rx 0 Rx Ra Ra 0-7 H 0-9 , , F
0 0 NjOC)(C) F
Nj.LHN 0-7 Rx F
or N peptide ¨Rx H , wherein 12' is a reactive moiety for attachment to the antibody construct, 12a is hydrogen, Ci_loalkyl, sulfonate and methyl sulfonate and the wavy line indicates an attachment to the rest of the linker or to the immune-stimulatory compound.
[0355] In some embodiments, the linker is a non-cleavable linker. Examples of non-cleavable linkers include the following:
Rx 0 Rx Ra Ra 0-7 H 0-9 , , F
0 0 NjOC)(C) F
Nj.LHN 0-7 Rx F
wherein 12' is a reactive moiety for attachment to the antibody construct, 12a is hydrogen, Ci_ malkyl, sulfonate and methyl sulfonate and the wavy line indicates an attachment to the rest of the linker or to the immune-stimulatory compound.
[0356] Further examples of non-cleavable linkers include:

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Claims (82)

WHAT IS CLAIMED IS:
1. An immune-modulatory conjugate comprising:
(a) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to a first antigen;
(b) a proteolysis targeting module, comprising:
(i) a protein targeting moiety that binds to a target protein;
(ii) an E3 ubiquitin ligase binding moiety; and (iii) a spacer S that is covalently bound to the protein targeting moiety and to the E3 ubiquitin ligase binding moiety, wherein the spacer is optionally has 1-25 consecutive non-hydrogen atoms; and (c) a linker L that is covalently attached to the antibody construct and to the proteolysis targeting module.
2. The conjugate of claim 1, wherein the conjugate is represented by one of the following formulae:
wherein:
Ab is the antibody construct;
L is the linker;
ULM is the E3 ubiquitin ligase binding moiety;
IMC is the protein targeting moiety and comprises an immune-modulatory compound;
S is the spacer;
n is selected from 1 to 20; and z is selected from 1 to 20.
3. The conjugate of any one of claims 1 to 2, wherein the Fc domain is an Fc null.
4. The conjugate of any one of claims 1 to 3, wherein the E3 ubiquitin ligase is selected from the group consisting of E3 ubiquitin ligase, such as Von Hippel-Lindaue E3 ubiquitin ligase (VHL), cereblon, mouse double minute 2 homolog (MDM2), AMFR, APC/Cdc20, APC/Cdh1, C6orf157, Cb1, CBLL1, CHFR, CHIP, DTL (Cdt2), E6-AP, HACE1, HECTD1, HECTD2, HECTD3, HECW1, HECW2, HERC2, HERC3, HERC4, HERC5, HUWE1, HYD, ITCH, LNX1, mahogunin, MARCH-I, MARCH-II, MARCH-III, MARCH-IV, MARCH-VI, MARCH-VII, MARCH-VIII, MARCH-X, MEKK1, MIB1, MIB2, MycBP2, NEDD4, NEDD4L, Parkin, PELI1, Pirh2, PJA1, PJA2, RFFL, RFWD2, Rictor, RNF5, RNF8, RNF19, RNF190, RNF20, RNF34, RNF40, RNF125, RNF128, RNF138, RNF168, SCF/.beta.-TrCP, SCF/FBW7, SCF/Skp2, SHPRH, SIAH1, SIAH2, SMURF1, SMURF2, TOPORS, TRAF6, TRAF7, TRIM63, UBE3B, UBE3C, UBR1, UBR2, UHRF2, WWP1, WWP2, and ZNRF1.
5. The conjugate of claim 4, wherein the E3 ubiquitin ligase binding moiety binds to VHL, cereblon, or MDM2.
6. The conjugate of any one of claims 1 to 5, wherein the protein targeting moiety binds to a protein selected from one of the groups consisting of:

a) an aryl hydrocarbon receptor, androgen receptor, estrogen receptor, FK506-binding protein 12, fibroblast growth factor receptor substrate 2, phosphatidylinositol -4,5-biphosphate 3-kinase, SMAD family member 3, bromodomain and extra-territorial family of proteins (BET), bromodomain-containing protein 4 member of the BET
family, Abelson tyrosine kinase, receptor-interacting serine/threonine-protein kinase 1, estrogen-related receptor, and transforming growth factor beta (TGFP); or b) ALK, Bcr-Abl, BRAF, BTK, c-KIT, EGFR, ErbB2, JAK, MEK, MET, PDGFRB, RET, ROS1, Syk, SRC, TNIK, TNKS, TNKS2, TrkA, TrkB, TrkC, VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, FGFR3, FGFR4, CSF1R, RON/MST1R, TYRO3, MERTK, AXL, PI3K, PI3K, MAP4K1, PERK, and KIT; or c) TGF.beta.R2, TGF.beta.R1, SMAD2, SMAD3, SMAD4, beta-catenin, CREBB2, Beta catenin/TCF4, beta catenin/LEF, beta catenin/CREBBP, YAP, TAZ, YAP/TAZ, TNKS1, TNKS2, MST1, MST2, NRAS, HRAS, KRAS, RASmut12, RASmut13, PERK (EIF2AK3), RON/MST1R, STAT3, MCT1, MCT2, and MCT4; or d) CSFR1, RON/MST1, PI3Kd, PI3Kg, PARP1, PD-L1, PP2A, A2ar, TYRO3, AXL, and MER.
7. The conjugate of any one of claims 1 to 6, wherein the first antigen is a tumor antigen.
8. The conjugate of claim 7, wherein the first antigen is selected from the group consisting of MUC16, CDS, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC, HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, Ley, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, .alpha.v.beta.3, WT1, LMP2, HPV E6, HPV E7, EGFRvIII, Her-2/neu, MAGE A3, p53 nonmutant, NY-ESO-1, Me1anA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyronsinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint fusion protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin B1, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE A1, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, Page4, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2, TRAIL1, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, MUC15, CA6, NAPI2B, TROP2, CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, LIV1, ROR1, and Fos-related antigen 1.
9. The conjugate of any one of claims 1 to 6, wherein the first antigen is an immune cell antigen.
10. The conjugate of claim 9, wherein the immune cell antigen is an antigen present on the surface of an antigen presenting cell selected from a dendritic cell and a macrophage.
11. The conjugate of any one of claims 9 to 10, wherein the immune cell antigen is selected from the group consisting of CD40, DEC-205, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX4OL, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, and CD32B.
12. The conjugate of any one of claims 1 to 10, wherein the protein targeting moiety is selected from a peptide and a non-proteinaceous molecule.
13. The conjugate of any one of claims 1 to 12, wherein the proteolysis targeting module is selected from compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, and 2-1.
14. The conjugate of any one of claims 1 to 13, wherein L is a cleavable linker.
15. The conjugate of any one of claims 1 to 13, wherein L is a non-cleavable linker.
16. The conjugate of any one of claims 1 to 15, wherein L is selected from:
, wherein G is an antibody construct linking moiety, G-wavy line indicates a bond of G to the antibody construct, peptide is selected from 1 to 10 amino acids, Ra is selected from hydrogen, Ci_loalkyl, sulfonate and methyl sulfonate, and the wavy line at the left side indicates a bond to the remainder of the linker.
17. The conjugate of claim 16, wherein G comprises a succinimide or a hydrolyzed succinimide.
18. The conjugate of any one of claims 1 to 17, wherein L is covalently bound to the antibody construct at a cysteine residue, an engineered cysteine residue, a lysine residue, a glutamate residue, or a glutamine residue of the antibody construct or is covalently bound to the antibody construct using a Sortase linker.
19. The conjugate of any one of claims 1 to 18, wherein the spacer S is an optionally substituted C1-25 alkylene or optionally substituted C1-25 heteroalkylene, wherein the heteroalkylene is a C1-24 alkylene chain interspersed with one or more groups independently selected from: -O-, -S-, -NH2-, and -C(O)NH-; and optionally substituted with a reactive group, RX, that can form a functional group selected from an amide bond, an ester bond, an ether bond, a carbonate bond, a carbamate bond, or a thioether bond.
20. The conjugate of any one of claims 1 to 19, wherein the antibody construct further comprises a second binding domain.
21. The conjugate of claim 20, wherein the second binding domain specifically binds to an antigen on an immune cell.
22. The conjugate of claim 21, wherein the immune cell antigen is selected from the group consisting of CD40, PD-1, PD-L1, DEC-205, CD36 mannose scavenger receptor 1, CLEC9A, DC-SIGN, CLEC12A, BDCA-2, OX40L, 41BBL, CD204, MARCO, CLEC5A, Dectin 1, Dectin 2, CLEC10A, CD206, CD64, CD32A, CD16A, HVEM, and CD32B.
23. The conjugate of any one of claims 20 to 22, wherein the second binding domain is attached to the antibody construct at a C-terminal end of the Fc domain.
24. The conjugate of any one of claims 11 to 23, wherein the Fc domain is an Fc domain variant comprising at least one amino acid residue change as compared to a wild type sequence of the Fc domain.
25. The conjugate of claim 24, wherein the Fc domain is an Fc domain variant that decreases binding of the Fc domain to an Fc receptor.
26. The conjugate of claim 24, wherein the at least one amino acid residue change is:
a) F243L, R292P, Y300L, L235V, and P396L, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898;
b) 5239D and I332E, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898; or c) S298A, E333A, and K334A, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898.
27. The conjugate of claim 24, wherein the at least one amino acid residue change is:
a) N297A, N297G, N297Q, N297D as in Eu index of Kabat numbering and relative to SEQ ID NO: 898; or b) K322A/L234A/L235A N296A as in the EU index of Kabat numbering and relative to SEQ ID NO: 898; or c) L234F/L235E/P331S N296A as in the EU index of Kabat numbering and relative to SEQ ID NO: 898; or d) P329G/L234A/L235A as in the EU index of Kabat numbering and relative to SEQ ID NO: 898.
28. A pharmaceutical composition, comprising the conjugate of any one of claims 1 to 27 and a pharmaceutically acceptable excipient.
29. The pharmaceutical composition of claim 28, wherein the average ratio of proteolysis targeting modules to antibody construct in the conjugate is from 2 to 6, from 3 to 5, or 1 to 3.
30. The pharmaceutical composition of one of claims 28 to 29, which is lyophilized.
31. A method of treating cancer, comprising administering the conjugate of any one of claims 1 to 27 or the pharmaceutical composition of any one of claims 28 to 30 to a subject in need thereof.
32. The method of claim 31, wherein the cancer is a solid tumor.
33. The method of claim 32, wherein the solid tumor is breast cancer, pancreatic cancer, colorectal cancer, renal cell cancer, gastric cancer, or lung cancer.
34. The method of any one of claims 31 to 33, wherein the pharmaceutical composition is administered parenterally.
35. The method of any one of claims 31 to 33, wherein the pharmaceutical composition is administered intravenously.
36. The use of the conjugate of any one of claims 1 to 27 in the preparation of a medicament for the treatment of cancer.
37. An immune-stimulatory conjugate comprising:
a) an immune-modulatory compound that binds to a protein active site of an intracellular protein target to stimulate an immune response by degradation of the protein target;
b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to a first antigen expressed on cells having the intracellular protein target; and c) a linker, wherein the linker is covalently bound to the antibody construct and the linker is covalently bound to the immune-modulatory compound; wherein the linker is optionally a linker having 5-100 consecutive atoms; wherein the K d for binding of the immune-modulatory compound, attached to the antibody construct of the conjugate, to the protein active site is equal to, or up to no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the IC50 of the immune-modulatory compound, attached to the antibody construct of the conjugate, is no greater than 300-fold the IC50 of a control compound, wherein the control compound is the unbound immune-modulatory compound.
38. The immune-stimulatory conjugate of claim 37, wherein the Fc domain is an Fc null.
39. The immune-stimulatory conjugate of claim 37, wherein the Fc domain binds to an Fc receptor and the dissociation constant (Kd) for binding of the Fc domain of the conjugate to the Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct.
40. The immune-stimulatory conjugate of any one of claims 37 to 39, wherein the EC50 or IC50 of the immune-modulatory compound attached to the antibody construct of the conjugate is no greater than 10-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-modulatory compound.
41. The immune-stimulatory conjugate of any one of claims 37 to 40, wherein the EC50 or IC50 of the immune-modulatory compound attached to the antibody construct of the conjugate is equivalent to or less than the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-modulatory compound.
42. The immune-stimulatory conjugate of any one of claims 37 to 41, wherein the conjugate further comprises an E3 ubiquitin ligase binding moiety.
43. The immune-stimulatory conjugate of claim 42, wherein the E3 ubiquitin ligase binding moiety binds to VHL, cereblon or MDM2
44. The immune-stimulatory conjugate of any one of claims 42 to 43, wherein the E3 ubiquitin ligase binding moiety is selected from compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, and 2-1.
45. The immune-stimulatory conjugate of any one of claims 42 to 44, wherein the E3 ubiquitin ligase binding moiety is attached to the immune-modulatory compound through a spacer, optionally a 1-25 atom spacer, and the spacer is bound through the 5-100 atom linker to the antibody construct.
46. The immune-stimulatory conjugate of any one of claims 37 to 45, wherein the immune-modulatory compound is a kinase inhibitor and the protein active site is a kinase active site.
47. The immune-stimulatory conjugate of claim 46, wherein the linker is covalently bound to the kinase inhibitor at a position on the kinase inhibitor that is at or near the solvent interface of the kinase active site as determined by modeling of the kinase inhibitor in the kinase active site.
48. The immune-stimulatory conjugate of claim 46, wherein the linker is covalently bound to the kinase inhibitor at a position on the kinase inhibitor such that when the kinase inhibitor is bound to the active site, the linker extends out from the kinase active site into the solvent, as determined by modeling of the kinase inhibitor in the kinase active site.
49. The immune-stimulatory conjugate of any one of claims 46 to 48, wherein the kinase inhibitor is selected from an inhibitor of ALK, Bcr-Abl, BRAF, BTK, c-KIT, EGFR, ErbB2, JAK, MEK, MET, PDGFRB, RET, ROS1, Syk, SRC, TGF.beta.R2, TNIK, TNKS, TNKS2, TrkA, TrkB, TrkC, VEGF, VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2, FGFR3, FGFR4, CSF1R, RON/MST1R, TYRO3, MERTK, AXL, PI3K.delta., PI3K.gamma., MAP4K1, PERK, and combinations thereof.
50. The immune-stimulatory conjugate of any one of claims 37 to 45, wherein the linker is covalently bound to the immune-modulatory compound at a site on the compound that does not interfere with binding of the compound to the protein active site.
51. An immune-stimulatory conjugate comprising:
(a) an immune-stimulatory compound that binds to a protein active site of a protein to stimulate an immune response, wherein the protein is present on the extracellular membrane or in the endoplasmic reticulum of a cell;

(b) an antibody construct comprising an antigen binding domain and an Fc domain, wherein the antigen binding domain binds to a first antigen; and (c) a linker having 5-100 consecutive atoms, wherein the linker is covalently bound to the antibody construct and the linker is covalently bound to the immune-stimulatory compound; and wherein the Kd for binding of the immune-stimulatory compound, attached to the antibody construct of the conjugate, to the protein active site is no greater than 100 times the Kd for binding of a control compound to the protein active site or wherein the EC50 or IC50 of the immune-stimulatory compound, attached to the antibody construct of the conjugate, is no greater than 300-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound.
52. The immune-stimulatory conjugate of claim 51, wherein the Fc domain is an Fc null.
53. The immune-stimulatory conjugate of claim 51, wherein the Fc domain binds to an Fc receptor and the dissociation constant (Kd) for binding of the Fc domain of the conjugate to an Fc receptor is equal to, or up to no greater than about 100 times the Kd for binding of a control antibody construct to the Fc receptor, wherein the control antibody construct is the unconjugated antibody construct.
54. The immune-stimulatory conjugate of any one of claims 51 to 53, wherein the EC50 or IC50 of the immune-stimulatory compound, when bound to the antibody construct by the 5-100 atom linker, is no greater than 10-fold the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound.
55. The immune-stimulatory conjugate of any one of claims 51 to 54, wherein the EC50 or IC50 of the immune-stimulatory compound, when bound to the antibody construct by the 5-100 atom linker, is equivalent to or less than the EC50 or IC50 of a control compound, wherein the control compound is the unbound immune-stimulatory compound.
56. The immune-stimulatory conjugate of any one of claims 51 to 55, wherein the immune-stimulatory compound is a toll-like receptor agonist, STING agonist, or RIG-I
agonist.
57. The immune-stimulatory conjugate of claim 56, wherein the immune-stimulatory compound is a toll-like receptor agonist selected from a TLR1 agonist, a TLR2 agonist, a TLR3 agonist, a TLR4 agonist, a TLR5 agonist, a TLR6 agonist, a TLR7 agonist, a TLR8 agonist, a TLR9 agonist, or a TLR10 agonist.
58. The immune-stimulatory conjugate of any one of claims 51 to 57, wherein the immune-stimulatory compound is selected from a pyrimidine, a purine, a guanine nucleoside, an 8-oxoadenine, an imidazoquinoline, a thiazoquinoline, a 2-aminoimidazole, a furo[2,3-c]pyridine, a furo[2,3-c]quinoline, a 2-aminobenzimidazole, a 2-aminoquinoline, and a 2-aminobenzazepine.
59. The immune-stimulatory conjugate of any one of claims 51 to 55, wherein the target of the immune-stimulatory compound is a GCPR, an ion channel, a membrane transporter, a phosphatase or an ER protein.
60. The immune-stimulatory conjugate of any one of claims 51 to 55, wherein the immune-stimulatory compound is an antagonist of the GPCR A2aR, the sphingosine 1-phosphate receptor 1, prostaglandin receptor EP3, prostanglandin receptor E2, Frizzled, CXCR4 or an LPA receptor.
61. The immune-stimulatory conjugate of any one of claims 51 to 55, wherein the immune-stimulatory compound is an ion channel agonist for CRAC, Kv1.3 or KCa3.1.
62. The immune-stimulatory conjugate of any one of claims 51 to 55, wherein the immune-stimulatory compound is an inhibitor of HSP90 or AAA-ATPase p97.
63. The immune-stimulatory conjugate of any one of claims 51 to 62, wherein the conjugate has immune-stimulatory activity with no or minimal cell processing of the conjugate.
64. The immune-stimulatory conjugate of any one of claims 51 to 63, wherein the linker is a non-cleavable linker.
65. The immune-stimulatory conjugate of any one of claims 51 to 63, wherein the linker is a Fleximer linker.
66. The immune-stimulatory conjugate of any one of claims 51 to 63, wherein the linker comprises a carbamate and one or more amide linkages.
67. The immune-stimulatory conjugate of any one of claims 37 to 66, wherein the linker is represented by the formula , wherein R x is a reactive moiety and wherein Ra is hydrogen, alkyl, sulfonate and methyl sulfonate.
68. The immune-stimulatory conjugate of any one of claims 37 to 67, wherein the linker is attached to the antibody construct at a cysteine or lysine residue of the antibody construct.
69. The immune-stimulatory conjugate of any one of claims 37 to 68, wherein the first antigen is a tumor antigen.
70. The immune-stimulatory conjugate of any one of claims 37 to 69, wherein the first antigen is at least 80% homologous to CD5, CD19, CD20, CD25, CD37, CD30, CD33, CD45, CAMPATH-1, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, MUC15, MUC16, folate-binding protein, A33, G250, prostate-specific membrane antigen (PSMA), ferritin, GD2, GD3, GM2, LeY, CA-125, CA19-9, epidermal growth factor, p185HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), tenascin, a metalloproteinase, endosialin, vascular endothelial growth factor, .alpha.v.beta.3, WT1, LMP2, HPV E6 E7, Her-2/neu, p53 nonmutant, NY-ESO-1, MelanA/MART1, Ras mutant, gp100, p53 mutant, PR1, bcr-abl, tyrosinase, survivin, PSA, hTERT, a Sarcoma translocation breakpoint protein, EphA2, PAP, ML-IAP, AFP, ERG, NA17, PAX3, ALK, androgen receptor, cyclin B1, polysialic acid, MYCN, RhoC, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, MAGE A1, MAGE A3, sLe(animal), CYP1B1, PLAV1, GM3, BORIS, Tn, GloboH, ETV6-AML, NY-BR-1, RGS5, SART3, STn, Carbonic anhydrase IX, PAX5, 0Y-TES1, Sperm protein 17, LCK, HMWMAA, AKAP-4, 55X2, XAGE 1, Legumain, Tie 3, VEGFR2, MAD-CT-1, PDGFR-B, MAD-CT-2, ROR2õ TRAIL1, MAGE A4, MAGE C2, GAGE, EGFR, CMET, HER3, EPCAM, CA6, NAPI2B, TROP2, Claudin-6 (CLDN6), Claudin-16 (CLDN16), CLDN18.2, RON, LY6E, FRA, DLL3, PTK7, Uroplakin-1B (UPK1B), LIV1, ROR1, STRA6, TMPRSS3, TMPRSS4, TMEM238, C1orf186, Fos-related antigen 1, VEGFR1, endoglin, PD-L1, VTCN1 (B7-H4), VISTA, gpNMB, or any fragment thereof.
71. The immune-stimulatory conjugate of any one of claims 37 to 70, wherein the antibody construct further comprises a second target binding domain.
72. The immune-stimulatory conjugate of claim 71, wherein the target binding domain specifically binds an immune cell.
73. The immune-stimulatory conjugate of claim 71 or 72, wherein the target binding domain is attached to the antibody construct at a C-terminal end of the Fc domain.
74. The immune-stimulatory conjugate of any one of claims 37 to 73, wherein the antibody construct is an antibody.
75. The immune-stimulatory conjugate of claim 74, wherein the antibody construct is a human antibody or a humanized antibody.
76. The immune-stimulatory conjugate of any one of claims 37 to 75, wherein the Fc domain is an Fc domain variant comprising at least one amino acid residue change as compared to a wild type sequence of the Fc domain.
77. The immune-stimulatory conjugate of any one of claims 37 to 38, 39 to 52 and 54 to 76, wherein the Fc domain has at least one amino acid residue change as compared to wildtype, wherein the Fc domain is at comprises at least 80% homologous to SEQ ID NO:
296, and wherein the at least one amino acid residue change is:
a) F243L, R292P, Y300L, L235V, and P396L, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898;
b) 5239D and 1332E, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898; or c) 5298A, E333A, and K334A, wherein numbering of amino acid residues in the Fc domain is relative to SEQ ID NO: 898.
78. The immune-stimulatory conjugate of any one of claims 37 to 38, 39 to 52, and 54 to 76, wherein the Fc domain has at least one amino acid residue change as compared to wildtype, wherein the Fc domain is at comprises at least 80% homologous to SEQ ID NO:
898, and wherein the at least one amino acid residue change is:
a) N297A, N297G, N297Q, N297D as in Kabat numbering and relative to SEQ ID
NO: 898; or b) K322A/L234A/L235A N296A as in Kabat numbering and relative to SEQ ID NO:
898;
or c) L234F/L235E/P331S N296A as in Kabat numbering and relative to SEQ ID NO:
898; or d) P329G/L234A/L235A as in Kabat numbering and relative to SEQ ID NO: 898.
79. The immune-stimulatory conjugate of any one of claims 37 to 78, wherein the molar ratio of immune-stimulatory compound to antibody is less than 5.
80. A pharmaceutical composition comprising the conjugate of any one of claims 37 to 79 and a pharmaceutically acceptable excipient.
81. A method of treating cancer, comprising administering to a subject in need thereof the pharmaceutical composition of claim 80.
82. The use of the conjugate of any one of claims 37 to 79 or the pharmaceutical composition of claims 80 to 81 as a medicament for the treatment of cancer.
CA3065919A 2017-06-07 2018-06-07 Antibody construct conjugates Abandoned CA3065919A1 (en)

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