EA041992B1 - CONSTRUCTION OF A BI-SPECIFIC ANTIBODY AGAINST CD70 AND CD3 - Google Patents

Description

The invention relates to a bispecific antibody construct comprising a first binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell. In addition, the invention provides a polynucleotide encoding an antibody construct, a vector containing said polynucleotide, and a host cell transformed or transfected with said polynucleotide or vector. In addition, the invention provides a method for producing an antibody construct of the invention, a medical application of said antibody construct, and a kit containing said antibody construct.

CD70 (CD27L, TNFSF7) is a type II integral membrane protein whose normal expression is restricted to a subset of activated T and B cells, mature dendritic cells, and thymic medullary epithelial cells. The biological functions of CD70 are mediated by binding to the CD27 receptor, which is expressed on lymphocytes and NK cells. The CD70 interaction regulates B-cell maturation, T-cell co-stimulation, and memory T-cell function. Genetic ablation of CD27 in mice, which abolishes CD70 signaling, does not affect B and T cell development, but interferes with the memory response to repeated exposure to the virus.

In addition to its severely restricted normal expression, aberrant CD70 expression has been reported in 60% of non-Hodgkin's lymphomas (NHL), 70% of clear cell renal cell carcinomas (ccRCCs), 40% of papillary RCCs, as well as 25% of pancreatic adenocarcinomas, 22% of laryngeal carcinomas. /pharynx, 15% ovarian carcinomas and 10% lung adenocarcinomas and glioblastomas.

Every year, 14,080 people die from metastatic RCC in the US (American Cancer Society: Cancer Facts and Figures. 2015). While all patients are treated with angiogenesis inhibitors (bevacizumab, sunitinib, sorafenib, axitinib) or mTOR inhibitors (temsirolimus, everolimus), the 5-year survival rate of patients with metastatic RCC remains extremely low at 20% (American Cancer Society: Cancer Facts and Figures 2015 ). A significant unmet medical need remains for this disease, and in the US up to 10,000 patients per year with CD70-expressing metastatic ccRCC may benefit from CD70-targeting therapy.

Diffuse large B-cell lymphoma (DLBCL) is the largest subtype of NHL, with 28,740 new cases per year in the US. (American Cancer Society: Cancer Facts and Figures, 2015). 71% of DLBCL tumors express CD70, and while most patients initially respond to standard therapies (rituxan plus cyclophosphamide, adriamycin, vincristine, prednisone), many relapse or are resistant, and 19,790 patients die from the disease each year (American Cancer Society : Cancer Facts and Figures 2015). Therefore, there remains a clear unmet medical need for DLBCL, and in the US up to 14,000 patients per year with CD70-expressing DLBCL may benefit from CD70-targeting therapy.

Based on the number of patients dying each year in the US from pancreatic (40,560), laryngeal and pharyngeal (6,300), ovarian (14,180), and lung (158,000) carcinomas (American Cancer Society: Cancer Facts and Figures, 2015), and taking into account Considering the prevalence of CD70 expression in these types of cancer, up to 30,000 additional unmet patients per year with CD70-expressing solid tumors in the US could benefit from CD70-targeted therapy.

As there is still a need for additional options for treating cancers associated with overexpression of CD70, such as those discussed above, this document provides tools and methods to address this problem in the form of a bispecific anti-CD70xCD3 antibody construct.

Thus, in a first aspect, the present invention provides a bispecific antibody construct comprising a first binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell.

It should be noted that the use of singular definitions in this document does not exclude the possibility of plural definitions, unless otherwise expressly stated in the text. Thus, for example, a reference to a reagent includes one or more of these various reagents, and a reference to a method includes a reference to equivalent steps and methods known to those skilled in the art, which may be modified or replaced by the methods described herein.

Unless otherwise indicated, a term at least preceding a series of elements is to be understood as referring to each element of the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be embraced by the present invention.

The term, and/or wherever it is used, includes the meaning of and, or and all or any other combination of the elements associated with the specified term.

As used herein, the term about or approximately means within

- 1 041992 ±20%, preferably within ±15%, more preferably within ±10%, and most preferably within ±5% of the set value or range.

Throughout this specification and the following claims, unless the context otherwise requires, the word contain, and variations such as contains and containing, will be intended to include the specified integer or step or group of integers or steps, but not the exclusion of any other integer. number or step, or a group of integers or steps. As used herein, containing may be replaced by the term including, or sometimes, when used herein, by the term having.

As used herein, the term consisting of excludes any element, step, or ingredient not listed in the claimed element. As used herein, the term consisting essentially of does not exclude materials or steps that do not significantly affect the essential and new characteristics of the application.

In each instance in this document, any of the terms comprising, consisting primarily of, and consisting of may be replaced by any of the other two terms.

The term antibody construct refers to a molecule in which the structure and/or function is(s) based on the structure and/or function of an antibody, eg, a full length or whole immunoglobulin molecule. Thus, an antibody construct is capable of binding to its specific target or antigen. In addition, the design of the antibody in accordance with the invention contains the minimum structural requirements for the antibody, which allow binding to the target. This minimum requirement may, for example, be defined by having at least three light chain CDRs (i.e., VL region CDR1, CDR2, and CDR3) and/or three heavy chain CDRs (i.e., VH region CDR1, CDR2, and CDR3), preferably all six CDRs. Antibodies on which the constructs of the invention are based include, for example, monoclonal, recombinant, chimeric, deimmunized, humanized and human antibodies.

In the definition of antibody constructs in accordance with the invention, full-length or whole antibodies are provided, including also camel antibodies and other immunoglobulin antibodies obtained by biotechnological or protein engineering methods or methods. These full length antibodies can be, for example, monoclonal, recombinant, chimeric, deimmunized, humanized and human antibodies. Also present in the definition of antibody constructs are fragments of full length antibodies such as VH, VHH, VL, (s)dAb, Fv, Fd, Fab, Fab', F(ab')2, or r IgG (half bodies). The antibody constructs of the invention may also be modified antibody fragments, also referred to as antibody variants, such as scFv, di-scFv or bi(s)-scFv, scFv-Fc, scFv-zip, scFab, Fab2, Fab3, diabodies, single chain diabodies, tandem diabodies (Tandab), tandem di-scFv, tandem tri-scFv, minibodies represented by a structure that looks like this: (VH-VL-CH3) ₂ , (scFv-CH3) ₂ , ((scFv) ₂ CH3+CH3), ((scFv) ₂ -CH3) or (scFv-CH3-scFv) ₂ , multibodies such as triabodies or tetrabodies, and single domain antibodies such as nanobodies or single variable domain antibodies containing only one variable domain , which may be a VHH, VH, or VL that specifically binds an antigen or epitope, regardless of other V regions or domains. Other preferred formats for constructs of antibodies in accordance with the invention are crossbody, maxibody, hetero-Fc constructs and moho-Fc constructs. Examples of these formats will be described below.

The binding domain may typically comprise an antibody light chain variable region (VL) and an antibody heavy chain variable region (VH); however, it must not contain both areas. Fd fragments, for example, have two VH regions and often retain some of the antigen-binding function of an intact antigen-binding domain. Additional examples for the format of antibody fragments, antibody variants, or binding domains include (1) a Fab fragment, a monovalent fragment having VL, VH, CL, and CH1 domains; (2) an F(ab')2 fragment, a divalent fragment having two Fab fragments connected by a disulfide bridge at the hinge region; (3) an Fd fragment having two VH and CH1 domains; (4) an Fv fragment having VL and VH domains of one antibody arm, (5) a dAb fragment (Ward et al., (1989) Nature 341: 544-546) which has a VH domain; (6) an isolated complementarity determination region (CDR); and (7) a single chain Fv (scFv), the latter being preferred (eg, derived from an scFv library). Examples of embodiments of antibody constructs according to the invention are, for example, those described in WO 00/006605, WO 2005/040220, WO 2008/119567, WO 2010/037838, WO 2013/026837, WO 2013/026833, US 2014/0308285, US 2014/0302037, WO2014/144722, WO 2014/151910 and WO 2015/048272.

In addition, the definition of the term antibody construct includes monovalent, divalent, and polyvalent/multivalent constructs, and thus monospecific constructs that specifically bind to only one antigenic structure, as well as bispecific and polyspecific/multispecific constructs that specifically bind more than one antigenic structure, for example two, three or more, through different binding domains. In addition, the definition of the term antibody construct includes molecules consisting of only one

- 2 041992 polypeptide chain, as well as molecules consisting of more than one polypeptide chain, and the chains can be either identical (homodimers, homotrimers or homogeneous oligomers) or different (heterodimer, heterotrimer or heterooligomer). Examples of the above antibodies and variants or derivatives thereof are described in particular in Harlow and Lane, Antibodies a laboratory manual, CSHL Press (1988) and Using Antibodies: a laboratory manual, CSHL Press (1999), Kontermann and Dubel, Antibody Engineering, Springer, 2nd ed. 2010 and Little, Recombinant Antibodies for Immunotherapy, Cambridge University Press 2009.

The antibody constructs of this invention are preferably in vitro antibody constructs. This term refers to an antibody construct as defined above, in which all or part of the variable region (e.g., at least one CDR) is generated in non-immune cell selection, e.g., in vitro phage display, protein chip, or any other method, wherein candidate sequences can be tested for their ability to bind to an antigen. Thus, the term preferably excludes sequences generated solely by genomic rearrangement in an animal's immune cell. A recombinant antibody is an antibody obtained using recombinant DNA technology or genetic engineering.

The term monoclonal antibody (mAb) or monoclonal antibody construct as used herein refers to an antibody derived from a population of substantially homogeneous antibodies, i.e. the individual antibodies containing the population are identical except for possible natural mutations and/(e.g., isomerization, amidation), which may be present in small amounts. Monoclonal antibodies are highly specific when directed against a single antigenic site or determinant on an antigen, in contrast to conventional (polyclonal) antibodies, which typically include different antibodies directed against different determinants (or epitopes). In addition to their specificity, monoclonal antibodies have the advantage that they are synthesized by hybridoma culture and therefore are not contaminated with other immunoglobulins. The modifier monoclonal indicates the nature of the antibody, which is obtained from a substantially homogeneous population of antibodies, and should not be construed as requiring the production of antibodies in any particular way.

To obtain monoclonal antibodies, you can use any technique that provides antibodies obtained by continuous cultures of cell lines. For example, the monoclonal antibodies to be used can be made using the hybridoma method described above by Koehler et al., Nature, 256:495 (1975), or can be made using recombinant DNA methods (see, for example, US Pat. No. 4816567). Examples of additional methods for generating human monoclonal antibodies include trioma techniques, human B cell hybridoma techniques (Kozbor, Immunology Today 4 (1983), 72), and EBV hybridoma techniques (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985), 77-96).

Hybridomas are then screened using standard methods such as enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (BIACORE™) to identify one or more hybridomas that produce an antibody that specifically binds to said antigen. As an immunogen, you can use any form of the corresponding antigen, such as recombinant antigen, natural forms, any of its variants or fragments, as well as their antigenic peptide. Surface plasmon resonance used in the BIAcore system can be used to increase the efficiency of phage antibodies that bind to a target antigen epitope such as CD70 or CD3 epsilon (Schier, Human Antibodies Hybridomas 7 (1996), 97-105; Malmborg, J. Immunol Methods 183 (1995), 7-13).

Another exemplary method for preparing monoclonal antibodies involves protein expression screening libraries, such as phage display or ribosome display libraries. Phage display is described, for example, in Ladner et al., US patent No. 5223409; Smith (1985) Science 228:1315-1317, Clackson et al., Nature, 352: 624-628 (1991) and Marks et al., J. Mol. Biol., 222: 581-597 (1991).

In addition to using display libraries, an appropriate antigen can be used to immunize a non-human animal, such as a rodent (such as a mouse, hamster, rabbit, or rat). In one embodiment, the non-human animal contains at least a portion of the human immunoglobulin gene. For example, mouse strains deficient in the production of mouse antibodies can be engineered with large fragments of human Ig (immunoglobulin) loci. Using hybridoma technology, it is possible to produce and select antigen-specific monoclonal antibodies derived from genes with the desired specificity. See, for example, XENOMOUSE™, Green et al. (1994) Nature Genetics 7:13-21, US 2003-0070185, WO 96/34096 and WO 96/33735.

The monoclonal antibody can also be obtained from a non-human animal and then modified, eg, humanized, deimmunized, chimerized, etc., using recombinant DNA techniques known in the art. Examples

- 3,041,992 modified antibody constructs include humanized variants of non-human antibodies, affinity matured antibodies (see, e.g., Hawkins et al. J. Mol. Biol. 254, 889-896 (1992) and Lowman et al., Biochemistry 30, 10832 - 10837 (1991)) and mutant antibodies with altered effector function(s) (see, for example, US Pat. No. 5,648,260, Kontermann and Dubel (2010), loc. cit. and Little (2009), loc. cit.).

In immunology, affinity maturation is the process by which B cells produce antibodies with increased affinity for an antigen during an immune response. Upon repeated exposure to the same antigen, the host will produce antibodies with consistently higher affinity. Like the natural prototype, in vitro affinity maturation is based on the principles of mutation and selection. In vitro affinity maturation has been successfully used to optimize antibodies, antibody constructs, and antibody fragments. Random mutations within the CDR are introduced using radiation, chemical mutagens, or error-correcting PCR. In addition, genetic diversity can be increased by strand shuffling. Two or three rounds of mutation and selection using display techniques such as phage display typically results in antibody fragments with affinities in the low nanomolar region.

A preferred type of amino acid substitution variant for antibody constructs involves substitution of one or more hypervariable region residues of the parent antibody (eg, a humanized or human antibody). Typically, the resulting variant(s) selected for further modification will have improved biological properties relative to the original antibody from which they are derived. A suitable method for obtaining such substitution variants involves affinity maturation using phage display. Briefly, several sites of the hypervariable region (eg, 6-7 sites) are subjected to mutagenesis to obtain all possible amino acid substitutions at each site. The antibody variants thus obtained are then detected in monovalent form on the surface of the filamentous bacteriophage particles in the form of their fusion with the M13 bacteriophage gene III product packaged in each particle. The phage display variants are then screened for their biological activity (eg, binding affinity) as described herein. In order to identify possible sites for modification of the hypervariable regions, alanine-scanning mutagenesis can be performed to identify hypervariable region residues that provide significant antigen binding. Alternatively or additionally, it may be useful to analyze the crystal structure of the antigen-antibody complex in order to identify points of contact between the binding domain and, for example, human CD70. Such contacting residues and neighboring residues are potential targets for replacement, according to the methods presented in this document. Once such variants have been generated, they are screened as described herein, and improved antibodies, as established in one or more relevant studies, are selected for further modification.

The monoclonal antibodies and antibody constructs of this invention specifically include chimeric antibodies (immunoglobulins) in which the heavy and/or light chain region is identical or homologous to the corresponding sequences of antibodies derived from a particular species or belonging to a particular class or subclass of antibodies, while the remainder of the chain ( chains) is identical or homologous to the corresponding sequences of antibodies derived from another species or belonging to another class or subclass of antibodies, as well as fragments of such antibodies, provided that they exhibit the desired biological activity (US Patent No. 4816567; Morrison et al., Proc. Natl Acad. Sci. USA, 81: 6851-6855 (1984)). Chimeric antibodies contemplated herein include primatized antibodies containing antigen-binding variable domain sequences derived from a non-human primate antibody (eg, marmosets, great apes, etc.) and human constant region sequences. Various approaches to the creation of chimeric antibodies have been described. See, for example, Morrison et al., Proc. Natl. Acad. ScL U.S.A. 81:6851, 1985; Takeda et al., Nature 314:452, 1985, Cabilly et al., US Pat. No. 4,816,567; Boss et al., US patent No. 4816397; Tanaguchi et al., EP 0171496; EP 0173494 and GB 2177096.

An antibody, antibody construct, antibody fragment, or antibody variant can also be modified by specific deletion of human T cell epitopes (a technique referred to as deimmunization) by the methods described, for example, in WO 98/52976 or WO 00/34317. Briefly, the variable regions of the heavy and light chains of an antibody can be analyzed for peptides that bind to MHC (major histocompatibility complex) class II; these peptides are potential T cell epitopes (as defined in WO 98/52976 and WO 00/34317). A computer modeling approach called peptide threading can be applied to discover potential T-cell epitopes, and in addition the database of human MHC class II binding peptides can be examined for motifs present in VH and VL sequences as described in WO 98/52976 and WO 00/34317. These motifs bind to any of the 18 major MHC class II DR allotypes and thus constitute potential T cell epitopes. Identified potential T-cell epitopes can be eliminated by replacing a small number of amino acids

- 4,041,992 residues in variable domains, or preferably single amino acid substitutions. Usually, conservative substitutions are made. Often, but not exclusively, an amino acid common to a position in human germline antibody sequences can be used. Human germline sequences are disclosed in, for example, Tomlinson, et al. (1992) J. Mol. Biol. 227:776-798; Cook, G.P. et al. (1995) Immunol. Today Vol. 16(5): 237-242 and Tomlinson et al. (1995) EMBO J. 14:14:4628-4638. The VBASE catalog is a complete catalog of human immunoglobulin variable region sequences (compiled by Tomlinson LA et al., MRC Protein Modification Center, Cambridge, UK). These sequences can be used as a source of human sequence, for example for frameworks and CDRs. Human consensus framework regions can also be used, for example, as described in US Pat. No. 6,300,064.

Humanized antibodies, antibody constructs, variants or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding antibody subsequences) are antibodies or immunoglobulins, mostly human sequences, that contain (a) minimal sequence (i) derived from non-human immunoglobulin. In most cases, humanized antibodies are human (recipient antibody) immunoglobulins in which residues from the hypervariable region (also CDR) of the recipient are replaced by residues from the hypervariable region (donor antibody) of a non-human species (e.g., rodents), such as, mouse, rat, hamster or rabbit having the desired specificity, affinity and potency. In some instances, Fv framework region (FR) residues of a human immunoglobulin are replaced with corresponding non-human residues. In addition, the humanized antibodies used herein may also contain residues that are not found in either the recipient antibody or the donor antibody. These modifications are made to further purify and optimize antibody performance. The humanized antibody may also comprise at least an immunoglobulin constant region (Fc) fragment, typically derived from a human immunoglobulin. For additional information, see Jones et al., Nature, 321: 522-525 (1986); Reichmann et al., Nature, 332: 323-329 (1988) and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992).

Humanized antibodies or fragments thereof can be generated by substituting Fv variable domain sequences that are not directly linked to antigen binding with equivalent sequences from human Fv variable domains. Exemplary methods for preparing humanized antibodies or fragments thereof are provided by Morrison (1985) Science 229:1202-1207; Oi et al. (1986) BioTechniques 4:214 and US 5,585,089; US 5693761; US 5693762; US 5,859,205 and US 6,407,213. These methods include the isolation, manipulation and expression of nucleic acid sequences that encode all or part of the Fv variable domains of an immunoglobulin from at least one heavy or light chain. Such nucleic acids can be obtained from a hybridoma producing an antibody against a given target, as described above, as well as from other sources. The recombinant DNA encoding the humanized antibody can then be cloned into an appropriate expression vector.

Humanized antibodies can also be generated using transgenic animals such as mice that express human heavy and light chain genes but are unable to express endogenous mouse immunoglobulin heavy and light chain genes. Winter describes an exemplary CDR grafting method that can be used to prepare the humanized antibodies described herein (US Pat. No. 5,225,539). All of the CDRs of a particular human antibody may be replaced with at least a portion of a non-human CDR, or only some of the CDRs may be replaced with non-human CDRs. It is only necessary to change the number of CDRs needed to bind a humanized antibody to a given antigen.

A humanized antibody can be optimized by introducing conservative substitutions, consensus sequence substitutions, germline substitutions, and/or back mutations. Such altered immunoglobulin molecules can be prepared by any of several methods known in the art (e.g., Teng et al., Proc. Natl. Acad. Sci. U.S.A., 80: 73087312, 1983; Kozbor et al., Immunology Today, 4 : 7279, 1983; Olsson et al., Meth. Enzymol., 92: 3-16, 1982 and EP 239400).

The term human antibody, human antibody construct, and human binding domain includes antibodies, antibody constructs, and binding domains having antibody regions, such as variable and constant regions or domains, that substantially correspond to human germline immunoglobulin sequences known in the art, including, for example, those described by Kabat et al. (1991) (loc. cit.). Human antibodies, antibody constructs, or binding domains of the invention may contain amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by in vitro random or site-directed mutagenesis or by in vivo somatic mutation), for example, in CDRs and , in particular, in CDR3. Human antibodies, antibody constructs, or binding domains may have at least one, two, three, four, five, or more positions,

- 5,041,992 containing an amino acid residue that is not encoded by a human germline immunoglobulin sequence. The definition of human antibodies, antibody constructs, and binding domains used herein also contemplates fully human antibodies that contain only non-artificial and/or genetically altered human antibody sequences as they can be generated using technologies or systems such as Xenomouse.

In some embodiments, the antibody constructs of the invention are isolated or substantially pure antibody constructs. Isolated or substantially pure, when used to describe an antibody construct disclosed herein, means an antibody construct that has been identified, separated, and/or isolated from a component of its production environment. Preferably, the antibody construct is free or substantially unrelated to all other components from its production environment. Contaminant components from its natural environment, such as those derived from recombinant transfected cells, are materials that may interfere with diagnostic or therapeutic applications of the polypeptide and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. The antibody constructs may comprise, for example, at least about 5% or at least about 50% of the total protein in a given sample. It is understood that the isolated protein may comprise from 5 to 99.9 wt.% of the total protein content, depending on the circumstances. The polypeptide can be produced at a significantly higher concentration by using an inducible promoter or a highly expressed promoter such that it is produced at higher concentrations. The definition includes the generation of an antibody construct in a wide variety of organisms and/or host cells that are known in the art. In preferred embodiments, the antibody construct will be purified (1) to a degree sufficient to obtain at least 15 residues on the N-terminal or internal amino acid sequence by using a rotating cup sequencer or (2) to homogeneity obtained by SDS-PAGE electrophoresis in non-reducing or reducing conditions using Coomassie blue or, preferably, silver staining. In this case, as a rule, the isolated antibody construct is obtained using at least one purification step.

The term binding domain characterizes in connection with the present invention a domain that (in particular) binds to/interacts with/recognizes a given target epitope or a given target site on target molecules (antigens), herein CD70 and CD3, respectively. The structure and function of the first binding domain (recognizing CD70) and preferably also the structure and/or function of the second binding domain (recognizing CD3) are/are based on the structure and/or function of an antibody, eg a full length or whole immunoglobulin molecule. According to the invention, the first binding domain is characterized by having three light chain CDRs (ie CDR1, CDR2 and CDR3 of the VL region) and/or three CDRs of the heavy chain (ie CDR1, CDR2 and CDR3 of the VH region). The second binding domain preferably also contains the minimum structural requirements for the antibody, which allow binding to the target. More preferably, the second binding domain contains at least three light chain CDRs (ie CDR1, CDR2 and CDR3 of the VL region) and/or three CDRs of the heavy chain (ie CDR1, CDR2 and CDR3 of the VH region). It is contemplated that the first and/or second binding domain is or is generated by phage display or library screening methods and not by substitution of CDR sequences from a pre-existing (monoclonal) antibody into a scaffold.

In accordance with the present invention, binding domains are in the form of one or more polypeptides. Such polypeptides may include proteinaceous portions and non-proteinaceous portions (eg, chemical linkers or chemical crosslinkers such as glutaraldehyde). Proteins (including their fragments, preferably biologically active fragments and peptides, usually having less than 30 amino acids) contain two or more amino acids linked to each other through a covalent peptide bond (to form an amino acid chain). As used herein, the term polypeptide describes a group of molecules that typically consist of more than 30 amino acids. The polypeptides may further form multimers such as dimers, trimers and higher oligomers, ie consisting of more than one polypeptide molecule. The polypeptide molecules forming such dimers, trimers, etc. may be identical or non-identical. The corresponding higher order structures of such multimers are therefore called homo- or heterodimers, homo- or heterotrimers, etc. An example for this heterocyclim is an antibody molecule, which in its natural form consists of two identical light polypeptide chains and two identical heavy polypeptide chains. The terms peptide, polypeptide and protein also refer to naturally modified peptides/polypeptides/proteins in which the modification is carried out, for example, by post-translational modifications such as glycosylation, acetylation, phosphorylation and the like. The peptide, polypeptide or protein referred to herein may also be chemically modified, such as pegylated. Such modifications are well known in the art and are described below.

Preferably, the binding domain that binds to CD70 and/or the binding domain that binds to CD3 is/are human binding domains. Antibodies and antibody constructs containing at least one human binding domain avoid some of the problems associated with antibodies or antibody constructs that have non-human derived variable and/or constant regions, such as rodent (e.g., mouse, rat , hamster or rabbit). The presence of such rodent-derived proteins may result in rapid clearance of the antibody or antibody construct, or may result in an immune response against the antibody or antibody construct by the patient. To avoid the use of rodent-derived antibodies or antibody constructs, fully human antibodies or antibody constructs can be made by introducing a human antibody function into the rodent such that the rodent produces fully human antibodies.

The ability to clone and regenerate human loci thousands of bases (megabases) in YAC and introduce them into the mouse germline provides a powerful approach to elucidating the functional components of very large or roughly mapped loci, as well as generating useful human disease models. In addition, the use of such technology to replace mouse loci with their human equivalents could provide unique insights into the expression and regulation of human gene products during development, their relationship to other systems, and their involvement in disease induction and progression.

An important practical application of such a strategy is the humanization of the mouse humoral immune system. The introduction of human immunoglobulin (Ig) loci into mice with inactivated endogenous Ig genes provides an opportunity to study the mechanisms underlying the programmed expression and assembly of antibodies, as well as their role in the development of B cells. Moreover, such a strategy could be an ideal source for the production of fully human monoclonal antibodies (mAbs) - an important milestone in achieving promising antibody therapy in human diseases. Fully human antibodies or antibody constructs are expected to minimize the immunogenic and allergic reactions inherent in murine or mouse-derived monoclonal antibodies and thus improve the efficacy and safety of administered antibodies/antibody constructs. The use of fully human antibodies or antibody constructs can be expected to be a significant advantage in the treatment of chronic and recurrent human diseases such as inflammation, autoimmune diseases and cancer, which require repeated complex administrations.

One approach to this goal has been to construct mouse strains deficient in the production of mouse antibodies with large fragments of human Ig loci in the expectation that such mice will produce a large repertoire of human antibodies in the absence of mouse antibodies. Large fragments of human Ig retain a wide variety of variable genes, as well as the correct regulation of antibody production and expression. By using a murine mechanism to diversify and select antibodies and eliminate immunological tolerance to human proteins, the reproducible human antibody repertoire in these mouse strains should produce antibodies with high affinity for any antigen of interest, including human antigens. Using hybridoma technology, antigen-specific human mAbs with the desired specificity can be easily generated and selected. This general strategy has been demonstrated in connection with the production of the first strains of XenoMouse mice (see Green et al. Nature Genetics 7:13-21 (1994)). XenoMouse strains were constructed using yeast artificial chromosomes (YACs) containing 245 kb and 190 kb germline configuration fragments of the human heavy chain locus and the kappa light chain locus, respectively, which contained variable and constant region core sequences. Human Ig containing YAC was found to be compatible with the mouse system for both rearrangement and antibody expression and was able to replace inactivated mouse Ig genes. This has been demonstrated by their ability to induce B cell development, produce an adult-like human repertoire of fully human antibodies, and generate antigen-specific human mAbs. These results also suggested that the introduction of large portions of human Ig loci containing more V genes, additional regulatory elements and human Ig constant regions could largely reproduce the full repertoire characteristic of the human humoral response to infection and immunization. The work of Green et al. has recently been expanded to include more than about 80% of the human antibody repertoire by introducing megabase size YAC fragments with the germline configuration of human heavy chain loci and kappa light chain loci, respectively. See Mendez et al. Nature Genetics 15:146-156 (1997) and US Patent Application No. 08/759620.

The production of XenoMouse mice is further discussed and characterized in US Patent Applications No.

07/466008, #07/610515, #07/919297, #07/922649, #08/031801, #08/112848, #08/234145, #

08/376279, #08/430938, #08/464584, #08/464582, #08/463191, #08/462837, #08/486853, #

08/486857, No. 08/486859, No. 08/462513, No. 08/724752 and No. 08/759620, and US patent No. 6162963;

6150584; 6114598; 6075181, and 5939598 and Japanese Patent No. 3068180 B2, 3068506 B2 and 3068507 B2. Cm.

- 7 041992 also Mendez et al. Nature Genetics 15:146-156 (1997) and Green and Jakobovits J. Exp. Med. 188:483-495 (1998), EP 0463151 B1, WO 94/02602, WO 96/34096, WO 98/24893, WO 00/76310 and WO 03/47336.

In an alternative approach, others, including GenPharm International, Inc., have used the minilocus approach. In the minilocus approach, an exogenous Ig locus is mimicked by incorporating pieces (individual genes) from the Ig locus. Thus, one or more VH genes, one or more DH genes, one or more JH genes, a mu constant region, and a second constant region (preferably a gamma constant region) are combined into a construct for administration to an animal. This approach is described in US Pat. No. 5,545,807 to Surani et al. and US Pat. No. 5,545,806; 5625825; 5625126; 5633425; 5661016; 5770429; 5789650; 5814318; 5877397; 5,874,299 and 6,255,458 each Lonberg and Kay US Pat. Nos. 5,591,669 and 6,023,010 Krimpenfort and Berns US Pat. 5721367; and 5,789,215 Berns et al. and U.S. Patent No. 5,643,763 Choi and Dunn, and GenPharm International U.S. Patent Application No. 07/574748, No. 07/575962, No. 07/810279, No. 07/853408, No. 07/904068, No. 07 /990860, No. 08/053131, No. 08/096762, No. 08/155301, No. 08/161739, No. 08/165699, No. 08/209741. See also EP 0546073 B1, WO 92/03918, WO 92/22645, WO 92/22647, WO 92/22670, WO 93/12227, WO 94/00569, WO 94/25585, WO 96/14436, WO 97/ 13852 and WO 98/24884 and US Pat. No. 5,981,175. See also Taylor et al. (1992), Chen et al. (1993), Tuaillon et al. (1993), Choi et al. (1993), Lonberg et al. (1994), Taylor et al. (1994), and Tuaillon et al. (1995), Fishwild et al. (1996).

Kirin has also demonstrated the formation of human antibodies in mice in which large fragments of chromosomes or entire chromosomes have been introduced through microcell fusion. See European Patent Applications Nos. 773288 and 843961. Xenerex Biosciences is developing technology for the potential generation of human antibodies. In this technology, SCID mice are reconstituted with human lymphatic cells, such as B and/or T cells. Mice are then immunized with antigen and can elicit an immune response against the antigen. See US Pat. No. 5,476,996; 5698767 and 5958765.

Human anti-mouse antibody (HAMA) reactions have led the industry to prepare chimeric or otherwise humanized antibodies. However, it is expected that some human responses against the chimeric antibody (HACA) will be observed, especially when using chronic or multi-dose use of the antibody. Thus, it would be desirable to provide antibody constructs containing a human anti-CD70 binding domain and/or a human anti-CD3 binding domain to enhance the effects and/or responses of HAMA or HACA.

The CD70 binding domains of the bispecific antibody constructs that were obtained in the context of this invention were characterized by their epitope specificity as described in Example 2. The binding domains were classified into different groups (I, II, III, IIIv, V, VI, VII and VIII - see Table 4), depending on the chimeric CD70 molecule for which binding loss was observed in flow cytometric readings. Therefore, according to a preferred embodiment, the first binding domain of the antibody construct of the invention binds to the CD70 epitope which is in the region indicated by E3 (region represented in SEQ ID NO: 745). As described below, the E3 recognition region of the binding domain can recognize additional regions of CD70.

In addition, the first binding domain of an antibody construct of the invention is contemplated to bind to a CD70 epitope that contains combinations of CD70 regions selected from the group consisting of:

a) areas E2, E3, E4 and E6,

b) areas E2, E3 and E4,

c) areas E2, E3 and E6,

d) areas E2 and E3,

e) areas E3, E4 and E6,

f) areas E3 and E4, and

g) areas E3 and E6,

The epitope recognized by the anti-CD70 binding domain may be linear or conformational. The position of the above-described regions E2, E3, E4 and E6 in the human CD70 protein, as well as their sequence identifiers, are described in Example 1.

In yet another preferred embodiment, the first binding domain of the antibody construct of the invention does not bind to an epitope contained in the region labeled E1. Additionally or alternatively, it is contemplated that the first binding domain of the antibody construct of the invention does not bind to an epitope contained in the region labeled E7.

The terms (specifically) binds to, (specifically) recognizes, (specifically) targets, and (specifically) reacts with means in accordance with the present invention that the binding domain interacts or specifically interacts with a given epitope or a given target site on target molecules ( antigen), in this document: CD70 and CD3, respectively.

The term epitope refers to a site on an antigen to which a binding domain, antibody, or immunoglobulin, or derivative, or fragment, or variant of an antibody or immunoglobulin specifically binds. An epitope is antigenic and therefore the term epitope is sometimes also referred to

- 8 041992 in this document as an antigenic structure or antigenic determinant. Thus, the binding domain is the interaction site for the antigen. Said binding/interaction is also understood as specific recognition.

Epitopes can be formed by both adjacent amino acids and non-adjacent amino acids that converge as a result of protein folding into a tertiary structure. A linear epitope is an epitope in which the primary amino acid sequence contains a recognized epitope. A linear epitope usually contains at least 3 or at least 4 and more usually at least 5 or at least 6 or at least 7, for example 8 to 10 amino acids in a unique sequence.

A conformational epitope, as opposed to a linear epitope, is an epitope in which the primary amino acid sequence containing the epitope is not the only defining component of the recognized epitope (eg, an epitope in which the primary amino acid sequence is not necessarily recognized by the binding domain). Typically, the conformational epitope contains an increased number of amino acids relative to the linear epitope. With regard to the recognition of conformational epitopes, the binding domain recognizes the three-dimensional structure of an antigen, preferably a peptide or protein or fragment thereof (in the context of this invention, the antigenic structure for the first binding domain is within CD70). For example, when a protein molecule is folded to form a three-dimensional structure, certain amino acids and/or the polypeptide backbone that form the conformational epitope become matched, allowing the antibody to recognize the epitope. Methods for determining the conformation of epitopes include, but are not limited to, X-ray diffraction crystallography, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR), and site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy.

The epitope mapping method is described as follows: When a region (contiguous consecutive amino acids) in the human CD70 protein is replaced/replaced by a corresponding region of a non-human or non-primate CD70 antigen (e.g. mouse CD70, but others such as chicken, rat, hamster) , rabbit, etc. may also be suitable), there may be a decrease in binding domain binding, unless the binding domain is cross-specific for the non-human and non-primate CD70 used. Said reduction is preferably at least 10%, 20%, 30%, 40%, 50%, more preferably at least 60%, 70% or 80%, most preferably 90%, 95% or even 100% compared to the binding of the corresponding region of the human CD70 protein, wherein binding to the corresponding region in the human CD70 protein is set to 100%. The aforementioned CD70/non-human CD70 chimeras are expected to be expressed in CHO cells. It is also assumed that the v5 label is fused at the C-terminus of the chimeric molecules, for example, through a GGGGS linker. The method is described in more detail in examples 1 and 2.

In an alternative or additional epitope mapping method, multiple truncated versions of the human CD70 extracellular domain can be generated to determine the specific region that is recognized by the binding domain. In these truncated versions, the various extracellular domains/subdomains or regions of CD70 are removed in stages starting from the C-terminus. Truncated versions of CD70 are believed to be expressed in CHO cells. It is also assumed that the v5 label is fused at the C-terminus of the truncated molecules, for example, through the GGGGS linker, which allows checking their correct expression on the cell surface. It is expected that there will be a reduction or loss of binding to these truncated versions of CD70 that no longer cover the region of CD70 that is recognized by the binding domain. The binding reduction is preferably at least 10%, 20%, 30%, 40%, 50%; more preferably at least 60%, 70%, 80%, and most preferably 90%, 95%, or even 100%, with binding to the entire human CD70 protein (or its extracellular region or domain) set to 100%.

Another way to determine the contribution of a particular target antigen residue to recognition by an antibody construct or binding domain is an alanine scan (see, e.g., Morrison KL & Weiss GA. Cur Opin Chem Biol. 2001 Jun;5(3):302-7 ), in which each residue to be analyzed is replaced by alanine, i.e. through site-directed mutagenesis. Alanine is used because of its small volume, chemically inert, functional group, which nevertheless mimics the secondary structure traits that many other amino acids have. Sometimes large amino acids such as valine or leucine can be used in cases where it is desirable to maintain the size of the mutated residues. Alanine scanning is not a new technology that has been used for a long period of time.

The interaction between the binding domain and the epitope or region containing the epitope implies that the binding domain exhibits a marked affinity for the epitope/region containing the epitope on a particular protein or antigen (in this case: CD70 and CD3, respectively) and, as a rule, does not have a significant reactivity with proteins or antigens other than CD70 or CD3. Marked affinity includes binding with an affinity of about 10 ^-6 M (KD) or greater. Preferably, binding is considered specific when the binding affinity is between 10 ^-12

- 9 041992 to 10 ^-8 M, from 10 ^-12 to 10 ^-9 M, from 10 ^-12 to 10 ^-10 M, from 10 ^-11 to 10 ^-8 M, preferably from 10 ^-11 to 10 ^-9 M.

Regardless of whether a binding domain specifically reacts with or binds to a target, one can specifically compare the reaction of said binding domain with a target protein or antigen with the reaction of said binding domain with proteins or antigens other than CD70 or CD3. Preferably, the binding domain of the invention does not substantially or substantially bind to proteins or antigens other than CD70 or CD3 (i.e. the first binding domain is unable to bind to proteins other than CD70 and the second binding domain is unable to bind to proteins , other than CD3).

The term does not substantially bind or is unable to bind means that the binding domain of the invention does not bind a protein or antigen other than CD70 or CD3, i.e. does not show a reactivity of more than 30%, preferably no more than 20%, more preferably no more than 10% , particularly preferably not more than 9%, 8%, 7%, 6% or 5% with proteins or antigens other than CD70 or CD3, with binding to CD70 or CD3 respectively set to 100%.

Specific binding is believed to be mediated by specific motifs in the amino acid sequence of the binding domain and antigen. Thus, binding is achieved as a result of their primary, secondary and/or tertiary structure, as well as secondary modifications of these structures. The specific interaction of an interaction site of an antigen with its specific antigen may result in a simple binding of said site to the antigen. Moreover, the specific interaction of an antigen's interaction site with its specific antigen may alternatively or additionally lead to signal initiation, e.g., due to the induction of a conformational change in the antigen, oligomerization of the antigen, etc.

Preferably, the first binding domain of the bispecific antibody construct of the invention comprises a VH region containing CDR-H1, CDR-H2 and CDR-H3 and a VL region containing CDR-Ll, CDR-L2 and CDR-L3, in which CDR-H1, CDR -H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are selected from the group consisting of the groups shown in:

1) SEQ id : NO: 1-6; 37) SEQ ID NO: 361-366; 2) SEQ id : NO: 11-16; 38) SEQ ID NO: 371-376; 3) SEQ id : NO: 21-26; 39) SEQ ID NO: 381-386; 4) SEQ id : NO: 31-36; 40) SEQ ID NO: 391-396; 5) SEQ id : NO: 41-46; 41) SEQ ID NO: 401-406; 6) SEQ id : NO: 51-56; 42) SEQ ID NO: 411-416; 7) SEQ id : NO: 61-66; 43) SEQ ID NO: 421-426; 8) SEQ id : NO: 71-76; 44) SEQ ID NO: 431-436; 9) SEQ id : NO: 81-86; 45) SEQ ID NO: 441-446; 10) SEQ ID NO: : 91-96; 46) SEQ ID NO: 451-456; eleven) SEQ ID NO: : 101-106; 47) SEQ ID NO: 461-466; 12) SEQ ID NO: : 111-116; 48) SEQ ID NO: 471-476; 13) SEQ ID NO: : 121-126; 49) SEQ ID NO: 481-486; 14) SEQ ID NO: : 131-136; 50) SEQ ID NO: 491-496; 15) SEQ ID NO: : 141-146; 51) SEQ ID NO: 501-506; 16) SEQ ID NO: 151-156; 52) SEQ ID NO: 511-516; 17) SEQ ID NO: 161-166; 53) SEQ ID NO: 521-526; 18) SEQ ID NO: 171-176; 54) SEQ ID NO: 531-536; 19) SEQ ID NO: 181-186; 55) SEQ ID NO: 541-546; 20) SEQ ID NO: 191-196; 56) SEQ ID NO: 551-556; 21) SEQ ID NO: 201-206; 57) SEQ ID NO: 561-566; 22) SEQ ID NO: 211-216; 58) SEQ ID NO: 571-576; 23) SEQ ID NO: 221-226; 59) SEQ ID NO: 581-586; 24) SEQ ID NO: 231-236; 60) SEQ ID NO: 591-596;

- 10 041992

25) SEQ ID NO: 241-246; 61) SEQ ID NO: 601-606; 26) SEQ ID NO: 251-256; 62) SEQ ID NO: 611-616; 27) SEQ ID NO: 261-266; 63) SEQ ID NO: 621-626; 28) SEQ ID NO: 271-276; 64) SEQ ID NO: 631-636; 29) SEQ ID NO: 281-286; 65) SEQ ID NO: 641-646; thirty) SEQ ID NO: 291-296; 66) SEQ ID NO: 651-656; 31) SEQ ID NO: 301-306; 67) SEQ ID NO: 661-666; 32) SEQ ID NO: 311-316; 68) SEQ ID NO: 671-676; 33) SEQ ID NO: 321-326; 69) SEQID NO: 681-686; 34) SEQ ID NO: 331-336; 70) SEQ ID NO: 691-696; 35) SEQ ID NO: 341-346; 71) SEQ ID NO: 701-706; 36) SEQ ID NO: 351-356; 72) SEQ ID NO: 711-716; 73) SEQ ID NO: 721-726; 94) SEQ ID NO: 1310-1315; 74) SEQ ID NO: 731-736; 95) SEQ ID NO: 1324-1329; 75) SEQ ID NO: 1044-1049; 96) SEQ ID NO: 1338-1343; 76) SEQ ID NO: 1058-1063; 97) SEQ ID NO: 1352-1357; 77) SEQ ID NO: 1072-1077; 98) SEQ ID NO: 1366-1371; 78) SEQ ID NO: 1086-1091; 99) SEQ ID NO: 1380-1385; 79) SEQ ID NO: 1100-1005; 100) SEQ ID NO: 1394-1399; 80) SEQ ID NO: 1114-1119; 101) SEQID NO: 1408-1413; 81) SEQ ID NO: 1128-1133; 102) SEQID NO: 1422-1427; 82) SEQ ID NO: 1142-1147; 103) SEQID NO: 1436-1441; 83) SEQ ID NO: 1156-1161; 104) SEQID NO: 1450-1455; 84) SEQ ID NO: 1170-1175; 105) SEQID NO: 1464-1469; 85) SEQ ID NO: 1184-1189; 106) SEQID NO: 1478-1483; 86) SEQ ID NO: 1198-1203; 107) SEQID NO: 1492-1497; 87) SEQ ID NO: 1212-1217; 108) SEQID NO: 1506-1511; 88) SEQ ID NO: 1226-1231; 109) SEQID NO: : 1520-1525; 89) SEQ ID NO: 1240-1245; 110) SEQ ID NO: : 1534-1539; 90) SEQ ID NO: 1254-1259; 111) SEQ ID NO: : 1548-1553; And 91) SEQ ID NO: 1268-1273; 112) SEQ ID NO: : 1562-1567. 92) SEQ ID NO: 1282-1287; 93) SEQ ID NO: 1296-1301;

From the above antibody constructs, it was found that the following useful properties were obtained as defined in Examples 3-16: A bispecific antibody construct comprising a first binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that human CD3 on the surface of a T cell, wherein the first binding domain comprises a VH region containing CDR-H1, CDR-H2 and CDR-H3 and a VL region containing CDR-L1, CDR-L2 and CDR-L3, wherein said CDRs are H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are selected from the group consisting of those listed in:

- 11 041992

1) SEQ ID NO: 1044-1049; 2) SEQ ID NO: 1086-1091; 3) SEQ ID NO: 1142-1147; 4) SEQ ID NO: 1170-1175; 5) SEQ ID NO: 1184-1189; 6) SEQ ID NO: 1212-1217; 7) SEQ ID NO: 1226-1231; 8) SEQ ID NO: 1240-1245; 9) SEQ ID NO: 1254-1259; 10) SEQ IE ) NO: : 1268-1273; eleven) SEQ IE ) NO: : 1338-1343; 12) SEQ IE ) NO: : 1352-1357; 13) SEQ IE ) NO: : 1366-1371; 14) SEQ IE ) NO: : 1422-1427; And 15) SEQ IE ) NO: : 1436-1441.

These constructs are characterized, for example, by particularly high affinity, high cytotoxic activity (low EC50 values) and favorable interspecies affinity gap, as well as high sequence identity of VH and VL sequences to the human germline, low monomer to dimer conversion, high thermal stability, high plasma stability, low turbidity, high protein homogeneity, and an advantageous gap in specific monomer/dimer activity. In this context, it should be noted that these CDR amino acid sequences have a significantly higher sequence similarity, which is described in the following tables. 1 and 2.

Table 1

VH-CDR sequences of CD70 binding domain selection

VH-CDR1 VH-CDR2 VH-CDR3 SEQID NO CD70-13D_CC SYAMS VISGSGGRPNYAESVKG VDYSNYLFFDY 1044-1046 CD70-16D_CC SYAMS AISGSGGRT FYAE SVE G HDYSNYPYFDY 1086-1088 CD70-21D_CC TYAMS AISGSGGRT FYAE SVE G HDYSNYPYFDY 1142-1144 CD70-24D_CC SYAMS AISGSGGSTFYAESVKG HDYSNYPYFDY 1170-1172 CD70-25D_CC SYAMS AISGSGGRT FYAE SVE G HDYSNYPYFDY 1184-1186 CD70_l- G2D_CC SYAMS AISGSGGSTFYAESVQG HDYSNYPYFDY 1212-1214 CD70-27D_CC TYAMS AISGSGGGTFYAESVKG HDYSNYPYFDY 1226-1228 CD70-28D_CC TYAMS LISGSGGRTYYAESVKG HDYSNYPYFDY 1240-1242 CD70-31D_CC SYAMS AIS GS GGRAQYAE SVQG HDYSNYPYFDY 1254-1256 CD70-32D_CC SYAMS AISGSGGRT FYAE SVE G HDYSNYPYFDY 1268-1270 CD70-42D_CC TYAMS LISGSGGRTYYAESVKG HDYSNYPYFDY 1338-1340 CD70-43D_CC SYAMS AISGSGGRT FYAE SVE G HDYSNYPYFDY 1352-1354 CD70-48D_CC SYAMS VISGSGGITDFAESVKG HDYSNYFFFDY 1366-1368 CD70-62D_CC SYSMN YISSSGGYIYYAE SVKG GDYSNYAYFDY 1422-1424 CD70-13D_CC VYAMS TISGSGGSTFYAESVKG HDYSNYAYFDY 1436-1438

- 12 041992

table 2

VL-CDR sequences for selection of CD70 binding domains

VL-CDR1 VL-CDR2 VL-CDR3 SEQID NO CD70-13D_CC RAGQSVRSSYLG GASSRAT QQYGYSPPT 1047-1049 CD70-16D_CC RASQSIRSSYLA GASS RAT QQYGDLPFT 1089-1091 CD70-21D_CC RASQSVRSTYLA GASS RAT QQYGDLPFT 1145-1147 CD70-24D_CC RASQSVRSSYLA GASSRAT QQYGDLPFT 1173-1175 CD70-25D_CC RASQSVRSNYLA GASSRAT QQYGDLPFT 1187-1189 CD70_l-G2D_CC RASQSVRGNYLA GASSRAT QQYGYSPFT 1215-1217 CD70-27D_CC RASQSIRSNYLA GASSRAT QQYGSSPFT 1229-1231 CD70-28D_CC RASQSVRSNYLA GASNRAT QQYGISPPT 1243-1245 CD70-31D_CC RASQSVSSN-LA GSSSRAT QQYGSSPPP 1257-1259 CD70-32D_CC RASQGVRSDYLA GASSRAT QQYGSTPPT 1271-1273 CD70-42D_CC RASQGVRSSYLA GASS RAT QQYGSSPPT 1341-1343 CD70-43D_CC RASQSVRSNYLA GASS RAT QQYGSSPPT 1355-1357 CD70-48D_CC RASQGI-SNYLA AASILQS QQYFAYPIT 1369-1371 CD70-62D_CC RASQGI-SNYLA AASTLQS QQYYSTPLT 1425-1427 CD70-13D_CC RASQSVRSSYLA GASSRAT QQYGDLPFT 1439-1441

This marked sequence similarity, in the context of the overall biological/biochemical characteristics of the antibody constructs, allows for a consensus sequence for the six VH and VL CDRs. These consensus sequences are identified in the following. Therefore, it is an object of this invention to provide a bispecific antibody construct comprising a first binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell (and in one embodiment, at least macaque CD3), wherein the first binding domain contains a VH region containing CDR-H1, CDR-H2 and CDR-H3 and a VL region containing CDR-L1, CDR-L2 and CDR-L3, where said CDR-H1 has the amino acid the sequence X1YX2MX3 (SEQ ID NO: 1869), where X ₁ is S, T or V, X ₂ is A or S, and X ₃ is S or N;

said CDR-H2 has the amino acid sequence X1ISX2SGGX3X4X5X6AESVX7G (SEQ ID NO: 1870), where X1 is A, Y, V, L or T, X ₂ is G or S, X ₃ is R, Y, S, G or I, X ₄ is T, I, P or A, X5 is F, Y, N, Q or D, X ₆ is Y or F and X ₇ is E, K or Q;

said CDR-H3 has the amino acid sequence X1DYSNYX2X3FDY (SEQ ID NO: 1871), where X1 is H, G or V, X ₂ is P, A, L or F, and X ₃ is Y or F;

said CDR-L1 has the amino acid sequence RAX1QX ₂ X ₃ X ₄ X ₅ X ₆ X ₇ LX ₈ (SEQ ID NO: 1872), where X1 is S or G, X ₂ is S or G, X ₃ is I or V, X4 is R, S or no amino acid, X5 is S or G, X6 is S, N, T or D, X ₇ is Y or no amino acid, and X ₈ is A or G;

said CDR-L2 has the amino acid sequence X1X ₂ SX ₃ X ₄ X ₅ X ₆ (SEQ ID NO: 1873), where X ₁ is G or A, X ₂ is A or S, X ₃ is S, T, N or I, X4 is R or L, X5 is A or Q, and X6 is T or S; and said CDR-L3 has the amino acid sequence QQYX1X2X3PX4X5 (SEQ ID NO: 1874), where X1 is G, Y or F, X ₂ is D, S, Y, I or A, X ₃ is L, T, S or Y, X ₄ is F, L, P or I and X ₅ is T or P.

In addition, it is assumed that the specified CDR-H1 has the amino acid sequence SYSMN (SEQ ID NO: 1422) or X1YAMS (SEQ ID NO: 1875), where X1 represents S, T or V;

said CDR-H2 has an amino acid sequence selected from the group consisting of YISSSGGYIYYAESVKG (SEQ ID NO: 1423), VISGSGGITDFAESVKG (SEQ ID NO: 1367) and X1ISGSGGX2X3X4YAESVX5G (SEQ ID NO: 1876), where X1 is A, V, L or T, X ₂ is R, S, or G, X3 is T, P or A, X4 is F, N, Y or Q, and X5 is E, K or Q;

said CDR-H3 has an amino acid sequence selected from the group consisting of GDYSNYAYFDY (SEQ ID NO: 1424), HDYSNYFFFDY (SEQ ID NO: 1368), and X1DYSNYX2X3FDY

- 13 041992 (SEQ ID NO: 1877), where X ₁ represents H or V, X ₂ represents P, L or A, and X ₃ represents Y or F;

said CDR-L1 has the amino acid sequence RASQGISNYLA (SEQ ID NO: 1425) or RAX1QX ₂ X ₃ X ₄ X ₅ X ₆ YLX ₇ (SEQ ID NO: 1878), where X ₁ is S or G, X ₂ is S or G, X ₃ is I or V, X ₄ is R or S, X ₅ is S or G, X ₆ is S, T, N or D, and X ₇ is A or G;

said CDR-L2 has the amino acid sequence AASXLQS (SEQ ID NO: 1879) where X is T or I, or GX1SX2RAT (SEQ ID NO: 1880) where X1 is A or S and X2 is S or N; and said CDR-L3 has an amino acid sequence selected from the group consisting of QQYYSTPLT (SEQ ID NO: 1427), QQYFAYPIT (SEQ ID NO: 1371) and QQYGX1X2PX3X4 (SEQ ID NO: 1881), where X1 is D, Y, S or I, X ₂ is L, S or T, X ₃ is F or P, and X4 is T or P.

In addition, it is assumed that the specified CDR-H1 has the amino acid sequence X1YAMS (SEQ ID NO: 1875), where X1 represents S, T or V;

said CDR-H2 has the amino acid sequence X1ISGSGGX ₂ X ₃ X ₄ YAESVX ₅ G (SEQ ID NO: 1876), where X1 is A, V, L or T, X ₂ is R, S or G, X ₃ is T, P or A, X ₄ is F, N, Y or Q and X ₅ is E, K or Q;

said CDR-H3 has the amino acid sequence X1DYSNYX2X3FDY (SEQ ID NO: 1877), where X1 is H or V, X2 is P, L or A, and X3 is Y or F;

said CDR-L1 has the amino acid sequence RAX ₁ QX ₂ X ₃ X ₄ X ₅ X ₆ YLX ₇ (SEQ ID NO: 1878) where Xi is S or G, X ₂ is S or G, X ₃ is I or V, X4 is R or S, X ₅ is S or G, X ₆ is S, T, N or D, and X ₇ is A or G;

said CDR-L2 has the amino acid sequence GX1SX2RAT (SEQ ID NO: 1880), where X ₁ is A or S and X ₂ is S or N; and said CDR-L3 has the amino acid sequence QQYGX1X ₂ PX ₃ X ₄ (SEQ ID NO: 1881), where X ₁ is D, Y, S or I, X ₂ is L, S or T, X ₃ is F or P, and X ₄ is T or P.

Furthermore, said CDR-H1 is expected to have an amino acid sequence selected from the group consisting of SYAMS (SEQ ID NO: 1044), TYAMS (SEQ ID NO: 1142), VYAMS (SEQ ID NO: 1436), and SYSMN (SEQ ID NO: 1422);

said CDR-H2 has an amino acid sequence selected from the group consisting of AISGSGGRTFYAESVEG (SEQ ID NO: 1087), VISGSGGRPNYAESVKG (SEQ ID NO: 1045), AISGSGGSTFYAESVKG (SEQ ID NO: 1171), AISGSGGSTFYAESVQG (SEQ ID NO: 1213), AISGSGGGTFYAESVKG (SEQ ID NO: 1227), LISGSGGRTYYAESVKG (SEQ ID NO: 1241), AISGSGGRAQYAESVQG (SEQ ID NO: 1255), TISGSGGSTFYAESVKG (SEQ ID NO: 1437), YISSSGGYIYYAESVKG (SEQ ID NO: 1423) and VISGGITDQ IDFASEKG : 1367);

said CDR-H3 has an amino acid sequence selected from the group consisting of HDYSNYPYFDY (SEQ ID NO: 1088), VDYSNYLFFDY (SEQ ID NO: 1046), HDYSNYAYFDY (SEQ ID NO: 1438), GDYSNYAYFDY (SEQ ID NO: 1424), and HDYSNYFFFDY (SEQ ID NO: 1368);

said CDR-L1 has an amino acid sequence selected from the group consisting of RASQSIRSSYLA (SEQ ID NO: 1089), RASQSVRSTYLA (SEQ ID NO: 1145), RAGQSVRSSYLG (SEQ ID NO: 1047), RASQSVRSSYLA (SEQ ID NO: 1173), RASQSVRSNYLA (SEQ ID NO: 1187), RASQSVRGNYLA (SEQ ID NO: 1215), RASQSIRSNYLA (SEQ ID NO: 1229), RASQSVSSNLA (SEQ ID NO: 1257), RASQGVRSDYLA (SEQ ID NO: 1271), RASQGVRSSYLA (SEQ ID NO : 1341) and RASQGISNYLA (SEQ ID NO: 1369);

said CDR-L2 has an amino acid sequence selected from the group consisting of GASSRAT (SEQ ID NO: 1048), GASNRAT (SEQ ID NO: 1244), GSSSRAT (SEQ ID NO: 1258), AASTLQS (SEQ ID NO: 1426), and AASILQS (SEQ ID NO: 1370); and said CDR-L3 has an amino acid sequence selected from the group consisting of QQYGDLPFT (SEQ ID NO: 1091); QQYGYSPPT (SEQ ID NO: 1049), QQYGYSPFT (SEQ ID NO: 1217), QQYGSSPFT (SEQ ID NO: 1231), QQYGISPPT (SEQ ID NO: 1245), QQYGSSPPP (SEQ ID NO: 1259), QQYGSTPPT (SEQ ID NO : 1273), QQYGSSPPT (SEQ ID NO: 1343), QQYYSTPLT (SEQ ID NO: 1427), and QQYFAYPIT (SEQ ID NO: 1371).

The term variable refers to parts of antibodies or immunoglobulin domains that exhibit variability in their sequence and that are involved in determining the specificity and binding affinity of a particular antibody (ie variable domain(s)). Pairing of variable heavy chain (VH) and variable light chain (VL) together form one antigen-binding

- 14 041992 website.

Variability is distributed unevenly across all variable domains of antibodies; it is concentrated in subdomains of each of the heavy and light chain variable regions. These subdomains are called hypervariable regions or complementarity determining regions (CDRs). The more conserved (ie, non-hypervariable) portions of the variable domains are called framework regions (FRMs or FRs) and provide the basis for six CDRs in three-dimensional space to form an antigen-binding surface. Each of the native heavy and light chain variable domains contains four FRM regions (FR1, FR2, FR3, and FR4) predominantly adopting a β-sheet configuration, connected by three hypervariable regions that form loops connecting the β-sheet structure, and in some cases - forming part of the β-sheet structure. The hypervariable regions of each chain are joined to each other in close proximity by FRM and, together with the hypervariable regions of the other chain, participate in the formation of an antigen-binding site (see Kabat et al., loc. cit.).

The terms CDR and its multiple CDRs refer to the domain of complementarity, of which three make up the binding character of the light chain variable region (CDR-L1, CDR-L2 and CDR-L3) and three make up the binding character of the heavy chain variable region (CDR-H1, CDR -H2 and CDR-H3). CDRs contain most of the residues responsible for specific antibody-antigen interactions and therefore contribute to the functional activity of the antibody molecule: they are the main determinants of antigen specificity.

The specific boundaries and lengths of CDRs are defined by different classification and numbering systems. Therefore, CDRs may refer to Kabat, Chothia, contact, or any other boundary definition, including the numbering system described in this document. Despite different boundaries, each of these systems has some degree of overlap in what constitutes the so-called hypervariable regions in variable sequences. Thus, CDR definitions according to these systems may differ in length and boundary regions relative to the adjacent frame region. See, for example, Kabat (cross-species sequence variability approach), Chothia (antigen-antibody complex crystallographic approach), and/or MacCallum (Kabat et al., loc. cit.; Chothia et al., J Mol. Biol, 1987, 196:901-917 and MacCallum et al., J. Mol. Biol, 1996, 262:732). Another standard for characterizing an antigen binding site is the AbM definition used by Oxford Molecular's AbM antibody modeling software. See, for example, Protein Sequence and Structure Analysis of Antibody Variable Domains. B: Antibody Engineering Lab Manual (Ed.: Duebel, S. and Kontermann, R., Springer-Verlag, Heidelberg). To the extent that the two residue identification methods define regions of overlapping but not identical regions, they can be combined to define a hybrid CDR. However, numbering according to the so-called Rabat system is preferred.

As a rule, CDRs form a loop structure, which can be classified as a canonical structure. The term canonical structure refers to the backbone conformation that is accepted by antigen binding loops (CDRs). From comparative structural studies, five of the six antigen-binding loops were found to have only a limited repertoire of available conformations. Each canonical structure can be characterized by the twist angles of the polypeptide backbone. Thus, correlation loops between antibodies can have very similar three-dimensional structures despite high amino acid sequence variability in most parts of the loops (Chothia and Lesk, J. Mol. Biol, 1987, 196: 901; Chothia et al., Nature, 1989, 342: 877; Martin and Thornton, J. Mol. Biol, 1996, 263: 800). In addition, there is a relationship between the adopted loop structure and its amino acid sequences. The conformation of a particular canonical class is determined by the length of the loop and the amino acid residues found at key positions within the loop as well as within the conserved structure (i.e., outside the loop). Thus, the assignment of a particular canonical class can be based on the presence of these key amino acid residues.

The term canonical structure may also include considerations regarding the linear sequence of an antibody, such as as cataloged in Kabat (Kabat et al., Loc. Cit.). The Rabat numbering scheme is a widely accepted standard for numbering the amino acid residues of an antibody variable domain in a consistent manner and is the preferred scheme used in this invention, as also mentioned elsewhere herein. Additional structural considerations may also be used to determine the canonical structure of an antibody. For example, these differences, not fully reflected by Kabat's numbering, can be described by the numbering system of Chothia et al. and/or identified by other methods, such as crystallography and two- or three-dimensional computational modeling.

Accordingly, a given antibody sequence can be placed in a canonical class that allows, among other things, the identification of the corresponding chassis sequences (eg, based on the desire to include multiple canonical structures in the library). Rabat

- 15 041992 antibody amino acid sequence numbering and structural considerations as described by Chothia et al., loc. cit. and their implications for the interpretation of canonical aspects of antibody structure are described in the literature. The subunit structure and three-dimensional configuration of various classes of immunoglobulins are well known in the art. For a review of the structure of antibodies, see Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, eds. Harlow et al., 1988.

The light chain CDR3, and in particular the heavy chain CDR3, can form the most important antigen-binding determinants within the light and heavy chain variable regions. In some antibody constructs, the heavy chain CDR3 constitutes the major area of contact between antigen and antibody. In vitro selection schemes that vary only CDR3 can be used to vary the binding properties of an antibody or to determine which residues contribute to antigen binding. Therefore, CDR3 is typically the largest source of molecular diversity at an antibody binding site. H3, for example, may be shorter than two amino acid residues or have more than 26 amino acids.

In a classic full-length antibody or immunoglobulin, each L chain is linked to an H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds, depending on the isotype of the H chain. The CH domain closest to the VH is usually referred to as CH1. The constant (C) domains are not directly involved in antigen binding, but exhibit various effector functions such as antibody-dependent, cell-mediated cytotoxicity and complement activation. The Fc region of an antibody is contained within the heavy chain constant domains and, for example, can interact with Fc receptors located on the surface of cells.

The sequence of antibody genes after assembly and somatic mutation is highly variable, and these diverse genes are estimated to encode 10 ^{to 10} different antibody molecules (Immunoglobulin Genes, ^2nd ed., eds. Jonio et al., Academic Press, San Diego, CA, 1995 ). Accordingly, the immune system provides a repertoire of immunoglobulins. The term repertoire refers to at least one nucleotide sequence derived in whole or in part from at least one sequence encoding at least one immunoglobulin. The sequence(s) can be generated by in vivo rearrangement of the V, D and J segments of the heavy chains and the V and J segments of the light chains. Alternatively, the sequence(s) can be obtained from a cell in response to which a rearrangement occurs, for example, stimulation in vitro. Alternatively, part or all of the sequence(s) may be obtained by DNA splicing, nucleotide synthesis, mutagenesis and other methods, see, for example, US patent No. 5565332. The repertoire may include only one sequence or may include multiple sequences, including genetically diverse collection.

A preferred antibody construct of the invention can also be defined as a bispecific antibody construct comprising a first (preferably human) binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell, wherein the first binding domain binds to the same epitope on human CD70 as an antibody selected from the group consisting of CD70-1-CD70-74 and those specified in paragraphs 75-112 below, i.e. antibodies containing CDR-H1, CDR-H2 and CDR-H3 and a VL region containing CDR-L1, CDR-L2 and CDR-L3, where CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are selected from group consisting of groups represented in:

- 16 041992

1) SEQID NO: 1-6; 37) SEQ ID NO: 361-366 2) SEQID NO: 11-16; 38) SEQ ID NO: 371-376 3) SEQID NO: 21-26; 39) SEQ ID NO: 381-386 4) SEQID NO: 31-36; 40) SEQ ID NO: 391-396 5) SEQID NO: 41-46; 41) SEQ ID NO: 401-406 6) SEQID NO: 51-56; 42) SEQ ID NO: 411-416 7) SEQID NO: 61-66; 43) SEQ ID NO: 421-426 8) SEQID NO: 71-76; 44) SEQ ID NO: 431-436 9) SEQID NO: 81-86; 45) SEQ ID NO: 441-446 10) SEQID NO: 91-96; 46) SEQ ID NO: 451-456 eleven) SEQID NO: 101-106; 47) SEQ ID NO: 461-466 12) SEQID NO: 111-116; 48) SEQ ID NO: 471-476 13) SEQID NO: 121-126; 49) SEQ ID NO: 481-486 14) SEQID NO: 131-136; 50) SEQ ID NO: 491-496 15) SEQID NO: 141-146; 51) SEQ ID NO: 501-506 16) SEQID NO: 151-156; 52) SEQ ID NO: 511-516 17) SEQID NO: 161-166; 53) SEQ ID NO: 521-526 18) SEQID NO: 171-176; 54) SEQ ID NO: 531-536 19) SEQID NO: 181-186; 55) SEQ ID NO: 541-546 20) SEQID NO: 191-196; 56) SEQ ID NO: 551-556 21) SEQID NO: 201-206; 57) SEQ ID NO: 561-566 22) SEQID NO: 211-216; 58) SEQ ID NO: 571-576 23) SEQID NO: 221-226; 59) SEQ ID NO: 581-586 24) SEQID NO: 231-236; 60) SEQ ID NO: 591-596 25) SEQID NO: 241-246; 61) SEQ ID NO: 601-606 26) SEQID NO: 251-256; 62) SEQ ID NO: 611-616 27) SEQID NO: 261-266; 63) SEQ ID NO: 621-626 28) SEQID NO: 271-276; 64) SEQ ID NO: 631-636 29) SEQID NO: 281-286; 65) SEQ ID NO: 641-646 thirty) SEQID NO: 291-296; 66) SEQ ID NO: 651-656 31) SEQID NO: 301-306; 67) SEQ ID NO: 661-666 32) SEQID NO: 311-316; 68) SEQ ID NO: 671-676 33) SEQID NO: 321-326; 69) SEQ ID NO: 681-686 34) SEQID NO: 331-336; 70) SEQ ID NO: 691-696 35) SEQID NO: 341-346; 71) SEQ ID NO: 701-706 36) SEQID NO: 351-356; 72) SEQ ID NO: 711-716

- 17 041992

73) SEQ ID NO: 721-726; 109) SEQ ID NO: 1520-1525; 74) SEQ ID NO: 731-736; 110) SEQ ID NO: 1534-1539; 75) SEQ ID NO: 1044-1049; 111) SEQ ID NO: 1548-1553; And 76) SEQ ID NO: 1058-1063; 112) SEQ ID NO: 1562-1567. 77) SEQ ID NO: 1072-1077; 78) SEQ ID NO: 1086-1091; 79) SEQ ID NO: 1100-1005; 80) SEQ ID NO: 1114-1119; 81) SEQ ID NO: 1128-1133; 82) SEQ ID NO: 1142-1147; 83) SEQ ID NO: 1156-1161; 84) SEQ ID NO: 1170-1175; 85) SEQ ID NO: 1184-1189; 86) SEQ ID NO: 1198-1203; 87) SEQ ID NO: 1212-1217; 88) SEQ ID NO: 1226-1231; 89) SEQ ID NO: 1240-1245; 90) SEQ ID NO: 1254-1259; 91) SEQ ID NO: 1268-1273; 92) SEQ ID NO: 1282-1287; 93) SEQ ID NO: 1296-1301; 94) SEQ ID NO: 1310-1315; 95) SEQ ID NO: 1324-1329; 96) SEQ ID NO: 1338-1343; 97) SEQ ID NO: 1352-1357; 98) SEQ ID NO: 1366-1371; 99) SEQ ID NO: 1380-1385;

100) SEQ ID NO: 1394-1399 101) SEQ ID NO: 1408-1413 102) SEQ ID NO: 1422-1427 103) SEQ ID NO: 1436-1441 104) SEQ ID NO: 1450-1455 105) SEQ ID NO: 1464-1469 106) SEQ ID NO: 1478-1483 107) SEQ ID NO: 1492-1497 108) SEQ ID NO: 1506-1511

Whether an antibody construct binds to the same CD70 epitope as another antibody construct can be determined, for example, by epitope mapping with chimeric or truncated target molecules, for example, as described above and in Example 2.

A preferred antibody construct of the invention can also be defined as a bispecific antibody construct comprising a first (preferably human) binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell, wherein the first binding domain competes for binding with an antibody selected from the group consisting of CD70-1 to CD7074 and those specified in paragraphs 75 to 112 above, i.e. an antibody containing a VH region containing CDR-H1, CDR-H2 and a CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of the groups described in 1-112 above.

Whether an antibody construct competes for binding with another given antibody construct, in a competitive assay, such as a competitive ELISA (enzyme-linked immunosorbent assay) or a cellular competition assay. Avidin-bound microparticles (beads) can also be used. Like an avidin-coated ELISA plate, when interacting with a biotinylated protein, each of these beads can be used as a substrate on which the assay can be performed. The antigen is applied to the bead and then pre-coated with the first antibody. A second antibody is added and any additional binding determined. Reading is done by flow cytometry. See fig. 2.

- 18 041992

In one embodiment, the first binding domain of an antibody construct of the invention comprises a VH region selected from the group consisting of the regions shown in SEQ ID NO: 7, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID

NO: 67, SEQ ID NO: 77, SEQ ID NO: 87, SEQ ID NO: 97, SEQ ID NO

127 SEQ ID NO

187 SEQ ID NO

247 SEQ ID NO

307 SEQ ID NO

367 SEQ ID NO

427 SEQ ID NO

487 SEQ ID NO

547 SEQ ID NO

607 SEQ ID NO

667 SEQ ID NO

727 SEQ ID NO

936 SEQ ID NO

960 SEQ ID NO

137 SEQ ID NO

197 SEQ ID NO

257 SEQ ID NO

317 SEQ ID NO

377 SEQ ID NO

437 SEQ ID NO

497 SEQ ID NO

557 SEQ ID NO

617 SEQ ID NO

677 SEQ ID NO

737 SEQ ID NO

940 SEQ ID NO

964 SEQ ID NO

147 SEQ ID NO

207 SEQ ID NO

267 SEQ ID NO

327 SEQ ID NO

387 SEQ ID NO

447 SEQ ID NO

507 SEQ ID NO

567 SEQ ID NO

627 SEQ ID NO

687 SEQ ID NO

920 SEQ ID NO

944 SEQ ID NO

968 SEQ ID NO

157 SEQ ID NO

217 SEQ ID NO

277 SEQ ID NO

337 SEQ ID NO

397 SEQ ID NO

457 SEQ ID NO

517 SEQ ID NO

577 SEQ ID NO

637 SEQ ID NO

697 SEQ ID NO

924 SEQ ID NO

948 SEQ ID NO

972 SEQ ID NO

107 SEQ ID NO

167 SEQ ID NO

227 SEQ ID NO

287 SEQ ID NO

347 SEQ ID NO

407 SEQ ID NO

467 SEQ ID NO

527 SEQ ID NO

587 SEQ ID NO

647 SEQ ID NO

707 SEQ ID NO

928 SEQ ID NO

952 SEQ ID NO

976 SEQ ID NO

117, SEQ ID NO 177, SEQ ID NO 237, SEQ ID NO 297, SEQ ID NO 357, SEQ ID NO 417, SEQ ID NO 477, SEQ ID NO 537, SEQ ID NO 597, SEQ ID NO 657, SEQ ID NO 717, SEQ ID NO 932, SEQ ID NO 956, SEQ ID NO 980, SEQ ID NO

984, SEQ ID NO: 988, SEQ ID NO: 992, SEQ ID NO: 996, SEQ ID NO: 1000, SEQ ID NO: 1004, SEQ ID NO

1008, SEQ ID NO: 1012, SEQ ID NO: 1016, SEQ ID NO: 1020, SEQ ID NO: 1024, SEQ ID NO: 1028, SEQ ID NO: 1032, SEQ ID NO: 1036, SEQ ID NO: 1040, SEQ ID NO: 1050, SEQ ID NO: 1054, SEQ ID NO: 1064, SEQ ID NO: 1068, SEQ ID NO: 1078, SEQ ID NO: 1082, SEQ ID NO: 1092, SEQ ID NO: 1096, SEQ ID NO: 1106, SEQ ID NO: 1110, SEQ ID NO: 1120, SEQ ID NO: 1124, SEQ ID NO: 1134, SEQ ID NO: 1138, SEQ ID NO: 1148, SEQ ID NO: 1152, SEQ ID NO: 1162, SEQ ID NO: 1166, SEQ ID NO: 1176, SEQ ID NO: 1180, SEQ ID NO: 1190, SEQ ID NO: 1194, SEQ ID NO: 1204, SEQ ID NO: 1208, SEQ ID NO: 1218, SEQ ID NO: 1222, SEQ ID NO: 1232, SEQ ID NO: 1236, SEQ ID NO: 1246, SEQ ID NO: 1250, SEQ ID NO: 1260, SEQ ID NO: 1264, SEQ ID NO: 1274, SEQ ID NO: 1278, SEQ ID NO: 1288, SEQ ID NO: 1292, SEQ ID NO: 1302, SEQ ID NO: 1306, SEQ ID NO: 1316, SEQ ID NO: 1320, SEQ ID NO: 1330, SEQ ID NO: 1334, SEQ ID NO: 1344, SEQ ID NO: 1348, SEQ ID NO: 1358, SEQ ID NO: 1362, SEQ ID NO: 1372, SEQ ID NO: 1376, SEQ ID NO: 1386, SEQ ID NO: 1390, SEQ ID N O: 1400, SEQ ID NO: 1404, SEQ ID NO: 1414, SEQ ID NO: 1418, SEQ ID NO: 1428, SEQ ID NO: 1432, SEQ ID NO: 1442, SEQ ID NO: 1446, SEQ ID NO: 1456, SEQ ID NO: 1460, SEQ ID NO: 1470, SEQ ID NO: 1474, SEQ ID NO: 1484, SEQ ID NO: 1488, SEQ ID NO: 1498, SEQ ID NO: 1502, SEQ ID NO: 1512, SEQ ID NO: 1516, SEQ ID NO: 1526, SEQ ID NO: 1530, SEQ ID NO: 1540, SEQ ID NO: 1544, SEQ ID NO: 1554, SEQ ID NO: 1558, SEQ ID NO: 1568 and SEQ ID NO: 1572.

It is preferred if the first binding domain of the antibody construct of the invention comprises a VH region selected from the group consisting of the regions shown in SEQ ID NO: 1050, SEQ ID NO: 1092, SEQ ID NO: 1148, SEQ ID NO: 1176, SEQ ID NO: 1190, SEQ ID NO: 1218, SEQ ID NO: 1232, SEQ ID NO: 1246, SEQ ID NO: 1260, SEQ ID NO: 1274, SEQ ID NO: 1344, SEQ ID NO: 1358, SEQ ID NO : 1372, SEQ ID NO: 1428 and SEQ ID NO: 1442.

In another embodiment, the first binding domain of an antibody construct of the invention comprises a VL region selected from the group consisting of the regions shown in SEQ ID NO: 8, SEQ ID NO: 18, SEQ ID NO: 28, SEQ ID NO: 38, SEQ ID NO: 48, SEQ ID NO: 58, SEQ ID

NO: 68, SEQ ID NO: 78, SEQ ID NO: 88, SEQ ID NO: 98, SEQ ID NO

128 SEQ ID NO

188 SEQ ID NO

248 SEQ ID NO

308 SEQ ID NO

368 SEQ ID NO

428 SEQ ID NO

488 SEQ ID NO

548 SEQ ID NO

608 SEQ ID NO

668 SEQ ID NO

728 SEQ ID NO

937 SEQ ID NO

961 SEQ ID NO

138 SEQ ID NO

198 SEQ ID NO

258 SEQ ID NO

318 SEQ ID NO

378 SEQ ID NO

438 SEQ ID NO

498 SEQ ID NO

558 SEQ ID NO

618 SEQ ID NO

678 SEQ ID NO

738 SEQ ID NO

941 SEQ ID NO

965 SEQ ID NO

148 SEQ ID NO

208 SEQ ID NO

268 SEQ ID NO

328 SEQ ID NO

388 SEQ ID NO

448 SEQ ID NO

508 SEQID NO

568 SEQ ID NO

628 SEQ ID NO

688 SEQ ID NO

921 SEQ ID NO

945 SEQ ID NO

969 SEQ ID NO

158 SEQ ID NO

218 SEQ ID NO

278 SEQ ID NO

338 SEQ ID NO

398 SEQ ID NO

458 SEQ ID NO

518 SEQ ID NO

578 SEQ ID NO

638 SEQ ID NO

698 SEQ ID NO

925 SEQ ID NO

949 SEQ ID NO

973 SEQ ID NO

108 SEQ ID NO

168 SEQ ID NO

228 SEQ ID NO

288 SEQ ID NO

348 SEQ ID NO

408 SEQ ID NO

468 SEQ ID NO

528 SEQ ID NO

588 SEQ ID NO

648 SEQ ID NO

708 SEQ ID NO

929 SEQ ID NO

953 SEQ ID NO

977 SEQ ID NO

118, SEQ ID NO 178, SEQ ID NO 238, SEQ ID NO 298, SEQ ID NO 358, SEQ ID NO 418, SEQ ID NO 478, SEQ ID NO 538, SEQ ID NO 598, SEQ ID NO 658, SEQ ID NO 718, SEQ ID NO 933, SEQ ID NO 957, SEQ ID NO 981, SEQ ID NO

985, SEQ ID NO: 989, SEQ ID NO: 993, SEQ ID NO: 997, SEQ ID NO: 1001, SEQ ID NO: 1005, SEQ ID NO

1009, SEQ ID NO: 1013, SEQ ID NO: 1017, SEQ ID NO: 1021, SEQ ID NO: 1025, SEQ ID NO: 1029, SEQ ID NO: 1033, SEQ ID NO: 1037, SEQ ID NO: 1041, SEQ ID NO: 1051, SEQ ID NO: 1055, SEQ ID NO: 1065, SEQ ID NO: 1069, SEQ ID NO: 1079, SEQ ID NO: 1083, SEQ ID NO: 1093, SEQ ID NO: 1097, SEQ ID NO: 1107, SEQ ID NO: 1111, SEQ ID NO: 1121, SEQ ID NO: 1125, SEQ ID NO: 1135, SEQ ID NO: 1139, SEQ ID NO: 1149, SEQ ID NO: 1153, SEQ ID NO: 1163, SEQ ID NO: 1167, SEQ ID NO: 1177, SEQ ID NO: 1181, SEQ ID NO: 1191, SEQ ID NO: 1195, SEQ ID NO: 1205, SEQ ID NO: 1209, SEQ ID NO: 1219, SEQID NO:

- 19 041992

1223, SEQ ID NO: 1233, SEQ ID NO: 1237, SEQ ID NO: 1247, SEQ ID NO: 1251, SEQ ID NO: 1261, SEQ ID NO: 1265, SEQ ID NO: 1275, SEQ ID NO: 1279, SEQ ID NO: 1289, SEQ ID NO: 1293, SEQ ID NO: 1303, SEQ ID NO: 1307, SEQ ID NO: 1317, SEQ ID NO: 1321, SEQ ID NO: 1331, SEQ ID NO: 1335, SEQ ID NO: 1345, SEQ ID NO: 1349, SEQ ID NO: 1359, SEQ ID NO: 1363, SEQ ID NO: 1373, SEQ ID NO: 1377, SEQ ID NO: 1387, SEQ ID NO: 1391, SEQ ID NO: 1401, SEQ ID NO: 1405, SEQ ID NO: 1415, SEQ ID NO: 1419, SEQ ID NO: 1429, SEQ ID NO: 1433, SEQ ID NO: 1443, SEQ ID NO: 1447, SEQ ID NO: 1457, SEQ ID NO: 1461, SEQ ID NO: 1471, SEQ ID NO: 1475, SEQ ID NO: 1485, SEQ ID NO: 1489, SEQ ID NO: 1499, SEQ ID NO: 1503, SEQ ID NO: 1513, SEQ ID NO: 1517, SEQ ID NO: 1527, SEQ ID NO: 1531, SEQ ID NO: 1541, SEQ ID NO: 1545, SEQ ID NO: 1555, SEQ ID NO: 1559, SEQ ID NO: 1569 and SEQ ID NO: 1573.

It is preferred if the first binding domain of the antibody construct of the invention comprises a VL region selected from the group consisting of the regions shown in SEQ ID NO: 1051, SEQ ID NO: 1093, SEQ ID NO: 1149, SEQ ID NO: 1177, SEQ ID NO: 1191, SEQ ID NO: 1219, SEQ ID NO: 1233, SEQ ID NO: 1247, SEQ ID NO: 1261, SEQ ID NO: 1275, SEQ ID NO: 1345, SEQ ID NO: 1359, SEQ ID NO : 1373, SEQ ID NO: 1429 and SEQ ID NO: 1443.

In another embodiment, the first binding domain of an antibody construct of the invention comprises a VH region and a VL region selected from the group consisting of pairs of a VH region and a VL region as shown in SEQ ID NO: 7+8, SEQ ID NO: 17+18, SEQ ID NO: 27+28, SEQ ID NO: 37+38, SEQ ID NO: 47+48, SEQ ID NO: 57+58, SEQ ID NO: 67+68, SEQ ID NO: 77+78, SEQ ID NO: 87+88, SEQ ID NO: 97+98, SEQ ID NO: 107+108, SEQ ID NO: 117+118, SEQ ID NO: 127+128, SEQ ID NO: 137+138, SEQ ID NO: 147 + 148, SEQ ID NO: 157 + 158, SEQ ID NO: 167 + 168, SEQ ID NO: 177 + 178, SEQ ID NO: 187 + 188, SEQ ID NO: 197 + 198, SEQ ID NO: 207 + 208, SEQ ID NO: 217+218, SEQ ID NO: 227+228, SEQ ID NO: 237+238, SEQ ID NO: 247+248, SEQ ID NO: 257+258, SEQ ID NO: 267+268, SEQ ID NO: 277+278, SEQ ID NO: 287+288, SEQ ID NO: 297+298, SEQ ID NO: 307+308, SEQ ID NO: 317+318, SEQ ID NO: 327+328, SEQ ID NO: 337+338, SEQ ID NO: 347+348, SEQ ID NO: 357+358, SEQ ID NO: 367+368, SEQ ID NO: 377+378, S EQ ID NO: 387+388, SEQ ID NO: 397+398, SEQ ID NO: 407+408, SEQ ID NO: 417+418, SEQ ID NO: 427+428, SEQ ID NO: 437+438, SEQ ID NO: 447 + 448, SEQ ID NO: 457 + 458, SEQ ID NO: 467 + 468, SEQ ID NO: 477 + 478, SEQ ID NO: 487 + 488, SEQ ID NO: 497 + 498, SEQ ID NO: 507+508, SEQ ID NO: 517+518, SEQ ID NO: 527+528, SEQ ID NO: 537+538, SEQ ID NO: 547+548, SEQ ID NO: 557+558, SEQ ID NO: 567+ 568, SEQ ID NO: 577+578, SEQ ID NO: 587+588, SEQ ID NO: 597+598, SEQ ID NO: 607+608, SEQ ID NO: 617+618, SEQ ID NO: 627+628, SEQ ID NO: 637+638, SEQ ID NO: 647+648, SEQ ID NO: 657+658, SEQ ID NO: 667+668, SEQ ID NO: 677+678, SEQ ID NO: 687+688, SEQ ID NO: 697+698, SEQ ID NO: 707+708, SEQ ID NO: 717+718, SEQ ID NO: 727+728, SEQ ID NO: 737+738, SEQ ID NO: 920+921, SEQ ID NO: 924+925, SEQ ID NO: 928+929, SEQ ID NO: 932+933, SEQ ID NO: 936+937, SEQ ID NO: 940+941, SEQ ID NO: 944+945, SEQ ID NO: 948+ 949, SEQ ID NO: 952 + 953, SEQ ID NO: 95 6+957, SEQ ID NO: 960+961, SEQ ID NO: 964+965, SEQ ID NO: 968+969, SEQ ID NO: 972+973, SEQ ID NO: 976+977, SEQ ID NO: 980+ 981, SEQ ID NO: 984+985, SEQ ID NO: 988+989, SEQ ID NO: 992+993, SEQ ID NO: 996+997, SEQ ID NO: 1000+1001, SEQ ID NO: 1004+1005, SEQ ID NO: 1008+1009, SEQ ID NO: 1012+1013, SEQ ID NO: 1016+1017, SEQ ID NO: 1020+1021, SEQ ID NO: 1024+1025, SEQ ID NO: 1028+1029, SEQ ID NO: 1032+1033, SEQ ID NO: 1036+1037, SEQ ID NO: 1040+1041, SEQ ID NO: 1050+1051, SEQ ID NO: 1054+1055, SEQ ID NO: 1064+1065, SEQ ID NO: 1068+1069, SEQ ID NO: 1078+1079, SEQ ID NO: 1082+1083, SEQ ID NO: 1092+1093, SEQ ID NO: 1096+1097, SEQ ID NO: 1106+1107, SEQ ID NO: 1110+ 1111, SEQ ID NO: 1120+1121, SEQ ID NO: 1124+1125, SEQ ID NO: 1134+1135, SEQ ID NO: 1138+1139, SEQ ID NO: 1148+1149, SEQ ID NO: 1152+1153, SEQ ID NO: 1162+1163, SEQ ID NO: 1166+1167, SEQ ID NO: 1176+1177, SEQ ID NO: 1180+1181, SEQ ID NO: 1190+1191, SEQ ID NO: 1194+1195, SEQ IDNO: 1204+1205, SEQ ID NO: 1208+1209, SEQ ID NO: 1218+1219, SEQ ID NO: 1222+1223, SEQ ID NO: 1232+1233, SEQ ID NO: 1236+1237, SEQ ID NO: 1246+1247, SEQ ID NO: 1250+1251, SEQ ID NO: 1260+1261, SEQ ID NO: 1264+1265, SEQ ID NO: 1274+1275, SEQ ID NO: 1278+1279, SEQ ID NO: 1288+ 1289, SEQ ID NO: 1292+1293, SEQ ID NO: 1302+1303, SEQ ID NO: 1306+1307, SEQ ID NO: 1316+1317, SEQ ID NO: 1320+1321, SEQ ID NO: 1330+1331, SEQ ID NO: 1334+1335, SEQ ID NO: 1344+1345, SEQ ID NO: 1348+1349, SEQ ID NO: 1358+1359, SEQ ID NO: 1362+1363, SEQ ID NO: 1372+1373, SEQ ID NO: 1376+1377, SEQ ID NO: 1386+1387, SEQ ID NO: 1390+1391, SEQ ID NO: 1400+1401, SEQ ID NO: 1404+1405, SEQ ID NO: 1414+1415, SEQ ID NO: 1418+1419, SEQ ID NO: 1428+1429, SEQ ID NO: 1432+1433, SEQ ID NO: 1442+1443, SEQ ID NO: 1446+1447, SEQ ID NO: 1456+1457, SEQ ID NO: 1460+ 1461, SEQ ID NO: 1470+1471, SEQ ID NO: 1474+1475, SEQ ID NO: 1484+1485, SEQ ID NO: 1488+1489, SEQ ID NO: 1498+1499, SEQ ID NO : 1502+1503, SEQ ID NO: 1512+1513, SEQ ID NO: 1516+1517, SEQ ID NO: 1526+1527, SEQ ID NO: 1530+1531, SEQ ID NO: 1540+1541, SEQ ID NO: 1544 +1545, SEQ ID NO: 1554+1555, SEQ ID NO: 1558+1559, SEQ ID NO: 1568+1569 and SEQ ID NO: 1572+1573.

It is preferred that the first binding domain of an antibody construct of the invention comprises a VH region and a VL region selected from the group consisting of VH region and VL region pairs as shown in SEQ ID NO: 1050 + 1051, SEQ ID NO: 1092 + 1093, SEQ ID NO: 1148+1149, SEQ ID NO: 1176+1177, SEQ ID NO: 1190+1191, SEQ ID NO: 1218+1219, SEQ ID NO: 1232+1233, SEQ ID NO:

- 20 041992

1246+1247, SEQ ID NO: 1260+1261, SEQ ID NO: 1274+1275, SEQ ID NO: 1344+1345, SEQ ID NO:

1358+1359, SEQ ID NO: 1372+1373, SEQ ID NO: 1428+1429 and SEQ ID NO: 1442+1443.

In yet another embodiment, the first binding domain of an antibody construct of the invention comprises a polypeptide selected from the group consisting of the polypeptides shown in SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO:

59, SEQ ID NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO: 109, SEQ ID NO: 119,

SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO: SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

179, 239, 299, 359, 419, 479, 539, 599, 659, 719, 934, 958, 982,

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, 1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO:

1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID NO: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID N O: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574.

It is preferred that the first binding domain of the antibody construct of the invention comprises a polypeptide selected from the group consisting of those shown in SEQ ID NO: 1052, SEQ ID NO: 1094, SEQ ID NO: 1150, SEQ ID NO: 1178, SEQ ID NO: 1192, SEQ ID NO: 1220, SEQ ID NO: 1234, SEQ ID NO: 1248, SEQ ID NO: 1262, SEQ ID NO: 1276, SEQ ID NO: 1346, SEQ ID NO: 1360, SEQ ID NO: 1374, SEQ ID NO: 1430 and SEQ ID NO: 1444.

As used herein, the term bispecific refers to an antibody construct that is at least bispecific, i.e. it contains at least a first binding domain and a second binding domain, where the first binding domain binds to a single antigen or target (in this specification: CD70) , and the second binding domain binds to another antigen or target (in this document: CD3). Accordingly, the antibody constructs of the invention contain specificities for at least two different antigens or targets. The term bispecific antibody construct of the invention also encompasses multispecific antibody constructs, such as trispecific antibody constructs, the latter of which contain three binding domains or constructs having more than three (eg four, five...) specificities.

Given that the antibody constructs of the invention are (at least) bispecific, they do not naturally occur and they differ markedly from natural products. Thus, a bispecific antibody construct or immunoglobulin is an artificial fusion antibody or immunoglobulin having at least two different binding sites with different specificities. Bespecifically construct antibodies can be obtained in various ways, including through the fusion of hybridomas or linking Fab' fragments. See, for example, Songsivilai & Lachmann, Clin. Exp. Immunol. 79:315-321 (1990).

The at least two binding domains and variable domains of an antibody construct of the invention may or may not contain peptidic linkers (spacer peptides). The term peptide linker according to the invention comprises an amino acid sequence by which the amino acid sequences of one (variable and/or binding) domain and another (variable and/or binding) domain of an antibody construct of the invention are linked to each other. An essential technical feature of such a peptide linker is that it does not have any polymerization activity. Suitable peptide linkers include those described in US Pat. Nos. 4,751,180 and 4,935,233 or WO 88/09344. Peptide linkers can also be used to attach other domains or modules or regions (such as half-life increasing domains) to an antibody construct of the invention.

Where a linker is used, the linker is preferably of sufficient length and sequence to ensure that each of the first and second domains can independently maintain their differential binding specificities. For peptide linkers that connect at least two binding domains (or two variable domains) in an antibody construct of the invention, peptide linkers that contain only a small number of amino acid residues, such as 12 amino acid residues or less, are preferred. Thus, a peptide linker of 12, 11, 10, 9, 8, 7, 6 or 5 amino acid residues is preferred. A putative peptide linker with less than 5 amino acids contains 4, 3, 2, or one amino acid(s), with Gly-rich linkers being preferred. A particularly preferred single amino acid in the context of said peptide linker is Gly. Suitably, said peptide linker may consist of a single Gly amino acid. Another preferred embodiment of the peptide linker is characterized by the amino acid sequence Gly-Gly-Gly-Gly-Ser, i.e. Gly4Ser (SEQ ID NO: 771), or polymers thereof, i.e. (Gly ₄ Ser)x, where x is an integer equal to 1 or more (eg 2 or 3). Preferred linkers are shown in SEQ ID NO: 770-778. The characteristics of said peptide linker, which include the lack of promotion of secondary structures, are known in the art and are described, for example, in Dall'Acqua et al. (Biochem. (1998) 37, 9266-9273), Cheadle et al. (Mol Immunol (1992) 29, 21-30) and Raag and Whitlow (FASEB (1995) 9(1), 73-80). Preferred are peptide linkers which also do not promote the formation of any secondary structures. Linking these domains to each other can be achieved, for example, using genetic engineering, as described in the examples. Methods for preparing fused and operably linked bispecific single strand constructs and expressing them in bacterial or mammalian cells are well known in the art (e.g., WO 99/54440 or Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2001).

As described above herein, the invention provides a preferred embodiment wherein the antibody construct is in a format selected from the group consisting of (scFv) ₂ , single domain-scFv mAb, diabody, and oligomers of any of the above formats. The term is in the format does not exclude that the design can be further modified by attaching or merging with other fragments, as described in this document.

According to a particularly preferred embodiment of the invention, and as described in the accompanying examples, the antibody construct of the invention is a bispecific single chain antibody construct, more preferably a bispecific single chain Fv (scFv). Although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be combined using standard recombinant techniques through a synthetic linker - as described earlier in this document - which allows them to be obtained as a single protein chain, in in which the VL and VH regions are paired to form a monovalent molecule; see, for example, Huston et al. (1988) Proc. Natl. Acad. Sci USA 85:5879-5883). These antibody fragments are prepared using conventional methods known to those skilled in the art and the fragments are evaluated for function in the same manner as whole or full length antibodies. A single chain variable fragment (scFv) is therefore an immunoglobulin heavy chain (VH) and light chain (VL) variable region fusion protein, typically associated with a short linker peptide of about 10 to about 25 amino acids, preferably about 15 to 20 amino acids. The linker is usually rich in glycine for flexibility and serine or threonine for solubility, and can either connect the N-terminus of the VH to the C-terminus of the VL, or vice versa. This protein retains the specificity of the original immunoglobulin despite the removal of constant regions and the introduction of a linker.

Bispecific single chain molecules are known in the art and are described in WO 99/54440, Mack, J. Immunol. (1997), 158, 3965-3970, Mack, PNAS, (1995), 92, 7021-7025, Kufer, Cancer Immunol. Immunother., (1997), 45, 193-197, Loffler, Blood, (2000), 95, 6, 2098-2103, Burhl, Immunol., (2001), 166, 2420-2426, Kipriyanov, J. Mol. Biol., (1999), 293, 41-56. The methods described for the production of single chain antibodies (see, in particular, US patent No. 4946778, Kontermann and Dubel (2010), loc. cit. and Little (2009), loc. cit.) can be adapted to obtain single chain antibody constructs specifically recognizing the chosen target(s).

Bivalent (also referred to as divalent) or bispecific single chain variable fragments (bi-scFvs or di-scFvs having the (scFv)2 format can be constructed by linking two scFv molecules (eg, with linkers as described above herein). If these two scFv molecules have the same binding specificity, the resulting (scFv) ₂ molecule pre

- 22 041992 will respectfully be called bivalent (ie it has two valences for the same target epitope). If two scFv molecules have different binding specificities, the resulting (scFv)2 molecule will preferably be referred to as bispecific. Coupling can be accomplished by creating a single peptide chain with two VH and two VL regions to form tandem scFvs (see, for example, Kufer P. et al., (2004) Trends in Biotechnology 22(5):238-244). Another possibility is to design scFv molecules with linker peptides that are too short for the two variable regions to add up (eg, about five amino acids), causing the scFvs to dimerize. This type is known as a diabody (see, for example, Hollinger, Philipp et al., (July 1993) Proceedings of the National Academy of Sciences of the United States of America 90(14):6444-8.).

According to yet another preferred embodiment of the antibody design of the invention, the heavy chain (VH) and light chain (VL) of the binding domain (binding to either the target CD70 antigen or CD3) are not directly linked via a peptide linker as described above, but binding domains are formed as described for the diabody. Thus, a VH of a CD3 binding domain can be fused to a VL of a CD70 binding domain using a peptide linker, and a VH of a CD70 binding domain is fused to a VL of a CD3 binding domain via such a peptide linker.

Single domain antibodies contain only one (monomeric) antibody variable domain, which is capable of selectively binding to a particular antigen independently of other V regions or domains. The first single domain antibodies were constructed from heavy chain antibodies found in camelids and these are called V _H H fragments. Cartilaginous fish also have heavy chain antibodies (IgNAR) from which single domain antibodies called V _NAR fragments can be derived. An alternative approach is to separate the dimeric variable domains from common immunoglobulins, eg, from human or rodent, into monomers, hence obtaining VH or VL as a single domain Ab. While most research on single-domain antibodies to date is based on heavy chain variable domains, light chain-derived nanoparticles have been shown to specifically bind to targeted epitopes. Examples of single domain antibodies are called sdAbs, nanoparticles, or single variable domain antibodies.

Thus (single domain mAb) ₂ is a monoclonal antibody construct consisting of (at least) two single domain monoclonal antibodies individually selected from the group consisting of VH, VL, VHH and V _NAR . The linker is preferably in the form of a peptide linker. Similarly, a scFv single domain mAb is a monoclonal antibody consisting of at least one single domain antibody as described above and one scFv molecule as described above. Again, the linker is preferably in the form of a peptide linker.

It is also contemplated that the antibody construct of the invention has, in addition to its function of binding to CD70 and CD3 target molecules, another function. In this format, an antibody construct is a trifunctional or multifunctional antibody construct that functions by targeting target cells via CD70 binding, mediating T cell cytotoxic activity via CD3 binding, and conferring an additional function such as antibody-dependent cellular cytotoxicity mediated by a fully functional constant domain. Fc, by recruiting effector cells such as NK cells, labels (fluorescent, etc.), therapeutic agents such as a toxin or radionuclide, and/or agents for increasing serum half-life, etc.

Examples of means for extending the serum half-life of the antibody constructs of the invention include peptides, proteins, or protein domains that are fused or otherwise attached to the antibody constructs. The group of peptides, proteins or protein domains includes peptides that bind to other proteins with a preferred pharmacokinetic profile in the human body, such as serum albumin (see WO 2009/127691). An alternative embodiment of such half-life-prolonging peptides includes peptides that bind to the neonatal Fc receptor (FcRn, see WO 2007/098420), which are also used in some of the constructs of this invention. The option of attaching larger protein domains or complete proteins includes, for example, fusion of human serum albumin, human serum albumin variants or mutants (see WO 2011/051489, WO 2012/059486, WO 2012/150319, WO 2013/135896, WO 2014/ 072481, WO 2013/075066) or their domains, as well as the fusion of the constant region of immunoglobulins (Fc domains) and their variants. Such Fc domain variants can be optimized/modified to provide the desired pairing of dimers or multimers, to prevent Fc receptor (eg, Fcy receptor) binding, or for other reasons. Another option known in the art for extending the half-life of small protein compounds in the human body is the pegylation of these compounds, such as the antibody construct of the invention.

In a preferred embodiment, the bispecific antibody constructs of the invention may be linked (eg, via a peptide bond) to a fusion partner (such as a protein or polypeptide or peptide), for example, to extend the serum half-life of the construct. These fusion partners can be selected from human serum albumin (HSA or HALB) as sequence variants, HSA binding peptides, FcRn binding peptides (FcRn BP), or constructs containing (derived from an antibody) Fc region. Illustrative sequences of these fusion partners are shown in SEQ ID NOs: 780-826. In general, fusion partners can be linked to the N-terminus or C-terminus of bispecific antibody constructs of the invention, either directly (e.g. via a peptide bond) or via a peptide linker such as (GGGGS)n (where n is an integer a number equal to 2 or more, such as 2 or 3 or 4). Suitable peptide linkers are shown in SEQ ID NOs: 770-778.

Therefore, a preferred antibody construct of this invention contains:

(a) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

109 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

119 SEQ ID NO

179 SEQ ID NO

239 SEQ ID NO

299 SEQ ID NO

359 SEQ ID NO

419 SEQ ID NO

479 SEQ ID NO

539 SEQ ID NO

599 SEQ ID NO

659 SEQ ID NO

719 SEQ ID NO

934 SEQ ID NO

958 SEQ ID NO

982 SEQ ID NO

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO

1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID N O: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542,

SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NO: 770-778; and a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880,

SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919; and optionally a His-tag, such as the one shown in SEQ ID NO: 779;

(b) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

109 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

119 SEQ ID NO

179 SEQ ID NO

239 SEQ ID NO

299 SEQ ID NO

359 SEQ ID NO

419 SEQ ID NO

479 SEQ ID NO

539 SEQ ID NO

599 SEQ ID NO

659 SEQ ID NO

719 SEQ ID NO

- 24 041992

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

934 SEQ ID NO

958 SEQ ID NO

982 SEQ ID NO

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO: 1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1 360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID NO: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NO: 770-778;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880, SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919;

optionally, a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NO: 770-778;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs: 780 and 786-815; and optionally a His-tag, such as the one shown in SEQ ID NO: 779;

(c) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having the amino acid sequence QRFVTGHFGGLX1PANG (SEQ ID NO: 781) where X1 is Y or H; and a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

109 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

119 SEQ ID NO

179 SEQ ID NO

239 SEQ ID NO

299 SEQ ID NO

359 SEQ ID NO

419 SEQ ID NO

479 SEQ ID NO

539 SEQ ID NO

599 SEQ ID NO

659 SEQ ID NO

719 SEQ ID NO

934 SEQ ID NO

958 SEQ ID NO

982 SEQ ID NO

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO

1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID N O: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID

- 25 041992

NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NO: 770-778;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880,

SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919;

a polypeptide having the amino acid sequence QRFVTGHFGGLHPANG (SEQ ID NO: 783) or QRFCTGHFGGLHPCNG (SEQ ID NO: 785); and optionally a His-tag, such as the one shown in SEQ ID NO: 779;

(d) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 833, SEQ ID NO: 842, SEQ ID NO: 851, SEQ ID NO: 860, SEQ ID NO: 869, SEQ ID NO: 878,

SEQ ID NO: 887, SEQ ID NO: 896, SEQ ID NO: 905, SEQ ID NO: 914 and SEQ ID NO: 917;

a peptide linker having the amino acid sequence shown in SEQ ID NO:

777;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 18, SEQ ID NO: 28, SEQ ID NO: 38, SEQ ID NO: 48, SEQ ID NO: 58, SEQ ID

NO: 68, SEQ ID NO: 78, SEQ ID NO: 88, SEQ ID NO: 98, SEQ ID NO

128 SEQ ID NO

188 SEQ ID NO

248 SEQ ID NO

308 SEQ ID NO

368 SEQ ID NO

428 SEQ ID NO

488 SEQ ID NO

548 SEQ ID NO

608 SEQ ID NO

668 SEQ ID NO

728 SEQ ID NO

937 SEQ ID NO

961 SEQ ID NO

138 SEQ ID NO

198 SEQ ID NO

258 SEQ ID NO

318 SEQ ID NO

378 SEQ ID NO

438 SEQ ID NO

498 SEQ ID NO

558 SEQ ID NO

618 SEQ ID NO

678 SEQ ID NO

738 SEQ ID NO

941 SEQ ID NO

965 SEQ ID NO

148 SEQ ID NO

208 SEQ ID NO

268 SEQ ID NO

328 SEQ ID NO

388 SEQ ID NO

448 SEQ ID NO

508 SEQID NO

568 SEQ ID NO

628 SEQ ID NO

688 SEQ ID NO

921 SEQ ID NO

945 SEQ ID NO

969 SEQ ID NO

158 SEQ ID NO

218 SEQ ID NO

278 SEQ ID NO

338 SEQ ID NO

398 SEQ ID NO

458 SEQ ID NO

518 SEQ ID NO

578 SEQ ID NO

638 SEQ ID NO

698 SEQ ID NO

925 SEQ ID NO

949 SEQ ID NO

973 SEQ ID NO

108 SEQ ID NO

168 SEQ ID NO

228 SEQ ID NO

288 SEQ ID NO

348 SEQ ID NO

408 SEQ ID NO

468 SEQ ID NO

528 SEQ ID NO

588 SEQ ID NO

648 SEQ ID NO

708 SEQ ID NO

929 SEQ ID NO

953 SEQ ID NO

977 SEQ ID NO

118 SEQ ID NO

178 SEQ ID NO

238 SEQ ID NO

298 SEQ ID NO

358 SEQ ID NO

418 SEQ ID NO

478 SEQ ID NO

538 SEQ ID NO

598 SEQ ID NO

658 SEQ ID NO

718 SEQ ID NO

933 SEQ ID NO

957 SEQ ID NO

981 SEQ ID NO

985, SEQ ID NO: 989, SEQ ID NO: 993, SEQ ID NO: 997, SEQ ID NO: 1001, SEQ ID NO: 1005, SEQ ID NO

1009, SEQ ID NO: 1013, SEQ ID NO: 1017, SEQ ID NO: 1021, SEQ ID NO: 1025, SEQ ID NO: 1029, SEQ ID NO: 1033, SEQ ID NO: 1037, SEQ ID NO: 1041, SEQ ID NO: 1051, SEQ ID NO: 1055, SEQ ID NO: 1065, SEQ ID NO: 1069, SEQ ID NO: 1079, SEQ ID NO: 1083, SEQ ID NO: 1093, SEQ ID NO: 1097, SEQ ID NO: 1107, SEQ ID NO: 1111, SEQ ID NO: 1121, SEQ ID NO: 1125, SEQ ID NO: 1135, SEQ ID NO: 1139, SEQ ID NO: 1149, SEQ ID NO: 1153, SEQ ID NO: 1163, SEQ ID NO: 1167, SEQ ID NO: 1177, SEQ ID NO: 1181, SEQ ID NO: 1191, SEQ ID NO: 1195, SEQ ID NO: 1205, SEQ ID NO: 1209, SEQ ID NO: 1219, SEQ ID NO: 1223, SEQ ID NO: 1233, SEQ ID NO: 1237, SEQ ID NO: 1247, SEQ ID NO: 1251, SEQ ID NO: 1261, SEQ ID NO: 1265, SEQ ID NO: 1275, SEQ ID NO: 1279, SEQ ID NO: 1289, SEQ ID NO: 1293, SEQ ID NO: 1303, SEQ ID NO: 1307, SEQ ID NO: 1317, SEQ ID NO: 1321, SEQ ID NO: 1331, SEQ ID NO: 1335, SEQ ID NO: 1345, SEQ ID NO: 1349, SEQ ID NO: 1359, SEQ ID NO: 1363, SEQ ID NO: 1373, SEQ ID NO: 1377, SEQ ID NO: 1387, SEQ ID NO: 1391, SEQ ID N O: 1401, SEQ ID NO: 1405, SEQ ID NO: 1415, SEQ ID NO: 1419, SEQ ID NO: 1429, SEQ ID NO: 1433, SEQ ID NO: 1443, SEQ ID NO: 1447, SEQ ID NO: 1457, SEQ ID NO: 1461, SEQ ID NO: 1471, SEQ ID NO: 1475, SEQ ID NO: 1485, SEQ ID NO: 1489, SEQ ID NO: 1499, SEQ ID NO: 1503, SEQ ID NO: 1513, SEQ ID NO: 1517, SEQ ID NO: 1527, SEQ ID NO: 1531, SEQ ID NO: 1541, SEQ ID NO: 1545, SEQ ID NO: 1555, SEQ ID NO: 1559, SEQ ID NO: 1569 and SEQ ID NO: 1573, followed by a serine residue at the C-terminus;

a polypeptide having the amino acid sequence shown in SEQ ID NO: 816; and a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID

NO: 67, SEQ ID NO: 77, SEQ ID NO: 87, SEQ ID NO: 97, SEQ ID NO

127, SEQ ID NO 187, SEQ ID NO 247, SEQ ID NO 307, SEQ ID NO 367, SEQ ID NO 427, SEQ ID NO 487, SEQ ID NO

547 SEQ ID NO

137 SEQ ID NO

197 SEQ ID NO

257 SEQ ID NO

317 SEQ ID NO

377 SEQ ID NO

437 SEQ ID NO

497 SEQ ID NO

557 SEQ ID NO

147 SEQ ID NO

207 SEQ ID NO

267 SEQ ID NO

327 SEQ ID NO

387 SEQ ID NO

447 SEQ ID NO

507 SEQ ID NO

567 SEQ ID NO

157 SEQ ID NO

217 SEQ ID NO

277 SEQ ID NO

337 SEQ ID NO

397 SEQ ID NO

457 SEQ ID NO

517 SEQ ID NO

577 SEQ ID NO

107 SEQ ID NO

167 SEQ ID NO

227 SEQ ID NO

287 SEQ ID NO

347 SEQ ID NO

407 SEQ ID NO

467 SEQ ID NO

527 SEQ ID NO

587 SEQ ID NO

117 SEQ ID NO

177 SEQ ID NO

237 SEQ ID NO

297 SEQ ID NO

357 SEQ ID NO

417 SEQ ID NO

477 SEQ ID NO

537 SEQ ID NO

597 SEQ ID NO

- 26 041992

607, SEQ ID NO: 617, SEQ ID NO: 627, SEQ ID NO: 637, SEQ ID NO: 647, SEQ ID NO: 657, SEQ ID NO:

667, SEQ ID NO: 677, SEQ ID NO: 687, SEQ ID NO: 697, SEQ ID NO: 707, SEQ ID NO: 717, SEQ ID NO:

727, SEQ ID NO: 737, SEQ ID NO: 920, SEQ ID NO: 924, SEQ ID NO: 928, SEQ ID NO: 932, SEQ ID NO:

936, SEQ ID NO: 940, SEQ ID NO: 944, SEQ ID NO: 948, SEQ ID NO: 952, SEQ ID NO: 956, SEQ ID NO:

960, SEQ ID NO: 964, SEQ ID NO: 968, SEQ ID NO: 972, SEQ ID NO: 976, SEQ ID NO: 980, SEQ ID NO:

984, SEQ ID NO: 988, SEQ ID NO: 992, SEQ ID NO: 996, SEQ ID NO: 1000, SEQ ID NO: 1004, SEQ ID NO: 1008, SEQ ID NO: 1012, SEQ ID NO: 1016, SEQ ID NO: 1020, SEQ ID NO: 1024, SEQ ID NO: 1028, SEQ ID NO: 1032, SEQ ID NO: 1036, SEQ ID NO: 1040, SEQ ID NO: 1050, SEQ ID NO: 1054, SEQ ID NO: 1064, SEQ ID NO: 1068, SEQ ID NO: 1078, SEQ ID NO: 1082, SEQ ID NO: 1092, SEQ ID NO: 1096, SEQ ID NO: 1106, SEQ ID NO: 1110, SEQ ID NO: 1120, SEQ ID NO: 1124, SEQ ID NO: 1134, SEQ ID NO: 1138, SEQ ID NO: 1148, SEQ ID NO: 1152, SEQ ID NO: 1162, SEQ ID NO: 1166, SEQ ID NO: 1176, SEQ ID NO: 1180, SEQ ID NO: 1190, SEQ ID NO: 1194, SEQ ID NO: 1204, SEQ ID NO: 1208, SEQ ID NO: 1218, SEQ ID NO: 1222, SEQ ID NO: 1232, SEQ ID NO: 1236, SEQ ID NO: 1246, SEQ ID NO: 1250, SEQ ID NO: 1260, SEQ ID NO: 1264, SEQ ID NO: 1274, SEQ ID NO: 1278, SEQ ID NO: 1288, SEQ ID NO: 1292, SEQ ID NO: 1302, SEQ ID NO: 1306, SEQ ID NO: 1316, SEQ ID NO: 1320, SEQ ID NO: 1330, SEQ ID NO: 1334, SEQ ID NO: 1344, SEQ ID NO: 1348, SEQ ID NO: 1 358, SEQ ID NO: 1362, SEQ ID NO: 1372, SEQ ID NO: 1376, SEQ ID NO: 1386, SEQ ID NO: 1390, SEQ ID NO: 1400, SEQ ID NO: 1404, SEQ ID NO: 1414, SEQ ID NO: 1418, SEQ ID NO: 1428, SEQ ID NO: 1432, SEQ ID NO: 1442, SEQ ID NO: 1446, SEQ ID NO: 1456, SEQ ID NO: 1460, SEQ ID NO: 1470, SEQ ID NO: 1474, SEQ ID NO: 1484, SEQ ID NO: 1488, SEQ ID NO: 1498, SEQ ID NO: 1502, SEQ ID NO: 1512, SEQ ID NO: 1516, SEQ ID NO: 1526, SEQ ID NO: 1530, SEQ ID NO: 1540, SEQ ID NO: 1544, SEQ ID NO: 1554, SEQ ID NO: 1558, SEQ ID NO: 1568 and SEQ ID NO: 1572;

a peptide linker having the amino acid sequence shown in SEQ ID NO: 777;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 834, SEQ ID NO: 843, SEQ ID NO: 852, SEQ ID NO: 861, SEQ ID NO: 870, SEQ ID NO: 879, SEQ ID NO: 888, SEQ ID NO: 897, SEQ ID NO: 906, SEQ ID NO: 915 and SEQ ID NO: 918, followed by a serine residue at the C-terminus; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 817;

(e) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 833, SEQ ID NO: 842, SEQ ID NO: 851, SEQ ID NO: 860, SEQ ID NO: 869, SEQ ID NO: 878,

SEQ ID NO: 887, SEQ ID NO: 896, SEQ ID NO: 905, SEQ ID NO: 914 and SEQ ID NO: 917;

777;

a peptide linker having the amino acid sequence shown in SEQ ID NO:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 8, SEQ ID NO: 18, SEQ ID NO: 28, SEQ ID NO: 38, SEQ ID NO: 48, SEQ ID NO: 58, SEQ ID

NO: 68, SEQ ID NO: 78, SEQ ID NO: 88, SEQ ID NO: 98, SEQ ID NO

128 SEQ ID NO

188 SEQ ID NO

248 SEQ ID NO

308 SEQ ID NO

368 SEQ ID NO

428 SEQ ID NO

488 SEQ ID NO

548 SEQ ID NO

608 SEQ ID NO

668 SEQ ID NO

728 SEQ ID NO

937 SEQ ID NO

961 SEQ ID NO

138 SEQ ID NO

198 SEQ ID NO

258 SEQ ID NO

318 SEQ ID NO

378 SEQ ID NO

438 SEQ ID NO

498 SEQ ID NO

558 SEQ ID NO

618 SEQ ID NO

678 SEQ ID NO

738 SEQ ID NO

941 SEQ ID NO

965 SEQ ID NO

148 SEQ ID NO

208 SEQ ID NO

268 SEQ ID NO

328 SEQ ID NO

388 SEQ ID NO

448 SEQ ID NO

508 SEQID NO

568 SEQ ID NO

628 SEQ ID NO

688 SEQ ID NO

921 SEQ ID NO

945 SEQ ID NO

969 SEQ ID NO

158 SEQ ID NO

218 SEQ ID NO

278 SEQ ID NO

338 SEQ ID NO

398 SEQ ID NO

458 SEQ ID NO

518 SEQ ID NO

578 SEQ ID NO

638 SEQ ID NO

698 SEQ ID NO

925 SEQ ID NO

949 SEQ ID NO

973 SEQ ID NO

108 SEQ ID NO

168 SEQ ID NO

228 SEQ ID NO

288 SEQ ID NO

348 SEQ ID NO

408 SEQ ID NO

468 SEQ ID NO

528 SEQ ID NO

588 SEQ ID NO

648 SEQ ID NO

708 SEQ ID NO

929 SEQ ID NO

953 SEQ ID NO

977 SEQ ID NO

118, SEQ ID NO 178, SEQ ID NO 238, SEQ ID NO 298, SEQ ID NO 358, SEQ ID NO 418, SEQ ID NO 478, SEQ ID NO 538, SEQ ID NO 598, SEQ ID NO 658, SEQ ID NO 718, SEQ ID NO 933, SEQ ID NO 957, SEQ ID NO 981, SEQ ID NO

985, SEQ ID NO: 989, SEQ ID NO: 993, SEQ ID NO: 997, SEQ ID NO: 1001, SEQ ID NO: 1005, SEQ ID NO

1009, SEQ ID NO: 1013, SEQ ID NO: 1017, SEQ ID NO: 1021, SEQ ID NO: 1025, SEQ ID NO: 1029, SEQ ID NO: 1033, SEQ ID NO: 1037, SEQ ID NO: 1041, SEQ ID NO: 1051, SEQ ID NO: 1055, SEQ ID NO: 1065, SEQ ID NO: 1069, SEQ ID NO: 1079, SEQ ID NO: 1083, SEQ ID NO: 1093, SEQ ID NO: 1097, SEQ ID NO: 1107, SEQ ID NO: 1111, SEQ ID NO: 1121, SEQ ID NO: 1125, SEQ ID NO: 1135, SEQ ID NO: 1139, SEQ ID NO: 1149, SEQ ID NO: 1153, SEQ ID NO: 1163, SEQ ID NO: 1167, SEQ ID NO: 1177, SEQ ID NO: 1181, SEQ ID NO: 1191, SEQ ID NO: 1195, SEQ ID NO: 1205, SEQ ID NO: 1209, SEQ ID NO: 1219, SEQ ID NO: 1223, SEQ ID NO: 1233, SEQ ID NO: 1237, SEQ ID NO: 1247, SEQ ID NO: 1251, SEQ ID NO: 1261, SEQ ID NO: 1265, SEQ ID NO: 1275, SEQ ID NO: 1279, SEQ ID NO: 1289, SEQ ID NO: 1293, SEQ ID NO: 1303, SEQ ID NO: 1307, SEQ ID NO: 1317, SEQ ID NO: 1321, SEQ ID NO: 1331, SEQ ID NO: 1335, SEQ ID NO: 1345, SEQ ID NO: 1349, SEQ ID NO: 1359, SEQ ID NO: 1363, SEQ ID NO: 1373, SEQ ID NO: 1377, SEQ ID NO: 1387, SEQ ID NO: 1391, SEQ ID N O: 1401, SEQ ID NO: 1405, SEQ ID NO: 1415, SEQ ID NO: 1419,

- 27 041992

SEQ ID NO: 1429, SEQ ID NO: 1433, SEQ ID NO: 1443, SEQ ID NO: 1447, SEQ ID NO: 1457, SEQ ID NO: 1461, SEQ ID NO: 1471, SEQ ID NO: 1475, SEQ ID NO: 1485, SEQ ID NO: 1489, SEQ ID NO: 1499, SEQ ID NO: 1503, SEQ ID NO: 1513, SEQ ID NO: 1517, SEQ ID NO: 1527, SEQ ID NO: 1531, SEQ ID NO: 1541, SEQ ID NO: 1545, SEQ ID NO: 1555, SEQ ID NO: 1559, SEQ ID NO: 1569 and SEQ ID NO: 1573; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 818; and a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID

NO: 67, SEQ ID NO: 77, SEQ ID NO: 87, SEQ ID NO: 97, SEQ ID NO

127 SEQ ID NO

187 SEQ ID NO

247 SEQ ID NO

307 SEQ ID NO

367 SEQ ID NO

427 SEQ ID NO

487 SEQ ID NO

547 SEQ ID NO

607 SEQ ID NO

667 SEQ ID NO

727 SEQ ID NO

936 SEQ ID NO

960 SEQ ID NO

137 SEQ ID NO

197 SEQ ID NO

257 SEQ ID NO

317 SEQ ID NO

377 SEQ ID NO

437 SEQ ID NO

497 SEQ ID NO

557 SEQ ID NO

617 SEQ ID NO

677 SEQ ID NO

737 SEQ ID NO

940 SEQ ID NO

964 SEQ ID NO

147 SEQ ID NO

207 SEQ ID NO

267 SEQ ID NO

327 SEQ ID NO

387 SEQ ID NO

447 SEQ ID NO

507 SEQ ID NO

567 SEQ ID NO

627 SEQ ID NO

687 SEQ ID NO

920 SEQ ID NO

944 SEQ ID NO

968 SEQ ID NO

157 SEQ ID NO

217 SEQ ID NO

277 SEQ ID NO

337 SEQ ID NO

397 SEQ ID NO

457 SEQ ID NO

517 SEQ ID NO

577 SEQ ID NO

637 SEQ ID NO

697 SEQ ID NO

924 SEQ ID NO

948 SEQ ID NO

972 SEQ ID NO

107 SEQ ID NO

167 SEQ ID NO

227 SEQ ID NO

287 SEQ ID NO

347 SEQ ID NO

407 SEQ ID NO

467 SEQ ID NO

527 SEQ ID NO

587 SEQ ID NO

647 SEQ ID NO

707 SEQ ID NO

928 SEQ ID NO

952 SEQ ID NO

976 SEQ ID NO

117 SEQ ID NO

177 SEQ ID NO

237 SEQ ID NO

297 SEQ ID NO

357 SEQ ID NO

417 SEQ ID NO

477 SEQ ID NO

537 SEQ ID NO

597 SEQ ID NO

657 SEQ ID NO

717 SEQ ID NO

932 SEQ ID NO

956 SEQ ID NO

980 SEQ ID NO

984, SEQ ID NO: 988, SEQ ID NO: 992, SEQ ID NO: 996, SEQ ID NO: 1000, SEQ ID NO: 1004, SEQ ID NO: 1008, SEQ ID NO: 1012, SEQ ID NO: 1016, SEQ ID NO: 1020, SEQ ID NO: 1024, SEQ ID NO: 1028, SEQ ID NO: 1032, SEQ ID NO: 1036, SEQ ID NO: 1040, SEQ ID NO: 1050, SEQ ID NO: 1054, SEQ ID NO: 1064, SEQ ID NO: 1068, SEQ ID NO: 1078, SEQ ID NO: 1082, SEQ ID NO: 1092, SEQ ID NO: 1096, SEQ ID NO: 1106, SEQ ID NO: 1110, SEQ ID NO: 1120, SEQ ID NO: 1124, SEQ ID NO: 1134, SEQ ID NO: 1138, SEQ ID NO: 1148, SEQ ID NO: 1152, SEQ ID NO: 1162, SEQ ID NO: 1166, SEQ ID NO: 1176, SEQ ID NO: 1180, SEQ ID NO: 1190, SEQ ID NO: 1194, SEQ ID NO: 1204, SEQ ID NO: 1208, SEQ ID NO: 1218, SEQ ID NO: 1222, SEQ ID NO: 1232, SEQ ID NO: 1236, SEQ ID NO: 1246, SEQ ID NO: 1250, SEQ ID NO: 1260, SEQ ID NO: 1264, SEQ ID NO: 1274, SEQ ID NO: 1278, SEQ ID NO: 1288, SEQ ID NO: 1292, SEQ ID NO: 1302, SEQ ID NO: 1306, SEQ ID NO: 1316, SEQ ID NO: 1320, SEQ ID NO: 1330, SEQ ID NO: 1334, SEQ ID NO: 1344, SEQ ID NO: 1348, SEQ ID NO: 1 358, SEQ ID NO: 1362, SEQ ID NO: 1372, SEQ ID NO: 1376, SEQ ID NO: 1386, SEQ ID NO: 1390, SEQ ID NO: 1400, SEQ ID NO: 1404, SEQ ID NO: 1414, SEQ ID NO: 1418, SEQ ID NO: 1428, SEQ ID NO: 1432, SEQ ID NO: 1442, SEQ ID NO: 1446, SEQ ID NO: 1456, SEQ ID NO: 1460, SEQ ID NO: 1470, SEQ ID NO: 1474, SEQ ID NO: 1484, SEQ ID NO: 1488, SEQ ID NO: 1498, SEQ ID NO: 1502, SEQ ID NO: 1512, SEQ ID NO: 1516, SEQ ID NO: 1526, SEQ ID NO: 1530, SEQ ID NO: 1540, SEQ ID NO: 1544, SEQ ID NO: 1554, SEQ ID NO: 1558, SEQ ID NO: 1568 and SEQ ID NO: 1572;

a peptide linker having the amino acid sequence shown in SEQ ID NO: 777;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 834, SEQ ID NO: 843, SEQ ID NO: 852, SEQ ID NO: 861, SEQ ID NO: 870, SEQ ID NO: 879, SEQ ID NO: 888, SEQ ID NO: 897, SEQ ID NO: 906, SEQ ID NO: 915 and SEQ ID NO: 918, followed by a serine residue at the C-terminus; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 819;

(f) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO

129, SEQ ID NO 189, SEQ ID NO 249, SEQ ID NO 309, SEQ ID NO 369, SEQ ID NO 429, SEQ ID NO 489, SEQ ID NO 549, SEQ ID NO 609, SEQ ID NO 669, SEQ ID NO 729, SEQ ID NO 938, SEQ ID NO 962, SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

109 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

119 SEQ ID NO

179 SEQ ID NO

239 SEQ ID NO

299 SEQ ID NO

359 SEQ ID NO

419 SEQ ID NO

479 SEQ ID NO

539 SEQ ID NO

599 SEQ ID NO

659 SEQ ID NO

719 SEQ ID NO

934 SEQ ID NO

958 SEQ ID NO

982 SEQ ID NO

- 28 041992

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO: 1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1 360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID NO: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542,

SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NO: 770-778;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880,

SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919;

a polypeptide having the amino acid sequence shown in SEQ ID NO: 820; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 821;

(g) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO: 109, SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

119 SEQ ID NO

179 SEQ ID NO

239 SEQ ID NO

299 SEQ ID NO

359 SEQ ID NO

419 SEQ ID NO

479 SEQ ID NO

539 SEQ ID NO

599 SEQ ID NO

659 SEQ ID NO

719 SEQ ID NO

934 SEQ ID NO

958 SEQ ID NO

982 SEQ ID NO

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO

1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID N O: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 822; and a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880, SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 823;

- 29 041992 (h) a polypeptide containing in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

109 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

119, SEQ ID NO 179, SEQ ID NO 239, SEQ ID NO 299, SEQ ID NO 359, SEQ ID NO 419, SEQ ID NO 479, SEQ ID NO 539, SEQ ID NO 599, SEQ ID NO 659, SEQ ID NO 719, SEQ ID NO 934, SEQ ID NO 958, SEQ ID NO 982, SEQ ID NO

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO

1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID N O: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 824; and a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880, SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 825;

or (i) a polypeptide containing, in the following order, starting from the N-terminus:

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID

NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO

129 SEQ ID NO

189 SEQ ID NO

249 SEQ ID NO

309 SEQ ID NO

369 SEQ ID NO

429 SEQ ID NO

489 SEQ ID NO

549 SEQ ID NO

609 SEQ ID NO

669 SEQ ID NO

729 SEQ ID NO

938 SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159 SEQ ID NO

219 SEQ ID NO

279 SEQ ID NO

339 SEQ ID NO

399 SEQ ID NO

459 SEQ ID NO

519 SEQ ID NO

579 SEQ ID NO

639 SEQ ID NO

699 SEQ ID NO

926 SEQ ID NO

950 SEQ ID NO

974 SEQ ID NO

109 SEQ ID NO

169 SEQ ID NO

229 SEQ ID NO

289 SEQ ID NO

349 SEQ ID NO

409 SEQ ID NO

469 SEQ ID NO

529 SEQ ID NO

589 SEQ ID NO

649 SEQ ID NO

709 SEQ ID NO

930 SEQ ID NO

954 SEQ ID NO

978 SEQ ID NO

119, SEQ ID NO 179, SEQ ID NO 239, SEQ ID NO 299, SEQ ID NO 359, SEQ ID NO 419, SEQ ID NO 479, SEQ ID NO 539, SEQ ID NO 599, SEQ ID NO 659, SEQ ID NO 719, SEQ ID NO 934, SEQ ID NO 958, SEQ ID NO 982, SEQ ID NO

986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO: 1006, SEQ ID NO

1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID

- 30 041992

NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID NO: 1392, SEQ ID NO: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556 SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NO: 770-778;

a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880, SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919; and a polypeptide having the amino acid sequence shown in SEQ ID NO: 826.

As described above, several preferred antibody constructs of the invention are modified by fusion with another moiety, such as albumin or albumin variants. If these fusion constructs are characterized by their properties, such as, in particular, their target affinity or cytotoxic activity, the person skilled in the art will know that such fusion constructs or unmodified bispecific antibody constructs may have similar (or perhaps even better) properties. For example, if a bispecific antibody structure fused to albumin has significant or desirable cytotoxic activity or target affinity, one would expect the same construct to be observed at the same/similar or even higher cytotoxic activity/target affinity. without albumin.

In accordance with another preferred embodiment of the invention, the bispecific antibody construct of the invention contains (in addition to the two binding domains) a third domain that contains two polypeptide monomers, each containing a hinge, a CH2 and a CH3 domain, said two polypeptides (or polypeptides monomers) fused to each other via a peptide linker. Preferably, said third domain comprises, in the N-C terminal order: hinge-CH2-CH3-linker-hinge-CH2-CH3. Preferred amino acid sequences for this third domain are shown in SEQ ID NOs: 1856-1863. Each of these polypeptide monomers preferably has an amino acid sequence selected from the group consisting of SEQ ID NO: 1848-1855, or at least 90% identical to these sequences. In another preferred embodiment of the invention, the first and second binding domains of the bispecific antibody construct of the invention are fused to the third domain via a peptide linker which, for example, is selected from the group consisting of SEQ ID NOs: 770, 771, 773, 774, 775, 777 and 778.

In accordance with the present invention, the hinge is an IgG hinge region. This area can be identified by analogy using Kabat numbering, see Kabat entries 223-243. According to the above, the minimum requirement for a hinge is amino acid residues corresponding to the IgG1 sequence region D231 to P243 according to Kabat numbering. The terms CH2 and CH3 refer to constant regions 2 and 3 of an immunoglobulin heavy chain. These regions can also be identified by analogy using Rabat numbering, see Rabat entries 244-360 for CH2 and Rabat entries 361-478 for CH3. It is understood that there is some variation between immunoglobulins between their IgG1 Fc region, IgG ₂ Fc region, IgG ₃ Fc region, IgG ₄ Fc region, IgM Fc region, IgA Fc region, IgD Fc region, and IgE Fc region (see, for example, Padlan, Molecular Immunology, 31 (3), 169-217 (1993)). The term Fc monomer refers to the last two IgA heavy chain constant regions, IgD and IgG, and the last three IgE and IgM heavy chain constant regions. The Fc monomer may also contain a flexible hinge at the N-terminus of these domains. For IgA and IgM, the Fc monomer may contain a J chain. In IgG, the Fc portion contains the immunoglobulin domains CH2 and CH3 and a hinge between the first two domains and CH2. Although the boundaries of the Fc portion of an immunoglobulin may vary, an example for a human IgG heavy chain Fc portion containing a functional hinge, a CH2 domain, and a CH3 domain can be defined, for example, as containing residues D231 (the hinge domain) to P476 (the C-terminus of the domain CH3) or respectively from D231 to L476 for IgG ₄ where the numbering corresponds to Kabat.

An antibody construct of the invention may therefore contain, in order from N- to C-terminus:

(a) a first binding domain;

(b) a peptide linker having an amino acid sequence selected from the group co-

- 31 041992 standing for SEQ ID NOs: 771, 777 and 778;

(c) a second binding domain;

(d) a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NOs: 770, 771, 773, 774, 775, 777 and 778;

(e) a first third domain polypeptide monomer (comprising a hinge, CH2, and a CH3 domain);

(f) a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1865, 1866, 1867 and 1868; and (g) a second third domain polypeptide monomer (comprising a hinge, CH2, and a CH3 domain);

It is also preferred that the antibody construct of the invention contains, in order from N to C-terminus:

the first binding domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 19, SEQ ID NO: 29, SEQ ID NO: 39, SEQ ID NO: 49, SEQ ID

NO: 59, SEQ ID NO: 69, SEQ ID NO: 79, SEQ ID NO: 89, SEQ ID NO: 99, SEQ ID NO: 109, SEQ ID NO

119, SEQ ID NO 179, SEQ ID NO 239, SEQ ID NO 299, SEQ ID NO

359, SEQ ID NO 419, SEQ ID NO 479, SEQ ID NO 539, SEQ ID NO 599, SEQ ID NO

659, SEQ ID NO 719, SEQ ID NO 934, SEQ ID NO 958, SEQ ID NO

129, SEQ ID NO 189, SEQ ID NO 249, SEQ ID NO 309, SEQ ID NO 369, SEQ ID NO 429, SEQ ID NO

489, SEQ ID NO 549, SEQ ID NO 609, SEQ ID NO 669, SEQ ID NO 729, SEQ ID NO 938, SEQ ID NO

962 SEQ ID NO

139 SEQ ID NO

199 SEQ ID NO

259 SEQ ID NO

319 SEQ ID NO

379 SEQ ID NO

439 SEQ ID NO

499 SEQ ID NO

559 SEQ ID NO

619 SEQ ID NO

679 SEQ ID NO

739 SEQ ID NO

942 SEQ ID NO

966 SEQ ID NO

149 SEQ ID NO

209 SEQ ID NO

269 SEQ ID NO

329 SEQ ID NO

389 SEQ ID NO

449 SEQ ID NO

509 SEQ ID NO

569 SEQ ID NO

629 SEQ ID NO

689 SEQ ID NO

922 SEQ ID NO

946 SEQ ID NO

970 SEQ ID NO

159, SEQ ID NO 219, SEQ ID NO 279, SEQ ID NO 339, SEQ ID NO 399, SEQ ID NO 459, SEQ ID NO 519, SEQ ID NO 579, SEQ ID NO

639, SEQ ID NO 699, SEQ ID NO 926, SEQ ID NO 950, SEQ ID NO 974, SEQ ID NO

169, SEQ ID NO 229, SEQ ID NO 289, SEQ ID NO 349, SEQ ID NO 409, SEQ ID NO 469, SEQ ID NO

529, SEQ ID NO 589, SEQ ID NO 649, SEQ ID NO 709, SEQ ID NO 930, SEQ ID NO 954, SEQ ID NO

978 SEQ ID NO

982, SEQ ID NO: 986, SEQ ID NO: 990, SEQ ID NO: 994, SEQ ID NO: 998, SEQ ID NO: 1002, SEQ ID NO

1006, SEQ ID NO: 1010, SEQ ID NO: 1014, SEQ ID NO: 1018, SEQ ID NO: 1022, SEQ ID NO: 1026, SEQ ID NO: 1030, SEQ ID NO: 1034, SEQ ID NO: 1038, SEQ ID NO: 1042, SEQ ID NO: 1052, SEQ ID NO: 1056, SEQ ID NO: 1066, SEQ ID NO: 1070, SEQ ID NO: 1080, SEQ ID NO: 1084, SEQ ID NO: 1094, SEQ ID NO: 1098, SEQ ID NO: 1108, SEQ ID NO: 1112, SEQ ID NO: 1122, SEQ ID NO: 1126, SEQ ID NO: 1136, SEQ ID NO: 1140, SEQ ID NO: 1150, SEQ ID NO: 1154, SEQ ID NO: 1164, SEQ ID NO: 1168, SEQ ID NO: 1178, SEQ ID NO: 1182, SEQ ID NO: 1192, SEQ ID NO: 1196, SEQ ID NO: 1206, SEQ ID NO: 1210, SEQ ID NO: 1220, SEQ ID NO: 1224, SEQ ID NO: 1234, SEQ ID NO: 1238, SEQ ID NO: 1248, SEQ ID NO: 1252, SEQ ID NO: 1262, SEQ ID NO: 1266, SEQ ID NO: 1276, SEQ ID NO: 1280, SEQ ID NO: 1290, SEQ ID NO: 1294, SEQ ID NO: 1304, SEQ ID NO: 1308, SEQ ID NO: 1318, SEQ ID NO: 1322, SEQ ID NO: 1332, SEQ ID NO: 1336, SEQ ID NO: 1346, SEQ ID NO: 1350, SEQ ID NO: 1360, SEQ ID NO: 1364, SEQ ID NO: 1374, SEQ ID NO: 1378, SEQ ID NO: 1388, SEQ ID N O: 1392, SEQ ID NO: 1402, SEQ ID NO: 1406, SEQ ID NO: 1416, SEQ ID NO: 1420, SEQ ID NO: 1430, SEQ ID NO: 1434, SEQ ID NO: 1444, SEQ ID NO: 1448, SEQ ID NO: 1458, SEQ ID NO: 1462, SEQ ID NO: 1472, SEQ ID NO: 1476, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1500, SEQ ID NO: 1504, SEQ ID NO: 1514, SEQ ID NO: 1518, SEQ ID NO: 1528, SEQ ID NO: 1532, SEQ ID NO: 1542, SEQ ID NO: 1546, SEQ ID NO: 1556, SEQ ID NO: 1560, SEQ ID NO: 1570 and SEQ ID NO: 1574;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NOs: 771, 777 and 778;

a second binding domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 835, SEQ ID NO: 844, SEQ ID NO: 853, SEQ ID NO: 862, SEQ ID NO: 871, SEQ ID NO: 880, SEQ ID NO: 889, SEQ ID NO: 898, SEQ ID NO: 907, SEQ ID NO: 916 and SEQ ID NO: 919;

a peptide linker having an amino acid sequence selected from the group consisting of SEQ ID NOs: 770, 771, 773, 774, 775, 777 and 778; and a third domain having an amino acid sequence selected from the group consisting of SEQ ID NO: 1856-1863.

Therefore, in a preferred embodiment, the antibody construct of the invention comprises or consists of a polypeptide selected from the group consisting of those shown in SEQ ID NOs: 1576-1847. Preferred are those polypeptides selected from the group consisting of those shown in SEQ ID NO: 1696, SEQ ID NO: 1702, SEQ ID NO: 1710, SEQ ID NO: 1714, SEQ ID NO: 1716, SEQ ID NO : 1720, SEQ ID NO: 1722, SEQ ID NO: 1724, SEQ ID NO: 1726, SEQ ID NO: 1728, SEQ ID NO: 1738, SEQ ID NO: 1740, SEQ ID NO: 1742, SEQ ID NO: 1750 and SEQ ID NO: 1752.

Covalent modifications of antibody constructs are also included within the scope of this invention and are usually, but not always, performed post-translationally. For example, several types of covalent modifications to the antibody construct are introduced into the molecule by reacting specific amino acid residues of the antibody construct with an organic derivatizing agent that is capable of reacting with selected N- or C-terminal side chains.

Cysteinyl residues are most commonly reacted with α-haloacetates (and the corresponding amines) such as chloroacetic acid or chloroacetamide to give carboxymethyl or carboxyamidomethyl derivatives.

Cysteinyl residues are also derivatized by reaction with bromotrifluoroacetone, α-bromos-(5-imidozoyl) propionic acid, chloroacetyl phosphate, N-alkylmaleimides, 3-nitro-2-pyridyl disulfide, methyl-2-pyridyl disulfide, p-chloromercury benzoate, 2-chloromercury-4 -nitrophenol or chloro-7-nitrobenzo-2-oxa-1,3-diazole.

Histidyl residues are derivatized by reaction with diethyl pyrocarbonate at pH 5.5-7.0 because this agent is relatively specific for the histidyl side chain. Para-bromophenacyl bromide is also applicable; the reaction is preferably carried out in a 0.1 M solution of sodium cacodylate at pH 6.0. Lysinyl and amino-terminal residues are reacted with succinic anhydride or anhydrides of other carboxylic acids. Derivatization with these agents can lead to a change in the charge of lysinyl residues. Other suitable reagents for derivatizing alpha-amino residues include imidoesters such as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride; trinitrobenzenesulfonic acid; O-methylisourea; 2,4pentanedione; and a transaminase-catalyzed reaction with glyoxylate.

Arginyl residues are modified by reaction with one or more conventional reagents, including phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione, and ninhydrin. Derivatization of arginine residues requires that the reaction be carried out in an alkaline environment due to the high pKa of the guanidine functional group. In addition, such reagents can interact with lysine groups, as well as with the arginine epsilon-amino group.

Specific modifications of tyrosyl residues can be carried out, of particular interest are the cases of introducing spectral labels into tyrosyl residues by reaction with aromatic diazonium compounds or tetranitromethane. The most commonly used are N-acetylimidizole and tetranitromethane for the formation of O-acetyl tyrosyl and 3-nitro derivatives, respectively. Tyrosyl residues are iodinated using ¹²⁵ I or ¹³¹ I to obtain labeled proteins for use in radioimmunoassay, the chloramine T method described above being suitable.

Carboxyl side groups (aspartyl or glutamyl) are selectively modified by reaction with carbodiimides (R'-N=C=N--R'), where R and R' are optionally different alkyl groups such as 1-cyclohexyl-3- (2-morpholinyl-4-ethyl)carbodiimide or 1-ethyl-3-(4-azonia4,4-dimethylphenyl)carbodiimide. In addition, aspartyl and glutamyl residues are converted to asparaginyl and glutaminyl residues by reaction with ammonium ions.

Derivatization with bifunctional agents is used to cross-link antibody constructs of this invention with a water-insoluble matrix substrate or surface for use in various methods. Commonly used cross-linking agents include, for example, 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters, such as 3,3 '-dithio-bis-(succinimidyl propionate), and bifunctional maleimides such as bis-N-maleimido-1,8-octane. Using derivatizing agents such as methyl 3-[(p-azidophenyl)dithio]propioimidate, photoactivated intermediates are obtained which are capable of forming crosslinks in the presence of light. Alternatively, water-insoluble matrices such as cyanogen bromide-activated carbohydrates and reactive substrates are used to immobilize the protein, as described in US Pat. Nos. 3,969,287; 3691016; 4195128; 4247642; 4229537 and 4330440.

The glutaminyl and asparaginyl residues are often deamidated to the corresponding glutamyl and aspartyl residues, respectively. Alternatively, these residues are deamidated under moderately acidic conditions. Any form of these residues is within the scope of this invention.

Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of α-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, 1983, pp. 79-86), acetylation of the N-terminal amine and amidation of any C-terminal carboxyl group.

Another type of covalent modification of antibody constructs that is within the scope of this invention involves altering the glycosylation profile of a protein. As is known in the art, glycosylation profiles can depend both on the sequence of the protein (eg, the presence or absence of specific glycosylation amino acid residues discussed below) and on the host cell or organism in which the protein is produced. Specific expression systems are discussed below.

Glycosylation of polypeptides is typically N-linked or O-linked. N-linked

- 33 041992 Glycosylation refers to the attachment of a carbohydrate group to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, represent recognition sequences for enzymatic attachment of a carbohydrate component to the asparagine side chain. Therefore, the presence of any of these tripeptide sequences creates a potential glycosylation site. O-linked glycosylation refers to the addition of one of the sugars N-acetylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine can also be used.

The addition of glycosylation sites to the disclosed antibody construct is conveniently accomplished by changing the amino acid sequence to include one or more of the tripeptide sequences described above (for N-linked glycosylation sites). The change can also be made by adding or substituting one or more serine or threonine residues in the original sequence (for O-linked glycosylation sites). For convenience, the amino acid sequence of the antibody construct is preferably changed at the DNA level, in particular by mutating the DNA encoding the target polypeptide at preselected bases so that the generated codons are translated into the required amino acids.

Another way to increase the number of carbohydrate components in an antibody construct is to chemically or enzymatically couple glycosides to a protein. These procedures are advantageous because they do not require the production of a host cell protein that is capable of N- or O-linked glycosylation. Depending on the coupling method used, the sugar(s) may be attached to (a) arginine and histidine, (b) free carboxyl groups, (c) free sulfhydryl groups such as cysteine sulfhydryl groups, (d) free hydroxyl groups such as as hydroxyl groups of serine, threonine or hydroxyproline, (e) aromatic residues such as aromatic residues of phenylalanine, tyrosine or tryptophan or (f) glutamine amide group. These methods are described in WO 87/05330, and Aplin and Wriston, 1981, CRC Crit. Rev. Biochem., p. 259-306.

Removal of carbohydrate residues present in the original antibody construct may be carried out chemically or enzymatically. For chemical deglycosylation, it is necessary to expose the protein to the action of a trifluoromethanesulfonic acid compound or an equivalent compound. This treatment results in cleavage of most or all of the Sugars except the linking sugar (N-acetylglucosamine or N-acetylgalactosamine) while leaving the polypeptide intact. Chemical deglycosylation is described in Hakimuddin et al., 1987, Arch. Biochem. Biophys. 259:52 and in Edge et al., 1981, Anal. Biochem. 118:131. Enzymatic cleavage of carbohydrate residues on polypeptides can be achieved using a range of endo- and exoglycosidases, as described in Thotakura et al., 1987, Meth. Enzymol. 138:350. Glycosylation at potential glycosylation sites can be prevented using the compound tunicamycin as described in Duskin et al., 1982, J. Biol. Chem. 257:3105. Tunikamycin blocks the formation of protein-N-glycoside bonds.

Other modifications to the antibody design are also discussed in this document. For example, another type of covalent modification of an antibody construct includes linking the antibody construct to various non-protein polymers, including, but not limited to, various polyols such as polyethylene glycol, polypropylene glycol, polyoxyalkylenes, or copolymers of polyethylene glycol and polypropylene glycol, in the manner described in US Pat. Nos. 4,640,835; 4496689; 4301144; 4670417; 4,791,192 or 4,179,337. Also, as is known in the art, amino acid substitutions can be made at various positions within an antibody construct to facilitate the addition of polymers such as PEG.

In some embodiments, the covalent modification of antibody constructs of the invention includes the addition of one or more labels. The tag group can be coupled to the antibody construct via spacer legs of various lengths to reduce potential steric mismatch. Various methods of labeling proteins are known in the art and can be used to carry out the present invention. The term label or labeling group means any detectable label. In general, tags are divided into different classes depending on the method of detection - the following examples include, but are not limited to:

a) isotopic labels, which may be radioactive or heavy isotopes such as radioisotopes or radionuclides (e.g. ³ H, ¹⁴ C, ¹⁵ N, ³⁵ S, ⁸⁹ Zr, ⁹⁰ Y, ⁹⁹ Tc, ¹¹¹ In, ¹²⁵ 1, ¹³¹ I );

b) magnetic marks (eg magnetic particles);

c) redox active groups;

d) optical dyes (including, but not limited to, chromophores, luminophores, and fluorophores) such as fluorescent groups (e.g., FITC, rhodamine, lanthanide phosphorus), chemiluminescent groups, and fluorophores, which can be either low molecular weight fluorophores or protein fluorophores ;

e) enzymatic groups (eg horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase);

- 34 041992

f) biotinylated groups;

g) predefined polypeptide epitopes recognized by the secondary reporter (eg, leucine zipper pairing sequences, secondary antibody binding sites, metal binding domains, epitope tags, etc.).

The fluorescent label may be any molecule that can be detected due to its inherent fluorescent properties. Suitable fluorescent labels include, but are not limited to, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosin, coumarin, methylcoumarins, pyrene, malachite green, stilbene, lucifer yellow, cascade blue J, Texas red, IAEDANS, EDANS, BODIPY FL, LC Red 640, SU 5, SU 5.5, LC Red 705, Oregon Green, Alexa-Fluor dyes (Alexa Fluor 350, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660, Alexa Fluor 680), Cascade Blue, Cascade Yellow, and R-Phycoerythrin (PE) (Molecular Probs, Eugene, OR), FITC, Rhodamine, and Texas Red (Pierce, Rockford, IL), Cy5, Cy5.5, Su7 (Amersham Life Science, Pittsburgh, Pennsylvania). Suitable optical dyes, including fluorophores, are described in the Molecular Probes Handbook by Richard P. Haugland.

Suitable protein fluorescent labels also include, but are not limited to, green fluorescent protein, including GFP of Renilla, Ptilosarcus or Aequorea species (Chalfie et al., 1994, Science 263:802-805), EGFP (enhanced green fluorescent protein) (Clontech Laboratories , Inc., Genbank accession number U55762), blue fluorescent protein (BFP, Quantum Biotechnologies, Inc. 1801 de Maisonneuve Blvd. West, 8th Floor, Montreal, Quebec, Canada H3H 1J9; Stauber, 1998, Biotechniques 24:462-471; Heim et al., 1996, Curr. Biol. 6:178-182), enhanced yellow fluorescent protein (EYFP, Clontech Laboratories, Inc.), luciferase (Ichiki et al., 1993, J. Immunol. 150:5408-5417 ), β-galactosidase (Nolan et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:2603-2607) and Renilla (WO92/15673, WO95/07463, WO98/14605, WO98/26277, WO99/49019, U.S. Patent Nos. 5,292,658; 5,418,155; 5,683,888; 5,741,668;

Leucine zipper domains are peptides that promote oligomerization of the proteins in which they are found. Leucine zippers were originally identified in several DNA-binding proteins (Landschulz et al., 1988, Science 240:1759) and have since been found in a variety of different proteins. Among known leucine zippers are naturally occurring peptides and their derivatives that dimerize or trimerize. Examples of leucine zipper domains suitable for making soluble oligomeric proteins are described in PCT application WO 94/10308, and leucine zipper derived from lung surfactant protein D (SPD) is described in Knorre et al., 1994, FEBS Letters 344:191. The use of a modified leucine zipper that provides stable trimerization of the heterologous protein fused to it is described in Fanslow et al., 1994, Semin. Immunol. 6:267-78. In one approach, recombinant fusion proteins containing the anti-CD70 antibody fragment or derivatives fused to the leucine zipper peptide are expressed in suitable host cells, and the soluble anti-CD70 antibody oligomeric fragments or derivatives that form are isolated from the culture supernatant.

The antibody construct of the invention may also contain additional domains that are, for example, useful in isolating the molecule or relating to an adapted pharmacokinetic profile of the molecule. Domains useful for isolating an antibody construct can be selected from peptide motifs or re-introduced fragments that can be captured by an isolation technique such as an isolation column. Non-limiting embodiments of such additional domains include peptide motifs known as Myc-tag, HAT-tag, HA-tag, TAP-tag, GSTtag, chitin binding domain (CBD-tag), maltose-binding protein (MBP-tag), Flag-tag , Strep-tag and their variants (eg StrepII-tag) and His-tag. All antibody constructs described herein, characterized by identified CDRs, preferably contain a His-tag domain, which is commonly known as a repeat of consecutive His residues in the amino acid sequence of the molecule, preferably five, and more preferably six His residues (hexahistidine). The His-tag can be located, for example, at the N- or C-terminus of the antibody construct, preferably it is located at the C-terminus. Most preferably, a hexahistidine tag (HHHHH, see SEQ ID NO: 779) is peptide-linked to the C-terminus of the antibody construct of the invention.

The first binding domain of the antibody construct of the invention binds to human CD70 on the surface of the target cell. The preferred amino acid sequence of human CD70 is shown in SEQ ID NO: 741. It is understood that the term on the surface in the context of this invention means that the binding domain specifically binds to an epitope contained in the extracellular domain of CD70 (CD70 ECD). The first binding domain of the invention therefore preferentially binds to CD70 when it is expressed by naturally expressing cells or cell lines and/or cells or cell lines transformed or (stably/transiently) transfected with CD70. In a preferred embodiment, the first binding domain also binds to CD70 when CD70 is used as the mole

- 35 041992 target or ligand in an in vitro binding assay such as BIAcore or Scatchard. The target cell can be any prokaryotic or eukaryotic cell expressing CD70 on its surface; preferably, the target cell is a cell that is part of the human or animal body, such as a specific cancer cell selected, for example, from the group consisting of cancer of the kidney, lung, pancreas, ovary, breast, colon, or head and neck , melanoma, Kaposi's sarcoma, embryonic carcinoma, brain tumor, leukemia or lymphoma.

The term CD70 ECD refers to a form of CD70 that is substantially free of the transmembrane and cytoplasmic domains of CD70. One skilled in the art will appreciate that the transmembrane domain identified for the CD70 polypeptide of this invention is identified according to criteria commonly used in the art to identify this type of hydrophobic domain. The exact boundaries of the transmembrane domain may vary, but most likely by no more than 5 amino acids at either end of the domain specifically mentioned herein. The preferred human CD70 ECD is shown in SEQ ID NO: 742.

The affinity of the first binding domain for human CD70 is preferably <20 nM or <15 nM, more preferably <10 nM, even more preferably <5 nM, even more preferably <2 nM, even more preferably <1 nM, even more preferably <0. 6 nM, even more preferably <0.5 nM, and most preferably <0.4 nM. Affinity can be measured, for example, in the analysis of BIAcore or in the analysis of Scatchard, for example, as described in the examples. Other methods for determining affinity are also well known to those skilled in the art.

T cells or T lymphocytes are a type of lymphocyte (itself a type of white blood cell) that play a central role in cell-mediated immunity. There are several subsets of T cells, each with a specific function. T cells can be distinguished from other lymphocytes such as B cells and NK cells by the presence of a T cell receptor (TCR) on the cell surface. The TCR is responsible for the recognition of large histocompatible complex (MHC) antigens and is composed of two distinct protein chains. In 95% of T cells, the TCR consists of an alpha (α) and a beta (β) chain. When the TCR interacts with an antigenic peptide and an MHC (peptide/MHC complex), the T-lymphocyte is activated through a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptive molecules, and activated or released transcription factors.

The CD3 receptor complex is a protein complex and consists of four chains. In mammals, the complex contains a CD3y chain (gamma), a CD3δ chain (delta), and two CD3ε chains (epsilon). These chains bind to the T cell receptor (TCR) and the so-called ζ (zeta) chain to form the T cell CD3 receptor complex and generate an activation signal in T lymphocytes. The CD3y (gamma), CD3δ (delta) and CD3ε (epsilon) chains are tightly bound cell surface proteins of the immunoglobulin superfamily containing a single immunoglobulin extracellular domain. The intracellular tails of CD3 molecules contain one conserved motif, known as the immunoreceptor tyrosine-based activation motif, or short ITAM, which is required for TCR signaling. The CD3 epsilon molecule is a polypeptide that in humans is encoded by the CD3E gene located on chromosome 11. The most preferred CD3 epsilon epitope consists of amino acid residues 1-27 of the extracellular domain of human CD3 epsilon.

Redirected lysis of target cells by recruiting T cells with a multispecific, at least bispecific, antibody construct involves the formation of a cytolytic synapse and the delivery of perforin and granzymes. Engaged T cells are capable of serial lysis of target cells and are not affected by immune evacuation mechanisms that interfere with peptide antigen processing and presentation or clonal T cell differentiation; see, for example, WO 2007/042261.

Cytotoxicity mediated by CD70xCD3 bispecific antibody constructs can be measured in various ways. See examples 8.1-8.7. The effector cells can be, for example, stimulated enriched (human) CD8 positive T cells or unstimulated (human) peripheral blood mononuclear cells (PBMCs). If the target cells are of macaque origin, or macaque CD70 is expressed or transfected, the effector cells must also be of macaque origin, such as a macaque T cell line, eg 4119LnPx. Target cells must express (at least the extracellular domain of) CD70, eg human or macaque CD70. The target cells can be a cell line (such as CHO) that is stably or transiently transfected with CD70, eg human or macaque CD70. Alternatively, the target cells can be a cell line naturally expressing CD70, such as the human carcinoma OVCAR 8 cell line. Generally, EC50 values are expected to be lower with target cell lines expressing higher levels of CD70 on the cell surface. The ratio effector cell:target cell (E:T) is usually around 10:1, but can also vary. Cytotoxic activity of bispecific constructs

- 36 041992 CD70xCD3 antibodies can be measured in a 51-chromium release assay (incubation time about 18 hours) or in a FACS-based cytotoxicity assay (incubation time about 48 hours). Modifications to the assay incubation time (cytotoxic reaction) are also possible. Other methods for measuring cytotoxicity are well known to one of skill in the art and include MTT or MTC assays, ATP based assays including bioluminescent assays, sulpopodamine B (SRB) assay, WST assay, clonogenic assay, and ECIS technology.

Cytotoxic activity mediated by the CD70xCD3 bispecific antibody constructs of the invention is preferably measured in a cell-based cytotoxicity assay. It can also be measured in a 51-chromium release assay. It is represented by the EC ₅₀ value, which corresponds to half the maximum effective concentration (the concentration of the antibody construct that induces a cytotoxic response halfway between baseline and maximum). Preferably, the EC ₅₀ value of the CD70xCD3 bispecific antibody constructs is <10000 pM or <5000 pM, more preferably <4000 pM or <3000 pM, even more preferably <2000 pM or <1000 pM, even more preferably <500 pM or <400 pM, even more preferably <300 pM or <200 pM, even more preferably <100 pM or <50 pM, even more preferably <20 pM or <10 pM, and most preferably <5 pM or <2 pM or <1 pM, or even <0.5 pM or <0.2 pM or <0.1 pM.

The above EC ₅₀ values can be measured in various tests. One skilled in the art will recognize that the EC50 value is expected to be lower when stimulated/enriched CD8+ T cells are used as effector cells compared to unstimulated PBMC. In addition, EC50 values can be expected to be lower when the target cells express a high amount of the target antigen compared to a rat with low expression of the target antigen. For example, when stimulated/enriched human CD8+ T cells are used as effector cells (and transformed CD70 cells such as CHO cells or a CD70 cell line are used as target cells), the EC ₅₀ value of the CD70 xCD3 bispecific antibody construct is preferably < 1000 pM, more preferably <500 pM, even more preferably <250 pM, even more preferably <100 pM, even more preferably <50 pM, even more preferably <10 pM and most preferably <5 pM or <2 pM or <1 pM . When human PBMCs are used as effector cells, the EC ₅₀ value of the CD70xCD3 bispecific antibody construct is preferably <10000 pM or <5000 pM or <4000 pM (particularly when the target cells are a CD70 positive cell line), more preferably <2000 pM (particularly when the target cells are CD70 transfected cells such as CHO cells), more preferably <1000 pM or <500 pM, even more preferably <200 pM, even more preferably <150 pM, even more preferably <100 pM and most preferably <50 pM or <20 pM or less. When a macaque T cell line such as LnPx4119 is used as effector cells and a CD70 transfected macaque cell line such as CHO cells is used as target cell line, the EC ₅₀ value of the CD70xCD3 bispecific antibody construct is preferably <2000 μM or < 1500 pM, more preferably <1000 pM or <500 pM, even more preferably <300 pM or <250 pM, even more preferably <100 pM, and most preferably <50 or <20 pM, or less, such as <10, <5, <1 or <0.5 pM.

Preferably, the CD70xCD3 bispecific antibody constructs of the invention do not induce/mediate lysis or substantially induce/mediate lysis of CD70-negative cells such as CHO cells. The term does not induce lysis, does not substantially cause lysis, does not mediate lysis, or does not substantially mediate lysis, means that the antibody construct of the invention does not induce or mediate lysis by no more than 30%, preferably no more than 20%, more preferably not more than 10%, particularly preferably not more than 9%, 8%, 7%, 6% or 5% of negative CD70 cells, whereby the lysis of the CD70 cell line, (see below) is set to 100%. This is typically applied for antibody construct concentrations up to 500 nM. One skilled in the art knows how to measure cell lysis without additional steps. In addition, this document provides specific instructions for measuring cell lysis.

The difference in cytotoxic activity between the monomeric and dimeric isoform of individual anti-CD70xCD3 bispecific antibody constructs is referred to as the specific activity gap. This specific activity gap can, for example, be calculated as the ratio between the EC ₅₀ values of the monomeric and dimeric form of the molecule, see example 15. The specific activity gaps of the CD70xCD3 bispecific antibody constructs of this invention are preferably <5, more preferably <4, even more preferably < 3, even more preferably <2 or <1.5 and most preferably <1.

The first and/or second (or any other) binding domain(s) of an antibody construct of the invention is/are preferably cross-species, specific to the order mammal

- 37 041992 primates. Cross-species specific CD3 binding domains are, for example, described in WO 2008/119567. In one embodiment, the first and/or second binding domain, in addition to binding to human CD70 and human CD3, respectively, will also bind to CD70/CD3 of primates, including (but not limited to) New World primates (such as Callithrix jacchus, Saguinus Oedipus or Saimiri sciureus), Old World primates (such as baboons and macaques), gibbons, orangutans, and non-human hominids. It is contemplated that a first binding domain of an antibody construct of the invention that binds to human CD70 on the surface of a target cell also binds to at least macaque CD70 and/or a second binding domain that binds to human CD3 on the surface of a T cell also binds to at least with macaque CD3. A preferred macaque is Masaca fascicularis. Macaca mulatta (Rhesus) is also included.

A preferred bispecific antibody construct of the invention comprises a first binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell and at least macaque CD3.

In one aspect of the invention, the first binding domain binds to human CD70 and further binds to macaque CD70, such as Macaca fascicularis CD70, and more preferably macaque ECD CD70. Preferred Macaca fascicularis CD70 is shown in SEQ ID NO: 755. Preferred macaque CD70 ECD is shown in SEQ ID NO: 756. First binding domain affinity for macaque CD70 is preferably <50 nM or <40 nM, more preferably <30 nM or <20 nM , or <15 nM, more preferably <10 nM or <5 nM, even more preferably <2 nM or <1 nM, even more preferably <0.5 nM or <0.2 nM, and most preferably <0.1 nM .

Preferably, the affinity gap of the antibody constructs of the invention for binding macaque CD70 versus human CD70 [ma CD70:hu CD70] (as determined, for example, by the BiaCore or Scatchard method) is 0.1 to 10, more preferably 0.2 to 5 or 0.2 to 2, even more preferably 0.3 to 4, even more preferably 0.5 to 3 or 0.5 to 2.5 and most preferably 0.5 to 2 or 0.6 to 2. See examples 3 and 4.

In one embodiment of an antibody construct of the invention, the second binding domain binds to human CD3 epsilon and to Callithrix jacchus, Saguinus oedipus, or Saimiri sciureus CD3 epsilon. Preferably, the second binding domain binds to the extracellular epitope of these CD3 epsilon chains. The second binding domain is also expected to bind to an extracellular epitope of the CD3 epsilon chain of human and Macac. The most preferred CD3 epsilon epitope consists of amino acid residues 1-27 of the extracellular domain of human CD3 epsilon. More specifically, the epitope contains at least the amino acid sequence Gln-Asp-Gly-Asn-Glu.

Callithrix jacchus and Saguinus oedipus are New World primates belonging to the family Callitrichidae while Saimiri sciureus is a New World primate belonging to the family Cebidae.

It is particularly preferred for the antibody construct of the invention that the second binding domain that binds to human CD3 on the surface of the T cell contains a VL region containing CDR-L1, CDR-L2 and CDR-L3 selected from:

(a) CDR-L1 as shown in SEQ ID NO: 27 of WO 2008/119567, CDR-L2 as shown in SEQ ID NO: 28 of WO 2008/119567 and CDR-L3 as shown in SEQ ID NO: 29 of WO 2008/119567 ;

(b) CDR-L1 as shown in SEQ ID NO: 117 WO 2008/119567, CDR-L2 as shown in SEQ ID NO: 118 WO 2008/119567 and CDR-L3 as shown in SEQ ID NO: 119 WO 2008/119567 ; and (c) CDR-L1 as shown in SEQ ID NO: 153 WO 2008/119567, CDR-L2 as shown in SEQ ID NO: 154 WO 2008/119567 and CDR-L3 as shown in SEQ ID NO: 155 WO 2008/ 119567;

In an alternative preferred embodiment of the antibody design of this invention, the second binding domain that binds to human CD3 on the surface of the T cell contains a VH region containing CDR-H1, CDR-H2 and CDR-H3 selected from:

(a) CDR-H1 as shown in SEQ ID NO: 12 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 13 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 14 WO 2008/119567 ;

(b) CDR-H1 as shown in SEQ ID NO: 30 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 31 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 32 WO 2008/119567 ;

(c) CDR-H1 as shown in SEQ ID NO: 48 of WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 49 of WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 50 of WO 2008/119567 ;

(d) CDR-H1 as shown in SEQ ID NO: 66 of WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 67 of WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 68 of WO 2008/119567 ;

(e) CDR-H1 as shown in SEQ ID NO: 84 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 85 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 86 WO 2008/119567 ;

(f) CDR-H1 as shown in SEQ ID NO: 102 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 103 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 104 WO 2008/119567 ;

- 38 041992 (g) CDR-H1 as shown in SEQ ID NO: 120 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 121 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 122 WO 2008/119567;

(h) CDR-H1 as shown in SEQ ID NO: 138 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 139 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 140 WO 2008/119567 ;

(i) CDR-H1 as shown in SEQ ID NO: 156 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 157 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 158 WO 2008/119567 ; and (j) CDR-H1 as shown in SEQ ID NO: 174 WO 2008/119567, CDR-H2 as shown in SEQ ID NO: 175 WO 2008/119567 and CDR-H3 as shown in SEQ ID NO: 176 WO 2008/ 119567.

It is also preferred for the antibody construct of this invention that the second binding domain that binds to human CD3 on the surface of the T cell contains a VL region selected from the group consisting of the VL region shown in SEQ ID NOs: 35, 39, 125, 129, 161 or 165 of WO 2008/119567.

Alternatively, it is preferred that the second binding domain that binds to human CD3 on the surface of the T cell comprises a VH region selected from the group consisting of the VH region shown in SEQ ID NOs: 15, 19, 33, 37, 51, 55, 69, 73, 87, 91, 105, 109, 123, 127, 141, 145, 159, 163, 177 or 181 of WO 2008/119567.

More preferably, the antibody construct of the invention is characterized by a second binding domain that binds to human CD3 on the surface of a T cell, comprising a VL region and a VH region selected from the group consisting of:

(a) VL regions as shown in SEQ ID NO: 17 or 21 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 15 or 19 of WO 2008/119567;

(b) VL regions as shown in SEQ ID NO: 35 or 39 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 33 or 37 of WO 2008/119567;

(c) VL regions as shown in SEQ ID NO: 53 or 57 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 51 or 55 of WO 2008/119567;

(d) VL regions as shown in SEQ ID NO: 71 or 75 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 69 or 73 of WO 2008/119567;

(e) VL regions as shown in SEQ ID NO: 89 or 93 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 87 or 91 of WO 2008/119567;

(f) VL regions as shown in SEQ ID NO: 107 or 111 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 105 or 109 of WO 2008/119567;

(g) VL regions as shown in SEQ ID NO: 125 or 129 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 123 or 127 of WO 2008/119567;

(h) VL regions as shown in SEQ ID NO: 143 or 147 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 141 or 145 of WO 2008/119567;

(i) VL regions as shown in SEQ ID NO: 161 or 165 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 159 or 163 of WO 2008/119567;

(j) VL regions as shown in SEQ ID NO: 179 or 183 of WO 2008/119567 and VH regions as shown in SEQ ID NO: 177 or 181 of WO 2008/119567;

In a preferred embodiment of the antibody design of the invention, the binding domains, and in particular the second binding domain (which binds to human CD3 on the surface of a T cell), are in the following format: The pairs of VH regions and VL regions are in single chain antibody (scFv) format. The VH and VL regions are arranged in the order VH-VL or VL-VH. Preferably, the VH region is positioned N-terminally to the linker sequence and the VL region is positioned from the C-terminus of the linker sequence.

A preferred embodiment of the antibody construct of the invention described above is characterized by a second binding domain that binds to human CD3 on the surface of a T cell, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 23, 25, 41, 43, 59, 61, 77, 79, 95, 97, 113, 115, 131, 133, 149, 151, 167, 169, 185 or 187 of WO 2008/119567.

Therefore, in one embodiment, an antibody construct of the invention comprises a polypeptide selected from the group consisting of those shown in SEQ ID NO: 10, SEQ ID NO: 20, SEQ ID NO: 30, SEQ ID NO: 40, SEQ ID NO: 50, SEQ ID NO: 60, SEQ ID NO: 70, SEQ ID NO: 80,

SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO

90, SEQ ID NO: 100, SEQ ID NO: 110, SEQ ID NO: 120, SEQ ID NO: 130, SEQ ID NO: 140,

150 SEQ ID NO

210, SEQ ID NO

270 SEQ ID NO

330 SEQ ID NO

390 SEQ ID NO

450 SEQ ID NO

510 SEQID NO

570 SEQ ID NO

160 SEQ ID NO

220 SEQ ID NO

280 SEQ ID NO

340 SEQ ID NO

400 SEQID NO

460, SEQ ID NO

520 SEQ ID NO

580 SEQ ID NO

170 SEQ ID NO

230, SEQ ID NO

290 SEQ ID NO

350 SEQ ID NO

410 SEQ ID NO

470 SEQ ID NO

530 SEQ ID NO

590 SEQ ID NO

180 SEQ ID NO

240 SEQ ID NO

300 SEQID NO

360 SEQID NO

420 SEQ ID NO

480 SEQ ID NO

540 SEQ ID NO

600 SEQID NO

190, SEQ ID NO

250 SEQ ID NO

310 SEQ ID NO

370 SEQ ID NO

430, SEQ ID NO

490 SEQ ID NO

550 SEQ ID NO

610 SEQ ID NO

200, 260, 320, 380,

440, 500, 560, 620,

- 39 041992

SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO

630, SEQ ID NO: 640, SEQ ID NO: 650, SEQ ID NO: 660, SEQ ID NO: 670, SEQ ID NO: 680,

690, SEQ ID NO: 700, SEQ ID NO: 710, SEQ ID NO: 720, SEQ ID NO: 730, SEQ ID NO: 740,

923, SEQ ID NO: 927, SEQ ID NO: 931, SEQ ID NO: 935, SEQ ID NO: 939, SEQ ID NO: 943,

947, SEQ ID NO: 951, SEQ ID NO: 955, SEQ ID NO: 959, SEQ ID NO: 963, SEQ ID NO: 967,

971, SEQ ID NO: 975, SEQ ID NO: 979, SEQ ID NO: 983, SEQ ID NO: 987, SEQ ID NO: 991,

995, SEQ ID NO: 999, SEQ ID NO: 1003, SEQ ID NO: 1007, SEQ ID NO: 1011, SEQ ID NO:

1015, SEQ ID NO: 1019, SEQ ID NO: 1023, SEQ ID NO: 1027, SEQ ID NO: 1031, SEQ ID NO: 1035, SEQ ID NO: 1039, SEQ ID NO: 1043, SEQ ID NO: 1053, SEQ ID NO: 1057, SEQ ID NO: 1067, SEQ ID NO: 1071, SEQ ID NO: 1081, SEQ ID NO: 1085, SEQ ID NO: 1095, SEQ ID NO: 1099, SEQ ID NO: 1109, SEQ ID NO: 1113, SEQ ID NO: 1123, SEQ ID NO: 1127, SEQ ID NO: 1137, SEQ ID NO: 1141, SEQ ID NO: 1151, SEQ ID NO: 1155, SEQ ID NO: 1165, SEQ ID NO: 1169, SEQ ID NO: 1179, SEQ ID NO: 1183, SEQ ID NO: 1193, SEQ ID NO: 1197, SEQ ID NO: 1207, SEQ ID NO: 1211, SEQ ID NO: 1221, SEQ ID NO: 1225, SEQ ID NO: 1235, SEQ ID NO: 1239, SEQ ID NO: 1249, SEQ ID NO: 1253, SEQ ID NO: 1263, SEQ ID NO: 1267, SEQ ID NO: 1277, SEQ ID NO: 1281, SEQ ID NO: 1291, SEQ ID NO: 1295, SEQ ID NO: 1305, SEQ ID NO: 1309, SEQ ID NO: 1319, SEQ ID NO: 1323, SEQ ID NO: 1333, SEQ ID NO: 1337, SEQ ID NO: 1347, SEQ ID NO: 1351, SEQ ID NO: 1361, SEQ ID NO: 1365, SEQ ID NO: 1375, SEQ ID NO: 1379, SEQ ID NO: 1389, SEQ ID NO: 1393, SEQ ID NO: 1403, SEQ ID N O: 1407, SEQ ID NO: 1417, SEQ ID NO: 1421, SEQ ID NO: 1431, SEQ ID NO: 1435, SEQ ID NO: 1445, SEQ ID NO: 1449, SEQ ID NO: 1459, SEQ ID NO: 1463, SEQ ID NO: 1473, SEQ ID NO: 1477, SEQ ID NO: 1487, SEQ ID NO: 1491, SEQ ID NO: 1501, SEQ ID NO: 1505, SEQ ID NO: 1515, SEQ ID NO: 1519, SEQ ID NO: 1529, SEQ ID NO: 1533, SEQ ID NO: 1543, SEQ ID NO: 1547, SEQ ID NO: 1557, SEQ ID NO: 1561, SEQ ID NO: 1571 and SEQ ID NO: 1575.

It is preferred if the antibody construct of the invention contains a polypeptide selected from the group consisting of the polypeptides shown in SEQ ID NO: 1053, SEQ ID NO: 1095, SEQ ID NO: 1151, SEQ ID NO: 1179, SEQ ID NO: 1193 , SEQ ID NO: 1221, SEQ ID NO: 1235, SEQ ID NO: 1249, SEQ ID NO: 1263, SEQ ID NO: 1277, SEQ ID NO: 1347, SEQ ID NO: 1361, SEQ ID NO: 1375, SEQ ID NO: 1431 and SEQ ID NO: 1445.

Modifications to the amino acid sequences of the antibody constructs described herein are also contemplated. For example, it may be desirable to improve the affinity and/or other biological properties of an antibody construct. Amino acid sequence variants of antibody constructs are obtained by making appropriate nucleotide modifications to the nucleotide sequence encoding the antibody construct, or by peptide synthesis. All amino acid sequence modifications described below should result in an antibody construct that still retains the desired biological activity (binding to CD70 and CD3) of the unmodified parent molecule.

The term amino acid or amino acid residue generally refers to an amino acid having a definition recognized in the art, such as an amino acid selected from the group consisting of: alanine (Ala or A); arginine (Arg or R); asparagine (Asn or N); aspartic acid (Asp or D); cysteine (Cys or C); glutamine (Gln or Q); glutamic acid (Glu or E); glycine (Gly or G); histidine (His or H); isoleucine (He or I): leucine (Leu or L); lysine (Lys or K); methionine (Met or M); phenylalanine (Phe or F); proline (Pro or P); serine (Ser or S); threonine (Thr or T); tryptophan (Trp or W); tyrosine (Tyr or Y) and valine (Val or V), although modified, synthetic or rare amino acids may be used. Generally, amino acids can be grouped as having a non-polar side chain (eg, Ala, Cys, He, Leu, Met, Phe, Pro, Val); a negatively charged side chain (eg Asp, Glu); a positively charged side chain (eg Arg, His, Lys); or an uncharged polar side chain (eg Asn, Cys, Gln, Gly, His, Met, Phe, Ser, Thr, Trp and Tyr).

Amino acid modifications include, for example, deletions and/or insertions and/or substitutions of residues in the amino acid sequences of an antibody construct. Any combination of deletions, insertions, and substitutions can be made to produce the final construct, as long as the final construct has the desired characteristics. Amino acid substitutions can alter the post-translational processes of antibody construction, such as changing the number or position of glycosylation sites.

For example, 1, 2, 3, 4, 5, or 6 amino acids can be inserted or deleted in each of the CDRs (depending on their length, of course), while 1, 2, 3, 4, 5, 6, 7, 8 , 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 25 amino acids may be inserted or deleted in each of the FRs. Preferably, amino acid sequence insertions include N- and/or C-terminal fusions ranging from 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 residues to polypeptides containing one hundred or more residues, as well as inserts one or more amino acid residues within a sequence. An insertion variant of an antibody construct of the invention comprises a fusion to the N-terminus or C-terminus of an enzyme antibody construct, or a fusion to a polypeptide that increases the serum half-life of the antibody construct.

Sites of greatest interest for displacement mutagenesis include heavy and/or light chain CDRs, in particular hypervariable regions, but FR rearrangements in

- 40 041992 light and/or heavy chains are also considered. The substitutions are preferably conservative substitutions as described herein. Preferably, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids may be substituted in the CDR, while 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 25 amino acids may be substituted in the framework regions (FRs), depending on the length of the CDR or FR. For example, if a CDR sequence contains 6 amino acids, one, two, or three of those amino acids are assumed to be substituted. Similarly, if the CDR sequence contains 15 amino acids, one, two, three, four, five, or six of these amino acids are assumed to be substituted.

A useful method for identifying certain residues or regions of antibody constructs that are preferred sites for mutagenesis is called alanine scanning mutagenesis, as described by Cunningham and Wells in Science, 244: 1081-1085. This method identifies a residue or group of target residues within the boundaries of an antibody construct ( for example, charged residues such as arg, asp, his, lys and glu) and replace them with neutral or negatively charged amino acids (most preferably alanine or polyalanine) to achieve an interaction of amino acids with the epitope.

Such amino acid positions that are functionally sensitive to substitutions are further modified by introducing additional or other variants at the substitution sites. Thus, while the site or site of introduction of amino acid sequence variants is predetermined, the nature of the mutation per se may not necessarily be predetermined. For example, to analyze or optimize the occurrence of a mutation at a given site, alanine-scanning or selective mutagenesis can be performed at the target codon and target region and expressed antibody variants are screened for the optimal combination of a given activity. Methods for introducing substitution mutations at predetermined sites in DNA having a known sequence are well known, such as M13 primer mutagenesis and PCR mutagenesis. Mutants are screened by antigen binding activity assays, such as CD70 or CD3 binding assays.

In general, if amino acids are substituted in one or more or all of the heavy and/or light chain CDRs, it is preferred that the substituted sequence then obtained is at least 60% or 65%, more preferably 70% or 75%, even more preferably 80% or 85%, particularly preferably 90% or 95% identical to the original CDR sequence. This means that it depends on the length of the CDR to what extent it is identical to the substituted sequence. For example, a CDR containing 5 amino acids is preferably 80% identical to its substituted sequence in order to have at least one substituted amino acid. Accordingly, the CDRs of an antibody construct may have varying degrees of identity with their substituted sequences, for example, CDRL1 may have 80% while CDRL3 may have 90%.

Preferred substitutions (or substitutions) are conservative substitutions. However, any substitution (including non-conservative substitution or one or more of the illustrative substitutions shown in Table 3 below) is contemplated as long as the antibody construct retains its ability to bind to CD70 via the first binding domain and to CD3 or CD3 epsilon via the second binding domain. and/or its CDRs have at least 60% or 65% identity with the subsequently substituted sequence, more preferably 70% or 75%, even more preferably 80% or 85%, particularly preferably 90% or 95% identity with the original CDR sequence.

Conservative substitutions are listed in Table 3 under the heading preferred substitutions. If such substitutions alter biological activity, they are the most significant changes and are listed in Table 3 under the heading generic substitutions, or as further described below with respect to amino acid classes, may be introduced and products screened.

Table 3

Amino acid substitutions

Initial Typical substitutions Preferred substitutions Ala (A) val, leu, ile val Arg(R) lys, gin, asn lys Asn(N) gin, his, asp, lys, gin

- 41 041992

arg Asp(D) glu, asn glu Cys(C) ser, ala ser Gin (Q) asn, glu asn Glu(E) asp, gin asp Gly (G) Ala ala His(H) asn, gin, lys, arg arg He(I) leu, val, met, ala, phe leu Leu(L) norleucine, ile, val, met, ala ile Lys (K) arg, gin, asn arg Met(M) leu, phe, ile leu Phe(F) leu, val, ile, ala, tyr tyr Pro (P) Ala ala Ser(S) Thr thr Thr(T) Ser ser TRP(W) tyr, phe tyr Tyr (Y) trp, phe, thr, ser phe Val(V) ile, leu, met, phe, ala leu

Significant modifications to the biological properties of the antibody constructs of this invention are accompanied by selective substitutions that differ significantly in their ability to maintain (a) the structure of the polypeptide backbone in the region of substitution, for example, a folded or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, and (c ) side chain dimensions. Residues of natural origin are divided into groups depending on the general properties of the side chains: (1) hydrophobic: norleucine, met, ala, val, leu, ile; (2) neutral hydrophilic: cys, ser, thr; (3) acidic: asp, glu; (4) basic: asn, gin, his, lys, arg; (5) residues that affect chain orientation: gly, pro; and (6) aromatic: trp, tyr, phe.

Non-conservative substitutions lead to the replacement of a representative of one of these classes by a representative of another class. Cysteine residues that are not involved in maintaining the proper conformation of the antibody construct can also be replaced primarily with serine to enhance the oxidative stability of the molecule and prevent unwanted crosslinking. Conversely, cysteine bonds can be introduced into an antibody molecule to improve its stability (especially when the antibody is an antibody fragment, such as an Fv fragment).

In the case of amino acid sequences, sequence identity and/or similarity is determined using standard methods known in the art, including, but not limited to, the Local Sequence Identity Algorithm by Smith and Waterman, 1981, Adv. Appl. Math. 2:482, sequence identity alignment algorithm Needleman and Wunsch, 1970, J. Mol. Biol. 48:443, similarity search method Pearson and Lipman, 1988, Proc. Nat. Acad. sci. U.S.A. 85:2444, computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics software package, Genetics Computer Group, 575 Science Dr., Madison, WI), Best Fit sequence program described by Devereux et al., 1984, Nucl. Acid Res. 12:387-395, preferably used with the default parameters or fitting method. Preferably, percent identity is calculated by FastDB based on the following parameters: mismatch penalty 1; penalty for gap 1; gap size penalty 0.33; and compound penalty 30, Current Methods in Sequence Comparison and Analysis, Macromolecule Sequencing and Synthesis, Selected Methods and Applications, pp 127-149 (1988), Alan R. Liss, Inc.

An example of an algorithm used is PILEUP. PILEUP creates a multiple sequence alignment from a group of related sequences using a progressive, pairwise alignment. It is also possible to build a tree showing the group relationships used to create the alignment. PILEUP uses a simplification of the progressive leveling method Feng & Doolittle, 1987, J. Mol. Evol. 35:351-360; the method is similar to that described in Higgins and Sharp, 1989, CABIOS 5:151-153. Applied PILEUP parameters include a default gap weight of 300, a default gap length weight of 0.10, and weighted end gaps.

Another example of a useful algorithm is the BLAST algorithm described in: Altschul et al., 1990, J. Mol. Biol. 215:403-410; Altschul et al., 1997, Nucleic Acids Res. 25:3389-3402 and Karin et al., 1993, Proc. Natl. Acad. sci. U.S.A. 90:5873-5787. A particularly suitable BLAST program is

- 42 041992 ma WU-BLAST-2, which was obtained from Altschul et al., 1996, Methods in Enzymology 266:460-480. WU-BLAST-2 uses several search parameters, most of which have default values set. Adjustable parameters are set with the following values for proteins: overlap length=1, percentage of overlap=0.125, threshold segment length, T=P. Parameters HSP S and HSP S2 are dynamic values and are set by the program itself depending on the composition of a particular sequence and the composition of a particular database against which the sequence of interest is searched; however, these values can be corrected to increase the sensitivity.

An additional algorithm used is gapped BLAST, which is described in Altschul et al., 1993, Nucl. Acids Res. 25:3389-3402. Gap BLAST uses the BLOSUM-62 substitution weighting matrix; the threshold parameter T is set to 9; two-match method for triggering extensions without gaps, cost per gap length to cost 10+k; Xu is set to 16 and Xg is set to 40 in the database search step and 67 in the output step of the algorithms. Gap alignment is triggered at an estimate corresponding to approximately 22 bits.

In general, the amino acid homology, similarity, or identity between individual variant CDRs is at least 60% relative to the sequences illustrated herein, and generally with preferably increasing homology or identity of at least 65% or 70, more preferably at least 75% or 80%, most preferably at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and substantially 100%. Likewise, percent (%) nucleotide sequence identity relative to the nucleotide sequence of the binding proteins identified herein is presented as the percentage of nucleotide residues in a candidate sequence that are identical to nucleotide residues in an antibody coding sequence. The specific method uses a WU-BLAST-2 BLASTN module with default parameters, with overlap length and overlap ratio set to 1 and 0.125, respectively.

In general, the nucleotide homology, similarity, or identity between the nucleotide sequences encoding individual variant CDRs and the nucleotide sequences depicted herein is at least 60% or more typically, with preferred increasing homologies or identities being at least 65, 70 , 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% and almost 100%. Thus, a CDR variant is one with specified homology, similarity, or identity to the parent CDR of the invention and shares a biological function, including but not limited to at least 60, 65, 70, 75, 80, 81, 82, 83 , 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% specificity and/or activity of the parental CDR.

In one embodiment of the invention, the percent identity of antibody constructs of the invention to human germline is >70 or >75%, more preferably >80 or >85%, even more preferably >90%, and most preferably >91, >92, >93, >94, >95 or even >96, >97 or >98%. See Example 7. Identity with human germline antibody gene products is believed to be an important feature to reduce the risk of using therapeutic proteins to induce an immune response against a drug in a patient during treatment. Hwang and Foote (Immunogenicity of engineered antibodies; Methods 36 (2005) 3-10) demonstrated that reducing the number of non-human portions of antibody drug constructs resulted in a reduced risk of inducing anti-drug antibodies in patients during treatment. Comparing an exhaustive number of clinically assessed antibodies with corresponding immunogenicity data, it is shown that humanization of antibody V regions renders the protein less immunogenic (average 5.1% of patients) than antibodies bearing unaltered non-human V regions (average 23.59 % of patients). Therefore, a higher degree of identity with human sequences is desirable for V-region based protein therapy in the form of antibody constructs. For this purpose of determining germline identity, VL V regions can be aligned with the amino acid sequences of human germline V and J segments (http://vbase.mrc-cpe.cam.ac.uk/) using Vector NTI software. and amino acid sequence calculated by dividing identical amino acid residues by the total number of VL amino acid residues in percent. The same can be done for VH segments (http://vbase.mrc-cpe.cam.ac.uk/) except that VH CDR3 may be excluded due to its great diversity and lack of existing VH CDR3 alignment patterns human germ line. Recombinant techniques can then be used to increase the sequence identity of human germline genes.

In another embodiment, the bispecific antibody constructs of the invention exhibit high monomer yields under standard study scale conditions, eg, in a standard two-step purification process. Preferably the monomer yield of the antibody constructs of the invention is >0.25 mg/l supernatant, more preferably

- 43 041992 >0.5 mg/l, even more preferably >1 mg/l and most preferably >2.5 mg/l of the supernatant.

Similarly, the yield of isoforms of dimeric antibody constructs, and hence the percentage of monomers of antibody constructs, can be determined (ie, monomer: (monomer+dimer)). The performance of the monomeric and dimeric antibody constructs and the calculated percentage of monomer can, for example, be obtained from the purification step of the SEC obtained from the culture supernatant from a standardized spinning flask manufacturing process. In one embodiment, the percentage of antibody construct monomers is >80%, more preferably >85%, even more preferably >90%, and most preferably >95%.

In one embodiment, the antibody construct has a preferred plasma stability (ratio of EC50 with plasma to EC50 without plasma) <8 or <7 or <6, more preferably <5 or <4, more preferably <3.5 or <3, still more preferably <2.5 or <2, and most preferably <1.5 or <1. Plasma stability of an antibody construct can be tested by incubating the construct in human plasma at 37° C. for 24 hours, followed by EC50 determination in a 51-chromium release cytotoxicity assay. Effector cells in the cytotoxicity assay can stimulate enriched human CD8-positive T cells. Target cells can, for example, be CHO cells transfected with human CD70. The target cell effector ratio (E:T) can be selected as 10:1. The pool of human plasma used for this purpose is derived from the blood of healthy donors collected with EDTA-coated syringes. Cellular components are removed by centrifugation, and the upper phase of the plasma is collected and then combined. As a construct control, antibodies are diluted immediately prior to cytotoxicity assay in RPMI-1640 medium. Plasma stability is calculated as the ratio of EC50 (after plasma incubation) to EC50 (control). See example 11.

It is also preferred that the monomer-dimer conversion of the antibody constructs of the invention be low. The conversion can be measured under various conditions and analyzed using high performance size exclusion chromatography. See example 9. For example, incubation of monomeric isoforms of antibody constructs can be carried out for 7 days at 37°C and a concentration of, for example, 100 μg/ml or 250 μg/ml in an incubator. Under these conditions, it is preferred that the antibody constructs of the invention exhibit a dimer percentage of <5%, more preferably <4%, even more preferably <3%, even more preferably <2.5%, still more preferably <2%, still more preferably <1.5% and most preferably <1, <0.6, or <0.5, <0.3, or even 0%.

It is also preferred that the bispecific antibody constructs of this invention have very low dimeric conversion after a number of freeze/thaw cycles. For example, a monomeric antibody construct is brought to a concentration of 250 µg/ml, for example, in the original preparation buffer and subjected to three freeze/thaw cycles (freeze at -80°C for 30 min followed by thawing for 30 min at room temperature ) followed by high throughput SEC to determine the percentage of the originally monomeric antibody construct that has been converted to a dimeric antibody construct. Preferably, the dimeric percentages of the bispecific antibody constructs are <5%, more preferably <4%, even more preferably <3%, even more preferably <2.5%, even more preferably <2%, even more preferably <1.5%, and most preferably <1% or even <0.5% or 0%, for example after three freeze/thaw cycles.

The bispecific antibody constructs of this invention preferably exhibit favorable thermal stability with aggregation temperatures >45 or >50°C, more preferably >52 or >54°C, even more preferably >56 or >57°C, and most preferably >58 or >59 °С, or >60°С. The thermal stability parameter can be determined in terms of antibody aggregation temperature as follows: An antibody solution at a concentration of 250 μg/ml is transferred into a disposable cuvette and placed in a dynamic light scattering (DLS) device. The sample is heated from 40 to 70° C. at a heating rate of 0.5° C./min, continuously obtaining a measured radius. To calculate the aggregation temperature of an antibody, an increase in radius indicating protein melting and aggregation is used. See example 10.

Alternatively, temperature melt curves can be determined using differential scanning calorimetry (DSC) to determine the intrinsic biophysical stability of antibody construct proteins. These experiments are performed using a VP-DSC MicroCal LLC device (Northampton, Massachusetts, USA). The energy capture of the sample containing the antibody construct is recorded from 20 to 90°C compared to the sample containing only drug buffer. The antibody constructs are adjusted to a final concentration of 250 μg/ml, eg in SEC buffer. To record an appropriate melting curve, the total temperature of the sample is increased in steps. At each temperature T, the energy absorption of the sample and the buffer solution of the drug is recorded. The difference in energy absorption Cp (kcal/mol/°C) of the sample minus the reference value is plotted against the corresponding temperature. Temperature

- 44 041992 melting point is defined as the temperature at the first energy absorption maximum.

In addition, it is contemplated that the CD70xCD3 bispecific antibody constructs of the invention are not cross-specific with (ie, do not substantially bind to) the human CD70 paralog CD40L. Furthermore, it is contemplated that the CD70xCD3 bispecific antibody constructs of the invention are not cross-specific with (ie, do not substantially bind to) the CD40L macaque/cynomolgus CD70 paralog. See example 6.

In addition, binding of the first binding domain of antibody constructs of the invention to human CD70 is expected to be reduced by <25%, preferably <20%, more preferably <15%, more preferably <10%, even more by the presence of soluble CD27. preferably <5% and most preferably <2%. It is assumed that the concentration of CD27 in this context is physiological, for example, between about 100 and about 500 pg/ml or even higher, for example, up to 1 μg/ml. See example 16 for more details on the analysis.

The CD70xCD3 bispecific antibody constructs of the invention also provide for a turbidity (measured by OD340 after adjusting the concentration of purified monomeric antibody to 2.5 mg/mL and overnight incubation) of <0.2, preferably <0.15, more preferably <0.12, even more preferably <0.1 and most preferably <0.08 or <0.05. See example 12.

It is contemplated that the CD70xCD3 bispecific antibody constructs of the invention should not be internalized, or should not be significantly internalized by the target cell. Changes in specific activity of a CD70xCD3 bispecific antibody construct can be measured as a function of pre-incubation of the construct on target cells in the absence of T cells. If the antibody construct is internalized, it must undergo lysosomal degradation. The effective concentration should decrease with time, and therefore the apparent efficiency should also decrease. The effect is observed with other targets for which this phenomenon is known.

The percentage of internalization can be analyzed, for example, as follows: T cells are counted and diluted to a concentration of 1x105 ml in assay medium. CD70 positive (eg, natural expressing) cells are counted and plated at 2500 cells per well (cpw). The antibody construct is diluted serially 1:2 at an initial concentration of 100 nM. The antibody construct is added to culture plates at 0, 1 or 2 h incubation prior to the addition of T cells. The T cells are then seeded at 25,000 cpw and the test sample is incubated for 48 hours at 37°C. The target cell survival assay is performed, for example, on the Steady-Glo® system (25 μl/well). Preferably, the percentage of internalization is <20% after 2 hours (pre)incubation of the antibody construct with the target cell, more preferably <15%, even more preferably <10% and most preferably <5%.

In yet another embodiment of the invention, the antibody construct of the invention is stable at acidic pH. The more tolerant the antibody construct behaves at a non-physiological pH, such as pH 5.5 (the pH required to run, for example, cation exchange chromatography), the greater the recovery of the antibody construct eluted from the ion exchange column relative to the total amount of protein loaded. Recovery of antibody construct from an ionic (eg, cationic) exchange column at pH 5.5 is preferably >50%, more preferably >60% or >65%, more preferably >70% or >72% or >74% or > 76%, or >78%, even more preferably >80%, even more preferably >90%, even more preferably >95% and most preferably >99%. See example 13.

In addition, the bispecific antibody constructs of this invention are expected to exhibit therapeutic efficacy or antitumor activity. This can, for example, be evaluated in a study as described in the following example of an advanced human tumor xenograft model:

On day 1 of the study, 5x106 human CD70-positive human cancer cell lines were subcutaneously injected into the right flank of female NOD/SCID mice. When the average tumor volume reached about 100 mm ³ , in vitro expanded human CD3-positive T cells were transplanted into mice by injecting about 2x10 ⁷ cells into the abdominal cavity of the animals. Placebo control group 1 mice did not receive effector cells and were used as non-transplant controls for comparison with placebo control group 2 (received effector cells) to monitor the effect of T cells alone on tumor growth. Antibody treatment was started when the average tumor volume reached about 200 mm ³ . The mean tumor size of each treatment group on the day of treatment initiation should not be statistically different from any other group (analysis of variance). Mice were treated with 0.5 mg/kg/day of the CD70xCD3 bispecific antibody construct by intravenous bolus injection for about 15-20 days. Tumors were measured with calipers during the study, and the results were evaluated by intergroup comparison of tumor volumes (TV). Tumor growth inhibition T/C [%] was determined by calculating TV as T/C %=100 x (median TV of the analyzed group)/(median TV of the control group 2).

- 45 041992

One of skill in the art knows how to modify or tailor certain parameters of this assay, such as the number of tumor cells injected, site of injection, number of transplanted human T cells, number of bispecific antibody constructs to be administered, and timing, while still achieving meaningful and reproducible result. Preferably, the tumor growth inhibition T/C [%] is <70 or <60, more preferably <50 or <40, even more preferably <30 or <20, and most preferably <10 or <5 or even <2.5.

The invention also provides a polynucleotide/nucleic acid molecule encoding an antibody construct of the invention.

A polynucleotide is a biopolymer consisting of 13 or more nucleotide monomers covalently linked in a chain. DNA (such as cDNA) and RNA (such as mRNA) are examples of polynucleotides with a distinct biological function. Nucleotides are organic molecules that serve as monomers or subunits of nucleic acid molecules such as DNA or RNA. The nucleic acid molecule or polynucleotide can be double-stranded and single-stranded, linear and cyclic. It is preferably contained in a vector, which is preferably contained in the host cell. Said host cell, for example, after transformation or transfection with the vector or polynucleotide of the invention, is capable of expressing the antibody construct. For this purpose, the polynucleotide or nucleic acid molecule is operably linked to control sequences.

The genetic code is a set of rules by which information encoded in genetic material (nucleic acids) is translated into proteins. Biological decoding in living cells is carried out by the ribosome, which links the amino acids in the order determined by the mRNA, using tRNA molecules to carry the amino acids and read three nucleotides of the mRNA at a time. The code specifies how the sequences of these nucleotide triplets, called codons, determine which amino acid will be added next during protein synthesis. With few exceptions, a three-nucleotide codon in a nucleic acid sequence specifies one amino acid. Since the vast majority of genes are encoded with exactly the same code, this particular code is often referred to as the canonical or standard genetic code. While the genetic code determines the protein sequence for a given coding region, other genomic regions can influence when and where these proteins are produced.

In addition, the present invention provides a vector containing the polynucleotide/nucleic acid molecule of the invention.

A vector is a nucleic acid molecule used as a carrier to transfer (foreign) genetic material into a cell. The term vector includes, but is not limited to, plasmids, viruses, cosmids, and artificial chromosomes. In general, the constructed vectors contain an origin of replication, a multiple cloning site, and a selectable marker. The vector itself is typically a nucleotide sequence, usually a DNA sequence, that contains an insert (transgene) and a larger sequence that serves as the backbone of the vector. Modern vectors may contain additional features besides the transgene insert and scaffold: a promoter, a genetic marker, antibiotic resistance, a reporter gene, a targeting sequence, a protein purification tag. Vectors, referred to as expression vectors (expression constructs), are specifically designed to express a transgene in a target cell and typically have control sequences.

The term control sequences refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. Control sequences that are suitable for prokaryotes include, for example, a promoter, an optional operator sequence, and a ribosome binding site. Promoters, polyadenylation signals, and enhancers are known to be used in eukaryotic cells.

A nucleic acid is operably linked when it is placed in a functional dependency of another nucleic acid sequence. For example, a presequence or secretory leader DNA is operably linked to a polypeptide's DNA if it is expressed as a precursor protein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is located in such a way as to facilitate translation. In general, operably linked means that the DNA sequences, when linked, are contiguous and, in the case of a secretory leader, contiguous and in the reading phase. However, enhancers do not have to be contiguous. The bond is formed by ligation at suitable restriction sites. If such sites are not present, synthetic oligonucleotide adapters or linkers are used, in accordance with common practice.

Transfection is the process of intentionally introducing nucleic acid molecules

- 46 041992 slots or polynucleotides (including vectors) into target cells. This term is mainly used for non-viral methods in eukaryotic cells. Transduction is often used to describe the virus-mediated transfer of nucleic acid molecules or polynucleotides. Transfection of animal cells typically involves opening transient pores or holes in the cell membrane to allow uptake of the material. Transfection can be carried out using calcium phosphate, by electroporation, by squeezing cells, or by mixing a cationic lipid with material to produce liposomes that fuse with the cell membrane and deposit their contents inside.

The term transformation is used to describe the non-viral transfer of nucleic acid molecules or polynucleotides (including vectors) into bacteria as well as non-animal eukaryotic cells, including plant cells. Thus, transformation is a genetic change in a bacterial or non-animal eukaryotic cell resulting from direct uptake through the cell membrane(s) from its environment and subsequent incorporation of exogenous genetic material (nucleic acid molecules). Transformation can be done by artificial means. To transform, cells or bacteria must be in a state of competence, which can manifest as a time-limited response to environmental conditions such as depletion and cell density.

In addition, the present invention provides a host cell transformed or transfected with a polynucleotide/nucleic acid molecule or a vector of the invention.

As used herein, the terms host cell or recipient cell are intended to include any individual cell or cell culture that can be or is a recipient of vectors, exogenous nucleic acid molecules, and polynucleotides encoding an antibody construct of the invention; and/or recipients of the antibody construct itself.

The introduction of the appropriate material into the cell is carried out by transformation, transfection and the like. The term host cell is also intended to include progeny or potential progeny of a single cell. Since certain changes may occur in subsequent generations due to natural, accidental or intentional mutation, or due to environmental influences, such progeny may not actually be completely identical (in morphology or genomic or complete DNA complement) to the parent cell, but all still included within the scope of the term used in this document. Suitable host cells include prokaryotic or eukaryotic cells, and include, but are not limited to, bacteria, yeast cells, fungal cells, plant cells, and animal cells such as insect cells and mammalian cells, such as mouse, rat, macaque, or human cells.

The antibody construct of the invention can be produced in bacteria. After expression, the antibody construct of the invention is isolated from the E. coli cell paste in the soluble fraction and can be purified by, for example, affinity chromatography and/or size exclusion. The final purification can be performed in a manner analogous to the purification of an antibody expressed, for example, in CHO cells.

In addition to prokaryotes, eukaryotic microorganisms such as filamentous fungi or yeasts are suitable hosts for cloning or expression of antibody constructs of the invention. Saccharomyces cerevisiae, or baker's yeast, is the most widely used host microorganism among lower eukaryotes. However, a number of other genera, species and strains are generally available and available herein, such as Schizosaccharomyces pombe, Kluyveromyces hosts such as K. lactis, K. fragilis (ATCC 12424), K. bulgaricus (ATCC 16045), K. wickeramii (ATCC 24178), K. waltii (ATCC 56500), K. drosophilarum (ATCC 36906), K. thermotolerans, and K. marxianus; yarrowia (EP 402226); Pichia pastoris (EP 183070); Candida Trichoderma reesia (EP 244234); Neurospora crassa; species of the genus Schwanniomyces such as Schwanniomyces occidentalis and filamentous fungi such as Neurospora, Penicillium, Tolypocladium, and hosts of the genus Aspergillus such as A. nidulans and A. niger.

Suitable host cells for expression of the glycosylated antibody construct of the invention are derived from multicellular organisms. Examples of invertebrate cells include plant and insect cells. Numerous strains and variants of baculoviruses and corresponding host cells of susceptible insects such as Spodoptera frugiperda (Foliar armyworm), Aedes aegypti (Yellow fever mosquito), Aedes albopictus (Asian tiger mosquito), Drosophila melanogaster (Drosophila fruit fly), and Bombyx mori have been identified. (Silkworm). A number of viral strains are available for transfection, for example Autographa californica NPV variant L-1 and Bombyx mori NPV strain Bm-5; such viruses can be used as the virus of the present invention, in particular for transfection of Spodoptera frugiperda cells.

Cell cultures of cotton, corn, potato, soybean, petunia, tomato, Arabidopsis and tobacco plants can also be used as hosts. Those skilled in the art are aware of cloning and expression vectors useful in the production of proteins in plant cell culture. See, for example, Hiatt et al., Nature (1989) 342: 76-78, Owen et al. (1992) Bio/Technology 10: 790-794, Artsaenko et

- 47 041992 al. (1995) The Plant J 8: 745-750, and Fecker et al. (1996) Plant Mol Biol 32: 979-986.

However, the greatest interest is shown in relation to vertebrate cells, and the propagation of vertebrate cells in culture (tissue culture) has become a daily procedure. Examples of suitable mammalian cell lines are CV1 monkey kidney cell line transformed with SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture as described in Graham et al., J. Gen Virol. 36:59 (1977)); newborn hamster kidney cells (BHK, ATCC CCL 10); Chinese hamster ovary cells/-DHFR (CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77: 4216 (1980)); mouse Sertoli cells (TM4, Mather, Biol. Reprod. 23: 243-251 (1980)); monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL1587); human cervical carcinoma cells (HELA, ATCC CCL 2); dog kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, 14138065); mouse mammary tumor cells (MMT 60562, ATCC CCL51); TRI cells (Mather et al., Annals N. Y Acad. Sci. (1982) 383: 44-68); MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2).

In yet another embodiment, the invention relates to a method for producing an antibody construct of the invention, said method comprising culturing a host cell of the invention under conditions to express the antibody constructs of the invention and recovering the produced antibody construct from the culture.

As used herein, the term culture refers to the maintenance, differentiation, growth, proliferation and/or expansion of cells in vitro under suitable media conditions. The term expression includes any step involved in the production of an antibody construct of the invention, including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion.

When using recombinant techniques, the antibody construct can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. When using recombinant techniques, the antibody construct can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. Carter et al., Bio/Technology 10: 163-167 (1992) describes a procedure for isolating antibodies secreted into the periplasmic space of E. coli. Briefly, the cell mass is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonyl chloride (PMSF) for approximately 30 minutes. Residual cells can be removed by centrifugation. If the antibody is secreted into the medium, the supernatant from such expression systems is typically first concentrated using commercially available protein concentration filters, such as Amicon or Millipore Pellicon ultrafiltration units. A protease inhibitor such as PMSF may be included to inhibit proteolysis in any of the previous steps, and antibiotics may be added to prevent the growth of incidental contaminants.

An antibody construct of the invention derived from host cells can be isolated or purified using, for example, hydroxyapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography. In addition, depending on the antibody to be purified, other protein purification techniques are available, e.g., ion exchange column fractionation, ethanol precipitation, reverse phase HPLC, heparin-SEPHAROSE™ chromatography, anion or cation exchange resin chromatography (e.g., on a column with polyaspartic acid), chromatofocusing, electrophoresis in SDS-PAGE and precipitation with ammonium sulfate. When an antibody construct of the invention contains a CH3 domain, Bakerbond ABX resin (J.T. Baker, Philipsburg, NJ) is useful for purification.

The preferred purification technique is affinity chromatography. The matrix to which the affinity ligand is attached is most often agarose, but other matrices are also available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow higher flow rates and shorter processing times than with agarose.

In addition, the present invention provides a pharmaceutical composition comprising an antibody construct of the invention or an antibody construct produced in accordance with the method of the invention.

As used herein, the term pharmaceutical composition refers to a composition that is suitable for administration to a patient, preferably a human. A particularly preferred pharmaceutical composition of the invention comprises one or more antibody construct(s) of the invention, preferably in a therapeutically effective amount. Preferably, the pharmaceutical composition further comprises suitable compositions of one or more (pharmaceutically effective) carriers, stabilizers, excipients, diluents, solubilizers, surfactants, emulsifiers, preservatives and/or adjuvants. Acceptable constituents of the composition are preferably non-toxic to recipients at the dosages and concentrations used. Pharmaceutical compositions of the invention include, but are not limited to, liquid, frozen, and lyophilized compositions.

- 48 041992

Compositions of the invention may contain a pharmaceutically acceptable carrier. In general, as used herein, the term pharmaceutically acceptable carrier means any and all aqueous and non-aqueous solutions, sterile solutions, diluents, buffers such as phosphate buffered saline (PBS), water, suspensions, emulsions such as oil/water emulsions, various types of wetting agents, liposomes, dispersion media and coatings that are compatible with pharmaceutical administration, in particular parenteral administration. The use of such media and agents in pharmaceutical compositions is well known in the art, and compositions containing such carriers can be formulated using known conventional methods.

In some embodiments, the invention provides pharmaceutical compositions comprising an antibody construct of the invention, and additionally one or more excipients, such as those described in this section and elsewhere in this document. Excipients may be used in this invention in this regard for a wide variety of purposes such as controlling the physical, chemical or biological properties of compositions such as controlling viscosity and/or methods of the invention to improve the performance and/or stabilize such formulations and processes against degradation and deterioration associated, for example, with stresses arising during manufacture, transport, storage, pre-cooking, introduction and after that.

In certain embodiments, a pharmaceutical composition may contain formulation materials to modify, maintain, or maintain, for example, pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, absorption, or permeation of the composition (see REMINGTON'S PHARMACEUTICAL SCIENCES, 18 Edition, (A.R. Genrmo, ed.), 1990, Mack Publishing Company). In such embodiments, suitable formulation materials may include, but are not limited to:

amino acids such as glycine, alanine, glutamine, asparagine, threonine, proline, 2-phenylalanine, including charged amino acids, preferably lysine, lysine acetate, arginine, glutamate and/or histidine antimicrobial agents such as antibacterial and antifungal agents antioxidants such as ascorbic acid, methionine, sodium sulfite or sodium hydrosulfite;

buffers, buffer systems, and buffer agents that are used to maintain the composition at physiological pH or at a slightly lower pH, typically in the pH range of about 5 to about 8 or 9; examples of buffers are borate, bicarbonate, tris-HCl, citrates, phosphates or other organic acids, succinate, phosphate, histidine and acetate; for example Tris buffer, pH about 7.0-8.5, or acetate buffer, pH about 4.0-5.5;

non-aqueous solvents such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate;

aqueous vehicles, including water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffer media;

biodegradable polymers such as polyesters;

bulking agents such as mannitol or glycine;

chelating agents such as ethylenediaminetetraacetic acid (EDTA);

isotonic and absorbent delaying agents;

complexing agents such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin) fillers;

monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose, or dextrins); carbohydrates may be non-reducing sugars, preferably trehalose, sucrose, octasulfate, sorbitol or xylitol;

(low molecular weight) proteins, polypeptides or protein carriers such as human or bovine serum albumin, gelatin or immunoglobulins, preferably of human origin;

dyes and flavors;

sulfur-containing reducing agents such as glutathione, thioctic acid, sodium thioglycolate, thioglycerol, [alpha]-monothioglycerol and sodium thiosulfate diluents;

emulsifiers;

hydrophilic polymers such as polyvinylpyrrolidone;

salt-forming counterions such as sodium;

preservatives such as antimicrobials, antioxidants, chelating agents, inert gases, and the like;

examples are: benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide);

metal complexes such as Zn-protein complexes;

solvents and co-solvents (such as glycerin, propylene glycol or polyethylene glycol);

sugars and sugar alcohols such as trehalose, sucrose, octasulfate, mannitol, sorbitol or xylitol,

- 49 041992 staniose, mannose, sorbose, xylose, ribose, myonisitose, galactose, lactitol, ribitol, myonisitol, galactitol, glycerol, cyclitols (eg inositol) glycol; and polyols of sugars;

suspending agents;

surfactants or wetting agents such as pluronics, PEGs, sorbitan esters, polysorbates such as polysorbate 20, polysorbate, triton, tromethamine, lecithin, cholesterol, tyloxapal; surfactants can be detergents, preferably >1.2 kDa molecular weight and/or polyester, preferably >3 kDa molecular weight; non-limiting examples of preferred detergents are Tween 20, Tween 40, Tween 60, Tween 80 and Tween 85; non-limiting examples for preferred polyesters are PEG 3000, PEG 3350, PEG 4000 and PEG 5000;

stability improving agents such as sucrose or sorbitol;

tonicity enhancing agents such as alkali metal halides, preferably sodium or potassium chloride, mannitol, sorbitol;

parenteral delivery vehicles, including sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's solutions, or fixed oils;

intravenous excipients, including solutions for replenishing fluid or nutrient deficiencies, electrolyte solutions (for example, solutions based on Ringer's dextrose).

It will be appreciated by those skilled in the art that different constituents of a pharmaceutical composition (eg, those listed above) may have different effects, for example, an amino acid may act as a buffer, stabilizer, and/or antioxidant; mannitol can act as a bulking agent and/or tonicity agent; sodium chloride can act as a delivery vehicle and/or tonicity agent; and so on.

It is contemplated that the composition of the invention may contain, in addition to the polypeptide of the invention as defined herein, additional biologically active agents, depending on the intended use of the composition. Such agents may be drugs that act on the gastrointestinal system, drugs that act as cytostatic agents, drugs that prevent hyperuricemia;

drugs that inhibit immunoreactive reactions (eg, corticosteroids), drugs that modulate the inflammatory response, drugs that act on the circulatory system, and/or agents such as cytokines known in the art. It is also contemplated that the antibody construct of this invention is used in co-therapy, ie in combination with another anti-cancer drug.

In certain embodiments of the invention, the optimal pharmaceutical composition is determined by a person skilled in the art depending on, for example, the route of administration, the delivery format, and the required dosage. See, for example, REMINGTON'S PHARMACEUTICAL SCIENCES, supra. In certain embodiments of the invention, such compositions can affect the physical state, stability, in vivo release rate, and in vivo clearance rate of the antibody constructs of the invention. In certain embodiments of the invention, the main medium or carrier in the pharmaceutical composition may be aqueous or non-aqueous in nature. For example, a suitable stock solution or carrier may be water for injection, physiological saline, or artificial cerebrospinal fluid, optionally supplemented with other materials common in parenteral formulations. Neutral buffered saline or saline mixed with serum albumin are additional exemplary media. In certain embodiments, compositions containing antibody constructs of the invention can be prepared for storage by mixing the selected composition, having the required degree of purity, with optional agents (REMINGTON'S PHARMACEUTICAL SCIENCES, see above) in the form of a lyophilized tablet or aqueous solution. Additionally, in certain embodiments of the invention, the antibody construct of the invention can be obtained as a lyophilisate using appropriate excipients, such as sucrose.

If parenteral administration is envisaged, therapeutic compositions for use in the present invention may be in the form of a pyrogen-free, parenterally acceptable aqueous solution containing the desired antibody construct of the invention in a pharmaceutically acceptable carrier medium. A particularly suitable stock solution for parenteral injection is sterile distilled water to which an antibody construct of the invention has been added as a sterile, isotonic solution with an appropriate preservative. In certain embodiments of the invention, the preparation may include mixing the desired molecule with an agent, such as injectable microspheres, biodegradable particles, polymeric compounds (such as polylactic acid or polyglycolic acid), granules or liposomes, which can provide controlled or prolonged release of the product, which can be delivered via depot injection. In certain embodiments of the invention, it is also possible to use

- 50 041992 hyaluronic acid, which helps to prolong the circulation period. In certain embodiments, implantable drug delivery devices may be used to introduce the desired antibody construct.

The existence of additional pharmaceutical compositions is obvious to those skilled in the art, including sustained or controlled delivery/release dosage forms of the antibody construct of the invention. Methods for preparing various other sustained or controlled delivery agents, such as liposomal vehicles, biodegradable microparticles or porous granules, and depot injections, are also known to those skilled in the art. See, for example, International Patent Application No. PCT/US93/00829 which describes the controlled release of porous polymeric microparticles for the delivery of pharmaceutical compositions. Sustained release formulations may include semi-permeable polymeric matrices in the form of molded articles such as films or microcapsules. Extended release matrices may include polyesters, hydrogels, polylactides (as described in US Pat. No. 3,773,919 and European Patent Application Publication No. EP 058481), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman et al., 1983, Biopolymers 2: 547-556), poly(2hydroxyethyl methacrylate) (Langer et al., 1981, J. Biomed. Mater. Res. 15:167-277 and Langer, 1982, Chem. Tech. 12:98-105), ethylene vinyl acetate (Langer et al., 1981, supra) or poly-O(-)-3-hydroxybutyric acid (EP Published Application No. EP 133988). Sustained release formulations may also include liposomes, which can be prepared by any of several methods known in the art. See, for example, Eppstein et al., 1985, Proc. Natl. Acad. sci. U.S.A. 82:3688-3692; European Patent Application Publication No. EP 036676; EP 088046 and EP 143949.

The antibody constructs can be incorporated into microcapsules prepared, for example, by coacervation or interfacial polymerization techniques (e.g., hydroxymethylcellulose or gelatin and poly(methyl methacrylate) microcapsules, respectively), into colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsion. Such techniques are disclosed in Remington's Pharmaceutical Sciences 16th edition, Oslo, A., Ed., (1980).

Pharmaceutical compositions used for in vivo administration are generally provided as sterile preparations. Sterilization can be accomplished by filtration through sterile filtration membranes. If the composition is lyophilized, sterilization by this method can be carried out both before and after lyophilization and reconstitution. Compositions for parenteral administration may be stored in lyophilized form or in solution. Parenteral compositions are generally placed in a container with a sterile inlet, for example, an intravenous solution bag or vial with a stopper pierced by a hypodermic injection needle.

Another aspect of the invention includes a self-buffered antibody construct of the invention which can be used as pharmaceutical compositions as described in International Patent Application WO 06138181A2 (PCT/US2006/022599). A variety of exposures are available for protein stabilization and materials and preparation methods useful in this regard, such as Arakawa et al., Solvent interactions in pharmaceutical formulations, Pharm Res. 8(3): 285-91 (1991); Kendrick et al., Physical stabilization of proteins in aqueous solution in: RATIONAL DESIGN OF STABLE PROTEIN FORMULATIONS: THEORY AND PRACTICE, Carpenter and Manning, eds. Pharmaceutical Biotechnology. 13:61-84 (2002), and Randolph et al., Surfactant-protein interactions, Pharm Biotechnol. 13: 159-75 (2002), see especially the components and methods for their preparation for self-buffered protein compositions in accordance with the present invention, especially protein pharmaceutical products and processes for veterinary and/or medical purposes.

Salts can be used in accordance with some embodiments of the invention, for example, to adjust the ionic strength and/or isotonicity of the composition and/or to improve the solubility and/or physical stability of the protein or other ingredient of the composition in accordance with the invention. As is known, ions can stabilize the natural state of proteins by binding to charged residues on the surface of the protein and by screening charged and polar groups in the protein and reducing the strength of their electrostatic interactions, attractive and repulsive interactions. The ions can also stabilize the denatured state of the protein by binding, in particular, to the denatured peptide bonds (-CONH) of the protein. In addition, ionic interaction with charged and polar groups in a protein can also reduce intermolecular electrostatic interactions and thereby prevent or reduce protein aggregation and insolubility.

Ionic species vary considerably in their effect on proteins. A number of categorical rankings of ions and their effect on proteins have been developed that can be used in the development of pharmaceutical compositions in accordance with the invention. One example is the Hofmeister series, which ranks ionic and polar non-ionic solutions, influencing the conformational stability of proteins in solution. Stabilizing solutes are called cosmotropic

- 51 041992 mi. Destabilizing solutes are called chaotropic. Cosmotropes are typically used at high concentrations (eg > 1 mol ammonium sulfate) to precipitate proteins from solution (salting out). Chaotropes are commonly used to reduce and/or solubilize proteins (salting). The relative effectiveness of ions in salting out and salinity determines their position in the Hofmeister series.

Free amino acids can be used in the construction of antibodies according to the invention in accordance with various embodiments of the invention as excipients, stabilizers and antioxidants, as well as other standard applications. To stabilize the proteins in the preparation, lysine, proline, serine and alanine can be used. Glycine is used during lyophilization to ensure the correct structure and properties of the tablet. Arginine can be used to inhibit protein aggregation in both liquid and lyophilized formulations. Methionine is used as an antioxidant.

Polyols include sugars such as mannitol, sucrose and sorbitol, polyhydric alcohols such as, for example, glycerol and propylene glycol, and, for the purposes of this invention, polyethylene glycol (PEG) and related substances. The polyols are cosmotropic. They are used as stabilizing agents in both liquid and lyophilized formulations to protect proteins from physical and chemical degradation processes. Polyols are also used to adjust the tonicity of drugs. Among the polyols useful in certain embodiments of the invention is mannitol, commonly used to provide structural stability to the precipitate in lyophilized formulations. It ensures the stability of the structure to precipitation. It is generally used in conjunction with a lyoprotectant such as sucrose. Sorbitol and sucrose are among the preferred tonicity adjusting agents and as stabilizers to protect against freeze-thaw stress during shipping or bulk preparation during the manufacturing process. Reducing sugars (containing free aldehyde or ketone groups), such as glucose and lactose, can glycate surface lysines and arginine residues. Therefore, they are generally not among the preferred polyols for use in accordance with the invention. In addition, sugars which form reactive species such as sucrose, which hydrolyze to fructose and glucose under acidic conditions and hence cause glycation, are also not among the preferred polyols of the invention in this respect. PEG is used to stabilize proteins and as a cryoprotectant, and in this regard it can be used in this invention.

Embodiments of the antibody construct of the invention also include surfactants. Protein molecules can be subject to adsorption on surfaces and denaturation and subsequent aggregation at air-liquid, solid-liquid and liquid-liquid interfaces. These effects are generally inversely proportional to protein concentration. These deleterious interactions are generally inversely related to protein concentration and are typically exacerbated by physical shaking such as occurs during product handling and shipping. Surfactants are typically used to prevent, minimize, or reduce such surface adsorption. Suitable surfactants in the invention in this regard include polysorbate 20, polysorbate 80, other fatty acid esters of sorbitan polyethoxylates, and poloxamer 188. Also, surfactants have traditionally been used to regulate the conformational stability of proteins. The use of surfactants in this regard is specific to the protein, since any given surfactant will generally stabilize some proteins and destabilize others.

Polysorbates are susceptible to oxidative degradation and are often said to contain sufficient peroxides to cause oxidation of protein side chains, especially methionine. Therefore, polysorbates should be used with caution and, when used, should be used at their lowest effective concentration. In this regard, polysorbates represent the general rule that excipients should be used at their lowest effective concentrations.

Embodiments of the antibody construct of the invention further include one or more antioxidants. To some extent, harmful protein oxidation can be prevented in pharmaceutical compositions by maintaining proper ambient oxygen levels and temperatures and avoiding exposure to light. Antioxidants can also be used to prevent oxidative degradation of proteins. Suitable antioxidants in this respect include reducing agents, oxygen/free radical scavengers and chelating agents.

Antioxidants for use in therapeutic protein compositions according to the invention are preferably water soluble and retain their activity throughout the shelf life of the product. EDTA is the preferred antioxidant according to the invention in this respect. Antioxidants can damage proteins. For example, reducing agents such as glutathione in particular can disrupt intramolecular disulfide bonds. Thus, the antioxidants for use in the invention are selected, inter alia, for

- 52 041992 reducing or sufficiently reducing the likelihood that they themselves will damage the proteins in the composition.

The preparations according to the invention may contain metal ions which are protein coexductors and which are necessary for the formation of protein coordination complexes, such as zinc, which is necessary for the formation of certain insulin suspensions. Metal ions can also inhibit some of the processes in which protein degradation occurs. However, metal ions also catalyze physical and chemical processes that degrade proteins. Magnesium ions (10120 mm) can be used to suppress the isomerization of aspartic acid to isoaspartic acid. Ca ⁺² ions (up to 100 mM) can increase the stability of human deoxyribonuclease. Mg ⁺² , Mn ⁺² and Zn ⁺² , however, can destabilize human deoxyribonuclease (rhDNase). By analogy, Ca ⁺² and Sr ⁺² can stabilize factor VIII, it can be destabilized with Mg ⁺² , Mn ⁺² and Zn ⁺² , Cu ⁺² and Fe ⁺² ions, and its aggregation can be increased with Al ⁺³ .

Embodiments of the antibody construct of the invention further include one or more preservatives. Preservatives are needed in the development of multi-dose parenteral products for which more than one set from the same container is provided. Their main function is to inhibit the growth of microorganisms and guarantee the sterility of the product during the expiration date or term of use of the medicinal product. Traditionally used preservatives include benzyl alcohol, phenol and m-cresol. Although preservatives have a long history of use with small molecule parenterals, the development of protein formulations containing preservatives can be challenging. Preservatives almost always have a destabilizing effect (aggregation) on proteins, and this has become a major factor limiting their use in multi-dose protein formulations. To date, most protein formulations have been developed for single use only. However, when multi-dose formulations are possible, they have the added benefit of providing patient convenience and increased competitiveness. A good example is human growth hormone (hGH), where the development of conserved formulations has led to the commercialization of more convenient, reusable pen-format injection devices. There are currently at least four such pen-sized devices available on the market containing stored hGH formulations. Norditropin (Liquid, Novo Nordisk), Nutropin AQ (Liquid, Genentech) & Genotropin (lyophilized dual chamber cartridge, Pharmacia & Upjohn) contain phenol, while Somatrope (Eli Lilly) is formulated with m-cresol. When developing and creating canned dosage forms, several aspects must be considered. The effective concentration of the preservative in the drug product must be optimized. This calls for testing this preservative in dosage form with concentration ranges that confer antimicrobial efficacy without compromising protein stability.

As would be expected, the development of liquid formulations containing preservatives is more complex than lyophilized formulations. Freeze-dried products may be freeze-dried without a preservative and reconstituted with a diluent-containing preservative at the time of use. This reduces the time the preservative is in contact with the protein, greatly minimizing the associated stability risks. When using liquid formulations, preservative effectiveness and stability must be maintained throughout the shelf life of the product (18 to 24 months). It is important to note that the effectiveness of the preservative must be demonstrated in the final formulation containing the active drug and all excipient components.

The antibody constructs described herein can also be formulated as immunoliposomes. A liposome is a small vesicle composed of various types of lipids, phospholipids and/or surfactants that are suitable for drug delivery to a mammal. The components of a liposome are typically organized in a bilayer composition, similar to the distribution of lipids in biological membranes. Liposomes containing antibody constructs are prepared using methods known in the art, such as those described in Epstein et al., Proc. Natl. Acad. sci. USA 82: 3688 (1985); Hwang et al., Proc. Natl Acad. sci. USA 77: 4030 (1980); US patent. Nos. 4485045 and 4544545; and WO 97/38731. Liposomes with extended circulation time are described in US Pat. No. 5,013,556. Particularly suitable liposomes can be prepared using a reverse phase evaporation process using a lipid composition containing phosphatidylcholine, cholesterol and phosphatidylethanolamine derivatives with PEG (PEG-PE). Liposomes are extruded through filters with a defined pore size to obtain liposomes having a target diameter. Fab' fragments of an antibody construct of the invention can be conjugated to liposomes as described in Martin et al. J Biol. Chem. 257: 286-288 (1982) via a disulfide exchange reaction. The chemotherapeutic agent is optionally contained within a liposome. See Gabizon et al. J. National Cancer Inst. 81 (19) 1484 (1989).

Once prepared, the pharmaceutical composition may be stored in a sterile vial as a solution, suspension, gel, emulsion, solid, crystal, or dehydrated lyophilized powder. Such preparations can be stored both in ready-to-use form and in a form (eg, lyophilized) that is reconstituted prior to administration.

The biological activity of a pharmaceutical composition as defined herein can be determined, for example, by a cytotoxicity assay as described in the following examples, in WO 99/54440 or in Schlereth et al. (Cancer Immunol. Immunother. 20 (2005), 1-12). Efficacy or in vivo efficacy as used herein refers to response to therapy with a pharmaceutical composition of the invention, using, for example, standardized NCI response criteria. The efficacy or in vivo efficacy of a therapy using a pharmaceutical composition of the invention refers to the efficacy of the composition for its intended purpose, i.e. the ability of the composition to produce its desired effect, i.e. the depletion of pathological cells, eg tumor cells. In vivo efficacy can be monitored by established standard methods for appropriate disease subjects including, but not limited to, white blood cell count, differentials, fluorescent activated cell sorting, bone marrow aspiration. In addition, various clinical disease chemistry parameters and other established standard methods may be used. In addition, computed tomography, x-ray, nuclear magnetic resonance imaging (eg, to evaluate results based on the National Cancer Institute [Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, GrilloLopez A , Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP Report of an international workshop to standardize response criteria for nonHodgkin's lymphomas NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr; 17(4):1244]), positron emission tomography, leukocyte count, differentials, fluorescently activated cell sorting, bone marrow aspiration, lymph node biopsy/histology, and various clinical chemistry parameters of lymphoma (eg, lactate dehydrogenase) and other established standard methods.

Another important goal in drug development, such as the pharmaceutical composition of the invention, is the predictable modulation of pharmacokinetic properties. To this end, it is possible to establish a pharmacokinetic profile of a drug candidate, that is, a profile of pharmacokinetic parameters that affect the ability of a particular drug to treat a given condition.

Pharmacokinetic parameters of a drug that affect the ability of a drug to treat a particular disease include, but are not limited to: half-life, volume of distribution, first-pass metabolism, and serum binding. Each of the above parameters can affect the effectiveness of this drug.

Half-life refers to the time at which 50% of an administered drug is eliminated by biological processes such as metabolism, excretion, etc. By first-pass hepatic metabolism is meant the propensity of a drug to be metabolized upon first contact with the liver, i.e. during its first passage through the liver. Volume of distribution refers to the degree of retention of a drug in all compartments of the body, eg, intracellular and extracellular spaces, tissues and organs, etc., and the distribution of the drug in these compartments. The degree of binding in blood serum means the propensity of the drug to interact with blood serum proteins and their binding to blood serum proteins, such as albumin, resulting in a decrease or loss of the biological activity of the drug.

Pharmacokinetic parameters also include bioavailability, delay time (Tlag), Tmax, rate of absorption, greater appearance and/or Cmax for a given amount of drug administered. Bioavailability refers to the amount of drug in the blood compartment. Lag time means the time delay between administration of a drug and its detection and measurability in blood or plasma. Tmax is the time after which the maximum blood concentration of the drug is reached, and Cmax is the maximum blood concentration obtained with the drug. The time to reach the concentration of the drug in the blood or tissue, which is required for its biological effect, depends on all parameters. Pharmacokinetic parameters of bispecific antibody constructs exhibiting cross-species specificity, which can be determined in preclinical animal studies in non-chimpanzee primates as described above, are also set forth, for example, in Schlereth et al. (Cancer Immunol. Immunother. 20 (2005), 1-12).

In one embodiment, the invention provides an antibody construct of the invention, or an antibody construct prepared according to the method of the invention, for use in the prevention, treatment, or amelioration of a tumor or cancer, or metastatic cancer. It is assumed that this tumor, cancer or metastatic cancer is CD70-expressing.

The formulations described herein are useful as pharmaceutical compositions for the treatment, amelioration and/or prevention of a medical condition as described herein in a patient in need thereof. The term treatment refers to both therapeutic intervention and prophylactic or preventive measures. Treatment includes

- 54 041992 use or administration of a drug into an organism, isolated tissue or cell in a patient who has a disease/disorder, a symptom of a disease/disorder or a predisposition to a disease/disorder with the aim of curing, treating, partially relieving symptoms, alleviating, modifying, eliminating, improve, alleviate or influence a disease, a symptom of a disease, or a predisposition to a disease.

As used herein, the term amelioration refers to any improvement in the disease state of a patient having a tumor or cancer, or metastatic cancer as defined herein below, by administering an antibody construct of the invention to a subject in need thereof. Such an improvement can also be considered as slowing or stopping the progression of cancer or metastatic cancer in a patient. As used herein, the term prophylaxis means preventing the occurrence or reappearance of a patient having a tumor or cancer or metastatic cancer as defined herein below by administering an antibody construct according to the invention to a subject in need thereof.

The term disease refers to any condition that could be corrected by treatment with an antibody construct or a pharmaceutical composition as described herein. This term encompasses chronic and acute disorders or diseases, including those pathological conditions that increase the susceptibility of a mammal to the disease in question.

A neoplasm is an abnormal growth of tissue, usually but not always forming a mass. When a mass also forms, it is usually referred to as a tumor. Neoplasms or tumors can be benign, potentially malignant (precancerous), or malignant.

Malignant neoplasms are commonly referred to as cancer. They usually invade and destroy surrounding tissue and may form metastases, i.e. they spread to other parts, tissues, or organs of the body. Therefore, the term metastatic cancer covers metastases to other tissues or organs, as opposed to the original tumor. Lymphomas and leukemias are lymphoid neoplasms. For the purposes of this invention, they are also covered by the terms tumor or cancer.

In a preferred embodiment, the tumor or cancer is selected from the group consisting of kidney, lung, pancreas, ovary, breast, colon, head and neck, stomach, rectum, thymus, brain, leukemia, lymphoma, melanoma , Kaposi's sarcoma, embryonic carcinoma, and metastatic cancer arising from any of the above.

More specifically, the tumor or cancer may be selected from the group consisting of renal cell carcinoma (RCC), clear cell RCC (ccRCC), papillary RCC, chromophobe RCC, sarcomatoid RCC, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma, pancreatic adenocarcinoma gland, such as ductal adenocarcinoma of the pancreas, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma, carcinoma of the larynx, carcinoma of the pharynx, carcinoma of the nasopharynx, undifferentiated carcinoma of the nasal part of the nasopharynx, lymphoepithelioma, glioblastoma, glioma, meningioma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), T-cell leukemia, adult T-cell leukemia, B-cell cancer, B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL) ), multiple myeloma, cutaneous T-cell lymphoma, nodular small cell with cleavage core lymphoma, lymphocytic lymphoma, peripheral T-cell lymphoma, Lennert's lymphoma, immunoblastic lymphoma, T-cell lymphoma, entroblastic/centrocytic (cb/cc) follicular lymphoma, angioimmunoblastic lymphadenopathic (AILD)-like HIV-associated T-cell lymphoma body cavity lymphomas, Castleman's disease, or Waldenström's macroglobulinemia. Metastatic cancer may be a derivative of any of the above.

The invention also provides a method for treating or improving a cancer or metastatic cancer, comprising the step of administering to a subject in need thereof an antibody construct of the invention or an antibody construct prepared according to the method of the invention. It is assumed that this tumor, cancer or metastatic cancer is CD70-expressing.

The terms subject in need or in need of treatment include those who already have the disorder as well as those in whom the disorder is to be prevented. A subject in need or diseased includes humans and other mammalian subjects who are receiving either prophylactic or therapeutic treatment.

An antibody design in accordance with the present invention is generally designed for specific routes and routes of administration, for specific dosages and frequencies of administration, for specific treatment of specific diseases, with ranges of bioavailability and persistence, among others. The materials of the composition are preferably formulated in concentrations suitable for the site of administration.

Thus, preparations and compositions can be designed in accordance with the invention.

- 55 041992 niem for delivery by any suitable route of administration. In the context of this invention, routes of administration include, but are not limited to:

topical application (such as dermal, inhalation, nasal, ophthalmic, auricular/auditory, vaginal, mucosal);

enteral routes (such as oral, gastrointestinal, sublingual, sublabial, buccal, rectal); and parenteral routes (such as intravenous, intraarterial, intraosseous, intramuscular, intracerebral, intracranial, epidural, spinal, subcutaneous, intraperitoneal, extraamniotic, intraarticular, intracardiac, intradermal, intralesional, intrauterine, intravesical, intravitreal, transdermal, intranasal, transmucosal, intrasynovial, intraluminal).

Pharmaceutical compositions and antibody constructs of this invention are particularly useful for parenteral administration, such as subcutaneous or intravenous delivery, for example, by injection, such as a bolus injection, or by infusion, such as continuous infusion. Pharmaceutical compositions can be administered using a medical device. Examples of medical devices for the administration of pharmaceutical compositions are described in US Pat. Nos. 4,475,196; 4439196; 4447224; 4447233; 4486194; 4487603; 4596556; 4790824; 4941880; 5064413; 5312335; 5312335; 5383851 and 5399163.

In particular, the present invention provides for the continuous administration of a suitable composition. As a non-limiting example, continuous or substantially continuous, ie continuous, administration can be accomplished with a small pump system carried by the patient to measure the influx of the therapeutic agent into the patient's body.

A pharmaceutical composition containing an antibody construct of the invention may be administered using said pumping systems. Such pumping systems are generally known in the art and typically rely on periodic replacement of cartridges containing the therapeutic agent to be administered. When replacing a cartridge in such a pumping system, a temporary interruption of the otherwise uninterrupted flow of the therapeutic agent to the patient may occur. In such a case, the administration phase before the cartridge change and the administration phase after the cartridge change will still be considered in the sense of the pharmaceutical agents and methods of the invention together constitute one continuous administration of such a therapeutic agent.

Sustained or continuous administration of the antibody constructs of the invention may be intravenous or subcutaneous via a fluid delivery device or a small pumping system containing a fluid delivery mechanism to remove fluid from a reservoir and an actuator to actuate the delivery mechanism. Subcutaneous pump systems may include a needle or cannula for penetrating a patient's skin and delivering a single composition into the patient's body. Said pumping systems can be directly fixed or affixed to the patient's skin independently of a vein, artery or blood vessel, thereby providing direct contact between the pumping system and the patient's skin. The pump system can be attached to the patient's skin from 24 hours to several days. The pumping system can be small in size with a reservoir for small volumes. As a non-limiting example, the volume of the reservoir for a suitable pharmaceutical composition to be administered may be from 0.1 to 50 ml.

Long-term administration can also be transdermal by patching the skin and changing at intervals. One of skill in the art is aware of drug delivery patch systems suitable for this purpose. It should be noted that transdermal administration is particularly suitable for continuous administration, since the exchange of the first expended patch can be successfully carried out simultaneously with the placement of a new second patch, for example, on the surface of the skin immediately adjacent to the first expended patch and immediately before the removal of the first expended patch. There are no problems with flow interruption or battery failure.

If the pharmaceutical composition is lyophilized, the lyophilized material is first reconstituted in an appropriate liquid prior to administration. The lyophilized material can be reconstituted in, for example, bacteriostatic water for injection (BWFI), physiological saline, phosphate buffered saline (PBS), or in the same composition that the protein was in prior to lyophilization.

The compositions of this invention may be administered to a subject at a suitable dose, which can be determined, for example, by dose escalation studies when administering increased doses of an antibody construct of the invention exhibiting cross-species specificity as described herein to primates other than chimpanzees, for example, macaques. As indicated above, the antibody construct of the invention exhibiting cross-species specificity as described herein can advantageously be used in an identical form in preclinical studies in non-chimpanzee primates and as a drug in humans. The dosage regimen will be determined by the attending physician and clinical factors. As is well known in the medical field,

- 56 041992 dosage for any patient depends on many factors, including the anthropometric data of the patient, body surface area, age, specific compound to be administered, sex, time and route of administration, general health, and other drugs that are administered simultaneously.

The term effective dose or effective dosage is defined as an amount sufficient to achieve or at least partially achieve the desired effect. The term therapeutically effective dose is defined as an amount sufficient to treat or at least partially arrest a disease and its complications in a patient already suffering from the disease. Amounts or doses effective for this use will depend on the condition being treated (indication), the antibody design being set, the therapeutic context and goals, the severity of the disease, prior therapy, the patient's medical history and response to the therapeutic agent, route of administration, size (weight body area or organ size) and/or the condition (age and general health) of the patient, as well as the general condition of the patient's own immune system. The correct dose may be adjusted according to the judgment of the attending physician so that it may be administered to the patient one or more times over several administrations and to achieve the optimum therapeutic effect.

A typical dosage may be in the range of about 0.1 μg/kg to about 30 mg/kg or more, depending on the above factors. In specific embodiments of the invention, the dosage may correspond to the range from 1.0 μg/kg to about 20 mg/kg, in some cases, from 10 μg/kg to about 10 mg/kg, or from 100 μg/kg to about 5 mg/kg .

A therapeutically effective amount of an antibody construct of the invention preferably results in a reduction in the severity of symptoms of the disease, an increase in the frequency or duration of periods without symptoms of the disease, or the prevention of deterioration or disability due to the disease. For the treatment of CD70-expressing tumors, a therapeutically effective amount of an antibody construct of the invention, e.g., an anti-CD70/anti-CD3 antibody, preferably inhibits cell or tumor growth by at least about 20%, at least about 40%, at least at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% compared to untreated patients. The ability of a compound to inhibit tumor growth can be evaluated in an animal model predictive of efficacy in human tumors.

The pharmaceutical composition can be administered as a single therapeutic agent or in combination with additional therapies such as anti-cancer therapies as needed, eg other protein and non-protein drugs. These drugs can be administered simultaneously with a composition containing an antibody construct of the invention as defined herein, or separately before or after administration of said antibody construct at timely defined intervals and doses.

As used herein, the term effective and non-toxic dose refers to the tolerable dose of an antibody construct of the invention that is high enough to cause depletion of pathological cells, tumor eradication, tumor shrinkage, or disease stabilization without or substantially without significant toxic effects. Such effective and non-toxic doses can be determined, for example, using dose escalation studies described in the art, and should be below the dose causing serious adverse side effects (dose limiting toxicity - DLT).

As used herein, the term toxicity refers to the toxic effects of a drug product resulting in adverse events or severe adverse events. These side effects may relate to the lack of tolerability of the drug in general and / or the lack of local tolerance after administration. Toxicity may also include teratogenic or carcinogenic effects caused by the drug.

The term safety, in vivo safety, or tolerability, as used herein, defines the administration of a drug without causing serious side effects immediately after administration (local tolerance) and over a longer period of drug use. Safety, in vivo safety or tolerability can be assessed, for example, at regular intervals during the treatment and follow-up period. Measurements include clinical assessment, such as organ manifestations and screening for laboratory abnormalities. Clinical evaluation can be performed and abnormal results recorded/coded according to NCI-CTC and/or MedDRA standards. Organ manifestations may include criteria such as allergy/immunology, blood/bone marrow, cardiac arrhythmia, coagulation, and the like, as specified, for example, in the Common Criteria for Adverse Events v3.0 (CTCAE). Laboratory parameters that may be tested include, for example, hematology, clinical chemistry, coagulation profile, and urinalysis and examination of other body fluids such as serum, plasma, lymphoid or spinal fluid, cerebrospinal fluid, and the like. Thus, safety can be assessed, for example, by physical examination, imaging techniques (i.e. ultrasound, x-ray, computed tomography, magnetic resonance imaging).

- 57 041992 graphics (MRI), other measurements using technical devices (eg electrocardiogram), vital signs, by measuring laboratory parameters and registering adverse events. For example, adverse events in non-chimpanzee primates in the uses and methods of the invention can be investigated by histopathological and/or histochemical methods.

The above terms are also mentioned, for example, in Preclinical safety evaluation of biotechnology-derived Pharmaceuticals S6; ICH Harmonised Tripartite Guideline; ICH Steering Committee meeting on July 16, 1997.

In yet another embodiment, the invention provides a kit comprising an antibody construct of the invention, an antibody construct prepared according to a method of the invention, a polynucleotide/nucleic acid molecule, a vector of the invention, and/or a host cell of the invention.

In the context of this invention, the term kit means two or more components, one of which corresponds to an antibody construct, pharmaceutical composition, vector, or host cell of the invention, packaged together in a container, reservoir, or the like. Thus, a kit can be described as a set of products and/or tools that are sufficient to achieve a specific purpose and that can be sold as a unit.

The kit may contain one or more reservoirs (such as vials, ampoules, containers, syringes, bottles, bags) of any suitable shape, size and material (preferably waterproof, such as plastic or glass) containing the antibody construct or pharmaceutical composition of this invention in appropriate dosage for administration (see above). The kit may additionally contain instructions for use (for example, in the form of a brochure or instructions for use), means for administering the antibody construct of this invention, such as a syringe, pump, infusor, or the like, a means for reconstituting the antibody construct of the invention, and/or a means to dilute the antibody construct of the invention.

The invention also provides single dose kits for administration. The kit of the invention may also include a first reservoir containing a dry/lyophilized antibody construct and a second reservoir containing an aqueous composition. In some embodiments, implementation of the present invention provides kits containing single-chamber and multi-chamber pre-filled syringes (eg, syringes with liquid and syringes with lyophilisate).

Brief description of graphic materials

Fig. 1.

Expression control of constructs used for epitope mapping on CHO cells using an anti-V5 antibody. See example 1.

Fig. 2.

Schematic representation of multiplex epitope binding or competition analysis and FACS reading. 14 beads are pre-coated, each with a separate antibody. A second antibody X is added and additional binding determined. If no additional binding can be determined, the antibodies compete for binding with each other.

Fig. 3.

Experimental set-up for epitope mapping analysis, see Example 2. As indicated, the V5 tag is fused to a glycine/serine linker at the C-terminus of the chimeric molecules.

Fig. 4.

The result of epitope mapping of several exemplary CDB-specific CD70xCD3 binding domains in scFc format performed as described in Example 2. Although not specifically indicated in FIG. 4A and 4B, all constructs were CD70xCD3 (I2C) bispecific and in scFc format. The x-axis depicts comparison. PE-A (PE=Phycoerythrin, A=Signal Area) and the y-axis represents quantities (events) normalized to regimen.

Fig. 5.

Bispecific binding, cross-species cross-specificity, and no binding to the human CD40L paralog of CD70 presented for a representative number of scFc format antibody constructs as described in Examples 5 and 6. X-axis depicts comparison. PE-A (PE=phycoerythrin, A=signal area) and the y-axis displays quantities (events).

Fig. 6.

The cytotoxic activity of CD70-21D_CCxI2C-scFc was analyzed in a FACS-based cytotoxicity assay using CHO cells transfected with human CD70 as target cells and unstimulated human PBMC as effector cells. The analysis was carried out as described in example 8.5. In a parallel approach, soluble CD27 was added at a concentration of 1 ng/ml. The presence of a soluble form of CD27 did not impair the cytotoxic activity of the tested antibody construct.

- 58 041992

Examples

The following examples illustrate the invention. These examples are not to be construed as limiting the scope of the present invention. This invention is limited only by the claims.

Example 1

Generation of CHO cells expressing wild-type and truncated CD70.

The extracellular domain of the CD70 antigen can be divided into various subdomains or regions of E1-E7, which are defined for the purposes of examples 1 and 2 by the following amino acid positions:

El ak 43-62 SEQ ID NO: 743 E2 ak 63-84 SEQ ID NO: 744 ЕЗ ak 85-109 SEQ ID NO: 745 E4 ak 110-134 SEQ ID NO: 746 E5 ak 135-151 SEQ ID NO: 747 E6 ak 152-175 SEQ ID NO: 748 E7 ak 176-193 SEQ ID NO: 749 El+2 ak 43-84 SEQ ID NO: 750 E3+4 ac 85-134 SEQ ID NO: 751 E4+5 acc 110-151 SEQ ID NO: 752 E5+6 acc 135-175 SEQ ID NO: 753 E6+7 acc 152-193 SEQ ID NO: 754

For the construction of chimeric human/mouse CD70 molecules used for epitope mapping (Example 2), the sequences of the corresponding seven human regions as well as five combinations of two adjacent human regions (see above) were replaced with the corresponding mouse CD70 regions. In addition, the V5 tag (GKPIPNPLLGLDST) was fused via a GGGGS linker to the C-terminus of the chimeric molecules. The final sequences of the chimeric molecules are shown in SEQ ID NO: 759768. In addition, full-length human CD70 (SEQ ID NO: 741) and full-length mouse CD70 (SEQ ID NO: 757) were constructed, both of which have the V5 tag (GKPIPNPLLGLDST) fused through a GGGGS linker with their C-terminus.

To generate CHO dhfr cells expressing the above constructs, the appropriate coding sequences were cloned into a plasmid designated pEF-DHFR (pEF-DHFR is described in Raum et al. Cancer Immunol Immunother 50 (2001) 141-150). CHO cells transfected with human CD70 but without the V5 label were also generated. All cloning procedures were performed according to standard protocols (Sambrook, Molecular Cloning; A Laboratory Manual, 3rd edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York (2001)). For each construct, the appropriate plasmid was transfected into DHFR-deficient CHO cells for eukaryotic expression as described in Kaufman R.J. (1990) Methods Enzymol. 185, 537-566.

Expression of the constructs on CHO cells was tested using anti-v5 mouse IgG2a monoclonal antibody (1 μg/ml, Serotec AbD, no. MCA 1360). Bound monoclonal antibody was detected using anti-mouse IgG Fc-gamma-PE. As a negative control, cells were incubated with the control antibody isotype instead of the first antibody. Samples were analyzed by flow cytometry. The CHO transfectants did not express only E5 or E5+6. See fig. 1.

Example 2

Epitope mapping of anti-CD70 antibody constructs.

CHO cells prepared as described in Example 1 were stained with a crude, undiluted periplasmic extract containing single anti-CD70 scFv molecules. Bound scFvs were detected with mouse anti-FLAG monoclonal antibody M2 (1 μg/ml, Sigma F1804) followed by anti-mouse IgG Fc-gamma-PE (1:100; Jackson Immunoresearch no. 115-116-071). All antibodies were diluted in PBS/1.5% FCS. As a negative control, cells were incubated with PBS/2% FCS (fetal calf serum) instead of periplasmic extract. Samples were analyzed by flow cytometry. Although all tested anti-CD70 scFv molecules could bind to human CD70 without V5 tag (strong FACS signal), none could bind to mouse CD70 (no FACS signal).

The binding domains were classified into different groups (I, II, III, IIIv, V, VI, VII and VIII) depending on the chimeric CD70 molecule for which binding loss was observed. The loss of binding is in most cases complete, but in some cases it can also be partial. Partial loss of binding was observed in particular for the region designated E6 (see Groups II, IIIv, VI and VIII), but in some cases also for other regions. For some binding domains tested, the results obtained with the combination of two neighboring regions (E1+2, E3+4, E4+5, E6+7) were not always clear. Thus, the classification into different groups was mainly due to

- 59 041992 results obtained with these chimeric molecules having only one region replaced by a mouse analogue region. The results are presented below in table. 4.

Table 4

Several regions of the extracellular domain of CD70 (E2, E3, E4, E6 and combinations thereof) have been identified as containing an epitope recognized by the respective anti-CD70 binding molecules detected with complete or partial loss of FACS signal. The designation of groups and linking domains is also used in the sequence listing.

Group* Signal loss in these chimeric molecules: Region specific CD70 binding domain: Binding domain designation: CD70-x* I E2, E3, E4, E6 E1+2, E3+4, E4+5, E6+7 E2/E3/E4/E6 x=4, 7, 9, 13, 35, 44, 45, 47, 48, 49, 50, 52, 57, 61, 62, 65, 67, 68, 73 II E2, E3, E4, (E6 partially) Е1+2, ЕЗ+4, Е4+5 E2/E3/E4/(E6) x=2, 8, 14, 15, 16, 17, 18, 20, 26, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 40, 41, 42, 43, 46, 53, 58, 59, 63, 66, 74 III E2, E3, E6 Е1+2, Е6+7 E2/E3/E6 x=1, 11 IIIv E2, E3, (E6 partially) E2/E3/(E6) x=3 V E3, E4, E6 E3+4, E4+5, E6+7 E3/E4/E6 x=12 VI E3, E4, (E6 partially) E3+4, E4+5 E3/E4/(E6) x=19, 21, 22, 23, 24, 25, 27, 39, 51, 54, 64, 69 VII huCD70-V5 and all chimeric horse riding label V5 inhibits binding x=55, 56, 60, 70, 71, 72 VIII E3, (E6 partially) E3/(E6) x=5, 6, 10

None of the anti-CD70 scFv molecules showed loss of binding to the chimeric E1 or E7 molecule. Therefore, the first binding domain of the antibody constructs of the invention does not appear to bind to the epitope contained in the region indicated by E1 and does not appear to bind to the epitope contained in the region indicated by E7. In group VII, it appears that the presence of the V5 label in the chimeric molecules prevents binding of anti-CD70 scFv molecules. Therefore, the epitope cannot be determined. It can be assumed that this group of anti-CD70 scFv molecules binds to the epitope contained in the region labeled E7, since this region is adjacent to the V5 label.

In FIG. 3 shows the experimental setup, and FIG. 4A and B show the result of epitope mapping of several exemplary bispecific binding domains in scFc format.

Example 3

Determination of the affinity of antibodies to human and macaque CD70 and CD3 based on Biacore and Octet.

Biacore assay experiments were performed using recombinant human/macaque CD70-ECD fusion proteins with albumin to determine target binding of antibody constructs of the invention.

In detail, CM5 Sensor Chips (GE Healthcare) were immobilized with approximately 600-800 RU of the respective recombinant antigen using acetate buffer pH 4.5 according to the manufacturer's instructions. Samples of the bispecific CD70xCD3 antibody construct were loaded in dilution series at the following concentrations: 50 nM, 25 nM, 12.5 nM, 6.25 nM and 3.13 nM diluted in HBS-EP buffer (GE Healthcare). The flow rate was 30 μl/min for 3 min, then running buffer HBS-EP was applied again for 8-20 min at a flow rate of 30 μl/ml. Chip regeneration was performed using 10 mM glycine solution 10 mM NaCl pH 1.5. The datasets were analyzed using the BiaEval software. In general, two independent experiments were carried out.

Biacore, Octet assay experiments were performed using recombinant CD70-NHS-PEG human/macaque biotin fusion with albumin to determine binding of const targets.

- 60 041992 Antibodies according to the invention. In detail, the streptavidin ends are immobilized with approximately 0.1-0.2 nm of the appropriate recombinant antigen according to the manufacturer's guidelines. Samples of the bispecific CD70xCD3 antibody construct were prepared in a dilution series of the following concentrations: 300 nM, 150 nM, 75 nM, 37.5 nM, 18.8 nM and 9.4 nM diluted in HBS-EP buffer (GE Healthcare). For each dilution, one streptavidin end was immobilized with antigen. Binding was measured in a black 96-well MTP, flow rate was 1000 rpm for 8 minutes. For dissociation, the ends were incubated in HBS-EP running buffer for 15-30 min, again at a flow rate of 1000 rpm. The datasets were analyzed using ForteBio Data Analysis software. In general, two independent experiments were carried out.

The CD70xCD3 bispecific antibody constructs analyzed in scFc format showed very high affinity for human CD70 in the 1-digit nanomolar range (except for one construct in the very low two-digit nanomolar range) as determined by the Octet assay. Binding to macaque CD70 was balanced, also showing affinity in the 1 digit nanomolar range. The affinity values, as well as the calculated affinity gap, are presented in Table 1. 5.

Table 5

Affinities of CD70xCD3 (I2C) bispecific antibody constructs against human and macaque CD70 determined by Octet analysis and calculated interspecies affinity gaps. All constructs were measured in two independent experiments using dilution series, except for those marked with (*) which were measured in only one experiment.

Bispecific constructs of CD70xCD3 antibodies Affinity based on human Octet CD70 assay [nM] Affinity based on macaque Octet CD70 assay [nM] Affinity gap KD max/KD pers CD70-13D_CCxI2C-scFc 5.84 ± 1.07 5.41 ± 2.33 0.93 CD70-16D_CCxI2C-scFc 2.80 + 1.30 0.60* 0.21 CD70-21D_CCxI2C-scFc 0.81 ± 0.42 0.34* 0.42 CD70-24D_CCxI2C-scFc 12.75±0.35 8.75 ± 4.74 0.69 CD70-25D_CCxI2C-scFc 1.51 + 0.43 1.57 + 0.82 1.04 CD70_l-G2D_CCxI2C-scFc 2.35 ± 0.42 1.44 ± 0.32 0.61 CD70-27D_CCxI2C-scFc 5.84 ± 1.18 5.31 ± 0.22 0.91 CD70-28D_CCxI2C-scFc 5.50±0.59 7.87 ± 0.78 1.43 CD70-31D_CCxI2C-scFc 5.44 ± 2.52 7.45 ± 1.03 1.37 CD70-32D_CCxI2C-scFc 4.07 ± 0.28 4.96±0.57 1.22 CD70-42D_CCxI2C-scFc 2.56 ± 0.13 4.46±0.35 1.74 CD70-43D_CCxI2C-scFc 6.92 ± 1.27 5.82 ± 2.26 0.84 CD70-48D_CCxI2C-scFc 2.12±0.02 3.38±0.10 1.59 CD70-62D_CCxI2C-scFc 3.05±0.04 3.35±0.43 1.10 CD70-23D_CCxI2C-scFc 2.58 ± 0.23 2.57 ± 0.12 1.00

In addition, binding of the bispecific antibody constructs to human CD3 and macaque CD3 as well as human and macaque FcRn was confirmed in the Biacore assay and shown to be strong and well balanced. The analyzed CD70xCD3 bispecific antibody constructs in scFc format showed high affinity for human CD3 in the very low 2-digit or 1-digit nanomolar range. Binding to macaque CD3 was balanced, also showing affinities in similar ranges. The affinity values, as well as the calculated affinity gap, are presented in Table 1. 6.

- 61 041992

Table 6

Affinities of CD70xCD3 (I2C) bispecific antibody constructs against human and macaque CD3 determined by Biacore analysis and calculated interspecies affinity gaps

Bispecific constructs of CD70XCD3 antibodies Affinity based on human Biacore CD3 assay [nM] Affinity based on macaque Biacore CD3 assay [nM] Affinity gap KD max/KD pers CD70-13D_CCxI2C-scFc 13.35±0.78 11.05±0.64 0.83 CD70-16D_CCxI2C-scFc 14.05±0.64 12.50±1.84 0.89 CD70-21D_CCxI2C-scFc 12.60±0.28 10.65±0.35 0.85 CD70-24D_CCxI2C-scFc 13.15 ± 1.48 10.70±1.41 0.81 CD70-25D_CCxI2C-scFc 12.75±2.05 10.39±2.14 0.81 CD70_l-G2D_CCxI2C-scFc 12.95±0.35 10.75±0.21 0.83 CD70-27D_CCxI2C-scFc 12.20±2.26 10.05 ± 2.19 0.82 CD70-28D_CCxI2C-scFc 10.13 ± 1.66 8.56 ± 1.48 0.85 CD70-31D_CCxI2C-scFc 14.60±1.13 12.22±0.99 0.84 CD70-32D_CCxI2C-scFc 13.55 ± 1.91 11.40±1.70 0.84 CD70-42D_CCxI2C-scFc 8.13 ± 0.21 7.96±1.50 0.98 CD70-43D_CCxI2C-scFc 8.21±0.76 6.81 ± 0.74 0.83 CD70-48D_CCxI2C-scFc 10.64 ± 1.22 9.09±0.83 0.85 CD70-62D_CCxI2C-scFc 9.02 ± 1.20 7.67 ± 1.17 0.85 CD70-23D_CCxI2C-scFc 11.70 ± 1.13 9.65 ± 1.06 0.82

Example 4

Scatchard-based specificity analysis of the CD70xCD3 bispecific anti-human and macaque CD70 antibody construct on target antigen-positive cells and determination of the interspecies affinity gap.

The affinities of CD70xCD3 bispecific antibody constructs to CHO cells transfected with human or macaque CD70 were also determined using the Scatchard assay as the most reliable method to measure the potential affinity gap between human and macaque CD70. For Scatchard analysis, binding saturation experiments were performed using a monovalent detection system to accurately determine the monovalent binding of the CD70xCD3 bispecific antibody constructs to the respective cell line.

2 x 10 ⁴ cells of the respective cell line (CHO cell line expressing recombinant human CD70, CHO cell line expressing recombinant macaque CD70) were each incubated with 50 μl of a triplet dilution series (twelve dilutions at 1:2) of the respective CD70xCD3 bispecific antibody construct (until saturation was reached). ), starting at 10-20 nM, followed by incubation for 16 h at 4°C with stirring and one step of washing the residue. The cells were then incubated for another hour with 30 μl of the CD3xALEXA488 conjugate solution. After one washing step, cells were resuspended in 150 µl of FACS buffer containing 3.5% formaldehyde, incubated for another 15 min, centrifuged, resuspended in FACS buffer and analyzed using a FACS CantoII machine and FACS Diva software. Data were obtained from two independent sets of experiments, each of which used three repetitions. The corresponding Scatchard analysis was calculated to extrapolate the maximum binding (Bmax). The concentrations of the CD70xCD3 bispecific antibody constructs at half-maximal binding were determined, reflecting the respective KDs. Triple measurements were presented as hyperbolic curves and as S-curves to demonstrate the correct concentration from minimal to optimal binding.

The results are presented in table. 7 for a representative number of antibody constructs in scFc format. Scatchard's cell-based analysis confirmed that the CD70xCD3 bispecific antibody constructs of the invention in the low nanomolar range have affinity for human CD70 and macaque CD70 and present a small and very favorable cross-species affinity gap of about 1.

- 62 041992

Table 7

Affinities (KD) of the CD70xCD3 bispecific antibody constructs determined by Scatchard cell analysis with a calculated macaque KDCD70/human CD70 KD affinity gap. Antibody constructs were measured in two independent experiments, each used three times.

Bispecific constructs of CD70XCD3 antibodies Affinity based on human CD70 cells [nM] Affinity based on macaque CD70 cells [nM] Affinity gap KD max/KD pers CD70-13D_CCxI2C-scFc 7.64 ± 1.20 7.22±1.60 0.95 CD70-16D_CCxI2C-scFc 6.93±1.61 7.71 ± 1.74 1.11 CD70-21D_CCxI2C-scFc 10.77±0.98 11.63 ± 1.22 1.08 CD70-24D_CCxI2C-scFc 8.30±2.75 11.76±2.55 1.42 CD70-25D_CCxI2C-scFc 11.08 ± 4.74 12.57 ± 2.02 1.13 CD70_l-G2D_CCxI2CscFc 10.56±1.25 9.80±0.73 0.93 CD70-27D_CCxI2C-scFc 9.19±0.54 10.53±0.98 1.15 CD70-28D_CCxI2C-scFc 8.04 ± 1.73 7.18±0.45 0.89 CD70-31D_CCxI2C-scFc 9.40±0.78 10.54 ± 1.51 1.12 CD70-32D_CCxI2C-scFc 9.26 ± 4.36 7.56 ± 0.78 0.82 CD70-42D_CCxI2C-scFc 9.08 ± 2.21 9.15±0.16 1.01 CD70-43D_CCxI2C-scFc 8.73 ± 3.56 9.14 ± 5.73 1.05 CD70-48D_CCxI2C-scFc 6.64±0.13 6.56±0.50 0.99 CD70-62D_CCxI2C-scFc 4.02±0.12 5.17 ± 1.61 1.29 CD70-23D_CCxI2C-scFc 4.72±0.11 6.58±0.85 1.39

Example 5

Bispecific binding and interspecies cross-reactivity.

To confirm binding to human CD70 and CD3 and macaque CD70 and CD3, the bispecific antibody constructs of the invention were tested by flow cytometry using CHO cells transfected with human CD70 and macaque CD70, respectively, of the CD70-positive human ovarian carcinoma cell line OVCAR 8 (but other CD70-positive human cell lines are also possible, such as the clear cell renal adenocarcinoma cell line 0-786) the CD3-expressing HPB-all human leukemia T cell line (DSMZ, Braunschweig, ACC483) and the LnPx 4119 T cell line that expresses macaque CD3.

For flow cytometry, 200,000 cells of the respective cell lines were incubated for 60 min at 4°C with 50 μl of purified bispecific antibody construct at a concentration of 5 μg/ml. Cells were washed twice in PBS/2% FCS and then incubated with mouse native antibody (2 μg/ml) specific for the CD3 binding portion of the bispecific antibody constructs for 30 min at 4°C. After washing, binding mouse antibodies were detected with goat anti-mouse Fcy-PE (1:100) for 30 min at 4°C. Samples were measured using flow cytometry. Untransfected CHO cells were used as a negative control.

The results are shown in FIG. 5A-5C for a representative number of scFc antibody constructs. All tested CD70xCD3 constructs stained CHO cells transfected with human CD70 and macaque CD70, and they also stained the CD70 positive renal clear cell adenocarcinoma cell line 0-786 (natural expression). Human and macaque T cell lines expressing CD3 were also recognized by bispecific antibody constructs. In addition, there was no staining of negative control cells (CHO cells transfected with human CD40L and non-transfected CHO cells).

Example 6

Confirmation of the absence of binding to human paralogs.

Human CD40L paralog CD70 was stably transfected into CHO cells. The sequences of the paralog used in this example are indicated in the sequence listing (SEQ ID NO: 769). Protein expression was confirmed in FACS assays with specific antibodies. Flow cytometry analysis was performed as described in Example 5. The results are shown in FIG. 5A-C and are also mentioned in Example 5. The analysis confirmed that none of the CD70xCD3 bispecific antibody constructs of the invention cross-react with the human CD40L CD70 paralog.

- 63 041992

Example 7

Identity to the human germline.

To analyze the identity/sequence similarity of human germline antibody constructs, the CD70 binding domains of the invention were aligned as follows: Full VL, including all CDRs, was aligned; the full VH, including CDRs 1 and 2, but other than CDR3, was aligned to human antibody germline (Vbase) genes. More details can be found in the description of this application. The results are presented below in table. 8. All variants showed high germline similarity.

Table 8

Percent identity of VH and VL to human germline

Bispecific constructs of CD70xCD3 antibodies % identity to human germline [VH] % identity to human germline [VL] CD70-13D_CCxI2C-scFc 92.86 95.51 CD70-16D_CCxI2C-scFc 93, 88 97.75 CD70-21D_CCxI2C-scFc 92.86 96, 63 CD70-24D_CCxI2C-scFc 94, 90 98.88 CD70-25D_CCxI2C-scFc 93, 88 97.75 CD70_l-G2D_CCxI2CscFc 93, 88 96, 63 CD70-27D_CCxI2C-scFc 94, 90 96, 63 CD70-28D_CCxI2C-scFc 94, 90 95.51 CD70-31D_CCxI2C-scFc 91, 84 94.38 CD70-32D_CCxI2C-scFc 92.86 95.51 CD70-42D_CCxI2C-scFc 94, 90 96, 63 CD70-43D_CCxI2C-scFc 92.86 96, 63 CD70-48D_CCxI2C-scFc 90, 82 95.45 CD70-62D_CCxI2C-scFc 92.86 97.73

Example 8

cytotoxic activity.

The activity of the CD70xCD3 bispecific antibody constructs of the invention in redirecting effector T cells against CD70-expressing target cells was analyzed in five in vitro cytotoxicity assays.

The activity of CD70xCD3 bispecific antibody constructs in redirecting stimulated human CD8+ effector T cells against human CD70 transfected CHO cells was measured in an 18-hour 51-chromium release assay.

The efficacy of CD70xCD3 bispecific antibody constructs in redirecting stimulated human CD8+ effector T cells against the CD70-positive human ovarian carcinoma cell line OVCAR 8 (as well as other CD70-positive human cell lines are also possible) was measured in an 18-hour 51-chromium release assay.

The activity of the CD70xCD3 bispecific antibody constructs in redirecting T cells in unstimulated human PBMCs against human CD70 transfected CHO cells was measured in a 48-hour FACS-based cytotoxicity assay.

The activity of CD70xCD3 bispecific antibody constructs in targeting T cells in unstimulated human PBMCs against the CD70-positive human ovarian carcinoma cell line OVCAR 8 (but other CD70-positive human cell lines are possible) was measured in a 48-hour FACS-based cytotoxicity assay.

To confirm that cross-reactive CD70xCD3 bispecific antibody constructs are capable of redirecting macaque T cells against macaque CD70 transfected CHO cells, a 48 hour FACS-based cytotoxicity assay was performed using a macaque T cell line as effector T cells.

Example 8.1.

Chromium release assay with stimulated human T cells.

Stimulated T cells enriched for CD8+ T cells were generated as described below. A Petri dish (diameter 145 mm, Greiner bio-one GmbH, Kremsmunster) was coated with a commercially available specific anti-CD3 antibody (OCTS, Orthoclone) at a final concentration of 1 μg/ml for 1 hour at 37°C. Unbound protein was removed with a single PBS wash. 3-5x107 human PBMCs were added to a pre-coated petri dish in 120 ml RPMI 1640 stabilized glutamine/10% FCS/IL-2 20 U/ml (Proleukin®, Chiron) and stimulated for 2 days. On the third day

- 64 041992 cells were harvested and washed once with RPMI 1640. IL-2 was added to a final concentration of 20 U/ml and the cells were cultured again for one day in the same cell culture medium as above. CD8+ cytotoxic T lymphocytes (CTLs) were enriched by depletion of CD4+ T cells and CD56+ NK cells using Dynal-Beads according to the manufacturer's protocol.

CHO target cells transfected with macaque CD70 or human CD70 were washed twice with PBS and labeled with 11.1 MBq ⁵¹ Cr in a final volume of 100 μl RPMI with 50% FCS for 60 min at 37°C. The labeled target cells were then washed 3 times with 5 ml RPMI and then used in the cytotoxicity assay. The assay was performed on a 96-well plate in a total volume of 200 μl supplemented with RPMI with an E:T ratio of 10:1. An initial concentration of 0.01-1 μg/ml of purified bispecific antibody construct and three-fold dilutions were used. The incubation time for the assay was 18 hours. Cytotoxicity was defined as the relative values of released chromium in the supernatant relative to the difference between maximum lysis (addition of Triton-X) and spontaneous lysis (no effector cells). All measurements were carried out in four repetitions. Chromium activity in supernatants was measured on a Wizard 3 gamma counter (Perkin Elmer Life Sciences GmbH, Cologne, Germany). Results analysis was performed using Prism 5 for Windows (version 5.0, GraphPad Software Inc., San Diego, CA, USA). EC50 values calculated by the analysis program from sigmoidal dose response curves were used to compare cytotoxic activity.

Example 8.2.

Redirection activity of stimulated human effector T cells against CHO cells transfected with human CD70.

The cytotoxic activity of the CD70xCD3 bispecific antibody constructs of the invention was analyzed in a 51-chromium ( ⁵¹ Cr) releasing cytotoxicity assay using human CD70-transfected CHO cells as target cells and stimulated human CD8+ T cells as effector cells. The experiment was carried out as described in example 8.1.

The results are presented in table. 9 for a representative number of scFc antibody constructs. The CD70xCD3 (I2C) bispecific antibody constructs showed very potent cytotoxic activity against CD70-transfected CHO cells in the sub-picomolar range.

Table 9

EC50 [pg/mL] values of CD70xCD3 bispecific antibody constructs analyzed in a 51-chromium ( ⁵¹ Cr) releasing cytotoxicity assay using human CD70-transfected CHO cells as target cells and stimulated human CD8 T cells as effector cells

Bispecific constructs of CD70xCD3 antibodies EC50 [nM] CD70-13D_CCxI2C-scFc 0.07 CD70-16D_CCxI2C-scFc 0.005 CD70-21D_CCxI2C-scFc 0.06 CD70-24D_CCxI2C-scFc 0.15 CD70-25D_CCxI2C-scFc 0.01 CD70_l-G2D_CCxI2C-scFc 0.01 CD70-27D_CCxI2C-scFc 0.08 CD70-28D_CCxI2C-scFc 0.03 CD70-31D_CCxI2C-scFc 0.11 CD70-32D_CCxI2C-scFc 0.08 CD70-42D_CCxI2C-scFc 0.05 CD70-43D_CCxI2C-scFc 0.08 CD70-48D_CCxI2C-scFc 0.01 CD70-62D_CCxI2C-scFc 0.02 CD70-13D_CCxI2C-scFc 0.05

Example 8.3.

Redirecting activity of stimulated human effector T cells against a CD70 positive human cell line.

The cytotoxic activity of CD70xCD3 bispecific antibody constructs was analyzed in a 51-chromium ( ⁵¹ Cr) releasing cytotoxicity assay using the CD70-positive human ovarian carcinoma cell line OVCAR 8 as the source of target cells and stimulated human CD8+ T cells as effector cells. The analysis was carried out as described in example 8.1.

- 65 041992

The results are presented in table. 10 for a representative number of scFc antibody constructs. In accordance with the results of 51-chromium release studies with stimulated CD8+ enriched human T-lymphocytes as effector cells and human CD70-transfected CHO cells as target cells, the CD70xCD3 bispecific antibody constructs of the invention also greatly influence cytotoxic activity against naturally expressing cells. -targets with cytotoxic activity against natural expressing cells in the subpicomolar range.

Table 10

EC50 [pM] values of CD70xCD3 bispecific antibody constructs (I2C) analyzed in an 18-hour 51-chromium ( ⁵¹ Cr) releasing cytotoxicity assay using the CD70-positive human ovarian carcinoma cell line OVCAR 8 as target cell source, and stimulated CD8 enriched T cells human as effector cells

Bispecific constructs of CD70XCD3 antibodies EC50 [nM] CD70-13D_CCxI2C-scFc 0.14 CD70-16D_CCxI2C-scFc 0.06 CD70-21D_CCxI2C-scFc 0.10 CD70-24D_CCxI2C-scFc 1.39 CD70-25D_CCxI2C-scFc 0.24 CD70_l-G2D_CCxI2C-scFc 0.12 CD70-27D_CCxI2C-scFc 1.35 CD70-28D_CCxI2C-scFc 0.49 CD70-31D_CCxI2C-scFc 0.64 CD70-32D_CCxI2C-scFc 0.46 CD70-42D_CCxI2C-scFc 0.84 CD70-43D_CCxI2C-scFc 0.67 CD70-48D_CCxI2C-scFc 0.47 CD70-62D_CCxI2C-scFc 0.47 CD70-13D_CCxI2C-scFc 0.36

Example 8.4.

FACS-based cytotoxicity assay with unstimulated human PBMC.

Isolation of effector cells.

Human peripheral blood mononuclear cells (PBMCs) were obtained by ficoll density gradient centrifugation from enriched preparations of lymphocytes (buffered sheaths), a by-product of blood banks that collect blood for transfusion. The buffy coats were supplied by the local blood bank and the PBMCs were prepared on the same day of blood collection. After centrifugation in a ficoll gradient and extensive washes with PBS Dulbecco (Gibco), remaining erythrocytes were removed from the PBMC by incubation with erythrocyte lysis buffer (155 mM NH ₄ Cl, 10 mM KHCO 3 , 100 μM EDTA). Platelets were removed through the supernatant by centrifuging the PBMC at 100xg. The remaining lymphocytes mainly cover B and T lymphocytes, NK cells and monocytes. PBMCs were maintained in culture at 37°C/5% CO2 in RPMI medium (Gibco) with 10% FCS (Gibco).

Depletion of CD14+ and CD56+ cells.

CD14 microbeads (Milteny Biotec, MACS, no. 130050-201) were used to deplete CD14+ cells; human CD56 microbeads (MACS, no. 130-050-401) were used to deplete NK cells. PBMC were counted and centrifuged for 10 min at room temperature with 300xg. The supernatant was discarded and the cell pellet was resuspended in MACS isolation buffer [80 μl/10 ⁷ cells; PBS (Invitrogen, no. 20012-043), 0.5% (v/v) FBS (Gibco, no. 10270-106), 2 mM EDTA (Sigma-Aldrich, no. E6511)]. CD14 microbeads and CD56 microbeads (20 μl/10 ⁷ cells) were added and incubated for 15 min at 4-8°C. Cells were washed with MACS isolation buffer (1-2 ml/10 ⁷ cells). After centrifugation (see above), the supernatant was discarded and the cells were resuspended in MACS isolation buffer (500 μl/10 ⁸ cells). CD14/CD56 negative cells were then isolated using LS Columns (columns for liquid chromatography) (Miltenyi Biotec, no. 130-042-401). Cells RVMS wt./about. CD14+/CD56+ were cultured in complete RPMI medium, ie. RPMI1640 (Biochrom AG, no. FG1215) supplemented with 10% PBS (Biochrom AG, no. S0115), 1x essential amino acids (Biochrom AG, #K0293), 10 mM Hepes buffer (Biochrom AG, no. L1613), 1 mM sodium pyruvate (Biochrom AG , no. L0473) and 100 U/ml penicillin/streptomycin (Biochrom AG, no. A2213) at 37°C in an incubator, as needed.

Labeling of target cells.

A fluorescent meme was used to analyze cell lysis in flow cytometry assays.

- 66 041992 DiOC ₁₈ (DiO) brane dye (Molecular Probes, no. V22886) for labeling CHO cells transfected with human CD70 or macaque CD70 as target cells and distinguishing them from effector cells. Briefly, cells were harvested, washed once with PBS and adjusted to 10 ⁶ cells/ml in PBS containing 2% (v/v) FBS and the DiO membrane dye (5 μl/10 ⁶ cells). After incubation for 3 min at 37° C., the cells were washed twice in complete RPMI medium and the cell number was adjusted to 1.25 x 10 ⁵ cells/ml. Cell viability was determined using 0.5% (v/v) EosinG isotonic solution (Roth, no. 45380).

Analysis based on flow cytometry.

This assay was designed to quantify the lysis of CHO cells transfected with human CD70 and macaque CD70 in the presence of serial dilutions of anti-CD70 bispecific antibody constructs. Equal volumes of DiO-labeled target cells and effector cells (ie, PBMC w/v CD14+ cells) were mixed to give an E:T cell ratio of 10:1. 160 μl of this suspension was transferred to each well of a 96-well plate. 40 µl serial dilutions of CD70xCD3 antibody bispecific constructs and a negative control bispecific construct (a CD3-based antibody bispecific construct recognizing an irrelevant target antigen) or complete RPMI medium were added as an additional negative control. The cytotoxic reaction mediated by the bispecific antibody proceeded for 48 h in a humidified incubator with 7% CO ₂ . The cells were then transferred to a new 96-well plate, and the integrity of the target cell membrane was monitored by adding propidium iodide (PI) at a final concentration of 1 μg/ml. PI is a membrane-impermeable dye that is normally eliminated from viable cells while dead cells accept it and become identifiable by fluorescent emission.

Samples were measured by flow cytometry on a FACSCanto II instrument and analyzed using FACSDiva software (both from Becton Dickinson). Target cells were identified as DiO positive cells. PI-negative target cells were classified as live target cells.

The percentage of cytotoxicity was calculated using the following formula:

^dead target cells

Cytotoxicity [%] = x 100 ft target cells n = number of events.

Using GraphPad Prism 5 software (Graph Pad software, San Diego), percent cytotoxicity was plotted against respective concentrations of the bispecific antibody constructs. Dose response curves were analyzed using four parametric logistic regression models to evaluate sigmoid dose response curves with a fixed hill slope and calculate an EC50 value.

Example 8.5.

Redirection activity of unstimulated human PBMCs against human CD70 transfected CHO cells.

The cytotoxic activity of the CD70xCD3 bispecific antibody constructs was analyzed in a FACS-based cytotoxicity assay using human CD70-transfected CHO cells as target cells and unstimulated human PBMC as effector cells. The analysis was carried out as described in example 8.4 above. In the next approach, soluble CD27 was added at a concentration of 1 ng/ml to test whether the presence of soluble form of CD27 would impair the cytotoxic activity of the test antibody constructs.

The results of FACS-based cytotoxicity assays are shown in Table 11 for a representative number of scFc format antibody constructs with unstimulated human PBMCs as effector cells and CHO cells transfected with human CD70 as targets. The presence of CD27 did not significantly affect the EC50 values. See also FIG. 6 showing the results for the CD70-21D_CCxI2C-scFc construct.

- 67 041992

Table 11

EC50 [pM] values of bispecific CD70xCD3 antibody constructs (I2C) analyzed in a 48-hour FACS-based assay using unstimulated PBMCs as effector cells and CHO cells transfected with human CD70 as target cells

Bispecific constructs of CD70xCD3 antibodies EC50 [nM] without SCD27 EC50 [pM] with 1 ng/mL SCD27 CD70-13D_CCxI2C-scFc 0.21 0.21 CD70-16D_CCxI2C-scFc 0.27 0.18 CD70-21D_CCxI2C-scFc 0.22 0.17 CD70-24D_CCxI2C-scFc 0.32 0.43 CD70-25D_CCxI2C-scFc 0.29 0.21 CD70_l-G2D_CCxI2C-scFc 0.49 0.25 CD70-27D_CCxI2C-scFc 0.49 0.29 CD70-28D_CCxI2C-scFc 0.19 0.20 CD70-31D_CCxI2C-scFc 0.48 0.60 CD70-32D_CCxI2C-scFc 0.26 0.24 CD70-42D_CCxI2C-scFc 0.29 0.23 CD70-43D_CCxI2C-scFc 0.22 0.15 CD70-48D_CCxI2C-scFc 0.26 0.29 CD70-62D_CCxI2C-scFc 0.35 0.21 CD70-13D_CCxI2C-scFc 0.25 0.18

It was expected that EC50 values were generally higher in cytotoxicity assays with unstimulated PBMCs as effector cells compared to cytotoxicity assays using stimulated human CD8+ T cells (see Example 8.2).

Example 8.6.

Redirection activity of unstimulated human PBMCs against a CD70-positive human ovarian carcinoma cell line.

The cytotoxic activity of CD70xCD3 bispecific antibody constructs was analyzed in a FACS-based cytotoxicity assay using the CD70-positive human ovarian carcinoma cell line OVCAR 8 as target cell source and unstimulated human PBMC as effector cells. The analysis was carried out as described in example 8.4 above. The results are shown in Table 12 for a representative number of scFc antibody constructs.

Table 12

EC50 [pM] values of bispecific CD70xCD3 antibody constructs (I2C) analyzed in a 48-hour FACS-based assay using unstimulated PBMCs as effector cells and human SHP-77 cell lines as target cells

Bispecific constructs of CD70xCD3 antibodies EC50 [nM] CD70-13D_CCxI2C-scFc 0.07 CD70-16D_CCxI2C-scFc 0.10 CD70-21D_CCxI2C-scFc 0.06 CD70-24D_CCxI2C-scFc 0.50 CD70-25D_CCxI2C-scFc 0.05 CD70_l-G2D_CCxI2C-scFc 0.08 CD70-27D_CCxI2C-scFc 0.56 CD70-28D_CCxI2C-scFc 0.12 CD70-31D_CCxI2C-scFc 1, 03 CD70-32D_CCxI2C-scFc 0.06 CD70-42D_CCxI2C-scFc 0.13 CD70-43D_CCxI2C-scFc 0.14 CD70-48D_CCxI2C-scFc 0.14 CD70-62D_CCxI2C-scFc 0.26 CD70-13D_CCxI2C-scFc 0.09

- 68 041992

Example 8.7.

Redirecting activity of macaque T cells against CHO cells transfected with macaque CD70.

Finally, the cytotoxic activity of CD70xCD3 bispecific antibody constructs was analyzed in a FACS-based cytotoxicity assay using macaque CD70 (supo) transfected CHO cells as target cells and the 4119LnPx macaque T cell line (Knappe et al. Blood 95:3256-61 (2000)) as effector cells. Target cell labeling of CHO cells transfected with macaque CD70 and analysis of cytotoxic activity based on flow cytometry were performed as described above.

The results are presented in table. 13 for a representative number of antibody constructs in scFc format. Macaque T cells from the 4119LnPx cell line were induced to efficiently kill CD70 transfected CHO cells with the CD70xCD3 (I2C) bispecific antibody constructs of the invention. The antibody constructs in this assay were presented using sub-picomolar EC50 values, confirming that they are highly active in the macaque system.

Table 13

EC50 [pM] values of bispecific CD70xCD3 antibody constructs analyzed in a 48-hour FACS-based assay using the 4119LnPx macaque T cell line as effector cells and CHO cells transfected with macaque CD70 as target cells

Bispecific constructs of CD70XCD3 antibodies EC50 [nM] CD70-13D_CCxI2C-scFc 0.07 CD70-16D_CCxI2C-scFc 0.03 CD70-21D_CCxI2C-scFc 0.03 CD70-24D_CCxI2C-scFc 0.14 CD70-25D_CCxI2C-scFc 0.03 CD70_l-G2D_CCxI2C-scFc 0.03 CD70-27D_CCxI2C-scFc 0.12 CD70-28D_CCxI2C-scFc 0.08 CD70-31D_CCxI2C-scFc 0.23 CD70-32D_CCxI2C-scFc 0.03 CD70-42D_CCxI2C-scFc 0.05 CD70-43D_CCxI2C-scFc 0.07 CD70-48D_CCxI2C-scFc 0.04 CD70-62D_CCxI2C-scFc 0.04 CD70-13D_CCxI2C-scFc 0.06

Example 9

Monomer-dimer conversion after (i) three freeze/thaw cycles and (ii) 7 days incubation at 250 μg/ml.

The CD70xCD3 bispecific antibody monomeric construct was subjected to various stress conditions followed by high throughput SEC to determine the percentage of the originally monomeric antibody construct that was converted to a dimeric antibody construct.

(i) 25 μg of monomeric antibody construct was adjusted to a concentration of 250 μg/ml with total formulation buffer and then frozen at -80° C. for 30 minutes followed by thawing for 30 minutes at room temperature. After three freeze/thaw cycles, the dimer content was determined using HP-SEC.

(ii) 25 μg of the monomeric antibody construct was adjusted to a concentration of 250 μg/ml with total formulation buffer, followed by incubation at 37° C. for 7 days. The content of the dimer was determined using HP-SEC.

A high resolution SEC TSK Gel G3000 SWXL column (Tosoh, Tokyo, Japan) was connected to an Akta Purifier 10 FPLC (GE Lifesciences) equipped with an A905 Autosampler. Equilibration buffer and running buffer consisted of 100 mM KH2PO4-200 mM Na ₂ SO ₄ adjusted to pH 6.6. The antibody solution (25 μg of protein) is applied to a balanced column and the elution is carried out at a flow rate of 0.75 ml/min at a maximum pressure of 7 MPa. The entire run was monitored at optical absorbances of 280, 254 and 210 nm. The analysis was performed by peak integration of the 210 nm signal recorded in the Akta Unicorn software evaluation sheet. The dimer content was calculated by dividing the dimer peak area by the total monomer area plus the dimer peak.

The results are presented in Table 14 for a representative number of antibody constructs in

- 69 041992 scFc format. The CD70xCD3 (I2C) bispecific antibody constructs of the invention are presented with <1.5% dimer content (with most constructs <1.0% dimer score) after three freeze/thaw cycles and <0.6% dimer content (with most constructs with a dimer index of 0%) after 7 days of incubation at 37°C.

Table 14

Percentage of Monomeric and Dimeric Bispecific CD70xCD3 Antibody Constructs Detected by High Performance Size Exclusion Chromatography (HP-SEC)

Bispecific Percent dimer after Percent dimer after three antibody constructs 7 days of incubation freezing cycles/ CD70xCD3 at 37°C defrosting CD70-13D_CCxI2C-scFc 0.1 0.4 CD70-16D_CCxI2C-scFc 0.0 0.0 CD70-21D_CCxI2C-scFc 0.0 0.2 CD70-24D_CCxI2C-scFc 0.3 1.1 CD70-25D_CCxI2C-scFc 0.3 0.2 CD70_l-G2D_CCxI2C-scFc 0.0 0.4 CD70-27D_CCxI2C-scFc 0.0 1.5 CD70-28D_CCxI2C-scFc 0.3 0.1 CD70-31D_CCxI2C-scFc 0.0 1.5 CD70-32D_CCxI2C-scFc 0.0 0.8 CD70-42D_CCxI2C-scFc 0.0 0.3 CD70-43D_CCxI2C-scFc 0.0 0.4 CD70-48D_CCxI2C-scFc 0.6 0.5 CD70-62D_CCxI2C-scFc 0.0 0.8 CD70-13D CCxI2C-scFc 0.0 0.7 —

Example 10

Thermal stability.

The antibody aggregation temperature was determined as follows: 40 μl of the antibody design solution at 250 μg/ml was transferred into a disposable cuvette and placed in a Wyatt DynaPro Nanostar dynamic light scattering device (Wyatt). The sample was heated from 40 to 70° C. at a heating rate of 0.5° C./min, continuously obtaining a measured radius. An increase in radius indicating protein melting and aggregation was used by the software package supplied with the DLS device to calculate the aggregation temperature of the antibody construct.

All tested CD70xCD3 (I2C) antibody constructs of the invention exhibited thermal stability with aggregation temperatures >52.0°C shown in Table 1. 15 below for a representative number of antibody constructs in scFc format.

- 70 041992

Table 15

Thermal Stability of Bispecific CD70xCD3 Antibody Constructs as Determined by DLS (Dynamic Light Scattering)

Bispecific constructs of CD70XCD3 antibodies Thermal stability (aggregation DLS °C) CD70-13D_CCxI2C-scFc 52.4 CD70-16D_CCxI2C-scFc 57.7 CD70-21D_CCxI2C-scFc 57.3 CD70-24D_CCxI2C-scFc 57.4 CD70-25D_CCxI2C-scFc 57.6 CD70_l-G2D_CCxI2C-scFc 57.7 CD70-27D_CCxI2C-scFc 57.5 CD70-28D_CCxI2C-scFc 57.5 CD70-31D_CCxI2C-scFc 56.4 CD70-32D_CCxI2C-scFc 57.7 CD70-42D_CCxI2C-scFc 57.6 CD70-43D_CCxI2C-scFc 57.2 CD70-48D_CCxI2C-scFc 56.7 CD70-62D_CCxI2C-scFc 55.5 CD70-13D_CCxI2C-scFc 57.7

Example 11.

Stability after 24 h incubation in human plasma.

Purified bispecific antibody constructs were incubated in a 1:5 ratio in human plasma pool at 37°C for 96 h at a final concentration of 2-20 μg/mL. Following plasma incubation, antibody constructs were compared in a 51-chromium release assay with stimulated human CD8+ enriched T cells and CHO cells transfected with human CD70 at an initial concentration of 0.01-0.1 μg/mL and with an effector cell:target cell ratio (E:T) 10:1 (assay as described in Example 8.1). Unincubated, freshly thawed bispecific antibody constructs were included as controls.

The results are presented in table. 16 for a representative number of scFc antibody constructs. Most of the antibody constructs tested had very satisfactory plasma stability (EC ₅₀ in plasma/EC ₅₀ control) <3.0 or <2.5.

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Table 16

EC50 values of CD70xCD3 antibody constructs (I2C) with and without plasma incubation and calculated plasma/control values

Plasma to Bispecific _ec50 [pM] control antibody constructs with plasma C 5ez plasma (EC ₅₀ Plasma/EC ₅₀ CD70xCD3 control) CD70-13D_CCxI2C-scFc 0.06 0.07 0.8 CD70-16D_CCxI2C-scFc 0.01 0.005 18 CD70-21D_CCxI2C-scFc 0.05 0.06 0.9 CD70-24D_CCxI2C-scFc n/a 0.15 n/a CD70-25D_CCxI2C-scFc 0.00 0.01 0.2 CD70_l-G2D_CCxI2C-scFc 0.07 0.01 6, 8 CD70-27D_CCxI2C-scFc 0.08 0.08 eleven CD70-28D_CCxI2C-scFc 0.01 0.03 0.5 CD70-31D_CCxI2C-scFc 0.18 0.11 16 CD70-32D_CCxI2C-scFc 0.03 0.08 0.4 CD70-42D_CCxI2C-scFc 0.07 0.05 14 CD70-43D_CCxI2C-scFc 0.11 0.08 14 CD70-48D_CCxI2C-scFc 0.03 0.01 thirty CD70-62D_CCxI2C-scFc 0.05 0.02 2.2 CD70-13D CCxI2C-scFc 0.02 0.05 0.3 —

Example 12.

Turbidity at an antibody concentration of 2500 µg/mL.

ml of a solution of the purified antibody construct at a concentration of 250 μg/ml was concentrated using rotary concentrators to 2500 μg/ml. After 16 hours storage at 5° C., the turbidity of the antibody solution was determined by optical absorbance OD340 nm against formulation buffer.

The results are presented in Table 17 for a representative number of CD70xCD3 (I2C) antibody constructs in scFc format. All antibody constructs tested had a very satisfactory turbidity of < 0.05.

Table 17

Turbidity of antibody constructs after concentration to 2.5 mg/mL overnight

Bispecific constructs of CD70xCD3 antibodies Turbidity at 2500 µg/mL [OD340] CD70-13D_CCxI2C-scFc 0.023 CD70-16D_CCxI2C-scFc 0.017 CD70-21D_CCxI2C-scFc 0.015 CD70-24D_CCxI2C-scFc 0.019 CD70-25D_CCxI2C-scFc 0.027 CD70_l-G2D_CCxI2C-scFc 0.022 CD70-27D_CCxI2C-scFc 0.034 CD70-28D_CCxI2C-scFc 0.011 CD70-31D_CCxI2C-scFc 0.015 CD70-32D_CCxI2C-scFc 0.024 CD70-42D_CCxI2C-scFc 0.019 CD70-43D_CCxI2C-scFc 0.023 CD70-48D_CCxI2C-scFc 0.023 CD70-62D_CCxI2C-scFc 0.031 CD70-13D_CCxI2C-scFc 0.017

- 72 041992

Example 13

Protein homogeneity by high performance cation exchange chromatography.

Protein homogeneity of the antibody constructs of the invention was analyzed by high performance cation exchange chromatography CIEX.

μg of the monomeric antibody construct was diluted with 50 ml of binding buffer A (20 mM sodium dihydrogen phosphate, 30 mM NaCl, 0.01% sodium octanate, pH 5.5) and 40 ml of this solution was applied to a 1 ml BioPro SP-F column (YMC, Germany ) connected to an Akta Micro FPLC device (GE Healthcare, Germany). After binding to the sample, a washing step was performed with additional binding buffer. Buffer B was used to elute the protein with a linear gradient of salt (20 mM sodium dihydrogen phosphate, 1000 mM NaCl, 0.01% sodium octanate, pH 5.5) until 50% buffer B was applied over 10 column volumes. The entire run was monitored at optical absorbances of 280, 254 and 210 nm. The analysis was performed by peak integration of the 280 nm signal recorded in the Akta Unicorn software evaluation sheet.

The results are presented in table. 18 for a representative number of CD70xCD3 (I2C) antibody constructs in scFc format. All antibody constructs tested had satisfactory >60% homogeneity (area under the curve (=AUC) of the main peak), nine of the 15 constructs had >70% homogeneity.

Table 18

Protein homogeneity of antibody constructs (% AUC of the main peak)

Bispecific constructs of CD70XCD3 antibodies Protein homogeneity % AUC of the main peak CD70-13D_CCxI2C-scFc 81 CD70-16D_CCxI2C-scFc 79 CD70-21D_CCxI2C-scFc 74 CD70-24D_CCxI2C-scFc 73 CD70-25D_CCxI2C-scFc 71 CD70_l-G2D_CCxI2C-scFc 69 CD70-27D_CCxI2C-scFc 70 CD70-28D_CCxI2C-scFc 67 CD70-31D_CCxI2C-scFc 68 CD70-32D_CCxI2C-scFc 76 CD70-42D_CCxI2C-scFc 67 CD70-43D_CCxI2C-scFc 62 CD70-48D_CCxI2C-scFc 70 CD70-62D_CCxI2C-scFc 66 CD70-13D_CCxI2C-scFc 73

Example 14

Surface hydrophobicity measured with HIC Butyl.

The surface hydrophobicity of the bispecific antibody constructs of the invention was tested in HIC hydrophobic interactive chromatography in flow mode.

µg of monomeric antibody construct was diluted with total formulation buffer to a final volume of 500 µl (10 mM citric acid, 75 mM lysine HCl, 4% trehalose, pH 7.0) and applied to a 1 ml butyl sepharose FF column (GE Healthcare, Germany) connected to the FPLC Akta Purifier system (GE Healthcare, Germany). The entire run was monitored at optical absorbances of 280, 254 and 210 nm. The analysis was performed by peak integration of the 280 nm signal recorded in the Akta Unicorn software evaluation sheet. The elution behavior was assessed by comparing the area and rate of rise and fall of the protein signal, thereby indicating the strength of the BiTE albumin fusion interaction with the matrix.

A representative number of CD70xCD3 (I2C) scFc antibody constructs were analyzed and shown to have good elution that was generally fast and complete.

Example 15

Gap in specific activity between monomeric and dimeric isoform of bispecific

- 73 041992 antibody designs.

To determine the difference in cytotoxic activity between the monomeric and dimeric isoform of the individual CD70xCD3 bispecific antibody constructs (referred to as the specific activity gap), an 18 hour cytotoxicity assay was performed releasing 51-chromium as described above (Example 8.1), the monomer and dimer of the purified bispecific construct antibodies. The effector cells were stimulated human CD8+ enriched T cells. Target cells were CHO cells transfected with human CD70. The ratio of effector cell:target cell (E:T) was 10:1. The specific activity gap was calculated as the ratio between the EC50 values.

The results are presented in table. 19 for a representative number of scFc antibody constructs. The specific activity gaps of the studied CD70xCD3 (I2C) bispecific antibody constructs ranged between 0.0 and 1.5. Therefore, there is no substantially more active dimer than its corresponding monomer.

Table 19

Gap of specific activity between monomeric and dimeric isoform

Bispecific constructs of CD70xCD3 antibodies EC ₅₀ [ΓΊΜ] monomer EC ₅₀ [ΓΊΜ] dimer Ratio EC ₅₀ monomer/EC ₅₀ dimer CD70-13D_CCxI2C-scFc 0.07 0.11 0.6 CD70-16D_CCxI2C-scFc 0.005 0.07 oh 1 CD70-21D_CCxI2C-scFc 0.06 0.04 1.5 CD70-24D_CCxI2C-scFc 0.15 0.24 0.6 CD70-25D_CCxI2C-scFc 0.01 0.09 0, 1 CD70_l-G2D_CCxI2C-scFc 0.01 0.06 0.2 CD70-27D_CCxI2C-scFc 0.08 0.25 0.3 CD70-28D_CCxI2C-scFc 0.03 0.09 0.3 CD70-31D_CCxI2C-scFc 0.11 0.24 0.5 CD70-32D_CCxI2C-scFc 0.08 0.23 0.3 CD70-42D_CCxI2C-scFc 0.05 70 0, 0 CD70-43D_CCxI2C-scFc 0.08 0.20 0.4 CD70-48D_CCxI2C-scFc 0.01 0.09 0, 1 CD70-62D_CCxI2C-scFc 0.02 0.17 0, 1 CD70-13D_CCxI2C-scFc 0.05 0.12 0.4

Example 16

CD27 does not inhibit the binding of anti-CD70 scFv molecules.

This assay was performed to test whether a soluble form of CD27 (136-458 pg/ml soluble CD27 in human serum, Huang J. et al. (2013) J Immunol 190: 1-9) would interfere with the binding domains of an anti-CD70 antibody of the invention with CD70.

To test the binding of human CD27 to CHO cells transfected with human CD70, the cells were incubated with human CD27 for 30 min at 4°C (1 μg/ml, R&D no. 382-CD-100). Bound CD27 was detected with an anti-HIS antibody (5 μg/ml, AbD Serotec) followed by an anti-mouse Fc-gamma-PE IgG antibody (1:100; Jackson Immunoresearch #115-116071). As a negative control, cells were incubated with PBS/2% FCS instead of CD27.

To test for substitution of anti-CD70 scFv for CD27, CHO cells transfected with human CD70 were incubated with or without CD27 for 30 min at 4°C (1 μg/ml, R&D no. 382-CD-100). Cells were then washed twice and then stained with crude, undiluted periplasmic extract containing CD70-binding scFv. Bound scFvs were detected with mouse anti-FLAG M2 monoclonal antibody (1 μg/ml, Sigma F1804) followed by anti-mouse IgG Fc-gamma-PE (1:100; Jackson Immunoresearch no. 115-116-071). As a negative control, cells were incubated with non-specific scFv instead of anti-CD70 scFv. CD27 and all antibodies were diluted in PBS/2% FCS.

No competition between soluble CD27 and anti-CD70 scFv was observed for any of the CD70 binding domains of the invention that were analyzed.

- 74 041992

Table 20

Sequence listing

SEQ ID NO: CD70 epito R Designation Format/ Source Amino acid sequence 1 CD70-1 VH CDR1 TYGMH 2 CD70-1 VH CDR2 VIWYDGSNKYYGDSVKG 3 CD70-1 VH CDR3 DNSHYYYGMDV 4 CD70-1 VL CDR1 TGSSSNIGAGYDVN 5 CD70-1 VL CDR2 VNNNRPS 6 CD70-1 VL CDR3 QSYDTSLSASV 7 CD70-1 vh QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGKGLEWVAVIWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSS 8 CD70-1 VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAGYDVNWYQQFPGTAPKLLIYVNNNR PSGVPDRFSGSTSGTSASLAITGLQAED EADYYCQSYDTSLSASVFGGGTRLTVL 9 III CD70-1 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGGGTRLTVLS 10 CD70-1 bispecific molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED

- 75 041992

EAEYYCVLWYSNRWVFGGGTKLTVL eleven CD70-2 VH CDR1 SYGMH 12 CD70-2 VH CDR2 VIWYDGSDKYFADSVKG 13 CD70-2 VH CDR3 DGIAGARYVYFDY 14 CD70-2 VL CDR1 RASQGISNYLA 15 CD70-2 VL CDR2 AASSLQG 16 CD70-2 VL CDR3 QQYYNYPFT 17 CD70-2 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVIWYDGS DKYFADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDGIAGARYVYFDYW GQGTLVTVSS 18 CD70-2 VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWFQQKPGKAPKSLIYAASSLQG GVPSKFSGSGSGTDFTLTISSLQPEDFA TYYCQQYYNYPFTFGPGTTVDIK 19 II CD70-2 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVIWYDGS DKYFADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDGIAGARYVYFDYW GQGTLVTVSSGGGGSGGGGSGGGGSDIQ MTQSPSSLSASVGDRVTITCRASQGISN YLAWFQQKPGKAPKSLIYAASSLQGGVP SKFSGSGSGTDFTLTISSLQPEDFATYY CQQYYNYPFTFGPGTTVDIK 20 CD70-2 bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVIWYDGS DKYFADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDGIAGARYVYFDYW GQGTLVTVSSGGGGSGGGGSGGGGSDIQ MTQSPSSLSASVGDRVTITCRASQGISN YLAWFQQKPGKAPKSLIYAASSLQGGVP SKFSGSGSGTDFTLTISSLQPEDFATYY CQQYYNYPFTFGPGTTVDIKSGGGGSEV QLVESGGGLVQPGGSLKLSCAASGFTFN

- 76 041992

KYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAY WGQGTLVTVSSGGGGSGGGGSGGGGSQT WTQEPSLTVSPGGTVTLTCGSSTGAVT S GNYPNWVQQKPGQAPRGLIGGTKFLAP GTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 21 CD70-3 VH CDR1 SYGMH 22 CD70-3 VH CDR2 VTWYDGSNKYYGDSVKG 23 CD70-3 VH CDR3 DLLRGVKGYAMDV 24 CD70-3 VL CDR1 RASQSLRRIYLA 25 CD70-3 VL CDR2 DVFDRAT 26 CD70-3 VL CDR3 QQYSDSPFT 27 CD70-3 vh QEQLVESGGGWQPGRSLRLSCAASGFT FSSYGMHWVRQAPGKGLEWVAVTWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSS 28 CD70-3 VL EIVLTQSPGTLSLSPGERATLSCRASQS LRRIYLAWYQQKPGQAPRLLIYDVFDRA TGIPDRSGGGSGTDFTLTISRLEPEDF AVYYCQQYSDSPFTFGPGTKVDIK 29 IIIv CD70-3 scFv QEQLVESGGGWQPGRSLRLSCAASGFT FSSYGMHWVRQAPGKGLEWVAVTWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSDSPFTFGPGTKVDIK thirty CD70-3 bispecificity molecular molecule QEQLVESGGGWQPGRSLRLSCAASGFT FSSYGMHWVRQAPGKGLEWVAVTWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN

- 77 041992

SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSDSPFTFGPGTKVDIKSGGGGSE VQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNN YATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTKLTVL 31 CD70-4 VH CDR1 SYGIS 32 CD70-4 VH CDR2 WISAYNGYTHYAQKLQG 33 CD70-4 VH CDR3 DYGGNDYYGMDV 34 CD70-4 VL CDR1 SGSSSNIGINYVY 35 CD70-4 VL CDR2 RSDQRPS 36 CD70-4 VL CDR3 AAWDDSLSGW 37 CD70-4 vh QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYNG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSS 38 CD70-4 VL QSVLTQPPSASGTPGQRVTISCSGSSSN IGINYVYWYQQLPGTAPKLLIYRSDQRP SGVPDRFSGSKSGTSASLALSGLRSEDE ADYYCAAWDDSLSGWFGGGTKLTVL 39 I CD70-4 scFv QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYNG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGGSGGGGSQSVL

- 78 041992

TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAWDDSLSGWFGGGTKLTVL 40 CD70-4 bispecific molecule QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYNG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAWDDSLSGWFGGGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 41 CD70-5 VH CDR1 SGGYYWS 42 CD70-5 VH CDR2 YIFYSGSTDYNPSLKS 43 CD70-5 VH CDR3 SGYSYALFDH 44 CD70-5 VL CDR1 RASQFIGRYFN 45 CD70-5 VL CDR2 AESSLQS 46 CD70-5 VL CDR3 QQSYSTPWT 47 CD70-5 vh QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKGLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSS 48 CD70-5 VL DIQMTQSPSSLSASVGDRVTISCRASQF IGRYFNWYQQQPGKAPKVLIYAESSLQS

- 79 041992

GVPSRFSGSGSGTEFTLTISSLQPEDFA RYYCQQSYSTPWTFGQGTKVEIK 49 VIII CD70-5 scFv QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKGLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQQPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFARYYCQ QSYSTPWTFGQGTKVEIK 50 CD70-5 bispecificity molecular molecule QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKGLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQQPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFARYYCQ QSYSTPWTFGQGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 51 CD70-6 VH CDR1 SGGYYWS 52 CD70-6 VH CDR2 YIFYSGSTDYNPSLKS 53 CD70-6 VH CDR3 SGYSYALFDH 54 CD70-6 VL CDR1 RASQFIGRYFN 55 CD70-6 VL CDR2 AESSLQS 56 CD70-6 VL CDR3 QQSYSTPFT

- 80 041992

57 CD70-6 vh QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSS 58 CD70-6 VL DIQMTQSPSSLSASVGDRVTISCRASQF IGRYFNWYQQQPGKAPKVLIYAESSLQS GVPSRFSGSGSGTEFTLTISSLQPEDFA 59 VIII CD70-6 scFv QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQQPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFARYYCQ QSYSTPFTFGCGTKVEIK 60 CD70-6 bispecificity molecular molecule QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQQPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFARYYCQ QSYSTPFTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY

- 81 041992

YCVLWYSNRWVFGGGTKLTVL 61 CD70-7 VH CDR1 SYYLH 62 CD70-7 VH CDR2 IVDPSGGSTSYDQKFQG 63 CD70-7 VH CDR3 DYGDYVFDY 64 CD70-7 VL CDR1 SGSSSNIGTNTVN 65 CD70-7 VL CDR2 INNQRPS 66 CD70-7 VL CDR3 ATWDDSLNGPV 67 CD70-7 vh QVHLVQSGAEVKKPGASVRVSCKASGYT FTSYYLHWVRQAPGQCLEWMGIVDPSGG STSYDQKFQGRFTMTRDTSTSTVYMELS SLRSEDTAVYYCARDYGDYVFDYWGQGT LVTVSS 68 CD70-7 VL QSVLTQPPSASGTPGQRVTISCSGSSSN IGTNTVNWYQQLPGTAPQLLIYINNQRP SGVPDRFSGSKSGTSASLAISGLQSEDE ADYYCATWDDSLNGPWGCGTKLTVL 69 I CD70-7 scFv QVHLVQSGAEVKKPGASVRVSCKASGYT FTSYYLHWVRQAPGQCLEWMGIVDPSGG STSYDQKFQGRFTMTRDTSTSTVYMELS SLRSEDTAVYYCARDYGDYVFDYWGQGT LVTVSSGGGGSGGGGSGGGGSQSVLTQP PSASGTPGQRVTISCSGSSSNIGTNTVN WYQQLPGTAPQLLIYINNQRPSGVPDRF SGSKSGTSASLAISGLQSEDEADYYCAT WDDSLNGPWGCGTKLTVL 70 CD70-7 bispecificity chesky molecule QVHLVQSGAEVKKPGASVRVSCKASGYT FTSYYLHWVRQAPGQCLEWMGIVDPSGG STSYDQKFQGRFTMTRDTSTSTVYMELS SLRSEDTAVYYCARDYGDYVFDYWGQGT LVTVSSGGGGSGGGGSGGGGSQSVLTQP PSASGTPGQRVTISCSGSSSNIGTNTVN WYQQLPGTAPQLLIYINNQRPSGVPDRF SGSKSGTSASLAISGLQSEDEADYYCAT WDDSLNGPWGCGTKLTVLSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 82 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 71 CD70-8 VH CDR1 SYGMH 72 CD70-8 VH CDR2 VIWYDGSDKYFADSVKG 73 CD70-8 VH CDR3 DGIAGARYVYFDY 74 CD70-8 VL CDR1 RASQGISNYLA 75 CD70-8 VL CDR2 AASSLQG 76 CD70-8 VL CDR3 QQYYNYPFT 77 CD70-8 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVIWYDGS DKYFADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDGIAGARYVYFDYW GQGTLVTVSS 78 CD70-8 VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWFQQKPGKAPKSLIYAASSLQG GVPSKFSGSGSGTDFTLTISSLQPEDFA TYYCQQYYNYPFTFGCGTTVDIK 79 II CD70-8 scFv QVQLVE S GGGWQPGRS LRL S CAAS G FT FSSYGMHWVRQAPGKCLEWVAVIWYDGS DKYFADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDGIAGARYVYFDYW GQGTLVTVSSGGGGSGGGGSGGGGSDIQ MTQSPSSLSASVGDRVTITCRASQGISN YLAWFQQKPGKAPKSLIYAASSLQGGVP SKFSGSGSGTDFTLTISSLQPEDFATYY CQQYYNYPFTFGCGTTVDIK 80 CD70-8 bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FT FSSYGMHWVRQAPGKCLEWVAVIWYDGS DKYFADSVKGRFTISRDNSKNTLYLQMN

- 83 041992

SLRAEDTAVYYCARDGIAGARYVYFDYW GQGTLVTVSSGGGGSGGGGSGGGGSDIQ MTQSPSSLSASVGDRVTITCRASQGISN YLAWFQQKPGKAPKSLIYAASSLQGGVP SKFSGSGSGTDFTLTISSLQPEDFATYY CQQYYNYPFTFGCGTTVDIKSGGGGSEV QLVESGGGLVQPGGSLKLSCAASGFTFN KYAMNWVRQAPGKGLEWVARIRSKYNNY ATYYADSVKDRFTISRDDSKNTAYLQMN NLKTEDTAVYYCVRHGNFGNSYISYWAY WGQGTLVTVSSGGGGSGGGGSGGGGSQT WTQEPSLTVSPGGTVTLTCGSSTGAVT S GNYPNWVQQKPGQAPRGLIGGTKFLAP GTPARFSGSLLGGKAALTLSGVQPEDEA EYYCVLWYSNRWVFGGGTKLTVL 81 CD70-9 VH CDR1 SYGIS 82 CD70-9 VH CDR2 WISAYNGYTHYAQKLQG 83 CD70-9 VH CDR3 DYGGNDYYGMDV 84 CD70-9 VL CDR1 SGSSSNIGINYVY 85 CD70-9 VL CDR2 RSDQRPS 86 CD70-9 VL CDR3 AAWDDSLSGW 87 CD70-9 vh QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYNG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSS 88 CD70-9 VL QSVLTQPPSASGTPGQRVTISCSGSSSN IGINYVYWYQQLPGTAPKLLIYRSDQRP SGVPDRFSGSKSGTSASLALSGLRSEDE ADYYCAAWDDSLSGWFGGGTKLTVL 89 I CD70-9 scFv QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYNG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGGSGGGGSQSVL

- 84 041992

TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAWDDSLSGWFGCGTKLTVL 90 CD70-9 bispecific molecule QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQCLEWMGWISAYNG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAWDDSLSGWFGCGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 91 CD70-10 VH CDR1 SGGYYWS 92 CD70-10 VH CDR2 YIFYSGSTDYNPSLKS 93 CD70-10 VH CDR3 SGYSYALFDH 94 CD70-10 VL CDR1 RASQFIGRYFN 95 CD70-10 VL CDR2 AESSLQS 96 CD70-10 VL CDR3 QQSYSTPWT 97 CD70-10 vh QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSS 98 CD70-10 VL DIQMTQSPSSLSASVGDRVTISCRASQF IGRYFNWYQQQPGKAPKVLIYAESSLQS

- 85 041992

GVPSRFSGSGSGTEFTLTISSLQPEDFA RYYCQQSYSTPWTFGCGTKVEIK 99 VIII CD70-10 scFv QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQQPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFARYYCQ QSYSTPWTFGCGTKVEIK 100 CD70-10 bispecificity molecular molecule QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQHPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDHWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQQPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFARYYCQ QSYSTPWTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 101 CD70-11 VH CDR1 TYGMH 102 CD70-11 VH CDR2 VIWYDGSNKYYGDSVKG 103 CD70-11 VH CDR3 DNSHYYYGMDV 104 CD70-11 VL CDR1 TGSSSNIGAGYDVN 105 CD70-11 VL CDR2 VNNNRPS 106 CD70-11 VL CDR3 QSYETSLASV

- 86 041992

107 CD70-11 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSS 108 CD70-11 VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAGYDVNWYQQFPGTAPKLLIYVNNNR PSGVPDRFSGSTSGTSASLAITGLQAED EADYYCQSYETSLSASVFGCGTRLTVL 109 III CD70-11 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGCGTRLTVL 110 CD70-11 bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGKCLEWVAVIWYDGS NKYYGDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED

- 87 041992

EAEYYCVLWYSNRWVFGGGTKLTVL 111 CD70-12 VH CDR1 YYGMH 112 CD70-12 VH CDR2 VIWYDGSNKYYADSVKG 113 CD70-12 VH CDR3 DREMGSRGDFDY 114 CD70-12 VL CDR1 RASQGINNYLA 115 CD70-12 VL CDR2 AVSILQS 116 CD70-12 VL CDR3 QQYNFYPFS 117 CD70-12 vh QAQLVE S GGGWQPGRS LRL S CAAS G FT FSYYGMHWVRQAPGKCLEWVAVIWYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSS 118 CD70-12 VL DIQMTQSPSSLSASVGDRVTITCRASQG INNYLAWFQQKPGKAPKSLIYAVSILQS GVPSKFSGSGSGTDFTLTIGNLQPEDFA TYYCQQYNFYPFSFGCGTKVDIK 119 V CD70-12 scFv QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKCLEWVAVIWYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTIGNLQPEDFATYYC QQYNFYPFSFGCGTKVDIK 120 CD70-12 bispecificity molecular molecule QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKCLEWVAVIWYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTIGNLQPEDFATYYC QQYNFYPFSFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 88 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 121 CD70-13 VH CDR1 SYAMS 122 CD70-13 VH CDR2 VISGSGGRPNYADSVKG 123 CD70-13 VH CDR3 VDYSNYLFFDY 124 CD70-13 VL CDR1 RAGQSVRSSYLG 125 CD70-13 VL CDR2 GASS RAT 126 CD70-13 VL CDR3 QQYGYSPPT 127 CD70-13 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSS 128 CD70-13 VL EIVLTQSPGTLSLSPGEGATLSCRAGQS VRSSYLGWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPPTFGGGTKLEIK 129 I CD70-13 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIK 130 CD70-13 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN

- 89 041992

SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 131 CD70-14 VH CDR1 I YAMS 132 CD70-14 VH CDR2 AISGSGGSTFYADSVKG 133 CD70-14 VH CDR3 HDYSNYPYFDY 134 CD70-14 VL CDR1 RASQSVRSSYLA 135 CD70-14 VL CDR2 GASS RAT 136 CD70-14 VL CDR3 QQYGDLPFT 137 CD70-14 vh EVQLLESGGGLVQPGGSLKLSCAASGFT ESIYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 138 CD70-14 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKLEIK 139 II CD70-14 scFv EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT

- 90 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIK 140 CD70-14 bispecific molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 141 CD70-15 VH CDR1 SYAMS 142 CD70-15 VH CDR2 AISGSGGRTFYADSVEG 143 CD70-15 VH CDR3 HDYSNYPYFDY 144 CD70-15 VL CDR1 RASQSVRSSYLA 145 CD70-15 VL CDR2 GASS RAT 146 CD70-15 VL CDR3 QQYGSSPFT 147 CD70-15 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 148 CD70-15 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA

- 91 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKLEIK 149 II CD70-15 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIK 150 CD70-15 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 151 CD70-16 VH CDR1 SYAMS 152 CD70-16 VH CDR2 AISGSGGRTFYADSVEG 153 CD70-16 VH CDR3 HDYSNYPYFDY 154 CD70-16 VL CDR1 RASQSIRSSYLA 155 CD70-16 VL CDR2 GASS RAT 156 CD70-16 VL CDR3 QQYGDLPFT

- 92 041992

157 CD70-16 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 158 CD70-16 VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSSYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKLEIK 159 II CD70-16 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIK 160 CD70-16 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 93 041992

YYCVLWYSNRWVFGGGTKLTVL 161 CD70-17 VH CDR1 SYAMS 162 CD70-17 VH CDR2 AISGSGGRTHYADSVKG 163 CD70-17 VH CDR3 HDYSNYPYFDY 164 CD70-17 VL CDR1 RASQSVRSSYLA 165 CD70-17 VL CDR2 GASS RAT 166 CD70-17 VL CDR3 QQYGSSPFT 167 CD70-17 vh EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 168 CD70-17 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKLEIK 169 II CD70-17 scFv EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIK 170 CD70-17 bispecificity chesky molecule EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 94 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 171 CD70-18 VH CDR1 SYAMS 172 CD70-18 VH CDR2 LISGSGGRTHYADSVKG 173 CD70-18 VH CDR3 HDYSNYPYFDY 174 CD70-18 VL CDR1 RASQSVRSTYLA 175 CD70-18 VL CDR2 DASS RAT 176 CD70-18 VL CDR3 QQYGSSPPT 177 CD70-18 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 178 CD70-18 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYDAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTFGGGTKLEIK 179 II CD70-18 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTKLEIK 180 CD70-18 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN

- 95 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 181 CD70-19 VH CDR1 TYAMS 182 CD70-19 VH CDR2 AISGSGGSTFYADSVKG 183 CD70-19 VH CDR3 HDYSNYPYFDY 184 CD70-19 VL CDR1 RASQSVRSSYLA 185 CD70-19 VL CDR2 GASS RAT 186 CD70-19 VL CDR3 QQYGDLPFT 187 CD70-19 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 188 CD70-19 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKLEIK 189 VI CD70-19 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 96 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIK 190 CD70-19 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 191 CD70-20 VH CDR1 TYAMS 192 CD70-20 VH CDR2 LISGSGGRTYYADSVKG 193 CD70-20 VH CDR3 HDYSNYPYFDY 194 CD70-20 VL CDR1 RASQGVRSDYLA 195 CD70-20 VL CDR2 GASS RAT 196 CD70-20 VL CDR3 QQYGSTPPT 197 CD70-20 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 198 CD70-20 VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSDYLAWYQQKPGQALRLLIYGASSRA

- 97 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYHCQQYGSTPPTFGGGTKLEIK 199 II CD70-20 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQALRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKLEIK 200 CD70-20 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQALRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 201 CD70-21 VH CDR1 TYAMS 202 CD70-21 VH CDR2 AISGSGGRTFYADSVEG 203 CD70-21 VH CDR3 HDYSNYPYFDY 204 CD70-21 VL CDR1 RASQSVRSTYLA 205 CD70-21 VL CDR2 GASS RAT 206 CD70-21 VL CDR3 QQYGDLPFT

- 98 041992

207 CD70-21 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 208 CD70-21 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGPGTKLEIK 209 VI CD70-21 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIK 210 CD70-21 bispecificity chesky molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 99 041992

YYCVLWYSNRWVFGGGTKLTVL 211 CD70-22 VH CDR1 SYAMS 212 CD70-22 VH CDR2 AISGSGGYTYYADSVKG 213 CD70-22 VH CDR3 HDYSNYPYFDY 214 CD70-22 VL CDR1 RASQSVRSNYLA 215 CD70-22 VL CDR2 GASS RAT 216 CD70-22 VL CDR3 QQYGDLPFT 217 CD70-22 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 218 CD70-22 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 219 VI CD70-22 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 220 CD70-22 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 100 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 221 CD70-23 VH CDR1 VYAMS 222 CD70-23 VH CDR2 TISDSGGSTFYADSVKG 223 CD70-23 VH CDR3 HDYSNYAYFDY 224 CD70-23 VL CDR1 RASQSVRSSYLA 225 CD70-23 VL CDR2 GASS RAT 226 CD70-23 VL CDR3 QQYGDLPFT 227 CD70-23 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSS 228 CD70-23 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 229 VI CD70-23 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 230 CD70-23 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN

- 101 041992

RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 231 CD70-24 VH CDR1 SYAMS 232 CD70-24 VH CDR2 AISGSGGSTFYADSVKG 233 CD70-24 VH CDR3 HDYSNYPYFDY 234 CD70-24 VL CDR1 RASQSVRSSYLA 235 CD70-24 VL CDR2 GASS RAT 236 CD70-24 VL CDR3 QQYGDLPFT 237 CD70-24 vh EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSS 238 CD70-24 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 239 VI CD70-24 scFv EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 102 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 240 CD70-24 bispecific molecule EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 241 CD70-25 VH CDR1 SYAMS 242 CD70-25 VH CDR2 AISGSGGRTFYADSVEG 243 CD70-25 VH CDR3 HDYSNYPYFDY 244 CD70-25 VL CDR1 RASQSVRSNYLA 245 CD70-25 VL CDR2 GASS RAT 246 CD70-25 VL CDR3 QQYGDLPFT 247 CD70-25 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 248 CD70-25 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA

- 103 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 249 VI CD70-25 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 250 CD70-25 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 251 CD70-26 VH CDR1 SYAMS 252 CD70-26 VH CDR2 AISGSGGRTFYADSVEG 253 CD70-26 VH CDR3 HDYSNYPYFDY 254 CD70-26 VL CDR1 RASQSVRSSYLA 255 CD70-26 VL CDR2 GASS RAT 256 CD70-26 VL CDR3 QQYGSSPFT

- 104 041992

257 CD70-26 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 258 CD70-26 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKVEIK 259 II CD70-26 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIK 260 CD70-26 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 105 041992

YYCVLWYSNRWVFGGGTKLTVL 261 CD70-27 VH CDR1 TYAMS 262 CD70-27 VH CDR2 AISGSGGGTFYADSVKG 263 CD70-27 VH CDR3 HDYSNYPYFDY 264 CD70-27 VL CDR1 RASQSIRSNYLA 265 CD70-27 VL CDR2 GASS RAT 266 CD70-27 VL CDR3 QQYGSSPFT 267 CD70-27 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 268 CD70-27 VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKVEIK 269 VI CD70-27 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIK 270 CD70-27 bispecificity chesky molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 106 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 271 CD70-28 VH CDR1 TYAMS 272 CD70-28 VH CDR2 LISGSGGRTYYADSVKG 273 CD70-28 VH CDR3 HDYSNYPYFDY 274 CD70-28 VL CDR1 RASQSVRSNYLA 275 CD70-28 VL CDR2 GASNRAT 276 CD70-28 VL CDR3 QQYGISPPT 277 CD70-28 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 278 CD70-28 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGASNRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGISPPTFGGGTKVEIK 279 II CD70-28 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIK 280 CD70-28 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN

- 107 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 281 CD70-29 VH CDR1 SYAMS 282 CD70-29 VH CDR2 VISGSGGRTHYADSGKG 283 CD70-29 VH CDR3 HDYSNYPYFDY 284 CD70-29 VL CDR1 RASQSVRSSYLA 285 CD70-29 VL CDR2 GASS RAT 286 CD70-29 VL CDR3 EQYGNSPPT 287 CD70-29 vh EVQLLESGGGLVQPGGSLRLSCAASGFN FASYAMSWVRQAPGKGLEWVSVISGSGG RTHYADSGKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 288 CD70-29 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIFGAS SRA TGIPDRFSGSESGTDFTLTINRLEPEDF AVYYCEQYGNSPPTFGGGTKVEIK 289 II CD70-29 scFv EVQLLESGGGLVQPGGSLRLSCAASGFN FASYAMSWVRQAPGKGLEWVSVISGSGG RTHYADSGKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 108 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIFGASSRATGIPD RFSGSESGTDFTLTINRLEPEDFAVYYC EQYGNSPPTFGGGTKVEIK 290 CD70-29 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFN FASYAMSWVRQAPGKGLEWVSVISGSGG RTHYADSGKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIFGASSRATGIPD RFSGSESGTDFTLTINRLEPEDFAVYYC EQYGNSPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 291 CD70-30 VH CDR1 TYAMS 292 CD70-30 VH CDR2 LISGSGGRTYYADSVKG 293 CD70-30 VH CDR3 HDYSNYPYFDY 294 CD70-30 VL CDR1 RASQSVRSSYLA 295 CD70-30 VL CDR2 GASS RAT 296 CD70-30 VL CDR3 QQYGSSPPP 297 CD70-30 vh EVQLLESGGGWQPGRSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 298 CD70-30 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA

- 109 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPPPFGGGTKVEIK 299 II CD70-30 scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPPFGGGTKVEIK 300 CD70-30 bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPPFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 301 CD70-31 VH CDR1 SYAMS 302 CD70-31 VH CDR2 AISGSGGRAQYADSVQG 303 CD70-31 VH CDR3 HDYSNYPYFDY 304 CD70-31 VL CDR1 RASQSVSSNLA 305 CD70-31 VL CDR2 GSSSRAT 306 CD70-31 VL CDR3 QQYGSSPPP

- 110 041992

307 CD70-31 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 308 CD70-31 VL EIVLTQSPATLSVSPGERATLSCRASQS VS SNLAWYQQKPGQAPRLLIYGS S SRAT GIPDRFSGSGSGTDFTLTISRLEPEDFA VYYCQQYGSSPPPFGGGTKVEIK 309 II CD70-31 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIK 310 CD70-31 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY

- 111 041992

YCVLWYSNRWVFGGGTKLTVL 311 CD70-32 VH CDR1 SYAMS 312 CD70-32 VH CDR2 AISGSGGRTFYADSVEG 313 CD70-32 VH CDR3 HDYSNYPYFDY 314 CD70-32 VL CDR1 RASQGVRSDYLA 315 CD70-32 VL CDR2 GASS RAT 316 CD70-32 VL CDR3 QQYGSTPPT 317 CD70-32 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 318 CD70-32 VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSDYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYHCQQYGSTPPTFGGGTKVEIK 319 II CD70-32 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIK 320 CD70-32 bispecific molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 112 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 321 CD70-33 VH CDR1 TYAMS 322 CD70-33 VH CDR2 TISDSGGSTFYADSVMG 323 CD70-33 VH CDR3 HDYSNYAFFDY 324 CD70-33 VL CDR1 RASQSVSSNLA 325 CD70-33 VL CDR2 GASS RAT 326 CD70-33 VL CDR3 QQYYSTPFT 327 CD70-33 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVMGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYAFFDYWGQ GTLVTVSS 328 CD70-33 VL EIVLTQSPATLSVSPGERATLSCRASQS VS SNLAWYQQKPGQAPRLLIYGAS SRAT GIPDRFSGSGSGTDFTLTISSLQAEDVA VYYCQQYYSTPFTFGPGTKVEIK 329 II CD70-33 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVMGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYAFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGASSRATGIPDR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPFTFGPGTKVEIK 330 CD70-33 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVMGRFTISRDNSKNTLYLQMN

- 113 041992

SLRAEDTAVYYCARHDYSNYAFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGASSRATGIPDR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPFTFGPGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 331 CD70-34 VH CDR1 TYAMS 332 CD70-34 VH CDR2 TISDSGGSTFYADSVMG 333 CD70-34 VH CDR3 HDYSNYAFFDY 334 CD70-34 VL CDR1 RASQSVSSNLA 335 CD70-34 VL CDR2 GAST RAT 336 CD70-34 VL CDR3 QQYYSTPFT 337 CD70-34 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVMGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYAFFDYWGQ GTLVTVSS 338 CD70-34 VL EIVLTQSPATLSVSPGERATLSCRASQS VS SNLAWYQQKPGQAPRLLIYGAS TRAT GIPARFSGSGSGTEFTLAISRLEPEDFA VYYCQQYYSTPFTFGGGTKVEIK 339 II CD70-34 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVMGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYAFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 114 041992

QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGASTRATGIPAR FSGSGSGTEFTLAISRLEPEDFAVYYCQ QYYSTPFTFGGGTKVEIK 340 CD70-34 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSTISDSGG STFYADSVMGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYAFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGASTRATGIPAR FSGSGSGTEFTLAISRLEPEDFAVYYCQ QYYSTPFTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 341 CD70-35 VH CDR1 TYAMS 342 CD70-35 VH CDR2 AISGSGGYTYYADSVEG 343 CD70-35 VH CDR3 HDYSNYAWFDP 344 CD70-35 VL CDR1 RASQSVSSAYLA 345 CD70-35 VL CDR2 GASS RAT 346 CD70-35 VL CDR3 QQFGSSPFT 347 CD70-35 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSS 348 CD70-35 VL EIVLTQSPGTLSLSPGERATLSCRASQS VS SAYLAWYQQKPGQAPRLLIYGAS SRA

- 115 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQFGSSPFTFGPGTKVEIK 349 I CD70-35 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVSSAY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQFGSSPFTFGPGTKVEIK 350 CD70-35 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVSSAY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQFGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 351 CD70-36 VH CDR1 SYAMS 352 CD70-36 VH CDR2 AISGSGGRTYYADSVKG 353 CD70-36 VH CDR3 HDYSNYPYFDY 354 CD70-36 VL CDR1 RASQSVRGSYLA 355 CD70-36 VL CDR2 SASS RAT 356 CD70-36 VL CDR3 QQYGDSPFT

- 116 041992

357 CD70-36 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGQGLEWVSAISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 358 CD70-36 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRGSYLAWYQQKPGQAPRLLIYSASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDSPFTFGPGTKVEIK 359 II CD70-36 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGQGLEWVSAISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGSY LAWYQQKPGQAPRLLIYSASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDSPFTFGPGTKVEIK 360 CD70-36 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGQGLEWVSAISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGSY LAWYQQKPGQAPRLLIYSASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 117 041992

YYCVLWYSNRWVFGGGTKLTVL 361 CD70-37 VH CDR1 SYAMS 362 CD70-37 VH CDR2 AIGDGGGYTYYADSVKG 363 CD70-37 VH CDR3 HDYSNYPYFDY 364 CD70-37 VL CDR1 RASQGVRSSYFA 365 CD70-37 VL CDR2 GAST RAT 366 CD70-37 VL CDR3 QQYGSSPPT 367 CD70-37 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 368 CD70-37 VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSSYFAWYQQKPGQAPRLLIYGASTRA TGIPARFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSPPTFGQGTKVEIK 369 II CD70-37 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIK 370 CD70-37 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 118 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 371 CD70-38 VH CDR1 SYAMS 372 CD70-38 VH CDR2 AISGSGGRTFYADSVEG 373 CD70-38 VH CDR3 HDYSNYPYFDY 374 CD70-38 VL CDR1 RASQSIRSNYLA 375 CD70-38 VL CDR2 GASS RAT 376 CD70-38 VL CDR3 QQYGSSPPS 377 CD70-38 vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 378 CD70-38 VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPPSFGQGTKVEIK 379 II CD70-38 scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTKVEIK 380 CD70-38 bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN

- 119 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 381 CD70-39 VH CDR1 SYAMS 382 CD70-39 VH CDR2 AISGSGGGTFYADSVEG 383 CD70-39 VH CDR3 HDYSNYPYFDY 384 CD70-39 VL CDR1 RASQSVRSSYLA 385 CD70-39 VL CDR2 GASS RAT 386 CD70-39 VL CDR3 QQYGDLPFT 387 CD70-39 vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSS 388 CD70-39 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGPGTKVEIK 389 VI CD70-39 scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 120 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIK 390 CD70-39 bispecific molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 391 CD70-40 VH CDR1 SYAMS 392 CD70-40 VH CDR2 AISGSGGRTFYADSVEG 393 CD70-40 VH CDR3 HDYSNYPYFDY 394 CD70-40 VL CDR1 RASQSIRSSYLA 395 CD70-40 VL CDR2 GASS RAT 396 CD70-40 VL CDR3 QQYGDLPFT 397 CD70-40 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 398 CD70-40 VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSSYLAWYQQKPGQAPRLLIYGASSRA

- 121 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVDIK 399 II CD70-40 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVDIK 400 CD70-40 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 401 CD70-41 VH CDR1 SYAMS 402 CD70-41 VH CDR2 AISGSGGRTFYADSVEG 403 CD70-41 VH CDR3 HDYSNYPYFDY 404 CD70-41 VL CDR1 RASQSVRSSYLA 405 CD70-41 VL CDR2 GASS RAT 406 CD70-41 VL CDR3 QQYGDLPFT

- 122 041992

407 CD70-41 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 408 CD70-41 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVDIK 409 II CD70-41 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVDIK 410 CD70-41 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 123 041992

YYCVLWYSNRWVFGGGTKLTVL 411 CD70-42 VH CDR1 TYAMS 412 CD70-42 VH CDR2 LISGSGGRTYYADSVKG 413 CD70-42 VH CDR3 HDYSNYPYFDY 414 CD70-42 VL CDR1 RASQGVRSSYLA 415 CD70-42 VL CDR2 GASS RAT 416 CD70-42 VL CDR3 QQYGSSPPT 417 CD70-42 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 418 CD70-42 VL EIVLTQSPGTLSLSPGERATLSCRASQG VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTFGGGTKVDIK 419 II CD70-42 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIK 420 CD70-42 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 124 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 421 CD70-43 VH CDR1 SYAMS 422 CD70-43 VH CDR2 AISGSGGRTFYADSVEG 423 CD70-43 VH CDR3 HDYSNYPYFDY 424 CD70-43 VL CDR1 RASQSVRSNYLA 425 CD70-43 VL CDR2 GASS RAT 426 CD70-43 VL CDR3 QQYGSSPPT 427 CD70-43 vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 428 CD70-43 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTFGGGTKVDIK 429 II CD70-43 scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIK 430 CD70-43 bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN

- 125 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 431 CD70-44 VH CDR1 SYAMS 432 CD70-44 VH CDR2 VISDSGGITDFADSVKG 433 CD70-44 VH CDR3 HDYSNYFFFDY 434 CD70-44 VL CDR1 RASQDISNYLN 435 CD70-44 VL CDR2 AASSLQS 436 CD70-44 VL CDR3 QQSYISPPT 437 CD70-44 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFIISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 438 CD70-44 VL DIQMTQSPSSLSASVGDRVTITCRASQD ISNYLNWYQQKSGKAPELLIYAASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYISPPTFGQGTKVEIK 439 I CD70-44 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFIISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT

- 126 041992

QSPSSLSASVGDRVTITCRASQDISNYL NWYQQKSGKAPELLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYISPPTFGQGTKVEIK 440 CD70-44 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFIISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQDISNYL NWYQQKSGKAPELLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYISPPTFGQGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 441 CD70-45 VH CDR1 SYAMS 442 CD70-45 VH CDR2 VISDSGGITDFADSVKG 443 CD70-45 VH CDR3 HDYSNYFFFDY 444 CD70-45 VL CDR1 RASQSISSYLN 445 CD70-45 VL CDR2 AASSLQS 446 CD70-45 VL CDR3 QQSYISPPT 447 CD70-45 vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 448 CD70-45 VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS

- 127 041992

GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYISPPTFGQGTKVEIK 449 I CD70-45 scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYISPPTFGQGTKVEIK 450 CD70-45 bispecific molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYISPPTFGQGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 451 CD70-46 VH CDR1 SYAMS 452 CD70-46 VH CDR2 VISGSGGRTDYADSVKG 453 CD70-46 VH CDR3 HDYSNRFYFDY 454 CD70-46 VL CDR1 RASQSISSYLN 455 CD70-46 VL CDR2 AASSLQS 456 CD70-46 VL CDR3 QQSYSAPPT

- 128 041992

457 CD70-46 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQVPGKGLEWVSVISGSGG RTDYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNRFYFDYWGQ GTLVTVSS 458 CD70-46 VL DIQMTQSPSSLSASVGDRVSITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSAPPTFGGGTKVEIK 459 II CD70-46 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQVPGKGLEWVSVISGSGG RTDYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNRFYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVSITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSAPPTFGGGTKVEIK 460 CD70-46 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQVPGKGLEWVSVISGSGG RTDYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNRFYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVSITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSAPPTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY

- 129 041992

YCVLWYSNRWVFGGGTKLTVL 461 CD70-47 VH CDR1 SYAMS 462 CD70-47 VH CDR2 VISDSGGITDYADSVKG 463 CD70-47 VH CDR3 HDYSNRYYFDY 464 CD70-47 VL CDR1 RASQSISSYLN 465 CD70-47 VL CDR2 AASSLQS 466 CD70-47 VL CDR3 QQSYSTPLT 467 CD70-47 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDYADSVKGRFTISRDNSKNTLYLQMN SLRAEDRAVYYCARHDYSNRYYFDYWGQ GTLVTVSS 468 CD70-47 VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSTPLTFGGGTKVEIK 469 I CD70-47 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDYADSVKGRFTISRDNSKNTLYLQMN SLRAEDRAVYYCARHDYSNRYYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPLTFGGGTKVEIK 470 CD70-47 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDYADSVKGRFTISRDNSKNTLYLQMN SLRAEDRAVYYCARHDYSNRYYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPLTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY

- 130 041992

AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGDEQAPRGLIGGTKFLAPGT PARFSGSLLGPEALTLSGVQ 471 CD70-48 VH CDR1 SYAMS 472 CD70-48 VH CDR2 VISDSGGITDFADSVKG 473 CD70-48 VH CDR3 HDYSNYFFFDY 474 CD70-48 VL CDR1 RASQGISNYLA 475 CD70-48 VL CDR2 AASILQS 476 CD70-48 VL CDR3 QQYFAYPIT 477 CD70-48 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 478 CD70-48 VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASILQS GVPSKFSGSGSGTDFTLTISSLQPEDFA IYYCQQYFAYPITFGQGTRLEIK 479 I CD70-48 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIK 480 CD70-48 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN

- 131 041992

SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 481 CD70-49 VH CDR1 SYAMS 482 CD70-49 VH CDR2 VISDSGGITDFADSVKG 483 CD70-49 VH CDR3 HDYSNYFFFDY 484 CD70-49 VL CDR1 RASQSISSYLN 485 CD70-49 VL CDR2 AASSLQS 486 CD70-49 VL CDR3 QQSYSTPIT 487 CD70-49 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRS TISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 488 CD70-49 VL DIQMTQSPSSVSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSTPITFGQGTRLEIK 489 I CD70-49 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRS TISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT

- 132 041992

QSPSSVSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPITFGQGTRLEIK 490 CD70-49 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRS ТISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSVSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 491 CD70-50 VH CDR1 TYAMS 492 CD70-50 VH CDR2 AISGSGGYTYYADSVEG 493 CD70-50 VH CDR3 HDYSNYAWFDP 494 CD70-50 VL CDR1 RASQSISSYLN 495 CD70-50 VL CDR2 AASSLQS 496 CD70-50 VL CDR3 QQSYSTPFT 497 CD70-50 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSS 498 CD70-50 VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS

- 133 041992

GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSTPFTFGPGTRLEIK 499 I CD70-50 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPFTFGPGTRLEIK 500 CD70-50 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQSISSYL NWYQQKPGKAPKLLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPFTFGPGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 501 CD70-51 VH CDR1 TDGYYWS 502 CD70-51 VH CDR2 YIYYSGSTNYNPSLKS 503 CD70-51 VH CDR3 GIGLGFEY 504 CD70-51 VL CDR1 GGNNIGSKSVH 505 CD70-51 VL CDR2 DDSDRPS 506 CD70-51 VL CDR3 QVWDRSSDQDW

- 134 041992

507 CD70-51 vh QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKGLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL S SVTAADTAVYYCARGIGLGFEYWGQGT LVTVSS 508 CD70-51 VL SYVLTQLTSVSVAPGQTARITCGGNNIG SKSVHWYQQKPGQAPVLWYDDSDRPSG IPERFSGSNSGNTATLTISRVEAGDEAD FYCQVWDRSSDQDWFGGGTKLTVL 509 VI CD70-51 scFv QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKGLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL S SVTAADTAVYYCARGIGLGFEYWGQGT LVTVSSGGGGSGGGGSGGGGSSYVLTQL TSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLWYDDSDRPSGIPERFSG SNSGNTATLTISRVEAGDEADFYCQVWD RSSDQDWFGGGTKLTVL 510 CD70-51 bispecificity molecular molecule QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKGLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL S SVTAADTAVYYCARGIGLGFEYWGQGT LVTVSSGGGGSGGGGSGGGGSSYVLTQL TSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLWYDDSDRPSGIPERFSG SNSGNTATLTISRVEAGDEADFYCQVWD RSSDQDWFGGGTKLTVLSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY

- 135 041992

YCVLWYSNRWVFGGGTKLTVL 511 CD70-52 VH CDR1 TDGYYWS 512 CD70-52 VH CDR2 YIYYSGSTNYNPSLKS 513 CD70-52 VH CDR3 GIGLGFEY 514 CD70-52 VL CDR1 GGNNIGSKSVH 515 CD70-52 VL CDR2 DDSDRPS 516 CD70-52 VL CDR3 QVWDRSSDQDW 517 CD70-52 vh QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKGLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL S SVTAADTAVYYCARGIGLGFEYWGQGT LVTVSS 518 CD70-52 VL SYVLTQLSSVSVAPGQTARITCGGNNIG SKSVHWYQQKPGQAPVLWYDDSDRPSG IPERFSGSNSGNTATLTISRVEAGDEAD YYCQVWDRSSDQDWFGGGTKLTVL 519 I CD70-52 scFv QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKGLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL S SVTAADTAVYYCARGIGLGFEYWGQGT LVTVSSGGGGSGGGGSGGGGSSYVLTQL SSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLWYDDSDRPSGIPERFSG SNSGNTATLTISRVEAGDEADYYCQVWD RSSDQDWFGGGTKLTVL 520 CD70-52 bispecificity molecular molecule QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKGLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL S SVTAADTAVYYCARGIGLGFEYWGQGT LVTVSSGGGGSGGGGSGGGGSSYVLTQL SSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLWYDDSDRPSGIPERFSG SNSGNTATLTISRVEAGDEADYYCQVWD RSSDQDWFGGGTKLTVLSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY

- 136 041992

AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGDEAPRGLIGGTKFLAPGT PARFSGSLLGPEGALTKWGGLY 521 CD70-53 VH CDR1 SYAMS 522 CD70-53 VH CDR2 AISGSGGRTFYADSVEG 523 CD70-53 VH CDR3 HDYSNYPYFDY 524 CD70-53 VL CDR1 RASQSVRSSYLA 525 CD70-53 VL CDR2 GASS RAT 526 CD70-53 VL CDR3 QQYGSSPPT 527 CD70-53 vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 528 CD70-53 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTFGGGTRLEIK 529 II CD70-53 scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIK 530 CD70-53 bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN

- 137 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 531 CD70-54 VH CDR1 I YAMS 532 CD70-54 VH CDR2 AIGDSGGSTFYADSVKG 533 CD70-54 VH CDR3 HDYSNYPYFDY 534 CD70-54 VL CDR1 RASQSVRSSYVA 535 CD70-54 VL CDR2 GASS RAT 536 CD70-54 VL CDR3 QQYGDLPFT 537 CD70-54 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 538 CD70-54 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYVAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTRLEIK 539 VI CD70-54 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT

- 138 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY VAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIK 540 CD70-54 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGRGLEWVSAIGDSGG STFYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 541 CD70-55 VH CDR1 SYGMH 542 CD70-55 VH CDR2 VISYDGSNKKYYADSVKG 543 CD70-55 VH CDR3 GRYYGSGNYNHGMDV 544 CD70-55 VL CDR1 RASQSISSYLN 545 CD70-55 VL CDR2 AASSLQS 546 CD70-55 VL CDR3 QQSYSTPFT 547 CD70-55 vh QVQLVE S GGGWQPGRS LRL S CAAS G FM 548 CD70-55 VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQRPGRAPRLLIYAASSLQS

- 139 041992

GVPSRFSGRGSGTDFTLTISSLQPEDFA TYYCQQSYSTPFTFGPGTKVEIK 549 VII CD70-55 scFv QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIK 550 CD70-55 bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 551 CD70-56 VH CDR1 SYGMH 552 CD70-56 VH CDR2 VISYDGSNKKYYADSVKG 553 CD70-56 VH CDR3 GRYYGSGSYNYGMDV 554 CD70-56 VL CDR1 RASQSIFDYLN 555 CD70-56 VL CDR2 AASSLQS 556 CD70-56 VL CDR3 QQSYSTPLT

- 140 041992

557 CD70-56 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARGRYYGSGSYNYGMD VWGQGTTVTVSS 558 CD70-56 VL DIQMTQSPSSLSASVGDRVTITCRASQS IFDYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGSGFGTDFTLTISSLQPEDFA TYYCQQSYSTPLTFGGGTKLEIK 559 VII CD70-56 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARGRYYGSGSYNYGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI FDYLNWYQQRPGRAPRLLIYAASSLQSG VPSRFSGSGFGTDFTLTISSLQPEDFAT YYCQQSYSTPLTFGGGTRLEIR 560 CD70-56 bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FT FSSYGMHWVRQAPGRGLEWVAVISYDGS NRYYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARGRYYGSGSYNYGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI FDYLNWYQQRPGRAPRLLIYAASSLQSG VPSRFSGSGFGTDFTLTISSLQPEDFAT YYCQQSYSTPLTFGGGTRLEIRSGGGGS EVQLVESGGGLVQPGGSLRLSCAASGFT FNRYAMNWVRQAPGRGLEWVARIRSRYN NYATYYADSVRDRFTISRDDSRNTAYLQ MNNLRTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQRPGQAPRGLIGGTRFL APGTPARFSGSLLGGRAALTLSGVQPED

- 141 041992

EAEYYCVLWYSNRWVFGGGTKLTVL 561 CD70-57 VH CDR1 SYGMH 562 CD70-57 VH CDR2 VIWYDGSSEYYADSVKG 563 CD70-57 VH CDR3 DNSYNYYGMDV 564 CD70-57 VL CDR1 TGSSSNIGAAYDVH 565 CD70-57 VL CDR2 VNSHRPP 566 CD70-57 VL CDR3 LSYDNSLSGSV 567 CD70-57 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVIWYDGS SEYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSYNYYGMDVWGQ GTTVTVSS 568 CD70-57 VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAAYDVHWYQQFPGTAPKLLIYVNSHR PPGVPDRFSGSKSGTSASLAITGLQAED EADYYCLSYDNSLSGSVFGGGTKLTVL 569 I CD70-57 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVIWYDGS SEYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSYNYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAAY DVHWYQQFPGTAPKLLIYVNSHRPPGVP DRFSGSKSGTSASLAITGLQAEDEADYY CLSYDNSLSGSVFGGGTKLTVL 570 CD70-57 bispecific molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVIWYDGS SEYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSYNYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAAY DVHWYQQFPGTAPKLLIYVNSHRPPGVP DRFSGSKSGTSASLAITGLQAEDEADYY CLSYDNSLSGSVFGGGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT

- 142 041992

FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTVVTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 571 CD70-58 VH CDR1 SSSYYWG 572 CD70-58 VH CDR2 SIYHSGGTYFNPSLKS 573 CD70-58 VH CDR3 HYEILTGYYPDVFDI 574 CD70-58 VL CDR1 RASQSISSYLN 575 CD70-58 VL CDR2 AASNLQS 576 CD70-58 VL CDR3 QQSFSSPRT 577 CD70-58 vh QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSS 578 CD70-58 VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIK 579 II CD70-58 scFv QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIK 580 CD70-58 bispecificity molecular molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL

- 143 041992

SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTVVTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVL 581 CD70-59 VH CDR1 GFYWS 582 CD70-59 VH CDR2 EIDHSSGSTNYNPSLKS 583 CD70-59 VH CDR3 NGYSGYLFDY 584 CD70-59 VL CDR1 RASQIISSYLN 585 CD70-59 VL CDR2 GASSMQS 586 CD70-59 VL CDR3 QQSYSIPRT 587 CD70-59 vh QVQLQQWGAGLLKPSETLSLTCAVYDGS VSGFYWSWIRQPPGKGLEWIGEIDHSGS TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADSAVYYCARNGYSGYLFDYWGQGT LVTVSS 588 CD70-59 VL DIQMTQSPSSLSASVGDRVTITCRASQI IS SYLNWYQQKPGKAPKVLIYGAS SMQS GVPSRFSGSGYGTDFTLTISSLQPEDFA TYYCQQSYSIPRTFGQGTKLEIK 589 II CD70-59 scFv QVQLQQWGAGLLKPSETLSLTCAVYDGS VSGFYWSWIRQPPGKGLEWIGEIDHSGS TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADSAVYYCARNGYSGYLFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDIQMTQS

- 144 041992

PSSLSASVGDRVTITCRASQIISSYLNW YQQKPGKAPKVLIYGASSMQSGVPSRFS GSGYGTDFTLTISSLQPEDFATYYCQQS YSIPRTFGQGTKLEIK 590 CD70-59 bispecific molecule QVQLQQWGAGLLKPSETLSLTCAVYDGS VSGFYWSWIRQPPGKGLEWIGEIDHSGS TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADSAVYYCARNGYSGYLFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDIQMTQS PSSLSASVGDRVTITCRASQIISSYLNW YQQKPGKAPKVLIYGASSMQSGVPSRFS GSGYGTDFTLTISSLQPEDFATYYCQQS YSIPRTFGQGTKLEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY ADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGTKLTVL 591 CD70-60 VH CDR1 TYYWS 592 CD70-60 VH CDR2 RIYPTGITNYNPSLKS 593 CD70-60 VH CDR3 DRRFLEPSYYYYYGMDV 594 CD70-60 VL CDR1 RSSQSLLHSNGYNYLD 595 CD70-60 VL CDR2 LGSNRAS 596 CD70-60 VL CDR3 MQGLRTPFT 597 CD70-60 vh QVQLQESGPGLVKPSETLSLTTCTVSGDS ISTYYWSWIRQPAGKGLEWIGRIYPTGI TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADTAVYYCARDRRFLEPSYYYYYGM DVWGQGTTVTVSS 598 CD70-60 VL DIVLTQSPLSLPVTPGEPASISCRSSQS LLHSNGYNYLDWYLQKPGQSPQLLIYLG

- 145 041992

SNRASGVPDRFSGSVSGTDFTLKISRVE AEDVGVYYCMQGLRTPFTFGPGTKLEIK 599 VII CD70-60 scFv QVQLQESGPGLVKPSETLSLTCTVSGDS ISTYYWSWIRQPAGKGLEWIGRIYPTGI TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADTAVYYCARDRRFLEPSYYYYYGM DVWGQGTTVTVSSGGGGSGGGGSGGGGS DIVLTQSPLSLPVTPGEPASISCRSSQS LLHSNGYNYLDWYLQKPGQSPQLLIYLG SNRASGVPDRFSGSVSGTDFTLKISRVE AEDVGVYYCMQGLRTPFTFGPGTKLEIK 600 CD70-60 bispecificity molecular molecule QVQLQESGPGLVKPSETLSLTCTVSGDS ISTYYWSWIRQPAGKGLEWIGRIYPTGI TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADTAVYYCARDRRFLEPSYYYYYGM DVWGQGTTVTVSSGGGGSGGGGSGGGGS DIVLTQSPLSLPVTPGEPASISCRSSQS LLHSNGYNYLDWYLQKPGQSPQLLIYLG SNRASGVPDRFSGSVSGTDFTLKISRVE AEDVGVYYCMQGLRTPFTFGPGTKLEIK SGGGGSEVQLVESGGGLVQPGGSLKLSC AASGFTFNKYAMNWVRQAPGKGLEWVAR IRSKYNNYATYYADSVKDRFTISRDDSK NTAYLQMNNLKTEDTAVYYCVRHGNFGN SYISYWAYWGQGTLVTVSSGGGGSGGGG SGGGGSQTWTQEPSLTVSPGGTVTLTC GS S TGAVT S GNYPNWVQQKPGQAPRGLI GGTKFLAPGTPARFSGSLLGGKAALTLS GVQPEDEAEYYCVLWYSNRWVFGGGTKL TVL 601 CD70-61 VH CDR1 SYAMS 602 CD70-61 VH CDR2 VISDSGGITDFADSVKG 603 CD70-61 VH CDR3 HDYSNYFFFDY 604 CD70-61 VL CDR1 RASQSISNYLN 605 CD70-61 VL CDR2 AASSLQS

- 146 041992

606 CD70-61 VL CDR3 QQSYIIPPPT 607 CD70-61 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 608 CD70-61 VL DIQMTQSPSSLSASVGDRITITCRASQS ISNYLNWYQQKPGKAPKLLISAASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYIIPPTFGQGTKVDIK 609 I CD70-61 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRITITCRASQSISNYL NWYQQKPGKAPKLLISAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYIIPPTFGQGTKVDIK 610 CD70-61 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRITITCRASQSISNYL NWYQQKPGKAPKLLISAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYIIPPTFGQGTKVDIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT

- 147 041992

PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 611 CD70-62 VH CDR1 SYSMN 612 CD70-62 VH CDR2 YISSSGGYIYYADSVKG 613 CD70-62 VH CDR3 GDYSNYAYFDY 614 CD70-62 VL CDR1 RASQGISNYLA 615 CD70-62 VL CDR2 AASTLQS 616 CD70-62 VL CDR3 QQYYSTPLT 617 CD70-62 vh EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSS 618 CD70-62 VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASTLQS GVPSRFSGSGSGTDFTLTISSLQAEDVA VYYCQQYYSTPLTFGGGTKVEIK 619 I CD70-62 scFv EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIK 620 CD70-62 bispecific molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIKSGGGGSEVQL

- 148 041992

VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 621 CD70-63 VH CDR1 TYTMN 622 CD70-63 VH CDR2 SISSSSGYIYYADSVKG 623 CD70-63 VH CDR3 GDYSNYLYFDL 624 CD70-63 VL CDR1 RASQSFRSSYLA 625 CD70-63 VL CDR2 GASS RAT 626 CD70-63 VL CDR3 QLYGSLPIT 627 CD70-63 vh EVQLVESGGGLVKPGGSLRLSCAASGIT FS TYTMNWVRQAPGKGLEWVS SIS S S S G YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDTAVYYCARGDYSNYLYFDLWGR GTLVTVSS 628 CD70-63 VL EIVLTQSPGTLSLSPGERATLSCRASQS FRSSYLAWYQQKPGQAPRLLIHGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQLYGSLPITFGQGTRLEIK 629 II CD70-63 scFv EVQLVESGGGLVKPGGSLRLSCAASGIT FS TYTMNWVRQAPGKGLEWVS SIS S S S G YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDTAVYYCARGDYSNYLYFDLWGR GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSFRSSY LAWYQQKPGQAPRLLIHGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QLYGSLPITFGQGTRLEIK 630 CD70-63 bispecificity chesky EVQLVESGGGLVKPGGSLRLSCAASGIT FS TYTMNWVRQAPGKGLEWVS SIS S S S G

- 149 041992

molecule YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDTAVYYCARGDYSNYLYFDLWGR GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSFRSSY LAWYQQKPGQAPRLLIHGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QLYGSLPITFGQGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 631 CD70-64 VH CDR1 VYAMS 632 CD70-64 VH CDR2 TISDSGGSTFYADSVKG 633 CD70-64 VH CDR3 HDYSNYAYFDY 634 CD70-64 VL CDR1 RASQSVRSSYLA 635 CD70-64 VL CDR2 GASS RAT 636 CD70-64 VL CDR3 QQYGDLPFT 637 CD70-64 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSS 638 CD70-64 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK 639 VI CD70-64 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ

- 150 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 640 CD70-64 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 641 CD70-65 VH CDR1 TYAMS 642 CD70-65 VH CDR2 AISGSGGYTYYADSVEG 643 CD70-65 VH CDR3 HDYSNYAWFDP 644 CD70-65 VL CDR1 RASQSVSSAYLA 645 CD70-65 VL CDR2 GASS RAT 646 CD70-65 VL CDR3 QQFGSSPFT 647 CD70-65 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSS 648 CD70-65 VL EIVLTQSPGTLSLSPGERATLSCRASQS

- 151 041992

VS SAYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQFGSSPFTFGCGTKVEIK 649 I CD70-65 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVSSAY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQFGSSPFTFGCGTKVEIK 650 CD70-65 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLDWVSAISGSGG YTYYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCASHDYSNYAWFDPWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVSSAY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQFGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 651 CD70-66 VH CDR1 SYAMS 652 CD70-66 VH CDR2 AISGSGGRTYYADSVKG 653 CD70-66 VH CDR3 HDYSNYPYFDY 654 CD70-66 VL CDR1 RASQSVRGSYLA 655 CD70-66 VL CDR2 SASSRAT

- 152 041992

656 CD70-66 VL CDR3 QQYGDSPFT 657 CD70-66 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGQCLEWVSAISGSGG RTYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 658 CD70-66 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRGSYLAWYQQKPGQAPRLLIYSASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDSPFTFGCGTKVEIK 659 II CD70-66 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGQCLEWVSAISGSGG RTYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGSY LAWYQQRPGQAPRLLIYSASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDSPFTFGCGTRVEIR 660 CD70-66 bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGQCLEWVSAISGSGG RTYYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGSY LAWYQQRPGQAPRLLIYSASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDSPFTFGCGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSKYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG

- 153 041992

TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 661 CD70-67 VH CDR1 SYAMS 662 CD70-67 VH CDR2 VISDSGGITDFADSVKG 663 CD70-67 VH CDR3 HDYSNYFFFDY 664 CD70-67 VL CDR1 RASQDISNYLN 665 CD70-67 VL CDR2 AASSLQS 666 CD70-67 VL CDR3 QQSYISPPT 667 CD70-67 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFIISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 668 CD70-67 VL DIQMTQSPSSLSASVGDRVTITCRASQD ISNYLNWYQQKSGKAPELLIYAASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYISPPTFGCGTKVEIK 669 I CD70-67 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFIISRDNSKNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQDISNYL NWYQQKSGKAPELLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYISPPTFGCGTKVEIK 670 CD70-67 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFIISRDNSKNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQDISNYL NWYQQKSGKAPELLIYAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYISPPTFGCGTKVEIKSGGGGSEVQL

- 154 041992

VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 671 CD70-68 VH CDR1 SYAMS 672 CD70-68 VH CDR2 VISDSGGITDFADSVKG 673 CD70-68 VH CDR3 HDYSNYFFFDY 674 CD70-68 VL CDR1 RASQGISNYLA 675 CD70-68 VL CDR2 AASILQS 676 CD70-68 VL CDR3 QQYFAYPIT 677 CD70-68 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 678 CD70-68 VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASILQS GVPSKFSGSGSGTDFTLTISSLQPEDFA IYYCQQYFAYPITFGCGTRLEIK 679 I CD70-68 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFATYYCQ QYFAYPITFGCGTRLEIK 680 CD70-68 bispecificity chesky EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG

- 155 041992

molecule ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 681 CD70-69 VH CDR1 TDGYYWS 682 CD70-69 VH CDR2 YIYYSGSTNYNPSLKS 683 CD70-69 VH CDR3 GIGLGFEY 684 CD70-69 VL CDR1 GGNNIGSKSVH 685 CD70-69 VL CDR2 DDSDRPS 686 CD70-69 VL CDR3 QVWDRSSDQDW 687 CD70-69 vh QVQLQESGPGLVKPSETLSLTTCTVSGGS VSTDGYYWSWIRQPPGKCLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL ISVTAADTAVYYCARGIGLGFEYWGQGT LVTVSS 688 CD70-69 VL SYVLTQLSSVSVAPGQTARITCGGNNIG SKSVHWYQQKPGQAPVLWYDDSDRPSG IPERFSGSNSGNTATLTISRVEAGDEAD YYCQVWDRSSDQDWFGCGTKLTVL 689 VI CD70-69 scFv QVQLQESGPGLVKPSETLSLTTCTVSGGS VSTDGYYWSWIRQPPGKCLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL ISVTAADTAVYYCARGIGLGFEYWGQGT

- 156 041992

LVTVSSGGGGSGGGGSGGGGSSYVLTQL SSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLWYDDSDRPSGIPERFSG SNSGNTATLTISRVEAGDEADYYCQVWD RSSDQDWFGCGTKLTVL 690 CD70-69 bispecific molecule QVQLQESGPGLVKPSETLSLTCTVSGGS VSTDGYYWSWIRQPPGKCLEWIGYIYYS GSTNYNPSLKSRVTISVDTSKNQFSLKL ISVTAADTAVYYCARGIGLGFEYWGQGT LVTVSSGGGGSGGGGSGGGGSSYVLTQL SSVSVAPGQTARITCGGNNIGSKSVHWY QQKPGQAPVLWYDDSDRPSGIPERFSG SNSGNTATLTISRVEAGDEADYYCQVWD RSSDQDWFGCGTKLTVLSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 691 CD70-70 VH CDR1 SYGMH 692 CD70-70 VH CDR2 VISYDGSNKKYYADSVKG 693 CD70-70 VH CDR3 GRYYGSGNYNHGMDV 694 CD70-70 VL CDR1 RASQSISSYLN 695 CD70-70 VL CDR2 AASSLQS 696 CD70-70 VL CDR3 QQSYSTPFT 697 CD70-70 vh QVQLVE S GGGWQPGRS LRL S CAAS G FM 698 CD70-70 VL DIQMTQSPSSLSASVGDRVTITCRASQS

- 157 041992

ISSYLNWYQQRPGRAPRLLIYAASSLQS GVPSRFSGRGSGTDFTLTISSLQPEDFA TYYCQQSYSTPFTFGCGTKVEIK 699 VII CD70-70 scFv QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQRPGRAPRLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTRVEIR 700 CD70-70 bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGRCLEWVAVISYDGS NRYYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQRPGRAPRLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTRVEIRSGGGGS EVQLVESGGGLVQPGGSLRLSCAASGFT FNRYAMNWVRQAPGRGLEWVARIRSRYN NYATYYADSVRDRFTISRDDSRNTAYLQ MNNLRTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQRPGQAPRGLIGGTRFL APGTPARFSGSLLGGRAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTRLTVL 701 CD70-71 VH CDR1 SYGMH 702 CD70-71 VH CDR2 VISYDGSNRYYADSVRG 703 CD70-71 VH CDR3 GRYYGSGSYNYGMDV 704 CD70-71 VL CDR1 RASQSIFDYLN 705 CD70-71 VL CDR2 AASSLQS

- 158 041992

706 CD70-71 VL CDR3 QQSYSTPLT 707 CD70-71 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGSYNYGMD VWGQGTTVTVSS 708 CD70-71 VL DIQMTQSPSSLSASVGDRVTITCRASQS IFDYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGSGFGTDFTLTISSLQPEDFA TYYCQQSYSTPLTFGCGTKLEIK 709 VII CD70-71 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGSYNYGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI FDYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGSGFGTDFTLTISSLQPEDFAT YYCQQSYSTPLTFGCGTKLEIK 710 CD70-71 bispecific molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGSYNYGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI FDYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGSGFGTDFTLTISSLQPEDFAT YYCQQSYSTPLTFGCGTKLEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL

- 159 041992

APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 711 CD70-72 VH CDR1 TYYWS 712 CD70-72 VH CDR2 RIYPTGITNYNPSLKS 713 CD70-72 VH CDR3 DRRFLEPSYYYYYGMDV 714 CD70-72 VL CDR1 RSSQSLLHSNGYNYLD 715 CD70-72 VL CDR2 LGSNRAS 716 CD70-72 VL CDR3 MQGLRTPFT 717 CD70-72 vh QVQLQESGPGLVKPSETLSLTTCTVSGDS ISTYYWSWIRQPAGKGLEWIGRIYPTGI TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADTAVYYCARDRRFLEPSYYYYYGM DVWGQGTTVTVSS 718 CD70-72 VL DIVLTQSPLSLPVTPGEPASISCRSSQS LLHSNGYNYLDWYLQKPGQSPQLLIYLG SNRASGVPDRFSGSVSGTDFTLKISRVE AEDVGVYYCMQGLRTPFTFGCGTKLEIK 719 VII CD70-72 scFv QVQLQESGPGLVKPSETLSLTCTVSGDS ISTYYWSWIRQPAGKGLEWIGRIYPTGI TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADTAVYYCARDRRFLEPSYYYYYGM DVWGQGTTVTVSSGGGGSGGGGSGGGGS DIVLTQSPLSLPVTPGEPASISCRSSQS LLHSNGYNYLDWYLQKPGQSPQLLIYLG SNRASGVPDRFSGSVSGTDFTLKISRVE AEDVGVYYCMQGLRTPFTFGCGTKLEIK 720 CD70-72 bispecific molecule QVQLQESGPGLVKPSETLSLTCTVSGDS ISTYYWSWIRQPAGKGLEWIGRIYPTGI TNYNPSLKSRVTISVDTSKNQFSLKLSS VTAADTAVYYCARDRRFLEPSYYYYYGM DVWGQGTTVTVSSGGGGSGGGGSGGGGS DIVLTQSPLSLPVTPGEPASISCRSSQS LLHSNGYNYLDWYLQKPGQSPQLLIYLG SNRASGVPDRFSGSVSGTDFTLKISRVE AEDVGVYYCMQGLRTPFTFGCGTKLEIK

- 160 041992

SGGGGSEVQLVESGGGLVQPGGSLKLSC AASGFTFNKYAMNWVRQAPGKGLEWVAR IRSKYNNYATYYADSVKDRFTISRDDSK NTAYLQMNNLKTEDTAVYYCVRHGNFGN SYISYWAYWGQGTLVTVSSGGGGSGGGG SGGGGSQTWTQEPSLTVSPGGTVTLTC GS S TGAVT S GNYPNWVQQKPGQAPRGLI GGTKFLAPGTPARFSGSLLGGKAALTLS GVQPEDEAEYYCVLWYSNRWVFGGGTKL TVL 721 CD70-73 VH CDR1 SYSMN 722 CD70-73 VH CDR2 YISSSGGYIYYADSVKG 723 CD70-73 VH CDR3 GDYSNYAYFDY 724 CD70-73 VL CDR1 RASQGISNYLA 725 CD70-73 VL CDR2 AASTLQS 726 CD70-73 VL CDR3 QQYYSTPLT 727 CD70-73 vh EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSS 728 CD70-73 VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASTLQS GVPSRFSGSGSGTDFTLTISSLQAEDVA VYYCQQYYSTPLTFGCGTKVEIK 729 I CD70-73 scFv EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIK 730 CD70-73 bispecificity EVQLVESGGGLVKPGGSLRLSCAASGFT

- 161 041992

chesky molecule FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 731 CD70-74 VH CDR1 SYAMS 732 CD70-74 VH CDR2 AISGSGGSTFYADSVQG 733 CD70-74 VH CDR3 HDYSNYPYFDY 734 CD70-74 VL CDR1 RASQSVRGNYLA 735 CD70-74 VL CDR2 GASS RAT 736 CD70-74 VL CDR3 QQYGYSPFT 737 CD70-74 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 738 CD70-74 VL EIVLTQSPGTLSLSPGERATLSCRASQS VRGNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPFTFGPGTKVDIK 739 II CD70-74 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN

- 162 041992

SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVDIK 740 CD70-74 bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 741 - CD70 person a Human MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICSPASRSI SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNTDETFFGVQWVRP 742 - CD70 ECD man a (ak Human QAQQQLPLESLGWDVAELQLNHTGPQQD PRLYWQGGPALGRS FLHGPELDKGQLRI HRDGIYMVHIQVTLAICSSTTASRHHPT TLAVGICSPASRSISLLRLSFHQGCTIA

- 163 041992

43-193) SQRLTPLARGDTLCTNLTGTLLPSRNTD ETFFGVQWVRP 743 - HuCD70-E1 (ak 4362) Human QAQQQLPLESLGWDVAELQL 744 - Hu CD70-E2 (ak 63- 84) Human NHTGPQQDPRLYWQGGPALGRS 745 - HuCD70-E3 (ak 85109) Human FLHGPELDKGQLRIHRDGIYMVHIQ 746 - Hu CD70-E4 (ac YO134) Human VTLAICSSTTASRHHPTTLAVGICS 747 - Hu CD70-E5 (ak 135151) Human PASRISSLLRLS FHQGC 748 - Hu CD70-E6 (ak 152175) Human TIASQRLTPLARGDTLCTNLTGTL 749 - Hu CD70-E7 (ak 176193) Human LPSRNTDETFFGVQWVRP 750 - Hu Human QAQQQLPLESLGWDVAELQLNHTGPQQD

- 164 041992

CD70- El+2 (ak 43- 84) PRLYWQGGPALGRS 751 - Hu CD70- EZ + 4 (ak 85- 134) Human FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICS 752 - Hu CD70- E4 + 5 (ak IO151) Human VTLAICSSTTASRHHPTTLAVGICSPAS RSISLRLSFHQGC 753 - Hu CD70- E5+6 (ak 135175) Human PASRSISSLLRLSFHQGCTIASQRLTPLA RGDTLCTNLTGTL 754 - Hu CD70- E6+7 (ak 152193) Human TIASQRLTPLARGDTLCTNLTGTLLPSR NTDETFFGVQWVRP 755 - CD70 macaque macaques MPEEGSGCAVRRRPYACVLRAAWPLVA GLAICLWCVQRLSRAQQLPLESLGWD IAELQLNHTGPQQDPRLYWQGGPALGRS FLRGPELDKGQLRIRRDGIYMVHIQVTL AICSSTSTSRHHHPTTLAVGICSPASRS ISLLRLSFHQGCTIASQRLTPLARGDTL CTNLTGTLLPSRNTDETFFGVQWVRP 756 - CD70 macaques RAQQQLPLESLGWDIAELQLNHTGPQQD

- 165 041992

Macaque ECD PRLYWQGGPALGRS FLRGPELDKGQLRI RRDGIYMVHIQVTLAICSSTSTSRHHHP TTLAVGICSPASRSISLLRLSFHQGCTI ASQRLTPLARGDTLCTNLTGTLLPSRNT DETFFGVQWVRP 757 - CD70 mice mouse MPEEGRCPCPWVRWSGTAFQRQWPWLLLV VFITVFCCWFHCSGLLSKQQQRLLEHPE PHTAELQLNLTVPRKDPTLRWGAGPALG RSFTTHGPELEEGHLRIHQDGLYRLHIQV TLANCSSPGSTLQHRATLAVGICSPAAH GISLLRGRFGQDCTVALQRLTYLVHGDV LCTNLTLPLLPSRNADETFFGVQWICP 758 - CD70 Mouse ECD mouse SKQQQRLLEHPEPHTAELQLNLTVPRKD PTLRWGAGPALGRS FTHGPELEEGHLRI HQDGLYRLHIQVTLANCSSPGSTLQHRA TLAVGICSPAAHGISLLRGRFGQDCTVA LQRLTYLVHGDVLCTNLTLPLLPSRNAD ETFFGVQWICP 759 - HuCD70 mu El art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFASKQQQRLLEHPEPH TAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICSPASRSI SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNTDETFFGVQLDWVRPGGGGSTK 760 - HuCD70 mu E2 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFAQAQQQLPLESLGWD VAELQLNLTVPRKDPTLRWGAGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICSPASRSI SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNTDETFFGVQWVRPGGG GSGKST 761 - HuCD70 art MPEGSGCSVRRRPYGCVLRAALVPLVA

- 166 041992

mu EZ other GLVICLWCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FTHGPELEEGHLRIHQDGLYRLHIQVTL AICSSTTASRHHPTTLAVGICSPASRS! SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNTDETFFGVQWVRPGGG GSGKPIPNPLLGLDST 762 - HuCD70 mu E4 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL ANCSSPGSTLQHRATLAVGICSPASRSI SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPLSRNTDETFFGVQWVRPGPLST 763 - HuCD70 mu E6 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICSPASRSI SLLRLSFHQGCTVALQRLTYLVHGDVLC TNLTLPLSRNTDETFFGVQWVRPGPIST 764 - HuCD70 mu E7 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICSPASRS! SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNADETFFGVQWICPGGG GSGKPIPNPLLGLDST 765 - HuCD70 mu El+2 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLWCIQRFASKQQQRLLEHPEPH TAELQLNLTVPRKDPTLRWGAGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL

- 167 041992

AICSSTTASRHHPTTLAVGICSPASRS! SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNTDETFGVQWVRPGGG GSGKPIPNPLLGLDST 766 - HuCD70 mu E3+4 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLVVCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FTHGPELEEGHLRIHQDGLYRLHIQVTL ANCSSPGSTLQHRATLAVGICSPASRSI SLLRLSFHQGCTIASQRLTPLARGDTLC TNLTGTLLPSRNTDETFFGVQWVRPGGG GSGKST 767 - HuCD70 mu E 4 + 5 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLVVCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL ANCSSPGSTLQHRATLAVGICSPAAHGI SLLRGRFGQDCTIASQRLTPLARGDTLC TNLTGTLLPLSRNTDETFFGVQWVRPGPLSTG 768 - HuCD70 mu E6+7 art other MPEEGSGCSVRRRPYGCVLRAALVPLVA GLVICLVVCIQRFAQAQQQLPLESLGWD VAELQLNHTGPQQDPRLYWQGGPALGRS FLHGPELDKGQLRIHRDGIYMVHIQVTL AICSSTTASRHHPTTLAVGICSPASRSI SLLRLSFHQGCTVALQRLTYLVHGDVLC TNLTLPLPSRNADETFFGVQWICPGPILD GVQWICPGPIST 769 - CD40L Human MIETYNQTSPRSAATGLPISMKIFMYLL TVFLITQMIGSALFAVYLHRRLDKIEDE RNLHEDFVFMKTIQRCNTGERSLSLLNC EEIKSQFEGFVKDIMLNKEETKKENSFE MQKGDQNPQIAAHVISEASSKTTSVLQW AEKGYYTMSNNLVTLENGKQLTVKRQGL YYIYAQVTFCSNREASSQAPFIASLCLK

- 168 041992

SPGRFERILLRAANTHSSAKPCGQQSIH LGGVFELQPGASVFVNVTDPSQVSHGTG FTSFGLLKL 770 - linker 1 art naya GGGG 771 - linker 2 art naya GGGGS 772 - linker 3 art naya GGGGQ 773 - linker 4 art naya SGGGGS 774 - linker 5 art naya PGGGGS 775 - linker 6 art naya PGGDGS 776 - linker 7 art naya GGGGSGGGS 777 - linker 8 art naya GGGGSGGGGS 778 - linker 9 art naya GGGGSGGGGSGGGGS 779 - Hexagi stidine art naya NNNN 780 - AI56 art naya RDWDFDVFGGGTPVGG 781 - Linear th FcRn VR art naya QRFVTGHFGGLXPANG 782 - Linear th FcRn BP-Y art naya QRFVTGHFGGLYPANG 783 - Linear th FcRn VR-N art naya QRFVTGHFGGLHPANG 784 - Cow art TGHFGGLHP

- 169 041992

FcRn BP-H other 785 - Cyclic cue FcRn BP-N art other QRFCTGHFGGLHPCNG 786 - HALB Human DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKEТСFAEЕGKKLVAASQAALGL 787 - HALB option 1 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP

- 170 041992

KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA GTFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAAMDDFAAFVEKCCK ADDKEТСFAEЕGKKLVAASQAALGL 788 - HALB option 2 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 789 - HALB art DAHKSEVAHRFKDLGEENFKALVLIAFA

- 171 041992

option 3 other QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPHLVAASKAALGL 790 - HALB option 4 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST

- 172 041992

PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALGVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 791 - HALB option 5 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 792 - HALB option 6 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP

- 173 041992

KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPHLVAASQAALGL 793 - HALB option 7 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPHLVAASKAALGL 794 - HALB art DAHKSEVAHRFKDLGEENFKALVLIAFA

- 174 041992

option 8 other QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKEТСFAEEGPKLVAASKAALGL 795 - HALB option 9 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQCPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST

- 175 041992

PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPKLVAASKAALGL 796 - HALB option 10 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGKKLVAASQAALGL 797 - HALB option eleven art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP

- 176 041992

KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA GTFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAAMDDFAAFVEKCCK ADDKEТСFAEЕGKKLVAASQAALGL 798 - HALB option 12 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 799 - HALB art DAHKSEVAHRFKDLGEENFKALVLIAFA

- 177 041992

option 13 other QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPHLVAASKAALGL 800 - HALB option 14 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST

- 178 041992

PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALGVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 801 - HALB option 15 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 802 - HALB option 16 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP

- 179 041992

KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPHLVAASQAALGL 803 - HALB option 17 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPHLVAASKAALGL 804 - HALB art DAHKSEVAHRFKDLGEENFKALVLIAFA

- 180 041992

option 18 other QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASKAALGL 805 - HALB option 19 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQSPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST

- 181 041992

PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPKLVAASKAALGL 806 - HALB option 20 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGKKLVAASQAALGL 807 - HALB option 21 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP

- 182 041992

KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA GTFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAAMDDFAAFVEKCCK ADDKEТСFAEЕGKKLVAASQAALGL 808 - HALB option 22 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 809 - HALB art DAHKSEVAHRFKDLGEENFKALVLIAFA

- 183 041992

option 23 other QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSIS SKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPHLVAASKAALGL 810 - HALB option 24 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSIS SKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST

- 184 041992

PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALGVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 811 - HALB option 25 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASQAALGL 812 - HALB option 26 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP

- 185 041992

KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPHLVAASQAALGL 813 - HALB option 27 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSWLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPHLVAASKAALGL 814 - HALB art DAHKSEVAHRFKDLGEENFKALVLIAFA

- 186 041992

option 28 other QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALEVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDKFAAFVEKCCK ADDKETCFAEEGPKLVAASKAALGL 815 - HALB option 29 art other DAHKSEVAHRFKDLGEENFKALVLIAFA QYLQQAPFEDHVKLVNEVTEFAKTCVAD ESAENCDKSLHTLFGDKLCTVATLRETY GEMADCCAKQEPERNECFLQHKDDNPNL PRLVRPEVDVMCTAFHDNEETFLKKYLY EIARRHPYFYAPELLFFAKRYKAAFTEC CQAADKAACLLPKLDELRDEGKASSAKQ RLKCASLQKFGERAFKAWAVARLSQRFP KAEFAEVSKLVTDLTKVHTECCHGDLLE CADDRADLAKYICENQDSISSKLKECCE KPLLEKSHCIAEVENDEMPADLPSLAAD FVESKDVCKNYAEAKDVFLGMFLYEYAR RHPDYSVVLLLRLAKTYETTLEKCCAAA DPHECYAKVFDEFKPLVEEPQNLIKQNC ELFEQLGEYKFQNALLVRYTKKVPQVST

- 187 041992

PTLVEVSRNLGKVGSKCCKHPEAKRMPC AEDYLSWLNQLCVLHEKTPVSDRVTKC CTESLVNRRPCFSALDVDETYVPKEFNA ETFTFHADICTLSEKERQIKKQTALVEL VKHKPKATKEQLKAVMDDFAAFVEKCCK ADDKETCFAEEGPKLVAASKAALGL 816 - NS crosste la 1 ASTKGPSVFPLAPSSKSTSGGTAALGCL VKDY FPE PVTVSWNS GAL T S GVHT FPAV LQSSGLYSLSSWTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTP E VT CVWDVS HE D PE VK FNW YVDGVE VH NAKTKPCEEQYGSTYRCVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKG QPREPQVYTLPPSREEMTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYDTTPPV LDSDGSFFLYSDLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK 817 - LC crosste la 1 GQPKAAPSVTLFPPSSEELQANKATLVC LIS D FYPGAVTVAWKADS S PVKAGVE T T TPSKQSNNKYAASSYLSLTPEQWKSHRS YSCQVTHEGSTVEKTVAPTECSDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPCEEQYGSTYRCVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRKEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTT PPVLKSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK 818 - NS crosste la 2 ASTKGPSVFPLAPCSRSTSESTAALGCL VKDY FPE PVTVSWNS GAL T S GVHT FPAV LQSSGLYSLSSWTVPSSNFGTQTYTCN VDHKPSNTKVDKTVEPKSSDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTP

- 188 041992

E VT C VWDVS NOT D RE VK FNW YVDGVE VH NAKTKPREEQYNSTYRWSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKG QPREPQVYTLPPSREEMTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYDTTPPV LDSDGSFFLYSDLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK 819 - LC crosste la 2 GQPKAAPSVTLFPPSSEELQANKATLVC LIS D FYРGAVTVAWKADS S РVKAGVE Т Т TPSKQSNNKYAASSYLSLTPEQWKSHRS YSCQVTHEGSTVEKTVAPTECSEPKSSD KTHTCPPCPAPEAAGGPSVFLFPPKPKD TLMISRTPEVTCVWDVSHEDPEVKFNW YVDGVE VHNAKTKPREEQYNSTYRWSV LTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRKEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLKSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSP GK 820 - binding domain Ec heteroEc DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS 821 - partner Fc hetero- Fc DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE

- 189 041992

NNYDTTPPVLDSDGSFFLYSDLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 822 - target Fc maxi la 1 EPKSSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR KEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLKSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 823 - CD3 Fc max la 1 EPKSSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYDTTPPVLDSDGSFFLYSDLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 824 - target Fc maxi la 2 EPKSSDKTHTCPPCPAPEAAGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNST YRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR KEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLKSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 825 - CD3 Fc max la 2 EPKSSDKTHTCPPCPAPEAAGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNST YRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR

- 190 041992

EEMTKNQVSLTCLVKGFYPSDIAVEVES NGQPENNYDTTPPVLDSDGSFFLYSDLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 826 - Mono Fc APELLGGPSVFLFPPKPKDTLMISRTPE VT VWDVS NOT D RE VK FNW YVDGVE VHN AKTKPREEQYNSTYRWSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVTTLPPSREEMTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYDTTPPVL DSDGSFFLYSDLTVVDKLSCSWKQQGNHE 827 - CDR-L1 F6A art other GSSTGAVTSGYYPN 828 - CDR-L2 F6A art other GTKFLAP 829 - CDR-L3 F6A art other ALWYSNRWV 830 - CDR-H1 F6A art other IYAMN 831 - CDR-H2 F6A art other RIRSKYNNYATYYADSVKS 832 - CDR-H3 F6A art other HGNFGNSYVSFFAY 833 - VH-F6A art other EVQLVESGGGLVQPGGSLKLSCAASGFT ENIYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKSRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYVS HER AYWGQGTLVTVSS 834 - VL-F6A art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 835 - VH-VL F6A art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNIYAMNWVRQAPGKGLEWVARIRSKYN

- 191 041992

NYATYYADSVKSRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYVS HER AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPTVED EAEYYCALWGYSNRWVLG 836 - CDR-L1 H2C art other GSSTGAVTSGYYPN 837 - CDR-L2 H2C art other GTKFLAP 838 - CDR-L3 H2C art other ALWYSNRWV 839 - CDR-H1 H2C art other KYAMN 840 - CDR-H2 H2C art other RIRSKYNNYATYYADSVKD 841 - CDR-H3 H2C art other HGNFGNSYISYWAY 842 - VH H2C art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSS 843 - VL H2C art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 844 - VH-VL H2C art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTTKGA VTSGYYPNFLVQQGKPGQ

- 192 041992

APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 845 - CDR-L1 HIE art other GSSTGAVTSGYYPN 846 - CDR-L2 HIE art other GTKFLAP 847 - CDR-L3 HIE art other ALWYSNRWV 848 - CDR-H1 HIE art other SYAMN 849 - CDR-H2 HIE art other RIRSKYNNYATYYADSVKG 850 - CDR-H3 HIE art other HGNFGNSYLSFWAY 851 - VH HIE art other EVQLVESGGGLEQPGGSLKLSCAASGFT FNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYLS FW AYWGQGTLVTVSS 852 - VL HIE art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 853 - VH-VL HIE art naya EVQLVESGGGLEQPGGSLKLSCAASGFT FNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYLS FW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 854 - CDR-L1 G4H art naya GSSTGAVTSGYYPN 855 - CDR-L2 art GTKFLAP

- 193 041992

G4H other 856 - CDR-L3 G4H art other ALWYSNRWV 857 - CDR-H1 G4H art other RYAMN 858 - CDR-H2 G4H art other RIRSKYNNYATYYADSVKG 859 - CDR-H3 G4H art other HGNFGNSYLSYFAY 860 - VH G4H art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNRYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYLSYF AYWGQGTLVTVSS 861 - VL G4H art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 862 - VH-VL G4H art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNRYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYLSYF AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 863 - CDR-L1 A2 J art other RSSTGAVTSGYYPN 864 - CDR-L2 A2 J art naya ATDMRPS 865 - CDR-L3 A2J art naya ALWYSNRWV 866 - CDR-H1 A2J art naya VYAMN

- 194 041992

867 - CDR-H2 A2J art other RIRSKYNNYATYYADSVKK 868 - CDR-H3 A2 J art other HGNFGNSYLSWWAY 869 - VH A2J art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNVYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKKRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYLSWW AYWGQGTLVTVSS 870 - VL A2J art other QTWTQEPSLTVSPGGTVTLTCRSSTGA VTSGYYPNWVQQKPGQAPRGLIGATDMR PSGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 871 - VH-VL A2J art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNVYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKKRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYLSWW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCRSSTGA VTSGYYPNWVQQKPGQAPRGLIGATDMR PSGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 872 - CDR-L1 EIL art naya GSSTGAVTSGYYPN 873 - CDR-L2 EIL art naya GTKFLAP 874 - CDR-L3 EIL art naya ALWYSNRWV 875 - CDR-H1 EIL art naya KYAMN 876 - CDR-H2 EIL art naya RIRSKYNNYATYYADSVKS 877 - CDR-H3 EIL art naya HGNFGNSYTSYYAY 878 - VH EIL art EVQLVESGGGLVQPGGSLKLSCAASGFT

- 195 041992

other FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKSRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYTSYY AYWGQGTLVTVSS 879 - VL EIL art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 880 - VH-VL EIL art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKSRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYTSYY AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 881 - CDR-L1 E2M art other RSSTGAVTSGYYPN 882 - CDR-L2 E2M art other ATDMRPS 883 - CDR-L3 E2M art other ALWYSNRWV 884 - CDR-H1 E2M art other GYAMN 885 - CDR-H2 E2M art other RIRSKYNNYATYYADSVKE 886 - CDR-H3 E2M art other HRNFGNSYLSWFAY 887 - VH E2M art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNGYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKERFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHRNFGNSYLSWF AYWGQGTLVTVSS 888 - VL E2M art QTWTQEPSLTVSPGGTVTLTCRSSTGA

- 196 041992

other VTSGYYPNWVQQKPGQAPRGLIGATDMR PSGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 889 - VH-VL E2M art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNGYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKERFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHRNFGNSYLSWF AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCRSSTGA VTSGYYPNWVQQKPGQAPRGLIGATDMR PSGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 890 - CDR-L1 F7O art other GSSTGAVTSGYYPN 891 - CDR-L2 F7O art other GTKFLAP 892 - CDR-L3 F7O art other ALWYSNRWV 893 - CDR-H1 F7O art other VYAMN 894 - CDR-H2 F7O art other RIRSKYNNYATYYADSVKK 895 - CDR-H3 F7O art naya HGNFGNSYISWWAY 896 - VH F7O art naya EVQLVESGGGLVQPGGSLKLSCAASGFT FNVYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKKRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISWW AYWGQGTLVTVSS 897 - VL F7O art naya QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWYSNRWVFGGGTKLTVL 898 - VH-VL F7O art naya EVQLVESGGGLVQPGGSLKLSCAASGFT FNVYAMNWVRQAPGKGLEWVARIRSKYN

- 197 041992

NYATYYADSVKKRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISWW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGYYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCALWGYSNRWVLG 899 - CDR-L1 F12Q art other GSSTGAVTSGNYPN 900 - CDR-L2 F12Q art other GTKFLAP 901 - CDR-L3 F12Q art other VLWYSNRWV 902 - CDR-H1 F12Q art other SYAMN 903 - CDR-H2 F12Q art other RIRSKYNNYATYYADSVKG 904 - CDR-H3 F12Q art other HGNFGNSYVSWWAY 905 - VH F12Q art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYVSWW AYWGQGTLVTVSS 906 - VL F12Q art naya QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 907 - VH-VL F12Q art naya EVQLVESGGGLVQPGGSLKLSCAASGFT FNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYVSWW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWRGVQGPGQAP

- 198 041992

APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 908 - CDR-L1 I2C art other GSSTGAVTSGNYPN 909 - CDR-L2 I2C art other GTKFLAP 910 - CDR-L3 I2C art other VLWYSNRWV 911 - CDR-H1 I2C art other KYAMN 912 - CDR-H2 I2C art other RIRSKYNNYATYYADSVKD 913 - CDR-H3 I2C art other HGNFGNSYISYWAY 914 - VH I2C art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSS 915 - VL I2C art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 916 - VH-VL I2C art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 917 - VH F12q art other EVQLVESGGGLVQPGGSLKLSCAASGFT FNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ

- 199 041992

MNSLKTEDTAVYYCVRHGNFGNSYVSWW AYWGQGTLVTVSS 918 - VL F12q art other QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 919 - VH-VL F12q art other EVQLVESGGGLVQPGGSLRLSCAASGFT FNSYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKGRFTISRDDSKNTAYLQ MNSLKTEDTAVYYCVRHGNFGNSYVSWW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 920 CD70- 13_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSS 921 CD70- 13_CC VL EIVLTQSPGTLSLSPGEGATLSCRAGQS VRSSYLGWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPPTFGCGTKLEIK 922 CD70- 13_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTKLEIK

- 200 041992

923 CD70- 13_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYADSVKGRFTISRDNSRNTLYLQMN SLRDEDTAVYYCARVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVL 924 CD70- 14_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGRCLEWVSAISGSGG STFYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 925 CD70- 14_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQRPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTRLEIR 926 CD70- 14_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGRCLEWVSAISGSGG STFYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRTTFYFD

- 201 041992

QQYGDLPFTFGCGTKLEIK 927 CD70- 14_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLKLSCAASGFT ESIYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 928 CD70- 15_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 929 CD70- 15_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKLEIK 930 CD70- 15_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRAPD

- 202 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIK 931 CD70- 15_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 932 CD70- 16_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 933 CD70- 16_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSSYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKLEIK 934 CD70- 16_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY

- 203 041992

LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIK 935 CD70- 16_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 936 CD70- 17_CC vh EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RTHYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 937 CD70- 17_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQRPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTRLEIR 938 CD70- 17_CC scFv EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG RTHYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 204 041992

QSPGTLSLSPGERAATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIK 939 CD70- 17_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 940 CD70- 18_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 941 CD70- 18_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYDAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTTFGCGTKLEIK 942 CD70- 18_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 205 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERAATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSPPTFGCGTKLEIK 943 CD70- 18_CCxI 2C bispecificity chesky molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 944 CD70- 19_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 945 CD70- 19_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKLEIK 946 CD70- 19_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN

- 206 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIK 947 CD70- 19_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 948 CD70- 21_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVS 949 CD70- 21_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGCGTKLEIK 950 CD70- 21_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG

- 207 041992

RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKLEIK 951 CD70- 21_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 952 CD70- 22_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 953 CD70- 22_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK 954 CD70- scFv EVQLLESGGGLVQPGGSLRLSCAASGFT

- 208 041992

22_CC FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGGCTDPFGLTISRLEPEDFAVYC QSPGTLSLSPGERATLSCRASQSVRSNY 955 CD70- 22_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 956 CD70- 24_CC vh EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSS 957 CD70- 24_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK

- 209 041992

958 CD70- 24_CC scFv EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG STFYADSVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 959 CD70- 24_CCxI 2C bispecificity molecular molecule EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVL 960 CD70- 25_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 961 CD70- 25_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQRPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF

- 210 041992

AVYYCQQYGDLPFTFGCGTKVEIK 962 CD70- 25_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 963 CD70- 25_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 964 CD70- 26_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 965 CD70- 26_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA

- 211 041992

TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKVEIK 966 CD70- 26_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIK 967 CD70- 26_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 968 CD70_lG2 vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 969 CD70_l- VL EIVLTQSPGTLSLSPGERATLSCRASQS

- 212 041992

G2 VRGNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPFTFGPGTKVEIK 970 CD70_lG2 scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIK 971 CD70_lG2xI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 972 CD70_l- G2_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS

- 213 041992

973 CD70_l- G2_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRGNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPFTFGCGTKVEIK 974 CD70_l- G2_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIK 975 CD70_l- G2_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 976 CD70- 27_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 214 041992

GTLVTVSS 977 CD70- 27_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKVEIK 978 CD70- 27_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIK 979 CD70- 27_CCxI 2C bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 980 CD70- 28_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN

- 215 041992

SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 981 CD70- 28_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGASNRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGISPPTFGCGTKVEIK 982 CD70- 28_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTKVEIK 983 CD70- 28_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 984 CD70- 31_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG

- 216 041992

RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 985 CD70- 31_CC VL EIVLTQSPATLSVSPGERATLSCRASQS VS SNLAWYQQKPGQAPRLLIYGS S SRAT GIPDRFSGSGSGTDFTLTISRLEPEDFA VYYCQQYGSSPPPFGCGTKVEIK 986 CD70- 31_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIK 987 CD70- 31_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 988 CD70- vh EVQLLESGGGMVQPGGSLRLSCAASGFT

- 217 041992

32_CC FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 989 CD70- 32_CC VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSDYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYHCQQYGSTPPTFGCGTKVEIK 990 CD70- 32_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTKVEIK 991 CD70- 32_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL

- 218 041992

992 CD70- 37_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKCLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 993 CD70- 37_CC VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSSYFAWYQQKPGQAPRLLIYGASTRA TGIPARFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPTFGCGTKVEIK 994 CD70- 37_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKCLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIK 995 CD70- 37_CCxI 2C bispecificity chesky molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKCLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 219 041992

YYCVLWYSNRWVFGGGTKLTVL 996 CD70- 3 8_CC vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 997 CD70- 3 8_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPPSFGCGTKVEIK 998 CD70- 3 8_CC scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIK 999 CD70- 38_CCxI 2C bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG

- 220 041992

TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1000 CD70- 3 9_CC vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSS 1001 CD70- 3 9_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGCGTKVEIK 1002 CD70- 3 9_CC scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKVEIK 1003 CD70- 39_CCxI 2C bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 221 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1004 CD70- 41_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 1005 CD70- 41_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVDIK 1006 CD70- 41_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIK 1007 CD70- 41_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 222 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1008 CD70- 42_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1009 CD70- 42_CC VL EIVLTQSPGTLSLSPGERATLSCRASQG VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTTFGCGTKVDIK 1010 CD70- 42_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIK 1011 CD70- 42_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW

- 223 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1012 CD70- 4 3_CC vh EVQLLESGGGWQPGRSLRLSCAASGFT FS SYAMSWVRQAPGKCLEWVSAIS GS GG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1013 CD70- 4 3_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQRPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSPPPTTFGCGTRVDIR 1014 CD70- 4 3_CC scFv EVQLLESGGGWQPGRSLRLSCAASGFT FS SYAMSWVRQAPGRCLEWVSAIS GS GG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTRVDIR 1015 CD70- 43_CCxI 2C bispecific molecule EVQLLESGGGWQPGRSLRLSCAASGFT FS SYAMSWVRQAPGRCLEWVSAIS GS GG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN

- 224 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1016 CD70- 48_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 1017 CD70- 48_CC VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASILQS GVPSKFSGSGSGTDFTLTISSLQPEDFA IYYCQQYFAYPITFGCGTRLEIK 1018 CD70- 48_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIK 1019 CD70- 48_CCxI 2C bispecificity chesky molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT

- 225 041992

YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGL 1020 CD70- 53_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1021 CD70- 53_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTTFGCGTRLEIK 1022 CD70- 53_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIK 1023 CD70- 53_CCxI 2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 226 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQDEKPGQAPRGLIGGTKFLAPTKGLWGGPEALTLSGVQQGTLVTVSSGGGGSGGGGSGGGGSQTV 1024 CD70- 54_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1025 CD70- 54_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYVAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTRLEIK 1026 CD70- 54_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIK 1027 CD70- 54_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIKSGGGGSEVQ

- 227 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1028 CD70- 58_CC vh QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSS 1029 CD70- 58_CC VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIK 1030 CD70- 58_CC scFv QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIK 1031 CD70- 58_CCxI 2C bispecificity chesky molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA

- 228 041992

TYYCQQSFSSPRTFGCGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVL 1032 CD70- 62_CC vh EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSS 1033 CD70- 62_CC VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASTLQS GVPSRFSGSGSGTDFTLTISSLQAEDVA VYYCQQYYSTPLTFGCGTKVEIK 1034 CD70- 62_CC scFv EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIK 1035 CD70- 62_CCxI 2C bispecificity molecular molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPQLSGLIYA

- 229 041992

FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1036 CD70- 2 3_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSS 1037 CD70- 2 3_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK 1038 CD70- 2 3_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 1039 CD70- 23_CCxI 2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY

- 230 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1040 CD70- 55_CC vh QVQLVE S GGGWQPGRS LRL S CAAS G FM 1041 CD70- 55_CC VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGRGSGTDFTLTISSLQPEDFA TYYCQQSYSTPFTFGCGTKVEIK 1042 CD70- 55_CC scFv QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKCLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIK 1043 CD70- 55_CCxI 2C bispecific molecule QVQLVE S GGGWQPGRS LRL S CAAS G FM

- 231 041992

IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 1044 CD70- 13D VH CDR1 SYAMS 1045 CD70- 13D VH CDR2 VISGSGGRPNYAESVKG 1046 CD70- 13D VH CDR3 VDYSNYLFFDY 1047 CD70- 13D VL CDR1 RAGQSVRSSYLG 1048 CD70- 13D VL CDR2 GASS RAT 1049 CD70- 13D VL CDR3 QQYGYSPPT 1050 CD70- 13D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSS 1051 CD70- 13D_CC VL EIVLTQSPGTLSLSPGEGATLSCRAGQS VRSSYLGWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPPTFGCGTKLEIK

- 232 041992

1052 CD70- 13D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTKLEIK 1053 CD70- 13D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1054 CD70- 13D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSS 1055 CD70- 13D VL EIVLTQSPGTLSLSPGEGATLSCRAGQS VRSSYLGWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF

- 233 041992

AVYYCQQYGYSPPTFGGGTKLEIK 1056 CD70- 13D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIK 1057 CD70- 13DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1058 CD70- 14D VH CDR1 I YAMS 1059 CD70- 14D VH CDR2 AISGSGGSTFYAESVKG 1060 CD70- 14D VH CDR3 HDYSNYPYFDY 1061 CD70- VL CDR1 RASQSVRSSYLA

- 234 041992

14D 1062 CD70- 14D VL CDR2 GASS RAT 1063 CD70- 14D VL CDR3 QQYGDLPFT 1064 CD70- 14D_CC vh EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1065 CD70- 14D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKLEIK 1066 CD70- 14D_CC scFv EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIK 1067 CD70- 14D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 235 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1068 CD70- 14D vh EVQLLESGGGLVQPGGSLKLSCAASGFT ESIYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1069 CD70- 14D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKLEIK 1070 CD70- 14D scFv EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIK 1071 CD70- 14DxI2C bispecificity chesky molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 236 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGG 1072 CD70_61 -DID VH CDR1 SYAMS 1073 CD70_61 -DID VH CDR2 AISGSGGRT FYAE SVE G 1074 CD70_61 -DID VH CDR3 HDYSNYPYFDY 1075 CD70_61 -DID VL CDR1 RASQSVRSSYLA 1076 CD70_61 -DID VL CDR2 GASS RAT 1077 CD70_61 -DID VL CDR3 QQYGSSPFT 1078 CD70_61 -D1D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1079 CD70_61 -D1D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKLEIK 1080 CD70_61 -D1D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD

- 237 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIK 1081 CD70_61 DlD_CCx I2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1082 CD70_61 -DID vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1083 CD70_61 -DID VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKLEIK 1084 CD70_61 -DID scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY

- 238 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIK 1085 CD70_61 DlDxI2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1086 CD70- 16D VH CDR1 SYAMS 1087 CD70- 16D VH CDR2 AISGSGGRT FYAE SVE G 1088 CD70- 16D VH CDR3 HDYSNYPYFDY 1089 CD70- 16D VL CDR1 RASQSIRSSYLA 1090 CD70- 16D VL CDR2 GASS RAT 1091 CD70- 16D VL CDR3 QQYGDLPFT 1092 CD70- 16D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG

- 239 041992

RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1093 CD70- 16D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSSYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKLEIK 1094 CD70- 16D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIK 1095 CD70- 16D_CCx I2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1096 CD70- vh EVQLLESGGGMVQPGGSLRLSCAASGFT

- 240 041992

16D FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1097 CD70- 16D VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSSYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKLEIK 1098 CD70- 16D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIK 1099 CD70- 16DxI2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL

- 241 041992

1100 CD70- 17D VH CDR1 SYAMS 1101 CD70- 17D VH CDR2 AISGSGGRTHYAESVKG 1102 CD70- 17D VH CDR3 HDYSNYPYFDY 1103 CD70- 17D VL CDR1 RASQSVRSSYLA 1104 CD70- 17D VL CDR2 GASS RAT 1105 CD70- 17D VL CDR3 QQYGSSPFT 1106 CD70- 17D_CC vh EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1107 CD70- 17D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKLEIK 1108 CD70- 17D_CC scFv EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIK 1109 CD70- 17D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 242 041992

QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1110 CD70- 17D vh EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1111 CD70- 17D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKLEIK 1112 CD70- 17D scFv EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIK 1113 CD70- 17DxI2C bispecificity molecular molecule EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 243 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1114 CD70- 18D VH CDR1 SYAMS 1115 CD70- 18D VH CDR2 LISGSGGRTHYAESVKG 1116 CD70- 18D VH CDR3 HDYSNYPYFDY 1117 CD70- 18D VL CDR1 RASQSVRSTYLA 1118 CD70- 18D VL CDR2 DASS RAT 1119 CD70- 18D VL CDR3 QQYGSSPPT 1120 CD70- 18D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1121 CD70- 18D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYDAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTTFGCGTKLEIK

- 244 041992

1122 CD70- 18D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIR 1123 CD70- 18D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSLISGSGG RTHYAESVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVL 1124 CD70- 18D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSLISGSGG RTHYAESVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1125 CD70- 18D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQRPGQAPRLLIYDAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF

- 245 041992

AVYFCQQYGSSPPTFGGGTKLEIK 1126 CD70- 18D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSLIS GS GG RTHYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTKLEIK 1127 CD70- 18DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSLIS GS GG RTHYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVL 1128 CD70- 19D VH CDR1 TYAMS 1129 CD70- 19D VH CDR2 AISGSGGSTFYAESVRG ISO CD70- 19D VH CDR3 HDYSNYPYFDY 1131 CD70- VL CDR1 RASQSVRSSYLA

- 246 041992

19D 1132 CD70- 19D VL CDR2 GASS RAT 1133 CD70- 19D VL CDR3 QQYGDLPFT 1134 CD70- 19D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1135 CD70- 19D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKLEIK 1136 CD70- 19D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIK 1137 CD70- 19D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 247 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1138 CD70- 19D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1139 CD70- 19D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKLEIK 1140 CD70- 19D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIK 1141 CD70- 19DxI2C bispecificity chesky molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 248 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGG 1142 CD70- 21D VH CDR1 TYAMS 1143 CD70- 21D VH CDR2 AISGSGGRT FYAE SVE G 1144 CD70- 21D VH CDR3 HDYSNYPYFDY 1145 CD70- 21D VL CDR1 RASQSVRSTYLA 1146 CD70- 21D VL CDR2 GASS RAT 1147 CD70- 21D VL CDR3 QQYGDLPFT 1148 CD70- 21D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1149 CD70- 21D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGCGTKLEIK 1150 CD70- 21D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRAD

- 249 041992

RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKLEIK 1151 CD70- 21D_CCx I2C bispecificity chesky molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1152 CD70- 21D vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1153 CD70- 21D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS TYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGPGTKLEIK 1154 CD70- 21D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY

- 250 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIK 1155 CD70- 21DxI2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1156 CD70- 22D VH CDR1 SYAMS 1157 CD70- 22D VH CDR2 AISGSGGYTYYAESVKG 1158 CD70- 22D VH CDR3 HDYSNYPYFDY 1159 CD70- 22D VL CDR1 RASQSVRSNYLA 1160 CD70- 22D VL CDR2 GASS RAT 1161 CD70- 22D VL CDR3 QQYGDLPFT 1162 CD70- 22D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG

- 251 041992

YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1163 CD70- 22D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK 1164 CD70- 22D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 1165 CD70- 22D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1166 CD70- vh EVQLLESGGGLVQPGGSLRLSCAASGFT

- 252 041992

22D FS SYAMSWVRQAPGKGLEWVSAIS GS GG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1167 CD70- 22D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 1168 CD70- 22D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIS GS GG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 1169 CD70- 22DxI2C bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIS GS GG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL

- 253 041992

1170 CD70- 24D VH CDR1 SYAMS 1171 CD70- 24D VH CDR2 AISGSGGSTFYAESVKG 1172 CD70- 24D VH CDR3 HDYSNYPYFDY 1173 CD70- 24D VL CDR1 RASQSVRSSYLA 1174 CD70- 24D VL CDR2 GASS RAT 1175 CD70- 24D VL CDR3 QQYGDLPFT 1176 CD70- 24D_CC vh EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSS 1177 CD70- 24D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK 1178 CD70- 24D_CC scFv EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 1179 CD70- 24D_CCx I2C bispecific molecule EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 254 041992

QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1180 CD70- 24D vh EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSS 1181 CD70- 24D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 1182 CD70- 24D scFv EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 1183 CD70- 24DxI2C bispecificity molecular molecule EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ

- 255 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1184 CD70- 25D VH CDR1 SYAMS 1185 CD70- 25D VH CDR2 AISGSGGRT FYAE SVE G 1186 CD70- 25D VH CDR3 HDYSNYPYFDY 1187 CD70- 25D VL CDR1 RASQSVRSNYLA 1188 CD70- 25D VL CDR2 GASS RAT 1189 CD70- 25D VL CDR3 QQYGDLPFT 1190 CD70- 25D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1191 CD70- 25D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK

- 256 041992

1192 CD70- 25D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 1193 CD70- 25D_CCx I2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1194 CD70- 25D vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1195 CD70- 25D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF

- 257 041992

AVYYCQQYGDLPFTFGPGTKVEIK 1196 CD70- 25D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVEIR 1197 CD70- 25DxI2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVL 1198 CD70- 26D VH CDR1 SYAMS 1199 CD70- 26D VH CDR2 AISGSGGRT FYAE SVE G 1200 CD70- 26D VH CDR3 HDYSNYPYFDY 1201 CD70- VL CDR1 RASQSVRSSYLA

- 258 041992

26D 1202 CD70- 26D VL CDR2 GASS RAT 1203 CD70- 26D VL CDR3 QQYGSSPFT 1204 CD70- 26D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1205 CD70- 26D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKVEIK 1206 CD70- 26D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIK 1207 CD70- 26D_CCx I2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 259 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1208 CD70- 26D vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1209 CD70- 26D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKVEIK 1210 CD70- 26D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIK 1211 CD70- 26DxI2C bispecificity chesky molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 260 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGG 1212 CD70_lG2D VH CDR1 SYAMS 1213 CD70_lG2D VH CDR2 AISGSGGSTFYAESVQG 1214 CD70_lG2D VH CDR3 HDYSNYPYFDY 1215 CD70_lG2D VL CDR1 RASQSVRGNYLA 1216 CD70_lG2D VL CDR2 GASS RAT 1217 CD70_lG2D VL CDR3 QQYGYSPFT 1218 CD70_l- G2D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1219 CD70_l- G2D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRGNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPFTFGCGTKVEIK 1220 CD70_l- G2D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD

- 261 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIK 1221 CD70_l- G2D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1222 CD70_lG2D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1223 CD70_lG2D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRGNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGYSPFTFGPGTKVEIK 1224 CD70_lG2D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY

- 262 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIK 1225 CD70_lG2DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1226 CD70- 27D VH CDR1 TYAMS 1227 CD70- 27D VH CDR2 AISGSGGGTFYAESVKG 1228 CD70- 27D VH CDR3 HDYSNYPYFDY 1229 CD70- 27D VL CDR1 RASQSIRSNYLA 1230 CD70- 27D VL CDR2 GASS RAT 1231 CD70- 27D VL CDR3 QQYGSSPFT 1232 CD70- 27D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG

- 263 041992

GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1233 CD70- 27D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGCGTKVEIK 1234 CD70- 27D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIK 1235 CD70- 27D_CCx I2C bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1236 CD70- vh EVQLLESGGGLVQPGGSLRLSCAASGFT

- 264 041992

27D FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1237 CD70- 27D VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPFTFGPGTKVEIK 1238 CD70- 27D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIK 1239 CD70- 27DXI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL

- 265 041992

1240 CD70- 28D VH CDR1 TYAMS 1241 CD70- 28D VH CDR2 LISGSGGRTYYAESVKG 1242 CD70- 28D VH CDR3 HDYSNYPYFDY 1243 CD70- 28D VL CDR1 RASQSVRSNYLA 1244 CD70- 28D VL CDR2 GASNRAT 1245 CD70- 28D VL CDR3 QQYGISPPT 1246 CD70- 28D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1247 CD70- 28D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQRPGQAPRLLIYGASNRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGISPPTFGCGTRVEIR 1248 CD70- 28D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGRCLEWVSLISGSGG RTYYAESVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTRVEIR 1249 CD70- 28D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGRCLEWVSLISGSGG RTYYAESVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 266 041992

QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1250 CD70- 28D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1251 CD70- 28D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGASNRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGISPPTFGGGTKVEIK 1252 CD70- 28D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIK 1253 CD70- 28DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 267 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1254 CD70- 31D VH CDR1 SYAMS 1255 CD70- 31D VH CDR2 AIS GS GGRAQYAE SVQG 1256 CD70- 31D VH CDR3 HDYSNYPYFDY 1257 CD70- 31D VL CDR1 RASQSVSSNLA 1258 CD70- 31D VL CDR2 GSSSRAT 1259 CD70- 31D VL CDR3 QQYGSSPPP 1260 CD70- 31D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1261 CD70- 31D_CC VL EIVLTQSPATLSVSPGERATLSCRASQS VS SNLAWYQQKPGQAPRLLIYGS S SRAT GIPDRFSGSGSGTDFTLTISRLEPEDFA VYYCQQYGSSPPPFGCGTKVEIK

- 268 041992

1262 CD70- 31D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIK 1263 CD70- 31D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1264 CD70- 31D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1265 CD70- 31D VL EIVLTQSPATLSVSPGERATLSCRASQS VS SNLAWYQQKPGQAPRLLIYGS S SRAT GIPDRFSGSGSGTDFTLTISRLEPEDFA

- 269 041992

VYYCQQYGSSPPPFGGGTKVEIK 1266 CD70- 31D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIK 1267 CD70- 31DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1268 CD70- 32D VH CDR1 SYAMS 1269 CD70- 32D VH CDR2 AISGSGGRT FYAE SVE G 1270 CD70- 32D VH CDR3 HDYSNYPYFDY 1271 CD70- VL CDR1 RASQGVRSDYLA

- 270 041992

32D 1272 CD70- 32D VL CDR2 GASSRAT 1273 CD70- 32D VL CDR3 QQYGSTPPT 1274 CD70- 32D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSS 1275 CD70- 32D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSDYLAWYQQRPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYHCQQYGSTPTFGCGTRVEIR 1276 CD70- 32D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTRVEIR 1277 CD70- 32D_CCx I2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN

- 271 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1278 CD70- 32D vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 1279 CD70- 32D VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSDYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYHCQQYGSTPPTFGGGTKVEIK 1280 CD70- 32D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIK 1281 CD70- 32DxI2C bispecific molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 272 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGG 1282 CD70- 37D VH CDR1 SYAMS 1283 CD70- 37D VH CDR2 AIGEGGGYTYYAESVKG 1284 CD70- 37D VH CDR3 HDYSNYPYFDY 1285 CD70- 37D VL CDR1 RASQGVRSSYFA 1286 CD70- 37D VL CDR2 GAST RAT 1287 CD70- 37D VL CDR3 QQYGSSPPT 1288 CD70- 37D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVS 1289 CD70- 37D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSSYFAWYQQKPGQAPRLLIYGASTRA TGIPARFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPTFGCGTKVEIK 1290 CD70- 37D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA

- 273 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSPPTFGCGTKVEIK 1291 CD70- 37D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1292 CD70- 37D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1293 CD70- 37D VL EIVLTQSPGTLSLSPGERATLSCRASQG VRSSYFAWYQQKPGQAPRLLIYGASTRA TGIPARFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSPPTFGQGTKVEIK 1294 CD70- 37D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY

- 274 041992

FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSPPTFGQGTKVEIK 1295 CD70- 37DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1296 CD70- 38D VH CDR1 SYAMS 1297 CD70- 38D VH CDR2 AISGSGGRT FYAE SVE G 1298 CD70- 38D VH CDR3 HDYSNYPYFDY 1299 CD70- 38D VL CDR1 RASQSIRSNYLA 1300 CD70- 38D VL CDR2 GASS RAT 1301 CD70- 38D VL CDR3 QQYGSSPPS 1302 CD70- 38D_CC vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG

- 275 041992

RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1303 CD70- 38D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQKPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPPSFGCGTKVEIK 1304 CD70- 38D_CC scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIK 1305 CD70- 38D_CCx I2C bispecific molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1306 CD70- vh EVQLLESGGGWQPGRSLRLSCAASGFT

- 276 041992

38D FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1307 CD70- 38D VL EIVLTQSPGTLSLSPGERATLSCRASQS IRSNYLAWYQQRPGQAPRLLIYGASSRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGSSPPSFGQGTRVEIR 1308 CD70- 38D scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTRVEIR 1309 CD70- 38DxI2C bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVL

- 277 041992

1310 CD70- 39D VH CDR1 SYAMS 1311 CD70- 39D VH CDR2 AISGSGGGTFYAESVEG 1312 CD70- 39D VH CDR3 HDYSNYPYFDY 1313 CD70- 39D VL CDR1 RASQSVRSSYLA 1314 CD70- 39D VL CDR2 GASS RAT 1315 CD70- 39D VL CDR3 QQYGDLPFT 1316 CD70- 39D_CC vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSS 1317 CD70- 39D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGCGTKVEIK 1318 CD70- 39D_CC scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTRVEIR 1319 CD70- 39D_CCx I2C bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSAISGSGG GT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 278 041992

QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1320 CD70- 39D vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSS 1321 CD70- 39D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYSCQQYGDLPFTFGPGTKVEIK 1322 CD70- 39D scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIK 1323 CD70- 39DxI2C bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL

- 279 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1324 CD70- 41D VH CDR1 SYAMS 1325 CD70- 41D VH CDR2 AISGSGGRT FYAE SVE G 1326 CD70- 41D VH CDR3 HDYSNYPYFDY 1327 CD70- 41D VL CDR1 RASQSVRSSYLA 1328 CD70- 41D VL CDR2 GASS RAT 1329 CD70- 41D VL CDR3 QQYGDLPFT 1330 CD70- 41D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 1331 CD70- 41D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVDIK

- 280 041992

1332 CD70- 41D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIK 1333 CD70- 41D_CCx I2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1334 CD70- 41D vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSS 1335 CD70- 41D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF

- 281 041992

AVYYCQQYGDLPFTFGPGTKVDIK 1336 CD70- 41D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVDIK 1337 CD70- 41DxI2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1338 CD70- 42D VH CDR1 TYAMS 1339 CD70- 42D VH CDR2 LISGSGGRTYYAESVKG 1340 CD70- 42D VH CDR3 HDYSNYPYFDY 1341 CD70- VL CDR1 RASQGVRSSYLA

- 282 041992

42D 1342 CD70- 42D VL CDR2 GASS RAT 1343 CD70- 42D VL CDR3 QQYGSSPPT 1344 CD70- 42D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1345 CD70- 42D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQG VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTTFGCGTKVDIK 1346 CD70- 42D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIK 1347 CD70- 42D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 283 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1348 CD70- 42D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1349 CD70- 42D VL EIVLTQSPGTLSLSPGERATLSCRASQG VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTFGGGTKVDIK 1350 CD70- 42D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIK 1351 CD70- 42DxI2C bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 284 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGG 1352 CD70- 43D VH CDR1 SYAMS 1353 CD70- 43D VH CDR2 AISGSGGRT FYAE SVE G 1354 CD70- 43D VH CDR3 HDYSNYPYFDY 1355 CD70- 43D VL CDR1 RASQSVRSNYLA 1356 CD70- 43D VL CDR2 GASS RAT 1357 CD70- 43D VL CDR3 QQYGSSPPT 1358 CD70- 43D_CC vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1359 CD70- 43D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTTFGCGTKVDIK 1360 CD70- 43D_CC scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRAD

- 285 041992

RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSPPTFGCGTKVDIK 1361 CD70- 43D_CCx I2C bispecificity chesky molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1362 CD70- 43D vh EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1363 CD70- 43D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRSNYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTINRLEPEDF AVYYCQQYGSSPPTFGGGTKVDIK 1364 CD70- 43D scFv EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY

- 286 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSPPTFGGGTKVDIK 1365 CD70- 43DxI2C bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1366 CD70- 48D VH CDR1 SYAMS 1367 CD70- 48D VH CDR2 VISGSGGITDFAESVKG 1368 CD70- 48D VH CDR3 HDYSNYFFFDY 1369 CD70- 48D VL CDR1 RASQGISNYLA 1370 CD70- 48D VL CDR2 AASILQS 1371 CD70- 48D VL CDR3 QQYFAYPIT 1372 CD70- 48D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG

- 287 041992

ITDFAESVKGRFTISRDNSSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 1373 CD70- 48D_CC VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASILQS GVPSKFSGSGSGTDFTLTISSLQPEDFA IYYCQQYFAYPITFGCGTRLEIK 1374 CD70- 48D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFATYYCQ QYFAYPITFGCGTRLEIK 1375 CD70- 48D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1376 CD70- vh EVQLLESGGGLVQPGGSLRLSCAASGFT

- 288 041992

48D FSSYAMSWVRQAPGKGLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSS 1377 CD70- 48D VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASILQS GVPSKFSGSGSGTDFTLTISSLQPEDFA IYYCQQYFAYPITFGQGTRLEIK 1378 CD70- 48D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIK 1379 CD70- 48DxI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL

- 289 041992

1380 CD70- 53D VH CDR1 SYAMS 1381 CD70- 53D VH CDR2 AISGSGGRT FYAE SVE G 1382 CD70- 53D VH CDR3 HDYSNYPYFDY 1383 CD70- 53D VL CDR1 RASQSVRSSYLA 1384 CD70- 53D VL CDR2 GASS RAT 1385 CD70- 53D VL CDR3 QQYGSSPPT 1386 CD70- 53D_CC vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1387 CD70- 53D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTTFGCGTRLEIK 1388 CD70- 53D_CC scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIK 1389 CD70- 53D_CCx I2C bispecific molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 290 041992

QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1390 CD70- 53D vh EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSS 1391 CD70- 53D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQRPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYFCQQYGSSPPTFGGGTRLEIR 1392 CD70- 53D scFv EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIR 1393 CD70- 53DxI2C bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ

- 291 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1394 CD70- 54D VH CDR1 I YAMS 1395 CD70- 54D VH CDR2 AIGGSGGSTFYAESVKG 1396 CD70- 54D VH CDR3 HDYSNYPYFDY 1397 CD70- 54D VL CDR1 RASQSVRSSYVA 1398 CD70- 54D VL CDR2 GASS RAT 1399 CD70- 54D VL CDR3 QQYGDLPFT 1400 CD70- 54D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1401 CD70- 54D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYVAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTRLEIK

- 292 041992

1402 CD70- 54D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIK 1403 CD70- 54D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT ESIYAMSWVRQAPGKCLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1404 CD70- 54D vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSS 1405 CD70- 54D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYVAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF

- 293 041992

AVYYCQQYGDLPFTFGPGTRLEIK 1406 CD70- 54D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIK 1407 CD70- 54DxI2C bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1408 CD70- 58D VH CDR1 SSSYYWG 1409 CD70- 58D VH CDR2 SIYHSGGTYFNPSLKS 1410 CD70- 58D VH CDR3 HYEILTGYYPDVFDI 1411 CD70- VL CDR1 RASQSISSYLN

- 294 041992

58D 1412 CD70- 58D VL CDR2 AASNLQS 1413 CD70- 58D VL CDR3 QQSFSSPRT 1414 CD70- 58D_CC vh QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSS 1415 CD70- 58D_CC VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIK 1416 CD70- 58D_CC scFv QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIK 1417 CD70- 58D_CCx I2C bispecific molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL

- 295 041992

QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVL 1418 CD70- 58D vh QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSS 1419 CD70- 58D VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIK 1420 CD70- 58D scFv QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIK 1421 CD70- 58DxI2C bispecific molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY

- 296 041992

NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGGSLLGGKAALTLSGTKVQPE DEAEYYCVLWYSNRWVLG 1422 CD70- 62D VH CDR1 SYSMN 1423 CD70- 62D VH CDR2 YISSSGGYIYYAE SVKG 1424 CD70- 62D VH CDR3 GDYSNYAYFDY 1425 CD70- 62D VL CDR1 RASQGISNYLA 1426 CD70- 62D VL CDR2 AASTLQS 1427 CD70- 62D VL CDR3 QQYYSTPLT 1428 CD70- 62D_CC vh EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSS 1429 CD70- 62D_CC VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASTLQS GVPSRFSGSGSGTDFTLTISSLQAEDVA VYYCQQYYSTPLTFGCGTKVEIK 1430 CD70- 62D_CC scFv EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISVPNYL AWYQQKPGAKVPQLSGLIY

- 297 041992

FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIK 1431 CD70- 62D_CCx I2C bispecific molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1432 CD70- 62D vh EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSS 1433 CD70- 62D VL DIQMTQSPSSLSASVGDRVTITCRASQG ISNYLAWYQQKPGKVPKLLIYAASTLQS GVPSRFSGSGSGTDFTLTISSLQAEDVA VYYCQQYYSTPLTFGGGTKVEIK 1434 CD70- 62D scFv EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL

- 298 041992

AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIK 1435 CD70- 62DxI2C bispecificity molecular molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1436 CD70- 23D VH CDR1 VYAMS 1437 CD70- 23D VH CDR2 TISGSGGSTFYAESVKG 1438 CD70- 23D VH CDR3 HDYSNYAYFDY 1439 CD70- 23D VL CDR1 RASQSVRSSYLA 1440 CD70- 23D VL CDR2 GASS RAT 1441 CD70- 23D VL CDR3 QQYGDLPFT 1442 CD70- 23D_CC vh EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISGSGG

- 299 041992

STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSS 1443 CD70- 23D_CC VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGCGTKVEIK 1444 CD70- 23D_CC scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIK 1445 CD70- 23D_CCx I2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1446 CD70- vh EVQLLESGGGLVQPGGSLRLSCAASGFT

- 300 041992

23D FSVYAMSWVRQAPGKGLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSS 1447 CD70- 23D VL EIVLTQSPGTLSLSPGERATLSCRASQS VRS SYLAWYQQKPGQAPRLLIYGAS SRA TGIPDRFSGSGSGTDFTLTISRLEPEDF AVYYCQQYGDLPFTFGPGTKVEIK 1448 CD70- 23D scFv EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIK 1449 CD70- 23DXI2C bispecificity molecular molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL

- 301 041992

1450 CD70- 55D VH CDR1 SYGMH 1451 CD70- 55D VH CDR2 VISYEGSNKYYAESVKG 1452 CD70- 55D VH CDR3 GRYYGSGNYNHGMDV 1453 CD70- 55D VL CDR1 RASQSISSYLN 1454 CD70- 55D VL CDR2 AASSLQS 1455 CD70- 55D VL CDR3 QQSYSTPFT 1456 CD70- 55D_CC vh QVQLVE S GGGWQPGRS LRL S CAAS G FM 1457 CD70- 55D_CC VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGRGSGTDFTLTISSLQPEDFA TYYCQQSYSTPFTFGCGTKVEIK 1458 CD70- 55D_CC scFv QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKCLEWVAVISYEGS NKYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIK 1459 CD70- 55D_CCx I2C bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FM

- 302 041992

IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 1460 CD70- 55D vh QVQLVE S GGGWQPGRS LRL S CAAS G FM 1461 CD70- 55D VL DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASSLQS GVPSRFSGRGSGTDFTLTISSLQPEDFA TYYCQQSYSTPFTFGPGTKVEIK 1462 CD70- 55D scFv QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYEGS NKYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIK 1463 CD70- 55DxI2C bispecificity molecular molecule FSSYGMHWVRQAPGKGLEWVAVISYEGS NKYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD

- 303 041992

VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 1464 CD70- 3.001 VH CDR1 SYGMH 1465 CD70- 3.001 VH CDR2 VTWYDASNKYYGDAVKG 1466 CD70- 3.001 VH CDR3 DLLRGVKGYAMDV 1467 CD70- 3.001 VL CDR1 RASQSLRRIYLA 1468 CD70- 3.001 VL CDR2 DVFDRAT 1469 CD70- 3.001 VL CDR3 QQYSESPFT 1470 CD703.001_C C vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSS 1471 CD70- 3.001_C WITH VL EIVLTQSPGTLSLSPGERATLSCRASQS LRRIYLAWYQQKPGQAPRLLIYDVFDRA TGIPDRFSGGGSGTDFTLTISRLEPEDF

- 304 041992

AVYYCQQYSESPFTFGCGTKVDIK 1472 CD70- 3.001_C WITH scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGCGTKVDIK 1473 CD70- 3.001_C CxI2C bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGCGTKVDIKSGGGGSE VQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNN YATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTKLTVL 1474 CD70- 3.001 vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSS 1475 CD70- 3.001 VL EIVLTQSPGTLSLSPGERATLSCRASQS LRRIYLAWYQQKPGQAPRLLIYDVFDRA

- 305 041992

TGIPDRSGGGSGTDFTLTISRLEPEDF AVYYCQQYSESPFTFGPGTKVDIK 1476 CD70- 3.001 scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDLLRGVRGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQRPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGPGTRVDIR 1477 CD70- 3.001x1 2C bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGRGLEWVAVTWYDAS NRYYGDAVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDLLRGVRGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQRPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGPGTRVDIRSGGGGSE VQLVESGGGLVQPGGSLRLSCAASGFTF NRYAMNWVRQAPGRGLEWVARIRSRYNN YATYYADSVRDRFTISRDDSRNTAYLQM NNLRTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQRPGQAPRGLIGGTRFLA PGTPARFSGSLLGGRAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTRLTVL 1478 CD70- 4.007 VH CDR1 SYGIS 1479 CD70- 4.007 VH CDR2 WISAYQGYTHYAQRLQG 1480 CD70- 4.007 VH CDR3 DYGGNDYYGMDV

- 306 041992

1481 CD70- 4.007 VL CDR1 SGSSSNIGINYVY 1482 CD70- 4.007 VL CDR2 RSDQRPS 1483 CD70- 4.007 VL CDR3 AAFDESLSGW 1484 CD70- 4.007_C WITH vh QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQCLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSS 1485 CD70- 4.007_C WITH VL QSVLTQPPSASGTPGQRVTISCSGSSSN IGINYVYWYQQLPGTAPKLLIYRSDQRP SGVPDRFSGSKSGTSASLALSGLRSEDE ADYYCAAFDESLSGWFGCGTKLTVL 1486 CD70- 4.007_C WITH scFv QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQCLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGCGTKLTVL 1487 CD70- 4.007_C CxI2C bispecific molecule QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQCLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGCGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN

- 307 041992

NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWGYSNRWVLG 1488 CD70- 4.007 vh QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSS 1489 CD70- 4.007 VL QSVLTQPPSASGTPGQRVTISCSGSSSN IGINYVYWYQQLPGTAPKLLIYRSDQRP SGVPDRFSGSKSGTSASLALSGLRSEDE AD Y YCAAFDE S L S GWFGGGTKL T VL 1490 CD70- 4.007 scFv QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGGGTKLTVL 1491 CD70- 4.007x1 2C bispecific molecule QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGGGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT

- 308 041992

FNRYAMNWVRQAPGRGLEWVARIRSRYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 1492 CD70- 12.013 VH CDR1 YYGMH 1493 CD70- 12.013 VH CDR2 VIWYDASNKYYADAVKG 1494 CD70- 12.013 VH CDR3 DREMGSRGDFDY 1495 CD70- 12.013 VL CDR1 RASQGINNYLA 1496 CD70- 12.013 VL CDR2 AVSILQS 1497 CD70- 12.013 VL CDR3 QQYNFYPFS 1498 CD7012.013_CC vh QAQLVE S GGGWQPGRS LRL S CAAS G FT FSYYGMHWVRQAPGKCLEWVAVIWYDAS NKYYADAVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSS 1499 CD7012.013_CC VL DIQMTQSPSSLSASVGDRVTITCRASQG INNYLAWFQQRPGRAPRSLIYAVSILQS GVPSRFSGSGSGTDFTLTISNLQPEDFA TYYCQQYNFYPFSFGCGTRVDIR 1500 CD7012.013_CC scFv QAQLVE S GGGWQPGRS LRL S CAAS G FT FSYYGMHWVRQAPGRCLEWVAVIWYDAS NRYYADAVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY

- 309 041992

LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGCGTKVDIK 1501 CD7012.013_CCxI2C bispecific molecule QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKCLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1502 CD70- 12.013 vh QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKGLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSS 1503 CD70- 12.013 VL DIQMTQSPSSLSASVGDRVTITCRASQG INNYLAWFQQKPGKAPKSLIYAVSILQS GVPSKFSGSGSGTDFTLTISNLQPEDFA TYYCQQYNFYPFSFGQGTKVDIK 1504 CD70- 12.013 scFv QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKGLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM

- 310 041992

TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGQGTKVDIK 1505 CD70- 12.013x I2C bispecific molecule QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKGLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGQGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVL 1506 CD7075.002. 008 VH CDR1 GFYWS 1507 CD7075.002. 008 VH CDR2 EIYHSGHATNNPSLKS 1508 CD7075.002. 008 VH CDR3 GGNSGYIFDY 1509 CD70- 75.002. 008 VL CDR1 RTSQYIGRYLN 1510 CD70- VL CDR2 GASTLQQ

- 311 041992

75.002. 008 1511 CD7075.002. 008 VL CDR3 QQTYSTPRT 1512 CD7075.002. 008_CC vh QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKCLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSS 1513 CD7075.002. 008_CC VL DVQMTQSPSSLSASVGDRVTITCRTSQY IGRYLNWYQQKPGKAPKVLIYGAS TLQQ GVPSRFSGSGSGTDFTLTITSLQPEDFA SYYCQQTYSTPRTFGCGTKVEIK 1514 CD7075.002. 008_CC scFv QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKCLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGCGTKVEIK 1515 CD7075.002. 008_CCx I2C bispecificity molecular molecule QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKCLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGCGTKVEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY ADSVKDRFTISRDDSKNTAYLQMNNLKT

- 312 041992

EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGTKLTVL 1516 CD7075.002. 008 vh QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKGLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSS 1517 CD7075.002. 008 VL DVQMTQSPSSLSASVGDRVTITCRTSQY IGRYLNWYQQKPGKAPKVLIYGAS TLQQ GVPSRFSGSGSGTDFTLTITSLQPEDFA SYYCQQTYSTPRTFGQGTKVEIK 1518 CD7075.002. 008 scFv QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKGLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGQGTKVEIK 1519 CD70- 75.002. 008XI2C bispecificity molecular molecule QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKGLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGQGTKVEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY

- 313 041992

ADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGGG 1520 CD70- 1.005 VH CDR1 TYGMH 1521 CD70- 1.005 VH CDR2 VIWYEGSNKYYGESVKG 1522 CD70- 1.005 VH CDR3 DNSHYYYGMDV 1523 CD70- 1.005 VL CDR1 TGSSSNIGAGYDVN 1524 CD70- 1.005 VL CDR2 VNNNRPS 1525 CD70- 1.005 VL CDR3 QSYDTSLSASV 1526 CD70- 1.005_C WITH vh QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSS 1527 CD70- 1.005_C WITH VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAGYDVNWYQQFPGTAPKLLIYVNNNR PSGVPDRFSGSTSGTSASLAITGLQAED EADYYCQSYDTSLSASVFGCGTRLTVL 1528 CD70- 1.005_C WITH scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKL

- 314 041992

DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGCGTRLTVL 1529 CD70- 1.005_C CxI2C bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPRLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLRLSCAASGFT FNRYAMNWVRQAPGRGLEWVARIRSRYN NYATYYADSVRDRFTISRDDSRNTAYLQ MNNLRTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQRPGQAPRGLIGGTRFL APGTPARFSGSLLGGRAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTRLTVL 1530 CD70- 1.005 vh QVQLVE S GGGWQPGRS LRL S CAAS G FT 1531 CD70- 1.005 VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAGYDVNWYQQFPGTAPRLLIYVNNNR PSGVPDRFSGSTSGTSASLAITGLQAED EADYYCQSYDTSLSASVFGGGTRLTVL 1532 CD70- 1.005 scFv QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGRGLEWVAVIWYEGS NRYYGESVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY

- 315 041992

DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGGGTRLTVL 1533 CD70- 1.005x1 2C bispecificity molecular molecule QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 1534 CD70- 1.009 VH CDR1 TYGMH 1535 CD70- 1.009 VH CDR2 VIWYEGSNKYYGESVKG 1536 CD70- 1.009 VH CDR3 DNSHYYYGMDV 1537 CD70- 1.009 VL CDR1 TGSSSNIGAGYDVN 1538 CD70- 1.009 VL CDR2 VNNNRPS 1539 CD70- 1.009 VL CDR3 QSYETSLASV 1540 CD70- 1.009_C vh QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGKGLEWVAVIWYEGS

- 316 041992

WITH NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSS 1541 CD70- 1.009_С WITH VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAGYDVNWYQQLPGTAPKLLIYVNNNR PSGVPDRFSSGSKSGTSASLAITGLQAED EADYYCQSYETSLSASVFGCGTRLTVL 1542 CD70- 1.009_С WITH scFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGCGTRLTVL 1543 CD70- 1.00 9_С Сх12С bispecific molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL 1544 CD70- vh QVQLVE S GGGWQPGRS LRL S CAAS GET

- 317 041992

1.009 FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSS 1545 CD70- 1.009 VL QSVLTQPPSVSGAPGQRVTISCTGSSSN IGAGYDVNWYQQLPGTAPKLLIYVNNNR PSGVPDRFSSGSKSGTSASLAITGLQAED EADYYCQSYETSLSASVFGGGTRLTVL 1546 CD70- 1.009 SCFv QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGGGTRLTVL 1547 CD70- 1.009x1 2C bispecific molecule QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVL

- 318 041992

1548 CD70- 76.008 VH CDR1 SGVYYWS 1549 CD70- 76.008 VH CDR2 YIYYSGSTSYNPSLKS 1550 CD70- 76.008 VH CDR3 SGYSYALFDY 1551 CD70- 76.008 VL CDR1 RASQSVDRYFN 1552 CD70- 76.008 VL CDR2 AASSLQS 1553 CD70- 76.008 VL CDR3 QQSYSTPWT 1554 CD7076.008_CC vh QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKCLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSS 1555 CD7076.008_CC VL DIQMTQSPSSLSASLGDRVTITCRASQS VDRYFNWYQQKPGKAPKVLIFAAS S LQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSTPWTFGCGTKVEVK 1556 CD7076.008_CC scFv QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKCLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEVK 1557 CD7076.008_ CCxI2C bispecificity molecular molecule QMQLQESGPGLVKPSETLSLTTCTVSGGS IESGVYYWSWIRQPPGKCLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT

- 319 041992

QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEVKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1558 CD70- 76.008 vh QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKGLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSS 1559 CD70- 76.008 VL DIQMTQSPSSLSASLGDRVTITCRASQS VDRYFNWYQQKPGKAPKVLIFAAS S LQS GVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSYSTPWTFGQGTKVEVK 1560 CD70- 76.008 scFv QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKGLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEVK 1561 CD70- 76.008x I2C bispecificity molecular molecule QMQLQESGPGLVKPSETLSLTTCTVSGGS IESGVYYWSWIRQPPGKGLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ

- 320 041992

GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEVKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1562 CD70- 5.008 VH CDR1 SGGYYWS 1563 CD70- 5.008 VH CDR2 YIFYSGSTDYNPSLKS 1564 CD70- 5.008 VH CDR3 SGYSYALFDA 1565 CD70- 5.008 VL CDR1 RASQFIGRYFN 1566 CD70- 5.008 VL CDR2 AESSLQS 1567 CD70- 5.008 VL CDR3 QQSYSTPWT 1568 CD70- 5.008_C WITH vh QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSS 1569 CD70- 5.008_C WITH VL DIQMTQSPSSLSASVGDRVTISCRASQF IGRYFNWYQQKPGKAPKVLIYAESSLQS GVPSRFSGSGSGTEFTLTISSLQPEDFA TYYCQQSYSTPWTFGCGTKVEIK

- 321 041992

1570 CD70- 5.008_C WITH scFv QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEIK 1571 CD70- 5.008_C CxI2C bispecificity molecular molecule QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1572 CD70- 5.008 vh QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSS 1573 CD70- 5.008 VL DIQMTQSPSSLSASVGDRVTISCRASQF IGRYFNWYQQKPGKAPKVLIYAESSLQS GVPSRFSGSGSGTEFTLTISSLQPEDFA

- 322 041992

TYYCQQSYSTPWTFGQGTKVEIK 1574 CD70- 5.008 scFv QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKGLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEIK 1575 CD70- 5.008x1 2C bispecific molecule QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKGLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVL 1576 CD70- 13xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY

- 323 041992

LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1577 CD70- 13_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 324 041992

QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1578 CD70- 14xI2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 325 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1579 CD70- 14_CCxI 2C-scFc bispecific molecule EVQLLESGGGLVQPGGSLKLSCAASGFT ESIYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN

- 326 041992

HLE SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1580 CD70- 15xI2C- bispecificity chesky EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG

- 327 041992

scFc molecule HLE RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR CVSVLTVLHQDWLNGREYRCRVSNRALP APIERTISRARGQPREPQVYTLPPSREE MTRNQVSLTCLVRGFYPSDIAVEWESNG QPENNYRTTPPVLDSDGSFFLYSRLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGR 1581 CD70- bispecificity EVQLLESGGGMVQPGGSLRLSCAASGFT

- 328 041992

15_CCxI 2C-scFc chesky molecule HLE FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK

- 329 041992

1582 CD70- 16xI2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVM HEALHNHYTQKSL

- 330 041992

SLSPGK 1583 CD70- 16_CCxI 2C-scFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD

- 331 041992

KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1584 CD70- 17xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG

- 332 041992

QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1585 CD70- 17_CCxI 2C-scFc bispecific molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE

- 333 041992

MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1586 CD70- 18xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSKNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR CVSVLTVLHQDWLNGREYRCRVSNRALP

- 334 041992

APIERTISRARGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1587 CD70- 18_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNKALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR

- 335 041992

CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1588 CD70- 19xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV

- 336 041992

KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1589 CD70- 19_CCxI 2C-scFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP

- 337 041992

S 1590 CD70- 21xI2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG

- 338 041992

GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDFSDHFFLYSKLTVD KPSWQTLVKK 1591 CD70- 21_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG

- 339 041992

KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1592 CD70- 22xI2CscFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ

- 340 041992

QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1593 CD70- 22_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN

- 341 041992

YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1594 CD70- 24xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ

- 342 041992

VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1595 CD70- 24_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK

- 343 041992

TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1596 CD70- 25xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL

- 344 041992

TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1597 CD70- 25_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY

- 345 041992

VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1598 CD70- 26xI2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT

- 346 041992

LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1599 CD70- 26_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK

- 347 041992

THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1600 CD70_lG2xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 348 041992

YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1601 CD70_l- G2_CCxI 2C-scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG

- 349 041992

TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1602 CD70- 27xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGRCLEWVSAISGSGG GT FYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 350 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1603 CD70- 27_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 351 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1604 CD70- 28xI2CscFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW

- 352 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1605 CD70- 28_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN

- 353 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1606 CD70- 31xI2CscFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT

- 354 041992

YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1607 CD70- 31_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY

- 355 041992

AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1608 CD70- 32xI2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIKSGGGGSEVQ

- 356 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1609 CD70- 32_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQFTVRSDY LAWYQQKPGQAPRLLIYGASSRA

- 357 041992

QQYGSTPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1610 CD70- 37xI2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYPAQQKPGATGIAPRLLIYGASTR

- 358 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1611 CD70- 37_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKCLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY

- 359 041992

FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1612 CD70- 38xI2CscFc bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 360 041992

QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1613 CD70- 38_CCxI 2C-scFc bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 361 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1614 CD70- 39xI2CscFc bispecificity molecular molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN

- 362 041992

HLE SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1615 CD70- 39_CCxI bispecificity chesky EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG

- 363 041992

2C-scFc molecule HLE GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1616 CD70- bispecificity EVQLLESGGGMVQPGGSLRLSCAASGFT

- 364 041992

41xI2C- scFc chesky molecule HLE FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR CVSVLTVLHQDWLNGREYRCRVSNKALP APIERTISRARGQPREPQVYTLPPSREE MTRNQVSLTCLVRGFYPSDIAVEWESNG QPENNYRTTPPVLDSDGSFFLYSRLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGR

- 365 041992

1617 CD70- 41_CCxI 2C-scFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVM HEALHNHYTQKSL

- 366 041992

SLSPGK 1618 CD70- 42xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGRGLEWVSLISGSGG RTYYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR CVSVLTVLHQDWLNGREYRCRVSNRALP APIERTISRARGQPREPQVYTLPPSREE MTRNQVSLTCLVRGFYPSDIAVEWESNG QPENNYRTTPPVLDSDGSFFLYSRLTVD

- 367 041992

KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1619 CD70- 42_CCxI 2C-scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG

- 368 041992

QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1620 CD70- 43xI2CscFc bispecific molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE

- 369 041992

MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1621 CD70- 43_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP

- 370 041992

APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1622 CD70- 48xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC

- 371 041992

VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1623 CD70- 48_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK

- 372 041992

LSPGK 1624 CD70- 53xI2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP

- 373 041992

S 1625 CD70- 53_CCxI 2C-scFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG

- 374 041992

GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDFSDHFFLYSKLTVD KPSWQTLVKK 1626 CD70- 54xI2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG

- 375 041992

KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1627 CD70- 54_CCxI 2C-scFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ

- 376 041992

QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1628 CD70- 58xI2CscFc bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ

- 377 041992

PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKGGGGSGGGGSGGGGSGGGGSGGG GSGGGGSDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPCEEQYG STYRCVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK 1629 CD70- 58_CCxI 2C-scFc bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM

- 378 041992

TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKGGGGSGGGGSGGGGSGGGGSGGG GSGGGGSDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPCEEQYG STYRCVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK 1630 CD70- 62xI2CscFc bispecific HLE molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT

- 379 041992

ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1631 CD70- 62_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT

- 380 041992

VLHQDWLNGREYRCRVSNRALPAPIERT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQRSLSLSPGR GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQRSLS LSPGK 1632 CD70- 23xI2CscFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGRGLEWVSTISDSGG STFYADSVRGRFTISRDNSRNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY

- 381 041992

VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1633 CD70- 23_CCxI 2C-scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT

- 382 041992

LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1634 CD70- 55xI2CscFc bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG

- 383 041992

GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1635 CD70- 55_CCxI 2C-scFc bispecific molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKCLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED

- 384 041992

EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1636 CD70- 13xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 385 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1637 CD70- 13_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYADSVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 386 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1638 CD70- 14xI2CscFc_de 1GK bispecific molecule HLE EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW

- 387 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1639 CD70- 14_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT ESIYAMSWVRQAPGKCLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 388 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1640 CD70- 15xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 389 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1641 CD70- 15_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 390 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1642 CD70- 16xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ

- 391 041992

LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IERTISRARGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQRSLSL SPGK 1643 CD70- 16_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQQRPGQAPRLLIYGASSGRATGYFTD

- 392 041992

QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1644 CD70- 17xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRAD

- 393 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1645 CD70- 17_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY

- 394 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1646 CD70- 18xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 395 041992

QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1647 CD70- 18_CCxI 2C- scFc_de bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ

- 396 041992

1GK GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1648 CD70- 19xI2CscFc_de bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLSLQMN

- 397 041992

1GK HLE SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1649 CD70- 19_CCxI bispecificity chesky EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG

- 398 041992

2C- scFc_de 1GK molecule HLE STFYADSVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1650 CD70- bispecificity EVQLLESGGGMVQPGGSLRLSCAASGFT

- 399 041992

21xI2CscFc_de 1GK chesky molecule HLE FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK

- 400 041992

1651 CD70- 21_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDRTHTCPPCPAPELLGGPSVFLFPPRP RDTLMISRTPEVTCVWDVSHEDPEVRF NWYVDGVEVHNARTRPCEEQYGSTYRCV SVLTVLHQDWLNGREYRCRVSNRALPAP IERTISRARGQPREPQVYTLPPSREEMT RNQVSLTCLVRGFYPSDIAVEWESNGQP ENNYRTTPPVLDSDGSFFLYSRLTVDRS RWQQGNVFSCSVMHE ALHNHYTQRSSLSL

- 401 041992

SPGK 1652 CD70- 22xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS

- 402 041992

RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1653 CD70- 22_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP

- 403 041992

ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1654 CD7024xI2CscFc_de 1GK bispecific molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT

- 404 041992

KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1655 CD70- 24_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP

- 405 041992

IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1656 CD70- 25xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV

- 406 041992

SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1657 CD70- 25_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF

- 407 041992

NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1658 CD70- 26xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP

- 408 041992

KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1659 CD70- 26_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG

- 409 041992

SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTVMTPVLDSDGSHYFFLYSKLTVDKS RWQKHE 1660 CD70_lG2xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG

- 410 041992

GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1661 CD70_lG2_CCxI 2CscFc_de 1GK bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYADSVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ

- 411 041992

QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQRSLSL SPGK 1662 CD70- 27xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN

- 412 041992

YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1663 CD70- 27_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ

- 413 041992

VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1664 CD70- 28xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK

- 414 041992

TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1665 CD70- 28_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL

- 415 041992

TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1666 CD70- 31xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV

- 416 041992

DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1667 CD70- 31_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYADSVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL

- 417 041992

MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1668 CD70- 32xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK

- 418 041992

THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1669 CD70- 32_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 419 041992

YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1670 CD70- 37xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKGLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG

- 420 041992

TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1671 CD70- 37_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FS SYAMSWVRQAPGKCLEWVSAIGDGGG YTYYADSVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 421 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQRSLSL SPGK 1672 CD70- 38xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 422 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1673 CD70- 38_CCxI 2C- scFc_de 1GK bispecific molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW

- 423 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1674 CD70- 39xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 424 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1675 CD70- 39_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 425 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1676 CD70- 41xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR

- 426 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1677 CD70- 41_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIKSGGGGSEVQ

- 427 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1678 CD70- 42xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRAINLT

- 428 041992

QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1679 CD70- 42_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRAPD

- 429 041992

RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQRSLSL SPGK 1680 CD70- 43xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSRNNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY

- 430 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1681 CD70- 43_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 431 041992

QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1682 CD70- 48xI2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ

- 432 041992

GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1683 CD70- 48_CCxI 2C- bispecificity chesky molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISDSGG ITDFADSVKGRFTISRDNSRNTLYLQMN

- 433 041992

scFc_de 1GK HLE SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1684 CD70- 53xI2C- bispecificity chesky EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG

- 434 041992

scFc_de 1GK molecule HLE RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1685 CD70- bispecificity EVQLLESGGGMVQPGGSLRLSCAASGFT

- 435 041992

53_CCxI 2C- scFc_de 1GK chesky molecule HLE FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYADSVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK

- 436 041992

1686 CD70- 54xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEA LHNHYTQKSLSL

- 437 041992

SPGK 1687 CD70- 54_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGDSGG STFYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS

- 438 041992

RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1688 CD70- 58xI2CscFc_de 1GK bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES

- 439 041992

NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1689 CD70- 58_CCxI 2C- scFc_de 1GK bispecific HLE molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR

- 440 041992

EEMTKNQVSLTCLVKGFYPSDIAVEVES NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1690 CD70- 62xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI

- 441 041992

EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1691 CD70- 62_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYADSVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS

- 442 041992

VLTVLHQDWLNGREYRCRVSNRALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQRSLSLS PGK 1692 CD70- 23xI2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGRGLEWVSTISDSGG STFYADSVRGRFTISRDNSRNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDRTHTCPPCPAPELLGGPSVFLFPPRP RDTLMISRTPEVTCVWDVSHEDPEVRF

- 443 041992

NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1693 CD70- 23_CCxI 2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISDSGG STFYADSVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP

- 444 041992

KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1694 CD70- 55xI2CscFc_de 1GK bispecific HLE molecule QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG

- 445 041992

GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1695 CD70- 55_CCxI 2C- scFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKCLEWVAVISYDGS NKYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL

- 446 041992

SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DRSRWQQGNVFSCSVMHEALHNHYTQRS LSLSPGK 1696 CD70- 13D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSVISGSGG RPNYAESVKGRFTISRDNSRNTLYLQMN SLRDEDTAVYYCARVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN

- 447 041992

YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1697 CD70- 13DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ

- 448 041992

VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1698 CD70- 14D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLKLSCAASGFT ESIYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK

- 449 041992

TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1699 CD70- 14DxI2C -scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL

- 450 041992

TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1700 CD70_61 DlD_CCx I2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY

- 451 041992

VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1701 CD70_61 DlDxI2C -scFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT

- 452 041992

LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1702 CD70- 16D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK

- 453 041992

THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1703 CD70- 16DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE

- 454 041992

YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1704 CD70- 17D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG

- 455 041992

TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1705 CD70- 17DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 456 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1706 CD70- 18D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 457 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1707 CD70- 18DxI2C -scFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSKYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW

- 458 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1708 CD70- 19D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 459 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1709 CD70- 19DxI2C -scFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 460 041992

ТYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1710 CD70- 21D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR

- 461 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1711 CD70- 21DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ

- 462 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1712 CD70- 22D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRALT

- 463 041992

QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1713 CD70- 22DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRGLEWVSAISGSGG YTYYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD

- 464 041992

RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1714 CD70- 24D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY

- 465 041992

LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1715 CD70- 24DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 466 041992

QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1716 CD70- 25D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 467 041992

GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1717 CD70- 25DxI2C -scFc bispecific molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN

- 468 041992

HLE SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1718 CD70- 26D_CCx bispecificity chesky EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG

- 469 041992

I2C- scFc molecule HLE RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1719 CD70- bispecificity EVQLLESGGGMVQPGGSLRLSCAASGFT

- 470 041992

26DxI2C -scFc chesky molecule HLE FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK

- 471 041992

1720 CD70_lG2D_CCx I2C- scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMH EALHNHYTQKSL

- 472 041992

SLSPGK 1721 CD70_lG2DxI2C -scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD

- 473 041992

KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1722 CD70- 27D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG

- 474 041992

QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1723 CD70- 27DxI2C -scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR CVSVLTVLHQDWLNGREYRCRVSNRALP APIERTISRARGQPREPQVYTLPPSREE

- 475 041992

MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1724 CD70- 28D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP

- 476 041992

APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1725 CD70- 28DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR

- 477 041992

CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1726 CD70- 31D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKCLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK

- 478 041992

LSPGK 1727 CD70- 31DxI2C -scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK

- 479 041992

PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA 1728 CD70- 32D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG

- 480 041992

GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDFSDHFFLYSKLTVD KPSWQTLVKK 1729 CD70- 32DxI2C -scFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG

- 481 041992

KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1730 CD70- 37D_CCx I2CscFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ

- 482 041992

QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1731 CD70- 37DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN

- 483 041992

YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1732 CD70- 38D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ

- 484 041992

VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1733 CD70- 38DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER

- 485 041992

TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1734 CD70- 39D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG GT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL

- 486 041992

TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1735 CD70- 39DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY

- 487 041992

VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1736 CD70- 41D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT

- 488 041992

LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1737 CD70- 41DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR

- 489 041992

THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1738 CD70- 42D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 490 041992

YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1739 CD70- 42DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG

- 491 041992

TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGK 1740 CD70- 43D_CCx I2CscFc bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 492 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1741 CD70- 43DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 493 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG RGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDRTHTCPPCPAPELLGGPSVFLFPP RPRDTLMISRTPEVTCVWDVSHEDPEV RFNWYVDGVEVHNARTRPCEEQYGSTYR CVSVLTVLHQDWLNGREYRCRVSNRALP APIERTISRARGQPREPQVYTLPPSREE MTRNQVSLTCLVRGFYPSDIAVEWESNG QPENNYRTTPPVLDSDGSFFLYSRLTVD RSRWQQGNVFSCSVMHEALHNHYTQRSL SLSPGR 1742 CD70- 48D_CCx I2CscFc bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGRCLEWVSVISGSGG ITDFAESVRGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQRPGRVPRLLIYAASILQSGVPSR FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIRSGGGGSEVQL VESGGGLVQPGGSLRLSCAASGFTFNRY AMNWVRQAPGRGLEWVARIRS RYNNYAT YYADSVRDRFTISRDDSRNTAYLQMNNL RTEDTAVYYCVRHGNFGNSYISYWAYWG

- 494 041992

QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1743 CD70- 48DxI2C -scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFATYYCQ QYFAYPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL

- 495 041992

KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1744 CD70- 53D_CCx I2CscEc bispecific molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 496 041992

ТYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1745 CD70- 53DxI2C -scFc bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 497 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1746 CD70- 54D_CCx I2CscFc bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIKSGGGGSEVQ

- 498 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA ТYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1747 CD70- 54DxI2C -scFc bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLDLIYGASSCCLTY

- 499 041992

QQYGDLPFTFGPGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1748 CD7058D_CCx I2CscFc bispecific HLE molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKL

- 500 041992

GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKGGGGSGGGGSGGGGSGGGGSGGG GSGGGGSDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPCEEQYG STYRCVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK 1749 CD70- 58DxI2C -scFc bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS

- 501 041992

ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKGGGGSGGGGSGGGGSGGGGSGGG GSGGGGSDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPCEEQYG STYRCVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK 1750 CD70- 62D_CCx I2CscFc bispecific HLE molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT

- 502 041992

QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1751 CD70- 62DxI2C -scFc bispecificity chesky molecule HLE EVQLVESGGGLVKPGGSLRLSCAASGFT FS S YSMNWVRQAPGKCLEWVS YIS S S GG YIYYAESVKGRFTISRDNAKNSLYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ

- 503 041992

GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1752 CD70- 23D_CCx I2C- bispecific molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN

- 504 041992

scFc HLE RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1753 CD70- 23DxI2C bispecificity chesky EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISGSGG

- 505 041992

-scFc molecule HLE STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1754 CD70- bispecificity QVQLVE S GGGWQPGRS LRL S CAAS G FM

- 506 041992

55D_CCx I2CscFc chesky molecule HLE FSSYGMHWVRQAPGKCLEWVAVISYEGS NKYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK

- 507 041992

1755 CD70- 55DxI2C -scFc bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYEGS NKYYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQRPGRAPRLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTRVEIRSGGGGS EVQLVESGGGLVQPGGSLRLSCAASGFT FNRYAMNWVRQAPGRGLEWVARIRSRYN NYATYYADSVRDRFTISRDDSRNTAYLQ MNNLRTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQRPGQAPRGLIGGTRFL APGTPARFSGSLLGGRAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTRLTVLGGG GDRTHTCPPCPAPELLGGPSVFLFPPRP RDTLMISRTPEVTCVWDVSHEDPEVRF NWYVDGVEVHNARTRPCEEQYGSTYRCV SVLTVLHQDWLNGREYRCRVSNRALPAP IERTISRARGQPREPQVYTLPPSREEMT RNQVSLTCLVRGFYPSDIAVEWESNGQP ENNYRTTPPVLDSDGSFFLYSRLTVDRS RWQQGNVFSCSVMHEALHNHYTQRSLSL SPGRGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDRTHTCPPCPAPELLGGPSVFL FPPRPRDTLMISRTPEVTCVWDVSHED PEVRFNWYVDGVEVHNARTRPCEEQYGS TYRCVSVLTVLHQDWLNGREYRCRVSNR ALPAPIERTISRARGQPREPQVYTLPPS REEMTRNQVSLTCLVRGFYPSDIAVEWE SNGQPENNYRTTPPVLDSDGSFFLYSRL TVDRSRWQQGN VFSCSVMHEALHNHYTQ

- 508 041992

KSLSLSPGK 1756 CD703.001_C CxI2CscFc bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDLLRGVRGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQRPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGCGTRVDIRSGGGGSE VQLVESGGGLVQPGGSLRLSCAASGFTF NRYAMNWVRQAPGRGLEWVARIRSRYNN YATYYADSVRDRFTISRDDSRNTAYLQM NNLRTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQRPGQAPRGLIGGTRFLA PGTPARFSGSLLGGRAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTRLTVLGGGG DRTHTCPPCPAPELLGGPSVFLFPPRPR DTLMISRTPEVTCWVDVSHEDPEVRFN WYVDGVEVHNARTRPCEEQYGSTYRCVS VLTVLHQDWLNGREYRCRVSNRALPAPI ERTISRARGQPREPQVYTLPPSREEMTR NQVSLTCLVRGFYPSDIAVEWESNGQPE NNYRTTPPVLDSDGSFFLYSRLTVDRSR WQQGNVFSCSVMHEALHNHYTQRSLSLS PGRGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDRTHTCPPCPAPELLGGPSVFLF PPRPRDTLMISRTPEVTCVWDVSHEDP EVRFNWYVDGVEVHNARTRPCEEQYGST YRCVSVLTVLHQDWLNGREYRCRVSNRA LPAPIERTISRARGQPREPQVYTLPPSR EEMTRNQVSLTCLVRGFYPSDIAVEWES NGQPENNYRTTPPVLDSDGSFFLYSRLT

- 509 041992

VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1757 CD70- 3.001x1 2C-scFc bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKGLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGPGTKVDIKSGGGGSE VQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNN YATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTKLTVLGGGG DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES

- 510 041992

NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1758 CD704.007_C CxI2CscFc bispecific HLE molecule QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQCLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGCGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS

- 511 041992

REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1759 CD70- 4.007x1 2C-scFc bispecificity chesky molecule HLE QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGGGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK

- 512 041992

ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1760 CD7012.013_CCxI2CscFc bispecificity chesky molecule HLE QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKCLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR

- 513 041992

CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1761 CD7012.013x I2CscFc bispecificity chesky molecule HLE QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKGLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGQGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG KGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV

- 514 041992

KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1762 CD7075.002. 008_CCx I2C- scFc bispecificity chesky molecule HLE QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKCLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGCGTKVEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY ADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPCEEQYGSTYRCVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK

- 515 041992

DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1763 CD7075.002. 008XI2C -scFc bispecific HLE molecule QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKGLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGQGTKVEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY ADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPCEEQYGSTYRCVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS

- 516 041992

DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSLDSDGSHFFLYSKLTVDKSRWQQQ 1764 CD701.005_C CxI2CscFc bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL

- 517 041992

SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1765 CD70- 1.005x1 2C-scFc bispecific molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS

- 518 041992

RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1766 CD70- 1.00 9_C CxI2C- scFc bispecific HLE molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP

- 519 041992

ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1767 CD70- 1.009x1 2C-scFc bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT

- 520 041992

KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKGGGGSGGGGSGGGGSGGGGSGGGG SGGGGSDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPCEEQYGS TYRCVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPS REEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK 1768 CD7076.008_ CCxI2CscFc bispecificity chesky molecule HLE QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKCLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEVKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT

- 521 041992

ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1769 CD7076.008x I2CscFc bispecific HLE molecule QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKGLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEVKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT

- 522 041992

VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1770 CD705.008_C CxI2CscFc bispecific HLE molecule QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV

- 523 041992

DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1771 CD70- 5.008x1 2C-scFc bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKGLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL

- 524 041992

MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGK 1772 CD70- 13D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSVISGSGG RPNYAESVKGRFTISRDNSKNTLYLQMN SLRDEDTAVYYCAKVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 525 041992

YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP RDTLMISRTPEVTCVWDVSHEDPEVRF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1773 CD70- 13DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG RPNYAESVKGRFTISRDNSRNTLYLQMN SLRDEDTAVYYCARVDYSNYLFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGEGATLSCRAGQSVRSSY LGWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPPTFGGGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG

- 526 041992

TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1774 CD70- 14D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 527 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1775 CD70- 14DxI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLKLSCAASGFT FSIYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 528 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1776 CD70_61 DlD_CCx I2CscFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW

- 529 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1777 CD70_61 DlDxI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTFYAESVEGRFTISRDNSKNTLFLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 530 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1778 CD70- 16D_CCx I2C- scFc_de 1GK bispecific molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA

- 531 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1779 CD70- 16DxI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 532 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1780 CD70- 17D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKLEIKSGGGGSEVQ

- 533 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1781 CD70- 17DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQSGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRALT

- 534 041992

QQYGSSPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1782 CD70- 18D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSLISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYDASSRAPD

- 535 041992

RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1783 CD70- 18DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSLISGSGG RTHYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY

- 536 041992

LAWYQQKPGQAPRLLIYDASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1784 CD70- 19D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT

- 537 041992

QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1785 CD70- 19DxI2C scFc_de bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLSLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 538 041992

1GK GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1786 CD70- 21D_CCx I2C- bispecificity molecular molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN

- 539 041992

scFc_de 1GK HLE SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1787 CD70- 21DxI2C bispecificity chesky EVQLLESGGGMVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG

- 540 041992

scFc_de 1GK molecule HLE RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSTY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1788 CD70- bispecificity EVQLLESGGGLVQPGGSLRLSCAASGFT

- 541 041992

22D_CCx I2C- scFc_de 1GK chesky molecule HLE FSSYAMSWVRQAPGKCLEWVSAISGSGG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK

- 542 041992

1789 CD70- 22DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG YTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEA LHNHYTQKSLSL

- 543 041992

SPGK 1790 CD70- 24D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS

- 544 041992

RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1791 CD70- 24DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLAQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP

- 545 041992

ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1792 CD70- 25D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT

- 546 041992

KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1793 CD70- 25DxI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP

- 547 041992

IERTISRARGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQRSSLSL SPGK 1794 CD70- 26D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDRTHTCPPCPAPELLGGPSVFLFPPRP RDTLMISRTPEVTCVWDVSHEDPEVRF NWYVDGVEVHNARTRPCEEQYGSTYRCV

- 548 041992

SVLTVLHQDWLNGREYRCRVSNRALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1795 CD70- 26DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDRTHTCPPCPAPELLGGPSVFLFPPRP RDTLMISRTPEVTCVWDVSHEDPEVRF

- 549 041992

NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1796 CD70_lG2D_CCx I2CscFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER TISKARGQPREPQVYTLPPSREEMTRNQ VSLTCLVRGFYPSDIAVEWESNGQPENN YRTTPPVLDSDGSFFLYSRLTVDRSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDRTHTCPPCPAPELLGGPSVFLFPPRP

- 550 041992

KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1797 CD70_lG2DxI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG STFYAESVQGRFTISRDNSKNTLYLQVN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRGNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGYSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG

- 551 041992

SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTVMTPVLDSDGSHYFFLYSKLTVDKS RWQKHE 1798 CD70- 27D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG

- 552 041992

GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1799 CD70- 27DxI2C scFc_de 1GK bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ

- 553 041992

QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1800 CD70- 28D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKCLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN

- 554 041992

YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1801 CD70- 28DxI2C scFc_de 1GK bispecific molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASNRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGISPPTFGGGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ

- 555 041992

VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1802 CD70- 31D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT

- 556 041992

ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1803 CD70- 31DxI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQSPGKGLEWVSAISGSGG RAQYAESVQGRFTVSRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPATLSVSPGERATLSCRASQSVSSNL AWYQQKPGQAPRLLIYGSSSRATGIPDR FSGSGSGTDFTLTISRLEPEDFAVYYCQ QYGSSPPPFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT

- 557 041992

VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1804 CD70- 32D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY

- 558 041992

VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1805 CD70- 32DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSDY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYHC QQYGSTPPTFGGGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSKYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT

- 559 041992

LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1806 CD70- 37D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK

- 560 041992

THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1807 CD70- 37DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAIGEGGG YTYYAESVKGRFTISRDNSKNTLSLLMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY FAWYQQKPGQAPRLLIYGASTRATGIPA RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPTFGQGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE

- 561 041992

YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1808 CD70- 38D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKCLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG

- 562 041992

TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1809 CD70- 38DXI2C scFc_de 1GK bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSIRSNY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSSPPSFGQGTRVEIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS

- 563 041992

GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1810 CD70- 39D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV

- 564 041992

VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1811 CD70- 39DxI2C scFc_de 1GK bispecific molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG GT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGL GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYSC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW

- 565 041992

GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1812 CD70- 41D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN

- 566 041992

LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP RDTLMISRTPEVTCVWDVSHEDPEVRF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1813 CD70- 41DxI2C scFc_de 1GK bispecific molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCTRHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA

- 567 041992

TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1814 CD70- 42D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK

- 568 041992

YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISRARGQPREPQVYTLPPSREEMTRNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1815 CD70- 42DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSTYAMSWVRQAPGKGLEWVSLISGSGG RTYYAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQGVRSSY LAWYQQRPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTRVDIRSGGGGSEVQ

- 569 041992

LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1816 CD70- 43D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRALTG

- 570 041992

QQYGSSPPTFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1817 CD70- 43DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGWQPGRSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSNY LAWYQQKPGQAPRLLIYGASSRAD

- 571 041992

RFSGSGSGTDFTLTINRLEPEDFAVYYC QQYGSSPPTFGGGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1818 CD70- 48D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG ITDFAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL

- 572 041992

AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGCGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1819 CD70- 48DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSVISGSGG ITDFAESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYFCARHDYSNYFFFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT

- 573 041992

QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASILQSGVPSK FSGSGSGTDFTLTISSLQPEDFAIYYCQ QYFAYPITFGQGTRLEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1820 CD70- 53D_CCx I2CscFc_de bispecificity chesky molecule HLE EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ

- 574 041992

1GK GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1821 CD70- 53DxI2C bispecific molecule EVQLLESGGGMVQPGGSLRLSCAASGFT FSSYAMSWVRQAPGKGLEWVSAISGSGG RT FYAESVEGRFTISRDNSRNTLYLQMN

- 575 041992

scFc_de 1GK HLE SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYFC QQYGSSPPTFGGGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1822 CD70- 54D_CCx bispecificity chesky EVQLLESGGGLVQPGGSLRLSCAASGFT FSIYAMSWVRQAPGKCLEWVSAIGGSGG

- 576 041992

I2CscFc_de 1GK molecule HLE STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1823 CD70- bispecificity EVQLLESGGGLVQPGGSLRLSCAASGFT

- 577 041992

54DxI2C scFc_de 1GK chesky molecule HLE ESIYAMSWVRQAPGKGLEWVSAIGGSGG STFYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKHDYSNYPYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY VAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTRLEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK

- 578 041992

1824 CD70- 58D_CCx I2C- scFc_de 1GK bispecific HLE molecule QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKCLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGCGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVM HEALHNHYTQK

- 579 041992

SLSLSPGK 1825 CD70- 58DxI2C scFc_de 1GK bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGGS ISSSSYYWGWIRQPPGKGLEWIGSIYHS GGTYFNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARHYEILTGYYPDVF DIWGQGTMVTVSSGGGGSGGGGSGGGGS DIQMTQSPSSLSASVGDRVTITCRASQS ISSYLNWYQQKPGKAPKLLIYAASNLQS GVSSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQSFSSPRTFGQGTKVEIKSGGGG SEVQLVESGGGLVQPGGSLKLSCAASGF TFNKYAMNWVRQAPGKGLEWVARIRSKY NNYATYYADSVKDRFTISRDDSKNTAYL QMNNLKTEDTAVYYCVRHGNFGNSYISY WAYWGQGTLVTVSSGGGGSGGGGSGGGG SQTWTQEPSLTVSPGGTVTLTCGSSTG AVTSGNYPNWVQQKPGQAPRGLIGGTKF LAPGTPARFSGSLLGGKAALTLSGVQPE DEAEYYCVLWYSNRWVFGGGTKLTVLGG GGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPCEEQYGSTYRC VSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLT

- 580 041992

VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1826 CD70- 62D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FS SYSMNWVRQAPGKCLEWVSYIS S S GG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE

- 581 041992

NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1827 CD70- 62DxI2C scFc_de 1GK bispecific HLE molecule EVQLVESGGGLVKPGGSLRLSCAASGFT FSSYSMNWVRQAPGKGLEWVSYISSSGG YIYYAE SVKGRFTIS RDNAKNS LYLQMN SLRAEDAAVYYCSRGDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTITCRASQGISNYL AWYQQKPGKVPKLLIYAASTLQSGVPSR FSGSGSGTDFTLTISSLQAEDVAVYYCQ QYYSTPLTFGGGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK

- 582 041992

NQVSLTCLVKGFYPSDIAVESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1828 CD70- 23D_CCx I2C- scFc_de 1GK bispecific HLE molecule EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKCLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGCGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP

- 583 041992

IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1829 CD70- 23DxI2C scFc_de 1GK bispecificity chesky molecule HLE EVQLLESGGGLVQPGGSLRLSCAASGFT FSVYAMSWVRQAPGKGLEWVSTISGSGG STFYAESVKGRFTISRDNSKNTLYLQMN RLRAEDTAVYYCARHDYSNYAYFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSEIVLT QSPGTLSLSPGERATLSCRASQSVRSSY LAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGDLPFTFGPGTKVEIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV

- 584 041992

SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1830 CD70- 55D_CCx I2C- scFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKCLEWVAVISYEGS NKYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGCGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE

- 585 041992

LSLSPGK 1831 CD70- 55DxI2C scFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FM FSSYGMHWVRQAPGKGLEWVAVISYEGS NKYYAESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGRYYGSGNYNHGMD VWGQGTTVTVSSGGGGSGGGGSGGGGSD IQMTQSPSSLSASVGDRVTITCRASQSI SSYLNWYQQKPGKAPKLLIYAASSLQSG VPSRFSGRGSGTDFTLTISSLQPEDFAT YYCQQSYSTPFTFGPGTKVEIKSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP

- 586 041992

PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRFSVMKSHEALHNHYT 1832 CD70- 3.001_C CxI2C- scFc_de 1GK bispecific HLE molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSSYGMHWVRQAPGKCLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGCGTKVDIKSGGGGSE VQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNN YATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTKLTVLGGGG DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGGGGSGGGGSGGGGSGGGGSGGGGSGG

- 587 041992

GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDFSDHFFLYSKLTVD KPSWQTLVKK 1833 CD70- 3.001x1 2C- scFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FT FSSYGMHWVRQAPGKGLEWVAVTWYDAS NKYYGDAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDLLRGVKGYAMDVW GQGTTVTVSSGGGGSGGGGSGGGGSEIV LTQSPGTLSLSPGERATLSCRASQSLRR IYLAWYQQKPGQAPRLLIYDVFDRATGI PDRFSGGGSGTDFTLTISRLEPEDFAVY YCQQYSESPFTFGPGTKVDIKSGGGGSE VQLVESGGGLVQPGGSLKLSCAASGFTF NKYAMNWVRQAPGKGLEWVARIRSKYNN YATYYADSVKDRFTISRDDSKNTAYLQM NNLKTEDTAVYYCVRHGNFGNSYISYWA YWGQGTLVTVSSGGGGSGGGGSGGGGSQ TWTQEPSLTVSPGGTVTLTCGSSTGAV TSGNYPNWVQQKPGQAPRGLIGGTKFLA PGTPARFSGSLLGGKAALTLSGVQPEDE AEYYCVLWYSNRWVFGGGTKLTVLGGGG DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS

- 588 041992

PGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK 1834 CD704.007_C CxI2CscFc_de 1GK bispecific molecule HLE QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQCLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGCGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS

- 589 041992

RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1835 CD704.007x1 2CscFc_de 1GK bispecificity chesky molecule HLE QVQLVQSGAEVKKPGASVKVSCKASGYT FTSYGISWVRQAPGQGLEWMGWISAYQG YTHYAQKLQGRVTMTTDTSTSTAYMELR S LRS DDTAVYYCARDYGGNDYYGMDVWG QGTTVTVSSGGGGSGGGGSGGGGSQSVL TQPPSASGTPGQRVTISCSGSSSNIGIN YVYWYQQLPGTAPKLLIYRSDQRPSGVP DRFSGSKSGTSASLALSGLRSEDEADYY CAAFDESLSGWFGGGTKLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP

- 590 041992

ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1836 CD7012.013_ CCxI2CscFc_de 1GK bispecific HLE molecule QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKCLEWVAVIWYDAS NKYYADAVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQKPGKAPKSLIYAVSILQSGVPS KFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGCGTKVDIKSGGGGSEVQ LVESGGGLVQPGGSLKLSCAASGFTFNK YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNN LKTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQKPGQAPRGLIGGTKFLAPG TPARFSGSLLGGKAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTKLTVLGGGGDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ

- 591 041992

VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQRSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGREYRCRVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQRSLSL SPGK 1837 CD7012.013x I2CscFc_de 1GK bispecificity chesky molecule HLE QAQLVE S GGGWQPGRS LRL S CAAS GET FSYYGMHWVRQAPGKGLEWVAVIWYDAS NKYYADAVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDREMGSRGDFDYWG QGTLVTVSSGGGGSGGGGSGGGGSDIQM TQSPSSLSASVGDRVTITCRASQGINNY LAWFQQRPGRAPRSLIYAVSILQSGVPS RFSGSGSGTDFTLTISNLQPEDFATYYC QQYNFYPFSFGQGTRVDIRSGGGGSEVQ LVESGGGLVQPGGSLRLSCAASGFTFNR YAMNWVRQAPGRGLEWVARIRSRYNNYA TYYADSVRDRFTISRDDSRNTAYLQMNN LRTEDTAVYYCVRHGNFGNSYISYWAYW GQGTLVTVSSGGGGSGGGGSGGGGSQTV VTQEPSLTVSPGGTVTLTCGSSTGAVTS GNYPNWVQQRPGQAPRGLIGGTRFLAPG TPARFSGSLLGGRAALTLSGVQPEDEAE YYCVLWYSNRWVFGGGTRLTVLGGGGDR THTCPPCPAPELLGGPSVFLFPPRPRDT LMISRTPEVTCVWDVSHEDPEVRFNWY VDGVEVHNARTRPCEEQYGSTYRCVSVL TVLHQDWLNGREYRCRVSNRALPAPIER

- 592 041992

TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG GGGSGGGGSGGGGSGGGGSGGGGSGGGG SDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGK 1838 CD7075.002. 008_CCx I2CscFc_de 1GK bispecificity chesky molecule HLE QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKGLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGCGTKVEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY ADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPCEEQYGSTYRCVSVLTVL

- 593 041992

HQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGGGG SGGGGSGGGGSGGGGSGGGGSGGGGSDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG К 1839 CD7075.002. 008XI2C scFc_de 1GK bispecificity chesky molecule HLE QVQLQQWGAGLLKPSETLSLTCAVYGGS FSGFYWSWIRQPPGKGLEWIGEIYHSGH ATNNPSLKSRVTISLDTSKNQFSLKLNS VTAADTAVYYCARGGNSGYIFDYWGQGT LVTVSSGGGGSGGGGSGGGGSDVQMTQS PSSLSASVGDRVTITCRTSQYIGRYLNW YQQKPGKAPKVLIYGASTLQQGVPSRFS GSGSGTDFTLTITSLQPEDFASYYCQQT YSTPRTFGQGTKVEIKSGGGGSEVQLVE SGGGLVQPGGSLKLSCAASGFTFNKYAM NWVRQAPGKGLEWVARIRSKYNNYATYY ADSVKDRFTISRDDSKNTAYLQMNNLKT EDTAVYYCVRHGNFGNSYISYWAYWGQG TLVTVSSGGGGSGGGGSGGGGSQTWTQ EPSLTVSPGGTVTLTCGSSTGAVTSGNY PNWVQQKPGQAPRGLIGGTKFLAPGT PA RFSGSLLGGKAALTLSGVQPEDEAEYYC VLWYSNRWVFGGGTKLTVLGGGGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG

- 594 041992

VEVHNAKTKPCEEQYGSTYRCVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQRSLSLSPGGGG SGGGGSGGGGSGGGGSGGGGSGGGGSDK THTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPCEEQYGSTYRCVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG К 1840 CD70- 1.005_C CxI2CscFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKCLEWVAVIWYEGS NKYYGESVKGRFTISRDNSRNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPRLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLRLSCAASGFT FNRYAMNWVRQAPGRGLEWVARIRSRYN NYATYYADSVRDRFTISRDDSRNTAYLQ MNNLRTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQRPGQAPRGLIGGTRFL APGTPARFSGSLLGGRAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTRLTVLGGG GDRTHTCPPCPAPELLGGPSVFLFPPRP

- 595 041992

KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1841 CD70- 1.005x1 2CscFc_de 1GK bispecific HLE molecule QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTTVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQFPGTAPKLLIYVNNNRPSGVP DRFSGSTSGTSASLAITGLQAEDEADYY CQSYDTSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG

- 596 041992

GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1842 CD70- 1.00 9_C CxI2C- scFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS G FT FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGCGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL APGTPARFSGSLLGGKAALTLSGVQPED

- 597 041992

EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1843 CD70- 1.009x1 2CscFc_de 1GK bispecificity chesky molecule HLE QVQLVE S GGGWQPGRS LRL S CAAS GET FSTYGMHWVRQAPGKGLEWVAVIWYEGS NKYYGESVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDNSHYYYGMDVWGQ GTLVTVSSGGGGSGGGGSGGGGSQSVLT QPPSVSGAPGQRVTISCTGSSSNIGAGY DVNWYQQLPGTAPKLLIYVNNNRPSGVP DRFSGSKSGTSASLAITGLQAEDEADYY CQSYETSLSASVFGGGTRLTVLSGGGGS EVQLVESGGGLVQPGGSLKLSCAASGFT FNKYAMNWVRQAPGKGLEWVARIRSKYN NYATYYADSVKDRFTISRDDSKNTAYLQ MNNLKTEDTAVYYCVRHGNFGNSYISYW AYWGQGTLVTVSSGGGGSGGGGSGGGGS QTWTQEPSLTVSPGGTVTLTCGSSTGA VTSGNYPNWVQQKPGQAPRGLIGGTKFL

- 598 041992

APGTPARFSGSLLGGKAALTLSGVQPED EAEYYCVLWYSNRWVFGGGTKLTVLGGG GDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKF NWYVDGVEVHNAKTKPCEEQYGSTYRCV SVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSL SPGGGGSGGGGSGGGGSGGGGSGGGGSG GGGSDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVWDVSHEDPE VKFNWYVDGVEVHNAKTKPCEEQYGSTY RCVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRE EMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK 1844 CD7076.008_ CCxI2CscFc_de 1GK bispecificity chesky molecule HLE QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKCLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEVKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG

- 599 041992

NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1845 CD7076.008x I2CscFc_de 1GK bispecific HLE molecule QMQLQESGPGLVKPSETLSLTCTVSGGS IESGVYYWSWIRQPPGKCLEWIGYIYYS GSTSYNPSLKSRLTMSVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDYWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASLGDRVTITCRASQSVDRYF NWYQQKPGKAPKVLIFAASSLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEVKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW

- 600 041992

TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1846 CD705.008_C CxI2CscFc_de 1GK bispecific molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGCGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRS KYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL KTEDTAVYYCVRHGNFGNSYISYWAYWG

- 601 041992

QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1847 CD705.008x1 2CscFc_de 1GK bispecificity chesky molecule HLE QVQLQESGPGLVKPSQTLSLTCTVSGDS IISGGYYWSWIRQPPGKCLEWIGYIFYS GSTDYNPSLKSRVTISVDTSKNQFSLKL SSVTAADTAVYYCARSGYSYALFDAWGQ GTLVTVSSGGGGSGGGGSGGGGSDIQMT QSPSSLSASVGDRVTISCRASQFIGRYF NWYQQKPGKAPKVLIYAESSLQSGVPSR FSGSGSGTEFTLTISSLQPEDFATYYCQ QSYSTPWTFGQGTKVEIKSGGGGSEVQL VESGGGLVQPGGSLKLSCAASGFTFNKY AMNWVRQAPGKGLEWVARIRSKYNNYAT YYADSVKDRFTISRDDSKNTAYLQMNNL

- 602 041992

KTEDTAVYYCVRHGNFGNSYISYWAYWG QGTLVTVSSGGGGSGGGGSGGGGSQTW TQEPSLTVSPGGTVTLTCGSSTGAVTSG NYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEY YCVLWYSNRWVFGGGTKLTVLGGGGDKT HTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPCEEQYGSTYRCVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGG GGSGGGGSGGGGSGGGGSGGGGSGGGGS DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGK 1848 Monomer Fc 1 +c/-g DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSLDSDGSHFFLYSKLTVDKSRWQQQ 1849 Monomer DKTHTCPPCPAPELLGGPSVFLFPPKPK

- 603 041992

Fc 2 +c/-g/delGK P 1850 Monomer Fc 3 -c/ + g DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPVLDSDGSHFFLYSKLTVLSNKSR WQQQQVLSNKSR 1851 Monomer Fc 4 c/ + g/ delGK DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSALSDGSHFFLYSKLTVDKSR PQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSALSDGSHFFLYSKLTVDKSR 1852 Monomer Fc 5 -c/-g DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYGSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSALSDGSHFFLYSKLTVLSNKS WQQ

- 604 041992

1853 Monomer Fc 6 -s/-d/delGK DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYGSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSALSDGSHFFLYSKLTVDKSR PQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSALSDGSHFFLYSKLTVDKSR WQTHTCPPVLDSDGSHFFLYSKLTVDKSR PQVSLTCLVKGFYPSDIAVEWESNGQPE 1854 Monomer Fc 7 + s/ + d DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYNSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSALSDGSHFFLYSKLTVDKSRWQQQ 1855 Monomer Fc 8 +s/+d/ delGK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYNSTYRCVS 1856 scFc-1 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTVMTPKSLDGSHFFLYSKLTVDKSR

- 605 041992

PGKGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYGST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1857 scFc-2 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYGSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYGSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSP 1858 scFc-3 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR

- 606 041992

WQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNST YRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1859 scFc-4 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSP 1860 scFc-5 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYGSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE

- 607 041992

NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYGST YRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1861 scFc-6 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYGSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYGSTYR WSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSP 1862 scFc-7 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYNSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK

- 608 041992

NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGGGGSGGGGSGGGGSGGGGSGGGGS GGGGSDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVWDVSHEDP EVKFNWYVDGVEVHNAKTKPCEEQYNST YRCVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 1863 scFc-8 DKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPCEEQYNSTYRCVS VLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLS PGGGGSGGGGSGGGGSGGGGSGGGGSGG GGSDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEV KFNWYVDGVEVHNAKTKPCEEQYNSTYR CVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSREE MTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSL SLSP 1864 Linker (G ₄ S) ₄ GGGGSGGGGSGGGGSGGGGS 1865 Linker GGGGSGGGGSGGGGSGGGGSGGGGS

- 609 041992

( _G4S )5 1866 Linker (G ₄ S) ₆ GGGGSGGGGSGGGGSGGGGSGGGGSGGG GS 1867 Linker (G ₄ S) ₇ GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSGGGGS 1868 Linker (G ₄ S) ₈ GGGGSGGGGSGGGGSGGGGSGGGGSGGG GSGGGGSGGGGS 1869 consensus sequence VH-CDR1 ΧιΥΧ ₂ ΜΧ ₃ Xi is S, T or V, X ₂ is A or S and X ₃ is S or N 1870 consensus sequence VH-CDR2 XiISX ₂ SG GX ₃ X ₄ X ₅ X ₆ aesvx ₇ g Xi is A, Y, V, L or T, X ₂ is G or S, X3 is R, Y, S, G or I, X ₄ is T, I, P or A, X ₅ is F, Y, N, Q or D, X ₆ is Y or F and X ₇ is E, K or Q 1871 consensus sequence VH-CDR3 XiDYSNY X2X3FDY Xi is H, G or V, X ₂ is P, A, L or F, and X ₃

- 610 041992

represents Y or F 1872 consensus sequence VL-CDR1 RAXiQX ₂ X ₃ X ₄ X ₅ X ₆ X7 lx ₈ X ₂ is S or G, X ₂ is S or G, Xs is I or V, X ₄ is R, S or no amino acid, X ₅ is S or G, X ₆ is S, N, T or D, X ₇ is Y or no amino acid, and X ₈ is A or G 1873 consensus sequence VL-CDR2 X1X _{2SX 3} X ₄ X ₅ X ₆ X ₂ is G or A, X ₂ is A or S, X ₃ is S, T, N or I, X ₄ is R or L, X ₅ is A or Q and X ₆ is T or S 1874 Consensus oral VL-CDR3 QQYXiX ₂ X ₃ PX ₄ X ₅ X ₂ is G, Y or F,

- 611 041992

subsequence X ₂ is D, S, Y, I or A, X ₃ is L, T, S or Y, X ₄ is F, L, P or I and X ₅ is T or P 1875 consensus sequence VH-CDR1 X1YAMS Xi represents a S, T or V 1876 consensus sequence VH-CDR2 X1ISGSG GX ₂ X ₃ X ₄ Y AESVX ₅ G Xi is A, V, L or T, X ₂ is R, S or G, X ₃ is T, P or A, X ₄ is F, N, Y or Q, and X ₅ is E, K or Q 1877 consensus sequence VH-CDR3 XiDYSNY X2X3FDY Xi is H or V, X ₂ is P, L or A and X ₃ is Y or E 1878 Consensus VL-CDR1 RAXiQX ₂ X ₃ X ₄ X ₅ X ₆ Y lx ₇ Xi is S or G, X ₂ is S or G, X ₃

- 612 041992

awn is I or V, X ₄ is R or S, X ₅ is S or G, X ₆ is S, T, N or D, and X ₇ is A or G 1879 consensus sequence VL-CDR2 AASXLQS X represents a T or I 1880 consensus sequence VL-CDR2 GXiSX _2RA T Xi is A or S and X ₂ is S or N 1881 consensus sequence VL-CDR3 QQYGXiX ₂ PX3X4 Xi is D, Y, S or I, X ₂ is L, S or T, X ₃ is F or P and X ₄ is T or P

CLAIM

Claims (18)

1. A bispecific antibody construct comprising a first binding domain that binds to human CD70 on the surface of a target cell and a second binding domain that binds to human CD3 on the surface of a T cell, wherein the first binding domain contains a VH region containing CDR-H1 , CDR-H2 and CDR-H3, and a VL region containing CDR-L1, CDR-L2 and CDR-L3, where said CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR- L3 are selected from the group consisting of the groups: 16) SEQ ID NO: 1044-1049; 17) SEQ ID NO: 1086-1091; 18) SEQ ID NO: 1142-1147; 19) SEQ ID NO: 1170-1175; 20) SEQ ID NO: 1184-1189; 21) SEQ ID NO: 1212-1217; 22) SEQ ID NO: 1226-1231; 23) SEQ ID NO: 1240-1245; 24) SEQ ID NO: 1254-1259; 25) SEQ ID NO: 1268-1273; 26) SEQ ID NO: 1338-1343; 27) SEQ ID NO: 1352-1357; 28) SEQ ID NO: 1366-1371; 29) SEQ ID NO: 1422-1427; And 30) SEQ ID NO: 1436-1441; 2. An antibody construct according to claim 1, wherein the first binding domain comprises a VH region selected from the group consisting of those shown in SEQ ID NO: 1050, SEQ ID NO: 1092, SEQ ID NO: 1148, SEQ ID NO: 1176, SEQ ID NO: 1190, SEQ ID NO: 1218, SEQ ID NO: 1232, SEQ ID NO: 1246, SEQ ID NO: 1260, SEQ ID NO: 1274, SEQ ID NO: 1344, SEQ ID NO: 1358, SEQ ID NO: 1372, SEQ ID NO: 1428 and - 613 041992 SEQ ID NO: 1442. 3. An antibody construct according to claim 1 or 2, wherein the first binding domain comprises a VL region selected from the group consisting of SEQ ID NO: 1051, SEQ ID NO: 1093, SEQ ID NO: 1149, SEQ ID NO: 1177, SEQ ID NO: 1191, SEQ ID NO: 1219, SEQ ID NO: 1233, SEQ ID NO: 1247, SEQ ID NO: 1261, SEQ ID NO: 1275, SEQ ID NO: 1345, SEQ ID NO: 1359, SEQ ID NO : 1373, SEQ ID NO: 1429 and SEQ ID NO: 1443. 4. An antibody construct according to any one of the preceding claims, wherein the first binding domain comprises a VH region and a VL region selected from the group consisting of pairs of a VH region and a VL region: SEQ ID NO: 1050+1051, SEQ ID NO: 1092+1093, SEQ ID NO: 1148+1149, SEQ ID NO: 1176+1177, SEQ ID NO: 1190+1191, SEQ ID NO: 1218+1219, SEQ ID NO: 1232+1233, SEQ ID NO: 1246+1247, SEQ ID NO: 1260+1261, SEQ ID NO: 1274+1275, SEQ ID NO: 1344+1345, SEQ ID NO: 1358+1359, SEQ ID NO: 1372+1373, SEQ ID NO: 1428+1429 and SEQ ID NO: 1442+1443. 5. An antibody construct according to any one of the preceding claims, wherein the first binding domain comprises a polypeptide selected from the group consisting of SEQ ID NO: 1052, SEQ ID NO: 1094, SEQ ID NO: 1150, SEQ ID NO: 1178, SEQ ID NO : 1192, SEQ ID NO: 1220, SEQ ID NO: 1234, SEQ ID NO: 1248, SEQ ID NO: 1262, SEQ ID NO: 1276, SEQ ID NO: 1346, SEQ ID NO: 1360, SEQ ID NO: 1374 , SEQ ID NO: 1430 and SEQ ID NO: 1444. 6. An antibody construct according to any one of the preceding claims, comprising a polypeptide selected from the group consisting of SEQ ID NO: 1053, SEQ ID NO: 1095, SEQ ID NO: 1151, SEQ ID NO: 1179, SEQ ID NO: 1193, SEQ ID NO: 1221, SEQ ID NO: 1235, SEQ ID NO: 1249, SEQ ID NO: 1263, SEQ ID NO: 1277, SEQ ID NO: 1347, SEQ ID NO: 1361, SEQ ID NO: 1375, SEQ ID NO : 1431 and SEQ ID NO: 1445. 7. An antibody construct according to any one of the preceding claims, comprising or consisting of a polypeptide selected from the group consisting of SEQ ID NO: 1696, SEQ ID NO: 1702, SEQ ID NO: 1710, SEQ ID NO: 1714, SEQ ID NO: 1716, SEQ ID NO: 1720, SEQ ID NO: 1722, SEQ ID NO: 1724, SEQ ID NO: 1726, SEQ ID NO: 1728, SEQ ID NO: 1738, SEQ ID NO: 1740, SEQ ID NO: 1742, SEQ ID NO: 1750 and SEQ ID NO: 1752. 8. An antibody construct according to any one of the preceding claims, wherein the first binding domain also binds to macaque CD70, preferably Macaca fascicularis CD70. 9. An antibody construct according to any one of the preceding claims, wherein the second binding domain binds to human CD3 epsilon and to Callithrix jacchus, Saguinus Oedipus or Saimiri sciureus CD3 epsilon. 10. An antibody construct according to any one of the preceding claims, wherein the antibody construct is in a format selected from the group consisting of (scFv) ₂ , single domain scFv mAb, diabodies, and oligomers of the above formats. 11. A polynucleotide encoding an antibody construct according to any of the preceding claims. 12. A vector containing a polynucleotide according to claim 11. 13. A host cell for expressing an antibody construct according to any one of claims 1 to 10, transformed or transfected with a polynucleotide according to claim 11 or a vector according to claim 12. 14. A method for producing an antibody construct according to any one of claims 1 to 10, wherein the method comprises culturing the host cell according to claim 13 under conditions allowing said antibody construct to be expressed, and isolating the produced antibody construct from the culture. 15. Pharmaceutical composition for the prevention or treatment of a tumor or oncological disease, containing the antibody construct according to any one of claims 1 to 10 or obtained by the method according to claim 14. 16. The use of an antibody construct according to any one of claims 1 to 10 or obtained by the method of claim 14 for the prevention or treatment of a tumor or cancer or metastatic cancer. 17. Use according to claim 16, where the tumor or oncological disease is selected from the group consisting of cancer of the kidney, lung, pancreas, ovary, breast, colon, head and neck, stomach, rectum, thymus, brain; leukemia, lymphoma, melanoma, Kaposi's sarcoma, embryonic carcinoma, and metastatic cancer. 18. A kit for the treatment of a tumor or oncological disease, containing the antibody construct according to any one of claims 1 to 10, the antibody construct obtained by the method according to claim 14, the polynucleotide according to claim 11, the vector according to claim 12 and / or the host cell according to item 13.