DOMÍNIOS DE LIGAÇÃO AO ANTÍGENO ANTI-5T4, CONJUGADOS DE ANTICORPO-FÁRMACO E MÉTODOS DE USO DOS MESMOS

Abstract

The disclosure provides anti-5T4 antigen binding domains, which can be incorporated into antibodies and receptors, including bispecific anti-5T4 antibodies, biparatopic anti-5T4 antibodies, and antibody-drug conjugates of same comprising a first antigen binding domain that specifically binds to a first 5T4 epitope, a second antibody antigen binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope, wherein the first antigen binding domain is operably linked to the second antigen binding domain, and a chemotherapeutic agent. The disclosure further provides methods of using same for the treatment of cancer.

Description

[001] This application claims priority and the benefit of U.S. Provisional Application No. 63 / 453,929, filed March 22, 2023, the contents of which are incorporated herein by reference in their entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[002] The contents of the electronic sequence listing (SBTI005_001WO_SeqList_St26.xml; Size: 163,004 bytes; and Creation Date: February 29, 2024) are incorporated herein by reference in their entirety. BACKGROUND

[003] Cancer is a leading cause of death in the developed world. In the United States alone, an estimated 1.8 million people were recently diagnosed, and over 600,000 cancer deaths occurred in 2020. In cancer, an individual's cells grow and divide abnormally, spreading to surrounding tissues. It is believed that each cancer has a combination of genetic alterations, which can vary between cancers, allowing cancer cells to escape the body's natural controls over cell proliferation and allowing the cancer to spread. While some types of cancer are currently treatable, many are not. There is a need in technology for compositions and methods for cancer treatment.

[004] Human 5T4 manifests in a variety of cancer types, including bladder cancer, breast cancer, cervical cancer, endometrial cancer, lung cancer, esophageal cancer, ovarian cancer, pancreatic cancer, gastric cancer, and testicular cancer. Human 5T4 is generally not found in normal tissues and, when Petition 870250084408, dated 09 / 19 / 2025, page 13 / 297 2 / 214, found, is expressed at low levels, making it an ideal therapeutic target for cancer treatment. The present invention provides antibodies and antibody-drug conjugates comprising chemotherapeutic agents that bind specifically to a first and, in some cases, a second 5T4 epitope, compositions comprising the same, and methods of production and use thereof in the treatment of diseases such as cancer. SUMMARY

[005] The invention provides 5T4 antigen-binding domains, as well as antibodies, antibody-drug conjugates and receptors comprising the same.

[006] The invention provides biparatropic 5T4 drug-antibody conjugates comprising: (a) a first antigen-binding domain that specifically binds to a first 5T4 epitope; (b) an antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and (c) a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain. In some embodiments of the biparatropic 5T4 antibodies and antibody-drug conjugates described herein, the biparatropic antibody or antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprises an scFv.

[007] In some embodiments of the antibody-drug conjugates of the invention, the N-terminal of the second antigen-binding domain is operably linked to the C-terminal of a heavy chain of the first antigen-binding domain. In some embodiments, the C-terminal of the second antigen-binding domain is operably linked to the N-terminal of a heavy chain of the first Petition 870250084408, dated 09 / 19 / 2025, p. 14 / 297 3 / 214 antigen-binding domain. In some embodiments, the second antigen-binding domain is operably linked to the heavy chain of the first antigen-binding domain using a linker. In some embodiments, the antibody or antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprises an scFv, and the antibody or antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising, from the N-terminal to the C-terminal, the heavy chain of the first antigen-binding domain, a linker, and the second antigen-binding domain; and (b) two polypeptides comprising the light chain of the first antigen-binding domain.In some embodiments, the antibody or antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain and the second antigen-binding domain comprising an scFv, and the antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising, from the N-terminal to the C-terminal, the second antigen-binding domain, a ligand, and the heavy chain of the first antigen-binding domain; and (b) two polypeptides comprising the light chain of the first antigen-binding domain.

[008] In some embodiments, the chemotherapeutic agent is an auristatin, for example, an auristatin selected from the group consisting of auristatin E (AE), monomethyl auristatin D (MMAD), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF) and synthetic dolastatin analogues.

[009] The invention provides nucleic acid systems and vectors that encode the antigen, antibody and receptor binding domains of the invention. Petition 870250084408, dated 09 / 19 / 2025, page 15 / 297 4 / 214

[0010] The invention provides pharmaceutical compositions comprising antigen-binding domains, antibodies, antibody-drug conjugates and immune cells comprising receptors of the invention.

[0011] The invention provides pharmaceutical compositions comprising antigen-binding domains, antibodies, antibody-drug conjugates and immune cells comprising receptors of the invention, for use in the treatment of cancer in an individual.

[0012] The invention provides pharmaceutical compositions comprising antigen-binding domains, antibodies, antibody-drug conjugates and immune cells comprising receptors of the invention, for use in the manufacture of a medicament for the treatment of cancer in an individual.

[0013] The invention provides methods for treating cancer in an individual in need thereof, the method comprising administering to an individual in need thereof a therapeutically effective amount of an antigen-binding domain, antibody, antibody-drug conjugate or immune cells comprising the receptor of the invention. In some embodiments, the methods comprise administering an antibody-drug conjugate comprising (a) a first antigen-binding domain that specifically binds to a first 5T4 epitope; (b) a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and (c) a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain.

[0014] The invention provides methods for the manufacture of antibody-drug conjugates, the method comprising: (a) culturing a cell comprising a nucleic acid system encoding the anti Petition 870250084408, dated 09 / 19 / 2025, page 16 / 297 5 / 214 body under conditions that lead to antibody expression, (b) recover the antibody; and (c) conjugate the antibody to a chemotherapeutic agent. BRIEF DESCRIPTION OF THE FIGURES

[0015] FIGS. 1A to 1B are schematic diagrams describing the structural configuration of exemplary biparatopic anti5T4 antibody-drug conjugates. FIG. 1A shows a first exemplary drug-antibody conjugate (Bs2 orientation). FIG. 1B shows a second exemplary drug-antibody conjugate (Bs3 orientation). VH: variable heavy chain; VL: variable light chain; scFv: variable single-chain fragment.

[0016] FIGS. 2A to 2C show graphs and a table describing the size exclusion chromatography analysis after purification of protein A from four exemplary biparatopic anti-5T4 antibodies. FIG. 2A depicts two graphs showing the monomer peak analysis of two exemplary antibodies in the Bs2 orientation shown in FIG. 1A. The graph on the left shows an antibody with scFv in the VL-VH orientation, while the graph on the right shows an antibody with scFv in the VH-VL orientation. FIG. 2B illustrates two graphs showing the monomer peak analysis of two exemplary antibodies in the Bs3 orientation, shown in FIG. 1B. The graph on the left shows an antibody with scFv in the VL-VH orientation, while the graph on the right shows an antibody with scFv in the VH-VL orientation.Table 2C shows the quantitative yield of soluble protein, in mg / L, and the relative purity, by size exclusion chromatography (SEC) peak, for the antibody variations shown in FIGS. 2A to 2B from a 10-day culture harvest.

[0017] Figures 3A to 3C are two graphs and a table describing an SPR-based binding assay to confirm that the 5T4 epitopes bound by antibodies 1 and 2 are non-competitive. Petition 870250084408, dated 09 / 19 / 2025, p. 17 / 297 6 / 214 FIG. 3A shows an assay in which mouse Ab1 ((m)Ab1) was captured on the sensor chip using anti-mouse IgG antibodies, followed by injection of 5T4 and then humanized Ab1 or Ab2 with human Fc. FIG. 3B shows an assay in which mouse Ab2 ((m)Ab2) was captured on the sensor chip using anti-mouse IgG antibodies, followed by injection of 5T4 and then humanized Ab1 or Ab2 with human Fc. FIG. 3C is a table showing the legend that displays the binding sensorgram and injection samples for FIGS. 3A to 3B. The y-axis in FIGS. 3A and 3B indicates the relative response (in resonance units, or RU), while the x-axis indicates the time (in seconds, or s).

[0018] FIGS. 4A to 4E show the binding affinity of parental monospecific antibodies and biparatopic antibodies to 5T4, as determined by Biacore analysis. FIG. 4A shows the binding of a first exemplary monospecific antibody, the humanized antibody Ab1. FIG. 4B shows the binding of a second exemplary monospecific antibody, the humanized antibody Ab2. FIG. 4C shows the binding of an exemplary biparatopic antibody in the Bs3 orientation with scFv in the VH-VL orientation (Bs3-HL). FIG. 4D shows the binding of a second exemplary biparatopic antibody (Bs3-HL-FCA, Bs3 with scFv in the VH-VL orientation and with the L234F, S239C and N434A mutations). Table 4E summarizes the equilibrium dissociation constants (KD), dissociation rate constants (Kd), and association rate constants (Ka) of the antibody binding assays in FIGS. 4A to 4D. For FIGS. 4A to 4D, the y-axis shows the response (in RU) and the x-axis shows the time (in seconds).

[0019] FIG. 5 is a table showing the percentage of sequence identity of rhesus monkey, cynomolgus monkey, mouse and rat 5T4 proteins with the human 5T4 protein.

[0020] FIG. 6 is a graph representing the binding of an anti Petition 870250084408, dated 09 / 19 / 2025, page 18 / 297 7 / 214 Biparatopic 5T4 body specimen in Bs3 orientation to 5T4 protein from various species using an ELISA assay. NHP: non-human primate.

[0021] FIGS. 7A to 7D are a series of graphs representing the binding specificity of an exemplary biparatopic antibody in the Bs3 orientation to the 5T4 protein of various species, as determined by surface plasmon resonance (SPR). FIG. 7A shows binding to human 5T4 protein. FIG. 7B shows binding to NHP 5T4 protein. NHP: non-human primate. FIG. 7C shows binding to mouse 5T4 protein. FIG. 7D shows binding to rat 5T4 protein. The y-axis in all FIGS. 7A to 7D indicates the relative response (in RU), while the x-axis indicates time (in seconds). In FIGS. In groups 7A to 7D, the antibody concentrations are as follows: 100 nM (purple), 33.3 nM (yellow), 11.1 nM (pink), 3.7 nM (green), 1.2 nM (orange), and 133 pM (blue).

[0022] FIG. 8 is a table describing the summary of equilibrium dissociation constants (KD) for the binding of an exemplary biparatopic antibody in the Bs3 HL format with the Fc mutation shown in FIG. 1A and a parental Ab1 without the Fc mutations to select Fc gamma receptors (FcyRs). FCA: L234F, S239C, and N434A mutations.

[0023] FIGS. 9A to 9L show a series of graphs describing the flow cytometry analysis of 5T4 expression on the cell surface in a panel of 5T4-negative and 5T4-positive cell lines. FIG. 9A shows AGS cells. FIG. 9B shows HepG2 cells. FIG. 9C shows LoVo cells. FIG. 9D shows PCI-N87 cells. FIG. 9E shows A549 cells. Figure 9F shows DU145 cells. Figure 9G shows PANC-1 cells. Figure 9H shows T-47D cells. Figure 9I shows MCF7 cells. Figure 9J shows HEK293-5T4 (3G9) cells. Figure 9K shows HEK293-5T4 (4F2) cells. Figure 9L shows HEK293-5T4 (5C10) cells.

[0024] Figures 10A to 10F are a series of graphs that represent Petition 870250084408, dated 09 / 19 / 2025, page 19 / 297 Figure 8 / 214 shows the internalization of the 5T4 receptor induced by biparatopic antibodies in the Bs3-HL and Bs2-HL formats, with or without the FCA mutations (L234F, S239C, and N434A), compared to parental monospecific antibodies (humanized versions of the Ab1 and Ab2 antibodies). 5T4 receptor internalization was evaluated in multiple cell types expressing 5T4. FIG. 10A shows DU145 cells. FIG. 10B shows PANC-1 cells. FIG. 10C shows MCF7 cells. FIG. 10D shows HEK293-5T4 (3G9) cells. FIG. 10E shows HEK293-5T4 (4F2) cells. FIG. 10F shows T-47D cells.

[0025] FIGS. 11A to 11F are a series of graphs representing the mean percent viability of cancer cell lines incubated with biparatopic antibodies in the Bs3-HL format conjugated with MMAE, compared with a non-specific IgG antibody for 5T4 (IgG-Ctrl) conjugated with MMAE and MMAE controls (no antibody). Viability was assessed in multiple cell types expressing 5T4. FIG. 11A shows AGS cells. FIG. 11B shows DU145 cells. FIG. 11C shows T-47D cells. FIG. 11D shows MCF7 cells. FIG. 11E shows HEK293-5T4 (3G9) cells. FIG. 11F shows HEK293-5T4 (4F2) cells. cc4 and cc8 indicate different drug-antibody ratios (DARs), of approximately 4 and 8, respectively. The y-axis shows the percent viability, while the x-axis indicates the concentration of the drug-antibody conjugate (in pM). MMAE: monomethyl auristatin E.

[0026] FIGS. 12A to 12F are a series of graphs representing the mean percentage inhibition of growth of cancer cell lines incubated with biparatopic 5T4 antibodies in Bs3-HL format conjugated with MMAE, compared with a non-specific 5T4 IgG antibody (IgG-Ctrl) conjugated with MMAE and MMAE controls (no antibody). Growth inhibition was evaluated in multiple cell types expressing 5T4. FIG. 12A shows Petition 870250084408, dated 09 / 19 / 2025, page 20 / 297 Figure 12A shows DU145 cells. Figure 12C shows MCF7 cells. Figure 12D shows T-47D cells. Figure 12E shows HEK293-5T4 (3G9) cells. Figure 12F shows HEK293-5T4 (4F2) cells. cc4 and cc8 indicate different drug-antibody ratios (DARs), of approximately 4 and 8, respectively. The y-axis shows the percentage of growth inhibition, while the x-axis indicates the concentration of the drug-antibody conjugate (in pM). MMAE; monomethyl auristatin E.

[0027] FIGS. 13A and 13B are two graphs representing tumor growth and survival in immunocompromised mice implanted with NCI-H1975 lung adenocarcinoma tumors and treated with biparatopic 5T4 antibody in the Bs3 orientation, conjugated with MMAE (two dose concentrations), compared with the isotypic control antibody conjugated with MMAE and the sham control with PBS. FIG. 13A shows tumor growth. FIG. 13B shows the probability of survival. ADC: drug-antibody conjugate; MMAE: monomethyl auristatin E.

[0028] FIGS. 14A to 14C are a series of graphs representing tumor growth in immunocompromised mice implanted with various CDX tumor models and treated with biparatopic 5T4 antibody in the Bs3 orientation, conjugated to MMAE (multiple concentrations), compared with MMAE-conjugated isotype control antibody or PBS sham control. FIG. 14A shows an MDA-MD-361 breast cancer model. FIG. 14B shows a DU145 prostate carcinoma model. FIG. 14C shows an A549 lung carcinoma model. ADC: drug-antibody conjugate; MMAE; monomethyl auristatin E.

[0029] FIGS. 15A-15D are a series of sensorgrams representing the binding affinity of parental 5T4 antibodies compared to biparatopic 5T4 antibodies in the configuration Petition 870250084408, dated 09 / 19 / 2025, page 21 / 297 10 / 214 FIG. 15A shows the binding affinity of the parental antibody (m)Ab1. FIG. 15B shows the binding affinity of the parental antibody (m)Ab2. FIG. 15C shows the binding affinity of the bispecific antibody in the Bs3-HL orientation. FIG. 15D shows the binding affinity of the bispecific antibody in the Bs3-HL orientation conjugated to MMAE; monomethyl auristatin E.

[0030] FIG. 16 is a table that describes the summary of equilibrium dissociation constants (KD) for the binding of 5T4 antibodies, as shown in FIGS. 15A-15D, with and without conjugation with MMAE, to 5T4. DETAILED DESCRIPTION

[0031] The description provides antigen-binding domains that specifically bind to 5T4 and methods for producing and using them. The 5T4 antigen-binding domains of the present invention include, but are not limited to, Fab fragments, F(ab')2 fragments, scFv, scab, dAb, single-domain antibodies, full-size IgG antibodies, and the like. Non-limiting uses of the 5T4 antigen-binding domains contemplated within the scope of the present invention include immunotherapies, use as antibody-drug conjugates, and incorporation into chimeric antigen receptors (CARs) used in adoptive cell therapies.

[0032] Consequently, the invention provides antibody-drug conjugates comprising the 5T4 antigen-binding domains described herein. In some embodiments, the drug-antibody conjugate is biparatopic, that is, it comprises a first antigen-binding domain that binds specifically to a first 5T4 epitope and a second antigen-binding domain that binds to a second 5T4 epitope, and the two 5T4 epitopes are not the same. In some embodiments, the antibody-drug conjugate comprises a first antigen-binding domain that binds specifically to Petition 870250084408, dated 09 / 19 / 2025, page 22 / 297 11 / 214 a first 5T4 epitope and a second antigen-binding domain that binds specifically to a second 5T4 epitope that is not the same as the first 5T4 epitope and comprises a chemotherapeutic agent.

[0033] The biparatopic antibodies and antibody-drug conjugates of the present invention bind to two different epitopes of the same target molecule 5T4, thus cross-linking 5T4 on the surface of cells, such as cancer cells, and inducing the formation of 5T4-antibody immune complexes. This enhanced cross-linking provides a functional benefit over known 5T4-binding proteins, such as monospecific antibodies or other proteins that bind specifically to a single 5T4 epitope. Such benefits include more robust and rapid internalization of the 5T4 molecules bound to the drug-antibody complex, which may lead to improved cytotoxic elimination of target cancer cells.Without intending to limit oneself to theory, it is believed that increased cross-linking and / or aggregation of antibody immune complexes leads to more robust internalization, lysosomal trafficking, and degradation of immune complexes within cells, and intracellular release of cytotoxic payloads within host cells. The biparatopic antibody-drug conjugates described herein exhibit enhanced internalization and specific elimination of 5T4-expressing cancer cells. Thus, the biparatopic antibodies and antibody-drug conjugates of the present invention may provide greater potency against cancer cells and a more effective treatment for individuals with 5T4-positive cancers.

[0034] In some embodiments, the biparatopic antibodies and antibody-drug conjugates of the present invention comprise an IgG constant region (Fc) domain comprising at least one mutation that reduces effector function and prolongs half-life. Petition 870250084408, dated 09 / 19 / 2025, p. 23 / 297 12 / 214 or a combination thereof. For example, Fc mutations in the antibody-drug conjugates presented here provide an additional benefit over known 5T4-binding proteins in the prior art, reducing affinity at least to the Fc gamma I receptor (FcyRI) and / or the Fc gamma IIIa receptor (FcyRII) compared to antibodies without Fc mutations, without decreasing the binding affinity of the antibody-drug conjugates to 5T4. Exemplary Fc mutations that minimize antibody effector function and prolong the half-life of antibody-drug conjugates are shown in Table 3.

[0035] In some embodiments, the biparatopic antibodies of the invention comprise a first antigen-binding domain operably linked to a second antigen-binding domain. In some embodiments, the first and second antigen-binding domains are independently selected from the group consisting of a Fab fragment, an F(ab')2 fragment, an scFv, a scab, a dAb, a single-domain heavy chain antibody, a single-domain light chain antibody, and a full-size IgG antibody. In some embodiments, the biparatopic antibody comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprises an scFv. In some embodiments, the chemotherapeutic agent is conjugated to at least one of the full-size IgG antibodies comprising the first antigen-binding domain or the second antigen-binding domain by means of a linker.In some embodiments, the chemotherapeutic agent is an auristatin, such as, for example, but not limited to, auristatin E (AE), monomethyl auristatin D (MMAD), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and synthetic dolastatin analogues.

[0036] Also provided here are polynucleotides and vectors encoding antigen-, antibody- and conjugate-binding domains. Petition 870250084408, dated 09 / 19 / 2025, page 24 / 297 13 / 214 antibody-drug conjugates comprising the same, and chimeric antigen receptors (CARs) comprising the antigen-binding domains of the invention, as well as pharmaceutical compositions comprising the same, and methods for their production and use thereof. Antigen-binding domains, antibodies, antibody-drug conjugates and CARs can be used to treat a variety of diseases and disorders, including cancers. Definitions

[0037] Unless defined otherwise, the technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains.

[0038] For the purposes of interpreting this descriptive report, the following definitions shall apply and, where appropriate, terms used in the singular shall also include the plural and vice versa. If any definition set forth below conflicts with any document incorporated herein by reference, the definition set forth below shall prevail.

[0039] The term individual, as used herein, includes, but is not limited to, a mammal, including, for example, a human being, a non-human primate (e.g., monkey), mouse, pig, cow, goat, rabbit, rat, guinea pig, hamster, horse, monkey, sheep or other non-human mammal, a non-mammal, including, for example, a non-mammalian vertebrate, such as a bird (e.g., a chicken or duck) or a fish; and a non-mammalian invertebrate. In some embodiments, the methods and compositions of the invention are used to treat (both prophylactically and therapeutically) non-human animals. The term individual may also refer to patients, i.e., individuals awaiting or receiving medical care.

[0040] The term pharmaceutical composition here means a Petition 870250084408, dated 09 / 19 / 2025, page 25 / 297 14 / 214 composition suitable for pharmaceutical use in an individual, including an animal or human. A pharmaceutical composition generally comprises an effective amount of an active agent (e.g., the antibodies or antibody-drug conjugates of the invention) and a pharmaceutically acceptable carrier, diluent or excipient (e.g., a buffer, adjuvant or similar).

[0041] The term effective amount means a dosage or quantity sufficient to produce a desired result. The desired result may comprise an objective or subjective improvement in the recipient of the dosage or amount (e.g., long-term survival, decrease in the number and / or size of tumors, effective prevention of a disease state, etc.).

[0042] A prophylactic treatment is a treatment administered to an individual who does not show signs or symptoms of a disease, pathology or medical disorder, or who shows only early signs or symptoms of a disease, pathology or disorder, such that the treatment is administered for the purpose of decreasing, preventing or reducing the risk of developing the disease, pathology or medical disorder. A prophylactic treatment functions as a preventive treatment against a disease or disorder. A prophylactic activity is an activity of an agent, such as the anti-5T4 bispecific drug-antibody conjugates of the invention, or compositions thereof, which, when administered to an individual who does not show signs or symptoms of a pathology, disease or disorder (or who shows only early signs or symptoms of a pathology, disease or disorder) decreases, prevents or reduces the risk of the individual developing the pathology, disease or disorder.A prophylactically useful agent or compound (e.g., a bispecific anti5T4 drug-antibody conjugate) refers to an agent or compound that is useful in decreasing, preventing, treating, or reducing the development of a pathology, disease, or condition. Petition 870250084408, dated 09 / 19 / 2025, page 26 / 297 15 / 214 disturbance.

[0043] A therapeutic treatment is a treatment administered to an individual exhibiting symptoms or signs of pathology, disease, or disorder, in which the treatment is administered to the individual for the purpose of reducing or eliminating those signs or symptoms of pathology, disease, or disorder. A therapeutic activity is an activity of an agent, such as a drug-antibody conjugate of the invention, or a composition thereof, that eliminates or reduces signs or symptoms of a pathology, disease, or disorder when administered to an individual suffering from such signs or symptoms. A therapeutically effective agent or compound (e.g., a bispecific anti-5T4 drug-antibody conjugate) indicates that an agent or compound is effective in reducing, treating, or eliminating such signs or symptoms of the pathology, disease, or disorder.

[0044] The term "treat cancer," as used herein, unless otherwise indicated, means to reverse, alleviate, inhibit the progress of, or prevent, partially or completely, the growth of tumors, tumor metastases, or other cancerous or neoplastic cells in an individual. The term "treatment," as used herein, unless otherwise indicated, refers to the act of treating.

[0045] The terms identical or percent identity, in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are identical or have a specific percentage of nucleotides or amino acid residues that are the same when compared and aligned for maximum correspondence. To determine percent identity, the sequences are aligned for optimal comparison purposes (e.g., gaps may be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino acid or nucleic acid sequence). Petition 870250084408, dated 09 / 19 / 2025, p. 27 / 297 16 / 214 Amino acid or nucleotide residues at corresponding amino acid or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid or nucleotide residue as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., the % identity equals the number of identical positions / total number of positions (e.g., overlapping positions χ² 100)). In some embodiments, the two sequences have the same length.

[0046] The term substantially identical, in the context of two nucleic acids or polypeptides, refers to two or more sequences or subsequences that have at least 60%, at least 70%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% identity or at least 99% identity (for example, as determined using one of the methods defined below).

[0047] Determining the percentage of identity between two sequences can be done using a mathematical algorithm. A non-limiting example of a mathematical algorithm used for comparing two sequences is the Karlin and Altschul algorithm, 1990, Proc. Natl. Acad. Sci. USA 87:2264-2268, modified as in Karlin and Altschul, 1993, Proc. Natl. Acad. Sci. USA 90:5873-5877. This algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al., 1990, J. Mol. Biol. 215:403-410. BLAST nucleotide searches can be performed with the NBLAST program, score=100, word length=12, to obtain nu sequences. Petition 870250084408, dated 09 / 19 / 2025, page 28 / 297 17 / 214 nucleotides homologous to a nucleic acid encoding a protein of interest. BLAST protein searches can be performed with the XBLAST program, score=50, word length=3, to obtain amino acid sequences homologous to a protein of interest. To obtain gap alignments for comparison purposes, Gapped BLAST can be used as described in Altschul et al., 1997, Nucleic Acids Res. 25:3389-3402. Alternatively, PSI-BLAST can be used to perform an iterated search, which detects distant relationships between molecules (id.). When using the BLAST, Gapped BLAST, and PSI-BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. Another non-limiting example of a mathematical algorithm used for sequence comparison is the Myers-Miller algorithm, CABIOS (1989). This algorithm is incorporated into the ALIGN program (version 2).0), which is part of the GCG sequence alignment software package. When using the ALIGN program to compare amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. Additional algorithms for sequence analysis are known in the art and include ADVANCE and ADAM, as described in Torellis and Robotti, 1994, Comput. Appl. Biosci. 10:3-5; and FASTA, described in Pearson and Lipman, 1988, Proc. Natl. Acad. Sci. USA 85:2444-8. Alternatively, protein sequence alignment can be performed using the CLUSTAL W algorithm, as described by Higgins et al., 1996, Methods Enzymol. 266:383-402.

[0048] As used herein, antigen-binding domain refers to a region in an antibody that binds to antigens. An exemplary antigen-binding domain comprises a constant domain and a variable domain of each of the antibody's heavy and light chains. However, alternative arrangements, such as, for example, dom- Petition 870250084408, dated 09 / 19 / 2025, page 29 / 297 18 / 214 single-domain antigen-binding domains are contemplated as being within the scope of the present invention, provided that such domains are capable of binding to an antigen. Exemplary antigen-binding domains include, but are not limited to, scFv, Fab fragments, Fab' fragments, F(ab')2 fragments and the like, and are described in greater detail below.

[0049] As used herein, the term binds, binds specifically to, or is specific to refers to measurable and reproducible interactions, such as the binding between a target and an antigen-binding domain, which is determinant of the target's presence in the presence of a heterogeneous population of molecules, including biological molecules. For example, an antibody that binds specifically to a target (which may be an epitope) is an antibody that binds to that target with greater affinity, avidity, more readily, and / or for a longer duration than it binds to other targets. In one embodiment, the extent of binding of an antigen-binding domain to an unrelated target is less than about 10% of the antibody binding to the target, as measured, for example, by a radioimmunoassay (RIA). In certain embodiments, an antibody that binds specifically to a target has a dissociation constant (Kd) of < 1 μM, < 100 nM, < 10 nM, < 1 nM, < 0.1 nM, or < 0.01 nM.

[0050] In certain embodiments, an antigen-binding domain binds specifically to an epitope on a protein that is conserved among proteins of different species. In another embodiment, specific binding may include, but does not require, exclusive binding.

[0051] As used in this descriptive report, the singular forms a, an, and the include plural references, unless the context clearly indicates otherwise. The reference to the formulation or the method includes one or more formulations, methods and / or steps of the type described herein and / or which will become apparent to those persons. Petition 870250084408, dated 19 / 09 / 2025, page 30 / 297 19 / 214 those skilled in the art after reading this invention.

[0052] The term polypeptide refers to a polymer of amino acids and their equivalents and does not refer to a specific length of a product; therefore, peptides and proteins are included in the definition of polypeptide. A protein may have one or more polypeptides. Antibodies, as defined herein, are also included in the definition of polypeptides. A polypeptide region refers to a segment of a polypeptide, which segment may contain, for example, one or more domains or motifs (for example, a polypeptide region of an antibody may contain, for example, one or more complementarity-determining regions (CDRs)). The term fragment refers to a portion of a polypeptide that is smaller than the entire polypeptide, as occurs naturally.

[0053] Unless otherwise indicated by the context, a derivative is a polypeptide or fragment thereof having one or more non-conservative or conservative amino acid substitutions with respect to a second polypeptide (also referred to as a variant), or deletions or insertions with respect to it; or a polypeptide or fragment thereof that is modified by covalent attachment to a second molecule, such as, for example, by attachment to a heterologous polypeptide, or by glycosylation, acetylation, phosphorylation and the like. Also included within the definition of derivative are, for example, polypeptides containing one or more analogs of an amino acid (e.g., non-natural amino acids and the like), polypeptides with unsubstituted linkages, as well as other modifications known in the art, both naturally occurring and non-natural.

[0054] An isolated polypeptide is one that has been identified and separated and / or recovered from a component of its natural environment. The contaminating components of its natural environment are ma Petition 870250084408, dated 09 / 19 / 2025, page 31 / 297 20 / 214 materials that would interfere with the diagnostic or therapeutic uses of the polypeptide and may include enzymes, hormones, and other protein or non-protein solutes. An isolated polypeptide includes an isolated antibody, or a fragment or derivative thereof.

[0055] As used herein, the term chimeric antigen receptor (CAR) refers to an artificial transmembrane protein receptor comprising (i) an extracellular domain capable of binding to at least one predetermined CAR ligand or antigen, such as a 5T4 antigen-binding domain as described herein, (ii) an intracellular segment comprising one or more cytoplasmic domains derived from signal transducer proteins other than the polypeptide from which the extracellular domain is derived, and (iii) a transmembrane domain. In some cases, CARs also include a binding domain. CARs can be used to inject artificial specificity into a specific immune effector cell, such as a helper T cell (CD4+), a cytotoxic T cell (CD8+), or an NK cell.Carcinoma receptors (CARs) can be used to confer the specificity of a monoclonal antibody to a T cell, thus enabling the generation of a large number of specific T cells, for example, for use in adoptive cell therapy. Depending on the specific CAR architecture and the intracellular signaling domains employed, the CAR can be an activating receptor or an inhibitory receptor. Exemplary activating CARs comprise an intracellular CD3 zeta domain, one or more intracellular domains for additional costimulatory signaling, such as ICOS, CD137 (4-1BB), CD27, CD28, CD134, CD152 (CTLA-4), CD223 (LAG4), DAP10 and / or OX-40 and, optionally, an extracellular articulation region, for example, derived from CD8a or CD28. Many different CARs are known in the art, all of which are contemplated as being included within the scope of the present invention. Petition 870250084408, dated 09 / 19 / 2025, page 32 / 297 21 / 214

[0056] As used herein, the term bispecific T-cell antibody refers to an antibody with dual binding specificity for a cancer-associated antigen, such as 5T4, and a CD3 subunit present on the surface of T cells, for example, any of the following: CD3 epsilon, CD3 gamma, CD3 delta, or CD3 zeta. Without wishing to be bound to theory, it is believed that this allows the bispecific T-cell antibody to cross-link and bring T cells and cancer cells closer together, inducing T cell activation and subsequent cancer cell death.

[0057] The term about, as used here, means, in quantitative terms, more or less 5%, or in another way, more or less 10%, or in another way, more or less 15%, or in another way, more or less 20%.

[0058] All methods described herein may be carried out in any suitable order unless otherwise indicated or clearly contradicted by the context. The use of any and all examples, or exemplary language (e.g., such as) provided herein, is intended merely to better clarify the invention and does not represent a limitation to the scope of the invention, unless otherwise claimed. No language in the descriptive report should be interpreted as indicating any unclaimed element as essential to the practice of the invention.

[0059] All publications, patents and patent applications mentioned in this descriptive report are incorporated herein by reference to the same extent as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated by reference. 5T4

[0060] An example of a cancer-associated antigen is trophoblast glycoprotein (TPBG), also known as 5T4 antigen. Petition 870250084408, dated 09 / 19 / 2025, page 33 / 297 22 / 214 human (5T4), oncofetal 5T4 antigen, or Wnt-activated inhibitory factor 1 (WAIF1). The human 5T4 antigen is a 72 kDa type I transmembrane glycoprotein expressed in embryonic tissues, such as the placenta, and in various types of solid tumors and carcinomas, including prostate cancer, gastric cancer, and colorectal cancer. See, for example, U.S. Patent No. 7,074,909 or U.S. Patent No. 7,514,546. However, the 5T4 antigen is expressed at low levels or not expressed at all in most healthy adult epithelial tissues. See Woods et al., Biochem. J. (2002) 366, 353-365.

[0061] The expression or overexpression of the 5T4 antigen in various tumor types, particularly ovarian, gastric, and colorectal tumors, is associated with more unfavorable clinical outcomes. Furthermore, overexpression is associated with alterations in cell morphology and motility consistent with tumor invasion. Thus, the 5T4 antigen is believed to play a role in the progression or malignancy of some solid tumors.

[0062] The invention provides antigen-binding domains, as well as antibodies, antibody-drug conjugates and receptors comprising antigen-binding domains that bind to 5T4.

[0063] The invention provides antigen-binding domains useful for targeting cells, such as cancer cells, that express the 5T4 antigen. In some embodiments, the antigen-binding domains are incorporated into a drug-antibody conjugate, which can be used for 5T4-targeted cancer therapy. Exemplary antibody-drug conjugates include biparatopic antibodies that bind to two different 5T4 epitopes, as well as 5T4 drug-antibody conjugates that can bind to a single 5T4 epitope. In some embodiments, the 5T4 drug-antibody conjugate comprises a biparatopic 5T4 antibody and binds to two different 5T4 epitopes. The antibody-drug conjugates described herein may comprise Petition 870250084408, dated 09 / 19 / 2025, page 34 / 297 23 / 214 the 5T4 antigen-binding portion of an anti-5T4 antibody designed in a single-chain form and fused to a chemotherapeutic agent. In some embodiments, the 5T4 drug-antibody conjugate comprises a biparatopic 5T4 antibody, comprising a full-size IgG antibody linked to an scFv.

[0064] The invention provides pharmaceutical compositions comprising antigen-binding domains, antibodies, antibody-drug conjugates and receptors described herein. In some embodiments, the pharmaceutical compositions comprise a biparatopic 5T4 drug-antibody conjugate comprising a first antigen-binding domain that specifically binds to a first 5T4 epitope, a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope, and a chemotherapeutic agent.

[0065] In addition, this invention provides methods for treating diseases or disorders involving cellular expression of the 5T4 antigen, the methods comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition described herein, for example, a pharmaceutical composition comprising a biparatopic 5T4 drug-antibody conjugate comprising a first antigen-binding domain that binds specifically to a first 5T4 epitope, a second antigen-binding domain that binds specifically to a second 5T4 epitope that is not the same as the first 5T4 epitope, and a chemotherapeutic agent.

[0066] The present invention provides antigen-binding domains that bind to human 5T4 antigen. Human 5T4 comprises an amino acid sequence according to Reference Sequence / NCBI NP_001363851.1: MPGGCSRGPA AGDGRLRLAR LALVLLGWVS SSSPTSSASS FSSSAPFLAS AVSAQPPLPD 61 QCPALCECSE AARTVKCVNR NLTEVPTDLP AYVRNLFLTG NQLAVLPAGA FARRPPLAEL Petition: 870250084408, on September 19, 2025, page. 35 / 297 24 / 214 121 AALNLSGSRL DEVRAGAFEH LPSLRQLDLS HNPLADLSPF AFSGSNASVS APSPLVELIL 181 NHIVPPEDER QNRSFEGMVV AALLAGRALQ GLRRLELASN HFLYLPRDVL AQLPSLRHLD 241 LSNNSLVSLT YVSFRNLTHL ESLHLEDNAL KVLHNGTLAE LQGLPHIRVF LDNNPWVCDC 301 HMADMVTWLK ETEVVQGKDR LTCAYPEKMR NRVLLELNSA DLDCDPILPP SLQTSYVFLG 361 IVLALIGAIF LLVLYLNRKG IKKWMHNIRD ACRDHMEGYH YRYEINADPR LTNLSSNSDV (SEQ ID NO: 27).

[0067] Any suitable antigen-binding domain capable of specifically binding to 5T4, or a fragment thereof, is considered within the scope of the present invention, including, but not limited to, a Fab fragment, an F(ab')2 fragment, single-chain variable fragments (scFv), a scab, a dAb, single-domain antibodies (sdAb), such as single-domain VHH antibodies, a single-domain heavy chain antibody or a single-domain light chain antibody, full-size IgG antibodies, antibody fragments, antigen-binding domains or fragments comprising antigen-binding domains, as described in greater detail below. In addition, full-size antibodies, biparatopic antibodies, bispecific T-cell antibodies, fusion proteins and receptors, such as chimeric antigen receptors, described herein, are considered within the scope of the present invention.

[0068] The invention provides antibodies comprising antigen-binding domains specific for the 5T4 antigen described herein. For example, the antibodies may be monoclonal antibodies, such as full-size IgG antibodies.

[0069] As used herein, an antibody refers to a protein comprising one or more polypeptides substantially or partially encoded by immunoglobulin genes or fragments of immunoglobulin genes. Recognized immunoglobulin genes include the constant region genes kappa, lambda, alpha, gamma, delta, epsilon, and mu, as well as a myriad of variable region immunoglobulin genes. Light chains are classified as kappa or Petition 870250084408, dated 09 / 19 / 2025, page 36 / 297 25 / 214 lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes IgG, IgM, IgA, IgD, and IgE, respectively. A typical immunoglobulin structural unit (e.g., antibody) comprises a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having a light chain (approximately 25 kD) and a heavy chain (approximately 50 to 70 kD). The N-terminus of each chain defines a variable region of approximately 100 to 110 or more amino acids, primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chains, respectively. The term antibody includes antibody molecules prepared, expressed, created, or isolated by recombinant means, such as antibodies isolated from a host cell transfected to express the antibody.The term antibody also includes bispecific antibodies (e.g., bispecific T-cell antibodies) or biparatopic antibodies, which may include a heterotetrameric immunoglobulin that can bind to more than one different epitope. Bispecific antibodies are generally described in U.S. Patent Application Publication No. 2010 / 0331527, which is incorporated by reference into this application. The term antibody herein is used in the broadest sense and specifically encompasses intact monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) formed from at least two intact antibodies, and antibody fragments, provided they exhibit the desired biological activity.

[0070] The term antibody also includes one or more fragments of an antibody that retain the ability to bind specifically to an antigen, such as, for example, an antibody-binding portion or domain of an antibody, sometimes referred to herein as a Petition 870250084408, dated 19 / 09 / 2025, page 37 / 297 26 / 214 antigen binding minimum or antigen-binding portion.

[0071] The term antigen-binding domain or antigen-binding region, as used herein, refers to a domain of an antigen-binding portion that is responsible for the specific binding between an antigen-binding portion and an antigen. For example, the antigen-binding region of an antibody or a fragment thereof is formed by amino acid residues of the N-terminal variable regions of the heavy chain (abbreviated herein as VH) and the light chain (abbreviated herein as VL). The variable regions of the VH and VL each comprise three hypervariable regions, termed complementarity-determining regions (CDRs). The 3 CDRs of the VH and the 3 CDRs of the VL are arranged three-dimensionally relative to each other to form an antigen-binding surface.Examples of binding fragments encompassed by the term antigen-binding portion of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CH1 domains; (ii) an F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge in the junction region; (iii) an Fd fragment consisting of the VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment (Ward et al. (1989) Nature 241:544-546), consisting of a VH domain; (vi) an isolated CDR; and (vii) an scFv, consisting of the two domains of the Fv fragment, VL and VH, joined by a synthetic linker to form a single protein chain in which the VL and VH regions pair to form monovalent molecules. Other forms of single-chain antibodies, such as diabodies, are also encompassed by the term antibody (see, for example, Holliger et al.(1993) PNAS USA 90:6444-6448; Poljak et al. (1994) Structure 2:1 121-1 123).

[0072] In addition, an antibody or antigen-binding domain Petition 870250084408, dated 09 / 19 / 2025, page 38 / 297 27 / 214 of the same may be part of a larger immunoadhesion molecule, formed by the covalent or non-covalent association of the antibody or antigen-binding domain with one or more other proteins or peptides. Examples of such immunoadhesion molecules include the use of the central region of streptavidin to produce a tetrameric scFv molecule (Kipriyanov et al. (1995) Human Antibodies and Hybridomas 6:93-101) and the use of a cysteine ​​residue, a marker peptide, and a C-terminal polyhistidine marker to produce bivalent and biotinylated scFv molecules (Kipriyanov et al. (1994) Mol. Immunol. 31: 1047-1058). Antibody fragments, such as Fab and F(ab')2 fragments, can be prepared from whole antibodies using conventional techniques, such as by digestion of whole antibodies with papain or pepsin.Furthermore, antibodies, antibody fragments, and immunoadhesion molecules can be obtained using standard recombinant DNA techniques commonly known in the art (see Sambrook et al., 1989).

[0073] The term human antibody or humanized antibody is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example, in CDRs and, in particular, in CDR3. Humanized forms of non-human antibodies (e.g., murine) are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antibody antigen-binding subsequences) containing a minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (antibody). Petition 870250084408, dated 09 / 19 / 2025, page 39 / 297 28 / 214 receptor) in which residues from a complementarity-determining region (CDR) of the receptor are replaced by residues from a CDR of a non-human species (donor antibody), such as mouse, rat, or rabbit, that exhibit the desired specificity, affinity, and capacity. In some cases, residues from the Fv structure of human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are not found in either the receptor antibody or the imported CDR sequences or structure. These modifications are also made to refine and optimize antibody performance.In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all CDR regions correspond to those of a non-human immunoglobulin and all or substantially all FR regions are those of a human immunoglobulin sequence. The humanized antibody may also comprise at least a portion of an immunoglobulin constant (Fc) region, typically that of a human immunoglobulin.

[0074] The term recombinant human antibody, as used herein, is intended to include all human antibodies that are prepared, expressed, created, or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell, antibodies isolated from a combinatorial library of recombinant human antibodies, antibodies isolated from an animal (e.g., a mouse) transgenic for human immunoglobulin genes, or antibodies prepared, expressed, created, or isolated by any other means involving the splicing of human immunoglobulin gene sequences to other DNA sequences. Such human antibodies re Petition 870250084408, dated 09 / 19 / 2025, page 40 / 297 29 / 214 recombinant antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when a transgenic animal for human Ig sequences is used, to in vivo somatic mutagenesis) and, therefore, the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, although derived from and related to human germline VH and VL sequences, may not naturally exist in the germline repertoire of human antibodies in vivo. The general structure of antibodies is known in the art. Briefly, an immunoglobulin monomer comprises two heavy chains and two light chains connected by disulfide bridges. Each heavy chain is paired with one of the light chains to which it is directly linked via a disulfide bond.Each heavy chain comprises a constant region (which varies depending on the antibody isotype) and a variable region. The variable region comprises three hypervariable regions (or complementarity-determining regions) designated CDRH1, CDRH2, and CDRH3, which are supported by structural regions. Each light chain comprises a constant region and a variable region, with the variable region comprising three hypervariable regions (designated CDRL1, CDRL2, and CDRL3) supported by structural regions in a manner analogous to the variable region of the heavy chain.

[0075] The hypervariable regions of each pair of heavy and light chains cooperate to provide an antigen-binding site capable of binding to a target antigen. The binding specificity of a pair of heavy and light chains is defined by the CDR1, CDR2, and CDR3 sequences of the heavy and light chains. Thus, once a set of CDR sequences (i.e., the CDR1, CDR2, and CDR3 sequences for the heavy and light chains) is Petition 870250084408, dated 09 / 19 / 2025, p. 41 / 297 30 / 214 determined by giving rise to a specific binding specificity, the set of CDR sequences can, in principle, be inserted into the appropriate positions within any other antibody structure regions bound to any constant regions of the antibody, so as to provide a different antibody with the same antigen-binding specificity.

[0076] Antibodies, or antigen-binding domains, exist as intact immunoglobulins or as a series of well-characterized fragments produced by digestion with various peptidases. Thus, for example, pepsin digests an antibody below the disulfide bonds in the junction region to produce F(ab')2, a Fab dimer which, in turn, is a light chain attached to VH-CH1 by a disulfide bond. OF(ab')2 can be reduced under moderate conditions to break the disulfide bond in the junction region, thus converting the F(ab')2 dimer into a Fab' monomer. The Fab' monomer is essentially a Fab with part of the junction region. Although various antibody fragments are defined in terms of the digestion of an intact antibody, the versed will realize that such Fab' fragments, etc., can be synthesized de novo chemically or using recombinant DNA methodology.Thus, the term antibody, as used here, also includes antibody fragments produced by modifying whole antibodies or synthesized de novo using recombinant DNA methodologies.

[0077] Antibodies, or antigen-binding domains, include single-chain antibodies, for example, single-chain Fv antibodies (sFv or scFv), in which a variable heavy chain and a variable light chain are joined (directly or via a peptide linker) to form a continuous polypeptide.

[0078] Antibodies, or antigen-binding domains, include single-domain antibodies, which comprise a fragment of an Petition 870250084408, dated 09 / 19 / 2025, page 42 / 297 31 / 214 A single-domain antibody consisting of a single monomeric variable antibody domain capable of selectively binding to an antigen domain. Examples include, but are not limited to, heavy chain antibodies, naturally light chain-deficient antibodies, single-domain antibodies derived from conventional 4-chain antibodies, engineered antibodies, and single-domain structures other than those derived from antibodies. Single-domain antibodies may be any of the art or any future single-domain antibodies. Single-domain antibodies may be derived from any species, including, but not limited to, mouse, human, camel, llama, goat, rabbit, and bovine.

[0079] As explained above, the antibodies or antigen-binding domains used herein optionally comprise F(ab)2, F(ab')2, Fab, Fab', scFv, single-domain antibodies, etc., depending on the specific requirements of the embodiment. Some embodiments use antibodies comprising IgG domains. However, other embodiments comprise alternative immunoglobulins, such as IgM, IgA, IgD, and IgE. Furthermore, all possible isotypes of the various immunoglobulins are also covered by the present embodiments. Thus, IgG1, IgG2, IgG3, IgG4, etc., are all possible molecules in the antibody domains used in the invention. In addition to the choice of immunoglobulin type and isotype selection, different embodiments of the invention may comprise various articulation regions (or functional equivalents thereof). Such articulation regions provide flexibility between the different antibody domains and, for example, an effector to which the antibody is fused.

[0080] The antibodies or antigen-binding domains of the present invention include chimeric antibodies or antigen-binding domains (immunoglobulins) in which a portion of the heavy and / or light chain is identical or homologous to the corresponding sequences Petition 870250084408, dated 09 / 19 / 2025, p. 43 / 297 32 / 214 teeth in antibodies derived from a specific species or belonging to a specific class or subclass of antibodies, while the remainder of the chains is identical or homologous to the corresponding sequences in 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.

[0081] In some embodiments, the antibodies and antibody-drug conjugates of the present invention comprise a 5T4-specific antigen-binding domain comprising any of the CDRs described in Tables 1-2. Table 1. Heavy chain CDR sequences for 5T4 binding domains No. CDRH1 CDRH2 CDRH3 1 GYSFTDYYMH (SEQ ID NO: 1) RVSPNNGATNTNQK FKD (SEQ ID NO: 2) STMITSYYFDY (SEQ ID NO: 3) 2 GFDFSRYWMT (SEQ ID NO: 4) EINPDSRTINYTPSLK D (SEQ ID NO: 5) PDHDYNPYYFNY (SEQ ID NO: 6) 3 GFDFSRYWMT (SEQ ID NO: 4) EINPDSNTINYTPSLK D (SEQ ID NO: 24) PDYDYNPYYFAY (SEQ ID NO: 40) 4 GFTFSSFGLH (SEQ ID NO: 13) YISVGSSTIYYADPVK G (SEQ ID NO: 25) SRTYYRSEIDS (SEQ ID NO: 41) 5 GFNIKDTYMH (SEQ ID NO: 14) RIDPADGNTKFDPKF QG (SEQ ID NO: 26) FRRYDYVMDY (SEQ ID NO: 42) 6 GYSFTGYYLH (SEQ ID NO: 15) RVNPNNGATVYNQN FKG (SEQ ID NO: 28) SIMITTYDFDY (SEQ ID NO: 43) 7 GYSFTGYYLH (SEQ ID NO: 15) RVNPNNGGTIYNQNF KG (SEQ ID NO: 29) SIMITTFDFDY (SEQ ID NO: 44) 8 GYTFSSYWIE (SEQ ID NO: 16) EILPGSGRTNYNEKF KG (SEQ ID NO: 30) GNYGSSPYYFDY (SEQ ID NO: 45) 9 GYTFTHYVIS (SEQ ID NO: 17) EIYPGSGSTYYNEKF KG (SEQ ID NO: 31) GGRYGFDY (SEQ ID NO: 46) 10 GFSLSTSGVGVD (SEQ ID NO: 18) HIWWDDVKRYNPAL KS (SEQ ID NO: 32) IADGYSAPWFAY (SEQ ID NO: 47) Petition: 870250084408, on September 19, 2025, page. 44 / 297 33 / 214 No. WGDSYRYFDV (SEQ ID NO: 49) 13 GFDFSRYWMT (SEQ ID NO: 4) EINPDSRTINYTPPLK D (SEQ ID NO: 35) PDHEYNPYYFNN (SEQ ID NO: 50) 14 GFDFSRYWMT (SEQ ID NO: 4) EINPDSRTINYTPSLK D (SEQ ID NO: 5) PDHDYNPYYFNY (SEQ ID NO: 6) 15 GFDFSRYWMT (SEQ ID NO: 4) EINPDSRTINYTPSLK D (SEQ ID NO: 5) PDHDYNPYYFNY (SEQ ID NO: 6) 16 GFNIKDTYMH (SEQ ID NO: 14) RIDPANGNTKYDPKF QG (SEQ ID NO: 36) FRRYALVMDY (SEQ ID NO: 51) 17 GYSFTGYYLH (SEQ ID NO: 15) RVNPNNGGTSYNQK FKG (SEQ ID NO: 37) STMITSYYFDY (SEQ ID NO: 3) 18 GYSFTGYYIH (SEQ ID NO: 21) RVNPNNGGTIYNQKF KG (SEQ ID NO: 38) STMITSYYFDY (SEQ ID NO: 3) 19 GYTFSTYWIE (SEQ ID NO: 22) EILPGSGRNNYNEKF KG (SEQ ID NO: 39) GNYGSSPYYFDY (SEQ ID NO: 45) 20 GFSLSTSGMGVG (SEQ ID NO: 23) HIWWDDVKRYNPAL KS (SEQ ID NO: 32) IADGYYAPWFAY (SEQ ID NO: 52) Table 2. CDR sequences of the light chain for 5T4 binding domains No. CDRL1 CDRL2 CDRL3 1 KASQSVSTDVA (SEQ ID NO: 7) FASDRYT (SEQ ID NO: 8) QQDYSSPPT (SEQ ID NO: 9) 2 RPSQSVSTSSNSYI H (SEQ ID NO: 10) YASNLES (SEQ ID NO: 11) QQSWEIPLT (SEQ ID NO: 12) 3 RASQSVSTSRYSYM H (SEQ ID NO: 53) YASNLES (SEQ ID NO: 11) QHSWEIPLT (SEQ ID NO: 76) NO: 55) LASNLES (SEQ ID NO: 68) QQNNEDPWT (SEQ ID NO: 78) Petition 870250084408, dated 09 / 19 / 2025, page 45 / 297 34 / 214 No. CDRL1 CDRL2 CDRL3 6 KASQDVSIDVG (SEQ ID NO: 56) WASTRHT (SEQ ID NO: 69) QQHYSTPPT (SEQ ID NO: 79) 7 KASQDVNTAVV (SEQ ID NO: 57) WASTRHT (SEQ ID NO: 69) QQHYSTPPT (SEQ ID NO: 79) 8 RASQSVSTSRNSYM H (SEQ ID NO: 58) YASNLES (SEQ ID NO: 11) QHSWEIPLT (SEQ ID NO: 76) 9 TASSSVSSSYLH (SEQ ID NO: 59) STSNLAS (SEQ ID NO: 70) HQYHRSPLT (SEQ ID NO: 80) 10 KASQDINKYIA (SEQ ID NO: 60) YTSTLQP (SEQ ID NO: 71) LQCDNLWT (SEQ ID NO: 81) 11 RASQSVSTSSSNSY VH (SEQ ID NO: 61) NASNLES (SEQ ID NO: 72) QHSWEIPYT (SEQ ID NO: 77) 12 SASSSVSFMH (SEQ ID NO: 62) STSNLAS (SEQ ID NO: 70) QQRSGYPPKFT (SEQ ID NO: 82) 13 RPSQSVSTSSNSYI H (SEQ ID NO: 10) YASNLEP (SEQ ID NO: 73) QQSWEIPLT (SEQ ID NO: 12) 14 RPSQSVSTSSNSYI H (SEQ ID NO: 10) YASNLES (SEQ ID NO: 11) QQSWEIPLT (SEQ ID NO: 12) 15 RASQSVSTSRYSYI H (SEQ ID NO: 63) YASNLES (SEQ ID NO: 11) QHSWEIPLT (SEQ ID NO: 76) 16 RASETIDSYGNTFM H (SEQ ID NO: 64) LASNLES (SEQ ID NO: 68) QQNNEDPWT (SEQ ID NO: 78) 17 KASQSVSNDVA (SEQ ID NO: 65) YVSNRYI (SEQ ID NO: 74)QQDYSSPPT (SEQ ID NO: 9) 18 KASQSVNYDVA (SEQ ID NO: 66) YASKRYT (SEQ ID NO: 75) QQDYSSPPT (SEQ ID NO: 9) 19 RASQSVSTSRNSYM H (SEQ ID NO: 58) YASNLES (SEQ ID NO: 11) QHSWEIPLT (SEQ ID NO: 76) 20 KASQDINKYIA (SEQ ID NO: 60) YTSTLQP (SEQ ID NO: 71) LQCDDLWT (SEQ ID NO: 83)

[0082] A person generally versed in the art will understand that each row in Table 1 describes three heavy-chain CDR sequences and each row in Table 2 describes three light-chain CDR sequences, which together can bind to 5T4. Thus, the of Petition 870250084408, dated 09 / 19 / 2025, p. 46 / 297 The 35 / 214 antigen-binding domains of 5T4 described herein will be understood as having, in some embodiments, six CDRs, three for the variable heavy domain and three for the variable light domain, corresponding to the rows in the same positions in Tables 1 and 2, respectively, identified by the numbers on the left. Any combination of CDRs comprising a row of CDRs from Table 1, combined with a row of CDRs from Table 2, is considered within the scope of the 5T4 antibodies of the invention. Furthermore, antibodies, antigen-binding domains, CDRs, and sequences thereof that specifically bind to 5T4 epitopes can be derived by methods known in the art. For example, the monoclonal antibodies to be used here can be produced by the hybridoma method, first described by Kohler et al., 1975, Nature 256:495, or they can be produced by recombinant DNA methods (see, for example, US Patent No. 4,816,567).Monoclonal antibodies can also be isolated from phage antibody libraries using the techniques described in Clackson et al., 1991, Nature 352:624-628 and Marks et al., 1991, J. Mol. Biol. 222:581-597, for example, and the antibody sequences and corresponding coding nucleic acids can be determined by methods known in the art.

[0083] Bispecific antibodies are antibodies that have binding specificities for at least two different antigens. Biparatropic antibodies are antibodies that bind to two distinct epitopes of the same antigen. Both bispecific antibodies, for example, antibodies that bind to 5T4 using a 5T4 antigen-binding domain, as described herein, and that also bind to an additional antigen, and biparatropic antibodies that bind to 5T4, are contemplated as being included within the scope of the present invention. Petition 870250084408, dated 09 / 19 / 2025, page 47 / 297 36 / 214

[0084] The present invention provides biparatopic antibody-drug conjugates having a first antigen-binding domain that binds to a first 5T4 epitope and a second antigen-binding domain that binds to a second 5T4 epitope that is not the same as the first 5T4 epitope, wherein the first antigen-binding domain is operably linked to the second antigen-binding domain. In some embodiments, the first antigen-binding domain is linked to the second antigen-binding domain by means of a linker.

[0085] Antibodies with more than two valences are also contemplated as being included within the scope of the invention. For example, trispecific antibodies can be prepared. See, Tutt et al., J. Immunol. 147:60 (1991).

[0086] In some respects, the first and second antigen-binding domains are selected independently of the group consisting of a Fab fragment, an F(ab')2 fragment, an scFv, a scab, a dAb, a single-domain heavy chain antibody, a single-domain light chain antibody, and a natural-size IgG antibody.

[0087] In some aspects, the biparatopic antibodies of the invention comprise a first antibody comprising a full-size IgG antibody comprising a first antigen-binding domain. In some aspects, the second antigen-binding domain comprises a scFv. In some aspects, the drug-antibody conjugate is tetravalent for binding to a 5T4 antigen.

[0088] In some respects, the biparatopic 5T4 antibodies described herein comprise a scFv. In some embodiments, the antibody-drug conjugate comprises two scFv that bind specifically to a 5T4 epitope. In some respects, the scFv comprises Petition 870250084408, dated 09 / 19 / 2025, p. 48 / 297 37 / 214 a heavy chain and a light chain, in which the C-terminal of the light chain is operably linked to the N-terminal of the heavy chain by means of a linker, or the C-terminal of the heavy chain is operably linked to the N-terminal of the light chain by means of a linker. In some embodiments, the linker comprises a sequence of SEQ ID NO: 153.

[0089] In some aspects, biparatopic antibodies comprise a scFv and a natural-sized IgG antibody. In some embodiments, the N-terminal of the scFv is operably linked to the C-terminal of a heavy chain of the natural-sized IgG antibody. In some aspects, the C-terminal of the ScFv is operably linked to the N-terminal of a heavy chain of the natural-sized IgG antibody.

[0090] In some respects, scFv is operably linked to the full-size IgG antibody heavy chain using a linker. In some respects, the linker comprises or consists of an amino acid sequence of SEQ ID NO: 152.

[0091] In some aspects of the biparatopic drug-antibody conjugates described herein, the biparatopic antibody comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprising an scFv, and the antibody-drug conjugate comprises four polypeptides comprising two polypeptides comprising, from the N-terminal to the C-terminal, the heavy chain of the full-size IgG antibody, a linker and the second antigen-binding domain; and two polypeptides comprising the light chain of the full-size IgG antibody.

[0092] In some aspects of antibody-drug conjugates, the antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain. Petition 870250084408, dated 09 / 19 / 2025, page 49 / 297 38 / 214 and the second antigen-binding domain comprises an scFv, and the antibody-drug conjugate comprises four polypeptides comprising two polypeptides comprising, from the N-terminal to the C-terminal, the second antigen-binding domain, a ligand and the full-size IgG antibody heavy chain; and two polypeptides comprising the full-size IgG antibody light chain.

[0093] As used herein, binding affinity refers to the tendency of one molecule to bind (typically non-covalently) to another molecule, such as the tendency of one member of a specific binding pair to another member of a specific binding pair. A binding affinity can be measured as a dissociation constant, which for a specific binding pair (such as an antibody / antigen pair) can be less than 1 χ 10-5M, less than 1 χ 10-6M, less than 1 χ 10-7M, less than 1 χ 10-8M, less than 1 χ 10-9M, less than 1 χ 10-10M, less than 1 χ 10-11M, or less than 1 χ 10-12M. In one aspect, binding affinity is calculated by a modification of the Scatchard method described by Frankel et al., Mol. Immunol., 16:101-106, 1979. In another aspect, binding affinity is measured by a binding constant. In yet another aspect, binding affinity is measured by an antigen / antibody dissociation rate.In yet another aspect, a high binding affinity is measured by a competitive radioimmunoassay.

[0094] The term dissociation constant, or KD(M), as used herein, refers to the dissociation equilibrium constant of a specific antibody-antigen interaction. In one aspect, KD is determined, for example, by surface plasmon resonance (SPR) technology on a BIAcore 8000 instrument, using the antigen as the ligand and the antibody as the analyte. In some aspects, the antibody binds to the predetermined antigen with a color affinity. Petition 870250084408, dated 09 / 19 / 2025, page 50 / 297 39 / 214 responding to a KD that is at least ten times smaller, such as at least 100 times smaller, for example, at least 1,000 times smaller, such as at least 10,000 times smaller, for example, at least 100,000 times smaller, than its affinity to bind to a non-specific antigen (e.g., BSA, casein) other than the predetermined antigen or a closely related antigen. The amount by which the affinity is smaller is dependent on the antibody's KD, so that when the antibody's KD is very low (i.e., the antibody is highly specific), then the amount by which the affinity for the antigen is smaller than the affinity for a non-specific antigen can be at least 10,000 times larger.

[0095] In some respects, the equilibrium dissociation constant (KD) of the antigen-binding domain for 5T4 binding is between about 1 x 10-12 and about 1 x 10-7M, about 1 x 10-12 and about 1 x 10-8M, about 1 x 10-12 and about 1 x 10-9M, about 1 x 10-11 and about 1 x 10-9M, or about 1 x 10-11 and about 9 x 10-10M. In some respects, the KD of the antigen-binding domain for 5T4 binding is between about 7.42 x 10-11 and about 7.75 x 10-10M. In some aspects, the KD is less than or equal to 7.75 x 10⁻¹⁰M, for example, less than or equal to 3.20 x 10⁻¹⁰M, less than or equal to 1.98 x 10¹⁰M, or less than or equal to 7.42 x 10⁻¹¹M. In some aspects, the KD for 5T4 binding is between approximately 3.63 x 10⁻¹² and approximately 1.43 x 10⁹M. In some aspects, the KD for 5T4 binding is between approximately 3.63 x 10⁻¹² and approximately 1.34 x 10⁻⁹M. In some aspects, the KD of the antigen-binding domain for 5T4 binding is between approximately 3.63 x 10⁻¹² and approximately 1.59 x 10⁻¹¹M.In some respects, the KD for 5T4 linkage is between approximately 7.42 x 10-11 and approximately 7.75 x 10-10M. In some respects, the KD for 5T4 linkage is between approximately 7.42 x 10-11 and approximately 7.75 x 10-10M.

[0096] In some aspects of biparatopic or conju antibodies Petition 870250084408, dated 09 / 19 / 2025, p. 51 / 297 40 / 214 biparatopic antibody-drug compounds described herein, the equilibrium dissociation constant (KD) for 5T4 binding of at least one of the first antigen-binding domains or the second antigen-binding domain is between about 1 x 10-12e about 1 x 10-7M, about 1 x 10-12e about 1 x 10-8M, about 1 x 10-12e about 1 x 10-9M, about 1 x 10-11e about 1 x 10-9M, or about 1 x 10-11e about 9 x 10-10M. In some respects, the KD for 5T4 binding of at least one of the first antigen-binding domains or of the second antigen-binding domain is between approximately 7.42 x 10-11 and approximately 7.75 x 10-10M. In some respects, the KD for 5T4 binding of at least one of the first antigen-binding domains or of the second antigen-binding domain is between approximately 3.63 x 10-12 and approximately 7.75 x 10-10M.In some respects, the KD is less than or equal to 7.75 x 10⁻¹⁰M, for example, less than or equal to 3.20 x 10⁻¹⁰M, less than or equal to 1.98 x 10⁻¹⁰M, or less than or equal to 7.42 x 10⁻¹¹M. In some respects, the KD for 5T4 binding of the first antibody or antigen-binding domain is between approximately 7.42 x 10⁻¹¹ and approximately 7.75 x 10⁻¹⁰M. In some respects, the KD of the first antibody or antigen-binding domain for 5T4 binding is between approximately 3.63 x 10⁻¹² and approximately 1.43 x 10⁻⁹M. In some respects, the KD of the first antibody or antigen-binding domain is between approximately 3.63 x 10⁻¹² and approximately 1.34 x 10⁻⁹M. In some respects, the KD of the first antibody or antigen-binding domain is between approximately 3.63 x 10-12 and approximately 1.59 x 10-11M. In some respects, the KD for 5T4 binding of at least the second antibody or antigen-binding domain is between approximately 7.42 x 10-11 and approximately 7.75 x 10-10M.In some respects, the KD of the second antibody or antigen-binding domain for 5T4 binding is between approximately 3.63 x 10⁻¹² and approximately 1.43 x 10⁻⁹ M. In some respects, the KD of the second antibody or antigen-binding domain is... Petition 870250084408, dated 09 / 19 / 2025, page 52 / 297 41 / 214 is between approximately 3.63 x 10⁻¹² and approximately 1.34 x 10⁻⁹M. In some aspects, the KD of the second antibody or antigen-binding domain is between approximately 3.63 x 10⁻¹² and approximately 1.59 x 10⁻¹¹M. In some aspects, the KD for 5T4 binding of the first antibody or antigen-binding domain and the at least second antibody or antigen-binding domain is between approximately 7.42 x 10⁻¹¹ and approximately 7.75 x 10⁻¹⁰M. In some aspects, the KD is between approximately 3.63 x 10⁻¹² and approximately 7.75 x 10⁻¹⁰M. In some aspects, the KD is between approximately 3.63 x 10⁻¹² and approximately 1.59 x 10⁻¹¹M.

[0097] In some respects, the equilibrium dissociation constant (KD) for the binding of an antibody comprising the antigen-binding domain to the Fc gamma I receptor is less than or equal to about 1.0 x 10⁻⁷ M, for example, less than or equal to about 5.0 x 10⁻⁸ M, less than or equal to about 4.0 x 10⁻⁸ M, less than or equal to about 3.0 x 10⁻⁸ M, less than or equal to about 1.0 x 10⁻⁸ M, less than or equal to about 5.0 x 10⁻⁹ M, or less than or equal to about 1.0 x 10⁻⁹ M. In some respects, KD is less than or equal to about 3.96 x 10⁻⁸ M. In some respects, KD is less than 3.73 x 10⁻⁹ M.

[0098] In some respects, the KD for binding to the Fc gamma IIa receptor of an antibody comprising the antigen-binding domain is less than or equal to about 3.74 x 10-6M, for example, less than or equal to about 5.0 x 10-7M, less than or equal to about 1.0 x 10-7M, less than or equal to about 9.86 x 10-8M, less than or equal to about 9.15 x 10-8M, less than or equal to about 5.0 x 10-8M or less than or equal to about 1.0 x 10-8M. In some respects, the KD for binding to the Fc gamma IIa receptor of the antibody comprising the antigen-binding domain is less than or equal to about 9.15 x 10-8M. In some respects, the KD for binding to the Fc gamma IIa receptor is less than or equal to approximately 9.86 x 10-8M.

[0099] In some respects, KD for binding to the Fc receptor ga Petition 870250084408, dated 09 / 19 / 2025, p. 53 / 297 The KD of an antibody comprising the antigen-binding domain is less than or equal to about 2.0 x 10⁻⁷ M, for example, less than or equal to about 1.16 x 10⁻⁷ M, less than or equal to about 1.11 x 10⁻⁷ M, less than or equal to about 1.0 x 10⁻⁷ M, less than or equal to about 5.0 x 10⁻⁸ M, less than or equal to about 1.0 x 10⁻⁸ M, or less than or equal to about 5.0 x 10⁻⁹ M. In some respects, the KD for binding to the Fc gamma IIb receptor is less than or equal to about 1.16 x 10⁻⁷ M. In some respects, the KD for binding to the Fc gamma IIb receptor is less than or equal to about 1.11 x 10⁻⁷ M.

[00100] In some respects, the KD for Fc gamma IIIa receptor binding of an antibody comprising the antigen-binding domain is less than or equal to about 6.0 x 10⁻⁷ M, for example, less than or equal to about 1.0 x 10⁻⁷ M, less than or equal to about 7.0 x 10⁻⁸ M, less than or equal to about 5.05 x 10⁻⁸ M, less than or equal to about 5.0 x 10⁻⁸ M, less than or equal to about 1.0 x 10⁻⁸ M, or less than or equal to about 5.0 x 10⁻⁹ M. In some respects, the KD for Fc gamma IIIa receptor binding is less than or equal to about 6.0 x 10⁻⁸ M. In some respects, the KD for Fc gamma IIIa receptor binding is less than or equal to about 5.05 x 10⁻⁸ M. In some respects, the antibody does not bind detectably to the Fc gamma IIIa receptor.

[00101] In some respects, the antibody comprising the antigen-binding domain does not bind detectably to the Fc gamma IIIb receptor.

[00102] In some respects, the equilibrium dissociation constant (KD) for the binding of an antibody comprising at least one of the first and / or second antigen-binding domains to the Fc gamma I receptor is less than or equal to about 1.0 x 10⁻⁷ M, for example, less than or equal to about 5.0 x 10⁻⁸ M, less than or equal to about 4.0 x 10⁻⁸ M, less than or equal to about 3.0 x 10⁻⁸ M, less than or equal to about 1.0 x 10⁻⁸ M, less than or equal to about 5.0 x 10⁻⁹ M or Petition 870250084408, dated 09 / 19 / 2025, p. 54 / 297 43 / 214 less than or equal to approximately 1.0 x 10⁻⁹M. In some aspects, KD is less than or equal to approximately 3.96 x 10⁻⁸M. In some aspects, KD is less than 3.73 x 10⁻⁹M.

[00103] In some respects, the KD for binding to the Fc gamma IIa receptor of an antibody comprising at least one of the first and / or second antigen-binding domains is less than or equal to about 3.74 x 10-6M, for example, less than or equal to about 5.0 x 10-7M, less than or equal to about 1.0 x 10-7M, less than or equal to about 9.86 x 10-8M, less than or equal to about 9.15 x 10-8M, less than or equal to about 5.0 x 10-8M or less than or equal to about 1.0 x 10-8M. In some respects, the KD for binding to the Fc gamma IIa receptor is less than or equal to about 9.15 x 10-8M. In some respects, the KD for binding to the Fc gamma IIa receptor is less than or equal to approximately 9.86 x 10⁻⁸ M. In some respects, the KD for binding to the Fc gamma IIb receptor is less than or equal to approximately 1.16 x 10⁻⁷ M.

[00104] In some respects, the KD for binding to the Fc gamma IIb receptor of an antibody comprising at least one of the first and / or second antigen-binding domains is less than or equal to about 2.0 x 10-7M, for example, less than or equal to about 1.16 x 10-7M, less than or equal to about 1.11 x 10-7M, less than or equal to about 1.0 x 10-7M, less than or equal to about 5.0 x 10-8M, less than or equal to about 1.0 x 10-8M or less than or equal to about 5.0 x 10-9M. In some respects, the KD for binding to the Fc gamma IIb receptor is less than or equal to about 1.16 x 10-7M. In some respects, the KD for binding to the Fc gamma IIb receptor is less than or equal to approximately 1.11 x 10-7M.

[00105] In some respects, the KD for binding to the Fc gamma IIIa receptor of an antibody comprising at least one of the first and / or second antigen-binding domains is less than or equal to about 6.0 x 10-7M, for example, less than or equal to about 1.0 x 10-7M, less than or equal to about 7.0 x 10-8M, less than or equal to about Petition 870250084408, dated 09 / 19 / 2025, p. 55 / 297 44 / 214 5.05 x 10⁻⁸ M, less than or equal to about 5.0 x 10⁻⁸ M, less than or equal to about 1.0 x 10⁻⁸ M, or less than or equal to about 5.0 x 10⁻⁹ M. In some aspects, the KD for binding to the Fc gamma IIIa receptor is less than or equal to about 6.0 x 10⁻⁸ M. In some aspects, the KD for binding to the Fc gamma IIIa receptor is less than or equal to about 5.05 x 10⁻⁸ M. In some aspects, the antibody does not bind detectably to the Fc gamma IIIa receptor.

[00106] In some respects, the antibody comprising at least one of the first and / or second antigen-binding domains does not bind detectably to the Fc gamma IIIb receptor.

[00107] In some respects, the first and second antibodies bind to different 5T4 molecules on the surface of different cancer cells. In some respects, the first and second antibodies bind to different 5T4 molecules on the surface of the same cancer cell. In some respects, the first and second antibodies bind to the same 5T4 molecule on the surface of a cancer cell. In some respects, the first and second 5T4 epitopes are non-overlapping epitopes. Effector Function of Fc

[00108] In some embodiments, site mutations in the Fc region of antibody-drug conjugates attenuate potential side effects caused by the antibody's effector function, for example, at least the binding affinity to Fc gamma receptors (FcyRs). Without wishing to be bound by theory, it is believed that binding to Fc gamma receptors may induce activating or inhibitory pathways of the immune system, such as, for example, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).

[00109] In some embodiments, the antibody-drug conjugates described herein comprise a size IgG antibody Petition 870250084408, dated 09 / 19 / 2025, p. 56 / 297 45 / 214 natural. In some embodiments, the natural-sized IgG antibody comprises a constant region (Fc) domain. In some embodiments, for example, those in which the antibody-drug conjugate comprises an IgG Fc domain, the Fc domain is a constant region domain of the IgG1 isotype. In some embodiments, the IgG1 constant region domain comprises at least one mutation that reduces effector function, prolongs half-life, or a combination thereof. In some embodiments, the antibody-drug conjugates described herein comprise Fc mutations that reduce binding affinity to Fc gamma receptors. In some embodiments, the Fc mutations reduce binding affinity to an Fc gamma receptor that includes FcyRI. In some embodiments, the Fc mutations reduce binding affinity to an Fc gamma receptor that includes FcyRII. In some embodiments, the Fc mutations reduce binding affinity to an Fc gamma receptor that includes FcyRIII.In some embodiments, the Fc mutation of the drug-antibody conjugate reduces the binding affinity to FcyRI compared to a 5T4 antibody without Fc mutations. In some embodiments, at least one mutation comprises an F at position 237 relative to SEQ ID NO: 100 (L234F), a C or A at position 242 relative to SEQ ID NO: 100 (S239C / A), or a combination thereof.

[00110] In some forms, mutations in the Fc site that reduce binding affinity to FcyRI include L234F and S239C, or S239A.

[00111] In some embodiments, the Fc domain may be a constant region domain of the IgG1 isotype. In some embodiments, the IgG1 constant region domain comprises at least one mutation that reduces effector function, prolongs half-life, or a combination thereof. In some embodiments, mutations in the IgG1 constant region domain prolong the half-life of the conjugate. Petition 870250084408, dated 09 / 19 / 2025, p. 57 / 297 46 / 214 of the drug-antibody conjugate. Fc mutations of the drug-antibody conjugate can prolong the half-life of the drug-antibody conjugate. In some embodiments, at least one mutation comprises a mutation at position 437 relative to SEQ ID NO: 100 (N434). In some embodiments, at least one mutation, where the mutation comprises an A at position 437 relative to SEQ ID NO: 100 (N434A). These amino acids are shown in bold and underlined in Table 5 below. In some embodiments, the antibody-drug conjugate comprises at least one mutation that prolongs the half-life of the drug-antibody conjugate, wherein at least one mutation comprises a mutation at position 437, wherein the mutation also comprises an A at position 437 relative to SEQ ID NO: 100 (N434A).In some embodiments, the antibody-drug conjugate comprises a mutation that prolongs the half-life of the drug-antibody conjugate, wherein the mutation comprises a mutation at position 437, wherein the mutation also comprises an A at position 437 relative to SEQ ID NO: 100 (N434A). In some embodiments, the antibody-drug conjugate comprises a mutation that prolongs the half-life of the drug-antibody conjugate, wherein the mutation comprises a mutation at position 437, wherein the mutation also comprises an A at position 437 relative to SEQ ID NO: 100 (N434A). Table 3. Summary of Equilibrium Dissociation Constants (KD) for binding of exemplary antibody-drug conjugates to selected Fc gamma receptors (FcyRs). Fc receptor KD 5T4-Bs3- FCA Ab1 parental without mutations Fc FcyRI 3.96E-08 3.73E-09 FcyRIIa 9.15E-08 9.86E-08 FcyRIIb 1.16E-07 1.11E-07 Petition 870250084408, dated 09 / 19 / 2025, p. 58 / 297 47 / 214 Fc KD receptor 5T4-Bs3- FCA Ab1 parental without mutations Fc FcyRII^ No binding 5.05E-08 FcyRII^ No binding No binding

[00112] In some respects, the antibody-drug conjugates described herein comprise monoclonal antibodies. In some respects, the monoclonal antibody binds to only a single 5T4 epitope. In some respects, the monoclonal antibody comprises only a first antibody, i.e., it is not a bispecific antibody. In some respects, the monoclonal antibody binds to only a single epitope, i.e., it is not a biparatopic antibody.

[00113] In some respects, the antibodies described herein are bispecific or biparatopic monoclonal antibodies. In some respects, the antibodies comprise a first antigen-binding domain, for example, an scFv, and a second antigen-binding domain, for example, a full-size IgG antibody. In some respects, the antibodies comprise a first antigen-binding domain that binds to a first 5T4 epitope and a second antigen-binding domain that binds to a second 5T4 epitope.

[00114] In some respects, antibodies comprise a first antigen-binding domain that binds to a 5T4 epitope and a second antigen-binding domain that binds to a second antigen, for example, an antigen expressed by cancer cells. Suitable cancer antigens and antigen-binding domains that bind to these antigens will be known to persons skilled in the art and include, for example, B-cell maturation antigen (BCMA), CD19 molecule (CD19), CD20, CD30, CD33, CD38, CD44, CD123, CD138, cell adhesion molecule (CEA), C-type lectin domain family 12 member A (CLEC12A), chorionic somatomammotropin hormone 1 (CS-1), re Petition 870250084408, dated 09 / 19 / 2025, page 59 / 297 48 / 214 epidermal growth factor receptor (EGFR), EGFRvIll, epithelial cell adhesion molecule (EPCAM), canonical delta-type Notch ligand 3 (DLL3), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), mesothelin (MSLN), programmed death ligand 1 (PD-L1), folate receptor alpha (FOLR1), folate receptor gamma (FOLR3), erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2), HER3, bone marrow stromal cell antigen 2 (HM1.24), sperm mitochondria-associated cysteine-rich protein (MCSP), and prostate-specific membrane antigen (PSMA). Alternatively, the bispecific antibodies described here are bispecific T-cell antibodies (TCBs). In these cases, the second antigen is expressed by T cells, for example, a CD3e antigen, and the bispecific antibodies described here assist in the recruitment and engagement of T cells in the presence of 5T4-positive cancer cells.

[00115] In some embodiments, the antigen-binding domains of the present invention comprise a 5T4-specific antigen-binding domain comprising any of the CDRs described in Tables 1-2. Exemplary variable heavy and light chains of the antigen-binding domains of the invention incorporating the CDRs described in Tables 1-2 are provided in Table 4 below. Table 4. Anti-5T4 Heavy and Light Chain Sequences Ab Amino acid sequence Nucleotide sequence VH-1 (Heavy Variable) QVQLVQSGAEVKKPGASV KVSCKASGYSFTDYYMH WVRQAPGQGLEWMGRV SPNNGATNTNQKFKDRVT MTRDTSISTAYMELRSLRS EDTAVYYCARSTMITSYYF DYWGQGTLVTVSS (SEQ ID NO: 96) CAGGTTCAGCTGGTACAG AGCGGAGCTGAAGTCAAG AAACCTGGGGCTTCAGTG AAGGTTAGCTGCAAAGCC TCTGGCTACAGCTTCACA GACTACTACATGCACTGG GTTAGACAGGCACCAGGA CAAGGGCTTGAGTGGATG Petition 870250084408, dated 09 / 19 / 2025, p. 60 / 297 49 / 214 Ab Amino Acid Sequence Nucleotide Sequence GGTCGAGTGTCTCCCAAC AATGGAGCCACCAATACC AACCAGAAGTTCAAGGAT CGTGTCACCATGACTCGG GATACCTCCA1 1 1 CCACTG CCTATATGGAACTGCGCT CCTTGAGGAGTGAGGAGGAGTCAGGTTCA CTAGGAGTACCATGATAA CGTCCTATTACTTCGACTA TTGGGGCCAAGGTACTCT GGTGACAGTGTCTAGC (SEQ ID NO: 14 4) VH-2 EVQLLESGGGLVQPGGSL RLSCAASGFDFSRYWMT WVRQAPGKCLEWVSEINP DSRTICKDRY TAVYYCARPDHDYNPYYF NYWGQGTTVTVSS (SEQ ID NO: 97) GAGGTGCAGCTGCTGGAA TCTGGCGGAGGATTGGTT CAGCCTGGCGGCTCTCTG AGACTGTCTTGTGCCGCC TCTGGCTTCGACTTCTCCC GGTATTGGATGACCTCGCCGGCCGGCC AGTGTCTGGAATGGGTGT CCGAGATCAACCCCGACA GCCGGACCATCAACTACA CCCCTAGCCTGAAGGACC GGTTCACCATCTCCAGAG ACAACGCCAAGAACACCC TGTACCTGCAGATGAACT CCCTGAGAGCCGAGGACA CCGCCGTGTTACTGGTG CTACTGGGGCCAGGGCAC CACCGTGACAG11 1 CTAG C (SEQ ID NO : 145) Petition 870250084408, of 19 / 09 / 2025, p. 61 / 297 50 / 214 Ab Amino Acid Sequence Nucleotide Sequence VL-1 DIVMTQSPSFLSVSVGDR VTITCKASQSVSTDVAWY QQKPGQAPKLLIYFASDR YTGVPRDRFSGSGSGTDFT FTISSLQAEDVAVYYCQQ DYSSPPTFGSEGGTKLE: ID NO: 98) GACATCGTGATGACACAG TCACCCTCC 1 1 1 CTGAGTG TGAGTGTTGGGGATAGAG TCACCATCACATGCAAAG CCAGCCAATCAGTCAGCA CCGATGTAGCCTGGTATC AGCAGAAACCAGGCCAAG CTCCCAAGCTGCTGATCT ACTTCCGCAAGCAAGGTCGACTGTC GGIIIICTGGGTCTGGAT CTGGTACTGACTTCACCTT CACGATCTCCAGTCTGCA GGCTGAAGATGTTGCCGT CTACTACTGTCAGCAGGA CTATTCCTCTCCTCCTACC III GGAGGAGGCACTAAG CTGGAGATAAAGC (SEQ ID NO: 146) VL-2 DIVLAASLAVLTQSLQSLG TISCRPSQSVSTSSNSYIH WYQQKPGQPPKLLIKYAS NLESGVPARFSGSGSGTD FTLTISPVEAEDTATYYCQ QSWEIPLTFGCGTKLEIK (SEQ ID NO: 99) GAIAICGIGCIGACCCAG ICICCIGCCAGCCIGGCI GIIICICIGGAGACCAGCCAGCCAGCCGCI CCIICICAGICCGIGICC ACCICCCAACICCIACA ICCACIGGIAICAGCAGA AGCCCGGCCAGCCICCIA AGCTGCTGATTAAGTACG CCICCAACCIGGAAAICCG GCGIGCCAGCCAGAIIII CCGGCICIGGCICIGGCA ACIGCCAGCAGICCIGGGAGAICCCICIGACCIIIG Petition 870250084408, dated 09 / 19 / 2025, p. 62 / 297 51 / 214 Ab Amino Acid Sequence Nucleotide Sequence GCTGTGGCACCAAGCTGG AAATCAAA (SEQ ID NO: 147) constant HC ASTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFP AVLQSSGLYSLSSTVPSTVKGTTVKTVHNTV NTKVDKRVEPKSCDKTHT CPPCPAPEFLGGPCVFLF PPKPKDTLMISRTPEVTCV VVDVSHEDPEWKFNWYV DGVEVHNACTKPREEQYN STYRVVSVLTVLHQDWLN GKEYKCKVSNCALPAPIEK TIQPPPREQPREEQYTL SREEMTKNQVSLTCLVKG FYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFS CSVMHEALHAHYTQKSLS LSPGK (SEQ ID NO: 148) GCGTCGACAAAGGGCCCC TCCGTG 1 CAGCTAC 1GCCTGACTGACTGACTGCT CTGGAGGAACAGCCGCTC TGGGATGTCTGGTGAAGG ATTACTTCCCTGAGCCAGT GACCGTGAGCTGGAACTC TGGCGCCCTGACCTCCGG AGTGCATACA1 1 1 CCCGCT GTGCTGCAGTCCAGCGGC CTGTATAGCCTGTCTTCCG TGGTGACCGTCCTCGCCGCCG CATACATCTGCAACGTGAA TCACAAGCCCTCCAATACA AAGGTGGACAAGAGAGTG GAGCCTAAGAGCTGTGAT AAGACCCATACATGCCCA CCATGTCCAGCTCCTGAG TTCCTGGGAGGACCTTGC GTGTTCCTG111CCTCCAA AGCCAAAGGACACCCTGATCTCCCTT AGGTGACATGCGTGGTGG TGGACGTGTCCCACGAGG ATCCAGAGGTGAAGTTCAACTGGTACGTGGATGGCG TGGAGGTGCATAATGCTA AGACCAAGCCTAGGGAGG AGCAGTACAACAGCACCT ATCGGGTGGTGTCTGTGC TGACAGTGCTGCACCAGG ACTGGCTGAACGGCAAGG Petition 870250084408, dated 09 / 19 / 2025, page 63 / 297 52 / 214 Ab Amino Acid Sequence Nucleotide Sequence AGTACAAGTGCAAGGTGA GCAATAAGGCCCTGCCAG CTCCCATCGAGAAGACCA TCTCTAAGGCCAAGGGCC AGC CCAGAGAGCCTCAGGTGT ACCCATCTGACATCGCTG TGGAGTGGGAGTCCAATG GCCAGCCCGAGAACAATT ATAAGACCACACCACCCG TGCTGGACTCCGATGGCA GCTTC1 1 1 CTGTACTCCAA GCTGACCGTGGATAAGAG CAGGTGGCAGCAGGGCAA CGTG I III CCTGCCGTGCCGCCGAGCCAG CGCTCATTATACACAGAAA TCTCTGTCCCTGAGCCCA GGCAAG (SEQ ID NO: 150) constant LC RTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQE SVTEQDSKDSTYSLSSTLT LSKADYEKHKVLSEKVTGNRCEVCQGGVTCSFQ NO: 149) GTACGGTGGCCGCTCCAT CCGTGTTCATC III CCACC CTCCGACGAGCAGCTGAA GICCGGAACCGCIAGCGI GGIGIGCCIGCIGAACAA CIICIACCCAAGAGAGGC CAAGGIGCAGIGGAAGGI GGAIAACGCICIGCAGAG CGGCAAIICAGGACCAGGACCAGGACCAGGACCAGGACCAGGCCGACCAGG CIGACCIACCCIGACA CIGICCAAGGCCGAIIAC Petition 870250084408, of 19 / 09 / 2025, p. 64 / 297 53 / 214 Ab Amino acid sequence Nucleotide sequence GAGAAGCACAAGGTGTAT GCTTGCGAGGTGACCCAT CAGGGCCTGTCCAGCCCC GTGACAAAGAGCTTCAAC CGCGGCGAGTGT (SEQ ID NO: 151) Ligand-1 GGGGSGGGGSGGGGS (SEQ ID NO: 152) GGTGGAGGGGGATCcGGC GGCGGCGGCAGTGGCGG AGGAGGCTCC (SEQ ID NO: 154) Ligand-2 GGGGSGGGGSGGGGSG GGGS (SEQ ID NO: 153) GGCGGAGGTGGAAGCGG AGGCGGAGGTAGTGGTG GTGGCGGATCTGGTGGCG GTGGATCT (SEQ ID NO: 155)

[00116] Exemplary full-size heavy and light chains of the antigen-binding domains of the present invention are provided in Table 5 below (HC: heavy chain; LC: light chain). In Table 5, the heavy chain of the complete sequence of the first antibody, a full-size IgG1 antibody, is in italics, with mutations in the constant region underlined. The first linker is underlined, and the VH and VL sequences of the second antibody, an scFv, are in bold and joined by a linker that is in italics and underlined. Table 5. Complete Amino Acid Sequences of the Anti-5T4 Heavy and Light Chain Ab Amino Acid Sequence Nucleotide Sequence HC1 Natural Size Heavy Chain QVQLVQSGAEVKKPGASVK VSCKASGYSFTDYYMHWV RQAPGQGLEWMGRVSPNN GATNTNQKFKDRVTMTRDT SISTAYMELRSLRSEDTAVY YCARSTMITSYYFDYWGQG CAGGTTCAGCTGGTACAG AGCGGAGCTGAAGTCAAG AAACCTGGGGCTTCAGTG AAGGTTAGCTGCAAAGCCT CTGGCTACAGCTTCACAGA CTACTACATGCACTGGGTT Petition 870250084408, dated 09 / 19 / 2025, p. 65 / 297 54 / 214 Ab Amino Acid Sequence Nucleotide Sequence TLVTVSS ASTKGPSVFPLAP SSKSTSGGTAALGCLVKDY FPEPVTVS WNSGAL TSG VH TFPA VLQSSGL YSLSSVVTV PSSSLGTQTYICNVNHKPSN TKVDKRTKVTCVTCCPK PCPAPEFLGGPCVFLFPPKP KDTLMISRTPEVTCVVVDVS HEDPEVKFNWYVDG VEVH NAKTKPREEQYNSTYRVVS VL TVLHQDWLNGKEYKCKV SNKALPAPIEKTISKKQP REPQ VYTLPPSREEMTKNQ VSLYPSREEMTKNQ VSLVVEGF SNGQPENNYKTTPPPVLDSD GSFFL YSKL TVDKSRWQQG NVFSCSVMHEALHAHYTQK SLSLSPGKGGGSGGGGS GGGGSEVQLLESGGGLVQ PGGSLRLSCAASGFDFSRY WMTWVRQAPGKCLEWVS EINPDSRTINYTPLQDSLQNLQN DTAVYYCARPDHDYNPYYF NYWGQGTTVTVSS GGGGS GGGGSGGGGSGGGGSDIV AGACAGGCACCAGGACAA GGGCTTGAGTGGATGGGT CGAGTGTCTCCCAACAATG GAGCCACCAATACCAACCA GAAGTTCAAGGATCGTGTCGTCGACTCA 1AGATCCAG1 CCACTGCCTATAT GGAACTGCGCTCCTTGAG GAGTGAGGACACAGCAGT GTACTATTGCGCTAGGAGT ACCATGATAACGTCCTATT ACTTCGACTATTGGGGCCA AGGTACTCTGGTGACAGT GTCTAGC GCGTCGACAAA GGGCCCCTCCGTGH ICC TCTGCCAGCCAGCTGACTGAGGA GCCGCTCTGGGATGTCTG GTGAAGGATTACTTCCCTG AGCCA G TGA CCG TGAGCTGGAACTCTGGCGCCCTGA CCTCCGGA G TGCA TA CA TT TCCCGCTGTGCTGCAGTC CAGCGGCCTGTATAGCCT G TC TTCCG TGGTGA CCGT GCCTAGCTCTTCCCTGGG CACCCA GA CA TA CA TC TGC AACG TGAA TCA CAAGCCCT CCAA GAGT CAGAG GA GGAG GA TAA GA G CTGTGA TAAGACCCA TACA TGCCCA CCA TG TCCAGCTC CTGAGTTCCTGGGAGGAC CTTGCGTGTTCCTGH TCC TCCAAAGCCAAAGGA CA C CCTGA TGA TCTCTCGCACC CCTGAGGTGA CA TGCG TG L TQSPASLA VSLGQRA RPSQQSQYNSQY KPGQPPKLLIKYASNLESG VPARFSGSGSGTDFTL TISP VEAEDTA TYYCQQSWEIPL TFGCGTKLEIK (SEQ ID NO: 100) Petition 870250084408, of 19 / 09 / 2025, p. 66 / 297 55 / 214 Ab Amino Acid Sequence Nucleotide Sequence G TGGTGGA CG TG TCCCA C GAGGA TCCA GAGGTGAA G TTCAACTGGTA CG TGGA TG GCG TGGAGGTGCA TAA TG CTAAGACCAAGCCTAGGG AGGAGCAGTA CAA CAGCA CGTGGTCTCGGT GCTGACAGTGCTGCACCA GGACTGGCTGAACGGCAA GGAGTA CAA G TGCAAGGT GAGCAATAAGGCCCTGCC AGCTCCCATCGA GAA GA C CATCTCTAAGGCCAAGGG CCAGCCCA GA GAGCCTCA GGTGTATACACTGCCCCCT AGCCGCGAGGAGACCAGGACCAGGTGAGGTGCTGACTGCTGA TCTACCCA TCTGACA TCGC TG TGGA GTGGGAG TCCAA TGGCCAGCCCGAGAACAA TTA TAA GACCACACCACCC GTGCTGGACTCCGATGGC AGCTTCI1ICTGTACTCCA AGCTGA CCG TGGA TAA GA GCAGGTGGCAGCAGGGCA ACGTCACCAGGCCGAGGCCGA CGCTCA TTA TA CA CA GAAA TCTCTGTCCCTGAGCCCAG GCAAGGGTGGAGGGGGAT CcGGCGGCGGCGGCAGTG GCGGAGGAGGCTCCGAG GTGCAGCTGCTGGAATCT GGCGGAGGATTGGTTCAG CCTGGCGGCTCTCTGAGA CTGTCTTGGCCTGG Petition 870250084408, of 19 / 09 / 2025, p. 67 / 297 56 / 214 Ab Amino Acid Sequence Nucleotide Sequence GCTTCGACTTCTCCCGGTA TTGGATGACCTGGGTCCG ACAGGCTCCTGGCAAGTG TCTGGAATGGGTGTCCGA GATCAACCCCGACAGCCG GACCATCAACTACACCCC TAGCCTGAAGGACCATGCCAGCCAGTT CGCCAAGAACACCCTGTA CCTGCAGATGAACTCCCT GAGAGCCGAGGACACCG CCGTGTACTACTGTGCCA GACCTGACCACGACTACA ACCCCTACTACTTCAACTA CTGGGGCCAGGGCACCAC CGTGACAGTTTCTAGC GG CGGAGGTGGAAGCGGAGTAGGGGGGGGGGG CGGATCTGGTGGCGGTGG ATCTGA TA TCGTGCTGACC CAGTCTCCTGCCA GCCTG GCTGTTTCTCTGGGA CA GA GA GCCA CCA TCA GCTGC CGGCCTTCTCAGTCCGTG TCCACCTCCTCCAACTCCT A CA TCCACTGGTA TCA TCA AGAAGAG CCGAA GCCTTGA CG CCTCCAACCTGGAATCCG GCG TGCCA GCCA GA TTTT CCGGCTCTGGCTCTGGCA CCGACTTCA CCCTGA CAA TCTCTCCCGTGGAAGCTG AGGATACCGCCACCTACT ACTGCCAGCAGTCCTGGG AGA TCCCTCTGACCTTTGG CTAGGTGCTGCA CCGGA Petition 870250084408, of 19 / 09 / 2025, p. 68 / 297 57 / 214 Ab Amino Acid Sequence Nucleotide Sequence AATCAAA (SEQ ID NO: 142) LC-1 Natural Size Light Chain DIVMTQSPSFLSVGDRVT ITCKASQSVSTDVAWYQQK PGQAPKLLIYFASDRYTGVP DRFSGFTDFTGFTFFTFSQQYSSQTYSSQ GGGTKLEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEV THQGLSSPVTKSFNRGEC (SEQ ID NO: 101) GACATCGTGAT CAGTCAGT 1 CT CC 1GAGT GAGTGTTGGGGATAGAGT CACCATCACATGCAAAGCC AGCCAATCAGTCAGCACC GATGTAGCCTGGTATCAGC AGAAACCAGGCCAAGCTC CCAAGCTGCTGATCTACTT CGCAAGCGACAGGTACAC TGGTGTGCCAGATCGG11 1 TCTGGGTCTGGGATACCTACCTTGTCGACTGATTCGATCGATCG CTCCAGTCTGCAGGCTGA AGATGTTGCCGTCTACTAC TGTCAGCAGGACTATTCCT CTCCTCCTACC 1 1 1 GGAGG AGGCACTAAGCTGGAGAT AAAGCGTACGGTGGCCGC TCCATCCGTGTTCATC 1 1 1 CCACCCTCCGACGAGCAG CTGACCAGGGACCGGCTGGCTGCT AACAACTTCTACCCAAGAG AGGCCAAGGTGCAGTGGA AGGTGGATAACGCTCTGC AGAGCGGCAATTCTCAGG AGTCCGTGACCGAGCAGG ACAGCAAGGATTC TACATATTCCCTGAGCTCT ACCCTGACACTGTCCAAG GCCGATTACGAGAAGCCAC AAGGTGATTGTGGCTTGGTGACCCATCAGGGCCTG TCCAGCCCCGTGACAAAG AGCTTCAACCGCGGCGAG Petition 870250084408, dated 09 / 19 / 2025, p. 69 / 297 58 / 214 Ab Amino Acid Sequence Nucleotide Sequence TGT (SEQ ID NO: 143)

[00117] Tables 6 and 7 provide nucleotide sequences encoding exemplary CDRs for use in the 5T4 antigen-binding domains of the present invention. Table 6. Heavy Chain CDR Nucleotide Sequences Anti-5T4 Specimens CDRH1 CDRH2 CDRH3 A GGCTACAGCTTCA CAGACTACTACAT GCACT (SEQ ID NO: 84) CGAGTGTCTCCC AACAATGGAGCC ACCAATACCAACC AGAAGTTCAAGGA T (SEQ ID NO: 85) AGTACCATGATAA CGTCCTATTACTT CGACTATT (SEQ ID NO: 86) B GGCTTCGACTTCT CCCGGTATTGGAT GACC (SEQ ID NO: 87) GAGATCAACCCC GACAGCCGGACC ATCAACTACACCC CTAGCCTGAAGG AC (SEQ ID NO: 88) TGACCACGACTAC AACCCCTACTACT TCAACTAC(SEQ ID NO: 89) Table 7. Nucleotide Sequences of Light Chain CDRs Anti-5T4 specimens CDRH1 CDRH2 CDRH3 C GCCAGCCAATCA GTCAGCACCGAT GTAGCC (SEQ ID NO: 90) GCAAGCGACAGG TACACT (SEQ ID NO: 91) CAGCAGGACTATT CCTCTCCTCCTAC C (SEQ ID NO: 92) D CGGCCTTCTCAGT CCGTGTCCACCT CCTCCAACTCCTA CATCCAC (SEQ ID NO: 93) TACGCCTCCAACC TGGAATCC (SEQ ID NO: 94) CAGCAGTCCTGG GAGATCCCTCTGA CC (SEQ ID NO: 95)

[00118] Table 8 provides additional humanized variable heavy and light chain amino acid sequences for the 5T4 antigen-binding domains of the present invention. In Table 8, the sequences are shown. Petition 870250084408, dated 09 / 19 / 2025, p. 70 / 297 59 / 214 CDR sequences are in bold. Table 8. Humanized Anti-5T4 Variable Heavy and Light Chain Amino Acid Sequences No. Domain Amino Acid Sequence SEQ ID NO 2 5T4-VH EVQLLESGGGLVQPGGSLRLSCAASGF DFSRYWMTWVRQAPGKGLEWVSEINPD SRTINYTPSLKDRFTISRDNAKNTLYLQM NSLRAEDTAVYYCARPDHDYNPYYFNY WGQGTTVTVSS 102 5T4-VL DIVLTQSPASLAVSLGQRATISCRPSQSV STSSNSYIHWYQQKPGQPPKLLIKYASN LESGVPARFSGSGSGTDFTLTISPVEAE DTATYYCQQSWEIPLTFGGGTKLEIK 103 3 5T4-VH EVQLLESGGGLVQPGGSLRLSCAASGF DFSRYWMTWVRQAPGKGLEWVSEINPD SNTINYTPSLKDRFTISRDNAKNTLYLQM NSLRAEDTAVYYCASPDYDYNPYYFAY WGQGTLVTVSS 104 5T4-VL DIVLTQSPASLAVSLGQRATISCRASQSV STSRYSYMHWYQQKPGQPPKLLIKYAS NLESGVPARFSGSGSGTDFTLTISSLQA 105 DIVLTQSPASLAVSLGQRATISCRASQSV SSSSYNYMHWYQQKPGQPPKLLIYSAS TLESGVPARFSGSGSGTDFTLTISSLQAE DFATYYCQHSWEIPYTFGQGTKLEIK 107 Petition 870250084408, dated 09 / 19 / 2025, page 71 / 297 60 / 214 No. Control system SEQ ID NO 5 5T4-VH EVQLVQSGAEVKKPGASVKVSCKASGF NIKDTYMHWVRQAPGQGLEWMGRIDPA DGNTKFDPKFQGRVTITADTSSTSTAYME LSSLRSEDTAVYYCARFRRYDYVMDYW GQGTTVTVSS 108 5T4-VL DIVLTQSPASLAVSLGQRATITCRASESV DSYGNIFMHWYQQKPGQPPKLLIYLASN LESGVPARFSGSGSGTDFTLTISSLEAED FATYYCQQNNEDPWTFGGGTKLEIK 109 1 5T4-VH QVQLVQSGAEVKKPGASVKVSKASGY SFTDYYMHWVRQAPGQGLEWMGRVSP NNGATNTNQKFKDRVTMTRDTSISTAY MELRSLRSEDTAVYYCARSTMITSYYFD YWGQGTLVTVSS 96 5T4-VL DIVMTQSPSFLSVSVGDRVTITCKASQS VSTDVAWYQQKPGQAPKLLIYFASDRYT GVPDRFSGSGSGTDFTFTISSLQAEDVA 112 5T4 DIVMTQSPSSLSASVGDRVTITCKASQD VSIDVGWYQQKPGQAPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDFA TYYCQQHHIVPPTFGQGTKVEIK 113 7 5T4-VH EVQLVQSGAEVKKPGASVKVSCKASGY SFTGYYLHWVRQAPGQCLEWMGRVNP NNGGTIYNQNFKGRVTMTRDKSISTAYM ELRSLRSEDTAVYYCARSIMITTFDFDYW GQGTLVTVSS 114 Petition 870250084408, dated 09 / 19 / 2025, p. 72 / 297 61 / 214 No. Amino Sequence SEQ ID NO 5T4-VL DIVMTQSPSSLSASVGDRVTITCKASQD VNTAVVWYQQKPGQAPELLIYWASTRH TGVPDRFSGSGSGTDYTLTISSLQAEDF ATYYCQQHYSTPPTFGQGTKVEIK 115 8 5T4-VH QVQLVQSGAEVKKPGASVKISCKASGYT FSSYWIEWVRQAPGQGLEWMGEILPGS GRTNYNEKFKGRVTITADTSTSTAYMEL SSLRSEDTAVYYCARGNYGSSPYYFDY WGQGTLVTVSS 116 5T4-VL DIVLTQSPASLAVSLGQRATISCRASQSV STSRNSYMHWYQQKPGQPPKLLIKYAS GSTYYNEKFKGRVTMTADKSISTAYMEL SSLRSEDTAVYYCARGGRYGFDYWGQ GTTVTVSS 118 5T4-VL EIVLTQSPATLSASPGERVTLTTCTASSSV SSSYLHWYQQKPGLAPKLLIYSTSNLAS GVPARFSGSGSGTDYTLTISSLEPEDFAT YYCHQYHRSPLTFGGGTKLEIK 119 10 5T4-VH QVTLKESGPTLVKPTQTLTLTCTFSGFSL STSGVGVDWIRQPPGKALEWLAHIWWD DVKRYNPALKSRLTISKDTSKNQVVLTM TNMDPVDTATYYCARIADGYSAPWFAY WGQGTLVTVSS 120 5T4-VL DIQMTQSPSSSLSASVGDRVTITCKASQDI NKYIAWYQQKPGKAPKLLIYYTSTLQPGI PSRFSGSGSGTDFTFTISSLQPEDIATYY CLQCDNLWTFGGGTKLEIK 121

[00119] A person generally skilled in the art will understand that a 5T4 antigen-binding domain can comprise any combination of variable heavy and light domains described in Petition 870250084408, dated 09 / 19 / 2025, page 73 / 297 62 / 214 Table 8 or 9. Alternatively, the 5T4 antigen-binding domains may comprise the specific pair of variable heavy and light domains identified by the number in the left-hand column of Table 8 or 9.

[00120] Table 9 provides additional mouse variable heavy and light chain amino acid sequences for the 5T4 antigen-binding domains of the invention. Those commonly skilled in the art will understand that the mouse variable heavy and light domains can be humanized. Table 9. Heavy and Light Chain Amino Acid Sequences Anti-5T4 Mouse Variable Ab Domain Amino Acid Sequence SEQ ID NO 11 5T4_VH DVQLVESGGGLVQPGGSRKLSCAASGF TFSNFGMHWVRQAPEKGLEWVAYISSG TSTIYYADTVKGRFTISRDNPKNTLFLQM TSLRSEDTAMYYCARSRAYYRYEIDHW GQGTTLTVSS 122 5T4_VL DIVLTQSPASLAVSLGQRATISCRASQSV STSSSNSYVHWYQQKLGQPPKLLIKNAS NLESGVPARFSGSGSGTDFILNIHPVEEE DTATYYCQHSWEIPYTFGGGTKLEIK 123 12 5T4_VH DVQLVESGGGLAQPGGSRKLSCEASGF TFSSFGMHWVRQPPEKGLEWVAYISSG GSNIYYADTVKGRFTISRDNPKNTLSLQM TSLRSEDTAMYYCARWGDSYRYFDVW GAGTTVTVSS 124 5T4_VL QIVLTQSPAILSASPGEKVSITCSASSSVS FMHWFQQKPGTSPKLWIYSTSNLASGV PARFSGSGSGTSYSLTISRMEAEDAATY YCQQRSGYPPKFTFGSGTKLEIK 125 Petition 870250084408, dated 09 / 19 / 2025, page 74 / 297 63 / 214 From Domínio Sequência de Aminoácidos SEQ ID NO 13 5T4_VH EVKLLESGGGLVQPGGSLKLSCAASGFD FSRYWMTWVRQAPGKGLEWIGEINPDS RTINYTPPLKDKIIISRDNAKNTLYLQMNK VRSEDTALYYCARPDHEYNPYYFNNWG QGTTLTVSS 126 5T4_VL DIVLTQSPASLPVSLGQRATISCRPSQSV STSSNSYIHWYQQKPGQPPKLLIKYASN LEPGVPARFSGSGSGTDFTLNIHPVEEE DTATYYCQQSWEIPLTFGAGTKLLELK 127 2, 14 5T4_VH EVKLLESGGGLVQPGGSLKLSCAASGFD FSRYWMTWVRQAPGKGLEWIGEINPDS RTINYTPSLKDKFIISRDNAKNTLYLHMSK VRSEDTALYYCARPDHDYNPYYFNYWG QGTTLTVSS 128 5T4_VL DIVLTQSPASLAVSLGQRATISCRPSQSV STSSNSYIHWYQQKPGQPPKLLIKYASN LESGVPARFSGSGSGTDFTLNIHPVEEE DTATYYCQQSWEIPLTFGAGTKLELK 129 15 5T4_VH EVKLLESGGGLVQPGGSLKLSCAASGFD FSRYWMTWVRQAPGKGLEWIGEINPDS RTINYTPSLKDKFIISRDNAKNTLYLHMSK VRSEDTALYYCARPDHDYNPYYFNYWG QGTTLTVSS 128 5T4_VL DIVVTQSPASLAVSLGQRATISCRASQSV STSRYSYIHWYQQKPGQSPKLLIKYASN LESGVPPRFSGSGSGTDFTLNIHPVEEE DTATYYCQHSWEIPLTFGAGTKLELK 131 16 5T4_VH EVQLQQSGAELVKPGASVKLSCTASGFN IKDTYMHWVKQRPEQGLEWIGRIDPANG NTKYDPKFQGKATITSDTSSNTAYLQLSS LTSEDTAVYYCARFRRYALVMDYWGQG TSVTVSS 132 Petition 870250084408, dated 09 / 19 / 2025, p. 75 / 297 64 / 214 Ab Domínio Sequência de Aminoácidos SEQ ID NO 5T4_VL_ NIVLTQSPASLAVSLGQRATISCRASETID SYGNTFMHWYHQKPGQPPKLLIYLASNL ESGVPARFSGSGSRTDFTLTIDPVEADD AATYYCQQNNEDPWTFGGGTKLEIK 133 17 5T4_VH_ EVQLQQSGPDLVKPGASVRISCKASGYS FTGYYLHWVKQSHGESLEWIGRVNPNN GGTSYNQKFKGKAILTVDTSSNTVYMEL RSLTSEDSAVYNCARSTMITSYYFDYWG QGTTLTVSS 134 5T4_VL_ SIVMTQTPKFLLVSSGDRVTMTCKASQS VSNDVAWYQQKPGQSPKLLIYYVSNRYI GVPDRFTGSGYGTDFTFTISTVQAEDLA VYFCQQDYSSPPTFGGGTKLEIK 135 18 5T4_VH_ EVQLQQSGPDLVKPGASVRISCKASGYS FTGYYIHWVKQSHGKSLEWIGRVNPNN GGTIYNQKFKGKAILTVDKSSNTASMEY RSLTSEDSAVYYCARSTMITSYYFDYWG QGTTLTVSS 136 5T4_VL_ NIVMTQTPKFLLVSAGDRVTITCKASQSV NYDVAWYQQKPGQSPKPLIYYASKRYT GVPDRFTGSGFGTDFTFTINTVQAGDLAI YFCQQDYSSPPTFGGGTKLEIK 137 19 5T4_VH_ QVQLQQSGAELMKPGASVRISCKATGYT FSTYWIEWVRQRPGHGLEWIGEILPGSG RNNYNEKFKGKATFTADTSSNTAYIQLS SLTSEDSAVYYCAKGNYGSSPYYFDYW GQGTTLTVSS 138 5T4_VL_ DIVLTQSPASLVVSLGQRATISCRASQSV STSRNSYMHWYQQKPGQPPKVLIKYAS NLESGVPARFSGSGSGTDFTLNIHPVEE EDTATYYCQHSWEIPLTFGAGTKLELK 139 Petition 870250084408, dated 09 / 19 / 2025, p. 76 / 297 65 / 214 Ab Domínio Sequência of Aminoácidos SEQ ID NO 20 5T4_VH_ QVTLKESGPGILQPSQTLSLTCSFSGFSL STSGMGVGWIRQPSGKGLEWLAHIWW DDVKRYNPALKSRLTISKDTSSSQVFLNI ASVDTADTATYYCARIADGYYAPWFAYW GQGTLVTVSA 140 5T4_VL_ DIQMTQSPSSLSASLGGKVTITCKASQDI NKYIAWYQHKPGKGPRLIIHYTSTLQPDI PSRFSGSGSGRDYSFSISNLEPEDIATYF CLQCDDLWTFGGGTKIEIK 141 3 5T4-VH EVKLLESGGGLVQPGGSLKLSCAASGFD FSRYWMTWVRQAPGKGLEWIGINPDS NTINYTPSLKDKFIISRDNAKNTLYLQLTK VRSEDTGLYYCASPDYDYNPYYFAYWG QGTPLTVSS 156 5T4_VL DIVVTQSPASLAVSLGQRATISCRASQSV STSRYSYMHWYQQKPGQSPKLLIKYAS NLESGVPPRFSGSGSGTDFTLNIHPVEE EDTATYYCQHSWEIPLTFGAGTKLELK 157 4 5T4-VH DVQLVESGGGLVQPGGSRTLSCAASGF TFSSFGLHWVRQSPEKGLEWVAYISVGS STIYYADPVKGRFTISRDNPKNTLFLQMT SLRSEDTAIYYCARSRTYYRSEIDSWGQ GTTLTVSS 158 5T4_VL DIVLTQSPASLTVSLGQRATISCRASQSV SSSSYNYMHWYRQKPGQPPKLLIKSAST LESGVPARFSGSGSGTDFTLNIHPVEEE DTATYYCQHSWEIPYTFGGGTKLEIK 159 5 5T4-VH EVQLQQSGAELVKPGASVKLSCTASGFN IKDTYMHWVKQRPEQGLEWIGRIDPADG NTKFDPKFQGKATITADTSSNTAYLQLSS LTSEDTAVYYCARFRRYDYVMDYWGQG TSVTVSS 160 Petition 870250084408, dated 09 / 19 / 2025, p. 77 / 297 66 / 214 Ab Domínio Sequência of Aminoácidos SEQ ID NO 5T4_VL NIVLTQSPASLAVSLGQRATISCRASESV DSYGNIFMHWYQQIPGQPPKLLIYLASNL ESGVPARFSGSGSRTDFTLTIDPVEADD AATYYCQQNNEDPWTFGGGTKLEIK 161 1 5T4-VH EVQLQQSGPDLVKPGASVKISCKASGYS FTDYYMHWVKQSHGKSLEWIGRVSPNN GATNTNQKFKDKAILTVDKSSSTAYMDL RSLTSEDSAVYYCARSTMITSYYFDYWG QGTTLTVSS 162 5T4_VL SIVMTQTPKFLLVSAGDRITITCKASQSVS TDVAWYQQKPGQSPKLLIYFASDRYTGV PDRFTGSGNGTDFTFTITTVQAEDLAIYF CQQDYSSPPTFGGGTKLEIK 163 6 5T4-VH EVQLQQSGPDLVKPGASVRISCKASGYS FTGYYLHWVKQSHGKSLEWIGRVNPNN GATVYNQNFKGKAVLTVDKSSSTAYMEL RSLTSEDSAVYYCVRSIMITTYDFDYWG QGTTLTVSS 164 5T4_VL DIVMTQSHKFMSTSVGDRVSITCKASQD VSIDVGWYQQKPGQSPKLLIYWASTRHT GVPDRFTGSGSGTDYTLTISNVQAEDLA LYYCQQHHIVPPTFGSGTKLEIK 165 7 5T4-VH EVQLQQSGPDLVRPGASVKISCKASGYS FTGYYLHWVKQSHGKSLEWIGRVNPNN GGTIYNQNFKGKAMLNVDKSSTTAYMEL RSLTSEDSAVYYCARSIMITTFDFDYWG QGTTLTVSS 166 5T4_VL DIVMTQSHKFMSTSVGDRVSITCKASQD VNTAVVWYQQKPGQSPELLIYWASTRH TGVPDRFSGSGSGTDYTLTISSVQAEDL ALYYCQQHYSTPPTFGSGTKLEIK 167 Petition 870250084408, dated 09 / 19 / 2025, page 78 / 297 67 / 214 Ab Domain Amino Acid Sequence SEQ ID NO 8 5T4-VH QVQLQQSGAELMKPGASVKISCKATGYT FSSYWIEWVRQRPGHGLEWIGEILPGSG RTNYNEKFKGKATFTADTSSNTAYIQLSS LTSEDSAVYYCAKGNYGSSPYYFDYWG QGTTLTVSS 168 5T4_VL DIVLTQSPASLAVSLGQRATISCRASQSV STSRNSYMHWYQQKPGQPPKVLIKYAS NLESGVPARFSGSGSGTDFTLNIHPVEE EDTATYYCQHSWEIPLTFGAGTKLELK 169 9 5T4-VH QVQLQQSGPELVKPGASVKMSCKASGY TFTHYVISWVKQRTGQGLEWIGEIYPGS GSTYYNEKFKGKATLTADKSSNTAYMQL SSLTSEDSAVYFCARGGRYGFDYWGQG TTLTVSS 170 5T4_VL QIVLTQSPAIMSASLGERVTMTCTASSSV SSSYLHWYQQKPGSSPKLWIYSTSNLAS GVPARFSGSGSGTSYSLTISSMEAEDAV TYYCHQYHRSPLTFGAGTKLELK 171 10 5T4-VH QVTLKESGPGILQPSQTLSLTCSFSGFSL STSGVGVDWIRQPSGKGLEWLAHIWWD DVKRYNPALKSRLTISKDTSSSQVFLKIA SVDTADTATYYCARIADGYSAPWFAYW GQGTLVTVSA 172 5T4_VL DIQMTQSPSSLSASLGGKVTITCKASQDI NKYIAWYQHKPGKGPRLLIHYTSTLQPGI PSRFSGSGSGRDYSFSISNLEPEDIATYY CLQCDNLWTFGGGTKLEIK 173

[00121] The invention provides antigen-binding domains, antibody-binding domains, bispecific antibody-binding domains (e.g., bispecific T-cell antibodies), antibody-drug conjugates and chimeric receptors (CARs) comprising antigen-binding domains comprising variable heavy domains, paired with any of the variable light chain domains set out in Tables 8 and 9. Petition 870250084408, dated 09 / 19 / 2025, page 79 / 297 68 / 214 In some embodiments, the antibody or antibody-drug conjugate comprises a biparatopic antibody comprising a first antigen-binding domain that specifically binds to a first 5T4 epitope, a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope, wherein the first antigen-binding domain is operably linked to the second antigen-binding domain, and a chemotherapeutic agent. In some embodiments, the first and / or second antigen-binding domains comprise any of the variable heavy domains, paired with any of the variable light chain domains presented in Tables 8 and 9.

[00122] Antibody-drug conjugates that bind to at least one epitope of a 5T4 protein are provided here. In some embodiments, the antibody-drug conjugates bind to one epitope of a 5T4 antigen. In some embodiments, the antibody-drug conjugates bind to two epitopes of a 5T4 antigen.

[00123] In some embodiments, the antibody-drug conjugates comprise a first antigen-binding domain that specifically binds to a first 5T4 epitope; a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain. In some embodiments, the first and second antigen-binding domains are independently selected from a cluster consisting of a Fab fragment, an F(ab')2 fragment, an scFv, a scab, a dAb, a single-domain heavy chain antibody, a single-domain light chain antibody, and a full-size IgG antibody. In some embodiments, the first antigen-binding domain with Petition 870250084408, dated 09 / 19 / 2025, page 80 / 297 69 / 214 binds a full-size IgG antibody. In some embodiments, the full-size IgG antibody comprises two heavy chains and two light chains. In some embodiments of the antibody-drug conjugates described herein, the second antigen-binding domain comprises a scFv. In some embodiments, the antibody-drug conjugates comprise two second antigen-binding domain scFvs that bind specifically to the second 5T4 epitope.

[00124] In some embodiments, the scFv comprises a heavy chain and a light chain. In some embodiments, the C-terminal of the light chain is operably linked to the N-terminal of the heavy chain by means of a linker, or the C-terminal of the heavy chain is operably linked to the N-terminal of the light chain by means of a linker. In some embodiments, the linker connecting the heavy chain and the light chain comprises a sequence of SEQ ID NO: 153.

[00125] In some embodiments, the N-terminus of the second antigen-binding domain is operably linked to the C-terminus of a heavy chain of the first antigen-binding domain. In some embodiments, the C-terminus of the second antigen-binding domain is operably linked to the N-terminus of a heavy chain of the first antigen-binding domain. In some embodiments, the second antigen-binding domain is operably linked to the heavy chain of the first antigen-binding domain by means of a linker. In some embodiments, the linker comprises or consists of an amino acid sequence of SEQ ID NO: 152. Constant Antibody Region Domain

[00126] Antibodies, including monoclonal, bispecific and biparatopic antibodies comprising natural-sized IgG antibodies, are contemplated as being included within the scope of the present invention. In some embodiments, a natural-sized IgG antibody with Petition 870250084408, dated 09 / 19 / 2025, page 81 / 297 70 / 214 comprises two heavy chains and two light chains, each comprising a variable region domain and a constant region domain, as described in greater detail below. Those skilled in the art will understand that monoclonal antibodies, as well as bispecific and biparatopic antibodies comprising full-size IgG antibodies with the variable and constant domain arrangement described below, are contemplated as being included within the scope of the present invention.

[00127] In some embodiments, the constant region domain is an IgG1 isotype constant region domain. In some embodiments, the constant region domain comprises an amino acid sequence with SEQ ID NO: 148. In some embodiments, the antibody light chains comprise a variable region domain and a constant region domain. In some embodiments, the constant region domain is an IgG1 isotype constant region domain. In some embodiments, the light chain comprises an IgG1 isotype constant region domain, the constant region domain comprising an amino acid sequence of SEQ ID NO: 149.

[00128] In some embodiments, for example, those embodiments in which the antibody comprises an IgG1 constant region domain, the IgG1 constant region domain comprises at least one mutation that reduces effector function, extends half-life, or a combination thereof.

[00129] In some embodiments, at least one mutation comprises an F at position 237 with respect to SEQ ID NO: 100 (L234F), a C or A at position 242 with respect to SEQ ID NO: 100 (S239C / A), an A at position 437 with respect to SEQ ID NO: 100 (N434A), or a combination thereof. In some embodiments, the constant region domain comprises an F at position 237 with respect to Petition 870250084408, dated 09 / 19 / 2025, page 82 / 297 71 / 214 SEQ ID NO: 100 (L234F), a C or A at position 242 with respect to SEQ ID NO: 100 (S239C / A), and an A at position 437 with respect to SEQ ID NO: 100 (N434A). In some embodiments, at least one mutation comprises an F at position 237 with respect to SEQ ID NO: 100 (L234F). In some embodiments, at least one mutation comprises a C or A at position 242 with respect to SEQ ID NO: 100 (S239C / A). In some embodiments, at least one mutation comprises a C at position 242 with respect to SEQ ID NO: 100 (S239C / A). In some embodiments, at least one mutation comprises an A at position 242 with respect to SEQ ID NO: 100 (S239C / A). In some forms, at least one mutation comprises an A at position 437 with respect to SEQ ID NO: 100 (N434A).

[00130] In some embodiments, the antibody heavy chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 148, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it. In some embodiments, the antibody light chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 149, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it.In some embodiments, the antibody heavy chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 148, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith; and the first antibody light chain(s) comprise(s) a constant region domain comprising a... Petition 870250084408, dated 09 / 19 / 2025, p. 83 / 297 72 / 214 amino acid sequence of SEQ ID NO: 149, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00131] In some embodiments, the antibody heavy chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 148. In some embodiments, the antibody light chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 149. In some embodiments, the antibody heavy chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 148; and the first antibody light chain(s) comprise(s) a constant region domain comprising an amino acid sequence of SEQ ID NO: 149.

[00132] In some embodiments of the antibody-drug conjugate described herein, the antibody-drug conjugate comprises a full-size IgG antibody comprising a first antigen-binding domain and a second antigen-binding domain comprising a scFv. In some embodiments, the antibody-drug conjugate comprises four polypeptides. In some embodiments, the antibody-drug conjugate comprises two polypeptides comprising, from the N to the C termini, the IgG antibody heavy chain, a linker, and the second antigen-binding domain. In some embodiments, the antibody-drug conjugate comprises four polypeptides comprising (a) two polypeptides comprising, from the N to the C termini, the full-size IgG antibody heavy chain, a linker, and the second antigen-binding domain; and (b) two polypeptides comprising the full-size IgG antibody light chain. In some Petition 870250084408, dated 09 / 19 / 2025, p. 84 / 297 73 / 214 modes, the linker connecting the full-size IgG antibody heavy chain and the second antigen-binding domain comprises an amino acid sequence of SEQ ID NO: 152.U

[00133] In some embodiments of the antibody-drug conjugate described herein, the antibody-drug conjugate comprises a full-size IgG antibody comprising a first antigen-binding domain and a second antigen-binding domain comprising a scFv, and the antibody-drug conjugate comprises two polypeptides comprising, from the N to C termini, the second antigen-binding domain, a ligand, and the full-size IgG antibody heavy chain.In some embodiments, the first antigen-binding domain comprises a full-size IgG antibody and the second antigen-binding domain comprises an scFv, and the antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising, from the N to C termini, the second antigen-binding domain, a linker, and the first antigen-binding domain heavy chain; and (b) two polypeptides comprising the first antigen-binding domain light chain. In some embodiments, the linker connecting the second antigen-binding domain and the first antigen-binding domain heavy chain comprises an amino acid sequence of SEQ ID NO: 152. Heavy Chain CDRs

[00134] In some embodiments, the antigen-binding domains, as well as antibodies, antibody-drug conjugates and receptors comprising the same described herein, comprise a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4, and 13 to 23 or a sequence having 1, 2 or 3 substitutions Petition 870250084408, dated 09 / 19 / 2025, p. 85 / 297 74 / 214 substitutions, insertions, or deletions in relation to it; a CDR2 sequence of HC selected from the group consisting of SEQ ID NOs: 2, 5, and 24 to 26 and 28 to 39 or a sequence having 1, 2, or 3 substitutions, insertions, or deletions in relation to it; and a CDR3 sequence of HC selected from the group consisting of SEQ ID NOs: 3, 6, and 40 to 52 or a sequence having 1, 2, or 3 substitutions, insertions, or deletions in relation to it.

[00135] In some embodiments, the antigen-binding domains described herein comprise a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4 and 13 to 23; a HC CDR2 sequence selected from the group consisting of SEQ ID NOs: 2, 5, 24 to 26 and 28 to 39; and a HC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 3.

[00136] In some embodiments, the antigen-binding domains described herein comprise a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4, and 13 to 23; a HC CDR2 sequence selected from the group consisting of SEQ ID NOs: 2, 5, 24 to 26, and 28 to 39; and a HC CDR3 sequence comprising an amino acid sequence of SEQ ID NOs: 3, 6, and 40 to 52.

[00137] In some embodiments, the antibodies and antibody-drug conjugates described herein comprise a first and at least second antigen-binding domain, wherein the first and / or second antigen-binding domain comprises a heavy chain comprising a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4 and 13 to 23 or a Petition 870250084408, dated 09 / 19 / 2025, page 86 / 297 75 / 214 sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it; a CDR2 sequence from HC selected from the group consisting of SEQ ID NOs: 2, 5, 24 to 26 and 28 to 39 or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it; and a CDR3 sequence from HC selected from the group consisting of SEQ ID NOs: 3, 6, and 40 to 52 or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it, wherein one or more of the CDR1, CDR2 and CDR3 sequences are not the same between the first and second antigen-binding domains.

[00138] In some embodiments, the antibodies and antibody-drug conjugates described herein comprise a first and at least second antigen-binding domain, wherein the first and / or second antigen-binding domain comprises a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4 and 13 to 23; an HC CDR2 sequence selected from the group consisting of SEQ ID NOs: 2, 5, 24 to 26 and 28 to 39; and an HC CDR3 sequence selected from the group consisting of SEQ ID NOs: 3, 6, and 40 to 52, wherein one or more of the CDR1, CDR2 and CDR3 sequences are not the same between the first and second antigen-binding domains.

[00139] In some embodiments, the antibodies and antibody-drug conjugates described herein comprise an antigen-binding domain comprising a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from any heavy chain CDR1 (CDRH1) sequence listed in Table 1; an HC CDR2 selected from any heavy chain CDR2 (CDRH2) sequence listed in Table 1; and an HC CDR3 selected from any heavy chain CDR3 (CDRH3) sequence listed in Table 1. Petition 870250084408, dated 09 / 19 / 2025, page 87 / 297 76 / 214

[00140] Those skilled in the art would understand that the antigen-binding domains, antibodies, antibody-drug conjugates, and receptors of the present invention may comprise a heavy chain comprising any CDRH1, CDRH2, or CDRH3 sequence listed in Table 1. In some embodiments, the heavy chain may comprise a combination of a CDRH1, a CDRH2, and a CDRH3 within a single row of Table 1. In some embodiments, the antibody-drug conjugates may comprise a heavy chain comprising a combination of a CDRH1, a CDRH2, and a CDRH3 wherein the CDRH1, CDRH2, and CDRH3 are not in the same row in Table 1. Those skilled in the art would understand that the antibody-drug conjugate of the present invention may comprise a heavy chain comprising any CDRH1 sequence listed in Table 1, in combination with any CDRH2 sequence listed in Table 1, in combination with any CDRH3 sequence. listed in Table 1.

[00141] In some embodiments, the variable region domain of heavy chain comprises: (a) a CDR1 of HC comprising SEQ ID NO: 1, a CDR2 of HC comprising SEQ ID NO: 2, and a CDR3 of HC comprising SEQ ID NO: 3; (b) a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 5, and a CDR3 of HC comprising SEQ ID NO: 6; (c) a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 24, and a CDR3 of HC comprising SEQ ID NO: 40; (d) a CDR1 of HC comprising SEQ ID NO: 13, a CDR2 of HC comprising SEQ ID NO: 25, and a CDR3 of HC comprising SEQ ID NO: 41; (e) a CDR1 of HC comprising SEQ ID NO: 14, a CDR2 of HC comprising SEQ ID NO: 26, and a CDR3 of HC comprising SEQ ID NO: 42; (f) a CDR1 of HC comprising SEQ ID NO: Petition 870250084408, dated 09 / 19 / 2025, p. 88 / 297 77 / 214 (g) a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 29, and a CDR3 of HC comprising SEQ ID NO: 44; (h) a CDR1 of HC comprising SEQ ID NO: 16, a CDR2 of HC comprising SEQ ID NO: 30, and a CDR3 of HC comprising SEQ ID NO: 45; (i) a CDR1 of HC comprising SEQ ID NO: 17, a CDR2 of HC comprising SEQ ID NO: 31, and a CDR3 of HC comprising SEQ ID NO: 46; (j) a CDR1 of HC comprising SEQ ID NO: 18, a CDR2 of HC comprising SEQ ID NO: 32, and a CDR3 of HC comprising SEQ ID NO: 47; (k) a CDR1 of HC comprising SEQ ID NO: 19, a CDR2 of HC comprising SEQ ID NO: 33, and a CDR3 of HC comprising SEQ ID NO: 48; (l) a CDR1 of HC comprising SEQ ID NO: 20, a CDR2 of HC comprising SEQ ID NO: 34, and a CDR3 of HC comprising SEQ ID NO: 49;(m) a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 35, and a CDR3 of HC comprising SEQ ID NO: 50; (n) a CDR1 of HC comprising SEQ ID NO: 14, a CDR2 of HC comprising SEQ ID NO: 36, and a CDR3 of HC comprising SEQ ID NO: 51; (o) a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 37, and a CDR3 of HC comprising SEQ ID NO: 3; (p) a CDR1 of HC comprising SEQ ID NO: 21, a CDR2 of HC comprising SEQ ID NO: 38, and a CDR3 of HC comprising SEQ ID NO: 3; (q) a CDR1 of HC comprising SEQ ID NO: 22, a CDR2 of HC comprising SEQ ID NO: 39, and a CDR3 of HC comprising SEQ ID NO: 45; or (r) a CDR1 of HC comprising SEQ ID NO: 23, a CDR2 of HC comprising SEQ ID NO: 32, and a CDR3 of HC comprising SEQ ID NO: 52.; Petition 870250084408, dated 09 / 19 / 2025, p. 89 / 297 78 / 214 Lightweight CDRs

[00142] In some embodiments, the antigen-binding domains, as well as antibodies, antibody-drug conjugates and receptors comprising the same described herein comprise a light chain (LC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 7, 10 and 53 to 66 or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; a light chain CDR2 sequence selected from the group consisting of SEQ ID NOs: 8, 11 and 67 to 75 or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; a light chain CDR3 sequence selected from the group consisting of SEQ ID NOs: 9, 12 and 76 to 83 or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto.

[00143] In some embodiments, the antibody-drug conjugates described herein comprise a first and a second antigen-binding domain, wherein the first and / or second antigen-binding domain comprises a light chain (LC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 7, 10, and 53 to 66 or a sequence having 1, 2, or 3 substitutions, insertions, or deletions thereto; a light chain CDR2 sequence selected from the group consisting of SEQ ID NOs: 8, 11, and 67 to 75 or a sequence having 1, 2, or 3 substitutions, insertions, or deletions thereto; a CDR3 sequence from LC selected from the group consisting of SEQ ID NOs: 9, 12, and 76 to 83 or a sequence having 1, 2, or 3 substitutions, insertions, or deletions relative to it, wherein one or more of the CDR1, CDR2, and CDR3 sequences are not the same between the first and second antigen-binding domains.

[00144] In some embodiments, antibody conjugates Petition 870250084408, dated 09 / 19 / 2025, p. 90 / 297 79 / 214 drugs described herein comprise a first and a second antigen-binding domain, wherein the first and / or second antigen-binding domain comprises a light chain (LC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 7, 10, and 53 to 66; a LC CDR2 sequence selected from the group consisting of SEQ ID NOs: 8, 11, and 67 to 75; a LC CDR3 sequence selected from the group consisting of SEQ ID NOs: 9, 12, and 76 to 83, wherein one or more of the CDR1, CDR2, and CDR3 sequences are not the same between the first and second antigen-binding domains.

[00145] In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising a CDR1 HC sequence comprising an amino acid sequence of SEQ ID NO: 1, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; a CDR2 HC sequence comprising an amino acid sequence of SEQ ID NO: 2, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; and a CDR3 HC sequence comprising an amino acid sequence of SEQ ID NO: 3, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto.

[00146] In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 7, or a sequence having 1, 2 or 3 substitutions, insertions or deletions relative to it; a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 8, or a sequence having 1, 2 or 3 substitutions, insertions or deletions relative to it; and a CDR3 sequence of LC comprising a sequence of Petition 870250084408, dated 09 / 19 / 2025, p. 91 / 297 80 / 214 amino acid of SEQ ID NO: 9, or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it.

[00147] In some embodiments, the first antigen-binding domain comprises a heavy chain variable region domain comprising an HC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 1; an HC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 2; and an HC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 3. In some embodiments, the first antigen-binding domain comprises a light chain variable region domain comprising an LC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 7; an LC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 8; and an LC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 9.

[00148] In some embodiments, the first antigen-binding domain comprises a heavy chain variable region domain comprising an HC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 1; an HC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 2; an HC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 3; and a light chain variable region domain comprising an LC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 7; an LC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 8; and an LC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 9.

[00149] In some embodiments of the antibody-drug conjugate, the first antigen-binding domain comprises a Petition 870250084408, dated 09 / 19 / 2025, p. 92 / 297 81 / 214 variable region heavy chain domain comprising a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1; a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 2; a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 3; and a variable region light chain domain comprising a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 10; a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 11; and a CDR3 sequence of LC comprising an amino acid sequence of SEQ ID NO: 12.

[00150] In some embodiments, the second antigen-binding domain comprises a heavy chain variable region domain comprising an HC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 4; an HC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 5; an HC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 6. In some embodiments, the second antigen-binding domain comprises a light chain variable region domain comprising an LC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 10; an LC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 11; and an LC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 12.

[00151] In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1; a CDR2 sequence of HC comprising an amino acid sequence of SEQ Petition 870250084408, dated 09 / 19 / 2025, page 93 / 297 82 / 214 ID NO: 2; and a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 3; and a light chain variable region domain comprising a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 7; a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 8; and a CDR3 sequence of LC comprising an amino acid sequence of SEQ ID NO: 9; and the second antigen-binding domain comprises a heavy chain variable region domain comprising a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 4; a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5; a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6; and the variable region light chain domain comprising a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 10;a CDR2 sequence of LC comprising an amino acid sequence with SEQ ID NO: 11; and a CDR3 sequence of LC comprising an amino acid sequence with SEQ ID NO: 12.

[00152] In some embodiments, the first antigen-binding domain comprises a heavy chain variable region domain comprising an HC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 1; an HC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 2; and an HC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 3; and a light chain variable region domain comprising an LC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 10; an LC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 11; and an LC CDR3 sequence that Petition 870250084408, dated 09 / 19 / 2025, p. 94 / 297 83 / 214 comprises an amino acid sequence with SEQ ID NO: 12; and the second antigen-binding domain comprises a heavy chain variable region domain comprising an HC CDR1 sequence comprising an amino acid sequence with SEQ ID NO: 4; an HC CDR2 sequence comprising an amino acid sequence with SEQ ID NO: 5; an HC CDR3 sequence comprising an amino acid sequence with SEQ ID NO: 6; and a light chain variable region domain comprising an LC CDR1 sequence comprising an amino acid sequence with SEQ ID NO: 7; an LC CDR2 sequence comprising an amino acid sequence with SEQ ID NO: 8; and an LC CDR3 sequence comprising an amino acid sequence with SEQ ID NO: 9.

[00153] Those skilled in the art would understand that the antigen-binding domains, antibodies, antibody-drug conjugates, and receptors comprising the same of the present invention may comprise a light chain comprising any sequence of CDRL1, CDRL2, or CDRL3 listed in Table 2. In some embodiments, the light chain may comprise a combination of a CDRL1, a CDRL2, and a CDRL3 within a single row of Table 2. In some embodiments, the antigen-binding domains comprise a light chain comprising a combination of a CDRL1, a CDRL2, and a CDRL3 wherein the CDRL1, CDRL2, and CDRL3 are not in the same row in Table 2.Those skilled in the art would understand that the antigen-binding domains of the present invention may comprise a light chain comprising any CDRL1 sequence listed in Table 2, in combination with any CDRL2 sequence listed in Table 2, in combination with any CDRL3 sequence listed in Table 2. Petition 870250084408, dated 09 / 19 / 2025, page 95 / 297 84 / 214

[00154] In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising: (a) an LC CDR1 comprising SEQ ID NO: 7, an LC CDR2 comprising SEQ ID NO: 8, and an LC CDR3 comprising SEQ ID NO: 9; (b) an LC CDR1 comprising SEQ ID NO: 10, an LC CDR2 comprising SEQ ID NO: 11, and an LC CDR3 comprising SEQ ID NO: 12; (c) an LC CDR1 comprising SEQ ID NO: 53, an LC CDR2 comprising SEQ ID NO: 11, and an LC CDR3 comprising SEQ ID NO: 76; (d) a CDR1 LC comprising SEQ ID NO: 54, a CDR2 LC comprising SEQ ID NO: 67, and a CDR3 LC comprising SEQ ID NO: 77; (e) a CDR1 LC comprising SEQ ID NO: 55, a CDR2 LC comprising SEQ ID NO: 68, and a CDR3 LC comprising SEQ ID NO: 78; (f) a CDR1 LC comprising SEQ ID NO: 56, a CDR2 LC comprising SEQ ID NO: 69, and a CDR3 LC comprising SEQ ID NO: 79;(g) a CDR1 LC comprising SEQ ID NO: 57, a CDR2 LC comprising SEQ ID NO: 69, and a CDR3 LC comprising SEQ ID NO: 79; (h) a CDR1 LC comprising SEQ ID NO: 58, a CDR2 LC comprising SEQ ID NO: 11, and a CDR3 LC comprising SEQ ID NO: 76; (i) a CDR1 LC comprising SEQ ID NO: 59, a CDR2 LC comprising SEQ ID NO: 70, and a CDR3 LC comprising SEQ ID NO: 80; (j) a CDR1 LC comprising SEQ ID NO: 60, a CDR2 LC comprising SEQ ID NO: 71, and a CDR3 LC comprising SEQ ID NO: 81; (k) a CDR1 LC comprising SEQ ID NO: 61, a CDR2 LC comprising SEQ ID NO: 72, and a CDR3 LC comprising SEQ ID NO: 77; (l) a CDR1 LC comprising SEQ ID NO: 62, a CDR2 LC comprising SEQ ID NO: 70, and a CDR3 LC comprising; Petition 870250084408, dated 09 / 19 / 2025, pp. 96 / 297 85 / 214 of SEQ ID NO: 82; (m) a CDR1 of LC comprising SEQ ID NO: 10, a CDR2 of LC comprising SEQ ID NO: 73, and a CDR3 of LC comprising SEQ ID NO: 12; (n) a CDR1 of LC comprising SEQ ID NO: 63, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; (o) a CDR1 of LC comprising SEQ ID NO: 64, a CDR2 of LC comprising SEQ ID NO: 68, and a CDR3 of LC comprising SEQ ID NO: 78; (p) a CDR1 LC comprising SEQ ID NO: 65, a CDR2 LC comprising SEQ ID NO: 74, and a CDR3 LC comprising SEQ ID NO: 9; (q) a CDR1 LC comprising SEQ ID NO: 66, a CDR2 LC comprising SEQ ID NO: 75, and a CDR3 LC comprising SEQ ID NO: 9; ® a CDR1 LC comprising SEQ ID NO: 58, a CDR2 LC comprising SEQ ID NO: 11, and a CDR3 LC comprising SEQ ID NO: 76;or (s) a CDR1 LC comprising SEQ ID NO: 60, a CDR2 LC comprising SEQ ID NO: 71, and a CDR3 LC comprising SEQ ID NO: 83.;

[00155] In some embodiments, the variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 1, a CDR2 of HC comprising SEQ ID NO: 2, and a CDR3 of HC comprising SEQ ID NO: 3, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 7, a CDR2 of LC comprising SEQ ID NO: 8, and a CDR3 of LC comprising SEQ ID NO: 9.

[00156] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 4, a HC CDR2 comprising SEQ ID NO: 5, and a HC CDR3 comprising SEQ ID NO: 6, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 10, a LC CDR2 comprising SEQ ID NO: Petition 870250084408, dated 09 / 19 / 2025, page 97 / 297 86 / 214 11, and a CDR3 of LC comprising SEQ ID NO: 12.

[00157] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 4, a HC CDR2 comprising SEQ ID NO: 24, and a HC CDR3 comprising SEQ ID NO: 40, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 53, a LC CDR2 comprising SEQ ID NO: 11, and a LC CDR3 comprising SEQ ID NO: 76.

[00158] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 13, a HC CDR2 comprising SEQ ID NO: 25, and a HC CDR3 comprising SEQ ID NO: 41, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 54, a LC CDR2 comprising SEQ ID NO: 67, and a LC CDR3 comprising SEQ ID NO: 77.

[00159] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 14, a HC CDR2 comprising SEQ ID NO: 26, and a HC CDR3 comprising SEQ ID NO: 42, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 55, a LC CDR2 comprising SEQ ID NO: 68, and a LC CDR3 comprising SEQ ID NO: 78.

[00160] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 15, a HC CDR2 comprising SEQ ID NO: 28, and a HC CDR3 comprising SEQ ID NO: 43, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 56, a LC CDR2 comprising SEQ ID NO: 69, and a LC CDR3 comprising SEQ ID NO: 79.

[00161] In some forms, the variable region domain of Petition 870250084408, dated 09 / 19 / 2025, pp. 98 / 297 87 / 214 heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 29, and a CDR3 of HC comprising SEQ ID NO: 44, and the variable region domain of light chain comprises a CDR1 of LC comprising SEQ ID NO: 57, a CDR2 of LC comprising SEQ ID NO: 69, and a CDR3 of LC comprising SEQ ID NO: 79.

[00162] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 16, a HC CDR2 comprising SEQ ID NO: 30, and a HC CDR3 comprising SEQ ID NO: 45, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 58, a LC CDR2 comprising SEQ ID NO: 11, and a LC CDR3 comprising SEQ ID NO: 76.

[00163] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 17, a HC CDR2 comprising SEQ ID NO: 31, and a HC CDR3 comprising SEQ ID NO: 46, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 59, a LC CDR2 comprising SEQ ID NO: 70, and a LC CDR3 comprising SEQ ID NO: 80.

[00164] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 18, a HC CDR2 comprising SEQ ID NO: 32, and a HC CDR3 comprising SEQ ID NO: 47, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 60, a LC CDR2 comprising SEQ ID NO: 71, and a LC CDR3 comprising SEQ ID NO: 81.

[00165] In some embodiments, the variable region domain of heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 19, a CDR2 of HC comprising SEQ ID NO: 33, and a Petition 870250084408, dated 09 / 19 / 2025, page 99 / 297 88 / 214 CDR3 of HC comprising SEQ ID NO: 48, and the variable region domain of the light chain comprising a CDR1 of LC comprising SEQ ID NO: 61, a CDR2 of LC comprising SEQ ID NO: 72, and a CDR3 of LC comprising SEQ ID NO: 77.

[00166] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 20, a HC CDR2 comprising SEQ ID NO: 34, and a HC CDR3 comprising SEQ ID NO: 49, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 62, a LC CDR2 comprising SEQ ID NO: 70, and a LC CDR3 comprising SEQ ID NO: 82.

[00167] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 4, a HC CDR2 comprising SEQ ID NO: 35, and a HC CDR3 comprising SEQ ID NO: 50, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 10, a LC CDR2 comprising SEQ ID NO: 73, and a LC CDR3 comprising SEQ ID NO: 12.

[00168] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 4, a HC CDR2 comprising SEQ ID NO: 5, and a HC CDR3 comprising SEQ ID NO: 6, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 63, a LC CDR2 comprising SEQ ID NO: 11, and a LC CDR3 comprising SEQ ID NO: 76.

[00169] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 14, a HC CDR2 comprising SEQ ID NO: 36, and a HC CDR3 comprising SEQ ID NO: 51, and the light chain variable region domain comprises a LC CDR1 comprising Petition 870250084408, dated 09 / 19 / 2025, page 100 / 297 89 / 214 of SEQ ID NO: 64, a CDR2 of LC comprising SEQ ID NO: 68, and a CDR3 of LC comprising SEQ ID NO: 78.

[00170] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 15, a HC CDR2 comprising SEQ ID NO: 37, and a HC CDR3 comprising SEQ ID NO: 3, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 65, a LC CDR2 comprising SEQ ID NO: 74, and a LC CDR3 comprising SEQ ID NO: 9.

[00171] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 21, a HC CDR2 comprising SEQ ID NO: 38, and a HC CDR3 comprising SEQ ID NO: 3, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 66, a LC CDR2 comprising SEQ ID NO: 75, and a LC CDR3 comprising SEQ ID NO: 9.

[00172] In some embodiments, the variable heavy chain region domain comprises a HC CDR1 comprising SEQ ID NO: 22, a HC CDR2 comprising SEQ ID NO: 39, and a HC CDR3 comprising SEQ ID NO: 45, and a variable light chain region comprises a LC CDR1 comprising SEQ ID NO: 58, a LC CDR2 comprising SEQ ID NO: 11, and a LC CDR3 comprising SEQ ID NO: 76.

[00173] In some embodiments, the heavy chain variable region domain comprises a HC CDR1 comprising SEQ ID NO: 23, a HC CDR2 comprising SEQ ID NO: 32, and a HC CDR3 comprising SEQ ID NO: 52, and the light chain variable region domain comprises a LC CDR1 comprising SEQ ID NO: 60, a LC CDR2 comprising SEQ ID NO: 71, and a LC CDR3 comprising SEQ ID NO: 83. Petition 870250084408, dated 09 / 19 / 2025, page 101 / 297 90 / 214 Variable region domains of heavy chain

[00174] In some embodiments of the antigen-binding domains, as well as antibodies, antibody-drug conjugates and receptors comprising the same as those of the present invention, the antigen-binding domain comprises at least one variable region heavy chain domain comprising a sequence selected from the group consisting of SEQ ID NOs: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 169, 170, and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% agreement with the same.In some embodiments, the antigen-binding domain comprises a single variable region heavy chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 169, 170, and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00175] In some embodiments, the antibody or antibody-drug conjugate comprises at least two variable region heavy chain domains each comprising a sequence independently selected from the group consisting of SEQ ID NOs: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 169, 170 and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with the same. In some embodiments, the antibody or antibody-drug conjugate comprises two variable region heavy chain domains, each comprising a select sequence. Petition 870250084408, dated 09 / 19 / 2025, page 102 / 297 91 / 214 independently of the group consisting of SEQ ID NO: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 169, 170 and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it. In some embodiments, the two variable heavy chain region domains are not the same. In some embodiments, the antibody or antibody-drug conjugate comprises more than two variable region heavy chain domains comprising a sequence selected from the group consisting of SEQ ID NO: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 169, 170 and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00176] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00177] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00178] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 102, or Petition 870250084408, dated 09 / 19 / 2025, page 103 / 297 92 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00179] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 104, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00180] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 106, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00181] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 108, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00182] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 112, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00183] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 114, or Petition 870250084408, dated 09 / 19 / 2025, page 104 / 297 93 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00184] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 116, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00185] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 118, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00186] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 120, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00187] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 122, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00188] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 124, or Petition 870250084408, dated 09 / 19 / 2025, page 105 / 297 94 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00189] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 126, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00190] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 128, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00191] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 132, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00192] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 134, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00193] In some embodiments, the antibody-drug conjugate comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 136, Petition 870250084408, dated 09 / 19 / 2025, page 106 / 297 95 / 214 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00194] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 138, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00195] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 140, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00196] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 156, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00197] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 158, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00198] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 160, or Petition 870250084408, dated 09 / 19 / 2025, page 107 / 297 96 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00199] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 162, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00200] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 164, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00201] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 166, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00202] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 168, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00203] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 170, or Petition 870250084408, dated 09 / 19 / 2025, page 108 / 297 97 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00204] In some embodiments, the antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00205] In some embodiments, for example, those embodiments in which the antigen-binding domain is incorporated into a biparatopic antibody or antibody-drug conjugate, the first and / or second antigen-binding domains comprise a variable region heavy chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 56, 158, 160, 162, 164, 166, 169, 170 and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identification with the same.

[00206] In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. Petition 870250084408, dated 09 / 19 / 2025, page 109 / 297 98 / 214 less than 99% identity thereto. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 102 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 104 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 106 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 108 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 112 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 114. Petition 870250084408, dated 09 / 19 / 2025, page 110 / 297 99 / 214 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable heavy chain region domain comprising an amino acid sequence of SEQ ID NO: 116 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable heavy chain region domain comprising an amino acid sequence of SEQ ID NO: 118 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 120 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 122 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 124 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises one. Petition 870250084408, dated 09 / 19 / 2025, page 111 / 297 100 / 214 variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 126 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 128 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 132 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 134 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 136 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 138 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least. Petition 870250084408, dated 09 / 19 / 2025, p. 112 / 297 101 / 214 99% identity with the same. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 140 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with the same. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 156 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with the same.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 158 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 160 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 162 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 164 or a se. Petition 870250084408, dated 09 / 19 / 2025, page 113 / 297 102 / 214 sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 166 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 168 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 170 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 172 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00207] In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second Petition 870250084408, dated 09 / 19 / 2025, page 114 / 297 The antigen-binding domain 103 / 214 comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 97 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 102 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 104 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 106 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 108 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 112 or a sequence having at least 80%, at least 85%, at least 90% identity therewith. Petition 870250084408, dated 09 / 19 / 2025, page 115 / 297 104 / 214 at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 114 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 116 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 118 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 120 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 122 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising a sequence of... Petition 870250084408, dated 09 / 19 / 2025, page 116 / 297 105 / 214 amino acid of SEQ ID NO: 124 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 126 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 128 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 132 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 134 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 136 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some sports, the second Sunday. Petition 870250084408, dated 09 / 19 / 2025, p. 117 / 297 106 / 214 The antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 138 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 140 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 156 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 158 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 160 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 162 or a sequence having at least 80%, at least 85%, at least 90%, at least. Petition 870250084408, dated 09 / 19 / 2025, page 118 / 297 107 / 214 95%, at least 97%, or at least 99% identity thereto. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 164 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 166 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 168 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence with SEQ ID NO: 170 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 172 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. Light chain variable region domains

[00208] In some modalities of the linking domains to the anti-Petition 870250084408, of 19 / 09 / 2025, page 119 / 297 108 / 214 geno, as well as the antibodies, antibody-drug conjugates and receptors comprising the same of the present invention, the antibody-drug conjugate comprising a variable region light chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% agreement with the same.In some embodiments, the antibody or antibody-drug conjugate comprises at least one variable region light chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00209] In some embodiments, the antibody or antibody-drug conjugate comprises at least two variable region light chain domains each comprising an independently selected sequence from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% of identity with the same. In some embodiments, the antibody or antibody-drug conjugate comprises two variable light chain region domains each comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, Petition 870250084408, dated 09 / 19 / 2025, page 120 / 297 109 / 214 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it. In some embodiments, the two variable light chain region domains are not the same. In some embodiments of the antibodies or antibody-drug conjugates of the present invention, the antibody or antibody-drug conjugate comprises more than two variable region light chain domains comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identical.

[00210] In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00211] In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 99, or Petition 870250084408, dated 09 / 19 / 2025, page 121 / 297 110 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 103, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 105, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 107, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 109, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments of the antigen-binding domain of the present invention, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 113, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a region domain. Petition 870250084408, dated 09 / 19 / 2025, page 122 / 297 111 / 214 variable light chain comprising an amino acid sequence of SEQ ID NO: 115, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 117, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 119, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 121, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 123, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 125, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some modalities, the domain of. Petition 870250084408, dated 09 / 19 / 2025, p. 123 / 297 112 / 214 antigen binding comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 127, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the antigen binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 129, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 131, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 133, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 135, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 137, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity. Petition 870250084408, dated 09 / 19 / 2025, p. 124 / 297 113 / 214 with the same. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 139, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 141, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 157, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 159, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 161, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 163, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 95%. Petition 870250084408, dated 09 / 19 / 2025, page 125 / 297 114 / 214 with at least 97% or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 165, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 167, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 169, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 171, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00212] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 96, and the light chain variable region domain comprises Petition 870250084408, dated 09 / 19 / 2025, pp. 126 / 297 115 / 214 an amino acid sequence with SEQ ID NO: 98.

[00213] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 97, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 99.

[00214] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 102, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 103.

[00215] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 104, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 105.

[00216] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 106, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 107.

[00217] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 108, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 109.

[00218] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 112, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 113.

[00219] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 114, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 115.

[00220] In some forms, the variable region domain of Petition 870250084408, dated 09 / 19 / 2025, pp. 127 / 297 The 116 / 214 heavy chain comprises an amino acid sequence with SEQ ID NO: 116, and the variable region domain of the light chain comprises an amino acid sequence with SEQ ID NO: 117.

[00221] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 118, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 119.

[00222] In some embodiments, the heavy chain variable region domain comprises an amino acid sequence with SEQ ID NO: 120, and the light chain variable region domain comprises an amino acid sequence with SEQ ID NO: 121.

[00223] In some embodiments, for example, those embodiments in which the antigen-binding domain is incorporated into a biparatopic antibody or antibody-drug conjugate, the first and / or second antibodies comprise a variable region light chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identification with the same.

[00224] In some embodiments, the first and second antigen-binding domains comprise a variable region light chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00225] In some modalities, the first linking domain to Petition 870250084408, dated 09 / 19 / 2025, pp. 128 / 297 117 / 214 antigen comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 103, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 105, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 107, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 109, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least. Petition 870250084408, dated 09 / 19 / 2025, pp. 129 / 297 118 / 214 99% identity thereto. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 113, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 115, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 117, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 119, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 121, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 123, or a sequence having. Petition 870250084408, dated 09 / 19 / 2025, page 130 / 297 119 / 214 at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 125, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 127, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 129, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 131, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 133, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region domain of approximately... Petition 870250084408, dated 09 / 19 / 2025, page 131 / 297 120 / 214 light chain comprising an amino acid sequence of SEQ ID NO: 135, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 137, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 139, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 141, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 157, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 159, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some modalities. Petition 870250084408, dated 09 / 19 / 2025, p. 132 / 297 121 / 214 embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 161, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 163, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 165, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 167, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 169, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 171, or a sequence having at least 80%, at least 85%, at least 97%, or at least 99% identity therewith. Petition 870250084408, dated 09 / 19 / 2025, page 133 / 297 122 / 214 90%, at least 95%, at least 97%, or at least 99% identity thereto. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto.

[00226] In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 103, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 105, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain. Petition 870250084408, dated 09 / 19 / 2025, page 134 / 297 123 / 214 comprising an amino acid sequence of SEQ ID NO: 107, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 109, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 113, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 115, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 117, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 119, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some modalities, the. Petition 870250084408, dated 09 / 19 / 2025, p. 135 / 297 The second antigen-binding domain, 124 / 214, comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 121, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 123, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 125, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 127, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 129, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 131, or a sequence having at least 80%, at least 85%, at least 90%, at least. Petition 870250084408, dated 09 / 19 / 2025, page 136 / 297 125 / 214 in 95%, at least 97%, or at least 99% identity with the same. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 133, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with the same. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 135, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with the same.In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 137, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 139, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 141, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of... Petition 870250084408, dated 09 / 19 / 2025, page 137 / 297 126 / 214 SEQ ID NO: 157, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 159, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence of SEQ ID NO: 161, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 163, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable light chain region domain comprising an amino acid sequence with SEQ ID NO: 165, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 167, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some forms, the second antigen-binding domain comprises... Petition 870250084408, dated 09 / 19 / 2025, page 138 / 297 127 / 214 comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 169, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 171, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence with SEQ ID NO: 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00227] In some embodiments of the antibody-drug conjugate antibodies of the present invention, the first and / or second antigen-binding domains comprise a variable region heavy chain domain comprising a sequence selected from the group consisting of SEQ ID NO: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 168, 170 and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with the same; and a variable region domain of the light chain comprising a sequence selected from the group consisting of SEQ ID NO: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity. Petition 870250084408, dated 09 / 19 / 2025, page 139 / 297 128 / 214 of identity with the same.

[00228] In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96 or 97. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98 or 99. In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96 or 97, and a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98 or 99.

[00229] In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the first antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith; and a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or a sequence having at least 80% identity therewith. Petition 870250084408, dated 09 / 19 / 2025, page 140 / 297 129 / 214 at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with the same.

[00230] In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain comprises a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00231] In some embodiments, the second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00232] In some embodiments, the first antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith; and a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or Petition 870250084408, dated 09 / 19 / 2025, page 141 / 297 130 / 214 a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and the second antigen-binding domain comprises a heavy chain variable region domain comprising an amino acid sequence of SEQ ID 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and a light chain variable region domain comprising an amino acid sequence of SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00233] In some embodiments, the biparatopic antibody or antibody-drug conjugate comprises a full-size IgG1 antibody comprising the first antigen-binding domain, and the antibody or antibody-drug conjugate comprises two polypeptides comprising a first antigen-binding domain heavy chain variable region domain of SEQ ID NO: 96, a first linker of SEQ ID NO: 152, a second antigen-binding domain heavy chain variable region domain of SEQ ID NO: 97, a second linker of SEQ ID NO: 153, and a light chain variable region of SEQ ID NO: 99. In some embodiments, the antibody or antibody-drug conjugate comprises two polypeptides comprising a light chain variable region domain of SEQ ID NO: 98.In some embodiments, the antibody-drug conjugate comprises two polypeptides comprising a first antigen-binding domain with a variable region heavy chain of SEQ ID NO: 96, a first ligand with SEQ ID NO: 152, and a second antigen-binding domain with a variable region heavy chain of SEQ ID NO: 97. Petition 870250084408, dated 09 / 19 / 2025, page 142 / 297 131 / 214 a second linker of SEQ ID NO: 153, and a variable light chain region of SEQ ID NO: 99, and the antibody or antibody-drug conjugate also comprises two polypeptides comprising a variable light chain region domain of antibody of SEQ ID NO: 98. In some embodiments, the full-size IgG1 light and heavy chains comprise a constant region domain of the IgG1 isotype.

[00234] In some embodiments, the second antigen-binding domain is a scFv comprising a first heavy chain domain comprising SEQ ID NO: 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain is a scFv comprising a first heavy chain domain comprising SEQ ID NO: 97.

[00235] In some embodiments, the second antigen-binding domain is a scFv comprising a variable region light chain domain comprising SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second antigen-binding domain is a scFv comprising a variable region light chain domain comprising SEQ ID NO: 99.

[00236] In some embodiments of the antibody-drug conjugate, the second antigen-binding domain is an scFv comprising a first heavy chain domain comprising SEQ ID NO: 97; and a variable region light chain domain comprising SEQ ID NO: 99.

[00237] In some embodiments, the antibody or antibody-drug comprises a full-size IgG antibody that with Petition 870250084408, dated 09 / 19 / 2025, page 143 / 297 132 / 214 comprises the first antigen-binding domain, and the antigen-binding domain antibody comprises an scFv, and the antibody or antibody-drug conjugate comprises two polypeptides comprising, from the N to C termini, a first antibody heavy chain variable region domain of SEQ ID NO: 96, an IgG1 isotype constant region domain of SEQ ID NO: 148, a first linker of SEQ ID NO: 152, a second antibody heavy chain variable region domain of SEQ ID NO: 97, a second linker of SEQ ID NO: 153, and a light chain variable region of SEQ ID NO: 99.In some embodiments, the antibody or antibody-drug conjugate comprises two polypeptides comprising, from the N to C termini, a first antibody heavy chain variable region domain of SEQ ID NO: 96, an IgG1 isotype constant region domain of SEQ ID NO: 148, a first linker of SEQ ID NO: 152, a second antibody light chain variable region of SEQ ID NO: 99, a second linker of SEQ ID NO: 153, and a heavy chain variable region domain of SEQ ID NO: 97.

[00238] In some embodiments, the antibody or antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprising an scFv, and the antibody or antibody-drug conjugate comprises two polypeptides comprising, from the N to C termini, a first antibody variable light chain domain of SEQ ID NO: 98, and a first antibody constant region light chain domain of SEQ ID NO: 149.

[00239] In some embodiments, the antibody or antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprising an scFv, and the antibody or antibody-drug conjugate comprises four polypeptides that Petition 870250084408, dated 09 / 19 / 2025, page 144 / 297 133 / 214 comprise: two polypeptides comprising, from the N to C termini, a first variable region domain of the antigen-binding domain heavy chain of SEQ ID NO: 96, a constant region domain of the IgG1 isotype of SEQ ID NO: 148, a first linker of SEQ ID NO: 152, a second variable region domain of the antigen-binding domain heavy chain of SEQ ID NO: 97, a second linker of SEQ ID NO: 153, and a variable region of the light chain of SEQ ID NO: 99; two polypeptides comprising, from the N to C termini, a first variable light chain domain of the antigen-binding domain of SEQ ID NO: 98, and a first constant region domain of the antigen-binding domain light chain of SEQ ID NO: 149.

[00240] In some embodiments, the antibody or antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprising an scFv, and the antibody or antibody-drug conjugate comprises four polypeptides comprising: two polypeptides comprising, from the N to C termini, a first antigen-binding domain variable region heavy chain domain of SEQ ID NO: 96, an IgG1 isotype constant region domain of SEQ ID NO: 148, a first linker of SEQ ID NO: 152, a second antigen-binding domain variable region light chain of SEQ ID NO: 99, a second linker of SEQ ID NO: 153, and a variable region heavy chain domain of SEQ ID NO: 97;two polypeptides comprising, from the N to C termini, a first variable light chain domain of antigen-binding domain with SEQ ID NO: 98, and a first constant region light chain domain of antigen-binding domain with SEQ ID NO: 149.;

[00241] In some embodiments, the antibody or antibody conjugate Petition 870250084408, dated 09 / 19 / 2025, page 145 / 297 134 / 214 The drug-body complex comprises two polypeptides comprising a sequence with SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and two polypeptides comprising a sequence with SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00242] In some embodiments, the antibody or antibody-drug conjugate comprises two polypeptides comprising a SEQ ID NO: 100 sequence; and two polypeptides comprising a SEQ ID NO: 101 sequence.

[00243] The invention provides antibodies and antibody-drug conjugates comprising a first antigen-binding domain that specifically binds to a first 5T4 epitope; a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; wherein the first antigen-binding domain is operationally linked to the second antigen-binding domain; and a chemotherapeutic agent, wherein the first antigen-binding domain comprises a full-size IgG antibody and the second antigen-binding domain comprises an scFv, and the antibody or antibody-drug conjugate comprises: (a) two polypeptides comprising at least one heavy chain variable region domain comprising: a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1; a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 2;a CDR3 HC sequence comprising an amino acid sequence of SEQ ID NO: 3; and wherein the polypeptide also comprises an amino acid sequence of; Petition 870250084408, dated 09 / 19 / 2025, pp. 146 / 297 135 / 214 (a) two polypeptides comprising at least one variable region light chain domain comprising: an LC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 7; an LC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 8; an LC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 9; and wherein the polypeptide also comprises an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00244] The invention provides antibodies or antibody-drug conjugates comprising a first antigen-binding domain that specifically binds to a first 5T4 epitope; a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; and a chemotherapeutic agent, wherein the first antigen-binding domain comprises a full-size IgG antibody and the second antigen-binding domain comprises an scFv, and the antibody or antibody-drug conjugate comprises: (a) two polypeptides comprising at least one heavy chain variable region domain comprising: a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 4; a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5;a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6; and wherein the po; Petition 870250084408, dated 09 / 19 / 2025, pp. 147 / 297 136 / 214 lipeptide also comprises an amino acid sequence of SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it; and (b) two polypeptides comprising at least one variable region light chain domain comprising: a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 10; a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 11; and a CDR3 sequence of LC comprising an amino acid sequence of SEQ ID NO: 12; and wherein the polypeptide also comprises an amino acid sequence with SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity with it.

[00245] The present invention provides an antibody or antibody-drug conjugate comprising a first antigen-binding domain that specifically binds to a first 5T4 epitope; a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; and a chemotherapeutic agent, wherein the first antigen-binding domain comprises a full-size IgG antibody and the second antigen-binding domain comprises an scFv, and the antibody or antibody-drug conjugate comprises: (a) two polypeptides comprising a first variable region heavy chain domain comprising: a CDR1 HC sequence comprising an amino acid sequence of SEQ ID NO: 1; a CDR2 HC sequence comprising an amino acid sequence of SEQ ID NO: 2;a sequence of HC CDR3s that you buy; Petition 870250084408, dated 09 / 19 / 2025, pp. 148 / 297 137 / 214 contains an amino acid sequence with SEQ ID NO: 3; and at least a second heavy chain variable region domain comprising: a CDR1 sequence of HC comprising an amino acid sequence with SEQ ID NO: 4; a CDR2 sequence of HC comprising an amino acid sequence with SEQ ID NO: 5; a CDR3 sequence of HC comprising an amino acid sequence with SEQ ID NO: 6; and a light chain variable region domain comprising: a CDR1 sequence of LC comprising an amino acid sequence with SEQ ID NO: 7; a CDR2 sequence of LC comprising an amino acid sequence with SEQ ID NO: 8; a CDR3 sequence of LC comprising an amino acid sequence with SEQ ID NO: 9; and wherein the polypeptide also comprises an amino acid sequence with SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it;and (b) two polypeptides comprising a variable region light chain domain comprising: an LC CDR1 sequence comprising an amino acid sequence of SEQ ID NO: 10; an LC CDR2 sequence comprising an amino acid sequence of SEQ ID NO: 11; an LC CDR3 sequence comprising an amino acid sequence of SEQ ID NO: 12; and wherein the polypeptide also comprises an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

[00246] The invention provides antibodies or antibody-drug conjugates comprising a first antigen-binding domain that binds specifically to a first 5T4 epitope; a second antigen-binding domain that binds specifically to Petition 870250084408, dated 09 / 19 / 2025, p. 149 / 297 138 / 214 a second 5T4 epitope that is not the same as the first 5T4 epitope; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; and a chemotherapeutic agent, wherein the first antigen-binding domain comprises a full-size IgG antibody and the second antigen-binding domain comprises an scFv, and the antibody or antibody-drug conjugate comprises: (a) two polypeptides comprising a first variable region heavy chain domain comprising: a CDR1 HC sequence comprising an amino acid sequence of SEQ ID NO: 1; a CDR2 HC sequence comprising an amino acid sequence of SEQ ID NO: 2; a CDR3 HC sequence comprising an amino acid sequence of SEQ ID NO: 3; and at least a second variable region heavy chain domain comprising: a CDR1 HC sequence comprising an amino acid sequence of SEQ ID NO: 4;a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5; a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6; and a variable region light chain domain comprising: a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 10; a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 11; a CDR3 sequence of LC comprising an amino acid sequence of SEQ ID NO: 12; and wherein the polypeptide also comprises an amino acid sequence of SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and (b) two polypeptides comprising a variable region light chain domain comprising: an LC CDR1 sequence comprising an amino acid sequence; Petition 870250084408, dated 09 / 19 / 2025, pp. 150 / 297 139 / 214 amino acid of SEQ ID NO: 7; a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 8; a CDR3 sequence of LC comprising an amino acid sequence of SEQ ID NO: 9; and wherein the polypeptide also comprises an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it. Therapeutic Agents

[00247] The antigen- and antibody-binding domains specific for 5T4 described may be conjugated to a therapeutic agent or effector molecule, including, but not limited to, molecules in which there is a covalent bond of the therapeutic agent to the antigen- or antibody-binding domain. A therapeutic agent is an agent with a specific biological activity directed against a specific target molecule or a cell bearing a target molecule. A person skilled in the art will understand that therapeutic agents may include various drugs, such as vinblastine, daunomycin and the like, cytotoxins, such as native or modified Pseudomonas exotoxin or diphtheria toxin, encapsulating agents (such as liposomes) containing pharmacological compositions, radioactive agents, such as 125I, 32P, 14C, 3H and 35S and other markers, target groups and ligands.

[00248] In some modalities, the therapeutic agent is a chemotherapeutic agent.

[00249] The choice of a specific therapeutic agent depends on the specific target molecule or cell and the desired biological effect. Thus, for example, the therapeutic agent may be a cytotoxin used to cause the death of a specific target cell (such as a tumor cell). On the other hand, when a non-lethal biological response is desired, the therapeutic agent may be conjugated to a Petition 870250084408, dated 09 / 19 / 2025, pp. 151 / 297 140 / 214 non-lethal pharmacological agent or a liposome containing a non-lethal pharmacological agent.

[00250] Effector molecules can be linked to an antigen- or antibody-binding domain of interest using various means known to those skilled in the art. Both covalent and non-covalent linking methods can be used. The procedure for linking an effector molecule to an antibody varies depending on the chemical structure of the effector. Polypeptides typically contain a variety of functional groups, such as carboxylic acid (COOH), free amine groups (—NH2), or sulfhydryl groups (—SH), which are available for reaction with a suitable functional group on an antibody, resulting in the binding of the effector molecule. Alternatively, the antigen- or antibody-binding domain is derivatized to expose or link additional reactive functional groups. Derivatization may involve the attachment of any one of several known ligand molecules. The ligand can be any molecule used to link the antibody to the effector molecule.The ligand is capable of forming covalent bonds with both the protein and the effector molecule. Suitable ligands are well known to those skilled in the art and include, but are not limited to, linear or branched chain carbon ligands, heterocyclic carbon ligands, or peptide ligands. When the protein and effector molecule are polypeptides, the ligands can be attached to the constituent amino acids via their side groups (such as via a disulfide bond to cysteine) or to the amino and carboxyl groups of the alpha carbon of the terminal amino acids.

[00251] In some circumstances, it is desirable to release the effector molecule from the antigen- or antibody-binding domain when the immunoconjugate reaches its target site. Therefore, in these circumstances, immunoconjugates will comprise cleavable linkages in the vicinity of the target site. Cleavage of the ligand to release the effector molecule from Petition 870250084408, dated 09 / 19 / 2025, page 152 / 297 141 / 214 antibody may be induced by enzymatic activity or by the conditions to which the immunoconjugate is subjected, either within the target cell or in the vicinity of the target site.

[00252] One skilled in the art will be able to determine a suitable method for linking a given agent to an antibody or other polypeptide.

[00253] In some respects, the chemotherapeutic agent is conjugated to at least one of the first antigen-binding domains or second antigen-binding domains of biparatopic antibodies, described herein by means of a ligand. In some respects, the chemotherapeutic agent is an auristatin. In some respects, the auristatin is selected from the group consisting of auristatin E (AE), monomethyl auristatin D (MMAD), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and synthetic analogs of dolastatin. In some respects, the ligand is a cleavable ligand. In other respects, the ligand is a non-cleavable ligand.

[00254] The biparatopic antibody-drug conjugates (ADCs) against 5T4 of the present invention comprise a first antigen-binding domain that specifically binds to a first 5T4 epitope, a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope, wherein the first antigen-binding domain is operably linked to the second antigen-binding domain, and is conjugated to a cytotoxic or immunosuppressive agent, such that the resulting ADC exerts a cytotoxic or cytostatic effect on a cancer cell expressing 5T4. Thus, the biparatopic anti-5T4 drug-antibody conjugate exerts a cytotoxic or cytostatic effect on cancer cells expressing 5T4. In one embodiment, the anti-5T4 ADC is internalized and accumulates within a cell that expresses 5T4, where the ADC exerts a therapeutic effect (by Petition 870250084408, dated 09 / 19 / 2025, page 153 / 297 142 / 214 example, a cytotoxic, cytostatic or immunosuppressive effect).

[00255] Examples of suitable moieties for conjugation with antigen-binding domains and antibodies include chemotherapeutic agents, prodrug-converting enzymes, radioactive isotopes or compounds, or toxins. In exemplary embodiments, the anti-5T4 antibody, or an antigen-binding moiety thereof, is conjugated to an auristatin, for example, MMAF or MMAE. Any agent that exerts a therapeutic effect on cancer cells or activated immune cells may be used as a therapeutic agent for conjugation with an anti-5T4 antibody or a derivative thereof (see, for example, WO 2004 / 010957, Drug Conjugates and Their Use for Treating Cancer, An Autoimmune Disease or an Infectious Disease (above) and US Provisional Application No. 60 / 400.403 (above)). Typically, the therapeutic agent is a cytotoxic agent.In some embodiments, an anti-5T4 antibody-drug conjugate comprises more than one therapeutic agent per conjugate, for example, from about 1 to about 20 therapeutic agents per conjugate (commonly referred to as the drug-antibody ratio, or DAR).

[00256] In some embodiments, the anti-5T4 antibody, or an antigen-binding portion thereof, is conjugated to an auristatin. Auristatins have been shown to interfere with microtubule dynamics, GTP hydrolysis and / or nuclear and cell division, and possess anticancer and / or antifungal activity.

[00257] An anti-5T4 antibody or antigen-binding domain of the invention may be conjugated to at least one auristatin. Auristatins represent a group of dolastatin analogs that generally demonstrate anticancer activity by interfering with microtubule dynamics and GTP hydrolysis, thereby inhibiting cell division. For example, Auristatin E (described in U.S. Patent No. 5,635,483, incorporated herein by reference) is an analog of... Petition 870250084408, dated 09 / 19 / 2025, page 154 / 297 143 / 214 synthetic logo of the marine natural product dolastatin 10, a compound that inhibits tubulin polymerization by binding to the same site on tubulin as the anticancer drug vincristine (GR Pettit, Prog. Chem. Org. Nat. Prod, 70: 1-79 (1997)). Dolastatin 10, auristatin PE and auristatin E are linear peptides with four amino acids, three of which are unique to the dolastatin class of compounds. Examples of the auristatin subclass of mitotic inhibitors include, among others, monomethyl auristatin D (MMAD or auristatin D derivative), monomethyl auristatin E (MMAE or auristatin E derivative), monomethyl auristatin F (MMAF or auristatin F derivative), auristatin F phenylenediamine (AFP), auristatin EB (AEB), auristatin EFP (AEFP), and 5-benzoylvaleric acid ester-AE (AEVB). The synthesis and structure of auristatin derivatives are described in U.S. Patent Application Publications Nos. 2003-0083263, 20050238649, and 2005-0009751.International Patent Publication No. WO 04 / 010957, International Patent Publication No. WO 02 / 088172 and U.S. Patents Nos. 6,323,315; 6,239,104; 6,034,065; 5,780,588; 5,665,860; 5,663,149; 5,635,483; 5,599,902; 5,554,725; 5,530,097; 5,521,284; 5,504,191; 5,410,024; 5,138,036; 5,076,973; 4,986,988; 4,978,744; 4,879,278; 4,816,444; and 4,486,414, each of which is incorporated herein by reference.

[00258] In some embodiments, an anti-5T4 antibody or antigen-binding domain is conjugated to at least one MMAF (monomethyl auristatin F) by a ligand such as, but not limited to, maleimidocaproyl (mc-MMAF). An anti-5T4 ADC may have a drug-antibody ratio (DAR) of 2, 4, 6, or 8. Notably, the DAR of an ADC may range from 0 to 8, although higher loadings, e.g., 10, 12, or 14, are also possible. Monomethyl auristatin F (MMAF) inhibits cell division by blocking tubulin polymerization. It possesses a charged C-terminal phenylalanine residue that performs Petition 870250084408, dated 09 / 19 / 2025, pp. 155 / 297 144 / 214 its cytotoxic activity compared to its uncharged counterpart, MMAE. Due to its toxicity, it cannot be used as a drug on its own, but it can be linked to a monoclonal antibody (mAb) that targets it to cancer cells. In one embodiment, the ligand for the anti-5T4 antibody is stable in the extracellular fluid, but is cleaved by cathepsin as soon as the conjugate enters the tumor cell, thereby activating the antimitotic mechanism.

[00259] In some embodiments, the anti-5T4 antibody or antigen-binding domain of the invention is conjugated to at least one MMAE (monomethyl auristatin E). Monomethyl auristatin E (MMAE, vedotin) inhibits cell division by blocking tubulin polymerization. Due to its toxicity, it often cannot be used as a drug on its own. In recent developments in cancer therapy, it is linked to a monoclonal antibody (mAb) that recognizes the expression of a specific marker on cancer cells and targets the MMAE to the cancer cells. In some embodiments, the ligand that links MMAE to the anti-5T4 antibody or to the antigen-binding domain is stable in the extracellular fluid (i.e., the medium or environment external to the cells), but is cleaved by cathepsin as soon as the ADC binds to the specific antigen of the cancer cell and penetrates the cancer cell, thus releasing the toxic MMAE and activating the potent antimitotic mechanism.

[00260] In some embodiments, the anti-5T4 antibody, or its antigen-binding moiety, is conjugated to an auristatin, which is MMAF. In some embodiments, the anti-5T4 ADC is covalently linked to one or more molecules of monomethyl auristatin F (MMAF). In some embodiments, to generate the anti-5T4 ADC covalently linked to one or more molecules of MMAF, the interchain disulfide bonds of the ADC are reduced to sulfhydryl groups. The MMAF is then coupled to the antibody through these sulfhydryl groups. In some embodiments, to generate the anti-5T4 ADC covalently linked to one or more molecules of MMAF, the interchain disulfide bonds of the ADC are reduced to sulfhydryl groups. The MMAF is then coupled to the antibody through these sulfhydryl groups. Petition 870250084408, dated 09 / 19 / 2025, pp. 156 / 297 145 / 214 but modalities, the anti-5T4 ADC is generated using a non-cleavable linker, namely a non-cleavable maleimidocaproyl (mc) linkage.

[00261] ADCs that can be tagged with a detectable or functional marker. Detectable tracers include, but are not limited to, radiotracers such as the isotopes .sup.2H, .sup.3H, .sup.11C, .sup.13C, .sup.14C, .sup.32P, .sup.33S, .sup.34S, .sup.35S, .sup.36S, .sup.36Cl, .sup.51Cr, .sup.57Co, .sup.58Co, .sup.59Fe, .sup.90Y, .sup.121I, .sup.124I, .sup.125I, .sup.131I, .sup.211At, .sup.198Au, .sup.67Cu, .sup.225Ac, .sup.213Bi, .sup.99Tc, and .sup.186Re, which can be linked to the antibodies of the invention using conventional chemistry known in antibody imaging techniques. The markers also include fluorescent markers and markers conventionally used in magnetic resonance imaging and computed tomography techniques. They also include enzymatic markers, such as horseradish peroxidase.The markers also include chemical moieties, such as biotin, which can be detected by binding to a specific detectable cognate moiety, for example, labeled avidin.

[00262] Functional markers may also include substances designed to be targeted to the site of a tumor to cause the destruction of tumor tissue. Such functional markers include cytotoxic drugs, such as 5-fluorouracil or ricin, and enzymes, such as bacterial carboxypeptidase or nitroreductase, which are capable of converting prodrugs into active drugs at the site of a tumor.

[00263] As will be understood by those skilled in the art, the agents described above, as well as other suitable agents, may be conjugated or linked to an anti-5T4 antibody, such as the antibodies represented in Figures 1A and 1B, in any manner suitable to produce an anti-5T4 ADC of the present invention. Petition 870250084408, dated 09 / 19 / 2025, pp. 157 / 297 146 / 214 For example, and without limitation, in various embodiments of the present invention, the anti-5T4 antibody and the agent(s) can be covalently linked and / or conjugated using linker compounds, spacers and / or extenders, which in various embodiments of the present invention are cleavable or non-cleavable, and result in the internalization of the therapeutic agent(s) by the target cell.

[00264] In one embodiment, the anti-5T4 antibody or antigen-binding domain is conjugated to MMAF using a non-cleavable maleimidocaproyl linker.

[00265] Techniques for conjugating therapeutic agents to proteins, and in particular to antibodies, are known in the art (see, for example, Arnon et al., Monoclonal Antibodies For Immunotargeting Of. Drugs n Cancer Therapy, in Monoclonal Antibodies and Cancer Therapy (Reisfeld et al. eds., Alan R. Liss, Inc., 1985); Hellstrom et al., Antibodies For Drug Delivery, in Controlled Drug Administration (Robinson et al. eds., Marcel Dekker, Inc., 2nd ed., 1987); Thorpe, Antibody Carriers Of. Cytotoxic Agents In Cancer Therapy: A Review, in Monoclonal Antibodies '84: Biological and Clinical Applications (Pinchera et al. eds., 1985); Analysis, Results, and Future Prospective of the Therapeutic Use of Radiolabeled Antibody In Cancer Therapy, in Antibodies Monoclonal Antibodies for Cancer Detection and Therapy (Baldwin et al. eds., Academic Press, 1985); and Thorpe et al., 1982, Immunol. Rev. 62:119-58. See also, for example, PCT publication WO 89 / 12624).

[00266] In some embodiments, the ADC comprises a binding region between the cytotoxic agent and the antibody- or antigen-binding domain. For example, such binding compounds, spacers, and / or extenders include, but are not limited to, the following: aminobenzoic acid spacers (see, for example, and without limitation, U.S. Patents Nos. 7,091,186 and 7,553,816, each of which Petition 870250084408, dated 09 / 19 / 2025, pp. 158 / 297 147 / 214 which is incorporated herein by reference in its entirety); maleimidocaproyl; p-aminobenzylcarbamoyl (PAB); lysosomal enzyme-cleavable ligands (see, for example, and without limitation, U.S. Patent No. 6,214,345, incorporated herein by reference in its entirety); maleimidocaproyl-polyethylene 20 glycol (MC(PEG)6-OH); N-methylvaline citrulline; N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) (see, for example, and without limitation, Yoshitake et al. (1979) Eur. J. Biochem., 101, 395-399, incorporated herein by reference in its entirety); N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) (see, for example, and without limitation, U.S. Patent No. 4,563,304, incorporated herein by reference in its entirety); N-succinimidyl 4-(2-pyridylthio)pentanoate (SPP); valine-citrulline; and other binding, spacer and / or extender compounds (see, for example, and without limitation, U.S. Patents Nos. 7,090,843, 7,223,837 and 7,659).241, and U.S. Patent Publications Nos. 2004 / 0018194, 2004 / 0121940, 2006 / 0116422, 2007 / 0258987. 2008 / 0213289, 2008 / 0241128, 2008 / 0311136, 2008 / 0317747 and 2009 / 0010945, each of which is incorporated herein by reference in its entirety). In general, techniques for linking and / or conjugating the agents described above, as well as other agents, to specific linking members of the present invention, particularly antibodies and their fragments, are known in the art. See, for example, and without limitation, Hellstrom et al., Antibodies For Drug Delivery, in Controlled Drug Delivery (2nd ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985), each of which is incorporated herein by reference in its entirety.

[00267] A range of different reactions are available for li Petition 870250084408, dated 09 / 19 / 2025, pp. 159 / 297 148 / 214 Covalent linkage of drugs to antibodies or antigen-binding domains. This is generally accomplished by the reaction of amino acid residues of the antibody molecule, including the amine groups of lysine, the free carboxylic acid groups of glutamic and aspartic acids, the sulfhydryl groups of cysteine, and the various moieties of aromatic amino acids. One of the most commonly used non-specific methods of covalent linkage is the carbodiimide reaction to link a carboxyl (or amino) group of a compound to amino (or carboxyl) groups of the antibody. Additionally, bifunctional agents such as dialdehydes or imidoesters have been used to link the amino group of a compound to amino groups of the antibody molecule. Also available for drug-to-antibody linkage is the Schiff base reaction. This method involves the periodate oxidation of a drug containing glycol or hydroxyl groups, thus forming an aldehyde that is then reacted with the antibody molecule.The binding occurs through the formation of a Schiff base with amino groups of the antibody molecule. Isothiocyanates can also be used as coupling agents for the covalent binding of drugs to antibodies. Other techniques are known to those skilled in the art and fall within the scope of the present invention. Non-limiting examples of such techniques are described, for example, in U.S. Patents Nos. 5,665,358; 5,643,573; and 5,556,623, which are incorporated herein by reference in their entirety.

[00268] In certain embodiments, an intermediate, which is the precursor of the ligand, reacts with the drug under appropriate conditions. In certain embodiments, reactive groups are used in the drug and / or the intermediate. The product of the reaction between the drug and the intermediate, or the derivatized drug, is subsequently reacted with the anti-5T4 antibody under appropriate conditions.

[00269] Other examples of conjugation methods are described Petition 870250084408, dated 09 / 19 / 2025, pp. 160 / 297 149 / 214 in U.S. Patents Nos. 5,665,358; 5,643,573; and 5,556,623, which are incorporated herein by reference in their entirety.

[00270] In certain embodiments, an intermediate, which is the precursor of the ligand, reacts with the drug under appropriate conditions. In certain embodiments, reactive groups are used in the drug and / or the intermediate. The product of the reaction between the drug and the intermediate, or the derivatized drug, is subsequently reacted with the anti-5T4 antibody under appropriate conditions.

[00271] Other examples of conjugation methods are described in U.S. Patents Nos. 5,665,358; 5,643,573; and 5,556,623, which are incorporated herein by reference in their entirety.

[00272] In certain embodiments, an intermediate, which is the precursor of the ligand, reacts with the drug under appropriate conditions. No. 7,837,980 (Seattle Genetics), Carter and Senter (2008) Cancer J, 14(3):154, as well as US Published Applications No. 20040157782 A1 and 2005-0238649 and International Patent Application No. PCT / US04 / 038392.

[00273] In certain embodiments, anti-5T4 ADCs can be purified to obtain ADCs with a desired drug-antibody ratio (DAR). In one embodiment of the invention, the formulation contains a mixture of anti-5T4 ADCs comprising anti-5T4 ADCs with a desired average drug-antibody ratio (DAR), for example, an average DAR of about 3. In another embodiment of the invention, the formulation comprises a mixture of ADCs comprising anti-5T4 ADCs with a desired DAR range, for example, a DAR of about 2-4, or about 2-8, or about 4-8.

[00274] In one embodiment, the formulation contains a mixture of ADCs where 70% of the ADCs present have a species loaded with Petition 870250084408, dated 09 / 19 / 2025, pp. 161 / 297 150 / 214 drug of 8 or less, and where the ADC comprises an anti-5T4 antibody and an auristatin. Alternatively, 75% of the ADCs present have a drug-loaded species of 8 or less; 80% of the ADCs present have a drug-loaded species of 8 or less; 85% of the ADCs present have a drug-loaded species of 4 or less; 90% of the ADCs present have a drug-loaded species of 8 or less; or 95% of the ADCs present have a drug-loaded species of 8 or less. Polynucleotides and Vectors

[00275] The invention provides polynucleotides and polynucleotide systems comprising one or more polynucleotides encoding the anti-5T4 antibodies, antigen-binding domains and receptors described herein.

[00276] In some embodiments, the polynucleotides or polynucleotide systems described herein comprise sequences encoding any of the light chain CDR sequences and / or heavy chain CDR sequences of the biparatopic anti5T4 antibodies described herein.

[00277] In some embodiments, the polynucleotides or polynucleotide systems described herein comprise sequences encoding either of the light and heavy chains of the biparatopic anti-5T4 antibodies described herein.

[00278] In some embodiments, the polynucleotides or polynucleotide systems described herein comprise sequences as set forth in any of Tables 4 to 7.

[00279] The invention provides a first polynucleotide encoding a first heavy chain of an anti-5T4 antigen-binding domain and a second polynucleotide encoding a light chain of an anti-5T4 antigen-binding domain. In some embodiments, the first and second polynucleotides are separate molecules. Petition 870250084408, dated 09 / 19 / 2025, page 162 / 297 151 / 214 of the. Alternatively, the first and second polynucleotides may be part of a single contiguous polynucleotide molecule.

[00280] In some embodiments, the invention provides a first polynucleotide encoding a first heavy chain of the anti-5T4 antigen-binding domain, a linker, and a second anti-5T4 antigen-binding domain; and a second polynucleotide encoding a light chain of the first anti-5T4 antigen-binding domain. In some embodiments, the invention provides a single contiguous polynucleotide molecule encoding a first heavy chain of the anti-5T4 antigen-binding domain, a first light chain of the anti-5T4 antigen-binding domain, and a second anti-5T4 antigen-binding domain.

[00281] In some embodiments, the first polynucleotide encodes a sequence of a first polypeptide comprising, from the N-terminal to the C-terminal, a first heavy chain of the anti-5T4 antigen-binding domain, a linker, and a second anti-5T4 antigen-binding domain. In some embodiments, the first polynucleotide encodes a sequence of a first polypeptide comprising, from the N-terminal to the C-terminal, a second anti-5T4 antigen-binding domain, a linker, and a first heavy chain of the anti-5T4 antigen-binding domain. In some embodiments, the first polynucleotide encodes a sequence of a first polypeptide comprising, from the N-terminal to the C-terminal, a second anti-5T4 antigen-binding domain, a linker, and a first heavy chain of the anti-5T4 antigen-binding domain. In some embodiments, the first polynucleotide comprises a nucleotide sequence with SEQ ID NO: 144 or 145.In some embodiments, the first polynucleotide comprises a sequence of nucleotides with SEQ ID NO: 144 and 150. In some embodiments, the first polynucleotide comprises a sequence of nucleotides. Petition 870250084408, dated 09 / 19 / 2025, page 163 / 297 152 / 214 of SEQ ID NO: 145 and 150. In some embodiments, the first polynucleotide comprises a nucleotide sequence of SEQ ID NO: 142.

[00282] In some embodiments, the second polynucleotide encodes a second polypeptide comprising a first light chain of the anti-5T4 antigen-binding domain. In some embodiments, the second polynucleotide comprises a nucleotide sequence with SEQ ID NO: 146 or 147. In some embodiments, the second polynucleotide comprises a nucleotide sequence with SEQ ID NO: 146 and 151. In some embodiments, the second polynucleotide comprises a nucleotide sequence with SEQ ID NO: 147 and 151. In some embodiments, the second polynucleotide comprises a nucleotide sequence with SEQ ID NO: 143.

[00283] In some embodiments, the first polynucleotide encodes a polypeptide comprising a sequence with SEQ ID NO: 100, or a sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith. In some embodiments, the second polynucleotide encodes a polypeptide comprising a sequence with SEQ ID NO: 101, or a sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity therewith.

[00284] In some embodiments, the polynucleotide sequences encoding each of the first and second polypeptides are operably linked to one or more promoters. For example, sequences of the polypeptides may be operably linked (under the control of) to the same promoter and separated by one or more elements that produce distinct polypeptides, such as self-cleaving polypeptides, entry sites into the inner ribosome, and the like.

[00285] In alternative modes, the sequences of the first or Petition 870250084408, dated 09 / 19 / 2025, pp. 164 / 297 153 / 214 of the second polynucleotides encoding the first or second polypeptides are under the control of separate promoters. For example, each of the first and second polynucleotides can be cloned into a separate expression vector, each vector comprising its own promoter and / or regulatory sequences. In some embodiments, the promoters operably linked to each of the first and second polynucleotides are the same. In some embodiments, the promoters operably linked to each of the first and second polynucleotides are not the same.

[00286] In some embodiments, the polynucleotides of the present invention are prepared using PCR techniques, using procedures and methods known to one skilled in the art. In some embodiments, the procedure involves the ligation of two different DNA sequences (see, for example, Current Protocols in Molecular Biology, eds. Ausubel et al., John Wiley & Sons, 1992).

[00287] With the antigen-, antibody-, and receptor-binding domains described herein, a technician can easily construct a variety of clones containing functionally equivalent nucleic acids, such as nucleic acids that differ in sequence but encode the same protein sequence. Thus, the present invention provides nucleic acids that encode antibodies for the same.

[00288] A polynucleotide sequence is operably linked when it is placed in a functional relationship with another polynucleotide sequence. For example, a polynucleotide presequence or secretory leader is operably linked to a nucleic acid encoding a polypeptide if it is expressed as a preprotein 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 affects the transcription of the sequence. Petition 870250084408, dated 09 / 19 / 2025, pp. 165 / 297 154 / 214 operably linked to a coding sequence if positioned to facilitate translation. Generally, operably linked means that the polynucleotide sequences being linked are contiguous and, in the case of a secretory leader, contiguous and in the same reading frame. However, enhancers are optionally contiguous. Linkage can be achieved, for example, by linkage at convenient restriction sites. If such sites do not exist, synthetic oligonucleotide adapters, linkers, or other methods known in the art can be used. In another embodiment, operably linked also refers to the functional pairing of distinct amino acid, peptide, or protein sequences, as in the combination of the first heavy chain of the anti-5T4 antigen-binding domain and the second anti-5T4 antigen-binding domain described herein, which are operably linked, optionally by means of linker sequences also described herein.For example, the first heavy chain of the anti-5T4 antigen-binding domain is operably linked to the second anti-5T4 antigen-binding domain via a linker sequence, as described herein.

[00289] The invention provides vectors comprising polynucleotides that comprise sequences encoding the 5T4 antigen-binding domains, antibodies and receptors described herein.

[00290] The terms vector, cloning vector, and expression vector mean the vehicle by which a DNA or RNA sequence (e.g., a foreign gene) can be introduced into a host cell so as to transform the host and promote the expression (e.g., transcription and translation) of the introduced sequence. Vectors include plasmids, phages, viruses, etc.

[00291] The terms express and expression mean to allow or cause the information in a gene or DNA sequence to manifest itself, for example, by producing a protein through the activation of Petition 870250084408, dated 09 / 19 / 2025, pp. 166 / 297 155 / 214 Cellular functions involved in the transcription and translation of a gene or corresponding DNA sequence. A DNA sequence is expressed in or by a cell to form an expression product, such as a protein. The expression product itself, for example, the resulting protein, can also be considered expressed by the cell. An expression product can be characterized as intracellular, extracellular, or transmembrane. The term intracellular means something that is inside a cell. The term extracellular means something that is outside a cell. The term transmembrane means something that has an extracellular domain outside the cell, a portion embedded in the cell membrane, and an intracellular domain inside the cell.

[00292] In some embodiments, the polynucleotides of the present invention are inserted into expression vectors (i.e., a nucleic acid construct) to enable the expression of the polypeptides described herein.

[00293] In some embodiments, the expression vector of the present invention includes additional sequences that make it suitable for replication and integration in prokaryotes. In some embodiments, the expression vector of the present invention includes additional sequences that make it suitable for replication and integration in eukaryotes. In some embodiments, the expression vector of the present invention includes a transport vector that makes it suitable for replication and integration in both prokaryotes and eukaryotes. For example, such vectors may include selectable markers appropriate for eukaryotic and prokaryotic cells. Suitable markers will be evident to persons skilled in the art.

[00294] In some embodiments, cloning vectors comprise transcription and translation initiation sequences (e.g., promoters, enhancer) and transcription terminators and Petition 870250084408, dated 09 / 19 / 2025, pp. 167 / 297 156 / 214 translation (e.g., polyadenylation signals) to increase the expression of polypeptides expressed from them. Suitable translation terminators include, but are not limited to, bovine growth hormone (BGH polyA) polyadenylation signals and the like. Suitable promoters will be evident to those skilled in the art and include the CMV promoter, the actin promoter, and the like.

[00295] In some embodiments, the expression vectors of the present invention may also include additional polynucleotide sequences that allow, for example, the translation of multiple proteins from a single mRNA, such as an internal ribosome entry site (IRES) and sequences for genomic integration of the chimeric promoter polypeptide.

[00296] In some embodiments, the expression vectors of the present invention include elements that enhance the expression of the antibodies of the invention. Such features include, among others, the choice of promoter and polyadenylation. In some embodiments, the polyadenylation sequence is a bovine growth hormone (BGH) polyadenylation sequence. In some embodiments, the promoter comprises a constitutively active promoter. In some embodiments, the promoter comprises a cytomegalovirus (pCMV) promoter. The promoters may, in some embodiments, be combined with additional elements to promote the expression of the recombinant proteins of the invention, such as introns (e.g., rabbit beta-globin intron, EF1a intron, and the like) and enhancer elements (immediate early CMV enhancer, SV40 enhancer, EF1a enhancer, major late adenoviral protein enhancer, and the like).

[00297] Exemplary mammalian expression vectors include, but are not limited to, pcDNA3, pcDNA3.1(+ / -), pGL3, Petition 870250084408, dated 09 / 19 / 2025, pp. 168 / 297 157 / 214 pZeoSV2(+ / -), pSecTag2, pDisplay, pEF / myc / cyto, pCMV / myc / cyto, pCR3.1, pSinRep5, DH26S, DHBB, pNMT1, pNMT41, pNMT81, which are available from Invitrogen, pCI which is available from Promega, pMbac, pPbac, pBK-RSV and pBK-CMV which are available from Strategene, pTRES which is available from Clontech and its derivatives.

[00298] In some embodiments, expression vectors containing regulatory elements of eukaryotic viruses, such as retroviruses, are used in the present invention. SV40 vectors include pSVT7 and pMT2. In some embodiments, vectors derived from bovine papillomavirus include pBV-1MTHA, and vectors derived from Epstein-Barr virus include pHEBO and p205. Other exemplary vectors include pMSG, pAV009 / A+, pMTO10 / A+, pMAMneo-5, baculovirus pDSVE, and any other vector that allows protein expression under the direction of the SV-40 initial promoter, SV40 subsequent promoter, metallothionein promoter, murine mammary tumor virus promoter, Rous sarcoma virus promoter, polyhedrin promoter, or other promoters that prove effective for expression in eukaryotic cells.

[00299] In some embodiments, for example, in bacterial systems used to express the polypeptides of the present invention, various expression vectors can be advantageously selected, depending on the intended use for the expressed protein. In some embodiments, vectors are desired that direct the expression of high levels of the protein product, possibly as a fusion with a hydrophobic signal sequence, which directs the expressed product to the periplasm of the bacterium or to the culture medium where the protein product is readily purified. In one embodiment, vectors adaptable to such manipulation include, among others, the pET series of E. coli expression vectors (see Studier et al., Methods in Enzymol. 185:60-89 (1990)). Petition 870250084408, dated 09 / 19 / 2025, pp. 169 / 297 158 / 214

[00300] In some embodiments, yeast expression systems are used to express the polypeptides of the present invention. In one embodiment, various vectors containing constitutive or inducible promoters can be used in yeast, as described in U.S. Patent No. 5,932,447. In another embodiment, vectors are used that promote the integration of foreign DNA sequences into the yeast chromosome.

[00301] In some embodiments, recombinant viral vectors are useful for the in vivo expression of the polypeptides of the present invention, since they offer advantages such as lateral infection and targeting specificity. In one embodiment, lateral infection is inherent to the life cycle of, for example, retroviruses and is the process by which a single infected cell produces many progeny virions that bud off and infect neighboring cells. In one embodiment, the result is that a large area is rapidly infected, most of which was not initially infected by the original viral particles. In one embodiment, viral vectors incapable of lateral spreading are produced. In one embodiment, this characteristic can be useful if the desired goal is to introduce a specific gene into only a localized number of target cells.

[00302] In some embodiments, mammalian cell expression systems are used to express the polypeptides of the invention. The mammalian cells may be, for example, Chinese hamster ovary (CHO) cells or their derivatives, and the vector is a suitable vector for the expression of the polypeptides in CHO cells. In some embodiments, the mammalian cells may be ExpiCHO-S™ cells.

[00303] It should be noted that, in addition to containing the elements necessary for the transcription and translation of the inserted coding sequence (which encodes the polypeptide), the expression construct of the pre Petition 870250084408, dated 09 / 19 / 2025, pp. 170 / 297 159 / 214 The invention may also include sequences designed to optimize the stability, production, purification, yield, or activity of the expressed polypeptide. Manufacturing Methods

[00304] The invention provides methods for producing the anti-5T4 antibodies described herein, comprising: (a) placing a plurality of cells in contact with polynucleotides, polynucleotide systems or vectors encoding the antibody; (b) culturing the plurality of cells under conditions in which the antibody is expressed by at least one cell of the plurality of cells; and (c) purifying the antibody.

[00305] The invention provides methods for producing the anti-5T4 drug-antibody conjugates described herein, comprising: (a) placing a plurality of cells in contact with polynucleotides, polynucleotide systems or vectors encoding the antibody; (b) culturing the plurality of cells under conditions in which the bispecific antibody is expressed by at least one cell of the plurality of cells; (c) purifying the antibody; and (d) conjugating the antibody to a chemotherapeutic agent. In some embodiments, the antibody is bispecific or biparatopic, as described herein.

[00306] The invention provides methods for manufacturing an antibody-drug conjugate described herein, comprising: (a) cultivating a cell comprising a nucleic acid construct encoding the bispecific or biparatopic antibody under conditions leading to expression of the bispecific or biparatopic antibody, (b) recovering the bispecific or biparatopic antibody, and (c) conjugating the bispecific or biparatopic antibody to a chemotherapeutic agent.

[00307] The invention provides methods for manufacturing the antibodies described herein, comprising: (a) cultivating a cell comprising a nucleic acid construct encoding the antibody. Petition 870250084408, dated 09 / 19 / 2025, pp. 171 / 297 160 / 214 under conditions leading to antibody expression, wherein the antibody comprises the following structure: (i) a first antibody that binds specifically to a first 5T4 epitope; (ii) a second antibody that binds specifically to a second 5T4 epitope that is not the same as the first 5T4 epitope; wherein the first antibody is operably linked to the second antibody; and (b) recovery of the bispecific antibody.

[00308] A variety of prokaryotic or eukaryotic cells can be used as host expression systems to express the antibodies of the present invention. In some embodiments, these include, but are not limited to, microorganisms such as bacteria transformed with a recombinant bacteriophage DNA expression vector, plasmid DNA, or cosmid DNA containing the polypeptide coding sequence; yeasts transformed with recombinant yeast expression vectors containing the polypeptide coding sequence.

[00309] In some embodiments, the plurality of cells comprises eukaryotic cells. In some embodiments, the eukaryotic cells are mammalian cells. Mammalian cells suitable for the expression of antibody-drug conjugates include CHO cells, PER.C6 cells, murine NS0 cells, and HEK293 cells. The selection of a suitable cell line will be evident to those skilled in the art.

[00310] In some embodiments, the plurality of cells comprises prokaryotic cells, for example, E. coli cells.

[00311] Several methods can be used to introduce the expression vector encoding the antibody of the present invention into cells. Such methods are generally described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Springs Harbor Laboratory, New York (1989, 1992), and in Ausubel et al., Current Protocols in Molecular Cloning. Petition 870250084408, dated 09 / 19 / 2025, p. 172 / 297 161 / 214 Molecular Biology, John Wiley and Sons, Baltimore, Md. (1989), Chang et al., Somatic Gene Therapy, CRC Press, Ann Arbor, Michigan (1995), Vega et al., Gene Targeting, CRC Press, Ann Arbor, Michigan (1995), Vectors: A Survey of Molecular Cloning Vectors and Their Uses, Butterworths, Boston, Massachusetts (1988) and Gilboa et al. / Biotechniques 4 (6): 504-512, 1986] and include, for example, stable or transient transfection, lipofection, electroporation, and infection with recombinant viral vectors. In addition, see U.S. Patents Nos. 5,464,764 and 5,487,992 for positive-negative selection methods.

[00312] In some embodiments, the contact of the plurality of cells with the polynucleotides or vectors encoding the antibodies of the invention comprises transfection.

[00313] The term transfection means the introduction of a foreign nucleic acid into a cell using recombinant DNA technology. The term transformation means the introduction of a foreign (i.e., extrinsic or extracellular) gene, DNA sequence, or RNA into a host cell, such that the host cell expresses the introduced gene or sequence to produce a desired substance, typically a protein or enzyme encoded by the introduced gene or sequence. The introduced gene or sequence may also be termed a cloned or foreign gene or sequence and may include regulatory or control sequences such as start, stop, promoter, signaling, secretion, or other sequences used by a cell's genetic machinery. The gene or sequence may include non-functional sequences or sequences with no known function. A host cell that receives and expresses the introduced DNA or RNA has been transformed and is a transformant or a clone.The DNA or RNA introduced into a host cell can come from any source, including cells of the same genus or species as the host cell, or cells of a different genus or species. Petition 870250084408, dated 09 / 19 / 2025, pp. 173 / 297 162 / 214 different.

[00314] In some embodiments, the contact of the plurality of cells with the polynucleotides or vectors encoding the antibodies of the invention comprises translation. The term translation means the introduction of a foreign nucleic acid into a cell using a viral vector, such as a lentiviral vector.

[00315] In some embodiments, non-bacterial expression systems are used (e.g., mammalian expression systems such as CHO cells) to express the antibody polypeptides. In some embodiments, the expression vector comprises a CMV promoter and a neomycin resistance gene. In alternative embodiments, the expression vector comprises a glutamine synthetase (GS) marker under the control of an SV40 promoter.

[00316] In some modalities, the introduction of nucleic acid by viral infection offers several advantages over other methods, such as lipofection and electroporation, since greater transfection efficiency can be obtained due to the infectious nature of viruses.

[00317] In some embodiments, the transformed cells are cultured under effective conditions that allow the expression of high amounts of antibody or polypeptide. In some embodiments, effective culture conditions include, among others, an effective medium, bioreactor, temperature, pH, and oxygen conditions that allow protein production. A medium typically includes an aqueous solution containing assimilable sources of carbon, nitrogen, and phosphate, and appropriate salts, minerals, metals, and other nutrients, such as vitamins. The cells of the present invention can be cultured in conventional fermentation bioreactors, shake flasks, test tubes, microtiter plates, and Petri dishes. In some embodiments, the culture is carried out at a temperature, pH, and oxygen content appropriate for a recombinant cell. The culture conditions Petition 870250084408, dated 09 / 19 / 2025, pp. 174 / 297 163 / 214 are within the competence of a technician in the subject matter.

[00318] For example, appropriate media for the culture of eukaryotic cells include, but are not limited to, Iscove Modified Dulbecco Medium, RPMI 1640, Minimum Essential Medium-alpha (MEM-alpha), Dulbecco Modified Eagle Medium (DMEM), Grace's Complete Insect Medium, Ham's F-10 or F-12 Medium with L-Glutamine, Schneider's Insect Medium, or any other medium known to one skilled in the art. In addition, the culture media described herein include, but are not limited to, chemically defined media, hydrolysate-containing media, and simple media. The choice of appropriate media and cell culture conditions for a specific cell type will be evident to one skilled in the art.

[00319] In some embodiments, depending on the vector and host system used for production, the polypeptides resulting from the present invention remain within the recombinant cell, secreted into the fermentation medium, secreted into a space between two cell membranes, such as in the periplasmic space in E. coli; or retained on the outer surface of a cell or viral membrane.

[00320] In some embodiments, after a predetermined time in culture, the antibody or polypeptide is recovered.

[00321] The polypeptides of the present invention are purified using a variety of standard protein purification techniques, such as, but not limited to, affinity chromatography, ion-exchange chromatography, filtration, electrophoresis, hydrophobic interaction chromatography, gel filtration chromatography, reverse-phase chromatography, concanavalin A chromatography, chromatofocusing, and differential solubilization.

[00322] In some embodiments, to facilitate retrieval, the expressed coding sequence may be designed to encode the polypeptide of the present invention and the fused cleavable portion. By Petition 870250084408, dated 09 / 19 / 2025, pp. 175 / 297 164 / 214 For example, a polypeptide can be designed so that it can be easily isolated by affinity chromatography; for example, by immobilization on a column specific to the cleavable portion. In one embodiment, a cleavage site is designed between the polypeptide and the cleavable portion, and the polypeptide can be released from the chromatographic column by treatment with an appropriate enzyme or agent that specifically cleaves the polypeptide at this site [e.g., see Booth et al., Immunol. Lett. 19:65-70 (1988); and Gardella et al., J. Biol. Chem. 265:15854-15859 (1990)].

[00323] In some embodiments, the polypeptide of the present invention is recovered in substantially pure form. The term substantially pure refers to a purity that allows the effective use of the protein in the applications described herein.

[00324] In some embodiments, the polypeptides of the present invention can also be synthesized using in vitro expression systems. In one embodiment, the in vitro synthesis methods are well known in the art and the system components are commercially available.

[00325] In some embodiments, polypeptides are synthesized and purified; and their therapeutic efficacy is evaluated in vivo or in vitro. Pharmaceutical Compositions

[00326] The invention provides pharmaceutical compositions comprising anti-5T4 antigen-binding domains, bispecific or biparatopic antibody-drug conjugates described herein, and a pharmaceutically acceptable carrier, diluent or excipient. Pharmaceutical compositions comprising immune cells comprising CARs comprising the antigen-binding domains described herein are also contemplated as being included within the scope of the present invention. Petition 870250084408, dated 09 / 19 / 2025, pp. 176 / 297 165 / 214

[00327] As used herein, pharmaceutical vehicle includes any and all solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic agents and absorption retardants and the like that are physiologically compatible. The carrier materials are non-toxic and do not interfere with the efficacy of the biological activity of the active ingredients. Such preparations may routinely contain salts, buffering agents, preservatives, compatible vehicles and, optionally, other therapeutic agents. Such pharmaceutically acceptable preparations may also routinely contain compatible solid or liquid fillers, diluents or encapsulating substances that are suitable for administration to humans. The term vehicle denotes an organic or inorganic, natural or synthetic ingredient with which the active ingredient is combined to facilitate application.Preferably, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal, or epidermal administration (e.g., by injection or infusion).

[00328] Pharmaceutically acceptable diluents include saline solutions and aqueous buffers. Pharmaceutical carriers include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. The use of such media and agents for pharmaceutically active substances is known in the art.

[00329] The pharmaceutical compositions may be present in a form known in the art and acceptable for therapeutic uses. In some embodiments, the pharmaceutical compositions of the invention are liquid formulations. In other embodiments, the pharmaceutical compositions of the invention are lyophilized. In other embodiments, the pharmaceutical compositions of the invention are reconstituted liquid formulations. In some embodiments, a liquid formulation of the invention is an aqueous formulation. In other embodiments, the formulation Petition 870250084408, dated 09 / 19 / 2025, pp. 177 / 297 166 / 214 liquid lation is not aqueous.

[00330] The compositions comprising the anti-5T4 antigen-binding domains, antibodies, and bispecific antibody-drug conjugates of the present invention can be formulated for administration by a variety of methods known in the art. As will be understood by one skilled in the art, the route and / or mode of administration will vary depending on the desired results. To administer a composition of the invention by certain routes of administration, it may be necessary to co-administer the composition with a material to prevent its inactivation. For example, the antibody-drug conjugate can be administered to an individual in an appropriate carrier, for example, liposomes or a diluent.

[00331] In some embodiments, preparations for administration to individuals include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Some embodiments include non-aqueous solvents such as propylene glycol, polyethylene glycol, vegetable oils (e.g., olive oil), organic esters (e.g., ethyl oleate), and other solvents known to those skilled in the art. Physiologically acceptable carriers (or excipients) are optionally used in certain embodiments of the invention. Examples of these include, for example, saline solution, PBS, Ringer's solution, Ringer's lactate solution, etc. In addition, preservatives and additives are optionally added to the compositions to help ensure stability and sterility. For example, antibiotics and other bactericides, antioxidants, chelating agents, and the like are all optionally present in various embodiments of the compositions described herein.

[00332] Regardless of the route of administration selected, the compositions of the present invention, which may be used in a suitable hydrated form, and / or the pharmaceutical compositions of the present invention, are formulated in pharmaceutical dosage forms. Petition 870250084408, dated 09 / 19 / 2025, pp. 178 / 297 167 / 214 ceutically acceptable by conventional methods known to those skilled in the art.

[00333] The pharmaceutical compositions are optionally administered to individuals requiring treatment (therapeutic or prophylactic) in any appropriate sterile pharmaceutical vehicle. Such a pharmaceutical vehicle acts to maintain the solubility and action of the anti-5T4 antibody or the antibody-drug conjugate.

[00334] In some embodiments, the compositions for use in the methods described herein comprise solutions or emulsions, which in some embodiments are aqueous solutions or emulsions comprising a safe and effective amount of the compounds described herein and, optionally, other compounds, intended for various routes of administration.

[00335] The composition must be sterile and fluid so that it can be administered by syringe. In addition to water, the vehicle is preferably an isotonic buffered saline solution. Adequate fluidity can be maintained, for example, by the use of a coating such as lecithin, by maintaining the necessary particle size in the case of dispersion, and by the use of surfactants. In many cases, it is preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol or sorbitol, and sodium chloride in the composition.

[00336] The actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention may be varied in order to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a specific individual, composition, and route of administration, without being toxic to the individual. The selected dosage will depend on a variety of pharmacokinetic factors, including the activity of the specific compositions of the present invention employed, the route of administration, the time of administration, and the excretion rate of the specific compound. Petition 870250084408, dated 09 / 19 / 2025, pp. 179 / 297 168 / 214 employed, the duration of treatment, other drugs, compounds and / or materials used in combination with the specific compositions employed, the age, sex, weight, condition, general health and previous medical history of the individual to be treated, as well as similar factors well known in the medical field. Therapeutic Methods

[00337] The present invention provides methods for treating a disease or disorder in an individual in need, the method comprising administering a therapeutically effective amount of the bispecific anti-5T4 antibody-drug conjugates or pharmaceutical compositions comprising the bispecific antibody-drug conjugates described herein. Methods comprising administering the anti-5T4 antigen-binding domains, for example, as part of immunotherapy, are also contemplated as being included within the scope of the present invention. The methods of the invention also include adoptive cell therapies comprising administering immune cells, for example, T cells or NK cells, expressing receptors comprising the 5T4 antigen-binding domains described herein.

[00338] In some modalities, the disease or disorder is cancer. In some modalities, cancer comprises a solid tumor.

[00339] In some modalities, the cancer comprises a solid tumor. In some modalities, the cancer is selected from the group consisting of melanoma, renal cell carcinoma, mesothelioma, small cell lung cancer, uveal melanoma, bladder cancer, gastric cancer, squamous cell carcinoma of the head and neck, cutaneous carcinoma, non-small cell lung cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial carcinoma, breast cancer, pancreatic cancer, urothelial cancer, esophageal cancer, hepatocellular carcinoma Petition 870250084408, dated 09 / 19 / 2025, pp. 180 / 297 169 / 214 lar, glioblastoma, glioma or sarcoma.

[00340] In some modalities, the cancer is selected from the group consisting of adrenocortical carcinoma, AIDS-related cancers, AIDS-related lymphoma, anal cancer, anorectal cancer, anal canal cancer, appendix cancer, infantile cerebellar astrocytoma, infantile cerebral astrocytoma, basal cell carcinoma, skin cancer (non-melanoma), biliary cancer, extrahepatic bile duct cancer, intrahepatic bile duct cancer, bladder cancer, urinary bladder cancer, bone and joint cancer, osteosarcoma and malignant fibrous histiocytoma, brain cancer, brain tumor, brainstem glioma, cerebellar astrocytoma, cerebral astrocytoma / malignant glioma, ependymoma, medulloblastoma, supratentorial primitive neuroectodermal tumors, visual and hypothalamic pathway glioma, breast cancer, bronchial adenomas / carcinoids, carcinoid tumor, gastrointestinal, nervous system cancer, lymphoma of the nervous system nervous system, cancer of the central nervous system,Central nervous system lymphoma, cervical cancer, childhood cancers, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disorders, colon cancer, colorectal cancer, cutaneous T-cell lymphoma, lymphoid neoplasm, mycosis fungoides, Seziary syndrome, endometrial cancer, esophageal cancer, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic bile duct cancer, eye cancer, intraocular melanoma, retinoblastoma, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), germ cell tumor, ovarian germ cell tumor, gestational trophoblastic tumor glioma, head and neck cancer, hepatocellular (liver) cancer, Hodgkin's lymphoma, hypopharyngeal cancer, intraocular melanoma, eye cancer, islet cell tumors (pancreas) endocrine), Kaposi's sarcoma, renal cancer, renal cancer,kidney cancer, cancer, Petition 870250084408, dated 09 / 19 / 2025, pp. 181 / 297 170 / 214 laryngeal, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, hairy cell leukemia, lip and oral cavity cancer, liver cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, AIDS-related lymphoma, non-Hodgkin lymphoma, primary central nervous system lymphoma, Waldenstrom's macroglobulinemia, medulloblastoma, melanoma, intraocular (ocular) melanoma, Merkel cell carcinoma, malignant mesothelioma, mesothelioma, metastatic squamous neck cancer, mouth cancer, tongue cancer, multiple endocrine neoplasia syndrome, mycosis fungoides, myelodysplastic syndromes, myelodysplastic / myeloproliferative diseases, chronic myeloid leukemia, acute myeloid leukemia, multiple myeloma, chronic myeloproliferative disorders, cancer nasopharyngeal, neuroblastoma, oral cancer, oral cavity cancer, oropharyngeal cancer, ovarian cancerOvarian epithelial cancer, low malignant ovarian tumor, pancreatic cancer, pancreatic islet cell carcinoma, paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineoblastoma and supratentorial primitive neuroectodermal tumors, pituitary tumor, plasma cell neoplasm / multiple myeloma, pleuropulmonary blastoma, prostate cancer, rectal cancer, renal pelvis and ureter cancer, transitional cell carcinoma, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, Ewing family sarcoma tumors, Kaposi's sarcoma, soft tissue sarcoma, epithelioid sarcoma, synovial sarcoma, uterine cancer, uterine sarcoma, skin cancer (non-melanoma), skin cancer (melanoma), Merkel cell skin carcinoma, small bowel cancer, sarcoma of soft tissue cancer, squamous cell carcinoma, stomach (gastric) cancer, supratentorial primitive neuroectodermal tumors,testicular cancer, throat cancer, thymoma, thymoma and, Petition 870250084408, dated 09 / 19 / 2025, pp. 182 / 297 171 / 214 thymic carcinoma, thyroid cancer, transitional cell carcinoma of the renal pelvis and ureter and other urinary organs, gestational trophoblastic tumor, urethral cancer, endometrial uterine cancer, uterine sarcoma, uterine body cancer, vaginal cancer, vulvar cancer and Wilms' tumor.

[00341] A cancer treated with antigen-binding domains, antibodies, immune cells, or antibody-drug conjugates or pharmaceutical compositions of the invention comprising the same, may be staged according to a classification of the American Joint Committee on Cancer (AJCC) as Stage I, Stage IIA, Stage IIB, Stage IIIA, Stage IIIB, Stage IIIC, or Stage IV. A cancer requiring treatment may be graded according to an AJCC classification such as Grade GX (e.g., grade cannot be assessed), Grade 1, Grade 2, Grade 3, or Grade 4. A cancer requiring treatment may be staged according to an AJCC pathological classification (pN) of pNX, pN0, PN0 (I-), PN0 (I+), PN0 (mol-), PN0 (mol+), PN1, PN1 (mi), PN1a, PN1b, PN1c, pN2, pN2a, pN2b, pN3, pN3a, pN3b, or pN3c. Alternatively, or additionally, a cancer may be staged according to the TNM staging system, which divides most cancer types into 4 stages.Stage 1 generally means that a cancer is relatively small and contained within the organ of origin. Stage 2 cancers have generally not begun to spread to surrounding tissues, but the tumor is larger than a Stage 1 tumor. In some modalities, Stage 2 means that the cancer has spread to lymph nodes near the tumor. Stage 3 cancers are generally larger and have begun to spread to surrounding tissues and lymph nodes. Stage 4, or metastatic, cancers are typically cancers that have spread from the point of origin to other organ(s) in the body.

[00342] As used herein, a normal cell is a cell that Petition 870250084408, dated 09 / 19 / 2025, pp. 183 / 297 172 / 214 cannot be classified as part of a proliferative cell disorder. A normal cell does not exhibit unregulated or abnormal growth, or both, that could lead to the development of an undesirable condition or disease. Preferably, a normal cell has cell cycle checkpoint control mechanisms that function normally.

[00343] As used herein, contact with a cell refers to a condition in which an antibody-drug conjugate or other composition of matter is in direct contact with a cell, or is close enough to induce a desired biological effect in a cell.

[00344] As used herein, monotherapy refers to the administration of a single active or therapeutic compound to an individual who needs it. Preferably, monotherapy will involve the administration of a therapeutically effective amount of an active compound. Monotherapy may be contrasted with combination therapy, in which a combination of multiple active compounds is administered, preferably with each component of the combination present in a therapeutically effective amount.

[00345] As used herein, treating or treating describes the management and care of an individual for the purpose of combating a disease, condition or disorder and includes the administration of an anti-5T4 antigen-binding domain, antibody, antibody-drug conjugate, immune cell expressing an anti-5T4 receptor or pharmaceutical composition of the invention comprising the same, to alleviate the symptoms or complications of cancer or to eliminate cancer.

[00346] As used herein, the term alleviate describes a process by which the severity of a sign or symptom of cancer is reduced. It is important to note that a sign or symptom can be alleviated without being eliminated. In a preferred modality, the administration of Petition 870250084408, dated 09 / 19 / 2025, pp. 184 / 297 173 / 214 A recombinant anti-5T4 antibody drug conjugate or pharmaceutical compositions of the invention leads to the elimination of a sign or symptom; however, elimination is not required. Effective dosages are expected to decrease the severity of a sign or symptom. For example, a sign or symptom of a disease such as cancer, which may occur in multiple locations, is alleviated if the severity of the cancer is reduced in at least one of the multiple locations.

[00347] As used herein, the term severity describes the potential of cancer to transform from a precancerous, or benign, state into a malignant state. Alternatively, or additionally, severity describes the stage of the cancer, for example, according to the TNM system (accepted by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC)) or by other methods recognized by the art. Cancer stage refers to the extent or severity of the cancer, based on factors such as the location of the primary tumor, the size of the tumor, the number of tumors, and lymph node involvement (spread of cancer to the lymph nodes). Alternatively, or additionally, severity describes the grade of the tumor by methods recognized by the art (see the National Cancer Institute, www.cancer.gov).Tumor grading is a system used to classify cancer cells in terms of how abnormal they appear under a microscope and how quickly the tumor is likely to grow and spread. Many factors are considered when determining tumor grade, including the structure and growth pattern of the cells. The specific factors used to determine tumor grade vary depending on the type of cancer. Severity also describes a histological grade, also called differentiation, which refers to how closely the tumor cells resemble normal cells of the same tissue type (see the National Cancer Institute, www.cancer.gov). Furthermore, a. Petition 870250084408, dated 09 / 19 / 2025, pp. 185 / 297 174 / 214 severity describes a nuclear grade, which refers to the size and shape of the nucleus in tumor cells and the percentage of tumor cells that are dividing (see the National Cancer Institute, www.cancer.gov).

[00348] As used herein, the term aggressive indicates a cancer that can grow, form, or spread rapidly. Cancers termed aggressive may be amenable to treatment or may be resistant to treatment. An aggressive cancer may encompass any type of cancer. Alternatively, or additionally, the term aggressive may describe a cancer that requires more severe or intensive treatment than usual.

[00349] As used herein, the term refractory describes a cancer that does not respond to an attempt at treatment. Refractory cancers may also be referred to as resistant cancers.

[00350] In another aspect of the invention, severity describes the degree to which a tumor has secreted growth factors, degraded the extracellular matrix, become vascularized, lost adhesion to adjacent tissues, or metastasized. Furthermore, severity describes the number of sites to which a primary tumor has metastasized. Finally, severity includes the difficulty of treating tumors of various types and locations. For example, inoperable tumors, those cancers that have greater access to multiple body systems (hematologic and immunological tumors), and those that are more resistant to traditional treatments are considered the most severe. In these situations, prolonging the individual's life expectancy and / or reducing pain, decreasing the proportion of cancerous cells or restricting the cells to one system, and improving the tumor stage / grade / histologic grade / nuclear grade of the cancer are considered as relief of a sign or symptom of cancer.

[00351] As used herein, the term symptom is defined as a Petition 870250084408, dated 09 / 19 / 2025, pp. 186 / 297 175 / 214 indication of illness, disease, injury, or that something is not right in the body. The symptoms are felt or perceived by the individual who presents them, but may not be easily perceived by others. Others are defined as professionals who are not in the health field.

[00352] As used here, the term sign is also defined as an indication that something is not right in the body. But signs are defined as things that can be seen by a doctor, nurse, or other health professional.

[00353] Cancer is a group of diseases that can cause any sign or symptom. The signs and symptoms will depend on the location of the cancer, the size of the cancer, and how much it affects nearby organs or structures. If a cancer spreads (metastasis), symptoms may appear in different parts of the body.

[00354] As cancer grows, it begins to press on nearby organs, blood vessels, and nerves. This pressure creates some of the signs and symptoms of cancer. Cancers can form in locations where they don't cause any symptoms until the cancer has grown quite large.

[00355] Cancer can also cause symptoms such as fever, fatigue, or weight loss. This can occur because cancer cells consume a large portion of the body's energy supply or release substances that alter the body's metabolism. Or cancer can cause the immune system to react in ways that produce these symptoms. Although the signs and symptoms listed above are the most common observed in cancer, there are many others that are less common and are not listed here. However, all signs and symptoms of cancer recognized by the art are contemplated and covered by the invention.

[00356] Cancer treatment can result in a reduction in size Petition 870250084408, dated 09 / 19 / 2025, pp. 187 / 297 176 / 214 tumor size. The reduction in the size of a tumor may also be called tumor regression. Preferably, after treatment according to the methods of the invention, the size of the tumor is reduced by 5% or more compared to its pre-treatment size; more preferably, the size of the tumor is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and most preferably, reduced by more than 75% or more. The size of a tumor can be measured by any reproducible measuring means. The size of a tumor can be measured as a tumor diameter.

[00357] Cancer treatment can result in a reduction in tumor volume. Preferably, after treatment according to the methods of the invention, the tumor volume is reduced by 5% or more relative to its pre-treatment size; more preferably, the tumor volume is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and most preferably, reduced by more than 75%. The tumor volume can be measured by any reproducible measuring means.

[00358] Cancer treatment can result in a decrease in the number of tumors. Preferably, after treatment, the number of tumors is reduced by 5% or more compared to the number before treatment; more preferably, the number of tumors is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and most preferably, reduced by more than 75%. The Petition 870250084408, dated 09 / 19 / 2025, pp. 188 / 297 177 / 214 The number of tumors can be measured by any reproducible measuring method. The number of tumors can be measured by counting tumors visible to the naked eye or with specific magnification. Preferably, the specific magnification is 2x, 3x, 4x, 5x, 10x or 50x.

[00359] Cancer treatment can result in a decrease in the number of metastatic lesions in other tissues or organs distant from the primary tumor site. Preferably, after treatment according to the methods of the invention, the number of metastatic lesions is reduced by 5% or more compared to the number prior to treatment; more preferably, the number of metastatic lesions is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and most preferably, reduced by more than 75%. The number of metastatic lesions can be measured by any reproducible measuring means. The number of metastatic lesions can be measured by counting metastatic lesions visible to the naked eye or with a specific magnification. Preferably, the specific magnification is 2x, 3x, 4x, 5x, 10x or 50x.

[00360] Cancer treatment may result in an increase in the average survival time of a population of treated individuals compared to a population not receiving the anti-5T4 drug-antibody conjugate, or pharmaceutical composition of the invention containing it. Preferably, the average survival time is increased by more than 30 days; more preferably, by more than 60 days; most preferably, by more than 90 days; and even more preferably, by more than 120 days. An increase in the average survival time of a population can be measured by any reproducible means. An increase in the average survival time of a population can be measured, for example, by calculating Petition 870250084408, dated 09 / 19 / 2025, pp. 189 / 297 178 / 214 for a population the average duration of survival after the start of treatment with an active compound. An increase in the average survival time of a population can also be measured, for example, by calculating for a population the average duration of survival after the completion of a first cycle of treatment with an active compound.

[00361] Cancer treatment may result in a decrease in the mortality rate of a population of treated individuals compared to a population not receiving the anti-5T4 drug-antibody conjugate, or pharmaceutical composition of the invention containing it. Cancer treatment may result in a decrease in the mortality rate of a population of treated individuals compared to an untreated population. Cancer treatment may result in a decrease in the mortality rate of a population of treated individuals compared to a population receiving monotherapy with a drug other than an anti-5T4 drug-antibody conjugate or pharmaceutical composition of the invention. A decrease in the mortality rate of a population of treated individuals may be measured by any reproducible means.A decrease in the mortality rate of a population can be measured, for example, by calculating, for a population, the average number of disease-related deaths per unit of time after the start of treatment with an active compound. A decrease in the mortality rate of a population can also be measured, for example, by calculating, for a population, the average number of disease-related deaths per unit of time after the completion of a first cycle of treatment with the antibody-drug conjugates described herein.

[00362] Cancer treatment can result in a decrease in the rate of tumor growth. Preferably, after treatment, the Petition 870250084408, dated 09 / 19 / 2025, pp. 190 / 297 179 / 214 The tumor growth rate is reduced by at least 5% compared to the pre-treatment number; more preferably, the tumor growth rate is reduced by at least 10%; more preferably, reduced by at least 20%; more preferably, reduced by at least 30%; more preferably, reduced by at least 40%; more preferably, reduced by at least 50%; even more preferably, reduced by at least 50%; and most preferably, reduced by at least 75%. The tumor growth rate can be measured by any reproducible measurement method. The tumor growth rate can be measured according to a change in tumor diameter per unit of time.

[00363] Cancer treatment can result in a decrease in tumor regrowth. Preferably, after treatment, tumor regrowth is less than 5%; more preferably, tumor regrowth is less than 10%; more preferably, less than 20%; more preferably, less than 30%; more preferably, less than 40%; more preferably, less than 50%; even more preferably, less than 50%; and most preferably, less than 75%. Tumor regrowth can be measured by any reproducible measurement method. Tumor regrowth is measured, for example, by measuring an increase in the diameter of a tumor after a previous tumor reduction that followed treatment. A decrease in tumor regrowth is indicated by the failure of tumors to r...

Claims

1. Antibody-drug conjugate, characterized in that it comprises: a. a first antigen-binding domain that binds specifically to a first 5T4 epitope; b. a second antigen-binding domain that binds specifically to a second 5T4 epitope that is not the same as the first 5T4 epitope; and c. a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain.

2. Antibody-drug conjugate according to claim 1, characterized in that the first and second antigen-binding domains are independently selected from the group consisting of a Fab fragment, an F(ab')2 fragment, an scFv, a scab, a dAb, a single-domain heavy chain antibody and a single-domain light chain antibody.

3. Antibody-drug conjugate according to claim 1, characterized in that it comprises a full-size IgG antibody comprising the first antigen-binding domain.

4. Antibody-drug conjugate according to any one of claims 1 to 3, characterized in that the second antigen-binding domain comprises a scFv.

5. Antibody-drug conjugate according to any one of claims 1 to 4, characterized in that the full-size IgG antigen-binding domain comprises two heavy chains and two light chains.

6. Antibody-drug conjugate according to any one of claims 1 to 5, characterized in that Petition 870250084408, dated 09 / 19 / 2025, p. 227 / 297 2 / 35 second antigen-binding domain comprises a scFv, and in that the antibody-drug conjugate comprises two second scFv antigen-binding domains that both specifically bind to the second 5T4 epitope.

7. Antibody-drug conjugate according to any one of claims 2 to 6, characterized in that the scFv comprises a heavy chain and a light chain, and wherein: (a) the C-terminus of the light chain are operably linked to the N-terminus of the heavy chain by means of a linker, or (b) the C-terminus of the heavy chain are operably linked to the N-terminus of the light chain by means of a linker.

8. Antibody-drug conjugate according to claim 7, characterized in that the ligand comprises a sequence with SEQ ID NO:

153.

9. Antibody-drug conjugate according to any one of claims 6 to 8, characterized in that the N-terminus of the second antigen-binding domain are operably linked to the C-terminus of a full-size IgG antibody heavy chain comprising the first antigen-binding domain.

10. Antibody-drug conjugate according to any one of claims 6 to 8, characterized in that the C-terminus of the second antigen-binding domain are operably linked to the N-terminus of a full-size IgG antibody heavy chain.

11. Antibody-drug conjugate according to claim 9 or 10, characterized in that the second antigen-binding domain is operably linked to the full-size IgG antibody heavy chain using a linker.

12. Antibody-drug conjugate according to which Petition 870250084408, dated 09 / 19 / 2025, pp. 228 / 297 3 / 35, one of claims 9 to 11, characterized in that the ligand comprises or consists of an amino acid sequence of SEQ ID NO:

152.

13. Antibody-drug conjugate according to any one of claims 5 to 12, characterized in that the full-size IgG antibody heavy chains comprise a variable region heavy chain domain and a constant region heavy chain domain.

14. Antibody-drug conjugate according to claim 13, characterized in that the heavy chain constant region domain is an IgG1 isotype constant region domain.

15. Antibody-drug conjugate according to any one of claims 5 to 14, characterized in that the full-size IgG antibody light chains comprise a variable region light chain domain and a constant region light chain domain.

16. Antibody-drug conjugate according to claim 15, characterized in that the constant region domain of the light chain is a constant region domain of the IgG1 isotype.

17. Antibody-drug conjugate according to any one of claims 13 to 16, characterized in that the heavy chain constant region domain comprises at least one mutation that reduces effector function, prolongs half-life, or a combination thereof.

18. Antibody-drug conjugate according to claim 17, characterized in that at least one mutation comprises an F at position 237 with respect to SEQ ID NO: 100 (L234F), a C or A at position 242 with respect to SEQ ID NO: 100 Petition 870250084408, dated 09 / 19 / 2025, pp. 229 / 297 4 / 35 (S239C / A), an A at position 437 with respect to SEQ ID NO: 100 (N434A), or a combination thereof.

19. Antibody-drug conjugate according to claim 17, characterized in that at least one mutation comprises an F at position 237 with respect to SEQ ID NO: 100 (L234F), a C or A at position 242 with respect to SEQ ID NO: 100 (S239C / A), and an A at position 437 with respect to SEQ ID NO: 100 (N434A).

20. Antibody-drug conjugate according to any one of claims 1 to 19, characterized in that it comprises a full-size IgG antibody comprising the first antigen-binding domain, and wherein the second antigen-binding domain comprises an scFv, and the antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising, from the N to C termini, the full-size IgG antibody heavy chain, a linker, and the second antigen-binding domain; and (b) two polypeptides comprising the full-size IgG antibody light chain.

21. Antibody-drug conjugate according to any one of claims 1 to 19, characterized in that it comprises a full-size IgG antibody comprising the first antigen-binding domain, and wherein the second antigen-binding domain comprises a scFv, and the antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising, from the N to C termini, the second antigen-binding domain, a linker, and the full-size IgG antibody; and (b) two polypeptides comprising the full-size IgG antibody light chain. Petition 870250084408, dated 09 / 19 / 2025, pp. 230 / 297 5 / 35 22. Antibody-drug conjugate according to claim 20 or 21, characterized in that the ligand comprises an amino acid sequence of SEQ ID NO:

152.

23. Antibody-drug conjugate according to any one of claims 1 to 22, characterized in that both the first and second antigen-binding domains comprise: a. a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4, and 13 to 23; b. an HC CDR2 sequence selected from the group consisting of SEQ ID NOs: 2, 5, and 24 to 26 and 28 to 39; and c. an HC CDR3 sequence selected from the group consisting of SEQ ID NOs: 3, 6, and 40 to 52; and wherein one or more of the CDR1, CDR2, and CDR3 sequences are not the same between the first and second antigen-binding domains.

24. Antibody-drug conjugate according to any one of claims 1 to 23, characterized in that both the first and second antigen-binding domains comprise: a. a complementarity-determining region (CDR1) sequence of light chain (LC) selected from the group consisting of SEQ ID NOs: 7, 10, and 53 to 66; b. a CDR2 sequence of LC selected from the group consisting of SEQ ID NOs: 8, 11, and 67 to 75; c. a CDR3 sequence of LC selected from the group consisting of SEQ ID NOs: 9, 12, and 76 to 83; and wherein one or more of the CDR1, CDR2, and CDR3 sequences are not the same between the first and second antigen-binding domains. 231 / 297 6 / 35 antigen.

25. Antibody-drug conjugate according to any one of claims 1 to 24, characterized in that the first antigen-binding domain comprises a variable region heavy chain domain comprising: a. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; b. a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 2, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; c. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 3, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; and wherein the first antigen-binding domain comprises a variable region light chain domain comprising: a.a. a CDR1 LC sequence comprising an amino acid sequence of SEQ ID NO: 7 or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it; b. a CDR2 LC sequence comprising an amino acid sequence of SEQ ID NO: 8 or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it; and c. a CDR3 LC sequence comprising an amino acid sequence of SEQ ID NO: 9 or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it.

26. Antibody-drug conjugate according to any one of claims 1 to 25, characterized in that the second antigen-binding domain comprises a variable region heavy chain domain comprising: a. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 4, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; b. a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; c. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6, or a sequence having 1, 2 or 3 substitutions, insertions or deletions relative thereto; and wherein the second antigen-binding domain comprises a variable region light chain domain comprising: a.a. a CDR1 LC sequence comprising an amino acid sequence of SEQ ID NO: 10, or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it; b. a CDR2 LC sequence comprising an amino acid sequence of SEQ ID NO: 11, or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it; and c. a CDR3 LC sequence comprising an amino acid sequence of SEQ ID NO: 12, or a sequence having 1, 2 or 3 substitutions, insertions or deletions in relation to it.

27. Antibody-drug conjugate according to any one of claims 1 to 26, characterized in that the first and / or second antigen-binding domain comprises a variable region heavy chain domain comprising a sequence selected from the group consisting of SEQ ID NOs: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 168, 170 and 172, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with the same; and in which the first and / or second domain of connection to the Petition 870250084408, of 19 / 09 / 2025, page.233 / 297 8 / 35 tigen comprise a variable light chain region domain comprising a sequence selected from the group consisting of SEQ ID NOs: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

28. Antibody-drug conjugate according to any one of claims 1 to 27, characterized in that the first and / or second antigen-binding domain comprises a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96 or 97, and a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98 or 99.

29. Antibody-drug conjugate according to any one of claims 1 to 28, characterized in that: the first antigen-binding domain comprises a. a variable region heavy chain domain comprising an amino acid sequence of SEQ ID NO: 96, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and b. a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 98, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and wherein the second antigen-binding domain comprises: a. a variable region heavy chain domain comprising an amino acid sequence of SEQ ID 97, or a Petition 870250084408, dated 09 / 19 / 2025, p.234 / 297 9 / 35 sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with the same; and b. a variable region light chain domain comprising an amino acid sequence of SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with the same.

30. Antibody-drug conjugate according to any one of claims 1 to 29, characterized in that it comprises a full-size IgG antibody comprising the first antigen-binding domain, and wherein the antibody-drug conjugate comprises: two polypeptides comprising a first antigen-binding domain heavy chain variable region comprising a sequence of SEQ ID NO: 96, a first linker comprising a sequence of SEQ ID NO: 152, a second antigen-binding domain heavy chain variable region comprising a sequence of SEQ ID NO: 97, a second linker comprising a sequence of SEQ ID NO: 153, and a second antigen-binding domain light chain variable region comprising a sequence of SEQ ID NO:

99.

31. Antibody-drug conjugate according to claim 30, characterized in that it comprises two polypeptides comprising a second variable region light chain domain of antigen-binding domain comprising a sequence of SEQ ID NO:

98.

32. Antibody-drug conjugate according to claim 31, characterized in that the IgG antibody of natural size comprises a constant region domain of the IgG1 isotype.

33. Antibody-drug conjugate according to any one of claims 1 to 32, characterized in that the second antigen-binding domain is an scFv comprising a heavy chain domain comprising a sequence with SEQ ID NO: 97, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and a variable region light chain domain comprising a sequence with SEQ ID NO: 99, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

34. Antibody-drug conjugate according to any one of claims 1 to 33, characterized in that it comprises a full-size IgG antibody comprising the first antigen-binding domain, and wherein the second antigen-binding domain comprises an scFv, and the antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising, from the N to C termini, a first antigen-binding domain heavy chain variable region domain comprising a sequence of SEQ ID NO: 96, an IgG1 isotype constant region domain comprising a sequence of SEQ ID NO: 148, a first linker comprising a sequence of SEQ ID NO: 152, a second antigen-binding domain heavy chain variable region domain comprising a sequence of SEQ ID NO: 97, a second linker comprising a sequence of SEQ ID NO: 153,and a second variable light chain region of antigen-binding domain comprising a sequence of SEQ ID NO: 99; (b) two polypeptides comprising, from the N to C termini, a first variable light chain domain of antigen-binding domain comprising a sequence of SEQ ID NO: 98, and a constant region light chain domain comprising a sequence of SEQ ID NO:

149.

35. Antibody-drug conjugate according to any one of claims 1 to 34, characterized in that it comprises a full-size IgG antibody comprising the first antigen-binding domain, and wherein the second antigen-binding domain comprises an scFv, and the antibody-drug conjugate comprises four polypeptides comprising: (a) two polypeptides comprising a sequence with SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity thereto; and (b) two polypeptides comprising a sequence with SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity thereto.

36. Antibody-drug conjugate according to any one of claims 1 to 35, characterized in that the chemotherapeutic agent is conjugated to at least one of a full-size IgG antibody comprising the first antigen-binding domain or the second antigen-binding domain via a ligand.

37. Antibody-drug conjugate according to any one of claims 1 to 36, characterized in that the chemotherapeutic agent is an auristatin.

38. Antibody-drug conjugate according to claim 37, characterized in that auristatin is selected from the group consisting of auristatin E (AE), monomethyl auristatin D (MMAD), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), and synthetic analogs of dolastatin.

39. Antibody-drug conjugate according to any one of claims 36 to 38, characterized in that the ligand is a cleavable ligand.

40. Antibody-drug conjugate according to any one of claims 36 to 38, characterized in that the ligand is a non-cleavable ligand.

41. Antibody-drug conjugate according to any one of claims 1 to 40, characterized in that the antibody-drug conjugate is tetravalent for binding to a 5T4 antigen.

42. Antibody-drug conjugate according to any one of claims 1 to 41, characterized in that the equilibrium dissociation constant (KD) for 5T4 binding of at least one of the first antigen-binding domains or the second antigen-binding domain is between 3.63 x 10-12 and 7.75 x 1010 M.

43. Antibody-drug conjugate according to claim 42, characterized in that KD is less than or equal to 7.75 x 10-10 M.

44. Antibody-drug conjugate according to any one of claims 1 to 43, characterized in that the equilibrium dissociation constant (KD) for the 5T4 binding of the first antigen-binding domain is between 3.63 x 10-12 and 1.43 x 10-9 M.

45. Antibody-drug conjugate according to any one of claims 1 to 44, characterized in that the equilibrium dissociation constant (KD) for the 5T4 binding of the second antigen-binding domain is between 3.63 x 10-12 and 1.34 x 10-9 M.

46. ​​Antibody-drug conjugate according to any one of claims 1 to 45, characterized in that the equilibrium dissociation constant (KD) for 5T4 binding of both the first antigen-binding domain and the second antigen-binding domain is between 3.63 x 10-12 and 7.75 x 10-10 M.

47. Antibody-drug conjugate according to any one of claims 1 to 46, characterized in that the equilibrium dissociation constant (KD) for the binding of the Fc gamma IIa receptor to an IgG antibody comprising the first and / or second antigen-binding domains is less than or equal to 3.74 x 10-6 M.

48. Antibody-drug conjugate according to any one of claims 1 to 47, characterized in that the equilibrium dissociation constant (KD) for binding of Fc gamma IIb receptor to an IgG antibody comprising the first and / or second antigen-binding domains is less than or equal to 1.16 x 10-7 M.

49. Antibody-drug conjugate according to any one of claims 1 to 48, characterized in that the equilibrium dissociation constant (KD) for binding of Fc gamma IIIa receptor to an IgG antibody comprising the first and / or second antigen-binding domains is less than or equal to 5.05 x 10-8 M.

50. Nucleic acid system, characterized in that it encodes the bispecific antibody as defined in any one of claims 1 to 49.

51. Vectors, characterized in that they comprise Petition 870250084408, dated 09 / 19 / 2025, page 239 / 297 14 / 35 the nucleic acid system as defined in claim 50.

52. Cell, characterized in that it comprises the nucleic acid system as defined in claim 50 or the vector as defined in claim 51.

53. Pharmaceutical composition, characterized in that it comprises the antibody-drug conjugate as defined in any one of claims 1 to 49, and a pharmaceutically acceptable excipient, diluent or carrier.

54. Method for preparing the antibody-drug conjugate, characterized in that it comprises: a. contacting a plurality of cells with the nucleic acid system as defined in claim 50 or the vector as defined in claim 51; b. culturing the plurality of cells under conditions in which the bispecific antibody is expressed by at least one cell of the plurality of cells; c. purifying the bispecific antibody; and d. conjugating the bispecific antibody to a chemotherapeutic agent.

55. Antibody-drug conjugate according to any one of claims 1 to 49 or the pharmaceutical composition according to claim 53, characterized in that it is for use in a method of treating cancer in an individual.

56. Antibody-drug conjugate according to any one of claims 1 to 49, characterized in that it is for use in the manufacture of a medicament for the treatment of cancer in an individual.

57. A method for treating cancer in an individual, characterized in that it comprises administering a therapeutically effective amount of the antibody-drug conjugate as defined in any of claims 1 to 49.

58. A method for treating cancer in an individual in need thereof, characterized in that it comprises administering to an individual in need thereof a therapeutically effective amount of an antibody-drug conjugate, wherein the antibody-drug conjugate comprises: a. a first antigen-binding domain that binds specifically to a first 5T4 epitope; b. a second antigen-binding domain that binds specifically to a second 5T4 epitope that is not the same as the first 5T4 epitope; and c. a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain.

59. Method according to claim 58, characterized in that the antibody-drug conjugate comprises two polypeptides comprising an amino acid sequence of SEQ ID NO: 100 or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and two polypeptides comprising an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith.

60. Method according to any one of claims 57 to 59, characterized in that the cancer cells express 5T4.

61. Method according to any one of claims 57 to 60, characterized in that the cancer is selected Petition 870250084408, dated 09 / 19 / 2025, pp. 241 / 297 16 / 35 from the group consisting of lung, gastric, ovarian, colorectal, bladder, breast, cervical, mesothelioma, ovarian, pancreatic, prostate and renal cancer.

62. Method according to claim 61, characterized in that the lung cancer is a non-small cell lung cancer.

63. A method according to any one of claims 57 to 62, characterized in that the first antibody and the second antibody bind to different 5T4 molecules on the surface of at least one cancer cell.

64. Method according to any one of claims 57 to 62, characterized in that the first antibody and the second antibody bind to the same 5T4 molecule on the surface of a cancer cell.

65. A method according to any one of claims 57 to 64, characterized in that the method reduces a sign or symptom of cancer.

66. A method according to any one of claims 57 to 65, characterized in that the method reduces tumor volume, the number of tumors, decreases the tumor growth rate, or a combination thereof.

67. A method according to any one of claims 57 to 66, characterized in that the method increases the survival of the individual.

68. Method for manufacturing a bispecific antibody-drug conjugate, characterized in that it comprises: (a) cultivating a cell comprising a nucleic acid system encoding a bispecific antibody under conditions leading to the expression of the bispecific antibody, wherein the bispecific antibody comprises the following structure: Petition 870250084408, dated 19 / 09 / 2025, page 242 / 297 17 / 35 a. a first antigen-binding domain that specifically binds to a first 5T4 epitope; b. a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and c. a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; and (b) recovering the bispecific antibody; and (c) conjugate the bispecific antibody to a chemotherapeutic agent.

69. Kit, characterized in that it comprises the antibody-drug conjugate as defined in any one of claims 1 to 49, the nucleic acid system as defined in claim 50, the vector as defined in claim 51, the cell as defined in claim 52, or the pharmaceutical composition as defined in claim 53, 70. Antigen-binding domain, characterized in that it comprises a heavy chain variable region domain and a light chain variable region domain; wherein the heavy chain variable region domain comprises: a. a heavy chain (HC) complementarity-determining region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 1, 4 and 13 to 23, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; b. a HC CDR2 sequence selected from the group consisting of SEQ ID NOs: 2, 5, and 24 to 39, or a sequence having 1, 2 or 3 substitutions, insertions or deletions thereto; and c. a HC CDR3 sequence selected from the group Petition 870250084408, dated 19 / 09 / 2025, page. 243 / 297 18 / 35 consisting of SEQ ID Nos: 3, 6, and 40 to 52, or a sequence having 1, 2, or 3 substitutions, insertions, or deletions in relation thereto; and wherein the variable region domain of the light string comprises: a.a. a light chain (LC) complementarity determination region (CDR1) sequence selected from the group consisting of SEQ ID NOs: 7, 10, and 53 to 66, or a sequence having 1, 2, or 3 substitutions, insertions, or deletions relative to it; b. a light chain CDR2 sequence selected from the group consisting of SEQ ID NOs: 8, 11, and 67 to 75, or a sequence having 1, 2, or 3 substitutions, insertions, or deletions relative to it; and c. a light chain CDR3 sequence selected from the group consisting of SEQ ID NOs: 9, 12, and 76 to 83, or a sequence having 1, 2, or 3 substitutions, insertions, or deletions relative to it.

71. Antigen-binding domain according to claim 70, characterized in that the variable region heavy chain domain comprises: a. a CDR1 of HC comprising SEQ ID NO: 1, a CDR2 of HC comprising SEQ ID NO: 2, and a CDR3 of HC comprising SEQ ID NO: 3; b. a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 5, and a CDR3 of HC comprising SEQ ID NO: 6; c. a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 24, and a CDR3 of HC comprising SEQ ID NO: 40; d. a CDR1 of HC comprising SEQ ID NO: 13, a CDR2 of HC comprising SEQ ID NO: 25, and a CDR3 of HC Petition 870250084408, dated 09 / 19 / 2025, page 244 / 297 19 / 35 comprising SEQ ID NO: 41; and a CDR1 of HC comprising SEQ ID NO: 14, a CDR2 of HC comprising SEQ ID NO: 26, and a CDR3 of HC comprising SEQ ID NO: 42; f.a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 28, and a CDR3 of HC comprising SEQ ID NO: 43; g. a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 29, and a CDR3 of HC comprising SEQ ID NO: 44; h. a CDR1 of HC comprising SEQ ID NO: 16, a CDR2 of HC comprising SEQ ID NO: 30, and a CDR3 of HC comprising SEQ ID NO: 45; i. a CDR1 of HC comprising SEQ ID NO: 17, a CDR2 of HC comprising SEQ ID NO: 31, and a CDR3 of HC comprising SEQ ID NO: 46; j. a CDR1 of HC comprising SEQ ID NO: 18, a CDR2 of HC comprising SEQ ID NO: 32, and a CDR3 of HC comprising SEQ ID NO: 47; k. a CDR1 of HC comprising SEQ ID NO: 19, a CDR2 of HC comprising SEQ ID NO: 33, and a CDR3 of HC comprising SEQ ID NO: 48; l. a CDR1 of HC comprising SEQ ID NO: 20, a CDR2 of HC comprising SEQ ID NO: 34, and a CDR3 of HC comprising SEQ ID NO: 49; m.a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 35, and a CDR3 of HC comprising SEQ ID NO: 50; n. a CDR1 of HC comprising SEQ ID NO: 14, a CDR2 of HC comprising SEQ ID NO: 36, and a CDR3 of HC Petition 870250084408, dated 09 / 19 / 2025, p. 245 / 297 20 / 35 comprising SEQ ID NO: 51; o. a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 37, and a CDR3 of HC comprising SEQ ID NO: 3; p. a CDR1 of HC comprising SEQ ID NO: 21, a CDR2 of HC comprising SEQ ID NO: 38, and a CDR3 of HC comprising SEQ ID NO: 3; q. a CDR1 of HC comprising SEQ ID NO: 22, a CDR2 of HC comprising SEQ ID NO: 39, and a CDR3 of HC comprising SEQ ID NO: 45; or r. a CDR1 of HC comprising SEQ ID NO: 23, a CDR2 of HC comprising SEQ ID NO: 32, and a CDR3 of HC comprising SEQ ID NO:

52.

72. Antigen-binding domain according to claim 70 or 71, characterized in that the variable region light chain domain comprises: a. a CDR1 of LC comprising SEQ ID NO: 7, a CDR2 of LC comprising SEQ ID NO: 8, and a CDR3 of LC comprising SEQ ID NO: 9; b. a CDR1 of LC comprising SEQ ID NO: 10, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 12; c. a CDR1 of LC comprising SEQ ID NO: 53, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; d. a CDR1 of LC comprising SEQ ID NO: 54, a CDR2 of LC comprising SEQ ID NO: 67, and a CDR3 of LC comprising SEQ ID NO: 77; and a CDR1 of LC comprising SEQ ID NO: 55, a CDR2 of LC comprising SEQ ID NO: 68, and a CDR3 of LC Petition 870250084408, dated 09 / 19 / 2025, p. 246 / 297 21 / 35 comprising SEQ ID NO: 78; f.a CDR1 of LC comprising SEQ ID NO: 56, a CDR2 of LC comprising SEQ ID NO: 69, and a CDR3 of LC comprising SEQ ID NO: 79; g. a CDR1 of LC comprising SEQ ID NO: 57, a CDR2 of LC comprising SEQ ID NO: 69, and a CDR3 of LC comprising SEQ ID NO: 79; h. a CDR1 of LC comprising SEQ ID NO: 58, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; i. a CDR1 of LC comprising SEQ ID NO: 59, a CDR2 of LC comprising SEQ ID NO: 70, and a CDR3 of LC comprising SEQ ID NO: 80; j. a CDR1 of LC comprising SEQ ID NO: 60, a CDR2 of LC comprising SEQ ID NO: 71, and a CDR3 of LC comprising SEQ ID NO: 81; k. a CDR1 of LC comprising SEQ ID NO: 61, a CDR2 of LC comprising SEQ ID NO: 72, and a CDR3 of LC comprising SEQ ID NO: 77; l. a CDR1 of LC comprising SEQ ID NO: 62, a CDR2 of LC comprising SEQ ID NO: 70, and a CDR3 of LC comprising SEQ ID NO: 82; m.a CDR1 of LC comprising SEQ ID NO: 10, a CDR2 of LC comprising SEQ ID NO: 73, and a CDR3 of LC comprising SEQ ID NO: 12; n. a CDR1 of LC comprising SEQ ID NO: 63, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; o. a CDR1 of LC comprising SEQ ID NO: 64, a CDR2 of LC comprising SEQ ID NO: 68, and a CDR3 of LC Petition 870250084408, dated 09 / 19 / 2025, p. 247 / 297 22 / 35 comprising SEQ ID NO: 78; p. a CDR1 of LC comprising SEQ ID NO: 65, a CDR2 of LC comprising SEQ ID NO: 74, and a CDR3 of LC comprising SEQ ID NO: 9; q. a CDR1 of LC comprising SEQ ID NO: 66, a CDR2 of LC comprising SEQ ID NO: 75, and a CDR3 of LC comprising SEQ ID NO: 9; r. a CDR1 of LC comprising SEQ ID NO: 58, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; or s.a CDR1 of LC comprising SEQ ID NO: 60, a CDR2 of LC comprising SEQ ID NO: 71, and a CDR3 of LC comprising SEQ ID NO:

83.

73. Antigen-binding domain according to any one of claims 70 to 72, characterized in that: a. the heavy chain variable region domain comprises an HC CDR1 comprising SEQ ID NO: 1, an HC CDR2 comprising SEQ ID NO: 2, and an HC CDR3 comprising SEQ ID NO: 3, and the light chain variable region domain comprises an LC CDR1 comprising SEQ ID NO: 7, an LC CDR2 comprising SEQ ID NO: 8, and an LC CDR3 comprising SEQ ID NO: 9; b. The variable region domain of heavy chain comprises a HC CDR1 comprising SEQ ID NO: 4, a HC CDR2 comprising SEQ ID NO: 5, and a HC CDR3 comprising SEQ ID NO: 6, and the variable region domain of light chain comprises a LC CDR1 comprising SEQ ID NO: 10, a LC CDR2 comprising SEQ ID NO: 11, and a LC CDR3 comprising SEQ ID NO: 12; c. the variable region domain of heavy chain comprises Petition 870250084408, dated 09 / 19 / 2025, p.248 / 297 23 / 35 includes a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 24, and a CDR3 of HC comprising SEQ ID NO: 40, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 53, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; d. The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 13, a CDR2 of HC comprising SEQ ID NO: 25, and a CDR3 of HC comprising SEQ ID NO: 41, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 54, a CDR2 of LC comprising SEQ ID NO: 67, and a CDR3 of LC comprising SEQ ID NO: 77; and.The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 14, a CDR2 of HC comprising SEQ ID NO: 26, and a CDR3 of HC comprising SEQ ID NO: 42, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 55, a CDR2 of LC comprising SEQ ID NO: 68, and a CDR3 of LC comprising SEQ ID NO: 78; f. The variable region domain of the heavy chain comprises a HC CDR1 comprising SEQ ID NO: 15, a HC CDR2 comprising SEQ ID NO: 28, and a HC CDR3 comprising SEQ ID NO: 43, and the variable region domain of the light chain comprises a LC CDR1 comprising SEQ ID NO: 56, a LC CDR2 comprising SEQ ID NO: 69, and a LC CDR3 comprising SEQ ID NO: 79; g. the variable region domain of the heavy chain comprises a HC CDR1 comprising SEQ ID NO: 15, a HC CDR2 comprising SEQ ID NO: 29, and a HC CDR3 comprising Petition 870250084408, dated 09 / 19 / 2025, p.249 / 297 24 / 35 comprises SEQ ID NO: 44, and the light chain variable region domain comprises an LC CDR1 comprising SEQ ID NO: 57, an LC CDR2 comprising SEQ ID NO: 69, and an LC CDR3 comprising SEQ ID NO: 79; h. the heavy chain variable region domain comprises an HC CDR1 comprising SEQ ID NO: 16, an HC CDR2 comprising SEQ ID NO: 30, and an HC CDR3 comprising SEQ ID NO: 45, and the light chain variable region domain comprises an LC CDR1 comprising SEQ ID NO: 58, an LC CDR2 comprising SEQ ID NO: 11, and an LC CDR3 comprising SEQ ID NO: 76; i.The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 17, a CDR2 of HC comprising SEQ ID NO: 31, and a CDR3 of HC comprising SEQ ID NO: 46, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 59, a CDR2 of LC comprising SEQ ID NO: 70, and a CDR3 of LC comprising SEQ ID NO: 80; j. The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 18, a CDR2 of HC comprising SEQ ID NO: 32, and a CDR3 of HC comprising SEQ ID NO: 47, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 60, a CDR2 of LC comprising SEQ ID NO: 71, and a CDR3 of LC comprising SEQ ID NO: 81; k.The variable region domain of the heavy chain comprises a HC CDR1 comprising SEQ ID NO: 19, a HC CDR2 comprising SEQ ID NO: 33, and a HC CDR3 comprising SEQ ID NO: 48, and the variable region domain of the light chain comprises a LC CDR1 comprising SEQ ID NO: 61, Petition 870250084408, dated 09 / 19 / 2025, page 250 / 297 25 / 35 a LC CDR2 comprising SEQ ID NO: 72, and a LC CDR3 comprising SEQ ID NO: 77; l. The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 20, a CDR2 of HC comprising SEQ ID NO: 34, and a CDR3 of HC comprising SEQ ID NO: 49, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 62, a CDR2 of LC comprising SEQ ID NO: 70, and a CDR3 of LC comprising SEQ ID NO: 82; m.The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 35, and a CDR3 of HC comprising SEQ ID NO: 50, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 10, a CDR2 of LC comprising SEQ ID NO: 73, and a CDR3 of LC comprising SEQ ID NO: 12; n. The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 4, a CDR2 of HC comprising SEQ ID NO: 5, and a CDR3 of HC comprising SEQ ID NO: 6, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 63, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; o.The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 14, a CDR2 of HC comprising SEQ ID NO: 36, and a CDR3 of HC comprising SEQ ID NO: 51, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 64, a CDR2 of LC comprising SEQ ID NO: 68, and a CDR3 of LC comprising SEQ ID NO: 78; Petition 870250084408, dated 09 / 19 / 2025, pp. 251 / 297 26 / 35 p. The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 15, a CDR2 of HC comprising SEQ ID NO: 37, and a CDR3 of HC comprising SEQ ID NO: 3, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 65, a CDR2 of LC comprising SEQ ID NO: 74, and a CDR3 of LC comprising SEQ ID NO: 9; q.The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 21, a CDR2 of HC comprising SEQ ID NO: 38, and a CDR3 of HC comprising SEQ ID NO: 3, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 66, a CDR2 of LC comprising SEQ ID NO: 75, and a CDR3 of LC comprising SEQ ID NO: 9; r. The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 22, a CDR2 of HC comprising SEQ ID NO: 39, and a CDR3 of HC comprising SEQ ID NO: 45, and a variable region of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 58, a CDR2 of LC comprising SEQ ID NO: 11, and a CDR3 of LC comprising SEQ ID NO: 76; or s.The variable region domain of the heavy chain comprises a CDR1 of HC comprising SEQ ID NO: 23, a CDR2 of HC comprising SEQ ID NO: 32, and a CDR3 of HC comprising SEQ ID NO: 52, and the variable region domain of the light chain comprises a CDR1 of LC comprising SEQ ID NO: 60, a CDR2 of LC comprising SEQ ID NO: 71, and a CDR3 of LC comprising SEQ ID NO:

83.

74. Antigen-binding domain according to any one of claims 70 to 73, characterized in that Petition 870250084408, dated 09 / 19 / 2025, p. 252 / 297 27 / 35 The variable region domain of the heavy chain comprises a sequence selected from the group consisting of SEQ ID NOS: 96, 97, 102, 104, 106, 108, 112, 114, 116, 118, 120, 122, 124, 126, 128, 132, 134, 136, 138, 140, 156, 158, 160, 162, 164, 166, 168, 170 and 172, or a sequence having at least 80%, at least 90%, or at least 95% identity therewith.

75. Antigen-binding domain according to any one of claims 70 to 74, characterized in that the variable region light chain domain comprises a sequence selected from the group consisting of SEQ ID NOS: 98, 99, 103, 105, 107, 109, 113, 115, 117, 119, 121, 122, 125, 127, 129, 131, 133, 135, 137, 139, 141, 157, 159, 161, 163, 165, 167, 169, 171 and 173, or a sequence having at least 80%, at least 90%, or at least 95% identity therewith.

76. Antigen-binding domain according to any one of claims 70 to 75, characterized in that: a. the heavy chain variable region domain comprises an amino acid sequence of SEQ ID NO: 96, and the light chain variable region domain comprises an amino acid sequence of SEQ ID NO: 98; b. the heavy chain variable region domain comprises an amino acid sequence of SEQ ID NO: 97, and the light chain variable region domain comprises an amino acid sequence of SEQ ID NO: 99; c. the heavy chain variable region domain comprises an amino acid sequence of SEQ ID NO: 102, and the light chain variable region domain comprises an amino acid sequence of SEQ ID NO: 103; d. The variable region domain of the heavy chain comprises an amino acid sequence with SEQ ID NO: 104, and in which Petition 870250084408, dated 09 / 19 / 2025, page.253 / 297 28 / 35 variable region domain of light chain comprises an amino acid sequence of SEQ ID NO: 105; e. the variable region domain of heavy chain comprises an amino acid sequence of SEQ ID NO: 106, and wherein the variable region domain of light chain comprises an amino acid sequence of SEQ ID NO: 107; f. the variable region domain of heavy chain comprises an amino acid sequence of SEQ ID NO: 108, and wherein the variable region domain of light chain comprises an amino acid sequence of SEQ ID NO: 109; g. the variable region domain of heavy chain comprises an amino acid sequence of SEQ ID NO: 112, and wherein the variable region domain of light chain comprises an amino acid sequence of SEQ ID NO: 113; h. the variable region domain of the heavy chain comprises an amino acid sequence with SEQ ID NO: 114, and wherein the variable region domain of the light chain comprises an amino acid sequence with SEQ ID NO: 115; i.the variable region domain of the heavy chain comprises an amino acid sequence with SEQ ID NO: 116, and wherein the variable region domain of the light chain comprises an amino acid sequence with SEQ ID NO: 117; j. the variable region domain of the heavy chain comprises an amino acid sequence with SEQ ID NO: 118, and wherein the variable region domain of the light chain comprises an amino acid sequence with SEQ ID NO: 119; or k. the variable region domain of the heavy chain comprises an amino acid sequence with SEQ ID NO: 120, and wherein the variable region domain of the light chain comprises an amino acid sequence with SEQ ID NO:

121. Petition 870250084408, dated 19 / 09 / 2025, pp. 254 / 297 29 / 35.

77. Antigen-binding domain according to any one of claims 70 to 76, characterized in that the antigen-binding domain comprises a Fab fragment, an F(ab%) fragment, an scFv, a scab, a dAb, a single-domain heavy chain antibody, or a single-domain light chain antibody.

78. Antibody, characterized in that it comprises the antigen-binding domain as defined in any one of claims 70 to 76.

79. Chimeric antigen receptor (CAR), characterized in that it comprises an antigen-binding domain as defined in any one of claims 70 to 76.

80. Immune cell, characterized in that it comprises the CAR as defined in claim 79.

81. Immune cell according to claim 80, characterized in that the immune cell is a T cell or a natural killer (NK) cell.

82. Antibody-drug conjugate, characterized in that it comprises (a) a first antigen-binding domain that specifically binds to a first 5T4 epitope; (b) a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and (c) a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; wherein the antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, the second antigen-binding domain comprising an scFv; and wherein the antibody-drug conjugate comprises: (a) two polypeptides comprising a heavy chain variable region domain comprising: i. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1; ii.(a) a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 2; and iii. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 3; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and (b) two polypeptides comprising a variable region light chain domain comprising: i. a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 7; ii. a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 8; and iii.a CDR3 sequence of LC comprising an amino acid sequence of SEQ ID NO: 9; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it.

83. Antibody-drug conjugate, characterized in that it comprises (a) a first antigen-binding domain that specifically binds to a first 5T4 epitope; Petition 870250084408, dated 09 / 19 / 2025, p. 256 / 297 31 / 35 (b) a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and (c) a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; wherein the antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain and the second antigen-binding domain comprising an scFv, and wherein the antibody-drug conjugate comprises: (a) two polypeptides comprising a variable region heavy chain domain comprising: i. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 4; ii.(a) a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5; and iii. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and (b) two polypeptides comprising a variable region light chain domain comprising: i. a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 10; ii. a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 11; and iii. a sequence of CDR3 files from LC comprising Petition 870250084408, dated 09 / 19 / 2025, p.257 / 297 32 / 35 amino acid sequence of SEQ ID NO: 12; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it.

84. Antibody-drug conjugate, characterized in that it comprises (a) a first antigen-binding domain that specifically binds to a first 5T4 epitope; (b) a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and (c) a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antibody; wherein the antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprises an scFv, and wherein the antibody-drug conjugate comprises: (a) two polypeptides comprising a first heavy chain variable region domain comprising: i. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1; ii.a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 2; and iii. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 3; a second heavy chain variable region domain comprising: Petition 870250084408, dated 19 / 09 / 2025, p. 258 / 297 33 / 35 i. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 4; ii. a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5; and iii. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6; and a light chain variable region domain comprising: i. a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 7; ii. a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 8; and iii.(a) a CDR3 LC sequence comprising an amino acid sequence of SEQ ID NO: 9; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and (b) two polypeptides comprising a variable region light chain domain comprising: i. a CDR1 LC sequence comprising an amino acid sequence of SEQ ID NO: 10; ii. a CDR2 LC sequence comprising an amino acid sequence of SEQ ID NO: 11; and iii. a CDR3 LC sequence comprising an amino acid sequence of SEQ ID NO: 12; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith. Petition 870250084408, dated 19 / 09 / 2025, p. 259 / 297 34 / 35.

85. Antibody-drug conjugate, characterized in that it comprises (a) a first antigen-binding domain that specifically binds to a first 5T4 epitope; (b) a second antigen-binding domain that specifically binds to a second 5T4 epitope that is not the same as the first 5T4 epitope; and (c) a chemotherapeutic agent; wherein the first antigen-binding domain is operably linked to the second antigen-binding domain; wherein the antibody-drug conjugate comprises a full-size IgG antibody comprising the first antigen-binding domain, and the second antigen-binding domain comprises an scFv, and wherein the antibody-drug conjugate comprises: (a) two polypeptides comprising a first heavy chain variable region domain comprising: i. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 1; ii.a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 2; and iii. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 3; a second heavy chain variable region domain comprising: i. a CDR1 sequence of HC comprising an amino acid sequence of SEQ ID NO: 4; ii. a CDR2 sequence of HC comprising an amino acid sequence of SEQ ID NO: 5; and iii. a CDR3 sequence of HC comprising an amino acid sequence of SEQ ID NO: 6; and a light chain variable region domain comprising: i. a CDR1 sequence of LC comprising an amino acid sequence of SEQ ID NO: 10; ii. a CDR2 sequence of LC comprising an amino acid sequence of SEQ ID NO: 11; and iii.(a) a CDR3 LC sequence comprising an amino acid sequence of SEQ ID NO: 12; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 100, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity therewith; and (b) two polypeptides comprising a variable region light chain domain comprising: i. a CDR1 LC sequence comprising an amino acid sequence of SEQ ID NO: 7; ii. a CDR2 LC sequence comprising an amino acid sequence of SEQ ID NO: 8; and iii. a CDR3 LC sequence comprising an amino acid sequence of SEQ ID NO: 9; wherein the polypeptides comprise an amino acid sequence of SEQ ID NO: 101, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity with it.

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